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Literary authors, especially those with other occupations, must come to grips with the question of why they should write at all, when the world urges them to devote their time and energy to other pursuits. They must reach, at the very least, a provisional conclusion regarding the relation between the uncertain value of their literary efforts and the more immediate values of their non-authorial social identities. Geoffrey Chaucer, with his several middle-strata identities, grappled with this question in a remarkably searching, complex manner. In this book, Robert J. Meyer-Lee examines the multiform, dynamic meditation on the relation between literary value and social identity that Chaucer stitched into the heart of The Canterbury Tales. He traces the unfolding of this meditation through what he shows to be the tightly linked performances of Clerk, Merchant, Franklin and Squire, offering the first full-scale reading of this sequence.
The United Nations Convention on the Rights of Persons with Disabilities (CRPD) is increasingly used to civilize grassroots disabled persons' organizations (DPOs) around the world. The international disability rights movement actively promotes the CRPD's key norm that disabled persons mobilize in support of their rights under the Convention. The unintended consequence of these activities, however, is that local groups focused on social support and service provision, rather than disability-rights advocacy, are targeted for change. While the resources provided by international actors to grassroots organizations provide new opportunities, they also create barriers to local groups' ability to promote full civic participation of their members in the local community. Through a detailed account of grassroots DPOs in Nicaragua, Civilizing Disability Society demonstrates how local organizations navigate pressures from abroad as they attempt to concretely address the health, education and economic needs of their members at home.
Polarimetric studies of pulsars at low radio frequencies provide important observational insights into the pulsar emission mechanism and beam models, and probe the properties of the magneto-ionic interstellar medium (ISM). Aperture arrays are the main form of next-generation low-frequency telescopes, including the Murchison Widefield Array (MWA). These require a distinctly different approach to data processing (e.g. calibration and beamforming) compared to traditional dish antennas. As the second paper of this series, we present a verification of the MWA’s pulsar polarimetry capability, using two bright southern pulsars, PSRs J0742–2822 and J1752–2806. Our observations simultaneously cover multiple frequencies (76–313 MHz) and were taken at multiple zenith angles (ZA) during a single night for each pulsar. We show that the MWA can be reliably calibrated for ZA ≲45° and frequencies ≲270 MHz. We present the polarimetric profiles for PSRs J0742–2822 and J1752–2806 at frequencies lower than 300 MHz for the first time, along with an analysis of the linear polarisation degree and pulse profile evolution with frequency. For PSR J0742–2822, the measured degree of linear polarisation shows a rapid decrease at low frequencies, in contrast with the generally expected trend, which can be attributed to depolarisation effects from small-scale, turbulent, magneto-ionic ISM components. This effect has not been widely explored for pulsars in general and will be further investigated in future work.
However well-regarded Chaucer’s works were during his lifetime, it was his immediate successors who fashioned him into the ‘father of English poetry’ they then bequeathed to the subsequent English literary tradition. In particular, the poets Thomas Hoccleve and John Lydgate not only represented Chaucer in this manner in their own, widely disseminated works, they were also instrumental in the broad dissemination of Chaucer’s works. Importantly, these activities were motivated not just by admiration but also by a politico-literary context in which Hoccleve and Lydgate, unlike Chaucer, were asked to produce works that spoke both for a prince and to a prince. Their invention of Chaucer’s literary authority cannot then be separated from their intervention into politics, and this conflation they also bequeathed to the English literary tradition, where it remained plainly visible in the works of their own successors, and where it persists, more obscurely, to the present.
Weed size can nfluence herbicide performance and herbicide interactions in mixtures. To control a broad range of species in soybean or cotton, POST herbicide mixtures will likely be commonplace in Roundup Ready® XtendFlex® and Enlist™ technologies. The impact of weed size on herbicide interactions that could occur in Roundup Ready XtendFlex or Enlist crops was assessed in two field experiments conducted in 2015 and 2016 at the Northeast Research and Extension Center in Keiser, AR. Combinations of glufosinate, glyphosate, dicamba, and 2,4-D were applied to either 10-cm or 30-cm weeds and evaluated for percent weed control, height reduction, and density reduction, collected 5 wk after treatment. Colby’s method was used to analyze treatments for herbicide interactions for control of barnyardgrass, Palmer amaranth, and pitted morningglory. Antagonism was identified with at least one treatment on all species. Almost all treatments were antagonistic for percent weed control, height reduction, and density reduction on barnyardgrass. When glyphosate in mixture with 2,4-D or dicamba was applied to 30-cm barnyardgrass, control declined 9% for both mixtures relative to glyphosate alone. Glufosinate plus glyphosate was antagonistic when applied to both 30-cm pitted morningglory and barnyardgrass. Glufosinate plus dicamba provided less control and density reduction of Palmer amaranth than what was expected from Colby’s equation. Overall, antagonism was more likely to be identified when applications were made to 30-cm weeds compared with 10-cm weeds. The utility of a given herbicide mixture will depend on the species present in the field and the size of those species at the time of application.
