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This thesis examines how open innovation is related to dynamic capabilities and strategic agility using an empirical approach. By adopting a microfoundations lens and examining open innovation processes, first, I develop a model to explain how open innovation is related to sensing and seizing abilities of the dynamic capability framework. Next, by considering resource bundling and individuals' activities alongside broader organisational conditions and activities, I develop a framework to further explain the relationship between open innovation and a firm's dynamic capability. Finally, to address the omission of speed from the dynamic capability literature and the development of resources and capabilities, I develop a framework to explain the interplay between open innovation and a firm's strategic agility. In doing so, this thesis advances our understanding of the open innovation concept by linking open innovation to strategic firm-level concepts. Furthermore, this thesis contributes to our understanding of the multi-level nature of open innovation by uncovering microfoundations that underlie the relationship between open innovation and strategic firm-level concepts.

Antibiotic resistance is a serious ongoing threat to both the medical and agricultural sectors, with far-reaching and diverse consequences. Historically, antibiotic resistance has been thought to be driven by the anthropogenic use of antibiotics in clinical and agricultural settings. However, there is a growing body of evidence that clearly demonstrates that antimicrobial resistance developed naturally, millions of years ago. Understanding these natural drivers of antibiotic resistance is key to managing the ongoing antimicrobial resistance problem. One potential natural driver of antibiotic resistance are phytochemicals which are chemicals produced by plants for environmental interaction. Phytochemicals are being explored for their potential role as antibiotic replacements in the clinic, and in agriculture. We propose that the use of phytochemicals as antimicrobial replacements in multiple industries will have an equal, or worse impact on the problem of antibiotic resistance, due to their potential to select for cross-resistance to other antimicrobials such as antibiotics. Phytochemicals could drive antibiotic resistance in one of three ways: (1) The selection of genes which confer cross resistance to antibiotics. (2) The selection of plasmids carrying both phytochemical and antibiotic resistance genes and (3) the selection of bacteria which are known antimicrobial resistance reservoirs. In this study, two antimicrobial phytochemicals, quercetin and berberine were explored for their role as natural drivers of antibiotic resistance. This study was split into three different experimental methodologies. The first experimental methodology developed a novel phytochemical screening assay, which was then successfully used to screen an oral metagenomic library, and the Swab and Send bacterial isolate library. Screening the metagenomic library uncovered three isolates with tolerance to either quercetin or berberine. These isolates contained inserts with multiple antibiotic resistance genes, including a glycosyltransferase and transpeptidase. Screening the Swab and Send library uncovered 20 isolates from 11 bacterial species containing antibiotic resistance genes with a phytochemical tolerant phenotype. The second experimental methodology evolved P. aeruginosa NCTC 7244 and NCTC 9433 in sub-inhibitory concentrations of the phytochemicals for 30 days. This experiment was conducted see how environmental bacteria responded to phytochemical selective pressure. Eleven of the 12 isolates developed a 2-fold phytochemical tolerance after 30 days. The isolates contained multiple genetic mutations including mutations in a glycosyltransferase and transpeptidase gene. The final experimental methodology explored the impact of phytochemical addition to chicken feed on the microbiome of chickens through two in vitro model experiments, and an in vivo chicken study. The studies also compared the viability of the two in vitro models as replacement for in vivo chicken experiments. Addition of both phytochemicals impacted microbiome development in all models compared to the control. Specifically increasing the levels of Escherichia-shigella and Turicibacter genera and decreasing levels of Lactobacillus pontis which may indicate an increase in disease incidence due to phytochemical supplementation. This study shows that berberine and quercetin can act as a selective pressure for the maintenance and mutation of genes which confer antimicrobial resistance, and the selection of antimicrobial resistant isolates in isolate libraries and the chicken gastrointestinal system. Therefore, serious consideration should be given to the risks of using phytochemicals as antimicrobial replacements in both agricultural and clinical sectors.

Older prisoners are the fastest growing prison population with the number of older offenders rapidly increasing in recent years. Whilst this trend can be seen across both male and female offenders, the overwhelming majority of older people in prison are men. Despite this, older men in prison have received limited attention within policy, practice, and academic research. Insight into how they make sense of their everyday realities in prison is particularly scant. This thesis presents a constructivist grounded theory study exploring the lived experiences of older men in prison. A total of 24 in-depth interviews were conducted with 17 older men who had experience of prison in later life, either in prison or recently released, and 7 prison officers. Central to the men's experiences of prison were the nature of the environment, their relationships, and identities, and preparing for and managing release. An overarching theoretical account was constructed from analysis of the empirical data, with two concepts central to this: prison climate and capital. The older men described various factors that came together to shape the overall feel of the prison environment, or climate, and the extent to which this was suitable for their needs as older people. Whilst there was a sense of commonality in that the prison climate was perceived as challenging and hard to navigate, the way in which it was experienced was also shaped by the presence of various individual resources, or capital. Based on this, some were afforded more ways in which to negotiate the environment and make sense of their situation constructively. This study therefore contributes an original way of understanding the experiences of older men in prison. The implications of these findings are discussed in relation to both policy and practice. The importance of a unifying policy strategy for older offenders is particularly stressed.

Since the licensing of the first monoclonal antibody (mAb) over 30 years ago, the mAb industry has expanded exponentially, with six of the top 10 blockbuster drugs in 2018 being antibody-based. However, rather than resting on their laurels, drug developers have continued to innovate. This has led to the development of 'next generation' biologics which have been designed to overcome the size and stability limitations associated with mAbs. This new era of biotechnology incorporates heavy chain only antibodies (HCAbs) such as Nanobody® molecules and VNARs, derived from camelids and sharks, respectively. Owing to their small size (~13 kDa) and reduced complexity, they are less expensive to produce than mAbs. Furthermore, their potency has been shown to be an order of magnitude higher than the best-selling mAb-based drug currently on the market, Humira®. This has enabled other methods of administration to be investigated, such as the oral, pulmonary and ocular routes. However, transdermal delivery of HCAbs has yet to be examined. Therefore, this thesis explores the transdermal delivery of both VNARs and Nanobody® molecules using hydrogel-forming microarray patches (MAPs). Using this MAP technology, both HCAbs could permeate through dermatomed (350 µm) neonatal porcine skin in vitro. Furthermore, two Nanobody® molecules were successfully delivered in a Sprague Dawley rat model for the first time. Therefore, the MAP system developed in this thesis has supported the transdermal delivery of 'next generation' biotherapeutics. This thesis also aimed to address the requests of patients from a previous study by designing a novel feedback mechanism to confirm complete MAP skin insertion. With further modification, this could help facilitate successful MAP commercialisation.

It has been estimated that 1 million people in the U.K. will be affected by dementia by 2025 with two-thirds of them being cared for at home. These informal carers are often family members who may be ill-equipped to cope with the rapidly progressive nature of the condition and thus their mental and physical well-being may be severely impacted. Literature suggests the number of sons becoming primary informal carers for a parent is increasing. These sons have unique experiences relating to the way they access support and deal with their outside relationships. Existing studies of adult-son carers have not differentiated between whether the cared-for parent is a mother or father, though this may have a bearing on understanding in this area. Gaining a better understanding of this group of caregivers and their experiences of support would help with the development of effective services for this population. This study aims to address the gap in knowledge by exploring the experiences of seven adult sons who identify as primary informal carers for a mother affected by dementia and who have accessed psychological support. Interpretative Phenomenological Analysis was the applied methodology by which transcripts from semi-structured interviews were analysed. Four super-ordinate themes were identified, namely 'Entering the world of dementia'; 'The maternal relationship'; 'Adapting to the circumstances'; and 'Receiving psychological support'. Each super-ordinate theme had sub-themes which sought to give a sense of the trajectory of the sons' experiences. The findings show sons have unique experiences in the struggle they had when they first entered the world of dementia, their coping strategies, the relationship they had with their mother and the struggle in giving cross-sex care. They also experienced an element of anticipatory grief as well as the stresses that come with their change in identity. They all valued support accessed but suggested it would have decreased their burden if it had come sooner, especially at the point of diagnosis. In the case of two participants, earlier help could have delayed the transition of their mother to a care facility. These findings should encourage the development of contextually sensitive interventions for this group of carers, who should be assessed at the point of their mother receiving the diagnosis and receive ongoing monitoring. Interventions should include grief counselling and psychoeducation on how to deal with giving cross-sex care.

