A deep phenotyping approach to understand major depressive disorder and responses to antidepressant pharmacotherapy

Major depressive disorder (MDD) is a debilitating psychiatric disorder characterised by a complex underlying biology and poor response to pharmacological antidepressant strategies. Given the heterogeneity of MDD and the diverse range of available treatment options, there is an increasing desire to develop and implement precision medicine approaches to tailor existing treatment strategies to the biological system of the individual. In this thesis, high-resolution omics data (connectomics [fMRI], metabolomics [1H NMR] and immunomics [inflammatory cytokines]) collected from the Canadian Biomarker Integration Network in Depression (CAN-BIND) study has been integrated to facilitate the deep phenotyping of MDD. In addition, this approach has been used to predict the treatment response to two common antidepressant drugs, monotherapy with the selective serotonin reuptake inhibitor (SSRI) escitalopram (10-20 mg) or combination therapy with escitalopram and the dopaminergic antipsychotic aripiprazole (2-10 mg). This approach identified a multi-modal panel of sex-specific biomarkers of MDD and treatment response, highlighting a strong immunometabolic component in depressed males, but not females. Unsupervised clustering methods indicated the superiority of biological (neuroimaging) over symptom-based (clinical questionnaires) data for the stratification of patients into MDD subtypes with differential response to treatment. More importantly, a set of multi-modal, sex-specific biomarkers were identified that predicted treatment response with escitalopram monotherapy (84.7% accuracy) or aripiprazole augmentation (88.5% accuracy). In addition to highlighting potential new aspects of the biology of MDD (e.g. relevance of lipoprotein size and density for their relation to depression), this work is one of the first attempts to apply systems biology approaches to high-resolution biological data from a large clinical trial to predict later treatment outcome. With the validation of the findings presented in this thesis in independent cohorts, and with further development of omics technologies, leading to cheaper and high-throughput screening of the patient population, pre-dose biomarkers have the potential to achieve personalised treatment. Each year, escitalopram and aripiprazole are prescribed to an estimated 26 million and 7 million individuals respectively, and over one third of them do not respond. Thus, being able to predict response to antidepressant medication from baseline biomarkers has enormous clinical and socioeconomic benefits.Open Acces

Spatio-temporal entanglement of twin photons: an intuitive picture

We draw an intuitive picture of the spatio-temporal properties of the entangled state of twin photons, where they are described as classical wave-packets. This picture predicts a precise relation between their temporal and transverse spatial separations at the crystal output. The space-time coupling described by classical arguments turns out to determine in a precise way the spatio-temporal structure of the quantum entanglement, analysed by means of the biphotonic correlation and of the Schmidt dimensionality of the entanglement.Comment: 12 pages, 3 figure

Tailoring the spatiotemporal structure of biphoton entanglement in type-I parametric down-conversion

We investigate the spatiotemporal structure of the biphoton entangled state produced by parametric down-conversion (PDC) at the output face of the nonlinear crystal. We analyze the geometry of biphoton correlation for different gain regimes (from ultralow to high), different crystal lengths, and different tuning angles of the crystal. While for collinear or quasicollinear phase matching a X-shaped geometry, nonfactorizable in space and time, dominates, in the highly noncollinear conditions we observe a remarkable transition to a factorizable geometry. We show that the geometry of spatiotemporal correlation is a consequence of the angle-frequency relationship imposed by phase matching and that the fully spatiotemporal analysis provides a key to control the spatiotemporal properties of the PDC entangled state and in particular to access a biphoton localization in time and space in the femtosecond and micrometer range, respectively

La triade : une stratégie de supervision à redéfinir!

