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Lerendegui-Marco, Jorge ; Cortés-Giraldo, Miguel Antonio ; Guerrero Sánchez, Carlos ; Quesada Molina, José Manuel ; Lo Meo, Sergio ; Massimi, Cristian ; Barbagallo, Massimo ; Colonna, Nicola ; Mancusi, Davide ; Mingrone, Federica ; Sabaté-Gilarte, Marta ; Vannini, Gianni ; Vlachoudis, Vasilis ; Aberle, Oliver ; Andrzejewski, Józef ; Audouin, Laurent ; Bacak, Michael ; Balibrea Correa, Javier ; Bečvář, František ; Berthoumieux, Eric ; Billowes, Jonathan ; Bosnar, Damir ; Brown, Adam ; Caamaño, Manuel ; Calviño Tavares, Francisco ; Calviani, Marco ; Cano-Ott, Daniel ; Cardella, Roberto ; Casanovas Hoste, Adrià ; Cerutti, Francesco ; Chen, Yonghao ; Chiaveri, Enrico ; Cortés Rossell, Guillem Pere ; Cosentino, Luigi ; Damone, Lucia Anna ; Diakaki, Maria ; Domingo-Pardo, César ; Dressler, Rugard ; Dupont, Emmeric ; Durán, Ignacio ; Fernández Domínguez, Beatriz ; Ferrari, Alfredo ; Ferreira, Pedro G. ; Finocchiaro, Paolo ; Göbel, Kathrin ; Gómez Hornillos, María Belén ; García Ríos, Aczel Regino ; Gawlik, Aleksandra ; Gilardoni, Simone ; Glodariu, Tudor ; Gonçalves, Isabel Maria Ferro ; González Romero, Enrique Miguel ; Griesmayer, Erich ; Gunsing, Frank ; Harada, Hideo ; Heinitz, Stephan ; Heyse, Jan ; Jenkins, David ; Jericha, Erwin ; Käppeler, Franz ; Kadi, Yacine ; Kalamara, Antigoni ; Kavrigin, Pavel ; Kimura, Atsushi ; Kivel, Nikolay ; Kokkoris, Michael ; Krtička, Milan ; Kurtulgil, Cem Deniz ; Leal Cidoncha, Esther ; Lederer, Claudia ; Leeb, Helmut ; Lonsdale, Sarah Jane ; Macina, Daniela ; Marganiec, Justyna ; Martı́nez, Trinitario ; Masi, Alessandro ; Mastinu, Pierfrancesco ; Mastromarco, Mario ; Maugeri, Emilio Andrea ; Mazzone, Annamaria ; Mendoza Cembranos, Emilio ; Mengoni, Alberto ; Milazzo, Paolo Maria ; Musumarra, Agatino ; Negret, Alexandru ; Nolte, Ralf ; Oprea, Andreea ; Patronis, Nikolas ; Pavlik, Andreas ; Perkowski, Jarosław ; Porras Sánchez, José Ignacio ; Praena, Javier ; Radeck, Désirée ; Rauscher, Thomas ; Reifarth, René ; Rout, Prakash Chandra ; Rubbia, Carlo ; Ryan, James A. ; Saxena, Alok ; Schillebeeckx, Peter ; Schumann, Dorothea ; Smith, Alastair Gavin ; Sosnin, Nikolay V. ; Stamatopoulos, Athanasios ; Tagliente, Giuseppe ; Taı́n Enríquez, José Luis ; Tarifeño-Saldivia, Ariel ; Tassan-Got, Laurent ; Valenta, Stanislav ; Variale, Vincenzo ; Vaz, Pedro ; Ventura, Alberto ; Vlastou, Rosa ; Wallner, Anton ; Warren, Stephen J. ; Woods, Philip John ; Wright, Tobias ; Žugec, Petar
Monte Carlo (MC) simulations are an essential tool to determine fundamental features of a neutron beam, such as the neutron flux or the γ-ray background, that sometimes can not be measured or at least not in every position or energy range. Until recently, the most widely used MC codes in this field had been MCNPX and FLUKA. However, the Geant4 toolkit has also become a competitive code for the transport of neutrons after the development of the native Geant4 format for neutron data libraries, G4NDL. In this context, we present the Geant4 simulations of the neutron spallation target of the n_TOF facility at CERN, done with version 10.1.1 of the toolkit. The first goal was the validation of the intra-nuclear cascade models implemented in the code using, as benchmark, the characteristics of the neutron beam measured at the first experimental area (EAR1), especially the neutron flux and energy distribution, and the time distribution of neutrons of equal kinetic energy, the so-called Resolution Function. The second goal was the development of a Monte Carlo tool aimed to provide useful calculations for both the analysis and planning of the upcoming measurements at the new experimental area (EAR2) of the facility.