Species distribution models (SDMs) are statistical tools used to develop continuous predictions of species occurrence. ‘Integrated SDMs’ (ISDMs) are an elaboration of this approach with potential advantages that allow for the dual use of opportunistically collected presence-only data and site-occupancy data from planned surveys. These models also account for survey bias and imperfect detection through the use of a hierarchical modelling framework that separately estimates the species–environment response and detection process. This is particularly helpful for conservation applications and predictions for rare species, where data are often limited and prediction errors may have significant management consequences. Despite this potential importance, ISDMs remain largely untested under a variety of scenarios. We performed an exploration of key modelling decisions and assumptions on an ISDM using the endangered Baird’s tapir (Tapirus bairdii) as a test species. We found that site area had the strongest effect on the magnitude of population estimates and underlying intensity surface and was driven by estimates of model intercepts. Selecting a site area that accounted for the individual movements of the species within an average home range led to population estimates that coincided with expert estimates. ISDMs that do not account for the individual movements of species will likely lead to less accurate estimates of species intensity (number of individuals per unit area) and thus overall population estimates. This bias could be severe and highly detrimental to conservation actions if uninformed ISDMs are used to estimate global populations of threatened and data-deficient species, particularly those that lack natural history and movement information. However, the ISDM was consistently the most accurate model compared to other approaches, which demonstrates the importance of this new modelling framework and the ability to combine opportunistic data with systematic survey data. Thus, we recommend researchers use ISDMs with conservative movement information when estimating population sizes of rare and data-deficient species. ISDMs could be improved by using a similar parameterization to spatial capture–recapture models that explicitly incorporate animal movement as a model parameter, which would further remove the need for spatial subsampling prior to implementation.
One of the challenges with initiating long-acting injectable (LAI) antipsychotic regimens is achieving relevant drug levels quickly. After first injection of the LAI antipsychotic aripiprazole lauroxil (AL), the lag to reaching relevant plasma aripiprazole levels was initially addressed using supplemental oral aripiprazole for 21 days. A 1-day AL initiation regimen using a NanoCrystal® Dispersion formulation of AL (ALNCD; Aristada Initio®) combined with a single 30 mg dose of oral aripiprazole has been developed as an alternative approach. We compared the 1-day AL initiation regimen (ALNCD + 30 mg oral aripiprazole for 1 day) with the 21-day AL initiation regimen (AL + 15 mg/day of oral aripiprazole for 21 days) using kinetic modeling. Observed and modeled data demonstrate that the 1-day AL initiation regimen provides continuous aripiprazole exposure comparable to the 21-day AL initiation regimen. Each component of the 1-day AL initiation regimen (30 mg oral aripiprazole, ALNCD, and AL) contributes to aripiprazole plasma levels at different times, with oral aripiprazole predominating in the first week, then ALNCD and AL over time. In a double-blind, placebo-controlled, phase 1 study in patients with schizophrenia, the 1-day initiation regimen resulted in rapid achievement of relevant plasma aripiprazole levels comparable to those from the 21-day initiation regimen. Safety and tolerability of the 1-day regimen were consistent with the known profile of aripiprazole. Each part of the 1-day initiation regimen, together with AL, is necessary for continuous aripiprazole exposure from treatment initiation until the next regularly scheduled AL injection is administered.
