On deriving p-mode parameters for inclined solar-like stars

Thanks to their high quality, new and upcoming asteroseismic observations - with CoRoT, Kepler, and from the ground... - can benefit from the experience gained with helioseismology. We focus in this paper on solar-like oscillations, for which the inclination of the rotation axis is unknown. We present a theoretical study of the errors of p-mode parameters determined by means of a maximum-likelihood estimator, and we also analyze correlations and biases. We have used different, complementary approaches: we have performed either semi-analytical computation of the Hessian matrix, fitting of single mean profiles, or Monte Carlo simulations. We give first analytical approximations for the errors of frequency, inclination and rotational splitting. The determination of the inclination is very challenging for the common case of slow rotators (like the Sun), making difficult the determination of a reliable rotational splitting. Moreover, due to the numerous correlations, biases - more or less significant - can appear in the determination of various parameters in the case of bad inclination fittings, especially when a locking at 90 degrees occurs. This issue concerning inclination locking is also discussed. Nevertheless, the central frequency and some derived parameters such as the total power of the mode are free of such biases.Comment: 9 pages, 6 figures, to appear in A&

Pharmacokinetic–pharmacodynamic integration and modelling of oxytetracycline for the calf pathogens Mannheimia haemolytica and Pasteurella multocida

A calf tissue cage model was used to study the pharmacokinetics (PK) and pharmacodynamics (PD) of oxytetracycline in serum, inflamed (exudate) and noninflamed (transudate) tissue cage fluids. After intramuscular administration, the PK was characterized by a long mean residence time of 28.3 hr. Based on minimum inhibitory concentrations (MICs) for six isolates each of Mannheimia haemolytica and Pasteurella multocida, measured in serum, integration of in vivo PK and in vitro PD data established area under serum concentration–time curve (AUC0–∞)/MIC ratios of 30.0 and 24.3 hr for M. haemolytica and P. multocida, respectively. Corresponding AUC0–∞/MIC ratios based on MICs in broth were 656 and 745 hr, respectively. PK-PD modelling of in vitro bacterial time–kill curves for oxytetracycline in serum established mean AUC0–24 hr/MIC ratios for 3log10 decrease in bacterial count of 27.5 hr (M. haemolytica) and 60.9 hr (P. multocida). Monte Carlo simulations predicted target attainment rate (TAR) dosages. Based on the potency of oxytetracycline in serum, the predicted 50% TAR single doses required to achieve a bacteriostatic action covering 48-hr periods were 197 mg/kg (M. haemolytica) and 314 mg/kg (P. multocida), respectively, against susceptible populations. Dosages based on the potency of oxytetracycline in broth were 25- and 27-fold lower (7.8 and 11.5 mg/kg) for M. haemolytica and P. multocida, respectively

Pharmacokinetic/pharmacodynamic integration and modelling of oxytetracycline for the porcine pneumonia pathogens Actinobacillus pleuropneumoniae and Pasteurella multocida

Pharmacokinetic–pharmacodynamic (PK/PD) integration and modelling were used to predict dosage schedules of oxytetracycline for two pig pneumonia pathogens, Actinobacillus pleuropneumoniae and Pasteurella multocida. Minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) were determined in broth and porcine serum. PK/PD integration established ratios of average concentration over 48 h (Cav0–48 h)/MIC of 5.87 and 0.27 µg/mL (P. multocida) and 0.70 and 0.85 µg/mL (A. pleuropneumoniae) for broth and serum MICs, respectively. PK/PD modelling of in vitro time–kill curves established broth and serum breakpoint values for area under curve (AUC0–24 h)/MIC for three levels of inhibition of growth, bacteriostasis and 3 and 4 log10 reductions in bacterial count. Doses were then predicted for each pathogen, based on Monte Carlo simulations, for: (i) bacteriostatic and bactericidal levels of kill; (ii) 50% and 90% target attainment rates (TAR); and (iii) single dosing and daily dosing at steady-state. For 90% TAR, predicted daily doses at steady-state for bactericidal actions were 1123 mg/kg (P. multocida) and 43 mg/kg (A. pleuropneumoniae) based on serum MICs. Lower TARs were predicted from broth MIC data; corresponding dose estimates were 95 mg/kg (P. multocida) and 34 mg/kg (A. pleuropneumoniae)

Modeling of Large Pharmacokinetic Data Using Nonlinear Mixed-Effects: A Paradigm Shift in Veterinary Pharmacology. A Case Study With Robenacoxib in Cats

The objective of this study was to model the pharmacokinetics (PKs) of robenacoxib in cats using a nonlinear mixed‐effects (NLME) approach, leveraging all available information collected from cats receiving robenacoxib s.c. and/or i.v.: 47 densely sampled laboratory cats and 36 clinical cats sparsely sampled preoperatively. Data from both routes were modeled sequentially using Monolix 4.3.2. Influence of parameter correlations and available covariates (age, gender, bodyweight, and anesthesia) on population parameter estimates were evaluated by using multiple samples from the posterior distribution of the random effects. A bicompartmental disposition model with simultaneous zero and first‐order absorption best described robenacoxib PKs in blood. Clearance was 0.502 L/kg/h and the bioavailability was high (78%). The absorption constant point estimate (Ka = 0.68 h−1) was lower than beta (median, 1.08 h−1), unveiling flip‐flop kinetics. No dosing adjustment based on available covariates information is advocated. This modeling work constitutes the first application of NLME in a large feline population

