Abstract Atrial fibrillation (AF) is an extremely common clinical problem with an important population morbidity and mortality burden. The management of AF is complex and fraught with many uncertain ...and contentious issues, which are being addressed by extensive ongoing basic and clinical research. The Canadian Cardiovascular Society AF Guidelines Committee produced an extensive set of evidence-based AF management guidelines in 2010 and updated them in the areas of anticoagulation and rate/rhythm control in 2012. In late 2013, the committee judged that sufficient new information regarding AF management had become available since 2012 to warrant an update to the Canadian Cardiovascular Society AF Guidelines. After extensive evaluation of the new evidence, the committee has updated the guidelines for: (1) stroke prevention principles; (2) anticoagulation of AF patients with chronic kidney disease; (3) detection of AF in patients with stroke; (4) investigation and management of subclinical AF; (5) left atrial appendage closure in stroke prevention; (6) emergency department management of AF; (7) periprocedural anticoagulation management; and (8) rate and rhythm control including catheter ablation. This report presents the details of the updated recommendations, along with their background and rationale. In addition, a complete set of presently applicable recommendations, those that have been updated and those that remain in force from previous guideline versions, is provided in the Supplementary Material.
Understanding the spatiotemporal patterns of emergence and circulation of new human seasonal influenza virus variants is a key scientific and public health challenge. The global circulation patterns ...of influenza A/H3N2 viruses are well characterized, but the patterns of A/H1N1 and B viruses have remained largely unexplored. Here we show that the global circulation patterns of A/H1N1 (up to 2009), B/Victoria, and B/Yamagata viruses differ substantially from those of A/H3N2 viruses, on the basis of analyses of 9,604 haemagglutinin sequences of human seasonal influenza viruses from 2000 to 2012. Whereas genetic variants of A/H3N2 viruses did not persist locally between epidemics and were reseeded from East and Southeast Asia, genetic variants of A/H1N1 and B viruses persisted across several seasons and exhibited complex global dynamics with East and Southeast Asia playing a limited role in disseminating new variants. The less frequent global movement of influenza A/H1N1 and B viruses coincided with slower rates of antigenic evolution, lower ages of infection, and smaller, less frequent epidemics compared to A/H3N2 viruses. Detailed epidemic models support differences in age of infection, combined with the less frequent travel of children, as probable drivers of the differences in the patterns of global circulation, suggesting a complex interaction between virus evolution, epidemiology, and human behaviour.
Abstract In February the World Health Organisation (WHO) recommends influenza viruses to be included in influenza vaccines for the forthcoming winter in the Northern Hemisphere. These recommendations ...are based on data collected by National Influenza Centres (NICs) through the WHO Global Influenza Surveillance and Response System (GISRS) and a more detailed analysis of representative and potential antigenically variant influenza viruses from the WHO Collaborating Centres for Influenza (WHO CCs) and Essential Regulatory Laboratories (ERLs). This article provides a detailed summary of the antigenic and genetic properties of viruses and additional background data used by WHO experts during development of the recommendations of the 2013–2014 Northern Hemisphere influenza vaccine composition.
Abstract Influenza vaccines form an important component of the global response against infections and subsequent illness caused in man by influenza viruses. Twice a year, in February and September, ...the World Health Organisation through its Global Influenza Surveillance Network (GISN), recommends appropriate influenza viruses to be included in the seasonal influenza vaccine for the upcoming Northern and Southern Hemisphere winters. This recommendation is based on the latest data generated from many sources and the availability of viruses that are suitable for vaccine manufacture. This article gives a summary of the data and background to the recommendations for the 2009–2010 Northern Hemisphere influenza vaccine formulation.
The administration of ketones to induce a mild ketosis is of interest for the alleviation of symptoms associated with various neurological disorders. This study aimed to understand the ...pharmacokinetics (PK) of
d
-β-hydroxybutyrate (BHB) and quantify the sources of variability following a dose of (
R
)-3-hydroxybutyl (
R
)-3-hydroxybutyrate (ketone monoester). Healthy volunteers (
n
= 37) were given a single drink of the ketone monoester, following which, 833 blood BHB concentrations were measured. Two formulations and five dose levels of ketone monoester were used. A nonlinear mixed effect modelling approach was used to develop a population PK model. A one compartment disposition model with negative feedback effect on endogenous BHB production provided the best description of the data. Absorption was best described by two consecutive first-order inputs and elimination by dual processes involving first-order (
CL
= 10.9 L/h) and capacity limited elimination (
V
max
= 4520 mg/h). Covariates identified were formulation (on relative oral bioavailable fraction and absorption rate constant) and dose (on relative oral bioavailable fraction). Lean body weight (on first-order clearance) and sex (on apparent volume of distribution) were also significant covariates. The PK of BHB is complicated by complex absorption process, endogenous production and nonlinear elimination. Formulation and dose appear to strongly influence the kinetic profile following ketone monoester administration. Further work is needed to quantify mechanisms of absorption and elimination of ketones for therapeutic use in the form of ketone monoester.
