Ryanodine receptors (RyRs) are calcium channels located on the endo(sarco)plasmic reticulum of muscle cells and neurons. They are the largest ion channels known made up of four monomers, each 565kDa in size. Mammals have 3 different RyR isoforms, encoded by different genes, while insects express only one isoform of the receptor, which is only 46% similar (at the amino acid level) to its mammalian counterpart(s). RyRs function to regulate the release of luminal Ca2+ stores into the cell cytoplasm and play a key role in muscle excitation-contraction coupling (ECC). The plant alkaloid ryanodine, from which the receptor derives its name, has been investigated extensively as a potential pest control agent, but to date no commercial products have been identified. Recently two synthetic insecticides selectively targeting pest RyRs were introduced to the market. These compounds belong to the novel group of insecticides called diamides. In this study two insect ryanodine receptors were isolated sequenced and cloned into suitable expression vectors from economically important pests M. persicae and P. xylostella to identify protein site of interaction for the novel compounds. Both proteins were expressed in HEK 293 cells and Sf9 cells and analysed for evidence of function using ryanodine binding assays and calcium release imaging. In the case of M. persicae RyR the expression level was not sufficient to obtain any functional data. However the expression of P. xylostella RyR showed evidence of function in both HEK and Sf9 cells. Functional studies showed that expressed P. xylostella RyR can bind [3H] ryanodine and respond to various caffeine concentrations; the protein was also sensitive to both diamide compounds. DNA sequencing of RyR from field evolved diamide resistant strains of P. xylostella identified a mutation causing amino acid change G4946E. Functional analysis of modified RyR construct in Sf9 cells showed significantly reduced sensitivity to to both diamide compounds while retaining caffeine and ryanodine sensitivity comparable to the expressed WT form.

Left ventricular (LV) function is an important predictor of outcome after cardiac surgery. Severely impaired LV function (EF<20%) carries a 4-fold increase in the risk of in-hospital mortality compared to patients with EF >40%. Optimising LV function in the peri-operative setting may improve outcomes. Haemodynamic studies of permanent BiV pacing have reported a relative 25% increase in EF compared to dual-chamber right ventricular pacing. Methods: 38 patients in sinus rhythm, ejection fraction ≤35%, undergoing on-pump cardiac surgery were enrolled into the main study. All patients received temporary pacing wires attached to the right atrium, right ventricular outflow tract and left ventricle. Patients were randomly assigned to post-operative biventricular pacing or atrial-inhibited/dual-chamber right ventricular pacing. The primary endpoint was the transition from level 3 to level 2 care. The cardiac output measurements obtained using the PA catheters were compared to simultaneous measurements obtained from a FloTrac device (Edwards Lifesciences, arterial pulse-wave analysis). The measurements were compared using a Bland-Altman analysis. Results: The median duration of level 3 care was 22.0 (IQR: 16.0-66.5) hours and 37.5 (IQR: 16.3-55.0) hours in the BiV and standard pacing groups respectively (log-rank p=0.58, 95% CI: 0.43-1.61). At 18 hours, cardiac output with biventricular pacing (5.8 L/min) was 9% higher than dual chamber right ventricular pacing (5.3 L/min), ( p=0.001). Optimisation of the VV interval produced a further 4% increase in cardiac output (p=0.005). Analysis of the cardiac output measurements taken simultaneously from the PA catheter and FloTrac system yielded a bias -0.33L/min±2.2 L/min and a percentage error of 42%. Conclusions: Patients who require post-operative pacing or a prolonged haemodynamic support after surgery may benefit from optimised BiV pacing. However, for the majority of patients BiV pacing does not alter the clinical outcome compared to atrial-inhibited or dual chamber RV pacing. Although the FloTrac system is easy to use and rapidly reports changes in cardiac output, its precision requires refinement before it can be used instead of a PA catheter.

