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In 2013, the national surveillance case definition for West Nile virus (WNV) disease was revised to remove fever as a criterion for neuroinvasive disease and require at most subjective fever for non-neuroinvasive disease. The aims of this project were to determine how often afebrile WNV disease occurs and assess differences among patients with and without fever. We included cases with laboratory evidence of WNV disease reported from four states in 2014. We compared demographics, clinical symptoms and laboratory evidence for patients with and without fever and stratified the analysis by neuroinvasive and non-neuroinvasive presentations. Among 956 included patients, 39 (4%) had no fever; this proportion was similar among patients with and without neuroinvasive disease symptoms. For neuroinvasive and non-neuroinvasive patients, there were no differences in age, sex, or laboratory evidence between febrile and afebrile patients, but hospitalisations were more common among patients with fever (P < 0.01). The only significant difference in symptoms was for ataxia, which was more common in neuroinvasive patients without fever (P = 0.04). Only 5% of non-neuroinvasive patients did not meet the WNV case definition due to lack of fever. The evidence presented here supports the changes made to the national case definition in 2013.
Major depressive disorder (MDD) is a leading cause of disease burden worldwide, with lifetime prevalence in the United States of 17%. Here we present the results of the first prospective, large-scale, patient- and rater-blind, randomized controlled trial evaluating the clinical importance of achieving congruence between combinatorial pharmacogenomic (PGx) testing and medication selection for MDD.
1,167 outpatients diagnosed with MDD and an inadequate response to ≥1 psychotropic medications were enrolled and randomized 1:1 to a Treatment as Usual (TAU) arm or PGx-guided care arm. Combinatorial PGx testing categorized medications in three groups based on the level of gene-drug interactions: use as directed, use with caution, or use with increased caution and more frequent monitoring. Patient assessments were performed at weeks 0 (baseline), 4, 8, 12 and 24. Patients, site raters, and central raters were blinded in both arms until after week 8. In the guided-care arm, physicians had access to the combinatorial PGx test result to guide medication selection. Primary outcomes utilized the Hamilton Depression Rating Scale (HAM-D17) and included symptom improvement (percent change in HAM-D17 from baseline), response (50% decrease in HAM-D17 from baseline), and remission (HAM-D17<7) at the fully blinded week 8 time point. The durability of patient outcomes was assessed at week 24. Medications were considered congruent with PGx test results if they were in the ‘use as directed’ or ‘use with caution’ report categories while medications in the ‘use with increased caution and more frequent monitoring’ were considered incongruent. Patients who started on incongruent medications were analyzed separately according to whether they changed to congruent medications by week8.
At week 8, symptom improvement for individuals in the guided-care arm was not significantly different than TAU (27.2% versus 24.4%, p=0.11). However, individuals in the guided-care arm were more likely than those in TAU to achieve remission (15% versus 10%; p<0.01) and response (26% versus 20%; p=0.01). Remission rates, response rates, and symptom reductions continued to improve in the guided-treatment arm until the 24week time point. Congruent prescribing increased to 91% in the guided-care arm by week 8. Among patients who were taking one or more incongruent medication at baseline, those who changed to congruent medications by week 8 demonstrated significantly greater symptom improvement (p<0.01), response (p=0.04), and remission rates (p<0.01) compared to those who persisted on incongruent medications.
Combinatorial PGx testing improves short- and long-term response and remission rates for MDD compared to standard of care. In addition, prescribing congruency with PGx-guided medication recommendations is important for achieving symptom improvement, response, and remission for MDD patients.
Funding Acknowledgements: This study was supported by Assurex Health, Inc.
Knowledge of species-specific spatial ecology is critical for applying appropriate management strategies to maximise conservation outcomes. We used radio-telemetry to describe spatial behaviour of the critically endangered, island-endemic Mariana Crow Corvus kubaryi. To determine whether management strategies should reflect life stage, we measured the home ranges and daily movements of 22 Mariana Crows. Fledgling mobility was low during the first 31 days post-fledging and effects of age (fledgling or sub-adult) and time (months post-fledging or post-dispersal) were often driven entirely by this period. After controlling for reduced fledgling mobility, cumulative home range size increased over time for both age classes and was, on average, more than twice the area for sub-adults than fledglings. Sub-adults also tended to make longer daily movements than fledglings. Non-cumulative, monthly home range areas did not increase over time but the average overlap in home range area between consecutive months was only 63%, suggesting large shifts in space use each month. These results highlight the dynamic nature of Mariana Crow home ranges and suggest that large-scale management efforts are critical for protecting both breeding and non-breeding individuals. The application of the traditional home range concept to Mariana Crows and other wide-ranging passerine birds may result in sub-optimal management strategies. Instead, we recommend that the spatial and temporal scale of conservation efforts be informed by species-specific spatial behaviour across all relevant life stages.
Antimicrobial stewardship (AS) involves the appropriate selection of antimicrobials. Antimicrobial stewardship programs are mandated in hospitals and are expanding to involve outpatient arenas. Multiple articles have been published describing the need for AS education for medical and pharmacy students, beginning early in the students’ career to develop into competent AS practitioners. Additionally, publications have described the role and impact of medical and pharmacy trainees on AS programs. Here, we review the published evidence describing medical and pharmacy trainees’ involvement in AS and call for future research in this area.
