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Alpha-1 antitrypsin deficiency (AATD) is a major risk factor for chronic obstructive pulmonary disease (COPD) and specifically development of pulmonary emphysema at an accelerated rate. The strong emphysema phenotype associated with AATD related lung disease would suggest that interventions which reduce emphysema decline are logical approaches. Such therapies are much needed with a paucity of new treatments in the last three decades. This thesis explores interventions that target two models of emphysema progression; 1) accelerated lung destruction from pulmonary exacerbations and 2) overall basal elastin degradation rate. As with usual COPD, individuals with AATD often suffer with periodic worsening of symptoms known as exacerbations. Exacerbations contribute to reduced quality of life (QOL) for individual patients and are a significant financial and resource burden. They also accelerate emphysema decline. Most exacerbations present with a combination of breathlessness, increased sputum production and increased sputum purulence but it is not understood which exacerbation phenotypes lead to lung damage. Symptoms alone are unlikely to make this distinction. The discovery of a specific biomarker that detects the start and recovery from an exacerbation, in combination with symptoms, would not only guide management options but identify pathophysiological pathways with potential discovery of novel drug targets. The first intervention involves the use of both detailed symptom monitoring and point of care (POC) biomarker tracking for the early detection and treatment of exacerbations. These interventions were assessed via the 'Elastin degradation in exacerbations of AATD related lung disease' study, an 18-month prospective cohort of 55 AATD patients with frequent exacerbations. The hypothesis was that prompt and appropriate treatment of exacerbations could limit their destructive effects and therefore slow emphysema progression. Since an enhanced monitoring approach is fairly novel, the main aim of this study was to assess feasibility and efficacy of an electronic symptom diary (eDiary) and POC urine lateral flow immune assay alongside identification of a suitable urinary biomarker. Promising results would then prompt assessment of whether emphysema progression is improved with such interventions. Results showed that the use of an eDiary was feasible and was able to predict exacerbations, though not accurately enough to be used alone. The addition of urinary biomarkers was unable to improve the predictive algorithm. There were mean changes in CRP and TIMP1 across the time course of an exacerbation. The pilot data from the urine device has pioneered alterations to its design to improve its accuracy and reliability. The second model of emphysema progression, basal elastin degradation rate, already has an established therapy. Alpha-1 antitrypsin (AAT) augmentation therapy has been shown to slow the rate of decline in CT lung density and is currently the only approved disease modifying therapy for AATD patients. The effect of augmentation therapy on more conventional outcomes such as mortality and QOL have not yet been established which has delayed approval of augmentation therapy in the UK. This thesis explored the efficacy of AAT augmentation therapy via a large prospective study comparing two separate cohorts of AATD patients; one receiving AAT augmentation therapy and one standard COPD care alone. This was designed to investigate conventional outcomes that have not been addressed through randomised controlled trials. Results showed that the mortality benefit of AAT augmentation therapy remains uncertain, though there appears to be a reduction in rate of decline in QOL in the augmentation group compared to control. The cost effectiveness of augmentation therapy is also discussed.

The research captured in this thesis has led to the development of a range of models, tools and processes for government and industry that provide a forwardlooking approach to the measurement of impact on infrastructure projects. This approach enables measurement of United Nations' Sustainable Development Goals (UN SDG) at the project level to ensure investments are made equitably across economic, environment and social objectives. Application of the results from this research are already being actively used by the Environment Agency to manage impact assessment across its £5.2Bn portfolio of projects and by the Thames Tideway Project (£4.9Bn). Background. Achievement of the United Nations' Sustainable Development Goals (SDGs) by the year 2030 is of paramount importance and the construction industry has a major role in achieving a measurable impact against the SDG targets. However, linking of 'local' infrastructure project success to 'global' SDG targets is problematic because the targets were designed at the national level and not at the project or programme level (Mansell, et al., 2020a). Furthermore, while the so called 'triple bottom line' (i.e. economy, environment and society) approach to understanding sustainability remains important, there is a need to understand how this can be related to the full project lifecycle as well as a need for improved project governance. This is consistent with the findings of a key UN investigation's Fourth Report (Global Task Force, 2020) which calls for localization of SDGs as well as the need for cooperative governance to establish shared priorities. Research description. The research was based on two main stages. The first stage, informed by a systematic literature review, comprised a mixed method that involved a survey of 325 engineers to derive quantitative data (Mansell et al., 2020b) along with interviews with 40 CEOs and corporate Heads of Sustainability to capture qualitative data (Mansell et al., 2020c). The second stage involved the development of a prototype that was tested through two further exploratory investigations at two levels: (1) Test 1: is there a Golden Thread from global SDGs, through the organisational level, down to project level SDG impact measurement?; (2) Test 2: does the prototype model, the Impact Value Chain, have practical coherence when PhD: Measuring Infrastructure Projects' SDG Impact (MISI) v assessed in a brief case study of a Water Utility Company (Anglian Water) (Mansell et al., 2020d). Subsequently, and not part of this thesis, the research led to a collaborative partnership to test the prototype model and its approach across the Environment Agency's full portfolio of projects and also, the megaproject of the Thames Tideway Tunnel. Findings. The survey of 325 engineers (Mansell et al., 2020b) indicated four primary shortfalls for measuring SDGs on infrastructure projects, namely leadership, tools and methods, engineers' business skills in measuring SDG impact, and how project success is too narrowly defined as outputs (such as time, cost and scope) and not outcomes (longer-term local impacts and stakeholder value). Moreover, the interviews with 40 senior executives (Mansell et al., 2020c) from the UK identified that SDG measurement practices are currently 'more talk less walk' and indicated a number of contextual and mechanistic opportunities to increase the outcome success. Therefore, using empirical evidence the researcher identified a 'golden thread' between best practice sustainability-reporting frameworks at the 'local' project level and those at the organisational and supra-national-levels (Mansell et al., 2020a). In doing so, the research identified that there is sufficient linkage to embed SDG impact targets into the design stage of an infrastructure project. Furthermore, the innovative process model, called the 'Infrastructure SDG Impact-Value Chain' (IVC) to link project delivery with strategic SDG impacts, builds on the concept of creating shared value and creates a practical mechanism to turn theory into meaningful impact in project selection and delivery. The utility of the IVC process model was initially investigated as part of the case study investigation of Anglian Water (Mansell et al., 2020d) and its application has been further demonstrated in the MISI Project (not included in this thesis). Research Impact. The research produced twelve peer-reviewed papers including being published in seven internationally recognised academic journals, such as: Sustainability (2 articles), Administrative Sciences, and the Proceedings of the Institution of Civil Engineers-Engineering Sustainability. The MISI research outputs have been taken forward by the government and industry partners, specifically the Environment Agency and Thames Tideway Project, working together to establish this new approach for measuring sustainability on infrastructure projects.

