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Lorenz, Manuel ; Agakishiev, Geydar ; Behnke, Claudia ; Belver, Daniel ; Belyaev, Alexei V. ; Berger-Chen, Jia-Chii ; Blanco, Alberto ; Blume, Christoph ; Böhmer, Michael ; Cabanelas Eiras, Pablo ; Chernenko, Sergey P. ; Dritsa, Christina ; Dybczak, Adrian ; Epple, Eliane ; Fabbietti, Laura ; Fateev, Oleg ; Fonte, Paulo ; Friese, Jürgen ; Fröhlich, Ingo ; Galatyuk, Tetyana ; Garzón, Juan A. ; Gill, Katharina ; Golubeva, Marina ; González-Díaz, Diégo ; Guber, Fedor ; Gumberidze, Malgorzata ; Harabasz, Szymon ; Hennino, Thierry ; Höhne, Claudia ; Holzmann, Romain ; Huck, Patrick ; Ierusalimov, Alexander P. ; Ivashkin, Alexander ; Jurkovič, Martin ; Kämpfer, Burkhard ; Karavicheva, Tatiana L. ; Koenig, Ilse ; Koenig, Wolfgang ; Kolb, Burkhard W. ; Korcyl, Grzegorz ; Kornakov, Georgy ; Kotte, Roland ; Krása, Antonin ; Krebs, Erik ; Krizek, Filip ; Kuc, Hubert ; Kugler, Andrej ; Kurepin, Alexander ; Kurilkin, Aleksey K. ; Kurilkin, Pavel ; Ladygin, Vladimir P. ; Lalik, Rafał Tomasz ; Lang, Simon Martin ; Lapidus, Kirill ; Lebedev, Alexei ; Lopes, Luis Alberto Vieira ; Maier, Ludwig W. ; Mangiarotti, Alessio ; Markert, Jochen ; Metag, Volker ; Michel, Jan ; Müntz, Christian ; Münzer, Robert Helmut ; Naumann, Lothar ; Palka, Marek ; Parpottas, Yannis ; Pechenov, Vladimir ; Pechenova, Olga ; Pietraszko, Jerzy ; Przygoda, Witold ; Ramstein, Béatrice ; Rehnisch, Laura ; Reshetin, Andrey ; Rustamov, Anar ; Sadovsky, Alexander ; Salabura, Piotr ; Scheib, Timo ; Schuldes, Heidi ; Siebenson, Johannes Stephan ; Sobolev, Yuri G. ; Spataro, Stefano ; Ströbele, Herbert ; Stroth, Joachim ; Strzempek, Paweł ; Sturm, Christian Thomas ; Svoboda, Ondřej ; Tarantola Peloni, Attilio ; Teilab, Khaled ; Tlustý, Pavel ; Traxler, Michael ; Tsertos, Haralabos ; Vasiliev, Taras A. ; Wagner, Vladimir ; Weber, Michael ; Wendisch, Christian ; Wüstenfeld, Jörn ; Yurevich, Sergey ; Zanevsky, Yuri V.
The High Acceptance DiElectron Spectrometer HADES [1] is installed at the Helmholtzzentrum für Schwerionenforschung (GSI) accelerator facility in Darmstadt. It investigates dielectron emission and strangeness production in the 1-3 AGeV regime. A recent experiment series focusses on medium-modifications of light vector mesons in cold nuclear matter. In two runs, p+p and p+Nb reactions were investigated at 3.5 GeV beam energy; about 9·109 events have been registered. In contrast to other experiments the high acceptance of the HADES allows for a detailed analysis of electron pairs with low momenta relative to nuclear matter, where modifications of the spectral functions of vector mesons are predicted to be most prominent. Comparing these low momentum electron pairs to the reference measurement in the elementary p+p reaction, we find in fact a strong modification of the spectral distribution in the whole vector meson region.
Kurilkin, Pavel ; Agakishiev, Geydar ; Behnke, Claudia ; Belver, Daniel ; Belyaev, Alexei V. ; Berger-Chen, Jia-Chii ; Blanco, Alberto ; Blume, Christoph ; Böhmer, Michael ; Cabanelas Eiras, Pablo ; Chernenko, Sergey P. ; Dritsa, Christina ; Dybczak, Adrian ; Epple, Eliane ; Fabbietti, Laura ; Fateev, Oleg ; Fonte, Paulo J. R. ; Friese, Jürgen ; Fröhlich, Ingo ; Galatyuk, Tetyana ; Garzón, Juan A. ; Gill, Katharina ; Golubeva, Marina ; González-Díaz, Diégo ; Guber, Fedor ; Gumberidze, Malgorzata ; Harabasz, Szymon ; Hennino, Thierry ; Holzmann, Romain ; Huck, Patrick ; Höhne, Claudia ; Ierusalimov, Alexander P. ; Ivashkin, Alexander ; Jurkovič, Martin ; Kämpfer, Burkhard ; Karavicheva, Tatiana L. ; Koenig, Ilse ; Koenig, Wolfgang ; Kolb, Burkhard W. ; Korcyl, Grzegorz ; Kornakov, Georgy ; Kotte, Roland ; Krása, Antonin ; Krebs, Erik ; Krizek, Filip ; Kuc, Hubert ; Kugler, Andrej ; Kurepin, Alexander ; Kurilkin, Aleksey K. ; Ladygin, Vladimir P. ; Lalik, Rafał Tomasz ; Lang, Simon Martin ; Lapidus, Kirill ; Lebedev, Alexei ; Lopes, Luis Alberto Vieira ; Lorenz, Manuel ; Maier, Ludwig W. ; Mangiarotti, Alessio ; Markert, Jochen ; Metag, Volker ; Michel, Jan ; Müntz, Christian ; Münzer, Robert Helmut ; Naumann, Lothar ; Palka, Marek ; Parpottas, Yannis ; Pechenov, Vladimir ; Pechenova, Olga ; Pietraszko, Jerzy ; Przygoda, Witold ; Ramstein, Béatrice ; Rehnisch, Laura ; Reshetin, Andrey ; Rustamov, Anar ; Sadovsky, Alexander ; Salabura, Piotr ; Scheib, Timo ; Schuldes, Heidi ; Siebenson, Johannes Stephan ; Sobolev, Yuri G. ; Spataro, Stefano ; Ströbele, Herbert ; Stroth, Joachim ; Strzempek, Paweł ; Sturm, Christian Thomas ; Svoboda, Ondřej ; Tarantola Peloni, Attilio ; Teilab, Khaled ; Tlustý, Pavel ; Traxler, Michael ; Tsertos, Haralabos ; Vasiliev, Taras A. ; Wagner, Vladimir ; Weber, Michael ; Wendisch, Christian ; Wüstenfeld, Jörn ; Yurevich, Sergey ; Zanevsky, Yuri V.
New results on the differential cross section in deuteron-proton elastic scattering are obtained at the deuteron kinetic energy of 2.5 GeV with the HADES spectrometer. The angular range of 69° – 125° in the center of mass system is covered. The obtained results are compared with the relativistic multiple scattering model calculation using the CD-Bonn deuteron wave function. The data at fixed scattering angles in the c.m. are in qualitative agreement with the constituent counting rules prediction.
Abou Yassine, Rayane ; Adamczewski-Musch, Jörn ; Becker, Marten ; Bergmann, Philip ; Blanco, Alberto ; Blume, Christoph ; Chlad, Lukas ; Chudoba, Petr ; Ciepał, Izabela ; Cordts, Malte ; Dreyer, Jörn ; Esmail, Waleed Ahmed ; Firlej, Miroslaw ; Fiutowski, Tomasz ; Floersheimer, Henrik ; Fonte, Paulo ; Friese, Jürgen ; Fröhlich, Ingo ; Förtsch, Jörg ; Galatyuk, Tetyana ; Gniazdowski, Tomasz ; Greifenhagen, Robert ; Grunwald, Mateusz ; Grzonka, Dieter ; Gumberidze, Malgorzata ; Harabasz, Szymon ; Heinz, Thorsten ; Höhne, Claudia ; Hojeij, Fatima ; Holzmann, Romain ; Huck, Holger ; Idzik, Marek ; Kämpfer, Burkhard ; Kampert, Karl-Heinz ; Kardan, Behruz ; Kedych, Vadym ; Koenig, Ilse ; Koenig, Wolfgang ; Kohls, Marvin ; Kołaś, Jędrzej ; Korcyl, Grzegorz ; Kornakov, Georgy ; Kornas, Frédéric Julian ; Kotte, Roland ; Krueger, Wilhelm ; Kugler, Andrej ; Kulessa, Pawel ; Lalik, Rafał Tomasz ; Lebedev, Semen ; Linev, Sergey ; Lopes, Luis Alberto Vieira ; Lorenz, Manuel ; Malige, Akshay ; Markert, Jochen ; Matulewicz, Tomasz ; Messchendorp, Johannes Gerhardus ; Metag, Volker ; Michel, Jan ; Molenda, Aleksandra ; Moron, Jakub ; Müntz, Christian ; Nabroth, Marvin ; Naumann, Lothar ; Orliński, Jan ; Otto, Jan-Hendrik ; Parpottas, Yannis ; Parschau, Mirco ; Pauly, Christian ; Pechenov, Vladimir ; Pechenova, Olga ; Perez Andrade, Gabriela ; Pfeifer, Dennis ; Piasecki, Krzysztof ; Pietraszko, Jerzy ; Povar, Tetiana ; Prozorov, Alexandr ; Przygoda, Witold ; Pysz, Krzysztof ; Ramstein, Béatrice ; Rathod, Narendra ; Ritman, James Lambrecht ; Rost, Adrian ; Rustamov, Anar ; Salabura, Piotr ; Saraiva, Joao ; Schadmand, Susan ; Schild, Niklas ; Schwab, Erwin ; Seck, Florian ; Selyuzhenkov, Ilya ; Singh, Udai ; Skorpil, Leon ; Smyrski, Jerzy ; Sobiella, Manfred ; Spataro, Stefano ; Spies, Simon ; Stefaniak, Maria ; Ströbele, Herbert ; Stroth, Joachim ; Sumara, Konrad ; Svoboda, Ondřej ; Swientek, Krzysztof ; Szala, Melanie ; Tlusty, Pavel ; Traxler, Michael ; Tsertos, Haralabos ; Wagner, Vladimir ; Wasiluk, Mateusz ; Weber, Adrian Amatus ; Wendisch, Christian ; Wintz, Peter ; Zbroszczyk, Hanna Paulina ; Zherebtsova, Elizaveta S. ; Zielinski, Marcin ; Zumbruch, Peter W.
