Performance of Cpred/Cobs concentration ratios as a metric reflecting adherence to antidepressant drug therapy

Background: Nonadherence is very common among subjects undergoing pharmacotherapy for schizophrenia and depression. This study aimed to evaluate the performance of the ratio of the nonlinear mixed effects pharmacokinetic model predicted concentration to observed drug concentration (ratio of population predicted to observed concentration (Cpred/Cobs) and ratio of individual predicted to observed concentration (Cipred/Cobs) as a measure of erratic drug exposure, driven primarily by variable execution of the dosage regimen and unknown true dosage history. Methods: Modeling and simulation approaches in conjunction with dosage history information from the Medication Event Monitoring System (MEMS, provided by the "Depression: The search for treatment relevant phenotypes" study), was applied to evaluate the consistency of exposure via simulation studies with scenarios representing a long half-life drug (escitalopram). Adherence rates were calculated based on the percentage of the prescribed doses actually taken correctly during the treatment window of interest. The association between Cpred/Cobs, Cipred/Cobs ratio, and adherence rate was evaluated under various assumptions of known dosing history. Results: Simulations for those scenarios representing a known dosing history were generated from historical MEMS data. Simulations of a long half-life drug exhibited a trend for overprediction of concentrations in patients with a low percentage of doses taken and underprediction of concentrations in patients taking more than their prescribed number of doses. Overall, the ratios did not predict adherence well, except when the true adherence rates were extremely high (greater than 100% of prescribed doses) or extremely low (complete nonadherence). In general, the Cipred/Cobs ratio was a better predictor of adherence rate than the Cpred/Cobs ratio. Correct predictions of extreme (high, low) 7-day adherence rates using Cipred/Cobs were 73.8% and 64.0%. Conclusion: This simulation study demonstrated the limitations of the Cpred/obs and Cipred/obs ratios as metrics for actual dosage intake history, and identified that use of MEMS dosing history monitoring combined with sparse pharmacokinetic sampling is a more reliable approach. © 2011 Feng et al

Energy loss in perturbative QCD

We review the properties of energetic parton propagation in hot or cold QCD matter, as obtained in recent works. Advances in understanding the energy loss - collisional and radiative - are summarized, with emphasis on the latter: it features very interesting properties which may help to detect the quark-gluon plasma produced in heavy ion collisions. We describe two different theoretical approaches, which lead to the same radiated gluon energy spectrum. The case of a longitudinally expanding QCD plasma is investigated. The energy lost by a jet with given opening angle is calculated in view of making predictions for the suppression (quenching) of hard jet production. Phenomenological implications for the difference between hot and cold matter are discussed. Numerical estimates of the loss suggest that it may be significantly enhanced in hot compared to cold matter.Comment: 49 pages latex file with 11 embedded PS figures. Uses ar.sty (included), one equation revised. submitted to Annual Review of Nuclear and Particle Scienc

The small quinolone derived compound HT61 enhances the effect of tobramycin against Pseudomonas aeruginosa in vitro and in vivo.

HT61 is a small quinolone-derived compound previously demonstrated to exhibit bactericidal activity against gram-positive bacteria including methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). When combined with the classical antibiotics and antiseptics neomycin, gentamicin, mupirocin and chlorhexidine, HT61 demonstrated synergistic bactericidal activity against both MSSA and MRSA infections in vitro. In this study, we investigated the individual antimicrobial activity of HT61 alongside its capability to increase the efficacy of tobramycin against both a tobramycin sensitive laboratory reference strain (PAO1) and tobramycin resistant clinical isolates (RP73, NN2) of the gram-negative bacteria Pseudomonas aeruginosa (P. aeruginosa). Using broth microdilution methods, the MICs of HT61 against all strains were assessed, as well as the effect of HT61 in combination with tobramycin using both the chequerboard method and bacterial time-kill assays. A murine model of pulmonary infection was also used to evaluate the combination therapy of tobramycin and HT61 in vivo. In these studies, we demonstrated significant synergism between HT61 and Tobramycin against the tobramycin resistant P. aeruginosa strains RP73 and NN2, whilst an additive/intermediate effect was observed for P. aeruginosa strain PA01 which was further confirmed using bacterial time kill analysis. In addition, the enhancement of tobramycin by HT61 was also evident in in vitro assays of biofilm eradication. Finally, in vivo studies revealed analogous effects to those observed in vitro with HT61 when administered in combination with tobramycin against each of the three P. aeruginosa strains at the highest tested dose (10 mg/kg)

