Probing dark contents in globular clusters with timing effects of pulsar acceleration

We investigate pulsar timing residuals due to the coupling effect of the pulsar transverse acceleration and the Römer delay. The effect is relatively small and usually negligible. Only for pulsars in globular clusters, it is possibly important. The maximum residual amplitude, which is from the pulsar near the surface of the core of the cluster, is about tens of nanoseconds, and may hardly be identified for most globular clusters currently. However, an intermediate-mass black hole in the center of a cluster can apparently increase the timing residual magnitudes. Particularly for pulsars in the innermost core region, their residual magnitudes may be significant. The high-magnitude residuals, which are above critical lines of each cluster, are strong evidence for the presence of a black hole or dark remnants of comparable total mass in the center of the cluster. We also explored the timing effects of line-of-sight accelerations for the pulsars. The distribution of measured line-of-sight accelerations are simulated with a Monte Carlo method. Two-dimensional Kolmogorov-Smirnov tests are performed to reexamine the consistency of distributions of the simulated and reported data for various values of parameters of the clusters. It is shown that the structure parameters of Terzan 5 can be constrained well by comparing the distribution of measured line-of-sight accelerations with the distributions from Monte Carlo simulations. We find that the cluster has an upper limit on the central black hole/dark remnant mass of ∼ 6000 M ⊙.

Factors Associated with Medicine Timing Effects: A Meta-analysis

Importance Clinical evidence suggests that the time of day of treatment can affect outcomes in many different diseases, but this information is dispersed, imprecise, and heterogeneous. Consequently, practice guidelines and clinical care recommendations seldom specify intervention time. Objective To understand the sources of variability and summarize clinical findings on the time of day effects of medicine. Data Sources A systematic search of Pubmed, Google Scholar, and ClinicalTrials.gov for chronotherapy OR time of administration. Study Selection Any clinical study since 2000, randomized or observational, that compared the effects of treatment at different times of day. We included pharmacologic or surgical interventions having at least one continuous outcome. Data Extraction and Synthesis For selected studies, we extracted the mean and variance of each time-of-day treatment group. From these, we computed the standardized mean difference (SMD) as the measure of timing effect. Where a study reported multiple outcomes, we selected a single outcome based on a defined order of priority. Main Outcomes and Measures We estimated overall pooled effect size and heterogeneity by a random effects model, followed by outlier detection and subgroup analyses to evaluate how study factors, including drug, design, outcome, and source, associate with timing effect. Results 78 studies met the inclusion criteria, comprising 48 distinct interventions over many therapeutic areas. We found an overall effect of time on clinical outcomes but with substantial heterogeneity between studies. Predicted effects range from none to large depending on the study context. Study size, registration status, and source are associated with the magnitude of effect. Larger trials and those that were pre-registered have markedly smaller effects, suggesting that the published record overstates the effects of the timing of medicine on clinical outcomes. In particular, the notion that antihypertensives are more effective if taken at bedtime draws disproportionately from one source in the field, which consistently detects larger effects than the community average. Lastly, among the most highly studied drug timing relationships, the aspirin anti-clotting effect stands out, consistently favoring evening over morning dosing. Conclusions and Relevance While accounts of drug timing effects have focused on yes/no, appreciating the range of probable effects may help clarify where circadian medicine meets the threshold for clinical benefit.

Epigenetic Modifications Associated with Maternal Anxiety during Pregnancy and Children’s Behavioral Measures

Epigenetic changes are associated with altered behavior and neuropsychiatric disorders and they modify the trajectory of aging. Maternal anxiety during pregnancy is a common environmental challenge for the fetus, causing changes in DNA methylation. Here, we determined the mediating role of DNA methylation and the moderating role of offspring sex on the association between maternal anxiety and children’s behavioral measures. In 83 mother–child dyads, maternal anxiety was assessed in each trimester of pregnancy when the child was four years of age. Children’s behavioral measures and children’s buccal DNA methylation levels (NR3C1, IGF2/H19 ICR, and LINE1) were examined. Higher maternal anxiety during the third trimester was associated with more methylation levels of the NR3C1. Moderating effects of sex on the association between maternal anxiety and methylation were found for IGF2/H19 and LINE1 CpGs. Mediation analysis showed that methylation of NR3C1 could buffer the effects of maternal anxiety on children’s behavioral measures, but this effect did not remain significant after controlling for covariates. In conclusion, our data support an association between maternal anxiety during pregnancy and DNA methylation. The results also underscore the importance of sex differences and timing effects. However, DNA methylation as underlying mechanism of the effect of maternal anxiety during pregnancy on offspring’s behavioral measures was not supported.

Number attraction in verb and anaphor production: narrowing a production–comprehension contrast

Although reflexive–antecedent agreement shows little susceptibility to number attraction in comprehension, prior production research using the preamble-completion paradigm has demonstrated attraction for both verbs and anaphora. In four production experiments, we compared number attraction effects on subject–verb and reflexive–antecedent agreement using a novel scene-description task in addition to a more traditional preamble elicitation paradigm. While the results from the preamble task align with prior findings, the more naturalistic scene description task produced the same contrast observed in comprehension, with robust verb attraction but minimal anaphor attraction. In addition to analyzing agreement error distributions, we also analyzed the production time-course of participant responses, finding timing effects that pattern with error distributions, even when no error is present. The results suggest that production agreement processes show similar profiles to comprehension processes. We discuss potential sources of variable susceptibility to agreement attraction, suggesting that differences may arise from the time-course of information processing across tasks and linguistic dependencies.