452 results on '"Calvas, P"'
Search Results
2. Deletion upstream of MAB21L2 highlights the importance of evolutionarily conserved non-coding sequences for eye development
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Fabiola Ceroni, Munevver B. Cicekdal, Richard Holt, Elena Sorokina, Nicolas Chassaing, Samuel Clokie, Thomas Naert, Lidiya V. Talbot, Sanaa Muheisen, Dorine A. Bax, Yesim Kesim, Emma C. Kivuva, Catherine Vincent-Delorme, Soeren S. Lienkamp, Julie Plaisancié, Elfride De Baere, Patrick Calvas, Kris Vleminckx, Elena V. Semina, and Nicola K. Ragge
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Science - Abstract
Abstract Anophthalmia, microphthalmia and coloboma (AMC) comprise a spectrum of developmental eye disorders, accounting for approximately 20% of childhood visual impairment. While non-coding regulatory sequences are increasingly recognised as contributing to disease burden, characterising their impact on gene function and phenotype remains challenging. Furthermore, little is known of the nature and extent of their contribution to AMC phenotypes. We report two families with variants in or near MAB21L2, a gene where genetic variants are known to cause AMC in humans and animal models. The first proband, presenting with microphthalmia and coloboma, has a likely pathogenic missense variant (c.338 G > C; p.[Trp113Ser]), segregating within the family. The second individual, presenting with microphthalmia, carries an ~ 113.5 kb homozygous deletion 19.38 kb upstream of MAB21L2. Modelling of the deletion results in transient small lens and coloboma as well as midbrain anomalies in zebrafish, and microphthalmia and coloboma in Xenopus tropicalis. Using conservation analysis, we identify 15 non-coding conserved elements (CEs) within the deleted region, while ChIP-seq data from mouse embryonic stem cells demonstrates that two of these (CE13 and 14) bind Otx2, a protein with an established role in eye development. Targeted disruption of CE14 in Xenopus tropicalis recapitulates an ocular coloboma phenotype, supporting its role in eye development. Together, our data provides insights into regulatory mechanisms underlying eye development and highlights the importance of non-coding sequences as a source of genetic diagnoses in AMC.
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- 2024
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3. Clinical and functional heterogeneity associated with the disruption of retinoic acid receptor beta
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Caron, Véronique, Chassaing, Nicolas, Ragge, Nicola, Boschann, Felix, Ngu, Angelina My-Hoa, Meloche, Elisabeth, Chorfi, Sarah, Lakhani, Saquib A, Ji, Weizhen, Steiner, Laurie, Marcadier, Julien, Jansen, Philip R, van de Pol, Laura A, van Hagen, Johanna M, Russi, Alvaro Serrano, Le Guyader, Gwenaël, Nordenskjöld, Magnus, Nordgren, Ann, Anderlid, Britt-Marie, Plaisancié, Julie, Stoltenburg, Corinna, Horn, Denise, Drenckhahn, Anne, Hamdan, Fadi F, Lefebvre, Mathilde, Attie-Bitach, Tania, Forey, Peggy, Smirnov, Vasily, Ernould, Françoise, Jacquemont, Marie-Line, Grotto, Sarah, Alcantud, Alberto, Coret, Alicia, Ferrer-Avargues, Rosario, Srivastava, Siddharth, Vincent-Delorme, Catherine, Romoser, Shelby, Safina, Nicole, Saade, Dimah, Lupski, James R, Calame, Daniel G, Geneviève, David, Chatron, Nicolas, Schluth-Bolard, Caroline, Myers, Kenneth A, Dobyns, William B, Calvas, Patrick, Study, The DDD, Salmon, Caroline, Holt, Richard, Elmslie, Frances, Allaire, Marc, Prigozhin, Daniil M, Tremblay, André, and Michaud, Jacques L
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Biological Sciences ,Genetics ,Clinical Research ,Pediatric ,2.1 Biological and endogenous factors ,Aetiology ,Humans ,Receptors ,Retinoic Acid ,Retinoids ,Microphthalmos ,DDD Study ,Dystonia ,Global developmental delay ,Microphthalmia ,Retinoic acid ,Retinoic acid receptor beta ,Clinical Sciences ,Genetics & Heredity - Abstract
PurposeDominant variants in the retinoic acid receptor beta (RARB) gene underlie a syndromic form of microphthalmia, known as MCOPS12, which is associated with other birth anomalies and global developmental delay with spasticity and/or dystonia. Here, we report 25 affected individuals with 17 novel pathogenic or likely pathogenic variants in RARB. This study aims to characterize the functional impact of these variants and describe the clinical spectrum of MCOPS12.MethodsWe used in vitro transcriptional assays and in silico structural analysis to assess the functional relevance of RARB variants in affecting the normal response to retinoids.ResultsWe found that all RARB variants tested in our assays exhibited either a gain-of-function or a loss-of-function activity. Loss-of-function variants disrupted RARB function through a dominant-negative effect, possibly by disrupting ligand binding and/or coactivators' recruitment. By reviewing clinical data from 52 affected individuals, we found that disruption of RARB is associated with a more variable phenotype than initially suspected, with the absence in some individuals of cardinal features of MCOPS12, such as developmental eye anomaly or motor impairment.ConclusionOur study indicates that pathogenic variants in RARB are functionally heterogeneous and associated with extensive clinical heterogeneity.
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- 2023
4. Large differences between observed and expected Ecuadorian deforestation from 2001 to 2009: a counterfactual simulation approach
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Calvas, Baltazar, Castro, Luz Maria, Kindu, Mengistie, Bingham, Logan, Pintado, Karla, Torres Celi, Jonathan, Knoke, Thomas, and Cueva-Ortiz, Jorge
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- 2024
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5. Clinical and genetic analysis further delineates the phenotypic spectrum of ALDH1A3-related anophthalmia and microphthalmia
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Kesim, Yesim, Ceroni, Fabiola, Damián, Alejandra, Blanco-Kelly, Fiona, Ayuso, Carmen, Williamson, Kathy, Paquis-Flucklinger, Véronique, Bax, Dorine A, Plaisancié, Julie, Rieubland, Claudine, Chamlal, Mostafa, Cortón, Marta, Chassaing, Nicolas, Calvas, Patrick, and Ragge, Nicola K
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- 2023
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6. Correction: Clinical and genetic analysis further delineates the phenotypic spectrum of ALDH1A3-related anophthalmia and microphthalmia
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Kesim, Yesim, Ceroni, Fabiola, Damián, Alejandra, Blanco-Kelly, Fiona, Ayuso, Carmen, Williamson, Kathy, Paquis-Flucklinger, Véronique, Bax, Dorine A, Plaisancié, Julie, Rieubland, Claudine, Chamlal, Mostafa, Cortón, Marta, Chassaing, Nicolas, Calvas, Patrick, and Ragge, Nicola K
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- 2023
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7. Evaluation of somatic and/or germline mosaicism in congenital malformation of the eye
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Chesneau, Bertrand, Ivashchenko, Véronique, Habib, Christophe, Gaston, Véronique, Escudié, Fréderic, Morel, Godelieve, Capri, Yline, Vincent-Delorme, Catherine, Calvas, Patrick, Chassaing, Nicolas, and Plaisancié, Julie
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- 2023
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8. Hoehn and Yahr Stage and Striatal Dat-SPECT Uptake Are Predictors of Parkinson’s Disease Motor Progression
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Jackson, Holly, Anzures-Cabrera, Judith, Taylor, Kirsten I, Pagano, Gennaro, Investigators, PASADENA, Group, Prasinezumab Study, Altendorf, Claudia, Anandan, Chareyna, Andrews, Giulia, Ansquer, Solène, Arrouasse, Raphaele, Aslam, Sana, Azulay, Jean-Philippe, Baker, Jeanette, Martinez, Ernest Balaguer, Barbu, Shadi, Bardram, Kara, Bega, Danny, Marco, Helena Bejr-Kasem, Benatru, Isabelle, Benchetrit, Eve, Bernhard, Felix, Besharat, Amir, Bette, Sagari, Bichon, Amelie, Billnitzer, Andrew, Blondeau, Sophie, Boraud, Thomas, Borngräber, Freiderike, Boyd, James, Brockmann, Kathrin, Brodsky, Matthew, Brown, Ethan, Bruecke, Christof, Calvas, Fabienne, Canelo, Monica, Carbone, Federico, Carroll, Claire, Fernandez, Laura Casado, Cassé-Perrot, Catherine, Castrioto, Anna, Catala, Helene, Chan, Justine, Cheriet, Samia, Ciabarra, Anthony, Classen, Joseph, Coleman, Juliana, Coleman, Robert, Compta, Yaroslau, Corbillé, Anne-Gaëlle, Corvol, Jean-Christophe, Cosgaya, Mariana, Dahodwala, Nabila, Damier, Philippe, David, Elodie, Davis, Thomas, Dean, Marissa, Debilly, Berengere, DeGiorgio, Janell, Deik, Andres, Delaby, Laure, Delfini, Marie-Helene, Derkinderen, Pascal, Derost, Philipp, de Toledo, Maria, Deuel, Lisa, Diaz-Hernandez, Ann Marie, Dietiker, Cameron, Dimenshteyn, Karina, Dotor, Julio, Durif, Franck, Ebentheuer, Jens, Eggert, Karla Maria, Madueño, Sara Eichau, Eickhoff, Claudia, Ellenbogen, Aaron, Ellmerer, Philipp, Vazquez, Ines Esparragosa, Eusebio, Alexandre, Ewert, Siobhan, Fang, John, Feigenbaum, Danielle, Fluchere, Frederique, Foubert-Samier, Alexandra, Fournier, Marie, Fradet, Anne, Fraix, Valerie, Frank, Samuel, Fries, Franca, Galitzky, Monique, Pérez, Marisol Gallardó, Moreno, Jose Manuel García, Gasca, Carmen, Gasser, Thomas, Gibbons, Joyce, Giordana, Caroline, Martinez, Alicia Gonzalez, Goodman, Ira, Gorospe, Arantza, and Goubeaud, Marie
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Biomedical and Clinical Sciences ,Clinical Sciences ,Psychology ,Biomedical Imaging ,Parkinson's Disease ,Brain Disorders ,Clinical Research ,Aging ,Neurosciences ,Neurodegenerative ,Clinical Trials and Supportive Activities ,Neurological ,PASADENA Investigators ,Prasinezumab Study Group ,Dat-SPECT imaging ,MDS-UPDRS ,PASADENA ,PPMI ,Parkinson’s disease ,disease stage ,progression predictors ,ridge regression ,Cognitive Sciences ,Biological psychology - Abstract
Currently, no treatments available for Parkinson's disease (PD) can slow PD progression. At the early stage of the disease, only a subset of individuals with PD progress quickly, while the majority have a slowly progressive form of the disease. In developing treatments that aim to slow PD progression, clinical trials aim to include individuals who are likely to progress faster, such that a treatment effect, if one exists, can be identified easier and earlier. The aim of the present study was to identify baseline predictors of clinical progression in early PD. We analyzed 12-month data acquired from the PASADENA trial Part 1 (NCT03100149, n = 76 participants who were allocated to the placebo arm and did not start symptomatic therapy) and the Parkinson's Progression Markers Initiative (PPMI) study (n = 139 demographically and clinically matched participants). By using ridge regression models including clinical characteristics, imaging, and non-imaging biomarkers, we found that Hoehn and Yahr stage and dopamine transporter single-photon emission computed tomography specific binding ratios (Dat-SPECT SBR) in putamen ipsilateral to the side of motor symptom onset predicted PD progression at the early stage of the disease. Further studies are needed to confirm the validity of these predictors to identify with high accuracy individuals with early PD with a faster progression phenotype.
