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Item Caries and developmental defect of enamel prevalence in adults with cystic fibrosis(University College Cork, 2024) O'Leary, Fiona; Hayes, Martina; Burke, Francis M.; Roberts, Anthony; Health Research Board; Cystic Fibrosis IrelandObjectives This research had five objectives. 1. To evaluate the available literature regarding oral disease in people with cystic fibrosis specifically caries and developmental defects of enamel. 2. To ascertain the current practices and attitudes of dental practitioners regarding the provision of oral care for people with cystic fibrosis. 3. To ascertain the current practices and attitudes of dental practitioners regarding the provision of dental treatment pre and post solid organ transplantation. 4. To assess a cohort of people with cystic fibrosis for the presence of developmental defects of enamel and compare the results with a control group of people without cystic fibrosis. 5. To measure caries experience in a cohort of people with cystic fibrosis and compare the results with a control group of people without cystic fibrosis. Methods Objective 1 A systematic review of the available literature was conducted for caries experience in people with cystic fibrosis. A second systematic review was conducted assessing the prevalence of developmental defects of enamel in people with cystic fibrosis. Objective 2 & 3 A questionnaire was developed following PPI (patient and public involvement) with representatives of the dental profession and patient advocates from Cystic Fibrosis Ireland. The questionnaire consisted of 56 questions and multiple-choice questions related to cystic fibrosis manifestations and management, dental health certification for solid organ transplantation, and the dental management of people with cystic fibrosis and recipients of solid organ transplants. Dentists were invited to complete the anonymised survey online. Data was collected from 135 dental practitioners. Data was qualitatively analysed. Objective 4 & 5 A total of 92 people with cystic fibrosis and 92 people without cystic fibrosis were recruited for this cross-sectional study. Each participant completed the World Health Organisation's ‘Oral Health Questionnaire for Adults’. Individuals with cystic fibrosis in the study group completed additional questions specifically related to cystic fibrosis diagnosis, treatment and management. All participants underwent an oral examination, performed by two calibrated examiners to assess for the presence of developmental defects of enamel (DDE index), to measure caries experience (DMF) and other clinical variables (periodontal assessment using the CPI-modified index, and oral hygiene status using the Greene–Vermillion index). Collected data was statistically analysed with help from statisticians from the Cystic Fibrosis Registry of Ireland. Results Objectives 1 Studies included in the systematic review demonstrated a trend that caries levels in paediatric populations with cystic fibrosis are lower when compared to a population without cystic fibrosis. Caries levels are higher in adults with cystic fibrosis when compared to populations without cystic fibrosis. Similarly, the majority of included studies indicate that people with cystic fibrosis have a higher prevalence of developmental defects of enamel. Objective 2 & 3 Twenty-four percent (n=32) of dental practitioners were currently providing care for people with cystic fibrosis, 13% (n = 17) did not know, and 63% (n = 85) were not currently providing care for this population. 72% (n = 97) of respondents reported that they were comfortable treating people with cystic fibrosis, 28% (n = 38) said that they were not comfortable treating these patients. Thirty four percent of respondents currently or had previously provided care for recipients of solid organ transplants. 29% (n=36) of dentists had provided dental health certification for individuals undergoing transplantation, only 11% (n=4) had received correspondence or guidance from the patient’s medical team. 88% of respondents consider the currently available literature providing guidance for the provision of dental health certification inadequate. Objective 4 & 5 Sixty-four percent (n=59) of people with cystic fibrosis had developmental defects of enamel, compared to 30% (n=28) of people without cystic fibrosis. The median number of teeth affected by enamel defects in the study group was 1.5, compared to 0 in the control group. The percentage of people with cystic fibrosis with untreated dental caries present was 38% (n=35) compared to 13% (n=12) of people in the control group. The mean DMFT values were higher in the study group compared to the control group but only the decayed value (DT) was statistically significantly