Stability of Propofol (2,6-Diisopropylphenol) in Thermal Desorption Tubes during Air Transport

The anesthetic propofol and other exhaled organic compounds can be sampled in Tenax sorbent tubes and analyzed by gas chromatography coupled with mass spectrometry. The aim of this study was to evaluate the stability of propofol in Tenax sorbent tubes during overseas shipping. This is relevant for international pharmacokinetic studies on propofol in exhaled air. Tenax sorbent tube propofol samples with concentrations between 10 and 100 ng were prepared by liquid injection and with a calibration gas generator. For each preparation method, one reference set was analyzed immediately after preparation, a second set was stored at room temperature, and a third one was stored refrigerated. The fourth set was sent from Germany by airmail to USA and back. The shipped set of tubes was analyzed when it returned after 55 days elapsed. Then, the room temperature samples and the refrigerated stored samples were also analyzed. To evaluate the stability of propofol in the stored and shipped tubes, we calculated the recovery rates of each sample set. The mean recovery in the stored samples was 101.2% for the liquid preparation and 134.6% for the gaseous preparation at 4°C. At 22°C, the recovery was 96.1% for liquid preparation and 92.1% for gaseous preparation, whereas the shipped samples had a recovery of 85.3% and 111.3%. Thus, the deviation of the shipped samples is within a range of 15%, which is analytically acceptable. However, the individual values show significantly larger deviations of up to -32.1% (liquid) and 30.9% (gaseous). We conclude that storage of propofol on Tenax tubes at room temperature for 55 days is possible to obtain acceptable results. However, it appears that due to severe temperature and pressure variations air shipment of propofol samples in Tenax tubes without cooling shows severe deviations from the initial concentration. Although it was not tested in this study, we assume that refrigerated transport might be necessary to obtain comparable results as in the stored samples

Stability of Propofol (2,6-Diisopropylphenol) in Thermal Desorption Tubes during Air Transport

The anesthetic propofol and other exhaled organic compounds can be sampled in Tenax sorbent tubes and analyzed by gas chromatography coupled with mass spectrometry. The aim of this study was to evaluate the stability of propofol in Tenax sorbent tubes during overseas shipping. This is relevant for international pharmacokinetic studies on propofol in exhaled air. Tenax sorbent tube propofol samples with concentrations between 10 and 100 ng were prepared by liquid injection and with a calibration gas generator. For each preparation method, one reference set was analyzed immediately after preparation, a second set was stored at room temperature, and a third one was stored refrigerated. The fourth set was sent from Germany by airmail to USA and back. The shipped set of tubes was analyzed when it returned after 55 days elapsed. Then, the room temperature samples and the refrigerated stored samples were also analyzed. To evaluate the stability of propofol in the stored and shipped tubes, we calculated the recovery rates of each sample set. The mean recovery in the stored samples was 101.2% for the liquid preparation and 134.6% for the gaseous preparation at 4°C. At 22°C, the recovery was 96.1% for liquid preparation and 92.1% for gaseous preparation, whereas the shipped samples had a recovery of 85.3% and 111.3%. Thus, the deviation of the shipped samples is within a range of 15%, which is analytically acceptable. However, the individual values show significantly larger deviations of up to -32.1% (liquid) and 30.9% (gaseous). We conclude that storage of propofol on Tenax tubes at room temperature for 55 days is possible to obtain acceptable results. However, it appears that due to severe temperature and pressure variations air shipment of propofol samples in Tenax tubes without cooling shows severe deviations from the initial concentration. Although it was not tested in this study, we assume that refrigerated transport might be necessary to obtain comparable results as in the stored samples

Quantification of Volatile Aldehydes Deriving from In Vitro Lipid Peroxidation in the Breath of Ventilated Patients