La présente étude descriptive à caractère exploratoire s’inscrit dans le contexte des réformes en éducation au Québec, plus particulièrement au baccalauréat en enseignement de l’éducation physique et à la santé (ÉPS). L’un des principaux défis qui touchent la formation initiale est sans doute celui d’assurer le développement des compétences professionnelles des futurs enseignants, notamment en cours de stage. À cet égard, il apparaît pertinent d’actualiser la stratégie de supervision pédagogique privilégiée lors des stages en ÉPS à l’Université du Québec à Trois-Rivières : la triade (stagiaire, enseignant associé et superviseur universitaire). Dans le cadre de la stratégie de supervision réalisée en triade, les objectifs de l’étude consistent à approfondir les représentations de chacun des acteurs en référence aux compétences professionnelles, à décrire les types de savoirs mobilisés et à définir les conditions favorables à la supervision. Les résultats issus d’un questionnaire auquel ont répondu les membres de la triade (N = 42) actifs à la session d’hiver 2007 révèlent certaines divergences entourant les représentations et les savoirs relatifs à la supervision en triade. La nécessité d’une vision commune en matière de développement professionnel conjuguée à la pertinence de points de vue jugés complémentaires entre les formateurs est discutée.This exploratory and descriptive study was conducted in the context of Québec’s education reforms, particularly in terms of teacher training for physical education and health. (PEH). Without a doubt, one of the major challenges of initial training is ensuring professional skill development among the future teachers during their practicums. To this effect, is seems important to update the pedagogical supervision strategy in place at University of Québec in Trois-Rivières: the triad: student teacher, supervising teacher, and university supervisor. In the framework of the triad supervision strategy, the objectives of the study consist of deepening the understanding each actor has of professional skills, describing the types of knowledge mobilized and identifying favourable supervision conditions. The results of a questionnaire given to the triad members (N = 42) who were active in the winter of 2007 session reveal certain discrepancies in their ideas and knowledge about triad supervision. The need for a common professional development vision and the relevance of complementary points of view among the trainers is discussed.El presente estudio descriptivo de tipo exploratorio se inscribe en el contexto de las reformas educativas en Quebec, más específicamente en formación docente en educación física y salud (EFS). Uno de los principales retos que tocan a la formación inicial es sin duda el de garantizar el desarrollo de las habilidades profesionales de los futuros maestros, sobre todo durante el período de práctica. Al respecto, es pertinente actualizar la estrategia de supervisión pedagógica privilegiada durante los períodos de práctica en EFS en la Universidad de Quebec en Trois-Rivières: la triada (practicante, maestro asociado y supervisor universitario). En el marco de la estrategia de supervisión en triada, los objetivos del estudio consisten en profundizar las representaciones de cada uno de los actores en lo que se refiere a las habilidades profesionales, describir los tipos de saber movilizados e identificar las condiciones que favorecen la supervisión. Los resultados provenientes de un cuestionario aplicado a los miembros de la triada (N=42) activos durantes la sesión del invierno de 2007 muestran ciertas divergencias en torno a las representaciones y los saberes relativos a la supervisión en triada. Se discute la necesidad de una visión común en materia de desarrollo profesional conjugada con la pertinencia de puntos de vista juzgados como complementarios entre los formadores

Museos virtuales y entorno construido: narrativas y experiencias inmersivas vía centros de geodatos multitemporales

