The multispecies coalescent provides an elegant theoretical framework for estimating species trees and species demographics from genetic markers. However, practical applications of the multispecies ...coalescent model are limited by the need to integrate or sample over all gene trees possible for each genetic marker. Here we describe a polynomial-time algorithm that computes the likelihood of a species tree directly from the markers under a finite-sites model of mutation effectively integrating over all possible gene trees. The method applies to independent (unlinked) biallelic markers such as well-spaced single nucleotide polymorphisms, and we have implemented it in SNAPP, a Markov chain Monte Carlo sampler for inferring species trees, divergence dates, and population sizes. We report results from simulation experiments and from an analysis of 1997 amplified fragment length polymorphism loci in 69 individuals sampled from six species of Ourisia (New Zealand native foxglove).
To determine the hormonal effects of reducing sleep duration under controlled feeding conditions.
Randomized, crossover study.
Inpatient.
Twenty-seven normal weight, 30- to 45-yr-old men and women ...habitually sleeping 7-9 hr/night.
PARTICIPANTS WERE STUDIED UNDER TWO SLEEP CONDITIONS: short (4 hr in bed) or habitual (9 hr in bed) sleep. A controlled diet was provided for each 4-day study period.
Fasting blood samples were obtained daily and frequent blood samples were obtained throughout day 4. The main outcomes measures included glucose, insulin, leptin, ghrelin, adiponectin, total glucagon-like peptide 1 (GLP-1) and peptide YY(3-36) (PYY(3-36)) concentrations. Body weights were reduced by 2.2 ± 0.4 lb and 1.7 ± 0.4 lb during the habitual and short sleep phases, respectively (both P < 0.0001). There was no effect of sleep duration on glucose, insulin, and leptin profiles (all P > 0.05). Ghrelin and GLP-1 responses differed by sex. Short sleep increased fasting (P = 0.054) and morning (08:00-12:00) (P = 0.042) total ghrelin in men but not women. The reverse was observed for GLP-1: afternoon levels (12:30-19:00) were lower (P = 0.016) after short sleep compared with habitual sleep in women but not men.
These data suggest that, in the context of negative energy balance, short sleep does not lead to a state of increased insulin resistance, but may predispose to overeating via separate mechanisms in men and women.
Trial registration on http://www.clinicaltrials.gov. #NCT00935402.
Abstract Objective To use a large population-level database to assess survival outcomes for collecting duct renal cell carcinoma (CDRCC). Materials and methods The National Cancer Database was ...queried for all cases of CDRCC and clear cell renal cell carcinoma (CCRCC) from 2004 to 2013. After removing patients with other cancer diagnoses, the analytic cohort was composed of 201,686 CCRCC and 577 CDRCC cases. Kaplan-Meier and cox proportional hazards analysis were employed to model survival. Results Compared to CCRCC, patients with CDRCC presented with higher grade and stage, node positive, and metastatic disease (70.7% vs. 30.0% with metastasis; P <0.001). Overall median survival for CDRCC was 13.2 months (95% CI: 11.0–15.5) compared to the 122.5 months (95% CI: 121.0–123.9) for CCRCC. On multivariate analysis of the CDRCC cohort, increasing T stage, high-grade disease, and metastasis were predictors of mortality. Of 184 patients with metastatic CDRCC, 113 underwent cytoreductive nephrectomy (CNx) whereas the rest were treated with chemo/radiation or observed. Survival outcomes were improved in patients who received both CNx with chemo/radiation compared to CNx alone (hazard ratio = 0.51, 95% CI: 0.32–0.79) or chemo/radiation alone (hazard ratio = 0.57, 95% CI: 0.37–0.89) on multivariate analysis. Conclusion CDRCC is an aggressive subtype of renal cell carcinoma. Median survival is 13 months after diagnosis, drastically lower than for CCRCC. More than 70% of patients have metastatic disease at diagnosis. Chemo/radiation in addition to CNx is associated with a survival benefit over single mode therapy.
To assess the effectiveness of a keratoconus-detection algorithm derived from Artemis very high-frequency (VHF) digital ultrasound (ArcScan Inc., Morrison, CO) epithelial thickness maps in the fellow ...eye from a series of patients with unilateral keratoconus.
The study included 10 patients with moderate to advanced keratoconus in one eye but a clinically and algorithmically topographically normal fellow eye. VHF digital ultrasound epithelial thickness data were acquired and a previously developed classification model was applied for identification of keratoconus to the clinically normal fellow eyes. Pentacam (Oculus Optikgeräte, Wetzlar, Germany) Belin-Ambrósio Enhanced Ectasia Display "D" score (BAD-D) data (5 of 10 eyes), and Orbscan (Bausch & Lomb, Rochester, NY) SCORE data (9 of 10 eyes) were also evaluated.
