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This thesis examines the affordances of archival research in elucidating the compositional praxis of the composer Thea Musgrave (born 1928), informed primarily but not exclusively by the papers she sold in tranches from 2009 onwards to the British Library (GB-Lbl), where they were arranged and catalogued as part of the research for this thesis. These papers elucidate facets of Musgrave’s praxis that are not always apparent from her publications and other primary sources. The archive thus broadens the domain of primary-source evidence, yet it is still a mediated collection that is not in all respects representative. Such mediation, inasmuch as it is conditioned by the praxis under interrogation, elucidates implicit priorities. Indeed, as a composer who is still professionally active, the transfer of papers to archival collections itself forms part of her praxis. This researcher, whilst maintaining critical distance, has also availed himself of the particular opportunities afforded by a living subject, having conducted a pair of interviews with Musgrave. Through the evidence afforded by archival papers and other primary sources, this thesis situates Musgrave’s compositional praxis in relation to wider traditions, practices, and professions. Her purview as composer extends beyond devising and notating musical ideas, to encompass various artistic, technical, and ambassadorial activities furthering a tacit quest for canonical status for her oeuvre. As a published composer working to commission, her praxis is artisanal and collaborative to some extent, yet her compositional response is still demonstrably individual, and she retains a prerogative as composer resembling an auteur paradigm.

This thesis concerns the ideas of management accounting and control, as it examines poverty management, oral accounts and social control perspectives in a Bangladeshi Microfinance Institution (MFI). It traces how poverty management technologies are put in place and traditional oral accounts and social control mechanisms are expropriated for microfinance operation in the village. It ultimately seeks to understand how an alternative form of management accounting and control was made operable in a rural setting. The research involved intensive ethnographic fieldwork with in-depth interviews, direct observations, and documentation reviews. Drawing on the theoretical notions of the ‘society of control’ and ‘ethopolitics’, it illustrates how microfinance technologies are put in place to work especially in the emerging terrain of a control society; whether microfinance toolkits form a set of disciplinary and biopolitical mechanisms for the management of poverty; how local networks, social relations etc. are materialised in the making of a particular version of control society; how oral accounts are produced in such settings; how community ethos and values act as important aspects of ethopolitical social control systems; and how social controls are accommodated, reproduced and sustained for management control purposes in microfinance operation. It was the emergence of MFIs that integrated management accounting and control with household and village exchange relations, their social structures, and associated values and beliefs. This analysis makes several contributions to management accounting and control: first, by revealing poverty management technologies that MFIs design, modify and retain to monitor, report and evaluate the lives of poor people; second, to the discussion of accounting presence and absence; third, to the oral and verbal use of accounting; fourth, to the discussion of social control mechanisms; and finally, to the issues of microfinance in accounting. The thesis also has some theoretical contributions: first, it adds to the discussion of accounting in post-panopticon organisations; second, it shows the existence of alternative mechanisms of control while the organisation is in the becoming process; and finally, it employs ethopolitics as a governmental strategy which is unique in the accounting literature.

This thesis consists of five chapters. In the first chapter I provide the introduction to the three essays examined in this thesis. In the second chapter I examine the impact of securitization on U.S. bank holding companies’ (hereafter BHCs) credit risk, credit risk taking, profitability, and capital level between 2001 and 2013. I also study the effect of the credit enhancements and liquidity provision on BHCs’ performance between 2001 and 2013. Since securitization is an endogenous decision, I use the treatment-effects model to control for the selection bias and observe a positive relationship between securitization and credit risk. I also find that securitization decreases BHCs’ profitability, but that securitization increases BHCs’ capital levels. Although it is possible that relatively risk-averse BHCs may consciously increase their capital buffer by retaining earnings, for example, I do not exclude the possibility that BHCs engaged in regulatory capital arbitrage to increase their capital level. Nevertheless, I find that use of securitization for capital regulatory purposes is mitigated by the risk-retention mechanism, i.e. credit enhancements and liquidity provision—banks had to keep the required capital for their extended guarantees. However, as was uncovered during the financial crisis, these credit and liquidity risk-reducing tools were not sufficient to prevent the recent turmoil in the securitization markets. The third chapter analyzes information opacity and systemic risk for the U.S. BHCs in the context of the asset-backed commercial paper (hereafter ABCP) between 2001:Q2 and 2012:Q4. Banks which set up costly ABCP conduits might have benefited from the regulatory capital relief and from providing financing alternatives to their clients. However, they faced costs in terms of the increase in information opacity through the provision of ABCP guarantees to BHCs’ own and third-party sponsored ABCP conduits. Furthermore, I observe that higher information asymmetry about BHCs’ value is associated with higher volatility of returns and also with higher systemic risk. In the fourth chapter I examine the proposal to limit bank size, which is known as tackling the banks’ incentive to become “too big to fail”, and also how this regulation to curb bank size may affect banks’ operating costs. I examine the relationship between the size of BHCs and BHCs’ operating costs from 2001:Q2 to 2014:Q1 to evaluate the costs that the newly suggested regulations on bank size might bring. I find that rules to limit the size of banks could significantly reduce economies of scale. In particular, if large and cost-efficient banks become split into smaller parts, data processing, legal fees, audit and consulting expenses, in addition to expenses on premises and automated teller machines (hereafter ATMs) are likely to increase. I also pay particular interest to legal fees and litigation settlement; I find evidence that larger banks, but not necessarily systemically more risky banks, face litigation charges more frequently. I do not find evidence that larger banks face a lower probability of being fined. This suggests that another phenomenon known as “too big to jail” may not be true, if the assumption is that the misconduct detection is perfect. I do, however, observe that penalties had little effect on BHCs’ profitability, and that some of the largest banks continuously face litigation charges. In turn, this could possibly imply that benefits from wrongdoing outweighed the costs. The fifth chapter summarizes major findings and concludes.

Background: Public health researchers and practitioners have repeatedly called for policy to be informed by academic evidence. The rise of the evidence-based medicine movement has demonstrated the potential benefits of using evidence for clinical decision-making. Recently, politicians and policy documents have echoed these calls for increased use of evidence in policymaking by drawing upon the discourse of evidence-based policy. However, efforts to understand the relationship between evidence and public health policy are underdeveloped and often make limited use of knowledge from other fields, including political science and sociology. This thesis aims to explore the relationship between evidence and public health policy in the UK using two contemporary case studies: the English public health White Paper, ‘Healthy Lives, Healthy People’; and the development of minimum unit pricing of alcohol in Scotland. Methods: The first case study: ‘Healthy Lives, Healthy People’ case study investigates the extent that three prominent discourses that draw upon academic work are reflected by the policy statements contained within the White Paper. The three areas examined include evidence on ‘what works’, the Nuffield framework on public health ethics and insights from behavioural science (‘nudge’). These discourses were chosen as they are not only rhetorically prominent in the White Paper, but also because they reflect the range of direct use of specific research findings and more conceptual use of research-derived ideas. To examine the extent that evidence on ‘what works’ has been incorporated into ‘Healthy Lives, Healthy People’, the research evidence for each of 51 specific policy actions described in the White Paper was reviewed. A critical analysis of ‘nudge’ and the Nuffield framework was conducted by contrasting their application with the authors’ original articulation. The second case study explores the development of the high-profile public health policy of minimum unit pricing of alcohol by drawing upon three different sources of data. First, a review of policy documents was conducted. Second, a systematic document analysis of evidence submissions that were received by the Scottish Parliament’s Health and Sport Committee in response to its consultation on minimum unit pricing was performed. This analysis drew specifically on a framework for analysing political argumentation. Third, 36 semi-structured interviews were carried out with a broad range of policy stakeholders. Interviewees were purposively chosen to obtain diversity in supportiveness for minimum unit pricing, as well as by professional position (academic, advocate, civil servant, politician, industry representative). The evidence submissions and interview data were thematically coded and organised using NVivo 9. Results: By systematically assessing the evidence underpinning the English public health White Paper, the study empirically established that public health policy does not meet conventional public health standards for being evidence-based. Similarly, the prominence of ‘nudge’ and the Nuffield framework in the text of ‘Healthy Lives, Healthy People’ do not appear to be matched by the actions suggested. However, this first case study finds that while evidence does have an influence, it does not determine policy. This relationship appears complex, partial and contingent rather than direct and instrumental, therefore necessitating a more detailed and focused case study. The second case study begins by providing a detailed description of the process by which minimum unit pricing developed in Scotland. It then draws on the analysis of evidence submission documents combined with interview data to identify a crucial role of public health advocates, who reframed the alcohol policy debate to bring about policy change. Epidemiological concepts were important in helping to achieve this shift in policy framing. Having investigated more conceptual influences of evidence, econometric modelling carried out by a team at the University of Sheffield is focused on as an example of a specific piece of research evidence that was perceived by interviewees to be influential in the policy debate. The different types of influence that the modelling study had on the policy process are determined and reasons for its influence investigated. The study also finds that interviewees believed econometric modelling could be more widely used to inform future public health policymaking. Lastly, a ‘multiple lenses’ approach builds upon these findings and political science theory to produce a comprehensive explanation of the policy process and describe the roles of evidence on the minimum unit pricing policy process. Discussion: Analysis of the ‘Healthy Lives, Healthy People’ White Paper shows that despite the prominent rhetoric for evidence-based policy, this is not reflected by the reality of current public health policy in the UK. The investigation of the development of minimum unit pricing of alcohol in Scotland demonstrates that evidence influences the policy process in a number of ways but these influences are heavily context-dependent. The role of evidence in changing the framing of the policy debate has been identified as of particular importance for this case study. The devolution process and evolving nature of political institutions also raises particular opportunities, but also challenges, for public health professionals. The strengths of the thesis include its use of two case studies to investigate the relationship between evidence and public health policy, the analysis of multiple sources of data in relation to minimum unit pricing policy and the application of political science theories that are typically underused in public health research. Limitations include the caution required when making generalisations from these data, particularly since these case studies have been purposively chosen. Drawing upon the two case studies, a conceptual model for the relationship between evidence and public health policy is articulated. The model suggests that evidence is likely to be used in different ways depending on the extent that the political values underpinning an issue are contested, with the importance of evidence for rhetorical purposes being a legitimate and helpful means of highlighting the health aspects of public policy issues. Lessons for public health researchers and practitioners, as well as directions for future research and theoretical implications, are considered and discussed.

The main part of the work described in this thesis is concerned with the determination of the crystal and molecular structure of pteridine by X-ray crystallographic methods. The unit cell dimensions and space group of 'substance P', a dipteridyl derivative of unknown structure were also obtained. An additional paper deals with an investigation of the structure of the cellulose fibre sisal with the electron microscope. Pteridine crystallises in the orthorhombic non-centrosymmetrical space group Pna2 1 (C9 2v), molecules per unit cell. The unit cell dimensions are a = 24.70, b = 3.79, c = 6.32 A. The crystal and molecular structure has been determined with coordinate standard deviations of about 0.03 A from a study of Fourier and Fourier difference syntheses projecting on (010) and (001). The molecule is planar to within 0.06 A and the bond lengths vary between 1.28 and 1.41 A for carbon-nitrogen bonds and between 1.35 and 1.42 A for carbon-carbon bonds. The experimental bond length measurements are compared with molecular orbital calculations and are found to agree to within the limits of the experimental errors. The investigation was hampered by the fact that owing to the nature of the crystals only less than half of the possible reflections could be observed with CuKa radiation. Additional difficulties were caused by the non-centrosymmetrical nature of the one projection which gives good resolution and also by the difficulty of distinguishing between carbon and nitrogen atoms. The peak heights in the final electron density projection on (010) confirm the position of the nitrogen atoms, and the hydrogen atoms are also resolved.

The deuteration of optically active mandelic acid was investigated by shaking it in a sealed, evacuated tube under various conditions of temperature, and with different catalytic agents. The effect of acid, base, and platinum catalysts was examined, and in each case the degree of exchange occurring in the alpha position of the mandelic acid was correlated with the simultaneous change in its optical activity. The results indicated that with a basic catalyst present, the reaction occurred by a racemisation mechanism, an attacked molecule having an equal chance of retaining its configuration or undergoing an inversion. The platinum-catalysed exchange in acid solution was more complex, with both racemisation and retention mechanisms playing a part. With no catalyst present, racemisation of the acid occured, but without a corresponding exchange. In presence of platinum, the benzene ring, as well as the alpha hydrogen atom, was deuterated. These conclusions were confirmed by resolutions of the deuterated mandelic acid, when the observed deuterium contents of the resolved fractions were found to be in good agreement with the figures calculated assuming the mechanisms postulated for the first part of the experiment. The resolution also showed that alpha hydrogen exchange and nuclear deuteration were quite independent. Mechanisms for the various reactions have been suggested, and involve an Initial ionisation of the alpha hydrogen atom, either on the catalyst surface, or under the influence of a basic catalyst. The racemisation without exchange is considered to occur by a mechanism involving an initial fission of the bond between the alpha carbon atom and the carboxyl group.

