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12. Multiomic factor analysis for pathologic complete response (pCR) after 12 weeks of pembrolizumab + trastuzumab + pertuzumab in HER2-enriched (HER2-E) early breast cancer (eBC) in the Keyriched-1 trial.

Author

Graeser, Monika Karla, primary, Gluz, Oleg, additional, Schmid, Peter, additional, Jozwiak, Katarzyna, additional, Feuerhake, Friedrich, additional, Volk, Valery, additional, Ulbrich-Gebauer, Daniel, additional, Biehl, Claudia, additional, Reinisch, Mattea, additional, Luedtke-Heckenkamp, Kerstin, additional, Hartkopf, Andreas D., additional, Hilpert, Felix, additional, Braun, Michael, additional, Blohmer, Jens U., additional, Christgen, Matthias, additional, Kreipe, Hans Heinrich, additional, Nitz, Ulrike, additional, Pelz, Enrico, additional, Harbeck, Nadia, additional, and Kuemmel, Sherko, additional

Published
2024
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18. Table Graphs

Author

Zündorf, Albert, Gebauer, Daniel, Reichmann, Clemens, Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Weikum, Gerhard, Series editor, de Lara, Juan, editor, and Plump, Detlef, editor

Published
2017
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20. Interrelated dataset of rebound numbers, ultrasonic pulse velocities and compressive strengths of drilled concrete cores from an existing structure and new fabricated concrete cubes

Author

Gebauer, Daniel, primary, Gutierrez, Raúl Enríque Beltrán, additional, Marx, Steffen, additional, Butler, Marko, additional, Grahl, Konrad, additional, Thiel, Thomas, additional, Maack, Stefan, additional, Küttenbaum, Stefan, additional, Pirskawetz, Stephan, additional, Breit, Wolfgang, additional, Schickert, Martin, additional, and Krüger, Marco, additional

Published
2023
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21. Prognostic and predictive impact of gene expression in node‐positive early breast cancer patients receiving dose‐dense versus standard‐dose adjuvant chemotherapy

Author

Reinisch, Mattea, primary, Bruzas, Simona, additional, Gluz, Oleg, additional, Ataseven, Beyhan, additional, Schmid, Peter, additional, Cortés, Javier, additional, Blohmer, Jens‐Uwe, additional, Shenoy, Satyendra, additional, Dyson, Mark H., additional, Dittmer‐Grabowski, Christine, additional, Chiari, Ouafaa, additional, Harrach, Hakima, additional, Gebauer, Daniel, additional, Traut, Alexander, additional, and Kuemmel, Sherko, additional

Published
2023
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22. Supplementary Figure from De-escalated Neoadjuvant Chemotherapy in Early Triple-Negative Breast Cancer (TNBC): Impact of Molecular Markers and Final Survival Analysis of the WSG-ADAPT-TN Trial

Author

Gluz, Oleg, primary, Nitz, Ulrike, primary, Kolberg-Liedtke, Cornelia, primary, Prat, Aleix, primary, Christgen, Matthias, primary, Kuemmel, Sherko, primary, Mohammadian, Mohammad Parsa, primary, Gebauer, Daniel, primary, Kates, Ronald, primary, Paré, Laia, primary, Grischke, Eva-Maria, primary, Forstbauer, Helmut, primary, Braun, Michael, primary, Warm, Mathias, primary, Hackmann, John, primary, Uleer, Christoph, primary, Aktas, Bahriye, primary, Schumacher, Claudia, primary, Wuerstlein, Rachel, primary, Graeser, Monika, primary, Pelz, Enrico, primary, Jóźwiak, Katarzyna, primary, zu Eulenburg, Christine, primary, Kreipe, Hans Heinrich, primary, and Harbeck, Nadia, primary

Published
2023
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23. "Supplementary Table S5 from Impact of RNA Signatures on pCR and Survival after 12-Week Neoadjuvant Pertuzumab plus Trastuzumab with or without Paclitaxel in the WSG-ADAPT HER2+/HR− Trial

