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2. Teachers in the UK Prefer Research Evidence that is Synthesized, Practical, and Locally Available. A Review of: Williams, Dorothy and Louisa Coles. 'Evidence-Based Practice in Teaching: An Information Perspective.' Journal of Documentation 63.6 (2007): 812-35.

Author

Stephanie Schulte

Subjects
Bibliography. Library science. Information resources
Abstract

Objective – The objective of the study was to explore how teachers in the United Kingdom use research literature to inform their practice. Special emphasis was given to the effect of the teachers’ information literacy and their level of ready access to research information.Design – This study was primarily a qualitative study utilizing mixed methods, including individual interviews, focus groups (“literature review groups”), and an online discussion forum. Qualitative data was supplemented by a questionnaire survey.Setting – The qualitative portions of the study took place in the United Kingdom across five education authorities; however, it is unclear where these authorities were geographically. The survey was distributed across Scotland, England, and Wales. The study was conducted during 2002 to 2003. Subjects – Nursery, primary, and secondary teachers, school librarians, school library systems, and education authority advisors (EA) in the United Kingdom. Methods – The 28 interviews (54% primary teachers, 39% secondary teachers, 7% special education) and four focus groups (each with three to five participants; 15 participants in total, including teachers at various levels from primary, secondary, and nursery schools) were conducted with volunteers from a random sample across five education authorities. Recruitment was done by sending written materials to schools. Those interviewed represented five authorities. Focus groups were conducted in just four authorities. It is not clear when the individual and group interviews were conducted (time of day and year). Volunteers were given the option to receive funding for a substitute teacher in order to participate, though none took advantage of this offer. The interview process used a vignette technique to elicit teachers’ attitudes to a situation in a non-threatening way. Interviewees were asked to comment on two situations that might make them seek information. One was adding a new subject or new aspect of an existing subject into the classroom. The second dealt with a “new pedagogical challenge.” Though the topics of the vignettes were provided, the exact way the topics were presented was not. They were asked how they would advise another teacher in these situations then relate their thoughts to a real situation they had faced. Interviews were about one hour in length. Twenty-five of the 28 interviews were taped and transcribed verbatim. Extensive notes were made for the other three. Transcripts and notes were analyzed using QSR N4 Classic content analysis software. Themes related to information literacy and information seeking, including barriers, were noted. Four literature response groups were given examples of research information (journal articles, reports, etc) related to information computer technology (ICT) and class size. Each topic had information from various evidence levels and included both print and electronic format. Again, the discussion topics were provided in the article, but the exact way the topics were presented was not. Over 2 to 2.5 hours, teachers read the materials, made notes, and discussed the information as a group. For the ICT information, groups were asked to discuss presentation of the information. For the class size information, groups were asked to discuss content of the materials. Discussions were transcribed verbatim and analyzed with the content analysis software. A total of 3899 questionnaire surveys were distributed to teachers (3000), head teachers (500), school librarians (250), education authority advisors (100), and school library systems (49). Response rate was exceptionally low in the teacher and head teacher categories, with only 10.9% of teachers and 15.6% of head teachers responding. Response rates in other categories ranged from 31.2% to 55%, with the highest response rates from education authorities and school library systems. The survey served to gain an understanding of attitudes about using research in practice across a broad spectrum of stakeholders. The survey instrument itself, which was not provided in the article, was piloted prior to the study, but there is no mention of reliability or validity analysis. To supplement study data, participants who had stated they would be interested in participating in an online discussion were sent preliminary findings and asked to comment on themes using the online discussion forum. Only 21 posts were gathered using this method. Overall, the methods used in this study are appropriate for the questions that were posed in the article. Qualitative studies are useful for gathering data where little is known and where more data would help identify possibly hypotheses for further study.Main Results – Teachers in this study relied on a small set of resources and preferred what was readily available at their ownschool. These teachers most frequently used colleagues, in-service events, the Internet, newspapers, and reports typically found in schools as sources of information. Sources that information professionals would consider quality evidence were rarely mentioned. These teachers also tended to prefer sources that present information in a practical context. Not surprisingly, time was identified as a major barrier to accessing research information in addition to limited access to resources. The Internet was identified as the preferred point of access, citing ease of use, speed, and convenience as the reasons for this preference. Comments suggested a preference for synthesized information sources. Teachers indicated they felt the responsibility for disseminating research information fell on head teachers and EA. They also noted that access to information from their own school library was a problem. They felt librarians and libraries in schools were meant for students, not for teachers, and also expressed that school libraries typically did not provide access to research. Comments suggested that the structure of teaching in a classroom itself does not allow teachers to use information as is needed for evidence-based practice. There were concerns expressed about lack of school library funding available to supply research evidence needed by teachers. School librarians and school library services respondents did indicate that they provide abroad range of services aimed at teachers, such as alerts to literature, information skills training, and advice on resources. However, their sources of research for teachers were limited in nature. Librarians indicated that teachers did not ask for research information, but if demand were there, they could respond accordingly. Teacher comments suggest that librarians might want to consider being more proactive in distributing information. Though teachers expressed high confidence in their abilities to find information, comments about search habits and practices contradicted this. Most remarks suggested searching techniques that were not sophisticated or showing higher levels of information literacy competency. The respondents were concerned with evaluating the quality of information sources but found this appraisal to be more difficult if the authors did not explain the impact or change in practice that should come from the findings. The participants in this study were likely biased toward using research information more than other teachers. This is an important limitation that the authors do address. Additionally, the response rate for the survey was quite low for the teacher subset. Despite this limitation, data from the questionnaire was used appropriately to confirm and clarify data from the qualitative portions of the study.Conclusion – In order for teachers to appreciate the value of quality research evidence enough to regularly seek it out and place it into practice, a culture of evidence based practice must be embraced and supported by their school authorities. This study indicates significant potential for school librarians and systems to support this culture through proactive dissemination of research, provision of local access to materials, and education related to information literacy. School librarians must evolve from their typical student-centric role to accomplish this.

Published
2008

3. Molecular and immunohistochemical characterisation of mesothelioma of the tunica vaginalis

Author

William J Anderson, Lynette M Sholl, Christopher D M Fletcher, Stephanie Schulte, Li Juan Wang, Fiona M Maclean, and Michelle S Hirsch

Subjects
Adenomatoid Tumor, Male, Histology, Tumor Suppressor Proteins, Mesothelioma, Malignant, General Medicine, Immunohistochemistry, Pathology and Forensic Medicine, Purine-Nucleoside Phosphorylase, Testicular Neoplasms, Biomarkers, Tumor, Humans, SOXD Transcription Factors, Ubiquitin Thiolesterase
Abstract

Malignant mesothelioma (MM) of the tunica vaginalis (TV) is a rare and aggressive tumour, and the molecular features and staining profile with contemporary immunohistochemical (IHC) biomarkers are largely unexplored. We characterise the clinicopathological, molecular and IHC features of MM (n = 13) and mesothelial neoplasms of uncertain malignant potential (MUMP) (n = 4).Targeted next-generation sequencing was performed on seven MMs and two MUMPs. IHC was performed for methylthioadenosine phosphorylase (MTAP), BRCA1-associated protein 1 (BAP1) and SRY-box transcription factor 6 (SOX6). Thirteen adenomatoid tumours were also assessed with SOX6. MM were epithelioid (seven of 13) or biphasic (six of 13). In MM, NF2 (five of seven; 71%), CDKN2A (three of seven; 43%) and BAP1 (two of seven; 29%) were most frequently altered. Non-recurrent driver events were identified in PTCH1 and TSC1. In contrast, none of these alterations were identified in MUMPs; however, one MUMP harboured a TRAF7 missense mutation. By IHC, loss of MTAP (two of 12; 17%) and BAP1 (two of nine; 22%) was infrequent in MM, whereas both were retained in the MUMPs. SOX6 was positive in nine of 11 (82%) MMs and negative in all MUMPs and adenomatoid tumours.Testicular MM exhibit a similar mutational profile to those of the pleura/peritoneum; however, alterations in CDKN2A and BAP1 are less common. These findings suggest that although MTAP and BAP1 IHC are specific for MM, their sensitivity in testicular MMs appears lower. In addition, rare tumours may harbour targetable alterations in driver genes (PTCH1 and TSC1) that are unusual in MMs at other anatomical sites. SOX6 is sensitive for MM; accordingly, the presence of SOX6 expression argues against a benign neoplastic process.

Published
2022

4. Severe recalcitrant otic lichen planus treated with mycophenolate mofetil

Author

Jennifer J. Shin, Joseph F. Merola, Stephanie Schulte, and Lisa N. Guo

Subjects
medicine.medical_specialty, lichen planus, business.industry, mycophenolate mofetil, LP, lichen planus, Case Report, otitis media, Dermatology, lcsh:RL1-803, Mycophenolate, otitis externa, LP - Lichen planus, lcsh:Dermatology, medicine, Humans, MMF, mycophenolate mofetil, Lichen, business
Published
2021
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5. Model-Independent Study of Structure in B+→D+D−K+ Decays

