An ontological foundation for ocular phenotypes and rare eye diseases.

BACKGROUND: The optical accessibility of the eye and technological advances in ophthalmic diagnostics have put ophthalmology at the forefront of data-driven medicine. The focus of this study is rare eye disorders, a group of conditions whose clinical heterogeneity and geographic dispersion make data-driven, evidence-based practice particularly challenging. Inter-institutional collaboration and information sharing is crucial but the lack of standardised terminology poses an important barrier. Ontologies are computational tools that include sets of vocabulary terms arranged in hierarchical structures. They can be used to provide robust terminology standards and to enhance data interoperability. Here, we discuss the development of the ophthalmology-related component of two well-established biomedical ontologies, the Human Phenotype Ontology (HPO; includes signs, symptoms and investigation findings) and the Orphanet Rare Disease Ontology (ORDO; includes rare disease nomenclature/nosology). METHODS: A variety of approaches were used including automated matching to existing resources and extensive manual curation. To achieve the latter, a study group including clinicians, patient representatives and ontology developers from 17 countries was formed. A broad range of terms was discussed and validated during a dedicated workshop attended by 60 members of the group. RESULTS: A comprehensive, structured and well-defined set of terms has been agreed on including 1106 terms relating to ocular phenotypes (HPO) and 1202 terms relating to rare eye disease nomenclature (ORDO). These terms and their relevant annotations can be accessed in http://www.human-phenotype-ontology.org/ and http://www.orpha.net/ ; comments, corrections, suggestions and requests for new terms can be made through these websites. This is an ongoing, community-driven endeavour and both HPO and ORDO are regularly updated. CONCLUSIONS: To our knowledge, this is the first effort of such scale to provide terminology standards for the rare eye disease community. We hope that this work will not only improve coding and standardise information exchange in clinical care and research, but also it will catalyse the transition to an evidence-based precision ophthalmology paradigm

An ontological foundation for ocular phenotypes and rare eye diseases.

BACKGROUND: The optical accessibility of the eye and technological advances in ophthalmic diagnostics have put ophthalmology at the forefront of data-driven medicine. The focus of this study is rare eye disorders, a group of conditions whose clinical heterogeneity and geographic dispersion make data-driven, evidence-based practice particularly challenging. Inter-institutional collaboration and information sharing is crucial but the lack of standardised terminology poses an important barrier. Ontologies are computational tools that include sets of vocabulary terms arranged in hierarchical structures. They can be used to provide robust terminology standards and to enhance data interoperability. Here, we discuss the development of the ophthalmology-related component of two well-established biomedical ontologies, the Human Phenotype Ontology (HPO; includes signs, symptoms and investigation findings) and the Orphanet Rare Disease Ontology (ORDO; includes rare disease nomenclature/nosology). METHODS: A variety of approaches were used including automated matching to existing resources and extensive manual curation. To achieve the latter, a study group including clinicians, patient representatives and ontology developers from 17 countries was formed. A broad range of terms was discussed and validated during a dedicated workshop attended by 60 members of the group. RESULTS: A comprehensive, structured and well-defined set of terms has been agreed on including 1106 terms relating to ocular phenotypes (HPO) and 1202 terms relating to rare eye disease nomenclature (ORDO). These terms and their relevant annotations can be accessed in http://www.human-phenotype-ontology.org/ and http://www.orpha.net/ ; comments, corrections, suggestions and requests for new terms can be made through these websites. This is an ongoing, community-driven endeavour and both HPO and ORDO are regularly updated. CONCLUSIONS: To our knowledge, this is the first effort of such scale to provide terminology standards for the rare eye disease community. We hope that this work will not only improve coding and standardise information exchange in clinical care and research, but also it will catalyse the transition to an evidence-based precision ophthalmology paradigm

The need for widely available genomic testing in rare eye diseases: an ERN-EYE position statement.

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

Expansion of the Human Phenotype Ontology (HPO) knowledge base and resources.

The Human Phenotype Ontology (HPO)-a standardized vocabulary of phenotypic abnormalities associated with 7000+ diseases-is used by thousands of researchers, clinicians, informaticians and electronic health record systems around the world. Its detailed descriptions of clinical abnormalities and computable disease definitions have made HPO the de facto standard for deep phenotyping in the field of rare disease. The HPO\u27s interoperability with other ontologies has enabled it to be used to improve diagnostic accuracy by incorporating model organism data. It also plays a key role in the popular Exomiser tool, which identifies potential disease-causing variants from whole-exome or whole-genome sequencing data. Since the HPO was first introduced in 2008, its users have become both more numerous and more diverse. To meet these emerging needs, the project has added new content, language translations, mappings and computational tooling, as well as integrations with external community data. The HPO continues to collaborate with clinical adopters to improve specific areas of the ontology and extend standardized disease descriptions. The newly redesigned HPO website (www.human-phenotype-ontology.org) simplifies browsing terms and exploring clinical features, diseases, and human genes

