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Abstract The treatment of invasive aspergillosis caused by cryptic species remains a challenge due to the lack of randomised clinical trials and investigation of the efficacy and safety of different therapeutic strategies. We aime...
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Abstract The treatment of invasive aspergillosis caused by cryptic species remains a challenge due to the lack of randomised clinical trials and investigation of the efficacy and safety of different therapeutic strategies. We aimed to evaluate the in vitro activity of 23 conventional and new antifungal drugs against 54 clinical and environmental Aspergillus oryzae isolates by using the Clinical and Laboratory Standards Institute (CLSI) standard M38‐A3. The lowest geometric mean MIC values were found for luliconazole and lanoconazole (0.001?μg/ml), followed by anidulafungin (0.104?μg/ml), posaconazole (0.15?μg/ml), itraconazole (0.37?μg/ml), efinaconazole (0.5?μg/ml), voriconazole (0.51?μg/ml), tavaborole (0.72?μg/ml), and amphotericin B (0.79?μg/ml). In contrast, ketoconazole, terbinafine, econazole, tioconazole, ravuconazole, miconazole, nystatin, clotrimazole, griseofulvin, sertaconazole, natamycin, tolnaftate, and fluconazole had no or low activity. Further studies are required to determine how well this in vitro activity translates into in vivo efficacy.
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摘要 :
The treatment of invasive aspergillosis caused by cryptic species remains a challenge due to the lack of randomised clinical trials and investigation of the efficacy and safety of different therapeutic strategies. We aimed to eval...
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The treatment of invasive aspergillosis caused by cryptic species remains a challenge due to the lack of randomised clinical trials and investigation of the efficacy and safety of different therapeutic strategies. We aimed to evaluate the in vitro activity of 23 conventional and new antifungal drugs against 54 clinical and environmental Aspergillus oryzae isolates by using the Clinical and Laboratory Standards Institute (CLSI) standard M38-A3. The lowest geometric mean MIC values were found for luliconazole and lanoconazole (0.001 μg/ml), followed by anidulafungin (0.104pg/ ml), posaconazole (0.15μg/ml), itraconazole (0.37μg/ml), efinaconazole (0.5 μg/ml), voriconazole (0.51μg/ml), tavaborole (0.72μg/ml), and amphotericin B (0.79μg/ml). In contrast, ketoconazole, terbinafine, econazole, tioconazole, ravuconazole, miconazole, nystatin, clotrimazole, griseofulvin, sertaconazole, natamycin, tolnaftate, and fluconazole had no or low activity. Further studies are required to determine how well this in vitro activity translates into in vivo efficacy.
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Adaptation of populations takes place with the occurrence and subsequent fixation of mutations that confer some selective advantage to the individuals which acquire it. For this reason, the study of the process of fixation of adva...
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Adaptation of populations takes place with the occurrence and subsequent fixation of mutations that confer some selective advantage to the individuals which acquire it. For this reason, the study of the process of fixation of advantageous mutations has a long history in the population genetics literature. Particularly, the previous investigations aimed to find out the main evolutionary forces affecting the strength of natural selection in the populations. In the current work, we investigate the dynamics of fixation of beneficial mutations in a subdivided population. The subpopulations (demes) can exchange migrants among their neighbors, in a migration network which is assumed to have either a random graph or a scale-free topology. We have observed that the migration rate drastically affects the dynamics of mutation fixation, despite of the fact that the probability of fixation is invariant on the migration rate, accordingly to Maruyama’s conjecture. In addition, we have noticed a topological dependence of the adaptive evolution of the population when clonal interference becomes effective.
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摘要 :
Adaptation of populations takes place with the occurrence and subsequent fixation of mutations
that confer some selective advantage to the individuals which acquire it. For this reason, the study
of the process of fixation of adva...
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Adaptation of populations takes place with the occurrence and subsequent fixation of mutations
that confer some selective advantage to the individuals which acquire it. For this reason, the study
of the process of fixation of advantageous mutations has a long history in the population genetics literature.
Particularly, the previous investigations aimed to find out the main evolutionary forces affecting
the strength of natural selection in the populations. In the current work, we investigate the dynamics of
fixation of beneficial mutations in a subdivided population. The subpopulations (demes) can exchange migrants
among their neighbors, in a migration network which is assumed to have either a random graph or a
scale-free topology. We have observed that the migration rate drastically affects the dynamics of mutation
fixation, despite of the fact that the probability of fixation is invariant on the migration rate, accordingly
to Maruyama’s conjecture. In addition, we have noticed a topological dependence of the adaptive evolution
of the population when clonal interference becomes effective.
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Magnetic susceptibility describes the magnetizability of a material to an applied magnetic field and represents an important parameter in the field of MRI. With the recently introduced method of quantitative susceptibility mapping...
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Magnetic susceptibility describes the magnetizability of a material to an applied magnetic field and represents an important parameter in the field of MRI. With the recently introduced method of quantitative susceptibility mapping (QSM) and its conceptual extension to susceptibility tensor imaging (STI), the non-invasive assessment of this important physical quantity has become possible with MRI. Both methods solve the ill-posed inverse problem to determine the magnetic susceptibility from local magnetic fields. Whilst QSM allows the extraction of the spatial distribution of the bulk magnetic susceptibility from a single measurement, STI enables the quantification of magnetic susceptibility anisotropy, but requires multiple measurements with different orientations of the object relative to the main static magnetic field. In this review, we briefly recapitulate the fundamental theoretical foundation of QSM and STI, as well as computational strategies for the characterization of magnetic susceptibility with MRI phase data. In the second part, we provide an overview of current methodological and clinical applications of QSM with a focus on brain imaging. Copyright (C) 2016 John Wiley & Sons, Ltd.