[EN] Our built environment is nowadays considered as a dynamic complex, stretching and transforming across space and time, with the interaction of human, social and economic dimensions. It needs to be safeguarded as living places for the future taking into account such complexity. The general aim of this work is to contribute to the comprehension of landscape values, enhancing participation processes by tourists and local communities, considering the built environment as a system: the sum of natural transformation, ancient artefacts stratification and human activities, partially covering the tangible traces, and functioning as a vehicle for the comprehension of intangible values. Multi-temporal, multi-scale and geospatial datasets can play an important role in such knowledge transfer processes by means of narratives and immersive experiences in a multimedia museum approach. In particular, the cartographic heritage, in the form of metric and non-metric maps, can be progressively used as a source of information for innovative narratives. Virtual Museums (VMs)are additional "channels" to disseminate content and to provide knowledge about cultural heritage; they have emerged from the crossbreeding process between museums and digital technologies. Investigating how digital storytelling may support communication and understanding of complex systems, such as the built environment and landscape, it is relevant because cultural awareness may foster the sense of belonging and identity construction of which Europe is thirsty, contributing to the safeguarding of fragile sites. The paper provides useful information for museums that would like to follow this pathway. It retraces the main steps of storytelling production and presents interesting examples of immersive narrative models based on geospatial data and a virtual hub, helping people to retrieve and access information and to recognize places of memory mostly unknown. Moreover, it offers an evaluation of existing tools that can be adopted for this purpose. Eventually, by virtue of the research carried out for the case study of the Virtual Museum of Como Lake Landscape, the paper aims at ascertaining which kind of stories and experiences can be designed, the potential of these tools and possible weaknesses or constraints that deserve future researches.[ES] El entorno construido se considera hoy en día como un complejo dinámico, que se extiende y transforma a través del espacio y el tiempo, con interacción de dimensiones humanas, sociales y económicas. Debe salvaguardarse como lugares donde vivir el futuro teniendo en cuenta tal complejidad. El objetivo general de este trabajo es contribuir a la comprensión de los valores paisajísticos, potenciando los procesos de participación de los turistas y de los autóctonos, considerando el entorno construido como un sistema: suma de la transformación natural, de la estratificación de artefactos antiguos y de actividades humanas, cubriendo parcialmente los rastros tangibles, y vehículo de comprensión de valores intangibles. Los conjuntos de datos multitemporales, a multi-escala y geoespaciales pueden desempeñar un papel importante en dicho proceso de transferencia de conocimiento a través de narrativas y experiencias inmersivas en el enfoque de un museo multimedia. En particular, el patrimonio cartográfico, en forma de mapas métricos y mapas no métricos, puede utilizarse progresivamente como fuente de información para narrativas innovadoras. Los Museos Virtuales (VM) son “canales” adicionales que permiten difundir contenido y proporcionar conocimiento sobre el patrimonio cultural; surgen del proceso de mestizaje entre museos y tecnologías digitales. Investigar cómo la narración digital puede apoyar la comunicación y la comprensión de sistemas complejos, como el entorno construido y el paisaje, es relevante porque la conciencia cultural puede fomentar el sentido de pertenencia y la construcción de identidad de los que Europa tiene sed, contribuyendo a la protección de sitios frágiles. El artículo proporciona información útil para los museos que deseen seguir este camino. Describe los principales pasos que deberían considerarse a la hora de producir narrativas y pone ejemplos interesantes de modelos narrativos inmersivos basados en datos geoespaciales y centros virtuales, que ayudan a las personas a recuperar y acceder a información, y a reconocer lugares desconocidos o vagamente retenidos en la memoria. Además, ofrece una evaluación de las herramientas existentes que se pueden adoptar con este propósito. El objetivo es aclarar, finalmente, en virtud dela investigación desarrollada en el caso de estudio del Museo Virtual del Paisaje del Lago di Como, qué tipo de historias y experiencias se pueden diseñar, el potencial de estas herramientas y las posibles debilidades o limitaciones que merecen futuras investigaciones.We thank Stefano Della Torre (Head of Polimi dABC) as Sc. Responsible of the Advisory within the PORL FESR 2007/2013 ‘Multimedia system for the presentation and participated recognizing of the environmental values of the landscape of the Lake of Como’; and Leoni Marco (Director of the Museum of Como Lake Landscape) for the concession of museum’s data and his support in developing the PhD research of which this paper presents a summary of preliminary findings.The research leading to the results of this paper is partially funded under the ICT Policy Support Programme (ICT PSP) as part of the Competitiveness and Innovation Framework Programme by the European Community (CIP) GA no. 620400.Brumana, R.; Oreni, D.; Caspani, S.; Previtali, M. (2018). Virtual museums and built environment: narratives and immersive experience via multi-temporal geodata hub. Virtual Archaeology Review. 