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Nephronophthisis (NPH) is an autosomal-recessive ciliopathy representing one of the most frequent causes of kidney failure in childhood characterized by a broad clinical and genetic heterogeneity. Applied to one of the worldwide largest cohorts of patients with NPH, genetic analysis encompassing targeted and whole exome sequencing identified disease-causing variants in 600 patients from 496 families with a detection rate of 71%. Of 788 pathogenic variants, 40 known ciliopathy genes were identified. However, the majority of patients (53%) bore biallelic pathogenic variants in NPHP1. NPH-causing gene alterations affected all ciliary modules defined by structural and/or functional subdomains. Seventy six percent of these patients had progressed to kidney failure, of which 18% had an infantile form (under five years) and harbored variants affecting the Inversin compartment or intraflagellar transport complex A. Forty eight percent of patients showed a juvenile (5-15 years) and 34% a late-onset disease (over 15 years), the latter mostly carrying variants belonging to the Transition Zone module. Furthermore, while more than 85% of patients with an infantile form presented with extra-kidney manifestations, it only concerned half of juvenile and late onset cases. Eye involvement represented a predominant feature, followed by cerebellar hypoplasia and other brain abnormalities, liver and skeletal defects. The phenotypic variability was in a large part associated with mutation types, genes and corresponding ciliary modules with hypomorphic variants in ciliary genes playing a role in early steps of ciliogenesis associated with juvenile-to-late onset NPH forms. Thus, our data confirm a considerable proportion of late-onset NPH suggesting an underdiagnosis in adult chronic kidney disease.

In medical research, the traditional way to collect data, i.e. browsing patient files, has been proven to induce bias, errors, human labor and costs. We propose a semi-automated system able to extract every type of data, including notes. The Smart Data Extractor pre-populates clinic research forms by following rules. We performed a cross-testing experiment to compare semi-automated to manual data collection. 20 target items had to be collected for 79 patients. The average time to complete one form was 6'81'' for manual data collection and 3'22'' with the Smart Data Extractor. There were also more mistakes during manual data collection (163 for the whole cohort) than with the Smart Data Extractor (46 for the whole cohort). We present an easy to use, understandable and agile solution to fill out clinical research forms. It reduces human effort and provides higher quality data, avoiding data re-entry and fatigue induced errors., Comment: IOS Press, 2023, Studies in Health Technology and Informatics

Background: Artificial intelligence (AI) has the potential to transform our healthcare systems significantly. New AI technologies based on machine learning approaches should play a key role in clinical decision-making in the future. However, their implementation in health care settings remains limited, mostly due to a lack of robust validation procedures. There is a need to develop reliable assessment frameworks for the clinical validation of AI. We present here an approach for assessing AI for predicting treatment response in triple-negative breast cancer (TNBC), using real-world data and molecular -omics data from clinical data warehouses and biobanks. Methods: The European “ITFoC (Information Technology for the Future Of Cancer)” consortium designed a framework for the clinical validation of AI technologies for predicting treatment response in oncology. Results: This framework is based on seven key steps specifying: (1) the intended use of AI, (2) the target population, (3) the timing of AI evaluation, (4) the datasets used for evaluation, (5) the procedures used for ensuring data safety (including data quality, privacy and security), (6) the metrics used for measuring performance, and (7) the procedures used to ensure that the AI is explainable. This framework forms the basis of a validation platform that we are building for the “ITFoC Challenge”. This community-wide competition will make it possible to assess and compare AI algorithms for predicting the response to TNBC treatments with external real-world datasets. Conclusions: The predictive performance and safety of AI technologies must be assessed in a robust, unbiased and transparent manner before their implementation in healthcare settings. We believe that the consideration of the ITFoC consortium will contribute to the safe transfer and implementation of AI in clinical settings, in the context of precision oncology and personalized care.

Background: Artificial intelligence (AI) has the potential to transform our healthcare systems significantly. New AI technologies based on machine learning approaches should play a key role in clinical decision-making in the future. However, their implementation in health care settings remains limited, mostly due to a lack of robust validation procedures. There is a need to develop reliable assessment frameworks for the clinical validation of AI. We present here an approach for assessing AI for predicting treatment response in triple-negative breast cancer (TNBC), using real-world data and molecular -omics data from clinical data warehouses and biobanks. Methods: The European “ITFoC (Information Technology for the Future Of Cancer)” consortium designed a framework for the clinical validation of AI technologies for predicting treatment response in oncology. Results: This framework is based on seven key steps specifying: (1) the intended use of AI, (2) the target population, (3) the timing of AI evaluation, (4) the datasets used for evaluation, (5) the procedures used for ensuring data safety (including data quality, privacy and security), (6) the metrics used for measuring performance, and (7) the procedures used to ensure that the AI is explainable. This framework forms the basis of a validation platform that we are building for the “ITFoC Challenge”. This community-wide competition will make it possible to assess and compare AI algorithms for predicting the response to TNBC treatments with external real-world datasets. Conclusions: The predictive performance and safety of AI technologies must be assessed in a robust, unbiased and transparent manner before their implementation in healthcare settings. We believe that the consideration of the ITFoC consortium will contribute to the safe transfer and implementation of AI in clinical settings, in the context of precision oncology and personalized care.

