Concepts of flywheels for energy storage using autostable high-T(sub c) superconducting magnetic bearings

A flywheel for energy storage using autostable high-T(sub c) superconducting magnetic bearings has been built. The rotating disk has a total weight of 2.8 kg. The maximum speed is 9240 rpm. A process that allows accelerated, reliable and reproducible production of melt-textured superconducting material used for the bearings has been developed. In order to define optimum configurations for radial and axial bearings, interaction forces in three dimensions and vertical and horizontal stiffness have been measured between superconductors and permanent magnets in different geometries and various shapes. Static as well as dynamic measurements have been performed. Results are being reported and compared to theoretical models

Computer simulation of glioma growth and morphology

Despite major advances in the study of glioma, the quantitative links between intra-tumor molecular/cellular properties, clinically observable properties such as morphology, and critical tumor behaviors such as growth and invasiveness remain unclear, hampering more effective coupling of tumor physical characteristics with implications for prognosis and therapy. Although molecular biology, histopathology, and radiological imaging are employed in this endeavor, studies are severely challenged by the multitude of different physical scales involved in tumor growth, i.e., from molecular nanoscale to cell microscale and finally to tissue centimeter scale. Consequently, it is often difficult to determine the underlying dynamics across dimensions. New techniques are needed to tackle these issues. Here, we address this multi-scalar problem by employing a novel predictive three-dimensional mathematical and computational model based on first-principle equations (conservation laws of physics) that describe mathematically the diffusion of cell substrates and other processes determining tumor mass growth and invasion. The model uses conserved variables to represent known determinants of glioma behavior, e.g., cell density and oxygen concentration, as well as biological functional relationships and parameters linking phenomena at different scales whose specific forms and values are hypothesized and calculated based on in vitro and in vivo experiments and from histopathology of tissue specimens from human gliomas. This model enables correlation of glioma morphology to tumor growth by quantifying interdependence of tumor mass on the microenvironment (e.g., hypoxia, tissue disruption) and on the cellular phenotypes (e.g., mitosis and apoptosis rates, cell adhesion strength). Once functional relationships between variables and associated parameter values have been informed, e.g., from histopathology or intra-operative analysis, this model can be used for disease diagnosis/prognosis, hypothesis testing, and to guide surgery and therapy. In particular, this tool identifies and quantifies the effects of vascularization and other cell-scale glioma morphological characteristics as predictors of tumor-scale growth and invasion

Flea Diversity as an Element for Persistence of Plague Bacteria in an East African Plague Focus

Plague is a flea-borne rodent-associated zoonotic disease that is caused by Yersinia pestis and characterized by long quiescent periods punctuated by rapidly spreading epidemics and epizootics. How plague bacteria persist during inter-epizootic periods is poorly understood, yet is important for predicting when and where epizootics are likely to occur and for designing interventions aimed at local elimination of the pathogen. Existing hypotheses of how Y. pestis is maintained within plague foci typically center on host abundance or diversity, but little attention has been paid to the importance of flea diversity in enzootic maintenance. Our study compares host and flea abundance and diversity along an elevation gradient that spans from low elevation sites outside of a plague focus in the West Nile region of Uganda (∼725–1160 m) to higher elevation sites within the focus (∼1380–1630 m). Based on a year of sampling, we showed that host abundance and diversity, as well as total flea abundance on hosts was similar between sites inside compared with outside the plague focus. By contrast, flea diversity was significantly higher inside the focus than outside. Our study highlights the importance of considering flea diversity in models of Y. pestis persistence

Implémentation d’un protocole d’optimisation posologique de la vancomycine en néonatologie : quels impacts sur l’exposition à la vancomycine et l’évolution clinico-biologique ?

