Nontarget Effects of the Mosquito Adulticide Pyrethrin Applied Aerially During a West Nile Virus Outbreak in an Urban California Environment

In August 2006, a pyrethrin insecticide synergized with piperonyl butoxide (EverGreen Crop Protection EC 60-6, McLaughlin Gormley King Company, Golden Valley, MN) was sprayed in ultralow volumes over the city of Davis, CA, by the Sacramento-Yolo Mosquito and Vector Control District to control mosquitoes transmitting West Nile virus. Concurrently, we evaluated the impact of the insecticide on nontarget arthropods by 1) comparing mortality of treatment and control groups of sentinel arthropods, and 2) measuring the diversity and abundance of dead arthropods found on treatment and control tarps placed on the ground. We found no effect of spraying on nontarget sentinel species including dragonflies (Sympetrum corruptum), spiders (Argiope aurantia), butterflies (Colias eurytheme), and honeybees (Apis mellifera). In contrast, significantly higher diversity and numbers of nontarget arthropods were found on ground tarps placed in sprayed versus unsprayed areas. All of the dead nontarget species were small-bodied arthropods as opposed to the large-bodied sentinels that were not affected. The mortality of sentinel mosquitoes placed at the same sites as the nontarget sentinels and ground tarps ranged from 0% to 100%. Dead mosquitoes were not found on the ground tarps. We conclude that aerial spraying with pyrethrins had no impact on the large-bodied arthropods placed in the spray zone, but did have a measurable impact on a wide range of small-bodied organisms

Spatially resolved STIS spectra of WR+OB binaries with colliding winds

We present spatially resolved spectra of the visual WR+OB massive binaries WR86, WR146, and WR147, obtained with the Space Telescope Imaging Spectrograph on board the Hubble Space Telescope. The systems are classified as follows: WR86 = WC7 + B0 III, WR146 = WC6 + O8 I-IIf, WR147 = WN8 + O5-7 I-II(f). Both WR146 and WR147 are known to have strong non-thermal radio emission arising in a wind-wind collision shock zone between the WR and OB components. We find that the spectra of their O companions show Halpha profiles in emission, indicative of large mass-loss rates, and consistent with the colliding-wind model. Our spectra indicate that the B component in WR86 has a low mass-loss rate, which possibly explains the fact that WR86, despite being a long period WR+OB binary, was not found to be a strong non-thermal radio emitter. Because of the small mass-loss rate of the B star component in WR86, the wind collision region must be closer to the B star and smaller in effective area, hence generating smaller amounts of non-thermal radio emission. Absolute magnitudes for all the stars are estimated based on the spectral types of the components (based on the tables by Schmidt-Kaler for OB stars, and van der Hucht for WR stars), and compared with actual, observed magnitude differences. While the derived luminosities for the WC7 and B0 III stars in WR86 are consistent with the observed magnitude difference, we find a discrepancy of at least 1.5 magnitudes between the observed luminosities of the components in each of WR146 and WR147 and the absolute magnitudes expected from their spectral types. In both cases, it looks as though either the WR components are about 2 magnitudes too bright for their spectral types, or that the O components are about 2 magnitudes too faint. We discuss possible explanations for this apparent discrepancy.Comment: Accepted for publication in the Astronomical Journa

A Changing Wind Collision

We report on the first detection of a global change in the X-ray emitting properties of a wind–wind collision, thanks to XMM-Newton observations of the massive Small Magellenic Cloud (SMC) system HD 5980. While its light curve had remained unchanged between 2000 and 2005, the X-ray flux has now increased by a factor of ~2.5, and slightly hardened. The new observations also extend the observational coverage over the entire orbit, pinpointing the light-curve shape. It has not varied much despite the large overall brightening, and a tight correlation of fluxes with orbital separation is found without any hysteresis effect. Moreover, the absence of eclipses and of absorption effects related to orientation suggests a large size for the X-ray emitting region. Simple analytical models of the wind–wind collision, considering the varying wind properties of the eruptive component in HD 5980, are able to reproduce the recent hardening and the flux-separation relationship, at least qualitatively, but they predict a hardening at apastron and little change in mean flux, contrary to observations. The brightness change could then possibly be related to a recently theorized phenomenon linked to the varying strength of thin-shell instabilities in shocked wind regions

Percutaneous coronary angioplasty versus coronary artery bypass grafting in treatment of unprotected left main stenosis (NOBLE) : a prospective, randomised, open-label, non-inferiority trial

