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1. New Ref-1/APE1 targeted inhibitors demonstrating improved potency for clinical applications in multiple cancer types

Author

Silpa Gampala, Hye-ran Moon, Randall Wireman, Jacqueline Peil, Sonia Kiran, Dana K. Mitchell, Kylee Brewster, Henry Mang, Andi Masters, Christine Bach, Whitney Smith-Kinnamen, Emma H. Doud, Ratan Rai, Amber L. Mosley, Sara K. Quinney, D. Wade Clapp, Chafiq Hamdouchi, James Wikel, Chi Zhang, Bumsoo Han, Millie M. Georgiadis, Mark R. Kelley, and Melissa L. Fishel

Subjects
Ref-1 redox function, Novel targeted inhibitors, Potency, Nuclear Factor kappa B (NFκB), Hypoxia Inducible Factor 1 (HIF1α), Cancers, Therapeutics. Pharmacology, RM1-950
Abstract

AP endonuclease-1/Redox factor-1 (APE1/Ref-1 or Ref-1) is a multifunctional protein that is overexpressed in most aggressive cancers and impacts various cancer cell signaling pathways. Ref-1′s redox activity plays a significant role in activating transcription factors (TFs) such as NFκB, HIF1α, STAT3 and AP-1, which are crucial contributors to the development of tumors and metastatic growth. Therefore, development of potent, selective inhibitors to target Ref-1 redox function is an appealing approach for therapeutic intervention. A first-generation compound, APX3330 successfully completed phase I clinical trial in adults with progressing solid tumors with favorable response rate, pharmacokinetics (PK), and minimal toxicity. These positive results prompted us to develop more potent analogs of APX3330 to effectively target Ref-1 in solid tumors. In this study, we present structure-activity relationship (SAR) identification and validation of lead compounds that exhibit a greater potency and a similar or better safety profile to APX3330. In order to triage and characterize the most potent and on-target second-generation Ref-1 redox inhibitors, we assayed for PK, mouse and human S9 fraction metabolic stability, in silico ADMET properties, ligand-based WaterLOGSY NMR measurements, pharmacodynamic markers, cell viability in multiple cancer cell types, and two distinct 3-dimensional (3D) cell killing assays (Tumor-Microenvironment on a Chip and 3D spheroid). To characterize the effects of Ref-1 inhibition in vivo, global proteomics was used following treatment with the top four analogs. This study identified and characterized more potent inhibitors of Ref-1 redox function (that outperformed APX3330 by 5–10-fold) with PK studies demonstrating efficacious doses for translation to clinic.

Published
2024
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3. Neural Correlates of Adolescent Irritability and Its Comorbidity With Psychiatric Disorders

Author

Bader Chaarani, Kees-Jan Kan, Scott Mackey, Philip A. Spechler, Alexandra Potter, Tobias Banaschewski, Sabina Millenet, Arun L.W. Bokde, Uli Bromberg, Christian Büchel, Anna Cattrell, Patricia J. Conrod, Sylvane Desrivières, Herta Flor, Vincent Frouin, Jürgen Gallinat, Penny Gowland, Andreas Heinz, Bernd Ittermann, Jean-Luc Martinot, Frauke Nees, Tomáš Paus, Luise Poustka, Michael N. Smolka, Henrik Walter, Robert Whelan, Argyris Stringaris, Stephen T. Higgins, Gunter Schumann, Hugh Garavan, Robert R. Althoff, Dr. Michael Rapp, Dr. Eric Artiges, Sophia Schneider, Christine Bach, Dr. Tomas Paus, Alexis Barbot, Dr. Gareth Barker, Dr. Arun Bokde, Dr. Nora Vetter, Dr. Christian Büchel, Dr. Anna Cattrell, Patrick Constant, Dr. Hans Crombag, Katharina Czech, Dr. Jeffrey Dalley, Benjamin Decideur, Tade Spranger, Dr. Tamzin Ripley, Dr. Nadja Heym, Dr. Wolfgang Sommer, Birgit Fuchs, Dr. Jürgen Gallinat, Dr. Hugh Garavan, Dr. Rainer Spanagel, Mehri Kaviani, Dr. Bert Heinrichs, Dr. Andreas Heinz, Naresh Subramaniam, Dr. Tianye Jia, Albrecht Ihlenfeld, James Ireland, Dr. Bernd Ittermann, Dr. Patricia Conrod, Dr. Tobias Banaschewski, Jennifer Jones, Dr. Arno Klaassen, Christophe Lalanne, Dr. Dirk Lanzerath, Dr. Claire Lawrence, Dr. Hervé Lemaitre, Dr. Sylvane Desrivieres, Catherine Mallik, Dr. Karl Mann, Dr. Adam Mar, Lourdes Martinez-Medina, Dr. Jean-Luc Martinot, Eva Mennigen, Dr. Fabiana Mesquita de Carvahlo, Yannick Schwartz, Dr. Ruediger Bruehl, Kathrin Müller, Charlotte Nymberg, Dr. Mark Lathrop, Dr. Trevor Robbins, Dr. Zdenka Pausova, Dr. Jani Pentilla, Dr. Francesca Biondo, Dr. Jean-Baptiste Poline, Dr. Luise Poustka, Dr. Michael Smolka, Juliane Fröhner, Dr. Maren Struve, Dr. Steve Williams, Dr. Thomas Hübner, Semiha Aydin, John Rogers, Alexander Romanowski, Dr. Christine Schmäl, Dirk Schmidt, Stephan Ripke, Dr. Mercedes Arroyo, Dr. Florian Schubert, Dr. Yolanda Pena-Oliver, Mira Fauth-Bühler, Xavier Mignon, Dr. Robert Whelan, Dr. Claudia Speiser, Tahmine Fadai, Dr. Dai Stephens, Dr. Andreas Ströhle, Dr. Marie-Laure Paillere, Nicole Strache, David Theobald, Sarah Jurk, Dr. Helene Vulser, Ruben Miranda, Dr. Juliana Yacubilin, Alexander Genauck, Caroline Parchetka, Isabel Gemmeke, Johann Kruschwitz, Katharina Weiss, Dr. Henrik Walter, Jianfeng Feng, Dimitri Papadopoulos, Irina Filippi, Alex Ing, Dr. Barbara Ruggeri, Bing Xu, Christine Macare, Dr. Congying Chu, Eanna Hanratty, Dr. Erin Burke Quinlan, Dr. Gabriel Robert, Dr. Gunter Schumann, Dr. Tao Yu, Veronika Ziesch, and Alicia Stedman

Subjects
Neural correlates of consciousness, medicine.medical_specialty, Generalized anxiety disorder, medicine.diagnostic_test, business.industry, 05 social sciences, medicine.disease, Irritability, Comorbidity, Psychiatry and Mental health, Developmental and Educational Psychology, medicine, Major depressive disorder, 0501 psychology and cognitive sciences, Irritable Mood, medicine.symptom, Psychiatry, Functional magnetic resonance imaging, business, 050104 developmental & child psychology, Psychopathology
Abstract

Objective Irritable mood, a common and impairing symptom in psychopathology, has been proposed to underlie the developmental link between oppositional problems in youth and depression in adulthood. We examined the neural correlates of adolescent irritability in IMAGEN, a sample of 2,024 14-year-old adolescents from 5 European countries. Method The Development and Well-Being Assessment (DAWBA) was used to assess attention-deficit/hyperactivity disorder, major depressive disorder, oppositional defiant disorder, and generalized anxiety disorder. Three items from the DAWBA, selected as close matches to the Affective Reactivity Index, were used to assess irritability. Structural magnetic resonance imaging was examined using whole-brain voxel-based morphometry analysis, and functional magnetic resonance imaging was examined during a stop signal task of inhibitory control. Imaging data were included in structural equation models to examine the direct and indirect associations between irritable mood and comorbid DSM diagnoses. Results Whole-brain voxelwise analysis showed that adolescent irritable mood was associated with less gray matter volume and less neural activation underlying inhibitory control in frontal and temporal cortical areas (cluster-correction at p Conclusion This study identifies adolescent irritability as an independent construct and points to a neurobiological correlate to irritability that is an important contributing feature to many psychopathological disorders.

