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1. Expert-independent classification of mature B-cell neoplasms using standardized flow cytometry

Author

Leire Burgos, Alberto Orfao, Matthias Ritgen, Vincent H.J. van der Velden, Juan Flores-Montero, Carlos E. Pedreira, Javier Verde, Tomas Kalina, Joana Caetano, Sebastian Böttcher, Georgiana Grigore, Paula Fernandez, Jan Philippé, Rafael Fluxa, Sandra Lange, Robby Engelmann, Michaela Novakova, Quentin Lecrevisse, Jacques J. M. van Dongen, Immunology, European Commission, and European Hematology Association

Subjects
Adult, Pathology, medicine.medical_specialty, Chronic lymphocytic leukemia, Follicular lymphoma, Immunophenotyping, EuroFlow, Medicine and Health Sciences, Medicine, Humans, Hairy cell leukemia, Lymphoma, Follicular, business.industry, Ibrutinib, Univariate, Reproducibility of Results, Biology and Life Sciences, Gold standard (test), Hematology, medicine.disease, Flow Cytometry, Mantle cell lymphoma, Lymphoma, Large B-Cell, Diffuse, Differential diagnosis, business, Rituximab
Abstract

Reproducible expert-independent flow-cytometric criteria for the differential diagnoses between mature B-cell neoplasms are lacking. We developed an algorithm-driven classification for these lymphomas by flow cytometry and compared it to the WHO gold standard diagnosis. Overall, 662 samples from 662 patients representing 9 disease categories were analyzed at 9 laboratories using the previously published EuroFlow 5-tube-8-color B-cell chronic lymphoproliferative disease antibody panel. Expression levels of all 26 markers from the panel were plotted by B-cell entity to construct a univariate, fully standardized diagnostic reference library. For multivariate data analysis, we subsequently used canonical correlation analysis of 176 training cases to project the multidimensional space of all 26 immunophenotypic parameters into 36 2-dimensional plots for each possible pairwise differential diagnosis. Diagnostic boundaries were fitted according to the distribution of the immunophenotypes of a given differential diagnosis. A diagnostic algorithm based on these projections was developed and subsequently validated using 486 independent cases. Negative predictive values exceeding 92.1% were observed for all disease categories except for follicular lymphoma. Particularly high positive predictive values were returned in chronic lymphocytic leukemia (99.1%), hairy cell leukemia (97.2%), follicular lymphoma (97.2%), and mantle cell lymphoma (95.4%). Burkitt and CD10 diffuse large B-cell lymphomas were difficult to distinguish by the algorithm. A similar ambiguity was observed between marginal zone, lymphoplasmacytic, and CD10 diffuse large B-cell lymphomas. The specificity of the approach exceeded 98% for all entities. The univariate immunophenotypic library and the multivariate expert-independent diagnostic algorithm might contribute to increased reproducibility of future diagnostics in mature B-cell neoplasms., This work was supported by the EuroFlow Consortium, which received support from the FP6-2004-LIFESCIHEALTH-5 program of the European Commission (grant LSHB-CT-2006-018708) as Specific Targeted Research Project (STREP). The EuroFlow Consortium is part of the European Scientific Foundation for Hemato-Oncology (ESLHO), a Scientific Working Group (SWG) of the European Hematology Association (EHA).

Published
2022
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2. Cumulative growth and stress responses to the 2018–2019 drought in a European floodplain forest

Author

Rolf A. Engelmann, Christian Wirth, Purrucker S, Florian Schnabel, Carolin Seele-Dilbat, Schmitt L, Ronny Richter, Kahl A, and Georgios Skiadaresis

Subjects
Carbon Isotopes, Drought stress, geography, Global and Planetary Change, Carbon isotope composition, geography.geographical_feature_category, Floodplain, Physiological Stress Responses, Ecology, business.industry, Climate Change, Water supply, Climate change, Forests, Droughts, Forest ecology, Environmental science, Environmental Chemistry, business, Tree species, Ecosystem, General Environmental Science
Abstract

Droughts increasingly threaten the world’s forests and their potential to mitigate climate change. In 2018–2019, Central European forests were hit by two consecutive hotter drought years, an unprecedented phenomenon that is likely to occur more frequently with climate change. Here, we examine tree growth and physiological stress responses (increase in carbon isotope composition; Δδ13C) to this consecutive drought based on tree-rings of dominant tree species in a Central European floodplain forest. Tree growth was not reduced for most species in 2018, indicating that water supply in floodplain forests can partly buffer meteorological water deficits. Drought stress responses in 2018 were comparable to former single drought years but the hotter drought in 2018 induced drought legacies in tree growth while former droughts did not. We observed strong decreases in tree growth and increases in Δδ13C across all tree species in 2019, which are likely driven by the cumulative stress both consecutive hotter droughts exerted. Our results show that consecutive hotter droughts pose a novel threat to forests under climate change, even in forest ecosystems with comparably high levels of water supply.

Published
2021
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3. Automated Design of Robust Genetic Circuits: Structural Variants and Parameter Uncertainty

Author

Christian Hochberger, Nicolai Engelmann, Erik Kubaczka, Heinz Koeppl, and Tobias Schladt

Subjects
genetic design automation, Computer science, robust genetic circuit, circuit synthesis, Biomedical Engineering, Context (language use), cell-to-cell variability, Biochemistry, Genetics and Molecular Biology (miscellaneous), Robustness (computer science), Gene Regulatory Networks, Parametric statistics, Electronic circuit, Gene Library, Combinational logic, business.industry, Uncertainty, structural variants, General Medicine, Automation, Standard algorithms, Electronic design automation, Synthetic Biology, business, Algorithm, Algorithms, Research Article
Abstract

Genetic design automation methods for combinational circuits often rely on standard algorithms from electronic design automation in their circuit synthesis and technology mapping. However, those algorithms are domain-specific and are hence often not directly suitable for the biological context. In this work we identify aspects of those algorithms that require domain-adaptation. We first demonstrate that enumerating structural variants for a given Boolean specification allows us to find better performing circuits and that stochastic gate assignment methods need to be properly adjusted in order to find the best assignment. Second, we present a general circuit scoring scheme that accounts for the limited accuracy of biological device models including the variability across cells and show that circuits selected according to this score exhibit higher robustness with respect to parametric variations. If gate characteristics in a library are just given in terms of intervals, we provide means to efficiently propagate signals through such a circuit and compute corresponding scores. We demonstrate the novel design approach using the Cello gate library and 33 logic functions that were synthesized and implemented in vivo recently (1). We show that an average 1.3-fold and a peak 6.5-fold performance increase can be achieved by simply considering structural variants and that an average 1.8-fold and a peak 30-fold gain in the novel robustness score can be obtained when selecting circuits according to it.Graphical TOC Entry

Published
2021

6. Indikationen und Technik der Frühzystektomie

Author

S. Engelmann, Karl H. Tully, Florian Roghmann, Roman Mayr, Joachim Noldus, and Max Bürger

Subjects
medicine.medical_specialty, Framingham Risk Score, Bladder cancer, business.industry, Urology, General surgery, medicine.medical_treatment, Disease progression, Guideline, medicine.disease, Cystectomy, medicine, Overall survival, business, Very high risk, Selection (genetic algorithm)
Abstract

Early radical cystectomy (RC) is a therapeutic option for non-muscle invasive bladder cancer (NMIBC). The 15-year overall survival after early RC in NMIBC patients is about 70%. Nevertheless, RC is associated with significant morbidity and mortality and therefore requires careful patient selection. The aim of the following review is to assess the selection process for early RC in NMIBC. Especially, the new European Association of Urology (EAU) risk calculator identifying NMIBC patients with very high risk for disease progression is described in detail. Furthermore, the technical aspects of the procedure are evaluated. A review of the current literature (PubMed) and national and international guideline recommendations was also conducted.

Published
2021
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7. Virtual Grocery Store: Fostering Healthy Nutrition among Seniors

Author

Elizabeth Finnerty, Laura Engelmann, Tara L. Crowell, Elizabeth G. Calamidas, and Anthony Dissen

Subjects
Consumption (economics), Program evaluation, Nutrition and Dietetics, Grocery store, business.industry, Baseline data, Consumer Behavior, Purchasing, Food Supply, Community health, Health care, Food desert, Humans, Medicine, Food Assistance, Diet, Healthy, Supermarkets, Geriatrics and Gerontology, Marketing, business
Abstract

AtlantiCare Health System provides health care services to residents in Atlantic City, an urban food desert in southern New Jersey. The purpose of this study is to explore baseline data on the first four months of the program to better understand participants purchasing behaviors. To improve the health of Atlantic City seniors, AltantiCare established a Virtual Grocery Store Program (VGSP). The program covers fees associated with online grocery shopping for 300 residents in Jeffries Towers, a low-income housing complex. Over the course of 4 months, 28 participants placed a total of 151 orders, with a range from 1 to 14 orders each. Out of the 151 orders, that yielded 1,771 items, the top three types of food purchased were fruits and vegetables, dairy and eggs, and meat and fish; one-third of the items were prepared, two-thirds were perishable, and while almost half the items had no nutritional value, out the half that did, the majority had the high nutrition; and less than a third of participants used NJ SNAP funds to purchase their groceries online. Future efforts need to uncover the explanation for these purchases along with identifying potential strategies to increase consumption of healthier food options.

Published
2021
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8. A randomised controlled trial of a family-group cognitive-behavioural (FGCB) preventive intervention for the children of parents with depression: short-term effects on symptoms and possible mechanisms

Author

Alessandra Voggt, Inga Wermuth, Katharina Schmitt, Dana Winogradow, Lina Engelmann, Fabian Loy, Johanna Löchner, Belinda Platt, Mirjam Bley, Kornelija Starman-Wöhrle, Stephanie Hämmerle, Gerd Schulte-Körne, Frans Oort, Esther Neumeier, and Keisuke Takano

Subjects
medicine.medical_specialty, High-risk, RC435-571, CBCL, Pediatrics, RJ1-570, law.invention, Randomized controlled trial, law, Intervention (counseling), Child and adolescent psychiatry, medicine, Family intervention, Depression (differential diagnoses), Parental depression, Psychiatry, business.industry, Cognition, Psychiatry and Mental health, Prevention of depression, Pediatrics, Perinatology and Child Health, Preventive intervention, business, Research Article, Psychopathology, Clinical psychology
Abstract

Objective Parental depression is one of the biggest risk factors for youth depression. This parallel randomized controlled trial evaluates the effectiveness of the German version of the family-group-cognitive-behavioral (FGCB) preventive intervention for children of depressed parents. Methods Families with (i) a parent who has experienced depression and (ii) a healthy child aged 8–17 years (mean = 11.63; 53% female) were randomly allocated (blockwise; stratified by child age and parental depression) to the 12-session intervention (EG; n = 50) or no intervention (CG; usual care; n = 50). Self-reported (unblinded) outcomes were assessed immediately after the intervention (6 months). We hypothesized that CG children would show a greater increase in self-reported symptoms of depression (DIKJ) and internalising/externalising disorder (YSR/CBCL) over time compared to the EG. Intervention effects on secondary outcome variables emotion regulation (FEEL-KJ), attributional style (ASF-KJ), knowledge of depression and parenting style (ESI) were also expected. Study protocol (Belinda Platt, Pietsch, Krick, Oort, & Schulte-Körne, 2014) and trial registration (NCT02115880) reported elsewhere. Results We found significant intervention effects on self-reported internalising ($$\eta_{p}^{2}$$ η p 2 = 0.05) and externalising ($$\eta_{p}^{2}$$ η p 2 = 0.08) symptoms but did not detect depressive symptoms or parent-reported psychopathology. Parental depression severity did not modify these effects. Both groups showed equally improved knowledge of depression ($$\eta_{p}^{2}$$ η p 2 = 0.06). There were no intervention effects on emotion regulation, attributional style or parenting style. Conclusion The German version of the FGCB intervention is effective in reducing symptoms of general psychopathology. There was no evidence that the mechanisms targeted in the intervention changed within the intervention period.

Published
2021

10. Association of circulating PLA2G7 levels with cancer cachexia and assessment of darapladib as a therapy

Author

Mauricio Berriel Diaz, Helmut Friess, Lisa Mehr, Maria Rohm, Michael Voelkl, Julia Zuber, Bernd Engelmann, Inka Zörnig, Søren Fisker Schmidt, Christoph Springfeld, Olga Prokopchuk, Foivos-Filippos Tsokanos, Hanna Kuzi, Pauline Morigny, Doris Kaltenecker, Jeroen Krijgsveld, Victor Laurent, Achim Krüger, Juliano Machado, German Monogarov, Chris D. Hermann, and Stephan Herzig

Subjects
Oncology, medicine.medical_specialty, Cachexia, Inflammation, Diseases of the musculoskeletal system, Mouse models, Systemic inflammation, PLA2G7, Mice, Physiology (medical), Internal medicine, Darapladib, Pancreatic cancer, Oximes, medicine, Animals, Humans, Orthopedics and Sports Medicine, Prospective Studies, Wasting, business.industry, QM1-695, Cancer, Cancer cachexia, Cancer patients, Original Articles, Biomarker, medicine.disease, Pancreatic Neoplasms, RC925-935, Benzaldehydes, Human anatomy, 1-Alkyl-2-acetylglycerophosphocholine Esterase, Cancer Cachexia, Cancer Patients, Mouse Models, Pla2g7, Biomarker (medicine), Original Article, medicine.symptom, business, Biomarkers
Abstract

Background Cancer cachexia (CCx) is a multifactorial wasting disorder characterized by involuntary loss of body weight that affects many cancer patients and implies a poor prognosis, reducing both tolerance to and efficiency of anticancer therapies. Actual challenges in management of CCx remain in the identification of tumour‐derived and host‐derived mediators involved in systemic inflammation and tissue wasting and in the discovery of biomarkers that would allow for an earlier and personalized care of cancer patients. The aim of this study was to identify new markers of CCx across different species and tumour entities. Methods Quantitative secretome analysis was performed to identify specific factors characteristic of cachexia‐inducing cancer cell lines. To establish the subsequently identified phospholipase PLA2G7 as a marker of CCx, plasma PLA2G7 activity and/or protein levels were measured in well‐established mouse models of CCx and in different cohorts of weight‐stable and weight‐losing cancer patients with different tumour entities. Genetic PLA2G7 knock‐down in tumours and pharmacological treatment using the well‐studied PLA2G7 inhibitor darapladib were performed to assess its implication in the pathogenesis of CCx in C26 tumour‐bearing mice. Results High expression and secretion of PLA2G7 were hallmarks of cachexia‐inducing cancer cell lines. Circulating PLA2G7 activity was increased in different mouse models of CCx with various tumour entities and was associated with the severity of body wasting. Circulating PLA2G7 levels gradually rose during cachexia development. Genetic PLA2G7 knock‐down in C26 tumours only partially reduced plasma PLA2G7 levels, suggesting that the host is also an important contributor. Chronic treatment with darapladib was not sufficient to counteract inflammation and tissue wasting despite a strong inhibition of the circulating PLA2G7 activity. Importantly, PLA2G7 levels were also increased in colorectal and pancreatic cancer patients with CCx. Conclusions Overall, our data show that despite no immediate pathogenic role, at least when targeted as a single entity, PLA2G7 is a consistent marker of CCx in both mice and humans. The early increase in circulating PLA2G7 levels in pre‐cachectic mice supports future prospective studies to assess its potential as biomarker for cancer patients.

Published
2021
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11. O Uso do Algoritmo como Instrumento de Construção da Decisão Judicial e a Necessidade de Surpervisão do Uso da Tecnologia no Processo de Tomada de Decisões

Author

Alana Gabriela Engelmann

Subjects
Knowledge management, Work (electrical), Computer science, business.industry, Process (engineering), Judicial opinion, General Medicine, business
Abstract

O presente trabalho tem por objetivo apresentar o uso do algoritmo como instrumento de construção da decisão judicial, quais os benefícios que o uso de referida ferramenta pode trazer para o processo judicial, bem como quais precauções deve-se ter com a utilização da Inteligência Artificial no momento de proferir decisões judiciais. Ainda, se faz uma análise de algumas ferramentas que já se encontram disponíveis para proferir decisões judiciais, demonstrando, assim, que há a necessidade de supervisão do algoritmo utilizado para a prática de atos processuais.

Published
2021
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12. Observed evidence for guideline‐recommended genes in predicting prostate cancer risk from a large population‐based cohort

Author

Wancai Yang, Jianfeng Xu, Jim Lu, Qiang Wang, W. Kyle Resurreccion, Brian T. Helfand, William B. Isaacs, Valentina Engelmann, S. Lilly Zheng, Peter J. Hulick, Kathleen A. Cooney, Lucy Lu, Jun Wei, and Zhuqing Shi

Subjects
Adult, Male, Oncology, medicine.medical_specialty, Urology, Genetic counseling, Population, Risk Assessment, Germline mutation, Internal medicine, Biomarkers, Tumor, Humans, Medicine, Genetic Predisposition to Disease, Genetic Testing, education, CHEK2, Germ-Line Mutation, Aged, Aged, 80 and over, education.field_of_study, business.industry, Prostatic Neoplasms, Odds ratio, Middle Aged, Confidence interval, Cohort, business, Risk assessment
Abstract

BACKGROUND Germline testing for prostate cancer (PCa) is now recommended by the National Comprehensive Cancer Network. While multi-gene testing has been proposed, evidence for their association with PCa risk is not well established. METHODS We tested associations of pathogenic/likely pathogenic mutations in 10 guideline-recommended genes (ATM, BRCA1, BRCA2, CHEK2, PALB2, MLH1, MSH2, MSH6, PMS2, and HOXB13) with PCa risk in the UK Biobank, a population-based cohort. Mutations were annotated based on prostate-specific transcripts using the American College of Medical Genetics and Genomics standards. Associations were tested in 4399 PCa cases and 85,403 unaffected male controls using logistic regression adjusting for age and genetic background. p

Published
2021
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13. Early onset of depression and treatment outcome in patients with major depressive disorder

Author

Marianne B. Müller, Stefanie Wagner, Jan Engelmann, Giulia Treccani, Klaus Lieb, David P. Herzog, André Tadić, Nadine Dreimüller, and Harald Murck

Subjects
medicine.medical_specialty, Treatment outcome, Late onset, Context (language use), 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Humans, Medicine, In patient, Age of Onset, Biological Psychiatry, Depression (differential diagnoses), Early onset, Depressive Disorder, Major, Depression, business.industry, medicine.disease, Antidepressive Agents, 030227 psychiatry, Psychiatry and Mental health, Treatment Outcome, Blood pressure, Major depressive disorder, business, 030217 neurology & neurosurgery
Abstract

Major depressive disorder (MDD) is a highly heterogeneous disorder, which may partly explain why treatment outcome using antidepressants is unsatisfactory. We investigated the onset of depression as a possible clinical marker for therapy response prediction in the context of somatic biomarkers blood pressure and plasma electrolyte concentration. 889 MDD patients were divided into early (EO, n = 226), intermediate (IO, n = 493), and late onset (LO, n = 169) patients and were analyzed for differences in socio-demographic and clinical parameters, comorbidities and treatment outcome as well as systolic blood pressure and electrolytes. EO patients more often suffered from a recurrent depression, had more previous depressive episodes, a higher rate of comorbid axis I and II disorders, and more often reported of suicidality (p 0.001) compared to IO and LO patients. Treatment outcome was not different from IO and LO patients, although LO patients responded faster. EO patients who showed an early non-improvement of depression after 2 weeks of therapy (20% improvement) had a 4.3-fold higher likelihood to become non-remitter as compared to LO patients with an early improvement. EO patients had significantly lower systolic blood pressure than patients with IO or LO and electrolytes in EO patients were significantly correlated with depression severity. Our results confirm other studies showing an association of an early onset of depression with a slower treatment response. The worse treatment outcome in patients with an additional early non-improvement to antidepressant therapy opens perspectives to develop and test individualized treatment approaches for EO and LO patients in the future, which may be based on differences in autonomic regulation.

Published
2021
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14. Reply to: 'G-CSF in acute-on-chronic liver failure – Art of ‘patient selection’ is paramount!'

Author

C Engelmann, Tony Bruns, and Thomas Berg

Subjects
Liver Cirrhosis, medicine.medical_specialty, Cirrhosis, Hepatology, business.industry, Patient Selection, Acute-On-Chronic Liver Failure, medicine.disease, Severity of Illness Index, Gastroenterology, Internal medicine, Granulocyte Colony-Stimulating Factor, Humans, Medicine, Acute on chronic liver failure, business, Selection (genetic algorithm)
Published
2022
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15. How the input shapes the acquisition of verb morphology: elicited production and computational modelling in two highly inflected languages

Author

Julian M. Pine, Marta Szreder, Felix Engelmann, Joanna Kołak, Elena Lieven, Ben Ambridge, Anna L. Theakston, and Sonia Granlund

Subjects
Male, Computer science, computational modelling, computer.software_genre, Verb marking, 0302 clinical medicine, Polish, morphology, Developmental and Educational Psychology, Child, Finland, 05 social sciences, Language acquisition, cross-linguistic, neural networks, Language development, language acquisition, Neuropsychology and Physiological Psychology, Child, Preschool, Female, Suffix, Natural language processing, Child Language, Neural networks, Morphology, Linguistics and Language, Analogy, Verb, Class (philosophy), Experimental and Cognitive Psychology, 050105 experimental psychology, Cross-linguistic, 03 medical and health sciences, Connectionism, Artificial Intelligence, Humans, Learning, 0501 psychology and cognitive sciences, Computer Simulation, Plural, business.industry, elicited production, Finnish, Linguistics, Computational modelling, Elicited production, Artificial intelligence, Neural Networks, Computer, Poland, business, verb marking, computer, 030217 neurology & neurosurgery
Abstract

The aim of the present work was to develop a computational model of howchildren acquire inflectional morphology for marking person and number; oneof the central challenges in language development. First, in order to establishwhich putative learning phenomena are sufficiently robust to constitute a targetfor modelling, we ran large-scale elicited production studies with native learnersof Finnish (N=77; 35-63 months) and Polish (N=81; 35-59 months), using anovel method that, unlike previous studies, allows for elicitation of all six person/number forms in the paradigm (first, second and third person; singularand plural). We then proceeded to build and test a connectionist model of theacquisition of person/number marking which not only acquires near adult-likemastery of the system (including generalisation to unseen items), but also yieldsall of the key phenomena observed in the elicited-production studies; specifically, effects of token frequency and phonological neighbourhood density of the target form, and a pattern whereby errors generally reflect the replacement of low frequency targets by higher-frequency forms of the same verb, or forms with the same person/number as the target, but with a suffix from an inappropriate conjugation class. The findings demonstrate that acquisition of even highly complex systems of inflectional morphology can be accounted for by a theoretical model that assumes rote storage and phonological analogy, as opposed to formal symbolic rules.

Published
2022
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16. Can people detect the trustworthiness of strangers based on their facial appearance?

