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.

Therapeutic footwear is provided to patients with the primary aims of reducing foot pain and improving foot health. Therefore, it is of concern that patients choose not to wear it. This choice has been attributed to its poor appearance. However, there may be other reasons for this choice and the reasons may be more complex than previously acknowledged. Therefore, the aim of this study was to investigate the users’ experiences of this footwear. In the context of this study the ‘users’ are women with rheumatoid arthritis. This study was based on an interpretive phenomenological approach (IPA) that employed conversational style interviews to gather data. Ten women with RA and experience of wearing the footwear were recruited and following ethical approval the interviews were carried out, transcribed, organised and analysed. Five organising themes emerged as findings. These were the participants: • feelings about themselves, • feelings about the footwear, • unmet needs and expectations, • behaviour with the footwear and • feelings about the consultation with the practitioner. The final, global theme was that the patient/practitioner consultation has a powerful influence on the women’s feelings about themselves, the footwear, their expectations of it and their behaviour with it. This study has provided insight into their experiences of this footwear in that, unlike any other intervention, it replaces something that is normally worn and is part of an individual’s perception of self and their perception of how others see them. The footwear impacts more on women’s emotions than previously acknowledged and in addition, it has been found that the consultation influences their emotions and behaviour with the footwear. As well as improvements in footwear design and the service that delivers it, the training of the practitioners in a more patient focussed consultation style could improve the women’s experience and engagement in the footwear as a health intervention, as well as something that is ‘worn’.

Sol-gel derived bioactive glasses are promising candidates for bone regeneration, where bone is a natural nanocomposite of collagen (organic polymer) and hydroxyapatite (inorganic mineral) with a complex hierarchical structure and excellent mechanical properties. Solid-state NMR is a sensitive probe and offers atomic-level information on the structure of sol-gel derived bioactive glasses. In this thesis, a multinuclear solid state NMR approach, as part of an extensive study, has been applied to a key range of sol-gel derived materials related to novel nanocomposites to act as tissue scaffolds. The nanostructure evolution of sol-gel derived bioactive glasses 70S30C (70 mol% SiO2 and 30 mol% CaO) was characterised by 29Si, 1H and 13C CP MAS NMR. Calcium was found to be incorporated into the silica network during the stabilisation stage and to increases its disorder. The inhomogeneity found within 70S30C bioactive glass monoliths showed that the calcium concentration was higher in the outer region of the monolith caused by the way calcium only enters into the structure after breakbown of the nitrate. Trimethylsilylation reaction mechanisms used to tailor the nanoporosity of sol-gel derived 70S30C bioactive glass was also studied. The 29Si NMR results showed that the modification processes affected the atomic scale structure of the glass, such as Qn structure and network connectivity. 1H and 13C NMR was used to follow the loss of hydroxyls and organic groups directly. The study was extended to 58S (60 mol% SiO2, 36 mol% CaO, 4 mol% P2O5) systems and compared for two synthesis routes: inorganic and alkoxide. Via the inorganic route high temperatures were needed for calcium incorporation, while via alkoxide route calcium was found to be incorporated at low temperatures. Reactive surface Ca ions were involved in the formation of different types of carbonates for the two routes. The addition of P2O5 to the silica-calcium oxide system results in a scavenging of calcium ions by phosphate groups to give orthophosphate and pyrophosphate units. Solid-state NMR of new organic-inorganic hybrid scaffolds, class II, in the silicagelatin and silica-calcium oxide-poly(γ-glutamic acid) (γ-PGA) systems indicates that 3- glycidoxypropyltrimethoxysilane (GPTMS) provides a covalent link between the organic and inorganic networks and increased the inorganic condensation. 1H-1H intra- and intermolecular proximities have been identified using 1H DQ (double-quantum) CRAMPS (combined rotation and multiple pulse spectroscopy) techniques. 13C NMR results indicate that an efficient promotion of epoxide ring opening of GPTMS was reached by either gelatin or γ-PGA. 43Ca NMR identified different calcium environments in the hybrid systems. The last part of this thesis is focused on the comparison studies in the mechanism of apatite growth on both melt-derived (Bioglass®) and sol-gel derived (TheraGlass®) bioactive glass surfaces. By using a combination of 1H, 13C, 31P, 29Si and 23Na, using one and two dimensional NMR spectroscopy, the inhibitive effects of serum proteins in the mechanism of the apatite growth was revealed. The solid-state NMR experimental data support the hydroxycarbonate apatite formation mechanism proposed by Hench. Apatite formation takes place from the largely amorphous phosphate ions initially deposited on the glass surface. Serum proteins adsorbed on the glass surface have been found to significantly inhibit the apatite formation. Multiple sodium sites have been identified in Bioglass® composition with the formation of a more ordered local structure on increasing immersion time.

