Background and aim of research: It has been suggested that expectant and new fatherhood can be a time of confusion and stress and there is an increasing awareness of the importance of supporting men through this complex transition. The aim of this research was to create a depth of understanding regarding how men experience becoming a father for the first time, and to examine the breadth of the entire experience from the antenatal period through the first few weeks of life as 'father'. Method :A descriptive phenomenological approach was chosen for this research, due to its emphasis placed on examining phenomena as they are experienced by the individual in everyday life. Phenomenology allowed for the fathers' individual accounts of their transition and enabled them to discuss the aspects of their experience that they felt to be significant. Results: Eight first time fathers were interviewed, between ten and twelve weeks after the birth of their child. Analysis led to the development of a general structure of early fatherhood, detailing the essential aspects of the experience of becoming a father for the first time that were present for all fathers interviewed. Five constituents of the experience were identified, these were; 'travelling into the great unknown', 'tower of strength', 'oscillating reality', 'the intimate relationship with the baby', 'the new me'. Conclusions: The early experience of becoming a father for the first time is similar to undertaking a complex journey, involving preparation and attempts to create an understanding of the route they will take. A sense of newness exists within every aspect of the experience. Throughout the experience there are moments when the father has difficulty engaging with the reality of his impending or new fatherhood, yet he maintains a need to provide support for his partner. The birth brings with it the creation of the relationship between father and child, a relationship which affirms his new role. The findings of this research highlight the importance of assisting fathers with this journey, offering them the help and support they need to be able to feel prepared and to have a clearer understanding of how to negotiate the various paths their new role may take them down.

It has recently been recognised that concepts of health contain multiple dimensions. One area that has received little attention in archaeology is that of health and well-being, so this research seeks to contribute to this area of study. It does so by investigating healthiness in the late Iron Age and Romano-British periods. The literature review explores current thinking around this topic, and confirms that aspects of good health mattered to people in the past. The research explores small finds that are traditionally associated with personal use (mirrors, combs, glass unguent containers, bronze cosmetic grinders and other additional toilet items) from the main urban-type settlements of south-east Britain. The investigation included collecting data concerning the sites, contexts, dates, materials, types, forms, colours and decoration ofthese objects, and any associated archaeological remains found with these items. Given the social nature ofthis work, a contextual approach was central to the design. The research takes an interpretive interdisciplinary position that draws on theoretical models based on the self and other, the body and face, the senses and perception, as well as concepts from material cultural studies, such as agency. Patterns seen in the data-set coupled with theoretical frameworks, and understandings of late Iron Age and Roman life, are brought together, and offer a means of interpreting how and why some of these small finds contributed to practices ofmaintaining good health. These proposals include healthiness in personhood and domestic and public life, in religion and the control of healthiness.

Collectively, these writings significantly contribute to our academic and clinical knowledge of assessing dementia. We have learned a great deal from studying and helping people with Down's syndrome; however, perhaps more importantly, this work should contribute significantly to our rather limited knowledge of assessing dementia in people with Down's syndrome and thus may step towards improving and widening access to service provision for these valued people.

Background: There is increasing evidence that psychological factors such as stress and depression might have an influence in the onset of many physical illnesses, but less is known about their effect from early life. This study is an epidemiological life-course analysis to test: (1) the hypotheses that early-life psychological factors are linked to later development of chronic disease (cancer, diabetes, and asthma) in mid-life, (2) whether such associations can be explained by pre-existing confounding factors, and (3) whether such links are mediated by other biological, behavioural, social, and cognitive factors. Methods: The data were from two ongoing prospective longitudinal studies following the lives of about 17,000 people born in Great Britain in one particular week in 1958 and 1970. Outcomes included diagnosis of cancer, asthma, and diabetes up to the year 2000. Psychological measures taken from ages 5 to 16 years were the main predictors. Associations were examined using discrete-time survival analysis and structural equation models, adjusting for potential confounders and mediators. Results: In the 1958 cohort, a standard deviation increase in the scores of conduct problems at ages 11 and 16 years, indicating severe behavioural problems, was associated with 2 to 34% increase in the odds of being diagnosed with cervical or all cancers after adjusting for childhood confounders. These effects were completely mediated by adulthood psychological distress and health behaviours. Only the teacher-reported behavioural problems significantly predicted the risk of diabetes after adjusting for family history of diabetes and sex (odds ratios of 1.05 to 1.08, p<O.Ol). These associations were partly mediated by mid-life psychological distress and adiposity. Significant associations were observed between most of the childhood psychological factors and adult-onset asthma even after adjusting for possible confounders and mediators. Conclusions: Childhood problem behaviours may predict chronic disease risk over the life-course either directly or mediated through adulthood factors. A consistent pathway among the disease groups was through adulthood psychological distress. Such continuities from childhood to adulthood psychological distress to the disease may be explained by the substantial biological plausibility of the association between psychological factors and physical health, primarily via alteration of the endocrine and the immune systems. The importance of promoting positive emotional and behavioural development in early life is stressed.

