Phenobarbital reduces EEG amplitude and propagation of neonatal seizures but does not alter performance of automated seizure detection

Objective: Phenobarbital increases electroclinical uncoupling and our preliminary observations suggest it may also affect electrographic seizure morphology. This may alter the performance of a novel seizure detection algorithm (SDA) developed by our group. The objectives of this study were to compare the morphology of seizures before and after phenobarbital administration in neonates and to determine the effect of any changes on automated seizure detection rates. Methods: The EEGs of 18 term neonates with seizures both pre- and post-phenobarbital (524 seizures) administration were studied. Ten features of seizures were manually quantified and summary measures for each neonate were statistically compared between pre- and post-phenobarbital seizures. SDA seizure detection rates were also compared. Results: Post-phenobarbital seizures showed significantly lower amplitude (p < 0.001) and involved fewer EEG channels at the peak of seizure (p < 0.05). No other features or SDA detection rates showed a statistical difference. Conclusion: These findings show that phenobarbital reduces both the amplitude and propagation of seizures which may help to explain electroclinical uncoupling of seizures. The seizure detection rate of the algorithm was unaffected by these changes. Significance: The results suggest that users should not need to adjust the SDA sensitivity threshold after phenobarbital administration.

The role of the community service order and the suspended sentence in Ireland: a judicial perspective

Imprisonment is the most severe penalty utilised by the criminal courts in Ireland. In recent decades the prison population has grown significantly despite expressions both official and public to reduce the use of the sanction. Two other sanctions are available to the Irish sentencer which may be used as a direct and comparable sentence in lieu of a term of imprisonment namely, the community service order and the suspended sentence. The community service order remains under-utilised as an alternative to the custodial sentence. The suspended sentence is used quite liberally but its function may be more closely related to the aim of deterrence rather than avoiding the use of the custodial sentence. Thus the aim of decarceration may not be optimal in practice when either sanction is utilised. The decarcerative effect of either sanction is largely dependent upon the specific purpose which judges invest in the sanction. Judges may also be inhibited in the use of either sanction if they lack confidence that the sentence will be appropriately monitored and executed. The purpose of this thesis is to examine the role of the community service order and the suspended sentence in Irish sentencing practice. Although community service and the suspended sentence present primarily as alternatives to the custodial sentence, the manner in which the judges utilise or fail to utilise the sanctions may differ significantly from this primary manifestation. Therefore the study proceeds to examine the judges' cognitions and expectations of both sanctions to explore their underlying purposes and to reveal the manner in which the judges use the sanctions in practice. To access this previously undisclosed information a number of methodologies were deployed. An extensive literature review was conducted to delineate the purpose and functionality of both sanctions. Quantitative data was gathered by way of sampling for the suspended sentence and the part-suspended sentence where deficiencies were apparent to show the actual frequency in use of that sanction. Qualitative methodologies were used by way of focus groups and semi-structured interviews of judges at all jurisdictional levels to elucidate the purposes of both sanctions. These methods allowed a deeper investigation of the factors which may promote or inhibit such usage. The relative under-utilisation of the community service order as an alternative to the custodial sentence may in part be explained by a reluctance by some judges to equate it with a real custodial sentence. For most judges who use the sanction, particularly at summary level, community service serves a decarcerative function. The suspended sentence continues to be used extensively. It operates partly as a decarcerative penalty but the purpose of deterrence may in practice overtake its theoretical purpose namely the avoidance of custody. Despite ongoing criticism of executive agencies such as the Probation Service and the Prosecution in the supervision of such penalties both sanctions continue to be used. Engagement between the Criminal Justice actors may facilitate better outcomes in the use of either sanction. The purposes for which both sanctions are deployed find their meaning essentially in the practices of the judges themselves as opposed to any statutory or theoretical claims upon their use or purpose.

Investigation of the function of the LNX family of E3 ubiquitin ligases in the nervous system

The Lnx1 (Ligand of Numb protein X 1) and Lnx2 genes belong to a family of PDZ domain-containing RING finger domain E3 ubiquitin ligases. mRNA expression for both genes have been reported in early murine central nervous system. However, there have been limited reports with regards to the expression patterns for both the proteins in vivo. Hence, we have attempted to characterize the significance of these proteins in the context of morphology and physiology of the central nervous system. Through our studies, we have attempted to examine closely the expression of these two genes in the murine central nervous system. We have also looked at novel interacting ligands for both proteins. Interacting partners have been examined with particular relevance to possible roles of their interactions with LNX1 and LNX2 in the functioning of the nervous system. Moreover, we have performed loss-of-function studies by way of creation and characterization of knockout mice.

