Benefit from high intrarenal levels of gentamicin in the treatment of E. coli pyelonephritis

Benefit from high intrarenal levels of gentamicin in the treatment of E. coli pyelonephritis. The importance of high intrarenal levels of gentamicin on the outcome of experimental pyelonephritis was studied in rats receiving either a short course (three days) of gentamicin (G) alone or combined with a longer course (14 days) of ampicillin (A), cephalothin (C), or trimethoprim (T), or two weeks of therapy with ampicillin, cephalothin, trimethoprim and gentamicin given alone. While ampicillin, cephalothin and trimethoprim were undetectable in the medulla within six hours of cessation of therapy, gentamicin was still detectable in levels six folds above the MIC up to six months after treatment had ceased. Six months after the end of treatment, the percentage of sterile left kidneys in animals treated with ampicillin (50%), cephalothin (15%), trimethoprim (20%) was lower than the percentage of animals receiving 14 days of gentamicin (100%), or the combinations AG:89%, CG:67% and TG:60%, P < 0.01. Following three days of gentamicin, 50% of the left kidneys were sterilized. When compared to ampicillin, cephalothin or trimethoprim alone, combined therapies significantly reduced the number of CFU in the kidneys P < 0.01. These combinations were almost as effective as two weeks of therapy with gentamicin. Short–term therapy (three days) with an aminoglycoside which concentrates in the renal parenchyma, combined with an antibiotic which will accumulate in other parts of the nephron, may result in “pharmacological synergy”. This new approach to therapy of pyelonephritis may be promising

ASSESSING IMPACTS OF ENVIRONMENTAL CHANGE ON ABORIGINAL PEOPLE: AN ECONOMIC EXAMINATION OF SUBSISTENCE RESOURCE USE AND VALUE

The report describes the research design, data collection and preliminary analysis of an economic assessment of non-timber resource use by Aboriginal People in Northwest Saskatchewan. The project is designed to develop methods of valuing resource use by Aboriginal People so that these values can be incorporated into forest resource management decisions and to evaluate the impact of forest management actions on the economic well-being of Aboriginal People living in the region. Data on non-timber resource use are collected and spatially explicit economic models are developed in order to construct estimates of behavioral change and value associated with changes in the environment and landscape (through forestry, access, or other landscape changes).Environmental Economics and Policy, Resource /Energy Economics and Policy,

Converging Intracranial Markers of Conscious Access

We compared conscious and nonconscious processing of briefly flashed words using a visual masking procedure while recording intracranial electroencephalogram (iEEG) in ten patients. Nonconscious processing of masked words was observed in multiple cortical areas, mostly within an early time window (<300 ms), accompanied by induced gamma-band activity, but without coherent long-distance neural activity, suggesting a quickly dissipating feedforward wave. In contrast, conscious processing of unmasked words was characterized by the convergence of four distinct neurophysiological markers: sustained voltage changes, particularly in prefrontal cortex, large increases in spectral power in the gamma band, increases in long-distance phase synchrony in the beta range, and increases in long-range Granger causality. We argue that all of those measures provide distinct windows into the same distributed state of conscious processing. These results have a direct impact on current theoretical discussions concerning the neural correlates of conscious access

Polygenic risk scores predict diabetes complications and their response to intensive blood pressure and glucose control

Aims/hypothesis: Type 2 diabetes increases the risk of cardiovascular and renal complications, but early risk prediction could lead to timely intervention and better outcomes. Genetic information can be used to enable early detection of risk. Methods: We developed a multi-polygenic risk score (multiPRS) that combines ten weighted PRSs (10 wPRS) composed of 598 SNPs associated with main risk factors and outcomes of type 2 diabetes, derived from summary statistics data of genome-wide association studies. The 10 wPRS, first principal component of ethnicity, sex, age at onset and diabetes duration were included into one logistic regression model to predict micro- and macrovascular outcomes in 4098 participants in the ADVANCE study and 17,604 individuals with type 2 diabetes in the UK Biobank study. Results: The model showed a similar predictive performance for cardiovascular and renal complications in different cohorts. It identified the top 30% of ADVANCE participants with a mean of 3.1-fold increased risk of major micro- and macrovascular events (p = 6.3 × 10−21 and p = 9.6 × 10−31, respectively) and a 4.4-fold (p = 6.8 × 10−33) higher risk of cardiovascular death. While in ADVANCE overall, combined intensive blood pressure and glucose control decreased cardiovascular death by 24%, the model identified a high-risk group in whom it decreased the mortality rate by 47%, and a low-risk group in whom it had no discernible effect. High-risk individuals had the greatest absolute risk reduction with a number needed to treat of 12 to prevent one cardiovascular death over 5 years. Conclusions/interpretation: This novel multiPRS model stratified individuals with type 2 diabetes according to risk of complications and helped to target earlier those who would receive greater benefit from intensive therapy. Graphical abstract: [Figure not available: see fulltext.

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

La prévision du risque politique liée aux investissements à l'étranger

[eng] The deterioration of the climate of investments abroad leads enterprises to estimate more precisely politic risks.. So, new systems for measuring these risks have been lately perfected, inclusive in France.. In this article, the authors review the classical methods before drawing up a panorama of these new systems.. Each one of the recent methodology is analyzed : dynamical segmentation, the method of scenarii, other technics of data analysis, are developped and illustrated through practical examples.. In conclusion, the authors present possible methodological inovations. [fre] La détérioration rapide du climat des investissements à l'étranger a conduit les entreprises à évaluer avec plus de précision les risques politiques.. Ce faisant, de nouvelles méthodologies d'évaluation ont récemment été mises au point, notamment en France.. Cet article dresse un panorama de ces nouvelles méthodes après avoir fait un examen critique des méthodes classiques.. Chacune des nouvelles approches : segmentation dynamique, approche par scénarii, utilisation des techniques d'analyses de données, y sont explosées et illustrées par des exemples concrets.. L'article se conclut par les perspectives d'innovation méthodologiques dans ce domaine complexe de l'évaluation des risques politiques.

ASSESSING IMPACTS OF ENVIRONMENTAL CHANGE ON ABORIGINAL PEOPLE: AN ECONOMIC EXAMINATION OF SUBSISTENCE RESOURCE USE AND VALUE

The report describes the research design, data collection and preliminary analysis of an economic assessment of non-timber resource use by Aboriginal People in Northwest Saskatchewan. The project is designed to develop methods of valuing resource use by Aboriginal People so that these values can be incorporated into forest resource management decisions and to evaluate the impact of forest management actions on the economic well-being of Aboriginal People living in the region. Data on non-timber resource use are collected and spatially explicit economic models are developed in order to construct estimates of behavioral change and value associated with changes in the environment and landscape (through forestry, access, or other landscape changes)