Author

Bastian Jaeger, Bastiaan Oud, Tony Williams, Eva Krumhuber, Ernst Fehr, Jan Benjamin Engelmann, Faculteit Economie en Bedrijfskunde, Experimental and Political Economics / CREED (ASE, FEB), Department of Social Psychology, Organizational Psychology, and University of Zurich

Subjects
Face perception, FEATURES, INFERENCES, Experimental and Cognitive Psychology, FACES, Trust, computer.software_genre, Arts and Humanities (miscellaneous), 10007 Department of Economics, evolution, TRUTH, ddc:330, SOCIAL ATTRIBUTIONS, Ecology, Evolution, Behavior and Systematics, Accuracy, Trustworthiness, business.industry, JUDGE, behavior and systematics, COVER, 330 Economics, Cooperation, Facial appearance, Artificial intelligence, ecology, Prediction, Psychology, business, computer, BEHAVIOR, Natural language processing
Abstract

Although cooperation can lead to mutually beneficial outcomes, cooperative actions only pay off for the individual if others can be trusted to cooperate as well. Identifying trustworthy interaction partners is therefore a central challenge in human social life. How do people navigate this challenge? Prior work suggests that people rely on facial appearance to judge the trustworthiness of strangers. However, the question of whether these judgments are actually accurate remains debated. The present research examines accuracy in trustworthiness detection from faces and three moderators proposed by previous research. We investigate whether people show above-chance accuracy (a) when they make trust decisions and when they provide explicit trustworthiness ratings, (b) when judging male and female counterparts, and (c) when rating cropped images (with non-facial features removed) and uncropped images. Two studies showed that incentivized trust decisions (Study 1, n = 131 university students) and incentivized trustworthiness predictions (Study 2, n = 266 university students) were unrelated to the actual trustworthiness of counterparts. Accuracy was not moderated by stimulus type (cropped vs. uncropped faces) or counterparts' gender. Overall, these findings suggest that people are unable to detect the trustworthiness of strangers based on their facial appearance, when this is the only information available to them.

Published
2022
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17. Detectability of cannabinoids in the serum samples of cannabis users: Indicators of recent cannabis use? A follow‐up study

Author

Moritz Losacker, Jan Engelmann, Alexandra Philipsen, Nadine Dreimüller, Michael Krämer, Cornelius Hess, Burkhard Madea, Kristina Dücker, and Martin Schäper

Subjects
Time Factors, Cannabigerol, medicine.medical_treatment, Pharmaceutical Science, Physiology, Tetrahydrocannabivarin, 01 natural sciences, Analytical Chemistry, 03 medical and health sciences, chemistry.chemical_compound, Cannabichromene, 0302 clinical medicine, Tandem Mass Spectrometry, medicine, Humans, Environmental Chemistry, 030216 legal & forensic medicine, Spectroscopy, biology, Cannabinoids, business.industry, 010401 analytical chemistry, biology.organism_classification, 0104 chemical sciences, Substance Abuse Detection, chemistry, Tetrahydrocannabinolic acid, Cannabinol, Marijuana Use, Cannabinoid, Sample collection, Cannabis, business, Chromatography, Liquid, Follow-Up Studies, medicine.drug
Abstract

Forensic toxicologists are frequently required to predict the time of last cannabis consumption. Several studies suggested the utility of minor cannabinoids as indicators of recent cannabis use. Because several factors influence blood cannabinoid concentrations, the interpretation of serum cannabinoid concentrations remains challenging. To assess the informative value of serum cannabinoid levels in cannabis users (in total N = 117 patients, including 56 patients who stated an exact time of last cannabis use within 24 h before blood sampling), the detectability of cannabinoids, namely delta-9-tetrahydrocannabinol (delta-9-THC), 11-hydroxy-delta-9-THC, 11-nor-9-carboxy-delta-9-THC, cannabichromene (CBC), cannabidiol (CBD), cannabinol (CBN), cannabidivarin, tetrahydrocannabivarin, cannabigerol (CBG), cannabicyclol, delta-8-THC, tetrahydrocannabinolic acid A, cannabichromenic acid, cannabidiolic acid (CBDA), cannabigerolic acid, cannabicyclolic acid (CBLA), 11-nor-9-carboxy-THCV (THCVCOOH), and 11-nor-CBN-9-COOH, was investigated. Excluding CBDA and CBLA, all investigated cannabinoids were detected in at least one analyzed sample. The interval between cannabis consumption and sample collection (reported by the patients) was not correlated with cannabinoid concentrations. Minor cannabinoids tended to be more easily detected in samples obtained shortly after consumption. However, some samples tested positive for minor cannabinoids despite an interval of several hours or even days between consumption and sampling (according to patients' statements). For instance, CBC, CBG, THCVCOOH, CBD, and CBN in certain cases could be detected more than 24 hours after the last consumption of cannabis. Thus, findings of minor cannabinoids should always be interpreted with caution.

Published
2021
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18. The importance of rectal contrast in CT assessment to detect anastomotic leakage after colorectal surgery

Author

Willem A. Bemelman, C. C. M. Marres, Chistianne J. Buskens, Anthony W. H. van de Ven, Esmee W. M. Engelmann, Hester E. Haak, Graduate School, Surgery, CCA - Cancer Treatment and Quality of Life, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, and CCA - Imaging and biomarkers

Subjects
medicine.medical_specialty, media_common.quotation_subject, laparoscopy, Anastomotic Leak, 030230 surgery, Anastomosis, surgery, 03 medical and health sciences, 0302 clinical medicine, Medicine, Contrast (vision), Humans, In patient, Adverse effect, Laparoscopy, General, media_common, medicine.diagnostic_test, business.industry, Rectal Neoplasms, Primary anastomosis, Anastomosis, Surgical, Gastroenterology, Rectum, Original Articles, Colorectal surgery, radiology, Anastomotic leakage, 030211 gastroenterology & hepatology, Original Article, Radiology, business, Tomography, X-Ray Computed, Colorectal Surgery
Abstract

Aim Computed tomography (CT) is currently the diagnostic tool most often used to detect anastomotic leakage (AL) after colorectal surgery. The aim of this study was to investigate the value of rectal contrast. Method All patients who underwent colorectal surgery with a primary anastomosis between 2009 and 2018 were identified from a prospectively maintained database. Patients who underwent postoperative CT scanning in suspicion of AL were included. The clinical and radiological outcomes of patients with and without rectal contrast were compared. Results A total of 1183 patient records were reviewed; 225 patients underwent CT‐abdomen in suspicion of AL. Of these patients, 175 (77.8%) received rectal contrast. Sensitivity and specificity in this group were 78% and 94%, respectively. The positive predictive value (PPV) was 0.78 and the negative predictive value (NPV) was 0.94. In the group without rectal contrast (n = 50), sensitivity was 47%, specificity 88%, PPV 0.66 and NPV 0.76. In patients who received rectal contrast, contrast reached the anastomosis in 81.7% compared with 26.0% in patients who were given only oral contrast (p

Published
2021

19. Management and Outcome of Hindfoot Trauma With Concomitant Talar Head Injury

Author

Olivier Wijers, Jelle J. Posthuma, Tim Schepers, Esmee W M Engelmann, Graduate School, Surgery, AMS - Musculoskeletal Health, and AMS - Sports

Subjects
medicine.medical_specialty, business.industry, Head injury, Chopart, Articles, talus, medicine.disease, foot fractures, Surgery, Fracture Fixation, Internal, Fractures, Bone, Treatment Outcome, trauma, Concomitant, Quality of Life, medicine, Craniocerebral Trauma, Humans, Head (vessel), Orthopedics and Sports Medicine, business, talonavicular, Retrospective Studies
Abstract

Background: Talar head fractures account for 2.6% to 10% of all talar fractures and are often associated with concomitant musculoskeletal injuries. The current literature only describes a total of 14 patients with talar head fractures and, with that, guidelines for management are lacking. The aim of the current study was to evaluate the management and long-term outcome of patients who have hindfoot trauma with concomitant talar head fractures. Methods: This study includes a retrospective cohort of patients with talar head fractures. Patient characteristics, trauma mechanism, fracture characteristics, treatment, follow-up, and complications were reported. Functional outcome was assessed using the Foot Function Index (FFI) and the American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot score. Quality of life was measured by the EuroQol-5D (EQ-5D). Twenty-one patients with acute fractures of the talar head were identified. The mean follow-up time was 4.9 years. Results: All patients sustained additional ipsilateral foot and/or ankle injuries. Fifteen patients had operative management of their talar head fracture. There were no postoperative wound infections and no cases of avascular necrosis. All fractures united, and 29% of patients developed posttraumatic osteoarthritis. The overall mean FFI score index was 34.2, and the mean AOFAS score was 70.7. The mean EQ-5D index score was 0.74. Conclusion: Talar head fractures always coincided with other (foot) fractures. Management and long-term functional outcome were affected by the extent of associated injuries. Due to the low incidence and high complexity of talar head fractures, early referral to dedicated foot surgeons and centralization of complex foot surgery is recommended. Level of Evidence: Level IV, retrospective case series.

Published
2021
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20. The Current Status of Granulocyte-Colony Stimulating Factor to Treat Acute-on-Chronic Liver Failure

Author

Thierry Thevenot, Thomas Berg, Delphine Weil-Verhoeven, Adam Herber, Annarein J.C. Kerbert, Cornelius Engelmann, Vincent Di Martino, and Niklas Aehling

Subjects
Oncology, medicine.medical_specialty, Hepatology, business.industry, Acute-On-Chronic Liver Failure, medicine.disease, Review article, Granulocyte colony-stimulating factor, End Stage Liver Disease, Clinical trial, Mice, Liver disease, Treatment Outcome, Immune system, Internal medicine, Granulocyte Colony-Stimulating Factor, Animals, Humans, Multicenter Studies as Topic, Medicine, Acute on chronic liver failure, Stem cell, business, Receptor
Abstract

Patients with acute-on-chronic liver failure (ACLF) have a devastating prognosis and therapeutic options are limited. Granulocyte-colony stimulating factor (G-CSF) mobilizes immune and stem cells and possess immune-modulatory and proregenerative capacities. In this review, we aim to define the current evidence for the treatment with G-CSF in end-stage liver disease. Several smaller clinical trials in patients with different severity grades of end-stage liver disease have shown that G-CSF improves survival and reduces the rate of complications. Adequately powered multicenter European trials could not confirm these beneficial effects. In mouse models of ACLF, G-CSF increased the toll-like receptor (TLR)-mediated inflammatory response which led to an increase in mortality. Adding a TLR4 signaling inhibitor allowed G-CSF to unfold its proregenerative properties in these ACLF models. These data suggest that G-CSF requires a noninflammatory environment to exert its protective properties.

Published
2021
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21. IL-6 inhibition with ziltivekimab in patients at high atherosclerotic risk (RESCUE): a double-blind, randomised, placebo-controlled, phase 2 trial

Author

G. Kees Hovingh, Larry Lo, Mads D M Engelmann, Paul M. Ridker, Pablo Pergola, Florian M.M. Baeres, Peter Libby, Rescue Investigators, Milana Ivkovic, Michael H. Davidson, Matt Devalaraja, Dominic S. Raj, Douglas Kling, Experimental Vascular Medicine, Vascular Medicine, and ACS - Atherosclerosis & ischemic syndromes

Subjects
Male, medicine.medical_specialty, Injections, Subcutaneous, Population, Inflammation, Disease, 030204 cardiovascular system & hematology, Antibodies, Monoclonal, Humanized, Placebo, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Internal medicine, medicine, Humans, 030212 general & internal medicine, Renal Insufficiency, Chronic, education, Interleukin 6, Aged, education.field_of_study, biology, Interleukin-6, business.industry, Thrombosis, General Medicine, Middle Aged, Atherosclerosis, medicine.disease, C-Reactive Protein, Treatment Outcome, biology.protein, Biomarker (medicine), Female, medicine.symptom, business, Biomarkers, Kidney disease
Abstract

Background: IL-6 has emerged as a pivotal factor in atherothrombosis. Yet, the safety and efficacy of IL-6 inhibition among individuals at high atherosclerotic risk but without a systemic inflammatory disorder is unknown. We therefore addressed whether ziltivekimab, a fully human monoclonal antibody directed against the IL-6 ligand, safely and effectively reduces biomarkers of inflammation and thrombosis among patients with high cardiovascular risk. We focused on individuals with elevated high-sensitivity CRP and chronic kidney disease, a group with substantial unmet clinical need in whom previous studies in inflammation inhibition have shown efficacy for cardiovascular event reduction. Methods: RESCUE is a randomised, double-blind, phase 2 trial done at 40 clinical sites in the USA. Inclusion criteria were age 18 years or older, moderate to severe chronic kidney disease, and high-sensitivity CRP of at least 2 mg/L. Participants were randomly allocated (1:1:1:1) to subcutaneous administration of placebo or ziltivekimab 7·5 mg, 15 mg, or 30 mg every 4 weeks up to 24 weeks. The primary outcome was percentage change from baseline in high-sensitivity CRP after 12 weeks of treatment with ziltivekimab compared with placebo, with additional biomarker and safety data collected over 24 weeks of treatment. Primary analyses were done in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of assigned treatment. The trial is registered with ClinicalTrials.gov, NCT03926117. Findings: Between June 17, 2019, and Jan 14, 2020, 264 participants were enrolled into the trial, of whom 66 were randomly assigned to each of the four treatment groups. At 12 weeks after randomisation, median high-sensitivity CRP levels were reduced by 77% for the 7·5 mg group, 88% for the 15 mg group, and 92% for the 30 mg group compared with 4% for the placebo group. As such, the median pairwise differences in percentage change in high-sensitivity CRP between the ziltivekimab and placebo groups, after aligning for strata, were –66·2% for the 7·5 mg group, –77·7% for the 15 mg group, and –87·8% for the 30 mg group (all p

Published
2021
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22. High incidence of Epstein–Barr virus, cytomegalovirus, and human-herpes virus-6 reactivations in critically ill patients with COVID-19

Author

L. Robriquet, D. Hober, B. Garcia, A.-S. Moreau, S. Six, A.J. Simonnet, Mercé Jourdain, A. El Kalioubie, and I. Engelmann

Subjects
Adult, Male, Herpesvirus 4, Human, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Critical Illness, Herpesvirus 6, Human, viruses, Epstein -Barr virus, Congenital cytomegalovirus infection, Cytomegalovirus, Viremia, medicine.disease_cause, Article, Virus, law.invention, law, Internal medicine, medicine, Humans, Aged, Retrospective Studies, Coronavirus, Aged, 80 and over, SARS-CoV-2, business.industry, Incidence, virus diseases, Middle Aged, medicine.disease, Intensive care unit, Epstein–Barr virus, Intensive Care Units, Infectious Diseases, Concomitant, Latent Infection, Female, Virus Activation, France, Covid-19, business
Abstract

Background Systemic reactivation of herpesviruses may occur in intensive care unit (ICU) patients and is associated with morbidity and mortality. Data on severe Coronavirus disease-19 (COVID-19) and concomitant reactivation of herpesviruses are lacking. Methods We selected patients admitted to ICU for confirmed COVID-19 who underwent systematic testing for Epstein–Barr virus (EBV), cytomegalovirus (CMV) and human-herpes virus-6 (HHV-6) DNAemia while in the ICU. We retrospectively analysed frequency, timing, duration and co-occurrence of viral DNAemia. Results Thirty-four patients were included. Viremia with EBV, CMV, and HHV-6 was detected in 28 (82%), 5 (15%), and 7 (22%) patients, respectively. EBV reactivation occurred early after ICU admission and was associated with longer ICU length-of-stay. Conclusions While in the ICU, critically ill patients with COVID-19 are prone to develop reactivations due to various types of herpesviruses.

Published
2021
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23. Resistive Memory Process Optimization for High Resistance Switching Toward Scalable Analog Compute Technology for Deep Learning

Author

Steven Consiglio, Qingyun Yang, K. Tapily, Saraf Iqbal Rashid, Muthumanickam Sankarapandian, Paul C. Jamison, Tsunomura Takaaki, C. Catano, Robert D. Clark, T. Ando, R. Pujari, Vijay Narayanan, Hisashi Higuchi, Gerrit J. Leusink, Malte J. Rasch, R. Soave, Hongwen Yan, Ernest Y. Wu, Dexin Kong, Aelan Mosden, Peter Biolsi, Youngseok Kim, Robert R. Robison, O. van der Straten, D. Koty, S. McDermott, Soon-Cheon Seo, Hiroyuki Miyazoe, Son Nguyen, A. Gasasira, Nicole Saulnier, Wilfried Haensch, Sebastian Engelmann, C. S. Wajda, Ramachandran Muralidhar, and S. DeVries

Subjects
010302 applied physics, Physics, business.industry, Deep learning, Process (computing), Topology, 01 natural sciences, Omega, Electronic, Optical and Magnetic Materials, Resistive random-access memory, Stack (abstract data type), 0103 physical sciences, Scalability, Process optimization, Artificial intelligence, Electrical and Electronic Engineering, business, Voltage
Abstract

We demonstrate a novel process for building a Resistive RAM (ReRAM) stack which reduces the forming voltage ( $\text{V}_{\textit {form}}$ ) and increases the switching resistance, both characteristics that are important ingredients for the use of ReRAM in scalable analog compute for AI. Utilizing this process, we explore analog switching characteristics above 100k $\Omega $ and demonstrate 4-bit programming at Rmax $=1\text{M}\Omega $ . Utilizing the same writing characteristics, CIFAR-10 inference simulation shows 90% accuracy, comparable to the full precision model accuracy.

Published
2021
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24. Differences in mortality of cancer patients with COVID-19 in a Brazilian cancer center

Author

Paola Engelmann Arantes, Diego Feriani, Maria Paula Curado, Juliana da Silva Canteras, Gisele Aparecida Fernandes, Ivan Leonardo Avelino França e Silva, Rodrigo Reghini da Silva, and Diego Rodrigues Mendonça e Silva

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Patients, Logistic regression, Article, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Neoplasms, Internal medicine, Case fatality rate, medicine, Humans, Mortality, Risk factor, Survival analysis, Cancer, Retrospective Studies, SARS-CoV-2, business.industry, COVID-19, Hematology, Odds ratio, Middle Aged, Prognosis, medicine.disease, Combined Modality Therapy, Confidence interval, Cancer registry, Survival Rate, Cross-Sectional Studies, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Female, business, Brazil
Abstract

Introduction To analyze COVID-19 mortality in cancer patients and associated factors such as age, sex, type of insurance, situation at COVID-19 diagnosis, and cancer histology during the pandemic at a cancer center in Brazil. Methods Cross-sectional study carried out from April 02, 2020 to August 31, 2020 at A.C. Camargo Cancer Center (ACCCC), in Sao Paulo, Brazil. Cases were extracted from the Hospital Cancer Registry. COVID-19 lethality rates by histology were calculated; multiple logistic regression was used to identify factors associated with COVID-19 mortality. The log-rank test was applied to compare the survival curves for each variable. Results Of the 411 patients analyzed, 51 (12.4%) died due to COVID-19. Death occurred at an average age of 63 years. The fatality rate was higher for lung (0.333) and hematological (0.213) cancers and was associated with age over 60 years. The greatest chances of death from COVID-19 were in cases of lung (odds ratio, OR, 4.05, 95% confidence interval, CI 1.33–12.34) and hematological (OR 2.17, 95% CI 0.96–4.90) cancers, and in patients currently undergoing cancer treatment (OR 2.77, 95% CI 1.25–6.13). There were no statistical differences in survival by sex, age group, type of insurance, situation at the diagnosis of COVID-19, and histology of cancer for COVID-19. Conclusions Mortality due to COVID-19 in cancer patients is heterogeneous. These findings reinforce the need for individualized strategies for the management of different types of cancer that reduce the risk of death from COVID-19.

Published
2021
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25. Rauchverhalten von Krebspatienten nach Kehlkopfteilresektion: Welche Bedeutung hat die Kausalattribution?

Author

Angela Ulrich, Jochen Ernst, Orlando Guntinas-Lichius, Dorit Engelmann, Andreas Boehm, Anika Münnemann, Alexandra Meyer, Elke-Juliane Schock, Judith Keszte, and Kerstin Breitenstein

Subjects
Gynecology, medicine.medical_specialty, business.industry, 05 social sciences, 050108 psychoanalysis, Partial resection, 03 medical and health sciences, Psychiatry and Mental health, Clinical Psychology, 0302 clinical medicine, medicine, 0501 psychology and cognitive sciences, 030223 otorhinolaryngology, business, Applied Psychology
Abstract

Zusammenfassung Ziel der Studie Etwa 4000 Personen erkranken in Deutschland jährlich an Kehlkopfkrebs. Als einer der wichtigsten Risikofaktoren gilt das Rauchen. Die Studie untersucht den Zusammenhang von Kausalattribution und Rauchverhalten bei Patienten mit Kehlkopfkrebs nach Kehlkopfteilresektion (KTR) und den Einfluss der Kausalattribution auf das Rauchverhalten nach KTR. Methodik In einer multizentrischen prospektiven Kohortenstudie zwischen 2007 und 2013 wurden Patienten mit Kehlkopfkrebs zu 4 Befragungszeitpunkten mit Fragebogen befragt: t1 (zwischen Diagnosestellung und KTR), eine Woche (t2), 3 Monate (t3) und 12 Monate (t4) nach KTR. Nachfolgend werden Daten der Messzeitpunkte t1 und t4 präsentiert. Wesentlicher Gegenstand der deskriptiven Auswertung waren die Kausalattribution (offene Antwort mit anschließender Kodierung entsprechend der wichtigsten Ursachenzuschreibungen sowie früheres und aktuelles Rauchverhalten anhand des DIA-X-Interviewsystems). Die Patienten wurden entsprechend ihrer Kausalattributionen gruppiert und hinsichtlich des Rauchverhaltens verglichen. Ergebnisse Zu den Zeitpunkten t1 und t4 wurden 134 Patienten (Durchschnittsalter 62 Jahre, 93% männlich) interviewt. Ein Viertel der Befragten (25,4%) benennt keine Ursache für die Erkrankung. Wird eine Kausalattribution genannt, ist das Rauchen die am häufigsten beschriebene Ursache (43,3%). Bei aktiven Rauchern dieser Gruppe sinkt die Anzahl der täglich gerauchten Zigaretten nach KTR signifikant um 6 Zigaretten (p=0,001) auf durchschnittlich 11 Zigaretten pro Tag. In keiner Gruppe sinkt der Anteil der Rauchenden signifikant. Schlussfolgerung Die Kausalattribution hat keinen signifikanten Einfluss auf die Rauchentwöhnungsrate. Aktive Raucher reduzieren nach KTR die Menge der Zigaretten signifikant. Dieser Effekt ist noch deutlicher, wenn eine Kausalattribution vorliegt. Indem psychoonkologische Betreuungsangebote, Beratungsgespräche und Rauchentwöhnungsprogramme die Kausalattribution unter Einbezug der Fallspezifik thematisieren, kann dies zu einem prognostisch günstigeren Rauchverhalten nach KTR beitragen.

