Activity

© 2020 Optometry Australia.Molecular and behavioral timekeeping is regulated by the circadian system which includes the brain’s suprachiasmatic nucleus (SCN) that translates environmental light information into neuronal and endocrine signals aligning peripheral tissue rhythms to the time of day. Despite the critical role of circadian rhythms in fertility, it remains unexplored how circadian rhythms change within reproductive tissues during pregnancy. To determine how estrous cycle and pregnancy impact phase relationships of reproductive tissues, we used PER2Luciferase (PER2LUC) circadian reporter mice and determined the time of day of PER2LUC peak (phase) in the SCN, pituitary, uterus, and ovary. The relationships between reproductive tissue PER2LUC phases changed throughout the estrous cycle and late pregnancy and were accompanied by changes to PER2LUC period in the SCN, uterus, and ovary. To determine if the phase relationship adaptations were driven by sex steroids, we asked if progesterone, a hormone involved in estrous cyclicity and pregnancy, could regulate Per2-luciferase expression. Using an in vitro transfection assay, we found that progesterone increased Per2-luciferase expression in immortalized SCN (SCN2.2) and arcuate nucleus (KTAR) cells. In addition, progesterone shortened PER2LUC period in ex vivo uterine tissue recordings collected during pregnancy. As progesterone dramatically increases during pregnancy, we evaluated wheel-running patterns in PER2LUC mice. We confirmed that activity levels decrease during pregnancy and found that activity onset was delayed. Although SCN, but not arcuate nucleus, PER2LUC period changed during late pregnancy, onset of locomotor activity did not correlate with SCN or arcuate nucleus PER2LUC period. Proteasome inhibitor © 2020 Wiley Periodicals, Inc.AIM To describe pediatric post-discharge concerns manifesting in the first 96 hours after hospital discharge. DESIGN Analysis of nursing documentation generated as part of a randomized controlled trial evaluating the effect of a nurse home visit on healthcare re-use. METHODS We analyzed home visit records for 651 children (age less then 18) hospitalized at a large Midwestern children’s hospital in 2015 and 2016 who were enrolled in the trial. Registered nurses documented concerns in structured fields and free-text notes in visit records. Descriptive statistics were used to summarize visit documentation. Free-text visit notes were reviewed and exemplars illustrative of quantitative findings were selected. RESULTS Overall, nurses documented at least one concern in 56% (N=367) of visits. Most commonly, they documented concerns about medication safety (15% or 91 visits). Specifically, in 11% (N=58) of visits nurses were concerned that caregivers lacked a full understanding of medications and in 8% (N=49) of visrticle is protected by copyright. All rights reserved.Many late-phase clinical trials recruit subjects at multiple study sites. This introduces a hierarchical structure into the data that can result in a power-loss compared to a more homogeneous single-center trial. Building on a recently proposed approach to sample size determination, we suggest a sample size recalculation procedure for multicenter trials with continuous endpoints. The procedure estimates nuisance parameters at interim from noncomparative data and recalculates the sample size required based on these estimates. In contrast to other sample size calculation methods for multicenter trials, our approach assumes a mixed effects model and does not rely on balanced data within centers. It is therefore advantageous, especially for sample size recalculation at interim. We illustrate the proposed methodology by a study evaluating a diabetes management system. Monte Carlo simulations are carried out to evaluate operation characteristics of the sample size recalculation procedure using comparative as well as noncomparative data, assessing their dependence on parameters such as between-center heterogeneity, residual variance of observations, treatment effect size and number of centers. We compare two different estimators for between-center heterogeneity, an unadjusted and a bias-adjusted estimator, both based on quadratic forms. The type 1 error probability as well as statistical power are close to their nominal levels for all parameter combinations considered in our simulation study for the proposed unadjusted estimator, whereas the adjusted estimator exhibits some type 1 error rate inflation. Overall, the sample size recalculation procedure can be recommended to mitigate risks arising from misspecified nuisance parameters at the planning stage. © 2020 The Authors. Biometrical Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Sediment contamination in freshwater streams in urban areas is a recognized and growing concern. As a part of a comprehensive regional stream-quality assessment, streambed sediment was sampled from streams spanning a gradient of urban intensity in the Piedmont ecoregion of the southeastern United States. We evaluated relations between a broad suite of sediment contaminants (metals, current use pesticides, organochlorine pesticides, polychlorinated biphenyls, brominated diphenyl ethers, and polycyclic aromatic hydrocarbons), ambient sediment toxicity, and macroinvertebrate communities from 76 sites. Sediment toxicity was evaluated by conducting whole-sediment laboratory toxicity testing with the amphipod Hyalella azteca (28-day) and the midge Chironomus dilutus (10-day). Roughly one-third of the sediment samples were identified as toxic for at least one test-species-endpoint, although concentrations of contaminants infrequently exceeded toxicity benchmarks. Ratios of contaminant concentrations relative to their benchmarks, both individually and as summed benchmark quotients, were explored on a carbon-normalized and a dry-weight basis. Invertebrate taxa measures from ecological surveys tended to decline with increasing urbanization and with sediment contamination. Toxicity test endpoints were more strongly related to sediment contamination than invertebrate community measures were. Sediment chemistry and sediment toxicity provided moderate and weak, respectively, explanatory power for the similarity/dissimilarity of invertebrate communities. This study indicates that current single-chemical sediment benchmarks may underestimate the effects from mixtures of sediment contaminants experienced by lotic invertebrates. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.