Background General practitioners (GPs) play a key role in managing the COVID-19 outbreak. However, they may encounter difficulties adapting their practices to the pandemic. We provide here an analysis of guidelines for the reorganisation of GP surgeries during the beginning of the pandemic from 15 countries. Methods A network of GPs collaborated together in a three-step process: (i) identification of key recommendations of GP surgery reorganisation, according to WHO, CDC and health professional resources from health care facilities; (ii) collection of key recommendations included in the guidelines published in 15 countries; (iii) analysis, comparison and synthesis of the results. Results Recommendations for the reorganisation of GP surgeries of four types were identified: (i) reorganisation of GP consultations (cancelation of non-urgent consultations, follow-up via e-consultations), (ii) reorganisation of GP surgeries (area partitioning, visual alerts and signs, strict hygiene measures), (iii) reorganisation of medical examinations by GPs (equipment, hygiene, partial clinical examinations, patient education), (iv) reorganisation of GP staff (equipment, management, meetings, collaboration with the local community). Conclusions We provide here an analysis of guidelines for the reorganisation of GP surgeries during the beginning of the COVID-19 outbreak from 15 countries. These guidelines focus principally on clinical care, with less attention paid to staff management, and the area of epidemiological surveillance and research is largely neglected. The differences of guidelines between countries and the difficulty to apply them in routine care, highlight the need of advanced research in primary care. Thereby, primary care would be able to provide recommendations adapted to the real-world settings and with stronger evidence, which is especially necessary during pandemics.

We leveraged the largely untapped resource of electronic health record data to address critical clinical and epidemiological questions about Coronavirus Disease 2019 (COVID-19). To do this, we formed an international consortium (4CE) of 96 hospitals across five countries (www.covidclinical.net). Contributors utilized the Informatics for Integrating Biology and the Bedside (i2b2) or Observational Medical Outcomes Partnership (OMOP) platforms to map to a common data model. The group focused on temporal changes in key laboratory test values. Harmonized data were analyzed locally and converted to a shared aggregate form for rapid analysis and visualization of regional differences and global commonalities. Data covered 27,584 COVID-19 cases with 187,802 laboratory tests. Case counts and laboratory trajectories were concordant with existing literature. Laboratory tests at the time of diagnosis showed hospital-level differences equivalent to country-level variation across the consortium partners. Despite the limitations of decentralized data generation, we established a framework to capture the trajectory of COVID-19 disease in patients and their response to interventions.

We leveraged the largely untapped resource of electronic health record data to address critical clinical and epidemiological questions about Coronavirus Disease 2019 (COVID-19). To do this, we formed an international consortium (4CE) of 96 hospitals across five countries (www.covidclinical.net). Contributors utilized the Informatics for Integrating Biology and the Bedside (i2b2) or Observational Medical Outcomes Partnership (OMOP) platforms to map to a common data model. The group focused on temporal changes in key laboratory test values. Harmonized data were analyzed locally and converted to a shared aggregate form for rapid analysis and visualization of regional differences and global commonalities. Data covered 27,584 COVID-19 cases with 187,802 laboratory tests. Case counts and laboratory trajectories were concordant with existing literature. Laboratory tests at the time of diagnosis showed hospital-level differences equivalent to country-level variation across the consortium partners. Despite the limitations of decentralized data generation, we established a framework to capture the trajectory of COVID-19 disease in patients and their response to interventions.

Due to the rapid growth of information available about individual patients, most physicians suffer from information overload when they review patient information in health information technology systems. In this manuscript, we present a novel hybrid dynamic and multi-collaborative filtering method to improve information retrieval from electronic health records. This method recommends relevant information from electronic health records for physicians during patient visits. It models information search dynamics using a Markov model. It also leverages the key idea of collaborative filtering, originating from Recommender Systems, to prioritize information based on various similarities among physicians, patients and information items. We tested this new method using real electronic health record data from the Indiana Network for Patient Care. Our experimental results demonstrated that for 46.7% of testing cases, this new method is able to correctly prioritize relevant information among top-5 recommendations that physicians are truly interested in., Comment: 18 pages, 11 figures, 8 tables

