Stepped wedge cluster randomized controlled trial designs: a review of reporting quality and design features

Background The stepped wedge (SW) cluster randomized controlled trial (CRCT) design is being used with increasing frequency. However, there is limited published research on the quality of reporting of SW-CRCTs. We address this issue by conducting a literature review. Methods Medline, Ovid, Web of Knowledge, the Cochrane Library, PsycINFO, the ISRCTN registry, and ClinicalTrials.gov were searched to identify investigations employing the SW-CRCT design up to February 2015. For each included completed study, information was extracted on a selection of criteria, based on the CONSORT extension to CRCTs, to assess the quality of reporting. Results A total of 123 studies were included in our review, of which 39 were completed trial reports. The standard of reporting of SW-CRCTs varied in quality. The percentage of trials reporting each criterion varied to as low as 15.4%, with a median of 66.7%. Conclusions There is much room for improvement in the quality of reporting of SW-CRCTs. This is consistent with recent findings for CRCTs. A CONSORT extension for SW-CRCTs is warranted to standardize the reporting of SW-CRCTs.This work was supported by the Wellcome Trust (grant number 099770/Z/12/Z to MJG); the Medical Research Council (grant number MC_UP_1302/2 to APM) and the National Institute for Health Research Cambridge Biomedical Research Centre (MC_UP_1302/4 to JMSW)

Centrifuge modelling of building response to tunnel excavation

Understanding the building response to tunnelling-induced settlements is an important aspect of urban tunnelling in soft ground. Previous centrifuge modelling research demonstrated significant potential to study this tunnel–soil–structure interaction problem. However, these recent studies were limited by simplified building models, which might result in uncertainties when interpreting the building performance to tunnelling subsidence. This paper presents an experimental modelling procedure and the results of a series of centrifuge tests, involving relatively complex surface structures subjected to tunnelling in sand. Powder-based three-dimensional (3D) printing was adopted to fabricate building models with realistic layouts, facade openings and foundations. The 3D printed material had a Young's modulus and a brittle response similar to historic masonry. Modelling effects and boundary conditions are quantified. The good agreement between the experimentally obtained results and previous research demonstrates that the soil–structure interaction during tunnel excavation is well replicated. The experimental procedure provides a framework to quantify how building features affect the response of buildings to tunnelling subsidence.The authors are grateful to EPSRC grant EP/K018221/1 and Crossrail for the financial support

The effects of accumulated Pheide <i>a</i> on the transcript levels of chlorophyll breakdown pathway genes during dark-induced senescence.

<p>(A–E) qRT-PCR analysis of mRNA abundance of chlorophyll catabolic genes (<i>SGR</i>, <i>NYC1</i>, <i>PPH</i>, <i>PAO</i> and <i>RCCR</i>) in wild type and the indicated mutant leaves during dark-induced senescence. <i>ACTIN2</i> was used as the internal standard. Error bars indicate standard deviations of three technical replicates, and the results were consistent in three biological replicates.</p

Nitric Oxide Deficiency Accelerates Chlorophyll Breakdown and Stability Loss of Thylakoid Membranes during Dark-Induced Leaf Senescence in Arabidopsis

<div><p>Nitric oxide (NO) has been known to preserve the level of chlorophyll (Chl) during leaf senescence. However, the mechanism by which NO regulates Chl breakdown remains unknown. Here we report that NO negatively regulates the activities of Chl catabolic enzymes during dark-induced leaf senescence. The transcriptional levels of the major enzyme genes involving Chl breakdown pathway except for <em>RED CHL CATABOLITE REDUCTASE</em> (<em>RCCR</em>) were dramatically up-regulated during dark-induced Chl degradation in the leaves of Arabidopsis NO-deficient mutant <em>nos1/noa1</em> that exhibited an early-senescence phenotype. The activity of pheide <em>a</em> oxygenase (PAO) was higher in the dark-induced senescent leaves of <em>nos1/noa1</em> compared with wild type. Furthermore, the knockout of <em>PAO</em> in <em>nos1/noa1</em> background led to pheide <em>a</em> accumulation in the double mutant <em>pao1 nos1/noa1</em>, which retained the level of Chl during dark-induced leaf senescence. The accumulated pheide <em>a</em> in darkened leaves of <em>pao1 nos1/noa1</em> was likely to inhibit the senescence-activated transcriptional levels of Chl catabolic genes as a feed-back inhibitory effect. We also found that NO deficiency led to decrease in the stability of photosynthetic complexes in thylakoid membranes. Importantly, the accumulation of pheide <em>a</em> caused by <em>PAO</em> mutations in combination with NO deficiency had a synergistic effect on the stability loss of thylakoid membrane complexes in the double mutant <em>pao1 nos1/noa1</em> during dark-induced leaf senescence. Taken together, our findings have demonstrated that NO is a novel negative regulator of Chl catabolic pathway and positively functions in maintaining the stability of thylakoid membranes during leaf senescence.</p> </div

Analysis of chlorophyll contents during dark-induced leaf senescence.