Author

L. Calefice, Julian Alexander Boelhauve, Marco Adinolfi, A. Fernandez Prieto, Emmy Gabriel, Benedetto Gianluca Siddi, Jascha Peter Grabowski, V. Shevchenko, Anna Danilina, Cedric Meaux, A. Petrolini, M. Patel, Anastasiia Kharisova, Federico Lazzari, N. K. Watson, S. Eidelman, Kevin Heijhoff, Lorenzo Capriotti, Yiheng Luo, Deepanwita Dutta, Stefano Petrucci, F. Blanc, G. Carboni, D. E. Hutchcroft, Pascal Vincent, Marcel Materok, Rizwaan Adeeb Mohammed, Vitalii Lisovskyi, Simon Stemmle, S. Playfer, Edoardo Franzoso, Frank Ferrari, James Mwangi Kariuki, R. Lefèvre, Marco Petruzzo, G. Graziani, Marian Stahl, David Gascon, Naomi Veronika Raab, Jana Crkovská, J. Lomba Castro, Da Yu Tou, F. Teubert, Igor Skiba, Yang Yang, Ivan Solovyev, W. Baldini, A. Lai, Andrea Mauri, Wenbin Qian, James Vincent Mead, F. Goncalves Abrantes, A. Jawahery, Thomas Peter Jones, Andrea Lampis, B. Fang, G. Valenti, W. Wislicki, C. Santamarina Rios, Titus Mombächer, Thomas Grammatico, Y. Gao, A. Alfonso Albero, G. Wormser, Kenenbek Arzymatov, O. Steinkamp, Guy Wilkinson, P. Vazquez Regueiro, D. De Simone, Viacheslav Matiunin, Yonghui Zhou, Marco Cattaneo, Daniel Vieira, Ming Zeng, Tommaso Pajero, Yawen Wang, Sebastian Neubert, Kuzma Ivshin, Joan Mauricio, Philipp Ibis, Jordy Sebastiaan Butter, Marcin Kucharczyk, Maximilien Chefdeville, M. van Veghel, G. Martellotti, Petr Fedin, Vladimir Chulikov, C. Haen, Artem Maevskiy, C. B. Van Hulse, Oleg Yushchenko, Xiao-yan Li, Olivier Deschamps, Niklas Stefan Nolte, Ying Lu, Mark Wilkinson, Roland Waldi, Razvan Daniel Moise, J. M. Yu, Agnieszka Oblakowska-Mucha, Martina Ferrillo, X. Han, Martha Hilton, F. Archilli, Cynthia Nunez, B. Malecki, M. Pepe Altarelli, Thomas Harrison, Edward James Millard, Marco Gersabeck, M. Vieites Diaz, D. R. Johnson, Maciej Witold Majewski, C. R. Jones, Matthew Scott Rudolph, W. D. Hulsbergen, J. A. Rodriguez Lopez, Sook Hyun Lee, M. J. Bradley, Gary Robertson, Sergey Gromov, Lucian Cojocariu, Mark Smith, M. Tobin, Krzysztof Swientek, Olga Madejczyk, Franco Bedeschi, P. Fernandez Declara, C. Vázquez Sierra, Lucio Anderlini, Chenxi Gu, Ina Carli, Nikita Kazeev, A. Casais Vidal, L. Meyer Garcia, B. Quintana, E. Santovetti, Tatiana Gaintseva, Stephen G. Weber, Richard Lane, Gediminas Sarpis, A. Brossa Gonzalo, P. Gironella Gironell, Tabitha Halewood-leagas, Zishuo Yang, M. Palutan, L. Dieste Maronas, M. O. Bettler, M. R. J. Williams, Naomi Cooke, L. Zhang, S. Ferreres Sole, I. V. Gorelov, K. Müller, Giovanni Bassi, Timon Schmelzer, Timofei Maltsev, J. Serrano, V. Gibson, R. Schwemmer, Mauro Morandin, Zhiyu Xiang, X. Cid Vidal, F. Muheim, John Gordon Smeaton, Guanghua Gong, Christopher John Parkinson, M. Veltri, G. Haefeli, Jennifer Clare Smallwood, L. Calero Diaz, Yuyue Gan, Anatoly Butkevich, Valery Pugatch, Vladimir Romanovskiy, A. Zhelezov, K. Carvalho Akiba, Aleksei Chernov, Xiaofeng Zhu, C. Remon Alepuz, A. Papanestis, Gaia Lanfranchi, A. Grecu, D. Sanchez Gonzalo, N. Tuning, John Matthew Durham, K. E. Kim, Amanda May Donohoe, William Parker, K. De Bruyn, Dana Bobulska, Violaine Bellee, William Dean, Alessandra Gioventù, Andrey Ustyuzhanin, G. Punzi, J. J. Back, M. Rotondo, Serhii Cholak, J. M. Otalora Goicochea, Piera Muzzetto, Wolfgang Funk, Matthew George Chapman, Marko Milovanovic, Emilie Maurice, F. Polci, Loris Martinazzoli, Markus Frank, Ao Xu, Mara Senghi Soares, Jakob Haimberger, J. García Pardiñas, D. Torres Machado, R. Lindner, Elisabeth Maria Niel, Davide Fazzini, Sonia Amina Bouchiba, T. Ruf, Y. Li, R. Silva Coutinho, Ryan Newcombe, Evgenii Shmanin, J. Maratas, Ifan Williams, Sergei Popov, Bernardo Adeva, Lex Marinus Greeven, Renata Kopecna, Andrea Merli, Jakub Ryzka, Timothy Evans, Jacopo Cerasoli, Dmitrii Maisuzenko, Hans Dijkstra, Bhagyashree Pagare, Alessandro Pastore, Zhenzi Wang, Veronica Soelund Kirsebom, Zan Ren, J. H. Lopes, Zhipeng Tang, Adam Dendek, B. Garcia Plana, Anastasia Smetkina, D. Martinez Santos, J. Z. Fan, Wenhua Hu, Y. Zhang, Youen Kang, S. Blusk, Saverio Mariani, Vukan Jevtic, Alessandro Camboni, K. M. Fischer, M.-N. Minard, A. Vorobyev, Marek Jezabek, F. Dordei, Martino Borsato, Mark Whitehead, P. Garcia Moreno, D. Zhang, J. J. Xu, Karlis Dreimanis, R. Calabrese, Sophie Elizabeth Hollitt, Lucas Mcconnell, Tommaso Colombo, Carmen Giugliano, Silvia Borghi, M. Karacson, Qundong Han, Basem Khanji, Y. Xie, Thomas Blake, H. Schindler, Marek Idzik, Thomas Hadavizadeh, Maxim Borisyak, C. Gaspar, Davide Brundu, Jing Wang, Colm Harold Murphy, Resmi P.K, Arnaud Robert, Hannah Louise Pullen, M. Korolev, J. He, Surapat Ek-In, Alex Pearce, C. Patrignani, V. Tisserand, M. Andreotti, Gennady Panshin, M. Poli Lener, M. van Beuzekom, X. Huang, Patrick Owen, Fabrice Desse, Alexander Semennikov, Kevin Heinicke, Fedor Baryshnikov, Christoph Langenbruch, Chung Nguyen-Mau, Kara Renee Mattioli, M. Cruz Torres, Gregory Ciezarek, Marcel Merk, Konrad Klimaszewski, Fidan Suljik, Sara Celani, Aravindhan Venkateswaran, Jia-Jia Qin, Anatoly Konoplyannikov, Scott Ely, Maria Elena Stramaglia, Giulia Frau, Lishuang Ma, C. Chen, M. De Cian, Hongjie Mu, Jonas Rademacker, Jozef Tomasz Borsuk, Stephen M. Stahl, Marie Bachmayer, N. Neufeld, Viacheslav Duk, C. Sanchez Mayordomo, Daniele Marangotto, Feng Jiang, Matthieu Marinangeli, S. J. Chen, Jacopo Pinzino, C. Sanchez Gras, Gianluigi Casse, Angelo Loi, S. Easo, Miroslaw Firlej, R. Santacesaria, Anna Ossowska, Nathan Jurik, Lain-Jong Li, Tamaki Holly Mcgrath, Giovanni Cavallero, Fionn Caitlin Ros Bishop, Stefano Zucchelli, E. Jans, Lauren Emma Yeomans, H. V. Cliff, Anthony Gavin Downes, Sofia Kotriakhova, Jeremy Dalseno, P. Griffith, Daniel Joachim Unverzagt, Srishti Bhasin, Guillaume Pietrzyk, Louis Henry, Paolo Ciambrone, Hilbrand Steffen Kuindersma, Danila Saranin, Tomasz Fiutowski, P. Collins, Y. Sun, Andrii Usachov, M. Rama, F. Fontanelli, Michele Veronesi, Zakariya Aliouche, Federico Alessio, Christoph Hasse, G. Passaleva, Christopher James Pawley, Christopher Burr, D. Vom Bruch, Julien Cogan, Artem Ryzhikov, P. Campana, Hongxi Xing, Nis Meinert, Shudong Zhang, Alison Tully, Michal Kreps, Sergey Strokov, L. M. Garcia Martin, Paolo Carniti, Meril Reboud, B. Jost, M. S. Rangel, Liupan An, R. Matev, B. Rachwal, Victor Egorychev, Alexander Berezhnoy, Hanna Malygina, Mikhail Mikhasenko, Andrea Bizzeti, Sara Sellam, G. Manca, Diego Alejandro Milanes, Paul Seyfert, M. J. Morello, P. Perret, William Barter, Martina Pili, Angelo Carbone, Mika Vesterinen, Ph. Charpentier, O. Schneider, Natalia Polukhina, Qiang Xu, Alexander Malinin, Gerwin Meier, S. Kandybei, J. A. B. Coelho, M. T. Tran, R. McNulty, P. Krokovny, Eduardo Rodrigues, M. Senghi Soares, Sergey Barsuk, M. Xu, Cameron Thomas Dean, B. Souza De Paula, R. Vazquez Gomez, H. W. Van Hecke, Oliver Lantwin, Michal Dziewiecki, Karol Hennessy, N. Valls Canudas, M. Brodski, François Fleuret, Jaap Velthuis, B. Leverington, D. Yang, E. Grauges, M. Chrzaszcz, L. Giubega, A. Oyanguren, T. Kirn, Stephane T'Jampens, Vlad-Mihai Placinta, Jennifer Brigitta Zonneveld, I. A. Monroy, R. Nandakumar, F. Machefert, Tai-hua Lin, Olli Lupton, L. G. Scantlebury Smead, M. Charles, A. B. Rodrigues, P. Alvarez Cartelle, Marco Clemencic, Luyan Sun, Mikkel Bjørn, K. Wyllie, F. A. Garcia Rosales, Lars Eklund, B. Pietrzyk, Mark Slater, Vladislav Belavin, E. Spadaro Norella, Cheryl Pappenheimer, Y. H. Zheng, Eliane Epple, Florian Reiss, S. Malde, Jonas Nathanael Eschle, L. Tomassetti, Adam Szabelski, V. V. Gligorov, C. Marin Benito, Tatiana Ovsiannikova, Nikolai Voropaev, David Anthony Friday, A. Ukleja, Yue Pan, T. J. Gershon, C. J. G. Onderwater, Alexander Inglessi, A. G. Morris, Stefano Cali, George Coombs, E. van Herwijnen, Elena Graverini, T. E. Latham, L. Shekhtman, Maciej Pawel Szymanski, Jiangqiao