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.

Challengers to provisional republicanism: the official republican movement, people’s democracy and the Irish republican socialist party, 1968–98

The Provisional IRA and its political wing Sinn Féin have attracted by far the greatest scholarly interest of all the players in the Northern Irish conflict. This emphasis is perfectly legitimate, given the centrality of the Provos to so many turning-points in the conflict, from the collapse of Stormont in the early 1970s to the hunger strikes of the following decade and the ceasefires which were followed by the Belfast Agreement. My project, however, looks at political groups that at one time or another challenged the Provos for leadership of the militant, anti-state constituency in Northern Ireland (chiefly based in the Catholic working class). Although never as large or influential as the Provisional republicans, groups such as the Official IRA and the Irish Republican Socialist Party sometimes had a discernible impact on the course of events which is overlooked by most studies, and often pioneered ideas and tactics that were later adopted by the Provos themselves. The idea that republicans should embrace political action and work in broad campaigning alliances was promoted by the IRSP and socialist groups such as People’s Democracy before it was taken up by Gerry Adams and his allies, while the Official IRA supported the principle of a settlement based on democratization of the Northern Irish state, which was later accepted by Sinn Féin in the form of the Belfast Agreement. The goal of my research is to provide a novel perspective on the conflict in Northern Ireland, while engaging with theoretical debates about its character.

A post-structuralist analysis of Irish youth crime prevention policy with specific emphasis on the Garda youth diversion projects

Garda Youth Diversion Projects (GYDPs) have since their beginnings in the early 1990s gained an increasingly important role and now constitute a central feature of Irish youth justice provision. Managed by the Irish Youth Justice Service and implemented by the Gardai and a variety of youth work organisations as well as independent community organisations, GYDPs are located at the crossroads of welfarist and corporatist approaches to youth justice, combining diversionary and preventative aspects in their work. To date, these projects have been subjected to very little systematic analysis and they have thus largely escaped critical scrutiny. To address this gap, this thesis locates the analysis of GYDP policy and practice within a post-structuralist theoretical framework and deploys discourse analysis primarily based on the work of Michel Foucault. It makes visible the official youth crime prevention and GYDP policy discourses and identifies how official discourses relating to youth crime prevention, young people and their offending behaviour, are drawn upon, negotiated, rejected or re-contextualised by project workers and JLOs. It also lays bare how project workers and JLOs draw upon a variety of other discourses, resulting in multi-layered, complex and sometimes contradictory constructions of young people, their offending behaviour and corresponding interventions. At a time when the projects are undergoing significant changes in terms of their repositioning to operate as the support infrastructure underpinning the statutory Garda Youth Diversion Programme, the thesis traces the discursive shifts and the implications for practice that are occurring as the projects move away from a youth work orientation towards a youth justice orientation. A key contribution of this thesis is the insight it provides into how young people and their families are being constituted in individualising and sometimes pathologising ways in GYDP discourses and practices. It reveals the part played by the GYDP intervention in favouring individual and narrow familial causes of offending behaviour while broader societal contexts are sidelined. By explicating the very assumptions upon which contemporary youth crime prevention policy, as well as GYDP policy and practice are based, this thesis offers a counterpoint to the prevailing evidence-based agenda of much research in the field of Irish youth justice theory and youth studies more generally. Rather, it encourages the reader to take a step back and examine some of the most fundamental and unquestioned assumptions about the construction of young people, their offending behaviour and ways of addressing this, in contemporary Irish youth crime prevention policy and practice.

Health of the older worker in Ireland - occupational physical and psychosocial factors in the autumn of work life