This thesis discusses issues arising in the analysis of repeated measurement studies with missing data. The first part of the thesis is motivated by a study where continuous and bounded longitudinal data form the outcome of interest. The aim of this study is to investigate the change over time in the outcome variable and factors that influence this change. The analysis is complicated because some patients withdraw from the study, leading to an incomplete data set. We propose a non-linear mixed model that specifies the rate of change and the bounds of the outcome as a function of covariates. This mixed model has advantages over transforming the data and is easy to interpret. We discuss different models for the covariance structure of bounded continuous longitudinal data. To explore the impact of missingness, we perform several sensitivity analyses. Further, we propose a model for informative missingness, taking into account the number and nature of reminders made to contact initial non-responders, and evaluate the impact of missingness on estimates of change. We contrast this model with the traditional selection model, where the missingness process is modelled. Our investigations suggest that using the richer information of the reminder process enables a more accurate choice of covariates which induce missingness, than modelling the missingness process. Regarding the reminder process, we observe that phone calls are most effective. The second part of this thesis is motivated by dose-finding studies, where the number of events per subject within a specified study period form the primary outcome. These studies aim to identify a target dose for which the new drug can be shown to be as effective as a competitor medication. Given a pain-related outcome, we expect many patients to drop out before the end of the study. The impact of missingness on the analysis and models for the missingness process must be carefully considered. The recurrent events are modelled as over-dispersed Poisson process data, with dose as regressor. Additional covariates may be included. Constant and time-varying rate functions are examined. Based on a range of such models, the impact of missingness on the precision of the target dose estimation is evaluated by simulations. Five different analysis methods are assessed: a complete case analysis; two analyses using different single imputation techniques; a direct likelihood analysis; and an analysis using pattern-mixture models. The target dose estimation is robust if the same missingness process holds for the target dose group and the active control group. This robustness is lost as soon as the missingness mechanisms for the active control and the target dose differ. Of the methods explored, the direct-likelihood approach performs best, even when a missing not at random mechanism holds.

The findings of this study provide an original contribution to knowledge in ankylosing spondylitis (AS) and have important implications for eiThancing clinical practice. The results demonstrate the existence and significance of associations between disease and psychological status in AS, and also demonstrate the value of using longitudinal, repeated measures approach to study this long-term condition. This study is also the first to demonstrate the value of using a mixed methods approach to investigate this issue in AS. Although existing literature on prospective longitudinal cohort studies in AS is very limited (other than for studies which involve clinical trials of medications and other interventions), this project demonstrates the feasibility of sustaining such a study over an 18-month period and of recruiting large numbers of participants to both the quantitative and qualitative phases. The results are based upon a hospital-ascertained cohort of 89 adults. Both the quantitative and qualitative phases produced important new findings: 1. In this cohort, mean BASMI, BASFI and BASDAI scores remained consistent throughout the 18-month period. People with BASDAI scores higher than 4 at the beginning of the study continued to score higher than 4 throughout. 2. BASMI, BASFI and BASDAI scores correlated significantly with anxiety, depression and internality scores, but not with levels of belief in chance or powerful others, throughout the study. This demonstrates that AS disease status is closely linked to some, but not all, psychological measures. 3. There was no effect of co-existent psoriasis or iritis on either disease or psychological status, but BASMI and BASFI (but not BASDAI) scores were significantly related to age. 4. Factors which appear to influence the associations between disease and psychological status are highly complex, often differing between individuals, and usually determined by other co-morbidities and life circumstances besides AS. These results suggest that the major implication for clinical practice would be the development of a more comprehensive and integrated assessment framework for AS set within the context of a biopsychosocial model. Envisaged would be a major programme of work to critically assess and validate potential components of such a framework with the aim of determining efficacy, feasibility and acceptability of such an approach.