This dissertation examines various aspects of normativity and representation as they figure in Kant's theory of cognition. In particular, I argue that Kant holds that certain forms of representational content constitutively depend on normative constraint. This applies to all of the kinds of content that can be captured by concepts (viz. 'kind'-properties, and the objective temporal structures that correspond to the "categories"). Since we perceptually represent objects as exhibiting these features, even the activities that produce perceptions must be normatively constrained. Nevertheless, representation per se does not depend on normative constraint: Kant holds that non-human animals can represent objects, suggesting that he endorses forms of 'non-conceptual content' that don't depend on normative constraint. Chapter 1 explores the preconditions for representing objective temporal sequence, as outlined in the Second Analogy. I argue that Kant's notion of the "necessitation of the subjective order of perceptions" must be understood as a form of normative necessity, so representations of objective temporal sequence constitutively depend on normativity. Chapter 2 continues the discussion of the Second Analogy by exploring the connection between causation and lawfulness. I argue that Kant holds that the concept of 'causation' contains the notion of lawful connection. He therefore has sound reasons for asserting the Strong Causal Principle (that every event is produced according to a universal causal law) on the basis of the Second Analogy's argument. Chapter 3 examines the role of schemata in Kant's theory of cognition. Assuming that schemata are rules for synthesis of the imagination, I argue that they should be understood as akin to maxims: mentally represented rules that bring our activities into contact with intersubjective normative standards. I argue that, by bringing synthesis under normative constraint, schemata enable intuitions to represent their objects as bearing 'kind'-properties. Chapter 4 discharges the assumption that schemata are rules for synthesis of imagination, through close reading and criticism of alternative interpretations. Chapter 5 examines Kant's views about animal minds and what they tell us about his theory of human cognition. I argue that he genuinely credits animals with intuitions of objects. Nevertheless, there are still good motivations for thinking that all human intuitions are produced by the understanding, and that it makes human and animal intuitions different in kind. The Conclusion brings together material from the preceding five chapters to discuss the extent to which Kant endorses a 'normative theory of representation'.

This thesis is a historical ethnographic study of late colonial planning and development in the racially segregated townships of a southern African city: Bulawayo, Zimbabwe (then Rhodesia). It analyses how the municipal township administration - with its high proportion of black and white social scientists, under the directorship of a noted anthropologist, Dr Hugh Ashton - executed an ambitious development drive to stabilise and improve the African townspeople. For nearly three decades, Ashton pursued a vision of creating 'modern', stratified and property-owning communities, informed by the teleological tenets of 'detribalisation', 'urbanisation' and 'modernisation' theories. This vision increasingly clashed with the Central Government's segregationist agenda to re-establish the Rhodesian city as a 'white space' in the 1960s and '70s. By systematically analysing why, and how, the Bulawayo City Council persisted with its township development vision, even under this reactionary regime, the thesis sheds light on profound ideological disjunctures within the Rhodesian state, and how the conflicts that arose therefrom reconfigured influence, expertise, and authority in the state bureaucracy. This secondary city case study contributes to the historiography of late colonial developmentalism, which refers to metropolitan and state interventions to stabilise and modernise African urban labour across colonial Africa, in response to the crises emerging from social, political and industrial changes during the Second World War. This process broadly entailed abandoning the half-hearted interwar approach to warehousing transient migrant workers, and ramping up the provision of housing, amenities and social programmes commensurate with the basic requirements of settled (albeit second class) communities. It signified an increase in the importance of upliftment and individual improvement, relative to more direct modes of control in managing the African population. The thesis contributes to this historiography, by focusing on the everyday practicalities and politics of getting things done at the local level, with scarce resources and under pressure from multiple stakeholders. It does this by analysing a significant corpus of records on the protracted negotiations, conflicts and experiments that characterised township development in Bulawayo, from municipal, national and newspaper archives. Archival research was supplemented by interviews with former 'African' and 'European' administrators, who provided insights into the institutional culture of the township administration. By thus opening the 'black box' of the colonial state bureaucracy, the thesis reveals the embeddedness of contemporary analytic and moral concepts within the everyday practical struggles of administration. This serves to counterbalance an overly functionalist interpretation of post-war development as a unitary state project of domination and consent. The study identifies three key characteristics of township development in Bulawayo that extant theories of late colonial urbanism do not adequately account for. Firstly, it was significantly decentralised. The city council spurned government expertise, tapped into regional, continental and global knowledge exchange networks, and implemented policies that often contradicted central government agendas. Secondly, the progressive developmental ideas that defined Bulawayo's particular approach were not only guides to action, but also emerged as ex post facto rationalisations for actions that were financially and administratively expedient. Thus, progressivism was wedded with pragmatism: more spatially integrated housing development reduced capital costs; extensive home ownership schemes enlisted the resources and energies of Africans; landscaped municipal beer gardens provided a significant and vital source of revenue. The resultant spectacle of impressive progress was achieved at no undue cost to either the European ratepayer or the industrial employer, and the skilful rationalisation of ad hoc, experimental decisions and compromises in terms of moral and political imperatives of modernisation imbued the development process with a sometimes misleading sense of coherent intention. Thirdly, decisions made at the critical juncture of the 1950s had strong path-dependent effects, setting Bulawayo on a trajectory from which it was increasingly difficult to diverge. The combination of these factors bequeathed a localised legacy of autonomy, self-reliance and comparatively integrated, socially stratified townships to post-colonial Bulawayo - contrasting starkly with the capital city in ways that still matter today.

This thesis explores the dynamics of knowledge accumulation from disease outbreak responses. It explores the development of a paradigm of disease outbreak response over the last 20 years, and then explains how this paradigm was challenged and re-entrenched by the 2013-2016 Ebola Crisis. The methodology for this thesis was split into two arms: a document analysis arm and an interview analysis arm. Based in an embedded case study, the document analysis makes the argument for a re-entrenchment of the paradigm through analysing the depth and detail of lessons learned from the 2013-2016 Ebola Crisis. Within this broad case, an analysis of interviews with 14 report authors and 23 report users allows for a detailed examination of the production and use of codified knowledge in disease outbreak responses. The thesis makes two primary contributions - one empirical and the other theoretical. For its empirical context, this thesis demonstrates a path-dependency in knowledge accumulation from disease outbreak responses and makes recommendations as to methods for ameliorating this. The thesis finds how a lack of meaningful engagement in expert panel processes can bias so-called lessons learned reports. In its theoretical context, this thesis contributes an additional empirical context to the literature on knowledge accumulation and learning. The thesis finds that knowledge accumulation in outbreak responses differs from other disaster scenarios because of an isolation of the Global Health epistemic community and offers evidence for codified knowledge as a useful tool and process for learning in complex, ambiguous, equivocal scenarios.

The purpose of this portfolio and thesis is to demonstrate the importance of theological reflection upon church planting practice, and by so doing, to resource and equip church planters to think in creative new ways in order to become more effective in missional engagement in forming new communities of faith. This motivation and exploration lies at the heart of each component and individual chapter. The portfolio is comprised of three self contained and coherent pieces of work: a literature review which advocates that theological reflection is a developing concern for church planting, a publishable article that reflects on the nature of the gospel that underpins missional practice, and a research project which aimed to discover how different church planting tribes were engaging in theological reflection, and what issues and lessons were still needing to be learned and further explored. The thesis, building on the work of the portfolio, gives an extended Trinitarian theological reflection upon church planting practice in relation to the themes of creation, context and community. It has attempted to intentionally reflect upon the missional practice of church planting through Trinitarian perspectives, in order that it may be more robust, enriched and rooted in God's own life and story. Trinitarian perspectives on church planting are at best embryonic, and the renewal of interest in the doctrine of the Trinity has stimulated me to write a Trinitarian missiology for church planting that offers fresh theological insights and practical missional applications. Through dialoguing extensively with the Trinitarian creation theology of Jürgen Moltmann, the Trinitarian contextual missiology of Lesslie Newbigin and Timothy Tennent, and the Trinitarian ecclesiologies of Miroslav Volf, Leonardo Boff and Catherine Mowry LaCugna, I believe their collective contributions have much to offer church planting today.

