Category: Statistics

Biom J. 2021 Jul 28. doi: 10.1002/bimj.202000256. Online ahead of print.

ABSTRACT

Chromatin dynamics are central to the regulation of gene expression and genome stability. In order to improve understanding of the factors regulating chromatin dynamics, the genes encoding these factors are deleted and the differential gene expression profiles are determined using approaches such as RNA sequencing. Here, we analyzed a gene expression dataset aimed at uncovering the function of the relatively uncharacterized chromatin regulator, Set4, in the model system Saccharomyces cerevisiae (budding yeast). The main theme of this paper focuses on identifying the highly differentially expressed genes in cells deleted for Set4 (referred to as Set4 Δ mutant dataset) compared to the wild-type yeast cells. The Set4 Δ mutant data produce a spiky distribution on the log-fold changes of their expressions, and it is reasonably assumed that genes which are not highly differentially expressed come from a mixture of two normal distributions. We propose an adaptive local false discovery rate (FDR) procedure, which estimates the null distribution of the log-fold changes empirically. We numerically show that, unlike existing approaches, our proposed method controls FDR at the aimed level (0.05) and also has competitive power in finding differentially expressed genes. Finally, we apply our procedure to analyzing the Set4 Δ mutant dataset.

PMID:34320248 | DOI:10.1002/bimj.202000256

Hepatology. 2021 Jul 28. doi: 10.1002/hep.32074. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Wilson disease (WD) is an autosomal recessive disorder caused by ATP7B gene mutations leading to pathologic accumulation of copper in the liver and brain. Adoption of initial treatments for WD was based on empiric observations. These therapies are effective, but there are still are unmet needs for which new treatment modalities are being developed. Randomized controlled phase 3 studies are lacking for current WD treatments.

APPROACH AND RESULTS: The first Wilson Disease Aarhus Symposium (May 2019) included a workshop on randomized clinical trial (RCT) design. The authors of the paper were organizers or presented during this workshop and this article presents their consensus on the design of clinical trials for WD, addressing trial population, treatment comparators, inclusion and exclusion criteria and treatment endpoints. To achieve adequate recruitment of patients with this rare disorder, the study groups should include all clinical phenotypes and treatment-experienced as well as treatment-naive patients.

CONCLUSIONS: The primary study endpoint should be clinical or a composite endpoint until appropriate surrogate endpoints are validated. Standardization of clinical trials will permit pooling of data and allow for better treatment comparisons, as well as reduce the future numbers of patients needed per trial.

PMID:34320232 | DOI:10.1002/hep.32074

Mov Disord. 2021 Jul 28. doi: 10.1002/mds.28732. Online ahead of print.

ABSTRACT

BACKGROUND: Several monogenic causes for isolated dystonia have been identified, but they collectively account for only a small proportion of cases. Two genome-wide association studies have reported a few potential dystonia risk loci; but conclusions have been limited by small sample sizes, partial coverage of genetic variants, or poor reproducibility.

OBJECTIVE: To identify robust genetic variants and loci in a large multicenter cervical dystonia cohort using a genome-wide approach.

METHODS: We performed a genome-wide association study using cervical dystonia samples from the Dystonia Coalition. Logistic and linear regressions, including age, sex, and population structure as covariates, were employed to assess variant- and gene-based genetic associations with disease status and age at onset. We also performed a replication study for an identified genome-wide significant signal.

RESULTS: After quality control, 919 cervical dystonia patients compared with 1491 controls of European ancestry were included in the analyses. We identified one genome-wide significant variant (rs2219975, chromosome 3, upstream of COL8A1, P-value 3.04 × 10^-8 ). The association was not replicated in a newly genotyped sample of 473 cervical dystonia cases and 481 controls. Gene-based analysis identified DENND1A to be significantly associated with cervical dystonia (P-value 1.23 × 10^-6 ). One low-frequency variant was associated with lower age-at-onset (16.4 ± 2.9 years, P-value = 3.07 × 10^-8 , minor allele frequency = 0.01), located within the GABBR2 gene on chromosome 9 (rs147331823).

CONCLUSION: The genetic underpinnings of cervical dystonia are complex and likely consist of multiple distinct variants of small effect sizes. Larger sample sizes may be needed to provide sufficient statistical power to address the presumably multi-genic etiology of cervical dystonia. © 2021 International Parkinson and Movement Disorder Society.

PMID:34320236 | DOI:10.1002/mds.28732

J Gerontol B Psychol Sci Soc Sci. 2021 Jul 28:gbab141. doi: 10.1093/geronb/gbab141. Online ahead of print.

ABSTRACT

OBJECTIVE: To examine distributional effects of the 2008 recession and subsequent recovery across generational cohorts.

