Provenance and Paleogeography of the 25-17 Ma Rainbow Gardens Formation: Evidence for Tectonic Activity at Ca. 19 Ma and Internal Drainage rather than Throughgoing Paleorivers on the Southwestern Colorado Plateau

The paleogeographic evolution of the Lake Mead region of southern Nevada and northwest Arizona is crucial to understanding the geologic history of the U.S. Southwest, including the evolution of the Colorado Plateau and formation of the Grand Canyon. The ca. 25–17 Ma Rainbow Gardens Formation in the Lake Mead region, the informally named, roughly coeval Jean Conglomerate, and the ca. 24–19 Ma Buck and Doe Conglomerate southeast of Lake Mead hold the only stratigraphic evidence for the Cenozoic pre-extensional geology and paleogeography of this area. Building on prior work, we present new sedimentologic and stratigraphic data, including sandstone provenance and detrital zircon data, to create a more detailed paleogeographic picture of the Lake Mead, Grand Wash Trough, and Hualapai Plateau region from 25 to 18 Ma. These data confirm that sediment was sourced primarily from Paleozoic strata exposed in surrounding Sevier and Laramide uplifts and active volcanic fields to the north. In addition, a distinctive signal of coarse sediment derived from Proterozoic crystalline basement first appeared in the southwestern corner of the basin ca. 25 Ma at the beginning of Rainbow Gardens Formation deposition and then prograded north and east ca. 19 Ma across the southern half of the basin. Regional thermochronologic data suggest that Cretaceous deposits likely blanketed the Lake Mead region by the end of Sevier thrusting. Post-Laramide northward cliff retreat off the Kingman/Mogollon uplifts left a stepped erosion surface with progressively younger strata preserved northward, on which Rainbow Gardens Formation strata were deposited. Deposition of the Rainbow Gardens Formation in general and the 19 Ma progradational pulse in particular may reflect tectonic uplift events just prior to onset of rapid extension at 17 Ma, as supported by both thermochronology and sedimentary data. Data presented here negate the California and Arizona River hypotheses for an “old” Grand Canyon and also negate models wherein the Rainbow Gardens Formation was the depocenter for a 25–18 Ma Little Colorado paleoriver flowing west through East Kaibab paleocanyons. Instead, provenance and paleocurrent data suggest local to regional sources for deposition of the Rainbow Gardens Formation atop a stripped low-relief western Colorado Plateau surface and preclude any significant input from a regional throughgoing paleoriver entering the basin from the east or northeast

Evaluating the Shinumo-Sespe drainage connection: Arguments against the “old” (70–17 Ma) Grand Canyon models for Colorado Plateau drainage evolution

The provocative hypothesis that the Shinumo Sandstone in the depths of Grand Canyon was the source for clasts of orthoquartzite in conglomerate of the Sespe Formation of coastal California, if verified, would indicate that a major river system flowed southwest from the Colorado Plateau to the Pacific Ocean prior to opening of the Gulf of California, and would imply that Grand Canyon had been carved to within a few hundred meters of its modern depth at the time of this drainage connection. The proposed Eocene Shinumo-Sespe connection, however, is not supported by detrital zircon nor paleomagnetic-inclination data and is refuted by thermochronology that shows that the Shinumo Sandstone of eastern Grand Canyon was \u3e60 °C (∼1.8 km deep) and hence not incised at this time. A proposed 20 Ma (Miocene) Shinumo-Sespe drainage connection based on clasts in the Sespe Formation is also refuted. We point out numerous caveats and non-unique interpretations of paleomagnetic data from clasts. Further, our detrital zircon analysis requires diverse sources for Sespe clasts, with better statistical matches for the four “most-Shinumo-like” Sespe clasts with quartzites of the Big Bear Group and Ontario Ridge metasedimentary succession of the Transverse Ranges, Horse Thief Springs Formation from Death Valley, and Troy Quartzite of central Arizona. Diverse thermochronologic and geologic data also refute a Miocene river pathway through western Grand Canyon and Grand Wash trough. Thus, Sespe clasts do not require a drainage connection from Grand Canyon or the Colorado Plateau and provide no constraints for the history of carving of Grand Canyon. Instead, abundant evidence refutes the “old” (70–17 Ma) Grand Canyon models and supports a \u3c6 Ma Grand Canyon

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

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

Criteria for Recognition of Subducted (Orocopia) Schist in Western Arizona

INVITED POSTER: The Orocopia Schist is a latest Cretaceous low-angle subduction channel, part of a larger subduction complex, the Pelona-Orocopia-Rand Schist (PORS), that underlies much of southern California and southwest Arizona (Fig. 1; Jacobson et al. 1988, 2007, 2011; Haxel et al. 2002; Chapman 2016). The principal locus of Orocopia Schist, the Chocolate Mountains anticlinorium extending from the Orocopia Mountains east to Neversweat Ridge, has been known since the mid 1970s (Haxel and Dillon 1978). Recently, two more exposures of the oceanic Orocopia Schist have been found at isolated localities farther inland in southwest Arizona: Cemetery Ridge (Haxel et al. 2015, 2018b, 2021; Jacobson et al. 2017) and northern Plomosa Mountains (Strickland et al. 2017, 2018; Seymour et al. 2018). These discoveries raise the possibility that additional inboard areas of Orocopia Schist have yet to be found. Hence a review of criteria for recognition of Orocopia Schist is warranted.Documents in the AZGS Documents Repository collection are made available by the Arizona Geological Survey (AZGS) and the University Libraries at the University of Arizona. For more information about items in this collection, please contact [email protected]

Geologic Map and Geochronology of the Picacho, Picacho NW, Picacho SW, and Hidden Valley 7.5-Minute Quadrangles, Arizona and California

This report accompanies a digital geologic map of the Picacho, Picacho SW, Picacho NW, and Hidden Valley 7.5-minute quadrangles — the four quadrants of the Picacho 15-minute quadrangle. The map area is located within the central and south-ern Trigo Mountains, Arizona, and southeastern Chocolate Mountains, California and is dominated by stratigraphically and structurally complex Mesozoic and Cenozoic rocks relevant to understanding the geologic evolution of the U.S. Southwest more broadly. The report provides descriptions of the geologic map units, their environments of formation, age constraints, deformational history, and regional correlations. It also includes a brief summary of metallic ore deposits within the map area, as well as a selective bibliography of publications on ore deposits in and adjacent to the map area.Documents in the AZGS Documents Repository collection are made available by the Arizona Geological Survey (AZGS) and the University Libraries at the University of Arizona. For more information about items in this collection, please contact [email protected]