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Obesity represents a serious threat to health which can be reduced by volitional control of eating and physical activity behaviour. Social cognition theories propose that such behaviour is influenced by cognitions regarding its desirability. The role of obesity outcome expectancies in predicting weight control behaviour has not been established and there are no psychometrically sound measures of these constructs. This thesis aimed to investigate the relationship between knowledge and beliefs regarding obesity's consequences and weight control Intentions in obese patients. The Obesity Risk Knowledge Scale (ORKS-10) was developed using item analysis and rigorously evaluated in a large population (n=965). The ORKS-10 scale proved to be a short, reliable and valid measure of knowledge regarding the health risks associated with obesity. In addition, thematic analysis of data from focus groups and structured interviews was used to identify 41 salient items for a scale to measure obesity outcome expectancy beliefs. Factor and item analysis were then used to develop the Obesity Outcome Expectancy Beliefs Scale (ObEx-15). The ObEx-15 comprises three reliable and unidimensional subscales; the Health Benefits of Weight Control (HBen), Social and Aesthetic Benefits of Weight Control (SABen) and Costs of and Barriers to Weight Control (Cost). Obese adults were recruited from weight management clinics (n=110, response rate=54.19%). Multiple regression analysis indicated that weight control intentions were most strongly associated with endorsement of the social and aesthetic consequences of obesity (B=0.117, t104=2.314, p<0.05) and rejection of the costs and barriers of weight control (B=0.088, t104=2.273, p<0.05). Participants had low levels of knowledge about obesity's health risks and neither ORKS-10 scores nor HBen scores were associated with intentions. Health promotion might, therefore, benefit from focusing upon obesity's non-health impacts and the costs and barriers of weight control. Future obesity outcome expectancies research will also profit from the availability of psychometrically sound measures.

The incorporation of the Imitatio by Protestant and Catholic reform movements suggests important points of continuity between late medieval and early modem religion, especially within the realm of spirituality. The study of the Imitatio is testimony to the versatility of spirituality; it was accessible both to the laity and monks and also to Protestants and Catholics. The ethical emphasis of the Imitatio, its interiority, its simplicity and intended renewal in Christ, were vital to its endurance. The text's accessibility was reinforced by the expansive nature of late medieval and early modem translations. English and French translations of the Imitatio at the turn of the sixteenth century reflected the concern for simplification, thereby simplifying the text rather than providing an alternative interpretation. In the sixteenth century, Protestant translators, grounded in the essential tenets of Lutheran theology, inevitably revised or removed any explicitly Catholic elements of the Imitatio's spirituality. Despite its apparent widespread appeal, the promotion of the Imitatio tended to be undertaken by late medieval and early modem movements which had links with the devotio moderna. The Imitatio was circulated in late medieval England and France by individuals whose connections with the devotio moderna were marked. Indeed, a similar trend was evident with the Protestant tradition of the text; Leo Jud, Caspar Schwenckfeld and Sebastian Castellio were all directly or indirectly influenced by the Brethren. Most striking of all was the timing with which translations of the Imitatio appeared. The translations by Caspar Schwenckfeld, Leo Jud, Edward Hake and Thomas Rogers were undertaken at a critical stage of their respective Reformations. Similarly, the Jesuits, traditionally viewed as the vanguards of the Counter- Reformation, were deeply committed to the Imitatio. Devotional works were vital to the maturing progress of Reformations, regardless of the confession. Spirituality was not a peripheral, insignificant dimension of religion; it remained at the very centre of Protestant and Catholic self-perception and identity.

