TY - JOUR A1 - Dupuis, Luc A1 - Dengler, Reinhard A1 - Heneka, Michael T. A1 - Meyer, Thomas A1 - Zierz, Stephan A1 - Kassubek, Jan A1 - Fischer, Wilhelm A1 - Steiner, Franziska A1 - Lindauer, Eva A1 - Otto, Markus A1 - Dreyhaupt, Jens A1 - Grehl, Torsten A1 - Hermann, Andreas A1 - Winkler, Andrea S. A1 - Bogdahn, Ulrich A1 - Benecke, Reiner A1 - Schrank, Bertold A1 - Wessig, Carsten A1 - Grosskreutz, Julian A1 - Ludolph, Albert C. T1 - A Randomized, Double Blind, Placebo-Controlled Trial of Pioglitazone in Combination with Riluzole in Amyotrophic Lateral Sclerosis JF - PLoS One N2 - Background: Pioglitazone, an oral anti-diabetic that stimulates the PPAR-gamma transcription factor, increased survival of mice with amyotrophic lateral sclerosis (ALS). Methods/Principal Findings: We performed a phase II, double blind, multicentre, placebo controlled trial of pioglitazone in ALS patients under riluzole. 219 patients were randomly assigned to receive 45 mg/day of pioglitazone or placebo (one: one allocation ratio). The primary endpoint was survival. Secondary endpoints included incidence of non-invasive ventilation and tracheotomy, and slopes of ALS-FRS, slow vital capacity, and quality of life as assessed using EUROQoL EQ-5D. The study was conducted under a two-stage group sequential test, allowing to stop for futility or superiority after interim analysis. Shortly after interim analysis, 30 patients under pioglitazone and 24 patients under placebo had died. The trial was stopped for futility; the hazard ratio for primary endpoint was 1.21 (95% CI: 0.71-2.07, p = 0.48). Secondary endpoints were not modified by pioglitazone treatment. Pioglitazone was well tolerated. Conclusion/Significance: Pioglitazone has no beneficial effects on the survival of ALS patients as add-on therapy to riluzole. KW - ALS KW - transgenic mouse model KW - central nervous system KW - nonalcoholic steatohepatitis KW - PPAR-gamme KW - hexanucleotide repeat KW - disease progression KW - delays progression KW - SOD1 mutations KW - monocycline Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130255 VL - 7 IS - 6 ER - TY - THES A1 - Meyer, Markus T1 - Observations of a systematically selected sample of high frequency peaked BL Lac objects with the MAGIC telescope T1 - Beobachtungen eines systematisch ausgewählten Samples von "high frequency peaked" BL Lac Objekten mit dem MAGIC Teleskop N2 - At the beginning of regular observations with the MAGIC telescope in December 2004, all but one extragalactic sources detected at very high energy (VHE) gamma-rays belonged to the class of high frequency peaked BL Lac (HBL) objects. This motivated a systematic scan of candidate sources to increase the number of known sources and to study systematically their spectral properties. As candidate sources for VHE emission, X-ray bright HBLs were selected from a compilation of active galactic nuclei. The MAGIC observations took place from December 2004 to March 2006. The declination of the objects was restricted to values between -1.2° and +58.8° corresponding to a maximum zenith distance lower than 30° at culmination. Since gamma-rays are absorbed by photo-pair production in low energy background radiation fields, the redshift of the investigated objects was limitetd to z < 0.3. Under the assumption that HBLs generally emit the same energy flux at 1keV as at 200GeV, only the brightest X-ray sources were observed, leading to a cut in the X-ray flux of F(1keV) > 2µJy}. Of the fourteen sources observed, four have been detected: 1ES 1218+304 (for the first time at very high energies), 1ES 2344+514 (strong detection in a state of low activity), Mrk 421 and Mrk 501. A hint of a signal on a 3-sigma-level from the direction of 1ES 1011+496 has been observed. In the meantime the object has been confirmed as a source of VHE gamma-rays by a second MAGIC observation campaign triggered by an optical