This thesis describes qualitative research into the experience of executive leaders and software engineers engaged in innovation in British small- and medium-sized software enterprises (SMSE). It asks, "How are executive leaders of British SMSE perceived to influence the innovative work behaviour of software engineers?". Executive leaders, software engineers, and private equity (PE) investors were interviewed, and the data transcribed and coded using constructivist grounded theory methodology (CGTM) (Charmaz 2014). Coding revealed new insights into innovation leadership in SMSE. Theory suggests innovation is important to firm survival and success (Pisano 2019). Leader support for creativity and innovation in software firms is considered strategic (Florida and Goodnight 2005). However, executive leaders in this study were concerned with cash generation, primarily focusing on customers and funders. Once firms established product market fit, innovation became incremental, focused on features, functions and processes. Leaders were transactional (Bass 1985) and instrumental (Antonakis and House 2014) in their interaction with engineers and did not try to influence creative climate (Amabile 1996; Ekvall 1996), pursuing exploitative incremental innovation and rarely considering exploratory innovation (Tushman and O'Reilly 1996). Software engineers had little interest in commercial matters, but favoured innovation, particularly if it allowed them to use new tools, techniques, and languages. They embraced technical change but were less comfortable with cultural change. They did not establish close relationships with their leaders and saw them as being responsible for providing resources to enable objectives to be achieved. PE investors aspired to invest in firms that had established product market fit and were focused on growth and margin improvement. They rarely supported innovation requiring additional funding or not focused on improving short-term competitive advantage or margin. They preferred working with executives focused on delivering the original investment thesis and so tolerated incremental innovation but were less supportive of explorative innovation.

To improve democratic legitimacy, successful resolution of public policy challenges has to emerge from highly pressurised political predicaments. Increasing civic functionality requires integrative Civil Service practice, building trust in adaptive oversight. With the task of effective governance stretching out-of-reach in straining institutional arrangements, a proposition is developed for an “Attainable Governance” reset to revitalise democracy. Motivated by the need for progress that is sensitive to the reality and risks of the present and embodying requirements to hold open unforeseen possibilities for future action, the groundwork is laid for a new “decision architecture” that improves policy-framing and decision-making. With a mission to compose a conceptual framework for “facing the future” in the United Kingdom, I make the case for refreshing democratic arrangements, including a proposed structural intervention to the policy-making system with a correlative cultural step-change in leadership. Laying out a novel framework, the analysis draws widely on strands of thinking in social theory and political philosophy, public administration and policy-making, systems thinking and design, planning and strategic management, anticipation and futures, economics, and sociology. Taking an “integral” methodological orientation, in three parts I: (1) diagnose the converging Predicament, (2) develop a conceptual Proposition, and 3) sketch-out an approach to leadership that facilitates operational adaption in Procedures for applied practice. Positing that we have to deal with systems-of-problems (“messes”) and system-of-systems (“systemic messes”) with an analytic primacy on expanding temporal considerations to factor in more anticipative insights, I take a Complex Adaptive Systems-informed stance. The need for a “Decisive Reset” to refresh democracy, featuring phased systemic reordering and tactical modularity to produce better public decision-making that is responsive and agile in the short-run, while actively gauging medium-term realities and future-proofing for long-run uncertainties, results in a new decision architecture and methodology.

My thesis explores the way in which the Italian language and literary culture contributed to John Milton’s early development as a poet (over the period up to 1639 and the composition of Epitaphium Damonis). I begin by investigating the nature of the cultural relationship between England and Italy in the late medieval and early modern periods. I then examine how Milton’s own engagement with the Italian language and its literature evolved in the context of his family background, his personal contacts with the London Italian community and modern language teaching in the early seventeenth century as he grew to become a ‘multilingual’ poet. My study then turns to his first published collection of verse, Poems 1645. Here, I reconsider the Italian elements in Milton’s early poetry, beginning with the six poems he wrote in Italian, identifying their place and significance in the overall structure of the volume, and their status and place within the Italian Petrarchan verse tradition. After considering the significance of the Italian titles of L’Allegro and Il Penseroso, I assess the impact of Italian verse forms (and particularly the canzone) upon Milton’s early poetry in English and the question of the nature of the relationship between Milton’s Mask presented at Ludlow Castle and Tasso’s ‘favola boschereccia’, Aminta. Finally, I consider the place in Milton’s career of his journey to Italy in 1938-9 and its importance to him as a personal ‘conquest’ of Italy. I suggest that, far from setting him upon the path toward poetic glory, as is often claimed, his return England marked the beginning of a lengthy hiatus in his poetic career. My argument is that Milton was much more Italianate, by background, accident of birth and personal bent, than has usually been recognised and that an appreciation of how this Italian aspect of his cultural identity contributed to his poetic development is central to an understanding of his poetry.

This thesis draws on over eighteen months of multi-sited fieldwork carried out in London and Dhaka, among geologists, lawyers, fund managers, engineers, and private sector development consultants intent on securing profitable extractive opportunities in new ‘frontier' markets, and among public intellectuals and politicians in Dhaka who oppose the development of Bangladesh's energy resources by foreign corporations. The thesis contributes to a recently revitalized anthropological political economy and engages critically with the actor–network theory-inspired ‘social studies of finance'. By tracing ethnographically the production of extractive industry capitalism, I show that capital is not merely free–flowing or reproduced by its own inevitable logic. Rather, the movement and accumulation of capital is facilitated by distinct forms of knowledge production, such as political risk analysis and the emergent field of Corporate Diplomacy, and by historically constituted legal norms, most notably those of investor–state arbitration. Equally, I show that the calculative capacities exercised by financial analysts and fund managers have material consequences far beyond those normally considered by scholars in the social studies of finance, who tend to confine their analyses to the ‘bounded fieldsites' provided by bank dealing rooms or stock exchange trading floors. Methodologically, this thesis defends the notion that ethnographically tracing the generation of extractive industry capitalism demands a rejection of the recent ‘post–critical' turn in the ethnography of experts and elite groups. Ultimately, I argue that what allows extractive industry capitalism to be generated is the subordination of the sovereignty of ‘frontier' states to the sovereignty of transnational extractive corporations. This subordination is supported by the norms of international arbitration, and is the source of the perceived ‘investment climate' stability that ultimately allows extractive industry capitalists to attract speculative investment for resource exploration in new ‘frontiers'.

In this thesis the research presented relates to topological solitons in (2+1) and (3+1)-dimensional Skyrme theories. Solutions in these theories have topologically invariant quantities which results in stable solutions which are topologically distinct from a vacuum. In Chapter 2 we discuss the broken baby Skyrme model, a theory which breaks symmetry to the dihedral group D_N. It has been shown that the unit soliton solution of the theory is formed of N distinct peaks, called partons. The multi-soliton solutions have already been numerically simulated for N = 3 and were found to be related to polyiamonds. We extend this for higher values of N and demonstrate that a polyform structure continues. We discuss our numerical simulations studying the dynamics of this model and show that the time dependent behaviour of solutions in the model can be understood by considering the interactions of individual pairs of partons. Results of these dynamics are then compared with those of the standard baby Skyrme model. Recently it has been demonstrated that Skyrmions of a fixed size are able to exist in theories without a Skyrme term so long as the Skyrmion is located on a domain wall. In Chapter 3 we present a (2+1)-dimensional O(3) sigma model, with a potential term of a particular form, in which such Skyrmions exist. We numerically compute domain wall Skyrmions of this type. We also investigate Skyrmion dynamics so that we can study Skyrmion stability and the scattering of multi-Skyrmions. We consider scattering events in which Skyrmions remain on the same domain wall and find they are effectively one-dimensional. At low speeds these scatterings are well-approximated by kinks in the integrable sine-Gordon model. We also present more exotic fully two-dimensional scatterings in which Skyrmions initially on different domain walls emerge on the same domain wall. The Skyrme-Faddeev model is a (3+1)-dimensional non-linear field theory that has topological soliton solutions, called hopfions. Solutions of this theory are unusual in that that they are string-like and take the form of knots and links. Solutions found to date take the form of torus knots and links of these. In Chapter 4 we show results which address the question of whether any non-torus knot hopfions exist. We present a construction of fields which are knotted in the form of cable knots to which an energy minimisation scheme can be applied. We find static hopfions of the theory which do not have the form of torus knots, but instead take the form of cable and hyperbolic knots. In Chapter 5 we consider an approximation to the Skyrme-Faddeev model in which the soliton is modelled by elastic rods. We use this as a mechanism to study examples of particular knots to attempt to gain an understanding of why such knots have not been found in the Skyrme-Faddeev model. The aim of this study is to focus the search for appropriate rational maps which can then be applied in the Skyrme-Faddeev model. The material presented in this thesis relates to two published papers and corresponding to Chapters 2 and 3 respectively, which were done as part of a collaboration. In this thesis my own results are presented. Chapter 4 concerns material which relates to the preprint which is all my own work. Chapter 5 discusses my own ongoing work.