Wet age related macular degeneration (wet AMD) is a highly debilitating retinal disease, the third leading cause of blindness in the world and one the most expensive ocular conditions to care for. Wet AMD is characterised by the proliferation of neovasculature through the retinal posterior and theorised to be, at least in part, induced and driven by excess vascular endothelial growth factor (VEGF). Many current treatments for wet AMD utilise anti-VEGF macromolecules that bind to VEGF. The retina, however, remains a largely inaccessible, and delicate, anatomical region. Due to difficulties in collecting clinical and experimental data, mathematical modelling is playing an increasingly prominent role in understanding the distribution (Pharmacokinetics, PK) and drug-to-target interactions (Pharmacodynamics, PD) for treatments of wet AMD. This thesis will focus on ordinary/partial differential equation (ODE/PDE) models for the PK/PD of anti-VEGF therapeutics, administered via intravitreal (IVT) injection into the mammalian eye. We start in Chapter 2 with a 2-compartment PK/PD ODE model of drug-VEGF interactions in the eye, analysing a clinical dataset to estimate key binding parameters between VEGF and the typical anti-VEGF molecule, ranibizumab. In Chapter 3, we extend the PK ODE framework of the 2-compartment model to include a mechanistic description of the retina, to estimate retinal permeability to macromolecules used for treating wet AMD. In Chapter 4, using the retinal PK model, we reintroduce VEGF to predict concentrations of free VEGF in the retina post-IVT injection. Chapters 5 and 6 model a hypothetical class of anti-VEGF molecules designed to bind not only VEGF but also existing vitreal superstructures, analysing how dose and binding kinetics impact ocular retention. Alongside these models we present analogous PDE models, addressing whether the assumption that concentrations are homogeneous across anatomical regions, as implicit in ODE models, is appropriate for macromolecular PK/PD in the mammalian eye.

Guilt, forgiveness, and reconciliation are fundamental themes in human musical life, and this thesis investigates how people articulate these experiences through musical performance in contemporary genres. I argue that by participating in performances, individuals enact social narratives that create and reinforce wider ideals of music’s roles in society. I assess the interpenetrations of music and guilt, forgiveness, and reconciliation through a number of case studies spanning different genres preceded by a brief introduction to my methodology. My analysis of Arnold Schoenberg’s A Survivor from Warsaw illustrates the themes (guilt, confession and memorialisation) and approach I adopt in the three main case studies. My examination of William Fitzsimmons’s indie folk album The Sparrow and the Crow, investigates how ideals of authenticity, self-revelation, and persona structure our understanding of the relationship between performer and audience in confessional indie music. Analyses of two contemporary choral settings of Psalm 51 by Arvo Pärt and James MacMillan examine the confessional relationship between human beings and God. I suggest that by transubstantiating the sacramental traditions of confession in pieces designed for the concert hall, these composers navigate the boundary between the aesthetic and the sacramental. Lastly, I contrast two pieces connected to reconciliation efforts in Australia and South Africa: I argue that the unified narrative of healing in Kerry Fletcher’s “Sorry Song” becomes a performative communal apology, whilst the fragmented, multi-vocal narrative of Philip Miller’s REwind: A Cantata for Voice, Tape and Testimony illustrates how reconciliation may be achieved through constructing a collective history that acknowledges the multiplicity of testimony in post-apartheid society. I conclude that these pieces provide a means for people to enact narratives of guilt, forgiveness, and reconciliation and point towards new areas of study on the multivalent relationship between contemporary music and memory.

Neuropathies are common, yet the pathogenic mechanisms of many remain incompletely understood. Animal and cell models have provided much useful information about disease mechanisms, and yet translation of this knowledge to clinical practice and disease therapies is often disappointing. One of the difficulties in studying human nerves is limited availability of tissue, due to the morbidity of peripheral nerve (usually sural nerve) biopsy. I sought to evaluate the utility of cutaneous nerves, both generally as a tool to assess the relevance of pathogenic mechanisms identified in animal studies in human disease, and also specifically in evaluating whether immune changes in the skin may play a role in the development of neuropathic pain. Animal models have suggested that proinflammatory cytokines exert algesic effects on nerves, whilst anti-inflammatory cytokines have a counter-regulatory analgesic effect (Üçeyler et al., 2009). More recently, support for a link between variability in systemic and / or local cytokine balance and pain in neuropathy has begun to emerge (Üçeyler et al., 2007c, Üçeyler et al., 2010). Despite some support for a link between painful neuropathies and increased inflammatory and / or decreased antiinflammatory cytokines, it remains unclear whether the immune changes reflect underlying neuropathological processes, a response to nociceptor activation, variability in individual immune response to nerve damage or are a biomarker of another factor indirectly modulating both pain and immune function. It is also unclear whether immune-nerve interactions are unidirectional or bidirectional: does increased nociceptor firing modulate local immune function or does immune response to nerve damage modulate activity of remaining undamaged fibres, or is there a combination of these factors? I sought to understand the effect of acute nociceptor activation on skin immune profile, as well as whether changes in chronic neuropathy would be associated with the presence and intensity of pain.

This is an ethnographic study conducted over an 18-month period by the researcher who is a serving detective constable, working as part of a project aimed at reducing ‘top tier’ organized criminal behaviour in the MPS. The research was an exploration of how organized criminals are defined, particularly during disruption panels aimed at measuring law enforcement successes. The study examines the process by which ancillary orders are obtained at court; tools designed to restrict organized criminal activity. The study aimed to critically assess the wider monitoring process, looking at whether disruptions to offenders’ activities can be seen as durable or effective; whether ‘Lifetime Offender Management’ is successful in implementing changes in their offending behaviour. This has been set against a backdrop of literature which provides a historical context of how organized crime has come to be defined in a hierarchical fashion, that is overly focused on individuals rather than activities. It discusses how unhelpful this is as a paradigm against which to compare British organized crime. The study highlights more appropriate ‘business models’ of organized criminal offending. Within this, comparisons are made with regard to different criminals’ varying ability to launder money, versus those that operate on a more hand to mouth level. A critical look is taken at the way the disruption panels fail to make any distinction between these behaviours, as well as the way police culture informs the process of labelling organized criminals. This is by virtue of its adherence to anachronistic and outmoded models of organized criminal offending, resulting in an undue focus on certain offences and a failure to appreciate the evolving nature of the field. A gap in the literature and research is highlighted when it comes to organized crime prevention, particularly where ‘disruptions’ are concerned, presenting increased opportunities for this type of research.

