A Big House Divided: Images of Irish Nationhood in Edna O’Brien’s House of Splendid Isolation

In Edna O’Brien’s House of Splendid Isolation (1994), the house, a microcosm for the nation, along with its marginalized occupants, reflect the borders between North and South, past and present. By critically interrogating the ways in which O’Brien’s dilapidated Big House becomes an uncanny borderland, this essay unpacks the ways in which the Irish nation attempts to define itself by “evicting” those who disrupt the laws of state and gender

Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated at PRSS1-PRSS2 (1×10-12) and x-linked CLDN2 (p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). The PRSS1 variant affects susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07

Strangers at Home: Threshold Identities in Contemporary Irish Women’s Writing

This dissertation examines how contemporary Irish women writers dismantle national conceptions linking Irish women to the hearth and home by offering an alternate version of women’s lived experience, which nationalist ideologies have simplified. I consider how these writers define “home”—the domestic, the familiar, the intimate—as complicated by sexuality, exile, and violence. Using Freud’s theory of the uncanny as a lens, I analyze how these writers question established social relations in order to uncover uneasy relationships to self, home, and homeland. In my project, postcolonial theory and transnational feminisms, coupled with trauma theory, facilitate the contextualization of the uncanny as a response to the hybrid identities, dislocations, and effects of violence on gender roles within the nation. The first two chapters examine Edna O’Brien’s later fiction, which unsettles conceptions of the nation by emphasizing the experiences of marginal figures, thereby questioning who belongs within the nation’s borders. The next two chapters on the fiction of Jennifer Johnston and Mary Beckett reveal how the crossing of the public into the private sphere exposes a paradoxical homespace that is both haven and prison for rich Anglo-Irish Dubliners and working-class Catholics in Belfast. The final chapter on Kate O’Riordan’s novels explores issues of exile, alienation, and trauma through a multi-generational lens, revealing how memories of “home” and fraught parent-child relationships at once hinder and facilitate identity formation. In the epilogue, I briefly discuss how contemporary Irish poetry could address the issues raised by the works of fiction examined in my project

Single-use duodenoscope for ERCP performed by endoscopists with a range of experience in procedures of variable complexity

Background and Aims: Expert endoscopists previously reported ERCP outcomes for the first commercialized single-use duodenoscope. We aimed to document usability of this device by endoscopists with different levels of ERCP experience.  Methods: Fourteen “expert” (>2000 lifetime ERCPs) and 5 “less-expert” endoscopists performed consecutive ERCPs in patients without altered pancreaticobiliary anatomy. Outcomes included ERCP completion for the intended indication, rate of crossover to another endoscope, device performance ratings, and serious adverse events.   Results: Two hundred ERCPs including 81 (40.5%) with high complexity (American Society for Gastrointestinal Endoscopy grades 3-4) were performed. Crossover rate (11.3% vs 2.5%, P =.131), ERCP completion rate (regardless of crossovers) (96.3% vs 97.5%, P =.999), median ERCP completion time (25.0 vs 28.5 minutes, P =.130), mean cannulation attempts (2.8 vs 2.8, P =.954), and median overall satisfaction with the single-use duodenoscope (8.0 vs 8.0 [range, 1.0-10.0], P =.840) were similar for expert versus less-expert endoscopists, respectively. The same metrics were similar by procedural complexity except for shorter median completion time for grades 1 to 2 versus grades 3 to 4 (P <.001). Serious adverse events were reported in 13 patients (6.5%).   Conclusions: In consecutive ERCPs including high complexity procedures, endoscopists with varying ERCP experience had good procedural success and reported high device performance ratings. (Clinical trial registration number: NCT04223830.