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- 2021
9. A Phase II Study to Evaluate the Safety and Efficacy of Prasinezumab in Early Parkinson's Disease (PASADENA): Rationale, Design, and Baseline Data
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Pagano, Gennaro, Boess, Frank G, Taylor, Kirsten I, Ricci, Benedicte, Mollenhauer, Brit, Poewe, Werner, Boulay, Anne, Anzures-Cabrera, Judith, Vogt, Annamarie, Marchesi, Maddalena, Post, Anke, Nikolcheva, Tania, Kinney, Gene G, Zago, Wagner M, Ness, Daniel K, Svoboda, Hanno, Britschgi, Markus, Ostrowitzki, Susanne, Simuni, Tanya, Marek, Kenneth, Koller, Martin, Sevigny, Jeff, Doody, Rachelle, Fontoura, Paulo, Umbricht, Daniel, Bonni, Azad, Investigators, PASADENA, Group, Prasinezumab Study, Altendorf, Claudia, Anandan, Chareyna, Andrews, Giulia, Ansquer, Solène, Arrouasse, Raphaele, Aslam, Sana, Azulay, Jean-Philippe, Baker, Jeanette, Martinez, Ernest Balaguer, Barbu, Shadi, Bardram, Kara, Bega, Danny, Marco, Helena Bejr-Kasem, Benatru, Isabelle, Benchetrit, Eve, Bernhard, Felix, Besharat, Amir, Bette, Sagari, Bichon, Amelie, Billnitzer, Andrew, Blondeau, Sophie, Boraud, Thomas, Borngräber, Freiderike, Boyd, James, Brockmann, Kathrin, Brodsky, Matthew, Brown, Ethan, Bruecke, Christof, Calvas, Fabienne, Canelo, Monica, Carbone, Federico, Carroll, Claire, Fernandez, Laura Casado, Cassé-Perrot, Catherine, Castrioto, Anna, Catala, Helene, Chan, Justine, Cheriet, Samia, Ciabarra, Anthony, Classen, Joseph, Coleman, Juliana, Coleman, Robert, Compta, Yaroslau, Corbillé, Anne-Gaëlle, Corvol, Jean-Christophe, Cosgaya, Mariana, Dahodwala, Nabila, Damier, Philippe, David, Elodie, Davis, Thomas, Dean, Marissa, Debilly, Berengere, DeGiorgio, Janell, Deik, Andres, Delaby, Laure, Delfini, Marie-Helene, Derkinderen, Pascal, Derost, Philipp, de Toledo, Maria, Deuel, Lisa, Diaz-Hernandez, Ann Marie, Dietiker, Cameron, Dimenshteyn, Karina, Dotor, Julio, Durif, Franck, Ebentheuer, Jens, Eggert, Karla Maria, Madueño, Sara Eichau, Eickhoff, Claudia, Ellenbogen, Aaron, Ellmerer, Philipp, and Vazquez, Ines Esparragosa
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Biomedical and Clinical Sciences ,Clinical Sciences ,Neurodegenerative ,Parkinson's Disease ,Clinical Research ,Neurosciences ,Aging ,Clinical Trials and Supportive Activities ,Brain Disorders ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Neurological ,PASADENA Investigators ,Prasinezumab Study Group ,MDS-UPDRS = Movement Disorder Society—Unified Parkinson's Disease Rating Scale ,Parkinson's disease ,Phase II clinical trial ,alpha-synuclein ,disease modification treatments ,disease progression ,monoclonal antibodies ,prasinezumab ,Psychology ,Clinical sciences ,Biological psychology - Abstract
Background: Currently available treatments for Parkinson's disease (PD) do not slow clinical progression nor target alpha-synuclein, a key protein associated with the disease. Objective: The study objective was to evaluate the efficacy and safety of prasinezumab, a humanized monoclonal antibody that binds aggregated alpha-synuclein, in individuals with early PD. Methods: The PASADENA study is a multicenter, randomized, double-blind, placebo-controlled treatment study. Individuals with early PD, recruited across the US and Europe, received monthly intravenous doses of prasinezumab (1,500 or 4,500 mg) or placebo for a 52-week period (Part 1), followed by a 52-week extension (Part 2) in which all participants received active treatment. Key inclusion criteria were: aged 40-80 years; Hoehn & Yahr (H&Y) Stage I or II; time from diagnosis ≤2 years; having bradykinesia plus one other cardinal sign of PD (e.g., resting tremor, rigidity); DAT-SPECT imaging consistent with PD; and either treatment naïve or on a stable monoamine oxidase B (MAO-B) inhibitor dose. Study design assumptions for sample size and study duration were built using a patient cohort from the Parkinson's Progression Marker Initiative (PPMI). In this report, baseline characteristics are compared between the treatment-naïve and MAO-B inhibitor-treated PASADENA cohorts and between the PASADENA and PPMI populations. Results: Of the 443 patients screened, 316 were enrolled into the PASADENA study between June 2017 and November 2018, with an average age of 59.9 years and 67.4% being male. Mean time from diagnosis at baseline was 10.11 months, with 75.3% in H&Y Stage II. Baseline motor and non-motor symptoms (assessed using Movement Disorder Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS]) were similar in severity between the MAO-B inhibitor-treated and treatment-naïve PASADENA cohorts (MDS-UPDRS sum of Parts I + II + III [standard deviation (SD)]; 30.21 [11.96], 32.10 [13.20], respectively). The overall PASADENA population (63.6% treatment naïve and 36.4% on MAO-B inhibitor) showed a similar severity in MDS-UPDRS scores (e.g., MDS-UPDRS sum of Parts I + II + III [SD]; 31.41 [12.78], 32.63 [13.04], respectively) to the PPMI cohort (all treatment naïve). Conclusions: The PASADENA study population is suitable to investigate the potential of prasinezumab to slow disease progression in individuals with early PD. Trial Registration: NCT03100149.
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- 2021
10. GM2 gangliosidosis AB variant: first case of late onset and review of the literature
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Ganne, Benjamin, Dauriat, Benjamin, Richard, Laurence, Lamari, Foudil, Ghorab, Karima, Magy, Laurent, Benkirane, Mehdi, Perani, Alexandre, Marquet, Valentine, Calvas, Patrick, Yardin, Catherine, and Bourthoumieu, Sylvie
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- 2022
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11. Confronting sustainable intensification with uncertainty and extreme values on smallholder tropical farms
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Knoke, Thomas, Gosling, Elizabeth, Reith, Esther, Gerique, Andres, Pohle, Perdita, Valle Carrión, Liz, Ochoa Moreno, Wilman Santiago, Castro, Luz Maria, Calvas, Baltazar, Hildebrandt, Patrick, Döllerer, Martin, Bastit, Félix, and Paul, Carola
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- 2022
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12. Noninvasive prenatal diagnosis of genetic diseases induced by triplet repeat expansion by linked read haplotyping and Bayesian approach
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C. Liautard-Haag, G. Durif, C. VanGoethem, D. Baux, A. Louis, L. Cayrefourcq, M. Lamairia, M. Willems, C. Zordan, V. Dorian, C. Rooryck, C. Goizet, A. Chaussenot, L. Monteil, P. Calvas, C. Miry, R. Favre, E. Le Boette, M. Fradin, A. F. Roux, M. Cossée, M. Koenig, C. Alix-Panabière, C. Guissart, and M. C. Vincent
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Medicine ,Science - Abstract
Abstract The field of noninvasive prenatal diagnosis (NIPD) has undergone significant progress over the last decade. Direct haplotyping has been successfully applied for NIPD of few single-gene disorders. However, technical issues remain for triplet-repeat expansions. The objective of this study was to develop an NIPD approach for couples at risk of transmitting dynamic mutations. This method includes targeted enrichment for linked-read libraries and targeted maternal plasma DNA sequencing. We also developed an innovative Bayesian procedure to integrate the Hoobari fetal genotyping model for inferring the fetal haplotype and the targeted gene variant status. Our method of directly resolving parental haplotypes through targeted linked-read sequencing was smoothly performed using blood samples from families with Huntington’s disease or myotonic dystrophy type 1. The Bayesian analysis of transmission of parental haplotypes allowed defining the genotype of five fetuses. The predicted variant status of four of these fetuses was in agreement with the invasive prenatal diagnosis findings. Conversely, no conclusive result was obtained for the NIPD of fragile X syndrome. Although improvements should be made to achieve clinically acceptable accuracy, our study shows that linked-read sequencing and parental haplotype phasing can be successfully used for NIPD of triplet-repeat expansion diseases. Trial registration: NCT04698551_date of first registration: 07/01/2021.
