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Around half of all type 1 diabetes cases occur in adults but the phenotype of the disease in this age group is poorly understood. A major difficulty studying type 1 diabetes in adults is differentiating cases from type 2 diabetes. The aim of this thesis was to both determine strategies for improving type 1 diabetes classification in adults and evaluate the impact of onset age on clinical phenotype in robustly defined adult-onset type 1 diabetes. Chapter 1 explores the reported characteristics of adult-onset type 1 diabetes and how this varies with case definition. I discuss difficulties classifying adult-onset type 1 diabetes and how this might impact the observed phenotype. Chapter 2 evaluated the commonly reported reduction in positive islet autoantibodies with increasing onset age in type 1 diabetes. We show a significant reduction in genetic predisposition to type 1 diabetes in autoantibody negative adults concluding that most of these cases probably have non-autoimmune diabetes. Chapter 3 examines in adults diagnosed with type 1 diabetes the clinical benefit of measuring and reporting autoantibody results to patients and their clinicians given in Chapter 2 a high proportion without autoantibodies likley have non-autoimmune diabetes. This showed some autoantibody negative cases stopping insulin without detrimental impact on glycaemic control. Chapter 4 explores the conflicted evidence for the loss of HLA (DR15-DQ6) associated protection against type 1 diabetes with increasing onset age. We show that in adults when type 1 diabetes is defined robustly, protection remains. Chapter 5 further builds on the importance of robustly classifying type 1 diabetes in adults. We show that presentation and progression of type 1 diabetes in adults is equivalently severe irrespective of onset age. Chapter 6 evaluated commonly used approaches for defining diabetes type in datasets where biomarkers for diabetes classification are unavailable. This identified the optimum approach to be BMI and Age of diagnosis used continually within a prediction model. We produced an online tool allowing researchers to select the optimum approach for their research question. An overview of the major finding of each chapter, their implications and potential future research are discussed in Chapter 7.

Pollinators are essential to food security but are under threat because of multiple factors including climate change, habitat loss, emerging infectious diseases and pesticide use. Commercial pollinator provision can support threatened pollination services, however, only a few species are currently available. This study assessed the viability of mass-rearing red mason bees (Osmia bicornis) within a lab and greenhouse setting, as well as methods to manipulate the diapausing stage, and thus extend when this species is available to growers. Reproductive rates were too low to be commercially viable, but diapause was successfully extended using fluctuating thermal regimes and could be terminated early using chemical treatment. Climate change was shown to potentially have significant effects on red mason bees, with spring warming likely to advance adult emergence, and delayed winter cooling decreasing survival. Neonicotinoid pesticides impact was then assessed in three species: red mason bees, pollinating flies (Calliphora vicina) and buff-tailed bumblebees (Bombus terrestris). Sub-lethal, field-relevant, doses had a significant impact on thermal activity thresholds of all species, with buff-tailed bumblebees the most vulnerable. Indeed, RNAseq data in this species highlighted disruption of several core processes linked to thermal adaptation. The implications on pollinator phenology, survival, as well as food security are discussed.

This is a portfolio of mixed compositions for a range of musical media. Composition as research is the main theme running throughout the portfolio. Particular focus is given to experimental aspects of composition, in order to see how these function as both creative tools and modes of communication. For example, use of sampling, use of code followed by digital manipulation, conventional notation and unconventional instruments. Some of the compositions are written specifically for performance, one is written specifically as sound design for a film, and others stand as experimental electronic works.

Over-expression of indolamine-2,3-dioxygenase 1 (IDO1) and programmed death-ligand 1 (PD-L1) are common phenotypes of immunoresistant cancers. The expression of IDO1 and PD-L1 is mediated by the janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway in response to stimulation by interferon-gamma (IFN gamma), with tumoral signalling specifically transduced via JAK2. IDO1's role in tumour immunoresistance is mediated by both depletion of its substrate, L-tryptophan, and by metabolites derived from its product, N-formyl-L-kynurenine. The mechanism of IDO1-mediated dioxygenation of L-tryptophan to N-formyl-L-kynurenine proceeds by either a radical or electrophilic-based mechanism. Radicals adjacent to cyclopropane rings undergo ring-opening driven by relief of ring strain, with the rate of ring-opening dependent on the stability of the resulting radical. A series of cyclopropane-containing IDO1 substrate mimics were designed to divert the hypothesised radical dioxygenation mechanism, potentially resulting in enzyme inhibition resulting from either a mechanistic 'dead-end' or covalent inactivation of the protein. Based on tryptophan and tryptamine, 1,2-cyclopropanated analogues were synthesised via a 1,3-dipolar cycloaddition of an amino acrylate and a indolo-diazo species or the Rh-catalysed cyclopropanation of a terminal olefin. Complimentary spirocyclic cyclopropane analogues of tryptophan and tryptamine were accessed via cyclodialkylation of 3-indoleacetonitrile. A library of sulfenylindoles was also synthesised to divert late-stage metabolic intermediates in a non-radical dependent manner. The synthesised inhibitors were exposed to IFN gamma-stimulated SCOV-3 cells and demonstrated a broadly poor ability to inhibit IDO1 turnover of tryptophan. Novel cell-free assays were developed to ascertain whether the reduced reactivity was related to compound cell-permeability and to further probe the mechanistic-detail of IDO1. A promising IDO1 inhibitor was identified in the cell-free assays and the further evaluation of the candidate is described. Study of JAK2's role in tumour immune escape has been complicated by inhibitors direct effects on immune cells, which is thought to be mediated by inhibition of other JAK family members. Proteolysis targeting chimeras (PROTACs) have the ability to degrade proteins within cells by harnessing the ubiquitin-proteasomal system. Based on FDA-approved JAK2 ligand fedratinib, a series of PROTACs were synthesised. The synthesised PROTACs were evaluated in JAK2-expressing HeLa cells. Degradation of JAK2 in HeLa cells was not observed in the preliminary western-blot analysis - future investigations of JAK2 PROTACs is discussed.

This thesis contributes new evidence and analyses on the effects of cash transfers on adolescent school attendance, work participation and marital status. The mixed-methods study investigates the effects of Nepal's Old Age Allowance (OAA), an unconditional cash transfer, on adolescents who co-reside with older persons using primary data from a household survey (n=2018) and in-depth interviews (IDI) (n=55) conducted in Rautahat district in the Terai region. The quantitative analysis exploits the age criteria for OAA eligibility to isolate its effects on co-resident adolescents. Using a hybrid thematic approach, IDIs are used to elucidate whether and how the OAA was factored into household decision-making and its relation to other factors that influence decisions about adolescents' lives. The findings show that the OAA supports households to fulfil existing preferences for adolescents, which depend on the socioeconomic status, decision-making dynamics and religion of the household, the type and quality of local schools, the nature of local credit markets, and gendered social norms and expectations attached to transitions to adulthood. For many adolescents, this means increased access to school, whether public, private, or religious. However, some households support adolescents to access private school by taking loans in anticipation of OAA eligibility but fail to sustain the costs in the face of delays in registration and receipt of the first payments. Some out-of-school adolescents are prevented from engaging in paid work. However, other households use the OAA to accelerate transitions to adulthood, supporting economic migration of older boys and expediting the formalisation of marriage of older girls. This study makes five main contributions to the literature. First, studies on income effects on access to education tend to consider school as a homogenous entity, but the findings show that a UCT can expand school choice with different effects for different types of school. Second, the findings on adolescent marriage are novel for a dowry context and should prompt the research and policy literature to recognise the possibility that UCTs can increase the risk of early marriage. Third, this study provides unique evidence on the role of cash transfers in leveraging loans for human capital investment and marriage. Fourth, the study examines the dynamics of household decision-making in relation to causal processes and shows that variation in outcomes according to the gender of the cash transfer recipient may stem from differences in bargaining power and economic opportunity as much as from differences in preferences. Finally, most studies on cash transfers often fail to account for the complexity in people's lives which may lead to blunt or erroneous conclusions. This study shows that adopting the tenets of a critical realist perspective and placing decision-making about the outcomes of interest at the centre of the analysis focuses attention on the diverse contextual factors that shape the effects of cash transfers on individual household members, and provides for richer and more nuanced findings.