Published
2021
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26. Safety and efficacy of direct oral anticoagulants under long‐term immunosuppressive therapy after liver, kidney and pancreas transplantation

Author

Adam Herber, Thomas Berg, Daniel Seehofer, Cornelius Engelmann, Sirak Petros, Roland Siegemund, Niklas Aehling, Antje Weimann, and Christian Pfrepper

Subjects
medicine.medical_specialty, medicine.medical_treatment, Administration, Oral, Renal function, 030230 surgery, Liver transplantation, Pancreas transplantation, Kidney, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Edoxaban, Internal medicine, medicine, Humans, Prospective Studies, Prospective cohort study, Retrospective Studies, Immunosuppression Therapy, Transplantation, Rivaroxaban, business.industry, Anticoagulants, Immunosuppression, Kidney Transplantation, Liver, chemistry, 030211 gastroenterology & hepatology, Apixaban, Pancreas Transplantation, business, medicine.drug
Abstract

The safety of direct oral anticoagulants (DOACs) in patients after solid organ transplantation (SOT) is not well defined. This study aimed at describing the safety and efficacy of DOACs in patients after SOT. Patients after kidney and/or liver transplantation under maintenance immunosuppression treated with rivaroxaban (n = 26), apixaban (n = 20) and edoxaban (n = 1) were included. Clinical data were collected retrospectively and using a questionnaire. DOAC plasma levels and thrombin generation (TG) were measured in patients after SOT and compared with nontransplanted controls receiving DOACs. DOACs were administered for 84.6 patient-years. Mean immunosuppressive trough levels after DOAC initiation increased from baseline by 18.8 ± 29.6% compared to 3.0 ± 16.5% in matched controls (P = 0.004), without significant differences in dose adjustments. No transplant rejection or significant change in liver or renal function was observed. There was one major bleeding after the observation period but no thromboembolic complication. DOAC plasma levels reached the expected range in all patients. The intrinsic hemostatic activity in transplanted patients was higher compared to nontransplant controls. Treatment with DOACs after SOT is safe and effective. Immunosuppressive trough levels should be monitored after DOAC initiation, particularly in the early phase after SOT. These data should be confirmed in a prospective study.

Published
2021
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27. Stone-glass curtain wall: designing an outstanding facade in New York City

Author

Michael Engelmann, Franz Hirsch, and Andreas Kübler

Subjects
Engineering, Architectural engineering, Feature (archaeology), business.industry, Full scale, Oculus, Building and Construction, The arts, Architecture, Facade, Curtain wall, Mullion, business, Roof, Civil and Structural Engineering
Abstract

The new World Trade Center complex in New York City rose up into the heights during the last decade. Nine new buildings including 1776 ft tall One WTC and Calatrava’s sculptural Oculus Station cover the 60,000 m2 area in the world’s most outstanding construction site. One spot is still under construction and will host “The Ronald O. Perelman Performing Arts Center”—a new kind of multidisciplinary venue with an astonishing smooth facade made from exceptional stone-glass. The cube-shaped building is 49 × 49 m wide and 42 m tall. A steel roof cantilevers from the inner core and holds hot-rolled steel mullions to carry the curtail wall. The total span is 36 m with one intermediate support only. This encloses a large area interior room for public events, arts and theatre performances. As a special feature, the whole building is covered with stone, in particular 4800 stone-glass insulating glass units grouped in aluminum cassettes carrying four glass panes each. The intention is to present a white four-sided landmark structure with distinguished black veining during the day and a glowing amber-like appearance at night when the interior of the building is illuminated. Stone-glass units have never been used in this scale. Standard PVB interlayers were not an option for the product as it cannot be laminated properly. Therefore, the facade supplier accepted the challenge to design and build using alternative materials. The paper presents the project and its facade design. Numerous additional experimental assessments were conducted—from small scale quasi-static air pressure tests of the glass to full scale performance mock-up tests. Finally, a design process was developed that covers all critical demands of an incomparable project.

Published
2021
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28. International Impact of COVID-19 on the Diagnosis of Heart Disease

Author

Einstein, A. J., Shaw, L. J., Hirschfeld, C., Williams, M. C., Villines, T. C., Better, N., Vitola, J. V., Cerci, R., Dorbala, S., Raggi, P., Choi, A. D., Lu, B., Sinitsyn, V., Sergienko, V., Kudo, T., Norgaard, B. L., Maurovich-Horvat, P., Campisi, R., Milan, E., Louw, L., Allam, A. H., Bhatia, M., Malkovskiy, E., Goebel, B., Cohen, Y., Randazzo, M., Narula, J., Pascual, T. N. B., Pynda, Y., Dondi, M., Gerd Hinterleitner, Paez D., Yao, Lu, Olga, Morozova, Zhuoran, Xu, Juan, Lopez-Mattei, Purvi, Parwani, Mohammad Nawaz Nasery, Artan, Goda, Ervina, Shirka, Rabie, Benlabgaa, Salah, Bouyoucef, Abdelkader, Medjahedi, Qais, Nailli, Mariela, Agolti, Roberto Nicolas Aguero, Maria Del Carmen Alak, Lucia Graciela Alberguina, Guillermo, Arroñada, Andrea, Astesiano, Alfredo, Astesiano, Carolina Bas Norton, Pablo, Benteo, Juan, Blanco, Juan Manuel Bonelli, Jose Javier Bustos, Raul, Cabrejas, Jorge, Cachero, Alejandro, Canderoli, Silvia, Carames, Patrícia, Carrascosa, Ricardo, Castro, Oscar, Cendoya, Luciano Martin Cognigni, Carlos, Collaud, Claudia, Cortes, Javier, Courtis, Daniel, Cragnolino, Mariana, Daicz, Alejandro De La Vega, Silvia Teresa De Maria, Horacio Del Riego, Fernando, Dettori, Alejandro, Deviggiano, Laura, Dragonetti, Mario, Embon, Ruben Emilio Enriquez, Jorge, Ensinas, Fernando, Faccio, Adolfo, Facello, Diego, Garofalo, Ricardo, Geronazzo, Natalia, Gonza, Lucas, Gutierrez, Miguel Angel Guzzo, Victor, Hasbani, Melina, Huerin, Victor, Jäger, Julio Manuel Lewkowicz, Maria Nieves, A López De Munaín, Jose Maria Lotti, Alejandra, Marquez, Osvaldo, Masoli, Edgardo, Mastrovito, Matias, Mayoraz, Graciela Eva Melado, Anibal, Mele, Maria Fernanda Merani, Alejandro Horacio Meretta, Susana, Molteni, Marcos, Montecinos, Eduardo, Noguera, Carlos, Novoa, Claudio Pereyra Sueldo, Sebastian Perez Ascani, Pablo, Pollono, Maria Paula Pujol, Alejandro, Radzinschi, Gustavo, Raimondi, Marcela, Redruello, Marina, Rodríguez, Matías, Rodríguez, Romina Lorena Romero, Arturo Romero Acuña, Federico, Rovaletti, Lucas San Miguel, Lucrecia, Solari, Bruno, Strada, Sonia, Traverso, Sonia Simona Traverzo, Maria Del Huerto Velazquez Espeche, Juan Sebastian Weihmuller, Juan, Wolcan, Susana, Zeffiro, Mari, Sakanyan, Scott, Beuzeville, Raef, Boktor, Patrick, Butler, Jennifer, Calcott, Loretta, Carr, Virgil, Chan, Charles, Chao, Woon, Chong, Mark, Dobson, D'Arne, Downie, Girish, Dwivedi, Barry, Elison, Jean, Engela, Roslyn, Francis, Anand, Gaikwad, Ashok Gangasandra Basavaraj, Bruce, Goodwin, Robert, Greenough, Christian, Hamilton-Craig, Victar, Hsieh, Subodh, Joshi, Karin, Lederer, Kenneth, Lee, Joseph, Lee, John, Magnussen, Nghi, Mai, Gordon, Mander, Fiona, Murton, Dee, Nandurkar, Johanne, Neill, Edward, O'Rourke, Patricia, O'Sullivan, George, Pandos, Kunthi, Pathmaraj, Alexander, Pitman, Rohan, Poulter, Manuja, Premaratne, David, Prior, Lloyd, Ridley, Natalie, Rutherford, Hamid, Salehi, Connor, Saunders, Luke, Scarlett, Sujith, Seneviratne, Deepa, Shetty, Ganesh, Shrestha, Jonathan, Shulman, Vijay, Solanki, Tony, Stanton, Murch, Stuart, Michael, Stubbs, Ian, Swainson, Kim, Taubman, Andrew, Taylor, Paul, Thomas, Steven, Unger, Anthony, Upton, Shankar, Vamadevan, William Van Gaal, Johan, Verjans, Demetrius, Voutnis, Victor, Wayne, Peter, Wilson, David, Wong, Kirby, Wong, John, Younger, Gudrun, Feuchtner, Siroos, Mirzaei, Konrad, Weiss, Natallia, Maroz-Vadalazhskaya, Olivier, Gheysens, Filip, Homans, Rodrigo, Moreno-Reyes, Agnès, Pasquet, Veronique, Roelants, Caroline, M Van De Heyning, Raúl Araujo Ríos, Valentina, Soldat-Stankovic, Sinisa, Stankovic, Maria Helena Albernaz Siqueira, Augusto, Almeida, Paulo Henrique Alves Togni, Jose Henrique Andrade, Luciana, Andrade, Carlos, Anselmi, Roberta, Araújo, Guilherme, Azevedo, Sabbrina, Bezerra, Rodrigo, Biancardi, Gabriel Blacher Grossman, Simone, Brandão, Diego Bromfman Pianta, Lara, Carreira, Bruno, Castro, Tien, Chang, Fernando Cunali Jr, Roberto, Cury, Roberto, Dantas, Fernando de Amorim Fernandes, Andrea De Lorenzo, Robson De Macedo Filho, Fernanda, Erthal, Fabio, Fernandes, Juliano, Fernandes, Thiago Ferreira De Souza, Wilson Furlan Alves, Bruno, Ghini, Luiz, Goncalves, Ilan, Gottlieb, Marcelo, Hadlich, Vinícius, Kameoka, Ronaldo, Lima, Adna, Lima, Rafael Willain Lopes, Ricardo Machado, E Silva, Tiago, Magalhães, Fábio Martins Silva, Luiz Eduardo Mastrocola, Fábio, Medeiros, José Claudio Meneghetti, Vania, Naue, Danilo, Naves, Roberto, Nolasco, Cesar, Nomura, Joao Bruno Oliveira, Eduardo, Paixao, Filipe Penna De Carvalho, Ibraim, Pinto, Priscila, Possetti, Mayra, Quinta, Rodrigo Rizzo Nogueira Ramos, Ricardo, Rocha, Alfredo, Rodrigues, Carlos, Rodrigues, Leila, Romantini, Adelina, Sanches, Sara, Santana, Leonardo Sara da Silva, Paulo, Schvartzman, Cristina Sebastião Matushita, Tiago, Senra, Afonso, Shiozaki, Maria Eduarda Menezes de Siqueira, Cristiano, Siqueira, Paola, Smanio, Carlos Eduardo Soares, José Soares Junior, Marcio Sommer Bittencourt, Bernardo, Spiro, Cláudio Tinoco Mesquita, Jorge, Torreao, Rafael, Torres, Marly, Uellendahl, Guilherme Urpia Monte, Otávia, Veríssimo, Estevan Vieira Cabeda, Felipe Villela Pedras, Roberto, Waltrick, Marcello, Zapparoli, Hamid, Naseer, Marina, Garcheva-Tsacheva, Irena, Kostadinova, Youdaline, Theng, Gad, Abikhzer, Rene, Barette, Benjamin, Chow, Dominique, Dabreo, Matthias, Friedrich, Ria, Garg, Mohammed Nassoh Hafez, Chris, Johnson, Marla, Kiess, Jonathon, Leipsic, Eugene, Leung, Robert, Miller, Anastasia, Oikonomou, Stephan, Probst, Idan, Roifman, Gary, Small, Vikas, Tandon, Adwait, Trivedi, James, White, Katherine, Zukotynski, Jose, Canessa, Gabriel Castro Muñoz, Carmen, Concha, Pablo, Hidalgo, Cesar, Lovera, Teresa, Massardo, Luis Salazar Vargas, Pedro, Abad, Harold, Arturo, Sandra, Ayala, Luis, Benitez, Alberto, Cadena, Carlos, Caicedo, Antonio Calderón Moncayo, Sharon, Gomez, Claudia, T Gutierrez Villamil, Claudia, Jaimes, Juan Luis Londoño Blair, Luz, Pabon, Mauricio, Pineda, Juan Carlos Rojas, Diego, Ruiz, Manuel Valencia Escobar, Andres, Vasquez, Damiana, Vergel, Alejandro, Zuluaga, Isabel Berrocal Gamboa, Gabriel, Castro, Ulises, González, Ana, Baric, Tonci, Batinic, Maja, Franceschi, Maja Hrabak Paar, Mladen, Jukic, Petar, Medakovic, Viktor, Persic, Marina, Prpic, Ante, Punda, Juan Felipe Batista, Juan Manuel Gómez Lauchy, Yamile Marcos Gutierrez, Rayner, Menéndez, Amalia, Peix, Luis, Rochela, Christoforos, Panagidis, Ioannis, Petrou, Vaclav, Engelmann, Milan, Kaminek, Vladimír, Kincl, Otto, Lang, Milan, Simanek, Jawdat, Abdulla, Morten, Bøttcher, Mette, Christensen, Lars Christian Gormsen, Philip, Hasbak, Søren, Hess, Paw, Holdgaard, Allan, Johansen, Kasper, Kyhl, Kristian Altern Øvrehus, Niels Peter Rønnow Sand, Rolf, Steffensen, Anders, Thomassen, Zerahn, Bo, Alfredo, Perez, Giovanni Alejandro Escorza Velez, Mayra Sanchez Velez, Islam Shawky Abdel Aziz, Mahasen, Abougabal, Taghreed, Ahmed, Ahmed, Asfour, Mona, Hassan, Alia, Hassan, Ahmed, Ibrahim, Sameh, Kaffas, Ahmed, Kandeel, Mohamed Mandour Ali, Ahmad, Mansy, Hany, Maurice, Sherif, Nabil, Mahmoud, Shaaban, Ana Camila Flores, Anne, Poksi, Juhani, Knuuti, Velipekka, Kokkonen, Martti, Larikka, Valtteri, Uusitalo, Matthieu, Bailly, Samuel, Burg, Jean-François, Deux, Vincent, Habouzit, Fabien, Hyafil, Olivier, Lairez, Franck, Proffit, Hamza, Regaieg, Laure, Sarda-Mantel, Vania, Tacher, Roman, P Schneider, Harold, Ayetey, George, Angelidis, Aikaterini, Archontaki, Sofia, Chatziioannou, Ioannis, Datseris, Christina, Fragkaki, Panagiotis, Georgoulias, Sophia, Koukouraki, Maria, Koutelou, Eleni, Kyrozi, Evangelos, Repasos, Petros, Stavrou, Pipitsa, Valsamaki, Carla, Gonzalez, Goleat, Gutierrez, Alejandro, Maldonado, Klara, Buga, Ildiko, Garai, Erzsébet, Schmidt, Balint, Szilveszter, Edit, Várady, Nilesh, Banthia, Jinendra Kumar Bhagat, Rishi, Bhargava, Vivek, Bhat, Partha, Choudhury, Vijay Sai Chowdekar, Aparna, Irodi, Shashank, Jain, Elizabeth, Joseph, Sukriti, Kumar, Girijanandan, Mahapatra, Deepanjan, Mitra, Bhagwant Rai Mittal, Ahmad, Ozair, Chetan, Patel, Tapan, Patel, Ravi, Patel, Shivani, Patel, Sudhir, Saxena, Shantanu, Sengupta, Santosh, Singh, Bhanupriya, Singh, Ashwani, Sood, Atul, Verma, Erwin, Affandi, Padma Savenadia Alam, Edison, Edison, Gani, Gunawan, Habusari, Hapkido, Basuki, Hidayat, Aulia, Huda, Anggoro Praja Mukti, Djoko, Prawiro, Erwin Affandi Soeriadi, Hilman, 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Matis, Michael, Mckenna, Tony, Mcrae, Fernando, Mendoza, Michael, Merhige, David, Min, Chanan, Moffitt, Karen, Moncher, Warren, Moore, Shamil, Morayati, Michael, Morris, Mahmud, Mossa-Basha, Zorana, Mrsic, Venkatesh, Murthy, Prashant, Nagpal, Kyle, Napier, Katarina, Nelson, Prabhjot, Nijjar, Medhat, Osman, Edward, Passen, Amit, Patel, Pravin, Patil, Ryan, Paul, Lawrence, Phillips, Venkateshwar, Polsani, Rajaram, Poludasu, Brian, Pomerantz, Thomas, Porter, Ryan, Prentice, Amit, Pursnani, Mark, Rabbat, Suresh, Ramamurti, Florence, Rich, Hiram Rivera Luna, Austin, Robinson, Kim, Robles, Cesar, Rodríguez, Mark, Rorie, John, Rumberger, Raymond, Russell, Philip, Sabra, Diego, Sadler, Mary, Schemmer, U Joseph Schoepf, Samir, Shah, Nishant, Shah, Sujata, Shanbhag, Gaurav, Sharma, Steven, Shayani, Jamshid, Shirani, Pushpa, Shivaram, Steven, Sigman, Mitch, Simon, Ahmad, Slim, David, Smith, Alexandra, Smith, Prem, Soman, Aditya, Sood, Monvadi Barbara Srichai-Parsia, James, Streeter, Albert, T Ahmed Tawakol, Dustin, Thomas, Randall, Thompson, Tara, Torbet, Desiree, Trinidad, Shawn, Ullery, Samuel, Unzek, Seth, Uretsky, Srikanth, Vallurupalli, Vikas, Verma, Alfonso, Waller, Ellen, Wang, Parker, Ward, Gaby, Weissman, George, Wesbey, Kelly, White, David, Winchester, David, Wolinsky, Sandra, Yost, Michael, Zgaljardic, Omar, Alonso, Mario, Beretta, Rodolfo, Ferrando, Miguel, Kapitan, Fernando, Mut, Omoa, Djuraev, Gulnora, Rozikhodjaeva, Ha Le Ngoc, Son Hong Mai, Xuan Canh Nguyen, Einstein, A. J., Shaw, L. J., Hirschfeld, C., Williams, M. C., Villines, T. C., Better, N., Vitola, J. V., Cerci, R., Dorbala, S., Raggi, P., Choi, A. D., Lu, B., Sinitsyn, V., Sergienko, V., Kudo, T., Norgaard, B. L., Maurovich-Horvat, P., Campisi, R., Milan, E., Louw, L., Allam, A. H., Bhatia, M., Malkovskiy, E., Goebel, B., Cohen, Y., Randazzo, M., Narula, J., Pascual, T. N. B., Pynda, Y., Dondi, M., Paez, D., Cuocolo, A., Einstein, A, Shaw, L, Hirschfeld, C, Williams, M, Villines, T, Better, N, Vitola, J, Cerci, R, Dorbala, S, Raggi, P, Choi, A, Lu, B, Sinitsyn, V, Sergienko, V, Kudo, T, Norgaard, B, Maurovich-Horvat, P, Campisi, R, Milan, E, Louw, L, Allam, A, Bhatia, M, Malkovskiy, E, Goebel, B, Cohen, Y, Randazzo, M, Narula, J, Pascual, T, Pynda, Y, Dondi, M, Paez, D, Pacella, S, and Erba, P

Subjects
INCAPS COVID Investigators Group, Heart disease, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Diagnostic Techniques, Cardiovascular, coronavirus, global health, IAEA, Disease, Telehealth, Cardiorespiratory Medicine and Haematology, 030204 cardiovascular system & hematology, Cardiovascular, 0302 clinical medicine, cardiovascular disease, cardiac testing, COVID-19, diagnostic techniques, cardiovascular, health care surveys, heart diseases, humans, international agencies, Pandemic, Global health, 030212 general & internal medicine, COVID-19 Heart Disease, Cause of death, STATEMENT, Heart Disease, International Agencie, Public Health and Health Services, Biomedical Imaging, Cardiology and Cardiovascular Medicine, Human, medicine.medical_specialty, Heart Diseases, 03 medical and health sciences, Clinical Research, medicine, Humans, Personal protective equipment, Heart Disease - Coronary Heart Disease, business.industry, International Agencies, medicine.disease, the, coronaviru, Diagnostic Techniques, Good Health and Well Being, Clinical research, Cardiovascular System & Hematology, Health Care Survey, Health Care Surveys, Emergency medicine, Global Health, business
Abstract

BACKGROUND The coronavirus disease 2019 (COVID-19) pandemic has adversely affected diagnosis and treatment of noncommunicable diseases. Its effects on delivery of diagnostic care for cardiovascular disease, which remains the leading cause of death worldwide, have not been quantified. OBJECTIVES The study sought to assess COVID-19`s impact on global cardiovascular diagnostic procedural volumes and safety practices. METHODS The International Atomic Energy Agency conducted a worldwide survey assessing alterations in cardiovascular procedure volumes and safety practices resulting from COVID-19. Noninvasive and invasive cardiac testing volumes were obtained from participating sites for March and April 2020 and compared with those from March 2019. Availability of personal protective equipment and pandemic-related testing practice changes were ascertained. RESULTS Surveys were submitted from 909 inpatient and outpatient centers performing cardiac diagnostic procedures, in 108 countries. Procedure volumes decreased 42% from March 2019 to March 2020, and 64% from March 2019 to April 2020. Transthoradc echocardiography decreased by 59%, transesophageat echocardiography 76%, and stress tests 78%, which varied between stress modalities. Coronary angiography (invasive or computed tomography) decreased 55% (p < 0.001 for each procedure). hi multivariable regression, significantly greater reduction in procedures occurred for centers in countries with lower gross domestic product. Location in a low-income and lower-middle-income country was associated with an additional 22% reduction in cardiac procedures and less availability of personal protective equipment and teteheatth. CONCLUSIONS COVID-19 was associated with a significant and abrupt reduction in cardiovascular diagnostic testing across the globe, especially affecting the world's economically challenged. Further study of cardiovascular outcomes and COVID-19-related changes in care delivery is warranted. (C) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

Published
2021
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29. ErgoTakt: A novel approach of human-centered balancing of manual assembly lines

Author

Bastian Engelmann, Vito Modesto Manghisi, Markus Wilhelm, A. E. Uva, Volker Bräutigam, Jan Schmitt, and Michele Fiorentino

Subjects
Production line, 0209 industrial biotechnology, Workstation, Assembly digitalization, Ergonomic assessment, Line balancing, Process (engineering), Computer science, media_common.quotation_subject, 02 engineering and technology, 010501 environmental sciences, 01 natural sciences, law.invention, 020901 industrial engineering & automation, Software, law, Function (engineering), 0105 earth and related environmental sciences, General Environmental Science, media_common, business.industry, Automation, Industrial engineering, Term (time), Workforce, General Earth and Planetary Sciences, business
Abstract

Although the increasing use of automation in industry, manual assembly stations are still common and, in some situations, even inevitable. Current practice in manual assembly lines is to balance them using the takt-time of each workstation and harmonize it. However, this approach mostly does not include ergonomic aspects and thus it may lead to workforce musculoskeletal disorders, extended leaves, and demotivation. This paper presents a holistic human-centric optimization method for line balancing using a novel indicator the ErgoTakt. ErgoTakt improves the legacy takt-time and helps to find an optimum between the ergonomic evaluation of an assembly station and its balance in time. The authors used a custom version of the ErgoSentinel Software and a Microsoft Kinect depth camera to perform online and real-time ergonomic assessment. An optimization algorithm is developed to find the best-fitting solution by minimizing a function of the ergonomic RULA-value and the cycle time of each assembly workstation with respect to the worker's ability. The paper presents the concept, the system-setup and preliminary evaluation of an assembly scenario. The results demonstrate that the new approach is feasible and able to optimize an entire manual assembly process chain in terms of both, economic aspects of a well-balanced production line as well as the ergonomic issue of long term human healthy work.

