While the goal of universal drug susceptibility testing has been a key component of the WHO End TB Strategy, in practice, this remains inaccessible to many. Rapid molecular tests for tuberculosis ...(TB) and antituberculosis drug resistance could significantly improve access to testing. In this study, we evaluated the accuracy of the Akonni Biosystems XDR-TB (extensively drug-resistant TB) TruArray and lateral-flow-cell (XDR-LFC) assay (Akonni Biosystems, Inc., Frederick, MD, USA), a novel assay that detects mutations in seven genes associated with resistance to antituberculosis drugs:
, the
promoter, and the
promoter for isoniazid;
for rifampin;
for fluoroquinolones;
and the
promoter for kanamycin; and
for capreomycin and amikacin. We evaluated assay performance using direct sputum samples from 566 participants recruited in a prospective cohort in Moldova over 2 years. The sensitivity and specificity against the phenotypic reference were both 100% for isoniazid, 99.2% and 97.9% for rifampin, 84.8% and 99.1% for fluoroquinolones, 87.0% and 84.1% for kanamycin, 54.3% and 100% for capreomycin, and 79.2% and 100% for amikacin, respectively. Whole-genome sequencing data for a subsample of 272 isolates showed 95 to 99% concordance with the XDR-LFC-reported suspected mutations. The XDR-LFC assay demonstrated a high level of accuracy for multiple drugs and met the WHO's minimum target product profile criteria for isoniazid and rifampin, while the sensitivity for fluoroquinolones and amikacin fell below target thresholds, likely due to the absence of a
target in the assay. With optimization, the XDR-LFC shows promise as a novel near-patient technology to rapidly diagnose drug-resistant tuberculosis.
The brief description of the Letter of Intent proposing primarily to perform measurements of asymmetries of the DY pair production in collisions of non-polarized, longitudinally and transversally ...polarized protons and deuterons which provide an access to all leading twist collinear and TMD PDFs of quarks and anti-quarks in nucleons.
•Duration of DINA-plasma disruption scenarios is limited by the end of plasma CQ.•Using of constant CS and PF coil currents after CQ end may give incorrect results.•Inductive coupling between the CS ...and PF coils and VV.•EM loads on the tokamak components located outside VV.
One of the most crucial issues in the design of the ITER machine is the electromagnetic (EM) loads associated with eddy currents induced in the conducting structures during plasma disruptions. The ITER database contains tens of calculation scenarios for possible plasma disruption events. The duration of these scenarios is usually limited by the end of the plasma current quench when the toroidal plasma current decreases to zero. For further EM analysis, the currents in the poloidal field coils are conventionally assumed constant after the end of the current quench. Such approach is not good for estimation of electromagnetic loads acting on the tokamak components located outside vacuum vessel. A possible way to solve this problem is to employ pre-determined coil current variations over the entire period of observation including time interval after the current quench. This paper describes an approach to such electromagnetic calculations and comparative results for selected cases with/out an extended current-time specification.
The paper is devoted to the development of the models of magnetic shielding system for the ITER neutral beam injectors. As the reactor operation is quasistationary, the magnetic field reduction ...system of the injectors combines a passive magnetic shield and a set of active correction coils. Due to the strict restrictions on the field inside the injectors, precision computations are required during the design stage. A special attention has been paid to possible gaps between steel panels of the passive magnetic shields due to manufacturing and assembly inaccuracies. A set of models with different levels of detail has been built for the convergence study. It was shown that the mesh needs to have tens of millions finite elements to provide the required computational accuracy.
While there has been progress in detection of drug resistant tuberculosis globally, WHO estimates only about half of the patients with bacteriologically confirmed tuberculosis were tested for ...rifampicin resistance over the past two years. To close this drug resistance diagnostic gap, an expansion of testing for rifampicin and isoniazid resistance is critically needed. The Akonni Biosystem Integrated System combines DNA extraction and a Lab-on-a-Film assembly (LFA) to perform rapid probe and PCR-based detection of resistance associated mutations to first-line anti-tuberculosis drugs. Using raw sputum samples from 25 tuberculosis patients at risk for drug resistance, we conducted a proof-of-concept study of the Integrated System with an MDR-TB assay. Performance of the Integrated System was compared to liquid Mycobacteria Growth Indicator Tube (MGIT) culture reference phenotypes using 2012 WHO endorsed critical concentrations for rifampicin and isoniazid. The overall percent agreement for rifampicin and isoniazid was 91.7% and 100% respectively, with agreement for rifampicin increasing to 95.7% after low-level resistance mutations in rpoB were excluded. The Integrated System, combining DNA extraction and LFA amplification, is a promising new tool for detection of both rifampicin and isoniazid using liquefied raw sputum.
