The thesis is a study of consumer participation, focussing on a case study of MIND. Data were collected from interviewing, participant observation and examination of records. The following are the main conclusions. In order to understand consumer participation, and effectively to increase it, it is necessary to be aware of: the different types of such involvement; the extent to which it includes opposition or collaboration with people in authority; the various types of participant; and the levels and degrees of participation. Levels vary from involvement in decisions about the individual's own care to Central Government policy-making; whilst degrees of participation range from information to the total running of an organisation. Also important is the extent to which consumer participation is openly declared, conscious, and formal or informal. This was found to vary considerably within MIND. MIND has its origins in a beneficent organisation, but from the nineteen seventies, increasing efforts were made to facilitate consumer participation. Almost all respondents were in favour of this, but there was considerable uncertainty about the most effective means to facilitate such involvement, and doubts about whether proposed policies for its implementation would be successful. Respondents often mentioned psychological gains and the value of individuals' skills and abilities as benefits of consumer participation. However, difficulty in taking on responsibility was frequently said to result in problems. The attitudes and aptitudes of members with experience as consumers or mental health professionals, and the personal influence of National/Regional MIND staff, were seen as crucial in facilitating or hindering consumer participation, as were organisational factors such as the structure of meetings, the complexity of functions, and the relationship between different levels of MIND, which resembled Rhodes' description of central–subcentral government relations. The influence of National/Regional MIND on Local Associations was limited because the latter were autonomous charities. The thesis also covers methodological and ethical problems, and the implications of the finding for implementing policies to increase consumer participation in voluntary organisations.

Growing evidence suggests that dietary n-3 very long chain polyunsaturated fatty acids (eicosapentaenoic acid; EPA and docosahexaenoic acid; DHA) reduce the risk of coronary heart disease and stroke, alpha-linolenic acid (alpha-LNA) is the natural precursor of EPA and DHA and is an abundant and accessible source of dietary n-3 PUFA that can be further elongated and unsaturated in vivo. The overall aim of the project is to examine the conversion of alpha-LNA to its long chain metabolite, most importantly DHA. This aim was accomplished by a combination of a human dietary intervention study to assess accumulation of EPA and DHA from dietary alpha-LNA, and 13C-tracer studies of alpha-LNA & linoleic acid (LA) conversion to their long-chain metabolites. The dietary intervention trial was a 12-week parallel design in men expressing an atherogenic lipoprotein phenotype, a common source of lipid-mediated coronary heart disease risk. Diets were enriched with 18 g of alpha-LNA as flaxseed oil (n=21), with a high LA oil (n=17), or with fish-oil (6g/d n=19) as a positive control group. Thus the intention was to provide an increased intake of alpha-LNA with a low ratio of n-6 to n-3 PUFA (1:1 or less), minimizing competition between alpha-LNA and the abundant LA and, in theory, increasing the conversion of alpha-LNA to LC n-3 PUFA. The results from the dietary intervention indicate that, dietary alpha-LNA as flaxseed oil can increase n-3 membrane fatty acid contents, through a 3-fold increase in alpha-LNA (p <0.001)) and 2.5 fold increase in EPA (p<0.001) at week-12, decreasing in n-6:n-3 ratio (p =0.001), but not changing DHA level. In contrast the fish oil diet increased both EPA and DHA. Dietary alpha-LNA had 7% of the efficacy of preformed EPA from fish oil to increase membrane EPA levels. Subjects on the 13C tracer study were a sub-group of the intervention study, studied after 12-weeks on the high alpha-LNA (n=6) or high n-6 (n=5) diets. Subjects were given an oral mixture of 400 mg each of uniformly 13C labelled alpha-LNA and LA in a milk shake after an overnight fast. 13C enrichment was measured in fatty acids isolated from plasma at 1,2,3,7,10 and 14 days after the dose. Of the dose appearing in the plasma 35-45% was converted to EPA with no dietary effects. Some conversion to DHA did occur especially in the high n-6 group (3.9% of dose) compared with the flaxseed-oil group (mean value 0.8% of the dose; p < 0.05). In the single subject studied on the fish-oil diet there was a much lower conversion rate compared to the flaxseed-oil diet. The variability between subjects for percent conversion to DHA ranged from zero to 6.2% of the dose appearing in plasma. Taken together these results clearly establish the effectiveness of dietary alpha-LNA as a method of increasing the concentration of EPA, but not DHA, in membrane phospholipids, with up to 7% of the efficacy of preformed EPA. The increase in the EPA: AA ratio (eicosapentanoic: arachidonic acid) in membrane phospholipids with dietary alpha-LNA is likely to reduce the overall inflammatory environment with beneficial effects for long-term health.

