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1. Autonomous detection of high-voltage towers employing unmanned aerial vehicles

Author

Universitat Politècnica de Catalunya. Departament d'Arquitectura de Computadors, Valero García, Miguel, Colomé Sanz, Ferran, Universitat Politècnica de Catalunya. Departament d'Arquitectura de Computadors, Valero García, Miguel, and Colomé Sanz, Ferran

Abstract

Monitoring and controlling the power grid is extremely important to prevent power outages and blackouts. Traditionally, the most common methods for inspecting high-voltage towers and power lines include visual inspections by qualified personnel, inspections by helicopters, and, in some cases, the use of specialized robots, among others. These inspections aim to detect anomalies near the infrastructure, anomalies due to hotspots in the insulation or visual defects in the various structural elements. One of the main problems of these techniques is the high economic cost and the lack of accuracy. As an alternative, unmanned aerial vehicles (UAVs) are becoming more popular in the market, and the trend is gradually moving towards this technology, as it offers significant cost reduction, better mobility and flexibility, and great potential for obtaining high-quality images. This thesis (TFG) studies the feasibility of developing a system capable of autonomously detecting high-voltage towers using an unmanned aerial vehicle and conducting power line inspections. This system consists of a desktop application that allows the user to program legs of a flight plan, and a drone that executes them and detects the high-voltage towers using an artificial intelligence model. The system developed in this study is part of a contribution to the Drone Engineering Ecosystem (DEE), a platform for controlling and monitoring unmanned aerial vehicles using desktop and/or web applications. The main goal of this platform is the improvement and continuity of its development by future students., Objectius de Desenvolupament Sostenible::9 - Indústria, Innovació i Infraestructura

Published
2023

2. eTRANSAFE:data science to empower translational safety assessment

Author

Sanz, Ferran, Pognan, François, Steger-Hartmann, Thomas, Díaz, Carlos, Asakura, Shoji, Amberg, Alexander, Bécourt-Lhote, Nathalie, Blomberg, Niklas, Bosc, Nicolas, Briggs, Katharine, Bringezu, Frank, Brulle-Wohlhueter, Claire, Brunak, Søren, Bueters, Ruud, Callegaro, Giulia, Capella-Gutierrez, Salvador, Centeno, Emilio, Corvi, Javier, Cronin, Mark T.D., Drew, Philip, Duchateau-Nguyen, Guillemette, Ecker, Gerhard F., Escher, Sylvia, Felix, Eloy, Ferreiro, Miguel, Frericks, Markus, Furlong, Laura I., Geiger, Robert, George, Catherine, Grandits, Melanie, Ivanov-Draganov, Dragomir, Kilgour-Christie, Jean, Kiziloren, Tevfik, Kors, Jan A., Koyama, Naoki, Kreuchwig, Annika, Leach, Andrew R., Mayer, Miguel Angel, Monecke, Peter, Muster, Wolfgang, Nakazawa, Chihiro Miyamoto, Nicholson, Gavin, Parry, Rowan, Pastor, Manuel, Piñero, Janet, Oberhauser, Nils, Ramírez-Anguita, Juan Manuel, Rodrigo, Adrián, Smajic, Aljosa, Schaefer, Markus, Schieferdecker, Sebastian, Soininen, Inari, Terricabras, Emma, Trairatphisan, Panuwat, Turner, Sean C., Valencia, Alfonso, van de Water, Bob, van der Lei, Johan L., van Mulligen, Erik M., Vock, Esther, Wilkinson, David, Sanz, Ferran, Pognan, François, Steger-Hartmann, Thomas, Díaz, Carlos, Asakura, Shoji, Amberg, Alexander, Bécourt-Lhote, Nathalie, Blomberg, Niklas, Bosc, Nicolas, Briggs, Katharine, Bringezu, Frank, Brulle-Wohlhueter, Claire, Brunak, Søren, Bueters, Ruud, Callegaro, Giulia, Capella-Gutierrez, Salvador, Centeno, Emilio, Corvi, Javier, Cronin, Mark T.D., Drew, Philip, Duchateau-Nguyen, Guillemette, Ecker, Gerhard F., Escher, Sylvia, Felix, Eloy, Ferreiro, Miguel, Frericks, Markus, Furlong, Laura I., Geiger, Robert, George, Catherine, Grandits, Melanie, Ivanov-Draganov, Dragomir, Kilgour-Christie, Jean, Kiziloren, Tevfik, Kors, Jan A., Koyama, Naoki, Kreuchwig, Annika, Leach, Andrew R., Mayer, Miguel Angel, Monecke, Peter, Muster, Wolfgang, Nakazawa, Chihiro Miyamoto, Nicholson, Gavin, Parry, Rowan, Pastor, Manuel, Piñero, Janet, Oberhauser, Nils, Ramírez-Anguita, Juan Manuel, Rodrigo, Adrián, Smajic, Aljosa, Schaefer, Markus, Schieferdecker, Sebastian, Soininen, Inari, Terricabras, Emma, Trairatphisan, Panuwat, Turner, Sean C., Valencia, Alfonso, van de Water, Bob, van der Lei, Johan L., van Mulligen, Erik M., Vock, Esther, and Wilkinson, David

Published
2023

3. Estudi sobre l'aplicabilitat de piezoelèctrics com a sensors per a la previsió del dany en impacte

Author

Universitat Politècnica de Catalunya. Departament de Resistència de Materials i Estructures a l'Enginyeria, Universitat Politècnica de Catalunya. Departament d'Enginyeria Electrònica, Bernat Masó, Ernest, Ferrer Arnau, Luis Jorge, Urquía Sanz, Ferran, Universitat Politècnica de Catalunya. Departament de Resistència de Materials i Estructures a l'Enginyeria, Universitat Politècnica de Catalunya. Departament d'Enginyeria Electrònica, Bernat Masó, Ernest, Ferrer Arnau, Luis Jorge, and Urquía Sanz, Ferran

Abstract

En aquest treball, s'estudiarà el comportament de dispositius piezoelèctrics davant esdeveniments d'impacte, amb la finalitat d'utilitzar-los com a sensors per preveure el dany ocasionat en un substrat determinat per única causa de l'impacte. Per fer-ho, es dissenyarà el pertinent circuit elèctric capaç de generar un senyal a partir de la resposta piezoelèctrica, i s'establirà un procediment de lectura d'aquest mitjançant un dispositiu, en aquest cas, un microcontrolador. A més es dissenyarà una configuració d'assaig i una matriu d'assajos, on sotmetent els sensors a impactes en un substrat determinat, es buscarà esclarir el comportament dels sensors envers diverses condicions d'impacte tenint en compte diferents variables com l'energia d'impacte o la velocitat d'impacte entre d'altres. Amb la informació provinent dels resultats dels assajos, i mitjançant raonaments científics es faran afirmacions i hipòtesis sobre el comportament dels sensors i es raonarà la viabilitat d'aplicar-los com a sensors per a la previsió del dany en impacte. Finalment i si escau, es proposaran noves vies per continuar la investigació amb la finalitat de confirmar o desmentir les afirmacions i hipòtesis mencionades en aquest treball., This project will study the behavior of piezoelectric devices against impact events, with the purpose of using them as sensors to foresee the damage caused in a certain substrate by only cause of the impact on itself. To do that, the corresponding electric circuit will be designed to generate an electric signal based on the piezoelectric response. After that, a procedure for reading this measurement through an external device will be established, concretely for the case of this project we will use a microcontroller. Besides that, the corresponding test method and test matrix will be designed, in which the sensors will be submitted to impact events placed in a specific substrate. We will try to clarify the behavior of piezoelectric sensors by exposing the substrate to different impact conditions, using diverse variables such as impact energy or impact speed among others. Using the information provided by the testing results, and through scientific reasoning, statements and hypothesis will be made related to sensor's behavior, and we will discuss the viability of applying them as impact damage sensors. Finally, and if applicable, new investigation lines will be purposed to continue the investigation with the intention of confirming or denying the already mentioned statements and hypothesis.

Published
2022

4. The eTRANSAFE project on translational safety assessment through integrative knowledge management: achievements and perspectives

Author

Barcelona Supercomputing Center, Pognan, François, Steger-Hartmann, Thomas, Díaz, Carlos, Blomberg, Niklas, Bringezu, Frank, Briggs, Katharine, Callegaro, Giulia, Capella Gutiérrez, Salvador, Centeno, Emilio, Corvi, Javier, Drew, Philip, Drewe, William C., Fernández González, Jose María, Furlong, Laura I., Guney, Emre, Kors, Jan A., Mayer, Miguel Angel, Pastor, Manuel, Piñero, Janet, Ramírez-Anguita, Juan Manuel, Ronzano, Francesco, Rowell, Philip, Saüch-Pitarch, Josep, Valencia, Alfonso, Water, Bob van de, Lei, Johan van der, Mulligen, Erik van, Sanz, Ferran, Barcelona Supercomputing Center, Pognan, François, Steger-Hartmann, Thomas, Díaz, Carlos, Blomberg, Niklas, Bringezu, Frank, Briggs, Katharine, Callegaro, Giulia, Capella Gutiérrez, Salvador, Centeno, Emilio, Corvi, Javier, Drew, Philip, Drewe, William C., Fernández González, Jose María, Furlong, Laura I., Guney, Emre, Kors, Jan A., Mayer, Miguel Angel, Pastor, Manuel, Piñero, Janet, Ramírez-Anguita, Juan Manuel, Ronzano, Francesco, Rowell, Philip, Saüch-Pitarch, Josep, Valencia, Alfonso, Water, Bob van de, Lei, Johan van der, Mulligen, Erik van, and Sanz, Ferran

Abstract

eTRANSAFE is a research project funded within the Innovative Medicines Initiative (IMI), which aims at developing integrated databases and computational tools (the eTRANSAFE ToxHub) that support the translational safety assessment of new drugs by using legacy data provided by the pharmaceutical companies that participate in the project. The project objectives include the development of databases containing preclinical and clinical data, computational systems for translational analysis including tools for data query, analysis and visualization, as well as computational models to explain and predict drug safety events., This research received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreements eTRANSAFE (777365). This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA companies in kind contribution. The Research Programme on Biomedical Informatics (GRIB) of IMIM and DCEXS-UPF is a member of the Spanish National Bioinformatics Institute (INB), PRB2-ISCIII and is supported by grant PT13/0001/0023, of the PE I + D + i 2013–2016, funded by ISCIII and FEDER. The GRIB also receive support from Agència de Gestió D’ajuts Universitaris i de Recerca Generalitat de Catalunya (AGAUR, ref.: 2017SGR01020). The DCEXS is a “Unidad de Excelencia María de Maeztu”, funded by the MINECO (ref: MDM-2014-0370)., Peer Reviewed, Postprint (published version)