Published
2020

4. Effectiveness of Geriatric Assessment-Driven Interventions on Survival and Functional and Nutritional Status in Older Patients with Head and Neck Cancer: A Randomized Controlled Trial (EGeSOR)

Author

Elena Paillaud, Lydia Brugel, Chloe Bertolus, Melany Baron, Emilie Bequignon, Philippe Caillet, Thomas Schouman, Jean Lacau Saint Guily, Sophie Périé, Eric Bouvard, Marie Laurent, Didier Salvan, Laurence Chaumette, Laure de Decker, Benoit Piot, Beatrix Barry, Agathe Raynaud-Simon, Elisabeth Sauvaget, Christine Bach, Antoine Bizard, Abderrahmane Bounar, Aurelien Minard, Bechara Aziz, Eric Chevalier, Dominique Chevalier, Cedric Gaxatte, Olivier Malard, Evelyne Liuu, Sandrine Lacour, Laetitia Gregoire, Charlotte Lafont, Florence Canouï-Poitrine, Tapia, Claudia, 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), Cancer Research and Personalized Medicine - CARPEM [Paris], 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)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'ORL [Créteil], Centre Hospitalier Intercommunal de Créteil (CHIC), Centre Léon Bérard [Lyon], Service de Stomatologie et Chirurgie Maxillo-facial [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 (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), IMRB - 'Biomechanics and Respiratory Apparatus' [Créteil] (U955 Inserm - UPEC), Biomécanique & Appareil Respiratoire (BAR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Institut de Biomécanique Humaine Georges Charpak (IBHGC), Université Sorbonne Paris Nord-Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Oto-Rhino-Laryngologie Chirurgie cervico-faciale [CHU Tenon], CHU Tenon [AP-HP], Fondation Ophtalmologique Adolphe de Rothschild [Paris], Clinique Hartmann [Neuilly-sur-Seine], Hôpital Henri Mondor, Centre Hospitalier Sud Francilien, Centre hospitalier universitaire de Nantes (CHU Nantes), Pôle hospitalo-universitaire de gérontologie clinique [Nantes], Département de Stomatologie et chirurgie maxillo-faciale [CHU Nantes], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre hospitalier Saint-Joseph [Paris], Hôpital Foch [Suresnes], Centre Hospitalier Intercommunal Villeneuve-Saint-Georges (CHIV), Hôpital Léopold Bellan [Paris] (HLB), Hôpital Claude Huriez [Lille], CHU Lille, Centre hospitalier universitaire de Poitiers (CHU Poitiers), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)

Subjects
Cancer Research, function, geriatric assessment, head and neck cancer, elderly, survival, nutrition, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Oncology, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; This study assesses the efficacy of Geriatric Assessment (GA)-driven interventions and follow-up on six-month mortality, functional, and nutritional status in older patients with head and neck cancer (HNC). HNC patients aged 65 years or over were included between November 2013 and September 2018 by 15 Ear, Nose, and Throat (ENT) and maxillofacial surgery departments at 13 centers in France. The study was of an open-label, multicenter, randomized, controlled, and parallel-group design, with independent outcome assessments. The patients were randomized 1:1 to benefit from GA-driven interventions and follow-up versus standard of care. The interventions consisted in a pre-therapeutic GA, a standardized geriatric intervention, and follow-up, tailored to the cancer-treatment plan for 24 months. The primary outcome was a composite criterion including six-month mortality, functional impairment (fall in the Activities of Daily Living (ADL) score ≥2), and weight loss ≥10%. Among the patients included (n = 499), 475 were randomized to the experimental (n = 238) or control arm (n = 237). The median age was 75.3 years [70.4–81.9]; 69.5% were men, and the principal tumor site was oral cavity (43.9%). There were no statistically significant differences regarding the primary endpoint (n = 98 events; 41.0% in the experimental arm versus 90 (38.0%); p = 0.53), or for each criterion (i.e., death (31 (13%) versus 27 (11.4%); p = 0.48), weight loss of ≥10% (69 (29%) versus 65 (27.4%); p = 0.73) and fall in ADL score ≥2 (9 (3.8%) versus 13 (5.5%); p = 0.35)). In older patients with HNC, GA-driven interventions and follow-up failed to improve six-month overall survival, functional, and nutritional status.

Published
2022

5. Sustainable development outcomes of alternative consumer networks – A systematic review and logic model development

Author

Birgit Teufer, Sonja Grabner-Kräuter, and Christine Bachner

Subjects
Consumer networks, Sustainable development, Sustainability, Logic model, Systematic review, Environmental effects of industries and plants, TD194-195, Economic growth, development, planning, HD72-88
Abstract

Alternative consumer networks (ACNs) have become increasingly important for promoting sustainable development. This study provides a conceptual clarification of ACNs and systematically reviews their impact on sustainable development. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we identified 218 peer-reviewed references that report on sustainability outcomes of ACNs at different levels, including determinants of motivation, contextual changes, behavioral changes, and social, ecological, and economic impacts. Our findings demonstrate that ACNs have a multifaceted influence on sustainability, highlighting the interconnected nature of various outcomes. This holistic approach captures the broad and significant role ACNs play in advancing sustainable practices across multiple dimensions of sustainability. We synthesized these results into a comprehensive logic model, which serves as a practical tool for systematically assessing the impact of ACNs. This model helps practitioners focusing on relevant outcomes and to develop and implement effective strategies tailored to their specific contexts. Additionally, it provides researchers with a structured framework for further study, facilitating a deeper understanding of the dynamic relationships between different sustainability outcomes.

Published
2024
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6. Mucoepidermoid carcinoma of salivary glands: A French Network of Rare Head and Neck Tumors (REFCOR) prospective study of 292 cases

