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Andresen, Sabine ; Lips, Anna ; Möller, Renate ; Rusack, Tanja ; Schröer, Wolfgang ; Thomas, Severine ; Wilmes, Johanna
Dieses Papier präsentiert erste Ergebnisse der bundesweiten Studie JuCo – Erfahrungen und Perspektiven von jungen Menschen während der Corona-Maßnahmen. Die Befragung wurde vom Forschungsverbund "Kindheit – Jugend – Familie in der Corona-Zeit" umgesetzt, der sich aus den Universitäten Hildesheim, Frankfurt und Bielefeld zusammensetzt. Über 5.000 Jugendliche und junge Erwachsene zwischen 15 und 30 Jahren sind in die Analysen eingeflossen und zeigen auf, wie es den jungen Menschen geht und welche Botschaften sie haben.
Miethke, Marcus ; Pieroni, Marco ; Weber, Karl Tilmann ; Brönstrup, Mark ; Hammann, Peter ; Halby, Ludovic ; Arimondo, Paola B. ; Glaser, Philippe ; Aigle, Bertrand ; Bode, Helge Björn ; Moreira, Rui ; Li, Yanyan ; Luzhetskyy, Andriy ; Medema, Marnix H. ; Pernodet, Jean-Luc ; Stadler, Marc ; Tormo, José Rubén ; Genilloud, Olga ; Truman, Andrew W. ; Weissman, Kira J. ; Takano, Eriko ; Sabatini, Stefano ; Stegmann, Evi ; Brötz, Heike ; Wohlleben, Wolfgang ; Seemann, Myriam ; Empting, Martin ; Hirsch, Anna K. H. ; Loretz, Brigitta ; Lehr, Claus-Michael ; Titz, Alexander ; Herrmann, Jennifer ; Jäger, Timo ; Alt, Silke ; Hesterkamp, Thomas ; Winterhalter, Mathias ; Schiefer, Andrea ; Pfarr, Kenneth ; Hoerauf, Achim ; Graz, Heather ; Graz, Michael ; Lindvall, Mika ; Ramurthy, Savithri ; Karlén, Anders ; Dongen, Maarten van ; Petkovic, Hrvoje ; Keller, Andreas ; Peyrane, Frédéric ; Donadio, Stefano ; Fraisse, Laurent ; Piddock, Laura J. V. ; Gilbert, Ian H. ; Moser, Heinz E. ; Müller, Rolf
An ever-increasing demand for novel antimicrobials to treat life-threatening infections caused by the global spread of multidrug-resistant bacterial pathogens stands in stark contrast to the current level of investment in their development, particularly in the fields of natural-product-derived and synthetic small molecules. New agents displaying innovative chemistry and modes of action are desperately needed worldwide to tackle the public health menace posed by antimicrobial resistance. Here, our consortium presents a strategic blueprint to substantially improve our ability to discover and develop new antibiotics. We propose both short-term and long-term solutions to overcome the most urgent limitations in the various sectors of research and funding, aiming to bridge the gap between academic, industrial and political stakeholders, and to unite interdisciplinary expertise in order to efficiently fuel the translational pipeline for the benefit of future generations.
Eckert, Ellen ; Laeng, Alexandra ; Lossow, Stefan ; Kellmann, Sylvia ; Stiller, Gabriele ; Clarmann, Thomas von ; Glatthor, Norbert ; Höpfner, Michael ; Kiefer, Michael ; Oelhaf, Herman ; Orphal, Johannes ; Funke, Bernd ; Grabowski, Udo ; Haenel, Florian ; Linden, Andrea ; Wetzel, Gerald ; Woiwode, Wolfgang ; Bernath, Peter F. ; Boone, Christopher D. ; Dutton, Geoffrey S. ; Elkins, James W. ; Engel, Andreas ; Gille, John C. ; Kolonjari, Felicia ; Sugita, Takafumi ; Toon, Geoffrey C. ; Walker, Kaley A.
Profiles of CFC-11 (CCl3F) and CFC-12 (CCl2F2) of the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) aboard the European satellite Envisat have been retrieved from versions MIPAS/4.61 to MIPAS/4.62 and MIPAS/5.02 to MIPAS/5.06 level-1b data using the scientific level-2 processor run by Karlsruhe Institute of Technology (KIT), Institute of Meteorology and Climate Research (IMK) and Consejo Superior de Investigaciones Científicas (CSIC), Instituto de Astrofísica de Andalucía (IAA). These profiles have been compared to measurements taken by the balloon-borne cryosampler, Mark IV (MkIV) and MIPAS-Balloon (MIPAS-B), the airborne MIPAS-STRatospheric aircraft (MIPAS-STR), the satellite-borne Atmospheric Chemistry Experiment Fourier transform spectrometer (ACE-FTS) and the High Resolution Dynamic Limb Sounder (HIRDLS), as well as the ground-based Halocarbon and other Atmospheric Trace Species (HATS) network for the reduced spectral resolution period (RR: January 2005–April 2012) of MIPAS. ACE-FTS, MkIV and HATS also provide measurements during the high spectral resolution period (full resolution, FR: July 2002–March 2004) and were used to validate MIPAS CFC-11 and CFC-12 products during that time, as well as profiles from the Improved Limb Atmospheric Spectrometer, ILAS-II. In general, we find that MIPAS shows slightly higher values for CFC-11 at the lower end of the profiles (below ∼ 15 km) and in a comparison of HATS ground-based data and MIPAS measurements at 3 km below the tropopause. Differences range from approximately 10 to 50 pptv ( ∼ 5–20 %) during the RR period. In general, differences are slightly smaller for the FR period. An indication of a slight high bias at the lower end of the profile exists for CFC-12 as well, but this bias is far less pronounced than for CFC-11 and is not as obvious in the relative differences between MIPAS and any of the comparison instruments. Differences at the lower end of the profile (below ∼ 15 km) and in the comparison of HATS and MIPAS measurements taken at 3 km below the tropopause mainly stay within 10–50 pptv (corresponding to ∼ 2–10 % for CFC-12) for the RR and the FR period. Between ∼ 15 and 30 km, most comparisons agree within 10–20 pptv (10–20 %), apart from ILAS-II, which shows large differences above ∼ 17 km. Overall, relative differences are usually smaller for CFC-12 than for CFC-11. For both species – CFC-11 and CFC-12 – we find that differences at the lower end of the profile tend to be larger at higher latitudes than in tropical and subtropical regions. In addition, MIPAS profiles have a maximum in their mixing ratio around the tropopause, which is most obvious in tropical mean profiles. Comparisons of the standard deviation in a quiescent atmosphere (polar summer) show that only the CFC-12 FR error budget can fully explain the observed variability, while for the other products (CFC-11 FR and RR and CFC-12 RR) only two-thirds to three-quarters can be explained. Investigations regarding the temporal stability show very small negative drifts in MIPAS CFC-11 measurements. These instrument drifts vary between ∼ 1 and 3 % decade−1. For CFC-12, the drifts are also negative and close to zero up to ∼ 30 km. Above that altitude, larger drifts of up to ∼ 50 % decade−1 appear which are negative up to ∼ 35 km and positive, but of a similar magnitude, above.
Kaufmann, Manfred ; Blank, Jörg ; Guggenmoser, Tobias ; Ungermann, Jörn ; Engel, Andreas ; Ern, Manfred ; Friedl-Vallon, Felix ; Gerber, Daniel ; Grooß, Jens-Uwe ; Günther, Gebhard ; Höpfner, Michael ; Kleinert, Anne ; Latzko, Thomas ; Maucher, Guido ; Neubert, Tom ; Nordmeyer, Hans ; Oelhaf, Hermann ; Olschewski, Friedhelm ; Orphal, Johannes ; Preusse, Peter ; Schlager, Hans ; Schneider, Herbert ; Schüttemeyer, Dirk ; Stroh, Fred ; Sumińska-Ebersoldt, Olga ; Vogel, Bärbel ; Volk, C.-Michael ; Woiwode, Wolfgang ; Riese, Martin
The three-dimensional quantification of small scale processes in the upper troposphere and lower stratosphere is one of the challenges of current atmospheric research and requires the development of new measurement strategies. This work presents first results from the newly developed Gimballed Limb Observer for Radiance Imaging of the Atmosphere (GLORIA) obtained during the ESSenCe and TACTS/ESMVal aircraft campaigns. The focus of this work is on the so-called dynamics mode data characterized by a medium spectral and a very high spatial resolution. The retrieval strategy for the derivation of two- and three-dimensional constituent fields in the upper troposphere and lower stratosphere is presented. Uncertainties of the main retrieval targets (temperature, O3, HNO3 and CFC-12) and their spatial resolution are discussed. During ESSenCe, high resolution two-dimensional cross-sections have been obtained. Comparisons to collocated remote-sensing and in-situ data indicate a good agreement between the data sets. During TACTS/ESMVal a tomographic flight pattern to sense an intrusion of stratospheric air deep into the troposphere has been performed. This filament could be reconstructed with an unprecedented spatial resolution of better than 500 m vertically and 20 km × 20 km horizontally.
Kaufmann, Manfred ; Blank, Jörg ; Guggenmoser, Tobias ; Ungermann, Jörn ; Engel, Andreas ; Ern, Manfred ; Friedl-Vallon, Felix ; Gerber, Daniel ; Grooß, Jens-Uwe ; Günther, Gebhard ; Höpfner, Michael ; Kleinert, Anne ; Kretschmer, Ernst ; Latzko, Thomas ; Maucher, Guido ; Neubert, Tom ; Nordmeyer, Hans ; Oelhaf, Hermann ; Olschewski, Friedhelm ; Orphal, Johannes ; Preusse, Peter ; Schlager, Hans ; Schneider, Herbert ; Schüttemeyer, Dirk ; Stroh, Fred ; Suminska-Ebersoldt, Olga ; Vogel, Bärbel ; Volk, C.-Michael ; Woiwode, Wolfgang ; Riese, Martin
The three-dimensional quantification of small-scale processes in the upper troposphere and lower stratosphere is one of the challenges of current atmospheric research and requires the development of new measurement strategies. This work presents the first results from the newly developed Gimballed Limb Observer for Radiance Imaging of the Atmosphere (GLORIA) obtained during the ESSenCe (ESa Sounder Campaign) and TACTS/ESMVal (TACTS: Transport and composition in the upper troposphere/lowermost stratosphere, ESMVal: Earth System Model Validation) aircraft campaigns. The focus of this work is on the so-called dynamics-mode data characterized by a medium-spectral and a very-high-spatial resolution. The retrieval strategy for the derivation of two- and three-dimensional constituent fields in the upper troposphere and lower stratosphere is presented. Uncertainties of the main retrieval targets (temperature, O3, HNO3, and CFC-12) and their spatial resolution are discussed. During ESSenCe, high-resolution two-dimensional cross-sections have been obtained. Comparisons to collocated remote-sensing and in situ data indicate a good agreement between the data sets. During TACTS/ESMVal, a tomographic flight pattern to sense an intrusion of stratospheric air deep into the troposphere was performed. It was possible to reconstruct this filament at an unprecedented spatial resolution of better than 500 m vertically and 20 × 20 km horizontally.
Görlich, Nina ; Brand, Hannah Antonia ; Langhans, Valerie ; Tesch, Sebastian ; Schachtner, Thomas ; Koch, Benjamin Florian ; Paliege, Alexander ; Schneider, Wolfgang ; Grützkau, Andreas ; Reinke, Petra ; Enghard, Philipp
Creatinine and proteinuria are used to monitor kidney transplant patients. However, renal biopsies are needed to diagnose renal graft rejection. Here, we assessed whether the quantification of different urinary cells would allow non-invasive detection of rejection. Urinary cell numbers of CD4+ and CD8+ T cells, monocytes/macrophages, tubular epithelial cells (TEC), and podocalyxin(PDX)-positive cells were determined using flow cytometry and were compared to biopsy results. Urine samples of 63 renal transplant patients were analyzed. Patients with transplant rejection had higher amounts of urinary T cells than controls; however, patients who showed worsening graft function without rejection had similar numbers of T cells. T cells correlated with histological findings (interstitial inflammation p = 0.0005, r = 0.70; tubulitis p = 0.006, r = 0.58). Combining the amount of urinary T cells and TEC, or T cells and PDX+ cells, yielded a significant segregation of patients with rejection from patients without rejection (all p < 0.01, area under the curve 0.89–0.91). Urinary cell populations analyzed by flow cytometry have the potential to introduce new monitoring methods for kidney transplant patients. The combination of urinary T cells, TEC, and PDX-positive cells may allow non-invasive detection of transplant rejection.
