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1. Integrative Analyses of Circulating Proteins and Metabolites Reveal Sex Differences in the Associations with Cardiac Function among DCM Patients

Author

Anke Hannemann, Sabine Ameling, Kristin Lehnert, Marcus Dörr, Stephan B. Felix, Matthias Nauck, Muna N. Al-Noubi, Frank Schmidt, Jan Haas, Benjamin Meder, Uwe Völker, Nele Friedrich, and Elke Hammer

Subjects
DCM, proteomics, metabolomics, phenotype association, correlation, OLINK, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Dilated cardiomyopathy (DCM) is characterized by reduced left ventricular ejection fraction (LVEF) and left or biventricular dilatation. We evaluated sex-specific associations of circulating proteins and metabolites with structural and functional heart parameters in DCM. Plasma samples (297 men, 71 women) were analyzed for proteins using Olink assays (targeted analysis) or LC-MS/MS (untargeted analysis), and for metabolites using LC MS/MS (Biocrates AbsoluteIDQ p180 Kit). Associations of proteins (n = 571) or metabolites (n = 163) with LVEF, measured left ventricular end diastolic diameter (LVEDDmeasured), and the dilation percentage of LVEDD from the norm (LVEDDacc. to HENRY) were examined in combined and sex-specific regression models. To disclose protein–metabolite relations, correlation analyses were performed. Associations between proteins, metabolites and LVEF were restricted to men, while associations with LVEDD were absent in both sexes. Significant metabolites were validated in a second independent DCM cohort (93 men). Integrative analyses demonstrated close relations between altered proteins and metabolites involved in lipid metabolism, inflammation, and endothelial dysfunction with declining LVEF, with kynurenine as the most prominent finding. In DCM, the loss of cardiac function was reflected by circulating proteins and metabolites with sex-specific differences. Our integrative approach demonstrated that concurrently assessing specific proteins and metabolites might help us to gain insights into the alterations associated with DCM.

Published
2024
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2. Telemedical cardiac risk assessment by implantable cardiac monitors in patients after myocardial infarction with autonomic dysfunction (SMART-MI-DZHK9): a prospective investigator-initiated, randomised, multicentre, open-label, diagnostic trial

Author

Axel Bauer, ProfMD, Nikolay Sappler, MD, Lukas von Stülpnagel, PhD, Mathias Klemm, MD, Michael Schreinlechner, MD, Felix Wenner, MD, Johannes Schier, MD, Amani Al Tawil, MSc, Theresa Dolejsi, MD, Aresa Krasniqi, MD, Elodie Eiffener, MSc, Christa Bongarth, MD, Markus Stühlinger, MD, Martin Huemer, MD, Tommaso Gori, ProfMD, Reza Wakili, ProfMD, Riza Sahin, MD, Robert Schwinger, MD, Matthias Lutz, MD, Armin Luik, MD, Nele Gessler, MD, Peter Clemmensen, ProfMD, Axel Linke, ProfMD, Lars S Maier, ProfMD, Martin Hinterseer, MD, Mathias C Busch, MD, Florian Blaschke, MD, Stefan Sack, ProfMD, Carsten Lennerz, MSc, Manuela Licka, MD, Roland R Tilz, ProfMD, Christian Ukena, MD, Joachim R Ehrlich, ProfMD, Markus Zabel, ProfMD, Georg Schmidt, ProfMD, Ulrich Mansmann, Prof, Stefan Kääb, ProfMD, Konstantinos D Rizas, MD, Steffen Massberg, ProfMD, Andreas May, Peter Seitzer, Roland Schmidt, Dritan Keta, Viktoria Janke, Christian Schläger, Elisabeth André, Niels Brandt, Alexandra Schön, Alfred Zollner, Luisa Freyer, Wolfgang Hamm, Johannes Beil, Anna Katharina Strüven, Anja Loew, Stephanie Fichtner, Philipp Lange, Aresa Krasniqi, Ulrich Grabmeier, Heidi Estner, Philipp Bengel, Lars Lüthje, Aleksandra Kirova, Thomas Fischer, Leonard Bergau, Jonas Herting, Simon Schlögl, Helge Haarmann, Klaudia Schlögl (Illes), Ekrem Uecer, Sabine Sag, Maria Tafelmeier, Carsten Jungbauer, Sabine Fredersdorf-Hahn, Christina Strack, Benedikt Seither, Joachim Seegers, Dominic Millenaar, Jan Wintrich, Patrick Fischer, Axel Buob, Amjad Razouk, Thomas Demming, Johanne Frank, Constantin Kühl, Ulrike Ellendt, Sarah Sandrock, Julia Gänsbacher, Janosch Cupa, Daniel Sinnecker, Karl-Ludwig Laugwitz, Alexander Steger, Anna Berkefeld, Karin Schinke, Petra Barthel, Michael Dommasch, Maiwand Amadei, Gerhard Hindricks, Danilo Obradovic, Michael Döring, Kerstin Bode, Sebastian Hilbert, Susanne Löbe, Helge Knopp, Sebastian König, Silke John, Katharina Schöne, Philipp Hartung, Christian Binner, Christine Meyer-Zürn, Martin Duckheim, Christian Eick, Fabian Simpfle, Jürgen Schreieck, Lars Mizera, Verena Tscholl, Lisa Steinbeck, Nadija Güc, Anne-Sophie Schatz, Philipp Attanasio, Andrea Heuberger, Mattias Roser, Barbara Bellmann, Patrick Nagel, Sebastian Biewener, Saba Suhail, Benjamin Juri, Christian Meyer, Stephan Wiilems, Christiane Jungen, Susanne Schmitt, Paula Münkerer, Julia Vogler, Lukas Kaiser, Benjamin Schäffer, Moritz Nies, Tobias Tönnis, Nina Fluschnik, Hanno Grahn, Christoph Waldeyer, Shinwan Kany, Nils Arne Sörensen, Simon Winkelmann, Özge Akbulak, Nils Arne Gosau, Tilman Würger, Natalie Arnold, Nele Geßler, Alexander Jobs, Paula Münkler, Stefan Rausch, Jelena Köster, Ben Brüggemann, Amr Abdin, Christian Wacker, Philipp Grotherr, Bastian Fries, Maximilian Faust, Stefanie Steuer, Patrick Swojanowsky, Stephan Willems, Nathaniel Portz, Amar Ujeyl, Matthias Krüger, Robert Gramlich, Till Köhler, Armin Sause, Ina Nover, Athanasios-Panagiotis Ziakos, Veaceslav Ciobanu, Norman Spelsberg, Johannes Siebermair, Amir-Abbas Mahabadi, Miriam Köhler, Nadine Vonderlin, Lisa Riesinger, Edison Abdiu, Anja Bachmann, Marie Frenzel, Astrid Hummel, Kristin Lehnert, Anne Krüger, Franke Busse, Andreas Napp, Dirk Müller-Wieland, Simone Battermann, Philipp Lacour, Tobias Trippel, Nick Lasse Beetz, Leonhard Schleußner, Veronika Zach, Christina Rozados, Harald Mudra, Stephan Staubach, Alexander Illmann, Michael Joner, Matthias Bock, Christof Kolb, Tobias Koch, Rebecca Fröhlich, Carsten Lennerz, Tobias Lenz, Patrick Fuchs, Markus Freißmuth, Christian Grebmer, Jürgen Kuschyk, Malte Kranert, Fabian Fastenrath, Gökhan Yücel, Boris Rudic, Sarah Würfel, Albrecht Römer, Andreas Böhmer, Jörg Honold, Stamatis Georgopoulos, Lukas Gleirscher, Susanne Lederle, Artem Chaplygin, Matthias Pauschinger, Andrea Brinker-Paschke, Jana Kropacek, Lars Eckardt, Christian Ellermann, Niklas Bode, Florian Reinke, Hauke Engelke, Robert Höllriegel, Felix Woitek, Ephraim Winzer, Karim Ibrahim, Christian Pflücke, Georg Ende, Uwe Speiser, Stephan Haußig, Rolf Wachter, Tobias Uhe, Torsten Konrad, Edgar Zitron, Jeton Destani, Fangyi Fu, Samer Al Said, Ziya Kaya, Wilfried Schgör, and Thomas Senoner

