Longitudinal study of changes in body mass index, anthropometric measures, dietary intake and physical activity in cohorts of school-going Irish adolescents

The prevalence of obesity worldwide has increased dramatically over the last few decades. Poor dietary habits and low levels of exercise in adolescence are often maintained into adulthood where they can impact on the incidence of obesity and chronic diseases. A 3-year longitudinal study of anthropometric, dietary and exercise parameters was carried out annually (2005 - 2007) in 3 Irish secondary schools. Anthropometric measurements were taken in each year and analysed longitudinally. Overweight and obesity were at relatively low levels in these adolescents. Height, weight, BMI, waist and hip circumferences and TST increased significantly over the 3 years. Waist-to-hip ratio (WHR) decreased significantly over time. Boys were significantly taller than girls across the 3 years. A 3-day weighed food diary was used to assess food intake by the adolescents. Analysis of dietary intake data was determined using WISP©. Mean daily energy and nutrient intakes were reported. Mean daily energy and macronutrient intakes were analysed longitudinally. The adolescents’ diet was characterised by relatively high saturated fat intakes and insufficient fruit and vegetable consumption. The dietary pattern did not change significantly over the 3 years. Boys consumed more energy than girls over the study period. A validated questionnaire was used to assess physical activity and sedentary activity levels. Boys were substantially more active and had higher energy expenditure estimates than girls throughout the study. A significant longitudinal decrease in physical activity levels among the adolescents was observed. Both genders spent more than the recommended amount of time (hrs/day) pursing sedentary activities. The dietary pattern in these Irish adolescents is relatively poor. Of additional concern is the overall longitudinal decrease in physical activity levels. Promoting consumption of a balanced diet and increased exercise levels among adolescents will help to reduce future public health care costs due to weight-related diseases.

An analysis of political efficacy socialisation among threshold voters in the Republic of Ireland

The spread of democracy in the latter part of the twenty first century has been accompanied by an increasing focus on its perceived performance in established western democracies. Recent literature has expressed concern about a critical outlook among younger cohorts which threatens their political support and engagement. Political efficacy, referring to the feeling of political effectiveness, is considered to be a key indicator of the performance of democratic politics; as it refers to the empowerment of citizens, and relates to their willingness to engage in political matters. The aim of this thesis is to analyse the socialisation of political efficacy among those on the threshold of political adulthood; i.e., 'threshold voters'. The long-term significance of attitudes developed by time of entry to adulthood for political engagement during adulthood has been emphasised in recent literature. By capturing the effect of non-political and political learning among threshold voters, the study advances existing research frames which focus on childhood and early adolescent socialisation. The theoretical and methodological framework applied herein recognises the distinction between internal and external political efficacy, which has not been consistently operationalized in existing research on efficacy socialisation. This research involves a case study of 'threshold voters' in the Republic of Ireland, and employs a quantitative methodology. A study on Irish threshold voters is timely as the parliament and government have recently proposed a lowering of the voting age and an expansion of formal political education to this age group. A project-specific survey instrument was developed and administered to a systematic stratified sample of 1,042 post-primary students in the Cork area. Interpretation of the results of statistical analysis leads to findings on the divergent influence of family, school, associational, and political agents/environments on threshold voter internal and external political efficacy.

Early biomarkers to predict grade of encephalopathy following hypoxic ischaemic injury

The standard early markers for identifying and grading HIE severity, are not sufficient to ensure all children who would benefit from treatment are identified in a timely fashion. The aim of this thesis was to explore potential early biomarkers of HIE. Methods: To achieve this a cohort of infants with perinatal depression was prospectively recruited. All infants had cord blood samples drawn and biobanked, and were assessed with standardised neurological examination, and early continuous multi-channel EEG. Cord samples from a control cohort of healthy infants were used for comparison. Biomarkers studied included; multiple inflammatory proteins using multiplex assay; the metabolomics profile using LC/MS; and the miRNA profile using microarray. Results: Eighty five infants with perinatal depression were recruited. Analysis of inflammatory proteins consisted of exploratory analysis of 37 analytes conducted in a sub-population, followed by validation of all significantly altered analytes in the remaining population. IL-6 and IL-6 differed significantly in infants with a moderate/severely abnormal vs. a normal-mildly abnormal EEG in both cohorts (Exploratory: p=0.016, p=0.005: Validation: p=0.024, p=0.039; respectively). Metabolomic analysis demonstrated a perturbation in 29 metabolites. A Cross- validated Partial Least Square Discriminant Analysis model was developed, which accurately predicted HIE with an AUC of 0.92 (95% CI: 0.84-0.97). Analysis of the miRNA profile found 70 miRNA significantly altered between moderate/severely encephalopathic infants and controls. miRNA target prediction databases identified potential targets for the altered miRNA in pathways involved in cellular metabolism, cell cycle and apoptosis, cell signaling, and the inflammatory cascade. Conclusion: This thesis has demonstrated that the recruitment of a large cohortof asphyxiated infants, with cord blood carefully biobanked, and detailed early neurophysiological and clinical assessment recorded, is feasible. Additionally the results described, provide potential alternate and novel blood based biomarkers for the identification and assessment of HIE.