Diez-Perez, Adolfo ; Brandi, Maria Luisa ; Al‑Daghri, Nasser ; Branco, Jaime C. ; Bruyère, Olivier ; Cavalli, Loredana ; Cooper, Cyrus ; Cortet, Bernard ; Dawson-Hughes, Bess ; Dimai, Hans Peter ; Gonnelli, Stefano ; Hadji, Peyman ; Halbout, Philippe ; Kaufman, Jean‑Marc ; Kurth, Andreas Alois ; Locquet, Medea ; Maggi, Stefania ; Matijevic, Radmila ; Reginster, Jean‑Yves ; Rizzoli, René ; Thierry, Thomas
Purpose: The purpose of this paper was to review the available approaches for bone strength assessment, osteoporosis diagnosis and fracture risk prediction, and to provide insights into radiofrequency echographic multi spectrometry (REMS), a non-ionizing axial skeleton technique.
Methods: A working group convened by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis met to review the current image-based methods for bone strength assessment and fracture risk estimation, and to discuss the clinical perspectives of REMS.
Results: Areal bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) is the consolidated indicator for osteoporosis diagnosis and fracture risk assessment. A more reliable fracture risk estimation would actually require an improved assessment of bone strength, integrating also bone quality information. Several different approaches have been proposed, including additional DXA-based parameters, quantitative computed tomography, and quantitative ultrasound. Although each of them showed a somewhat improved clinical performance, none satisfied all the requirements for a widespread routine employment, which was typically hindered by unclear clinical usefulness, radiation doses, limited accessibility, or inapplicability to spine and hip, therefore leaving several clinical needs still unmet. REMS is a clinically available technology for osteoporosis diagnosis and fracture risk assessment through the estimation of BMD on the axial skeleton reference sites. Its automatic processing of unfiltered ultrasound signals provides accurate BMD values in view of fracture risk assessment.
Conclusions: New approaches for improved bone strength and fracture risk estimations are needed for a better management of osteoporotic patients. In this context, REMS represents a valuable approach for osteoporosis diagnosis and fracture risk prediction.
Bauersachs, Rupert ; Gerlach, Horst E. ; Heinken, Andreas ; Hoffmann, Ulrich ; Langer, Florian ; Noppeney, Thomas ; Pittrow, David ; Klotsche, Jens ; Rabe, Eberhard
Objective: Management and outcomes of superficial vein thrombosis (SVT) are highly variable and not well described. Therefore, the INvestigating SIGnificant Health TrendS in the management of SVT (INSIGHTS-SVT) study collected prospective data under real life conditions.
Methods: Prospective observational study of objectively confirmed acute isolated SVT. The primary outcome was a composite of symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE), and extension or recurrence of SVT at three months. The primary safety outcome was clinically relevant bleeding.
