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1. ESC guidance for the diagnosis and management of cardiovascular disease during the COVID-19 pandemic: part 1—epidemiology, pathophysiology, and diagnosis

Author: Baigent, Colin, Windecker, Stephan, Andreini, Daniele, Arbelo, Elena, Barbato, Emanuele, Bartorelli, Antonio, Baumbach, Andreas, Behr, Elijah, Berti, Sergio, Bueno, Héctor, Capodanno, Davide, Cappato, Riccardo, Chieffo, Alaide, Collet, Jean-Philippe, Cuisset, Thomas, de Simone, Giovanni, Delgado, Victoria, Dendale, Paul, Dudek, Dariusz, Edvardsen, Thor, Elvan, Arif, González-Juanatey, José, Gori, Mauro, Grobbee, Diederick, Guzik, Tomasz, Halvorsen, Sigrun, Haude, Michael, Heidbuchel, Hein, Hindricks, Gerhard, Ibanez, Borja, Karam, Nicole, Katus, Hugo, Klok, Fredrikus, Konstantinides, Stavros, Landmesser, Ulf, Leclercq, Christophe, Leonardi, Sergio, Lettino, Maddalena, Marenzi, Giancarlo, Mauri, Josepa, Metra, Marco, Morici, Nuccia, Mueller, Christian, Petronio, Anna Sonia, Polovina, Marija, Potpara, Tatjana, Praz, Fabien, Prendergast, Bernard, Prescott, Eva, Price, Susanna, Pruszczyk, Piotr, Rodríguez-Leor, Oriol, Roffi, Marco, Romaguera, Rafael, Rosenkranz, Stephan, Sarkozy, Andrea, Scherrenberg, Martijn, Seferovic, Petar, Senni, Michele, Spera, Francesco, Stefanini, Giulio, Thiele, Holger, Tomasoni, Daniela, Torracca, Lucia, Touyz, Rhian, Wilde, Arthur, Williams, Bryan, Bern University Hospital [Berne] (Inselspital), Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano = University of Milan (UNIMI)-Università degli Studi di Milano = University of Milan (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), 'Federico II' University of Naples Medical School, St George's, University of London, Fondazione Toscana Gabriele Monasterio, Hospital Universitario 12 de Octubre [Madrid], Centro Nacional de Investigaciones Cardiovasculares Carlos III [Madrid, Spain] (CNIC), Instituto de Salud Carlos III [Madrid] (ISC), University of Catania [Italy], IRCCS San Raffaele Scientific Institute [Milan, Italie], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital de la Timone [CHU - APHM] (TIMONE), Leiden University Medical Center (LUMC), Universiteit Leiden, Hasselt University (UHasselt), Jessa Ziekenhuis [Hasselt], Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Oslo University Hospital [Oslo], Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), University College of London [London] (UCL), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Myocarditis, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV]Life Sciences [q-bio], Pulmonary embolism, ACE2, COVID-19, Heart failure, Thrombosis, Acute coronary syndromes, Arrhythmias, Cardiogenic shock, Biomarkers, Venous thromboembolism
Abstract: International audience; Aims - Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been repeated outbreaks across the globe. The aim of this two-part series is to provide practical knowledge and guidance to aid clinicians in the diagnosis and management of cardiovascular disease (CVD) in association with COVID-19. Methods and results - A narrative literature review of the available evidence has been performed, and the resulting information has been organized into two parts. The first, reported here, focuses on the epidemiology, pathophysiology, and diagnosis of cardiovascular (CV) conditions that may be manifest in patients with COVID-19. The second part, which will follow in a later edition of the journal, addresses the topics of care pathways, treatment, and follow-up of CV conditions in patients with COVID-19. Conclusion - This comprehensive review is not a formal guideline but rather a document that provides a summary of current knowledge and guidance to practicing clinicians managing patients with CVD and COVID-19. The recommendations are mainly the result of observations and personal experience from healthcare providers. Therefore, the information provided here may be subject to change with increasing knowledge, evidence from prospective studies, and changes in the pandemic. Likewise, the guidance provided in the document should not interfere with recommendations provided by local and national healthcare authorities.
Published: 2022

2. Neutrophil to lymphocyte ratio is not related to carotid atherosclerosis progression and cardiovascular events in the primary prevention of cardiovascular disease: Results from the IMPROVE study

Author: Mannarino, M. R., Bianconi, V., Gigante, B., Strawbridge, R. J., Savonen, K., Kurl, S., Giral, P., Smit, A., Eriksson, P., Tremoli, E., Veglia, F., Baldassarre, D., Pirro, M., Groningen Kidney Center (GKC), Translational Immunology Groningen (TRIGR), Università degli Studi di Perugia (UNIPG), Karolinska Institutet [Stockholm], University of Glasgow, University of Kuopio, University of Eastern Finland, Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University Medical Center Groningen [Groningen] (UMCG), Maria Cecilia Hospital [Cotignola], Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), and Università degli Studi di Milano [Milano] (UNIMI)
Subjects: Carotid Artery Diseases, IMT, Neutrophils, cardiovascular, fungi, neutrophil, lymphocyte, prospective, Carotid Intima-Media Thickness, NLR, Primary Prevention, carotid, Cardiovascular Diseases, Risk Factors, cardiovascular system, Humans, cardiovascular diseases, Lymphocytes, Prospective Studies, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Inflammation is a component of the pathogenesis of atherosclerosis and is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). The neutrophil to lymphocyte ratio (NLR) is a possible inflammation metric for the detection of ASCVD risk, although results of prospective studies are highly inconsistent on this topic. We investigated the cross-sectional relationship between NLR and carotid intima-media thickness (cIMT) in subjects at moderate-to-high ASCVD risk. The prospective association between NLR, cIMT progression, and incident vascular events (VEs) was also explored. In 3341 subjects from the IMT-Progression as Predictors of VEs (IMPROVE) study, we analyzed the association between NLR, cIMT, and its 15-month progression. The association between NLR and incident VEs was also investigated. NLR was positively associated with cross-sectional measures of cIMT, but not with cIMT progression. The association between NLR and cross-sectional cIMT measures was abolished when adjusted for confounders. No association was found between NRL and incident VEs. Similarly, there were no significant differences in the hazard ratios (HRs) of VEs across NLR quartiles. NLR was neither associated with the presence and progression of carotid atherosclerosis, nor with the risk of VEs. Our findings do not support the role of NLR as a predictor of the risk of atherosclerosis progression and ASCVD events in subjects at moderate-to-high ASCVD risk, in primary prevention. However, the usefulness of NLR for patients at a different level of ASCVD risk cannot be inferred from this study.
Published: 2022

3. Genetic variation in CADM2 as a link between psychological traits and obesity

Author: Daniel J. Smith, Laura M. Lyall, Keira J.A. Johnston, Angela Silveira, Bruna Gigante, Joey Ward, Amy Ferguson, Hugh Watkins, Bengt Sennblad, Anuj Goel, Philippe Giral, Fabrizio Veglia, Breda Cullen, Damiano Baldassarre, Steve E. Humphries, Julia Morris, Anders Hamsten, Elena Tremoli, Donald M. Lyall, Rona J. Strawbridge, Ulf de Faire, Nicholas Graham, Mark E.S. Bailey, Andries J. Smit, University of Glasgow, Università degli Studi di Milano [Milano] (UNIMI), Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), The Institute of Environmental Medicine [Stockholm] (IMM), Karolinska Institutet [Stockholm], Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Radcliffe Department of Medicine [Oxford], University of Oxford [Oxford], The Wellcome Trust Centre for Human Genetics [Oxford], University College of London [London] (UCL), University of Edinburgh, Stockholm Bioinformatics Center (SBC), Stockholm University, Uppsala University, University Medical Center Groningen [Groningen] (UMCG), University of Groningen [Groningen], and Groningen Kidney Center (GKC)
Subjects: 0301 basic medicine, Male, Bipolar Disorder, [SDV]Life Sciences [q-bio], Obesity/genetics, LOCI, lcsh:Medicine, Genome-wide association study, Bioinformatics, 0302 clinical medicine, Genetics research, lcsh:Science, RISK, Multidisciplinary, Bipolar Disorder/genetics, Endocrine system and metabolic diseases, Middle Aged, Neuroticism, Anxiety Disorders, 3. Good health, INSIGHTS, Cardiovascular diseases, Medical genetics, Major depressive disorder, Female, Cell Adhesion Molecules/genetics, Depressive Disorder, Major/genetics, Medical Genetics, EXPRESSION, medicine.medical_specialty, Quantitative Trait Loci, Quantitative trait locus, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Risk-Taking, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Genetic variation, medicine, Humans, Genetic Predisposition to Disease, Bipolar disorder, Obesity, GENOME-WIDE ASSOCIATION, COMMON, METAANALYSIS, Medicinsk genetik, Aged, [SDV.GEN]Life Sciences [q-bio]/Genetics, Depressive Disorder, Major, ENERGY HOMEOSTASIS, lcsh:R, Genetic Variation, medicine.disease, BODY-MASS INDEX, Affect, 030104 developmental biology, VISUALIZATION, lcsh:Q, Psychiatric disorders, Anxiety Disorders/genetics, Cell Adhesion Molecules, 030217 neurology & neurosurgery
Abstract: CADM2 has been associated with a range of behavioural and metabolic traits, including physical activity, risk-taking, educational attainment, alcohol and cannabis use and obesity. Here, we set out to determine whether CADM2 contributes to mechanisms shared between mental and physical health disorders. We assessed genetic variants in the CADM2 locus for association with phenotypes in the UK Biobank, IMPROVE, PROCARDIS and SCARFSHEEP studies, before performing meta-analyses. A wide range of metabolic phenotypes were meta-analysed. Psychological phenotypes analysed in UK Biobank only were major depressive disorder, generalised anxiety disorder, bipolar disorder, neuroticism, mood instability and risk-taking behaviour. In UK Biobank, four, 88 and 172 genetic variants were significantly (p −5) associated with neuroticism, mood instability and risk-taking respectively. In meta-analyses of 4 cohorts, we identified 362, 63 and 11 genetic variants significantly (p −5) associated with BMI, SBP and CRP respectively. Genetic effects on BMI, CRP and risk-taking were all positively correlated, and were consistently inversely correlated with genetic effects on SBP, mood instability and neuroticism. Conditional analyses suggested an overlap in the signals for physical and psychological traits. Many significant variants had genotype-specific effects on CADM2 expression levels in adult brain and adipose tissues. CADM2 variants influence a wide range of both psychological and metabolic traits, suggesting common biological mechanisms across phenotypes via regulation of CADM2 expression levels in adipose tissue. Functional studies of CADM2 are required to fully understand mechanisms connecting mental and physical health conditions.
Published: 2019

4. Intake of food rich in saturated fat in relation to subclinical atherosclerosis and potential modulating effects from single genetic variants

Author: Laguzzi, Federica, Maitusong, Buamina, Strawbridge, Rona J., Baldassarre, Damiano, Veglia, Fabrizio, Humphries, Steve E., Rauramaa, Rainer, Kurl, Sudhir, Smit, Andries J., Giral, Philippe, Silveira, Angela, Tremoli, Elena, Hamsten, Anders, de Faire, Ulf, Gigante, Bruna, Leander, Karin, Sirtori, C. R., Calabresi, L., Amato, M., Frigerio, B., Ravani, A., Sansaro, D., Tedesco, C., Coggi, D., Capra, N., Bonomi, A., Eriksson, P., Cooper, J., Acharya, J., Savonen, K., Huttunen, K., Rauramaa, E., Penttila, I. M., Törrönen, J., van Gessel, A. I., van Roon, A. M., Nicolai, A., Mulder, D. J., Kontush, A., Carrié, A., Gallo, A., Karppi, J., Nurmi, T., Nyyssönen, K., Tuomainen, T. P., Tuomainen, J., Kauhanen, J., Sennblad, B., Pirro, M., Vaudo, G., Siepi, D., Lupattelli, G., Mannarino, M. R., Bianconi, V., Groningen Kidney Center (GKC), Translational Immunology Groningen (TRIGR), Karolinska Institutet [Stockholm], Xinjiang University, University of Glasgow, Università degli Studi di Milano [Milano] (UNIMI), Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), University College of London [London] (UCL), University of Kuopio, University of Eastern Finland, University Medical Center Groningen [Groningen] (UMCG), Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, medicine.medical_specialty, Multivariate analysis, Cross-sectional study, Science, [SDV]Life Sciences [q-bio], Saturated fat, Cardiology, Disease, 030204 cardiovascular system & hematology, Logistic regression, Carotid Intima-Media Thickness, Article, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Genetics, Medicine, Humans, Genetic Predisposition to Disease, 030212 general & internal medicine, Aged, Multidisciplinary, business.industry, Middle Aged, Atherosclerosis, Dietary Fats, 3. Good health, Endocrinology, Blood pressure, Intima-media thickness, Cohort, cardiovascular system, Dietary Fats/adverse effects, Female, Atherosclerosis/epidemiology, business, Biomarkers
Abstract: The relationship between intake of saturated fats and subclinical atherosclerosis, as well as the possible influence of genetic variants, is poorly understood and investigated. We aimed to investigate this relationship, with a hypothesis that it would be positive, and to explore whether genetics may modulate it, using data from a European cohort including 3,407 participants aged 54–79 at high risk of cardiovascular disease. Subclinical atherosclerosis was assessed by carotid intima-media thickness (C-IMT), measured at baseline and after 30 months. Logistic regression (OR; 95% CI) was employed to assess the association between high intake of food rich in saturated fat (vs. low) and: (1) the mean and the maximum values of C-IMT in the whole carotid artery (C-IMTmean, C-IMTmax), in the bifurcation (Bif-), the common (CC-) and internal (ICA-) carotid arteries at baseline (binary, cut-point ≥ 75th), and (2) C-IMT progression (binary, cut-point > zero). For the genetic-diet interaction analyses, we considered 100,350 genetic variants. We defined interaction as departure from additivity of effects. After age- and sex-adjustment, high intake of saturated fat was associated with increased C-IMTmean (OR:1.27;1.06–1.47), CC-IMTmean (OR:1.22;1.04–1.44) and ICA-IMTmean (OR:1.26;1.07–1.48). However, in multivariate analysis results were no longer significant. No clear associations were observed between high intake of saturated fat and risk of atherosclerotic progression. There was no evidence of interactions between high intake of saturated fat and any of the genetic variants considered, after multiple testing corrections. High intake of saturated fats was not independently associated with subclinical atherosclerosis. Moreover, we did not identify any significant genetic-dietary fat interactions in relation to risk of subclinical atherosclerosis.
Published: 2021

5. Cardiac procedural myocardial injury, infarction, and mortality in patients undergoing elective percutaneous coronary intervention: a pooled analysis of patient-level data

Author: Silvain, Johanne, Zeitouni, Michel, Paradies, Valeria, Zheng, Huili, Ndrepepa, Gjin, Cavallini, Claudio, Feldman, Dimitri, Sharma, Samin, Mehilli, Julinda, Gili, Sebastiano, Barbato, Emanuele, Tarantini, Giuseppe, Ooi, Sze, von Birgelen, Clemens, Jaffe, Allan, Thygesen, Kristian, Montalescot, Gilles, Bulluck, Heerajnarain, Hausenloy, Derek, Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Maasstad Hospital, National University Health System [Singapore] (NUHS), Deutsches Herzzentrum München (DHM), Ospedale 'Santa Maria della Misericordia' = University Hospital 'Santa Maria della Misericordia', Weill Medical College of Cornell University [New York], Icahn School of Medicine at Mount Sinai [New York] (MSSM), Ludwig-Maximilians-Universität München (LMU), Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), University of Naples Federico II, University of Padua, Prince of Wales Hospital, University of Twente [Netherlands], Mayo Clinic [Rochester], Aarhus University Hospital, Norwich University, University College of London [London] (UCL), Duke-National University of Singapore Graduate Medical School, Silvain, Johanne, Zeitouni, Michel, Paradies, Valeria, Zheng, Huili L, Ndrepepa, Gjin, Cavallini, Claudio, Feldman, Dimitri N, Sharma, Samin K, Mehilli, Julinda, Gili, Sebastiano, Barbato, Emanuele, Tarantini, Giuseppe, Ooi, Sze Y, von Birgelen, Clemen, Jaffe, Allan S, Thygesen, Kristian, Montalescot, Gille, Bulluck, Heerajnarain, and Hausenloy, Derek J
Subjects: heart mortality, Procedural complication, Myocardial infarction, Elective PCI, Myocardial injury, Procedural myocardial infarction, Procedural myocardial injury, percutaneous coronary intervention, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, health care economics and organizations
Abstract: International audience; AimsThe prognostic importance of cardiac procedural myocardial injury and myocardial infarction (MI) in chronic coronary syndrome (CCS) patients undergoing elective percutaneous coronary intervention (PCI) is still debated.Methods and resultsWe analysed individual data of 9081 patients undergoing elective PCI with normal pre-PCI baseline cardiac troponin (cTn) levels. Multivariate models evaluated the association between post-PCI elevations in cTn and 1-year mortality, while an interval analysis evaluated the impact of the size of the myocardial injury on mortality. Our analysis was performed in the overall population and also according to the type of cTn used [52.0% had high-sensitivity cTn (hs-cTn)]. Procedural myocardial injury, as defined by the Fourth Universal Definition of MI (UDMI) [post-PCI cTn elevation ≥1 × 99th percentile upper reference limit (URL)], occurred in 52.8% of patients and was not associated with 1-year mortality [adj odds ratio (OR), 1.35, 95% confidence interval (CI) (0.84–1.77), P = 0.21]. The association between post-PCI cTn elevation and 1-year mortality was significant starting ≥3 × 99th percentile URL. Major myocardial injury defined by post-PCI ≥5 × 99th percentile URL occurred in 18.2% of patients and was associated with a two-fold increase in the adjusted odds of 1-year mortality [2.29, 95% CI (1.32–3.97), P = 0.004]. In the subset of patients for whom periprocedural evidence of ischaemia was collected (n = 2316), Type 4a MI defined by the Fourth UDMI occurred in 12.7% of patients and was strongly associated with 1-year mortality [adj OR 3.21, 95% CI (1.42–7.27), P = 0.005]. We also present our results according to the type of troponin used (hs-cTn or conventional troponin).ConclusionOur analysis has demonstrated that in CCS patients with normal baseline cTn levels, the post-PCI cTn elevation of ≥5 × 99th percentile URL used to define Type 4a MI is associated with 1-year mortality and could be used to detect ‘major’ procedural myocardial injury in the absence of procedural complications or evidence of new myocardial ischaemia.
Published: 2021

6. The Association between HDL-C and Subclinical Atherosclerosis Depends on CETP Plasma Concentration: Insights from the IMPROVE Study

