The broad aim of this thesis on ‘Health Economic aspects in the management of Chronic Obstructive Pulmonary Disease’ (COPD) was to study the natural history of the disease in order to inform the conceptualisation and development of a new economic model. Existing economic evaluations for COPD were critiqued and information on the natural history of the disease gathered though literature searches and analyses of two large datasets, a COPD randomised controlled trial called TORCH and a general population observational dataset called the Renfrew/Paisley (MIDSPAN) study. Particular attention was paid to identifying the COPD population using different diagnostic criteria. The elicitation of utility estimates under a number of circumstances was considered. A regression based prediction model was conceptualised and developed. Significant contributions of this thesis include, but are not limited to: a NICE COPD cohort were identified who were found to be at higher risk of all-cause and COPD mortality than a GOLD defined cohort; a mapping equation was successfully developed that predicts the EQ-5D from the SGRQ; and an entirely new concept for modelling COPD was developed that uses a series of regression equations to predict cost and effect based on lung function, symptoms and exacerbations and weighted by survival probability in order to generate a model with one arm representing current treatment and a second arm representing a comparator treatment. The thesis successfully combined information gathered throughout the period of research on the natural history of COPD with treatment effects in a novel way in order to conceptualise and develop a new economic model for COPD.

Introduction: The consequences of sustaining a head injury (HI) are varied. Recent research has begun to explore the experience of HI on identity which can, in turn, affect wellbeing. The move into a care home is also associated with changes to identity and wellbeing. Arguably changes to social identity (a form of identity based on membership to social groups) are particularly salient in this setting. Despite this, there have been no studies examining social identity in individuals with severe HI who reside in care homes. Aims: This exploratory study examines the perceptions of adults with severe HI residing in care homes, their relatives and care staff using a social identity framework. Methods: Eight participants from three group perspectives took part in this study (three adults with severe head injuries, two relatives and three staff carers) comprising two participant triads and one participant dyad. Semi-structured, open-ended interviews were completed and recorded with each participant on an individual basis. Transcripts were analysed using Interpretative Phenomenological Analysis. Results: Three superordinate themes were found: doing as normality, HI as separate from the individual and being a child and an adult. Discussion: Social identity processes of pre-injury identity loss and the acquisition of new social identities relating to the HI and being a resident in a care home are discussed. HI and the care home environment lead to perceptions of the PPs as part of a homogenous group which result in stigmatising interactions. The role of socially meaningful behaviour in mediating perceptions of the PPs is raised as well as the need to acknowledge issues relating to insight and current ability. It is unclear based on the results of this study whether needs relating to identity are met within care homes. Conclusion: The importance of taking an individual approach to explore meaningful social activity for the PPs and the recognition of the importance of this in relatives and carers is highlighted. Further research into interventions for this population and care staff is recommended.

This thesis explored aspects of the urban-rural interface within a densely populated, deprived housing scheme located on a remote, rural island lying off the north west coast of Scotland. The thesis had two aims, the first related to health, health inequality and aspects of neighbourhood and from this exploration a second aim emerged that focused in detail on the effects of rurality and religion as significant cultural influences that determined the nature of health and social environment. The Cearns housing area of Stornoway on the Isle of Lewis is reminiscent of a mainland urban scheme in terms of housing design and layout with units spaced around a series of pedestrianised courts with little green space. Significantly, most tenants, both well-established and recent, have their origins in rural Lewis, bringing with them a number of rural beliefs and behaviours. An in-depth qualitative study was carried out through individual interviews (N=55) and Cattell's social network typology was applied to inform interpretation of the nature of the social infrastructure. The main findings demonstrated the existence of 'traditional', 'socially excluded' and 'solidaristic' networks from which a strong sense of island identity, described as 'hebridean', emerged. In marked contrast to many urban areas, crime and vandalism levels were low, the housing stock was well maintained and the area was described by residents as friendly and close-knit. Hebridean communities are rural in nature, the Cearns being an anomaly, yet it shared with neighbouring villages close familial and other connections as most residents either know, or know of, their neighbours. Rurality and remoteness reinforced a 'can-do' self help culture where friendliness and co-operation is expected and this can be related to Freudenberg's notion of the 'density of acquaintanceship'. This study demonstrated that residents, irrespective of age or gender, have this view of the world, either from personal experience or through the rural upbringing of their parents and that either way a particular range of attitudes and behaviours has come with them to the Cearns. In addition to themes associated with rurality, findings from this thesis demonstrated the effect of religion at the level of the individual in terms of social support, as well as at community level in relation to social cohesion, identity and social control. Communities on the Isle of Lewis are distinctive and possibly unique within the UK in their continued adherence to the biblically strict Presbyterian religion, apparent through high levels of church attendance and strict Sabbath observance. Use of Social Identity Theory with its understanding of in-groups and out-groups provided a framework for an analysis of the interface of religion with social cohesion. The study concluded that these remote, close-knit, Gaelic-speaking, religious communities are amongst the most distinctive in the UK and that the methodology and findings of this study would have relevance in studies of similar communities elsewhere, notably within the hitherto under-researched rural communities of the Western Isles.