Objectives: The Wisconsin Card Sorting Test (WCST) is a complex measure of executive function that is frequently employed to investigate the schizophrenia spectrum. The successful completion of the task requires the interaction of multiple intact executive processes, including attention, inhibition, cognitive flexibility, and concept formation. Considerable cognitive heterogeneity exists among the schizophrenia spectrum population, with substantive evidence to support the existence of distinct cognitive phenotypes. The within-group performance heterogeneity of individuals with schizophrenia spectrum disorder (SSD) on the WCST has yet to be investigated. A data-driven cluster analysis was performed to characterise WCST performance heterogeneity. Methods: Hierarchical cluster analysis with k-means optimisation was employed to identify homogenous subgroups in a sample of 210 schizophrenia spectrum participants. Emergent clusters were then compared to each other and a group of 194 healthy controls (HC) on WCST performance and demographic/clinical variables. Results: Three clusters emerged and were validated via altered design iterations. Clusters were deemed to reflect a relatively intact patient subgroup, a moderately impaired patient subgroup, and a severely impaired patient subgroup. Conclusions: Considerable within-group heterogeneity exists on the WCST. Identification of subgroups of patients who exhibit homogenous performance on measures of executive functioning may assist in optimising cognitive interventions. Previous associations found using the WCST among schizophrenia spectrum participants should be reappraised. (JINS, 2019, 25, 750–760)
Infections due to Campylobacter, Escherichia coli and Salmonella pose a significant health burden in Canada, resulting in major costs to the health care system and economic impacts due to lost productivity resulting from illness. Recent literature suggests that climate may play a role in the prevalence of these pathogens along the food chain. This study used integrated surveillance data to examine associations between weather variables, serving as a proxy for climate, in agricultural areas and Campylobacter, generic E. coli and Salmonella contamination on samples of beef, poultry and swine meat products in Canada. Various temperature metrics (average, maximum and variability) were correlated with Campylobacter prevalence along the food chain. The prevalence of E. coli and Salmonella was correlated with both precipitation and temperatures metrics; however, analysis for E. coli was limited to beef and swine meats at retail settings, because prevalence in other combinations approached 100%, which obviated further analysis. Campylobacter contamination in poultry and swine at abattoir and retail settings demonstrated a seasonal trend, with increased prevalence generally from June or July through November, compared to the baseline month of December. Based on these analyses, Campylobacter is the most likely foodborne bacteria studied whose occurrence in meat products is affected by climatic changes in Canada. An exploratory analysis of data at the provincial scale, using Ontario as an example, revealed similar directional relationships between climate and bacterial prevalence.
Introduction: Acute migraine headaches are common causes of presentation to the emergency department (ED). There is great variability in the efficacy of the available parenteral agents to manage pain, though triptans are among the recommended treatments. The objective of this systematic review was to update a previous review examining the effectiveness of parenteral agents for the treatment of acute migraine in the ED or equivalent acute care setting; our review examined pain management in emergency settings and assessed the effectiveness of triptan agents. Methods: A comprehensive search of 10 electronic databases and grey literature was conducted to supplement the previous systematic review. Two independent reviewers completed study selection, quality assessment, and data extraction. Any discrepancies were resolved by third party adjudication. Pain scale scores were analyzed using standardized mean difference (SMD) with 95% confidence intervals (CIs) calculated using a random effects model; heterogeneity (I2) was reported. Results: Titles and abstracts of 5039 unique studies were reviewed, of which, 51 studies were included. Sixty-four studies from the original review were included, resulting in a total of 115 included studies. Pain was measured within the ED or equivalent acute care setting using a variety of pain scales, most commonly the 0-10 cm or 100 mm visual analog scale. Four studies compared pain scores between patients receiving sumatriptan vs. other agents, of which, patients receiving sumatriptan reported higher pain scale scores (SMD = 0.53; 95% CI: 0.04, 1.02; I2 = 80%). In particular, patients receiving sumatriptan reported higher pain scale scores than patients receiving metoclopramide (SMD = 0.68; 95% CI: 0.31, 1.04; n = 1) or ketorolac (SMD = 1.39; 95% CI: 0.56, 2.21; n = 1). Overall, studies comparing anti-inflammatory agents (i.e., ketorolac or dexketoprofen) to other agents reported improved pain scale scores among patients receiving anti-inflammatory agents (SMD = -0.38; 95% CI: -0.73, -0.03; I2 = 66%; n = 5). Conclusion: Limited evidence suggests that patients treated with metoclopramide or anti-inflammatory agents experience greater pain reduction compared to patients treated with sumatriptan. This review will conduct a network analysis of parenteral agents to examine the comparative effectiveness of parenteral agents to manage pain among patients with acute migraine. Further analysis will also consider the balance between efficacy and adverse events.
