88 research outputs found

    In situ measurement of fluid flow from cold seeps at active continental margins

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    In situ measurement of fluid flow rates from active margins is an important parameter in evaluating dissolved mass fluxes and global geochemical balances as well as tectonic dewatering during developments of accretionary prisms. We have constructed and deployed various devices that allow for the direct measurement of this parameter. An open bottom barrel with an exhaust port at the top and equipped with a mechanical flowmeter was initially used to measure flow rates in the Cascadia accretionary margin during an Alvin dive program in 1988. Sequentially activated water bottles inside the barrel sampled the increase of venting methane in the enclosed body of water. Subsequently, a thermistor flowmeter was developed to measure flow velocities from cold seeps. It can be used to measure velocities between 0.01 and 50 cm s−1, with a response time of 200 ms. It was deployed again by the submersible Alvin in visits to the Cascadia margin seeps (1990) and in conjunction with sequentially activated water bottles inside the barrel. We report the values for the flow rates based on the thermistor flowmeter and estimated from methane flux calculations. These results are then compared with the first measurement at Cascadia margin employing the mechanical flowmeter. The similarity between water flow and methane expulsion rates over more than one order of magnitude at these sites suggests that the mass fluxes obtained by our in situ devices may be reasonably realistic values for accretionary margins. These values also indicate an enormous variability in the rates of fluid expulsion within the same accretionary prism. Finally, during a cruise to the active margin off Peru, another version of the same instrument was deployed via a TV-controlled frame within an acoustic transponder net from a surface ship, the R.V. Sonne. The venting rates obtained with the thermistor flowmeter used in this configuration yielded a value of 4411 m−2 day−1 at an active seep on the Peru slope. The ability for deployment of deep-sea instruments capable of measuring fluid flow rates and dissolved mass fluxes from conventional research vessels will allow easier access to these seep sites and a more widespread collection of the data needed to evaluate geochemical processes resulting from venting at cold seeps on a global basis. Comparison of the in situ flow rates from steady-state compactive dewatering models differ by more than 4 orders of magnitude. This implies that only a small area of the margin is venting and that there must be recharge zones associated with venting at convergent margin

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

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    Background: Activated phosphoinositide 3-kinase delta (PI3KΎ) syndrome (APDS; or p110Ύ-activating mutations causing senescent T cells, lymphadenopathy, and immunodeficiency) is an inborn error of immunity caused by PI3KΎ hyperactivity. Resultant immune deficiency and dysregulation lead to recurrent sinopulmonary infections, herpes viremia, autoimmunity, and lymphoproliferation. Objective: Leniolisib, a selective PI3KΎ 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 PI3KΎ 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 PI3KΎ 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

    Development of a genotyping microarray for Usher syndrome

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    BACKGROUND: Usher syndrome, a combination of retinitis pigmentosa (RP) and sensorineural hearing loss with or without vestibular dysfunction, displays a high degree of clinical and genetic heterogeneity. Three clinical subtypes can be distinguished, based on the age of onset and severity of the hearing impairment, and the presence or absence of vestibular abnormalities. Thus far, eight genes have been implicated in the syndrome, together comprising 347 protein-coding exons. METHODS: To improve DNA diagnostics for patients with Usher syndrome, we developed a genotyping microarray based on the arrayed primer extension (APEX) method. Allele-specific oligonucleotides corresponding to all 298 Usher syndrome-associated sequence variants known to date, 76 of which are novel, were arrayed. RESULTS: Approximately half of these variants were validated using original patient DNAs, which yielded an accuracy of >98%. The efficiency of the Usher genotyping microarray was tested using DNAs from 370 unrelated European and American patients with Usher syndrome. Sequence variants were identified in 64/140 (46%) patients with Usher syndrome type I, 45/189 (24%) patients with Usher syndrome type II, 6/21 (29%) patients with Usher syndrome type III and 6/20 (30%) patients with atypical Usher syndrome. The chip also identified two novel sequence variants, c.400C>T (p.R134X) in PCDH15 and c.1606T>C (p.C536S) in USH2A. CONCLUSION: The Usher genotyping microarray is a versatile and affordable screening tool for Usher syndrome. Its efficiency will improve with the addition of novel sequence variants with minimal extra costs, making it a very useful first-pass screening tool

    Volcanic CO2 output at the Central American subduction zone inferred from melt inclusions in olivine crystals from mafic tephras

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    The volatile contents of olivine‐hosted (Fo89–71) melt inclusion glasses in rapidly quenched mafic tephras from volcanic front volcanoes of the Central American Volcanic Arc (CAVA) in Guatemala, Nicaragua, and Costa Rica, were analyzed by secondary ion mass spectrometry (SIMS) in order to derive the minimum eruptive output of CO2, along with H2O, Cl, and S. Details of the analytical method are provided that establish melt inclusion CO2 analyses with the Cameca ims6f at the Helmholtz Centre Potsdam. The highest CO2 concentrations (up to 1800 mg/g) are observed in Nicaraguan samples, while melt inclusions from Guatemala and Costa Rica have CO2 contents between 50 and 500 mg/g. CO2 does not positively covary with sediment/slab fluid tracers such as Ba/La, Ba/Th, or U/La. Instead, the highest CO2 concentrations occur in the inclusions with the most depleted incompatible element compositions and low H2O, approaching the composition of mid‐ocean ridge basalts (MORBs), whereas the most H2O‐rich inclusions are relatively CO2‐poor (<800 mg/g). This suggests that CO2 degassing was more extensive in the melts with the highest slab contribution. CO2/Nb ratios in the least degassed CAVA melt inclusions are similar to those of primitive MORBs. These are interpreted here as recording a minimum CO2 output rate from the mantle wedge, which amounts to 2.8 × 104 g/s for the ∌1100 km long CAVA. Previously published estimates from quiescent degassing and numerical modeling, which also encompassed the slab contribution, are 3 times higher. This comparison allows us to estimate the proportion of the total CO2 output derived from the mantle wedge

    Oregon Subduction Zone: Venting, Fauna, and Carbonates

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    Transects of the submersible Alvin across rock outcrops in the Oregon subduction zone have furnished information on the structural and stratigraphic framework of this accretionary complex. Communities of clams and tube worms, and authigenic carbonate mineral precipitates, are associated with venting sites of cool fluids located on a fault-bend anticline at a water depth of 2036 meters. The distribution of animals and carbonates suggests up-dip migration of fluids from both shallow and deep sources along permeable strata or fault zones within these clastic deposits. Methane is enriched in the water column over one vent site, and carbonate minerals and animal tissues are highly enriched in carbon-12. The animals use methane as an energy and food source in symbiosis with microorganisms. Oxidized methane is also the carbon source for the authigenic carbonates that cement the sediments of the accretionary complex. The animal communities and carbonates observed in the Oregon subduction zone occur in strata as old as 2.0 million years and provide criteria for identifying other localities where modern and ancient accreted deposits have vented methane, hydrocarbons, and other nutrient-bearing fluids

    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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