Results: A total of 1 150 patients were included (mean age 60.2 ± 14.7 years; 64.9% women; mean BMI 29.4 ± 6.3 kg/m2). SVT was below the knee in 54.5%, above the knee in 26.7%, above and below the knee in 18.8%. At baseline, 93.6% received pharmacological treatment (65.7% fondaparinux, 23.2% heparins, 4.3% direct oral anticoagulants [DOACs], 14.5% analgesics), 77.0% compression treatment, and 1.9% surgery; 6.4% did not receive any anticoagulation. The primary outcome occurred in 5.8%; 4.7% had recurrent or extended SVT, 1.7% DVT, and 0.8% PE. Clinically relevant non-major bleeding occurred in 1.2% and major bleeding in 0.3%. Complete clinical recovery of SVT was reported in 708 patients (62.4%). Primary outcome adjusted by propensity score and for treatment duration was lower with fondaparinux compared with low molecular weight heparin (4.4% vs. 9.6%; hazard ratio [HR] 0.51; 95% confidence interval [CI] 0.3 - 0.9; p = .017). On multivariable analysis, associated factors for primary outcome included another SVT prior to the present SVT event (HR 2.3), age per year (HR 0.97), duration of drug treatment per week (HR 0.92), and thrombus length (HR 1.03).
Conclusion: At three month follow up, patients with isolated SVT are at risk of thromboembolic complications (mainly recurrent or extended SVT), despite anticoagulation. In this real life study, about one third had received either heparins, oral anticoagulants, or no anticoagulation.
Spyrantis, Andrea ; Woebbecke, Tirza ; Rueß, Daniel Friedrich ; Constantinescu, Anne ; Gierich, Andreas ; Luyken, Klaus ; Visser-Vandewalle, Veerle ; Herrmann, Eva ; Geßler, Florian ; Czabanka, Marcus Alexander ; Treuer, Harald ; Ruge, Maximilian Ingolf ; Freiman, Thomas Michael
Background: The development of robotic systems has provided an alternative to frame-based stereotactic procedures. The aim of this experimental phantom study was to compare the mechanical accuracy of the Robotic Surgery Assistant (ROSA) and the Leksell stereotactic frame by reducing clinical and procedural factors to a minimum.
Methods: To precisely compare mechanical accuracy, a stereotactic system was chosen as reference for both methods. A thin layer CT scan with an acrylic phantom fixed to the frame and a localizer enabling the software to recognize the coordinate system was performed. For each of the five phantom targets, two different trajectories were planned, resulting in 10 trajectories. A series of five repetitions was performed, each time based on a new CT scan. Hence, 50 trajectories were analyzed for each method. X-rays of the final cannula position were fused with the planning data. The coordinates of the target point and the endpoint of the robot- or frame-guided probe were visually determined using the robotic software. The target point error (TPE) was calculated applying the Euclidian distance. The depth deviation along the trajectory and the lateral deviation were separately calculated.
Results: Robotics was significantly more accurate, with an arithmetic TPE mean of 0.53 mm (95% CI 0.41–0.55 mm) compared to 0.72 mm (95% CI 0.63–0.8 mm) in stereotaxy (p < 0.05). In robotics, the mean depth deviation along the trajectory was −0.22 mm (95% CI −0.25 to −0.14 mm). The mean lateral deviation was 0.43 mm (95% CI 0.32–0.49 mm). In frame-based stereotaxy, the mean depth deviation amounted to −0.20 mm (95% CI −0.26 to −0.14 mm), the mean lateral deviation to 0.65 mm (95% CI 0.55–0.74 mm).
Conclusion: Both the robotic and frame-based approach proved accurate. The robotic procedure showed significantly higher accuracy. For both methods, procedural factors occurring during surgery might have a more relevant impact on overall accuracy.
Wenzel, Gentiana ; Sarnes, Petra ; Büchner, Andreas ; Stöver, Timo ; Lesinski-Schiedat, Anke ; Lenarz, Thomas
Meeting Abstract : 82. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie. Freiburg i. Br., 01.-05.06.2011.
Ca. 3 Millionen Erwachsene in der Bundesrepublik Deutschland leiden unter Tinnitus, wobei eine bei jedem dieser Patienten zur Heilung führende Therapie bisher noch nicht existiert. Ansatzpunkt einer neuartigen Therapie ist die Wiederherstellung des normalen elektrischen Entladungsmusters im Hörnerv mittels elektrischer Stimulation. Hiermit berichten wir über unsere ersten Erfahrungen mit dem Tinnelec, einem Implantat mit einer einzelnen Stimulations-Elektrode die in der Rundfensternische platziert wird.