Comparison of standardised versus non-standardised methods for testing the in vitro potency of oxytetracycline against mannheimia haemolytica and pasteurella multocida

The in vitro pharmacodynamics of oxytetracycline was established for six isolates of each of the calf pneumonia pathogens Mannheimia haemolytica and Pasteurella multocida. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and bacterial time-kill curves were determined in two matrices, Mueller Hinton broth (MHB) and calf serum. Geometric mean MIC ratios, serum:MHB, were 25.2:1 (M. haemolytica) and 27.4:1 (P. multocida). The degree of binding of oxytetracycline to serum protein was 52.4%. Differences between serum and broth MICs could not be accounted for by oxytetracycline binding to serum protein. In vitro time-kill data suggested a co-dependent killing action of oxytetracycline. The in vitro data indicate inhibition of the killing action of oxytetracycline by serum factor(s). The nature of the inhibition requires further study. The outcome of treatment with oxytetracycline of respiratory tract infections in calves caused by M. haemolytica and P. multocida may not be related solely to a direct killing action

Un món de mones. La persistència de Robert Robert

Cada vegada que es tornen a llegir els vint-i-set articles que Robert Robert va publicar al setmanari Un tros de paper entre el 1865 i el 1866, es constata fins a quin punt és certa la coneguda afirmació de Josep Pla segons la qual alguns d’aquests textos —i en particular el titulat La rebotiga— són de les millors coses escrites en català durant la Reinaxença. Si deixem Verdaguer al marge, els articles de Robert són efectivament els únics textos del seu temps que encara val la pena llegir; i deixar Verdaguer al marge és justament el que fa Pla per construir el seu elogi. És a dir, decideix que tenen més interès un grapadet d’escrits humorístics destinats a entretenir els barcelonins el diumenge a la tarda, que no pas una obra d’abast espiritual, ambiciosa i extensa com la de Verdaguer. Per si aquestes circumstàncies no fessin encara prou escandalosa la preferència de Pla, la llengua amb què treballa Robert és d’entrada un material rovellat, carregat de llacunes d’imperfeccions, i que no té per model sinó el que l’orella pot captar sobre la marxa a les converses ordinàries dels ciutadans. Verdaguer, en canvi, que també es veu obligat a modelar el català literari sobre la base del que sent dir, posseeix un coneixement profund de la parla dels pagesos de la Plana de Vic, molt menys contaminada que la de Barcelona, i un instint pel llenguatge poètic que fa de la seva obra un dels fonaments més segurs de la literatura catalana moderna. Com no podria ser d’altra manera, Pla reconeix aquesta realitat, però al final en conclou que “per al gust d’avui són molt més interessants les descripcions vulgars de Robert que les retòricament tòpiques de Verdaguer”

Cultura contra cultura

De totes les grans paraules, és a dir, de tots els vocables destinats a la confusió, cultura és amb força probabilitat la que ha sofert les més grans expropiacions. Procedent del mot llatí cultus, participi de colere, va designar en primer lloc el conreu de la terra, i amb el concepte de cultura animi de Ciceró es va obrir al conreu de l’esperit, al creixement de les facultats morals per la via de l’educació, l’experiència i la lectura dels grans autors

Standard PK/PD concepts can be applied to determine a dosage regimen for a macrolide: the case of tulathromycin in the calf

The pharmacokinetic (PK) profile of tulathromycin, administered to calves subcutaneously at the dosage of 2.5 mg/kg, was established in serum, inflamed (exudate), and noninflamed (transudate) fluids in a tissue cage model. The PK profile of tulathromycin was also established in pneumonic calves. For Mannheimia haemolytica and Pasteurella multocida, tulathromycin minimum inhibitory concentrations (MIC) were approximately 50 times lower in calf serum than in Mueller–Hinton broth. The breakpoint value of the PK/pharmacodynamic (PD) index (AUC(0–24 h)/MIC) to achieve a bactericidal effect was estimated from in vitro time‐kill studies to be approximately 24 h for M. haemolytica and P. multocida. A population model was developed from healthy and pneumonic calves and, using Monte Carlo simulations, PK/PD cutoffs required for the development of antimicrobial susceptibility testing (AST) were determined. The population distributions of tulathromycin doses were established by Monte Carlo computation (MCC). The computation predicted a target attainment rate (TAR) for a tulathromycin dosage of 2.5 mg/kg of 66% for M. haemolytica and 87% for P. multocida. The findings indicate that free tulathromycin concentrations in serum suffice to explain the efficacy of single‐dose tulathromycin in clinical use, and that a dosage regimen can be computed for tulathromycin using classical PK/PD concepts