Author

Graeser, Monika, primary, Gluz, Oleg, primary, Biehl, Claudia, primary, Ulbrich-Gebauer, Daniel, primary, Christgen, Matthias, primary, Palatty, Jenci, primary, Kuemmel, Sherko, primary, Grischke, Eva-Maria, primary, Augustin, Doris, primary, Braun, Michael, primary, Potenberg, Jochem, primary, Wuerstlein, Rachel, primary, Krauss, Katja, primary, Schumacher, Claudia, primary, Forstbauer, Helmut, primary, Reimer, Toralf, primary, Stefek, Andrea, primary, Fischer, Hans Holger, primary, Pelz, Enrico, primary, zu Eulenburg, Christine, primary, Kates, Ronald, primary, Ni, Hua, primary, Kolberg-Liedtke, Cornelia, primary, Feuerhake, Friedrich, primary, Kreipe, Hans Heinrich, primary, Nitz, Ulrike, primary, and Harbeck, Nadia, primary

Published
2023
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24. Crack monitoring on concrete structures: Comparison of various distributed fiber optic sensors with digital image correlation method.

Author

Herbers, Max, Richter, Bertram, Gebauer, Daniel, Classen, Martin, and Marx, Steffen

Subjects
DIGITAL image correlation, CRACKING of concrete, OPTICAL fiber detectors, IMAGE sensors, STRAIN gages, REINFORCED concrete, DIGITAL images
Abstract

The quality of strain measurements using distributed fiber optic sensors (DFOS) depends largely on the bond between the host material and the optical fiber. Experimental investigations were carried out to test the suitability of five different DFOS types for crack monitoring. The DFOS were subsequently bonded to two 4 m long reinforced concrete (RC) beams, so that the influence of the application technique could be evaluated. DFOS measurements were verified by digital image correlation (DIC) and electrical strain gauges (SGs). For the different DFOS types, clear differences in the measured strain curves and determined crack widths were observed. The focus was on two robust DFOS, which can be deployed on construction sites. Compared to the layered sensing cable, a monolithic DFOS showed a clear strain distribution with pronounced strain peaks even for closely spaced cracks. The crack widths obtained by integrating the strain curves showed high agreement with DIC measurements. [ABSTRACT FROM AUTHOR]

Published
2023
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26. Abstract P5-02-03: Combined biomarker analysis for prediction of pathological complete response (pCR) after 12 weeks of pembrolizumab + trastuzumab + pertuzumab in HER2-enriched early breast cancer: Keyriched-1 trial

Author

Graeser, Monika, primary, Kuemmel, Sherko, additional, Gluz, Oleg, additional, Feuerhake, Friedrich, additional, Volk, Valery, additional, Ulbrich-Gebauer, Daniel, additional, Biehl, Claudia, additional, Reinisch, Mattea, additional, Kostara9, Athina, additional, Scheffen, Iris, additional, Luedtke-Heckenkamp, Kerstin, additional, Hartkopf, Andreas, additional, Hilpert, Felix, additional, Kentsch, Angela, additional, Ziske, Carsten, additional, Depenbusch, Reinhard, additional, Braun, Michael, additional, Blohmer, Jens-Uwe, additional, zu Eulenburg, Christine, additional, Christgen, Matthias, additional, Kates, Ronald, additional, Bartels, Stephan, additional, Kreipe, Hans-Heinrich, additional, Pelz, Enrico, additional, Schmid, Peter, additional, and Harbeck, Nadia, additional

Published
2023
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29. Impact of RNA Signatures on pCR and Survival after 12-Week Neoadjuvant Pertuzumab plus Trastuzumab with or without Paclitaxel in the WSG-ADAPT HER2+/HR− Trial

Author

Graeser, Monika, Gluz, Oleg, Biehl, Claudia, Ulbrich-Gebauer, Daniel, Christgen, Matthias, Palatty, Jenci, Kuemmel, Sherko, Grischke, Eva-Maria, Augustin, Doris, Braun, Michael, Potenberg, Jochem, Wuerstlein, Rachel, Krauss, Katja, Schumacher, Claudia, Forstbauer, Helmut, Reimer, Toralf, Stefek, Andrea, Fischer, Hans Holger, Pelz, Enrico, Zu Eulenburg, Christine, Kates, Ronald, Ni, Hua, Kolberg-Liedtke, Cornelia, Feuerhake, Friedrich, Kreipe, Hans Heinrich, Nitz, Ulrike, Harbeck, Nadia, and WSG-ADAPT Investigators