Author: Colombo, Gualtiero, Bianconi, Vanessa, Bonomi, Alice, Simonelli, Sara, Amato, Mauro, Frigerio, Beatrice, Ravani, Alessio, Vitali, Cecilia, Sansaro, Daniela, Coggi, Daniela, Mannarino, Massimo, Savonen, Kai, Kurl, Sudhir, Gigante, Bruna, Smit, Andries, Giral, Philippe, Tremoli, Elena, Calabresi, Laura, Veglia, Fabrizio, Pirro, Matteo, Baldassarre, Damiano, Group, on behalf of the IMPROVE Study, Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Università degli Studi di Perugia (UNIPG), Università degli Studi di Milano [Milano] (UNIMI), Perelman School of Medicine, University of Pennsylvania [Philadelphia], University of Eastern Finland, Karolinska Institutet [Stockholm], University Medical Center Groningen [Groningen] (UMCG), Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), and Groningen Kidney Center (GKC)
Subjects: Carotid intima‐media thickness, carotid intima-media thickness, [SDV]Life Sciences [q-bio], cholesteryl ester transfer protein, Single‐nucleotide polymorphisms, Article, carbohydrates (lipids), HDL‐C, lcsh:Biology (General), single-nucleotide polymorphisms, cardiovascular system, lipids (amino acids, peptides, and proteins), HDL-C, cardiovascular diseases, atherosclerosis, lcsh:QH301-705.5
Abstract: The impact of cholesteryl ester transfer protein (CETP) on atherosclerosis is highly debated. This study aimed to investigate the associations between plasma CETP or CETP genotypes and carotid intima-media thickness (cIMT) and the influence of high-density lipoprotein cholesterol (HDL-C) on these associations. Plasma CETP and HDL-C concentrations were measured in 552 subjects free of any pharmacological treatment from the IMPROVE cohort, which includes 3711 European subjects at high cardiovascular risk. CETP single-nucleotide polymorphisms (SNPs) and cIMT measures (cIMTmax, cIMTmean–max of bifurcations, common and internal carotids, plaque-free common carotid [PF CC]-IMTmean) were available for the full cohort. In drug-free subjects, plasma CETP correlated with HDL-C levels (r = 0.19, p &lt, 0.0001), but not with cIMT variables. When stratified according to HDL-C quartiles, CETP positively correlated with cIMTmax and cIMTmean–max, but not with PF CC-IMTmean, in the top HDL-C quartile only. Positive associations between the CETP concentration and cIMTmax or cIMTmean–max were found in the top HDL-C quartile, whereas HDL-C levels were negatively correlated with cIMTmax and cIMTmean–max when the CETP concentration was below the median (HDL-C × CETP interaction, p = 0.001 and p = 0.003 for cIMTmax and cIMTmean–max, respectively). In the full cohort, three CETP SNPs (rs34760410, rs12920974, rs12708968) were positively associated with cIMTmax. rs12444708 exhibited a significant interaction with HDL-C levels in the prediction of cIMTmax. In conclusion, a significant interplay was found between plasma CETP and/or CETP genotype and HDL-C in the prediction of carotid plaque thickness, as indexed by cIMTmax. This suggests that the association of HDL-C with carotid atherosclerosis is CETP-dependent.
Published: 2021

7. SCN5A Mutation Type and a Genetic Risk Score Associate Variably with Brugada Syndrome Phenotype in SCN5A Families

Author: Peter Lichtner, Thomas Meitinger, Wataru Shimizu, Alison Muir, F. Kyndt, Michael W.T. Tanck, Seiko Ohno, Martina Muggenthaler, Michael J. Ackerman, Vincent Probst, Stephen P. Page, Jean-Jacques Schott, Silvia Castelletti, Hariharan Raju, Jean-Baptiste Gourraud, Joseph Galvin, Taisuke Ishikawa, Eline A. Nannenberg, Dan M. Roden, Doris Škorić-Milosavljević, Kazuhiro Takahashi, Pascal P. McKeown, Federica Dagradi, Lia Crotti, Yanushi D. Wijeyeratne, Julien Barc, Yuka Mizusawa, Peter J. Schwartz, Michael Papadakis, Margherita Torchio, Sanjay Sharma, Velislav N. Batchvarov, Naomasa Makita, Richard Redon, Christian Veltmann, Elijah R. Behr, Takeshi Aiba, Martin Borggrefe, Rafik Tadros, Connie R. Bezzina, J. Martijn Bos, David J. Tester, Isabelle Denjoy, Minoru Horie, Arthur A.M. Wilde, St George's, University of London, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centro Cardiologico Monzino [Milano], Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS)-Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI), Mayo Clinic [Rochester], Belfast Health and Social Care Trust, Hannover Medical School [Hannover] (MHH), University of Shiga Prefecture, National Cerebral and Cardiovascular Center (NCCC - OSAKA), Osaka University [Osaka], Leeds Teaching Hospitals NHS Trust, University of Dublin, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Helmholtz-Zentrum München (HZM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Iwate Prefectural University [Takizawa], Vanderbilt University School of Medicine [Nashville], University of Heidelberg, Medical Faculty, Wijeyeratne, Y, Tanck, M, Mizusawa, Y, Batchvarov, V, Barc, J, Crotti, L, Bos, J, Tester, D, Muir, A, Veltmann, C, Ohno, S, Page, S, Galvin, J, Tadros, R, Muggenthaler, M, Raju, H, Denjoy, I, Schott, J, Gourraud, J, Skoric-Milosavljevic, D, Nannenberg, E, Redon, R, Papadakis, M, Kyndt, F, Dagradi, F, Castelletti, S, Torchio, M, Meitinger, T, Lichtner, P, Ishikawa, T, Wilde, A, Takahashi, K, Sharma, S, Roden, D, Borggrefe, M, Mckeown, P, Shimizu, W, Horie, M, Makita, N, Aiba, T, Ackerman, M, Schwartz, P, Probst, V, Bezzina, C, Behr, E, Unité de recherche de l'institut du thorax (ITX-lab), Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano = University of Milan (UNIMI)-Università degli Studi di Milano = University of Milan (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Helmholtz Zentrum München = German Research Center for Environmental Health, HAL-SU, Gestionnaire, Epidemiology and Data Science, APH - Methodology, Graduate School, ACS - Heart failure & arrhythmias, Amsterdam Reproduction & Development (AR&D), Human Genetics, Cardiology, ACS - Pulmonary hypertension & thrombosis, and ACS - Atherosclerosis & ischemic syndromes
Subjects: genetics, human, congenital, hereditary, and neonatal diseases and abnormalities, Scn5a gene, phenotype, BIO/18 - GENETICA, 030204 cardiovascular system & hematology, risk score, 03 medical and health sciences, 0302 clinical medicine, Brugada Syndrome, Genetics, Human, Penetrance, Phenotype, Risk Score, Medicine, genetics, Brugada syndrome, 030212 general & internal medicine, human, cardiovascular diseases, Genetic risk, penetrance, Genetics, Framingham Risk Score, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, fungi, General Medicine, Original Articles, MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, medicine.disease, Human genetics, 3. Good health, Brugada ECG Pattern, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, cardiovascular system, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Supplemental Digital Content is available in the text., Background: Brugada syndrome (BrS) is characterized by the type 1 Brugada ECG pattern. Pathogenic rare variants in SCN5A (mutations) are identified in 20% of BrS families in whom incomplete penetrance and genotype-negative phenotype-positive individuals are observed. E1784K-SCN5A is the most common SCN5A mutation identified. We determined the association of a BrS genetic risk score (BrS-GRS) and SCN5A mutation type on BrS phenotype in BrS families with SCN5A mutations. Methods: Subjects with a spontaneous type 1 pattern or positive/negative drug challenge from cohorts harboring SCN5A mutations were recruited from 16 centers (n=312). Single nucleotide polymorphisms previously associated with BrS at genome-wide significance were studied in both cohorts: rs11708996, rs10428132, and rs9388451. An additive linear genetic model for the BrS-GRS was assumed (6 single nucleotide polymorphism risk alleles). Results: In the total population (n=312), BrS-GRS ≥4 risk alleles yielded an odds ratio of 4.15 for BrS phenotype ([95% CI, 1.45–11.85]; P=0.0078). Among SCN5A-positive individuals (n=258), BrS-GRS ≥4 risk alleles yielded an odds ratio of 2.35 ([95% CI, 0.89–6.22]; P=0.0846). In SCN5A-negative relatives (n=54), BrS-GRS ≥4 alleles yielded an odds ratio of 22.29 ([95% CI, 1.84–269.30]; P=0.0146). Among E1784K-SCN5A positive family members (n=79), hosting ≥4 risk alleles gave an odds ratio=5.12 ([95% CI, 1.93–13.62]; P=0.0011). Conclusions: Common genetic variation is associated with variable expressivity of BrS phenotype in SCN5A families, explaining in part incomplete penetrance and genotype-negative phenotype-positive individuals. SCN5A mutation genotype and a BrS-GRS associate with BrS phenotype, but the strength of association varies according to presence of a SCN5A mutation and severity of loss of function.
Published: 2020

8. The impact of chronic kidney disease in women undergoing transcatheter aortic valve replacement: Analysis from the Women's INternational Transcatheter Aortic Valve Implantation (WIN‐TAVI) registry

Author: Nicholas Dumonteil, Piera Capranzaro, Samantha Sartori, Bimmer E. Claessen, Roxana Mehran, Daniela Trabattoni, Davide Cao, Thierry Lefèvre, Didier Tchetche, Usman Baber, Alaide Chieffo, Anna Sonia Petronio, Rishi Chandiramani, Dhrubajyoti Bandyopadhyay, Chiara Fraccaro, Annapoorna Kini, Christoph Naber, Patrizia Presbitero, Nicolas M. Van Mieghem, Jaya Chandrasekhar, Marie Claude Morice, Ghada W. Mikhail, Gennaro Sardella, Julinda Mehilli, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Clinique Pasteur [Toulouse], Ludwig-Maximilians-Universität München (LMU), Hôpital Privé Jacques Cartier [Massy], Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), University of Catania [Italy], Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hôpital de Rangueil, CHU Toulouse [Toulouse], Universita degli Studi di Padova, Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Imperial College London, San Raffaele Scientific Institute, Vita-Salute San Raffaele University and Center for Translational Genomics and Bioinformatics, and Cardiology
Subjects: medicine.medical_treatment, [SDV]Life Sciences [q-bio], aortic valve stenosis, 030204 cardiovascular system & hematology, urologic and male genital diseases, time factors, renal insufficiency, 0302 clinical medicine, Valve replacement, 80 and over, risk factors, 030212 general & internal medicine, Myocardial infarction, humans, Aged, 80 and over, glomerular filtration rate, Hazard ratio, risk assessment, General Medicine, aortic valve, female genital diseases and pregnancy complications, 3. Good health, chronic, aged, retrospective studies, female, Cardiology, transcatheter aortic valve replacement, Hemodialysis, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, kidney, Renal function, aortic stenosis, chronic kidney disease, WIN-TAVI registry, aged, 80 and over, registries, severity of illness index, sex factors, treatment outcome, renal insufficiency, chronic, 03 medical and health sciences, Internal medicine, medicine, Radiology, Nuclear Medicine and imaging, Renal Insufficiency, Chronic, business.industry, Percutaneous coronary intervention, EuroSCORE, medicine.disease, business, Kidney disease
Abstract: International audience; Background: The prevalence of both chronic kidney disease (CKD) and aortic stenosis (AS) increase with age. Although baseline CKD is frequent in patients undergoing transcatheter aortic valve replacement (TAVR), its significance among women is largely unknown.Methods: Women's INternational Transcatheter Aortic Valve Implantation (WIN-TAVI) is a multinational, prospective registry of women undergoing TAVR for severe AS. We included patients with available baseline estimated glomerular filtration rate (eGFR) and completed 1-year follow-up. Patients were categorized into three groups based on their eGFR: No CKD (normal kidney function to stage 2 CKD: eGFR ≥60 ml/min/1.73 m2 ); (b) mild CKD (stage 3a CKD: eGFR = 45-59 ml/min/1.73 m2 ); and (c) moderate/severe CKD (stage ≥3b CKD: eGFR
Published: 2020

9. Alcohol consumption in relation to carotid subclinical atherosclerosis and its progression: results from a European longitudinal multicentre study

Author: Laguzzi, F., Baldassarre, D., Veglia, F., Strawbridge, R. J., Humphries, S. E., Rauramaa, R., Smit, A. J., Giral, P., Silveira, A., Tremoli, E., Hamsten, A., de Faire, U., Frumento, P., Leander, K., Sirtori, C. R., Castelnuovo, S., Amato, M., Frigerio, B., Ravani, A., Sansaro, D., Tedesco, C., Coggi, D., Bonomi, A., Eriksson, M. J., Cooper, J., Acharya, J., Huttunen, K., Rauramaa, E., Pekkarinen, H., Penttila, I. M., Torronen, J., van Gessel, A. I., van Roon, A. M., Teune, G. C., Kuipers, W. D., Bruin, M., Nicolai, A., Haarsma-Jorritsma, P., Mulder, D. J., Bilo, H. J. G., Smeets, G. H., Beaudeux, J. L., Kahn, J. F., Carreau, V., Kontush, A., Karppi, J., Nurmi, T., Nyyssonen, K., Salonen, R., Tuomainen, T. P., Tuomainen, J., Kauhanen, J., Vaudo, G., Alaeddin, A., Siepi, D., Lupattelli, G., Mannarino, E., Groningen Kidney Center (GKC), The Institute of Environmental Medicine [Stockholm] (IMM), Karolinska Institutet [Stockholm], Università degli Studi di Milano [Milano] (UNIMI), Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), University of Glasgow, Institute of Cardiovascular and Medical Sciences [Glasgow], University College of London [London] (UCL), University of Kuopio, University Medical Center Groningen [Groningen] (UMCG), University of Groningen [Groningen], Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Karolinska University Hospital [Stockholm]
Subjects: Male, medicine.medical_specialty, Epidemiology, [SDV]Life Sciences [q-bio], Physical activity, Medicine (miscellaneous), Alcohol drinking, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, medicine.artery, Internal medicine, medicine, Humans, 030212 general & internal medicine, Carotid intima-media thickness, Finland, Netherlands, Sweden, Nutrition and Dietetics, Progression, business.industry, Confounding, European population, Original Contribution, Atherosclerosis, 3. Good health, Italy, Subclinical atherosclerosis, Cardiology, Female, France, Internal carotid artery, business, Alcohol consumption, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background/Aim The association between alcohol consumption and subclinical atherosclerosis is still unclear. Using data from a European multicentre study, we assess subclinical atherosclerosis and its 30-month progression by carotid intima-media thickness (C-IMT) measurements, and correlate this information with self-reported data on alcohol consumption. Methods Between 2002–2004, 1772 men and 1931 women aged 54–79 years with at least three risk factors for cardiovascular disease (CVD) were recruited in Italy, France, Netherlands, Sweden, and Finland. Self-reported alcohol consumption, assessed at baseline, was categorized as follows: none (0 g/d), very-low (0 − 5 g/d), low (> 5 to ≤ 10 g/d), moderate (> 10 to ≤ 20 g/d for women, > 10 to ≤ 30 g/d for men) and high (> 20 g/d for women, > 30 g/d for men). C-IMT was measured in millimeters at baseline and after 30 months. Measurements consisted of the mean and maximum values of the common carotids (CC), internal carotid artery (ICA), and bifurcations (Bif) and whole carotid tree. We used quantile regression to describe the associations between C-IMT measures and alcohol consumption categories, adjusting for sex, age, physical activity, education, smoking, diet, and latitude. Results Adjusted differences between median C-IMT values in different levels of alcohol consumption (vs. very-low) showed that moderate alcohol consumption was associated with lower C-IMTmax[− 0.17(95%CI − 0.32; − 0.02)], and Bif-IMTmean[− 0.07(95%CI − 0.13; − 0.01)] at baseline and decreasing C-IMTmean[− 0.006 (95%CI − 0.011; − 0.000)], Bif-IMTmean[− 0.016(95%CI − 0.027; − 0.005)], ICA-IMTmean[− 0.009(95% − 0.016; − 0.002)] and ICA-IMTmax[− 0.016(95%: − 0.032; − 0.000)] after 30 months. There was no evidence of departure from linearity in the association between alcohol consumption and C-IMT. Conclusion In this European population at high risk of CVD, findings show an inverse relation between moderate alcohol consumption and carotid subclinical atherosclerosis and its 30-month progression, independently of several potential confounders.
Published: 2020

10. Sex-specific predictors of PCSK9 levels in a European population: The IMPROVE Study

Author: Ferri, Nicola, Ruscica, Massimiliano, Coggi, Daniela, Bonomi, Alice, Amato, Mauro, Frigerio, Beatrice, Sansaro, Daniela, Ravani, Alessio, Veglia, Fabrizio, Capra, Nicolò, Lupo, Maria, Macchi, Chiara, Castelnuovo, Samuela, Savonen, Kai, Silveira, Angela, Kurl, Sudhir, Giral, Philippe, Pirro, Matteo, Strawbridge, Rona, Gigante, Bruna, Smit, Andries, Tremoli, Elena, Colombo, Gualtiero, Baldassarre, Damiano, Groningen Kidney Center (GKC), Translational Immunology Groningen (TRIGR), Universita degli Studi di Padova, Università degli Studi di Milano [Milano] (UNIMI), Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Karolinska Institutet [Stockholm], University of Eastern Finland, Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli Studi di Perugia (UNIPG), University of Glasgow, and University Medical Center Groningen [Groningen] (UMCG)
Subjects: Male, Sweden, RISK, [SDV]Life Sciences [q-bio], SUBTILISIN/KEXIN TYPE 9, DETERMINANTS, ASSOCIATION, Atherosclerosis, PCSK9 predictors, INTIMA-MEDIA THICKNESS, MECHANISMS, Europe, Italy, CIRCULATING PCSK9, CARDIOVASCULAR-DISEASE, Sex differences, Humans, Female, France, Proprotein Convertase 9, PLASMA PCSK9, Biomarkers, Finland, Cardiovascular risk factors, Netherlands
Abstract: International audience; Background and aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the key regulators of low-density lipoprotein cholesterol plasma levels. Circulating PCSK9, which differs between genders, represents a valid pharmacological target for preventing cardiovascular (CV) events. We aimed to investigate sex-related associations between PCSK9 plasma levels and biochemical and anthropomorphic factors, and familial and personal morbidities, in a large European cohort (n = 3673) of men (47.9%) and women (52.1%).Methods: Individuals (aged 54-79 years) free of CV diseases were enrolled in seven centers of five European countries: Finland, France, Italy, the Netherlands, and Sweden. PCSK9 plasma levels were measured by ELISA.Results: PCSK9 was higher in women than in men. Multiple linear regression analysis showed that latitude, sex, and treatments with statins and fibrates were the strongest predictors of PCSK9 in the whole group. These variables, together with triglycerides and high-density lipoprotein cholesterol, were also associated with PCSK9 in men or women. Mean corpuscular hemoglobin concentration and pack-years were PCSK9 independent predictors in women, whereas hypercholesterolemia and physical activity were independent predictors in men. The associations between PCSK9 and latitude, uric acid, diabetes, hypercholesterolemia and physical activity were significantly different in men and women (pinteraction
Published: 2020

11. Genetic Variants Associated with Non-Alcoholic Fatty Liver Disease Do Not Associate with Measures of Sub-Clinical Atherosclerosis: Results from the IMPROVE Study

