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26,421 results on '"Coste A"'

153. CNS neuroblastoma, FOXR2-activated and its mimics: a relevant panel approach for work-up and accurate diagnosis of this rare neoplasm

Author

Tauziède-Espariat, Arnault, Figarella-Branger, Dominique, Métais, Alice, Uro-Coste, Emmanuelle, Maurage, Claude-Alain, Lhermitte, Benoît, Aline-Fardin, Aude, Hasty, Lauren, Vasiljevic, Alexandre, Chiforeanu, Dan, Chotard, Guillaume, Adle-Biassette, Homa, Meurgey, Alexandra, Saffroy, Raphaël, Guillemot, Delphine, Pierron, Gaëlle, Sievers, Philipp, and Varlet, Pascale

Published
2023
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154. CNS tumor with EP300::BCOR fusion: discussing its prevalence in adult population

Author

Tauziède-Espariat, Arnault, Uro-Coste, Emmanuelle, Sievers, Philipp, Nicaise, Yvan, Mariet, Cassandra, Siegfried, Aurore, Pierron, Gaëlle, Guillemot, Delphine, Benzakoun, Joseph, Pallud, Johan, Roques, Margaux, Bonneville, Fabrice, Larrieu-Ciron, Delphine, Chaynes, Patrick, Saffroy, Raphaël, Hamelin, Jocelyne, Hasty, Lauren, Métais, Alice, Chrétien, Fabrice, Kool, Marcel, Gojo, Johannes, and Varlet, Pascale

Published
2023
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157. Hyperglycemia triggers RyR2-dependent alterations of mitochondrial calcium homeostasis in response to cardiac ischemia-reperfusion: Key role of DRP1 activation

Author

Mathilde Dubois, Doria Boulghobra, Gilles Rochebloine, Florian Pallot, Marc Yehya, Isabelle Bornard, Sandrine Gayrard, Florence Coste, Guillaume Walther, Gregory Meyer, Jean-Charles Gaillard, Jean Armengaud, Béatrice Alpha-Bazin, and Cyril Reboul

Subjects
Mitochondria, Calcium homeostasis, Hyperglycemia, Ischemia-reperfusion, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Hyperglycemia increases the heart sensitivity to ischemia-reperfusion (IR), but the underlying cellular mechanisms remain unclear. Mitochondrial dynamics (the processes that govern mitochondrial morphology and their interactions with other organelles, such as the reticulum), has emerged as a key factor in the heart vulnerability to IR. However, it is unknown whether mitochondrial dynamics contributes to hyperglycemia deleterious effect during IR. We hypothesized that (i) the higher heart vulnerability to IR in hyperglycemic conditions could be explained by hyperglycemia effect on the complex interplay between mitochondrial dynamics, Ca2+ homeostasis, and reactive oxygen species (ROS) production; and (ii) the activation of DRP1, a key regulator of mitochondrial dynamics, could play a central role. Using transmission electron microscopy and proteomic analysis, we showed that the interactions between sarcoplasmic reticulum and mitochondria and mitochondrial fission were increased during IR in isolated rat hearts perfused with a hyperglycemic buffer compared with hearts perfused with a normoglycemic buffer. In isolated mitochondria and cardiomyocytes, hyperglycemia increased mitochondrial ROS production and Ca2+ uptake. This was associated with higher RyR2 instability. These results could contribute to explain the early mPTP activation in mitochondria from isolated hearts perfused with a hyperglycemic buffer and in hearts from streptozotocin-treated rats (to increase the blood glucose). DRP1 inhibition by Mdivi-1 during the hyperglycemic phase and before IR induction, normalized Ca2+ homeostasis, ROS production, mPTP activation, and reduced the heart sensitivity to IR in streptozotocin-treated rats. In conclusion, hyperglycemia-dependent DRP1 activation results in higher reticulum-mitochondria calcium exchange that contribute to the higher heart vulnerability to IR.

Published
2024
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158. Dettes et santé mentale : perspective de genre

Author

Caroline Henchoz, Boris Wernli, and Tristan Coste

Subjects
mental health, inequalities, longitudinal analysis, panel, debt, gender., Sociology (General), HM401-1281
Abstract

The effect of debt on health remains little studied, and the gender perspective is rarely mobilized. This article aims to better understand the gendered effect of arrears - a particularly problematic and prevalent type of debt - on the mental health of women and men by testing different explanatory hypotheses. Using data from the Swiss Household Panel, we show that women in debt have the poorest mental health, but that the occurrence of arrears does not affect them more than men. However, certain sub-groups of women are more affected. In this sense, the gendered effect of debt on mental health is more related to an accumulation of social inequalities than to the existence of gendered dispositions towards debt, which underlines the interest of the intersectional approach.

Published
2024
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159. Upc2-mediated mechanisms of azole resistance in Candida auris

Author

Jizhou Li, Lola Aubry, Danielle Brandalise, Alix T. Coste, Dominique Sanglard, and Frederic Lamoth

Subjects
ergosterol, efflux pumps, antifungal resistance, zinc cluster transcription factor, Candida albicans, Candida glabrata, Microbiology, QR1-502
Abstract

