Enteral Glutamine Administration in Critically Ill Nonseptic Patients Does Not Trigger Arginine Synthesis

Glutamine supplementation in specific groups of critically ill patients results in favourable clinical outcome. Enhancement of citrulline and arginine synthesis by glutamine could serve as a potential mechanism. However, while receiving optimal enteral nutrition, uptake and enteral metabolism of glutamine in critically ill patients remain unknown. Therefore we investigated the effect of a therapeutically relevant dose of L-glutamine on synthesis of L-citrulline and subsequent L-arginine in this group. Ten versus ten critically ill patients receiving full enteral nutrition, or isocaloric isonitrogenous enteral nutrition including 0.5 g/kg L-alanyl-L-glutamine, were studied using stable isotopes. A cross-over design using intravenous and enteral tracers enabled splanchnic extraction (SE) calculations. Endogenous rate of appearance and SE of glutamine citrulline and arginine was not different (SE controls versus alanyl-glutamine: glutamine 48 and 48%, citrulline 33 versus 45%, and arginine 45 versus 42%). Turnover from glutamine to citrulline and arginine was not higher in glutamine-administered patients. In critically ill nonseptic patients receiving adequate nutrition and a relevant dose of glutamine there was no extra citrulline or arginine synthesis and glutamine SE was not increased. This suggests that for arginine synthesis enhancement there is no need for an additional dose of glutamine when this population is adequately fed. This trial is registered with NTR228

Measurement of fraction unbound paclitaxel in human plasma

The clinical pharmacokinetic behavior of paclitaxel (Taxol) is distinctly nonlinear, with disproportional increases in systemic exposure with an increase in dose. We have recently shown that Cremophor EL, the formulation vehicle used for i.v. administration of paclitaxel, alters drug distribution as a result of micellar entrapment of paclitaxel, and we speculated that the free drug fraction (fu) is dependent on dose and time-varying concentrations of Cremophor EL in the central plasma compartment. To test this hypothesis, a reproducible equilibrium dialysis method has been developed for the measurement of paclitaxel fu in plasma. Equilibrium dialysis was performed at 37 degrees C in a humidified atmosphere of 5% CO(2) using 2.0-ml polypropylene test tubes. Experiments were carried out with 260-microliter aliquots of plasma containing a tracer amount of [G-(3)H]paclitaxel with high-specific activity against an equal volume of 0.01 M phosphate buffer (pH 7.4). Drug concentrations were measured by both reversed-phase HPLC and liquid scintillation counting. Using this method, fu has been measured in three patients receiving three consecutive 3-weekly courses of paclitaxel at dose levels of 135, 175, and 225 mg/m(2) and found to range between 0.036 and 0.079. The method was also used to define concentration-time profiles of unbound drug, estimated from the product of the total plasma concentration and fu

A solution approach for deriving alternative fuel station infrastructure requirements

When an alternative fuel is introduced, the infrastructure through which that fuel is made available to the market is often underdeveloped. Transportation service providers relying on such infrastructures are unlikely to adopt alternative fuel vehicles as it may impose long detours for refueling. In this paper, we design and apply a new solution approach to derive minimum infrastructure requirements, in terms of the number of alternative fuel stations. The effectiveness of our approach is demonstrated by applying it to the case of introducing liquefied natural gas (LNG) as a transportation fuel in The Netherlands. From this case, we learn that, depending on the driving range of the LNG trucks and the size of area on which those trucks operate, a minimum of 5-12 LNG fuel stations is necessary to render LNG trucks economically and environmentally beneficial

Unfolding-Based Process Discovery

This paper presents a novel technique for process discovery. In contrast to the current trend, which only considers an event log for discovering a process model, we assume two additional inputs: an independence relation on the set of logged activities, and a collection of negative traces. After deriving an intermediate net unfolding from them, we perform a controlled folding giving rise to a Petri net which contains both the input log and all independence-equivalent traces arising from it. Remarkably, the derived Petri net cannot execute any trace from the negative collection. The entire chain of transformations is fully automated. A tool has been developed and experimental results are provided that witness the significance of the contribution of this paper.Comment: This is the unabridged version of a paper with the same title appearead at the proceedings of ATVA 201

Learning through social spaces: migrant women and lifelong learning in post-colonial London

This article shows how migrant women engage in learning through social spaces. It argues that such spaces are little recognised, and that there are multiple ways in which migrant women construct and negotiate their informal learning through socialising with other women in different informal modes. Additionally, the article shows how learning is shaped by the socio-political, geographical and multicultural context of living in London, outlining ways in which gendered and racialised identities shape, construct and constrain participation in lifelong learning. The article shows that one way in which migrant women resist (post)colonial constructions of difference is by engaging in informal and non-formal lifelong learning, arguing that the benefits are (at least) two-fold. The women develop skills (including language skills) but also use their informal learning to develop what is referred to in this article as 'relational capital'. The article concludes that informal lifelong learning developed through social spaces can enhance a sense of belonging for migrant women

Heat transport by lattice and spin excitations in the spin chain compounds SrCuO_2 and Sr_2CuO_3

We present the results of measurements of the thermal conductivity of the quasi one-dimensional spin S=1/2 chain compound SrCuO_2 in the temperature range between 0.4 and 300 K along the directions parallel and perpendicular to the chains. An anomalously enhanced thermal conductivity is observed along the chains. The analysis of the present data and a comparison with analogous recent results for Sr_2CuO_3 and other similar materials demonstrates that this behavior is generic for cuprates with copper-oxygen chains and strong intrachain interactions. The observed anomalies are attributed to the one-dimensional energy transport by spin excitations (spinons), limited by the interaction between spin and lattice excitations. The energy transport along the spin chains has a non-diffusive character, in agreement with theoretical predictions for integrable models.Comment: 12 pages (RevTeX), 8 figure

Relativistically rotating dust

Dust configurations play an important role in astrophysics and are the simplest models for rotating bodies. The physical properties of the general--relativistic global solution for the rigidly rotating disk of dust, which has been found recently as the solution of a boundary value problem, are discussed.Comment: 18 pages, 11 figure

Diagnosing Clostridioides difficile infections with molecular diagnostics: multicenter evaluation of revogene C. difficile assay

Clostridioides difficile infections are a significant threat to our healthcare system, and rapid and accurate diagnostics are crucial to implement the necessary infection prevention and control measurements. Nucleic acid amplification tests are such reliable diagnostic tools for the detection of toxigenic Clostridioides difficile strains directly from stool specimens. In this multicenter evaluation, we determined the performance of the revogene C. difficile assay. The analysis was conducted on prospective stool specimens collected from six different sites in Europe. The performance of the revogene C. difficile assay was compared to the different routine diagnostic methods and, for a subset of the specimens, against toxigenic culture. In total, 2621 valid stool specimens were tested, and the revogene C. difficile assay displayed a sensitivity/specificity of 97.1% [93.3-99.0] and 98.9% [98.5-99.3] for identification of Clostridioides difficile infection. Discrepancy analysis using additional methods improved this performance to 98.8% [95.8-99.9] and 99.6% [99.2-99.8], respectively. In comparison to toxigenic culture, the revogene C. difficile assay displayed a sensitivity/specificity of 93.0% [86.1-97.1] and 99.5% [98.7-99.9], respectively. These results indicate that the revogene C. difficile assay is a robust and reliable aid in the diagnosis of Clostridioides difficile infections.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.This study was supported by grants from GenePOC, now part of Meridian Biosciences.published version, accepted versio