Author: Castaldo, Luigi, Laguzzi, Federica, Strawbridge, Rona J., Baldassarre, Damiano, Veglia, Fabrizio, Vigo, Lorenzo, Tremoli, Elena, de Faire, Ulf, Eriksson, Per, Smit, Andries J., Aubrecht, Jiri, Leander, Karin, Pirro, Matteo, Giral, Philippe, Ritieni, Alberto, Di Minno, Giovanni, Mälarstig, Anders, Gigante, Bruna, 'Federico II' University of Naples Medical School, Karolinska Institutet [Stockholm], University of Glasgow, Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), University of Milan, University Medical Center Groningen [Groningen] (UMCG), Takeda Pharmaceuticals International GmbH, Perugia General Hospital, Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Groningen Kidney Center (GKC), Castaldo, L., Laguzzi, F., Strawbridge, R. J., Baldassarre, D., Veglia, F., Vigo, L., Tremoli, E., de Faire, U., Eriksson, P., Smit, A. J., Aubrecht, J., Leander, K., Pirro, M., Giral, P., Ritieni, A., Di Minno, G., Malarstig, A., and Gigante, B.
Subjects: Male, lcsh:QH426-470, carotid intima-media thickness, Polymorphism, Single Nucleotide, INTIMA-MEDIA THICKNESS, Article, TM6SF2, Carotid intima-media thickne, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Humans, cardiovascular diseases, CONFERS SUSCEPTIBILITY, Genetic Association Studies, POPULATION, Aged, RISK, CHOLESTEROL, non-alcoholic fatty liver disease, Alanine Transaminase, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Atherosclerosis, lcsh:Genetics, Carotid Arteries, Amino Acid Substitution, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, CARDIOVASCULAR-DISEASE, cardiovascular system, CORONARY-ARTERY-DISEASE, HEART, Female, alanine aminotransferase and genetic association study, GCKR
Abstract: Non-alcoholic fatty liver disease (NAFLD) and atherosclerosis-related cardiovascular diseases (CVD) share common metabolic pathways. We explored the association between three NAFLD-associated single nucleotide polymorphisms (SNPs) rs738409, rs10401969, and rs1260326 with sub-clinical atherosclerosis estimated by the carotid intima-media thickness (c-IMT) and the inter-adventitia common carotid artery diameter (ICCAD) in patients free from clinically overt NAFLD and CVD. The study population is the IMPROVE, a multicenter European study (n = 3711). C-IMT measures and ICCAD were recorded using a standardized protocol. Linear regression with an additive genetic model was used to test for association of the three SNPs with c-IMT and ICCAD. In secondary analyses, the association of the three SNPs with c-IMT and ICCAD was tested after stratification by alanine aminotransferase levels (ALT). No associations were found between rs738409, rs1260326, rs10401969, and c-IMT or ICCAD. Rs738409-G and rs10401969-C were associated with ALT levels (p &lt, 0.001). In patients with ALT levels above 28 U/L (highest quartile), we observed an association between rs10401969-C and c-IMT measures of c-IMTmax and c-IMTmean-max (p = 0.018 and 0.021, respectively). In conclusion, NAFLD-associated SNPs do not associate with sub-clinical atherosclerosis measures. However, our results suggest a possible mediating function of impaired liver function on atherosclerosis development.
Published: 2020

12. Towards Precision Medicine With Human iPSCs for Cardiac Channelopathies

Author: Peter J. Schwartz, Joseph C. Wu, Yoshinori Yoshida, Bjorn C. Knollmann, Priyanka Garg, Shinya Yamanaka, Lior Gepstein, Jean-Sébastien Hulot, CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Center for iPS Cell Research and Application (CiRA), Kyoto University [Kyoto], Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), and Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS)
Subjects: Lineage (genetic), Physiology, [SDV]Life Sciences [q-bio], Induced Pluripotent Stem Cells, Computational biology, Disease, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Genome editing, Medicine, CRISPR, Humans, Clustered Regularly Interspaced Short Palindromic Repeats, Precision Medicine, Induced pluripotent stem cell, 030304 developmental biology, Genetic testing, 0303 health sciences, medicine.diagnostic_test, business.industry, Precision medicine, 3. Good health, Long QT Syndrome, DECIPHER, Channelopathies, Cardiology and Cardiovascular Medicine, business
Abstract: International audience; Long-QT syndrome, a frequently fatal inherited arrhythmia syndrome caused by genetic variants (congenital) or drugs (acquired), affects 1 in 2000 people worldwide. Its sentinel event is often sudden cardiac death, which makes preclinical diagnosis by genetic testing potentially life-saving. Unfortunately, clinical experience with genetic testing has shown that it is difficult to correctly identify genetic variants as disease causing. These current deficiencies in accurately assigning pathogenicity led to the discovery of increasing numbers of rare variants classified as variant of uncertain significance. To overcome these challenges, new technologies such as clustered regularly interspaced short palindromic repeats (CRISPR) genome editing can be combined with human induced pluripotent stem cell-derived cardiomyocytes to provide a new approach to decipher pathogenicity of variants of uncertain significance and to better predict arrhythmia risk. To that end, the overarching goal of our network is to establish the utility of induced pluripotent stem cell-based platforms to solve major clinical problems associated with long-QT syndrome by determining how to (1) differentiate pathogenic mutations from background genetic noise, (2) assess existing and novel variants associated with congenital and acquired long-QT syndrome, and (3) provide genotype-and phenotype-guided risk stratification and pharmacological management of long-QT syndrome. To achieve these goals and to further advance the use of induced pluripotent stem cells in disease modeling and drug discovery, our team of investigators for this Leducq Foundation Transatlantic Networks of Excellence proposal will work together to (1) improve differentiation efficiency, cellular maturation, and lineage specificity, (2) develop new assays for high throughput cellular phenotyping, and (3) train young investigators to clinically implement patient-specific genetic modeling.
Published: 2019

13. Safety and efficacy of polymer‐free biolimus‐eluting stents versus ultrathin stents in unprotected left main or coronary bifurcation: A propensity score analysis from the RAIN and CHANCE registries

Author: Zenon Huczek, Roberto Latini, Francesco Romeo, Maurizio Di Biasi, Fabrizio D'Ascenzo, Alfonso Ielasi, Gaetano M. De Ferrari, Luca Gaido, Davide Capodanno, Javier Escaned, Imad Sheiban, Maurizio D'Urbano, Andrea Rognoni, Arnaldo Poli, Alaide Chieffo, Bernardo Cortese, Daniela Trabattoni, Fabrizio Ugo, Massimo Giammaria, Ferdinando Varbella, Satoru Mitomo, Fabio Piazza, Gérard Helft, Grzegorz Smolka, Andrea Gangor, Carlo Di Mario, Andrea Saglietto, Alessandro Bernardi, Leonardo De Luca, Vincenzo Infantino, Alfonso Franzé, University of Turin, Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), University of Milan, Sorbonne Université (SU), University of Silesia in Katowice, Medical University of Warsaw - Poland, IRCCS San Raffaele Scientific Institute [Milan, Italie], and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC)
Subjects: Male, Time Factors, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Coronary artery disease, chemistry.chemical_compound, 0302 clinical medicine, Clinical Protocols, Risk Factors, Registries, 030212 general & internal medicine, Myocardial infarction, Aged, 80 and over, stent thrombosis, Drug-Eluting Stents, General Medicine, Middle Aged, 3. Good health, Drug-eluting stent, Cardiology, Female, Cardiology and Cardiovascular Medicine, drug eluting stent, coronary artery disease, stent restenosis, medicine.medical_specialty, Prosthesis Design, Risk Assessment, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Umirolimus, medicine, Humans, Radiology, Nuclear Medicine and imaging, Propensity Score, Aged, Retrospective Studies, Sirolimus, business.industry, percutaneous coronary intervention, percutaneous coronary intervention complex, Percutaneous coronary intervention, Cardiovascular Agents, medicine.disease, chemistry, Cardiovascular agent, Propensity score matching, business, Mace
Abstract: International audience; OBJECTIVES:Evaluate safety and efficacy of polymer-free biolimus-eluting stents (PF-BESs) versus ultrathin stents in unprotected left main (ULM) or bifurcation.BACKGROUND:PF-BESs due to reduced length of dual antiplatelet therapy (DAPT) are increasingly used. However, there are limited data about safety and efficacy for ULM or bifurcation.METHODS:We selected all-patients treated for ULM or bifurcation from two multicenter real life registries (RAIN [NCT03544294] evaluating ultrathin stents, CHANCE [NCT03622203] appraising PF-BES). After propensity score with matching, the primary endpoint was major adverse cardiac events (MACE; a composite of all-cause death, myocardial infarction, target lesion revascularization [TLR], and stent thrombosis [ST]), while its components along with target vessel revascularization (TVR) secondary endpoints.RESULTS:Three thousand and three patients treated with ultrathin stents and 446 with PF-BESs, resulting respectively in 562 and 281 after propensity score with matching (33 and 22%, respectively, with ULM disease). After 12 (8-20) months, rates of MACE were similar (9 vs. 8%, p = 0.56) without difference in TLR and ST (3.0 vs. 1.7%, p = .19 and 1.8 vs. 1.1%, p = .42). These results were consistent for ULM group (3 vs. 1.7% and 1.8 vs. 1.1%, p = .49 and .76), for non-ULM group (2.1 vs. 3.4%, p = .56 and 1.2 vs. 1.7%, p = .78) and for two-stent strategy (8.7 vs. 4.5% and 4.3 vs. 3.2%, p = .75 and .91). Among patients treated with 1 month of DAPT in both groups, those with ultrathin stents experienced higher rates of MACE related to all-cause death (22 vs. 12%, p = .04) with higher although not significant rates of ST (3 vs. 0%, p = .45).CONCLUSIONS:PF-BES implanted on ULM or BiF offered freedom from TLR and ST comparable to ultrathin stents. PF-BESs patients assuming DAPT for 1 month experienced a lower despite not significant incidence of ST.
Published: 2019

14. Long-Term Follow-Up of Idiopathic Ventricular Fibrillation in a Pediatric Population: Clinical Characteristics, Management, and Complications

Author: Konstantinos Vlachos, Riccardo Cappato, Isabelle Deisenhofer, Yoshifusa Aizawa, Graham Stuart, Thomas Pambrun, Juan Pablo Kaski, Antonio Frontera, Ivan Blankoff, Pierre Bordachar, Linda Koutbi, Takeshi Kitamura, Daniel Scherr, Nicolas Derval, Patrice Scanu, Gerard J. Fahy, Philippe Ritter, Pascal Defaye, Frederic Sacher, Michel Haïssaguerre, Arnaud Denis, Philippe Maury, Martin Manninger, Alice Maltret, Mélèze Hocini, Christelle Marquié, Jean-Luc Pasquié, Saagar Mahida, Pierre Jaïs, Joris Ector, Xavier Pillois, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Chest Hospital, Hôpital Charles Perrens, Cork University Hospital, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Bristol Heart Institute, Cardiac Stimulation and Rhythmology, CHU Grenoble, Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), UCL Institute of Cardiovascular Science London, Department of Cardiology [K.U.Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-University Hospital Gasthuisberg, Service de cardiologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de cardiologie et de pathologie vasculaire [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Herzzentrum München, Centre Hospitalier, Division of Cardiology, Niigata University Graduate School of Medical and Dental Science Niigata Japan., Département de cardiologie, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Toulouse [Toulouse], CHU Necker - Enfants Malades [AP-HP], MORNET, Dominique, Centre hospitalier Charles Perrens [Bordeaux], Università degli Studi di Milano = University of Milan (UNIMI)-Università degli Studi di Milano = University of Milan (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-University Hospital Gasthuisberg [Leuven], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Male, Pediatrics, Cardiac & Cardiovascular Systems, Heart disease, [SDV]Life Sciences [q-bio], Arrhythmias, 030204 cardiovascular system & hematology, Ventricular tachycardia, GUIDELINES, Sudden Cardiac Death, NAV1.5 Voltage-Gated Sodium Channel, Electrocardiography, 0302 clinical medicine, Recurrence, Interquartile range, Arrhythmia and Electrophysiology, Longitudinal Studies, Child, 10. No inequality, Original Research, Hypertrophic cardiomyopathy, Defibrillators, Implantable, 3. Good health, [SDV] Life Sciences [q-bio], Electrophysiology, Natural history, Long QT Syndrome, Phenotype, syncope, Cohort, idiopathic, Female, ventricular tachycardia, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, STANDARDS, medicine.medical_specialty, Adolescent, complications, Long QT syndrome, 03 medical and health sciences, defibrillator, Cardiomyopathy, Hypertrophic, Familial, medicine, Humans, Science & Technology, Myosin Heavy Chains, business.industry, ECG, Ryanodine Receptor Calcium Release Channel, 030208 emergency & critical care medicine, medicine.disease, ventricular fibrillation, Ventricular fibrillation, Tachycardia, Ventricular, Cardiovascular System & Cardiology, business, Cardiac Myosins
Abstract: Background The natural history and long‐term outcome in pediatric patients with idiopathic ventricular fibrillation ( IVF ) are poorly characterized. We sought to define the clinical characteristics and long‐term outcomes of a pediatric cohort with an initial diagnosis of IVF . Methods and Results Patients were included from an International Registry of IVF (consisting of 496 patients). Inclusion criteria were: (1) VF with no identifiable cause following comprehensive analysis for ischemic, electrical or structural heart disease and (2) age ≤16 years. These included 54 pediatric IVF cases (age 12.7±3.7 years, 59% male) among whom 28 (52%) had a previous history of syncope (median 2 syncopal episodes [interquartile range 1]). Thirty‐six (67%) had VF in situations associated with high adrenergic tone. During a median 109±12 months of follow‐up, 31 patients (57%) had recurrence of ventricular arrhythmias, mainly VF . Two patients developed phenotypic expression of an inherited arrhythmia syndrome during follow‐up (hypertrophic cardiomyopathy and long QT syndrome, respectively). A total of 15 patients had positive genetic testing for inherited arrhythmia syndromes. Ten patients (18%) experienced device‐related complications. Three patients (6%) died, 2 due to VF storm. Conclusions In pediatric patients with IVF , a minority develop a definite clinical phenotype during long‐term follow‐up. Recurrent VF is common in this patient group.
Published: 2019

15. Segmentation of the left ventricular endocardium from magnetic resonance images by using different statistical shape models

Author: Enrico G. Caiani, Mark Potse, Roberto M. Lang, Lynn Weinert, Mauro Pepi, Angelo Auricchio, M. Chiara Carminati, Rolf Krause, Gloria Tamborini, Concetta Piazzese, Andrea Colombo, Politecnico di Milano [Milan] (POLIMI), Center for Computational Medicine in Cardiology [Lugano], Università della Svizzera italiana = University of Italian Switzerland (USI), Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Modélisation et calculs pour l'électrophysiologie cardiaque (CARMEN), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), University of Chicago, University of Zurich, Piazzese, Concetta, Università degli Studi di Milano = University of Milan (UNIMI)-Università degli Studi di Milano = University of Milan (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-IHU-LIRYC, and Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux]
Subjects: Male, Models, Anatomic, Computer science, Echocardiography, Three-Dimensional, 030218 nuclear medicine & medical imaging, Ventricular Dysfunction, Left, 0302 clinical medicine, Active shape model, Cardiac MRI, Image segmentation, Left ventricular volume, Statistical shape model, Cardiology and Cardiovascular Medicine, Segmentation, medicine.diagnostic_test, Cardiac cycle, Models, Cardiovascular, Middle Aged, medicine.anatomical_structure, Echocardiography, Principal component analysis, cardiovascular system, Cardiology, Female, medicine.medical_specialty, Magnetic Resonance Imaging, Cine, 610 Medicine & health, Sensitivity and Specificity, 11171 Cardiocentro Ticino, 2705 Cardiology and Cardiovascular Medicine, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, Computer Simulation, Endocardium, Models, Statistical, business.industry, Reproducibility of Results, Magnetic resonance imaging, Pattern recognition, Ventricle, Subtraction Technique, Artificial intelligence, business, 030217 neurology & neurosurgery
Abstract: International audience; We evaluate in this paper different strategies for the construction of a statistical shape model (SSM) of the left ventricle (LV) to be used for segmentation in cardiac magnetic resonance (CMR) images. From a large database of LV surfaces obtained throughout the cardiac cycle from 3D echocardiographic (3DE) LV images, different LV shape models were built by varying the considered phase in the cardiac cycle and the registration procedure employed for surface alignment. Principal component analysis was computed to describe the statistical variability of the SSMs, which were then deformed by applying an active shape model (ASM) approach to segment the LV endocardium in CMR images of 45 patients. Segmentation performance was evaluated by comparing LV volumes derived by ASM segmentation with different SSMs and those obtained by manual tracing, considered as a reference. A high correlation (r2 > 0.92) was found in all cases, with better results when using the SSM models comprising more than one frame of the cardiac cycle.
Published: 2016

16. Non-invasive treatment planning of tandem coronary artery lesions using an interactive planner for PCI

Author: Jeroen Sonck, Daniele Andreini, Yosuke Miyazaki, Damien Mandry, Université libre de Bruxelles (ULB), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), BIRKER, Juliette, Università degli Studi di Milano = University of Milan (UNIMI)-Università degli Studi di Milano = University of Milan (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), and Cardiology
Subjects: medicine.medical_specialty, medicine.medical_treatment, MEDLINE, [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, Coronary Artery Disease, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 030204 cardiovascular system & hematology, Balloon, [SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Coronary artery disease, 03 medical and health sciences, Percutaneous Coronary Intervention, 0302 clinical medicine, Angioplasty, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, 030212 general & internal medicine, Angioplasty, Balloon, Coronary, Radiation treatment planning, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Percutaneous coronary intervention, medicine.disease, 3. Good health, Treatment Outcome, medicine.anatomical_structure, Conventional PCI, Radiology, Cardiology and Cardiovascular Medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Artery
Abstract: International audience
Published: 2018

