Background: Asthma now affects up to 10% of pregnant women in high income countries and international prevalence is rising. It is already one of the commonest chronic diseases that can complicate pregnancy and previous studies have raised concern that women with asthma have increased pregnancy risks. Precise estimates of the magnitude of these risks and the extent to which they may differ by asthma severity and asthma exacerbation rates, have not been determined. Aim: The overall aim of this thesis was to investigate the impact of asthma and asthma therapies on pregnancy and perinatal outcomes in the general female population. Methods: The Health Improvement Network primary care database from the United Kingdom was used to develop a dataset of women matched to their liveborn children and all data on these pregnancies and on pregnancies ending in stillbirth, miscarriage or therapeutic abortion, were extracted for analysis. Three separate studies were carried out using the developed dataset. First, a cohort design was used to compare fertility rates of women with and without asthma or other allergic disease. Secondly, a cross-sectional design was used to compare risks of adverse pregnancy outcomes and obstetric complications in women with and without asthma. Thirdly, a case-control design was used to compare the risk of congenital malformation in children born to women with and without asthma, and to assess whether asthma medications are teratogenic. Results: A study population of 1,059,246 women was obtained and pregnancies ending in 268,601 matched live births, 986 stillbirths, 35,272 miscarriages and 37,118 therapeutic abortions were identified. Women with asthma or other allergic disease had similar fertility rates (live births per 1,000 person-years) to women in the general population. Women with asthma also had a similar risk of pregnancy ending in stillbirth (Odds Ratio (OR)=1.04, 95% confidence interval (CI) 0.86-1.24)) or therapeutic abortion (OR=0.95, 95%CI 0.92-0.99), but had a small relative increase in risk of pregnancy ending in miscarriage (OR=1.10, 95%CI 1.06-1.13), compared with women without asthma. Risks of most obstetric complications were similar in women with and without asthma, regardless of asthma severity or acute exacerbations, with the exception of increased risks of antepartum haemorrhage (OR=1.20, 95%CI 1.08-1.34), postpartum haemorrhage (OR=1.38, 95%CI 1.21-1.57), depression in pregnancy (OR=1.52, 95%CI 1.36-1.69), caesarean section delivery (OR=1.11, 95%CI 1.07-1.16), preterm delivery (OR=1.15, 95%CI 1.06-1.24) and low birth weight (OR=1.18, 95%CI 1.05-1.32) in their offspring. Compared with children born to mothers without asthma, children born to mothers with asthma had a small increased risk of major congenital malformation (OR=1.10, 95%CI 1.01-1.20), however, this was not found for mothers with currently treated asthma (OR=1.06, 95%CI 0.94-1.20). Gestational exposure to asthma medications was safe apart from cromones which may increase the risk of musculoskeletal malformation. Conclusions: These findings indicate that women with asthma do not have substantially increased risks associated with pregnancy or with perinatal outcomes. Treatment with asthma medications before pregnancy and during gestation also appear to be safe for the mother and for the unborn child, providing support for the current practice of optimal pharmacological management of asthma in women of childbearing age.

This thesis presents an exploratory case study evaluation of a dramatherapy intervention in a key stage three and four pupil referral unit for permanently excluded young people. Dramatherapy is a creative arts therapy concerned with the relationship between the therapist and the client using the medium of drama or theatre to make sense of life experiences (Landy, 2006). Existing literature suggests that this is a relatively under-researched topic, and there is a need for evidence-based practice to support the use of dramatherapy (Dokter, Holloway & Seebohm, 2011). Through continued engagement with the literature and subsequently the participants and dramatherapists, the research began to take more of an exploratory path, investigating whether change had occurred in dramatherapy and if so why this could have happened. This change was reflected in the research questions. The research questions focused on the perceived changes that were observed by the participants themselves, their dramatherapists or a member of school staff during the period of the intervention; if changes were perceived what within the intervention could have helped bring the changes about, and what factors external to dramatherapy could have influenced the process of the intervention. A pragmatic, mixed-methods approach was initially adopted for this study. A pilot phase, evaluating the perceived impact of dramatherapy for five participants who were receiving dramatherapy was used to guide the development of quantitative measures in the evaluation phase. Three young people participated in the evaluation phase of the study. A single case experimental design was used to help evaluate perceived changes during dramatherapy and in order to explore whether is was possible to measure change in a dramatherapy intervention. This aimed to support the over-riding qualitative element of the study, involving post-evaluation phase semistructured interviews with the three participants, their dramatherapists and one or more member of school staff. Visual analysis of the single case experimental design graphs suggested that the measures may not have been valid or reliable indicators of the participants' behaviours. This raised questions of the appropriateness of the use of quantitative measures with vulnerable young people who may have social, emotional and behavioural difficulties. Thematic analysis of the qualitative interviews identified that the participants, their dramatherapists and/or a member of staff had observed that the participants were able to make changes within therapy, and within the pupil referral unit. Thematic analysis identified that factors of the therapeutic space, the relationship, and the use of metaphor and projective techniques were seen to have helped the young people make changes. Thematic analysis identified that the process of the dramatherapy intervention was seen to have been influenced by systemic factors. The findings were examined with reference to the relevant literature. Strengths and limitations of the study were discussed. Potential future research and implications for practice are outlined.