Published
2021

5. The etransafe project on translational safety assessment through integrative knowledge management:Achievements and perspectives

Author

Pognan, François, Steger‐hartmann, Thomas, Díaz, Carlos, Blomberg, Niklas, Bringezu, Frank, Briggs, Katharine, Callegaro, Giulia, Capella‐gutierrez, Salvador, Centeno, Emilio, Corvi, Javier, Drew, Philip, Drewe, William C., Fernández, José M., Furlong, Laura I., Guney, Emre, Kors, Jan A., Mayer, Miguel Angel, Pastor, Manuel, Piñero, Janet, Ramírez‐anguita, Juan Manuel, Ronzano, Francesco, Rowell, Philip, Saüch‐pitarch, Josep, Valencia, Alfonso, van de Water, Bob, van der Lei, Johan, van Mulligen, Erik, Sanz, Ferran, Pognan, François, Steger‐hartmann, Thomas, Díaz, Carlos, Blomberg, Niklas, Bringezu, Frank, Briggs, Katharine, Callegaro, Giulia, Capella‐gutierrez, Salvador, Centeno, Emilio, Corvi, Javier, Drew, Philip, Drewe, William C., Fernández, José M., Furlong, Laura I., Guney, Emre, Kors, Jan A., Mayer, Miguel Angel, Pastor, Manuel, Piñero, Janet, Ramírez‐anguita, Juan Manuel, Ronzano, Francesco, Rowell, Philip, Saüch‐pitarch, Josep, Valencia, Alfonso, van de Water, Bob, van der Lei, Johan, van Mulligen, Erik, and Sanz, Ferran

Abstract

eTRANSAFE is a research project funded within the Innovative Medicines Initiative (IMI), which aims at developing integrated databases and computational tools (the eTRANSAFE ToxHub) that support the translational safety assessment of new drugs by using legacy data provided by the pharmaceutical companies that participate in the project. The project objectives include the development of databases containing preclinical and clinical data, computational systems for translational analysis including tools for data query, analysis and visualization, as well as computational models to explain and predict drug safety events.

Published
2021

6. GPCRmd uncovers the dynamics of the 3D-GPCRome

Author

Rodriguez-Espigares, Ismael, Torrens-Fontanals, Mariona, Tiemann, Johanna K. S., Aranda-Garcia, David, Manuel Ramirez-Anguita, Juan, Stepniewski, Tomasz Maciej, Worp, Nathalie, Varela-Rial, Alejandro, Morales-Pastor, Adrian, Medel-Lacruz, Brian, Pandy-Szekeres, Gaspar, Mayol, Eduardo, Giorgino, Toni, Carlsson, Jens, Deupi, Xavier, Filipek, Slawomir, Filizola, Marta, Carlos Gomez-Tamayo, Jose, Gonzalez, Angel, Gutiérrez-de-Terán, Hugo, Jimenez-Roses, Mireia, Jespers, Willem, Kapla, Jon, Khelashvili, George, Kolb, Peter, Latek, Dorota, Marti-Solano, Maria, Matricon, Pierre, Matsoukas, Minos-Timotheos, Miszta, Przemyslaw, Olivella, Mireia, Perez-Benito, Laura, Provasi, Davide, Rios, Santiago, Torrecillas, Ivan R., Sallander, Jessica, Sztyler, Agnieszka, Vasile, Silvana, Weinstein, Harel, Zachariae, Ulrich, Hildebrand, Peter W., De Fabritiis, Gianni, Sanz, Ferran, Gloriam, David E., Cordomi, Arnau, Guixa-Gonzalez, Ramon, Selent, Jana, Rodriguez-Espigares, Ismael, Torrens-Fontanals, Mariona, Tiemann, Johanna K. S., Aranda-Garcia, David, Manuel Ramirez-Anguita, Juan, Stepniewski, Tomasz Maciej, Worp, Nathalie, Varela-Rial, Alejandro, Morales-Pastor, Adrian, Medel-Lacruz, Brian, Pandy-Szekeres, Gaspar, Mayol, Eduardo, Giorgino, Toni, Carlsson, Jens, Deupi, Xavier, Filipek, Slawomir, Filizola, Marta, Carlos Gomez-Tamayo, Jose, Gonzalez, Angel, Gutiérrez-de-Terán, Hugo, Jimenez-Roses, Mireia, Jespers, Willem, Kapla, Jon, Khelashvili, George, Kolb, Peter, Latek, Dorota, Marti-Solano, Maria, Matricon, Pierre, Matsoukas, Minos-Timotheos, Miszta, Przemyslaw, Olivella, Mireia, Perez-Benito, Laura, Provasi, Davide, Rios, Santiago, Torrecillas, Ivan R., Sallander, Jessica, Sztyler, Agnieszka, Vasile, Silvana, Weinstein, Harel, Zachariae, Ulrich, Hildebrand, Peter W., De Fabritiis, Gianni, Sanz, Ferran, Gloriam, David E., Cordomi, Arnau, Guixa-Gonzalez, Ramon, and Selent, Jana

Abstract

G-protein-coupled receptors (GPCRs) are involved in numerous physiological processes and are the most frequent targets of approved drugs. The explosion in the number of new three-dimensional (3D) molecular structures of GPCRs (3D-GPCRome) over the last decade has greatly advanced the mechanistic understanding and drug design opportunities for this protein family. Molecular dynamics (MD) simulations have become a widely established technique for exploring the conformational landscape of proteins at an atomic level. However, the analysis and visualization of MD simulations require efficient storage resources and specialized software. Here we present GPCRmd (http://gpcrmd.org/), an online platform that incorporates web-based visualization capabilities as well as a comprehensive and user-friendly analysis toolbox that allows scientists from different disciplines to visualize, analyze and share GPCR MD data. GPCRmd originates from a community-driven effort to create an open, interactive and standardized database of GPCR MD simulations.

Published
2020
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7. GPCRmd uncovers the dynamics of the 3D-GPCRome

Author

Rodríguez-Espigares, Ismael, Torrens-Fontanals, Mariona, Tiemann, Johanna K. S., Aranda-García, David, Ramírez-Anguita, Juan Manuel, Stepniewski, Tomasz Maciej, Worp, Nathalie, Varela-Rial, Alejandro, Morales-Pastor, Adrián, Medel-Lacruz, Brian, Pándy-Szekeres, Gáspár, Mayol, Eduardo, Giorgino, Toni, Carlsson, Jens, Deupi, Xavier, Filipek, Slawomir, Filizola, Marta, Gómez-Tamayo, José Carlos, Gonzalez, Angel, Gutiérrez-de-Terán, Hugo, Jiménez-Rosés, Mireia, Jespers, Willem, Kapla, Jon, Khelashvili, George, Kolb, Peter, Latek, Dorota, Marti-Solano, Maria, Matricon, Pierre, Matsoukas, Minos-Timotheos, Miszta, Przemyslaw, Olivella, Mireia, Perez-Benito, Laura, Provasi, Davide, Ríos, Santiago, Torrecillas, Iván R., Sallander, Jessica, Sztyler, Agnieszka, Vasile, Silvana, Weinstein, Harel, Zachariae, Ulrich, Hildebrand, Peter W., De Fabritiis, Gianni, Sanz, Ferran, Gloriam, David E., Cordomi, Arnau, Guixà-González, Ramon, Selent, Jana, Rodríguez-Espigares, Ismael, Torrens-Fontanals, Mariona, Tiemann, Johanna K. S., Aranda-García, David, Ramírez-Anguita, Juan Manuel, Stepniewski, Tomasz Maciej, Worp, Nathalie, Varela-Rial, Alejandro, Morales-Pastor, Adrián, Medel-Lacruz, Brian, Pándy-Szekeres, Gáspár, Mayol, Eduardo, Giorgino, Toni, Carlsson, Jens, Deupi, Xavier, Filipek, Slawomir, Filizola, Marta, Gómez-Tamayo, José Carlos, Gonzalez, Angel, Gutiérrez-de-Terán, Hugo, Jiménez-Rosés, Mireia, Jespers, Willem, Kapla, Jon, Khelashvili, George, Kolb, Peter, Latek, Dorota, Marti-Solano, Maria, Matricon, Pierre, Matsoukas, Minos-Timotheos, Miszta, Przemyslaw, Olivella, Mireia, Perez-Benito, Laura, Provasi, Davide, Ríos, Santiago, Torrecillas, Iván R., Sallander, Jessica, Sztyler, Agnieszka, Vasile, Silvana, Weinstein, Harel, Zachariae, Ulrich, Hildebrand, Peter W., De Fabritiis, Gianni, Sanz, Ferran, Gloriam, David E., Cordomi, Arnau, Guixà-González, Ramon, and Selent, Jana

Abstract

G-protein-coupled receptors (GPCRs) are involved in numerous physiological processes and are the most frequent targets of approved drugs. The explosion in the number of new three-dimensional (3D) molecular structures of GPCRs (3D-GPCRome) over the last decade has greatly advanced the mechanistic understanding and drug design opportunities for this protein family. Molecular dynamics (MD) simulations have become a widely established technique for exploring the conformational landscape of proteins at an atomic level. However, the analysis and visualization of MD simulations require efficient storage resources and specialized software. Here we present GPCRmd (http://gpcrmd.org/), an online platform that incorporates web-based visualization capabilities as well as a comprehensive and user-friendly analysis toolbox that allows scientists from different disciplines to visualize, analyze and share GPCR MD data. GPCRmd originates from a community-driven effort to create an open, interactive and standardized database of GPCR MD simulations.

