Identification of new omeprazole metabolites in wastewaters and surface waters

Omeprazole is one of the world-wide most consumed pharmaceuticals for treatment of gastric diseases. As opposed to other frequently used pharmaceuticals, omeprazole is scarcely detected in urban wastewaters and environmental waters. This was corroborated in a previous research, where parent omeprazole was not detected while four transformation products (TPs), mainly resulting from hydrolysis, were found in effluent wastewaters and surface waters. However, the low abundance of omeprazole TPs in the water samples together with the fact that omeprazole suffers an extensive metabolism, with a wide range of excretion rates (between 0.01 and 30%), suggests that human urinary metabolites should be investigated in the water environment. In this work, the results obtained in excretion tests after administration of a 40 mg omeprazole dose in three healthy volunteers are reported. Analysis by liquid chromatography coupled to hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF MS) reported low concentrations of omeprazole in urine. Up to twenty-four omeprazole metabolites (OMs) were detected and tentatively elucidated. The most relevant OM was an omeprazole isomer, which obviously presented the same exact mass (m/z 346.1225), but also shared a major common fragment at m/z 198.0589. Subsequent analyses of surface water and effluent wastewater samples by both LC-QTOF MS and LC-MS/MS with triple quadrupole revealed that this metabolite (named as OM10) was the compound most frequently detected in water samples, followed by OM14a and OM14b. Up to our knowledge, OM10 had not been used before as urinary biomarker of omeprazole in waters. On the contrary, parent omeprazole was never detected in any of the water samples. After this research, it seems clear that monitoring the presence of omeprazole in the aquatic environment should be focused on the OMs suggested in this article instead of the parent compound

A Light Calibration System for the ProtoDUNE-DP Detector

A LED-based fiber calibration system for the ProtoDUNE-Dual Phase (DP) photon detection system (PDS) has been designed and validated. ProtoDUNE-DP is a 6x6x6 m3 liquid argon time-projection-chamber currently being installed at the Neutrino Platform at CERN. The PDS is based on 36 8-inch photomultiplier tubes (PMTs) and will allow triggering on cosmic rays. The system serves as prototype for the PDS of the final DUNE DP far detector in which the PDS also has the function to allow the 3D event reconstruction on non-beam physics. For this purpose an equalized PMT response is desirable to allow using the same threshold definition for all PMT groups, simplifying the determination of the trigger efficiency. The light calibration system described in this paper is developed to provide this and to monitor the PMT performance in-situ.Comment: 15 pages, 5 figure

Deep subcutaneous application of poly-L-lactic acid as a filler for facial lipoatrophy in HIV-infected patients

Introduction: Facial lipoatrophy is a crucial problem of HIV-infected patients undergoing highly active antiretroviral therapy (HAART). Poly-L-lactic acid (PLA), provided as New-Fill(R)/Sculptra(TM), is known as one possible treatment option. In 2004 PLA was approved by the FDA as Sculptra(TM) for the treatment of lipoatrophy of the face in HIV-infected patients. While the first trials demonstrated relevant efficacy, this was to some extent linked to unwanted effects. As the depth of injection was considered relevant in this context, the application modalities of the preparation were changed. The preparation was to be injected more deeply into subcutaneous tissue, after increased dilution. Material and Methods: To test this approach we performed a pilot study following the new recommendations in 14 patients. Results: While the efficacy turned out to be about the same, tolerability was markedly improved. The increase in facial dermal thickness was particularly obvious in those patients who had suffered from lipoatrophy for a comparatively small period of time. Conclusion: With the new recommendations to dilute PLA powder and to inject it into the deeper subcutaneous tissue nodule formation is a minor problem. However, good treatment results can only be achieved if lipoatrophy is not too intense; treatment intervals should be about 2 - 3 weeks. Copyright (C) 2005 S. Karger AG, Basel

A Study of Concurrency Bugs and Advanced Development Support for Actor-based Programs