This portfolio provides an insight into the development of a trainee sport psychology practitioner’s journey through the Professional Doctorate in Sport and Exercise Psychology at Liverpool John Moores University. The portfolio provides evidence, through a combination of consultancy, research, and reflective practice, of how the trainee sport psychology practitioner successfully meets the competencies (professional standards, consultancy, research, and dissemination) of the British Psychological Society’s (BPS) Stage Two training pathway. The three applied case studies and one applied teaching case study provide a critical and reflective insight into the work conducted with elite athletes and coaches from a variety of sports. These applied consultancy experiences allowed the trainee practitioner to develop a coherent and congruent philosophy of practice, which can now be confidently delivered across contexts and cultures. Throughout these applied experiences, the trainee practitioner was able to demonstrate diversity in their training by working with multiple sports (gymnastics, triathlon, wrestling, rugby-league, football, and golf). The reflective log highlights the critical moments experienced by the author throughout this journey, which support the development of a coherent personal and professional identity. The two empirical papers and systematic review attempt to bridge the gap between theory and practice by exploring topics such as; use of psychology within the coaching context, importance of reflective practice for optimal practitioner development, and the impact critical moments have on the practitioner individuation journey of applied sport psychology practitioners. The research, combined with the opportunities to disseminate at conferences and as a Lecturer of Sport Psychology, allowed the author to understand how his values and beliefs transferred across his consultancy, teaching, and research.

This thesis reassesses the evidence surrounding Edward Irving’s controversial teaching about the doctrine of the incarnation. Irving was a controversial figure in his own day and his legacy has been contested ever since he was dismissed from the ministry of the Church of Scotland for teaching that Christ had a ‘fallen’ human nature. This thesis re-examines the emergence and significance of Irving’s teaching. It evaluates the scholarly consensus that his distinctive Christology was a stable feature of his thought and argues the case that his thinking in this area did change significantly. Methodologically, this thesis draws on some aspects of Quentin Skinner’s work in the importance of context (Chapter Two) to understand Irving as he really was, rather than in terms of his later significance. In the light of this, Irving’s biography is examined in Chapter Three, before moving into a discussion of the influential part played by Samuel Taylor Coleridge in Irving’s intellectual development (Chapter Four). The second half of the thesis then moves on to consider the development of Irving’s Christology and the questions surrounding its provenance and development (Chapters Five and Six). Finally, in Chapter Seven, possible sources of explanation for Irving’s distinctive ideas about the Incarnation are exhibited and assessed. The argument of this thesis is that Edward Irving developed an account of the Incarnation that was essentially novel, in response to the Romantic ideas that he had derived from Coleridge. In accordance with Coleridge’s assessment, it is argued that this derivation was rendered more complex by Irving’s incomplete apprehension of Coleridge’s underlying philosophy. Nonetheless, it is argued that Edward Irving’s teaching presented a Romantic version of Christ, and that this distinctive conception owes more to the times in which Irving lived than to the theological tradition to which he claimed adherence.

Nutrient sensing neurons are unique in coupling changes in the concentration of nutrients to changes in neuronal activity. These neurons typically exist in regions of the brain where the blood brain barrier is fenestrated, such as the arcuate nucleus of the hypothalamus. Glucose and leucine are nutrients known to be sensed by neurons in this brain region, but the mechanisms by which they are sensed, and cells that sense them require further study. Using calcium imaging of adult neuron cultures from the mouse mediobasal hypothalamus, I demonstrated that leucine bidirectionally regulates neuronal activity in a neurochemically heterogeneous population of neurons, including AgRP/NPY and POMC neurons. Using pharmacological tools, I demonstrated, unexpectedly, that this acute sensing is independent of mTOR and leucine metabolism, known pathways involved in leucine sensing in vivo. Leucine sensing is LAT1 independent. The response principally relies on calcium entry into the cell across the plasma membrane, but IP3 sensitive calcium stores play a role in neurons inhibited by leucine. Using phosphoTRAP and single cell RNA sequencing, I aimed to identify a molecular marker for leucine sensing cells to allow their manipulation in vivo. PhosphoTRAP, and subsequent pharmacological studies identified a T Type calcium channel may be a marker for leucine sensing cells. AgRP neurons are essential for feeding, and also play roles in controlling glucose homeostasis. Using chemogenetics to selectively activate these neurons, I demonstrated, in contrast to a similar, recently published study, that blood glucose concentrations did not rise upon activation of these neurons. A subpopulation of AgRP neurons express glucokinase, and some AgRP neurons are glucose inhibited, but the role of glucokinase in these neurons has not been characterised. Our lab generated an AgRP neuron specific glucokinase knock out mouse line. Preliminary results suggest 18 – 25 week old female AgRP glucokinase knock out mice may have altered glucose tolerance, but conclusions can only be drawn once further mice have been phenotyped, and the success of the glucokinase knock out from AgRP neurons has been confirmed.

Adsorption isotherms in chromatography are critical in determining the separation of solutes during column separations. Multicomponent protein adsorption isotherms, which are relevant during the downstream processing of biopharmaceutical products, have received limited study historically. The studies and methodologies which have been assessed have mainly focused on small, simple, chromophore containing proteins which have limited applicability to industrially relevant bio-therapeutics. The reasons why this area of study has received limited attention include the experimental effort associated with generating such large data sets as well as the difficulty in obtaining data of good enough quality. The work explored here presents and optimises the deployment of highthroughput chromatography formats as well as automated liquid handling systems in order to elucidate adsorption isotherms of proteins. Additionally, alternative rapid analytical methods involving the collection of protein UV spectra in conjunction with multivariate data analysis have been applied to quantify protein mixtures. These rapid high-throughput methods decrease the experimental effort associated with multicomponent isotherm studies. 3 binary isotherms and 1 ternary isotherm have been studied for larger, non-chromophore containing model proteins. The propagation of error in single component and multicomponent isotherms has been investigated to understand what drives the propensity for error as well as methods to mitigate problematic regions of investigation. The fitting of the multicomponent ion exchange isotherms across multiple salt levels to isotherm formalisms proved elusive which precluded their application for in silico modelling of column separation. Short of that a heuristic optimisation of a binary mixture was achieved quantifying eluted fractions using the UV spectra multivariate method.

Introduction: Low rectal cancer management presents a unique challenge. On one hand more radical measures are required to address poor oncological outcomes and on the other hand there is a need to avoid unacceptably high permanent colostomy rates and suboptimal post-treatment function. This thesis investigates radiological, surgical, pathological and quality of life factors in low rectal cancer, in order to predict outcomes and provide a patient-tailored approach to low rectal cancer management. Methods: The majority of data presented within this thesis will be from the ongoing Low Rectal Cancer Study (MERCURY II). This multidisciplinary study prospectively collected surgical, radiological, pathological and QoL data in consecutive patients undergoing treatment for low rectal cancer. In addition, a multicentre crosssectional quality of life study was performed. This was designed to evaluate post-operative bowel function using patient reported outcome measures (PROMs). Results: Analysis from 279 low rectal cancer patients from the MERCURY II study suggested that MRI assessment of the low rectal plane (mrLRP) guided selection for pre-operative therapy and for restorative resection. MRI assessment contributed to the low (9%, 25/279) pathological circumferential resection margin (pCRM) involvement; significantly lower than the pre-stated target of ≤15% and lower than published studies. Multivariate analysis identified three other predictors for pCRM involvement: tumour ≤4cm from the anal verge; anterior quadrant tumour invasion; and MRI evidence of EMVI. This thesis also validates the English translation of a Danish PROM (LARS score). This data was also used to predict for post-operative bowel-related quality of life (BQoL) impairment following a restorative anterior resection. Finally, the UK LARS data was used to develop a model that predicts post-operative bowel dysfunction (POLARS) with external validation with Danish data. Future Work: The predictors for pCRM involvement require external validation. Future studies should also explore the relationship between these predictors and long-term survival. The POLARS and the LARS score should be used in clinical practice to identify patients who may benefit from additional support for postoperative bowel dysfunction. The value of the post-treatment MRI requires further investigation and the TRIGGER trial has been designed for this purpose.

