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.

Between the worlds: otherworld women as intermediaries in early Irish literature

This thesis examines the ways in which Otherworldly women acted as intermediaries between the Otherworld and mortal world in early Irish literature. First it establishes the position of women in early Ireland so that appropriate comparisons can be made between mortal and Otherworld women throughout the thesis. Also, it defines what is meant by the ‘Otherworld’ and its relevence to the early Irish. It then goes on to discuss the differing goals of various intermediaries in early Irish texts, and in what manner they interact with mortals. It briefly looks at how Otherworld male intermediaries are treated differently in the literature, and why early authors might have used women in these roles as often as they did.

A knowledge management system to optimise comfort throughout the building life-cycle

Comfort is, in essence, satisfaction with the environment, and with respect to the indoor environment it is primarily satisfaction with the thermal conditions and air quality. Improving comfort has social, health and economic benefits, and is more financially significant than any other building cost. Despite this, comfort is not strictly managed throughout the building lifecycle. This is mainly due to the lack of an appropriate system to adequately manage comfort knowledge through the construction process into operation. Previous proposals to improve knowledge management have not been successfully adopted by the construction industry. To address this, the BabySteps approach was devised. BabySteps is an approach, proposed by this research, which states that for an innovation to be adopted into the industry it must be implementable through a number of small changes. This research proposes that improving the management of comfort knowledge will improve comfort. ComMet is a new methodology proposed by this research that manages comfort knowledge. It enables comfort knowledge to be captured, stored and accessed throughout the building life-cycle and so allowing it to be re-used in future stages of the building project and in future projects. It does this using the following: Comfort Performances – These are simplified numerical representations of the comfort of the indoor environment. Comfort Performances quantify the comfort at each stage of the building life-cycle using standard comfort metrics. Comfort Ratings - These are a means of classifying the comfort conditions of the indoor environment according to an appropriate standard. Comfort Ratings are generated by comparing different Comfort Performances. Comfort Ratings provide additional information relating to the comfort conditions of the indoor environment, which is not readily determined from the individual Comfort Performances. Comfort History – This is a continuous descriptive record of the comfort throughout the project, with a focus on documenting the items and activities, proposed and implemented, which could potentially affect comfort. Each aspect of the Comfort History is linked to the relevant comfort entity it references. These three components create a comprehensive record of the comfort throughout the building lifecycle. They are then stored and made available in a common format in a central location which allows them to be re-used ad infinitum. The LCMS System was developed to implement the ComMet methodology. It uses current and emerging technologies to capture, store and allow easy access to comfort knowledge as specified by ComMet. LCMS is an IT system that is a combination of the following six components: Building Standards; Modelling & Simulation; Physical Measurement through the specially developed Egg-Whisk (Wireless Sensor) Network; Data Manipulation; Information Recording; Knowledge Storage and Access.Results from a test case application of the LCMS system - an existing office room at a research facility - highlighted that while some aspects of comfort were being maintained, the building’s environment was not in compliance with the acceptable levels as stipulated by the relevant building standards. The implementation of ComMet, through LCMS, demonstrates how comfort, typically only considered during early design, can be measured and managed appropriately through systematic application of the methodology as means of ensuring a healthy internal environment in the building.

Landscapes of kingship in early medieval Ireland, AD 400–1150

This thesis explores the evolution of kingship in early medieval Ireland (AD 400–1150) through a kingdom based and multi-scalar approach to royal landscapes. Through exploring the role of place and landscape in the construction of early medieval Irish kingship, this study will assess the relationship between the social, economic and ideological roles of the king in Irish society. Kingship in Ireland was vested in places, such that royal landscapes were the pre-eminent symbol of regality and authority. As such, an interdisciplinary study of kingship grounded in archaeological methodologies has a unique potential to contribute to our knowledge of the practice of kingship. Consequently, this research considers the material apparatus of different scales of kingships and explores the role of landscape in the construction of kingship and the evolution of kingdoms. It takes two major case studies; (i) Cashel, Munster and the Éoganachta federation; and (ii) the Uí Néill, Tara and the Síl nÁedo Sláine kingdom of Brega. Through interdisciplinary methodologies it charts the genesis and development of political federations, focusing specifically on the role that royal landscapes’ played in their evolution. Similarly, this thesis engages critically with the nature of assembly places and practices in Ireland, and focuses specifically on issues pertaining to the nature of assembly and the archaeological manifestation of such practices. It includes a list of 115 landscapes identified as assembly places, and through the analysis of this material, this thesis examines the ways in which different types of royal sites articulated together to create royal landscapes implicated in the exercise of kingship, and the construction and maintenance of authority. Moreover, through the analysis of assembly places within the context of the development of kingdoms, and structures of jurisdiction and administration, it also investigates the evolution of supra-regional scales of identity and community associated with the emergence of major political federations in early medieval Ireland.

