Innovation and evolution: challenges and opportunities for 21st century academic and research libraries

A report from the inaugural CONUL (Consortium of National & University Libraries) conference held in the Radisson Blu Hotel, Athlone, June 3rd & 4th 2015.

Characterization of TRAF6 mediated ubiquitination of presenilins and γ-secretase substrates

Post-translational modification of the γ-secretase protease complexes and their substrates has an important role in controlling receptor-initiated signalling events, which are critically important in the pathogenesis of cancer, inflammatory and Alzheimer’s disease. Our lab has previously characterised an interaction between TRAF6 and presenilin-1, which lead to the identification of interleukin-1 (IL-1) receptor type 1 (IL-1R1) and Toll-like receptor-4 (TLR4) as novel γ-secretase substrates. Subsequently our group showed that TRAF6 promoted ubiquitination and γ-secretase cleavage of IL-1R1. The aim of this project is to study the association between TRAF6 and the presenilins, the critical γ-secretase complex components, and to determine the functional importance of TRAF6-mediated ubiquitination of γ-secretase substrates. Firstly, we show that the full-length presenilins are novel substrates of TRAF6-mediated Lysine-63-linked polyubiquitination. Secondly, we show that co-expression of TRAF6 and the presenilins increases the stability and alters the turnover of the presenilins. Thirdly, we reveal that TRAF6-mediated ubiquitination of presenilin does not affect γ-secretase enzyme activity, but may regulate the full-length presenilin functions such as ER Ca2+ signalling. Previously, we have reported IL-1R1 as a novel substrate of TRAF6-mediated ubiquitination. In this study, we identified five lysine residues in the IL-1R1 intracellular domain targeted by TRAF6-mediated polyubiquitination. Furthermore, mutagenesis of these five lysine residues led to decreased IL-1R1 cell surface expression, precluded the ectodomain shedding and attenuated the responsiveness to IL-1β stimulation, demonstrating the critical role of TRAF6 in IL-1R1 trafficking.

The utility of survey and administrative data to generate information for research and outcomes-based oral health services development

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.

A study of diet and health in the elderly; the gut microbiota as a source of bioactive agents

The global proportion of older persons is increasing rapidly. Diet and the intestinal microbiota independently and jointly contribute to health in the elderly. The habitual dietary patterns and functional microbiota components of elderly subjects were investigated in order to identify specific effector mechanisms. A study of the dietary intake of Irish community-dwelling elderly subjects showed that the consumption of foods high in fat and/or sugar was excessive, while consumption of dairy foods was inadequate. Elderly females typically had a more nutrient- dense diet than males and a considerable proportion of subjects, particularly males, had inadequate intakes of calcium, magnesium, vitamin D, folate, zinc and vitamin C. The association between dietary patterns, glycaemic index and cognitive function was also investigated. Elderly subjects consuming ‘prudent’ dietary patterns had better cognitive function compared to those consuming ‘Western’ dietary patterns. Furthermore, fully-adjusted regression models revealed that a high glycaemic diet was associated with poor cognitive function, demonstrating a new link between nutrition and cognition. An extensive screening study of the elderly faecal-derived microbiota was also undertaken to examine the prevalence of antimicrobial production by intestinal bacteria. A number of previously characterised bacteriocins were isolated (gassericin T, ABP-118, mutacin II, enterocin L-50 and enterocin P) in this study. Interestingly, a Lactobacillus crispatus strain was found to produce a potentially novel antimicrobial compound. Full genome sequencing of this strain revealed the presence of three loci which exhibited varying degrees of homology with the genes responsible for helveticin J production in Lb. helveticus. An additional study comparing the immunomodulatory capacity of ‘viable’ and ‘non-viable’ Bifidobacterium strains found that Bifidobacterium-fermented milks (BFMs) containing ‘non-viable’ cells could stimulate levels of IL-10 and TNF-α in a manner similar to those stimulated by BFMs containing ‘viable’ cells in vitro.

Management of safety climate and the psychosocial work environment – new challenges for occupational health and safety professionals?

