The Irish credit union movement: member participation and organisational effectiveness

This thesis explores the relationship between organisational effectiveness and member participation in Irish credit unions. It is hypothesised that a positive relationship exists between both variables. Co-operative literature suggests that co-operatives require the involvement of the members in identifying and meeting their own needs in order to be effective organisations. Previous research studies into the issue across a variety of organisational types have shown mixed results. Related research into credit unions is sparse. The primary research undertaken is both quantitative and qualitative in approach. Organisational effectiveness is examined in both quantitative and qualitative terms. Member participation, being an organisational process, is examined in qualitative terms. Indicators of organisational effectiveness, specific to credit unions, are drawn up and form a framework through which effectiveness is examined. A typology and indicators of member participation are also developed and form a framework through which member participation is examined. The case study method is used primarily, to examine organisational effectiveness and member participation in Irish credit unions. A case study of a theoretical credit union, which is based on a composite of good practice in credit unions in Ireland and internationally, is also drawn up to develop the analysis further. The case studies allow an analysis of both organisational effectiveness and member participation, as well as an exploration of the relationship between the two. The findings support the hypothesis that there is a direct relationship between the two variables. In order to be effective, credit unions must involve their members in identifying their needs and in designing services to meet these needs. At present, they do not do this to any large extent. In order to continue to meet the needs of their members and to compete in the financial services sector, credit unions will need to find ways of involving members, drawing on good practice in other co-operatives. This will be critical to their continued success.

Synthetic and mechanistic aspects of the reactions of α-diazosulfoxides

The research described in this thesis focuses, principally, on synthesis of stable α-diazosulfoxides and investigation of their reactivity under various reaction conditions (transition-metal catalysed, photochemical, thermal and microwave) with a particular emphasis on the reactive intermediates and mechanistic aspects of the reaction pathways involved. In agreement with previous studies carried out on these compounds, the key reaction pathway of α-diazosulfoxides was found to be hetero-Wolff rearrangement to give α-oxosulfine intermediates. However, a competing reaction pathway involving oxygen migration from sulfur to oxygen was also observed. Critically, isomerisation of α-oxosulfine stereoisomers was observed directly by 1H NMR spectroscopy in this work and this observation accounts for the stereochemical outcomes of the various cycloaddition reactions, whether carried out with in situ trapping or with preformed solutions of sulfines. Furthermore, matrix isolation experiments have shown that electrocyclisation of α-oxosulfines to oxathiiranes takes place and this verifies the proposed mechanisms for enol and disulfide formation. The introductory chapter includes a brief literature review of the synthesis and reactivity of α-diazosulfoxides prior to the commencement of research in this field by the Maguire group. The Wolff rearrangement is also discussed and the characteristic reactions of a number of reactive intermediates (sulfines, sulfenes and oxathiiranes) are outlined. The use of microwave-assisted organic synthesis is also examined, specifically, in the context of α-diazocarbonyl compounds as substrates. The second chapter describes the synthesis of stable monocyclic and bicyclic lactone derivatives of α-diazosulfoxides from sulfide precursors according to established experimental procedures. Approaches to precursors of ketone and sulfimide derivatives of α-diazosulfoxides are also described. The third chapter examines the reactivity of α-diazosulfoxides under thermal, microwave, rhodium(II)-catalysed and photochemical conditions. Comparison of the results obtained under thermal and microwave conditions indicates that there was no evidence for any effect, other than thermal, induced by microwave irradiation. The results of catalyst studies involving several rhodium(II) carboxylate and rhodium(II) carboxamidate catalysts are outlined. Under photochemical conditions, sulfur extrusion is a significant reaction pathway while under thermal or transition metal catalysed conditions, oxygen extrusion is observed. One of the most important observations in this work was the direct spectroscopic observation (by 1H NMR) of interconversion of the E and Z-oxosulfines. Trapping of the α-oxosulfine intermediates as cycloadducts by reaction with 2,3-dimethyl-1,3-butadiene proved useful both synthetically and mechanistically. As the stereochemistry of the α-oxosulfine is retained in the cycloadducts, this provided an ideal method for characterisation of this key feature. In the case of one α-oxosulfine, a novel [2+2] cycloaddition was observed. Preliminary experiments to investigate the reactivity of an α-diazosulfone under rhodium(II) catalysis and microwave irradiation are also described. The fourth chapter describes matrix isolation experiments which were carried out in Rühr Universität, Bochum in collaboration with Prof. Wolfram Sander. These experiments provide direct spectroscopic evidence of an α-oxosulfine intermediate formed by hetero-Wolff rearrangement of an α-diazosulfoxide and subsequent cyclisation of the sulfine to an oxathiirane was also observed. Furthermore, it was possible to identify which stereoisomer of the α-oxosulfine was present in the matrix. A preliminary laser flash photolysis experiment is also discussed. The experimental details, including all spectral and analytical data, are reported at the end of each chapter. The structural interpretation of 1H NMR spectra of the cycloadducts, described in Chapter 3, is discussed in Appendix I.