ABSTRACTCandida auris is an emerging yeast pathogen of major concern because of its ability to cause hospital outbreaks of invasive candidiasis and to develop resistance to antifungal drugs. A majority of C. auris isolates are resistant to fluconazole, an azole drug used for the treatment of invasive candidiasis. Mechanisms of azole resistance are multiple, including mutations in the target gene ERG11 and activation of the transcription factors Tac1b and Mrr1, which control the drug transporters Cdr1 and Mdr1, respectively. We investigated the role of the transcription factor Upc2, which is known to regulate the ergosterol biosynthesis pathway and azole resistance in other Candida spp. Genetic deletion and hyperactivation of Upc2 by epitope tagging in C. auris resulted in drastic increases and decreases in susceptibility to azoles, respectively. This effect was conserved in strains with genetic hyperactivation of Tac1b or Mrr1. Reverse transcription PCR analyses showed that Upc2 regulates ERG11 expression and also activates the Mrr1/Mdr1 pathway. We showed that upregulation of MDR1 by Upc2 could occur independently from Mrr1. The impact of UPC2 deletion on MDR1 expression and azole susceptibility in a hyperactive Mrr1 background was stronger than that of MRR1 deletion in a hyperactive Upc2 background. While Upc2 hyperactivation resulted in a significant increase in the expression of TAC1b, CDR1 expression remained unchanged. Taken together, our results showed that Upc2 is crucial for azole resistance in C. auris, via regulation of the ergosterol biosynthesis pathway and activation of the Mrr1/Mdr1 pathway. Notably, Upc2 is a very potent and direct activator of Mdr1.IMPORTANCECandida auris is a yeast of major medical importance causing nosocomial outbreaks of invasive candidiasis. Its ability to develop resistance to antifungal drugs, in particular to azoles (e.g., fluconazole), is concerning. Understanding the mechanisms of azole resistance in C. auris is important and may help in identifying novel antifungal targets. This study shows the key role of the transcription factor Upc2 in azole resistance of C. auris and shows that this effect is mediated via different pathways, including the regulation of ergosterol biosynthesis and also the direct upregulation of the drug transporter Mdr1.

Published
2024
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160. Cancer selective cell death induction by a bivalent CK2 inhibitor targeting the ATP site and the allosteric αD pocket

Author

Alexandre Bancet, Rita Frem, Florian Jeanneret, Angélique Mularoni, Pauline Bazelle, Caroline Roelants, Jean-Guy Delcros, Jean-François Guichou, Catherine Pillet, Isabelle Coste, Toufic Renno, Christophe Battail, Claude Cochet, Thierry Lomberget, Odile Filhol, and Isabelle Krimm

Subjects
Molecular biology, Cell biology, Structural biology, Cancer, Science
Abstract

Summary: Although the involvement of protein kinase CK2 in cancer is well-documented, there is a need for selective CK2 inhibitors suitable for investigating CK2 specific roles in cancer-related biological pathways and further exploring its therapeutic potential. Here, we report the discovery of AB668, an outstanding selective inhibitor that binds CK2 through a bivalent mode, interacting both at the ATP site and an allosteric αD pocket unique to CK2. Using caspase activation assay, live-cell imaging, and transcriptomic analysis, we have compared the effects of this bivalent inhibitor to representative ATP-competitive inhibitors, CX-4945, and SGC-CK2-1. Our results show that in contrast to CX-4945 or SGC-CK2-1, AB668, by targeting the CK2 αD pocket, has a distinct mechanism of action regarding its anti-cancer activity, inducing apoptotic cell death in several cancer cell lines and stimulating distinct biological pathways in renal cell carcinoma.

Published
2024
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161. The role of antibody responses against glycans in bioprosthetic heart valve calcification and deterioration

Author

Senage, Thomas, Paul, Anu, Le Tourneau, Thierry, Fellah-Hebia, Imen, Vadori, Marta, Bashir, Salam, Galiñanes, Manuel, Bottio, Tomaso, Gerosa, Gino, Evangelista, Arturo, Badano, Luigi P, Nassi, Alberto, Costa, Cristina, Cesare, Galli, Manji, Rizwan A, Cueff de Monchy, Caroline, Piriou, Nicolas, Capoulade, Romain, Serfaty, Jean-Michel, Guimbretière, Guillaume, Dantan, Etienne, Ruiz-Majoral, Alejandro, Coste du Fou, Guénola, Leviatan Ben-Arye, Shani, Govani, Liana, Yehuda, Sharon, Bachar Abramovitch, Shirley, Amon, Ron, Reuven, Eliran Moshe, Atiya-Nasagi, Yafit, Yu, Hai, Iop, Laura, Casós, Kelly, Kuguel, Sebastián G, Blasco-Lucas, Arnau, Permanyer, Eduard, Sbraga, Fabrizio, Llatjós, Roger, Moreno-Gonzalez, Gabriel, Sánchez-Martínez, Melchor, Breimer, Michael E, Holgersson, Jan, Teneberg, Susann, Pascual-Gilabert, Marta, Nonell-Canals, Alfons, Takeuchi, Yasuhiro, Chen, Xi, Mañez, Rafael, Roussel, Jean-Christian, Soulillou, Jean-Paul, Cozzi, Emanuele, and Padler-Karavani, Vered

Subjects
Biomedical and Clinical Sciences, Immunology, Heart Disease, Cardiovascular, 5.3 Medical devices, Development of treatments and therapeutic interventions, Animals, Antibody Formation, Aortic Valve, Aortic Valve Stenosis, Bioprosthesis, Calcinosis, Galactose, Humans, Immunoglobulin G, Mice, Polysaccharides, Prospective Studies, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract

Bioprosthetic heart valves (BHVs) are commonly used to replace severely diseased heart valves but their susceptibility to structural valve degeneration (SVD) limits their use in young patients. We hypothesized that antibodies against immunogenic glycans present on BHVs, particularly antibodies against the xenoantigens galactose-α1,3-galactose (αGal) and N-glycolylneuraminic acid (Neu5Gc), could mediate their deterioration through calcification. We established a large longitudinal prospective international cohort of patients (n = 1668, 34 ± 43 months of follow-up (0.1-182); 4,998 blood samples) to investigate the hemodynamics and immune responses associated with BHVs up to 15 years after aortic valve replacement. Early signs of SVD appeared in