Le présent travail a pour but d'évaluer les potentialités électrocatalytiques du cuivre sous différentes formes pour les réactions de réduction du dioxyde de carbone et de réduction de l'ion nitrate. Dans la première partie du travail, nous avons comparé, à l’aide de la voltampérométrie, d’électrolyses à potentiel contrôlé et d’analyses chromatographiques, l'activité d'électrodes polycristalline et monocristallines de Cu et d'alliages AuxCuy de différentes orientations cristallines pour l'électroréduction de CO2. Nous avons pu établir une étroite corrélation entre l'activité de l'électrode de Cu et l'arrangement atomique de sa surface. L'activité et la sélectivité pour CH4 de Cu décroissent selon la séquence : Cu (111) > Cu (100) > Cu (poly). La réduction du CO2 et la formation de CH4 sont favorisées sur les surfaces lisses et denses à l'échelle atomique. La sélectivité des alliages AuxCuy est considérablement orientée vers CO quand la fraction superficielle de Au augmente. L'alliage de composition 50-50 conduit à la formation exclusive de CO. La seconde partie de la thèse est consacrée à l'étude de l'activité d'électrodes massives de Cu polycristallin et monocristallin d’orientation (111) et de dispersions de Cu pour la réduction électrochimique de NO3-. Nous avons mis en évidence l'importance des conditions de pH pour le déroulement des processus à l'électrode de cuivre. En milieu acide, NO3- est directement réduit en NH4+ alors qu’en milieu neutre, les réactions de réduction de NO3- en NO2- et de NO2- en NH4+ s’observent successivement en fonction du potentiel. L'activité des dispersions de Cu dans un film de polyaniline dépend fortement des conditions de dépôt. Le cuivre incorporé au film sous sa forme réduite est plus actif que le cuivre incorporé au film initialement oxydé. Par ailleurs, nous avons montré que la concentration de H+ dans le polymère est limitée. En conséquence, le processus de réduction de NO3- sur le cuivre dispersé dans un film de polyaniline est modifié en milieu acide. L’utilisation d’un film de poly-3,4-éthylènedioxythiophène déposé sur une surface de Pt s'est quant à elle révélée inadéquate comme support pour l'incorporation de Cu dans le cadre de l'étude de la réduction de NO3- en milieu acide.

Classical coeliac disease (CD) is a well-defined syndrome of small bowel villous atrophy associated with abdominal pain, malabsorption, and weight loss as a result of gluten-sensitivity, reversed rapidly by gluten exclusion diet. Disease associations include dermatitis herpetiformis (DH), Addison’s disease, type 1 diabetes mellitus, autoimmune thyroid disease and a variety of neurological disorders. This thesis aims to investigate the hypothesis of the existence of a gluten sensitive neurological disease CD with coexistent neurological dysfunction is only rarely reported in a neurological setting. 23 cases were reported from the British Neurological Surveillance Unit (BNSU) over 24 months and 13 locally over 31 months. 18 sets of notes (50%) were reviewed. These patients comprise a heterogeneous group of neurological disorders including epilepsy, myelopathy, axonal neuropathy and migraine. Neurological disorders in patients with confirmed gluten sensitivity may occur simply by chance. In a cohort of 801 CD patients, 54 neurological disorders were identified in 177 patients including stroke (2.9%), migraine (2.7%), epilepsy (2.6%) and carpal tunnel syndrome (2.0%). More detailed investigation of 35 patients with DH and 53 patients with CD, confirmed a low prevalence of idiopathic neurological abnormalities (DH 11%; CD 25%). Analysis of sera from these patients did not identify the presence of anti-neuronal antibodies. A novel anti-spinal antibody was identified in over 50% of the subjects with DH but this requires further characterisation. It has been postulated that patients with idiopathic neurological disease and anti-gliadin antibody (AGA) seropositivity are gluten sensitive. However, AGA lacks disease specificity being found in 10% of healthy blood donors. Screening of 49 unselected multiple sclerosis cases found IgG AGA in 12% of patients and 13% of blood donors confirming that AGA (especially IgG isotype) can be a non-specific finding. AGA, other food antibodies and tissue transglutaminase antibody (TTG) were measured in patients with idiopathic ataxia (20), hereditary ataxia (7) and idiopathic peripheral neuropathy (32). None of the cases was positive for IgA TTG making occult CD unlikely. Cerebellar ataxia with positive AGA (so-called ‘gluten ataxia’) was rare (4 cases in 2 years from a population of 2 million). All food antibodies tested (AGA, hen’s egg albumen, and cow’s milk lactoglobulin), particularly IgG, were a common finding in both ataxia and peripheral neuropathy groups. This study found no evidence for gluten neurotoxicity. Serological tests, particularly AGA, need to be interpreted with caution. Further study is required regarding the nature of the association between neurological illness and gluten sensitivity.