Special guardianship is a new but rapidly expanding area of permanency planning that is increasingly popular with families and kinship carers. In 2017, 3,690 children left care for a special guardianship placement, and a further unknown number were granted orders in private proceedings. An integral feature of this new legal option is that where it is considered to be in the child's best interests, they should continue to have some level of contact with their parents, after the special guardianship order has been granted. Social workers have a duty to assess, plan and recommend what the nature of that contact should be. However there is virtually no policy guidance provided to them on how to undertake those duties. Positive contact with their birth parents can help a child maintain existing bonds, while making sense of how they are part of two families, in order to explore and develop their sense of personal identity. To a large extent it will also determine the nature and success of the child's future relationship with their parents. So these are vital decisions that will affect the child's physical, psychological and emotional wellbeing. Yet very little is known about the process that social workers undertake in order to decide what level and type of contact is appropriate in each special guardianship case. This study set out to investigate the planning and recommending of birth parent contact in special guardianship cases. The literature review demonstrated a paucity of studies of this field to inform policy and practice, although information was gathered from other fields where contact is held, such as kinship care and fostering. The research method comprised of an online questionnaire that was completed by 102 local authority social workers, two focus groups for social workers and two focus groups for special guardians. The results provided quantitative data on what social workers included in their recommendations, and the factors they considered in reaching their decisions. Qualitative data from practitioners described the difficulties in planning contact for the long-term in complex and fluid family contexts. Involving special guardians in the study gave a chance to include the different perspectives of the people who have to make the contact recommendations work, and contrast their views on contact planning with those of the professionals. The carers provided additional insights into the challenge of managing contact, and the problems they faced when the parents were not always reliable or responsible. Recommendations for addressing the issues raised included more use of reviews of contact, a scheduled move from the initial contact plan to the special guardian assuming full responsibility for contact decisions, keeping cases open for a 'settling in' period, proposals for all contact plans to include training, and a rebalancing of the responsibility for contact onto parents through the use of contact agreements. This study has provided understanding of a crucial area of child permanency planning that has not been investigated before, by including the large-scale involvement of social workers, and introducing the contributions of service-users.

This thesis revolves around the idea of ‘great work’; work that is meaningful, enjoyable, and highly productive in the broadest sense. While the commonly held belief is that very few people are lucky enough to have such jobs, it turns out that great work is not something magical, which happens by chance, but actually something which can be cultivated. Several common psychological and social (psychosocial) factors including the ability to influence decisions which affect yourself at work, and whether you feel adequately rewarded (including non-financial rewards) have been identified as key contributors. As work is something that most people around the world do for most of their lives, the implications of whether work is great or much less are sizeable and could be viewed from many perspectives. Chapter One reviews these ideas. It culminates in the presentation of the Psychosocial Risk Management Excellence Framework (PRIMA-EF) which highlights the link between psychosocial factors and several outcomes. The thesis adopts this framework as its theoretical backing. In Chapter Two, this thesis breaks down the outcomes associated with the working environment, as envisioned in PRIMA-EF, into individual, organizational and societal, drawing on different aspects of the literature. Individual outcomes can be split into individual psychological states (such as health, engagement, and creativity), and work outputs (including productivity and quality of that productivity). At an organizational level, what happens to individual employees influences the group as a whole, for example productivity and innovation may be affected thus impacting upon overall performance of the organization. At a societal level, once again, smaller units of individuals and organizations can be thought of as having a macro level effect. For example, unhealthy modes of working will ultimately affect public health. Chapter Three moves on to the question of how organizations can be further motivated to better manage psychosocial factors. In particular, organizational change theory has identified political, competitive, and social categories of drivers that are relevant. Chapter Three reviews the evidence of whether more is required from organizations and what specific pressures could arise from these three categories. Following this review of the existing literature and status quo, Chapter Four describes the philosophical position underlying the subsequent research. It goes on to establish the operational aspects of the methodology and methods selected for the subsequent studies, providing details on the sources of data used and the analyses conducted. The first two studies explore some of the aforementioned relationships between psychosocial factors and outcomes as existing research on these associations could be added to. Outcomes considered include, work engagement, innovation, quality, productivity, and financial performance. The overarching conclusion from these investigations is that the psychosocial work environment is associated with a number of important outcomes, much more broadly than traditionally thought. Given this importance, the third and final study of the thesis considers how to drive organizations into improved management of the psychosocial work environment. Political, competitiveness and social drivers are considered with results emerging that were somewhat contrary to expectations. In particular, social drivers emerged as the strongest reason for organizations implementing interventions to manage the psychosocial work environment. The final chapter discusses the insights and contributions emerging from this thesis whilst also picking up on some important considerations regarding the psychosocial work environment, and directions for moving work carried out in this area forward.

The ability to inexpensively and reliably detect organic compounds is important across a multitude of different areas of science. Benzene ring functional groups are found in a wide variety of biological molecules, (such as amino acids, DNA nucleotide bases and blood based components). The qualification and quantification of these compounds in a sample has been achieved by techniques such as high performance liquid chromatography (HPLC), gas chromatography (GC), mass spectrometry (MS) and nuclear magnetic resonance (NMR), amongst others. These techniques, however, often require cumbersome, expensive equipment along with exhaustive sample preparation techniques and are thus not necessarily suitable for portable in-situ analysis of these compounds. This thesis details the fabrication and characterisation of graphene modified electrodes that show an increased sensitivity towards biomolecular compounds such as dopamine, amino acids, and DNA. The graphene was synthesised using a novel semi-automated method which was performed using a bespoke apparatus designed to alleviate the labour involved in synthesising graphene by the sonochemical method. The method involved pumping an aqueous solution of the surfactant into a solution of graphite in water which was under constant sonication. When used in an electrochemical system employing cyclic voltammetry the graphene modified electrodes showed not only a lower limit of detection in all cases, but also a shift in peak position which allowed for simultaneous quantification of mixtures of compounds. This could not be achieved with screen printed carbon electrodes alone as different peaks often occur at similar potentials, making it difficult or impossible to quantify these compounds individually. Slower scan rates can often give rise to separate peaks, however this adds time to the experiment which is not necessary with graphene modification. The binding interactions of novel resorcinarene molecules were also predicted by molecular modelling techniques and then confirmed using NMR binding experiments. The resorcinarene was tested against a range of different analytes and showed a degree of specificity. The interaction between the two surfactant molecules and the graphene surface was also analysed to determine whether or not the resorcinarene molecules could be adsorbed onto graphene to produce a viable, molecularly specific electrode surface.

This thesis undertakes a study of human addictions, particularly drug and alcohol dependency, from the disciplines of psychology and theology, working towards an integrated study. In the first instance it sets out to understand the aetiology of addictive behaviour, as an important stage in the process of helping addicted people to overcome their substance dependency. Secondly, it aims to provide a well-researched and robust framework for the pastoral care of people who are addicted as part of the Christian Churches’ response to serious social problems both for individuals and families. It is argued that confusion about the aetiology of addiction, and how best to treat addicted people, contributes to the failure of many treatment modalities to provide effective long term relief. A new model for understanding addiction is proposed. This model begins in a different place: it argues that we would have a better understanding of addiction and how to treat it if we began by investigating human desires and aspirations, before attempting to understand why for some people desire for drugs becomes excessive or distorted. It is suggested in the final section of the thesis that, in line with Augustinian thought, all human longing has its roots in desire for God, even though people may not be aware that the ultimate goal of their quest is an experience of the divine. In the concluding discussion and conclusion, we suggest that this model has important contributions to make as a discrete element in the clinical care of addicts and in the area of pastoral and spiritual care whether in parishes or other institutions where pastoral care is provided. The new model is then related to existing models of pastoral care, and examples are given of how the model is currently being presented in training programmes for pastoral ministry.