The starting material for this investigation consisted of 22.5 kilograms of the dry powdered root of Gelsemium sempervirens, Aiton, and the object of the work was the isolation of the alkaloidal constituents of the root, followed by their chemical investigation. On account of the fact that sempervirine is unstable to heat, and is resinified to a large extent in boiling alcohol, it was decided, after some preliminary experiments, to carry out an extraction first of all with cold rectified spirit, followed by an extraction with boiling alcohol. It was decided also to use the method of separation (14) devised by Sayre for the isolation of gelsemine, sempervirine, and the amorphous alkaloids, and also to attempt the isolation of gelsemicine from the gelsemine mother liquors as described by Chou (15) , with certain small modifications in each case. This was done and the yields of gelsemine and sempervirine were found to be very much larger than those recorded by Sayre, particularly in the case of the latter. This was due, presumably, to the employment of a cold alcoholic extraction. The yield of gelsemine obtained was 0. 13% compared with 0.07% recorded by Sayre (14) and that of sempervirine (as nitrate) was 0.084% compared with 0.026% reported by Sayre. A small quantity of an amorphous alkaloid, not previously reported, was found in the gelsemine fraction, but could not be obtained crystalline. This alkaloid was found to be very slightly soluble in water and alcohol on long heating. The melting point of this amorphous alkaloid is 324d. An amorphous piorate was formed from water but could not be crystallised. On evaporating this alkaloid to dryness with hydrochloric acid a crystalline hydrochloride was formed, melting above 340, but owing to the extreme solubility of this hydrochloride and the small amount available, it was not found possible to prepare a sufficient quantity of the pure material for analysis determinations. Prom the fraction of the amorphous alkaloids called gelsemoidine by Sayre, there has been isolated a crystalline methiodide not previously reported. Analysis figures for this methiodide indicate a formula of either C20H24O3N2. CH3I or C20H22O3N2. CH3I. The melting point of this methiodide suggests its identity with apogelsemine methiodide C20H24O3N2. CH3I (melting points 296-297d. and 295d. respectively), but the determination of its specific rotation would seem to discount this view. The value Moore (11) has found for the specific rotation of apogelsemine methiodide is [x]D+12.4. An attempt was made to repeat, as far as possible, the conditions employed by Moore for apogelsemine methiodide, for the determination of the specific rotation of "gelsemoidine" methiodide. This has, however, been found impossible, the new methiodide being less soluble in water than apogelsemine methiodide has been recorded to be. A saturated solution was used for the determination and a value of [a]20D +3.9 was found. For comparison purposes the specific rotation of gelsemine methiodide was determined, and found to differ slightly from Moore's value. The value found was [a]10D+6.0, compared with that of [a]D +8.9 recorded by Moore(10). These results for gelsemine methiodide are in much closer agreement than those for "gelsemoidine" methiodide and apogelsemine methiodide, and it seems possible that the methiodide isolated from the gelsemoidine fraction is not, in fact, identical with apogelsemine methiodide. This possibility is, to a certain extent, enhanced by the fact that neither Sayre nor the present author were able to obtain "gelsemoidine" hydrochloride in the crystalline state, whereas apogelsemine hydrochloride is a crystalline substance. No attempt was made to prepare apogelsemine methiodide for comparison purposes as, for the isolation of pure apogelsemine, a relatively large expenditure of gelsemine would have been involved. The attempted isolation of gelsemicine was not successful, this fraction consisting of a dark brown tarry material which contained some gelsemine.

The following C1, C10- substituted chloro-nitrosocamphanes have been synthesised: The effect of irradiation with polychromatic red light was determined by both spectrophotometric and polarimetric measurements. The absorption spectra of compounds (b) - (e) showed bathochromic shifts after short exposure while that shown by (a) was hypsochromic. The reinvestigation of the spectra of the previously described chloro-nitrosocamphanes (f) and (g) (R = Me and CH2SO3 H+. Py respectively), also revealed changes in l max. after irradiation. Thus all chloro-nitrosocamphanes investigated showed, to varying degrees, changes in their spectra after irradiation. The Cotton effects and C2- configurations of (a), (b) and (g) were opposite those for the parent camphane (f). The irradiation of (a) and (f) resulted in the rapid inversion of their initially opposite curves of rotatory dispersion with a simultaneous displacement of their spectra in different directions. These observations are interpreted in terms of a 2:2' - mutarotation which gives the diastereoisomer with different molecular constants and hence a different spectrum. The polarimetric and absorption measurements for (b) and (g) however, are not easily reconciled with this hypothesis. Irradiation resulted in much greater increases in absorption on the long-wave side of l max. , while their Cotton effects did not change sign. Indeed for comparable changes in their spectra, the rotation of (b) changed by only 166 compared with the 1460 shown by (f). Various alternative causes of band-shift are discussed and shown by experiment to be untenable. The possibility of Wagner-Meerwein and Nametkin rearrangements induced by light is discussed and shown to provide a qualitative interpretation of the differences in the photo-processes of (b) and (g) on the one hand and (a) and (f) on the other. On this basis, the stereochemistry of the molecules determines the nature of the process. Experiments, in which it was hoped to differentiate between photomutarotation and intramolecular rearrangement in (b) and (g), are described. Although it was shown that, like (f) , the product of irradiation of (b) was isomeric with the starting material, the results of these experiments are inconclusive. The substituted chloro-nitrosocamphanes are shown to be theoretically capable of asymmetric photolysis but with greatly impaired efficiency.

The photochemical action of nitrosyl chloride on compounds of the type R1- C - R1 has proved to be of very limited application. Although isopropyl chloride gave beta-chloro-beta-nitroso propane, sec-butyl chloride gave not the desired beta-chloro-beta-nitroso butane but betagamma-di-chloro-beta-nitroso butane. Other compounds such as isopropyl bromide and betagamma-dichloro butane did not react. The possibility of using pinacolyl chloride has been discussed and has been ruled out owing to the inability of obtaining the substance readily and in its active form.

This thesis aims to highlight the dilemmas within education provision for disabled pupils. This is the product of competing frameworks, coming from different historical and philosophical contexts. The Warnock Report (1978) only managed a partial transition within education for disabled pupils from segregation to inclusion. This midway stage of integration continued the bureaucratic and professional dominance over access to additional support and continued to segregate the most affected pupils despite using humanitarian and equality rhetoric to defend its position. Throughout the 1980s and 1990s this tension led to wide variation in policy interpretation throughout the UK, yet the SEN policy framework went largely unchallenged until the Disability Discrimination Act (DDA, 1995) launched the Special Educational Needs and Disability Act, also known as Part 4 in 2001 (DDA, 2001). The DDA attempted to impose a rights-based model of equality on education. The survey data and qualitative in-depth interviews generated by this thesis show that the existing tension fuelled a resistance that has challenged a thorough engagement with the DDA. Further the surveys sent to schools and local authorities suggest that insufficient time was afforded the DDA Part 4 to impact on Scottish schools before new legislation was introduced and ratified in Scottish law (Additional Support for Learning Act, 2004). In-depth interviews exploring the system of complaint under the DDA Part 4 revealed a further tension between impairment effects and social expectations of discipline in schools related specifically to a diagnosis of Attention Deficit Hyperactivity Disorder, or allied conditions. In following the ethos of the social model, this thesis concludes that the DDA Part 4 failed to account for the differentiation of experience within the disabled community, and so offered little support for those most challenged by the pedagogical structures in schools. Based on the findings of this thesis, the DDA Part 4 has had little impact on Scottish schools, due in part to the tension within the competing SEN framework and timing of other policies. In addition inherent flaws within the terms of the DDA Part 4, including the omission of auxiliary aids and services from the remit of discrimination, contributed to its failure to impact on Scottish schools.

This thesis studies physical activity levels, pulmonary rehabilitation and their effects in participants with difficult-to-treat asthma associated with elevated body mass index (BMI). The three results chapters present the original research which I conducted during my period of study. All three chapters are presented as contracted papers, two of which have been peer-reviewed and published in scientific journals. This thesis has been approved for submission as an 'alternative format' thesis by the Higher Degrees Committee of the University of Glasgow. The focus of the thesis is exercise in participants with difficult-to-treat asthma associated with elevated body mass index. There are two research questions addressed by the thesis, do asthma severity or body mass index affect physical activity levels in asthma? The first results chapter concludes that they both do. Secondly, does pulmonary rehabilitation improve asthma control in this group of participants? The results of the work suggest that it may lead to some improvements in asthma control, but not to a clinically significant degree. "Physical activity levels in asthma: relationship with disease severity, body mass index and novel accelerometer-derived metrics" was published in the Journal of Asthma, online version published 2nd August 2022. This paper reports physical activity (PA) levels in participants with varying degrees of asthma severity and body mass index (BMI). It incorporates the use of two novel accelerometerbased metrics and how they correlate with asthma control. This paper provides an introduction into how difficult-to-treat asthma and elevated BMI affect physical activity and leads onto the main work in pulmonary rehabilitation. "A pragmatic randomised controlled trial of tailored pulmonary rehabilitation in participants with difficult-to-control asthma and elevated body mass index" was published in BMC Pulmonary Medicine, online version published 24th September 2022. This paper presents the initial outcomes at completion of an eight-week asthma-tailored pulmonary rehabilitation programme, comparing participants who completed PR with a control group who had usual care. The final results chapter, "Immediate and longer-term effects of an asthma tailored pulmonary rehabilitation programme in overweight and obese participants with difficult-to-treat asthma" has been submitted to Respiratory Medicine, to be considered for publication. This paper presents wider results of the above trial in a prospective observational format, as everyone who was randomised to usual care was invited to participate in PR after completion of the initial 8-week observation period. Here we consider the immediate and longerterm outcomes of a larger group of participants undergoing PR, and look at possible predictors of response.

This thesis is an alternative format submission comprising a set of publications and a comprehensive literature review, an introduction, and a conclusion. Continuous compliance with data protection legislation on many levels in the Industrial Internet of Things (IIoT) is a significant challenge. Automated continuous compliance should also consider adaptable security compliance management for multiple users. The IIoT should automate compliance with corporate rules, regulations, and regulatory frameworks for industrial applications. Thus, this thesis aims to improve continuous compliance by introducing an edge-server architecture which incorporates searchable encryption with multi-authority access to provide access to useful data for various stakeholders in the compliance domain. In this thesis, we propose an edge lightweight searchable attribute-based encryption system (ELSA). The ELSA system leverages cloud-edge architecture to improve search time beyond a previous state-ofthe-art encryption solution. The main contributions of the first paper are as follows. First, we npresent an untrusted cloud and trusted edge architecture that processes data efficiently and optimises decision-making in the IIoT context. Second, we enhanced the search performance over the current state-of-the-art (LSABE-MA) regarding order of magnitude. We achieved this enhancement by storing keywords only on the trusted edge server and introducing a query optimiser to achieve better-than-linear search performance. The query optimiser uses k-means clustering to improve the efficiency of range queries, removing the need for a linear search. As a result, we achieved higher performance without sacrificing result accuracy. In the second paper, we extended ELSA to illustrate the correlation between the number of keywords and ELSA performance. This extension supports annotating records with multiple keywords in trapdoor and record storage and enables the record to be returned with single keyword queries. In addition, the experiments demonstrated the scalability and efficiency of ELSA with an increasing number of keywords and complexity. Based on the experimental results and feedback received from the publication and presentation of this work, we published our third technical paper. In this paper, we improved ELSA by minimising the lookup table size and summarising the data records by integrating machine-learning (ML) methods suitable for execution at the edge. This integration removes records of unnecessary data by evaluating added value to further processing. This process results in the minimisation of the lookup table size, the cloud storage, and the network traffic, taking full advantage of the edge architecture benefits. We demonstrated the mini-ELSA expanded method on two well-known IIoT datasets. Our results reveal a reduction of storage requirements by > 21% while improving execution time by > 1.39× and search time by > 50% and maintaining an optimal balance between prediction accuracy and space reduction. In addition, we present the computational complexity analysis that reinforces these experimental results.