The senior female international managerial career move: a qualitative study in a European context

Research investigating the position of women in management has, largely, been confined within national boundaries. Over the last fifteen years, empirical studies of women in international management have been undertaken, predominantly in North America. In this research field, many questions remain unanswered or have been only partially addressed. The particular focus of this study is on the senior female international managerial career move in Europe — a relatively unexplored area. Fifty senior female expatriate managers were interviewed, representing a wide range of industry and service sectors. The study, for the first time, assesses an exclusively senior sample of female managers who have made at least one international career move. This study of senior females in international management makes a theoretical contribution, not only to the analysis of gender and international human resource management, but also to wider debates within the contemporary women in management and career theory literatures. The aims of the study were to develop an understanding of the senior female international career move in a European context in order to more fully understand both the covert and overt barriers that may limit women’s international career opportunities. The results of the study show that the senior international career move has largely been developed along a linear male model of career progression, a development which, taken together with gender disparity both in organisations and family responsibilities, frequently prevents women employees from reaching senior managerial positions. The study proposes a model of the senior female international managerial career move, thereby contributing primarily to the international human resource management literature. The implications of the study for research literatures in women in management and career theory are also explored and a future research agenda developed.

An investigation of the utilisation of health impact assessments (HIAs) in Irish public policy making

It is the aim of this thesis to investigate Health Impact Assessment (HIA) use in public policy formulation in Northern Ireland and in the Republic of Ireland. The influences affecting the use of HIAs will be examined in this study. Four case studies, where HIA has been conducted, will be used for research analysis. This includes HIAs conducted on traffic and transport in Dublin, Traveller accommodation in Donegal, a draft air quality action plan in Belfast and on a social housing regeneration project in Derry. HIA aims to identify possible intended and unintended consequences that a project, policy or programme will have on the affected population’s health. Although it has been acknowledged as a worthwhile tool to inform decision-makers, the extent to which it is used in policy in Ireland is subject to scrutiny. A theoretical framework, drawing from institutionalist, impact assessment and knowledge utilisation theories and schools of literature, underpin this study. The investigation involves an examination of the unit of analysis which consists of the HIA steering groups. These are made up of local authority decision makers, statutory health practitioners and community representatives. The overarching structure and underlying values which are hypothesized as present in each HIA case are investigated in this research. Chapters 2 and 3 outline the main literature in the area which includes theories from the public health and health promotion paradigm, the policy sciences and impact assessment techniques. Chapter 4 describes the methodology in this research which is a multiple case study design. This is followed by an analysis of the cases and then concludes with practical recommendations for HIA in Ireland and theoretical conclusions of the research.

Equal citizenship for a new society? An analysis of training and employment opportunities for republican ex-prisoners in Belfast

Previous research evidence appears to suggest that while they suffer from similiar socio-economic problems to the wider nationalist community, the problems for republican ex-prisoners seem to be on a greater scale. The primary objective of this research was to investigate the current obstacles facing republication ex-prisoners in training and employment and to make proposals for change.

Investigating the influence of the sulfur oxidation state on solid state conformation

Design, synthesis and structural characterization of a series of diphenylacetylene derivatives bearing organosulfur, amide and amine moieties has been achieved in which the molecular conformation is controlled through variation of the hydrogen bond properties on alteration of the oxidisation level of sulfur.