METHODS: Using data from the Survey of Consumer Finances (2007-2016), we constructed a measure of economic well-being accounting for income, household size and annuitized value of assets. We examine trajectories of adjusted income and inequality, using Gini coefficients and income shares by decile, for the overall population and by cohort during the recession and recovery.

RESULTS: Inequality declined temporarily during the recession, but reached new highs during the recovery. During recovery, population-level increases in economic resources were not reflected among below-median households, as the more concentrated financial assets rose while broader-based home equity and employment fell or remained stagnant. Inequality measures increased for cohorts in their primary working years (Generation-X and Baby Boomers), but not among the younger Millennials, who were at early stages of education, workforce entry and household formation.

DISCUSSION: The study illustrates an integrative approach to analyzing cumulative dis/advantage by considering interactions between historically consistent macro-level events, such as economic shocks or policy choices affecting all cohorts, and the persistent life-course processes that tend to increase heterogeneity and inequality as cohorts age over time. Although recovery policies led to rapid recovery of financial asset values, they did not proportionately reach those below the median or their economic resource-types. Results suggest that in a high-inequality environment, recovery policies from economic shocks may need tailoring to all levels of resources in order to achieve more equitable recovery outcomes and prevent exacerbating cohort inequality trajectories.

PMID:34320206 | DOI:10.1093/geronb/gbab141

Neurosurgery. 2021 Jul 28:nyab250. doi: 10.1093/neuros/nyab250. Online ahead of print.

ABSTRACT

BACKGROUND: Carotid endarterectomy (CEA) and carotid artery stenting (CAS) represent options to treat many patients with carotid stenosis. Although randomized trial data are plentiful, estimated rates of morbidity and mortality for both CEA and CAS have varied substantially.

OBJECTIVE: To evaluate rates of adverse outcomes after CAS and CEA in a large national database.

METHODS: We analyzed 84 191 adult patients undergoing elective, nonemergent CAS (n = 81 361) or CEA (n = 2830), from 2011 to 2018, in the American College of Surgeons’ National Surgical Quality Improvement Program database. Odds of adverse outcomes (30-d rates of stroke, myocardial infarction (MI), cardiac arrest, prolonged length of stay (LOS), readmission, reoperation, and mortality) were evaluated in propensity-matched (n = 2821) cohorts through logistic regression.

RESULTS: In the propensity-matched cohorts, CAS had increased odds of periprocedural stroke (odds ratio [OR] 1.97, 95% CI 1.32-2.95) and decreased odds of cardiac arrest (OR 0.33, 95% CI 0.13-0.84) and 30-d reoperation (OR 0.59, 95% CI 0.44-0.80) compared to CEA. Relative odds of MI, prolonged LOS, discharge to destination other than home, 30-d readmission, or 30-d mortality were statistically similar. In the unmatched patient population, rates of adverse outcomes with CEA were constant over time; however, for CAS, rates of stroke increased over time. In both the matched and unmatched patient cohorts, patients 70 yr and older had lower rates of post-procedural stroke with CEA, but not with CAS, compared to younger patients.

CONCLUSION: In a propensity-matched analysis of a large, prospectively collected, national, surgical database, CAS was associated with increased odds of periprocedural stroke, which increased over time. Rates of MI and death were not significantly different between the 2 procedures.

PMID:34320217 | DOI:10.1093/neuros/nyab250

J Natl Cancer Inst. 2021 Jul 28:djab147. doi: 10.1093/jnci/djab147. Online ahead of print.

ABSTRACT

BACKGROUND: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers.

METHODS: 483 BRCA1 and 1,318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were three versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen-receptor (ER) negative (PRSER-) or ER-positive (PRSER+) breast cancer risk.

RESULTS: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07-1.83) for BRCA1 and 1.33 (95% CI = 1.16-1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for both BRCA1 (OR = 1.73, 95% CI = 1.28-2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34-1.91) carriers. The estimated breast cancer ORs were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions.

CONCLUSIONS: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and to inform clinical management.

PMID:34320204 | DOI:10.1093/jnci/djab147

Nucleic Acids Res. 2021 Jul 28:gkab637. doi: 10.1093/nar/gkab637. Online ahead of print.

ABSTRACT

Whole genome bisulphite sequencing (WGBS) permits the genome-wide study of single molecule methylation patterns. One of the key goals of mammalian cell-type identity studies, in both normal differentiation and disease, is to locate differential methylation patterns across the genome. We discuss the most desirable characteristics for DML (differentially methylated locus) and DMR (differentially methylated region) detection tools in a genome-wide context and choose a set of statistical methods that fully or partially satisfy these considerations to compare for benchmarking. Our data simulation strategy is both biologically informed-employing distribution parameters derived from large-scale consortium datasets-and thorough. We report DML detection ability with respect to coverage, group methylation difference, sample size, variability and covariate size, both marginally and jointly, and exhaustively with respect to parameter combination. We also benchmark these methods on FDR control and computational time. We use this result to backend and introduce an expanded version of DMRcate: an existing DMR detection tool for microarray data that we have extended to now call DMRs from WGBS data. We compare DMRcate to a set of alternative DMR callers using a similarly realistic simulation strategy. We find DMRcate and RADmeth are the best predictors of DMRs, and conclusively find DMRcate the fastest.