The role of bacterial interspecies communication in polymicrobial infection of the cystic fibrosis lung

There is an increasing appreciation of the polymicrobial nature of bacterial infections associated with Cystic Fibrosis (CF) and of the important role for interactions in influencing bacterial virulence and response to therapy. Patients with CF are co-infected with Pseudomonas aeruginosa, Burkholderia cenocepacia and Stenotrophomonas maltophilia. These latter bacteria produce signal molecules of the diffusible signal factor (DSF) family, which are cis-2-unsaturated fatty acids. Previous studies showed that DSF from S. maltophilia leads to altered biofilm formation and increased tolerance to antibiotics in P. aeruginosa and that these responses require the P. aeruginosa sensor kinase PA1396. The work in this thesis aims of further elucidate the influence and mechanism of DSF signalling on P. aeruginosa and examine the role that such interspecies signalling play in infection of the CF airway. Next generation sequencing technologies targeting the 16S ribosomal RNA gene were applied to DNA and RNA isolated from sputum taken from cohorts of CF and non-CF subjects to characterise the bacterial community. In parallel, metabolomics analysis of sputum provided insight into the environment of the CF airway. This analysis revealed a number of observations including; that differences in metabolites occur in sputum taken from clinically stable CF patients and those with exacerbation and DNA- and RNA-based methods suggested that a strong relationship existed between the abundance of specific strict anaerobes and fluctuations in the level of metabolites during exacerbation. DSF family signals were also detected in the sputum and a correlation with the presence of DSFproducing organisms was observed. To examine the signal transduction mechanisms used by P. aeruginosa, bioinformatics with site directed mutagenesis were employed to identify signalling partners for PA1396. A pathway suggesting a role for a number of proteins in the regulation of several factors following DSF recognition by PA1396 were observed.

Caesarean section and subsequent pregnancy outcome: a Danish register-based cohort study

Background and Aims: Caesarean section rates have increased in recent decades and the effects on subsequent pregnancy outcome are largely unknown. Prior research has hypothesised that Caesarean section delivery may lead to an increased risk of subsequent stillbirth, miscarriage, ectopic pregnancy and sub-fertility. Structure and Methods: Papers 1-3 are systematic reviews with meta-analyses. Papers 4-6 are findings from this thesis on the rate of subsequent stillbirth, miscarriage, ectopic pregnancy and live birth by mode of delivery. Results Systematic reviews and meta-analyses: A 23% increased odds of subsequent stillbirth; no increase in odds of subsequent ectopic pregnancy and a 10% reduction in the odds of subsequent live birth among women with a previous Caesarean section were found in the various meta-analyses. Danish cohorts: Results from the Danish Civil Registration System (CRS) cohort revealed a small increased rate of subsequent stillbirth and ectopic pregnancy among women with a primary Caesarean section, which remained in the analyses by type of Caesarean. No increased rate of miscarriage was found among women with a primary Caesarean section. In the CRS data, women with a primary Caesarean section had a significantly reduced rate of subsequent live birth particularly among women with primary elective and maternal-requested Caesarean sections. In the Aarhus Birth Cohort, overall the effect of mode of delivery on the rate and time to next live birth was minimal. Conclusions: Primary Caesarean section was associated with a small increased rate of stillbirth and ectopic pregnancy, which may be in part due to underlying medical conditions. No increased rate of miscarriage was found. A reduced rate of subsequent live birth was found among Caesarean section in the CRS data. In the smaller ABC cohort, a small reduction in rate of subsequent live birth was found among women with a primary Caesarean section and is most likely due to maternal choice rather than any ill effects of the Caesarean. The findings of this study, the largest and most comprehensive to date will be of significant interest to health care providers and women globally.