Post-mortem blood drug concentrations vary greatly and as a consequence of post-mortem change and redistribution may not reflect the concentration at the time of death. Tissues that are located away from central drug reservoirs and that lack esterase activity, e.g. muscle and vitreous humour (VH), have the potential to provide more reliable post-mortem toxicological specimens. In the absence of a blood sample the toxicologist may have to rely on such tissues yet few studies have been undertaken to examine the relationship between drugs in blood and less conventional tissues at the time of death. The purpose of this study was to investigate the distribution of opiates (heroin specific compounds) and cocaine and their respective metabolites in VH and muscle with a view to elucidating the interpretive value of these tissues. Analytical methods were developed and validated to measure drug concentrations in blood, VH and muscle, including throughout the rectus femoris thigh muscle, in cases of drug related death. To assist with interpretation of drug concentrations measured in post-mortem tissues the in vitro stability of cocaine and 6-acetylmorphine (6AM) was examined during the putrefactive process and under different storage conditions. Relationships between blood and tissue drug concentrations were assessed in relation to case circumstances with particular focus on the approximation of survival time. In contrast to a report previously published in the literature, this study found the concentration of cocaine, and its metabolites, benzoylecgonine (BZE) and cocaethylene (COET), to be uniformly distributed throughout the thigh muscle (n = 7). Concentrations of cocaine in muscle were markedly higher than in blood and correlated well with the blood. The stability of cocaine in muscle tissue was found to greatly exceed that in blood and VH. These preliminary results also indicated that the cocaine to BZE ratio measured in both muscle and VH may be of value in the assessment of survival time. These findings promote the use of muscle as a toxicological specimen for cocaine determinations. Further work is required to validate these findings and to examine the distribution of opiates in muscle, which could not be assessed in this study. The relationship between femoral blood and vitreous humour morphine concentration (n = 70) was found to be dependent on survival time and possibly influenced by accumulation of morphine in the VH. These findings demonstrate that the concentration of morphine in blood cannot be inferred from that measured in the VH. The VH provided a useful adjunct to interpretation owing to the prolonged detection of 6AM in this matrix. The addition of 1.5% sodium fluoride to VH was found to be essential for 6AM stability during storage. The utility of rapidly metabolised heroin specific compounds in blood as indicators of survival period following heroin intake and the role of concomitant drug consumption in heroin fatalities was also discussed in this thesis.

Research Aims Practice development accreditation is growing rapidly as it is praised for transforming cultures of health care, inciting empowerment, instigating multidisciplinary teamwork and creating more effective services. However, literature is vague on what occurs during accreditation, the role of culture within this process and the experiences of different professional groups in practice development. This research therefore sought to address the following research aims: To investigate practice development accreditation by studying a unit undertaking this process To examine the culture of a unit during accreditation To portray a multidisciplinary account of practice development Method These aims were investigated by conducting a twelve month observational study of a group undertaking the accreditation process. Despite the accreditation attempt being unsuccessful, important concepts around leadership and culture emerged. Findings This study found that the core group of practitioners instigating practice development lacked shared beliefs, aims or commitment which caused disputes (particularly over the distribution of work) and that a lack of management support dampened morale and made progression difficult. The core group's leadership style also hindered the accreditation attempt as they both restricted and forced involvement from the staff, leaving them feeling unempowered and reluctant to participate. Finally, the participants were unable to overcome divides based on hierarchical and professional identity to work as part of a multidisciplinary team in order to implement practice development. Recommendations Four recommendations for the instigators of any empowering change initiative emerged. These are: i) to create a 'vision' in order to ensure the entire organisation understands the purpose and goal of implementing changes; ii) to erode divides between employees that are based on professional and hierarchical identities; iii) to create succession plans in order to maintain effective leadership; iv) those initiating change should understand the notion of functional conflict. Further Research This study suggests further research is needed into the roles of excluded professionals in practice development, to explore the relationship between accredited and non-accredited units within organisations, to assessthe impact of gender within practice development units, to discover how units successfully achieve accreditation and the strategies utilised by ethnographers to disengage from the field.

