Molecular genetic analysis of DNA alterations in Irish colorectal cancer

Colorectal cancer is the most common cause of death due to malignancy in nonsmokers in the western world. In 1995 there were 1,757 cases of colon cancer in Ireland. Most colon cancer is sporadic, however ten percent of cases occur where there is a previous family history of the disease. In an attempt to understand the tumorigenic pathway in Irish colon cancer patients, a number of genes associated with colorectal cancer development were analysed in Irish sporadic and HNPCC colon cancer patients. The hereditary forms of colon cancer include Familial adenomatous polyposis coli (FAP) and Hereditary Non-Polyposis Colon Cancer (HNPCC). Genetic analysis of the gene responsible for FAP, (the APC gene) has been previously performed on Irish families, however the genetic analysis of HNPCC families is limited. In an attempt to determine the mutation spectrum in Irish HNPCC pedigrees, the hMSH2 and hMLHl mismatch repair genes were screened in 18 Irish HNPCC families. Using SSCP analysis followed by DNA sequencing, five mutations were identified, four novel and a previously reported mutation. In families where a mutation was detected, younger asyptomatic members were screened for the presence of the predisposing mutation (where possible). Detection of mutations is particularly important for the identification of at risk individuals as the early diagnosis of cancer can vastly improve the prognosis. The sensitive and efficient detection of multiple different mutations and polymorphisms in DNA is of prime importance for genetic diagnosis and the identification of disease genes. A novel mutation detection technique has recently been developed in our laboratory. In order to assess the efficacy and application of the methodology in the analysis of cancer associated genes, a protocol for the analysis of the K-ras gene was developed and optimised. Matched normal and tumour DNA from twenty sporadic colon cancer patients was analysed for K-ras mutations using the Glycosylase Mediated Polymorphism Detection technique. Five mutations of the K-ras gene were detected using this technology. Sequencing analysis verified the presence of the mutations and SSCP analysis of the same samples did not identify any additional mutations. The GMPD technology proved to be highly sensitive, accurate and efficient in the identification of K-ras gene mutations. In order to investigate the role of the replication error phenomenon in Irish colon cancer, 3 polyA tract repeat loci were analysed. The repeat loci included a 10 bp intragenic repeat of the TGF-β-RII gene. TGF-β-RII is involved in the TGF-β epithelial cell growth pathway and mutation of the gene is thought to play a role in cell proliferation and tumorigenesis. Due to the presence of a repeat sequence within the gene, TGFB-RII defects are associated with tumours that display the replication error phenomenon. Analysis of the TGF-β-RII 10 bp repeat failed to identify mutations in any colon cancer patients. Analysis of the Bat26 and Bat 40 polyA repeat sequences in the sporadic and HNPCC families revealed that instability is associated with HNPCC tumours harbouring mismatch repair defects and with 20 % of sporadic colon cancer tumours. No correlation between K-ras gene mutations and the RER+ phenotype was detected in sporadic colon cancer tumours.

Roots and wings: orthodoxy, tradition, and creativity in Irish folk Catholicism

The present work is an exploration of the beliefs and practices of three lay Catholic devotional communities in and around the city of Cork, Ireland. The research is guided by the theory that folk, or popular, religion is a dynamic process in which individuals and groups utilise the resources of orthodoxy, popular tradition, and personal creativity, to better interpret, articulate, and create religious experiences. Ethnographic fieldwork was the principal method of data collection. Four areas of folk religion are given special attention: the use of religious narrative to represent and reproduce religious experience, the use of material artefacts to create channels for sacred presence and activity, the use of ritual and pilgrimage to establish sacred time and space, and the use of prayer to accomplish all of these goals. These sections are followed by a more holistic analysis of the material, a critical examination of the work, and suggestions for further research.

An Irish apostle: articulating and actualising apostolicity in the early Irish church