9(19):34-49. https://doi.org/10.4995/var.2018.9918SWORD3449919Bedford, L. (2001). Storytelling: The real work of museums. Curator: the museum journal, Vol. 44, Issue 1, 27-34. doi: 10.1111/j.2151-6952.2001.tb00027.xBarazzetti, L., Brumana, R., Oreni, D., & Roncoroni, F. (2013). Recognizing landscapes: can we change the point of view of geographic data? Journal of Mobile Multimedia, Vol. 9(1-2), 39-52. doi: 10.1111/j.2151-6952.2001.tb00027.xBarazzetti, L., Brumana, R., Oreni, D., & Previtali, M. (2014). Historical Map Registration via Independent Model Adjustment with Affine Transformations. In ICCSA 2014 (pp. 44-56). doi: 10.1007/978-3-319-09147-1_4Barazzetti L., Brumana, R., Cuca, B., & Previtali, M. (2015). Towards a Virtual Hub for a wider Open Data community. In Geomatics Workbooks n° 12, "FOSS4G Europe Como 2015" (pp.1-12).Brumana, R., Cuca, B., Oreni, D., Prandi, F., & Scaioni, M. (2010). Integration of old cadastral maps into up-to-date geodatabases for urban planning. In Core spatial databases - updating maintenance and services. From theory to practice (pp. 90-95). Haifa, Israel.Brumana, R., Oreni, D., Cuca, B., Rampini, A., & Pepe, M. (2012). Open Access to Historical Atlas: Sources of Information and Services for Landscape Analysis in an SDI Framework. In ICCSA 2012 (pp. 397-413). Springer Int. Publishing. doi: 10.1007/978-3-642-31075-1_30.Brumana, R., Oreni, D., Van Hecke, L., Barazzetti, L., Previtali, M., Roncoroni, F., & Valente, R. (2013). Combined Geometric and Thermal Analysis from Uav Platforms for Archaeological Heritage Documentation. In XXIV International Cipa Symposium (pp. 49-54). Strasbourg, France.Brumana, R., Santana Quintero, M., Barazzetti, L., Previtali, M., Della Torre, S., Roels, D., & Capitani, M. (2015). A geo-swot chart, using a values centered approach and multitemporal-maps for landscape assessment and multimedia ecomuseum. In ICOMOS International Symposium "Heritage and Landscape as Human Values, Theme 1 "Sharing and experiencing the identity of communities through tourism and interpretation" (pp. 186-191). Florence, Italy.Bedford, L. (2001). Storytelling: The real work of museums. Curator: the Museum Journal, 44(1), 27-34.https://doi.org/10.1111/j.2151-6952.2001.tb00027.xBarazzetti, L., Brumana, R., Oreni, D., & Roncoroni, F. (2013). Recognizing landscapes: can we change the point of view of geographic data? Journal of Mobile Multimedia, 9(1-2), 39-52.Barazzetti, L., Brumana, R., Oreni, D., & Previtali, M. (2014). Historical Map Registration via Independent Model Adjustment with Affine Transformations. In ICCSA 2014 (pp. 44-56). Guimaraes, Portugal. https://doi.org/10.1007/978-3-319-09147-1_4Barazzetti, L., Brumana, R., Cuca, B., & Previtali, M. (2015). Towards a Virtual Hub for a wider Open Data community. In FOSS4G Europe 2015(pp.1-12). Como, Italy.Brumana, R., Cuca, B., Oreni, D., Prandi, F., & Scaioni, M. (2010). Integration of old cadastral maps into up-to-date geodatabases for urban planning. The International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences, XXXVIII, 4-8-2/W9, 90-95.Brumana, R., Oreni, D., Cuca, B., Rampini, A., &Pepe, M. (2012). Open Access to Historical Atlas: Sources of Information and Services for Landscape Analysis in an SDI Framework .In ICCSA 2012(pp. 397-413).Salvador de Bahia, Brazil. https://doi.org/10.1007/978-3-642-31075-1_30Brumana, R., Oreni, D., Van Hecke, L., Barazzetti, L., Previtali, M., Roncoroni, F., & Valente, R. (2013). Combined geometric and thermal analysis from UAV platforms for archaeological heritage documentation. ISPRS Annals of the Photogrammetry, Remote Sensing and Spatial Information Science, II-5/W1, 49-54. https://doi.org/10.5194/isprsannals-II-5-W1-49-2013Brumana, R., Santana Quintero, M., Barazzetti, L., Previtali, M., Della Torre, S., Roels, D., & Capitani, M. (2015a). A geo-swot chart, using a values centered approach and multi temporal-maps for landscape assessment and multimedia ecomuseum. In ICOMOS International Symposium "Heritage and Landscape as Human Values", Theme 1"Sharing and experiencing the identity of communities through tourism and interpretation" (pp. 186-191). Florence, Italy.Brumana, R., Santana Quintero, M., Barazzetti, L., Previtali, M., Banfi, F., Oreni, D., Roels D., & Roncoroni, F. (2015b). Towards a virtual hub approach for landscape assessment and multimedia ecomuseum using multi temporal-maps. The International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences, XL-5/W7, 49-56. https://doi.org/10.5194/isprsarchives-XL-5-W7-49-2015Bruner, J. (1991). The