Background Coronary artery bypass grafting (CABG) is the standard treatment for revascularisation in patients with left main coronary artery disease, but use of percutaneous coronary intervention (PCI) for this indication is increasing. We aimed to compare PCI and CABG for treatment of left main coronary artery disease. Methods In this prospective, randomised, open-label, non-inferiority trial, patients with left main coronary artery disease were enrolled in 36 centres in northern Europe and randomised 1: 1 to treatment with PCI or CABG. Eligible patients had stable angina pectoris, unstable angina pectoris, or non-ST-elevation myocardial infarction. Exclusion criteria were ST-elevation myocardial infarction within 24 h, being considered too high risk for CABG or PCI, or expected survival of less than 1 year. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE), a composite of all-cause mortality, non-procedural myocardial infarction, any repeat coronary revascularisation, and stroke. Non-inferiority of PCI to CABG required the lower end of the 95% CI not to exceed a hazard ratio (HR) of 1 . 35 after up to 5 years of follow-up. The intention-to-treat principle was used in the analysis if not specified otherwise. This trial is registered with ClinicalTrials.gov identifier, number NCT01496651. Findings Between Dec 9, 2008, and Jan 21, 2015, 1201 patients were randomly assigned, 598 to PCI and 603 to CABG, and 592 in each group entered analysis by intention to treat. Kaplan-Meier 5 year estimates of MACCE were 29% for PCI (121 events) and 19% for CABG (81 events), HR 1 . 48 (95% CI 1 . 11-1 . 96), exceeding the limit for non-inferiority, and CABG was significantly better than PCI (p=0 . 0066). As-treated estimates were 28% versus 19% (1 . 55, 1 . 18-2 . 04, p= 0 . 0015). Comparing PCI with CABG, 5 year estimates were 12% versus 9% (1 . 07, 0 . 67-1 . 72, p= 0 . 77) for all-cause mortality, 7% versus 2% (2 . 88, 1 . 40-5 . 90, p= 0 . 0040) for non-procedural myocardial infarction, 16% versus 10% (1 . 50, 1 . 04-2 . 17, p= 0 . 032) for any revascularisation, and 5% versus 2% (2 . 25, 0 . 93-5 . 48, p= 0 . 073) for stroke. Interpretation The findings of this study suggest that CABG might be better than PCI for treatment of left main stem coronary artery disease.Peer reviewe

The unruptured intracranial aneurysm treatment score A multidisciplinary consensus

Objective: We endeavored to develop an unruptured intracranial aneurysm (UIA) treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in UIA management and research. Methods: An international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus. For internal (39 panel members involved in identification of relevant features) and external validation (30 independent external reviewers), 30 selected UIA cases were used to analyze agreement with UIATS management recommendations based on a 5-point Likert scale (5 indicating strong agreement). Interrater agreement (IRA) was assessed with standardized coefficients of dispersion (v(r)*) (v(r)* 5 0 indicating excellent agreement and v(r)* = 1 indicating poor agreement). Results: The UIATS accounts for 29 key factors in UIA management. Agreement with UIATS (mean Likert scores) was 4.2 (95% confidence interval [CI] 4.1-4.3) per reviewer for both reviewer cohorts; agreement per case was 4.3 (95% CI 4.1-4.4) for panel members and 4.5 (95% CI 4.3-4.6) for external reviewers (p = 0.017). Mean Likert scores were 4.2 (95% CI 4.1-4.3) for interventional reviewers (n = 56) and 4.1 (95% CI 3.9-4.4) for noninterventional reviewers (n = 12) (p = 0.290). Overall IRA (v(r)*) for both cohorts was 0.026 (95% CI 0.019-0.033). Conclusions: This novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty. Clinicians can use the UIATS as a comprehensive mechanism for indicating how a large group of specialists might manage an individual patient with a UIA.Peer reviewe

Statistical Analysis of the Processes Controlling Choline and Ethanolamine Glycerophospholipid Molecular Species Composition

