Gambling and violence in a nationally representative sample of UK men

The relationship between violence and problem gambling in general population samples is under-researched and requires further attention to inform treatment and prevention efforts. We investigated the relationship between gambling problems and violence among men and sought to determine if the link can be accounted for by mental disorders, alcohol and drug dependence and impulsivity.

Bridge-vehicle interaction for structural health monitoring: potentials, applications, and limitations

Structural Health Monitoring (SHM) is an integral part of infrastructure maintenance and management systems due to socio-economic, safety and security reasons. The behaviour of a structure under vibration depends on structure characteristics. The change of structure characteristics may suggest the change in system behaviour due to the presence of damage(s) within. Therefore the consistent, output signal guided, and system dependable markers would be convenient tool for the online monitoring, the maintenance, rehabilitation strategies, and optimized decision making policies as required by the engineers, owners, managers, and the users from both safety and serviceability aspects. SHM has a very significant advantage over traditional investigations where tangible and intangible costs of a very high degree are often incurred due to the disruption of service. Additionally, SHM through bridge-vehicle interaction opens up opportunities for continuous tracking of the condition of the structure. Research in this area is still in initial stage and is extremely promising. This PhD focuses on using bridge-vehicle interaction response for SHM of damaged or deteriorating bridges to monitor or assess them under operating conditions. In the present study, a number of damage detection markers have been investigated and proposed in order to identify the existence, location, and the extent of an open crack in the structure. The theoretical and experimental investigation has been conducted on Single Degree of Freedom linear system, simply supported beams. The novel Delay Vector Variance (DVV) methodology has been employed for characterization of structural behaviour by time-domain response analysis. Also, the analysis of responses of actual bridges using DVV method has been for the first time employed for this kind of investigation.

Aspects of the biology of Mya arenaria and Ensis spp. (Mollusca; Bivalvia) in the Irish Sea and adjacent areas

This study was undertaken to investigate the general biology, including the reproductive cycle and health status, of two clam taxa in Irish waters, with particular reference to the Irish Sea area. Monthly samples of the soft shell clam, Mya arenaria, were collected from Bannow Bay, Co. Wexford, Ireland, for sixteen months, and of the razor clam, Ensis spp. from the Skerries region (Irish Sea) between June 2010 and September 2011. In 2010, M. arenaria in Bannow Bay matured over the summer months, with both sexes either ripe or spawning by August. The gonads of both sexes of E. siliqua developed over autumn and winter 2010, with the first spawning individuals being recorded in January 2011. Two unusually cold winters, followed by a warmer than average spring, appear to have affected M. arenaria and E. siliqua gametogenesis at these sites. It was noted that wet weight of E. siliqua dropped significantly in the summer of both 2010 and 2011, after spawning, which may impact on the economic viability of fishing during this period. Additional samples of M. arenaria were collected at Flaxfort (Ireland), and Ensis spp. at Oxwich (Wales), and the pathology of all clams was examined using both histological and molecular methods. No pathogenic conditions were observed in M. arenaria while Prokaryote inclusions, trematode parasites, Nematopsis spp. and inflammatory pathologies were observed at low incidences in razor clams from Ireland but not from Wales; the first time these conditions have been reported in Ensis spp. in northern European waters. Mya arenaria from sites in Europe and eastern and western North America were investigated for genetic variation using both mitochondrial (cytochrome oxidase I (COI) and 16S ribosomal RNA genes) and nuclear markers (10 microsatellite loci). Both mitochondrial CO1 and all nuclear markers showed reduced levels of variation in certain European samples, with significant differences in haplotype and allelic composition between most samples, particularly those from the two different continents, but with the same common haplotypes or alleles throughout the range. The appearance of certain unique rare haplotypes and microsatellite alleles in the European samples suggest a complicated origin involving North American colonization but also possible southern European Pleistocene refugia. Specimens of Ensis spp. were obtained from five coastal areas around Ireland and Wales and species-specific PCR primers were used to amplify the internal transcribed spacer region 1 (ITS1) and the mitochondrial DNA CO1 gene and all but 15 razor clams were identified as Ensis siliqua. Future investigations should focus on continued monitoring of reproductive biology and pathology of the two clam taxa (in particular, to assess the influence of environmental change), and on genetics of southern European M. arenaria and sequencing the CO1 gene in Ensis individuals to clarify species identity