This thesis reports six studies adopting a self-determination theory (SDT; Deci & Ryan, 1985) approach to understanding motivation and behaviour in health and social contexts. The research focuses on the internalisation and integration of goals and motives extrinsic to the individual and the effects of internalisation on psychological and behavioural outcomes. Two studies also explore the role of social agents in facilitating internalisation through provision of autonomy support. The research addresses gaps in the SDT literature and contributes to the advancement of theory and practice. A meta-analysis of effects of autonomy support on health-related psychological and behavioural outcomes (Chapter 2), based on the methods of Hunter and Schmidt (1994), indicated the significance and consistency of adaptive effects of autonomy support across the literature. A path analysis was also used to test a modified representation of Williams et al.’s (2006) SDT process model of health-related behaviour. Results supported the motivational sequence postulated within the model, as the effect of autonomy support on behaviour was mediated by need satisfaction and autonomous motivation. The studies reported in Chapters 3 and 4 make a novel contribution to the SDT health literature by employing measures of chronically-accessible physical activity outcomes and motives to represent spontaneous motivational influences on behaviour. The results presented in Chapter 3 indicated that chronically-accessible appearance-related outcomes are associated with controlling forms of motivation, while the findings reported in Chapter 4 showed that planning-based strategies to maintain physical activity under situations of success and failure in goal striving are differentially effective for chronically autonomous and controlled individuals. These studies also offer guidance for health practitioners in promoting physical activity, by highlighting the potentially maladaptive effects of appearance-related goals and the importance of tailoring planning-based interventions to individuals’ chronically-accessible motives. The study reported in Chapter 5 substantiated a core theoretical assumption of SDT by providing empirical support for people’s inclination to distinguish between intrinsic and extrinsic goals. Adopting methods from the literature on memory and attitudes, cluster analysis was performed on participants’ self-generated and recalled physical activity goal data to determine the presence of clustering by goal type. Although findings supported individuals’ ability to distinguish intrinsic and extrinsic goals at some level of representation, participants were not able to reliably code their goals at an explicit level. It was therefore concluded that differentiation between goal types may not occur consciously. The scale-development study in Chapter 6 also supported a key tenet of SDT in establishing construct, nomological, and predictive validity of a scale measuring integrated regulation for physical activity. The factorial validity of the scale, developed through an extensive literature search, expert ratings, and confirmatory factor analyses, was supported in both a high and a lower-active sample. Consistent with predictions, latent means analysis indicated the high active sample reported significantly greater integrated regulation. The scale provides a valid and reliable tool that may be used to evaluate the process of integration following autonomy-supportive interventions in health-related contexts. Finally, Chapter 7 details the development of a brief autonomy-supportive intervention and observational checklist system for ensuring fidelity to protocol that can be modified for use in a number of contexts requiring behaviour change. The intervention was implemented in a higher education setting over the duration of a single course module and significantly increased two autonomy-supportive teaching behaviours in postgraduate tutors. However, the intervention did not significantly increase the perceived autonomy support, self-determination, or coursework grades of the experimental tutors’ students relative to the control condition, although there was a trend towards a trend towards an interaction between time and experimental condition for level of self-determination towards studying. While students in the experimental group reported an increase in self-determination over time, students within the control condition reported a decrease in self-determination between the first and second, and first and third waves of data collection. The thesis concludes with a general discussion of findings and directions for future research and practice.

The work within the thesis aimed to integrate concepts from three psychological frameworks, including self-determination theory (SDT), the theory of planned behaviour (TPB), and the hierarchical model of motivation (HMM), into a model to understand the processes that underpin motivation and intention toward health and safety behaviours. The first tenet of the model (derived from SDT and HMM), namely the trans-contextual effect of motivation, hypothesised that self-determined motivation for a given activity related to self-determined motivation for undertaking health-promoting behaviour associated with the activity. The second tenet of the model (derived from the strength, limitation, and theoretical assumptions of SDT and the TPB) speculates that the effects of self-determined motivation for health and safety behaviour on intention and behaviour were mediated by social cognitive variables. A total of eight studies were employed to test the two tenets of the integrated model across various health contexts (i.e., sport injury rehabilitation and prevention (Study 1 to 5)), occupational injury rehabilitation and prevention (Study 6 and 7), and myopia prevention (Study 8), and these studies are presented in five related research chapters (Chapters 2 to 6) in this thesis. The results provided preliminary evidence in support of both tenets of the integrated model, in which motivation from a general life domain is transferred to motivation, and antecedent social cognitive variables, for behaviour in a health and safety domain. The final chapter (Chapter 7) of the thesis summarises the findings of the eight studies and offers explanations and interpretations of the overall pattern of results. Conclusions were then drawn with respect to the theoretical and practical implications of the findings. Consideration was also given to the methodological limitations of the thesis and the scope for further studies to improve the predictive power, utility, measurement reliability, and evidence base for the model.