Despite more than twenty years of clinical experience since the first successful human hand transplant in 1998, the mechanisms underlying acute rejection in such vascularised composite allografts (VCAs) remain poorly understood. To further compound the problem, the reporting of patient data, treatment protocols, and definition of VCA rejection remains in constant flux. On the other hand, chronic rejection, which was previously thought to not affect VCAs, has now been accepted and recognised as both a reality and likely eventuality for VCA patients, with no realistic exit plan beyond re-transplantation currently. Between 2015 and 2017, I served as a post-doctoral research fellow at the VCA Laboratory of the Center for Transplantation Sciences, at the Massachusetts General Hospital (MGH), a teaching affiliate of Harvard Medical School in Boston, Massachusetts, USA to work on the development of immunologic tolerance protocols to VCA in both swine and non-human primate (NHP) pre-clinical VCA models. During this time, I was also a member of the clinical VCA service at MGH where I participated in the conduction of clinical VCA trials. I have maintained research collaborations with the same group since. Data from the International Registry of Hand and Composite Tissue Transplantation (IRHCTT) have shown that more than 85% of VCA patients develop at least one episode of acute VCA rejection within the first year, compared to approximately 10% of kidney transplant patients despite the use of highly similar clinical immunosuppression regimens. These differing observations led me to hypothesise that acute rejection might develop within the dermis, due to the vicinity of the subdermal plexus and abundance of skin immune cells, before presenting clinically on the surface of VCA skin. Therefore, this thesis is based on the enclosed publications which span the gamut of clinical, basic science and translational VCA research. By targeting VCA dermis, the primary objective is successful avertion of acute rejection, with the secondary objective of allowing mixed chimerism to develop following tolerance induction through delayed donor bone marrow transplantation (DBMT) in a NHP VCA model, based on clinical trials in renal transplantation patients at MGH that successfully achieved immunosuppression withdrawal. The first two papers (#1 and #2) in this thesis provide the clinical backdrop to the most pressing problems in VCA at present - acute and chronic rejection - for which we as a field still do not have definitive solutions to. Naturally, topical immunosuppression rapidly emerged as an attractive means of addressing acute rejection in VCA given the exteriorised skin component as compared to the typical, intra-abdominal location of solid organ transplant (SOT) allografts. It was theorised that such an approach would not only allow earlier identification and treatment of acute rejection, which presumably would reduce the risk of progression to chronic rejection, but also potentially allow a reduction in the overall immunosuppressive load. In turn, the risk of systemic complications to the VCA recipient would also be lowered. The above approach was explored in NHPs in the next two papers, initially inallogenic skin grafts (#3) (i.e. neovascularised) followed by VCAs, which are primarily vascularised (#4). Concurrently, ongoing research from the VCA Laboratory at MGH using a swine model suggested that rather than transient mixed chimerism (which was sufficient for renal transplantation), VCAs would require stable mixed chimerism instead. This could potentially be achieved through the DTIP approach which was successful in NHP lung transplantation at MGH. As well, analysis of swine VCA skin correlated remarkably well with MGH's clinical hand transplant patient following transplantation (#5). Therefore, the DTIP approach was trialed in a NHP VCA model next (#6) where chronological analysis of VCA skin both in the short- and long-term reflected our clinical observations (in Papers #1 and #2) but ultimately, tolerance was not achieved due to the persistence of acute rejection. With knowledge of results from #3 and #4, the topical approach was re-engineered for local immunosuppression delivery at the subcutaneous level through a collaboration with engineering colleagues from Rutgers University in New Jersey, USA. Subsequently, acute rejection was successfully mitigated when FK506-loaded discs were implanted subcutaneously during the VCA procedure, and mixed chimerism could be induced through DTIP using the same NHP VCA model. Further work is required however, due to the persistent, premature development of post-transplant lymphoproliferative disorder, which may be an experimental and/or NHP species-specific issue. Overall, this submission of seven papers has introduced the barriers in achieving tolerance to VCAs clinically, and described the laboratory efforts undertaken to reproduce, within ethical limits and animal welfare considerations, these immunological challenges in a robust, pre-clinical NHP VCA model. Most strikingly, the clinical observations and anticipated problems were accurately replicated in the NHP VCA studies. Potential mechanistic insight of acute rejection via VCA dermis was derived, and targeted through further studies to achieve successful proof-of-concept for the mitigation of acute rejection and ultimately, development of mixed chimerism.

A Systematic Review of the Criminal Offending Patterns Reported in the Last Two Decades for Young People with Neurodevelopmental Disorders: 2002-2022. Background: Neurodevelopmental disorders (NDDs) are highly prevalent in young offending populations compared to the general young population (Hughes et al., 2012). Less is known about the specific influence NDDs may have on frequency of offending, types of offending behaviour and how other factors impact on this relationship. Aim To systematically review, critically appraise and synthesise the available evidence on the relationship between NDDs and patterns of offending. Methods: ASSIA, CINAHL, MEDLINE and PsychINFO databases were searched for published studies that investigated the relationship between NDDs and offending. Observational, case-control or cohort studies from peer reviewed journals that explored the relationship between NDD and offending, included more than one NDD, utilised formal diagnoses, had an age range up to age 35 and were published between 2002 and 2022 were included in the review. Results: Ten eligible papers were identified and reviewed; two had low risk of bias. Prevalence rates of NDD in young offenders could not be conclusively established, due to the poor quality and different NDD and offending focuses between papers. Two low risk of bias papers found that ADHD featured in increased risk for violent offending. Conclusion: There is a link between NDD and offending in young people, particularly with certain NDDs. Quality of the evidence base requires refining and developing through more research to support young people with NDD who offend. Keywords: Juvenile, neurodevelopmental, offending, crime. Major Research Project The Impact of Head Injury and Neurodevelopmental Disorders on Frequency of Offending and Violent Offences in Young People. Background: Various impairments are associated with head injury (HI) and neurodevelopmental disorders (NDD), which are also risk factors for offending behaviour. Although rates of HI and NDD are high in adult prison populations, less is known about young forensic populations and the impact of HI or NDD on offending behaviours. Aims This study aimed to observe how well HI or NDD are reported on electronic health records and to investigate whether HI or NDD are related to increased frequency of offending, re-offending and violent offending. Methods: A retrospective, descriptive observational design using secondary data was employed. Data relating to risk assessment ratings and subsequent offending within a 6-month period from 76 young males, aged between 12-18, held by a Forensic Child and Adolescent Mental Health Service (FCAMHS) in Glasgow was used. Head injury and NDD was then extracted from electronic mental health records and combined with the FCAMHS data. Descriptive statistics described the sample and Fisher's Exact Tests investigated associations between HI, NDD and re-offending and HI, NDD and violent offending. Mann-Whitney U tests explored differences in number of offences between those with and without HI or NDD. Results: Head injury and NDD were common in the sample. There were no significant differences between HI or NDD and frequency of offending, reoffending and violent offending. There was a significant association between high levels of socio-economic deprivation and increased offending. Attention Deficit Hyperactivity Disorder was the most common diagnosis in the sample. Conclusions: No significant differences were found in frequency of offending, reoffending and violent offending between those with and without HI in this sample, although factors such as sampling and nature of information available in health records may have influenced this. The most common NDD diagnosis was ADHD and higher socio-economic deprivation was associated with reoffending. Further research in this area is required to inform clinical practice and service design.

Tablet devices, such as the iPad, have emerged among the most essential educational tools due to features that facilitate the learning and teaching process without the limitations of time or location. Tablet devices and their range of applications (apps) can potentially improve both the teaching and learning processes and the communication between teachers and students. However, there are concerns about the benefits of using tablet devices and their different apps in the learning process, including the extent to which students actually use them for educational purposes. Therefore, this study sought to evaluate the effectiveness of iPad usage, including various applications, in terms of improving students' mathematics achievement and motivation based on accomplishing the goals of mathematics lessons in a 10th grade secondary school in Saudi Arabia (SA). To achieve this, iPad devices were deliberately introduced to support teachers and students in the teaching and learning of mathematics. The study also sought to evaluate the impact that iPad usage and the various applications would have on mathematics teachers' perspectives regarding the teaching of mathematics concepts in the same secondary school in SA. While there are now many opportunities for technology to be used in the education sector, there is still a need for a better understanding of how and to what extent iPad devices and the various dedicated education apps can be integrated in teaching and learning in secondary schools in SA, particularly with regard to mathematics education. This is an important matter, as it has several wider implications for curriculum design, classroom practice, teacher and student education, and the development of greater understanding of learning and cognition in technology-enhanced learning settings. To generate insights into the effectiveness of introducing iPad devices and various apps related to teaching and learning mathematics in Saudi secondary schools, the study used a logical model design for program evaluation based on a mixed-method approach. A quasi-experimental design was applied as the primary quantitative approach, while the secondary qualitative approach was carried out simultaneously. The quasi-experimental period stretched over two months. In the first month, class A was the treatment group and pupils in that group used iPads and relevant apps to learn mathematics, while class B was the control group, with the pupils using traditional methods based on using books, paper, and pencils. The treatment was switched between the two classes in the second month. Data were collected from a pre-test and two post-tests (quantitative data), semi-structured interviews, and a focus group interview (qualitative data). The participants in this quasi-experimental study included 50 students from two classes in the 10th grade (25 participants in each class), as well as four teachers who took part in the interviews. The focus groups comprised eight groups of six students, four groups from each class. The quantitative data were analysed using a multi-statistical method in IBM SPSS and the qualitative data were analysed using thematic analysis. The study uncovered a wide range of evidence indicating encouraging results for the integration of the iPad and relevant applications in the process of teaching and learning mathematics in educational systems, particularly in Saudi Arabian secondary schools. The findings of the quantitative data showed that the iPad devices and the applications used significantly improved students' achievement in the period during which they were encouraged to use these devices to learn mathematics, with better results than when they used the traditional methods (books, paper, and pencils). However, this improvement might not occur if the students or teacher are not trained to use the device and the various educational apps employed in this quasi-experimental study. The findings of the students' focus group interviews revealed largely positive views towards the use of the iPad device and its apps, such as education platform apps and various communication apps. This device and its apps promoted students' performance in mathematics by providing immediate feedback, improving their mathematical skills, helping them to prepare for tests, and assisting them to search for information, thus equipping them with a better understanding of the content. The majority of students also found the use of these devices to be a source of motivation and they encouraged them to learn mathematics and achieve the goals of the lesson plans to a greater degree than when working with conventional methods. Moreover, the students were dependent on this device and its apps for their learning and viewed is as a useful and supportive educational tool for facilitating their communication and enhancing their collaboration, as well as organising their time and studies. However, while most of the students believed that the iPad and its apps encourage them to study mathematics, some students reported that they were not inclined to use this device to learn mathematics. They stated that their preference was to handwrite notes or complete mathematics activities using paper and pencil because they found it difficult to write certain symbols on the device. They also reported encountering several obstacles, such as interrupted or slow internet connection, low battery level, difficulty recharging the battery, some apps hanging during use, and the iPad screen breaking easily. The findings of the teacher interviews showed that, in general, the perception was that both teachers and students benefitted from the use of the iPad, and the apps were deemed useful tools for facilitating and improving the in-class teaching and learning processes. They believed that this device assisted them in achieving the lesson objectives faster than previous teaching methods. It also helped them to immediately ascertain their students' academic level, improve their students' performance, motivate their students to learn mathematics, and provide instant feedback for their students. The findings also demonstrate that iPads facilitated collaboration and communication among students, as well as developing their creativity, critical thinking, and self-reliance skills. However, the results also illustrated that there are several elements that make both teachers and students in SA public schools unwilling or unable to use the device and its apps. For instance, the infrastructure of schools may not be equipped to integrate the technology, especially so in the case of iPads. In addition, teachers were afraid to integrate iPad use in the classroom because they lacked the knowledge to use this device and its apps for educational purposes. They also faced continuing obstacles and limitations in using the iPad and its apps in the classroom environment. These obstacles were mainly associated with technical issues, such as lack of connection to the internet or battery problems. Other issues included students forgetting to bring their iPad device or using non-instructional apps in the classroom. The study, therefore, proposes some solutions to these obstacles, which could be beneficial for schools to consider before deciding whether to integrate iPad devices and their various apps in the classroom. Therefore, this study helps provide insights and evidence regarding iPad usage with various educational apps in the classroom. The implications of these findings are considered in relation to students' development, teachers' development, and the educational technology and school development curricula in SA secondary schools. Some suggestions regarding future research based on this are also offered.