Bärtsch, Marc-Andrea ; Mai, Elias K. ; Hielscher, Thomas ; Bertsch, Uta ; Salwender, Hans J. ; Munder, Markus ; Fuhrmann, Stephan ; Dührsen, Ulrich ; Brossart, Peter ; Neben, Kai ; Schlenzka, Jana ; Kunz, Christina ; Raab, Marc-Steffen ; Hillengaß, Jens ; Jauch, Anna ; Seckinger, Anja ; Hose, Dirk ; Luntz, Steffen ; Sonneveld, Pieter ; Lokhorst, Henk ; Martin, Hans ; Görner, Martin ; Hoffmann, Martin ; Lindemann, Hans-Walter ; Bernhard, Helga ; Blau, Igor-Wolfgang ; Scheid, Christof ; Besemer, Britta ; Weisel, Katja C. ; Hänel, Mathias ; Dürig, Jan ; Goldschmidt, Hartmut
Lenalidomide (LEN) maintenance (MT) post autologous stem cell transplantation (ASCT) is standard of care in newly diagnosed multiple myeloma (MM) but has not been compared to other agents in clinical trials. We retrospectively compared bortezomib (BTZ; n = 138) or LEN (n = 183) MT from two subsequent GMMG phase III trials. All patients received three cycles of BTZ-based triplet induction and post-ASCT MT. BTZ MT (1.3 mg/m2 i.v.) was administered every 2 weeks for 2 years. LEN MT included two consolidation cycles (25 mg p.o., days 1–21 of 28 day cycles) followed by 10–15 mg/day for 2 years. The BTZ cohort more frequently received tandem ASCT (91% vs. 33%) due to different tandem ASCT strategies. In the LEN and BTZ cohort, 43% and 46% of patients completed 2 years of MT as intended (p = 0.57). Progression-free survival (PFS; HR = 0.83, p = 0.18) and overall survival (OS; HR = 0.70, p = 0.15) did not differ significantly with LEN vs. BTZ MT. Patients with <nCR after first ASCT were assigned tandem ASCT in both trials. In patients with <nCR and tandem ASCT (LEN: n = 54 vs. BTZ: n = 84), LEN MT significantly improved PFS (HR = 0.61, p = 0.04) but not OS (HR = 0.46, p = 0.09). In conclusion, the significant PFS benefit after eliminating the impact of different tandem ASCT rates supports the current standard of LEN MT after ASCT.
Karakas, Mahir ; Hoffmann, Michael Marcus ; Vollmert, Caren ; Rothenbacher, Dietrich ; Meisinger, Christa ; Winkelmann, Bernhard Rudolf ; Khuseyinova, Natalie ; Böhm, Bernhard O. ; Illig, Thomas ; März, Winfried ; Koenig, Wolfgang
Background The role of the Fcgamma receptor IIa (FcgammaRIIa), a receptor for C-reactive protein (CRP), the classical acute phase protein, in atherosclerosis is not yet clear. We sought to investigate the association of FcgammaRIIa genotype with risk of coronary heart disease (CHD) in two large population-based samples. Methods FcgammaRIIa-R/H131 polymorphisms were determined in a population of 527 patients with a history of myocardial infarction and 527 age and gender matched controls drawn from a population-based MONICA- Augsburg survey. In the LURIC population, 2227 patients with angiographically proven CHD, defined as having at least one stenosis [greater than or equal to]50%, were compared with 1032 individuals with stenosis <50%. Results In both populations genotype frequencies of the FcgammaRIIa gene did not show a significant departure from the Hardy-Weinberg equilibrium. FcgammaRIIa R(-131)->H genotype was not independently associated with lower risk of CHD after multivariable adjustments, neither in the MONICA population (odds ratio (OR) 1.08; 95% confidence interval (CI) 0.81 to 1.44), nor in LURIC (OR 0.96; 95% CI 0.81 to 1.14). Conclusion Our results do not confirm an independent relationship between FcgammaRIIa genotypes and risk of CHD in these populations.
Miesbach, Wolfgang ; Kittler, Sabine ; Bauhofer, Artur ; Königs, Christoph ; Becker, Thomas ; Nemes, László ; Staus, Alexander ; Schüttrumpf, Jörg
Introduction: Prophylaxis with factor VIII (FVIII) concentrates in children with haemophilia A (HA) is current standard of care. The benefit of prophylactic treatment for adult HA patients is not commonly accepted.
Aim: To investigate the benefit of prophylaxis over on‐demand treatment in adult and elderly patients with severe or non‐severe HA in a real‐life setting.
Methods: Data from 163 patients comprising 1202 patient‐years were evaluated for 7.5 (±5.3) years. The effects on the annual bleeding rate (ABR, including spontaneous and traumatic bleeds) of treatment with a plasma‐derived FVIII concentrate, the patient's age and disease severity were investigated. The effect of changing the treatment from on demand to continuous prophylaxis on the patients’ ABRs was further analysed.
Results: Prophylaxis had the greatest effect on the ABRs of patients of any age with severe or non‐severe HA. The difference in ABR of all patients treated on demand (median 31.4; interquartile range (IQR) 27.6; N = 83) compared with those treated prophylactically (median 1.3; IQR 3.6; N = 122) was statistically significant (P < .05), even for patients with non‐severe HA (median 8.4; IQR 15.5; N = 11) vs median 1.5; IQR 4.2 (N = 17), P < .05). Patients, aged up to 88 years, switching from on demand to continuous prophylaxis showed the lowest median ABR (1.1; N = 51) after their regimen change.
Conclusion: Any (even low‐frequency) prophylaxis results in lower ABR than on‐demand treatment. Patients switching to prophylaxis benefitted the most, irrespective of age or HA severity. Prophylactic treatment—even tertiary—is the regimen of choice for patients of any age, including elderly patients, with severe or non‐severe HA.
Wöckel, Achim ; Festl, Jasmin ; Stüber, Tanja ; Brust, Katharina ; Stangl, Stephanie ; Heuschmann, Peter Ulrich ; Albert, Ute Susann ; Budach, Wilfried ; Follmann, Markus ; Janni, Wolfgang ; Kopp, Ina ; Kreienberg, Rolf ; Kühn, Thorsten ; Langer, Thomas ; Nothacker, Monika ; Scharl, Anton ; Schreer, Ingrid ; Link, Hartmut ; Engel, Jutta ; Fehm, Tanja ; Weis, Joachim ; Welt, Anja ; Steckelberg, Anke ; Feyer, Petra ; König, Klaus ; Hahne, Andrea ; Kreipe, Hans H. ; Knoefel, Wolfram Trudo ; Denkinger, Michael ; Brucker, Sara ; Lüftner, Diana ; Kubisch, Christian ; Gerlach, Christina ; Lebeau, Annette ; Siedentopf, Friederike ; Petersen, Cordula ; Bartsch, Hans Helge ; Schulz-Wendtland, Rüdiger ; Hahn, Markus ; Hanf, Volker ; Müller-Schimpfle, Markus ; Henscher, Ulla ; Roncarati, Renza ; Katalinic, Alexander ; Heitmann, Christoph ; Honegger, Christoph ; Paradies, Kerstin ; Bjelic-Radisic, Vesna ; Degenhardt, Friedrich ; Wenz, Frederik ; Rick, Oliver ; Hölzel, Dieter ; Zaiss, Matthias ; Kemper, Gudrun ; Budach, Volker ; Denkert, Carsten Michael ; Gerber, Bernd ; Tesch, Hans ; Hirsmüller, Susanne ; Sinn, Hans-Peter ; Dunst, Jürgen ; Münstedt, Karsten ; Bick, Ulrich ; Fallenberg, Eva ; Tholen, Reina ; Hung, Roswita ; Baumann, Freerk T. ; Beckmann, Matthias Wilhelm ; Blohmer, Jens-Uwe ; Fasching, Peter Andreas ; Lux, Michael Patrick ; Harbeck, Nadia ; Hadji, Peyman ; Hauner, Hans ; Heywang-Köbrunner, Sylvia H. ; Huober, Jens ; Hübner, Jutta ; Jackisch, Christian ; Loibl, Sibylle ; Lück, Hans-Jürgen ; Minckwitz, Gunter von ; Möbus, Volker ; Müller, Volkmar ; Nöthlings, Ute ; Schmidt, Marcus ; Schmutzler, Rita Katharina ; Schneeweiss, Andreas ; Schütz, Florian ; Stickeler, Elmar ; Thomssen, Christoph ; Untch, Michael ; Wesselmann, Simone ; Bücker, Arno ; Krockenberger, Mathias Heinric
Ziele: Das Ziel dieser offiziellen Leitlinie, die von der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG) und der Deutschen Krebsgesellschaft (DKG) publiziert und koordiniert wurde, ist es, die Früherkennung, Diagnostik, Therapie und Nachsorge des Mammakarzinoms zu optimieren.
Methoden: Der Aktualisierungsprozess der S3-Leitlinie aus 2012 basierte zum einen auf der Adaptation identifizierter Quellleitlinien und zum anderen auf Evidenzübersichten, die nach Entwicklung von PICO-(Patients/Interventions/Control/Outcome-)Fragen, systematischer Recherche in Literaturdatenbanken sowie Selektion und Bewertung der gefundenen Literatur angefertigt wurden. In den interdisziplinären Arbeitsgruppen wurden auf dieser Grundlage Vorschläge für Empfehlungen und Statements erarbeitet, die im Rahmen von strukturierten Konsensusverfahren modifiziert und graduiert wurden.
Empfehlungen: Der Teil 1 dieser Kurzversion der Leitlinie zeigt Empfehlungen zur Früherkennung, Diagnostik und Nachsorge des Mammakarzinoms: Der Stellenwert des Mammografie-Screenings wird in der aktualisierten Leitlinienversion bestätigt und bildet damit die Grundlage der Früherkennung. Neben den konventionellen Methoden der Karzinomdiagnostik wird die Computertomografie (CT) zum Staging bei höherem Rückfallrisiko empfohlen. Die Nachsorgekonzepte beinhalten Untersuchungsintervalle für die körperliche Untersuchung, Ultraschall und Mammografie, während weiterführende Gerätediagnostik und Tumormarkerbestimmungen bei der metastasierten Erkrankung Anwendung finden.
Wöckel, Achim ; Festl, Jasmin ; Stüber, Tanja ; Brust, Katharina ; Stangl, Stephanie ; Heuschmann, Peter Ulrich ; Albert, Ute Susann ; Budach, Wilfried ; Follmann, Markus ; Janni, Wolfgang ; Kopp, Ina ; Kreienberg, Rolf ; Kühn, Thorsten ; Langer, Thomas ; Nothacker, Monika ; Scharl, Anton ; Schreer, Ingrid ; Link, Hartmut ; Engel, Jutta ; Fehm, Tanja ; Weis, Joachim ; Welt, Anja ; Steckelberg, Anke ; Feyer, Petra ; König, Klaus ; Hahne, Andrea ; Kreipe, Hans H. ; Knoefel, Wolfram Trudo ; Denkinger, Michael ; Brucker, Sara ; Lüftner, Diana ; Kubisch, Christian ; Gerlach, Christina ; Lebeau, Annette ; Siedentopf, Friederike ; Petersen, Cordula ; Bartsch, Hans Helge ; Schulz-Wendtland, Rüdiger ; Hahn, Markus ; Hanf, Volker ; Müller-Schimpfle, Markus ; Henscher, Ulla ; Roncarati, Renza ; Katalinic, Alexander ; Heitmann, Christoph ; Honegger, Christoph ; Paradies, Kerstin ; Bjelic-Radisic, Vesna ; Degenhardt, Friedrich ; Wenz, Frederik ; Rick, Oliver ; Hölzel, Dieter ; Zaiss, Matthias ; Kemper, Gudrun ; Budach, Volker ; Denkert, Carsten Michael ; Gerber, Bernd ; Tesch, Hans ; Hirsmüller, Susanne ; Sinn, Hans-Peter ; Dunst, Jürgen ; Münstedt, Karsten ; Bick, Ulrich ; Fallenberg, Eva ; Tholen, Reina ; Hung, Roswita ; Baumann, Freerk T. ; Beckmann, Matthias Wilhelm ; Blohmer, Jens-Uwe ; Fasching, Peter Andreas ; Lux, Michael Patrick ; Harbeck, Nadia ; Hadji, Peyman ; Hauner, Hans ; Heywang-Köbrunner, Sylvia H. ; Huober, Jens ; Hübner, Jutta ; Jackisch, Christian ; Loibl, Sibylle ; Lück, Hans-Jürgen ; Minckwitz, Gunter von ; Möbus, Volker ; Müller, Volkmar ; Nöthlings, Ute ; Schmidt, Marcus ; Schmutzler, Rita Katharina ; Schneeweiss, Andreas ; Schütz, Florian ; Stickeler, Elmar ; Thomssen, Christoph ; Untch, Michael ; Wesselmann, Simone ; Bücker, Arno ; Krockenberger, Mathias Heinric
Purpose: The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer.
Methods: The process of updating the S3 guideline dating from 2012 was based on the adaptation of identified source guidelines which were combined with reviews of evidence compiled using PICO (Patients/Interventions/Control/Outcome) questions and the results of a systematic search of literature databases and the selection and evaluation of the identified literature. The interdisciplinary working groups took the identified materials as their starting point to develop recommendations and statements which were modified and graded in a structured consensus procedure.
Recommendations: Part 1 of this short version of the guideline presents recommendations for the screening, diagnosis and follow-up care of breast cancer. The importance of mammography for screening is confirmed in this updated version of the guideline and forms the basis for all screening. In addition to the conventional methods used to diagnose breast cancer, computed tomography (CT) is recommended for staging in women with a higher risk of recurrence. The follow-up concept includes suggested intervals between physical, ultrasound and mammography examinations, additional high-tech diagnostic procedures, and the determination of tumor markers for the evaluation of metastatic disease.
Eckert, Ellen ; Laeng, Alexandra ; Lossow, Stefan ; Kellmann, Sylvia ; Stiller, Gabriele ; Clarmann, Thomas von ; Glatthor, Norbert ; Höpfner, Michael ; Kiefer, Michael ; Oelhaf, Herman ; Orphal, Johannes ; Funke, Bernd ; Grabowski, Udo ; Haenel, Florian ; Linden, Andrea ; Wetzel, Gerald ; Woiwode, Wolfgang ; Bernath, Peter F. ; Boone, Christopher D. ; Dutton, Geoffrey S. ; Elkins, James W. ; Engel, Andreas ; Gille, John C. ; Kolonjari, Felicia ; Sugita, Takafumi ; Toon, Geoffrey C. ; Walker, Kaley A.
