Micronutrient intakes and the role of nutritional supplements in the diets of Irish adults and pre-school children

To investigate micronutrient intakes and the role of nutritional supplements in the diets of Irish adults aged 18-64 years and pre-school children aged 1-4 years. Analysis is based on data from the National Adult Nutrition Survey (NANS) (n=1274) and the National Pre-School Nutrition Survey (NPNS) (n=500). Food and beverage intakes and nutritional supplement use were recorded using 4-day food records. Nutrients were estimated using WISP© which is based on McCance and Widdowson’s The Composition of Foods, 6thEd and the Irish Food Composition Database. “Meats”, “milk/yoghurt”, “breads”, “fruit/fruit juices” and “breakfast cereals” made important contributions to the intakes of a number of micronutrients. Micronutrient intakes were generally adequate, with the exception of iron (in adult females and 1 year olds) and vitamin D (in all population groups). For iron, zinc, copper and vitamin B6, up to 2% of adults had intakes that exceeded the upper limit (UL). Small proportions of children had intakes of zinc (11%), copper (2%), retinol (4%) and folic acid (5%) exceeding the UL. Nutritional supplements (predominantly multivitamin and/or mineral preparations) were consumed by 28% of adults and 20% of pre-school children. Among users, supplements were effective in reducing the % with inadequate intakes for vitamins A and D (both population groups) and iron (adult females only). Supplement users had a lower prevalence of inadequate intakes for vitamin A and iron compared to non-users. In adults only, users had a lower prevalence of inadequate intakes for magnesium, calcium and zinc, and displayed better compliance with dietary recommendations and lifestyle characteristics compared with non-users. There is poor compliance among women of childbearing age for the recommendation to take a supplement containing 400µg/day of folic acid. These findings are important for the development of nutrition policies and future recommendations for adults and pre-school children in Ireland and the EU.

Fas ligand expression and tumour immune evasion; the role of prostaglandin E2 and the EP1 receptor

Background and Aim: During carcinogenesis, tumours develop multiple mechanisms to evade the immune system and suppress the anti-tumour immune response. Upregulation of Fas Ligand (FasL/CD95L) expression may represent one such mechanism. FasL is a member of the tumour necrosis factor superfamily that triggers apoptotic cell death following ligation to its receptor Fas. Numerous studies have demonstrated upregulated FasL expression in tumor cells, with FasL expression associated with numerous pro-tumorigenic effects. However, little is known about the mechanisms that regulate FasL expression in tumours. The cyclooxgenase (COX) signalling pathway may play an important role in colon carcinogenesis, via the production of prostaglandins, in particular PGE2. PGE2 signals through four different receptor subtypes, EP1 – EP4. Thus, the aim of this study was to investigate the effect of targeting the PGE2-FasL signaling pathway. Results: (i) PGE2 induces FasL expression via the EP1 receptor in colon cancer cells. (ii) Suppression of FasL expression in colon tumour cells in vivo significantly delays and reduces tumour growth. (iii) Blocking EP1 receptor signaling, or suppression of the EP1 receptor in colon tumour cells, reduces tumour growth in vivo. Suppression of tumour growth correlates in part with suppression of FasL expression. (iv) The reduction in tumour growth is associated with an improved anti-tumour immune response. Tumour infiltration by Treg cells and macrophages was reduced, and the cytotoxic activity of CTL generated from splenocytes isolated from these mice increased. Conclusion: 1) Targeting FasL expression by blocking PGE2-EP1 receptor signalling reduces tumour development in vivo. 2) The mechanism is indirect but is associated with an increased anti-tumour immune response. Thus, unraveling the mechanisms regulating FasL expression and the pro-tumorigenic effects of the EP1 receptor may aid in the search for new therapeutic targets against colon cancer.