Many of the habitats occupied by fish are highly dynamic, naturally demonstrating substantial abiotic fluctuations over diurnal, tidal or seasonal cycles. It is also the case that throughout their 545 million year evolutionary history, fish have existed in aquatic environments very different to those of the present day. However, the past several decades have seen unprecedented rates of environmental change, at local and global scales, arising from human activities. The two major themes of the present thesis are: 1) Respiratory responses of fish to changes in environmental oxygen and temperature in the context of exploring intra- and inter-specific trait variation and its ecological implications 2) The effects of environmental factors (oxygen, carbon dioxide, temperature and seawater chemistry) on the intestinal precipitation and excretion of calcium carbonate by marine teleosts. In the first study (chapter two) a comprehensive database of fish critical PO2 (Pcrit) data compiled from the published literature is presented. The systematic review of this literature provided the opportunity to critically examine methodologies for determining Pcrit as well as its usefulness as an indicator of hypoxia tolerance in fish. The second study (chapter three) examines whether inter- and intra-specific variation in thermal and hypoxia tolerance in two reef snapper species (Lutjanus carponotatus and Lutjanus adetii) reflects their distributions across the contrasting biophysical environments of the reef flat and reef slope surrounding Heron Island on the Great Barrier Reef. L. carponotatus was clearly the most thermally and hypoxia tolerant of the two species, demonstrating a ~3.5 °C wider thermal tolerance zone (higher CTmax, lower CTmin) and ~26% lower Pcrit than L. adetii. These results suggest that the contrasting distribution of these species between flat and slope reef zones is reflected in their physiological tolerances. However, there was no evidence of intra-species variation in tolerance between flat and slope caught L. carponotatus individuals, indicating that this species does not form physiologically distinct subpopulations between these reef zones. The third study (chapter four) experimentally quantified the effect of hypercarbia (3000 μatm) and hypoxia (50% air saturation) on gut carbonate production by the European flounder (Platichthys flesus). Both hypercarbia and hypoxia resulted in a significant increase in carbonate excretion rate (1.5-fold and 2.4-fold, respectively) and acted synergistically when combined. In the final study (chapter five), gut carbonate production was measured in the European flounder undergoing conditions simulating the ‘calcite seas’ of the Cretaceous. The results of this study support the hypothesis that ocean conditions prevalent during the Cretaceous period resulted in piscine carbonate production rates substantially higher (~14-fold) than the present day. Ultimately, this thesis directly links the environmental physiology of fish at the individual level to wider scale implications (past, present and future), ranging from local ecological patterns all the way up to global carbon cycles.

Warm dense matter is an area of the phase diagram between solids and classical plasmas, but poorly described by theoretical descriptions of both. Collective oscillations and quantum effects all play significant roles in its structural behaviour and equations of state. Aside from its complexity, work on this state is significant as a stepping stone towards achieving energetically viable nuclear fusion, as well as representing a laboratory analogue for planetary cores and other astrophysical phenomena. X-ray scattering, using beams from X-ray free electron lasers, is used to probe the structure of samples in this state, and is shown to compare well to theoretical descriptions. Angle-resolved scattering showed sharper than expected peaks, suggesting stronger interparticle correlation than expected. Using the beam in self-seeded mode, scattering from ion acoustic waves in warm dense matter was observed for the first time, confirming theoretical descriptions of the phenomena but raising further questions due to an elastic peak in the spectra. Similar experiments in the future will allow models of ionic behaviour to be tested directly, and potentially determine the source of this feature. X-ray diffraction was used to study the evolution of samples heated by proton, electron or photon irradiation, with the aim of resolving the temperature evolution of the species within the sample. The results suggest that, although the behaviour in metallic samples is well described by lowtemperature approximations, that of graphite is more complex and does not agree with the models available.

The study was an investigation into the teaching decisions that mathematics teachers make over time. I view a mathematics classroom as a didactical system of teacher, learners and content within an educational institution, where content is the material that brings teachers and learners together. Within such a system I view the teacher's role as making content available to learners. Prior research has often investigated the teacher's role by comparing teaching practices nationally or internationally, but these comparisons have tended to use the lesson as the unit of analysis. I propose that how teachers make content available can change over the course of a series of lessons and so my study used the lesson series as the unit of analysis. I purposefully designed the study so that it involved four cases, which allowed me to explore the role of the teacher and the topic in how content was made available. To investigate how teachers made content available to learners in each case, I developed an analytical approach from which I could study the modes of teacher interaction that featured across the lesson series, the forms of mathematical content made available and the sequencing of these forms. Attending to forms of content - rather than content itself - allowed for comparison of teaching of different topics. This original analytical approach represents a contribution to both mathematics education and mixed methods research. Within this small sample of cases, quantifiable differences were identified in how content was made available between classwork and seatwork, from lesson to lesson and between cases. Between-case differences in the nature of teaching 'between-the-desks' during seatwork were also identified. These differences illuminated teaching decisions to which teachers and classroom researchers may not routinely attend. The findings therefore contribute - and identify additional lines of enquiry that might contribute further - to a more extensive understanding of teaching practices.

Maintenance of anaesthesia using the intravenous agent propofol has increased following development of pharmacokinetic models. An analyser capable of determining propofol concentrations at the point of care may lead to an improved accuracy of drug delivery. Validation work on a novel analyser measuring propofol concentration in near real time demonstrate a high level of precision for samples in the clinical range. Further work in the clinical setting was carried out using the novel propofol analyser to further research its potential use in a diverse patient cohort. Studies were performed in intensive care correlating blood propofol concentrations with depth of sedation, demonstrating a correlation with organ failure. The Marsh model of Target Controlled Anaesthesia was poorer at predicting propofol concentration in patients with significant organ dysfunction than in those without organ failure (correlation coefficient 0.36 vs. 0.73 respectively). Studies in the operating room were performed in which measured propofol concentrations were compared with those predicted using the Marsh model. Results demonstrated significant inaccuracies of the model (bias 32%, precision -8.7 to 72.6%). A method of Marsh model bias correction using a single blood propofol measurement was tested. Results demonstrated insufficient predictability to allow a single point calibration.

This practical theology thesis investigates the theology gy of the Swiss theologian Karl Barth (1886-1968)in order to see if this can help the rural parishes of the Carlisle diocese as they face the challenges set ot in the latest mission and evangelism strategy Growing Disciples Vision and Strategy: 2011-2020 (GD). The exercise brings together, in a sharp conversation, Barth and the content of GD. The dialogue leads to several practical evangelistic outcomes that are offered to the traditional churches of the diocese. The partnership that is created between Barth and Carlisle is galvanised by focusing on several concerns about discipleship expressed by both parties. These include: the nature of revelation; the possibility of knowing God; the content of the gospel; the task of minisrty and the challenge of mission and evangelism. The strategic plan expresses anxiety over declining church attendance in the Carlisle diocese. This was a matter Barth faced during his early years as a pastor and it is argued that it is an issue that should not dominate the thinking of traditional churches or deflect them from the main task of mission and evangelism. By placing the roots of Barth's thinking in the arena of Canonical Narrative Theology, the Bible becomes the main source of instruction from which creative insights are derived. However, to aviod giving the impression that Barth's theology of mission and discipleship can be transferred uncritically to Carlisle, the argument is deliberately reflective as it weaves in and out of both Barth's theology and Carlisle's strategic mission plan. An attempt is made to construct practical outcomes in the form of resources which can be offered to the rural parishes of the diocese where there is eagerness to make new dosciples.