This thesis examines the earliest extant Latin Lives of Brigit and Patrick; Cogitosus’s Vita Brigidae and Muirchú’s Vita Patricii as evidence for a seventh-century debate on Irish apostolicity. While often dismissed as mere propaganda, this thesis shows they are highly sophisticated demonstrations of the continuing connection that Kildare and Armagh had to their patron saints and their authority. It examines the importance of this connection for concepts of ecclesiastical organisation, teaching authority and episcopal succession against the backdrop of the seventh-century Easter question in the Insular Church. This will show that apostolicity was considered to be intrinsically linked with orthodoxy and universality. A textual focus brings forth general patristic themes and ideas that Irish hagiographers evoked through specific words and phrases. The thesis contextualises hagiographical material using evidence from Hiberno-Latin and early Insular exegetical commentaries, referring to major patristic exegetes such as Origen, Jerome, Augustine, and Gregory the Great as support. The introduction discusses the importance of apostolic ideology for the seventh-century Irish Church, and outlines a methodology for examining such abstract themes. The first chapter looks at how developments in apostolic ideology led to ideas of apostolic primacy seen in the Insular material. Chapters two, three, and four examine metaphors of food and feeding, the fountain and the stream, and the head and the body, as significant articulations of apostolicity. Chapter five examines how corporeal relics were understood as the visible proof of this continuity and preserved a saint’s authority for their episcopal heirs. Chapter six looks at how Muirchú engaged with Patrick’s connection to the universal Church and his self-professed lack of disciplina to reconcile his apostolicity with seventh-century norms. Chapter seven places the issues considered thus far in a thoroughly Insular context by examining how the earliest English sources present the Irish legacy in Northumbria after the synod of Whitby. Chapter eight looks at how the text of Patrick’s Confessio in the Book of Armagh relates to a wider seventh-century campaign by Armagh to rehabilitate Patrick’s apostolicity. The conclusion briefly summarizes the thesis, and suggests further avenues for researching this topic in the Insular material

Home, family and society: women of the Irish landed class, 1860-1914. A Munster case study

The thesis analyses the roles and experiences of female members of the Irish landed class (wives, sisters and daughters of gentry and aristocratic landlords with estates over 1,000 acres) using primary personal material generated by twelve sample families over an important period of decline for the class, and growing rights for women. Notably, it analyses the experiences of relatively unknown married and unmarried women, something previously untried in Irish historiography. It demonstrates that women’s roles were more significant than has been assumed in the existing literature, and leads to a more rounded understanding of the entire class. Four chapters focus on themes which emerge from the sources used and which deal with their roles both inside and outside the home. These chapters argue that: Married and unmarried women were more closely bound to the priorities of their class than their sex, and prioritised male-centred values of family and estate. Male and female duties on the property overlapped, as marriage relationships were more equal than the legislation of the time would suggest. London was the cultural centre for this class. Due to close familial links with Britain (60% of sample daughters married English men) their self-perception was British or English, as well as Irish. With the self-confidence of their class, these women enjoyed cultural and political activities and movements outside the home (sport, travel, fashion, art, writing, philanthropy, (anti-)suffrage, and politics). Far from being pawns in arranged marriages, women were deeply conscious of their marriage decisions and chose socially, financially and personally compatible husbands; they also looked for sexual satisfaction. Childbirth sometimes caused lasting health problems, but pregnancy did not confine wealthy women to an invalid state. In opposition to the stereotypical distant aristocratic mother, these women breastfed their children, and were involved mothers. However, motherhood was not permitted to impinge on the more pressing role of wife

Study abroad and complexity, accuracy and fluency (CAF) development: a longitudinal investigation of French and Chinese Learners of L2 English

This longitudinal study tracked third-level French (n=10) and Chinese (n=7) learners of English as a second language (L2) during an eight-month study abroad (SA) period at an Irish university. The investigation sought to determine whether there was a significant relationship between length of stay (LoS) abroad and gains in the learners' oral complexity, accuracy and fluency (CAF), what the relationship was between these three language constructs and whether the two learner groups would experience similar paths to development. Additionally, the study also investigated whether specific reported out-of-class contact with the L2 was implicated in oral CAF gains. Oral data were collected at three equidistant time points; at the beginning of SA (T1), midway through the SA sojourn (T2) and at the end (T3), allowing for a comparison of CAF gains arising during one semester abroad to those arising during a subsequent semester. Data were collected using Sociolinguistic Interviews (Labov, 1984) and adapted versions of the Language Contact Profile (Freed et al., 2004). Overall, the results point to LoS abroad as a highly influential variable in gains to be expected in oral CAF during SA. While one semester in the TL country was not enough to foster statistically significant improvement in any of the CAF measures employed, significant improvement was found during the second semester of SA. Significant differences were also revealed between the two learner groups. Finally, significant correlations, some positive, some negative, were found between gains in CAF and specific usage of the L2. All in all, the disaggregation of the group data clearly illustrates, in line with other recent enquiries (e.g. Wright and Cong, 2014) that each individual learner's path to CAF development was unique and highly individualised, thus providing strong evidence for the recent claim that SLA is "an individualized nonlinear endeavor" (Polat and Kim, 2014: 186).