outburst. For ten sources, upper limits on their integral fluxes above 200GeV have been calculated on a 99% confidence level. To cross calibrate the different data samples, collected during 14 months, bright muon ring images have been used, recorded as background events by the MAGIC telescope. Based on the development by Meyer (2003), the method has been improved and implemented into the automatic data analysis as a continuous monitor of the calibration and the point spread function of the optical system. While the ring images are generated by muons with small impact parameters, it could be shown that the image parameter distributions for muons with large impact parameters and gamma showers completely overlap, revealing these muons as the dominant background for gamma-ray observations below energies of 150GeV. The sample of HBLs (including all HBLs detected at VHE so far) has been investigated for correlations between broad-band spectral indices as determined from simultaneous optical, archival X-ray and radio luminosities, finding that the VHE emitting HBLs do not differ from the non-detected ones. In general the absorption corrected HBL gamma-ray luminosities at 200GeV are not higher than their X-ray luminosities at 1keV. Based on a complete X-ray BL Lac sample, the Hamburg/ROSAT X-ray BL Lac sample, the number of expected VHE sources has been estimated for the performed scan, finding a consistent number under the assumption of a 37% completeness of the investigated sample and a 1keV-to-200GeV luminosity ratio of 1.4. An upper limit on the omnidirectional flux at 200GeV has been calculated by interpolating the sum over the observed fluxes and upper limits. Within the uncertainties, the result is in agreement with the expectations derived from the X-ray luminosity function of BL Lacs. For 1ES 1218+304 and 1ES 2344+514 the lightcurves have been derived, showing evidence for flux variability on a time scale of 17 days and 24h, respectively. In the case of 1ES 1218+304 variability has been reported for the first time at VHEs. For both sources the energy spectra have been reconstructed and discussed in the context of their broad band spectral energy distribution (SED), using a single zone synchrotron self Compton model. The SEDs are well fitted by the simulation even though the very high peak frequencies at gamma-rays push the model to its limits. The parameters derived from the simulation are in good agreement with the parameters found for similar HBLs. N2 - Zu Beginn der regulären Beobachtungen des MAGIC-Teleskops im Dezember 2004 gehörten alle extragalaktischen Quellen, bis auf eine, von denen sehr hochenergetische (VHE von engl. very high energy) Gammastrahlung detektiert wurde, zur Klasse der sogenannten "high frequency peaked BL Lac"-Objekte (HBL). Dies motivierte eine systematische Durchmusterung von Quellkandidaten mit dem Ziel die Anzahl der bekannten Quellen zu erhöhen und ihre spektralen Eigenschaften systematisch zu untersuchen. Als Quellkandidaten für VHE-Emission wurden röntgen-helle HBLs aus einer Kompilation von aktiven galaktischen Kernen ausgewählt. Die MAGIC-Beobachtungen fanden von Dezember 2004 bis März 2006 statt. Die Deklination der Objekte war begrenzt auf Werte zwischen -1.2° und +58.8°, entsprechend einer Zenitdistanz von weniger als 30° an der Kulmination. Da Gammastrahlung durch Photo-Paar-Produktion in niederenergetischen Hintergrundstrahlungsfeldern absorbiert wird, wurde die Rotverschiebung der untersuchten Objekte auf z < 0.3 begrenzt. Unter der Annahme, dass HBLs generell den selben Energieflu{ss} bei 1keV wie bei 200GeV emittieren, wurden nur die hellsten Röntgenquellen beobachtet, was zu einem Schnitt im Röntgenfluß von F(1keV) > 2µJy führte. Von den vierzehn beobachteten Objekten konnten vier detektiert werden: 1ES 1218+304 (zum ersten Mal im VHE-Bereich), 1ES 2344+514 (klare Detektion in einem Zustand niedriger