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Generally, most of the in vitro tests used in neurotoxicology are limited to transformed cell lines which are derived from rodent or human. For an in vitro test to have high rate of predictability of neurotoxicity and teratogenicity it should undergo the important processes of embryological development, such as cell proliferation, cell migration, and differentiation. Human neural stem cells have been proposed for this purpose, which have the ability to divide, differentiate, and migrate. In this study, it was found that double coating of laminin with either poly D lysine or poly L lysine was most suitable for growing human neural stem cells rather than coating with a single extracellular molecule. Several chemicals and drugs were then chosen to assess the utility of neural stem cells as an assay for neurotoxicity: methyl mercury and lead acetate; four anti-epileptics drugs (sodium valproate, phenytoin, carbamazepine, and phenobarbitone); anti-oxidants (folic acid and melatonin). These anti-oxidants were tested alone and when added to sodium valproate and to phenytoin (which are well known in their teratogenicity), and other drugs (lithium, diazepam, and amitriptyline), which are weak teratogens. To assess the effects of these molecules on human neural stem cells cell survival, total cellular protein, neuronal process length, neurosphere sizes, migration distance, Glial Fibrillary Acidic Protein, and tubulin III protein expression were measured. The study shows that methyl mercury caused significant reduction in most of the end points from the dose of 1µM and it led to significant increase in Glial Fibrillary Acidic Protein expression (which is a sign of reactive gliosis). Lead acetate led to a significant reduction in cell migration 48hours after treatment with 10µM. In the case of the anti-epileptics, sodium valproate appeared to reduce neurosphere size significantly from the dose of 500µM and decrease migration distance significantly 48hours after treatment with 1000µM. Moreover, phenytoin treatment resulted in significant reduction in neurosphere sizes from the dose of 25µM and reduced cell migration significantly from the dose of 50µM. However, the other anti-epileptics (carbamazepine and phenobarbitone) revealed their effect only at high doses which are above their therapeutic range. On the other hand, adding the anti-oxidants (Folic acid or Melatonin) to sodium valproate or phenytoin had to some extent beneficial effects, by making their toxic effect appear at doses which were higher than when used alone. Regarding the other drugs (lithium, diazepam, and amitriptyline), it seems that their toxic effect appeared only at doses which are higher than the therapeutic range. Therefore, it can be concluded that human neural stem cells are a sensitive model in detecting the neurotoxicity of methyl mercury and lead acetate at low doses and can predict the neurotoxicity of sodium valproate and phenytoin at their therapeutic doses.

The aim of this research has been the examination of the long term psychological consequences of admission to the Intensive Care Unit (ICU) for critical illness. The major objectives were first, psychometric assessment at specified intervals post-discharge, using the General Health Questionnaire, Rosenberg Self Esteem scale, and the Impact of Event Scale, and secondly identification of ICU related variables which influence psychological wellbeing and recovery. The design was prospective and used survey methods. Seventy-two patients were recruited from the ICU at St James's University Hospital in Leeds. Data were collected at six weeks, six months and twelve months post-discharge. The initial analysis produced evidence of discrimination between subgroups, in particular age, length of stay in ICU, admission severity, indication for admission, communication, pre-existence of cancer, and the use of muscle relaxant drugs. Further analysis by way of a logistic regression identified four factors which may have predictive properties - age, admission severity, trauma and pre-existence of cancer. Patients from younger age groups reported more post traumatic stress symptoms than older patients; patients with pre-existing cancer also reported fewer post traumatic stress symptoms. Patients admitted following trauma reported poorer psychological outcome. Admission severity was negatively associated with psychological dysfunction, with those who were sickest on admission reporting fewer problems. Symptoms of post traumatic stress disorder were found in a number of patients; at final follow-up 27% of the surviving sample had medium levels, and 27% high levels of post traumatic stress symptoms. ICU patients form a fragile group to study and sample attrition was considerable. Nevertheless the findings are of interest to this developing research area and suggestions are made regarding their utilisation.

