861 resultados para Skype, crittografia, sicurezza, intercettazioni, peer-to-peer.


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This thesis interrogates the construction of fairness to the accused in historic child sexual abuse trials in Ireland. The protection of fairness is a requirement of any trial that claims to adhere to the rule of law. Historic child sexual abuse trials, in which the charges relate to events that are alleged to have taken place decades previously, present serious challenges to the ability of the trial process to safeguard fairness. They are a litmus test of the courts’ commitment to fairness. The thesis finds that in historic abuse trials fairness to the accused has been significantly eroded and that therefore the Irish Courts have failed to respect the core of the rule of law in these most serious of prosecutions. The thesis scrutinises two bodies of case law, both of which deal with the issue of whether evidence should reach the jury. First, it examines the decisions on applications brought by defendants seeking to prohibit their trial. The courts hearing prohibition applications face a dilemma: how to ensure the defendant is not put at risk of an unfair trial, while at the same time recognising that delay in reporting is a defining feature of these cases. The thesis traces the development of the prohibition case law and tracks the shifting interpretations given to fairness by the courts. Second, the thesis examines what fairness means in the superior courts’ decisions regarding the admissibility of the following kinds of evidence, each of which presents particular challenges to the ability of the trial to safeguard fairness: evidence of multiple complainants; evidence of recovered memories and evidence of complainants’ therapeutic records. The thesis finds that in both bodies of case law the Irish courts have hollowed out the meaning of fairness. It makes proposals on how fairness might be placed at the heart of courts’ decisions on admissibility in historic abuse trials. The thesis concludes that the erosion of fairness in historic abuse trials is indicative of a move away from the liberal model of criminal justice. It cautions that unless fairness is prioritised in historic child sexual abuse trials the legitimacy of these trials and that of all Irish criminal trials will be contestable.

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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.

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The aim of this dissertation is to revive the 19th-century thinker Max Stirner’s thought through a critical reexamination of his mistaken legacy as a ‘political’ thinker. The reading of Stirner that I present is one of an ontological thinker, spurred on as much—if not more—by the contents of Hegel’s Phenomenology of Spirit as it is the radical roots that Hegel unintentionally planted. In the first chapter, the role of language in Stirner’s thought is examined, and the problems to which his conception of language seem to give rise are addressed. The second chapter looks at Stirner’s purportedly ‘anarchistic’ politics and finds the ‘anarchist’ reading of Stirner misguided. Rather than being a ‘political’ anarchist, it is argued that we ought to understand Stirner as advocating a sort of ‘ontological’ anarchism in which the very existence of authority is questioned. In the third chapter, I look at the political ramifications of Stirner’s ontology as well as the critique of liberalism contained within it, and argue that the politics implicit in his philosophy shares more in common with the tradition of political realism than it does anarchism. The fourth chapter is dedicated to an examination of Stirner’s anti-humanism, which is concluded to be much different than the ‘anti-humanisms’ associated with other, more famous thinkers, such as Foucault and Heidegger. In the fifth and final chapter, I provide an answer to the question(s) of how, if, and to what extent Friedrich Nietzsche was influenced by Stirner. It is concluded that the complete lack of evidence that Nietzsche ever read Stirner is proof enough to dismiss accusations of plagiarism on Nietzsche’s part, thus emphasizing the originality and singularity of both thinkers.