Subjects
Cancer Research, Oncology, Medizin
Abstract

Clinical cancer research 29(4), 805-814 (2023). doi:10.1158/1078-0432.CCR-22-1587, Published by AACR, Philadelphia, Pa. [u.a.]

Published
2023
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30. Impact of RNA Signatures on pCR and Survival after 12-Week Neoadjuvant Pertuzumab plus Trastuzumab with or without Paclitaxel in the WSG-ADAPT HER2+/HR− Trial

Author

Graeser, Monika, primary, Gluz, Oleg, additional, Biehl, Claudia, additional, Ulbrich-Gebauer, Daniel, additional, Christgen, Matthias, additional, Palatty, Jenci, additional, Kuemmel, Sherko, additional, Grischke, Eva-Maria, additional, Augustin, Doris, additional, Braun, Michael, additional, Potenberg, Jochem, additional, Wuerstlein, Rachel, additional, Krauss, Katja, additional, Schumacher, Claudia, additional, Forstbauer, Helmut, additional, Reimer, Toralf, additional, Stefek, Andrea, additional, Fischer, Hans Holger, additional, Pelz, Enrico, additional, zu Eulenburg, Christine, additional, Kates, Ronald, additional, Ni, Hua, additional, Kolberg-Liedtke, Cornelia, additional, Feuerhake, Friedrich, additional, Kreipe, Hans Heinrich, additional, Nitz, Ulrike, additional, and Harbeck, Nadia, additional

Published
2022
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32. Table Graphs

Author

Zündorf, Albert, primary, Gebauer, Daniel, additional, and Reichmann, Clemens, additional

Published
2017
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33. Molecular Subtyping of Invasive Breast Cancer Using a PAM50-Based Multigene Expression Test-Comparison with Molecular-Like Subtyping by Tumor Grade/Immunohistochemistry and Influence on Oncologist’s Decision on Systemic Therapy in a Real-World Setting

Author

Erber, Ramona, primary, Angeloni, Miriam, additional, Stöhr, Robert, additional, Lux, Michael P., additional, Ulbrich-Gebauer, Daniel, additional, Pelz, Enrico, additional, Bankfalvi, Agnes, additional, Schmid, Kurt W., additional, Walter, Robert F. H., additional, Vetter, Martina, additional, Thomssen, Christoph, additional, Mayr, Doris, additional, Klauschen, Frederick, additional, Sinn, Peter, additional, Sotlar, Karl, additional, Stering, Katharina, additional, Stenzinger, Albrecht, additional, Wunderle, Marius, additional, Fasching, Peter A., additional, Beckmann, Matthias W., additional, Hoffmann, Oliver, additional, Kimmig, Rainer, additional, Harbeck, Nadia, additional, Wuerstlein, Rachel, additional, Ferrazzi, Fulvia, additional, and Hartmann, Arndt, additional

Published
2022
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34. Distributed fiber optic sensors for measuring strains of concrete, steel, and textile reinforcement

Author

Zdanowicz, Katarzyna, Gebauer, Daniel, Speck, Kerstin, Steinbock, Oliver, Beckmann, Birgit, Marx, Steffen, Koschemann, Marc, Zdanowicz, Katarzyna, Gebauer, Daniel, Speck, Kerstin, Steinbock, Oliver, Beckmann, Birgit, Marx, Steffen, and Koschemann, Marc

Abstract

The article describes measurements of strains of concrete, steel and textile reinforcement with distributed fiber optic sensors (DFOS). The technology of distributed strain measurements gains currently increasing attention within the civil engineering field and indeed the DFOS can be applied in various measurement scenarios providing results and insights which were not possible before. Within this article, the fibers and adhesives that are most commonly used are compared and several measurement scenarios and their results are described, including precise strain measurements with high resolution as well as measurements on large-scale specimens. Concrete strains were measured in a multiaxial compression stress state and also during setting and hardening and in flexural tests. Strains of the steel and textile reinforcement were monitored along the bond zone and also in flexural tests. Finally, cracking patterns were observed and compared with digital image correlation methods. Validated examples of applications of DFOS in laboratory work are described.