Aktivität), Mrk 421 und Mrk 501. Ein Hinweis auf ein Signal auf einem 3-sigma-Level wurde aus der Richtung von 1ES 1011+496 beobachtet. Inzwischen ist das Objekt als eine Quelle hochenergetischer Gammastrahlung in einer zweiten MAGIC-Beobachtungskampagne, die durch einen hohen optischen Flusszustand ausgelöst wurde, bestätigt worden. Für die übrigen zehn Quellen wurden Obergrenzen an den integralen Fluss oberhalb von 200GeV mit einer statistischen Sicherheit von 99% berechnet. Um eine Kreuzkalibrierung verschiedener Datensätze, genommen innerhalb von 14 Monaten, durchzuführen, wurden helle Bilder von Myonenringen verwendet, die als Hintergrundereignisse vom MAGIC Teleskop aufgenommen werden. Basierend auf der Entwicklung von Meyer (2003) wurde die Methode verbessert und als ein kontinuierlicher Monitor der Kalibrierung sowie der Punktbildfunktion des optischen Systems in die automatische Datenanalyse implementiert. Während die Ringbilder von Myonen mit kleinen Stoßparametern erzeugt werden, konnte gezeigt werden, dass die Verteilungen der Bildparameter von Myonen mit großen Stoßparametern und der von Gammaschauern sich vollständig überlappen, was diese Myonen zum dominierenden Hintergrund für die Beobachtung von Gammastrahlung unterhalb einer Enegie von 150GeV macht. Das HBL-Sample (inklusive aller HBLs, die bisher bei sehr hohen Energien detektiert wurden) wurde nach Korrelationen zwischen den Breitband-Spektralindices untersucht, die durch simultane optische sowie durch Röntgen- und Radio-Leuchtkräfte aus früheren Beobachtungen bestimmt wurden, mit dem Ergebnis, dass die VHE-emittierenden HBLs sich nicht von den nicht-detektierten unterscheiden. Generell sind die absorptionskorrigierten Gammaleuchtkräfte der HBLs bei 200GeV nicht höher als ihre Röntgenleuchtkräfte bei 1keV. Basierend auf einem vollständigen Röntgen-BL Lac-Sample, dem Hamburg-ROSAT-Röntgen-BL Lac-Sample, wurde die Anzahl der zu erwartenden VHE-Quellen für die durchgeführte Durchmusterung abgeschätzt, wobei eine konsistente Anzahl erreicht wird, unter der Annahme einer Vollständigkeit des untersuchten Samples von 37% sowie ein 1keV-zu-200GeV Leuchtkraftverhältnis von 1,4. Eine Obergrenze an den gesammten Fluss pro Raumwinkel bei 200GeV wurde durch eine Interpolation der Summe der beobachteten Flüsse und Fluss-Obergrenzen berechnet. Innerhalb der Ungenauigkeiten ist das Ergebnis in Übereinstimmung mit den Erwartungen die aus der Röntgen-Leuchtkraftfunktion der BL Lacs abgeleitet wurde. Für 1ES 1218+304 und 1ES 2344+514 wurden die Lichtkurven bestimmt, welche Anzeichen von Flussvariabilität auf einer Zeitskala von 17 Tagen beziehungsweise 24 Stunden aufweisen. Im Falle von 1ES 1218+304 wurde zum ersten Mal zeitliche Variabilität bei sehr hohen Energien gesehen. Für beide Quellen wurden die Energiespektren rekonstruiert und im Kontext ihrer spektralen Energieverteilung (SED) diskutiert, wobei ein ein-Zonen-Synchrotron-selbst-Compton-Modell verwendet wurde. Die SEDs wurden von der Simulation gut beschrieben, auch wenn die sehr hohen Energien der Maxima im Gammabereich das Modell an seine Grenzen bringen. Die von der Simulation abgeleiteten Parameter stimmen gut mit den Parametern, die für ähnliche HBLs gefunden wurden überein. KW - Aktiver galaktischer Kern KW - Gammastrahlung KW - active galactic nuclei KW - gamma radiation KW - cherenkov telescope Y1 - 2008 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-28115 ER - TY - JOUR A1 - Surat, Güzin A1 - Meyer-Sautter, Pascal A1 - Rüsch, Jan A1 - Braun-Feldweg, Johannes A1 - Markus, Christian Karl A1 - Germer, Christoph-Thomas A1 - Lock, Johan Friso T1 - Cefazolin might be adequate for perioperative antibiotic prophylaxis in intra-abdominal infections without sepsis: a quality improvement study JF - Antibiotics N2 - Background: The adequate choice of perioperative antibiotic prophylaxis (PAP) could influence the risk of surgical