Numerical modelling of Non-Transform Discontinuity geometry: Implication for ridge structure, volcano-tectonic fabric development and hydrothermal activity at segment ends.

Ocean ridge discontinuities partition and offset spreading centres at a range of scales. Large scale discontinuities (10's–100's km) are synonymous with first-order transform faults, which have well defined linear fault zone valleys. In contrast, Non-Transform Discontinuities (NTDs) are diffuse, smaller scale offsets (0 to b20 km), characterised by central basins or topographic highs. The geometry of NTD offsets can be categorised by the sense of offset, either right-stepping or left-stepping, and by the relative positions of the segment tips. The segment tip configurations include under-lapping, over-lapping or simple across-axis jumps or stepping in the ridge axis. In this study finite difference software is used to model segment geometry at a slow-spreading ridge under a normal tensile-stress within a homogeneous and isotropic medium. Along- and across-axis segment separations were varied incrementally for left- and right-stepping senses. The results show that the ratio of along-axis to across-axis segment tip separation is a dominant control of stress field rotation within an NTD. Features which most clearly show rotation within an NTD include basins and tectonically controlled constructional ridges. The obliquity of these features along with measurements of the surrounding fault fabrics are used as a way of observing and determining stress rotations within NTDs along the Central Indian Ridge (CIR). These rotations were used to obtain segment geometries from models where the central tensor showed an equivalentrotation. The results show that geometry has a profound effect on stress field rotation under which large- and small-scale volcanotectonic fabrics form. In addition, a shortfall of the predicted model tip relative to interpreted positions, along with morphology and observation of the ridge fabrics at the terminations to some segments, suggests the existence of a zone, broadly analogous to theprocess zone observed in fracture mechanics, which we call a damage zone. Given the criteria for the promotion of hydrothermal circulation, this damage zone would have a greater potential for hosting hydrothermal activity.<br/

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Mechanical control of oceanic plate boundary geometry

We present a global analysis of oceanic plate boundary geometry based on the mechanics of relative plate motion at mid-ocean ridges and transform faults. If the observed geometry formed by the first-order segmentation of oceanic plate boundaries represents a state of mechanical equilibrium, we find the relative strength of spreading ridges, and their bounding transform faults to be fundamental to its organisation. A consideration of power dissipation along adjacent lengths of spreading ridge and transform fault leads to a simple relationship between spreading obliquity and relative strength. Increased spreading rate is found to decrease the strength of spreading segments relative to transform faults. Proximity to an active hotspot reduces the relative strength of spreading ridges

Modelling of dripwater hydrology and hydrogeochemistry in a weakly karstified aquifer (Bath, UK): Implications for climate change studies

A better knowledge of dripwater hydrology in karst systems is needed to understand the palaeoclimate implications of temporal variations in Mg/Ca and Sr/Ca of calcareous cave deposits. Quantitative modelling of drip hydrology and hydrochemistry was undertaken at a disused limestone mine (Brown\u27s Folly Mine) in SW England overlain by 15 m of poorly karstified Jurassic limestones, with sub-vertical fracturing enhanced by proximity to an escarpment. Discharge was monitored at 15 sites intermittently from the beginning of 1996, and every 10–20 days from later 1996 to early 1998. Samples for hydrochemical parameters (pH, alkalinity, cations, anions, fluorescence) were taken corresponding to a sub-set of these data and supplemented by bedrock and soil sampling, limited continuously logged discharge, and soil water observations. Three sites, covering the range of discharge (approximately 1 μL s−1 to 1 ml s-1 maximum discharge) and hydrochemical behaviours, were studied in more detail. A quantitative flow model was constructed, based on two parallel unit hydrographs: responsive and relatively unresponsive to discharge events, respectively. The linear response and conservative mixing assumptions of the model were tested with hydrogeochemical data. Dripwaters at many of sites are characterized by evidence of prior calcite precipitation in the flowpath above the mine, which in the higher discharging sites diminishes at high flow. Also at low flow rates, dripwaters may access seepage reservoirs enriched in Mg and/or Sr, dependent on the site. The discharge at all three sites can be approximated by the flow model, but in each case, hydrochemical data show violations of the model assumptions. All sites show evidence of non-conservative mixing, and there are temporal discontinuities in behaviour, which may be stimulated by airlocks generated at low flow. Enhanced Mg/Ca and Sr/Ca often do relate to low-flow conditions, but the relationships between climate and hydrogeochemical response are non-linear

Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension.

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used ∼155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.Wellcome Trust (068545/Z/02)This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.365