This thesis deals with the quantitative analysis of multiple drugs in the neonate, in blood and in meconium as an alternative biological specimen in forensic toxicology and is also concerned with the dangers of transmission of drugs used and abused by the mother to the foetus and neonate. The aims of the work were to investigate methods for performing a full drug screen on small amounts of biological specimen and to carry out a survey of illicit drug use during pregnancy in the Glasgow area. Following brief overviews of toxicology and the main problems facing the paediatric toxicologist, the development of analytical toxicology procedures to help to overcome them is summarised along with a more detailed examination of solid phase extraction (SPE) - theory, advantages and applications to biological samples. The initial experimental work established the feasibility of performing a full drug screen on small samples of blood such as those obtained from neonates, having a volume of 1-2ml. This used a single SPE cartridge for the extraction of a mixture of acidic and basic drugs followed by end-step analysis with enzyme immunoassay (ELA) and gas chromatography-mass spectrometry (GC/MS). Representative drugs from each group were selected for evaluation purposes: butobarbitone, amylobarbitone, methaqualone, primidone, and phenytoin drugs for the acidic drug group and cocaine, ecgonine methyl ester, morphine, diazepam, and desmethyldiazepam for the basic drug group. These were chosen as examples of drugs commonly used in the UK. Four analytes (morphine, methadone, cocaine and benzoylecgonine) were used to compare two different SPE cartridges, Bond Elut Certify® and Abselut®, which can be used to extract both acidic and basic drugs. The comparison involved four parameters: analyte recovery, lower limits of detection, presence of interferences in the extracts and analysis time required by each. Recoveries were in the range 60-100% and lower limits of detection were in the range 1-25 ng/ml and it was assessed that Bond Elut columns were better than Abselut columns.

Patterns of food use and of social support and alliance are significant for the constitution of boundaries between religious and ethnic groups and the status hierarchies within them. Food and social support are also significant for health. In the case of British Asian communities, control of food intake has been identified as the key to overcoming their current epidemic of heart disease. Level of stress and social support have also been thought important for understanding levels of psychological distress among British Asians. The present study focuses on young British Asian women with ancestry in the Indian subcontinent, their patterns of food use and social support and how their choice of cultural strategies affects the likelihood of change to these patterns. The rationale for concentrating upon young women is twofold. First, middle aged women appear to suffer from a number of health disadvantages, including aspects of coronary risk and psychological distress. By focusing on a younger generation of women, factors involved in the biographical development of these problems might be ascertainable. Second, in terms of the sociology of ethnic boundaries, young women are in a pivotal position with regard of the continuation of the culture, occupying a role as daughters of migrants on the one hand, and as the first generation of British role models for British Asian children on the other. Comparison with the majority ethnic group is treated as a question about how respondents view with similarities and differences between themselves and the general population. The study addresses a range of research questions from health-related issues at one extreme to issues about the social construction of ethnic groups at the other. The first group of questions concerns the role that health plays in food choice: how health is conceptualised, how far folk ideas (possibly) deriving from biomedical, Unani and Ayurvedic conceptualisations are integrated with one another, and in what social contexts health concerns are overridden by the symbolism of ethnic identity.