Published
2021
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30. Impact of COVID-19 on Cardiovascular Testing in the United States Versus the Rest of the World

Author

Hirschfeld, Cole B., Shaw, Leslee J., Williams, Michelle C., Lahey, Ryan, Villines, Todd C., Dorbala, Sharmila, Choi, Andrew D., Shah, Nishant R., Bluemke, David A., Berman, Daniel S., Blankstein, Ron, Ferencik, Maros, Narula, Jagat, Winchester, David, Malkovskiy, Eli, Goebel, Benjamin, Randazzo, Michael J., Lopez-Mattei, Juan, Parwani, Purvi, Vitola, Joao V., Cerci, Rodrigo J., Better, Nathan, Raggi, Paolo, Lu, Bin, Sergienko, Vladimir, Sinitsyn, Valentin, Kudo, Takashi, Nørgaard, Bjarne Linde, Maurovich-Horvat, Pál, Cohen, Yosef A., Pascual, Thomas N. B., Pynda, Yaroslav, Dondi, Maurizio, Paez, Diana, Einstein, Andrew J., Cerci, Rodrigo, Hinterleitner, Gerd, Lu, Yao, Morozova, Olga, Xu, Zhuoran, Cohen, Yosef, Randazzo, Michael, Choi, Andrew, Nasery, Mohammad Nawaz, Goda, Artan, Shirka, Ervina, Benlabgaa, Rabie, Bouyoucef, Salah, Medjahedi, Abdelkader, Nailli, Qais, Agolti, Mariela, Aguero, Roberto Nicolas, Alak, Maria del Carmen, Alberguina, Lucia Graciela, Arroñada, Guillermo, Astesiano, Andrea, Astesiano, Alfredo, Norton, Carolina Bas, Benteo, Pablo, Blanco, Juan, Bonelli, Juan Manuel, Bustos, Jose Javier, Cabrejas, Raul, Cachero, Jorge, Campisi, Roxana, Canderoli, Alejandro, Carames, Silvia, Carrascosa, Patrícia, Castro, Ricardo, Cendoya, Oscar, Cognigni, Luciano Martin, Collaud, Carlos, Cortes, Claudia, Courtis, Javier, Cragnolino, Daniel, Daicz, Mariana, De La Vega, Alejandro, De Maria, Silvia Teresa, Del Riego, Horacio, Dettori, Fernando, Deviggiano, Alejandro, Dragonetti, Laura, Embon, Mario, Enriquez, Ruben Emilio, Ensinas, Jorge, Faccio, Fernando, Facello, Adolfo, Garofalo, Diego, Geronazzo, Ricardo, Gonza, Natalia, Gutierrez, Lucas, Guzzo, Miguel Angel, Hasbani, Victor, Huerin, Melina, Jäger, Victor, Lewkowicz, Julio Manuel, Nieves A López De Munaín, Maria, Lotti, Jose Maria, Marquez, Alejandra, Masoli, Osvaldo, Masoli, Osvaldo Horacio, Mastrovito, Edgardo, Mayoraz, Matias, Melado, Graciela Eva, Mele, Anibal, Merani, Maria Fernanda, Meretta, Alejandro Horacio, Molteni, Susana, Montecinos, Marcos, Noguera, Eduardo, Novoa, Carlos, Sueldo, Claudio Pereyra, Ascani, Sebastian Perez, Pollono, Pablo, Pujol, Maria Paula, Radzinschi, Alejandro, Raimondi, Gustavo, Redruello, Marcela, Rodríguez, Marina, Rodríguez, Matías, Romero, Romina Lorena, Acuña, Arturo Romero, Rovaletti, Federico, San Miguel, Lucas, Solari, Lucrecia, Strada, Bruno, Traverso, Sonia, Traverzo, Sonia Simona, Espeche, Maria del Huerto Velazquez, Weihmuller, Juan Sebastian, Wolcan, Juan, Zeffiro, Susana, Sakanyan, Mari, Beuzeville, Scott, Boktor, Raef, Butler, Patrick, Calcott, Jennifer, Carr, Loretta, Chan, Virgil, Chao, Charles, Chong, Woon, Dobson, Mark, Downie, D'Arne, Dwivedi, Girish, Elison, Barry, Engela, Jean, Francis, Roslyn, Gaikwad, Anand, Basavaraj, Ashok Gangasandra, Goodwin, Bruce, Greenough, Robert, Hamilton-Craig, Christian, Hsieh, Victar, Joshi, Subodh, Lederer, Karin, Lee, Kenneth, Lee, Joseph, Magnussen, John, Mai, Nghi, Mander, Gordon, Murton, Fiona, Nandurkar, Dee, Neill, Johanne, O'Rourke, Edward, O'Sullivan, Patricia, Pandos, George, Pathmaraj, Kunthi, Pitman, Alexander, Poulter, Rohan, Premaratne, Manuja, Prior, David, Ridley, Lloyd, Rutherford, Natalie, Salehi, Hamid, Saunders, Connor, Scarlett, Luke, Seneviratne, Sujith, Shetty, Deepa, Shrestha, Ganesh, Shulman, Jonathan, Solanki, Vijay, Stanton, Tony, Stuart, Murch, Stubbs, Michael, Swainson, Ian, Taubman, Kim, Taylor, Andrew, Thomas, Paul, Unger, Steven, Upton, Anthony, Vamadevan, Shankar, Van Gaal, William, Verjans, Johan, Voutnis, Demetrius, Wayne, Victor, Wilson, Peter, Wong, David, Wong, Kirby, Younger, John, Feuchtner, Gudrun, Mirzaei, Siroos, Weiss, Konrad, Maroz-Vadalazhskaya, Natallia, Gheysens, Olivier, Homans, Filip, Moreno-Reyes, Rodrigo, Pasquet, Agnès, Roelants, Veronique, Van De Heyning, Caroline M., Ríos, Raúl Araujo, Soldat-Stankovic, Valentina, Stankovic, Sinisa, Albernaz Siqueira, Maria Helena, Almeida, Augusto, Alves Togni, Paulo Henrique, Andrade, Jose Henrique, Andrade, Luciana, Anselmi, Carlos, Araújo, Roberta, Azevedo, Guilherme, Bezerra, Sabbrina, Biancardi, Rodrigo, Grossman, Gabriel Blacher, Brandão, Simone, Pianta, Diego Bromfman, Carreira, Lara, Castro, Bruno, Chang, Tien, Cunali, Fernando, Cury, Roberto, Dantas, Roberto, de Amorim Fernandes, Fernando, De Lorenzo, Andrea, De Macedo Filho, Robson, Erthal, Fernanda, Fernandes, Fabio, Fernandes, Juliano, De Souza, Thiago Ferreira, Alves, Wilson Furlan, Ghini, Bruno, Goncalves, Luiz, Gottlieb, Ilan, Hadlich, Marcelo, Kameoka, Vinícius, Lima, Ronaldo, Lima, Adna, Lopes, Rafael Willain, Machado e Silva, Ricardo, Magalhães, Tiago, Silva, Fábio Martins, Mastrocola, Luiz Eduardo, Medeiros, Fábio, Meneghetti, José Claudio, Naue, Vania, Naves, Danilo, Nolasco, Roberto, Nomura, Cesar, Oliveira, Joao Bruno, Paixao, Eduardo, De Carvalho, Filipe Penna, Pinto, Ibraim, Possetti, Priscila, Quinta, Mayra, Nogueira Ramos, Rodrigo Rizzo, Rocha, Ricardo, Rodrigues, Alfredo, Rodrigues, Carlos, Romantini, Leila, Sanches, Adelina, Santana, Sara, Sara da Silva, Leonardo, Schvartzman, Paulo, Matushita, Cristina Sebastião, Senra, Tiago, Shiozaki, Afonso, Menezes de Siqueira, Maria Eduarda, Siqueira, Cristiano, Smanio, Paola, Soares, Carlos Eduardo, Junior, José Soares, Bittencourt, Marcio Sommer, Spiro, Bernardo, Mesquita, Cláudio Tinoco, Torreao, Jorge, Torres, Rafael, Uellendahl, Marly, Monte, Guilherme Urpia, Veríssimo, Otávia, Cabeda, Estevan Vieira, Pedras, Felipe Villela, Waltrick, Roberto, Zapparoli, Marcello, Naseer, Hamid, Garcheva-Tsacheva, Marina, Kostadinova, Irena, Theng, Youdaline, Abikhzer, Gad, Barette, Rene, Chow, Benjamin, Dabreo, Dominique, Friedrich, Matthias, Garg, Ria, Hafez, Mohammed Nassoh, Johnson, Chris, Kiess, Marla, Leipsic, Jonathon, Leung, Eugene, Miller, Robert, Oikonomou, Anastasia, Probst, Stephan, Roifman, Idan, Small, Gary, Tandon, Vikas, Trivedi, Adwait, White, James, Zukotynski, Katherine, Canessa, Jose, Muñoz, Gabriel Castro, Concha, Carmen, Hidalgo, Pablo, Lovera, Cesar, Massardo, Teresa, Vargas, Luis Salazar, Abad, Pedro, Arturo, Harold, Ayala, Sandra, Benitez, Luis, Cadena, Alberto, Caicedo, Carlos, Moncayo, Antonio Calderón, Gomez, Sharon, Gutierrez Villamil, Claudia T., Jaimes, Claudia, Londoño, Juan, Londoño Blair, Juan Luis, Pabon, Luz, Pineda, Mauricio, Rojas, Juan Carlos, Ruiz, Diego, Escobar, Manuel Valencia, Vasquez, Andres, Vergel, Damiana, Zuluaga, Alejandro, Gamboa, Isabel Berrocal, Castro, Gabriel, González, Ulises, Baric, Ana, Batinic, Tonci, Franceschi, Maja, Paar, Maja Hrabak, Jukic, Mladen, Medakovic, Petar, Persic, Viktor, Prpic, Marina, Punda, Ante, Batista, Juan Felipe, Gómez Lauchy, Juan Manuel, Gutierrez, Yamile Marcos, Menéndez, Rayner, Peix, Amalia, Rochela, Luis, Panagidis, Christoforos, Petrou, Ioannis, Engelmann, Vaclav, Kaminek, Milan, Kincl, Vladimír, Lang, Otto, Simanek, Milan, Abdulla, Jawdat, Bøttcher, Morten, Christensen, Mette, Gormsen, Lars Christian, Hasbak, Philip, Hess, Søren, Holdgaard, Paw, Johansen, Allan, Kyhl, Kasper, Norgaard, Bjarne Linde, Øvrehus, Kristian Altern, Rønnow Sand, Niels Peter, Steffensen, Rolf, Thomassen, Anders, Zerahn, Bo, Perez, Alfredo, Escorza Velez, Giovanni Alejandro, Velez, Mayra Sanchez, Abdel Aziz, Islam Shawky, Abougabal, Mahasen, Ahmed, Taghreed, Allam, Adel, Asfour, Ahmed, Hassan, Mona, Hassan, Alia, Ibrahim, Ahmed, Kaffas, Sameh, Kandeel, Ahmed, Ali, Mohamed Mandour, Mansy, Ahmad, Maurice, Hany, Nabil, Sherif, Shaaban, Mahmoud, Flores, Ana Camila, Poksi, Anne, Knuuti, Juhani, Kokkonen, Velipekka, Larikka, Martti, Uusitalo, Valtteri, Bailly, Matthieu, Burg, Samuel, Deux, Jean-François, Habouzit, Vincent, Hyafil, Fabien, Lairez, Olivier, Proffit, Franck, Regaieg, Hamza, Sarda-Mantel, Laure, Tacher, Vania, Schneider, Roman P., Ayetey, Harold, Angelidis, George, Archontaki, Aikaterini, Chatziioannou, Sofia, Datseris, Ioannis, Fragkaki, Christina, Georgoulias, Panagiotis, Koukouraki, Sophia, Koutelou, Maria, Kyrozi, Eleni, Repasos, Evangelos, Stavrou, Petros, Valsamaki, Pipitsa, Gonzalez, Carla, Gutierrez, Goleat, Maldonado, Alejandro, Buga, Klara, Garai, Ildiko, Schmidt, Erzsébet, Szilveszter, Balint, Várady, Edit, Banthia, Nilesh, Bhagat, Jinendra Kumar, Bhargava, Rishi, Bhat, Vivek, Bhatia, Mona, Choudhury, Partha, Chowdekar, Vijay Sai, Irodi, Aparna, Jain, Shashank, Joseph, Elizabeth, Kumar, Sukriti, Girijanandan Mahapatra, Prof Dr, Mitra, Deepanjan, Mittal, Bhagwant Rai, Ozair, Ahmad, Patel, Chetan, Patel, Tapan, Patel, Ravi, Patel, Shivani, Saxena, Sudhir, Sengupta, Shantanu, Singh, Santosh, Singh, Bhanupriya, Sood, Ashwani, Verma, Atul, Affandi, Erwin, Alam Edison, Padma Savenadia, Gunawan, Gani, Hapkido, Habusari, Hidayat, Basuki, Huda, Aulia, Mukti, Anggoro Praja, Prawiro, Djoko, Soeriadi, Erwin Affandi, Syawaluddin, Hilman, Albadr, Amjed, Assadi, Majid, Emami, Farshad, Houshmand, Golnaz, Maleki, Majid, Rostami, Maryam Tajik, Zakavi, Seyed Rasoul, Zaid, Eed Abu, Agranovich, Svetlana, Arnson, Yoav, Bar-Shalom, Rachel, Frenkel, Alex, Knafo, Galit, Lugassi, Rachel, Maor Moalem, Israel Shlomo, Mor, Maya, Muskal, Noam, Ranser, Sara, Shalev, Aryeh, Albano, Domenico, Alongi, Pierpaolo, Arnone, Gaspare, Bagatin, Elisa, Baldari, Sergio, Bauckneht, Matteo, Bertelli, Paolo, Bianco, Francesco, Bonfiglioli, Rachele, Boni, Roberto, Bruno, Andrea, Bruno, Isabella, Busnardo, Elena, Califaretti, Elena, Camoni, Luca, Carnevale, Aldo, Casoni, Roberta, Cavallo, Armando Ugo, Cavenaghi, Giorgio, Chierichetti, Franca, Chiocchi, Marcello, Cittanti, Corrado, Colletta, Mauro, Conti, Umberto, Cossu, Alberto, Cuocolo, Alberto, Cuzzocrea, Marco, De Rimini, Maria Luisa, De Vincentis, Giuseppe, Del Giudice, Eleonora, Del Torto, Alberico, Della Tommasina, Veronica, Durmo, Rexhep, Erba, Paola Anna, Evangelista, Laura, Faletti, Riccardo, Faragasso, Evelina, Farsad, Mohsen, Ferro, Paola, Florimonte, Luigia, Frantellizzi, Viviana, Fringuelli, Fabio Massimo, Gatti, Marco, Gaudiano, Angela, Gimelli, Alessia, Giubbini, Raffaele, Giuffrida, Francesca, Ialuna, Salvatore, Laudicella, Riccardo, Leccisotti, Lucia, Leva, Lucia, Liga, Riccardo, Liguori, Carlo, Longo, Giampiero, Maffione, Margherita, Mancini, Maria Elisabetta, Marcassa, Claudio, Milan, Elisa, Nardi, Barbara, Pacella, Sara, Pepe, Giovanna, Pontone, Gianluca, Pulizzi, Sabina, Quartuccio, Natale, Rampin, Lucia, Ricci, Fabrizio, Rossini, Pierluigi, Rubini, Giuseppe, Russo, Vincenzo, Sacchetti, Gian Mauro, Sambuceti, Gianmario, Scarano, Massimo, Sciagrà, Roberto, Sperandio, Massimiliano, Stefanelli, Antonella, Ventroni, Guido, Zoboli, Stefania, Baugh, Dainia, Chambers, Duane, Madu, Ernest, Nunura, Felix, Asano, Hiroshi, Chimura, Chimura Misato, Fujimoto, Shinichiro, Fujisue, Koichiro, Fukunaga, Tomohisa, Fukushima, Yoshimitsu, Fukuyama, Kae, Hashimoto, Jun, Ichikawa, Yasutaka, Iguchi, Nobuo, Imai, Masamichi, Inaki, Anri, Ishimura, Hayato, Isobe, Satoshi, Kadokami, Toshiaki, Kato, Takao, Kumita, Shinichiro, Maruno, Hirotaka, Mataki, Hiroyuki, Miyagawa, Masao, Morimoto, Ryota, Moroi, Masao, Nagamachi, Shigeki, Nakajima, Kenichi, Nakata, Tomoaki, Nakazato, Ryo, Nanasato, Mamoru, Naya, Masanao, Norikane, Takashi, Ohta, Yasutoshi, Okayama, Satoshi, Okizaki, Atsutaka, Otomi, Yoichi, Otsuka, Hideki, Saito, Masaki, Sakata, Sakata Yasushi, Sarai, Masayoshi, Sato, Daisuke, Shiraishi, Shinya, Suwa, Yoshinobu, Takanami, Kentaro, Takehana, Kazuya, Taki, Junichi, Tamaki, Nagara, Taniguchi, Yasuyo, Teragawa, Hiroki, Tomizawa, Nobuo, Tsujita, Kenichi, Umeji, Kyoko, Wakabayashi, Yasushi, Yamada, Shinichiro, Yamazaki, Shinya, Yoneyama, Tatsuya, Rawashdeh, Mohammad, Batyrkhanov, Daultai, Dautov, Tairkhan, Makhdomi, Khalid, Ombati, Kevin, Alkandari, Faridah, Garashi, Masoud, Coie, Tchoyoson Lim, Rajvong, Sonexay, Kalinin, Artem, Kalnina, Marika, Haidar, Mohamad, Komiagiene, Renata, Kviecinskiene, Giedre, Mataciunas, Mindaugas, Vajauskas, Donatas, Picard, Christian, Karim, Noor Khairiah A., Reichmuth, Luise, Samuel, Anthony, Allarakha, Mohammad Aaftaab, Naojee, Ambedhkar Shantaram, Alexanderson-Rosas, Erick, Barragan, Erika, González-Montecinos, Alejandro Becerril, Cabada, Manuel, Rodriguez, Daniel Calderon, Carvajal-Juarez, Isabel, Cortés, Violeta, Cortés, Filiberto, De La Peña, Erasmo, Gama-Moreno, Manlio, González, Luis, Ramírez, Nelsy Gonzalez, Jiménez-Santos, Moisés, Matos, Luis, Monroy, Edgar, Morelos, Martha, Ornelas, Mario, Ortga Ramirez, Jose Alberto, Preciado-Anaya, Andrés, Preciado-Gutiérrez, Óscar Ulises, Barragan, Adriana Puente, Rosales Uvera, Sandra Graciela, Sandoval, Sigelinda, Tomas, Miguel Santaularia, Sierra-Galan, Lilia M., Siu, Silvia, Vallejo, Enrique, Valles, Mario, Faraggi, Marc, Sereegotov, Erdenechimeg, Ilic, Srdja, Ben-Rais, Nozha, Alaoui, Nadia Ismaili, Taleb, Sara, Myo, Khin Pa, Thu, Phyo Si, Ghimire, Ram Kumar, Rajbanshi, Bijoy, Barneveld, Peter, Glaudemans, Andor, Habets, Jesse, Koopmans, Klaas Pieter, Manders, Jeroen, Pool, Stefan, Scholte, Arthur, Scholtens, Asbjørn, Slart, Riemer, Thimister, Paul, Van Asperen, Erik-Jan, Veltman, Niels, Verschure, Derk, Wagenaar, Nils, Edmond, John, Ellis, Chris, Johnson, Kerryanne, Keenan, Ross, Hua, Shaw, Occleshaw, Christopher, Sasse, Alexander, To, Andrew, Van Pelt, Niels, Young, Calum, Cuadra, Teresa, Roque Vanegas, Hector Bladimir, Soli, Idrissa Adamou, Issoufou, Djibrillou Moussa, Ayodele, Tolulope, Madu, Chibuzo, Onimode, Yetunde, Efros-Monsen, Elen, Forsdahl, Signe Helene, Hildre Dimmen, Jenni-Mari, Jørgensen, Arve, Krohn, Isabel, Løvhaugen, Pål, Bråten, Anders Tjellaug, Al Dhuhli, Humoud, Al Kindi, Faiza, Al-Bulushi, Naeema, Jawa, Zabah, Tag, Naima, Afzal, Muhammad Shehzad, Fatima, Shazia, Younis, Muhammad Numair, Riaz, Musab, Saadullah, Mohammad, Herrera, Yariela, Lenturut-Katal, Dora, Vázquez, Manuel Castillo, Ortellado, José, Akhter, Afroza, Cao, Dianbo, Cheung, Stephen, Dai, Xu, Gong, Lianggeng, Han, Dan, Hou, Yang, Li, Caiying, Li, Tao, Li, Dong, Li, Sijin, Liu, Jinkang, Liu, Hui, Ng, Ming Yen, Sun, Kai, Tang, Gongshun, Wang, Jian, Wang, Ximing, Wang, Zhao-Qian, Wang, Yining, Wang, Yifan, Wu, Jiang, Wu, Zhifang, Xia, Liming, Xiao, Jiangxi, Xu, Lei, Yang, Youyou, Yin, Wu, Yu, Jianqun, Yuan, Li, Zhang, Tong, Zhang, Longjiang, Zhang, Yong-Gao, Zhang, Xiaoli, Zhu, Li, Alfaro, Ana, Abrihan, Paz, Barroso, Asela, Cruz, Eric, Gomez, Marie Rhiamar, Magboo, Vincent Peter, Medina, John Michael, Obaldo, Jerry, Pastrana, Davidson, Pawhay, Christian Michael, Quinon, Alvin, Tang, Jeanelle Margareth, Tecson, Bettina, Uson, Kristine Joy, Uy, Mila, Kostkiewicz, Magdalena, Kunikowska, Jolanta, Bettencourt, Nuno, Cantinho, Guilhermina, Ferreira, Antonio, Syed, Ghulam, Arnous, Samer, Atyani, Said, Byrne, Angela, Gleeson, Tadhg, Kerins, David, Meehan, Conor, Murphy, David, Murphy, Mark, Murray, John, O'Brien, Julie, Bang, Ji-In, Bom, Henry, Cho, Sang-Geon, Hong, Chae Moon, Jang, Su Jin, Jeong, Yong Hyu, Kang, Won Jun, Kim, Ji-Young, Lee, Jaetae, Namgung, Chang Kyeong, So, Young, Won, Kyoung Sook, Majstorov, Venjamin, Vavlukis, Marija, Salobir, Barbara Gužic, Štalc, Monika, Benedek, Theodora, Benedek, Imre, Mititelu, Raluca, Stan, Claudiu Adrian, Ansheles, Alexey, Dariy, Olga, Drozdova, Olga, Gagarina, Nina, Gulyaev, Vsevolod Milyevich, Itskovich, Irina, Karalkin, Anatoly, Kokov, Alexander, Migunova, Ekaterina, Pospelov, Viktor, Ryzhkova, Daria, Saifullina, Guzaliya, Sazonova, Svetlana, Shurupova, Irina, Trifonova, Tatjana, Ussov, Wladimir Yurievich, Vakhromeeva, Margarita, Valiullina, Nailya, Zavadovsky, Konstantin, Zhuravlev, Kirill, Alasnag, Mirvat, Okarvi, Subhani, Saranovic, Dragana Sobic, Keng, Felix, Jason See, Jia Hao, Sekar, Ramkumar, Yew, Min Sen, Vondrak, Andrej, Bejai, Shereen, Bennie, George, Bester, Ria, Engelbrecht, Gerrit, Evbuomwan, Osayande, Gongxeka, Harlem, Vuuren, Magritha Jv, Kaplan, Mitchell, Khushica, Purbhoo, Lakhi, Hoosen, Louw, Lizette, Malan, Nico, Milos, Katarina, Modiselle, Moshe, More, Stuart, Naidoo, Mathava, Scholtz, Leonie, Vangu, Mboyo, Aguadé-Bruix, Santiago, Blanco, Isabel, Cabrera, Antonio, Camarero, Alicia, Casáns-Tormo, Irene, Cuellar-Calabria, Hug, Flotats, Albert, Fuentes Cañamero, Maria Eugenia, García, María Elia, Jimenez-Heffernan, Amelia, Leta, Rubén, Diaz, Javier Lopez, Lumbreras, Luis, Marquez-Cabeza, Juan Javier, Martin, Francisco, Martinez de Alegria, Anxo, Medina, Francisco, Canal, Maria Pedrera, Peiro, Virginia, Pubul-Nuñez, Virginia, Rayo Madrid, Juan Ignacio, Rey, Cristina Rodríguez, Perez, Ricardo Ruano, Ruiz, Joaquín, Hernández, Gertrudis Sabatel, Sevilla, Ana, Zeidán, Nahla, Nanayakkara, Damayanthi, Udugama, Chandraguptha, Simonsson, Magnus, Alkadhi, Hatem, Buechel, Ronny Ralf, Burger, Peter, Ceriani, Luca, De Boeck, Bart, Gräni, Christoph, Juillet de Saint Lager Lucas, Alix, Kamani, Christel H., Kawel-Boehm, Nadine, Manka, Robert, Prior, John O., Rominger, Axel, Vallée, Jean-Paul, Khiewvan, Benjapa, Premprabha, Teerapon, Thientunyakit, Tanyaluck, Sellem, Ali, Kir, Kemal Metin, Sayman, Haluk, Sebikali, Mugisha Julius, Muyinda, Zerida, Kmetyuk, Yaroslav, Korol, Pavlo, Mykhalchenko, Olena, Pliatsek, Volodymyr, Satyr, Maryna, Albalooshi, Batool, Ahmed Hassan, Mohamed Ismail, Anderson, Jill, Bedi, Punit, Biggans, Thomas, Bularga, Anda, Bull, Russell, Burgul, Rajesh, Carpenter, John-Paul, Coles, Duncan, Cusack, David, Deshpande, Aparna, Dougan, John, Fairbairn, Timothy, Farrugia, Alexia, Gopalan, Deepa, Gummow, Alistair, Ramkumar, Prasad Guntur, Hamilton, Mark, Harbinson, Mark, Hartley, Thomas, Hudson, Benjamin, Joshi, Nikhil, Kay, Michael, Kelion, Andrew, Khokhar, Azhar, Kitt, Jamie, Lee, Ken, Low, Chen, Mak, Sze Mun, Marousa, Ntouskou, Martin, Jon, Mcalindon, Elisa, Menezes, Leon, Morgan-Hughes, Gareth, Moss, Alastair, Murray, Anthony, Nicol, Edward, Patel, Dilip, Peebles, Charles, Pugliese, Francesca, Luis Rodrigues, Jonathan Carl, Rofe, Christopher, Sabharwal, Nikant, Schofield, Rebecca, Semple, Thomas, Sharma, Naveen, Strouhal, Peter, Subedi, Deepak, Topping, William, Tweed, Katharine, Weir-Mccall, Jonathan, Abbara, Suhny, Abbasi, Taimur, Abbott, Brian, Abohashem, Shady, Abramson, Sandra, Al-Abboud, Tarek, Al-Mallah, Mouaz, Almousalli, Omar, Ananthasubramaniam, Karthikeyan, Kumar, Mohan Ashok, Askew, Jeffrey, Attanasio, Lea, Balmer-Swain, Mallory, Bayer, Richard R., Bernheim, Adam, Bhatti, Sabha, Bieging, Erik, Bloom, Stephen, Blue, Sean, Bluemke, David, Borges, Andressa, Branch, Kelley, Bravo, Paco, Brothers, Jessica, Budoff, Matthew, Bullock-Palmer, Renée, Burandt, Angela, Burke, Floyd W., Bush, Kelvin, Candela, Candace, Capasso, Elizabeth, 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George Kinzfogl, Kircher, Jacqueline, Kirkbride, Rachael, Kontos, Michael, Kottam, Anupama, Krepp, Joseph, Layer, Jay, Lee, Steven H., Leppo, Jeffrey, Lesser, John, Leung, Steve, Lewin, Howard, Litmanovich, Diana, Liu, Yiyan, Magurany, Kathleen, Markowitz, Jeremy, Marn, Amanda, Matis, Stephen E., Mckenna, Michael, Mcrae, Tony, Mendoza, Fernando, Merhige, Michael, Min, David, Moffitt, Chanan, Moncher, Karen, Moore, Warren, Morayati, Shamil, Morris, Michael, Mossa-Basha, Mahmud, Mrsic, Zorana, Murthy, Venkatesh, Nagpal, Prashant, Napier, Kyle, Nelson, Katarina, Nijjar, Prabhjot, Osman, Medhat, Passen, Edward, Patel, Amit, Patil, Pravin, Paul, Ryan, Phillips, Lawrence, Polsani, Venkateshwar, Poludasu, Rajaram, Pomerantz, Brian, Porter, Thomas, Prentice, Ryan, Pursnani, Amit, Rabbat, Mark, Ramamurti, Suresh, Rich, Florence, Luna, Hiram Rivera, Robinson, Austin, Robles, Kim, Rodríguez, Cesar, Rorie, Mark, Rumberger, John, Russell, Raymond, Sabra, Philip, Sadler, Diego, Schemmer, Mary, Schoepf, U. Joseph, Shah, Samir, Shah, Nishant, Shanbhag, Sujata, Sharma, Gaurav, Shayani, Steven, Shirani, Jamshid, Shivaram, Pushpa, Sigman, Steven, Simon, Mitch, Slim, Ahmad, Smith, David, Smith, Alexandra, Soman, Prem, Sood, Aditya, Srichai-Parsia, Monvadi Barbara, Streeter, James, T, Albert, Tawakol, Ahmed, Thomas, Dustin, Thompson, Randall, Torbet, Tara, Trinidad, Desiree, Ullery, Shawn, Unzek, Samuel, Uretsky, Seth, Vallurupalli, Srikanth, Verma, Vikas, Waller, Alfonso, Wang, Ellen, Ward, Parker, Weissman, Gaby, Wesbey, George, White, Kelly, Wolinsky, David, Yost, Sandra, Zgaljardic, Michael, Alonso, Omar, Beretta, Mario, Ferrando, Rodolfo, Kapitan, Miguel, Mut, Fernando, Djuraev, Omoa, Rozikhodjaeva, Gulnora, Le Ngoc, Ha, Mai, Son Hong, Nguyen, Xuan Canh, Hirschfeld, Cole B., Shaw, Leslee J., Williams, Michelle C., Lahey, Ryan, Villines, Todd C., Dorbala, Sharmila, Choi, Andrew D., Shah, Nishant R., Bluemke, David A., Berman, Daniel S., Blankstein, Ron, Ferencik, Maro, Narula, Jagat, Winchester, David, Malkovskiy, Eli, Goebel, Benjamin, Randazzo, Michael J., Lopez-Mattei, Juan, Parwani, Purvi, Vitola, Joao V., Cerci, Rodrigo J., Better, Nathan, Raggi, Paolo, Lu, Bin, Sergienko, Vladimir, Sinitsyn, Valentin, Kudo, Takashi, Nørgaard, Bjarne Linde, Maurovich-Horvat, Pál, Cohen, Yosef A., Pascual, Thomas