Aerosolized colistin as adjunctive treatment of ventilator-associated pneumonia due to multidrug-resistant Gram-negative bacteria: A prospective study

SummaryBackgroundVentilator-associated pneumonia (VAP) remains the leading cause of death in patients with intensive care unit (ICU) acquired infections associated with an attributable mortality around 30%. Increasing antimicrobial resistance in patients with VAP challenges intensivists to search for alternative therapeutic options. There is scarcity of data in the literature concerning the administration of aerosolized colistin in critically ill patients with VAP due to multidrug-resistant (MDR) Gram-negative pathogens.MethodsTo assess the safety and effectiveness of aerosolized colistin as an adjunctive to the intravenous antimicrobial therapy for the treatment of VAP due to MDR Gram-negative pathogens, we prospectively examined all patients, who received inhaled colistin.ResultsSixty critically ill patients with a mean APACHE II score 16.7, received aerosolized colistin for the treatment of VAP due to MDR pathogens [Acinetobacter baumannii (37/60 cases), Pseudomonas aeruginosa (12/60 cases) and Klebsiella pneumoniae strains (11/60 cases)]. Half of the isolated pathogens were susceptible only to colistin. Mean (±SD) daily dosage of aerosolized colistin was 2.2 (±0.7) million international units (IU). All patients received 2946 inhalations of colistin and the mean duration of administration was 16.4 days. Fifty-seven patients received concomitant intravenous treatment with colistin or other antimicrobial agents. Bacteriological and clinical response of VAP was observed in 50/60 (83.3%) patients. No adverse effects related to inhaled colistin were recorded. All cause hospital mortality was 25% while mortality attributable to VAP was 16.7%.ConclusionsAerosolized colistin may be considered as adjunctive to intravenous treatment in patients with VAP due to MDR Gram-negative bacteria susceptible to colistin in critically ill patients. Although colistin is safe and effective, the best route of administration remains unclear. In addition, controlled comparative studies are needed to establish its effectiveness and safety

Fairness Aware Counterfactuals for Subgroups

In this work, we present Fairness Aware Counterfactuals for Subgroups (FACTS), a framework for auditing subgroup fairness through counterfactual explanations. We start with revisiting (and generalizing) existing notions and introducing new, more refined notions of subgroup fairness. We aim to (a) formulate different aspects of the difficulty of individuals in certain subgroups to achieve recourse, i.e. receive the desired outcome, either at the micro level, considering members of the subgroup individually, or at the macro level, considering the subgroup as a whole, and (b) introduce notions of subgroup fairness that are robust, if not totally oblivious, to the cost of achieving recourse. We accompany these notions with an efficient, model-agnostic, highly parameterizable, and explainable framework for evaluating subgroup fairness. We demonstrate the advantages, the wide applicability, and the efficiency of our approach through a thorough experimental evaluation of different benchmark datasets

Comparative study of the AT1 receptor prodrug antagonist candesartan cilexetil with other sartans on the interactions with membrane bilayers

AbstractDrug–membrane interactions of the candesartan cilexetil (TCV-116) have been studied on molecular basis by applying various complementary biophysical techniques namely differential scanning calorimetry (DSC), Raman spectroscopy, small and wide angle X-ray scattering (SAXS and WAXS), solution 1H and 13C nuclear magnetic resonance (NMR) and solid state 13C and 31P (NMR) spectroscopies. In addition, 31P cross polarization (CP) NMR broadline fitting methodology in combination with ab initio computations has been applied. Finally molecular dynamics (MD) was applied to find the low energy conformation and position of candesartan cilexetil in the bilayers. Thus, the experimental results complemented with in silico MD results provided information on the localization, orientation, and dynamic properties of TCV-116 in the lipidic environment. The effects of this prodrug have been compared with other AT1 receptor antagonists hitherto studied. The prodrug TCV-116 as other sartans has been found to be accommodated in the polar/apolar interface of the bilayer. In particular, it anchors in the mesophase region of the lipid bilayers with the tetrazole group oriented toward the polar headgroup spanning from water interface toward the mesophase and upper segment of the hydrophobic region. In spite of their localization identity, their thermal and dynamic effects are distinct pointing out that each sartan has its own fingerprint of action in the membrane bilayer, which is determined by the parameters derived from the above mentioned biophysical techniques

Abandonment of Silvopastoral Practices Affects the Use of Habitats by the European Hare (<i>Lepus europaeus</i>)

