95 research outputs found

    Foraminiferal and sedimentological evidence far uplift of the deep-sea floor, Gorda Rise, northeastern Pacific

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    Displaced benthic Foraminifera in semiconsolidated clayey sandstone from the Gorda Rise provide evidence for uplift of the deep-sea floor. The sediment was deposited by turbidity currents on the floor of the Escanaba Trough (the axial valley of the Gorda Rise) from a sublittoral source on the continental margin to the east...

    EC00-2540 Field Records for Restricted Use Pesticide Applications and Integrated Crop Management by Private Applicators

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    Private applicators must record their restricted use pesticide (RUP) applications, as required by the Food, Agriculture, Conservation and Trade (FACT) Act of 1990. The USDA Agricultural Marketing Service administers this activity. In Nebraska, RUP application records must be maintained for three years from the date of application. The certified pesticide applicator should retain these RUP records, but must be able to make them accessible for copying by authorized representatives. This booklet is a suggested guide for preliminary or final RUP application records

    Long-term treatment with selective PI3Kδ inhibitor leniolisib in adults with activated PI3Kδ syndrome

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    Activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) is an inborn error of immunity that manifests as immune deficiency and dysregulation; symptoms include frequent infections and lymphoproliferation. In our dose-finding and phase 3 placebo-controlled trials, treatment with the selective PI3Kδ inhibitor leniolisib reduced lymphoproliferation and normalized lymphocyte subsets. Here, we present 6 years of follow-up from the 6 adult patients in the original dose-finding trial receiving leniolisib. We used data from the ongoing open-label extension study, which was supplemented at later time points by investigators, including health-related quality of life (HRQoL) assessed through a clinician-reported questionnaire. We observed improvements in HRQoL: 5 of 6 patients experienced an increase in physical capabilities and socialization, and a decrease in prescribed medications. Immune subsets improved in all patients: mean transitional B-cell levels decreased from 38.17% to 2.47% and the CD4:CD8 T-cell ratio normalized to 1.11. Manifestations seen before and within the first year of leniolisib exposure, such as infections and gastrointestinal conditions, attenuated after year 2, with few new conditions emerging out to year 6. Thrombocytopenia or lymphopenia remained present in half of patients at year 6. Of 83 adverse events through year 5, 90.36% were grade 1; none were grade 4/5 nor deemed leniolisib related. Collectively, we saw an enhancement in HRQoL as well as durable changes in lymphocyte subsets and clinical manifestations, further supporting the use of leniolisib as a long-term therapeutic option for the treatment of APDS. This trial was registered at www.ClinicalTrials.gov as #NCT02859727.</p

    Interim analysis:Open-label extension study of leniolisib for patients with APDS

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    Background: Activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS; or p110δ-activating mutations causing senescent T cells, lymphadenopathy, and immunodeficiency) is an inborn error of immunity caused by PI3Kδ hyperactivity. Resultant immune deficiency and dysregulation lead to recurrent sinopulmonary infections, herpes viremia, autoimmunity, and lymphoproliferation. Objective: Leniolisib, a selective PI3Kδ inhibitor, demonstrated favorable impact on immune cell subsets and lymphoproliferation over placebo in patients with APDS over 12 weeks. Here, we report results from an interim analysis of an ongoing open-label, single-arm extension study. Methods: Patients with APDS aged 12 years or older who completed NCT02435173 or had previous exposure to PI3Kδ inhibitors were eligible. The primary end point was safety, assessed via investigator-reported adverse events (AEs) and clinical/laboratory evaluations. Secondary and exploratory end points included health-related quality of life, inflammatory markers, frequency of infections, and lymphoproliferation. Results: Between September 2016 and August 2021, 37 patients (median age, 20 years; 42.3% female) were enrolled. Of these 37 patients, 26, 9, and 2 patients had previously received leniolisib, placebo, or other PI3Kδ inhibitors, respectively. At the data cutoff date (December 13, 2021), median leniolisib exposure was 102 weeks. Overall, 32 patients (87%) experienced an AE. Most AEs were grades 1 to 3; none were grade 4. One patient with severe baseline comorbidities experienced a grade 5 AE, determined as unrelated to leniolisib treatment. While on leniolisib, patients had reduced annualized infection rates (P =.004), and reductions in immunoglobulin replacement therapy occurred in 10 of 27 patients. Other observations include reduced lymphadenopathy and splenomegaly, improved cytopenias, and normalized lymphocyte subsets. Conclusions: Leniolisib was well tolerated and maintained durable outcomes with up to 5 years of exposure in 37 patients with APDS. ClinicalTrials.gov identifier: NCT02859727.</p