Aesthetic campaigns and counter-campaigns. Jorge Luis Borges and a century of the Argentine detective story (1877-1977)

This cultural history of Argentine crime fiction involves a comprehensive analysis of the literary and critical traditions within the genre, paying particular attention to the series of ‘aesthetic campaigns’ waged by Jorge Luis Borges and others during the period between 1933 and 1977. The methodological approach described in the introductory chapter builds upon the critical insight that in Argentina, generic discourse has consistently been the domain, not only of literary critics in the traditional mould, but also of prominent writers of fiction and specialists from other disciplines, effectively transcending the traditional tripartite ‘division of labour’ between writers, critics and readers. Chapter One charts the early development of crime fiction, and contextualises the evolution of the classical and hardboiled variants that were to provide a durable conceptual framework for discourse in the Argentine context. Chapter Two examines a number of pioneering early works by Argentine authors, before analysing Borges’ multi-faceted aesthetic campaign on behalf of the ‘classical’ detective story. Chapter Three examines a transitional period for the Argentine crime genre, book-ended by the three Vea y Lea magazine-sponsored detective story competitions that acted as a vital stimulus to innovation among Argentine writers. It includes a substantial treatment of the work of Rodolfo Walsh, documenting his transition from crime writer and anthologist to pioneer of the non-fiction novel and investigative journalism traditions. Chapter Four examines the period in which the novela negra came to achieve dominance in Argentina, in particular the aesthetic counter-campaigns conducted by Ricardo Piglia and others on behalf of the hard-boiled variant. The study concludes with a detailed analysis of Pablo Leonardo’s La mala guita (1976), which is considered as a paradigmatic example of crime fiction in Argentina in this period. The final chapter presents conclusions and a summary of the dissertation, and recommendations for further research.

Reading Lydgate's Troy Book: patronage, politics, and history in Lancastrian England

This thesis, Reading Lydgate's Troy Book: Patronage, Politics and History in Lancastrian England, discusses the relationship between John Lydgate as a court poet to his patron Henry V. I contend that the Troy Book is explored as a vehicle to propagate the idea that the House of Lancaster is the legitimate successor to King Richard II in order to smooth over the usurpation of 1399. Paul Strohm's England's Empty Throne was a key influence to the approach of this thesis' topic. I examine that although Chaucer had a definitive impact on Lydgate's writing, Lydgate is able to manipulate this influence for his own ambitions. In order to enhance his own fame, Lydgate works to promote Chaucer's canon so that as Chaucer's successor, he will inherit more prestige. The Trojan war is seen in context with the Hundred Years War, and can be applied contextually to political events. Lydgate presents characters that are vulnerable to human failings, and their assorted, complicated relationships. Lydgate modernises the Troy Book to reflect and enhance his Lancastrian society, and the thesis gives a contextual view of Lydgate's writing of the Troy Book. Lydgate writes for a more varied target audience than his thirteenth-century source, Guido delle Colonne, and there is a deliberation on the female characters of the Troy Book which promulgates the theory that Lydgate takes a proactive and empathetic interest in women's roles in society. Furthermore Lydgate has never really been accepted as a humanist, and I look at Lydgate's work from a different angle; he is a self-germinating humanist. Lydgate revives antiquity to educate his fifteenth-century audience, and his ambition is to create a memorial for his patron in the vernacular, and enhance his own fame as a poet separate from Chaucer's shadow.