Chronic treatment of rats (to induce pulmonary hypertension, PHT) for 14 days increased cGMP-inhibited. cAMP specific phosphodiesterase (PDE3), and cGMP binding, cGMP specific phosphodiesterase (PDE5) activities in selected branches of the pulmonary artery (MacLean et al., 1997). The objective of this study was to establish the molecular basis for these changes in both animal and cell models of PHT, and also to investigate the effect the PDE3 inhibitor SKF94836, and the PDE5 inhibitor slideafil, on isolated pulmonary arteries from normoxic and hypoxic rats. It was shown that PDE3A/B gene transcription was increased in the main, first, intrapulmonary and resistance pulmonary arteries. Transcript and protein levels of PDE5A2 in the main and first branch pulmonary arteries (PAs) were also increased by chronic hypoxia. In addition, the expression of PDE3A was increased in cultured human pulmonary smooth muscle cells (hPASMC) maintained under chronic hypoxic conditions for 14 days, and this may be mediated via a protein kinase A-dependent mechanism. The treatment of cells with 8-Br-cAMP mimicked chronic hypoxia, inducing increased PDE3A expression, while treatment with the protein kinase A selective inhibitor, H8 peptide, abolished chronic hypoxia-induced expression of PDE3A. Finally, the treatment of cultured hPASMC, with the inhibitor of NF-kB degradation Tosyl-Leucyl-Chloro-Ketone (TLCK, 100mM), substantially reduced PDE5 transcript levels, suggesting a role for this transcription factor in the regulation of PDE5 gene expression. This is of interest because NF-kB is activated by hypoxia (Muraoka et al. 2000, Aziz et al., 1997). Taken together, our results show that phenotypic changes in the expression of PDE3 and PDE5 might provide an explanation for some of the changes in vascular reactivity of pulmonary vessels from rats with PHT. Both SKF94836 (PDE3 inhibitor), and sildenafil (PDE5 inhibitor) were effective in producing a concentration-dependent relaxation in isolated PAs.

This thesis has developed to explore a specific intervention in a core context. That context is the transition of stroke from hospital to home and from acute illnesses to chronic disease. This includes the change from a rehabilitation focus on the physical effects and complications of stroke (during in-patient stroke unit care) to the psychological, emotional and social consequences of stroke as well as the risk of recurrence. Specifically it focuses on an intervention in two key problem areas. The first is the risk of stroke or transient ischaemic attack (TIA) recurrence and risk factor modification through lifestyle change. The second is the area of psychosocial problems post stroke. Both these areas may be addressed by a single intervention, and it is that potential intervention that is evaluated in detail in this thesis. Other problem areas such as functional recovery and interventions to affect this are set in context, but not specifically covered here. Chapter One highlights the association in the literature between the well documented social and psychological consequences of stroke and longer term health outcomes for patients. We can see from the literature that there is a strong association between depression and worse outcomes in terms of rehabilitation, reduced cognitive functioning and increased mortality. In addition patients with poor social support or poor family functioning are recognised to have a longer length of hospital stay and poorer rehabilitation profile. Patients who have a poor understanding of their illness are less likely to comply with treatment advice or re-attend for further treatment. There is therefore a setting for evaluating an intervention that might seek to impact the emotional, informational and social needs of patients post stroke. Chapter Two describes a randomised controlled trial of a Stroke Nurse Specialist intervention in a behaviour modification programme. This trial was intended to address the risk of Transient Ischaemic Attack (TIA) or Stroke recurrence by aiming to improve the information needs of post stroke and TIA patients, hoping to improve their compliance, lifestyle modification and ultimately risk factor control. The primary outcome was the