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

Mercury emissions and stable isotopic compositions at Vulcano Island (Italy)

Sampling and analyses methods for determining the stable isotopic compositions of Hg in an active volcanic system were tested and optimized at the volcanic complex of Vulcano (Aeolian Islands, Italy). Condensed gaseous fumarole Hg(fum) T , plume gaseous elemental Hg(g) 0 and plume particulate Hg(p) II were obtained at fumaroles F0, F5, F11, and FA. The average total Hg emissions, based on HgT/SO2 in condensed fumarolic gases and plumes, range from 2.5 to 10.1 kg y−1, in agreement with published values [Ferrara, R., Mazzolai, B., Lanzillotta, E., Nucaro, E., Pirrone, N., 2000. Volcanoes as emission sources of atmospheric mercury in the Mediterranean Basin. Sci. Total Environ. 259(1–3), 115–121; Aiuppa, A., Bagnato, E., Witt, M.L.I., Mather, T.A., Parello, F., Pyle, D.M., Martin, R.S., 2007. Real-time simultaneous detection of volcanic Hg and SO2 at La Fossa Crater, Vulcano (Aeolian Islands, Sicily). Geophys. Res. Lett. 34(L21307).]. Plume Hg(p) II increases with distance from the fumarole vent, at the expense of Hg(g) 0 and indicates significant in-plume oxidation and condensation of fumarole Hg(fum) T . Relative to the NIST SRM3133 Hg standard, the stable isotopic compositions of Hg are δ202Hg(fum) T =−0.74‰±0.18 (2SD, n=4) for condensed gaseous fumarole Hg(fum) T , δ202Hg(g) 0 =−1.74‰±0.36 (2SD, n=1) for plume gaseous elemental Hg(g) 0 at the F0 fumarole, and δ202Hg(p) II =−0.11‰±0.18 (2SD, n=4) for plume particulate Hg(p) II . The enrichment of Hg(p) II in the heavy isotopes and Hg(g) 0 in the light isotopes relative to the total condensed fumarolic Hg(fum) T gas complements the speciation data and demonstrates a gas-particle fractionation occurring after the gas expulsion inambient T° atmosphere. A first order Rayleigh equilibriumcondensation isotope fractionation model yields a fractionation factor αcond-gas of 1.00135±0.00058

Exoplanets or Dynamic Atmospheres? The Radial Velocity and Line Shape Variations of 51 Pegasi and Tau Bootis

Because of our relatively low spectral resolution, we compare our observations with Gray's line bisector data by fitting observed line profiles to an expansion in terms of orthogonal (Hermite) functions. To obtain an accurate comparison, we model the emergent line profiles from rotating and pulsating stars, taking the instrumental point spread function into account. We describe this modeling process in detail. We find no evidence for line profile or strength variations at the radial velocity period in either 51 Peg or in Tau Boo. For 51 Peg, our upper limit for line shape variations with 4.23-day periodicity is small enough to exclude with 10 sigma confidence the bisector curvature signal reported by Gray & Hatzes; the bisector span and relative line depth signals reported by Gray (1997) are also not seen, but in this case with marginal (2 sigma) confidence. We cannot, however, exclude pulsations as the source of 51 Peg's radial velocity variation, because our models imply that line shape variations associated with pulsations should be much smaller than those computed by Gray & Hatzes; these smaller signals are below the detection limits both for Gray & Hatzes' data and for our own. Tau Boo's large radial velocity amplitude and v*sin(i) make it easier to test for pulsations in this star. Again we find no evidence for periodic line-shape changes, at a level that rules out pulsations as the source of the radial velocity variability. We conclude that the planet hypothesis remains the most likely explanation for the existing data.Comment: 44 pages, 19 figures, plain TeX, accepted to ApJS (companion to letter astro-ph/9712279

Pharmacokinetic/pharmacodynamic integration and modelling of florfenicol for the pig pneumonia pathogens Actinobacillus pleuropneumoniae and Pasteurella multocida