In this study, we evaluated the RNNG, a neural top-down transition based parser, for medication information extraction in clinical texts. We evaluated this model on a French clinical corpus. The task was to extract the name of a drug (or a drug class), as well as attributes informing its administration: frequency, dosage, duration, condition and route of administration. We compared the RNNG model that jointly identifies entities, events and their relations with separate BiLSTMs models for entities, events and relations as baselines. We call seq-BiLSTMs the baseline models for relations extraction that takes as extra-input the output of the BiLSTMs for entities and events. Similarly, we evaluated seq-RNNG, a hybrid RNNG model that takes as extra-input the output of the BiLSTMs for entities and events. RNNG outperforms seq-BiLSTM for identifying complex relations, with on average 88.1 [84.4-91.6] % versus 69.9 [64.0-75.4] F-measure. However, RNNG tends to be weaker than the baseline BiLSTM on detecting entities, with on average 82.4 [80.8-83.8] versus 84.1 [82.7-85.6] % F- measure. RNNG trained only for detecting relations tends to be weaker than RNNG with the joint modelling objective, 87.4% [85.8-88.8] versus 88.5% [87.2-89.8]. Seq-RNNG is on par with BiLSTM for entities (84.0 [82.6-85.4] % F-measure) and with RNNG for relations (88.7 [87.4-90.0] % F-measure). The performance of RNNG on relations can be explained both by the model architecture, which provides inductive bias to capture the hierarchy in the targets, and the joint modeling objective which allows the RNNG to learn richer representations. RNNG is efficient for modeling relations between entities or/and events in medical texts and its performances are close to those of a BiLSTM for entity and event detection.

Over recent years, continuous price decreases of PV system components and technological improvements, leading to better efficiency and reliability, contributed to reinforce the attractiveness of this technology. This is a trend that also benefitted building-integrated photovoltaic (BIPV) systems, which have become more affordable. In addition, it appears that the sector is dynamic and able to gain traction, as the significant number of competitors on the market tends to demonstrate. Nevertheless, in spite of this multiplicity of existing integrated PV products and the apparent market opportunities, deployment of BIPV solutions remains limited. Among the explanatory factors for this observation, one can cite the lack of appropriate business models or, at least, the lack of business models with a clear value proposition for BIPV systems. Possible drivers for BIPV system installation are crucial in order to define a value proposition that is as efficient as possible, as well as a business model. To refine the understanding of these drivers, the first chapter of this report explores these aspects in depth in section 2. The value of BIPV is not purely the economic value from electricity generation; it can also be connected to contributing to the local transition of the energy system, locally produced electricity, sustainability and marketing. The value of BIPV can be leveraged by companies willing to highlight a vision or mission that reaches beyond profit-oriented goals. Also, as a building component, BIPV can provide the same or better building functionalities as other building materials and help at the same time to meet legal requirements in terms of energy performance of buildings. Finally, the ability of BIPV solutions to improve real estate value is evoked as well, increasing the attractiveness of such investments, provided that the involved stakeholders can take advantage of this value. Different stakeholders involved in the business models are highlighted. They c, IEA PVPS Task 15 Enabling Framework for the Development of BIPV

Aujourd'hui, dans l'Église Catholique Romaine, des nouvelles formes de communautés « associatives » émergent et posent un certain nombre de questions au regard du droit canonique. L'une d'entre elles concerne les personnes qui font le choix du célibat, comme signe d'une « consécration » dans ces nouvelles formes communautaire. En droit public français, des interrogations naissent aussi au sujet de ces nouvelles formes de vie consacrée : certaines d'entre elles acquièrent un statut d'association publique internationale en droit canonique, et demandent, par exemple, leur reconnaissance légale comme « congrégation religieuse » (notamment, quant à la sécurité sociale, au droit du travail, et d'autres encore) avec le statut congréganiste.Ce sont ces critères essentiels de « reconnaissance » que cette étude se propose de préciser, comme la profession des conseils évangéliques, les liens sacrés, la stabilité, une vie fraternelle, une soumission à une règle de vie approuvée. Il s'agit de manifester plus clairement l'état de vie consacrée dans ces mouvements qui attendent, pour une part, une certaine reconnaissance de la part de l'Église, sans compter les contentieux, relativement nombreux, relatifs notamment aux régimes de sécurité sociale et de retraites, devant les juridictions étatiques.Cédric Burgun est prêtre incardiné au diocèse de Metz, membre de la Communauté de l'Emmanuel. Il est enseignant-chercheur à temps plein à la Faculté de Droit Canonique à l'Institut Catholique de Paris.

Aujourd'hui, dans l'Église Catholique Romaine, des nouvelles formes de communautés « associatives » émergent et posent un certain nombre de questions au regard du droit canonique. L'une d'entre elles concerne les personnes qui font le choix du célibat, comme signe d'une « consécration » dans ces nouvelles formes communautaire. En droit public français, des interrogations naissent aussi au sujet de ces nouvelles formes de vie consacrée : certaines d'entre elles acquièrent un statut d'association publique internationale en droit canonique, et demandent, par exemple, leur reconnaissance légale comme « congrégation religieuse » (notamment, quant à la sécurité sociale, au droit du travail, et d'autres encore) avec le statut congréganiste.Ce sont ces critères essentiels de « reconnaissance » que cette étude se propose de préciser, comme la profession des conseils évangéliques, les liens sacrés, la stabilité, une vie fraternelle, une soumission à une règle de vie approuvée. Il s'agit de manifester plus clairement l'état de vie consacrée dans ces mouvements qui attendent, pour une part, une certaine reconnaissance de la part de l'Église, sans compter les contentieux, relativement nombreux, relatifs notamment aux régimes de sécurité sociale et de retraites, devant les juridictions étatiques.Cédric Burgun est prêtre incardiné au diocèse de Metz, membre de la Communauté de l'Emmanuel. Il est enseignant-chercheur à temps plein à la Faculté de Droit Canonique à l'Institut Catholique de Paris.