Narrative Construction of Reality. Critical Inquiry, 18 (1), 1-21. https://doi.org/10.1086/448619Caquard, S. (2013). Mapping narrative cartography. Progress in Human Geography, 37(1), 135-144.https://doi.org/10.1177/0309132511423796Caspani, S., Brumana, R., Oreni, D., Previtali, M. (2017). Virtual museums as digital storytellers for dissemination of built environment: possible narratives and outlooks for appealing and rich encounters with the past. The International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences, XLII-2/W5, 113-119.https://doi.org/10.5194/isprs-archives-XLII-2-W5-113-2017Castells, M. (2000). The construction of European Identity. Retrieved October25, 2017, fromhttps://www.chet.org.za/files/CASTELLS%202004%20European%20Identity.pdfCouncil of Europe. (2000). European Landscape Convention. Retrieved October25, 2017, from https://rm.coe.int/1680080621Cuca, B., Brumana, R., Scaioni, M., & Oreni, D. (2011). Spatial Data Management of Temporal Map Series for Cultural and Environmental Heritage. International Journal of Spatial Data Infrastructures Research, 6, 97-125.https.//doi.org/10.2902/1725-0463.2011.06.art5Cuca, B., Previtali, M., Barazzetti, L., & Brumana, R. (2017). Benefits of using Open Geo-spatial Data for valorization of Cultural Heritage: GeoPan app. In 19th EGU General Assembly (p. 19101). Wien, Austria. Retrieved June 20, 2018, from https://meetingorganizer.copernicus.org/EGU2017/EGU2017-19101.pdfGiaccardi, E., & Fogli, D. (2008). Affective geographies: toward a richer cartographic semantics for the geospatial web. In AVI 8 Proceedings of the working conference on Advanced visual interfaces (pp. 173-180). Napoli, Italy. https://doi.org/10.1145/1385569.1385598Hooper-Greenhill, E. (2005). I musei e la formazione del sapere: le radici storiche, le pratiche del presente. Milan: Il Saggiatore.ICOMOS. (1996). The Declaration of San Antonio. Retrieved April 1, 2018, from https://www.icomos.org/en/charters-and-texts/179-articles-en-francais/ressources/charters-and-standards/188-the-declaration-of-san-antonioICOMOS. (2008a). Charter on cultural routes. Retrieved April 1, 2018, from https://www.icomos.org/images/DOCUMENTS/Charters/culturalroutes_e.pdfICOMOS. (2008b). Quebèc Declaration on the preservation of the spirit of place. Retrieved April 1, 2018, from https://www.icomos.org/quebec2008/quebec_declaration/pdf/GA16_Quebec_Declaration_Final_EN.pdfICOMOS. (2014). The Florence Declaration on Heritage and Landscapes as Human Values. Retrieved April 1, 2018, from https://www.icomos.org/images/DOCUMENTS/Secretariat/2015/GA_2014_results/GA2014_Symposium_FlorenceDeclaration_EN_final_20150318.pdfMacdonald, S. (2013) .Memorylands: Heritage and Identity in Europe Today. London: Routledge.Monti, C., Achille, C., Brumana, R., Musumeci, S., Oreni, D., & Signori, M. (2009). Perspectives on the 3-D analysis through the cadastral map series (XVIII -XX sec.) and the first geodetic large scale map of Milan realized by the 'Astronomidi Brera' (Astronomers of Brera): toward an advanced portal. E-PERIMETRON, 4(2), 86-100.Nativi, S., Craglia, M., & Pearlman, J. (2013). Earth science infrastructures interoperability: the brokering approach. IEEE Journal of Selected Topics. Applied Earth Observations and Remote Sensing, 6(3), 1118-1129. https://doi.org/10.1109/JSTARS.2013.2243113Pierdicca, R., Malinverni, E., Frontoni, E., Colosi, F., & Orazi, R. (2016). 3D visualization tools to explore ancient architectures in South America. Virtual Archaeology Review, 7(15), 44-53.https://doi.org/10.4995/var.2016.5904Pini, L. (2003). Tremezzo il paese dove fioriscono I limoni. Tremezzo: Silvana Editoriale.Previtali, M. (2017). Geopan atl@s: A brokering based gateway to georeferenced historical maps for risk analysis. The International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences, XLII-2/W5, 583-589.https://doi.org/10.5194/isprs-archives-XLII-2-W5-583-2017Redweik, P., Cláudio, A., Carmo, M., Naranjo, J., & Sanjosé, J. (2017). Digital preservation of cultural and scientific heritage: involving university students to raise awareness of its importance. Virtual Archaeology Review, 8(16), 22-34. https://doi.org/10.4995/var.2017.4629Scazzosi, L. (2003). Landscape and Cultural Landscape: European Landscape Convention and UNESCO Policy .World Heritage papers, 7, 55-59.Scazzosi, L., (2004).Reading and assessing the landscape as cultural and historical heritage. Landscape Research, 29(4), 335-355.https://doi.org/10.1080/0142639042000288993ViMM. (2018).Virtual Multimodal Museum. Retrieved April 1, 2018, from https://www.vi-mm.euV-MUST. (2015). D. 2.3c State of the art on Virtual Museums in Europe and outside Europe: Report. Commissioned by the V-MUST project. Retrieved October25, 2017, from http://www.v-must.net/sites/default/files/D2.3d_StateArt_VirtualMuseums_2015.pdfWong, A. (2015). The whole story, and then some: 'digital storytelling' in evolving museum practice. In MW2015: Museums and the Web 2015, Chicago, United States. Retrieved October25, 2017, from http://mw2015.museumsandtheweb.com/paper/the-whole-story-and-then-some-digital-storytelling-in-evolving-museum-practice

