GISS‐E2.1: Configurations and Climatology Kelley, Maxwell; Schmidt, Gavin A; Nazarenko, Larissa ...
Journal of advances in modeling earth systems,
August 2020, Volume:
12, Issue:
8
Journal Article
Peer reviewed
Open access
This paper describes the GISS‐E2.1 contribution to the Coupled Model Intercomparison Project, Phase 6 (CMIP6). This model version differs from the predecessor model (GISS‐E2) chiefly due to ...parameterization improvements to the atmospheric and ocean model components, while keeping atmospheric resolution the same. Model skill when compared to modern era climatologies is significantly higher than in previous versions. Additionally, updates in forcings have a material impact on the results. In particular, there have been specific improvements in representations of modes of variability (such as the Madden‐Julian Oscillation and other modes in the Pacific) and significant improvements in the simulation of the climate of the Southern Oceans, including sea ice. The effective climate sensitivity to 2xCO2 is slightly higher than previously at 2.7‐‐3.1°C (depending on version), and is a result of lower CO2 radiative forcing and stronger positive feedbacks.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
One year of durvalumab following concurrent chemoradiotherapy improves progression-free (PFS) and overall survival (OS) for patients with stage III non-small cell lung cancer (NSCLC). However, the ...real-world efficacy of durvalumab has not been determined. We conducted a multi-center observational cohort study across the Veterans Health Administration, including patients with stage III NSCLC who received concurrent chemoradiotherapy and durvalumab, compared to patients who received concurrent chemoradiotherapy alone. Kaplan-Meier and Cox regression approaches were used to identify factors associated with PFS and OS. We calculated a hazard ratio and efficacy-effectiveness factor to compare OS of veterans to the referenced clinical trial population. A total of 1006 patients with stage III NSCLC who received concurrent chemoradiotherapy and at least one dose of durvalumab from November 2017 to April 2021 were compared to 989 patients who received concurrent chemoradiotherapy alone from January 2015 to December 2016. Adjuvant durvalumab was associated with higher PFS (HR 0.62, 95% CI 0.55-0.70,
< 0.001) and OS (HR 0.57, 95% CI 0.50-0.66,
< 0.001). OS was shorter in veterans compared to PACIFIC (HR 1.24, 95% CI 1.03-1.48,
= 0.02: EE gap 0.73). OS of veterans with stage III NSCLC treated with adjuvant durvalumab is improved compared to a modern comparator but is reduced compared to the PACIFIC population.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
We conducted a randomized field trial to test an academic vocabulary intervention designed to bolster the language and literacy skills of linguistically diverse sixth-grade students (N = 2,082; n = ...1,469 from a home where English is not the primary language), many demonstrating low achievement, enrolled in 14 urban middle schools. The 20-week classroom-based intervention improved students' vocabulary knowledge, morphological awareness skills, and comprehension of expository texts that included academic words taught, as well as their performance on a standardized measure of written language skills. The effects were generally larger for students whose primary home language is not English and for those students who began the intervention with underdeveloped vocabulary knowledge.
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BFBNIB, NMLJ, NUK, OILJ, PNG, SAZU, UKNU, UL, UM, UPUK
We performed a comprehensive assessment of rare inherited variation in autism spectrum disorder (ASD) by analyzing whole-genome sequences of 2,308 individuals from families with multiple affected ...children. We implicate 69 genes in ASD risk, including 24 passing genome-wide Bonferroni correction and 16 new ASD risk genes, most supported by rare inherited variants, a substantial extension of previous findings. Biological pathways enriched for genes harboring inherited variants represent cytoskeletal organization and ion transport, which are distinct from pathways implicated in previous studies. Nevertheless, the de novo and inherited genes contribute to a common protein-protein interaction network. We also identified structural variants (SVs) affecting non-coding regions, implicating recurrent deletions in the promoters of DLG2 and NR3C2. Loss of nr3c2 function in zebrafish disrupts sleep and social function, overlapping with human ASD-related phenotypes. These data support the utility of studying multiplex families in ASD and are available through the Hartwell Autism Research and Technology portal.
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•Identification of rare inherited variants associated with ASD and 16 new ASD risk genes•Inherited risk reveals both new biological pathways and shared PPI with known genes•We develop and validate a machine learning algorithm (ARC) to remove WGS artifacts•NR3C2 mutations define a novel syndromic form of ASD, which we model in zebrafish
Whole-genome sequencing from families with multiple ASD-affected children allows identification of rare inherited variants associated with disease and definition of a syndromic form of disease caused by mutations in NR3C2.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The treatment of mitral valve disease in the presence of mitral annular calcification (MAC) is associated with an increased risk of cardiovascular and all-cause mortality. Various surgical and ...transcatheter techniques for the treatment of mitral disease with severe MAC have been described. However, these procedures are associated with high risk of operative morbidity and mortality. We describe our experience with open surgical implantation of a balloon-expandable valve (BEV) in patients with severe MAC as an alternative approach.
BEV implantation was performed with direct vision through the left atrium via a median sternotomy or minimally invasive approach. The midportion of the anterior leaflet is excised, and a ventricular septal myectomy performed if there is high risk for left ventricular outflow tract obstruction. The primary outcome was technical success according to the Mitral Valve Academic Research Consortium criteria; secondary outcomes were 30-day and 1-year mortality.
From October 2015 through October 2020, 51 patients at 2 institutions underwent BEV-in-MAC (mean age, 73.9 ± 8.8 years; 60.8% 31/51 were female; mean Society of Thoracic Surgeons predicted risk of mortality: 6.8% ± 4.8%). Technical success was 94.1% (48/51). Thirty-day and 1-year mortality were 13.7% (7/51) and 33.3% (15/45), and for stroke 3.9% (2/51) and 4.4% (2/45), respectively.