Author

A. Varoquaux, L. Castillo, M. Tassart, R. Jankowski, Emmanuelle Uro-Coste, F. Massip, L. Brugel, S Testelin, René-Jean Bensadoun, Olivier Mauvais, C. Bach, P. Herman, Christian-Adrien Righini, Laurent Gilain, Xavier Dufour, T. Mom, L. Laccoureye, E. Baudin, Justin Michel, Ludovic Le Taillandier de Gabory, G. Moulin, D. de Raucourt, C. Ferron, Juliette Thariat, R. Breheret, J.-M. Badet, V. Darrouzet, Bruno Devauchelle, T. Radulesco, Bertrand Baujat, V. Strunski, G. Poissonnet, Thomas Radulesco, Jean-Claude Merol, Renaud Garrel, C. Borel, A. Cosmidis, Odile Casiraghi, Dominique Chevalier, E. Serrano, Caroline Even, J.-C. Merol, P. Demez, L. Geoffrois, N. Fakhry, J.-P. Lavieille, A. Banal, J. Lacau St Guily, S. Duflo, J.-P. Bessède, B. Baujat, Marie Christine Kaminsky, F. Chabolle, Sebastien Albert, Roch Giorgi, O. Sterkers, N. Sarroul, Vianney Bastit, D. Blanchard, P. Lang, E. de Monès, P. Breton, G. Dolivet, R. Garrel, Sébastien Vergez, B. Toussaint, Anne Sudaka, A. Giovanni, G. Noel, P. Hofman, A. Bozorg-Grayeli, O. Malard, M. Housset, E. Lartigau, P. Ceruse, Valérie Costes-Martineau, C. Bertolus, Cécile Badoual, G. Andry, T. Van den Abbeele, F. Kolb, S. Faivre, F. Floret, P. Dessi, M. Juliéron, Nicolas Fakhry, J. Michel, Louis Crampette, Francois Mouawad, O. Choussy, Philippe Schultz, S. Hans, Marine Lefevre, L. Gilain, Emile Reyt, Sylvain Morinière, Philippe Herman, G. Valette, Béatrix Barry, A. Timochenko, Gilles Poissonnet, Antoine Moya-Plana, F. Veillon, S. Vergez, A. Coste, Franck Jegoux, E. Cassagnau, Christine Bach, Y. Marie Robin, B. Guerrier, E. Uro Coste, X. Leroy, Valérie Costes, Olivier Malard, F. Rolland, F. Dubrulle, A.C. Baglin, L. de Gabory, B. Ruhin, A. Girod, G. Calais, Laurie Saloner Dahan, Emmanuel Babin, J.C. Chobaut, Michel Wassef, Benjamin Lallemant, Jean-Michel Prades, C.-A. Righini, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Aix Marseille Université (AMU), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Biostatistique et technologies de l'information et de la communication (BioSTIC) - [Hôpital de la Timone - APHM] (BiosTIC ), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Toulouse [Toulouse], CHU Bordeaux [Bordeaux], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Universitaire de la Face et du Cou [Nice], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital Foch [Suresnes], CHU Lille, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), CHU Clermont-Ferrand, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire [Grenoble] (CHU), Institut Gustave Roussy (IGR), Département de cancérologie cervico-faciale [Gustave Roussy] (CCF), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), REFCOR members: S Albert, G Andry, E Babin, C Bach, J-M Badet, C Badoual, A C Baglin, A Banal, B Barry, E Baudin, B Baujat, R J Bensadoun, C Bertolus, J-P Bessède, D Blanchard, C Borel, A Bozorg-Grayeli, R Breheret, P Breton, L Brugel, G Calais, O Casiraghi, E Cassagnau, L Castillo, P Ceruse, F Chabolle, D Chevalier, J C Chobaut, O Choussy, A Cosmidis, A Coste, V Costes, L Crampette, V Darrouzet, P Demez, P Dessi, B Devauchelle, G Dolivet, F Dubrulle, S Duflo, X Dufour, S Faivre, N Fakhry, C Ferron, F Floret, L de Gabory, R Garrel, L Geoffrois, L Gilain, A Giovanni, A Girod, B Guerrier, S Hans, P Herman, P Hofman, M Housset, R Jankowski, F Jegoux, M Juliéron, M-C Kaminsky, F Kolb, J Lacau St Guily, L Laccoureye, B Lallemant, P Lang, E Lartigau, J-P Lavieille, M Lefevre, X Leroy, O Malard, F Massip, O Mauvais, J-C Merol, J Michel, T Mom, S Morinière, E de Monès, G Moulin, G Noel, G Poissonnet, J-M Prades, T Radulesco, D de Raucourt, E Reyt, C Righini, Y Marie Robin, F Rolland, B Ruhin, N Sarroul, P Schultz, E Serrano, O Sterkers, V Strunski, A Sudaka, M Tassart, S Testelin, J Thariat, A Timochenko, B Toussaint, E Uro Coste, G Valette, T Van den Abbeele, A Varoquaux, F Veillon, S Vergez, M Wassef, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Equipe IFTIM [ImViA - EA7535], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Imagerie et Vision Artificielle [Dijon] (ImViA), Université de Bourgogne (UB)-Université de Bourgogne (UB), Laboratoire Parole et Langage (LPL), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), dormoy, valerian, Pathogénèse et contrôle des infections chroniques (PCCI), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )

Subjects
medicine.medical_specialty, Multivariate analysis, [SDV]Life Sciences [q-bio], Salivary glands, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Mucoepidermoid carcinoma, Internal medicine, Diabetes mellitus, Medicine, Stage (cooking), Intermediate Grade, 030223 otorhinolaryngology, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Cancer, [PHYS]Physics [physics], business.industry, General Medicine, medicine.disease, 3. Good health, Parotid gland, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Surgery, business
Abstract

International audience; Background: To describe the characteristics of the largest European study of MEC of salivary glands and to determine the prognostic factors for overall and disease free survival.Patients and methods: Patients with MEC were prospectively included in the Réseau d'Expertise Français sur les Cancers ORL Rares (REFCOR, French Network of Rare Head and Neck Tumors) database between 2009 and 2015.Results: A total of 292 patients were included. Tumors were classified as low grade in 175 cases (60%), intermediate in 39 (13%) and high grade in 78 (27%). Median follow-up was 26 months. The 5-year OS and DFS rates were respectively 83% and 69%. In multivariate analysis, age (p = 0.004), diabetes (p = 0.02) and advanced stage (p = 0.03) were found to have a significant negative impact on OS. Diabetes (p = 0.001), alcohol consumption (p = 0.003) and advanced stage (p = 0.001) were found to have a significant negative impact on DFS. Compare to low grade, high grade tended to have a negative impact on OS (p = 0.05) and had a significant effect on DFS (0.002) while intermediate grade had no significant influence on survival. The surgical treatment had a positive impact on both OS (p = 0.00005) and DFS (p = 0.0005). Postoperative radiotherapy had no impact in multivariate analysis.Conclusion: Advanced clinical stage, high grade tumor, high age, the impossibility of carrying out a complete surgical resection, and diabetes are the main prognostic factors in this prospective series of patients with MEC. Such findings open new research perspectives on the influence of these components on initial patient care.

