A diagnostic marker for superficial urothelial bladder carcinoma : lack of nuclear ATBF1 (ZFHX3) by immunohistochemistry suggests malignant progression

Background: Pathological stage and grade have limited ability to predict the outcomes of superficial urothelial bladder carcinoma at initial transurethral resection (TUR). AT-motif binding factor 1 (ATBF1) is a tumor suppressive transcription factor that is normally localized to the nucleus but has been detected in the cytoplasm in several cancers. Here, we examined the diagnostic value of the intracellular localization of ATBF1 as a marker for the identification of high risk urothelial bladder carcinoma. Methods: Seven anti-ATBF1 antibodies were generated to cover the entire ATBF1 sequence. Four human influenza hemagglutinin-derived amino acid sequence-tagged expression vectors with truncated ATBF1 cDNA were constructed to map the functional domains of nuclear localization signals (NLSs) with the consensus sequence KR[X10-12]K. A total of 117 samples from initial TUR of human bladder carcinomas were analyzed. None of the patients had received chemotherapy or radiotherapy before pathological evaluation. Results: ATBF1 nuclear localization was regulated synergistically by three NLSs on ATBF1. The cytoplasmic fragments of ATBF1 lacked NLSs. Patients were divided into two groups according to positive nuclear staining of ATBF1, and significant differences in overall survival (P = 0.021) and intravesical recurrence-free survival (P = 0.013) were detected between ATBF1+ (n= 110) and ATBF1− (n=7) cases. Multivariate analysis revealed that ATBF1 staining was an independent prognostic factor for intravesical recurrence-free survival after adjusting for cellular grading and pathological staging (P = 0.008). Conclusions: Cleavage of ATBF1 leads to the cytoplasmic localization of ATBF1 fragments and downregulates nuclear ATBF1. Alterations in the subcellular localization of ATBF1 due to fragmentation of the protein are related to the malignant character of urothelial carcinoma. Pathological evaluation using anti-ATBF1 antibodies enabled the identification of highly malignant cases that had been overlooked at initial TUR. Nuclear localization of ATBF1 indicates better prognosis of urothelial carcinoma

Researching peers and disaster vulnerable communities: an insider perspective

Conducting research among peers and communities that a researcher also serves may be both daunting and rewarding. Researching peers may make the researcher feel uncomfortable raising certain questions that are sensitive or that could be construed to be testing their competencies. This paper is inclined more towards showing that it is advantageous to be an insider, whose position can facilitate collection of information that could not have been accessed, or revealed to an outsider. The paper reports on fieldwork conducted in a low-income country in Sub-Sahara Africa as part of a doctoral study with communities affected by disasters and those that work with such communities. The paper demonstrates the complexities of conducting such research and provides some insights that may be useful to insiders, outsiders or “in-betweeners” embarking on fieldwork in low-income countries and among vulnerable population struggling with manifold stresses and shocks

The relationship between eruptive activity, flank collapse, and sea level at volcanic islands: A long-term (>1 Ma) record offshore Montserrat, Lesser Antilles

Hole U1395B, drilled southeast of Montserrat during Integrated Ocean Drilling Program Expedition 340, provides a long (>1 Ma) and detailed record of eruptive and mass-wasting events (>130 discrete events). This record can be used to explore the temporal evolution in volcanic activity and landslides at an arc volcano. Analysis of tephra fall and volcaniclastic turbidite deposits in the drill cores reveals three heightened periods of volcanic activity on the island of Montserrat (?930 ka to ?900 ka, ?810 ka to ?760 ka, and ?190 ka to ?120 ka) that coincide with periods of increased volcano instability and mass-wasting. The youngest of these periods marks the peak in activity at the Soufrière Hills volcano. The largest flank collapse of this volcano (?130 ka) occurred towards the end of this period, and two younger landslides also occurred during a period of relatively elevated volcanism. These three landslides represent the only large (>0.3 km3) flank collapses of the Soufrière Hills edifice, and their timing also coincides with periods of rapid sea-level rise (>5 m/ka). Available age data from other island arc volcanoes suggests a general correlation between the timing of large landslides and periods of rapid sea-level rise, but this is not observed for volcanoes in intra-plate ocean settings. We thus infer that rapid sea-level rise may modulate the timing of collapse at island arc volcanoes, but not in larger ocean-island settings