Profiles of CFC-11 (CCl3F) and CFC-12 (CCl2F2) of the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) aboard the European satellite Envisat have been retrieved from versions MIPAS/4.61 to MIPAS/4.62 and MIPAS/5.02 to MIPAS/5.06 level-1b data using the scientific level-2 processor run by Karlsruhe Institute of Technology (KIT), Institute of Meteorology and Climate Research (IMK) and Consejo Superior de Investigaciones Científicas (CSIC), Instituto de Astrofísica de Andalucía (IAA). These profiles have been compared to measurements taken by the balloon-borne cryosampler, Mark IV (MkIV) and MIPAS-Balloon (MIPAS-B), the airborne MIPAS-STRatospheric aircraft (MIPAS-STR), the satellite-borne Atmospheric Chemistry Experiment Fourier transform spectrometer (ACE-FTS) and the High Resolution Dynamic Limb Sounder (HIRDLS), as well as the ground-based Halocarbon and other Atmospheric Trace Species (HATS) network for the reduced spectral resolution period (RR: January 2005–April 2012) of MIPAS. ACE-FTS, MkIV and HATS also provide measurements during the high spectral resolution period (full resolution, FR: July 2002–March 2004) and were used to validate MIPAS CFC-11 and CFC-12 products during that time, as well as profiles from the Improved Limb Atmospheric Spectrometer, ILAS-II. In general, we find that MIPAS shows slightly higher values for CFC-11 at the lower end of the profiles (below ∼ 15 km) and in a comparison of HATS ground-based data and MIPAS measurements at 3 km below the tropopause. Differences range from approximately 10 to 50 pptv ( ∼ 5–20 %) during the RR period. In general, differences are slightly smaller for the FR period. An indication of a slight high bias at the lower end of the profile exists for CFC-12 as well, but this bias is far less pronounced than for CFC-11 and is not as obvious in the relative differences between MIPAS and any of the comparison instruments. Differences at the lower end of the profile (below ∼ 15 km) and in the comparison of HATS and MIPAS measurements taken at 3 km below the tropopause mainly stay within 10–50 pptv (corresponding to ∼ 2–10 % for CFC-12) for the RR and the FR period. Between ∼ 15 and 30 km, most comparisons agree within 10–20 pptv (10–20 %), apart from ILAS-II, which shows large differences above ∼ 17 km. Overall, relative differences are usually smaller for CFC-12 than for CFC-11. For both species – CFC-11 and CFC-12 – we find that differences at the lower end of the profile tend to be larger at higher latitudes than in tropical and subtropical regions. In addition, MIPAS profiles have a maximum in their mixing ratio around the tropopause, which is most obvious in tropical mean profiles. Comparisons of the standard deviation in a quiescent atmosphere (polar summer) show that only the CFC-12 FR error budget can fully explain the observed variability, while for the other products (CFC-11 FR and RR and CFC-12 RR) only two-thirds to three-quarters can be explained. Investigations regarding the temporal stability show very small negative drifts in MIPAS CFC-11 measurements. These instrument drifts vary between ∼ 1 and 3 % decade−1. For CFC-12, the drifts are also negative and close to zero up to ∼ 30 km. Above that altitude, larger drifts of up to ∼ 50 % decade−1 appear which are negative up to ∼ 35 km and positive, but of a similar magnitude, above.
Schnütgen, Frank ; Hansen, Jens ; De-Zolt, Silke ; Horn, Carsten ; Lutz, Marcus ; Floss, Thomas ; Wurst, Wolfgang ; Ruiz Noppinger, Patricia ; Melchner, Harald von
Gene trapping is used to introduce insertional mutations into genes of mouse embryonic stem cells (ESCs). It is performed with gene trap vectors that simultaneously mutate and report the expression of the endogenous gene at the site of insertion and provide a DNA tag for rapid identification of the disrupted gene. Gene traps have been employed worldwide to assemble libraries of mouse ESC lines harboring mutations in single genes, which can be used to make mutant mice. However, most of the employed gene trap vectors require gene expression for reporting a gene trap event and therefore genes that are poorly expressed may be under-represented in the existing libraries. To address this problem, we have developed a novel class of gene trap vectors that can induce gene expression at insertion sites, thereby bypassing the problem of intrinsic poor expression. We show here that the insertion of the osteopontin enhancer into several conventional gene trap vectors significantly increases the gene trapping efficiency in high-throughput screens and facilitates the recovery of poorly expressed genes.
Rodríguez Ramos, Pablo ; Chlad, Lukáš ; Epple, Eliane ; Fabbietti, Laura ; Galatyuk, Tetyana ; Golubeva, Marina ; Guber, Fedor ; Hlaváč, Stanislav ; Ivashkin, Alexander ; Kajetanowic, Marcin ; Kardan, Behruz ; Koenig, Wolfgang ; Korcyl, Grzegorz ; Kugler, Andrej ; Lapidus, Kirill ; Linev, Serguei ; Lisowski, Edward ; Neiser, Andreas ; Ott, Herwig ; Otte, Peter-Bernd ; Petukhov, Oleg ; Pietraszko, Jerzy ; Reshetin, Andrey ; Rost, Adrian ; Salabura, Piotr ; Sobolev, Yuri G. ; Svoboda, Ondřej ; Thomas, Andreas ; Tlustý, Pavel ; Traxler, Michael
Electromagnetic calorimeter (ECAL) is being developed to complement dilepton spectrometer HADES. ECAL will enable the HADES@FAIR experiment to measure data on neutral meson production in heavy ion collisions at the energy range of 2-10 AGeV on the beam of future accelerator SIS100@FAIR. We will report results of the last beam test with quasi-monoenergetic photons carried out in MAMI facility at Johannes Gutenberg Universität Mainz.
Adamczewski-Musch, Jörn ; Arnold, Oliver Werner ; Behnke, Claudia ; Belounnas, Amel ; Belyaev, Alexei V. ; Berger-Chen, Jia-Chii ; Biernat, Jacek ; Blanco, Alberto ; Blume, Christoph ; Böhmer, Michael ; Bordalo, Paula ; Chernenko, Sergey P. ; Chlad, Lukáš ; Deveaux, Christina Anna ; Dreyer, Jörg ; Dybczak, Adrian ; Epple, Eliane ; Fabbietti, Laura ; Fateev, Oleg ; Filip, Peter ; Fonte, Paulo ; Franco, Celso ; Friese, Jürgen ; Fröhlich, Ingo ; Galatyuk, Tetyana ; Garzón, Juan A. ; Gernhäuser, Roman ; Golubeva, Marina ; Greifenhagen, Robert ; Guber, Fedor ; Gumberidze, Malgorzata ; Harabasz, Szymon ; Heinz, Tobias ; Hennino, Thierry ; Hlaváč, Stanislav ; Höhne, Claudia ; Holzmann, Romain ; Ierusalimov, Alexander P. ; Ivashkin, Alexander ; Kämpfer, Burkhard ; Karavicheva, Tatiana L. ; Kardan, Behruz ; Koenig, Ilse ; Koenig, Wolfgang ; Kolb, Burkhard W. ; Korcyl, Grzegorz ; Kornakov, Georgy ; Kotte, Roland ; Kugler, Andrej ; Kunz, Tobias ; Kurepin, Alexander ; Kurilkin, Aleksey K. ; Kurilkin, Pavel ; Ladygin, Vladimir P. ; Lalik, Rafał Tomasz ; Lapidus, Kirill ; Lebedev, Alexei ; Lopes, Luis Alberto Vieira ; Lorenz, Manuel ; Mahmoud, Tariq ; Maier, Ludwig W. ; Mangiarotti, Alessio ; Markert, Jochen ; Maurus, Steffen ; Metag, Volker ; Michel, Jan ; Mihaylov, Dimitar ; Morozov, Sergey ; Müntz, Christian ; Münzer, Robert Helmut ; Naumann, Lothar ; Nowakowski, Krzysztof ; Palka, Marek ; Parpottas, Yannis ; Pechenov, Vladimir ; Pechenova, Olga ; Petukhov, Oleg ; Pietraszko, Jerzy ; Przygoda, Witold ; Ramos, Sérgio ; Ramstein, Béatrice ; Reshetin, Andrey ; Rodriguez Ramos, Pablo ; Rosier, Philippe ; Rost, Adrian ; Sadovsky, Alexander ; Salabura, Piotr ; Scheib, Timo ; Schuldes, Heidi ; Schwab, Erwin ; Scozzi, Federico ; Seck, Florian ; Sellheim, Patrick ; Selyuzhenkov, Ilya ; Siebenson, Johannes Stephan ; Silva, Luis ; Sobolev, Yuri G. ; Spataro, Stefano ; Spies, Simon ; Ströbele, Herbert ; Stroth, Joachim ; Strzempek, Paweł ; Sturm, Christian Thomas ; Svoboda, Ondřej ; Szala, Melanie ; Tlustý, Pavel ; Traxler, Michael ; Tsertos, Haralabos ; Usenko, Evgeny A. ; Wagner, Vladimir ; Wendisch, Christian ; Wiebusch, Michael ; Wirth, Joana ; Zanevsky, Yuri V. ; Zumbruch, Peter W. ; Leifels, Yvonne
We present first data on sub-threshold production of Ks0 mesons and Λ hyperons in Au+Au collisions at sNN=2.4 GeV. We observe an universal 〈Apart〉 scaling of hadrons containing strangeness, independent of their corresponding production thresholds. Comparing the yields, their 〈Apart〉 scaling, and the shapes of the rapidity and the pt spectra to state-of-the-art transport model (UrQMD, HSD, IQMD) predictions, we find that none of them can simultaneously describe these observables with reasonable χ2 values.
Ramstein, Béatrice ; Adamczewski-Musch, Jörn ; Arnold, Oliver Werner ; Atomssa, Ermias T. ; Behnke, Claudia ; Berger-Chen, Jia-Chii ; Biernat, Jacek ; Blanco, Alberto ; Blume, Christoph ; Böhmer, Michael ; Bordalo, Paula ; Chernenko, Sergey P. ; Deveaux, Christina Anna ; Dybczak, Adrian ; Epple, Eliane ; Fabbietti, Laura ; Fateev, Oleg ; Fonte, Paulo ; Franco, Celso ; Friese, Jürgen ; Fröhlich, Ingo ; Galatyuk, Tetyana ; Garzón, Juan A. ; Gill, Katharina ; Golubeva, Marina ; Guber, Fedor ; Gumberidze, Malgorzata ; Harabasz, Szymon ; Hennino, Thierry ; Hlaváč, Stanislav ; Höhne, Claudia ; Holzmann, Romain ; Ierusalimov, Alexander P. ; Ivashkin, Alexander ; Jurkovič, Martin ; Kämpfer, Burkhard ; Karavicheva, Tatiana L. ; Kardan, Behruz ; Koenig, Ilse ; Koenig, Wolfgang ; Kolb, Burkhard W. ; Korcyl, Grzegorz ; Kornakov, Georgy ; Kotte, Roland ; Krása, Antonin ; Krebs, Erik ; Kuc, Hubert ; Kugler, Andrej ; Kunz, Tobias ; Kurepin, Alexander ; Kurilkin, Aleksey K. ; Kurilkin, Pavel ; Ladygin, Vladimir P. ; Lalik, Rafał Tomasz ; Lapidus, Kirill ; Lebedev, Alexei ; Lopes, Luis Alberto Vieira ; Lorenz, Manuel ; Mahmoud, Tariq ; 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 ; Petousis, Vlasios ; Pietraszko, Jerzy ; Przygoda, Witold ; Rehnisch, Laura ; Reshetin, Andrey ; Rost, Adrian ; Rustamov, Anar ; Sadovsky, Alexander ; Salabura, Piotr ; Scheib, Timo ; Schmidt-Sommerfeld, Korbinian ; Schuldes, Heidi ; Sellheim, Patrick ; Siebenson, Johannes Stephan ; Silva, Luis ; 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 ; Wendisch, Christian ; Wirth, Joana ; Wüstenfeld, Jörn ; Zanevsky, Yuri V. ; Zumbruch, Peter W.