Burden of disease studies can be used to summarise the combined impact that causes of morbidity and mortality have in a defined population in a manner that is consistent and comparable. They have become an increasingly popular means to use in knowledge exchange activities for informing national, and local, policy-making decisions. The Global Burden of Disease (GBD) study provide estimates on the burden of disease for each cause of disease and injury for individual countries, and sub-national areas for selected countries, which are adopted by many researchers and national public health institutes. Alternative national burden of disease studies exist, independent of the GBD study, which utilise country-specific data sources that are representative of the state of health in their country. The co-existence of these studies can potentially be problematic for knowledge exchange activities, particularly when estimates differ and neither party are able to explain why the differences exist. This can often lead to speculation on why the differences occur, and the monopolisation of burden of disease research by the GBD study can often be problematic in ensuring a balanced narrative emerges. Many users often just seek to appraise differences in the input data as they often lack the experience, or will, to understand methodological processes as they are often complex and exhaustive. However, these differences in methods could plausibly play a key contribution in explaining differences in results. Two such methodological choices are in relation to the choice of severity distribution in assessing the non-fatal burden of disease, and the choice of standard population that is used when estimating standardised rates. These issues are tackled in the first part of this thesis. The impact of these methodological choices were appraised using approaches from the Scottish Burden of Disease study, relative to those of the GBD study. The first aim of this thesis is to establish whether using standard GBD study severity distributions result in major differences, compared to using severity distributions that better reflect the epidemiological situation in Scotland using the example of individual cancer types. The second aim of this thesis is to determine whether using different standard populations to standardise rates leads to major differences in how causes of disease and injury are ranked using disability-adjusted life years (DALYs). The research presented in this thesis gives insights into how impactful seemingly slight methodological choices can result in major differences. The second subset of research questions relate to establishing methods for COVID-19 burden of disease assessment, and monitoring the burden of COVID-19 using DALYs. The aims of this work presented in this thesis were to: (i) Assess which European countries were likely to be most vulnerable to severe outcomes from COVID-19; (ii) Develop an international consensus method for estimating COVID-19 DALYs; (iii) Estimate COVID-19 DALYs in Scotland during 2020 and contextualise the result compared to the leading pre-pandemic causes of disease; (iv) Estimate the extent of inequality in COVID-19 DALYs in Scotland during 2020; (v) Provide an alternative way of assessing the impact of all-cause inequalities by comparing inequality-attributable DALYs to the impact of COVID-19; (vi) Monitor changes in the fatal COVID-19 burden of disease in 2021, in the context of vaccine availability, compared to 2020. The research questions posed in this thesis are investigated in the included seven firstauthor papers. The insights from each of the papers are synthesised in an explanatory essay. This essay attempts to show the impact of each of the individual papers, and how they form a cohesive body of work that enhances the understanding and application of methods for use in burden of disease assessment. The explanatory essay presents a two-tier approach. The first part considers the impact of: (i) severity distributions; and, (ii) standard populations in age-standardised rate calculations, in burden of disease assessment. The essay discusses the importance of the findings from the included papers. It also highlights their importance for other stakeholders in international burden of disease research networks', given the impact of severity distributions on resulting estimates is now more widely understood. The second part of the explanatory essay focuses on developing consensus methods to estimate COVID-19 DALYs, and then focuses on their application in monitoring the overall, and inequalities in the, COVID-19 burden of disease in Scotland. The need for a consensus method is justified on the basis of ensuring that the comparative properties of DALYs remain. This work has synergies with the first part of the explanatory essay, as it is important that assessments are reflective of the best available country-specific data inputs. The significance of this work is discussed through its uptake within the international research community. The rationale for undertaking burden of disease assessments it to generate comparable estimates for where risk factors, causes of death, disease and injury are causing the largest public health losses. In doing this, it provides compelling evidence to inform resource allocation discussions for tackling population health needs, and the implications for which these needs will have in ensuring care services and workforces are proportionate to the challenge. Through presenting developments and the journey through these seven published works in included in this thesis, I aim to have demonstrated the importance of the work in enhancing the understanding and application of burden of disease assessment methods. It is vital that the methodological context, and any uncertainties for which estimates are produced in, is well understood.

The aim of this dissertation is to provide a comprehensive and novel approach to the study of monopoly in general equilibrium. First, a foundational paper is provided, in which we define a concept of monopoly equilibrium within a bilateral exchange market a la Shitovitz, in which an atomic monopolist, that owns the totality of one commodity, faces an ocean of small traders (also called the atomless part of the economy), that owns another commodity. A monopoly equilibrium is defined as a quantity offered by the monopolist that maximizes her utility, given a price selection induces by her offers. After defining the notion of equilibrium, we provide parallels with the standard notions in partial equilibrium, under further assumptions on the structure of the demand function of the atomless sector for the good owned by the monopolist, namely its invertibility and differentiability. In particular, under the differentiability assumptions, we show that an interior monopoly equilibrium lies at the tangency point between the monopolists' indifference curve and the small traders' offer curve. Once the notion of a monopoly equilibrium is established, the first follow up for the analysis is a game theoretic foundation for such an equilibrium. Following the work of Busetto et al. (2011), and recognizing the two stage flavour of the definition of a monopoly equilibrium, we provide a theorem that states the equivalence between the set of monopoly equilibrium and set of subgame perfect equilibria. Next, to show the concept of monopoly equilibrium holds non vacuously, I proceed to study the existence properties of such equilibrium. Non existence examples in which small traders have CES utility functions are provided and a link between the existence of an equilibrium and the degree of substitutability of the goods is explored. Therefore, the existence result is proved by introducing a sufficient assumption on the utilities of the small traders, stressing that they need to be locally equivalent to CES utility functions whose elasticity is larger than unity. Finally, an analysis of the optimality of such equilibrium is explored. In particular, drawing from Aumann seminal's paper on advantageous monopolies, we show how our model (under mild assumptions) is able to rule out the unintuitive situation of a monopolist being better off by being competitive. In particular, we show that a monopolist can be walrasian, i.e. the monoply equilibrium might coincide with a competitive equilibrium, and we characterize this equivalence proving that this only occurs whenever the monopolist optimal bid coincided with her endowment. However, whenever the set of monopoly equilibria and the set of competitive equilibria are disjoint, then the monopolist is always better off at a monopoly equilibrium and the small traders are exploited, i.e. their utility is always lower at a monopoly equilibrium with respect to a competitive equilibrium.

The four publications included in this thesis embody a programme of research aimed at improving interpretations of informed consent to medical treatment in the United Kingdom (UK). Paper one considers the application of solidarity - often a concept associated with political debate - to bioethical issues. It examines leading conceptualisations of solidarity in healthcare and their relation to the practitioner-patient dynamic and standards of informed consent. In considering the interplay between ethical principles of solidarity and autonomy, the paper explains how current concepts of healthcare solidarity may undermine individual patient autonomy by creating imbalance in the practitioner-patient dynamic. Current constructs of solidarity are also considered to be exclusionary which, it is argued, may potentially lead to the othering of patients. The effects of patient exclusion and othering are examined in paper one and throughout the subsequent papers. In response to these issues, the novel concept of 'conjoint solidarity' is presented in contribution to the existing scholarship. It calls upon healthcare stakeholders (incorporating healthcare practitioners and patients) to adopt a duty to assist in the identification and achievement of improved healthcare outcomes. By recognising the epistemic value of both practitioners and patients, conjoint solidarity is said to promote an inclusive form of solidarity that promotes balance in the practitioner-patient dynamic and that will support, rather than undermine, autonomy. It is anticipated that by facilitating greater patient involvement in the decision-making process, trust can be rebuilt, and healthcare outcomes improved. From this ethical grounding, informed consent is explored through the subsequent three papers which address deficiencies in current interpretations of the legal standard for informed consent and propose new ways in which shared decision-making can be enhanced to mitigate against the kind of harms which have been witnessed in recent years. Paper two explores the evolution of the legal standard of informed consent to medical treatment in the UK. It examines the development of the judicial precedence pertaining to informed consent through key cases such as Bolam v Friern Hospital Management Committee [1957], Sidaway v Board of Governors [1985], Bolitho v City and Hackney HA [1998], and Montgomery v Lanarkshire [2015]. Comparative analyses are drawn between concepts such as 'significant' and 'material' risk, and between the 'reasonable person' and 'particular patient' standards. It is argued that the legal interpretation of material risk is broad, and that patterns of judicial reasoning are suggestive of a move towards recognition of majority views on reasonableness. The paper describes how financial interests can influence healthcare practitioners to the extent that their practice may be harmful to the patient and, therefore, concludes that potent financial interests - namely those likely to have greatest impact upon patterns of practice - may be interpreted as disclosable material risks under existing common law standards. Paper three examines standards of informed consent in relation to the issues surrounding the use of pelvic (vaginal) mesh - as detailed in the 2020 Cumberlege Report - and questions whether improved interpretations of the informed consent process could mitigate against future harms. It is recognised that treatment selection - which remains a matter of professional judgement according to Bolam v Friern Hospital Management Committee [1956] - could be deemed exclusionary towards patients. Drawing on the concept of conjoint solidarity, it is suggested that patient-based evidence should be afforded greater consideration as part of evidence-based practice to promote a more inclusive healthcare system which affords greater recognition to the epistemic value of the patient to enhance overall shared decision-making. The concept of risk disclosure is also re-examined in relation to medical device implantation, and it is recommended that the long-term risks deriving from implantable devices, or indeed unknown risks associated with innovative treatment proposals, be deemed disclosable. In this way, patient autonomy can be upheld so that patients are afforded the opportunity to decide whether, or not, to incur such risk. Paper four considers how the process of shared decision-making, which precedes informed consent, can be enhanced by facilitating active discussion [4]. In returning to the concept of relational autonomy, persuasion is presented as a means of promoting greater patient-practitioner dialogue and engagement which can allow patients to question and explore the information that is presented. The example of vaccine hesitancy is used to describe the ways in which the informed consent process can be used to tackle misinformation and promote confidence in medical treatments. The standard set out in Montgomery requires that patients be informed of benefits, material risks and reasonable treatment alternatives when consenting to medical treatment. On these grounds, it is suggested that informing patients of the benefits of vaccination could be a means of addressing misinformation. Threads of conjoint solidarity also run through the argument as it is suggested that disclosure of vaccination benefits, should relate to both the individual and collective benefits in terms of individual and herd immunity. This example is particularly reflective of the bridge which exists between relational autonomy and conjoint solidarity. The thesis then explores risks and expands upon the disclosure of 'individual risk'. It is suggested that risk of not vaccinating also be disclosed - both in terms of the risk of disease posed to individual and the most vulnerable in society. Persuasion is employed, not as a means of coercion, rather as a means of engagement to ensure patients understand the information provided which may also help to address misinformation. Similarly, the patient is afforded the opportunity to 'persuade' the practitioner to understand their perspective, which is a departure from traditional models of the practitioner-patient relationship. In presenting this work three key themes emerge: deficiencies in shared decision making arising from the practitioner-patient relationship, analysis of informed consent and its deficiencies, and proposals for improving interpretations of informed consent to ensure patients are engaged and informed. It is anticipated that the proposed recommendations will have utility for rebuilding patient trust and to enhance patient involvement to mitigate against recurrences of harms seen in the past.

