The role of biotransformation in the estrogenicity of xenobiotics

Vermeulen, N.P.E. [Promotor]Commandeur, J.N.M. [Copromotor

Systematic differences between Cochrane and non-Cochrane meta-analyses on the same topic: a matched pair analysis

BACKGROUND: Meta-analyses conducted via the Cochrane Collaboration adhere to strict methodological and reporting standards aiming to minimize bias, maximize transparency/reproducibility, and improve the accuracy of summarized data. Whether this results in differences in the results reported by meta-analyses on the same topic conducted outside the Cochrane Collaboration is an open question. METHODS: We conducted a matched-pair analysis with individual meta-analyses as the unit of analysis, comparing Cochrane and non-Cochrane reviews. Using meta-analyses from the cardiovascular literature, we identified pairs that matched on intervention and outcome. The pairs were contrasted in terms of how frequently results disagreed between the Cochrane and non-Cochrane reviews, whether effect sizes and statistical precision differed systematically, and how these differences related to the frequency of secondary citations of those reviews. RESULTS: Our search yielded 40 matched pairs of reviews. The two sets were similar in terms of which was first to publication, how many studies were included, and average sample sizes. The paired reviews included a total of 344 individual clinical trials: 111 (32.3%) studies were included only in a Cochrane review, 104 (30.2%) only in a non-Cochrane review, and 129 (37.5%) in both. Stated another way, 62.5% of studies were only included in one or the other meta-analytic literature. Overall, 37.5% of pairs had discrepant results. The most common involved shifts in the width of 95% confidence intervals that would yield a different statistical interpretation of the significance of results (7 pairs). Additionally, 20% differed in the direction of the summary effect size (5 pairs) or reported greater than a 2-fold difference in its magnitude (3 pairs). Non-Cochrane reviews reported significantly higher effect sizes (P < 0.001) and lower precision (P < 0.001) than matched Cochrane reviews. Reviews reporting an effect size at least 2-fold greater than their matched pair were cited more frequently. CONCLUSIONS: Though results between topic-matched Cochrane and non-Cochrane reviews were quite similar, discrepant results were frequent, and the overlap of included studies was surprisingly low. Non-Cochrane reviews report larger effect sizes with lower precision than Cochrane reviews, indicating systematic differences, likely reflective of methodology, between the two types of reviews that could generate different interpretations of the interventions under question

Systematic differences between Cochrane and non-Cochrane meta-analyses on the same topic: a matched pair analysis

BACKGROUND: Meta-analyses conducted via the Cochrane Collaboration adhere to strict methodological and reporting standards aiming to minimize bias, maximize transparency/reproducibility, and improve the accuracy of summarized data. Whether this results in differences in the results reported by meta-analyses on the same topic conducted outside the Cochrane Collaboration is an open question. METHODS: We conducted a matched-pair analysis with individual meta-analyses as the unit of analysis, comparing Cochrane and non-Cochrane reviews. Using meta-analyses from the cardiovascular literature, we identified pairs that matched on intervention and outcome. The pairs were contrasted in terms of how frequently results disagreed between the Cochrane and non-Cochrane reviews, whether effect sizes and statistical precision differed systematically, and how these differences related to the frequency of secondary citations of those reviews. RESULTS: Our search yielded 40 matched pairs of reviews. The two sets were similar in terms of which was first to publication, how many studies were included, and average sample sizes. The paired reviews included a total of 344 individual clinical trials: 111 (32.3%) studies were included only in a Cochrane review, 104 (30.2%) only in a non-Cochrane review, and 129 (37.5%) in both. Stated another way, 62.5% of studies were only included in one or the other meta-analytic literature. Overall, 37.5% of pairs had discrepant results. The most common involved shifts in the width of 95% confidence intervals that would yield a different statistical interpretation of the significance of results (7 pairs). Additionally, 20% differed in the direction of the summary effect size (5 pairs) or reported greater than a 2-fold difference in its magnitude (3 pairs). Non-Cochrane reviews reported significantly higher effect sizes (P < 0.001) and lower precision (P < 0.001) than matched Cochrane reviews. Reviews reporting an effect size at least 2-fold greater than their matched pair were cited more frequently. CONCLUSIONS: Though results between topic-matched Cochrane and non-Cochrane reviews were quite similar, discrepant results were frequent, and the overlap of included studies was surprisingly low. Non-Cochrane reviews report larger effect sizes with lower precision than Cochrane reviews, indicating systematic differences, likely reflective of methodology, between the two types of reviews that could generate different interpretations of the interventions under question

Pressure-induced Jahn-Teller suppression in Rb2CuCl4( H2O )2: Pseudo-Jahn-Teller effect