In adopting a tabula rasa approach, this study sought to determine those elements of care that should be prioritised in the service provision for families with children who have cancer. An innovative approach was adopted, as opposed to a conventional thesis structure, in which the literature in this study was used both as a means of informing the research rationale and design as well as being a data source in its own right and precluded providing a conventional literature review. Conventionally a thesis contains an introduction, chapters that review the literature, describe the methods, present results and ends with a discussion and conclusions. However, because there are many different elements to this thesis it is intended to structure it differently. Given that each form of data requires a different form of analysis, each data source has its own chapter. The reader will therefore find chapters headed The Professional Literature, The Charity Leaflets, and The Delphi Study. Furthermore, within each chapter methodological considerations, and the reasons for the methodological decisions taken are discussed. These are made in the appropriate places. Three sources of data were investigated including the professional and relevant charity leaflets literature and a Delphi study was undertaken to obtain the views of both professionals («=31) and families («=15). A content analysis was conducted for the first two sources of data and the first round of the Delphi study. All sources were essential in compiling a comprehensive list of desirable elements of care. The salient elements of care from the three sources of data were synthesised in order to identify elements that were common to all data sources. The elements of care were grouped under six headings as categories with relevant subcategories. The main categories were 'Communication and Cooperation', 'Maintaining Normality', 'Professional Issues', 'Research', 'Resources and 'Treatment Issues' for the professional literature and charity leaflets. Inter-rater reliability was established indicating a high level of agreement between both raters (Kappa = 0.677 and 0.958 respectively, p < 0.001 in both cases). 'Partnership in Care' was the analytical framework devised from the government directives of involving patients and their carers more in the healthcare process. The framework adopted was based on the families' participation as informed, decision making and empowered families. The framework was then used as a means by which the data for all three sources could be summarised, compared and contrasted. This then enabled a comparison between the service provision advocated for children with cancer and what the Delphi study of the families' opinions had highlighted. Given the rhetoric of policy directives in involving the family more in participation of care, the findings have shown that there is a disparity between the perspectives of the families and professionals. In line with policy directives, the professionals had prioritised the involvement of families as partners. However, their commitment to the partnership is questionable, as they did not regard more training in understanding the impact of the disease on the family as important. The main emphasis was on clinical service provision in terms of dedicated adolescent units in regional centres and emergency contact provision. The families placed an emphasis on communication in terms of their contact with the GP in avoiding late diagnosis, having a key worker, providing continuity between hospital and home, and training courses for the professionals to better understand the impact of the disease in the family. By contrast the professionals placed an emphasis on clinical provision namely age appropriate environment for care and 24 hour emergency contact and input from regional units. The findings suggest that in reality, families cannot always be equal partners with the professionals, nor do they necessarily wish to be. From the families' perspective a partnership in care has been defined as mutual respect, advocacy, encouragement, and having continuity of care between hospital and home, given by practitioners who have the expertise and who understand the impact of the disease on the family.

La roche argileuse, constitué par des minéraux comme l'argile, le quartz et la calcite, etc., est un milieu poreux typique sous enquête dans le monde entier dans l'ingénierie pétrolière, le stockage souterrain de déchets et de la science de l'exploitation minière. Il est important de caractériser les roches argileuses par des approches multi-échelles depuis son comportement mécanique et les propriétés physiques sont étroitement liées à la microstructure et les compositions minéralogiques. La présente thèse est consacrée à l'enquête micromécanique des argiles synthétiques artificielles obtenues par des essais de consolidation à haute pression dans le laboratoire avec la composition minérale et de la porosité sous contrôle pour réduire au minimum l'affection de la complexité des microstructures comme dans la nature argilo roches. essais de compression triaxiale avec des cycles de chargement-déchargement sont effectuées pour caractériser les comportements mécaniques et les propriétés de transport des fluides des argiles synthétiques. Le dispositif et les méthodes expérimentales développées sont ensuite utilisées pour caractériser la couche de roche argileuse morts-terrains dans une ingénierie pétrolière en Angola. Les données expérimentales permettent enfin l'application et la validation d'un modèle constitutif micromécanique à base de caractériser et de prédire les comportements mécaniques des argiles synthétiques. / Clayey rock, constituted by such minerals as clay, quartz and calcite, etc., is a typical porous medium under investigation worldwide in petroleum engineering, underground waste storage and mining science. It is important to characterize the clayey rocks by multi-scale approaches since its mechanical behavior and physical properties are closely related to its microstructure and mineralogical compositions. The present thesis is devoted to micromechanical investigation of the man-made synthetic clays obtained by high pressure consolidation tests in laboratory with mineral composition and porosity under control to minimize the affection of microstructural complexity as in nature clayey rocks. Triaxial compression tests with loading-unloading cycles are carried out to characterize both the mechanical behaviors and fluid transport properties of the synthetic clays. The developed experimental device and methods are then used to characterize the overburden clayey rock layer in a petroleum engineering in Angola. The experimental data finally allow the application and validation of a micro-mechanics based constitutive model to characterize and predict the mechanical behaviors of the synthetic clays.

