Enterovirus D68 (EV‐D68) is an emerging infection associated with acute flaccid myelitis (AFM). Cases of AFM associated with EV‐D68 infection have increased in recent years and the evidence for a ...causal link is growing. However, our understanding of the epidemiology, clinical features, prognosis, and neurological sequelae of EV‐D68 requires ongoing surveillance and investigation. We report five cases of AFM in previously typically developing children (2–6y) from South East Scotland during September and October 2016 after infection with EV‐D68 (all detected in the nasopharyngeal aspirates). All cases presented with significant neurological symptoms, which were severe in two cases requiring intensive care support because of respiratory paralysis. At 18‐month follow‐up, two cases remain ventilator‐dependent with other cases requiring ongoing community rehabilitation. These cases represent one of the largest reported paediatric cluster of AFM associated with EV‐D68 in Europe. The epidemiology and clinical information add to the knowledge base and the 18‐month outcome will help clinicians to counsel families.
What this paper adds
Nasopharyngeal aspirate is more sensitive for viral isolation and isolated in all cases.
Clinical outcome at 18 months after enterovirus D68 with acute flaccid myelitis provides information on extent of recovery and level of disability.
Resumen
Resultado de la mielitis flácida aguda pediátrica asociada con enterovirus D68 (EV‐D68): una serie de casos
El enterovirus D68 (EV‐D68) es una infección emergente asociada con mielitis flácida aguda (MFA). Los casos de MFA asociados con la infección por EV‐D68 han aumentado en los últimos años y la evidencia de un vínculo causal está creciendo. Sin embargo, nuestra comprensión de la epidemiología, las características clínicas, el pronóstico y las secuelas neurológicas del EV‐D68 requiere una vigilancia e investigación continuas. Presentamos cinco casos de MFA en niños con desarrollo típico (2 a 6 años) del sureste de Escocia durante septiembre y octubre de 2016 después de la infección con EV‐D68 (todos detectados en los aspirados nasofaríngeos). Todos los casos presentaron síntomas neurológicos significativos, que fueron graves en dos casos que requirieron apoyo de cuidados intensivos debido a la parálisis respiratoria. A los 18 meses de seguimiento, dos casos siguen siendo dependientes del ventilador, mientras que otros casos requieren una rehabilitación continua de la comunidad. Estos casos representan uno de los grupos pediátricos más grandes de MFA asociados con EV‐D68 en Europa. La epidemiología y la información clínica se suman a la base de conocimientos y el resultado de 18 meses ayudará a los clínicos a asesorar a las familias.
Resumen
Resultado da mielite aguda flácida pediátrica associada com enterovirus D68 (EV‐D68): uma série de casos
O Enterovírus D68 (EV‐D68) é uma infecção emergente associada com mielite aguda flácida (MAF). Casos de MAF associados com infecção por EV‐D68 aumentaram nos últimos anos, e a evidência para uma relação causal tem crescido. No entanto, nossa compreensão sobre a epidemiologia, aspectos clínicos, prognóstico e sequelas neurológicas do EV‐D68 requer contínuo monitoramento e investigação. Relatamos cinco casos de MAF em crianças que previamente apresentavam desenvolvimento típico (2‐6 a), do sudeste da Escócia durante setembro e outubro de 2016 após infecção com EV‐D68 (todos detectados por aspiração nasofaríngea). Todos os casos apresentaram sintomas neurológicos significativos, que eram severos em dois casos, requerendo cuidados intensivos por causa de paralisia respiratória. No acompanhamento de 18 meses, dois casos permaneceram dependents de ventilador, com outros casos requerendo reabilitação continua na comunidade. Estes casos representam um dos maiores grupos pediátricos de MAF associada a EV‐D68 na Europa. A epidemiologia e informação clínica acrescentam para a base de conhecimento, e o resultado em 18 meses ajudará clínicos a aconselhar as famílias.
What this paper adds
Nasopharyngeal aspirate is more sensitive for viral isolation and isolated in all cases.
Clinical outcome at 18 months after enterovirus D68 with acute flaccid myelitis provides information on extent of recovery and level of disability.
This article is commented on by Okumura and Mori on pages 290–291 of this issue.