Subjects
Computer applications to medicine. Medical informatics, R858-859.7
Abstract

Summary: Background: Cardiac autonomic dysfunction after myocardial infarction identifies patients at high risk despite only moderately reduced left ventricular ejection fraction. We aimed to show that telemedical monitoring with implantable cardiac monitors in these patients can improve early detection of subclinical but prognostically relevant arrhythmic events. Methods: We did a prospective investigator-initiated, randomised, multicentre, open-label, diagnostic trial at 33 centres in Germany and Austria. Survivors of acute myocardial infarction with left ventricular ejection fraction of 36–50% had biosignal analysis for assessment of cardiac autonomic function. Patients with abnormal periodic repolarisation dynamics (≥5·75 deg2) or abnormal deceleration capacity (≤2·5 ms) were randomly assigned (1:1) to telemedical monitoring with implantable cardiac monitors or conventional follow-up. Primary endpoint was time to detection of serious arrhythmic events defined by atrial fibrillation 6 min or longer, atrioventricular block class IIb or higher and fast non-sustained (>187 beats per min; ≥40 beats) or sustained ventricular tachycardia or fibrillation. This study is registered with ClinicalTrials.gov, NCT02594488. Findings: Between May 12, 2016, and July 20, 2020, 1305 individuals were screened and 400 patients at high risk were randomly assigned (median age 64 years [IQR 57–73]); left ventricular ejection fraction 45% [40–48]) to telemedical monitoring with implantable cardiac monitors (implantable cardiac monitor group; n=201) or conventional follow-up (control group; n=199). During median follow-up of 21 months, serious arrhythmic events were detected in 60 (30%) patients of the implantable cardiac monitor group and 12 (6%) patients of the control group (hazard ratio 6·33 [IQR 3·40–11·78]; p

Published
2022
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3. MOVING: Motivation-Oriented interVention study for the elderly IN Greifswald: study protocol for a randomized controlled trial

Author

Fabian Kleinke, Thea Schwaneberg, Franziska Weymar, Peter Penndorf, Sabina Ulbricht, Kristin Lehnert, Marcus Dörr, Wolfgang Hoffmann, and Neeltje van den Berg

Subjects
Physical activity, Sedentary behavior, Accelerometry, Elderly individuals (people), motivation, Behavior change, Medicine (General), R5-920
Abstract

Abstract Background Cardiovascular diseases (CVD) are the leading cause of mortality. In 2014, they were responsible for 38.9% of all causes of death in Germany. One major risk factor for CVD is a lack of physical activity (PA). A health-promoting lifestyle including regular PA and minimizing sitting time (ST) in daily life is a central preventive measure. Previous studies have shown that PA decreases in older age; 2.4–29% of the people aged over 60 years achieve the World Health Organization recommendations. This age group spends on average 9.4 h per day in sedentary activities. To increase PA and decrease ST, a low-threshold intervention, consisting of individualized feedback letters based on objectively measured data of PA and ST, was developed. The research question is: Do individual feedback letters, based on accelerometer data, have a positive effect on PA and ST? Methods/design MOVING is a two-arm, randomized controlled trial. Inclusion criteria are age ≥ 65 years and the ability to be physically active. Exclusion criteria are the permanent use of a wheelchair and simultaneous participation in another study on PA. At baseline participants who give informed consent will receive general information and recommendations about the positive effects of regular PA and less ST. Participants of both groups will receive an accelerometer device, which records PA and ST over a period of seven consecutive days following by a randomization. Participants in the intervention group will receive automatically generated, individualized feedback letters by mail based on their PA and ST at baseline and at 3-month follow-up. Further follow-up examinations will be carried out at 6 and 12 months. The primary outcome is the increase of PA and the reduction of ST after 6 months in the intervention group compared to the control group. Discussion The goal of the study is to examine the effects of a simple feedback intervention on PA and ST in elderly people. We aim to achieve an effect of 20% increase in moderate-to-vigorous physical activity (MVPA). The intervention may have the potential to decrease crucial cardiovascular risk factors and, therefore, contribute to prevention of CVD. Trial registration German Clinical Trials Register, ID: DRKS00010410 . Registered on 17 May 2017.

Published
2018
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5. High-Mobility Group Box Protein 1 Is an Independent Prognostic Marker for All-Cause Mortality in Patients With Dilated Cardiomyopathy

Author

Andreas Kümmel, Stefan Gross, Rico Feldtmann, Bishwas Chamling, Anne Strohbach, Kristin Lehnert, Martin Bahls, Lisa Loerzer, Katharina Moormann, Jeannine Witte, Alexander Riad, Marcus Dörr, Jens Fielitz, and Stephan B. Felix

Subjects
Cardiomyopathy, Dilated, Natriuretic Peptide, Brain, Humans, Female, HMGB1 Protein, Middle Aged, Prognosis, Cardiology and Cardiovascular Medicine, Biomarkers, Peptide Fragments, Proportional Hazards Models
Abstract

High-mobility group box protein 1 (HMGB1) is released during tissue damage and activates the innate immune system through toll-like receptor 4. Because mortality in dilated cardiomyopathy (DCM) is associated with activation of the innate immune system, we hypothesized that HMGB1 possesses a prognostic value in estimating mortality in patients with DCM. We determined HMGB1 and N-terminal B-type natriuretic peptide (NT-proBNP) levels in 67 patients with DCM (12 women, mean age 53.6 ± 1.5 years). Kaplan-Meier analyzes revealed that higher levels of HMGB1 and NT-proBNP are related to increased all-cause mortality. Multivariable Cox regression confirmed HMGB1 as a risk factor for mortality in patients with DCM, independent of NT-proBNP, age, and gender (hazard ratio per 1 SD 1.920, 95% confidence interval 1.401 to 2.631, plt;0.001). HMGB1 is a promising candidate to estimate the prognosis of patients with DCM.