<p>Chlorophyll contents were measured in the detached leaves of the indicated genotypes during a 6-d-dark treatment. Data are means of three replicates. Error bars indicate SD.</p

Supplementary Figure 4 from Cdk4/6 Inhibition Induces Epithelial–Mesenchymal Transition and Enhances Invasiveness in Pancreatic Cancer Cells

PDF file, 1109K, Effects of cdk4 and cdk6 knockdown on EMT in PANC-1 cells.</p

Baseline-Covariate Adjusted Confidence Interval for Proportional Difference Between Two Treatment Groups in Clinical Trials

The treatment effect of a therapeutic product on a binary endpoint is often expressed as the difference in proportions of subjects with the outcome of interest between the treated and control groups of a clinical trial. Analysis of the proportional difference and construction of the associated confidence interval (CI) is often complicated due to the baseline covariate(s) being associated with the primary endpoint. Analysis adjusting for such baseline covariate(s) generally improves efficiency of hypothesis testing and precision of treatment effect estimation, and avoids possible bias caused by baseline covariate imbalances. Most existing literatures focus on constructing unadjusted or categorical covariate(s) adjusted only CI, which provides very limited advice on how different statistical methods perform and which method is optimal in terms of constructing both categorical and continuous baseline covariate(s) adjusted CI for proportional difference. We review and compare the performance of three commonly used model-based methods as well as the traditional nonparametric weighted-difference methods for the construction of covariate-adjusted CI for proportional difference via a real data application and simulations. The coverage of 95% CI, Type I error control, and power are examined. We also examine the factors leading to the model convergence failure in different scenarios via simulations.</p

Novel Highly Efficient Macrophotoinitiator Comprising Benzophenone, Coinitiator Amine, and Thio Moieties for Photopolymerization

To investigate the photoefficiency differences between the macrophotoinitiator and the polymerizable photoinitiator, a novel thio-containing macrophotoinitiator P(MTPBP-co-DMAEMA) bearing side-chain benzophenone and coinitiator amine was synthesized through free radical copolymerization of a polymerizable photoinitiator 4-[(4-maleimido)thiophenyl]benzophenone (MTPBP) and an unsaturated coinitiator amine N,N-dimethylaminoethyl methacrylate (DMAEMA). To determine the influences of coinitiator amine on photopolymerization, a macroamine P(DMAEMA) was also synthesized through homopolymerization of DMAEMA for comparison. FT-IR, 1H NMR, and gel permeation chromatography (GPC) analyses confirmed the structures of the two polymers. The UV−vis spectra of macrophotoinitiator P(MTPBP-co-DMAEMA) and polymerizable photoinitiator MTPBP are similar, and both exhibit high red-shifted maximum of absorption compared with benzophenone. Photopolymerization of 1,6-hexanediol diacrylate (HDDA) and trimethylolpropane triacrylate (TMPTA), initiated by benzophenone/DMAEMA, MTPBP/DMAEMA, MTPBP/P(DMAEMA), and P(MTPBP-co-DMAEMA) systems, was studied by differential scanning photocalorimetry (photo-DSC). The results indicate that P(MTPBP-co-DMAEMA) is most efficient for the polymerization of both HDDA and TMPTA. As for the photopolymerization of HDDA, the final conversion runs up to 98%. However, the photoefficiency of the MTPBP/P(DMAEMA) system, with macroamine as coinitiator, is unsatisfactory

Supplementary Figure 5 from Cdk4/6 Inhibition Induces Epithelial–Mesenchymal Transition and Enhances Invasiveness in Pancreatic Cancer Cells

PDF file, 398K, Effects of cdk4 and cdk6 knockdown on Smad transcriptional activity.</p

The moderating effect of SDSP on the relationship between PSI and INT.

The moderating effect of SDSP on the relationship between PSI and INT.</p