Published
2022

35. Rissbildung und Rissbreitenentwicklung bei Stahlbetonbauteilen unter verformungsinduziertem Zwang

Author

Deutscher Ausschuss für Stahlbeton e.V. (DAfStb), Gebauer, Daniel, Deutscher Ausschuss für Stahlbeton e.V. (DAfStb), and Gebauer, Daniel

Abstract

Der vorliegende Beitrag befasst sich – motiviert vom Detail des monolithischen Anschlusspunktes der Stützen an den Überbau semi-integraler Brücken und den damit einhergehenden Besonderheiten für den Entwurf – mit der Thematik der verformungsinduzierten Rissbildung und ihren Einflussfaktoren. Anhand zweier Versuchsreihen wird der Einfluss der geometrischen Querschnittsparameter (Bewehrungsgrad, Bewehrungsumfang und Anzahl der Bewehrungslagen) auf die Rissbildung infolge Zwangsverformung untersucht.

Published
2022

36. De-escalated Neoadjuvant Chemotherapy in Early Triple-Negative Breast Cancer (TNBC): Impact of Molecular Markers and Final Survival Analysis of the WSG-ADAPT-TN Trial

Author

Gluz, Oleg, Nitz, Ulrike, Kolberg-Liedtke, Cornelia, Prat, Aleix, Christgen, Matthias, Kuemmel, Sherko, Mohammadian, Mohammad Parsa, Gebauer, Daniel, Kates, Ronald, Pare, Laia, Grischke, Eva-Maria, Forstbauer, Helmut, Braun, Michael, Warm, Mathias, Hackmann, John, Uleer, Christoph, Aktas, Bahriye, Schumacher, Claudia, Wuerstlein, Rachel, Graeser, Monika, Pelz, Enrico, Jozwiak, Katarzyna, Zu Eulenburg, Christine, Kreipe, Hans Heinrich, Harbeck, Nadia, Gluz, Oleg, Nitz, Ulrike, Kolberg-Liedtke, Cornelia, Prat, Aleix, Christgen, Matthias, Kuemmel, Sherko, Mohammadian, Mohammad Parsa, Gebauer, Daniel, Kates, Ronald, Pare, Laia, Grischke, Eva-Maria, Forstbauer, Helmut, Braun, Michael, Warm, Mathias, Hackmann, John, Uleer, Christoph, Aktas, Bahriye, Schumacher, Claudia, Wuerstlein, Rachel, Graeser, Monika, Pelz, Enrico, Jozwiak, Katarzyna, Zu Eulenburg, Christine, Kreipe, Hans Heinrich, and Harbeck, Nadia

Abstract

Purpose: Although optimal treatment in early triple-negative breast cancer (TNBC) remains unclear, de-escalated chemother-apy appears to be an option in selected patients within this aggressive subtype. Previous studies have identified several pro -immune factors as prognostic markers in TNBC, but their predictive impact regarding different chemotherapy strategies is still controversial.Experimental Design: ADAPT-TN is a randomized neoadju-vant multicenter phase II trial in early patients with TNBC (n = 336) who were randomized to 12 weeks of nab-paclitaxel 125 mg/m2 thorn gemcitabine or carboplatin d 1,8 q3w. Omission of further (neo-) adjuvant chemotherapy was allowed only in patients with patho-logical complete response [pCR, primary endpoint (ypT0/is, ypN0)]. Secondary invasive/distant disease-free and overall survival (i/dDFS, OS) and translational research objectives included quantification of a predictive impact of markers regard-ing selection for chemotherapy de-escalation, measured by gene expression of 119 genes (including PAM50 subtype) by nCounter platform and stromal tumor-infiltrating lymphocytes (sTIL).Results: After 60 months of median follow-up, 12-week-pCR was favorably associated (HR, 0.24; P = 0.001) with 5y-iDFS of 90.6% versus 62.8%. No survival advantage of carboplatin use was observed, despite a higher pCR rate [HR, 1.04; 95% confidence interval (CI), 0.68-1.59]. Additional anthracycline-containing che-motherapy was not associated with a significant iDFS advantage in pCR patients (HR, 1.29; 95% CI, 0.41-4.02). Beyond pCR rate, nodal status and high sTILs were independently associated with better iDFS, dDFS, and OS by multivariable analysis.Conclusions: Short de-escalated neoadjuvant taxane/platinum-based combination therapy appears to be a promising strategy in early TNBC for using pCR rate as an early decision point for further therapy (de-) escalation together with node-negative status and high sTILs.

