Antithrombotic therapy in patients receiving saphenous vein coronary artery bypass grafts: a protocol for a systematic review and network meta-analysis.

INTRODUCTION: The current evidence for the prevention of saphenous vein graft failure (SVGF) after coronary artery bypass graft (CABG) surgery consists of direct head-to-head comparison of treatments (including placebo) in randomised-controlled trials (RCTs) and observational studies. However, summarising the evidence using traditional pairwise meta-analyses does not allow the inclusion of data from treatments that have not been compared head to head. Exclusion of such comparisons could impact the precision of pooled estimates in a meta-analysis. Hence, to address the challenge of whether aspirin alone or in addition to another antithrombotic agent is a more effective regimen to improve SVG patency, a network meta-analysis (NMA) is necessary. The objectives of this study are to synthesise the available evidence on antithrombotic agents (or their combination) and estimate the treatment effects among direct and indirect treatment comparisons on SVGF and major adverse cardiovascular events, and to generate a treatment ranking according to their efficacy and safety outcomes. METHODS: We will perform a systematic review of RCTs evaluating antithrombotic agents in patients undergoing CABG. A comprehensive English literature search will be conducted using electronic databases and grey literature resources to identify published and unpublished articles. Two individuals will independently and in duplicate screen potential studies, assess the eligibility of potential studies and extract data. Risk of bias and quality of evidence will also be evaluated independently and in duplicate. We will investigate the data to ensure its suitability for NMA, including adequacy of the outcome data and transitivity of treatment effects. We plan to estimate the pooled direct, indirect and the mixed effects for all antithrombotic agents using a NMA. ETHICS AND DISSEMINATION: Due to the nature of the study, there are no ethical concerns nor informed consent required. We anticipate that this NMA will be the first to simultaneously assess the relative effects of multiple antithrombotic agents in patients undergoing CABG. The results of this NMA will inform clinicians, patients and guideline developers the best available evidence on comparative effects benefits of antithrombotic agents after CABG while considering the side effect profile to support future clinical decision-making. We will disseminate the results of our systematic review and NMA through a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42017065678

Heart field origin of great vessel precursors relies on nkx2.5-mediated vasculogenesis

The pharyngeal arch arteries (PAAs) are transient embryonic blood vessels that make indispensable contributions to the carotid arteries and great vessels of the heart, including the aorta and pulmonary artery1, 2. During embryogenesis, the PAAs appear in a craniocaudal sequence to connect pre-existing segments of the primitive circulation after de novo vasculogenic assembly from angioblast precursors3, 4. Despite the unique spatiotemporal characteristics of PAA development, the embryonic origins of PAA angioblasts and the genetic factors regulating their emergence remain unknown. Here, we identify the embryonic source of PAA endothelium as nkx2.5+ progenitors in lateral plate mesoderm long considered to adopt cell fates within the heart exclusively5, 6. Further, we report that PAA endothelial differentiation relies on Nkx2.5, a canonical cardiac transcription factor not previously implicated in blood vessel formation. Together, these studies reveal the heart field origin of PAA endothelium and attribute a novel vasculogenic function to the cardiac transcription factor nkx2.5 during great vessel precursor development

Investigating knowledge management factors affecting Chinese ICT firms performance: An integrated KM framework

This is an Author's Accepted Manuscript of an article published in the Journal of Information Systems Management, 28(1), 19 - 29, 2011, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/10580530.2011.536107.This article sets out to investigate the critical factors of Knowledge Management (KM) which are considered to have an impact on the performance of Chinese information and communication technology (ICT) firms. This study confirms that the cultural environment of an enterprise is central to its success in the context of China. It shows that a collaborated, trusted, and learning environment within ICT firms will have a positive impact on their KM performance

Cdk2 Is Required for p53-Independent G2/M Checkpoint Control

The activation of phase-specific cyclin-dependent kinases (Cdks) is associated with ordered cell cycle transitions. Among the mammalian Cdks, only Cdk1 is essential for somatic cell proliferation. Cdk1 can apparently substitute for Cdk2, Cdk4, and Cdk6, which are individually dispensable in mice. It is unclear if all functions of non-essential Cdks are fully redundant with Cdk1. Using a genetic approach, we show that Cdk2, the S-phase Cdk, uniquely controls the G2/M checkpoint that prevents cells with damaged DNA from initiating mitosis. CDK2-nullizygous human cells exposed to ionizing radiation failed to exclude Cdk1 from the nucleus and exhibited a marked defect in G2/M arrest that was unmasked by the disruption of P53. The DNA replication licensing protein Cdc6, which is normally stabilized by Cdk2, was physically associated with the checkpoint regulator ATR and was required for efficient ATR-Chk1-Cdc25A signaling. These findings demonstrate that Cdk2 maintains a balance of S-phase regulatory proteins and thereby coordinates subsequent p53-independent G2/M checkpoint activation