This thesis is concerned with studies and analysis methods for white-light and extreme ultraviolet observations of the solar corona, including coronal mass ejections (CMEs) and other dynamic activity therein. The solar corona is a hot (∼1MK) magnetised plasma, and is host to many dynamic processes. CMEs are the largest and most dynamic phenomena that originate from the Sun, and can be observed in the extended corona by white light coronagraphs. CMEs are huge eruptions of magnetised plasma which possess a broad range of masses and outflow speeds. These eruptions and their associated bursts of energetic particles can cause adverse space weather at Earth. The 3-part appearance of many CMEs arising from erupting filaments emerges from a large magnetic flux tube structure, consistent with the form of the erupting filament system. Other CMEs arising from erupting filaments lack a clear 3-part structure and reasons for this have not been researched in detail. Chapter 3 aims to further establish the link between CME structure and the structure of the erupting filament system and to investigate whether CMEs which lack a 3-part structure have different eruption characteristics. A survey is made of 221 near-limb filament eruptions observed from 2013/05/03 - 2014/06/30 by EUV imagers and coronagraphs. 92 filament eruptions are associated with 3-part structured CMEs, 41 eruptions are associated with unstructured CMEs. The remaining 88 are categorized as failed eruptions. For 34% of the 3-part CMEs, processing applied to EUV images reveals the erupting front edge is a pre-existing loop structure surrounding the filament, which subsequently erupts with the filament to form the leading bright front edge of the CME. This connection is confirmed by a flux-rope density model. Furthermore, the unstructured CMEs have a narrower distribution of mass compared to structured CMEs, with total mass comparable to the mass of 3-part CME cores. This study supports the interpretation of 3-part CME leading fronts as the outer boundaries of a large pre-existing flux tube. Unstructured (non 3-part) CMEs are a different family to structured CMEs, arising from the eruption of filaments which are compact flux tubes in the absence of a large system of enclosing closed field. Chapter 4 presents a new, automated method of detecting CMEs in three dimensions for the LASCO C2 and STEREO COR2 coronagraphs. By triangulating isolated CME signal iv from the three coronagraphs over a sliding window of five hours, the most likely region through which CMEs pass at 5R is identified. The centre and size of the region gives the most likely direction of propagation and approximate angular extent. The Automated CME Triangulation (ACT) method is tested extensively using a series of synthetic CME images created using a wireframe flux rope density model, and on a sample of real coronagraph data; including halo CMEs. The accuracy of the angular difference (σ) between the detection and true input of the synthetic CMEs is σ=7.14◦, and remains acceptable for a broad range of CME positions relative to the observer, the relative separation of the three observers, and even through the loss of one coronagraph. For real data, the method gives results that compare well with the distribution of low coronal sources and results from another instrument and technique made further from the Sun. The true 3D-corrected kinematics and mass/density are discussed. The results of the new method will be incorporated into the CORIMP database in the near future, enabling improved space weather diagnostics and forecasting. Chapter 5 concerns observations of the extended white light corona during a total solar eclipse. Using data from the total solar eclipse of 2015 March 20 at 10:10:40 UT on the Norwegian archipelago of Svalbard, a temperature map of the solar corona is created, which accurately calculates the temperature of the solar corona out to 2R. This is achieved using ratios of the Fe XI (789.2 nm) and Fe XIV (530.3 nm) spectral lines, which are cross-calibrated with the total brightness observations of the Large Angle Spectrometric Coronagraph (LASCO) instrument C2 on board the Solar and Heliospheric Observatory (SOHO). This is a powerful tool for diagnostics of the coronal holes present during the eclipses. The temperature at the base of the corona is an important parameter for the modelling of the solar wind. Using the map, a temperature of 1.2 × 106 K is observed within the northern polar coronal hole. By applying a spherically symmetric inversion of brightness along the line of sight to the eclipse total brightness observations, the electron density as a function of height is derived. By combining the eclipse observations with LASCO C2 observations, electron density is found to be 7 × 107 cm−3 at the base of the corona, descending to 1 × 104 cm−3 at 6R. Considering conservation of mass flux, the velocity and acceleration of the solar wind outflow are also derived. Using these values estimates are also made for proton temperature within the coronal hole. The outflow velocity is found to peak at 430 km.s−1 , and acceleration at 96 m.s−2 . Fitting the density and velocity results to a Gaussian plus a 1st order degree polynomial function of height gives a robust estimate for proton temperature. Fitting returns a high peak in proton temperature of 2.5 MK, implying that wave-particle interactions are also working to drive the solar wind from the coronal hole as well as the thermal pressure gradient. An overview of the method and implementation is given. Under certain conditions large enough CMEs may cause widespread damage to satellites and other important infrastructure. The ability to predict the occurrence of a CME, and to v predict their subsequent evolution, depends critically on understanding the dominant physical processes which occur in the corona. The work presented in this thesis aims to enable the improvement of space weather diagnostics and forecasting capabilities.

Nuclear data are the foundation of simulation and design in the nuclear industry. The success of commercialising thermonuclear fusion will be based on a set of highly accurate simulations used in design, optimisation and safety analyses. This work focuses on the often overlooked, pre-processing stage of nuclear data. The effect of legacy methods in a fusion context is a concern within the community, but has never been quantified. The sensitivity of fusion neutronics to pre-processing was determined using a set of codes and methods developed as part of this thesis. Legacy pre-processing methods demonstrated a difference between the processed and unprocessed distributions of up to 20%. Simple Monte-Carlo radiation transport simulations exhibited sensitivity within energy distributions for small models (< 5 mfp). Alternative data formats did not improve simulation results sufficiently to justify their implementation. Complex, fusion specific models showed a general insensitivity to the pre-processing when run to the current levels of statistical precision. Future recommendations are to process all future data libraries into the cumulative tabulated probability format. Improved methods are not required at this stage as the core data libraries are incomplete and sometimes inaccurate. Only after the libraries have improved will pre-processing become significant.

This thesis mainly focuses on the dust content in nearby galaxies, whilst also probing the underlying stellar populations. Our main target is the nearby starburst galaxy M82. Five additional nearby galaxies are included in the final chapter. Using NUV and optical photometry, along with FUV, Hα and 8µ data, we explore the radial dependence of the dust properties. We model the dust attenuation law using a prescription that parameterises the total-to-selective extinction ratio (RV ) and NUV bump strength (B). We also include the colour excess as a parameter describing the amount of dust. By comparing with stellar population synthesis models, we show that it is possible to marginalise over nuisance parameters such as the age or metallicity of the populations. We find a significant radial trend of the dust-related properties both in M82 and the other galaxies, although there is a large variance of this trend among them. Remarkably, we find that M82s data does not match the "Calzetti" attenuation law (applied to starburst galaxies). In fact the analysis favours a law with a significant NUV bump. As a function of radius, we find that B and RV decrease outwards, with a Milky-Way like behaviour in the central region and a steeper (lower RV ) wavelength dependence in the outer regions. We explore this trend in the other five galaxies, finding a large variation in the radial trends from galaxy to galaxy, revealing the complexity of the dust properties.

T helper cells of the immune system are critical in mediating immune responses in the lung. Through the release of cytokines, T helper cells direct the wider immune response against a range of pathogens and are considered indispensible for effective immunity. T cell activation is governed by the interaction with antigen-presenting cells (APCs), which mediate antigen-specific T cell activation and thus control immune responses in areas such as the lung. While T helper cell activation by APCs such as dendritic cells is well established, the role of fibroblasts in T helper cell activation in the lung is poorly understood. Fibroblast antigen presentation was hypothesised to be a mechanism leading to activation of bacterial-specific lung T helper cells. Characterisation of T cell populations within the human distal lung was carried out. focusing upon examining the memory T cell populations. In addition, the cytokine production profile of T cells as a whole population and in response to specific lung bacterial antigen was examined. Distal lung T cells were primarily CD4 T helper cells of an effector memory phenotype. IFNγ producing, Th1-type cells were the most abundant effector subset present in all T cell populations examined, while initial responses to the common lung bacteria nontypeable haemophilus influenza were more heterogeneous. Human lung fibroblasts obtained from the distal lung were examined for expression of immune synapse molecules both ex vivo and in vitro using flow cytometry. The ability of lung fibroblasts to internalize environmental antigen was also investigated via flow cytometry and confocal microscopy. Using autologous lung fibroblasts and T helper cells, the ability of fibroblasts to present bacterial antigens non-typeable haemophilus influenza was examined. T helper activation was measured via the production of cytokines associated with the major T helper effector subsets. Lung fibroblasts expressed HLA-DR ex vivo, and were shown to upregulate HLA-DR and ICAM-1 by IFNγ treatment in vitro, but did not express CD80 or CD86. Fibroblasts were also able to internalize environmental antigen. Fibroblasts exposed to both IFNγ and a heat-killed form of non-typeable haemophilus influenza are shown to activate IFNγ and IL-17A producing T helper cells in an antigen dependent manner. This study demonstrates that lung fibroblasts are able to function as an inducible APC and activate proinflammatory T helper cells. This previously unknown relationship between fibroblast and T cell may represent a key mechanism in lung immune responses to bacterial populations.

This thesis examines topographical art depicting Scotland’s natural scenery and built environments, architecture, antiquities and signs of modern improvement, made during the period 1660 to 1820. It sets out to demonstrate that topography and topographical art was not exclusively antiquarian in nature, but ranged across various fields of learning and practice. It included the work of artists, geographers, cartographers, travel writers, poets, landscape gardeners, military surveyors, naturalists and historians who were concerned with representing the country’s varied, and often contentious, histories within an increasingly modernising present. The visual images that are considered here were forms of knowledge that found expression in drawings, paintings and engravings, elevations, views and plans. They were made on military surveys and picturesque tours, and were often intended to be included alongside written texts, both published and unpublished, frequently connecting with travels, tours, memoirs, essays and correspondence. It will also be argued that topography was a social practice, involving networks of artists, collectors, publishers and writers, who exchanged information in drawings and letters in a nationwide, and often increasingly commercial enterprise. This thesis will explore some of the strands of such a vast network of picture-making that existed in Scotland, and Britain, between 1660 and 1820, as visual images were circulated, copied, recycled and adapted, and topographical and antiquarian visual culture emerges as a complex, synoptic form of inquiry.