Published
2020

8. In Silico QT and APD Prolongation Assay for Early Screening of Drug-Induced Proarrhythmic Risk

Author

Universitat Politècnica de València. Departamento de Ingeniería Electrónica - Departament d'Enginyeria Electrònica, Innovative Medicines Initiative, Generalitat Valenciana, Ministerio de Economía, Industria y Competitividad, European Regional Development Fund, European Commission, Romero Pérez, Lucia, Cano-García, Jordi, Gomis-Tena Dolz, Julio, Trenor Gomis, Beatriz Ana, Sanz, Ferran, Pastor, Manuel, Saiz Rodríguez, Francisco Javier, Universitat Politècnica de València. Departamento de Ingeniería Electrónica - Departament d'Enginyeria Electrònica, Innovative Medicines Initiative, Generalitat Valenciana, Ministerio de Economía, Industria y Competitividad, European Regional Development Fund, European Commission, Romero Pérez, Lucia, Cano-García, Jordi, Gomis-Tena Dolz, Julio, Trenor Gomis, Beatriz Ana, Sanz, Ferran, Pastor, Manuel, and Saiz Rodríguez, Francisco Javier

Abstract

[EN] Drug-induced proarrhythmicity is a major concern for regulators and pharmaceutical companies. For novel drug candidates, the standard assessment involves the evaluation of the potassium hERG channels block and the in vivo prolongation of the QT interval. However, this method is known to be too restrictive and to stop the development of potentially valuable therapeutic drugs. The aim of this work is to create an in silico tool for early detection of drug-induced proarrhythmic risk. The system is based on simulations of how different compounds affect the action potential duration (APD) of isolated endocardial, midmyocardial, and epicardial cells as well as the QT prolongation in a virtual tissue. Multiple channel-drug interactions and state-of-the-art human ventricular action potential models (O'Hara, T., et al. PLos Comput. Biol. 2011, 7, e1002061) were used in our simulations. Specifically, 206.766 cellular and 7072 tissue simulations were performed by blocking the slow and the fast components of the delayed rectifier current (I-Ks and I-Kr, respectively) and the L-type calcium current (I-CaL) at different levels. The performance of our system was validated by classifying the proarrhythmic risk of 84 compounds, 40 of which present torsadogenic properties. On the basis of these results, we propose the use of a new index (Tx) for discriminating torsadogenic compounds, defined as the ratio of the drug concentrations producing 10% prolongation of the cellular endocardial, midmyocardial, and epicardial APDs and the QT interval, over the maximum effective free therapeutic plasma concentration (EFTPC). Our results show that the Tx index outperforms standard methods for early identification of torsadogenic compounds. Indeed, for the analyzed compounds, the Tx tests accuracy was in the range of 87-88% compared with a 73% accuracy of the hERG IC50 based test.

Published
2018

9. In Silico QT and APD Prolongation Assay for Early Screening of Drug-Induced Proarrhythmic Risk

Author

Universitat Politècnica de València. Departamento de Ingeniería Electrónica - Departament d'Enginyeria Electrònica, Innovative Medicines Initiative, Generalitat Valenciana, Ministerio de Economía, Industria y Competitividad, European Regional Development Fund, European Commission, Romero Pérez, Lucia, Cano-García, Jordi, Gomis-Tena Dolz, Julio, Trenor Gomis, Beatriz Ana, Sanz, Ferran, Pastor, Manuel, Saiz Rodríguez, Francisco Javier, Universitat Politècnica de València. Departamento de Ingeniería Electrónica - Departament d'Enginyeria Electrònica, Innovative Medicines Initiative, Generalitat Valenciana, Ministerio de Economía, Industria y Competitividad, European Regional Development Fund, European Commission, Romero Pérez, Lucia, Cano-García, Jordi, Gomis-Tena Dolz, Julio, Trenor Gomis, Beatriz Ana, Sanz, Ferran, Pastor, Manuel, and Saiz Rodríguez, Francisco Javier

Abstract

[EN] Drug-induced proarrhythmicity is a major concern for regulators and pharmaceutical companies. For novel drug candidates, the standard assessment involves the evaluation of the potassium hERG channels block and the in vivo prolongation of the QT interval. However, this method is known to be too restrictive and to stop the development of potentially valuable therapeutic drugs. The aim of this work is to create an in silico tool for early detection of drug-induced proarrhythmic risk. The system is based on simulations of how different compounds affect the action potential duration (APD) of isolated endocardial, midmyocardial, and epicardial cells as well as the QT prolongation in a virtual tissue. Multiple channel-drug interactions and state-of-the-art human ventricular action potential models (O'Hara, T., et al. PLos Comput. Biol. 2011, 7, e1002061) were used in our simulations. Specifically, 206.766 cellular and 7072 tissue simulations were performed by blocking the slow and the fast components of the delayed rectifier current (I-Ks and I-Kr, respectively) and the L-type calcium current (I-CaL) at different levels. The performance of our system was validated by classifying the proarrhythmic risk of 84 compounds, 40 of which present torsadogenic properties. On the basis of these results, we propose the use of a new index (Tx) for discriminating torsadogenic compounds, defined as the ratio of the drug concentrations producing 10% prolongation of the cellular endocardial, midmyocardial, and epicardial APDs and the QT interval, over the maximum effective free therapeutic plasma concentration (EFTPC). Our results show that the Tx index outperforms standard methods for early identification of torsadogenic compounds. Indeed, for the analyzed compounds, the Tx tests accuracy was in the range of 87-88% compared with a 73% accuracy of the hERG IC50 based test.

Published
2018

10. In Silico QT and APD Prolongation Assay for Early Screening of Drug-Induced Proarrhythmic Risk

Author

Universitat Politècnica de València. Departamento de Ingeniería Electrónica - Departament d'Enginyeria Electrònica, Innovative Medicines Initiative, Generalitat Valenciana, Ministerio de Economía, Industria y Competitividad, European Regional Development Fund, European Commission, Romero Pérez, Lucia, Cano-García, Jordi, Gomis-Tena Dolz, Julio, Trenor Gomis, Beatriz Ana, Sanz, Ferran, Pastor, Manuel, Saiz Rodríguez, Francisco Javier, Universitat Politècnica de València. Departamento de Ingeniería Electrónica - Departament d'Enginyeria Electrònica, Innovative Medicines Initiative, Generalitat Valenciana, Ministerio de Economía, Industria y Competitividad, European Regional Development Fund, European Commission, Romero Pérez, Lucia, Cano-García, Jordi, Gomis-Tena Dolz, Julio, Trenor Gomis, Beatriz Ana, Sanz, Ferran, Pastor, Manuel, and Saiz Rodríguez, Francisco Javier

Abstract

[EN] Drug-induced proarrhythmicity is a major concern for regulators and pharmaceutical companies. For novel drug candidates, the standard assessment involves the evaluation of the potassium hERG channels block and the in vivo prolongation of the QT interval. However, this method is known to be too restrictive and to stop the development of potentially valuable therapeutic drugs. The aim of this work is to create an in silico tool for early detection of drug-induced proarrhythmic risk. The system is based on simulations of how different compounds affect the action potential duration (APD) of isolated endocardial, midmyocardial, and epicardial cells as well as the QT prolongation in a virtual tissue. Multiple channel-drug interactions and state-of-the-art human ventricular action potential models (O'Hara, T., et al. PLos Comput. Biol. 2011, 7, e1002061) were used in our simulations. Specifically, 206.766 cellular and 7072 tissue simulations were performed by blocking the slow and the fast components of the delayed rectifier current (I-Ks and I-Kr, respectively) and the L-type calcium current (I-CaL) at different levels. The performance of our system was validated by classifying the proarrhythmic risk of 84 compounds, 40 of which present torsadogenic properties. On the basis of these results, we propose the use of a new index (Tx) for discriminating torsadogenic compounds, defined as the ratio of the drug concentrations producing 10% prolongation of the cellular endocardial, midmyocardial, and epicardial APDs and the QT interval, over the maximum effective free therapeutic plasma concentration (EFTPC). Our results show that the Tx index outperforms standard methods for early identification of torsadogenic compounds. Indeed, for the analyzed compounds, the Tx tests accuracy was in the range of 87-88% compared with a 73% accuracy of the hERG IC50 based test.

Published
2018

11. Adverse outcome pathways : opportunities, limitations and open questions

Author

Leist, Marcel, Ghallab, Ahmed, Graepel, Rabea, Marchan, Rosemarie, Hassan, Reham, Hougaard Bennekou, Susanne, Limonciel, Alice, Vinken, Mathieu, Schildknecht, Stefan, Waldmann, Tanja, Danen, Erik, van Ravenzwaay, Ben, Kamp, Hennicke, Gardner, Iain, Godoy, Patricio, Bois, Frederic Y., Braeuning, Albert, Reif, Raymond, Oesch, Franz, Drasdo, Dirk, Höhme, Stefan, Schwarz, Michael, Hartung, Thomas, Braunbeck, Thomas, Beltman, Joost, Vrieling, Harry, Sanz, Ferran, Forsby, Anna, Gadaleta, Domenico, Fisher, Ciaran, Kelm, Jens, Fluri, David, Ecker, Gerhard, Zdrazil, Barbara, Terron, Andrea, Jennings, Paul, van der Burg, Bart, Dooley, Steven, Meijer, Annemarie H., Willighagen, Egon, Martens, Marvin, Evelo, Chris, Mombelli, Enrico, Taboureau, Olivier, Mantovani, Alberto, Hardy, Barry, Koch, Bjorn, Escher, Sylvia, van Thriel, Christoph, Cadenas, Cristina, Kroese, D., van de Water, Bob, Hengstler, Jan G., Leist, Marcel, Ghallab, Ahmed, Graepel, Rabea, Marchan, Rosemarie, Hassan, Reham, Hougaard Bennekou, Susanne, Limonciel, Alice, Vinken, Mathieu, Schildknecht, Stefan, Waldmann, Tanja, Danen, Erik, van Ravenzwaay, Ben, Kamp, Hennicke, Gardner, Iain, Godoy, Patricio, Bois, Frederic Y., Braeuning, Albert, Reif, Raymond, Oesch, Franz, Drasdo, Dirk, Höhme, Stefan, Schwarz, Michael, Hartung, Thomas, Braunbeck, Thomas, Beltman, Joost, Vrieling, Harry, Sanz, Ferran, Forsby, Anna, Gadaleta, Domenico, Fisher, Ciaran, Kelm, Jens, Fluri, David, Ecker, Gerhard, Zdrazil, Barbara, Terron, Andrea, Jennings, Paul, van der Burg, Bart, Dooley, Steven, Meijer, Annemarie H., Willighagen, Egon, Martens, Marvin, Evelo, Chris, Mombelli, Enrico, Taboureau, Olivier, Mantovani, Alberto, Hardy, Barry, Koch, Bjorn, Escher, Sylvia, van Thriel, Christoph, Cadenas, Cristina, Kroese, D., van de Water, Bob, and Hengstler, Jan G.

