Simultaneous Determination of Human Plasma Levels of Citalopram, Paroxetine, Sertraline, and Their Metabolites by Gas Chromatography—Mass Spectrometry

A gas chromatography—mass spectrometry method is presented which allows the simultaneous determination of the plasma concentrations of the selective serotonin reuptake inhibitors citalopram, paroxetine, sertraline, and their pharmacologically active N-demethylated metabolites (desmethylcitalopram, didesmethylcitalopram, and desmethylsertraline) after derivatization with the reagent N-methyl-bis(trifluoroacetamide). No interferences from endogenous compounds are observed following the extraction of plasma samples from six different human subjects. The standard curves are linear over a working range of 10-500 ng/mL for citalopram, 10-300 ng/mL for desmethylcitalopram, 5-60 ng/mL for didesmethylcitalopram, 20-400 ng/mL for sertraline and desmethylsertraline, and 10-200 ng/mL for paroxetine. Recoveries measured at three concentrations range from 81 to 118% for the tertiary amines (citalopram and the internal standard methylmaprotiline), 73 to 95% for the secondary amines (desmethylcitalopram, paroxetine and sertraline), and 39 to 66% for the primary amines (didesmethylcitalopram and desmethylsertraline). Intra- and interday coefficients of variation determined at three concentrations range from 3 to 11 % for citalopram and its metabolites, 4 to 15% for paroxetine, and 5 to 13% for sertraline and desmethylsertraline. The limits of quantitation of the method are 2 ng/mL for citalopram and paroxetine, 1 ng/mL for sertraline, and 0.5 ng/mL for desmethylcitalopram, didesmethylcitalopram, and desmethylsertraline. No interferences are noted from 20 other psychotropic drugs. This sensitive and specific method can be used for single-dose pharmacokinetics. It is also useful for therapeutic drug monitoring of these three drugs and could possibly be adapted for the quantitation of the two other selective serotonin reuptake inhibitors on the market, namely fluoxetine and fluvoxamin

Crack-Like Processes Governing the Onset of Frictional Slip

We perform real-time measurements of the net contact area between two blocks of like material at the onset of frictional slip. We show that the process of interface detachment, which immediately precedes the inception of frictional sliding, is governed by three different types of detachment fronts. These crack-like detachment fronts differ by both their propagation velocities and by the amount of net contact surface reduction caused by their passage. The most rapid fronts propagate at intersonic velocities but generate a negligible reduction in contact area across the interface. Sub-Rayleigh fronts are crack-like modes which propagate at velocities up to the Rayleigh wave speed, VR, and give rise to an approximate 10% reduction in net contact area. The most efficient contact area reduction (~20%) is precipitated by the passage of slow detachment fronts. These fronts propagate at anomalously slow velocities, which are over an order of magnitude lower than VR yet orders of magnitude higher than other characteristic velocity scales such as either slip or loading velocities. Slow fronts are generated, in conjunction with intersonic fronts, by the sudden arrest of sub-Rayleigh fronts. No overall sliding of the interface occurs until either of the slower two fronts traverses the entire interface, and motion at the leading edge of the interface is initiated. Slip at the trailing edge of the interface accompanies the motion of both the slow and sub-Rayleigh fronts. We might expect these modes to be important in both fault nucleation and earthquake dynamics.Comment: 19 page, 5 figures, to appear in International Journal of Fractur

Uniform Selection as a Primary Force Reducing Population Genetic Differentiation of Cavitation Resistance across a Species Range

Background: Cavitation resistance to water stress-induced embolism determines plant survival during drought. This adaptive trait has been described as highly variable in a wide range of tree species, but little is known about the extent of genetic and phenotypic variability within species. This information is essential to our understanding of the evolutionary forces that have shaped this trait, and for evaluation of its inclusion in breeding programs. Methodology: We assessed cavitation resistance (P 50), growth and carbon isotope composition in six Pinus pinaster populations in a provenance and progeny trial. We estimated the heritability of cavitation resistance and compared the distribution of neutral markers (FST) and quantitative genetic differentiation (QST), for retrospective identification of the evolutionary forces acting on these traits. Results/Discussion: In contrast to growth and carbon isotope composition, no population differentiation was found for cavitation resistance. Heritability was higher than for the other traits, with a low additive genetic variance (h 2 ns = 0.4360.18, CVA = 4.4%). QST was significantly lower than FST, indicating uniform selection for P50, rather than genetic drift. Putativ