Five of the 10 fellow eyes were classified as keratoconic by the VHF digital ultrasound epithelium model. Five of 9 fellow eyes were classified as keratoconic by the SCORE model. For the 5 fellow eyes with Pentacam and VHF digital ultrasound data, one was classified as keratoconic by the VHF digital ultrasound model, one (different) eye by a combined VHF digital ultrasound and Pentacam model, and none by BAD-D alone.
Under the assumption that keratoconus is a bilateral but asymmetric disease, half of the 'normal' fellow eyes could be found to have keratoconus using epithelial thickness maps. The Orbscan SCORE or the combination of topographic BAD-D criteria with epithelial maps did not perform better.
Areas of increased lung attenuation visualized by computed tomography are associated with all-cause mortality in the general population. It is uncertain whether this association is attributable to ...interstitial lung disease (ILD).
To determine whether high-attenuation areas are associated with the risk of ILD hospitalization and mortality in the general population.
We performed a cohort study of 6,808 adults aged 45-84 years sampled from six communities in the United States. High-attenuation areas were defined as the percentage of imaged lung volume with attenuation values between -600 and -250 Hounsfield units. An adjudication panel determined ILD hospitalization and death.
After adjudication, 52 participants had a diagnosis of ILD during 75,232 person-years (median, 12.2 yr) of follow-up. There were 48 hospitalizations attributable to ILD (crude rate, 6.4 per 10,000 person-years). Twenty participants died as a result of ILD (crude rate, 2.7 per 10,000 person-years). High-attenuation areas were associated with an increased rate of ILD hospitalization (adjusted hazard ratio, 2.6 per 1-SD increment in high-attenuation areas; 95% confidence interval, 1.9-3.5; P < 0.001), a finding that was stronger among men, African Americans, and Hispanics. High-attenuation areas were also associated with an increased rate of ILD-specific death (adjusted hazard ratio, 2.3; 95% confidence interval, 1.7-3.0; P < 0.001). Our findings were consistent among both smokers and nonsmokers.
Areas of increased lung attenuation are a novel risk factor for ILD hospitalization and mortality. Measurement of high-attenuation areas by screening and diagnostic computed tomography may be warranted in at-risk adults.
This article presents a dataset of body composition, strength and performance measurements in older adults; the data were collected as part of Rancho Bernardo Study (RBS), a longitudinal ...observational cohort study. All community dwelling adults in Rancho Bernardo, California between 1972 and 1974 were eligible for participation in the study. A subset of the participants returned every four years for subsequent visits. The dataset in this publication consists of some of the measures taken in Visits 7–10, for 1466 subjects who had at least one of these measures taken. We analysed the data with a feed-forward loop model fitted by structural equation modelling. The data can be valuable for modelling and extracting further information on how body composition, strength and performance affect each other over a long period of time. The data are analysed and interpreted in the research article RoyChoudhury et al., 2019.
•Are there similarities in executive attention pathophysiology following TBI and in normal age-related decline?.•We derived a biomarker of executive attention pathophysiology that was common to both ...aging-related and post-TBI-related impairments, and in moderate-severe TBI.•Our findings identify biomarkers to track recovery, impact of interventions and guide development of targeted therapeutics following brain injuries.
Executive attention impairments are a persistent and debilitating consequence of traumatic brain injury (TBI). To make headway towards treating and predicting outcomes following heterogeneous TBI, cognitive impairment specific pathophysiology first needs to be characterized. In a prospective observational study, we measured EEG during the attention network test aimed at detecting alerting, orienting, executive attention and processing speed. The sample (N = 110) of subjects aged 18–86 included those with and without traumatic brain injury: n = 27, complicated mild TBI; n = 5, moderate TBI; n = 10, severe TBI; n = 63, non-brain-injured controls. Subjects with TBI had impairments in processing speed and executive attention. Electrophysiological markers of executive attention processing in the midline frontal regions reveal that, as a group, those with TBI and elderly non-brain-injured controls have reduced responses. We also note that those with TBI and elderly controls have responses that are similar for both low and high-demand trials. In subjects with moderate-severe TBI, reductions in frontal cortical activation and performance profiles are both similar to that of controls who are ∼4 to 7 years older. Our specific observations of frontal response reductions in subjects with TBI and in older adults is consistent with the suggested role of the anterior forebrain mesocircuit as underlying cognitive impairments. Our results provide novel correlative data linking specific pathophysiological mechanisms underlying domain-specific cognitive deficits following TBI and with normal aging. Collectively, our findings provide biomarkers that may serve to track therapeutic interventions and guide development of targeted therapeutics following brain injuries.
We present an estimation of divergence time-range based on a coalescent model. This model sum the probability of coalescent trees, taking into account the effect of incomplete lineage sorting. ...Maximum likelihood estimate based on this model has been computed previously; however, a formula for divergence time-range estimate or confidence interval has never been presented for this model as the expression of the likelihood makes this estimation difficult to compute. Our formula for the divergence time-range estimate can be readily coded into a program. We did not use a simulation or resampling-based approach and therefore our method is fast and less computationally intensive. We demonstrate that our method is much faster and as accurate a simulation-based approach.
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