Hu, A. Dziurda, Elie Aslanides, Roger Forty, Alexander Battig, Xixin Liang, Gabriele Simi, Lukas Witola, Artur Ishteev, C. Parkes, Silvia Gambetta, Ziad Ajaltouni, Valeriia Lukashenko, Arthur Marius Hennequin, Heather Mckenzie Wark, S. Perazzini, M. Franco Sevilla, Dmitry Popov, Simon Akar, E. Ben-Haim, Maxime Schubiger, Anton Philippov, Nicola Serra, H. B. Liu, A. Bay, Abbie Jane Chadwick, Matthieu Kecke, Flavio Pisani, B. T. Meadows, Antonio Pellegrino, Alexey A. Petrov, Joseph David Shupperd, F. Redi, R. Graciani Diaz, Halime Sazak, Andrew Beiter, Alexandre Boyer, Claire Prouve, Neville Harnew, G. Raven, D. Decamp, A. Golutvin, A. F. Campoverde Quezada, E. Polycarpo, Tatsuya Nakada, Marco Guarise, Vladislav Balagura, F. Stagni, Victor Coco, Zhuoming Li, Phoebe Meredith Hamilton, Jan Buytaert, P. Spradlin, Ignacio Bediaga, Desmond Mzamo Shangase, M. D. Sokoloff, U. Marconi, F. F. Wilson, Lingzhu Bian, A. Gomes, Federico Betti, L. A. Granado Cardoso, S. Meloni, Ilia Belov, G. Bencivenni, S. Esen, Wojciech Kucewicz, Gianluca Zunica, Michele Atzeni, G. Mancinelli, Conor Fitzpatrick, Antonino Sergi, T. Boettcher, M. Plo Casasus, Mateusz Goncerz, Barbara Sciascia, Stephanie Schulte, Sergey Didenko, Simone Bifani, S. Farry, W. Huang, M. Mukherjee, Ryan Calladine, Plamen Hristov Hopchev, Francesco Dettori, A. Brea Rodriguez, Dmitrii Ilin, Yanting Fan, Maria Flavia Cicala, Petr Andreevich Gorbounov, Jordan Daniel Roth, Michele Piero Blago, Hossein Afsharnia, G. Liu, Marco Santimaria, D. Websdale, B. Couturier, R. A. Fini, Daniel Berninghoff, A. Falabella, M. Sarpis, Biagio Saitta, Stanislav Luchuk, L. R. Madhan Mohan, Lesya Shchutska, D. Campora Perez, Moran Wang, Carmelo D'Ambrosio, Jean François Marchand, V. Kudryavtsev, D. R. Ward, Oleg Stenyakin, S. Tolk, Donal Murray, E. Cogneras, Emilie Bertholet, Peilian Li, Xiao-Rui Lyu, E. Dall’Occo, E. Golobardes, Jonathan Plews, R. Currie, C. Abellán Beteta, S. Capelli, P. De Simone, S. Hansmann-Menzemer, Gerd Joachim Kunde, A. Schopper, L. De Paula, Baasansuren Batsukh, Zhihong Shen, S. Schael, Marianna Fontana, Luca Minzoni, Dylan Jaide White, Michela Garau, S. A. Wotton, Patrick Robbe, P. Baladron Rodriguez, John Jake Lane, K. Petridis, Serhii Koliiev, Rudolf Oldeman, C. A. Aidala, L. Del Buono, Roman Litvinov, Ilaria Neri, F. J. P. Soler, Niladribihari Sahoo, A. Tsaregorodtsev, Oleksander Kot, Xia-Ji Liu, Sheldon Stone, S. C. Haines, A. Hicheur, Felix Johannes Kress, Shantam Taneja, B. Spaan, J. Closier, A. Massafferri, Philipp Roloff, Alexandra Paige Rollings, John Leslie Cobbledick, Roel Aaij, Vadym Denysenko, M. De Serio, D. Lacarrere, C. L. Da Silva, R. Mountain, Claudia Bertella, Murdo Traill, Rui Wang, Aleksandra Snoch, S. Vecchi, Quentin Fuehring, Phillip John Marshall, A. Gallas Torreira, Wojciech Krzemien, Tobias Tekampe, M. McCann, Carina Trippl, Dawid Gerstel, Eluned Smith, Hangyi Wu, Lucia Grillo, Aleksandr Solovev, C. Matteuzzi, Andreas Güth, Margarete Schellenberg, Peter Svihra, T. D. Nguyen, T. Lesiak, C. A. Chavez Barajas, A. McNab, Roland Bernet, Ross John Hunter, Alessio Piucci, Holger Stevens, Hang Yin, O. Boente Garcia, Robbert Erik Geertsema, Evelina Gersabeck, Barbara Passalacqua, Samuel Belin, Mauro Piccini, Benjamin Audurier, Malte Hecker, Denis Derkach, F. Ferreira Rodrigues, Renato Quagliani, Dmitrii Pereima, Fedor Ratnikov, Yasmine Amhis, Gabriela Johanna Pomery, Michael Becker, Dmitry Golubkov, Matteo Giovannetti, Alexander D. Popov, Alexey Boldyrev, M. H. Schune, C. Göbel, O. Maev, Giulia Tuci, Abhijit Mathad, Almagul Kondybayeva, A. Romero Vidal, Constantin Weisser, Sergey Legotin, D. Hynds, D. Galli, Marina Artuso, Salvatore Aiola, Philip Ilten, L. Garrido, H. Li, Tomasz Skwarnicki, Davide Zuliani, Patrick Mackowiak, U. Uwer, Sebastian Bachmann, V. Obraztsov, Jakub Moron, Sergei Kholodenko, Kodassery Prasanth, Hans Dembinski, Roberta Cardinale, Roberto Ribatti, M. Shapkin, Floris Keizer, D. Pinci, Jihyun Bhom, Mariia Poliakova, E. Vilella Figueras, L. Ferreira Lopes, Simon Baker, M. Lucio Martinez, Stephan Eisenhardt, Liliana Congedo, F. L. Souza De Almeida, Brij Kishor Jashal, Lorenzo Pica, Pavol Stefko, A. Palano, Tomasz Szumlak, Lukas Gruber, R. Le Gac, V. Franco Lima, Alexandru Ene, E. Thomas, Ivan Polyakov, F. Maciuc, Tara Shears, S.-G. Chitic, Adam Benjamin Morris, J. A. de Vries, Georgios Chatzikonstantinidis, S. Filippov, Samuel Maddrell-Mander, P. Naik, Mauricio Féo, R. Jacobsson, Rafal Dominik Krawczyk, P. Gandini, Matthew James Tilley, Matteo Bartolini, Nathanael Farley, M. Witek, M. Needham, Matthew Birch, Igor Kostiuk, L. Kravchuk, Alessandro Cardini, Chishuai Wang, J. M. De Miranda, Anton Poluektov, Lorenzo Sestini, E. Govorkova, Harald Viemann, Alexander Leflat, M. Mulder, A. Bursche, S. Ricciardi, V. Vorobyev, M. Romero Lamas, M. Ferro-Luzzi, I. Longstaff, L. L. Pappalardo, P. Camargo Magalhaes, Adam Davis, Aleksei Andreianov, N. Sagidova, O. Zenaiev, F. Martinez Vidal, Tjeerd Ketel, R. I. Rabadan Trejo, Sune Jakobsen, Konstantin Gizdov, Wiktor Byczynski, M. Martinelli, J. Baptista Leite, Ouail Kitouni, Johannes Albrecht, Dominik Stefan Mitzel, Gianfranco Morello, Pawel Kopciewicz, Claudio Gotti, Blaise Delaney, Laura Promberger, Christoph Frei, P. Billoir, Malcolm John, M. Gandelman, Victor Renaudin, Pietro Marino, M. Schmelling, J. Fu, Sandra Amato, A. Bondar, Vladimir Macko, I. Nasteva, Dominik Müller, V. Vagnoni, Yury Guz, Alessio Sarti, M. Fiorini, E. Gushchin, Andrea Valassi, Tara Nanut, K. Belous, Jolanta Brodzicka, Dong Xiao, Biljana Mitreska, Matthew Kenzie, Zehua Xu, Daria Strekalina, E. Luppi, A. Bertolin, Shuaiyi Liu, Mark Hatch, Xavier Vilasis-Cardona, Laurent Dufour, Nicola Neri, C. M. Costa Sobral, Johannes Heuel, Sara Elizabeth Mitchell, A. Dovbnya, J. J. Walsh, Davide Lancierini, Daniel Patrick O'Hanlon, Z. Mathe, Veronika Chobanova, Nikolay Bondar, Jan Langer, M. Pappagallo, Ph. Ghez, A. Sciubba, Paul Andre Günther, O. De Aguiar Francisco, Miroslav Saur, Tengiz Kvaratskheliya, Paul Nathaniel Swallow, A. Lusiani, B. R. Gruberg Cazon, J. Marks, Antje Mödden, M. Straticiuc, Yuezhe Yao, Huacheng Cai, G. D. Lafferty, T. Gys, Ivan Shchemerov, Preema Rennee Pais, Ekaterina Trifonova, l. Soares Lavra, P. Di Nezza, S. Klaver, J. J. Saborido Silva, Anna Lupato, S. Monteil, George Holger Lovell, R. Manera Escalero, Manuel Schiller, Lauren Douglas, Biplab Dey, Serena Maccolini, Wojciech Krupa, Alexsei Chubykin, Simon Nieswand, Annarita Buonaura, Valery Zhukov, J. M. Fernandez-tenllado Arribas, S. Simone, Christopher Betancourt, A. Satta, Ulrik Egede, Svende Braun, C. Satriano, A. Contu, Olivier Leroy, Polina Kravchenko, Harris Conan Bernstein, C. Bozzi, A. Puig Navarro, R. J. Barlow, E. L. Gkougkousis, Marta Calvi, B. Schmidt, Ivan Belyaev, Jan-Marc Basels, A. Artamonov, Michal Kazimierz Mazurek, D. Wiedner, A. Dzyuba, Guillermo Loustau, D. Hill, Li Xu, S. De Capua, Ia. Bezshyiko, Nikolay Nikitin, S. Gomez Fernandez, Daniel Stephen Richards, D. Savrina, Philippe d'Argent, P. E. L. Clarke, Sebastien Ponce, Kayleigh Anne Thomson, Daniele Manuzzi, A. C. dos Reis, G. Alkhazov, Mikhail Hushchyn, Xuhao Yuan, Jiayin Sun, Sophie Katharina Kretzschmar, M. Calvo Gomez, Maciej Wojciech Dudek, E. B. Shields, G. Corti, Martin Stefan Bieker, Daniel Charles Craik, M. Ramos Pernas, P. Durante, Giacomo Vitali, Louis Lenard Gerken, Stephan Escher, Patrick Koppenburg, B. D. C. Westhenry, Sandro Cadeddu, D. Melnychuk, X. J. Zhou, Thomas Ackernley, A. Vollhardt, Kristian Alexander Zarebski, Michael Alexander, D. Lucchesi, Thomas Henry Hancock, Alex Seuthe, Mark Richard James Williams, Mikhail Zavertyaev, Nicola Skidmore, Vasyl Dobishuk, Themistocles Bowcock, Stanislav Poslavskii, David Gerick, J. Ruiz Vidal, Kurt Rinnert, Milosz Zdybal, and Alexander Vagner