Spatiotemporal structure of biphoton entanglement in type-II parametric down-conversion

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High-sensitivity imaging with multi-mode twin beams

Twin entangled beams produced by single-pass parametric down-conversion (PDC) offer the opportunity to detect weak amount of absorption with an improved sensitivity with respect to standard techniques which make use of classical light sources. We propose a differential measurement scheme which exploits the spatial quantum correlation of type II PDC to image a weak amplitude object with a sensitivity beyond the standard quantum limit imposed by shot-noise.Comment: 13 pages, 8 figure

Information Extraction from Documents: Question Answering vs Token Classification in real-world setups

Research in Document Intelligence and especially in Document Key Information Extraction (DocKIE) has been mainly solved as Token Classification problem. Recent breakthroughs in both natural language processing (NLP) and computer vision helped building document-focused pre-training methods, leveraging a multimodal understanding of the document text, layout and image modalities. However, these breakthroughs also led to the emergence of a new DocKIE subtask of extractive document Question Answering (DocQA), as part of the Machine Reading Comprehension (MRC) research field. In this work, we compare the Question Answering approach with the classical token classification approach for document key information extraction. We designed experiments to benchmark five different experimental setups : raw performances, robustness to noisy environment, capacity to extract long entities, fine-tuning speed on Few-Shot Learning and finally Zero-Shot Learning. Our research showed that when dealing with clean and relatively short entities, it is still best to use token classification-based approach, while the QA approach could be a good alternative for noisy environment or long entities use-cases

On-chip Quantum State Generation by Means of Integrated Frequency Combs

Summary form only given. This paper investigates different approaches to generate optical quantum states by means of integrated optical frequency combs. These include the generation of multiplexed heralded single-photons, the first realization of cross-polarized photon-pairs on a photonic chip, the first generation of multiple two-photon entangled states, and the first realizations of multi-photon entangled quantum states on a photonic chip