N. B., Pynda, Yaroslav, Dondi, Maurizio, Paez, Diana, Einstein, Andrew J., Cerci, Rodrigo, Hinterleitner, Gerd, Lu, Yao, Morozova, Olga, Xu, Zhuoran, Cohen, Yosef, Randazzo, Michael, Choi, Andrew, Nasery, Mohammad Nawaz, Goda, Artan, Shirka, Ervina, Benlabgaa, Rabie, Bouyoucef, Salah, Medjahedi, Abdelkader, Nailli, Qai, Agolti, Mariela, Aguero, Roberto Nicola, Alak, Maria del Carmen, Alberguina, Lucia Graciela, Arroñada, Guillermo, Astesiano, Andrea, Astesiano, Alfredo, Norton, Carolina Ba, Benteo, Pablo, Blanco, Juan, Bonelli, Juan Manuel, Bustos, Jose Javier, Cabrejas, Raul, Cachero, Jorge, Campisi, Roxana, Canderoli, Alejandro, Carames, Silvia, Carrascosa, Patrícia, Castro, Ricardo, Cendoya, Oscar, Cognigni, Luciano Martin, Collaud, Carlo, Cortes, Claudia, Courtis, Javier, Cragnolino, Daniel, Daicz, Mariana, De La Vega, Alejandro, De Maria, Silvia Teresa, Del Riego, Horacio, Dettori, Fernando, Deviggiano, Alejandro, Dragonetti, Laura, Embon, Mario, Enriquez, Ruben Emilio, Ensinas, Jorge, Faccio, Fernando, Facello, Adolfo, Garofalo, Diego, Geronazzo, Ricardo, Gonza, Natalia, Gutierrez, Luca, Guzzo, Miguel Angel, Hasbani, Victor, Huerin, Melina, Jäger, Victor, Lewkowicz, Julio Manuel, Nieves A López De Munaín, Maria, Lotti, Jose Maria, Marquez, Alejandra, Masoli, Osvaldo, Masoli, Osvaldo Horacio, Mastrovito, Edgardo, Mayoraz, Matia, Melado, Graciela Eva, Mele, Anibal, Merani, Maria Fernanda, Meretta, Alejandro Horacio, Molteni, Susana, Montecinos, Marco, Noguera, Eduardo, Novoa, Carlo, Sueldo, Claudio Pereyra, Ascani, Sebastian Perez, Pollono, Pablo, Pujol, Maria Paula, Radzinschi, Alejandro, Raimondi, Gustavo, Redruello, Marcela, Rodríguez, Marina, Rodríguez, Matía, Romero, Romina Lorena, Acuña, Arturo Romero, Rovaletti, Federico, San Miguel, Luca, Solari, Lucrecia, Strada, Bruno, Traverso, Sonia, Traverzo, Sonia Simona, Espeche, Maria del Huerto Velazquez, Weihmuller, Juan Sebastian, Wolcan, Juan, Zeffiro, Susana, Sakanyan, Mari, Beuzeville, Scott, Boktor, Raef, Butler, Patrick, Calcott, Jennifer, Carr, Loretta, Chan, Virgil, Chao, Charle, Chong, Woon, Dobson, Mark, Downie, D'Arne, Dwivedi, Girish, Elison, Barry, Engela, Jean, Francis, Roslyn, Gaikwad, Anand, Basavaraj, Ashok Gangasandra, Goodwin, Bruce, Greenough, Robert, Hamilton-Craig, Christian, Hsieh, Victar, Joshi, Subodh, Lederer, Karin, Lee, Kenneth, Lee, Joseph, Magnussen, John, Mai, Nghi, Mander, Gordon, Murton, Fiona, Nandurkar, Dee, Neill, Johanne, O'Rourke, Edward, O'Sullivan, Patricia, Pandos, George, Pathmaraj, Kunthi, Pitman, Alexander, Poulter, Rohan, Premaratne, Manuja, Prior, David, Ridley, Lloyd, Rutherford, Natalie, Salehi, Hamid, Saunders, Connor, Scarlett, Luke, Seneviratne, Sujith, Shetty, Deepa, Shrestha, Ganesh, Shulman, Jonathan, Solanki, Vijay, Stanton, Tony, Stuart, Murch, Stubbs, Michael, Swainson, Ian, Taubman, Kim, Taylor, Andrew, Thomas, Paul, Unger, Steven, Upton, Anthony, Vamadevan, Shankar, Van Gaal, William, Verjans, Johan, Voutnis, Demetriu, Wayne, Victor, Wilson, Peter, Wong, David, Wong, Kirby, Younger, John, Feuchtner, Gudrun, Mirzaei, Siroo, Weiss, Konrad, Maroz-Vadalazhskaya, Natallia, Gheysens, Olivier, Homans, Filip, Moreno-Reyes, Rodrigo, Pasquet, Agnè, Roelants, Veronique, Van De Heyning, Caroline M., Ríos, Raúl Araujo, Soldat-Stankovic, Valentina, Stankovic, Sinisa, Albernaz Siqueira, Maria Helena, Almeida, Augusto, Alves Togni, Paulo Henrique, Andrade, Jose Henrique, Andrade, Luciana, Anselmi, Carlo, Araújo, Roberta, Azevedo, Guilherme, Bezerra, Sabbrina, Biancardi, Rodrigo, Grossman, Gabriel Blacher, Brandão, Simone, Pianta, Diego Bromfman, Carreira, Lara, Castro, Bruno, Chang, Tien, Cunali, Fernando, Cury, Roberto, Dantas, Roberto, de Amorim Fernandes, Fernando, De Lorenzo, Andrea, De Macedo Filho, Robson, Erthal, Fernanda, Fernandes, Fabio, Fernandes, Juliano, De Souza, Thiago Ferreira, Alves, Wilson Furlan, Ghini, Bruno, Goncalves, Luiz, Gottlieb, Ilan, Hadlich, Marcelo, Kameoka, Viníciu, Lima, Ronaldo, Lima, Adna, Lopes, Rafael Willain, Machado e Silva, Ricardo, Magalhães, Tiago, Silva, Fábio Martin, Mastrocola, Luiz Eduardo, Medeiros, Fábio, Meneghetti, José Claudio, Naue, Vania, Naves, Danilo, Nolasco, Roberto, Nomura, Cesar, Oliveira, Joao Bruno, Paixao, Eduardo, De Carvalho, Filipe Penna, Pinto, Ibraim, Possetti, Priscila, Quinta, Mayra, Nogueira Ramos, Rodrigo Rizzo, Rocha, Ricardo, Rodrigues, Alfredo, Rodrigues, Carlo, Romantini, Leila, Sanches, Adelina, Santana, Sara, Sara da Silva, Leonardo, Schvartzman, Paulo, Matushita, Cristina Sebastião, Senra, Tiago, Shiozaki, Afonso, Menezes de Siqueira, Maria Eduarda, Siqueira, Cristiano, Smanio, Paola, Soares, Carlos Eduardo, Junior, José Soare, Bittencourt, Marcio Sommer, Spiro, Bernardo, Mesquita, Cláudio Tinoco, Torreao, Jorge, Torres, Rafael, Uellendahl, Marly, Monte, Guilherme Urpia, Veríssimo, Otávia, Cabeda, Estevan Vieira, Pedras, Felipe Villela, Waltrick, Roberto, Zapparoli, Marcello, Naseer, Hamid, Garcheva-Tsacheva, Marina, Kostadinova, Irena, Theng, Youdaline, Abikhzer, Gad, Barette, Rene, Chow, Benjamin, Dabreo, Dominique, Friedrich, Matthia, Garg, Ria, Hafez, Mohammed Nassoh, Johnson, Chri, Kiess, Marla, Leipsic, Jonathon, Leung, Eugene, Miller, Robert, Oikonomou, Anastasia, Probst, Stephan, Roifman, Idan, Small, Gary, Tandon, Vika, Trivedi, Adwait, White, Jame, Zukotynski, Katherine, Canessa, Jose, Muñoz, Gabriel Castro, Concha, Carmen, Hidalgo, Pablo, Lovera, Cesar, Massardo, Teresa, Vargas, Luis Salazar, Abad, Pedro, Arturo, Harold, Ayala, Sandra, Benitez, Lui, Cadena, Alberto, Caicedo, Carlo, Moncayo, Antonio Calderón, Gomez, Sharon, Gutierrez Villamil, Claudia T., Jaimes, Claudia, Londoño, Juan, Londoño Blair, Juan Lui, Pabon, Luz, Pineda, Mauricio, Rojas, Juan Carlo, Ruiz, Diego, Escobar, Manuel Valencia, Vasquez, Andre, Vergel, Damiana, Zuluaga, Alejandro, Gamboa, Isabel Berrocal, Castro, Gabriel, González, Ulise, Baric, Ana, Batinic, Tonci, Franceschi, Maja, Paar, Maja Hrabak, Jukic, Mladen, Medakovic, Petar, Persic, Viktor, Prpic, Marina, Punda, Ante, Batista, Juan Felipe, Gómez Lauchy, Juan Manuel, Gutierrez, Yamile Marco, Menéndez, Rayner, Peix, Amalia, Rochela, Lui, Panagidis, Christoforo, Petrou, Ioanni, Engelmann, Vaclav, Kaminek, Milan, Kincl, Vladimír, Lang, Otto, Simanek, Milan, Abdulla, Jawdat, Bøttcher, Morten, Christensen, Mette, Gormsen, Lars Christian, Hasbak, Philip, Hess, Søren, Holdgaard, Paw, Johansen, Allan, Kyhl, Kasper, Norgaard, Bjarne Linde, Øvrehus, Kristian Altern, Rønnow Sand, Niels Peter, Steffensen, Rolf, Thomassen, Ander, Zerahn, Bo, Perez, Alfredo, Escorza Velez, Giovanni Alejandro, Velez, Mayra Sanchez, Abdel Aziz, Islam Shawky, Abougabal, Mahasen, Ahmed, Taghreed, Allam, Adel, Asfour, Ahmed, Hassan, Mona, Hassan, Alia, Ibrahim, Ahmed, Kaffas, Sameh, Kandeel, Ahmed, Ali, Mohamed Mandour, Mansy, Ahmad, Maurice, Hany, Nabil, Sherif, Shaaban, Mahmoud, Flores, Ana Camila, Poksi, Anne, Knuuti, Juhani, Kokkonen, Velipekka, Larikka, Martti, Uusitalo, Valtteri, Bailly, Matthieu, Burg, Samuel, Deux, Jean-Françoi, Habouzit, Vincent, Hyafil, Fabien, Lairez, Olivier, Proffit, Franck, Regaieg, Hamza, Sarda-Mantel, Laure, Tacher, Vania, Schneider, Roman P., Ayetey, Harold, Angelidis, George, Archontaki, Aikaterini, Chatziioannou, Sofia, Datseris, Ioanni, Fragkaki, Christina, Georgoulias, Panagioti, Koukouraki, Sophia, Koutelou, Maria, Kyrozi, Eleni, Repasos, Evangelo, Stavrou, Petro, Valsamaki, Pipitsa, Gonzalez, Carla, Gutierrez, Goleat, Maldonado, Alejandro, Buga, Klara, Garai, Ildiko, Schmidt, Erzsébet, Szilveszter, Balint, Várady, Edit, Banthia, Nilesh, Bhagat, Jinendra Kumar, Bhargava, Rishi, Bhat, Vivek, Bhatia, Mona, Choudhury, Partha, Chowdekar, Vijay Sai, Irodi, Aparna, Jain, Shashank, Joseph, Elizabeth, Kumar, Sukriti, Girijanandan Mahapatra, Prof Dr, Mitra, Deepanjan, Mittal, Bhagwant Rai, Ozair, Ahmad, Patel, Chetan, Patel, Tapan, Patel, Ravi, Patel, Shivani, Saxena, Sudhir, Sengupta, Shantanu, Singh, Santosh, Singh, Bhanupriya, Sood, Ashwani, Verma, Atul, Affandi, Erwin, Alam, Edison, Padma, Savenadia, Gunawan, Gani, Hapkido, Habusari, Hidayat, Basuki, Huda, Aulia, Mukti, Anggoro Praja, Prawiro, Djoko, Soeriadi, Erwin Affandi, Syawaluddin, Hilman, Albadr, Amjed, Assadi, Majid, Emami, Farshad, Houshmand, Golnaz, Maleki, Majid, Rostami, Maryam Tajik, Zakavi, Seyed Rasoul, Zaid, Eed Abu, Agranovich, Svetlana, Arnson, Yoav, Bar-Shalom, Rachel, Frenkel, Alex, Knafo, Galit, Lugassi, Rachel, Maor Moalem, Israel Shlomo, Mor, Maya, Muskal, Noam, Ranser, Sara, Shalev, Aryeh, Albano, Domenico, Alongi, Pierpaolo, Arnone, Gaspare, Bagatin, Elisa, Baldari, Sergio, Bauckneht, Matteo, Bertelli, Paolo, Bianco, Francesco, Bonfiglioli, Rachele, Boni, Roberto, Bruno, Andrea, Bruno, Isabella, Busnardo, Elena, Califaretti, Elena, Camoni, Luca, Carnevale, Aldo, Casoni, Roberta, Cavallo, Armando Ugo, Cavenaghi, Giorgio, Chierichetti, Franca, Chiocchi, Marcello, Cittanti, Corrado, Colletta, Mauro, Conti, Umberto, Cossu, Alberto, Cuocolo, Alberto, Cuzzocrea, Marco, De Rimini, Maria Luisa, De Vincentis, Giuseppe, Del Giudice, Eleonora, Del Torto, Alberico, Della Tommasina, Veronica, Durmo, Rexhep, Erba, Paola Anna, Evangelista, Laura, Faletti, Riccardo, Faragasso, Evelina, Farsad, Mohsen, Ferro, Paola, Florimonte, Luigia, Frantellizzi, Viviana, Fringuelli, Fabio Massimo, Gatti, Marco, Gaudiano, Angela, Gimelli, Alessia, Giubbini, Raffaele, Giuffrida, Francesca, Ialuna, Salvatore, Laudicella, Riccardo, Leccisotti, Lucia, Leva, Lucia, Liga, Riccardo, Liguori, Carlo, Longo, Giampiero, Maffione, Margherita, Mancini, Maria Elisabetta, Marcassa, Claudio, Milan, Elisa, Nardi, Barbara, Pacella, Sara, Pepe, Giovanna, Pontone, Gianluca, Pulizzi, Sabina, Quartuccio, Natale, Rampin, Lucia, Ricci, Fabrizio, Rossini, Pierluigi, Rubini, Giuseppe, Russo, Vincenzo, Sacchetti, Gian Mauro, Sambuceti, Gianmario, Scarano, Massimo, Sciagrà, Roberto, Sperandio, Massimiliano, Stefanelli, Antonella, Ventroni, Guido, Zoboli, Stefania, Baugh, Dainia, Chambers, Duane, Madu, Ernest, Nunura, Felix, Asano, Hiroshi, Chimura, Chimura Misato, Fujimoto, Shinichiro, Fujisue, Koichiro, Fukunaga, Tomohisa, Fukushima, Yoshimitsu, Fukuyama, Kae, Hashimoto, Jun, Ichikawa, Yasutaka, Iguchi, Nobuo, Imai, Masamichi, Inaki, Anri, Ishimura, Hayato, Isobe, Satoshi, Kadokami, Toshiaki, Kato, Takao, Kumita, Shinichiro, Maruno, Hirotaka, Mataki, Hiroyuki, Miyagawa, Masao, Morimoto, Ryota, Moroi, Masao, Nagamachi, Shigeki, Nakajima, Kenichi, Nakata, Tomoaki, Nakazato, Ryo, Nanasato, Mamoru, Naya, Masanao, Norikane, Takashi, Ohta, Yasutoshi, Okayama, Satoshi, Okizaki, Atsutaka, Otomi, Yoichi, Otsuka, Hideki, Saito, Masaki, Sakata, Sakata Yasushi, Sarai, Masayoshi, Sato, Daisuke, Shiraishi, Shinya, Suwa, Yoshinobu, Takanami, Kentaro, Takehana, Kazuya, Taki, Junichi, Tamaki, Nagara, Taniguchi, Yasuyo, Teragawa, Hiroki, Tomizawa, Nobuo, Tsujita, Kenichi, Umeji, Kyoko, Wakabayashi, Yasushi, Yamada, Shinichiro, Yamazaki, Shinya, Yoneyama, Tatsuya, Rawashdeh, Mohammad, Batyrkhanov, Daultai, Dautov, Tairkhan, Makhdomi, Khalid, Ombati, Kevin, Alkandari, Faridah, Garashi, Masoud, Coie, Tchoyoson Lim, Rajvong, Sonexay, Kalinin, Artem, Kalnina, Marika, Haidar, Mohamad, Komiagiene, Renata, Kviecinskiene, Giedre, Mataciunas, Mindauga, Vajauskas, Donata, Picard, Christian, Karim, Noor Khairiah A., Reichmuth, Luise, Samuel, Anthony, Allarakha, Mohammad Aaftaab, Naojee, Ambedhkar Shantaram, Alexanderson-Rosas, Erick, Barragan, Erika, González-Montecinos, Alejandro Becerril, Cabada, Manuel, Rodriguez, Daniel Calderon, Carvajal-Juarez, Isabel, Cortés, Violeta, Cortés, Filiberto, De La Peña, Erasmo, Gama-Moreno, Manlio, González, Lui, Ramírez, Nelsy Gonzalez, Jiménez-Santos, Moisé, Matos, Lui, Monroy, Edgar, Morelos, Martha, Ornelas, Mario, Ortga Ramirez, Jose Alberto, Preciado-Anaya, André, Preciado-Gutiérrez, Óscar Ulise, Barragan, Adriana Puente, Rosales Uvera, Sandra Graciela, Sandoval, Sigelinda, Tomas, Miguel Santaularia, Sierra-Galan, Lilia M., Siu, Silvia, Vallejo, Enrique, Valles, Mario, Faraggi, Marc, Sereegotov, Erdenechimeg, Ilic, Srdja, Ben-Rais, Nozha, Alaoui, Nadia Ismaili, Taleb, Sara, Myo, Khin Pa, Thu, Phyo Si, Ghimire, Ram Kumar, Rajbanshi, Bijoy, Barneveld, Peter, Glaudemans, Andor, Habets, Jesse, Koopmans, Klaas Pieter, Manders, Jeroen, Pool, Stefan, Scholte, Arthur, Scholtens, Asbjørn, Slart, Riemer, Thimister, Paul, Van Asperen, Erik-Jan, Veltman, Niel, Verschure, Derk, Wagenaar, Nil, Edmond, John, Ellis, Chri, Johnson, Kerryanne, Keenan, Ro, Hua, Shaw, Occleshaw, Christopher, Sasse, Alexander, To, Andrew, Van Pelt, Niel, Young, Calum, Cuadra, Teresa, Roque Vanegas, Hector Bladimir, Soli, Idrissa Adamou, Issoufou, Djibrillou Moussa, Ayodele, Tolulope, Madu, Chibuzo, Onimode, Yetunde, Efros-Monsen, Elen, Forsdahl, Signe Helene, Hildre Dimmen, Jenni-Mari, Jørgensen, Arve, Krohn, Isabel, Løvhaugen, Pål, Bråten, Anders Tjellaug, Al Dhuhli, Humoud, Al Kindi, Faiza, Al-Bulushi, Naeema, Jawa, Zabah, Tag, Naima, Afzal, Muhammad Shehzad, Fatima, Shazia, Younis, Muhammad Numair, Riaz, Musab, Saadullah, Mohammad, Herrera, Yariela, Lenturut-Katal, Dora, Vázquez, Manuel Castillo, Ortellado, José, Akhter, Afroza, Cao, Dianbo, Cheung, Stephen, Dai, Xu, Gong, Lianggeng, Han, Dan, Hou, Yang, Li, Caiying, Li, Tao, Li, Dong, Li, Sijin, Liu, Jinkang, Liu, Hui, Ng, Ming Yen, Sun, Kai, Tang, Gongshun, Wang, Jian, Wang, Ximing, Wang, Zhao-Qian, Wang, Yining, Wang, Yifan, Wu, Jiang, Wu, Zhifang, Xia, Liming, Xiao, Jiangxi, Xu, Lei, Yang, Youyou, Yin, Wu, Yu, Jianqun, Yuan, Li, Zhang, Tong, Zhang, Longjiang, Zhang, Yong-Gao, Zhang, Xiaoli, Zhu, Li, Alfaro, Ana, Abrihan, Paz, Barroso, Asela, Cruz, Eric, Gomez, Marie Rhiamar, Magboo, Vincent Peter, Medina, John Michael, Obaldo, Jerry, Pastrana, Davidson, Pawhay, Christian Michael, Quinon, Alvin, Tang, Jeanelle Margareth, Tecson, Bettina, Uson, Kristine Joy, Uy, Mila, Kostkiewicz, Magdalena, Kunikowska, Jolanta, Bettencourt, Nuno, Cantinho, Guilhermina, Ferreira, Antonio, Syed, Ghulam, Arnous, Samer, Atyani, Said, Byrne, Angela, Gleeson, Tadhg, Kerins, David, Meehan, Conor, Murphy, David, Murphy, Mark, Murray, John, O'Brien, Julie, Bang, Ji-In, Bom, Henry, Cho, Sang-Geon, Hong, Chae Moon, Jang, Su Jin, Jeong, Yong Hyu, Kang, Won Jun, Kim, Ji-Young, Lee, Jaetae, Namgung, Chang Kyeong, So, Young, Won, Kyoung Sook, Majstorov, Venjamin, Vavlukis, Marija, Salobir, Barbara Gužic, Štalc, Monika, Benedek, Theodora, Benedek, Imre, Mititelu, Raluca, Stan, Claudiu Adrian, Ansheles, Alexey, Dariy, Olga, Drozdova, Olga, Gagarina, Nina, Gulyaev, Vsevolod Milyevich, Itskovich, Irina, Karalkin, Anatoly, Kokov, Alexander, Migunova, Ekaterina, Pospelov, Viktor, Ryzhkova, Daria, Saifullina, Guzaliya, Sazonova, Svetlana, Shurupova, Irina, Trifonova, Tatjana, Ussov, Wladimir Yurievich, Vakhromeeva, Margarita, Valiullina, Nailya, Zavadovsky, Konstantin, Zhuravlev, Kirill, Alasnag, Mirvat, Okarvi, Subhani, Saranovic, Dragana Sobic, Keng, Felix, Jason See, Jia Hao, Sekar, Ramkumar, Yew, Min Sen, Vondrak, Andrej, Bejai, Shereen, Bennie, George, Bester, Ria, Engelbrecht, Gerrit, Evbuomwan, Osayande, Gongxeka, Harlem, Vuuren, Magritha Jv, Kaplan, Mitchell, Khushica, Purbhoo, Lakhi, Hoosen, Louw, Lizette, Malan, Nico, Milos, Katarina, Modiselle, Moshe, More, Stuart, Naidoo, Mathava, Scholtz, Leonie, Vangu, Mboyo, Aguadé-Bruix, Santiago, Blanco, Isabel, Cabrera, Antonio, Camarero, Alicia, Casáns-Tormo, Irene, Cuellar-Calabria, Hug, Flotats, Albert, Fuentes Cañamero, Maria Eugenia, García, María Elia, Jimenez-Heffernan, Amelia, Leta, Rubén, Diaz, Javier Lopez, Lumbreras, Lui, Marquez-Cabeza, Juan Javier, Martin, Francisco, Martinez de Alegria, Anxo, Medina, Francisco, Canal, Maria Pedrera, Peiro, Virginia, Pubul-Nuñez, Virginia, Rayo Madrid, Juan Ignacio, Rey, Cristina Rodríguez, Perez, Ricardo Ruano, Ruiz, Joaquín, Hernández, Gertrudis Sabatel, Sevilla, Ana, Zeidán, Nahla, Nanayakkara, Damayanthi, Udugama, Chandraguptha, Simonsson, Magnu, Alkadhi, Hatem, Buechel, Ronny Ralf, Burger, Peter, Ceriani, Luca, De Boeck, Bart, Gräni, Christoph, Juillet de Saint Lager Lucas, Alix, Kamani, Christel H., Kawel-Boehm, Nadine, Manka, Robert, Prior, John O., Rominger, Axel, Vallée, Jean-Paul, Khiewvan, Benjapa, Premprabha, Teerapon, Thientunyakit, Tanyaluck, Sellem, Ali, Kir, Kemal Metin, Sayman, Haluk, Sebikali, Mugisha Juliu, Muyinda, Zerida, Kmetyuk, Yaroslav, Korol, Pavlo, Mykhalchenko, Olena, Pliatsek, Volodymyr, Satyr, Maryna, Albalooshi, Batool, Ahmed Hassan, Mohamed Ismail, Anderson, Jill, Bedi, Punit, Biggans, Thoma, Bularga, Anda, Bull, Russell, Burgul, Rajesh, Carpenter, John-Paul, Coles, Duncan, Cusack, David, Deshpande, Aparna, Dougan, John, Fairbairn, Timothy, Farrugia, Alexia, Gopalan, Deepa, Gummow, Alistair, Ramkumar, Prasad Guntur, Hamilton, Mark, Harbinson, Mark, Hartley, Thoma, Hudson, Benjamin, Joshi, Nikhil, Kay, Michael, Kelion, Andrew, Khokhar, Azhar, Kitt, Jamie, Lee, Ken, Low, Chen, Mak, Sze Mun, Marousa, Ntouskou, Martin, Jon, Mcalindon, Elisa, Menezes, Leon, Morgan-Hughes, Gareth, Moss, Alastair, Murray, Anthony, Nicol, Edward, Patel, Dilip, Peebles, Charle, Pugliese, Francesca, Luis Rodrigues, Jonathan Carl, Rofe, Christopher, Sabharwal, Nikant, Schofield, Rebecca, Semple, Thoma, Sharma, Naveen, Strouhal, Peter, Subedi, Deepak, Topping, William, Tweed, Katharine, Weir-Mccall, Jonathan, Abbara, Suhny, Abbasi, Taimur, Abbott, Brian, Abohashem, Shady, Abramson, Sandra, Al-Abboud, Tarek, Al-Mallah, Mouaz, Almousalli, Omar, Ananthasubramaniam, Karthikeyan, Kumar, Mohan Ashok, Askew, Jeffrey, Attanasio, Lea, Balmer-Swain, Mallory, Bayer, Richard R., Bernheim, Adam, Bhatti, Sabha, Bieging, Erik, Bloom, Stephen, Blue, Sean, Bluemke, David, Borges, Andressa, Branch, Kelley, Bravo, Paco, Brothers, Jessica, Budoff, Matthew, Bullock-Palmer, Renée, Burandt, Angela, Burke, Floyd W., Bush, Kelvin, Candela, Candace, Capasso, Elizabeth, Cavalcante, Joao, Chang, Donald, Chatterjee, Saurav, Chatzizisis, Yianni, Cheezum, Michael, Chen, Tiffany, Chen, Jennifer, Chen, Marcu, Clarcq, Jame, Cordero, Ayreen, Crim, Matthew, Danciu, Sorin, Decter, Bruce, Dhruva, Nimish, Doherty, Neil, Doukky, Rami, Dunbar, Anjori, Duvall, William, Edwards, Rachael, Esquitin, Kerry, Farah, Husam, Fentanes, Emilio, Fisher, Daniel, Fitzpatrick, Daniel, Foster, Cameron, Fuisz, Tony, Gannon, Michael, Gastner, Lori, Gerson, Myron, Ghoshhajra, Brian, Goldberg, Alan, Goldner, Brian, Gonzalez, Jorge, Gore, Rosco, Gracia-López, Sandra, Hage, Fadi, Haider, Agha, Haider, Sofia, Hamirani, Yasmin, Hassen, Karen, Hatfield, Mallory, Hawkins, Carolyn, Hawthorne, Katie, Heath, Nichola, Hendel, Robert, Hernandez, Phillip, Hill, Gregory, Horgan, Stephen, Huffman, Jeff, Hurwitz, Lynne, Iskandrian, Ami, Janardhanan, Rajesh, Jellis, Christine, Jerome, Scott, Kalra, Dinesh, Kaviratne, Summanther, Kay, Fernando, Kelly, Faith, Khalique, Omar, Kinkhabwala, Mona, Iii, George Kinzfogl, Kircher, Jacqueline, Kirkbride, Rachael, Kontos, Michael, Kottam, Anupama, Krepp, Joseph, Layer, Jay, Lee, Steven H., Leppo, Jeffrey, Lesser, John, Leung, Steve, Lewin, Howard, Litmanovich, Diana, Liu, Yiyan, Magurany, Kathleen, Markowitz, Jeremy, Marn, Amanda, Matis, Stephen E., Mckenna, Michael, Mcrae, Tony, Mendoza, Fernando, Merhige, Michael, Min, David, Moffitt, Chanan, Moncher, Karen, Moore, Warren, Morayati, Shamil, Morris, Michael, Mossa-Basha, Mahmud, Mrsic, Zorana, Murthy, Venkatesh, Nagpal, Prashant, Napier, Kyle, Nelson, Katarina, Nijjar, Prabhjot, Osman, Medhat, Passen, Edward, Patel, Amit, Patil, Pravin, Paul, Ryan, Phillips, Lawrence, Polsani, Venkateshwar, Poludasu, Rajaram, Pomerantz, Brian, Porter, Thoma, Prentice, Ryan, Pursnani, Amit, Rabbat, Mark, Ramamurti, Suresh, Rich, Florence, Luna, Hiram Rivera, Robinson, Austin, Robles, Kim, Rodríguez, Cesar, Rorie, Mark, Rumberger, John, Russell, Raymond, Sabra, Philip, Sadler, Diego, Schemmer, Mary, Schoepf, U. Joseph, Shah, Samir, Shah, Nishant, Shanbhag, Sujata, Sharma, Gaurav, Shayani, Steven, Shirani, Jamshid, Shivaram, Pushpa, Sigman, Steven, Simon, Mitch, Slim, Ahmad, Smith, David, Smith, Alexandra, Soman, Prem, Sood, Aditya, Srichai-Parsia, Monvadi Barbara, Streeter, Jame, T, Albert, Tawakol, Ahmed, Thomas, Dustin, Thompson, Randall, Torbet, Tara, Trinidad, Desiree, Ullery, Shawn, Unzek, Samuel, Uretsky, Seth, Vallurupalli, Srikanth, Verma, Vika, Waller, Alfonso, Wang, Ellen, Ward, Parker, Weissman, Gaby, Wesbey, George, White, Kelly, Wolinsky, David, Yost, Sandra, Zgaljardic, Michael, Alonso, Omar, Beretta, Mario, Ferrando, Rodolfo, Kapitan, Miguel, Mut, Fernando, Djuraev, Omoa, Rozikhodjaeva, Gulnora, Le Ngoc, Ha, Mai, Son Hong, Nguyen, Xuan Canh, Hirschfeld, C, Shaw, L, Williams, M, Lahey, R, Villines, T, Dorbala, S, Choi, A, Shah, N, Bluemke, D, Berman, D, Blankstein, R, Ferencik, M, Narula, J, Winchester, D, Malkovskiy, E, Goebel, B, Randazzo, M, Lopez-Mattei, J, Parwani, P, Vitola, J, Cerci, R, Better, N, Raggi, P, Lu, B, Sergienko, V, Sinitsyn, V, Kudo, T, Nørgaard, B, Maurovich-Horvat, P, Cohen, Y, Pascual, T, Pynda, Y, Dondi, M, Paez, D, Einstein, A, and Erba, P