Published
2022

39. Efficacy of deescalated chemotherapy according to PAM50 subtypes, immune and proliferation genes in triple-negative early breast cancer: Primary translational analysis of the WSG-ADAPT-TN trial

Author

Gluz, Oleg, Kolberg-Liedtke, Cornelia, Prat, Aleix, Christgen, Matthias, Gebauer, Daniel, Kates, Ronald, Pare, Laia, Grischke, Eva-Maria, Forstbauer, Helmut, Braun, Michael, Warm, Mathias, Hackmann, John, Uleer, Christoph, Aktas, Bahriye, Schumacher, Claudia, Kuemmel, Sherko, Wuerstlein, Rachel, Pelz, Enrico, Nitz, Ulrike, Kreipe, Hans Heinrich, Harbeck, Nadia, Gluz, Oleg, Kolberg-Liedtke, Cornelia, Prat, Aleix, Christgen, Matthias, Gebauer, Daniel, Kates, Ronald, Pare, Laia, Grischke, Eva-Maria, Forstbauer, Helmut, Braun, Michael, Warm, Mathias, Hackmann, John, Uleer, Christoph, Aktas, Bahriye, Schumacher, Claudia, Kuemmel, Sherko, Wuerstlein, Rachel, Pelz, Enrico, Nitz, Ulrike, Kreipe, Hans Heinrich, and Harbeck, Nadia

Abstract

In the neoadjuvant WSG-ADAPT-TN trial, 12-week nab-paclitaxel + carboplatin (nab-pac/carbo) was highly effective and superior to nab-paclitaxel + gemcitabine (nab-pac/gem) in triple-negative breast cancer regarding pathological complete response (pCR). Predictive markers for deescalated taxane/carbo use in TNBC need to be identified. Patients received 4 x nab-pac 125 mg/m(2) (plus carbo AUC2 or gem 1,000 mg/m(2) d1,8 q21). Expression of 119 genes and PAM50 scores by nCounter were available in 306/336 pretherapeutic samples. Interim survival analysis was planned after 36 months median follow-up. Basal-like (83.3%) compared to other subtypes was positively associated with pCR (38% vs. 20%, p = 0.015), as was lower HER2 score (p < 0.001). Proliferation biomarkers were positively associated with pCR, that is, PAM50 proliferation, ROR scores (all p < 0.004), higher Ki-67 (IHC; p < 0.001). For nab-pac/carbo, expression of immunological (CD8, PD1 and PFDL1) genes and proliferation markers (proliferation and ROR scores, MKI67, CDC20, NUF2, KIF2C, CENPF, EMP3 and TYMS) were positively associated with pCR (p < 0.05 for all). For nab-pac/gem, angiogenesis genes were negatively associated with pCR (ANGPTL4: p = 0.05; FGFR4: p = 0.02; VEGFA: p = 0.03). pCR after 12 weeks was strongly associated with favorable outcome (3y event-free survival: 92% vs. 71%, p < 0.001). In early TNBC, basal-like subtype, higher Ki-67 (IHC) and lower HER2 score were, associated with chemosensitivity. Chemoresistance pathways differed between the two taxane based combinations. Combination of proliferation/immune markers and PAM50 subtype could allow patient selection for further deescalated chemotherapy and/or immune treatment approaches.