Exhaled aliphatic aldehydes were proposed as non-invasive biomarkers to detect increased lipid peroxidation in various diseases. As a prelude to clinical application of the multicapillary column–ion mobility spectrometry for the evaluation of aldehyde exhalation, we, therefore: (1) identified the most abundant volatile aliphatic aldehydes originating from in vitro oxidation of various polyunsaturated fatty acids; (2) evaluated emittance of aldehydes from plastic parts of the breathing circuit; (3) conducted a pilot study for in vivo quantification of exhaled aldehydes in mechanically ventilated patients. Pentanal, hexanal, heptanal, and nonanal were quantifiable in the headspace of oxidizing polyunsaturated fatty acids, with pentanal and hexanal predominating. Plastic parts of the breathing circuit emitted hexanal, octanal, nonanal, and decanal, whereby nonanal and decanal were ubiquitous and pentanal or heptanal not being detected. Only pentanal was quantifiable in breath of mechanically ventilated surgical patients with a mean exhaled concentration of 13 ± 5 ppb. An explorative analysis suggested that pentanal exhalation is associated with mechanical power—a measure for the invasiveness of mechanical ventilation. In conclusion, exhaled pentanal is a promising non-invasive biomarker for lipid peroxidation inducing pathologies, and should be evaluated in future clinical studies, particularly for detection of lung injury

Origin of the quasi-quantized Hall effect in ZrTe5

The quantum Hall effect (QHE) is traditionally considered a purely two-dimensional (2D) phenomenon. Recently, a three-dimensional (3D) version of the QHE has been reported in the Dirac semimetal ZrTe5. It was proposed to arise from a magnetic-field-driven Fermi surface instability, transforming the original 3D electron system into a stack of 2D sheets. Here, we report thermodynamic, thermoelectric and charge transport measurements on ZrTe5 in the quantum Hall regime. The measured thermodynamic properties: magnetization and ultrasound propagation, show no signatures of a Fermi surface instability, consistent with in-field single crystal X-ray diffraction. Instead, a direct comparison of the experimental data with linear response calculations based on an effective 3D Dirac Hamiltonian suggests that the quasi-quantization of the observed Hall response is an intrinsic property of the 3D electronic structure. Our findings render the Hall effect in ZrTe5 a truly 3D counterpart of the QHE in 2D systems

Pollinator movement activity influences genetic diversity and differentiation of spatially isolated populations of clonal forest herbs

In agricultural landscapes, forest herbs live in small, spatially isolated forest patches. For their long-term survival, their populations depend on animals as genetic linkers that provide pollen- or seed-mediated gene flow among different forest patches. However, whether insect pollinators serve as genetic linkers among spatially isolated forest herb populations in agricultural landscapes remains to be shown. Here, we used population genetic methods to analyze: (A) the genetic diversity and genetic differentiation of populations of two common, slow-colonizing temperate forest herb species [Polygonatum multiflorum (L.) All. and Anemone nemorosa L.] in spatially isolated populations within three agricultural landscapes in Germany and Sweden and (B) the movement activity of their most relevant associated pollinator species, i.e., the bumblebee Bombus pascuorum (Scopoli, 1,763) and the hoverfly Melanostoma scalare (Fabricus, 1,794), respectively, which differ in their mobility. We tested whether the indicated pollinator movement activity affected the genetic diversity and genetic differentiation of the forest herb populations. Bumblebee movement indicators that solely indicated movement activity between the forest patches affected both genetic diversity and genetic differentiation of the associated forest herb P. multiflorum in a way that can be explained by pollen-mediated gene flow among the forest herb populations. In contrast, movement indicators reflecting the total movement activity at a forest patch (including within-forest patch movement activity) showed unexpected effects for both plant-pollinator pairs that might be explained by accelerated genetic drift due to enhanced sexual reproduction. Our integrated approach revealed that bumblebees serve as genetic linkers of associated forest herb populations, even if they are more than 2 km apart from each other. No such evidence was found for the forest associated hoverfly species which showed significant genetic differentiation among forest patches itself. Our approach also indicated that a higher within-forest patch movement activity of both pollinator species might enhance sexual recruitment and thus diminishes the temporal buffer that clonal growth provides against habitat fragmentation effects

The use of error-category mapping in pharmacokinetic model analysis of dynamic contrast-enhanced MRI data.

