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On the observation of mesospheric air inside the arctic stratospheric polar vortex in early 2003
(2005)
Engel, Andreas ; Möbius, Tanja ; Haase, Hans-Peter ; Bönisch, Harald ; Wetter, Thomas ; Schmidt, Ulrich ; Levin, Ingeborg ; Reddmann, Thomas ; Oelhaf, Hermann ; Wetzel, Gerald ; Grunow, Katja ; Huret, Nathalie ; Pirre, Michel
During several balloon flights inside the Arctic polar vortex in early 2003, unusual trace gas distributions were observed, which indicate a strong influence of mesospheric air in the stratosphere. The tuneable diode laser (TDL) instrument SPIRALE (Spectroscopie InFrarouge par Absorption de Lasers Embarqués) measured unusually high CO values (up to 600 ppb) on 27 January at about 30 km altitude. The cryosampler BONBON sampled air masses with very high molecular Hydrogen, extremely low SF6 and enhanced CO values on 6 March at about 25 km altitude. Finally, the MIPAS (Michelson Interferometer for Passive Atmospheric Sounding) Fourier Transform Infra-Red (FTIR) spectrometer showed NOy values which are significantly higher than NOy* (the NOy derived from a correlation between N2O and NOy under undisturbed conditions), on 21 and 22 March in a layer centred at 22 km altitude. Thus, the mesospheric air seems to have been present in a layer descending from about 30 km in late January to 25 km altitude in early March and about 22 km altitude on 20 March. We present corroborating evidence from a model study using the KASIMA (KArlsruhe Simulation model of the Middle Atmosphere) model that also shows a layer of mesospheric air, which descended into the stratosphere in November and early December 2002, before the minor warming which occurred in late December 2002 lead to a descent of upper stratospheric air, cutting of a layer in which mesospheric air is present. This layer then descended inside the vortex over the course of the winter. The same feature is found in trajectory calculations, based on a large number of trajectories started in the vicinity of the observations on 6 March. Based on the difference between the mean age derived from SF6 (which has an irreversible mesospheric loss) and from CO2 (whose mesospheric loss is much smaller and reversible) we estimate that the fraction of mesospheric air in the layer observed on 6 March, must have been somewhere between 35% and 100%.
Leistenschneider, Armin ; Aumann, Thomas ; Boretzky, Konstanze ; Canto, Luiz Felipe ; Carlson, Brett Vern ; Cortina, Dolores ; Datta Pramanik, Ushasi ; Elze, Thomas W. ; Emling, Hans ; Geissel, Hans ; Grünschloss, Alexander ; Helariutta, Kerttuli ; Hellström, Margareta ; Hussein, Mahir S. ; Ilievski, Stamenko ; Kratz, Jens-Volker ; Kulessa, Reinhard ; Khiem, Le Hong ; Lubkiewicz, Edvard ; Münzenberg, Gottfried ; Palit, Rudrayoti ; Reiter, Peter ; Scheidenberger, Christoph ; Schmidt, Karl-Heinz ; Simon, Haik ; Sümmerer, Klaus ; Wajda, Eugeniusz ; Walús, Wladek
Abrasion-ablation models and the empirical EPAX parametrization of projectile fragmentation are described. Their cross section predictions are compared to recent data of the fragmentation of secondary beams of neutron-rich, unstable 19,20,21O isotopes at beam energies near 600 MeV/nucleon as well as data for stable 17,18O beams.
Bücherschau
(2004)
Engel, Andreas ; Möbius, Tanja ; Haase, Hans-Peter ; Bönisch, Harald ; Wetter, Thomas ; Schmidt, Ulrich ; Levin, Ingeborg ; Reddmann, Thomas ; Oelhaf, Hermann ; Wetzel, Gerald ; Grunow, Katja ; Huret, Nathalie ; Pirre, Michel
During several balloon flights inside the Arctic polar vortex in early 2003, unusual trace gas distributions were observed, which indicate a strong influence of mesospheric air in the stratosphere. The tuneable diode laser (TDL) instrument SPIRALE (Spectroscopie InFrarouge par Absorption de Lasers Embarqués) measured unusually high CO values (up to 600 ppb) on 27 January at about 30 km altitude. The cryosampler BONBON sampled air masses with very high molecular Hydrogen, extremely low SF6 and enhanced CO values on 6 March at about 25 km altitude. Finally, the MIPAS (Michelson Interferometer for Passive Atmospheric Sounding) Fourier Transform Infra-Red (FTIR) spectrometer showed NOy values which are significantly higher than NOy* (the NOy derived from a correlation between N2O and NOy under undisturbed conditions), on 21 and 22 March in a layer centred at 22 km altitude. Thus, the mesospheric air seems to have been present in a layer descending from about 30 km in late January to 25 km altitude in early March and about 22 km altitude on 20 March. We present corroborating evidence from a model study using the KASIMA (KArlsruhe Simulation model of the Middle Atmosphere) model that also shows a layer of mesospheric air, which descended into the stratosphere in November and early December 2002, before the minor warming which occurred in late December 2002 lead to a descent of upper stratospheric air, cutting of a layer in which mesospheric air is present. This layer then descended inside the vortex over the course of the winter. The same feature is found in trajectory calculations, based on a large number of trajectories started in the vicinity of the observations on 6 March. Based on the difference between the mean age derived from SF6 (which has an irreversible mesospheric loss) and from CO2 (whose mesospheric loss is much smaller and reversible) we estimate that the fraction of mesospheric air in the layer observed on 6 March, must have been somewhere between 35% and 100%.
Beck, Michael ; Hartwich, Julius ; Eckstein, Markus ; Schmidt, Daniela ; Gostian, Antoniu-Oreste ; Müller, Sarina ; Rutzner, Sandra ; Gaipl, Udo Sebastian ; Müller-von der Grün, Jens ; Illmer, Thomas ; Hautmann, Matthias Günther ; Klautke, Gunther ; Döscher, Johannes ; Brunner, Thomas B. ; Tamaskovics, Bálint ; Hartmann, Arndt ; Iro, Heinrich ; Kuwert, Torsten ; Fietkau, Rainer ; Hecht, Markus ; Semrau, Sabine
Aim: In the CheckRad-CD8 trial patients with locally advanced head and neck squamous cell cancer are treated with a single cycle of induction chemo-immunotherapy (ICIT). Patients with pathological complete response (pCR) in the re-biopsy enter radioimmunotherapy. Our goal was to study the value of F-18-FDG PET/CT in the prediction of pCR after induction therapy.
Methods: Patients treated within the CheckRad-CD8 trial that additionally received FDG- PET/CT imaging at the following two time points were included: 3–14 days before (pre-ICIT) and 21–28 days after (post-ICIT) receiving ICIT. Tracer uptake in primary tumors (PT) and suspicious cervical lymph nodes (LN +) was measured using different quantitative parameters on EANM Research Ltd (EARL) accredited PET reconstructions. In addition, mean FDG uptake levels in lymphatic and hematopoietic organs were examined. Percent decrease (Δ) in FDG uptake was calculated for all parameters. Biopsy of the PT post-ICIT acquired after FDG-PET/CT served as reference. The cohort was divided in patients with pCR and residual tumor (ReTu).
Results: Thirty-one patients were included. In ROC analysis, ΔSUVmax PT performed best (AUC = 0.89) in predicting pCR (n = 17), with a decline of at least 60% (sensitivity, 0.77; specificity, 0.93). Residual SUVmax PT post-ICIT performed best in predicting ReTu (n = 14), at a cutpoint of 6.0 (AUC = 0.91; sensitivity, 0.86; specificity, 0.88). Combining two quantitative parameters (ΔSUVmax ≥ 50% and SUVmax PT post-ICIT ≤ 6.0) conferred a sensitivity of 0.81 and a specificity of 0.93 for determining pCR. Background activity in lymphatic organs or uptake in suspected cervical lymph node metastases lacked significant predictive value.
Conclusion: FDG-PET/CT can identify patients with pCR after ICIT via residual FDG uptake levels in primary tumors and the related changes compared to baseline. FDG-uptake in LN + had no predictive value.
Trial registry: ClinicalTrials.gov identifier: NCT03426657.
