A Two-Threshold Model for Scaling Laws of Non-Interacting Snow Avalanches

The sizes of snow slab failure that trigger snow avalanches are power-law distributed. Such a power-law probability distribution function has also been proposed to characterize different landslide types. In order to understand this scaling for gravity driven systems, we introduce a two-threshold 2-d cellular automaton, in which failure occurs irreversibly. Taking snow slab avalanches as a model system, we find that the sizes of the largest avalanches just preceeding the lattice system breakdown are power law distributed. By tuning the maximum value of the ratio of the two failure thresholds our model reproduces the range of power law exponents observed for land-, rock- or snow avalanches. We suggest this control parameter represents the material cohesion anisotropy.Comment: accepted PR

Implications of the antiplatelet therapy gap left with discontinuation of prasugrel in Canada

Background The current Canadian Cardiovascular Society antiplatelet therapy guidelines recommend the use of ticagrelor or prasugrel over clopidogrel as first-line platelet P2Y12 receptor antagonists for treatment of moderate- to high-risk acute coronary syndromes. Recently, Effient (prasugrel [Eli Lilly Canada Inc, Toronto, Canada]) was discontinued by its distributor in Canada. Methods Five members of the Canadian Cardiovascular Society antiplatelet therapy 2018 guidelines committee undertook an independent, evidence-based review to outline patients for whom prasugrel should be the optimal P2Y12 agent and discuss alternative strategies to consider without prasugrel. Results Several clinical scenarios where prasugrel should be indicated are identified and discussed. Considerations to be undertaken for alternative therapies are summarized, including a review of national and international guidelines for de-escalation of P2Y12 receptor antagonists. Conclusions The discontinuation of prasugrel poses a challenge for clinicians. Clinicians must consider key factors in determining the best alternate therapy.Introduction Dans ses lignes directrices actuelles sur la thérapie antiplaquettaire, la Société canadienne de cardiologie recommande l’utilisation du ticagrélor ou du prasugrel plutôt que l’utilisation du clopidogrel comme antagonistes des récepteurs plaquettaires P2Y12 de première intention dans le traitement des patients qui présentent un risque modéré à élevé de syndromes coronariens aigus. Depuis peu, le distributeur a cessé la distribution d’Effient (prasugrel) au Canada. Méthodes Cinq membres du comité des lignes directrices 2018 sur la thérapie antiplaquettaire de la Société canadienne de cardiologie ont entrepris une revue indépendante fondée sur les données probantes pour dresser le profil des patients pour lesquels le prasugrel devrait être la meilleure option parmi les antagonistes des récepteurs P2Y12 et se pencher sur les traitements alternatifs en l'absence de prasugrel. Résultats Plusieurs scénarios cliniques où le prasugrel devrait être indiqué sont recensés et abordés. Les réflexions sur les solutions de rechange au traitement, notamment une revue des lignes directrices nationales et internationales en matière de désescalade des antagonistes des récepteurs P2Y12, sont présentées. Conclusions La cessation de la distribution du prasugrel pose problème aux cliniciens. Les cliniciens doivent tenir compte des facteurs clés pour déterminer le meilleur traitement de remplacement

Encompassing in stationary linear dynamic models

Digitised version produced by the EUI Library and made available online in 2020

Extragalactic Fields Optimized for Adaptive Optics

In this paper we present the coordinates of 67 55' x 55' patches of sky which have the rare combination of both high stellar surface density (>0.5 arcmin^{-2} with 13<R<16.5 mag) and low extinction (E(B-V)<0.1). These fields are ideal for adaptive-optics based follow-up of extragalactic targets. One region of sky, situated near Baade's Window, contains most of the patches we have identified. Our optimal field, centered at RA: 7h24m3s, Dec: -1deg27'15", has an additional advantage of being accessible from both hemispheres. We propose a figure of merit for quantifying real-world adaptive optics performance, and use this to analyze the performance of multi-conjugate adaptive optics in these fields. We also compare our results to those that would be obtained in existing deep fields. In some cases adaptive optics observations undertaken in the fields given in this paper would be orders of magnitude more efficient than equivalent observations undertaken in existing deep fields.Comment: 28 pages, 15 figures, 1 table; accepted for publication in PAS