17. Path-dependent equations and viscosity solutions in infinite dimension

Author: Andrea Cosso, Nizar Touzi, Fausto Gozzi, Mauro Rosestolato, Salvatore Federico, Laboratoire de Probabilités et Modèles Aléatoires (LPMA), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC), Dipartimento di Economia, Management e Metodi Quantitativi, Universitá di Milano, Department of Economics, Business and Statistics, Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI), Libera Università Internazionale degli Studi Sociali Guido Carli [Roma] (LUISS), Centre de Mathématiques Appliquées - Ecole Polytechnique (CMAP), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Cosso, Andrea, Federico, Salvatore, Gozzi, Fausto, Rosestolato, Mauro, Touzi, Nizar, Cosso, A., Federico, S., Gozzi, F., Rosestolato, M., Touzi, N., Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Università degli Studi di Milano = University of Milan (UNIMI)-Università degli Studi di Milano = University of Milan (UNIMI)
Subjects: Statistics and Probability, Path-dependent stochastic differential equations, Viscosity solution, Markov process, path-dependent partial differential equation, Space (mathematics), partial differential equations in infinite dimension, path-dependent partial differential equations, path-dependent stochastic differential equations, viscosity solutions, 01 natural sciences, viscosity solutions, path-dependent stochastic differential equations, path-dependent partial differential equations, partial differential equations in infinite dimension, 010104 statistics & probability, symbols.namesake, Partial differential equations in infinite dimension, Dimension (vector space), path-dependent stochastic differential equation, FOS: Mathematics, Applied mathematics, Point (geometry), 0101 mathematics, Mathematics, 35D40, Partial differential equation, Probability (math.PR), 010102 general mathematics, Mathematical analysis, Settore MAT/06 - Probabilita' e Statistica Matematica, Path-dependent stochastic differential equation, Path-dependent partial differential equations, [MATH.MATH-PR]Mathematics [math]/Probability [math.PR], Stochastic integration, Viscosity solutions, Viscosity (programming), 60H15, symbols, Statistics, Probability and Uncertainty, 60H30, 35R15, Mathematics - Probability, Path-dependent partial differential equation, Path dependent
Abstract: Path-dependent PDEs (PPDEs) are natural objects to study when one deals with non Markovian models. Recently, after the introduction of the so-called pathwise (or functional or Dupire) calculus (see [15]), in the case of finite-dimensional underlying space various papers have been devoted to studying the well-posedness of such kind of equations, both from the point of view of regular solutions (see e.g. [15, 9]) and viscosity solutions (see e.g. [16]). In this paper, motivated by the study of models driven by path-dependent stochastic PDEs, we give a first well-posedness result for viscosity solutions of PPDEs when the underlying space is a separable Hilbert space. We also observe that, in contrast with the finite-dimensional case, our well-posedness result, even in the Markovian case, applies to equations which cannot be treated, up to now, with the known theory of viscosity solutions., Comment: To appear in the Annals of Probability
Published: 2018

18. One-year outcomes after rapid-deployment aortic valve replacement

Author: Gianluca Polvani, Francesco Alamanni, Christophe Giot, Olivier Bouchot, Günther Laufer, José Aramendi, Marco Solinas, Ugolino Livi, Alfred Kocher, Kim Terp, Bruno K. Podesser, Massimo Massetti, Christopher Young, Mattia Glauber, Jose Arribas, Dipartimento di Ingegneria dell'informazione e scienze matematiche [Siena] (DIISM), Università degli Studi di Siena = University of Siena (UNISI), Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Service d'urologie, and Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: Aortic valve, Male, aortic valve replacement, bioprosthesis, heart valve, hemodynamics, Time Factors, Mean pressure, Hemodynamics, 030204 cardiovascular system & hematology, 0302 clinical medicine, Postoperative Complications, Aortic valve replacement, Risk Factors, Prospective Studies, Registries, Settore MED/23 - CHIRURGIA CARDIACA, ComputingMilieux_MISCELLANEOUS, Aorta, New York Heart Association Class I, Aged, 80 and over, Heart Valve Prosthesis Implantation, Effective orifice area, Middle Aged, Constriction, 3. Good health, Europe, medicine.anatomical_structure, Treatment Outcome, Thoracotomy, Aortic Valve, Heart Valve Prosthesis, Cardiology, Female, Cardiology and Cardiovascular Medicine, Pulmonary and Respiratory Medicine, Reoperation, medicine.medical_specialty, Aortic Valve Insufficiency, Operative Time, 03 medical and health sciences, Internal medicine, medicine, Product Surveillance, Postmarketing, Humans, Heart valve, Adverse effect, Aged, business.industry, Aortic Valve Stenosis, Recovery of Function, medicine.disease, Sternotomy, Surgery, 030228 respiratory system, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: OBJECTIVE: The goals of rapid-deployment aortic valve replacement include facilitation of minimally invasive surgery and reduced aortic crossclamp time. We report the short-term outcomes of a series of 493 patients undergoing rapid-deployment aortic valve replacement with the EDWARDS INTUITY valve system (Edwards Lifesciences, LLC, Irvine, Calif).METHODS: Assessing Standard oF Care and Clinical Outcomes UsiNg the EDWARDS INTUITY VAlve SysTem in a European multI-center, Active, pOst-market surveillaNce Study was a prospective, multicenter (n = 26) European registry designed to evaluate the safety and performance of the valve system. During rapid-deployment aortic valve replacement, device technical success and crossclamp time were assessed. Procedural outcomes, hemodynamic performance, and various adverse events and clinical outcomes were evaluated up to 2 years.RESULTS: Between 2012 and 2014, 493 of 517 enrolled patients successfully received implants with the study valve (95.4% technical success). Mean crossclamp times for 163 full sternotomies, 128 mini-upper sternotomies, and 36 right anterior thoracotomies isolated aortic valve replacements were 47.3, 52.0, and 73.3 minutes, respectively. Mean follow-up was 1.8 years, with 870 total patient-years of follow-up. Mean effective orifice area increased from 0.72 (baseline) to 1.88 cm2, and mean pressure gradient decreased from 47.6 to 9.6 mm Hg (1 year). Mean effective orifice area index increased (0.39-1.01 cm2/m2), and 28 of 287 patients (9.8%) exhibited severe prosthesis-patient mismatch at 1 year. After 1 year, 68.1% and 21.7% of patients were in New York Heart Association class I and II, respectively. Freedom from death, major bleeding, major perivalvular leak, reoperation, and device explant at 1 year were 0.935, 0.939, 0.976, 0.975, and 0.983, respectively.CONCLUSIONS: These results demonstrate commendable safety and performance of the test valve system over the short term in a broad European setting.
Published: 2018

19. Do we need a holistic approach for the design of secure IoT systems?

Author: Giorgio Di Natale, Thomas Pöppelmann, Mauro Conti, Nele Mentens, Annelie Heuser, Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano = University of Milan (UNIMI)-Università degli Studi di Milano = University of Milan (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Test and dEpendability of microelectronic integrated SysTems (TEST), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Threat Analysis and Mitigation for Information Security (TAMIS), Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-LANGAGE ET GÉNIE LOGICIEL (IRISA-D4), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Infineon Technologies AG [München], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), TEST (TEST), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS)-Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), and Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)
Subjects: Cloud computing security, Computer science, 02 engineering and technology, Computer security model, Computer security, computer.software_genre, Security information and event management, 020202 computer hardware & architecture, Security engineering, [INFO.INFO-CR]Computer Science [cs]/Cryptography and Security [cs.CR], Security service, Software security assurance, 0202 electrical engineering, electronic engineering, information engineering, Security through obscurity, Security convergence, 020201 artificial intelligence & image processing, computer
Abstract: International audience; In this paper, four cryptography and security experts point out to future research directions in internet-of-things (IoT) security. Coming from different research domains, the experts address a broad range of issues related to IoT security. In preparation to a panel discussion at the International Workshop on Malicious Software and Hardware in the Internet of Things (MalIoT), they indicate which aspects are important in the design of secured IoT systems, and to which extent we need a holistic approach that integrates security measures at all levels of design abstraction.
Published: 2017

20. Exertional dyspnoea in cardiorespiratory disorders: the clinical use of cardiopulmonary exercise testing

Author: Pierantonio Laveneziana, Piergiuseppe Agostoni, Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service des Explorations Fonctionnelles de la Respiration, de l'Exercice et de la Dyspnée - R3S', Pôle PRAGUES, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), University of Milan, HAL-UPMC, Gestionnaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Explorations Fonctionnelles de la Respiration, de l’Exercice et de la Dyspnée [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli Studi di Milano = University of Milan (UNIMI)-Università degli Studi di Milano = University of Milan (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Università degli Studi di Milano = University of Milan (UNIMI), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Pulmonary and Respiratory Medicine, Pediatrics, medicine.medical_specialty, Pulmonary disease, 030204 cardiovascular system & hematology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Risk Factors, Humans, Medicine, Exercise, Lung, lcsh:RC705-779, business.industry, Respiration, Cardiopulmonary exercise testing, Cardiorespiratory fitness, lcsh:Diseases of the respiratory system, Exertional dyspnoea, 3. Good health, Dyspnea, 030228 respiratory system, Exercise Test, Physical therapy, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business
Abstract: International audience; Is dyspnoea worth documenting and accurately assessing? The answer is undoubtedly yes, for at least the following reasons. 1) Activity-related dyspnoea is usually the earliest and most troublesome complaint for which patients with cardiopulmonary diseases seek medical attention. 2) This symptom progresses relentlessly as the underlying disease advances, leading invariably to avoidance of activity with consequent skeletal muscle deconditioning and an impoverished quality of life. 3) It is estimated that up to a quarter of the general population and half of severely ill patients are affected by it. 4) Dyspnoea is also an important predictor of quality of life, exercise tolerance and mortality in various conditions. In patients with chronic obstructive pulmonary disease (COPD), it has been shown to be a better predictor of mortality than forced expiratory volume in 1 s. In patients with heart disease referred for clinical exercise testing, it is a better predictor of mortality than angina. 5) Dyspnoea is also associated with decreased functional status and worse psychological health in older individuals living at home. 6) It is also a factor in the low adherence to exercise training programmes in sedentary adults and in patients with COPD. 7) The effective management of exertional dyspnoea remains a major challenge for caregivers and modern treatment strategies that are based on attempts to reverse the underlying chronic condition are only partially successful [1–7].
Published: 2016

21. Prognostic value of cardiopulmonary exercise testing in Idiopathic Dilated Cardiomyopathy

Author: Damiano Magrì, Concetta Di Nora, Elena Zambon, Davide Stolfo, Piergiuseppe Agostoni, Giulia Barbati, Andrea Di Lenarda, Marco Merlo, Emanuela Berton, Cosimo Carriere, Stefania Paolillo, Annamaria Iorio, Antonio Cannatà, Gaia Cattadori, Marco Confalonieri, Gianfranco Sinagra, Sinagra, Gianfranco, Iorio, Annamaria, Merlo, Marco, Cannatà, Antonio, Stolfo, Davide, Zambon, Elena, DI NORA, Concetta, Paolillo, Stefania, Barbati, Giulia, Berton, Emanuela, Carriere, Cosimo, Magrì, Damiano, Cattadori, Gaia, Confalonieri, Marco, DI LENARDA, Andrea, Agostoni, Piergiuseppe, Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), University of Milan, Harvard Medical School [Boston] (HMS), Dpt di Scienze Cardiovascolari [Milano], and Centro Cardiologico Monzino, IRCCS
Subjects: Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], heart failure, 030204 cardiovascular system & hematology, prognostic risk stratification, Electrocardiography, 0302 clinical medicine, Interquartile range, 030212 general & internal medicine, Prospective cohort study, Heart transplantation, education.field_of_study, Medicine (all), Area under the curve, Idiopathic Dilated Cardiomyopathy, Middle Aged, Prognosis, 3. Good health, cardiology and cardiovascular medicine, Italy, Cardiology, Female, Cardiology and Cardiovascular Medicine, Anaerobic exercise, circulatory and respiratory physiology, cardiopulmonary exercise testing, idiopathic dilated cardiomyopathy, medicine (all), Adult, Cardiomyopathy, Dilated, medicine.medical_specialty, Prognostic risk stratification, Population, Heart failure, 03 medical and health sciences, Internal medicine, Idiopathic dilated cardiomyopathy, medicine, Humans, education, Retrospective Studies, business.industry, medicine.disease, Cardiopulmonary exercise testing, Exercise Test, business, human activities
Abstract: International audience; Background: Although cardiopulmonary exercise testing (CPET) is considered as animportant tool in risk stratification of patients with heart failure (HF), prognostic data in the specific setting of Idiopathic Dilated Cardiomyopathy (iDCM) are still undetermined. The aim of the study was to test the prognostic value of CPET in a large cohort of iDCM patients. Methods and results: We analyzed 381 iDCM patients who consecutively performed CPET. The study end-point was a composite of cardiovascular death/urgent heart transplantation (CVD/HTx). In the overall population the average values of peak oxygen consumption (peak VO2/kg) and percent-predicted peak VO2 (peak VO2%) were 17.1 +/- 5.1 ml/kg/min and 59 +/- 15%, respectively. Mean VE/VCO2 slope was 29.8 +/- 6.1. During a median follow-up of 47 months (interquartile range 23-84), 83 patients experienced CVD/HTx. Peak VO2% (Area Under the Curve [AUC] 0.74; 95% CI 0.71-0.85, p < 0.001) and VE/VCO2 slope (AUC 0.78; 95% CI 0.74-0.84, p < 0.001) were more accurate in predicting CVD/HTx compared to peak VO2/kg (AUC 0.60; 95% CI 0.54-0.68, p = 0.003) (p < 0.001 for both comparisons). The most accurate threshold values for outcome prediction in our iDCM cohort were
Published: 2016

22. Exertional dyspnoea in chronic heart failure: the role of the lung and respiratory mechanical factors

Author: Pierantonio Laveneziana, Piergiuseppe Agostoni, Bruno-Pierre Dubé, Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano = University of Milan (UNIMI)-Università degli Studi di Milano = University of Milan (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Università degli Studi di Milano = University of Milan (UNIMI), Neurophysiologie Respiratoire Expérimentale et Clinique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), University of Milan, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service des Explorations Fonctionnelles de la Respiration, de l'Exercice et de la Dyspnée - R3S', Pôle PRAGUES, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Explorations Fonctionnelles de la Respiration, de l’Exercice et de la Dyspnée [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and HAL-UPMC, Gestionnaire
Subjects: Pulmonary and Respiratory Medicine, Inotrope, medicine.medical_specialty, Hemodynamics, Respiratory physiology, Disease, 030204 cardiovascular system & hematology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Risk Factors, Internal medicine, medicine, Humans, Intensive care medicine, Exercise, Lung, Tidal volume, Heart Failure, lcsh:RC705-779, Exercise Tolerance, business.industry, lcsh:Diseases of the respiratory system, medicine.disease, Prognosis, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine.anatomical_structure, Dyspnea, 030228 respiratory system, Heart failure, Chronic Disease, Breathing, Cardiology, Disease Progression, Respiratory Mechanics, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business
Abstract: Exertional dyspnoea is among the dominant symptoms in patients with chronic heart failure and progresses relentlessly as the disease advances, leading to reduced ability to function and engage in activities of daily living. Effective management of this disabling symptom awaits a better understanding of its underlying physiology.Cardiovascular factors are believed to play a major role in dyspnoea in heart failure patients. However, despite pharmacological interventions, such as vasodilators or inotropes that improve central haemodynamics, patients with heart failure still complain of exertional dyspnoea. Clearly, dyspnoea is not determined by cardiac factors alone, but likely depends on complex, integrated cardio-pulmonary interactions.A growing body of evidence suggests that excessively increased ventilatory demand and abnormal “restrictive” constraints on tidal volume expansion with development of critical mechanical limitation of ventilation, contribute to exertional dyspnoea in heart failure. This article will offer new insights into the pathophysiological mechanisms of exertional dyspnoea in patients with chronic heart failure by exploring the potential role of the various constituents of the physiological response to exercise and particularly the role of abnormal ventilatory and respiratory mechanics responses to exercise in the perception of dyspnoea in patients with heart failure.
Published: 2016

23. Reciprocal repression between P53 and TCTP

Author: Salvatore Pece, Jessika Wynendaele, Jean-Christophe Marine, Daniela Tosoni, Johan Hoebeke, Rajesh Vyas, Ivan Nicola Colaluca, Robert Amson, Pier Paolo Di Fiore, Sylvie Rodrigues-Ferreira, Giuseppe Viale, Alexandra Lespagnol, Adam Telerman, Giovanni Mazzarol, Olivier Chaloin, Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano [Milano] (UNIMI), CHU Pontchaillou [Rennes], Division of Pathology and Laboratory Medicine, European Institute of Oncology [Milan] (ESMO), Università degli Studi di Milano [Milano] (UNIMI)-European Institute of Oncology [Milan] (ESMO), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), Centre de Génétique Humaine, Université Catholique de Louvain = Catholic University of Louvain (UCL), Università degli studi di Milano [Milano], Università degli studi di Milano [Milano]-European Institute of Oncology [Milan] (ESMO), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain (UCL), and European Institute of Oncology
Subjects: [SDV]Life Sciences [q-bio], Apoptosis, Breast Neoplasms, Nerve Tissue Proteins, [SDV.CAN]Life Sciences [q-bio]/Cancer, Haploinsufficiency, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, General Biochemistry, Genetics and Molecular Biology, Mice, 03 medical and health sciences, 0302 clinical medicine, Translationally-controlled tumor protein, Biomarkers, Tumor, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Promoter Regions, Genetic, 030304 developmental biology, Feedback, Physiological, Mice, Knockout, Regulation of gene expression, Mice, Inbred BALB C, [SDV.GEN]Life Sciences [q-bio]/Genetics, 0303 health sciences, Gene knockdown, Mammary tumor, Ubiquitination, Membrane Proteins, Tumor Protein, Translationally-Controlled 1, Proto-Oncogene Proteins c-mdm2, General Medicine, HCT116 Cells, Prognosis, 3. Good health, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, Proteolysis, Cancer cell, Neoplastic Stem Cells, NUMB, biology.protein, Cancer research, Mdm2, Female, Translationally controlled tumour protein, Tumor Suppressor Protein p53, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Screening for genes that reprogram cancer cells for the tumor reversion switch identified TCTP (encoding translationally controlled tumor protein) as a crucial regulator of apoptosis. Here we report a negative feedback loop between P53 and TCTP. TCTP promotes P53 degradation by competing with NUMB for binding to P53-MDM2-containing complexes. TCTP inhibits MDM2 auto-ubiquitination and promotes MDM2-mediated ubiquitination and degradation of P53. Notably, Tctp haploinsufficient mice are sensitized to P53-dependent apoptosis. In addition, P53 directly represses TCTP transcription. In 508 breast cancers, high-TCTP status associates with poorly differentiated, aggressive G3-grade tumors, predicting poor prognosis (P < 0.0005). Tctp knockdown in primary mammary tumor cells from ErbB2 transgenic mice results in increased P53 expression and a decreased number of stem-like cancer cells. The pharmacological compounds sertraline and thioridazine increase the amount of P53 by neutralizing TCTP's action on the MDM2-P53 axis. This study links TCTP and P53 in a previously unidentified regulatory circuitry that may underlie the relevance of TCTP in cancer.
Published: 2011

24. Uninterrupted rivaroxaban vs. uninterrupted vitamin K antagonists for catheter ablation in non-valvular atrial fibrillation