Slik, J. W. Ferry ; Franklin, Janet ; Arroyo-Rodríguez, Víctor ; Field, Richard ; Aguilar, Salomon ; Aguirre, Nikolay ; Ahumada, Jorge ; Aiba, Shin-Ichiro ; Alves, Luciana F. ; Anitha, Kamalakumari ; Avella, Andres ; Mora, Francisco ; Aymard, Gerardo A. ; Báez, Selene ; Balvanera, Patricia ; Bastian, Meredith L. ; Bastin, Jean-François ; Bellingham, Peter ; van den Berg, Eduardo ; da Conceição Bispo, Polyanna ; Boeckx, Pascal ; Böhning-Gaese, Katrin ; Bongers, Frans ; Boyle, Brad ; Brambach, Fabian ; Brearley, Francis Q. ; Brown, Sandra ; Chai, Shauna-Lee ; Chazdon, Robin L. ; Chen, Shengbin ; Chhang, Phourin ; Chuyong, George ; Ewangog, Corneille ; Coronado, Indiana ; Cristóbal-Azkarate, Jurgi ; Culmsee, Heike ; Damas, Kipiro ; Dattaraja, Handanakere Shivaramaiah ; Davidar, Priya ; DeWalt, Saara J. ; Din, Hazimah ; Drake, Donald R. ; Duque, Alvaro ; Durigan, Giselda ; Eichhorn, Karl ; Schmidt Eler, Eduardo ; Enoki, Tsutomu ; Ensslin, Andreas ; Fandohan, Adandé Belarmain ; Farwig, Nina ; Feeley, Kenneth J. ; Fischer, Markus ; Forshed, Olle ; Garcia, Queila Souza ; Garkoti, Satish Chandra ; Gillespie, Thomas William ; Gillet, Jean-Francois ; Gonmadje, Christelle ; Granzow-de la Cerda, Iñigo ; Griffith, Daniel M. ; Grogan, James ; Hakeem, Khalid Rehman ; Harris, David J. ; Harrison, Rhett D. ; Hector, Andy ; Hemp, Andreas ; Homeier, Jürgen ; Hussain, M. Shah ; Ibarra Manríquez, Guillermo ; Hanum, I. Faridah ; Imai, Nobuo ; Jansen, Patrick A. ; Joly, Carlos Alfredo ; Joseph, Shijo ; Kartawinata, Kuswata ; Kearsley, Elizabeth ; Kelly, Daniel L. ; Kessler, Michael ; Killeen, Timothy J. ; Kooyman, Robert ; Laumonier, Yves ; Laurance, Susan G. ; Laurance, William F. ; Lawes, Michael J. ; Letcher, Susan G. ; Lindsell, Jeremy ; Lovett, Jon ; Lozada, Jose ; Lu, Xinghui ; Lykke, Anne Mette ; Bin Mahmud, Khairil ; Mahayani, Ni Putu Diana ; Mansor, Asyraf ; Marshall, Andrew R. ; Martin, Emanuel H. ; Leal Matos, Darley Calderado ; Meave, Jorge A. ; Melo, Felipe P. L. ; Aguirre Mendoza, Zhofre ; Metali, Faizah ; Medjibe, Vincent P. ; Metzger, Jean Paul ; Metzker, Thiago ; Mohandass, Dharmalingam ; Munguía-Rosas, Miguel A. ; Muñoz, Rodrigo ; Nurtjahy, Eddy ; Lenza de Oliveira, Eddie ; Onrizal, Onrizal ; Parolin, Pia ; Parren, Marc ; Parthasarathy, Narayanaswamy ; Paudel, Ekananda ; Perez, Rolando ; Pérez-García, Eduardo A. ; Pommer, Ulf ; Poorter, Lourens ; Qi, Lan ; F. Piedade, Maria Teresa ; Rodrigues Pinto, José Roberto ; Dalberg Poulsen, Axel ; Poulsen, John R. ; Powers, Jennifer S. ; Prasad, Rama Chandra ; Puyravaud, Jean-Philippe ; Rangel, Orlando ; Reitsma, Jan ; S. B. Rocha, Diogo ; Rolim, Samir ; Rovero, Francesco ; Rozak, Andes ; Ruokolainen, Kalle ; Rutishauser, Ervan ; Rutten, Gemma ; Mohd. Said, Mohd. Nizam ; Saiter, Felipe Z. ; Saner, Philippe ; Santos, Braulio ; dos Santos, João Roberto ; Sarker, Swapan Kumar ; Schmitt, Christine B. ; Schöngart, Jochen ; Schulze, Mark ; Sheil, Douglas ; Sist, Plinio ; Souza, Alexandre F. ; Spironello, Wilson Roberto ; Sposito, Tereza ; Steinmetz, Robert ; Stevart, Tariq ; Suganuma, Marcio Seiji ; Sukri, Rahayu ; Sultana, Aisha ; Sukumar, Raman ; Sunderland, Terry ; Supriyadi, Agus ; Suresh, Hebbalalu S. ; Suzuki, Eizi ; Tabarelli, Marcelo ; Tang, Jianwei ; Tanner, Edmund V. J. ; Targhetta, Natalia ; Theilade, Ida ; Thomas, Duncan ; Timberlake, Jonathan ; de Morisson Valeriano, Márcio ; Valkenburg, Johan van ; Do, Tran Van ; Sam, Hoang Van ; Vandermeer, John H. ; Verbeeck, Hans ; Vetaas, Ole Reidar ; Adekunle, Victor ; Vieira, Simone A. ; Webb, Campbell O. ; Webb, Edward L. ; Whitfeld, Timothy ; Wich, Serge ; Williams, John ; Wiser, Susan ; Wittmann, Florian ; Yang, Xiaobo ; Adou Yao, C. Yves ; Yap, Sandra L. ; Zahawie, Rakan A. ; Zakaria, Rahmad ; Zang, Runguo
Knowledge about the biogeographic affinities of the world’s tropical forests helps to better understand regional differences in forest structure, diversity, composition, and dynamics. Such understanding will enable anticipation of region-specific responses to global environmental change. Modern phylogenies, in combination with broad coverage of species inventory data, now allow for global biogeographic analyses that take species evolutionary distance into account. Here we present a classification of the world’s tropical forests based on their phylogenetic similarity. We identify five principal floristic regions and their floristic relationships: (i) Indo-Pacific, (ii) Subtropical, (iii) African, (iv) American, and (v) Dry forests. Our results do not support the traditional neo- versus paleotropical forest division but instead separate the combined American and African forests from their Indo-Pacific counterparts. We also find indications for the existence of a global dry forest region, with representatives in America, Africa, Madagascar, and India. Additionally, a northern-hemisphere Subtropical forest region was identified with representatives in Asia and America, providing support for a link between Asian and American northern-hemisphere forests.
Borsch, Thomas ; Stevens, Albert-Dieter ; Häffner, Eva ; Güntsch, Anton ; Berendsohn, Walter G. ; Appelhans, Marc Sebastian ; Barilaro, Christina ; Beszteri, Bánk ; Blattner, Frank R. ; Bossdorf, Oliver ; Dalitz, Helmut ; Dressler, Stefan ; Duque-Thüs, Rhinaixa ; Esser, Hans-Joachim ; Franzke, Andreas ; Goetze, Dethardt ; Grein, Michaela ; Grünert, Uta ; Hellwig, Frank ; Hentschel, Jörn ; Hörandl, Elvira ; Janßen, Thomas ; Jürgens, Norbert ; Kadereit, Gudrun ; Karisch, Timm ; Koch, Marcus ; Müller, Frank ; Müller, Jochen ; Ober, Dietrich ; Porembski, Stefan ; Poschlod, Peter ; Printzen, Christian ; Röser, Martin ; Sack, Peter ; Schlüter, Philipp M. ; Schmidt, Marco ; Schnittler, Martin ; Scholler, Markus ; Schultz, Matthias ; Seeber, Elke ; Simmel, Josef ; Stiller, Michael ; Thiv, Mike ; Thüs, Holger ; Tkach, Natalia ; Triebel, Dagmar ; Warnke, Ursula ; Weibulat, Tanja ; Wesche, Karsten ; Yurkov, Andrey ; Zizka, Georg
Plants, fungi and algae are important components of global biodiversity and are fundamental to all ecosystems. They are the basis for human well-being, providing food, materials and medicines. Specimens of all three groups of organisms are accommodated in herbaria, where they are commonly referred to as botanical specimens.The large number of specimens in herbaria provides an ample, permanent and continuously improving knowledge base on these organisms and an indispensable source for the analysis of the distribution of species in space and time critical for current and future research relating to global biodiversity. In order to make full use of this resource, a research infrastructure has to be built that grants comprehensive and free access to the information in herbaria and botanical collections in general. This can be achieved through digitization of the botanical objects and associated data.The botanical research community can count on a long-standing tradition of collaboration among institutions and individuals. It agreed on data standards and standard services even before the advent of computerization and information networking, an example being the Index Herbariorum as a global registry of herbaria helping towards the unique identification of specimens cited in the literature.In the spirit of this collaborative history, 51 representatives from 30 institutions advocate to start the digitization of botanical collections with the overall wall-to-wall digitization of the flat objects stored in German herbaria. Germany has 70 herbaria holding almost 23 million specimens according to a national survey carried out in 2019. 87% of these specimens are not yet digitized. Experiences from other countries like France, the Netherlands, Finland, the US and Australia show that herbaria can be comprehensively and cost-efficiently digitized in a relatively short time due to established workflows and protocols for the high-throughput digitization of flat objects.Most of the herbaria are part of a university (34), fewer belong to municipal museums (10) or state museums (8), six herbaria belong to institutions also supported by federal funds such as Leibniz institutes, and four belong to non-governmental organizations. A common data infrastructure must therefore integrate different kinds of institutions.Making full use of the data gained by digitization requires the set-up of a digital infrastructure for storage, archiving, content indexing and networking as well as standardized access for the scientific use of digital objects. A standards-based portfolio of technical components has already been developed and successfully tested by the Biodiversity Informatics Community over the last two decades, comprising among others access protocols, collection databases, portals, tools for semantic enrichment and annotation, international networking, storage and archiving in accordance with international standards. This was achieved through the funding by national and international programs and initiatives, which also paved the road for the German contribution to the Global Biodiversity Information Facility (GBIF).Herbaria constitute a large part of the German botanical collections that also comprise living collections in botanical gardens and seed banks, DNA- and tissue samples, specimens preserved in fluids or on microscope slides and more. Once the herbaria are digitized, these resources can be integrated, adding to the value of the overall research infrastructure. The community has agreed on tasks that are shared between the herbaria, as the German GBIF model already successfully demonstrates.We have compiled nine scientific use cases of immediate societal relevance for an integrated infrastructure of botanical collections. They address accelerated biodiversity discovery and research, biomonitoring and conservation planning, biodiversity modelling, the generation of trait information, automated image recognition by artificial intelligence, automated pathogen detection, contextualization by interlinking objects, enabling provenance research, as well as education, outreach and citizen science.We propose to start this initiative now in order to valorize German botanical collections as a vital part of a worldwide biodiversity data pool.