Immune response under heparin treatment : studies about roles of heparin structure and protamine sulphate

La réponse immune sous héparine (H) est associée à la synthèse d’anticorps (Ac) d’isotype IgG dirigés contre le facteur plaquettaire 4 (FP4) modifié par l’héparine. Ces anticorps se fixent par leur fragment Fc aux récepteurs FcγRIIa des plaquettes et induisent une forte activation plaquettaire. Les héparines de bas poids moléculaire sont constituées d’un mélange hétérogène d’oligosaccharides (OS) dont la structure varie en fonction de leur nombre de sucres et de groupements sulfates. Nous avons montré que seuls les OS ayant dix groupements sulfates ou plus, peuvent modifier le FP4 et permettre la fixation des Ac héparine-dépendants. La chirurgie cardiaque est associée à une forte activation plaquettaire et les patients sont exposés à de fortes concentrations d’héparine qui est neutralisée en fin d’intervention par le sulfate de protamine (SP). Alors que 30 à 50 % d’entre eux développent des Ac anti H/FP4 nous avons montré que 25% développent également des Ac dirigés contre les complexes H/SP et que ces Ac sont capables in vitro d’induire une activation plaquettaire. Le rôle de ces Ac in vivo reste cependant discuté.The immune response under heparin (H) treatment is associated with IgG antibodies (Abs) synthesis against heparin-modified Platelet Factor 4 (PF4). These Abs bind FcγRIIa receptors via their Fc fragment and promote strong platelet activation. Low Molecular Weight Heparins are complex mixtures of polysaccharide fragments. These oligosaccharides (OS) have a variable structure due to variations in the type of sugar units and the number of sulphate groups. We demonstrated that OS longer than 10 saccharides and with a large number of sulphate groups are likely able to modify PF4 and allow the binding of heparin-dependent Abs. Cardiac surgery is associated with strong platelet activation and high doses of unfractionated heparin are administered to patients during surgery, and then neutralized with protamine sulfate (SP) at the end of the intervention. 30 to 50% of patients develop anti H/PF4 Abs, but we demonstrated that 25% do synthethized anti H/SP Abs able to activate platelets in vitro. The pathogenic role of these Abs to H/SP in vivo is controversial

Risque de thromboses veineuses associé à la prise d'acétate de cyprotérone

TOURS-BU Sciences Pharmacie (372612104) / SudocSudocFranceF

Fixation des anticorps héparine-dépendants au facteur plaquettaire 4 modifié par des oligosaccharides isolés de l'énoxaparine (étude en résonnance plasmonique de surface et par un test d'activation plaquettaire)

TOURS-BU Sciences Pharmacie (372612104) / SudocSudocFranceF

Reconstructing the fallen arch of Notre-Dame. New insights into Gothic vault-building

International audienceDuring the fire in April 2019, part of the central vaulting of the nave of Notre-Dame deParis collapsed beneath the impact of the fallen spire. The blocks composing thetransverse arch were decontaminated, then subjected to archaeological examinationprior to attempting to dry-mount them (i.e., without mortar) on the ground. The purposewas to collect as much information as possible about the arch itself (its state ofconservation, geometry, fashioning of the blocks, assembly, etc.), to consider thepossibility of putting the fallen stones back in their original places, and more broadly toimprove knowledge about mediaeval cathedral vaulting.This article describes the method used during this mounting, which took place in winter2020/21. Five criteria of differing kind and importance guided decisions on where toplace the voussoirs, which way round to position them, and which to associate withwhich. Three were taken into consideration from the outset, with the interpretation oftwo of these changing over time: the non-standardized dimension of the voussoirs(their thickness), the presence of a cross mark on one of the joint faces, and thepresence of rectangular notches on the extrados of the blocks for housing the end of acentering system for constructing the vault compartments. Two other criteria wereincorporated as work progressed, pertaining to the order in which the blocks werecollected after the fire, and the geological facies of the stones, thus introducing the ideaof degree of confidence.By the end of this operation, only four blocks had been placed with certainty.Nevertheless, the criteria thereby defined and their weighting may now be used as astarting point for other investigation methods. In terms of archaeology, the observationscarried out on this arch in these exceptional conditions suggest we should reconsiderthe dating of the nave vaulting, while throwing light more broadly on the relativechronology of building works on this landmark monument of Gothic architecture

Evaluation par résonnance plasmonique de surface et par le test de libération de sérotonine radiomarquée de la fixation d'anticorps héparine-dépendants au facteur plaquettaire 4 modifié par des oligosaccharides isolés de l'énoxaparine

National audienc