Published
2022

164. Sparse matrices: convergence of the characteristic polynomial seen from infinity

Author

Coste, Simon

Subjects
Mathematics - Probability, 05C80, 15B52, 30B20
Abstract

We prove that the reverse characteristic polynomial $\det(I_n - zA_n)$ of a random $n \times n$ matrix $A_n$ with iid $\mathrm{Bernoulli}(d/n)$ entries converges in distribution towards the random infinite product $\prod_{\ell = 1}^\infty(1-z^\ell)^{Y_\ell}$ where $Y_\ell$ are independent $\mathrm{Poisson}(d^\ell/\ell)$ random variables. We show that this random function is a Poisson analog of more classical Gaussian objects such as the Gaussian holomorphic chaos. As a byproduct, we obtain new simple proofs of previous results on the asymptotic behaviour of extremal eigenvalues of sparse Erd\H{o}s-R\'enyi digraphs: for every $d>1$, the greatest eigenvalue of $A_n$ is close to $d$ and the second greatest is smaller than $\sqrt{d}$, a Ramanujan-like property for irregular digraphs. For $d<1$, the only non-zero eigenvalues of $A_n$ converge to a Poisson multipoint process on the unit circle. Our results also extend to the semi-sparse regime where $d$ is allowed to grow to $\infty$ with $n$, slower than $n^{o(1)}$. We show that the reverse characteristic polynomial converges towards a more classical object written in terms of the exponential of a log-correlated real Gaussian field, as in the dense case studied in a recent paper \cite{bordenave2020convergence}. In the semi-sparse regime, the empirical spectral distribution of $A_n/\sqrt{d_n}$ converges to the circle distribution; as a consequence of our results, the second eigenvalue sticks to the edge of the circle., Comment: Added the semi-sparse case $d_n \to \infty$ and a more complete description of the $d_n=d<1$ case

Published
2021

166. Is Metagenomics the Future Routine Diagnosis Tool for Brain Abscesses? About a Case

Author

William Lars, Claudie Lamoureux, Jérémy Picard, Christophe Rodriguez, Clémence Beauruelle, Luc Quaesaet, Geneviève Héry-Arnaud, Séverine Ansart, and Anne Coste

Subjects
brain abscess, shotgun metagenomics, sequencing, microbiological documentation, Biology (General), QH301-705.5
Abstract

Shotgun metagenomics (SMg) usefulness for brain abscess diagnosis is not known. We describe a case of brain abscess diagnosed with SMg and provide a review of the literature. A 70-year-old woman was diagnosed with multiple brain abscesses. Standard culture techniques and 16S rRNA gene sequencing of abscess samples remained negative. SMg finally revealed the presence of sequences from Streptococcus anginosus and Fusobacterium nucleatum, leading to antimicrobial treatment adaptation and corticosteroids initiation. The patient finally recovered. A literature review retrieved fifteen other cases of brain abscesses diagnosed with SMg. SMg results led to changes in patient management in most cases. The existing literature about the performances of SMg, its advantages, future evolutions, and limitations is then discussed. SMg place in routine should be evaluated and defined through prospective studies.

Published
2023
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168. Référentiel national de traitement des carcinomes épidermoïdes des voies aérodigestives supérieures – Principes généraux de traitement

Author

Barry, Béatrix, Dolivet, Gilles, Clatot, Florian, Huguet, Florence, Abdeddaim, Cyril, Baujat, Bertrand, Blanchard, Nicolas, Calais, Gilles, Carrat, Xavier, Chatellier, Anne, Coste, Florence, Cupissol, Didier, Cuvelier, Philippe, De Mones Del Pujol, Erwan, Deneuve, Sophie, Duffas, Olivier, Dupret-Bories, Agnès, Even, Caroline, Evrard, Camille, Evrard, Diane, Faivre, Sandrine, Fakhry, Nicolas, Garrel, Renaud, Gorphe, Philippe, Houliat, Thierry, Kaminsky, Marie-Christine, Krebs, Lorraine, Lapeyre, Michel, Lindas, Pierre, Malard, Olivier, Mirghani, Haitham, Mondina, Michel, Moriniere, Sylvain, Mouawad, François, Pestre-Munier, Julia, Pham Dang, Nathalie, Picard, Annabelle, Ramin, Lionel, Renard, Sophie, Salvan, Didier, Schernberg, Antoine, Sire, Christian, Thariat, Juliette, Vanbockstael, Julie, Vo Tan, Dan, Wojcik, Thomas, Klein, Isabelle, Block, Véronique, Baumann-Bouscaud, Lorraine, and De Raucourt, Dominique

Published
2024
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178. A simpler spectral approach for clustering in directed networks

Author

Coste, Simon and Stephan, Ludovic

Subjects
Computer Science - Machine Learning, Mathematics - Probability
Abstract

We study the task of clustering in directed networks. We show that using the eigenvalue/eigenvector decomposition of the adjacency matrix is simpler than all common methods which are based on a combination of data regularization and SVD truncation, and works well down to the very sparse regime where the edge density has constant order. Our analysis is based on a Master Theorem describing sharp asymptotics for isolated eigenvalues/eigenvectors of sparse, non-symmetric matrices with independent entries. We also describe the limiting distribution of the entries of these eigenvectors; in the task of digraph clustering with spectral embeddings, we provide numerical evidence for the superiority of Gaussian Mixture clustering over the widely used k-means algorithm., Comment: 42 pages

Published
2021

179. Pressure-Controlled Intermittent Coronary Sinus Occlusion (PiCSO) in Acute Myocardial Infarction: The PiCSO-AMI-I Trial

Author

De Maria, Giovanni Luigi, Greenwood, John P., Zaman, Azfar G., Carrié, Didier, Coste, Pierre, Valgimigli, Marco, Behan, Miles, Berry, Colin, Erglis, Andrejs, Panoulas, Vasileios F., Van Belle, Eric, Juhl Terkelsen, Christian, Hunziker Munsch, Lukas, Jain, Ajay K., Lassen, Jens Flensted, Palmer, Nick, Stone, Gregg W., and Banning, Adrian P.