Introduction: The work environment and Occupational Health and Safety (OHS) practice have changed over the last number of years. A holistic OHS approach has been recommended by the authorities in this field (e.g. World Health Organisation (WHO), European Agency for Safety and Health at Work (EU-OSHA) and the International Labour Organisation (ILO)). This involves a unified action engaging elements of the physical and psychosocial workplace with greater focus on prevention and promotion of health and wellbeing. The health and safety practitioner (HSP) has been recognised as one of the main agents for implementation of OHS. Within an organisation they act as a leader of change and a professional who shapes health and safety while safeguarding the wellbeing of individuals at work. Additionally, safety climate (SC) has been developed as an essential concept for OHS of an organisation, its productivity and the wellbeing of its workforce. Scholars and practitioners have recognised the great need for further empirical evidence on the HSP’s role in a changing work environment that increasingly requires the use of preventative measures and the assessment and management of psychosocial work-related risks. This doctoral research brings together the different concepts used in OHS and Public Health including SC, Psychosocial workplace risks, Health Promotion and OHS performance. The associations between these concepts are analysed bearing in mind the WHO Healthy Workplace Framework and three of its main components (physical and psychosocial work environment and health resources). This thesis aims to establish a deeper understanding of the practice and management of OHS in Ireland and the UK, exploring the role of HSPs (employed in diverse sectors of activity) and of SC in the OHS of organisations. Methods: One systematic review and three cross-sectional research studies were performed. The systematic review focussed on the evidence compiled for the association of SC with accidents and injuries at work, clarifying this concept’s definition and its most relevant dimensions. The second article (chapter 3) explored the association of SC with accidents and injuries in a sample of workers (n=367) from a pharmaceutical industry and compared permanent with non-permanent workers. Associations of safety climate with employment status and with self-reported occupational accidents/injuries were studied through logistic regression modelling. The third and fourth papers in this thesis investigated the main tasks performed by HSPs, their perceptions of SC, health climate (HC), psychosocial risk factors and health outcomes as well as work efficacy. Validated questionnaires were applied to a sample of HSPs in Ireland and UK, members of the Institute of Occupational Safety and Health (n=1444). Chi-square analysis and logistic regression were used to assess the association between HSPs work characteristics and their involvement in the management of Psychosocial Risk Factors, Safety Culture and Health Promotion (paper 3). Multiple linear regression analysis was used to determine the association between SC, HC, psychosocial risk factors and health outcomes (general health and mental wellbeing) and self-efficacy. Results: As shown in the systematic review, scientific evidence is unable to establish the widely assumed causal link between SC and accidents and injuries. Nevertheless, the current results suggested that, particularly, the organisational dimensions of SC were associated with accidents and injuries and that SC is linked to health, wellbeing and safety performance in the organisation. According to the present research, contingent workers had lower SC perceptions but showed a lower accident/injury rate than their permanent colleagues. The associations of safety climate with accidents/injuries had opposite directions for the two types of workers as for permanent employees it showed an inverse relationship while for temporary workers, although not significant, a positive association was found. This thesis’ findings showed that HSPs are, to a very small degree, included in activities related to psychosocial risk management and assessment, to a moderate degree, involved in HP activities and, to a large degree, engaged in the management of safety culture in organisations. In the final research study, SC and HC were linked to job demands-control-support (JDCS), health, wellbeing and efficacy. JDCS were also associated with all three outcomes under study. Results also showed the contribution of psychosocial risk factors to the association of SC and HC with all the studied outcomes. These associations had rarely been recorded previously. Discussion & Conclusions: Health and safety climate showed a significant association with health, wellbeing and efficacy - a relationship which affects working conditions and the health and wellbeing of the workforce. This demonstrates the link of both SC and HC with the OHS and the general strength or viability of organisations. A division was noticed between the area of “health” and “safety” in the workplace and in the approach to the physical and psychosocial work environment. These findings highlighted the current challenge in ensuring a holistic and multidisciplinary approach for prevention of hazards and for an integrated OHS management. HSPs have shown to be a pivotal agent in the shaping and development of OHS in organisations. However, as observed in this thesis, the role of these professionals is still far from the recommended involvement in the management of psychosocial risk factors and could have a more complete engagement in other areas of OHS such as health promotion. Additionally, a strong culture of health and safety with supportive management and buy-in from all stakeholders is essential to achieve the ideal unified and prevention-focussed approach to OHS as recommended by the WHO, EU-OSHA and ILO.