In diesem Aufsatz geht es um die Datenbank ‚Mehrsprachigkeit’ und das System EXMARaLDA, die am SFB 538 ‚Mehrsprachigkeit’ der Universität Hamburg entwickelt werden. Da deren konzeptuelle und technische Details bereits an anderer Stelle ausführlich dargestellt worden sind (z.B. Schmidt 2004), soll der Schwerpunkt hier einerseits auf solchen Aspekten liegen, die – gemäß dem Thema des Workshops – mit allgemeineren Fragen zum Umgang mit computerverwertbaren, heterogenen linguistischen Datenbeständen zu tun haben. Andererseits soll versucht werden, aus den praktischen Erfahrungen der nunmehr vierjährigen Projektarbeit einige Erkenntnisse abzuleiten, die über den konkreten Projektzusammenhang hinaus für die weitere Arbeit auf diesem Gebiet interessant sein könnten.
Gibt es eine moderne Religion? : Jürgen Habermas und die Idee der "postsäkularen Gesellschaft"
(2009)
Das Verhältnis von Religion und Moderne ist in jüngster Zeit wieder zu einem heißen Konfliktherd geworden. So geht es beim Streit um die Piusbrüderschaft im Kern darum, ob eine religiöse Tradition die Kontinuität und Verbindlichkeit ihrer Überlieferung aufrechterhalten und zugleich an wesentliche Einsichten und normative Prinzipien der Moderne anschließen kann. Die traditionalistischen Kritiker des II. Vatikanischen Konzils behaupten, dass religiöse Institutionen wie die katholische Kirche ihre Identität in dem Maße verlieren, in dem sie ein bejahendes und konstruktives Verhältnis zur modernen Gesellschaft entwickeln. Die Anerkennung der Menschenrechte und der Ideen der Französischen Revolution durch das Konzil, also die Akzeptanz des Prinzips der Freiheit in Gestalt der Religionsfreiheit, der Gleichheit als Gleichberechtigung und Gleichwertigkeit aller Religionen und der Brüderlichkeit im Sinne einer gemeinsamen und solidarischen Weltverantwortung »aller Menschen guten Willens« bildet für die reaktionären Kritiker den eigentlichen Skandal der Öffnung der Kirche zur säkularen Moderne. Die unbeholfenen und viele empörenden Versuche der Resozialisierung der Piusbrüder sind letztlich unvollständige und unvollkommene Ansätze, auf eine kulturelle und gesellschaftliche Konstellation zu reagieren, für die Jürgen Habermas den prägnanten Ausdruck »postsäkulare Gesellschaft« geprägt hat. Diese Situation ist nach Habermas nämlich dadurch gekennzeichnet, dass sich religiöse Gemeinschaften auch in einer modernen Lebenswelt dauerhaft einrichten und in ihr fortbestehen. Wir haben laut Habermas Abschied zu nehmen von der Vorstellung eines linearen historischen Prozesses, der zwangsläufig zum Absterben der Religion führen wird. Allerdings schreitet die gesellschaftliche Säkularisierung im Sinne einer Ausdifferenzierung gesellschaftlicher Systeme und einer Pluralisierung von Weltanschauungen weiter voran.
Neurowissenschaftler fordern einen illusionslosen Umgang mit Begriffen wie Willensfreiheit und Bewusstsein. Philosophen kritisieren offen die Thesen von Hirnforschern. Stehen sich diese Positionen unversöhnlich gegenüber? Wo gibt es Möglichkeiten einer Annäherung, gar einer Kooperation? Der Religionsphilosoph Prof. Dr. Thomas M. Schmidt und der Biologe Stefan Kieß loten die Situation in Frankfurt aus; ihre Gesprächspartner sind der Hirnforscher Prof. Dr. Wolf Singer (links), Direktor am Max-Planck-Institut für Hirnforschung, und Prof. Dr. Marcus Willaschek (rechts), Philosoph an der Universität Frankfurt.
Holle, Henning ; Obermeier, Christian ; Schmidt-Kassow, Maren ; Friederici, Angela D. ; Ward, Jamie ; Gunter, Thomas C.
Recent research suggests that the brain routinely binds together information from gesture and speech. However, most of this research focused on the integration of representational gestures with the semantic content of speech. Much less is known about how other aspects of gesture, such as emphasis, influence the interpretation of the syntactic relations in a spoken message. Here, we investigated whether beat gestures alter which syntactic structure is assigned to ambiguous spoken German sentences. The P600 component of the Event Related Brain Potential indicated that the more complex syntactic structure is easier to process when the speaker emphasizes the subject of a sentence with a beat. Thus, a simple flick of the hand can change our interpretation of who has been doing what to whom in a spoken sentence. We conclude that gestures and speech are integrated systems. Unlike previous studies, which have shown that the brain effortlessly integrates semantic information from gesture and speech, our study is the first to demonstrate that this integration also occurs for syntactic information. Moreover, the effect appears to be gesture-specific and was not found for other stimuli that draw attention to certain parts of speech, including prosodic emphasis, or a moving visual stimulus with the same trajectory as the gesture. This suggests that only visual emphasis produced with a communicative intention in mind (that is, beat gestures) influences language comprehension, but not a simple visual movement lacking such an intention.
Immunosuppressive compounds affect the fungal growth and viability of defined aspergillus species
(2019)
Immunosuppressive drugs are administered to a number of patients; e.g., to allogeneic hematopoietic stem cell transplant recipients. Immunosuppressive drugs impair the immune system and thus increase the risk of invasive fungal disease, but may exhibit antifungal activity at the same time. We investigated the impact of various concentrations of three commonly used immunosuppressive compounds—cyclosporin A (CsA), methylprednisolone (mPRED), and mycophenolic acid (MPA)—on the growth and viability of five clinically important Aspergillus species. Methods included disc diffusion, optical density of mycelium, and viability assays such as XTT. MPA and CsA had a species-specific and dose-dependent inhibitory effect on the growth of all Aspergillus spp. tested, although growth inhibition by MPA was highest in A. niger, A. flavus and A. brasiliensis. Both agents exhibited species-specific hyphal damage, which was higher when the immunosuppressants were added to growing conidia than to mycelium. In contrast, mPRED increased the growth of A. niger, but had no major impact on the growth and viability of any of the other Aspergillus species tested. Our findings may help to better understand the interaction of drugs with Aspergillus species and ultimately may have an impact on individualizing immunosuppressive therapy.
Hohenforst-Schmidt, Wolfgang ; Zarogoulidis, Paul ; Özkan, Filiz ; Mahnkopf, Christian ; Grabenbauer, Gerhard ; Kreczy, Alfons ; Bartunek, Rudolf ; Darwiche, Kaid ; Freitag, Lutz ; Li, Qiang ; Huang, Haidong ; Vogl, Thomas J. ; LePilvert, Patrick ; Tsiouda, Theodora ; Tsakiridis, Kosmas ; Zarogoulidis, Konstantinos ; Brachmann, Johannes
Vasointestinal peptide metabolism plays a key physiological role in multimodular levels of vasodilatory, smooth muscle cell proliferative, parenchymal, and inflammatory lung reactions. In animal studies, vasointestinal peptide relaxes isolated pulmonary arterial segments from several mammalian species in vitro and neutralizes the pulmonary vasoconstrictor effect of endothelin. In some animal models, it reduces pulmonary vascular resistance in vivo and in monocrotaline-induced pulmonary hypertension. A 58-year-old woman presented with dyspnea and mild edema of the lower extremities. A bronchoscopy was performed without any suspicious findings suggesting a central tumor or other infiltrative disease. Endobronchial ultrasound revealed enlarged pulmonary arteries containing thrombi, a few enlarged lymph nodes, and enlarged mediastinal tissue anatomy with suspicion for mediastinal infiltration of a malignant process. We estimated that less than 10% of the peripheral vascular bed of the lung was involved in direct consolidated fibrosis as demonstrated in the left upper lobe apex. Further, direct involvement of fibrosis around the main stems of the pulmonary arteries was assumed to be low from positron emission tomography and magnetic resonance imaging scans. Assuming a positive influence of low-dose radiation, it was not expected that this could have reduced pulmonary vascular resistance by over two thirds of the initial result. However; it was noted that this patient had idiopathic pulmonary arterial hypertension mixed with "acute" (mediastinal) fibrosis which could have contributed to the unexpected success of reduction of pulmonary vascular resistance. To the best of our knowledge, this is the first report of successful treatment of idiopathic pulmonary arterial hypertension, probably as a result of low-dose radiation to the pulmonary arterial main stems. The patient continues to have no specific complaints concerning her idiopathic pulmonary arterial hypertension.
Hohenforst-Schmidt, Wolfgang ; Linsmeier, Bernd ; Zarogoulidis, Paul ; Freitag, Lutz ; Darwiche, Kaid ; Browning, Robert ; Turner, J. Francis ; Huang, Haidong ; Li, Qiang ; Vogl, Thomas J. ; Zarogoulidis, Konstantinos ; Brachmann, Johannes ; Rittger, Harald
Tracheomalacia or tracheobronchomalacia (TM or TBM) is a common problem especially for elderly patients often unfit for surgical techniques. Several surgical or minimally invasive techniques have already been described. Stenting is one option but in general long-time stenting is accompanied by a high complication rate. Stent removal is more difficult in case of self-expandable nitinol stents or metallic stents in general in comparison to silicone stents. The main disadvantage of silicone stents in comparison to uncovered metallic stents is migration and plugging. We compared the operation time and in particular the duration of a sufficient Dumon stent fixation with different techniques in a patient with severe posttracheotomy TM and strongly reduced mobility of the vocal cords due to Parkinson’s disease. The combined approach with simultaneous Dumon stenting and endoluminal transtracheal externalized suture under cone-beam computer tomography guidance with the Berci needle was by far the fastest approach compared to a (not performed) surgical intervention, or even purely endoluminal suturing through the rigid bronchoscope. The duration of the endoluminal transtracheal externalized suture was between 5 minutes and 9 minutes with the Berci needle; the pure endoluminal approach needed 51 minutes. The alternative of tracheobronchoplasty was refused by the patient. In general, 180 minutes for this surgical approach is calculated. The costs of the different approaches are supposed to vary widely due to the fact that in Germany 1 minute in an operation room costs on average approximately 50–60€ inclusive of taxes. In our own hospital (tertiary level), it is nearly 30€ per minute in an operation room for a surgical approach. Calculating an additional 15 minutes for patient preparation and transfer to wake-up room, therefore a total duration inside the investigation room of 30 minutes, the cost per flexible bronchoscopy is per minute on average less than 6€. Although the Dumon stenting requires a set-up with more expensive anesthesiology accompaniment, which takes longer than a flexible investigation estimated at 1 hour in an operation room, still without calculation of the costs of the materials and specialized staff that the surgical approach would consume at least 3,000€ more than a minimally invasive approach performed with the Berci needle. This difference is due to the longer time of the surgical intervention which is calculated at approximately 180 minutes in comparison to the achieved non-surgical approach of 60 minutes in the operation suite.