Mapping the gene for autosomal dominant restless legs syndrome in an Irish family

Restless Legs Syndrome (RLS) is a common neurological disorder affecting nearly 15% of the general population. Ironically, RLS can be described as the most common condition one has never heard of. It is usually characterised by uncomfortable, unpleasant sensations in the lower limbs inducing an uncontrollable desire to move the legs. RLS exhibits a circadian pattern with symptoms present predominantly in the evening or at night, thus leading to sleep disruption and daytime somnolence. RLS is generally classified into primary (idiopathic) and secondary (symptomatic) forms. Primary RLS includes sporadic and familial cases of which the age of onset is usually less than 45 years and progresses slowly with a female to male ratio of 2:1. Secondary forms often occur as a complication of another health condition, such as iron deficiency or thyroid dysfunction. The age of onset is usually over 45 years, with an equal male to female ratio and more rapid progression. Ekbom described the familial component of the disorder in 1945 and since then many studies have been published on the familial forms of the disorder. Molecular genetic studies have so far identified ten loci (5q, 12q, 14p, 9p, 20p, 16p, 19p, 4q, 17p). No specific gene within these loci has been identified thus far. Association mapping has highlighted a further five areas of interest. RLS6 has been found to be associated with SNPs in the BTBD9 gene. Four other variants were found within intronic and intergenic regions of MEIS1, MAP2K5/LBXCOR1, PTPRD and NOS1. The pathophysiology of RLS is complex and remains to be fully elucidated. Conditions associated with secondary RLS, such as pregnancy or end-stage renal disease, are characterised by iron deficiency, which suggests that disturbed iron homeostasis plays a role. Dopaminergic dysfunction in subcortical systems also appears to play a central role. An ongoing study within the Department of Pathology (University College Cork) is investigating the genetic characteristics of RLS in Irish families. A three generation RLS pedigree RLS3002 consisting of 11 affected and 7 unaffected living family members was recruited. The family had been examined for four of the known loci (5q, 12q, 14p and 9p) (Abdulrahim 2008). The aim of this study was to continue examining this Irish RLS pedigree for possible linkage to the previously described loci and associated regions. Using informative microsatellite markers linkage was excluded to the loci on 5q, 12q, 14p, 9p, 20p, 16p, 19p, 4q, 17p and also within the regions reported to be associated with RLS. This suggested the presence of a new unidentified locus. A genome-wide scan was performed using two microsatellite marker screening sets (Research Genetics Inc. Mapping set and the Applied Biosystems Linkage mapping set version 2.5). Linkage analysis was conducted under an autosomal dominant model with a penetrance of 95% and an allele frequency of 0.01. A maximum LOD score of 3.59 at θ=0.00 for marker D19S878 indicated significant linkage on chromosome 19p. Haplotype analysis defined a genetic region of 6.57 cM on chromosome 19p13.3, corresponding to 2.5 Mb. There are approximately 100 genes annotated within the critical region. Sequencing of two candidate genes, KLF16 and GAMT, selected on the assumed pathophysiology of RLS, did not identify any sequence variant. This study provides evidence of a novel RLS locus in an Irish pedigree, thus supporting the picture of RLS as a genetically heterogeneous trait.

Hospital clinicians information behaviour and attitudes towards the 'Clinical Informationist': an Irish survey

Background: Hospital clinicians are increasingly expected to practice evidence-based medicine (EBM) in order to minimize medical errors and ensure quality patient care, but experience obstacles to information-seeking. The introduction of a Clinical Informationist (CI) is explored as a possible solution. Aims:  This paper investigates the self-perceived information needs, behaviour and skill levels of clinicians in two Irish public hospitals. It also explores clinicians perceptions and attitudes to the introduction of a CI into their clinical teams. Methods: A questionnaire survey approach was utilised for this study, with 22 clinicians in two hospitals. Data analysis was conducted using descriptive statistics. Results: Analysis showed that clinicians experience diverse information needs for patient care, and that barriers such as time constraints and insufficient access to resources hinder their information-seeking. Findings also showed that clinicians struggle to fit information-seeking into their working day, regularly seeking to answer patient-related queries outside of working hours. Attitudes towards the concept of a CI were predominantly positive. Conclusion: This paper highlights the factors that characterise and limit hospital clinicians information-seeking, and suggests the CI as a potentially useful addition to the clinical team, to help them to resolve their information needs for patient care.