PMID:34320181 | DOI:10.1093/nar/gkab637

Eur J Orthod. 2021 Jul 28:cjab048. doi: 10.1093/ejo/cjab048. Online ahead of print.

ABSTRACT

OBJECTIVES: This controlled study aimed to evaluate the effects of Herbst therapy on the trabecular structure of the condyle and angulus mandible using fractal dimension analysis (FD-A) accompanied by skeletal cephalometric changes.

MATERIAL AND METHOD: The panoramic and cephalometric radiographs of 30 patients with skeletal Class II malocclusion treated with the Herbst appliance (C II-H group, mean age: 15.23 ± 1.08), 30 patients with skeletal Class II malocclusion that received fixed orthodontic treatment (C II-C group, mean age: 15.73 ± 1.38), and 30 patients with skeletal Class I malocclusion (C I-C group, mean age: 15.90 ± 1.30) were selected. FD-A was performed on the superoposterior region (C-SP) and centre of the condyles (C-C) and the mandibular angulus (Ang) on the panoramic radiographs taken at the pretreatment (T0), intermediate stage of treatment (T1), and posttreatment (T2) timepoints just like cephalometric analysis.

RESULTS: Herbst therapy provided a statistically significant increase in SNB, ANS-Me, Na-Me, S-Go, Co-Gn and a decrease in ANB and overjet (P < 0.05). All skeletal changes remained stable during the fixed appliance treatment after Herbst. The FD values in C-C increased (P < 0.05), and C-SP values decreased (P < 0.05) during Herbst therapy, while after removal of the Herbst appliance, no significant change was observed despite an increase in C-SP. The Ang value did not change during Herbst treatment, but then increased significantly (P < 0.05). There was no significant change in the FD values of the C I-C and C II-C groups at any stage of treatment. The C-C and C-SP changes at T1-T0 period, C-SP and Ang changes at T2-T1 period, and C-C, C-SP, and Ang values at T2-T0 period were found higher in C II-H group compared with the C II-C group significantly (P < 0.05).

CONCLUSION: Herbst therapy changed the trabecular structure of the condyles in different directions at the superoposterior and central regions of the condyles, while the structural complexity of the angulus mandible, which did not change during the Herbst treatment, increased during the fixed orthodontic treatment after Herbst.

PMID:34320187 | DOI:10.1093/ejo/cjab048

Rev Bras Enferm. 2021 Jul 26;74(6):e20210061. doi: 10.1590/0034-7167-2021-0061. eCollection 2021.

ABSTRACT

OBJECTIVE: To analyze the factors associated with sex without the use of condoms in consumers of sexually explicit media (SEM).

METHODS: Cross-sectional study, with a sample of 172 participants selected and collected through social media. To assess the predictors of unprotected sexual practices, the Poisson regression model was used. Values were expressed as a robust prevalence ratio (PR) with their respective confidence intervals.

RESULTS: There was a statistically significant association between, the use of condoms and the type of scenes that the participants prefer (p = 0.03), the preference for films with scenes involving unprotected sex or even those that do not care about protection (p = 0.02), the type of pornography watched influencing sexual relations (p = 0.017), and the number of scenes seen per week (p = 0.05).

CONCLUSIONS: The lack of condom use was associated with the access to erotic scenes.

PMID:34320146 | DOI:10.1590/0034-7167-2021-0061

Rev Bras Enferm. 2021 Jul 26;74(6):e20210125. doi: 10.1590/0034-7167-2021-0125. eCollection 2021.

ABSTRACT

OBJECTIVE: To evaluate the impact of implementing the SafeCare clinical supervision model on nurses’ job satisfaction and emotional competence profile.

METHODS: This is a quasi-experimental study, with a sample of 28 nurses from a hospital in northern Portugal. A self-administered questionnaire was applied, used as pre and post-test, which included: sociodemographic and professional characterization; “Job Satisfaction Scale”; and “Veiga Emotional Competence Scale”. We conducted descriptive statistical analysis and the Wilcoxon Test.

RESULTS: A significant decrease in the nurses’ satisfaction with hierarchical superior was observed in the post-test. No significant differences were found in the nurses’ job satisfaction and emotional competence after the implementation of the SafeCare Model.

CONCLUSION: The SafeCare Model needs improvement, suggesting increasing the amount of training time administered to nurses and strengthening the healthcare institution’s link to the Model.

PMID:34320147 | DOI:10.1590/0034-7167-2021-0125