proportion of patients who achieved control of all their modifiable risk factors (e.g. smoking, hypertension, diabetes and hypercholesterolaemia) according to predetermined criteria. No significant difference was seen between the groups for the primary outcome (proportion achieving risk factor control: Experiment 46.4% Vs Control 41.7%, p=0.34). Differences were seen between the groups in the reduction in systolic blood pressure (Experiment -9.2mmHg, SD 23.3 Vs Control -1.0mmHg, SD 22.4, p=0.04). In addition patients in the experimental group were more likely to express satisfaction with aspects of liaison and information provision. Chapter Three evaluates the effects of the short term behaviour modification intervention (detailed in Chapter Two) at over three years after initial enrolment. Rates of follow up of the initial cohort were lower than the initial study (50% compared to 94%). No significant difference exists at three years between the intervention and control groups for the primary outcome of risk factor control. Differences were observed between the groups for the rates of admission to nursing homes (Experiment 0 Vs Control 5, p=0.02), however the small size of this follow up sample limits the conclusions that can be drawn from this result. Chapter Four attempts to set the randomised controlled trial evaluated in Chapters Two and Three in the context of other outpatient rehabilitation interventions and tries to establish if there is comparability between the interventions and even combinability for subsequent meta-analysis. This process identifies several core themes: • Physical fitness training after stroke, • Occupational therapy after stroke, • Multidisciplinary rehabilitation post stroke, • Information provision and education post stroke and • Psychological and social support. In addition, several trials targeting intervention aimed at carers only were identified. Chapter Five describes a systematic review and meta-analysis of Stroke Liaison Worker trials – that is trials that evaluated a healthcare worker or volunteer who provided social support, information and liaison with the patient after discharge. This includes the trial described in Chapter Two. Individual patient data meta-analysis was conducted of 16 trials evaluating 18 interventions. Meta-analysis did not demonstrate any benefit of Stroke Liaison Workers compared to usual care for the primary outcomes of subjective health status or extended activities of daily living. In addition there was no benefit from Stroke Liaison Worker on the outcomes of death, institutionalisation, mental health or dependence. Patients were more satisfied that someone had really listened to them. Carers were more satisfied that they had received enough information about the causes of stroke, that they had enough information about recovery, that someone had really listened, and that they did not feel neglected. Subgroup analysis by patient dependence at recruitment revealed that patients with mild to moderate dependence had reduced dependence in the intervention group (OR 0.60, 0.44 – 0.83, p=0.002) as well as a reduction in death or dependence (OR 0.55, 0.39 – 0.78, p=0.0008). In Chapter Six I was keen to evaluate whether the interventions in the literature and the framework for combining and evaluating them could be mapped onto existing services in Scotland. This was done through a questionnaire of the Scottish Stroke Nurses Forum. This identified 58 Stroke Liaison Workers from around Scotland who identified themselves as providing the services described using the review criteria in Chapter Five. These nurses identified that their commonest requests for help relate to psychological or emotional issues. 62% of respondents believed that their role was effective for all their patients. In conclusion, Stroke Liaison Workers result in greater satisfaction with certain aspects of service provision but do not appear to result in changes to patient subjective health, extended ADL or carer subjective health. Subgroup analysis suggests that patients with mild to moderate dependence may benefit. Overall there does not appear to be evidence of effectiveness for this complex intervention when applied to all patients or carers.