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- 2022
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13. Noninvasive prenatal diagnosis of genetic diseases induced by triplet repeat expansion by linked read haplotyping and Bayesian approach
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Liautard-Haag, C., Durif, G., VanGoethem, C., Baux, D., Louis, A., Cayrefourcq, L., Lamairia, M., Willems, M., Zordan, C., Dorian, V., Rooryck, C., Goizet, C., Chaussenot, A., Monteil, L., Calvas, P., Miry, C., Favre, R., Le Boette, E., Fradin, M., Roux, A. F., Cossée, M., Koenig, M., Alix-Panabière, C., Guissart, C., and Vincent, M. C.
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- 2022
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14. Correction to: Evaluation of somatic and/or germline mosaicism in congenital malformation of the eye
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Chesneau, Bertrand, Ivashchenko, Véronique, Habib, Christophe, Gaston, Véronique, Escudié, Fréderic, Morel, Godelieve, Capri, Yline, Vincent-Delorme, Catherine, Calvas, Patrick, Chassaing, Nicolas, and Plaisancié, Julie
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- 2023
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15. Reformas curriculares en el área de Ciencias Sociales de la Educación Básica Superior en Ecuador
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María Gabriela Calvas Ojeda
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Reforma curricular, Educación Básica Superior, Histórico Local, Ciencias Sociales ,Education (General) ,L7-991 ,Social sciences (General) ,H1-99 - Abstract
Este artículo responde a un estudio descriptivo sobre las reformas curriculares implementadas en el subnivel Superior de la Educación General Básica en el campo de las Ciencias Sociales, tiene como objetivo analizar las propuestas curriculares del Ministerio de Educación de Ecuador entre los años 2010 a 2016, así como su alcance a la revalorización de la Historia Local en Décimo Grado. En el estudio fueron empleados los métodos de revisión bibliográfica, análisis documental, hermenéutico histórico-lógico y analítico-sintético. Entre los principales hallazgos destacan, la incorporación al currículo de aspectos del contexto, en el que se involucra el respeto por los saberes ancestrales, el rescate de fábulas, leyendas tradicionales y cuentos conservados mediante la transmisión de generación en generación por medio de la oralidad. También, se ofrecen reflexiones sobre los aportes de estos al proceso educativo.
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- 2022
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16. Liberté et autonomie à l’épreuve de la pandémie : quand protéger conduit à confiner (1) et quand libérer conduit à surveiller (2)
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Calvas, P.
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- 2020
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17. Re-focusing on Agnathia-Otocephaly complex
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Dubucs, C., Chassaing, N., Sergi, C., Aubert-Mucca, M., Attié-Bitach, T., Lacombe, D., Thauvin-Robinet, C., Arpin, S., Perez, M. J., Cabrol, C., Chen, C. P., Aziza, J., Colin, E., Martinovic, J., Calvas, P., and Plaisancié, Julie
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- 2021
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18. Confirmation of FZD5 implication in a cohort of 50 patients with ocular coloboma
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Aubert-Mucca, Marion, Pernin-Grandjean, Julie, Marchasson, Sébastien, Gaston, Veronique, Habib, Christophe, Meunier, Isabelle, Sigaudy, Sabine, Kaplan, Josseline, Roche, Olivier, Denis, Danièle, Bitoun, Pierre, Haye, Damien, Verloes, Alain, Calvas, Patrick, Chassaing, Nicolas, and Plaisancié, Julie
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- 2021
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19. Novel PXDN biallelic variants in patients with microphthalmia and anterior segment dysgenesis
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Zazo-Seco, Celia, Plaisancié, Julie, Bitoun, Pierre, Corton, Marta, Arteche, Ana, Ayuso, Carmen, Schneider, Adele, Zafeiropoulou, Dimitra, Gilissen, Christian, Roche, Olivier, Frémont, Felix, Calvas, Patrick, Slavotinek, Anne, Ragge, Nicola, and Chassaing, Nicolas
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- 2020
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20. Recurrent heterozygous PAX6 missense variants cause severe bilateral microphthalmia via predictable effects on DNA–protein interaction
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Williamson, Kathleen A., Hall, H. Nikki, Owen, Liusaidh J., Livesey, Benjamin J., Hanson, Isabel M., Adams, G. G. W., Bodek, Simon, Calvas, Patrick, Castle, Bruce, Clarke, Michael, Deng, Alexander T., Edery, Patrick, Fisher, Richard, Gillessen-Kaesbach, Gabriele, Heon, Elise, Hurst, Jane, Josifova, Dragana, Lorenz, Birgit, McKee, Shane, Meire, Francoise, Moore, Anthony T., Parker, Michael, Reiff, Charlotte M., Self, Jay, Tobias, Edward S., Verheij, Joke B. G. M., Willems, Marjolaine, Williams, Denise, van Heyningen, Veronica, Marsh, Joseph A., and FitzPatrick, David R.
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- 2020
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21. ATP8A2-related disorders as recessive cerebellar ataxia
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Guissart, Claire, Harrison, Alexander N., Benkirane, Mehdi, Oncel, Ibrahim, Arslan, Elif Acar, Chassevent, Anna K ., Baraῆano, Kristin, Larrieu, Lise, Iascone, Maria, Tenconi, Romano, Claustres, Mireille, Eroglu-Ertugrul, Nesibe, Calvas, Patrick, Topaloglu, Haluk, Molday, Robert S., and Koenig, Michel
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- 2020
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22. Hoehn and Yahr Stage and Striatal Dat-SPECT Uptake Are Predictors of Parkinson’s Disease Motor Progression
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Holly Jackson, Judith Anzures-Cabrera, Kirsten I. Taylor, Gennaro Pagano, PASADENA Investigators, Prasinezumab Study Group, Claudia Altendorf, Chareyna Anandan, Giulia Andrews, Solène Ansquer, Raphaele Arrouasse, Sana Aslam, Jean-Philippe Azulay, Jeanette Baker, Ernest Balaguer Martinez, Shadi Barbu, Kara Bardram, Danny Bega, Helena Bejr-Kasem Marco, Isabelle Benatru, Eve Benchetrit, Felix Bernhard, Amir Besharat, Sagari Bette, Amelie Bichon, Andrew Billnitzer, Sophie Blondeau, Thomas Boraud, Freiderike Borngräber, James Boyd, Kathrin Brockmann, Matthew Brodsky, Ethan Brown, Christof Bruecke, Fabienne Calvas, Monica Canelo, Federico Carbone, Claire Carroll, Laura Casado Fernandez, Catherine Cassé-Perrot, Anna Castrioto, Helene Catala, Justine Chan, Samia Cheriet, Anthony Ciabarra, Joseph Classen, Juliana Coleman, Robert Coleman, Yaroslau Compta, Anne-Gaëlle Corbillé, Jean-Christophe Corvol, Mariana Cosgaya, Nabila Dahodwala, Philippe Damier, Elodie David, Thomas Davis, Marissa Dean, Berengere Debilly, Janell DeGiorgio, Andres Deik, Laure Delaby, Marie-Helene Delfini, Pascal Derkinderen, Philipp Derost, Maria de Toledo, Lisa Deuel, Ann Marie Diaz-Hernandez, Cameron Dietiker, Karina Dimenshteyn, Julio Dotor, Franck Durif, Jens Ebentheuer, Karla Maria Eggert, Sara Eichau Madueño, Claudia Eickhoff, Aaron Ellenbogen, Philipp Ellmerer, Ines Esparragosa Vazquez, Alexandre Eusebio, Siobhan Ewert, John Fang, Danielle Feigenbaum, Frederique Fluchere, Alexandra Foubert-Samier, Marie Fournier, Anne Fradet, Valerie Fraix, Samuel Frank, Franca Fries, Monique Galitzky, Marisol Gallardó Pérez, Jose Manuel García Moreno, Carmen Gasca, Thomas Gasser, Joyce Gibbons, Caroline Giordana, Alicia Gonzalez Martinez, Ira Goodman, Arantza Gorospe, Marie Goubeaud, David Grabli, Mangone Graziella, Stephan Grimaldi, Jeffrey Gross, Raquel Guimaraes-Costa, Andreas Hartmann, Christian Hartmann, Travis Hassell, Robert Hauser, Antonio Hernandez, Jorge Hernandez-Vara, Guenter Hoeglinger, Christian Homedes, Andrea Horta-Barba, Jean-Luc Houeto, Julius Huebl, Jennifer Hui, Stuart Isaacson, Joseph Jankovic, Annette Janzen, Junior Jauregui, Jocelyne Jiao, Maria Jose Marti Domenech, Xavier Joseph, Srinath Kadimi, Pat Kaminski, Silja Kannenberg, Jan Kassubek, Maya Katz, Kevin Klos, Shannon Klos, Christopher Kobet, Jennifer Koebert, Patricia Krause, Andrea Kuehn, Jaime Kulisevsky Bojarsky, Rajeev Kumar, Martin