Numerical verification is presented for modelling the magnetic effect of concrete structures reinforced with steel rebar. The model is based on the filling factor concept and takes into account ...magnetic anisotropy associated with the rebar pattern. Test problems are solved that prove applicability of the model in case of nonlinear properties of the reinforcement steel. A nonuniform field distribution is studied for a reinforced structure with an internal field source. Accuracy of simulated field maps with high gradients near ends of modelled structures has been assessed. The model has been verified in comparative computations with the use of other models. As an example, the proposed approach has been applied to a simplified magnetic model of the ITER tokamak complex. Then fields perturbations associated with the tokamak building structures have been evaluated for the gas breakdown at plasma initiation.
Some aspects of electromagnetic (EM) simulation of the central divertor cassettes (CDC) in the ITER tokamak are described. The study is focused on EM loads anticipated on the plasma-facing units ...(PFU) of CDC. The paper is devoted to the EM simulations of the most dangerous scenarios associated with high mechanical stresses: fast downward vertical displacement events of Categories II and III with 36-ms linear current quench (FD VDE-II and FD VDE-III with 36-ms LCQ). The selected events have been analyzed using the original TORNADO code intended for simulation of transient EM processes in 3D solids using the finite element representation. Results of computations include evolutions of EM loads on PFUs in the form of integral EM forces and moments, their peak values and relevant time points.
Description of the irradiation facility and available parameters of the neutron and gamma exposures including the maximal integrated doses are presented in the paper. The research capabilities for ...radiation hardness tests of materials in high intensity beam of fast neutrons at the IBR-2 reactor of the Joint Institute for Nuclear Research in Dubna (Russia) are outlined.
Automated genotyping of drug-resistant Mycobacterium tuberculosis (MTB) directly from sputum is challenging for three primary reasons. First, the sample matrix, sputum, is highly viscous and ...heterogeneous, posing a challenge for sample processing. Second, acid-fast MTB bacilli are difficult to lyse. And third, there are hundreds of MTB mutations that confer drug resistance. An additional constraint is that MTB is most prevalent where test affordability is paramount. We address the challenge of sample homogenization and cell lysis using magnetic rotation of an external magnet, at high (5000) rpm, to induce the rotation of a disposable stir disc that causes chaotic mixing of glass beads (“MagVor”). Nucleic acid is purified using a pipet tip with an embedded matrix that isolates nucleic acid (“TruTip”). We address the challenge of cost and genotyping multiple mutations using 203 porous three-dimensional gel elements printed on a film substrate and enclosed in a microfluidic laminate assembly (“Lab-on-a-Film”). This Lab-on-a-Film assembly (LFA) serves as a platform for amplification, hybridization, washing, and fluorescent imaging, while maintaining a closed format to prevent amplicon contamination of the workspace. We integrated and automated MagVor homogenization, TruTip purification, and LFA amplification in a multisample, sputum-to-genotype system. Using this system, we report detection down to 43 cfu/mL of MTB bacilli from raw sputum.
•We present the way of modeling transient electro-magnetic loads on local conductive domains in the large magnetic system.•Simplification is achieved by decomposing of the problem, multi-scale ...integral-differential modeling and use of integral parameters.•The intrinsic scale of loads on a localized conductor with eddy is quantified through the load susceptibility tensor.•Solution is searched as response of a simple equivalent dynamic simulator, using control theory methods.•The concept is exemplified with multi-scenario assessment of EM eddy loads on ITER blanket modules.
The complexity of the electromagnetic (EM) response of the tokamak structures is one of the key and design-driving issues for the ITER. We consider the specifics of the assessment of ponderomotive forces, acting on local components of a large electro-physical device during electromagnetic transients. A strategy and approach is proposed for the operative EM loads modeling and analysis that enables design optimization at early phases of development. The paper describes a method of principal simplification of the mathematical model, based on the analysis and exploiting specific features and peculiarities of the relevant technical problem, determined by the design and operation of the device and system under consideration. The application of the method for predictive EM loads analysis and corresponding numerical calculations are exemplified for the localized ITER blanket components — shield modules. The example demonstrates the efficiency of EM load analysis in complex electromagnetic systems via a set of simplified models with different scope, contents and level of detail.
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