Author: L. Eugene Fields, Gerald V. Naccarelli, Christian de Chillou, Burkhard J. Hügl, Richard Balasubramaniam, Andrea Natale, Riccardo Cappato, Darryl S. Wells, Johan Vijgen, Susanne Hess, Stefan H. Hohnloser, George Juang, David J. Wilber, Francis E. Marchlinski, C.S. Ma, D. Wyn Davies, Jim Xiang, Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Second Arrhytmia and EP Unit (SA and EP Unit - BERGAMO), GAVAZZENI Hospital, Section of Cardiac Electrophysiology (SCE - PHILADELPHIA), Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Division of Clinical Electrophysiology (DCE - FRANKFURT), J.W.Goethe University Hospital, Heart and Vascular Institute (HVI - HERSHEY), Pennsylvania State University (Penn State), Penn State System-Penn State System, Biostatistics and Programming (Biostat Program - Janssen Research), Janssen Research & Development, Department of Cardiology, Loyola University [Chicago], Cardiology Division (Cardio Div - BEIJING), Capital Medical University, Beijing, Medical Affairs (MA - BAYER), Bayer HealthCare Pharmaceuticals Inc [Whippany], Cardiac Electrophysiology (Card Electro - SEATTLE), Swedish Heart and Vascular Institute, Heart and Arrhythmia, Heart and Arrhythmia Care of New York (HACNW), Division of Cardiac Electrophysiology (Div Card Elec - HASSELT), JESSA HOSPITALS, Department of Cardiology and Rhythmology (Dep Card Rhythmo - NEUWIED), Marienhaus Klinikum St Elisabeth (MK St Elisabeth), Department of Cardiology (Dep Cardio - BOURNEMOUTH), Royal Bournemouth Hospital, Service de Cardiologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Waller Department of Cardiology (Waller Dep Cardiol - LONDON), Imperial College London, Department of Medical and Scientific Affairs, Janssen EMEA, Texas Cardiac Arrhythmia Institute (Texas Card Arrh Ins - AUSTIN), and St David's Medical Center (St D Med Center - AUSTIN)
Subjects: Male, Reoperation, medicine.medical_specialty, Vitamin K, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Operative Time, Activated clotting time, Blood Loss, Surgical, Catheter ablation, Drug Administration Schedule, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Rivaroxaban, Recurrence, Internal medicine, Thromboembolism, Atrial Fibrillation, medicine, Clinical endpoint, Humans, Single-Blind Method, Myocardial infarction, Prospective Studies, Stroke, medicine.diagnostic_test, Surrogate endpoint, business.industry, Atrial fibrillation, Middle Aged, medicine.disease, 3. Good health, Treatment Outcome, Pulmonary Veins, Anesthesia, Cardiology, Catheter Ablation, Oral anticoagulant, Female, Cardiology and Cardiovascular Medicine, business, Uninterrupted, Anti-Arrhythmia Agents, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug, Factor Xa Inhibitors
Abstract: Aims VENTURE-AF is the first prospective randomized trial of uninterrupted rivaroxaban and vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (NVAF) undergoing catheter ablation (CA). Methods and results Trial size was administratively set at 250, the protocol-specified target. Events were independently and blindly adjudicated. We randomly assigned 248 NVAF patients to uninterrupted rivaroxaban (20 mg once-daily) or to an uninterrupted VKA prior to CA and for 4 weeks afterwards. The primary endpoint was major bleeding events after CA. Secondary endpoints included thromboembolic events (composite of stroke, systemic embolism, myocardial infarction, and vascular death) and other bleeding or procedure-attributable events. Patients were 59.5 ± 10 years of age, 71% male, 74% paroxysmal AF, and had a CHA2DS2-VASc score of 1.6. The average total heparin dose used to manage activated clotting time (ACT) was slightly higher (13 871 vs. 10 964 units; P < 0.001) and the mean ACT level attained slightly lower (302 vs. 332 s; P < 0.001) in rivaroxaban and VKA arms, respectively. The incidence of major bleeding was low (0.4%; 1 major bleeding event). Similarly, thromboembolic events were low (0.8%; 1 ischemic stroke and 1 vascular death). All events occurred in the VKA arm and all after CA. The number of any adjudicated events (26 vs. 25), any bleeding events (21 vs. 18), and any other procedure-attributable events (5 vs. 5) were similar. Conclusion In patients undergoing CA for AF, the use of uninterrupted oral rivaroxaban was feasible and event rates were similar to those for uninterrupted VKA therapy. Name of the Trial Registry Clinicaltrials.gov trial registration number is [NCT01729871][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01729871&atom=%2Fehj%2F36%2F28%2F1805.atom
Published: 2015

25. A structure theorem for $SU_C(2)$ and the moduli of pointed rational curves

Author: Michele Bolognesi, Alberto Alzati, Dipartimento di Matematica 'F. Enriques', Universit' degli Studi di Milano, Department of Mathematics 'Federigo Enriques', Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI), Institut de Recherche Mathématique de Rennes (IRMAR), AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Department of Mathematics 'Federigo Enriques, Università degli studi di Milano [Milano]-Università degli studi di Milano [Milano], Institut de Recherche Mathématique de Rennes ( IRMAR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -AGROCAMPUS OUEST-École normale supérieure - Rennes ( ENS Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National des Sciences Appliquées ( INSA ) -Université de Rennes 2 ( UR2 ), Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ), Università degli Studi di Milano = University of Milan (UNIMI)-Università degli Studi di Milano = University of Milan (UNIMI), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École normale supérieure - Rennes (ENS Rennes)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-INSTITUT AGRO Agrocampus Ouest, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)
Subjects: Algebra and Number Theory, 010102 general mathematics, Mathematical analysis, 01 natural sciences, Moduli, [ MATH.MATH-AG ] Mathematics [math]/Algebraic Geometry [math.AG], Moduli of algebraic curves, 14H60, 14H10, 0103 physical sciences, 010307 mathematical physics, Geometry and Topology, [MATH.MATH-AG]Mathematics [math]/Algebraic Geometry [math.AG], 0101 mathematics, ComputingMilieux_MISCELLANEOUS, Mathematics, Structured program theorem
Abstract: Let S U C ( 2 ) \mathcal {SU}_C(2) be the moduli space of rank 2 semistable vector bundles with trivial determinant on a smooth complex algebraic curve C C of genus g > 1 g>1 . We assume C C nonhyperellptic if g > 2 g>2 . In this paper we construct large families of pointed rational normal curves over certain linear sections of S U C ( 2 ) \mathcal {SU}_C(2) . This allows us to give an interpretation of these subvarieties of S U C ( 2 ) \mathcal {SU}_C(2) in terms of the moduli space of curves M 0 , 2 g \mathcal {M}_{0,2g} . In fact, there exists a natural linear map S U C ( 2 ) → P g \mathcal {SU}_C(2) \to \mathbb {P}^g with modular meaning, whose fibers are birational to M 0 , 2 g \mathcal {M}_{0,2g} , the moduli space of 2 g 2g -pointed genus zero curves. If g > 4 g>4 , these modular fibers are even isomorphic to the GIT compactification M 0 , 2 g G I T \mathcal {M}_{0,2g}^{GIT} . The families of pointed rational normal curves are recovered as the fibers of the maps that classify extensions of line bundles associated to some effective divisors.
Published: 2015

26. On the infinite-dimensional representation of stochastic controlled systems with delayed control in the diffusion term

Author: Salvatore Federico, Giorgio Fabbri, Centre d'Etudes des Politiques Economiques (EPEE), Université d'Évry-Val-d'Essonne (UEVE), Dipartimento di economia, management e metodi quantitativi, Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI), and Università degli Studi di Milano = University of Milan (UNIMI)-Università degli Studi di Milano = University of Milan (UNIMI)
Subjects: 0209 industrial biotechnology, Mathematical optimization, [QFIN.PM]Quantitative Finance [q-fin]/Portfolio Management [q-fin.PM], jel:C61, Evolution equations in Hilbert space, Control variable, Context (language use), 02 engineering and technology, Stochastic delay differential equations, Dynamic programming, 01 natural sciences, jel:O40, 020901 industrial engineering & automation, Quadratic equation, JEL: C - Mathematical and Quantitative Methods/C.C6 - Mathematical Methods • Programming Models • Mathematical and Simulation Modeling/C.C6.C61 - Optimization Techniques • Programming Models • Dynamic Analysis, Dimension (vector space), JEL: G - Financial Economics/G.G1 - General Financial Markets/G.G1.G11 - Portfolio Choice • Investment Decisions, 0101 mathematics, Representation (mathematics), Mathematics, Series (mathematics), 010102 general mathematics, Stochastic delay differential equations,Evolution equations in Hilbert space,Dynamic programming, Delay differential equation, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, jel:G11, Term (time), Stochastic delay differential equations, Evolution equations in Hilbert space, Dynamic programming, JEL: O - Economic Development, Innovation, Technological Change, and Growth/O.O4 - Economic Growth and Aggregate Productivity/O.O4.O40 - General
Abstract: In the deterministic context a series of well established results allow to reformulate delay differential equations (DDEs) as evolution equations in infinite dimensional spaces. Several models in the theoretical economic literature have been studied using this reformulation. On the other hand, in the stochastic case only few results of this kind are available and only for specific problems. The contribution of the present letter is to present a way to reformulate in infinite dimension a prototype controlled stochastic DDE, where the control variable appears delayed in the diffusion term. As application, we present a model for quadratic risk minimization hedging of European options with execution delay and a time-to-build model with shock. Some comments concerning the possible employment of the dynamic programming after the reformulation in infinite dimension conclude the letter.
Published: 2014

27. Explicit investment rules with time-to-build and uncertainty

Author: Huyên Pham, René Aïd, Bertrand Villeneuve, Salvatore Federico, Laboratoire de Finance des Marchés d'Energie (FiME Lab), EDF R&D (EDF R&D), EDF (EDF)-EDF (EDF)-CREST-Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Dipartimento di Economia, Management e Metodi Quantitativi, Universitá di Milano, Department of Economics, Business and Statistics, Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI), Centre de Recherche en Économie et Statistique (CREST), Ecole Nationale de la Statistique et de l'Analyse de l'Information [Bruz] (ENSAI)-École polytechnique (X)-École Nationale de la Statistique et de l'Administration Économique (ENSAE Paris)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Probabilités et Modèles Aléatoires (LPMA), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire d'Economie de Dauphine (LEDa), Université Paris Dauphine-PSL, Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-CREST-EDF R&D (EDF R&D), EDF (EDF)-EDF (EDF), and Università degli Studi di Milano = University of Milan (UNIMI)-Università degli Studi di Milano = University of Milan (UNIMI)
Subjects: Economics and Econometrics, Control and Optimization, Comparative statics, delay equations, JEL: E - Macroeconomics and Monetary Economics/E.E2 - Consumption, Saving, Production, Investment, Labor Markets, and Informal Economy/E.E2.E22 - Investment • Capital • Intangible Capital • Capacity, JEL: D - Microeconomics/D.D9 - Intertemporal Choice/D.D9.D92 - Intertemporal Firm Choice, Investment, Capacity, and Financing, 01 natural sciences, FOS: Economics and business, Microeconomics, 010104 statistics & probability, JEL: C - Mathematical and Quantitative Methods/C.C6 - Mathematical Methods • Programming Models • Mathematical and Simulation Modeling/C.C6.C61 - Optimization Techniques • Programming Models • Dynamic Analysis, Demand curve, singular stochastic control, 0502 economics and business, Economics, Econometrics, irreversible investments, 0101 mathematics, Brownian motion, ComputingMilieux_MISCELLANEOUS, Delay equations, Irreversible investments, Optimal capacity, Singular stochastic control, Time-to-build, [QFIN.GN]Quantitative Finance [q-fin]/General Finance [q-fin.GN], Discounting, 050208 finance, Risk aversion, Applied Mathematics, 05 social sciences, Investment (macroeconomics), Mathematical Finance (q-fin.MF), delay equations,optimal capacity,irreversible investments,singular stochastic control,time-to-build,delay equations, time-to-build, Nameplate capacity, [MATH.MATH-PR]Mathematics [math]/Probability [math.PR], Cox–Ingersoll–Ross model, Quantitative Finance - Mathematical Finance, Local volatility, Volatility (finance), optimal capacity
Abstract: International audience; We establish explicit socially optimal rules for an irreversible investment decision with time-to-build and uncertainty. Assuming a price sensitive demand function with a random intercept, we provide comparative statics and economic interpretations for three models of demand (arithmetic Brownian, geometric Brownian, and the Cox-Ingersoll-Ross). Committed capacity, that is, the installed capacity plus the investment in the pipeline, must never drop below the best predictor of future demand, minus two biases. The discounting bias takes into account the fact that investment is paid upfront for future use; the precautionary bias multiplies a type of risk aversion index by the local volatility. Relying on the analytical forms, we discuss in detail the economic effects. For example, the impact of volatility on the optimal investment is negligible in some cases. It vanishes in the CIR model for long delays, and in the GBM model for high discount rates.
Published: 2014

28. Reassessing Vulnerability to Macroeconomic Volatility: a nonstationary panel approach

Author: Clévenot, Mickaël, Mbome, Marie Silvère, Centre d'Economie de l'Université Paris Nord (CEPN), Centre National de la Recherche Scientifique (CNRS)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13), LASER, and Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)
Subjects: Volatilité macroéconomique, JEL: E - Macroeconomics and Monetary Economics/E.E3 - Prices, Business Fluctuations, and Cycles/E.E3.E32 - Business Fluctuations • Cycles, unit root test and panel cointegration, growth, Macroeconomic volatility,growth,cross-section dependence,unit root test and panel cointegration,Volatilité macroéconomique,croissance,interdépendance,test de racine unitaire et cointégration de panel, test de racine unitaire et cointégration de panel, cross-section dependence, Macroeconomic volatility, interdépendance, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, croissance, JEL: F - International Economics/F.F5 - International Relations, National Security, and International Political Economy/F.F5.F54 - Colonialism • Imperialism • Postcolonialism, JEL: O - Economic Development, Innovation, Technological Change, and Growth/O.O4 - Economic Growth and Aggregate Productivity/O.O4.O43 - Institutions and Growth
Abstract: The article examines the sensibility of economic growth to macroeconomic volatility, and the impact of financial development on volatility for a sample of 85 countries and OECD countries over two periods covering 1975 to 2006. In that purpose, we implented nonstationary panel techniques that account for cross-section dependence issue. We checked for the existence of a cointegrating relationship between variables. Finally we estimated such relationship using the Augmented mean group (AMG) method. We confirm the Ramey (1995) findings of the negative correlation between output growth and volatility for the full sample and the subsample of OECD countries, however our results are stronger for OECD countries. Moreover accounting for the interaction between volatility and financial development leads to stronger results. Indeed the interaction seems to impact positively on growth, but at the same times, it seems to magnify vulnerability to shocks., L'objet principal de ce travail consiste à mesurer la sensibilité de la croissance à la volatilité macroéconomique sur un panel de 85 pays OCDE et Non- OCDE sur la période 1975 2006. Nous mobilisons les techniques des panels non-stationnaires et de la cointégration de panel (méthode AMG) afin d'identifier avec précision la vulnérabilité de la croissance à la volatilité macroéconomique. Avec un cadre méthodologue plus solide, nous retrouvons les résultats établis par Ramey & Ramey (1995). Ainsi, l'ensemble de l'échantillon décrit une relation négative entre la volatilité et la croissance. Les résultats sont plus nets pour les pays de l'OCDE. La crise en compte des interactions conduit à nuancer les résultats. En effet, l'interaction entre développement financier et volatilité semble jouer un rôle positif sur la croissance. Mais de l'autre côté, la sensibilité de la croissance à la volatilité est accrue.
Published: 2014

29. Characterization of the Optimal Boundaries in Reversible Investment Problems

Author: Huyên Pham, Salvatore Federico, Laboratoire de Probabilités et Modèles Aléatoires (LPMA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Dipartimento di Economia, Management e Metodi Quantitativi, Universitá di Milano, Department of Economics, Business and Statistics, Università degli Studi di Milano = University of Milan (UNIMI)-Università degli Studi di Milano = University of Milan (UNIMI), Centre de Recherche en Économie et Statistique (CREST), Ecole Nationale de la Statistique et de l'Analyse de l'Information [Bruz] (ENSAI)-École polytechnique (X)-École Nationale de la Statistique et de l'Administration Économique (ENSAE Paris)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC)
Subjects: Optimization, Mathematical optimization, Reversible investment, Control and Optimization, Optimization problem, Viscosity solution, Boundary (topology), Bellman equation, Smooth-fit, FOS: Mathematics, Singular stochastic control, Investments, ComputingMilieux_MISCELLANEOUS, Mathematics, Optimal capacity, Stochastic control, MSC: 93E20, 49J40, 49L25, Applied Mathematics, Probability (math.PR), Smooth fit, Function (mathematics), [MATH.MATH-PR]Mathematics [math]/Probability [math.PR], Stochastic control systems, Viscosity solutions, Bounded variation, A priori and a posteriori, Stochastic control systems, Optimal capacity, Viscosity solutions, Investments, Mathematics - Probability
Abstract: International audience; This paper studies a reversible investment problem where a social planner aims to control its capacity production in order to fit optimally the random demand of a good. Our model allows for general diffusion dynamics on the demand as well as general cost functional. The resulting optimization problem leads to a degenerate two-dimensional bounded variation singular stochastic control problem, for which explicit solution is not available in general and the standard verification approach cannot be applied a priori. We use a direct viscosity solutions approach for deriving some features of the optimal free boundary function and for displaying the structure of the solution. In the quadratic cost case, we are able to prove a smooth fit C-2 property, which gives rise to a full characterization of the optimal boundaries and value function.
Published: 2014

30. Dynamics of Ecological Communities Following Current Retreat of Glaciers

Author: Silvio Marta, Mauro Gobbi, Diego Fontaneto, Jérôme Poulenard, Andrea Zerboni, Alessia Guerrieri, Gentile Francesco Ficetola, Wilfried Thuiller, Roberto Ambrosini, Marco Caccianiga, Università degli Studi di Milano [Milano] (UNIMI), Museo delle Scienze, CNR Water Research Institute (IRSA), Consiglio Nazionale delle Ricerche (CNR), Department of Earth Sciences 'Ardito Desio', Environnements, Dynamiques et Territoires de la Montagne (EDYTEM), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Laboratoire d'Ecologie Alpine (LECA ), and Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
Subjects: 0106 biological sciences, 0303 health sciences, geography.geographical_feature_category, Ecology, Chronosequence, Climate change, Glacier, Ecological succession, 15. Life on land, Community formation, 010603 evolutionary biology, 01 natural sciences, Food web, Current (stream), 03 medical and health sciences, Geography, 13. Climate action, Colonization, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology
Abstract: International audience; Glaciers are retreating globally, and the resulting ice-free areas provide an experimental system for understanding species colonization patterns, community formation, and dynamics. The last several years have seen crucial advances in our understanding of biotic colonization after glacier retreats, resulting from the integration of methodological innovations and ecological theories. Recent empirical studies have demonstrated how multiple factors can speed up or slow down the velocity of colonization and have helped scientists develop theoretical models that describe spatiotemporal changes in community structure. There is a growing awareness of how different processes (e.g., time since glacier retreat, onset or interruption of surface processes, abiotic factors, dispersal, biotic interactions) interact to shape community formation and, ultimately, their functional structure through succession. Here, we examine how these studies address key theoretical questions about community dynamics and show how classical approaches are increasingly being combined with environmental DNA metabarcoding and functional trait analysis to document the formation of multitrophic communities, revolutionizing our understanding of the biotic processes that occur following glacier retreat. Expected final online publication date for the Annual Review of Ecology, Evolution, and Systematics, Volume 52 is November 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Published: 2021

31. 'Stratigraphic, sedimentological and palaeoenvironmental constraints on the rise of the Urgonian platform in the western Swiss Jura' by A. Godet et al. (2010) Sedimentology 57, 1088-1125: Discussion