Hohenforst-Schmidt, Wolfgang ; Zarogoulidis, Paul ; Vogl, Thomas J. ; Turner, J. Francis ; Browning, Robert ; Linsmeier, Bernd ; Huang, Haidong ; Li, Qiang ; Darwiche, Kaid ; Freitag, Lutz ; Simoff, Michael ; Kioumis, Ioannis ; Zarogoulidis, Konstantinos ; Brachmann, Johannes
Introduction: Currently there are several advanced guiding techniques for pathoanatomical diagnosis of incidental solitary pulmonary nodules (iSPN): Electromagnetic navigation (EMN) with or without endobronchial ultrasound (EBUS) with miniprobe, transthoracic ultrasound (TTUS) for needle approach to the pleural wall and adjacent lung and computed tomography (CT) -guidance for (seldom if ever used) endobronchial or (common) transthoracical approach. In several situations one technique is not enough for efficient diagnosis, therefore we investigated a new diagnostic technique of endobronchial guided biopsies by a Cone Beam Computertomography (CBCT) called DynaCT (SIEMENS AG Forchheim, Germany). Method and Material: In our study 33 incidental solitary pulmonary nodules (iSPNs) (28 malignant, 5 benign; mean diameter 25 +/-12mm, shortest distance to pleura 25+/-18mm) were eligible according to in- and exclusion criteria. Realtime and onsite navigation were performed according to our standard protocol.22 All iSPN were controlled with a second technique when necessary and clinical feasible in case of unspecific or unexpected histological result. In all cases common guidelines of treatment of different iSPNs were followed in a routine manner. Results: Overall navigational yield (ny) was 91% and diagnostic yield (dy) 70%, dy for all accomplished malignant cases (n=28) was 82%. In the subgroup analysis of the invisible iSPN (n=12, 11 malignant, 1 benign; mean diameter 15+/-3mm) we found an overall dy of 75%. For the first time we describe a significant difference in specifity of biopsy results in regards to the position of the forceps in the 3-dimensional volume (3DV) of the iSPN in the whole sample group. Comparing the specifity of biopsies of a 3D-uncentered but inside the outer one third of an iSPN-3DV with the specifity of biopsies of centered forceps position (meaning the inner two third of an iSPN-3DV) reveals a significant (p=0,0375 McNemar) difference for the size group (>1cm) of 0,9 for centered biopsies vs. 0,3 for uncentered biopsies. Therefore only 3D-centered biopsies should be relied on especially in case of a benign result. Conclusion:The diagnostic yield of DynaCT navigation guided transbronchial biopsies (TBB) only with forceps is at least up to twofold higher than conventional TBB for iSPNs <2cm. The diagnostic yield of DynaCT navigation guided forceps TBB in invisible SPNs is at least in the range of other navigation studies which were performed partly with multiple navigation tools and multiple instruments. For future diagnostic and therapeutic approaches it is so far the only onsite and realtime extrathoracic navigation approach (except for computed tomography (CT)-fluoroscopy) in the bronchoscopy suite which keeps the working channel open. The system purchase represents an important investment for hospitals but it is a multidisciplinary and multinavigational tool with possible access via bronchial airways, transthoracical or vascular approach at the same time and on the same table without the need for an expensive disposable instrument use.
Background: Polyploidy and apomixis are important factors influencing plant distributions often resulting in range shifts, expansions and geographical parthenogenesis. We used the Ranunculus auricomus complex as a model to asses if the past and present distribution and climatic preferences were determined by these phenomena.
Results: Ecological differentiation among diploids and polyploids was tested by comparing the sets of climatic variables and distribution modelling using 191 novel ploidy estimations and 561 literature data. Significant differences in relative genome size on the diploid level were recorded between the “auricomus” and “cassubicus” groups and several new diploid occurrences were found in Slovenia and Hungary. The current distribution of diploids overlapped with the modelled paleodistribution (22 kyr BP), except Austria and the Carpathians, which are proposed to be colonized later on from refugia in the Balkans. Current and historical presence of diploids from the R. auricomus complex is suggested also for the foothills of the Caucasus. Based on comparisons of the climatic preferences polyploids from the R. auricomus complex occupy slightly drier and colder habitats than the diploids.
Conclusions: The change of reproductive mode and selection due to competition with the diploid ancestors may have facilitated the establishment of polyploids within the R. auricomus complex in environments slightly cooler and drier, than those tolerated by diploid ancestors. Much broader distribution of polyploid apomicts may have been achieved due to faster colonization mediated by uniparental reproductive system.
Es wird ueber neue Funde von Myrmecophilus acervorum in Bochum und Umgebung berichtet. Diese Fundorte
liegen außerhalb der bisher bekannten nordwestlichen Verbreitungsgrenze. Verbreitungskarten auf der Basis publizierter Daten zeigen die Ausbreitung nach Norden in den letzten Jahrzehnten. Ob und wie sich die Süedgrenze veraendert, laesst sich nicht feststellen, da die Unterscheidung von weiteren Arten unsicher ist.
Invasive fungal infections are still an important cause of morbidity and mortality in immunocompromised patients such as patients suffering from hematological malignancies or patients undergoing hematopoietic stem cell transplantion. In addition, other populations such as human immunodeficiency virus-patients are at higher risk for invasive fungal infection. Despite the availability of new antifungal compounds and better supportive care measures, the fatality rate of invasive fungal infection remained unacceptably high. It is therefore of major interest to improve our understanding of the host–pathogen interaction to develop new therapeutic approaches such as adoptive immunotherapy. As experimental methodologies have improved and we now better understand the complex network of the immune system, the insight in the interaction of the host with the fungus has significantly increased. It has become clear that host resistance to fungal infections is not only associated with strong innate immunity but that adaptive immunity (e.g., T cells) also plays an important role. The antifungal activity of natural killer (NK) cells has been underestimated for a long time. In vitro studies demonstrated that NK cells from murine and human origin are able to attack fungi of different genera and species. NK cells exhibit not only a direct antifungal activity via cytotoxic molecules but also an indirect antifungal activity via cytokines. However, it has been show that fungi exert immunosuppressive effects on NK cells. Whereas clinical data are scarce, animal models have clearly demonstrated that NK cells play an important role in the host response against invasive fungal infections. In this review, we summarize clinical data as well as results from in vitro and animal studies on the impact of NK cells on fungal pathogens.
Natural Killer (NK) cells are involved in the host immune response against infections due to viral, bacterial and fungal pathogens, all of which are a significant cause of morbidity and mortality in immunocompromised patients. Since the recovery of the immune system has a major impact on the outcome of an infectious complication, there is major interest in strengthening the host response in immunocompromised patients, either by using cytokines or growth factors or by adoptive cellular therapies transfusing immune cells such as granulocytes or pathogen-specific T-cells. To date, relatively little is known about the potential of adoptively transferring NK cells in immunocompromised patients with infectious complications, although the anti-cancer property of NK cells is already being investigated in the clinical setting. This review will focus on the antimicrobial properties of NK cells and the current standing and future perspectives of generating and using NK cells as immunotherapy in patients with infectious complications, an approach which is promising and might have an important clinical impact in the future.
Hoehndorf, Robert ; Alshahran, Mona ; Gkoutos, Georgios V. ; Gosline, George ; Groom, Quentin ; Hamann, Thomas ; Kattge, Jens ; Mota de Oliveira, Sylvia ; Schmidt, Marco ; Sierra, Soraya ; Smets, Erik ; Vos, Rutger Aldo ; Weiland, Claus
Background: The systematic analysis of a large number of comparable plant trait data can support investigations into phylogenetics and ecological adaptation, with broad applications in evolutionary biology, agriculture, conservation, and the functioning of ecosystems. Floras, i.e., books collecting the information on all known plant species found within a region, are a potentially rich source of such plant trait data. Floras describe plant traits with a focus on morphology and other traits relevant for species identification in addition to other characteristics of plant species, such as ecological affinities, distribution, economic value, health applications, traditional uses, and so on. However, a key limitation in systematically analyzing information in Floras is the lack of a standardized vocabulary for the described traits as well as the difficulties in extracting structured information from free text.
Results: We have developed the Flora Phenotype Ontology (FLOPO), an ontology for describing traits of plant species found in Floras. We used the Plant Ontology (PO) and the Phenotype And Trait Ontology (PATO) to extract entity-quality relationships from digitized taxon descriptions in Floras, and used a formal ontological approach based on phenotype description patterns and automated reasoning to generate the FLOPO. The resulting ontology consists of 25,407 classes and is based on the PO and PATO. The classified ontology closely follows the structure of Plant Ontology in that the primary axis of classification is the observed plant anatomical structure, and more specific traits are then classified based on parthood and subclass relations between anatomical structures as well as subclass relations between phenotypic qualities.