Abstract

Adverse outcome pathways (AOPs) are a recent toxicological construct that connects, in a formalized, transparent and quality-controlled way, mechanistic information to apical endpoints for regulatory purposes. AOP links a molecular initiating event (MIE) to the adverse outcome (AO) via key events (KE), in a way specified by key event erelationships (KER). Although this approach to formalize mechanistic toxicological information only started in 2010, over 200 AOPs have already been established. At this stage, new requirements arise, such as the need for harmonization and re-assessment, for continuous updating, as well as for alerting about pitfalls, misuses and limits of applicability. In this review, the history of the AOP concept and its most prominent strengths are discussed, including the advantages of a formalized approach, the systematic collection of weight of evidence, the linkage of mechanisms to apical end points, the examination of the plausibility of epidemiological data, the identification of critical knowledge gaps and the design of mechanistic test methods. To prepare the ground for a broadened and appropriate use of AOPs, some widespread misconceptions are explained. Moreover, potential weaknesses and shortcomings of the current AOP rule set are addressed (1) to facilitate the discussion on its further evolution and (2) to better define appropriate vs. less suitable application areas. Exemplary toxicological studies are presented to discuss the linearity assumptions of AOP, the management of event modifiers and compensatory mechanisms, and whether a separation of toxicodynamics from toxicokinetics including metabolism is possible in the framework of pathway plasticity. Suggestions on how to compromise between different needs of AOP stakeholders have been added. A clear definition of open questions and limitations is provided to encourage further progress in the field.

Published
2017
Full Text
View/download PDF

12. Adverse outcome pathways: opportunities, limitations and open questions

Author

Leist, Marcel, Leist, Marcel, Ghallab, Ahmed, Graepel, Rabea, Marchan, Rosemarie, Hassan, Reham, Bennekou, Susanne Hougaard, Limonciel, Alice, Vinken, Mathieu, Schildknecht, Stefan, Waldmann, Tanja, Danen, Erik, van Ravenzwaay, Ben, Kamp, Hennicke, Gardner, Iain, Godoy, Patricio, Bois, Frederic Y., Braeuning, Albert, Reif, Raymond, Oesch, Franz, Drasdo, Dirk, Hoehme, Stefan, Schwarz, Michael, Hartung, Thomas, Braunbeck, Thomas, Beltman, Joost, Vrieling, Harry, Sanz, Ferran, Forsby, Anna, Gadaleta, Domenico, Fisher, Ciaran, Kelm, Jens, Fluri, David, Ecker, Gerhard, Zdrazil, Barbara, Terron, Andrea, Jennings, Paul, van der Burg, Bart, Dooley, Steven, Meijer, Annemarie H., Willighagen, Egon, Martens, Marvin, Evelo, Chris, Mombelli, Enrico, Taboureau, Olivier, Mantovani, Alberto, Hardy, Barry, Koch, Bjorn, Escher, Sylvia, van Thriel, Christoph, Cadenas, Cristina, Kroese, D., van de Water, Bob, Hengstler, Jan G., Leist, Marcel, Leist, Marcel, Ghallab, Ahmed, Graepel, Rabea, Marchan, Rosemarie, Hassan, Reham, Bennekou, Susanne Hougaard, Limonciel, Alice, Vinken, Mathieu, Schildknecht, Stefan, Waldmann, Tanja, Danen, Erik, van Ravenzwaay, Ben, Kamp, Hennicke, Gardner, Iain, Godoy, Patricio, Bois, Frederic Y., Braeuning, Albert, Reif, Raymond, Oesch, Franz, Drasdo, Dirk, Hoehme, Stefan, Schwarz, Michael, Hartung, Thomas, Braunbeck, Thomas, Beltman, Joost, Vrieling, Harry, Sanz, Ferran, Forsby, Anna, Gadaleta, Domenico, Fisher, Ciaran, Kelm, Jens, Fluri, David, Ecker, Gerhard, Zdrazil, Barbara, Terron, Andrea, Jennings, Paul, van der Burg, Bart, Dooley, Steven, Meijer, Annemarie H., Willighagen, Egon, Martens, Marvin, Evelo, Chris, Mombelli, Enrico, Taboureau, Olivier, Mantovani, Alberto, Hardy, Barry, Koch, Bjorn, Escher, Sylvia, van Thriel, Christoph, Cadenas, Cristina, Kroese, D., van de Water, Bob, and Hengstler, Jan G.

Abstract

Adverse outcome pathways (AOPs) are a recent toxicological construct that connects, in a formalized, transparent and quality-controlled way, mechanistic information to apical endpoints for regulatory purposes. AOP links a molecular initiating event (MIE) to the adverse outcome (AO) via key events (KE), in a way specified by key event erelationships (KER). Although this approach to formalize mechanistic toxicological information only started in 2010, over 200 AOPs have already been established. At this stage, new requirements arise, such as the need for harmonization and re-assessment, for continuous updating, as well as for alerting about pitfalls, misuses and limits of applicability. In this review, the history of the AOP concept and its most prominent strengths are discussed, including the advantages of a formalized approach, the systematic collection of weight of evidence, the linkage of mechanisms to apical end points, the examination of the plausibility of epidemiological data, the identification of critical knowledge gaps and the design of mechanistic test methods. To prepare the ground for a broadened and appropriate use of AOPs, some widespread misconceptions are explained. Moreover, potential weaknesses and shortcomings of the current AOP rule set are addressed (1) to facilitate the discussion on its further evolution and (2) to better define appropriate vs. less suitable application areas. Exemplary toxicological studies are presented to discuss the linearity assumptions of AOP, the management of event modifiers and compensatory mechanisms, and whether a separation of toxicodynamics from toxicokinetics including metabolism is possible in the framework of pathway plasticity. Suggestions on how to compromise between different needs of AOP stakeholders have been added. A clear definition of open questions and limitations is provided to encourage further progress in the field.

Published
2017

13. Legacy data sharing to improve drug safety assessment: the eTOX project

Author

Sanz, Ferran, Pognan, François, Steger-Hartmann, Thomas, Díaz, Carlos, Cases, Montserrat, Pastor, Manuel, Marc, Philippe, Wichard, Joerg, Briggs, Katharine, Watson, David K, Kleinöder, Thomas, Yang, Chihae, Amberg, Alexander, Beaumont, Maria, Brookes, Anthony J, Brunak, Søren, Cronin, Mark T D, Ecker, Gerhard F, Escher, Sylvia, Greene, Nigel, Guzmán, Antonio, Hersey, Anne, Jacques, Pascale, Lammens, Lieve, Mestres, Jordi, Muster, Wolfgang, Northeved, Helle, Pinches, Marc, Saiz, Javier, Sajot, Nicolas, Valencia, Alfonso, van der Lei, Johan, Vermeulen, Nico P E, Vock, Esther, Wolber, Gerhard, Zamora, Ismael, eTOX, Sanz, Ferran, Pognan, François, Steger-Hartmann, Thomas, Díaz, Carlos, Cases, Montserrat, Pastor, Manuel, Marc, Philippe, Wichard, Joerg, Briggs, Katharine, Watson, David K, Kleinöder, Thomas, Yang, Chihae, Amberg, Alexander, Beaumont, Maria, Brookes, Anthony J, Brunak, Søren, Cronin, Mark T D, Ecker, Gerhard F, Escher, Sylvia, Greene, Nigel, Guzmán, Antonio, Hersey, Anne, Jacques, Pascale, Lammens, Lieve, Mestres, Jordi, Muster, Wolfgang, Northeved, Helle, Pinches, Marc, Saiz, Javier, Sajot, Nicolas, Valencia, Alfonso, van der Lei, Johan, Vermeulen, Nico P E, Vock, Esther, Wolber, Gerhard, Zamora, Ismael, and eTOX

Abstract

The sharing of legacy preclinical safety data among pharmaceutical companies and its integration with other information sources offers unprecedented opportunities to improve the early assessment of drug safety. Here, we discuss the experience of the eTOX project, which was established through the Innovative Medicines Initiative to explore this possibility.

Published
2017
Full Text
View/download PDF

14. Adverse outcome pathways: opportunities, limitations and open questions

Author

Leist, Marcel, Ghallab, Ahmed, Graepel, Rabea, Marchan, Rosemarie, Hassan, Reham, Bennekou, Susanne Hougaard, Limonciel, Alice, Vinken, Mathieu, Schildknecht, Stefan, Waldmann, Tanja, Danen, Erik H J, van Ravenzwaay, Ben, Kamp, Hennicke, Gardner, Iain, Godoy, Patricio, Bois, Frederic Y, Braeuning, Albert, Reif, Raymond, Oesch, Franz, Drasdo, Dirk, Höhme, Stefan, Schwarz, Michael, Hartung, Thomas, Braunbeck, Thomas, Beltman, Joost, Vrieling, Harry, Sanz, Ferran, Forsby, Anna, Gadaleta, Domenico, Fisher, Ciarán, Kelm, Jens, Fluri, David, Ecker, Gerhard F., Zdrazil, Barbara, Terron, Andrea, Jennings, Paul, van der Burg, Bart, Dooley, Steven, Meijer, Annemarie H, Willighagen, Egon, Martens, Marvin, Evelo, Chris T., Mombelli, Enrico, Taboureau, Olivier, Mantovani, Alberto, Hardy, Barry, Koch, Bjorn, Escher, Sylvia, van Thriel, Christoph, Cadenas, Cristina, Kroese, D, van de Water, Bob, Hengstler, Jan G., Leist, Marcel, Ghallab, Ahmed, Graepel, Rabea, Marchan, Rosemarie, Hassan, Reham, Bennekou, Susanne Hougaard, Limonciel, Alice, Vinken, Mathieu, Schildknecht, Stefan, Waldmann, Tanja, Danen, Erik H J, van Ravenzwaay, Ben, Kamp, Hennicke, Gardner, Iain, Godoy, Patricio, Bois, Frederic Y, Braeuning, Albert, Reif, Raymond, Oesch, Franz, Drasdo, Dirk, Höhme, Stefan, Schwarz, Michael, Hartung, Thomas, Braunbeck, Thomas, Beltman, Joost, Vrieling, Harry, Sanz, Ferran, Forsby, Anna, Gadaleta, Domenico, Fisher, Ciarán, Kelm, Jens, Fluri, David, Ecker, Gerhard F., Zdrazil, Barbara, Terron, Andrea, Jennings, Paul, van der Burg, Bart, Dooley, Steven, Meijer, Annemarie H, Willighagen, Egon, Martens, Marvin, Evelo, Chris T., Mombelli, Enrico, Taboureau, Olivier, Mantovani, Alberto, Hardy, Barry, Koch, Bjorn, Escher, Sylvia, van Thriel, Christoph, Cadenas, Cristina, Kroese, D, van de Water, Bob, and Hengstler, Jan G.