Published
2024
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181. Rough Hypoellipticity for the Heat Equation in Dirichlet Spaces

Author

Hou, Qi and Saloff-Coste, Laurent

Subjects
Mathematics - Analysis of PDEs, Mathematics - Functional Analysis, Mathematics - Probability
Abstract

This paper aims at proving the local boundedness and continuity of solutions of the heat equation in the context of Dirichlet spaces under some rather weak additional assumptions. We consider symmetric local regular Dirichlet forms which satisfy mild assumptions concerning (a) the existence of cut-off functions, (b) a local ultracontractivity hypothesis, and (c) a weak off-diagonal upper bound. In this setting, local weak solutions of the heat equation, and their time derivatives, are shown to be locally bounded; they are further locally continuous, if the semigroup admits a locally continuous density function. Applications of the results are provided including discussion on the existence of locally bounded heat kernel; $L^\infty$ structure results for ancient solutions of the heat equation. The last section presents a special case where the $L^\infty$ off-diagonal upper bound follows from the ultracontractivity property of the semigroup. This paper is a continuation of [7].

Published
2020

187. The 4-Player Gambler’s Ruin Problem

Author

O’Connor, Kathryn, Saloff-Coste, Laurent, Benedetto, John J., Series Editor, Czaja, Wojciech, Series Editor, Okoudjou, Kasso, Series Editor, Aldroubi, Akram, Editorial Board Member, Casazza, Peter, Editorial Board Member, Cochran, Douglas, Editorial Board Member, Feichtinger, Hans G., Editorial Board Member, Gilbert, Anna C., Editorial Board Member, Heil, Christopher, Editorial Board Member, Jaffard, Stéphane, Editorial Board Member, Kutyniok, Gitta, Editorial Board Member, Maggioni, Mauro, Editorial Board Member, Molter, Ursula, Editorial Board Member, Shen, Zuowei, Editorial Board Member, Strohmer, Thomas, Editorial Board Member, Unser, Michael, Editorial Board Member, Wang, Yang, Editorial Board Member, Alonso Ruiz, Patricia, editor, Hinz, Michael, editor, Okoudjou, Kasso A., editor, Rogers, Luke G., editor, and Teplyaev, Alexander, editor

Published
2023
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190. Transthyretin amyloid cardiomyopathy in France: A cross-sectional multi-centre study (333 patients)

Author

Damy, Thibaud, Donal, Erwan, Lairez, Olivier, Eicher, Jean-Christophe, Karoubi, Mounira, Trochu, Jean-Noël, Inamo, Jocelyn, Habib, Gilbert, Roubille, François, Hagège, Albert, Morio, Flore, Cariou, Eve, Adda, Jérôme, Algalarrondo, Vincent, Coste, Agathe, Bartoli, Mathilde, Rudant, Jérémie, Salvi, Lara, Francou, Bruno, Guiochon-Mantel, Anne, Adams, David, Antoine, Jean-Christophe, Attarian, Shahram, Cintas, Pascal, Morales, Raul Juntas, Lagrange, Emmeline, Magy, Laurent, Mallaret, Martial, Péréon, Yann, Petiot, Philippe, Cauquil, Cécile, Labeyrie, Céline, Echaniz-Laguna, Andoni, Sole, Guilhem, Tard, Céline, Oghina, Silvia, Charron, Philippe, and Slama, Michel

Published
2024
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191. Current state-of-the-art and gaps in platform trials: 10 things you should know, insights from EU-PEARL