Introduction: Worldwide, governments are striving to keep people in work to an older age. However, little is known about the effects of work on an older workforce. This thesis aims to investigate the importance of job characteristics to the antecedents and evolution of cardiovascular disease and functional limitations for the older worker (50+ years). Methods: Three studies were used in this thesis. The 5C (Cork Coronary Care Case- Control) Study investigated the association between job strain and a coronary event in males (n=208) 35-74 years old. The Mitchelstown Study examined the association between job characteristics and positive lifestyle behaviours and further, job characteristics and blood pressure for males and females 50-69 years (n=2,047). Finally, the Cork & Kerry Study investigated the physical effects of manual work and reported functional limitations/disabilities in a sample of 60-80 year olds (n=362). Results: Results from the 5C Study show a clear difference between younger (<50 years) and older (≥50 years) workers, with older workers who had a coronary event more likely to have high job strain and low job control. Data from the Mitchelstown Study showed workers with intermediate possibility for development or high quantitative demands (versus low) at work significantly more likely to have co-occurrence of positive lifestyle behaviours. Further, those who had high possibility for development were more likely to have high systolic blood pressure with no indication of recovery from this activation at night. Physically demanding work as reported by the participants of the Cork & Kerry Study was associated with functional limitations and activities of daily living disability for both the paid and unpaid worker. Discussion: The findings from this piece of work highlight the necessity to examine job characteristics and health outcomes in isolation for the over fifties. The challenge is to get this information into the workplace.

Interaction of additive and quantization noises in digital PLLs

Phase-locked loops (PLLs) are a crucial component in modern communications systems. Comprising of a phase-detector, linear filter, and controllable oscillator, they are widely used in radio receivers to retrieve the information content from remote signals. As such, they are capable of signal demodulation, phase and carrier recovery, frequency synthesis, and clock synchronization. Continuous-time PLLs are a mature area of study, and have been covered in the literature since the early classical work by Viterbi [1] in the 1950s. With the rise of computing in recent decades, discrete-time digital PLLs (DPLLs) are a more recent discipline; most of the literature published dates from the 1990s onwards. Gardner [2] is a pioneer in this area. It is our aim in this work to address the difficulties encountered by Gardner [3] in his investigation of the DPLL output phase-jitter where additive noise to the input signal is combined with frequency quantization in the local oscillator. The model we use in our novel analysis of the system is also applicable to another of the cases looked at by Gardner, that is the DPLL with a delay element integrated in the loop. This gives us the opportunity to look at this system in more detail, our analysis providing some unique insights into the variance `dip' seen by Gardner in [3]. We initially provide background on the probability theory and stochastic processes. These branches of mathematics are the basis for the study of noisy analogue and digital PLLs. We give an overview of the classical analogue PLL theory as well as the background on both the digital PLL and circle map, referencing the model proposed by Teplinsky et al. [4, 5]. For our novel work, the case of the combined frequency quantization and noisy input from [3] is investigated first numerically, and then analytically as a Markov chain via its Chapman-Kolmogorov equation. The resulting delay equation for the steady-state jitter distribution is treated using two separate asymptotic analyses to obtain approximate solutions. It is shown how the variance obtained in each case matches well to the numerical results. Other properties of the output jitter, such as the mean, are also investigated. In this way, we arrive at a more complete understanding of the interaction between quantization and input noise in the first order DPLL than is possible using simulation alone. We also do an asymptotic analysis of a particular case of the noisy first-order DPLL with delay, previously investigated by Gardner [3]. We show a unique feature of the simulation results, namely the variance `dip' seen for certain levels of input noise, is explained by this analysis. Finally, we look at the second-order DPLL with additive noise, using numerical simulations to see the effects of low levels of noise on the limit cycles. We show how these effects are similar to those seen in the noise-free loop with non-zero initial conditions.

Health in the medieval world: Regionality and the bioarchaeology of Ireland and Britain

This study assesses regional health patterns in early medieval Ireland and Britain by analysing and interpreting palaeopathological indicators of stress. This was achieved by incorporating the results of demographic and palaeopathological study into the specific historical contexts. Although relatively small islands, both are home to unique and diverse cultural, physical, and political landscapes, which could potentially affect the general health of the population in different ways. To accurately answer the research question, a bioarchaeological survey of six regions within both islands was carried out, specifically analysing and comparing the demographic profile and general health trends within each region with one another. Results from the analysis have demonstrated statistically significant differences within and between the islands. Inferring that even the more subtle differences observed within the cultural, physical, and political landscapes, such as in the case of Ireland and Britain, can and do affect general health trends. The health of early medieval Ireland and Britain appears to be significantly affected by the physical landscape, specifically a north/south divide. The most northerly regions, Scotland South and Ireland North, manifested higher levels of stress indicators when compared to the more southerly positioned regions. Although it can only be hypothesised what factors within these regions are causing, enhancing or buffering stress, the study has established the potential and necessity for regional work to be continued when interpreting the historical past of these two islands.