Nuclear mean-field models [1] are highly successful in describing a wide range of properties of atomic nuclei, including their structure, binding energies, and the spins and parities of their quantum states. However, by their very nature, mean-field models cannot account for the effects of residual two- and three-body forces between nucleons. In particular they over-predict the measured occupancy of valence nucleon orbits in a wide range of nuclei and under-predict the occupancies of states above the Fermi surface [2]. It has long been thought that this transfer of occupation from valence to higher-lying energy levels may be due to interactions, or correlations, between nucleons, which are not described by mean-field models. The electromagnetic interaction is well understood [3]. Hence electron and photon probes provide an excellent means of studying the internal structure of nuclei and the interactions between nucleons. This thesis describes an extensive programme of photon- and electron-induced experiments, most of which were led by the author, which studied the ejection of two, or three, correlated nucleons from atomic nuclei, in order to deduce information about the interactions between them. This work was carried out over a period of many years, primarily at the electron Microtron facility (MAMI) of the University of Mainz, Germany [4]. The author was assisted in this work by six Research Associates and ten Research Students working on different aspects of the programme. A wide range of experiments was carried out on several light nuclei: 3He, 4He, 6Li, 12C and 16O. Real photon experiments used the tagged-photon technique [A1] to measure the energy of incident photons. Many different aspects of two-nucleon emission reactions were studied, including their photon energy dependence, missing energy dependence, recoil momentum dependence, angular dependence, dependence on kinematic conditions, isospin dependence and their dependence on photon linear polarisation. The work was extended to study the contribution of three-body interactions in 3He and 12C by looking at the simultaneous emission of three nucleons from light nuclei, as well as the emission of proton-deuteron pairs. Collaborations were formed with nuclear theoreticians working in Valencia, Ghent and Pavia in order to provide a detailed interpretation of the data obtained. This involved filtering the predictions of theory calculations through the physical acceptance of the experimental apparatus to allow meaningful comparisons with measured observables. The author joined the CLAS collaboration at the Jefferson Lab 6.0 GeV electron accelerator at Newport News, Virginia, USA in 2009. The Jefferson Lab facilities allowed nucleon-nucleon correlations to be studied with higher energy probes, permitting electron scattering measurements to be carried out at large values of fourmomentum transfer and at values of Bjoerken-x greater than 1. This latter condition explicitly requires the participation of more than one nucleon. Several key results from this work have advanced our understanding of nucleon-nucleon correlations. The previously-noted strong isospin dependence of nucleon-nucleon correlations was observed to persist at higher energies, even though the detailed mechanisms evolve with energy transfer. In addition, the strong observed charge dependence of the highmomentum fraction of nucleons within the nucleus has been related to the isospin dependence of the correlations. Finally, evidence has been found which supports a connection between short-range correlations (SRC) and the "EMC effect", in which the structure function for Deep Inelastic Scattering (DIS) of leptons on nucleons in heavy nuclei is strongly suppressed compared to the same reaction in light nuclei. The author led the programme of two- and three-nucleon emission studies at Mainz from the mid-1980s onwards, writing and presenting seven experiment proposals [5-11] which were approved by the Mainz International Programme Advisory Committee. These proposals provide a strong rationale for undertaking these investigations. Throughout his Mainz work, the author worked closely with academic colleagues from the University of Glasgow, as well as physicists from Mainz, Edinburgh and Tübingen. The Glasgow research group designed, constructed, tested and subsequently upgraded, two tagged photon spectrometers which underpinned and enabled the photon-induced experiments described in this thesis. The author took responsibility for the design, production, installation and testing of two "trigger" proton detector hodoscopes. The first detector array was used in experiments at photon energies up to 180 MeV, while the second was used in experiments at higher energies. Correlated neutrons and protons were detected in a separate "time-of-flight" scintillation detector array [12], developed jointly by physicists from Glasgow and Tübingen universities. The author directed the analysis of the majority of the data obtained from the experiments at Mainz, while other Glasgow research staff developed data collection and analysis software. Colleagues from Tübingen, Mainz and Edinburgh contributed cryogenic targets and analysed the data from the remaining experiments. The author's work on equipment development is detailed in section A of this thesis. The author contributed to the design, installation and testing of the initial tagged photon spectrometer at the Mainz laboratory, before leading the development and production of two detector hodoscopes used to detect protons from photon-induced reactions. He also made contributions to studies of diamond radiators which were used to produce linearly polarised photons used in some of the later experiments. Section B forms the central part of this thesis. The papers in this section describe the results and interpretation of an extended programme of two- and three-nucleon emission reaction studies carried out at Mainz under the leadership of the author. In addition to directing the experimental work, the author led the drafting, revision and production of the majority of the papers in this section. He initiated close working relationships with three different groups of theoretical physicists in order to carry out calculations to interpret the experimental data. Some of these theoreticians are coauthors on particular papers. The papers in Section C report results from a small number of selected experiments at the higher energy 6.0 GeV Jefferson Laboratory electron accelerator. This work provides valuable additional insight into correlations between nucleons in atomic nuclei and shows how this field has developed with the availability of higher energy electromagnetic probes. The author was co-investigator on a major Jefferson Lab grant [13] which laid the foundations for the analyses reported in this section. Section D contains a recent conference review paper by the author which provides a concise and succinct summary of the most important work included in this thesis.

Although chronological age is the main determinant of ageing, physical and social environment factors play a crucial role in healthy ageing, even in earlier stages of life. Physical and biological limitations are not, necessarily, restricted to older ages. Therefore, considering the predicted rapid increase in the number of older people worldwide along with its individual and societal burden, research into healthy ageing - including middle-aged and older individuals - is a priority. Physical capability is the ability to perform the basic and instrumental activities of daily living. As the decline in physical function occurs progressively with age, the study of this process should start earlier in life and not only during older age. Low levels of physical capability markers (such as grip strength, muscle mass and physical performance [gait speed]) are strong predictors of future health, including premature mortality, cardiovascular and neurodegenerative diseases in middle-aged and old-aged populations. With age, the decline in physical function could occur in more than one marker. Consequently, the study of combined physical capability markers and their clinical combinations 'sarcopenia' and 'frailty' needs to be further explored using prospective data with common and non-common adverse health outcomes. Considering the associations of physical capability, sarcopenia, and frailty with adverse health outcomes are not fully understood (both investigated in isolation and as the combined effect), the main aim of this thesis was to determine the associations between measures of physical capability, sarcopenia, and frailty and a range of health outcomes, including mortality, cardiovascular (CVD) and respiratory diseases. To achieve this general aim, seven papers were completed and included in this thesis. Since the overall prevalence of frailty was already estimated using different classifications, the first paper included in this thesis systematically reports and summarises the overall prevalence of sarcopenia (and severe sarcopenia) using different global classifications. Using 6 main classifications, I estimated that the overall prevalence of sarcopenia ranges from 10% to 27% according to the classification used while the prevalence of severe sarcopenia ranges to 2 to 9%. Then, data from the UK Biobank study was used to investigate the association between the exposures and health outcomes. UK Biobank is a general cohort study that recruited over 500,000 participants between 2006 and 2010. Participants aged 37-73 years attended one of the 22 assessment research centres across Scotland, England and Wales at baseline. Using the UK Biobank data, the other six studies were carried out. Across these manuscripts, the associations between different exposures - combinations of sarcopenia, frailty, and individual physical capabilities - and adverse outcomes were determined in each manuscript included: incident and mortality for CVD, respiratory diseases, osteoporosis, cancer, COVID-19, dementia as well as all-cause mortality. In terms of individuals physical capability markers, the strongest association was identified between slow gait speed and incident COPD and respiratory disease as well as all-cause, respiratory and CVD. For incident osteoporosis instead, low muscle mass, followed by slow gait speed, were associated with a higher risk in both sexes. Regarding combinations of physical capability markers, slow gait speed plus low muscle mass, followed for severe sarcopenia, demonstrated the strongest association with incident respiratory disease and all-cause mortality. In terms of osteoporosis, pre-sarcopenic men and sarcopenic women showed a stronger association with incident osteoporosis. The study of the combination between frailty and sarcopenia categories identified that the highest CVD and respiratory risk was identified among frail and sarcopenic individuals. In addition, individuals with more than one clinical condition (frailty, sarcopenia, cachexia, and malnutrition) had almost five times higher risk of dying than those with none (hazard ratio (HR): 4.96 [95% CI: 2.73 to 9.01]). Finally, when frailty was investigated in isolation, I demonstrated that, independently of the frailty classification used, those with pre-frail or frail had a higher risk of severe covid-19. Moreover, pre-frail and frail individuals had an increased risk of all-cause dementia independently of confounder factors such as morbidity (HR pre-frail: 1.21 [95% CI: 1.04 to 1.42] and HR frail: 1.98 [95% CI: 1.47 to 2.67]). Therefore, this thesis demonstrated that individuals with lower physical capability, sarcopenia and/or frailty had a higher risk of adverse health outcomes, including: incidence and mortality for osteoporosis, CVD, respiratory disease, cancer, COVID-19, dementia, and all-cause mortality. These associations remained even after adjustment for a large range of potential confounders and existed both in middle-aged and older adult sub-groups. Considering that the age-related decline in physical capability markers, and therefore sarcopenia and frailty, could be delay and prevented, health interventions to improve physical capability that may reduce the risk of these outcomes are more urgent than ever.

The papers presented in this submission contribute to our understanding of a significantly under-researched specialism within the accountancy profession, namely that of insolvency. Beyond illustrating the complexity and multidisciplinary nature of the profession's expert knowledge systems, the papers illustrate how this knowledge is applied in practice in the interpretation and application of insolvency law. In turn, this reveals the significant economic, social and political reach of accounting professional labour through specialised service lines and the potential value of professional work to the state in governing the economy and society. This includes facilitating an efficient exit framework for corporate failure, processing significant numbers of personal bankruptcies, redistributing economic loss amongst society, and reallocating resources to new (productive) uses. The papers explore the effects or consequences of professional judgement, expert opinion and the application of moral authority in policy interpretation, evaluation of outcomes and in phases of statutory reform. They also show how accounting and financial information is mobilised to build trust in crisis management contexts and the 'desirable' properties of accounting information in this regard. Combined with an understanding of the profession's expert knowledge base, the papers show the extent to which the profession is trusted to implement state policy and the potential of accounting information to act as both a trust-building and accountability mechanism between the professionals and the range of private and public interests affected by insolvency. Through an interpretive approach, accounting as a social science, is studied with contextualised understandings of the individual and institutional players on the field. The identification of trust-based relationships in the insolvency profession direct attention towards the existence of professional networks and the evolutionary strategies that the profession engages in to ensure individual, firm and professional survival. In turn, this encourages academic reflection on how we might view the 'accountancy profession' and therefore also on novel research agendas.