Subjects
Aging, Coronavirus disease 2019 (COVID-19), Clinical Sciences, coronavirus, Disease, 030204 cardiovascular system & hematology, Cardiorespiratory Medicine and Haematology, Cardiovascular, 030218 nuclear medicine & medical imaging, NO, 03 medical and health sciences, 0302 clinical medicine, COVID-19 Testing, Cardiovascular procedures, Predictive Value of Tests, cardiovascular disease, Clinical Research, Environmental health, INCAPS-COVID Investigators Group, Pandemic, Volume reduction, Medicine, Humans, Radiology, Nuclear Medicine and imaging, cardiovascular imaging, diagnostic cardiovascular procedure, Pandemics, business.industry, SARS-CoV-2, Prevention, COVID-19, Health Services, United States/epidemiology, United States, Invasive coronary angiography, coronaviru, Heart Disease, Good Health and Well Being, MYOCARDIAL-INFARCTION, Cardiovascular System & Hematology, Predictive value of tests, HOSPITAL ADMISSIONS, Cardiology and Cardiovascular Medicine, Early phase, business
Abstract

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-U.S. institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection.

Published
2021
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31. Indicators of Secretory Activation in Mothers of Preterm Very Low Birth Weight Infants

Author

Charlene Krueger, Sandra E. Sullivan, Clara Engelmann, Martina Mueller, Leslie A. Parker, and Nicole Cacho

Subjects
medicine.medical_specialty, Breast pumping, Milk, Human, Obstetrics, business.industry, Infant, Newborn, Breastfeeding, Infant, Mothers, Obstetrics and Gynecology, Low birth weight, Breast Feeding, medicine, Humans, Infant, Very Low Birth Weight, Female, medicine.symptom, business, Infant, Premature
Abstract

BackgroundInconsistent information exists regarding indicators of secretory activation in mothers delivering very low birth weight infants.Research aimsTo compare time to the onset of secretory activation using three separate indicators. A secondary aim examined the association between indicators of secretory activation and milk production.MethodsIndicators of secretory activation included maternal perception, volume attainment (production of ≥ 20 mL in two consecutive expression sessions) and biomarkers (sodium and lactose) obtained at volume attainment. Milk production was measured on Days 1–7 and then weekly for 6 weeks.ResultsIn 69 mothers of infants born ≤ 32 weeks’ gestation and < 1500 g, we found no correlation in time to secretory activation between indicators. Earlier volume attainment was associated with increased milk production on Days 1–7, 14, 21, and 28 (all p < .007). Participants who exhibited both normal lactose and sodium levels produced more milk on Days 28 and 42 ( p = .028 and .011), those with only normal lactose levels produced more on Day 42 ( p = .026) and those with only normal sodium levels on Day 28 ( p = .036). Earlier secretory activation by volume attainment was associated with increased expression frequency during Days 2–5 (all p < .014) and participants with normal biomarkers expressed more frequently during Days 2–5 (all p < .020).ConclusionMothers of very low birth weight infants are at risk for delayed secretory activation, which may decrease their milk production. Frequent expression during the first 5 days postpartum may promote earlier secretory activation. Valid methods of determining secretory activation are necessary to develop interventions promoting earlier secretory activation.

Published
2020
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32. Donor-to-recipient transmission and reactivation in a kidney transplant recipient of an inherited chromosomally integrated HHV-6A: Evidence and outcomes

Author

Vivien Petit, Bhupesh K. Prusty, Paul Chamley, Emmanuelle Leteurtre, Romain Gerard, François Glowacki, Agathe Baras, Didier Hober, François Provôt, Antoine Decaestecker, Marc Hazzan, Florence Moulonguet, Emmanuel Faure, Jean-Baptiste Gibier, Victor Fages, Mehdi Maanaoui, Agnès Gautheret-Dejean, Pascale Bonnafous, and Ilka Engelmann

Subjects
Transplantation, Kidney, medicine.diagnostic_test, business.industry, viruses, Viral Genes, virus diseases, 030230 surgery, Genome, Virology, Kidney transplant recipient, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Infectious disease (medical specialty), medicine, Immunology and Allergy, Pharmacology (medical), Solid organ transplantation, business, Viral load, Fluorescence in situ hybridization
Abstract

Human herpesvirus (HHV)-6A can be inherited and chromosomally integrated (iciHHV-6A), and donor-to-recipient transmission has been reported in solid organ transplant. However, when HHV-6A reactivation happens after transplant, the source of HHV-6A is often not evident and its pathogenicity remains unclear. Here, we present an exhaustive case of donor-to-recipient transmission and reactivation of iciHHV-6A through kidney transplant. The absence of HHV-6A genome from the nails of the recipient excluded a recipient-related iciHHV-6A. Viral loads > 7 log10 copies/106 cells in donor blood samples and similarities of U38, U39, U69, and U100 viral genes between donor, recipient, and previously published iciHHV-6A strains are proof of donor-related transmission. Detection of noncoding HHV-6 snc-RNA14 using fluorescence in situ hybridization analysis and immunofluorescence staining of HHV-6A gp82/gp105 late proteins on kidney biopsies showed evidence of reactivation in the transplanted kidney. Because HHV-6A reactivation can be life threatening in immunocompromised patients, we provide several tools to help during the complete screening and diagnosis.