Published
2020

7. Cannabis-Associated Psychotic-like Experiences Are Mediated by Developmental Changes in the Parahippocampal Gyrus

Author

Tao Yu, Tianye Jia, Liping Zhu, Sylvane Desrivières, Christine Macare, Yan Bi, Arun L.W. Bokde, Erin Burke Quinlan, Andreas Heinz, Bernd Ittermann, ChuanXin Liu, Lei Ji, Tobias Banaschewski, Decheng Ren, Li Du, Binyin Hou, Herta Flor, Vincent Frouin, Hugh Garavan, Penny Gowland, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Frauke Nees, Dimitri Papadopoulos Orfanos, Qiang Luo, Congying Chu, Tomas Paus, Luise Poustka, Sarah Hohmann, Sabina Millenet, Michael N. Smolka, Nora C. Vetter, Eva Mennigen, Cai Lei, Henrik Walter, Juliane H. Fröhner, Robert Whelan, Guang He, Lin He, Gunter Schumann, Gabriel Robert, Michael Rapp, Eric Artiges, Sophia Schneider, Christine Bach, Alexis Barbot, Gareth Barker, Arun Bokde, Nora Vetter, Christian Büchel, Anna Cattrell, Patrick Constant, Hans Crombag, Katharina Czech, Jeffrey Dalley, Benjamin Decideur, Tade Spranger, Tamzin Ripley, Nadja Heym, Wolfgang Sommer, Birgit Fuchs, Jürgen Gallinat, Rainer Spanagel, Mehri Kaviani, Bert Heinrichs, Naresh Subramaniam, Albrecht Ihlenfeld, James Ireland Delosis, Patricia Conrod, Jennifer Jones, Arno Klaassen, Christophe Lalanne, Dirk Lanzerath, Claire Lawrence, Hervé Lemaitre, Sylvane Desrivieres, Catherine Mallik, Karl Mann, Adam Mar, Lourdes Martinez-Medina, Fabiana Mesquita de Carvahlo, Yannick Schwartz, Ruediger Bruehl, Kathrin Müller, Charlotte Nymberg, Mark Lathrop, Trevor Robbins, Zdenka Pausova, Jani Pentilla, Francesca Biondo, Jean-Baptiste Poline, Michael Smolka, Juliane Fröhner, Maren Struve, Steve Williams, Thomas Hübner, Uli Bromberg, Semiha Aydin, John Rogers, Alexander Romanowski, Christine Schmäl, Dirk Schmidt, Stephan Ripke, Mercedes Arroyo, Florian Schubert, Yolanda Pena-Oliver, Mira Fauth-Bühler, Xavier Mignon, Claudia Speiser, Tahmine Fadai, Dai Stephens, Andreas Ströhle, Marie-Laure Paillere, Nicole Strache, David Theobald, Sarah Jurk, Helene Vulser, Ruben Miranda, Juliana Yacubilin, Alexander Genauck, Caroline Parchetka, Isabel Gemmeke, Johann Kruschwitz, Katharina WeiB, Jianfeng Feng, Dimitri Papadopoulos, Irina Filippi, Alex Ing, Barbara Ruggeri, Bing Xu, Eanna Hanratty, Veronika Ziesch, Alicia Stedman, King‘s College London, Shanghai Jiao Tong University [Shanghai], Service NEUROSPIN (NEUROSPIN), 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), Ecole des Neurosciences de Paris Île de France (ENP), Ecole des Neurosciences de Paris, Neuroimagerie en psychiatrie (U1000), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), 2017YFC0909200, National Basic Research Program of China (973 Program), SZSM201406007, Sanming Project of Medicine in Shenzhen, Medical Research Council, National Institute for Health Research, National Institutes of Health, 16JXRZ01, Central Universities, 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, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Institut des Neurosciences Cliniques de Rennes (INCR)-CHU Pontchaillou [Rennes]-Université européenne de Bretagne - European University of Brittany (UEB)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)

Subjects
cannabis, Mediation (statistics), Marijuana Abuse, psychotic-like experiences (PLEs), Adolescent, Population, Hippocampus, deformation-based morphometry, uncus, Risk Factors, Surveys and Questionnaires, Developmental and Educational Psychology, medicine, Humans, 0501 psychology and cognitive sciences, paired designed MRI, Risk factor, education, education.field_of_study, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, biology, business.industry, 05 social sciences, medicine.disease, biology.organism_classification, Uncus, Psychiatry and Mental health, medicine.anatomical_structure, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Psychotic Disorders, Schizophrenia, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Parahippocampal Gyrus, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cannabis, business, Parahippocampal gyrus, 050104 developmental & child psychology, Clinical psychology
Abstract

International audience; Objective: Cannabis consumption during adolescence has been reported as a risk factor for psychotic-like experiences (PLEs) and schizophrenia. However, brain developmental processes associated with cannabis-related PLEs are still poorly described.Method: A total of 706 adolescents from the general population who were recruited by the IMAGEN consortium had structural magnetic resonance imaging scans at both 14 and 19 years of age. We used deformation-based morphometry to map voxelwise brain changes between the two time points, using the pairwise algorithm in SPM12b. We used an a priori region-of-interest approach focusing on the hippocampus/parahippocampus to perform voxelwise linear regressions. Lifetime cannabis consumption was assessed using the European School Survey Project on Alcohol and other Drugs (ESPAD), and PLEs were assessed with the Comprehensive Assessment Psychotic-like experiences (CAPE) tool. We first tested whether hippocampus/parahippocampus development was associated with PLEs. Then we formulated and tested an a priori simple mediation model in which uncus development mediates the association between lifetime cannabis consumption and PLEs.Results: We found that PLEs were associated with reduced expansion within a specific region of the right hippocampus/parahippocampus formation, the uncus (p = .002 at the cluster level, p = .018 at the peak level). The partial simple mediation model revealed a significant total effect from lifetime cannabis consumption to PLEs (b = 0.069, 95% CI = 0.04−0.1, p =2 × 10−16), as well as a small yet significant, indirect effect of right uncus development (0.004; 95% CI = 0.0004−0.01, p = .026).Conclusion: We show here that the uncus development is involved in the cerebral basis of PLEs in a population-based sample of healthy adolescents

Published
2020

8. Neural Correlates of Failed Inhibitory Control as an Early Marker of Disordered Eating in Adolescents

Author

Savani Bartholdy, Owen G. O’Daly, Iain C. Campbell, Tobias Banaschewski, Gareth Barker, Arun L.W. Bokde, Uli Bromberg, Christian Büchel, Erin Burke Quinlan, Sylvane Desrivières, Herta Flor, Vincent Frouin, Hugh Garavan, Penny Gowland, Andreas Heinz, Bernd Ittermann, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Frauke Nees, Dimitri Papadopoulos Orfanos, Luise Poustka, Sarah Hohmann, Juliane H. Fröhner, Michael N. Smolka, Henrik Walter, Robert Whelan, Gunter Schumann, Ulrike Schmidt, Michael Rapp, Eric Artiges, Sophia Schneider, Christine Bach, Tomas Paus, Alexis Barbot, null Gareth Barker, Arun Bokde, Nora Vetter, Anna Cattrell, Patrick Constant, Hans Crombag, Katharina Czech, Jeffrey Dalley, Benjamin Decideur, Tade Spranger, Tamzin Ripley, Nadja Heym, Wolfgang Sommer, Birgit Fuchs, Jürgen Gallinat, Rainer Spanagel, Mehri Kaviani, Bert Heinrichs, null Andreas Heinz, Naresh Subramaniam, Tianye Jia, Albrecht Ihlenfeld, James Ireland, Patricia Conrod, Jennifer Jones, Arno Klaassen, Christophe Lalanne, Dirk Lanzerath, Claire Lawrence, Hervé Lemaitre, Sylvane Desrivieres, Catherine Mallik, null Karl Mann, Adam Mar, Lourdes Martinez-Medina, null Jean-Luc Martinot, Eva Mennigen, Fabiana Mesquita de Carvahlo, Yannick Schwartz, Ruediger Bruehl, Kathrin Müller, Charlotte Nymberg, Mark Lathrop, null Trevor Robbins, Zdenka Pausova, null Jani Pentilla, Francesca Biondo, null Jean-Baptiste Poline, Sabina Millenet, null Michael Smolka, Juliane Fröhner, Maren Struve, null Steve Williams, Thomas Hübner, Semiha Aydin, John Rogers, Alexander Romanowski, Christine Schmäl, Dirk Schmidt, Stephan Ripke, Mercedes Arroyo, Florian Schubert, Yolanda Pena-Oliver, Mira Fauth-Bühler, Xavier Mignon, Claudia Speiser, Tahmine Fadai, null Dai Stephens, Andreas Ströhle, Marie-Laure Paillere, Nicole Strache, David Theobald, Sarah Jurk, Helene Vulser, Ruben Miranda, Juliana Yacubian, Alexander Genauck, Caroline Parchetka, Isabel Gemmeke, Johann Kruschwitz, Katharina Weiß, Jianfeng Feng, Dimitri Papadopoulos, Irina Filippi, Alex Ing, Barbara Ruggeri, Bing Xu, Christine Macare, Congying Chu, Eanna Hanratty, Gabriel Robert, Tao Yu, Veronika Ziesch, and Alicia Stedman