The fascinating field of molecular capsules has recently begun to see the creation of structures that, medicated by the encapsulation of guest molecules within their central cavity, are able to change the properties or reactivity of the substrate. The current capsule designs are however, prone to exchange of either part or whole ligands. This exchange or the capsule's subsequent disassembly can lead to loss of the cavity or modification of their external properties, and is a barrier to their more widespread application, a problem this work seeks to address by creating more a robust capsule structure. This thesis presents the design, synthesis and properties displayed by three novel capsules. All the species presented share a similar supramolecular tetrahedral structure, but their properties deviate significantly, showing either switchable behaviour, spin-crossover or a novel synthetic route to a kinetically inert structure. Improvements in the design have led to a final capsule that is water-soluble, robust, non-toxic and has been shown to encapsulate a range of guests. Chapter 1 includes an overview of the types of capsule constructed in literature and their possible application. The fundamental properties of these capsules are identified, with emphasis given to a discussion of mechanisms underlying their encapsulation phenomena. Chapter 2 describes efforts to construct a tetrahedral capsule based on iron(II) and an oxime ligand. While the use of an oxime motif achieved the aim of preventing exchange of the external groups, the capsule also displayed the surprising property of possessing a solvent responsive assembly-disassembly process. This potentially provides a basis for 'on-demand' encapsulation by being able to choose when to have hydrophobic cavity available for guests. Chapter 3 details the synthesis of a tetrahedral capsule containing iron (II) coordinated by a pyridyl-triazole bonding motif. the spin-crossover properties of the complex were initially demonstrated in the solid state, however, when in solution the capsule displayed the unusual ability of spin-crossover mediated structural rearrangement. Chapter 4 demonstrates the synthesis of a robust capsule. The synthetic route shown alleviates the problems surrounding the construction of inert species in a self-assembly process. Based around a cobalt (III) cation, the stability of the capsule to carious conditions is examined and its host-guest chemistry is explored, revealing some insights into the encapsulation behaviour of this structure.

The body of this thesis looks at two large observational programmes: The VLT-FLAMES Survey of Massive Stars (VFSMS) and The VLT-FLAMES Tarantula Survey. The VFSMS aimed to advance the current understanding of massive star evolution by pressing the issue of rotational mixing for a sample of over 700 early type stars in the Galaxy and Magellanic Clouds. The YFTS is an extension of the VFSMS to study, in detail , the comparison of binary and single massive stars. A detailed investigation into several different massive star populations is given, from both the VFSMS and the VFTS. The work of the VFSMS is focused on a sample of 64 Be-type stars within the Magellanic Clouds . Atmospheric parameters and photospheric abundances have been used to show the Be-type star sample is inconsistent with stars rotating close to critical velocity. The VFTS investigates the number of B-type binary systems within the 30 Doradus region of the LMC, by using a cross correlations analysis technique. A binary fraction of 29% is determined from over 500 B-type stars, further refined to a true binary fraction of 66% by modelling the sample incompleteness. From the binary search, investigations are presented into three high radial velocity variable stellar objects. Firstly a study highlights the B[e] phenomenon through the analysis of the supergiant B[e ]-like binary, VFTS698. Secondly a detailed analysis of two Tare blue supergiant binary systems, VFTS450 and VFTS652 is undertaken. Finally consideration is given to the remaining B-type star samples of the VFTS that require further investigation, viz. the projected rotational velocity distribution of binaries, and the potential short-period binary systems.

Straw price increases due to biofuel demand have created a perceived need within the agricultural industry to investigate and develop alternative bedding materials for housing ruminant livestock. This thesis addresses the suitability of woodchip, as such an alternative, indoor bedding material for livestock, focusing particularly on management of the soiled bedding, its nutrient composition, its use as an agronomic resource and its economic viability within the Welsh farming sector. In all studies, straw was used as the benchmark to which the woodchip treatments were compared. Many studies have investigated the use of woodchip in out-winter pads (OWP), but the material’s indoor performance and in particular, its potential for re-use, is not well documented. Two independent housing trials, both including sheep and cattle, were conducted. The first trial (ADAS) assessed the effect of different initial woodchip moisture contents on the performance of the bedding material and its subsequent composting. The second trial (IGER) evaluated the effects of hay and silage diets on woodchip’s bedding and composting performance. The ADAS trial showed that woodchip’s absorbency capacity and physical shape were critical in determining its bedding and composting success. In comparison to differences determined by bedding materials and livestock characteristics, the IGER trial suggested that dietary inputs had little influence on the woodchip’s bedding and composting performance. Overall, the results indicate that composting of spent woodchip bedding was less effective than that of straw bedding, due to the lack of available N which limited microbial activity. The limited breakdown of the woodchips during composting, however, does potentially allow the re-use of the bedding materials for further housing cycles. Barley sown growth trials, amended with composted bedding materials showed that woodchip composts yielded reduced biomass in comparison to conventional NPK based fertilisers and straw bedding compost. When the coarse woody fraction of the compost was removed (>8 mm in diameter), leaving just the fine (< 8mm) nutrient-enriched fraction, plant growth performance was slightly enhanced at application rates equivalent to 100 t ha-1. Estimates of N loss from woodchip treatments were high during housing, but limited during composting due to a generic lack of available nutrients, compared to straw. Using economic modelling, a cost/benefit analysis of woodchip bedding versus straw showed that woodchip is more cost efficient than straw on the condition it is re-used. In summary, the thesis concludes that woodchip is a potentially viable alternative to straw bedding for Welsh farmers, on condition of specific management practices. Future work is required to identify and mitigate N losses during the woodchip bedding phase.