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Informe de Seminario para optar al grado de Licenciado en Historia / Seminario de Grado : Sociedad y política en el mundo greco-romano

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Introduction: Globally, around 2.6 billion people have consumed alcohol in 2017. In the same year, nearly 3 million or 5% of all deaths were attributable to alcohol consumption, the majority of which were non-communicable diseases, such as cancer, digestive and cardiovascular diseases. Chronic heavy alcohol consumption in particular causes harm to the cardiovascular system and is linked to an elevated risk on the occurrence of ischemic heart diseases and cardiomyopathies. The latter constitutes a heterogeneous group of cardiovascular diseases, which can generally be characterized by a weakened heart muscle. The causal link between chronic heavy alcohol consumption and cardiomyopathy has long been recognized, with the Tenth Revision of the International Classification of Diseases (ICD-10) listing alcoholic cardiomyopathy (ACM) as a fully alcohol-attributable diagnosis. For a few, predominately high-income countries, civil registries provide valuable information of ACM mortality. However, for the majority of countries and global population, the cardiomyopathy burden attributable to alcohol consumption needs to estimated. Established methods for estimating alcohol-attributable fractions (AAF), i.e. proportion of an outcome which could be avoided in a scenario of zero alcohol consumption, could not be applied for cardiomyopathy as the link between alcohol consumption levels and risk of cardiomyopathy could not be specified. Accordingly, a global assessment of the contribution of alcohol consumption to the disease burden from cardiomyopathy was lacking. Aims and objectives: First, to develop methods for estimating the contribution of alcohol consumption to cardiomyopathy that can be used globally (study I). Second, to apply the method developed in study I to estimate the global mortality from ACM (study II). Third, to assess differences between this method and an alternative method for estimating the contribution of alcohol consumption to cardiomyopathy proposed during pursuit of these aims (study III). Design: Statistical modelling study with country-level data as unit of analyses. Study I. Based on mortality data from civil registries, the proportion of deaths from ACM among deaths from any cardiomyopathy (=AAF) was used as proxy for the link between alcohol consumption and cardiomyopathy. To generalize this link to countries without available civil registry data, associations of population alcohol exposure and registered AAF were established. Cardiomyopathy deaths that are attributable to alcohol use were quantified in those countries with available registry data. Study II. For countries without available civil registry data, ACM mortality was estimated using population alcohol exposure data based on the methods from study I. As a result, national, regional and global estimates of the mortality attributable to ACM were obtained for the year 2015. Study III. In the alternative method developed by the Global Burden of Disease (GBD) study team, the contribution of alcohol consumption to cardiomyopathy was estimated taking into account that actual ACM deaths may be incorrectly coded as so-called garbage codes (disease codes that do not accurately describe the underlying cause of death). In the alternative method, garbage codes were redistributed to both cardiomyopathy and ACM using statistical procedures. The underlying assumptions for the redistribution of garbage codes were examined by comparing registered and estimated ACM mortality data taking into account the distribution of alcohol exposure. Data sources: Data on population alcohol exposure (alcohol per capita consumption, prevalence of heavy episodic drinking, prevalence of alcohol use disorders) were sourced from publicly available World Health Organization (WHO) data bases. As outcome data, sex-specific mortality counts from different disease groups (ACM, any cardiomyopathy, and selected garbage codes) were obtained at the country level from three different sources: First, WHO mortality data base, which provide civil registry mortality data on nearly half of all member states, coded according to the ICD-10. Second and third, ‘Global Health Estimates’ and ‘GBD Results Tool’ data bases, which provide complete and consistent mortality estimates aggregated into larger disease groups for all WHO member states. Data on covariates were obtained from the United Nations and the World Bank. Statistical analyses: In study I, the dependent variable – AAF for cardiomyopathy – was calculated by dividing deaths from ACM by deaths from any cardiomyopathy, based on civil registry data from N=52 countries. Taking into account country-specific crude mortality rates of ACM, AAF were modeled in two-step sex-specific regression analyses using population alcohol exposure as covariate. AAF were estimated for the same set of N=52 countries, in addition to N=43 countries without civil registry data. Estimated AAF were compared to registered AAF available for N=52 countries. In study II, the global mortality of ACM was