This thesis examines the hypothesis of cognitive polyphasia proposed by Serge Moscovici in La Psychanalyse, son Image et son Public (1961/1976). Despite its intuitive appeal, the hypothesis remains largely unexplored. This research is an attempt at understanding better the operations of cognitive polyphasia, in particular, at the level of social individuals who have to make sense of the world around them. The hypothesis of cognitive polyphasia is empirically examined through the controversy that surrounded the MMR vaccination programme in the UK between 1998 and 2005. The review of literature proposes a typology of cognitive polyphasia through an examination of empirical studies done by social representations theorists. A theoretical framework for the operationalisation of cognitive polyphasia is then proposed. This includes some elements of social cognition. The methodology chapter presents and discusses the specific methods used in this work, that is, expert interviews with health professionals and media representatives, media analysis of newspaper articles, focus groups and individual interviews with mothers of children of vaccination age. The analysis and findings of this empirical work are then presented in the results chapters focusing on their implications for our understanding of cognitive polyphasia at both the collective and the individual levels. A key finding of this study is the identification of a number of exemplars characteristic of different ways of sense making and of different ways of engaging into cognitive polyphasia. In particular, the study distinguishes between non- and polyphasic groups, that is, between people who have relied exclusively on scientific or narrative types of knowledge versus those who used a combination of types of knowledge to make sense of the MMR controversy. The theoretical implications of this work and the practical lessons that can be drawn from the public�s reactions when faced with scientific controversies are discussed in the conclusion chapter.

This thesis is concerned with economic evaluation in the primary prevention of cardiovascular disease. Policymakers are increasingly focussed on reducing the health and economic burden of CVD and to reduce health inequalities. However, the approach to primary prevention suffers from fundamental weaknesses that this research intends to help address. There is general lack of effectiveness and cost effectiveness evidence underpinning current primary prevention interventions. First, there is a policy impetus towards mass screening strategies to target individuals at high risk of developing CVD when more focussed approaches may be more cost effective. Second, clinicians prioritise individuals on the basis of 10-year risk scores, which are strongly driven by age, and not the potential benefits (or costs) from treatment. Third, targeted and population interventions are often still treated as competing approaches, whereas the key issue is how they might best combine. The key premise of this thesis is that the aims of primary prevention are the avoidance of premature morbidity, mortality and to close health inequalities - subject to a budget constraint. A CVD Policy Model was created using the same nine risk factors as used in the ASSIGN 10-year risk score, currently used in clinical practice in Scotland, to estimate life expectancy, quality adjusted life expectancy and lifetime hospital costs. This model can be employed to estimate the cost effectiveness of interventions and the impact on health inequalities. The model performed well in a comprehensive validation process in terms of face validity, internal validity, and external validity. Life expectancy predictions were re-calibrated to contemporary lifetables. This generic modelling approach (i.e. using a wide range of inputs and producing a wide range of outputs) is intended to avoid the need to build bespoke models for different interventions aimed at particular risk factors or to produce particular outputs. In application, the CVD Policy Model is intended to assist clinicians and policymakers to develop a more coherent approach to primary prevention, namely: to design more efficient screening strategies; prioritise individuals for intervention on the basis of potential benefit (rather than risk); and to assess the impact of both individually targeted and population interventions on a consistent basis. Using the model in these ways may enable primary prevention approaches to be more consistent with guidelines from health sector reimbursement agencies, which may result in a more efficient use of scarce resources.

