A text become provisional: revisiting the capital of the ruins

This essay is a reexamination of Samuel Beckett's The Capital of the Ruins, the untransmitted radio script written for Raidió Éireann (now Raidió Teilifís Éireann) in 1946 following his work with the Irish Red Cross in Saint Lô. The first half of this essay is concerned with the archival and publishing history of the text. This section examines the variants introduced by various editors or publishers and makes a case for a definitive edition of the text based on the edited photocopy of the typescript held in the Beckett International Foundation archive at the University of Reading. The second half of this essay then uses this close attention to the text to reconsider the focus of The Capital of the Ruins and the extent to which the piece is more firmly directed towards socio-political aspects of post-neutrality Ireland than has previously been identified

One-Step Preservation of Phosphoproteins and Tissue Morphology at Room Temperature for Diagnostic and Research Specimens

BACKGROUND: There is an urgent need to measure phosphorylated cell signaling proteins in cancer tissue for the individualization of molecular targeted kinase inhibitor therapy. However, phosphoproteins fluctuate rapidly following tissue procurement. Snap-freezing preserves phosphoproteins, but is unavailable in most clinics and compromises diagnostic morphology. Formalin fixation preserves tissue histomorphology, but penetrates tissue slowly, and is unsuitable for stabilizing phosphoproteins. We originated and evaluated a novel one-step biomarker and histology preservative (BHP) chemistry that stabilizes signaling protein phosphorylation and retains formalin-like tissue histomorphology with equivalent immunohistochemistry in a single paraffin block. RESULTS: Total protein yield extracted from BHP-fixed, routine paraffin-embedded mouse liver was 100% compared to snap-frozen tissue. The abundance of 14 phosphorylated proteins was found to be stable over extended fixation times in BHP fixed paraffin embedded human colon mucosa. Compared to matched snap-frozen tissue, 8 phosphoproteins were equally preserved in mouse liver, while AMPKβ1 Ser108 was slightly elevated after BHP fixation. More than 25 tissues from mouse, cat and human specimens were evaluated for preservation of histomorphology. Selected tissues were evaluated in a multi-site, independent pathology review. Tissue fixed with BHP showed equivalent preservation of cytoplasmic and membrane cytomorphology, with significantly better nuclear chromatin preservation by BHP compared to formalin. Immunohistochemical staining of 13 non-phosphorylated proteins, including estrogen receptor alpha, progesterone receptor, Ki-67 and Her2, was equal to or stronger in BHP compared to formalin. BHP demonstrated significantly improved immunohistochemical detection of phosphorylated proteins ERK Thr202/Tyr204, GSK3-α/β Ser21/Ser9, p38-MAPK Thr180/Tyr182, eIF4G Ser1108 and Acetyl-CoA Carboxylase Ser79. CONCLUSION: In a single paraffin block BHP preserved the phosphorylation state of several signaling proteins at a level comparable to snap-freezing, while maintaining the full diagnostic immunohistochemical and histomorphologic detail of formalin fixation. This new tissue fixative has the potential to greatly facilitate personalized medicine, biobanking, and phospho-proteomic research

Development and Progress of Ireland's Biobank Network: Ethical, Legal, and Social Implications (ELSI), Standardized Documentation, Sample and Data Release, and International Perspective

0info:eu-repo/semantics/publishe

Spontaneous resolution of lung opacities reported as metastases in a patient with a history of leiomyosarcoma

This is a case of a 69-year-old woman who was diagnosed as having metastatic leiomyosarcoma. She presented with multiple lung opacities on plain films and CT scans following resection of a high-grade leiomyosarcoma of the uterus 16 months earlier. The radiological, oncology, gynaecology and respiratory teams diagnosed metastatic cancer on the basis of the clinical presentation and radiological appearance. Surprisingly, despite no treatment, there was gradual resolution of the lung lesions on plain films. A CT scan 18 months later showed full resolution of the lesions. The consultants from the various specialities involved in this case were unable to give a satisfactory explanation as to why these lesions resolved