Molecular and cellular aspects of the SREBP pathway

The SREBP (sterol response element binding proteins) transcription factors are central to regulating de novo biosynthesis of cholesterol and fatty acids. The SREBPs are regulated by retention or escape from the ER to the Golgi where they are proteolytically cleaved into active forms. The SREBP cleavage activating protein (SCAP) and the INSIG proteins are essential in this regulatory process. The aim of this thesis is to further characterise the molecular and cellular aspects surrounding regulation of SREBP processing. SREBP and SCAP are known to interact via their carboxy-terminal regulatory domains (CTDs) but this interaction is poorly characterised. Significant steps were achieved in this thesis towards specific mapping of the interaction site. These included cloning and over expression and partial purification of tagged SREBP1 and SREBP2 CTDs and probing of a SCAP peptide array with the CTDs. Results from the SREBP2 probing were difficult to interpret due to insolubility issues with the protein, however, probing with SREBP1 revealed five potential binding sites which were detected reproducibly. Further research is necessary to overcome SREBP2 insolubility issues and to confirm the identified SREBP1 interaction site(s) on SCAP. INSIG1 has a central role in regulating SREBP processing and in regulating stability of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), a rate limiting enzyme in cholesterol biosynthesis. There are two protein isoforms of human INSIG1 produced through the use of two in-frame alternative start sites. Bioinformatic analysis indicated that the presence of two in-frame start sites within the 5-prime region of INSIG1 mRNA is highly conserved and that production of two isoforms of INSIG1is likely a conserved event. Functional differences between these two isoforms were explored. No difference in either the regulation of SREBP processing or HMGCR degradation between the INSIG1 isoforms was observed and the functional significance of the two isoforms is as yet unclear. The final part of this thesis focused on enhancing the cytotoxicity of statins by targeted inhibition of SREBP processing by oxysterols. Statins have significant potential as anti-cancer agents as they inhibit the activity of HMGCR leading to a deficiency in mevalonate which is essential for cell survival. The levels of HMGCR fluctuate widely due to cholesterol feedback of SREBP processing. The relationship between sterol feedback and statin mediated cell death was investigated in depth in HeLa cells. Down regulation of SREBP processing by sterols significantly enhanced the efficacy of statin mediated cell death. Investigation of sterol feedback in additional cancer cell lines showed that sterol feedback was absent in cell lines A- 498, DU-145, MCF-7 and MeWo but was present in cell lines HT-29, HepG2 and KYSE-70. In the latter inhibition of SREBP processing using oxysterols significantly enhanced statin cytotoxicity. The results indicate that this approach is valid to enhance statin cytotoxicity in cancer cells, but may be limited by deregulation of SREBP processing and off target effects of statins, which were observed for some of the cancer cell lines screened.

Health care and neoliberalism in Ireland: withholding the gift and corrupting the social contract

The health of a nation tells much about the nature of a social contract between citizen and state. The way that health care is organised, and the degree to which it is equitably accessible, constitutes a manifestation of the effects of moments and events in that country's history. Using four case studies, this thesis uses a historical genealogical approach to explain the evolution of Ireland's particular version of health care provision. The total social fact of the gift relationship, central to all human relations, will be used to form a theoretical and conceptual framework on which to build an analysis of Ireland's health and welfare conditions. Additionally, social contract theory will enable an examination of the role of solidarity in relation to social expectations around health care provision. Through the analysis of these cases, the complex matrix of the influential forces that have shaped current conditions are exposed and revealed, enabling a critical understanding of the extent of acquiescence to the inequitable system that arguably exists. The vulnerability of citizens in need of care to the external and global effects of market forces and neoliberalism, therefore, becomes central to any argument for state-provided health and welfare. The hegemony of such forces can be seen to influence the manner in which the idea of individual self-reliance, in place of collective solidarity, is conceptualised and subsequently infiltrated into a range of aspects of the social world. For example, the particular discourse of the market and of economic concerns succeeds in shaping understandings of responsibilities around central areas of health and welfare. Similarly the 'possessor principle' can be seen to be misplaced within the context of health and social care, but yet has become normalised within this discourse. Within this matrix of complex influencing factors, the welfare state struggles to impose a balance between market values and social values. Responsibilities of the state to support and compensate its citizens for the ills of the market have become devalued, as the core values of classical liberalism have become distorted beyond recognition, leaving instead bare neoliberal concerns. This thesis traces the genealogical origins of this transition within the recent history of Irish health care and thereby reveals the embedding of individualism in place of solidarity, the on going reneging of the social contract and the corruption of the gift relationship.

A health status survey of clams, Mya arenaria and Ensis siliqua, in the Irish Sea

The soft shell clam, Mya arenaria, and the razor clam, Ensis siliqua, are widely distributed in Irish waters. Though the reproductive biology and other aspects of the physiology of these species has been previously investigated, little or no data are currently available on their health status. As this knowledge is essential for correct management of a species, M. arenaria and E. siliqua were examined to assess their current health status using histological and molecular methods, over a period of sixteen months. No pathogens or disease were observed in M. arenaria, and low incidences of Prokaryote inclusions, trematode parasites, Nematopsis spp. and eosinophilic bodies were recorded in razor clams for the first time in Northern European waters.