Subjects
Physics, Particle physics, Large Hadron Collider, 0103 physical sciences, Structure (category theory), General Physics and Astronomy, High Energy Physics::Experiment, Nuclear Experiment, 010306 general physics, 01 natural sciences, Luminosity
Abstract

The only anticipated resonant contributions to $B^+\to D^+D^-K^+$ decays are charmonium states in the $D^+D^-$ channel. A model-independent analysis, using LHCb proton-proton collision data taken at centre-of-mass energies of $\sqrt{s}=7,8,$ and $13$ TeV, corresponding to a total integrated luminosity of 9 fb$^{-1}$, is carried out to test this hypothesis. The description of the data assuming that resonances only manifest in decays to the $D^+D^-$ pair is shown to be incomplete. This constitutes evidence for a new contribution to the decay, potentially one or more new charm-strange resonances in the $D^-K^+$ channel with masses around 2.9 GeV$/c^2$.

Published
2020
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6. Search for Lepton-Universality Violation in B+→K+ℓ+ℓ− Decays

Author

Samuel Belin, Arseniy Vitkovskiy, Carmelo D'Ambrosio, Jean François Marchand, Oleg Stenyakin, Mark Wilkinson, Roland Waldi, C. Fitzpatrick, C. A. Aidala, Lukas Gruber, A. Romero Vidal, Constantin Weisser, H. Li, Timofei Maltsev, J. Serrano, L. Del Buono, R. Le Gac, V. Franco Lima, Zan Ren, Matthew Charles, Hannah Louise Pullen, G. Valenti, Ryan Calladine, Plamen Hristov Hopchev, Feng Jiang, Matthieu Marinangeli, Floris Keizer, Matthew James Tilley, Nathanael Farley, Igor Kostiuk, M. Witek, J. He, Yang Li, S. J. Chen, Jacopo Pinzino, Wen Chao Zhang, Kuzma Ivshin, Murdo Traill, C. Sanchez Gras, Konstantin Gizdov, Wiktor Byczynski, E. Cogneras, G. Mancinelli, S. Easo, Miroslaw Firlej, M. Needham, Antonino Sergi, Anna Ossowska, Nathan Jurik, P. Billoir, D. Lucchesi, Philipp Ibis, Lauren Emma Yeomans, T. Boettcher, S. A. Wotton, Rudolf Oldeman, P. Campana, Hongxi Xing, Paolo Carniti, William Barter, Martina Pili, Meril Reboud, Oliver Lupton, Johannes Albrecht, Angelo Carbone, Jaap Velthuis, S. Eidelman, Malcolm John, Matthew Kelsey, Jordy Sebastiaan Butter, A. Gallas Torreira, R. Schwemmer, Nicoletta Belloli, Renato Quagliani, M. Gandelman, C. Sanchez Mayordomo, H. V. Cliff, Alexander Berezhnoy, D. Websdale, L. M. Garcia Martin, B. Couturier, Mick Mulder, Federico Alessio, Mark Slater, Marcin Kucharczyk, Maximilien Chefdeville, M. Patel, R. Hidalgo Charman, Anastasiia Kharisova, Michael Sokoloff, N. K. Watson, Varvara Batozskaya, V. Volkov, F. Blanc, R. A. Fini, Marie Helene Schune, E. Gushchin, D. Tonelli, C. Göbel, J. E. Andrews, Vladimir Macko, I. Nasteva, C. Abellán Beteta, Margarita Stepanova, Florian Reiss, S. Malde, A. Dovbnya, D. R. Johnson, Z. C. Huard, R. Lefèvre, J. J. Walsh, Davide Lancierini, Daniel Patrick O'Hanlon, B. Souza De Paula, James Vincent Mead, Marco Adinolfi, Christopher Parkes, Maciej Witold Majewski, G. D. Lafferty, S. Schael, David Loh, T. Skwarnicki, U. Egede, P. Durante, A. Fernandez Prieto, Emmy Gabriel, Benedetto Gianluca Siddi, Jascha Peter Grabowski, V. Shevchenko, Yiheng Luo, A. Di Canto, L. Ferreira Lopes, X. Cid Vidal, F. Muheim, E. Ben-Haim, Maxime Schubiger, Jonas Rademacker, Emanuele Michielin, Deepanwita Dutta, A. Tsaregorodtsev, G. Graziani, Sarah Beranek, C. R. Jones, Matthew Scott Rudolph, M. Ravonel Salzgeber, Stephan Escher, Stefano Petrucci, David Gascon, T. E. Latham, Nikita Kazeev, P. Vazquez Regueiro, B. Hamilton, L. Shekhtman, Jiangqiao Hu, A. Dosil Suárez, Xixin Liang, Frederic Machefert, Sheldon Stone, Sean Benson, S. Filippov, Kenenbek Arzymatov, John Gordon Smeaton, M. Veltri, G. Haefeli, Alexander Inyakin, Cameron Thomas Dean, Ignacio Bediaga, G. Tellarini, Viacheslav Matiunin, Mark Hatch, C. M. Costa Sobral, C. Hadjivasiliou, Xianglei Zhu, Johannes Heuel, Patrick Koppenburg, U. Straumann, Lei Zhang, Marco Cattaneo, Xiao-yan Li, G. Cavallero, Elena Graverini, O. Steinkamp, Daniel Vieira, Qiang Xu, C. Bozzi, V. Vorobyev, M. Ferro-Luzzi, L. L. Pappalardo, M. T. Tran, Victor Coco, M. Vieites Diaz, Olivier Deschamps, Niklas Stefan Nolte, Alexander Baranov, Flavio Archilli, Yuezhe Yao, Huacheng Cai, Markus Frank, E. Spadaro Norella, Andrew Crocombe, Z. Mathe, Zhuoming Li, Stephen M. Stahl, Yuyue Gan, Albert Comerma-Montells, Federico Cindolo, Roger Forty, A. Puig Navarro, Veronika Chobanova, N. Neufeld, C. Marin Benito, Dmitry Popov, Simon Akar, W. Huang, Sandro Cadeddu, Nikolay Bondar, Lucio Anderlini, Alexander Battig, Stephanie Schulte, Sergey Didenko, I. A. Monroy, S. Esen, Roman Greim, Wojciech Kucewicz, Simone Bifani, M. Mukherjee, D. Melnychuk, M. van Veghel, Giulio Gazzoni, Nikolai Voropaev, M. Shapkin, l. Soares Lavra, R. J. Barlow, Gediminas Sarpis, S. Roiser, Yu. Guz, F. Stagni, Giulio Dujany, Jonathan Plews, D. Campora Perez, Marta Calvi, Miroslav Saur, Ph. Ghez, A. Sciubba, V. Kudryavtsev, J. D. Osborn, D. R. Ward, Donal Murray, Anna Lupato, Tengiz Kvaratskheliya, Jan Buytaert, Karlis Dreimanis, R. Calabrese, Ming Zeng, Tommaso Pajero, R. Cenci, M. Plo Casasus, Sebastian Neubert, I. Longstaff, P. De Simone, Valery Pugatch, S. Monteil, Sofia Kotriakhova, Matthieu Kecke, C. Gaspar, George Holger Lovell, Jing Wang, F. Martinez Vidal, A. Bay, Wouter Hulsbergen, Marco Santimaria, N. Tuning, Violaine Bellee, M. Brodski, B. R. Gruberg Cazon, Tjeerd Ketel, William Dean, Vladimir Romanovskiy, A. Zhelezov, B. Schmidt, A. Lusiani, O. De Aguiar Francisco, B. Sanmartin Sedes, Lucian Cojocariu, J. Marks, Antje Mödden, Alex Pearce, Mark Smith, Ivan Belyaev, T. Gys, R. Niet, M. Straticiuc, G. A. Cowan, Martha Hilton, R. Nandakumar, Pietro Albicocco, Manuel Schiller, B. Spaan, Daniele Marangotto, Lauren Douglas, R. Currie, Elie Aslanides, Mauricio Féo, A. Vollhardt, Moritz Demmer, A. Bertolin, Barbara Sciascia, J. Closier, A. Massafferri, J. Fu, S. Hansmann-Menzemer, Gerd Joachim Kunde, A. Artamonov, Jordan Daniel Roth, M. Rotondo, G. Manca, O. Schneider, Natalia Polukhina, Wojciech Krupa, P. Di Nezza, S. Klaver, M. Boubdir, Kristian Alexander Zarebski, Michael Alexander, Thomas Henry Hancock, Nicola Serra, J. Jalocha, B. Malecki, M. Vernet, M. Xu, J. J. Saborido Silva, Renata Kopecna, Vincenzo Battista, S. Perazzini, Alexey A. Petrov, A. Schopper, M. Heß, Nis Meinert, Michal Kreps, Sergey Strokov, B. Jost, Louis Henry, Andrea Valassi, Tara Nanut, J. Garra Tico, Guido Andreassi, Agnieszka Oblakowska-Mucha, Roel Aaij, Jakub Moron, Hanna Malygina, Alison Tully, Mohamad Kozeiha, G. Tuci, B. T. Meadows, Andrew Beiter, Pietro Marino, M. Schmelling, Dong Xiao, U. Marconi, J. Arnau Romeu, Tomasz Fiutowski, Alex Seuthe, Iwan Thomas Smith, Karol Hennessy, Sebastien Valat, Nikita Beliy, E. S. Sepulveda, S. Farry, Brij Kishor Jashal, A. Palano, Tomasz Szumlak, Alexander Vagner, G. Raven, D. Decamp, A. Golutvin, Anna Danilina, Cedric Meaux, P. Collins, Y. Sun, C. Lazzeroni, Alexander Semennikov, C. Remon Alepuz, T. Lesiak, Tatiana Ovsiannikova, J. M. Otalora Goicochea, Wolfgang Funk, Mark Richard James Williams, Mikhail Zavertyaev, Matthew George Chapman, Emilie Maurice, X. Han, Andreas Weiden, Nicola Skidmore, Janine Müller, Biplab Dey, Slavomira Stefkova, S. Kandybei, J. A. B. Coelho, S. Ogilvy, Martino Borsato, A. Papanestis, M. Dorigo, T. Kirn, Christian Färber, P. R. Li, A. Dziurda, R. Graciani Diaz, M. Tobin, H. W. Van Hecke, Marco Clemencic, Luyan Sun, Mikkel Bjørn, Kevin Heinicke, Heather Mckenzie Wark, E. Dall'Occo, Alexandru Ene, Krzysztof Swientek, E. Thomas, Florian Lemaitre, Franco Bedeschi, Matteo Bartolini, P. Fernandez Declara, K. De Bruyn, Timon Schmelzer, Claire Prouve, Zehua Xu, Neville Harnew, Maciej Pawel Szymanski, Flavio Pisani, L. Kravchuk, C. Vázquez Sierra, Chenxi Gu, K. Carvalho Akiba, Alessandro Cardini, Alexsei Chubykin, Xavier Vilasis-Cardona, M. Winn, Themistocles Bowcock, E. Tournefier, Stanislav Poslavskii, S. Ferreres Sole, A. Dzyuba, Guillermo Loustau, Xuesong Liu, V. Gibson, K. E. Kim, William Parker, F. Polci, Mike Williams, Vitalii Lisovskyi, Dmitry Golubkov, Davide Fazzini, David Gerick, J. Ruiz Vidal, A. Petrolini, Marco Petruzzo, Matthew Kenzie, Marian Stahl, L. De Paula, Baasansuren Batsukh, Felix Johannes Kress, Federica Lionetto, S.-G. Chitic, Adam Benjamin Morris, Georgios Chatzikonstantinidis, Samuel Maddrell-Mander, J. M. De Miranda, B. Quintana, V. Bocci, A. Bursche, Naomi Veronika Raab, J. Maratas, Ifan Williams, Aravindhan Venkateswaran, Patrick Mackowiak, M. Pepe Altarelli, Thomas Harrison, Edward James Millard, Marco Gersabeck, Da Yu Tou, F. Teubert, D. Zhang, N. Neri, Jia-Jia Qin, I. V. Gorelov, K. Müller, R. Tourinho Jadallah Aoude, Simon Stemmle, S. Playfer, Kurt Rinnert, D. Pinci, Jihyun Bhom, Dominik Stefan Mitzel, H. F. Schreiner, A. Grecu, Andrey Ustyuzhanin, J. J. Back, Bernardo Adeva, F. F. Wilson, R. Jacobsson, Kara Renee Mattioli, Gianfranco Morello, Preema Rennee Pais, M. Cruz Torres, E. Santovetti, Claudio Gotti, Frank Ferrari, V. Salustino Guimaraes, James Mwangi Kariuki, Olivier Göran Girard, S. Gallorini, A. Gomes, Federico Betti, Mariia Poliakova, Simon Baker, G. Carboni, Marianna Fontana, F. J. P. Soler, U. Eitschberger, L. A. Granado Cardoso, Dominik Müller, Balazs Voneki, Alessandro Pastore, Zhenzi Wang, Veronica Soelund Kirsebom, Emma Buchanan, John Matthew Durham, T. Ruf, Patrick Owen, E. van Herwijnen, R. Ekelhof, Vladimir Gligorov, Michael Kolpin, G. Lanfranchi, M.-N. Minard, S. Stracka, V. Vagnoni, E. Luppi, Timothy Evans, Alex Birnkraut, D. E. Hutchcroft, S. Ricciardi, Marcel Materok, S. C. Haines, Christoph Frei, A. Hicheur, Guy Wilkinson, J. H. Lopes, Zhipeng Tang, Wenhua Hu, Y. Zhang, Malgorzata Pikies, Thibaud Humair, Andrea Merli, M. De Serio, D. Lacarrere, Patrick Robbe, Dmitrii Maisuzenko, S. Blusk, L. Tomassetti, M. Ramos Pernas, Alessandro Camboni, Fedor Baryshnikov, Hans Dijkstra, Maxim Borisyak, Stefano Zucchelli, Chung Nguyen-Mau, C. L. Da Silva, Gregory Ciezarek, A. A. Alves, A. Vorobyev, F. Dordei, Lucia Grillo, C. Matteuzzi, Giovanni Passaleva, Adam Szabelski, A. Ukleja, Kevin Maguire, C. Haen, Jeremy Dalseno, Phillip John Marshall, A. McNab, Igor Skiba, Roland Bernet, P. Griffith, R. Dzhelyadin, A. Lai, Andrea Mauri, Wenbin Qian, Paolo Ciambrone, C. B. Van Hulse, Achille Stocchi, Christoph Hasse, V. Chekalina, Oleg Yushchenko, Andrea Bizzeti, Wojciech Krzemien, Sune Jakobsen, Christopher Burr, J. V. Viana Barbosa, D. Vom Bruch, Ao Xu, Mara Senghi Soares, J. García Pardiñas, Zishuo Yang, M. Palutan, Tommaso Colombo, Antonio Pellegrino, M. O. Bettler, Timothy Gershon, Gianni Penso, Dana Bobulska, Basem Khanji, Y. Xie, Thomas Blake, E. Grauges, Evelina Gersabeck, F. Redi, H. Schindler, Marek Idzik, R. Lindner, Thomas Hadavizadeh, Davide Brundu, Colm Harold Murphy, Arnaud Robert, M. van Beuzekom, Benjamin Audurier, Denis Derkach, Silvia Gambetta, E. Polycarpo, Tatsuya Nakada, F. Ferreira Rodrigues, Scott Ely, Maria Elena Stramaglia, Marcela Vitti, Ph. Charpentier, G. Bencivenni, Alexander Malinin, C. Patrignani, Y. N. Gao, Markus Roehrken, V. Tisserand, M. Andreotti, Michele Atzeni, Samuel Coquereau, Adam Dendek, B. Garcia Plana, A. B. Rodrigues, D. Martinez Santos, G. Liu, Stefano Cali, Thomas N. Williams, Francesco Dettori, Mark Whitehead, Moran Wang, A. Falabella, S. Tolk, S. Karodia, Konrad Klimaszewski, Biagio Saitta, Dmitrii Pereima, Serhii Koliiev, Fedor Ratnikov, J. van Tilburg, Guillaume Pietrzyk, Alexandra Paige Rollings, G. Simi, S. Vecchi, Christoph Langenbruch, Gianluigi Casse, Angelo Loi, Andrii Usachov, Marco Pappagallo, Philip Ilten, Alessio Piucci, Yasmine Amhis, E. Jans, Srishti Bhasin, M. S. Rangel, Liupan An, Paul Seyfert, Gabriela Johanna Pomery, Stefanie Reichert, M. Morandin, Diego Alejandro Milanes, M. J. Morello, P. Perret, Sergey Barsuk, C. Joram, Roberta Cardinale, François Fleuret, B. Leverington, L. Giubega, A. Oyanguren, U. Uwer, Lorenzo Capriotti, Marcin Chrzaszcz, A. Jawahery, Razvan Daniel Moise, Mika Vesterinen, J. M. Yu, Stephane T'Jampens, Vlad-Mihai Placinta, Jennifer Brigitta Zonneveld, R. Silva Coutinho, Ryan Newcombe, Evgenii Shmanin, Silvia Borghi, A. Trisovic, M. Karacson, Qundong Han, Svende Braun, Eugenia Price, C. Chen, M. De Cian, M. Rama, F. Fontanelli, Michele Veronesi, D. Hill, Maurizio Martinelli, Andrea Mogini, S. De Capua, Ia. Bezshyiko, Nikolay Nikitin, D. Savrina, P. E. L. Clarke, R. Vazquez Gomez, Sebastien Ponce, A. C. dos Reis, Paras Naik, Lennaert Bel, G. Alkhazov, Michael McCann, Mikhail Hushchyn, R. Santacesaria, O. Maev, Abhijit Mathad, Xuhao Yuan, Jiayin Sun, Julien Cogan, Sebastian Bachmann, R. Matev, B. Rachwal, Victor Egorychev, Sophie Katharina Kretzschmar, M. Calvo Gomez, V. Obraztsov, M. Lucio Martinez, Stephan Eisenhardt, R. McNulty, P. Krokovny, G. Corti, Martin Stefan Bieker, Eduardo Rodrigues, Michal Dziewiecki, K. Wyllie, Simon Nieswand, B. Pietrzyk, Annarita Buonaura, Valery Zhukov, Ivan Polyakov, Daniel Charles Craik, F. Maciuc, S. Simone, Christopher Betancourt, A. Satta, M. Merk, Y. H. Zheng, C. J. G. Onderwater, Alexander Inglessi, J. A. de Vries, C. Satriano, A. Contu, Daniel Berninghoff, Olivier Leroy, A. Heister, H.-P. Dembinski, Luca Minzoni, Vladislav Balagura, Y. Wang, P. Spradlin, Holger Stevens, Hang Yin, O. Boente Garcia, Brice Maurin, Alexander D. Popov, Lars Eklund, Vanessa Müller, Tara Shears, Ziad Ajaltouni, L. Silva de Oliveira, Anton Poluektov, Lorenzo Sestini, Anita Nandi, E. Govorkova, Harald Viemann, Alexander Leflat, Blaise Delaney, Alessio Sarti, M. Fiorini, P. d'Argent, Michele Piero Blago, R. Mountain, Andreas Güth, Margarete Schellenberg, A. Alfonso Albero, G. Wormser, T. D. Nguyen, N. Sagidova, G. Punzi, Gennady Panshin, M. Poli Lener, Fabrice Desse, W. Wislicki, George Coombs, C. Khurewathanakul, C. Santamarina Rios, Titus Mombächer, G. Martellotti, L. Garrido, Pavol Stefko, Axel Kevin Kuonen, P. Gandini, Konstantinos Petridis, J. A. Rodriguez Lopez, Luca Pescatore, Adam Davis, Wander Baldini, Victor Renaudin, P. Alvarez Cartelle, Sandra Amato, A. Bondar, K. Belous, Jolanta Brodzicka, A. Brossa Gonzalo, P. Gironella Gironell, Tatiana Likhomanenko, Laurent Dufour, Emilie Bertholet, Xiao-Rui Lyu, Tobias Tekampe, Dawid Gerstel, Eluned Smith, Sophie Richards, Malte Hecker, D. Hynds, D. Galli, and Marina Artuso