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Schizophrenia represents one of the world’s most devastating illnesses due to its often lifelong course and debilitating nature. The treatment of schizophrenia has vastly improved over recent decades with the discovery of several antipsychotic compounds; however these drugs are not without adverse effects that must be addressed to maximize their therapeutic value. Newer, atypical, antipsychotics are associated with a compilation of serious metabolic side effects including weight gain, insulin resistance, fat deposition, glucose dysregulation and ensuing co-morbidities such as type II diabetes mellitus. The mechanisms underlying these side effects remain to be fully elucidated and adequate interventions are lacking. Further understanding of the factors that contribute these side effects is therefore required in order to develop effective adjunctive therapies and to potentially design antipsychotic drugs in the future with reduced impact on the metabolic health of patients. We investigated if the gut microbiota represented a novel mechanism contributing to the metabolic dysfunction associated with atypical antipsychotics. The gut microbiota comprises the bacteria that exist symbiotically within the gastrointestinal tract, and has been shown in recent years to be involved in several aspects of energy balance and metabolism. We have demonstrated that administration of certain antipsychotics in the rat results in an altered microbiota profile and, moreover, that the microbiota is required for the full scale of metabolic dysfunction to occur. We have further shown that specific antibiotics can attenuate certain aspects of olanzapine and risperidone–induced metabolic dysfunction, in particular fat deposition and adipose tissue inflammation. Mechanisms underlying this novel link appear to involve energy utilization via expression of lipogenic genes as well as reduced inflammatory tone. Taken together, these data indicate that the gut microbiota is an important factor involved in the myriad of metabolic complications associated with antipsychotic therapy. Furthermore, these data support the future investigation of microbial-based therapeutics for not only antipsychotic-induced weight gain but also for tackling the global obesity epidemic.

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The aim of this research, which focused on the Irish adult population, was to generate information for policymakers by applying statistical analyses and current technologies to oral health administrative and survey databases. Objectives included identifying socio-demographic influences on oral health and utilisation of dental services, comparing epidemiologically-estimated dental treatment need with treatment provided, and investigating the potential of a dental administrative database to provide information on utilisation of services and the volume and types of treatment provided over time. Information was extracted from the claims databases for the Dental Treatment Benefit Scheme (DTBS) for employed adults and the Dental Treatment Services Scheme (DTSS) for less-well-off adults, the National Surveys of Adult Oral Health, and the 2007 Survey of Lifestyle Attitudes and Nutrition in Ireland. Factors associated with utilisation and retention of natural teeth were analysed using count data models and logistic regression. The chi-square test and the student’s t-test were used to compare epidemiologically-estimated need in a representative sample of adults with treatment provided. Differences were found in dental care utilisation and tooth retention by Socio-Economic Status. An analysis of the five-year utilisation behaviour of a 2003 cohort of DTBS dental attendees revealed that age and being female were positively associated with visiting annually and number of treatments. Number of adults using the DTBS increased, and mean number of treatments per patient decreased, between 1997 and 2008. As a percentage of overall treatments, restorations, dentures, and extractions decreased, while prophylaxis increased. Differences were found between epidemiologically-estimated treatment need and treatment provided for those using the DTBS and DTSS. This research confirms the utility of survey and administrative data to generate knowledge for policymakers. Public administrative databases have not been designed for research purposes, but they have the potential to provide a wealth of knowledge on treatments provided and utilisation patterns.

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The desire to obtain competitive advantage is a motivator for implementing Enterprise Resource Planning (ERP) Systems (Adam & O’Doherty, 2000). However, while it is accepted that Information Technology (IT) in general may contribute to the improvement of organisational performance (Melville, Kraemer, & Gurbaxani, 2004), the nature and extent of that contribution is poorly understood (Jacobs & Bendoly, 2003; Ravichandran & Lertwongsatien, 2005). Accordingly, Henderson and Venkatraman (1993) assert that it is the application of business and IT capabilities to develop and leverage a firm’s IT resources for organisational transformation, rather than the acquired technological functionality, that secures competitive advantage for firms. Application of the Resource Based View of the firm (Wernerfelt, 1984) and Dynamic Capabilities Theory (DCT) (Teece and Pisano (1998) in particular) may yield insights into whether or not the use of Enterprise Systems enhances organisations’ core capabilities and thereby obtains competitive advantage, sustainable or otherwise (Melville et al., 2004). An operational definition of Core Capabilities that is independent of the construct of Sustained Competitive Advantage is formulated. This Study proposes and utilises an applied Dynamic Capabilities framework to facilitate the investigation of the role of Enterprise Systems. The objective of this research study is to investigate the role of Enterprise Systems in the Core Dynamic Capabilities of Asset Lifecycle Management. The Study explores the activities of Asset Lifecycle Management, the Core Dynamic Capabilities inherent in Asset Lifecycle Management and the footprint of Enterprise Systems on those Dynamic Capabilities. Additionally, the study explains the mechanisms by which Enterprise Systems sustain the Exploitability and the Renewability of those Core Dynamic Capabilities. The study finds that Enterprise Systems contribute directly to the Value, Exploitability and Renewability of Core Dynamic Capabilities and indirectly to their Inimitability and Non-substitutability. The study concludes by presenting an applied Dynamic Capabilities framework, which integrates Alter (1992)’s definition of Information Systems with Teece and Pisano (1998)’s model of Dynamic Capabilities to provide a robust diagnostic for determining the sustained value generating contributions of Enterprise Systems. These frameworks are used in the conclusions to frame the findings of the study. The conclusions go on to assert that these frameworks are free - standing and analytically generalisable, per Siggelkow (2007) and Yin (2003).