Portable gas containers are utilised by a wide range of end users to enable the transport of gases such as air and oxygen. Such vessels are well established in the medical and self-contained breathing apparatus (SCBA) markets. The increasing use of CNG and other alternative fuels in automotive applications is a driving growth of high-pressure gas containers in the automotive market. The research presented here concerns the manufacture of pressure vessels through alternative routes, with a focus on braiding, in order to reduce the costs of manufacture. Several mandrel winding methods through braiding were developed in order to wrap aluminium gas cylinder liners. The geometry of the domes presented several challenges to preforming. In particular, achieving high, uniform reinforcement angles in the hoop lamina was not possible by over-braiding the dome sections of the vessel. The vessels were designed and produced to pass pressurisation tests and cyclic loading tests according to the EN12245 test standard. A proof of concept for the braided composite pressure vessels was carried out through a scheme of design and testing. The testing scheme employed braided hoop and helical winding and resin infusion processes to produce braided vessels with performance that was equal to the filament wound vessels. The process identified that the braided reinforcement gave similar strengths to that of the wound reinforcement despite the presence of crimp. The fatigue performance of the braided vessels was found to exceed the performance of the filament wound vessels. Finite Element (FE) models of mesoscale braided tow geometries were produced in order to examine the modulus and stress concentrations in the undulating tows. Good agreement between the experimental modulus and FE modulus was found for the 80˚ braided unit cell model.

The current thesis aimed to explore the associations between hazardous drinking, automatic processing of alcohol-related cues and behavioural impulsivity. In addition to assessing the impact of these processes on hazardous drinking in isolation, the specific prediction of dual process models of addiction, that the association between automatic cognitive processes and hazardous drinking would be moderated by behavioural impulsivity, was also tested. These general research questions were investigated cross sectionally in young adult student populations (chapter 3), / adolescents (chapter 4), and older adults (chapter 5). The aim of the study described in chapter 6 was to investigate the effect of a priming dose of alcohol on these processes and their association with alcohol-seeking behaviour. Finally, chapter 7 was an investigation into the mediators and moderators of the effects of ego depletion on drinking behaviour from the perspective of dual process models of addiction. Automatic processing of alcohol-related cues predicted drinking behaviour in all cross sectional studies, although the specific aspects of automatic processes that predicted drinking behaviour differed. The effects of the alcohol prime and anticipated effects of alcohol on different measures of cognitive bias were inconsistent, and automatic cognitive processes only predicted ad-lib drinking in non-intoxicated individuals. Impulsivity only had a direct association with drinking within the sample of older adults, and neither the alcohol prime or ego depletion manipulation increased either measure of behavioural impulsivity. There was evidence that the alcohol priming effect was the result of general impairments in executive cognitive functioning. In the cross sectional studies support for dual process models of addiction was only found in the adolescent sample, in which impulsive decision making moderated the association between attentional bias and problem drinking in adolescents. There was evidence that increases in automatic approach responses towards alcohol-related cues following an alcohol prime were the result of impairments in executive cognitive function. Although ego depletion resulted in increased alcohol consumption this was not due to increased behavioural control by automatic cognitive processes. The results from the current thesis offer considerable support for incentive- motivational models of addiction, arid-highlight the importance of the roles of specific aspects of automatic cognitive processing in different samples. As behavioural impulsivity was only associated with hazardous drinking in older adults this suggests that cumulative experience with alcohol is necessary before these processes impact behaviour. Although support for dual process models of addiction was only found in adolescents, previous research would suggest that the predictions of these models are most likely to be found in such samples.

The existence of a significant non-baryonic component to the Universe is widely accepted, with worldwide efforts underway trying to detect this so-called dark matter. The ZEPLIN-III detector utilises liquid xenon (Xe) as a target medium in the search for the expected rare interactions of Weakly Interacting Massive Particles, or WIMPs, with ordinary baryonic matter. The neutralino, arising in supersymmetric extensions to the standard model of particle physics, provides a particularly well-motivated candidate. The ZEPLIN-III experiment, operating in two-phase (liquid/gas) mode, measures both the scintillation and ionisation signatures produced during an interaction. The first science run (FSR) of ZEPLIN-III was performed during three months in 2008. The run culminated in a published result which excluded a WIMP-nucleon interaction cross-section above 8:1 x 10-8 pb for a 60 GeVc-2 WIMP at the 90% confidence level. ZEPLIN-III then entered an upgrade period where the photomultiplier tube (PMT) array, previously the dominant source of background, was replaced with new, ultra-low background, PMTs. The radio-contamination of components used to make these PMTs has been thoroughly studied and their impact on the background rates in ZEPLIN-III characterised. Additionally, a new 1.5 tonne plastic scintillator veto detector was constructed, increasing the ability to reject WIMPlike signals caused by neutron induced nuclear recoil events and improving the γ-ray discrimination capability of ZEPLIN-III. The second science run (SSR) of ZEPLIN-III began in June 2010 and continued for 6 months, with a projected upper limit for the interaction cross-section of 1:52 x 10-8 pb for a 55 GeVc-2 WIMP at the 90% confidence level.

Accounts of contemporary mental health policy and practice are contested and diverse. Yet they tend to share an implicit ontological commitment to a logic or 'register' of specialism. That is, they fundamentally assume the existence of a range of professional and disciplinary activities designated by 'mental health work' may be unproblematically divided off from other areas of social activity and relations. In this thesis I contrast the register of specialism to a register of suggestion. Firstly, this notion evokes comparatively neglected aspects of the histories that condition present-day practice. More importantly, making primary recourse throughout the thesis to the work of A.N. Whitehead as inspiration and lure, I argue that suggestion offers a fertile conceptual device that problematises subject-predicate modes of thought underpinning 'specialist' accounts. Moreover my approach opens up inter-connections and contingencies between mental health work and the affective as well as socio-technical dimensions of everyday life. The thesis draws on empirical material gathered during a six-month ethnographic study of a multidisciplinary Community Mental Health Team in London. Using the contrast between suggestion and specialism as a key conceptual device I focus on team members' experience of risk and of the tension between crisis and routine and on the ways in which they participate in the constant reconfiguration of order within their day-to-day work. I will argue that regarding workers as constantly and fundamentally 'open to suggestion' not only allows otherwise neglected and creative aspects of practice to emerge to the fore. It also raises important methodological and epistemological questions concerning processes of social change and (insofar as adoption of the register of suggestion bears implications for the notion of an ethnographic sensibility) for the enterprise of social research itself. Thus the thesis reaches beyond the remit of mental health work as conventionally interpreted. It resonates with established and contemporary controversies within social theory around methodological challenges and limitations and within the sociology of health and medicine around the nature of therapeutic change. It is posited simultaneously as directly relevant to practitioners and policy-makers working in the mental health field and as an intervention in these ongoing social-theoretical debates.