Background. Spastic cerebral palsy is a common cause of childhood activity limitation that restricts children’s personal development. Botulinum toxin is a spasticity treatment that can improve upper limb activity limitation when combined with rehabilitation therapy. We investigated whether use of a computer-assisted arm rehabilitation (CAAR) device enhanced the benefits of botulinum toxin treatment of the upper limb of children with cerebral palsy. Method. Fifteen children with cerebral palsy aged 5 – 12 years old undergoing botulinum toxin treatment for spasticity of the upper limb were randomly allocated into a CAAR group and a control group using minimisation, a procedure that balances groups for prognostic factors e.g. age and disability. Children used CAAR at home for 6 weeks. Assessments were carried out by blinded assessor at baseline, six and twelve weeks. Primary outcome measure. ABILHAND-kids. Secondary outcome measure. Canadian Occupational Performance Measure (COPM). Results. ABILHAND-kids. Activity limitation worsened following botulinum toxin treatment. An ANCOVA revealed that this was not significant (median scores, all participants: baseline, 0.8084; six weeks, 0.145; twelve weeks, 0.334; p=0.462) and that there was no difference between groups (p=0.699). COPM. A Friedman’s ANOVA revealed a statistically significant improvement that was clinically non-significant (baseline score, 4/10; six week score, 4.6/10; twelve week score, 4.6/10; p=0.031). A Kruskal-Wallis ANOVA revealed no difference in scores between groups at each time point. CAAR use. Mean daily use, 7 minutes. Maximum use, 256 minutes (played over 24 days, mean daily use 10.667 minutes). Sample size. This sample size was underpowered by 75%. Conclusion. This study potentially supports evidence that botulinum treatment should be used only in combination with rehabilitation therapy but it was not adequately powered and a Type II error cannot be ruled out. The CAAR device did not engage the children enough to promote sufficient intensity and repetition of arm movements.

In this thesis we consider the setting where R is a complete discrete valuation ring of mixed characteristic (0, p) where p > 0 is prime. Let (p, ..., p) denote either the group Z/pZ x ... x Z/pZ or the product of rank p group schemes. Given a degree p Galois cover between R-curves, it is understood when the cover has the structure of a torsor under a finite flat group scheme of rank p. We investigate torsors under group schemes of type (p, ..., p) and establish criteria for their existence. We treat the boundary of the formal fibre and extend our knowledge of the conductor and degree of the different in degree p to the (p, p) setting. We also take the opportunity to explain how this can be naturally extended to the general (p, ..., p) case. Finally, we generalise a local vanishing cycles formula for curves known in the degree p case to Galois groups of type (p, p), relating the genus of two points in terms of just the cover's ramification data and the conductors acting at the boundaries.

This thesis presents a new bonded particle model that accurately predicts the wideranging behaviour of cementitious materials. There is an increasing use of the Discrete Element Method (DEM) to study the behaviour of cementitious materials such as concrete and rock; the chief advantage of the DEM over continuum-based techniques is that it does not predetermine where cracking and fragmentation initiate and propagate, since the system is naturally discontinuous. The DEM’s ability to produce realistic representations of cementitious materials depends largely on the implementation of an inter-particle bonded-contact model. A new bonded-contact model is proposed, based on the Timoshenko beam theory which considers axial, shear and bending behaviour of inter-particle bonds. The developed model was implemented in the commercial EDEM code, in which a thorough verification procedure was conducted. A full parametric study then considered the uni-axial loading of a concrete cylinder; the influence of the input parameters on the bulk response was used to produce a calibrated model that has been shown to be capable of producing realistic predictions of a wide range of behaviour seen in cementitious materials. The model provides useful insights into the microscopic phenomena that result in the bulk loading responses observed for cementitious materials such as concrete. The new model was used to simulate the loading of a number of deformable structural elements including beams, frames, plates and rings; the numerical results produced by the model provided a close match to theoretical solutions.

This thesis examines how the human brain adapts after peripheral vestibular injury. Vestibular perceptual function is used as a probe of cortical vestibular function. A paradigm determining vestibular perceptual thresholds to yaw axis rotation by a method of limits is described. Asymmetry in the thresholds is induced in normal subjects with galvanic vestibular stimulation. In patients with acute vestibular neuritis, perceptual thresholds were bilaterally elevated, with less asymmetry when compared to the brainstem reflexive function. Thresholds were measured in a prospective longitudinal study in vestibular neuritis patients, assessed acutely and at follow-­‐up (n=16). Assessments comprised vestibular caloric testing, visual dependency measures, questionnaire measures of symptom load, anxiety, depression and fear of body sensations. Clinical recruitment found a low rate of correct diagnoses by referring clinicians. Symptomatic outcome at follow-up was associated with increased visual dependence, asymmetric caloric function, increased anxiety and depression. It was also associated with increased fear and anxiety of body sensations present acutely, suggesting this may be predisposing. The anatomical substrate of central compensation was investigated in patients with bilateral vestibular failure (n=12) and normal controls (n=15) using functional MRI. A novel air turbine-powered vibrating device was developed to provide high and low levels of proprioceptive stimulus to neck rotator muscles. This was combined with a horizontal visual motion paradigm in a factorial design. A lateralised interaction was found in the lateral occipital visual processing areas in the avestibular patients. In addition to the known visual-vestibular interaction, this demonstrates a visuo-proprioceptive interaction, which may reflect compensation after vestibular injury. Conclusions: Vestibular perceptual function can be measured in disease, and is elevated in patients with acute peripheral vestibulopathy. Specific psychological and physiological factors associated with clinical recovery after vestibular neuritis are proposed. Functional MRI shows that proprioceptive signals interact with visual motion signals in patients with vestibular failure.

This thesis contributes contemporary knowledge and understanding to the labour process within the English accounting profession. It accomplishes this through an intensive-comparative, qualitative study of the organization of trainee work in six UK accounting firms located in the top fifteen UK firms by turnover. Much literature on the labour process of English accounting assumes that trainees are graduates (Coffey, 1994; Grey, 1994; Anderson-Gough et al, 1998). However recent statistics paint a different picture: almost one in five trainee members of the ICAEW do not have a degree (Financial Reporting Council, 2013). This thesis investigates the perceived reasons for, and organizational opportunities presented by, this change. Organizational justifications for the development and growth of non-graduate routes to a Chartered qualification are found to be principally exploitative in nature, focusing on the drastically reduced wages paid to trainees on non-graduate programmes, as well as elongating the training period (which is characterised by low wages and routinized work) by a minimum of 12 months. The work performed by trainees on non-graduate schemes is found to be almost identical to that performed by graduates, providing strong evidence of the organizationally-developed degradation of trainee work. This degradation, however, is argued to have not had significant effects on the professional value-sets of trainees on non-graduate schemes: they tentatively possess similar aspirations for Chartered membership and to utilise their Chartered credential as a passport to a career in the wider business world. Taken together, these findings act as a retelling of the labour process in English accounting for the twenty-first century. They highlight the degradation of trainee work by organizations and the earlier enacting of the labour process for aspiring professionals. This reorganization also extends our understanding of the changing relationship between organisations, professions and professional service firms.

The aim of this research study was to build upon the continuing interest around the applicability of situational crime prevention to tackle many forms of crime, including organised crimes. Using money laundering as the specific crime type, this study focused on two specific methods, namely cash intensive businesses and the purchasing of high value portable commodities to determine whether situational crime prevention could improve or enhance current preventative measures within the United Kingdom.