Abstract

Adverse outcome pathways (AOPs) are a recent toxicological construct that connects, in a formalized, transparent and quality-controlled way, mechanistic information to apical endpoints for regulatory purposes. AOP links a molecular initiating event (MIE) to the adverse outcome (AO) via key events (KE), in a way specified by key event relationships (KER). Although this approach to formalize mechanistic toxicological information only started in 2010, over 200 AOPs have already been established. At this stage, new requirements arise, such as the need for harmonization and re-assessment, for continuous updating, as well as for alerting about pitfalls, misuses and limits of applicability. In this review, the history of the AOP concept and its most prominent strengths are discussed, including the advantages of a formalized approach, the systematic collection of weight of evidence, the linkage of mechanisms to apical end points, the examination of the plausibility of epidemiological data, the identification of critical knowledge gaps and the design of mechanistic test methods. To prepare the ground for a broadened and appropriate use of AOPs, some widespread misconceptions are explained. Moreover, potential weaknesses and shortcomings of the current AOP rule set are addressed (1) to facilitate the discussion on its further evolution and (2) to better define appropriate vs. less suitable application areas. Exemplary toxicological studies are presented to discuss the linearity assumptions of AOP, the management of event modifiers and compensatory mechanisms, and whether a separation of toxicodynamics from toxicokinetics including metabolism is possible in the framework of pathway plasticity. Suggestions on how to compromise between different needs of AOP stakeholders have been added. A clear definition of open questions and limitations is provided to encourage further progress in the field.

Published
2017
Full Text
View/download PDF

15. Adverse outcome pathways: opportunities, limitations and open questions

Author

Leist, Marcel, Ghallab, Ahmed, Graepel, Rabea, Marchan, Rosemarie, Hassan, Reham, Bennekou, Susanne Hougaard, Limonciel, Alice, Vinken, Mathieu, Schildknecht, Stefan, Waldmann, Tanja, Danen, Erik, van Ravenzwaay, Ben, Kamp, Hennicke, Gardner, Iain, Godoy, Patricio, Bois, Frederic Y., Braeuning, Albert, Reif, Raymond, Oesch, Franz, Drasdo, Dirk, Hoehme, Stefan, Schwarz, Michael, Hartung, Thomas, Braunbeck, Thomas, Beltman, Joost, Vrieling, Harry, Sanz, Ferran, Forsby, Anna, Gadaleta, Domenico, Fisher, Ciaran, Kelm, Jens, Fluri, David, Ecker, Gerhard, Zdrazil, Barbara, Terron, Andrea, Jennings, Paul, van der Burg, Bart, Dooley, Steven, Meijer, Annemarie H., Willighagen, Egon, Martens, Marvin, Evelo, Chris, Mombelli, Enrico, Taboureau, Olivier, Mantovani, Alberto, Hardy, Barry, Koch, Bjorn, Escher, Sylvia, van Thriel, Christoph, Cadenas, Cristina, Kroese, D., van de Water, Bob, Hengstler, Jan G., Leist, Marcel, Ghallab, Ahmed, Graepel, Rabea, Marchan, Rosemarie, Hassan, Reham, Bennekou, Susanne Hougaard, Limonciel, Alice, Vinken, Mathieu, Schildknecht, Stefan, Waldmann, Tanja, Danen, Erik, van Ravenzwaay, Ben, Kamp, Hennicke, Gardner, Iain, Godoy, Patricio, Bois, Frederic Y., Braeuning, Albert, Reif, Raymond, Oesch, Franz, Drasdo, Dirk, Hoehme, Stefan, Schwarz, Michael, Hartung, Thomas, Braunbeck, Thomas, Beltman, Joost, Vrieling, Harry, Sanz, Ferran, Forsby, Anna, Gadaleta, Domenico, Fisher, Ciaran, Kelm, Jens, Fluri, David, Ecker, Gerhard, Zdrazil, Barbara, Terron, Andrea, Jennings, Paul, van der Burg, Bart, Dooley, Steven, Meijer, Annemarie H., Willighagen, Egon, Martens, Marvin, Evelo, Chris, Mombelli, Enrico, Taboureau, Olivier, Mantovani, Alberto, Hardy, Barry, Koch, Bjorn, Escher, Sylvia, van Thriel, Christoph, Cadenas, Cristina, Kroese, D., van de Water, Bob, and Hengstler, Jan G.

Abstract

Adverse outcome pathways (AOPs) are a recent toxicological construct that connects, in a formalized, transparent and quality-controlled way, mechanistic information to apical endpoints for regulatory purposes. AOP links a molecular initiating event (MIE) to the adverse outcome (AO) via key events (KE), in a way specified by key event erelationships (KER). Although this approach to formalize mechanistic toxicological information only started in 2010, over 200 AOPs have already been established. At this stage, new requirements arise, such as the need for harmonization and re-assessment, for continuous updating, as well as for alerting about pitfalls, misuses and limits of applicability. In this review, the history of the AOP concept and its most prominent strengths are discussed, including the advantages of a formalized approach, the systematic collection of weight of evidence, the linkage of mechanisms to apical end points, the examination of the plausibility of epidemiological data, the identification of critical knowledge gaps and the design of mechanistic test methods. To prepare the ground for a broadened and appropriate use of AOPs, some widespread misconceptions are explained. Moreover, potential weaknesses and shortcomings of the current AOP rule set are addressed (1) to facilitate the discussion on its further evolution and (2) to better define appropriate vs. less suitable application areas. Exemplary toxicological studies are presented to discuss the linearity assumptions of AOP, the management of event modifiers and compensatory mechanisms, and whether a separation of toxicodynamics from toxicokinetics including metabolism is possible in the framework of pathway plasticity. Suggestions on how to compromise between different needs of AOP stakeholders have been added. A clear definition of open questions and limitations is provided to encourage further progress in the field.

Published
2017

16. Adverse outcome pathways:opportunities, limitations and open questions

Author

Leist, Marcel, Ghallab, Ahmed, Graepel, Rabea, Marchan, Rosemarie, Hassan, Reham, Bennekou, Susanne Hougaard, Limonciel, Alice, Vinken, Mathieu, Schildknecht, Stefan, Waldmann, Tanja, Danen, Erik, van Ravenzwaay, Ben, Kamp, Hennicke, Gardner, Iain, Godoy, Patricio, Bois, Frederic Y, Braeuning, Albert, Reif, Raymond, Oesch, Franz, Drasdo, Dirk, Höhme, Stefan, Schwarz, Michael, Hartung, Thomas, Braunbeck, Thomas, Beltman, Joost, Vrieling, Harry, Sanz, Ferran, Forsby, Anna, Gadaleta, Domenico, Fisher, Ciarán, Kelm, Jens, Fluri, David, Ecker, Gerhard, Zdrazil, Barbara, Terron, Andrea, Jennings, Paul, van der Burg, Bart, Dooley, Steven, Meijer, Annemarie H, Willighagen, Egon, Martens, Marvin, Evelo, Chris, Mombelli, Enrico, Taboureau, Olivier, Mantovani, Alberto, Hardy, Barry, Koch, Bjorn, Escher, Sylvia, van Thriel, Christoph, Cadenas, Cristina, Kroese, D, van de Water, Bob, Hengstler, Jan G, Leist, Marcel, Ghallab, Ahmed, Graepel, Rabea, Marchan, Rosemarie, Hassan, Reham, Bennekou, Susanne Hougaard, Limonciel, Alice, Vinken, Mathieu, Schildknecht, Stefan, Waldmann, Tanja, Danen, Erik, van Ravenzwaay, Ben, Kamp, Hennicke, Gardner, Iain, Godoy, Patricio, Bois, Frederic Y, Braeuning, Albert, Reif, Raymond, Oesch, Franz, Drasdo, Dirk, Höhme, Stefan, Schwarz, Michael, Hartung, Thomas, Braunbeck, Thomas, Beltman, Joost, Vrieling, Harry, Sanz, Ferran, Forsby, Anna, Gadaleta, Domenico, Fisher, Ciarán, Kelm, Jens, Fluri, David, Ecker, Gerhard, Zdrazil, Barbara, Terron, Andrea, Jennings, Paul, van der Burg, Bart, Dooley, Steven, Meijer, Annemarie H, Willighagen, Egon, Martens, Marvin, Evelo, Chris, Mombelli, Enrico, Taboureau, Olivier, Mantovani, Alberto, Hardy, Barry, Koch, Bjorn, Escher, Sylvia, van Thriel, Christoph, Cadenas, Cristina, Kroese, D, van de Water, Bob, and Hengstler, Jan G

Abstract

Adverse outcome pathways (AOPs) are a recent toxicological construct that connects, in a formalized, transparent and quality-controlled way, mechanistic information to apical endpoints for regulatory purposes. AOP links a molecular initiating event (MIE) to the adverse outcome (AO) via key events (KE), in a way specified by key event relationships (KER). Although this approach to formalize mechanistic toxicological information only started in 2010, over 200 AOPs have already been established. At this stage, new requirements arise, such as the need for harmonization and re-assessment, for continuous updating, as well as for alerting about pitfalls, misuses and limits of applicability. In this review, the history of the AOP concept and its most prominent strengths are discussed, including the advantages of a formalized approach, the systematic collection of weight of evidence, the linkage of mechanisms to apical end points, the examination of the plausibility of epidemiological data, the identification of critical knowledge gaps and the design of mechanistic test methods. To prepare the ground for a broadened and appropriate use of AOPs, some widespread misconceptions are explained. Moreover, potential weaknesses and shortcomings of the current AOP rule set are addressed (1) to facilitate the discussion on its further evolution and (2) to better define appropriate vs. less suitable application areas. Exemplary toxicological studies are presented to discuss the linearity assumptions of AOP, the management of event modifiers and compensatory mechanisms, and whether a separation of toxicodynamics from toxicokinetics including metabolism is possible in the framework of pathway plasticity. Suggestions on how to compromise between different needs of AOP stakeholders have been added. A clear definition of open questions and limitations is provided to encourage further progress in the field.

