Incidence and outcome of acquired demyelinating syndromes in Dutch children: update of a nationwide and prospective study

Introduction: Acquired demyelinating syndromes (ADS) are immune-mediated demyelinating disorders of the central nervous system in children. A nationwide, multicentre and prospective cohort study was initiated in the Netherlands in 2006, with a reported ADS incidence of 0.66/100,000 per year and MS incidence of 0.15/100,000 per year in the period between 2007 and 2010. In this study, we provide an update on the incidence and the long-term follow-up of ADS in the Netherlands. Methods: Children < 18 years with a first attack of demyelination were included consecutively from January 2006 to December 2016. Diagnoses were based on the International Paediatric MS study group consensus criteria. Outcome data were collected by neurological and neuropsychological assessments, and telephone call assessments. Results: Between 2011 and 2016, 55/165 of the ADS patients were diagnosed with MS (33%). This resulted in an increased ADS and MS incidence of 0.80/100,000 per year and 0.26/100,000 per year, respectively. Since 2006 a total of 243 ADS patients have been included. During follow-up (median 55 months, IQR 28–84), 137 patients were diagnosed with monophasic disease (56%), 89 with MS (37%) and 17 with multiphasic disease other than MS (7%). At least one form of residual deficit including cognitive impairment was observed in 69% of all ADS patients, even in monophasic ADS. An Expanded Disability Status Scale score of ≥ 5.5 was reached in 3/89 MS patients (3%). Conclusion: The reported incidence of ADS in Dutch children has increased since 2010. Residual deficits are common in this group, even in monophasic patients. Therefore, long-term follow-up in ADS patients is warranted

Infrastructure for Component-Based DDS Application Development

Enterprise distributed real-time and embedded (DRE) systems are increasingly being developed with the use of component-based software techniques. Unfortunately, commonly used component middleware platforms provide limited support for event-based publish/subscribe (pub/sub) mechanisms that meet both quality-ofservice (QoS) and configurability requirements of DRE systems. On the other hand, although pub/sub technologies, such as OMG Data Distribution Service (DDS), support a wide range of QoS settings, the level of abstraction they provide make it hard to configure them due to the significant source-level configuration that must be hard-coded at compile time or tailored at run-time using proprietary, ad hoc configuration logic. Moreover, developers of applications using native pub/sub technologies must write large amounts of boilerplate “glue ” code to support run-time configuration of QoS properties, which is tedious and error-prone. This paper describes a novel, generative approach that combines the strengths of QoS-enabled pub/sub middleware with component-based middleware technologies. In particular, this paper describes the design and implementation of DDS4CIAO which addresses a number of inherent and accidental complexities in the DDS4CCM standard. DDS4CIAO simplifies the development, deployment, and configuration of component-based DRE systems that leverage DDS’s powerful QoS capabilities by provisioning DDS QoS policy settings and simplifying the development of DDS applications

F6COM: A Component Model for Resource-Constrained and Dynamic Space-Based Computing Environment

Abstract—Component-based programming models are wellsuited to the design of large-scale, distributed applications because of the ease with which distributed functionality can be developed, deployed, and validated using the models ’ compositional properties. Existing component models supported by standardized technologies, such as the OMG’s CORBA Component Model (CCM), however, incur a number of limitations in the context of cyber physical systems (CPS) that operate in highly dynamic, resource-constrained, and uncertain environments, such as space environments, yet require multiple quality of service (QoS) assurances, such as timeliness, reliability, and security. To overcome these limitations, this paper presents the design of a novel component model called F6COM that is developed for applications operating in the context of a cluster of fractionated spacecraft. Although F6COM leverages the compositional capabilitie

Lethal respiratory failure and mild primary hypothyroidism in a term girl with a de novo heterozygous mutation in the TITF1/NKX2.1 gene.

CONTEXT: Thyroid transcription factor 1 (TITF1/NKX2.1) is expressed in the thyroid, lung, ventral forebrain, and pituitary. In the lung, TITF1/NKX2.1 activates the expression of genes critical for lung development and function. Titf/Nkx2.1(-/-) mice have pituitary and thyroid aplasia but also impairment of pulmonary branching. Humans with heterozygous TITF1/NKX2.1 mutations present with various combinations of primary hypothyroidism, respiratory distress, and neurological disorders. OBJECTIVE: The objective of the study was to report clinical and molecular studies of the first patient with lethal neonatal respiratory distress from a novel heterozygous TITF1/NKX2.1 mutation. Participant: This girl, the first child of healthy nonconsanguineous French-Canadian parents, was born at 41 wk. Birth weight was 3,460 g and Apgar scores were normal. Soon after birth, she developed acute respiratory failure with pulmonary hypertension. At neonatal screening on the second day of life, TSH was 31 mU/liter (N <15) and total T(4) 245 nmol/liter (N = 120-350). Despite mechanical ventilation, thyroxine, surfactant, and pulmonary vasodilators, the patient died on the 40th day. RESULTS: Histopathology revealed pulmonary tissue with low alveolar counts. The thyroid was normal. Sequencing of the patient's lymphocyte DNA revealed a novel heterozygous TITF1/NKX2.1 mutation (I207F). This mutation was not found in either parent. In vitro, the mutant TITF-1 had reduced DNA binding and transactivation capacity. CONCLUSION: This is the first reported case of a heterozygous TITF1/NKX2.1 mutation leading to neonatal death from respiratory failure. The association of severe unexplained respiratory distress in a term neonate with mild primary hypothyroidism is the clue that led to the diagnosis.Case ReportsJournal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

The Genome of the Netherlands: design, and project goals

Within the Netherlands a national network of biobanks has been established (Biobanking and Biomolecular Research Infrastructure-Netherlands (BBMRI-NL)) as a national node of the European BBMRI. One of the aims of BBMRI-NL is to enrich biobanks with different types of molecular and phenotype data. Here, we describe the Genome of the Netherlands (GoNL), one of the projects within BBMRI-NL. GoNL is a whole-genome-sequencing project in a representative sample consisting of 250 trio-families from all provinces in the Netherlands, which aims to characterize DNA sequence variation in the Dutch population. The parent-offspring trios include adult individuals ranging in age from 19 to 87 years (mean = 53 years; SD = 16 years) from birth cohorts 1910-1994. Sequencing was done on blood-derived DNA from uncultured cells and accomplished coverage was 14-15x. The family-based design represents a unique resource to assess the frequency of regional variants, accurately reconstruct haplotypes by family-based phasing, characterize short indels and complex structural variants, and establish the rate of de novo mutational events. GoNL will also serve as a reference panel for imputation in the available genome-wide association studies in Dutch and other cohorts to refine association signals and uncover population-specific variants. GoNL will create a catalog of human genetic variation in this sample that is uniquely characterized with respect to micro-geographic location and a wide range of phenotypes. The resource will be made available to the research and medical community to guide the interpretation of sequencing projects. The present paper summarizes the global characteristics of the project