Conclusions: The FLOPO is primarily intended as a framework based on which plant traits can be integrated computationally across all species and higher taxa of flowering plants. Importantly, it is not intended to replace established vocabularies or ontologies, but rather serve as an overarching framework based on which different application- and domain-specific ontologies, thesauri and vocabularies of phenotypes observed in flowering plants can be integrated.
Trost, Martin ; Grosser, Norbert ; Hofmann, Thomas ; Jage, Horst ; Meyer, Frank ; Müller, Joachim ; Ohlendorf, Bernd ; Schmidt, Peter ; Schönborn, Christoph ; Steglich, Rosmarie ; Sy, Thoralf ; Vollmer, Alexander
Gemas Artikel 11 der FFH-Richtlinie ist ein Monitoring des Erhaltungszustandes der Arten von gemeinschaftlicher Bedeutung durchzufuhren. Weiterhin ist nach Artikel 12 eine fortlaufende Überwachung des unbeabsichtigten Fangs oder Tötens der Anhang IV-Tierarten vorgeschrieben, worauf gegebenenfalls weiterführende Erhaltungsmaßnahmen und Forschung aufbauen sollen. Im § 40 BNatSchG wird dieses Monitoring in die Verantwortung der Bundesländer übergeben.
Boden- und baumstammbewohnende Linyphiidae des Hienheimer Forstes (Bayern) (Arachnida: Araneae)
(1998)
This paper presents some results of a forest ecology research project by the University of Munich's faculty of Forestry, involving the comparison of forests designed to reflect varying degrees of naturalness. Spiders on the ground and on trunks in four different forests in the Hienheimer Forst were caught with 24 ground photo eclectors, 8 arboreal eclectors and with 40 pitfall traps. Habitat requirements were measured and analysed with particular attention to forest soil. Abiotic parameters and the structure of the litter layer were recorded. The most frequent spiders were the Linyphiidae, Agelenidae and Amaurobidae. 63 species of the family Linyphiidae were caught. One half of the Linyphiidae-species could be found on trunks of oak and spruce (eclector fauna). In terms of the number of spider species and in the portion of rare and endangered species there were almost no differences between commercial forest areas and conservation areas. The differences are not as great as the original classification according to closeness to the natural state had led us to expect.
Miehe, Susanne ; Crause, Peter ; Schmidt, Thorsten ; Löhn, Matthias ; Kleemann, Heinz-Werner ; Licher, Thomas ; Dittrich, Werner ; Rütten, Hartmut ; Strübing, Carsten
TRPC channels are a family of nonselective cation channels that regulate ion homeostasis and intracellular Ca2+ signaling in numerous cell types. Important physiological functions such as vasoregulation, neuronal growth, and pheromone recognition have been assigned to this class of ion channels. Despite their physiological relevance, few selective pharmacological tools are available to study TRPC channel function. We, therefore, screened a selection of pharmacologically active compounds for TRPC modulating activity. We found that the synthetic gestagen norgestimate inhibited diacylglycerol-sensitive TRPC3 and TRPC6 with IC50s of 3–5 µM, while half-maximal inhibition of TRPC5 required significantly higher compound concentrations (>10 µM). Norgestimate blocked TRPC-mediated vasopressin-induced cation currents in A7r5 smooth muscle cells and caused vasorelaxation of isolated rat aorta, indicating that norgestimate could be an interesting tool for the investigation of TRP channel function in native cells and tissues. The steroid hormone progesterone, which is structurally related to norgestimate, also inhibited TRPC channel activity with IC50s ranging from 6 to 18 µM but showed little subtype selectivity. Thus, TRPC channel inhibition by high gestational levels of progesterone may contribute to the physiological decrease of uterine contractility and immunosuppression during pregnancy.
Dass Universitätsbauten in Frankfurt stilbildend sind, sieht jeder Besucher auf dem Campus Westend. Auch auf dem Riedberg, wo die Naturwissenschaftler ihren Campus haben, lernen die Studenten in hochwertigen Gebäuden. 152,4 Millionen Euro kosteten die drei Gebäude der zweiten Bauphase. Gestern wurden sie eingeweiht.
Bönsel, Dirk ; Jong, Martin de ; Dyballa, Peter ; Ehmke, Wolfgang ; Emrich, Peter ; Feller, Benjamin ; Göbel, Brunhilde ; Gregor, Thomas ; Hodvina, Sylvain ; Kasperek, Gerwin ; Korte, Egbert ; Egbert, Ute ; Meyer, Stefan ; Nesemann, Hasko Friedrich ; Raabe, Uwe ; Sauerwein, Bernd ; Schmidt, Marco ; Schröder, Christof Nikolaus ; Schwab, Antje ; Stoodt, Rainer ; Uebeler, Michael
Die Fundmeldungen in Band 33 von Botanik und Naturschutz in Hessen stammen von: Dirk Bönsel, Martin de Jong, Wolfgang Ehmke, Peter Emrich, Benjamin Feller, Brunhilde Göbel, Thomas Gregor, Arthur Händler, Sylvain Hodvina, Gerwin Kasperek, Egbert Korte, Ute Lange, Stefan Meyer, Hasko Friedrich Nesemann, Uwe Raabe, Bernd Sauerwein, Marco Schmidt, Christof Nikolaus Schröder, Antje Schwab, Rainer Stoodt und Michael Uebeler.
Eckert, Joachim Philipp ; Schmidt, Marco ; Magedanz, Annett ; Voigtländer, Thomas ; Schmermund, Axel
Invasive coronary angiography (ICA) was the only method to image coronary arteries for a long time and is still the gold-standard. Technology of noninvasive imaging by coronary computed-tomography angiography (CCTA) has experienced remarkable progress during the last two decades. It is possible to visualize atherosclerotic lesions in the vessel wall in contrast to "lumenography" performed by ICA. Coronary artery disease can be ruled out by CCTA with excellent accuracy. The degree of stenoses is, however, often overestimated which impairs specificity. Atherosclerotic lesions can be characterized as calcified, non-calcified and partially calcified. Calcified plaques are usually quantified using the Agatston-Score. Higher scores are correlated with worse cardiovascular outcome and increased risk of cardiac events. For non-calcified or partially calcified plaques different angiographic findings like positive remodelling, a large necrotic core or spotty calcification more frequently lead to myocardial infarctions. CCTA is an important tool with increasing clinical value for ruling out coronary artery disease or relevant stenoses as well as for advanced risk stratification.
Boehncke, Wolf-Henning ; Elshorst-Schmidt, Thomas ; Kleinhans, Martin ; Köberich, Vanessa Carena ; Kaufmann, Roland
Fragestellung Intoleranzreaktionen auf nicht-steroidale Antiphlogistika sind häufig und basieren auf der Hemmung des Enzyms Cyclooxygenase-1 (COX-1), wohingegen deren therapeutische Effekte auf einer COX-2 Hemmung beruhen. In dieser Studie wurde die Verträglichkeit des selektiven COX-2 Inhibitors Celecoxib bei Patienten mit Intoleranzreaktionen auf nicht-steroidale Antiphlogistika untersucht. Methodik Bei 77 Patienten (24 Männer, 53 Frauen) mit Intoleranzreaktionen auf nicht-steroidale Antiphlogistika wurden standardisierte Hauttestungen (Prick, Scratch, Epikutantestung) sowie anschließend orale fraktionierte Placebo-kontrollierte einfach blinde Expositionstestungen unter Einschluß von Celecoxib (maximale Einzeldosis 200mg, kumukative Tagesdosis 350mg) durchgeführt. Ergebnisse 21 Patienten wiesen anamnestisch lediglich Hautsymptome (Urtikaria) auf, 25 Patienten nur eine Atemwegssymptomatik (Asthma), bei 18 Patienten traten Haut- und Atemwegssymptome auf, und bei 13 Patienten war es zu einem anaphylaktischen Schock gekommen. Azetylsalizylsäure war in 38 Fällen ein Auslöser der Beschwerden. In 46 Fällen verursachten mehrere nicht-steroidale Antiphlogistika chemisch unterschiedlicher Gruppen die Symptomatik. Die orale Expositionstestung mit Celecoxib verlief bei allen 77 Patienten unauffällig. Schlußfolgerung Vor dem Hintergrund der hohen Inzidenz von Intoleranzreaktionen gegen nicht-steroidale Antiphlogistika stellt der Einsatz selektiver COX-2 Inhibitoren eine therapeutische Alternative sowie eine geeignete Maßnahme zur Prävention entsprechender Reaktionen dar.
Bönsel, Dirk ; Jong, Martin de ; Dühr, Klaus ; Engel, Uta ; Feller, Benjamin ; Feuring, Christian ; Gregor, Thomas ; Händler, Arthur ; Horn, Karsten ; Klärner, Diemut ; Kruse, Julia Marlene ; Martiné, Eric ; Nesemann, Hasko Friedrich ; Nierbauer, Kai Uwe ; Raabe, Uwe ; Raehse, Susanne ; Reischmann, Felix ; Sauerwein, Bernd ; Schmidt, Petra ; Schrauth, Fabian Etienne ; Schröder, Christof Nikolaus ; Siebert, Helmut ; Thieme, Michael ; Wacker, Otto ; Wittig, Rüdiger
Die Fundmeldungen in Band 34 von Botanik und Naturschutz in Hessen stammen von: Dirk Bönsel, Martin De Jong, Klaus Dühr, Uta Engel, Benjamin Feller, Christian Feuring, Thomas Gregor, Arthur Händler, Karsten Horn, Diemut Klärner, Julia Kruse, Eric Martiné, Hasko Friedrich Nesemann, Kai Uwe Nierbauer, Uwe Raabe, Susanne Raehse, Felix Reischmann, Bernd Sauerwein, Petra Schmidt, Fabian Schrauth, Christof Nikolaus Schröder, Helmut Siebert, Michael Thieme, Otto Wacker und Rüdiger Wittig.
