Population pharmacokinetics of ciprofloxacin in patients with liver impairments analyzed by NPEM2 algorithm--a retrospective study

In order to develop a population pharmacokinetic model for ciprofloxacin after single oral dosing in patients with liver impairments, a retrospective population analysis of already published data was undertaken. The purpose of the study was to compare the population model parameter estimates for ciprofloxacin obtained with the non-parametric expectation maximization (NPEM2) algorithm based on a full data set (NPEM2-FULL) with those based on a set of 3 randomly chosen time/concentrations data (NPEM2-3RPs). Parameter values generated by the standard two-stage (STS) approach using traditional data-rich situation were used as a "gold standard" for comparative purposes. There was no significant difference between parameter means at p < 0.05 for Gauss-Newton and maximum a posteriori Bayesian (MAPB) estimators. The values of k(s) (min/ml/h) as estimated by STS and NPEM2-FULL models, on the one hand, and by STS and NPEM2-3RPs population models on the other hand (0.001, 0.00095, and 0.001, respectively), were not significantly different (p = 0.1457, respectively p = 0.6276). The population models values of k(s) suggest that good approximation between ciprofloxacin renal clearance and creatinine clearance could be expected for most of the patients and support previous observations that creatinine clearance is a meaningful predictor for ciprofloxacin elimination from the body. The 3 population models estimated Vs/F (l/kg) without significant difference. The predictive performance of these population models was subsequently assessed using internal validation approach. The 3 population models demonstrated comparable accuracy and precision in Bayesian forecasting of drug plasma levels of validation group patients based on 1 random and 2 suboptimal prior drug concentrations. There was, however, a one-order of magnitude decrease in population models bias when 2 suboptimal data points were used as Bayesian priors.     

A Language for Content-Based Video Retrieval

We present an effective technique for automatic extraction, representation, and classification of digital video, and a visual language for formulation of queries to access the semantic information contained in digital video. We have devised an algorithm that extracts motion information from a video sequence. This algorithm provides a low-cost extension to the motion compensation component of the MPEG compression algorithm. In this paper, we present a visual language called VEVA for querying multimedia information in general, and video semantic information in particular. Unlike many other proposals that concentrate on browsing the data, VEVA offers a complete set of capabilities for specifying relationships between the image components and formulating queries that search for objects, their motions and their other associated characteristics. VEVA has been shown to be very expressive in this context mainly due to the fact that many types of multimedia information are inherently visual in nature.     

GeD spline estimation of multivariate Archimedean copulas

A new multivariate Archimedean copula estimation method is proposed in a non-parametric setting. The method uses the so-called Geometrically Designed splines (GeD splines) to represent the cdf of a random variable W_θ, obtained through the probability integral transform of an Archimedean copula with parameter θ. Sufficient conditions for the GeD spline estimator to possess the properties of the underlying theoretical cdf, K(θ,t), of W_θ, are given. The latter conditions allow for defining a three-step estimation procedure for solving the resulting non-linear regression problem with linear inequality constraints. In the proposed procedure, finding the number and location of the knots and the coefficients of the unconstrained GeD spline estimator and solving the constraint least-squares optimisation problem are separated. Thus, the resulting spline estimator is used to recover the generator and the related Archimedean copula by solving an ordinary differential equation. The proposed method is truly multivariate, it brings about numerical efficiency and as a result can be applied with large volumes of data and for dimensions d≥2, as illustrated by the numerical examples presented.     

Development of model aqueous ophthalmic solution of indomethacin

A new model aqueous solution of indomethacin was developed on the basis of Pluronic™ F68 (15%) and F127 (10%). They showed some practical advantages over the models prepared with polyols and polysorbate 80, which were used for comparison. It was found that both Pluronics acted very similarly and were more effective as solubilizers, created an appropriate viscosity, and formed reversible gels at higher temperatures, ensured the indomethacin chemical stability and prolonged in vitro drug diffusion, and showed high physiological tolerance on rabbit eyes. Moreover, indomethacin stability and solution viscosity in the presence of Pluronics did not change after heat sterilization (i.e., the samples can bear heat sterilization).     

Uplink packet scheduling in cellular networks with?relaying��comparative study

Deployment of intermediate relay nodes in cellular networks, e.g. UMTS/ HSPA, has been proposed for service enhancement, which is of particular importance for uplink users at the cell edge suffering from low power capacity and relatively poor channel conditions. In this paper, we propose and investigate a number of uplink packet scheduling schemes deploying the relay functionality in different ways. Using a combined packet and flow level analysis capturing the specifics of the scheduling schemes and the random behavior of the users (initiation and completion of flow transfers), the performance of the various schemes is evaluated and compared to a reference scenario where relaying is not used. The main performance measures considered in our study are realized data rates and mean flow transfer times. Interestingly, considering flow transfer times, it is found that the use of relay nodes is not only particularly beneficial for users at the cell edge but also has a strong, positive effect on the performance of users at other locations not transmitting via a relay node.     