Pharmacokinetic-pharmacodynamic (PK/PD) integration and modelling were used to predict dosage schedules for florfenicol for two pig pneumonia pathogens, Actinobacillus pleuropneumoniae and Pasteurella multocida. Pharmacokinetic data were pooled for two bioequivalent products, pioneer and generic formulations, administered intramuscularly to pigs at a dose rate of 15 mg/kg. Antibacterial potency was determined in vitro as minimum inhibitory concentration (MIC) and Mutant Prevention Concentration in broth and pig serum, for six isolates of each organism. For both organisms and for both serum and broth MICs, average concentration:MIC ratios over 48 h were similar and exceeded 2.5:1 and times greater than MIC exceeded 35 h. From in vitro time-kill curves, PK/PD modelling established serum breakpoint values for the index AUC24h/MIC for three levels of inhibition of growth, bacteriostasis and 3 and 4log10 reductions in bacterial count; means were 25.7, 40.2 and 47.0 h, respectively, for P. multocida and 24.6, 43.8 and 58.6 h for A. pleuropneumoniae. Using these PK and PD data, together with literature MIC distributions, doses for each pathogen were predicted for: (1) bacteriostatic and bactericidal levels of kill; (2) for 50 and 90% target attainment rates (TAR); and (3) for single dosing and daily dosing at steady state. Monte Carlo simulations for 90% TAR predicted single doses to achieve bacteriostatic and bactericidal actions over 48 h of 14.4 and 22.2 mg/kg (P. multocida) and 44.7 and 86.6 mg/kg (A. pleuropneumoniae). For daily doses at steady state, and 90% TAR bacteriostatic and bactericidal actions, dosages of 6.2 and 9.6 mg/kg (P. multocida) and 18.2 and 35.2 mg/kg (A. pleuropneumoniae) were required. PK/PD integration and modelling approaches to dose determination indicate the possibility of tailoring dose to a range of end-points

Solar-like oscillations in the metal-poor subgiant nu Indi: II. Acoustic spectrum and mode lifetime

Convection in stars excites resonant acoustic waves which depend on the sound speed inside the star, which in turn depends on properties of the stellar interior. Therefore, asteroseismology is an unrivaled method to probe the internal structure of a star. We made a seismic study of the metal-poor subgiant star nu Indi with the goal of constraining its interior structure. Our study is based on a time series of 1201 radial velocity measurements spread over 14 nights obtained from two sites, Siding Spring Observatory in Australia and ESO La Silla Observatory in Chile. The power spectrum of the high precision velocity time series clearly presents several identifiable peaks between 200 and 500 uHz showing regularity with a large and small spacing of 25.14 +- 0.09 uHz and 2.96 +- 0.22 uHz at 330 uHz. Thirteen individual modes have been identified with amplitudes in the range 53 to 173 cm/s. The mode damping time is estimated to be about 16 days (1-sigma range between 9 and 50 days), substantially longer than in other stars like the Sun, the alpha Cen system or the giant xi Hya.Comment: 5 pages, 7 figures, A&A accepte

PHIL photoinjector test line

LAL is now equiped with its own platform for photoinjectors tests and Research and Developement, named PHIL (PHotoInjectors at LAL). This facility has two main purposes: push the limits of the photoinjectors performances working on both the design and the associated technology and provide a low energy (MeV) short pulses (ps) electron beam for the interested users. Another very important goal of this machine will be to provide an opportunity to form accelerator physics students, working in a high technology environment. To achieve this goal a test line was realised equipped with an RF source, magnets and beam diagnostics. In this article we will desrcibe the PHIL beamline and its characteristics together with the description of the first two photoinjector realised in LAL and tested: the ALPHAX and the PHIN RF Guns

Fourier Analysis of Gapped Time Series: Improved Estimates of Solar and Stellar Oscillation Parameters

Quantitative helio- and asteroseismology require very precise measurements of the frequencies, amplitudes, and lifetimes of the global modes of stellar oscillation. It is common knowledge that the precision of these measurements depends on the total length (T), quality, and completeness of the observations. Except in a few simple cases, the effect of gaps in the data on measurement precision is poorly understood, in particular in Fourier space where the convolution of the observable with the observation window introduces correlations between different frequencies. Here we describe and implement a rather general method to retrieve maximum likelihood estimates of the oscillation parameters, taking into account the proper statistics of the observations. Our fitting method applies in complex Fourier space and exploits the phase information. We consider both solar-like stochastic oscillations and long-lived harmonic oscillations, plus random noise. Using numerical simulations, we demonstrate the existence of cases for which our improved fitting method is less biased and has a greater precision than when the frequency correlations are ignored. This is especially true of low signal-to-noise solar-like oscillations. For example, we discuss a case where the precision on the mode frequency estimate is increased by a factor of five, for a duty cycle of 15%. In the case of long-lived sinusoidal oscillations, a proper treatment of the frequency correlations does not provide any significant improvement; nevertheless we confirm that the mode frequency can be measured from gapped data at a much better precision than the 1/T Rayleigh resolution.Comment: Accepted for publication in Solar Physics Topical Issue "Helioseismology, Asteroseismology, and MHD Connections

Toxicokinetics of bisphenol-S and its glucuronide in plasma and urine following oral and dermal exposure in volunteers for the interpretation of biomonitoring data