Silvopasture, a traditional agroforestry practice, combines the presence of trees, shrubs, herbage, and livestock in time and space to provide multiple ecosystem services that contribute to human well-being. However, the abandonment of traditional agroforestry practices across Europe has led to substantial changes in vegetation characteristics, mainly due to woody plant expansion and, as a consequence, changes in wildlife that rely on open habitats. This study examines the effects of a 20-year abandonment of silvopastoral practices (i.e., livestock grazing and fuelwood harvesting) in a typical agroforestry Mediterranean landscape (kermes oak shrubland, natural grassland, and olive groves) on European hare (Lepus europaeus) habitat use. We estimated tree, shrub, and herb cover using a densitometer and hare habitat use using pellet counts within 2004-m2 rectangular plots in 2002, 2011, and 2021. Hare pellet density in olive groves was significantly lower in 2021 compared to 2002, while the opposite trend was found in grassland for the same period. Woody plant cover expanded from 2002 to 2021. We suggest that the woody plant encroachment that followed the abandonment of traditional silvopastoral practices in the area is the main driver behind the reported decline in hare use of the habitat, as it became less open and therefore less favorable for the species. Maintaining a mosaic of open and closed habitats at the landscape level, which was once provided by silvopastures, is vital for the conservation of this species

Efficient Online Scheduling of Electric Vehicle Charging Using a Service-Price Menu

Along with high penetration of Electric Vehicles (EVs), charging stations are required to service a large amount of charging requests while accounting for constraints on the station's peak electricity consumption. To this end, a charging station needs to make online charging scheduling decisions often under limited future information. An important challenge relates to the prioritization of EVs that have unknown valuations for different levels of charging services. In this paper, we take into consideration the inability of EV users to express these valuations explicitly. We consider a paradigm where a menu of possible charging schedules and corresponding prices is generated online. By letting the EV users pick their most preferable menu option, the proposed algorithm commits on each EV's charging completion time upon its arrival, achieves a near optimal total weighted charging completion time, and prevents the users from strategically misreporting their preferences, while offering a practical and implementable solution to the problem of EVs - charging station interaction

Fairness Aware Counterfactuals for Subgroups

POSTERInternational audienceIn this work, we present Fairness Aware Counterfactuals for Subgroups (FACTS), a framework for auditing subgroup fairness through counterfactual explanations. We start with revisiting (and generalizing) existing notions and introducing new, more refined notions of subgroup fairness. We aim to (a) formulate different aspects of the difficulty of individuals in certain subgroups to achieve recourse, i.e. receive the desired outcome, either at the micro level, considering members of the subgroup individually, or at the macro level, considering the subgroup as a whole, and (b) introduce notions of subgroup fairness that are robust, if not totally oblivious, to the cost of achieving recourse. We accompany these notions with an efficient, model-agnostic, highly parameterizable, and explainable framework for evaluating subgroup fairness. We demonstrate the advantages, the wide applicability, and the efficiency of our approach through a thorough experimental evaluation of different benchmark datasets

Documenting Greek Indigenous Germplasm of Cornelian Cherry (<i>Cornus mas</i> L.) for Sustainable Utilization: Molecular Authentication, Asexual Propagation, and Phytochemical Evaluation

Wild-growing Cornelian cherries (Cornus mas L., Cornaceae) are well-known native fruits in Greece since ancient times that are still consumed locally nowadays. Modern research has highlighted the value of Cornelian cherries as functional food with exceptional health benefits on account of the fruits’ biochemical profile. However, apart from local consumption directly from wild growing individuals, Greek native C. mas populations have not yet been investigated or sustainably utilized. A multifaceted evaluation was conducted herein including authorized collection-documentation, taxonomic identification, and molecular authentication (DNA barcoding), asexual propagation via cuttings and phytochemical evaluation (multiple antioxidant profiling) of neglected and underutilized Greek native C. mas germplasm sources. Successive botanical expeditions resulted in the collection of 18 samples of genotypes from distant C. mas populations across different natural habitats in Greece, most of which were DNA fingerprinted for the first time. Asexual propagation trials revealed high variability in rooting frequencies among Greek genotypes with low (50%) using external indole-3-butyric acid (IBA) hormone application on soft- or hard-wood cuttings. The comparative phytochemical evaluation of the studied Greek genotypes showed significant potential in terms of antioxidant activity (>80% radical scavenging activity in 13 genotypes), but with variable phenolic content (47.58–355.46 mg GAE/100 g), flavonoid content (0.15–0.86 mg CE/100 g), and vitamin C content (1–59 mg AAE/100 g). The collected material is currently maintained under ex situ conservation for long-term monitoring coupled with ongoing pilot cultivation trials. The pivotal data create for the first time a framework for the sustainable utilization of Greek native C. mas germplasm as a superfood with significant agronomic potential