Subjects
0301 basic medicine, Male, medicine.medical_specialty, Adolescent, Binge eating, Prefrontal Cortex, Neuroimaging, Stop signal, Audiology, Gyrus Cinguli, Feeding and Eating Disorders, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Longitudinal Studies, Prospective Studies, Disordered eating, Prefrontal cortex, Inhibitory control, Biological Psychiatry, Anterior cingulate cortex, medicine.diagnostic_test, business.industry, Functional Neuroimaging, medicine.disease, Stop signal task, Magnetic Resonance Imaging, Eating disorders, Inhibition, Psychological, 030104 developmental biology, medicine.anatomical_structure, Case-Control Studies, Cohort, Female, medicine.symptom, Functional magnetic resonance imaging, business, 030217 neurology & neurosurgery, Biomarkers, Psychomotor Performance
Abstract

Background Binge eating and other forms of disordered eating behavior (DEB) are associated with failed inhibitory control. This study investigated the neural correlates of failed inhibitory control as a potential biomarker for DEB. Methods The study used prospective longitudinal data from the European IMAGEN study adolescent cohort. Participants completed baseline assessments (questionnaires and a brain scan [functional magnetic resonance imaging]) at 14 years of age and a follow-up assessment (questionnaires) at 16 years of age. Self-reported binge eating and/or purging were used to indicate presence of DEB. Neural correlates of failed inhibition were assessed using the stop signal task. Participants were categorized as healthy control subjects (reported no DEB at both time points), maintainers (reported DEB at both time points), recoverers (reported DEB at baseline only), and developers (reported DEB at follow-up only). Forty-three individuals per group with complete scanning data were matched on gender, age, puberty, and intelligence (N = 172). Results At baseline, despite similar task performance, incorrectly responding to stop signals (failed inhibitory control) was associated with greater recruitment of the medial prefrontal cortex and anterior cingulate cortex in the developers compared with healthy control subjects and recoverers. Conclusions Greater recruitment of the medial prefrontal and anterior cingulate regions during failed inhibition accords with abnormal evaluation of errors contributing to DEB development. As this precedes symptom onset and is evident despite normal task performance, neural responses during failed inhibition may be a useful biomarker of vulnerability for DEB. This study highlights the potential value of prospective neuroimaging studies for identifying markers of illness before the emergence of behavior changes.

Published
2019
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9. Population model analysis of chiral inversion and degradation of bupropion enantiomers, and application to enantiomer specific fraction unbound determination in rat plasma and brain

Author

Chandrali Bhattacharya, Robert E. Stratford, Christine Bach, and Andrea R. Masters

Subjects
Bioanalysis, Clinical Biochemistry, Kinetics, Pharmaceutical Science, Plasma protein binding, 01 natural sciences, Article, Analytical Chemistry, Drug Discovery, medicine, Pharmacologic effects, Animals, Bupropion, Spectroscopy, Chromatography, 010405 organic chemistry, Chemistry, 010401 analytical chemistry, Brain, Stereoisomerism, Plasma, Receptor–ligand kinetics, Rats, 0104 chemical sciences, Pharmaceutical Preparations, Enantiomer, medicine.drug
Abstract

Pharmacologic effects elicited by drugs most directly relate to their unbound concentrations. Measurement of binding in blood, plasma and target tissues are used to estimate these concentrations by determining the fraction of total concentration in a biological matrix that is not bound. In the case of attempting to estimate R- and S-bupropion concentrations in plasma and brain following racemic bupropion administration, reversible chiral inversion and irreversible degradation of the enantiomers were hypothesized to confound attempts at unbound fraction estimation. To address this possibility, a kinetic modeling approach was used to quantify inversion and degradation specific processes for each enantiomer from separate incubations of each enantiomer in the two matrices, and in pH 7.4 buffer, which is also used in binding experiments based on equilibrium dialysis. Modeling analyses indicated that chiral inversion kinetics were two to four-fold faster in plasma and brain than degradation, with only inversion observed in buffer. Inversion rate was faster for S-bupropion in the three media; whereas, degradation rates were similar for the two enantiomers in plasma and brain, with overall degradation in plasma approximately 2-fold higher than in brain homogenate. Incorporation of degradation and chiral inversion kinetic terms into a model to predict enantiomer-specific binding in plasma and brain revealed that, despite existence of these two processes, empirically derived estimates of fraction unbound were similar to model-derived values, leading to a firm conclusion that observed extent of plasma and brain binding are accurate largely because binding kinetics are faster than parallel degradation and chiral inversion processes.

Published
2021

12. Bürgersinn und Unternehmergeist : Stifter und Stiftungen in Hamburg nach 1945

Author

Christine Bach and Christine Bach

Subjects
Entrepreneurship--Social aspects--History.--, Middle class--History.--Germany--Hamburg, Charitable uses, trusts, and foundations--Histor, Social responsibility of business--History.--G, Industries--Social aspects--History.--German
Abstract

Seit Jahrhunderten zählen die Errichtung von Stiftungen und die Ausübung karitativer Ehrenamtlichkeit zu den zentralen Ausdrucksformen Hamburger Bürger. Nach dem Niedergang des traditionsreichen Hamburger Stiftungssektors durch Krieg, Inflation und die Gewaltherrschaft der Nationalsozialisten kam es in der zweiten Hälfte des 20. Jahrhunderts zu einem deutlichen Wiederaufschwung.Die Autorin untersucht die Gründe für diese Entwicklung und benennt als zentrale Faktoren den Fortbestand und die Weiterentwicklung von Traditionen bürgerlichen Gemeinsinns, die stiftungs-freundliche politische Kultur der Hansestadt und den ökonomischen Erfolg einzelner Unternehmer in der Nachkriegszeit. Vor dem Hintergrund der Sozial- und Kulturgeschichte Hamburgs leistet die Studie einen Beitrag zur bislang wenig erforschten Geschichte des Bürgertums nach 1945.

Published
2014

13. Subthreshold Depression and Regional Brain Volumes in Young Community Adolescents

Author

Robert Goodman, D. Hall, Naresh Subramaniam, Z. Bricaud, Marcella Rietschel, Tomáš Paus, S. Nugent, Tahmine Fadai, Robert Whelan, Jani Penttilä, Hélène Vulser, J-B Poline, Trevor W. Robbins, Michael A. Rapp, Amir M. Tahmasebi, Kathrin U. Müller, John M. Rogers, L. Smith, L. Topper, Bernadeta Walaszek, Gunter Schumann, Sabina Millenet, Dai Stephens, Tianye Jia, Nicole Strache, Nora C. Vetter, Bernd Ittermann, Andreas Heinz, Sophia Schneider, James Ireland, Nadja Heym, Colm G. Connolly, James V. Jones, Marie Laure Paillère-Martinot, Stephan Ripke, Andreas Ströhle, Zdenka Pausova, Herve Lemaitre, Laurence J. Reed, Tobias Banaschewski, S. Havatzias, Barbara Ruggeri, Jessica Massicotte, Viola Kappel, Albrecht Ihlenfeld, Claire Lawrence, Karl Mann, Eric Artiges, C. Andrew, K. Stueber, Hugh Garavan, Sylvane Desrivières, Irina Filippi, Thomas Hübner, André Galinowski, Frauke Nees, Penny A. Gowland, Rüdiger Brühl, Maren Struve, Arun L.W. Bokde, Fanny Gollier-Briant, Nadege Bordas, C. Newman, Argyris Stringaris, Jeffrey W. Dalley, Patricia J. Conrod, Catherine Mallik, Vincent Frouin, D. Carter, C. Nymberg, David E. H. Theobald, Jean-Luc Martinot, Eva Loth, Jan Reuter, Christine Bach, Gareth J. Barker, Rainer Spanagel, Mira Fauth-Bühler, Mark Lathrop, Uli Bromberg, Eva Mennigen, Luise Poustka, Christian Büchel, Ruben Miranda, Anna Cattrell, Christophe Lalanne, Benjamin Thyreau, L. Albrecht, Juliana Yacubian, Dirk Schmidt, Yannick Schwartz, Nikolay Ivanov, Yvonne Grimmer, Michael N. Smolka, Herta Flor, Juergen Gallinat, Sarah Rodehacke, Kay Head, H. Werts, and Veronika Ziesch