Kunz, Lille Kurvits, Kimberly Kwei, Simon Laganiere, Brice Laurens, Johannes Levin, Oren Levy, Peter LeWitt, Gurutz Linazasoro Cristóbal, Irene Litvan, Karlo Lizarraga, Katherine Longardner, Rocio Lopez, Lydia Lopez Manzanares, Sara Lucas del Pozo, Maria Rosario Luquin Puido, Nijee Luthra, Kelly Lyons, Sylvia Maass, Gerrit Machetanz, Yolanda Macias, David Maltete, Jorge Uriel Manez Miro, Louise-Laure Mariani, Juan Marin, Kathrin Marini, Ana Marques, Gloria Marti, Saul Martinez, Wassilios Meissner, Sara Meoni, Brit Mollenhauer, Dunia Mon Martinez, Johnson Moon, Elena Moro, Peter Morrison, Christoph Muehlberg, Manpreet Multani, Christine Murphy, Anthony Nicholas, Rajesh Pahwa, Antonio Palasi, Heidi Pape, Neepa Patel, Prity Patel, Marina Peball, Elizabeth Peckham, Terry Peery, Rafael Perez, Jesus Perez, Alisa Petit, Elmar Pinkhardt, Werner Poewe, Elsa Pomies, Cecile Preterre, Joseph Quinn, Olivier Rascol, Philippe Remy, Irene Richard, Benjamin Roeben, Emily Ruether, Jost-Julian Rumpf, David Russell, Hayet Salhi, Daniela Samaniego-Toro, Alexandra Samier-Foubert, Antonio Sanchez, Emmanuelle Schmitt, Alfons Schnitzler, Oliver Schorr, Julie Schwartzbard, Kerstin Schweyer, Klaus Seppi, Victoria Sergo, Holly Shill, Andrew Siderowf, Tanya Simuni, Umberto Spampinato, Ashok Sriram, Natividad Stover, Caroline Tanner, Arjun Tarakad, Carolyn Taylor, Claire Thalamus, Thomas Toothaker, Nadege Van Blercom, Nora Vanegas-Arrogave, Lydia Vela, Sylvian Vergnet, Tiphaine Vidal, Jonathan Vöglein, Ryan Walsh, Cheryl Waters, Mirko Wegscheider, Endy Weidinger, Caroline Weill, Gregor Wenzel, Tatiana Witjas, Isabel Wurster, Brenton Wright, Milan Zimmermann, Rafael Zuzuarregui, Markus Abt, Atieh Bamdadian, Teresa Barata, Nicholas Barbet, Sara Belli, Frank Boess, Azad Bonni, Edilio Borroni, Anne Boulay, Markus Britschgi, Jerome Chague, Valerie Cosson, Christian Czech, Dennis Deptula, Cheikh Diack, Rachelle Doody, Juergen Dukart, Giulia D’Urso, Sebastian Dziadek, Hannah Eddleston, Chris Edgar, Laurent Essioux, Morgan Farell, Rebecca Finch, Paulo Fontoura, Waltraud Gruenbauer, Andrea Hahn, Stefan Holiga, Michael Honer, Shirin Jadidi, Kelly Johnson-Wood, Markus Keller, Timothy Kilchenmann, Martin Koller, Thomas Kremer, Thomas Kustermann, Claire Landsdall, Michael Lindemann, Florian Lipsmeier, Cecile Luzy, Marianne Manchester, Maddalena Marchesi, Ferenc Martenyi, Meret Martin-Facklam, Katerina Mironova, Annabelle Monnet, Emma Moore, Daniel K Ness, Markus Niggli, Tania Nikolcheva, Susanne Ostrowitzki GP, Benedicte Passmard, Agnes Poirier, Anke Post, Megana Prasad, Nathalie Pross, Tiffany Quock, Benedicte Ricci, Ellen Rose, Christoph Sarry, Christine Schubert, Dennis Selkoe, Jeff Sevigny, Kaycee Sink, Hannah Staunton, Tim Steven, Alexander Strasak, Hanno Svoboda KT, Radhika Tripuraneni, Dylan Trundell, Daniel Umbricht, Lynne Verselis, Annamarie Vogt, Ekaterina Volkova-Volkmar, Cornelia Weber, Silke Weber, and Wagner Zago
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PASADENA ,PPMI (Parkinson’s Progression Markers Initiative) ,Parkinson’s disease ,progression predictors ,ridge regression ,disease stage ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Currently, no treatments available for Parkinson’s disease (PD) can slow PD progression. At the early stage of the disease, only a subset of individuals with PD progress quickly, while the majority have a slowly progressive form of the disease. In developing treatments that aim to slow PD progression, clinical trials aim to include individuals who are likely to progress faster, such that a treatment effect, if one exists, can be identified easier and earlier. The aim of the present study was to identify baseline predictors of clinical progression in early PD. We analyzed 12-month data acquired from the PASADENA trial Part 1 (NCT03100149, n = 76 participants who were allocated to the placebo arm and did not start symptomatic therapy) and the Parkinson’s Progression Markers Initiative (PPMI) study (n = 139 demographically and clinically matched participants). By using ridge regression models including clinical characteristics, imaging, and non-imaging biomarkers, we found that Hoehn and Yahr stage and dopamine transporter single-photon emission computed tomography specific binding ratios (Dat-SPECT SBR) in putamen ipsilateral to the side of motor symptom onset predicted PD progression at the early stage of the disease. Further studies are needed to confirm the validity of these predictors to identify with high accuracy individuals with early PD with a faster progression phenotype.
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- 2021
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23. A Phase II Study to Evaluate the Safety and Efficacy of Prasinezumab in Early Parkinson's Disease (PASADENA): Rationale, Design, and Baseline Data
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Gennaro Pagano, Frank G. Boess, Kirsten I. Taylor, Benedicte Ricci, Brit Mollenhauer, Werner Poewe, Anne Boulay, Judith Anzures-Cabrera, Annamarie Vogt, Maddalena Marchesi, Anke Post, Tania Nikolcheva, Gene G. Kinney, Wagner M. Zago, Daniel K. Ness, Hanno Svoboda, Markus Britschgi, Susanne Ostrowitzki, Tanya Simuni, Kenneth Marek, Martin Koller, Jeff Sevigny, Rachelle Doody, Paulo Fontoura, Daniel Umbricht, Azad Bonni, PASADENA Investigators, Prasinezumab Study Group, Claudia Altendorf, Chareyna Anandan, Giulia Andrews, Solène Ansquer, Raphaele Arrouasse, Sana Aslam, Jean-Philippe Azulay, Jeanette Baker, Ernest Balaguer Martinez, Shadi Barbu, Kara Bardram, Danny Bega, Helena Bejr-Kasem Marco, Isabelle Benatru, Eve Benchetrit, Felix Bernhard, Amir Besharat, Sagari Bette, Amelie Bichon, Andrew Billnitzer, Sophie Blondeau, Thomas Boraud, Freiderike Borngräber, James Boyd, Kathrin Brockmann, Matthew Brodsky, Ethan Brown, Christof Bruecke, Fabienne Calvas, Monica Canelo, Federico Carbone, Claire Carroll, Laura Casado Fernandez, Catherine Cassé-Perrot, Anna Castrioto, Helene Catala, Justine Chan, Samia Cheriet, Anthony Ciabarra, Joseph Classen, Juliana Coleman, Robert Coleman, Yaroslau Compta, Anne-Gaëlle Corbillé, Jean-Christophe Corvol, Mariana Cosgaya, Nabila Dahodwala, Philippe Damier, Elodie David, Thomas Davis, Marissa Dean, Berengere Debilly, Janell DeGiorgio, Andres Deik, Laure Delaby, Marie-Helene Delfini, Pascal Derkinderen, Philipp Derost, Maria de Toledo, Lisa Deuel, Ann Marie Diaz-Hernandez, Cameron Dietiker, Karina Dimenshteyn, Julio Dotor, Franck Durif, Jens Ebentheuer, Karla Maria Eggert, Sara Eichau Madueño, Claudia Eickhoff, Aaron Ellenbogen, Philipp Ellmerer, Ines Esparragosa Vazquez, Alexandre Eusebio, Siobhan Ewert, John Fang, Danielle Feigenbaum, Frederique Fluchere, Alexandra Foubert-Samier, Marie Fournier, Anne Fradet, Valerie Fraix, Samuel Frank, Franca Fries, Monique Galitzky, Marisol Gallardó Pérez, Jose Manuel García Moreno, Carmen Gasca, Thomas Gasser, Joyce Gibbons, Caroline Giordana, Alicia Gonzalez Martinez, Ira Goodman, Arantza Gorospe, Marie Goubeaud, David Grabli, Mangone Graziella, Stephan Grimaldi, Jeffrey Gross, Raquel Guimaraes-Costa, Andreas Hartmann, Christian Hartmann, Travis Hassell, Robert Hauser, Antonio Hernandez, Jorge Hernandez-Vara, Günter Höglinger, Christian Homedes, Andrea Horta-Barba, Jean-Luc Houeto, Julius Huebl, Jennifer Hui, Stuart Isaacson, Joseph Jankovic, Annette Janzen, Junior Jauregui, Jocelyne Jiao, Maria Jose Marti Domenech, Xavier Joseph, Srinath Kadimi, Pat Kaminski, Silja Kannenberg, Jan Kassubek, Maya Katz, Kevin Klos, Shannon Klos, Christopher Kobet, Jennifer Koebert, Patricia Krause, Andrea Kuehn, Jaime Kulisevsky Bojarsky, Rajeev Kumar, Martin Kunz, Lille Kurvits, Kimberly Kwei, Simon Laganiere, Brice Laurens, Johannes Levin, Oren Levy, Peter LeWitt, Gurutz Linazasoro Cristóbal, Irene Litvan, Karlo Lizarraga, Katherine Longardner, Rocio Lopez, Lydia Lopez Manzanares, Sara Lucas del Pozo, Maria Rosario Luquin Puido, Nijee Luthra, Kelly Lyons, Sylvia Maass, Gerrit Machetanz, Yolanda Macias, David Maltete, Jorge Uriel Manez Miro, Louise-Laure Mariani, Juan Marin, Kathrin Marini, Ana Marques, Gloria Marti, Saul Martinez, Wassilios Meissner, Sara Meoni, Dunia Mon Martinez, Johnson Moon, Elena Moro, Peter Morrison, Christoph Muehlberg, Manpreet Multani, Christine Murphy, Anthony Nicholas, Rajesh Pahwa, Antonio Palasi, Heidi Pape, Neepa Patel, Prity Patel, Marina Peball, Elizabeth Peckham, Terry Peery, Rafael Perez, Jesus Perez, Alisa Petit, Elmar Pinkhardt, Elsa