In March 2019 the HADES experiment recorded 14 billion Ag+Ag collisions at √sNN = 2.55 GeV as a part of the FAIR phase-0 physics program. In this contribution, we present and investigate our capabilities to reconstruct and analyze weakly decaying strange hadrons and hypernuclei emerging from these collisions. The focus is put on measuring the mean lifetimes of these particles.
The equity trading landscape all over the world has changed dramatically in recent years. We have witnessed the advent of new trading venues and significant changes in the market shares of existing ones. We use an extensive panel dataset from the European equity markets to analyze the market shares of five categories of lit and dark trading mechanisms. Market design features, such as minimum tick size, immediacy and anonymity; market conditions, such as liquidity and volatility; and the informational environment have distinct implications for order routing decisions and trading venues' resulting market shares. Furthermore, these implications differ distinctly for small and large trades, probably because traders jointly optimize their trade size and venue choice. Our results both confirm and go beyond current theoretical predictions on trading in fragmented markets.
Advances in technology and several regulatory initiatives have led to the emergence of a competitive but fragmented equity trading landscape in the US and Europe. While these changes have brought about several benefits like reduced transaction costs, regulators and market participants have also raised concerns about the potential adverse effects associated with increased execution complexity and the impact on market quality of new types of venues like dark pools. In this article we review the theoretical and empirical literature examining the economic arguments and motivations underlying market fragmentation, as well as the resulting implications for investors' welfare. We start with the literature that views exchanges as natural monopolies due to presence of network externalities, and then examine studies which challenge this view by focusing on trader heterogeneity and other aspects of the microstructure of equity markets.
Langheinrich, Melanie ; Wirtz, Stefan ; Kneis, Barbara ; Gittler, Matthias M. ; Tyc, Olaf ; Schierwagen, Robert ; Brunner, Maximilian ; Krautz, Christian ; Weber, Georg F. ; Pilarsky, Christian ; Trebicka, Jonel ; Agaimy, Abbas ; Grützmann, Robert ; Kersting, Stephan
Postoperative complications after pancreatic surgery are still a significant problem in clinical practice. The aim of this study was to characterize and compare the microbiomes of different body compartments (bile duct, duodenal mucosa, pancreatic tumor lesion, postoperative drainage fluid, and stool samples; preoperative and postoperative) in patients undergoing pancreatic surgery for suspected pancreatic cancer, and their association with relevant clinical factors (stent placement, pancreatic fistula, and gland texture). For this, solid (duodenal mucosa, pancreatic tumor tissue, stool) and liquid (bile, drainage fluid) biopsy samples of 10 patients were analyzed using 16s rRNA gene next-generation sequencing. Our analysis revealed: (i) a distinct microbiome in the different compartments, (ii) markedly higher abundance of Enterococcus in patients undergoing preoperative stent placement in the common bile duct, (iii) significant differences in the beta diversity between patients who developed a postoperative pancreatic fistula (POPF B/C), (iv) patients with POPF B/C were more likely to have bacteria belonging to the genus Enterococcus, and (v) differences in microbiome composition with regard to the pancreatic gland texture. The structure of the microbiome is distinctive in different compartments, and can be associated with the development of a postoperative pancreatic fistula.
Raimann, Florian ; Tepperis, Daniel Martin ; Meininger, Dirk ; Zacharowski, Kai ; Schalk, Richard ; Byhahn, Christian ; Weber, Christian Friedrich ; Mutlak, Haitham
Background. Tracheal intubation still represents the "gold standard" in securing the airway of unconscious patients in the prehospital setting. Especially in cases of restricted access to the patient, video laryngoscopy became more and more relevant.
Objectives. The aim of the study was to evaluate the performance and intubation success of four different video laryngoscopes, one optical laryngoscope, and a Macintosh blade while intubating from two different positions in a mannequin trial with difficult access to the patient.
Methods. A mannequin with a cervical collar was placed on the driver’s seat. Intubation was performed with six different laryngoscopes either through the driver’s window or from the backseat. Success, C/L score, time to best view (TTBV), time to intubation (TTI), and number of attempts were measured. All participants were asked to rate their favored device.
Results. Forty-two physicians participated. 100% of all intubations performed from the backseat were successful. Intubation success through the driver’s window was less successful. Only with the Airtraq® optical laryngoscope, 100% success was achieved. Best visualization (window C/L 2a; backseat C/L 2a) and shortest TTBV (window 4.7 s; backseat 4.1 s) were obtained when using the D-Blade video laryngoscope, but this was not associated with a higher success through the driver’s window. Fastest TTI was achieved through the window (14.2 s) when using the C-MAC video laryngoscope and from the backseat (7.3 s) when using a Macintosh blade.
Conclusions. Video laryngoscopy revealed better results in visualization but was not associated with a higher success. Success depended on the approach and familiarity with the device. We believe that video laryngoscopy is suitable for securing airways in trapped accident victims. The decision for an optimal device is complicated and should be based upon experience and regular training with the device.
Scherer, Christian ; Weber, Annkatrin ; Stock, Friederike ; Vurusic, Sebastijan ; Egerci, Harun ; Kochleus, Christian ; Arendt, Niklas ; Földi, Corinna ; Dierkes, Georg ; Wagner, Martin ; Brennholt, Nicole ; Reifferscheid, Georg
Aquatic ecosystems are globally contaminated with microplastics (MP). However, comparative data on MP levels in freshwater systems is still scarce. Therefore, the aim of this study is to quantify MP abundance in water and sediment of the German river Elbe using visual, spectroscopic (Fourier-transform infrared spectroscopy) and thermo analytical (pyrolysis gas chromatography mass spectrometry) methods. Samples from eleven German sites along the German part of the Elbe were collected, both in the water and sediment phase, in order to better understand MP sinks and transport mechanisms. MP concentrations differed between the water and sediment phase. Sediment concentrations (mean: 3,350,000 particles m−3, 125–5000 μm MP) were in average 600,000-fold higher than water concentrations (mean: 5.57 particles m−3, 150–5000 μm MP). The abundance varied between the sampling sites: In sediments, the abundance decreased in the course of the river while in water samples no such clear trend was observed. This may be explained by a barrage retaining sediments and limiting tidal influence in the upstream parts of the river. Particle shape differed site-specifically with one site having exceptionally high quantities of spheres, most probably due to industrial emissions of PS-DVB resin beads. Suspended MP consisted predominantly of polyethylene and polypropylene whereas sediments contained a higher diversity of polymer types. Determined MP concentrations correspond well to previous results from other European rivers. In a global context, MP levels in the Elbe relate to the lower (water) to middle section (sediment) of the global range of MP concentrations determined for rivers worldwide. This highlights that elevated MP levels are not only found in single countries or continents, but that MP pollution is an issue of global concern.
Gaubatz, Jennifer ; Prillwitz, Conrad ; Ernst, Leon ; David, Bastian ; Hoppe, Christian ; Hattingen, Elke ; Weber, Bernd ; Vatter, Hartmut ; Surges, Rainer ; Elger, Christian Erich ; Rüber, Theodor
Cerebral lesions may cause degeneration and neuroplastic reorganization in both the ipsi- and the contralesional hemisphere, presumably creating an imbalance of primarily inhibitory interhemispheric influences produced via transcallosal pathways. The two hemispheres are thought to mutually hamper neuroplastic reorganization of the other hemisphere. The results of preceding degeneration and neuroplastic reorganization of white matter may be reflected by Diffusion Tensor Imaging-derived diffusivity parameters such as fractional anisotropy (FA). In this study, we applied Diffusion Tensor Imaging (DTI) to contrast the white matter status of the contralesional hemisphere of young lesioned brains with and without contralateral influences by comparing patients after hemispherotomy to those who had not undergone neurosurgery. DTI was applied to 43 healthy controls (26 females, mean age ± SD: 25.07 ± 11.33 years) and two groups of in total 51 epilepsy patients with comparable juvenile brain lesions (32 females, mean age ± SD: 25.69 ± 12.77 years) either after hemispherotomy (30 of 51 patients) or without neurosurgery (21 of 51 patients), respectively. FA values were compared between these groups using the unbiased tract-based spatial statistics approach. A voxel-wise ANCOVA controlling for age at scan yielded significant group differences in FA. A post hoc t-test between hemispherotomy patients and healthy controls revealed widespread supra-threshold voxels in the contralesional hemisphere of hemispherotomy patients indicating comparatively higher FA values (p < 0.05, FWE-corrected). The non-surgery group, in contrast, showed extensive supra-threshold voxels indicating lower FA values in the contralesional hemisphere as compared to healthy controls (p < 0.05, FWE-corrected). Whereas lower FA values are suggestive of pronounced contralesional degeneration in the non-surgery group, higher FA values in the hemispherotomy group may be interpreted as a result of preceding plastic remodeling. We conclude that, whether juvenile brain lesions are associated with contralesional degeneration or reorganization partly depends on the ipsilesional hemisphere. Contralesional reorganization as observed in hemispherotomy patients was most likely enabled by the complete neurosurgical deafferentation of the ipsilesional hemisphere and, thereby, the disinhibition of the neuroplastic potential of the contralesional hemisphere. The main argument of this study is that hemispherotomy may be seen as a major plastic stimulus and as a prerequisite for contralesional neuroplastic remodeling in patients with juvenile brain lesions.
Liebers, Nora ; Düll, Johannes ; Fitzgerald, Donnacha ; Kerkhoff, Andrea ; Nörenberg, Daniel ; Käbisch, Eva ; Acker, Fabian ; Fuhrmann, Stephan ; Leng, Corinna ; Welslau, Manfred ; Chemnitz, Jens ; Middeke, Jan Moritz ; Weber, Thomas ; Holtick, Udo ; Trappe, Ralf Ulrich ; Pfannes, Roald ; Liersch, Rüdiger ; Spoer, Christian ; Fuxius, Stefan ; Gebauer, Niklas ; Caillé, Léandra ; Geer, Thomas ; Könecke, Christian ; Keller, Ulrich ; Claus, Rainer ; Mougiakakos, Dimitrios ; Mayer, Stephanie ; Hüttmann, Andreas ; Pott, Christiane ; Trummer, Arne ; Wulf, Gerald ; Brunnberg, Uta ; Bullinger, Lars ; Heß, Georg ; Müller-Tidow, Carsten ; Glaß, Bertram ; Lenz, Georg ; Dreger, Peter ; Dietrich, Sascha
The antibody-drug conjugate polatuzumab vedotin (pola) has recently been approved in combination with bendamustine and rituximab (pola-BR) for patients with refractory or relapsed (r/r) large B-cell lymphoma (LBCL). To investigate the efficacy of pola-BR in a real-world setting, we retrospectively analyzed 105 patients with LBCL who were treated in 26 German centers under the national compassionate use program. Fifty-four patients received pola as a salvage treatment and 51 patients were treated with pola with the intention to bridge to chimeric antigen receptor (CAR) T-cell therapy (n = 41) or allogeneic hematopoietic cell transplantation (n = 10). Notably, patients in the salvage and bridging cohort had received a median of 3 prior treatment lines. In the salvage cohort, the best overall response rate was 48.1%. The 6-month progression-free survival and overall survival (OS) was 27.7% and 49.6%, respectively. In the bridging cohort, 51.2% of patients could be successfully bridged with pola to the intended CAR T-cell therapy. The combination of pola bridging and successful CAR T-cell therapy resulted in a 6-month OS of 77.9% calculated from pola initiation. Pola vedotin-rituximab without a chemotherapy backbone demonstrated encouraging overall response rates up to 40%, highlighting both an appropriate alternative for patients unsuitable for chemotherapy and a new treatment option for bridging before leukapheresis in patients intended for CAR T-cell therapy. Furthermore, 7 of 12 patients with previous failure of CAR T-cell therapy responded to a pola-containing regimen. These findings suggest that pola may serve as effective salvage and bridging treatment of r/r LBCL patients.