The role played by angiotensin (1-7) in the regulation of renal haemodynamics and excretory function in anesthetized rats

Initial studies have demonstrated that intra- renal infusion of Ang (1-7) caused a diuresis and natriuresis that was proportional to the degree of activation of the Renin Angiotensin Aldosterone System (RAAS). This raised the question as why the magnitude of this diuresis and natriuresis was compromised in rats receiving a high sodium diet (suppressed RAAS) and enhanced in low sodium fed rats (activated RAAS)? Could the answer lie with changes in intra-renal AT1 or Mas receptor expression? Interestingly, the observed Ang (1-7) induced increases in sodium and water excretion in rats receiving either a low or normal sodium diet were and blocked in the presence of the AT 1 receptor antagonist (Losartan) in the presence of the, 'Mas' receptor antagonist (A-779). These data suggest that both AT1 and 'Mas' receptors need to be functional in order to fully mediate the renal responses to intra-renal Ang (1-7) infusion. Importantly, further experimentation also revealed that there is a proportional relationship between AT 1 receptor expression in the rat renal cortex and the magnitude of the excretory actions of intra renal Ang (1-7) infusion, which is only partially dependent on the level of 'Mas' receptor expression. These observations suggest that although Ang (1-7) induced increases in sodium and water excretion are mediated by the Mas receptor, the magnitude of these excretory responses appear to be dependent upon the level of AT 1 receptor expression and more specifically Ang II/ AT 1 receptor signalling. Thus in rats receiving a low sodium diet, Ang (1-7) acts via the Mas receptor to inhibit Ang II/ AT 1 receptor signalling. In rats receiving a high sodium diet the down regulated AT 1 receptor expression implies a reduction in Ang II/ AT 1 receptor signalling which renders the counter-regulatory effects of intra-renal Ang (1-7) infusion redundant.

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

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

The role of presenilin 1 and presenilin 2 in IL-1β-, LPS- and TNFα- mediated signalling events

The importance of γ-secretase protease activities in development, neurogenesis and the immune system are highlighted by the diversity of its substrates and phenotypic characterization of Presenilin (PS)-deficient transgenic animals. Since the discovery of Amyloid precursor protein (APP) and it’s cleavage by γ-secretase complexes, over 90 other type I membrane proteins have been identified as γ-secretase substrates. We have identified interleukin-1 (IL-1) receptor type I (IL-1R1), toll-like receptor 4 (TLR4) and tumour necrosis factor-α (TNFα) receptor-1 (TNFR1) as novel substrates for - secretase cleavage, which play an important role in innate immunity. In this study, using PS-deficient cells and PS-knockout animal models we examined the role of PS proteins, PS1 and PS2, in IL-1R1-, TLR4- and TNFR1- mediated inflammatory responses. Data presented show that in response to IL- 1β, lipopolysaccharide (LPS) or TNFα, immortalised fibroblasts from PS2- deficient animals have diminished production of specific cytokines and chemokine, with differential reduction in nuclear factor-κB (NF-κB) and (mitogen activated protein kinase) MAPK activities. In contrast, no defect in the response to IL-1β, LPS or TNFα was observed in PS1-deficient immortalised fibroblasts. These observations were confirmed using bone marrow-derived macrophages from PS2-null mice, which also display impaired responsiveness to IL-1β- and LPS, with decreased production of inflammatory cytokines. Furthermore, in whole animal in vivo responses, we show that PS2-deficient animals display ligand (IL-1β, LPS and TNFα)-dependent alterations in the production of specific pro-inflammatory cytokines or chemokines. Importantly, this reduced responsiveness to IL-1β, LPS or TNFα is independent of γ- secretase protease activity and γ-secretase cleavage of TNFR1, IL-1R1 or TLR4. These observations suggest a novel γ-secretase-independent role of PS2 in the regulation of innate immune responsiveness and challenge current concepts regarding the regulation of IL-1β-, LPS- and TNFα-mediated immune signalling.

Between respectability and disgrace: schismogenesis and the regeneration of inequality, stigma and social exclusion in Limerick

