The pharmacokinetics of once-daily dosing of ceftriaxone in critically ill patients

The aim of this study was to determine the pharmacokinetic profile of the normal recommended dose of ceftriaxone in critically ill patients and to establish whether the current daily dosing recommendation maintains plasma concentrations adequate for antibacterial efficacy. Ceftriaxone at a recommended dose of 2 g iv was administered od to 12 critically ill patients with severe sepsis and normal serum creatinine concentrations. Blood samples were taken at predetermined intervals over the first 24 h and on day 3 for measurement of ceftriaxone concentrations. There was wide variability in drug disposition, explained by the presence of variable renal function and identified by the measurement of creatinine clearance. In nine patients with normal renal function, there was a high level of creatinine clearance(mean +/- S.D., 41 +/- 12 mL/min) and volume of distribution (20 +/- 3.3 L), which resulted in an elimination half-life of 6.4 +/- 1.1 h. In comparison with normal subjects, ceftriaxone clearance was increased 100%, volume of distribution increased 90% and the elimination half-life was similar. Three patients had substantially suboptimal plasma ceftriaxone concentrations. We confirm previous findings that ceftriaxone clearance in critically ill patients correlates with renal clearance by glomerular filtration. The elimination half-life is prolonged (21.4 +/- 9.8 h) in critically ill patients with renal failure when compared with previously published data in non-critically ill patients with renal failure. We conclude that in critically ill patients with normal renal function, inadequate plasma concentrations may result following od bolus dosing of ceftriaxone. Drug accumulation may occur in critically ill patients with renal failure.

Sox18 is transiently expressed during angiogenesis in granulation tissue of skin wounds with an identical expression pattern to Flk-1 mRNA

Sox18 encodes a member of the Sry-related high mobility group box (SOX) family of developmental transcription factors. Examination of Sox18 expression during embryogenesis has shown that Sox18 is expressed transiently in endothelial cells of developing blood vessels, and mutations in Sox18 have been found to underlie the mouse vascular and hair follicle mutant ragged. In this study we have examined the expression of Sox18 in angiogenesis during wound healing. Full-thickness skin wounds were created in mice, and subsequent expression of vascular endothelial growth factor (VEGF), the VEGF receptor Flk-1, alpha1 (iv) collagen (Col4a1), and Sox18 were studied using in situ hybridization. As has been previously reported, VEGF was expressed predominantly in the keratinocytes at the wound margins. Sox18 expression was found Rye days after wounding during capillary sprouting in granulation tissue and persisted through the proliferative phase of healing, but was not detected in fully epithelialized wounds 21 days after wounding. Sox18 mRNA expression was detected in capillaries within the granulation tissue and showed an identical pattern of distribution to Flk-1 and Col4a1 mRNA expression in endothelial cells. Immunostaining with a polyclonal anti-Sox18 antibody showed SOX18 protein localized in capillary endothelial cells within the granulation tissue. capillaries in the subcutaneous tissue of unwounded skin showed no Sox18 expression. Sox18 may therefore represent a transcription factor involved in the induction of angiogenesis during wound healing and tissue repair, but not in the maintenance of endothelial cells in undamaged tissue.

Comparison of two population pharmacokinetic programs, NONMEM and P-PHARM, for tacrolimus

Objectives: To compare the population modelling programs NONMEM and P-PHARM during investigation of the pharmacokinetics of tacrolimus in paediatric liver-transplant recipients. Methods: Population pharmacokinetic analysis was performed using NONMEM and P-PHARM on retrospective data from 35 paediatric liver-transplant patients receiving tacrolimus therapy. The same data were presented to both programs. Maximum likelihood estimates were sought for apparent clearance (CL/F) and apparent volume of distribution (V/F). Covariates screened for influence on these parameters were weight, age, gender, post-operative day, days of tacrolimus therapy, transplant type, biliary reconstructive procedure, liver function tests, creatinine clearance, haematocrit, corticosteroid dose, and potential interacting drugs. Results: A satisfactory model was developed in both programs with a single categorical covariate - transplant type - providing stable parameter estimates and small, normally distributed (weighted) residuals. In NONMEM, the continuous covariates - age and liver function tests - improved modelling further. Mean parameter estimates were CL/F (whole liver) = 16.3 1/h, CL/F (cut-down liver) = 8.5 1/h and V/F = 565 1 in NONMEM, and CL/F = 8.3 1/h and V/F = 155 1 in P-PHARM. Individual Bayesian parameter estimates were CL/F (whole liver) = 17.9 +/- 8.8 1/h, CL/F (cutdown liver) = 11.6 +/- 18.8 1/h and V/F = 712 792 1 in NONMEM, and CL/F (whole liver) = 12.8 +/- 3.5 1/h, CL/F (cut-down liver) = 8.2 +/- 3.4 1/h and V/F = 221 1641 in P-PHARM. Marked interindividual kinetic variability (38-108%) and residual random error (approximately 3 ng/ml) were observed. P-PHARM was more user friendly and readily provided informative graphical presentation of results. NONMEM allowed a wider choice of errors for statistical modelling and coped better with complex covariate data sets. Conclusion: Results from parametric modelling programs can vary due to different algorithms employed to estimate parameters, alternative methods of covariate analysis and variations and limitations in the software itself.