Countries around the world provide various forms of legal recognition for same-sex relationships. In the UK, legal recognition for same-sex relationships first became available in 2005 with the introduction of civil partnership (CP) which remained the only option until 2014 when same-sex civil marriage legislation was passed in England, Wales and Scotland. In a context of heated debate and speculation, this thesis contributes to emerging literature on individual’s experiences of legal forms of same-sex relationship recognition by exploring how CP is experienced, given meaning, and situated biographically. The thesis draws on personal narratives elicited through qualitative life story interviews with 28 men from across the UK. Interviews covered the life course, but were thematically focused around CP to provide insight into: motivations for entering CPs; experiences of planning, constructing, and participating in CP ceremonies and celebrations; and meanings and impacts of becoming and being civilly partnered. The resulting co-constructed narratives were systematically analysed using narrative methods. Minority stress theory, along with other relevant theories and concepts, were employed to further illuminate, analyse, and interpret participants’ narratives. Two generational core-narratives were identified in participants’ biographical accounts. Older participants told stories of struggle and resilience, and younger participants told new narratives of normality. Despite some generational differences, all participants reported experiences consistent with minority stress, including coping and resilience mechanisms, arising from their gay social identities which remain subject to residual stigma. Participants’ accounts of CP revealed that becoming and being civilly partnered was largely, but not wholly, a positive experience which can be understood in terms of the overarching, and overlapping themes of citizenship, normativity and well-being. With regard to citizenship, participants welcomed the legal rights and recognition of CP which was seen to offer varying forms and degrees of equality. In terms of normativity, some participants reported that CP confirmed their perceived normality while others thought it was a normalizing process granting them normative identities. Furthermore, while some engaged in, or were compelled to engage in, arguably normative marital practices, others felt they were resisting these. Regarding well-being, becoming and being civilly partnered seemed to mitigate minority stress and contribute to well-being. Overall, the knowledge generated from the personal narratives presented in this thesis enriches debates, contributes broadly to the social sciences literature, and provides new perspectives on, and representations of, gay men’s identities, lives, and relationships.

Background: Mortality rates have fallen resulting in people living longer with cancer. However, cancer survivors can face significant treatment related physical and psychosocial issues including comorbidities. Treatment related side effects can persist in the long-term or may occur many years later. There is now a focus on the best way to provide appropriate care to people who have survived cancer and its treatment. Aim: The aim of this study is to explore the appropriate balance of cancer care for patients following diagnosis and treatment between specialist and primary care. Methods: Semi-structured interviews with a purposive sample of 40 oncologists, CNSs and GPs across Scotland. Data are analysed in a systematic fashion using constant comparison. Findings: Many patients face significant health care issues after a diagnosis of cancer. Professionals often play a pivotal role during follow-up by identifying and managing patients’ physical and psychosocial needs and by sign posting to address the challenges that arise. Psychosocial needs, long-term and late effects are sometimes not addressed. Oncologists are leaders of the cancer care process. CNSs often play a central role in survivorship both in specialist and primary care. GPs’ roles are seen to span the full spectrum of survivorship care, although this is largely opportunistic in nature. Communication between specialist and primary care is a key issue. Professionals perceived that there is insufficient contact across the interface in terms of understanding others’ viewpoints about the nature of their work. Efforts are needed to improve the timeliness and detail of letters to primary care. Successful primary care follow-up may require development of nurses’ roles in general practice and the community. It is perceived that GPs could attend specialist care for survivorship education or become cancer specialists in general practice. Cancer Care Reviews are considered useful tools in terms of allowing GPs to engage with their patients. Improvements to technology and further research are considered central to optimal cancer care. Conclusion: Considerable barriers exist with the current system of follow-up. After the treatment phase, GP survivorship care is largely opportunistic and driven by patients’ needs. Based on the findings from this study, strategies of care could potentially be planned to facilitate the role of primary care. However, research supporting these practices is needed.

