Influence of the megathrust earthquake cycle on upper-plate deformation in the Cascadia forearc of Washington State, USA

The influence of subduction zone earthquake cycle processes on permanent forearc deformation is poorly understood. In the Cascadia subduction zone forearc of Washington State, USA, deformed and incised fluvial terraces serve as archives of longer-term (103–104 yr) strain manifest as both fluvial incision and slip on upper-plate faults. We focus on comparing these geomorphic records in the Wynoochee River valley in the southern Olympic Mountains with short-term (101 yr) deformation driven by interseismic subduction zone coupling. We use optically stimulated luminescence dating and high-resolution elevation data to characterize strath terrace incision and differential uplift across the Canyon River fault, which cuts Wynoochee River terraces. This analysis demonstrates reverse slip rates of ∼0.1–0.3 mm/yr over the past ∼12–37 k.y., which agree with rates predicted by a GPS-constrained boundary element model of interseismic stress from Cascadia subduction zone coupling. Similarly, model-predicted patterns of interseismic uplift mimic the overall pattern of incision in the lower Wynoochee River valley, as revealed by strath elevations dated at 14.1 ± 1.2 ka. Agreement between modeled short-term and observed long-term records of forearc strain suggests that interseismic stress drives slip on upper-plate faults and fluvial incision in Cascadia. Consistency over multiple time scales may indicate relative stability in spatial patterns of subduction zone coupling over at least ∼104 yr intervals

Association of a Frailty Screening Initiative With Postoperative Survival at 30, 180, and 365 Days

IMPORTANCE As the US population ages, the number of operations performed on elderly patients will likely increase. Frailty predicts postoperative mortality and morbidity more than age alone, thus presenting opportunities to identify the highest-risk surgical patients and improve their outcomes. OBJECTIVE To examine the effect of the Frailty Screening Initiative (FSI) on mortality and complications by comparing the surgical outcomes of a cohort of surgical patients treated before and after implementation of the FSI. DESIGN, SETTING, AND PARTICIPANTS This single-site, facility-wide, prospective cohort quality improvement project studied all 9153 patients from a level 1b Veterans Affairs medical center who presented for major, elective, noncardiac surgery from October 1, 2007, to July 1, 2014. INTERVENTIONS Assessment of preoperative frailty in all patients scheduled for elective surgery began in July 2011. Frailty was assessed with the Risk Analysis Index (RAI), and the records of all frail patients (RAI score,≥ 21) were flagged for administrative review by the chief of surgery (or designee) before the scheduled operation. On the basis of this review, clinicians from surgery, anesthesia, critical care, and palliative care were notified of the patient’s frailty and associated surgical risks; if indicated, perioperative plans were modified based on team input. MAIN OUTCOMES AND MEASURES Postoperative mortality at 30, 180, and 365 days. RESULTS From October 1, 2007, to July 1, 2014, a total of 9153 patients underwent surgery (mean [SD] age, 60.3 [13.5] years; female, 653 [7.1%]; and white, 7096 [79.8%]). Overall 30-day mortality decreased from 1.6%(84 of 5275 patients) to 0.7%(26 of 3878 patients, P \u3c .001) after FSI implementation. Improvement was greatest among frail patients (12.2% [24 of 197 patients] to 3.8% [16 of 424 patients], P \u3c .001), although mortality rates also decreased among the robust patients (1.2% [60 of 5078 patients] to 0.3% [10 of 3454 patients], P \u3c .001). The magnitude of improvement among frail patients increased at 180 (23.9% [47 of 197 patients] to 7.7% [30 of 389 patients], P \u3c .001) and 365 days (34.5% [68 of 197 patients] to 11.7% [36 of 309 patients], P \u3c .001). Multivariable models revealed improved survival after FSI implementation, controlling for age, frailty, and predicted mortality (adjusted odds ratio for 180-day survival, 2.87; 95% CI, 1.98-4.16). CONCLUSIONS AND RELEVANCE Implementation of the FSI was associated with reduced mortality, suggesting the feasibility of widespread screening of patients preoperatively to identify frailty and the efficacy of system-level initiatives aimed at improving their surgical outcomes. Additional investigation is required to establish a causal connection

Improving the development, monitoring and reporting of stroke rehabilitation research: consensus-based core recommendations from the Stroke Recovery and Rehabilitation Roundtable (SRRR)

