Effect of statins on venous thromboembolic events: a meta-analysis of published and unpublished evidence from randomised controlled trials

Background - It has been suggested that statins substantially reduce the risk of venous thromboembolic events. We sought to test this hypothesis by performing a meta-analysis of both published and unpublished results from randomised trials of statins. Methods and Findings - We searched MEDLINE, EMBASE, and Cochrane CENTRAL up to March 2012 for randomised controlled trials comparing statin with no statin, or comparing high dose versus standard dose statin, with 100 or more randomised participants and at least 6 months' follow-up. Investigators were contacted for unpublished information about venous thromboembolic events during follow-up. Twenty-two trials of statin versus control (105,759 participants) and seven trials of an intensive versus a standard dose statin regimen (40,594 participants) were included. In trials of statin versus control, allocation to statin therapy did not significantly reduce the risk of venous thromboembolic events (465 [0.9%] statin versus 521 [1.0%] control, odds ratio [OR] = 0.89, 95% CI 0.78–1.01, p = 0.08) with no evidence of heterogeneity between effects on deep vein thrombosis (266 versus 311, OR 0.85, 95% CI 0.72–1.01) and effects on pulmonary embolism (205 versus 222, OR 0.92, 95% CI 0.76–1.12). Exclusion of the trial result that provided the motivation for our meta-analysis (JUPITER) had little impact on the findings for venous thromboembolic events (431 [0.9%] versus 461 [1.0%], OR = 0.93 [95% CI 0.82–1.07], p = 0.32 among the other 21 trials). There was no evidence that higher dose statin therapy reduced the risk of venous thromboembolic events compared with standard dose statin therapy (198 [1.0%] versus 202 [1.0%], OR = 0.98, 95% CI 0.80–1.20, p = 0.87). Risk of bias overall was small but a certain degree of effect underestimation due to random error cannot be ruled out. Please see later in the article for the Editors' Summary. Conclusions - The findings from this meta-analysis do not support the previous suggestion of a large protective effect of statins (or higher dose statins) on venous thromboembolic events. However, a more moderate reduction in risk up to about one-fifth cannot be ruled out

Introducing the diagrammatic semiotic mode

Peer reviewe

Semiotically-grounded distant viewing of diagrams : insights from two multimodal corpora

In this article, we argue for the benefits of combining large-scale analyses of visual materials currently pursued within digital humanities with insights from multimodality research, which is an emerging discipline that studies how human communication relies on appropriate combinations of expressive resources. We show that concepts developed within the field of multimodality research provide appropriate metadata schemes for various modes of expression in large corpora and datasets. We illustrate the proposed approach using a common mode of expression, diagrams, and analyse two recent multimodal diagram corpora using statistical and computational methods. Our results suggest that multimodally-motivated metadata schemes can provide a robust foundation for computational analyses of large corpora and datasets. Even if a corpus or dataset is not designed to support full-blown analyses of multimodal communication, our results imply that multimodality theory can still be used to impose tighter analytical control over a variety of visual materials.Peer reviewe

Introducing the diagrammatic semiotic mode

Peer reviewe

From data to patterns : on the role of models in empirical multimodality research

Peer reviewe

Systemic-functional linguistics and computation : New directions, new challenges

Peer reviewe

Development of a Time-Dependent Oral Colon Delivery System of Anaerobic Odoribacter splanchnicus for Bacteriotherapy

Odoribacter (O.) splanchnicus is an anaerobic member of the human intestinal microbiota. Its decrease in abundance has been associated with inflammatory bowel disease (IBD), non-alcoholic fatty liver, and cystic fibrosis. Considering the anti-inflammatory properties of O. splanchnicus and its possible use for IBD, intestinal isolate O. splanchnicus 57 was here formulated for oral colonic release based on a time-dependent strategy. Freeze-drying protocol was determined to ensure O. splanchnicus 57 viability during the process. Disintegrating tablets, containing the freeze-dried O. splanchnicus 57, were manufactured by direct compression and coated by powder-layering technique with hydroxypropyl methylcellulose (Methocel™ E50) in a tangential-spray fluid bed. Eudragit® L was then applied by spray-coating in a top-spray fluid bed. Double-coated tablets were tested for release, showing gastric resistance properties and, as desired, lag phases of reproducible duration prior to release in phosphate buffer pH 6.8. The cell viability and anti-inflammatory activity of the strain were assessed after the main manufacturing steps. While freeze-drying did not affect bacterial viability, the tableting and coating processes were more stressful. Nonetheless, O. splanchnicus 57 cells survived manufacturing and the final formulations had 106-107 CFU/g of viable cells. The strain kept its anti-inflammatory properties after tableting and coating, reducing Escherichia coli lipopolysaccharide-induced interleukin-8 cytokine release from HT-29 cells. Overall, O. splanchnicus 57 strain was formulated successfully for oral colon delivery, opening new ways to formulate pure cultures of single anaerobic strains or mixtures for oral delivery