Adamczewski-Musch, Jörn ; Arnold, Oliver Werner ; Behnke, Claudia ; Belounnas, Amel ; Belyaev, Alexei V. ; Berger-Chen, Jia-Chii ; Biernat, Jacek ; Blanco, Alberto ; Blume, Christoph ; Böhmer, Michael ; Bordalo, Paula ; Chernenko, Sergey P. ; Chlad, Lukáš ; Deveaux, Christina Anna ; Dreyer, Jörn ; Dybczak, Adrian ; Epple, Eliane ; Fabbietti, Laura ; Fateev, Oleg ; Filip, Peter ; Fonte, Paulo ; Franco, Celso ; Friese, Jürgen ; Fröhlich, Ingo ; Galatyuk, Tetyana ; Garzón, Juan A. ; Gernhäuser, Roman ; Golubeva, Marina ; Greifenhagen, Robert ; Guber, Fedor ; Gumberidze, Malgorzata ; Harabasz, Szymon ; Heinz, Tobias ; Hennino, Thierry ; Hlaváč, Stanislav ; Höhne, Claudia ; Holzmann, Romain ; Ierusalimov, Alexander P. ; Ivashkin, Alexander ; Kämpfer, Burkhard ; Karavicheva, Tatiana L. ; Kardan, Behruz ; Koenig, Ilse ; Koenig, Wolfgang ; Kolb, Burkhard W. ; Korcyl, Grzegorz ; Kornakov, Georgy ; Kotte, Roland ; Kugler, Andrej ; Kunz, Tobias ; Kurepin, Alexander ; Kurilkin, Aleksey K. ; Kurilkin, Pavel ; Ladygin, Vladimir P. ; Lalik, Rafał Tomasz ; Lapidus, Kirill ; Lebedev, Alexei ; Lopes, Luis Alberto Vieira ; Lorenz, Manuel ; Mahmoud, Tariq ; Maier, Ludwig W. ; Mangiarotti, Alessio ; Markert, Jochen ; Matulewicz, Tomasz ; Maurus, Steffen ; Metag, Volker ; Michel, Jan ; Mihaylov, Dimitar ; Morozov, Sergey ; Müntz, Christian ; Münzer, Robert Helmut ; Naumann, Lothar ; Nowakowski, K. ; Palka, Marek ; Parpottas, Yannis ; Pechenov, Vladimir ; Pechenova, Olga ; Petukhov, Oleg ; Piasecki, Krzysztof ; Pietraszko, Jerzy ; Przygoda, Witold ; Ramos, Sérgio ; Ramstein, Béatrice ; Reshetin, Andrey ; Rodriguez Ramos, Pablo ; Rosier, Philippe ; Rost, Adrian ; Sadovsky, Alexander ; Salabura, Piotr ; Scheib, Timo ; Schuldes, Heidi ; Schwab, Erwin ; Scozzi, Federico ; Seck, Florian ; Sellheim, Patrick ; Selyuzhenkov, Ilya ; Siebenson, Johannes Stephan ; Silva, Luis ; Sobolev, Yuri G. ; Spataro, Stefano ; Spies, Simon ; Ströbele, Herbert ; Stroth, Joachim ; Strzempek, Paweł ; Sturm, Christian Thomas ; Svoboda, Ondřej ; Szala, Melanie ; Tlustý, Pavel ; Traxler, Michael ; Tsertos, Haralabos ; Usenko, Evgeny A. ; Wagner, Vladimir ; Wendisch, Christian ; Wiebusch, Michael ; Wirth, Joana ; Wójcik, Daniel Krzysztof ; Zanevsky, Yuri V. ; Zumbruch, Peter W.
We investigate identical pion HBT intensity interferometry in central Au+Au collisions at 1.23A GeV. High-statistics π−π− and π+π+ data are measured with HADES at SIS18/GSI. The radius parameters, derived from the correlation function depending on relative momenta in the longitudinally comoving system and parametrized as three-dimensional Gaussian distribution, are studied as function of transverse momentum. A substantial charge-sign difference of the source radii is found, particularly pronounced at low transverse momentum. The extracted source parameters agree well with a smooth extrapolation of the center-of-mass energy dependence established at higher energies, extending the corresponding excitation functions down towards a very low energy.
Przygoda, Witold ; Adamczewski-Musch, Jörn ; Arnold, Oliver Werner ; Atomssa, Ermias T. ; Behnke, Claudia ; Berger-Chen, Jia-Chii ; Biernat, Jacek ; Blanco, Alberto ; Blume, Christoph ; Böhmer, Michael ; Bordalo, Paula ; Chernenko, Sergey P. ; Deveaux, Christina Anna ; Dybczak, Adrian ; Epple, Eliane ; Fabbietti, Laura ; Fateev, Oleg ; Fonte, Paulo ; Franco, Celso ; Friese, Jürgen ; Fröhlich, Ingo ; Galatyuk, Tetyana ; Garzón, Juan A. ; Gill, Katharina ; Golubeva, Marina ; Guber, Fedor ; Gumberidze, Malgorzata ; Harabasz, Szymon ; Hennino, Thierry ; Hlaváč, Stanislav ; Höhne, Claudia ; Holzmann, Romain ; Ierusalimov, Alexander P. ; Ivashkin, Alexander ; Jurkovič, Martin ; Kämpfer, Burkhard ; Karavicheva, Tatiana L. ; Kardan, Behruz ; Koenig, Ilse ; Koenig, Wolfgang ; Kolb, Burkhard W. ; Korcyl, Grzegorz ; Kornakov, Georgy ; Kotte, Roland ; Krása, Antonin ; Krebs, Erik ; Kuc, Hubert ; Kugler, Andrej ; Kunz, Tobias ; Kurepin, Alexander ; Kurilkin, Aleksey K. ; Kurilkin, Pavel ; Ladygin, Vladimir P. ; Lalik, Rafał Tomasz ; Lapidus, Kirill ; Lebedev, Alexei ; Lopes, Luis Alberto Vieira ; Lorenz, Manuel ; Mahmoud, Tariq ; 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 ; Petousis, Vlasios ; Pietraszko, Jerzy ; Ramstein, Béatrice ; Rehnisch, Laura ; Reshetin, Andrey ; Rost, Adrian ; Rustamov, Anar ; Sadovsky, Alexander ; Salabura, Piotr ; Scheib, Timo ; Schmidt-Sommerfeld, Korbinian ; Schuldes, Heidi ; Sellheim, Patrick ; Siebenson, Johannes Stephan ; Silva, Luis ; 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 ; Wendisch, Christian ; Wirth, Joana ; Wüstenfeld, Jörn ; Zanevsky, Yuri V. ; Zumbruch, Peter W.
n this paper we report on the investigation of baryonic resonance production in proton-proton collisions at the kinetic energies of 1.25 GeV and 3.5 GeV, based on data measured with HADES. Exclusive channels npπ+ and ppπ0 as well as ppe+e− were studied simultaneously in the framework of a one-boson exchange model. The resonance cross sections were determined from the one-pion channels for Δ(1232) and N(1440) (1.25 GeV) as well as further Δ and N* resonances up to 2 GeV/c2 for the 3.5 GeV data. The data at 1.25 GeV energy were also analysed within the framework of the partial wave analysis together with the set of several other measurements at lower energies. The obtained solutions provided the evolution of resonance production with the beam energy, showing a sizeable non-resonant contribution but with still dominating contribution of Δ(1232)P33. In the case of 3.5 GeV data, the study of the ppe+e− channel gave the insight on the Dalitz decays of the baryon resonances and, in particular, on the electromagnetic transition form-factors in the time-like region. We show that the assumption of a constant electromagnetic transition form-factors leads to underestimation of the yield in the dielectron invariant mass spectrum below the vector mesons pole. On the other hand, a comparison with various transport models shows the important role of intermediate ρ production, though with a large model dependency. The exclusive channels analysis done by the HADES collaboration provides new stringent restrictions on the parameterizations used in the models.
Epple, Eliane ; Adamczewski-Musch, Jörn ; Arnold, Oliver Werner ; Atomssa, Ermias T. ; Behnke, Claudia ; Berger-Chen, Jia-Chii ; Biernat, Jacek ; Blanco, Alberto ; Blume, Christoph ; Böhmer, Michael ; Bordalo, Paula ; Chernenko, Sergey P. ; Deveaux, Christina Anna ; Dybczak, Adrian ; Fabbietti, Laura ; Fateev, Oleg ; Fonte, Paulo ; Franco, Celso ; Friese, Jürgen ; Fröhlich, Ingo ; Galatyuk, Tetyana ; Garzón, Juan A. ; Gill, Katharina ; Golubeva, Marina ; Guber, Fedor ; Gumberidze, Malgorzata ; Harabasz, Szymon ; Hennino, Thierry ; Hlaváč, Stanislav ; Höhne, Claudia ; Holzmann, Romain ; Ierusalimov, Alexander P. ; Ivashkin, Alexander ; Jurkovič, Martin ; Kämpfer, Burkhard ; Karavicheva, Tatiana L. ; Kardan, Behruz ; Koenig, Ilse ; Koenig, Wolfgang ; Kolb, Burkhard W. ; Korcyl, Grzegorz ; Kornakov, Georgy ; Kotte, Roland ; Krása, Antonin ; Krebs, Erik ; Kuc, Hubert ; Kugler, Andrej ; Kunz, Tobias ; Kurepin, Alexander ; Kurilkin, Aleksey K. ; Kurilkin, Pavel ; Ladygin, Vladimir P. ; Lalik, Rafał Tomasz ; Lapidus, Kirill ; Lebedev, Alexei ; Lopes, Luis Alberto Vieira ; Lorenz, Manuel ; Mahmoud, Tariq ; 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 ; Petousis, Vlasios ; Pietraszko, Jerzy ; Przygoda, Witold ; Ramstein, Béatrice ; Rehnisch, Laura ; Reshetin, Andrey ; Rost, Adrian ; Rustamov, Anar ; Sadovsky, Alexander ; Salabura, Piotr ; Scheib, Timo ; Schmidt-Sommerfeld, Korbinian ; Schuldes, Heidi ; Sellheim, Patrick ; Siebenson, Johannes Stephan ; Silva, Luis ; 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 ; Wendisch, Christian ; Wirth, Joana ; Wüstenfeld, Jörn ; Zanevsky, Yuri V. ; Zumbruch, Peter W.
his contribution aims to give a basic overview of the latest results regarding the production of resonances in different collision systems. The results were extracted from experimental data collected with HADES that is a multipurpose detector located at the GSI Helmholtzzentrum, Darmstadt. The main points discussed here are: the properties of the strange resonances Λ(1405) and Σ(1385), the role of Δ’s as a source of pions in the final state, the production dynamics reflected in form of differential cross sections, and the role of the ϕ meson as a source for K− particles.
Entling, Martin H. ; Schweiger, Oliver ; Bacher, Sven ; Espadaler, Xavier ; Hickler, Thomas ; Kumschick, Sabrina ; Woodcock, Ben A. ; Nentwig, Wolfgang
We study how species richness of arthropods relates to theories concerning net primary productivity, ambient energy, water-energy dynamics and spatial environmental heterogeneity. We use two datasets of arthropod richness with similar spatial extents (Scandinavia to Mediterranean), but contrasting spatial grain (local habitat and country). Samples of ground-dwelling spiders, beetles, bugs and ants were collected from 32 paired habitats at 16 locations across Europe. Species richness of these taxonomic groups was also determined for 25 European countries based on the Fauna Europaea database. We tested effects of net primary productivity (NPP), annual mean temperature (T), annual rainfall (R) and potential evapotranspiration of the coldest month (PETmin) on species richness and turnover. Spatial environmental heterogeneity within countries was considered by including the ranges of NPP, T, R and PETmin. At the local habitat grain, relationships between species richness and environmental variables differed strongly between taxa and trophic groups. However, species turnover across locations was strongly correlated with differences in T. At the country grain, species richness was significantly correlated with environmental variables from all four theories. In particular, species richness within countries increased strongly with spatial heterogeneity in T. The importance of spatial heterogeneity in T for both species turnover across locations and for species richness within countries suggests that the temperature niche is an important determinant of arthropod diversity. We suggest that, unless climatic heterogeneity is constant across sampling units, coarse-grained studies should always account for environmental heterogeneity as a predictor of arthropod species richness, just as studies with variable area of sampling units routinely consider area.
Hohenforst-Schmidt, Wolfgang ; Zarogoulidis, Paul ; Stopek, Joshua ; Kosmidis, Efstratios ; Vogl, Thomas J. ; Linsmeier, Bernd ; Tsakiridis, Kosmas ; Lampaki, Sofia ; Lazaridis, George ; Mpakas, Andreas ; Browning, Robert ; Papaiwannou, Antonis ; Drevelegas, Antonis ; Baka, Sofia ; Karavasilis, Vasilis ; Mpoukovinas, Ioannis ; Turner, J. Francis ; Zarogoulidis, Konstantinos ; Brachmann, Johannes
Novel therapies for lung cancer are being explored nowadays with local therapies being the tip of the arrow. Intratumoral chemotherapy administration and local microwave ablation have been investigated in several studies. It has been previously proposed that lipiodol has the ability to modify the microenvironment matrix. In our current study we investigated this theory in BALBC mice. In total 160 BALBC mice were divided in eight groups: a) control, b) cisplatin, c) microwave, d) microwave and lipiodol, e) cisplatin and lipiodol, f) microwave and cisplatin, g) lipiodol and h) lipiodol, cisplatin and microwave. Lewis lung carcinoma cell lines (106) were injected into the right back leg of each mouse. After the 8th day, when the tumor volume was about 100mm3 the therapy application was initiated, once per week for four weeks. Magnetic resonance imaging was performed for each tumor when a mouse died or when sacrificed if they were still alive by the end of the experiment (8-Canal multifunctional spool; NORAS MRI products, Gmbh, Germany). Imaging and survival revealed efficient tumor apoptosis for the groups b,c,d,e and f. However; severe toxicity was observed in group h and no follow up was available for this group after the second week of therapy administration. Lipiodol in its current form does assist in a more efficient way the distribution of cisplatin, as the microwave apoptotic effect. Future modification of lipiodol might provide a more efficient method of therapy enhancement. Combination of drug and microwave ablation is possible and has an efficient apoptotic effect.