Author

Sánchez-Montalva, Adrian, Estevez, Ana Belén, Sánchez, Àlex, Sanjuan, Anna, Sena, Elena, Granados, Emma, Arévalo de Andrés, Esther, Nuñez, Fátima, Arteaga, Gara, Fuentes Ruiz, Gabriela Perez, Fernández, Guillermo, Rivera-Esteban, Jesus, Comella, Joan, Ramos-Quiroga, Josep Antoni, Genescà, Joan, Espinosa, Juan, Pericàs, Juan Manuel, Murcia, Lada, Cash-Gibson, Lucinda, de Valles Silvosa, Maria, Barroso de Sousa, María Fernanda, Sánchez-Maroto Carrizo, Olga, Ibañez-Jiménez, Pol, Augustin, Salvador, Perez-Hoyos, Santiago, Rodríguez-Navarro, Sarai, Muñoz-Martínez, Sergio, Serres, Silvia, Kalko, Susana, Michon, Amelie, Ussi, Anton, Lydall, Ben, van de Ketterij, Edwin, Quiles, Ignacio, Carapina, Tamara, Kumaus, Constantin, Ramazanova, Dariga, Meyer, Elias Laurin, Koenig, Franz, Roig, Marta Bofill, Brunner, Martin, Posch, Martin, Krotka, Pavla, Zehetmayer, Sonja, Carton, Charlotte, Legius, Eric, Begum, Amina, Pariante, Carmine, Worrell, Courtney, Lombardo, Giulia, Sforzini, Luca, Brown, Mollie, Gullet, Nancy, Amasi-Hartoonian, Nare, Ferner, Rosalie, Kose, Melisa, Spitaleri, Andrea, Ghodousi, Arash, Di Serio, Clelia, Cirillo, Daniela, Cugnata, Federica, Saluzzo, Francesca, Benedetti, Francesco, Scarale, Maria Giovanna, Zini, Michela, Rancoita, Paola Maria, Alagna, Riccardo, Poletti, Sara, Dhaenens, Britt, Van Der Lei, Johan, de Steenwinkel, Jurriaan, Moinat, Maxim, Oostenbrink, Rianne, Hoogendijk, Witte, Hölscher, Michael, Heinrich, Norbert, Otte, Christian, Potratz, Cornelia, Zocholl, Dario, Kulakova, Eugenia, Tacke, Frank, Brasanac, Jelena, Leubner, Jonas, Krajewska, Maja, Freitag, Michaela Maria, Gold, Stefan, Zoller, Thomas, Chae, Woo Ri, Daniel, Christel, Kara, Leila, Vaterkowski, Morgan, Griffon, Nicolas, Wolkenstein, Pierre, Pais, Raluca, Ratziu, Vlad, Voets, David, Maes, Christophe, Kalra, Dipak, Thienpoint, Geert, Deckerck, Jens, Lea, Nathan, Singleton, Peter, Viele, Kert, Jacko, Peter, Berry, Scott, Parke, Tom, Aydin, Burç, Kubiak, Christine, Demotes, Jacques, Ueda, Keiko, Matei, Mihaela, Contrino, Sergio, Röhl, Claas, Cordero, Estefania, Greenhalgh, Fiona, Jarke, Hannes, Angelova, Juliana, Boudes, Mathieu, Dressler, Stephan, Strammiello, Valentina, Anstee, Quentin, Gutierrez-Ibarluzea, Iñaki, Otte, Maximilian, Heimbach, Natalie, Hofner, Benjamin, Burgwinkel, Cora, Kaestel, Hue, Hees, Katharina, Nguyen, Quynh, Prieto-Alhambra, Daniel, Tan, Eng Hooi (Cheryl), Raviglione, Mario, de Colombani, Pierpaolo, Villa, Simone, Maron, Eduard, Evans, Gareth, Savitz, Adam J., Van Dessel, Ann, Duca, Anna, Kaminski, Anne, Wouters, Bie, Porter, Brandon, Charron, Catherine, Spiertz, Cecile, Zizzamia, Christopher, Millar, Daniel, Hasselbaink, Danny, Orr, David, Kesters, Divya, Hubin, Ellen, Davies, Emma, Didden, Eva-Maria, Guz, Gabriela, Verstraete, Evelyn, Mao, Gary, Capuano, George, Martynowicz, Heddie, De Smedt, Heidi, Larsson, Ingela, Bruegelmans, Ines, Coste, Isabelle, Gonzalez Moreno, Jesus Maria, Niewczas, Julia, Xu, Jiajun, Rombouts, Karin, Woo, Katherine, Wuyts, Kathleen, Hersh, Kathryn, Oldenburg, Khrista, Zhang, Lingjiao, Schmidt, Mark, Szuch, Mark, Todorovic, Marija, Mangelaars, Maartje, Grewal, Melissa, Sandor, Molli, Di Prospero, Nick, Van Houten, Pamela, Minnick, Pansy, Bastos, Polyana, Patrizi, Robert, Morello, Salvatore, De Wilde, Severijn, Sun, Tao, Kline, Timothy, de Marez, Tine, Mielke, Tobias, Reijns, Tom, Popova, Vanina, Flossbach, Yanina, Tymofyeyev, Yevgen, De Groote, Zeger, Sverdlov, Alex, Bobirca, Alexandra, Krause, Annekatrin, Bobrica, Catalin, Heintz, Daniela, Magirr, Dominic, Glimm, Ekkehard, Baffert, Fabienne, Castiglione, Federica, Caruso, Franca, Patalano, Francesco, Bretz, Frank, Heimann, Guenter, Carbarns, Ian, Rodríguez, Ignacio, Ratescu, Ioana, Hampson, Lisa, Pedrosa, Marcos, Hark, Mareile, Mesenbrink, Peter, Penna, Sabina Hernandez, Bergues-Lang, Sarah, Baltes-Engler, Susanne, Arsiwala, Tasneem, Mondragon, Valeria Jordan, Guo, Hua, Da Costa, Jose Leite, Burman, Carl-Fredrik, Kirk, George, Aaes-Jørgensen, Anders, Dirach, Jorgen, Kjær, Mette Skalshøi, Martin, Alexandra, Hristov, Diyan, Rousseaux, Florent, Hittel, Norbert, Dornheim, Robert, Evans, Daniel, Sykes, Nick, Couvert, Camille, Leuven, Catherine, Notelet, Loïc, Gidh-Jain, Madhavi, Jouannin, Mathieu, Ammour, Nadir, Pierre, Suzanne, Haufe, Volker, Dong, Yingwen, Dubanchet, Catherine, de Préville, Nathalie, Baltauss, Tania, Jian, Zhu, Shnider, Sara, Bar-El, Tal, Bakker, Annette, Nievo, Marco, Iloeje, Uche, Conradie, Almari, Auffarrth, Ece, Lombard, Leandra, Benhayoun, Majda, Olugbosi, Morounfolu, Seidel, Stephanie S., Gumí, Berta, Guzmán, Claudia García, Molero, Eva, Pairó, Gisela, Machin, Núria, Cardelús, Raimon, Ramasastry, Saira, Pelzer, Saskia, Kremer, Andreas, Lindfors, Erno, Lynch, Chris, Spiertz, Cécile, Machín, Núria, and Pericàs, Juan M.

Published
2024
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195. Social and clinical vulnerability in stroke and STEMI management during the COVID-19 pandemic: a registry-based study