Textual criticism and medieval Irish studies

Many textual scholars will be aware that the title of the present thesis has been composed in a conscious revisionary relation to Tim William Machan’s influential Textual Criticism and Middle English Texts. (Tim William Machan, Textual Criticism and Middle English Texts (Charlottesville, 1994)). The primary subjects of Machan’s study are works written in English between the fourteenth and sixteenth centuries, the latter part of the period conventionally labelled Middle English. In contrast, the works with which I am primarily concerned are those written by scholars of Old and Middle Irish in the nineteenth, twentieth and twenty-first centuries. Where Machan aims to articulate the textual and cultural factors that characterise Middle English works as Middle English, the purposes of this thesis are (a) to identify the underlying ideological and epistemological perspectives which have informed much of the way in which medieval Irish documents and texts are rendered into modern editions, and (b) to begin to place the editorial theory and methodology of medieval Irish studies within the broader context of Biblical, medieval and modern textual criticism. Hence, the title is Textual Criticism and Medieval Irish Studies, rather than Textual Criticism and Medieval Irish Texts

English Channel towed sledge seabed images. Phase 2: Analysis of selected tow images

During the 1970s and 1980s, the late Dr Norman Holme undertook extensive towed sledge surveys in the English Channel and some in the Irish Sea. Only a minority of the resulting images were analysed and reported before his death in 1989 but logbooks, video and film material has been archived in the National Marine Biological Library (NMBL) in Plymouth. A study was therefore commissioned by the Joint Nature Conservation Committee and as a part of the Mapping European Seabed Habitats (MESH) project to identify the value of the material archived and the procedure and cost to undertake further work (Phase 1 of the study reported here: Oakley & Hiscock, 2005). Some image analysis was undertaken as a part of Phase 1. Phase 2 (this report) was to further analyse selected images. Having determined in Phase 1 that only the 35 mm photographic transparencies provided sufficient clarity to identify species and biotopes, the tows selected for analysis were ones where 35mm images had been taken. The tows selected for analysis of images were mainly in the vicinity of Plymouth and especially along the area between Rame Head and the region of the Eddystone. The 35 mm films were viewed under a binocular microscope and the taxa that could be recognised recorded in note form. Twenty-five images were selected for inclusion in the report. Almost all of the images were of level sediment seabed. Where rocks were included, it was usually unplanned and the sled was hauled before being caught or damaged. The main biotopes or biotope complexes identified were: SS.SMU.CSaMu. Circalittoral sandy mud. Extensively present between the shore and the Eddystone Reef complex and at depths of about 48 to 52 m. At one site offshore of Plymouth Sound, the turret shell Turritella communis was abundant. In some areas, this biotope had dense anemones, Mesacmaea mitchelli and (more rarely) Cerianthus lloydii. Queen scallops, Aequipecten opercularis and king scallops, Pecten maximus, were sometimes present in small numbers. Hard substratum species such as hydroids, dead mens fingers Alcyonium digitatum and the cup coral Caryophyllia smithii occurred in a few places, probably attached to shells or stones beneath the surface. South of the spoil ground off Hilsea Point at 57m depth, the sediment was muddier but is still assigned to this biotope complex. It is notable that three small sea pens, most likely Virgularia mirabilis, were seen here. SS.SMx.CMx. Circalittoral mixed sediment. Further offshore but at about the same depth as SS.SMU.CSaMu occurred, coarse gravel with some silt was present. The sediment was characterised must conspicuously by small queen scallops, Aequipecten opercularis. Peculiarly, there were ‘bundles’ of the branching bryozoan Cellaria sp. – a species normally found attached to rock. It could not be seen whether these bundles of Cellaria had been brought-together by terebellid worms but it is notable that Cellaria is recorded in historical surveys. As with many other sediments, there were occasional brittle stars, Ophiocomina nigra and Ophiura ophiura. Where sediments were muddy, the burrowing anemone Mesacmaea mitchelli was common. Where pebbles or cobbles occurred, there were attached species such as Alcyonium digitatum, Caryophyllia smithii and the fleshy bryozoan Alcyonidium diaphanum. Undescribed biotope. Although most likely a part of SS.SMx.CMx, the biotope visually dominated by a terebellid worm believed to be Thelepus cincinnatua, is worth special attention as it may be an undescribed biotope. The biotope occurred about 22 nautical miles south of the latitude of the Eddystone and in depths in excess of 70 m. SS.SCS.CCS.Blan. Branchiostoma lanceolatum in circalittoral coarse sand with shell gravel at about 48m depth and less. This habitat was the ‘classic’ ‘Eddystone Shell Gravel’ which is sampled for Branchiostoma lanceolatum. However, no Branchiostoma lanceolatum could be seen. The gravel was almost entirely bare of epibiota. There were occasional rock outcrops or cobbles which had epibiota including encrusting calcareous algae, the sea fan Eunicella verrucosa, cup corals, Caryophyllia smithii, hydroids and a sea urchin Echinus esculentus. The variety of species visible on the surface is small and therefore identification to biotope not usually possible. Historical records from sampling surveys that used grabs and dredges at the end of the 19th century and early 20th century suggest similar species present then. Illustrations of some of the infaunal communities from work in the 1920’s is included in this report to provide a context to the epifaunal photographs.

