Pelvic Floor Dysfunction: (PFD) encompasses symptoms that rarely occur in isolation and include urinary and faecal incontinence, rectal evacuatory dysfunction and pelvic organ prolapse. It impacts on the quality of life of at least one third of adult women, with recent reviews suggesting that pelvic floor prolapse may occur in up to 50% of parous women. PFD is associated with a delay in seeking help. Why women with PFD seek or do not seek help for their symptoms has been unclear but is recognised as being multi-factorial. Aim: to learn from women with PFD, to understand the coping mechanisms they develop to live with PFD, and the triggers which prompt their seeking help. Methodology: this study, grounded in the naturalist paradigm, was a micro-ethnographic study focusing on the emic perspective of a defined group, women diagnosed with PFD, who presented to an East London Hospital for treatment. Leininger?s Culture Care theory and ethno-nursing methods were used to facilitate knowledge generation. The study took place in three consecutive phases, each informing the next phase. Phase 1 - One Life Health Care History. This was an instrumental case study which obtained a personalised and longitudinal account of the woman?s health, care and illness experiences from a lifetime perspective. Phase 2 - Eight semi structured interviews; these focussed on the themes generated from a review of the literature pertaining to coping and help seeking behaviour, and themes generated from Phase 1, which were continued until saturation was achieved. Phase 3 - Focus groups from three cultures (Turkish, Orthodox Jewish and African) which represent the ethnic mix of the local population. These explored universality and diversity amongst different cultural groups with respect to coping and help seeking behaviour. Results: this study has identified universality and diversity in coping and help seeking behaviour in women with PFD. Personality and culture have a significant impact on coping and help seeking behaviour, and lack of knowledge is a barrier to help seeking. Social taboo and the role of women in society influenced the coping behaviours of women. Women developed masking and containment strategies, and avoided aspects of social interaction to ensure their PFD problems remained secret. The fear of disgrace (opprobrium) and the delay in seeking help is linked to the woman?s position in her society, and the degree to which women appropriate opprobrium is dependent on their personality and their cultural feelings of self-worth as women in their own communities. Recommendations: if women are to be encouraged and supported to seek help for their PFD, it will be imperative to raise public knowledge and awareness of PFD. Public Health Departments, in conjunction with GP practises, will be key in promoting awareness and advertising integrated PFD services, ensuring posters and information leaflets are translated and displayed in facilities frequently used by women. Facilitating ease of access to PFD services will require the development of integrated PFD services, with community based self referral clinics or drop-in clinics being made available. Health care providers need education and support to ensure they empower women to seek help by giving them permission to discuss any PFD concerns they may have. Conclusions: the contribution to knowledge from this study include the lay care practices that women with PFD employ in order to cope with the problem, and an appreciation of the laycare practices utilised by women. Understanding of care influencers has facilitated recommendations for service and practice development. Areas for further research have been identified. The increasing prevalence of PFD is well known, with studies suggesting that over the next 30 years the number of women seeking help for PFD symptoms will increase at twice the population growth rate. Knowledge and understanding of women?s coping and help seeking behaviour is essential if services are to be developed to meet this growing need. Knowledge generated from this research in relation to opprobrium appropriation makes a unique contribution to the discipline of nursing.

The overall aim of the research described in this thesis was to investigate the basic mechanisms of the pupil of the eye in relation to human vision and brain function. It also evaluates the potential application of new research techniques to clinical studies that involve assessment of the visual function. Pupil response components were investigated in normal subjects and in patients with damaged visual pathways. A series of experiments were carried out to investigate the pupil response to periodic modulation of several stimulation parameters such as: luminance contrast, stimulus size, spatial and temporal frequency content, and colour. Much larger responses were found for square-wave as compared to sinusoidal luminance modulation. A model with two populations of neurones (sustained and transient) was developed to explain the non-linear combination of two response components in the light reflex. In contrast to these findings, responses to isoluminant coloured stimuli or sinusoidal gratings whose spatial average luminance is equal to that of the background do not depend of the temporal wave-form of the stimulation. Studies in patients with lesions to specific areas in the brain suggest that these responses are caused by a transient weakening of the steady central sympathetic inhibition to parasympathetic neurones innervating the sphincter muscle as a result of cortical processing of specific stimulus attributes such as colour and spatial structure. Pupil measurements in patients suffering from demyelinating neurological disorders such as multiple sclerosis and optic neuritis also confirm the existence of distinct pupil response components and reveal selective loss to chromatic and luminance pathways. The results indicate a preferential damage to thinner axons which are thought to predominantly mediate the chromatic responses. These studies suggest that the use of modern pupillometric techniques in neuro-ophthalmology can yield useful information on the extent of the damage and the progression of disease in lesions of the optic nerve.

