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Emons, Georg ; Auslander, Noam ; Jo, Peter ; Kitz, Julia ; Azizian, Azadeh ; Hu, Yue ; Hess, Clemens F. ; Rödel, Claus ; Sax, Ulrich ; Salinas-Riester, Gabriela ; Ströbel, Philipp ; Kramer, Frank ; Beissbarth, Tim ; Ghadimi, Michael ; Ruppin, Eytan ; Ried, Thomas ; Gaedcke, Jochen Werner Christian ; Grade, Marian
Purpose: Preoperative (neoadjuvant) chemoradiotherapy (CRT) and total mesorectal excision is the standard treatment for rectal cancer patients (UICC stage II/III). Up to one-third of patients treated with CRT achieve a pathological complete response (pCR). These patients could be spared from surgery and its associated morbidity and mortality, and assigned to a “watch and wait” strategy. However, reliably identifying pCR based on clinical or imaging parameters remains challenging.
Experimental design: We generated gene-expression profiles of 175 patients with locally advanced rectal cancer enrolled in the CAO/ARO/AIO-94 and -04 trials. One hundred and sixty-one samples were used for building, training and validating a predictor of pCR using a machine learning algorithm. The performance of the classifier was validated in three independent cohorts, comprising 76 patients from (i) the CAO/ARO/AIO-94 and -04 trials (n = 14), (ii) a publicly available dataset (n = 38) and (iii) in 24 prospectively collected samples from the TransValid A trial.
Results: A 21-transcript signature yielded the best classification of pCR in 161 patients (Sensitivity: 0.31; AUC: 0.81), when not allowing misclassification of non-complete-responders (False-positive rate = 0). The classifier remained robust when applied to three independent datasets (n = 76).
Conclusion: The classifier can identify >1/3 of rectal cancer patients with a pCR while never classifying patients with an incomplete response as having pCR. Importantly, we could validate this finding in three independent datasets, including a prospectively collected cohort. Therefore, this classifier could help select rectal cancer patients for a “watch and wait” strategy.
Translational relevance: Forgoing surgery with its associated side effects could be an option for rectal cancer patients if the prediction of a pathological complete response (pCR) after preoperative chemoradiotherapy would be possible. Based on gene-expression profiles of 161 patients a classifier was developed and validated in three independent datasets (n = 76), identifying over 1/3 of patients with pCR, while never misclassifying a non-complete-responder. Therefore, the classifier can identify patients suited for “watch and wait”.
Ziel der vorliegenden Arbeit war es, die Mechanismen aufzuklären, die im Rahmen inflammatorischer Erkrankungen zur Expression sogenannter Akute Phase Proteine führen. Der Fokus lag hierbei auf der Untersuchung von Signaltransduktionkaskaden, die aktiviert durch proinflammatorische Zytokine in der Leber die Bildung proatherogener Plasmaproteine wie C-reaktives Protein zur Folge haben. Zu diesem Zweck sollten verschiedene in vitro Zellmodelle etabliert und evaluiert werden. Neben Genexpressionsanalysen in zytokin-stimulierten primären humanen Hepatozyten, sowie in den Hepatoma-Zellinien HepG2 und Hep3B sollte die Manipulation der CRP-Expression durch gezielten Gentransfer und die Anwendung der siRNA-Technologie im Mittelpunkt dieser Arbeit stehen. Zu diesem Zweck sollten Transkriptionsfaktoren der NFKB-Familie, sowie der Familie der „Signal transducer and activator of transcription“ (STAT) und der CCAAT/Enhancer-bindenden Proteine (C/EBP) überexprimiert werden, bzw. deren Expression durch die Transfektion mit entsprechenden siRNA-Oligonukleotide gehemmt werden. Ein weiteres wichtiges Ziel war es, ein zelluläres Modellsystem zu generieren und zu charakt-erisieren, das zur Identifizierung von Substanzen geeignet ist, die die CRP-Expression modu-lieren oder inhibieren.
Gabler, Matthias ; Kramer, Jan ; Schmidt, Jurema ; Pollinger, Julius Carl ; Weber, Julia ; Kaiser, Astrid ; Löhr, Frank ; Proschak, Ewgenij ; Schubert-Zsilavecz, Manfred ; Merk, Daniel
The bile acid activated transcription factor farnesoid X receptor (FXR) regulates numerous metabolic processes and is a rising target for the treatment of hepatic and metabolic disorders. FXR agonists have revealed efficacy in treating non-alcoholic steatohepatitis (NASH), diabetes and dyslipidemia. Here we characterize imatinib as first-in-class allosteric FXR modulator and report the development of an optimized descendant that markedly promotes agonist induced FXR activation in a reporter gene assay and FXR target gene expression in HepG2 cells. Differential effects of imatinib on agonist-induced bile salt export protein and small heterodimer partner expression suggest that allosteric FXR modulation could open a new avenue to gene-selective FXR modulators.