Surgical implantation of a BEV in the mitral position offers a treatment option for patients with mitral valve disease complicated by severe MAC who are at increased risk for conventional surgical approaches and at risk for left ventricular outflow tract obstruction with transcatheter approaches.
Summary of study findings of balloon-expandable valve (BEV) implantation in 51 patients with mitral valve disease complicated by annular calcification (MAC) who were at increased risk for conventional surgical or transcatheter approaches. Display omitted
One of the hypotheses that may help explain the loss of honey bee colonies worldwide is the increasing potential for exposure of honey bees to complex mixtures of pesticides. To better understand ...this phenomenon, two multi-residue methods based on different extraction and cleanup procedures have been developed, and compared for the determination of 11 relevant pesticides in honey bees, pollen, and wax by gas chromatography–quadrupole mass spectrometry. Sample preparatory methods included solvent extraction followed by gel permeation chromatography (GPC) cleanup and cleanup using a dispersive solid-phase extraction with zirconium-based sorbents (Z-Sep). Matrix effects, method detection limits, recoveries, and reproducibility were evaluated and compared. Method detection limits (MDL) of the pesticides for the GPC method in honey bees, pollen, and wax ranged from 0.65 to 5.92ng/g dw, 0.56 to 6.61ng/g dw, and 0.40 to 8.30ng/g dw, respectively, while MDLs for the Z-Sep method were from 0.33 to 4.47ng/g dw, 0.42 to 5.37ng/g dw, and 0.51 to 5.34ng/g dw, respectively. The mean recoveries in all matrices and at three spiking concentrations ranged from 64.4% to 149.5% and 71.9% to 126.2% for the GPC and Z-Sep methods, with relative standard deviation between 1.5–25.3% and 1.3–15.9%, respectively. The results showed that the Z-Sep method was more suitable for the determination of the target pesticides, especially chlorothalonil, in bee hive samples. The Z-Sep method was then validated using a series of field-collected bee hive samples taken from honey bee colonies in Virginia.
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•Pesticide exposure has been linked with honey bee population losses.•Reliable multi-residue analytical methods are needed for trace pesticide analysis.•Two sample preparation methods were tested: GPC and d-SPE with Z-Sep.•Z-Sep cleanup was the preferred method and was successful with field-collected media.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The objective of this study was to discover clinical and pharmacogenetic factors associated with bevacizumab-related gastrointestinal hemorrhage in Cancer and Leukemia Group B (Alliance) 90401. ...Patients with metastatic castration-resistant prostate cancer received docetaxel and prednisone ± bevacizumab. Patients were genotyped using Illumina HumanHap610-Quad and assessed using cause-specific risk for association between single nucleotide polymorphisms (SNPs) and gastrointestinal hemorrhage. In 1008 patients, grade 2 or higher gastrointestinal hemorrhage occurred in 9.5% and 3.8% of bevacizumab (n = 503) and placebo (n = 505) treated patients, respectively. Bevacizumab (P < 0.001) and age (P = 0.002) were associated with gastrointestinal hemorrhage. In 616 genetically estimated Europeans (n = 314 bevacizumab and n = 302 placebo treated patients), grade 2 or higher gastrointestinal hemorrhage occurred in 9.6% and 2.0% of patients, respectively. One SNP (rs1478947; HR 6.26; 95% CI 3.19-12.28; P = 9.40 × 10
) surpassed Bonferroni-corrected significance. Grade 2 or higher gastrointestinal hemorrhage rate was 33.3% and 6.2% in bevacizumab-treated patients with the AA/AG and GG genotypes, versus 2.9% and 1.9% in the placebo arm, respectively. Prospective validation of these findings and functional analyses are needed to better understand the genetic contribution to treatment-related gastrointestinal hemorrhage.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
One year of adjuvant durvalumab following concurrent chemoradiotherapy significantly improves progression-free survival (PFS) and overall survival (OS) for patients with stage III non-small cell lung ...cancer (NSCLC). However, the optimal length of adjuvant therapy has not been determined.
We identified patients with stage III NSCLC treated with definitive chemoradiation and adjuvant durvalumab from November 2017 to April 2021 from the United States Veterans Affairs system. Predictors of early durvalumab discontinuation were evaluated with Cox proportional hazards regression. The effect of differing durations of durvalumab treatment (up to 6, 9, and 12 months) on PFS and OS were compared with a marginal structural model and time-dependent Cox modelling.
We included 1006 patients with stage III non-small cell lung cancer who received concurrent chemoradiotherapy and at least one dose of adjuvant durvalumab. The median duration of durvalumab treatment was 7 months (interquartile range 2.8–11.5) and 31% completed the intended durvalumab course. The most common reasons for early discontinuation were tumour progression (22%), immune-related adverse events (15%), and non-immune-related toxicity (6.0%), Marginal structural models suggested similar PFS for 9 months versus 12 months of durvalumab treatment and inferior PFS for 6 months versus 12 months.
A substantial proportion of patients undergoing adjuvant durvalumab discontinue therapy early due to toxicity, and shorter durvalumab treatment durations may provide similar disease control to 12 months of therapy. Prospective randomised controlled studies are needed to characterise the optimal durvalumab treatment duration in locally advanced NSCLC patients.
•Real-world patients have higher durvalumab toxicity than in clinical trials.•Real-world patients receive fewer durvalumab cycles than in clinical trials.•Shorter adjuvant durvalumab durations may be equivalent to the current standard.•Shorter durvalumab durations may decrease cost and improve toxicity.•Prospective study of shorter durvalumab durations is warranted.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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