Author: Conrad, Marc, Clavel, Bernard, Granier, Bruno, Charollais, Jean, Busnardo, Robert, Erba, Elisabetta, Gardin, Silvia, Jan Du Chene, Roger, Decrouez, Danielle, Cherchi, Antonietta, Schroeder, Rolf, Sauvagnat, Jacques, Weidmann, Marc, Domaines Océaniques (LDO), Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Observatoire des Sciences de l'Univers-Institut d'écologie et environnement-Centre National de la Recherche Scientifique (CNRS), Earth and Environmental Sciences, University of Geneva [Switzerland], Section of Geology and Paleontology [Milano], Department of Earth Sciences 'Ardito Desio', Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI), Centre de recherche sur la Paléobiodiversité et les Paléoenvironnements (CR2P), Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC), Dipartimento di Scienze della Terra [Cagliari], Universita degli Studi di Cagliari [Cagliari], Forschungsinstitut Senckenberg, Frankfurt am Main, Forschungsinstitut Senckenberg (SGN), Université de Genève = University of Geneva (UNIGE), Università degli Studi di Milano = University of Milan (UNIMI)-Università degli Studi di Milano = University of Milan (UNIMI), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), and Università degli Studi di Cagliari = University of Cagliari (UniCa)
Subjects: [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2011

32. Effect of curve location on the severity index for adolescent idiopathic scoliosis: a longitudinal cohort study

Author: Jean-Claude Bernard, Raphaël Vialle, Ayman Assi, Jean Dubousset, Fabio Galbusera, Wafa Skalli, Mohammad Karam, Claudio Vergari, Isabelle Courtois, Marco Brayda-Bruno, Tristan Langlais, Kariman Abelin-Genevois, Tito Bassani, Ismat Ghanem, Eric Ebermeyer, Zongshan Hu, Luca Maria Sconfienza, Winnie C.W. Chu, Jack C. Y. Cheng, Institut de Biomécanique Humaine Georges Charpak (IBHGC), Université Sorbonne Paris Nord-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM), Department of Orthopaedic Surgery, Université Catholique de Louvain = Catholic University of Louvain (UCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), The Chinese University of Hong Kong [Hong Kong], Université Saint-Joseph de Beyrouth (USJ), IRCCS Istituto Ortopedico Galeazzi, Università degli Studi di Milano [Milano] (UNIMI), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Service de pédiatrie orthopédique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], Scoliosis, 030218 nuclear medicine & medical imaging, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Lumbar, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Longitudinal Studies, Child, Pelvis, Retrospective Studies, Neuroradiology, Cobb angle, business.industry, General Medicine, medicine.disease, Spine, Confidence interval, Treatment Outcome, medicine.anatomical_structure, Radiology Nuclear Medicine and imaging, 030220 oncology & carcinogenesis, Predictive value of tests, Cohort, Disease Progression, Sciences du vivant, Radiology, business
Abstract: Adolescent idiopathic scoliosis (AIS) is the most common spinal disorder in children. A severity index was recently proposed to identify the stable from the progressive scoliosis at the first standardized biplanar radiographic exam. The aim of this work was to extend the validation of the severity index and to determine if curve location influences its predictive capabilities. AIS patients with Cobb angle between 10° and 25°, Risser 0–2, and no previous treatment were included. They underwent standing biplanar radiography and 3D reconstruction of the spine and pelvis, which allowed to calculate their severity index. Patients were grouped by curve location (thoracic, thoracolumbar, lumbar). Patients were followed up until skeletal maturity (Risser ≥ 3) or brace prescription. Their outcome was compared to the prediction made by the severity index. In total, 205 AIS patients were included; 82% of them (155/189, 95% confidence interval [74–90%]) were correctly classified by the index, while 16 patients were unclassified. Positive predictive ratio was 78% and negative predictive ratio was 86%. Specificity (78%) was not significantly affected by curve location, while patients with thoracic and lumbar curves showed higher sensitivity (≥ 89%) than those with thoracolumbar curves (74%). In this multicentric cohort of 205 patients, the severity index was used to predict the risk of progression from mild to moderate scoliosis, with similar results of typical major curve types. This index represents a novel tool to aid the clinician and the patient in the modulation of the follow-up and, for progressive patients, their decision for brace treatment. • The severity index of adolescent idiopathic scoliosis has the potential to detect patients with progressive scoliosis as early as the first exam. • Out of 205 patients, 82% were correctly classified as either stable or progressive by the severity index. • The location of the main curve had small effect on the predictive capability of the index.
Published: 2021

33. Tackling unresolved questions in forest ecology: The past and future role of simulation models

Author: Alessio Collalti, Kirsten Thonicke, Fanny Langerwisch, Friedrich J. Bohn, Manfred J. Lexer, Xavier Morin, Edna Rödig, Heike Lischke, Franziska Taubert, Isabelle Maréchaux, Martin Gutsch, Giorgio Vacchiano, Boris Sakschewski, Anja Rammig, Christopher P. O. Reyer, Harald Bugmann, Andreas Huth, Rupert Seidl, Mateus Dantas de Paula, Rico Fischer, Botanique et Modélisation de l'Architecture des Plantes et des Végétations (UMR AMAP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Palacky University Olomouc, Osnabrück University, Helmholtz Zentrum für Umweltforschung = Helmholtz Centre for Environmental Research (UFZ), German Centre for Integrative Biodiversity Research (iDiv), Institute of Terrestrial Ecosystems (ITES), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Université Paul-Valéry - Montpellier 3 (UPVM)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Potsdam Institute for Climate Impact Research (PIK), University of Natural Resources and Life Sciences (BOKU), University of Tuscia, Senckenberg Biodiversity and Climate Research Centre (SBiK-F), Goethe-Universität Frankfurt am Main-Senckenberg – Leibniz Institution for Biodiversity and Earth System Research - Senckenberg Gesellschaft für Naturforschung, Leibniz Association-Leibniz Association, Swiss Federal Institute for Forest, Snow and Landscape Research WSL, Technical University of Munich (TUM), Università degli Studi di Milano [Milano] (UNIMI), COST Action FP1304 PROFOUND, German Federal Ministry of Science and Education. Grant Number: 01LS1711A, Austrian Science Fund. Grant Number: Y895‐B25, ANR-10-LABX-0025,CEBA,CEnter of the study of Biodiversity in Amazonia(2010), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Universität Osnabrück - Osnabrück University, Université Paul-Valéry - Montpellier 3 (UPVM)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Universität für Bodenkultur Wien = University of Natural Resources and Life [Vienne, Autriche] (BOKU), Università degli studi della Tuscia [Viterbo], Università degli Studi di Milano = University of Milan (UNIMI), and Lehrstuhl für Ökosystemdynamik und Waldmanagement in Gebirgslandschaften
Subjects: 0106 biological sciences, Reviews, Context (language use), Review, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, 010603 evolutionary biology, 01 natural sciences, Dynamic global vegetation model, 03 medical and health sciences, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, Forest ecology, ddc:630, Ecology, Evolution, Behavior and Systematics, QH540-549.5, 030304 developmental biology, Nature and Landscape Conservation, Pace, Gap model, 0303 health sciences, Forest dynamics, Ecology, business.industry, Forest modelling, Simulation modeling, Environmental resource management, Species distribution model, Vegetation, 15. Life on land, [SDV.BV.BOT]Life Sciences [q-bio]/Vegetal Biology/Botanics, ddc, Geography, 13. Climate action, Complementarity (molecular biology), [SDE.BE]Environmental Sciences/Biodiversity and Ecology, business
Abstract: Understanding the processes that shape forest functioning, structure, and diversity remains challenging, although data on forest systems are being collected at a rapid pace and across scales. Forest models have a long history in bridging data with ecological knowledge and can simulate forest dynamics over spatio‐temporal scales unreachable by most empirical investigations.We describe the development that different forest modelling communities have followed to underpin the leverage that simulation models offer for advancing our understanding of forest ecosystems.Using three widely applied but contrasting approaches – species distribution models, individual‐based forest models, and dynamic global vegetation models – as examples, we show how scientific and technical advances have led models to transgress their initial objectives and limitations. We provide an overview of recent model applications on current important ecological topics and pinpoint ten key questions that could, and should, be tackled with forest models in the next decade.Synthesis. This overview shows that forest models, due to their complementarity and mutual enrichment, represent an invaluable toolkit to address a wide range of fundamental and applied ecological questions, hence fostering a deeper understanding of forest dynamics in the context of global change., Forest models can help understanding the processes that shape forest functioning, structure and diversity, since they can can simulate forest dynamics over spatio‐temporal scales unreachable by most empirical investigations. Here we describe the development of three widely applied but contrasting forest mo−delling approaches — species distribution models, individual‐based models and dynamic global vegetation models. We provide an overview of recent model applications and pinpoint ten key questions that could, and should, be tackled with forest models in the next decade.
Published: 2021

34. Mitral valve patient-specific finite element modeling from 3-D real time echocardiography: a potential new tool for surgical planning

Author: Votta, Emiliano, Arnoldi, Alice, Invernizzi, Alice, Ponzini, Raffaele, Veronesi, Federico, Tamborini, Gloria, Pepi, Mauro, Alamanni, Francesco, Redaelli, Alberto, Caiani, Enrico G., Department of Bioengineering [Politecnico Milano], Politecnico di Milano [Milan] (POLIMI), Consorzio Interuniversitario Lombardo per l'Elaborazione Automatica [Milano] (CILEA), CILEA, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), and Session 02 : Hemodynamics and Computational Fluid Dynamics
Subjects: [INFO.INFO-IM]Computer Science [cs]/Medical Imaging
Abstract: International audience; Mitral valve (MV) physiopathological function and the effects of surgical repair can be studied through finite element models (FEMs). However, this approach assumes idealized morphology and boundary conditions limiting the analysis to paradigmatic scenarios and precluding patient-specific surgical planning. To overcome this limitation, we integrated into a MV FEM the patient-specific information about leaflets, annulus and papillary muscles geometry and dynamics, obtained from real-time 3D echocardiography. An ad-hoc web platform was created to facilitate FEM development from remote users, and grant access to parallel computing facilities. This approach was tested simulating MV closure in three normal subjects. Modelled valvular dynamics and quantitative results were consistent with experimental findings from literature. FEMs implementation required about 6 min, while simulations required about 7.5 hours on 32 parallel CPUs. Our approach appears reliable, reproducible and reasonably fast and may constitute the basis for the development of patient-specific tools for MV surgery. Introduction
Published: 2009

35. Towards improving the MITC6 triangular shell element

Author: L. Beirão da Veiga, I. Paris Suarez, Dominique Chapelle, Dipartimento di Matematica 'F. Enriques', Universit' degli Studi di Milano, Department of Mathematics 'Federigo Enriques', Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI), Modeling, analysis and control in computational structural dynamics (MACS), Inria Paris-Rocquencourt, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), BEIRAO DA VEIGA, L, Paris, I, Chapelle, D, and Università degli Studi di Milano = University of Milan (UNIMI)-Università degli Studi di Milano = University of Milan (UNIMI)
Subjects: Engineering, Shell (structure), 02 engineering and technology, Bending, Bilinear form, 01 natural sciences, Displacement (vector), Strain energy, Triangular MITC element, 0203 mechanical engineering, Shell, General Materials Science, Boundary value problem, 0101 mathematics, Boundary element method, Civil and Structural Engineering, business.industry, Mechanical Engineering, Mathematical analysis, Structural engineering, Stabilization, Finite element method, Computer Science Applications, Spurious mode, 010101 applied mathematics, 020303 mechanical engineering & transports, Locking, Modeling and Simulation, Mixed formulation, business, [MATH.MATH-NA]Mathematics [math]/Numerical Analysis [math.NA]
Abstract: International audience; Effective triangular shell elements are of utmost interest in engineering practice, and the MITC6a element - a 6 node quadratic general shell element of the MITC family - has been shown to significantly reduce the locking phenomena arising in bending dominated behaviours. However, for some specific combinations of midsurface geometry and boundary conditions, the MITC6a element features some non-physical displacement modes with vanishing membrane strain energy. This phenomenon is thoroughly analyzed, and a remedy based on a stabilized bilinear form is proposed. Detailed numerical tests are included and the results demonstrate the good performance of the proposed method both for membrane and bending dominated problems.
Published: 2007

36. Information Security and Privacy – Challenges and Outlook

Author: Furnell, S., Haskell-Dowland, P., Agrawal, M., Baskerville, R., Basu, A., Bishop, M., Cuellar, J., Foresti, S., Futcher, L., Gal-Oz, N., Herath, T., Damsgaard Jensen, C., Johnston, A., Joosen, W., Livraga, G., Lopez, J., Marsh, S., Martinelli, F., Massacci, F., Pasic, A., Schinagl, S., Shahim, A., Thomson, K.-L., Vaidya, J., Vance, T., Warkentin, M., Goedicke, Michael, Neuhold, Erich, Rannenberg, Kai, Computer Systems, Network Institute, Accounting, School of Computer and Security Science, EDITH COWAN UNIVERSITY, School of Computer Science and IT, University of Nottingham, UK (UON), University of South Florida [Tampa] (USF), Georgia State University, University System of Georgia (USG), University of Sussex, University of California [Davis] (UC Davis), University of California, University of Passau, Università degli Studi di Milano [Milano] (UNIMI), Nelson Mandela Metropolitan University [Port Elizabeth, South Africa], Sapir Academic College, Brock University [Canada], Technical University of Denmark [Lyngby] (DTU), University of Alabama [Tuscaloosa] (UA), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Universidad de Málaga [Málaga] = University of Málaga [Málaga], University of Ontario Institute of Technology (UOIT), Consiglio Nazionale delle Ricerche [Roma] (CNR), University of Trento [Trento], Atos Origin sae, Vrije Universiteit Amsterdam [Amsterdam] (VU), Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), Rutgers University [Newark], Rutgers University System (Rutgers), Temple University [Philadelphia], Pennsylvania Commonwealth System of Higher Education (PCSHE), Mississippi State University [Mississippi], VU University Amsterdam, Goedicke, Michael, Neuhold, Erich, and Rannenberg, Kai
Subjects: Information security, business.industry, Internet privacy, Cloud computing, Technological evolution, Service provider, Privacy, SDG 17 - Partnerships for the Goals, Mergers and acquisitions, Data Protection Act 1998, [INFO]Computer Science [cs], Privacy law, business, Working group
Abstract: TC 11: Security and Privacy Protection in Information Processing Systems; International audience; The ongoing demand for new and faster technologies continues to leave consumers and business users to face the constant challenge of updating systems and software. This unrelenting pace of technological evolution has not always been matched with a commensurate focus on security and privacy matters. In particular, the obligatory move to embrace cloud and IoT - that frequently result in the collection and analysis of large data lakes has raised challenges for sovereign data protection and privacy legislation where data at rest can change overnight with mergers and acquisitions of service providers. This chapter examines the role of IFIP Technical Committee 11 (and its 14 underlying Working Groups) in this ever-changing and evolving domain. The discussion provides an outline of key issues in information security when viewed from technical, organisational and human perspectives, which collectively represent the breadth of areas within which TC-11 and its Working Groups are seeking to make contributions. The chapter as a whole gives a clear sense of the challenges involved in achieving and maintaining security and privacy, alongside insights into the ways that they are being tackled within IFIP activities.
Published: 2021

37. Circuit Design Steps for Nano-Crossbar Arrays: Area-Delay-Power Optimization With Fault Tolerance

Author: Valentina Ciriani, Elena Ioana Vatajelu, Dan Alexandrescu, Luca Frontini, Mircea R. Stan, Muhammed Ceylan Morgul, Onur Tunali, Mustafa Altun, Csaba Andras Moritz, Lorena Anghel, Istanbul Technical University (ITÜ), Università degli Studi di Milano = University of Milan (UNIMI), SPINtronique et TEchnologie des Composants (SPINTEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Architectures and Methods for Resilient Systems (TIMA-AMfoRS ), Techniques de l'Informatique et de la Microélectronique pour l'Architecture des systèmes intégrés (TIMA), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), University of Massachusetts [Amherst] (UMass Amherst), University of Massachusetts System (UMASS), University of Virginia, iROc Technologies (IROC TECHNOLOGIES), Cadence Connection-EDA Consortium-FSA-Cubic Micro, Università degli Studi di Milano [Milano] (UNIMI), Architectures and Methods for Resilient Systems (AMfoRS ), and University of Virginia [Charlottesville]
Subjects: Computer science, Circuit design, Fault tolerance, Hardware_PERFORMANCEANDRELIABILITY, 02 engineering and technology, Memristor, 021001 nanoscience & nanotechnology, Fault (power engineering), Computer Science Applications, Power optimization, law.invention, PACS 8542, Logic synthesis, CMOS, law, Electronic engineering, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, Electrical and Electronic Engineering, Crossbar switch, 0210 nano-technology, ComputingMilieux_MISCELLANEOUS, Hardware_LOGICDESIGN
Abstract: Nano-crossbar arrays have emerged to achieve high performance computing beyond the limits of current CMOS with the drawback of higher fault rates. They offer area and power efficiency in terms of their easy-to-fabricate and dense physical structures. They consist of regularly placed crosspoints as computing elements, which behave as diode, memristor, field effect transistor, or novel four-terminal switching devices. In this study, we establish a complete design framework for crossbar circuits explaining and analyzing every step of the process. We comparatively elaborate on these technologies in the sense of their capabilities for computation regarding area including a new logic synthesis technique for memristors, fault tolerance including a novel paradigm for four-terminal devices, delay, and power consumption. As a result, this study introduces a synthesis methodology that considers basic technology preference for switching crosspoints and fault rates of the given crossbar as well as their effects on performance metrics including power, delay, and area.
Published: 2021