Thèse d'exercice commune de médecine pharmacie respectivement soutenue en médecine par Diane Boegler (spécialité : pédiatrie) et en pharmacie par Laura Gomez (spécialité : biologie médicale).Vancomycin, the commonly used antibiotic therapy for neonatal sepsis exhibits frequent insufficient steady state concentrations (Css). A vancomycin dose optimization protocol based on a previously published pharmacokinetic model has been implemented in the neonatal intensive care unit of the Grenoble Alpes University Hospital. Our aims were to compare the vancomycin exposure and biological and clinical parameters before and after implementation of this protocol. We performed a monocenter retrospective study. The primary endpoint was the proportion of initial vancomycin Css in the therapeutic range (15-25 mg/L). Clinical outcomes and biological parameters were also studied. Sixty and 59 vancomycin cures in 45 and 49 patients were analyzed in groups before and after intervention, respectively. Initial vancomycin Css were more frequently in the therapeutic range in the group after intervention (74.6% versus: 28.3% p<0.001), with 1.6-fold higher Css than in the group before (12.9 [11.3-17.0] mg/L, versus 20.3 [17.0-22.2] mg/L; p<0.001). Considering all Css during longitudinal therapeutic drug monitoring, frequency of therapeutic Css was increased in the group after intervention (vs after 74.8% (n= 103) vs before: 31% (n=116); p<0.001). The dose optimization protocol was also associated with a reduced time to blood culture negativation (p<0.001) and fewer antibiotic switches (p=0.025), without increasing the frequency of nephrotoxicity. Clinical outcomes seem also improved with less periventricular leukomalacia (p=0.021) and trends towards less respiratory instabilities (p=0.15), shorter duration of vasoactive drugs used (p=0.18) in neonates benefiting from personalized doses of vancomycin. In conclusions this vancomycin dose optimization protocol improved vancomycin exposure in neonates with good safety, and improved biological and clinical outcomes.La vancomycine, antibiotique couramment utilisé dans le traitement des septicémies néonatales, présente une pharmacocinétique très variable avec des concentrations très fréquemment insuffisantes. Devant ce constat, un protocole d'optimisation des doses de vancomycine, basé sur un modèle pharmacocinétique précédemment publié, a été mis en place dans le service de médecine néonatale du CHU Grenoble Alpes en septembre 2019. L'objectif de ce travail rétrospectif était d'évaluer l'impact de ce protocole sur l'exposition à la vancomycine ainsi que sur l’évolution de paramètres biologiques et cliniques, en comparant deux groupes, avant et après la mise en place de ce protocole, entre août 2018 et octobre 2020. Soixante et 59 cures de vancomycine chez 45 et 49 patients ont été respectivement analysées dans les groupes avant et après. Le critère de jugement principal était la proportion de concentration à l’équilibre (Css) initiale dans l’intervalle 15 à 25mg/L. La proportion de Css initiale de vancomycine dans l’intervalle thérapeutique était plus élevée dans le groupe après (avant : 28,3% vs après : 74,6% ; p<0,001). L’exposition globale en vancomycine était également améliorée dans le groupe après, avec davantage de Css thérapeutiques mesurées au cours du suivi thérapeutique pharmacologique longitudinal. Cette amélioration de l’exposition en vancomycine était associée à un délai de négativation des hémocultures plus court (p<0,001), moins de changements d'antibiotiques (p=0,025) et à une tendance à moins de rechutes (p=0,13), sans modification de la fréquence de survenue de néphrotoxicité (p=0,54). L’évolution clinique immédiate semblait meilleure avec des tendances à moins de majorations du support ventilatoire (p=0,15) et une durée d’utilisation des drogues vasoactives plus courte (p=0,18) dans le groupe après. L’évolution clinique à moyen terme semblait également meilleure avec moins de leucomalacie périventriculaire (p=0,021) et une tendance à moins de dysplasie broncho-pulmonaire sévère (p=0,066) dans le groupe après. En conclusion, ce protocole d'optimisation posologique de la vancomycine a permis d'améliorer considérablement l'exposition à la vancomycine chez les nouveau-nés sans majoration de la toxicité rénale, permettant une meilleure évolution clinico-biologique

Implémentation d’un protocole d’optimisation posologique de la vancomycine en néonatologie : quels impacts sur l’exposition à la vancomycine et l’évolution clinico-biologique ?

Thèse d'exercice commune de médecine pharmacie respectivement soutenue en médecine par Diane Boegler (spécialité : pédiatrie) et en pharmacie par Laura Gomez (spécialité : biologie médicale).Vancomycin, the commonly used antibiotic therapy for neonatal sepsis exhibits frequent insufficient steady state concentrations (Css). A vancomycin dose optimization protocol based on a previously published pharmacokinetic model has been implemented in the neonatal intensive care unit of the Grenoble Alpes University Hospital. Our aims were to compare the vancomycin exposure and biological and clinical parameters before and after implementation of this protocol. We performed a monocenter retrospective study. The primary endpoint was the proportion of initial vancomycin Css in the therapeutic range (15-25 mg/L). Clinical outcomes and biological parameters were also studied. Sixty and 59 vancomycin cures in 45 and 49 patients were analyzed in groups before and after intervention, respectively. Initial vancomycin Css were more frequently in the therapeutic range in the group after intervention (74.6% versus: 28.3% p<0.001), with 1.6-fold higher Css than in the group before (12.9 [11.3-17.0] mg/L, versus 20.3 [17.0-22.2] mg/L; p<0.001). Considering all Css during longitudinal therapeutic drug monitoring, frequency of therapeutic Css was increased in the group after intervention (vs after 74.8% (n= 103) vs before: 31% (n=116); p<0.001). The dose optimization protocol was also associated with a reduced time to blood culture negativation (p<0.001) and fewer antibiotic switches (p=0.025), without increasing the frequency of nephrotoxicity. Clinical outcomes seem also improved with less periventricular leukomalacia (p=0.021) and trends towards less respiratory instabilities (p=0.15), shorter duration of vasoactive drugs used (p=0.18) in neonates benefiting from personalized doses of vancomycin. In conclusions this vancomycin dose optimization protocol improved vancomycin exposure in neonates with good safety, and improved biological and clinical outcomes.La vancomycine, antibiotique couramment utilisé dans le traitement des septicémies néonatales, présente une pharmacocinétique très variable avec des concentrations très fréquemment insuffisantes. Devant ce constat, un protocole d'optimisation des doses de vancomycine, basé sur un modèle pharmacocinétique précédemment publié, a été mis en place dans le service de médecine néonatale du CHU Grenoble Alpes en septembre 2019. L'objectif de ce travail rétrospectif était d'évaluer l'impact de ce protocole sur l'exposition à la vancomycine ainsi que sur l’évolution de paramètres biologiques et cliniques, en comparant deux groupes, avant et après la mise en place de ce protocole, entre août 2018 et octobre 2020. Soixante et 59 cures de vancomycine chez 45 et 49 patients ont été respectivement analysées dans les groupes avant et après. Le critère de jugement principal était la proportion de concentration à l’équilibre (Css) initiale dans l’intervalle 15 à 25mg/L. La proportion de Css initiale de vancomycine dans l’intervalle thérapeutique était plus élevée dans le groupe après (avant : 28,3% vs après : 74,6% ; p<0,001). L’exposition globale en vancomycine était également améliorée dans le groupe après, avec davantage de Css thérapeutiques mesurées au cours du suivi thérapeutique pharmacologique longitudinal. Cette amélioration de l’exposition en vancomycine était associée à un délai de négativation des hémocultures plus court (p<0,001), moins de changements d'antibiotiques (p=0,025) et à une tendance à moins de rechutes (p=0,13), sans modification de la fréquence de survenue de néphrotoxicité (p=0,54). L’évolution clinique immédiate semblait meilleure avec des tendances à moins de majorations du support ventilatoire (p=0,15) et une durée d’utilisation des drogues vasoactives plus courte (p=0,18) dans le groupe après. L’évolution clinique à moyen terme semblait également meilleure avec moins de leucomalacie périventriculaire (p=0,021) et une tendance à moins de dysplasie broncho-pulmonaire sévère (p=0,066) dans le groupe après. En conclusion, ce protocole d'optimisation posologique de la vancomycine a permis d'améliorer considérablement l'exposition à la vancomycine chez les nouveau-nés sans majoration de la toxicité rénale, permettant une meilleure évolution clinico-biologique