This thesis contributes to single-image reconstruction under visual disruption caused by rain in the following areas: 1. Parameterization of a Convolutional Autoencoder (CAE) for small images [1] 2. Generation of a rain-free image using Cycle-Consistent Generative Adversarial Network (CycleGAN) [2] 3. Rain removal across spatial frequencies using the Multi-Scale CycleGANs (MS-CycleGANs) 4. Rain removal at spatial frequency's sub-bands using theWavelet-CycleGANs (W-CycleGANs) Image reconstruction or restoration refers to reproducing a clean or disruption-free image from an original image corrupted with some form of noise or unwanted disturbance. The goal of image reconstruction is to remove such disruption from the original corrupted image while preserving the original detail of the image scene. In recent years, deep learning techniques have been proposed for removal of rain disruption, or rain removal. They were devised using the Convolutional Neural Network (CNN) [3], and a more recent type of deep learning network called the Generative Adversarial Network (GAN) [4]. Current state-of the-art deep learning rain removal method, called the Image De-raining Conditional Generative Adversarial Network (ID-CGAN) [5], has been shown to be unable to remove rain disruption completely, or preserving the original scene detail [2]. The focus of this research is to remove rain corruption from images without sacrificing the content of the scene, starting from the collection of real rain images to the testing methodologies developed for our Generative Adversarial Network (GAN) networks. This image rain removal or reconstruction research area has attracted much interest in the past decade as it forms an important aspect of outdoor vision systems where many computer vision algorithms could be affected by rain disruption, especially if only a single image is captured. The first contribution of this thesis in the area of image reconstruction or restoration is the parameterization of a Convolutional Autoencoder (CAE). A framework for deriving an optimum set of CAE parameters for the reconstruction of small input images based on the standard Modified National Institute of Standards and Technology (MNIST) and Street View House Numbers (SVHN) data sets are proposed, using the quantitative mean squared error (MSE) and the qualitative 2Ds' visualization of the neurons' activation statistics and entropy at the hidden layers of the CAE. This methodology's results show that for small 32x32 pixels' input images, having 2560 neurons at the hidden layer (bottleneck layer) and 32 convolutional feature maps can result in optimum reconstruction performance or good representations of the input image in the latent space for the CAE [1]. The second contribution of this thesis is the generation of a rain-free image using the proposed CycleGAN [2]. Its network model was trained on the same set of 700 rain and rainfree image-pairs used by the recent ID-CGAN work [5]. In the ID-CGAN paper, there was a thorough comparison with other existing techniques like sparse dictionary-based method, convolutional-coding based method, etc. The results using synthetic rain training images have shown that the ID-CGAN method has outperformed all other existing techniques. Hence, our first proposed algorithm, the CycleGAN, is only compared to the ID-CGAN, using the same set of real rain images provided by the authors. The CycleGAN is a practical image's style transfer approach that falls into the unpaired category, which is capable of transferring an image with rain to an image that is rain-free, without the use of training image-pairs. This is important as natural or real rain images don't have their corresponding image-pairs that are rain-free. For comparison purpose, a real rain image data set was created. The real rain's physical properties and phenomena [6] were used to streamline our testing conditions into five broad types of real rain disruption. This testing methodology covers most of the different outdoor rain distortion scenarios captured in the real rain image data set. Hence, we can compare both ID-CGAN and CycleGAN networks using only real rain images. The comparison results using both real and synthetic rain has shown that the CycleGAN method has outperformed the ID-CGAN which represents the state-of-the-art techniques for rain removal [2]. The Natural Image Quality Evaluator (NIQE) is also introduced as a quantitative measure [7] to analyze rain removal results as it can predict the quality of an image without relying on any prior knowledge of the image's distortions. The results are presented in Chapter 6. Subsequently, from the CycleGAN technique, the third contribution of the thesis is proposed based on the multi-scale representation of the CycleGAN, called the MS-CycleGANs technique. This proposed technique was built on the remaining gaps on rain removal using the CycleGAN. As highlighted in the rain removal paper using CycleGAN [2], the CycleGAN results could be further improved as its reconstructed output was still unable to remove the rain components at low frequency band and preserved as much original details of the scenes as possible. Hence, the MS-CycleGANs was introduced as a better algorithm than the CycleGAN, as it could train multiple CycleGANs to remove rain components at different spatial frequency bands. The implementation of the MS-CycleGANs is discussed after the CycleGAN, and its rain removal results are also compared to the CycleGAN. The results of the MS-CycleGANs framework has shown that the MS-CycleGANs can learn the characteristics between the rain and rain-free domain at different spatial frequency scales, which is essential for removing the individual frequency components of rain while preserving the scene details. In the final contribution towards image reconstruction for removal of visual disruptions caused by rain across spatial frequency's sub-bands, the W-CycleGANs is proposed and implemented to exploit the properties of wavelet transform such as orthogonality and signal localization, to improve the CycleGAN results. For a fair comparison with the CycleGAN, both the proposed multi-scale representations of CycleGAN networks, namely the MS-CycleGANs and the W-CycleGANs, were trained and tested on the same set of rain images used by the ID-CGAN work [5]. A qualitative visual comparison of rain-removed images, especially at the enlarged rain-removed regions, is performed for the ID-CGAN, CycleGAN, MS-CycleGANs and W-CycleGANs. The comparison results among them has demonstrated the superiority of both the MS-CycleGANs and W-CycleGANs in removing rain distortions.

Introduction: There has been an increased focus over the past thirty years on recognising and responding to trauma. This has led to a shift towards developing trauma-informed policies and approaches across service settings, systems and jurisdictions in Western counties. Trauma Informed Care (TIC) has been found to improve service user experiences, enhance working relationships for staff and increase job satisfaction. This review aimed to synthesise stakeholders' perspectives on the implementation of TIC across public services, as well as identifying barriers and facilitators. Method: Six databases (EMBASE, PubMed (MEDLINE), PsycArticles, PsycINFO, Scopus and Sociological Abstracts) were electronically searched in September 2020. Reference lists were searched, and forward citation searches were conducted on the included papers. Results were analysed utilising best-fit framework synthesis, using the NHS Education for Scotland TIC framework. Results: 1589 records were screened, and twelve papers were eligible for inclusion in the review and quality appraisal. Synthesis identified that stakeholders' perspectives were captured by the TIC principles of safety, trust, collaboration, choice and empowerment. Multi-level community and systemic barriers were identified, including a lack of support for staff and vicarious trauma. Positive relationships, leadership, a commitment to long-term training and staff support were highlighted as key facilitators of TIC across services. 10 Conclusions: Stakeholders' perspectives reflected the principles of TIC, with individuals relating their experiences to the five core principles outlined above. Complex interacting factors were highlighted, including how professionals' prior training and systemic stressors can contradict a trauma-informed approach. Further research into TIC is needed, particularly focusing on client perspectives, TIC applied to staff and experiences of TIC across diverse cultures.

Background: Traumatic Brain Injury (TBI) early in life is common. Where recovery is poor, TBI can adversely impact typical brain development and function, and increase the risk of offending. Aim To systematically review the evidence for a relationship between TBI early in life and offending, with specific consideration of the effects of age at injury and injury severity. Methods: To identify relevant papers, electronic database searches (CINIHAL, PsycInfo, MEDLINE, EMBASE) were carried out using relevant search terms. Reference lists from included articles were also hand searched. The papers were assessed for risk of bias using set criteria. Some papers were co-rated by an independent person. Results: Twenty-one articles were included. Articles rated as low bias provided evidence to suggest that TBI before the age of 26 is associated with increased risk of offending, particularly violent offending, where TBI occurs after the age of 6 or 12 and is more severe. Potential mediators associated with executive function such as self-control and temperament, were identified. Conclusions: Whilst there was some evidence to suggest TBI before age 26 increases offending risk, limitations and bias in studies indicates a need for further good quality research.

Introduction: It has been established that economic hardship can influence parental adjustment and coping as well as child wellbeing. We review evidence for a relationship between exposure to the Great Recession (2007-2009) and increases in the incidence of reported child maltreatment. We aimed to develop insights from this earlier economic crisis that may be instructive in recovery planning from the Covid-19 global pandemic, which has caused a significant global economic crisis. Methods: A literature search was conducted using the MEDLINE, EMBASE, PsychINFO, and Web of Science Core Collection databases. Keyword and MeSH searches were completed to identify relevant articles. Inclusion criteria and risk of bias were assessed by two blinded reviewers. Result: From 607 reports screened for eligibility, 11 papers were included in the final qualitative synthesis and quality assessment. We found limited evidence that young people faced an increased risk of maltreatment between 2007 and 2009, especially when compared to maltreatment rates before 2007. However, although the reviewed papers were of acceptable quality, generalisability was constrained due to heterogeneity in methods and outcome measures between reviewed articles. Conclusion: Despite the currently limited evidence that child maltreatment increases during periods of deep economic recession, it is important that societies act to protect the welfare of children and young people during these challenging periods.

Chapter 1: Service-Related Experiences of Gay and Lesbian Carers of People Living with Dementia: A Systematic Review. Introduction: Evidence suggests that lesbian, gay, bisexual, transgender, queer + (LGBTQ+) adults experience difficulties accessing person-centred health and social care. Experiences of social exclusion may place additional strain on LGBTQ+ carers compared to heterosexual or cisgender counterparts and intersect further with the stigma of dementia. This review aimed to synthesise service-related experiences of LGBTQ+ carers of people living with dementia. Method: Seven electronic databases were systematically searched. Two journals were hand-searched. Reference list and forward citation searches were conducted on included papers. Results: 325 records were screened. A total of 10 papers were eligible for thematic synthesis and quality appraisal. Only gay and lesbian carers were represented in included studies. Synthesis identified three central themes: 'Intersecting forms of discrimination', '(Loss of) control over the disclosure process' and 'Diverse support needs and preferences.' Conclusions: Intersecting forms of discrimination, including explicit homophobia and implicit heteronormativity, can increase burden on gay and lesbian carers of people living with dementia. Control over the disclosure process is important to many carers but can be lost as the cared for person's dementia progresses. Gay and lesbian carers have diverse support needs and preferences, indicating service development is needed to provide safe and inclusive spaces. Further research is required to enrich understanding in this area and should include racially, culturally and socially diverse (LG)BTQ+ carers of people living with dementia. Chapter 2: Experiences of Divorced Women Living in Palestine: A Mixed-Method Narrative Analysis. Introduction: Research involving divorced Palestinian women is limited. Previous studies found some women seek divorce due to domestic abuse and lack of autonomy, and that previous generations experienced social exclusion. This cross-cultural secondary analysis aimed to understand how divorce changes the lives and psychological wellbeing of contemporary Palestinian women, how intersecting identities might influence change, and to recommend areas of Palestinian research development for traditionally marginalised groups. Method: A single-case narrative was developed from a translated transcript, and common themes were compared with quantitative data from a sample of 93 divorced women assessed with a survey designed by local clinicians. Results: In the single-case narrative, divorce represented freedom from a "prison-like" marriage and a chance for personal development. Half of the broader sample shared experiences of abusive marriages and most anticipated more freedom following divorce. Differences in age, place of residence and educational level were considered. Conclusions: Divorce can improve the lives of Palestinian women and provide opportunities for wellbeing and personal growth. However, post-divorce experience may vary depending on age, family support, living situation and educational level. Palestinian researchers are encouraged to enrich understanding in this area by developing methodologies relevant to the sociocultural and political context.

Aims and Objectives:To systematically review factors influencing anxiety and depression in implantable cardioverter defibrillator (ICD) recipients. Background: An ICD is a device used to prevent life-threatening ventricular arrhythmias. While the ICD is accepted by most recipients: a considerable number of patients experience distress following implant. The socio-demographic, clinical, ICD- specific and psychosocial factors associated with distress in ICD-recipients has received increasing attention. Methods:Six electronic databases (Applied Social Science Index and Abstract, CINAHL, EMBASE, Medline, Psychology and Behavioral Sciences Collection and PsycINFO) were searched on the 24/07/2020. Additional papers were identified by hand searching relevant journals, forward citation searching and reviewing the reference lists of included studies. This review was limited to studies on adult patients who received a transvenous or automatic ICD or ICD with cardiac resynchronisation therapy for primary or secondary prevention purposes. Other inclusion criteria were peer reviewed quantitative papers published in English from January 2014 to July 2020, which examined factors influencing anxiety and depression. The quality of the papers was rated using the Crowe Critical Appraisal Tool. Results: Anxiety and depression were linked to socio-demographic factors (female sex, younger age, living alone), clinical factors (heart failure, coronary heart-disease or history of emotional distress/psychotropic medication use), ICD-specific factors (elevated ICD-related concerns, low ICD knowledge, negative treatment expectations), and psychosocial factors (avoidance, perceived control, Type D personality and optimism). Conclusions: All papers suffered from methodological limitations and the findings should be interpreted with caution. Future research employing prospective longitudinal designs with controls for confounding factors is required to understand the relationship between socio-demographic, clinical, ICD-specific and psychosocial factors and distress in ICD-recipients over time. Relevance to clinical practice: Results demonstrated a relationship between elevated ICD-related concerns and increased distress in ICD-recipients. Routine screening for ICD-related concerns may identify patients at risk of anxiety and depression post ICD- implant. Aims and Objectives: To describe the trajectory of anxiety and depression in Chronic Heart Failure (CHF) patients during 12-month follow-up and to identify characteristics independently associated with anxiety and depression. Background: CHF patients with depression and anxiety are at increased risk of poorer outcomes including hospital readmission. There is limited research describing the trajectories of anxiety and depression in CHF patients over time. Design: The study was a secondary analysis of data collected in a longitudinal study investigating the palliative care needs of 272 CHF patients in Glasgow. Methods: Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS) at baseline and every four-months. Results: From baseline to 12-months, there was a significant reduction in the proportion of CHF patients reporting symptoms of anxiety (43.5% vs 25%) and depression (40% vs 27.4%). Looking at change in HADS scores over 12-months, 54.3% of patients were free of significant anxiety at all assessments, 21.7% showed an improvement in initially distressing anxiety, and 2.2% developed anxiety as the study progressed. Based on change in HADS depression scores across 12-months, 53.7% did not report significant depression, 18.9% experienced resolution of depression symptoms, and 6.3% went on to develop depression as the study progressed. One in five patients experienced persistent anxiety and depression throughout. In regression analysis, baseline anxiety, health- related quality of life, history of depression and female sex emerged as predictors of anxiety, while baseline depression, history of depression, antidepressant medication use, and female sex predicted depression. Conclusions: Results suggest a significant reduction in the proportion of CHF patients reporting clinically significant anxiety and depression from baseline to 12-month follow- up. Although there was a subset of participants that experienced persistent symptoms of anxiety and depression. Relevance to Clinical Practice: Routine screening for anxiety and depression in CHF patients is recommended.