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Natural and human-made disasters cause on average 120,000 deaths and over US$140 billion in damage to property and infrastructure every year, with national, regional and international actors consistently responding to the humanitarian imperative to alleviate suffering wherever it may be found. Despite various attempts to codify international disaster laws since the 1920s, a right to humanitarian assistance remains contested, reflecting concerns regarding the relative importance of state sovereignty vis-à-vis individual rights under international law. However, the evolving acquis humanitaire of binding and non-binding normative standards for responses to humanitarian crises highlights the increasing focus on rights and responsibilities applicable in disasters; although the International Law Commission has also noted the difficulty of identifying lex lata and lex ferenda regarding the protection of persons in the event of disasters due to the “amorphous state of the law relating to international disaster response.” Therefore, using the conceptual framework of transnational legal process, this thesis analyses the evolving normative frameworks and standards for rights-holders and duty-bearers in disasters. Determining the process whereby rights are created and evolve, and their potential internalisation into domestic law and policy, provides a powerful analytical framework for examining the progress and challenges of developing accountable responses to major disasters.

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Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterised by the loss of midbrain dopaminergic neurons from the substantia nigra pars compacta(SNpc), which results in motor, cognitive and psychiatric symptoms. Evidence supports a role for the mitogen-activated protein kinase p38 in the demise of dopaminergic neurons, while mitogen-activated protein kinase phosphatase-1 (MKP-1), which negatively regulates p38 activity, has not yet been investigated in this context. Inflammation may also be associated with the neuropathology of PD due to evidence of increased levels of proinflammatory cytokines such as interleukin-1β (IL-1β) within the SNpc. Because of the specific loss of dopaminergic neurons in a discreet region of the brain, PD is considered a suitable candidate for cell replacement therapy but challenges remain to optimise dopaminergic cell survival and morphological development. The present thesis examined the role of MKP-1 in neurotoxic and inflammatory-induced changes in the development of midbrain dopaminergic neurons. We show that MKP-1 is expressed in dopaminergic neurons cultured from embryonic day (E) 14 rat ventral mesencephalon (VM). Inhibition of dopaminergic neurite growth induced by treatment of rat VM neurons with the dopaminergic neurotoxin 6- hydroxydopamine (6-OHDA) is mediated by p38, and is concomitant with a significant and selective decrease in MKP-1 expression in these neurons. Dopaminergic neurons transfected to overexpress MKP-1 displayed a more complex morphology and contributed to neuroprotection against the effects of 6-OHDA. Therefore, MKP-1 expression can promote the growth and elaboration of dopaminergic neuronal processes and can help protect them from the neurotoxic effects of 6-OHDA. Neural precursor cells (NPCs) have emerged as promising alternative candidates to fetal VM for cell replacement strategies in PD. Here we show that phosphorylated (and thus activated) p38 and MKP-1 are expressed at basal levels in untreated E14 rat VM NPCs (nestin, DCX, GFAP and DAT-positive cells) following proliferation as well as in their differentiated progeny (DCX, DAT, GFAP and βIII-tubulin) in vitro. Challenge with 6-OHDA or IL-1β changed the expression of endogenous phospho-p38 and MKP-1 in these cells in a time-dependent manner, and so the dynamic balance in expression may mediate the detrimental effects of neurotoxicity and inflammation in proliferating and differentiating NPCs. We demonstrate that there was an up-regulation in MKP-1 mRNA expression in adult rat midbrain tissue 4 days post lesion in two rat models of PD; the 6-OHDA medial forebrain bundle (MFB) model and the four-site 6-OHDA striatal lesion model. This was concomitant with a decrease in tyrosine hydroxylase (TH) mRNA expression at 4 and 10 days post-lesion in the MFB model and 10 and 28 days post-lesion in the striatal lesion model. There was no change in mRNA expression of the pro-apoptotic gene, bax and the anti-apoptotic gene, bcl-2 in the midbrain and striatum. These data suggest that the early and transient upregulation of MKP-1 mRNA in the midbrain at 4 days post-6-OHDA administration may be indicative of an attempt by dopaminergic neurons in the midbrain to protect against the neurotoxic effects of 6-OHDA at later time points. Collectively, these findings show that MKP-1 is expressed by developing and adult dopaminergic neurons in the midbrain, and can promote their morphological development. MKP-1 also exerts neuroprotective effects against dopaminergic neurotoxins in vitro, and its expression in dopaminergic neurons can be modulated by inflammatory and neurotoxic insults both in vitro and in vivo. Thus, these data contribute to the information needed to develop therapeutic strategies for protecting midbrain dopaminergic neurons in the context of PD.