Published
2022

6. The DZHK research platform: maximisation of scientific value by enabling access to health data and biological samples collected in cardiovascular clinical studies

Author

Julia Hoffmann, Sabine Hanß, Monika Kraus, Jens Schaller, Christian Schäfer, Dana Stahl, Stefan D. Anker, Gabriele Anton, Thomas Bahls, Stefan Blankenberg, Arne Blumentritt, Leif-Hendrik Boldt, Steffen Cordes, Steffen Desch, Wolfram Doehner, Marcus Dörr, Frank Edelmann, Ingo Eitel, Matthias Endres, Stefan Engelhardt, Jeanette Erdmann, Katharina Eulenburg, Volkmar Falk, Stephan B. Felix, Derk Frank, Thomas Franke, Norbert Frey, Tim Friede, Lars Geidel, Lisa Germans, Ulrich Grabmaier, Martin Halle, Jörg Hausleiter, Vera Jakobi, Ahmad-Fawad Jebran, Alexander Jobs, Stefan Kääb, Mahir Karakas, Hugo A. Katus, Alexandra Klatt, Christoph Knosalla, Joachim Krebser, Ulf Landmesser, Mahsa Lee, Kristin Lehnert, Stephanie Lesser, Katrin Leyh, Roberto Lorbeer, Stephanie Mach-Kolb, Benjamin Meder, Eike Nagel, Christian H. Nolte, Abdul S. Parwani, Astrid Petersmann, Miriam Puls, Henriette Rau, Maximilian Reiser, Otto Rienhoff, Tabea Scharfe, Mario Schattschneider, Heiko Scheel, Renate B. Schnabel, Andreas Schuster, Boris Schmitt, Tim Seidler, Moritz Seiffert, Barbara-Elisabeth Stähli, Adriane Stas, Thomas J. Stocker, Lukas von Stülpnagel, Holger Thiele, Rolf Wachter, Reza Wakili, Tanja Weis, Kerstin Weitmann, Heinz-Erich Wichmann, Philipp Wild, Tanja Zeller, Wolfgang Hoffmann, Elisabeth Maria Zeisberg, Wolfram-Hubertus Zimmermann, Dagmar Krefting, Titus Kühne, Annette Peters, Gerd Hasenfuß, Steffen Massberg, Thomas Sommer, Stefanie Dimmeler, Thomas Eschenhagen, and Matthias Nauck

Subjects
Cancer Research, Data and biomaterial collection, Research platform, ddc:610, Standardisation, General Medicine, Cardiovascular disease, Cardiology and Cardiovascular Medicine, German Centre for Cardiovascular Research
Abstract

The German Centre for Cardiovascular Research (DZHK) is one of the German Centres for Health Research and aims to conduct early and guideline-relevant studies to develop new therapies and diagnostics that impact the lives of people with cardiovascular disease. Therefore, DZHK members designed a collaboratively organised and integrated research platform connecting all sites and partners. The overarching objectives of the research platform are the standardisation of prospective data and biological sample collections among all studies and the development of a sustainable centrally standardised storage in compliance with general legal regulations and the FAIR principles. The main elements of the DZHK infrastructure are web-based and central units for data management, LIMS, IDMS, and transfer office, embedded in a framework consisting of the DZHK Use and Access Policy, and the Ethics and Data Protection Concept. This framework is characterised by a modular design allowing a high standardisation across all studies. For studies that require even tighter criteria additional quality levels are defined. In addition, the Public Open Data strategy is an important focus of DZHK. The DZHK operates as one legal entity holding all rights of data and biological sample usage, according to the DZHK Use and Access Policy. All DZHK studies collect a basic set of data and biosamples, accompanied by specific clinical and imaging data and biobanking. The DZHK infrastructure was constructed by scientists with the focus on the needs of scientists conducting clinical studies. Through this, the DZHK enables the interdisciplinary and multiple use of data and biological samples by scientists inside and outside the DZHK. So far, 27 DZHK studies recruited well over 11,200 participants suffering from major cardiovascular disorders such as myocardial infarction or heart failure. Currently, data and samples of five DZHK studies of the DZHK Heart Bank can be applied for.

Published
2023

7. Longitudinal Clinical Features of Post-COVID-19 Patients—Symptoms, Fatigue and Physical Function at 3- and 6-Month Follow-Up

Author

Dörr, Anke Steinmetz, Stefan Gross, Kristin Lehnert, Petra Lücker, Nele Friedrich, Matthias Nauck, Susanne Bahlmann, Jens Fielitz, and Marcus

Subjects
post-COVID-19-syndrome, long COVID, rehabilitation, physical function, fatigue, psychological profile, 6-min-walk-test, cognitive function, laboratory parameters
Abstract

Post-COVID-19 syndrome (PCS) has been described as ‘the pandemic after the pandemic’ with more than 65 million people worldwide being affected. The enormous range of symptoms makes both diagnosis complex and treatment difficult. In a post-COVID rehabilitation outpatient clinic, 184 patients, mostly non-hospitalized, received a comprehensive, interdisciplinary diagnostic assessment with fixed follow-up appointments. At baseline, three in four patients reported more than 10 symptoms, the most frequent symptoms were fatigue (84.9%), decreased physical capacity (83.0%), tiredness (81.1%), poor concentration (73.6%), sleeping problems (66.7%) and shortness of breath (67.3%). Abnormalities were found in the mean values of scores for fatigue (FAS = 34.3), cognition (MoCA = 25.5), psychological alterations (anxiety, depression, post-traumatic stress disorder), limitation of lung function (CAT) and severity scores for PCS (PCFS, MCRS). Clinical abnormalities were found in elevated values of heart rate, breathing rate at rest, blood pressure and NT-proBNP levels. As the frequency of the described symptoms decreases only slowly but most often significantly over the course, it is important to monitor the patients over a longer period of time. Many of them suffer from an immense symptom burden, often without pre-existing clinical correlates. Our results show a clear association with objectifiable assessments and tests as well as pronounced symptoms.

Published
2023
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8. Myeloid differentiation factor‐2 activates monocytes in patients with dilated cardiomyopathy

Author

Rico Feldtmann, Andreas Kümmel, Bishwas Chamling, Anne Strohbach, Kristin Lehnert, Stefan Gross, Lisa Loerzer, Alexander Riad, Diana Lindner, Dirk Westermann, Jens Fielitz, Marcus Dörr, and Stephan B. Felix

Subjects
Cardiomyopathy, Dilated, Inflammation, Lipopolysaccharides, Immunology, Lymphocyte Antigen 96, NF-kappa B, Endothelial Cells, Monocytes, Toll-Like Receptor 4, Mice, Myeloid Differentiation Factor 88, Animals, Humans, Immunology and Allergy
Abstract