An investigation of innovation and knowledge creation in virtual worlds

The Internet and World Wide Web have had, and continue to have, an incredible impact on our civilization. These technologies have radically influenced the way that society is organised and the manner in which people around the world communicate and interact. The structure and function of individual, social, organisational, economic and political life begin to resemble the digital network architectures upon which they are increasingly reliant. It is increasingly difficult to imagine how our ‘offline’ world would look or function without the ‘online’ world; it is becoming less meaningful to distinguish between the ‘actual’ and the ‘virtual’. Thus, the major architectural project of the twenty-first century is to “imagine, build, and enhance an interactive and ever changing cyberspace” (Lévy, 1997, p. 10). Virtual worlds are at the forefront of this evolving digital landscape. Virtual worlds have “critical implications for business, education, social sciences, and our society at large” (Messinger et al., 2009, p. 204). This study focuses on the possibilities of virtual worlds in terms of communication, collaboration, innovation and creativity. The concept of knowledge creation is at the core of this research. The study shows that scholars increasingly recognise that knowledge creation, as a socially enacted process, goes to the very heart of innovation. However, efforts to build upon these insights have struggled to escape the influence of the information processing paradigm of old and have failed to move beyond the persistent but problematic conceptualisation of knowledge creation in terms of tacit and explicit knowledge. Based on these insights, the study leverages extant research to develop the conceptual apparatus necessary to carry out an investigation of innovation and knowledge creation in virtual worlds. The study derives and articulates a set of definitions (of virtual worlds, innovation, knowledge and knowledge creation) to guide research. The study also leverages a number of extant theories in order to develop a preliminary framework to model knowledge creation in virtual worlds. Using a combination of participant observation and six case studies of innovative educational projects in Second Life, the study yields a range of insights into the process of knowledge creation in virtual worlds and into the factors that affect it. The study’s contributions to theory are expressed as a series of propositions and findings and are represented as a revised and empirically grounded theoretical framework of knowledge creation in virtual worlds. These findings highlight the importance of prior related knowledge and intrinsic motivation in terms of shaping and stimulating knowledge creation in virtual worlds. At the same time, they highlight the importance of meta-knowledge (knowledge about knowledge) in terms of guiding the knowledge creation process whilst revealing the diversity of behavioural approaches actually used to create knowledge in virtual worlds and. This theoretical framework is itself one of the chief contributions of the study and the analysis explores how it can be used to guide further research in virtual worlds and on knowledge creation. The study’s contributions to practice are presented as actionable guide to simulate knowledge creation in virtual worlds. This guide utilises a theoretically based classification of four knowledge-creator archetypes (the sage, the lore master, the artisan, and the apprentice) and derives an actionable set of behavioural prescriptions for each archetype. The study concludes with a discussion of the study’s implications in terms of future research.

Vulnerability or resilience? Psycho-social factors associated with deliberate self-harm among adolescents

