73 research outputs found
Evaluating How Well Active Fault Mapping Predicts earthquake surface-rupture locations
Earthquake surface-fault rupture location uncertainty is a key factor in fault displacement hazard analysis and informs hazard and risk mitigation strategies. Geologists often predict future rupture locations from fault mapping based on the geomorphology interpreted from remote-sensing data sets. However, surface processes can obscure fault location, fault traces may be mapped in error, and a future rupture may not break every fault trace. We assessed how well geomorphology-based fault mapping predicted surface ruptures for seven earthquakes: 1983 M 6.9 Borah Peak, 2004 M 6.0 Parkfield, 2010 M 7.2 El MayorâCucapah, 2011 M 6.7 Fukushima-Hamadori, 2014 M 6.0 South Napa, 2016 M 7.8 Kaikoura, and 2016 M 7 Kumamoto. We trained geoscience students to produce active fault maps using topography and imagery acquired before the earthquakes. A geologic professional completed a âcontrolâ map. Mappers used a new âgeomorphic indicator rankingâ approach to rank fault confidence based on geomorphologic landforms. We determined the accuracy of the mapped faults by comparing the fault maps to published rupture maps. We defined predicted ruptures as ruptures near a fault (50â200 m, depending on the fault confidence) that interacted with the landscape in a similar way to the fault. The mapped faults predicted between 12% to 68% of the principal rupture length for the studied earthquakes. The median separation distances between predicted ruptures and strong, distinct, or weak faults were 15â30 m. Our work highlights that mapping future fault ruptures is an underappreciated challenge of fault displacement hazard analysisâeven for expertsâwith implications for risk management, engineering site assessments, and fault exclusion zones
Optimal protamine dosing after cardiopulmonary bypass: The PRODOSE adaptive randomised controlled trial.
BackgroundThe dose of protamine required following cardiopulmonary bypass (CPB) is often determined by the dose of heparin required pre-CPB, expressed as a fixed ratio. Dosing based on mathematical models of heparin clearance is postulated to improve protamine dosing precision and coagulation. We hypothesised that protamine dosing based on a 2-compartment model would improve thromboelastography (TEG) parameters and reduce the dose of protamine administered, relative to a fixed ratio.Methods and findingsWe undertook a 2-stage, adaptive randomised controlled trial, allocating 228 participants to receive protamine dosed according to a mathematical model of heparin clearance or a fixed ratio of 1 mg of protamine for every 100 IU of heparin required to establish anticoagulation pre-CPB. A planned, blinded interim analysis was undertaken after the recruitment of 50% of the study cohort. Following this, the randomisation ratio was adapted from 1:1 to 1:1.33 to increase recruitment to the superior arm while maintaining study power. At the conclusion of trial recruitment, we had randomised 121 patients to the intervention arm and 107 patients to the control arm. The primary endpoint was kaolin TEG r-time measured 3 minutes after protamine administration at the end of CPB. Secondary endpoints included ratio of kaolin TEG r-time pre-CPB to the same metric following protamine administration, requirement for allogeneic red cell transfusion, intercostal catheter drainage at 4 hours postoperatively, and the requirement for reoperation due to bleeding. The trial was listed on a clinical trial registry (ClinicalTrials.gov Identifier: NCT03532594). Participants were recruited between April 2018 and August 2019. Those in the intervention/model group had a shorter mean kaolin r-time (6.58 [SD 2.50] vs. 8.08 [SD 3.98] minutes; p = 0.0016) post-CPB. The post-protamine thromboelastogram of the model group was closer to pre-CPB parameters (median pre-CPB to post-protamine kaolin r-time ratio 0.96 [IQR 0.78-1.14] vs. 0.75 [IQR 0.57-0.99]; p 120 kg, and patients requiring therapeutic hypothermia to ConclusionsUsing a mathematical model to guide protamine dosing in patients following CPB improved TEG r-time and reduced the dose administered relative to a fixed ratio. No differences were detected in postoperative mediastinal/pleural drainage or red blood cell transfusion requirement in our cohort of low-risk patients.Trial registrationClinicalTrials.gov Unique identifier NCT03532594
Analyzing high resolution topography for advancing the understanding of mass and energy transfer through landscapes: A review
International audienceThe study of mass and energy transfer across landscapes has recently evolved to comprehensive considerations acknowledging the role of biota and humans as geomorphic agents, as well as the importance of small-scale landscape features. A contributing and supporting factor to this evolution is the emergence over the last two decades of technologies able to acquire high resolution topography (HRT) (meter and sub-meter resolution) data. Landscape features can now be captured at an appropriately fine spatial resolution at which surface processes operate; this has revolutionized the way we study Earth-surface processes. The wealth of information contained in HRT also presents considerable challenges. For example, selection of the most appropriate type of HRT data for a given application is not trivial. No definitive approach exists for identifying and filtering erroneous or unwanted data, yet inappropriate filtering can create artifacts or eliminate/distort critical features. Estimates of errors and uncertainty are often poorly defined and typically fail to represent the spatial heterogeneity of the dataset, which may introduce bias or error for many analyses. For ease of use, gridded products are typically preferred rather than the more information-rich point cloud representations. Thus many users