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Gain-of-function mutations in the Ki r6.2 and SUR subunits of the KATP channel are associated with neonatal diabetes (ND). I used a mouse model selectively expressing the Kir6.2-V59M mutation in pancreatic β cells (inducible i β-V59M) to compare the effects of sulphonylurea and insulin therapy on neonatal diabetes. Gene expression was induced in adulthood, which caused severe hyperglycaemia and resulted in a major decrease in insulin content, pancreatic j3-cell area, pancreatic islet number, single islet size and total islet area. Insulin secretion and glucose tolerance were also severely impaired. To determine if the preservation of physiological blood glucose levels (- 4mM) alone is sufficient to prevent these effects, or if the closure of the KATP channel is also required, induced iβ-V59M mice were implanted with insulin pellets or a high-dose glibenclamide pellet. Insulin therapy restored blood glucose levels but failed to fully preserve pancreatic islet and β-cell morphology and function. Conversely glibenclamide therapy reduced elevated blood glucose concentrations down to a physiological range and maintained pancreatic islet and β-cell morphology and function. These findings have implications for treatment of human patients suffering from neonatal diabetes

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This thesis explores decision-making and perceptions of decisional quality in parents whose children have undergone newborn bloodspot screening. Newborn bloodspot screening is the programme through which newborn babies are screened for a variety of conditions shortly after birth. In the UK babies are screened for phenylketonuria (PKU), congenital hypothyroidism (CH), sickle cell diseases (SCD), cystic fibrosis (CF) and medium chain acyl-CoA dehydrogenase deficiency (MCADD), with Duchenne muscular dystrophy (DMD) offered as additional screen in Wales. Much has been written about the applicability of consent to newborn bloodspot screening, yet research has tended to revolve around parental knowledge and information provision. These studies say little in terms of actual or perceived decisional quality or whether parents are making an informed choice. Taking an exploratory sequential mixed methods approach, the present study aims to identify and model factors that in fluence parental perceptions of decisional quality within the context of newborn bloodspot screening. The thesis draws on two studies; an exploratory study of parental experiences of newborn bloodspot screening using semi-structured interviews, and a subsequent quantitative phase which analysed data collected through a postal questionnaire. The results of these studies provide significant insights into parental decision-making. Attitudes toward medicine were shown to have a significant causal infl uence on perceived decisional quality through its indirect effect on parental attitudes towards screening. Through the disaggregation of these general and specific attitudes, the significant role of perceived choice is identified. Perceived choice is demonstrated not only to be a significant contributing factor to the perceived quality of decision made, but is also shown to have a strong infl uence on attitudes towards screening through an indirect and positive relationship with perceived knowledge of screening. Both of these elements suggest that the context of screening and its presentation are key determinants of parental decisional quality.

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