Automatic Atrial Threshold Measurement and Adjustment in Pediatric Patients

Background: Automatic threshold measurement and output adjustment are used as default settings in modern pacemakers. The purpose of the study was to assess Atrial Capture Management (ACM) of Medtronic pacemakers in pediatric patients. Methods: Forty children were enrolled in two centers. Median age was 9.8 years (range 0.8–17.5 years). Half had undergone surgery for congenital heart defects; 45% of patients had an epicardial atrial lead. The pacing indication was atrioventricular block in 82% of patients and sinus node disease in 18%. Manually determined atrial thresholds and ACM measurements were compared. Results: ACM measurements were within the expected variation in 37/40 (93%) of the patients. In one patient the threshold was 0.625-V lower manually than with ACM. One patient had too high an intrinsic atrial rate for ACM to be able to measure threshold. The mean threshold at 0.4 ms was 0.69 ± 0.32 V manually and 0.68 ± 0.35 V with ACM (two-tailed paired t- test, P = 0.52) in all patients. The mean difference was 0.012 V (95% confidence interval: −0.027, 0.053). The mean endocardial threshold was 0.70 ± 0.36 V manually and 0.69 ± 0.38 V with ACM; epicardial threshold was 0.67 ± 0.27 V manually and 0.68 ± 0.32 V with ACM. The difference between the measurements was 0.012 V for endocardial and 0.014 V for epicardial leads. No atrial arrhythmias due to ACM measurements were observed. Conclusions: ACM measures atrial thresholds reliably in pediatric patients with both endocardial and epicardial leads, allowing its use in both. Constant high intrinsic atrial rate may prevent automatic threshold measurement in young children. (PACE 2010; 33:309–313)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79326/1/j.1540-8159.2009.02619.x.pd

AI2D-RST : A multimodal corpus of 1000 primary school science diagrams

This article introduces AI2D-RST, a multimodal corpus of 1000 English-language diagrams that represent topics in primary school natural sciences, such as food webs, life cycles, moon phases and human physiology. The corpus is based on the Allen Institute for Artificial Intelligence Diagrams (AI2D) dataset, a collection of diagrams with crowdsourced descriptions, which was originally developed to support research on automatic diagram understanding and visual question answering. Building on the segmentation of diagram layouts in AI2D, the AI2D-RST corpus presents a new multi-layer annotation schema that provides a rich description of their multimodal structure. Annotated by trained experts, the layers describe (1) the grouping of diagram elements into perceptual units, (2) the connections set up by diagrammatic elements such as arrows and lines, and (3) the discourse relations between diagram elements, which are described using Rhetorical Structure Theory (RST). Each annotation layer in AI2D-RST is represented using a graph. The corpus is freely available for research and teaching.Peer reviewe

BopA does not have a major role in the adhesion of bifidobacterium bifidum to intestinal epithelial cells, extracellular matrix proteins, and mucus

he ability of bifidobacteria to adhere to the intestine of the human host is considered to be important for efficient colonization and achieving probiotic effects. Bifidobacterium bifidum strains DSM20456 and MIMBb75 adhere well to the human intestinal cell lines Caco-2 and HT-29. The surface lipoprotein BopA was previously described to be involved in mediating adherence of B. bifidum to epithelial cells, but thioacylated, purified BopA inhibited the adhesion of B. bifidum to epithelial cells in competitive adhesion assays only at very high concentrations, indicating an unspecific effect. In this study, the role of BopA in the adhesion of B. bifidum was readdressed. The gene encoding BopA was cloned and expressed without its lipobox and hydrophobic signal peptide in Escherichia coli, and an antiserum against the recombinant BopA was produced. The antiserum was used to demonstrate the abundant localization of BopA on the cell surface of B. bifidum. However, blocking of B. bifidum BopA with specific antiserum did not reduce adhesion of bacteria to epithelial cell lines, arguing that BopA is not an adhesin. Also, adhesion of B. bifidum to human colonic mucin and fibronectin was found to be BopA independent. The recombinant BopA bound only moderately to human epithelial cells and colonic mucus, and it failed to bind to fibronectin. Thus, our results contrast the earlier findings on the major role of BopA in adhesion, indicating that the strong adhesion of B. bifidum to epithelial cell lines is BopA independent