Published
2020
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33. IgA Triggers Cell Death of Neutrophils When Primed by Inflammatory Mediators

Author

Olivia Joan Adams, Valentin Djonov, Marius Lötscher, Thomas Kaufmann, Christoph Schneider, Christoph Mueller, Fritz Daudel, Stephan von Gunten, Marc Wehrli, Christian Münz, Ruslan Hlushchuk, Kayluz Frias Boligan, Daniëlle Verschoor, Peter M. Villiger, Cédric Vonarburg, Frank Seibold, Hans-Uwe Simon, Nikhil Yawalkar, Fabiola Cortinas-Elizondo, Sylvia Miescher, Christine Engelmann, University of Zurich, and von Gunten, Stephan

Subjects
Programmed cell death, Cell Survival, Neutrophils, p38 mitogen-activated protein kinases, Primary Cell Culture, Immunology, Apoptosis, 610 Medicine & health, Disease, 10263 Institute of Experimental Immunology, Arthritis, Rheumatoid, Sepsis, Mice, 03 medical and health sciences, 0302 clinical medicine, Immune system, Crohn Disease, hemic and lymphatic diseases, Animals, Humans, Immunology and Allergy, Medicine, Macrophage, Cells, Cultured, PI3K/AKT/mTOR pathway, 2403 Immunology, business.industry, Macrophages, Immunoglobulins, Intravenous, medicine.disease, Coculture Techniques, Immunoglobulin A, Rheumatoid arthritis, 2723 Immunology and Allergy, 570 Life sciences, biology, business, 030215 immunology
Abstract

IVIG preparations consisting of pooled IgG are increasingly used for the treatment of autoimmune diseases. IVIG is known to regulate the viability of immune cells, including neutrophils. We report that plasma-derived IgA efficiently triggers death of neutrophils primed by cytokines or TLR agonists. IgA-mediated programmed neutrophil death was PI3K-, p38 MAPK–, and JNK-dependent and evoked anti-inflammatory cytokines in macrophage cocultures. Neutrophils from patients with acute Crohn's disease, rheumatoid arthritis, or sepsis were susceptible to both IgA- and IVIG-mediated death. In contrast to IVIG, IgA did not promote cell death of quiescent neutrophils. Our findings suggest that plasma-derived IgA might provide a therapeutic option for the treatment of neutrophil-associated inflammatory disorders.

Published
2020
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34. Impact on disease mortality of clinical, biological, and virological characteristics at hospital admission and overtime in COVID‐19 patients

Author

Yazdanpanah, Yazdan, DIALLO, Alpha, PAUL, Christelle, MERCIER, Noémie, LE MESTRE, Soizic, PETROV‐SANCHEZ, Ventzislava, ANDREJAK, Claire, CHIROUZE, Catherine, MALVY, Denis, DEPLANQUE, Dominique, DUBOS, François, ROSSIGNOL, Patrick, ETIENNE, Manuel, ROSSIGNOL, Bénédicte, LEVY‐MARCHAL, Claire, GILG, Morgane, GIGANTE, Tristan, Marine, BELUZE, HULOT, Jean‐Sebastien, CHAIR, Anissa, KHALIL, Antoine, VISSEAUX, Benoit, COUFFIGNAL, Camille, ROY, Carine, LAOUÉNAN, Cédric, DA SILVEIRA, Charlene, TARDIVON, Coralie, BACHELET, Delphine, DESCAMPS, Diane, MENTRÉ, France, BOMPART, François, LESCURE, François‐Xavier, PEYTAVIN, Gilles, GORENNE, Isabelle, HOFFMANN, Isabelle, GHOSN, Jade, Christophe LUCET, Jean, TIMSIT, Jean‐François, MULLAERT, Jimmy, BHAVSAR, Krishna, BOUADMA, Lila, TAGHERSET, Lysa, TELLIER, Marie‐Capucine, DEBRAY, Marie‐Pierre, ESPOSITO‐FARESE, Marina, SCHNEIDER, Marion, LE, Minh, ETTALHAOUI, Nadia, SI MOHAMMED, Nassima, GAULT, Nathalie, PEIFFER‐SMADJA, Nathan, KEFIF, Ouifiya, ELOY, Philippine, LE HINGRAT, Quentin, KALI, Sabrina, LARIBI, Samira, TUBIANA, Sarah, TRIOUX, Théo, DUVAL, Xavier, VANEL, Noémie, PICONE, Olivier, BASMACI, Romain, ANGOULVANT, François, KAGUELIDOU, Florentia, PAGES, Justine, VEISLINGER, Aurélie, TUAL, Christelle, PAPADOPOULOS, Aurélie, ESPEROU, Hélène, JAAFOURA, Salma, COUFFIN‐CADIERGUES, Sandrine, COELHO, Alexandra, HOCTIN, Alexandre, DIOUF, Alphonsine, MAMBERT, Marina, GAYMARD, Alexandre, LINA, Bruno, ROSA‐CALATRAVA, Manuel, BOUSCAMBERT, Maude, TERRIER, Olivier, MEZIANE, Amina, DORIVAL, Céline, BENKEROU, Dehbia, TÉOULÉ, François, LINGAS, Guillaume, LE NAGARD, Hervé, GUEDJ, Jérémie, NEANT, Nadège, ABEL, Laurent, KHAN, Coralie, DESVALLÉE, Mathilde, WIEDEMANN, Aurélie, LEVY, Yves, MOUQUET, Hugo, BEHILILL, Sylvie, van der WERF, Sylvie, ENOUF, Vincent, SEMAILLE, Caroline, dORTENZIO, Eric, CERVANTES‐GONZALEZ, Minerva, PUÉCHAL, Oriane, NORET, Marion, RORIZ, Mélanie, RISPAL, Patrick, REDL, Sarah, LEFEBVRE, Laurent, GRANIER, Pascal, MAULIN, Laurence, JOSEPH, Cédric, MOYET, Julien, LION‐DAOLIO, Sylvie, MAHIEU, Rafael, DUCANCELLE, Alexandra, DUBEE, Vincent, SALLABERRY, Stéphane, MANUEL, Aldric, MACHEDA, Gabriel, MAILLET, Mylène, CHANZY, Bruno, GAGNARD, Jean‐Charles, GIORDANO, Guillermo, MOUTON PERROT, Clara, PESTRE, Vincent, FICKO, Cécile, GOMINET, Marie, BOUSQUET, Aurore, VAUCHY, Charline, BOUILLER, Kévin, PAGADOY, Maïder, MARTY‐QUINTERNET, Solène, LEPILLER, Quentin, LE BRIS, Cyril, THILL, Benoit, CASANOVA, Marie‐Laure, LE FALHER, Georges, OZIOL, Eric, CORDEL, Hugues, DOURNON, Nathalie, BOUCHAUD, Olivier, BRICHLER, Ségolène, NGUYEN, Duc, BELLECAVE, Pantxika, CICCONE, Camille, LAFON, Marie‐Edith, GREFFE, Ségolène, BOUISSE, Camille, SEDILLOT, Nicholas, BOUHOUR, Damien, CHASSIN, Camille, LHER, Erwan, ANSART, Séverine, TROMEUR, Cécile, GUELLEC, Dewi, MERCKX, Antoine, DJOSSOU, Felix, PEIGNE, Vincent, PIEROBON, Carola, CARRET, Marie‐Christine, JEGO, Florence, ISNARD, Margaux, AUCHABIE, Johann, COURTOIS, Roxane, LESENS, Olivier, MARTINOT, Martin, LACOSTE, Marie, ELHARRAR, Brigitte, GARRAIT, Valérie, DELACROIX, Isabelle, MAITRE, Thomas, Baptiste ASSIE, Jean, NYAMANKOLLY, Elsa, Xavier CATHERINE, François, BLOT, Mathieu, MAHY, Sophie, BUISSON, Marielle, PIROTH, Lionel, GUILLOTIN, Florence, DE ROUGEMONT, Alexis, CAMPANA, Valentine, PASQUIER, Jérémie, CABIE, André, BESSIS, Simon, EPAULARD, Olivier, TERZI, Nicolas, PAYEN, Jean‐François, BOUILLET, Laurence, HAMIDFAR, Rebecca, Le MARECHAL, Marion, MACHADO, Moïse, BARRELET, Audrey, BEDOSSA, Alexandra, COLIN, Gwenhaël, DECOURS, Romain, GUIMARD, Thomas, GOUJARD, Cécile, JAUREGUIBERRY, Stéphane, CHERET, Antoine, Sophie RESSEGUIER, Anne, POISSY, Julien, MATHIEU, Daniel, NSEIR, Saad, ENGELMANN, Ilka, REMY, Martine, VUOTTO, Fanny, GACHET, Benoit, FAURE, Karine, BOYER‐BESSEYRE, Marielle, Enagnon, Kazali, LAMBERT, Marc, SCHERPEREEL, Arnaud, FRY, Stéphanie, YELNIK, Cécile, BITKER, Laurent, MEZIDI, Mehdi, YONIS, Hodane, BENECH, Nicolas, PERPOINT, Thomas, CONRAD, Anne, ICARD, Vinca, VALETTE, Martine, THIBERVILLE, Simon‐Djamel, REBAUDET, Stanislas, DUSSOL, Bertrand, DIAMANTIS, Sylvain, CHAKVEATZE, Catherine, FLATEAU, Clara, DINOT, Vincent, GACI, Rostane, OUAMARA, Nadia, ILLES, Hajnal‐Gabriela, GERBAUD MORLAES, Louis, DIMET, Jérôme, LE MOING, Vincent, PANSU, Nathalie, LE BIHAN, Clément, MONTES, Brigitte, Sophie BOUREAU, Anne, ALLAVENA, Clotilde, BOUCHEZ, Sabelline, GUERY, Romain, LE TURNIER, Paul, MEAR‐PASSARD, Cécile, FERRE, Virginie, RAPP, Christophe, DEMONCHY, Elisa, MICHELANGELLI, Céline, RISSO, Karine, LOUBET, Paul, LAVIGNE, Jean‐Phillippe, DE MONTMOLLIN, Etienne, PATRIER, Juliette, Henri WICKY, Paul, LE FEVRE, Lucie, JACQUET, Pierre, BORIE, Raphael, DOSSIER, Antoine, LUTON, Dominique, ISERNIA, Valentina, LE GAC, Sylvie, AZOULAY, Cécile, CARLIER, Nicolas, LUONG, Liem, LACHATRE, Marie, LAUNAY, Odile, KERROUMI, Younes, MEYSSONNIER, Vanina, DIEHL, Jean‐Luc, HULOT, Jean‐Sébastien, CHOLLEY, Bernard, ARLET, Jean‐Benoît, SANCHEZ, Olivier, MANDA, Victoria, AZEMAR, Laurène, CASTOR‐ALEXANDRE, Guylaine, LACOMBE, Karine, CHIARABINI, Thibault, LEFEBVRE, Bénédicte, MORAND‐JOUBERT, Laurence, FOFANA, Djeneba, SCHNURIGER, Aurélie, DE CASTRO, Nathalie, DELAUGERRE, Constance, CHAIX, Marie‐Laure, CHAS, Julie, GABORIEAU, Valérie, LE COUSTUMIER, Eve, PICARD, Walter, ZABBE, Jean‐Benoît, PEELMAN, Florent, SOUM, Edouard, AUMAÎTRE, Hugues, CURLIER, Elodie, OUISSA, Rachida, FABRE, Isabelle, RAMMAERT, Blandine, SAIDANI, Nadia, BANI‐SADR, Firouzé, HENTZIEN, Maxime, NGUYEN, Yohan, ROMARU, Juliette, DIDIER, Kévin, ENDERLE, Isabelle, THIBAULT, Vincent, LAINE, Fabrice, LESOUHAITIER, Matthieu, REVEST, Matthieu, TATTEVIN, Pierre, PLANTIER, Jean‐Christophe, LEMEE, Véronique, FERRAND DEVOUGE, Eglantine, ALEXANDRE, Kévin, ARTAUD‐MACCARI, Elise, ALLOU, Nathalie, LAGRANGE, Marie, JABOT, Julien, ROZE, Benoît, BREGEAUD, Delphine, AIT TAMLIHAT, Younes, HACHEMI, Ali, SALVATOR, Hélène, FOURN, Erwan, ZUCMAN, David, DELAVEUVE, Eric, JAUD‐FISCHER, Coline, DUNAND, Paul, BISSUEL, François, DELAVIGNE, Karen, PIEL‐JULIAN, Marie, DELOBEL, Pierre, SARTON, Benjamine, RAFIQ, Marie, MARTIN‐BLONDEL, Guillaume, GUILLEMINAULT, Laurent, MURRIS, Marlène, SOMMET, Agnès, SENNEVILLE, Eric, ROBINEAU, Olivier, MEYBECK, Agnès, GAROT, Denis, PLANTIER, Laurent, GISSOT, Valérie, MARLET, Julien, STEFIC, Karl, GAUDY‐GRAFFIN, Catherine, BARIN, Francis, LEMAIGNEN, Adrien, CORVAISIER, Grégory, LARIVIERE, Delphine, LANGELOT‐RICHARD, Marie, BOTELHO‐NEVERS, Elisabeth, GAGNEUX‐BRUNON, Amandine, TROUILLON, Tiffany, BOURLET, Thomas, PILLET, Sylvie, POZZETTO, Bruno, KIMMOUM, Antoine, LEVY, Bruno, MATTEI, Mathieu, GOEHRINGER, François, RABAUD, Christian, BEVILACQUA, Sibylle, LEFEVRE, Benjamin, GUILLAUMOT, Anne, VENARD, Véronique, JEULIN, Hélène, SCHVOERER, Evelyne, HARTARD, Cédric, CARAUX PAZ, Pauline, RICHIER, Laurent, EL SANHARAWI, Mohamed, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, ANRS France Recherche Nord & sud Sida-hiv hépatites, France REcherche Nord & sud Sida-hiv Hépatites (FRENSH), CHU Amiens-Picardie, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, French COVID cohort study group, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre d'Investigation Clinique - Innovation Technologique de Lille - CIC 1403 - CIC 9301 (CIC Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), CHU Rouen, Normandie Université (NU), and The Alliance for International Medical Action [Dakar, Sénégal] (ONG ALIMA)

Subjects
Adult, Male, medicine.medical_specialty, Multivariate analysis, Adolescent, prospective cohort, SARS‐CoV‐2, Cohort Studies, Young Adult, coronavirus disease 2019, 03 medical and health sciences, Patient Admission, 0302 clinical medicine, Risk Factors, Virology, Internal medicine, Diabetes mellitus, emerging infection diseases, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Research Articles, Aged, Aged, 80 and over, SARS-CoV-2, Proportional hazards model, business.industry, Hazard ratio, Age Factors, COVID-19, Middle Aged, Viral Load, medicine.disease, Obesity, Confidence interval, Hospitalization, Infectious Diseases, Female, 030211 gastroenterology & hepatology, France, business, Viral load, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Article
Abstract

Little is known on the association between clinical factors and coronavirus disease 2019 (COVID‐19) more than 15 days after diagnosis. We conducted a multicentric prospective cohort of COVID‐19 hospitalized patients to describe clinical, biological, and virological characteristics at hospital admission and over time, according to mortality up to Day 60 after admission. For the analysis of risk factors of survival, analyses assessing associations between mortality and demographic characteristics or comorbidities were performed using a Cox regression model. Between January 24 and March 15, 2020, 246 patients with reverse‐transcriptase polymerase chain reactions virologically confirmed COVID‐19 were enrolled. In multivariate analysis, mortality at Day 60 (n = 42 patients, 17.1% [95% confidence interval, 12.6–22.4]) was associated with older age (adjusted hazard ratio [aHR] for age ≥ 65 years: 5.22 [2.56–10.63, p, Highlights Older age, male gender, chronic pulmonary disease (not asthma), obesity, and diabetes were associated with mortality in COVID‐19 hospitalized patients. Viral load at admission decreased with the time since symptom onset, with an association with mortality adjusted on clinical risk factors.

Published
2020
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35. Systematic review: Diagnostics, management and outcome of fractures of the posterior process of the talus

Author

Olivier Wijers, Tim Schepers, Esmee W M Engelmann, and Jelle J. Posthuma

Subjects
medicine.medical_specialty, Joint Dislocations, Cochrane Library, Delayed diagnosis, Trauma, Talus, Fracture Fixation, Internal, Fractures, Bone, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Shepherd fracture, Complication rate, Joint dislocation, Foot injury, General Environmental Science, 030222 orthopedics, Cedell fracture, business.industry, Chronic pain, Talus body, 030208 emergency & critical care medicine, medicine.disease, Level of evidence: IV, Surgery, Treatment Outcome, Extremity fractures, General Earth and Planetary Sciences, Posterior process fracture, Joint Diseases, Outcome data, business, Stieda's process
Abstract

Background: Fractures of the posterior process of the talus are rare and frequently overlooked, possibly leading to pseudo-arthrosis and chronic pain. To gain more insight into the diagnosis, treatment and outcome of fractures of the posterior process of the talus (PPTF), a systematic review of the current literature was performed to provide recommendations for the management of PPTF. Methods: A literature search in the electronic databases of PubMed, EMbase, Google Scholar and Cochrane library was performed in January 2020 to identify all clinical studies on PPTF with more than three patients. Amongst other variables, the type of study, number of patients, mechanism of injury, type of fracture (anatomy), imaging modality, treatment, postoperative protocol, outcomes, complications and duration of follow-up were noted for systematic analysis of the available evidence, adherent to the PRISMA guidelines. Results: Seven original studies were included with a total of 66 patients. More than one third of patients presented with a (sub)talar joint dislocation (n = 25, 37.9%) and 51.5% sustained associated ipsilateral lower extremity fractures (n = 34). Delayed diagnosis occurred in 36.4% of patients (n = 24). Out of 48 patients with outcome data available, 41.7% (n = 20) reported impaired function. In the non-operative group, 64.7% (n = 11) had impaired functional outcome, compared to 33.3% (n = 6) in the ORIF group, and 30.8% (n = 4) in the fragment excision group (p < 0.001). One third of the patients developed one or more complications (n = 25, 37.9%), mostly found in the non-operatively treated group (73.7%, n = 14) compared to ORIF (25.0%, n = 8, p < 0.001). Conclusion: Early recognition and timely treatment is warranted in order to achieve pre-injury functional outcome and reduce morbidity. Given the significantly higher complication rate and lower return to the previous level of functionality reported after non-operative treatment, ORIF is recommended if there is (even minimal) displacement, articular involvement or if the fracture extends into the talus body.

Published
2020
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36. Normal liver stiffness and influencing factors in healthy children: An individual participant data meta‐analysis

Author

Marion Rowland, Mohammad Hassan Murad, Voranush Chongsrisawat, David Cassiman, Muhammad Rehan Khan, Imeke Goldschmidt, Ulrike Teufel-Schäfer, Katryn N. Furuya, Samir Haffar, Larry D. Prokop, Peter Lewindon, Anders Batman Mjelle, Panida Swangsak, Ulrich Baumann, Yuki Cho, Zhen Wang, Peter Witters, Kathleen E. Corey, Ioana Ciuca, Fateh Bazerbachi, Daisuke Tokuhara, Guido Engelmann, Darrick K. Li, and Grant A. Ramm

Subjects
Liver Cirrhosis, medicine.medical_specialty, animal structures, Adolescent, Sedation, Reference range, Subgroup analysis, 03 medical and health sciences, 0302 clinical medicine, Reference Values, Internal medicine, Bayesian multivariate linear regression, medicine, Humans, Child, Hepatology, business.industry, medicine.disease, Confidence interval, Fatty Liver, Liver, 030220 oncology & carcinogenesis, Meta-analysis, Elasticity Imaging Techniques, 030211 gastroenterology & hepatology, Steatosis, medicine.symptom, Transient elastography, business
Abstract

BACKGROUND & AIMS Although transient elastography (TE) is used to determine liver stiffness as a surrogate to hepatic fibrosis, the normal range in children is not well defined. We performed a systematic review and individual participant data (IPD) meta-analysis to determine the range of liver stiffness in healthy children and evaluate the influence of important biological parameters. METHODS We pooled data from 10 studies that examined healthy children using TE. We divided 1702 children into two groups: ≥3 years (older group) and

Published
2020
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37. Vasopressin and post-traumatic stress disorder

Author

István Barna, Bibiána Török, Eszter Sipos, Dóra Zelena, and Mario Engelmann

Subjects
Receptors, Vasopressin, endocrine system, Cell signaling, Vasopressin, Arginine, Vasopressins, Physiology, Stress Disorders, Post-Traumatic, 03 medical and health sciences, Behavioral Neuroscience, 0302 clinical medicine, medicine, Animals, Humans, Receptor, Endocrine and Autonomic Systems, business.industry, Traumatic stress, Rats, Brattleboro, Hypotonia, Rats, 030227 psychiatry, Psychiatry and Mental health, Neuropsychology and Physiological Psychology, medicine.symptom, business, Neuroscience, Antidiuretic Hormone Receptor Antagonists, Stress, Psychological, hormones, hormone substitutes, and hormone antagonists, 030217 neurology & neurosurgery, Vasoconstriction, Hormone
Abstract

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition with a wide range of behavioral disturbances and serious consequences for both patient and society. One of the main reasons for unsuccessful therapies is insufficient knowledge about its underlying pathomechanism. In the search for centrally signaling molecules that might be relevant to the development of PTSD we focus here on arginine vasopressin (AVP). So far AVP has not been strongly implicated in PTSD, but different lines of evidence suggest a possible impact of its signaling in all clusters of PTSD symptomatology. More specifically, in laboratory rodents, AVP agonists affect behavior in a PTSD-like manner, while significant reduction of AVP signaling in the brain e.g. in AVP-deficient Brattleboro rats, ameliorated defined behavioral parameters that can be linked to PTSD symptoms. Different animal models of PTSD also show alterations in the AVP signaling in distinct brain areas. However, pharmacological treatment targeting central AVP receptors via systemic routes is hampered by possible side effects that are linked to the peripheral action of AVP as a hormone. Indeed, the V1a receptor, the most common receptor subtype in the brain, is implicated in vasoconstriction. Thus, systemic treatment with V1a receptor antagonists would be implicated in hypotonia. This implies that novel treatment concepts are needed to target AVP receptors not only at brain level but also in distinct brain areas, to offer alternative treatments for PTSD.

Published
2020
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38. Effects of electrostimulation therapy in facial nerve palsy

Author

Lukas Prantl, Andreas Kehrer, Alexandra Anker, Laura Sommerauer, Simon Engelmann, and Marc Ruewe

Subjects
medicine.medical_specialty, RD1-811, Case Report, Schwannoma, Functional disorder, 03 medical and health sciences, Craniofacial, 0302 clinical medicine, Paralysis, medicine, Neurotization, 030223 otorhinolaryngology, Pediatric/Craniomaxillofacial/Head & Neck, Palsy, business.industry, medicine.disease, Facial nerve, Facial paralysis, Surgery, Nerve Transfer, Electrical stimulation, Cross face nerve graft, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Facial palsy (FP) is a functional disorder of the facial nerve involving paralysis of the mimic muscles. According to the principle “time is muscle,” early surgical treatment is tremendously important for preserving the mimic musculature if there are no signs of nerve function recovery. In a 49-year-old female patient, even 19 months after onset of FP, successful neurotization was still possible by a V-to-VII nerve transfer and cross-face nerve grafting. Our patient suffered from complete FP after vestibular schwannoma surgery. With continuous application of electrostimulation (ES) therapy, the patient was able to bridge the period between the first onset of FP and neurotization surgery. The significance of ES for mimic musculature preservation in FP patients has not yet been fully clarified. More attention should be paid to this form of therapy in order to preserve the facial musculature, and its benefits should be evaluated in further prospective clinical studies.