Heat flow in the Lesser Antilles island arc and adjacent back arc Grenada basin

Using temperature gradients measured in 10 holes at 6 sites, we generate the first high fidelity heat flow measurements from Integrated Ocean Drilling Program drill holes across the northern and central Lesser Antilles arc and back arc Grenada basin. The implied heat flow, after correcting for bathymetry and sedimentation effects, ranges from about 0.1 W/m² on the crest of the arc, midway between the volcanic islands of Montserrat and Guadeloupe, to 15 km from the crest in the back arc direction. Combined with previous measurements, we find that the magnitude and spatial pattern of heat flow are similar to those at continental arcs. The heat flow in the Grenada basin to the west of the active arc is 0.06 W/m², a factor of 2 lower than that found in the previous and most recent study. There is no thermal evidence for significant shallow fluid advection at any of these sites. Present-day volcanism is confined to the region with the highest heat flow.American Geophysical Union – Geochemistry, Geophysics, Geosystems. This is the publisher’s final pdf. The published article is copyrighted by the American Geophysical Union and can be found at: http://www.agu.org/journals/gc/.Keywords: volcanic arc., Lesser Antilles, IODP, heat flow, back arc, Grenada basinKeywords: volcanic arc., Lesser Antilles, IODP, heat flow, back arc, Grenada basi

Permeability and pressure measurements in Lesser Antilles submarine slides: Evidence for pressure-driven slow-slip failure

Recent studies hypothesize that some submarine slides fail via pressure-driven slow-slip deformation. To test this hypothesis, this study derives pore pressures in failed and adjacent unfailed deep marine sediments by integrating rock physics models, physical property measurements on recovered sediment core, and wireline logs. Two drill sites (U1394 and U1399) drilled through interpreted slide debris; a third (U1395) drilled into normal marine sediment. Near-hydrostatic fluid pressure exists in sediments at site U1395. In contrast, results at both sites U1394 and U1399 indicate elevated pore fluid pressures in some sediment. We suggest that high pore pressure at the base of a submarine slide deposit at site U1394 results from slide shearing. High pore pressure exists throughout much of site U1399, and Mohr circle analysis suggests that only slight changes in the stress regime will trigger motion. Consolidation tests and permeability measurements indicate moderately low (~10⁻¹⁶–10⁻¹⁷ m²) permeability and overconsolidation in fine-grained slide debris, implying that these sediments act as seals. Three mechanisms, in isolation or in combination, may produce the observed elevated pore fluid pressures at site U1399: (1) rapid sedimentation, (2) lateral fluid flow, and (3) shearing that causes sediments to contract, increasing pore pressure. Our preferred hypothesis is this third mechanism because it explains both elevated fluid pressure and sediment overconsolidation without requiring high sedimentation rates. Our combined analysis of subsurface pore pressures, drilling data, and regional seismic images indicates that slope failure offshore Martinique is perhaps an ongoing, creep-like process where small stress changes trigger motion

Late Pleistocene stratigraphy of IODP Site U1396 and compiled chronology offshore of south and south west Montserrat, Lesser Antilles

Marine sediments around volcanic islands contain an archive of volcaniclastic deposits, which can be used to reconstruct the volcanic history of an area. Such records hold many advantages over often incomplete terrestrial data sets. This includes the potential for precise and continuous dating of intervening sediment packages, which allow a correlatable and temporally constrained stratigraphic framework to be constructed across multiple marine sediment cores. Here we discuss a marine record of eruptive and mass-wasting events spanning ~250 ka offshore of Montserrat, using new data from IODP Expedition 340, as well as previously collected cores. By using a combination of high-resolution oxygen isotope stratigraphy, AMS radiocarbon dating, biostratigraphy of foraminifera and calcareous nannofossils, and clast componentry, we identify five major events at Soufriere Hills volcano since 250 ka. Lateral correlations of these events across sediment cores collected offshore of the south and south west of Montserrat have improved our understanding of the timing, extent and associations between events in this area. Correlations reveal that powerful and potentially erosive density-currents traveled at least 33 km offshore and demonstrate that marine deposits, produced by eruption-fed and mass-wasting events on volcanic islands, are heterogeneous in their spatial distribution. Thus, multiple drilling/coring sites are needed to reconstruct the full chronostratigraphy of volcanic islands. This multidisciplinary study will be vital to interpreting the chaotic records of submarine landslides at other sites drilled during Expedition 340 and provides a framework that can be applied to the stratigraphic analysis of sediments surrounding other volcanic islands.Keywords: Debris avalanche, Pyroclastic flows, Late quaternary, Submarine evidenc