Plasma levels of myeloid differentiation factor-2 (MD-2), a co-receptor of toll-like-receptor 4 (TLR4), independently predict mortality in patients with dilated cardiomyopathy (DCM). We tested whether monocyte activation by MD-2 contributes to immune activation and inflammatory status in DCM patients. We found increased MD-2 plasma levels in 25 patients with recent-onset DCM (1250 ± 80.7 ng/ml) compared to 25 age- and gender-matched healthy controls (793.4 ± 52.0 ng/ml; p 0.001). Monocytes isolated from DCM patients showed a higher expression (141.7 ± 12.4%; p = 0.006 vs. controls) of the MD-2 encoding gene, LY96 and an increased NF-κB-activation. Further, the TLR4-activator lipopolysaccharide (LPS) caused a higher increase in interleukin (IL)-6 in monocytes from DCM patients compared to controls (mean fluorescence intensity: 938.7 ± 151.0 vs. 466.9 ± 51.1; p = 0.005). MD-2 increased IL-6 secretion in a TLR4/NF-κB-dependent manner in monocyte-like THP-1-cells as demonstrated by TLR4-siRNA and NF-κB-inhibition. Since endothelial cells (ECs) are responsible for recruiting monocytes to the site of inflammation, ECs were treated with MD-2 leading to an activation of Akt and increased secretion of monocyte-chemoattractant-protein-1 (MCP-1). Activation of ECs by MD-2 was accompanied by an increased expression of the adhesion molecules CD54, CD106 and CD62E, resulting in an increased monocyte recruitment, which was attenuated by CD54 inhibition. In addition, in murine WT but not LY96-KO bone marrow-derived macrophages LPS increased the amount of CD54 and CD49d/CD29. MD-2 facilitates a pro-inflammatory status of monocytes and EC-mediated monocyte recruitment via TLR4/NF-κB. Elevated MD-2 plasma levels are possibly involved in monocyte-related inflammation-promoting disease progression in DCM. Our results suggest that MD-2 contributes to increasing monocytic inflammatory activity and triggers the recruitment of monocytes to ECs in DCM.

Published
2022

9. The Greifswald Post COVID Rehabilitation Study and Research (PoCoRe)-Study Design, Characteristics and Evaluation Tools

Author

Anke Steinmetz, Susanne Bahlmann, Corinna Bergelt, Barbara M. Bröker, Ralf Ewert, Stephan B. Felix, Agnes Flöel, Robert Fleischmann, Wolfgang Hoffmann, Silva Holtfreter, Matthias Nauck, Katja Riemann, Christian Scheer, Dana Stahl, Antje Vogelgesang, Uwe Völker, Ulrich Wiesmann, Johanna Klinger-König, René Walk, Hans J. Grabe, Stefan Gross, Kristin Lehnert, Jens Fielitz, and Marcus Dörr

Subjects
cardiopulmonary function, biobanking, non-hospitalized patients, psychological profile, post-COVID syndrome, 6-min-walk-test, after-care, General Medicine, ddc:610, cognitive function, rehabilitation
Abstract

(1) Background: COVID-19 is often associated with significant long-term symptoms and disability, i.e., the long/post-COVID syndrome (PCS). Even after presumably mild COVID-19 infections, an increasing number of patients seek medical help for these long-term sequelae, which can affect various organ systems. The pathogenesis of PCS is not yet understood. Therapy has so far been limited to symptomatic treatment. The Greifswald Post COVID Rehabilitation Study (PoCoRe) aims to follow and deeply phenotype outpatients with PCS in the long term, taking a holistic and comprehensive approach to the analysis of their symptoms, signs and biomarkers. (2) Methods: Post-COVID outpatients are screened for symptoms in different organ systems with a standardized medical history, clinical examination, various questionnaires as well as physical and cardiopulmonary function tests. In addition, biomaterials are collected for the analysis of immunomodulators, cytokines, chemokines, proteome patterns as well as specific (auto)antibodies. Patients are treated according to their individual needs, adhering to the current standard of care. PoCoRe’s overall aim is to optimize diagnostics and therapy in PCS patients.