Transcranial direct current stimulation (tDCS) is a popular non-invasive brain stimulation technique, which has the potential to modulate cortical excitability. The effects of tDCS are known to outlast the stimulation period, and in some cases, repeated applications have been found to produce long lasting clinically relevant effects. The primary aim of this thesis was to explore the reliability and therapeutic potential of this technique. In Chapters 3 and 4 transcranial magnetic stimulation (TMS) was used to measure tDCS effects. These experiments revealed substantial variability regarding the way in which healthy adults responded to stimulation. Notably, there were differences between participants regarding the direction and magnitude of change in cortical excitability. Furthermore, even when group level effects were found reliably, there was substantial intra-subject variability across repeated testing sessions. Subsequent experiments in Chapters 5 and 6, explored the biological and behavioural effects of tDCS in individuals with Gille de la Tourette’s syndrome (GTS). GTS is a neurodevelopmental disorder characterised by motor and phonic tics which have been linked to hyper excitability within motor-cortical regions. Therefore, these experiments aimed to reduce cortical excitability of targeted regions in the hope that this would impact on tics. Disappointingly, no such effects were found immediately after a single session of tDCS (Chapter 5). Consequently, it was hypothesised that repeated applications may be necessary for significant reductions in tics to occur. This was investigated in Chapter 6 using an in-depth case study. The results were encouraging, in particular there was a substantial drop in tics following 10 days of tDCS at 1.5mA intensity. The stimulation was well tolerated and the treatment regimens were closely adhered to, despite tDCS being delivered in the participants own home with remote supervision. A weaker stimulation intensity was not as effective. The findings of Chapters 3-6 highlight that the optimal stimulation parameters may vary from person to person, and that exploration of individual data is critical in therapeutic contexts. The results also suggest that tDCS may be helpful as a treatment for GTS and furthermore highlight the feasibility of home use stimulation.

This thesis compared the effect on weight loss of either replacing diet beverages (DBs) with water or continuing to consume DBs (study 1 in healthy overweight and obese, n=89 and study 2 in patients with type 2 diabetes, n=81) adults during a 24-wk weight-loss program (for study1 and 2) and 18 month weight loss and weight maintenance plan (for study3, n=89). In study 1, compared with the DB group, the water group had a greater decrease in weight (1.2kg more weight loss in the water group compared with the DBs Group ,P=0.015), BMI (0.5 kg/m² more BMI reduction in the water compared with the DBs Group ,P=0.002), fasting insulin (1 mU/l more Fasting insulin reduction in the water compared with the DBs Group,P < 0.001), homeostasis model assessment of insulin resistance (HOMA-IR)(0.2 more HOMA-IR reduction in the water compared with the DBs Group, P < 0.001) and 2-h postprandial glucose(0.305 mmol/l more 2hpp reduction in the water compared with the DBs Group,P < 0.001). In study 2, weight (2.5 kg more weight loss in the water compared with the DBs Group, P=0.005) and BMI (0.9 kg/m² more BMI reduction in the water group compared with the DBs Group, P=0.005) decrease after 18 months in the water group compared with the DBs group was significant. There was also a greater reduction in fasting insulin levels (1.8 mU/l more Fasting insulin reduction in the water group compared with the DBs Group,P < 0.001), better improvement in HOMA-IR (0.5 more HOMA-IR reduction in the water group compared with the DBs Group, P < 0.001), a greater decrease in 2-h postprandial plasma glucose (0.5 mmol/l more 2hpp reduction in the water group compared with the DBs Group, P < 0.001) and glycated hemoglobin (0.2 more HbA1c reduction in the water group compared with the DBs Group, P=0.030) in the water group compared with the DBs over 18 months. In study 3, obese participants with Type 2 diabetes in the water group of study 2 had more weight loss (1.16 kg more weight loss in the water group compared with the DBs Group, P=0.006) and BMI (0.5 kg/m² more BMI reduction in the water group compared with the DBs Group, P=0.006). Also reduction of fasting insulin (1.6 mU/l more Fasting insulin reduction in water group compared with DBs Group,P < 0.001), fasting plasma glucose (0.3mmol/l more Fasting plasma glucose reduction in the water group compared with the DBs Group, P=0.003), HOMA-IR (0.7 more HOMA-IR reduction in the water group compared with the DBs Group, P=0.003) and 2 hour postprandial glucose (0.3 mmol/l more 2hpp reduction in the water group compared with the DBs Group, P=0.027) was greater in the water group. By contrast, changes in waist circumference and lipid profiles were not significantly different between the two groups in these three studies. Replacement of DBs with water after the main meal in obese and overweight healthy and type 2 diabetic women who were regular users of DBs may cause greater weight reduction during 24 weeks and also in the longer period of an 18 month weight management program. In addition, replacement of DBs with water offers clinical benefits to improve insulin resistance. Generally, better improvements in energy and carbohydrate metabolism may occur when water rather than DBs is consumed over a weight loss program.

Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) on the brain is a revolutionary method that provides in-vivo access to tissue macrostructure non-invasively (Basser et al., 1994). Recently, DW-MRI has been shown to have great potential in characterising brain microstructure, such as diameter and size distribution of neuronal fibres, features that were available so far only postmortem or through animal studies (Zhang et al., 2011). Using a process known as Tractography the existence of brain connections can be estimated using a set of DW images (Basser et al., 2000). The main aim of this thesis is to develop efficient methods for studying Tractography within a Bayesian framework. In order to characterise the white matter in the brain we focus on the widely used partial volume model (Behrens et al., 2003). We describe methods that are both time and computationally efficient for estimating the parameters of the partial volume model, before reparametrising the model, so that parameter estimation is viable in some special cases. The partial volume model allows for multiple fibre orientations so we develop methodology to choose between the number of white matter fibres in a voxel. We then take into account the uncertainty in the number of fibre orientations and provide a Fully Probabilistic Tractography method as an alternative to existing Tractography algorithms. Finally we look into the Global Tractography model (Jbabdi et al., 2007) and develop efficient methods for inferring connections between brain regions by investigating methods based on Thermodynamic Integration.

The Kingdom of Saudi Arabia (KSA) is dedicated to implementing technology within the country and E-government is one of these technologies. However, although significant investment has been made, there has been little progress in this area. The purpose of this study is to identify the key cultural drivers and barriers that are influencing the progress of e-government, by understanding employees’ perceptions and acceptance of the phenomenon. The aim, therefore, is to identify the major cultural aspects that are currently influencing the adoption and implementation of e-government in the public sector in the KSA, as reflected in the behaviour and attitudes of government employees involved in the e-government service delivery. For the research design framework model I examined and analyzed earlier studies to provide an appropriate framework for e-government adoption in the public sector in the KSA. This framework could be valuable in guiding the policy makers and the government in recognizing the proper requirements on a cultural level for e-government adoption in the public sector. The proposed framework highlights and identifies some of the cultural aspects that could drive and hinder the process of adoption. Furthermore, the research method in this research adopts a qualitative approach by conducting three case studies in three public organizations in the KSA. In-depth interviews were conducted to gather primary data from thirty-two employees. The data collection took around three to four months to complete in the field. The research reveals that culture has a significant influence on employees when dealing with e-government implementation in the public sector. In addition, the research encountered several limitations in that I conducted, a female from Saudi Arabia living and working in a conservative Arab culture, who carried out in-depth interviews with male employees in three public sectors. This resulted in a number of exacting challenges which had to be faced. The value and originality of this research is illustrated in the method I chose to employ. Adopting a qualitative research methodology involved me in conducting in-depth interviews with employees. As a female Arab, it was inevitable that I would have to undergo a difficult and complex journey to gather the required data. The nature of the country’s conservative society played a role in this aspect. However, this is part of the culture and fabric of the country, and culture is the essence of this research. Hence, this research study offers an insight into the experiences I encountered in employing this qualitative research study.

