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The increasing use of electronic, rather than paper-based, healthcare records provides enormous potential for health research. However, research-enabling such electronic health (e-health) records presents considerable challenges across several inter-connected domains such as database design and construction, creation of verifiable research pipelines, development, and application of appropriate statistical methods through to solutions for governance and privacy issues. In this thesis, I describe the development of a platform and demonstrate its application in risk prediction, pharmacoepidemiology and disease prevalence. The work in this thesis describes i) the construction of a research platform based on e-health records from the total population of Scotland with diabetes ii) the use of this platform to address several questions about the epidemiology and pharmacoepidemiology of diabetes complications relevant to the care of people with diabetes. The thesis consists of two major themes i) technical development of the platform that I designed as a software developer to enable the research to be achieved and ii) the application of appropriate study design and statistical methods as an emerging epidemiologist to answer specific research questions. Chapter 1 contains an overview of some of the challenges and approaches taken in the construction and use of research data platforms from e-health records. The chapter focuses on the informatics theme of the thesis. The introductory background to the specific research questions is given within the question-specific chapters. Chapter 2 describes the research platform that I designed and implemented. It summarises the types of data available in the platform and describes the cohort of those with diabetes in Scotland. These data and participants are then selected in the subsequent specific research studies. As such, it forms the equivalent of an overarching methods chapter for the remainder of the thesis. The manuscript has been submitted for publication and at the time of thesis submission was under review. In Chapter 3, I describe work I conducted and published using the research platform to provide a contemporary snapshot of prevalence of cardiovascular disease (CVD) and cardiovascular risk factors in all people with type 2 diabetes in Scotland. Cardiovascular disease is the leading cause of death and loss of life expectancy in both type 2 and type 1 diabetes, but the past decades have seen advances in the understanding of disease pathogenesis and its prevention. However, I found that prevalence remains high (about one-third of those with type 2 diabetes had already been diagnosed with CVD) and that two-thirds had suboptimal control of at least two modifiable risk factors for CVD. This demonstrated the ongoing impact of CVD in diabetes and delineated areas of unmet need with respect to known risk factor control. In Chapter 4, I demonstrate the use of the research platform for real-world pharmacoepidemiology. Specifically, it describes a study I conducted and published to test the effect of a new diabetes drug (dapagliflozin) on cardiovascular risk factors in people with type 2 diabetes. At the time of the study, it was unknown whether this drug would achieve the same effects in the real-world as it had in the much more idealised setting of short duration clinical trials. The analysis found that reductions in HbA1c, SBP, and BMI were equivalent to that of the clinical trials, and importantly that these effects were sustained over the median 210 day follow-up. Chapter 5 describes the quantification of current CVD incidence rates in people with type 1 diabetes in Scotland and the use of the research platform to construct a CVD risk prediction model for people with type 1 diabetes. I then used the Swedish national diabetes register to validate the generalisability of the model. There is considerable debate among clinicians about the appropriate age and circumstances under which cardiovascular risk modifying therapies (in particular, statins) should be prescribed in type 1 diabetes. Clinical guidelines assume a very high absolute rate of CVD from an early age and advocate basing treatment-initiation decisions either on the expected absolute rate over the ensuing decade or in some cases lifetime risk. Yet contemporaneous data on the actual current experienced risks are lacking. I found the current absolute rates to be much lower than the guidelines implicitly assume. I showed that under current guidelines, >90% of those aged 20-40 years and 100% of those >=40 years with type 1 diabetes were eligible for statins, but it was not until age 65 upwards that 100% had a modelled risk of CVD >=10% in 10 years, the threshold for statin use in the general population. The CVD prediction model I constructed was well calibrated and achieved high predictive performance in both Scotland and Sweden. The results should prove useful to facilitate individualised discussions regarding appropriate prescribing and the rationale for prescribing. In chapter 6, I describe my use of the research platform to rapidly address a sudden major challenge in diabetes, namely that of the SARS-CoV-2 pandemic. At the outset of the pandemic in 2020, a high preponderance of diabetes among those being admitted to hospital with COVID-19 was being reported. Yet most studies lacked a population denominator, so it was unclear just how large the risks were associated with diabetes, and if the clinical risks (of hospitalisation, admission to a critical care facility and death) were predictable among those with diabetes. It was also unclear whether all those with these risks should be in shielding. I found that by the end of the first wave of the pandemic the risk of severe COVID-19 was elevated 2.4 fold in type 1 diabetes and 1.4 fold in type 2 diabetes (much less than what was generally thought). The prediction for the cross-validated predictive model of severe COVID-19, retained 11 factors in addition to age, sex, diabetes type and duration and had good predictive performance (C-statistic of 0.85). The study results were reported to government and diabetes stakeholder groups early in the pandemic and were used to inform shielding policy. Chapter 7 presents an overall discussion of the work of the thesis, the lessons learned and future work focusing on the research platform development theme. The key findings and advantages of the work I have described in generating the data platform are: the importance of separating the analysis from the data; the ability to accommodate various data types from different data sources (flexible data input); longitudinal database formatting; the importance of an accurate metadata dictionary; a verifiable research pipeline; the compliance with governance, and the ability to generate synthetic datasets. The work in this thesis provides evidence of the feasibility and usefulness of harnessing e-health records for important and timely research that impacts on people with diabetes. It provides insights and exemplars of use that should be helpful for others in the field trying to develop such platforms for diabetes or other disease areas. Future work includes the development of a pharmacoepidemiology pipeline, allowing rapid analysis of safety and effectiveness outcomes, given a wide variety of exposures, and the ability to incorporate genetic and 'omics data.