Published
2023

10. Contemporary Management of Severe Symptomatic Aortic Stenosis

Author

Marc Eugène, Piotr Duchnowski, Bernard Prendergast, Olaf Wendler, Cécile Laroche, Jean-Luc Monin, Yannick Jobic, Bogdan A. Popescu, Jeroen J. Bax, Alec Vahanian, Bernard Iung, Jeroen Bax, Michele De Bonis, Victoria Delgado, Michael Haude, Gerhard Hindricks, Aldo P. Maggioni, Luc Pierard, Susanna Price, Raphael Rosenhek, Frank Ruschitzka, Stephan Windecker, Souad Mekhaldi, Katell Lemaitre, Sébastien Authier, Magdy Abdelhamid, Astrid Apor, Gani Bajraktari, Branko Beleslin, Alexander Bogachev-Prokophiev, Daniela Cassar Demarco, Agnes Pasquet, Sait Mesut Dogan, Andrejs Erglis, Arturo Evangelista, Artan Goda, Nikolaj Ihlemann, Huseyin Ince, Andreas Katsaros, Katerina Linhartova, Julia Mascherbauer, Erkin Mirrakhimov, Vaida Mizariene, Shelley Rahman-Haley, Regina Ribeiras, Fuad Samadov, Antti Saraste, Iveta Simkova, Elizabeta Srbinovska Kostovska, Lidia Tomkiewicz-Pajak, Christophe Tribouilloy, Eliverta Zera, Mimoza Metalla, Ervina Shirka, Elona Dado, Loreta Bica, Jorida Aleksi, Gerti Knuti, Lidra Gjyli, Rudina Pjeci, Eritinka Shuperka, Erviola Lleshi, Joana Rustemaj, Marsjon Qordja, Mirald Gina, Senada Husi, Daniel Basic, Regina Steringer-Mascherbauer, Charlotte Huber, Christian Ebner, Elisabeth Sigmund, Andrea Ploechl, Thomas Sturmberger, Veronica Eder, Tanja Koppler, Maria Heger, Andreas Kammerlander, Franz Duca, Christina Binder, Matthias Koschutnik, Leonard Perschy, Lisa Puskas, Chen-Yu Ho, Farid Aliyev, Vugar Guluzada, Galib Imanov, Firdovsi Ibrahimov, Abbasali Abbasaliyev, Tahir Ahmedov, Fargana Muslumova, Jamil Babayev, Yasmin Rustamova, Tofig Jahangirov, Rauf Samadov, Muxtar Museyibov, Elnur Isayev, Oktay Musayev, Shahin Xalilov, Saleh Huseynov, Madina Yuzbashova, Vuqar Zamanov, Vusal Mammadov, Gery Van Camp, Martin Penicka, Hedwig Batjoens, Philippe Debonnaire, Daniel Dendooven, Sebastien Knecht, Mattias Duytschaever, Yves Vandekerckhove, Luc Missault, Luc Muyldermans, René Tavernier, Tineke De Grande, Patrick Coussement, Joyce DeTroyer, Katrien Derycker, Kelly De Jaegher, Antoine Bondue, Christophe Beauloye, Céline Goffinet, Daniela Corina Mirica, Frédéric Vanden Eynden, Philippe Van de Borne, Béatrice Van Frachen, David Vancraeynest, Jean Louis Vanoverschelde, Sophie Pierard, Mihaela Malanca, Florence Sinnaeve, Séverine Tahon, Marie De Clippel, Frederic Gayet, Jacques Loiseau, Nico Van de Veire, Veronique Moerman, Anne-Marie Willems, Bernard Cosyns, Steven Droogmans, Andreea Motoc, Dirk Kerkhove, Daniele Plein, Bram Roosens, Caroline Weytjens, Patrizio Lancellotti, Elena Raluca Dulgheru, Ilona Parenicova, Helena Bedanova, Frantisek Tousek, Stepanka Sindelarova, Julia Canadyova, Milos Taborsky, Jiri Ostransky, null Ivona simkova, Marek Vicha, Libor Jelinek, Irena Opavska, Miroslav Homza, Miriam Kvrayola, Radim Brat, Dan Mrozek, Eva Lichnerova, Iveta Docekalova, Marta Zarybnicka, Marketa Peskova, Patrik Roucka, Vlasta Stastna, Dagmar Jungwirtova Vondrackova, Alfred Hornig, Matus Niznansky, Marian Branny, Alexandra Vodzinska, Miloslav Dorda, Libor Snkouril, Krystyna Kluz, Jana Kypusova, Radka Nezvalova, Niels Thue Olsen, Hosam Hasan Ali, Salma Taha, Mohamed Hassan, Ahmed Afifi, Hamza Kabil, Amr Mady, Hany Ebaid, Yasser Ahmed, Mohammad Nour, Islam Talaat, CairoMaiy El Sayed, Ahmad Elsayed Mostafa, CairoYasser Sadek, CairoSherif Eltobgi, Sameh Bakhoum, Ramy Doss, Mahmoud Sheashea, Abd Allah Elasry, Ahmed Fouad, Mahmoud Baraka, Sameh Samir, Alaa Roshdy, Yasmin AbdelRazek, Mostafa M. Abd Rabou, Ahmed Abobakr, Moemen Moaaz, Mohamed Mokhtar, Mohamed Ashry, Khaled Elkhashab, Haytham Soliman Ghareeb, Mostafa Kamal, Gomaa AbdelRazek, GizaNabil Farag, Giza:Ahmed Elbarbary, Evette Wahib, Ghada Kazamel, Diaa Kamal, Mahmoud Tantawy, Adel Alansary, Mohammed Yahia, Raouf Mahmoud, Tamer El Banna, Mohamed Atef, Gamela Nasr, Salah Ahmed, Ehab E. El Hefny, Islam Saifelyazal, Mostafa Abd El Ghany, Abd El Rahman El Hadary, Ahmed Khairy, Jyri Lommi, Mika Laine, Minna Kylmala, Katja Kankanen, Anu Turpeinen, Juha Hartikainen, Lari Kujanen, Juhani Airaksinen, Tuija Vasankari, Catherine Szymanski, Yohann Bohbot, Mesut Gun, Justine Rousseaux, Loic Biere, Victor Mateus, Martin Audonnet, Jérémy Rautureau, Charles Cornet, Emmanuel Sorbets, BourgesKarine Mear, Adi Issa, Florent Le Ven, Marie-Claire Pouliquen, Martine Gilard, Alice Ohanessian, Ali Farhat, Alina Vlase, Fkhar Said, Caroline Lasgi, Carlos Sanchez, Romain Breil, Marc Peignon, Jean-Philippe Elkaim, Virginie Jan-Blin, Sylvain Ropars BertrandM'Ban, Hélène Bardet, Samuel Sawadogo, Aurélie Muschoot, Dieudonné Tchatchoua, Simon Elhadad, Aline Maubert, Tahar Lazizi, Kais Ourghi, Philippe Bonnet, Clarisse Menager-Gangloff, Sofiene Gafsi, Djidjiga Mansouri, Victor Aboyans, Julien Magne, Elie Martins, Sarah Karm, Dania Mohty, Guillaume Briday, Amandine David, Sylvestre Marechaux, Caroline Le Goffic, Camille Binda, Aymeric Menet, Francois Delelis, Anne Ringlé, Anne-Laure Castel, Ludovic Appert, Domitille Tristram, Camille Trouillet, Yasmine Nacer, Lucas Ngoy, MarseilleGilbert Habib, Franck Thuny, Julie Haentjens, Jennifer Cautela, Cécile Lavoute, Floriane Robin, Pauline Armangau, Ugo Vergeylen, Khalil Sanhadji, Nessim Hamed Abdallah, Hassan Kerzazi, Mariana Perianu, François Plurien, Chaker Oueslati, Mathieu Debauchez, Zannis Konstantinos, Alain Berrebi, Alain Dibie, Emmanuel Lansac, Aurélie Veugeois, Christelle Diakov, Christophe Caussin, Daniel Czitrom, Suzanna Salvi, Nicolas Amabile, Patrice Dervanian, Stéphanie Lejeune, Imane Bagdadi, Yemmi Mokrane, Gilles Rouault, Jerome Abalea, Marion Leledy, Patrice Horen, Erwan Donal, Christian Bosseau, Elise Paven, Elena Galli, Edouard Collette, Jean-Marie Urien, Valentin Bridonneau, Renaud Gervais, Fabrice Bauer, Houzefa Chopra, Arthur Charbonnier, David Attias, Nesrine Dahouathi, Moukda Khounlaboud, Magalie Daudin, Christophe Thebault, Cécile Hamon, Philippe Couffon, Catherine Bellot, Maelle Vomscheid, Anne Bernard, Fanny