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literature search will be conducted using electronic databases and grey literature resources to identify published and unpublished articles.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

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

Systematic critical realist review of interventions designed to improve end-of-life care in care homes.

The demand for high-quality end-of-life care is rising. Frequently evidenced concerns about the provision of end-of-life in care homes relate to inter-disciplinary communication and engagement in advance care planning. A number of interventions employing different mechanisms have been designed to address these issues. Therefore, the aim of this systematic critical realist review was to describe and explain the effectiveness of interventions designed to improve end-of-life care in care homes. Electronic searches were conducted in ScienceDirect, MEDLINE, PubMed, PsychINFO, and CINAHL from January 2000 to August 2018. Forty one studies were included in the review. While most of the evidence identified in this review was not strong, there was evidence to suggest that education and inter-professional collaboration can be effective intervention mechanisms for improving end-of-life care in care homes. High staff turnover was a significant contextual mechanism impacting on the sustainability of interventions. In terms of human agency, it is important to note a consistent finding related to the dedication and enthusiasm of care home staff who deliver end-of-life care

Defective Cell Cycle Checkpoint Functions in Melanoma Are Associated with Altered Patterns of Gene Expression

Defects in DNA damage responses may underlie genetic instability and malignant progression in melanoma. Cultures of normal human melanocytes (NHMs) and melanoma lines were analyzed to determine whether global patterns of gene expression could predict the efficacy of DNA damage cell cycle checkpoints that arrest growth and suppress genetic instability. NHMs displayed effective G1 and G2 checkpoint responses to ionizing radiation-induced DNA damage. A majority of melanoma cell lines (11/16) displayed significant quantitative defects in one or both checkpoints. Melanomas with B-RAF mutations as a class displayed a significant defect in DNA damage G2 checkpoint function. In contrast the epithelial-like subtype of melanomas with wild-type N-RAS and B-RAF alleles displayed an effective G2 checkpoint but a significant defect in G1 checkpoint function. RNA expression profiling revealed that melanoma lines with defects in the DNA damage G1 checkpoint displayed reduced expression of p53 transcriptional targets, such as CDKN1A and DDB2, and enhanced expression of proliferation-associated genes, such as CDC7 and GEMININ. A Bayesian analysis tool was more accurate than significance analysis of microarrays for predicting checkpoint function using a leave-one-out method. The results suggest that defects in DNA damage checkpoints may be recognized in melanomas through analysis of gene expression

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