434 research outputs found

    Line intensity enhancements in stellar coronal X-ray spectra due to opacity effects

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    Context. The I(15.01 A)/I(16.78 A) emission line intensity ratio in Fe XVII has been reported to deviate from its theoretical value in solar and stellar X-ray spectra. This is attributed to opacity in the 15.01 A line, leading to a reduction in its intensity, and was interpreted in terms of a geometry in which the emitters and absorbers are spatially distinct. Aims. We study the I(15.01 A)/I(16.78 A) intensity ratio for the active cool dwarf EV Lac, in both flare and quiescent spectra. Methods. The observations were obtained with the Reflection Grating Spectrometer on the XMM-Newton satellite. The emission measure distribution versus temperature reconstruction technique is used for our analysis. Results. We find that the 15.01 A line exhibits a significant enhancement in intensity over the optically thin value. To our knowledge, this is the first time that such an enhancement has been detected on such a sound statistical basis. We interpret this enhancement in terms of a geometry in which the emitters and absorbers are not spatially distinct, and where the geometry is such that resonant pumping of the upper level has a greater effect on the observed line intensity than resonant absorption in the line-of-sight.Comment: accepted for publication in A&

    The Patterns of High-Level Magnetic Activity Occurring on the Surface of V1285 Aql: The OPEA Model of Flares and DFT Models of Stellar Spots

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    Statistically analyzing Johnson UBVR observations of V1285 Aql during the three observing seasons, both activity level and behavior of the star are discussed in respect to obtained results. We also discuss the out-of-flare variation due to rotational modulation. Eighty-three flares were detected in the U-band observations of season 2006 . First, depending on statistical analyses using the independent samples t-test, the flares were divided into two classes as the fast and the slow flares. According to the results of the test, there is a difference of about 73 s between the flare-equivalent durations of slow and fast flares. The difference should be the difference mentioned in the theoretical models. Second, using the one-phase exponential association function, the distribution of the flare-equivalent durations versus the flare total durations was modeled. Analyzing the model, some parameters such as plateau, half-life values, mean average of the flare-equivalent durations, maximum flare rise, and total duration times are derived. The plateau value, which is an indicator of the saturation level of white-light flares, was derived as 2.421{\pm}0.058 s in this model, while half-life is computed as 201 s. Analyses showed that observed maximum value of flare total duration is 4641 s, while observed maximum flare rise time is 1817 s. According to these results, although computed energies of the flares occurring on the surface of V1285 Aql are generally lower than those of other stars, the length of its flaring loop can be higher than those of more active stars.Comment: 44 pages, 10 figures, 5 tables, 2011PASP..123..659

    Contrôle et lutte contre la fraude du patient européen

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    Il est des chiffres qui donnent le vertige. Incontestablement, ceux concernant les pertes dues à la fraude et la corruption en matière de soins en font partie. Certaines estimations font en effet état de 56 milliards d'euros perdus annuellement en Europe, ce qui représente près de 80 millions de perte chaque jour et plus de 5% de l'ensemble des budgets nationaux consacrés à la santé (Gee et alii, 2010)

    Incorporating dose effects in network meta-analysis

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    Systematic reviews with network meta-analysis that ignore potential dose effects could limit the applicability and validity of review findings. This article aims to help content experts (eg, clinicians), methodologists, and statisticians better understand how to incorporate dose effects in network meta-analysis. Three models are described that make different clinical and statistical assumptions about how to model dose effects. This article also illustrates the importance of dose effects in understanding the potential risk of harm in people with dementia from cerebrovascular events associated with atypical antipsychotic drug use (quetiapine, olanzapine, and risperidone) and the potential risk of harm in people with nausea and headache associated with cholinesterase inhibitor use (donepezil, galantamine, and rivastigmine). Finally, important considerations when choosing between different network meta-analysis models incorporating dose effects are discussed