    Fluid venting in the eastern Aleutian subduction zone

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    Fluid venting has been observed along 800 km of the Alaska convergent margin. The fluid venting sites are located near the deformation front, are controlled by subsurface structures, and exhibit the characteristics of cold seeps seen in other convergent margins. The more important characteristics include (1) methane plumes in the lower water column with maxima above the seafloor which are traceable to the initial deformation ridges; (2) prolific colonies of vent biota aligned and distributed in patches controlled by fault scarps, over‐steepened folds or outcrops of bedding planes; (3) calcium carbonate and barite precipitates at the surface and subsurface of vents; and (4) carbon isotope evidence from tissue and skeletal hard parts of biota, as well as from carbonate precipitates, that vents expel either methane‐ or sulfide‐dominated fluids. A biogeochemical approach toward estimating fluid flow rates from individual vents based on oxygen flux measurements and vent fluid analysis indicates a mean value of 5.5±0.7 L m−2 d−1 for tectonics‐induced water flow [Wallmann et al., 1997b]. A geophysical estimate of dewatering from the same area [von Huene et al., 1997] based on sediment porosity reduction shows a fluid loss of 0.02 L m−2 d−1 for a 5.5 km wide converged segment near the deformation front. Our video‐guided surveys have documented vent biota across a minimum of 0.1% of the area of the convergent segment off Kodiak Island; hence an average rate of 0.006 L m−2 d−1 is estimated from the biogeochemical approach. The two estimates for tectonics‐induced water flow from the accretionary prism are in surprisingly good agreement

    Crustal structure of the Peruvian continental margin from wide-angle seismic studies

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    Active seismic investigations along the Pacific margin off Peru were carried out using ocean bottom hydrophones and seismometers. The structure and the P-wave velocities of the obliquely subducting oceanic Nazca Plate and overriding South American Plate from 8°S to 15°S were determined by modelling the wide-angle seismic data combined with the analysis of reflection seismic data. Three detailed cross-sections of the subduction zone of the Peruvian margin and one strike-line across the Lima Basin are presented here. The oceanic crust of the Nazca Plate, with a thin pelagic sediment cover, ranging from 0–200 m, has an average thickness of 6.4 km. At 8°S it thins to 4 km in the area of Trujillo Trough, a graben-like structure. Across the margin, the plate boundary can be traced to 25 km depth. As inferred from the velocity models, a frontal prism exists adjacent to the trench axis and is associated with the steep lower slope. Terrigeneous sediments are proposed to be transported downslope due to gravitational forces and comprise the frontal prism, characterized by low seismic P-wave velocities. The lower slope material accretes against a backstop structure, which is defined by higher seismic P-wave velocities, 3.5–6.0 km s−1. The large variations in surface slope along one transect may reflect basal removal of upper plate material, thus steepening the slope surface. Subduction processes along the Peruvian margin are dominated by tectonic erosion indicated by the large margin taper, the shape and bending of the subducting slab, laterally varying slope angles and the material properties of the overriding continental plate. The erosional mechanisms, frontal and basal erosion, result in the steepening of the slope and consequent slope failure

    Do trench sediments affect great earthquake occurrence in subduction zones?

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    Seismic energy release is dominated by the underthrusting earthquakes in subduction zones, and this energy release is further concentrated in a few subduction zones. While some subduction zones are characterized by the occurrence of great earthquakes, others are relatively aseismic. This variation in maximum earthquake size between subduction zones is one of the most important features of global seismicity. Previous work has shown that the variation in maximum earthquake size is correlated with the variation in two other subduction zone properties: age of the subducting lithosphere and convergence rate. These two properties do not explain all the variance in maximum earthquake size. I propose that a third subduction zone property, “trench sediments”, explains part of the remaining variance in maximum earthquake size. Subduction zones are divided into two groups: (1) those with excess trench sediments, and (2) those with horst and graben structure at the trench. Thirteen of the 19 largest subduction zone events, including the three largest, occur in zones with excess trench sediments. About half the zones with excess trench sediments are characterized by great earthquake occurrence. Most of the other zones with excess trench sediments but without great earthquakes are predicted to have small earthquakes by the age-rate correlation. Two notable exceptions are the Oregon-Washington and Middle America zones. Overall, the presence of excess trench sediments appears to enhance great earthquake occurrence. One speculative physical mechanism that connects trench sediments and earthquake size is that excess trench sediments are associated with the subduction of a coherent sedimentary layer, which at elevated temperature and pressure, forms a homogeneous and strong contact zone between the plates.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43133/1/24_2004_Article_BF00874629.pd
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