The challenging cultural context of the United States presses churches toward practical ways to make disciples and engage in mission. This study compares the writings of Lesslie Newbigin and Lamin Sanneh for their contributions to a theology of mission for this context, focusing on the practical implications of different ways of conceptualizing the Church’s engagement with culture. ‘Postmodern’ is used to characterize the American socio-cultural milieu, increasingly complex due to the widespread influence of postmodernist ideas, although modernity continues also as a cultural force. Problematics of this milieu include epistemological relativism, moral relativity, and suspicion of power interests. Postmodernism overlays a history of Christian influence in America, eroding under secularity yet residual in the American mythos. Newbigin’s discourse on modern Western culture, and Sanneh’s discourse on ‘mission as translation’ are compared by reference to gospel, church, and culture. Newbigin tends to reduce the gospel to a worldview because of his epistemological critique of culture, but his ecclesiology counters this. His cultural analysis is criticized as setting mission on a path that exacerbates postmodern problematics, especially suspicion of power interests. Sanneh sees Christianity as a vernacular translation movement in which receptors discover and assimilate the gospel through enacting moral responses to divine selfdisclosure. His individualistic ecclesiology is a weakness. Approaches conducive to the postmodern milieu include interpersonal relationships, the language of personal testimony and story, and dialogue centred on the biblical narrative. Newbigin’s missiology of cultural renewal, in tandem with Sanneh’s claim that missionary activity is the primary manifestation of the missio dei, with church structures as contingent arrangements, constitutes a call for a reoriention of missiology and ecclesiology. The study affirms and proposes a theology of mission directed to cultural renewal, with Bible-based dialogue a key methodology. These findings merit further research and development in practical terms.

The study explores the experiences of Access to Business students on a course that is characterised as diverse in terms of age, ethnicity and nationality. The key research question asked how students from diverse backgrounds experience learning on an Inner-City Access course. Sub-questions explored the extent to which the course attracted students from groups under-represented in higher education, how a classroom characterised as diverse affected the formation and functioning of learning communities and attitudes towards student dropout. I adopted an interpretive, naturalistic method of enquiry, theorising the Access to Business programme as a bounded system (Smith, 1978) and conducting a qualitative case study. From a review of the literature I develop a theoretical framework incorporating habitus and capital (Bourdieu, 1984); communities of practice (Lave & Wenger, 1991; Wenger, 1998) and the relationship between commitment and student dropout (Tinto, 1975). A common thread running through the framework is that of identity and difference. The main research method I employed was the semi-structured interview. Other methods included focus groups, questionnaires and meetings. As a teacher/researcher I was also able to draw on my experience of teaching the students that provided the research data. The main findings of my research reveal the way aspects of identity help to shape the way the classroom functions as a learning community: age, age difference, ethnicity, nationality and attitudes towards study play a part in the way students interact and form groups in the classroom. Diversity is seen as a resource that others can draw on to support learning. The study revealed the way the course has, to an extent, been colonised by those who have social resources that normalise participation in higher education and how aspects of learners' identities influence attitudes towards student dropout. I suggested that the Access to Business course at Inner-London College could do more to target under-represented groups in and that a practical strategy would be to integrate Access awareness raising and normalising activities into existing programmes such as 'Aimhigher'. I also considered how practitioners could improve practice by recognising the importance that identity and social participation plays in learning and suggested practical suggestions for the classroom. Finally I considered possible areas for further research.

An important consideration when designing structures from composite materials is their susceptibility to impact damage. Even under relatively low velocity impact, composites are vulnerable to internal damage caused by transverse loads, but unlike metallic structures, material damage can be hidden within the material and show no form of external damage. In some cases, barely visible impact damage (BVID) may occur, which even if detected by visual inspection would give no true indication to the severity of the internal material degradation. Since many composites are being utilised in high performance applications, it is important that the response of composites under impact loading is fully understood. This research examines the transient dynamic response of metallic and composite plates subjected to low velocity impact loading for conditions in both air and underwater by conducting a series of experiments and non-linear numerical analysis using the finite element technique. To verify the accuracy of this method for investigating impact problems, several numerical validation studies have been conducted using published results. An instrumented low velocity impact rig was used to acquire experimental data for impacts in air and underwater for both aluminium and composite plates. Experimental results were compared with numerical and theoretical solutions and found to be in good agreement. For underwater impact, the numerical modelling incorporated the use of Arbitrary Lagrange Euler (ALE) methodology, therefore, analysing the problem with coupled fluidstructure interaction. The effect of the water surrounding the target plates was found to reduce the peak accelerations and also reduce the overall impact duration. X-Ray imagery of the composite plates also showed visibly reduced damage for the submerged test specimens. This research provides data on the impact response of metallic and composite materials, and validates numerical methodologies for use in future work on fluid-structure interactions which show strong potential for relevant industrial applications.

Second order matrix equations arise in the description of real dynamical systems. Traditional modal control approaches utilise the eigenvectors of the undamped system to diagonalise the system matrices. Any remaining off-diagonal terms in the modal damping matrix are discarded. A regrettable automatic consequence of this action is the destruction of any notion of the skew-symmetry in the damping. The methods presented in this thesis use the `Lancaster Augmented Matrices' (LAMs) allowing state space representations of the second order systems. `Structure preserving transformations' (SPTs) are used to manipulate the system matrices whilst preserving the structure within the LAMs. Utilisation of the SPTs permits the diagonalisation of the system mass, damping and stiffness matrices for non-classically damped systems. Thus a modal control method is presented in this thesis which exploits this diagonalisation. The method introduces independent modal control in which a separate modal controller is designed in modal space for each individual mode or pair of modes. The modal displacements and velocities for the diagonalised systems are extracted from the physical quantities using first order SPT-based filters. Similarly the first order filters are used to translate the modal force into the physical domain. Derivation of the SPT-filters is presented together with a method by which one exploits the non-uniqueness of the diagonalising filters such that initially unstable filters are stabilised. In the context of active control of rotating machines, standard optimal controller methods enable a trade-off to be made between (weighted) mean-square vibrations and (weighted) mean-square control forces, or in the case of a machines controlled using magnetic bearings the currents injected into the magnetic bearings. One shortcoming of such controllers for magnetic bearings is that no concern is devoted to the voltages required. In practice, the voltage available imposes a strict limitation on the maximum possible rate of change of control force (force slew rate). This thesis presents a method which removes the aforementioned existing shortcomings of traditional optimal control. Case studies of realistic rotor systems are presented to illustrate the modal control and control force rate penalisation methods. The system damping matrices of the case studies contain skew-symmetric components due to gyroscopic forces typical of rotating machines. The SPT-based modal control method is used to decouple the non-classically damped equations of motion into n single degree of freedom systems. Optimal modal controllers are designed independently in the modal space such that the modal state, modal forces and modal force rates are weighted as required. The SPT-based modal control method is shown to yield superior results to the conventional notion of independent modal space control according to reasonable assessment.