Background: Deliberate self-harm (DSH) is common among adolescents in Ireland and internationally. Psychological factors, negative life events and lifestyle factors have been found to be associated with self-harm in this group. However, large scale population-based studies of adolescent selfharm and its correlates have been lacking, and internationally a standardised methodology was needed to facilitate comparative studies. The focus on vulnerability which has been prevalent in this field has meant that research has failed to examine resilient adaptation among at-risk adolescents. Method: Data were obtained from a cross-sectional school-based study conducted in Ireland and in each of the six other centres which participated in the Child and Adolescent Self-harm in Europe (CASE) study. In Ireland, 3,881 adolescents in 39 schools in completing the anonymous questionnaire, while across all 7 centres, over 30,000 young people participated. Data were gathered on health and lifestyle, self-harm thoughts and behaviour, a wide range of life events, psychological characteristics (anxiety and depressive symptoms, self-esteem, impulsivity and coping style), and support available to young people. Results: This thesis reports the findings of the Irish CASE centre as well as one international study. The factors associated with DSH among Irish adolescents differed by gender, but among both genders drug use and knowing a friend who had engaged in self-harm were associated with DSH. Among Irish boys, strong associations were found between bullying and poor mental health and DSH. Among boys who had been bullied, psychological and school factors were associated with DSH, while family support was protective. Links between stressful life events, psychological characteristics and DSH within the international CASE sample were examined. Increased history of self-harm thoughts and acts was associated with greater depression, anxiety and impulsivity, lower self esteem and an increased prevalence of ten different negative life events, supporting the hypothesis of a “dose-response” relationship between these risk factors and the self-harm process. Associations between coping style, mental health factors (depressive symptoms, anxiety and self-esteem) and self-harm were examined among Irish adolescents. Emotion-oriented coping was strongly associated with poorer mental health and self-harm thoughts and acts. A mediating effect of emotion-oriented coping on associations between mental health factors and DSH was found for both genders and between problem-oriented coping and mental health factors for girls. Similar mediating effects of coping style were found when risk of self-harm thoughts was examined. Resilient adaptation among adolescents exposed to suicidal behaviour of others was examined. Self-harm thoughts were common in these adolescents. Among those exposed to suicidal behaviour of others, vulnerability factors were drug use and higher levels of anxiety among boys, while for girls drug use, bullying and abuse were vulnerability factors, while resilience was associated with higher self-esteem and use of problem-oriented coping. Conclusion: These findings can aid in the identification of young people at risk of self-harm in the school setting and highlight the importance of mental health, peer-related and lifestyle factors in the development of DSH. High-risk groups of young people such as bullying victims and those exposed to suicidal behaviour of others have distinctive profiles of risk factors which differ from those of their peers. Findings relating to the importance of positive coping skills can inform positive mental health programmes, many of which aim to enhance life skills and build resilience among young people. Knowledge of the factors associated with positive adaptation among at-risk adolescents can inform prevention efforts among this group.

Politically motivated former prisoner groups: community activism and conflict transformation

Aims and objectives: This study represents the first sustained quantitative and qualitative attempt to involve both Republicans and Loyalists in an investigation of the impact of imprisonment and the role of politically motivated former prisoners in the process of conflict transformation in Northern Ireland. The overall aim of the project is to examine the ways in which groups of former prisoners are involved in peace-building and conflict transformation work and to evaluate the constraints and impediments placed upon their activities by the effects of the imprisonment process, politically motivated release and residual criminalisation. In pursuing the evaluation of the role of politically motivated former prisoners working within and without their own communities, the research has six specific objectives: To trace the evolution and development of former prisoner groups; To evaluate the impacts of imprisonment and release on the personal lives of former prisoners; To assess the constraints imposed on former prisoners as agents of change by the residual criminalisation arising from their status; To determine the potential of the former prisoner community in challenging intra-community tensions and evaluate their potential and actual contribution to conflict transformation at the inter-community level; To compare and contrast the effectiveness of Loyalist and Republican former prisoners as agents of change within their own communities; To explore the notion of former prisoners as agents of social and communal transformation within broader political processes through grounding the knowledge and practical experience of the former prisoner community within the broader conceptual context of conflict transformation.

Understanding teacher collaboration in disadvantaged urban primary schools: uncovering practices that foster professional learning communities

This study is set in the context of disadvantaged urban primary schools in Ireland. It inquires into the collaborative practices of primary teachers exploring how class teachers and support teachers develop ways of working together in an effort to improve the literacy and numeracy levels of their student. Traditionally teachers have worked in isolation and therefore ‘collaboration’ as a practice has been slow to permeate the historically embedded assumption of how a teacher should work. This study aims to answer the following questions. 1). What are the dynamics of teacher collaboration in disadvantaged urban primary schools? 2). In what ways are teacher collaboration and teacher learning related? 3). In what ways does teacher collaboration influence students’ opportunities for learning? In answering these research questions, this study aims to contribute to the body of knowledge pertaining to teacher learning through collaboration. Though current policy and literature advocate and make a case for the development of collaborative teaching practices, key studies have identified gaps in the research literature in relation to the impact of teacher collaboration in schools. This study seeks to address some of those gaps by establishing how schools develop a collaborative environment and how teaching practices are enacted in such a setting. It seeks to determine what skills, relationships, structures and conditions are most important in developing collaborative environments that foster the development of professional learning communities (PLCs). This study uses a mixed method research design involving a postal survey, four snap-shot case studies and one in depth case study in an effort to establish if collaborative practice is a feasible practice resulting in worthwhile benefits for both teachers and students.