Timing of antibiotic therapy in the ICU

Severe or life threatening infections are common among patients in the intensive care unit (ICU). Most infections in the ICU are bacterial or fungal in origin and require antimicrobial therapy for clinical resolution. Antibiotics are the cornerstone of therapy for infected critically ill patients. However, antibiotics are often not optimally administered resulting in less favorable patient outcomes including greater mortality. The timing of antibiotics in patients with life threatening infections including sepsis and septic shock is now recognized as one of the most important determinants of survival for this population. Individuals who have a delay in the administration of antibiotic therapy for serious infections can have a doubling or more in their mortality. Additionally, the timing of an appropriate antibiotic regimen, one that is active against the offending pathogens based on in vitro susceptibility, also influences survival. Thus not only is early empiric antibiotic administration important but the selection of those agents is crucial as well. The duration of antibiotic infusions, especially for β-lactams, can also influence antibiotic efficacy by increasing antimicrobial drug exposure for the offending pathogen. However, due to mounting antibiotic resistance, aggressive antimicrobial de-escalation based on microbiology results is necessary to counterbalance the pressures of early broad-spectrum antibiotic therapy. In this review, we examine time related variables impacting antibiotic optimization as it relates to the treatment of life threatening infections in the ICU. In addition to highlighting the importance of antibiotic timing in the ICU we hope to provide an approach to antimicrobials that also minimizes the unnecessary use of these agents. Such approaches will increasingly be linked to advances in molecular microbiology testing and artificial intelligence/machine learning. Such advances should help identify patients needing empiric antibiotic therapy at an earlier time point as well as the specific antibiotics required in order to avoid unnecessary administration of broad-spectrum antibiotics

Role of renal sympathetic nerve activity in volatile anesthesia's effect on renal excretory function

Regulation of fluid balance is pivotal during surgery and anesthesia and affects patient morbidity, mortality, and hospital length of stay. Retention of sodium and water is known to occur during surgery but the mechanisms are poorly defined. In this study, we explore how the volatile anesthetic sevoflurane influences renal function by affecting renal sympathetic nerve activity (RSNA). Our results demonstrate that sevoflurane induces renal sodium and water retention during pediatric anesthesia in association with elevated plasma concentration of renin but not arginine–vasopressin. The mechanisms are further explored in conscious and anesthetized ewes where we show that RSNA is increased by sevoflurane compared with when conscious. This is accompanied by renal sodium and water retention and decreased renal blood flow (RBF). Finally, we demonstrate that renal denervation normalizes renal excretory function and improves RBF during sevoflurane anesthesia in sheep. Taken together, this study describes a novel role of the renal sympathetic nerves in regulating renal function and blood flow during sevoflurane anesthesia

Plant Extracellular Vesicles and Nanovesicles: Focus on Secondary Metabolites, Proteins and Lipids with Perspectives on Their Potential and Sources

While human extracellular vesicles (EVs) have attracted a big deal of interest and have been extensively characterized over the last years, plant-derived EVs and nanovesicles have earned less attention and have remained poorly investigated. Although a series of investigations already revealed promising beneficial health effects and drug delivery properties, adequate (pre)clinical studies are rare. This fact might be caused by a lack of sources with appropriate qualities. Our study introduces plant cell suspension culture as a new and well controllable source for plant EVs. Plant cells, cultured in vitro, release EVs into the growth medium which could be harvested for pharmaceutical applications. In this investigation we characterized EVs and nanovesicles from distinct sources. Our findings regarding secondary metabolites indicate that these might not be packaged into EVs in an active manner but enriched in the membrane when lipophilic enough, since apparently lipophilic compounds were associated with nanovesicles while more hydrophilic structures were not consistently found. In addition, protein identification revealed a possible explanation for the mechanism of EV cell wall passage in plants, since cell wall hydrolases like 1,3-β-glucosidases, pectinesterases, polygalacturonases, β-galactosidases and β-xylosidase/α-L-arabinofuranosidase 2-like are present in plant EVs and nanovesicles which might facilitate cell wall transition. Further on, the identified proteins indicate that plant cells secrete EVs using similar mechanisms as animal cells to release exosomes and microvesicles