Subjects
Physics, Particle physics, Large Hadron Collider, 0103 physical sciences, General Physics and Astronomy, 010306 general physics, 01 natural sciences, Lepton, Universality (dynamical systems)
Abstract

A measurement of the ratio of branching fractions of the decays B + → K + μ + μ − and B + → K + e + e − is presented. The proton-proton collision data used correspond to an integrated luminosity of 5.0 fb − 1 recorded with the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV. For the dilepton mass-squared range 1.1 < q 2 < 6.0 GeV 2 / c 4 the ratio of branching fractions is measured to be R K = 0.84 6 + 0.060 − 0.054 + 0.016 − 0.014 , where the first uncertainty is statistical and the second systematic. This is the most precise measurement of R K to date and is compatible with the standard model at the level of 2.5 standard deviations.

Published
2019
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7. The time course of neurolinguistic and neuropsychological symptoms in three cases of logopenic primary progressive aphasia

Author

Martina Minnerop, Katrin Amunts, Ferdinand Binkofski, Stephanie Schulte, Walter Huber, Marion Grande, Yosef Grodzinsky, Stefan Heim, Peter Pieperhoff, Louise Etcheverry, Martin Südmeyer, and Barbara Seidel

Subjects
Male, Longitudinal study, medicine.medical_specialty, Time Factors, Cognitive Neuroscience, Experimental and Cognitive Psychology, Audiology, Verbal learning, Apraxia, Speech Disorders, Developmental psychology, Primary progressive aphasia, Behavioral Neuroscience, Aphasia, medicine, Humans, Dementia, Attention, Longitudinal Studies, Aged, Psychiatric Status Rating Scales, Neuropsychology, Linguistics, Cognition, Middle Aged, Verbal Learning, medicine.disease, Aphasia, Primary Progressive, Disease Progression, Female, medicine.symptom, Cognition Disorders, Comprehension, Psychology, Psychomotor Performance
Abstract

Primary progressive aphasia (PPA) is a rare clinical dementia syndrome affecting predominantly language abilities. Word-finding difficulties and comprehension deficits despite relatively preserved cognitive functions are characteristic symptoms during the first two years, and distinguish PPA from other dementia types like Alzheimer's disease. However, the dynamics of changes in language and non-linguistic abilities are not well understood. Most studies on progression used cross-sectional designs, which provide only limited insight into the course of the disease. Here we report the results of a longitudinal study in three cases of logopenic PPA over a period of 18 months, with exemplary longitudinal data from one patient even over 46 months. A comprehensive battery of neurolinguistic and neuropsychological tests was applied four times at intervals of six months. Over this period, deterioration of verbal abilities such as picture naming, story retelling, and semantic word recall was found, and the individual decline was quantified and compared between the three patients. Furthermore, decrease in non-verbal skills such as divided attention and increasing apraxia was observed in all three patients. In addition, inter-subject variability in the progression with different focuses was observed, with one patient developing a non-fluent PPA variant. The longitudinal, multivariate investigation of logopenic PPA thus provides novel insights into the progressive deterioration of verbal as well as non-verbal abilities. These deficits may further interact and thus form a multi-causal basis for the patients' problems in every-day life which need to be considered when planning individually targeted intervention in PPA.