The project presents design of technology production of the hinge made of metal sheet plate 11 321. The variant proposed solutions have been designed manufacturing cutting and bending technology in transfer combined die. These themes were elaborated in literatures studies. As a working machine was selected eccentric press LEN 40 C of Slovak producer TOMA INDUSTRIES s.r.o., Trnava, with a nominal force 400 kN. Functional parts are made of tool steel 19 436. In economic results was defined cost of one piece including manufacturers profit and the break-even point, which is coming after production of 151 966 pieces.

The thesis concerns the layout of manufacture technology of the bracket for TV wall mount. Based on a trade-off study of several technologies, a solution using a compound tool was selected as the most appropriate for given application. Non-alloy quality steel 11 321.1 was selected as a material for the bracket, with a synthetic paint applied as a surface finish. Analysis of manufacturing parameters was conducted, based on which the two-stroke crank press LKDR 200 was selected. Capability of that machine is sufficient in terms of press force and working space. Forming tools are made of high alloy tool steel 19 436.4, heat treated by quenching and annealing. An evaluation of economic aspects is included in the thesis.

This study presents a mixed methods investigation into the efficacy of an indicated CBT-based intervention for addressing anxiety in a sample of secondary school students within the UK. Phase One of the study employs a quasi-experimental evaluation of a CBT-based intervention. 18 participants (7 male, 11 female, mean age: 12 years 6 months) were allocated to intervention (n=8) or wait-list comparison (n=10) conditions using a matched pairs process. The intervention comprised six sessions of a CBT-based programme, delivered by teaching assistants trained in the principles of CBT; wait-list participants attended their usual lessons. Phase One investigated the effects of intervention participation upon students’ self-reported anxiety and parent-reported perceptions of student anxiety, using the respective versions of the Spence Children’s Anxiety Scale (SCAS and SCAS-P). Results demonstrated that there were no statistically significant effects upon student-reported anxiety or parent-reported perceptions of student anxiety. Parents of participants within the wait-list condition reported increased student anxiety during the intervention phase, albeit this trend did not reach statistical significance. Phase Two represents a qualitative exploration of participants’ perceptions of their post-intervention anxiety regulation abilities and their insight into the programme mechanisms. This phase incorporated Focus Group and Nominal Group Technique approaches, with data reviewed through Thematic Analysis. Findings suggested that participants perceived intervention attendance to have developed their knowledge and understanding of strategies which may either a) actively address the causes of their anxiety or b) enable them to manage the physiological, emotional, cognitive and behavioural implications of anxiety. Participants indicated that intervention participation had increased their understanding of the importance of seeking social support for managing anxieties. Key methodological reflections for this two-phase design are discussed. Findings are compared to the wider literature regarding anxiety and CBT approaches in children and young people. The implications of these findings for future research and the practice of Educational Psychologists are considered.

This project aimed to prove the existence of fine subdural veins hypothesised to be the source of intracranial bleeding seen in cases of accidental and non-accidental traumatic head injuries, and consequently illustrate their anatomical structure. This was important in contributing towards establishing the causal mechanism for traumatic intracranial bleeding, and was particularly applicable in unexplained traumatic head injuries in cases of possible child abuse. These issues are on-going, worldwide concerns that have been of public as well as scientific concern for many years. To illustrate the fine cerebral vessels, a unique modelling technique was recently developed involving polyurethane resin casting of the brain vasculature. Rat, marmoset, rhesus macaque and human brain tissue were all used. Tissue surrounding the resin perfused vessels were then either macerated to reveal the whole cast, or dissected to illustrate the cast as it would appear in situ. To allow analysis of these fine subdural vessels, various imaging techniques including fluorescence microscopy, light microscopy, confocal microscopy, scanning electron microscopy, transmission electron microscopy, magnetic resonance imaging, micro-computed tomography and 3D X-ray microscopy were used. The existence of subdural vessels was clearly illustrated via gross dissection of both primate and cadaveric material. Fluorescence imaging of resin-filled rat brain histological sections also showed orientation of fine vessels within the subdural space. Magnetic resonance imaging of the human head in vivo, as well as cadaveric material have shown signs of small calibre vessels that have never been previously documented, that are too fine to be bridging veins, yet seem to drain into the superior sagittal sinus. These results prove the existence of subdural vessels, present in a range of different species. Future work will further illustrate the exact morphological structure of these vessels, and biomechanical modelling will be applied to determine the exact forces required to cause them to rupture.