Author

Jérome Berge, Gaultier Marnat, Emmanuel Ellie, Igor Sibon, Basile Ondze, Ludovic Lucas, Xavier Combes, Catherine Pradeau, Pierre Coste, Jean-Luc Banos, Nicolas Delarche, François Rouanet, Pierre Fournier, Patricia Bernady, David Higue, Julie Péron, Stephanie Bannier, Virginie Heydel, Nathalie Goulois, Francois Orcival, Stephanie Vandentorren, Jean-Louis Leymarie, Bernard Karsenty, Emilie Lesaine, Sandrine Domecq, Laura Cetran, Sahal Miganeh-Hadi, Floriane Sevin, Stéphanie Demasles, Régis Hubrecht, Florence Francis, Florence Saillour, Jean Faucheux, Elena Leca Radu, Gaëlle Seignolles, Cécile Chazalon, Maria Dan, Laurent Wong-So, Miquel Martinez, Claire Nocon, Véronique Hostyn, Jérémy Papin, Philippe Bordier, Philippe Casenave, Laurent Maillard, Isabelle Argacha, Eliane Tidahy, Lucie Ferraton, Yousra Mostefai, Djoumana Bakpa, Christine Bartou, Catherine Goze-Dupuy, Hélène Lavocat, Frédéric Senis, Virginie Delonglee, Didier Darraillans, Tarak Mokni, Bertrand Bataille, Jean Lorendeau, Anncy Eclancher, Bruno Trogoff, Véronique Chartroule, Philippe Touchard, Hervé Leyral, Fogue Ngounou, Catherine Scouarnec, Bertrand Tahon, Emmanuel Py, Sorina Bidian, Jean Fabre, Nidhal Cherhabil, Leila Baha, Pierre-Arnaud Fort, Vincent Maisonnave, Luc Verhoeven, Paul Claveries, Emma Ansart, Brice Lefevre, Marie-Pierre Liepa, Marc Lacrouts, Jean-Baptiste Coustere, Philippe Jarnier, Nicolas Marque, Jean-Marie Perron, Akil Hassan, Francois Casteigt, Bernard Larnaudie, and Guillaume Laplace

Subjects
Medicine
Abstract

Objective This study aims to evaluate whether the first wave of the COVID-19 pandemic resulted in a deterioration in the quality of care for socially and/or clinically vulnerable stroke and ST-segment elevation myocardial infarction (STEMI) patients.Design Two cohorts of STEMI and stroke patients in the Aquitaine neurocardiovascular registry.Setting Six emergency medical services, 30 emergency units, 14 hospitalisation units and 11 catheterisation laboratories in the Aquitaine region in France.Participants This study involved 9218 patients (6436 stroke and 2782 STEMI patients) in the neurocardiovascular registry from January 2019 to August 2020.Primary outcome measures Care management times in both cohorts: first medical contact-to-procedure time for the STEMI cohort and emergency unit admission-to-imaging time for the stroke cohort. Associations between social (deprivation index) and clinical (age >65 years, neurocardiovascular history) vulnerabilities and care management times were analysed using multivariate linear mixed models, with an interaction on the time period (pre-wave, per-wave and post-first COVID-19 wave).Results The first medical contact procedure time was longer for elderly (p

Published
2024
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196. Water security risks in small, remote, indigenous communities in Canada: A critical review on challenges and opportunities

Author

Michael De Coste, Sana Saleem, Haroon R. Mian, Gyan Chhipi-Shrestha, Kasun Hewage, Madjid Mohseni, and Rehan Sadiq

Subjects
indigenous communities, risk assessment, risk management, decision-making, water security, Environmental sciences, GE1-350, Hydraulic engineering, TC1-978
Abstract

Indigenous communities in Canada are disproportionately affected by issues related to water security, especially access to clean water to meet human needs. The issues these communities face are diverse and widespread across Canada, with many causes and consequences. This review summarizes the types and magnitudes of risks associated with the water security of these communities, the consequences considering health and social perspectives, and the means of responding to these issues. Risks are broadly divided into quantitative risks (e.g., water quality and availability) and qualitative risks (e.g., lack of funding and jurisdictional conflicts). These risks lead to unique consequences, resulting in challenges in developing generalized risk response frameworks. Management of these risks includes a mix of techniques relying on legislative and technical approaches. Nevertheless, the affected communities should be included in the decision-making process that should be holistic, incorporating indigenous knowledge. Good governance, cooperation between communities, policy improvement and the development of an institutional mechanism for clean water supply will provide a pathway and guidelines to address the water security challenges among indigenous communities.

Published
2024
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197. Parental occupations at birth and risk of adult testicular germ cell tumors in offspring: a French nationwide case–control study

Author

Adèle Paul, Aurélie M. N. Danjou, Floriane Deygas, Margot Guth, Astrid Coste, Marie Lefevre, Brigitte Dananché, Hans Kromhout, Johan Spinosi, Rémi Béranger, Olivia Pérol, Helen Boyle, Christel Hersant, Vanessa Loup-Cabaniols, Ségolène Veau, Louis Bujan, Ann Olsson, Joachim Schüz, Béatrice Fervers, and Barbara Charbotel

Subjects
testicular cancer, testicular germ cell tumor, parental occupational exposure, prenatal exposure, parental job, parental occupation, Public aspects of medicine, RA1-1270
Abstract

BackgroundTesticular germ cell tumors (TGCT) are the most frequent cancer in young men in developed countries. Parental occupational exposures during early-life periods are suspected to increase TGCT risk. The objective was to estimate the association between parental occupations at birth and adult TGCT.MethodsA case–control study was conducted, including 454 TGCT cases aged 18–45 from 20 French university hospitals, matched to 670 controls based on region and year of birth. Data collected from participants included parental jobs at birth coded according to the International Standard Classification of Occupation—1968 and the French nomenclature of activities—1999. Odds ratios (OR) for TGCT and 95% confidence intervals (CI) were estimated using conditional logistic regression, adjusting for TGCT risk factors.ResultsPaternal jobs at birth as service workers (OR = 1.98, CI 1.18–3.30), protective service workers (OR = 2.40, CI 1.20–4.81), transport equipment operators (OR = 1.96, CI 1.14–3.37), specialized farmers (OR = 2.66, CI 1.03–6.90), and maternal jobs as secondary education teachers (OR = 2.27, CI 1.09–4.76) or in secondary education (OR = 2.35, CI 1.13–4.88) were significantly associated with adult TGCT. The risk of seminoma was increased for the above-mentioned paternal jobs and that of non-seminomas for public administration and defence; compulsory social security (OR = 1.99, CI 1.09–3.65); general, economic, and social administration (OR = 3.21, CI 1.23–8.39) for fathers; and secondary education teacher (OR = 4.67, CI 1.87–11.67) and secondary education (OR = 3.50, CI 1.36–9.01) for mothers.ConclusionSome paternal jobs, such as service workers, transport equipment operators, or specialized farmers, and maternal jobs in secondary education seem to be associated with an increased risk of TGCT with specific features depending on the histological type. These data allow hypotheses to be put forward for further studies as to the involvement of occupational exposures in the risk of developing TGCT, such as exposure to pesticides, solvents, or heavy metals.

