Propensity score weighting is sensitive to model misspecification and outlying weights that can unduly influence results. The authors investigated whether trimming large weights downward can improve ...the performance of propensity score weighting and whether the benefits of trimming differ by propensity score estimation method. In a simulation study, the authors examined the performance of weight trimming following logistic regression, classification and regression trees (CART), boosted CART, and random forests to estimate propensity score weights. Results indicate that although misspecified logistic regression propensity score models yield increased bias and standard errors, weight trimming following logistic regression can improve the accuracy and precision of final parameter estimates. In contrast, weight trimming did not improve the performance of boosted CART and random forests. The performance of boosted CART and random forests without weight trimming was similar to the best performance obtainable by weight trimmed logistic regression estimated propensity scores. While trimming may be used to optimize propensity score weights estimated using logistic regression, the optimal level of trimming is difficult to determine. These results indicate that although trimming can improve inferences in some settings, in order to consistently improve the performance of propensity score weighting, analysts should focus on the procedures leading to the generation of weights (i.e., proper specification of the propensity score model) rather than relying on ad-hoc methods such as weight trimming.
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with lifelong impacts. Genetic and environmental factors contribute to ASD etiology, which remains incompletely understood. ...Research on ASD epidemiology has made significant advances in the past decade. Current prevalence is estimated to be at least 1.5% in developed countries, with recent increases primarily among those without comorbid intellectual disability. Genetic studies have identified a number of rare de novo mutations
and gained footing in the areas of polygenic risk, epigenetics, and gene-by-environment interaction. Epidemiologic investigations focused on nongenetic factors have established advanced parental age and preterm birth as ASD risk factors, indicated that prenatal exposure to air pollution and short interpregnancy interval are potential risk factors, and suggested the need for further exploration of certain prenatal nutrients, metabolic conditions, and exposure to endocrine-disrupting chemicals. We discuss future challenges and goals for ASD epidemiology as well as public health implications.
Variations in continental volcanic arc emissions have the potential to control atmospheric carbon dioxide (CO₂) levels and climate change on multimillion-year time scales. Here we present a ...compilation of ~120,000 detrital zircon uranium-lead (U-Pb) ages from global sedimentary deposits as a proxy to track the spatial distribution of continental magmatic arc systems from the Cryogenian period to the present. These data demonstrate a direct relationship between global arc activity and major climate shifts: Widespread continental arcs correspond with prominent early Paleozoic and Mesozoic greenhouse climates, whereas reduced continental arc activity corresponds with icehouse climates of the Cryogenian, Late Ordovician, late Paleozoic, and Cenozoic. This persistent coupled behavior provides evidence that continental volcanic outgassing drove long-term shifts in atmospheric CO₂ levels over the past ~720 million years.
Abstract Objective Examining covariate balance is the prescribed method for determining the degree to which propensity score methods should be successful at reducing bias. This study assessed the ...performance of various balance measures, including a proposed balance measure based on the prognostic score (similar to a disease risk score), to determine which balance measures best correlate with bias in the treatment effect estimate. Study Design and Setting The correlations of multiple common balance measures with bias in the treatment effect estimate produced by weighting by the odds, subclassification on the propensity score, and full matching on the propensity score were calculated. Simulated data were used, based on realistic data settings. Settings included both continuous and binary covariates and continuous covariates only. Results The absolute standardized mean difference (ASMD) in prognostic scores, the mean ASMD (in covariates), and the mean t -statistic all had high correlations with bias in the effect estimate. Overall, prognostic scores displayed the highest correlations with bias of all the balance measures considered. Prognostic score measure performance was generally not affected by model misspecification, and the prognostic score measure performed well under a variety of scenarios. Conclusion Researchers should consider using prognostic score–based balance measures for assessing the performance of propensity score methods for reducing bias in nonexperimental studies.
Introduction
The impact of liver cirrhosis on the difficulty of minimal invasive liver resection (MILR) remains controversial and current difficulty scoring systems do not take in to account the ...presence of cirrhosis as a significant factor in determining the difficulty of MILR. We hypothesized that the difficulty of MILR is affected by the presence of cirrhosis. Hence, we performed a 1:1 matched-controlled study comparing the outcomes between patients undergoing MILR with and without cirrhosis including the Iwate system and Institut Mutualiste Montsouris (IMM) system in the matching process.
Methods
Between 2006 and 2019, 598 consecutive patients underwent MILR of which 536 met the study inclusion criteria. There were 148 patients with cirrhosis and 388 non-cirrhotics. One-to-one coarsened exact matching identified approximately exact matches between 100 cirrhotic patients and 100 non-cirrhotic patients.
Results
Comparison between MILR patients with cirrhosis and non-cirrhosis in the entire cohort demonstrated that patients with cirrhosis were associated with a significantly increased open conversion rate, transfusion rate, need for Pringles maneuver, postoperative, stay, postoperative morbidity and postoperative 90-day mortality. After 1:1 coarsened exact matching, MILR with cirrhosis were significantly associated with an increased open conversion rate (15% vs 6%,
p
= 0.03), operation time (261 vs 238 min,
p
< 0.001), blood loss (607 vs 314 mls,
p
= 0.002), transfusion rate (22% vs 9%,
p
= 0.001), need for application of Pringles maneuver (51% vs 34%,
p
= 0.010), postoperative stay (6 vs 4.5 days,
p
= 0.004) and postoperative morbidity (26% vs 13%,
p
= 0.029).