Théry, Clotilde ; Witwer, Kenneth W. ; Aikawa, Elena ; Alcaraz, Maria Jose ; Anderson, Johnathon D. ; Andriantsitohaina, Ramaroson ; Antoniou, Anna ; Arab, Tanina ; Archer, Fabienne ; Atkin-Smith, Georgia K. ; Ayre, D. Craig ; Bach, Jean-Marie ; Bachurski, Daniel ; Baharvand, Hossein ; Balaj, Leonora ; Baldacchino, Shawn ; Bauer, Natalie N. ; Baxter, Amy A. ; Bebawy, Mary ; Beckham, Carla ; Zavec, Apolonija Bedina ; Benmoussa, Abderrahim ; Berardi, Anna C. ; Bergese, Paolo ; Bielska, Ewa ; Blenkiron, Cherie ; Bobis-Wozowicz, Sylwia ; Boilard, Eric ; Boireau, Wilfrid ; Bongiovanni, Antonella ; Borràs, Francesc E. ; Bosch, Steffi ; Boulanger, Chantal M. ; Breakefield, Xandra ; Breglio, Andrew M. ; Brennan, Meadhbh Aín ; Brigstock, David R. ; Brisson, Alain ; Broekman, Marike L. D. ; Bromberg, Jacqueline F. ; Bryl-Gorecka, Paulina ; Buch, Shilpa ; Buck, Amy H. ; Burger, Dylan ; Busatto, Sara ; Buschmann, Dominik ; Bussolati, Benedetta ; Buzás, Edit I. ; Byrd, James Bryan ; Camussi, Giovanni ; Carter, David R. F. ; Caruso, Sarah ; Chamley, Lawrence W. ; Chang, Yu-Ting ; Chen, Chihchen ; Chen, Shuai ; Cheng, Lesley ; Chin, Andrew R. ; Clayton, Aled ; Clerici, Stefano P. ; Cocks, Alex ; Cocucci, Emanuele ; Coffey, Robert J. ; Cordeiro-da-Silva, Anabela ; Couch, Yvonne ; Coumans, Frank A. W. ; Coyle, Beth ; Crescitelli, Rossella ; Criado, Miria Ferreira ; D’Souza-Schorey, Crislyn ; Das, Saumya ; Chaudhuri, Amrita Datta ; de-Candia, Paola ; De Santana, Eliezer F. ; De Wever, Olivier ; del Portillo, Hernando A. ; Demaret, Tanguy ; Deville, Sarah ; Devitt, Andrew ; Dhondt, Bert ; Di Vizio, Dolores ; Dieterich, Lothar C. ; Dolo, Vincenza ; Dominguez Rubio, Ana Paula ; Dominici, Massimo ; Dourado, Mauricio R. ; Driedonks, Tom A. P. ; Duarte, Filipe V. ; Duncan, Heather M. ; Eichenberger, Ramon Marc ; Ekström, Karin ; El Andaloussi, Samir ; Elie-Caille, Celine ; Erdbrügger, Uta ; Falcón-Pérez, Juan M. ; Fatima, Farah ; Fish, Jason E. ; Flores-Bellver, Miguel ; Försönits, András ; Frelet-Barrand, Annie ; Fricke, Fabia ; Fuhrmann, Gregor ; Gabrielsson, Susanne ; Gámez-Valero, Ana ; Gardiner, Chris ; Gärtner, Kathrin ; Gaudin, Raphael ; Gho, Yong Song ; Giebel, Bernd ; Gilbert, Caroline ; Gimona, Mario ; Giusti, Ilaria ; Goberdhan, Deborah C. I. ; Görgens, André ; Gorski, Sharon M. ; Greening, David W. ; Groß, Julia Christina ; Gualerzi, Alice ; Gupta, Gopal N. ; Gustafson, Dakota ; Handberg, Aase ; Haraszti, Réka Ágnes ; Harrison, Paul ; Hegyesi, Hargita ; Hendrix, An ; Hill, Andrew F. ; Hochberg, Fred H. ; Hoffmann, Karl F. ; Holder, Beth ; Holthofer, Harry ; Hosseinkhani, Baharak ; Hu, Guoku ; Huang, Yiyao ; Huber, Veronica ; Hunt, Stuart ; Ibrahim, Ahmed Gamal-Eldin ; Ikezu, Tsuneya ; Inal, Jameel M. ; Isin, Mustafa ; Ivanova, Alena ; Jackson, Hannah K. ; Jacobsen, Soren ; Jay, Steven M. ; Jayachandran, Muthuvel ; Jenster, Guido ; Jiang, Lanzhou ; Johnson, Suzanne M. ; Jones, Jennifer C. ; Jong, Ambrose ; Jovanovic-Talisman, Tijana ; Jung, Stephanie ; Kalluri, Raghu ; Kano, Shin-ichi ; Kaur, Sukhbir ; Kawamura, Yumi ; Keller, Evan T. ; Khamari, Delaram ; Khomyakova, Elena ; Khvorova, Anastasia ; Kierulf, Peter ; Kim, Kwang Pyo ; Kislinger, Thomas ; Klingeborn, Mikael ; Klinke, David J. ; Kornek, Miroslaw ; Kosanović, Maja M. ; Kovács, Árpád Ferenc ; Krämer-Albers, Eva-Maria ; Krasemann, Susanne ; Krause, Mirja ; Kurochkin, Igor V. ; Kusuma, Gina D. ; Kuypers, Sören ; Laitinen, Saara ; Langevin, Scott M. ; Languino, Lucia R. ; Lannigan, Joanne ; Lässer, Cecilia ; Laurent, Louise C. ; Lavieu, Gregory ; Lázaro-Ibáñez, Elisa ; Le Lay, Soazig ; Lee, Myung-Shin ; Lee, Yi Xin Fiona ; Lemos, Debora S. ; Lenassi, Metka ; Leszczynska, Aleksandra ; Li, Isaac T. S. ; Liao, Ke ; Libregts, Sten F. ; Ligeti, Erzsebet ; Lim, Rebecca ; Lim, Sai Kiang ; Linē, Aija ; Linnemannstöns, Karen ; Llorente, Alicia ; Lombard, Catherine Ann ; Lorenowicz, Magdalena J. ; Lörincz, Ákos M. ; Lötvall, Jan ; Lovett, Jason ; Lowry, Michelle C. ; Loyer, Xavier ; Lu, Quan ; Lukomska, Barbara ; Lunavat, Taral Rameshchand ; Maas, Sybren L. N. ; Malhi, Harmeet ; Marcilla, Antonio ; Mariani, Jacopo ; Mariscal, Javier ; Martens-Uzunova, Elena S. ; Martin-Jaular, Lorena ; Martinez, M. Carmen ; Martins, Vilma Regina ; Mathieu, Mathilde ; Mathivanan, Suresh ; Maugeri, Marco ; McGinnis, Lynda K. ; McVey, Mark J. ; Meckes, David G. ; Meehan, Katie ; Mertens, Inge ; Minciacchi, Valentina R. ; Möller, Andreas ; Møller Jørgensen, Malene ; Morales-Kastresana, Aizea ; Morhayim, Jess ; Mullier, François ; Muraca, Maurizio ; Musante, Luca ; Mussack, Veronika ; Muth, Dillon C. ; Myburgh, Kathryn H. ; Najrana, Tanbir ; Nawaz, Muhammad ; Nazarenko, Irina ; Nejsum, Peter ; Neri, Christian ; Neri, Tommaso ; Nieuwland, Rienk ; Nimrichter, Leonardo ; Nolan, John P. ; Nolte-’t Hoen, Esther N. M. ; Hooten, Nicole Noren ; O’Driscoll, Lorraine ; O’Grady, Tina ; O’Loghlen, Ana ; Ochiya, Takahiro ; Olivier, Martin ; Ortiz, Alberto ; Ortiz, Luis A. ; Osteikoetxea, Xabier ; Østergaard, Ole ; Ostrowski, Matias ; Park, Jaesung ; Pegtel, Dirk Michiel ; Peinado, Hector ; Perut, Francesca ; Pfaffl, Michael ; Phinney, Donald G. ; Pieters, Bartijn C. H. ; Pink, Ryan Charles ; Pisetsky, David S. ; Pogge von Strandmann, Elke ; Polakovicova, Iva ; Poon, Ivan K. H. ; Powell, Bonita H. ; Prada, Ilaria ; Pulliam, Lynn ; Quesenberry, Peter ; Radeghieri, Annalisa ; Raffai, Robert L. ; Raimondo, Stefania ; Rak, Janusz ; Ramirez, Marcel I. ; Raposo, Graça ; Rayyan, Morsi S. ; Regev-Rudzki, Neta ; Ricklefs, Franz Lennard ; Robbins, Paul D. ; Roberts, David D. ; Rodrigues, Silvia C. ; Rohde, Eva ; Rome, Sophie ; Rouschop, Kasper M. ; Rughetti, Aurelia ; Russell, Ashley E. ; Saá, Paula ; Sahoo, Susmita ; Salas-Huenuleo, Edison ; Sánchez, Catherine ; Saugstad, Julie A. ; Saul, Meike J. ; Schiffelers, Raymond M. ; Schneider, Raphael ; Schøyen, Tine Hiorth ; Scott, Aaron ; Shahaj, Eriomina ; Sharma, Shivani ; Shatnyeva, Olga ; Shekari, Faezeh ; Shelke, Ganesh Vilas ; Shetty, Ashok K. ; Shiba, Kiyotaka ; Siljander, Pia R.-M. ; Silva, Andreia M. ; Skowronek, Agata ; Snyder, Orman L. ; Soares, Rodrigo Pedro ; Sódar, Barbara W. ; Soekmadji, Carolina ; Sotillo, Javier ; Stahl, Philip D. ; Stoorvogel, Willem ; Stott, Shannon L. ; Strasser, Erwin F. ; Swift, Simon ; Tahara, Hidetoshi ; Tewari, Muneesh ; Timms, Kate ; Tiwari, Swasti ; Tixeira, Rochelle ; Tkach, Mercedes ; Toh, Wei Seong ; Tomasini, Richard ; Torrecilhas, Ana Claudia ; Tosar, Juan Pablo ; Toxavidis, Vasilis ; Urbanelli, Lorena ; Vader, Pieter ; Balkom, Bastiaan Wilhelmus Maria van ; Grein, Susanne G. van der ; Van Deun, Jan ; Herwijnen, Martijn J. C. van ; Van Keuren-Jensen, Kendall R. ; Niel, Guillaume van ; Royen, Martin E. van ; Wijnen, Andre J. van ; Vasconcelos, M. Helena ; Vechetti, Ivan J. ; Veit, Tiago D. ; Vella, Laura J. ; Velot, Émilie ; Verweij, Frederik ; Vestad, Beate ; Viñas, Jose Luis ; Visnovitz, Tamás ; Vukman, Krisztina V. ; Wahlgren, Jessica ; Watson, Dionysios C. ; Wauben, Marca H. M. ; Weaver, Alissa ; Webber, Jason P. ; Weber, Viktoria ; Wehman, Ann M. ; Weiss, Daniel J. ; Welsh, Joshua A. ; Wendt, Sebastian ; Wheelock, Åsa M. ; Wiener, Zoltán ; Witte, Leonie ; Wolfram, Joy ; Xagorari, Angeliki ; Xander, Patricia ; Xu, Jing ; Yan, Xiaomei ; Yáñez-Mó, María ; Yin, Hang ; Yuana, Yuana ; Zappulli, Valentina ; Zarubova, Jana ; Žėkas, Vytautas ; Zhang, Jian-ye ; Zhao, Zezhou ; Zheng, Lei ; Zheutlin, Alexander R. ; Zickler, Antje Maria ; Zimmermann, Pascale ; Zivkovic, Angela M. ; Zocco, Davide ; Zuba-Surma, Ewa K.