Zurzeit haben wir 4 einseitig ertaubten Patienten mit Tinnitus auf dem betroffenen Ohr jeweils ein Tinnelec-System implantiert. Die Dauer des Tinnitus betrug mindestens ein Jahr und gängige Tinnitus-Therapien wie z.B. Infusionstherapie waren erfolglos geblieben. Ein psychogener Tinnitus wurde ausgeschlossen. Der durch den Tinnitus verursachte Leidensdruck wurde anhand einer VAS Scala (Visuelle Analog Scala) und eines Tinnitus-Handicap-Inventory (THI) Fragebogens beurteilt. Die Reizapplikation betrug mind. 4 Stunden täglich. Als Stimulationsparameter wurde eine Reizmusterannäherung an den Tinnitus angestrebt.
Bei drei Patienten wurde unter der Stimulation der Tinnitus erträglicher, eine zeitweise komplette Unterdrückung des Tinnitus schon innerhalb der ersten Therapie-Wochen wurde jedoch nur in einem der Fälle berichtet. Diese Ergebnisse wurden auch durch das THI und VAS unterstützt.
Die Tinnelec-Implantation erscheint für Tinnitus Erfolg versprechend zu sein. Weitere Studien bei Tinnitus-Patienten ohne zusätzliche Hörbeeinträchtigung sind jedoch notwendig bis endgültige Schlussfolgerungen betreffend dieses Implantats gezogen werden können. In jedem Fall bleibt die Option einer Cochlea-Implantation im selben Ohr, nach Explantation des Tinnelec, bestehen.
Wilde, Anne-Christin ; Lieb, Charlotte ; Leicht, Elise ; Greverath, Lena Maria ; Steinhagen, Lara Marleen ; Wald de Chamorro, Nina ; Petersen, Jörg ; Hofmann, Wolf-Peter ; Hinrichsen, Holger ; Heyne, Renate ; Berg, Thomas ; Naumann, Uwe ; Schwenzer, Jeannette ; Vermehren, Johannes ; Geier, Andreas ; Tacke, Frank ; Müller, Tobias
Background: Clinical practice guidelines for patients with primary biliary cholangitis (PBC) have been recently revised and implemented for well-established response criteria to standard first-line ursodeoxycholic acid (UDCA) therapy at 12 months after treatment initiation for the early identification of high-risk patients with inadequate treatment responses who may require treatment modification. However, there are only very limited data concerning the real-world clinical management of patients with PBC in Germany. Objective: The aim of this retrospective multicenter study was to evaluate response rates to standard first-line UDCA therapy and subsequent Second-line treatment regimens in a large cohort of well-characterized patients with PBC from 10 independent hepatological referral centers in Germany prior to the introduction of obeticholic acid as a licensed second-line treatment option. Methods: Diagnostic confirmation of PBC, standard first-line UDCA treatment regimens and response rates at 12 months according to Paris-I, Paris-II, and Barcelona criteria, the follow-up cut-off alkaline phosphatase (ALP) ≤ 1.67 × upper limit of normal (ULN) and the normalization of bilirubin (bilirubin ≤ 1 × ULN) were retrospectively examined between June 1986 and March 2017. The management and hitherto applied second-line treatment regimens in patients with an inadequate response to UDCA and subsequent response rates at 12 months were also evaluated. Results: Overall, 480 PBC patients were included in this study. The median UDCA dosage was 13.2 mg UDCA/kg bodyweight (BW)/d. Adequate UDCA treatment response rates according to Paris-I, Paris-II, and Barcelona criteria were observed in 91, 71.3, and 61.3% of patients, respectively. In 83.8% of patients, ALP ≤ 1.67 × ULN were achieved. A total of 116 patients (24.2%) showed an inadequate response to UDCA according to at least one criterion. The diverse second-line treatment regimens applied led to significantly higher response rates according to Paris-II (35 vs. 60%, p = 0.005), Barcelona (13 vs. 34%, p = 0.0005), ALP ≤ 1.67 × ULN and bilirubin ≤ 1 × ULN (52.1 vs. 75%, p = 0.002). The addition of bezafibrates appeared to induce the strongest beneficial effect in this cohort (Paris II: 24 vs. 74%, p = 0.004; Barcelona: 50 vs. 84%, p = 0.046; ALP < 1.67 × ULN and bilirubin ≤ 1 × ULN: 33 vs. 86%, p = 0.001). Conclusion: Our large retrospective multicenter study confirms high response rates following UDCA first-line standard treatment in patients with PBC and highlights the need for close monitoring and early treatment modification in high-risk patients with an insufficient response to UDCA since early treatment modification significantly increases subsequent response rates of these patients.