38. Minimum Information for Reporting on the Comet Assay (MIRCA)

Author: Andrew Collins, Mirta Milić, Cristian Del Bo, Elisa Boutet-Robinet, Lisa Giovannelli, Amaya Azqueta, Stefano Bonassi, Gunnar Brunborg, Sabine A. S. Langie, Monika Sramkova, Matjaz Novak, Solange Costa, Alena Gábelová, Goran Gajski, Helga Stopper, Roger W. L. Godschalk, Maria Dusinska, Bojana Zegura, Elke Richling, Marcus S. Cooke, Sona Vodenkova, Kristine B. Gutzkow, Vanessa Moraes de Andrade, Cristiana Pereira, Nurşen Başaran, Blanca Laffon, João Paulo Teixeira, Peter Møller, Gudrun Koppen, Pavel Vodicka, Vanessa Valdiglesias, Azqueta, Amaya/0000-0003-4857-9931, Pereira, Cristiana/0000-0002-2146-1223, bonassi, stefano/0000-0003-3833-6717, Boutet-Robinet, Elisa/0000-0002-5223-4568, Paulo Teixeira, Joao/0000-0001-8693-5250, University of Copenhagen = Københavns Universitet (KU), Universidad de Navarra [Pamplona] (UNAV), IdiSNA, Navarra Institute for Health Research, Contaminants & Stress Cellulaire (ToxAlim-COMICS), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Flemish Institute for Technological Research (VITO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS San Raffaele Pisana), Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Institute for Medical Research and Occupational Health, Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), Universidade do Porto, Norwegian Institute for Air Research (NILU), School of Nutrition and Translational Research in Metabolism [Maastricht] (NUTRIM), Maastricht University [Maastricht], Norwegian Institute of Public Health [Oslo] (NIPH), NEUROFARBA Department [Firenze, Italy], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), University of South Florida [Tampa] (USF), Food Chemistry and Toxicology [Kaiserslautern, Germany] (Department of Chemistry), University of Kaiserslautern-University of Kaiserslautern [Germany], Universidade da Coruña, Instituto de Investigación Biomédica de A Coruña [La Corogne, Espagne] (INIBIC), A Coruña University Hospital [La Corogne, Espagne], Hacettepe University = Hacettepe Üniversitesi, Università degli Studi di Milano [Milano] (UNIMI), National Institute of Biology [Ljubljana] (NIB), University of Würzburg, Czech Academy of Sciences [Prague] (CAS), Charles University [Prague] (CU), University of Southern Santa Catarina [Florianopolis] (UNISUL), Slovak Academy of Sciences (SAS), University of Oslo (UiO), Hasselt University (UHasselt), Instituto de Saúde Pública da Universidade do Porto, Farmacologie en Toxicologie, and RS: NUTRIM - R3 - Respiratory & Age-related Health
Subjects: Consensus, Computer science, MIGRATION, [SDV]Life Sciences [q-bio], Recommendations, OXIDATION, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, WHALES, 0302 clinical medicine, INTER-LABORATORY VARIATION, Humans, Experimental work, 030304 developmental biology, Protocol (science), REPAIR, 0303 health sciences, Consensus Statement, food and beverages, BASE, 3. Good health, TIME, Comet assay, Risk analysis (engineering), Risk factors, DNA-DAMAGE, ANIMAL-MODELS, Research Design, 030220 oncology & carcinogenesis, comet assay, variability, information, CELLS, Minimum Information for Reporting Comet Assay (MIRCA), Comet Assay, Guideline Adherence, Laboratories, Biomarkers, DNA Damage
Abstract: The comet assay is a widely used test for the detection of DNA damage and repair activity. However, there are interlaboratory differences in reported levels of baseline and induced damage in the same experimental systems. These differences may be attributed to protocol differences, although it is difficult to identify the relevant conditions because detailed comet assay procedures are not always published. Here, we present a Consensus Statement for the Minimum Information for Reporting Comet Assay (MIRCA) providing recommendations for describing comet assay conditions and results. These recommendations differentiate between ‘desirable’ and ‘essential’ information: ‘essential’ information refers to the precise details that are necessary to assess the quality of the experimental work, whereas ‘desirable’ information relates to technical issues that might be encountered when repeating the experiments. Adherence to MIRCA recommendations should ensure that comet assay results can be easily interpreted and independently verified by other researchers., Here, members of the hCOMET COST Action program provide a consensus statement on the Minimum Information for Reporting Comet Assays (MIRCA).
Published: 2020

39. The Arabidopsis TFIID factor AtTAF6 controls pollen tube growth

Author: Elisabetta Caporali, Martin M. Kater, Lucia Colombo, Ludovico Dreni, Elena Clerici, Christine Horlow, Clara Lago, Università degli Studi di Milano [Milano] (UNIMI), Unité de recherche Génétique et amélioration des plantes (GAP), Institut National de la Recherche Agronomique (INRA), Dipartimento di Biologia, and Università degli Studi di Milano [Milano] (UNIMI)-Sez. Zoologia Scienze Naturali
Subjects: 0106 biological sciences, DNA, Bacterial, DNA, Plant, TATA box, Molecular Sequence Data, POLLEN TUBE, Biology, Genes, Plant, 01 natural sciences, 03 medical and health sciences, Amino Acid Sequence, TRANSCRIPTION, Molecular Biology, [SDV.BDD]Life Sciences [q-bio]/Development Biology, 030304 developmental biology, TAF6, Genetics, 0303 health sciences, General transcription factor, Base Sequence, Sequence Homology, Amino Acid, BRASSICACEAE, Arabidopsis Proteins, TFIID, Gene Expression Regulation, Developmental, Cell Biology, BIOLOGIE MOLECULAIRE, ARABIDOPSIS, GAMETOPHYTE, TAF1, Mutagenesis, Insertional, TAF4, Transcription Factor TFIID, TAF2, Pollen, Genes, Lethal, Transcription factor II B, Transcription factor II A, 010606 plant biology & botany, Developmental Biology
Abstract: International audience; Initiation of transcription mediated by RNA polymerase II requires a number of transcription factors among which TFIID is the major core promoter recognition factor. TFIID is composed of highly conserved factors which include the TATA-binding protein (TBP) and about 14 TBP-associated factors (TAFs). Recently, the complete Arabidopsis TAF family has been identified. To obtain functional information about Arabidopsis TAFs, we analyzed a T-DNA insertion mutant for AtTAF6. Segregation analysis showed that plants homozygous for the mutant allele were never found, indicating that inhibition of the AtTAF6 function is lethal. Genetic experiments also revealed that the male gametophyte was affected by the attaf6 mutation since significant reduced transmission of the mutant allele through the male gametophyte was observed. Detailed histological and morphological analysis showed that the T-DNA insertion in AtTAF6 specifically affects pollen tube growth, indicating that the transcriptional regulation of only a specific subset of genes is controlled by this basal transcription factor.
Published: 2005

40. EU-OSTID: A collection of transposon insertional mutants for functional genomics in rice

Author: Pieter B. F. Ouwerkerk, Paul Christou, Marta Rafel, L.J.G. van Enckevort, Gaëtan Droc, Andy Pereira, Stefano Berri, Emmanuel Guiderdoni, Pere Cabot, Pietro Piffanelli, Annemarie H. Meijer, Raffaella Greco, Víctor M. González, Lucia Colombo, Teresa Capell, Enrico Pè, Berta Miro, Fabio Fornara, Pere Puigdomènech, Ping Lan, Cyril Gagneur, Christele Weber, European Commission, Plant Research International (PRI), Wageningen University and Research [Wageningen] (WUR), Polymorphismes d'intérêt agronomique (UMR PIA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Dipartimento di Biologia, Università degli Studi di Milano [Milano] (UNIMI)-Sez. Zoologia Scienze Naturali, Università degli Studi di Milano [Milano] (UNIMI), Fraunhofer (Fraunhofer-Gesellschaft), Leiden University, and Publica
Subjects: 0106 biological sciences, family, transposon, ADN, Plant Science, 01 natural sciences, Genome, Homology (biology), F30 - Génétique et amélioration des plantes, TRANSPOSONS, generation, Databases, Genetic, Expression des gènes, REVERSE GENETICS, 2. Zero hunger, Genetics, 0303 health sciences, Chromosome Mapping, Transposition de gènes, food and beverages, General Medicine, Genomics, 3. Good health, PRI Bioscience, annotation, Laboratory of Genetics, Functional genomics, Genome, Plant, mutagenesis, Transposable element, DNA, Bacterial, DNA, Plant, FLANKING SEQUENCE TAG, Oryza sativa, Biology, system, CARTOGRAPHIE GENETIQUE, Laboratorium voor Erfelijkheidsleer, Chromosomes, Plant, activator, 03 medical and health sciences, reverse genetics, Complementary DNA, expression, FUNCTIONAL GENOMICS, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, RICE, Gene, 030304 developmental biology, Whole genome sequencing, Génie génétique, Binding Sites, STRUCTURE DU GENOME, Mutant, Oryza, homeobox genes, Mutagenesis, Insertional, MUTANTS, Gène, Collection de matériel génétique, Mutation, DNA Transposable Elements, resources, Agronomy and Crop Science, RIZ, 010606 plant biology & botany, Transcription Factors
Abstract: A collection of 1373 unique flanking sequence tags (FSTs), generated from Ac/Ds and Ac transposon lines for reverse genetics studies, were produced in japonica and indica rice, respectively. The Ds and Ac FSTs together with the original T-DNAs were assigned a position in the rice genome sequence represented as assembled pseudomolecules, and found to be distributed evenly over the entire rice genome with a distinct bias for predicted gene-rich regions. The bias of the Ds and Ac transposon inserts for genes was exemplified by the presence of 59% of the inserts in genes annotated on the rice chromosomes and 41% present in genes transcribed as disclosed by their homology to cDNA clones. In a screen for inserts in a set of 75 well annotated transcription factors, including homeobox-containing genes, we found six Ac/Ds inserts. This high frequency of Ds and Ac inserts in genes suggests that saturated knockout mutagenesis in rice using this strategy will be efficient and possible with a lower number of inserts than expected. These FSTs and the corresponding plant lines are publicly available through OrygenesDB database and from the EU consortium members., We acknowledge the support of the EU 5th framework project QLG2-CT-2001-01453 CerealGene Tags.
Published: 2005
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41. BETs inhibition attenuates oxidative stress and preserves muscle integrity in Duchenne muscular dystrophy

Author: L. Nevi, Panagis Filippakopoulos, Raffaella Fittipaldi, Marco Segatto, Roberta Szokoll, Kamel Mamchaoui, Cinzia Bottino, Giuseppina Caretti, Università degli Studi di Milano [Milano] (UNIMI), University of Molise [Campobasso] (UNIMOL), University of Molise, Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Myologie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford [Oxford], Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Centre de recherche en Myologie – U974 SU-INSERM, Università degli Studi di Milano = University of Milan (UNIMI), Università degli Studi del Molise = University of Molise (UNIMOL), University of Oxford, and Gestionnaire, Hal Sorbonne Université
Subjects: 0301 basic medicine, mdx mouse, Duchenne muscular dystrophy, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Skeletal muscle, medicine.disease_cause, Inbred C57BL, Mice, 0302 clinical medicine, Myocyte, Muscular Dystrophy, Multidisciplinary, NADPH oxidase, biology, Nuclear Proteins, Azepines, Skeletal, Neuromuscular Diseases, Neuromuscular disease, 3. Good health, Cell biology, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Muscle, Epigenetics, medicine.symptom, Animals, Disease Models, Animal, Inflammation, Mice, Inbred C57BL, Mice, Inbred mdx, Muscle, Skeletal, Muscular Dystrophy, Duchenne, NADP, NADPH Oxidases, Oxidative Stress, Reactive Oxygen Species, Transcription Factors, Triazoles, musculoskeletal diseases, congenital, hereditary, and neonatal diseases and abnormalities, Science, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, medicine, business.industry, Animal, Inbred mdx, General Chemistry, medicine.disease, Duchenne, Bromodomain, 030104 developmental biology, Disease Models, biology.protein, business, 030217 neurology & neurosurgery, Oxidative stress
Abstract: Duchenne muscular dystrophy (DMD) affects 1 in 3500 live male births. To date, there is no effective cure for DMD, and the identification of novel molecular targets involved in disease progression is important to design more effective treatments and therapies to alleviate DMD symptoms. Here, we show that protein levels of the Bromodomain and extra-terminal domain (BET) protein BRD4 are significantly increased in the muscle of the mouse model of DMD, the mdx mouse, and that pharmacological inhibition of the BET proteins has a beneficial outcome, tempering oxidative stress and muscle damage. Alterations in reactive oxygen species (ROS) metabolism are an early event in DMD onset and they are tightly linked to inflammation, fibrosis, and necrosis in skeletal muscle. By restoring ROS metabolism, BET inhibition ameliorates these hallmarks of the dystrophic muscle, translating to a beneficial effect on muscle function. BRD4 direct association to chromatin regulatory regions of the NADPH oxidase subunits increases in the mdx muscle and JQ1 administration reduces BRD4 and BRD2 recruitment at these regions. JQ1 treatment reduces NADPH subunit transcript levels in mdx muscles, isolated myofibers and DMD immortalized myoblasts. Our data highlight novel functions of the BET proteins in dystrophic skeletal muscle and suggest that BET inhibitors may ameliorate the pathophysiology of DMD., Duchenne muscular dystrophy (DMD) is characterised by progressive muscle degeneration. Here, the authors show that the BET protein BRD4 is increased in the muscle of DMD mouse models, and that pharmacological inhibition of BRD4 leads to reduced muscle pathology in mice, by modulating NADPH oxidase expression.
Published: 2020

42. OsFD4 promotes the rice floral transition via florigen activation complex formation in the shoot apical meristem

Author: Martina Cerise, Andrea Gallavotti, François Parcy, Fabio Fornara, Vittoria Brambilla, Mary Galli, Jérémy Lucas, Francesca Giaume, Elahe Tavakol, Federico Podico, Bahman Khahani, Max Planck Institute for Plant Breeding Research (MPIPZ), Università degli Studi di Milano [Milano] (UNIMI), Rutgers, The State University of New Jersey [New Brunswick] (RU), Rutgers University System (Rutgers), Shiraz University (Shiraz University ), Régulateurs du développement de la fleur (Flo_RE ), Physiologie cellulaire et végétale (LPCV), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), PRIN (no. 20153NM8RM), European Project: 260963,EC:FP7:ERC,ERC-2010-StG_20091118,FLARE(2011), and Università degli Studi di Milano = University of Milan (UNIMI)
Subjects: 0106 biological sciences, 0301 basic medicine, Physiology, In silico, Meristem, Mutant, Repressor, Flowers, Plant Science, Biology, 01 natural sciences, 03 medical and health sciences, chemistry.chemical_compound, Gene Expression Regulation, Plant, bZIP, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene, Transcription factor, Florigen, Plant Proteins, shoot apical meristem, 2. Zero hunger, rice, fungi, food and beverages, Oryza, photoperiodic flowering, [SDV.BV.BOT]Life Sciences [q-bio]/Vegetal Biology/Botanics, Cell biology, florigen activation complex, 030104 developmental biology, chemistry, DNA, 010606 plant biology & botany
Abstract: International audience; In rice, the florigens Heading Date 3a (Hd3a) and Rice Flowering Locus T 1 (RFT1), OsFD-like basic leucine zipper (bZIP) transcription factors, and Gf14 proteins assemble into florigen activation/repressor complexes (FACs/FRCs), which regulate transition to flowering in leaves and apical meristem. Only OsFD1 has been described as part of complexes promoting flowering at the meristem, and little is known about the role of other bZIP transcription factors, the combinatorial complexity of FAC formation, and their DNA-binding properties. Here, we used mutant analysis, protein-protein interaction assays and DNA affinity purification (DAP) sequencing coupled to in silico prediction of binding syntaxes to study several bZIP proteins that assemble into FACs or FRCs. We identified OsFD4 as a component of a FAC promoting flowering at the shoot apical meristem, downstream of OsFD1. The osfd4 mutants are late flowering and delay expression of genes promoting inflorescence development. Protein-protein interactions indicate an extensive network of contacts between several bZIPs and Gf14 proteins. Finally, we identified genomic regions bound by bZIPs with promotive and repressive effects on flowering. We conclude that distinct bZIPs orchestrate floral induction at the meristem and that FAC formation is largely combinatorial. While binding to the same consensus motif, their DNA-binding syntax is different, suggesting discriminatory functions.
Published: 2020

43. Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients

Author: Zuzanna Makowska, Ricard Cervera, Lorenzo Beretta, László Kovács, Marta E. Alarcón-Riquelme, Guillermo Barturen, Isabel Almeida, Divi Cornec, Javier Martín, Jacques-Olivier Pers, Ellen De Langhe, Nicolas Hunzelmann, Carlo Chizzolini, Maria Gerosa, Martin Kerick, Ralf Lesche, Chiara Bellocchi, Barbara Vigone, Rafaela Ortega Castro, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Centre for Genomics and Oncological Research Pfizer [Granada, Spain], Universidad de Granada = University of Granada (UGR)-Andalusian Regional Government [Granada, Spain], Università degli Studi di Milano = University of Milan (UNIMI), Universitätsklinikum Köln (Uniklinik Köln), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University Hospitals Leuven [Leuven], Department of Clinical Sciences and Community Health [Milan, Italy], Hospital Clinic, IDIBAPS, Universidad de Barcelona, Ciberes, Barcelona, Spain., Instituto Maimonides de Investigación Biomédica de Cordoba (IMIBIC), Universidad de Córdoba = University of Córdoba [Córdoba]-Hospital Universitario Reina Sofía, University of Szeged [Szeged], CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Hôpital Universitaire de Genève, Geneva, Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Bayer Pharma AG [Berlin], Instituto de Parasitología y Biomedicina 'López-Neyra', PRECISESADS SSc substudy group, PRECISESADS Flow Cytometry study group : Doreen Belz, Eduardo Collantes-Estevez, Francesca Ingegnoli, Yolanda Jimenez Gómez, Chary Lopez Pedrera, Rik Lories, Gaia Montanelli, Silvia Piantoni, Ignasi Rodriguez Pinto, Carlos Vasconcelos, Christophe Jamin, Concepción Marañón, Lucas Le Lann, Quentin Simon, Bénédicte Rouvière, Nieves Varela, Brian Muchmore, Aleksandra Dufour, Montserrat Alvarez, Jonathan Cremer, Nuria Barbarroja, Velia Gerl, Laleh Khodadadi, Qingyu Cheng, Anne Buttgereit, Aurélie De Groof, Julie Ducreux, Elena Trombetta, Tianlu Li, Damiana Alvarez-Errico, Torsten Witte, Katja Kniesch, Nancy Azevedo, Esmeralda Neves, Sambasiva Rao, Pierre-Emmanuel Jouve., Michel, Geneviève, University of Granada [Granada]-Andalusian Regional Government [Granada, Spain], University of Milan, University Hospitals Leuven and Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium, Università degli Studi di Milano [Milano] (UNIMI), Universidad de Córdoba [Cordoba]-Hospital Universitario Reina Sofía, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Universitaire de Genève, and European Commission
Subjects: MESH: Interferon Type I, MESH: Signal Transduction, Male, 0301 basic medicine, Microarray, systemic sclerosis, Autoimmunity, Diseases, Pathogenesis, DISEASE, MESH: Scleroderma, Systemic, Cohort Studies, Transcriptome, 0302 clinical medicine, Immunophenotyping, Platelet degranulation, Gene expression, MESH: Sequence Analysis, RNA, Immunology and Allergy, Medicine, RNA-Seq, MESH: Cohort Studies, GENE-EXPRESSION, MESH: Aged, MESH: Middle Aged, Toll-Like Receptors, Middle Aged, 3. Good health, Europe, Interferon Type I, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, epidemiology, Life Sciences & Biomedicine, MESH: Toll-Like Receptors, Signal Transduction, Adult, MESH: Immunophenotyping, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Context (language use), Systemic Sclerosis, Computational biology, General Biochemistry, Genetics and Molecular Biology, MESH: Gene Expression Profiling, 03 medical and health sciences, Rheumatology, MESH: Autoimmunity, Humans, autoimmune diseases, Gene, Aged, 030203 arthritis & rheumatology, Science & Technology, MESH: Humans, Scleroderma, Systemic, Sequence Analysis, RNA, business.industry, MESH: Transcriptome, Gene Expression Profiling, RNA, MESH: Adult, Microarray Analysis, Expressió gènica, MESH: Male, MESH: Microarray Analysis, Scleroderma (Disease), 030104 developmental biology, MESH: Genome-Wide Association Study, MESH: Europe, Esclerodèrmia, business, MESH: Female, Genome-Wide Association Study
Abstract: Objectives: The analysis of annotated transcripts from genome-wide expression studies may help to understand the pathogenesis of complex diseases, such as systemic sclerosis (SSc). We performed a whole blood (WB) transcriptome analysis on RNA collected in the context of the European PRECISESADS project, aiming at characterising the pathways that differentiate SSc from controls and that are reproducible in geographically diverse populations. Methods: Samples from 162 patients and 252 controls were collected in RNA stabilisers. Cases and controls were divided into a discovery (n=79+163; Southern Europe) and validation cohort (n=83+89; Central-Western Europe). RNA sequencing was performed by an Illumina assay. Functional annotations of Reactome pathways were performed with the Functional Analysis of Individual Microarray Expression (FAIME) algorithm. In parallel, immunophenotyping of 28 circulating cell populations was performed. We tested the presence of differentially expressed genes/pathways and the correlation between absolute cell counts and RNA transcripts/FAIME scores in regression models. Results significant in both populations were considered as replicated. Results: Overall, 15 224 genes and 1277 functional pathways were available; of these, 99 and 225 were significant in both sets. Among replicated pathways, we found a deregulation in type-I interferon, Toll-like receptor cascade, tumour suppressor p53 protein function, platelet degranulation and activation. RNA transcripts or FAIME scores were jointly correlated with cell subtypes with strong geographical differences; neutrophils were the major determinant of gene expression in SSc-WB samples. Conclusions: We discovered a set of differentially expressed genes/pathways validated in two independent sets of patients with SSc, highlighting a number of deregulated processes that have relevance for the pathogenesis of autoimmunity and SSc., This work was supported by eU/eFPia/innovative Medicines initiative Joint Undertaking PrecisesaDs Grant no. 115 565.
Published: 2020