Published
2017

17. Discussion of “the new role of biomedical informatics in the age of digital medicine”

Author

Al-Shorbaji, Najeeb, Bellazzi, Riccardo, Gonzalez Bernaldo de Quiros, Fernan, Koch, Sabine, Kulikowski, Casimir A., Lovell, Nigel H., Maojo García, Víctor Manuel, Park, Hyeoun-Ae, Sanz, Ferran, Sarkar, Indra N., Tanaka, Hiroshi, Al-Shorbaji, Najeeb, Bellazzi, Riccardo, Gonzalez Bernaldo de Quiros, Fernan, Koch, Sabine, Kulikowski, Casimir A., Lovell, Nigel H., Maojo García, Víctor Manuel, Park, Hyeoun-Ae, Sanz, Ferran, Sarkar, Indra N., and Tanaka, Hiroshi

Abstract

This article is part of a For-Discussion-Section of Methods of Information in Medicine about the paper “The New Role of Biomedical Informatics in the Age of Digital Medicine” written by Fernando J. Martin-Sanchez and Guillermo H. Lopez-Campos. It is introduced by an editorial. This article contains the combined commentaries invited to in -dependently comment on the paper of Martin-Sanchez and Lopez-Campos. In subsequent issues the discussion can continue through letters to the editor.

Published
2016

18. Improving data and knowledge management to better integrate health care and research

Author

Cases, Montserrat, Furlong, Laura I., Albanell, Joan, Altman, Russ B., Bellazzi, Riccardo, Boyer, Scott, Brand, Angela, Brookes, Anthony J., Brunak, Soren, Clark, Timothy W., Gea, Joaquim, Ghazal, Peter, Graf, Norbert, Guigo, Roderic, Klein, Teri E., Lopez-Bigas, Nuria, Maojo, Victor, Mons, Barend, Musen, Mark, Oliveira, José L., Rowe, Anthony, Ruch, Patrick, Shabo, Amnon, Shortliffe, Edward H., Valencia, Alfonso, van der Lei, Johan, Mayer, Miguel A., Sanz, Ferran, Cases, Montserrat, Furlong, Laura I., Albanell, Joan, Altman, Russ B., Bellazzi, Riccardo, Boyer, Scott, Brand, Angela, Brookes, Anthony J., Brunak, Soren, Clark, Timothy W., Gea, Joaquim, Ghazal, Peter, Graf, Norbert, Guigo, Roderic, Klein, Teri E., Lopez-Bigas, Nuria, Maojo, Victor, Mons, Barend, Musen, Mark, Oliveira, José L., Rowe, Anthony, Ruch, Patrick, Shabo, Amnon, Shortliffe, Edward H., Valencia, Alfonso, van der Lei, Johan, Mayer, Miguel A., and Sanz, Ferran

Abstract

Medicine is an increasingly data intensive discipline, with a growing need to link individual patient health records to rapidly changing research knowledge for better differential diagnosis, prognosis, and prediction of treatment response. Equally, biomedical research will gain massively from the integrative analysis of clinical and multi-omics information. Capitalizing on these opportunities must be guided by a precise understanding of many complex issues related to the integration of large amounts of diverse information. Partly this involves overcoming barriers between different disciplines, such as biology, medicine and computer sciences – implying a key role for ‘knowledge engineers’. This paper summarizes recent expert debates on such matters, leading to suggestions for concrete actions that should improve and better synergize both research and healthcare.

Published
2014

19. Nanoinformatics: developing new computing applications for nanomedicine

Author

Maojo Garcia, Victor Manuel, Fritts, Martin, Martín-Sánchez, Fernando, Iglesia Jimenez, Diana de la, Cachau, Raul E., García Remesal, Miguel, Crespo del Arco, Jose, Mitchell, Joyce A., Anguita Sanchez, Alberto, Baker, Nathan, Barreiro Sorrivas, Jose Maria, Benitez, Sonia E., Calle, Guillermo de la, Facelli, Julio C., Ghazal, Peter, Geissbuhler, Antoine, González-Nilo, Fernando D., Norbert, Graf, Grangeat, Pierre, Hermosilla, Isabel, Hussein, Rada, Kern, Josipa, Koch, Sabine, Legre, Yannick, Lopez-Alonso, Victoria, Lopez-Campos, Guillermo, Milanesi, Luciano, Moustakis, Vassilis, Munteanu, Cristian, Otero, Paula, Pazos Sierra, Alejandro, Perez Rey, David, Potamias, George, Sanz, Ferran, Kulikowski, Casimir, Maojo Garcia, Victor Manuel, Fritts, Martin, Martín-Sánchez, Fernando, Iglesia Jimenez, Diana de la, Cachau, Raul E., García Remesal, Miguel, Crespo del Arco, Jose, Mitchell, Joyce A., Anguita Sanchez, Alberto, Baker, Nathan, Barreiro Sorrivas, Jose Maria, Benitez, Sonia E., Calle, Guillermo de la, Facelli, Julio C., Ghazal, Peter, Geissbuhler, Antoine, González-Nilo, Fernando D., Norbert, Graf, Grangeat, Pierre, Hermosilla, Isabel, Hussein, Rada, Kern, Josipa, Koch, Sabine, Legre, Yannick, Lopez-Alonso, Victoria, Lopez-Campos, Guillermo, Milanesi, Luciano, Moustakis, Vassilis, Munteanu, Cristian, Otero, Paula, Pazos Sierra, Alejandro, Perez Rey, David, Potamias, George, Sanz, Ferran, and Kulikowski, Casimir

Abstract

Nanoinformatics has recently emerged to address the need of computing applications at the nano level. In this regard, the authors have participated in various initiatives to identify its concepts, foundations and challenges. While nanomaterials open up the possibility for developing new devices in many industrial and scientific areas, they also offer breakthrough perspectives for the prevention, diagnosis and treatment of diseases. In this paper, we analyze the different aspects of nanoinformatics and suggest five research topics to help catalyze new research and development in the area, particularly focused on nanomedicine. We also encompass the use of informatics to further the biological and clinical applications of basic research in nanoscience and nanotechnology, and the related concept of an extended ?nanotype? to coalesce information related to nanoparticles. We suggest how nanoinformatics could accelerate developments in nanomedicine, similarly to what happened with the Human Genome and other -omics projects, on issues like exchanging modeling and simulation methods and tools, linking toxicity information to clinical and personal databases or developing new approaches for scientific ontologies, among many others.

Published
2012

20. Nanoinformatics: developing new computing applications for nanomedicine

Author

Maojo García, Víctor Manuel, Fritts, Martin, Martín-Sánchez, Fernando, Iglesia Jimenez, Diana de la, Cachau, Raul E., García Remesal, Miguel, Crespo del Arco, Jose, Mitchell, Joyce A., Anguita Sanchez, Alberto, Baker, Nathan, Barreiro Sorrivas, Jose Maria, Benitez, Sonia E., Calle, Guillermo de la, Facelli, Julio C., Ghazal, Peter, Geissbuhler, Antoine, González-Nilo, Fernando D., Norbert, Graf, Grangeat, Pierre, Hermosilla, Isabel, Hussein, Rada, Kern, Josipa, Koch, Sabine, Legre, Yannick, Lopez-Alonso, Victoria, Lopez-Campos, Guillermo, Milanesi, Luciano, Moustakis, Vassilis, Munteanu, Cristian, Otero, Paula, Pazos Sierra, Alejandro, Perez Rey, David, Potamias, George, Sanz, Ferran, Kulikowski, Casimir, Maojo García, Víctor Manuel, Fritts, Martin, Martín-Sánchez, Fernando, Iglesia Jimenez, Diana de la, Cachau, Raul E., García Remesal, Miguel, Crespo del Arco, Jose, Mitchell, Joyce A., Anguita Sanchez, Alberto, Baker, Nathan, Barreiro Sorrivas, Jose Maria, Benitez, Sonia E., Calle, Guillermo de la, Facelli, Julio C., Ghazal, Peter, Geissbuhler, Antoine, González-Nilo, Fernando D., Norbert, Graf, Grangeat, Pierre, Hermosilla, Isabel, Hussein, Rada, Kern, Josipa, Koch, Sabine, Legre, Yannick, Lopez-Alonso, Victoria, Lopez-Campos, Guillermo, Milanesi, Luciano, Moustakis, Vassilis, Munteanu, Cristian, Otero, Paula, Pazos Sierra, Alejandro, Perez Rey, David, Potamias, George, Sanz, Ferran, and Kulikowski, Casimir

Abstract

Nanoinformatics has recently emerged to address the need of computing applications at the nano level. In this regard, the authors have participated in various initiatives to identify its concepts, foundations and challenges. While nanomaterials open up the possibility for developing new devices in many industrial and scientific areas, they also offer breakthrough perspectives for the prevention, diagnosis and treatment of diseases. In this paper, we analyze the different aspects of nanoinformatics and suggest five research topics to help catalyze new research and development in the area, particularly focused on nanomedicine. We also encompass the use of informatics to further the biological and clinical applications of basic research in nanoscience and nanotechnology, and the related concept of an extended ?nanotype? to coalesce information related to nanoparticles. We suggest how nanoinformatics could accelerate developments in nanomedicine, similarly to what happened with the Human Genome and other -omics projects, on issues like exchanging modeling and simulation methods and tools, linking toxicity information to clinical and personal databases or developing new approaches for scientific ontologies, among many others.

Published
2012

21. Knowledge engineering for health:a new discipline required to bridge the 'ICT gap' between research and healthcare

Author

Beck, Tim, Gollapudi, Sirisha, Brunak, Søren, Graf, Norbert, Lemke, Heinz U, Dash, Debasis, Buchan, Iain, Díaz, Carlos, Sanz, Ferran, Brookes, Anthony J, Beck, Tim, Gollapudi, Sirisha, Brunak, Søren, Graf, Norbert, Lemke, Heinz U, Dash, Debasis, Buchan, Iain, Díaz, Carlos, Sanz, Ferran, and Brookes, Anthony J

Abstract

Despite vast amount of money and research being channeled toward biomedical research, relatively little impact has been made on routine clinical practice. At the heart of this failure is the information and communication technology "chasm" that exists between research and healthcare. A new focus on "knowledge engineering for health" is needed to facilitate knowledge transmission across the research-healthcare gap. This discipline is required to engineer the bidirectional flow of data: processing research data and knowledge to identify clinically relevant advances and delivering these into healthcare use; conversely, making outcomes from the practice of medicine suitably available for use by the research community. This system will be able to self-optimize in that outcomes for patients treated by decisions that were based on the latest research knowledge will be fed back to the research world. A series of meetings, culminating in the "I-Health 2011" workshop, have brought together interdisciplinary experts to map the challenges and requirements for such a system. Here, we describe the main conclusions from these meetings. An "I4Health" interdisciplinary network of experts now exists to promote the key aims and objectives, namely "integrating and interpreting information for individualized healthcare," by developing the "knowledge engineering for health" domain.