The general subject area of research considered in this thesis is population level epidemic modelling of infectious diseases, with specific application to the problems of model indeterminacy and systems that include processes associated with maternally acquired immunity. The work presents the derivation and analysis of a lumped systems model framework to study the influence of maternal antibodies on the population dynamics of infection among neonate and young infant age classes. The proposed models are defined by sets of ordinary and partial differential equations that describe the variation of distinct states in the natural history of infection with respect to time and/or age. The model framework is extended to explore the potential population level outcomes and consequences of mass maternal immunisation: an emerging targeted vaccine strategy that utilises the active transfer of neutralising antibodies during pregnancy in order to supplement neonatal immunity during the first few months of life. A qualitative analysis of these models has highlighted the importance of interaction with early childhood targeted vaccination campaigns, the potential to invoke transient epidemic behaviour and the prospective advantages of seasonal administration. The work considers the implications of structural identifiability, indistinguishability and formal sensitivity analyses on a number of fundamental model structures within the proposed framework. These methods are used to establish whether a postulated model structure, or the individual parameters within a known structure, are uniquely determinable from a given set of empirical observations. The main epidemiological measures available for the validation of epidemic models are inherently based on records of clinical disease or age serological surveys, which are not explicitly representative of infection and provide a very limited observation of the full system state. The analyses suggest that these issues give rise to problems of indeterminacy even in the most simple models, such that certain system characteristics cannot be uniquely estimated from available data.

Zoonotic visceral leishmaniasis (ZVL) is a fatal disease caused by the sandfly-borne intracellular protozoan parasite Leishmania infantum, and vaccine development in the reservoir host (the domestic dog) is a current research priority. The aims of this study were (1) to conduct safety and immunogenicity trials of two candidate vaccines in dogs, and (2) to compare and demonstrate the utility of immunological and molecular tools for measurement of vaccine efficacy in naturally exposed dogs. DNA/ modified vaccinia virus Ankara (MVA) prime/boost canine vaccines expressing the Leishmania proteins TRYP and LACK were safe, and elicited a type-1 cytokine response, in vivo delayed-type hypersensitivity and IgG2 class responses, consistent with superior protective immunogenicity of TRYP over LACK. However, inconsistent associations were found between progressive disease in infected dogs and IgG class levels, prompting caution in use of the latter as a proxy for protective immunogenicity. Specific serological responses in vaccinated dogs did not cross-react with an unrelated diagnostic antigen rK39, and responses to crude parasite antigen (CLA) were minimal, enabling serological detection of infection incidence in vaccinated dogs. Particularly in early stage infection, CLA ELISA was more sensitive than rK39 ELISA and an rK39-based rapid diagnostic test, though rK39 serology was sensitive for diagnosis of symptomatic clinical cases. A commercially available PCR kit incorporating a rapid oligochromatographic detection step was tested for the first time in dogs, and proved highly sensitive for detection of ZVL infection in bone marrow, comparable to existing nested PCR methods. Molecular methods were investigated as proxy measures to replace labour-intensive xenodiagnosis for detection of the infectiousness of dogs to biting sand flies. Conventional and real-time PCR of tissues from naturally infected dogs were sensitive tests to identify infectiousness, but showed low to moderate specificity. Recommendations are made to improve the application of molecular methods as proxy measures of infectiousness and hence vaccine efficacy.

In this thesis several problems concerning the stochastic modelling of emerging infections are considered. Mathematical modelling is often the only available method of predicting the extent of an emerging disease and assessing proposed control measures, as there may be little or no available data on previous outbreaks. Only stochastic models capture the inherent randomness in disease transmission observed in real-life outbreaks, which can strongly influence the outcome of an emerging epidemic because case numbers will initially be small compared with the population size. Chapter 2 considers a model for diseases in which some of the cases exhibit no symptoms and are therefore difficult to observe. Examples of such diseases include influenza, mumps and polio. This chapter investigates the problem of determining whether or not the epidemic has died out if a period containing no symptomatic individuals is observed. When modelling interventions, it is realistic to include a delay between observing the presence of infection and the implementation of control measures. Chapter 3 quantifies the effect that the length of such a delay has on an epidemic amongst a population divided into households. As well as a constant delay, an exponentially distributed delay is also considered. Chapter 4 develops a model for the spread of an emerging strain of influenza in humans. By considering the probability that an outbreak will be contained within a region in which an intervention strategy is active, it becomes possible to quantify and therefore compare the effectiveness of intervention strategies.