Patients with end stage renal disease (ESRD) have a 20-100 fold risk of premature cardiovascular death compared to age matched controls from the general population. These patients have many ‘conventional’ cardiovascular risk factors such as diabetes, ischaemic heart disease, hypertension, cigarette smoking and hyperlipidaemia. However, the relationship between the presence of these risk factors and cardiovascular outcomes is less clear in ESRD than in the general population. In the cases of hyperlipidaemia and hypertension a paradoxical relationship has been demonstrated where lower cholesterol or blood pressure is associated with an increased risk of cardiovascular events. One factor previously demonstrated to be associated with poor prognosis is the presence of uraemic cardiomyopathy, found in approximately 70% of ESRD patients at initiation of dialysis therapy, usually defined echocardiographically as the presence of left ventricular (LV) abnormalities, including left ventricular hypertrophy (LVH), LV dilatation and LV systolic dysfunction. However, echocardiography makes assumptions regarding LV geometry, which is frequently distorted in patients with ESRD. Furthermore any errors in measurements are amplified by the changes in hydration status which occur during the dialysis cycle, leading to changes in LV chamber dimensions. For these reasons, cardiac magnetic resonance imaging (CMR), by providing high fidelity measurements, potentially offers a ‘volume independent’ method of quantifying LV dimensions. Furthermore, by using gadolinium based contrast agents, tissue abnormalities particularly myocardial fibrosis, indicated by late gadolinium enhancement (LGE) may by identified. The work contained in this thesis examines the relationship between cardiac dimensions, as defined by CMR and cardiovascular risk factors (both conventional and specific to uraemia). In a study of 145 patients with ESRD using CMR with gadolinium, two specific pathological processes were demonstrated. First, the presence of subendocardial LGE indicating previous myocardial infarction was associated with the presence of conventional cardiovascular risk factors such as previous ischaemic heart disease and diabetes. Patients with subendocardial LGE frequently had LV systolic dysfunction. Second, diffuse LGE, representing fibrosis throughout the LV wall was identified in patients with LVH. This was an unexpected finding and appears specific to uraemia. Using CMR, isolated LV dilatation was rare. These findings suggest that in uraemia two forms of cardiomyopathy exist- LV systolic dysfunction due to underling myocardial ischaemia and LVH which is a true ‘uraemic cardiomyopathy’ associated with diffuse myocardial fibrosis. Attempts were made to reassess the relationship between CMR and echocardiographic measures of cardiac dimensions. In keeping with a previous study, it was demonstrated that M-mode echocardiography overestimates LV mass compared to CMR in this population. Thus, CMR may be used to optimise echocardiographic formulae to calculate LV mass. Furthermore, it appeared that either by echocardiography or by CMR the chief determinant of LVH in this population was blood pressure, in particular systolic blood pressure. This has implications for treatment as recent studies aimed at correcting anaemia, previously associated with LVH, either to reduce LV mass or to improve survival, have generally demonstrated increased cardiovascular events with higher haemoglobin. Therefore, if LV mass is a goal of treatment, attempts should be made to reduce blood pressure further in this population. The patients studied in these investigations were candidates for renal transplantation, the definitive treatment for chronic renal failure. Cardiovascular disease is the leading cause of death both in patients on the renal transplant list, as well as post successful transplantation. There is a great deal of interest in identifying patients at high cardiovascular risk, to allow strategies to be adopted to minimise this risk, frequently by undertaking invasive investigation such as coronary angiography. In a survival study of 300 potential renal transplant recipients, factors associated with increased risk of mortality were increased age, ischaemic heart disease whilst receipt of a renal transplant was protective. Although the presence of LGE was associated with poorer outcome, this finding was not independent of other variables. One interesting finding was that patients with greater exercise tolerance, measured objectively using the full Bruce exercise test had better outcomes. This observation represents a simple pragmatic method to risk-stratify such patients. A study using the biomarker brain natriuretic peptide (BNP) a peptide released from the LV in response to stretch and hypertrophy, in 114 patients, demonstrated that whilst BNP has potential as a diagnostic tool for the presence of uraemic cardiomyopathy, in particular LVH, this peptide added little prognostic value. As familiarity with CMR techniques developed, it became clear that vascular function could be investigated with this imaging modality. Previous studies using alternative measures of vascular function have suggested that arterial stiffness is an important predictor of long term outcome in patients with ESRD. A study of 147 uraemic patients using aortic distensibilty and aortic volumetric arterial strain as CMR measures of aortic stiffness demonstrated that both these parameters were associated with an increased risk of cardiovascular events and mortality. To date there do not appear to be any similar outcome studies using these measures, although a number of authors have noted an association between aortic distensibilty and cardiovascular risk factors. These factors may represent potential targets for therapy aimed at reduction of cardiovascular risk in patients with ESRD. One unfortunate development during the period during which these studies were undertaken, was the emergence of a link between exposure to gadolinium based contrast agents and nephrogenic systemic fibrosis (NSF), a potentially life threatening skin disorder in patients with advanced renal failure. This finding lead to the cessation of contrast CMR studies. A retrospective investigation of factors present in patients in North Glasgow affected by NSF, confirmed that patients with NSF were more likely to have undergone contrast based imaging than unaffected patients, frequently undergoing multiple scans, with high doses of gadodiamide used. Until this issue is clarified, future scans using these agents in this population should be undertaken with caution. These studies have characterised for the first time the relationship between both uraemic cardiomyopathy and uraemic arterial stiffness and both cardiovascular risk factors and long term outcome. CMR measures of cardiac dimensions and vascular function represent future targets for interventions aimed at reducing cardiovascular risk in patients with advanced renal failure.