Pomies, Cecile Preterre, Joseph Quinn, Olivier Rascol, Philippe Remy, Irene Richard, Benjamin Roeben, Emily Ruether, Jost-Julian Rumpf, David Russell, Hayet Salhi, Daniela Samaniego-Toro, Alexandra Samier-Foubert, Antonio Sanchez, Emmanuelle Schmitt, Alfons Schnitzler, Oliver Schorr, Julie Schwartzbard, Kerstin Schweyer, Klaus Seppi, Victoria Sergo, Holly Shill, Andrew Siderowf, Umberto Spampinato, Ashok Sriram, Natividad Stover, Caroline Tanner, Arjun Tarakad, Carolyn Taylor, Claire Thalamus, Thomas Toothaker, Nadege Van Blercom, Nora Vanegas-Arrogave, Lydia Vela, Sylvian Vergnet, Tiphaine Vidal, Jonathan Vöglein, Ryan Walsh, Cheryl Waters, Mirko Wegscheider, Endy Weidinger, Caroline Weill, Gregor Wenzel, Tatiana Witjas, Isabel Wurster, Brenton Wright, Milan Zimmermann, Rafael Zuzuarregui, Markus Abt, Atieh Bamdadian, Teresa Barata, Nicholas Barbet, Sara Belli, Frank Boess, Edilio Borroni, Jerome Chague, Valerie Cosson, Christian Czech, Dennis Deptula, Cheikh Diack, Juergen Dukart, Giulia D'Urso, Sebastian Dziadek, Hannah Eddleston, Chris Edgar, Laurent Essioux, Morgan Farell, Rebecca Finch, Waltraud Gruenbauer, Andrea Hahn, Stefan Holiga, Michael Honer, Shirin Jadidi, Kelly Johnson-Wood, Markus Keller, Timothy Kilchenmann, Thomas Kremer, Thomas Kustermann, Claire Landsdall, Michael Lindemann, Florian Lipsmeier, Cecile Luzy, Marianne Manchester, Ferenc Martenyi, Meret Martin-Facklam, Katerina Mironova, Annabelle Monnet, Emma Moore, Daniel K Ness, Markus Niggli, Benedicte Passmard, Agnes Poirier, Megana Prasad, Nathalie Pross, Tiffany Quock, Ellen Rose, Christoph Sarry, Christine Schubert, Dennis Selkoe, Kaycee Sink, Hannah Staunton, Tim Steven, Alexander Strasak, Kirsten Taylor, Radhika Tripuraneni, Dylan Trundell, Lynne Verselis, Ekaterina Volkova-Volkmar, Cornelia Weber, Silke Weber, and Wagner Zago
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Parkinson's disease ,alpha-synuclein (α-syn) ,prasinezumab ,monoclonal antibodies ,disease progression ,MDS-UPDRS = Movement Disorder Society—Unified Parkinson's Disease Rating Scale ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Background: Currently available treatments for Parkinson's disease (PD) do not slow clinical progression nor target alpha-synuclein, a key protein associated with the disease.Objective: The study objective was to evaluate the efficacy and safety of prasinezumab, a humanized monoclonal antibody that binds aggregated alpha-synuclein, in individuals with early PD.Methods: The PASADENA study is a multicenter, randomized, double-blind, placebo-controlled treatment study. Individuals with early PD, recruited across the US and Europe, received monthly intravenous doses of prasinezumab (1,500 or 4,500 mg) or placebo for a 52-week period (Part 1), followed by a 52-week extension (Part 2) in which all participants received active treatment. Key inclusion criteria were: aged 40–80 years; Hoehn & Yahr (H&Y) Stage I or II; time from diagnosis ≤2 years; having bradykinesia plus one other cardinal sign of PD (e.g., resting tremor, rigidity); DAT-SPECT imaging consistent with PD; and either treatment naïve or on a stable monoamine oxidase B (MAO-B) inhibitor dose. Study design assumptions for sample size and study duration were built using a patient cohort from the Parkinson's Progression Marker Initiative (PPMI). In this report, baseline characteristics are compared between the treatment-naïve and MAO-B inhibitor-treated PASADENA cohorts and between the PASADENA and PPMI populations.Results: Of the 443 patients screened, 316 were enrolled into the PASADENA study between June 2017 and November 2018, with an average age of 59.9 years and 67.4% being male. Mean time from diagnosis at baseline was 10.11 months, with 75.3% in H&Y Stage II. Baseline motor and non-motor symptoms (assessed using Movement Disorder Society—Unified Parkinson's Disease Rating Scale [MDS-UPDRS]) were similar in severity between the MAO-B inhibitor-treated and treatment-naïve PASADENA cohorts (MDS-UPDRS sum of Parts I + II + III [standard deviation (SD)]; 30.21 [11.96], 32.10 [13.20], respectively). The overall PASADENA population (63.6% treatment naïve and 36.4% on MAO-B inhibitor) showed a similar severity in MDS-UPDRS scores (e.g., MDS-UPDRS sum of Parts I + II + III [SD]; 31.41 [12.78], 32.63 [13.04], respectively) to the PPMI cohort (all treatment naïve).Conclusions: The PASADENA study population is suitable to investigate the potential of prasinezumab to slow disease progression in individuals with early PD.Trial Registration: NCT03100149.
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- 2021
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24. Outcomes of 4 years of molecular genetic diagnosis on a panel of genes involved in premature aging syndromes, including laminopathies and related disorders
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Maude Grelet, Véronique Blanck, Sabine Sigaudy, Nicole Philip, Fabienne Giuliano, Khaoula Khachnaoui, Godelieve Morel, Sarah Grotto, Julia Sophie, Céline Poirsier, James Lespinasse, Laurent Alric, Patrick Calvas, Gihane Chalhoub, Valérie Layet, Arnaud Molin, Cindy Colson, Luisa Marsili, Patrick Edery, Nicolas Lévy, and Annachiara De Sandre-Giovannoli
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Progeroid ,Panel ,Pathogenic,variant ,Medicine - Abstract
Abstract Background Segmental progeroid syndromes are a heterogeneous group of rare and often severe genetic disorders that have been studied since the twentieth century. These progeroid syndromes are defined as segmental because only some of the features observed during natural aging are accelerated. Methods Since 2015, the Molecular Genetics Laboratory in Marseille La Timone Hospital proposes molecular diagnosis of premature aging syndromes including laminopathies and related disorders upon NGS sequencing of a panel of 82 genes involved in these syndromes. We analyzed the results obtained in 4 years on 66 patients issued from France and abroad. Results Globally, pathogenic or likely pathogenic variants (ACMG class 5 or 4) were identified in about 1/4 of the cases; among these, 9 pathogenic variants were novel. On the other hand, the diagnostic yield of our panel was over 60% when the patients were addressed upon a nosologically specific clinical suspicion, excepted for connective tissue disorders, for which clinical diagnosis may be more challenging. Prenatal testing was proposed to 3 families. We additionally detected 16 variants of uncertain significance and reclassified 3 of them as benign upon segregation analysis in first degree relatives. Conclusions High throughput sequencing using the Laminopathies/ Premature Aging disorders panel allowed molecular diagnosis of rare disorders associated with premature aging features and genetic counseling for families, representing an interesting first-level analysis before whole genome sequencing may be proposed, as a future second step, by the National high throughput sequencing platforms (“Medicine France Genomics 2025” Plan), in families without molecular diagnosis.
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- 2019
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25. Fundamentos filosóficos de la historia local en las ciencias sociales educación básica superior
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María Gabriela Calvas Ojeda
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fundamentos de historia local ,enseñanza aprendizaje ,ciencias sociales ,Social Sciences ,Social sciences (General) ,H1-99 - Abstract
El artículo inicia con una aproximación descriptiva y conceptual de los fundamentos filosóficos de la historia local aplicada en el campo de las ciencias sociales, reflexiona acerca de su vinculación en el proceso de enseñanza aprendizaje de la Educación Básica Superior como actividad encaminada a la construcción social, histórica y cultural de los estudiantes del décimo grado. El objetivo del artículo es ofrecer una breve aproximación filosófica de la historia local y sus implicaciones en las ciencias sociales mediante la sistematización bibliográfica y análisis de textos, lo que facilito obtener resultados teóricos y por ende concluir que esta disciplina representa un proceso interdisciplinario en el currículo de las Ciencias Sociales, constituyendo no solo una poderosa herramienta para promover la identidad, capacidad investigativa e intercultural sino además de aprehensión en la práctica educativa.