Neozoa werden als gebietsfremde Arten definiert, welche nach 1492 direkt oder indirekt durch den Menschen eingeführt wurden und selbstreproduzierende Populationen zu bilden im Stande sind (Essl & Rabitsch 2002). Biologische Invasionen sind schon seit dem Zeitalter des Kolonialismus ein bekanntes Phänomen, gegenwärtig hat das Problem in einer Zeit der Globalisierung von Wirtschaft und Tourismus und einer globalen Klimaveränderung jedoch eine neue Dimension und Geschwindigkeit erreicht. In Österreich gibt es grundsätzlich eine gute Datenbasis über das Auftreten von benthischen Einwanderern. Bereits in der älteren Literatur findet man dazu einige Hinweise, z.B.: Strouhal (1939), Vornatscher (1965) und Liepolt (1965–67). Größere Aufmerksamkeit wurde dem Phänomen invasiver Arten seit der massiven Ausbreitung der Dreikantmuschel Dreissena polymorpha geschenkt, als sich diese in den 1970er Jahren in vielen Flüssen und Seen in einem sehr kurzen Zeitraum ausbreitete. Verstärkte Beachtung wurde den Neozoa in der Limnologie aber erst im letzten Jahrzehnt zuteil, als die Fundnachweise immer häufiger wurden und sowohl ökonomische als auchbemerkenswerte ökologische Auswirkungen durch invasive Arten vermutet oder nachgewiesen wurden. Beispielsweise belegte Gruber (2006), dass der autochthone Steinkrebs (Austropotamobius torrentium) bereits bis in die Quellregion hinein durch den amerikanischen Signalkrebs (Pacifastacus leniusculus) verdrängt wird. In Österreich entstand als Folge des erhöhten Problembewusstseins in den letzten Jahren eine Reihe von umfassenden Publikationen zum Thema Neobiota: „Invaders“ (Aescht & al. 1995), „Neobiota in Österreich“ (Essl & Rabitsch 2002) und „Aliens“ (Wallner 2005). Während die überwiegende Zahl der Publikationen zum Thema Neozoa von taxonomischen Fachspezialisten stammt und deshalb zumeist auf eine oder einige ausgewählte Tiergruppen beschränkt bleibt, basiert vorliegender Beitrag auf Monitoringdaten und gewässerökologischen Untersuchungen, in welchen immer die gesamte Artengesellschaft der benthischen Evertebraten erhoben wurde.
Schmidt, Susan ; Schneider, Johannes ; Klimach, Thomas ; Mertes, Stephan ; Schenk, Ludwig Paul ; Kupiszewski, Piotr ; Curtius, Joachim ; Borrmann, Stephan
In situ single particle analysis of ice particle residuals (IPRs) and out-of-cloud aerosol particles was conducted by means of laser ablation mass spectrometry during the intensive INUIT-JFJ/CLACE campaign at the high alpine research station Jungfraujoch (3580 m a.s.l.) in January–February 2013. During the 4-week campaign more than 70 000 out-of-cloud aerosol particles and 595 IPRs were analyzed covering a particle size diameter range from 100 nm to 3 µm. The IPRs were sampled during 273 h while the station was covered by mixed-phase clouds at ambient temperatures between −27 and −6 °C. The identification of particle types is based on laboratory studies of different types of biological, mineral and anthropogenic aerosol particles. The outcome of these laboratory studies was characteristic marker peaks for each investigated particle type. These marker peaks were applied to the field data. In the sampled IPRs we identified a larger number fraction of primary aerosol particles, like soil dust (13 ± 5 %) and minerals (11 ± 5 %), in comparison to out-of-cloud aerosol particles (2.4 ± 0.4 and 0.4 ± 0.1 %, respectively). Additionally, anthropogenic aerosol particles, such as particles from industrial emissions and lead-containing particles, were found to be more abundant in the IPRs than in the out-of-cloud aerosol. In the out-of-cloud aerosol we identified a large fraction of aged particles (31 ± 5 %), including organic material and secondary inorganics, whereas this particle type was much less abundant (2.7 ± 1.3 %) in the IPRs. In a selected subset of the data where a direct comparison between out-of-cloud aerosol particles and IPRs in air masses with similar origin was possible, a pronounced enhancement of biological particles was found in the IPRs.
Schmidt, Susan ; Schneider, Johannes ; Klimach, Thomas ; Mertes, Stephan ; Schenk, Ludwig Paul ; Kupiszewski, Piotr ; Curtius, Joachim ; Borrmann, Stephan
In-situ single particle analysis of ice particle residuals (IPR) and out-of-cloud aerosol particles was conducted by means of laser ablation mass spectrometry during the intensive INUIT-JFJ/CLACE campaign at the high alpine research station Jungfraujoch (3580 m a.s.l.) in January/February 2013. During the four week campaign more than 70000 out-of-cloud aerosol particles and 595 IPR were analyzed covering a particle size diameter range from 100 nm to 3 μm. The IPR were sampled during 273 hours while the station was covered by mixed-phase clouds at ambient temperatures between -27 °C and -6 °C. The identification of particle types is based on laboratory studies of different types of biological, mineral and anthropogenic aerosol particles. As outcome instrument specific marker peaks for the different investigated particle types were obtained and applied to the field data. The results show that the sampled IPR contain a larger relative amount of natural, primary aerosol, like soil dust (13 %) and minerals (11 %), in comparison to out-of-cloud aerosol particles (2 % and <1 %, respectively). Additionally, anthropogenic aerosol particles, like particles from industrial emissions and lead-containing particles, were found to be more abundant in the IPR than in the out-of-cloud aerosol. The out of-cloud aerosol contained a large fraction of aged particles (30 %, including organic material and secondary inorganics), whereas this particle type was much less abundant (3 %) in the IPR. In a selected subset of the data where a direct comparison between out-of-cloud aerosol particles and IPR in air masses with similar origin was possible, a pronounced enhancement of biological particles was found in the IPR.
Kowark, Ana ; Adam, Christian ; Ahrens, Jörg ; Bajbouj, Malek ; Bollheimer, Cornelius ; Borowski, Matthias ; Dodel, Richard ; Dolch, Michael ; Hachenberg, Thomas ; Henzler, Dietrich ; Hildebrand, Frank ; Hilgers, Ralf-Dieter ; Hoeft, Andreas ; Isfort, Susanne ; Kienbaum, Peter ; Knobe, Mathias ; Knüfermann, Pascal ; Kranke, Peter ; Laufenberg-Feldmann, Rita ; Nau, Carla ; Neuman, Mark D. ; Olotu, Cynthia ; Rex, Christopher ; Rossaint, Rolf ; Sanders, Robert D. ; Schmidt, Rene ; Schneider, Frank ; Siebert, Hartmut ; Skorning, Max ; Spies, Claudia ; Vicent, Oliver ; Wappler, Frank ; Wirtz, Dieter Christian ; Wittmann, Maria ; Zacharowski, Kai ; Zarbock, Alexander ; Coburn, Mark
Introduction: Hip fracture surgery is associated with high in-hospital and 30-day mortality rates and serious adverse patient outcomes. Evidence from randomised controlled trials regarding effectiveness of spinal versus general anaesthesia on patient-centred outcomes after hip fracture surgery is sparse.
Methods and analysis: The iHOPE study is a pragmatic national, multicentre, randomised controlled, open-label clinical trial with a two-arm parallel group design. In total, 1032 patients with hip fracture (>65 years) will be randomised in an intended 1:1 allocation ratio to receive spinal anaesthesia (n=516) or general anaesthesia (n=516). Outcome assessment will occur in a blinded manner after hospital discharge and inhospital. The primary endpoint will be assessed by telephone interview and comprises the time to the first occurring event of the binary composite outcome of all-cause mortality or new-onset serious cardiac and pulmonary complications within 30 postoperative days. In-hospital secondary endpoints, assessed via in-person interviews and medical record review, include mortality, perioperative adverse events, delirium, satisfaction, walking independently, length of hospital stay and discharge destination. Telephone interviews will be performed for long-term endpoints (all-cause mortality, independence in walking, chronic pain, ability to return home cognitive function and overall health and disability) at postoperative day 30±3, 180±45 and 365±60.
Ethics and dissemination: iHOPE has been approved by the leading Ethics Committee of the Medical Faculty of the RWTH Aachen University on 14 March 2018 (EK 022/18). Approval from all other involved local Ethical Committees was subsequently requested and obtained. Study started in April 2018 with a total recruitment period of 24 months. iHOPE will be disseminated via presentations at national and international scientific meetings or conferences and publication in peer-reviewed international scientific journals.
Trial registration number: DRKS00013644; Pre-results
Waldvogel, Ann-Marie ; Wieser, Andreas ; Schell, Tilman ; Patel, Simit ; Schmidt, Hanno ; Hankeln, Thomas ; Feldmeyer, Barbara ; Pfenninger, Markus
The gradual heterogeneity of climatic factors pose varying selection pressures across geographic distances that leave signatures of clinal variation in the genome. Separating signatures of clinal adaptation from signatures of other evolutionary forces, such as demographic processes, genetic drift, and adaptation to non-clinal conditions of the immediate local environment is a major challenge. Here, we examine climate adaptation in five natural populations of the harlequin fly Chironomus riparius sampled along a climatic gradient across Europe. Our study integrates experimental data, individual genome resequencing, Pool-Seq data, and population genetic modelling. Common-garden experiments revealed a positive correlation of population growth rates corresponding to the population origin along the climate gradient, suggesting thermal adaptation on the phenotypic level. Based on a population genomic analysis, we derived empirical estimates of historical demography and migration. We used an FST outlier approach to infer positive selection across the climate gradient, in combination with an environmental association analysis. In total we identified 162 candidate genes as genomic basis of climate adaptation. Enriched functions among these candidate genes involved the apoptotic process and molecular response to heat, as well as functions identified in other studies of climate adaptation in other insects. Our results show that local climate conditions impose strong selection pressures and lead to genomic adaptation despite strong gene flow. Moreover, these results imply that selection to different climatic conditions seems to converge on a functional level, at least between different insect species.