Molecular analysis of virulence mechanisms associated with adherent-invasive Escherichia coli (AIEC)

Crohn's Disease (CD) is a chronic inflammatory bowel disease of unknown etiology. Recent work has shown that a new pathotype of Escherichia coli, Adherent Invasive E. coli (AIEC) may be associated with CD. AIEC has been shown to adhere to and invade epithelial cells and to replicate within macrophages (together this is called the AIEC phenotype). In this thesis, the AIEC phenotype of 84 E. coli strains were determined in order to identify the prevalence of this phenotype within the E. coli genus. This study showed that a significant proportion of E. coli strains (approx. 5%) are capable of adhering to and invading epithelial cells and undergoing intramacrophage replication. Moreover, the results presented in this study indicate a correlation between survival in macrophage and resistance to grazing by amoeba supporting the coincidental evolution hypothesis that resistance to amoebae could be a driving force in the evolution of pathogenicity in some bacteria, such as AIEC. In addition, this study has identified an important regulatory role for the CpxA/R two component system (TCS) in the invasive abilities of AIEC HM605, a colonic mucosa-associated CD isolate. A mutation in cpxR was shown to be defective in the invasion of epithelial cells and this defect was shown to be independent of motility or the expression of Type 1 fimbriae, factors that have been shown to be involved in the invasion of another strain of AIEC, isolated from a patient with ileal CD, called LF82. The CpxA/R TCS responds to disturbances in the cell envelope and has been implicated in the virulence of a number of Gram negative pathogens. In this study it is shown that the CpxA/R TCS regulates the expression of a potentially novel invasin called SinH. SinH is found in a number of invasive strains of E. coli and Salmonella. Moreover work presented here shows that a critical mechanism underpinning AIEC persistence in macrophages is the repair of DNA bases damaged by macrophage oxidants. Together these findings provide evidence to suggest that AIEC are a diverse group of E. coli and possess diverse molecular mechanisms and virulence factors that contribute to the AIEC phenotype. In addition, AIEC may have gone through different evolutionary histories acquiring various molecular mechanisms ultimately culminating in the AIEC phenotype. The gastrointestinal (GI) tract harbors a diverse microbiota; most are symbiotic or commensal however some bacteria have the potential to cause disease (pathobiont). The work presented here provides evidence to support the model that AIEC are pathobionts. AIEC strains can be carried as commensals in healthy guts however, when the intestinal homeostasis is disrupted, such as in the compromised gut of CD patients, AIEC may behave as opportunistic pathogens and cause and/or contribute to disease by driving intestinal inflammation.

The impact of conifer plantation forestry on the ecology of peatland lakes

Blanket bog lakes are a characteristic feature of blanket bog habitats and harbour many rare and threatened invertebrate species. Despite their potential conservation value, however, very little is known about their physico-chemical or biological characteristics in western Europe, and their reference conditions are still unknown in Ireland. Furthermore, they are under considerable threat in Ireland from a number of sources, particularly afforestation of their catchments by exotic conifers. Plantation forestry can potentially lead to the increased input of substances including hydrogen ions (H+), plants nutrients, dissolved organic carbon (DOC), heavy metals and sediment. The aims of this study were to investigate the effect of conifer plantation forestry on the hydrochemistry and ecology of blanket bog lakes in western Ireland. Lake hydrochemistry, littoral Chydoridae (Cladocera) and littoral macroinvertebrate communities were compared among replicate lakes selected from three distinct catchment land use categories: i) unplanted blanket bog only present in the catchment, ii) mature (closed-canopy) conifer plantation forests only present in the catchment and iii) catchments containing mature conifer plantation forests with recently clearfelled areas. All three catchment land uses were replicated across two geologies: sandstone and granite. Lakes with afforested catchments across both geologies had elevated concentrations of phosphorus (P), nitrogen (N), total dissolved organic carbon (TDOC), aluminium (Al) and iron (Fe), with the highest concentrations of each parameter recorded from lakes with catchment clearfelling. Dissolved oxygen concentrations were also significantly reduced in the afforested lakes, particularly the clearfell lakes. This change in lake hydrochemistry was associated with profound changes in lake invertebrate communities. Within the chydorid communities, the dominance of Alonopsis elongata in the unplanted blanket bog lakes shifted to dominance by the smaller bodied Chydorus sphaericus, along with Alonella nana, Alonella excisa and Alonella exigua, in the plantation forestry-affected lakes, consistent with a shift in lake trophy. Similarly, there was marked changes in the macroinvertebrate communities, especially for the Coleoptera and Heteroptera assemblages which revealed increased taxon richness and abundance in the nutrient-enriched lakes. In terms of conservation status, despite having the greatest species-quality scores (SQS) and species richness, three of the four International Union for the Conservation of Nature (IUCN) red-listed species of Coleoptera and Odonata recorded during the study were absent from lakes subject to catchment clearfelling. The relative strengths of bottom-up (forestry-mediated nutrient enrichment) and top-down (fish) forces in structuring littoral macroinvertebrate communities was investigated in a separate study. Nutrient enrichment was shown to be the dominant force acting on communities, with fish having a lesser influence. These results confirmed that plantation forestry poses the single greatest threat to the conservation status of blanket bog lakes in western Ireland. The findings of this study have major implications for the management of afforested peatlands. Further research is required on blanket bog lakes to prevent any further plantation forestry-mediated habitat deterioration of this rare and protected habitat.

