Effective Feedback to Improve Primary Care Prescribing Safety (EFIPPS) a pragmatic three-arm cluster randomised trial:designing the intervention (ClinicalTrials.gov registration NCT01602705)

Peer reviewedPublisher PD

Model simulations of the Bay of Fundy Gyre : 1. Climatological results

Author Posting. © American Geophysical Union, 2008. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 113 (2008): C10027, doi:10.1029/2007JC004480.The characteristics of a persistent gyre in the mouth of the Bay of Fundy are studied using model simulations. A set of climatological runs are conducted to evaluate the relative importance of the different forcing mechanisms affecting the gyre. The main mechanisms are tidal rectification and density-driven circulation. Stronger circulation of the gyre occurs during the later part of the stratified season (July–August and September–October). The density-driven flow around the gyre is set up by weak tidal mixing in the deep basin in the central Bay of Fundy and strong tidal mixing on the shallow flanks around Grand Manan Island and western Nova Scotia. Spring river discharge has an important influence on near-surface circulation but only a small effect when averaged over the entire water column. Retention of particles in the gyre is controlled by the residual tidal circulation, increased frontal retention during stratified periods, wind stress, and interactions with the adjacent circulation of the Gulf of Maine. Residence times longer than 30 days are predicted for particles released in the proximity of the gyre.The preparation of this paper was supported by NSF grant OCE-0430724 and NIEHS grant 1P50-ES01274201 (Woods Hole Center for Oceans and Human Health) and NOAA grant NA06NOS4780245 (GOMTOX). Additional support was provided by NSF grant DMS-0417769

Model simulations of the Bay of Fundy Gyre : 2. Hindcasts for 2005–2007 reveal interannual variability in retentiveness

Author Posting. © American Geophysical Union, 2009. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 114 (2009): C09005, doi:10.1029/2008JC004948.A persistent gyre at the mouth of the Bay of Fundy results from a combination of tidal rectification and buoyancy forcing. Here we assess recent interannual variability in the strength of the gyre using data assimilative model simulations. Realistic hindcast representations of the gyre are considered during cruises in 2005, 2006, and 2007. Assimilation of shipboard and moored acoustic Doppler current profiler velocities is used to improve the skill of the simulations, as quantified by comparison with nonassimilated drifter trajectories. Our hindcasts suggest a weakening of the gyre system during May 2005. Retention of simulated passive particles in the gyre during that period was highly reduced. A recovery of the dense water pool in the deep part of the basin by June 2006 resulted in a return to particle retention characteristics similar to climatology. Retention estimates reached a maximum during May 2007 (subsurface) and June–July 2007 (near surface). Interannual variability in the strength of the gyre was primarily modulated by the stratification of the dense water pool inside the Grand Manan Basin. These changes in stratification were associated with mixing conditions the preceding fall–winter and/or advectively driven modification of water mass properties.The preparation of this paper was supported by NSF grant OCE-0430724, NIEHS grant 1P50-ES01274201 (Woods Hole Center for Oceans and Human Health), andNOAAgrant NA06NOS4780245 (GOMTOX). Additional support was provided by NSF grant DMS-0417769

Sample size considerations for trials using cerebral white matter hyperintensity progression as an intermediate outcome at 1 year after mild stroke: Results of a prospective cohort study

Background: White matter hyperintensities (WMHs) are commonly seen on in brain imaging and are associated with stroke and cognitive decline. Therefore, they may provide a relevant intermediate outcome in clinical trials. WMH can be measured as a volume or visually on the Fazekas scale. We investigated predictors of WMH progression and design of efficient studies using WMH volume and Fazekas score as an intermediate outcome. Methods: We prospectively recruited 264 patients with mild ischaemic stroke and measured WMH volume, Fazekas score, age and cardiovascular risk factors at baseline and 1 year. We modelled predictors of WMH burden at 1 year and used the results in sample size calculations for hypothetical randomised controlled trials with different analysis plans and lengths of follow-up. Results: Follow-up WMH volume was predicted by baseline WMH: a 0.73-ml (95% CI 0.65-0.80, p < 0.0001) increase per 1-ml baseline volume increment, and a 2.93-ml increase (95% CI 1.76-4.10, p < 0.0001) per point on the Fazekas scale. Using a mean difference of 1 ml in WMH volume between treatment groups, 80% power and 5% alpha, adjusting for all predictors and 2-year follow-up produced the smallest sample size (n = 642). Other study designs produced samples sizes from 2054 to 21,270. Sample size calculations using Fazekas score as an outcome with the same power and alpha, as well as an OR corresponding to a 1-ml difference, were sensitive to assumptions and ranged from 2504 to 18,886. Conclusions: Baseline WMH volume and Fazekas score predicted follow-up WMH volume. Study size was smallest using volumes and longer-term follow-up, but this must be balanced against resources required to measure volumes versus Fazekas scores, bias due to dropout and scanner drift. Samples sizes based on Fazekas scores may be best estimated with simulation studies

