Crustal recycling by subduction erosion in the central Mexican Volcanic Belt

Recycling of upper plate crust in subduction zones, or ‘subduction erosion’, is a major mechanism of crustal destruction at convergent margins. However, assessing the impact of eroded crust on arc magmas is difficult owing to the compositional similarity between the eroded crust, trench sediment and arc crustal basement that may all contribute to arc magma formation. Here we compare Sr–Nd–Pb–Hf and trace element data of crustal input material to Sr–Nd–Pb–Hf–He–O isotope chemistry of a well-characterized series of olivine-phyric, high-Mg# basalts to dacites in the central Mexican Volcanic Belt (MVB). Basaltic to andesitic magmas crystallize high-Ni olivines that have high mantle-like 3He/4He = 7–8 Ra and high crustal δ18Omelt = +6.3–8.5‰ implying their host magmas to be near-primary melts from a mantle infiltrated by slab-derived crustal components. Remarkably, their Hf–Nd isotope and Nd/Hf trace element systematics rule out the trench sediment as the recycled crust end member, and imply that the coastal and offshore granodiorites are the dominant recycled crust component. Sr–Nd–Pb–Hf isotope modeling shows that the granodiorites control the highly to moderately incompatible elements in the calc-alkaline arc magmas, together with lesser additions of Pb- and Sr-rich fluids from subducted mid-oceanic ridge basalt (MORB)-type altered oceanic crust (AOC). Nd–Hf mass balance suggests that the granodiorite exceeds the flux of the trench sediment by at least 9–10 times, corresponding to a flux of ⩾79–88 km3/km/Myr into the subduction zone. At an estimated thickness of 1500–1700 m, the granodiorite may buoyantly rise as bulk ‘slab diapirs’ into the mantle melt region and impose its trace element signature (e.g., Th/La, Nb/Ta) on the prevalent calc-alkaline arc magmas. Deep slab melting and local recycling of other slab components such as oceanic seamounts further diversify the MVB magmas by producing rare, strongly fractionated high-La magmas and a minor population of high-Nb magmas, respectively. Overall, the central MVB magmas inherit their striking geochemical diversity principally from the slab, thus emphasizing the importance of continental crust recycling in modern solid Earth relative to its new formation in modern subduction zones

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