Population pharmacokinetics of tacrolimus in adult kidney transplant recipients

Objectives: The aims of this study were to investigate the population pharmacokinetics of tacrolimus in adult kidney transplant recipients and to identify factors that explain variability. Methods: Population analysis was performed on retrospective data from 70 patients who received oral tacrolimus twice daily. Morning blood trough concentrations were measured by liquid chromatography-tandem mass spectrometry. Maximum likelihood estimates were sought for apparent clearance (CL/F) and apparent volume of distribution (V/F), with the use of NONMEM (GloboMax LLC, Hanover, Md). Factors screened for influence on these parameters were weight, age, gender, postoperative day, days of tacrolimus therapy, liver function tests, creatinine clearance, hematocrit fraction, corticosteroid dose, and potential interacting drugs. Results. CL/F was greater in patients with abnormally low hematocrit fraction (data from 21 patients only), and it decreased with increasing days of therapy and AST concentrations (P

Low-density koala (Phascolarctos cinereus) populations in the mulgalands of south-west Queensland. III. Broad-scale patterns of habitat use

To date there have been few quantitative studies of the distribution of, and relative habitat utilisation by, koalas in the mulgalands of Queensland. To examine these parameters we applied habitat-accessibility and relative habitat-utilisation indices to estimates of faecal pellet density sampled at 149 sites across the region. Modelling the presence of pellets using logistic regression showed that the potential range of accessible habitats and relative habitat use varied greatly across the region, with rainfall being probably the most important determinant of distribution. Within that distribution, landform and rainfall were both important factors affecting habitat preference. Modelling revealed vastly different probabilities of finding a pellet under trees depending on the tree species, canopy size, and location within the region.

Increase of the delivered energy probability in DES using a fuzzy probabilistic modeling

The paper proposes a methodology to increase the probability of delivering power to any load point by identifying new investments in distribution energy systems. The proposed methodology is based on statistical failure and repair data of distribution components and it uses a fuzzy-probabilistic modeling for the components outage parameters. The fuzzy membership functions of the outage parameters of each component are based on statistical records. A mixed integer nonlinear programming optimization model is developed in order to identify the adequate investments in distribution energy system components which allow increasing the probability of delivering power to any customer in the distribution system at the minimum possible cost for the system operator. To illustrate the application of the proposed methodology, the paper includes a case study that considers a 180 bus distribution network.

Distribution network short term scheduling in Smart Grid context

The large increase of Distributed Generation (DG) in Power Systems (PS) and specially in distribution networks makes the management of distribution generation resources an increasingly important issue. Beyond DG, other resources such as storage systems and demand response must be managed in order to obtain more efficient and “green” operation of PS. More players, such as aggregators or Virtual Power Players (VPP), that operate these kinds of resources will be appearing. This paper proposes a new methodology to solve the distribution network short term scheduling problem in the Smart Grid context. This methodology is based on a Genetic Algorithms (GA) approach for energy resource scheduling optimization and on PSCAD software to obtain realistic results for power system simulation. The paper includes a case study with 99 distributed generators, 208 loads and 27 storage units. The GA results for the determination of the economic dispatch considering the generation forecast, storage management and load curtailment in each period (one hour) are compared with the ones obtained with a Mixed Integer Non-Linear Programming (MINLP) approach.

Optimization techniques for power distribution planning with uncertainties: a comparative study

Important research effort has been devoted to the topic of optimal planning of distribution systems. The non linear nature of the system, the need to consider a large number of scenarios and the increasing necessity to deal with uncertainties make optimal planning in distribution systems a difficult task. Heuristic techniques approaches have been proposed to deal with these issues, overcoming some of the inherent difficulties of classic methodologies. This paper considers several methodologies used to address planning problems of electrical power distribution networks, namely mixedinteger linear programming (MILP), ant colony algorithms (AC), genetic algorithms (GA), tabu search (TS), branch exchange (BE), simulated annealing (SA) and the Bender´s decomposition deterministic non-linear optimization technique (BD). Adequacy of theses techniques to deal with uncertainties is discussed. The behaviour of each optimization technique is compared from the point of view of the obtained solution and of the methodology performance. The paper presents results of the application of these optimization techniques to a real case of a 10-kV electrical distribution system with 201 nodes that feeds an urban area.

Invasion success and development of benthic assemblages: effect of timing, duration of submersion and substrate type

Copyright © 2013 Elsevier Ltd. All rights reserved.

New records of mosquito species (Diptera: Culicidae) from Neuquén and La Rioja provinces, Argentina

The presence of Aedes aegypti is reported beyond its current limit of distribution in Argentina, in the city of Neuquén, Neuquén Province. Ovitraps were placed to collect Ae. aegypti eggs between December 2009 and April 2010. The geographical distribution of Culex eduardoi, Psorophora ciliata and Ps. cingulata is extended with new records from two provinces.