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Purpose To develop a susceptibility‐based MRI technique for probing microstructure and fiber architecture of magnetically anisotropic tissues—such as central nervous system white matter, renal tubules, and myocardial fibers—in ...
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Purpose To develop a susceptibility‐based MRI technique for probing microstructure and fiber architecture of magnetically anisotropic tissues—such as central nervous system white matter, renal tubules, and myocardial fibers—in three dimensions using susceptibility tensor imaging (STI) tools. Theory and Methods STI can probe tissue microstructure, but is limited by reconstruction artifacts because of absent phase information outside the tissue and noise. STI accuracy may be improved by estimating a joint eigenvector from mutually anisotropic susceptibility and relaxation tensors. Gradient‐recalled echo image data were simulated using a numerical phantom and acquired from the ex vivo mouse brain, kidney, and heart. Susceptibility tensor data were reconstructed using STI, regularized STI, and the proposed algorithm of mutually anisotropic and joint eigenvector STI (MAJESTI). Fiber map and tractography results from each technique were compared with diffusion tensor data. Results MAJESTI reduced the estimated susceptibility tensor orientation error by 30% in the phantom, 36% in brain white matter, 40% in the inner medulla of the kidney, and 45% in myocardium. This improved the continuity and consistency of susceptibility‐based fiber tractography in each tissue. Conclusion MAJESTI estimation of the susceptibility tensors yields lower orientation errors for susceptibility‐based fiber mapping and tractography in the intact brain, kidney, and heart. Magn Reson Med 77:2331–2346, 2017. ? 2016 International Society for Magnetic Resonance in Medicine
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Magnetic-susceptibility-based MRI has made important contributions to the characterization of tissue microstructure, chemical composition, and organ function. This has motivated a number of studies to explore the link between micr...
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Magnetic-susceptibility-based MRI has made important contributions to the characterization of tissue microstructure, chemical composition, and organ function. This has motivated a number of studies to explore the link between microstructure and susceptibility in organs and tissues throughout the body, including the kidney, heart, and connective tissue. These organs and tissues have anisotropic magnetic susceptibility properties and cellular organizations that are distinct from the lipid organization of myelin in the brain. For instance, anisotropy is traced to the epithelial lipid orientation in the kidney, the myofilament proteins in the heart, and the collagen fibrils in the knee cartilage. The magnetic susceptibility properties of these and other tissues are quantified using specific MRI tools: susceptibility tensor imaging (STI), quantitative susceptibility mapping (QSM), and individual QSM measurements with respect to tubular and filament directions determined from diffusion tensor imaging. These techniques provide complementary and supplementary information to that produced by traditional MRI methods. In the kidney, STI can track tubules in all layers including the cortex, outer medulla, and inner medulla. In the heart, STI detected myofibers throughout the myocardium. QSM in the knee revealed three unique layers in articular cartilage by exploiting the anisotropic susceptibility features of collagen. While QSM and STI are promising tools to study tissue susceptibility, certain technical challenges must be overcome in order to realize routine clinical use. This paper reviews essential experimental findings of susceptibility anisotropy in the body, the underlying mechanisms, and the associated MRI methodologies. Copyright (C) 2016 John Wiley & Sons, Ltd.
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Thermally sensitized 304 stainless steels, irradiated up to 1.2 x 10(21) n/cm(2) (E > 1 MeV), were slow-strain-rate-tensile tested in 290 degrees C water containing 0.2 ppm dissolved oxygen (DO), followed by scanning and transmiss...
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Thermally sensitized 304 stainless steels, irradiated up to 1.2 x 10(21) n/cm(2) (E > 1 MeV), were slow-strain-rate-tensile tested in 290 degrees C water containing 0.2 ppm dissolved oxygen (DO), followed by scanning and transmission electron microscopic examinations, to study mechanism of irradiation-assisted-stress-corrosioti-crack (IASCC) initiation. Intergranular (IG) cracking behaviors changed at a border fluence (around 1 x 10(20) n/cm(2)), above which deformation twinning were predominant and deformation localization occurred earlier with increasing fluence. The crack initiation sites tended to link to the deformation bands, indicating that the crack initiation may be brought about by the deformation bands interacted with grain boundaries. Thus the border fluence is equivalent to the IASCC threshold fluence for the sensitized material, although the terminology of IASCC is originally given to the non-sensitized materials without microstructural definition. The IASCC threshold fluence was found to change with irradiation conditions. Changes in IASCC susceptibility and IASCC threshold fluence with fluence and DO were further discussed. (c) 2005 Elsevier B.V. All rights reserved.
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Magnetic materials are useful in myriad ways, playing a critical role in modern society. Magnetic measurements, however, serve a much larger purpose than solely characterizing magnetic materials. Information obtained from magnetic...
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Magnetic materials are useful in myriad ways, playing a critical role in modern society. Magnetic measurements, however, serve a much larger purpose than solely characterizing magnetic materials. Information obtained from magnetic measurements is essential across a wide swathe of materials, ranging from topological quantum materials to catalysts and battery materials. As with many advanced characterization and measurement techniques, practical aspects of magnetic measurements requires experience that is not readily gained from textbooks and user manuals. As one example, the nature of the measurement and the interpretation of data can be strongly sample-dependent, and appropriate experimental design is essential to obtain reliable results in an efficient manner. In this "Methods and Protocols" contribution, we seek to demystify magnetic measurements for nonexperts, discussing best practices for a range of different magnetic measurements with illustrative examples.
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Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance ove...
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Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
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