Medema, Marnix H. ; Kottmann, Renzo ; Yilmaz, Pelin ; Cummings, Matthew ; Biggins, John B. ; Kai, Blin ; de Bruijn, Irene ; Chooi, Yit Heng ; Claesen, Jan ; Coates, R. Cameron ; Cruz-Morales, Pablo ; Duddela, Srikanth ; Düsterhus, Stephanie ; Edwards, Daniel J. ; Fewer, David P. ; Garg, Neha ; Geiger, Christoph ; Gomez-Escribano, Juan Pablo ; Greule, Anja ; Hadjithomas, Michalis ; Haines, Anthony S. ; Helfrich, Eric J. N. ; Hillwig, Matthew L. ; Ishida, Keishi ; Jones, Adam C. ; Jones, Carla S. ; Jungmann, Katrin ; Kegler, Carsten ; Kim, Hyun Uk ; Kötter, Peter ; Krug, Daniel ; Masschelein, Joleen ; Melnik, Alexey V. ; Mantovan, Simone M. ; Monroe, Emily A. ; Moore, Marcus ; Moss, Nathan ; Nützmann, Hans-Wilhelm ; Pan, Guohui ; Pati, Amrita ; Petras, Daniel ; Reen, F. Jerry ; Rosconi, Federico ; Rui, Zhe ; Tian, Zhenhua ; Tobias, Nicholas J. ; Tsunematsu, Yuta ; Wiemann, Philipp ; Wyckoff, Elizabeth ; Yan, Xiaohui ; Yim, Grace ; Yu, Fengan ; Xie, Yunchang ; Aigle, Bertrand ; Apel, Alexander K. ; Balibar, Carl J. ; Balskus, Emily P. ; Barona-Gómez, Francisco ; Bechthold, Andreas ; Bode, Helge Björn ; Borriss, Rainer ; Brady, Sean F. ; Brakhage, Axel A. ; Caffrey, Patrick ; Cheng, Yi-Qiang ; Clardy, Jon ; Cox, Russell J. ; De Mot, René ; Donadio, Stefano ; Donia, Mohamed S. ; van der Donk, Wilfred A. ; Dorrestein, Pieter C. ; Doyle, Sean ; Driessen, Arnold J. M. ; Ehling-Schulz, Monika ; Entian, Karl-Dieter ; Fischbach, Michael A. ; Gerwick, Lena ; Gerwick, William H. ; Gross, Harald ; Gust, Bertolt ; Hertweck, Christian ; Höfte, Monica ; Jensen, Susan E. ; Ju, Jianhua ; Katz, Leonard ; Kaysser, Leonard ; Klassen, Jonathan L. ; Keller, Nancy P. ; Kormanec, Jan ; Kuipers, Oscar P. ; Kuzuyama, Tomohisa ; Kyrpides, Nikos C. ; Kwon, Hyung-Jin ; Lautru, Sylvie ; Lavigne, Rob ; Lee, Chia Y. ; Linquan, Bai ; Liu, Xinyu ; Liu, Wen ; Luzhetskyy, Andriy ; Mahmud, Taifo ; Mast, Yvonne ; Méndez, Carmen ; Metsä-Ketelä, Mikko ; Micklefield, Jason ; Mitchell, Douglas A. ; Moore, Bradley S. ; Moreira, Leonilde M. ; Müller, Rolf ; Neilan, Brett A. ; Nett, Markus ; Nielsen, Jens ; O’Gara, Fergal ; Oikawa, Hideaki ; Osbourn, Anne ; Osburne, Marcia S. ; Ostash, Bohdan ; Payne, Shelley M. ; Pernodet, Jean-Luc ; Petricek, Miroslav ; Piel, Jörn ; Ploux, Olivier ; Raaijmakers, Jos M. ; Salas, José A. ; Schmitt, Esther K. ; Scott, Barry ; Seipke, Ryan F. ; Shen, Ben ; Sherman, David H. ; Sivonen, Kaarina ; Smanski, Michael J. ; Sosio, Margherita ; Stegmann, Evi ; Süssmuth, Roderich D. ; Tahlan, Kapil ; Thomas, Christopher M. ; Tang, Yi ; Truman, Andrew W. ; Viaud, Muriel ; Walton, Jonathan D. ; Walsh, Christopher T. ; Weber, Tilmann ; van Wezel, Gilles P. ; Wilkinson, Barrie ; Willey, Joanne M. ; Wohlleben, Wolfgang ; Wright, Gerard D. ; Ziemert, Nadine ; Zhang, Changsheng ; Zotchev, Sergey B. ; Breitling, Rainer ; Takano, Eriko ; Glöckner, Frank Oliver