Weber, Heike ; Scholz, Claus Jürgen ; Domschke, Katharina ; Baumann, Christian ; Klauke, Benedikt ; Jacob, Christian P. ; Maier, Wolfgang ; Fritze, Jürgen ; Bandelow, Borwin ; Zwanzger, Peter M. ; Lang, Thomas ; Fehm, Lydia ; Ströhle, Andreas ; Hamm, Alfons ; Gerlach, Alexander ; Alpers, Georg W. ; Kircher, Tilo ; Wittchen, Hans-Ulrich ; Arolt, Volker ; Pauli, Paul ; Deckert, Jürgen ; Reif, Andreas
Background: Panic disorder is common (5% prevalence) and females are twice as likely to be affected as males. The heritable component of panic disorder is estimated at 48%. Glutamic acid dehydrogenase GAD1, the key enzyme for the synthesis of the inhibitory and anxiolytic neurotransmitter GABA, is supposed to influence various mental disorders, including mood and anxiety disorders. In a recent association study in depression, which is highly comorbid with panic disorder, GAD1 risk allele associations were restricted to females.
Methodology/Principal Findings: Nineteen single nucleotide polymorphisms (SNPs) tagging the common variation in GAD1 were genotyped in two independent gender and age matched case-control samples (discovery sample n = 478; replication sample n = 584). Thirteen SNPs passed quality control and were examined for gender-specific enrichment of risk alleles associated with panic disorder by using logistic regression including a genotype×gender interaction term. The latter was found to be nominally significant for four SNPs (rs1978340, rs3762555, rs3749034, rs2241165) in the discovery sample; of note, the respective minor/risk alleles were associated with panic disorder only in females. These findings were not confirmed in the replication sample; however, the genotype×gender interaction of rs3749034 remained significant in the combined sample. Furthermore, this polymorphism showed a nominally significant association with the Agoraphobic Cognitions Questionnaire sum score.
Conclusions/Significance: The present study represents the first systematic evaluation of gender-specific enrichment of risk alleles of the common SNP variation in the panic disorder candidate gene GAD1. Our tentative results provide a possible explanation for the higher susceptibility of females to panic disorder.
Lal, Dennis ; Ruppert, Ann-Kathrin ; Trucks, Holger ; Schulz, Herbert ; Kovel, Carolien G. de ; Kasteleijn-Nolst Trenité, Dorothée G. ; Sonsma, Anja C. M. ; Koeleman, Bobby P. ; Lindhout, Dick ; Weber, Yvonne G. ; Lerche, Holger ; Kapser, Claudia ; Schankin, Christoph Josef ; Kunz, Wolfram S. ; Surges, Rainer ; Elger, Christian Erich ; Gaus, Verena ; Schmitz, Bettina ; Helbig, Ingo ; Muhle, Hiltrud ; Stephani, Ulrich ; Klein, Karl Martin ; Rosenow, Felix ; Neubauer, Bernd Axel ; Reinthaler, Eva Maria ; Zimprich, Fritz ; Feucht, Martha ; Møller, Rikke S. ; Hjalgrim, Helle ; Jonghe, Peter De ; Suls, Arvid ; Lieb, Wolfgang ; Franke, Andre ; Strauch, Konstantin ; Gieger, Christian ; Schurmann, Claudia ; Schminke, Ulf ; Nürnberg, Peter ; Sander, Thomas
Genetic generalised epilepsy (GGE) is the most common form of genetic epilepsy, accounting for 20% of all epilepsies. Genomic copy number variations (CNVs) constitute important genetic risk factors of common GGE syndromes. In our present genome-wide burden analysis, large (≥ 400 kb) and rare (< 1%) autosomal microdeletions with high calling confidence (≥ 200 markers) were assessed by the Affymetrix SNP 6.0 array in European case-control cohorts of 1,366 GGE patients and 5,234 ancestry-matched controls. We aimed to: 1) assess the microdeletion burden in common GGE syndromes, 2) estimate the relative contribution of recurrent microdeletions at genomic rearrangement hotspots and non-recurrent microdeletions, and 3) identify potential candidate genes for GGE. We found a significant excess of microdeletions in 7.3% of GGE patients compared to 4.0% in controls (P = 1.8 x 10-7; OR = 1.9). Recurrent microdeletions at seven known genomic hotspots accounted for 36.9% of all microdeletions identified in the GGE cohort and showed a 7.5-fold increased burden (P = 2.6 x 10-17) relative to controls. Microdeletions affecting either a gene previously implicated in neurodevelopmental disorders (P = 8.0 x 10-18, OR = 4.6) or an evolutionarily conserved brain-expressed gene related to autism spectrum disorder (P = 1.3 x 10-12, OR = 4.1) were significantly enriched in the GGE patients. Microdeletions found only in GGE patients harboured a high proportion of genes previously associated with epilepsy and neuropsychiatric disorders (NRXN1, RBFOX1, PCDH7, KCNA2, EPM2A, RORB, PLCB1). Our results demonstrate that the significantly increased burden of large and rare microdeletions in GGE patients is largely confined to recurrent hotspot microdeletions and microdeletions affecting neurodevelopmental genes, suggesting a strong impact of fundamental neurodevelopmental processes in the pathogenesis of common GGE syndromes.
Partial wave analysis of the reaction p(3.5 GeV) + p → pK +Λ to search for the "ppK−" bound state
(2015)
Agakishiev, Geydar ; Arnold, Oliver Werner ; Belver, Daniel ; Belyaev, A. ; Berger-Chen, Jia-Chii ; Blanco, Alberto ; Böhmer, Michael ; Boyard, Jean-Louis ; Cabanelas Eiras, Pablo ; Chernenko, Sergey P. ; Dybczak, Adrian ; Epple, Eliane ; Fabbietti, Laura ; Fateev, Oleg ; Finocchiaro, Paolo ; Fonte, Paulo ; Friese, Jürgen ; Fröhlich, Ingo ; Galatyuk, Tetyana ; Garzón, Juan A. ; Gernhäuser, Roman ; Göbel, Kathrin ; Golubeva, Marina ; González-Díaz, Diégo ; Guber, Fedor ; Gumberidze, Malgorzata ; Heinz, T. ; Hennino, Thierry ; Holzmann, Romain ; Ierusalimov, Alexander P. ; Iori, Ileana ; Ivashkin, Alexander ; Jurkovič, Martin ; Kämpfer, Burkhard ; Karavicheva, Tatiana L. ; Koenig, Ilse ; Koenig, W. ; Kolb, Burkhard W. ; Kornakov, Georgy ; Kotte, Roland ; Krása, Antonin ; Krizek, Filip ; Krücken, Reiner ; Kuc, Hubert ; Kühn, Wolfgang ; Kugler, Andrej ; Kunz, Tobias ; Kurepin, Alexander ; Ladygin, Vladimir P. ; Lalik, Rafał Tomasz ; Lapidus, Kirill ; Lebedev, Alexei ; Lopes, Luis Alberto Vieira ; Lorenz, Manuel ; Maier, Ludwig W. ; Mangiarotti, Alessio ; Markert, Jochen ; Metag, Volker ; Michel, Jan ; Müntz, Christian ; Münzer, Robert Helmut ; Naumann, Lothar ; Pachmayer, Yvonne C. ; Palka, Marek ; Parpottas, Yannis ; Pechenov, Vladimir ; Pechenova, Olga ; Pietraszko, Jerzy ; Przygoda, Witold ; Ramstein, Béatrice ; Reshetin, Andrey ; Rustamov, Anar ; Sadovsky, Alexander ; Salabura, Piotr ; Schmah, Alexander ; Schwab, Erwin ; Siebenson, Johannes Stephan ; Sobolev, Yuri G. ; Spataro, Stefano ; Spruck, Björn ; Ströbele, Herbert ; Stroth, Joachim ; Sturm, C. ; Tarantola Peloni, Attilio ; Teilab, Khaled ; Tlustý, Pavel ; Traxler, Michael ; Tsertos, Haralabos ; Vasiliev, Taras A. ; Wagner, Vladimir ; Weber, Michael ; Wendisch, Christian ; Wüstenfeld, Jörn ; Yurevich, Sergey ; Zanevsky, Yuri V. ; Sarantsev, Andrei V.
Employing the Bonn–Gatchina partial wave analysis framework (PWA), we have analyzed HADES data of the reaction p(3.5 GeV) + p → pK +Λ. This reaction might contain information about the kaonic cluster “ppK −” (with quantum numbers J P = 0− and total isospin I = 1/2) via its decay into pΛ. Due to interference effects in our coherent description of the data, a hypothetical KNN (or, specifically “ppK −”) cluster signal need not necessarily show up as a pronounced feature (e.g. a peak) in an invariant mass spectrum like pΛ. Our PWA analysis includes a variety of resonant and non-resonant intermediate states and delivers a good description of our data (various angular distributions and two-hadron invariant mass spectra) without a contribution of a KNN cluster. At a confidence level of CLs = 95% such a cluster cannot contribute more than 2–12% to the total cross section with a pK +Λ final state, which translates into a production cross-section between 0.7 μb and 4.2 μb, respectively. The range of the upper limit depends on the assumed cluster mass, width and production process.
Mutlak, Haitham ; Weber, Christian Friedrich ; Meininger, Dirk ; Cuca, Colleen ; Zacharowski, Kai ; Byhahn, Christian ; Schalk, Richard
OBJECTIVE: The role of supraglottic airway devices in emergency airway management is highlighted in international airway management guidelines. We evaluated the application of the new generation laryngeal tube suction (LTS-II/LTS-D) in the management of in-hospital unexpected difficult airway and cardiopulmonary resuscitation.