This thesis analyses the responses of Irish writers and painters to a phase of national self-assertion that had arguably lost its liberating potential. It shows how the exhaustion of revolutionary pressures in Ireland after independence complicates the ties between creative activity and political activism. Drawing on a wide range of scholarship within political theory, literary criticism and art history, I chart an emerging network of literary and artistic techniques that confronts the representational aesthetics of the nation with strategies of paradox, reversal and renewal. My readings of the work of Denis Devlin, Samuel Beckett, James Joyce, Mainie Jellett, Jack Butler Yeats and, in particular, Thomas McGreevy, provide a means by which to distinguish other cultural possibilities that were imagined and pursued from 1922 to 1941, including McGreevy’s own aspiration to remould 'A Cultural Irish Republic'. The thesis argues that Ireland's political and artistic avant-garde were forcibly divided during this period: two factions that had been split apart by the effects of civil war and censorship. As such it will be preoccupied with a central question: how to sustain cultural strategies of revolutionary significance when the frontier between creative activity and political activism can no longer be straightforwardly crossed.

Due to the increasing demand in Biotherapeutics, this thesis focussed on investigating novel ways to exploit major signalling pathways to enhance recombinant protein production (rP) in yeast and CHO cell expression systems. The expression of model recombinant proteins in yeast allowed us to screen for specific targets located within important environmental signalling pathways for effects upon recombinant protein production. Targets identified within the yeast system and that were conserved were then tested within CHO cell expression system. One of the systems investigated with regards to rP production was target of rapamycin (TOR) pathway. TOR signalling is a global regulator of nutrient sensing and energy status. It is a highly conserved Ser/Thr protein kinase pathway which is involved in processes such as protein synthesis, ribosome biogenesis, cell cycle, gene transcription, autophagy, and metabolism. As TOR is heavily involved in the control of protein synthesis, we asked whether it could be manipulated to enhance recombinant protein production (rP). We identified that TOR mediated amino acid sensing and autophagy are important for maintaining rP production in both yeast and CHO cells systems. Previous work supporting this thesis suggests that the actin binding protein cofilin can be manipulated to enhance both mitochondrial function and environmental sensing. We hypothesised that Cofilin functions may be useful in maintaining mitochondrial function during the stress imposed by rP production. Using a library of Cofilin strains expressing mutant alleles, we found that the control of MAPK signalling, and in particular the downstream effector Ste12, and mitochondrial functionality have a significant effect on GLuc expression when driven by the mating factor signal sequence. Manipulation of mitochondrial function or STE12 function also led to changes in rP production. In many case changes in Gluc expression or secretion were not replicated in a separate Killer toxin secretion system. As we did not see the same effects in alterations to killer toxin secretion, we concluded that these findings were specific to the presence of the signal sequence from the mating alpha factor. The manipulation of MAPK signalling and mating factor signal sequence driven secretion would appear to be a promising avenue for further enhancement of the yeast system. This work highlights the complex nature of manipulating signalling networks to achieve improvements in rP yield. However a better understanding of the mechanisms involved and the ability to manipulate these changes/responses will be beneficial for enhanced protein production from yeast and mammalian expression systems.

Social network sites (SNSs) have become very popular, with more than 1.39 billion people using Facebook alone. The ability to share large amounts of personal information with these services, such as location traces, photos, and messages, has raised a number of privacy concerns. The popularity of these services has enabled new research directions, allowing researchers to collect large amounts of data from SNSs to gain insight into how people share information, and to identify and resolve issues with such services. There are challenges to conducting such research responsibly, ensuring studies are ethical and protect the privacy of participants, while ensuring research outputs are sustainable and can be reproduced in the future. These challenges motivate the application of a theoretical framework that can be used to understand, identify, and mitigate the privacy impacts of emerging SNSs, and the conduct of ethical SNS studies. In this thesis, we apply Nissenbaum's model of contextual integrity to the study of SNSs. We develop an architecture for conducting privacy-preserving and reproducible SNS studies that upholds the contextual integrity of participants. We apply the architecture to the study of informed consent to show that contextual integrity can be leveraged to improve the acquisition of consent in such studies. We then use contextual integrity to diagnose potential privacy violations in an emerging form of SNS.

Chapter one gives an introduction into heteroborane chemistry focussing on the areas of icosahedral and supraicosahedral (metalla)carboranes and their isomerisation mechanisms. Chapter two describes attempts at placing bulky substituents onto a 1,7-closo-C2B10 species so that upon reduction and subsequent oxidation the carbon atoms are unable to connect thus potentially preventing oxidation and allowing for easier capitation to form a supraicosahedral carborane. Initial efforts to synthesise such 1,7- bulky species, using tertiary alcohol substituents, did not lead to polyhedral expansion due to undesired reactivity. Compounds with bulky substituents incorporating cobaltacarborane clusters were successfully prepared but in insufficient yield for further expansion chemistry. Chapter three discusses the synthesis and characterisation of 1,7-closo-C2B10 species which incorporate a ferrocenyl unit on each substituent. Polyhedral expansion to form a 13-vertex carborane was unsuccessful, instead upon oxidation forming significantly sterically deformed 1,2 species with unprecedentedly elongated C-C connectivities. Chapter four investigates the redox chemistry of the ferrocenyl 1,2 and 1,7 species. The electronic spectrum of the 1,2 species were compared to that given by TD DFT calculations which suggest a degree of charge transfer. Associated electrochemistry suggests this may be a sterically-induced charge transfer within the 1,2 species. The steric deformation of the bis-ferrocenyl 1,2 species leads to a relatively lowtemperature isomerisation to the 1,7 species. This has renewed interest in the elucidation of the isomerisation mechanism of icosahedral carboranes. Chapter five details the synthesis and characterisation of labelled species with labels which can be reliably tracked upon isomerisation. A comparison of the experimental findings to the results of theoretical studies on the subject is examined. Chapter six contains experimental procedures and characterisation details for all the new compounds reported herein. Crystallographic data is listed in Appendices A and B (CD) along with structure solution and refinement details.

The key aims of this thesis were to investigate the role of social support and marriage in adjustment and recovery in coronary heart disease (CHD). Declining death rates in CHD due to medical and surgical advances combined with increasing prevalence rates have contributed to a large and steadily growing population of chronic CHD patients, many of whom have suffered an acute cardiac event. In the context of this population, there is considerable need to determine factors that improve both adjustment and prognosis. Aspects of social support and marriage have been robustly associated with morbidity and mortality in CHD. Exploration of the potential psychological and biological pathways that link these factors forms the core of this thesis. Data from two separate studies are presented with the majority of analyses originating from data gathered in the Tracking Recovery after Acute Coronary Events (TRACE) study, a longitudinal study exploring diverse correlates of adjustment and recovery in 298 ACS patients. Associations between social support, marital satisfaction, distress, quality of life and HRV among ACS patients followed up from hospital admission to 12 months following discharge are presented. Data were also derived from a second study which explored psychobiological factors in a sample of 88 suspected coronary artery disease (CAD) patients and the analysis focused on marital influence on HRV. The overall thesis objective was to identify significant relationships between social and marital support, and various psychobiological factors that may contribute to adjustment and, ultimately, influence CHD prognosis.

This thesis contains the results of studies into the causes of variability seen in the optical and X-ray emission from matter accreting onto supermassive black holes (SMBHs) in active galactic nuclei (AGN). The first chapter provides a brief overview of the history of optical and X-ray astronomy along with a summary of the principle properties of AGN. The second chapter investigates the dust-to-gas relationship for a sample of 1,201 X-ray detected quasars. We carry out an in-depth optical and X-ray spectral analysis and produce composite spectra for gas absorbed and dust reddened quasars. We find that the objects with the largest gas column densities are not the objects with the largest amounts of dust reddening. This study also highlights problems in constraining absorption levels in objects with low-quality X-ray spectra. We then present optical-to-X-ray spectral energy distributions (SEDs) for 170 Type 1 AGN. We use a new broadband SED model, which combines the standard disc emission with low- and high- temperature Comptonisation components through the introduction of a coronal radius. We find that objects that have an Eddington ratio greater than unity have larger disc luminosities, lower black hole mass, higher mass accretion rate and smaller coronal radii, than the rest of the sample. We conduct a detailed optical and X-ray variability study on a subset of 41 of these objects in the fourth chapter. We combined optical light curves from the Catalina Sky Survey (CSS) with long duration X-ray observations from the XMM-Newton satellite. We found that the objects with the lowest black hole masses were the least variable. However, we did not find the expected relationship between luminosity and variability, probably due to the wavelength range observed by CSS and selection biases in our sample. The final two chapters report results from pilot studies based on data from the Pan-STARRS telescope. In the fifth chapter we present an in-depth study of a highly variable object discovered as part of the Pan-STARRS supernovae search, and in the sixth chapter we investigate a subset of the light curves produced in the Medium Deep Survey (MDS) by analysing the light curves of 39 quasars including 12 broad absorption line quasars (BALQSOs). Finally, we also examine the potential for future studies, by cross-matching a large sample of spectroscopically identified Seyfert 2 AGN to the large area 3π catalogue.

