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

United States Geological Survey Reports

From abstract: The Geysers-Clear Lake geothermal area lies within the central belt of the Franciscan assemblage in northern California. The structure of this terrane is characterized by northeast-dipping imbricate thrust slices that have been warped and cut by steeply dipping strike-slip and normal faults. Introduction of magma into the crust beneath the Geysers-Clear Lake area can be related to eastsoutheast extension accompanying northward propagation of the San Andreas transform system between the Clear Lake region and Cape Mendocino within the last 3 million years. The initiation of strike-slip faulting during this time terminated subduction of elements of the Farallon plate beneath North America as strike-slip motion was taken up along the Pacific-North American plate boundary. The mechanism for magma generation appears to require a heat source in the mantle that mixed mantle-derived melts with various crustal rocks. These crustal rocks may have included the Franciscan central and coastal belts, ophiolite, Great Valley sequence, and possibly middle and late Tertiary rocks subducted before initiation of strike-slip faulting

Straddling the tholeiitic/calc-alkaline transition: the effects of modest amounts of water on magmatic differentiation at Newberry Volcano, Oregon

Melting experiments have been performed at 1 bar (anhydrous) and 1- and 2-kbar H2O-saturated conditions to study the effect of water on the differentiation of a basaltic andesite. The starting material was a mafic pumice from the compositionally zoned tuff deposited during the ~75 ka caldera-forming eruption of Newberry Volcano, a rear-arc volcanic center in the central Oregon Cascades. Pumices in the tuff of Newberry caldera (TNC) span a continuous silica range from 53 to 74 wt% and feature an unusually high-Na2O content of 6.5 wt% at 67 wt% SiO2. This wide range of magmatic compositions erupted in a single event makes the TNC an excellent natural laboratory in which to study the conditions of magmatic differentiation. Our experimental results and mineral–melt hygrometers/thermometers yield similar estimates of pre-eruptive H2O contents and temperatures of the TNC liquids. The most primitive (mafic) basaltic andesites record a pre-eruptive H2O content of 1.5 wt% and a liquidus temperature of 1,060–1,070 °C at upper crustal pressure. This modest H2O content produces a distinctive fractionation trend that is much more enriched in Na, Fe, and Ti than the calc-alkaline trend typical of wetter arc magmas, but slightly less enriched in Fe and Ti than the tholeiitic trend of dry magmas. Modest H2O contents might be expected at Newberry Volcano given its location in the Cascade rear arc, and the same fractionation trend is also observed in the rim andesites of the rear-arc Medicine Lake volcano in the southern Cascades. However, the Na–Fe–Ti enrichment characteristic of modest H2O (1–2 wt%) is also observed to the west of Newberry in magmas erupted from the arc axis, such as the Shevlin Park Tuff and several lava flows from the Three Sisters. This shows that modest-H2O magmas are being generated directly beneath the arc axis as well as in the rear arc. Because liquid lines of descent are particularly sensitive to water content in the range of 0–3 wt% H2O, they provide a quantitative and reliable tool for precisely determining pre-eruptive H2O content using major-element data from pumices or lava flows. Coupled enrichment in Na, Fe, and Ti relative to the calc-alkaline trend is a general feature of fractional crystallization in the presence of modest amounts of H2O, which may be used to look for “damp” fractionation sequences elsewhere.National Science Foundation (U.S.) (NSF Grant EAR-0507486)National Science Foundation (U.S.) (NSF Grant EAR-1118598

Plagioclase zonation styles in hornblende gabbro inclusions from Little Glass Mountain, Medicine Lake volcano, California: implications for fractionation mechanisms and the formation of composition gaps

