CONNECT: Emergent Connectors for Eternal Software Intensive Networked Systems

International audienceThe CONNECT Integrated Project aims at dropping the interoperability barrier by adopting a revolutionary approach to the seamless networking of digital systems, that is, synthesizing on the fly the connectors via which networked systems communicate. CONNECT enables the dynamic synthesis of CONNECTors by introducing a formal foundation for connectors, which allows learning, reasoning about and adapting the interaction behavior of networked systems

Development of a core outcome set for congenital pulmonary airway malformations : study protocol of an international Delphi survey

Introduction A worldwide lack of consensus exists on the optimal management of asymptomatic congenital pulmonary airway malformation (CPAM) even though the incidence is increasing. Either a surgical resection is performed or a wait-and-see policy is employed, depending on the treating physician. Management is largely based on expert opinion and scientific evidence is scarce. Wide variations in outcome measures are seen between studies making comparison difficult thus highlighting the lack of universal consensus in outcome measures as well. We aim to define a core outcome set which will include the most important core outcome parameters for paediatric patients with an asymptomatic CPAM. Methods and analysis This study will include a critical appraisal of the current literature followed by a three-stage Delphi process with two stakeholder groups. One surgical group including paediatric as well as thoracic surgeons, and a non-surgeon group including paediatric pulmonologists, intensive care and neonatal specialists. All participants will score outcome parameters according to their level of importance and the most important parameters will be determined by consensus. Ethics and dissemination Electronic informed consent will be obtained from all participants. Ethical approval is not required. After the core outcome set has been defined, we intend to design an international randomised controlled trial: the COllaborative Neonatal NEtwork for the first CPAM Trial, which will be aimed at determining the optimal management of patients with asymptomatic CPAM.Peer reviewe

Development of a core outcome set for congenital pulmonary airway malformations: study protocol of an international Delphi survey.

IntroductionA worldwide lack of consensus exists on the optimal management of asymptomatic congenital pulmonary airway malformation (CPAM) even though the incidence is increasing. Either a surgical resection is performed or a wait-and-see policy is employed, depending on the treating physician. Management is largely based on expert opinion and scientific evidence is scarce. Wide variations in outcome measures are seen between studies making comparison difficult thus highlighting the lack of universal consensus in outcome measures as well. We aim to define a core outcome set which will include the most important core outcome parameters for paediatric patients with an asymptomatic CPAM.Methods and analysisThis study will include a critical appraisal of the current literature followed by a three-stage Delphi process with two stakeholder groups. One surgical group including paediatric as well as thoracic surgeons, and a non-surgeon group including paediatric pulmonologists, intensive care and neonatal specialists. All participants will score outcome parameters according to their level of importance and the most important parameters will be determined by consensus.Ethics and disseminationElectronic informed consent will be obtained from all participants. Ethical approval is not required. After the core outcome set has been defined, we intend to design an international randomised controlled trial: the COllaborative Neonatal NEtwork for the first CPAM Trial, which will be aimed at determining the optimal management of patients with asymptomatic CPAM

Animal models to study cognitive impairment of chronic kidney disease

Mild cognitive impairment (MCI) is common in people with chronic kidney disease (CKD), and its prevalence increases with progressive loss of kidney function. MCI is characterized by a decline in cognitive performance greater than expected for an individual age and education level but with minimal impairment of instrumental activities of daily living. Deterioration can affect one or several cognitive domains (attention, memory, executive functions, language, and perceptual motor or social cognition). Given the increasing prevalence of kidney disease, more and more people with CKD will also develop MCI causing an enormous disease burden for these individuals, their relatives, and society. However, the underlying pathomechanisms are poorly understood, and current therapies mostly aim at supporting patients in their daily lives. This illustrates the urgent need to elucidate the pathogenesis and potential therapeutic targets and test novel therapies in appropriate preclinical models. Here, we will outline the necessary criteria for experimental modeling of cognitive disorders in CKD. We discuss the use of mice, rats, and zebrafish as model systems and present valuable techniques through which kidney function and cognitive impairment can be assessed in this setting. Our objective is to enable researchers to overcome hurdles and accelerate preclinical research aimed at improving the therapy of people with CKD and MCI

RD-Connect: an FP7 success story

Although individually uncommon, rare diseases (RDs) collectively affect 6-8% of the population; around 30M people in the EU and 400M worldwide. RD research faces specific challenges. Since patients, clinical expertise and research communities are scarce and fragmented, data sharing between researchers is crucial. To address this, in 2012 the European Commission awarded a €12M FP7 grant to RD-Connect to create an infrastructure bringing together multiple data types used in RD research into a common resource for researchers and clinicians. In six years, RD-Connect developed an integrated platform bringing together analysis tools and different types of data needed in RD research into a common resource for clinicians and researchers worldwide. The RD-Connect platform consists of three systems: Genome-Phenome Analysis Platform, Registry & Biobank Finder and Sample Catalogue, which are open to any RD. RD-Connect is open for data submissions and already holds thousands of datasets, including linked omics and phenotypic data, biosamples and information about RD patient registries and biobanks. The secure, pseudonymised datasets in RD-Connect are linked at an individual per-patient or per-sample level. Researchers can analyse data, find similar cases and related information such as availability of biomaterials. Thanks to the work on data linkage, patient registries and biobanks receive support in making their datasets Findable, Accessible, Interoperable and Reusable (FAIR). Successful collaborations with several partner projects, including NeurOmics, EURenOmics and BBMRI-LPC, led to the discovery of over 100 novel disease genes. In addition, RD-Connect has developed a number of clinical bioinformatic tools that facilitate data analysis and interpretation and are integrated in the Platform. RD-Connect ethical and legal experts developed guidelines for researchers and optimal models for data sharing, while the engagement of patients and patient representatives at every level of the project’s work ensured patient-centred approach. Collaboration with the European Reference Networks will ensure the impact of RD-Connect on improving RD patients’ quality of life. RD-Connect is embedded in European and international efforts, including BBMRI, ELIXIR and the International Rare Disease Research Consortium (IRDiRC). The project has helped move the field forward by advancing omics research and data sharing and is thus an EU flagship project and an FP7 success story.</p