A range of inorganic materials, with potential applications as inorganic pigments have been synthesised, characterised using powder X-ray and neutron diffraction (PXD, PND), UV-visible spectroscopy, electron microscopy, colour measurements and placed in context with commercially available inorganic pigments. Lanthanide chromates(V), LnCr04 (Ln=La, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb), have been prepared, as green powders, by the reaction of the component metal oxides in air. The materials adopt a zircon-type structure with the space group lAMamd, with the exception of lanthanum chromate(V) which adopts a related, but more complex, monazite-type structure in the space group P2i/n. The zircon type structure consists of LnOg polyhedra linked via discrete tetrahedra, the chromophore in these materials. The colour of the compounds in the series Pr to Yb is seen to become increasingly more yellow and lighter as the series is traversed. Analysis of PXD data using Rietveld profile fitting methods shows that the structural changes that are a result of the decreasing size of the lanthanide ions are responsible for the colour change. Contraction of the lattice parameters increases the distortion to the Cr(V)O₄ tetrahedra and at the same time a small decrease in the Cr-0 bond length. UV-visible spectroscopy identified that the combination of the ²T₂←²E transition and charge transfer bands of the Cr(V)O₄ unit imparts the green colour. Colour values for the series are comparable to the inorganic pigment chromium(III) oxide. The green alkaline earth bischromates(V), M₃(Cr0₄)₂ (M=Ba and Sr) space group R-3 m, have been prepared via conventional solid state synthesis from the component metal oxides. As with the lanthanide chromates(V), UV-visible spectroscopy identified the green colour as being derived from a combination of the ²T₂←²E transition coupled with charge transfer bands; however for these materials the colours, in terms of use as inorganic pigments, were found to be inferior to chromium(III) oxide. The space group of calcium analogue, Ca3(Cr04)2, was found to be R3c. Initial analysis of PXD data indicated that the material was calcium deficient but the collection and analysis of PND data indicated defect levels were low. The presence of three distinct chromium(V) sites in this material, and the possible mixed chromium valence resulting firom small levels of calcium deficiency, may be the origin of the black colour of this material. The reaction conditions for the synthesis of ultramarine blue from zeolites with a Si:Al ratio of unity, namely zeolites A, MAX and P, with sulphurous reagents in evacuated sealed systems have been optimised. The conversion of zeolites JEW and EDI was unsuccessful, attributed to framework density and high potassium levels in these zeolites. The effect of potassium content on shade control of ultramarine blue under the optimised reaction conditions has been investigated. The potassium ion exchange of zeolites prior to conversion to ultramarine blue produces a small increase in red shade as a fLinction of potassium content until potassium levels are detrimental to the formation of the sodalite structure. This supports the theory that in the industrial process potassium stabilises the S⁻₃ radical. A number of first row transition metal borates and copper aluminium borates have been prepared and the nature of the electronic transitions of the chromophores characterised using UVvisible spectroscopy. Colour values have been determined and compared with existing commercially available inorganic pigments. The orthoborates MBO₃ (where M= Ti and V), nickel orthoborate (Ni₃(BO₃)₂) and manganese oxyborate (Mn₂O(BO₃)) produced inferior materials, in terms of colour values, colour values of chromium (CrBO₃) and iron (Fe₃(BO₃)₂ orthoborates were comparable. Cobalt borate (Co₃(BO₃)₂), the copper(II) borates (CUB₂O₄ and Cu₁₅[(B₂O₅)₅|(BO₃)₆|O₂]) and two copper aluminium borates (Cu₂AlBO₅ and Cu₂Al₆B₄O₁₇) produced potentially alternative materials to existing inorganic pigments inviting further consideration.

Organic molecular crystals form a condensed solid phase offering a rich vein of physical phenomena which are open to investigation. The desire to harness these properties for technological and biological purposes has led to extensive experimental and theoretical investigations. The naturally occurring ɑ-amino acids form molecular crystals in the solid state; to date there have been very few studies of these systems. The work in this thesis is concerned with attempting to understand the relationship between the properties of the molecular crystal, and how these relate to the properties of the constituent molecules in isolation. To this end, density functional calculations of the structural and electronic properties of amino acids in both the crystalline and gaseous states are performed, and the results reported. The bonding mechanisms responsible for the crystal being stable are elucidated, and used to explain the zwitterionisation of the molecules upon formation of the solid state. In order to investigate the lattice dynamical and dielectric properties, the implementation of a variational density functional perturbation theory (DFPT) scheme within the plane wave pseudopotential formalism is described in detail. This scheme is fully self-consistent, and its computational cost is comparable to that of a single-point self-consistent total energy calculation. The long wave method is used to alleviate well-known problems associated with the application of homogeneous fields to crystal systems, viz. that such fields break the crystal symmetry, and the adequate treatment of electronic screening. Calculation of the first order perturbed wavefunctions and the second order change in the Kohn-Sham functional allows properties such as the polarisability, dielectric matrix, dynamical matrix and Born effective charge tensors to be determined. The treatment of crystalline symmetries is described in detail. The DFPT formalism is extended to allow IR absorption spectra to be obtained. The lattice dynamical and dielectric behaviour of the isolated molecules and the molecular crystals are obtained; calculation of the IR spectra facilitates an insight into the effects of the crystalline environment and zwitterionisation upon the lattice dynamics. Results indicate the importance of the molecular shape and structure upon the intermolecular interactions, and hence the crystal structure formed. It is these intermolecular interactions that are found to play the major part in modification of the lattice dynamical and dielectric behaviour.

The radio spectrum is the fundamental resource upon which all radiocommunication services depend. It is utilised for a vast array of different services over land, sea, air and space, and brings an enormous benefit to society. However, it also brings stringent demands for its management, at both national and international levels, in order to ensure that the services that have been allocated bands are not subjected to interference. Current methods of radio spectrum management are based around rigid, fixed allocations of bands for use by particular services. The demand for the spectrum is increasing, but the levels of spectrum available are not matching the demand. This is compounded by the convergence of radio systems, which makes the allocation of bands for precisely defined categories of service appear less relevant. Therefore, current radio spectrum management is faced with a need to improve the efficiency of spectrum use, and adapt to the challenges imposed by convergence. This thesis presents and investigates a new method for utilising spectrum that is cooperatively shared between two radio systems. Most radio systems are subject to inherent time-varying demands for their spectral resources, and it is proposed that these variations can be exploited, together with the coordination enabled through a converged multi-radio system, to improve the efficiency of spectrum usage. This is studied on several levels. A theoretical model for the potential spectrum efficiency gains achievable from the time-varying demands on the networks is derived. An algorithm is developed to reallocate the spectrum dynamically to the networks, and different aspects of this algorithm are investigated by simulation to analyse its performance. Furthermore, the impact of external factors, outside of the algorithm’s control, is studied, to observe the effect on the performance. Finally, the results of the simulated investigations are brought together, and compared to the theoretical model.

Background and Objectives: To reduce the potential for transmission of hepatitis C virus (HCV) from an RNA positive, anti-HCV negative blood donation, the National Blood Service (NBS) decided to introduce nucleic acid amplification technology (NAT) testing of blood donations for HCV in England and Wales. The objective of this thesis was to develop an automated assay using commercial components for the detection of HCV RNA in blood donations for transfusion, and to validate sample handling and storage procedures. Studies included in the thesis: The stability of HCV in the plasma sample was investigated to define the appropriate sample handling and storage conditions needed to preserve HCV RNA in the blood sample before analysis by NAT. HCV RNA was found to be more stable than previously thought, with HCV levels remaining stable for 120 hours in un-separated whole blood at refrigerated or room temperature. The compatibility of the Qiagen and Roche reagents were tested using manual assays and automated systems. This work has shown that it is possible to completely automate HCV NAT screening. Alternative techniques for virus detection such as TMA and HCV core antigen were also investigated and PCR was found superior to antigen and equivalent to TMA. The window period of the HCV infection was further defined in a study of window phase HCV samples from US plasma donors. Outcome: The combination of methods developed and described in this thesis were successfully introduced into routine use within the NBS from 1999 and are now used for release of blood components with a shelf life of greater than 24 hours in England and Wales. From 1999 to the end of 2002 approximately nine million donations were tested in England and Wales of which seven were HCV infected window phase units, which would have otherwise been transfused. In addition 394 NAT positive samples were found which were also detected by anti-HCV screening tests.