High methylmercury in Arctic and subarctic ponds is related to nutrient levels in the warming eastern Canadian Arctic

Permafrost thaw ponds are ubiquitous in the eastern Canadian Arctic, yet little information exists on their potential as sources of methylmercury (MeHg) to freshwaters. They are microbially active and conducive to methylation of inorganic mercury, and are also affected by Arctic warming. This multiyear study investigated thaw ponds in a discontinuous permafrost region in the Subarctic taiga (Kuujjuarapik-Whapmagoostui, QC) and a continuous permafrost region in the Arctic tundra (Bylot Island, NU). MeHg concentrations in thaw ponds were well above levels measured in most freshwater ecosystems in the Canadian Arctic (>0.1 ng L−1). On Bylot, ice-wedge trough ponds showed significantly higher MeHg (0.3−2.2 ng L−1) than polygonal ponds (0.1−0.3 ng L−1) or lakes (<0.1 ng L−1). High MeHg was measured in the bottom waters of Subarctic thaw ponds near Kuujjuarapik (0.1−3.1 ng L−1). High water MeHg concentrations in thaw ponds were strongly correlated with variables associated with high inputs of organic matter (DOC, a320, Fe), nutrients (TP, TN), and microbial activity (dissolved CO2 and CH4). Thawing permafrost due to Arctic warming will continue to release nutrients and organic carbon into these systems and increase ponding in some regions, likely stimulating higher water concentrations of MeHg. Greater hydrological connectivity from permafrost thawing may potentially increase transport of MeHg from thaw ponds to neighboring aquatic ecosystems

Utilization of Inhaled Corticosteroids by Hospital Patients with Chronic Obstructive Pulmonary Disease, with a Review and Update on the Current Literature

ABSTRACT Objective: To review the evidence-based literature on the role of inhaled corticosteroids (ICS) in the management of chronic obstructive pulmonary disease (COPD) and to assess the utilization of ICS in patients admitted to hospital with exacerbations of COPD.Methods: A MEDLINE search with the terms “chronic obstructive pulmonary disease”, “COPD management”, “inhaled corticosteroids”, and “inhaled steroids” was conducted for the period 1978 to 2003, to assess the published evidence for ICS therapy. A chart review of inpatients with a diagnosis of COPD exacerbation was conducted for the 13-month period January 1, 2000, to January 31, 2001.Results: The literature review identified some weaknesses in the published evidence. Patients have not always been treated optimally with bronchodilators, and different outcomes have been measured in different trials. Recent trials have shown a reduction in exacerbations, and there is probably a subpopulation that would benefit from ICS. A total of 103 patients (46 men and 57 women) were identified for the chart review. Fifty-one (50%) of these patients had a prescription for ICS. However, bronchodilator therapy was optimized for only 13 (27%) of 49 ICS users. Exsmokers receiving specialist care were more likely to be receiving an ICS. They were also more likely to be receiving oral theophylline, although no other historical or clinical factor leading to institution of ICS therapy could be identified. Fluticasone (28 patients or 55% of those receiving ICS therapy) was the most frequently prescribed ICS. Spirometry results were documented for only 77 patients (75%).Conclusions: Although smoking cessation and initiation of home oxygen therapy are the only accepted evidence-based diseasemodifying therapies for COPD, there has been a recent focus on adjuvant treatment with ICS as a disease-modifying therapy, in particular to prevent or reduce exacerbations. The literature review suggested that therapy for COPD should be encouraged and should adhere to recent national guidelines. Bronchodilation should be optimized — with focus on compliance, inhaler tech-nique, and optimal therapy with short-acting anticholinergics, ß2-agonists, or long-acting agents — before addition of ICS therapy is considered. Cost-effectiveness trials, along with consideration of advances in therapy, are necessary to identify the COPD patients most likely to benefit from ICS therapy.RÉSUMÉ Objectif : Examiner le rôle des corticostéroïdes en inhalation (CSI) dans le traitement de bronchopneumopathie chronique obstructive (BPCO) à partir d’une revue de la littérature sur les données fondées sur les résultats et évaluer l’utilisation des CSI chez les patients hospitalisés pour l’exacerbation de leur BPCO.Méthodes : On a effectué des recherches dans MEDLINE à l’aide des termes anglais « chronic obstructive pulmonary disease », « COPD management », « inhaled corticosteroids » et « inhaled steroids » pour la période s’échelonnant de 1978 à 2003, pour évaluer les données publiées sur le traitement par les CSI. On a évalué les dossiers des patients hospitalisés pour l’exacerbation de leur BPCO, pendant une période de treize mois s’échelonnant du 1er janvier 2000 au 31 janvier 2001.Résultats : L’examen de la littérature a révélé certaines faiblesses. En effet, les patients n’ont pas toujours reçu le traitement bronchodilatateur optimal, et différents résultats ont été mesurés dans divers essais. En revanche, de récentes études ont montré une réduction des exacerbations, et il semble y avoir une sous-population qui pourrait bénéficier des CSI. Au total, les dossiers médicaux de 103 patients (46 hommes et 57 femmes) ont été retenus pour évaluation. De ces patients, 51 (50 %) avaient reçu une prescription de CSI. Toutefois, le traitement bronchodilatateur n’a été optimisé que pour 13 (27 %) des 49 utilisateurs de CSI. Les anciens fumeurs soignés par un spécialiste étaient plus susceptibles de recevoir des CSI. Ils étaient aussi plus susceptibles de recevoir de la théophylline par voie orale, malgré qu’aucun autre facteur historique ou clinique commandant l’instauration du traitement par les CSI n’ait pu être identifié. Le fluticasone était le CSI le plus prescrit (28 ou 55 % des patients recevant des CSI). Les résultats de la spirométrie n’ont été documentés que chez 77 patients (75 %).Conclusions : Bien que l’arrêt du tabagisme et l’instauration de l’oxygénothérapie à domicile soient les seuls traitements de fond reconnus contre la BPCO qui sont fondés sur les résultats, on a accordé récemment de l’intérêt au traitement adjuvant par les CSI comme traitement modificateur de cette maladie, plus particulièrement pour en prévenir ou en réduire les exacerbations. L’analyse de la littérature porte à croire que le traitement des BPCO doit être encouragé et conforme aux récentes lignes directrices nationales. Le traitement bronchodilatateur doit être optimisé — en portant un intérêt particulier à l’observance, aux méthodes d’inhalation et au traitement par les anticholinergiques à action rapide, les bêta-agonistes ou les agents à libération prolongée — avant d’envisager l’ajout d’un CSI. Des études coûtefficacité et l’examen des avancées thérapeutiques sont nécessaires pour déterminer les patients atteints de BPCO qui sont le plus susceptible de bénéficier d’un traitement par les CSI

