Epistasis between mutations can make adaptation contingent on evolutionary history. Yet despite widespread 'microscopic' epistasis between the mutations involved, microbial evolution experiments show consistent patterns of fitness increase between replicate lines. Recent work shows that this consistency is driven in part by global patterns of diminishing-returns and increasing-costs epistasis, which make mutations systematically less beneficial (or more deleterious) on fitter genetic backgrounds. However, the origin of this 'global' epistasis remains unknown. Here, we show that diminishing-returns and increasing-costs epistasis emerge generically as a consequence of pervasive microscopic epistasis. Our model predicts a specific quantitative relationship between the magnitude of global epistasis and the stochastic effects of microscopic epistasis, which we confirm by reanalyzing existing data.  https://www.selleckchem.com/products/dir-cy7-dic18.html  We further show that the distribution of fitness effects takes on a universal form when epistasis is widespread and introduce a novel fitness landscape model to show how phenotypic evolution can be repeatable despite sequence-level stochasticity.
  To evaluate predictions of moderate-to-severe-obstructive sleep apnea (MS-OSA) by the neck circumference height ratio (NHR) and waist circumference height ratio (WHR) and compare to the derived STOP-Bang Questionnaire (dSBQ) prediction.
 
  Included were 6,167 participants from the Sleep Heart Health Study (SHHS) baseline evaluation who completed polysomnograms, had anthropometric measurements, and data to compute proxy dSBQ item answers. The sample was divided randomly into derivation (n = 2,035) and validation (n = 4,132) subsets. The derivation sample was used to estimate the NHR and WHR cut points to detect MS-OSA; the validation sample was used to evaluate sensitivity (SN) and specificity (SP).
 
  Mean age was 63.1 years, and 47.2% were male for the overall sample. In the derivation sample, a cut point ≥ 0.21 for NHR yielded a SN of 92.0% and SP of 25.0%; a cut point ≥ 0.52 for WHR yielded a SN of 91.2% and SP of 25.0% for MS-OSA. Using the validation sample, the NHR, WHR, and dSBQ areas under the receiver operator curves (AUCs) were 69.8%, 65.2%, and 70.5% respectively for MS-OSA. There was no statistical difference with listwise comparison of the NHR and dSBQ AUCs (p = 0.997); however, there was a significant difference between the WHR and dSBQ AUCs (p = 0.015) for MS-OSA.
 
  The NHR is a viable OSA screening tool comparable to the dSBQ, independent of witnessed apneas and BMI, that can be used for different body types.
 The NHR is a viable OSA screening tool comparable to the dSBQ, independent of witnessed apneas and BMI, that can be used for different body types.
  Sleep fragmentation (SF) has been reported to be associated with cardiovascular risk. The aim of this study was to explore the relationship between SF and congestive heart failure (CHF).
 
  A total of 4,887 participants (2,256 males and 2,631 females, mean age of 63.6 ± 11.0 years) from the Sleep Heart Health Study (SHHS) were included in this study. Incident CHF was defined as the first occurrence of CHF between baseline in-home polysomnography (PSG) and the end of follow-up. Objective assessments for SF, including sleep fragmentation index (SFI), arousal index (ArI), sleep efficiency (SE), and wake after sleep onset (WASO), were determined based on in-home polysomnography records. Multivariate Cox regression analysis was used to investigate the relationship between SF and incident CHF.
 
  During an average of 10 years of follow-up, 543 participants with CHF (11.1%) were observed. Individuals with CHF had a significantly higher SFI, total ArI, and WASO and a lower SE than controls. After multivariate Cox regression analysis, SE (odds ratio [OR], 0.967; 95% confidence interval [CI] 0.955-0.978; P < 0.001), WASO (OR, 1.009; 95% CI 1.006-1.012; P < 0.001), SFI (OR, 1.046; CI 1.007-1.086; P = 0.021), and total ArI (OR, 1.018; 95% CI 1.000-1.035; P = 0.044) were found to be associated with the incidence of CHF in participants without hypertension.
 
  Objectively measured SF was associated with the incidence of CHF. The role of SFI, total ArI, SE, and WASO deserves further investigation.
 Objectively measured SF was associated with the incidence of CHF. The role of SFI, total ArI, SE, and WASO deserves further investigation.
  Patients with end-stage kidney disease (ESKD) commonly experience sleep disturbances. Sleep disturbance has been inconsistently associated with mortality risk in hemodialysis patients, but the burden of symptoms from sleep disturbances has emerged as a marker that may shed light on these discrepancies and guide treatment decisions. This study examines whether functional outcomes of sleep are associated with increased risk of intermediary CV outcomes or mortality among adults initiating hemodialysis.
 
  In 228 participants enrolled in the Predictors of Arrhythmic and Cardiovascular risk in ESRD (PACE) study, the Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10), which assesses functional outcomes of daytime sleepiness, was administered within 6 months of enrollment. Intermediary CV outcomes included QTc [ms], heart rate variance [ms²], left ventricular mass index [g/m², LVMI], and left ventricular hypertrophy [LVH]. The association of FOSQ-10 score with all-cause mortality was examined using proportionas at increased risk for cardiovascular complications and death.Posttraumatic stress disorder (PTSD) is a common mental disorder following traumatic events. The present study was conducted to understand the prevalence of PTSD after the earthquake in Iran and Pakistan. The review includes all articles published from inception to March 2019. The pooled prevalence for overall PTSD was 55.6% (95% CI 49.9-61.3). It was 60.2% (95% CI 54.1-66.3) and 49.2% (95% CI 39.4-59) for Iranian and Pakistani survivors, respectively. Women experienced higher incidence of PTSD than men. The variation of PTSD based on the clinical interview was lower than the self-report approach. The interval time between the earthquakes and the assessment showed that the prevalence of PTSD decreased over time. The prevalence of PTSD in Iran and Pakistan was higher than the global average, and the rate of the disorder in Iran was higher than in Pakistan. Sex, method of assessment, and time lag between the occurrence of disaster and assessment of PTSD affect the prevalence.