Key points • This thesis aimed to develop a framework to help people undertaking health technology assessment of health technologies in development (termed 'analysts') approach their work. • It used a literature review and learning from five case studies to develop a framework which described the features of this type of health technology assessment, a generic process for undertaking the work and described which methods might be appropriate. Although the case studies are all diagnostic technologies, the framework would be appropriate for those working with small and medium-sized developers of any type of health technology. • Analysts need to be aware that HTA for developers of health technologies and their investors (termed 'developers') is different to HTA undertaken later in the technology's lifecycle. Compared to HTA undertaken at market access stage, HTA undertaken to inform developers (termed 'development-focused HTA' or 'DF-HTA') informs a broader range of decisions and has to deal with a greater level of uncertainty, as the precise use of the technology may not yet be known and there is likely to be little evidence specific to the technology. • Although the process of DF-HTA will be familiar to analysts in that it involves the assessment of clinical and economic value, DF-HTA is more iterative in nature and does not have strict methodological guidelines to follow, as is often the case for HTA at market access stage. Analysts can take a more positive stance and put themselves in the shoes of the developer to consider what analysis would be useful to the developer at this stage of development. • The methods would be familiar to those carrying out health technology assessment but need some modification when the work is to inform developers. This is particularly relevant when resources for analysis are constrained, which is often the case when assessing technologies in development, many of which are likely to fail. In practice, this means that methods may be simpler. There is also more emphasis on methods of stakeholder consultation as a result of the lack of clinical evidence. • The framework would benefit from validation through prospective use in further case studies by external groups of analysts. This is particularly important because much HTA work undertaken for commercial developers is not published due to commercial sensitivity. Background and aims The development of health technologies is expensive and high risk, as many technologies in development fail to achieve commercial success. There are many choices to be made during the development process and the decisions made at this time are likely to influence the future success of the technology. It has been suggested that health technology assessment (HTA) undertaken during the development process may help to reduce the risk of failure or to accelerate failure and reduce research waste. The form of HTA used to inform developers about some of the decisions they need to make during the development process has been termed 'Early HTA'. However, the current 'Early HTA' literature includes work which is not intended to directly inform developers (such as HTA accompanying managed access agreements) and much of the HTA that is conducted to inform developers is not published. As a result, there is a lack of clear guidance for the analyst on how to approach HTA to inform developers of medical technologies. This thesis proposes a framework to aid analysts (people undertaking HTA assessments) who are working with developers of medical technologies. The term developers is used throughout to describe the individuals or companies who are developing a medical technology and their investors/funders. Large pharmaceutical and medical device companies tend to have in-house HTA resource (often termed Health Economics and Outcome Research (HEOR) or market access teams). For this reason, the framework is aimed primarily at academic and consultant analysts working with small or medium-sized enterprises (SMEs). The framework comprises three sections: features, process and methods of HTA to inform developers (termed development-focused or DF-HTA). Features means the characteristics of DF-HTA. Process describes the broad activities of DF-HTA. Methods describes the analytical approach to those activities or how the analyst would undertake the activity. The framework was developed alongside five case studies in the assessment of diagnostic technologies which are included to illustrate the framework of features, process and methods. Methods A pearl-growing literature review was undertaken in October 2017 and refreshed in February 2019. Pearl-growing involves searching the citations and references of articles of interest until no further papers are being retrieved. The aim was to retrieve literature which informed an understanding of early health technology assessment and included both methods papers and applied studies. An iterative process was undertaken to develop a framework of DF-HTA including features, process and methods. An initial list of features of DF-HTA was developed then refined and expanded using an iterative process informed by the content of articles identified as being particularly informative and the experience of undertaking the case studies. Frameworks for the process of DF-HTA identified in the literature review were used as the basis for the development of a generic process of DF-HTA. Methods useful for DF-HTA were extracted from review articles. Methods of research and development or other commercial activities were excluded. Terminology was streamlined where similar terms were describing the same method. Five case studies were used to illustrate the framework of DF-HTA. For each of the case studies the features were compared to the list of features and areas of non-conformity identified and discussed. The process of DF-HTA included clinical value assessment in all cases and economic value assessment in four of the five case studies. Methods were selected from the methods identified as useful for DF-HTA. Results A total of 152 early HTA papers were identified of which 88 were judged to be aimed at informing developers. These comprised 56 methods, 61 applied and 35 methods and applied papers in early HTA of which 43 methods, 25 applied and 20 methods and applied were aimed to inform developers. A proposed framework of DF-HTA was developed including the features, a generic process and a range of methods suitable for DF-HTA. Ten features characterising DF-HTA were identified including six which had not been previously identified: audience; timing; decisions informed; available evidence; underlying user objective; decision space; business model; resources for analysis; stance of analysis and burden of proof. The proposed generic process of DF-HTA comprises two core aspects of DF-HTA identified in all the frameworks found in the literature - clinical value assessment and economic value assessment. Clinical value assessment considers what impact the technology might have on clinical practice and ultimately upon health (and wider social) outcomes. Economic value assessment builds on the clinical value assessment to consider the economic impact of changes in healthcare resource use and other economic value drivers such as productivity effects. Eight broad groups of methods useful in DF-HTA were identified from review articles: care pathway analysis; qualitative methods of stakeholder interaction; literature review; multi-criteria decision analysis; discrete choice experiments; expert opinion and elicitation; cost effectiveness analysis and value of information analysis. The framework was illustrated using the case studies. The features of DF-HTA were evident in three case studies of technologies in development but not in two case studies concerning technologies already in clinical use. The process and methods used in the case studies aligned with the generic process of DF-HTA. All the case studies began with a clinical value assessment using decision models to map the existing and potential clinical pathways. For the three DF-HTA case studies parameter estimates came from the literature and expert opinion initially supplemented by evidence from small clinical studies specific to the technology where this was available.

This thesis is a collection of three papers aimed at investigating the macroeconomic effects of oil price shocks on resource-rich economies as well as the appropriate policy responses for ameliorating such effects. The first paper begins by examining the implications of physical capital and oil intensity of domestic production for the response of a small open economy to an oil price shock. Building on the work by Ferrero and Seneca (JMCB 2019), we find that the introduction of physical capital amplifies the responses of output and inflation to oil price shocks whereas the effects are attenuated by the oil intensity in domestic production. Also, our results reveal that the added features are important for the response of monetary policy to an oil price shock. Under our model set up, the optimal monetary policy response requires that the central bank keeps an eye not only on output and inflation, but also the exchange rate. These results highlight the need for cautious interpretation of the quantitative impacts of an oil price shock generated based on New Keynesian models of oil producing economies that abstract from capital. Paper 2 studies the role of oil price shocks in driving business cycle fluctuations of an oil-producing emerging economy with an inefficient fuel subsidy regime. Results from our estimated DSGE model for the Nigerian economy show that output fluctuations are driven mainly by oil and monetary policy shocks in the short run. However, oil shocks play a less prominent role in driving inflation dynamics owing partly to the low pass-through effect of international oil price into domestic prices implied by the fuel subsidy regime. While we find the core inflation-based Taylor rule optimal, we demonstrate that the Central Bank of Nigeria (CBN) faces a dilemma of either stabilising output or inflation in the face of an adverse oil price shock. Simulation results show that an “across-the-board” monetary policy strategy does not exist for dealing with an oil price shock in the resource-rich economy; thus, it is important that the CBN is aware of the observed trade-offs. The last paper investigates monetary-fiscal interactions in a resource-rich emerging economy whose fiscal policy is largely driven by resource-related flows. To achieve this, we analyse Nigeria’s experience over the last two decades by developing and estimating a suitable DSGE model. Our results provide convincing evidence of an active monetary and passive fiscal policy over the full sample. Furthermore, we confirm the presence of revenue substitution; a phenomenon that alters the "automatic stabilisers" role of fiscal policy in the resource-rich economy. The 2008/09 global financial crisis did not significantly alter these findings. However, our results are sensitive to (i) the response of fiscal policy to resource-related flows and (ii) the response of monetary policy to exchange rate.

The mass media represent a powerful societal institution that reflects and shapes the social, cultural and political world. Within health research, media content analysis is an increasingly popular tool for examining how the media represent, and potentially influence, audiences’ understandings of health. This submission comprises eight published papers analysing UK news media representations of health issues and policies, and an explanatory essay. The essay seeks to contextualise the papers within relevant theoretical literatures and demonstrate the papers’ original contributions, both individually and collectively, to knowledge in health communication and policy advocacy. The analytical developments between the submitted papers are contextualised within literatures on the mass media, media research and policymaking, each of which is has been a site of paradigmatic change. The submitted papers demonstrate the application of content analysis to UK newspaper and online news coverage of obesity, single-episodic drinking, alcohol pricing policy, smoke-free policy and e-cigarette regulation. Approaches used include quantitative, qualitative and mixed-methods content analysis, consistent with the epistemological heterogeneity of the field. Each paper is informed by relevant theory, chiefly agenda setting theory and framing theory. While each paper produces its own novel topic-specific insights, the explanatory essay also considers commonalities across topics that lead to transferrable learning for practice in health communication and policy advocacy. The submitted works’ novel contributions to knowledge include: documenting media frames; analysing trends within media frames; documenting stakeholders’ engagement in media debates; highlighting the strategic importance of defining target groups; identifying areas for improvement in media health communication; identifying the need for a social justice approach to public health communication; and identifying the need to engage with values of public health. Specific transferrable learning emerging from synthesis of findings includes: the effectiveness of positioning children as affected groups in negating opposition arguments about individual responsibility; the opportunity to use trends in media coverage to anticipate media framing and policy actor engagement in media debates; and the need for health communication to avoid reproducing harmful stigma, stereotyping and inequality. While content analysis alone cannot provide conclusive prescriptions for media engagement, the submitted works mitigate the inherent restrictions of the method through the use of rigorous, theory-led methods and the triangulation of findings between different topics and analytical approaches. In doing so, the submitted works contribute to a growing international literature by providing health communicators and policy advocates with novel learning that may contribute to practice. The explanatory essay justifies the importance of studying mass media representations of health issues and policies, and demonstrates the contribution of the submitted works to understanding media representations of health issues and informing improved health policy advocacy.

My subject in this thesis is Systemic Risk and the Macroeconomy. The primary focus is on the macroeconomic dimension of Systemic Risk which is the common thread of all four independent essays which compose this dissertation. The first essay studies the macroeconomic relevance of credit supply. How has the transmission of credit supply shocks changed in the past forty years? To study this question, I estimate a time varying structural vector autoregression which allows parameters governing the relationship between credit supply and the macroeconomy to move smoothly over time. The link between credit supply, inflation and leverage is theoretically unclear and ultimately an empirical question. The analysis delivers new results on such relation which may help guide the nascent theoretical literature on the subject. The key empirical findings are: i) Credit supply shocks have had a more muted effect on real activity and inflation in recent decades; ii) Whereas their importance as determinants of leverage in the economy has increased, despite remarkable oscillations. The second paper questions the reliability of the many systemic risk indicators proposed in the literature in signalling downturns of real activity. The link between systemic risk and output growth is hard to study for two reasons. First, the relationship is believed to be nonlinear. Second, systemic risk is unobservable and the myriad of measures proposed in the literature impose the additional challenge of having to deal with model uncertainty. This paper examines the relationship between the quantiles of output growth and systemic risk through the lens of a Bayesian quantile regression. We study, in particular, the relevance of 33 systemic risk indicators to explain lower quantiles of output growth that measure growth fragility. Model uncertainty is tackled by using sparse-modelling techniques that perform both model selection and shrinkage. Only a few systemic risk indicators studied have relevant predictive content for output growth, and instability of predictive relations based on such indicators is the norm. The third chapter aims to advance the measurement of financial conditions. This paper proposes a mixed-frequency factor-augmented vector autoregressive model with time-varying coefficients and stochastic volatility to construct a financial conditions index (FCI). This framework is extended to allow for different unbalanced panel techniques based on probabilistic principal components. In an incomplete data setting, with up to 62\% of data missing, the approach yields a less noisy FCI that tracks the movement of the underlying financial variables more accurately, and delivers better macroeconomic forecasts, on average. A macroeconomic forecasting exercise with the newly constructed FCI may help reconcile opposing views in the literature with regards to the predictive power of financial indicators. The fourth chapter proposes a novel approach to understanding contagion of financial distress in the banking system, which takes into account the spatial nature of the phenomenon. We use a Bayesian spatial autoregressive model that treats the likelihood of default of each bank as endogenous, and dependent on the network formed by all the other banks. Identification is achieved by controlling for bank fundamentals, latent macrofinancial and bank specific shocks that have similar consequences to contagion and act as confounding factors. We find that peer effects account on average for approximately 50 per cent of total distress. Through the lens of a simulations exercise, we study the importance of the structure of financial networks for financial stability shedding light on the empirical adherence of important theoretical prepositions that remain untested.