Aujourd'hui, dans l'Église Catholique Romaine, des nouvelles formes de communautés « associatives » émergent et posent un certain nombre de questions au regard du droit canonique. L'une d'entre elles concerne les personnes qui font le choix du célibat, comme signe d'une « consécration » dans ces nouvelles formes communautaire. En droit public français, des interrogations naissent aussi au sujet de ces nouvelles formes de vie consacrée : certaines d'entre elles acquièrent un statut d'association publique internationale en droit canonique, et demandent, par exemple, leur reconnaissance légale comme « congrégation religieuse » (notamment, quant à la sécurité sociale, au droit du travail, et d'autres encore) avec le statut congréganiste.Ce sont ces critères essentiels de « reconnaissance » que cette étude se propose de préciser, comme la profession des conseils évangéliques, les liens sacrés, la stabilité, une vie fraternelle, une soumission à une règle de vie approuvée. Il s'agit de manifester plus clairement l'état de vie consacrée dans ces mouvements qui attendent, pour une part, une certaine reconnaissance de la part de l'Église, sans compter les contentieux, relativement nombreux, relatifs notamment aux régimes de sécurité sociale et de retraites, devant les juridictions étatiques.Cédric Burgun est prêtre incardiné au diocèse de Metz, membre de la Communauté de l'Emmanuel. Il est enseignant-chercheur à temps plein à la Faculté de Droit Canonique à l'Institut Catholique de Paris.

Aujourd'hui, dans l'Église Catholique Romaine, des nouvelles formes de communautés « associatives » émergent et posent un certain nombre de questions au regard du droit canonique. L'une d'entre elles concerne les personnes qui font le choix du célibat, comme signe d'une « consécration » dans ces nouvelles formes communautaire. En droit public français, des interrogations naissent aussi au sujet de ces nouvelles formes de vie consacrée : certaines d'entre elles acquièrent un statut d'association publique internationale en droit canonique, et demandent, par exemple, leur reconnaissance légale comme « congrégation religieuse » (notamment, quant à la sécurité sociale, au droit du travail, et d'autres encore) avec le statut congréganiste.Ce sont ces critères essentiels de « reconnaissance » que cette étude se propose de préciser, comme la profession des conseils évangéliques, les liens sacrés, la stabilité, une vie fraternelle, une soumission à une règle de vie approuvée. Il s'agit de manifester plus clairement l'état de vie consacrée dans ces mouvements qui attendent, pour une part, une certaine reconnaissance de la part de l'Église, sans compter les contentieux, relativement nombreux, relatifs notamment aux régimes de sécurité sociale et de retraites, devant les juridictions étatiques.Cédric Burgun est prêtre incardiné au diocèse de Metz, membre de la Communauté de l'Emmanuel. Il est enseignant-chercheur à temps plein à la Faculté de Droit Canonique à l'Institut Catholique de Paris.

Aujourd'hui, dans l'Église Catholique Romaine, des nouvelles formes de communautés « associatives » émergent et posent un certain nombre de questions au regard du droit canonique. L'une d'entre elles concerne les personnes qui font le choix du célibat, comme signe d'une « consécration » dans ces nouvelles formes communautaire. En droit public français, des interrogations naissent aussi au sujet de ces nouvelles formes de vie consacrée : certaines d'entre elles acquièrent un statut d'association publique internationale en droit canonique, et demandent, par exemple, leur reconnaissance légale comme « congrégation religieuse » (notamment, quant à la sécurité sociale, au droit du travail, et d'autres encore) avec le statut congréganiste.Ce sont ces critères essentiels de « reconnaissance » que cette étude se propose de préciser, comme la profession des conseils évangéliques, les liens sacrés, la stabilité, une vie fraternelle, une soumission à une règle de vie approuvée. Il s'agit de manifester plus clairement l'état de vie consacrée dans ces mouvements qui attendent, pour une part, une certaine reconnaissance de la part de l'Église, sans compter les contentieux, relativement nombreux, relatifs notamment aux régimes de sécurité sociale et de retraites, devant les juridictions étatiques.Cédric Burgun est prêtre incardiné au diocèse de Metz, membre de la Communauté de l'Emmanuel. Il est enseignant-chercheur à temps plein à la Faculté de Droit Canonique à l'Institut Catholique de Paris.