Introduction: Although a variety of parenteral agents exist for the treatment of acute migraine, relapse after an emergency department (ED) visit is still a common occurrence. The objective of this systematic review was to update a previous review examining the effectiveness of parenteral agents for the treatment of acute migraine in the ED or equivalent acute care setting; our review focused on those studies aiming a reduction in relapse after an ED visit. Methods: A comprehensive search of 10 electronic databases and grey literature was conducted to identify comparative studies to supplement the previous systematic review. Two independent reviewers completed study selection, quality assessment, and data extraction. Any discrepancies were resolved by third party adjudication. Relative risks (RR) with 95% confidence intervals (CIs) were calculated using a random effects model and heterogeneity (I2) was reported. Results: Titles and abstracts of 5039 unique studies were reviewed, of which, 51 studies were included. Sixty-four studies from the original review were included, resulting in a total of 115 included studies. Relapse was reported in 44 (38%) included studies and occurred commonly in patients receiving placebo or no interventions (median = 39%; IQR: 14%, 47%). Overall, no differences in headache relapse were found between patients receiving sumatriptan or placebo (RR = 1.09; 95% CI: 0.55, 2.17; I2 = 93%; n = 8). Conversely, patients receiving neuroleptic agents experienced fewer relapses compared to placebo (RR = 0.27; 95% CI: 0.12, 0.58; I2 = 0%; n = 3); however, patients receiving neuroleptics reported an increase in adverse events (RR = 1.87; 95% CI: 1.17, 3.00; I2 = 0%; n = 3). Compared to placebo, patients receiving dexamethasone were less likely to experience a headache recurrence (RR = 0.71; 95% CI: 0.53, 0.95; I2 = 60%, n = 9); however, no differences were found in reported adverse events (RR = 1.09; 95% CI: 0.81, 1.47; I2 = 0%; n = 3). Conclusion: Relapse is a common occurrence for patients with migraine headaches. This review found patients receiving neuroleptics or dexamethasone experienced fewer headache recurrences. Conversely, triptan agents appear to have minimal effect on reducing the risk for headache recurrence following discharge from an acute care setting. Limited available data on adverse events is an important limitation to inform decision-making. Guidelines should be revised to reflect these results.
Background: Safety behaviours are ubiquitous across anxiety disorders and are associated with the aetiology, maintenance and exacerbation of anxiety. Cognitive behavioural models posit that beliefs about safety behaviours directly influence their use. Therefore, beliefs about safety behaviours may be an important component in decreasing safety behaviour use. Unfortunately, little empirical research has evaluated this theorized relationship.
Aims: The present study aimed to examine the predictive relationship between beliefs about safety behaviours and safety behaviour use while controlling for anxiety severity.
Method: Adults with clinically elevated levels of social anxiety (n = 145) and anxiety sensitivity (n = 109) completed an online survey that included established measures of safety behaviour use, quality of life, and anxiety severity. Participants also completed the Safety Behaviour Scale (SBS), a measure created for the current study which includes a transdiagnostic checklist of safety behaviours, as well as questions related to safety behaviour use and beliefs about safety behaviours.
Results: Within both the social anxiety and anxiety sensitivity groups, positive beliefs about safety behaviours predicted greater safety behaviour use, even when controlling for anxiety severity. Certain beliefs were particularly relevant in predicting safety behaviour use within each of the clinical analogue groups.
Conclusions: Findings suggest that efforts to decrease safety behaviour use during anxiety treatment may benefit from identifying and modifying positive beliefs about safety behaviours.
The aim of our study was to describe and to investigate the factors associated with glycopeptide-resistant enterococci (GRE) acquisition during a single-strain outbreak which occurred in several wards of hospital from September 2013 to January 2014. We designed a case–control study. Analyses were performed using Bayesian methods. Univariate logistic regressions with informative priors from published studies were conducted. A multivariate model was build including variables with a probability of odd-ratio exceeding one (Pr) >85% or <15%. Thirteen cases and 52 controls were recruited. The description of this outbreak highlighted the importance to quickly detect patients at risk of GRE carriage in order to implement the isolation measures and to transfer to dedicated department if they are effectively carriers. Following multivariate analysis, antibiotics during hospitalisation (Pr = 0.968), number of hospitalisation days in the year (Pr = 0.964), antacids intake (Pr = 0.878) (with a risk increase), immunosuppression (Pr = 0.026) and isolation measures (Pr = 0.003) (both with protective effect) were associated with GRE acquisition. The use of Bayesian statistics was useful because of our study's small population size and prior information availability.
A general computer program has been written in basic Fortran language and tested for computing average particle size, strain, and particle size distribution according to the Fourier method of B. E. Warren.