FLT3-driven redox signalling in acute myeloid leukaemia

Acute myeloid leukaemia refers to cancer of the blood and bone marrow characterised by the rapid expansion of immature blasts of the myeloid lineage. The aberrant proliferation of these blasts interferes with normal haematopoiesis, resulting in symptoms such as anaemia, poor coagulation and infections. The molecular mechanisms underpinning acute myeloid leukaemia are multi-faceted and complex, with a range of diverse genetic and cytogenetic abnormalities giving rise to the acute myeloid leukaemia phenotype. Amongst the most common causative factors are mutations of the FLT3 gene, which codes for a growth factor receptor tyrosine kinase required by developing haematopoietic cells. Disruptions to this gene can result in constitutively active FLT3, driving the de-regulated proliferation of undifferentiated precursor blasts. FLT3-targeted drugs provide the opportunity to inhibit this oncogenic receptor, but over time can give rise to resistance within the blast population. The identification of targetable components of the FLT3 signalling pathway may allow for combination therapies to be used to impede the emergence of resistance. However, the intracellular signal transduction pathway of FLT3 is relatively obscure. The objective of this study is to further elucidate this pathway, with particular focus on the redox signalling element which is thought to be involved. Signalling via reactive oxygen species is becoming increasingly recognised as a crucial aspect of physiological and pathological processes within the cell. The first part of this study examined the effects of NADPH oxidase-derived reactive oxygen species on the tyrosine phosphorylation levels of acute myeloid leukaemia cell lines. Using two-dimensional phosphotyrosine immunoblotting, a range of proteins were identified as undergoing tyrosine phosphorylation in response to NADPH oxidase activity. Ezrin, a cytoskeletal regulatory protein and substrate of Src kinase, was selected for further study. The next part of this study established that NADPH oxidase is subject to regulation by FLT3. Both wild type and oncogenic FLT3 signalling were shown to affect the expression of a key NADPH oxidase subunit, p22phox, and FLT3 was also demonstrated to drive intracellular reactive oxygen species production. The NADPH oxidase target protein, Ezrin, undergoes phosphorylation on two tyrosine residues downstream of FLT3 signalling, an effect which was shown to be p22phox-dependent and which was attributed to the redox regulation of Src. The cytoskeletal associations of Ezrin and its established role in metastasis prompted the investigation of the effects of FLT3 and NADPH oxidase activity on the migration of acute myeloid leukaemia cell lines. It was found that inhibition of either FLT3 or NADPH oxidase negatively impacted on the motility of acute myeloid leukaemia cells. The final part of this study focused on the relationship between FLT3 signalling and phosphatase activity. It was determined, using phosphatase expression profiling and real-time PCR, that several phosphatases are subject to regulation at the levels of transcription and post-translational modification downstream of oncogenic FLT3 activity. In summary, this study demonstrates that FLT3 signal transduction utilises a NADPH oxidase-dependent redox element, which affects Src kinase, and modulates leukaemic cell migration through Ezrin. Furthermore, the expression and activity of several phosphatases is tightly linked to FLT3 signalling. This work reveals novel components of the FLT3 signalling cascade and indicates a range of potential therapeutic targets.