A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.
Kurth, Florian Michael ; Develoux, Michel ; Mechain, Matthieu ; Malvy, Denis ; Clerinx, Jan ; Antinori, Spinello ; Gjørup, Ida E. ; Gascon, Joaquím ; Mørch, Kristine ; Nicastri, Emanuele ; Ramharter, Michael ; Bartoloni, Alessandro ; Visser, Leo ; Rolling, Thierry ; Zanger, Philipp ; Calleri, Guido ; Salas‑Coronas, Joaquín ; Nielsen, Henrik ; Just‑Nübling, Gudrun ; Neumayr, Andreas ; Hachfeld, Anna ; Schmid, Matthias L. ; Antonini, Pietro ; Lingscheid, Tilman ; Kern, Peter ; Kapaun, Annette ; Cunha, José Saraiva da ; Pongratz, Peter ; Soriano‑Arandes, Antoni ; Schunk, Mirjam ; Suttorp, Norbert ; Hatz, Christoph ; Zoller, Thomas
Background: Malaria remains one of the most serious infections for travellers to tropical countries. Due to the lack of harmonized guidelines a large variety of treatment regimens is used in Europe to treat severe malaria.
Methods: The European Network for Tropical Medicine and Travel Health (TropNet) conducted an 8-year, multicentre, observational study to analyse epidemiology, treatment practices and outcomes of severe malaria in its member sites across Europe. Physicians at participating TropNet centres were asked to report pseudonymized retrospective data from all patients treated at their centre for microscopically confirmed severe Plasmodium falciparum malaria according to the 2006 WHO criteria.
Results: From 2006 to 2014 a total of 185 patients with severe malaria treated in 12 European countries were included. Three patients died, resulting in a 28-day survival rate of 98.4%. The majority of infections were acquired in West Africa (109/185, 59%). The proportion of patients treated with intravenous artesunate increased from 27% in 2006 to 60% in 2013. Altogether, 56 different combinations of intravenous and oral drugs were used across 28 study centres. The risk of acute renal failure (36 vs 17% p = 0.04) or cerebral malaria (54 vs 20%, p = 0.001) was significantly higher in patients ≥60 years than in younger patients. Respiratory distress with the need for mechanical ventilation was significantly associated with the risk of death in the study population (13 vs 0%, p = 0.001). Post-artemisinin delayed haemolysis was reported in 19/70 (27%) patients treated with intravenous artesunate.