The rhyolite of Little Glass Mountain (73–74% SiO₂) is a single eruptive unit that contains inclusions of quenched andesite liquid (54–61% SiO₂) and partially crystalline cumulate hornblende gabbro (53–55% SiO₂). Based on previous studies, the quenched andesite inclusions and host rhyolite lava are related to one another through fractional crystallization and represent an example of a fractionation-generated composition gap. The hornblende gabbros represent the cumulate residue associated with the rhyolite-producing and composition gap-forming fractionation event. This study combines textural (Nomarski Differential Interference Contrast, NDIC, imaging), major element (An content) and trace element (Mg, Fe, Sr, K, Ti, Ba) data on the style of zonation of plagioclase crystals from representative andesite and gabbro inclusions, to assess the physical environment in which the fractionation event and composition gap formation took place. The andesite inclusions (54–61% SiO₂) are sparsely phyric with phenocrysts of plagioclase, augite and Fe-oxide±olivine, +/–orthopyroxene, +/–hornblende set within a glassy to crystalline matrix. The gabbro cumulates (53–55% SiO₂) consist of an interconnected framework of plagioclase, augite, olivine, orthopyroxene, hornblende and Fe-oxide along with highly vesicular interstitial glass (70–74% SiO₂). The gabbros record a two-stage crystallization history of plagioclase+olivine+augite (Stage I) followed by plagioclase+orthopyroxene+ hornblende+Fe-oxide (Stage II). Texturally, the plagioclase crystals in the andesite inclusions are characterized by complex, fine-scale oscillatory zonation and abundant dissolution surfaces. Compositionally (An content) the crystals are essentially unzoned from core-to-rim. These features indicate growth within a dynamic (convecting?), reservoir of andesite magma. In contrast, the plagioclase crystals in the gabbros are texturally smooth and featureless with strong normal zonation from An₇₄ at the core to around An₃₀. K, and Ba abundances increase and Mg abundances decrease steadily towards the rim. Ti, Fe, and Sr abundances increase and then decrease towards the rim. The trace element variations are fully consistent with the two-stage crystallization sequence inferred from the gabbro mineralogy. These results indicate progressive closed-system in situ crystallization in a quiescent magmatic boundary layer environment located along the margins of the andesite magma body. The fractional crystallization that generated the host rhyolite lava is one of inward solidification of a crystallizing boundary layer followed by melt extraction and accumulation of highly evolved interstitial liquid. This mechanism explains the formation of the composition gap between parental andesite and rhyolite magma compositions

Depths and temperatures of <10.5 Ma mantle melting and the lithosphere-asthenosphere boundary below southern Oregon and northern California

Plagioclase and spinel lherzolite thermometry and barometry are applied to an extensive geochemical dataset of young (<10.5 Ma) primitive basaltic lavas from across Oregon's High Lava Plains, California's Modoc Plateau, and the central-southern Cascades volcanic arc to calculate the depths and temperatures of mantle melting. This study focuses on basalts with low pre-eruptive H2O contents that are little fractionated near-primary melts of mantle peridotite (i.e., basalts thought to be products of anhydrous decompression mantle melting). Calculated minimum depths of nominally anhydrous melt extraction are 40–58 km below Oregon's High Lava Plains, 41–51 km below the Modoc Plateau, and 37–60 km below the central and southern Cascades arc. The calculated depths are very close to Moho depths as determined from a number of regional geophysical studies and suggest that the geophysical Moho and lithosphere-asthenosphere boundary in this region are located in very close proximity to one another (within 5–10 km). The basalts originated at 1185–1383°C and point to a generally warm mantle beneath this area but not one hot enough to obviously require a plume contribution. Our results, combined with a range of other geologic, geophysical, and geochemical constraints, are consistent with a regional model whereby anhydrous mantle melting over the last 10.5 Ma in a modern convergent margin and back arc was driven by subduction-induced corner flow in the mantle wedge, and to a lesser extent, toroidal flow around the southern edge of the subducting Juan de Fuca and Gorda plates, and crustal extension-related upwelling of the shallow mantle

Depths and temperatures of <10.5 Ma mantle melting and the lithosphere-asthenosphere boundary below southern Oregon and northern California

Plagioclase and spinel lherzolite thermometry and barometry are applied to an extensive geochemical dataset of young (<10.5 Ma) primitive basaltic lavas from across Oregon's High Lava Plains, California's Modoc Plateau, and the central-southern Cascades volcanic arc to calculate the depths and temperatures of mantle melting. This study focuses on basalts with low pre-eruptive H2O contents that are little fractionated near-primary melts of mantle peridotite (i.e., basalts thought to be products of anhydrous decompression mantle melting). Calculated minimum depths of nominally anhydrous melt extraction are 40–58 km below Oregon's High Lava Plains, 41–51 km below the Modoc Plateau, and 37–60 km below the central and southern Cascades arc. The calculated depths are very close to Moho depths as determined from a number of regional geophysical studies and suggest that the geophysical Moho and lithosphere-asthenosphere boundary in this region are located in very close proximity to one another (within 5–10 km). The basalts originated at 1185–1383°C and point to a generally warm mantle beneath this area but not one hot enough to obviously require a plume contribution. Our results, combined with a range of other geologic, geophysical, and geochemical constraints, are consistent with a regional model whereby anhydrous mantle melting over the last 10.5 Ma in a modern convergent margin and back arc was driven by subduction-induced corner flow in the mantle wedge, and to a lesser extent, toroidal flow around the southern edge of the subducting Juan de Fuca and Gorda plates, and crustal extension-related upwelling of the shallow mantle