Au sein d’une organisation, de même qu’entre des organisations, il y a plusieurs intervenants qui doivent prendre des décisions en fonction de la vision qu’ils se font de l’organisation concernée, de son environnement et des interactions entre les deux. Dans la plupart des cas, les données sont fragmentées en plusieurs sources non coordonnées ce qui complique, notamment, le fait de retracer leur évolution chronologique. Ces différentes sources sont hétérogènes par leur structure, par la sémantique des données qu’elles contiennent, par les technologies informatiques qui les manipulent et par les règles de gouvernance qui les contrôlent. Dans ce contexte, un système de santé apprenant (Learning Health System) a pour objectif d’unifier les soins de santé, la recherche biomédicale et le transfert des connaissances, en offrant des outils et des services pour améliorer la collaboration entre les intervenants ; l’optique sous-jacente à cette collaboration étant de fournir à un individu de meilleurs services qui soient personnalisés. Les méthodes classiques de construction de modèle de données sont fondées sur des règles de pratique souvent peu précises, ad hoc, non automatisables. L’extraction des données d’intérêt implique donc d’importantes mobilisations de ressources humaines. De ce fait, la conciliation et l’agrégation des sources sont sans cesse à recommencer parce que les besoins ne sont pas tous connus à l’avance, qu’ils varient au gré de l’évolution des processus et que les données sont souvent incomplètes. Pour obtenir l’interopérabilité, il est nécessaire d’élaborer une méthode automatisée de construction de modèle de données qui maintient conjointement les données brutes des sources et leur sémantique. Cette thèse présente une méthode qui permet, une fois qu’un modèle de connaissance est choisi, la construction d’un modèle de données selon des critères fondamentaux issus d’un modèle ontologique et d’un modèle relationnel temporel basé sur la logique des interval, Within an organization, many stakeholders must make decisions based on their vision of the organization, its environment, and the interactions between these two. In most cases, the data are fragmented in several uncoordinated sources, making it difficult, in particular, to trace their chronological evolution. These different sources are heterogeneous in their structure, in the semantics of the data they contain, in the computer technologies that manipulate them, and in the governance rules that control them. In this context, a Learning Health System aims to unify health care, biomedical research and knowledge transfer by providing tools and services to enhance collaboration among stakeholders in the health system to provide better and personalized services to the patient. The implementation of such a system requires a common data model with semantics, structure, and consistent temporal traceability that ensures data integrity. Traditional data model design methods are based on vague, non-automatable best practice rules where the extraction of data of interest requires the involvement of very important human resources. The reconciliation and the aggregation of sources are constantly starting over again because not all needs are known in advance and vary with the evolution of processes and data are often incomplete. To obtain an interoperable data model, an automated construction method that jointly maintains the source raw data and their semantics is required. This thesis presents a method that build a data model according to fundamental criteria derived from an ontological model, a relational model and a temporal model based on the logic of intervals. In addition, the method is semi-automated by an OntoRelα prototype. On the one hand, the use of ontologies to define the semantics of data is an interesting way to ensure a better semantic interoperability since it automatically expresses different logical axioms allowing the description of data and their links. On the

A series of mononuclear ruthenium(II) complexes containing the tetradentate ligand bis[4(4′-methyl-2,2′-bipyridyl)]-1,7-heptane have been synthesised and their biological properties examined. In the synthesis of the [Ru(phen′)(bb7)]2+ complexes (where phen′ = 1,10-phenanthroline and its 5-nitro-, 4,7-dimethyl- and 3,4,7,8-tetramethyl- derivatives), both the symmetric cis-α and non-symmetric cis-β isomers were formed. However, upon standing for a number of days (or more quickly under harsh conditions) the cis-β isomer converted to the more thermodynamically stable cis-α isomer. The minimum inhibitory concentrations (MIC) and the minimum bactericidal concentrations (MBC) of the ruthenium(II) complexes were determined against six strains of bacteria: Gram-positive Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA); and the Gram-negative Escherichia coli (E. coli) strains MG1655, APEC, UPEC and Pseudomonas aeruginosa (P. aeruginosa). The results showed that the [Ru(5-NO2phen)(bb7)]2+ complex had little or no activity against any of the bacterial strains. By contrast, for the other cis-α-[Ru(phen′)(bb7)]2+ complexes, the antimicrobial activity increased with the degree of methylation. In particular, the cis-α-[Ru(Me4phen)(bb7)]2+ complex showed excellent and uniform MIC activity against all bacteria. By contrast, the MBC values for the cis-α-[Ru(Me4phen)(bb7)]2+ complex varied considerably across the bacteria and even within S. aureus and E. coli strains. In order to gain an understanding of the relative antimicrobial activities, the DNA-binding affinity, cellular accumulation and water–octanol partition coefficients (log P) of the ruthenium complexes were determined. Interestingly, all the [Ru(phen′)(bb7)]2+ complexes exhibited stronger DNA binding affinity (Ka ≈ 1 × 107 M−1) than the well-known DNA-intercalating complex [Ru(phen)2(dppz)]2+ (where dppz = dipyrido[3,2-a:2′,3′-c]phenazine).