Buchbesprechungen
(2014)
Mahn, Detlef ; Mika, Marleen ; Starke-Ottich, Indra ; Ehmke, Wolfgang ; Baumann, Kurt ; Gregor, Thomas ; Stich, Koloman ; Walther, Franziska
Es werden folgende Publikation rezensiert: Baumbach & Pfützenreuter: Steppenlebensräume Europas, Beil et al.: Die Sand-Silberscharte in Hessen, Bönsel et al.: Naturschätze in Gießen, Bönsel et al.: Von Venuskamm, Finkensame und Hasenohr, Bönsel et al.: Die Pflanzenwelt im Westerwald, Hodvina: Die Pflanzenaquarelle des Emil Pfeiffer, Jenrich et al.: Das Rote Moor, Lange: Blütenzauber, Magistrat der Stadt Offenbach am Main: Lebensräume und Artenvielfalt in Offenbach, Schmidt & Meyer: Hessische Naturwaldreservate im Portrait: Kinzigaue.
Jedmowski, Christoph ; Ashoub, Ahmed ; Beckhaus, Tobias ; Berberich, Thomas ; Karas, Michael ; Brüggemann, Wolfgang
The adaptive response of Sorghum bicolor landraces from Egypt to drought stress and following recovery was analyzed using two-dimensional difference gel electrophoresis, 2D-DIGE. Physiological measurements and proteome alterations of accession number 11434, drought tolerant, and accession number 11431, drought sensitive, were compared to their relative control values after drought stress and following recovery. Differentially expressed proteins were analysed by Matrix assisted laser desorption ionisation time-of-flight mass spectrometry, MALDI-TOF-MS. Alterations in protein contents related to the energy balance, metabolism (sensu Mewes et al. 1997), and chaperons were the most apparent features to elucidate the differences between the drought tolerant and sensitive accessions. Further alterations in the levels of proteins related to transcription and protein synthesis are discussed.
Boehme, Stephanie ; Ritter, Viktoria ; Tefikow, Susan ; Stangier, Ulrich ; Strauß, Bernhard ; Miltner, Wolfgang H. R. ; Straube, Thomas
Disorder-relevant but task-unrelated stimuli impair cognitive performance in social anxiety disorder (SAD); however, time course and neural correlates of emotional interference are unknown. The present study investigated time course and neural basis of emotional interference in SAD using event-related functional magnetic resonance imaging (fMRI). Patients with SAD and healthy controls performed an emotional stroop task which allowed examining interference effects on the current and the succeeding trial. Reaction time data showed an emotional interference effect in the current trial, but not the succeeding trial, specifically in SAD. FMRI data showed greater activation in the left amygdala, bilateral insula, medial prefrontal cortex (mPFC), dorsal anterior cingulate cortex (ACC), and left opercular part of the inferior frontal gyrus during emotional interference of the current trial in SAD patients. Furthermore, we found a positive correlation between patients’ interference scores and activation in the mPFC, dorsal ACC and left angular/supramarginal gyrus. Taken together, results indicate a network of brain regions comprising amygdala, insula, mPFC, ACC, and areas strongly involved in language processing during the processing of task-unrelated threat in SAD. However, specifically the activation in mPFC, dorsal ACC, and left angular/supramarginal gyrus is associated with the strength of the interference effect, suggesting a cognitive network model of attentional bias in SAD. This probably comprises exceeded allocation of attentional resources to disorder-related information of the presented stimuli and increased self-referential and semantic processing of threat words in SAD.
Mander, Johannes ; Blanck, Paul ; Neubauer, Andreas B. ; Kröger, Paula ; Flückiger, Christoph ; Lutz, Wolfgang ; Barnow, Sven ; Bents, Hinrich ; Heidenreich, Thomas
OBJECTIVE: There is scarce research on the effects of mindfulness in individual therapy. As many practitioners integrate mindfulness exercises into individual therapy, empirical evidence is of high clinical relevance.
METHOD: We investigated the effects of a session-introducing intervention with mindfulness elements (SIIME) in a randomized, controlled design. The effects of SIIME on therapeutic alliance and symptomatic outcome were compared with progressive muscle relaxation (PMR) and treatment-as-usual (TAU) control conditions. The sample comprised 162 patients with anxiety and depression.
RESULTS: Multilevel modeling revealed a significant symptom reduction and significant increase of alliance over the course of therapy. There were no significant time-condition interactions on outcome and alliance, indicating the comparable efficiency of all three treatment conditions.
CONCLUSIONS: We found no advantage of SIIME versus PMR and TAU. Add-on mindfulness might not improve individual therapy related to alliance and outcome.
Rezensionen [2019]
(2019)
Schmidt, David N. ; Vishek, Svetlana ; Blumesberger, Susanne ; Bitterlich, Thomas ; König, Nicola ; Seifert, Martina ; Franz, Kurt ; Loidl, Sonja ; Seibert, Ernst ; Stierstorfer, Michael ; Kliewer, Annette ; Schäfer, Iris ; Janka, Markus ; Hoffmann, Lena ; Biesterfeld, Wolfgang ; Schulz, Farriba ; Lexe, Heidi ; Franz, Kurt ; Bieker, Nadine ; Sarvari, Lukas ; Egerer, Katharina ; Vollbrecht, Ralf ; Riegler, Susanne ; Schmerheim, Philipp ; Becker, Karina ; Müller-Carstens, Sonja
Verzeichnis
Einzelrezensionen
163 Babenhauserheide, Melanie: Harry Potter und die Widersprüche der Kulturindustrie. Eine ideologiekritische Analyse (DAVID N. SCHMIDT)
165 Ballis, Anja/Pecher, Claudia Maria/ Schuler, Rebecca (Hrsg.): Mehrsprachige Kinder- und Jugendliteratur. Überlegungen zur Systematik, Didaktik und Verbreitung (SVETLANA VISHEK)
167 Bannasch, Bettina/Matthes, Eva (Hrsg.): Kinder- und Jugendliteratur. Historische, erzähl- und medientheoretische, pädagogische und therapeutische Perspektiven (susanne blumesberger)
169 Batzke, Ina/ Erbacher, Eric C. /Heß, Linda M. / Lenhardt, Corinna (Hrsg.): Exploring the Fantastic. Genre, Ideology, and Popular Culture (THOMAS BITTERLICH)
170 Bertling, Maria: All-Age-Literatur. Die Entdeckung einer neuen Zielgruppe und ihrer Rezeptionsmodalitäten (NICOLA KÖNIG)
172 Blümer, Agnes: Mehrdeutigkeit übersetzen. Englische und französische Kinderliteraturklassiker der Nachkriegszeit in deutscher Übertrag (MARTINA SEIFERT)
174 Blumesberger, Susanne/Thunecke, Jörg (Hrsg.): Deutschsprachige Kinder- und Jugendliteratur während der Zwischenkriegszeit und im Exil. Schwerpunkt Österreich (KURT FRANZ)
176 Busch, Nathanael /Velten, Hans Rudolf (Hrsg.): Die Literatur des Mittelalters im Fantasyroman (SONJA LOIDL)
178 Cave, Roderick/Ayad, Sara (Hrsg.): Die Geschichte des Kinderbuches in 100 Büchern (ERNST SEIBERT)
180 Dettmar, Ute/Pecher, Claudia Maria/Schlesinger, Ron (Hrsg.): Märchen im Medienwechsel. Zur Geschichte und Gegenwart des Märchenfilms (MICHAEL STIERSTORFER)
182 Dommermuth, Clarissa: Wir sind dagegen – denn ihr seid dafür. Zur Tradition literarischer Jugendbewegungen im deutschsprachigen Raum (SUSANNE BLUMESBERGER)
184 Ellerbach, Benoît: L’Arabie contée aux Allemands. Fictions interculturelles chez Rafik Schami (ANNETTE KLIEWER)
185 Enklaar, Jattie/ Ester, Hans /Tax, Evelyne (Hrsg.): Studien über Kinder- und Jugendliteratur im europäischen Austausch von 1800 bis heute (IRIS SCHÄFER)
187 Ewers, Hans-Heino: Michael Ende neu entdecken. Was »Jim Knopf«,»Momo« und »Die unendliche Geschichte« Erwachsenen zu sagen haben (MARKUS JANKA)
189 Flegel, Monica/Parkes, Christopher (Hrsg.): Cruel Children in Popular Texts and Cultures (LENA HOFFMANN)
191 Garbe, Christine/Gürth, Christina et al. (Hrsg.): Attraktive Lesestoffe (nicht nur) für Jungen. Erzählmuster und Beispielanalysen zu populärer Kinder- und Jugendliteratur (THOMAS BITTERLICH)
193 Goga, Nina/Kümmerling-Meibauer, Bettina (Hrsg.): Maps and Mapping in Children’s Literature. Landscapes, Seascapes, and Cityscapes (Wolfgang Biesterfeld)
195 Hamer, Naomi /Nodelman, Perry / Reimer, Mavis (Hrsg.): More Words about Pictures. Current Research on Picturebooks and Visual/Verbal Texts for Young People (FARRIBA SCHULZ)
196 Hoffmann, Lena: Crossover. Mehrfachadressierung in Text, Markt und Diskurs (HEIDI LEXE)
198 Josting, Petra/Reuter, Frank/Roeder, Caroline/Wolters, Ute (Hrsg.): »Denn sie rauben sehr geschwind jedes böse Gassenkind.« ›Zigeuner‹-Bilder in Kinder- und Jugendmedien (KURT FRANZ)
200 Langemeyer, Peter /Knutsen, Karen Patrick (Hrsg.): Narratology Plus. Studies in Recent International Narratives for Children and
Young Adults / Narratologie Plus. Studien zur Erzählweise in aktueller internationaler Kinder- und Jugendliteratur (NADINE BIEKER)
202 Museumsinsel Lüttenheid (Hrsg.): Rudolf Dirks. Zwei Lausbuben und die Erfindung des modernen Comics (LUKAS SARVARI)
204 Oeste, Bettina/Preußer, Ulrike (Hrsg.): Neuvermessung deutschsprachiger Erinnerungsstrategien in der Kinder- und Jugendliteratur nach 1990 (annette kliewer)
206 Planka, Sabine (Hrsg.): Berlin. Bilder einer Metropole in erzählenden Medien für Kinder und Jugendliche (KATHARINA EGERER)
208 Press, Alexander: Die Bilder des Comics. Funktionsweisen aus kunst- und bildwissenschaftlicher Perspektive (RALF VOLLBRECHT)
209 Schenk, Klaus /Zeisberg, Ingold (Hrsg.): Fremde Räume. Interkulturalität und Semiotik des Phantastischen (ANNETTE KLIEWER)
211 Schweizerisches Institut für Kinder- und Jugendmedien SIKJM (Hrsg.): Atlas der Schweizer Kinderliteratur. Expeditionen und
Panoramen (SUSANNE RIEGLER)
Sammelrezensionen
213 Heinemann, Caroline: Produktionsräume im zeitgenössischen Kinder- und Jugendtheater. – Hentschel, Ingrid: Theater zwischen Ich und Welt. Beiträge zur Ästhetik des Kinder- und Jugendtheaters. Theorien – Praxis – Geschichte (PHILIPP SCHMERHEIM)
215 Janka, Marcus /Stierstorfer, Michael (Hrsg.): Verjüngte Antike. Griechisch-römische Mythologie in zeitgenössischen Kinder- und Jugendmedien. – Stierstorfer, Michael: Antike Mythologie in der Kinder- und Jugendliteratur der Gegenwart. Unsterbliche Götter- und Heldengeschichten? (KARINA BECKER)
218 Josting, Petra/Kruse, Iris (Hrsg.): Paul Maar. Bielefelder Poet in Residence 2015 | Paderborner Kinderliteraturtage 2016. – Wicke, Andreas /Roßbach, Nikola (Hrsg.): Paul Maar. Studien zum kinder- und jugendliterarischen Werk (SONJA MÜLLER-CARSTENS)
Es wird über die Auswertung des Notizbuches des Wiesbadener Lehrers und Botanikers Robert Zincke berichtet. Er hat darin von 1933 bis 1970 auf 285 Exkursionen zahlreiche Fundorte überwiegend in der Umgebung von Wiesbaden teilweise mit Kärtchen festgehalten. Die Funde beinhalten zahlreiche Taxa, die heute gefährdet oder ausgestorben sind.
Hollenbach, Marcus ; Prettin, Christiane ; Gundling, Felix ; Schepp, Wolfgang ; Seufert, Jochen ; Stein, Jürgen ; Rösch, Thomas ; Aberle, Jens ; Feisthammel, Jürgen ; Petrof, David ; Hoffmeister, Albrecht
Background: Obesity is a global problem leading to reduced life expectancy, cardiovascular diseases, diabetes and many types of cancer. Even people willing to accept treatment only achieve a mean weight loss of about 5 kg using commercial weight loss programs. Surgical interventions, e.g. sleeve gastrectomy or gastric bypass are effective but accompanied by risk of serious complications and side effects. Less invasive endoscopic procedures mainly comprise the intragastric balloon (IB) and the duodenal-jejunal bypass liner (DJBL). To date, a randomized comparison between these devices has not been undertaken or shown to be superior to a sham procedure.