Published
2012
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8. Genetically Programmed Biases in Th1 and Th2 Immune Responses Modulate Atherogenesis

Author

Peter Libby, Galina K. Sukhova, and Stephanie Schulte

Subjects
CD4-Positive T-Lymphocytes, medicine.medical_specialty, Lymphocyte Activation, Collagen Type I, Pathology and Forensic Medicine, Cholesterol, Dietary, Mice, Apolipoproteins E, Th2 Cells, Immune system, Species Specificity, Antigen, Internal medicine, medicine, Animals, Serum amyloid A, Cells, Cultured, Mice, Knockout, Mice, Inbred BALB C, Serum Amyloid A Protein, Innate immune system, biology, Interleukin-6, Acute-phase protein, Interleukin, Th1 Cells, Atherosclerosis, Acquired immune system, Mice, Inbred C57BL, Cholesterol, Endocrinology, Immunoglobulin G, Immunology, biology.protein, Cytokines, Antibody, Regular Articles
Abstract

Atherosclerotic lesions contain T lymphocytes, which orchestrate adaptive immunity and regulate many innate immune pathways. This study examined the influence of Th1 and Th2 helper cell subsets on atherogenesis in two ApoE(-/-) mouse strains, C57BL/6 and BALB/c, which display opposite T-cell subset polarizations. ApoE(-/-) BL/6 mice showed predominant Th1-like immune responses on polyclonal stimulation of splenic CD4(+) T cells and had IgG2a antibodies to oxidized low-density lipoprotein (a disease-related antigen) whereas ApoE(-/-) BALB/c mice displayed predominant Th2 responses by CD4(+) T cells and an IgG1 isotype response toward oxidized low-density lipoprotein. ApoE(-/-) BL/6 and BALB/c mice consumed a high-cholesterol diet for 10, 16, and 24 weeks with equivalent cholesterolemic responses. The Th1-slanted BL/6 mice developed significantly more atherosclerosis in the aortic root and abdominal aorta at all time points compared with BALB/c mice, supporting a proatherogenic role for Th1 response. Progression of atherosclerosis was associated with increased levels of interleukin (IL)-6 in mouse serum and CD4(+) T-cell culture supernatants and increased levels of the acute-phase protein, serum amyloid A (SAA). Both IL-6 and SAA levels rose significantly in ApoE(-/-) BL/6 mice compared with BALB/c mice. The circulating cytokine milieu (IL-6) and acute phase reactants such as SAA may reflect alterations in the Th1/Th2 balance. The results presented here illustrate how genetically determined modifiers of both immune and inflammatory responses can modulate atherogenesis independently of lipid levels.

Published
2008
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9. Sarcoidosis Mimicking Metastatic Breast Cancer

Author

Ritu R. Gill, Yolanda L. Colson, Sara M. Tolaney, Eric P. Winer, Lawrence N. Shulman, Stephanie Schulte, and Margaret M. Duggan

Subjects
Adult, Oncology, Cancer Research, medicine.medical_specialty, Sarcoidosis, Locally advanced, Breast Neoplasms, Disease, Malignancy, Diagnosis, Differential, Breast Diseases, Breast cancer, Internal medicine, Biopsy, medicine, Humans, medicine.diagnostic_test, business.industry, Middle Aged, medicine.disease, Immunohistochemistry, Dermatology, Metastatic breast cancer, Positron-Emission Tomography, Invasive lobular carcinoma, Female, Tomography, X-Ray Computed, business
Abstract

The clinical and radiographic aspects of sarcoidosis and malignancy might mimic one another, making the distinction between the two difficult in some cases. Although there have been many theories on the link between sarcoidosis and malignancy, the association remains unproven. An unfortunate consequence of the presence of both entities in the same patient is the risk of misdiagnosis and incorrect treatment. We describe 3 patients who presented with locally advanced breast cancer and who were found to have pulmonary findings for metastatic disease that were proven upon biopsy to be consistent with sarcoidosis.

Published
2007
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10. Clinical, pathologic, and outcome study of hyperplastic and sessile serrated polyps in inflammatory bowel disease

Author

Francis A. Farraye, Amitabh Srivastava, Joanna Gibson, Robert D. Odze, Stephanie Schulte, Hema Khurana, Jonathan S. Levine, Taha Qazi, Jeanne Shen, Matthew J. Hamilton, Sandra Cerda, and Robert Burakoff

Subjects
Adenoma, Adult, Male, medicine.medical_specialty, Pathology, Colonic Polyps, Adenocarcinoma, Gastroenterology, Inflammatory bowel disease, Pathology and Forensic Medicine, Lesion, Cohort Studies, Young Adult, Internal medicine, Intestinal Neoplasms, medicine, Humans, Aged, Retrospective Studies, Hyperplasia, business.industry, Middle Aged, medicine.disease, Inflammatory Bowel Diseases, Ulcerative colitis, digestive system diseases, Hyperplastic Polyp, Dysplasia, Female, medicine.symptom, business, Precancerous Conditions, Sessile serrated adenoma
Abstract

There is evidence that some cancers in patients with inflammatory bowel disease (IBD) develop via the serrated pathway of carcinogenesis. This study examined the clinicopathological features and outcome of 115 IBD patients (65 with ulcerative colitis, 50 with Crohn disease), all with at least 1 serrated polyp at endoscopy or colon resection, including the presence of synchronous and metachronous conventional neoplastic lesions (dysplasia or adenocarcinoma), over an average follow-up period of 56.4 months. Conventional neoplasia was categorized as flat dysplasia (low or high grade), sporadic adenoma, adenoma-like dysplasia-associated lesion or mass, or adenocarcinoma. Overall, 97% of patients had at least 1 hyperplastic polyp (HP), 6% had a sessile serrated adenoma/polyp, and none had a traditional serrated adenoma. Eight patients (7%) had a synchronous conventional neoplastic lesion; only 1 had flat dysplasia (1%) and 2 had adenocarcinoma (2%). Thirteen patients developed a metachronous conventional neoplastic lesion, with 8 developing their conventional neoplasm within an area of previous or concurrent colitis; only 1 patient developed flat dysplasia (1%), and none developed adenocarcinoma. A higher proportion of patients with both an HP and a synchronous conventional neoplastic lesion at index developed a metachronous conventional neoplastic lesion, compared with those with an index HP only (25% versus 7%). These results suggest that IBD patients (both ulcerative colitis and Crohn disease patients) with HP have a very low risk of developing a conventional neoplastic lesion (flat dysplasia or adenocarcinoma) that would warrant surgical resection.

Published
2015

11. Evidence for a dualistic model of high-grade serous carcinoma: BRCA mutation status, histology, and tubal intraepithelial carcinoma

Author

Emily E. Meserve, James E. Conner, Christopher P. Crum, Douglas I. Lin, Suchanan Hanamornroongruang, Neil S. Horowitz, Brooke E. Howitt, and Stephanie Schulte

Subjects
Adult, medicine.medical_specialty, animal structures, endocrine system diseases, DNA Mutational Analysis, Kaplan-Meier Estimate, Asymptomatic, Models, Biological, Germline, Pathology and Forensic Medicine, Predictive Value of Tests, Risk Factors, medicine, Biomarkers, Tumor, Fallopian Tube Neoplasms, Humans, Genetic Predisposition to Disease, skin and connective tissue diseases, High-grade serous carcinoma, Aged, Gynecology, Aged, 80 and over, BRCA2 Protein, Ovarian Neoplasms, business.industry, BRCA1 Protein, BRCA mutation, Age Factors, Histology, Middle Aged, female genital diseases and pregnancy complications, Tubal Intraepithelial Carcinoma, Serous fluid, Phenotype, Treatment Outcome, Mutation, Surgery, Female, Anatomy, medicine.symptom, Neoplasm Grading, business, Neoplasms, Cystic, Mucinous, and Serous, Carcinoma in Situ, Boston
Abstract

Most early adnexal carcinomas detected in asymptomatic women with germline BRCA mutations (BRCA) present as serous tubal intraepithelial carcinomas (STIC). However, STICs are found in only ∼40% of symptomatic high-grade serous carcinomas (HGSCs) and less frequently in pseudoendometrioid variants of HGSC. Consecutive cases of untreated HGSC from BRCA and BRCA women with detailed fallopian tube examination (SEE-FIM protocol) were compared. STIC status (+/-) was determined, and tumors were classified morphologically as SET ("SET",50% solid, pseudoendometrioid, or transitional) or classic predominate ("Classic"). SET tumors trended toward a higher frequency in BRCA versus BRCA women (50% vs. 28%, P=0.11), had a significantly younger mean age than those with classic HGSC in BRCA women (mean 56.2 vs. 64.8 y, P=0.04), and displayed a better clinical outcome in both groups combined (P=0.024). STIC was significantly more frequent in tumors from the BRCA cohort (66% vs. 31%, P=0.017) and specifically the BRCA tumors with classic morphology (83%) versus those with SET morphology (22%, P=0.003). Overall, several covariables-histology, BRCA status, age, coexisting STIC, and response to therapy-define 2 categories of HGSC with differences in precursor (STIC) frequency, morphology, and outcome. We introduce a dualistic HGSC model that could shed light on the differences in frequency of STIC between symptomatic and asymptomatic women with HGSC. This model emphasizes the need for further study of HGSC precursors to determine their relevance to the prevention of this lethal malignancy.