Published
2020

41. Abstract PD5-09: Prognostic and predictive impact of genes and signatures measured with the BC360 panel (Nanostring) in node positive (≥pN2a) high risk patients (pts) receiving dose dense (dd) versus standard dosed chemotherapy in an adjuvant randomized trial with a long term follow-up (FU)

Author

Reinisch, Mattea, primary, Gluz, Oleg, additional, Ataseven, Beyhan, additional, Schmid, Peter, additional, Blohmer, Jens-Uwe, additional, Dittmer-Grabwoski, Christine, additional, Rueland, Anna, additional, Bruzas, Simona, additional, Seiberling, Christine, additional, Harrach, Hakima, additional, Gebauer, Daniel, additional, Traut, Alexander, additional, and Kuemmel, Sherko, additional

Published
2020
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42. Genomic markers but not molecular subtypes provide prognostic impact and predict anthracycline efficacy in early triple-negative breast cancer : Results from the prospective WSG PlanB trial

Author

Gluz, Oleg, Liedtke, Cornelia, Prat, Aleix, Christgen, Matthias, Gebauer, Daniel, Kates, Ronald, Pelz, Enrico, Clemens, Michael, Warm, Matthias, Aktas, Bahriye, Kuemmel, Sherko, Pare, Laia, Krabisch, Petra, Kreipe, Hans H., Wuerstlein, Rachel, Nitz, Ulrike, Harbeck, Nadia, and West German Study Grp

Subjects
Medizin, ComputingMethodologies_GENERAL
Abstract

Poster-Abstract

Published
2018

43. Efficacy of deescalated chemotherapy according to PAM50 subtypes, immune and proliferation genes in triple‐negative early breast cancer: Primary translational analysis of the WSG‐ADAPT‐TN trial

Author

Gluz, Oleg, primary, Kolberg‐Liedtke, Cornelia, additional, Prat, Aleix, additional, Christgen, Matthias, additional, Gebauer, Daniel, additional, Kates, Ronald, additional, Paré, Laia, additional, Grischke, Eva‐Maria, additional, Forstbauer, Helmut, additional, Braun, Michael, additional, Warm, Mathias, additional, Hackmann, John, additional, Uleer, Christoph, additional, Aktas, Bahriye, additional, Schumacher, Claudia, additional, Kuemmel, Sherko, additional, Wuerstlein, Rachel, additional, Pelz, Enrico, additional, Nitz, Ulrike, additional, Kreipe, Hans Heinrich, additional, and Harbeck, Nadia, additional

Published
2019
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45. Beurteilung der Festigkeitseigenschaften bestehender Talbrücken aus Spannbeton: Materialuntersuchungen an Betonproben der Lahntalbrücke bei Limburg.

Author

Gebauer, Daniel, Schmidt, Boso, Schacht, Gregor, and Marx, Steffen

Subjects
*PRESTRESSED concrete, *TENSILE strength, *COMPRESSIVE strength, *EXPECTED returns, *VALUATION of real property, *PRESTRESSED concrete beams
Abstract

Assessment of strength properties of viaducts made of prestressed concrete – Material investigations on concrete samples from the Lahntal Viaduct near Limburg In 2016 the Lahntal Viaduct was replaced by a new structure. Before the western superstructure was deconstructed, more than 250 cores and other specimens could be taken from the old structure. The present paper deals with the investigations on compressive strength and tensile splitting strength of the concrete. The test results are evaluated statistically and different populations are tested for the taken sample. The goal is to identify a reasonable subdivision of the sample. Furthermore, the design values according to DIN EN 13791 and Eurocode 0 were calculated and compared with calculated expected values. These investigations are intended to provide insights for the assessment of the strength properties of existing viaducts and to develop a safe and economical investigation methodology from them. [ABSTRACT FROM AUTHOR]

Published
2021
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49. Criteria and influencing parameters for the design of piers of semi‐integral bridges.