Diabetes mellitus designates a range of metabolic disorders characterised by hyperglycaemia due to deficient or absent insulin secretion, insulin action, or both. In particular, Type 1 diabetes is characterised by a total lack of endogenous insulin secretion which has to be replaced by exogenous insulin to control the plasma glucose concentration. An extracorporeal wearable artificial pancreas (AP) has been a research aim for over three decades. The research is motivated by the need to improve glucose control. Results of a major study, the Diabetes Control and Complications Trial (DCCT), have demonstrated that improvements in glucose control prevent or delay long term complications, which are the main causes of morbidity and mortality in subjects with Type 1 diabetes. Prior to a clinical evaluation, performance of new medical devices can be tested in silico. Such an approach has been adopted extensively by the pharmaceutical industry in the development of new drugs. In silica testing benefits from relatively low financial, human, and time costs by comparison with the resources required for a full clinical evaluation. The aims of the present thesis are to identify components of the AP, integrate them into a simulation environment, and design an in silico evaluation strategy for the development of closed-loop algorithms with the ultimate goal to assess safety and efficacy prior to clinical evaluation. In the present work, submodels of metabolic processes were linked to represent the characteristics of the glucoregulation in Type 1 diabetes. The submodels were associated with sets of parameters to account for variability in population and individual responses to meals and insulin therapy. The model of glucoregulation in Type 1 diabetes was extended by models of subcutaneous (sc) glucose sensing and sc insulin delivery to represent all aspects of the AP. A systematic approach was developed and employed to evaluate, in silica, the potential and limitations of an AP glucose controller. This was exemplified by evaluating a nonlinear model predictive controller. The robustness of the AP was explored by hypothesising various perturbations induced by different system components. A further objective included the establishment of a qualitative grading scheme of glucose control from the clinical viewpoint. This was followed by a comparison between results from simulations and a clinical trial of 24 hours, which gave the proof of concept of in silica testing. It was found that despite discrepancies due to initial conditions and meal differences, the simulations indicated well the outcome of the clinical trial. In conclusion, the thesis demonstrates the significant potential of in silica testing to make predictions about system behaviour aiding the assessment of safety and efficacy of control algorithms during the development of an AP.

Some people with aphasia may have difficulty in talking about events because of trouble in processing situations in a language-ready fashion. A number of models of language production include a level at which messages are shaped to the demands of a particular language system. However, the relation between such conceptual processing and production in aphasia has been less fully explored. This study takes an empirical approach, investigating the relationship between the verb and sentence difficulties of six people with aphasia and their conceptualisation of events. Following a range of preparatory assessments, so individuals were hypothesised to have some difficulty in conceptualising events for language. Three novel tests were then devised to explore the skills of these individuals, and in one case, the whole group, in more detail. One test examines participants' focus over pictured situations, through their naming of the people and objects involved. A second probes the adoption of perspective over a particularly problematic situation type, investigating the effect of visual and linguistic cues on verb production. The third test focuses on gesture, exploring the relationship between verbal description and the production of action gestures. One participant's drawing of simple events was also probed using a recently developed assessment (Sacchett, 2005). In each case the results point to some differences between the participants with aphasia and a group of non-brain damaged speakers, thus providing support for the psychological reality of the notion of 'thinking for speaking' (Slobin, 1996) in aphasia. In addition, the test findings bring to light some previously hidden processing strengths. However, they also highlight the difficulty both of designing valid tests in this area and of accurately interpreting their results. The discussion considers the implications of the findings for therapy in aphasia, and for our understanding of the relationship between language loss and event conceptualisation.

