1,645 research outputs found
The Impact of Judicial Reform on the Minnesota Supreme Court
On November 2, 1982, a majority of Minnesota voters approved a constitutional amendment that transformed the state\u27s appellate judiciary. A newly created Court of Appeals, currently consisting of 12 judges, began accepting cases on August 1, 1983, and deciding them on November 1, 1983. To assess the consequences of this change, ·the authors explored the rationale underlying the amendment, examined the anticipated costs and benefits of implementation, and analyzed case load data. Questionnaire responses from members of the Supreme Court are discussed, jurisdictional relationships between the two courts are explained, and decision· making practices are compared (including oral argument and published opinion frequency in cases raising constitutional questions). Prospects for enhancing the quality and reducing the quantity of decisions by the Supreme Court are good due to: 1) the diversion of nearly 80% of new filings since August 1983 to the Court of Appeals; and 2) the rapidity with which the Court of Appeals, sitting in panels of three, has been clearing its docket. The full impact of the reform had not yet been felt in Supreme Court chambers by February 1985. The time lag was due to the priority the high court was giving to disposition of a 1200-case backlog
Oscillations of a solid sphere falling through a wormlike micellar fluid
We present an experimental study of the motion of a solid sphere falling
through a wormlike micellar fluid. While smaller or lighter spheres quickly
reach a terminal velocity, larger or heavier spheres are found to oscillate in
the direction of their falling motion. The onset of this instability correlates
with a critical value of the velocity gradient scale
s. We relate this condition to the known complex rheology of wormlike
micellar fluids, and suggest that the unsteady motion of the sphere is caused
by the formation and breaking of flow-induced structures.Comment: 4 pages, 4 figure
24-Month Overall Survival from KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin with or without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous Non–Small Cell Lung Cancer
Introduction
Cohort G of KEYNOTE-021 (NCT02039674) evaluated the efficacy and safety of pembrolizumab plus pemetrexed-carboplatin (PC) versus PC alone as first-line therapy for advanced nonsquamous NSCLC. At the primary analysis (median follow-up time 10.6 months), pembrolizumab significantly improved objective response rate (ORR) and progression-free survival (PFS); the hazard ratio (HR) for overall survival (OS) was 0.90 (95% confidence interval [CI]: 0.42‒1.91). Herein, we present an updated analysis.
Methods
A total of 123 patients with previously untreated stage IIIB/IV nonsquamous NSCLC without EGFR and/or ALK receptor tyrosine kinase gene (ALK) aberrations were randomized 1:1 to four cycles of PC with or without pembrolizumab, 200 mg every 3 weeks. Pembrolizumab treatment continued for 2 years; maintenance pemetrexed was permitted in both groups. Eligible patients in the PC-alone group with radiologic progression could cross over to pembrolizumab monotherapy. p Values are nominal (one-sided p < 0.025).
Results
As of December 1, 2017, the median follow-up time was 23.9 months. The ORR was 56.7% with pembrolizumab plus PC versus 30.2% with PC alone (estimated difference 26.4% [95% CI: 8.9%‒42.4%, p = 0.0016]). PFS was significantly improved with pembrolizumab plus PC versus PC alone (HR = 0.53, 95% CI: 0.33‒0.86, p = 0.0049). A total of 41 patients in the PC-alone group received subsequent anti‒programmed death 1/anti‒programmed death ligand 1 therapy. The HR for OS was 0.56 (95% CI: 0.32‒0.95, p = 0.0151). Forty-one percent of patients in the pembrolizumab plus PC group and 27% in the PC-alone group had grade 3 to 5 treatment-related adverse events.
Conclusions
The significant improvements in PFS and ORR with pembrolizumab plus PC versus PC alone observed in the primary analysis were maintained, and the HR for OS with a 24-month median follow-up was 0.56, favoring pembrolizumab plus PC
Insights into the cultured bacterial fraction of corals
Bacteria associated with coral hosts are diverse and abundant, with recent studies suggesting involvement of these symbionts in host resilience to anthropogenic stress. Despite their putative importance, the work dedicated to culturing coral-associated bacteria has received little attention. Combining published and unpublished data, here we report a comprehensive overview of the diversity and function of culturable bacteria isolated from corals originating from tropical, temperate, and cold-water habitats. A total of 3,055 isolates from 52 studies were considered by our metasurvey. Of these, 1,045 had full-length 16S rRNA gene sequences, spanning 138 formally described and 12 putatively novel bacterial genera across the Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria phyla. We performed comparative genomic analysis using the available genomes of 74 strains and identified potential signatures of beneficial bacterium-coral symbioses among the strains. Our analysis revealed \u3e 400 biosynthetic gene clusters that underlie the biosynthesis of antioxidant, antimicrobial, cytotoxic, and other secondary metabolites. Moreover, we uncovered genomic features-not previously described for coral-bacterium symbioses-potentially involved in host colonization and host-symbiont recognition, antiviral defense mechanisms, and/or integrated metabolic interactions, which we suggest as novel targets for the screening of coral probiotics. Our results highlight the importance of bacterial cultures to elucidate coral holobiont functioning and guide the selection of probiotic candidates to promote coral resilience and improve holistic and customized reef restoration and rehabilitation efforts
Role of the Transcriptional Corepressor Bcor in Embryonic Stem Cell Differentiation and Early Embryonic Development
Bcor (BCL6 corepressor) is a widely expressed gene that is mutated in patients with X-linked Oculofaciocardiodental (OFCD) syndrome. BCOR regulates gene expression in association with a complex of proteins capable of epigenetic modification of chromatin. These include Polycomb group (PcG) proteins, Skp-Cullin-F-box (SCF) ubiquitin ligase components and a Jumonji C (Jmjc) domain containing histone demethylase. To model OFCD in mice and dissect the role of Bcor in development we have characterized two loss of function Bcor alleles. We find that Bcor loss of function results in a strong parent-of-origin effect, most likely indicating a requirement for Bcor in extraembryonic development. Using Bcor loss of function embryonic stem (ES) cells and in vitro differentiation assays, we demonstrate that Bcor plays a role in the regulation of gene expression very early in the differentiation of ES cells into ectoderm, mesoderm and downstream hematopoietic lineages. Normal expression of affected genes (Oct3/4, Nanog, Fgf5, Bmp4, Brachyury and Flk1) is restored upon re-expression of Bcor. Consistent with these ES cell results, chimeric animals generated with the same loss of function Bcor alleles show a low contribution to B and T cells and erythrocytes and have kinked and shortened tails, consistent with reduced Brachyury expression. Together these results suggest that Bcor plays a role in differentiation of multiple tissue lineages during early embryonic development
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International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.
The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations
Power poses – where do we stand?
<p>Dynamic results for Scenario 2.</p
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