Methods: We designed a multi-center, randomized, patient and assessor-blinded, controlled trial comparing weight loss in endoscopically implanted IB vs. DJBL vs. a sham procedure. A total of 150 patients with a BMI > 35 kg/m2 or > 30 with obesity-related comorbidities and indication for proton pump inhibitors are randomized to receive either IB, DJBL or a sham gastroscopy (2:2:1 ratio). All participants undergo regular dietary consultation. The IB will be removed after 6 months, whereas the DJBL will be explanted after 12 months. All patients will receive gastroscopies at implantation and explantation of the devices or sedation without gastroscopy to maintain blinding. Main exclusion criteria are malignant diseases, peptic ulcer or previous bariatric intervention. Weight loss 12 months after explantation of the devices, changes in comorbidities, quality of life, complication rates and safety will be evaluated.
Discussion: This trial could help to identify the most effective and safest endoscopic device, thus determining the new standard procedure for endoscopic bariatric treatment.
Trial registration: 16th January 2017. DRKS00011036. Funded by the German Research Foundation (DFG).
Rabin, Sam S. ; Melton, Joe R. ; Lasslop, Gitta ; Bachelet, Dominique ; Forrest, Matthew ; Hantson, Stijn ; Kaplan, Jed O. ; Li, Fang ; Mangeon, Stephane ; Ward, Daniel S. ; Yue, Chao ; Arora, Vivek ; Hickler, Thomas ; Kloster, Silvia ; Knorr, Wolfgang ; Nieradzik, Lars ; Spessa, Allan ; Folberth, Gerd A. ; Sheehan, Tim ; Voulgarakis, Apostolos ; Kelley, Douglas I. ; Prentice, I. Colin ; Sitch, Stephen ; Harrison, Sandy P. ; Arneth, Almut
The important role of fire in regulating vegetation community composition and contributions to emissions of greenhouse gases and aerosols make it a critical component of dynamic global vegetation models and Earth system models. Over 2 decades of development, a wide variety of model structures and mechanisms have been designed and incorporated into global fire models, which have been linked to different vegetation models. However, there has not yet been a systematic examination of how these different strategies contribute to model performance. Here we describe the structure of the first phase of the Fire Model Intercomparison Project (FireMIP), which for the first time seeks to systematically compare a number of models. By combining a standardized set of input data and model experiments with a rigorous comparison of model outputs to each other and to observations, we will improve the understanding of what drives vegetation fire, how it can best be simulated, and what new or improved observational data could allow better constraints on model behavior. In this paper, we introduce the fire models used in the first phase of FireMIP, the simulation protocols applied, and the benchmarking system used to evaluate the models. We have also created supplementary tables that describe, in thorough mathematical detail, the structure of each model.
The Fire Modeling Intercomparison Project (FireMIP), phase 1: experimental and analytical protocols
(2016)
Rabin, Sam S. ; Melton, Joe R. ; Lasslop, Gitta ; Bachelet, Dominique ; Forrest, Matthew ; Hantson, Stijn ; Li, Fang ; Mangeon, Stephane ; Yue, Chao ; Arora, Vivek ; Hickler, Thomas ; Kloster, Silvia ; Knorr, Wolfgang ; Nieradzik, Lars ; Spessa, Allan ; Folberth, Gerd A. ; Sheehan, Tim ; Voulgarakis, Apostolos ; Prentice, I. Colin ; Sitch, Stephen ; Kaplan, Jed O. ; Harrison, Sandy P. ; Arneth, Almut
The important role of fire in regulating vegetation community composition and contributions to emissions of greenhouse gases and aerosols make it a critical component of dynamic global vegetation models and Earth system models. Over two decades of development, a wide variety of model structures and mechanisms have been designed and incorporated into global fire models, which have been linked to different vegetation models. However, there has not yet been a systematic examination of how these different strategies contribute to model performance. Here we describe the structure of the first phase of the Fire Model Intercomparison Project (FireMIP), which for the first time seeks to systematically compare a number of models. By combining a standardized set of input data and model experiments with a rigorous comparison of model outputs to each other and to observations, we will improve the understanding of what drives vegetation fire, how it can best be simulated, and what new or improved observational data could allow better constraints on model behavior. Here we introduce the fire models used in the first phase of FireMIP, the simulation protocols applied, and the benchmarking system used to evaluate the models. The works published in this journal are distributed under the Creative Commons Attribution 3.0 License. This license does not affect the Crown copy-right work, which is re-usable under the Open Government Licence (OGL). The Creative Commons Attribution 3.0 License and the OGL are interoperable and do not conflict with, reduce, or limit each other.
In den Jahren 1998-2001 wurden im südwestlichen Harzvorland in Windwurfgebieten auf Unterem Buntsandstein vegetationsökologische und gehölzkundliche Erhebungen auf Dauerflächen durchgeführt, um die Sukzessionsdynamik und Regeneration gestörter Buchenwälder (Galio odorati-Fagetum, Luzulo-Fagetum) in Abhängigkeit von ehemaliger Nutzungsgeschichte, aktueller forstlicher (Nicht-) Behandlung und Störungsflächengröße zu studieren. Im vierten Jahr nach dem 1997er Sturm wird das Bild in allen großflächig geworfenen Bestandesteilen durch ausgedehnte Pionierstrauchfluren bestimmt (hauptsächlich Rubus idaeus, ferner auch Sambucus racemosa, S. nigra und Rubus fruticosus agg.), während Pionierbaumarten weitestgehend fehlen. In allen Untersuchungsflächen steigen die Artenzahlen bis zum vierten Jahr nach dem Sturm an. Unter der üppig entwickelten Strauchschicht ist ein Überdauern laubwaldtypischer Querco-Fagetea-Arten und damit von Frische- und Schattenzeigern zu beobachten und auch in Zukunft wahrscheinlich. Ruderalfluren (v.a. mit Artemisietea-Arten) stellten nur ein kurzfristiges Zwischenstadium dar. Obwohl sich die Flächen im bisherigen Sukzessionsverlauf angleichen, sind anfangs noch deutliche Unterschiede zwischen dem etwa 30 Jahre ungenutzten Naturwald Königsbuche und den bewirtschafteten Wäldern ersichtlich. Dies zeigt sich beim Naturwald u.a. in relativ geringen Artenzahlen sowie geringen Abundanzanteilen an Epilobietea-Arten, Sträuchern, Licht- und Stickstoffzeigern. Damit bestätigen sich Erkenntnisse aus Vergleichsuntersuchungen von nicht geworfenen Natur- und Wirtschaftswäldern in der Optimalphase. Im Unterschied zu geräumten Flächen zeichnen sich belassene Flächen u.a. durch eine geringere Artenzahl sowie vergleichsweise hohe Abundanzanteile an Krautigen und Arten mit temporärer bis kurzfristiger Samenbank aus. Die Störungsflächengröße hat ebenfalls einen großen Einfluss auf den Sukzessionsverlauf. Mit zunehmender Ausdehnung der gestörten Fläche und abnehmender Überschirmung steigt die Artenzahl immer stärker an. Gleichzeitig wird eine Veränderung hin zu waldfremden Sukzessionstadien deutlicher. Die Klimaxbaumart Buche behält in der Naturverjüngung zwar die Dominanz, verliert mit zunehmender Störungsflächengröße aber Anteile am Baumartenspektrum und weist stark sinkende Sämlingszahlen auf, vermutlich bedingt durch die Konkurrenz der Pionierstrauchfluren. Während in Windwurflücken die Waldregeneration hin zur standortstypischen Buchenwaldgesellschaft unmittelbar gewährleistet ist, wird sie bei Flächenwurf längere Zeit in Anspruch nehmen. Hierin besteht ein wesentlicher Unterschied zu benachbarten Buchen-Windwürfen auf basenreichen Standorten (z.B. Hainholz bei Osterode), wo die Waldregeneration unabhängig von der Störungsflächengröße ohne Pionierstadien sehr schnell voranschreitet. Dies könnte in zukünftigen Waldbaukonzepten für vergleichbare Windwurfsituationen berücksichtigt werden, indem eine Wiederaufforstung nur noch bei entsprechend ungünstigen Verjüngungsvorräten notwendig wird. Es finden sich bisher keine Hinweise auf einen Artenwechsel, wie er z.B. von REMMERT (1985, 1987, 1991) im Mosaik-Zyklus-Konzept postuliert wurde. Eher sollte von einer zwischenzeitlichen Überlagerung der ursprünglichen Vegetation gesprochen werden, die von Standort und Störungsflächengröße abhängig ist und eine teilweise massive Verschiebung in den Dominanzverhältnissen der Waldarten mit einschliesst.
Cardiovascular diseases account for more than half of total mortality before the age of 75 in industrialized countries. To develop therapies promoting the compensatory growth of blood vessels could be superior to palliative surgical surgical interventions. Therefore, much effort has been put into investigating underlying mechanisms. Depending on the initial trigger, growth of blood vessels in adult organisms proceeds via two major processes, angiogenesis and arteriogenesis. While angiogenesis is induced by hypoxia and results in new capillaries, arteriogenesis is induced by physical forces, most importantly fluid shear stress. Consequently, chronically elevated fluid shear stress was found to be the strongest trigger under experimental conditions. Arteriogenesis describes the remodelling of pre-existing arterio-arteriolar anastomoses to completely developed and functional arteries. In both growth processes, enlargement of vascular wall structures was proposed to be covered by proliferation of existing wall cells. Recently, increasing evidence emerges, implicating a pivotal role for circulating cells, above all blood monocytes, in vascular growth processes. Since it has been shown that monocytes/macrophage release a cocktail of chemokines, growth factors and proteases involved in vascular growth, their contribution seems to be of a paracrine fashion. A similar role is currently discussed for various populations of bone-marrow derived stem cells and endothelial progenitors. In contrast, the initial hypothesis that these cells -after undergoing a (trans-)differentiation- contribute by a structural integration into the growing vessel wall, is increasingly challenged.
Troidl, Kerstin ; Schubert, Christian ; Vlacil, Ann-Kathrin ; Chennupati, Ramesh ; Koch, Sören ; Schütt, Jutta ; Oberoi, Raghav ; Schaper, Wolfgang ; Schmitz-Rixen, Thomas ; Schieffer, Bernhard ; Grote, Karsten
Beyond their role in pathogen recognition and the initiation of immune defense, Toll-like receptors (TLRs) are known to be involved in various vascular processes in health and disease. We investigated the potential of the lipopeptide and TLR2/6 ligand macrophage activating protein of 2-kDA (MALP-2) to promote blood flow recovery in mice. Hypercholesterolemic apolipoprotein E (Apoe)-deficient mice were subjected to microsurgical ligation of the femoral artery. MALP-2 significantly improved blood flow recovery at early time points (three and seven days), as assessed by repeated laser speckle imaging, and increased the growth of pre-existing collateral arteries in the upper hind limb, along with intimal endothelial cell proliferation in the collateral wall and pericollateral macrophage accumulation. In addition, MALP-2 increased capillary density in the lower hind limb. MALP-2 enhanced endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) release from endothelial cells and improved the experimental vasorelaxation of mesenteric arteries ex vivo. In vitro, MALP-2 led to the up-regulated expression of major endothelial adhesion molecules as well as their leukocyte integrin receptors and consequently enhanced the endothelial adhesion of leukocytes. Using the experimental approach of femoral artery ligation (FAL), we achieved promising results with MALP-2 to promote peripheral blood flow recovery by collateral artery growth.
Benz, Peter M. ; Merkel, Carla J. ; Offner, Kristin ; Abeßer, Marco ; Ullrich, Melanie ; Fischer, Tobias ; Bayer, Barbara ; Wagner, Helga ; Gambaryan, Stepan ; Ursitti, Jeanine A. ; Adham, Ibrahim M. ; Linke, Wolfgang A. ; Feller, Stephan M. ; Fleming, Ingrid ; Renné, Thomas ; Frantz, Stefan ; Unger, Andreas ; Schuh, Kai
BACKGROUND: In the heart, cytoplasmic actin networks are thought to have important roles in mechanical support, myofibrillogenesis, and ion channel function. However, subcellular localization of cytoplasmic actin isoforms and proteins involved in the modulation of the cytoplasmic actin networks are elusive. Mena and VASP are important regulators of actin dynamics. Due to the lethal phenotype of mice with combined deficiency in Mena and VASP, however, distinct cardiac roles of the proteins remain speculative. In the present study, we analyzed the physiological functions of Mena and VASP in the heart and also investigated the role of the proteins in the organization of cytoplasmic actin networks.
RESULTS: We generated a mouse model, which simultaneously lacks Mena and VASP in the heart. Mena/VASP double-deficiency induced dilated cardiomyopathy and conduction abnormalities. In wild-type mice, Mena and VASP specifically interacted with a distinct αII-Spectrin splice variant (SH3i), which is in cardiomyocytes exclusively localized at Z- and intercalated discs. At Z- and intercalated discs, Mena and β-actin localized to the edges of the sarcomeres, where the thin filaments are anchored. In Mena/VASP double-deficient mice, β-actin networks were disrupted and the integrity of Z- and intercalated discs was markedly impaired.
CONCLUSIONS: Together, our data suggest that Mena, VASP, and αII-Spectrin assemble cardiac multi-protein complexes, which regulate cytoplasmic actin networks. Conversely, Mena/VASP deficiency results in disrupted β-actin assembly, Z- and intercalated disc malformation, and induces dilated cardiomyopathy and conduction abnormalities.