Robert Burns, the much-loved national (Scottish poet), has been the target of forgers, the most prolific being 'Antique' Smith, who realised the demand for authentic manuscripts which could bring a high price. Antique Smith's forgeries have continued to appear for auction as the real thing long after Smith's time, and suspicion sometimes falls on authentic Burns' documents because of the awareness of the Smith corpus. A chemical method for distinguishing forged from real Burns could have a significant impact on the value of many manuscripts attributed to the poet. We chose to focus on the chemical composition of the inks used in both authentic manuscripts and forged ones. In this study, desorption electrospray ionisation (DESI) and direct infusion mass spectrometry (DIMS) have been applied for the analysis of black inks made using traditional recipes from the 18th and 19th centuries and for historic manuscripts. DESI is an ambient mass spectrometry method that can be used for spatial analysis and imaging of sample surfaces, with very little sample preparation. DESI has been engineered in house, using an existing nano-spray source. DESI directly desorbs sample analytes from a surface under ambient conditions using electrospray ionisation. Optimisation of a DESI method can be very complex as there is a wide array of dependent parameters that can alter the performance which include; nebulising gas flow, solvent flow, voltage and geometrical parameters. Once fully optimised DESI can be very sensitive and non-destructive. The lab-built DESI, based on the Abbassi-Ghadi source, was coupled to Thermo Scientific ExactiveTM OrbitrapTM mass spectrometer. DIMS, which is similar in principle to liquid extraction surface analysis (LESA), operates by picking up sample analytes using a solvent droplet on the surface. Using a methanol water solvent, it has been shown to be minimally destructive. DIMS is performed by placing a pipette tip just above the surface of a document, and pipetting up and down three times. Direct infusion was then carried out, using the solvent containing the sample analytes with an Advion TriVersa nanomate set up for chip-based infusion coupled to a Thermo Scientific Orbitrap FusionTM TribridTM mass spectrometer. The sampling process of DIMS can be performed out of the laboratory setting, which eliminates the need for transportation of the historic documents. DESI imaging has been successfully performed on rhodamine 6G, and for the analysis iron gall and ivory black inks. The word 'Polyomics' written in rhodamine 6G on a glass slide, was imaged using low spatial resolution of 1.25 mm steps per line as a 'proof of concept' experiment. An array of letters was written onto handmade cotton paper where ivory black ink was successfully imaged in positive ionisation mode with a unique peak at 375.21 m/z. In negative ionisation mode iron gall inks could be spatially identified using a unique peak at 220.15 m/z. It was concluded that further optimisation of the DESI method would be required however, before being suitable for the analysis of historic documents. The DESI source was investigated for the analysis of cow's milk and amino acids. In DESI there are two main groups of analytes, electrospray ionisation (ESI) and atmospheric-pressure chemical ionisation (APCI), which require different DESI parameters for successful ionisation. The analysis of cow's milk produced a complex lipid spectrum. Lipids belong to the ESI group of analytes, in the experiment groups of glycerolipids were identified. This indicates that the lab-built DESI source is capable of ionising this group of analytes. High mass spectral resolution mass spectrometry was used, providing high mass accuracy, which eliminates the requirement for chromatographic separation, although tandem mass spectrometry would be required for further identification of the lipids. Amino acids however, are within the APCI group of analytes, and have been shown to be successfully spatially detected using DESI. Ink components will be within the same group of analytes as amino acids, which demonstrates suitability for this group of analytes. DIMS was used for the first time to analyse the inks and paper used by Burns and Smith. It was shown using DIMS that iron gall inks and ivory black inks can be distinguished successfully, therefore, 9 manuscripts known to be written by A. Smith and 3 manuscripts written by R. Burns were analysed. A unique chemical fingerprint was created for each of these manuscripts. It was found that there were 94 discriminatory peaks (Q < 0.05) distinguishing Burns and Smith manuscripts, of which 42 of these were not detected in any of the solvent peaks. A support vector machine classifier was produced with a 0.76 AUC value which distinguishes these authors works. Eight significant peaks were carefully selected for further analysis with annotations where available. DIMS could have a broad application, aiding collectors of historic literary works and auction houses with the authentication of spurious documents. It would be necessary to create a library using DIMS, sampling a wide range of manuscripts from different time periods from around the world, incorporating different historic figures literary works. A number of chemical classifiers could be produced and used to identify the origin and time period, and therefore authenticity, of spurious manuscripts.

This thesis seeks to examine contemporary factors that prevent an orderly resolution to a sovereign debt crisis. It comprises of five chapters. The first chapter introduces the research and highlights its main contributions. The second chapter narrates the background and motivation for the study. The third chapter studies a related paper on holdouts in sovereign debt restructuring and finds that, under a discrete time version with two creditors, asymmetric pure strategy Nash equilibria exists. This result, overlooked by the original paper, implies immediate agreement as the time between successive periods tends to zero. The fourth chapter investigates the impact of heterogeneous beliefs on delays in sovereign debt restructuring and finds that parties inefficiently delay settlement when their combined beliefs of court-outcomes are sufficiently heterogeneous. The chapter also explores other model expositions and establishes delay conditions. The fifth chapter studies the implied duty on the debtor to act in good faith in sovereign debt restructuring and is divided into two parts. The first part theoretically examines the efficiency and distributional impacts from enforcing a good faith duty on the debtor when bargaining with heterogeneous creditors. Here, good faith is defined as the non-violation of the court interpretation of the pari passu clause. The second part identifies judicial attempts made to enforce the good faith debtor duty to negotiate and proposes a doctrinal threshold that restricts judicial intervention to situations in which there is clear evidence of a failure, on the part of the debtor, to negotiate in good faith.

Clan MacKenzie was a dominant force in Ross-shire throughout the seventeenth century and in the early eighteenth century. Its chiefly line was the MacKenzies of Kintail/Seaforth, who at times were the earls of Seaforth and Jacobite marquesses of Seaforth, sheriffs of Ross-shire, provosts of Fortrose, Scottish Privy Councillors and Jacobite secretary of state for Scotland. However, the noble house of Seaforth remains under-analysed in scholarship for the period after 1639. Instead, scholarship tends to approach the Scottish Highlands and Highland nobility during the temporal span of this thesis (1651-1719) from an Edinburgh- and London-centric perspective and, therefore, through nobles and clans who engaged more regularly with the Scottish and British central authorities, such as the house of Argyll, consecutively chiefs of Clan Campbell. This has led to skewed understanding of Highland nobility and clanship during this period. Taking inspiration from successful noble- and Highland-centred approaches to historical research, this thesis describes and analyses the change in the strength of the house of Seaforth through focused studies on the political careers of Kenneth Mòr MacKenzie, third earl of Seaforth (1651-78), Kenneth Òg MacKenzie, fourth earl of Seaforth (1678-1701), and William Dubh MacKenzie, fifth earl of Seaforth (1701-19). To accomplish this, this thesis utilises source material irrespective of its genre or the language in which it was written, painting a multi-layered picture. This thesis uses a mixture of family papers and correspondence, governmental records, Gaelic poetry and genealogical histories to assess how the nature of Highland noble power changed from the perspective of the chief, revealing his apparent strategy. More broadly, this thesis provides a local, Seaforth-centred perspective of the years 1651-1719 in order to challenge and complement long-held historiographical beliefs on national phenomena, such as on minority and absentee lordship, Highland nobles and their gentry, clans and royalism and Jacobitism, clans and religion, and clans and politics.

Understanding the impact of Corporate Social Responsibility (CSR) on firm performance as it relates to industries reliant on technological innovation is a complex and perpetually evolving challenge. To thoroughly investigate this topic, this dissertation will adopt an economics-based structure to address three primary hypotheses. This structure allows for each hypothesis to essentially be a standalone empirical paper, unified by an overall analysis of the nature of impact that ESG has on firm performance. The first hypothesis explores the evolution of CSR to the modern quantified iteration of ESG has led to the institutionalization and standardization of the CSR concept. The second hypothesis fills gaps in existing literature testing the relationship between firm performance and ESG by finding that the relationship is significantly positive in long-term, strategic metrics (ROA and ROIC) and that there is no correlation in short-term metrics (ROE and ROS). Finally, the third hypothesis states that if a firm has a long-term strategic ESG plan, as proxied by the publication of CSR reports, then it is more resilience to damage from controversies. This is supported by the finding that pro-ESG firms consistently fared better than their counterparts in both financial and ESG performance, even in the event of a controversy. However, firms with consistent reporting are also held to a higher standard than their nonreporting peers, suggesting a higher risk and higher reward dynamic. These findings support the theory of good management, in that long-term strategic planning is both immediately economically beneficial and serves as a means of risk management and social impact mitigation. Overall, this contributes to the literature by fillings gaps in the nature of impact that ESG has on firm performance, particularly from a management perspective.

This thesis provides an in-depth discussion of housing markets and their effects on the volatility of aggregate economy. This thesis consists of three major theoretical models and one empirical model. Chapter one gives an introduction to the housing markets and what the literature suggests about their effects on the wealth of households, as well as the contribution and structure of the thesis are discussed. Chapter two examines the role of collateral constraints in a baseline model with no Buy to Let (BTL) sector in the economy. Using a core framework of Dynamic Stochastic General Equilibrium (DSGE) models, I found that when houses act as collateral, change in house prices have a substantial effect on the consumption of agents who are collaterally constrained. In particular, Borrowers are better off when the house prices are subjected to an increase, compared to that of agents who are not collaterally constrained. Furthermore, when amount of lending is based on income, I found that labour dynamics play a huge role and Borrowers are subjected to a substitution effect with a positive technology shock in housing market and this leads to an increase in labour and net income of Borrowers and in turn an increase in the their housing is observed. In light of the Bank of England paper by Baptista et al. (2016) and then consultation by the Financial Policy Committee (FPC) on the risks of BTL markets on the economy, chapter three examines the role of BTL markets on the volatility of house prices using a DSGE framework with Dixit Stiglitz Lite Utility. As the policy is expected to operate at business cycle frequency, I built a DSGE model rather than an OLG model. The results from the model indicate that by altering the size of BTL markets using downpayment ratio as a macro prudential policy has a very little effect on the volatility of house prices as opposed to the agent based model Baptista et al(2016). Such results indicate that there is a chance for some serious supply constraints in the economy especially in the urban areas. However, changes in size of BTL markets do have a substantial effect on the volatility of an aggregate economy. This leads us to chapter four, which investigates the effects of a rich set of shocks including news shocks on my model economy with agents subjected to CES utility. I use this framework to analyze which policy out of the Macro prudential of Downpayment ratio and Monetary policy is better to curb the volatility of the aggregate economy. The results indicate that labour markets play a pivotal role in most of the dynamics and the volatility stemmed from the Monetary policy shock is substantially high on housing market compared to that of the consumption goods market. I also found that Monetary policy is the only effective policy which affects the Hand to Mouth agents optimal choices. However, Macro prudential policy is more effective in both the Borrowers and Savers volatilities of choice variables. With a News shock in Monetary policy, I tend to observe that the economy volatility is only affected by the Monetary policy with no affect from Macro Prudential policy. Finally in chapter five, I take my baseline models augmented with habit formation: one without housing and the other one with housing, to data. Using the 1980 to 2020 quarterly data of U.S and employing the Bayesian Estimation techniques, I have estimated some key parameters and compared the estimated parameters between the two baseline models. Results show that most of the estimates are in line with the literature. Inclusion of housing has substantially increased the effect of the monetary policy and it's persistence in the economy. Due to the inclusion of collateral constraint, agents are subjected a better wealth effects and this leads to them reacting less to the change in wages. Habits have slightly increased with the inclusion of Borrowers in the economy as they are constrained and to account for the aggregate consumption levels, Borrowers tend to form higher internal habits in consumption.