Late Pleistocene stratigraphy of IODP Site U1396 and compiled chronology offshore of south and south west Montserrat, Lesser Antilles

Marine sediments around volcanic islands contain an archive of volcaniclastic deposits, which can be used to reconstruct the volcanic history of an area. Such records hold many advantages over often incomplete terrestrial data sets. This includes the potential for precise and continuous dating of intervening sediment packages, which allow a correlatable and temporally constrained stratigraphic framework to be constructed across multiple marine sediment cores. Here we discuss a marine record of eruptive and mass-wasting events spanning ?250 ka offshore of Montserrat, using new data from IODP Expedition 340, as well as previously collected cores. By using a combination of high-resolution oxygen isotope stratigraphy, AMS radiocarbon dating, biostratigraphy of foraminifera and calcareous nannofossils, and clast componentry, we identify five major events at Soufriere Hills volcano since 250 ka. Lateral correlations of these events across sediment cores collected offshore of the south and south west of Montserrat have improved our understanding of the timing, extent and associations between events in this area. Correlations reveal that powerful and potentially erosive density-currents traveled at least 33 km offshore and demonstrate that marine deposits, produced by eruption-fed and mass-wasting events on volcanic islands, are heterogeneous in their spatial distribution. Thus, multiple drilling/coring sites are needed to reconstruct the full chronostratigraphy of volcanic islands. This multidisciplinary study will be vital to interpreting the chaotic records of submarine landslides at other sites drilled during Expedition 340 and provides a framework that can be applied to the stratigraphic analysis of sediments surrounding other volcanic islands

A diagnostic marker for superficial urothelial bladder carcinoma : lack of nuclear ATBF1 (ZFHX3) by immunohistochemistry suggests malignant progression

Background: Pathological stage and grade have limited ability to predict the outcomes of superficial urothelial bladder carcinoma at initial transurethral resection (TUR). AT-motif binding factor 1 (ATBF1) is a tumor suppressive transcription factor that is normally localized to the nucleus but has been detected in the cytoplasm in several cancers. Here, we examined the diagnostic value of the intracellular localization of ATBF1 as a marker for the identification of high risk urothelial bladder carcinoma. Methods: Seven anti-ATBF1 antibodies were generated to cover the entire ATBF1 sequence. Four human influenza hemagglutinin-derived amino acid sequence-tagged expression vectors with truncated ATBF1 cDNA were constructed to map the functional domains of nuclear localization signals (NLSs) with the consensus sequence KR[X10-12]K. A total of 117 samples from initial TUR of human bladder carcinomas were analyzed. None of the patients had received chemotherapy or radiotherapy before pathological evaluation. Results: ATBF1 nuclear localization was regulated synergistically by three NLSs on ATBF1. The cytoplasmic fragments of ATBF1 lacked NLSs. Patients were divided into two groups according to positive nuclear staining of ATBF1, and significant differences in overall survival (P = 0.021) and intravesical recurrence-free survival (P = 0.013) were detected between ATBF1+ (n= 110) and ATBF1− (n=7) cases. Multivariate analysis revealed that ATBF1 staining was an independent prognostic factor for intravesical recurrence-free survival after adjusting for cellular grading and pathological staging (P = 0.008). Conclusions: Cleavage of ATBF1 leads to the cytoplasmic localization of ATBF1 fragments and downregulates nuclear ATBF1. Alterations in the subcellular localization of ATBF1 due to fragmentation of the protein are related to the malignant character of urothelial carcinoma. Pathological evaluation using anti-ATBF1 antibodies enabled the identification of highly malignant cases that had been overlooked at initial TUR. Nuclear localization of ATBF1 indicates better prognosis of urothelial carcinoma