Tumor Size Differences Between Preoperative Endoscopic Ultrasound and Postoperative Pathology for Neoadjuvant-Treated Pancreatic Ductal Adenocarcinoma Predict Patient Outcome

BACKGROUND & AIMS: The assessment of therapeutic response after neoadjuvant treatment and pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) has been an ongoing challenge. Several limitations have been encountered when employing current grading systems for residual tumor. Considering endoscopic ultrasound (EUS) represents a sensitive imaging technique for PDAC, differences in tumor size between preoperative EUS and postoperative pathology after neoadjuvant therapy were hypothesized to represent an improved marker of treatment response. METHODS: For 340 treatment-naïve and 365 neoadjuvant-treated PDACs, EUS and pathologic findings were analyzed and correlated with patient overall survival (OS). A separate group of 200 neoadjuvant-treated PDACs served as a validation cohort for further analysis. RESULTS: Among treatment-naïve PDACs, there was a moderate concordance between EUS imaging and postoperative pathology for tumor size (r = 0.726, p\u3c0.001) and AJCC 8(th) edition T-stage (r = 0.586, p\u3c0.001). In the setting of neoadjuvant therapy, a decrease in T-stage correlated with improved 3-year OS rates (50% vs. 31%, p\u3c0.001). Through recursive partitioning, a cutoff of ≥47% tumor size reduction was also found to be associated with improved OS (67% vs. 32%, p\u3c0.001). Improved OS using a ≥47% threshold was validated using a separate cohort of neoadjuvant-treated PDACs (72% vs. 36%, p\u3c0.001). By multivariate analysis, a reduction in tumor size by ≥47% was an independent prognostic factor for improved OS (p=0.007). CONCLUSIONS: The difference in tumor size between preoperative EUS imaging and postoperative pathology among neoadjuvant-treated PDAC patients is an important prognostic indicator and may guide subsequent chemotherapeutic management

Non-functional pancreatic neuroendocrine tumours: ATRX/DAXX and alternative lengthening of telomeres (ALT) are prognostically independent from ARX/PDX1 expression and tumour size

OBJECTIVE: Recent studies have found aristaless-related homeobox gene (ARX)/pancreatic and duodenal homeobox 1 (PDX1), alpha-thalassemia/mental retardation X-linked (ATRX)/death domain-associated protein (DAXX) and alternative lengthening of telomeres (ALT) to be promising prognostic biomarkers for non-functional pancreatic neuroendocrine tumours (NF-PanNETs). However, they have not been comprehensively evaluated, especially among small NF-PanNETs ( 642.0 cm). Moreover, their status in neuroendocrine tumours (NETs) from other sites remains unknown.DESIGN: An international cohort of 1322 NETs was evaluated by immunolabelling for ARX/PDX1 and ATRX/DAXX, and telomere-specific fluorescence in situ hybridisation for ALT. This cohort included 561 primary NF-PanNETs, 107 NF-PanNET metastases and 654 primary, non-pancreatic non-functional NETs and NET metastases. The results were correlated with numerous clinicopathological features including relapse-free survival (RFS).RESULTS: ATRX/DAXX loss and ALT were associated with several adverse prognostic findings and distant metastasis/recurrence (p&lt;0.001). The 5-year RFS rates for patients with ATRX/DAXX-negative and ALT-positive NF-PanNETs were 40% and 42% as compared with 85% and 86% for wild-type NF-PanNETs (p&lt;0.001and p&lt;0.001). Shorter 5-year RFS rates for 642.0cm NF-PanNETs patients were also seen with ATRX/DAXX loss (65% vs 92%, p=0.003) and ALT (60% vs 93%, p&lt;0.001). By multivariate analysis, ATRX/DAXX and ALT status were independent prognostic factors for RFS. Conversely, classifying NF-PanNETs by ARX/PDX1 expression did not independently correlate with RFS. Except for 4% of pulmonary carcinoids, ATRX/DAXX loss and ALT were only identified in primary (25% and 29%) and NF-PanNET metastases (62% and 71%).CONCLUSIONS: ATRX/DAXX and ALT should be considered in the prognostic evaluation of NF-PanNETs including 642.0 cm tumours, and are highly specific for pancreatic origin among NET metastases of unknown primary