A policy analysis of key employability interventions for the educationally disadvantaged in further education: Comparative insights for Irish education

The aim of this study is to garner comparative insights so as to aid the development of the discourse on further education (FE) conceptualisation and the relationship of FE with educational disadvantage and employability. This aim is particularly relevant in Irish education parlance amidst the historical ambiguity surrounding the functioning of FE. The study sets out to critically engage with the education/employability/economy link (eee link). This involves a critique of issues relevant to participation (which extends beyond student activity alone to social relations generally and the dialogic participation of the disadvantaged), accountability (which extends beyond performance measures alone to encompass equality of condition towards a socially just end) and human capital (which extends to both collective and individual aspects within an educational culture). As a comparative study, there is a strong focus on providing a way of conceptualising and comparatively analysing FE policy internationally. The study strikes a balance between conceptual and practical concerns. A critical comparative policy analysis is the methodology that structures the study which is informed and progressed by a genealogical method to establish the context of each of the jurisdictions of England, the United States and the European Union. Genealogy allows the use of history to diagnose the present rather than explaining how the past has caused the present. The discussion accentuates the power struggles within education policy practice using what Fairclough calls a strategic critique as well as an ideological critique. The comparative nature of the study means that there is a need to be cognizant of the diverse cultural influences on policy deliberation. The study uses the theoretical concept of paradigmatic change to critically analyse the jurisdictions. To aid with the critical analysis, a conceptual framework for legislative functions is developed so as to provide a metalanguage for educational legislation. The specific contribution of the study, while providing a manner for understanding and progressing FE policy development in a globalized Ireland, is to clear the ground for a more well-defined and critically reflexive FE sector to operate and suggests a number of issues for further deliberation.

The contribution of warlordism to the disintegration of the western Roman army (c. AD 395-480)

My thesis investigates the dynamics behind the changing nature of the leadership of the western Roman army in the fifth century through the concept of ‘warlordism’. I carried this out by analyzing those cases of insubordination and military unrest in the officer class of the western Roman army, which can be shown to be linked to the slow decline of central authority and the imperial office in the period 395-480. My thesis demonstrates that theories of ‘Warlordism’, as developed in social sciences, can be useful for both the late Imperial west as for other eras of ancient history, such as the late Roman republic. Warlordism was a way of continuing politics, if necessary by military means, when commanders found themselves outside the legitimate framework. Unlike the case of usurpation of the imperial office, when there was little hope of achieving permanent recognition and acceptance, it offered insubordinate officers a chance of returning to the ruling imperial regime depending on circumstances and the success of their resistance. I propose that warlordism functioned as an alternative to usurpation, a tool for military dissidence, fuelled by an economy of violence. Contrary to modern warlordism, the warlordism of the fifth century AD represented a transient phase which no imperial commander was willing to prolong indefinitely. At some stage, given the means, warlords in the western Roman army wanted to become part of the imperial echelon again. Yet these alternative methods of violent opposition, and the acquisition of force through private means, ensured the breakdown of the state’s monopoly on violence and the disintegration of centralized armies. What started as an accidental revolution became a new form of military rule.

Echoes of existentialism in the works of Carlos Fuentes

In this thesis I have set out to trace the echoes of existentialism in the work of the Mexican novelist, Carlos Fuentes scrutinizing, in particular, La región más transparente, La muerte de Artemio Cruz and Cambio de piel. In the opening segment of the thesis I outline the essential tenets of existentialist thought and how it became the predominant philosophical and literary movement of the early part of the twentieth-century. Stemming from the work of Sören Kierkegaard in Denmark towards the end of the nineteenth-century, it challenged the arid philosophies of previous generations and provided a new way of looking at man and the human condition. In this opening chapter, I study the works of the more important philosophers in this regard such as Heidegger, Sartre, Jaspers, Marcel, Unamuno, and Ortega y Gasset and show how each in his own way contributed to the further development of the new philosophy. Chapter 2 is concerned with the spread of existentialism to the Latin American continent. In the early part of the twentieth-century, Mexico was emerging from a turbulent revolutionary period and seeking a solution to the fractured nature of its society. The Spanish philosopher, Ortega y Gasset, and the many Spanish intellectuals who sought refuge from Franco’s dictatorship in Mexico, helped to popularise the new philosophy and these lively debates about existentialism served to underpin ideas around mexicanidad or Mexican national identity. Carlos Fuentes was deeply immersed in the debate of his time, positioned as he was as a prominent public intellectual. In La muerte de Artemio Cruz he shows us how great wealth and power are a poor recompense for the loss of love and compassion and lead only to alienation and selfishness. In his other best known novel, La región más transparente, he explores the rise of modern Mexico and its society – an inauthentic society that is corrupted by a scramble for wealth and self-aggrandizement. The final chapter is devoted to the study of Cambio de piel which is concerned with violence and alienation as central pillars of existence. The violence depicted here precipitates a crisis in the human condition and an accompanying sense of alienation. The thesis seeks to establish that existentialism is central not only to Fuentes’s literary concerns but also forms a part of his ethics as an artist.