Genomic basis of ecological niche divergence among cryptic sister species of non-biting midges
(2013)
Schmidt, Hanno ; Tzovaras, Bastian Greshake ; Feldmeyer, Barbara ; Hankeln, Thomas ; Pfenninger, Markus
Background: There is a lack of understanding the evolutionary forces driving niche segregation of closely related organisms. In addition, pinpointing the genes driving ecological divergence is a key goal in molecular ecology. Here, larval transcriptome sequences obtained by next-generation-sequencing are used to address these issues in a morphologically cryptic sister species pair of non-biting midges (Chironomus riparius and C. piger).
Results: More than eight thousand orthologous open reading frames were screened for interspecific divergence and intraspecific polymorphisms. Despite a small mean sequence divergence of 1.53% between the sister species, 25.1% of 18,115 observed amino acid substitutions were inferred by α statistics to be driven by positive selection. Applying McDonald-Kreitman tests to 715 alignments of gene orthologues identified eleven (1.5%) genes driven by positive selection.
Conclusions: Three candidate genes were identified as potentially responsible for the observed niche segregation concerning nitrite concentration, habitat temperature and water conductivity. Additionally, signs of positive selection in the hydrogen sulfide detoxification pathway were detected, providing a new plausible hypothesis for the species’ ecological differentiation. Finally, a divergently selected, nuclear encoded mitochondrial ribosomal protein may contribute to reproductive isolation due to cytonuclear coevolution.
Fiebiger, Stefan ; Slavkovská, Zuzana ; Giesen, Ulrich ; Göbel, Kathrin ; Heftrich, Tanja ; Heiske, Annett ; Reifarth, René ; Schmidt, Stefan ; Sonnabend, Kerstin ; Thomas, Benedikt ; Weigand, Mario
The production of 77,79,85,85mKr and 77Br via the reaction Se(a, x) was investigated between Ea = 11 and 15 MeV using the activation technique. The irradiation of natural selenium targets on aluminum backings was conducted at the Physikalisch-Technische Bundesanstalt (PTB) in Braunschweig, Germany. The spectroscopic analysis of the reaction products was performed using a high-purity germanium detector located at PTB and a low energy photon spectrometer detector at the Goethe University Frankfurt, Germany. Thicktarget yields were determined. The corresponding energy-dependent production cross sections of 77,79,85,85mKr and 77Br were calculated from the thicktarget yields. Good agreement between experimental data and theoretical predictions using the TALYS-1.6 code was found.
Hartke, Juliane ; Schell, Tilman ; Jongepier, Evelien ; Schmidt, Hanno ; Sprenger, Philipp P. ; Paule, Juraj ; Bornberg-Bauer, Erich ; Schmitt, Thomas ; Menzel, Florian ; Pfenninger, Markus ; Feldmeyer, Barbara
The success of social insects is largely intertwined with their highly advanced chemical communication system that facilitates recognition and discrimination of species and nest-mates, recruitment, and division of labor. Hydrocarbons, which cover the cuticle of insects, not only serve as waterproofing agents but also constitute a major component of this communication system. Two cryptic Crematogaster species, which share their nest with Camponotus ants, show striking diversity in their cuticular hydrocarbon (CHC) profile. This mutualistic system therefore offers a great opportunity to study the genetic basis of CHC divergence between sister species. As a basis for further genome-wide studies high-quality genomes are needed. Here, we present the annotated draft genome for Crematogaster levior A. By combining the three most commonly used sequencing techniques—Illumina, PacBio, and Oxford Nanopore—we constructed a high-quality de novo ant genome. We show that even low coverage of long reads can add significantly to overall genome contiguity. Annotation of desaturase and elongase genes, which play a role in CHC biosynthesis revealed one of the largest repertoires in ants and a higher number of desaturases in general than in other Hymenoptera. This may provide a mechanistic explanation for the high diversity observed in C. levior CHC profiles.
Schmidt, Susan ; Schneider, Johannes ; Klimach, Thomas ; Mertes, Stephan ; Schenk, Ludwig P. ; Curtius, Joachim ; Kupiszewski, Piotr ; Hammer, Emanuel ; Vochezer, Paul ; Lloyd, Gary ; Ebert, Martin ; Kandler, Konrad ; Weinbruch, Stephan ; Borrmann, Stephan
This paper presents results from the "INUIT-JFJ/CLACE 2013" field campaign at the high alpine research station Jungfraujoch in January/February 2013. The chemical composition of ice particle residuals (IPR) in a size diameter range of 200–900 nm was measured in orographic, convective and non-convective clouds with a single particle mass spectrometer (ALABAMA) under ambient conditions characterized by temperatures between −28 and −4 °C and wind speed from 0.1 to 21 km h−1. Additionally, background aerosol particles in cloud free air were investigated. The IPR were sampled from mixed-phase clouds with two inlets which selectively extract small ice crystals in-cloud, namely the Counterflow Virtual Impactor (Ice-CVI) and the Ice Selective Inlet (ISI). The IPR as well as the aerosol particles were classified into seven different particle types: (1) black carbon, (2) organic carbon, (3) black carbon internally mixed with organic carbon, (4) minerals, (5) one particle group (termed "BioMinSal") that may contain biological particles, minerals, or salts, (6) industrial metals, and (7) lead containing particles. For any sampled particle population it was determined by means of single particle mass spectrometer how many of the analyzed particles belonged to each of these categories. Accordingly, between 20 and 30% of the IPR and roughly 42% of the background particles contained organic carbon. The measured fractions of minerals in the IPR composition varied from 6 to 33%, while the values for the "BioMinSal" group were between 15 and 29%. Four percent to 31% of the IPR contained organic carbon mixed with black carbon. Both inlets delivered similar results of the chemical composition and of the particle size distribution, although lead was found only in the IPR sampled by the Ice-CVI. The results show that the ice particle residual composition varies substantially between different cloud events, which indicates the influence of different meteorological conditions, such as origin of the air masses, temperature and wind speed.
Grass savannas on lateritic crusts are characteristic landscape elements of the Sudanian savannas. In the W National Park and its surroundings in SE-Burkina Faso, plant diversity of savannas on and adjacent to bowé was assessed by a survey of 19 bowal areas with relevés along transects in each of these. The vegetation structure and species composition of the herb and shrub strata, soil depth, particle size and the concentration of Na+, K+, Mg2+, Ca2+, H+, C and N were recorded on each bowal and its surroundings. Our results show that soils on lateritic crusts are rather shallow and acidic compared to the surrounding savanna woodlands. Nutrient availability is hence comparatively low. The observed flora comprises 130 species mainly belonging to the families Combretaceae, Cyperaceae, Leguminosae and Poaceae with a predominance of therophytes and a comparatively high share of C4 species. In the pastures surrounding the National Park a higher species richness was found than inside the Park due to the occurrence of pioneers, ruderal and unpalatable plants. Savannas on lateritic crusts exhibit due to their extreme edaphic and hydrological conditions a specific flora distinct from their surroundings.
Mousset, Sabine ; Buchheidt, Dieter ; Heinz, Werner ; Ruhnke, Markus ; Cornely, Oliver Andreas ; Egerer, Gerlinde ; Krüger, William ; Link, Hartmut ; Neumann, Silke ; Ostermann, Helmut ; Panse, Jens ; Penack, Olaf ; Rieger, Christina ; Schmidt-Hieber, Martin ; Silling, Gerda ; Südhoff, Thomas ; Ullmann, Andrew J. ; Wolf, Hans-Heinrich ; Maschmeyer, Georg ; Böhme, Angelika
The Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO) here presents its updated recommendations for the treatment of documented fungal infections. Invasive fungal infections are a main cause of morbidity and mortality in cancer patients undergoing intensive chemotherapy regimens. In recent years, new antifungal agents have been licensed, and agents already approved have been studied in new indications. The choice of the most appropriate antifungal treatment depends on the fungal species suspected or identified, the patient’s risk factors (e.g., length and depth of neutropenia), and the expected side effects. This guideline reviews the clinical studies that served as a basis for the following recommendations. All recommendations including the levels of evidence are summarized in tables to give the reader rapid access to the information.
Herden, Uta ; Schöning, Wenzel ; Pratschke, Johann ; Manekeller, Steffen ; Paul, Andreas ; Linke, Richard ; Lorf, Thomas ; Lehner, Frank ; Braun, Felix ; Stippel, Dirk ; Sucher, Robert ; Schmidt, Hartmut ; Straßburg, Christian P. ; Guba, Markus ; Rosmalen, Marieke van ; Rogiers, Xavier ; Samuel, Undine ; Schön, Gerhard ; Nashan, Björn
Selection and prioritization of patients with HCC for LT are based on pretransplant imaging diagnostic, taking the risk of incorrect diagnosis. According to the German waitlist guidelines, imaging has to be reported to the allocation organization (Eurotransplant) and pathology reports have to be submitted thereafter. In order to assess current procedures we performed a retrospective multicenter analysis in all German transplant centers with focus on accuracy of imaging diagnostic and tumor classification. 1168 primary LT for HCC were conducted between 2007 and 2013 in Germany. Patients inside the Milan, UCSF, and up-to-seven criteria were misclassified with definitive histologic results in 18%, 15%, and 11%, respectively. Patients pretransplant outside the Milan, UCSF, and up-to-seven criteria were otherwise misclassified in 34%, 43%, and 41%. Recurrence-free survival correlated with classification by posttransplant histological report, but not pretransplant imaging diagnostic. Univariate analysis revealed tumor size, vascular invasion, and grading as significant parameters for outcome, while tumor grading was the only parameter persisting by multivariate testing. Conclusion. There was a relevant percentage (15-40%) of patients misclassified by imaging diagnosis at a time prior to LI-RADS and guidelines to improve imaging of HCC. Outcome analysis showed a good correlation to histological, in contrast poor correlation to imaging diagnosis, suggesting an adjustment of the LT selection and prioritization criteria.