The regulation and maintenance of the cellular lipidome through biosynthetic, remodeling, and catabolic mechanisms are critical for biological homeostasis during development, health and disease. These complex mechanisms control the architectures of lipid molecular species, which have diverse yet highly regulated fatty acid chains at both the sn1 and sn2 positions. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) serve as the predominant biophysical scaffolds in membranes, acting as reservoirs for potent lipid signals and regulating numerous enzymatic processes. Here we report the first rigorous computational dissection of the mechanisms influencing PC and PE molecular architectures from high-throughput shotgun lipidomic data. Using novel statistical approaches, we have analyzed multidimensional mass spectrometry-based shotgun lipidomic data from developmental mouse heart and mature mouse heart, lung, brain, and liver tissues. We show that in PC and PE, sn1 and sn2 positions are largely independent, though for low abundance species regulatory processes may interact with both the sn1 and sn2 chain simultaneously, leading to cooperative effects. Chains with similar biochemical properties appear to be remodeled similarly. We also see that sn2 positions are more regulated than sn1, and that PC exhibits stronger cooperative effects than PE. A key aspect of our work is a novel statistically rigorous approach to determine cooperativity based on a modified Fisher's exact test using Markov Chain Monte Carlo sampling. This computational approach provides a novel tool for developing mechanistic insight into lipidomic regulation

European consensus conference on unruptured brain AVMs treatment (Supported by EANS, ESMINT, EGKS, and SINCH)

In December of 2016, a Consensus Conference on unruptured AVM treatment, involving 24 members of the three European societies dealing with the treatment of cerebral AVMs (EANS, ESMINT, and EGKS) was held in Milan, Italy. The panel made the following statements and general recommendations: (1) Brain arteriovenous malformation (AVM) is a complex disease associated with potentially severe natural history; (2) The results of a randomized trial (ARUBA) cannot be applied equally for all unruptured brain arteriovenous malformation (uBAVM) and for all treatment modalities; (3) Considering the multiple treatment modalities available, patients with uBAVMs should be evaluated by an interdisciplinary neurovascular team consisting of neurosurgeons, neurointerventionalists, radiosurgeons, and neurologists experienced in the diagnosis and treatment of brain AVM; (4) Balancing the risk of hemorrhage and the associated restrictions of everyday activities related to untreated unruptured AVMs against the risk of treatment, there are sufficient indications to treat unruptured AVMs grade 1 and 2 (Spetzler-Martin); (5) There may be indications for treating patients with higher grades, based on a case-to-case consensus decision of the experienced team; (6) If treatment is indicated, the primary strategy should be defined by the multidisciplinary team prior to the beginning of the treatment and should aim at complete eradication of the uBAVM; (7) After having considered the pros and cons of a randomized trial vs. a registry, the panel proposed a prospective European Multidisciplinary Registry.Peer reviewe

Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease

STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti-IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder

Procedural Volume and Outcomes With Radial or Femoral Access for Coronary Angiography and Intervention

ObjectivesThe study sought to evaluate the relationship between procedural volume and outcomes with radial and femoral approach.BackgroundRIVAL (RadIal Vs. femorAL) was a randomized trial of radial versus femoral access for coronary angiography/intervention (N = 7,021), which overall did not show a difference in primary outcome of death, myocardial infarction, stroke, or non–coronary artery bypass graft major bleeding.MethodsIn pre-specified subgroup analyses, the hazard ratios for the primary outcome were compared among centers divided by tertiles and among individual operators. A multivariable Cox proportional hazards model was used to determine the independent effect of center and operator volumes after adjusting for other variables.ResultsIn high-volume radial centers, the primary outcome was reduced with radial versus femoral access (hazard ratio [HR]: 0.49; 95% confidence interval [CI]: 0.28 to 0.87) but not in intermediate- (HR: 1.23; 95% CI: 0.88 to 1.72) or low-volume centers (HR: 0.83; 95% CI: 0.52 to 1.31; interaction p = 0.021). High-volume centers enrolled a higher proportion of ST-segment elevation myocardial infarction (STEMI). After adjustment for STEMI, the benefit of radial access persisted at high-volume radial centers. There was no difference in the primary outcome between radial and femoral access by operator volume: high-volume operators (HR: 0.79; 95% CI: 0.48 to 1.28), intermediate (HR: 0.87; 95% CI: 0.60 to 1.27), and low (HR: 1.10; 95% CI: 0.74 to 1.65; interaction p = 0.536). However, in a multivariable model, overall center volume and radial center volume were independently associated with the primary outcome but not femoral center volume (overall percutaneous coronary intervention volume HR: 0.92, 95% CI: 0.88 to 0.96; radial volume HR: 0.88, 95% CI: 0.80 to 0.97; and femoral volume HR: 1.00, 95% CI: 0.94 to 1.07; p = 0.98).ConclusionsProcedural volume and expertise are important, particularly for radial percutaneous coronary intervention. (A Trial of Trans-radial Versus Trans-femoral Percutaneous Coronary Intervention [PCI] Access Site Approach in Patients With Unstable Angina or Myocardial Infarction Managed With an Invasive Strategy [RIVAL]; NCT01014273