Evidence Synthesis for Complex Interventions Using Meta-Regression Models

This study was funded by the Canadian Institutes of Health Research (grants FDN-143269 and FRN-123345) and a research fellowship held by K.J.K. (Frederick Banting and Charles Best Canada Graduate Scholarship GSD-134936). N.M.I. holds a Canada Research Chair (Tier 2) in Implementation of Evidence Based Practice and a Clinician Scientist Award from the Department of Family and Community Medicine at the University of Toronto (Toronto, Ontario, Canada). J.M.G. held a Canada Research Chair in Health Knowledge Transfer and Uptake during the time of the study’s conduct and was supported by a Foundation Grant from the Canadian Institutes of Health Research. D.M. was supported by a University of Ottawa Research Chair during the time of study conduct.Peer reviewedPublisher PD

Accelerated Diagnostic Protocols Using High-sensitivity Troponin Assays to “Rule In” or “Rule Out” Myocardial Infarction in the Emergency Department : A Systematic Review

Publisher PD

Computer Simulation on the Cooperation of Functional Molecules during the Early Stages of Evolution

It is very likely that life began with some RNA (or RNA-like) molecules, self-replicating by base-pairing and exhibiting enzyme-like functions that favored the self-replication. Different functional molecules may have emerged by favoring their own self-replication at different aspects. Then, a direct route towards complexity/efficiency may have been through the coexistence/cooperation of these molecules. However, the likelihood of this route remains quite unclear, especially because the molecules would be competing for limited common resources. By computer simulation using a Monte-Carlo model (with “micro-resolution” at the level of nucleotides and membrane components), we show that the coexistence/cooperation of these molecules can occur naturally, both in a naked form and in a protocell form. The results of the computer simulation also lead to quite a few deductions concerning the environment and history in the scenario. First, a naked stage (with functional molecules catalyzing template-replication and metabolism) may have occurred early in evolution but required high concentration and limited dispersal of the system (e.g., on some mineral surface); the emergence of protocells enabled a “habitat-shift” into bulk water. Second, the protocell stage started with a substage of “pseudo-protocells”, with functional molecules catalyzing template-replication and metabolism, but still missing the function involved in the synthesis of membrane components, the emergence of which would lead to a subsequent “true-protocell” substage. Third, the initial unstable membrane, composed of prebiotically available fatty acids, should have been superseded quite early by a more stable membrane (e.g., composed of phospholipids, like modern cells). Additionally, the membrane-takeover probably occurred at the transition of the two substages of the protocells. The scenario described in the present study should correspond to an episode in early evolution, after the emergence of single “genes”, but before the appearance of a “chromosome” with linked genes