    Blood Biomarkers and Metabolomic Profiling for the Early Diagnosis of Vancomycin-Associated Acute Kidney Injury: A Systematic Review and Meta-Analysis of Experimental Studies

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    Background: several blood-based biomarkers have been proposed for predicting vancomycin-associated kidney injury (VIKI). However, no systematic analysis has compared their prognostic value. Objective: this systematic review and meta-analysis was designed to investigate the role of blood biomarkers and metabolomic profiling as diagnostic and prognostic predictors in pre-clinical studies of VIKI. Methods: a systematic search of PubMed was conducted for relevant articles from January 2000 to May 2022. Animal studies that administered vancomycin and studied VIKI were eligible for inclusion. Clinical studies, reviews, and non-English literature were excluded. The primary outcome was to investigate the relationship between the extent of VIKI as measured by blood biomarkers and metabolomic profiling. Risk of bias was assessed with the CAMARADES checklist the SYRCLE's risk of bias tool. Standard meta-analysis methods (random-effects models) were used. Results: there were four studies for the same species, dosage, duration of vancomycin administration and measurement only for serum creatine and blood urea nitrogen in rats. A statistically significant increase was observed between serum creatinine in the vancomycin group compared to controls (pooled p = 0.037; Standardized Mean Difference: 2.93; 95% CI: 0.17 to 5.69; I-2 = 92.11%). Serum BUN levels were not significantly different between control and vancomycin groups (pooled p = 0.11; SMD: 3.05; 95% CI: 0.69 to 6.8; I-2 = 94.84%). We did not identify experimental studies using metabolomic analyses in animals with VIKI. Conclusions: a total of four studies in rodents only described outcomes of kidney injury as defined by blood biomarkers. Blood biomarkers represented included serum creatinine and BUN. Novel blood biomarkers have not been explored

    SMART: Unique splitting-while-merging framework for gene clustering

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    Copyright @ 2014 Fa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Successful clustering algorithms are highly dependent on parameter settings. The clustering performance degrades significantly unless parameters are properly set, and yet, it is difficult to set these parameters a priori. To address this issue, in this paper, we propose a unique splitting-while-merging clustering framework, named “splitting merging awareness tactics” (SMART), which does not require any a priori knowledge of either the number of clusters or even the possible range of this number. Unlike existing self-splitting algorithms, which over-cluster the dataset to a large number of clusters and then merge some similar clusters, our framework has the ability to split and merge clusters automatically during the process and produces the the most reliable clustering results, by intrinsically integrating many clustering techniques and tasks. The SMART framework is implemented with two distinct clustering paradigms in two algorithms: competitive learning and finite mixture model. Nevertheless, within the proposed SMART framework, many other algorithms can be derived for different clustering paradigms. The minimum message length algorithm is integrated into the framework as the clustering selection criterion. The usefulness of the SMART framework and its algorithms is tested in demonstration datasets and simulated gene expression datasets. Moreover, two real microarray gene expression datasets are studied using this approach. Based on the performance of many metrics, all numerical results show that SMART is superior to compared existing self-splitting algorithms and traditional algorithms. Three main properties of the proposed SMART framework are summarized as: (1) needing no parameters dependent on the respective dataset or a priori knowledge about the datasets, (2) extendible to many different applications, (3) offering superior performance compared with counterpart algorithms.National Institute for Health Researc

    Multi-insecticide resistant malaria vectors in the field remain susceptible to malathion, despite the presence of Ace1 point mutations