Quantifying in situ phenotypic variability in the hydraulic properties of four tree species across their distribution range in Europe

Many studies have reported that hydraulic properties vary considerably between tree species, but little is known about their intraspecific variation and, therefore, their capacity to adapt to a warmer and drier climate. Here, we quantify phenotypic divergence and clinal variation for embolism resistance, hydraulic conductivity and branch growth, in four tree species, two angiosperms (Betula pendula, Populus tremula) and two conifers (Picea abies, Pinus sylvestris), across their latitudinal distribution in Europe. Growth and hydraulic efficiency varied widely within species and between populations. The variability of embolism resistance was in general weaker than that of growth and hydraulic efficiency, and very low for all species but Populus tremula. In addition, no and weak support for a safety vs. efficiency trade-off was observed for the angiosperm and conifer species, respectively. The limited variability of embolism resistance observed here for all species except Populus tremula, suggests that forest populations will unlikely be able to adapt hydraulically to drier conditions through the evolution of embolism resistance.Peer reviewe

Weak tradeoff between xylem safety and xylem-specific hydraulic efficiency across the world\u27s woody plant species.

The evolution of lignified xylem allowed for the efficient transport of water under tension, but also exposed the vascular network to the risk of gas emboli and the spread of gas between xylem conduits, thus impeding sap transport to the leaves. A well-known hypothesis proposes that the safety of xylem (its ability to resist embolism formation and spread) should trade off against xylem efficiency (its capacity to transport water). We tested this safety-efficiency hypothesis in branch xylem across 335 angiosperm and 89 gymnosperm species. Safety was considered at three levels: the xylem water potentials where 12%, 50% and 88% of maximal conductivity are lost. Although correlations between safety and efficiency were weak (r(2) \u3c 0.086), no species had high efficiency and high safety, supporting the idea for a safety-efficiency tradeoff. However, many species had low efficiency and low safety. Species with low efficiency and low safety were weakly associated (r(2) \u3c 0.02 in most cases) with higher wood density, lower leaf- to sapwood-area and shorter stature. There appears to be no persuasive explanation for the considerable number of species with both low efficiency and low safety. These species represent a real challenge for understanding the evolution of xylem

Photon-Photon Physics in Very Peripheral Collisions of Relativistic Heavy Ions

In central collisions at relativistic heavy ion colliders like the Relativistic Heavy Ion Collider RHIC/Brookhaven and the Large Hadron Collider LHC (in its heavy ion mode) at CERN/Geneva, one aims at detecting a new form of hadronic matter - the Quark Gluon Plasma. It is the purpose of this review to discuss a complementary aspect of these collisions, the very peripheral ones. Due to coherence, there are strong electromagnetic fields of short duration in such collisions. They give rise to photon-photon and photon-nucleus collisions with high flux up to an invariant mass region hitherto unexplored experimentally. After a general survey photon-photon luminosities in relativistic heavy ion collisions are discussed. Special care is taken to include the effects of strong interactions and nuclear size. Then photon-photon physics at various gamma-gamma-invariant mass scales is discussed. The region of several GeV, relevant for RHIC is dominated by QCD phenomena (meson and vector meson pair production). Invariant masses of up to about 100 GeV can be reached at LHC, and the potential for new physics is discussed. Photonuclear reactions and other important background effects, especially diffractive processes are also discussed. A special chapter is devoted to lepton-pair production, especially electron-positron pair production; due to the strong fields new phenomena, especially multiple e+-e- pair production, will occur there.Comment: 40 pages, 19 figures, Topical Review, to appear in Journal of Physics G, revised text, updated text/references, one figure replace

Statistical properties of seismicity of fault zones at different evolutionary stages

We perform a systematic parameter space study of the seismic response of a large fault with different levels of heterogeneity, using a 3-D elastic framework within the continuum limit. The fault is governed by rate-and-state friction and simulations are performed for model realizations with frictional and large scale properties characterized by different ranges of size scales. We use a number of seismicity and stress functions to characterize different types of seismic responses and test the correlation between hypocenter locations and the employed distributions of model parameters. The simulated hypocenters are found to correlate significantly with small L values of the rate-and-state friction. The final sizes of earthquakes are correlated with physical properties at their nucleation sites. The obtained stacked scaling relations are overall self-similar and have good correspondence with properties of natural earthquakes