The cumulative effect of core lifestyle behaviours on the prevalence of hypertension and dyslipidemia

Background: Most cardiovascular disease (CVD) occurs in the presence of traditional risk factors, including hypertension and dyslipidemia, and these in turn are influenced by behavioural factors such as diet and lifestyle. Previous research has identified a group at low risk of CVD based on a cluster of inter-related factors: body mass index (BMI) < 25 Kg/m2, moderate exercise, alcohol intake, non-smoking and a favourable dietary pattern. The objective of this study was to determine whether these factors are associated with a reduced prevalence of hypertension and dyslipidemia in an Irish adult population. Methods: The study was a cross-sectional survey of 1018 men and women sampled from 17 general practices. Participants completed health, lifestyle and food frequency questionnaires and provided fasting blood samples for analysis of glucose and insulin. We defined a low risk group based on the following protective factors: BMI <25 kg/m2; waist-hip ratio (WHR) <0.85 for women and <0.90 for men; never smoking status; participants with medium to high levels of physical activity; light alcohol consumption (3.5–7 units of alcohol/week) and a "prudent" diet. Dietary patterns were assessed by cluster analysis. Results: We found strong significant inverse associations between the number of protective factors and systolic blood pressure, diastolic blood pressure and dyslipidemia. The prevalence odds ratio of hypertension in persons with 1, 2, 3, ≥ 4 protective factors relative to those with none, were 1.0, 0.76, 0.68 and 0.34 (trend p < 0.01). The prevalence odds ratio of dyslipidemia in persons with 1, 2, 3, ≥ 4 protective factors relative to those with none were 0.83, 0.98, 0.49 and 0.24 (trend p = 0.001). Conclusion: Our findings of a strong inverse association between low risk behaviours and two of the traditional risk factors for CVD highlight the importance of 'the causes of the causes' and the potential for behaviour modification in CVD prevention at a population level.

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.

Investigation of growth and stress tolerance characteristics of Cronobacter spp.

Cronobacter spp. are opportunistic pathogens which can be isolated from a wide variety of foods and environments. They are Gram negative, motile, non-spore forming, peritrichous rods of the Enterobacteriaceae family. This food-borne pathogen is associated with the ingestion of contaminated infant milk formula (IMF), causing necrotizing enterocolitis, sepsis and meningitis in neonatal infants. The work presented in this thesis involved the investigation and characterisation of a bank of Cronobacter strains for their ability to tolerate physiologically relevant stress conditions that are commonly encountered in the gastrointestinal tract. While all strains were able to endure the suboptimal conditions tested, noteworthy variations were observed between strains. A collection of these strains were Lux-tagged to determine if their growth could be tracked in IMF by measuring bioluminescence. The resulting strains could be easily and reproducibly monitored in real time by measuring light emission. Following this a transposon mutagenesis library was created in one of the Lux-tagged strains of Cronobacter sakazakii. This library was screened for mutants with affected growth in milk. The majority of mutants identified were associated with amino acid metabolism. The final section of this thesis identified genes involved in the tolerance of C. sakazakii to the milk derived antimicrobial peptide, Lactoferricin B (Lfcin B). This was achieved by creating a transposon mutagenesis library in C. sakazakii and screening for mutants with increased susceptibility to Lfcin B. Overall this thesis demonstrates the variation between Cronobacter strains. It also identifies genes required for growth of the bacteria in milk, as well as genes needed for antimicrobial peptide tolerance.