In the biomedical domain, the lack of sharable datasets often limit the possibility of developing natural language processing systems, especially dialogue applications and natural language understanding models. To overcome this issue, we explore data generation using templates and terminologies and data augmentation approaches. Namely, we report our experiments using paraphrasing and word representations learned on a large EHR corpus with Fasttext and ELMo, to learn a NLU model without any available dataset. We evaluate on a NLU task of natural language queries in EHRs divided in slot-filling and intent classification sub-tasks. On the slot-filling task, we obtain a F-score of 0.76 with the ELMo representation; and on the classification task, a mean F-score of 0.71. Our results show that this method could be used to develop a baseline system., Comment: Machine Learning for Health (ML4H) Workshop at NeurIPS 2018 arXiv:1811.07216

Background: Choosing the most performing method in terms of outcome prediction or variables selection is a recurring problem in prognosis studies, leading to many publications on methods comparison. But some aspects have received little attention. First, most comparison studies treat prediction performance and variable selection aspects separately. Second, methods are either compared within a binary outcome setting (based on an arbitrarily chosen delay) or within a survival setting, but not both. In this paper, we propose a comparison methodology to weight up those different settings both in terms of prediction and variables selection, while incorporating advanced machine learning strategies. Methods: Using a high-dimensional case study on a sickle-cell disease (SCD) cohort, we compare 8 statistical methods. In the binary outcome setting, we consider logistic regression (LR), support vector machine (SVM), random forest (RF), gradient boosting (GB) and neural network (NN); while on the survival analysis setting, we consider the Cox Proportional Hazards (PH), the CURE and the C-mix models. We then compare performances of all methods both in terms of risk prediction and variable selection, with a focus on the use of Elastic-Net regularization technique. Results: Among all assessed statistical methods assessed, the C-mix model yields the better performances in both the two considered settings, as well as interesting interpretation aspects. There is some consistency in selected covariates across methods within a setting, but not much across the two settings. Conclusions: It appears that learning withing the survival setting first, and then going back to a binary prediction using the survival estimates significantly enhance binary predictions.

« La famille est importante, elle est nécessaire pour la survie de l'humanité. S'il n'y a pas de famille, la survie culturelle de l'humanité est en danger. Que cela nous plaise ou non, la famille est la base. » C'est ce que disait le pape François à la radio de l'archidiocèse de Rio de Janeiro, le 27 juillet 2013.En regardant la famille dans la réalité de sa beauté et l'appel de Dieu concernant notamment la vie conjugale, l'auteur, à la suite du synode sur la famille en octobre 2014 à Rome, insiste sur l'importance de la conversion de l'Église pour la famille qui ne doit pas être une pastorale comme une autre.La pastorale de la famille doit devenir une urgence de la « nouvelle évangélisation ». Le synode le dit exactement : « L'annonce de l'Évangile de la famille constitue une urgence pour la nouvelle évangélisation. L'Église est appelée à le mettre en pratique, avec une tendresse de mère et une clarté d'enseignante, dans la fidélité à la kénose miséricordieuse du Christ. La vérité s'incarne dans la fragilité humaine non pour la condamner, mais pour la sauver. »Un livre essentiel pour comprendre combien il est urgent de sauvegarder la famille.

« La famille est importante, elle est nécessaire pour la survie de l'humanité. S'il n'y a pas de famille, la survie culturelle de l'humanité est en danger. Que cela nous plaise ou non, la famille est la base. » C'est ce que disait le pape François à la radio de l'archidiocèse de Rio de Janeiro, le 27 juillet 2013.En regardant la famille dans la réalité de sa beauté et l'appel de Dieu concernant notamment la vie conjugale, l'auteur, à la suite du synode sur la famille en octobre 2014 à Rome, insiste sur l'importance de la conversion de l'Église pour la famille qui ne doit pas être une pastorale comme une autre.La pastorale de la famille doit devenir une urgence de la « nouvelle évangélisation ». Le synode le dit exactement : « L'annonce de l'Évangile de la famille constitue une urgence pour la nouvelle évangélisation. L'Église est appelée à le mettre en pratique, avec une tendresse de mère et une clarté d'enseignante, dans la fidélité à la kénose miséricordieuse du Christ. La vérité s'incarne dans la fragilité humaine non pour la condamner, mais pour la sauver. »Un livre essentiel pour comprendre combien il est urgent de sauvegarder la famille.

Aujourd'hui, dans l'Église Catholique Romaine, des nouvelles formes de communautés « associatives » émergent et posent un certain nombre de questions au regard du droit canonique. L'une d'entre elles concerne les personnes qui font le choix du célibat, comme signe d'une « consécration » dans ces nouvelles formes communautaire. En droit public français, des interrogations naissent aussi au sujet de ces nouvelles formes de vie consacrée : certaines d'entre elles acquièrent un statut d'association publique internationale en droit canonique, et demandent, par exemple, leur reconnaissance légale comme « congrégation religieuse » (notamment, quant à la sécurité sociale, au droit du travail, et d'autres encore) avec le statut congréganiste.Ce sont ces critères essentiels de « reconnaissance » que cette étude se propose de préciser, comme la profession des conseils évangéliques, les liens sacrés, la stabilité, une vie fraternelle, une soumission à une règle de vie approuvée. Il s'agit de manifester plus clairement l'état de vie consacrée dans ces mouvements qui attendent, pour une part, une certaine reconnaissance de la part de l'Église, sans compter les contentieux, relativement nombreux, relatifs notamment aux régimes de sécurité sociale et de retraites, devant les juridictions étatiques.Cédric Burgun est prêtre incardiné au diocèse de Metz, membre de la Communauté de l'Emmanuel. Il est enseignant-chercheur à temps plein à la Faculté de Droit Canonique à l'Institut Catholique de Paris.