The incorporation of the sense of touch into virtual reality is an exciting development. However, research into this topic is in its infancy. This experimental programme investigated both the perception of virtual object attributes by touch and the parameters that influence touch perception in virtual reality with a force feedback device called the PHANTOM (TM) (www.sensable.com). The thesis had three main foci. Firstly, it aimed to provide an experimental account of the perception of the attributes of roughness, size and angular extent by touch via the PHANTOM (TM) device. Secondly, it aimed to contribute to the resolution of a number of other issues important in developing an understanding of the parameters that exert an influence on touch in virtual reality. Finally, it aimed to compare touch in virtual reality between sighted and blind individuals. This thesis comprises six experiments. Experiment one examined the perception of the roughness of virtual textures with the PHANTOM (TM) device. The effect of the following factors was addressed: the groove width of the textured stimuli; the endpoint used (stylus or thimble) with the PHANTOM (TM); the specific device used (PHANTOM (TM) vs. IE3000) and the visual status (sighted or blind) of the participants. Experiment two extended the findings of experiment one by addressing the impact of an exploration related factor on perceived roughness, that of the contact force an individual applies to a virtual texture. The interaction between this variable and the factors of groove width, endpoint, and visual status was also addressed. Experiment three examined the perception of the size and angular extent of virtual 3-D objects via the PHANTOM (TM). With respect to the perception of virtual object size, the effect of the following factors was addressed: the size of the object (2.7,3.6,4.5 cm); the type of virtual object (cube vs. sphere); the mode in which the virtual objects were presented; the endpoint used with the PHANTOM (TM) and the visual status of the participants. With respect to the perception of virtual object angular extent, the effect of the following factors was addressed: the angular extent of the object (18,41 and 64°); the endpoint used with the PHANTOM (TM) and the visual status of the participants. Experiment four examined the perception of the size and angular extent of real counterparts to the virtual 3-D objects used in experiment three. Experiment four manipulated the conditions under which participants examined the real objects. Participants were asked to give judgements of object size and angular extent via the deactivated PHANTOM (TM), a stylus probe, a bare index finger and without any constraints on their exploration. In addition to the above exploration type factor, experiment four examined the impact of the same factors on perceived size and angular extent in the real world as had been examined in virtual reality. Experiments five and six examined the consistency of the perception of linear extent across the 3-D axes in virtual space. Both experiments manipulated the following factors: Line extent (2.7,3.6 and 4.5cm); line dimension (x, y and z axis); movement type (active vs. passive movement) and visual status. Experiment six additionally manipulated the direction of movement within the 3-D axes. Perceived roughness was assessed by the method of magnitude estimation. The perceived size and angular extent of the various virtual stimuli and their real counterparts was assessed by the method of magnitude reproduction. This technique was also used to assess perceived extent across the 3-D axes. Touch perception via the PHANTOM (TM) was found to be broadly similar for sighted and blind participants. Touch perception in virtual reality was also found to be broadly similar between two different 3-D force feedback devices (the PHANTOM (TM) and the IE3000). However, the endpoint used with the PHANTOM (TM) device was found to exert significant, but inconsistent effects on the perception of virtual object attributes. Touch perception with the PHANTOM (TM) across the 3-D axes was found to be anisotropic in a similar way to the real world, with the illusion that radial extents were perceived as longer than equivalent tangential extents. The perception of 3-D object size and angular extent was found to be comparable between virtual reality and the real world, particularly under conditions where the participants' exploration of the real objects was constrained to a single point of contact. An intriguing touch illusion, whereby virtual objects explored from the inside were perceived to be larger than the same objects perceived from the outside was found to occur widely in virtual reality, in addition to the real world. This thesis contributes to knowledge of touch perception in virtual reality. The findings have interesting implications for theories of touch perception, both virtual and real.

The provision of healthcare services is perhaps one of the largest and most complex industries worldwide. As one of the essential necessities to sustain life, it faces the consequences of increasing demand in times of limited financial resources and competing social needs. Providing the appropriate medical care involves decision-making in terms of planning and management of healthcare resources. There is currently a great need to evolve a framework in which necessarily detailed, stochastic, flexible and user-friendly operational models, to aid both the planning and management of hospital resources, can be developed. Such a framework is considered and created within this research. Furthermore, detailed integrated simulation models for the planning and management of hospital beds, operating theatres, workforce needs and critical care services have been designed and built. An evolutionary development methodology has been adopted whereby the research work and model development has been guided by a number of steering groups within participating NHS Trust. The derived framework incorporates the need for sophisticated patient classification techniques to be adopted. In order to capture the uncertainty and variability amongst the patient population, a number of classification techniques have been considered and evaluated for their relative performances and practical usefulness. Healthcare issues representing both challenges and opportunities are explored in order to provide a basis for tentative conclusions about the current state of operational modelling for healthcare. A framework for the successful design and implementation of operational models in a healthcare environment is proposed.

This thesis describes investigations into the synthesis and secondary structural properties of novel carbohydrate-derived peptidomimetics. The syntheses from diacetone-D-glucose of five diastereomeric 3-azido-tetrahydrofuran carboxylates are described. These highly functionalised β-amino acid equivalents are accessed via the diacetone-3-azido-3-deoxy sugars and 3-azido-3-deoxy-1,4-lactones. An acid-catalysed rearrangement results in the formation of the tetrahydrofuran ring with the protected amine functionality already in place in a position β- to the carboxylate group. Attempts to synthesise "carbopeptoids" via various oligomerisation strategies, including three novel approaches to oligomerisation, are delineated. The first approach attempted involves an iterative addition of a bicyclic lactone, which acts as the activated acid component, to the substrate containing an amine functionality. A new solid-phase oligomerisation strategy, whereby the coupling reagent is tethered to the polystyrene support and the substrates remain in solution, is described. The third attempted novel oligomerisation strategy involves activation by microwave irradiation, in the absence of coupling reagents. The conventional coupling using a carbodiimide coupling reagent proves to be a highly efficient means to access oligomers up to six residues in length, and is utilised for the synthesis of the homooligomers of four diastereomeric carbohydrate-derived β-amino acids. The prospect that the carbopeptoids may emulate the helical conformations reported for closely related 2-aminocyclopentanecarboxylic acid oligomers is investigated. Different methods of spectroscopic analysis of the tetrameric and hexameric oligomers are discussed. Circular dichroism spectroscopy provides a rapid diagnostic tool for the investigation of peptide bond orientations and forms the basis for a postulation on a possible stabilised hydrogen-bonding secondary structural conformation in two tetrameric species. Several nuclear magnetic resonance spectroscopic experiments are performed, enabling the assignment of each signal in the proton spectrum for a hexameric oligomer. However the resulting data does not provide sufficient evidence for a well-defined secondary structural motif, and so the potential conformational preference postulated on the basis of circular dichroism spectroscopy is not confirmed.

In this thesis, we consider solutions u = u(t, x) for t > 0 and x e R, in time and one space dimension, of stochastic PDEs of the form dtu = Au + a(u) + b(u) dW where W is space-time white noise. The area is surveyed in Pardoux and an introduction to the concepts of white noise and SPDE solutions can be found in Walsh.