Disorders of male reproductive health which manifest at birth (cryptorchidism, hypospadias) or in young adulthood (testicular germ cell cancer and low sperm counts), are common and may be increasing in incidence. These disorders have a common fetal origin and share risk factors; consequently they are hypothesized to comprise a testicular dysgenesis syndrome (TDS). TDS arises when maldevelopment (dysgenesis) of the fetal testis results in hormonal malfunctions and abnormal development and function of the somatic cells. It is thought that the suppressed intratesticular testosterone levels associated with TDS may account for subsequent low sperm counts, via a reduction in perinatal Sertoli cell proliferation/number. Sertoli cells do not express androgen receptors (AR) in fetal life in the human or rat, so it is hypothesised that any androgen effects on Sertoli cell number occur indirectly, via the AR positive peritubular myoid cells. Evidence from the di (n‐butyl) phthalate (DBP)‐treated rat model for TDS suggests that reduced androgen action may play a role in testicular dysgenesis as in patients with complete androgen insensitivity syndrome (CAIS; ‘testicular feminization’), in whom focal areas of testicular dysgenesis have been reported. The studies in this thesis sought to establish if reduced androgen levels/action in the fetal rat testis contribute to putative testicular dysgenetic features, namely reduced Sertoli cell number, occurrence of multinucleated gonocytes or abnormal aggregation of fetal Leydig cells, the precursor of focal dysgenesis. Pregnant rats were exposed to treatments or co‐treatments expected to manipulate testicular testosterone levels (DBP, testosterone propionate; TP) or action (flutamide, DMBA) or to induce intrauterine growth restriction (dexamethasone), another risk factor for TDS. The aforementioned endpoints were analysed in fetal testes and related to testicular testosterone levels and peripheral androgen action (anogenital distance). The same endpoints were evaluated in mice with inactivation of the androgen receptor (tfm or ARKO mice). As androgen action is assumed to be mediated indirectly, via the peritubular myoid cells, changes in peritubular myoid cell number and function were investigated in testes with suppressed androgens. In vitro studies were also used to investigate the role of androgens in Sertoli cell proliferation. Fetal rat testis explants were cultured with various chemicals designed to manipulate androgen action and Sertoli cell proliferation. Potential non‐androgen related mechanisms of DBP action were investigated using Taqman RT‐PCR to determine the mRNA expression of key developmental genes after exposure to DBP. Sertoli cell number was reduced after exposure to treatments that reduced testicular testosterone levels, i.e. DBP alone or as a co‐treatment, TP and dexamethasone. Sertoli cell numbers in ARKO mice were also significantly reduced. The occurrence of multinucleated gonocytes and large Leydig cell clusters were induced after exposure to DBP, alone or as a co‐treatment, but not after exposure to TP or dexamethasone, and these dysgenetic endpoints did not occur either in tfm or ARKO mice. Rats exposed in utero to DBP have reduced testicular testosterone levels, however peritubular myoid cell number was unaffected by DBP, though AR expression in the peritubular myoid cells was delayed, and laminin and vimentin expression in Sertoli cells was altered after DBP exposure. DMRT‐1 and DAX‐1 mRNA expression levels were significantly reduced after DBP exposure, but this reduction was no longer evident once mRNA expression was corrected for Sertoli cell number. In conclusion, these studies provide strong evidence that androgens play a role in regulation of Sertoli cell number/proliferation, and this is supported by a comparable reduction in Sertoli cell number in ARKO and tfm mice. However, since the treatments that reduce testicular testosterone in the rat, may also have a direct affect on the Sertoli cells, this alternate mechanism of action cannot be ruled out, and the administration of a treatment that reduces testicular testosterone without directly affecting Sertoli cells is required. These studies also show that reduced testicular testosterone levels are associated with multinucleated gonocyte formation and fetal Leydig cell aggregation, although this evidence it is not supported by parallel findings from the TP and dexamethasone exposed rats or the ARKO and tfm mice, as neither of these endpoints were identified as being affected in these animals. Aside from the delay in AR expression, there were no obvious changes in peritubular myoid cell number or the peritubular myoid cell markers examined in testes deprived of androgens, although there are other markers that could be investigated. mRNA analysis of the developmental genes investigated after DBP exposure, demonstrated no change in expression after correction for Sertoli cell number, suggesting that they do not play a role in the dysgenetic features observed in DBP exposed testes.