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
Adams, John ; Aggarwal, Madan Mohan ; Ahammed, Zubayer ; Amonett, John ; Anderson, Bryon D. ; Arkhipkin, Dmitry A. ; Averichev, Georgy S. ; Badyal, S. K. ; Bai, Yu ; Balewski, Jan ; Barannikova, Olga ; Barnby, Lee Stuart ; Baudot, Jérome ; Bekele, Selemon ; Belaga, Victoria Vladimirovna ; Bellwied, Rene ; Berger, Jens ; Bezverkhny, B. I. ; Bharadwa, S. ; Bhasin, Anju ; Bhati, Ashok Kumar ; Bhatia, V. S. ; Bichsel, Hans ; Billmeier, Anja ; Bland, Leslie C. ; Blyth, Charles O. ; Bonner, Billy E. ; Botje, Michiel ; Boucham, Abdelkrim ; Brandin, Andrei V. ; Bravar, Alessandro ; Bystersky, M. ; Cadman, R. V. ; Cai, X. Z. ; Caines, Helen Louise ; Calderón de la Barca Sánchez, Manuel ; Castillo Castellanos, Javier Ernesto ; Cebra, Daniel A. ; Chajecki, Zbigniew ; Chaloupka, Petr ; Chattopadhyay, S. ; Chen, H. F. ; Chen, Y. ; Cheng, J. ; Cherney, Michael Gerard ; Chikanian, Alexei ; Christie, William ; Coffin, J. P. ; Cormier, Thomas Michael ; Cramer, John G. ; Crawford, Henry J. ; Das, Debasish ; Das, S. ; Moura, M. M. de ; Derevschikov, Anatoly A. ; Didenko, Lidia ; Dietel, Thomas ; Dogra, Sunil Manohar ; Dong, W. J. ; Dong, X. ; Draper, James E. ; Du, F. ; Dubey, Anand Kumar ; Dunin, V. B. ; Dunlop, James C. ; Dutta Mazumdar, M. R. ; Eckardt, Volker ; Edwards, W. R. ; Efimov, L. G. ; Emelianov, V. ; Engelage, Jon M. ; Eppley, Geary Wareham ; Erazmus, Barbara Ewa ; Estienne, Magali Danielle ; Fachini, Patricia ; Faivre, Julien ; Fatemi, Renee H. ; Fedorišin, Jan ; Filimonov, Kirill ; Filip, Peter ; Finch, Evan ; Fine, Valeri ; Fisyak, Yuri V. ; Fomenko, K. ; Grebenyuk, Oleksandr ; Grosnick, David P. ; Guertin, Steven M. ; Guo, Y. ; Gupta, Anik ; Gutierrez, Thomas Dominic ; Hallman, Timothy J. ; Hamed, Ahmed M. ; Hardtke, David H. ; Harris, John W. ; Heinz, M. ; Henry, Thomas W. ; Hepplemann, S. ; Hippolyte, Boris ; Hirsch, Andrew S. ; Hjort, Eric ; Hoffmann, G. W. ; Huang, H. Z. ; Huang, S. L. ; Hughes, Emlyn Willard ; Humanic, Thomas J. ; Igo, George J. ; Ishihara, A. ; Jacobs, Peter Martin ; Jacobs, W.W. ; Janik, Michał ; Jiang, H. ; Jones, Peter Graham ; Judd, Eleanor G. ; Kabana, Sonia ; Kang, K. ; Kaplan, Morton ; Keane, Declan ; Khodyrev, V. Yu. ; Kiryluk, Joanna ; Kisiel, Adam Ryszard ; Kislov, E. M. ; Klay, Jennifer Lynn ; Klein, Spencer Robert ; Klyachko, A. ; Koetke, Donald D. ; Kollegger, Thorsten ; Kopytine, M. ; Kotchenda, L. ; Kramer, M. ; Kravtsov, Peter ; Kravtsov, Vladimir I. ; Krueger, Keith William ; Kuhn, Christian Claude ; Kulikov, Anatoly I. ; Kumar, Ajay ; Kutuev, R.Kh. ; Kuznetsov, A.A. ; Lamont, Matthew A. C. ; Landgraf, Jeffery M. ; Lange, Jens Sören ; Laue, Frank ; Lauret, Jerome ; Lebedev, Alexei ; Lednicky, Richard ; Lehocka, S. ; LeVine, Micheal J. ; Li, C. ; Li, Q. ; Li, Y. ; Lin, G. ; Lindenbaum, S. J. ; Lisa, Michael A. ; Liu, F. ; Liu, L. ; Liu, Q.J. ; Liu, Z. ; Ljubicic, Tonko A. ; Llope, William Joseph ; Long, H. ; Longacre, Ronald S. ; López Noriega, M. ; Love, William A. ; Lu, Y. ; Ludlam, Thomas ; Lynn, David ; Ma, G. L. ; Ma, Jing-guo ; Ma, Y. G. ; Magestro, Daniel ; Mahajan, Sanjay ; Mahapatra, D. P. ; Majka, Richard Daniel ; Mangotra, Lalit K. ; Manweiler, Robert W. ; Margetis, Spyridon ; Markert, Christina ; Martin, L. ; Marx, Jay N. ; Matis, Howard S. ; Matulenko, Yuri A. ; McClain, C. J. ; McShane, T. S. ; Meissner, F. ; Melnick, Yu. ; Meščanin, Aleksei P. ; Miller, M. L. ; Minaev, Nikolai G. ; Mironov, Camelia ; Mischke, André ; Mishra, D. K. ; Mitchell, J. ; Mohanty, Bedangadas ; Molnar, Levente ; Moore, C. F. ; Morozov, D. A. ; Munhoz, Marcelo Gameiro ; Nandi, Basanta Kumar ; Nayak, S. K. ; Nayak, Tapan Kumar ; Nelson, John M. ; Netrakanti, Pawan Kumar ; Nikitin, Vladimir A. ; Nogach, Larisa V. ; Nurušev, Sandibek B. ; Odyniec, Grazyna Janina ; Ogawa, Akio ; Okorokov, Vitaly A. ; Oldenburg, Markus D. ; Olson, Douglas L. ; Pal, Susanta Kumar ; Panebratsev, Yuri ; Panitkin, Sergei Yurievich ; Pavlinov, A. I. ; Pawlak, Tomasz Jan ; Peitzmann, Thomas ; Pluta, Jan Marian ; Porile, Norbert T. ; Porter, Jeffrey Brent ; Poskanzer, Arthur M. ; Potekhin, Maxim ; Potrebenikova, E. ; Potukuchi, B. V. K. S. ; Prindle, Duncan J. ; Pruneau, Claude A. ; Putschke, Jörn H. ; Rakness, Gregory L. ; Raniwala, Rashmi ; Raniwala, Sudhir ; Ravel, Olivier ; Ray, Robert L. ; Razin, Sergej V. ; Reichhold, Dennis Michael ; Reid, Jeffrey G. ; Renault, G. ; Retiere, Fabrice ; Ridiger, Alexey ; Ritter, Hans Georg ; Roberts, Jabus B. ; Rogačevskij, Oleg V. ; Romero, Juan L. ; Rose, A. ; Roy, Christelle Sophie ; Ruan, Lijuan ; Sahoo, Raghunath ; Sakrejda, Iwona ; Salur, Sevil ; Sandweiss, Jack H. ; Savin, Igor A. ; Sazhin, P. S. ; Schambach, Joachim ; Scharenberg, Rolf Paul ; Schmitz, Norbert ; Schweda, Kai ; Seger, Janet Elizabeth ; Seyboth, Peter ; Shahaliev, Ehtiram ; Shao, M. ; Shao, W. ; Sharma, M. ; Shen, W. Q. ; Shestermanov, Konstantin