Despite continual rising demand for atrial fibrillation ablation, numbers of cases performed have plateaued. One reason for this is a shortage of appropriately skilled sedationists. Administration of sedation by nurses using a protocol is a potential solution, but virtually no research exists on the impact of this on the quality of patient care. This project aimed to evaluate the use of such a protocol in a single NHS Trust in terms of safety and patient experience. By doing so, it was intended that it should ascertain the feasibility of protocol-based sedation by nurses, and identify areas in the practice studied requiring alteration in order to optimise patient outcomes. A two-stage mixed methods project was undertaken. An initial survey phase provided statistical data that allowed comparison between the safety of protocolised nurse-led sedation and other sedation practices. Fuzzy set Qualitative Comparative Analysis (QCA) of the survey data allowed for exploration of patterns of complexity between components determining patient experience, a possibility identified within existing theories of pain such as the 'Gate Control Theory'. Subsequently pathways leading to positive experiences were modelled. These pathways were then tested using a series of case studies to ascertain the existence of causal links between the identified factors and positive outcomes as well as the extent to which protocol-adherence facilitated positive outcomes. This thesis presents findings from both stages. These include the conclusion that nurse-delivered sedation is at least as safe as other methods. It establishes more than one pathway to positive patient experiences may exist, but finds strongest evidence that effective management of patient anxiety leads to a positive outcome. However, it also concludes that creating this outcome depends on the clinical judgement of the individual nurse, and identifies alterations in the status of the protocol and its content to facilitate optimal outcomes.

Three dimensional porous structures of graphene and carbon nanomaterials have many exciting uses in energy storage, as catalyst supports and for water treatment to name a few; thanks to their high surface area, record conductivity, stability and potentially abundant feedstocks. However, recent publications have highlighted the need for a greater understanding of these materials' formation and characterisation methods if they are to be optimised for these applications. Many graphene production methods result in a polydisperse mixture of flake sizes, thickness and chemical environment and understanding this complex distribution is important for many applications. Raman spectroscopy is a versatile method of graphene analysis but single point spectra cannot resolve this distribution and, in many cases, may misrepresent a material. By recording multiple spectra a statistical dataset is produced but the size required remains an important consideration. Herein a protocol was developed, utilising the convergence of data sets and a Monte Carlo based statistical method, to investigate the size of data set required for accurate characterisation. This was successfully applied to a range of carbon nanomaterials revealing different materials require bespoke analyses for complete characterisation, and even routine analysis can require hundreds of points. This characterisation was then applied to graphitic carbon produced from metal catalysed graphitization; whilst many studies have probed the effect of different process conditions, carbon sources and metals, here we investigate the role of different salts of the same metal, previously considered irrelevant to graphitization. By analysing the distribution of material produced from three different cobalt salts: $Co(OAc)_2$, $Co(NO_3)_2$ and $CoCl_2$; it was found the thermal stability of the metal source used is key to controlling the size of metal particle formed and thereby the pore structure and carbon produced. Such control can potentially be used to tailor the properties of carbon foams produced from low cost feedstocks.