Röllig, Christoph ; Kramer, Michael ; Gabrecht, Maria ; Hänel, Mathias ; Herbst, Regina ; Kaiser, Ulrich ; Schmitz, Norbert ; Kullmer, Johannes ; Fetscher, Sebastian ; Link, Hartmut ; Mantovani Löffler, Luisa ; Krümpelmann, Ulrich ; Neuhaus, Thomas ; Heits, Frank ; Einsele, Hermann ; Ritter, Barbara ; Bornhäuser, Martin ; Schetelig, Johannes ; Thiede, Carsten ; Mohr, Brigitte ; Schaich, Markus ; Platzbecker, Uwe ; Schäfer-Eckart, Kerstin ; Krämer, Alwin ; Berdel, Wolfgang E. ; Serve, Hubert ; Ehninger, Gerhard ; Schuler, Ulrich
Background: The combination of intermediate-dose cytarabine plus mitoxantrone (IMA) can induce high complete remission rates with acceptable toxicity in elderly patients with acute myeloid leukemia (AML). We present the final results of a randomized-controlled trial comparing IMA with the standard 7 + 3 induction regimen consisting of continuous infusion cytarabine plus daunorubicin (DA).
Patients and methods: Patients with newly diagnosed AML >60 years were randomized to receive either intermediate-dose cytarabine (1000 mg/m2 twice daily on days 1, 3, 5, 7) plus mitoxantrone (10 mg/m2 days 1–3) (IMA) or standard induction therapy with cytarabine (100 mg/m2 continuously days 1–7) plus daunorubicin (45 mg/m2 days 3–5) (DA). Patients in complete remission after DA received intermediate-dose cytarabine plus amsacrine as consolidation treatment, whereas patients after IMA were consolidated with standard-dose cytarabine plus mitoxantrone.
Results: Between February 2005 and October 2009, 485 patients were randomized; 241 for treatment arm DA and 244 for IMA; 76% of patients were >65 years. The complete response rate after DA was 39% [95% confidence interval (95% CI): 33–45] versus 55% (95% CI: 49–61) after IMA (odds ratio 1.89, P = 0.001). The 6-week early-death rate was 14% in both arms. Relapse-free survival curves were superimposable in the first year, but separated afterwards, resulting in 3-year relapse-free survival rates of 29% versus 14% in the DA versus IMA arms, respectively (P = 0.042). The median overall survival was 10 months in both arms (P = 0.513).
Conclusion: The dose escalation of cytarabine in induction therapy lead to improved remission rates in the elderly AML patients. This did not translate into a survival advantage, most likely due to differences in consolidation treatment. Thus, effective consolidation strategies need to be further explored. In combination with an effective consolidation strategy, the use of intermediate-dose cytarabine in induction may improve curative treatment for elderly AML patients.
Stratmann, Jan Alexander ; Lacko, Raphael ; Ballo, Olivier ; Shaid, Shabnam ; Gleiber, Wolfgang ; Vehreschild, Maria J. G. T. ; Wichelhaus, Thomas Alexander ; Reinheimer, Claudia ; Göttig, Stephan ; Kempf, Volkhard A. J. ; Kleine, Peter ; Stera, Susanne ; Brandts, Christian Hubertus ; Sebastian, Martin ; Koschade, Sebastian E.
Objectives: Multidrug-resistant organisms (MDRO) are considered an emerging threat worldwide. Data covering the clinical impact of MDRO colonization in patients with solid malignancies, however, is widely missing. We sought to determine the impact of MDRO colonization in patients who have been diagnosed with Non-small cell lung cancer (NSCLC) who are at known high-risk for invasive infections.
Materials and methods: Patients who were screened for MDRO colonization within a 90-day period after NSCLC diagnosis of all stages were included in this single-center retrospective study.
Results: Two hundred and ninety-five patients were included of whom 24 patients (8.1%) were screened positive for MDRO colonization (MDROpos) at first diagnosis. Enterobacterales were by far the most frequent MDRO detected with a proportion of 79.2% (19/24). MDRO colonization was present across all disease stages and more present in patients with concomitant diabetes mellitus. Median overall survival was significantly inferior in the MDROpos study group with a median OS of 7.8 months (95% CI, 0.0–19.9 months) compared to a median OS of 23.9 months (95% CI, 17.6–30.1 months) in the MDROneg group in univariate (p = 0.036) and multivariate analysis (P = 0.02). Exploratory analyses suggest a higher rate of non-cancer-related-mortality in MDROpos patients compared to MDROneg patients (p = 0.002) with an increased rate of fatal infections in MDROpos patients (p = 0.0002).
Conclusions: MDRO colonization is an independent risk factor for inferior OS in patients diagnosed with NSCLC due to a higher rate of fatal infections. Empirical antibiotic treatment approaches should cover formerly detected MDR commensals in cases of (suspected) invasive infections.
Krug, Utz ; Koschmieder, Anja ; Schwammbach, Daniela ; Gerss, Joachim ; Tidow, Nicola ; Steffen, Björn ; Bug, Gesine ; Brandts, Christian Hubertus ; Schaich, Markus ; Röllig, Christoph ; Thiede, Christian ; Noppeney, Richard ; Stelljes, Matthias ; Büchner, Thomas ; Koschmieder, Steffen ; Dührsen, Ulrich ; Serve, Hubert ; Ehninger, Gerhard ; Berdel, Wolfgang E. ; Müller-Tidow, Carsten
INTRODUCTION: Older patients with acute myeloid leukemia (AML) experience short survival despite intensive chemotherapy. Azacitidine has promising activity in patients with low proliferating AML. The aim of this dose-finding part of this trial was to evaluate feasibility and safety of azacitidine combined with a cytarabine- and daunorubicin-based chemotherapy in older patients with AML.
TRIAL DESIGN: Prospective, randomised, open, phase II trial with parallel group design and fixed sample size.
PATIENTS AND METHODS: Patients aged 61 years or older, with untreated acute myeloid leukemia with a leukocyte count of <20,000/µl at the time of study entry and adequate organ function were eligible. Patients were randomised to receive azacitidine either 37.5 (dose level 1) or 75 mg/sqm (dose level 2) for five days before each cycle of induction (7+3 cytarabine plus daunorubicine) and consolidation (intermediate-dose cytarabine) therapy. Dose-limiting toxicity was the primary endpoint.
RESULTS: Six patients each were randomised into each dose level and evaluable for analysis. No dose-limiting toxicity occurred in either dose level. Nine serious adverse events occurred in five patients (three in the 37.5 mg, two in the 75 mg arm) with two fatal outcomes. Two patients at the 37.5 mg/sqm dose level and four patients at the 75 mg/sqm level achieved a complete remission after induction therapy. Median overall survival was 266 days and median event-free survival 215 days after a median follow up of 616 days.
CONCLUSIONS: The combination of azacitidine 75 mg/sqm with standard induction therapy is feasible in older patients with AML and was selected as an investigational arm in the randomised controlled part of this phase-II study, which is currently halted due to an increased cardiac toxicity observed in the experimental arm.
Rieke, Johanna Magdalena ; Zhang, Rong ; Braun, Doreen ; Yilmaz, Öznur ; Japp, Anna S. ; Lopes, Filipa M. ; Pleschka, Michael ; Hilger, Alina Christine ; Schneider, Sophia ; Newman, William G. ; Schneider, Sophia ; Newman, William G. ; Beaman, Glenda M. ; Nordenskjöld, Agneta ; Ebert, Anne-Karoline ; Promm, Martin ; Rösch, Wolfgang H. ; Stein, Raimund ; Hirsch, Karin ; Schäfer, Frank-Mattias ; Schmiedeke, Eberhard ; Boemers, Thomas M. ; Lacher, Martin ; Kluth, Dietrich ; Gosemann, Jan-Hendrik ; Anderberg, Magnus ; Barker, Gillian ; Holmdahl, Gundela ; Läckgren, Göran ; Keene, David ; Cervellione, Raimondo M. ; Giorgio, Elisa ; Di Grazia, Massimo ; Feitz, Wouter F. J. ; Marcelis, Carlo L. M. ; Rooij, Iris Antonia Leonarda Martina van ; Bökenkamp, Arend ; Beckers, Goedele M. A. ; Keegan, Catherine E. ; Sharma, Amit ; Dakal, Tikam Chand ; Wittler, Lars ; Grote, Phillip ; Zwink, Nadine ; Jenetzky, Ekkehart ; Brusco, Alfredo ; Thiele, Holger ; Ludwig, Michael ; Schweizer, Ulrich ; Woolf, Adrian S. ; Odermatt, Benjamin ; Reutter, Heiko
Previous studies in developing Xenopus and zebrafish reported that the phosphate transporter slc20a1a is expressed in pronephric kidneys. The recent identification of SLC20A1 as a monoallelic candidate gene for cloacal exstrophy further suggests its involvement in the urinary tract and urorectal development. However, little is known of the functional role of SLC20A1 in urinary tract development. Here, we investigated this using morpholino oligonucleotide knockdown of the zebrafish ortholog slc20a1a. This caused kidney cysts and malformations of the cloaca. Moreover, in morphants we demonstrated dysfunctional voiding and hindgut opening defects mimicking imperforate anus in human cloacal exstrophy. Furthermore, we performed immunohistochemistry of an unaffected 6-week-old human embryo and detected SLC20A1 in the urinary tract and the abdominal midline, structures implicated in the pathogenesis of cloacal exstrophy. Additionally, we resequenced SLC20A1 in 690 individuals with bladder exstrophy-epispadias complex (BEEC) including 84 individuals with cloacal exstrophy. We identified two additional monoallelic de novo variants. One was identified in a case-parent trio with classic bladder exstrophy, and one additional novel de novo variant was detected in an affected mother who transmitted this variant to her affected son. To study the potential cellular impact of SLC20A1 variants, we expressed them in HEK293 cells. Here, phosphate transport was not compromised, suggesting that it is not a disease mechanism. However, there was a tendency for lower levels of cleaved caspase-3, perhaps implicating apoptosis pathways in the disease. Our results suggest SLC20A1 is involved in urinary tract and urorectal development and implicate SLC20A1 as a disease-gene for BEEC.
Schebelle, Laura ; Wolf, Claudia ; Stribl, Carola ; Javaheri, Tahereh ; Schnütgen, Frank ; Ettinger, Andreas ; Ivics, Zoltán ; Hansen, Jens ; Ruiz, Patricia ; Melchner, Harald von ; Wurst, Wolfgang ; Floss, Thomas
Recombinase-mediated cassette exchange (RMCE) exploits the possibility to unidirectionally exchange any genetic material flanked by heterotypic recombinase recognition sites (RRS) with target sites in the genome. Due to a limited number of available pre-fabricated target sites, RMCE in mouse embryonic stem (ES) cells has not been tapped to its full potential to date. Here, we introduce a universal system, which allows the targeted insertion of any given transcriptional unit into 85 742 previously annotated retroviral conditional gene trap insertions, representing 7013 independent genes in mouse ES cells, by RMCE. This system can be used to express any given cDNA under the control of endogenous trapped promoters in vivo, as well as for the generation of transposon ‘launch pads’ for chromosomal region-specific ‘Sleeping Beauty’ insertional mutagenesis. Moreover, transcription of the gene-of-interest is only activated upon Cre-recombinase activity, a feature that adds conditionality to this expression system, which is demonstrated in vivo. The use of the RMCE system presented in this work requires one single-cloning step followed by one overnight gateway clonase reaction and subsequent cassette exchange in ES cells with efficiencies of 40% in average.
Bickler, Dieter ; Bönsel, Dirk ; Ehmke, Wolfgang ; Engel, Uta ; Gregor, Thomas ; Händler, Arthur ; König, Andreas ; Lange, Ute ; Martiné, Eric ; Merz, Johannes ; Nesemann, Hasko Friedrich ; Nierbauer, Kai Uwe ; Ruppel, Daniel ; Sauerwein, Bernd ; Schrauth, Fabian Etienne ; Schubert, Enno ; Seebauer, Lorenz ; Siebert, Helmut ; Sonnberger, Markus ; Thieme, Michael ; Urbanke, Patrick
Hantson, Stijn ; Arneth, Almut ; Harrison, Sandy P. ; Kelley, Douglas I. ; Prentice, I. Colin ; Rabin, Sam S. ; Archibald, Sally ; Mouillot, Florent ; Arnold, Steve R. ; Artaxo, Paulo ; Bachelet, Dominique ; Ciais, Philippe ; Forrest, Matthew ; Friedlingstein, Pierre ; Hickler, Thomas ; Kaplan, Jed O. ; Kloster, Silvia ; Knorr, Wolfgang ; Lasslop, Gitta ; Li, Fang ; Mangeon, Stephane ; Melton, Joe R. ; Meyn, Andrea ; Sitch, Stephen ; Spessa, Allan ; Werf, Guido R. van der ; Voulgarakis, Apostolos ; Yue, Chao
Biomass burning impacts vegetation dynamics, biogeochemical cycling, atmospheric chemistry, and climate, with sometimes deleterious socio-economic impacts. Under future climate projections it is often expected that the risk of wildfires will increase. Our ability to predict the magnitude and geographic pattern of future fire impacts rests on our ability to model fire regimes, using either well-founded empirical relationships or process-based models with good predictive skill. While a large variety of models exist today, it is still unclear which type of model or degree of complexity is required to model fire adequately at regional to global scales. This is the central question underpinning the creation of the Fire Model Intercomparison Project (FireMIP), an international initiative to compare and evaluate existing global fire models against benchmark data sets for present-day and historical conditions. In this paper we review how fires have been represented in fire-enabled dynamic global vegetation models (DGVMs) and give an overview of the current state of the art in fire-regime modelling. We indicate which challenges still remain in global fire modelling and stress the need for a comprehensive model evaluation and outline what lessons may be learned from FireMIP.