higher (0.99 vs. 0.18; (p= <0.001)). Conclusions Objective 1 While there is not a unanimous agreement across all studies, there is a consistent pattern that the prevalence of enamel defects is higher in people with cystic fibrosis compared to individuals without cystic fibrosis. While a pattern emerged that children with cystic fibrosis had lower levels of dental caries compared to healthy children, adults with cystic fibrosis had higher levels of caries compared to adults without cystic fibrosis. Objective 2 & 3 The results from the survey indicate a wide variety in the knowledge, attitudes and practices of dental practitioners regarding the oral health of people with cystic fibrosis. Similarly, the data indicates a wide variation in the provision of treatment for patients undergoing or in receipt of a solid organ transplant. There are currently no guidelines for the provision of dental treatment for people with cystic fibrosis or people pre/post solid organ transplantation. Future research should focus on the development of such guidelines to aid dental practitioners and ensure that patients receive an appropriate standard of care. Objective 4 & 5 In this study the cohort of adults with cystic fibrosis had a higher DMFT when compared to a control population without cystic fibrosis. Adults with cystic fibrosis had a statistically higher prevalence of developmental defects of enamel compared to the control group.Item Bi-directional tumour-host interaction in a murine model(University College Cork, 2001) O'Brien, Mike; Shanahan, FergusTumours evoke immunologic responses yet they continue to grow and develop. The majority of people who develop tumours are immunocompetant, evoke immune responses and yet metastases occur in lymphnodes, potentially the most hostile immune environment. This is the paradox that we are attempting to unravel. It is hoped that this work would eventually lead to improved immunotherapeutic strategies. The primary objective of the work was to study the mechanisms by which tumours of differing origins and antigenic spectra circumvent the anti-tumour immune response to grow and develop. Responses were characterised for two histologically distinct murine tumours grown in immunocompetant, syngeneic mice. Immunological response profiles were defined in terms of lymphocyte proliferation, cytotoxic function and lymphocyte subsets in naive non-tumour bearing mice and mice with increasing tumour burden. The effect of this antitumour immune response on the developing tumour was examined in a model of mixed tumour antigenicity established in our laboratory. The influence of tumour derived immunosuppressive factors on the immune response was examined. These factors were partially characterised and compared to determine if the differing response profiles could be attributed to differing immunosuppressive factors. The possible effect of tumour antigens shed into and processed by the gut associated lymphoid tissue with consequent down regulation of the systemic immune response (Oral Tolerance) to a developing tumour was examined.Item Improved modelling of pumped hydro energy storage(University College Cork, 2012) Deane, John Paul; O'Gallachoir, Brian; McKeogh, Eamon; Eirgrid Plc.Rising greenhouse gas emissions, diminishing fossil fuel reserves and concerns over energy security have led to renewable energy targets that have spurred the growth of variable renewable generation sources such as wind and wave in many countries. The introduction of variable sources of electrical generation makes the operation and modelling of the power system more challenging. Pumped hydro energy storage is a flexible, fast acting generating source with the ability to store large amounts of electricity, and to facilitate the technical integration of variable renewable sources of generation. Recently, there has been resurgence in pumped hydro energy storage as many European countries strive for greater integration of renewables; however, the software tools and techniques used to traditionally model the power system need to be improved in order to capture the operation and role of flexible enabling technologies such as pumped hydro storage. Traditionally deterministic models that simulate the power system at hourly resolution are employed to assess the role and usefulness of pumped hydro storage. In this thesis, techniques are developed and presented to improve the current representation of pumped hydro energy storage, eliminating the weakness of perfect foresight assumption in model simulations. It is also demonstrated that higher temporal resolution simulations of the power system have the ability to capture important aspects of power system operation such as binding ramp rates. New techniques are also put forward for the improved modelling