General practitioners (GPs) and their teams in the United Kingdom (UK) are encouraged to identify and analyse significant health care events. Additionally, there is an expectation that specific significant events should be notified to reporting and learning systems where these exist. Policy initiatives – such as clinical governance, GP appraisal and the new General Medical Services (nGMS) contract - attempt to ensure that significant event analysis (SEA) is a frequent educational activity for GP teams. The presumption from policymakers and healthcare authorities is that GP teams are demonstrating a commitment to reflect on, learn from and resolve issues which impact on the quality and safety of patient care. However, there is minimal evidence to support these assumptions while there is no uniform mechanism to ensure consistency in the quality assurance of SEA reports. One potential method of enhancing both the learning from and the quality of SEA is through peer review. In the west of Scotland an educational model to facilitate the peer review of SEA reports has existed since 1998. However, knowledge and understanding of the role and impact of this process are limited. With the potential of peer review of SEA to contribute to GP appraisal and the nGMS contract, there was a need to develop a more evidence-based approach to the peer review of SEA. The main aims of this thesis therefore are: • To identify and explore the issues involved if the identification, analysis and reporting of significant events are to be associated with quality improvement in general practice. • To investigate whether a peer feedback model can enhance the value of SEA so that its potential as a reflective learning technique can be maximised within the current educational and contractual requirements for GPs. To achieve these aims a series of mixed-methods research studies was undertaken: To examine attitudes to the identification and reporting of significant events a postal questionnaire survey of 617 GP principals in NHS Greater Glasgow was undertaken. Of the 466 (76%) individuals who responded, 81 (18%) agreed that the reporting of such events should be mandatory while 317 (73%) indicated that they would be selective in what they notified to a potential reporting system. Any system was likely to be limited by a difficulty for many GPs (41%) in determining when an event was ‘significant.’ To examine levels of agreement on the grading, analysis and reporting of standardised significant events scenarios between different west of Scotland GP groups (e.g. GP appraisers, GP registrar trainers, SEA peer reviewers) a further postal questionnaire survey was conducted. 122 GPs (77%) responded. No difference was found between the groups in the grading severity of significant events scenarios (range of p values = 0.30-0.79). Increased grading severity was linked to the willingness of each group to analyse and report that event (p<0.05). The strong levels of agreement suggest that GPs can prioritise relevant significant events for formal analysis and reporting. To identify the range of patient safety issues addressed, learning needs raised and actions taken by GP teams, a sample of 191 SEA reports submitted to the west of Scotland peer review model were subjected to content analysis. 48 (25%) described incidents in which patients were harmed. A further 109 reports (57%) outlined circumstances which had the potential to cause patient harm. Learning opportunities were identified in 182 reports (95%) but were often non-specific professional issues such as general diagnosis and management of patients or communication issues within the practice team. 154 (80%) described actions taken to improve practice systems or professional behaviour. Overall, the study provided some proxy evidence of the potential of SEA to improve healthcare quality and safety. To improve the quality of SEA peer review a more detailed instrument was developed and tested for aspects of its validity and reliability. Content validity was quantified by application of a content validity index and was demonstrated, with at least 8 out of 10 experts endorsing all 10 items of the proposed instrument. Reliability testing involved numerical marking exercises of 20 SEA reports by 20 trained SEA peer reviewers. Generalisability (G) theory was used to investigate the ability of the instrument to discriminate among SEA reports. The overall instrument G co-efficient was moderate to good (G=0.73), indicating that it can provide consistent information on the standard achieved by individual reports. There was moderate inter-rater reliability (G=0.64) when four raters were used to judge SEA quality. After further training of reviewers, inter-rater reliability improved to G>0.8, with a decision study indicating that two reviewers analysing the same report would give the model sufficient reliability for the purposes of formative assessment. In a pilot study to examine the potential of NHS clinical audit specialists to give feedback on SEA reports using the updated review instrument, a comparison of the numerical grading given to reports by this group and established peer reviewers was undertaken. Both groups gave similar feedback scores when judging the reports (p=0.14), implying that audit specialists could potentially support this system. To investigate the acceptability and educational impact associated with a peer reviewed SEA report, semi-structured interviews