During the latter decades of the nineteenth and opening decades of the twentieth century the Roman Catholic Church in England began, slowly and in small stages, not only to adapt its self image but also to make amendments to perceptions held by outsiders as to what it stood for as an institution, what motivated its leaders and membership and what issues it regarded as important, not only in respect of its own faithful, but also in civil society at large. Its days of being a quietist, self-effacing and unstructured remnant of past times, still cowed by memories of penal times, were over. Too often the historiography of English Catholicism during the second half of the nineteenth century has been dominated by discussion of the residue of anti-papal prejudice, high-profile conversions from the Established Church, criticism of Irish immigrants and the fear engendered amongst non-Catholics by the supposed civil disloyalty of Catholics occasioned by misconceived notions of what allegiance was owed to the pope. These approaches did not look at what the English Catholic Church itself thought was important, the matters to which it chose to devote its energy and topics to which it chose to add its voice. While Catholic writers still considered doctrine, the development of liturgical style and the logistics of building up a parochial structure sufficient to support the needs of rapidly inflated congregations, there was at the same time a growing awareness of the temporal concerns of secular society, the material wellbeing of the faithful as well as the economic problems and social injustices thrown up by post-industrial, urbanized, poverty stricken and, potentially, alienated dispossessed sections of society. The thesis charts the development of a Catholic social programme by the examination of four key subject areas of work, socialism, education and social action, through the methodology of an Weberian Ideal Type construct. It poses the hypothesis that the foundation of a new era of Catholic social thought was laid between c.1880 and c.1914.

The incidence of sensory processing difficulties (SPDs) was investigated for pupils (aged 4-10 years old) with behavioural, emotional or social difficulties (BESD). Teachers provided a measure of BESD using The Strengths and Difficulties Questionnaire. Parents completed The Short Sensory Profile (SSP) and teachers completed The Sensory Profile, School Companion (SC). Data were analysed for 144 children. When total scores were calculated for the sensory measures, parents and teachers rated that 55% and 44% of the sample respectively, had sensory processing difficulties. Both parents and teachers demonstrated concerns about difficulties with overactivity, poor listening and concentration skills. Associations were found between SPDs and some background factors including anxiety and poor peer relations. When individual cases were examined, it was found that children were often rated as having difficulties at school but not at home or visa versa. The implications of this finding are discussed in relation to previous studies that have purely relied on the Short Sensory Profile, a brief parental measure of SPDs. It was cautiously concluded that the data suggest that within the BESD sample it was possible to identify a subgroup of children who may also have difficulties with sensory processing. It is suggested that it may be helpful for there to be an increased awareness of possible sensory difficulties for some BESD children among educational psychologists.

Interest and utilisation of polycrystalline boron-doped diamond (pBDD) as an electrode material has rapidly grown over the last decade, due to its unique properties and advantages over other available electrode materials. The possibility of lower detection limits and an increased range of detectable analytes has seen pBDD flourish in electroanalysis. Due to its stability at high temperatures, pressures and acidity, pBDD also has the potential to perform electrochemistry in extreme conditions. These unique properties, however, make the material difficult to manipulate in order to produce well defined and reproducible electrodes. Deviations in electrical and electrochemical responses can also arise from sample to sample, due to differing synthesis conditions and experimental set-ups. This thesis aims to characterise pBDD available from a commercial source and through fabrication of electrodes of various designs, best utilise the material in the electroanalysis of several species. Characterisation is performed using high resolution microscopic and spectroscopic techniques which show a heterogeneous material with negligible levels of non-diamond like carbon and boron concentrations of at least 1 x 1020 atoms cm-3 throughout. Disc electrodes, fabricated using laser machining, are electrochemically characterised showing low background currents, wide solvent windows and close to reversible behaviour for Ru(NH3)6 3+/2+, IrCl6 2-/3- and Fe(CN)6 3-/4. Functionalisation of these pBDD disc electrodes with nanoparticles enables the detection of dissolved oxygen and glucose to detection limits of ~ ppb. Furthermore, the fabricated electrodes are used in the study of Pb deposition and stripping behaviour at a pBDD surface, as well as Pb2+ detection. The last chapter in this thesis details the next step in diamond electrode development; the fabrication of all-diamond electrodes, where the pBDD is insulated with intrinsic diamond. Two electrode geometries are described, the first being a tubular flow ring electrode which has well-defined hydrodynamics and is used in the detection of dopamine. The second all-diamond geometry is a dual band electrode which it utilised as a solution conductivity sensor.

A binary low-density parity-check (LDPC) code is a linear block code that is defined by a sparse parity-check matrix H, that is H has a low density of 1's. LDPC codes were originally presented by Gallager in his doctoral dissertation [9], but largely overlooked for the next 35 years. A notable exception was [29], in which Tanner introduced a graphical representation for LDPC codes, now known as Tanner graphs. However, interest in these codes has greatly increased since 1996 with the publication of [22] and other papers, since it has been realised that LDPC codes are capable of achieving near-optimal performance when decoded using iterative decoding algorithms. LDPC codes can be constructed randomly by using a computer algorithm to generate a suitable matrix H. However, it is also possible to construct LDPC codes explicitly using various incidence structures in discrete mathematics. For example, LDPC codes can be constructed based on the points and lines of finite geometries: there are many examples in the literature (see for example [18, 28]). These constructed codes can possess certain advantages over randomly-generated codes. For example they may provide more efficient encoding algorithms than randomly-generated codes. Furthermore it can be easier to understand and determine the properties of such codes because of the underlying structure. LDPC codes have been constructed based on incidence structures known as partial geometries [16]. The aim of this research is to provide examples of new codes constructed based on structures known as semipartial geometries (SPGs), which are generalisations of partial geometries. Since the commencement of this thesis [19] was published, which showed that codes could be constructed from semipartial geometries and provided some examples and basic results. By necessity this thesis contains a number of results from that paper. However, it should be noted that the scope of [19] is fairly limited and that the overlap between the current thesis and [19] is consequently small. [19] also contains a number of errors, some of which have been noted and corrected in this thesis.

Roads and routeways, whether engineered or created ad hoc, create a dynamic element to the lives of those who use them and facilitate many features of day to day life. As such they have been a fundamental and powerfully ideological part of human existence. This thesis shows the causes and effects of road and transport network development in County Durham in the period from 1530 to 1730, and challenges the commonly made assertion that routes changed little from the Medieval period until the Industrial Revolution. Drove routes, lead mining routes and the infrastructure of re-used Roman roads are viewed holistically and considered as individual and integrated networks over a broad time period. These networks are analysed and compared using quantitive spatial analysis and GIS (Geographic Information System) techniques to examine which factors were pivotal in the creation of each road or routeway system. In addition, factors such as consumption patterns, shifts in population and funding mechanisms are drawn upon to examine roads as artefacts and cultural markers. Thus the roads and the roadscapes are used to study the identities of those who used them. A trial of dating techniques with which to date roads, with the use of optically stimulated luminescence (OSL) infra-red stimulated luminescence (IRSL) and radiocarbon dating, was also completed. It will be shown that different factors influenced the placement of the different routes. Distance and slope being of prime importance for the Roman network; land use type, distance and visibility for the drove routes and land use type and slope for the lead routes. These routes formed part of an holistic network which, through using different network types for different tasks and purposes, gave strength to the overall transport system of County Durham. Thus the network helped to drive new aspirations and patterns of consumption, facilitated the exchange of information and fashions and helped to provide new sources of wealth. The connectivity that the roads and routeways brought created a county with greater geographical, cultural and social knowledge that stimulated an increase in class consciousness, in so doing they also provided the means by which these new ideals and ideas could be expressed.