Issues in the prescribing of psychotropic and psychoactive medication for persons with learning disability: quantitative and qualitative perspectives

The administration of psychotropic and psychoactive medication for persons with learning disability and accompanying mental illness and/or challenging behaviour has undergone much critical review over the past two decades. Assessment and diagnosis of mental illness in this population continues to be psychopharmacological treatment include polypharmacy, irrational prescription procedures and frequent over-prescription. It is clear that all forms of treatment including non-pharmacological interventions need to be driven by accurate and appropriate diagnoses. Where a psychiatric diagnosis has been identified, it greatly aides the selection of appropriate medication, although a specific medication for each diagnosis, as was once hoped, is simply no longer a reality in practice. Part one of the present thesis seeks to address many of the current issues in mental health problems and pharmacological treatment to date. The author undertook a drug prevalence study within both residential and community facilities for persons with learning disability within the Mid-West region of Ireland in order to ascertain the current level of prescribing of psychotropic and psychoactive medications for this population. While many attempts have been made to account for the variation in prescribing, little systematic and empirical research has been undertaken to investigate the factors thought to influence such prescribing. While studies investigating the prescribing behaviours of General Practitioners (GP's) have illustrated the complex nature of the decision making process in the context of general practice, no similar efforts have yet been directed at examining the prescribing behaviours of Consultant Psychiatrists. Using The Critical Incident Technique, the author interviewed Consultant Psychiatrists in the Republic of Ireland to gather information relating not only to their patterns of prescribing for learning disabled populations, but also to examine reasons influencing their prescribing in addition to several related factors. Part two of this thesis presents the findings from this study and a number of issues are raised, not only in relation to attempting to account for the findings from part one of the thesis, but also with respect to implications for improved management and clinical practice.

Synthesis and reactivity of α-diazosulfoxide and α-diazosulfone derivatives

The research described in this thesis involves the synthesis of α-diazo-β-oxo sulfoxides, and exploration of their reactivity. The first chapter includes an introduction to diazocarbonyl chemistry, specifically focusing on the synthesis of diazo compounds, and diazosulfoxide derivatives. The chemistry of sulfines, in particular the generation of α-oxo sulfines and their subsequent trapping as cycloadducts and dimerisation is discussed. The results of this research are discussed in the second and third chapters. The design, synthesis and reactivity of α-diazo-β-oxo sulfoxides is described in chapter 2 where diazo transfer adjacent to sulfoxides to form stable α-diazo-β-oxo sulfoxides has been achieved in cyclic systems. Decomposition of theses α-diazosulfoxides using rhodium carboxylate or carboxamide catalysts is also described. These processes proceed via a Wolff type rearrangement to form α-oxo sulfine intermediates, which were trapped as cycloadducts with dienes. In the absence of a diene trap, dimerisation of the sulfine intermediate was observed. Intramolecular C-H insertion reasctios of α-diazo-α-sulfonyl esters to form substituted sulfolane esters is described in chapter 3. The reactivity of these sulfolane esters is briefly explored. The fourth chapter contains the experimental details and the spectral and analytical data for all new compounds reported.

Chemistry of B1- and B10- boranes containing halogen or pseudohalogen groups

The research described in this thesis involved the chemistry of borane-species which contain one or more halide or pseudohalide groups. Both monoboron species e.g. [BH3X]- and "cluster" borane species e.g. [B10H9X]2- and I-Se B11H10 were studied. The first chapter is a review of the syntheses, properties and reactions of halide and pseudohalide species containing from one to ten boron atoms. Chapter Two is a theoretical investigation of' the electronic and molecular structures of two series of boranes i. e. [BH3X]- and [B10H9X]2- where X = H, CI, CN, NCS, SCN and N3. The calculational method used was the Modified Neglect of Differential Overlap (MNDO) method of Dewar et al. The results were compared where possible with experimental results such as the X-ray crystallographically determined structures of [BH3CI]- and [B10H10]2-. Chapter Three concerns halogenated selenaborane clusters and reports an improved synthesis of 12-Br-SeB11H10 and the first structural data for a simple non-metal containing selenaborane cage with the X-ray crystallographically determined structure of 12-1-SeB11H10. Finally, an indepth n.m.r. study of Se2B9H9 is also reported together with attempts to halogenate this compound. The last two chapters are based on single boron systems. Chapter Four concerns the synthetic routes to amine-boranes and -cyanoboranes from [BH4]- and [BH3CN]- substrates. This chapter discusses some difficulties encountered when polyamines were used in these reactions. The characterisation of an unusual ketone isolated from some of these reactions, the X-ray crystallographically determined structure of 4-dimethylamino-pyridine-cyanoborane and a new route to pyrazabole dimeric species are also discussed. The final chapter reports on work carried out at producing BH2X (X = H, CN) adducts of aminophosphines. Three routes were attempted to generate P-B and N-B bonded species with varying degrees of success. Some unusual products of these reactions are discussed including [Ph2(O) PPPh2 ] [Ph2NH]2, the structure of which was determined by X-ray crystallography.