Weiland, Claus ; Driller, Christine ; Koch, Markus ; Schmidt, Marco ; Abrami, Giuseppe ; Ahmed, Sajawel ; Mehler, Alexander ; Pachzelt, Adrian ; Kasperek, Gerwin ; Hausinger, Angela ; Hörnschemeyer, Thomas
With the ongoing loss of global biodiversity, long-term recordings of species distribution patterns are increasingly becoming important to investigate the causes and consequences for their change. Therefore, the digitization of scientific literature, both modern and historical, has been attracting growing attention in recent years. To meet this growing demand the Specialised Information Service for Biodiversity Research (BIOfid) was launched in 2017 with the aim of increasing the availability and accessibility of biodiversity information. Closely tied to the research community the interdisciplinary BIOfid team is digitizing data sources of biodiversity related research and provides a modern and professional infrastructure for hosting and sharing them. As a pilot project, German publications on the distribution and ecology of vascular plants, birds, moths and butterflies covering the past 250 years are prioritized. Large parts of the text corpus defined in accordance with the needs of the relevant German research community have already been transferred to a machine-readable format and will be publicly accessible soon. Software tools for text mining, semantic annotation and analysis with respect to the current trends in machine learning are developed to maximize bioscientific data output through user-specific queries that can be created via the BIOfid web portal (https://www.biofid.de/). To boost knowledge discovery, specific ontologies focusing on morphological traits and taxonomy are being prepared and will continuously be extended to keep up with an ever-expanding volume of literature sources.
Sekulovski, Samoil ; Devant, Pascal ; Panizza, Silvia ; Gogakos, Tasos ; Pitiriciu, Anda ; Heitmeier, Katharina ; Ramsay, Ewan Phillip ; Barth, Marie ; Schmidt, Carla ; Weitzer, Stefan ; Tuschl, Thomas ; Baas, Frank ; Martinez, Javier ; Trowitzsch, Simon
Introns of human transfer RNA precursors (pre-tRNAs) are excised by the tRNA splicing endonuclease TSEN in complex with the RNA kinase CLP1. Mutations in TSEN/CLP1 occur in patients with pontocerebellar hypoplasia (PCH), however, their role in the disease is unclear. Here, we show that intron excision is catalyzed by tetrameric TSEN assembled from inactive heterodimers independently of CLP1. Splice site recognition involves the mature domain and the anticodon-intron base pair of pre-tRNAs. The 2.1-Å resolution X-ray crystal structure of a TSEN15–34 heterodimer and differential scanning fluorimetry analyses show that PCH mutations cause thermal destabilization. While endonuclease activity in recombinant mutant TSEN is unaltered, we observe assembly defects and reduced pre-tRNA cleavage activity resulting in an imbalanced pre-tRNA pool in PCH patient-derived fibroblasts. Our work defines the molecular principles of intron excision in humans and provides evidence that modulation of TSEN stability may contribute to PCH phenotypes.
Bremm, Melanie ; Pfeffermann, Lisa-Marie ; Cappel, Claudia ; Katzki, Verena ; Erben, Stephanie ; Betz, Sibille ; Quaiser, Andrea ; Merker, Michael ; Bönig, Halvard-Björn ; Schmidt, Michael ; Klingebiel, Thomas ; Bader, Peter ; Hünecke, Sabine ; Rettinger, Eva
Cytokine-induced killer (CIK) cells are an immunotherapeutic approach to combat relapse following allogeneic hematopoietic stem cell transplantation (HSCT) in acute leukemia or myelodysplastic syndrome (MDS) patients. Prompt and sequential administration of escalating cell doses improves the efficacy of CIK cell therapy without exacerbating graft vs. host disease (GVHD). This study addresses manufacturing-related issues and aimed to develop a time-, personal- and cost-saving good manufacturing process (GMP)-compliant protocol for the generation of ready-for-use therapeutic CIK cell doses starting from one unstimulated donor-derived peripheral blood (PB) or leukocytapheresis (LP) products. Culture medium with or without the addition of either AB serum, fresh frozen plasma (FFP) or platelet lysate (PL) was used for culture. Fresh and cryopreserved CIK cells were compared regarding expansion rate, viability, phenotype, and ability to inhibit leukemia growth. Cell numbers increased by a median factor of 10-fold in the presence of FFP, PL, or AB serum, whereas cultivation in FFP/PL-free or AB serum-free medium failed to promote adequate CIK cell proliferation (p < 0.01) needed to provide clinical doses of 1 × 106 T cells/kG, 5 × 106 T cells/kG, 1 × 107 T cells/kG, and 1 × 108 T cells/kG recipient body weight. CIK cells consisting of T cells, T- natural killer (T-NK) cells and a minor fraction of NK cells were not significantly modified by different medium supplements. Moreover, neither cytotoxic potential against leukemic THP-1 cells nor cell activation shown by CD25 expression were significantly influenced. Moreover, overnight and long-term cryopreservation had no significant effect on the composition of CIK cells, their phenotype or cytotoxic potential. A viability of almost 93% (range: 89–96) and 89.3% (range: 84–94) was obtained after freeze-thawing procedure and long-term storage, respectively, whereas viability was 96% (range: 90-97) in fresh CIK cells. Altogether, GMP-complaint CIK cell generation from an unstimulated donor-derived PB or LP products was feasible. Introducing FFP, which is easily accessible, into CIK cell cultures was time- and cost-saving without loss of viability and potency in a 10-12 day batch culture. The feasibility of cryopreservation enabled storage and delivery of sequential highly effective ready-for-use CIK cell doses and therefore reduced the number of manufacturing cycles.
Sekulovski, Samoil ; Devant, Pascal ; Panizza, Silvia ; Gogakos, Tasos ; Pitiriciu, Anda ; Heitmeier, Katharina ; Ramsay, Ewan Phillip ; Barth, Marie ; Schmidt, Carla ; Tuschl, Thomas ; Baas, Frank ; Weitzer, Stefan ; Martinez, Javier ; Trowitzsch, Simon
Introns of human transfer RNA precursors (pre-tRNAs) are excised by the tRNA splicing endonuclease TSEN in complex with the RNA kinase CLP1. Mutations in TSEN/CLP1 occur in patients with pontocerebellar hypoplasia (PCH), however, their role in the disease is unclear. Here, we show that intron excision is catalyzed by tetrameric TSEN assembled from inactive heterodimers independently of CLP1. Splice site recognition involves the mature domain and the anticodon-intron base pair of pre-tRNAs. The 2.1-Å resolution X-ray crystal structure of a TSEN15–34 heterodimer and differential scanning fluorimetry analyses show that PCH mutations cause thermal destabilization. While endonuclease activity in recombinant mutant TSEN is unaltered, we observe assembly defects and reduced pre-tRNA cleavage activity resulting in an imbalanced pre-tRNA pool in PCH patient-derived fibroblasts. Our work defines the molecular principles of intron excision in humans and provides evidence that modulation of TSEN stability may contribute to PCH phenotypes.
Schnitzbauer, Andreas ; Zuelke, Carl ; Graeb, Christian ; Rochon, Justine ; Bilbao, Itxarone ; Burra, Patrizia ; de Jong, Koert P. ; Duvoux, Christophe ; Kneteman, Norman M. ; Adam, Rene ; Bechstein, Wolf Otto ; Becker, Thomas ; Beckebaum, Susanne ; Chazouilleres, Olivier ; Cillo, Umberto ; Colledan, Michele ; Fandrich, Fred ; Gugenheim, Jean ; Hauss, Johann P. ; Heise, Michael ; Hidalgo, Ernest ; Jamieson, Neville ; Königsrainer, Alfred ; Lamby, Philipp E. ; Lerut, Jan P. ; Makisalo, Heikki ; Margreiter, Raimund ; Mazzaferro, Vincenzo ; Mutzbauer, Ingrid ; Otto, Gerd ; Pageaux, Georges-Philippe ; Pinna, Antonio D. ; Pirenne, Jacques ; Rizell, Magnus ; Rossi, Giorgio ; Rostaing, Lionel ; Roy, Andre ; Turrion, Victor Sanchez ; Schmidt, Jan ; Troisi, Roberto I. ; Hoek, Bart van ; Valente, Umberto ; Wolf, Philippe ; Wolters, Heiner ; Mirza, Darius F. ; Scholz, Tim ; Steininger, Rudolf ; Soderdahl, Gunnar ; Strasser, Simone I. ; Jauch, Karl-Walter ; Neuhaus, Peter ; Schlitt, Hans J. ; Geissler, Edward K.
Background: The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC. Methods: The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 3-year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating. Discussion: If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from rejection, patients should experience less post-transplant problems with HCC recurrence, and therefore could expect a longer and better quality of life. A positive outcome will likely change the standard of posttransplant immunosuppressive care for LT patients with HCC. (trial registered at www.clinicaltrials.gov: NCT00355862) (EudraCT Number: 2005-005362-36)