Background: Abdominal solid organ transplantation has evolved from an experimental procedure to a well-established therapy within a few decades. This success is largely due to the introduction of calcineurin inhibitor immunosuppression. Tacrolimus is the most widely used calcineurin inhibitor but has a narrow therapeutic range which requires close drug monitoring to prevent both toxicity and inadequate immunosuppression. Previous studies in renal transplantation have shown that genetic polymorphisms, CYP3A5, CYP3A4*22 and ABCB1 can influence the bioavailability and pharmacokinetics of tacrolimus. These polymorphisms are closely linked to ethnicity and have never been studied in a Scottish population before. Additionally, increasing evidence suggests that high variability of tacrolimus is linked to increased graft loss in kidney transplant patients. Methods: 5889 subjects were genotyped for the genetic polymorphisms CYP3A5 A > G allele transition, CYP3A4*22 C > T and ABCB1 C > T transition. This included 4899 healthy individuals from Generation Scotland bio-resource and 990 patients who underwent renal, liver, or simultaneous pancreas kidney transplants or were organ donors. Tacrolimus dose, trough level and renal function were measured at 11 time points from date of transplant up to and including 12 months post-transplant. Clinical data including episodes of acute rejection, graft and patient survival were compared between the different genotypes. Separate analyses were undertaken for kidney, SPK transplants, as well as liver transplants, the latter looking at recipient and liver donor genotype. A separate cohort of 103 renal transplant patients converted from twice-daily to once-daily tacrolimus had their tacrolimus variability calculated and compared with graft survival. Results: The distribution of the 3 different genotypes of CYP3A5, CYP3A4*22 and ABCB1 were comparable with other Caucasian populations studied previously. In renal transplant recipient expression of the A allele (GA/AA) led to significantly increased dose requirements of tacrolimus and initially lower tacrolimus trough levels. The different genotypes of ABCB1 had no effect. Expression of a CYP3A4*22 T allele trended towards a lower tacrolimus dose requirement but this was not significant. There was no difference in renal function, graft survival or patient survival with any of the polymorphisms. SPK patients had comparable results. In the liver transplant patients, the donor genotype had a greater influence than the recipient one. The donors with CYP3A5 A allele expression had significantly higher tacrolimus dose requirements and lower initial tacrolimus levels. This was apparent to a lesser extent with the recipient expression of CYP3A5 and did not reach statistical significance at all time points. There was no significant difference in tacrolimus dose requirements or level with either donor or recipient expression of ABCB1 or CYP3A4*22. There was a significantly higher incidence of acute rejection in donor CYP3A5 A allele expressers of liver transplant patients in univariate and multivariate analysis. There was no significant different in acute rejection with ABCB1 or CYP3A4*22 genotype. No differences in graft or patient survival with either donor or recipient genotype of any of the 3 polymorphisms were noted. Conversion from twice-daily to once-daily tacrolimus in the first 12 months post-transplant reduced tacrolimus variability. Patients with high tacrolimus variability pre and post conversion had significantly greater graft loss than patients with low tacrolimus variability. Conclusion: CYP3A5 expression results in increased tacrolimus requirements to achieve adequate immunosuppression in renal transplant and SPK patients. Donor rather than recipient CYP3A5 expression is relevant for liver transplantation and dose requirements. There may be an association with donor CYP3A5 expression in liver transplant patients and acute rejection which needs further evaluation. ABCB1 and CYP3A4*22 do not appear to have a significant impact in any of the organ transplants. High tacrolimus variability is associated increased graft loss in renal transplant patients.

Over the past half century, theorists have grappled with the issue that spectators engage with, and are emotionally affected by, fiction. In particular, film fiction has aroused interest because of the strength of emotional response. Traditional thinking about film accepted that illusion was a component of a spectator’s experience of film. However, contemporary theory has veered significantly from this and assumed that the spectator is always aware of the fictional nature of the content. In this thesis I argue that certain horror movies do, in fact, lead to an experience that is best characterized and understood in terms of illusion. Analysing key theories that attempt to explain an audience’s emotional responses to fiction, I aim to demonstrate that popular non-illusionistic theories fail to acknowledge both sides of the filmatic relationship (the spectator and the film) and have mistakenly attempted to provide an explanation for all emotional responses across media. A more refined approach is needed, both to emotion and the medium through which it is evoked. Thus, I incorporate an empirical analytical method in my philosophical project, analysing a number of paradigm horror movies and drivers of film spectatorship, to demonstrate how conditions for illusion are present. I also place emphasis on the phenomenological account of the spectator. My thesis offers an account of a type of horror movie experience that considers both the causal and conceptual issues of emotionally responding to film fiction. This explanation also offers a solution to the paradox of fiction but one that is not required to accord with those that attempt to explain other emotions evoked by works of art.