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Abstract
Clouds are prevalent in many of the exoplanet atmospheres that have been observed to date. For transiting exoplanets, we know if clouds are present because they mute spectral features and ...cause wavelength-dependent scattering. While the exact composition of these clouds is largely unknown, this information is vital to understanding the chemistry and energy budget of planetary atmospheres. In this work, we observe one transit of the hot Jupiter WASP-17b with JWST’s Mid-Infrared Instrument Low Resolution Spectrometer and generate a transmission spectrum from 5 to 12
μ
m. These wavelengths allow us to probe absorption due to the vibrational modes of various predicted cloud species. Our transmission spectrum shows additional opacity centered at 8.6
μ
m, and detailed atmospheric modeling and retrievals identify this feature as SiO
2
(s) (quartz) clouds. The SiO
2
(s) clouds model is preferred at 3.5–4.2
σ
versus a cloud-free model and at 2.6
σ
versus a generic aerosol prescription. We find the SiO
2
(s) clouds are composed of small ∼0.01
μ
m particles, which extend to high altitudes in the atmosphere. The atmosphere also shows a depletion of H
2
O, a finding consistent with the formation of high-temperature aerosols from oxygen-rich species. This work is part of a series of studies by our JWST Telescope Scientist Team (JWST-TST), in which we will use Guaranteed Time Observations to perform Deep Reconnaissance of Exoplanet Atmospheres through Multi-instrument Spectroscopy (DREAMS).
Increasing social connection and access to care has been found to decrease the rate of suicide in U.S. veterans. The Veteran Outreach Into the Community to Expand Social Support (VOICES) is an ...intervention developed by Department Veteran Affairs (VA) staff to improve social connection and provide information about services by implementing community-based Veterans Socials. Seventy veterans at eight locations completed an anonymous cross-sectional survey. This evaluation examined three domains,
acceptability
(i.e., perceived value),
demand
(i.e., estimated or actual use), and
expansion
(i.e., sustainability and increase of Veterans Socials across time and locations). Findings indicated considerable levels of acceptability, demand for, and expansion of this intervention. Additionally, data suggested this intervention may increase social connection and utilization of VA services among attendees.
Genotyping for CYP2C19 no function alleles to guide antiplatelet therapy after percutaneous coronary intervention (PCI) improves clinical outcomes. Although results for the increased function ...CYP2C19*17 allele are also reported, its clinical relevance in this setting remains unclear. A collaboration across nine sites examined antiplatelet therapy prescribing and clinical outcomes in 3,342 patients after implementation of CYP2C19‐guided antiplatelet therapy. Risk of major atherothrombotic and bleeding events over 12 months after PCI were compared across cytochrome P450 2C19 isozyme (CYP2C19) metabolizer phenotype and antiplatelet therapy groups by proportional hazards regression. Clopidogrel was prescribed to a similar proportion of CYP2C19 normal (84.5%), rapid (82.9%), and ultrarapid metabolizers (80.6%) (P = 0.360). Clopidogrel‐treated normal metabolizers (20.4 events/100 patient‐years; adjusted hazard ratio (HR) 1.00, 95% confidence interval (CI), 0.75–1.33, P = 0.993) and clopidogrel‐treated rapid or ultrarapid metabolizers (19.1 events/100 patient‐years; adjusted HR 0.95, 95% CI, 0.69–1.30, P = 0.734) exhibited no difference in major atherothrombotic events compared with patients treated with prasugrel or ticagrelor (17.6 events/100 patient‐years). In contrast, clopidogrel‐treated intermediate and poor metabolizers exhibited significantly higher atherothrombotic event risk compared with prasugrel/ticagrelor‐treated patients (adjusted HR 1.56, 95% CI, 1.12–2.16, P = 0.008). When comparing clopidogrel‐treated rapid or ultrarapid metabolizers to normal metabolizers, no difference in atherothrombotic (adjusted HR 0.97, 95% CI, 0.73–1.29, P = 0.808) or bleeding events (adjusted HR 1.34, 95% CI, 0.83–2.17, P = 0.224) were observed. In a real‐world setting of genotype‐guided antiplatelet therapy, the CYP2C19*17 allele did not significantly impact post‐PCI prescribing decisions or clinical outcomes. These results suggest the CYP2C19 *1/*17 and *17/*17 genotypes have limited clinical utility to guide antiplatelet therapy after PCI.