This study reports on the analysis of the Mental Health Discourse Corpus. This dataset is comprised of four sub-corpora that contain patients' online discussions of anorexia nervosa, patients' online discussions of depression, general practitioners' discussions of anorexia, and general practitioners' discussions of depression, respectively. The methodology integrates quantitative corpus linguistic approaches with qualitative analysis drawing on Hallidayan functional grammar, discourse analysis and discursive psychology. By interrogating corpora of health communication across communicative modes and participants, the study offers novel insights into the verbal presentation of anorexia and depression by patients and professionals, and examines their respective uptake of medical explanations of mental illness. Common patterns in the online patient interactions are linguistic choices which realise the externalisation and personification of anorexia and depression, the discursive construction of individual helplessness, and the representation of psychological distress in terms of medical pathology. The uptake and proliferation of biomedical explanatory models of anorexia and depression serves to reduce illness stigma for individuals and, notably, is also used to perform local interactional tasks. In the practitioners' talk, participants draw on medical and social explanations of depression and anorexia. Doctors construct depression as a categorical medical diagnosis while also expressing doubt towards its medical treatment and advocating non-medical interventions. When discussing anorexia, clinicians emphasise the bureaucratic role which body mass index scores occupy in managing anorexia and repeatedly highlight the difficulty of overcoming patients' resistance. In both cases, participants highlight the bureaucratic and communicative challenges of working with anorexic and depressed patients and construct a range of unfavourable moral identities for the chronically ill. The practical implications of the research for users of online support groups and general practitioners working with depressed and anorexic patients are identified. In particular, I emphasise the centrality of communication to primary mental health care and the utility of studying online support groups to illuminate the experiences and beliefs of patients. A critical evaluation of the study's methodology is offered, along with recommendations for future research.

Diphenylalanine (FF) peptide is the core-recognition motif of β-amyloid polypeptide, a peptide associated with diseases such as Alzheimer’s and which is known to be capable of self-assembly. FF has attracted interest in nanotechnology due to the physical and chemical stability and mechanical rigidity of the self-assembled nanotube form of the peptide. A number of promising applications of FF nanotubes have previously been explored. To extend this work to biomedical and pharmaceutical areas, an improved understanding of the physicochemical properties of FF tubes, together with the influence of assembly conditions, cytotoxicity properties and potential in drug delivery field are presented in this thesis. The studies presented in Chapter 2 address the self-assembly of FF peptide prepared by two known methods of preparation, one aqueous based, the other utilizing an organic solvent. A range of complementary characterization methods is applied including atomic force microscopy, scanning electron microscopy, focused ion beam-scanning electron microscopy, X-ray powder diffraction, and Raman Spectroscopy. The investigations reveal differences in morphology of the tubes formed by the different preparation methods. The aqueous based method produces tubes that are long, straight and unbranched and are consistent with previous work. The alternative organic solvent method produced tubes that are shorter and narrower. In addition, these tubes displayed flexibility and nucleation points. Following on from these findings, a proposed mechanism of tube growth is discussed. Chapter 3 further extends the investigation to the biological field. Possible cytotoxicity issues are studied using a MTT assay on a HeLa cell line. Moreover, total internal reflection microscopy was applied to investigate HeLa cell behaviour in the presence of FF nanotubes. The results from these studies reveal that the nanotubes and FF peptide do not cause any mitochondrial related damage to HeLa cells. Furthermore, short tubes were observed to be taken up by cells through a suggested macropinocytosis pathway. Finally, in Chapter 4 the focus turns to the investigation of the potential of FF tubes as drug carriers in drug delivery. Here, successful synthesis of drug-loaded FF tubes is presented with two model drugs. The physical characterization of the complex formed under different conditions using scanning electron microscopy reveals FF nanotube self-assembly is a drug concentration and solvent type dependent process. Finally, in vitro drug release from FF nanotubes is performed and compared to that of the drug alone. Extended drug release is observed for both drug candidates and release mechanisms are proposed. The results presented throughout this thesis demonstrate the versatility of self-assembling FF peptides for the formation of tubular nanostructures with different morphologies and physical properties under different conditions. The assembled nanostructures appear non-toxic to cells and offer promise in drug delivery as novel drug carriers.

This thesis examines the healing strategies utilised by the inhabitants of Egypt during the Roman period (from the late first century BC to the fourth century AD) in order to investigate how Egyptian, Greek and Roman customs and traditions interacted within the province. It explores the symbiotic relationship between 'professional' and 'amateur' medical practice within Egypt, and examines the ways in which three particularly well-attested health problems - eye complaints, febrile conditions and the injuries inflicted by wild animals - were approached, evaluated and treated. By considering a range of literary, papyrological, archaeological, and anthropological sources, this thesis argues that healing strategies were developed in response to a variety of historical, cultural and social factors, and were intimately connected to the region's climate, geography and natural resources. This thesis, then, presents a fresh and nuanced approach to understanding healing strategies in Roman provincial culture, identifies diagnostic features of healing in material culture and offers an integrated reading of ancient medical literary and documentary papyri, and archaeological evidence. By encompassing the full spectrum of healing strategies available to the inhabitants of the province, and by incorporating elements of medical, surgical, magical and religious healing, it offers a comprehensive and wide-ranging perspective on healing in Roman Egypt, and investigates new approaches to the study of medicine in the Roman world.