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- 2019
26. LAS COMPETENCIAS PARA LA GESTIÓN CIENTÍFICO-PEDAGÓGICA DEL PROFESIONAL DE LA EDUCACIÓN
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Eudaldo Enrique Espinoza Freire, Gladys Narcisa Zúñiga Reyes, and María Gabriela Calvas Ojeda
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competencias, dirección, sistemas educativos, proceso de enseñanza-aprendizaje, desarrollo local ,Education - Abstract
Este trabajo responde a una investigación descriptiva, con el objetivo de analizar las competencias de dirección que deben caracterizar al director del siglo XXI, partiendo de los conocimientos y consideraciones que se manejan en la bibliografía especializada sobre dirección de los sistemas educativos. La estrategia metodológica se fundamenta en el método hermenéutico. Entre los principales hallazgos encontramos que las competencias del directivo educacional son definidas como los saberes y capacidades direccionados a la consecución del mejoramiento de los procesos que se llevan a cabo en las instituciones educativas, pedagógicos, académicos, administrativos y comunitarios. Los que se agrupan en cuatro grandes categorías: la gestión académica, la gestión directiva, la gestión administrativa y financiera, y la gestión comunitaria. La dirección educacional en los países de Latinoamérica demanda un director con liderazgo transformacional manifiesto a través de las dimensiones pedagógica, instructiva o para el aprendizaje; distribuida, participativa o colegiada y contextualizada o social que contribuya al desarrollo local.
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- 2019
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27. 4q25 microdeletion encompassing PITX2: A patient presenting with tetralogy of Fallot and dental anomalies without ocular features
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Vande Perre, P., Zazo Seco, C., Patat, O., Bouneau, L., Vigouroux, A., Bourgeois, D., El Hout, S., Chassaing, N., and Calvas, P.
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- 2018
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28. Searching for secondary findings: considering actionability and preserving the right not to know
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Isidor, Bertrand, Julia, Sophie, Saugier-Veber, Pascale, Weil-Dubuc, Paul-Loup, Bézieau, Stéphane, Bieth, Eric, Bonnefont, Jean-Paul, Munnich, Arnold, Bourdeaut, Franck, Bourgain, Catherine, Chassaing, Nicolas, Corradini, Nadège, Haye, Damien, Plaisancie, Julie, Dupin-Deguine, Delphine, Calvas, Patrick, Mignot, Cyril, Cogné, Benjamin, Manouvrier, Sylvie, Pasquier, Laurent, Héron, Delphine, Boycott, Kym M, Turrini, Mauro, Vears, Danya F., Nizon, Mathilde, and Vincent, Marie
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- 2019
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29. Expanding the phenotype of the X-linked BCOR microphthalmia syndromes
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Ragge, Nicola, Isidor, Bertrand, Bitoun, Pierre, Odent, Sylvie, Giurgea, Irina, Cogné, Benjamin, Deb, Wallid, Vincent, Marie, Le Gall, Jessica, Morton, Jenny, Lim, Derek, DDD Study, Le Meur, Guylène, Zazo Seco, Celia, Zafeiropoulou, Dimitra, Bax, Dorine, Zwijnenburg, Petra, Arteche, Anara, Swafiri, Saoud Tahsin, Cleaver, Ruth, McEntagart, Meriel, Kini, Usha, Newman, William, Ayuso, Carmen, Corton, Marta, Herenger, Yvan, Jeanne, Médéric, Calvas, Patrick, and Chassaing, Nicolas
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- 2019
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30. Through the looking glass: eye anomalies in the age of molecular science
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Calvas, Patrick, Traboulsi, Elias I., and Ragge, Nicola
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- 2019
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31. Genetics of anophthalmia and microphthalmia. Part 1: Non-syndromic anophthalmia/microphthalmia
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Plaisancié, J., Ceroni, F., Holt, R., Zazo Seco, C., Calvas, P., Chassaing, N., and Ragge, Nicola K.
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- 2019
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32. The curricular design by competences
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Daniela Estefanía Valarezo-Serrano, Francisco Israel Sare-Ochoa, and María Gabriela Calvas-Ojeda
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diseño ,curriculum ,competencias ,Education (General) ,L7-991 ,Special aspects of education ,LC8-6691 - Abstract
The objective of the present article consists on being able to investigate a positive answer about the importance of implementing the competitions inside the curricular plan as potentiate end the development that can achieve the educating inside the social context and in the educational environment and to meditate the complex competitions can be applied in the currículum for the development and strengths of the same one about how. With this purpose a consistent methodological strategy was used in the revision and bibliographical critic, as well as in the use of theoretical and empiric methods, besides technical and instruments like the interviews group and in depth, the participant observation and the application of questionnaires, what allowed to obtain derived theoretical results of the analysis and the author's experience and to arrive to the conclusions that finally are exposed.
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- 2018
33. Reflections on a strategy to teach geography in Basic Education of Ecuador
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Eudaldo Enrique Espinoza-Freire, María Gabriela Calvas-Ojeda, and Samuel Efraín Chuquirima-Espinoza
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situaciones de aprendizaje con mapas ,estrategia metodológica ,sistematicidad ,incapacidad estudiantil ,Education (General) ,L7-991 ,Special aspects of education ,LC8-6691 - Abstract
The research socializes experiences in learning situations, where the methodologies contribute to the effectiveness of the didactic with maps and the development of teaching-learning of geography. The objective was to review the ways of teaching Geography in the Basic Education of Passage, where it is possible to recognize problems related to the teaching performance through maps. The methodological strategy consisted in bibliographic systematization, text analysis, interpretative understanding and diagnosis of teaching situations, observation and the elaboration of a strategy, this methodical structure provides a vision of the work with maps.
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- 2018
34. Characterization of glycosylphosphatidylinositol biosynthesis defects by clinical features, flow cytometry, and automated image analysis
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Alexej Knaus, Jean Tori Pantel, Manuela Pendziwiat, Nurulhuda Hajjir, Max Zhao, Tzung-Chien Hsieh, Max Schubach, Yaron Gurovich, Nicole Fleischer, Marten Jäger, Sebastian Köhler, Hiltrud Muhle, Christian Korff, Rikke S. Møller, Allan Bayat, Patrick Calvas, Nicolas Chassaing, Hannah Warren, Steven Skinner, Raymond Louie, Christina Evers, Marc Bohn, Hans-Jürgen Christen, Myrthe van den Born, Ewa Obersztyn, Agnieszka Charzewska, Milda Endziniene, Fanny Kortüm, Natasha Brown, Peter N. Robinson, Helenius J. Schelhaas, Yvonne Weber, Ingo Helbig, Stefan Mundlos, Denise Horn, and Peter M. Krawitz
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GPI ,Anchor biosynthesis defects ,Automated image analysis ,Gene ,Prediction ,Medicine ,Genetics ,QH426-470 - Abstract
Abstract Background Glycosylphosphatidylinositol biosynthesis defects (GPIBDs) cause a group of phenotypically overlapping recessive syndromes with intellectual disability, for which pathogenic mutations have been described in 16 genes of the corresponding molecular pathway. An elevated serum activity of alkaline phosphatase (AP), a GPI-linked enzyme, has been used to assign GPIBDs to the phenotypic series of hyperphosphatasia with mental retardation syndrome (HPMRS) and to distinguish them from another subset of GPIBDs, termed multiple congenital anomalies hypotonia seizures syndrome (MCAHS). However, the increasing number of individuals with a GPIBD shows that hyperphosphatasia is a variable feature that is not ideal for a clinical classification. Methods We studied the discriminatory power of multiple GPI-linked substrates that were assessed by flow cytometry in blood cells and fibroblasts of 39 and 14 individuals with a GPIBD, respectively. On the phenotypic level, we evaluated the frequency of occurrence of clinical symptoms and analyzed the performance of computer-assisted image analysis of the facial gestalt in 91 individuals. Results We found that certain malformations such as Morbus Hirschsprung and diaphragmatic defects are more likely to be associated with particular gene defects (PIGV, PGAP3, PIGN). However, especially at the severe end of the clinical spectrum of HPMRS, there is a high phenotypic overlap with MCAHS. Elevation of AP has also been documented in some of the individuals with MCAHS, namely those with PIGA mutations. Although the impairment of GPI-linked substrates is supposed to play the key role in the pathophysiology of GPIBDs, we could not observe gene-specific profiles for flow cytometric markers or a correlation between their cell surface levels and the severity of the phenotype. In contrast, it was facial recognition software that achieved the highest accuracy in predicting the disease-causing gene in a GPIBD. Conclusions Due to the overlapping clinical spectrum of both HPMRS and MCAHS in the majority of affected individuals, the elevation of AP and the reduced surface levels of GPI-linked markers in both groups, a common classification as GPIBDs is recommended. The effectiveness of computer-assisted gestalt analysis for the correct gene inference in a GPIBD and probably beyond is remarkable and illustrates how the information contained in human faces is pivotal in the delineation of genetic entities.
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- 2018
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35. Single Circulating Fetal Trophoblastic Cells Eligible for Non Invasive Prenatal Diagnosis: the Exception Rather than the Rule
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Cayrefourcq, Laure, Vincent, Marie-Claire, Pierredon, Sandra, Moutou, Céline, Imbert-Bouteille, Marion, Haquet, Emmanuelle, Puechberty, Jacques, Willems, Marjolaine, Liautard-Haag, Cathy, Molinari, Nicolas, Zordan, Cécile, Dorian, Virginie, Rooryck-Thambo, Caroline, Goizet, Cyril, Chaussenot, Annabelle, Rouzier, Cécile, Boureau-Wirth, Amandine, Monteil, Laetitia, Calvas, Patrick, Miry, Claire, Favre, Romain, Petrov, Yuliya, Khau Van Kien, Philippe, Le Boette, Elsa, Fradin, Mélanie, Alix-Panabières, Catherine, and Guissart, Claire
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- 2020
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36. Implication of non-coding PAX6 mutations in aniridia
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Plaisancié, Julie, Tarilonte, M., Ramos, P., Jeanton-Scaramouche, C., Gaston, V., Dollfus, H., Aguilera, D., Kaplan, J., Fares-Taie, L., Blanco-Kelly, F., Villaverde, C., Francannet, C., Goldenberg, A., Arroyo, I., Rozet, J. M., Ayuso, C., Chassaing, N., Calvas, P., and Corton, M.