E. ; Shimanskiy, S. S. ; Sichtermann, E ; Simon, F. ; Singaraju, R. N. ; Skoro, Goran P. ; Smirnov, Nikolai ; Snellings, Raimond ; Sood, Gopika ; Sorensen, Paul Richard ; Sowinski, James ; Speltz, Jeff ; Spinka, Harold. M. ; Srivastava, Brijesh Kumar ; Stadnik, A. ; Stadnik, A. ; Stanislaus, T. D. Shirvel ; Stock, Reinhard ; Stock, Reinhard ; Stolpovsky, Alexander ; Strichanov, Michail Nikolaevič ; Stringfellow, Blair ; Suaide, Alexandre Alarcon do Passo ; Sugarbaker, Evan R. ; Suire, Christophe Pierre ; Šumbera, Michal ; Surrow, Bernd ; Symons, T. J. M. ; Toledo, Alejandro Szanto de ; Szarwas, Piotr ; Tai, An ; Takahashi, Jun ; Tang, A. H. ; Tarnowsky, Terence J. ; Thein, Dylan ; Thomas, James H. ; Timoshenko, Sergei ; Tokarev, Mikhail V. ; Trainor, Thomas A. ; Trentalange, Stephen ; Tribble, Robert E. ; Tsai, Oleg D. ; Ulery, Jason Glyndwr ; Ullrich, Thomas ; Underwood, David G. ; Urkinbaev, Anarbay ; Van Buren, Gene ; Ward, H. ; Watson, J. W. ; Webb, Jason C. ; Wells, R. ; Westfall, G. D. ; Wetzler, Alexander Albert ; Whitten, Charles A. ; Wieman, H. ; Wissink, Scott W. ; Witt, Richard ; Wood, J. ; Wu, J. ; Xu, N. ; Xu, Z. ; Xu, Z. Z. ; Yamamoto, E. ; Yepes, Pablo P. ; Yurevich, Vladimir I. ; Zanevsky, Yuri V. ; Zhang, Haitao ; Zhang, W. M. ; Zhang, Z. P. ; Zolnierczuk, Piotr Adam ; Zoulkarneev, R. ; Zoulkarneeva, Youlia ; Zubarev, A. N. ; Leeuwen, Marco van ; Vander Molen, A. M. ; Varma, Raghava ; Vasilevski, I. M. ; Vasiliev, Alexander Nikolaevich ; Verne, R. ; Vigdor, Steven E. ; Viyogi, Yogendra P. ; Vokal, Stanislav ; Voloshin, S. A. ; Vznuzdaev, Marat ; Waggoner, William T. ; Wang, F. ; Wang, G. ; Wang, X. L. ; Wang, Y. ; Wang, Y. ; Wang, Z. M.
We present a systematic analysis of two-pion interferometry in Au+Au collisions at sqrt[sNN]=200GeV using the STAR detector at Relativistic Heavy Ion Collider. We extract the Hanbury-Brown and Twiss radii and study their multiplicity, transverse momentum, and azimuthal angle dependence. The Gaussianness of the correlation function is studied. Estimates of the geometrical and dynamical structure of the freeze-out source are extracted by fits with blast-wave parametrizations. The expansion of the source and its relation with the initial energy density distribution is studied.
Neuhoff, Jonathan Andreas Hans-Günter ; Kramer, Andreas ; Jörger, Ann-Kathrin ; Berkulian, Olga ; Thavarajasingam, Santhosh G. ; Davies, Benjamin ; Meyer, Bernhard ; Kandziora, Frank ; Shiban, Ehab ; Demetriades, Andreas K. ; Ringel, Florian Alexander
Introduction: The optimal treatment of patients with spinal infections remains a controversial topic. Within Europe, fundamentally different therapeutic concepts are found. Therefore, the aim of this study was to compare the outcome of patients who received surgical vs. antibiotic treatment alone for primary pyogenic spondylodiscitis in an international cohort analysis.
Materials and Methods: The retrospectively compiled databases of tertiary high-volume spine centers served as the baseline for this study. All documented cases of primary spondylodiscitis treated surgically and conservatively in the period of 2017-2022 were included and grouped according to the therapeutic concept: conservative vs. surgical treatment. Independent investigators collected the relevant clinical and radiological data. The primary endpoint of this study was mortality rate; secondary endpoints were relapse rate and persisting neurological deficit.
Results: A total of 392 patients were included in the analysis (155 females with a mean age of 68 years). Of these, 95 cases were treated conservatively (CoT) and 297 cases were treated surgically (SuT). There was no significant difference (p<0.01) related to patient’s disease characteristics: Lumbar was the main location (n=240, CoT 58/ SuT 182, p=0.97) followed by thoracic (n=70, CoT 24/ SuT 46, p=0,03) and cervical (n=47, CoT 7/ SuT 40, p=0.11) region. A multilocular spinal infection was present in 32 patients (CoT 3/ SuT 29, p=0.04). 181 cases (CoT 36/ SuT 145, p=0.06) presented with an epidural abscess. Neurological deficits were recorded in 100 cases (CoT 26/ SuT 74, p=0.63), and septic conditions in 88 cases (CoT 26/ SuT 62, p=0.19). Pre-existing conditions like Diabetes (p=0.57), renal failure (p= 0.97), hepatopathy (p= 0.15), malignoma (p=0.39) or i.v. drug abuse (p=0.93) did also not differ between the groups. The mortality rate of all conservatively treated was 24.2% (23 cases) and 6.7% (20 cases) in all surgically treated patients (p<0.001). A follow-up of ≥ 6 weeks was available in 289 cases (CoT 83, SuT 206 ). In this subset of patients relapse of infection occurred in six (7.2%) and 23 (11.2%) cases in the conservative and early surgical treatment group, respectively (p=0.69). Persisting neurological deficit was recorded in 21 (25.3%) of conservatively treated and 51 (24.8%) of surgically treated cases (p=0.92).