The measurement of bisphenol-S (BPS) and its glucurono-conjugate (BPSG) in urine may be used for the biomonitoring of exposure in populations. However, this requires a thorough knowledge of their toxicokinetics. The time courses of BPS and BPSG were assessed in accessible biological matrices of orally and dermally exposed volunteers. Under the approval of the Research Ethics Committee of the University of Montreal, six volunteers were orally exposed to a BPS-d8 deuterated dose of 0.1 mg/kg body weight (bw). One month later, 1 mg/kg bw of BPS-d8 were applied on 40 cm2 of the forearm and then washed 6 h after application. Blood samples were taken prior to dosing and at fixed time periods over 48 h after treatment; complete urine voids were collected pre-exposure and at pre-established intervals over 72 h postdosing. Following oral exposure, the plasma concentration–time courses of BPS-d8 and BPSG-d8 over 48 h evolved in parallel, and showed a rapid appearance and elimination. Average peak values (±SD) were reached at 0.7 ± 0.1 and 1.1 ± 0.4 h postdosing and mean (±SD) apparent elimination half-lives (t½) of 7.9 ± 1.1 and 9.3 ± 7.0 h were calculated from the terminal phase of BPS-d8 and BPSG-d8 in plasma, respectively. The fraction of BPS-d8 reaching the systemic circulation unchanged (i.e. bioavailability) was further estimated at 62 ± 5% on average (±SD) and the systemic plasma clearance at 0.57 ± 0.07 L/kg bw/h. Plasma concentration–time courses and urinary excretion rate profiles roughly evolved in parallel for both substances, as expected. The average percent (±SD) of the administered dose recovered in urine as BPS-d8 and BPSG-d8 over the 0–72 h period postdosing was 1.72 ± 1.3 and 54 ± 10%. Following dermal application, plasma levels were under the lower limit of quantification (LLOQ) at most time points. However, peak values were reached between 5 and 8 h depending on individuals, suggesting a slower absorption rate compared to oral exposure. Similarly, limited amounts of BPS-d8 and its conjugate were recovered in urine and peak excretion rates were reached between 5 and 11 h postdosing. The average percent (±SD) of the administered dose recovered in urine as BPS-d8 and BPSG-d8 was about 0.004 ± 0.003 and 0.09 ± 0.07%, respectively. This study provided greater precision on the kinetics of this contaminant in humans and, in particular, evidenced major differences between BPA and BPS kinetics with much higher systemic levels of active BPS than BPA, an observation explained by a higher oral bioavailability of BPS than BPA. These data should also be useful in developing a toxicokinetic model for a better interpretation of biomonitoring data

The non-detection of oscillations in Procyon by MOST: is it really a surprise?

We argue that the non-detection of oscillations in Procyon by the MOST satellite reported by Matthews et al. (2004) is fully consistent with published ground-based velocity observations of this star. We also examine the claims that the MOST observations represent the best photometric precision so far reported in the literature by about an order of magnitude and are the most sensitive data set for asteroseismology available for any star other than the Sun. These statements are not correct, with the most notable exceptions being observations of oscillations in alpha Cen A that are far superior. We further disagree that the hump of excess power seen repeatedly from velocity observations of Procyon can be explained as an artefact caused by gaps in the data. The MOST observations failed to reveal oscillations clearly because their noise level is too high, possibly from scattered Earthlight in the instrument. We did find an excess of strong peaks in the MOST amplitude spectrum that is inconsistent with a simple noise source such as granulation, and may perhaps indicate oscillations at roughly the expected level.Comment: 6 pages, accepted for publication in A&A Letter

The quest for the solar g modes

Solar gravity modes (or g modes) -- oscillations of the solar interior for which buoyancy acts as the restoring force -- have the potential to provide unprecedented inference on the structure and dynamics of the solar core, inference that is not possible with the well observed acoustic modes (or p modes). The high amplitude of the g-mode eigenfunctions in the core and the evanesence of the modes in the convection zone make the modes particularly sensitive to the physical and dynamical conditions in the core. Owing to the existence of the convection zone, the g modes have very low amplitudes at photospheric levels, which makes the modes extremely hard to detect. In this paper, we review the current state of play regarding attempts to detect g modes. We review the theory of g modes, including theoretical estimation of the g-mode frequencies, amplitudes and damping rates. Then we go on to discuss the techniques that have been used to try to detect g modes. We review results in the literature, and finish by looking to the future, and the potential advances that can be made -- from both data and data-analysis perspectives -- to give unambiguous detections of individual g modes. The review ends by concluding that, at the time of writing, there is indeed a consensus amongst the authors that there is currently no undisputed detection of solar g modes.Comment: 71 pages, 18 figures, accepted by Astronomy and Astrophysics Revie