The proliferation in improvised performance of chance strategies, game-like scores, playful exercises, one-off collaborations, prepared, new and hacked instruments suggests a ubiquitous commitment to excavate unforeseen creative possibilities that exist beyond the edge of consciousness. Such strategies are deployed to resist mastery and bring forth the possibility for collision out of which fractures emanate allowing the unfamiliar to flow forth. In this research project I draw upon my experience of sitesufficient extradisciplinary performance to unpack the mechanisms at work in these strategies. The proceeding theoretical discourse initially draws upon the interrelated notions of habitus and norm-circles to illuminate the manner in which dispositions to act are inculcated in the individual and conditioned by the socio-cultural environment to which they are exposed. The aesthetics of liminal phenomena reveal the theatre as a site in which to interrogate these habitual behaviours. This discourse is shown to be too narrow to account for embodied disciplinary-specific performance vocabularies, however, further insights are gained from contemporary cognitive science. The theory of autopoiesis specifies that the individual is fundamentally embodied, bringing forth meaning in the world through perceptually guided action. We see that the body permeates cognition, conditioning our understanding of the world. The notions of external scaffolding and epistemic action are introduced and express the way in which the environment is manipulated to empower the individual. The theory of affordances is subsequently deployed to articulate the perceptual and actional fields available to the individual with respect to their environment. Subsequently this discourse enriches our understanding of the way in which environments constitute networks of empowerment. This theoretical discourse is exemplified in the practical experiments conducted during this research project. Performance technologies associated with electronic music are deployed to create environments for collaborative performance – sites that empower the individual as an extradisciplinary performer.

This thesis surveys and interprets the discipline of humanist philology in England in the seventeenth century, with a focus on the period before the Restoration. Its main sources are editions of and commentaries on ancient texts by British humanists (who in some cases were Irish or Scottish, but published in England); historical and philological treatises; correspondence; and manuscript drafts and notes. It extends recent studies on late Renaissance humanist textual criticism and exegesis into the relatively untrodden territory of the British Isles, but it also revises some of the guiding presuppositions of those studies. Firstly, it shifts scholarly focus from the practices of humanist critics to their overarching sense of method. This produces an emphasis on the substantial intellectual differences that divided humanists from each other: over the use of manuscripts and conjectural emendation, for instance. It also complicates the relationship between humanists and theologians, by showing that many, but not all, humanists were more invested in theological modes of reading than has previously been thought; and that theologians produced major works of philological scholarship. Secondly, it interrogates and heavily qualifies the notion that humanist criticism was a historical discipline. It does so by showing that the goals of humanists remained literary-critical as well as historical, well into the seventeenth century, and that they understood their discipline as operating within a broadly Aristotelian philosophical system that did not always lend itself to an understanding of historical particularity or context. Furthermore, their model of sacred history relied on an enduring and robust typological framework that did not disappear with the onset of humanism. Finally, it demonstrates closer affinities between British and continental philology than have been recognized in the past, by showing that humanism across Europe was turning to biblical criticism and patristic scholarship, not only in England. The intellectual and ideological pressure this turn induced, however, along with the rise of new disciplines that owed little to philological research, caused criticism to recede from its central place in English culture during the middle of the century.

Community reparation for young offenders was introduced under section 67 of the Crime and Disorder Act 1998 and it involves the completion of unpaid work, such as painting and decorating, litter picking and graffiti removal. The Youth Justice Board (YJB) places significant emphasis on community reparation as a successful sanction, but concern has been raised about the poor quality of workplace provision and the deteriorating performance of the disposal. Crucially however, there has been no research explicitly focusing on youth justice community reparation within England and Wales. This study, therefore, reviews and integrates the research and evaluation evidence base for both adult community service and youth justice community reparation and as a result, establishes the most comprehensive model for the effective delivery of unpaid work, including the acquisition of employability skills. It then examines community reparation in practice within a single Youth Offending Team (YOT), utilising a combined methods approach and drawing upon the experiences of young offenders and their supervisors. This research shows that community reparation in practice does not match the available evidence base of what is thought to be effective. In particular, the YOT studied has adopted a formulaic approach to workplace allocation, with an over-reliance on low cost menial tasks. As a result, offenders and their supervisors are frustrated that such placements do not provide employability skills, a key factor associated with reductions in reoffending. This study concludes that youth justice community reparation has the potential to be a highly successful re-integrative intervention for young people, but it argues that more attention needs to be paid to the rehabilitative potential of the disposal. The study also suggests there is a need to disseminate an ‘evidenced-based best practice model’ for the successful delivery of community reparation to all YOTs, sentencers and relevant Inspectorate staff. This will contribute to increasing staff awareness and commitment to the disposal, making a valuable potential contribution to reductions in the use of imprisonment and its associated costs.

Knowledge of the intensity of the Earth's magnetic field throughout geological time can deliver a wealth of information regarding the development of the planet. The nature of the geomagnetic field is dependent on processes that occur deep in the Earth's core. By analysing long period changes in geomagnetic field intensity inferences can be made about conditions in the Earth's interior far back into Earth history. The microwave palaeointensity technique is a relatively recent addition to palaeomagnetic investigation. High-frequency microwaves, which are resonant with the constituent magnetic system of a rock, are used to isolate and progressively remove the magnetisation of samples acquired at the time of formation in a controlled manner. By exciting the magnetic system directly, thermal-type experiments can be conducted, whilst minimising the risk of chemical alteration, which is a major cause of experimental failure.

The linear distortion of the edentulous human mandible under functional loading was measured utilizing bilateral, anterior, osseointegrated oral implants as stable markers of bone position. These parasymphyseal implants were connected to a custom-made linear variable differential transducer (LVDT) to allow the recording of changes in mandibular arch width. Custom-made maxillary and mandibular prosthetic splints were manufactured to allow for the introduction of bite force transducers positioned bilaterally and posterior to the LVDT. These recorded biting forces in Newtons simultaneously with the LVDT recording in microns. This made possible further analysis of functional force in relation to the distortion of the human mandible. In total 16 human subjects were investigated from which 14 subjects provided useful data. The results were compared with previous studies which examined distortion of the human mandible during parafunctional activity and studies examining bite force levels in dentate as well as edentulous individuals. The results suggested that the level of distortion of the human mandible in function was similar with that seen in parafunctional activity and was at times was greater. The study also suggested that knowledge of the anatomical form of the atrophic lower jaw could be used to estimate the degree of distortion expected in a particular jaw during function. This, in turn, could inform on the optimal positioning of implants in the anterior of the mandible where the reduction of functional induced lateral stresses are considered important.

Obesity is a significant public health problem in the United Kingdom and many other parts of the world, including some low-income settings. Although obesity prevalence has been rising for several decades, governments have been slow to implement policies that may have an impact at a population level. Numerous socio-demographic factors have been linked with obesity, but are highly intercorrelated, and identifying relevant factors or at-risk population groups is difficult. This thesis uses a graphical modelling approach, specifically Bayesian networks, to model the joint distribution of socio-demographic factors and obesity related behaviour. The key advantages of graphical models in this context are their ability to model highly correlated data, and to represent complex relationships efficiently as network structure. Three separate pieces of work comprise this thesis. The first uses a sampling technique to identify the networks that best explain the observed data, and employs the common structural features of these networks to infer conditional dependencies present between socio-demographic variables and obesity related behaviour indicators. We find determinants of recreational physical activity differ between males and females, and age and ethnicity have a significant influence on snacking behaviour. The second piece of work usesBayesian networks to build a model of health behaviour given socio demographic input, and then applies this to data from the 2001 census in order to provide an estimate of the health behaviour of a real population. The final analysis uses Bayesian network structure to explore potential determinants of body fat deposition patterns and compares the results tothose derived from a Generalized Linear Model (GLM). Our approach successfully identifies the main determinants, age and Body Mass Index, although is not a genuine alternative due to a lack of sensitivity to less important determinants. Beyond the application to obesity, results of this thesis are of a wider relevance to epidemiology as the field moves towards an increased use of Machine Learning techniques. The work conducted has also met and overcome several technical issues that are likely to be of relevance to others exploring similar approaches.