Subjects
Male, Adolescent, Neuroimaging, Gyrus Cinguli, Brain mapping, Article, White matter, Developmental and Educational Psychology, medicine, Humans, Gray Matter, Child, Psychiatric Status Rating Scales, Brain Mapping, medicine.diagnostic_test, Depression, Subthreshold conduction, Mental Disorders, Case-control study, Brain, Magnetic resonance imaging, Organ Size, medicine.disease, Magnetic Resonance Imaging, White Matter, Frontal Lobe, Europe, Psychiatry and Mental health, Logistic Models, medicine.anatomical_structure, Frontal lobe, Case-Control Studies, Major depressive disorder, Female, Psychology, Clinical psychology
Abstract

Objective Neuroimaging findings have been reported in regions of the brain associated with emotion in both adults and adolescents with depression, but few studies have investigated whether such brain alterations can be detected in adolescents with subthreshold depression, a condition at risk for major depressive disorder. In this study, we searched for differences in brain structure at age 14 years in adolescents with subthreshold depression and their relation to depression at age 16 years. Method High-resolution structural magnetic resonance imaging was used to assess adolescents with self-reported subthreshold depression (n = 119) and healthy control adolescents (n = 461), all recruited from a community-based sample. Regional gray and white matter volumes were compared across groups using whole-brain voxel-based morphometry. The relationship between subthreshold depression at baseline and depression outcome was explored using causal mediation analyses to search for mediating effects of regional brain volumes. Results Adolescents with subthreshold depression had smaller gray matter volume in the ventromedial prefrontal and rostral anterior cingulate cortices and caudates, and smaller white matter volumes in the anterior limb of internal capsules, left forceps minor, and right cingulum. In girls, but not in boys, the relation between subthreshold depression at baseline and high depression score at follow-up was mediated by medial–prefrontal gray matter volume. Conclusion Subthreshold depression in early adolescence might be associated with smaller gray and white matter volumes in regions of the frontal–striatal–limbic affective circuit, and the occurrence of depression in girls with subthreshold depression might be influenced by medial–prefrontal gray matter volume. However, these findings should be interpreted with caution because of the limitations of the clinical assessment methods.

Published
2015

14. Field evaluation of the diagnostic performance of EasyScan GO: a digital malaria microscopy device based on machine-learning

Author

Debashish Das, Ranitha Vongpromek, Thanawat Assawariyathipat, Ketsanee Srinamon, Kalynn Kennon, Kasia Stepniewska, Aniruddha Ghose, Abdullah Abu Sayeed, M. Abul Faiz, Rebeca Linhares Abreu Netto, Andre Siqueira, Serge R. Yerbanga, Jean Bosco Ouédraogo, James J. Callery, Thomas J. Peto, Rupam Tripura, Felix Koukouikila-Koussounda, Francine Ntoumi, John Michael Ong’echa, Bernhards Ogutu, Prakash Ghimire, Jutta Marfurt, Benedikt Ley, Amadou Seck, Magatte Ndiaye, Bhavani Moodley, Lisa Ming Sun, Laypaw Archasuksan, Stephane Proux, Sam L. Nsobya, Philip J. Rosenthal, Matthew P. Horning, Shawn K. McGuire, Courosh Mehanian, Stephen Burkot, Charles B. Delahunt, Christine Bachman, Ric N. Price, Arjen M. Dondorp, François Chappuis, Philippe J. Guérin, and Mehul Dhorda

Subjects
Malaria, Light microscopy, Digital microscopy, Artificial intelligence, Diagnostic accuracy, Machine-learning, Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Microscopic examination of Giemsa-stained blood films remains the reference standard for malaria parasite detection and quantification, but is undermined by difficulties in ensuring high-quality manual reading and inter-reader reliability. Automated parasite detection and quantification may address this issue. Methods A multi-centre, observational study was conducted during 2018 and 2019 at 11 sites to assess the performance of the EasyScan Go, a microscopy device employing machine-learning-based image analysis. Sensitivity, specificity, accuracy of species detection and parasite density estimation were assessed with expert microscopy as the reference. Intra- and inter-device reliability of the device was also evaluated by comparing results from repeat reads on the same and two different devices. This study has been reported in accordance with the Standards for Reporting Diagnostic accuracy studies (STARD) checklist. Results In total, 2250 Giemsa-stained blood films were prepared and read independently by expert microscopists and the EasyScan Go device. The diagnostic sensitivity of EasyScan Go was 91.1% (95% CI 88.9–92.7), and specificity 75.6% (95% CI 73.1–78.0). With good quality slides sensitivity was similar (89.1%, 95%CI 86.2–91.5), but specificity increased to 85.1% (95%CI 82.6–87.4). Sensitivity increased with parasitaemia rising from 57% at 200–200,000 parasite/µL. Species were identified accurately in 93% of Plasmodium falciparum samples (kappa = 0.76, 95% CI 0.69–0.83), and in 92% of Plasmodium vivax samples (kappa = 0.73, 95% CI 0.66–0.80). Parasite density estimates by the EasyScan Go were within ± 25% of the microscopic reference counts in 23% of slides. Conclusions The performance of the EasyScan Go in parasite detection and species identification accuracy fulfil WHO-TDR Research Malaria Microscopy competence level 2 criteria. In terms of parasite quantification and false positive rate, it meets the level 4 WHO-TDR Research Malaria Microscopy criteria. All performance parameters were significantly affected by slide quality. Further software improvement is required to improve sensitivity at low parasitaemia and parasite density estimations. Trial registration ClinicalTrials.gov number NCT03512678.

Published
2022
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16. Collaborateurs

Author

Sébastien Albert, Dominique Allais, Ihab Atallah, Karine Aubry, Emmanuel Babin, Christine Bach, Bertrand Baujat, David Blanchard, Alexandre Bozec, Le Moal Laurence Bozec, Daniel Brasnu, Philippe Céruse, Frédéric Chabolle, Benoist Chibaudel, Alain Cosmidis, Florence Cuny, Cédric d'Hauthuille, Stéphanie Dakpé, Olivier Dassonville, Sarah Dauchy, Julien Davrou, Dominique de Raucourt, Bernard Devauchelle, Gilles Dolivet, Clément Dumont, Marie-Noëlle Falewee, Renaud Garrel, Marie Gavid, Ève Gelsi, Philippe Giraud, Joël Guigay, Guillaume Grandazzi, Karim Hammoudi, Stéphane Hans, Christophe Hebert, Natacha Heutte, Martin Housset, Sébastien Jaffré, Franck Jégoux, Laurent Laccourreye, Ollivier Laccourreye, Marc Makeieff, Olivier Malard, Sylvain Moriniere, Geoffrey Mortuaire, Malou Navez, Stéphane Oudard, Nicole Pelicier, Bérengère Phulpin, Laetitia Plisson, Jean-Michel Prades, Virginie Prévost, Michèle Puech, Christine Rebiere, Michel Reich, Émile Reyt, Christian-Adrien Righini, Philippe Schultz, Florian Scotte, Sylvie Testelin, Juliette Thariat, Andreï Timochenko, Sébastien Vergez, and Virginie Woisard