Conclusion
The presence of liver cirrhosis affected both the intraoperative technical difficulty and postoperative outcomes of MILR and hence should be considered an important parameter to be included in future difficulty scoring systems for MILR.
In a record-linkage study in Stockholm, Sweden, the year 2011 prevalence of diagnosed autism spectrum disorders (ASD) was found to be 0.40, 1.74, 2.46, and 1.76 % among 0–5, 6–12, 13–17, and ...18–27 year olds, respectively. The corresponding proportion of cases with a recorded diagnosis of intellectual disability was 17.4, 22.1, 26.1 and 29.4 %. Between 2001 and 2011, ASD prevalence increased almost 3.5 fold among children aged 2–17 years. The increase was mainly accounted for by an eightfold increase of ASD without intellectual disability (from 0.14 to 1.10 %), while the prevalence of ASD with intellectual disability increased only slightly (from 0.28 to 0.34 %). The increase in ASD prevalence is likely contributed to by extrinsic factors such as increased awareness and diagnostics.
Hepatocellular carcinoma (HCC) is the fifth most common cancer with high mortality, due to late diagnosis and limited treatment options. Blood miRNAs, which circulate in a highly stable, cell-free ...form, show promise as novel potential biomarkers for early detection of HCC. Whole miRNome profiling was performed to identify deregulated miRNAs between HCC and normal healthy (NH) volunteers. These deregulated miRNAs were validated in an independent cohort of HCC, NH and chronic Hepatitis B (CHB) volunteers and finally in a 3
cohort comprising NH, CHB, cirrhotic and HCC volunteers to evaluate miRNA changes during disease progression. The associations between circulating miRNAs and liver-damage markers, clinicopathological characteristics and survival outcomes were analysed to identify prognostic markers. Twelve miRNAs are differentially expressed between HCC and NH individuals in all three cohorts. Five upregulated miRNAs (miR-122-5p, miR-125b-5p, miR-885-5p, miR-100-5p and miR-148a-3p) in CHB, cirrhosis and HCC patients are potential biomarkers for CHB infection, while miR-34a-5p can be a biomarker for cirrhosis. Notably, four miRNAs (miR-1972, miR-193a-5p, miR-214-3p and miR-365a-3p) can distinguish HCC from other non-HCC individuals. Six miRNAs are potential prognostic markers for overall survival.
Epigenetic mechanisms, including histone post-translational modifications, control longevity in diverse organisms. Relatedly, loss of proper transcriptional regulation on a global scale is an ...emerging phenomenon of shortened life span, but the specific mechanisms linking these observations remain to be uncovered. Here, we describe a life span screen in Saccharomyces cerevisiae that is designed to identify amino acid residues of histones that regulate yeast replicative aging. Our results reveal that lack of sustained histone H3K36 methylation is commensurate with increased cryptic transcription in a subset of genes in old cells and with shorter life span. In contrast, deletion of the K36me2/3 demethylase Rph1 increases H3K36me3 within these genes, suppresses cryptic transcript initiation, and extends life span. We show that this aging phenomenon is conserved, as cryptic transcription also increases in old worms. We propose that epigenetic misregulation in aging cells leads to loss of transcriptional precision that is detrimental to life span, and, importantly, this acceleration in aging can be reversed by restoring transcriptional fidelity.
Transcatheter aortic valve replacement (TAVR) is being increasingly performed in patients with bicuspid aortic valve stenosis (AS).
This study sought to compare the procedural and clinical outcomes ...in patients with bicuspid versus tricuspid AS from the Bicuspid AS TAVR multicenter registry.
Outcomes of 561 patients with bicuspid AS and 4,546 patients with tricuspid AS were compared after propensity score matching, assembling 546 pairs of patients with similar baseline characteristics. Procedural and clinical outcomes were recorded according to Valve Academic Research Consortium-2 criteria.
Compared with patients with tricuspid AS, patients with bicuspid AS had more frequent conversion to surgery (2.0% vs. 0.2%; p = 0.006) and a significantly lower device success rate (85.3% vs. 91.4%; p = 0.002). Early-generation devices were implanted in 320 patients with bicuspid and 321 patients with tricuspid AS, whereas new-generation devices were implanted in 226 and 225 patients with bicuspid and tricuspid AS, respectively. Within the group receiving early-generation devices, bicuspid AS had more frequent aortic root injury (4.5% vs. 0.0%; p = 0.015) when receiving the balloon-expanding device, and moderate-to-severe paravalvular leak (19.4% vs. 10.5%; p = 0.02) when receiving the self-expanding device. Among patients with new-generation devices, however, procedural results were comparable across different prostheses. The cumulative all-cause mortality rates at 2 years were comparable between bicuspid and tricuspid AS (17.2% vs. 19.4%; p = 0.28).
Compared with tricuspid AS, TAVR in bicuspid AS was associated with a similar prognosis, but lower device success rate. Procedural differences were observed in patients treated with the early-generation devices, whereas no differences were observed with the new-generation devices.
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