Kiefer, Jan ; Tillein, Jochen ; Ilberg, Christoph von ; Pfenningdorff, Thomas ; Stürzebecher, Ekkehard ; Klinke, Rainer ; Gstöttner, Wolfgang
Electric stimulation of the auditory nerve via cochlear implants has made the treatment of sensory deafness possible. Advanced signal processing and stimulation paradigms have led to continuously improved results in speech understanding. Consequently, indication criteria have been extended to patients with profound and severe-to-profound hearing loss and limited speech understanding with conventional acoustic amplification.
Outside this group, a considerable number of patients presents with rather wellpreserved, low frequency hearing of 30-60 dB up to 1 kHz, but severe loss in the mid to high frequency range of more than 60-70 dB. Monosyllabic word scores in these patients do not generally exceed 35%, due to missing consonant information. But, even increasing the audibility of these high frequencies by acoustic amplification still has very limited efficiency for discriminating speech, and therefore, these patients obtain only minor benefit from conventional hearing aids. On the other hand, standard cochlear implantation would carry a high risk of causing complete hearing loss. This situation has led to considering a combination of both modes of stimulation for these patients who are on the borderline between hearing aids and cochlear implant.
In our present model, the surviving low frequency region of the cochlea could still be stimulated acoustically-combined with additional electrical stimulation of the impaired mid and high frequency region of the cochlea.
Several questions still have to be answered with regard to combined electric and acoustic stimulation (EAS). The possible interaction of electric and acoustic stimuli on the different levels off the auditory system is a major issue. Animal experiments clearly demonstrate that tuning properties of auditory neurons, in response to acute acoustic stimulation, are essentially preserved in the presence of electric stimulation even at high levels of electric stimulation, and that chronic electric stimulation of tie intact inner ear does not have a significant effect on the compound action potentials (CAP) thresholds or inner ear function.
In a previous report, we were able to show that this combined F.A.S of the auditory system is possible in humans, and that it has a synergistic effect on speech understanding. Further major issues regard the surgical feasibility and reproducibility of cochlear implantation with the preservation of residual hearing.
Encouraged by our findings, a clinical study was initiated on the application of EAS. So far, seven adults have been included in this study. In addition, one child has been implanted outside the study.
Martinelli, Paola ; Schaaf, Otmar ; Mantoulidis, Andreas ; Martin, Laetitia J. ; Fuchs, Julian E. ; Bader, Gerd ; Gollner, Andreas ; Wolkerstorfer, Bernhard ; Rogers, Catherine ; Balıkçı, Esra ; Lipp, Jesse J. ; Mischerikow, Nikolai ; Doebel, Sandra ; Gerstberger, Thomas ; Sommergruber, Wolfgang ; Huber, Kilian ; Böttcher, Jark
The bromodomain and PHD-finger containing transcription factor (BPTF) is part of the nucleosome remodeling factor (NURF) complex and has been implicated in multiple cancer types. Here, we report the discovery of a potent and selective chemical probe targeting the bromodomain of BPTF with an attractive pharmacokinetic profile enabling cellular and in vivo experiments in mice. Microarray-based transcriptomics in presence of the probe in two lung cancer cell lines revealed only minor effects on the transcriptome. Profiling against a panel of cancer cell lines revealed that the antiproliferative effect does not correlate with BPTF dependency score in depletion screens. Both observations and the multi-domain architecture of BPTF suggest that depleting the protein by proteolysis targeting chimeras (PROTACs) could be a promising strategy to target cancer cell proliferation. We envision that the presented chemical probe and the related negative control will enable the research community to further explore scientific hypotheses with respect to BPTF bromodomain inhibition.
DGK and DZHK position paper on genome editing: basic science applications and future perspective
(2021)
Brandes, Ralf ; Dueck, Anne ; Engelhardt, Stefan ; Kaulich, Manuel ; Kupatt, Christian ; De Angelis, Maria Teresa ; Leisegang, Matthias ; Le Noble, Ferdinand ; Moretti, Alessandra ; Müller, Oliver J. ; Skryabin, Boris V. ; Thum, Thomas ; Wurst, Wolfgang
For a long time, gene editing had been a scientific concept, which was limited to a few applications. With recent developments, following the discovery of TALEN zinc-finger endonucleases and in particular the CRISPR/Cas system, gene editing has become a technique applicable in most laboratories. The current gain- and loss-of function models in basic science are revolutionary as they allow unbiased screens of unprecedented depth and complexity and rapid development of transgenic animals. Modifications of CRISPR/Cas have been developed to precisely interrogate epigenetic regulation or to visualize DNA complexes. Moreover, gene editing as a clinical treatment option is rapidly developing with first trials on the way. This article reviews the most recent progress in the field, covering expert opinions gathered during joint conferences on genome editing of the German Cardiac Society (DGK) and the German Center for Cardiovascular Research (DZHK). Particularly focusing on the translational aspect and the combination of cellular and animal applications, the authors aim to provide direction for the development of the field and the most frequent applications with their problems.
Kurz, Eduard ; Keller, Matthias ; Schoch, Wolfgang ; Stein, Thomas ; Hirschmüller, Anja ; Niederer, Daniel
Objective: To investigate the feasibility, reliability, and validity of the Modified forward hop (MFH) test in participants after ACL reconstruction (ACLR).
Design: Reliability study.
Setting: Assessments were administered at different clinical locations in Germany and Switzerland by the same 2 investigators.
Participants: Forty-eight active individuals participated in this study (N=48).
Main Outcome Measures: The participants performed MFHs and Forward hops for distance in a predetermined order. The feasibility of the MFH was quantified with proportions of successfully executed attempts and Pearson's χ2 test. Its reliability was estimated using intraclass correlation coefficient (ICC) and standard error of measurement (SEM). Test validity was explored using Pearson's product moment correlation analyses.
Results: Fewer failed attempts were recorded among the participants (age: 30 [Standard deviation 11] years; 22 women, 26 (13) months post-surgery) when compared with the Forward hop for distance test (25/288 trials; 9% vs 72/288 trials; 25%). Within-session ICC values were excellent (>0.95) for both types of Forward hop tests, independent of the side examined. The SEM values were comparable between the Modified (injured: 5.6 cm, uninjured: 5.9 cm) and the classic Forward hop (injured: 4.3 cm, uninjured: 7.2 cm).
Conclusion: The MFH is a feasible, reliable, and valid tool for judging neuromuscular performance after ACLR. If the aim of a hop for distance incorporates enhanced perceived or real landing safety, landing on both feet should be used.
Hinze, Claas Heinrich ; Oommen, Prasad Thomas ; Dressler, Frank ; Urban, Andreas ; Weller-Heinemann, Frank ; Speth, Fabian ; Lainka, Elke ; Brunner, Jürgen ; Fesq, Heike ; Föll, Dirk ; Müller-Felber, Wolfgang ; Neudorf, Ulrich ; Rietschel, Christoph ; Schwarz, Tobias ; Schara, Ulrike ; Haas, Johannes-Peter
Background: Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy in childhood and a major cause of morbidity among children with pediatric rheumatic diseases. The management of JDM is very heterogeneous. The JDM working group of the Society for Pediatric Rheumatology (GKJR) aims to define consensus- and practice-based strategies in order to harmonize diagnosis, treatment and monitoring of JDM.
Methods: The JDM working group was established in 2015 consisting of 23 pediatric rheumatologists, pediatric neurologists and dermatologists with expertise in the management of JDM. Current practice patterns of management in JDM had previously been identified via an online survey among pediatric rheumatologists and neurologists. Using a consensus process consisting of online surveys and a face-to-face consensus conference statements were defined regarding the diagnosis, treatment and monitoring of JDM. During the conference consensus was achieved via nominal group technique. Voting took place using an electronic audience response system, and at least 80% consensus was required for individual statements.
Results: Overall 10 individual statements were developed, finally reaching a consensus of 92 to 100% regarding (1) establishing a diagnosis, (2) case definitions for the application of the strategies (moderate and severe JDM), (3) initial diagnostic testing, (4) monitoring and documentation, (5) treatment targets within the context of a treat-to-target strategy, (6) supportive therapies, (7) explicit definition of a treat-to-target strategy, (8) various glucocorticoid regimens, including intermittent intravenous methylprednisolone pulse and high-dose oral glucocorticoid therapies with tapering, (9) initial glucocorticoid-sparing therapy and (10) management of refractory disease.
Conclusion: Using a consensus process among JDM experts, statements regarding the management of JDM were defined. These statements and the strategies aid in the management of patients with moderate and severe JDM.
Rabl, Regina ; Soubannier, Vincent ; Scholz, Roland ; Vogel, Frank ; Mendl, Nadine ; Vasiljev-Neumeyer, Andreja ; Körner, Christian ; Jagasia, Ravi ; Keil, Thomas ; Baumeister, Wolfgang ; Cyrklaff, Marek ; Neupert, Walter ; Reichert, Andreas
Crista junctions (CJs) are important for mitochondrial organization and function, but the molecular basis of their formation and architecture is obscure. We have identified and characterized a mitochondrial membrane protein in yeast, Fcj1 (formation of CJ protein 1), which is specifically enriched in CJs. Cells lacking Fcj1 lack CJs, exhibit concentric stacks of inner membrane in the mitochondrial matrix, and show increased levels of F1FO–ATP synthase (F1FO) supercomplexes. Overexpression of Fcj1 leads to increased CJ formation, branching of cristae, enlargement of CJ diameter, and reduced levels of F1FO supercomplexes. Impairment of F1FO oligomer formation by deletion of its subunits e/g (Su e/g) causes CJ diameter enlargement and reduction of cristae tip numbers and promotes cristae branching. Fcj1 and Su e/g genetically interact. We propose a model in which the antagonism between Fcj1 and Su e/g locally modulates the F1FO oligomeric state, thereby controlling membrane curvature of cristae to generate CJs and cristae tips.
Wastl, Jürgen ; Duin, Evert C. ; Iuzzolino, Lucia ; Dörner, Wolfgang ; Link, Thomas ; Hoffmann, Silke ; Sticht, Heinrich ; Dau, Holger ; Lingelbach, Klaus ; Maier, Uwe-G.
We analyzed a eukaryotically encoded rubredoxin from the cryptomonad Guillardia theta and identified additional domains at the N- and C-termini in comparison to known prokaryotic paralogous molecules. The cryptophytic N-terminal extension was shown to be a transit peptide for intracellular targeting of the protein to the plastid, whereas a C-terminal domain represents a membrane anchor. Rubredoxin was identified in all tested phototrophic eukaryotes. Presumably facilitated by its C-terminal extension, nucleomorph-encoded rubredoxin (nmRub) is associated with the thylakoid membrane. Association with photosystem II (PSII) was demonstrated by co-localization of nmRub and PSII membrane particles and PSII core complexes and confirmed by comparative electron paramagnetic resonance measurements. The midpoint potential of nmRub was determined as +125 mV, which is the highest redox potential of all known rubredoxins. Therefore, nmRub provides a striking example of the ability of the protein environment to tune the redox potentials of metal sites, allowing for evolutionary adaption in specific electron transport systems, as for example that coupled to the PSII pathway.
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.
Peters-Klimm, Frank ; Müller-Tasch, Thomas ; Schellberg, Dieter ; Gensichen, Jochen ; Muth, Christiane ; Herzog, Wolfgang ; Szecsenyi, Joachim
Background: Chronic congestive heart failure (CHF) is a complex disease with rising prevalence, compromised quality of life (QoL), unplanned hospital admissions, high mortality and therefore high burden of illness. The delivery of care for these patients has been criticized and new strategies addressing crucial domains of care have been shown to be effective on patients' health outcomes, although these trials were conducted in secondary care or in highly organised Health Maintenance Organisations. It remains unclear whether a comprehensive primary care-based case management for the treating general practitioner (GP) can improve patients' QoL. Methods/Design: HICMan is a randomised controlled trial with patients as the unit of randomisation. Aim is to evaluate a structured, standardized and comprehensive complex intervention for patients with CHF in a 12-months follow-up trial. Patients from intervention group receive specific patient leaflets and documentation booklets as well as regular monitoring and screening by a prior trained practice nurse, who gives feedback to the GP upon urgency. Monitoring and screening address aspects of disease-specific selfmanagement, (non)pharmacological adherence and psychosomatic and geriatric comorbidity. GPs are invited to provide a tailored structured counselling 4 times during the trial and receive an additional feedback on pharmacotherapy relevant to prognosis (data of baseline documentation). Patients from control group receive usual care by their GPs, who were introduced to guidelineoriented management and a tailored health counselling concept. Main outcome measurement for patients' QoL is the scale physical functioning of the SF-36 health questionnaire in a 12-month follow-up. Secondary outcomes are the disease specific QoL measured by the Kansas City Cardiomyopathy questionnaire (KCCQ), depression and anxiety disorders (PHQ-9, GAD-7), adherence (EHFScBS and SANA), quality of care measured by an adapted version of the Patient Chronic Illness Assessment of Care questionnaire (PACIC) and NTproBNP. In addition, comprehensive clinical data are collected about health status, comorbidity, medication and health care utilisation. Discussion: As the targeted patient group is mostly cared for and treated by GPs, a comprehensive primary care-based guideline implementation including somatic, psychosomatic and organisational aspects of the delivery of care (HICMAn) is a promising intervention applying proven strategies for optimal care. Trial registration: Current Controlled Trials ISRCTN30822978.