site infections (SSIs) in general surgery. A new local PAP guideline was implemented in May 2017 and set the first-generation cefazolin (CFZ) instead the second-generation cefuroxime (CXM) as the new standard prophylactic antibiotic. The aim of this study was to compare the risk of SSIs after this implementation in intra-abdominal infections (IAIs) without sepsis. Methods: We performed a single center-quality improvement study at a 1500 bed sized university hospital in Germany analyzing patients after emergency surgery during 2016 to 2019 (n = 985), of which patients receiving CXM or CFZ were selected (n = 587). Propensity score matching was performed to ensure a comparable risk of SSIs in both groups. None-inferiority margin for SSIs was defined as 8% vs. 4%. Results: Two matched cohorts with respectively 196 patients were compared. The rate of SSIs was higher in the CFZ group (7.1% vs. 3.6%, p = 0.117) below the non-inferiority margin. The rate of other postoperative infections was significantly higher in the CFZ group (2.0% vs. 8.7%, p = 0.004). No other differences including postoperative morbidity, mortality or length-of-stay were observed. Conclusion: Perioperative antibiotic prophylaxis might be safely maintained by CFZ even in the treatment of intra-abdominal infections. KW - antimicrobial stewardship KW - antibiotic prescribing quality KW - low-risk intra-abdominal infections KW - perioperative antibiotic prophylaxis Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270816 SN - 2079-6382 VL - 11 IS - 4 ER - TY - JOUR A1 - Ziegler, Alice A1 - Meyer, Hanna A1 - Otte, Insa A1 - Peters, Marcell K. A1 - Appelhans, Tim A1 - Behler, Christina A1 - Böhning-Gaese, Katrin A1 - Classen, Alice A1 - Detsch, Florian A1 - Deckert, Jürgen A1 - Eardley, Connal D. A1 - Ferger, Stefan W. A1 - Fischer, Markus A1 - Gebert, Friederike A1 - Haas, Michael A1 - Helbig-Bonitz, Maria A1 - Hemp, Andreas A1 - Hemp, Claudia A1 - Kakengi, Victor A1 - Mayr, Antonia V. A1 - Ngereza, Christine A1 - Reudenbach, Christoph A1 - Röder, Juliane A1 - Rutten, Gemma A1 - Schellenberger Costa, David A1 - Schleuning, Matthias A1 - Ssymank, Axel A1 - Steffan-Dewenter, Ingolf A1 - Tardanico, Joseph A1 - Tschapka, Marco A1 - Vollstädt, Maximilian G. R. A1 - Wöllauer, Stephan A1 - Zhang, Jie A1 - Brandl, Roland A1 - Nauss, Thomas T1 - Potential of airborne LiDAR derived vegetation structure for the prediction of animal species richness at Mount Kilimanjaro JF - Remote Sensing N2 - The monitoring of species and functional diversity is of increasing relevance for the development of strategies for the conservation and management of biodiversity. Therefore, reliable estimates of the performance of monitoring techniques across taxa become important. Using a unique dataset, this study investigates the potential of airborne LiDAR-derived variables characterizing vegetation structure as predictors for animal species richness at the southern slopes of Mount Kilimanjaro. To disentangle the structural LiDAR information from co-factors related to elevational vegetation zones, LiDAR-based models were compared to the predictive power of elevation models. 17 taxa and 4 feeding guilds were modeled and the standardized study design allowed for a comparison across the assemblages. Results show that most taxa (14) and feeding guilds (3) can be predicted best by elevation with normalized RMSE values but only for three of those taxa and two of those feeding guilds the difference to other models is significant. Generally, modeling performances between different models vary only slightly for each assemblage. For the remaining, structural information at most showed little additional contribution to the performance. In summary, LiDAR observations can be used for animal species prediction. However, the effort and cost of aerial surveys are not always in proportion with the prediction quality, especially