The genetic component of Cannabis Use Disorder may overlap with influences acting more generally on early stages of cannabis use. This paper aims to determine the extent to which genetic influences on the development of cannabis abuse/dependence are correlated with those acting on the opportunity to use cannabis and frequency of use.
A cross-sectional study of 3303 Australian twins, measuring age of onset of cannabis use opportunity, lifetime frequency of cannabis use, and lifetime DSM-IV cannabis abuse/dependence. A trivariate Cholesky decomposition estimated additive genetic (A), shared environment (C) and unique environment (E) contributions to the opportunity to use cannabis, the frequency of cannabis use, cannabis abuse/dependence, and the extent of overlap between genetic and environmental factors associated with each phenotype.
Variance components estimates were A = 0.64 [95% confidence interval (CI) 0.58–0.70] and E = 0.36 (95% CI 0.29–0.42) for age of opportunity to use cannabis, A = 0.74 (95% CI 0.66–0.80) and E = 0.26 (95% CI 0.20–0.34) for cannabis use frequency, and A = 0.78 (95% CI 0.65–0.88) and E = 0.22 (95% CI 0.12–0.35) for cannabis abuse/dependence. Opportunity shares 45% of genetic influences with the frequency of use, and only 17% of additive genetic influences are unique to abuse/dependence from those acting on opportunity and frequency.
There are significant genetic contributions to lifetime cannabis abuse/dependence, but a large proportion of this overlaps with influences acting on opportunity and frequency of use. Individuals without drug use opportunity are uninformative, and studies of drug use disorders must incorporate individual exposure to accurately identify aetiology.
Near IR total eclipse measurements have provided clear evidence during both 2nd and 3rd contacts for a limb extension of about 125 km for wavelengths in the range containing the CO fundamental vibration-rotation bands between 4.3 and 5.5 μm, when compared to the limb at nearby shorter wavelengths. This is interpreted as a “flash” spectrum in the CO lines, with the above extension representing the outer level of the CO emission layer. This height can be compared to the τCO = 1.0 level incorporated into recent representative atmospheric models (Ayres and Wiedemann, 1989) which is 90 km above the visible limb for a semi-empirical “hot chromosphere” model (Avrett, 1985) and 220 km for a “cool” radiative equilibrium model based upon work by Anderson (1989).
After neary 20 years since their discovery by Kosovichev and Zharkova, the mechanics of the release of seismic transients into the solar interior from some flares remain a mystery. Seismically emissive flares invariably show the signatures of intense chromosphere heating consistent with pressure variations sufficient to drive seismic transients commensurate with helioseismic observations—under certain conditions. Magnetic observations show the signatures of apparent magnetic changes, suggesting Lorentz-force transients that could likewise drive seismic transients—similarly subject to certain conditions. But, the diagnostic signatures of both of these prospective drivers are apparent over vast regions from which no significant seismic emission emanates. What distinguishes the source regions of transient seismic emission from the much vaster regions that show the signatures of both transient heating and magnetic variations but are acoustically unproductive? Observations of acoustically active flares in He II 304 Å by the Atomospheric Imaging Assembly (AIA) aboard the Solar Dynamics Observatory (SDO) offer a promising new resource with which to address this question.
Away-from-home foods have been shown to have lower nutritional quality and larger portion sizes than many foods prepared at home. We aimed to describe energy and nutrient intakes among 2–13-year-old Mexican children by eating location (at home and away from home), overall, by socio-economic status (SES) and by urbanicity.
Dietary intake was collected via one 24 h recall in the 2012 Mexican National Health and Nutrition Survey (ENSANUT). Location was reported for each food consumed. Results were adjusted for sex, day of recall, region, weight status, SES and urbanicity.
Mexico (nationally representative).
Children aged 2–5 years (n 1905) and 6–13 years (n 2868).
Children consumed the majority of daily energy at home (89% of 2–5-year-olds; 82 % of 6–13-year-olds). The most common away-from-home eating location was school (22 % of 2–5-year-olds; 43 % of 6–13-year-olds), followed by the street (14 % of 2–5-year-olds; 13 % of 6–13-year-olds). The most common foods consumed away from home were wheat/rice and corn mixed dishes, sugar-sweetened beverages, pastries/candy/desserts, milk (2–5-year-olds only) and salty snacks (6–13-year-olds). Multivariate models showed that high-SES 2–5-year-olds consumed 14 % of daily energy away from home v. 8 % among low-SES 2–5-year-olds, and high-SES 6–13-year-olds consumed 21 % of daily energy away from home v. 14 % among low-SES 6–13 year-olds. There were no differences by urban residence.
Among Mexican children, most foods and beverages were consumed at home. However, the percentage of foods consumed or purchased away from home increased with age and with SES.