The psychology of immersion and development of a quantitative measure of immersive response in games

This study sets out to investigate the psychology of immersion and the immersive response of individuals in relation to video and computer games. Initially, an exhaustive review of literature is presented, including research into games, player demographics, personality and identity. Play in traditional psychology is also reviewed, as well as previous research into immersion and attempts to define and measure this construct. An online qualitative study was carried out (N=38), and data was analysed using content analysis. A definition of immersion emerged, as well as a classification of two separate types of immersion, namely, vicarious immersion and visceral immersion. A survey study (N=217) verified the discrete nature of these categories and rejected the null hypothesis that there was no difference between individuals' interpretations of vicarious and visceral immersion. The primary aim of this research was to create a quantitative instrument which measures the immersive response as experienced by the player in a single game session. The IMX Questionnaire was developed using data from the initial qualitative study and quantitative survey. Exploratory Factor Analysis was carried out on data from 300 participants for the IMX Version 1, and Confirmatory Factor Analysis was conducted on data from 380 participants on the IMX Version 2. IMX Version 3 was developed from the results of these analyses. This questionnaire was found to have high internal consistency reliability and validity.

Cereal products for specific dietary requirements. Evaluation and improvement of technological and nutritional properties of gluten free raw materials and end products

Coeliac disease is one of the most common food intolerances worldwide and at present the gluten free diet remains the only suitable treatment. A market overview conducted as part of this thesis on nutritional and sensory quality of commercially available gluten free breads and pasta showed that improvements are necessary. Many products show strong off-flavors, poor mouthfeel and reduced shelf-life. Since the life-long avoidance of the cereal protein gluten means a major change to the diet, it is important to also consider the nutritional value of products intending to replace staple foods such as bread or pasta. This thesis addresses this issue by characterising available gluten free cereal and pseudocereal flours to facilitate a better raw material choice. It was observed that especially quinoa, buckwheat and teff are high in essential nutrients, such as protein, minerals and folate. In addition the potential of functional ingredients such as inulin, β-glucan, HPMC and xanthan to improve loaf quality were evaluated. Results show that these ingredients can increase loaf volume and reduce crumb hardness as well as rate of staling but that the effect diverges strongly depending on the bread formulation used. Furthermore, fresh egg pasta formulations based on teff and oat flour were developed. The resulting products were characterised regarding sensory and textural properties as well as in vitro digestibility. Scanning electron and confocal laser scanning microscopy was used throughout the thesis to visualise structural changes occurring during baking and pasta making

Work experience in transition year: a mixed methods study of subject and career choices

Transition Year (TY) has been a feature of the Irish Education landscape for 39 years. Work experience (WE) has become a key component of TY. WE is defined as a module of between five and fifteen days duration where students engage in a work placement in the broader community. It places a major emphasis on building relationships between schools and their external communities and concomitantly between students and their potential future employers. Yet, the idea that participation in a TY work experience programme could facilitate an increased awareness of potential careers has drawn little attention from the research community. This research examines the influence WE has on the subsequent subjects choices made by students along with the effects of that experience on the students’ identities and emerging vocational identities. Socio-cultural Learning Theory and Occupational Choice Theory frame the overall study. A mixed methods approach to data collection was adopted through the administration of 323 quantitative questionnaires and 32 individual semi-structured interviews in three secondary schools. The analysis of the data was conducted using a grounded theory approach. The findings from the research show that WE makes a significant contribution to the students’ sense of agency in their own lives. It facilitates the otherwise complex process of subject choice, motivates students to work harder in their senior cycle, introduces them to the concepts of active, experience-based and self-directed learning, while boosting their self-confidence and nurturing the emergence of their personal and vocational identities. This research is a gateway to further study in this field. It also has wide reaching implications for students, teachers, school authorities, parents and policy makers regarding teaching and learning in our schools and the value of learning beyond the walls of the classroom.