English Channel towed sledge seabed images. Phase 1: scoping study and example analysis

During the 1970’s and 1980’s, the late Dr Norman Holme undertook extensive towed sledge surveys in the English Channel and some in the Irish Sea. Only a minority of the resulting images were analysed and reported before his death in 1989 but logbooks, video and film material has been archived in the National Marine Biological Library (NMBL) in Plymouth. A scoping study was therefore commissioned by the Joint Nature Conservation Committee and as a part of the Mapping European Seabed Habitats (MESH) project to identify the value of the material archived and the procedure and cost to undertake further work. The results of the scoping study are: 1. NMBL archives hold 106 videotapes (reel-to-reel Sony HD format) and 59 video cassettes (including 15 from the Irish Sea) in VHS format together with 90 rolls of 35 mm colour transparency film (various lengths up to about 240 frames per film). These are stored in the Archive Room, either in a storage cabinet or in original film canisters. 2. Reel-to-reel material is extensive and had already been selectively copied to VHS cassettes. The cost of transferring it to an accepted ‘long-life’ medium (Betamax) would be approximately £15,000. It was not possible to view the tapes as a suitable machine was not located. The value of the tapes is uncertain but they are likely to become beyond salvation within one to two years. 3. Video cassette material is in good condition and is expected to remain so for several more years at least. Images viewed were generally of poor quality and the speed of tow often makes pictures blurred. No immediate action is required. 4. Colour transparency films are in good condition and the images are very clear. They provide the best source of information for mapping seabed biotopes. They should be scanned to digital format but inexpensive fast copying is problematic as there are no between-frame breaks between images and machines need to centre the image based on between-frame breaks. The minimum cost to scan all of the images commercially is approximately £6,000 and could be as much as £40,000 on some quotations. There is a further cost in coding and databasing each image and, all-in-all it would seem most economic to purchase a ‘continuous film’ scanner and undertake the work in-house. 5. Positional information in ships logs has been matched to films and to video tapes. Decca Chain co-ordinates recorded in the logbooks have been converted to latitude and longitude (degrees, minutes and seconds) and a further routine developed to convert to degrees and decimal degrees required for GIS mapping. However, it is unclear whether corrections to Decca positions were applied at the time the position was noted. Tow tracks have been mapped onto an electronic copy of a Hydrographic Office chart. 6. The positions of start and end of each tow were entered to a spread sheet so that they can be displayed on GIS or on a Hydrographic Office Chart backdrop. The cost of the Hydrographic Office chart backdrop at a scale of 1:75,000 for the whole area was £458 incl. VAT. 7. Viewing all of the video cassettes to note habitats and biological communities, even by an experienced marine biologist, would take at least in the order of 200 hours and is not recommended. English Channel towed sledge seabed images. Phase 1: scoping study and example analysis. 6 8. Once colour transparencies are scanned and indexed, viewing to identify seabed habitats and biological communities would probably take about 100 hours for an experienced marine biologist and is recommended. 9. It is expected that identifying biotopes along approximately 1 km lengths of each tow would be feasible although uncertainties about Decca co-ordinate corrections and exact positions of images most likely gives a ±250 m position error. More work to locate each image accurately and solve the Decca correction question would improve accuracy of image location. 10. Using codings (produced by Holme to identify different seabed types), and some viewing of video and transparency material, 10 biotopes have been identified, although more would be added as a result of full analysis. 11. Using the data available from the Holme archive, it is possible to populate various fields within the Marine Recorder database. The overall ‘survey’ will be ‘English Channel towed video sled survey’. The ‘events’ become the 104 tows. Each tow could be described as four samples, i.e. the start and end of the tow and two areas in the middle to give examples along the length of the tow. These samples would have their own latitude/longitude co-ordinates. The four samples would link to a GIS map. 12. Stills and video clips together with text information could be incorporated into a multimedia presentation, to demonstrate the range of level seabed types found along a part of the northern English Channel. More recent images taken during SCUBA diving of reef habitats in the same area as the towed sledge surveys could be added to the Holme images.