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The objective of my Portfolio is to explore the working hypothesis that the organic growth of a firm is governed by the perspectives of individuals and such perspectives are governed by their meaning-making. The Portfolio presents explorations of the transformation of my meaning making and in adopting new practices to support the organic growth of a firm. I use the work of other theorists to transition my understanding of how the world works. This transition process is an essential tool to engage with and understand the perspectives of others and develop a mental capacity to “train one’s imagination to go visiting” (Arendt, 1982; p.43). The Portfolio, therefore, is primarily located in reflective research. Using Kegan’s (1994) approach to Adult Mental Development, and Sowell’s (2007) understanding of the visions which silently shape our thoughts I organise the developments of my meaning making around three transformation pillars of change. In pillar one I seek to transform an unthinking respect for authority and break down a blind pervasiveness of thought within my reasoning process arising from an instinct for attachment and support from others whom I trust. In pillar two I seek to discontinue using autocratic leadership and learn to use the thoughts and contributions of a wider team to make improved choices about uncertain future events. In pillar three I explore the use of a more reflective thinking framework to test the accuracy of my perceptions and apply a high level of integrity in my reasoning process. The transformation of my meaning making has changed my perspectives and in turn my preferred practices to support the organic growth of a firm. I identify from practice that a transformative form of leadership is far more effective that a transactional form of leadership to stimulate the trust and teamwork required to sustain the growth a firm. Creating an environment where one feels free to share thoughts and feelings with others is an essential tool to build a team to critique the thoughts of one other. Furthermore, the entrepreneurial wisdom to grow a firm must come from a wider team, located both inside and outside the boundaries of a firm. No individual or small team has the mental capacity to provide the entrepreneurship required to drive the organic growth of a firm. I address my Portfolio to leaders in organisations who have no considered framework on the best practices required to lead a social organisation. These individuals may have no sense of what they implicitly believe drives social causation and they may have no understanding if their meaning making supports or curtails the practices required to grow a firm. They may have a very limited capacity to think in a logical manner, with the result they are using guesses from their ‘gut’ to make poor judgements in the management of a firm.