METHODS: During a seven-year period, patients treated with a laryngeal tube who received routine anesthesia and had an unexpected difficult airway (Cormack Lehane Grade 3-4), who underwent cardiopulmonary resuscitation, or who underwent cardiopulmonary resuscitation outside the operating room and had a difficult airway were evaluated. Successful placement of the LTS II/LTS-D, sufficient ventilation, time to placement, number of placement attempts, stomach content, peripheral oxygen saturation/end-tidal carbon dioxide development (SpO2/etCO2) over 5 minutes, subjective overall assessment and complications were recorded.
RESULTS: In total, 106 adult patients were treated using an LTS-II/LTS-D. The main indication for placement was a difficult airway (75%, n=80), followed by cardiopulmonary resuscitation (25%, n=26) or an overlap between both (18%, n=19). In 94% of patients (n=100), users placed the laryngeal tube during the first attempt. In 93% of patients (n=98), the tube was placed within 30 seconds. A significant increase in SpO2 from 97% (0-100) to 99% (5-100) was observed in the whole population and in cardiopulmonary resuscitation patients. The average initial etCO2 of 39.5 mmHg (0-100 mmHg) decreased significantly to an average of 38.4 mmHg (10-62 mmHg) after 5 minutes. A comparison of cardiopulmonary resuscitation patients with non-cardiopulmonary resuscitation patients regarding gastric contents showed no significant difference.
CONCLUSIONS: LTS-D/LTS-II use for in-hospital unexpected difficult airway management provides a secure method for primary airway management until other options such as video laryngoscopy or fiber optic intubation become available.
Bravina, Larissa ; Zabrodin, Eugene E. ; Bass, Steffen A. ; Fäßler, Amand ; Fuchs, Christian ; Gorenstein, Mark I. ; Greiner, Walter ; Soff, Sven ; Stöcker, Horst ; Weber, Henning
The relaxation of hot nuclear matter to an equilibrated state in the central zone of heavy-ion collisions at energies from AGS to RHIC is studied within the microscopic UrQMD model. It is found that the system reaches the (quasi)equilibrium stage for the period of 10-15 fm/c. Within this time the matter in the cell expands nearly isentropically with the entropy to baryon ratio S/A = 150 - 170. Thermodynamic characteristics of the system at AGS and at SPS energies at the endpoints of this stage are very close to the parameters of chemical and thermal freeze-out extracted from the thermal fit to experimental data. Predictions are made for the full RHIC energy square root s = 200$ AGeV. The formation of a resonance-rich state at RHIC energies is discussed.
Relativistic hadron-hadron collisions in the ultra-relativistic quantum molecular dynamics model
(1999)
Bleicher, Marcus ; Zabrodin, Eugene E. ; Spieles, Christian ; Bass, Steffen A. ; Ernst, Christoph ; Soff, Sven ; Bravina, Larissa ; Belkacem, Mohamed ; Weber, H. ; Stöcker, Horst ; Greiner, Walter
Hadron-hadron collisions at high energies are investigated in the Ultra- relativistic-Quantum-Molecular-Dynamics approach. This microscopic trans- port model describes the phenomenology of hadronic interactions at low and intermediate energies ( s < 5 GeV) in terms of interactions between known hadrons and their resonances. At higher energies, s > 5 GeV, the excitation of color strings and their subsequent fragmentation into hadrons dominates the multiple production of particles in the UrQMD model. The model shows a fair overall agreement with a large body of experimental h-h data over a wide range of h-h center-of-mass energies. Hadronic reaction data with higher precision would be useful to support the use of the UrQMD model for relativistic heavy ion collisions.
Bravina, Larissa ; Gorenstein, Mark I. ; Zabrodin, Eugene E. ; Bass, Steffen A. ; Belkacem, Mohamed ; Bleicher, Marcus ; Brandstetter, Mathias ; Hofmann, Markus ; Soff, Sven ; Spieles, Christian ; Weber, H. ; Stöcker, Horst ; Greiner, Walter
Abstract: Local thermal and chemical equilibration is studied for central AqA collisions at 10.7 160 AGeV in the Ultrarelativis- . tic Quantum Molecular Dynamics model UrQMD . The UrQMD model exhibits strong deviations from local equilibrium at the high density hadron string phase formed during the early stage of the collision. Equilibration of the hadron resonance matter is established in the central cell of volume Vs125 fm3 at later stages, tG10 fmrc, of the resulting quasi-isentropic expansion. The thermodynamical functions in the cell and their time evolution are presented. Deviations of the UrQMD quasi-equilibrium state from the statistical mechanics equilibrium are found. They increase with energy per baryon and lead to a strong enhancement of the pion number density as compared to statistical mechanics estimates at SPS energies. PACS: 25.75.-q; 24.10.Lx; 24.10.Pa; 64.30.qt
Bleicher, Marcus ; Bass, Steffen A. ; Belkacem, Mohamed ; Brachmann, Jörg ; Brandstetter, Mathias ; Ernst, Christoph ; Gerland, Lars ; Konopka, Jens ; Soff, Sven ; Spieles, Christian ; Weber, Henning ; Stöcker, Horst ; Greiner, Walter
Microscopic calculations of central collisions between heavy nuclei are used to study fragment production and the creation of collective flow. It is shown that the final phase space distributions are compatible with the expectations from a thermally equilibrated source, which in addition exhibits a collective transverse expansion. However, the microscopic analyses of the transient states in the reaction stages of highest density and during the expansion show that the system does not reach global equilibrium. Even if a considerable amount of equilibration is assumed, the connection of the measurable final state to the macroscopic parameters, e.g. the temperature, of the transient "equilibrium" state remains ambiguous.
Bass, Steffen A. ; Weber, Henning ; Ernst, Christoph ; Bleicher, Marcus ; Belkacem, Mohamed ; Bravina, Larissa ; Soff, Sven ; Stöcker, Horst ; Greiner, Walter ; Spieles, Christian
We analyze the reaction dynamics of central Pb+Pb collisions at 160 GeV/nucleon. First we estimate the energy density pile-up at mid-rapidity and calculate its excitation function: The energy density is decomposed into hadronic and partonic contributions. A detailed analysis of the collision dynamics in the framework of a microscopic transport model shows the importance of partonic degrees of freedom and rescattering of leading (di)quarks in the early phase of the reaction for E >= 30 GeV/nucleon. The energy density reaches up to 4 GeV/fm 3, 95% of which are contained in partonic degrees of freedom. It is shown that cells of hadronic matter, after the early reaction phase, can be viewed as nearly chemically equilibrated. This matter never exceeds energy densities of 0.4 GeV/fm 3, i.e. a density above which the notion of separated hadrons loses its meaning. The final reaction stage is analyzed in terms of hadron ratios, freeze-out distributions and a source analysis for final state pions.
Bravina, Larissa ; Gorenstein, Mark I. ; Belkacem, Mohamed ; Bass, Steffen A. ; Bleicher, Marcus ; Brandstetter, Mathias ; Hofmann, M. ; Soff, Sven ; Spieles, Christian ; Weber, Henning ; Stöcker, Horst ; Greiner, Walter
Local kinetic and chemical equilibration is studied for Au+Au collisions at 10.7 AGeV in the microscopic Ultrarelativistic Quantum Molecular Dynamics model (UrQMD). The UrQMD model exhibits dramatic deviations from equilibrium during the high density phase of the collision. Thermal and chemical equilibration of the hadronic matter seems to be established in the later stages during a quasiisentropic expansion, observed in the central reaction cell with volume 125 fm3. For t > 10 fm/c the hadron energy spectra in the cell are nicely reproduced by Boltzmann distributions with a common rapidly dropping temperature. Hadron yields change drastically and at the late expansion stage follow closely those of an ideal gas statistical model. The equation of state seems to be simple at late times: P = 0.12 Epsilon. The time evolution of other thermodynamical variables in the cell is also presented.
Belkacem, Mohamed ; Brandstetter, Mathias ; Bass, Steffen A. ; Bleicher, Marcus ; Bravina, Larissa ; Gorenstein, Mark I. ; Konopka, Jens ; Neise, Ludwig ; Spieles, Christian ; Soff, Sven ; Weber, Henning ; Stöcker, Horst ; Greiner, Walter
Equilibrium properties of infinite relativistic hadron matter are investigated using the Ultrarelativistic Quantum Molecular Dynamics (UrQMD) model. The simulations are performed in a box with periodic boundary conditions. Equilibration times depend critically on energy and baryon densities. Energy spectra of various hadronic species are shown to be isotropic and consistent with a single temperature in equilibrium. The variation of energy density versus temperature shows a Hagedorn-like behavior with a limiting temperature of 130 +/- 10 MeV. Comparison of abundances of different particle species to ideal hadron gas model predictions show good agreement only if detailed balance is implemented for all channels. At low energy densities, high mass resonances are not relevant; however, their importance raises with increasing energy density. The relevance of these different conceptual frameworks for any interpretation of experimental data is questioned.
Bass, Steffen A. ; Belkacem, Mohamed ; Brandstetter, Mathias ; Bleicher, Marcus ; Gerland, Lars ; Konopka, Jens ; Neise, Ludwig ; Spieles, Christian ; Soff, Sven ; Weber, Henning ; Stöcker, Horst ; Greiner, Walter
Ratios of hadronic abundances are analyzed for pp and nucleus-nucleus collisions at sqrt(s)=20 GeV using the microscopic transport model UrQMD. Secondary interactions significantly change the primordial hadronic cocktail of the system. A comparison to data shows a strong dependence on rapidity. Without assuming thermal and chemical equilibrium, predicted hadron yields and ratios agree with many of the data, the few observed discrepancies are discussed.
Konopka, Jens ; Bass, Steffen A. ; Bleicher, Marcus ; Brandstetter, Mathias ; Ernst, Christoph ; Gerland, Lars ; Greiner, Walter ; Soff, Sven ; Spieles, Christian ; Stöcker, Horst ; Weber, Henning ; Winckelmann, Luke Andreas
Quantum Molecular Dynamics (QMD) calculations of central collisions between heavy nuclei are used to study fragment production and the creation of collective flow. It is shown that the final phase space distributions are compatible with the expectations from a thermally equilibrated source, which in addition exhibits a collective transverse expansion. However, the microscopic analyses of the transient states in the intermediate reaction stages show that the event shapes are more complex and that equilibrium is reached only in very special cases but not in event samples which cover a wide range of impact parameters as it is the case in experiments. The basic features of a new molecular dynamics model (UQMD) for heavy ion collisions from the Fermi energy regime up to the highest presently available energies are outlined.