Neural crest induction and migration is the culmination of an intricate network of signalling from both the ectoderm and underlying mesoderm. Due to the transient nature of the neural crest, little is known about the specific interactions of growth factors and morphogens required for correct patterning. Neural crest stem cells were differentiated from embryonic stem cells in serum-free feeder-free culture conditions. Cells were further differentiated into functional peripheral neurons, expressing the synaptic protein neurexin3, able to spontaneously generate action potentials and showing responses to the neuroactive compounds GABA and NMDA. Microarray analyses and subsequent RT-qPCR experiments revealed that gene expression of the key pluripotency associated factor Oct-4 was initially downregulated upon differentiation before expression levels increased as cells developed into a neural crest phenotype. Further experiments indicated an intrinsic role for bone morphogenetic protein-4 (BMP-4) in mediating this resurgence of expression. In addition to BMP-4 influenced expression of Nanog, members of the developmental pluripotency associated family of genes and important adhesion molecules with roles in the epithelial to mesenchymal transition of the neural crest. Global gene expression profiling of differentiating functional neurons offers new insights into BMP-4 mediated patterning of the neural crest and peripheral nervous system during development. This study implicates BMP-4 as a key factor in neural crest differentiation, with a role in diverse cellular processes including proliferation, fate determination and cell migration. The role of BMP-4 in mediating expression of pluripotency and adhesion factors highlights a potential role in oncogenesis; neural crest cells share many phenotypic traits with cancer cells. Finally, the generation of functional peripheral neurons in feeder free culture conditions offers a reliable method for the recapitulation of these tissues and the possibility of use in future tissue replacement therapy.

This thesis studies the American Equal Rights Association (AERA), 1866 to 1870, and argues for its historical distinctiveness and significance. The AERA was the only organisation in nineteenth-century America that explicitly campaigned for the rights of men and women on the same platform. Formed in the immediate aftermath of the American Civil War, the AERA joined the discussion of how to reconstruct the war-torn nation, demanding political rights to be extended to all American citizens based on their common humanity. As the first academic study to focus purely on the AERA, this thesis presents a series of new findings and interpretations about the association. It studies the creation, exploits, and demise of the AERA, highlighting and analysing key aspects of the association’s character, from its membership and ideas, to its campaigning and organisational dynamics. It also broadens the source base beyond the two figures of Elizabeth Cady Stanton and Susan B. Anthony, who have long dominated writings on the woman suffrage movement. Instead, the thesis examines the AERA membership as a whole. In so doing, it argues three main points: first, the association was more than just the vehicle for the woman suffrage movement at this time; second, the association worked well and was not constantly beset by divisions and disputes, and third, the final collapse of the association was due more to the actions of individuals than to wider historical or contextual forces. Besides arguing for the historical distinctiveness and significance of the AERA, this focus on the association itself provides a new angle on wide-ranging questions, concerning Reconstruction history, political relations between men and women and the role of men in movements for gender equality.

This thesis deals with the family of small molecules known as perylene diimides, their synthesis, properties, and use in organic electronics. In particular it is focussed on the use of perylene diimides as small molecular organic semiconductors in organic photovoltaics and organic field-effect transistors. Here is reported the synthesis, characterisation, properties and device testing of a range of new perylene diimide materials, designed to have properties amenable to use as acceptors in organic photovoltaics. Also reported is a method for the kinetic resolution of dicyano substituted perylene diimides, an important sub-group commonly used in organic field-effect transistor applications, to obtain regioisomerically pure samples of the majority regioisomer from an otherwise inseparable mixture. The effect of this purification on the physical and device properties is reported. A new kind of perylene diimide material was discovered during the course of this work. The identification of the new material, determined by a combination of spectroscopy and modern computational chemistry techniques is reported, as well as properties relevant to the use of the new material in organic electronics. Finally, the synthesis, characterisation and properties of a new dicyano perylene diimide is reported, in order to investigate the use of targeted thermal treatment on organic field-effect transistor device performance.