were undertaken with nine GPs who had participated in the model. The findings suggested that external peer feedback is acceptable to participants and enhanced the appraisal process. This feedback resulted in the imparting of technical knowledge on how to analyse significant events. Suggestions to enhance the educational gain from the process were given, such as prompting reviewers to offer advice on how they would address the specific significant event described. There was disagreement over whether this type of feedback could or should be used as supporting evidence of the quality of doctors’ work to educational and regulatory authorities. In a focus group study to explore the experiences of GP peer reviewers it was found that acting as a reviewer was perceived to be an important professional duty. Consensus on the value of feedback in improving SEA attempts by colleagues was apparent but there was disagreement and discomfort about making a “satisfactory” or an “unsatisfactory” judgement. Some concern was expressed about professional and legal obligations to colleagues and to patients seriously harmed as a result of significant events. Regular training of peer reviewers was thought to be integral to maintaining their skills. The findings presented contribute to the limited evidence on the analysis and reporting of significant events in UK general practice. Additionally, aspects of the utility of the peer review model outlined were investigated and support its potential to enhance the application of SEA. The issues identified and the interpretation of findings could inform GPs, professional bodies and healthcare organisations of some of the strengths and limitations of SEA and the aligned educational peer review model.

This thesis examines the issue of clinical involvement in the commissioning process within the NUS internal market. It is based on an applied research project undertaken across the purchaser provider divide in one NHS region, during the 1994- 95 annual commissioning cycle. Six District Health Authorities and thirty NUS Trusts in South East Thames took part in the research, which was commissioned by the South East Commissioning Development Network. The purpose of the research was to support the development of the NHS commissioning function across the region. Specific research objectives included assessing the levels of clinical involvement in commissioning at a local level and exploring how the provider clinicians experienced the commissioning and contracting process. The reasons why health authority Chief Executives and Directors of Public Health wished to address this issue were also explored. The research used both qualitative and quantitative approaches to data-collection and analysis. Indepth, fact-to-face interviews with 10 health authority Chief Executives and Directors of Public Health were followed by a postal survey of 325 clinical directors and similar lead clinicians. The postal survey achieved a 75% response rate. Interviews with health authority Chief Executives and Directors of Public Health found overwhelming support for involving local clinicians in the commissioning process, but a wide diversity in the reasons for this. However, on analysis of the data,a number of common themes emerged. These included the need to access clinical advice, to influence clincial behaviour, to ensure contracts are deliverable and to achieve shared ownership of change. Interviews also highlighted the complexity of the commissioning process, the lack of clarity over the purpose of commissioning, and the shortage of appropriates kills within commissioning authorities. These issues were being made more difficult by a fragmentation of relationships resulting from the introduction of the internal market, and constant organisational changes. The survey of provider clinicians revealed that less than a quarter of respondents had frequent contact with their main commissioners, and only one third felt they had a shared vision for the future of their services. Clinicians were particularly concerned that their commissioners did not understand what they were purchasing, especially in terms of clinical issues, patient need and resource constraints. Where respondents had been involved, it was mostly at the contracting stage of the annual commissioning cycle, and most felt this was inadequate. They felt their input into more strategic areas, such as agreeing service changes and developments, were more important than contract setting, negotiating and monitoring. Clinicians had mixed feelings about the process, with those who reported more frequent direct contact with their main commissioners appearing more positive. Overall, there was strong support for increasing levels of clinical involvement in commissioning, and evidence of considerable scope for improving the relationship between health authority commissioning teams and lead clinicians in the service providers. Health authority purchasing during this period is an under-researched area, and this study contributes a detailed analysis of one aspect of the workings of the internal market in one NHS region during the mid 1990s. As a case study in policy analysis, this thesis offers insights into the policy process within the UK health care system, and the ways in which this operated within the changing policy arena created by the introduction of the internal market following the Government White Paper, Working for Patients.