Pathogenicity and Rapid Growth Kinetics of Feline Immunodeficiency Virus Are Linked to 3\u27 Elements

Chimeric viruses constructed between a highly pathogenic Feline Immunodeficiency Virus isolate (FIV-C36) and a less pathogenic but neurotropic strain (FIV-PPR) have been used to map viral genetic determinants of in vivo pathogenicity. Chimeric virus FIV-PCenv, which contains FIV-C36 genome from the 39 region of pol to upstream of the 3\u27LTR on an FIV-PPR backbone, was previously shown to be replication-competent in vivo, inducing altered CD4+ T-cell and neutrophil profiles intermediate between parental strains following a delay in viral replication during initial infection. Examination of FIV-PCenv proviral sequences recovered at week 11 post-infection revealed two changes compared to initial viral inoculum; the most significant being arginine to histidine in the integrase region of Pol at residue 813 (R813H). Pooled plasma from the initial in vivo study was used to inoculate a second cohort of cats to determine whether similar virulence and kinetics could be established following primary infection. Viral replication kinetics and immunocyte profiles were monitored in blood, bone marrow, and saliva over a one-year period. Passaged FIV-PCenv again displayed intermediate phenotype between parental strains, but unlike primary experiments, the onset of acute viremia was not delayed. CD4/8 alterations were noted in all groups of animals, though significant changes from controls were delayed in FIV-PPR infected animals compared to FIV-C36 and FIV-PCenv. In vivo passage of FIV-PCenv increased replication-competence relative to the initial molecularly-cloned chimera in association with one adaptive nucleotide change in the 59 end of the genome relative to primary tissue culture inoculum, while mutations in the 3\u27 end of the genome were not detected. The results are consistent with the interpretation that 3\u27 elements contribute to heightened virulence of FIV-C36, and that integrase residue 813 plays an important role in facilitating successful in vivo replication

Mist Netting Bias, Species Accumulation Curves, and the Rediscovery of Two Bats on Montserrat (Lesser Antilles)

Mist nets are commonly used to survey bat populations and to estimate bat biodiversity, but several studies have found that mist net capture data and methods are biased due to a number of factors, including size and placement of nets, and the frequency at which investigators check their nets. Despite the wealth of literature and anecdotal reports, few investigators have quantified the interactions of bats with mist nets directly. We employed night vision camcorders to monitor bat behavior when bats encountered a mist net and then utilized these data to reevaluate years of survey data collected on Montserrat, Lesser Antilles. We recorded 2,523 bat passes during 43.3 hours of videotaping in July 2005 and June 2006. Observations conducted on successive nights provide evidence of avoidance-learning behavior in bats. When a mist net was present, 5.4% of bats in the airspace came into contact with the net giving an overall capture rate of 3.2% (range 0–10.3%). Mist nets are not accurately sampling bats that utilize flyways on Montserrat and such fieldwork thereby generates potentially misleading data. Biodiversity assessments and conservation guidelines based on short-term mist net surveys alone are not sufficient or reliable in regards to bats. A pragmatic solution to reduce mist net bias is to repeatedly sample a target region, utilize a variety of netting sites, use variable net sets, and carefully analyze species accumulation curves