This thesis is a sociological historiography which is concerned with human networks and how these evolved and adapted to social change and dislocation in the eighteenth century. The experiences of several Campbell kinship groups who comprised a stratum of minor landed elites in the southwest Highlands are explored and analysed and particularly with regard to the extent to which their network structures assumed a predominantly horizontal spread. This structural alteration was a result ofthe absorption of exogamous ties and also a tendency for interest groups and professional configurations to establish satellite networking cliques and clusters imitative of civic participation and engagement. Although these extraneous ties brought additional stocks of social capital to the networks, these were prudently secured between social peers with strategies of social closure continuing to preserve the integrity of the networks. The nature of the relationships which the ties secured are also considered with regards to a number of conceptual theories which deal with conditions of mutual trust, cooperation, reciprocity, obligations and honour. The greatest challenge to the durability of the networks occurred with the transatlantic migrations and an increase in the volume of colonial trade. From the localised immediacy and intimacy of the Highland kinships the networks adapted to conditions of distanciation so that a networking continuum was sustained thereby linking the transatlantic clusters and cliques. As it was the networking ties not only served as channels of information but as highways which facilitated and stimulated a great deal of mobility. Although these networks may well have mitigated against many of the risks inherent in colonial trade, social closure tended to inhibit access to the wider stocks of opportunity, expertise and knowledge which lay beyond the limiting parameters of what was effectively a closed market.

In the following thesis I outline Schopenhauer’s ethics in its metaphysical context and in contrast to ethics based on egoism. I look at criticisms of Schopenhauer’s philosophy which have emerged quite recently, and some of which (if valid) would undermine Schopenhauer’s compassion-based moral theory. I have explained these criticisms and offered a defence of Schopenhauer. In order to take up Schopenhauer’s claim of affinity with Buddhist philosophy, I outline first of all early Buddhist then Mahāyāna ethics focusing on the latter’s central idea of compassion. It has been suggested by some scholars that there are specific problems in Buddhist ethics which undermine the idea of compassion and I explain, then attempt to counter, these claims with specific reference to Śāntideva and his rejection of egoism as a means of acting in a moral way or of finding liberation from suffering. I then address recent criticisms of Śāntideva’s Bodhicaryāvatāra, especially the idea that the specific role of compassion in his ethics and its soteriological role are illogical – an idea which I argue against. Finally I compare the core ideas of Schopenhauer’s solution to the problem of suffering with what seems similar in Śāntideva. In doing this, I examine whether or not Schopenhauer is right in claiming convergence between Buddhism and his own philosophy, especially in the area of soteriology as it relates to ethics.

This thesis focuses on the issue of people in software maintenance and, in particular, on software immigrants – developers who are joining maintenance teams to work with large unfamiliar software systems. By means of a structured literature review this thesis identifies a lack of empirical literature in Software Maintenance in general and an even more distinct lack of papers examining the role of People in Software Maintenance. Whilst there is existing work examining what maintenance programmers do the vast majority of it is from a managerial perspective, looking at the goals of maintenance programers rather than their day-to-day activities. To help remedy this gap in the research a series of interviews with maintenance programmers were undertaken across a variety of different companies. Four key results were identified: maintainers specialise; companies do not provide adequate system training; external sources of information about the system are not guaranteed to be available; even when they are available they are not considered trustworthy. These results combine together to form a very challenging picture for software immigrants. Software immigrants are maintainers who are new to working with a system, although they are not normally new to programming. Although there is literature on software immigrants and the activities they undertake, there is no comparative literature. That is, literature that examines and compares different ways for software immigrants to learn about the system they have to maintain. Furthermore, a common feature of software immigrants learning patterns is the existence and use of mentors to impart system knowledge. However, as the interviews show, often mentors are not available which makes examining alternative ways of building a software immigrants level-of-understanding about the system they must maintain all the more important. As a result the final piece of work in this thesis is the design, running and results of a controlled laboratory experiment comparing different, work based, approaches to developing a level-of-understanding about a system. Two approaches were compared, one where subjects actively worked and altered the code while a second group took a passive ‘hands-off’ approach. The end result showed no difference in the level-of-understanding gained between the subjects who performed the active task and those that performed the passive task. This means that there is no benefit to taking a hands-off approach to building a level-of-understanding about new code in the hostile environment identified from the literature and interviews and software immigrants should start working with the code, fulfilling maintenance requests as soon as possible.

Over the past two decades much research has examined the psychological mechanisms involved in persecutory delusions, leading to the development of competing psychological models (Freeman et aI., 2002; Bentall et aI., 2001). Mills, Gilbert, Bellew and McEwan et aI., (2007) suggest an additional perspective on paranoia can be gained by exploring the way human capacities for dealing with threats have evolved. They note paranoid individuals have a heightened sensitivity to threats from others, and when threat is detected this provokes a defence of anger and aggression. Furthermore, and of relevance to the present study, they propose this angry and aggressive way of relating to others can be internalised, leading to emotional distress. Consistent with this theory, they found that students with paranoid beliefs tended to engage in heightened self-attacking of a 'hateful' nature, which seemed to have a 'self-persecutory' function. Using a cross-sectional design and questionnaire methodology the primary objective of the current study is to ascertain whether people with persecutory delusions engage in self-attacking of a hateful and persecutory nature in comparison to people with depression and in comparison to healthy controls. This study also seeks to collate exploratory data enabling the development of hypotheses about the links between self-attacking and (l) emotional distress, (2) an individual's perception of why others may attack them and how this relates to their own self-attacks; (3) perceived deservedness of persecution (Melo, Taylor, & BentalI, in press; Trower & Chadwick, 1995) and (4) recovery style (Drayton, Birchwood, & Trower, 1998). The results suggest that people with persecutory delusions engage in more selfattacking of a persecutory nature than healthy control subjects, less self-reassurance but also less self-corrective self-criticism. Exploratory data is presented suggesting the forms and functions of self-attacking and self-criticism are associated the perceived forms and functions of others-attacking, that hateful self-attacking and selfcriticism are strongly associated with emotional distress in this group, and that treating oneself as inadequate is associated with perceived deservedness of persecution. The results are discussed within the context of the current theoretical understanding of persecutory delusions and in the context of the methodological limitations the current study. Recommendations for future research and the possible clinical implications of the findings are also discussed.

Pullulan has been chemically modified by the incorporation of various hydrophobic molecules, to produce two types of derivatives (hydrophobically modified carboxymethyl pullulans (HMCMPs), and crosslinked carboxymethyl pullulan). The foregoing modifications were performed in two steps from the parent pullulan. The first step involved carboxylation of pullulan with sodium chloroacetate yielding carboxymethyl pullulan (CMP). The second step involved the medication of CMP by coupling different amine functionalized molecules onto the carboxylic groups of CMP, using the coupling agent dicyclohexylcarbodiimide. The amines used in this modification step were: hexadecylamine, decylamine, cadaverine (1-5 diaminopentane), and three jeffamine® (polyoxypropylenediamine) compounds of differing molecular weights (230, 400 and 2000). Results concluded that all six pullulan derivatives show an increase in reduced viscosity to varying degrees, compared to the parent pullulan. Characterization of pullulan and the derivatives concluded that the correct structures have been synthesised. Gel permeation chromatography confirmed that four pullulan derivatives had been crosslinked (due to doubled molecular weight terms), and a further two have increased in molecular weights, with no increase in polydispersity indices. Isothermal titration calorimetry experiments were initially performed on model systems (two different ß-cyclodextrins, and benzoic acid and eletriptan hydrobromide), and then on pullulan and the derivatives with eletriptan hydrobromide. These experiments probed the nature and extent of drug binding interactions. Results concluded that pullulan derivatives showed exothermic drug binding interactions with the named drug, with the exception of jeffamine 2000 crosslinked CMP, which exhibited endothermic interactions with the titrated drug. Pullulans excellent film forming capabilities may lead these polymers to a novel oral dosage form containing active (dissolving films).