The program provides such optional features as input data and Fourier coefficient print out, automatic background correction, the choice of fixed count or fixed time input mode, the synthesized diffraction peaks deconvoluted with respect to the instrumental diffraction peak, and a variable amplification range of particle Size. Included in the analysis is a polynomial fitting procedure for the scattering factor. The authors have attempted to write this computer program to be as self-explanatory as possible for general applicability. This program is available on request.
This Fourier analysis program has been tested using known distribution functions, and has been used for measuring average particle size, particle size and strain distribution in heattreated boron-doped graphite samples.
Slow release is a fundamental feature of long-acting injectable (LAI) antipsychotics. This property allows continuous drug exposure between dosing intervals. However, there can be a significant delay between giving the first LAI dose and achievement of efficacious plasma concentrations. This time period requires additional pharmacologic intervention. Until now, this delay was addressed with one of two strategies: 1) continuing with supplemental oral antipsychotic, or 2) giving more LAI up front (e.g. loading dose). A third strategy has now been developed to reduce the time needed for oral supplementation when starting the LAI aripiprazole lauroxil (AL) from 21days to 1day. A nano-crystalline milled dispersion of AL (ALNCD; brand name ARISTADA INITIO™) was formulated by reducing the AL particle diameter from micron-size particles to nanometer- sized particles. ALNCD has faster dissolution and a shorter half-life than AL and is designed to be used as a single injection along with a single oral aripiprazole dose of 30mg as a 1-day alternative to the 21days of oral aripiprazole supplementation. Here we provide an overview of the new 1-day initiation regimen for starting AL treatment, and demonstrate the relative contributions of each of its components.
A blinded, randomized, phase 1, pharmacokinetic (PK), and safety study compared the 1-day initiation regimen with the 21-day oral aripiprazole regimen. A combination of observed data, and population pharmacokinetic model–based simulations were used to plot plasma aripiprazole concentrations of single doses of ALNCD, 30mg oral aripiprazole, and AL, individually, and all three combined.
The PK profiles of the 1-day and 21-day initiation regimens (both in conjunction with either 441mg or 882mg doses of AL) were comparable, with therapeutically relevant aripiprazole levels achieved within 4days of treatment initiation. The safety profile of the 1-day initiation regimen was similar to the 21-day initiation regimen, and consistent with that of AL. Aripiprazole concentration–time profiles demonstrated that each component delivered aripiprazole to the systemic circulation at different time periods, with the 30mg dose of oral aripiprazole predominant in the first week, followed by ALNCD, and then AL.
The 1-day initiation regimen is well-tolerated and a suitable alternative to 21days of oral aripiprazole supplementation for starting AL. Each component of the 1-day initiation regimen, together with AL, is necessary to provide continuous coverage from treatment initiation until the next regularly scheduled AL injection.
Funding Acknowledgements: This study was funded by Alkermes Inc.
Numerous health benefits are attributed to the n-3 long-chain PUFA (n-3 LCPUFA); EPA and DHA. A systematic literature review was conducted to investigate factors, other than diet, that are associated with the n-3 LCPUFA levels. The inclusion criteria were papers written in English, carried out in adult non-pregnant humans, n-3 LCPUFA measured in blood or tissue, data from cross-sectional studies, or baseline data from intervention studies. The search revealed 5076 unique articles of which seventy were included in the qualitative synthesis. Three main groups of factors potentially associated with n-3 LCPUFA levels were identified: (1) unmodifiable factors (sex, genetics, age), (2) modifiable factors (body size, physical activity, alcohol, smoking) and (3) bioavailability factors (chemically bound form of supplements, krill oil v. fish oil, and conversion of plant-derived α-linolenic acid (ALA) to n-3 LCPUFA). Results showed that factors positively associated with n-3 LCPUFA levels were age, female sex (women younger than 50 years), wine consumption and the TAG form. Factors negatively associated with n-3 LCPUFA levels were genetics, BMI (if erythrocyte EPA and DHA levels are <5·6 %) and smoking. The evidence for girth, physical activity and krill oil v. fish oil associated with n-3 LCPUFA levels is inconclusive. There is also evidence that higher ALA consumption leads to increased levels of EPA but not DHA. In conclusion, sex, age, BMI, alcohol consumption, smoking and the form of n-3 LCPUFA are all factors that need to be taken into account in n-3 LCPUFA research.