From both a fundamental and a clinical point of view, it is necessary to know the distribution of the eye's aberrations in the normal population and to be able to describe them as efficiently as ...possible. We used a modified Hartmann-Shack wave-front sensor to measure the monochromatic wave aberration of both eyes for 109 normal human subjects across a 5.7-mm pupil. We analyzed the distribution of the eye's aberrations in the population and found that most Zernike modes are relatively uncorrelated with each other across the population. A principal components analysis was applied to our wave-aberration measurements with the resulting principal components providing only a slightly more compact description of the population data than Zernike modes. This indicates that Zernike modes are efficient basis functions for describing the eye's wave aberration. Even though there appears to be a random variation in the eye's aberrations from subject to subject, many aberrations in the left eye were found to be significantly correlated with their counterparts in the right eye.
To develop a corneal model to better explain how refractive surgery procedures induce spherical aberration.
Department of Ophthalmology and Center for Visual Science, University of Rochester, ...Rochester, New York, USA.
The preoperative cornea was modeled as a rotationally symmetric surface with various radii of curvature and asphericities. The postoperative cornea was defined as the difference between the preoperative cornea and an ablation thickness profile computed based on the Munnerlyn equation. A ray-tracing program and Zernike polynomial fitting were used to calculate the induced amount of spherical aberration assuming a fixed ablation depth per pulse or a variable ablation depth depending on the incidence angle of each pulse on the cornea. A biological eye model of the corneal surface change after laser refractive surgery was also developed to explain the induced spherical aberrations after myopic and hyperopic treatments.
The clinical data showed that positive spherical aberration was induced after myopic correction and negative spherical aberration increased after hyperopic correction. In contrast, assuming a fixed ablation depth per pulse, the theoretical prediction was that negative spherical aberration with myopic treatment and positive spherical aberration with hyperopic treatment would increase. However, when assuming a variable ablation depth per pulse caused by non-normal incidence of laser spot on the cornea, the theoretically predicted induction of spherical aberration tends to fit better with the myopic and hyperopic clinical data. The effect of a variable ablation depth accounted for approximately half the clinically observed amount of spherical aberration. The biological model of the corneal surface change used to explain this remaining discrepancy showed the magnitude of the biological response in myopic correction is 3 times smaller than in hyperopic correction and that the direction of the biological response in hyperopic treatment is opposite that in myopic treatment.
This nontoric eye model, which separates the effects of differences in ablation efficiency and biological corneal surface change quantitatively, explains how spherical aberration is induced after myopic and hyperopic laser refractive surgery. With the corneal topographic data, this model can be incorporated into the ablation algorithm to decrease induced spherical aberrations, improving the outcomes of conventional and customized treatments.
Individuals' memory experiences typically covary with those of others' around them, and on average, an item is more likely to be familiar if a companion recommends it as such. Although it would be ...ideal if observers could use the external recommendations of others' as statistical priors during recognition decisions, it is currently unclear how or if they do so. Furthermore, understanding the sensitivity of recognition judgments to such external cues is critical for understanding memory conformity and eyewitness suggestibility phenomena. To address this we examined recognition accuracy and confidence following cues from an external source (e.g., "Likely Old") that forecast the likely status of upcoming memory probes. Three regularities emerged. First, hit and correct-rejection rates expectedly fell when participants were invalidly versus validly cued. Second, hit confidence was generally higher than correct-rejection confidence, regardless of cue validity. Finally, and most noteworthy, cue validity interacted with judgment confidence such that validity heavily influenced the confidence of correct rejections but had no discernible influence on the confidence of hits. Bootstrap-informed Monte Carlo simulation supported a dual process recognition model under which familiarity and recollection processes counteract to heavily dampen the influence of external cues on average reported confidence. A 3rd experiment tested this model using source memory. As predicted, because source memory is heavily governed by contextual recollection, cue validity again did not affect confidence, although as with recognition it clearly altered accuracy.
Highlights ► We provide data used for selection of the 2012 southern hemisphere influenza vaccine. ► Influenza activity for the 2011 southern hemisphere season was low or moderate. ► Co-circulation ...of A(H1N1)pdm09, A(H3N2) and influenza B viruses continued. ► No change was recommended for the 2012 vaccine composition comparing with 2011.
It is often assumed that observers seek to maximize correct responding during recognition testing by actively adjusting a decision criterion. However, early research by Wallace (Journal of ...Experimental Psychology: Human Learning and Memory 4:441–452,
1978
) suggested that recognition rates for studied items remained similar, regardless of whether or not the tests contained distractor items. We extended these findings across three experiments, addressing whether detection rates or observer confidence changed when participants were presented standard tests (targets and distractors) versus “pure-list” tests (lists composed entirely of targets or distractors). Even when observers were made aware of the composition of the pure-list test, the endorsement rates and confidence patterns remained largely similar to those observed during standard testing, suggesting that observers are typically not striving to maximize the likelihood of success across the test. We discuss the implications for decision models that assume a likelihood ratio versus a strength decision axis, as well as the implications for prior findings demonstrating large criterion shifts using target probability manipulations.
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