Anti-inflammatory activity of Devil’s claw in vitro systems and their active constituents

Cell suspension and Agrobacterium rhizogenes-transformed hairy root cultures of Devil’s claw (Harpagophytum procumbens), an African plant with high medicinal value, were cultivated in shake-flasks. A purification scheme to isolate their main active constituents (the phenylethanoid glycosides verbascoside, leucosceptoside A, β-OH-verbascoside and martynoside; structurally identified by NMR and LC–MS) was then developed, and their concentrations in the cultures were determined by UV spectrometry following HPLC separation. Preparations, extracts and the isolated phenylethanoid glycosides from the H. procumbens in vitro systems were tested on isolated murine macrophages to study their effects on nitric oxide (NO) and cytokine (TNF-α, IL-6) release and the expression of COX-1 and COX-2. They were also added to human serum to investigate their effects on the classical pathway of complement activation. The results indicate that the extracts and preparations of the in vitro systems, and pure verbascoside (their main active constituent), had strong anti-inflammatory properties, comparable to or even higher than that of pure harpagoside (a major anti-inflammatory constituent of intact Devil’s claw tubers). Thus, they have potential as new anti-inflammatory agents.     

Fundamentals of power spectra of extracellular potentials produced by a skeletal muscle fibre of finite length. Part I: Effect of fibre anatomy

To provide a thorough understanding of the changes in the power spectrum of electromyographic (EMG) signals, the formation of the power spectrum (PS) of extracellular potentials (EPs) produced by a skeletal muscle fibre of finite length was analysed. It was shown that, as in the case of an infinite fibre, the PS could be represented as the product of power spectra of the input signal (the first temporal derivative of the intracellular action potential, IAP) and of the impulse response (IR) of the fibre of finite length as a system of EP generation. The interrelations between the two multipliers determine the sensitivity of the EP power spectrum to alterations in parameters. The anatomical parameters of the fibre (length, depth, position of the end-plate in respect of the fibre ends) affect the EP power spectrum through IR power spectrum. Variations of the EP characteristic frequencies along the fibre length as well as oscillations in the PS are intrinsic properties of the fibre of finite length.     

Oculo-facio-cardio-dental (OFCD) syndrome

OBJECTIVE: This study examined the effects on SPECT quantitation caused by erroneous size and position of the attenuation map and inaccurate pixel size used in the Chang algorithm. METHODS: Projection data of a three-dimensional head phantom were simulated with a uniform attenuation coefficient of 0.15/cm for the inside of the phantom. Images were reconstructed using the filtered backprojection algorithm without attenuation compensation and the Chang algorithm with different attenuation maps. Quantitative comparison then was performed between the reconstructed images and the phantom. RESULTS: The pixel values obtained for noisy data by using the first-order Chang algorithm with an accurate attenuation map were less than 10% different from the true values and the left-right asymmetry was under 5%. Small errors in the geometric parameters of the attenuation map, however, caused considerable quantitative inaccuracy in the reconstructed image. For example, a 0.64-cm error in the size of the map caused 10% deviation from the true value and a 0.64-cm shift of the position of the map towards the left produced 10% left-right pixel value asymmetry. CONCLUSION: The accuracy of the Chang algorithm critically depends on the geometric parameters. For a uniform attenuator with symmetric geometry, such as the human brain, a true left-right symmetry in the pixel value can be altered significantly by a small error in the geometric parameters, while symmetry can be maintained with no attenuation compensation.     

Study and design of a hybrid wind–diesel-compressed air energy storage system for remote areas

Remote areas around the world predominantly rely on diesel-powered generators for their electricity supply, a relatively expensive and inefficient technology that is responsible for the emission of 1.2 million tons of greenhouse gas (GHG) annually, only in Canada [1]. Wind–diesel hybrid systems (WDS) with various penetration rates have been experimented to reduce diesel consumption of the generators. After having experimented wind–diesel hybrid systems (WDS) that used various penetration rates, we turned our focus to that the re-engineering of existing diesel power plants can be achieved most efficiently, in terms of cost and diesel consumption, through the introduction of high penetration wind systems combined with compressed air energy storage (CAES). This article compares the available technical alternatives to supercharge the diesel that was used in this high penetration wind–diesel system with compressed air storage (WDCAS), in order to identify the one that optimizes its cost and performances. The technical characteristics and performances of the best candidate technology are subsequently assessed at different working regimes in order to evaluate the varying effects on the system. Finally, a specific WDCAS system with diesel engine downsizing is explored. This proposed design, that requires the repowering of existing facilities, leads to heightened diesel power output, increased engine lifetime and efficiency and to the reduction of fuel consumption and GHG emissions, in addition to savings on maintenance and replacement cost.