Recent reviews have demonstrated that the quality of stroke rehabilitation research has continued to improve over the last four decades but despite this progress there are still many barriers in moving the field forward. Rigorous development, monitoring and complete reporting of interventions in stroke trials are essential in providing rehabilitation evidence that is robust, meaningful and implementable. An international partnership of stroke rehabilitation experts committed to develop consensus-based core recommendations with a remit of addressing the issues identified as limiting stroke rehabilitation research in the areas of developing, monitoring and reporting stroke rehabilitation interventions. Work exploring each of the three areas took place via multiple teleconferences and a two-day meeting in Philadelphia in May 2016. A total of 15 recommendations were made. To validate the need for the recommendations the group reviewed all stroke rehabilitation trials published in 2015 (n=182 papers). Our review highlighted that the majority of publications did not clearly describe how interventions were developed or monitored during the trial. In particular, under-reporting of the theoretical rationale for the intervention and the components of the intervention calls into question many interventions that have been evaluated for efficacy. More trials were found to have addressed the reporting of interventions recommendations than those related to development or monitoring. Nonetheless the majority of reporting recommendations were still not adequately described. To progress the field of stroke rehabilitation research and to ensure stroke patients receive optimal evidence based clinical care we urge the research community to endorse and adopt our recommendations

Insights into the Musa genome: Syntenic relationships to rice and between Musa species

<p>Abstract</p> <p>Background</p> <p><it>Musa </it>species (Zingiberaceae, Zingiberales) including bananas and plantains are collectively the fourth most important crop in developing countries. Knowledge concerning <it>Musa </it>genome structure and the origin of distinct cultivars has greatly increased over the last few years. Until now, however, no large-scale analyses of <it>Musa </it>genomic sequence have been conducted. This study compares genomic sequence in two <it>Musa </it>species with orthologous regions in the rice genome.</p> <p>Results</p> <p>We produced 1.4 Mb of <it>Musa </it>sequence from 13 BAC clones, annotated and analyzed them along with 4 previously sequenced BACs. The 443 predicted genes revealed that Zingiberales genes share GC content and distribution characteristics with eudicot and Poaceae genomes. Comparison with rice revealed microsynteny regions that have persisted since the divergence of the Commelinid orders Poales and Zingiberales at least 117 Mya. The previously hypothesized large-scale duplication event in the common ancestor of major cereal lineages within the Poaceae was verified. The divergence time distributions for <it>Musa</it>-Zingiber (Zingiberaceae, Zingiberales) orthologs and paralogs provide strong evidence for a large-scale duplication event in the <it>Musa </it>lineage after its divergence from the Zingiberaceae approximately 61 Mya. Comparisons of genomic regions from <it>M. acuminata </it>and <it>M. balbisiana </it>revealed highly conserved genome structure, and indicated that these genomes diverged circa 4.6 Mya.</p> <p>Conclusion</p> <p>These results point to the utility of comparative analyses between distantly-related monocot species such as rice and <it>Musa </it>for improving our understanding of monocot genome evolution. Sequencing the genome of <it>M. acuminata </it>would provide a strong foundation for comparative genomics in the monocots. In addition a genome sequence would aid genomic and genetic analyses of cultivated <it>Musa </it>polyploid genotypes in research aimed at localizing and cloning genes controlling important agronomic traits for breeding purposes.</p

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Bush the transnationalist: a reappraisal of the unilateralist impulse in US foreign policy, 2001-2009

This article challenges the common characterisation of George W. Bush’s foreign policy as “unilateral.” It argues that the Bush administration developed a new post-9/11 understanding of terrorism as a transnational, networked phenomenon shaped by the forces of globalisation. This led to a new strategic emphasis on bi- and multilateral security co-operation and counterterrorism operations, especially outside of Afghanistan and Iraq, driven by the perceived need to counter a transnational security challenge present in multiple locations. This (flawed) attempt to engage with transnational security challenges supplemented the existing internationalist pillar of the Bush administration’s foreign policy. Highlighting the transnational realm of international relations and the ways in which the Bush administration was able to co-opt other states to tackle perceived transnational challenges also shows the high importance the administration attached to concerted action even as it frequented eschewed institutional multilateralism

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