Published
2024
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198. Current state-of-the-art and gaps in platform trials: 10 things you should know, insights from EU-PEARL

Author

Franz Koenig, Cécile Spiertz, Daniel Millar, Sarai Rodríguez-Navarro, Núria Machín, Ann Van Dessel, Joan Genescà, Juan M. Pericàs, Martin Posch, Adrian Sánchez-Montalva, Ana Belén Estevez, Àlex Sánchez, Anna Sanjuan, Elena Sena, Emma Granados, Esther Arévalo de Andrés, Fátima Nuñez, Gara Arteaga, Gabriela Perez Fuentes Ruiz, Guillermo Fernández, Jesus Rivera-Esteban, Joan Comella, Josep Antoni Ramos-Quiroga, Juan Espinosa, Juan Manuel Pericàs, Lada Murcia, Lucinda Cash-Gibson, Maria de Valles Silvosa, María Fernanda Barroso de Sousa, Olga Sánchez-Maroto Carrizo, Pol Ibañez-Jiménez, Salvador Augustin, Santiago Perez-Hoyos, Sergio Muñoz-Martínez, Silvia Serres, Susana Kalko, Amelie Michon, Anton Ussi, Ben Lydall, Edwin van de Ketterij, Ignacio Quiles, Tamara Carapina, Constantin Kumaus, Dariga Ramazanova, Elias Laurin Meyer, Marta Bofill Roig, Martin Brunner, Pavla Krotka, Sonja Zehetmayer, Charlotte Carton, Eric Legius, Amina Begum, Carmine Pariante, Courtney Worrell, Giulia Lombardo, Luca Sforzini, Mollie Brown, Nancy Gullet, Nare Amasi-Hartoonian, Rosalie Ferner, Melisa Kose, Andrea Spitaleri, Arash Ghodousi, Clelia Di Serio, Daniela Cirillo, Federica Cugnata, Francesca Saluzzo, Francesco Benedetti, Maria Giovanna Scarale, Michela Zini, Paola Maria Rancoita, Riccardo Alagna, Sara Poletti, Britt Dhaenens, Johan Van Der Lei, Jurriaan de Steenwinkel, Maxim Moinat, Rianne Oostenbrink, Witte Hoogendijk, Michael Hölscher, Norbert Heinrich, Christian Otte, Cornelia Potratz, Dario Zocholl, Eugenia Kulakova, Frank Tacke, Jelena Brasanac, Jonas Leubner, Maja Krajewska, Michaela Maria Freitag, Stefan Gold, Thomas Zoller, Woo Ri Chae, Christel Daniel, Leila Kara, Morgan Vaterkowski, Nicolas Griffon, Pierre Wolkenstein, Raluca Pais, Vlad Ratziu, David Voets, Christophe Maes, Dipak Kalra, Geert Thienpoint, Jens Deckerck, Nathan Lea, Peter Singleton, Kert Viele, Peter Jacko, Scott Berry, Tom Parke, Burç Aydin, Christine Kubiak, Jacques Demotes, Keiko Ueda, Mihaela Matei, Sergio Contrino, Claas Röhl, Estefania Cordero, Fiona Greenhalgh, Hannes Jarke, Juliana Angelova, Mathieu Boudes, Stephan Dressler, Valentina Strammiello, Quentin Anstee, Iñaki Gutierrez-Ibarluzea, Maximilian Otte, Natalie Heimbach, Benjamin Hofner, Cora Burgwinkel, Hue Kaestel, Katharina Hees, Quynh Nguyen, Daniel Prieto-Alhambra, Eng Hooi (Cheryl) Tan, Mario Raviglione, Pierpaolo de Colombani, Simone Villa, Eduard Maron, Gareth Evans, Adam J. Savitz, Anna Duca, Anne Kaminski, Bie Wouters, Brandon Porter, Catherine Charron, Cecile Spiertz, Christopher Zizzamia, Danny Hasselbaink, David Orr, Divya Kesters, Ellen Hubin, Emma Davies, Eva-Maria Didden, Gabriela Guz, Evelyn Verstraete, Gary Mao, George Capuano, Heddie Martynowicz, Heidi De Smedt, Ingela Larsson, Ines Bruegelmans, Isabelle Coste, Jesus Maria Gonzalez Moreno, Julia Niewczas, Jiajun Xu, Karin Rombouts, Katherine Woo, Kathleen Wuyts, Kathryn Hersh, Khrista Oldenburg, Lingjiao Zhang, Mark Schmidt, Mark Szuch, Marija Todorovic, Maartje Mangelaars, Melissa Grewal, Molli Sandor, Nick Di Prospero, Pamela Van Houten, Pansy Minnick, Polyana Bastos, Robert Patrizi, Salvatore Morello, Severijn De Wilde, Tao Sun, Timothy Kline, Tine de Marez, Tobias Mielke, Tom Reijns, Vanina Popova, Yanina Flossbach, Yevgen Tymofyeyev, Zeger De Groote, Alex Sverdlov, Alexandra Bobirca, Annekatrin Krause, Catalin Bobrica, Daniela Heintz, Dominic Magirr, Ekkehard Glimm, Fabienne Baffert, Federica Castiglione, Franca Caruso, Francesco Patalano, Frank Bretz, Guenter Heimann, Ian Carbarns, Ignacio Rodríguez, Ioana Ratescu, Lisa Hampson, Marcos Pedrosa, Mareile Hark, Peter Mesenbrink, Sabina Hernandez Penna, Sarah Bergues-Lang, Susanne Baltes-Engler, Tasneem Arsiwala, Valeria Jordan Mondragon, Hua Guo, Jose Leite Da Costa, Carl-Fredrik Burman, George Kirk, Anders Aaes-Jørgensen, Jorgen Dirach, Mette Skalshøi Kjær, Alexandra Martin, Diyan Hristov, Florent Rousseaux, Norbert Hittel, Robert Dornheim, Daniel Evans, Nick Sykes, Camille Couvert, Catherine Leuven, Loïc Notelet, Madhavi Gidh-Jain, Mathieu Jouannin, Nadir Ammour, Suzanne Pierre, Volker Haufe, Yingwen Dong, Catherine Dubanchet, Nathalie de Préville, Tania Baltauss, Zhu Jian, Sara Shnider, Tal Bar-El, Annette Bakker, Marco Nievo, Uche Iloeje, Almari Conradie, Ece Auffarrth, Leandra Lombard, Majda Benhayoun, Morounfolu Olugbosi, Stephanie S. Seidel, Berta Gumí, Claudia García Guzmán, Eva Molero, Gisela Pairó, Núria Machin, Raimon Cardelús, Saira Ramasastry, Saskia Pelzer, Andreas Kremer, Erno Lindfors, and Chris Lynch