44. Non-integrable Dimers: Universal Fluctuations of Tilted Height Profiles

Author: Fabio Lucio Toninelli, Vieri Mastropietro, Alessandro Giuliani, Department of Mathematics and Physics, Università degli Studi Roma Tre, Università degli Studi di Milano [Milano] (UNIMI), Institut Camille Jordan [Villeurbanne] (ICJ), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Probabilités, statistique, physique mathématique (PSPM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Vienna University of Technology (TU Wien), ANR-10-LABX-0070,MILYON,Community of mathematics and fundamental computer science in Lyon(2010), ANR-15-CE40-0020,LSD,Modèles stochastiques en grande dimension pour la physique statistique hors équilibre(2015), ANR-18-CE40-0033,DIMERS,Dimères : de la combinatoire à la mécanique quantique(2018), Giuliani, Alessandro, Mastropietro, Vieri, and Toninelli, Fabio Lucio
Subjects: Physics, Physical constant, Probability (math.PR), 010102 general mathematics, FOS: Physical sciences, Statistical and Nonlinear Physics, Mathematical Physics (math-ph), Renormalization group, Lambda, 01 natural sciences, Square lattice, [MATH.MATH-PR]Mathematics [math]/Probability [math.PR], Massless particle, Amplitude, 0103 physical sciences, FOS: Mathematics, Exponent, Condensed Matter::Strongly Correlated Electrons, 0101 mathematics, 010306 general physics, Scaling, Mathematics - Probability, Mathematical Physics, Mathematical physics
Abstract: We study a class of close-packed dimer models on the square lattice, in the presence of small but extensive perturbations that make them non-determinantal. Examples include the 6-vertex model close to the free-fermion point, and the dimer model with plaquette interaction previously analyzed in \cite{A,AL,GMT17a,GMT17b}. By tuning the edge weights, we can impose a non-zero average tilt for the height function, so that the considered models are in general not symmetric under discrete rotations and reflections. In the determinantal case, height fluctuations in the massless (or `liquid') phase scale to a Gaussian log-correlated field and their amplitude is a universal constant, independent of the tilt. When the perturbation strength $\lambda$ is sufficiently small we prove, by fermionic constructive Renormalization Group methods, that log-correlations survive, with amplitude $A$ that, generically, depends non-trivially and non-universally on $\lambda$ and on the tilt. On the other hand, $A$ satisfies a universal scaling relation (`Haldane' or `Kadanoff' relation), saying that it equals the anomalous exponent of the dimer-dimer correlation., Comment: 78 pages, 5 figures. Version accepted for publication on Comm. Math. Phys. Compared to previous version, a few more details have been added in Sect.6.5 on the finite size corrections to the correlation functions, see in particular eqs.(6.132), (6.133) and following discussion
Published: 2020

45. Shedding X-ray Light on the Role of Magnesium in the Activity of Mycobacterium tuberculosis Salicylate Synthase (MbtI) for Drug Design

Author: Arianna Gelain, Fiorella Meneghetti, Josè Camilla Sammartino, Giulio Poli, Elena Pini, Stefania Villa, Laurent R. Chiarelli, Marco Bellinzoni, Giovanni Stelitano, Alessio Porta, Giangiacomo Beretta, Tiziano Tuccinardi, M. Mori, Università degli Studi di Milano [Milano] (UNIMI), Università degli Studi di Pavia, University of Pisa - Università di Pisa, Temple University [Philadelphia], Pennsylvania Commonwealth System of Higher Education (PCSHE), Microbiologie structurale - Structural Microbiology (Microb. Struc. (UMR_3528 / U-Pasteur_5)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), This work was funded by University of Milan (Linea B) and the Italian Ministry of Education, University and Research (MIUR): Dipartimenti di Eccellenza Program (2018–2022) - Dept. of Biology and Biotechnology 'L. Spallanzani', University of Pavia. Partial support was also provided by institutional grants from Institut Pasteur and CNRS., Università degli Studi di Milano = University of Milan (UNIMI), Università degli Studi di Pavia = University of Pavia (UNIPV), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: Models, Molecular, Siderophore, MESH: Mycobacterium tuberculosis, Protein Conformation, MESH: Drug Design, Crystallography, X-Ray, 01 natural sciences, MESH: Protein Conformation, MESH: Structure-Activity Relationship, Models, MESH: Magnesium, Drug Discovery, Magnesium, Ternary complex, chemistry.chemical_classification, 0303 health sciences, Crystallography, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], biology, ATP synthase, 3. Good health, Biochemistry, Molecular Medicine, MESH: Models, Molecular, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Lyases, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Cofactor, Article, Mycobacterium tuberculosis, 03 medical and health sciences, Structure-Activity Relationship, [CHIM.CRIS]Chemical Sciences/Cristallography, Structure–activity relationship, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Rational design, Molecular, MESH: Crystallography, X-Ray, biology.organism_classification, MESH: Lyases, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, Enzyme, chemistry, Drug Design, X-Ray, biology.protein, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM]
Abstract: International audience; The Mg2+-dependent Mycobacterium tuberculosis salicylate synthase (MbtI) is a key enzyme involved in the biosynthesis of siderophores. Because iron is essential for the survival and pathogenicity of the microorganism, this protein constitutes an attractive target for antitubercular therapy, also considering the absence of homologous enzymes in mammals. An extension of the structure-activity relationships of our furan-based candidates allowed us to disclose the most potent competitive inhibitor known to date (10, Ki = 4 μM), which also proved effective on mycobacterial cultures. By structural studies, we characterized its unexpected Mg2+-independent binding mode. We also investigated the role of the Mg2+ cofactor in catalysis, analyzing the first crystal structure of the MbtI-Mg2+-salicylate ternary complex. Overall, these results pave the way for the development of novel antituberculars through the rational design of improved MbtI inhibitors.
Published: 2020

46. Persistence of environmental DNA in cultivated soils: implication of this memory effect for reconstructing the dynamics of land use and cover changes

Author: J. Patrick Laceby, Ludovic Gielly, Julie Poulain, Olivier Evrard, G. Francesco Ficetola, Charline Giguet-Covex, Olivier Cerdan, Anthony Foucher, Jérôme Poulenard, Sébastien Salvador-Blanes, Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Géochimie Des Impacts (GEDI), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Università degli Studi di Milano [Milano] (UNIMI), Laboratoire d'Ecologie Alpine (LECA ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Environnements, Dynamiques et Territoires de la Montagne (EDYTEM), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Alberta Environment and Parks (AEP), GéoHydrosystèmes COntinentaux (GéHCO EA6293), Université de Tours, Bureau de Recherches Géologiques et Minières (BRGM) (BRGM), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Université de Tours (UT), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano = University of Milan (UNIMI), and Environnements, Dynamiques et Territoires de Montagne (EDYTEM)
Subjects: 0106 biological sciences, 0301 basic medicine, Agricultural genetics, Geologic Sediments, Plant genetics, DNA, Plant, Ecosystem ecology, [SDE.MCG]Environmental Sciences/Global Changes, Biodiversity, lcsh:Medicine, Land cover, [SDV.SA.SDS]Life Sciences [q-bio]/Agricultural sciences/Soil study, 010603 evolutionary biology, 01 natural sciences, Article, Crop, 03 medical and health sciences, Soil, Abundance (ecology), [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Environmental DNA, [SDU.STU.GM]Sciences of the Universe [physics]/Earth Sciences/Geomorphology, [SDU.ENVI]Sciences of the Universe [physics]/Continental interfaces, environment, lcsh:Science, 2. Zero hunger, Multidisciplinary, Land use, Ecology, lcsh:R, 15. Life on land, Crop rotation, Plants, DNA, Environmental, Lakes, 030104 developmental biology, Geography, Soil water, [SDE]Environmental Sciences, lcsh:Q, France
Abstract: eDNA refers to DNA extracted from an environmental sample with the goal of identifying the occurrence of past or current biological communities in aquatic and terrestrial environments. However, there is currently a lack of knowledge regarding the soil memory effect and its potential impact on lake sediment eDNA records. To investigate this issue, two contrasted sites located in cultivated environments in France were studied. In the first site, soil samples were collected (n = 30) in plots for which the crop rotation history was documented since 1975. In the second site, samples were collected (n = 40) to compare the abundance of currently observed taxa versus detected taxa in cropland and other land uses. The results showed that the last cultivated crop was detected in 100% of the samples as the most abundant. In addition, weeds were the most abundant taxa identified in both sites. Overall, these results illustrate the potential of eDNA analyses for identifying the recent (
Published: 2020

47. Transitioning the total hip arthroplasty technique from posterior approach in lateral position to direct anterior approach in supine position—risk factors for acetabular malpositioning and the learning curve

Author: Francesco Luceri, Cécile Batailler, Cam Fary, Constant Foissey, Elvire Servien, Sébastien Lustig, Service de Chirurgie Orthopédique [Centre Albert Trillat], Centre Albert Trillat [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), University of Melbourne, Università degli Studi di Milano [Milano] (UNIMI), Laboratoire de Biomécanique et Mécanique des Chocs (LBMC UMR T9406 ), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Gustave Eiffel
Subjects: medicine.medical_specialty, Supine position, CUP POSITIONING, Arthroplasty, Replacement, Hip, Radiography, Antiviral Agents, Posterior approach, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Bearing surface, Supine Position, medicine, Humans, INSTRUMENTATION, Orthopedics and Sports Medicine, Retrospective Studies, 030203 arthritis & rheumatology, Orthodontics, 030222 orthopedics, business.industry, TOTAL HIP ARTHROPLASTY, [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], Acetabulum, Hepatitis C, Chronic, DIRECT ANTERIOR APPROACH, Learning curve, Orthopedic surgery, Female, Surgery, Hip Prosthesis, Anterior approach, business, Learning Curve, Total hip arthroplasty
Abstract: PURPOSE: Cup positioning is important for optimum hip stability, avoiding component impingement and decreasing both bearing surface wear and revision rate. Transitioning from posterior approach in a lateral position to direct anterior approach (DAA) in a supine presents unique challenges for surgeons. The aim of this study was to examine the learning curve when using standard instrumentation that was not specific to DAA. METHODS: A consecutive retrospective series of 537 total hip arthroplasty by DAA from May 2013 to December 2017. Cup positioning was analysed on radiographs and classified whether inside or outside two safe zones (inclination 30-50° and anteversion 10-30°). The demographic data (age, BMI, gender, neck shaft angle (NSA)), surgeon's dominant side and experience were assessed as risk factors. RESULTS: Eighty per cent of cups (n=426) were in the combined safe zones. Eighty-eight per cent (n=470) were in appropriate anteversion and 87% (n=463) abduction. Two factors that were significant were identified: Cups of left hips operated by right-handed surgeons were more anteverted (OR=4.06) and more vertical (OR=2.23); females had a higher anteversion of the cup (OR=2.42). Obesity, age and NSA were not risk factors for cup malposition. There was a spike of cups too horizontal at the beginning of the experience (OR=3.86), and no learning curve was observed in the other orientations. CONCLUSION: With our DAA technique using standard instrumentation, there were no risk factors linked to the patient identified for cup malposition. DAA-specific instrumentation is not required to achieve optimum positioning of the cup. Surgeon has to be aware of an excess of abduction at the beginning of his experience and an excess of anteversion and adduction when performing THA on the opposite side of his dominant hand.
Published: 2020

48. The COVID-19 pandemic: is there a role for magnesium? Hypotheses and perspectives

Author: Stefano Iotti, Federica I Wolf, Jeanette A.M. Maier, André Mazur, University of Bologna, Università cattolica del Sacro Cuore [Roma] (Unicatt), Unité de Nutrition Humaine (UNH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Università degli Studi di Milano [Milano] (UNIMI), Iotti S., Wolf F., Mazur A., Maier J.A., University of Bologna/Università di Bologna, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), and Università degli Studi di Milano = University of Milan (UNIMI)
Subjects: 0301 basic medicine, Time Factors, T-Lymphocytes, Clinical Biochemistry, Disease, magnesium, 030204 cardiovascular system & hematology, Biochemistry, Pathogenesis, 0302 clinical medicine, Epidemiology, Pandemic, Medicine, Endothelial dysfunction, Inflammation Mediator, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Prognosis, 3. Good health, Host-Pathogen Interaction, Host-Pathogen Interactions, Disease Progression, Inflammation Mediators, medicine.symptom, Coronavirus Infections, Human, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Prognosi, Pneumonia, Viral, Inflammation, Proinflammatory cytokine, Betacoronavirus, 03 medical and health sciences, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Pandemics, Molecular Biology, Betacoronaviru, Animal, Coronavirus Infection, SARS-CoV-2, business.industry, pandemic, COVID-19, medicine.disease, 030104 developmental biology, T-Lymphocyte, inflammation, Immunology, business, Magnesium Deficiency
Abstract: International audience; More and more studies are accumulating about COVID-19. Some aspects of the pathogenesis of the disease recall events occurring in Mg deficiency, such as a drop of T cells, increased plasma concentration of inflammatory cytokines, and endothelial dysfunction. We hypothesize that a low Mg status, which is rather common, might foment the transition from mild to critical clinical manifestations of the disease. Epidemiological, clinical, and fundamental research is needed to clarify the potential role of Mg deficiency in COVID-19.
Published: 2020

49. Optimal switching problems with an infinite set of modes: An approach by randomization and constrained backward SDEs

Author: Marie Amelie Morlais, Marco Fuhrman, Dipartimento di Matematica, Università degli Studi di Milano [Milano] (UNIMI), Laboratoire Manceau de Mathématiques (LMM), and Le Mans Université (UM)
Subjects: Statistics and Probability, Infinite set, Optimization problem, backward SDEs, Differential equation, MathematicsofComputing_NUMERICALANALYSIS, randomization of controls, 01 natural sciences, 010104 statistics & probability, Stochastic differential equation, Bellman equation, FOS: Mathematics, AMS 2010: 60H10, 93E20, Applied mathematics, 0101 mathematics, Mathematics - Optimization and Control, Brownian motion, Mathematics, Applied Mathematics, Probability (math.PR), 010102 general mathematics, Probabilistic logic, [MATH.MATH-PR]Mathematics [math]/Probability [math.PR], Optimization and Control (math.OC), stochastic optimal switching, Modeling and Simulation, [MATH.MATH-OC]Mathematics [math]/Optimization and Control [math.OC], Martingale (probability theory), Mathematics - Probability, 60H10, 93E20
Abstract: We address a general optimal switching problem over finite horizon for a stochastic system described by a differential equation driven by Brownian motion. The main novelty is the fact that we allow for infinitely many modes (or regimes, i.e. the possible values of the piecewise-constant control process). We allow all the given coefficients in the model to be path-dependent, that is, their value at any time depends on the past trajectory of the controlled system. The main aim is to introduce a suitable (scalar) backward stochastic differential equation (BSDE), with a constraint on the martingale part, that allows to give a probabilistic representation of the value function of the given problem. This is achieved by randomization of control, i.e. by introducing an auxiliary optimization problem which has the same value as the starting optimal switching problem and for which the desired BSDE representation is obtained. In comparison with the existing literature we do not rely on a system of reflected BSDE nor can we use the associated Hamilton-Jacobi-Bellman equation in our non-Markovian framework., Comment: 36 pages
Published: 2020

50. Functionalized Iron Hydroxyapatite as Eco‐friendly Catalyst for NH 3 ‐SCR Reaction: Activity and Role of Iron Speciation on the Surface

Author: Sergio Gustavo Marchetti, Aline Auroux, Georgeta Postole, M.G. Galloni, Sebastiano Campisi, Antonella Gervasini, Dipartimento di Chimica, Università degli Studi di Milano [Milano] (UNIMI), Centro de Investigación y Desarrollo en Ciencias Aplicadas [Buenos Aires] (CINDECA), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Universidad Nacional de la Plata [Argentine] (UNLP), IRCELYON-Approches thermodynamiques, analytiques et réactionnelles intégrées (ATARI), Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Iron hydroxyapatite, 010405 organic chemistry, Organic Chemistry, Ionic bonding, [CHIM.CATA]Chemical Sciences/Catalysis, 010402 general chemistry, 01 natural sciences, Catalysis, 0104 chemical sciences, Nanoclusters, Catalyst preparation, Inorganic Chemistry, Ammonia, chemistry.chemical_compound, Adsorption, chemistry, Moessbauer spectroscopy, Environmental chemistry, Mössbauer spectroscopy, Denitrification, Physical and Theoretical Chemistry, Selectivity, NOx, Nuclear chemistry
Abstract: SSCI-VIDE+ATARI:CARE+MGL:AAU:GPO; International audience; Eco‐friendly catalysts have been obtained by functionalizing hydroxyapatite (HAP) with iron (Fe/HAP), according to three preparative methods (flash ionic exchange, deposition‐precipitation, and impregnation). Fe/HAP samples (ca . 2–7 wt.% Fe) have been tested in the reaction of NOx reduction by ammonia (NH3‐SCR) in the 120–500 °C interval with different NH3/NO ratios (0.6–2) at fixed contact time (0.12 s). All Fe/HAP samples were active and selective in the NH3‐SCR reaction starting from ca . 350 °C. Better performances have been observed on catalysts prepared by deposition‐precipitation and impregnation (about 70 % of NOx conversion and selectivity to N2 higher than 95 % at 350 °C), where α‐Fe2O3 and 3D ‐Fe2O3 nanoclusters were present, as indicated by Mössbauer and UV‐Vis‐DR spectroscopies. On the opposite, paramagnetic Fe3+ centres were the predominant species on samples prepared by flash ionic exchange. Further characterization techniques (XRPD, N2‐physisorption, acidity by NH3 adsorption, and H2‐TPR) have concurred to elucidate Fe‐sitting HAP and structure‐activity relationships.
Published: 2020

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