A high rate of malfunction, predominantly intermittent high-frequency artifacts (HFAs), has been recently reported in Abbott Medical Tendril pacing leads.
To investigate the factors associated with ...the occurrence of HFAs on Tendril leads using a commonly used comparator lead for a control.
We reviewed institutional data for Medtronic CapSureFix 5076 and Abbott Medical Tendril pace-sense leads retrospectively. Recordings deemed to be due to electromagnetic interference and far-field oversensing were not included in the classification of HFAs.
A total of 7673 leads were analyzed: 1628 Optim-insulated Tendril leads, 825 non-Optim Tendril leads, and 5220 CapSureFix 5076. HFAs were seen in 212 leads and were more frequently observed in Tendril compared to CapSureFix leads during a mean follow-up of 4.1 ± 3.6 years. Lower age at implant, defibrillator systems, atrial position, and connection to an Abbott Medical generator were associated with increased HFA. In multivariable analysis, only connection to Abbott Medical generators (odds ratio 7.686, P < .001) and age (odds ratio 0.988 per year, P = .016) were independently associated with HFAs on pace-sense leads. In an Abbott-generator-only analysis, Optim-insulated Tendril leads were more likely to display HFAs than non-Optim Tendril leads but not Medtronic CapSureFix 5076 leads.
Abbott Medical pulse generators independently predict HFA in Tendril and CapSureFix 5076 leads, likely the result of displaying short or low-amplitude noise episodes that other devices do not record. When restricted to Abbott generators only, Optim-insulated Tendril leads show an increased incidence of HFAs when compared to non-Optim Tendril leads but not CapSureFix 5076 leads.
Retrospective studies show improved outcomes in colorectal cancer patients if taking statins, including overall survival, pathological response of rectal cancer to preoperative chemoradiotherapy ...(pCRT), and reduced acute and late toxicities of pelvic radiation. Major tumour regression following pCRT has strong prognostic significance and can be assessed in vivo using MRI-based tumour regression grading (mrTRG) or after surgery using pathological TRG (pathTRG).
A double-blind phase 2 trial will randomise 222 patients planned to receive long-course fluoropyrimidine-based pCRT for rectal adenocarcinoma at 18+ sites in New Zealand and Australia. Patients will receive simvastatin 40 mg or placebo daily for 90 days starting 1 week prior to standard pCRT. Pelvic MRI 6 weeks after pCRT will assess mrTRG grading prior to surgery. The primary objective is rates of favourable (grades 1-2) mrTRG following pCRT with simvastatin compared to placebo, considering mrTRG in 4 ordered categories (1, 2, 3, 4-5). Secondary objectives include comparison of: rates of favourable pathTRG in resected tumours; incidence of toxicity; compliance with intended pCRT and trial medication; proportion of patients undergoing surgical resection; cancer outcomes and pathological scores for radiation colitis. Tertiary objectives include: association between mrTRG and pathTRG grouping; inter-observer agreement on mrTRG scoring and pathTRG scoring; studies of T-cell infiltrates in diagnostic biopsies and irradiated resected normal and malignant tissue; and the effect of simvastatin on markers of systemic inflammation (modified Glasgow prognostic score and the neutrophil-lymphocyte ratio). Trial recruitment commenced April 2018.
When completed this study will be able to observe meaningful differences in measurable tumour outcome parameters and/or toxicity from simvastatin. A positive result will require a larger RCT to confirm and validate the merit of statins in the preoperative management of rectal cancer. Such a finding could also lead to studies of statins in conjunction with chemoradiation in a range of other malignancies, as well as further exploration of possible mechanisms of action and interaction of statins with both radiation and chemotherapy. The translational substudies undertaken with this trial will provisionally explore some of these possible mechanisms, and the tissue and data can be made available for further investigations.
ANZ Clinical Trials Register ACTRN12617001087347. (www.anzctr.org.au, registered 26/7/2017) Protocol Version: 1.1 (June 2017).