Conclusion: Whereas relapse rates and persisting neurological deficit were not found to differ significantly, the results of this international data analyses, with their respective limitations, clearly support the growing evidence of a significantly reduced mortality rate after surgical therapy for primary pyogenic spondylodiscitis when compared to conservative treatment regimen.
Neuhoff, Jonathan Andreas Hans-Günter ; Kramer, Andreas ; Jörger, Ann-Kathrin ; Berkulian, Olga ; Thavarajasingam, Santhosh G. ; Davies, Benjamin ; Meyer, Bernhard ; Kandziora, Frank ; Shiban, Ehab ; Demetriades, Andreas K. ; Ringel, Florian Alexander
Spinal Tumors / Infections (Spine Parallel Session v.3), September 27, 2023, 8:30 AM - 10:00 AM
Background: The optimal treatment of patients with spinal infections remains a controversial topic. While there is some consensus regarding the indication for surgical intervention in infections with neurologic deficit, significant deformity or progressive disease, other situations remain controversial. Within Europe, fundamentally different therapeutic concepts are found. Therefore, the aim of this study was to compare the outcome of patients who received surgical vs. antibiotic treatment alone for primary pyogenic spondylodiscitis in an international cohort analysis.
Methods: The retrospectively compiled databases of tertiary high-volume spine centers served as the baseline for this study. All documented cases of primary spondylodiscitis treated surgically and conservatively in the period of 2017-2022 were included and grouped according to the therapeutic concept: conservative vs. surgical treatment. Independent investigators collected the relevant clinical and radiological data. The primary endpoint of this study was mortality rate; secondary endpoints were relapse rate and persisting neurological deficit.
Results: A total of 392 patients were included in the analysis (155 females and 237 males with a mean age of 68 years). Of these, 95 cases were treated conservatively (CoT) and 297 cases were treated surgically (SuT). Most of conservatively treated patients were treated in the United Kingdom (CoT 81/ SuT 7), while most of the surgically treated cases were treated in Germany (CoT 14/ SuT 290). There was no significant difference (p<0.01) related to patient’s disease characteristics:
Lumbar was the main location (n=240, CoT 58/ SuT 182, p=0.97) followed by thoracic (n=70, CoT 24/ SuT 46, p=0,03) and cervical (n=47, CoT 7/ SuT 40, p=0.11) region. A multilocular spinal infection was present in 32 patients (CoT 3/ SuT 29, p=0.04). 181 cases (CoT 36/ SuT 145, p=0.06) presented with an epidural abscess. Neurological deficits were recorded in 100 cases (CoT 26/ SuT 74, p=0.63), and septic conditions in 88 cases (CoT 26/ SuT 62, p=0.19). Pre-existing conditions like Diabetes (CoT 20/, SuT 71, p=0.57), renal failure (CoT 19/ SuT 60, p= 0.97), hepatopathy (CoT 4/ SuT 26, p= 0.15), malignoma (CoT 9/ SuT 38, p=0.39) or i.v. drug abuse (CoT 5/, SuT 15, p=0.93) did also not differ between the groups.
The mortality rate of all conservatively treated was 24.2% (23 cases) and 6.7% (20 cases) in all surgically treated patients (p<0.001). A follow-up of ≥ 6 weeks was available in 289 cases (CoT 83, SuT 206 ). In this subset of patients relapse of infection occurred in six (7.2%) and 23 (11.2%) cases in the conservative and early surgical treatment group, respectively (p=0.69). Persisting neurological deficit was recorded in 21 (25.3%) of conservatively treated and 51 (24.8%) of surgically treated cases (p=0.92).
Conclusions: Whereas relapse rates and persisting neurological deficit were not found to differ significantly, the results of this international data analyses, with their respective limitations, clearly support the growing evidence of a significantly reduced mortality rate after surgical therapy for primary pyogenic spondylodiscitis when compared to conservative treatment regimen.
Neuhoff, Jonathan Andreas Hans-Günter ; Berkulian, Olga ; Kramer, Andreas ; Schleicher, Philipp ; Pingel, Andreas ; Kandziora, Frank
Challenges of FAIR phase 0
(2018)
Bai, Mei ; Adonin, Aleksey ; Appel, Sabrina ; Bär, Ralph C. ; Bellachioma, Maria Cristina ; Blell, Udo ; Dimopoulou, Christina ; Franchetti, Giuliano ; Geithner, Oksana ; Gerhard, Peter ; Groening, Lars ; Herfurth, Frank ; Heß, Regina ; Hollinger, Ralph ; Hüther, Hanno C. ; Klingbeil, Harald ; Krämer, Andreas ; Litvinov, Sergey A. ; Maimone, Fabio ; Ondreka, David ; Pyka, Niels ; Reimann, Stephan ; Reiter, Andreas ; Sapinski, Mariusz ; Schlitt, Bernhard ; Schreiber, Gerald ; Schwickert, Marcus ; Severin, Daniel ; Singh, Rahul ; Spiller, Peter J. ; Stadlmann, Jens ; Steck, Markus ; Steinhagen, Ralph J. ; Tinschert, Klaus ; Vossberg, Markus ; Walter, Gertrud ; Weinrich, Udo
After two-year's shutdown, the GSI accelerators plus the latest addition of storage ring CRYRING, will be back into operation in 2018 as the FAIR phase 0 with the goal to fulfill the needs of scientific community and the FAIR accelerators and detector development. Even though GSI has been well known for its operation of a variety of ion beams ranging from proton up to uranium for multi research areas such as nuclear physics, astrophysics, biophysics, material science, the upcoming beam time faces a number of challenges in re-commissioning its existing circular accelerators with brand new control system and upgrade of beam instrumentations, as well as in rising failures of dated components and systems. The cycling synchrotron SIS18 has been undergoing a set of upgrade measures for fulfilling future FAIR operation, among which many measures will also be commissioned during the upcoming beam time. This paper presents the highlights of the challenges such as re-establishing the high intensity heavy ion operation as well as parallel operation mode for serving multi users. The status of preparation including commissioning results will also be reported.