The thesis examines cultural processes underpinning the emergence, institutionalisation and reproduction of class boundaries in Limerick city. The research aims to bring a new understanding to the contemporary context of the city’s urban regeneration programme. Acknowledging and recognising other contemporary studies of division and exclusion, the thesis creates a distinctive approach which focuses on uncovering the cultural roots of inequality, educational disadvantage, stigma and social exclusion and the dynamics of their social reproduction. Using Bateson’s concept of schismogenesis (1953), the thesis looks to the persistent, but fragmented culture of community and develops a heuristic ‘symbolic order of the city’. This is defined as “…a cultural structure, the meaning making aspect of hierarchy, the categorical structures of world understanding, the way Limerick people understand themselves, their local and larger world” (p. 37). This provides a very different departure point for exploring the basis for urban regeneration in Limerick (and everywhere). The central argument is that if we want to understand the present (multiple) crises in Limerick we need to understand the historical, anthropological and recursive processes underpinning ‘generalised patterns of rivalry and conflict’. In addition to exploring the historical roots of status and stigma in Limerick, the thesis explores the mythopoesis of persistent, recurrent narratives and labels that mark the boundaries of the city’s identities. The thesis examines the cultural and social function of ‘slagging’ as a vernacular and highly particularised form of ironic, ritualised and, often, ‘cruel’ medium of communication (often exclusion). This is combined with an etymology of the vocabulary of Limerick slang and its mythological base. By tracing the origins of many normalised patterns of Limerick speech ‘sayings’, which have long since forgotten their roots, the thesis demonstrates how they perform a significant contemporary function in maintaining and reinforcing symbolic mechanisms of inclusion/exclusion. The thesis combines historical and archival data with biographical interviews, ethnographic data married to a deep historical hermeneutic analysis of this political community.

Characterization of the degradation of wild-type and mutant HFE proteins during stress signalling in the endoplasmic reticulum

HFE is a transmembrane protein that becomes N-glycosylated during transport to the cell membrane. It acts to regulate cellular iron uptake by interacting with the Type 1 transferrin receptor and interfering with its ability to bind iron-loaded transferrin. There is also evidence that HFE regulates systemic iron levels by binding to the Type II transferrin receptor although the mechanism by which this occurs is still not well understood. Mutations to HFE that disrupt this function, or physiological conditions that decrease HFE protein levels, are associated with increased iron uptake, and its accumulation in tissues and organs. This is exemplified by the point mutation that results in conversion of cysteine residue 282 to tyrosine (C282Y), and gives rise to the majority of HFE-related hemochromatoses. The C282Y mutation prevents the formation of a disulfide bridge and disrupts the interaction with its co-chaperone β2-microglobulin. The resulting misfolded protein is retained within the endoplasmic reticulum (ER) where it activates the Unfolded Protein Response (UPR) and is subjected to proteasomal degradation. The absence of functional HFE at the cell surface leads to unregulated iron uptake and iron loading. While the E3 ubiquitin ligase involved in the degradation of HFE-C282Y has been identified, the mechanism by which it is targeted for degradation remains relatively obscure. The primary objective of this project was to further our understanding of how the iron regulatory HFE protein is targeted for degradation. Our studies suggest that the glycosylation status, and the active process of deglycosylation, are central to this process. We identified a number of additional factors that can contribute towards degradation and explored their regulation during ER stress conditions.

The use of fault detection and diagnostics to reduce air handling unit energy consumption

The contribution of buildings towards total worldwide energy consumption in developed countries is between 20% and 40%. Heating Ventilation and Air Conditioning (HVAC), and more specifically Air Handling Units (AHUs) energy consumption accounts on average for 40% of a typical medical device manufacturing or pharmaceutical facility’s energy consumption. Studies have indicated that 20 – 30% energy savings are achievable by recommissioning HVAC systems, and more specifically AHU operations, to rectify faulty operation. Automated Fault Detection and Diagnosis (AFDD) is a process concerned with potentially partially or fully automating the commissioning process through the detection of faults. An expert system is a knowledge-based system, which employs Artificial Intelligence (AI) methods to replicate the knowledge of a human subject matter expert, in a particular field, such as engineering, medicine, finance and marketing, to name a few. This thesis details the research and development work undertaken in the development and testing of a new AFDD expert system for AHUs which can be installed in minimal set up time on a large cross section of AHU types in a building management system vendor neutral manner. Both simulated and extensive field testing was undertaken against a widely available and industry known expert set of rules known as the Air Handling Unit Performance Assessment Rules (APAR) (and a later more developed version known as APAR_extended) in order to prove its effectiveness. Specifically, in tests against a dataset of 52 simulated faults, this new AFDD expert system identified all 52 derived issues whereas the APAR ruleset identified just 10. In tests using actual field data from 5 operating AHUs in 4 manufacturing facilities, the newly developed AFDD expert system for AHUs was shown to identify four individual fault case categories that the APAR method did not, as well as showing improvements made in the area of fault diagnosis.