RD-Connect: an integrated infrastructure for data sharing and analysis in rare disease research

RD-Connect is an infrastructure for rare disease research bringing together multiple data types in three systems: Genome-Phenome Analysis Platform (platform.rd-connect.eu), Sample Catalogue (samples.rd-connect.eu) and Registry & Biobank Finder (catalogue.rd-connect.eu). All these systems are open to any rare disease and available free of charge. The Genome-Phenome Analysis Platform is a centralized data repository and a user-friendly online analysis system combining omics data (genomics, proteomics, transcriptomics) with clinical information at individual-patient, family or cohort level. Whole-genome, exome and gene panel datasets are submitted by the end-user and processed by RD-Connect's standardised analysis and annotation pipeline to make data from different sequencing providers comparable. Raw data is deposited at the European Genome-phenome Archive (EGA) for long-term storage. Clinical information is recorded in the PhenoTips system, which simplifies entry of clinical data using the Human Phenotype Ontology. Results are available to the submitter and authorised users through the highly configurable platform, which enables advanced filtering and prioritization of variants. Users can analyse their own patients and compare results with other submitted cohorts, including queries such as: “Does this variant exist in this cohort?” and “Are there patients in other databases with matching phenotype and candidate variant in the same gene?”. The Platform already includes thousands of datasets from partner projects such as NeurOmics (www.rd-neuromics.eu) and BBMRI-LPC (www.bbmri-lpc.org). In 2018, it became the primary data sharing and analysis platform for the new Solve-RD project, which will bring in 19,000 unsolved cases from European Reference Networks over 5 years. RD-Connect is free and open for contributions from individual research groups and other projects: contact [email protected]. The Sample Catalogue allows browsing biosample collections stored in rare disease biobanks using powerful filtering functions. It provides detailed information about individual biosamples, including disease, diagnosis type, sample type, sex, availability of genetic and registry data and of samples from the patient’s relatives. Currently, the Sample Catalogue includes over 25,000 samples stored by rare disease biobanks in the EuroBioBank Network. The work is ongoing to make the Sample Catalogue interconnected with the Platform, to enable finding biosamples from patients with a specific genetic variant, and with the Registry & Biobank Finder, to allow direct link from the global directory of rare disease databases to the sample collections.</p

The CONNECT project: Combining macro- and micro-structure

AbstractIn recent years, diffusion MRI has become an extremely important tool for studying the morphology of living brain tissue, as it provides unique insights into both its macrostructure and microstructure. Recent applications of diffusion MRI aimed to characterize the structural connectome using tractography to infer connectivity between brain regions. In parallel to the development of tractography, additional diffusion MRI based frameworks (CHARMED, AxCaliber, ActiveAx) were developed enabling the extraction of a multitude of micro-structural parameters (axon diameter distribution, mean axonal diameter and axonal density). This unique insight into both tissue microstructure and connectivity has enormous potential value in understanding the structure and organization of the brain as well as providing unique insights to abnormalities that underpin disease states.The CONNECT (Consortium Of Neuroimagers for the Non-invasive Exploration of brain Connectivity and Tracts) project aimed to combine tractography and micro-structural measures of the living human brain in order to obtain a better estimate of the connectome, while also striving to extend validation of these measurements. This paper summarizes the project and describes the perspective of using micro-structural measures to study the connectome

MRI Features and Their Association With Outcomes in Children With Anti-NMDA Receptor Encephalitis

OBJECTIVES: How brain MRI lesions associate with outcomes in pediatric anti-NMDA receptor encephalitis (pNMDARE) is unknown. In this study, we correlate T2-hyperintense MRI brain lesions with clinical outcomes in pNMDARE. METHODS: This was a multicenter retrospective cohort study from 11 institutions. Children younger than 18 years with pNMDARE were included. One-year outcomes were assessed by the modified Rankin Score (mRS) with good (mRS ≤2) and poor (mRS ≥3) outcomes. RESULTS: A total of 175 pNMDARE subjects were included, with 1-year mRS available in 142/175 (81%) and 60/175 (34%) had abnormal brain MRIs. The most common T2-hyperintense lesion locations were frontal, temporal, and parietal. MRI features that predicted poor 1-year outcomes included abnormal MRI, particularly T2 lesions in the frontal and occipital lobes. After adjusting for treatment within 4 weeks of onset, improvement within 4 weeks, and intensive care unit admission, MRI features were no longer associated with poor outcomes, but after multiple imputation for missing data, T2 frontal and occipital lesions associated with poor outcomes. DISCUSSION: Abnormal frontal and occipital lesions on MRI may associate with 1-year mRS in pNMDARE. MRI of the brain may be a helpful prognostication tool that should be examined in future studies