ATLANTIC-DIP:raised maternal body mass index (BMI) adversely affects maternal and fetal outcomes in glucose-tolerant women according to International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria

Context: Raised maternal body mass index (BMI) in association with hyperglycemia is associated with adverse pregnancy outcome. The contribution of raised BMI as an independent risk factor for adverse pregnancy outcome is of growing concern and increasing prevalence. Objective: The aim of this study was to investigate the effects of raised maternal BMI on pregnancy outcome in glucose-tolerant women using the International Association of Diabetes and Pregnancy Study Groups criteria. Participants and Setting: We studied a cohort of glucose-tolerant, pregnant women (n = 3656) who were attending antenatal obstetric clinics and were recruited to a universal screening program for gestational diabetes under the ATLANTIC-DIP partnership. Design: We conducted a prospective observational study of pregnancy outcome. Maternal outcomes include glucose, delivery mode, pregnancy-induced hypertension, preeclampsia, antepartum hemorrhage, and postpartum hemorrhage. Fetal outcomes included birth weight, congenital malformation, fetal death, neonatal jaundice, hypoglycemia, and respiratory distress. Results: Increasing maternal BMI was associated with adverse pregnancy outcomes: higher cesarean section rates, preeclampsia, pregnancy-induced hypertension, increased birth weight, and congenital malformation. The association of glucose with adverse pregnancy outcome was weak and did not interact with raised BMI. A BMI threshold of 28 kg/m(2) was associated with a significant rise in adverse pregnancy outcome. Conclusions: Raised maternal BMI, within the overweight range, is associated with adverse pregnancy outcomes. These adverse effects of BMI occur independently of maternal glucose. It is apparent that pregnancy unmasks an underlying unhealthy metabolic milieu in obese and overweight women. (J Clin Endocrinol Metab 97: E608-E612, 2012

Bacterium consortium drives compost stability and degradation of organic contaminants in in-vessel composting process of the mechanically separated organic fraction of municipal solid waste (MS-OFMSW)

peer-reviewedCommercial composting of the mechanically separated organic fraction of municipal solid waste (MS-OFMSW) is employed to stabilize municipal organic waste. Its feasibility is linked to process efficacy and compost stability. Threshold values for stability are imposed by regulatory frameworks. Limited reuse options exist for this material often due to the presence of organic pollutants. The optimisation of the composting process is required to reach stability in a viable timeframe. We evaluated the effects on compost stability and the degradation of organic contaminates by using wood shavings as a bulking agent and increasing the turning frequency in a pilot scale process. The use of wood shavings decreased the time required for compost stability while turning frequency had no impact. The addition of wood shavings to the initial feedstock stimulated microbial activity that in turn decreased the time to compost stability and enhanced the degradation of detected PAHs and short-chain phthalates.Enterprise Irelan

Atlantic-dip: raised maternal body mass index (bmi) adversely affects maternal and fetal outcomes in glucose-tolerant women according to international association of diabetes and pregnancy study groups (iadpsg) criteria

Context: Raised maternal body mass index (BMI) in association with hyperglycemia is associated with adverse pregnancy outcome. The contribution of raised BMI as an independent risk factor for adverse pregnancy outcome is of growing concern and increasing prevalence. Objective: The aim of this study was to investigate the effects of raised maternal BMI on pregnancy outcome in glucose-tolerant women using the International Association of Diabetes and Pregnancy Study Groups criteria. Participants and Setting: We studied a cohort of glucose-tolerant, pregnant women (n = 3656) who were attending antenatal obstetric clinics and were recruited to a universal screening program for gestational diabetes under the ATLANTIC-DIP partnership. Design: We conducted a prospective observational study of pregnancy outcome. Maternal outcomes include glucose, delivery mode, pregnancy-induced hypertension, preeclampsia, antepartum hemorrhage, and postpartum hemorrhage. Fetal outcomes included birth weight, congenital malformation, fetal death, neonatal jaundice, hypoglycemia, and respiratory distress. Results: Increasing maternal BMI was associated with adverse pregnancy outcomes: higher cesarean section rates, preeclampsia, pregnancy-induced hypertension, increased birth weight, and congenital malformation. The association of glucose with adverse pregnancy outcome was weak and did not interact with raised BMI. A BMI threshold of 28 kg/m(2) was associated with a significant rise in adverse pregnancy outcome. Conclusions: Raised maternal BMI, within the overweight range, is associated with adverse pregnancy outcomes. These adverse effects of BMI occur independently of maternal glucose. It is apparent that pregnancy unmasks an underlying unhealthy metabolic milieu in obese and overweight women. (J Clin Endocrinol Metab 97: E608-E612, 2012