Zschiesche, Detlef ; Bass, Steffen A. ; Bleicher, Marcus ; Brachmann, Jörg ; Gerland, Lars ; Paech, Kerstin ; Scherer, Stefan ; Soff, Sven ; Spieles, Christian ; Weber, Henning ; Stöcker, Horst ; Greiner, Walter
Compelling evidence for the creation of a new form of matter has been claimed to be found in Pb+Pb collisions at SPS. We discuss the uniqueness of often proposed experimental signatures for quark matter formation in relativistic heavy ion collisions. It is demonstrated that so far none of the proposed signals like J/psi meson production/suppression, strangeness enhancement, dileptons, and directed flow unambigiously show that a phase of deconfined matter has been formed in SPS Pb+Pb collisions. We emphasize the need for systematic future measurements to search for simultaneous irregularities in the excitation functions of several observables in order to come close to pinning the properties of hot, dense QCD matter from data.
Bass, Steffen A. ; Belkacem, Mohamed ; Bleicher, Marcus ; Brandstetter, Mathias ; Bravina, Larissa ; Ernst, Christoph ; Gerland, Lars ; Hofmann, Max ; Hofmann, Sigurd ; Konopka, Jens ; Mao, Guangjun ; Neise, Ludwig ; Soff, Sven ; Spieles, Christian ; Weber, Henning ; Winckelmann, Luke Andreas ; Stöcker, Horst ; Greiner, Walter ; Hartnack, Christoph ; Aichelin, Jörg ; Amelin, Nikolai
In this paper, the concepts of microscopic transport theory are introduced and the features and shortcomings of the most commonly used ansatzes are discussed. In particular, the Ultrarelativistic Quantum Molecular Dynamics (UrQMD) transport model is described in great detail. Based on the same principles as QMD and RQMD, it incorporates a vastly extended collision term with full baryon-antibaryon symmetry, 55 baryon and 32 meson species. Isospin is explicitly treated for all hadrons. The range of applicability stretches from E lab < 100$ MeV/nucleon up to E lab> 200$ GeV/nucleon, allowing for a consistent calculation of excitation functions from the intermediate energy domain up to ultrarelativistic energies. The main physics topics under discussion are stopping, particle production and collective flow.
Bleicher, Marcus ; Belkacem, Mohamed ; Ernst, Christoph ; Weber, Henning ; Gerland, Lars ; Spieles, Christian ; Bass, Steffen A. ; Stöcker, Horst ; Greiner, Walter
We perform an event-by-event analysis of the transverse momentum distribution of final state particles in central Pb(160AGeV)+Pb collisions within a microscopic non-equilibrium transport model (UrQMD). Strong influence of rescattering is found. The extracted momentum distributions show less fluctuations in A+A collisions than in p+p reactions. This is in contrast to simplified p+p extrapolations and random walk models.
Weber, H. ; Ernst, Christoph ; Bleicher, Marcus ; Bravina, Larissa ; Stöcker, Horst ; Greiner, Walter ; Spieles, Christian ; Bass, Steffen A.
We estimate the energy density epsilon pile-up at mid-rapidity in central Pb+Pb collisions from 2 200 GeV/nucleon. epsilon is decomposed into hadronic and partonic contributions. A detailed analysis of the collision dynamics in the framework of a microscopic transport model shows the importance of partonic degrees of freedom and rescattering of leading (di)quarks in the early phase of the reaction for Elab 30 GeV/nucleon. In Pb+Pb collisions at 160 GeV/nucleon the energy density reaches up to 4 GeV/fm3, 95% of which are contained in partonic degrees of freedom.
Maraslioglu, Miriam ; Oppermann, Elsie ; Blattner, Carolin ; Weber, Roxane ; Henrich, Dirk ; Jobin, Christian ; Schleucher, Elke ; Marzi, Ingo ; Lehnert, Mark
Chronic ethanol abuse is known to increase susceptibility to infections after injury, in part, by modification of macrophage function. Several intracellular signalling mechanisms are involved in the initiation of inflammatory responses, including the nuclear factor-κB (NF-κB) pathway. In this study, we investigated the systemic and hepatic effect of chronic ethanol feeding on in vivo activation of NF-κB in NF-κB(EGFP) reporter gene mice. Specifically, the study focused on Kupffer cell proinflammatory cytokines IL-6 and TNF-α and activation of NF-κB after chronic ethanol feeding followed by in vitro stimulation with lipopolysaccharide (LPS). We found that chronic ethanol upregulated NF-κB activation and increased hepatic and systemic proinflammatory cytokine levels. Similarly, LPS-stimulated IL-1 β release from whole blood was significantly enhanced in ethanol-fed mice. However, LPS significantly increased IL-6 and TNF-α levels. These results demonstrate that chronic ethanol feeding can improve the responsiveness of macrophage LPS-stimulated IL-6 and TNF-α production and indicate that this effect may result from ethanol-induced alterations in intracellular signalling through NF-κB. Furthermore, LPS and TNF-α stimulated the gene expression of different inflammatory mediators, in part, in a NF-κB-dependent manner.
THIS PROJECT PROVIDES A PERFORMANCE MEASURE ON THE EFFECT OF LATENCY IN THE CONTEXT OF THE COMPETITIVE ADVANTAGE OF IT. BASED ON A DATASET OF DEUTSCHE BÖRSE’S ELECTRONIC TRADING SYSTEM XETRA, AN EMPIRICAL ANALYSIS IS APPLIED. THAT WAY, WE QUANTIFY THE IMPACT OF LATENCY FROM A CUSTOMER’S POINT OF VIEW.
Prillwitz, Conrad ; David, Bastian ; Schlaug, Gottfried ; Deller, Thomas ; Schramm, Johannes ; Lindenberg, Robert ; Hattingen, Elke ; Weber, Bernd ; Surges, Rainer ; Elger, Christian Erich ; Rüber, Theodor
Objective: Using multimodal imaging, we tested the hypothesis that patients after hemispherotomy recruit non-primary motor areas and non-pyramidal descending motor fibers to restore motor function of the impaired limb. Methods: Functional and structural MRI data were acquired in a group of 25 patients who had undergone hemispherotomy and in a matched group of healthy controls. Patients’ motor impairment was measured using the Fugl-Meyer Motor Assessment. Cortical areas governing upper extremity motor-control were identified by task-based functional MRI. The resulting areas were used as nodes for functional and structural connectivity analyses. Results: In hemispherotomy patients, movement of the impaired upper extremity was associated to widespread activation of non-primary premotor areas, whereas movement of the unimpaired one and of the control group related to activations prevalently located in the primary motor cortex (all p ≤ 0.05, FWE-corrected). Non-pyramidal tracts originating in premotor/supplementary motor areas and descending through the pontine tegmentum showed relatively higher structural connectivity in patients (p < 0.001, FWE-corrected). Significant correlations between structural connectivity and motor impairment were found for non-pyramidal (p = 0.023, FWE-corrected), but not for pyramidal connections. Interpretation: A premotor/supplementary motor network and non-pyramidal fibers seem to mediate motor function in patients after hemispherotomy. In case of hemispheric lesion, the homologous regions in the contralesional hemisphere may not compensate the resulting motor deficit, but the functionally redundant premotor network.
Stevic, Ines ; Müller, Volkmar ; Weber, Karsten E. ; Fasching, Peter Andreas ; Karn, Thomas ; Marmé, Frederic ; Schem, Christian ; Stickeler, Elmar ; Denkert, Carsten Michael ; Mackelenbergh, Marion Tina van ; Salat, Christoph ; Schneeweiss, Andreas ; Pantel, Klaus ; Loibl, Sibylle ; Untch, Michael ; Schwarzenbach, Heidi
Background: The focus of this study is to identify particular microRNA (miRNA) signatures in exosomes derived from plasma of 435 human epidermal growth factor receptor 2 (HER2)-positive and triple-negative (TN) subtypes of breast cancer (BC).
Methods: First, miRNA expression profiles were determined in exosomes derived from the plasma of 15 TNBC patients before neoadjuvant therapy using a quantitative TaqMan real-time PCR-based microRNA array card containing 384 different miRNAs. Forty-five miRNAs associated with different clinical parameters were then selected and mounted on microRNA array cards that served for the quantification of exosomal miRNAs in 435 BC patients before therapy and 20 healthy women. Confocal microscopy, Western blot, and ELISA were used for exosome characterization.
Results: Quantification of 45 exosomal miRNAs showed that compared with healthy women, 10 miRNAs in the entire cohort of BC patients, 13 in the subgroup of 211 HER2-positive BC, and 17 in the subgroup of 224 TNBC were significantly deregulated. Plasma levels of 18 exosomal miRNAs differed between HER2-positive and TNBC subtypes, and 9 miRNAs of them also differed from healthy women. Exosomal miRNAs were significantly associated with the clinicopathological and risk factors. In uni- and multivariate models, miR-155 (p = 0.002, p = 0.003, respectively) and miR-301 (p = 0.002, p = 0.001, respectively) best predicted pathological complete response (pCR).
Conclusion: Our findings show a network of deregulated exosomal miRNAs with specific expression patterns in exosomes of HER2-positive and TNBC patients that are also associated with clinicopathological parameters and pCR within each BC subtype.
Weber, Axel ; Borghouts, Corina ; Brendel, Christian ; Moriggl, Richard ; Delis, Natalia ; Brill, Boris ; Vafaizadeh, Vida ; Groner, Bernd
Signal transducers and activators of transcription (Stats) play central roles in the conversion of extracellular signals, e.g., cytokines, hormones and growth factors, into tissue and cell type specific gene expression patterns. In normal cells, their signaling potential is strictly limited in extent and duration. The persistent activation of Stat3 or Stat5 is found in many human tumor cells and contributes to their growth and survival. Stat5 activation plays a pivotal role in nearly all hematological malignancies and occurs downstream of oncogenic kinases, e.g., Bcr-Abl in chronic myeloid leukemias (CML) and Jak2(V617F) in other myeloproliferative diseases (MPD). We defined the mechanisms through which Stat5 affects growth and survival of K562 cells, representative of Bcr-Abl positive CML, and HEL cells, representative for Jak2(V617F) positive acute erythroid leukemia. In our experiments we suppressed the protein expression levels of Stat5a and Stat5b through shRNA mediated downregulation and demonstrated the dependence of cell survival on the presence of Stat5. Alternatively, we interfered with the functional capacities of the Stat5 protein through the interaction with a Stat5 specific peptide ligand. This ligand is a Stat5 specific peptide aptamer construct which comprises a 12mer peptide integrated into a modified thioredoxin scaffold, S5-DBD-PA. The peptide sequence specifically recognizes the DNA binding domain (DBD) of Stat5. Complex formation of S5-DBD-PA with Stat5 causes a strong reduction of P-Stat5 in the nuclear fraction of Bcr-Abl-transformed K562 cells and a suppression of Stat5 target genes. Distinct Stat5 mediated survival mechanisms were detected in K562 and Jak2(V617F)-transformed HEL cells. Stat5 is activated in the nuclear and cytosolic compartments of K562 cells and the S5-DBD-PA inhibitor most likely affects the viability of Bcr-Abl+ K562 cells through the inhibition of canonical Stat5 induced target gene transcription. In HEL cells, Stat5 is predominantly present in the cytoplasm and the survival of the Jak2(V617F)+ HEL cells is impeded through the inhibition of the cytoplasmic functions of Stat5.