This thesis focuses on the use of both atom transfer radical polymerisation (A TRP) and reversible addition fragmentation chain transfer (RAFT) polymerisation for the synthesis of controlled-structure poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC}-based copolymers for biological applications. A TRP was used to prepare various fluorescent PMPC homopolymers, statistical copolymers and PMPC-poly(2-diisopropylamino)ethyl methacrylate) (PDPA) block copolymers. (Co)polymers were terminally labelled using a rhodamine 6G-functionalisecl ATRP initiator and statistical copolymers were prepared by copolymerising approximately one unit of either rhodamine 6G methacrylate, rhodamine B acrylate or the commercially available fluorescein-O-methacrylate per PMPC chain. Labelled copolymers prepared using the fluorescent methacrylic comonomers exhibited relatively low polydispersities for mean degrees of polymerisation up to 200. A post-polymerisation functionalisation technique was also used to attach commercially available thiol-reactive dyes to (co)polymers containing a central disulfide bond. Con focal microscopy studies revealed that efficient staining of human dermal fibroblast (HDF) cells was achieved within one hour incubation. Depending on the nature of the fluorescent label, organelle specificity was also observed: rhodamine labelled (co)polymers selectively stain the mitochondria, while fluorescein-labelled copolymers were distributed throughout the cellular matrix. MTT assays indicated negligible toxicity for all the (co)polymers after 24 h incubation at 37°C. Finally, uptake inhibition studies indicated that the internalisation pathway of the rhodamine-labelled polymers is energy-dependent and relies on recognition of the PC groups the (co)polymer chains by scavenger receptors on the cell surface. RAFT polymerisation was used to synthesise a series of PMPC macro-chain transfer agents (CTAs) using a range of RAFT CTAs. These syntheses were all well controlled with low polydispersity macro-CT As of varying molecular weights produced. After purification, selected PMPC macro-CTAs could be chain-extended with DPA to produce a series of pH-responsive amphiphilic diblock copolymers. By tailoring the relative block compositions and varying the preparation method, either spherical micelles, cylindrical (or worm-like) micelles or polymcrsomes could be produced. Using pH-induced self-assembly, it was only possible to form spherical micelles (PDPA DP:'S 59), polymersomes (PDPA DP ~ 77), or a mixture of the two phases (POP A DP = 67). Using both thin film rehydration and solvent-exchange techniques, it was also possible to form worm-like micelles. This was the major nano-structure observed when the PDPA DP was 67. Incubation of selected copolymers with HDF cells confirmed negligible cytotoxicity for all the copolymers, irrespective of end-group, DP or morphology. Moreover, it was also possible to deliver rhodamine B octadecyl ester to the HDF cells. These preliminary studies suggest that the internalisation kinetics may depend on the morphology of the nano-structures. Finally, the use of PMPC macro-CT As as steric stabilisers for the aqueous emulsion polymerisation of DPA was investigated. Using several PMPC25 macro-CTAs, a series of PMPC-PDP A nanolatexes were synthesised, for which the mean hydrodynamic diameter increased systematically with PDPA DP. The most stable formulations consisted of POP A DPs above 250. It was possible to encapsulate rhodamine B octadecyl ester during the synthesis of a PMPC2s-PDPA250 nanolatex and deliver it to HDF cells without causing significant toxicity (cell viability> 80 % after 24 h incubation at 37°C). Cross-linking such nanolatexes was achieved by addition of a small amount of dimethacrylate comonomer during the latex synthesis. This resulted in pH-responsive microgels that swelled on lowering the solution pH below approximately 6.5. Incorporation of a disulfide bond into the cross-linker made it possible to cleave the cross-links, causing the copolymer microgels to dissolve molecularly in acidic solution.

LITERATURE REVIEW What do we know about working through foster carers? A review of psychologically based consultancy and training approaches in the UK. RESEARCH PAPER ‘Against the Odds’ : Foster carers’ perceptions of family, commitment and belonging in successful placements. The thesis comprises three sections. The first is a Literature Review covering UK published studies over the past twenty years on psychologically based interventions for foster carers. With increased recognition of the crucial role that foster carers play in promoting the psychological well-being and mental health of children in care, there has been a corresponding proliferation of consultation and training programmes aimed at assisting carers with this task. The Review examines the effectiveness of these, with pointers for further research in this area. The second section describes a qualitative study related to unexpected positive outcome in foster care. The specific aim is the exploration of perceptions of ‘family’, ‘commitment’ and ‘belonging’ in foster carers who are providing a placement for a young person who has succeeded with them ‘against the odds’. The study employs Interpretative Phenomenological Analysis to identify common themes in the carers’ accounts and the findings are presented in the Results section of the paper, followed by discussion and personal reflection on the enquiry process. The implications of what these ‘successful’ carers reveal are considered with a view to the training and support of foster carers generally. References for each of the first and second papers are included after each respectively. The third section consists of Appendices, including a Public Domain briefing paper, quality estimations of the research studies reviewed and tabulated summaries of each article. The participant information and consent relating to the Empirical paper are also included in the third Section, as well as the Interview schedule and examples of two stages in data analysis.

The aim of this thesis was to provide a better understanding of the needs of spider monkeys (genus: Ateles) kept in zoological parks in order to provide an appropriate environment, which enhances the physical and emotional wellbeing of the individuals. This series of studies adopted primarily a physiological approach that entailed measuring cortisol in urine samples collected over a seven year period to assess the impact of a variety of social and environmental conditions. My studies also involved behavioural observations and a questionnaire study to collect information from other zoological parks that maintain groups of spider monkeys. In order to address the aims of my research I first validated an enzyme immunoassay for urinary cortisol which allowed for the activity of the HPA axis to be measured to assess the physiological stress responses in spider monkeys. The first study assessed the impact of visitors on spider monkeys by comparing levels of urinary cortisol collected with visitor numbers and I found an increase in visitor numbers was associated with an increase in cortisol. This was the first time the physiological impact of visitors was investigated and supports behavioural researcher that visitors adversely impact on primates in zoos. The second study I carried out involved a questionnaires to investigate frequency, direction and intensity of aggression in zoo-housed spider monkeys in 55 other zoos around the world. The pattern of aggressions reported indicated severe and lethal aggression was relatively frequent among captive spider monkeys. Adult males were the most frequent actors of aggression and sub adult males were the most frequent targets, contradicting reports from wild spider monkeys. This aggression could be a condition of the management of spider monkeys in the zoos whereby males and normally transferred between zoos contradicting reports from the wild spider monkeys in which females would emigrate on reaching maturity. Next I investigated aggression, reproductive and separation stressors in the spider monkeys housed at Chester Zoo over a seven year period and measured their effects via changes in urinary cortisol prior to, at and following each event. Aggression had the largest effect, with targets and bystanders having the highest levels of cortisol on the day of aggression for severe and lethal aggression, respectively. When examining the reproductive events, cortisol levels were significantly elevated in the mother the week prior to and the day or birth, but were highest for bystander females on the day of birth. In the case of separations, cortisol was elevated when an individual was separated for longer than 24 hours for separations and less than 24 hours for reintroductions. Finally I investigated the replacement of the breeding male in the spider monkeys at Chester Zoo. Although a significant behavioural effect was identified in the adult females, there was little evidence of an increase in urinary cortisol among them. In addition, there were no instances of aggression between the adult males and the juvenile male in the group. Overall conclusions from this study indicate that the group of spider monkeys did demonstrate a varying stress response to a variety of social and environmental stressors associated with elevated cortisol levels and behavioural changes. However, there was no evidence of long term chronic stressors which are normally associated with poor welfare. This indicated that the environmental provided for this particular group of zoo-housed spider monkeys generally allowed for the individuals within the group to cope and adapt. In light these findings the study also makes a number of recommendations regarding the enclosure design, relocated of individuals and the gradual introduction of spider monkeys in zoos. The findings of this study are important as it contributes to our understanding of the physiological responses to stressors in a zoo environment and therefore has implications for animal management. It also identifies potential species specific requirements for the spider monkey that should be considered.