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    Insecticide resistance in Anopheles mosquitoes is seriously threatening the success of insecticide-based malaria vector control. Surveillance of insecticide resistance in mosquito populations and identifying the underlying mechanisms enables optimisation of vector control strategies. Here, we investigated the molecular mechanisms of insecticide resistance in three Anopheles coluzzii field populations from southern Cote d'Ivoire, including Agboville, Dabou and Tiassale. All three populations were resistant to bendiocarb, deltamethrin and DDT, but not or only very weakly resistant to malathion. The absence of malathion resistance is an unexpected result because we found the acetylcholinesterase mutation Ace1-G280S at high frequencies, which would typically confer cross-resistance to carbamates and organophosphates, including malathion. Notably, Tiassale was the most susceptible population to malathion while being the most resistant one to the pyrethroid deltamethrin. The resistance ratio to deltamethrin between Tiassale and the laboratory reference colony was 1,800 fold. By sequencing the transcriptome of individual mosquitoes, we found numerous cytochrome P450-dependent monooxygenases - including CYP6M2, CYP6P2, CYP6P3, CYP6P4 and CYP6P5 - overexpressed in all three field populations. This could be an indication for negative cross-resistance caused by overexpression of pyrethroid-detoxifying cytochrome P450s that may activate pro-insecticides, thereby increasing malathion susceptibility. In addition to the P450s, we found several overexpressed carboxylesterases, glutathione S-transferases and other candidates putatively involved in insecticide resistance

    A systematic re-examination of processing of MHCI-bound antigenic peptide precursors by ER aminopeptidase 1

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    Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims antigenic peptide precursors to generate mature antigenic peptides for presentation by major histocompatibility complex class I (MHCI) molecules and regulates adaptive immune responses. ERAP1 has been proposed to trim peptide precursors both in solution and in pre-formed MHCI-peptide complexes, but which mode is more relevant to its biological function remains controversial. Here, we compared ERAP1-mediated trimming of antigenic peptide precursors in solution or when bound to three MHCI alleles, HLA-B*58, HLA-B*08 and HLA-A*02. For all MHCI-peptide combinations, peptide binding onto MHCI protected against ERAP1-mediated trimming. In only a single MHCI-peptide combination, trimming of an HLA-B*08-bound 12mer progressed at a considerable rate, albeit still slower than in solution. Results from thermodynamic, kinetic and computational analyses suggested that this 12mer is highly labile and that apparent on-MHC trimming rates are always slower than that of MHCI-peptide dissociation. Both ERAP2 and leucine aminopeptidase, an enzyme unrelated to antigen processing, could trim this labile peptide from pre-formed MHCI complexes as efficiently as ERAP1. A pseudopeptide analogue with high affinity for both HLA-B*08 and the ERAP1 active site could not promote the formation of a ternary ERAP1-MHCI-peptide complex. Similarly, no interactions between ERAP1 and purified peptide loading complex (PLC) were detected in the absence or presence of a pseudopeptide trap. We conclude that MHCI binding protects peptides from ERAP1 degradation and that trimming in solution, along with the dynamic nature of peptide binding to MHCI, are sufficient to explain ERAP1 processing of antigenic peptide precursors

    VectorDisk: a microfluidic platform integrating diagnostic markers for evidence-based mosquito control

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    Effective mosquito monitoring relies on the accurate identification and characterization of the target population. Since this process requires specialist knowledge and equipment that is not widely available, automated field-deployable systems are highly desirable. We present a centrifugal microfluidic cartridge, the VectorDisk, which integrates TaqMan PCR assays in two feasibility studies, aiming to assess multiplexing capability, specificity, and reproducibility in detecting disk-integrated vector-related assays. In the first study, pools of 10 mosquitoes were used as samples. We tested 18 disks with 27 DNA and RNA assays each, using a combination of multiple microfluidic chambers and detection wavelengths (geometric and color multiplexing) to identify mosquito and malaria parasite species as well as insecticide resistance mechanisms. In the second study, purified nucleic acids served as samples to test arboviral and malaria infective mosquito assays. Nine disks were tested with 14 assays each. No false positive results were detected on any of the disks. The coe cient of variation in reproducibility tests was <10%. The modular nature of the platform, the easy adaptation of the primer/probe panels, the cold chain independence, the rapid (2-3 h) analysis, and the assay multiplexing capacity are key features, rendering the VectorDisk a potential candidate for automated vector analysis
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