Breast cancer is both the most common cancer and the leading cause of cancer related death among women around the world. The incidence of the disease is generally considered higher among women in the developed countries than the developing countries; however, the mortality rates for women in the developing countries meet or exceed those of the developed world, indicating poorer prognosis (Pannuti et al., 2000; WHO, 2000; IARC, 2001; IARC, 2002; Anderson et al., 2003; Tannerberger et al., 2004). Ghanaian women, like many other women from the developing countries, have a low participation rate in breast cancer screening services. As a result, the disease is commonly diagnosed at late stages leading to a poor outcome with high mortality rates. Efforts toward reducing the mortality from breast cancer should be focused on implementing cost-effective public health strategies to improve early detection and appropriate treatment (Pannuti et al., 2000; WHO, 2000; IARC, 2001; IARC, 2002; Anderson et al., 2003, Tannerberger et al., 2004). The main objective of the study was to assess breast cancer related knowledge, attitudes, beliefs, behaviour and screening practices among Ghanaian women in the study areas. Investigating an issue such as the knowledge, attitude, belief and breast cancer screening practices is of great importance, not only in identifying obstacles to participation in breast screening and treatment, but also to guide the development of future health promotion programmes to improve breast cancer care in Ghana. The study was conducted in two phases, in Accra and Sunyani, both in Ghana. The first phase involved a total of 474 Ghanaian women aged between 40 and 70 years. Data collection was initially accomplished by using researcher-administered questionnaires, designed to obtain relevant socio-demographic characteristics, knowledge, attitudes, beliefs and practices towards breast cancer (Appendix iii pagel69). The questionnaire was pre-tested in a pilot study in Accra on 68 women before the major study. The second phase was accomplished by semi-structured interviews conducted on 10 breast cancer patients, 10 breast clinic attenders, 2 traditional healers and 3 Consultants, involved in breast cancer management in Ghana. Transcripts of the interviews appear in Appendices iv-vii page 178-231). Characteristics of the subjects that participated in the study are covered in the first part of the findings. The majority of the women who participated in the first phase, (49.2%) were between the ages of 40 - 45 years (table 6: 3: 2a page54). With regards to the education of the respondents, it was observed that in sum 85.9% of the respondents (table 6: 3: 3 page57) had received some level of education. On employment, the vast majority of respondents (74.3%) were engaged in the informal sector, 14.2% in the formal sector and 11.5% unemployed.

Nutrition, or malnutrition, is an inescapable facet of human health and disease. Fuelling the human body with calories is essential; a bewildering range of micro and macro-nutrients, vitamins and essential trace elements are also necessary to maintain the physiological milieu; and are implicated in disease states when lacking or present to excess. A perceived awareness of ‘healthy’ nutrition is ubiquitous in modern society; claims made by manufacturers of specific foods or supplements are usually driven by commercial concerns and rarely backed by sound scientific evaluation. Nutritional modification is a highly attractive option to potentially alter health status or reduce the risk of future disease. Vast sums of money are spent by Western Governments on promotion of healthy eating, in an attempt to reduce future spending on pharmacotherapy - usually for type-2 diabetes, cardiovascular disease and other complications of obesity. Improvements in population health and reduced dependency on health-care resources provide major stimuli for this interest in what we consume. Nutrition also plays a central role in the management of many chronic disease states. Dialysis dependent end-stage renal failure may be one of the most extreme examples where adherence to fluid restrictions and dietary regulation of potassium and phosphate can make the difference between a swift demise on dialysis and survival to renal transplantation. Other chronic conditions are being increasingly recognised as having nutritional components, particular in the field of respiratory medicine. This thesis examines two different approaches to nutritional intervention in subjects healthy but at risk of future disease, and in those already burdened by a chronic disease state. Part A involves patients with Chronic Obstructive Pulmonary Disease (COPD), and evaluates creatine, an ergogenic aid used in athletes to improve performance. Low body mass index is common in COPD and heralds a poor prognosis. Further evaluation of body composition reveals significant losses of skeletal muscle mass in COPD and this is likely to play a major role in the progression of disease. There is some evidence pointing to beneficial effects of creatine on lean body mass creatine in patients with stable COPD. This study assesses creatine in a novel setting, not previously researched. Patients hospitalised with an exacerbation of COPD were recruited to a randomised, double blind, placebo controlled clinical trial and followed up after receiving 2 weeks of nutritional supplementation with either creatine or placebo. Part B involves healthy, overweight subjects, potentially at risk of future cardiovascular disease. This randomised, double blind, placebo controlled clinical trial assessed established risk markers for cardiovascular disease along with novel risk markers. These included novel plasma biomarkers, non-invasive measurements of vascular elasticity using pulse wave tonometry and assessment of cutaneous microvascular and endothelial function using laser doppler iontophoresis. Subjects were randomised to 4 weeks of either a polyphenol rich juice beverage or placebo and were assessed at baseline, mid-point and