Published
2015

12. Nachsprechen von Sätzen bei PPA-L

Author

Walter Huber, Yosef Grodzinsky, Inga Lange, K. Hohlbaum, Katrin Amunts, L. Etcheverry, Stefan Heim, Stephanie Schulte, Martin Südmeyer, Marion Grande, Martina Minnerop, Barbara Wellner, and Katharina Dressel

Subjects
Psychiatry and Mental health, Applied Psychology
Published
2015
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13. Cystatin C Deficiency Promotes Inflammation in Angiotensin II–Induced Abdominal Aortic Aneurisms in Atherosclerotic Mice

Author

Peter Libby, Chongxiu Sun, Jiusong Sun, Stephanie Schulte, Marco Lopez-Ilasaca, Guo-Ping Shi, Galina K. Sukhova, and Lindsey A MacFarlane

Subjects
medicine.medical_specialty, Leukocyte adhesion molecule, Myocytes, Smooth Muscle, Inflammation, macromolecular substances, Pathology and Forensic Medicine, Pathogenesis, Mice, Apolipoproteins E, Internal medicine, medicine, Leukocytes, Leukocyte proliferation, Animals, Humans, Cystatin C, Cell Proliferation, Mice, Knockout, biology, Cell adhesion molecule, Angiotensin II, Anatomy, Atherosclerosis, Mice, Inbred C57BL, Endocrinology, biology.protein, cardiovascular system, medicine.symptom, Elastin, Cell Adhesion Molecules, Regular Articles, Aortic Aneurysm, Abdominal
Abstract

An imbalance between cysteinyl cathepsins and their principal endogenous inhibitor cystatin C (CystC) may favor proteolysis in the pathogenesis of human abdominal aortic aneurysms (AAA), yet a direct role of CystC in AAA remains unproven. This study used CystC and apolipoprotein E (ApoE) compound mutant (CystC(-/-)ApoE(-/-)) mice to examine directly the role of cysteine protease/protease inhibitor imbalance in AAA formation in angiotensin II-induced AAA. CystC-deficiency increased lumenal diameter and lesion size compared with control mice. CystC(-/-) ApoE(-/-) lesions also demonstrated enhanced inflammatory cell accumulation, more severe elastin fragmentation, and fewer smooth muscle cells in the tunica media. Macrophage content, measured as percent positive area (23.2 +/- 1.4% versus 11.2 +/- 1.4%; P = 0.0003) and number of the CD4(+) T cells (ninefold; P = 0.048), increased significantly in CystC(-/-)ApoE(-/-) lesions. CystC deficiency increased cathepsin activity (5.5 fold; P = 0.001) in AAA, yielding greater elastin degradation and proangiogenic laminin-5 gamma2 peptide production, which may account for increased microvascularization in CystC(-/-)ApoE(-/-) compared with ApoE(-/-) lesions. Increased leukocyte adhesion molecule VCAM-1 expression and leukocyte proliferation might also promote inflammation in CystC-deficient AAA. These data indicate that CystC contributes to experimental AAA pathogenesis and that enhanced cysteine protease activity, due to the lack of CystC, favors inflammation in AAA lesions induced in atherosclerotic mice by promoting microvascularization and smooth muscle cell apoptosis as well as leukocytes adhesion and proliferation.

Published
2010

14. Fibroblastic reaction and vascular maturation in human colon cancers

Author

Stephanie Schulte, Leoni A. Kunz-Schughart, Andreas Gaumann, Antje Dietrich, and S Schmid

Subjects
Pathology, medicine.medical_specialty, Stromal cell, Colorectal cancer, Transplantation, Heterologous, H&E stain, Mice, Nude, Biology, Cytokine Receptor Common beta Subunit, Mice, In vivo, medicine, Animals, Humans, Radiology, Nuclear Medicine and imaging, Cells, Cultured, Radiological and Ultrasound Technology, Neovascularization, Pathologic, Fibroblasts, medicine.disease, HCT116 Cells, Immunohistochemistry, Desmoplasia, Transplantation, medicine.anatomical_structure, Colonic Neoplasms, Female, Pericyte, medicine.symptom, Stromal Cells, Pericytes, Neoplasm Transplantation
Abstract

Purpose: The objective of the present study was to provide evidence for the hypothesis of fibroblasts and the desmoplastic reaction, respectively, to impact the formation and maturation of the vascular network in human colon tumours via a retrospective in situ study. An in vivo xenograft model was evaluated to verify its potential for fibroblast-related functional studies. Materials and methods: In situ: Fiftytwo G2/G3 colon tumours were histomorphologically categorised into low (550%), medium (50‐75%) and high (475%) grade desmoplasia based on hematoxylin/eosin and Elastica van Gieson stained paraffin sections. Low and high grade desmoplastic tumours were identified and stained for endothelial and pericyte markers to morphometrically analyse microvessel count (MVC), vascular surface area (VSA) and vascular maturation status. In vivo: One out of three established subcutaneous xenograft model in NMRI (nu/nu) mice was adapted to monitor the impact of primary human fibroblasts on xenograft formation and morphology. Results: Vascular structures in human colon tumours are predominantly located in the fibroblastic stromal regions. Highly desmoplastic tumours, however, have significantly lower MVC and VSA values at the invasion front with signs for augmented vascular maturation as compared with low grade desmoplastic colon cancers. Our in vivo approach verified that only high proportions of co-injected normal fibroblasts accelerate xenograft formation of HCT-116 colon cancer cells. Conclusions: The in situ data clearly support the hypothesis of fibroblasts to contribute to vascular maturation phenomena in colon cancers. The in vivo design of only 500 tumour cells co-injected with normal fibroblast is feasible, results in 100% engraftment and is the basis for further developments.

Published
2009

15. Desmoplasia is accompanied by vascular maturation in colon cancer

Author

Stephanie Schulte, Leoni Kunz-Schughart, Schmid Stephan, Ferdinand Hofstädter, and Andreas Gaumann

Subjects
business.industry, Colorectal cancer, Genetics, Cancer research, medicine, medicine.symptom, business, medicine.disease, Molecular Biology, Biochemistry, Biotechnology, Desmoplasia
Published
2007
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16. Abstract POSTER-CTRL-1208: A dualistic model for the origin of high-grade serous carcinoma: BRCA mutation status, histology and tubal intraepithelial carcinoma

Author

Brooke E. Howitt, Douglas I. Lin, James E. Conner, Judy Garber, Stephanie Schulte, Christopher P. Crum, Emily E. Meserve, and Suchanan Hanamornroongruang

Subjects
Gynecology, Cancer Research, medicine.medical_specialty, education.field_of_study, endocrine system diseases, business.industry, Serous carcinoma, BRCA mutation, Population, Cancer, Serous Tubal Intraepithelial Carcinoma, Histology, medicine.disease, female genital diseases and pregnancy complications, medicine.anatomical_structure, Oncology, Medicine, business, Ovarian cancer, education, Fallopian tube
Abstract

Extra-uterine high-grade serous carcinoma (HGSC) is linked to the fimbria via serous tubal intraepithelial carcinoma or STIC. Women with deleterious BRCA1/2 germ-line mutations (BRCA+) are at high risk for HGSC and ~5% of risk reducing salpingo-oophorectomies harbor a STIC. However, STIC is found in only~40% of the HGSC population and less frequently in endometrioid variants of HGSC (Roh 2009). Consecutively tested women with untreated HGSC, with detailed fallopian tube examination (SEE-FIM protocol), who had germ-line BRCA testing were studied. STIC status was determined by histologic exam, and tumors were classified as predominately SET (> 50% solid, endometrioid-like, or transitional, Soslow 2012) or classic histology. SET features trended towards a higher frequency in BRCA+ vs BRCA- women (50 vs 28%, p = .11). BRCA- subjects with SET morphology were significantly younger than those with classic HGSC (mean 56.2 vs 64.8 years; p=0.04), with a generally better clinical outcome. STIC was significantly more frequent in BRCA- tumors (66 vs 31%, p = 0.017) and more frequent in classic HGSCs in BRCA- (83 vs 22%, p = 0.003) women. Overall, several co-variables – histology, BRCA status, age, coexisting STIC, response to therapy - suggest two categories of HGSC with differences in speed of development, progression, outcome, histology, and possibly, precursor type. We introduce a dualistic HGSC model with a faster evolving tumor type that is not linked to a long-standing STIC. Resolving the nature of this second pathway is germane to both resolving the precursors and expectations from both screening and prevention of HGSC. Citation Format: Brooke E Howitt MD, Suchanan Hanamornroongruang MD, Douglas Lin MD PhD, James E Conner MD PhD, Stephanie Schulte MD, Judy Garber MD, Christopher P Crum MD, Emily E Meserve MD MPH. A dualistic model for the origin of high-grade serous carcinoma: BRCA mutation status, histology and tubal intraepithelial carcinoma [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-CTRL-1208.

Published
2015
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17. A Man with Diarrhea and Back Pain

Author

Derrick J. Todd, Anand Vaidya, Melanie Schorr, Stephanie Schulte, and Alene Conant

Subjects
medicine.medical_specialty, Diarrhea, Abdominal pain, business.industry, Feature (computer vision), medicine, Back pain, Physical therapy, General Medicine, medicine.symptom, business, Surgery
Abstract

This interactive feature presents the case of a 43-year-old man with a 6-week history of constant and diffuse abdominal pain and diarrhea six to seven times daily. Test your diagnostic and therapeutic skills at NEJM.org.

Published
2015
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18. Lactate adversely affects the in vitro formation of endothelial cell tubular structures through the action of TGF-beta1

Author

S Schmid, Stephanie Schulte, Andreas Gaumann, Christoph Eckermann, Leoni A. Kunz-Schughart, Marit Wondrak, Denys N. Wheatley, and Wolfgang Mueller-Klieser

Subjects
Endothelium, Angiogenesis, Cell Survival, Cell, Population, Neovascularization, Physiologic, Biology, Transforming Growth Factor beta1, Cell Movement, Neutralization Tests, medicine, Humans, Lactic Acid, RNA, Messenger, Fibroblast, education, Cell Proliferation, Tumor microenvironment, education.field_of_study, Cell growth, Endothelial Cells, Cell Biology, Fibroblasts, Actins, Coculture Techniques, Cell biology, Endothelial stem cell, medicine.anatomical_structure, Gene Expression Regulation, Immunology
Abstract

When lactate accumulation in a tumor microenvironment reaches an average concentration of 10-20 mM, it tends to reflect a high degree of malignancy. However, the hypothesis that tumor-derived lactate has a number of partially adverse biological effects on malignant and tumor-associated host cells requires further evidence. The present study attempted to evaluate the impact of lactate on the process of angiogenesis, in particular on the formation of tubular structures. The endothelial cell (EC) network in desmoplastic breast tumors is primarily located in areas of reactive fibroblastic stroma. We employed a fibroblast-endothelial cell co-culture model as in vitro angiogenesis system normally producing florid in vitro tubule formation to analyze this situation. In contrast to previous studies, we found that lactate significantly reduces EC network formation in a dose-dependent manner as quantified by semi-automated morphometric analyses following immunohistochemical staining. The decrease in CD31-positive tubular structures and the number of intersections was independent of VEGF supplementation and became more pronounced in the presence of protons. The number of cells, primarily of the fibroblast population, was reduced but cell loss could not be attributed to a decrease in proliferative activity or pronounced apoptotic cell death. Treatment with 10 mM lactate was accompanied by enhanced mRNA expression and release of TGF-beta1, which also shows anti-angiogenic activity in the model. Both TGF-beta1 and lactate induced myofibroblastic differentiation adjacent to the EC tubular structures. The lactate response on the EC network was diminished by TGF-beta1 neutralization, indicating a causal relationship between lactate and TGF-beta1 in the finely tuned processes of vessel formation and maturation which may also occur in vivo within tumor tissue.