The actor model is an attractive foundation for developing concurrent applications because actors are isolated concurrent entities that communicate through asynchronous messages and do not share state. Thereby, they avoid concurrency bugs such as data races, but are not immune to concurrency bugs in general. This study taxonomizes concurrency bugs in actor-based programs reported in literature. Furthermore, it analyzes the bugs to identify the patterns causing them as well as their observable behavior. Based on this taxonomy, we further analyze the literature and find that current approaches to static analysis and testing focus on communication deadlocks and message protocol violations. However, they do not provide solutions to identify livelocks and behavioral deadlocks. The insights obtained in this study can be used to improve debugging support for actor-based programs with new debugging techniques to identify the root cause of complex concurrency bugs.Comment: - Submitted for review - Removed section 6 "Research Roadmap for Debuggers", its content was summarized in the Future Work section - Added references for section 1, section 3, section 4.3 and section 5.1 - Updated citation

Nanosized Sodium-Doped Lanthanum Manganites: Role of the Synthetic Route on their Physical Properties

In this paper we present the results of the synthesis and characterisation of nanocrystalline La1-xNaxMnO3+delta samples. Two synthetic routes were employed: polyacrylamide-based sol-gel and propellant synthesis. Pure, single phase materials were obtained with grain size around 35 nm for the sol-gel samples and around 55 nm for the propellant ones, which moreover present a more broaden grain size distribution. For both series a superparamagnetic behaviour was evidenced by means of magnetisation and EPR measurements with peculiar features ascribable to the different grain sizes and morphology. Preliminary magnetoresistivity measurements show enhanced low-field (< 1 T) magnetoresistance values which suggest an interesting applicative use of these manganites.Comment: 31 Pages 10 Figures to appear in Chem. Mate

The effects of male social environment on sperm phenotype and genome integrity

Sperm function and quality are primary determinants of male reproductive performance and hence fitness. The presence of rival males has been shown to affect ejaculate and sperm traits in a wide range of taxa. However, male physiological conditions may not only affect sperm phenotypic traits but also their genetic and epigenetic signatures, affecting the fitness of the resulting offspring. We investigated the effects of male-male competition on sperm quality using TUNEL assays and geometric morphometrics in the zebrafish, Danio rerio. We found that the sperm produced by males exposed to high male-male competition had smaller heads but larger midpiece and flagellum than sperm produced by males under low competition. Head and flagella also appeared less sensitive to the osmotic stress induced by activation with water. In addition, more sperm showed signals of DNA damage in ejaculates of males under high competition. These findings suggest that the presence of a rival male may have positive effects on phenotypic traits but negative effects on DNA integrity. Overall, males facing the presence of rival males may produce faster swimming and more competitive sperm but this may come at a cost for the next generation. This article is protected by copyright. All rights reserved

Variation in developmental rates is not linked to environmental unpredictability in annual killifishes

Comparative evidence suggests that adaptive plasticity may evolve as a response to predictable environmental variation. However, less attention has been placed on unpredictable environmental variation, which is considered to affect evolutionary trajectories by increasing phenotypic variation (or bet hedging). Here, we examine the occurrence of bet hedging in egg developmental rates in seven species of annual killifish that originate from a gradient of variation in precipitation rates, under three treatment incubation temperatures (21, 23, and 25 degrees C). In the wild, these species survive regular and seasonal habitat desiccation, as dormant eggs buried in the soil. At the onset of the rainy season, embryos must be sufficiently developed in order to hatch and complete their life cycle. We found substantial differences among species in both the mean and variation of egg development rates, as well as species-specific plastic responses to incubation temperature. Yet, there was no clear relationship between variation in egg development time and variation in precipitation rate (environmental predictability). The exact cause of these differences therefore remains enigmatic, possibly depending on differences in other natural environmental conditions in addition to precipitation predictability. Hence, if species-specific variances are adaptive, the relationship between development and variation in precipitation is complex and does not diverge in accordance with simple linear relationships

The Cherenkov Telescope Array Large Size Telescope

The two arrays of the Very High Energy gamma-ray observatory Cherenkov Telescope Array (CTA) will include four Large Size Telescopes (LSTs) each with a 23 m diameter dish and 28 m focal distance. These telescopes will enable CTA to achieve a low-energy threshold of 20 GeV, which is critical for important studies in astrophysics, astroparticle physics and cosmology. This work presents the key specifications and performance of the current LST design in the light of the CTA scientific objectives.Comment: 4 pages, 5 figures, In Proceedings of the 33rd International Cosmic Ray Conference (ICRC2013), Rio de Janeiro (Brazil). All CTA contributions at arXiv:1307.223