Conclusion: The majority of patients with severe malaria in this study were tourists or migrants acquiring the infection in West Africa. Intravenous artesunate is increasingly used for treatment of severe malaria in many European treatment centres and can be given safely to European patients with severe malaria. Patients treated with intravenous artesunate should be followed up to detect and manage late haemolytic events.
Kennedy, Eamonn ; Vadlamani, Shashank ; Lindsey, Hannah M. ; Lei, Pui-Wa ; Jo-Pugh, Mary ; Adamson, Maheen ; Alda, Martin ; Alonso-Lana, Silvia ; Ambrogi, Sonia ; Anderson, Tim J. ; Arango, Celso ; Asarnow, Robert F. ; Avram, Mihai ; Ayesa-Arriola, Rosa ; Babikian, Talin ; Banaj, Nerisa ; Bird, Laura J. ; Borgwardt, Stefan ; Brodtmann, Amy ; Brosch, Katharina ; Caeyenberghs, Karen ; Calhoun, Vince D. ; Chiaravalloti, Nancy D. ; Cifu, David X. ; Crespo-Facorro, Benedicto ; Dalrymple-Alford, John C. ; Dams-O’Connor, Kristen ; Dannlowski, Udo ; Darby, David ; Davenport, Nicholas ; DeLuca, John ; Díaz-Caneja, Covadonga M. ; Disner, Seth G. ; Dobryakova, Ekaterina ; Ehrlich, Stefan ; Esopenko, Carrie ; Ferrarelli, Fabio ; Frank, Lea E. ; Franz, Carol ; Fuentes-Claramonte, Paola ; Genova, Helen ; Giza, Christopher C. ; Goltermann, Janik ; Grotegerd, Dominik ; Gruber, Marius ; Gutiérrez-Zotes, Alfonso ; Ha, Minji ; Haavik, Jan ; Hinkin, Charles ; Hoskinson, Kristen R. ; Hubl, Daniela ; Irimia, Andrei ; Jansen, Andreas ; Kaess, Michael ; Kang, Xiaojian ; Kenney, Kimbra ; Keřková, Barbora ; Khlif, Mohamed Salah ; Kim, Minah ; Kindler, Jochen ; Kircher, Tilo ; Knı́žková, Karolina ; Kolskår, Knut K. ; Krch, Denise ; Kremen, William S. ; Kuhn, Taylor ; Kumari, Veena ; Kwon, Jun Soo ; Langella, Roberto ; Laskowitz, Sarah ; Lee, Jungha ; Lengenfelder, Jean ; Liebel, Spencer W. ; Liou-Johnson, Victoria ; Lippa, Sara M. ; Løvstad, Marianne ; Lundervold, Astri ; Marotta, Cassandra ; Marquardt, Craig A. ; Mattos, Paulo ; Mayeli, Ahmad ; McDonald, Carrie R. ; Meinert, Susanne ; Melzer, Tracy R. ; Merchán Naranjo, Jessica ; Michel, Chantal ; Morey, Rajendra A. ; Mwangi, Benson ; Myall, Daniel J. ; Nenadić, Igor ; Newsome, Mary R. ; Nunes, Abraham ; O’Brien, Terence J. ; Oertel, Viola ; Ollinger, John ; Olsen, Alexander ; Ortiz Garcı́a de la Foz, Victor ; Ozmen, Mustafa ; Pardoe, Heath ; Parent, Marise ; Piras, Fabrizio ; Piras, Federica ; Pomarol-Clotet, Edith ; Repple, Jonathan ; Richard, Geneviève ; Rodriguez, Jonathan ; Rodriguez, Mabel ; Rootes-Murdy, Kelly ; Rowland, Jared ; Ryan, Nicholas P. ; Salvador, Raymond ; Sanders, Anne-Marthe ; Schmidt, André ; Soares, Jair C. ; Spalleta, Gianfranco ; Španiel, Filip ; Stasenko, Alena ; Stein, Frederike ; Straube, Benjamin ; Thames, April ; Thomas-Odenthal, Florian ; Thomopoulos, Sophia I. ; Tone, Erin ; Torres, Ivan ; Troyanskaya, Maya ; Turner, Jessica A. ; Ulrichsen, Kristine M. ; Umpierrez, Guillermo ; Vilella, Elisabet ; Vivash, Lucy ; Walker, William C. ; Werden, Emilio ; Westlye, Lars T. ; Wild, Krista ; Wroblewski, Adrian ; Wu, Mon-Ju ; Wylie, Glenn R. ; Yatham, Lakshmi N. ; Zunta-Soares, Giovana B. ; Thompson, Paul M. ; Tate, David F. ; Hillary, Frank G. ; Dennis, Emily L. ; Wilde, Elisabeth A.