Published
2006

19. Human leukocyte antigen class II immune response genes, female gender, and cigarette smoking as risk and modulating factors in abdominal aortic aneurysms

Author

Henry D. Tazelaar, W. Michael O'Fallon, Stephanie Schulte, Virginia M. Miller, Cornelia M. Weyand, John W. Hallett, and Todd E. Rasmussen

Subjects
Male, medicine.medical_specialty, Pathology, Genes, MHC Class II, Human leukocyte antigen, 030204 cardiovascular system & hematology, Gastroenterology, Severity of Illness Index, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Aneurysm, Sex Factors, HLA Antigens, Risk Factors, Internal medicine, medicine.artery, medicine, Humans, 030212 general & internal medicine, Risk factor, Aged, Aged, 80 and over, Vascular disease, business.industry, Abdominal aorta, Smoking, Odds ratio, Middle Aged, medicine.disease, Abdominal aortic aneurysm, 3. Good health, cardiovascular system, Surgery, Female, business, Cardiology and Cardiovascular Medicine, Aortic Aneurysm, Abdominal
Abstract

Objective: Aortic inflammation and the genes that regulate the immune response play an important role in abdominal aortic aneurysm pathogenesis. However, the modulating effects of such genetic and other environmental factors on the severity on aneurysm inflammation is not known. The objective of this study was to determine the influence of the human leukocyte antigen (HLA) class II genes, gender, and environmental factors on degree of abdominal aortic aneurysm tissue inflammation. Methods: Aneurysm specimens were obtained at the time of operation from 96 consecutive patients who underwent abdominal aortic aneurysm repair and were graded for degree of histologic inflammation. Multivariate analysis was used to determine the association of genetic and environmental factors with degree of inflammation and to determine the HLA-associated disease risk for aneurysm. Results: Active cigarette smoking and female gender were independently associated with high-grade tissue inflammation identified histologically (odds ratio [OR], confidence interval [CI]: 5.6, 1.6 to 19.3; and 6.0, 1.4 to 26.2, respectively), and a specific HLA allele (DR B1 * 01) was inversely associated with inflammation (OR, CI: 0.2, 0.04 to 0.7). Overall, the HLA-DR B1 * 02 and B1 * 04 alleles were significantly associated with disease risk, more than doubling risk for abdominal aortic aneurysm (OR, CI: 2.5, 1.4 to 4.3; and 2.1, 1.2 to 3.7, respectively). Conclusion: Active cigarette smoking and female gender are significant disease-modulating factors associated with increased abdominal aortic aneurysm inflammation. In addition, the HLA class II immune response genes possess both disease modulating and disease risk properties, which may be useful in early aneurysm detection and surveillance. (J Vasc Surg 2002;35:988-93.)

Published
2002

20. T-cell-mediated lysis of endothelial cells in acute coronary syndromes

Author

Stephanie Schulte, Stephen L. Kopecky, Kenneth J. Warrington, Cornelia M. Weyand, Takako Nakajima, Jörg J. Goronzy, and Robert L. Frye

Subjects
CD4-Positive T-Lymphocytes, Pore Forming Cytotoxic Proteins, T cell, Autoimmunity, Coronary Artery Disease, Major histocompatibility complex, Interleukin 21, Antigen, CD28 Antigens, T-Lymphocyte Subsets, Physiology (medical), Cytotoxic T cell, Medicine, Humans, Lectins, C-Type, IL-2 receptor, Angina, Unstable, Cells, Cultured, Aged, Membrane Glycoproteins, biology, business.industry, Perforin, T lymphocyte, Middle Aged, Cytotoxicity Tests, Immunologic, Flow Cytometry, Molecular biology, Clone Cells, medicine.anatomical_structure, C-Reactive Protein, Strontium, Immunology, Acute Disease, Antigens, Surface, Interleukin 12, biology.protein, Female, Endothelium, Vascular, Cardiology and Cardiovascular Medicine, business, NK Cell Lectin-Like Receptor Subfamily B, T-Lymphocytes, Cytotoxic
Abstract

Background — CD4 T lymphocytes accumulate in unstable plaque. The direct and indirect involvement of these T cells in tissue injury and plaque instability is not understood. Methods and Results — Gene profiling identified perforin, CD161, and members of the killer-cell immunoglobulin-like receptors as being differentially expressed in CD4 + CD28 null T cells, a T-cell subset that preferentially infiltrates unstable plaque. Frequencies of CD161 + and perforin-expressing CD4 T cells in peripheral blood were significantly increased in patients with unstable angina (UA). CD161 appeared on CD4 + CD28 null T cells after stimulation, suggesting spontaneous activation of circulating CD4 T cells in UA. Perforin-expressing CD4 + T-cell clones from patients with UA exhibited cytotoxic activity against human umbilical vein endothelial cells (HUVECs) in redirected cytotoxicity assays after T-cell receptor triggering and also after stimulation of major histocompatibility complex class I–recognizing killer-cell immunoglobulin-like receptors. HUVEC cytolysis was dependent on granule exocytosis, as demonstrated by the paralyzing effect of pretreating CD4 + CD28 null T cells with strontium. Incubation of HUVECs with C-reactive protein (CRP) increased HUVEC lysis in a dose-dependent fashion. Conclusions — In patients with UA, CD4 T cells undergo a change in functional profile and acquire cytotoxic capability. Cytotoxic CD4 T cells effectively kill endothelial cells; CRP sensitizes endothelial cells to the cytotoxic process. We propose that T-cell–mediated endothelial cell injury is a novel pathway of tissue damage that contributes to plaque destabilization. The sensitizing effect of CRP suggests synergy between dysregulated T-cell function and acute phase proteins in acute coronary syndromes.

Published
2002

21. Epicutaneous sensitization results in IgE-dependent intestinal mast cell expansion and food-induced anaphylaxis

Author

Lisa M. Bartnikas, Sabine Leisten, Michiko K. Oyoshi, Jason L. Hornick, Oliver T. Burton, Michael F. Gurish, Jacqueline Beaupré, Raif S. Geha, K. Frank Austen, Stephanie Schulte, Hans C. Oettgen, Erin Janssen, and Christopher N. Lewis

Subjects
Cholera Toxin, Ovalbumin, Immunology, Administration, Cutaneous, Immunoglobulin E, Antibodies, Article, Immunoglobulin G, Body Temperature, Mice, Food allergy, medicine, Animals, Immunology and Allergy, Mast Cells, Antigens, Anaphylaxis, Chemokine CCL2, Sensitization, Skin, Mice, Inbred BALB C, biology, business.industry, Allergens, medicine.disease, Mast cell, Jejunum, medicine.anatomical_structure, biology.protein, Interleukin-4, Antibody, business, Food Hypersensitivity
Abstract

Background Sensitization to food antigen can occur through cutaneous exposure. Objective We sought to test the hypothesis that epicutaneous sensitization with food antigen predisposes to IgE-mediated anaphylaxis on oral allergen challenge. Methods BALB/c mice were epicutaneously sensitized by repeated application of ovalbumin (OVA) to tape-stripped skin over 7 weeks or orally immunized with OVA and cholera toxin (CT) weekly for 8 weeks and then orally challenged with OVA. Body temperature was monitored, and serum mouse mast cell protease 1 levels were determined after challenge. Tissue mast cell (MC) counts were examined by using chloroacetate esterase staining. Levels of serum OVA-specific IgE and IgG 1 antibodies and cytokines in supernatants of OVA-stimulated splenocytes were measured by means of ELISA. Serum IL-4 levels were measured by using an in vivo cytokine capture assay. Results Epicutaneously sensitized mice exhibited expansion of connective tissue MCs in the jejunum, increased serum IL-4 levels, and systemic anaphylaxis after oral challenge, as evidenced by decreased body temperature and increased serum mouse mast cell protease 1 levels. Intestinal MC expansion and anaphylaxis were IgE dependent because they did not occur in epicutaneously sensitized IgE −/− mice. Mice orally immunized with OVA plus CT did not have increased serum IL-4 levels, expanded intestinal MCs, or anaphylaxis after oral challenge, despite OVA-specific IgE levels and splenocyte cytokine production in response to OVA stimulation, which were comparable with those of epicutaneously sensitized mice. Conclusion Epicutaneously sensitized mice, but not mice orally immunized with antigen plus CT, have expansion of intestinal MCs and IgE-mediated anaphylaxis after single oral antigen challenge. IgE is necessary but not sufficient for food anaphylaxis, and MC expansion in the gut can play an important role in the development of anaphylaxis.

Published
2013
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23. Endovascular Treatment of Profunda Femoris Artery Obstructive Disease: Nonsense or Useful Tool in Selected Cases?

Author

M. Camci, Giovanni Federico Torsello, Konstantinos P. Donas, Stephanie Schulte, R. Schlabach, Georgios A. Pitoulias, and Arne Schwindt

Subjects
Male, Time Factors, medicine.medical_treatment, Constriction, Pathologic, Kaplan-Meier Estimate, Femoral artery, Balloon, Severity of Illness Index, Restenosis, Ischemia, Germany, Occlusion, Aged, 80 and over, Medicine(all), Ultrasonography, Doppler, Duplex, Middle Aged, Limb Salvage, PTA, Critical limb ischaemia, Femoral Artery, Treatment Outcome, medicine.anatomical_structure, Profundoplasty, Female, Stents, Radiology, Cardiology and Cardiovascular Medicine, Vascular Surgical Procedures, medicine.medical_specialty, Critical Illness, Arterial Occlusive Diseases, Duplex scanning, Angioplasty, medicine.artery, medicine, Humans, Endovascular treatment, Profunda femoris artery occlusive disease, Vascular Patency, Aged, Retrospective Studies, Groin, business.industry, Patient Selection, Vascular surgery, medicine.disease, Surgery, Radiography, business, Angioplasty, Balloon
Abstract

Background To evaluate the therapeutic value of endovascular techniques for the treatment of profunda femoris artery obstructive disease (PFAOD) in critical limb ischaemia (CLI) patients, with technically demanding open profunda repair. Design Retrospective study of prospectively collected data of 15 consecutive CLI patients with technically demanding surgical treatment of PFAOD, that were treated by endovascular means in two European Centers of Vascular Surgery. Materials All patients had critical limb ischaemia with a history of at least two previous vascular reconstructions in the ipsilateral groin and severe co-morbid conditions. All patients had good common femoral artery flow, long occlusion of the superficial femoral and popliteal arteries and impairment of crural arteries. Methods Twelve patients underwent balloon angioplasty alone and, in the other three cases, an additional stent placement was necessary, due to flow-limiting dissection. The follow-up (mean 29.2 ± 10 months) included a surveillance protocol with the best medical treatment and duplex scanning at 1, 3, 6, 12 months and yearly thereafter. Results The endovascular approach was technically successful in all cases and the procedure-related morbidity and mortality rates were 0% for the entire follow-up period. The 3-year primary and secondary patency rates of the treated segment were 80% and 86.7%, respectively. The limb salvage rate was 93.3%. Conclusions The outcome of our series underscores the therapeutic value of balloon angioplasty in cases of severe PFAOD, as bailout treatment in critical limb ischaemia patients with technically demanding open profunda repair. This procedure can be repeated easily if significant restenosis occurs and provides a useful tool in selected cases.

Published
2010
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