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In vitro models are the pillars of fundamental research and drug discovery, offering reductionist methods to better understand cellular responses in isolation. Often these methods are oversimplified, which makes their relevance to human biology and clinical translation ambiguous. Living myocardial slices (LMSLMSs) are viable thin (200-400μm) cardiac tissue slices, with preserved native multicellularity, architecture, mechanical and electrophysiological responses. Recent development in their culture, by us and others, paved the way for long-term preservation of adult mammalian heart tissue in vitro, without significant changes in its function and structure. This model has been extensively used in healthy tissue; however, to date, there are no established pathological models to study disease progression in vitro. Here we hypothesised that LMSLMSs can be used as an informative in vitro disease model to study temporal and spatial changes in cardiac function/structure in response to local cardiac damage. Before inducing cardiac damage, we further improved and characterised the cultured LMS model by designing robust tissue holders, optimising the oxygenation of the media, and establishing the best slice thickness (300μ) for oxygen diffusion and tissue stability in culture. We found that the LMSLMSs were adequately oxygenated in the inner layers and responded to mechanical stimuli with an increase in their contraction and hyperpolarisation of the mitochondrial membrane. We then developed a cryoinjury model, by applying a cooled probe on the LMSLMSs. We found that injury created a distinct necrotic area, surrounded by a border zone (BZ). The injury resulted in preserved force but electrical instability, with the presence of spontaneous contractions. Microscopic analysis of the BZ showed the presence of high numbers of spontaneous Ca2+ sparks, which could be affected by inhibiting the activation of Ca2+/calmodulin-dependent protein kinase II (CamKII). The inhibitory effect was more pronounced in endocardial LMSLMSs, showing transmural differences of CamKII under pathological conditions. Structural analysis of the BZ also showed an acute increase of the sarcomere length and loss of t-tubule density upon culture, that could also account for the arrhythmogenicity of the injured LMSLMSs. One application of therapeutic interventions on the model, by using extracellular vesicles (EVs), did not show any functional or molecular improvements. This thesis demonstrates the significance of using diseased LMSLMSs to study the way that local injury affects tissue stability, function, and structure. Further work is required to better understand the link between spontaneous Ca2+ and contraction events, as well as finding successful therapeutic interventions.

Background: Mental health services in the era following deinstitutionalisation have strongly followed a social support framework of intervention; thereby attempting to increase social connections and support for people with mental health challenges (MHCs). This shift in mental health care provision led to the establishment of statutory community mental health services, but such services do not fully address the needs of people with MHCs who are in their communities. Therefore, with the unavailability and inadequate statutory community mental health services came several barriers for people with MHCs who were unable (or unwilling) to access these formal services. Nevertheless, there are informal community mental health services, such as: (a) faith communities, (b) clubhouses, (c) user-led organisations, (d) day centres and (e) mental health cafés, that may or may not receive funding from the government. However, these providers offer social facilities where people with (MHCs) can socialise, interact, and participate in activities, including employment, learning and creative activities. Methods: This is a constructivist and interpretivist ethnographic study that seeks to understand what The Dragon Café is, as well as to establish the relationships between the place, people and participation in the café. The researcher has used visual and textual data collection methods, including a 3-dimensional video, a floor plan, photographs, fieldnotes from observation and informal conversations, semi-structured interviews, a reflective diary and memoing in order to gather information. Findings: There were five key original findings from this study, not evident in previous literature, and as such, these data fill a gap in knowledge and provide important contributions to the empirical literature. First, the café in this study differs from other informal community mental health services established for specific populations based on diagnosis, work or activity only. The Dragon Café provides a space primarily for socialisation and reducing feelings of loneliness and isolation among those who attend. Second, this study offers an original and detailed ethnographic description of the outdoor and indoor physical environment of a mental health café, using visual and textual data to provide a footprint of the research setting, activities and people in a way that has not been documented previously. Moreover, it provides empirically substantive information on the mental health café in this study, which can be used for future comparative research of informal community mental health services in general and mental health cafés in particular. Third, this study provides the first narratives and experiences of the loss of the place, people (friendships) and participation (activities) among people with mental health challenges who attend a mental health café. They were obliged to deal with several difficult issues following the closure and reconfiguration of the mental health day centres in the UK they were attending. Fourth, this study contributes to the academic field by providing detailed information about how free access and participation in a mental health café offers participants more choice, without the structured and compulsory participation criteria common in other informal community mental health services such as Recovery Colleges. Notwithstanding the perception of choice among the participants, this study is unique in that it is the first to alert us to the differences in power and authority between the patrons and management in a mental health café; and in particular, how this dissonance determines attendees' behaviour and actions. Fifth, this study developed a novel conceptual model which established that relationships between place, people and participation in a mental health café are intertwined; each of these are connected in the interaction under study. The development of a conceptual model is not an effort to produce a discourse on space, but rather a thick description (Geertz, 1973) of the actual outdoor and indoor spaces of the crypt where The Dragon Café is located to assist in identifying the ways that the interactive modalities of place, people and participation, identified by observations and participants' narratives, can contribute to understanding, and potentially developing, informal CMHS in general and mental health cafés in particular. By applying such a theoretical model, we can gain a greater sense of how elements of the whole environment under study are co-dependent and influence our understanding of what makes people with mental health challenges attend informal CMHS in general and The Dragon Café in particular. Discussion: Mental health cafés are situated in the culture of informal community mental health services and align with the mainstream notion of public spaces, where people meet to socialise with others, while at the same time offering a particular and unique set of resources and social activities. This study found that The Dragon Café offers a more diverse and enriched environment for social engagement and connection than is available from the more basic informal community mental health services or drop-in centres. Conclusions: Mental health cafés, such as The Dragon Café draw on the two cultures of mainstream cafés and informal community mental health services to provide a more enriched environment for patrons with MHCs to become involved in a space fostering social engagement and connection. In particular, the Dragon Café avoids the more structured and compulsory participation requirements of informal community mental health services. The less formal and more egalitarian approach of The Dragon Café resulted in high demand for its environment, resulting at times in overcrowding. This unintended consequence of its popularity, in turn, compromised the quality of social integration for those who attended. Recommendations: This study argues for more research into the issue of authority and power dynamics in mental health cafés, together with an exploration of the factors that hinder or enable community integration for people with MHCs. In terms of methodology, this study recommends more ethnographic research using visual and textual data collection methods, in order to add to the limited research activity that has focused on: (a) mental health cafés, (b) informal community mental health services and (c) Recovery Colleges. Furthermore, it is suggested that quantitative studies should be employed to measure the cost-effectiveness of mental health cafés when compared to other mental health services, such as hospital admissions. Practically, this study argues for the revalidation of the UK tertiary institutions mental health curricula to include the issue of informal community mental health services during training, lectures and placements. Also, this study suggests that future research should, at least theoretically, consider the use of socio-ecological model to explore factors that influence community integration for people with mental health challenges. The novel conceptual mode should be used alongside the detailed ethnographic descriptions of the outdoor and indoor physical environment for the future development and reconfiguration of informal community mental health services. In terms of treatment options and policy, this study suggests the re-evaluation of the National Institute for Health and Clinical Excellence (NICE) guidelines, so that the guidelines include informal community mental services as treatment options; thereby addressing people with MHCs, rather than psychiatric conditions.