estimated by combining civil registry ACM mortality data for N=91 countries and estimated ACM mortality for N=99 countries without available civil registry data. For the latter set of countries, ACM mortality data were calculated by estimating AAF based on the methodology outlined in the first study and subsequently applied to all cardiomyopathy deaths. As a proxy for under-reporting of ACM in civil registries, estimated ACM deaths were compared to registered ACM deaths for N=91 countries. In study III, ACM mortality estimates from the GBD study were compared against registered ACM mortality data for N=77 countries, aiming to test underlying assumptions for redistribution of garbage-coded deaths in the alternative method. For this purpose, descriptive statistics and Pearson correlations were used to assess the association of estimated and registered deaths and to examine consistency of estimates with population alcohol exposure. Results: In study I, population alcohol exposure and ACM mortality were closely linked (spearman correlation=0.7), supporting the proposed modelling strategy. For N=95 countries, the AAF for cardiomyopathy was estimated at 6.9% (95% confidence interval (CI): 5.4-8.4%), indicating that one in 14 of all cardiomyopathy deaths were attributable to alcohol in the year 2013 or the last available year. The findings were robust, with 78% of all estimated AAF deviating less than 5% from registered AAF. In study II, it was estimated that 25,997 (95% CI: 17,385-49,096) persons died from ACM in 2015 globally, with 76.0% of ACM deaths being located in Russia. Globally, 6.3% (95% CI: 4.2-11.9%) of all deaths from cardiomyopathy were estimated to be caused by alcohol. Furthermore, indications of underreporting in civil registration mortality data were found, with two out of three global ACM deaths being possibly misclassified. In study III, findings suggested that only one in six ACM deaths were correctly coded in civil registries of N=77 countries. However, the algorithm accounting for misclassifications in the GBD study was not aligned with population alcohol exposure, which has led to implausibly high ACM mortality estimates for people aged 65 years or older. Specifically, registered and estimated ACM mortality rates diverged in the elderly, which was corroborated with decreasing correlations in these age groups. Conclusions: For countries without civil registry data, the contribution of alcohol consumption to mortality from cardiomyopathy could be quantified using population alcohol exposure and estimated mortality data for any cardiomyopathy. The proposed method was adapted by the WHO in 2018, allowing for a more complete picture of the alcohol-attributable global disease burden for nearly 200 countries. Notably, ACM mortality was hardly present in countries with low to moderate alcohol consumption levels, corroborating that ACM is the result of sustained and very high alcohol consumption levels. In civil registries, at least two out of three ACM deaths are misclassified, thus, presented mortality figures are likely underestimated. As with other alcohol-attributable diseases, misclassification of ACM mortality is a systematic phenomenon, which may be caused by low resources, lacking standards and severe stigma associated with alcohol use disorders. With transition from ICD-10 to ICD-11, new methods will be required as ACM will not remain a unique diagnosis in the new classificatory system. Future methods should account for mortality misclassifications by redistributing garbage codes while taking into consideration the distribution of alcohol exposure. Further, measures to reduce stigma may improve diagnostic accuracy for ACM and other alcohol-attributable diseases. This will not only improve public health statistics but also – and more importantly – improve health prospects of persons with heavy alcohol consumption.:Statement for a publication-based dissertation I Contents II List of tables IV List of figures V Abbreviations VI Abstract VII 1 Introduction 10 1.1 Global extent of alcohol use 10 1.2 Alcohol-attributable disease burden 11 1.3 Estimating the alcohol-attributable burden 12 1.4 Cardiomyopathy 18 1.5 Alcohol and cardiomyopathy 19 2 Aims and objectives 21 3 Study design and methodology 21 3.1 Study design 21 3.2 Data sources 22 4 Study I - Quantifying the global contribution of alcohol consumption to cardiomyopathy 25 4.1 Background 26 4.2 Methods 27 4.3 Results 32 4.4 Discussion 38 4.5 Conclusion 41 5 Study II - National, regional and global mortality due to alcoholic cardiomyopathy in 2015 42 5.1 Introduction 43 5.2 Methods 44 5.3 Results 45 5.4 Discussion 51 6 Study III - Mortality from alcoholic cardiomyopathy: Exploring the gap between estimated and civil registry data 57 6.1 Introduction 58 6.2 Experimental section 59 6.3 Results 62 6.4 Discussion 67 7 General discussion 72 7.1 Summary of the findings 72 7.2 Strengths and limitations 72 7.3 Implications for future research 75 7.4 Implications for alcohol policy 79 7.5 Outlook 80 7.6 Conclusion 81 8 References 83 9 Appendix A (study I) 97 10 Appendix B (study II) 99 10.1 Methods 99 10.2 Results 103 11 Appendix C (study III) 119 11.1 Methods 119 11.2 Results 124 12 Erklärung gemäß § 5 der Promotionsordnung 128