of large pumped storage in the context of wind forecast uncertainty, and it is shown that energy system models can benefit in the modelling of pumped hydro storage by soft-linking with power system models. Overall, this works shows that existing pumped hydro energy storage will play an ever more important role in Ireland as levels of installed wind capacity increase.Item An briathar mí-rialta i nGaeluinn na nDéise(University College Cork, 2004) Uí Fhoghlú, Áine; Ua Suilleabhain, SeanTá an saothar taighde seo bunaithe ar thuairim is triocha uair an chloig dʼabhar a dheineas a thaifeadadh ar fístéip idir 1990-ʼ94 i measc na gcainteoirí is fearr a bhí i nGaeltacht na Rinne agus an tSeana-Phobail ag an am. Ina measc so tá éinne dhéag gur sár-chainteoirí láidre ná tabharfaí tionchar an Bhéarla ná tionchar ghramadach na scoile fé ndeara ar a gcuid Gaeilge. Tá triúr ina measc gur sár-chainteoirí iad a tógadh le Gaeilge sa Rinn agus a bhí ina múinteoirí i rith a saoil. Cainteoirí iad so a bhfuil a gcuid urlabhra ana-shoiléir agus aird acu ar chruinneas gramadaí, aird ná fuil le fáilt ina measc súd a bhí gan oideachas foirmeálta. Tá cúigear sa chnuasach a tógadh le Gaeilge ach a raibh go leor Béarla le clos acu ina n-óige agus bhí cúpla duine acu san as taithí a bheith ag caint na Gaeilge le tamall roimh an taifeadadh. Ar an abhar a dheineas a thaifeadadh bhí mórchuid seanchais, scéalaíochta, amhránaíochta agus stair áitiúil. Nuair a thug Roinn na Nua-Ghaeilge cead agus cuireadh dom an taighde seo a dhéanamh beartaíodh gur saothar deilbhíochta ar Ghaeluinn na nDéise a bheadh ann agus an taighde dírithe ar an mbriathar mí-rialta mar ná raibh a leithéid de shaothar ann roimhe seo sa chanúint sin. Mar sin is é teideal an tsaothair ʻAn briathar mí-rialta i nGaeluinn na nDéiseʼ. Ar dtúis chaitheas éisteacht go grinn leis na téipeanna agus gach sampla de gach briathar mí-rialta a dʼúsáid na cainteoirí a bhreacadh síos, ansan ord agus eagar a chur orthu. De réir mar a bhí an obair ag dul chun cinn bhí eolas nua á nochtadh dom. Cé gurb iad na téipeanna atá mar bhun-fhoinse taighde agam úsáidim leabhair thaighde ar Ghaeluinn na nDéise mar fhoinsí tagartha agus táid seo ar fad liostáilte sa saothar. Is é an Dr. Seán Ua Súilleabháin a stiúraigh an obair.Item Studies in palladium and rhodium catalysis: synthetic strategies for C–C bond formation(University College Cork, 2024) Power, Mark; Mcglacken, Gerard P.; Irish Research Council; Higher Education AuthorityThis thesis concerns studies in palladium and rhodium catalysis for carbon-carbon bond formation. Chapter 1 involves the synergistic use of tetrabutylammonium acetate (NBu4OAc) with palladium catalysis to expand on the synthesis of dibenzofurans via C-H activation. Dibenzofuran and its derivatives are ubiquitous and important medicinal and natural products. Many contain electron-rich aryl rings. Previously, we found that the wellestablished conditions, which promote C−H functionalisation through Concerted MetalationDeprotonation (CMD), proved unsatisfactory for electron-rich diarylether precursors. Herein, we report a Pd-catalysed C−H functionalisation protocol that works with electron-rich arenes. We suspect that tetrabutylammonium acetate can act as base, ligand and solvent, rendering this protocol a simple and efficient route to electron-rich dibenzofurans. A variety of functionalised dibenzofurans are successfully accessed through this protocol. The methodology can be applied to benzochromenes, with varying degrees of success. However, this protocol can be expanded to enable a robust, one-pot Buchwald-Hartwig, C–H activation sequence to access biologically relevant indoloquinoline scaffolds from simple building blocks. In Chapter 2, rhodium-catalysed asymmetric conjugate additions are performed with indolyl boronic acids. The indole ring system represents one of the most abundant and important heterocycles in natural products, Active Pharmaceutical Ingredients (APIs), drugs and other materials. The prominence of indole compounds makes efficient protocols to derivatise the heterocycle highly desirable. A particular importance is placed on asymmetric protocols and utilising unprotected (NH) variants. Herein, we report a Hayashi-Miyaura-type Rh-catalysed asymmetric conjugate addition using free NH indole boronic acids and enones. Each position on the carbocyclic backbone of indole can be accessed, with a variety of enones. Yield of up to 94%, and e.r. values up to 99:1 can be achieved using mild reaction conditions. Furthermore, a 1,2-addition to benzil can be performed in excellent yield and e.r. Finally, a one-pot conjugate addition and intramolecular cyclisation of 7-indolyl boronic acid allows for the synthesis of a novel tetracyclic indole, similar to that found in natural products.