Dion, Djedjiga Naudin, Mohammed Mouzouri, Mathilde Rudelin, Alain Berenfeld, Thibault Vanzwaelmen, Tarik Alloui, Marija Gjerakaroska Radovikj, Slavica Jordanova, Werner Scholtz, Eva Liberda-Knoke, Melanie Wiemer, Andreas Mugge, Georg Nickenig, Jan-Malte Sinning, Alexander Sedaghat, Matthias Heintzen, Jan Ballof, Daniel Frenk, Rainer Hambrecht, Harm Wienbergen, Annemarie Seidel, Rico Osteresch, Kirsten Kramer, Janna Ziemann, Ramona Schulze, Wolfgang Fehske, Clarissa Eifler, Bahram Wafaisade, Andreas Kuhn, Sören Fischer, Lutz Lichtenberg, Mareike Brunold, Judith Simons, Doris Balling, Thomas Buck, Bjoern Plicht, Wolfgang Schols, Henning Ebelt, Marwan Chamieh, Jelena Anacker, Tienush Rassaf, Alexander Janosi, Alexander Lind, Julia Lortz, Peter Lüdike, Philipp Kahlert, Harald Rittger, Gabriele Eichinger, Britta Kuhls, Stephan B. Felix, Kristin Lehnert, Ann-Louise Pedersen, Marcus Dorr, Klaus Empen, Sabine Kaczmarek, Mathias Busch, Mohammed Baly, Fikret Er, Erkan Duman, Linda Gabriel, Christof Weinbrenner, Johann Bauersachs, Julian Wider, Tibor Kempf, Michael Bohm, Paul-Christian Schulze, C. Tudor Poerner, Sven Möbius-Winkler, Karsten Lenk, Kerstin Heitkamp, Marcus Franz, Sabine Krauspe, Burghard Schumacher, Volker Windmuller, Sarah Kurwitz, Holger Thiele, Thomas Kurz, Roza Meyer-Saraei, Ibrahim Akin, Christian Fastner, Dirk Lossnitzer, Ursula Hoffmann, Martin Borggrefe, Stefan Baumann, Brigitte Kircher, Claudia Foellinger, Heike Dietz, Bernhard Schieffer, Feraydoon Niroomand, Harald Mudra, Lars Maier, Daniele Camboni, Christoph Birner, Kurt Debl, Michael Paulus, Benedikt Seither, Nour Eddine El Mokhtari, Alper Oner, Evren Caglayan, Mohammed Sherif, Seyrani Yucel, Florian Custodis, Robert Schwinger, Marc Vorpahl, Melchior Seyfarth, Ina Nover, Till Koehler, Sarah Christiani, David Calvo Sanchez, Barbel Schanze, Holger Sigusch, Athir Salman, Jane Hancock, John Chambers, Camelia Demetrescue, Claire Prendergast, Miles Dalby, Robert Smith, Paula Rogers, Cheryl Riley, Dimitris Tousoulis, Ioannis Kanakakis, Konstantinos Spargias, Konstantinos Lampropoulos, Tolis Panagiotis, Athanasios Koutsoukis, Lampros Michalis, Ioannis Goudevenos, Vasileios Bellos, Michail Papafaklis, Lampros Lakkas, George Hahalis, Athanasios Makris, Haralampos Karvounis, Vasileios Kamperidis, Vlasis Ninios, Vasileios Sachpekidis, Pavlos Rouskas, Leonidas Poulimenos, Georgios Charalampidis, Eftihia Hamodraka, Athanasios Manolis, Robert Gabor Kiss, Tunde Borsanyi, Zoltan Jarai, Andras Zsary, Elektra Bartha, Annamaria Kosztin, Alexandra Doronina, Attila Kovacs, Barabas Janos Imre, Chun Chao, Kalman Benke, Istvan Karoczkai, Kati Keltai, Zsolt Förchécz, Zoltán Pozsonyi, Zsigmond Jenei, Adam Patthy, Laszlo Sallai, Zsuzsanna Majoros, Tamás Pál, Jusztina Bencze, Ildiko Sagi, Andrea Molnar, Anita Kurczina, Gabor Kolodzey, Istvan Edes, Valeria Szatmari, Zsuzsanna Zajacz, Attila Cziraki, Adam Nemeth, Reka Faludi, Laszlone Vegh, Eva Jebelovszki, Geza Karoly Lupkovics, Zsofia Kovacs, Andras Horvath, Gezim Berisha, Pranvera Ibrahimi, Luan Percuku, Rano Arapova, Elmira Laahunova, Kseniia Neronova, Zarema Zhakypova, Gulira Naizabekova, Gulnazik Muratova, Iveta Sime, Nikolajs Sorokins, Ginta Kamzola, Irina Cgojeva-Sproge, Gita Rancane, Ramune Valentinaviciene, Laima Rudiene, Rasa Raugaliene, Aiste Bardzilauske, Regina Jonkaitiene, Jurate Petrauskaite, Monika Bieseviciene, Raimonda Verseckaite, Ruta Zvirblyte, Danute Kalibatiene, Greta Radauskaite, Gabija Janaviciute-Matuzeviciene, Dovile Jancauskaite, Deimile Balkute, Juste Maneikyte, Ingrida Mileryte, Monika Vaisvilaite, Lina Gedvilaite, Mykolas Biliukas, Vaiva Karpaviciene, Robert George Xuereb, Elton Pllaha, Roxana Djaberi, Klaudiusz Komor, Agnieszka Gorgon-Komor, Beata Loranc, Jaroslaw Myszor, Katarzyna Mizia-Stec, Adrianna Berger-Kucza, Magdalena Mizia, Mateusz Polak, Piotr Bogacki, Piotr Podolec, Monika Komar, Ewa Sedziwy, Dorota Sliwiak, Bartosz Sobien, Beata Rog, Marta Hlawaty, Urszula Gancarczyk, Natasza Libiszewska, Danuta Sorysz, Andrzej Gackowski, Malgorzata Cieply, Agnieszka Misiuda, Franciszek Racibor, Anna Nytko, Kazimierz Widenka, Maciej Kolowca, Janusz Bak, Andrzej Curzytek, Mateusz Regulski, Malgorzata Kamela, Mateusz Wisniowski, Tomasz Hryniewiecki, Piotr Szymanski, Monika Rozewicz, Maciej Grabowski, Andrzej Budaj, Beata Zaborska, Ewa Pilichowska-Paskiet, Malgorzata Sikora-Frac, Tomasz Slomski, Isabel Joao, Ines Cruz, Hélder Pereira, Rita Cale, Ana Marques, Ana Rita Pereira, Carlos Morais, Antonio Freitas, David Roque, Nuno Antunes, Antonio Costeira Pereira, Catarina Vieira, Nuno Salome, Juliana Martins, Isabel Campos, Goncalo Cardoso, Claudia Silva, Afonso Oliveira, Mariana Goncalves, Rui Martins, Nuno Quintal, Bruno Mendes, Joseline Silva, Joao Ferreira, James Milner, Patricia Alves, Vera Marinho, Paula Gago, Jose Amado, Joao Bispo, Dina Bento, Inocencia Machado, Margarida Oliveira, Lucy Calvo, Pedro von Hate, Bebiana Faria, Ana Galrinho, Luisa Branco, Antonio Goncalves, Tiago Mendonca, Mafalda Selas, Filipe Macedo, Carla Sousa, Sofia Cabral, Filomena Oliveira, Maria Trepa, Marta Fontes-Oliveira, Alzira Nunes, Paulo Araújo, Vasco Gama Ribeiro, Joao Almeida, Alberto Rodrigues, Pedro Braga, Sonia Dias, Sofia Carvalho, Catarina Ferreira, Alberto Ferreira, Pedro Mateus, Miguel Moz, Silvia Leao, Renato Margato, Ilidio Moreira, Jose Guimanaes, Joana Ribeiro, Fernando Goncalves, Jose Cabral, Ines Almeida, Luisa Goncalves, Mariana Tarusi, Calin Pop, Claudia Matei, Diana Tint, Sanziana Barbulescu, Sorin Micu, Ioana Pop, Costica Baba, Doina Dimulescu, Maria Dorobantu, Carmen Ginghina, Roxana Onut, Andreea Popescu, Brandusa Zamfirescu, Raluca Aflorii, Mihaela Popescu, Liviu Ghilencea, Andreeea Rachieru, Monica Stoian, Nicoleta Oprescu, Silvia Iancovici, Iona Petre, Anca Doina Mateescu, Andreea Calin, Simona Botezatu, Roxana Enache, Monica Rosca, Daniela Ciuperca, Evelyn Babalac, Ruxandra Beyer, Laura Cadis, Raluca Rancea, Raluca Tomoaia, Adela Rosianu, Emese Kovacs, Constantin