A review ofthe literature revealed that norsearch to date has focused on women's recovery from post-natal trauma. The aim ofthe current study was to explore the 'lived experience ofrecovery' (Deegan, 1988) using a qualitative approach. A purposive sample ofeleven participants who felt that they had made a partial or fuII recovery after being traumatised by childbirth completed written accounts oftheir recovery. Retrospective assessment ofwomen's PTSD symptoms when they were at their worst indicated that fIve women had met fuII criteria for PTSD according to a checklist based on the Post-traumatic Distress Scale (Foa, 1995), and all nine participants who returned the checklist could be considered as 'partial PTSD'. Analysis ofrecovery stories produced four main themes. Women's recovery was aided by the provision ofvalidation and support and a healing birth experience. Recovery was hindered by items that kept them living the trauma and feelings ofloss. Despite making a partial recovery, some women could not progress further as they continued to feel an intense sense ofloss at not having had their desired 'good' birth experience. This had implications for their mood, behaviour and perception ofthemselves as mothers.

Studies performed on the multi-domain cell cycle regulatory protein Cdk2 showed that the protein unfolds in a 3-state manner. The intermediate converts to the native state on a very slow timescale. Mutation analysis shows that the protein can accommodate mutations at lower energetic cost than small single domain proteins, presumably by rearrangement of the structure. Kinetic studies show that the β-sheet N-terminal lobe unfolds rapidly followed by the slower unfolding of the α-helical C-lobe. Analysis of the refolding kinetics was hampered by the presence of a cis praline in the structure. However, mutation of this praline to alanine enabled a fast refolding phase to be detected. The 226 residue protein gankyrin is composed of seven ankyrin repeats that stack linearly to form an elongated, predominately α-helical structure. The protein unfolds in a reversible and two-state manner at equilibrium with a free energy of unfolding in water of 10.8 kcal mol-1. The chevron plot is described by at least four different regimes, giving rise to different types of non-linearity. At the very lowest denaturant concentrations the rate constant increases with increasing denaturant concentrations, suggestive of an off-pathway intermediate. At slightly higher denaturant concentrations there is rollover in the refolding limb, indicating the formation of another folding intermediate. In the early part of the unfolding limb of the chevron plot, upward curvature is observed, rationalised as parallel pathways. In the later part of the unfolding limb, downward curvature is observed and this behaviour was fitted according to a sequential transition states model. The order of structure formation in the folding of gankyrin was probed using protein engineering techniques.

Argulus spp. are branchiuran crustaceans, the majority of which are ectoparasites of fish. In the UK three freshwater species have been recorded: A. foliaceus, A. japonicus and A. coregoni. Argulus spp. have been reported to cause mortality in stillwater trout fisheries, but little data is currently available as to the problems they cause or ways to control them. This study was carried out within the broad aims of the sponsors, which were as follows: a) To review of the current perception of the extent and severity of Argulus spp. infections in UK Stillwater trout fisheries, and identification of the methods currently employed for controlling these infections. b) To review and increase the knowledge of the biology and ecology of Arglilus spp. in relation to these systems. c) To assess the prospects for novel control and management strategies to reduce economic loss. A cross-sectional, questionnaire-based study of 69 randomly selected stillwater trout fisheries showed that Arglilus spp. infections may cause economic loss, through a reduction in the number of anglers attending a fishery. Argulus spp. are perceived to reduce the feeding and therefore catchability of trout. This, in combination with the resulting reduction in condition and aesthetic appeal of fish is believed to reduce angler numbers. In year 2000, 29% of stillwater trout fisheries in the UK suffered a problem infection. Argulus spp. were widely distributed throughout the UK, although problem infections appeared more common in central and southern England and Wales. A. foliaceus was the most common species being found in all but one of the infected study waters. The cross-sectional study identified three factors associated with problem Argulus spp. infections. Presence of an algal bloom/ high turbidity, and slow stock turnovers were both associated with an increased risk ofa problem infections, and a drop in water level was associated with a reduced risk of a problem infection. A longitudinal study of the population ecology of A. foliaceus in five trout fisheries of varying management intensity was conducted to identify correlations between risk factors and increase our knowledge of the population dynamics of A. foliaceus. The study also investigated the effects of temperature and identified key points in the life-cycle of Argulus spp. around which interventions could be targeted. Low water clarity and high temperatures were significantly correlated with a high abundance of A. foliaceus. Low water clarity was also associated with reduced stock turnover and would suggest that high numbers of A. foliaceus alone may not affect the catch. The abundance of A. foliacells is greatest towards the end of summer and drops to low levels over winter. The first and second cohorts of the season hatch, in May and June respectively, from eggs that have over-wintered. These cohorts became adult and stal1ed laying eggs in July and August. The over-wintering of hatched stages of A .. J()!iaceus is dependent on a slow winter stock turnover of fish and the presence of reservoir hosts. If these stages over-winter they lay eggs at the end of April that hatch in July. A cohort then hatches every month until September, giving a total of 5 cohorts hatching in a year. The cohorts hatching in July and August lay eggs that over-winter, and the September cohort over-winters as hatched stages. Field studies also elucidated valuable information on the egg laying habits of A. foliacell.\', determining that egg laying occurred between April and September, before stopping over the winter month. Depth of egg laying was found to increase as the season progressed, and was found to occur deeper in clear water than turbid water. Laboratory experiments were used to study the effects of illuminated & darkened conditions, different host species and temperature on the infection success and survival of the parasite. Infection success was high under all conditions. Subsequent survival was similar in all of the experiments, but the likelihood of the parasite reaching adult size was greatest at temperatures of 20°C. Experiments also showed that the metanauplii of A. foliaceus could not survive without a host for more than 3 days. This project has successfully identified the problem posed by Argulus spp. infections to UK stillwater trout fisheries and determined the extent and severity of such problem infections. Several risk factors associated with problem infections were identified and studies were carried out in relation to the parasites population ecology. This work has greatly increased our understanding of the factors controlling A. foliaceus populations, and has led to the development of a series of management recommendations and opened avenues for further research.

This thesis describes and evaluates Dense Surface Models (DSMs), a new technique for building point distribution models of surfaces, from raw input data. DSMs can be used on data from a wide range of surface acquisition systems without preprocessing since they do not require that the surfaces be closed or even locally manifold, and can cope well with holes and spikes in the surfaces. This is an advantage over comparable techniques, which impose such constraints on the input. The core of the DSM algorithm is as follows. A dense correspondence is made between the surfaces using thin-plate spline warping guided by means of a small set of hand-placed landmarks. The area of interest is automatically defined by a threshold on a measure of the closeness of the correspondence at each point. A point distribution model is then built using the vertices from the trimmed and densely-corresponded surfaces. The key benefit of using models of the whole surface is illustrated by the large improvement in classification on face shape that is obtained when using DSMs as compared to landmark-based geometric morphometrics. This is demonstrated by testing classification by gender and also by congenital anomaly where facial growth and form is abnormal. The latter is currently the primary application of DSMs. The use of DSMs for automatically fitting to new scans is evaluated for robustness and accuracy. Methods for analyzing continuous and discrete parameters such as age and gender are presented and evaluated. The incorporation of grey-level information with the shape information is also possible, and is explored.

This thesis traces the efforts of successive Governments of both persuasions to reform the ancient jurisdiction of the spiritual courts over the validity of wills of personal property. Those non-partisan efforts spanned three decades and resulted in the 1857 Court of Probate Act. A Royal Commission, reporting in 1832, recommended in effect that the jurisdiction be centralised in London by transferring it from the Province of York and from the diocesan and inferior courts to the Prerogative Court of Canterbury at Doctors' Commons, where the specialist civilian lawyers practised their separate and monopolistic body of law. Because the Real Property Commission preferred a secular solution, the 1832 Report was endorsed by a Commons Select Committee in 1833 and modified by a Lords Select Committee in 1836 to allow a limited non contentious local jurisdiction. Several early attempts to bring in reforming measures based upon the centralising 1832 Report failed because of local opposition, a lack of resolve on the part of Ministers and the pressure of other business. Two Government Bills were introduced during Peel's Second Ministry. The 1843 Bill failed because it pursued a centralising policy. The 1844 Bill failed because it departed from that policy and offered to keep the diocesan courts. The Whig Opposition introduced its own centralising Bill in 1845 but it too failed. After the inactivity of Russell's administration, efforts at reform were resumed in the 1850s by rapidly changing Governments, but were hampered by local opposition, pressure of other business, and the Crimean War. By then the 1854 Report of the Chancery Commission had recommended that the entire jurisdiction should be removed to a secular court, and the debate raged about which practitioners should benefit. Finally, after pressures in the Commons to secure appropriate compensation and district probate offices with extended powers, the 1857 Act ushered in the present system.