The human face of biobank networks for translational research

The biobanking literature frequently addresses donor and societal issues surrounding biobanking, but the biobanker's perspective is rarely highlighted. While not comprehensive, this article offers an overview of the human aspects of biobanking from the viewpoint of biobank personnel-from biobank formation, through the process, and in addressing post-biobanking issues. As every biobank and biobank network may differ, such factors may vary. Before biobanking can commence, the purpose of the biobank network must be defined, and buy-in achieved from many stakeholders. An attitude of trust and sharing is essential, as is good communication. Developing a biobank is time consuming and laborious. Forming a network requires significantly more time due to the need for cross-institutional harmonization of policies, procedures, information technology considerations, and ethics. Circumstances may dictate whether development occurs top-down and/or bottom-up, as well as whether network management may be independent or by personnel from participating biobanks. Funding tends to be a prominent issue for biobanks and networks alike. In particular, networks function optimally with some level of government support, particularly for personnel. Quality biospecimen collection involves meticulously documented coordination with a network of medical and nursing staff. Examining and sampling operative specimens requires timely collaboration between the surgical and pathology teams. "Catch rates" for samples may be difficult to predict and may occur at a frequency less than anticipated due to factors related to the institution, staff, or specimen. These factors may affect specimen quality, and have a downstream effect on competition for specimens for research. Thus, release of samples requires a fair, carefully constructed sample access policy, usually incorporating an incentive for researchers, and an encouragement to form collaborations. Finally, the public and patient groups should aim to understand the benefits of a biobank network, so that patient care is improved through coordinated biobanking activity.</p

Wnt6 regulates epithelial cell differentiation and is dysregulated in renal fibrosis

Diabetic nephropathy is the most common microvascular complication of diabetes mellitus, manifesting as mesangial expansion, glomerular basement membrane thickening, glomerular sclerosis, and progressive tubulointerstitial fibrosis leading to end-stage renal disease. Here we describe the functional characterization of Wnt6, whose expression is progressively lost in diabetic nephropathy and animal models of acute tubular injury and renal fibrosis. We have shown prominent Wnt6 and frizzled 7 (FzD7) expression in the mesonephros of the developing mouse kidney, suggesting a role for Wnt6 in epithelialization. Importantly, TCF/Lef reporter activity is also prominent in the mesonephros. Analysis of Wnt family members in human renal biopsies identified differential expression of Wnt6, correlating with severity of the disease. In animal models of tubular injury and fibrosis, loss of Wnt6 was evident. Wnt6 signals through the canonical pathway in renal epithelial cells as evidenced by increased phosphorylation of GSK3β (Ser9), nuclear accumulation of β-catenin and increased TCF/Lef transcriptional activity. FzD7 was identified as a putative receptor of Wnt6. In vitro Wnt6 expression leads to de novo tubulogenesis in renal epithelial cells grown in three-dimensional culture. Importantly, Wnt6 rescued epithelial cell dedifferentiation in response to transforming growth factor-β (TGF-β); Wnt6 reversed TGF-β-mediated increases in vimentin and loss of epithelial phenotype. Wnt6 inhibited TGF-β-mediated p65-NF-κB nuclear translocation, highlighting cross talk between the two pathways. The critical role of NF-κB in the regulation of vimentin expression was confirmed in both p65−/−and IKKα/β−/−embryonic fibroblasts. We propose that Wnt6 is involved in epithelialization and loss of Wnt6 expression contributes to the pathogenesis of renal fibrosis.</jats:p