Published
2012

22. Knowledge engineering for health:a new discipline required to bridge the 'ICT gap' between research and healthcare

Author

Beck, Tim, Gollapudi, Sirisha, Brunak, Søren, Graf, Norbert, Lemke, Heinz U, Dash, Debasis, Buchan, Iain, Díaz, Carlos, Sanz, Ferran, Brookes, Anthony J, Beck, Tim, Gollapudi, Sirisha, Brunak, Søren, Graf, Norbert, Lemke, Heinz U, Dash, Debasis, Buchan, Iain, Díaz, Carlos, Sanz, Ferran, and Brookes, Anthony J

Abstract

Despite vast amount of money and research being channeled toward biomedical research, relatively little impact has been made on routine clinical practice. At the heart of this failure is the information and communication technology "chasm" that exists between research and healthcare. A new focus on "knowledge engineering for health" is needed to facilitate knowledge transmission across the research-healthcare gap. This discipline is required to engineer the bidirectional flow of data: processing research data and knowledge to identify clinically relevant advances and delivering these into healthcare use; conversely, making outcomes from the practice of medicine suitably available for use by the research community. This system will be able to self-optimize in that outcomes for patients treated by decisions that were based on the latest research knowledge will be fed back to the research world. A series of meetings, culminating in the "I-Health 2011" workshop, have brought together interdisciplinary experts to map the challenges and requirements for such a system. Here, we describe the main conclusions from these meetings. An "I4Health" interdisciplinary network of experts now exists to promote the key aims and objectives, namely "integrating and interpreting information for individualized healthcare," by developing the "knowledge engineering for health" domain.

Published
2012

23. 'Cor d'atleta' avaluació ecocardiogràfica

Author

Martínez Muñoz, Agustín, Sanz, Ferran, Molina i Ferragut, Lluís, Universitat Autònoma de Barcelona. Departament de Medicina, Martínez Muñoz, Agustín, Sanz, Ferran, Molina i Ferragut, Lluís, and Universitat Autònoma de Barcelona. Departament de Medicina

Abstract

Descripció del recurs: 10 setembre de 2010

Published
2010

24. 'Cor d'atleta' : avaluació ecocardiogràfica

Author

Martínez Muñoz, Agustín, Sanz, Ferran, Molina i Ferragut, Lluís, Universitat Autònoma de Barcelona. Departament de Medicina, Martínez Muñoz, Agustín, Sanz, Ferran, Molina i Ferragut, Lluís, and Universitat Autònoma de Barcelona. Departament de Medicina

Abstract

Descripció del recurs: 10 setembre de 2010

Published
2010

25. 'Cor d'atleta' avaluació ecocardiogràfica

Author

Martínez Muñoz, Agustín, Sanz, Ferran, Molina i Ferragut, Lluís, Universitat Autònoma de Barcelona. Departament de Medicina, Martínez Muñoz, Agustín, Sanz, Ferran, Molina i Ferragut, Lluís, and Universitat Autònoma de Barcelona. Departament de Medicina

Abstract

Descripció del recurs: 10 setembre de 2010

Published
2010

27. Formación en Informática Biomédica. Red INBIOMED

Author

Universitat Politècnica de València. Escuela Técnica Superior de Ingenieros Industriales - Escola Tècnica Superior d'Enginyers Industrials, Universitat Politècnica de València. Escola Tècnica Superior d'Enginyeria Informàtica, Robles Viejo, Montserrat, García Gómez, Juan Miguel, López, Victoria, Martín, Fernando, Dafonte, Carlos, Corella, Dolores, Bueno, Gloria, Díaz, Juan, Coltell, Óscar, Pastor, Xavier, Sanz, Ferran, Maojo, Víctor, Universitat Politècnica de València. Escuela Técnica Superior de Ingenieros Industriales - Escola Tècnica Superior d'Enginyers Industrials, Universitat Politècnica de València. Escola Tècnica Superior d'Enginyeria Informàtica, Robles Viejo, Montserrat, García Gómez, Juan Miguel, López, Victoria, Martín, Fernando, Dafonte, Carlos, Corella, Dolores, Bueno, Gloria, Díaz, Juan, Coltell, Óscar, Pastor, Xavier, Sanz, Ferran, and Maojo, Víctor

Published
2004

28. Formación en Informática Biomédica. Red INBIOMED

Author

Universitat Politècnica de València. Escuela Técnica Superior de Ingenieros Industriales - Escola Tècnica Superior d'Enginyers Industrials, Universitat Politècnica de València. Escola Tècnica Superior d'Enginyeria Informàtica, Robles Viejo, Montserrat, García Gómez, Juan Miguel, López, Victoria, Martín, Fernando, Dafonte, Carlos, Corella, Dolores, Bueno, Gloria, Díaz, Juan, Coltell, Óscar, Pastor, Xavier, Sanz, Ferran, Maojo, Víctor, Universitat Politècnica de València. Escuela Técnica Superior de Ingenieros Industriales - Escola Tècnica Superior d'Enginyers Industrials, Universitat Politècnica de València. Escola Tècnica Superior d'Enginyeria Informàtica, Robles Viejo, Montserrat, García Gómez, Juan Miguel, López, Victoria, Martín, Fernando, Dafonte, Carlos, Corella, Dolores, Bueno, Gloria, Díaz, Juan, Coltell, Óscar, Pastor, Xavier, Sanz, Ferran, and Maojo, Víctor

Published
2004

29. Validating SPONGIA, an expert system for sponge identification

Author

Comisión Interministerial de Ciencia y Tecnología, CICYT (España), Generalitat de Catalunya, Domingo, Marta, Martin-Baranera, Montserrat, Sanz, Ferran, Sierra, Carles, Uriz, María Jesús, Comisión Interministerial de Ciencia y Tecnología, CICYT (España), Generalitat de Catalunya, Domingo, Marta, Martin-Baranera, Montserrat, Sanz, Ferran, Sierra, Carles, and Uriz, María Jesús

Abstract

In this article we present the validation of SPONGIA, an expert system to help in the identification of marine sponges. Validation was performed by using data from 82 randomly selected literature descriptions of sponge species. The data gathered by SPONGIA to identify each specimen were obtained from the bibliographical description. The set of cases, in which each case was described by the data gathered by SPONGIA, was presented to five internationally recognised experts in sponge systematics. The identifications generated by SPONGIA were compared with the identifications of these human experts by means of a cluster analysis. The similarity between SPONGIA and human identifications was assessed using four measures: Euclidean distance, City-block distance, Mahalanobis distance and Kappa index. In this article we show that SPONGIA obtains similar quality results to the experts in Porifera systematics. © 1999 Elsevier Science Ltd. All rights reserved.

Published
1999

30. Validation of the Medical Expert System RENOIR

Author

Hernandez, Christine, Sancho, Joan J., Belmonte, Miguel A., Sierra, Carles, Sanz, Ferran, Hernandez, Christine, Sancho, Joan J., Belmonte, Miguel A., Sierra, Carles, and Sanz, Ferran

Abstract

RENOIR is an expert system developed to assist the diagnosis of 37 diseases of connective tissue and inflammatory arthropathies. Precise diagnosis of rheumatic diseases implies great uncertainty and there is no gold standard with which to compare the expert system output. To overcome this problem a set of clinical cases was submitted to RENOIR and its diagnoses were compared with those of clinicians. Medical records or 81 patients with rheumatic diseases were interpreted by RENOIR and by 12 clinicians at three different expertise levels in rheumatology. Distances between the likelihoods of the 37 considered diseases provided by clinicians and RENOIR were computed as a disagreement measure. Mahalanobis distance was used to correct the collinearity between the possibilities of each pair of diseases. Using the resulting matrices of distances between experts, cluster analyses were carried out to classify RENOIR among human experts. Greater differences between RENOIR and clinicians than among clinicians themselves were not found. © 1994 Academic Press. All rights reserved.

Published
1994

31. Four-month incidence of suicidal thoughts and behaviors among healthcare workers after the first wave of the Spain COVID-19 pandemic