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- 2018
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37. Integrated bio-economic models as tools to support land-use decision making: a review of potential and limitations
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Castro, Luz Maria, Härtl, Fabian, Ochoa, Santiago, Calvas, Baltazar, Izquierdo, Leonardo, and Knoke, Thomas
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- 2018
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38. The teaching of history through histories
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María Gabriela Calvas-Ojeda and Enrique Espinoza-Freire
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Historia ,historietas ,recurso didáctico ,proceso de enseñanza-aprendizaje ,Education (General) ,L7-991 ,Special aspects of education ,LC8-6691 - Abstract
The comic strips have been introduced into the world of history as a didactic resource for their learning; However, there are still shortcomings in their use by teachers, motivated on many occasions due to lack of knowledge and insufficient methodological preparation; The purpose of this work is to socialize knowledge related to these didactic resources to contribute to the didactic-methodological enrichment of the teacher, in order to change this attitude. The methodological strategy responds to the quantitative-qualitative paradigm; in the collection of the information a participant observation guide was used to the history classes and interview to a sample of 9 teachers of Third Degree of the schools of the city of Machala randomly selected. We recorded the observations of the knowledge acquired by the 98 students who received the classes mediated by comic strips, which allowed us to conclude that comics for the teaching and learning of History constitute a powerful didactic resource.
- Published
- 2017
39. Exploring venlafaxine pharmacokinetic variability with a phenotyping approach, a multicentric french-swiss study (MARVEL study)
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Célia Lloret-Linares, Youssef Daali, Sylvie Chevret, Isabelle Nieto, Fanny Molière, Philippe Courtet, Florence Galtier, Raphaëlle-Marie Richieri, Sophie Morange, Pierre-Michel Llorca, Wissam El-Hage, Thomas Desmidt, Frédéric Haesebaert, Philippe Vignaud, Jerôme Holtzmann, Jean-Luc Cracowski, Marion Leboyer, Antoine Yrondi, Fabienne Calvas, Liova Yon, Philippe Le Corvoisier, Olivier Doumy, Kyle Heron, Damien Montange, Siamak Davani, Julien Déglon, Marie Besson, Jules Desmeules, Emmanuel Haffen, and Frank Bellivier
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Therapeutics. Pharmacology ,RM1-950 ,Toxicology. Poisons ,RA1190-1270 - Abstract
Abstract Background It is well known that the standard doses of a given drug may not have equivalent effects in all patients. To date, the management of depression remains mainly empirical and often poorly evaluated. The development of a personalized medicine in psychiatry may reduce treatment failure, intolerance or resistance, and hence the burden and costs of mood depressive disorders. The Geneva Cocktail Phenotypic approach presents several advantages including the “in vivo” measure of different cytochromes and transporter P-gp activities, their simultaneous determination in a single test, avoiding the influence of variability over time on phenotyping results, the administration of low dose substrates, a limited sampling strategy with an analytical method developed on DBS analysis. The goal of this project is to explore the relationship between the activity of drug-metabolizing enzymes (DME), assessed by a phenotypic approach, and the concentrations of Venlafaxine (VLX) + O-demethyl-venlafaxine (ODV), the efficacy and tolerance of VLX. Methods/design This study is a multicentre prospective non-randomized open trial. Eligible patients present a major depressive episode, MADRS over or equal to 20, treatment with VLX regardless of the dose during at least 4 weeks. The Phenotype Visit includes VLX and ODV concentration measurement. Following the oral absorption of low doses of omeprazole, midazolam, dextromethorphan, and fexofenadine, drug metabolizing enzymes activity is assessed by specific metabolite/probe concentration ratios from a sample taken 2 h after cocktail administration for CYP2C19, CYP3A4, CYP2D6; and by the determination of the limited area under the curve from the capillary blood samples taken 2–3 and 6 h after cocktail administration for CYP2C19 and P-gp. Two follow-up visits will take place between 25 and 40 days and 50–70 days after inclusion. They include assessment of efficacy, tolerance and observance. Eleven french centres are involved in recruitment, expected to be completed within approximately 2 years with 205 patients. Metabolic ratios are determined in Geneva, Switzerland. Discussion By showing an association between drug metabolism and VLX concentrations, efficacy and tolerance, there is a hope that testing drug metabolism pathways with a phenotypical approach would help physicians in selecting and dosing antidepressants. The MARVEL study will provide an important contribution to increasing the knowledge of VLX variability and in optimizing the use of methods of personalized therapy in psychiatric settings. Trial registration ClinicalTrials.gov NCT02590185 (10/27/2015). This study is currently recruiting participants.
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- 2017
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40. Outcomes of 4 years of molecular genetic diagnosis on a panel of genes involved in premature aging syndromes, including laminopathies and related disorders
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Grelet, Maude, Blanck, Véronique, Sigaudy, Sabine, Philip, Nicole, Giuliano, Fabienne, Khachnaoui, Khaoula, Morel, Godelieve, Grotto, Sarah, Sophie, Julia, Poirsier, Céline, Lespinasse, James, Alric, Laurent, Calvas, Patrick, Chalhoub, Gihane, Layet, Valérie, Molin, Arnaud, Colson, Cindy, Marsili, Luisa, Edery, Patrick, Lévy, Nicolas, and De Sandre-Giovannoli, Annachiara
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- 2019
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41. Compositional diversity of rehabilitated tropical lands supports multiple ecosystem services and buffers uncertainties
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Thomas Knoke, Carola Paul, Patrick Hildebrandt, Baltazar Calvas, Luz Maria Castro, Fabian Härtl, Martin Döllerer, Ute Hamer, David Windhorst, Yolanda F. Wiersma, Giulia F. Curatola Fernández, Wolfgang A. Obermeier, Julia Adams, Lutz Breuer, Reinhard Mosandl, Erwin Beck, Michael Weber, Bernd Stimm, Wolfgang Haber, Christine Fürst, and Jörg Bendix
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Science - Abstract
Land use becomes more diverse when it considers uncertain interactions of multiple ecosystem services. Here, Knoke and colleagues show that uncertainty plays a larger role if ecosystem services are optimized only for a single service, or if services correlate.
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- 2016
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42. The spectrum of renal involvement in male patients with infertility related to excretory-system abnormalities: phenotypes, genotypes, and genetic counseling
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Mieusset, Roger, Fauquet, Isabelle, Chauveau, Dominique, Monteil, Laetitia, Chassaing, Nicolas, Daudin, Myriam, Huart, Antoine, Isus, François, Prouheze, Cathy, Calvas, Patrick, Bieth, Eric, Bujan, Louis, and Faguer, Stanislas
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- 2017
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43. Validation of a clinical practice-based algorithm for the diagnosis of autosomal recessive cerebellar ataxias based on NGS identified cases
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Mallaret, Martial, Renaud, Mathilde, Redin, Claire, Drouot, Nathalie, Muller, Jean, Severac, Francois, Mandel, Jean Louis, Hamza, Wahiba, Benhassine, Traki, Ali-Pacha, Lamia, Tazir, Meriem, Durr, Alexandra, Monin, Marie-Lorraine, Mignot, Cyril, Charles, Perrine, Van Maldergem, Lionel, Chamard, Ludivine, Thauvin-Robinet, Christel, Laugel, Vincent, Burglen, Lydie, Calvas, Patrick, Fleury, Marie-Céline, Tranchant, Christine, Anheim, Mathieu, and Koenig, Michel
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- 2016
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44. Editorial to the special issue on “Molecular Genetics of Developmental Eye Disorders”
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Ragge, Nicola, Calvas, Patrick, and Chassaing, Nicolas
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- 2019
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45. The need for widely available genomic testing in rare eye diseases: an ERN-EYE position statement
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Black G. C., Sergouniotis P., Sodi A., Leroy B. P., Van Cauwenbergh C., Liskova P., Gronskov K., Klett A., Kohl S., Taurina G., Sukys M., Haer-Wigman L., Nowomiejska K., Marques J. P., Leroux D., Cremers F. P. M., De Baere E., Dollfus H., Ashworth J., Audo I., Bacci G., Balciuniene V. J., Bargiacchi S., Bertelsen M., Black G., Boon C., Bremond-Gignac D., Buzzonetti L., Calvas P., Thomsen A. C., Chirita-Emandi A., Chokoshvili D., Cremers F., Daly A., Downes S., Fasolo A., Fasser C., Fischer D., Fortunato P., Gelzinis A., Hall G., Hamann S., Heon E., Iarossi G., Iberg C., Jouanjan G., Kaariainen H., Kahn K., Keegan D., Laengsfeld M., Leon A., Leroux B., Lorenz B., Maggi R., Mauring L., Melico P., Meunier I., Mohand-Said S., Monterosso C., Morandi P., Parmeggiani F., Passerini I., Pelletier V., Peluso F., Perdomo Y., Rapizzi E., Roos L., Roosing S., Rozet J. -M., Simonelli F., Sowden J., Stingl K., Suppiej A., Testa F., Tracewska A., Traficante G., Valeina S., Wheeler-Schilling T., Yu-Wai-Man P., Zeitz C., Zemaitiene R., Leroux, Dorothée [0000-0002-1412-6611], Apollo - University of Cambridge Repository, Ophthalmology, ANS - Complex Trait Genetics, Black, G. C., Sergouniotis, P., Sodi, A., Leroy, B. P., Van Cauwenbergh, C., Liskova, P., Gronskov, K., Klett, A., Kohl, S., Taurina, G., Sukys, M., Haer-Wigman, L., Nowomiejska, K., Marques, J. P., Leroux, D., Cremers, F. P. M., De Baere, E., Dollfus, H., Ashworth, J., Audo, I., Bacci, G., Balciuniene, V. J., Bargiacchi, S., Bertelsen, M., Black, G., Boon, C., Bremond-Gignac, D., Buzzonetti, L., Calvas, P., Thomsen, A. C., Chirita-Emandi, A., Chokoshvili, D., Cremers, F., Daly, A., Downes, S., Fasolo, A., Fasser, C., Fischer, D., Fortunato, P., Gelzinis, A., Hall, G., Hamann, S., Heon, E., Iarossi, G., Iberg, C., Jouanjan, G., Kaariainen, H., Kahn, K., Keegan, D., Laengsfeld, M., Leon, A., Leroux, B., Lorenz, B., Maggi, R., Mauring, L., Melico, P., Meunier, I., Mohand-Said, S., Monterosso, C., Morandi, P., Parmeggiani, F., Passerini, I., Pelletier, V., Peluso, F., Perdomo, Y., Rapizzi, E., Roos, L., Roosing, S., Rozet, J. -M., Simonelli, F., Sowden, J., Stingl, K., Suppiej, A., Testa, F., Tracewska, A., Traficante, G., Valeina, S., Wheeler-Schilling, T., Yu-Wai-Man, P., Zeitz, C., and Zemaitiene, R.