Author

Gebauer, Daniel, Stümpel, Marina, Von Der Haar, Christoph, and Marx, Steffen

Subjects
*PIERS -- Design & construction, *NORMAL force (Mechanics), *STIFFNESS (Mechanics), *DUCTILITY, *MOMENTS of inertia
Abstract

This article deals with the challenges of semi‐integral construction of long viaducts. The main characteristic of semi‐integral bridges is the monolithic connection of most parts of the substructure with the superstructure. This leads to complex load‐bearing behavior, in which several structural components interact with each other. Because of the longitudinal movement of the superstructure, constraint forces and moments occur in the piers. They induce additional stresses in the structure compared to conventionally supported bridges. An important issue during the design process is the choice of the pier cross section. The stiffness and ductility of the piers influence the constraint moments and failure behavior of the pier. This is the reason why the detailed investigation into the influencing parameters (normal‐force utilization, reinforcement ratio, and width‐to‐height ratio) described in this paper was carried out. In this investigation, the moment–curvature relationship was used and the failure behavior as well as the constraint moments in the structure were evaluated. [ABSTRACT FROM AUTHOR]

Published
2018
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50. Impact of RNA Signatures on pCR and Survival after 12-Week Neoadjuvant Pertuzumab plus Trastuzumab with or without Paclitaxel in the WSG-ADAPT HER2+/HR- Trial.

Author

Graeser M, Gluz O, Biehl C, Ulbrich-Gebauer D, Christgen M, Palatty J, Kuemmel S, Grischke EM, Augustin D, Braun M, Potenberg J, Wuerstlein R, Krauss K, Schumacher C, Forstbauer H, Reimer T, Stefek A, Fischer HH, Pelz E, Zu Eulenburg C, Kates R, Ni H, Kolberg-Liedtke C, Feuerhake F, Kreipe HH, Nitz U, and Harbeck N

Subjects
Humans, Female, Trastuzumab therapeutic use, Neoadjuvant Therapy, Biomarkers, Tumor metabolism, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Receptor, ErbB-2 metabolism, RNA, Paclitaxel therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms genetics, Breast Neoplasms pathology
Abstract

Purpose: To identify associations of biological signatures and stromal tumor-infiltrating lymphocytes (sTIL) with pathological complete response (pCR; ypT0 ypN0) and survival in the Phase II WSG-ADAPT HER2+/HR- trial (NCT01817452)., Experimental Design: Patients with cT1-cT4c, cN0-3 HER2+/HR- early breast cancer (EBC) were randomized to pertuzumab+trastuzumab (P+T, n = 92) or P+T+paclitaxel (n = 42). Gene expression signatures were analyzed in baseline biopsies using NanoString Breast Cancer 360 panel (n = 117); baseline and on-treatment (week 3) sTIL levels were available in 119 and 76 patients, respectively. Impacts of standardized gene expression signatures on pCR and invasive disease-free survival (iDFS) were estimated by logistic and Cox regression., Results: In all patients, ERBB2 [OR, 1.70; 95% confidence interval (CI), 1.08-2.67] and estrogen receptor (ER) signaling (OR, 1.72; 95% CI, 1.13-2.61) were favorable, whereas PTEN (OR, 0.57; 95% CI, 0.38-0.87) was unfavorable for pCR. After 60 months median follow-up, 13 invasive events occurred (P+T: n = 11, P+T+paclitaxel: n = 2), none following pCR. Gene signatures related to immune response (IR) and ER signaling were favorable for iDFS, all with similar HR about 0.43-0.55. These patterns were even more prominent in the neoadjuvant chemotherapy-free group, where additionally BRCAness signature was unfavorable (HR, 2.00; 95% CI, 1.04-3.84). IR signatures were strongly intercorrelated. sTILs (baseline/week 3/change) were not associated with pCR or iDFS, though baseline sTILs correlated positively with IR signatures., Conclusions: Distinct gene signatures were associated with pCR versus iDFS in HER2+/HR- EBC. The potential role of IR in preventing recurrence suggests that patients with upregulated IR signatures could be candidates for de-escalation concepts in HER2+ EBC., (©2022 The Authors; Published by the American Association for Cancer Research.)

Published
2023
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