Background: Obesity is a global problem that resulted from excessive positive energy balance. Decreased physical activity and other dietary, environmental and genetic factors all contribute to its development (Han et al., 2010). On a larger scope, social, economic and cultural factors also predisposed to its occurrence globally (WHO, 2000). Of particular concern is the rise in paediatric obesity with subsequent rise in morbidity during childhood, adolescence and young adulthood, and rise in morbidity in adulthood, including adult obesity, as well as increased risk of premature mortality in adulthood (Reilly and Kelly, 2011, Reilly, 2006). In Kuwait, paediatric obesity prevalence is high and may be continuing to rise in all age groups (Mirmiran et al., 2010, Al-Isa and Thalib, 2008, Al-Isa and Thalib, 2006). Affluence and rapid transformation of Kuwaiti society after the discovery of oil is one theory behind the changes that took place in the dietary and physical activity patterns which could be the main mediators for the obesity epidemic in Kuwait (Ng et al., 2011). However, despite the paediatric obesity problem in Kuwait there is not a widely available treatment solution or attempts to find obesity treatment solutions locally (Al-Isa et al., 2010b). At an international level, effective treatment strategies were traditionally confined to the Western world, particularly the Epstein group in the USA (Epstein et al., 2012, Oude Luttikhuis et al., 2009, Epstein, 1996), though other successful treatment programmes have been published since the early pioneering work of Epstein (Ho et al., 2012). The aim of the thesis was to: a) test the hypothesis that obesity impairs health related quality of life in Kuwaiti adolescents and test the differences in health related quality of life assessed by self-report and parent-proxy report, b) determine the prevalence of cardiometabolic risk factor abnormalities and metabolic syndrome in a sample of obese Kuwaiti adolescents, and c) test the effectiveness of a treatment intervention for adolescent obesity and compare it to a primary care control. Methodology: Chapter 4 describes the health related quality of life study (HRQL) that was conducted at baseline comparing the HRQL between obese and healthy-weight Kuwaiti adolescents (aged 10 to 14 years). Five hundred eligible consenting participants were assessed using the Peds QL™ self-reports as well as 374 parent-proxy reports. From the obese group (n= 224), 82 participants agreed to participate in the National Adolescent Treatment Trial for obesity (NATTO) (chapter 6), an assessor-blinded randomised controlled trial, and were randomised to the intervention programme or primary care control over 6 months. The intervention programme aimed to change sedentary behaviour, diet and physical activity in low intensity doses through 6 hours contact over 24 weeks. At baseline, 80 blood samples were collected from 80 out of the 82 participants from the NATTO study, for the assessment of cardiometabolic risk factors namely C-reactive protein, intracellular adhesion molecules, interleukin-6, fasting blood glucose, fasting insulin, alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, total cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, and adiponectin. Metabolic syndrome was assessed using two criteria modified for use in younger individuals. Results: From the health related quality of life study, obesity was not associated with impaired health related quality of life in regression analysis. In a structured paired comparison of 98 pairs of obese adolescents vs healthy weight peers, impaired health related quality of life reached significance only for the physical quality of life domain (obese group score = 87.5, healthy weight group score = 93.7, 95% CI for quality of life score = -1.5, -9.4, p 0.007). In a paired comparison between parent-proxy vs self-reports for the obese adolescents, physical quality of life score (parent-proxy score 81.3, self-report score 87.5, 95% CI = -3.2, -11.0, p < 0.001), psychosocial score (parent-proxy score 76.7, self-report score 85.0, 95% CI = -4.2, -10.8, p < 0.001) and total score (parent-proxy score 78.8, self-report score 84.8, 95% CI = -4.9, -10.9, p < 0.001) were all significantly lower in the parent reports. The cardiometabolic risk factors with highest prevalence of abnormal values in the sample (n = 80), described in chapter 5, were; aspartate aminotransferase (89% of samples abnormal), insulin resistance by homeostasis model assessment (HOMA) (67% abnormal ), intracellular adhesion molecule (ICAM) (67% abnormal), fasting insulin (43.5%), C-reactive protein (42.5%), low density lipoprotein (LDL) (35%), total cholesterol (34% abnormal), and systolic blood pressure (30% abnormal). Of all participants (n=80), 77 had at least one impaired cardiometabolic risk factor besides their obesity. Prevalence of Metabolic syndrome was 21.3% using the International Diabetes Federation definition and 30% using the Third Adult Treatment Panel definition. At 6 months outcome in the treatment intervention NATTO, the trial had acceptable retention (n =31 from the intervention group and n =32 from the control group), but engagement with both the intervention and control treatment (as measured by attendance at treatment sessions) was poor. The intervention had no significant effect on BMI Z score relative to control, and no other significant effects of the intervention were observed. Conclusion: In a sample of obese Kuwaiti adolescents, obesity was not associated with marked impairment of health related quality of life; however, marked impairment in multiple cardiometabolic risk factors was present. Conducting the National Adolescent Treatment Trial for Obesity in Kuwait was feasible but not efficacious, and future obesity treatment trials should incorporate a qualitative assessment for better participants’ engagement.