This thesis is my autoethnographic account as I pursue a career as a Service User Representative with the Dorset Mental Health Forum over several years leading up to 2010. This is a period of change in both the social care and health worlds as they impact on to people suffering from mental distress. In this period are introduced Personal Budgets and a three-year pilot scheme to look at the viability of rolling out Personal Health Budgets, in which Dorset is selected as one of 20 sites nationally. There is also a change of government from a Labour administration to a coalition of the Conservative and Liberal Democrat parties, but this does not seem to have changed the planned modernisation of both social care provision and healthcare provision started by the outgoing Labour government. Also in this period we see the wide-ranging revision of the Mental Health Act 1983. My original contribution to knowledge is in describing the development of a service user representative model that works well in Dorset, UK. This thesis is not about the history and development of the mental health service user involvement but I do offer a précis of the history of service user representation for those unfamiliar with it. This thesis is laid out in roughly chronological order. I try to show how I changed my views with the help of other people over the period. I also try to explain what it is that ails me. The reason I do this is to paint a picture of a person who is in general "normal" but suffers from mental disorders that sometimes alter the way he sees the world. It is with this backdrop that I ply my trade of being representative of and to other mental health service users. I lead the reader from a consideration of method and methodology and ethics, through the precursors of my mental illness, to how that illness has been treated by the National Health Service, and how it impacts on my role. The main way that I do this is by offering a vignette of my life and then immediately afterwards analysing that vignette in the light of emergent themes. In this way, I ensure that the emergent themes are themselves based in a reality that can be accessed to some degree by the reader. There were challenges along the way including personal ones, such as having to take time out from my studies to attend courses of psychological treatment and having several heart attacks leading to hospitalisation, as well as the usual ones of finding people to contribute to my research. I end this thesis by offering a model that service users may find illuminating when setting up their own service user representation services.

Previous studies suggested that teniposide is a strong clastogen, and that the DNA breakage effect of this drug is mediated by the nuclear enzyme topoisomerase II. Ripley et al found evidence for a correspondence between sites of acridine-induced frameshift mutations in bacteriophage T4 and sites of in Vitro DNA cleavage by T4 topoisomerase II. To identify the sequence specificity of teniposide-induced deletion and insertion mutations in mammalian cells, the CHO-D422 cell line, which is hemizygous at the aprt locus, was employed in this study. Sixty-eight teniposide-induced and 42 spontaneous aprt mutants were analyzed at the DNA sequence level. Compared with the spectrum of spontaneous mutations in which two thirds of the mutations are base substitutions, two thirds of teniposide-induced mutations are deletions and insertions of different sizes. Significant site correspondence between teniposide-induced deletion/insertion mutations and in vitro DNA double strand cleavages by purified mammalian topoisomerase II was also found in this study, which suggests that the majority of teniposide-induced deletions and insertions observed in this study were generated at the sites of topoisomerase II mediated DNA double strand breaks in the cells. However, considering the positions of the double cleavage sites in the mutation sequences, no consistent pattern was found which could suggest a unified mechanism of DNA double strand break repair. Three models are proposed to try to explain the possible events occurring in the cells following teniposide exposure which resulted in observed deletion and insertion mutations.

Summary: 1. The type of animal blood used in preparing blood agar plates did not significantly affect the demonstration of hemolysis by any streptococcal species except for S.faecalis. S.faecalis more consistently displayed an alpha reaction on sheep blood agar while expressing a beta reaction on horse and rabbit blood agars. 2. A recommended scheme for identifying streptococci, adaptable to most any clinical laboratory, was developed and is outlined in Table 13. 3. S.agalactiae (group B) was the most frequent beta hemolytic streptococcal isolant. Significantly, it was the only species over-all to be recovered from every clinical source. The CAMP test proved to be the best method for the presumptive identification of the group B streptococci. 4. The alpha streptococci were isolated in substantial numbers from a variety of infectious situations suggesting that their role in infection may be greater than previously believed. 5. S.avium accounted for a greater percentage of group D isolations than previously reported in other studies of a similar nature. 6. The bile-esculin test was supported as the best nonserological method for distinguishing the group D streptococci. Arginine hydrolysis was shown to be the best method for distinguishing between the enterococci and the nonenterococci. The test commonly used for this purpose, growth in 6.5% NaCl, resulted in the misidentification of S.avium as an enterococcal species. 7. Urinary tract isolants from every division (notably S.agalactiae, S.mutans. and S.faecalis) exhibited patterns of overall greater antibiotic resistance than those strains isolated from other sources. 8. Among the group D species, S.faecalis displayed the greatest antibiotic resistance followed by S.avium, S.faecium, and S.bovis. S.avium, a nonenterococcus. showed greater drug resistance than S.faecium, an enterococcus. S.bovis was the least resistant with susceptibility patterns more closely related to the alpha streptococci.