Why Is There a Lack of Consensus on Molecular Subgroups of Glioblastoma? Understanding the Nature of Biological and Statistical Variability in Glioblastoma Expression Data

Gene expression patterns characterizing clinically-relevant molecular subgroups of glioblastoma are difficult to reproduce. We suspect a combination of biological and analytic factors confounds interpretation of glioblastoma expression data. We seek to clarify the nature and relative contributions of these factors, to focus additional investigations, and to improve the accuracy and consistency of translational glioblastoma analyses.We analyzed gene expression and clinical data for 340 glioblastomas in The Cancer Genome Atlas (TCGA). We developed a logic model to analyze potential sources of biological, technical, and analytic variability and used standard linear classifiers and linear dimensional reduction algorithms to investigate the nature and relative contributions of each factor.Commonly-described sources of classification error, including individual sample characteristics, batch effects, and analytic and technical noise make measurable but proportionally minor contributions to inconsistent molecular classification. Our analysis suggests that three, previously underappreciated factors may account for a larger fraction of classification errors: inherent non-linear/non-orthogonal relationships among the genes used in conjunction with classification algorithms that assume linearity; skewed data distributions assumed to be Gaussian; and biologic variability (noise) among tumors, of which we propose three types.Our analysis of the TCGA data demonstrates a contributory role for technical factors in molecular classification inconsistencies in glioblastoma but also suggests that biological variability, abnormal data distribution, and non-linear relationships among genes may be responsible for a proportionally larger component of classification error. These findings may have important implications for both glioblastoma research and for translational application of other large-volume biological databases

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Comparison of Pasteur and Behringwerke antivenoms in envenoming by the carpet viper (Echis carinatus).

Bites and envenoming by the carpet viper Echis carinatus are common medical emergencies in parts of Nigeria, but the most effective use of the various commercially produced antivenoms in treatment has not been established. Pasteur Paris Echis monospecific and Behringwerke West and North Africa Bitis-Echis-Naja polyspecific antivenoms were compared in two groups of seven patients with incoagulable blood after E carinatus bites. In both groups spontaneous bleeding stopped within a few hours and local swelling subsided within two weeks after the initial antivenom injection. Pasteur antivenom (20-40 ml) restored blood coagulability within 12 hours in all cases, but 60--180 ml of Behringwerke antivenom was effective in only four cases. Persisting venom procoagulant activity was observed in the remaining three cases. Despite its potency in the mouse protection test, Behringwerke antivenom is unreliable and unpredictable in neutralising venom procoagulant in humans bitten by E carinatus

Multiplex TaqMan qPCR assay for specific identification of encapsulated Trichinella species prevalent in North America

BACKGROUND Human trichinellosis is a foodborne parasitic zoonotic disease caused by ingestion of raw or undercooked meat infected with nematode larvae of the genus Trichinella. In the USA, sporadic cases and outbreaks caused by the consumption of wild game meat infected with Trichinella have been reported. The current methods for diagnosis such as serology and microscopy are not specific, may result in false negative results, and cannot differentiate encapsulated Trichinella larvae to species level. The molecular protocols currently available for the differentiation of all encapsulate Trichinella species prevalent in North America have some limitations such as the inability to identify and resolve the presence of several Trichinella species in a single test. OBJECTIVES/METHODS In this study we developed and evaluated a multiplex TaqMan quantitative real-time polymerase chain reaction (qPCR) assay, which can simultaneously detect, identify and differentiate all species of encapsulated Trichinella occurring in North America i.e., T. nativa, T. spiralis, T. murrelli and Trichinella T6, even in cases of multiple infection in a single sample. We investigated two human biopsies and 35 wild animal meat samples considered as having a high likelihood of harboring Trichinella larvae obtained from the United States during 2009-2017. FINDINGS Using the multiplex assay describe here, 22 (59%) samples that tested positive contained Trichinella spp., were identified as: T. nativa (n = 7, including a human biopsy), T. spiralis (n = 9, including a human biopsy), T. murrelli (n = 3), Trichinella T6 (n = 1). Results also included two rare mixed infection cases in bears, a T. nativa/T. spiralis from Alaska and a T. spiralis/Trichinella T6 from California. The species identifications were confirmed using a conventional PCR targeting the rRNA ITS1-ITS2 region, followed by DNA sequencing analysis. The estimated limit of detection (LOD) was approximately seven larvae per gram of meat. MAIN CONCLUSIONS Differentiation of Trichinella spp. is needed to improve efforts on identification of case, optimize food safety control and better understand the geographic distribution of Trichinella species. The Trichinella qPCR multiplex proved to be a robust, easy to perform assay and is presented as an improved technique for identification of all known encapsulated species occurring in North America continent

Review of Telemicrobiology

Microbiology laboratories are continually pursuing means to improve quality, rapidity, and efficiency of specimen analysis in the face of limited resources. One means by which to achieve these improvements is through the remote analysis of digital images. Telemicrobiology enables the remote interpretation of images of microbiology specimens. To date, the practice of clinical telemicrobiology has not been thoroughly reviewed.Context.— To identify the various methods that can be employed for telemicrobiology, including emerging technologies that may provide value to the clinical laboratory.Objective.— Peer-reviewed literature, conference proceedings, meeting presentations, and expert opinions pertaining to telemicrobiology have been evaluated.Data Sources.— A number of modalities have been employed for telemicroscopy, including static capture techniques, whole slide imaging, video telemicroscopy, mobile devices, and hybrid systems. Telemicrobiology has been successfully implemented for several applications, including routine primary diagnosis, expert teleconsultation, and proficiency testing. Emerging areas of telemicrobiology include digital plate reading of bacterial cultures, mobile health applications, and computer-augmented analysis of digital images. To date, static image capture techniques have been the most widely used modality for telemicrobiology, despite newer technologies being available that may produce better quality interpretations. Telemicrobiology adds value, quality, and efficiency to the clinical microbiology laboratory, and increased adoption of telemicrobiology is anticipated.Conclusions.— </jats:sec

Micromorphology and microchemistry of selected Cryosols from maritime Antarctica

Little information is available on the microstructure of Cryosols from maritime Antarctica, and the present study characterizes the main soil types commonly found in ice-free areas of Admiralty Bay, King George Island. Four pedons were selected for micromorphological and microprobe analysis. The type of microstructure observed in the soils is strongly influenced by the lithological composition and arrangement, with a high proportion of primary minerals in all particle fractions. The oxidation of sulphides is the most important pedogenetic process in acid sulphate soils from maritime Antarctica and results in intense chemical weathering of minerals and formation of Na-jarosite, amorphous Fe-oxides and kaolinite. Jarosite forms illuvial coating within cryodesiccation fractures and is associated with large amounts of amorphous Fe minerals that possess a high P adsorption capacity. In ornithogenic soils, the phosphatization process enhances soil acidity and chemical alteration of the substrate and is the main soil-forming process in ornithogenic soils. P-rich solutions penetrate cryodesiccation fractures and cleavage planes in large clasts and preferentially react with volcanic glass. Soil reaction with P-rich leachates leads to the progressive displacement of Si from rock minerals, coupled with reacting of P with Al, Fe, K and Mg to form various amorphous and crystalline P forms. Cryoclastic weathering and cryoturbation result in high levels of fine P-rich aggregates down the profile. Chemical weathering is more pronounced in maritime Antarctica than previously thought, especially for acid sulphate and ornithogenic soils. The utilization of micromorphological and microchemical techniques proved to be extremely useful for a better understanding of pedogenesis in these poorly known Antarctic soils