The role of the IL-1 type 1 receptor in the life, death and differentiation of adult hippocampal neural precursor cells

Neurogenesis occurs in two distinct regions of the adult brain; the subgranular zone (SGZ) of the dentate gyrus (DG) in the hippocampus, and the subventricular zone (SVZ) lining the lateral ventricles. It is now well-known that adult hippocampal neurogenesis can be modulated by a number of intrinsic and extrinsic factors e.g. local signalling molecules, exercise, environmental enrichment and learning. Moreover, levels of adult hippocampal neurogenesis decrease with age, at least in rodents, and alterations in hippocampal neurogenesis have been reported in animal models and human studies of neuropsychiatric and neurodegenerative conditions. Neuroinflammation is a common pathological feature of these conditions and is also a potent modulator of adult hippocampal neurogenesis. Recently, the orphan nuclear receptor TLX has been identified as an important regulator of adult hippocampal neurogenesis as its expression is necessary to maintain the neural precursor cell (NPC) pool in the adult DG. Likewise, exposure of animals to voluntary exercise has been consistently demonstrated to promote adult hippocampal neurogenesis. Lentivirus (LV)- mediated gene transfer is a useful tool to elucidate gene function and to explore potential therapeutic candidates across an array of conditions as it facilitates sustained gene expression in both dividing and post-mitotic cell populations. Both intrinsic and extrinsic factors are important regulators of adult hippocampal neurogenesis. Examining how these factors are affected by an inflammatory stimulus, and the subsequent effects on adult hippocampal neurogenesis provides important information for the development of novel treatment strategies for neuropsychiatric and neurodegenerative conditions in which adult hippocampal neurogenesis is impaired. The aims of the series of experiments presented in this thesis were to examine the effect of the pro-inflammatory cytokine interleukin-1β (IL-1β) on adult hippocampal NPCs both in vitro and in vivo. In vitro, we have shown that IL-1β reduces proliferation of adult hippocampal NPCs in a dose and time-dependent manner. In addition, we have demonstrated that TLX expression is reduced by IL-1β. Blockade of IL-1β signalling prevented both the IL-1β-induced reduction in cell proliferation and TLX expression. In vivo, we examined the effect of short term and long term exposure to LV-IL-1β in sedentary mice and in mice exposed to voluntary running. We demonstrated that impaired hippocampal neurogenesis is only evident after long term exposure to IL-1β. In mice exposed to voluntary running, hippocampal neurogenesis is significantly increased following short-term but not long-term exposure to running. Moreover, short-term running effectively prevents any IL-1β-induced effects on hippocampal neurogenesis; however, no such effects are seen following long-term exposure to running.

Perceived risk of death in older primary care patients

There is a large gap between life expectancy and healthy life years at age 65. To reduce this gap, it is necessary that people with medical concerns perceived at higher risk of adverse outcomes are readily identified and treated. The same goes for the need to implement prevention plans. The main objectives of this study are to, in a first step, (a) estimate the percentage of medical concerns, (b) identify factors associated with this concern; in a second step, (c) estimate the perceived risk of death, and (d) evaluate the ability of medical concerns to predict this risk. Results show that the existence and severity of medical concerns are crucial in the prediction of perceived risk of death. Early identification of severity of medical concerns and the availability and adequacy of informal caregiving should allow healthcare professionals to promptly initiate an appropriate assessment and treatment of older patients.

A medical study on wireless inertial measurement technology as a tool for identifying patients at risk of death or imminent clinical deterioration

This paper provides a system description and preliminary results for an ongoing clinical study currently being carried out at the Mid-Western Regional Hospital, Nenagh, Ireland. The goal of the trial is to determine if wireless inertial measurement technology can be employed to identify elderly patients at risk of death or imminent clinical deterioration. The system measures cumulative movement and provides a score that will help provide a robust early warning to clinical staff of clinical deterioration. In addition the study examines some of the logistical barriers to the adoption of wearable wireless technology in front-line medical care.