Adams, Joseph R. ; Aggarwal, Madan Mohan ; Ahammed, Zubayer ; Amonett, J. ; Anderson, B.D. ; Arkhipkin, D. ; Averichev, Georgy S. ; Badyal, S.K. ; Bai, Yu ; Balewski, J. ; Barannikova, O. ; Barnby, L.S. ; Baudot, J. ; Bekele, S. ; Belaga, V.V. ; Bellingeri-Laurikainen, A. ; Bellwied, Rene ; Berger, J. ; Bezverkhny, B.I. ; Bharadwaj, S. ; Bhasin, A. ; Bhati, A.K. ; Bhatia, V.S. ; Bichsel, Hans ; Bielcik, J. ; Bielcikova, Jana ; Billmeier, A. ; Bland, L.C. ; Blyth, C.O. ; Blyth, S.-L. ; Bonner, B.E. ; Botje, M. ; Boucham, A. ; Bouchet, J. ; Brandin, A.V. ; Bravar, A. ; Bystersky, M. ; Cadman, R.V. ; Cai, X.Z. ; Caines, Helen Louise ; Calderón de la Barca Sánchez, Manuel ; Castillo Castellanos, Javier Ernesto ; Catu, O. ; Cebra, D. ; Chajecki, Z. ; Chaloupka, Petr ; Chattopadhyay, S. ; Chen, H.F. ; Chen, J.H. ; Chen, Y. ; Cheng, J. ; Cherney, M. ; Chikanian, A. ; Choi, H.A. ; Christie, William ; Coffin, J.P. ; Cormier, Thomas Michael ; Cosentino, M.R. ; Cramer, J.G. ; Crawford, Henry J. ; Das, D. ; Das, S. ; Daugherity, M. ; de Moura, M.M. ; Dedovich, T.G. ; DePhillips, M. ; Derevschikov, Anatoly A. ; Didenko, Lidia ; Dietel, Thomas ; Dogra, S.M. ; Dong, W.J. ; Dong, X. ; Draper, J.E. ; Du, F. ; Dubey, A.K. ; Dunin, V.B. ; Dunlop, James C. ; Dutta Mazumdar, M.R. ; Eckardt, V. ; Edwards, W.R. ; Efimov, L.G. ; Emelianov, V. ; Engelage, Jon M. ; Eppley, Geary Wareham ; Erazmus, B. ; Estienne, M. ; Fachini, P. ; Faivre, J. ; Fatemi, Renee H. ; Fedorisin, J. ; Filimonov, K. ; Filip, P. ; Finch, Evan ; Fine, V. ; Fisyak, Yuri V. ; Fornazier, K.S.F. ; Fu, J. ; Gagliardi, Carl A. ; Gaillard, L. ; Gans, J. ; Ganti, M.S. ; Geurts, Frank ; Ghazikhanian, V. ; Ghosh, P. ; Gonzalez, Johan Enmanuel ; Gos, H. ; Grachov, O. ; Grebenyuk, O. ; Grosnick, David P. ; Guertin, S.M. ; Guo, Y. ; Gupta, Anik ; Gupta, N. ; Gutierrez, T.D. ; Hallman, T.J. ; Hamed, Ahmed M. ; Hardtke, D. ; Harris, John W. ; Heinz, M. ; Henry, T.W. ; Hepplemann, S. ; Hippolyte, Boris ; Hirsch, A. ; Hjort, E. ; Hoffmann, Gerald W. ; Horner, M.J. ; Huang, Huan Zhong ; Huang, Shengli ; Hughes, E.W. ; Humanic, Thomas J. ; Igo, G. ; Ishihara, A. ; Jacobs, P. ; Jacobs, William W. ; Jedynak, M. ; Jiang, H. ; Jones, Peter Graham ; Judd, Eleanor G. ; Kabana, Sonia ; Kang, K. ; Kaplan, M. ; Keane, Declan ; Kechechyan, A. ; Khodyrev, V.Yu. ; Kim, B.C. ; Kiryluk, J. ; Kisiel, A. ; Kislov, E.M. ; Klay, J. ; Klein, S.R. ; Koetke, D.D. ; Kollegger, Thorsten ; Kopytine, M. ; Kotchenda, L. ; Kowalik, K.L. ; Kramer, M. ; Kravtsov, P. ; Kravtsov, V.I. ; Krueger, Keith William ; Kuhn, C. ; Kulikov, A.I. ; Kumar, A. ; Kutuev, R.Kh. ; Kuznetsov, A.A. ; Lamont, Matthew A. C. ; Landgraf, Jeffery M. ; Lange, S. ; Laue, F. ; Lauret, Jerome ; Lebedev, A. ; Lednicky, R. ; Lee, C.-H. ; Lehocka, S. ; LeVine, M.J. ; Li, C. ; Li, Q. ; Li, Y. ; Lin, G. ; Lindenbaum, S.J. ; Lisa, Michael A. ; Liu, F. ; Liu, H. ; Liu, J. ; Liu, L. ; Liu, Q.J. ; Liu, Z. ; Ljubicic, Tonko A. ; Llope, W.J. ; Long, H. ; Longacre, Ronald S. ; Lopez-Noriega, M. ; Love, W.A. ; Lu, Y. ; Ludlam, Thomas ; Lynn, D. ; Ma, G.L. ; Ma, J.G. ; Ma, Y.G. ; Magestro, D. ; Mahajan, Sanjay ; Mahapatra, Durga Prasad ; Majka, R. ; Mangotra, L.K. ; Manweiler, R. ; Margetis, Spyridon ; Markert, Christina ; Martin, L. ; Marx, Jay N. ; Matis, Howard S. ; Matulenko, Yu.A. ; McClain, C.J. ; McShane, T.S. ; Meissner, F. ; Melnick, Yu. ; Meschanin, A. ; Miller, M.L. ; Minaev, N.G. ; Mironov, C. ; Mischke, A. ; Mishra, D.K. ; Mitchell, J. ; Mohanty, Bedangadas ; Molnar, L. ; Moore, C.F. ; Morozov, D.A. ; Munhoz, M.G. ; Nandi, B.K. ; Nayak, S.K. ; Nayak, T.K. ; Nelson, John M. ; Netrakanti, P.K. ; Nikitin, V.A. ; Nogach, L.V. ; Nurushev, S.B. ; Odyniec, Grazyna Janina ; Ogawa, Akio ; Okorokov, Vitaly A. ; Oldenburg, Markus D. ; Olson, D. ; Pal, S.K. ; Panebratsev, Yuri ; Panitkin, Sergei Yurievich ; Pavlinov, A.I. ; Pawlak, T. ; Peitzmann, Thomas ; Perevoztchikov, V. ; Perkins, Chris ; Peryt, W. ; Petrov, V.A. ; Phatak, S.C. ; Picha, R. ; Planinic, Mirko ; Pluta, Jan Marian ; Porile, Norbert T. ; Porter, J. ; Poskanzer, Arthur M. ; Potekhin, M. ; Potrebenikova, E. ; Potukuchi, B.V.K.S. ; Prindle, Duncan J. ; Pruneau, Claude A. ; Putschke, Jörn H. ; Rakness, G. ; Raniwala, R. ; Raniwala, S. ; Ravel, O. ; Ray, Robert L. ; Razin, S.V. ; Reichhold, D. ; Reid, Jeffrey G. ; Reinnarth, J. ; Renault, G. ; Retiere, F. ; Ridiger, A. ; Ritter, Hans Georg ; Roberts, J.B. ; Rogachevskiy, O.V. ; Romero, J.L. ; Rose, A. ; Roy, C. ; Ruan, L. ; Russcher, M.J. ; Sahoo, R. ; Sakrejda, I. ; Salur, Sevil ; Sandweiss, J. ; Sarsour, M. ; Savin, I. ; Sazhin, P.S. ; Schambach, Joachim ; Scharenberg, Rolf Paul ; Schmitz, Norbert ; Schweda, Kai ; Seger, J. ; Seyboth, P. ; Shahaliev, E. ; Shao, M. ; Shao, W. ; Sharma, M. ; Shen, W.Q. ; Shestermanov, K.E. ; Shimanskiy, S.S. ; Sichtermann, E. ; Simon, F. ; Singaraju, R.N. ; Smirnov, Nikolai ; Snellings, Raimond ; Sood, G. ; Sorensen, P. ; Sowinski, James ; Speltz, J. ; Spinka, Harold. M. ; Srivastava, B. ; Stadnik, A. ; Stanislaus, T.D.S. ; Stock, Reinhard ; Stolpovsky, A. ; Strikhanov, M. ; Stringfellow, B. ; Suaide, Alexandre Alarcon do Passo ; Sugarbaker, E. ; Šumbera, Michal ; Surrow, Bernd ; Swanger, M. ; Symons, T.J.M. ; Szanto de Toledo, A. ; Tai, A. ; Takahashi, Jun ; Tang, Aihong ; Tarnowsky, Terence J. ; Thein, D. ; Thomas, James H. ; Timmins, Anthony Robert ; Timoshenko, S. ; Tokarev, M. ; Trainor, T.A. ; Trentalange, Stephen ; Tribble, Robert E. ; Tsai, Oleg D. ; Ulery, J. ; Ullrich, Thomas ; Underwood, David G. ; Van Buren, Gene ; Kolk, Naomi van der ; Leeuwen, Marco van ; Vander Molen, A.M. ; Varma, R. ; Vasilevski, I.M. ; Vasiliev, A.N. ; Vernet, R. ; Vigdor, S.E. ; Viyogi, Y.P. ; Vokal, S. ; Voloshin, Sergei ; Waggoner, W.T. ; Wang, F. ; Wang, G. ; Wang, G. ; Wang, X.L. ; Wang, Y. ; Wang, Y. ; Wang, Z.M. ; Ward, H. ; Watson, J.W. ; Webb, J.C. ; Westfall, Gary D. ; Wetzler, Alexander Albert ; Whitten, Charles A. ; Wieman, Howard ; Wissink, Scott W. ; Witt, Richard ; Wood, J. ; Wu, J. ; Xu, N. ; Xu, Z. ; Xu, Z.Z. ; Yamamoto, E. ; Yepes, P. ; Yoo, I.-K. ; Yurevich, V.I. ; Zborovsky, I. ; Zhang, H. ; Zhang, W.M. ; Zhang, Y. ; Zhang, Z.P. ; Zhong, C. ; Zoulkarneev, R. ; Zoulkarneeva, Youlia ; Zubarev, A.N. ; Zuo, J.X.
We present the first measurements of charge-dependent correlations on angular difference variables η1 − η2 (pseudorapidity) and φ1 − φ2 (azimuth) for primary charged hadrons with transverse momentum 0.15 <= pt <= 2 GeV/c and |η| <= 1.3 from Au–Au collisions at √sNN = 130 GeV. We observe correlation structures not predicted by theory but consistent with evolution of hadron emission geometry with increasing centrality from one-dimensional fragmentation of color strings along the beam direction to an at least two-dimensional hadronization geometry along the beam and azimuth directions of a hadron-opaque bulk medium.