Composite honeycomb sandwich structures have been favoured in the aircraft industry for many years due to their low-weight, high stiffness, and improved fatigue resistance. The response of doubly curved, composite honeycomb sandwich panels to high intensity, random pressure loads has received little attention, and there is a need to update current design guides to include this type of structure. A set of four doubly curved honeycomb sandwich panels were manufactured at the University of Southampton. The panels were tested to determine some of the resonance frequencies of vibration, and the results were used to validate the Finite Element models of the four panels. These FE models were used to study the effects of various design parameters on the free vibration response, and the work resulted in various sensitivity parameters which could potentially be used as a guide for designers. The major part of the work involved testing the panels in a Progressive Wave Tube (PWT) facility with random acoustic excitation at grazing incidence to the concave panel surface. The measured strain response of the panels was predominantly in the fundamental bending mode, with face plate strain levels which differed between the inner and outer face plates, highlighting the significant effect that double curvature can have on the relative strain levels in the face plates. A new method was developed for estimating the shear strain in the core of the sandwich panels using a finite difference approximation. The technique was validated using a cantilevered sandwich beam, giving excellent agreement between experiment and theory for both static and dynamic response. The work resulted in a new viable technique which has potential for use in generating S/N data for the core during random fatigue testing of sandwich coupon structures.

The 'local circuits' of the mammalian neocortex are defined within cortical columns less than 1mm across. There is mounting evidence that these fine-scale neural networks are an important organisational and functional unit. However, detailed study of the local circuitry is hampered by considerable technical difficulties; computer-based modelling therefore offers an important approach to understanding their basic properties. In this thesis, computer simulations are used to examine some of the fundamental questions associated with this class of neural network. We describe a spiking-network model which is inspired by anatomical and physiological study of local neocortical circuitry. Small, heterogeneous circuits are constructed from regular firing, rhythmic bursting and fast spiking neurons. These cells interact strongly through dynamic connections; synapses exhibit facilitation, depression, or a hybrid form of non-associative plasticity. A fast, asymmetric Hebbian process is also examined as a model of the 'Malsburg synapse', and is implemented in parallel with the non-associative fonns of plasticity. Exploration proceeds in three stages using a bottom-up methodology. First, we investigate the dynamical repertoire of the individual classes of circuit; the significance of architectural variation between circuits is addressed, and we examine the influence of fast adaptive processes in shaping network dynamics. Guided by available experimental data, circuits are connected in the second stage to create larger architectures; these are used to study interactions between the circuits. In the third stage, the inhibitory circuits implement surround and feedback inhibition, and local circuit effects of these two contrasting models are explored. Simulation results offer novel links between disparate experimental data. They also indicate how variation in the architecture of particular local circuits, and the different classes of connection between these circuits, might have functional pertinence. More generally, our findings suggest how this style of network may support a highly flexible, dynamically configurable computational architecture.

Human pancreatic islet transplantation offers a potential cure for type 1 diabetes mellitus by restoring normoglycaemia at an early stage of the disease. The crucial stage of the islet isolation process is the collagenase-digestion phase. However, this process is extremely variable and also poorly understood. The aim of this thesis therefore, was to investigate the collagenase-digestion phase of human and porcine islet isolation. The first three chapters consist of reviews of islet transplantation and cell isolation and outline the problems to be addressed. Chapter 4 investigates different aspects of the variability of different batches of crude collagenase. Twelve different batches of crude collagenase were tested on both human and porcine pancreata. Clear differences were noted between collagenase digestions by the different batches and also between the two species. Chapter 5 describes a 'simple in vitro' method that was developed for testing different batches of collagenase or collagenase components on any one mammalian pancreas, thereby controlling for inter-pancreatic variability. Chapter 6 outlines the optimisation of biochemical assays for different components of crude collagenase. Chapter 7 investigates the stability of four different batches of crude collagenase under eight different storage conditions over a six-month period using biochemical assays. Chapter 8 describes a series of experiments investigating the inhibition of crude collagenase by University of Wisconsin solution. Chapter 9 evaluates the influence of different administration pressures on the distribution of collagenase within the porcine pancreas using novel methods with anti-collagenase monoclonal antibodies. Finally, the overall conclusions and suggestions for future research are discussed in Chapter 10.

This thesis records the research and development work carried out on a new telecommunications multiple-access system called the 'Complex Valued Collaborative Coding Multiple-Access' (CV-CCMA) system. The CV-CCMA system enables more than one transmission to use a communication channel without significant bandwidth expansion. The work has been completed between 1995 and 2000 whilst researching for a (part-time) Doctor of Philosophy degree at the University of Warwick. The new multiple-access system follows the general trend in communication systems that has been taking place over recent years. The reduction in the cost of processing power (million floating-point operation devices are now only a few pounds), has meant that the complex processing components of communication systems have moved from the analogue to the digital domain. Systems once regarded as too expensive to implement (except by the military) are now commonplace. The main digital processing element used for development of the system is a standard floating-point digital signal processor (DSP). A summary of the algorithm developed and software produced is included in this thesis. New techniques were developed to solve the multi-access resolution problems using the DSP and these are presented. The fundamental theory underlying the CV-CCMA system is described in detail with simplified examples showing the processes involved. A practical two-transmitter, one-receiver implementation was designed and constructed in order to prove the viability of the system, and details of this work are included in the thesis. Computer programs were written to solve the various linear algebraic equations relating to the operation of the decoding algorithm. Simulation programs enabling parameter variation without circuit construction are also recorded in the thesis. Problems encountered with the new circuitry are discussed and the solutions detailed. This includes a new high-stability oscillator that was designed, built, and tested and which was required in order for the system to function properly. Also described is the high-speed conversion circuitry. A new sequence of codewords has been developed, helping to reduce the stringent requirement on timing and synchronisation, and results are presented. New methods of synchronisation are discussed together with future development of the system. Projections as to possible uses of the system are also presented. Finally, there is a short comparative discussion of the CV-CCMA system and the broadband code division multiple-access system, recently on trial in the United Kingdom. This is of specific interest to Cable and Wireless PLC, the main sponsor of the research.

An area of particular concern is the design of electrical switchgear within embedded generation systems. Currently, the electrical design for embedded generation installations are prepared without the use of any specialist design tools, software based or otherwise. This situation renders the switchgear design process reliant upon bespoke, ill-defined and un-optimised methods. Such practices are labour intensive, error prone and require substantial expertise in all aspects of power protection and distribution systems. This thesis investigates the use of object oriented programming to develop a software tool that assists with the complete design and specification of embedded generation switchgear. By capturing the design rationale in such a tool, fast, accurate and checked switchgear designs may be produced by developers without extensive previous switchgear design experience. The thesis describes how the design process for switchgear may be rationalised based upon design methodology, taking account of legal and regulatory codes of practice, such as G59. A complete and general review of artificially intelligent techniques and programming paradigms considered suitable for capturing design reasoning are presented. All aspects of the switchgear design are modelled, including protection and instrumentation equipment, auxiliary power supplies and sundry components. Internal component section, connection and loading is automated ensuring that a complete, fully specified switchgear installation is produced. The techniques investigated illustrate that cooperating, interacting networks of software objects may be used to assist and perform switchgear design. The techniques presented could be readily adapted for use in other, non-related design domains, within which complex interdependent architectures and relationships exist.