The lower mean levels of total cholesterol, LDL cholesterol, fibrinogen; the higher likelihood of being from more affluent social class; and the small but significant rise in HDL cholesterol and reduction in blood pressure amongst coeliacs presenting with gastrointestinal symptoms observed following treatment with a gluten-free diet suggests coeliacs have favourable vascular risk profile features in comparison to the general population. However, the higher likelihood of having abdominal truncal obesity amongst incident coeliacs that only worsens following treatment with a gluten-free diet together with the higher proportion of measured systolic hypertension amongst male coeliacs suggests that there are also potentially adverse vascular risk profile features associated with celiac disease. Though incident coeliacs with silent disease reported no change in their quality of life prior to diagnosis of coeliac disease, silent coeliacs were as likely to have villous atrophy and physiological derangement to those coeliacs presenting with symptoms or with classic features of coeliac disease. The quality of life reported by coeliacs presenting with silent disease, classic disease and with gastrointestinal symptoms was worse than that observed in the general population. A year's treatment with a gluten-free diet resulted in coeliacs having similar or in some components better quality of life than that observed in the general population. The rate of change of quality of life was similar amongst those coeliacs with silent, classic or symptomatic disease. The breast cancer risk profile suggests both protective and adverse associations of coeliac disease. The higher proportion of women being parous, having their first full-term pregnancy before 30 years and breastfeeding in addition to the younger mean age at menopause suggests women with coeliac disease have favourable breast cancer risk profile features in comparison to the general population. However, the higher likelihood of being Caucasian and of affluent social class together with higher proportion having early menarche and irregular menstrual cycles suggests there are also potentially adverse breast cancer risk profile features associated with celiac disease. Conclusions Persons with mild enteropathy disease have few physiological derangements at diagnosis of coeliac disease and show no important biochemical change following treatment with a gluten-free diet in comparison to those with severe enteropathy coeliac disease. The prevalence of hypertransaminasaemia is lower than previously reported which may be reflective of differences in study design or contemporary coeliac disease involves a milder spectrum of disease. The observed vascular and breast cancer risk profile suggests both protective and adverse associations of celiac disease and on treatment with a gluten-free diet results in an attenuation or indeed reversal of the vascular risk profile in some co-variates. Silent coeliac disease is associated with a reduction with quality in life which improves like in symptomatic and classic disease with treatment with a gluten-free diet. Incident coeliac disease is associated with more affluent social class.

The evidence for genetic contributions to the development of asthma and atopy has been well established. Refining the major genetic factors underlying these contributions will lead to a greater understanding of the pathophysiology of these conditions and potentially identify novel therapeutic targets. This thesis describes a series of studies designed primarily using genome-wide association (GWA) approaches to examine common single nucleotide polymorphisms (SNPs) contributing to these phenotypes in the Caucasian population. Susceptibility to atopy was assessed using both non-parametric association tests of SNPs across the genome and focused analysis of two regions on chromosomes 3p22.1-q22.1 and 17p12-q24.3 previously identified through a meta-analysis of genome-wide linkage studies (GSMA). The discovery cohort consisted of 1,083 cases and 2,770 controls, replication analyses were undertaken in four independent population cohorts. A GWA study of severe asthma was carried out in 933 cases and 3,346 controls with replication in a further 231 cases and 1,345 controls. The contribution of SNPs within all previously reported asthma susceptibility loci identified using a comprehensive literature search was also evaluated. Overall, there is evidence for a large number of loci influencing both atopy and severe asthma, each harbouring modest effects. A number of potentially novel loci meeting nominal significance in both GWA studies have been identified requiring further work. Strong evidence was found to support the IL1RL1-IL33 signalling pathway in asthma pathogenesis. Molecular characterisation of the 5’ untranslated regions of IL1RL1 and IL33 suggest a complex regulatory role of identified common variants involving multiple promoters for IL1RL1. A number of asthma specific variants within the chromosome 2q12 and 9p24.1 regions were detected using next generation re-sequencing in homogenised pools of cases and controls warranting further analyses. This work has identified a potentially important pathway in which to focus the development of effective asthma therapies. Future directions will include functional analysis of replicated variants and tests of interactions between the multiple genetic and environmental factors likely to be involved in disease.

Latest epidemiological data suggests that 1.5 billion adults worldwide are obese or overweight. Excess weight and adipocyte hypertrophy have long been associated with contributing to low-grade systemic inflammation through elevated adipokine secretion. These increased endocrine signals further augment the metabolic dysfunction related to the presence of obesity. A chronic exposure to obesity mediated inflammation is also suggested to be responsible for progression of renal pathology and eventual end-stage organ failure. In human clinical statistics, these factors indicate a gender disparity, as males demonstrate much faster progression rates of obesity-linked renal disease than females. Therefore, the aim of this thesis was to investigate the role of gender in obesity mediated inflammation in the development of renal disease using a large animal model i.e. sheep. Post-natal female and male sheep were exposed to a lean or obesogenic environment by restricting physical activity from ≈3 months to ≈17 months of age. Analysis of body composition and adipose tissue physiology, morphology and deposition identified the development of moderate obesity following chronic exposure to a low physical environment, although no differences were observed with gender. With obesity, both genders demonstrated metabolic irregularities; males showed hyperinsulinaemia and females displayed hypercortisolism. Gene expression analysis identified an up-regulation of inflammatory related genes in perirenal adipose tissue (PAT) and kidney in obese males, a finding not seen in females, although obese females exhibited an up-regulation in glucocorticoid receptor abundance in PAT. Furthermore, the males demonstrated adaptations in renal structure and function with obesity, modifications not observed in females. The main conclusion of my thesis is that after the development of obesity, males appear much more sensitive to the metabolic, inflammatory and renal adaptations associated with an obese condition. Females displayed a down-regulation of inflammatory genes with obesity which I propose acts as a protective mechanism against the progression of renal disease, perhaps mediated by an immunosuppressive glucocorticoid action in adipose tissue. It is also possible that sex hormones play a role in obesity inflammatory renal disease development, postulated to occur through HPA activation and epigenetic alterations.