Over the past decade there has been mounting evidence of the significant role played by the myriad attributes of our city's built environments in shaping our health and well-being. This thesis hypothesizes that the constituent components of the built environment, especially the configuration and design of land uses and street networks governs the distribution of resources and services, configures the neighbourhood activity space, and thereby influences individual physical activity behaviours, social interactions, weight outcomes as well as mental health and well being. Enhanced accessibility to health-promoting community resources improves local opportunities for physical activity, thereby enhancing mobility, social interactions and independence as well as reducing isolation. The first section of this thesis conceptualizes the urban health niche as a novel holistic and spatially-explicit paradigm in public health and proposes a health niche model of healthy city. Based on the proposed paradigm and gathered research evidence, multilevel data sets pertaining to health, socio-economic, built and natural environment have been produced and integrated together to constitute the high resolution database, spatial Design Network Analysis for Urban Health (sDNA-UH). sDNA-UH has been developed for the assembly constituency of Caerphilly, South Wales enabling operationalization of the spatial elements of the proposed urban health niche. State-of-the-art spatial and network analysis techniques have been employed upon the UK Ordnance Survey Mastermap data layers to quantify the various facets of urban built environment in the form of built environment morphological metrics (morphometrics) with the potential to influence individual's health. Based on the developed sDNA-UH, a series of three empirical studies comprising multilevel cross-sectional and longitudinal models have been presented which examine the association between specific attributes of a built environment and health outcomes. Firstly, a two-part multi-level regression model was employed to examine the impact of built environment configuration upon psychological distress. Land use mix, density of amenities, local street-network general accessibility (‘betweenness’) and slope variability were identified as significant predictors. Secondly, the first long-term longitudinal evidence relating the built environment to change in obesity in older people identified land use mix, density of amenities street network accessibility and slope variability as significant predictors. The third study examined the health effects of differential accessibility of an individual's dwelling with respect to multiple service and facility catchments at multiple spatial scales. Dwelling level density, dwelling type, density of community services, street network movement potential expressed in terms of betweenness index as well as neighbourhood-level deprivation were identified as the significant parameters. The study reported significant differences in point estimates and level of significance when comparing the two spatial scales of 0.5 and 1.0 mile street network catchments. The empirical evidence thus generated lends support to the thesis’ principal hypothesis that the built environment influences individual health behaviour and eventually health. The research concludes that optimized design and planning of urban built environments act as effective public health intervention in our goal of health-sustaining communities and a healthy city.

This thesis is based on a mixed methods study with a sequential exploratory design, and is about the fertility preferences of women living in rural South Africa. The quantitative secondary analysis utilises the South African Demographic and Health Surveys of 1998 and 2003, and the qualitative ethnographic fieldwork was carried out in a rural area of KwaZulu-Natal province, South Africa, in 2011 and 2012. The fieldwork included ethnographic field notes and maps generated through participatory mapping exercises, 63 semi-structured interviews with women of different generations and 6 key informant interviews. The thesis examines women’s landscapes of fertility and focuses on intergenerational understandings of fertility preferences, migration and the HIV/AIDS pandemic. The thesis identified that women’s landscapes of fertility are subject to change over time and differ between women of different generations. Older women’s landscapes of fertility are influenced by understandings of the importance of continuity of family whilst those of younger women are synonymous with their experiences of increasing autonomy and agency, caused by escalating modernity. For younger women, migration was a key issue within their landscapes of fertility and their migration later affected their mothers who became migratory followers of their daughters. This is a reversal of typical paradigms of migration, as it identifies that women from different generations can be migratory followers or leaders. It was found that HIV influenced women’s landscapes of fertility due in part to the South African, changing socio-political responses to the disease. The thesis contributes to geographical and anthropological understandings about change in women’s fertility preferences over time in the context of societal change. The thesis also identifies the value of ethnographically informed understandings of fertility preferences as a key indicator of demographic change and population shifts.