Militaru, Alina Craciun, Oana Mirea, Mihaela Florescu, Lucica Grigorica, Daniela Dragusin, Luiza Nechita, Mihai Marinescu, Teodor Chiscaneanu, Lucia Botezatu, Costela Corciova, Antoniu Octavian Petris, Catalina Arsenescu-Georgescu, Delia Salaru, Dan Mihai Alexandrescu, Carmjen Plesoianu, Ana Tanasa, Ovidiu Mitu, Irina Iuliana Costache, Ionut Tudorancea, Catalin Usurelu, Gabriela Eminovici, Ioan Manitiu, Oana Stoia, Adriana Mitre, Dan-Octavian Nistor, Anca Maier, Silvia Lupu, Mihaela Opris, Adina Ionac, Irina Popescu, Simina Crisan, Cristian Mornos, Flavia Goanta, Liana Gruescu, Oana Voinescu, Madalina Petcu, Ramona Cozlac, Elena Damrina, Liliya Khilova, Irina Ryazantseva, Dmitry Kozmin, Maria Kiseleva, Marina Goncharova, Kamila Kitalaeva, Victoria Demetskay, Artem Verevetinov, Mikhail Fomenko, Elena Skripkina, Viktor Tsoi, Georgii Antipov, Yuri Schneider, Denis Yazikov, Marina Makarova, Aleksei Cherkes, Natalya Ermakova, Aleksandr Medvedev, Anastasia Sarosek, Mikhail Isayan, Tatyana Voronova, Oleg Kulumbegov, Alina Tuchina, Sergei Stefanov, Margarita Klimova, Konstantin Smolyaninov, Zhargalma Dandarova, Victoriya Magamet, Natalia Spiropulos, Sergey Boldyrev, Kirill Barbukhatty, Dmitrii Buyankov, Vladimir Yurin, Yuriy Gross, Maksim Boronin, Mariya Mikhaleva, Mariya Shablovskaya, Alex Zotov, Daniil Borisov, Vasily Tereshchenko, Ekaterina Zubova, A. Kuzmin, Ivan Tarasenko, Alishir Gamzaev, Natalya Borovkova, Tatyana Koroleva, Svetlana Botova, Ilya Pochinka, Vera Dunaeva, Victoria Teplitskaya, Elena I. Semenova, Olga V. Korabel'Nikova, Denis S. Simonov, Elena Denisenko, Natalia Harina, Natalia Yarohno, Svetlana Alekseeva, Julia Abydenkova, Lyubov Shabalkina, Olga Mayorova, Valeriy Tsechanovich, Igor Medvedev, Michail Lepilin, PenzaEvgenii Nemchenko, Vadim Karnahin, Vasilya Safina, Yaroslav Slastin, Venera Gilfanova, Roman Gorbunov, Ramis Jakubov, Aigul Fazylova, Mansur Poteev, Laysan Vazetdinova, Indira Tarasova, Rishat Irgaliyev, Olga Moiseeva, Mikhail Gordeev, Olga Irtyuga, Raisa Moiseeva, Nina Ostanina, Dmitry Zverev, Patimat Murtazalieva, Dmitry Kuznetsov, Mariya Skurativa, Larisa Polyaeva, Kirill Mihaiilov, Biljana Obrenovic-Kircanski, Svetozar Putnik, Dragan Simic, Milan Petrovic, Natasa Markovic Nikolic, Ljiljana Jovovic, Dimitra Kalimanovska Ostric, Milan Brajovic, Milica Dekleva Manojlovic, Vladimir Novakovic, Danijela Zamaklar-Trifunovic, Bojana Orbovic, Olga Petrovic, Marija Boricic-Kostic, Kristina Andjelkovic, Marko Milanov, Maja Despotovic-Nikolic, Sreten Budisavljevic, Sanja Veljkovic, Nataša Cvetinovic, Daniijela Lepojevic, Aleksandra Todorovic, Aleksandra Nikolic, Branislava Borzanovic, Ljiljana Trkulja, Slobodan Tomic, Milan Vukovic, Jelica Milosavljevic, Mirjana Milanovic, Vladan Stakic, Aleksandra Cvetkovic, Suzana Milutinovic, Olivera Bozic, Miodrag Miladinovic, Zoran Nikolic, Dinka Despotovic, Dimitrije Jovanovic, Anastazija Stojsic-Milosavljevic, Aleksandra Ilic, Mirjana Sladojevic, Stamenko Susak, Srdjan Maletin, Salvo Pavlovic, Vladimir Kuzmanovic, Nikola Ivanovic, Jovana Dejanovic, Dusan Ruzicic, Dragana Drajic, Danijel Cvetanovic, Marija Mirkovic, Jon Omoran, Roman Margoczy, Katarina Sedminova, Adriana Reptova, Eva Baranova, Tatiana Valkovicova, Gabriel Valocik, Marian Kurecko, Marianna Vachalcova, Alzbeta Kollarova, Martin Studencan, Daniel Alusik, Marek Kozlej, Jana Macakova, Sergio Moral, Merce Cladellas, Daniele Luiso, Alicia Calvo, Jordi Palet, Juli Carballo, Gisela Teixido Tura, Giuliana Maldonado, Laura Gutierrez, Teresa Gonzalez-Alujas, Rodriguez Palomares Jose Fernando, Nicolas Villalva, Ma Jose Molina-Mora, Ramon Rubio Paton, Juan Jose Martinez Diaz, Pablo Ramos Ruiz, Alfonso Valle, Ana Rodriguez, Edgardo Alania, Emilio Galcera, Julia Seller, Gonzalo de la Morena Valenzuela, Daniel Saura Espin, Dolores Espinosa Garcia, Maria Jose Oliva Sandoval, Josefa Gonzalez, Miguel Garcia Navarro, Maria Teresa Perez-Martinez, Jose Ramon Ortega Trujillo, Irene Menduina Gallego, Daniel San Roman, Eliu David Perez Nogales, Olga Medina, Rodolfo Antonio Montiel Quintero, Pablo Felipe Bujanda Morun, Marta Lopez Perez, Jimmy Plasencia Huaripata, Juan Jose Morales Gonzalez, Veronica Quevedo Nelson, Jose Luis Zamorano, Ariana Gonzalez Gomez, Alfonso Fraile, Maria Teresa Alberca, Joaquin Alonso Martin, Covadonga Fernandez-Golfin, Javier Ramos, Sergio Hernandez Jimenez, Cristina Mitroi, Pedro L. Sanchez Fernandez, Elena Diaz-Pelaez, Beatriz Garde, Luis Caballero, Fermin Martinez Garcia, Francisco Cambronero, Noelia Castro, Antonio Castro, Alejandro De La Rosa, Pastora Gallego, Irene Mendez, David Villagomez Villegas, Manuel Gonzalez Correa, Roman Calvo, Francisco Florian, Rafael Paya, Esther Esteban, Francisco Buendia, Andrés Cubillos, Carmen Fernandez, Juan Pablo Cárdenas, José Leandro Pérez-Boscá, Joan Vano, Joaquina Belchi, Cristina Iglesia-Carreno, Francisco Calvo Iglesias, Aida Escudero-Gonzalez, Sergio Zapateria-Lucea, Juan Sterling Duarte, Lara Perez-Davila, Rafael Cobas-Paz, Rosario Besada-Montenegro, Maribel Fontao-Romeo, Elena Lopez-Rodriguez, Emilio Paredes-Galan, Berenice Caneiro-Queija, Alba Guitian Gonzalez, Abdi Bozkurt, Serafettin Demir, Durmus Unlu, Caglar Emre Cagliyan, Muslum Firat Ikikardes, Mustafa Tangalay, Osman Kuloglu, Necla Ozer, Ugur Canpolat, Melek Didem Kemaloglu, Abdullah Orhan Demirtas, Didar Elif Akgün, Eyup Avci, Gokay Taylan, Mustafa Adem Yilmaztepe, Fatih Mehmet Ucar, Servet Altay, Muhammet Gurdogan, Naile Eris Gudul, Mujdat Aktas, Mutlu Buyuklu, Husnu Degirmenci, Mehmet Salih Turan, Kadir Ugur Mert, Gurbet Ozge Mert, Muhammet Dural, Sukru Arslan, Nurten Sayar, Batur Kanar, Beste Ozben Sadic, Ahmet Anil Sahin, Ahmet Buyuk, Onur Kilicarslan, Cem Bostan, Tarik Yildirim, Seda Elcim Yildirim, Kahraman Cosansu, Perihan Varim, Ersin Ilguz, Recep Demirbag, Asuman Yesilay, Abdullah Cirit, Eyyup Tusun, Emre Erkus, Muhammet Rasit Sayin, Zeynep Kazaz, Selim Kul, Turgut Karabag, Belma Kalayci, Clinical sciences, Cardio-vascular diseases, and Cardiology