This study introduces the use of 'error-category mapping' in the interpretation of pharmacokinetic (PK) model parameter results derived from dynamic contrast-enhanced (DCE-) MRI data. Eleven patients with metastatic renal cell carcinoma were enrolled in a multiparametric study of the treatment effects of bevacizumab. For the purposes of the present analysis, DCE-MRI data from two identical pre-treatment examinations were analysed by application of the extended Tofts model (eTM), using in turn a model arterial input function (AIF), an individually-measured AIF and a sample-average AIF. PK model parameter maps were calculated. Errors in the signal-to-gadolinium concentration ([Gd]) conversion process and the model-fitting process itself were assigned to category codes on a voxel-by-voxel basis, thereby forming a colour-coded 'error-category map' for each imaged slice. These maps were found to be repeatable between patient visits and showed that the eTM converged adequately in the majority of voxels in all the tumours studied. However, the maps also clearly indicated sub-regions of low Gd uptake and of non-convergence of the model in nearly all tumours. The non-physical condition ve ≥ 1 was the most frequently indicated error category and appeared sensitive to the form of AIF used. This simple method for visualisation of errors in DCE-MRI could be used as a routine quality-control technique and also has the potential to reveal otherwise hidden patterns of failure in PK model applications.This work was supported by GlaxoSmithKline UK, Wellcome Trust, Cambridge NIHR Biomedical Research Centre, Cambridge Experimental Cancer Medicine Centre, Cancer Research UKThis is the published version. It first appeared at http://www.sciencedirect.com/science/article/pii/S0730725X1400321X

Conductance Increase by Electron-Phonon Interaction in Quantum Wires

We investigate the influence of electron-phonon interactions on the DC-conductance $\Gamma$ of a quantum wire in the limit of one occupied subband. At zero temperature, a Tomonaga-Luttinger-like renormalization of $\Gamma$ to a value slightly larger than $2e^{2}/h$ is calculated for a realistic quantum wire model.Comment: 12 pages RevTeX, no figure. Appears in Phys. Rev.

Electrochemistry and Spin-Crossover Behavior of Fluorinated Terpyridine-Based Co(II) and Fe(II) Complexes

Due to their ability to form stable molecular complexes that have tailor-made properties, terpyridine ligands are of great interest in chemistry and material science. In this regard, we prepared two terpyridine ligands with two different fluorinated phenyl rings on the backbone. The corresponding CoII and FeII complexes were synthesized and characterized by single-crystal X-ray structural analysis, electrochemistry and temperature-dependent SQUID magnetometry. Single crystal X-ray diffraction analyses at 100 K of these complexes revealed Co−N and Fe−N bond lengths that are typical of low spin CoII and FeII centers. The metal centers are coordinated in an octahedral fashion and the fluorinated phenyl rings on the backbone are twisted out of the plane of the terpyridine unit. The complexes were investigated with cyclic voltammetry and UV/Vis-NIR spectroelectrochemistry. All complexes show a reversible oxidation and several reduction processes. Temperature dependent SQUID magnetometry revealed a gradual thermal SCO behavior in two of the complexes, while EPR spectroscopy provided further insights on the electronic structure of the metal complexes, as well as site of reduction

Stimulus - response curves of a neuronal model for noisy subthreshold oscillations and related spike generation

We investigate the stimulus-dependent tuning properties of a noisy ionic conductance model for intrinsic subthreshold oscillations in membrane potential and associated spike generation. On depolarization by an applied current, the model exhibits subthreshold oscillatory activity with occasional spike generation when oscillations reach the spike threshold. We consider how the amount of applied current, the noise intensity, variation of maximum conductance values and scaling to different temperature ranges alter the responses of the model with respect to voltage traces, interspike intervals and their statistics and the mean spike frequency curves. We demonstrate that subthreshold oscillatory neurons in the presence of noise can sensitively and also selectively be tuned by stimulus-dependent variation of model parameters.Comment: 19 pages, 7 figure

Enhancing bacteriophage therapeutics through in situ production and release of heterologous antimicrobial effectors

Bacteriophages operate via pathogen-specific mechanisms of action distinct from conventional, broad-spectrum antibiotics and are emerging as promising alternative antimicrobials. However, phage-mediated killing is often limited by bacterial resistance development. Here, we engineer phages for target-specific effector gene delivery and host-dependent production of colicin-like bacteriocins and cell wall hydrolases. Using urinary tract infection (UTI) as a model, we show how heterologous effector phage therapeutics (HEPTs) suppress resistance and improve uropathogen killing by dual phage- and effector-mediated targeting. Moreover, we designed HEPTs to control polymicrobial uropathogen communities through production of effectors with cross-genus activity. Using phage-based companion diagnostics, we identified potential HEPT responder patients and treated their urine ex vivo. Compared to wildtype phage, a colicin E7-producing HEPT demonstrated superior control of patient E. coli bacteriuria. Arming phages with heterologous effectors paves the way for successful UTI treatment and represents a versatile tool to enhance and adapt phage-based precision antimicrobials