Accurate data on the incidence of West Nile virus (WNV) disease are important for directing public health education and control activities. The objective of this project was to assess the underdiagnosis of WNV neuroinvasive disease through laboratory testing of patients with suspected viral meningitis or encephalitis at selected hospitals serving WNV-endemic regions in three states. Of the 279 patients with cerebrospinal fluid (CSF) specimens tested for WNV immunoglobulin M (IgM) antibodies, 258 (92%) were negative, 19 (7%) were positive, and two (1%) had equivocal results. Overall, 63% (12/19) of patients with WNV IgM-positive CSF had WNV IgM testing ordered by their attending physician. Seven (37%) cases would not have been identified as probable WNV infections without the further testing conducted through this project. These findings indicate that over a third of WNV infections in patients with clinically compatible neurological illness might be undiagnosed due to either lack of testing or inappropriate testing, leading to substantial underestimates of WNV neuroinvasive disease burden. Efforts should be made to educate healthcare providers and laboratorians about the local epidemiology of arboviral diseases and the optimal tests to be used in different clinical situations.
The development of solar acoustic holography over the past decade has opened a major new diagnostic avenue in local helioseismology (Lindsey & Braun 1990; 1997; 2000b). Its application to SOI-MDI data from SOHO has revealed “acoustic moats” surrounding sunspots, “acoustic glories” surrounding complex activeregions, and “acoustic condensations” suggesting the existence of significant seismic anomalies up to 20 Mm beneath active-region photospheres. It has given us the first seismic images of a solar flare, and has uncovered a remarkable anomaly in the statistical distribution of seismic emission from acoustic glories. A review of these and other accomplishments is given by Braun & Lindsey (2000a).
Computational seismic holography, applied to Solar Oscillations Investigation -Michelson Doppler Imager (SOI-MDI) data from SOHO, has recently given us the first images of an active region on the far side of the Sun(Lindsey & Braun 2000). The advent of phase-coherent seismic imaging is now allowing us quite literally to look into the solar interior from a local perspective, indeed to see through the solar interior acoustically to its far surface. Solar activity is critical to near-Earth space weather. A great deal of effort has been invested towards the prediction of flares and CMEs, based on the formidable presence of active regions on the near solar surface. Active regions can emerge rapidly from beneath the photosphere or appear on the east limb with relatively little warning. Because of this, the ability to anticipate the appearances of active regions will contribute substantially to forecasts of space weather on time scales of more than about a day. In collaboration with Dr. Phil Scherrer and the MDI team at Stanford University we are currently deriving far-side images from the lower resolution “medium-l” SOI-MDI Dopplergrams, which are obtained continuously through the year and arrive at MDI headquarters within 24 hours of their acquisition by the SOHO spacecraft. We are therefore already capable of locating large far-side active regions and predicting their appearance on the east solar limb to within a few hours more than a week in advance. In addition, ground-based networks such as GONG will soon have the capability for “real-time helioseismology”, and will be routinely monitoring the far surface of the Sun, and perhaps beneath the near surface, for emerging solar activity.
We designed a parent-directed home-visiting intervention targeting socioeconomic status (SES) disparities in children's early language environments. A randomized controlled trial was used to evaluate whether the intervention improved parents' knowledge of child language development and increased the amount and diversity of parent talk. Twenty-three mother–child dyads (12 experimental, 11 control, aged 1;5–3;0) participated in eight weekly hour-long home-visits. In the experimental group, but not the control group, parent knowledge of language development increased significantly one week and four months after the intervention. In lab-based observations, parent word types and tokens and child word types increased significantly one week, but not four months, post-intervention. In home-based observations, adult word tokens, conversational turn counts, and child vocalization counts increased significantly during the intervention, but not post-intervention. The results demonstrate the malleability of child-directed language behaviors and knowledge of child language development among low-SES parents.
This volume not only defines medievalism's margins, as well as its role in marginalizing other fields, ideas, people, places, and events, but also provides tools and models for exploring those issues and indicates new subjects to which they might apply. The eight opening essays address the physical marginalizing of medievalism in annotated texts on medieval studies; the marginalism of oneself via medievalism; medievalism's dearth of ecotheory and religious studies; academia's paucity of pop medievalism; and the marginalization of races, ethnicities, genders, sexual orientations, and literary characters in contemporary medievalism. The seven subsequent articles build on this foundation while discussing: the distancing of oneself (and others) during imaginary visits to the Middle Ages; lessons from the margins of Brazilian medievalism; mutual marginalization among factions of Spanish medieval studies; and medievalism in the marginalization of lower socio-economic classes in late-eighteenth- and early nineteenth-century Spain, of modern gamers, of contemporary laborers, and of Alfred Austin, a late-nineteenth- and early twentieth-century poet also known as Alfred the Little. In thus investigating the margins of and marginalization via medievalism, the volume affirms their centrality to the field. Karl Fugelso is Professor of Art History at Towson University in Baltimore, Maryland. Contributors: Nadia R. Altschul, Megan Arnott, Jaume Aurell, Juan Gomis Coloma, Elizabeth Emery, Vincent Ferré, Valerie B. Johnson, Alexander L. Kaufman, Erin Felicia Labbie, VickieLarsen, Kevin Moberly, Brent Moberly, Alicia C. Montoya, Serina Patterson, Jeff Rider, Lindsey Simon-Jones, Richard Utz, Helen Young.