Published
2013

17. Cultured allogenic keratinocytes for extensive burns: a retrospective study over 15 years

Author

Pierre Lacroix, Hristo Shipkov, Christine Bach, Zulma Catherine, Céline Auxenfans, Odile Damour, Fabienne Braye, and Marc Bertin-Maghit

Subjects
Adult, Keratinocytes, Male, medicine.medical_specialty, Adolescent, Cell Transplantation, Treatment outcome, Cell Culture Techniques, Critical Care and Intensive Care Medicine, Severity of Illness Index, Transplant Donor Site, Cohort Studies, Young Adult, Cell transplantation, Severity of illness, medicine, Humans, Transplantation, Homologous, Child, Cells, Cultured, Aged, Retrospective Studies, Aged, 80 and over, Wound Healing, business.industry, Baux score, Infant, Retrospective cohort study, General Medicine, Skin Transplantation, Middle Aged, Skin transplantation, Surgery, Treatment Outcome, Child, Preschool, Emergency Medicine, Female, business, Burns, Cohort study
Abstract

The aim was to review the use and indications of cultured allogenic keratinocytes (CAlloK) in extensive burns and their efficiency. Materials and methods This retrospective study comprised 15 years (1997–2012). Inclusion criteria: all patients who received CAlloK. Exclusion criteria: patients who died before complete healing. Evaluation criteria were clinical. Time and success of wound healing after CAlloK use were evaluated. Results The CAlloK were used for 2 indications – STSG donor sites and deep 2nd degree burns in extensively burned patients. A total of 70 patients were included with severity Baux score of 99.2 (from 51 to 144) and mean percentage of TBSA of 63.49% (from 21 to 96%). Fifty nine patients received CAlloK for STSG donor sites with a mean number of applications of 4 and mean surface of 3800 cm2 per patient. Treated donor sites were re-harvested 2.5 times. The mean time of complete epithelialization was 7 days. In 11 patients, CAlloK were used for deep 2nd degree burns. The mean percentage of burned surface was 73.7%. The mean surface of CAlloK per patient was 2545 cm2. Complete healing was achieved in 6.4 days. Conclusion The CAlloK allow rapid healing of STSG donor-sites and deep 2nd second degree burns in extensively burned patients.

Published
2012

18. Chirurgie plastique réparatrice de la face et du cou - Volume 1

Author

Jean-Pierre Bessède, Jean-Paul Adenis, Sébastien Albert, Christine Bach, Bertrand Baujat, Claude Beauvillain de Montreuil, Philippe Boudard, Jean-Baptiste Charrier, Vincent Darsonval, Françoise Dehesdin, Françoise Desnoyelles, François Disant, Peggy Gatignol, Alain Jourdain, Darina Krastinova, Daniel Labbé, Georges Lamas, Olivier Malard, Pierre-Yves Robert, Yves Saban, Jean-Philippe Sannajust, Frédéric Tankere, Vincent Darrouzet, Charles Guedon, Seli ARSLAN, Jean-Pierre Bessède, Jean-Paul Adenis, Sébastien Albert, Christine Bach, Bertrand Baujat, Claude Beauvillain de Montreuil, Philippe Boudard, Jean-Baptiste Charrier, Vincent Darsonval, Françoise Dehesdin, Françoise Desnoyelles, François Disant, Peggy Gatignol, Alain Jourdain, Darina Krastinova, Daniel Labbé, Georges Lamas, Olivier Malard, Pierre-Yves Robert, Yves Saban, Jean-Philippe Sannajust, Frédéric Tankere, Vincent Darrouzet, Charles Guedon, and Seli ARSLAN

Subjects
Neck--Surgery, Surgery, Plastic, Face--Surgery
Abstract

La chirurgie plastique et réparatrice de visage doit être abordée dans sa globalité. Ce premier volume, pratique et didactique, reprend les différentes techniques utilisées en chirurgie plastique et réparatrice de la face et du cou. Il traite des plaies du visage, de la traumatologie faciale, de la cicatrisation et des pansements. Il détaille les principes et les techniques de réparation des pertes de substance. Les différentes réparations topographiques sont présentées à l'aide d'une iconographie riche : dessins, cas cliniques et vidéos opératoires en ligne. Enfin, la dernière partie de l'ouvrage est consacrée au versant fonctionnel en traitant de la prise en charge des séquelles des paralysies faciales. Fruit de la longue expérience clinique des auteurs, les techniques présentées ici doivent permettent aux chirurgiens chevronnés et à ceux en cours de formation de faire face à de nombreuses situations cliniques. Pour accéder au complément en ligne de cet ouvrage, cliquez ici.Les différentes techniques utilisées en chirurgie plastique et réparatrice de la face et du cou - Les plaies du visage. - La traumatologie faciale. - La cicatrisation. - Les pansements. - Les principes et les techniques de réparation des pertes de substance. - Les différentes réparations topographiques illustrées par des dessins et des cas cliniques. - La prise en charge des séquelles des paralysies faciales. (Logo compléments en ligne) Avec cet ouvrage : des vidéos opératoires accessibles via un code privatif.

Published
2011

20. A feasibility study evaluating a reservoir storage system for continuous oxygen delivery for children with hypoxemia in Kenya

Author

Dickson Otiangala, Nicholas O. Agai, Bernard Olayo, Steve Adudans, Chin Hei Ng, Ryan Calderon, Ella Forgie, Christine Bachman, Daniel Lieberman, David Bell, Michael Hawkes, and Akos Somoskovi

Subjects
Pneumonia, Hypoxemia, Electricity, Global health, Africa, Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Supplemental oxygen is an essential treatment for childhood pneumonia but is often unavailable in low-resource settings or unreliable due to frequent and long-lasting power outages. We present a novel medium pressure reservoir (MPR) which delivers continuous oxygen to pediatric patients through power outages. Methods An observational case series pilot study assessing the capacity, efficacy and user appraisal of a novel MPR device for use in low-resource pediatric wards. We designed and tested a MPR in a controlled preclinical setting, established feasibility of the device in two rural Kenyan hospitals, and sought user feedback and satisfaction using a standardized questionnaire. Results Preclinical data showed that the MPR was capable of bridging power outages and delivering a continuous flow of oxygen to a simulated patient. The MPR was then deployed for clinical testing in nine pediatric patients at Ahero and Suba Hospitals. Power was unavailable for 2% of the total time observed due to 11 power outages (median 4.6 min, IQR 3.6–13.0 min) that occurred during treatment with the MPR. Oxygen flowrates remained constant across all 11 power outages. Feedback on the MPR was uniformly positive; all respondents indicated that the MPR was easy to use and provided clinically significant help to their patients. Conclusion We present a MPR oxygen delivery device that has the potential to mitigate power insecurity and improve the standard of care for hypoxemic pediatric patients in resource-limited settings.

Published
2021
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21. Storming the castle: A case report of multi‐system dysregulation in a child with Castleman disease

Author

Samantha J. DeMarsh, Nicole E. Kendel, Christine Bacha, Stacy P. Ardoin, Samir Kahwash, and Melissa J. Rose

Subjects
angiofollicular, Castleman, hyperplasia, interleukin‐6, lymphoproliferative, Medicine, Medicine (General), R5-920
Abstract

Abstract Castleman disease is a non‐clonal, lymphoproliferative disorder rarely seen in children. Presented is a 12‐year‐old male with progressive abdominal pain, vomiting, and fever. Diagnostic testing revealed multi‐organ system involvement and the diagnosis was ultimately made with tissue biopsy. Marked disease regression occurred after high‐dose steroids and continued interleukin‐6 inhibition.