take advantage of only a fraction of the available data, which has furthermore been subjected to a series of operations often not known or investigated by the user. Lastly, standard HRT analysis work-flows are yet to be established for many popular HRT operations, which has contributed to the limited use of point cloud data.In this review, we identify key research questions relevant to the Earth-surface processes community within the theme of mass and energy transfer across landscapes and offer guidance on how to identify the most appropriate topographic data type for the analysis of interest. We describe the operations commonly performed from raw data to raster products and we identify key considerations and suggest appropriate work-flows for each, pointing to useful resources and available tools. Future research directions should stimulate further development of tools that take advantage of the wealth of information contained in the HRT data and address the present and upcoming research needs such as the ability to filter out unwanted data, compute spatially variable estimates of uncertainty and perform multi-scale analyses. While we focus primarily on HRT applications for mass and energy transfer, we envision this review to be relevant beyond the Earth-surface processes community for a much broader range of applications involving the analysis of HRT
Early human impacts and ecosystem reorganization in southern-central Africa
Modern Homo sapiens engage in substantial ecosystem modification, but it is difficult to detect the origins or early consequences of these behaviors. Archaeological, geochronological, geomorphological, and paleoenvironmental data from northern Malawi document a changing relationship between forager presence, ecosystem organization, and alluvial fan formation in the Late Pleistocene. Dense concentrations of Middle Stone Age artifacts and alluvial fan systems formed after ca. 92 thousand years ago, within a paleoecological context with no analog in the preceding half-million-year record. Archaeological data and principal coordinates analysis indicate that early anthropogenic fire relaxed seasonal constraints on ignitions, influencing vegetation composition and erosion. This operated in tandem with climate-driven changes in precipitation to culminate in an ecological transition to an early, pre-agricultural anthropogenic landscape.info:eu-repo/semantics/publishedVersio
Maternal age effects on myometrial expression of contractile proteins, uterine gene expression, and contractile activity during labor in the rat
Advanced maternal age of first time pregnant mothers is associated with prolonged and dysfunctional labor and significant risk of emergency cesarean section. We investigated the influence of maternal age on myometrial contractility, expression of contractile associated proteins (CAPs), and global gene expression in the parturient uterus. Female Wistar rats either 8 (YOUNG n = 10) or 24 (OLDER n = 10) weeks old were fed laboratory chow, mated, and killed during parturition. Myometrial strips were dissected to determine contractile activity, cholesterol (CHOL) and triglycerides (TAG) content, protein expression of connexin-43 (GJA1), prostaglandin endoperoxide synthase 2 (PTGS2), and caveolin 1 (CAV-1). Maternal plasma concentrations of prostaglandins PGE2, PGF2a, and progesterone were determined by RIA. Global gene expression in uterine samples was compared using Affymetrix Genechip Gene 2.0 ST arrays and Ingenuity Pathway analysis (IPA). Spontaneous contractility in myometrium exhibited by YOUNG rats was threefold greater than OLDER animals (P < 0.027) but maternal age had no significant effect on myometrial CAP expression, lipid profiles, or pregnancy related hormones. OLDER myometrium increased contractile activity in response to PGF2a, phenylephrine, and carbachol, a response absent in YOUNG rats (all P < 0.002). Microarray analysis identified that maternal age affected expression of genes related to immune and inflammatory responses, lipid transport and metabolism, steroid metabolism, tissue remodeling, and smooth muscle contraction. In conclusion YOUNG laboring rat myometrium seems primed to contract maximally, whereas activity is blunted in OLDER animals and requires stimulation to meet contractile potential. Further work investigating maternal age effects on myometrial function is required with focus on lipidmetabolism and inflammatory pathways
Oligosaccharyltransferase Inhibition Induces Senescence in RTK-Driven Tumor Cells
Asparagine (N)-linked glycosylation is a protein modification critical for glycoprotein folding, stability, and cellular localization. To identify small molecules that inhibit new targets in this biosynthetic pathway, we initiated a cell-based high throughput screen and lead compound optimization campaign that delivered a cell permeable inhibitor (NGI-1). NGI-1 targets the oligosaccharyltransferase (OST), a hetero-oligomeric enzyme that exists in multiple isoforms and transfers oligosaccharides to recipient proteins. In non-small cell lung cancer cells NGI-1 blocks cell surface localization and signaling of the EGFR glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or FGFR) for survival. In these cell lines OST inhibition causes cell cycle arrest accompanied by induction of p21, autofluorescence, and changes in cell morphology; all hallmarks of senescence. These results identify OST inhibition as a potential therapeutic approach for treating receptor tyrosine kinase-dependent tumors and provides a chemical probe for reversibly regulating N-linked glycosylation in mammalian cells
Structure and bonding in three-coordinate N-heterocyclic carbene adducts of iron(ii) bis(trimethylsilyl)amide
Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic
This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic
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