Obesity continues to be a major cause of morbidity and mortality and worldwide prevalence rates continue to rise. The cornerstone for treating obesity remains diet and lifestyle, with the ultimate goal being normalising those parameters that are associated with ill health, for example hyperinsulinaemia and insulin resistance. Because obesity predominantly develops due to a mismatch between energy intake and utilisation, this thesis looked at the effects of dietary interventions upon Resting Energy Expenditure (REE) and substrate oxidation. In addition, the impact of popular dietary interventions upon body composition and insulin resistance was examined. When phenotypic characteristics were investigated before and after weight loss by using hypocaloric diets, which differed in fat and carbohydrate content, Fat-Free Mass (FFM) and Fat Mass (FM), were strong predictors of REE before and after the intervention and weight loss rather than the specific dietary intervention, significantly predicted post intervention REE. Fasting fat oxidation was found to be lower in obese subjects and they had a lower postprandial response to a high fat challenge. This implied that a diet high in fat is more likely to promote a positive energy balance an ultimate weight gain. The final study compared 4 popular dietary interventions. Each was equally effective at achieving clinically significant weight loss and improvements in insulin sensitivity. Although none was significantly more superior, there was a trend supporting three of the diets (Atkins’, Weight Watchers and Rosemary Conley) above the other (Slim-Fast) and it was the pattern of weight loss, i.e. mainly loss of FM, which proved beneficial with regards to improving insulin sensitivity. In summary, this thesis confirms that REE is mainly predicted by FFM and FM and that there is diminished fat oxidation on obese subjects. What this thesis also adds to previous research that it if a specific diet can improve the pattern of weight loss, this can be clinically beneficial.

This thesis investigates the topological reconstruction problem, which is inspired by the reconstruction conjecture in graph theory. We ask how much information about a topological space can be recovered from the homeomorphism types of its point-complement subspaces. If the whole space can be recovered up to homeomorphism, it is called reconstructible. In the first part of this thesis, we investigate under which conditions compact spaces are reconstructible. It is shown that a non-reconstructible compact metrizable space must contain a dense collection of 1-point components. In particular, all metrizable continua are reconstructible. On the other hand, any first-countable compactification of countably many copies of the Cantor set is non-reconstructible, and so are all compact metrizable h-homogeneous spaces with a dense collection of 1-point components. We then investigate which non-compact locally compact spaces are reconstructible. Our main technical result is a framework for the reconstruction of spaces with a maximal finite compactification. We show that Euclidean spaces &reals;ⁿ and all ordinals are reconstructible. In the second part, we show that it is independent of ZFC whether the Stone-&Ccaron;ech remainder of the integers, &omega;&ast;, is reconstructible. Further, the property of being a normal space is consistently non-reconstructible. Under the Continuum Hypothesis, the compact Hausdorff space &omega;&ast; has a non-normal reconstruction, namely the space &omega;&ast;&bsol;&lcub;p&rcub; for a P-point p of &omega;&ast;. More generally, the existence of an uncountable cardinal &kappa; satisfying &kappa; = &kappa;^&lt;&kappa; implies that there is a normal space with a non-normal reconstruction. The final chapter discusses the Stone-&Ccaron;ech compactification and the Stone-&Ccaron;ech remainder of spaces &omega;&ast;&bsol;&lcub;x&rcub;. Assuming the Continuum Hypothesis, we show that for every point x of &omega;&ast;, the Stone-&Ccaron;ech remainder of &omega;&ast;&lcub;x&rcub; is an &omega;₂-Parovi&ccaron;enko space of cardinality 2^{2^c} which admits a family of 2^c disjoint open sets. This implies that under 2^c = &omega;₂, the Stone-&Ccaron;ech remainders of &omega;&ast;&bsol;&lcub;x&rcub; are all homeomorphic, regardless of which point x gets removed.