Objective: The Learning Health System (LHS) requires integration of research into routine practice. eSource or embedding clinical trial functionalities into routine electronic health record (EHR) systems has long been put forward as a solution to the rising costs of research. We aimed to create and validate an eSource solution that would be readily extensible as part of a LHS. Materials and Methods: The EU FP7 TRANSFoRm project's approach is based on dual modelling, using the Clinical Research Information Model (CRIM) and the Clinical Data Integration Model of meaning (CDIM) to bridge the gap between clinical and research data structures, using the CDISC Operational Data Model (ODM) standard. Validation against GCP requirements was conducted in a clinical site, and a cluster randomised evaluation by site nested into a live clinical trial. Results: Using the form definition element of ODM, we linked precisely modelled data queries to data elements, constrained against CDIM concepts, to enable automated patient identification for specific protocols and prepopulation of electronic case report forms (e-CRF). Both control and eSource sites recruited better than expected with no significant difference. Completeness of clinical forms was significantly improved by eSource, but Patient Related Outcome Measures (PROMs) were less well completed on smartphones than paper in this population. Discussion: The TRANSFoRm approach provides an ontologically-based approach to eSource in a low-resource, heterogeneous, highly distributed environment, that allows precise prospective mapping of data elements in the EHR. Conclusion: Further studies using this approach to CDISC should optimise the delivery of PROMS, whilst building a sustainable infrastructure for eSource with research networks, trials units and EHR vendors.

Introduction: This article is part of the Focus Theme of Methods of Information in Medicine on "Managing Interoperability and Complexity in Health Systems". Background: Primary care data is the single richest source of routine health care data. However its use, both in research and clinical work, often requires data from multiple clinical sites, clinical trials databases and registries. Data integration and interoperability are therefore of utmost importance. Objectives: TRANSFoRm's general approach relies on a unified interoperability frame-work, described in a previous paper. We developed a core ontology for an interoperability framework based on data mediation. This article presents how such an ontology, the Clinical Data Integration Model (CDIM), can be designed to support, in conjunction with appropriate terminologies, biomedical data federation within TRANSFoRm, an EU FP7 project that aims to develop the digital infrastructure for a learning healthcare system in European Primary Care. Methods: TRANSFoRm utilizes a unified structural /terminological interoperability framework, based on the local-as-view mediation paradigm. Such an approach mandates the global information model to describe the domain of interest independently of the data sources to be explored. Following a requirement analysis process, no ontology focusing on primary care research was identified and, thus we designed a realist ontology based on Basic Formal Ontology to support our framework in collaboration with various terminologies used in primary care. Results: The resulting ontology has 549 classes and 82 object properties and is used to support data integration for TRANSFoRm's use cases. Concepts identified by researchers were successfully expressed in queries using CDIM and pertinent terminologies. As an example, we illustrate how, in TRANSFoRm, the Query Formulation Workbench can capture eligibility criteria in a computable representation, which is based on CDIM. Conclusion: A unified med

We investigate how probabilities can be assigned to dispositions in ontologies, building on Popper's propensity approach. We show that if D is a disposition universal associated with a trigger T and a realization R, and d is an instance of D, then one can assign a probability to the triplets (d,T,R) and (D,T,R). These probabilities measure the causal power of dispositions, which can be defined as limits of relative frequencies of possible instances of T triggering an instance of R over a hypothetical infinite random sequence of possible instances of T satisfying certain conditions. Adopting a fallibilist methodology, these probability values can be estimated by relative frequencies in actual finite sequences., QC 20131011

After a summary of the statutory order of the French Bureau of Mines, two inspection methods are described: inspection by sight, and magnetic checking. A combination of the two methods is recommended., After a summary of the statutory order of the French Bureau of Mines, two inspection methods are described: inspection by sight, and magnetic checking. A combination of the two methods is recommended.

Site-selective organic transformations are commonly required in the synthesis of complex molecules. By employing a bespoke metal-organic framework (MOF, 1·[Mn(CO)3N3]), in which coordinated azide anions are precisely positioned within 1D channels, we present a strategy for the site-selective transformation of dialkynes into alkyne-functionalized triazoles. As an illustration of this approach, 1,7-octadiyne-3,6-dione stoichiometrically furnishes the mono-“click” product N-methyl-4-hex-5’-ynl-1’,4’dione-1,2,3-triazole with only trace bis-triazole side-product. Stepwise insights into conversions of the MOF reaction vessel were obtained by X-ray crystallography, demonstrating that the reactive sites are “isolated” from one another. Single-crystal to singlecrystal transformations of the Mn(I)-metalated material 1·[Mn(CO)3(H2O)]Br to the corresponding azide species 1·[Mn(CO)3N3] with sodium azide, followed by a series of [3+2] azide-alkyne cycloaddition reactions, are reported. The final liberation of the “click” products from the porous material is achieved by N-alkylation with MeBr, regenerating starting MOF 1·[Mn(CO)3(H2O)]Br, and the organic products characterized by NMR spectroscopy and mass spectrometry. Once the dialkyne length exceeds the azide separation, site selectivity is lost, confirming the critical importance of isolated azide moieties for this strategy. We postulate that carefully designed MOFs can act as physical protecting groups to facilitate other site-selective and chemoselective transformations.