Published
2022
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29. Field evaluation of a prototype tuberculosis lipoarabinomannan lateral flow assay on HIV-positive and HIV-negative patients.

Author

John T Connelly, Alfred Andama, Benjamin D Grant, Alexey Ball, Sandra Mwebe, Lucy Asege, Martha Nakaye, Brianda Barrios Lopez, Helen V Hsieh, David Katumba, Job Mukwatamundu, Mayimuna Nalubega, Victoria M Hunt, Stephen Burkot, Harisha Ramachandraiah, Alok Choudhary, Lech Ignatowicz, Bernhard H Weigl, Christine Bachman, Jerry Mulondo, Fred Semitala, William Worodria, Abraham Pinter, Beston Hamasur, David Bell, Adithya Cattamanchi, and Akos Somoskovi

Subjects
Medicine, Science
Abstract

Detection of tuberculosis at the point-of-care (POC) is limited by the low sensitivity of current commercially available tests. We describe a diagnostic accuracy field evaluation of a prototype urine Tuberculosis Lipoarabinomannan Lateral Flow Assay (TB-LAM LFA) in both HIV-positive and HIV-negative patients using fresh samples with sensitivity and specificity as the measures of accuracy. This prototype combines a proprietary concentration system with a sensitive LFA. In a prospective study of 292 patients with suspected pulmonary tuberculosis in Uganda, the clinical sensitivity and specificity was compared against a microbiological reference standard including sputum Xpert MTB/RIF Ultra and solid and liquid culture. TB-LAM LFA had an overall sensitivity of 60% (95%CI 51-69%) and specificity of 80% (95%CI 73-85%). When comparing HIV-positive (N = 86) and HIV-negative (N = 206) patients, there was no significant difference in sensitivity (sensitivity difference 8%, 95%CI -11% to +24%, p = 0.4351) or specificity (specificity difference -9%, 95%CI -24% to +4%, p = 0.2051). Compared to the commercially available Alere Determine TB-LAM Ag test, the TB-LAM LFA prototype had improved sensitivity in both HIV-negative (difference 49%, 95%CI 37% to 59%, p200cells/μL (difference 59%, 95%CI 32% to 75%, p = 0.0009). This report is the first to show improved performance of a urine TB LAM test for HIV-negative patients in a high TB burden setting. We also offer potential assay refinement solutions that may further improve sensitivity and specificity.

Published
2021
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30. Establishment of a Plasmid-Based Reverse Genetics System for the Cell Culture-Adapted Hepatitis E Virus Genotype 3c Strain 47832c

Author

Johannes Scholz, Christine Bächlein, Ashish K. Gadicherla, Alexander Falkenhagen, Simon H. Tausch, and Reimar Johne

Subjects
hepatitis e virus, genotype 3c, cell culture, reverse genetics system, site-directed mutagenesis, Medicine
Abstract

The hepatitis E virus (HEV) causes acute and chronic hepatitis in humans. Investigation of HEV replication is hampered by the lack of broadly applicable, efficient cell culture systems and tools for site-directed mutagenesis of HEV. The cell culture-adapted genotype 3c strain 47832c, which represents a typical genotype predominantly detected in Europe, has previously been used for several basic and applied research studies. Here, a plasmid-based reverse genetics system was developed for this strain, which efficiently rescued the infectious virus without the need for in vitro RNA transcription. The cotransfection of T7 RNA polymerase-expressing BSR/T7 cells with one plasmid encoding the full-length viral genome and two helper plasmids encoding vaccinia virus capping enzymes resulted in the production of infectious HEV, which could be serially passaged on A549/D3 cells. The parental and recombinant virus exhibited similar replication kinetics. A single point mutation creating an additional restriction enzyme site could be successfully introduced into the virus genome of progeny virus, indicating that the system is suitable for site-directed mutagenesis. This system is the first plasmid-based HEV reverse genetics system, as well as the first reverse genetics system for HEV genotype 3c, and should therefore be of broad use for basic and applied HEV research.

Published
2020
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31. Real-Time Prediction of Observed Action Requires Integrity of the Dorsal Premotor Cortex: Evidence From Repetitive Transcranial Magnetic Stimulation

Author

Louisa F. M. Brich, Christine Bächle, Joachim Hermsdörfer, and Waltraud Stadler

Subjects
action observation, prediction, premotor cortex, simulation, TMS, rTMS, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Studying brain mechanisms underlying the prediction of observed action, the dorsal premotor cortex (PMd) has been suggested a key area. The present study probed this notion using repetitive transcranial magnetic stimulation (rTMS) to test whether interference in this area would affect the accuracy in predicting the time course of object directed actions performed with the right hand. Young and healthy participants observed actions in short videos. These were briefly occluded from view for 600 ms and resumed immediately afterwards. The task was to continue the action mentally and to indicate after each occlusion, whether the action was resumed at the right moment (condition in-time) or shifted. In a first run, single-pulse transcranial magnetic stimulation (sTMS) was delivered over the left primary hand-area during occlusion. In the second run, rTMS over the left PMd was applied during occlusion in half of the participants [experimental group (EG)]. The control group (CG) received sham-rTMS over the same area. Under rTMS, the EG predicted less trials correctly than in the sTMS run. Sham-rTMS in the CG had no effects on prediction. The interference in PMd interacted with the type of manipulation applied to the action’s time course occasionally during occlusion. The performance decrease of the EG was most pronounced in conditions in which the continuations after occlusions were too late in the action’s course. The present results extend earlier findings suggesting that real-time action prediction requires the integrity of the PMd. Different functional roles of this area are discussed. Alternative interpretations consider either simulation of specific motor programming functions or the involvement of a feature-unspecific predictor.

Published
2018
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32. Designing student learning outcomes in undergraduate architecture education: Frameworks for assessment

Author

Leonard R. Bachman and Christine Bachman

Subjects
Architecture, NA1-9428
Abstract

On the cusp of transition to the National Architectural Accrediting Board (NAAB) 2009 Conditions for Accreditation, and at the juncture of higher education’s transition into a culture of assessment, this paper addressesthe rationale and frameworks for the design of student learningobjectives. The circumstances of undergraduate architectural education are the primary target here, but the same principles will apply to graduatelearning as well. The discussion is itself framed by a comparison to aset of model student learning objectives published by the American Psychology Association, and is structured within the conventionalplanning model of mission, values, goals, objectives, tactics, and strategies. For the purpose of discussion, the authors propose severalhypothetical examples.

Published
2009
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33. Affecting Change in Architectural Education

Author

Leonard R. Bachman and Christine Bachman

Subjects
Architecture, NA1-9428
Abstract

Architecture concerns not so much an explicit body of transmittable knowledge and protocols as it does a set of implicit understandings, sensitivities and sensibilities. The education of an architect therefore concerns the mission of endowing candidates with those implicit traits. This is not to say that architects do not possess and wield prodigious amounts of explicit cognitive knowledge, because they certainly do. But that explicit component of architectural know-how is actually vested in and deployed by the architect not so much because the knowledge has been invented, discovered, or developed by architects; but rather because they have assimilated it from other disciplines in a special way that gives architects adductive and hermeneutic insight into vast, detailed, and complex design challenges. Engineers make better machines, artists make more meaningful artifacts, and psychologists provide better human environments; but architects are trained to see the underlying opportunity and potential celebration of how those constituent menus might become a feast. In any unresolved complex of space, material and form, architects grasp a unique essence in how they perceive the “happily ever after” of what it might be and how that vision might be made whole and concrete. By the time a student of architecture is fully indoctrinated, this grasp of an underlying ideal essence is so potent that it becomes the student’s identity… and the purpose of that insight becomes an irresistible intention.

Published
2009
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