Weber, Axel ; Borghouts, Corina ; Brendel, Christian ; Moriggl, Richard ; Delis, Natalia ; Brill, Boris ; Vafaizadeh, Vida ; Groner, Bernd
The signal transducer and activator of transcription Stat5 is transiently activated by growth factor and cytokine signals in normal cells, but its persistent activation has been observed in a wide range of human tumors. Aberrant Stat5 activity was initially observed in leukemias, but subsequently also found in carcinomas. We investigated the importance of Stat5 in human tumor cell lines. shRNA mediated downregulation of Stat5 revealed the dependence of prostate and breast cancer cells on the expression of this transcription factor. We extended these inhibition studies and derived a peptide aptamer (PA) ligand, which directly interacts with the DNA-binding domain of Stat5 in a yeast-two-hybrid screen. The Stat5 specific PA sequence is embedded in a thioredoxin (hTRX) scaffold protein. The resulting recombinant protein S5-DBD-PA was expressed in bacteria, purified and introduced into tumor cells by protein transduction. Alternatively, S5-DBD-PA was expressed in the tumor cells after infection with a S5-DBD-PA encoding gene transfer vector. Both strategies impaired the DNA-binding ability of Stat5, suppressed Stat5 dependent transactivation and caused its intracellular degradation. Our experiments describe a peptide based inhibitor of Stat5 protein activity which can serve as a lead for the development of a clinically useful compound for cancer treatment.
Raimann, Florian ; Lindner, Gesche Marie-Louise ; Martin, Christoph ; Jennewein, Lukas ; Lustenberger, Thomas ; Piekarski, Florian ; Zacharowski, Kai ; Weber, Christian Friedrich
Background: Acute bleeding requires fast and targeted therapy. Therefore, knowledge of the patient's potential to form a clot is crucial. Point-of-care testing (POCT) provides fast and reliable information on coagulation. Structural circumstances, such as person-bound sample transport, can prolong the reporting of the results. The aim of the present study was to investigate the diagnostic quality and accuracy between POCT INR diagnostics and standard laboratory analysis (SLA) as well as the time advantage between a pneumatic tube and a personal-based transport system. Methods: Two groups of haemorrhagic patients (EG: emergency department; OG: delivery room; each n = 12) were examined in the context of bleeding emergencies using POCT and SLA. Samples were transported via a pneumatic tube system or by a personal transport service. Results: INR results between POCT and SLA showed a high and significant correlation (EG: p < 0.001; OG: p < 0.001). POCT results were reported significantly more quickly (EG: 1.1 vs. 39.6 min; OG: 2.0 vs. 75.0 min; p < 0.001) and required less time for analysis (EG: 0.3 vs. 24.0 min; OG: 0.5 vs. 45.0 min; p < 0.001) compared to SLA. The time for transportation with the pneumatic tube was significantly shorter (8.0 vs. 18.5 min; p < 0.001) than with the personal-based transport system. Conclusion: The results of the present study suggest that POCT may be a suitable method for the emergency diagnosis and may be used as prognostic diagnostic elements in haemotherapy algorithms to initiate targeted haemotherapy at an early point in time.
Grimm, Oliver ; Weber, Heike ; Kittel-Schneider, Sarah ; Kranz, Thorsten Manfred ; Jacob, Christian P. ; Lesch, Klaus-Peter J. ; Reif, Andreas
While impulsivity is a basic feature of attention-deficit / hyperactivity disorder (ADHD), no study explored the effect of different components of the Impulsiveness (Imp) and Venturesomeness (Vent) scale (IV7) on psychiatric comorbidities and an ADHD polygenic risk score (PRS). We used the IV7 self-report scale in an adult ADHD sample of 903 patients, 70% suffering from additional comorbid disorders, and in a subsample of 435 genotyped patients. Venturesomeness, unlike immediate Impulsivity, is not specific to ADHD. We consequently analyzed the influence of Imp and Vent also in the context of a PRS on psychiatric comorbidities of ADHD. Vent shows a distinctly different distribution of comorbidities, e.g., less anxiety and depression. PRS showed no effect on different ADHD comorbidities, but correlated with childhood hyperactivity. In a complementary analysis using principal component analysis with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition ADHD criteria, revised NEO Personality Inventory, Imp, Vent, and PRS, we identified three ADHD subtypes. These are an impulsive–neurotic type, an adventurous–hyperactive type with a stronger genetic component, and an anxious–inattentive type. Our study thus suggests the importance of adventurousness and the differential consideration of impulsivity in ADHD. The genetic risk is distributed differently between these subtypes, which underlines the importance of clinically motivated subtyping. Impulsivity subtyping might give insights into the organization of comorbid disorders in ADHD and different genetic background.
Häußler, Katja Susanne ; Keese, Michael ; Weber, Christian Friedrich ; Geisen, Christof ; Miesbach, Wolfgang
Postoperative thrombotic thrombocytopenic purpura (TTP) shows clinical presentation similar to classical TTP, whereas exact pathophysiological contexts remain unexplained. In this study, we investigated intraoperative and postoperative changes in ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type 1 motifs, member 13), von Willebrand factor (VWF), large VWF multimers, and interleukin-6 (IL-6) in vascular surgery patients. The objective was to compare the impact of endovascular, peripheral, and aortic surgery on target parameters which are supposed to play a role in surgery-associated TTP. A total of 93 vascular surgery patients were included and divided into 4 groups according to the specific type of intervention they underwent. Blood samples were taken preoperatively, intraoperatively, and postoperatively on days 2 and 4. The ADAMTS-13 activity decreased significantly in 3 of the 4 groups during surgery (from median 81% to 49%, P < .001, in the group undergoing aortoiliacal interventions), whereas the percentage of large VWF multimers increased in all groups of patients. von Willebrand factor antigen increased significantly in all groups on postoperative day 2 and IL-6 increased significantly in the intraoperative and early postoperative period. There was no significant correlation between the intraoperative decrease in ADAMTS-13 and the increase in VWF or IL-6. No patient in this study showed clinical picture of TTP; the precise cause and clinical significance of moderately reduced ADAMTS-13 activity in the perioperative setting have not yet been definitely determined.
Der eine gibt nur wenige Cents, der nächste lässt beim Trinkgeld etwas mehr springen. Am Extra-Obolus, der Rechnung plus X, scheiden sich die Geister. Ein Forschungsseminar an der Goethe-Universität hat zum Thema Trinkgeld ein Semester lang Gäste und Kellner/innen befragt – mit überraschenden Ergebnissen.
Berkner, Hanna ; Seutter von Loetzen, Christian ; Hartl, Maximilian ; Randow, Stefanie ; Gubesch, Michaela ; Vogel, Lothar ; Husslik, Felix ; Reuter, Andreas ; Lidholm, Jonas ; Ballmer-Weber, Barbara ; Vieths, Stefan ; Rösch, Paul ; Schiller, Dirk
Background: Birch pollen-allergic subjects produce polyclonal cross-reactive IgE antibodies that mediate pollen-associated food allergies. The major allergen Bet v 1 and its homologs in plant foods bind IgE in their native protein conformation. Information on location, number and clinical relevance of IgE epitopes is limited. We addressed the use of an allergen-related protein model to identify amino acids critical for IgE binding of PR-10 allergens.
Method: Norcoclaurine synthase (NCS) from meadow rue is structurally homologous to Bet v 1 but does not bind Bet v 1-reactive IgE. NCS was used as the template for epitope grafting. NCS variants were tested with sera from 70 birch pollen allergic subjects and with monoclonal antibody BV16 reported to compete with IgE binding to Bet v 1.
Results: We generated an NCS variant (Δ29NCSN57/I58E/D60N/V63P/D68K) harboring an IgE epitope of Bet v 1. Bet v 1-type protein folding of the NCS variant was evaluated by 1H-15N-HSQC NMR spectroscopy. BV16 bound the NCS variant and 71% (50/70 sera) of our study population showed significant IgE binding. We observed IgE and BV16 cross-reactivity to the epitope presented by the NCS variant in a subgroup of Bet v 1-related allergens. Moreover BV16 blocked IgE binding to the NCS variant. Antibody cross-reactivity depended on a defined orientation of amino acids within the Bet v 1-type conformation.
Conclusion: Our system allows the evaluation of patient-specific epitope profiles and will facilitate both the identification of clinically relevant epitopes as biomarkers and the monitoring of therapeutic outcomes to improve diagnosis, prognosis, and therapy of allergies caused by PR-10 proteins.
We introduce Implied Volatility Duration (IVD) as a new measure for the timing of uncertainty resolution, with a high IVD corresponding to late resolution. Portfolio sorts on a large cross-section of stocks indicate that investors demand on average about seven percent return per year as a compensation for a late resolution of uncertainty. In a general equilibrium model, we show that `late' stocks can only have higher expected returns than `early' stocks if the investor exhibits a preference for early resolution of uncertainty. Our empirical analysis thus provides a purely market-based assessment of the timing preferences of the marginal investor.
Relja, Borna ; Weber, Roxane ; Maraslioglu, Miriam ; Wagner, Nils ; Borsello, Tiziana ; Jobin, Christian ; Marzi, Ingo ; Lehnert, Mark
Background: Chronic ethanol (EtOH) abuse worsens pathophysiological derangements after hemorrhagic shock and resuscitation (H/R) that induce hepatic injury and strong inflammatory changes via JNK and NF-κB activation. Inhibiting JNK with a cell-penetrating, protease-resistant peptide D-JNKI-1 after H/R in mice with healthy livers ameliorated these effects. Here, we studied if JNK inhibition by D-JNKI-1 in chronically EtOH-fed mice after hemorrhagic shock prior to the onset of resuscitation also confers protection.
Methods: Male mice were fed a Lieber-DeCarli diet containing EtOH or an isocaloric control (ctrl) diet for 4 weeks. Animals were hemorrhaged for 90 min (32 ± 2 mm Hg) and randomly received either D-JNKI-1 (11 mg/kg, intraperitoneally, i. p.) or sterile saline as vehicle (veh) immediately before the onset of resuscitation. Sham animals underwent surgical procedures without H/R and were either D-JNKI-1 or veh treated. Two hours after resuscitation, blood samples and liver tissue were harvested.
