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.

An exploratory study on the impact of an early years' preschool intervention programme in the Republic of Ireland

Early years’ education has increasingly been identified as a mechanism to alleviate educational disadvantage in areas of social exclusion. Early years’ intervention programmes are now a common government social policy for addressing social problems (Reynolds, Mann, Miedel, and Smokowski, 1997). In particular, state provided early years’ programmes such as Head Start in the United States and Early Start in Ireland have been established to combat educational disadvantage for children experiencing poverty and socio-economic inequality. The focus of this research is on the long-term outcomes of an early years’ intervention programme in Ireland. It aims to assess whether participation in the programme enhances the life course of children at-risk of educational disadvantage. It involves an in-depth analysis of one Early Start project which was included in the original eight projects established by the Department of Education and Science in 1994. The study utilises a multi-group design to provide a detailed analysis of both the academic and social progress of programme participants. It examines programme outcomes from a number of perspectives by collecting the views of the three main stakeholders involved in the education process; students who participated in Early Start in 1994/5, their parents and their teachers. To contribute to understanding the impact of the programme from a community perspective interviews were also conducted with local community educators and other local early years’ services. In general, Early Start was perceived by all participants in this study as making a positive contribution to parent involvement in education and to strengthening educational capital in the local area. The study found that parents and primary school teachers identified aspects of school readiness as the main benefit of participation in Early Start and parents and teachers were very positive about the role of Early Start in preparing children for the transition to formal school. In addition to this, participation in Early Start appears to have made a positive contribution to academic attainment in Maths and Science at Junior Certificate level. Students who had participated in Early Start were also rated more highly by their second level teachers in terms of goal-setting and future orientation which are important factors in educational attainment. Early Start then can be viewed as providing a positive contribution to the long-term social and academic outcomes for its participants.

Leader's reflections on knowledge, knowing and not knowing: an analysis of change over time

One commonality across the leadership and knowledge related literature is the apparent neglect of the leaders own knowledge. This thesis sought to address this issue through conducting exploratory research into the content of leader’s personal knowledge and the process of knowing it. The empirical inquiry adopted a longitudinal approach, with interviews conducted at two separate time periods with an extended time-interval between each. The findings from this research contrast with images of leadership which suggest leaders are in control of what they know, that they own their own knowledge. The picture that emerges is one of individuals struggling to keep abreast of the knowledge required to deal with the dynamics and uncertainties of organisational life. Much knowledge is tacit, provisional and perishable and the related process of knowing more organic, evolutionary and informal than any structured or orchestrated approach. The collective nature of knowing is a central feature, with these leaders embedded in networks of uncontrollable relationships. In view of the indeterminate nature of knowing, the boundary between what is known and what one needs to know is both amorphous and ephemeral, and the likelihood of knowledge-absences is escalated. A significant finding in this regard is the identification of two critical points where not-knowing is most likely (entry and exit from role) and the differing implications of each. Overtime the knowledge that is legitimised or prioritised is significantly altered as these leaders replace the dogmas that were previously held in high esteem with the lessons from their own experience. This experience brings increased self-knowledge and a deeper appreciation of the values and morals instilled in their early lives. In view of the above findings, this study makes theoretical contribution to a number of core literatures: authentic leadership, role transition and knowledge-absences. In terms of leadership development, the findings point to the necessity to prepare leaders for the challenges they will encounter at the pivotal stages of the leadership role.