Being among the most popular and efficient classification and regression methods currently available, implementations of support vector machines exist in almost every popular programming language. Currently four R packages contain SVM related software. The purpose of this paper is to present and compare these implementations. (author's abstract) / Series: Research Report Series / Department of Statistics and Mathematics

This thesis is concerned with the moments, places, and circumstances in which the great magnitude of the world is felt. I live within the vast space of the spherical earth and the infinite space of the universe, however, it is rare that I consider the immensity of this space in which I live and endeavor to build. This thesis is an examination of the ability of both architecture and landscape to frame immense space and phenomena of the earth, reinforcing our relationship with the larger space that we inhabit. This work is rooted in two accounts of immensity: The first is a landscape, a beach on the small Danish island of R??m??, where I stood on a vast, flat plane, surrounded by the seemingly limitless extension of space. The second is an architectural space, Kunsten Museum of Modern Art Aalborg in Northern Denmark by Finnish Architect Alvar Aalto. There I stood in an interior that framed an experience of immensity unnoticed from the exterior. The beach was for me a rare and profound experience of immense space, and the museum an architectural examination of immensity mediated by mass and interiority. I weigh these personal accounts against immensity portrayed in art, architecture, fiction, and philosophy. I consider paintings by German Romantic painter Caspar David Friedrich, an Infinity Environment installation by contemporary artist Doug Wheeler, and the documentation of sand-filled homes in Namibia by contemporary photographers Y?? Ogata and Ichir?? Ogata Ono. I examine the portrayal of immensity in Michael Ondaatje???s novel The English Patient and Karen Blixen???s short story Babette???s Feast and consider how immensity is manifest in space, people, and architecture in the writing of philosophers and theorists Dom Hans Van der Laan, Emmanuel Levinas, and Otto Friedrich Bollnow. Lastly, I consider the role that architecture plays in framing immensity by analyzing Kunsten Museum of Modern Art Aalborg and Grundtvig Church in Copenhagen by Danish architect Peder Vilhelm Jensen-Klint alongside Henry Plummer???s writing on the Salk Institute and Kimbell Art Museum by American architect Louis Kahn.

The vasodilator response to acetylcholine (ACh) was investigated in the hypobaric chronic hypoxic rat model of secondary PHT. The maximum vasodilator response to ACh was significantly increased in the PRAs of chronic hypoxic rats when compared to normoxic control rats. The presence of hypoxia-induced PHT influenced the mediator profile responsible for the ACh-induced vasodilatation. In control rat PRAs, the ACh-induced vasodilator response appears to be mediated by endothelium-derived hyperpolarising factor (EDHF) via small and large Ca2+-activated K+ channels (SKCa and BKCa, respectively). In chronic hypoxic rat PRAs, the ACh-induced vasodilatation was mediated by nitric oxide (NO), prostacyclin (PGI2), and EDHF. However, the involvement of EDHF in the ACh-induced vasodilator response requires confirmation through the use of electrophysiology. The novel vasoconstrictor peptide human urotensin-II (hU-II) was shown to only elicit vasoconstriction in 30% of humans PRAs in the presence of the NO synthase (NOS) inhibitor, L-NAME. However, hU-II was revealed as a vasodilator of human pulmonary and systematic resistance arteries (SRAs) which was equipotent with another potent endogenous vasodilator peptide, adrenomedullin. The hU-II-induced vasodilatation was shown to be mediated by PGI2 and EDHF via BKCa and SKCa channels. Again, the involvement of EDHF in the hU-II-induced vasodilator response awaits confirmation through electrophysiological studies. The in vivo and in vitro response to endothelin-1 (ET-1) was investigated in the PRAs of patients with different severities of left ventricular dysfunction (LVD), using PRAs from patients undergoing lung resection for bronchial carcinoma as controls. The LVD patients groups were classified according to their ejection fraction, as assessed by echocardiographic assessment. The patients were divided into the following groups: an ejection fraction (EF) of >40% = good LVD; an EF of 30-40% = moderate LVD; and an EF of <30% = poor LVD. The in vivo experiments (which were not conducted by myself) showed a significant increase in the baseline measurement of pulmonary vascular resistance (PVR) between the good and poor groups, demonstrating the development of PHT as a consequence of severe LVD. The in vitro experiments revealed no significant increase in the potency of, or maximum contractile response to, ET-1 as the severity of LVD progressed.

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