The STS-constructivist reform: some discordant notes

It would appear that as many more voices join in the advocacy for STS constructivist Reform in science teaching/learning, more discordant notes are emitted. The purpose of the paper therefore, was to spotlight some of these discordant notes emitted in the course of the on-going reform advocacy. Specifically, three of such discordant notes bordering on focus, status, and initiation of the reform are identified. After a critical examination of the seemingly conflicting views on these issues, and drawing from relevant underlying theoretical constructs, more rational, realistic and sustainable viewpoints are synthesized. African Journal of Educational Studies in Mathematics and Sciences Vol. 2(1) 2004: 19-2

The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies.

Feline infectious peritonitis (FIP) is a common and highly lethal coronavirus disease of domestic cats. Recent studies of diseases caused by several RNA viruses in people and other species indicate that antiviral therapy may be effective against FIP in cats. The small molecule nucleoside analog GS-441524 is a molecular precursor to a pharmacologically active nucleoside triphosphate molecule. These analogs act as an alternative substrate and RNA-chain terminator of viral RNA dependent RNA polymerase. We determined that GS-441524 was non-toxic in feline cells at concentrations as high as 100 uM and effectively inhibited FIPV replication in cultured CRFK cells and in naturally infected feline peritoneal macrophages at concentrations as low as 1 uM. We determined the pharmacokinetics of GS-441524 in cats in vivo and established a dosage that would sustain effective blood levels for 24 h. In an experimental FIPV infection of cats, GS-441524 treatment caused a rapid reversal of disease signs and return to normality with as little as two weeks of treatment in 10/10 cats and with no apparent toxicity

Factors and options for improved frequency regulation: Case study of utility scale solar in Nigeria

This paper presents the structure, tuning, and evaluation of a model for power system frequency response in Nigeria. We demonstrate that a 100MW utility scale solar farm is unlikely to degrade frequency performance, and we quantify the effect of several possible interventions to improve frequency regulation. The Nigerian system already experiences wide frequency variations due to steel mill loads and load rejection during storms, and this often necessitates manual intervention and load management. The model is one of several employed in grid-integration evaluations of proposed large utility-scale solar farms. The model is intended to support ongoing discussions on how grid code and market policies should specify ancillary services supplied by participants

Expandohedra: Modeling Structural Transitions of a Viral Capsid

Inspired by natural phenomena and mathematical theory this paper presents the development of a model, based on the dodecahedron, that visualizes the structural transition and expansion of a capsid (viral protein shell)

Analysis of orientation error of triaxial accelerometers on the assessment of energy expenditure

This paper investigates the effects of orientation error in the positioning of triaxial accelerometers on the assessment of energy expenditure. Four subjects walked on a treadmill at varying velocities ranging from 4km.h -1 to 5km.h-1. During each test, a triaxial accelerometer attached to the lower back at arbitrary orientations to record body accelerations. Energy expenditure was estimated by the sum of the integrals of the absolute value of accelerometer output from all the three measurement directions. Based on theoretical analysis and experimental observations, it is concluded that small orientation errors ( < 3° ) have no distinguishable effects on the estimation of energy expenditure. We propose an efficient method to compensate for larger orientation errors. The experimental results verified the effectiveness of this proposed compensation method. ©2005 IEEE

Nested Polytopes with Non-crystallographic Symmetry Induced by Projection

Inspired by the structures of viruses and fullerenes in biology and chemistry, we have recently developed a method to construct nested polyhedra and, more generally, nested polytopes in multi-dimensional geometry with non-crystallographic symmetry. In this paper we review these results, presenting them from a geometrical point of view. Examples and applications in science and design are discussed