The impact of first pregnancy and delivery on pelvic floor dysfunction

Background: The first childbirth has the greatest impact on a woman’s pelvic floor when major changes occur. The aim of this study was to comprehensively describe pelvic floor dysfunction (PFD) in young nulliparous women, and its correlation with postnatal pathology. Methods: A prospective study was performed at Cork University Maternity Hospital, Ireland. Initially 1484 nulliparous women completed the validated Australian Pelvic Floor Questionnaire at 15 weeks’ gestation and repeatedly at one year postnatally (N=872). In the second phase, at least one year postnatally, 202 participants without subsequent pregnancies attended the clinical follow up which included: pelvic organ prolapse quantification, a 3D-Transperineal ultrasound scan and collagen level assessment. Results: A high pre-pregnancy prevalence of various types of PFD was detected, which in the majority of cases persisted postnatally and included multiple types of PFD. The first birth had a negative impact on severity of pre-pregnancy symptoms in <15% of cases. Apart from prolapse, vaginal delivery, including instrumental delivery did not increase the risk of PFD symptoms, where as Caesarean section was protective for all types of PFD. The first birth had a bigger impact on pre-existing symptoms of overactive bladder compared to stress urinary incontinence. Pelvic organ prolapse is extremely prevalent in young primiparous women, however usually it is low grade and asymptomatic. Congenital factors and high collagen type III levels play an important role in the aetiology of pelvic organs prolapse. Levator ani trauma is present in one in three women after the first pregnancy and delivery. Conclusion: The main damage to the pelvic floor most likely occurs due to an undiagnosed congenital intrinsic weakness of the pelvic floor structures. PFD is highly associated with first childbirth, however it seems that pregnancy and delivery are contributing factors only which unmask the congenital intrinsic weakness of the pelvic floor support.

New phosphorescence based probes and techniques for the analysis of cellular oxygen and respiration

Real time monitoring of oxygenation and respiration is on the cutting edge of bioanalysis, including studies of cell metabolism, bioenergetics, mitochondrial function and drug toxicity. This thesis presents the development and evaluation of new luminescent probes and techniques for intracellular O2 sensing and imaging. A new oxygen consumption rate (OCR) platform based on the commercial microfluidic perfusion channel μ-slides compatible with extra- and intracellular O2 sensitive probes, different cell lines and measurement conditions was developed. The design of semi-closed channels allowed cell treatments, multiplexing with other assays and two-fold higher sensitivity to compare with microtiter plate. We compared three common OCR platforms: hermetically sealed quartz cuvettes for absolute OCRs, partially sealed with mineral oil 96-WPs for relative OCRs, and open 96-WPs for local cell oxygenation. Both 96-WP platforms were calibrated against absolute OCR platform with MEF cell line, phosphorescent O2 probe MitoXpress-Intra and time-resolved fluorescence reader. Found correlations allow tracing of cell respiration over time in a high throughput format with the possibility of cell stimulation and of changing measurement conditions. A new multimodal intracellular O2 probe, based on the phosphorescent reporter dye PtTFPP, fluorescent FRET donor and two-photon antennae PFO and cationic nanoparticles RL-100 was described. This probe, called MM2, possesses high brightness, photo- and chemical stability, low toxicity, efficient cell staining and high-resolution intracellular O2 imaging with 2D and 3D cell cultures in intensity, ratiometric and lifetime-based modalities with luminescence readers and FLIM microscopes. Extended range of O2 sensitive probes was designed and studied in order to optimize their spectral characteristics and intracellular targeting, using different NPs materials, delivery vectors, ratiometric pairs and IR dyes. The presented improvements provide useful tool for high sensitive monitoring and imaging of intracellular O2 in different measurement formats with wide range of physiological applications.