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Site-selective organic transformations are commonly required in the synthesis of complex molecules. By employing a bespoke metal-organic framework (MOF, 1·[Mn(CO)3N3]), in which coordinated azide anions are precisely positioned within 1D channels, we present a strategy for the site-selective transformation of dialkynes into alkyne-functionalized triazoles. As an illustration of this approach, 1,7-octadiyne-3,6-dione stoichiometrically furnishes the mono-“click” product N-methyl-4-hex-5’-ynl-1’,4’dione-1,2,3-triazole with only trace bis-triazole side-product. Stepwise insights into conversions of the MOF reaction vessel were obtained by X-ray crystallography, demonstrating that the reactive sites are “isolated” from one another. Single-crystal to singlecrystal transformations of the Mn(I)-metalated material 1·[Mn(CO)3(H2O)]Br to the corresponding azide species 1·[Mn(CO)3N3] with sodium azide, followed by a series of [3+2] azide-alkyne cycloaddition reactions, are reported. The final liberation of the “click” products from the porous material is achieved by N-alkylation with MeBr, regenerating starting MOF 1·[Mn(CO)3(H2O)]Br, and the organic products characterized by NMR spectroscopy and mass spectrometry. Once the dialkyne length exceeds the azide separation, site selectivity is lost, confirming the critical importance of isolated azide moieties for this strategy. We postulate that carefully designed MOFs can act as physical protecting groups to facilitate other site-selective and chemoselective transformations.

Site-selective organic transformations are commonly required in the synthesis of complex molecules. By employing a bespoke metal-organic framework (MOF, 1·[Mn(CO)3N3]), in which coordinated azide anions are precisely positioned within 1D channels, we present a strategy for the site-selective transformation of dialkynes into alkyne-functionalized triazoles. As an illustration of this approach, 1,7-octadiyne-3,6-dione stoichiometrically furnishes the mono-“click” product N-methyl-4-hex-5’-ynl-1’,4’dione-1,2,3-triazole with only trace bis-triazole side-product. Stepwise insights into conversions of the MOF reaction vessel were obtained by X-ray crystallography, demonstrating that the reactive sites are “isolated” from one another. Single-crystal to singlecrystal transformations of the Mn(I)-metalated material 1·[Mn(CO)3(H2O)]Br to the corresponding azide species 1·[Mn(CO)3N3] with sodium azide, followed by a series of [3+2] azide-alkyne cycloaddition reactions, are reported. The final liberation of the “click” products from the porous material is achieved by N-alkylation with MeBr, regenerating starting MOF 1·[Mn(CO)3(H2O)]Br, and the organic products characterized by NMR spectroscopy and mass spectrometry. Once the dialkyne length exceeds the azide separation, site selectivity is lost, confirming the critical importance of isolated azide moieties for this strategy. We postulate that carefully designed MOFs can act as physical protecting groups to facilitate other site-selective and chemoselective transformations.

Site-selective organic transformations are commonly required in the synthesis of complex molecules. By employing a bespoke metal-organic framework (MOF, 1·[Mn(CO)3N3]), in which coordinated azide anions are precisely positioned within 1D channels, we present a strategy for the site-selective transformation of dialkynes into alkyne-functionalized triazoles. As an illustration of this approach, 1,7-octadiyne-3,6-dione stoichiometrically furnishes the mono-“click” product N-methyl-4-hex-5’-ynl-1’,4’dione-1,2,3-triazole with only trace bis-triazole side-product. Stepwise insights into conversions of the MOF reaction vessel were obtained by X-ray crystallography, demonstrating that the reactive sites are “isolated” from one another. Single-crystal to singlecrystal transformations of the Mn(I)-metalated material 1·[Mn(CO)3(H2O)]Br to the corresponding azide species 1·[Mn(CO)3N3] with sodium azide, followed by a series of [3+2] azide-alkyne cycloaddition reactions, are reported. The final liberation of the “click” products from the porous material is achieved by N-alkylation with MeBr, regenerating starting MOF 1·[Mn(CO)3(H2O)]Br, and the organic products characterized by NMR spectroscopy and mass spectrometry. Once the dialkyne length exceeds the azide separation, site selectivity is lost, confirming the critical importance of isolated azide moieties for this strategy. We postulate that carefully designed MOFs can act as physical protecting groups to facilitate other site-selective and chemoselective transformations.