when the species distribution follows zonal patterns, and elevation information yields similar results. KW - biodiversity KW - species richness KW - LiDAR KW - elevation KW - partial least square regression KW - arthropods KW - birds KW - bats KW - predictive modeling Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262251 SN - 2072-4292 VL - 14 IS - 3 ER - TY - JOUR A1 - Krüger, Timothy A1 - Maus, Katharina A1 - Kreß, Verena A1 - Meyer-Natus, Elisabeth A1 - Engstler, Markus T1 - Single-cell motile behaviour of Trypanosoma brucei in thin-layered fluid collectives JF - The European Physical Journal E N2 - We describe a system for the analysis of an important unicellular eukaryotic flagellate in a confining and crowded environment. The parasite Trypanosoma brucei is arguably one of the most versatile microswimmers known. It has unique properties as a single microswimmer and shows remarkable adaptations (not only in motility, but prominently so), to its environment during a complex developmental cycle involving two different hosts. Specific life cycle stages show fascinating collective behaviour, as millions of cells can be forced to move together in extreme confinement. Our goal is to examine such motile behaviour directly in the context of the relevant environments. Therefore, for the first time, we analyse the motility behaviour of trypanosomes directly in a widely used assay, which aims to evaluate the parasites behaviour in collectives, in response to as yet unknown parameters. In a step towards understanding whether, or what type of, swarming behaviour of trypanosomes exists, we customised the assay for quantitative tracking analysis of motile behaviour on the single-cell level. We show that the migration speed of cell groups does not directly depend on single-cell velocity and that the system remains to be simplified further, before hypotheses about collective motility can be advanced. KW - Trypanosoma brucei KW - motile behaviour KW - fluid collectives Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-273022 SN - 1292-895X VL - 44 IS - 3 ER - TY - JOUR A1 - Kramer, Susanne A1 - Meyer-Natus, Elisabeth A1 - Stigloher, Christian A1 - Thoma, Hanna A1 - Schnaufer, Achim A1 - Engstler, Markus T1 - Parallel monitoring of RNA abundance, localization and compactness with correlative single molecule FISH on LR White embedded samples JF - Nucleic Acids Research N2 - Single mRNA molecules are frequently detected by single molecule fluorescence in situ hybridization (smFISH) using branched DNA technology. While providing strong and background-reduced signals, the method is inefficient in detecting mRNAs within dense structures, in monitoring mRNA compactness and in quantifying abundant mRNAs. To overcome these limitations, we have hybridized slices of high pressure frozen, freeze-substituted and LR White embedded cells (LR White smFISH). mRNA detection is physically restricted to the surface of the resin. This enables single molecule detection of RNAs with accuracy comparable to RNA sequencing, irrespective of their abundance, while at the same time providing spatial information on RNA localization that can be complemented with immunofluorescence and electron microscopy, as well as array tomography. Moreover, LR White embedding restricts the number of available probe pair recognition sites for each mRNA to a small subset. As a consequence, differences in signal intensities between RNA populations reflect differences in RNA structures, and we show that the method can be employed to determine mRNA compactness. We apply the method to answer some outstanding questions related to trans-splicing, RNA granules and mitochondrial RNA editing in single-cellular trypanosomes and we show an example of differential gene expression in the metazoan Caenorhabditis elegans. KW - mRNA Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230647 VL - 49 IS - 3 ER -