An assessment of health in post-medieval Ireland: ‘One vast Lazar house filled with famine, disease and death���

Three indicators of health and diet were selected to examine the health status in three socioeconomic groups in post-medieval Ireland. The aim was to examine the reliability of traditional skeletal markers of health in highly contextualised populations. The link between socio-economic status and health was examined to determine if traditional linking of poor health with poverty was evident in skeletal samples. The analysis indicated that this was indeed the case and that health was significantly compromised in populations of low socio-economic status. Thus it indicated that status intimately influences the physical body form. Sex was also found to be a major defining factor in the response of an individual to physiological stress. It was also evident that contemporary populations may suffer from different physiological stresses, and their responses to those stresses may differ. Adaptation was a key factor here. This has implications for studies of earlier populations that may lack detailed contextual data in terms of blanket applications of interpretations. The results also show a decline in health from the medieval through to the post-medieval period, which is intimately linked with the immense social changes and all the related effects of these. The socio-economic structure of post-medieval Ireland was a direct result of the British policies in Ireland. The physical form of the Irish may be seen to have occurred as a result of those policies, with the Irish poor in particular suffering substantial health problems, even in contrast to the poor of Britain. This study has enriched the recorded historical narrative of this period of the recent past, and highlights more nuanced narratives may emerge from the osteoarchaeological analysis when sound contextual information is available. It also examines a period in Irish history that, until very recently, had been virtually untouched in terms of archaeological study.

Afterwords: reparative queer death and the contemporary Irish novel, 1960-2000

Given that an extant comprehensive study of homosexuality and the twentieth century Irish novel has yet to produced, this thesis is an attempt at rectifying such a gap in research by way of close textual analysis of writing from the latter half of the century—that is, from 1960-2000. Analysis of seven novels by four male authors – John Broderick, Desmond Hogan, Colm Tóibín and Keith Ridgway – lead to one overarching feature common to all four writers becoming clear: the homosexual or queer is always dying or already ‘dead’. ‘Dead’ is placed in inverted commas here as it is not only biological death that characterises the fate of gay men in the aforementioned literature. In the first instance, such men are also always already ‘dead’—that is, by light of their disenfranchisement as homosexual or queer, they are, in socialized terms, examples of the ‘living’ dead. Secondly, biological death neither fully obliterates the queer body nor its disruptive influence. Consequently, one of the overarching ways in which I read queer death in the late twentieth century Irish novel is through the prism of its reparative ‘afterw(a)ord’. On the one hand, such readings are temporally based (that is, reading from a point beyond the death of the protagonist - or their ‘afterward’); while, on the other hand, such readings are stylistically premised (that is, reading or interpreting the narrative itself as an ‘afterword’). The current project thus constitutes an original contribution to knowledge by establishing variant ways of reading the contemporary Irish novel from the point of view of the queer ‘unliving’. In assessing such heterogeneous aspects of contemporary queer death, the project a) contributes to recent, largely Anglo-American-based literary theoretical research on the queer and the eschatological, and b) provides a more contemporized literary base upon which future research can uncover a continuum of Irish queer writing in the twentieth century, one concerned with writing prior to 1960 and not limited to writing my men, in which death and same-sex desire are at parallel angles to one another.

Totality of experience: sound, music and mythology in Gus Van Sant’s “Death Quartet”

Reflecting on Gus Van Sant’s films Gerry (2003) Elephant (2004) and Last Days (2005), the director’s long-term sound-designer Leslie Shatz observed that “You have to get into the totality of the experience and not just the dialogue”. Shatz’s comment expresses something fundamental about the experimental approach to cinema and to soundscapes undertaken by Van Sant in these three films, unofficially known as the “Death Trilogy”. This thesis contends that Van Sant makes deliberate aesthetic choices which do indicate a distinctly “auteurist” leaning. However, I also argue that intertextual elements, prior knowledge, and audience participation in meaningmaking enhance the experience of, and reveal the nuances in, the soundtracks themselves. This thesis aims to contribute to a growing body of work within filmmusic scholarship concerned with resisting a traditional bias in the field: that film music should be understood as a means of characterisation and as emotional signifier. The films of the “Death Quartet”, which includes Paranoid Park (2007), I believe, offer fertile ground on which to explore these new approaches. It is my contention that these films deconstruct the traditional approach to soundtracking and the relationship between soundtrack and character, and that only an approach sensitive to the aesthetic and philosophical functions of music and sound can adequately acknowledge their unique cinematic qualities.