Chamber identity programs drive early functional partitioning of the heart

The vertebrate heart muscle (myocardium) develops from the first heart field (FHF) and expands by adding second heart field (SHF) cells. While both lineages exist already in teleosts, the primordial contributions of FHF and SHF to heart structure and function remain incompletely understood. Here we delineate the functional contribution of the FHF and SHF to the zebrafish heart using the cis-regulatory elements of the draculin (drl) gene. The drl reporters initially delineate the lateral plate mesoderm, including heart progenitors. Subsequent myocardial drl reporter expression restricts to FHF descendants. We harnessed this unique feature to uncover that loss of tbx5a and pitx2 affect relative FHF versus SHF contributions to the heart. High-resolution physiology reveals distinctive electrical properties of each heart field territory that define a functional boundary within the single zebrafish ventricle. Our data establish that the transcriptional program driving cardiac septation regulates physiologic ventricle partitioning, which successively provides mechanical advantages of sequential contraction

The relationship between organisational characteristics and the effects of clinical guidelines on medical performance in hospitals, a meta-analysis

We are grateful to our colleagues involved in the systematic review of guideline dissemination and implementation strategies across all settings especially Cynthia Fraser, Graeme MacLennan, Craig Ramsay, Paula Whitty, Martin Eccles, Lloyd Matowe, Liz Shirran. The systematic review of guideline dissemination and implementation strategies across all settings was funded by the UK NHS Health Technology Assessment Program. Dr Ruth Thomas is funded by a Wellcome Training Fellowship in Health Services Research. (Grant number GR063790MA). The Health Services Research Unit is funded by the Chief Scientists Office of the Scottish Executive Department of Health. Dr Jeremy Grimshaw holds a Canada Research Chair in Health Knowledge Transfer and Uptake. However the views expressed are those of the authors and not necessarily the funders.Peer reviewedPublisher PD

The association of academic tracking to depressive symptoms among adolescents in three Caribbean countries

<p>Abstract</p> <p>Background</p> <p>Students who are tracked into low performing schools or classrooms that limit their life chances may report increased depressive symptoms. Limited research has been conducted on academic tracking and its association with depressive symptoms among high school students in the Caribbean. This project examines levels of depressive symptoms among tenth grade students tracked within and between high schools in Jamaica, St. Vincent and St. Kitts and Nevis.</p> <p>Methods</p> <p>Students enrolled in grade ten of the 2006/2007 academic year in Jamaica, St. Kitts and Nevis and St. Vincent were administered the Beck Depression Inventory II (BDI-II). In Jamaica and St. Vincent, academic tracking was operationalized using data provided by the local Ministries of Education. These Ministries ranked ordered schools according to students' performance on Caribbean school leaving examinations. In St. Kitts and Nevis tracking was operationalized by classroom assignments within schools whereby students were grouped into classrooms according to their levels of academic achievement. Multiple regression analyses were conducted to examine the relationships between academic tracking and BDI-II depression scores.</p> <p>Results</p> <p>A wide cross-section of 4^thform students in each nation was sampled (n = 1738; 278 from Jamaica, 737 St. Kitts and Nevis, 716 from St. Vincent; 52% females, 46.2% males and 1.8% no gender reported; age 12 to 19 years, mean = 15.4 yrs, sd = .9 yr). Roughly half (53%) of the students reported some symptoms of depression with 19.2% reporting moderate and 10.7% reporting severe symptoms of depression. Students in Jamaica reported significantly higher depression scores than those in either St. Kitts and Nevis or St. Vincent (p < .01). Students assigned to a higher academic track reported significantly lower BDI-II scores than students who were assigned to the lower academic track (p < .01).</p> <p>Conclusions</p> <p>There appears to be an association between academic tracking and depressive symptoms that is differentially manifested across the islands of Jamaica, St. Kitts and Nevis and St. Vincent.</p