In this dissertation the waste incineration process has been described, an overview of the state of the art control methodologies given and a new approach, based on input/output linearization and extremum seeking has been presented. This approach has been tested on a model appositely designed. The results have shown that it is possible to control the waste bed temperature to certain reference values, with robustness against changes in the waste composition. It is furthermore possible to identify reference values for the waste bed temperature such as the steam ow rate is maximized, while at the same time fulfilling operational constraints.

The main purpose of the study was to determine selected aspects of the small business food service operators' perceptions regarding the need for training adult food service workers in the Altonna area of Pennsylvania. Information was gathered to help determine the operators' perceptions of the type of training, training site, and their commitment ofmoney and time. Questionnaires were sent to all food service operators who were not members of a chain food service organization. Two follow-up letters, and a selective telephone follow-up resulted in a 31% return, which did not demonstrate an avid interest for a food service training program. The respondents who were favorable toward further training were characterized by a larger yearly volume of business. Respondents supported the idea of utilizing the Altoona Area Vocational-Technical School facilities for inservice training. Promotional considerations for potential food service clientele also are explored: in-house training programs for small food service business operators; interaction of the Cooperative Extension Service home economist, the home economics departments in high schools, and the city sanitarian; service clubs; voluntary community youth groups; high school clubs or organizations; and the feasibility of licensure of food service workers. A bibliography is appended. (EA)

This study is concerned with the plastic buckling of relatively thick tubes and the ensuing succession of instabilities leading to their failure. The first instability is uniform axisymmetric wrinkling that is treated as a plastic bifurcation. As the wrinkles grow, the axial rigidity of the shell is gradually reduced. This eventually leads to a limit load instability beyond which failure in the form of localized deformation takes place. The problem is studied using experiments and analyses. Stainless steel specimens with D/t of 23-52 were custom-designed to avoid stress concentrations and reproduce long uniform pipe conditions. The specimens were compressed to failure under displacement control. In all cases, a second bifurcation involving nonaxisymmetric mode of deformation preceded the limit load. The bifurcation into axisymmetric wrinkling was determined by monitoring the development of wrinkles on the surface of the tubes. This critical state was successfully predicted using an anisotropic deformation theory of plasticity. The anisotropy of the material was established experimentally and modeled using Hill's quadratic anisotropic yield criterion. The problem was first modeled as uniform axisymmetric wrinkling. The model uses Sanders’ shell kinematics assuming small strains and moderately small rotations and includes a modified flow theory of plasticity to accommodate the anisotropy observed in the tubes. Small axisymmetric imperfections based on the critical halfwavelength were integrated into the model. The problem was formulated through the principle of virtual work and solved using Newton’s method. The solution correctly simulates the growth of wrinkles resulting in a limit load instability. The model included second bifurcation calculations from axisymmetric to non-axisymmetric configuration. Second bifurcation instabilities were found to occur before the limit load developed. For this reason, a second model was developed in which non-axisymmetric deformation of the shell was simulated by introducing both axisymmetric and nonaxisymmetric imperfections. Non-axisymmetric responses were found to be highly sensitive to the imperfections. Each experiment was first reproduced accurately by choosing the right combination of imperfections. However, to achieve a satisfactory prediction of the limit state over the whole range of D/t, a thorough parametric study of the imperfection sensitivity was performed. The relative amplitude of the axisymmetric imperfection to the non-axisymmetric imperfection was found to define whether the shell deforms axisymmetrically or not. Furthermore, if one of the imperfections governs the deformation configuration, then the effect of the second onto the response is negligible. Thus, a constant axisymmetric imperfection of 0.05% of the pipe wall thickness and a non-axisymmetric imperfection proportional to (D/t) 2 / m 3 yielded accurate predictions of both mode of deformation and limit load.