iOBPdb – A Database for Experimentally Determined Functional Characterization of Odorant Binding Proteins

Odorant binding proteins (OBPs) are extra-cellular proteins which solubilize and transport volatile organic compounds (VOCs). Thousands of OBPs have been identified through genome sequencing and hundreds have been characterized by fluorescence ligand binding assays in individual studies. There is a limited understanding of the comparative structure-function relations of OBPs, primarily due to a lack of a centralized database that relates OBP binding affinity and structure. Combining 215 functional studies containing 381 unique OBPs from 91 insect species we present a database, iOBPdb: https://iobpdb.herokuapp.com, of OBP binding affinities for 620 unique VOC targets. This initial database provides powerful search and associative capabilities for retrieving and analyzing OBP-VOC binding interaction data. We present our results in a variety of phylogenetic representations as well as providing the binding profiles of OBP groups to VOC functional moieties. Potential applications include development of molecular probes for biosensors, novel bioassays and drugs, targeted pesticides which inhibit VOC / OBP interactions, and understanding odor sensing and perception in the brain.Partial funding was received from WE-REACH program at the University of Washington through the RADx RAD program at NIDCR/NIH

iOBPdb A Database for Experimentally Determined Functional Characterization of Insect Odorant Binding Proteins

Abstract Odorant binding proteins (OBPs) are extra-cellular proteins that solubilize and transport volatile organic compounds (VOCs). Thousands of OBPs have been identified through genome sequencing, and hundreds have been characterized by fluorescence ligand binding assays in individual studies. There is a limited understanding of the comparative structure-function relations of OBPs, primarily due to a lack of a centralized database that relates OBP binding affinity and structure. Combining 181 functional studies containing 382 unique OBPs from 91 insect species, we present a database, iOBPdb, of OBP binding affinities for 622 individual VOC targets. This initial database provides powerful search and associative capabilities for retrieving and analyzing OBP-VOC binding interaction data. We have validated this dataset using phylogenetic mapping to determine the authenticity of the collected sequences and whether they cluster according to their assigned subfamilies. Potential applications include developing molecular probes for biosensors, novel bioassays and drugs, targeted pesticides that inhibit VOC/OBP interactions, and understanding odor sensing and perception in the brain

Database version 2

Odorant binding proteins (OBPs) are extra-cellular proteins which solubilize and transport volatile organic compounds (VOCs). Thousands of OBPs have been identified through genome sequencing and hundreds have been characterized by fluorescence ligand binding assays in individual studies. There is a limited understanding of the comparative structure-function relations of OBPs, primarily due to a lack of a centralized database that relates OBP binding affinity and structure. Combining 215 functional studies containing 381 unique OBPs from 91 insect species we present a database, iOBPdb: https://iobpdb.herokuapp.com, of OBP binding affinities for 620 unique VOC targets. This initial database provides powerful search and associative capabilities for retrieving and analyzing OBP-VOC binding interaction data. We present our results in a variety of phylogenetic representations as well as providing the binding profiles of OBP groups to VOC functional moieties. Potential applications include development of molecular probes for biosensors, novel bioassays and drugs, targeted pesticides which inhibit VOC / OBP interactions, and understanding odor sensing and perception in the brain.Partial funding was received from WE-REACH program at the University of Washington through the RADx RAD program at NIDCR/NIH