Investigators in the cognitive neurosciences have turned to Big Data to address persistent replication and reliability issues by increasing sample sizes, statistical power, and representativeness of data. While there is tremendous potential to advance science through open data sharing, these efforts unveil a host of new questions about how to integrate data arising from distinct sources and instruments. We focus on the most frequently assessed area of cognition - memory testing - and demonstrate a process for reliable data harmonization across three common measures. We aggregated raw data from 53 studies from around the world which measured at least one of three distinct verbal learning tasks, totaling N = 10,505 healthy and brain-injured individuals. A mega analysis was conducted using empirical bayes harmonization to isolate and remove site effects, followed by linear models which adjusted for common covariates. After corrections, a continuous item response theory (IRT) model estimated each individual subject’s latent verbal learning ability while accounting for item difficulties. Harmonization significantly reduced inter-site variance by 37% while preserving covariate effects. The effects of age, sex, and education on scores were found to be highly consistent across memory tests. IRT methods for equating scores across AVLTs agreed with held-out data of dually-administered tests, and these tools are made available for free online. This work demonstrates that large-scale data sharing and harmonization initiatives can offer opportunities to address reproducibility and integration challenges across the behavioral sciences.
Kastirke, Gregor ; Schöffler, Markus S. ; Weller, Miriam ; Rist, Jonas ; Boll, Rebecca ; Anders, Nils ; Baumann, Thomas M. ; Eckart, Sebastian ; Erk, Benjamin ; De Fanis, Alberto ; Fehre, Kilian ; Gatton, Averell ; Grundmann, Sven Eric ; Grychtol, Patrik ; Hartung, Alexander ; Hofmann, Max ; Ilchen, Markus ; Janke, Christian Sören ; Kircher, Max ; Kunitski, Maksim ; Li, Xiang ; Mazza, Tommaso ; Melzer, Niklas ; Montano, Jacobo ; Music, Valerija ; Nalin, Giammarco ; Ovcharenko, Yevheniy ; Pier, Andreas ; Rennhack, Nils ; Rivas, Daniel E. ; Dörner, Reinhard ; Rolles, Daniel ; Rudenko, Artem ; Schmidt, Philipp ; Siebert, Juliane ; Strenger, Nico ; Trabert, Daniel ; Vela-Perez, Isabel ; Wagner, Rene ; Weber, Thorsten ; Williams, Joshua B. ; Ziolkowski, Pawel ; Schmidt, Lothar ; Czasch, Achim ; Trinter, Florian ; Meyer, Michael ; Ueda, Kiyoshi ; Demekhin, Philipp V. ; Jahnke, Till
A central motivation for the development of x-ray free-electron lasers has been the prospect of time-resolved single-molecule imaging with atomic resolution. Here, we show that x-ray photoelectron diffraction—where a photoelectron emitted after x-ray absorption illuminates the molecular structure from within—can be used to image the increase of the internuclear distance during the x-ray-induced fragmentation of an O2 molecule. By measuring the molecular-frame photoelectron emission patterns for a two-photon sequential K-shell ionization in coincidence with the fragment ions, and by sorting the data as a function of the measured kinetic energy release, we can resolve the elongation of the molecular bond by approximately 1.2 a.u. within the duration of the x-ray pulse. The experiment paves the road toward time-resolved pump-probe photoelectron diffraction imaging at high-repetition-rate x-ray free-electron lasers.