Subjects
Adaptive designs, Master protocols, Patient-centred, Clinical research, Integrated research platform, Medicine (General), R5-920
Abstract

Summary: Platform trials bring the promise of making clinical research more efficient and more patient centric. While their use has become more widespread, including their prominent role during the COVID-19 pandemic response, broader adoption of platform trials has been limited by the lack of experience and tools to navigate the critical upfront planning required to launch such collaborative studies. The European Union-Patient-cEntric clinicAl tRial pLatform (EU-PEARL) initiative has produced new methodologies to expand the use of platform trials with an overarching infrastructure and services embedded into Integrated Research Platforms (IRPs), in collaboration with patient representatives and through consultation with U.S. Food and Drug Administration and European Medicines Agency stakeholders. In this narrative review, we discuss the outlook for platform trials in Europe, including challenges related to infrastructure, design, adaptations, data sharing and regulation. Documents derived from the EU-PEARL project, alongside a literature search including PubMed and relevant grey literature (e.g., guidance from regulatory agencies and health technology agencies) were used as sources for a multi-stage collaborative process through which the 10 more important points based on lessons drawn from the EU-PEARL project were developed and summarised as guidance for the setup of platform trials. We conclude that early involvement of critical stakeholder such as regulatory agencies or patients are critical steps in the implementation and later acceptance of platform trials. Addressing these gaps will be critical for attaining the full potential of platform trials for patients. Funding: Innovative Medicines Initiative 2 Joint Undertaking with support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.

Published
2024
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199. Complex association between post-COVID-19 condition and anxiety and depression symptoms

Author

Sarah Tebeka, Laure Carcaillon-Bentata, Valentina Decio, Caroline Alleaume, Nathalie Beltzer, Anne Gallay, Cédric Lemogne, Baptiste Pignon, Tatjana T. Makovski, and Joël Coste

Subjects
anxiety, depression, general population, long COVID, persistent symptoms, post-COVID-19 condition, Psychiatry, RC435-571
Abstract

Abstract Background To assess the associations between anxiety and depressive symptoms and post-COVID-19 condition (PCC) by exploring the direction of these associations and their relevance in the definition of PCC. Methods Nationwide survey among French adults, recruited between March and April, 2022, using a quota method to capture a representative sample of the general population with regard to sex, age, socioeconomic status, size of the place of residence, and region. We included all participants who met the World Health Organization (WHO) definition of PCC in addition to a random sample of participants infected with SARS-COV-2 for at least 3 months but without PCC. Self-reported anxiety and depressive symptoms, chronic anxiety and depression (for more than 3 years), and anxiety and depression were measured using the GAD-2 and PHQ-2 questionnaires, respectively. Results In a sample of 1,095 participants with PCC and 1,021 participants infected with SARS-COV-2 without PCC, 21% had self-reported anxiety and 18% self-reported depression, whereas 33% and 20% had current measured symptoms of anxiety and depression, respectively. The high prevalence of these symptoms cannot only be explained by the characterization of PCC, as only 13.4% of anxiety symptoms and 7.6% of depressive symptoms met the WHO criteria for PCC. Only one participant met the WHO criteria based on self-reported anxiety or depressive symptoms alone, as these were always combined with other symptoms in patients with PCC. Chronic symptoms were associated with PCC (aOR 1.27; 95% CI: 1.00–1.61). In addition, measured anxiety was associated with PCC (aOR = 1.29; 95% CI: 1.02–1.62). Conclusions Pre-COVID-19 chronic anxiety and depression may play a role in the development of PCC or share vulnerability factors with it. Our results challenge the inclusion of anxiety and depression in the definition of PCC.

Published
2024
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200. The hit-and-run version of top-to-random

Author

Boardman, Samuel, Rudolf, Daniel, and Saloff-Coste, Laurent

Subjects
Mathematics - Probability, 60J10
Abstract

We study an example of a {\em hit-and-run} random walk on the symmetric group $\mathbf S_n$. Our starting point is the well understood {\em top-to-random} shuffle. In the hit-and-run version, at each {\em single step}, after picking the point of insertion, $j$, uniformly at random in $\{1,\dots,n\}$, the top card is inserted in the $j$-th position $k$ times in a row where $k$ is uniform in $\{0,1,\dots,j-1\}$. The question is, does this accelerate mixing significantly or not? We show that, in $L^2$ and sup-norm, this accelerates mixing at most by a constant factor (independent of $n$). Analyzing this problem in total variation is an interesting open question., Comment: 18 pages, 2 figures

Published
2020

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