Subjects
Male, medicine.medical_specialty, Multivariate analysis, Clinical Decision-Making, Risk Assessment, Severity of Illness Index, decision making, surgery, Risk Factors, Internal medicine, Intervention (counseling), medicine, Clinical endpoint, Humans, 03.02. Klinikai orvostan, guidelines, Symptomatic aortic stenosis, Aged, Retrospective Studies, Aged, 80 and over, business.industry, valvular heart disease, Disease Management, aortic stenosis, Aortic Valve Stenosis, Odds ratio, medicine.disease, Europe, Stenosis, Treatment Outcome, Echocardiography, Aortic Valve, Charlson comorbidity index, transcatheter aortic valve replacement, Female, Morbidity, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies, surgical aortic valve replacement
Abstract

BACKGROUND There were gaps between guidelines and practice when surgery was the only treatment for aortic stenosis (AS). OBJECTIVES This study analyzed the decision to intervene in patients with severe AS in the EORP VHD (EURObservational Research Programme Valvular Heart Disease) II survey. METHODS Among 2,152 patients with severe AS, 1,271 patients with high-gradient AS who were symptomatic fulfilled a Class I recommendation for intervention according to the 2012 European Society of Cardiology guidelines; the primary end point was the decision for intervention. RESULTS A decision not to intervene was taken in 262 patients (20.6%). In multivariate analysis, the decision not to intervene was associated with older age (odds ratio [OR]: 1.34 per 10-year increase; 95% CI: 1.11 to 1.61; P = 0.002), New York Heart Association functional classes I and II versus III (OR: 1.63; 95% CI: 1.16 to 2.30; P = 0.005), higher age adjusted Charlson comorbidity index (OR: 1.09 per 1-point increase; 95% CI: 1.01 to 1.17; P = 0.03), and a lower transaortic mean gradient (OR: 0.81 per 10-mm Hg decrease; 95% CI: 0.71 to 0.92; P < 0.001). During the study period, 346 patients (40.2%, median age 84 years, median EuroSCORE II [European System for Cardiac Operative Risk Evaluation II] 3.1%) underwent transcatheter intervention and 515 (59.8%, median age 69 years, median EuroSCORE II 1.5%) underwent surgery. A decision not to intervene versus intervention was associated with lower 6-month survival (87.4%; 95% CI: 82.0 to 91.3 vs 94.6%; 95% CI: 92.8 to 95.9; P < 0.001). CONCLUSIONS A decision not to intervene was taken in 1 in 5 patients with severe symptomatic AS despite a Class I recommendation for intervention and the decision was particularly associated with older age and combined comorbidities. Transcatheter intervention was extensively used in octogenarians. (J Am Coll Cardiol 2021;78:2131-2143) (c) 2021 by the American College of Cardiology Foundation.

Published
2021

11. Child–Computer Interaction: From a systematic review towards an integrated understanding of interaction design methods for children

Author

Florence Kristin Lehnert, Antoine Fischbach, Jasmin Niess, Vincent Koenig, Carine Lallemand, Panos Markopoulos, Lehnert, Florence Kristin, Niess, Jasmin, Lallemand, Carine, Markopoulos, Panos, Fischbach, Antoine, and Koenig, Vincent

Subjects
Interaction design methods, Applied psychology, computer science, Mindset, Interaction design, medicine.disease, Triangulation, Multidisciplinaire, généralités & autres [H99] [Sciences sociales & comportementales, psychologie], Preference, Education, Variety (cybernetics), Human-Computer Interaction, Child–Computer Interaction, Children's and adults’ roles, Autism spectrum disorder, medicine, Systematic review, Multidisciplinary, general & others [H99] [Social & behavioral sciences, psychology], Mainstream, other research area, Design methods, Psychology, Children’s and adults’ roles, Qualitative research
Abstract

Child–Computer Interaction (CCI) is a steadily growing field that focuses on children as a prominent and emergent user group. For more than twenty years, the Interaction Design for Children (IDC) community has developed, extended, and advanced research and design methods for children’s involvement in designing and evaluating interactive technologies. However, as the CCI field evolves, the need arises for an integrated understanding of interaction design methods currently applied. To that end, we analyzed 272 full papers across a selection of journals and conference venues from 2005 to 2020. Our review contributes to the literature on this topic by (1) examining a holistic child population, including developmentally diverse children and children from 0 to 18 years old, (2) illustrating the interplay of children’s and adults’ roles across different methods, and (3) identifying patterns of triangulation in the methods applied while taking recent ethical debates about children’s involvement in design into account. While we found that most studies were conducted in natural settings, we observed a preference for evaluating interactive artifacts at a single point in time. Method triangulation was applied in two-thirds of the papers, with a preference for qualitative methods. Researchers used triangulation predominantly with respect to mainstream methods that were not specifically developed for child participants, such as user observation combined with semi-structured interviews or activity logging. However, the CCI field employs a wide variety of creative design methods which engage children more actively in the design process by having them take on roles such as informant and design partner. In turn, we see that more passive children’s roles, e.g., user or tester, are more often linked to an expert mindset by the adult. Adults take on a wider spectrum of roles in the design process when addressing specific developmental groups, such as children with autism spectrum disorder. We conclude with a critical discussion about the constraints involved in conducting CCI research and discuss implications that can inform future methodological advances in the field and underlying challenges.

Published
2021

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