Results: H/R induced hepatic injury with increased systemic interleukin (IL)-6 levels, and enhanced local gene expression of NF-κB-controlled genes such as intercellular adhesion molecule (ICAM)-1 and matrix metallopeptidase (MMP)9. c-Jun and NF-κB phosphorylation were increased after H/R. These effects were further increased in EtOH-fed mice after H/R. D-JNKI-1 application inhibited the proinflammatory changes and reduced significantly hepatic injury after H/R in ctrl-fed mice. Moreover, D-JNKI-1 reduces in ctrl-fed mice the H/R-induced c-Jun and NF-κB phosphorylation. However, in chronically EtOH-fed mice, JNK inhibition did not prevent the H/R-induced hepatic damage and proinflammatory changes nor c-Jun and NF-κB phosphorylation after H/R.
Conclusions: These results indicate, that JNK inhibition is protective only in not pre-harmed liver after H/R. In contrast, the pronounced H/R-induced liver damage in mice being chronically fed with ethanol cannot be prevented by JNK inhibition after H/R and seems to be under the control of NF-κB.
Caudillo-Plath, Lucía ; Rörup, Birte ; Heinritzi, Martin ; Marie, Guillaume ; Simon, Mario ; Wagner, Andrea C. ; Müller, Tatjana ; Granzin, Manuel ; Amorim, António ; Ataei, Farnoush ; Baalbaki, Rima ; Bertozzi, Barbara ; Brasseur, Zoé ; Chiu, Randall ; Chu, Biwu ; Dada, Lubna ; Duplissy, Jonathan ; Finkenzeller, Henning ; Gonzalez Carracedo, Loïc ; He, Xu-Cheng ; Hofbauer, Victoria ; Kong, Weimeng ; Lamkaddam, Houssni ; Lee, Chuan P. ; Lopez, Brandon ; Mahfouz, Naser G. A. ; Makhmutov, Vladimir ; Manninen, Hanna E. ; Marten, Ruby ; Massabò, Dario ; Mauldin, Roy L. ; Mentler, Bernhard ; Molteni, Ugo ; Onnela, Antti ; Pfeifer, Joschka ; Philippov, Maxim ; Piedehierro, Ana A. ; Schervish, Meredith ; Scholz, Wiebke ; Schulze, Benjamin ; Shen, Jiali ; Stolzenburg, Dominik ; Stožkov, Ju. I. ; Surdu, Mihnea ; Tauber, Christian ; Tham, Yee Jun ; Tian, Ping ; Tomé, António ; Vogt, Steffen ; Wang, Mingyi ; Wang, Dongyu S. ; Weber, Stefan K. ; Welti, André ; Yonghong, Wang ; Yusheng, Wu ; Zauner-Wieczorek, Marcel ; Baltensperger, Urs ; El Haddad, Imad ; Flagan, Richard C. ; Hansel, Armin ; Höhler, Kristina ; Kirkby, Jasper ; Kulmala, Markku ; Lehtipalo, Katrianne ; Möhler, Ottmar ; Saathoff, Harald ; Volkamer, Rainer ; Winkler, Paul M. ; Donahue, Neil M. ; Kürten, Christoph Andreas ; Curtius, Joachim
Biogenic organic precursors play an important role in atmospheric new particle formation (NPF). One of the major precursor species is α-pinene, which upon oxidation can form a suite of products covering a wide range of volatilities. Highly oxygenated organic molecules (HOMs) comprise a fraction of the oxidation products formed. While it is known that HOMs contribute to secondary organic aerosol (SOA) formation, including NPF, they have not been well studied in newly formed particles due to their very low mass concentrations. Here we present gas- and particle-phase chemical composition data from experimental studies of α-pinene oxidation, including in the presence of isoprene, at temperatures (−50 and −30 ∘C) and relative humidities (20 % and 60 %) relevant in the upper free troposphere. The measurements took place at the CERN Cosmics Leaving Outdoor Droplets (CLOUD) chamber. The particle chemical composition was analyzed by a thermal desorption differential mobility analyzer (TD-DMA) coupled to a nitrate chemical ionization–atmospheric pressure interface–time-of-flight (CI-APi-TOF) mass spectrometer. CI-APi-TOF was used for particle- and gas-phase measurements, applying the same ionization and detection scheme. Our measurements revealed the presence of C8−10 monomers and C18−20 dimers as the major compounds in the particles (diameter up to ∼ 100 nm). Particularly, for the system with isoprene added, C5 (C5H10O5−7) and C15 compounds (C15H24O5−10) were detected. This observation is consistent with the previously observed formation of such compounds in the gas phase. However, although the C5 and C15 compounds do not easily nucleate, our measurements indicate that they can still contribute to the particle growth at free tropospheric conditions. For the experiments reported here, most likely isoprene oxidation products enhance the growth of particles larger than 15 nm. Additionally, we report on the nucleation rates measured at 1.7 nm (J1.7 nm) and compared with previous studies, we found lower J1.7 nm values, very likely due to the higher α-pinene and ozone mixing ratios used in the present study.
Caudillo-Plath, Lucı́a ; Rörup, Birte ; Heinritzi, Martin ; Marie, Guillaume ; Simon, Mario ; Wagner, Andrea C. ; Müller, Tatjana ; Granzin, Manuel ; Amorim, Antonio ; Ataei, Farnoush ; Baalbaki, Rima ; Bertozzi, Barbara ; Brasseur, Zoé ; Chiu, Randall ; Chu, Biwu ; Dada, Lubna ; Duplissy, Jonathan ; Finkenzeller, Henning ; Gonzalez Carracedo, Loïc ; He, Xu-Cheng ; Hofbauer, Victoria ; Kong, Weimeng ; Lamkaddam, Houssni ; Lee, Chuan P ; Lopez, Brandon ; Mahfouz, Naser G. A. ; Makhmutov, Vladimir ; Manninen, Hanna E. ; Marten, Ruby ; Massabò, Dario ; Mauldin, Roy L. ; Mentler, Bernhard ; Molteni, Ugo ; Onnela, Antti ; Pfeifer, Joschka ; Philippov, Maxim ; Piedehierro, Ana A. ; Schervish, Meredith ; Scholz, Wiebke ; Schulze, Benjamin ; Shen, Jiali ; Stolzenburg, Dominik ; Stožkov, Ju. I. ; Surdu, Mihnea ; Tauber, Christian ; Tham, Yee Jun ; Tian, Ping ; Tomé, António ; Vogt, Steffen ; Wang, Mingyi ; Wang, Dongyu S. ; Weber, Stefan K. ; Welti, André ; Yonghong, Wang ; Yusheng, Wu ; Zauner-Wieczorek, Marcel ; Baltensperger, Urs ; El Haddad, Imad ; Flagan, Richard C. ; Hansel, Armin ; Höhler, Kristina ; Kirkby, Jasper ; Kulmala, Markku ; Lehtipalo, Katrianne ; Möhler, Ottmar ; Saathoff, Harald ; Volkamer, Rainer ; Winkler, Paul M. ; Donahue, Neil M. ; Kürten, Christoph Andreas ; Curtius, Joachim
Biogenic organic precursors play an important role in atmospheric new particle formation (NPF). One of the major precursor species is α-pinene, which upon oxidation can form a suite of products covering a wide range of volatilities. Highly oxygenated organic molecules (HOMs) comprise a fraction of the oxidation products formed. While it is known that HOMs contribute to secondary organic aerosol (SOA) formation, including NPF, they have not been well studied in newly formed particles due to their very low mass concentrations. Here we present gas- and particle-phase chemical composition data from experimental studies of α-pinene oxidation, including in the presence of isoprene, at temperatures (−50 and −30 ∘C) and relative humidities (20 % and 60 %) relevant in the upper free troposphere. The measurements took place at the CERN Cosmics Leaving Outdoor Droplets (CLOUD) chamber. The particle chemical composition was analyzed by a thermal desorption differential mobility analyzer (TD-DMA) coupled to a nitrate chemical ionization–atmospheric pressure interface–time-of-flight (CI-APi-TOF) mass spectrometer. CI-APi-TOF was used for particle- and gas-phase measurements, applying the same ionization and detection scheme. Our measurements revealed the presence of C8−10 monomers and C18−20 dimers as the major compounds in the particles (diameter up to ∼ 100 nm). Particularly, for the system with isoprene added, C5 (C5H10O5−7) and C15 compounds (C15H24O5−10) were detected. This observation is consistent with the previously observed formation of such compounds in the gas phase. However, although the C5 and C15 compounds do not easily nucleate, our measurements indicate that they can still contribute to the particle growth at free tropospheric conditions. For the experiments reported here, most likely isoprene oxidation products enhance the growth of particles larger than 15 nm. Additionally, we report on the nucleation rates measured at 1.7 nm (J1.7 nm) and compared with previous studies, we found lower J1.7 nm values, very likely due to the higher α-pinene and ozone mixing ratios used in the present study.
Clees, Ada-Sophia ; Stolp, Verena ; Häupl, Björn ; Fuhrmann, Dominik Christian ; Wempe, Frank ; Seibert, Marcel ; Weber, Sarah ; Banning, Antje ; Tikkanen, Ritva ; Williams, Richard ; Brüne, Bernhard ; Serve, Hubert ; Schnütgen, Frank ; Metzler, Ivana von ; Kurrle, Nina Susanne
Multiple myeloma (MM) is the second most common hematologic malignancy, which is characterized by clonal proliferation of neoplastic plasma cells in the bone marrow. This microenvironment is characterized by low oxygen levels (1–6% O2), known as hypoxia. For MM cells, hypoxia is a physiologic feature that has been described to promote an aggressive phenotype and to confer drug resistance. However, studies on hypoxia are scarce and show little conformity. Here, we analyzed the mRNA expression of previously determined hypoxia markers to define the temporal adaptation of MM cells to chronic hypoxia. Subsequent analyses of the global proteome in MM cells and the stromal cell line HS-5 revealed hypoxia-dependent regulation of proteins, which directly or indirectly upregulate glycolysis. In addition, chronic hypoxia led to MM-specific regulation of nine distinct proteins. One of these proteins is the cysteine protease legumain (LGMN), the depletion of which led to a significant growth disadvantage of MM cell lines that is enhanced under hypoxia. Thus, herein, we report a methodologic strategy to examine MM cells under physiologic hypoxic conditions in vitro and to decipher and study previously masked hypoxia-specific therapeutic targets such as the cysteine protease LGMN.