This Thesis is concerned with the history of health care and medicine in the State of Qatar. I have traced its evolution from the first man, through to the presence of Islam until oil was discovered in 1939. I then continued with close personal interest to follow the development of health and medicine in the more recent "post-oil discovery" years, in particular the last decade when Qatar matches its health and medical care with the pre-eminent services of the Arabian Gulf region (Gulf Co-operation States) and the world. The historical, cultural and political events that influenced development in the Arabian Peninsula have been many and varied causing intriguing shifts in the evolution of health practice in medicine. Traditional medicine traversed the trade routes, Islamic medical practices became firmly rooted in the Arabian Peninsula and oil wealth in the latter years empowered the Gulf States as significant buyers of modern medical technology and manpower. This thesis is organised in logical sequence with early chapters concentrating on primitive, ancient history and the pre-Islamic period. Relevant anthropological, archaeological, cultural and historical information has been outlined and analysed in the early chapters, in an attempt to identify the significant influences on the health and medical practices of the times. Plausible theories and conclusions were sought on health practices and medicine; however, a dearth of factual information necessitated some speculation on how tribal medicine and health practices were derived and disseminated throughout the region. Less speculation was necessary for the Islamic era. Islam was widespread with the daily lives and cultural practices of Muslims strictly controlled; particularly in terms of morality, marriage, dress, health and hygiene. Certain chapters describe the significant contribution of Islamic medicine to the development of medicine in general and review the impact of Islam on health practices within the Muslim society of the Arabian Peninsula including Qatar. The Arabs themselves had a profound effect on the medicine of the world, with their translations from Greek to Arabic and other languages. The remaining chapters look closely at contemporary Arab society in Qatar, from the discovery of oil to the present day.

Sexual health matters! This motif underpins the entire thesis. With survey responses from university educators and focus group encounters with clinical professionals undertaking the UK-wide Sexual Health Skills course, the study explores ways in which specific discourses pertaining to sexual health and illness inform the need for, and provision of, professional education for nurses in England. Through using a Foucauldian ‘lens’ and a novel process called crystallisation in sexualities and gender epistemologies (S&GE), it was possible to shed new light on some old problems hindering nurse education. The methodologies facilitated a discursive engagement between the power / knowledge of sexual health sciences (scientia sexualis), the orthodox ‘regimes of truth’, and various silenced voices. The silenced voices pertain to wider, socially and clinically ‘invisibilised’, needs of clients or patients in relation to the provision of nurse education. Set against the backdrop of England's first ever Government strategies on teenage pregnancy, sexual health and HIV, statistics on narrow definitions of sexual ill-health are still considered the worst in western Europe. Nurses acknowledge these poor facts, and witness to additional neglect related to sexual well-being in the wider, holistic, domains of a person's life, health and relationships. Respondents recount a lack of formal sexual health education in pre- and post qualifying curricula, including incidents of critical, experiential, ‘on the job’, learning which are capped and thwarted by clinical and educational staff who are unable and / or unwilling to explore the full learning potential through reflection and analysis of practice. Respondents acknowledge how their professional education frequently ill-equips them to deal with requirements in practice as well as newer, public health, demands on their roles to increase preventative education and effective health promotion. This thesis gives them a voice in expressing such concerns. The outcome of this work has led to the conceptualisation of a model of ‘learning for life’ across a curricular triptych for professional education which supports client care. Panels of this triptych relate to the foundational or holistic dimensions of sexual health matters; ancillary aspects secondary to other health conditions, and finally, the specifics, those formally defined in epidemiology and strategies of sexual ill-health and associated stigmas. Whether someone qualified twenty-five years ago or within the last three months, the quality and quantity of formal sexual health learning across the curricular triptych model remains negligible and incommensurate with clinical demands on professional nursing care.