Solution Focused Brief Therapy (SFBT) has been applied in various settings in different countries for several years. Recent research suggests that a factor that appeals to the professional user is the creative application of the approach, exemplified in the wide and varied use in Educational Psychology (EP) practice. Despite this growth in the variety of applications there are limited examples of the use of SFBT with groups of parents in a context where a number of more structuralist approaches to parenting work are currently being offered by Local Authority and EP services. Applying a social constructionist approach to parenting work through a workshop model based on SFBT was therefore thought to be a useful development for practitioners who favour working within this paradigm. Drawing from the constructivist paradigm the aim of this study was to understand the experiences of parents and professionals of attending workshops that had been developed based on the principles of Solution Focused Brief Therapy (SFBT). The research takes the form of case study in the sense that the ‘Case’ that is being studied is the workshops themselves and the process of their delivery to a group of parents. Data was gathered from co-deliverers of the workshops as well as the parents themselves through a series of semi-structured interviews and focus groups. This was analysed using thematic analysis. The findings indicated that a number of elements of the workshops were important, including: questions as to why people had been asked to attend and how they became engaged in the approach on initially attending; the importance of feeling comfortable and socially at ease; some specifics regarding the nature of the SFBT approach; the changes in thoughts and behaviour that had taken place between the start of the process up to the three month follow-up period. Each parent reported degrees of positive change and the story regarding these changes is explored, along with reflections by the researcher. The extent to which SFBT contributed to engagement and outcomes is discussed along with the future possibilities for this way of working with parents.

The Cicipu language (Kainji, Benue-Congo) of northwest Nigeria has the kind of robust noun class system characteristic of Benue-Congo languages - GENDER agreement is found on a great many agreement targets inside and outside the noun phrase. For a number of these targets, gender agreement is in competition with a separate paradigm, that of PERSON agreement. The dissertation focuses on the distribution of this alternation with respect to subject prefixes, object enclitics, and pronouns, based on a corpus of 12,000 clauses of spoken language. The alternation proves to be complex to describe, involving a constellation of lexical, phonological, morphosyntactic, semantic and discourse-pragmatic factors. In particular, both animacy and topicality are CONDITIONS (Corbett 2006) on agreement. While inanimate or animal participants normally trigger gender agreement, if they are topics then they may trigger person agreement. Likewise while human nouns typically trigger person agreement, this is not always the case, and gender agreement is more likely if the referent is of incidental importance to the discourse. Furthermore it is argued that this alternation is sensitive to discourse topic (e.g. Dooley 2007) rather than sentence topic (e.g. Lambrecht 1994). Both gender and person subject prefixes are ambiguous agreement markers according to the typology of Bresnan and Mchombo (1987) and Siewierska (1999), since both can take part in grammatical or anaphoric agreement. Thus the Cicipu data supports Culy's (2000) contention that topicality is an independent dimension for the classification of agreement markers, rather than derivative of the grammatical vs. anaphoric agreement distinction, and leads us to re-evaluate the common assumption that dependent person markers (Siewierska 2004) cannot vary with respect to their discourse function. Since Cicipu is otherwise undescribed, a major part of the dissertation consists of a phonological and grammatical sketch.

The new control techniques of off-line model predictive control and level set methods have been applied to the challenges of engine management for diesel exhaust aftertreatment. Theoretical work has been supported by experiments carried out in a diesel engine test cell. A control relevant air-path model was developed using experimental work carried out on a diesel engine and dynamometer, with the aim of improving the engine control during the transients required by aftertreatment devices. This was considered as a two input and two output system, using an intake throttle and a valve associated with the exhaust gas recirculation system to control the in-cylinder quantities of fresh air and exhaust gas. Model predictive control techniques were used to design a hybrid controller, which was compared to a traditional proportional and integral controller and a 1-{00 controller in simulation. Level set methods were used to analyse supervisory hybrid control of a lean NOx trap model. In this system periodic mode changes are required to purge the NOx trapped on the filter and convert it to less harmful products. A novel diesel particulate filter model suitable for control was developed to represent the thermal wave behaviour observed in worst-case regenerations, where the soot in the filter burns to create local high temperature regions. A DPF was instrumented and fitted to the diesel engine and tested in the development of this model, particularly focusing upon these worst-case conditions. This new theoretical model was analysed using level set methods in a comparison with a simple control oriented DPF model. A supervisory hybrid control strategy to determine when to take emergency action to avoid thermal damage to the filter was designed using the simple DPF model. This strategy used safe conditions verified from the experimental work undertaken.