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  • 1
    Online Resource
    Online Resource
    American Society for Microbiology ; 2019
    In:  Clinical Microbiology Reviews Vol. 32, No. 3 ( 2019-06-19)
    In: Clinical Microbiology Reviews, American Society for Microbiology, Vol. 32, No. 3 ( 2019-06-19)
    Abstract: Invasive fungal diseases carry high morbidity and mortality in patients undergoing chemotherapy for hematological malignancies or allogeneic hematopoietic stem cell transplantation. In order to prevent these life-threatening infections, antifungal chemoprophylaxis plays an important role in daily clinical practice. Broad-spectrum antifungal triazoles are widely used but exhibit disadvantages such as relevant drug-drug interactions. Therefore, amphotericin B products or echinocandins can be an alternative in selected patient populations. As these compounds are available as intravenous formulations only, there is growing interest in extended dosing regimens. Although not approved for these agents, this strategy is a rational option, as these compounds have properties suitable for this strategy, including dose-proportional pharmacokinetics, prolonged elimination half-life, and a large therapeutic window. As the use of extended dosing regimens in antifungal prophylaxis is expanding in clinical practice, we reviewed the pharmacokinetic and pharmacodynamic rationale for this strategy, animal model data, dose escalation studies, and clinical trials supporting this concept.
    Type of Medium: Online Resource
    ISSN: 0893-8512 , 1098-6618
    RVK:
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2019
    detail.hit.zdb_id: 1497041-7
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2016
    In:  Proceedings of the National Academy of Sciences Vol. 113, No. 43 ( 2016-10-25), p. 12065-12070
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 113, No. 43 ( 2016-10-25), p. 12065-12070
    Abstract: Earth sustains its magnetic field by a dynamo process driven by convection in the liquid outer core. Geodynamo simulations have been successful in reproducing many observed properties of the geomagnetic field. However, although theoretical considerations suggest that flow in the core is governed by a balance between Lorentz force, rotational force, and buoyancy (called MAC balance for Magnetic, Archimedean, Coriolis) with only minute roles for viscous and inertial forces, dynamo simulations must use viscosity values that are many orders of magnitude larger than in the core, due to computational constraints. In typical geodynamo models, viscous and inertial forces are not much smaller than the Coriolis force, and the Lorentz force plays a subdominant role; this has led to conclusions that these simulations are viscously controlled and do not represent the physics of the geodynamo. Here we show, by a direct analysis of the relevant forces, that a MAC balance can be achieved when the viscosity is reduced to values close to the current practical limit. Lorentz force, buoyancy, and the uncompensated (by pressure) part of the Coriolis force are of very similar strength, whereas viscous and inertial forces are smaller by a factor of at least 20 in the bulk of the fluid volume. Compared with nonmagnetic convection at otherwise identical parameters, the dynamo flow is of larger scale and is less invariant parallel to the rotation axis (less geostrophic), and convection transports twice as much heat, all of which is expected when the Lorentz force strongly influences the convection properties.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2016
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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