Author

Medicina Preventiva, Mortier, P., Vilagut, G., Alayo, I., Ferrer, M., Amigo, F., Aragonès, E., Aragón-Peña, A., Asúnsolo del Barco, A., Campos, M., Espuga, M., González-Pinto, A., Haro, J.M., López Fresneña, N., Martínez de Salázar, A., Molina, J.D., Ortí-Lucas, R.M., Parellada, M., Pérez-Gómez, B., Pérez-Zapata, A., Pijoan, J.I., Plana, N., Polentinos-Castro, E., Portillo-Van Diest, A., Puig, M.T., Rius, C., Sanz, F., Serra, C., Urreta-Barallobre, I., Kessler, R.C., Bruffaerts, R., Vieta, E., Pérez-Solá, V., Alonso, J., Alonso, Jordi, Alayo, Itxaso, Alonso, Manuel, Álvarez, Mar, Amann, Benedikt, Amigo, Franco F., Anmella, Gerard, Aragón, Andres, Aragonés, Nuria, Aragonès, Enric, Arizón, Ana Isabel, Asunsolo, Angel, Ayora, Alfons, Ballester, Laura, Barbas, Puri, Basora, Josep, Bereciartua, Elena, Ignasi Bolibar, Inés Bravo, Bonfill, Xavier, Cotillas, Alberto, Cuartero, Andres, de Paz, Concha, Cura, Isabel del, Jesus del Yerro, Maria, Diaz, Domingo, Domingo, Jose Luis, Emparanza, Jose I., Espallargues, Mireia, Espuga, Meritxell, Estevan, Patricia, Fernandez, M. Isabel, Ferrer, Montse, Ferreres, Yolanda, Fico, Giovanna, Forjaz, M. Joao, Barranco, Rosa Garcia, Garcia TorrecillasC Garcia-Ribera, J. Manuel, Garrido, Araceli, Gil, Elisa, Gomez, Marta, Gomez, Javier, Pinto, Ana Gonzalez, Haro, Josep Maria, Hernando, Margarita, Insigna, Maria Giola, Iriberri, Milagros, Jimenez, Nuria, Jimenez, Xavi, Larrauri, Amparo, Leon, Fernando, Lopez-Fresneña, Nieves, Lopez, Carmen, Lopez-Atanes Juan Antonio Lopez-Rodriguez, Mayte, Lopez-Cortacans, German, Martin, Jesus, Martinez-Cortés, Mercedes, Martinez-Martinez, Raquel, Martinez de Salazar, Alma D., Martinez, Isabel, Marzola, Marco, Mata, Nelva, Molina, Josep Maria, de Dios Molina, Juan, Molinero, Emilia, Mortier, Philippe, Muñoz, Carmen, Murru, Andrea, Olmedo, Jorge, Ortí, Rafael M., Padrós, Rafael, Pallejà, Meritxell, Parra, Raul, Pascual, Julio, Pelayo, Jose Maria, Pla, Rosa, Plana, Nieves, Aznar, Coro Perez, Gomez, Beatriz Perez, Zapata, Aurora Perez, Pijoan, Jose Ignacio, Polentinos, Elena, Puertolas, Beatriz, Puig, Maria Teresa, Quílez, Alex, Quintana, M. Jesus, Quiroga, Antonio, Rentero, David, Rey, Cristina, Rius, Cristina, Rodriguez-Blazquez, Carmen, Rojas, M. Jose, Romero, Yamina, Rubio, Gabriel, Rumayor, Mercedes, Ruiz, Pedro, Saenz, Margarita, Sanchez, Jesus, Sanchez-Arcilla, Ignacio, Sanz, Ferran, Serra, Consol, Serra-Sutton, Victoria, Serrano, Manuela, Sola, Silvia, Solera, Sara, Soto, Miguel, Tarrago, Alejandra, Tolosa, Natividad, Vazquez, Mireia, Viciola, Margarita, Vieta, Eduard, Vilagut, Gemma, Yago, Sara, Yañez, Jesus, Zapico, Yolanda, Zorita, Luis Maria, Zorrilla, Iñaki, Zurbano, Saioa L., Perez-Solá, Victor, Pelayo Terán, J.M, Fernández Villa, Tania, Marcos Delgado, Alba, Martín Sánchez, Vicente, Medicina Preventiva, Mortier, P., Vilagut, G., Alayo, I., Ferrer, M., Amigo, F., Aragonès, E., Aragón-Peña, A., Asúnsolo del Barco, A., Campos, M., Espuga, M., González-Pinto, A., Haro, J.M., López Fresneña, N., Martínez de Salázar, A., Molina, J.D., Ortí-Lucas, R.M., Parellada, M., Pérez-Gómez, B., Pérez-Zapata, A., Pijoan, J.I., Plana, N., Polentinos-Castro, E., Portillo-Van Diest, A., Puig, M.T., Rius, C., Sanz, F., Serra, C., Urreta-Barallobre, I., Kessler, R.C., Bruffaerts, R., Vieta, E., Pérez-Solá, V., Alonso, J., Alonso, Jordi, Alayo, Itxaso, Alonso, Manuel, Álvarez, Mar, Amann, Benedikt, Amigo, Franco F., Anmella, Gerard, Aragón, Andres, Aragonés, Nuria, Aragonès, Enric, Arizón, Ana Isabel, Asunsolo, Angel, Ayora, Alfons, Ballester, Laura, Barbas, Puri, Basora, Josep, Bereciartua, Elena, Ignasi Bolibar, Inés Bravo, Bonfill, Xavier, Cotillas, Alberto, Cuartero, Andres, de Paz, Concha, Cura, Isabel del, Jesus del Yerro, Maria, Diaz, Domingo, Domingo, Jose Luis, Emparanza, Jose I., Espallargues, Mireia, Espuga, Meritxell, Estevan, Patricia, Fernandez, M. Isabel, Ferrer, Montse, Ferreres, Yolanda, Fico, Giovanna, Forjaz, M. Joao, Barranco, Rosa Garcia, Garcia TorrecillasC Garcia-Ribera, J. Manuel, Garrido, Araceli, Gil, Elisa, Gomez, Marta, Gomez, Javier, Pinto, Ana Gonzalez, Haro, Josep Maria, Hernando, Margarita, Insigna, Maria Giola, Iriberri, Milagros, Jimenez, Nuria, Jimenez, Xavi, Larrauri, Amparo, Leon, Fernando, Lopez-Fresneña, Nieves, Lopez, Carmen, Lopez-Atanes Juan Antonio Lopez-Rodriguez, Mayte, Lopez-Cortacans, German, Martin, Jesus, Martinez-Cortés, Mercedes, Martinez-Martinez, Raquel, Martinez de Salazar, Alma D., Martinez, Isabel, Marzola, Marco, Mata, Nelva, Molina, Josep Maria, de Dios Molina, Juan, Molinero, Emilia, Mortier, Philippe, Muñoz, Carmen, Murru, Andrea, Olmedo, Jorge, Ortí, Rafael M., Padrós, Rafael, Pallejà, Meritxell, Parra, Raul, Pascual, Julio, Pelayo, Jose Maria, Pla, Rosa, Plana, Nieves, Aznar, Coro Perez, Gomez, Beatriz Perez, Zapata, Aurora Perez, Pijoan, Jose Ignacio, Polentinos, Elena, Puertolas, Beatriz, Puig, Maria Teresa, Quílez, Alex, Quintana, M. Jesus, Quiroga, Antonio, Rentero, David, Rey, Cristina, Rius, Cristina, Rodriguez-Blazquez, Carmen, Rojas, M. Jose, Romero, Yamina, Rubio, Gabriel, Rumayor, Mercedes, Ruiz, Pedro, Saenz, Margarita, Sanchez, Jesus, Sanchez-Arcilla, Ignacio, Sanz, Ferran, Serra, Consol, Serra-Sutton, Victoria, Serrano, Manuela, Sola, Silvia, Solera, Sara, Soto, Miguel, Tarrago, Alejandra, Tolosa, Natividad, Vazquez, Mireia, Viciola, Margarita, Vieta, Eduard, Vilagut, Gemma, Yago, Sara, Yañez, Jesus, Zapico, Yolanda, Zorita, Luis Maria, Zorrilla, Iñaki, Zurbano, Saioa L., Perez-Solá, Victor, Pelayo Terán, J.M, Fernández Villa, Tania, Marcos Delgado, Alba, and Martín Sánchez, Vicente

Abstract

[EN] Healthcare workers (HCW) are at high risk for suicide, yet little is known about the onset of suicidal thoughts and behaviors (STB) in this important segment of the population in conjunction with the COVID-19 pandemic. We conducted a multicenter, prospective cohort study of Spanish HCW active during the COVID-9 pandemic. A total of n = 4809 HCW participated at baseline (May–September 2020; i.e., just after the first wave of the pandemic) and at a four-month follow-up assessment (October–December 2020) using web-based surveys. Logistic regression assessed the individual- and population-level associations of separate proximal (pandemic) risk factors with four-month STB incidence (i.e., 30-day STB among HCW negative for 30-day STB at baseline), each time adjusting for distal (pre-pandemic) factors. STB incidence was estimated at 4.2% (SE = 0.5; n = 1 suicide attempt). Adjusted for distal factors, proximal risk factors most strongly associated with STB incidence were various sources of interpersonal stress (scaled 0–4; odds ratio [OR] range = 1.23–1.57) followed by personal health-related stress and stress related to the health of loved ones (scaled 0–4; OR range 1.30–1.32), and the perceived lack of healthcare center preparedness (scaled 0–4; OR = 1.34). Population-attributable risk proportions for these proximal risk factors were in the range 45.3–57.6%. Other significant risk factors were financial stressors (OR range 1.26–1.81), isolation/quarantine due to COVID-19 (OR = 1.53) and having changed to a specific COVID-19 related work location (OR = 1.72). Among other interventions, our findings call for healthcare systems to implement adequate conflict communication and resolution strategies and to improve family-work balance embedded in organizational justice strategies.

32. Improving data and knowledge management to better integrate health care and research

Author

Cases, Montserrat, Furlong, Laura I., Albanell, Joan, Altman, Russ B., Bellazzi, Riccardo, Boyer, Scott, Brand, Angela, Brookes, Anthony J., Brunak, Soren, Clark, Timothy W., Gea, Joaquim, Ghazal, Peter, Graf, Norbert, Guigo, Roderic, Klein, Teri E., Lopez-Bigas, Nuria, Maojo, Victor, Mons, Barend, Musen, Mark, Oliveira, José L., Rowe, Anthony, Ruch, Patrick, Shabo, Amnon, Shortliffe, Edward H., Valencia, Alfonso, van der Lei, Johan, Mayer, Miguel A., Sanz, Ferran, Cases, Montserrat, Furlong, Laura I., Albanell, Joan, Altman, Russ B., Bellazzi, Riccardo, Boyer, Scott, Brand, Angela, Brookes, Anthony J., Brunak, Soren, Clark, Timothy W., Gea, Joaquim, Ghazal, Peter, Graf, Norbert, Guigo, Roderic, Klein, Teri E., Lopez-Bigas, Nuria, Maojo, Victor, Mons, Barend, Musen, Mark, Oliveira, José L., Rowe, Anthony, Ruch, Patrick, Shabo, Amnon, Shortliffe, Edward H., Valencia, Alfonso, van der Lei, Johan, Mayer, Miguel A., and Sanz, Ferran

Abstract

Medicine is an increasingly data intensive discipline, with a growing need to link individual patient health records to rapidly changing research knowledge for better differential diagnosis, prognosis, and prediction of treatment response. Equally, biomedical research will gain massively from the integrative analysis of clinical and multi-omics information. Capitalizing on these opportunities must be guided by a precise understanding of many complex issues related to the integration of large amounts of diverse information. Partly this involves overcoming barriers between different disciplines, such as biology, medicine and computer sciences – implying a key role for ‘knowledge engineers’. This paper summarizes recent expert debates on such matters, leading to suggestions for concrete actions that should improve and better synergize both research and healthcare.

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