Reuse of safety certification artefacts across standards and domains: A systematic approach

Reuse of systems and subsystem is a common practice in safety-critical systems engineering. Reuse can improve system development and assurance, and there are recommendations on reuse for some domains. Cross-domain reuse, in which a previously certified product typically needs to be assessed against different safety standards, has however received little attention. No guidance exists for this reuse scenario despite its relevance in industry, thus practitioners need new means to tackle it. This paper aims to fill this gap by presenting a systematic approach for reuse of safety certification artefacts across standards and domains. The approach is based on the analysis of the similarities and on the specification of maps between standards. These maps are used to determine the safety certification artefacts that can be reused from one domain to another and reuse consequences. The approach has been validated with practitioners in a case study on the reuse of an execution platform from railway to avionics. The results show that the approach can be effectively applied and that it can reduce the cost of safety certification across standards and domains. Therefore, the approach is a promising way of making cross-domain reuse more cost-effective in industry.European Commission's FP7 programm

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Safety of emapalumab in pediatric patients with primary hemophagocytic lymphohistiocytosis: findings from the primary analysis of the pivotal phase 2/3 study.

Primary hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening, immune regulatory disorder characterized by a hyperinflammatory state in which patients typically develop fever, splenomegaly, cytopenias and coagulopathy. In patients with primary HLH, the cytokine Interferon gamma (IFNy) is often markedly elevated and is considered a key contributor to the hyperinflammatory state. The treatment goal of primary HLH is to stabilize the disease by controlling the associated hyperinflammation in order to bring patients to transplantation, the only curative therapy. Current conventional therapy for HLH comprises immunochemotherapies, which are associated with opportunistic infections, toxicity, and high morbidity and mortality. Emapalumab is a fully human, anti-IFNy monoclonal antibody that neutralizes IFNy. It is approved by the FDA for the treatment of adult and pediatric patients with primary HLH with refractory, recurrent or progressive disease, or intolerance with conventional HLH therapy. Herein, we report on the safety of emapalumab in primary HLH seen in the pivotal phase 2/3 study and investigate the relationship of adverse events (AE) to dose and duration of treatment

Safety and Efficacy of Emapalumab in Pediatric Patients with Primary Hemophagocytic Lymphohistiocytosis

Phase II study on the use of emapalumab for therapy of HL