Seroepidemiology of hepatitis a and b in two urban communities of Rio de Janeiro, Brazil

Hepatitis B markers were determined in 397 individuals from Niterói and 680 from Nova Iguaçu and prevalences of 9.1% (1.0% of HBsAg and 8.1% of anti HBs) and 11.1% (1.8% of HBsAg and 9.3% of antiHBs) were found, respectively. The comparative prevalence of both markers in relation to age showed a higher prevalence of HBsAg in the group 21-50 years old. Considering the antiHBs antibody, it was demostrated a gradual increase with age, reaching 14.9% in Niterói and 29.1% in Nova Iguaçu in individuals over 51 years old. For hepatitis A, in 259 samples from Niterói, equally distributed by age groups, an overall prevalence of 74.5% of anti-HAV antibodies was found. This prevalence increases gradually reaching 90.0% at age over thirty. In 254 samples from Nova Iguaçu analysed, a prevalence of 90.5% of antibodies was encountered when the same criteria of distribution of samples were used. This level of prevalence reached 90.0% already in the age over ten years old. The tests were performed by enzyme immunoassay with reagents prepared in our laboratory.

MASS CONSERVATION ENHANCEMENT OF FREE BOUNDARY FLOWS IN COMPOSITES MANUFACTURING

Undesirable void formation during the injection phase of the liquid composite molding process can be understood as a consequence of the non-uniformity of the flow front progression, caused by the dual porosity of the fiber perform. Therefore the best examination of the void formation physics can be provided by a mesolevel analysis, where the characteristic dimension is given by the fiber tow diameter. In mesolevel analysis, liquid impregnation along two different scales; inside fiber tows and within the spaces between them; must be considered and the coupling between these flow regimes must be addressed. In such case, it is extremely important to account correctly for the surface tension effects, which can be modeled as capillary pressure applied at the flow front. When continues Galerkin method is used, exploiting elements with velocity components and pressure as nodal variables, strong numerical implementation of such boundary conditions leads to ill-posing of the problem, in terms of the weak classical as well as stabilized formulation. As a consequence, there is an error in mass conservation accumulated especially along the free flow front. This article presents a numerical procedure, which was formulated and implemented in the existing Free Boundary Program in order to significantly reduce this error.

Mass Conservation Enhancement of Free Boundary Mesolevel Flows during LCM Processes of Composites Manufacturing

Undesirable void formation during the injection phase of the liquid composite moulding process can be understood as a consequence of the non-uniformity of the flow front progression, caused by the dual porosity of the fibre perform. Therefore the best examination of the void formation physics can be provided by a mesolevel analysis, where the characteristic dimension is given by the fibre tow diameter. In mesolevel analysis, liquid impregnation along two different scales; inside fibre tows and within the open spaces between them; must be considered and the coupling between these flow regimes must be addressed. In such case, it is extremely important to account correctly for the surface tension effects, which can be modelled as capillary pressure applied at the flow front. Numerical implementation of such boundary conditions leads to ill-posing of the problem, in terms of the weak classical as well as stabilized formulation. As a consequence, there is an error in mass conservation accumulated especially along the free flow front. This contribution presents a numerical procedure, which was formulated and implemented in the existing Free Boundary Program in order to significantly reduce this error.

Immunodiagnosis of hydatid disease: evaluation of antigens from hydatid cyst fluid and the vesicularfluid of Taenia crassiceps metacestode

The specificity and sensitivity of the enzyme immunoassay (EIA), presently used in South America areas where hydatidosis caused by Echinococcus granulosus is endemic, was compared to two alternative EIA. One of these uses an hydatid antigen of different prepraration and the other vesicular fluid of Taenia crassiceps cisticerci (VFCC). The effect of previous neutralization in the serum sample of antibodies anti-normal ovine or murine sera and anti-phosphorylcholine on the diagnostic efficiency of these EIA was studied. The frequency of distribution of the titers obtained with normal sera, hydatid sera positive to DD5 test and hydatid sera negative to DD5 test in three EIA systems was analyzed. Results showed a significant decrease of sensitivity of the EIA using VFCC when compared to these EIA using hydatid antigens. This makes inconvenient the use of VFCC for the immunodiagnosis of hydatid disease. No significant differences between the two EIA using hydatid antigens were observed. SDS-PAGE analysis showed remarkable differences between the VFCC and the hydatid antigens composition and some differences among these latters probably due to manufacturing procedures.

Modified Discrete PSO to Increase the Delivered Energy Probability in Distribution energy Systems

This paper proposes a PSO based approach to increase the probability of delivering power to any load point by identifying new investments in distribution energy systems. The statistical failure and repair data of distribution components is the main basis of the proposed methodology that uses a fuzzyprobabilistic modeling for the components outage parameters. The fuzzy membership functions of the outage parameters of each component are based on statistical records. A Modified Discrete PSO optimization model is developed in order to identify the adequate investments in distribution energy system components which allow increasing the probability of delivering power to any customer in the distribution system at the minimum possible cost for the system operator. To illustrate the application of the proposed methodology, the paper includes a case study that considers a 180 bus distribution network.