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0301 basic medicine ,Eye Diseases ,lcsh:Medicine ,CHILDREN ,Position statement ,Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12] ,MOLECULAR-GENETICS ,0302 clinical medicine ,HISTORY ,Health care ,Medicine and Health Sciences ,Genetics(clinical) ,Pharmacology (medical) ,Child ,Genetics (clinical) ,medicine.diagnostic_test ,General Medicine ,Genomics ,Europe ,TRIALS ,ERN-EYE ,Rare eye diseases ,medicine.symptom ,Genetic and genomic testing ,Human ,medicine.medical_specialty ,Visual impairment ,LEBER CONGENITAL AMAUROSIS ,Socio-culturale ,DIAGNOSIS ,03 medical and health sciences ,Rare Diseases ,medicine ,Humans ,Genetic Testing ,Intensive care medicine ,Genetic testing ,business.industry ,CLINICAL-FEATURES ,lcsh:R ,Rare eye disease ,Eye Disease ,Human genetics ,Clinical trial ,030104 developmental biology ,Genomic ,030221 ophthalmology & optometry ,Personalized medicine ,business ,Rare disease - Abstract
Background Rare Eye Diseases (RED) are the leading cause of visual impairment and blindness for children and young adults in Europe. This heterogeneous group of conditions includes over 900 disorders ranging from relatively prevalent disorders such as retinitis pigmentosa to very rare entities such as developmental eye anomalies. A significant number of patients with RED have an underlying genetic etiology. One of the aims of the European Reference Network for Rare Eye Diseases (ERN–EYE) is to facilitate improvement in diagnosis of RED in European member states. Main body Technological advances have allowed genetic and genomic testing for RED. The outcome of genetic testing allows better understanding of the condition and allows reproductive and therapeutic options. The increase of the number of clinical trials for RED has provided urgency for genetic testing in RED. A survey of countries participating in ERN-EYE demonstrated that the majority are able to access some forms of genomic testing. However, there is significant variability, particularly regarding testing as part of clinical service. Some countries have a well-delineated rare disease pathway and have a national plan for rare diseases combined or not with a national plan for genomics in medicine. In other countries, there is a well-established organization of genetic centres that offer reimbursed genomic testing of RED and other rare diseases. Clinicians often rely upon research-funded laboratories or private companies. Notably, some member states rely on cross-border testing by way of an academic research project. Consequently, many clinicians are either unable to access testing or are confronted with long turnaround times. Overall, while the cost of sequencing has dropped, the cumulative cost of a genomic testing service for populations remains considerable. Importantly, the majority of countries reported healthcare budgets that limit testing. Short conclusion Despite technological advances, critical gaps in genomic testing remain in Europe, especially in smaller countries where no formal genomic testing pathways exist. Even within larger countries, the existing arrangements are insufficient to meet the demand and to ensure access. ERN-EYE promotes access to genetic testing in RED and emphasizes the clinical need and relevance of genetic testing in RED.
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- 2021
46. Ecuadorian banana farms should consider organic banana with low price risks in their land-use portfolios.
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Luz Maria Castro, Baltazar Calvas, and Thomas Knoke
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Medicine ,Science - Abstract
Organic farming is a more environmentally friendly form of land use than conventional agriculture. However, recent studies point out production tradeoffs that often prevent the adoption of such practices by farmers. Our study shows with the example of organic banana production in Ecuador that economic tradeoffs depend much on the approach of the analysis. We test, if organic banana should be included in economic land-use portfolios, which indicate how much of the land is provided for which type of land-use. We use time series data for productivity and prices over 30 years to compute the economic return (as annualized net present value) and its volatility (with standard deviation as risk measure) for eight crops to derive land-use portfolios for different levels of risk, which maximize economic return. We find that organic banana is included in land-use portfolios for almost every level of accepted risk with proportions from 1% to maximally 32%, even if the same high uncertainty as for conventional banana is simulated for organic banana. A more realistic, lower simulated price risk increased the proportion of organic banana substantially to up to 57% and increased annual economic returns by up to US$ 187 per ha. Under an assumed integration of both markets, for organic and conventional banana, simulated by an increased coefficient of correlation of economic return from organic and conventional banana (ρ up to +0.7), organic banana holds significant portions in the land-use portfolios tested only, if a low price risk of organic banana is considered. We conclude that uncertainty is a key issue for the adoption of organic banana. As historic data support a low price risk for organic banana compared to conventional banana, Ecuadorian farmers should consider organic banana as an advantageous land-use option in their land-use portfolios.
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- 2015
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47. Avoiding the loss of shade coffee plantations: how to derive conservation payments for risk-averse land-users
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Castro, Luz Maria, Calvas, Baltazar, Hildebrandt, Patrick, and Knoke, Thomas
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- 2013
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48. Rapid identification of mitochondrial DNA (mtDNA) mutations in neuromuscular disorders by using surveyor strategy
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Bannwarth, S., Procaccio, V., Rouzier, C., Fragaki, K., Poole, J., Chabrol, B., Desnuelle, C., Pouget, J., Azulay, J.P., Attarian, S., Pellissier, J.F., Gargus, J.J., Abdenur, J.E., Mozaffar, T., Calvas, P., Labauge, P., Pages, M., Wallace, D.C., Lambert, J.C., and Paquis-Flucklinger, V.
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- 2008
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49. Phenotype and genotype comparative study of typical, late onset and very late onset Friedreich ataxia: 1295
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Lecocq, C., Tranchant, C., Azulay, J.-P., NʼGuyen, K., Brice, A., Charles, P., Rai, M., Goizet, C., Tison, F., Guyant-Marechal, L., Pereon, Y., Calvas, P., Dürr, A., Koenig, M., Pandolfo, M., and Anheim, M.
- Published
- 2014
50. Bi-allelic variants in WNT7Bdisrupt the development of multiple organs in humans
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Bouasker, Samir, Patel, Nisha, Greenlees, Rebecca, Wellesley, Diana, Fares Taie, Lucas, Almontashiri, Naif A, Baptista, Julia, Alghamdi, Malak Ali, Boissel, Sarah, Martinovic, Jelena, Prokudin, Ivan, Holden, Samantha, Mudhar, Hardeep-Singh, Riley, Lisa G, Nassif, Christina, Attie-Bitach, Tania, Miguet, Marguerite, Delous, Marion, Ernest, Sylvain, Plaisancié, Julie, Calvas, Patrick, Rozet, Jean-Michel, Khan, Arif O, Hamdan, Fadi F, Jamieson, Robyn V, Alkuraya, Fowzan S, Michaud, Jacques L, and Chassaing, Nicolas
- Abstract
BackgroundPulmonary hypoplasia, Diaphragmatic anomalies, Anophthalmia/microphthalmia and Cardiac defects delineate the PDAC syndrome. We aim to identify the cause of PDAC syndrome in patients who do not carry pathogenic variants in RARBand STRA6, which have been previously associated with this disorder.MethodsWe sequenced the exome of patients with unexplained PDAC syndrome and performed functional validation of candidate variants.ResultsWe identified bi-allelic variants in WNT7Bin fetuses with PDAC syndrome from two unrelated families. In one family, the fetus was homozygous for the c.292C>T (p.(Arg98*)) variant whereas the fetuses from the other family were compound heterozygous for the variants c.225C>G (p.(Tyr75*)) and c.562G>A (p.(Gly188Ser)). Finally, a molecular autopsy by proxy in a consanguineous couple that lost two babies due to lung hypoplasia revealed that both parents carry the p.(Arg98*) variant. Using a WNT signalling canonical luciferase assay, we demonstrated that the identified variants are deleterious. In addition, we found that wnt7bbmutant zebrafish display a defect of the swimbladder, an air-filled organ that is a structural homolog of the mammalian lung, suggesting that the function of WNT7B has been conserved during evolution for the development of these structures.ConclusionOur findings indicate that defective WNT7B function underlies a form of lung hypoplasia that is associated with the PDAC syndrome, and provide evidence for involvement of the WNT–β-catenin pathway in human lung, tracheal, ocular, cardiac, and renal development.
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- 2023
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