Establishing a compartment fire's area of origin when it has been burning at postflashover conditions is a difficult process. Burn patterns traditionally used by fire investigators following post-flashover fires can be erroneous. This research has looked into the reliability of using the electrical wiring in a building to establish the origin of a fire. Sixty five fully furnished experimental compartment fires were used and the resultant artefacts analysed with various types of microscopy. Nine separate categories of localised metallic "arcing damage" were identified following the experiments. The surface elemental characteristics of the artefacts were analysed and an association was established between the electrical copper conductors and the materials used to fix the electrical wiring to a surface. This research has demonstrated the importance of a clear demarcation area between the localised metallic damage of the conductors and the undamaged area, to determine whether or not localised melting of electrical conductors is due to electrical arcing damage. Correlations were found within the data collected from the experiments that linked the time to arcing events, the approximate temperature at which these events occurred and the circuit protection device operation sequence. No other correlations were revealed. The analysis of the three-dimensional data has indicated that there is a high probability of arcing damage to electrical conductors occurring close to a fire's area of origin. The series of experimental fires with repeated scenarios has validated the reliability of the arc fault mapping methodology.

The principle of Ubiquitous Computing has expanded the possibilities for new types of application. By combining multiple devices and services, users are presented with functionality in more natural and convenient ways. However, its composite nature places an increased strain on the development process. Furthermore, with ever-increasing hardware capabilities comes the expectation and potential for more complex functionality. Without the correct mechanism, developers will be unable to fulfil the requirement for usable, appropriate functionality.

Task-Based Language Teaching has been the subject of a considerable amount of research and writing over the last 25 years and in more recent years has been considered to be one of the current orthodoxies in the field of English Language Teaching in particular. However, in what is sometimes called the "post methods era" in second/foreign language teaching, teachers are less likely to base their practices on any single approach or method. Task-based language teaching as an approach to English language teaching and learning is explored in this thesis in the form of a case study in order to examine the ways that language teachers make use of theory and research presented to them in the professional literature and on training courses. The literature on teacher cognition, expertise and professional knowledge is reviewed. In addition, an account of models and processes of teacher learning, teacher change, and the relationship between research, theory and practice in second/foreign language teaching is developed to provide a backdrop for the empirical investigation. A qualitative research approach was used to gather and analyse observation and interview data. An intensive case study of four teachers was carried out in order to examine the knowledge, beliefs, attitudes and practices of mid-career teachers of English as a foreign language to adults. These are then related to the literature on the task-based approach to language teaching. Findings include the fact that teachers have only indirect access to researchers' and theorists' discussions on the task-based approach and on SLA more generally, and may not be aware of the principles underlying language teaching approaches. Furthermore, teachers draw selectively on aspects of different approaches and combine these with aspects of other approaches. The nature of the relationship between research, theory and practice which is revealed has implications for teacher development, teacher education and the ways in which theory and researchi s disseminatedto languaget eaching professionals.

In this thesis we aim to show the existence of a stationary travelling wave of a generalised stochastic KPP equation driven by a one dimensional Wiener process. Chapter 1 discusses the background of the deterministic KPP equation and some interesting properties when consider Stratonovich noise and convert to the Itˆo noise. Chapter 2 covers preliminaries and background information that will be required throughout the entire thesis. Chapter 3 defines stretching, an important concept throughout this thesis. We show that for any two initial conditions, one more stretched than the other, stretching is preserved with time. We also show that stretching defines a pre-order on our solution space and that the solution started from the Heaviside initial condition converges. In Chapter 4 we show that the limiting law lives on a suitable measurable subset of our solution space. We conclude Chapter 4 by proving that the limiting law is invariant for the process viewed from the wavefront and hence a stationary travelling wave. Chapter 5 discusses domains of attraction and an implicit wave speed formula is shown. Using this framework we extend our previous results, which have concentrated upon Heaviside initial conditions, to that of initial conditions that can be trapped between two Heaviside functions. We show that for these “trapped” initial conditions, the laws converge (in a suitable sense) to the same law as that for the Heaviside initial condition (up to translation). Chapter 6 discusses phase-plane analysis for our equation and we restate the stretching concept within this framework.

This exploratory piece of work has disclosured certain predictive affects associated with a designer's use of risky protocols ('Risky') and cognitive error ('Error'). The implication of this organisational study on risk and cognitive error (Simon, Hillson & Newland, 1997) rests in the potential for theory development in the role of the offshore designer. The focus of this research has been to investigate how designers of hazardous installations, in particular offshore platforms, might influence the design end users' safety performance. The risk paradigm provided the conceptual framework for making sense ofthe designer's attitude to risk. This exploratory research investigates if individual personality differences and the individual perception of risk and other constructs affect cognitive error and the use of certain risky design protocols. This study has extended the use of the Experience Sampling Methodology (ESM) into the complex design enivironment. A sample population of 167 design engineers from 55 design teams was assessed in situ, up to four times per day over four working weeks. The sample that participated in this organisational study was drawn from industrial sectors that involved the high hazard nuclear and offshore oil and gas industry. This research has been conducted in a number of stages, applying both conventional questionnaires and the novel electronic diary based techniques. Questionnaires were used to measure stable factors through individual maturity, such as personality, and an experience sampling methodology, using personal digital assistants that were used to record momentary data. The stable factors were analysed using exploratory factor analysis to derive 14 emergent factors from the six constructs examined. Multilevel hierarchical linear modelling, using HLM6, was applied to these factors and the momentary diary data. Whilst the research was primarily interested in the individual designer, there were certain interactions between the sample units that characterised the multilevel structure of the investigation. The momentary data nested within individuals, and within design teams showed that personality is significant in predicting cognitive error reports and the use of risky design protocols. Analyses indicated that emotionally stable individuals commit fewer errors, whereas extraverted, open and agreeable personality traits and the key job characteristic of job autonomy and the organisational safety climate are significant predictors in the use of risky design protocols.

Short peptides have been designed and synthesised based on the JV-terminus of the p53 tumour suppressor. The crosslinking of these peptides with a thiol-reactive azobenzene crosslinker, optimised for water solubility, builds on previous research that has demonstrated the effective use of this chemical crosslinker in the regulation of a helical peptide structure. Both the crosslinked and uncrosslinked peptides were reported to bind Hdm-2 with high affinity when compared to the wild-type peptide and the isomeric conformation of the attached crosslinker was reported to influence Hdm-2 binding. Although the extent of binding affinity change through crosslinker conformational switching was not as high as intended, this low degree of structural control contributed to the hypothesis that the strength of the peptide interactions with Hdm-2 is enough to overcome the conformational constraints imposed by the crosslinker and that the extent of secondary structure change upon photoswitching may be enhanced by engineering peptides to bind Hdm-2 though with a reduced affinity. The synthesis of Hdm-2 mutants designed to possess a reduced affinity for p53 further supported this proposal. The design of Hdm-2 binding peptides based on a polyalanine scaffold was explored, since polyalanine forms a stable a-helix. The substitution of alanine residues in the appropriate positions respective to one-another with key p53 residues critical to Hdm-2 binding in addition to cysteine residues to enable the attachment of the azobenzene crosslinker led to the development of peptides with Hdm-2 binding affinities comparable to wild-type p53.

This thesis examines the spoken and written discourse of uniformed British police officers. Utilising a rhetorical and discursive analysis, the study considers firstly how officers use their considerable powers of discretion to deal informally with crime and criminal incidents. Focusing on a form of discretion that the police refer to as cuffing, two specific discursive practices were identified as being used by police to informally resolve crime: these were the giving of suitable advice and the that's civil device. The second part of the study was concerned with the formal prosecution process and how officers construct prosecution case files. Specifically, how they reformulate and precis evidence in 'domestic' violence cases to assist a Crown prosecutor in making a charging decision. In this normally confidential and non-public discourse, officers rely upon a very narrow range of linguistic devices and speech genres; these are combined with an equally limited array of gendered stereotypes and legal myths, with the result that prosecution cases can be 'subverted' (Sacks 1995) and thus discontinued. In both studies, the doing of policing was consistent with two occupational ideologies that are influential within police operational subcultures: the ideology of pragmatism and the ideology of self-preservation. The findings raise concerns about some of the working practices of the police.