Soybean (Glycinemax) is a hugely valuable soft commodity that generates tens of billions of dollars annually. This value is due in part to the balanced composition of the seed which is roughly 1:2:2 ...oil, starch, and protein by weight. In turn, the seeds have many uses with various derivatives appearing broadly in processed food products. As is true with many edible seeds, soybeans contain proteins that are anti-nutritional factors and allergens. Soybean, along with milk, eggs, fish, crustacean shellfish, tree nuts, peanuts, and wheat, elicit a majority of food allergy reactions in the United States. Soybean seed composition can be affected by breeding, and environmental conditions (e.g., temperature, moisture, insect/pathogen load, and/or soil nutrient levels). The objective of this study was to evaluate the influence of genotype and environment on allergen and anti-nutritional proteins in soybean. To address genetic and environmental effects, four varieties of non-GM soybeans were grown in six geographically distinct regions of North America (Georgia, Iowa, Kansas, Nebraska, Ontario, and Pennsylvania). Absolute quantification of proteins by mass spectrometry can be achieved with a technique called multiple reaction monitoring (MRM), during which signals from an endogenous protein are compared to those from a synthetic heavy-labeled internal standard. Using MRM, eight allergens were absolutely quantified for each variety in each environment. Statistical analyses show that for most allergens, the effects of environment far outweigh the differences between varieties brought about by breeding.
Plant seeds provide a significant portion of the protein present in the human diet, but are also the major contributors of allergenic proteins that cause a majority of the reported cases of ...food-induced anaphylaxis. New varieties of grains and nuts as well as other seeds could be screened for allergen content before they are introduced as cultivars for food production using mass spectrometry-based quantitation approaches. Here, we present a practical comparison of gel-free and label-free methods, peak integration and spectral counting, using a linear trap mass spectrometer. The results show that both methods are linear and reproducible with protein standards from 5–200 ng, however, bioinformatic analysis for spectral counting is much simpler and therefore more amenable to high-throughput sample processing. We therefore applied spectral counting towards the analysis of transgenic peanut lines targeting the reduction of a prominent allergen. Spectral count analysis of an Ara h 2 (conglutin-7) RNA-silenced line confirmed reduction of this allergen as well as Ara h 6 (conglutin), which was further confirmed by quantitative immunoblotting. Other collateral changes include an increase in Ara h 10 (oleosin 1) in one of the three lines, a decrease in conarachin as well as increased 13-lipoxygenase and Ahy-3 (arachin) in two of three lines.
Black patients suffer worse outcomes after percutaneous coronary intervention (PCI) than White patients. Inequities in antiplatelet prescribing may contribute to this health disparity. We compared ...P2Y
inhibitor prescribing by race following CYP2C19 genotyping to guide antiplatelet therapy selection after PCI. Patients from 9 sites that performed clinical CYP2C19 genotyping after PCI were included. Alternative therapy (e.g., prasugrel or ticagrelor) was recommended for CYP2C19 no-function allele carriers, in whom clopidogrel is predicted to be less effective. The primary outcome was choice of P2Y
inhibitor (clopidogrel vs. alternative therapy) based on genotype. Of 3,342 patients included, 2,448 (73%) were White, and 659 (20%) were Black. More Black than White patients had a no-function allele (34.3% vs. 29.7%, P = 0.024). At hospital discharge following PCI, 44.2% of Black and 44.0% of White no-function allele carriers were prescribed alternative therapy. At the time of the last follow-up within 12 months, numerically fewer Black (51.8%) than White (56.7%) no-function allele carriers were prescribed alternative therapy (P = 0.190). However, the difference was not significant after accounting for other factors associated with P2Y
inhibitor selection (odds ratio 0.79, 95% confidence interval 0.58-1.08). Alternative therapy use did not differ between Black (14.3%) and White (16.7%) patients without a no-function allele (P = 0.232). Among real-world patients who received CYP2C19 testing after PCI, P2Y
inhibitor prescribing rates did not differ between Black and White patients. Our data suggest an absence of racial disparity in genotype-guided antiplatelet prescribing among patients receiving CYP2C19 testing.
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