The thesis agrees that there can be interpreted within conscious life, the influence of the past. The past can influence the intersubjective style of an ego, a person in some of their relations with others. But Freud held an unclear position on how to interpret 'unconscious intentionality'. He preferred theory about senses that never appear and natural scientific science. It is argued that concepts such as transference, countertransference and unconscious communication should be contextualised within intersubjectivity in the strong sense of a potential manifold of interpretable perspectives on any single cultural object. The answer is to show that Freud's key ideas are situated within metaphysical commitments to natural science and material cause overall in an unclear relation to conscious psychological life. Husserl's apriori analysis of intersubjectivity is argued to explain any psychological event in relation to the past and the current therapeutic situation. Consequently, Freud's key ideas need to be abandoned in preference for a rationalisation about meaning, empathy and intersubjectivity as more adequate explanations of the conditions for the psychological meaningfulness of any psychological cultural object.

Visual crowding is a phenomenon in which the identification of visual stimuli is impaired by nearby directions. it occurs both for simple stimuli (oriented lines) and for more complex forms. The literature on crowding is reviewed, along with relevant literature on visual search and stimulus salience. Experiments are reported to test the idea that visually salient stimuli can escape, in part from crowding. The salience of stimuli was manipulated by varying their motion direction, colour, or temporal frequency relative to dis tractors. Salience was also measured independently of crowding using the pop out paradigm in visual search. Results showed that stimuli independently defined as salient did escape, in part, from crowding. A following experiment attempted to see whether the same would be true for the subjective colours experienced by synaesthetes.

The current “obesity epidemic” is a global concern for governments and healthcare organisations. Obesity is seen as a medical problem of excess body weight which can be resolved through interventions to encourage weight loss, most particularly diet and exercise regimes. Much existing sociological work focuses on moral understandings of obesity as a perceived symbol of individual greed and laziness in a culture that prioritises self-control and effort. This neglects the ways in which the condition is actively discussed and managed in relevant settings such as medical encounters. This thesis addresses this research gap by analysing talk during obesity-related medical consultations. Talk is central to all medical encounters and has particular resonance in treatments for obesity where most interventions are carried out by the patient away from the medical gaze. Patients must report on their treatment behaviours in ways that enable practitioners to evaluate them and offer further relevant advice. Talk is not only a means through which treatment is delivered but a form of treatment itself. Fieldwork took place in two UK NHS outpatient clinics specialising in weight loss treatment for obese patients. A sample of 18 patients and 1 doctor consented to have their consultations video-recorded over a period of 9 months. This resulted in 39 recorded interactions which were analysed according to the principles of Conversation Analysis (CA) to identify recurring patterns of interaction. The thesis describes how talk between doctor and patient functions to achieve certain tasks. In particular, it analyses how the specific institutional setting shapes and is shaped by talk. A dominant theme is that clinic interactions frequently invoke normative issues concerning knowledge, responsibility and effort. These issues are consistent with moral dynamics perceived to surround the condition of obesity and patient responsibilities. Doctor and patient collaboratively construct obesity as a moral issue. This has consequences for the conduct of the consultation. The findings extend existing CA knowledge on medical interactions and demonstrate the utility of an interactional approach to the sociological study of obesity. They also have relevance to healthcare policy and practice.