Published
2020

39. Quality assessment of patient information on orthognathic surgery on the internet

Author

Carmen Fischer, Emeka Nkenke, and Johannes Engelmann

Subjects
Oral, medicine.medical_specialty, medicine.medical_treatment, media_common.quotation_subject, Orthognathic surgery, Article, 03 medical and health sciences, 0302 clinical medicine, Patient information, medicine, Humans, Quality (business), Medical physics, Evaluation, media_common, Internet, Consumer Health Information, Quality assessment, business.industry, Orthognathic Surgery, Information quality, 030206 dentistry, EQIP, Identification (information), Search terms, Health information, Otorhinolaryngology, 030220 oncology & carcinogenesis, Surgery, The Internet, Oral Surgery, business
Abstract

Objective The aim of this study was to assess the quality of online information for patients on orthognathic surgery. Materials and methods A selection of search terms specific for orthognathic surgery was chosen and 150 websites were identified using the Internet search engines Google, Yahoo and Bing. Irrelevant websites were excluded. The remaining websites were assessed with a modified Ensuring Quality Information for Patients (EQIP) tool. EQIP evaluates the quality of medical patient information by measuring the three key aspects of content, structure, and identification data. Results 48 relevant websites were identified. EQIP values ranged between 2 and 28 (median 13.65). While 37 of the 48 websites described details of the surgical procedures, only 13 mentioned possible risks and complications of the surgery. No differences were found between the websites of private practices, dentists and public hospitals, universities, or others (p = 0.66). Websites found by Google had a significantly lower EQIP score compared with Yahoo and Bing (11.12 vs. 16.60 for Yahoo and 16.23 for Bing; p = 0.012). The better the rank of the website, the higher the EQIP score (r = −0.411, p = 0.004). Conclusions The results of this study reflected a large variation of quality of information on orthognathic surgery on the Internet. Therefore, surgeons must be aware that they might be confronted with unrealistic expectations of patients, who may underestimate the potential risks and drawbacks of orthognathic surgery.

Published
2020
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40. Screening for New Markers to Assess Thyroid Hormone Action by OMICs Analysis of Human Samples

Author

Nele Friedrich, Maik Pietzner, Georg Homuth, Uwe Völker, Georg Brabant, Henri Wallaschofski, Beatrice Engelmann, and Dagmar Führer

Subjects
0301 basic medicine, endocrine system, Proteome, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Population, Medizin, 030209 endocrinology & metabolism, Bioinformatics, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal Medicine, medicine, Central hypothyroidism, Humans, education, education.field_of_study, business.industry, Pituitary tumors, Thyroid, General Medicine, medicine.disease, Omics, Thyroid Diseases, Thyroid hormone resistance, 030104 developmental biology, medicine.anatomical_structure, Metabolome, Thyroid function, Transcriptome, business, Biomarkers, Hormone
Abstract

Determination of the levels of thyroid-stimulating hormone (TSH) and free thyroid hormones (fTHs) is crucial for assessing thyroid function. However, as a result of inter-individual genetic variability and different environmental factors individual set points exist for TSH and fTHs and display considerable variation. Furthermore, under specific pathophysiological conditions like central hypothyroidism, TSH secreting pituitary tumors, or thyroid hormone resistance the established markers TSH and fTH fail to reliably predict thyroid function and adequate supply of TH to peripheral organs. Even in case of overt hyper- and hypothyroidism circulating fTH concentrations do not correlate with clinical symptoms. Therefore, there is a clear need for novel, more specific biomarkers to diagnose and monitor thyroid function. OMICs screening approaches allow parallel profiling of hundreds to thousands of molecules and thus comprehensive monitoring of molecular alterations in tissues and body fluids that might be associated with changes in thyroid function. These techniques thus constitute promising tools for the identification of urgently needed novel biomarkers. This mini review summarizes the findings of OMICs studies in thyroid research with a particular focus on population-based and patient studies as well as interventional approaches investigating the effects of thyroid hormone administration.

Published
2020
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41. Into the Deep - AI and Total Pathology

Author

Lukas Engelmann

Subjects
Cultural Studies, Health (social science), Sociology and Political Science, business.industry, 05 social sciences, 0507 social and economic geography, Biomedical Engineering, Library science, 050905 science studies, History and Philosophy of Science, Health care, Sociology, 0509 other social sciences, business, 050703 geography, Biotechnology
Abstract

One of the first images you would have seen when opening Verily.com’s website in 2017, just after Google had collapsed its lifestyle and health projects under this new single roof, was a colourful ...

Published
2020
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42. There Is a Great Future in Plastics: Personalized Approach to the Management of Hilar Cholangiocarcinoma Using a 3-D-Printed Liver Model

Author

Quirino Lai, Paolo Gaudenzi, Simone Novelli, Gianluca Mennini, Zoe Larghi Laureiro, Raj Mookarje, Vito D'Andrea, Franco Marinozzi, Massimo Rossi, Dimitri A. Raptis, Rajiv Jalan, and Cornelius Engelmann

Subjects
Adult, Models, Anatomic, medicine.medical_specialty, Physiology, Portal vein, Surgical planning, Klatskin tumor, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Precision Medicine, Thrombus, 3-D printing, Thrombosis, business.industry, Gastroenterology, Hepatology, medicine.disease, Surgical training, Bile Duct Neoplasms, 030220 oncology & carcinogenesis, Printing, Three-Dimensional, Main portal vein, Female, 030211 gastroenterology & hepatology, Radiology, business, Vascular Surgical Procedures
Abstract

In recent years, three-dimensional (3-D) printing technology has become a standard tool that is used in several medical applications such as education, surgical training simulation and planning, and doctor-patient communication. Although liver surgery is ideally complemented by the use of preoperative 3-D-printed models, only a few publications have addressed this topic. We report the case of a 29-year-old Caucasian woman admitted for a Klatskin tumor infiltrating the right portal vein requiring surgery that required complex vascular reconstruction. A life-sized liver model with colorful plastic vessels and realistic looking tumor was created with the aim of planning an optimal surgical approach. According to the 3-D model, we performed a right hepatic trisectionectomy, also removing enbloc the tract of portal vein encased by the tumor and the neoplastic thrombus, followed by a complex vascular reconstruction between the main portal vein and the left portal branch. After 22 months of follow-up, the patient was alive and continuing chemotherapy. The use of the 3-D models in liver surgery helps clarify several useful preoperative issues. The accuracy of the model regarding anatomical findings was high. In the case of complex vascular reconstruction strategies, rational use of 3-D printing technology should be implemented.

Published
2020
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43. Osteosarcoma in a Dachshund: cytological and histopathological aspects

Author

D. T. O. Mayer, Rafael A. Fighera, Camila Benaduce Emanuelli Mello, F. G. Roth, R. D. Mazaro, Cinthia Melazzo de Andrade, Ana Martiele Engelmann, and Cássia B. da Silva

Subjects
medicine.medical_specialty, Chemotherapy, Hematology, 040301 veterinary sciences, business.industry, Dachshund, medicine.medical_treatment, 04 agricultural and veterinary sciences, Malignancy, medicine.disease, Pathology and Forensic Medicine, 0403 veterinary science, Primary bone, Internal medicine, medicine, Osteosarcoma, Doxorubicin, Radiology, Anatomy, business, Histopathological aspects, medicine.drug
Abstract

Malignant primary bone neoplasms are characterized by high malignancy and metastatic capacity, commonly affecting dogs of large or giant breeds. The prognosis is reserved to unfavorable for the patients. This paper describes a case of osteosarcoma in the left pelvic limb of a Dachshund, diagnosed by fine-needle aspiration cytology and confirmed by histopathological evaluation. The patient underwent limb amputation and doxorubicin chemotherapy; however, the dog died. This report alerts clinicians to the occurrence of osteosarcoma in small animals and demonstrates the importance of fine-needle aspiration cytology as a tool in the diagnosis of bone neoplasms.

Published
2020
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44. Conditional deletion of Nedd4-2 in lung epithelial cells causes progressive pulmonary fibrosis in adult mice

Author

Dmytro Dvornikov, Jan Hegermann, Simon G. Fraumann, Daniela Rotin, Surafel Mulugeta, Felix Herth, Michael Kreuter, Julia Duerr, Hiroshi Kawabe, Magdalena Szczygiel, Ayça Seyhan Agircan, Ursula Klingmüller, Clemens Kreutz, Mark O. Wielpütz, Dominik Leitz, Matthias Ochs, Marcus A. Mall, Theresa A. Engelmann, Philip Konietzke, Piotr K. Zadora, Thomas Muley, Michael F. Beers, and Lars Knudsen

Subjects
Proteomics, 0301 basic medicine, Pathology, Ubiquitylation, Biopsy, Nedd4 Ubiquitin Protein Ligases, General Physics and Astronomy, Pathogenesis, Mice, Idiopathic pulmonary fibrosis, 0302 clinical medicine, Fibrosis, Pulmonary fibrosis, lcsh:Science, Lung, Mice, Knockout, Multidisciplinary, Interstitial lung disease, Pirfenidone, Middle Aged, respiratory system, Mucin-5B, humanities, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, medicine.drug, Adult, medicine.medical_specialty, Pyridones, Science, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, medicine, Animals, Humans, Epithelial Sodium Channels, Aged, NEDD4L, Respiratory tract diseases, business.industry, Ubiquitination, Epithelial Cells, General Chemistry, medicine.disease, Idiopathic Pulmonary Fibrosis, respiratory tract diseases, Disease Models, Animal, 030104 developmental biology, lcsh:Q, business
Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease characterized by patchy scarring of the distal lung with limited therapeutic options and poor prognosis. Here, we show that conditional deletion of the ubiquitin ligase Nedd4-2 (Nedd4l) in lung epithelial cells in adult mice produces chronic lung disease sharing key features with IPF including progressive fibrosis and bronchiolization with increased expression of Muc5b in peripheral airways, honeycombing and characteristic alterations in the lung proteome. NEDD4-2 is implicated in the regulation of the epithelial Na+ channel critical for proper airway surface hydration and mucus clearance and the regulation of TGFβ signaling, which promotes fibrotic remodeling. Our data support a role of mucociliary dysfunction and aberrant epithelial pro-fibrotic response in the multifactorial disease pathogenesis. Further, treatment with the anti-fibrotic drug pirfenidone reduced pulmonary fibrosis in this model. This model may therefore aid studies of the pathogenesis and therapy of IPF., Idiopathic pulmonary fibrosis (IPF) is a devastating disease with poor prognosis. Here, the authors show that deficiency of the E3 ubiqutin-protein ligase Nedd4-2 in airway epithelial cells causes IPF-like disease in adult mice. This model may aid studies of the pathogenesis and therapy of IPF.

Published
2020

45. Advances in Interfacing Optical Fibers to Nanophotonic Waveguides Via Mechanically Compliant Polymer Waveguides

Author

Shotaro Takenobu, Richard Langlois, Tymon Barwicz, Bo Peng, Swetha Kamlapurkar, Sebastian Engelmann, Paul Fortier, Nicolas Boyer, Alexander Janta-Polczynski, Yoichi Taira, Hidetoshi Numata, Katsuki Suematsu, and Kengo Watanabe

Subjects
Materials science, Silicon photonics, Optical fiber, business.industry, Bandwidth (signal processing), Nanophotonics, Physics::Optics, 02 engineering and technology, Polarization (waves), Atomic and Molecular Physics, and Optics, law.invention, Cable gland, 020210 optoelectronics & photonics, Interfacing, law, 0202 electrical engineering, electronic engineering, information engineering, Optoelectronics, Electrical and Electronic Engineering, Photonics, business
Abstract

Interfacing standard optical fibers with high index-contrast photonic waveguides remains a substantial challenge restricting the cost-efficiency and scalability of silicon photonic devices. To address this, we have proposed a mechanically compliant polymer interface, formed of a standard fiber connection and a flexible ribbon with lithographically defined polymer waveguides. Self-aligned mechanical assembly and optical mode evolution designs are employed for low cost and large spectral bandwidth. In this paper, we review our progress leading to the full demonstration of this concept with −1.8 dB peak transmission from a plugged-in standard fiber connector to Si wire waveguides. This with 0.7 dB roll-off on a 100 nm bandwidth and all polarization. We present a comprehensive analysis of loss sources and discuss intermediate results, self-alignment accuracy, and reliability.

Published
2020
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46. To Peel or Not to Peel: Pars Plana Vitrectomy with Macular Membrane Peel in Eyes with Abnormalities of Vitreomacular Interface and Coexisting Dry Age-Related Macular Degeneration

Author

Katrin Engelmann and Olga Furashova

Subjects
Pars plana, medicine.medical_specialty, Visual acuity, genetic structures, ILM, Eye disease, medicine.medical_treatment, Vitrectomy, choroidal neovascularization, 03 medical and health sciences, 0302 clinical medicine, Ophthalmology, medicine, Full-thickness macular hole, age-related macular degeneration, Original Research, pars plana vitrectomy, business.industry, Clinical Ophthalmology, Macular degeneration, medicine.disease, eye diseases, medicine.anatomical_structure, Choroidal neovascularization, epiretinal membrane peeling, 030221 ophthalmology & optometry, macular membrane peel, sense organs, medicine.symptom, Epiretinal membrane, business, 030217 neurology & neurosurgery
Abstract

Olga Furashova, Katrin Engelmann Department of Ophthalmology, Klinikum Chemnitz gGmbH, Chemnitz, GermanyCorrespondence: Olga FurashovaDepartment of Ophthalmology, Klinikum Chemnitz gGmbH, Flemmingstrasse 2, Chemnitz 09116, GermanyTel +49 371 333 33230Fax +49 371 333 33223Email fur.olga@gmail.comPurpose: To evaluate the outcome of macular surgery with ILM- and epiretinal membrane peel associated with significant dry age-related macular degeneration (AMD) as defined by the Age-Related Eye Disease Study (AREDS).Patients and Methods: Institutional. Retrospective case-control study. A total of 42 pseudophacic eyes of 39 patients (7 with full thickness macular hole and 35 with epiretinal membrane) with coexisting dry AMD underwent pars plana vitrectomy (PPV) with internal limiting membrane (ILM) and epiretinal membrane peel. Preoperative and postoperative data including best corrected visual acuity (BCVA), AMD grade according to AREDS, central retinal thickness (CRT), development of choroidal neovascularization (CNV), and central retinal atrophy have been evaluated. Twenty-eight fellow eyes with dry AMD of the included 39 patients served as a control group.Results: A significant improvement in the visual acuity could be observed after surgery (initial BCVA 0.47± 0.31 logarithm of the minimal angle of resolution (logMAR) vs 0.33± 0.29logMAR 9 months postoperatively; p=0.006). CRT decreased significantly after surgery (p< 0.001). In the surgery group, there were 4 eyes (9.5%) with CNV and 1 eye (2.5%) with new central retinal atrophy development after surgery. All these eyes had preoperative AREDS 3 (4 eyes) or AREDS 4 (1 eye) AMD category. In the control group, there was 1 eye (4%) with CNV and 4 eyes (14%) with new central retinal atrophy development during the follow-up of 9 months. These eyes had initially AREDS 2 (1 eye), AREDS 3 (3 eyes) or AREDS 4 (1 eye) AMD category.Conclusion: Eyes with dry AMD of AREDS 3 and AREDS 4 with coexisting VMI abnormalities improve significantly after PPV with membrane peel. While there is a higher risk of CNV development after surgery (9.5%) in these eyes, the vitrectomy does not seem to accelerate central retinal atrophy progression compared to the fellow eyes course.Keywords: macular membrane peel, choroidal neovascularization, pars plana vitrectomy, age-related macular degeneration, ILM, epiretinal membrane peeling

Published
2020
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47. Dekompensierte Leberzirrhose und akut-auf-chronisches Leberversagen

Author

C. Engelmann and Frank Tacke

Subjects
Gynecology, 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, business.industry, 030220 oncology & carcinogenesis, Gastroenterology, medicine, 030211 gastroenterology & hepatology, business
Abstract

Patienten mit Leberzirrhose, die auf der Intensivstation behandelt werden, haben eine hohe Letalitat. Man unterscheidet die dekompensierte Leberzirrhose, d. h. typische Komplikationen der Zirrhose, wie Osophagusvarizenblutung, hepatische Enzephalopathie, hepatorenales Syndrom oder Aszites, vom akut-auf-chronischen Leberversagen (ACLF), bei dem begleitend zur vorbestehenden chronischen Lebererkrankung ein oder mehrere Organversagen vorliegen. In beiden Fallen ist ein strukturiertes intensivmedizinisches Management zur zielgerechten Behandlung der Ursachen der Dekompensation (z. B. Blutungen, Infektionen, Exsikkose, Medikamente) und der begleitenden Organversagen (z. B. Nierenversagen, Enzephalopathie) essenziell. Fur Organversagen sind Kriterien definiert, die die Diagnose eines ACLF ermoglichen. Eine besondere Bedeutung kommt der schnellen und adaquaten (antibiotischen und antimykotischen) Infekttherapie zu. Fur typische Komplikationen der Leberzirrhose, wie Nierenversagen/hepatorenales Syndrom, hepatische Enzephalopathie, Aszites oder Varizenblutungen, existieren klare Behandlungspfade. Bei ACLF oder dekompensierter Leberzirrhose sollte immer die Moglichkeit einer Lebertransplantation bedacht und im interdisziplinaren Team diskutiert werden. Neue Behandlungsansatze beim ACLF adressieren in klinischen Studien Mechanismen der Inflammation, Immunantwort und Regeneration.

Published
2020
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48. Plasma-driven catalysis: green ammonia synthesis with intermittent electricity

Author

Annemie Bogaerts, Kevin Hendrik Reindert Rouwenhorst, Leon Lefferts, Yannick Engelmann, Rolf Sybren Postma, Kevin van ’t Veer, and Catalytic Processes and Materials

Subjects
Energy carrier, business.industry, Fossil fuel, Pollution, Catalysis, Renewable energy, Ammonia production, Chemistry, Ammonia, chemistry.chemical_compound, chemistry, Environmental Chemistry, Environmental science, Electricity, Biochemical engineering, business, Engineering sciences. Technology, Efficient energy use
Abstract

Ammonia is one of the most produced chemicals, mainly synthesized from fossil fuels for fertilizer applications. Furthermore, ammonia may be one of the energy carriers of the future, when it is produced from renewable electricity. This has spurred research on alternative technologies for green ammonia production. Research on plasma-driven ammonia synthesis has recently gained traction in academic literature. In the current review, we summarize the literature on plasma-driven ammonia synthesis. We distinguish between mechanisms for ammonia synthesis in the presence of a plasma, with and without a catalyst, for different plasma conditions. Strategies for catalyst design are discussed, as well as the current understanding regarding the potential plasma-catalyst synergies as function of the plasma conditions and their implications on energy efficiency. Finally, we discuss the limitations in currently reported models and experiments, as an outlook for research opportunities for further unravelling the complexities of plasma-catalytic ammonia synthesis, in order to bridge the gap between the currently reported models and experimental results.

Published
2020
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49. VNF Availability and SFC Sizing Model for Service Provider Networks

Author

Sidharth Sharma, Admela Jukan, Ashwin Gumaste, and Anna Engelmann

Subjects
VNF, General Computer Science, business.industry, Computer science, General Engineering, 020206 networking & telecommunications, Provisioning, Availability, 02 engineering and technology, Service provider, service function chaining, Network planning and design, 020210 optoelectronics & photonics, Robustness (computer science), 0202 electrical engineering, electronic engineering, information engineering, Redundancy (engineering), General Materials Science, lcsh:Electrical engineering. Electronics. Nuclear engineering, business, Heuristics, Virtual network, lcsh:TK1-9971, Computer network
Abstract

This paper considers service provider network design with a view of meeting application availability. Our primary goal is to design a service provider network using disparate network components and low-availability Virtual Network Functions (VNFs) while achieving high-availability Service Function Chains (SFCs). To this end, we attempt to answer the questions as to how much redundancy, and what type of redundancy should be incorporated in the network. Initially, we model a state-of-the-art provider architecture that is spread across the access, metro-core and backbone networks with associated discrete components such as switches, routers, optical equipment and data-centers. Our network design model leads to computing the amount of over-the-top (OTT) services that can be provisioned over a given network while achieving a particular availability. To this end, we formulate a constrained optimization model whose objective is profit maximization subject to availability measures that OTT services demand. We provide constraints of robustness that facilitate traffic churn. Four heuristics are also proposed with objectives that consider the breadth of the three key impacting parameters: VNF licensing cost, server utilization and delay optimization and the case for dynamic traffic. A simulation model presents comparative data for efficiency, latency and server utilization as well as validates our optimization model. The results stress the importance of an efficient optimization model in planning the network, as well as planning VNF placement ahead in time.

Published
2020

50. Prognostic Role of Liver Biopsy in Patients With Severe Indeterminate Acute Hepatitis

Author

Rajesh Kumar, Cornelius Engelmann, Catarina Araujo, Rajiv Jalan, Alberto Quaglia, Su Lin, Andrew M. Hall, Alexandra Phillips, and Mohsin Hassan

Subjects
medicine.medical_specialty, medicine.medical_treatment, Biopsy, Histopathology, Liver transplantation, Single Center, Gastroenterology, Severity of Illness Index, Hepatitis, End Stage Liver Disease, Liver disease, Necrosis, Model for End-Stage Liver Disease, Interquartile range, Internal medicine, medicine, Humans, Hepatology, medicine.diagnostic_test, business.industry, Multiplex Immunofluorescence, ANPAT, medicine.disease, Prognosis, Liver biopsy, Acute Disease, business, Rare disease
Abstract

Background and aims: Severe indeterminate acute hepatitis (sIAH) is a poorly understood rare disease with no specific therapy. This study aims to define the clinicopathological characteristics of sIAH and the role of liver biopsy in determining prognosis. Methods: Patients with sIAH admitted to a single center between 2010 and 2019 were included. Histopathological patterns of liver biopsies were reviewed by 2 histopathologists, and key findings further were specified by multiplex immunofluorescence. Patients that died or underwent liver transplantation were analyzed as nonsurvivors. Results: Of 294 patients with acute hepatitis, 43 with sIAH were included. Seventeen (39.5%) underwent liver transplantation and 7 (16.2%) died within 3 months. Multilobular necrosis was the predominant histopathological feature, being significantly more frequent in nonsurvivors (62.5% vs 21.1%; P = .016). Necrotic areas showed low HNF4α and Ki67 expression but high expression of CK19 and cell death markers identifying areas of severe tissue injury and inadequate regenerative response. Patients with multilobular necrosis had higher international normalized ratio, Model for End-Stage Liver Disease, and Model for End-Stage Liver Disease-Sodium scores compared with those without (P values for all markers

Published
2022

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