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Osteoporosis is a complex skeletal disorder characterized by compromised bone strength. Variation in bone mineral density (BMD) is a contributing factor. The aim of this research as to select informative single nucleotide polymorphisms (SNPs) in potential candidate genes from loci suggestively linked to BMD variation for fine mapping. The gene regulated by oestrogen in breast cancer 1 (GREB1), located at 2p25.1, was selected. GREB1 transcription is initiated early in the oestrogen receptor alpha regulated pathway. There was significant association between GREB1_03 and BMD variation at the lumbar spine and femoral neck (FN) in the discovery cohort. Significant association was observed between GREB1_04 and FN BMD in the replication cohort. The development and differentiation enhancing factor 2, the integrin cytoplasmic domain associated protein 1 and A-disintegrin and metalloprotease 17 were selected due to their respective roles in cell mobility and adhesion. There was no linkage or association observed between the Chr2 cluster SNPs and BMD. Two factors in bone remodelling are the attraction of bone cell precursors and endocrine regulation of the process, primarily through the action of parathyroid hormone (PTH). The C-C chemokine receptor type 3 (CCR3) encodes a CC chemokine receptor expressed in osteoclast precursors. The PTH receptor type 1 (PTHR1) encodes a G-protein coupled receptor for PTH. Association was observed between CCR3 haplotypes and BMD variation at the FN. There was no linkage or association observed between PTHR1 SNPs and BMD variation. Population genetic studies with complex phenotypes endeavour to elucidate the traits genetic architecture. This study presents evidence of association between GREB1 and BMD variation and as such, introduces GREB1 as a novel gene target for osteoporosis genetics studies. It affirms that common genomic variants in PTHR1 are not associated with BMD variation in Caucasians and supports the evidence that CCR3 may be contributing to BMD variation

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Depression is among the leading causes of disability worldwide. Currently available antidepressant drugs have unsatisfactory efficacy, with up to 60% of depressed patients failing to respond adequately to treatment. Emerging evidence has highlighted a potential role for the efflux transporter P-glycoprotein (P-gp), expressed at the blood-brain barrier (BBB), in the aetiology of treatment-resistant depression. In this thesis, the potential of P-gp inhibition as a strategy to enhance the brain distribution and pharmacodynamic effects of antidepressant drugs was investigated. Pharmacokinetic studies demonstrated that administration of the P-gp inhibitors verapamil or cyclosporin A (CsA) enhanced the BBB transport of the antidepressants imipramine and escitalopram in vivo. Furthermore, both imipramine and escitalopram were identified as transported substrates of human P-gp in vitro. Contrastingly, human P-gp exerted no effect on the transport of four other antidepressants (amitriptyline, duloxetine, fluoxetine and mirtazapine) in vitro. Pharmacodynamic studies revealed that pre-treatment with verapamil augmented the behavioural effects of escitalopram in the tail suspension test (TST) of antidepressant-like activity in mice. Moreover, pre-treatment with CsA exacerbated the behavioural manifestation of an escitalopram-induced mouse model of serotonin syndrome, a serious adverse reaction associated with serotonergic drugs. This finding highlights the potential for unwanted side-effects which may occur due to increasing brain levels of antidepressants by P-gp inhibition, although further studies are needed to fully elucidate the mechanism(s) at play. Taken together, the research outlined in this thesis indicates that P-gp may restrict brain concentrations of escitalopram and imipramine in patients. Moreover, we show that increasing the brain distribution of an antidepressant by P-gp inhibition can result in an augmentation of antidepressant-like activity in vivo. These findings raise the possibility that P-gp inhibition may represent a potentially beneficial strategy to augment antidepressant treatment in clinical practice. Further studies are now warranted to evaluate the safety and efficacy of this approach.

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This thesis involved researching normative family discourses which are mediated through educational settings. The traditional family, consisting of father, mother and children all living together in one house is no longer reflective of the home situation of many Irish students (Lunn and Fahey, 2011). My study problematizes the dominant discourses which reflect how family differences are managed and recognised in schools. A framework using Foucauldian post structural critical analysis traces family stratification through the organisation of institutional and interpersonal relations at micro level in four post-primary schools. Standardising procedures such as the suppression of intimate relations between and among teacher and student, as well as the linear ordering of intergenerational relations, such as teacher/student and adult/child are critiqued. Normalising discourses operate in practices such as notes home which presume two parents together. Teacher assumptions about heterosexual two-parent families make it difficult for students to be open about a family setup that is constructed as different to the rest of the schools'. The management of family difference and deficit through pastoral care structures suggests a school-based politics of family adjustment. These practices beg the question whether families are better off not telling the school about their family identity. My thesis will be of interest to educational research and educational policy because it highlights how changing demographics such as family compositions are mis-conceptualised in schools, as well as revealing the changing forms of family governance through regimes such as pastoral care. This analysis allows for the existence of, and a valuing for, alternative modes of family existence, so that future curricular and legal discourses can be challenged in the interest of equity and social justice.