Bartsch, Detlef K. ; Dotzenrath, Cornelia ; Vorländer, Christian ; Zielke, Andreas ; Weber, Theresia ; Buhr, Heinz J. ; Klinger, Carsten ; Lorenz, Kerstin
Background: To evaluate the current indications, resection strategies and short-term outcomes of surgery for benign goitre in a country with endemic goitre. Methods: Data of patients who underwent surgery for benign goitre were retrieved from the prospective StuDoQ/Thyroid registry and retrospectively analysed regarding the patient’s demographics, indications for surgery, surgical procedures, histology, and perioperative outcomes. Results: In a 15-month period, 12,888 patients from 83 departments underwent thyroid resections for benign conditions. Main indications for surgery were exclusion of malignancy (68%), compression symptoms (20.7%) and hyperthyroidism (9.7%). Preoperative fine needle aspiration cytology was performed in only 12.2% of patients with the indication "exclusion of malignancy". Thyroidectomy (49.8%) or hemithyroidectomy (36.9%) were performed in 86.7% of patients. Minimally invasive or alternative surgical techniques were applied in only 2.2%. Intraoperative neuromonitoring was used in 98.4% of procedures, in 97.5% of patients at least one parathyroid gland was visualized, and in 15.3% of patients parathyroid tissue was autografted, respectively. The rates of unilateral and bilateral transient recurrent nerve palsy were 3.6% and 0.07% of nerves at risk, the rate of transitory hypoparathyroidism was 15.3%. The rates of postoperative bleeding and wound infections requiring reoperation were 1.4% and 0.07%, respectively. Conclusions: The indication "exclusion of malignancy" is made too liberally, and there is a strong attitude to perform complete thyroid resections. Postoperative hypoparathyroidism is the major complication after surgery for benign thyroid disease, thus requiring more awareness.
Ney, Julia ; Hoffmann, Katleen ; Meybohm, Patrick ; Goetzenich, Andreas ; Kraemer, Sandra ; Benstöm, Carina ; Weber, Nina C. ; Bickenbach, Johannes ; Rossaint, Rolf ; Marx, Gernot ; Zacharowski, Kai ; Bernhagen, Jürgen ; Stoppe, Christian
In contrast to several smaller studies, which demonstrate that remote ischemic preconditioning (RIPC) reduces myocardial injury in patients that undergo cardiovascular surgery, the RIPHeart study failed to demonstrate beneficial effects of troponin release and clinical outcome in propofol-anesthetized cardiac surgery patients. Therefore, we addressed the potential biochemical mechanisms triggered by RIPC. This is a predefined prospective sub-analysis of the randomized and controlled RIPHeart study in cardiac surgery patients (n = 40) that was recently published. Blood samples were drawn from patients prior to surgery, after RIPC of four cycles of 5 min arm ischemia/5 min reperfusion (n = 19) and the sham (n = 21) procedure, after connection to cardiopulmonary bypass (CPB), at the end of surgery, 24 h postoperatively, and 48 h postoperatively for the measurement of troponin T, macrophage migration inhibitory factor (MIF), stromal cell-derived factor 1 (CXCL12), IL-6, CXCL8, and IL-10. After RIPC, right atrial tissue samples were taken for the measurement of extracellular-signal regulated kinase (ERK1/2), protein kinase B (AKT), Glycogen synthase kinase 3 (GSK-3β), protein kinase C (PKCε), and MIF content. RIPC did not significantly reduce the troponin release when compared with the sham procedure. MIF serum levels intraoperatively increased, peaking at intensive care unit (ICU) admission (with an increase of 48.04%, p = 0.164 in RIPC; and 69.64%, p = 0.023 over the baseline in the sham procedure), and decreased back to the baseline 24 h after surgery, with no differences between the groups. In the right atrial tissue, MIF content decreased after RIPC (1.040 ± 1.032 Arbitrary units [au] in RIPC vs. 2.028 ± 1.631 [au] in the sham procedure, p < 0.05). CXCL12 serum levels increased significantly over the baseline at the end of surgery, with no differences between the groups. ERK1/2, AKT, GSK-3β, and PKCɛ phosphorylation in the right atrial samples were no different between the groups. No difference was found in IL-6, CXCL8, and IL10 serum levels between the groups. In this cohort of cardiac surgery patients that received propofol anesthesia, we could not show a release of potential mediators of signaling, nor an effect on the inflammatory response, nor an activation of well-established protein kinases after RIPC. Based on these data, we cannot exclude that confounding factors, such as propofol, may have interfered with RIPC.
DIGITAL CURRENCIES ARE A GLOBALLY SPREADING PHENOMENON THAT IS FREQUENTLY AND PROMINENTLY ADDRESSED BY MEDIA, POLITICS AND ACADEMIA. WE AIM AT GIVING EMPIRICAL INSIGHTS ON WHETHER USERS’ INTEREST REGARDING DIGITAL CURRENCIES IS DRIVEN BY ITS APPEAL AS AN ASSET OR ITS UTILITY AS A CURRENCY. BASED ON OUR EVALUATION, WE FIND STRONG INDICATIONS THAT ESPECIALLY UNINFORMED USERS APPROACHING BITCOIN ARE NOT PRIMARILY INTERESTED IN AN ALTERNATIVE TRANSACTION SYSTEM, BUT SEEK TO PARTICIPATE IN AN ALTERNATIVE INVESTMENT VEHICLE.
The ubiquitous detection of microplastics in aquatic ecosystems promotes the concern for adverse impacts on freshwater ecosystems. The wide variety of material types, sizes, shapes, and physicochemical properties renders interactions with biota via multiple pathways probable.
So far, our knowledge about the uptake and biological effects of microplastics comes from laboratory studies, applying simplified exposure regimes (e.g., one polymer and size, spherical shape, high concentrations) often with limited environmental relevance. However, the available data illustrates species- and material-related interactions and highlights that microplastics represent a multifaceted stressor. Particle-related toxicities will be driven by polymer type, size, and shape. Chemical toxicity is driven by the adsorption-desorption kinetics of additives and pollutants. In addition, microbial colonization, the formation of hetero-aggregates, and the evolutionary adaptations of the biological receptor further increase the complexity of microplastics as stressors. Therefore, the aim of this chapter is to synthesize and critically revisit these aspects based on the state of the science in freshwater research. Where unavailable we supplement this with data on marine biota. This provides an insight into the direction of future research.
In this regard, the challenge is to understand the complex interactions of biota and plastic materials and to identify the toxicologically most relevant characteristics of the plethora of microplastics. Importantly, as the direct biological impacts of natural particles may be similar, future research needs to benchmark synthetic against natural materials. Finally, given the scale of the research question, we need a multidisciplinary approach to understand the role of microplastics in a multiple-particle world.
Gaubatz, Jennifer ; Ernst, Leon ; Prillwitz, Conrad ; David, Bastian ; Lüchters, Guido ; Schramm, Johannes ; Weber, Bernd ; Surges, Rainer ; Hattingen, Elke ; Schlaug, Gottfried ; Elger, Christian Erich ; Rüber, Theodor
Motor function after hemispheric lesions has been associated with the structural integrity of either the pyramidal tract (PT) or alternate motor fibers (aMF). In this study, we aimed to differentially characterize the roles of PT and aMF in motor compensation by relating diffusion-tensor-imaging-derived parameters of white matter microstructure to measures of proximal and distal motor function in patients after hemispherotomy. Twenty-five patients (13 women; mean age: 21.1 years) after hemispherotomy (at mean age: 12.4 years) underwent Diffusion Tensor Imaging and evaluation of motor function using the Fugl-Meyer Assessment and the index finger tapping test. Regression analyses revealed that fractional anisotropy of the PT explained (p = 0.050) distal motor function including finger tapping rate (p = 0.027), whereas fractional anisotropy of aMF originating in the contralesional cortex and crossing to the ipsilesional hemisphere in the pons explained proximal motor function (p = 0.001). Age at surgery was found to be the only clinical variable to explain motor function (p < 0.001). Our results are indicative of complementary roles of the PT and of aMF in motor compensation of hemispherotomy mediating distal and proximal motor compensation of the upper limb, respectively.
Bauer, Tobias ; Ernst, Leon ; David, Bastian ; Becker, Albert J. ; Wagner, Jan ; Witt, Juri-Alexander ; Helmstaedter, Christoph ; Weber, Bernd ; Hattingen, Elke ; Elger, Christian Erich ; Surges, Rainer ; Rüber, Theodor
Limbic encephalitis (LE) is an autoimmune syndrome often associated with temporal lobe epilepsy. Recent research suggests that particular structural changes in LE depend on the type of the associated antibody and occur in both mesiotemporal gray matter and white matter regions. However, it remains questionable to what degree conventional diffusion tensor imaging (DTI)-methods reflect alterations in white matter microstructure, since these methods do not account for crossing fibers. To address this methodological shortcoming, we applied fixel-based analysis as a novel technique modeling distinct fiber populations. For our study, 19 patients with LE associated with autoantibodies against glutamic acid decarboxylase 65 (GAD-LE, mean age = 35.9 years, 11 females), 4 patients with LE associated with autoantibodies against leucine-rich glioma-inactivated 1 (LGI1-LE, mean age = 63.3 years, 2 females), 5 patients with LE associated with contactin-associated protein-like 2 (CASPR2, mean age = 57.4, 0 females), 20 age- and gender-matched control patients with hippocampal sclerosis (19 GAD-LE control patients: mean age = 35.1 years, 11 females; 4 LGI1-LE control patients: mean age = 52.6 years, 2 females; 5 CASPR2-LE control patients: mean age = 42.7 years, 0 females; 10 patients are included in more than one group) and 33 age- and gender-matched healthy control subjects (19 GAD-LE healthy controls: mean age = 34.6 years, 11 females; 8 LGI1-LE healthy controls: mean age = 57.0 years, 4 females, 10 CASPR2-LE healthy controls: mean age = 57.2 years, 0 females; 4 subjects are included in more than one group) underwent structural imaging and DTI at 3 T and neuropsychological testing. Patient images were oriented according to lateralization in EEG resulting in an affected and unaffected hemisphere. Fixel-based metrics fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC = FD · FC) were calculated to retrieve information about white matter integrity both on the micro- and the macroscale. As compared to healthy controls, patients with GAD-LE showed significantly (family-wise error-corrected, p < 0.05) lower FDC in the superior longitudinal fascicle bilaterally and in the isthmus of the corpus callosum. In CASPR2-LE, lower FDC in the superior longitudinal fascicle was only present in the affected hemisphere. In LGI1-LE, we did not find any white matter alteration of the superior longitudinal fascicle. In an explorative tract-based correlation analysis within the GAD-LE group, only a correlation between the left/right ratio of FC values of the superior longitudinal fascicle and verbal memory performance (R = 0.64, Holm-Bonferroni corrected p < 0.048) remained significant after correcting for multiple comparisons. Our results underscore the concept of LE as a disease comprising a broad and heterogeneous group of entities and contribute novel aspects to the pathomechanistic understanding of this disease that may strengthen the role of MRI in the diagnosis of LE.