Biased group decision-making and the effect of computer-mediated communication: separating the effects of anonymity, voting and blind picking

The influence of communication technology on group decision-making has been examined in many studies. But the findings are inconsistent. Some studies showed a positive effect on decision quality, other studies have shown that communication technology makes the decision even worse. One possible explanation for these different findings could be the use of different Group Decision Support Systems (GDSS) in these studies, with some GDSS better fitting to the given task than others and with different sets of functions. This paper outlines an approach with an information system solely designed to examine the effect of (1) anonymity, (2) voting and (3) blind picking on decision quality, discussion quality and perceived quality of information.

Northern Ireland, America and the emerging church movement: Exploring the significance of Peter Rollins and the Ikon collective

The Emerging Church Movement (ECM) is a primarily Western religious phenomenon, identifiable by its critical ‘deconstruction’ of ‘modern’ religion. While most prominent in North America, especially the United States, some of the most significant contributors to the ECM ‘conversation’ have been the Belfast-based Ikon Collective and one of its founders, philosopher Peter Rollins. Their rootedness in the unique religious, political and social landscape of Northern Ireland in part explains their position on the ‘margins’ of the ECM, and provides many of the resources for their contributions. Ikon’s development of ‘transformance art’ and its ‘leaderless’ structure raise questions about the institutional viability of the wider ECM. Rollins’ ‘Pyrotheology’ project, grounded in his reading of post-modern philosophy, introduces more radical ideas to the ECM conversation. Northern Ireland’s ‘Troubles’ and ‘marginal’ location provides the ground from which Rollins and Ikon have been able to expose the boundaries of the ECM and raise questions about just how far the ECM may go in its efforts to transform Western Christianity.

The role of transformative thinking and practice in a property entrepreneur's response to the funding crisis since 2008

This portfolio of exploration explores the role of transformative thinking and practice in a property entrepreneur’s response to the financial crisis which swept over Ireland from 2008. The complexity of this challenge and the mental capacity to meet its demands is at the core of the exploration. This inquiry emerged from the challenges the financial crisis presented to my values, beliefs, assumptions, and theories, i.e. the interpretive lens through which I make meaning of my experiences. Given the issue identified, this inquiry is grounded in aspects of theories of constructive developmental psychology, applied developmental science, and philosophy. Integrating and linking these elements to business practice is the applied element of the Portfolio. As the 2008 crisis unfolded I realised I was at the limits of my way of knowing. I came to understand that the underlying structure of a way of knowing is the ‘subject-object relationship’ i.e. what a way of knowing can reflect upon, look at, have perspective on, in other words, make object, as against what is it embedded in, attached to, identified within, or subject to. My goal became enhancing my awareness of how I made meaning and how new insights, which would transform a way of knowing, are created. The focus was on enhancing my practice. This Portfolio is structured into three essays. Essay One reported on my self-reflection and external evaluation out of which emerged my developmental goals. In Essay Two I undertake a reading for change programme in which different meaning making systems were confronted in order to challenge me as a meaning maker. Essay Three reported on my experiment which concerned the question whether it was possible for me as a property entrepreneur, and for others alike, to retain bank finance in the face of the overwhelming objective of the bank to deleverage their balance sheet of property loans. The output of my research can be grouped into General Developmental and Specific Business Implications. Firstly I address those who are interested in a transformational-based response to the challenges of operating in the property sector in Ireland during a crisis. I outline the apparatus of thought that I used to create insight, and thus transform how I thought, these are Awareness, Subject-object separation, Exploring other’s perspectives from the position of incompleteness, Dialectical thinking and Collingwood’s Questioning activity. Secondly I set out my learnings from the crisis and their impact on entrepreneurial behaviour and the business of property development. I identify ten key insights that have emerged from leading a property company through the crisis. Many of these are grounded in common sense, however, in my experience these were, to borrow Shakespeare’s words, “More honor'd in the breach than the observance” in pre Crisis Ireland. Finally I set out a four-step approach for forging a strategy. This requires my peer practitioners to identify (i) what they are subject to, (ii) Assess the Opportunity or challenge in a Systemic Context, (iii) Explore Multiple Perspectives on the opportunity or Challenge with an Orientation to change how you know and (iv) Using the Questioning Activity to create Knowledge. Based on my experience I conclude that transformative thinking and practice is a key enabler for a property entrepreneur, in responding to a major collapse of traditional (bank debt) funding.