In this work we investigate the variation of the local structure around Cu2+ as well as the crystal structure in Rb2CuCl4(H2O)2 through x-ray absorption spectroscopy (XAS) and x-ray diffraction (XRD) as a function of pressure. We show that the application of pressure induces a local structural change in the Jahn-Teller (JT) CuCl4(H2O)22− complex from an axially elongated complex to a compressed one, yielding disappearance of the JT distortion related to the four in-plane Cl− ligands, which are responsible for the antiferrodistortive structure displayed by the crystal at ambient pressure. According to the Pseudo-Jahn-Teller (PJT) theory (electron-phonon coupling E⊗e), the presence of water ligands enhances the JT release at pressures well below the metallization pressure. The results are compared with recent pressure experiments on A2CuCl4 layered perovskites and heteronuclear CuCl4L2 complex series, L :Cl→H2O→NH3, and explained on the basis of the PJT model

Ethylene-mediated nitric oxide depletion pre-adapts plants to hypoxia stress

Timely perception of adverse environmental changes is critical for survival. Dynamic changes in gases are important cues for plants to sense environmental perturbations, such as submergence. In Arabidopsis thaliana, changes in oxygen and nitric oxide (NO) control the stability of ERFVII transcription factors. ERFVII proteolysis is regulated by the N-degron pathway and mediates adaptation to flooding-induced hypoxia. However, how plants detect and transduce early submergence signals remains elusive. Here we show that plants can rapidly detect submergence through passive ethylene entrapment and use this signal to pre-adapt to impending hypoxia. Ethylene can enhance ERFVII stability prior to hypoxia by increasing the NO-scavenger PHYTOGLOBIN1. This ethylene-mediated NO depletion and consequent ERFVII accumulation pre-adapts plants to survive subsequent hypoxia. Our results reveal the biological link between three gaseous signals for the regulation of flooding survival and identifies key regulatory targets for early stress perception that could be pivotal for developing flood-tolerant crops

Frictional behavior of oceanic transform faults and its influence on earthquake characteristics

Author Posting. © American Geophysical Union, 2012. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 117 (2012): B04315, doi:10.1029/2011JB009025.We use a three-dimensional strike-slip fault model in the framework of rate and state-dependent friction to investigate earthquake behavior and scaling relations on oceanic transform faults (OTFs). Gabbro friction data under hydrothermal conditions are mapped onto OTFs using temperatures from (1) a half-space cooling model, and (2) a thermal model that incorporates a visco-plastic rheology, non-Newtonian viscous flow and the effects of shear heating and hydrothermal circulation. Without introducing small-scale frictional heterogeneities on the fault, our model predicts that an OTF segment can transition between seismic and aseismic slip over many earthquake cycles, consistent with the multimode hypothesis for OTF ruptures. The average seismic coupling coefficient χ is strongly dependent on the ratio of seismogenic zone width W to earthquake nucleation size h*; χ increases by four orders of magnitude as W/h* increases from ∼1 to 2. Specifically, the average χ = 0.15 ± 0.05 derived from global OTF earthquake catalogs can be reached at W/h* ≈ 1.2–1.7. Further, in all simulations the area of the largest earthquake rupture is less than the total seismogenic area and we predict a deficiency of large earthquakes on long transforms, which is also consistent with observations. To match these observations over this narrow range of W/h* requires an increase in the characteristic slip distance dc as the seismogenic zone becomes wider and normal stress is higher on long transforms. Earthquake magnitude and distribution on the Gofar and Romanche transforms are better predicted by simulations using the visco-plastic model than the half-space cooling model.This work was supported by NSF-EAR award 1015221, NSF-OCE award 1061203, and a J. Lamar Worzel Assistant Scientist Fund to Y. Liu at WHOI.2012-10-2

Health-related quality of life and survival in liver transplant candidates.

Health-related quality of life (HRQOL) is an important measure of the effects of chronic liver disease in affected patients that helps guide interventions to improve well-being. However, the relationship between HRQOL and survival in liver transplant candidates remains unclear. We examined whether the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores from the Short Form 36 (SF-36) Health Survey were associated with survival in liver transplant candidates. We administered the SF-36 questionnaire (version 2.0) to patients in the Pulmonary Vascular Complications of Liver Disease study, a multicenter prospective cohort of patients evaluated for liver transplantation in 7 academic centers in the United States between 2003 and 2006. Cox proportional hazards models were used with death as the primary outcome and adjustment for liver transplantation as a time-varying covariate. The mean age of the 252 participants was 54 +/- 10 years, 64% were male, and 94% were white. During the 422 person years of follow-up, 147 patients (58%) were listed, 75 patients (30%) underwent transplantation, 49 patients (19%) died, and 3 patients were lost to follow-up. Lower baseline PCS scores were associated with an increased mortality rate despite adjustments for age, gender, Model for End-Stage Liver Disease score, and liver transplantation (P for the trend = 0.0001). The MCS score was not associated with mortality (P for the trend = 0.53). In conclusion, PCS significantly predicts survival in liver transplant candidates, and interventions directed toward improving the physical status may be helpful in improving outcomes in liver transplant candidates