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Hazard perception has been found to correlate with crash involvement, and has thus been suggested as the most likely source of any skill gap between novice and experienced drivers. The most commonly used method for measuring hazard perception is to evaluate the perception-reaction time to filmed traffic events. It can be argued that this method lacks ecological validity and may be of limited value in predicting the actions drivers’ will take to hazards encountered. The first two studies of this thesis compare novice and experienced drivers’ performance on a hazard detection test, requiring discrete button press responses, with their behaviour in a more dynamic driving environment, requiring hazard handling ability. Results indicate that the hazard handling test is more successful at identifying experience-related differences in response time to hazards. Hazard detection test scores were strongly related to performance on a driver theory test, implying that traditional hazard perception tests may be focusing more on declarative knowledge of driving than on the procedural knowledge required to successfully avoid hazards while driving. One in five Irish drivers crash within a year of passing their driving test. This suggests that the current driver training system does not fully prepare drivers for the dangers they will encounter. Thus, the third and fourth studies in this thesis focus on the development of two simulator-based training regimes. In the third study participants receive intensive training on the molar elements of driving i.e. speed and distance evaluation. The fourth study focuses on training higher order situation awareness skills, including perception, comprehension and projection. Results indicate significant improvement in aspects of speed, distance and situation awareness across training days. However, neither training programme leads to significant improvements in hazard handling performance, highlighting the difficulties of applying learning to situations not previously encountered.

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For at least two millennia and probably much longer, the traditional vehicle for communicating geographical information to end-users has been the map. With the advent of computers, the means of both producing and consuming maps have radically been transformed, while the inherent nature of the information product has also expanded and diversified rapidly. This has given rise in recent years to the new concept of geovisualisation (GVIS), which draws on the skills of the traditional cartographer, but extends them into three spatial dimensions and may also add temporality, photorealistic representations and/or interactivity. Demand for GVIS technologies and their applications has increased significantly in recent years, driven by the need to study complex geographical events and in particular their associated consequences and to communicate the results of these studies to a diversity of audiences and stakeholder groups. GVIS has data integration, multi-dimensional spatial display advanced modelling techniques, dynamic design and development environments and field-specific application needs. To meet with these needs, GVIS tools should be both powerful and inherently usable, in order to facilitate their role in helping interpret and communicate geographic problems. However no framework currently exists for ensuring this usability. The research presented here seeks to fill this gap, by addressing the challenges of incorporating user requirements in GVIS tool design. It starts from the premise that usability in GVIS should be incorporated and implemented throughout the whole design and development process. To facilitate this, Subject Technology Matching (STM) is proposed as a new approach to assessing and interpreting user requirements. Based on STM, a new design framework called Usability Enhanced Coordination Design (UECD) is ten presented with the purpose of leveraging overall usability of the design outputs. UECD places GVIS experts in a new key role in the design process, to form a more coordinated and integrated workflow and a more focused and interactive usability testing. To prove the concept, these theoretical elements of the framework have been implemented in two test projects: one is the creation of a coastal inundation simulation for Whitegate, Cork, Ireland; the other is a flooding mapping tool for Zhushan Town, Jiangsu, China. The two case studies successfully demonstrated the potential merits of the UECD approach when GVIS techniques are applied to geographic problem solving and decision making. The thesis delivers a comprehensive understanding of the development and challenges of GVIS technology, its usability concerns, usability and associated UCD; it explores the possibility of putting UCD framework in GVIS design; it constructs a new theoretical design framework called UECD which aims to make the whole design process usability driven; it develops the key concept of STM into a template set to improve the performance of a GVIS design. These key conceptual and procedural foundations can be built on future research, aimed at further refining and developing UECD as a useful design methodology for GVIS scholars and practitioners.

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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.