Cancer associated malnutrition: prevalence of cachexia, sarcopenia and impact on treatment outcomes, survival and health related quality of life

Malnutrition, sarcopenia and cancer cachexia (CC) are prevalent among cancer patients and can have detrimental effects on clinical outcomes such as quality of life (QoL) and overall survival. Cachexia is associated with lower tolerance for chemotherapy, which limits the total dose that can be delivered, the number of symptomatic responses and any survival advantage that might be accrued. Moreover, for the majority who do not respond, cachexia may be exacerbated by systemic chemotherapy, thus increasing the net symptom burden experienced by patients. The multitude of interactions between cancer location, treatments, nutritional status and QoL has never been thoroughly explored in an Irish cancer cohort. The objectives of this thesis were to further understand nutritional status, especially body composition in ambulatory cancer patients and determine the relationship between nutritional status using different assessment criteria and QoL, chemotherapy toxicity and survival among cancer patients undergoing chemotherapy. Results aimed to identify baseline factors that may be predictive of poor outcome, toxicities to chemotherapy and disease-free and overall survival. This thesis broadly divides into two sections. The first section (Chapters 3 & 4) focuses on improving our knowledge of the nutritional status of Irish cancer outpatients using a cross sectional study design. A study of 517 patients referred for chemotherapy was conducted using computed tomography (CT) imaging (body composition) and a survey that documented oncologic data, weight loss (WL) data and QoL data. We revealed that a significant proportion of Irish cancer patients undergoing chemotherapy experience unintentional WL over the previous 6 months (62%), sarcopenia (45%) and CC (43%), and the distribution of WL and nutritional risk were associated with site of primary tumour and treatment intent. Patients that had sarcopenia, nutritional risk, or CC had significantly reduced functional abilities, more symptoms and adverse global QoL. In the second section of this thesis (Chapters 5 & 6) the potential link between developing toxicity to antineoplastic regimens in patients with sarcopenia was conducted by way of retrospective studies. A retrospective serial CT analysis defined the prevalence of sarcopenia in patients with metastatic renal cell carcinoma (mRCC) and metastatic castrate resistant prostate cancer (mCRPC), which was then correlated with dose limiting toxicities of sunitinib and docetaxel respectively. Sarcopenia was prevalent in patients with mRCC and mCRPC, was an occult condition in patients with normal/high BMI, was associated with less treatment days, was a significant predictor of DLT in patients receiving sunitinib and a significant predictor of neutropenia and neurosensory toxicities in patients receiving docetaxel. This thesis attempted to address the underlying research deficiencies in Irish oncology nutritional data at national level. The findings from this thesis have implications for the planning of cancer care interventions and indicate that further research is required to improve nutritional screening, in particular for CC and sarcopenia, in the hope that timely intervention can improve both patient-centered and oncologic outcomes.

The role of transformative thinking and practice in a property entrepreneur's response to the funding crisis since 2008

This portfolio of exploration explores the role of transformative thinking and practice in a property entrepreneur’s response to the financial crisis which swept over Ireland from 2008. The complexity of this challenge and the mental capacity to meet its demands is at the core of the exploration. This inquiry emerged from the challenges the financial crisis presented to my values, beliefs, assumptions, and theories, i.e. the interpretive lens through which I make meaning of my experiences. Given the issue identified, this inquiry is grounded in aspects of theories of constructive developmental psychology, applied developmental science, and philosophy. Integrating and linking these elements to business practice is the applied element of the Portfolio. As the 2008 crisis unfolded I realised I was at the limits of my way of knowing. I came to understand that the underlying structure of a way of knowing is the ‘subject-object relationship’ i.e. what a way of knowing can reflect upon, look at, have perspective on, in other words, make object, as against what is it embedded in, attached to, identified within, or subject to. My goal became enhancing my awareness of how I made meaning and how new insights, which would transform a way of knowing, are created. The focus was on enhancing my practice. This Portfolio is structured into three essays. Essay One reported on my self-reflection and external evaluation out of which emerged my developmental goals. In Essay Two I undertake a reading for change programme in which different meaning making systems were confronted in order to challenge me as a meaning maker. Essay Three reported on my experiment which concerned the question whether it was possible for me as a property entrepreneur, and for others alike, to retain bank finance in the face of the overwhelming objective of the bank to deleverage their balance sheet of property loans. The output of my research can be grouped into General Developmental and Specific Business Implications. Firstly I address those who are interested in a transformational-based response to the challenges of operating in the property sector in Ireland during a crisis. I outline the apparatus of thought that I used to create insight, and thus transform how I thought, these are Awareness, Subject-object separation, Exploring other’s perspectives from the position of incompleteness, Dialectical thinking and Collingwood’s Questioning activity. Secondly I set out my learnings from the crisis and their impact on entrepreneurial behaviour and the business of property development. I identify ten key insights that have emerged from leading a property company through the crisis. Many of these are grounded in common sense, however, in my experience these were, to borrow Shakespeare’s words, “More honor'd in the breach than the observance” in pre Crisis Ireland. Finally I set out a four-step approach for forging a strategy. This requires my peer practitioners to identify (i) what they are subject to, (ii) Assess the Opportunity or challenge in a Systemic Context, (iii) Explore Multiple Perspectives on the opportunity or Challenge with an Orientation to change how you know and (iv) Using the Questioning Activity to create Knowledge. Based on my experience I conclude that transformative thinking and practice is a key enabler for a property entrepreneur, in responding to a major collapse of traditional (bank debt) funding.