Global patterns in monthly activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus: a systematic analysis

Background Influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus are the most common viruses associated with acute lower respiratory infections in young children (= 65 years). A global report of the monthly activity of these viruses is needed to inform public health strategies and programmes for their control.Methods In this systematic analysis, we compiled data from a systematic literature review of studies published between Jan 1, 2000, and Dec 31, 2017; online datasets; and unpublished research data. Studies were eligible for inclusion if they reported laboratory-confirmed incidence data of human infection of influenza virus, respiratory syncytial virus, parainfluenza virus, or metapneumovirus, or a combination of these, for at least 12 consecutive months (or 52 weeks equivalent); stable testing practice throughout all years reported; virus results among residents in well-defined geographical locations; and aggregated virus results at least on a monthly basis. Data were extracted through a three-stage process, from which we calculated monthly annual average percentage (AAP) as the relative strength of virus activity. We defined duration of epidemics as the minimum number of months to account for 75% of annual positive samples, with each component month defined as an epidemic month. Furthermore, we modelled monthly AAP of influenza virus and respiratory syncytial virus using site-specific temperature and relative humidity for the prediction of local average epidemic months. We also predicted global epidemic months of influenza virus and respiratory syncytial virus on a 5 degrees by 5 degrees grid. The systematic review in this study is registered with PROSPERO, number CRD42018091628.Findings We initally identified 37 335 eligible studies. Of 21 065 studies remaining after exclusion of duplicates, 1081 full-text articles were assessed for eligibility, of which 185 were identified as eligible. We included 246 sites for influenza virus, 183 sites for respiratory syncytial virus, 83 sites for parainfluenza virus, and 65 sites for metapneumovirus. Influenza virus had clear seasonal epidemics in winter months in most temperate sites but timing of epidemics was more variable and less seasonal with decreasing distance from the equator. Unlike influenza virus, respiratory syncytial virus had clear seasonal epidemics in both temperate and tropical regions, starting in late summer months in the tropics of each hemisphere, reaching most temperate sites in winter months. In most temperate sites, influenza virus epidemics occurred later than respiratory syncytial virus (by 0.3 months [95% CI -0.3 to 0.9]) while no clear temporal order was observed in the tropics. Parainfluenza virus epidemics were found mostly in spring and early summer months in each hemisphere. Metapneumovirus epidemics occurred in late winter and spring in most temperate sites but the timing of epidemics was more diverse in the tropics. Influenza virus epidemics had shorter duration (3.8 months [3.6 to 4.0]) in temperate sites and longer duration (5.2 months [4.9 to 5.5]) in the tropics. Duration of epidemics was similar across all sites for respiratory syncytial virus (4.6 months [4.3 to 4.8]), as it was for metapneumovirus (4.8 months [4.4 to 5.1]). By comparison, parainfluenza virus had longer duration of epidemics (6.3 months [6.0 to 6.7]). Our model had good predictability in the average epidemic months of influenza virus in temperate regions and respiratory syncytial virus in both temperate and tropical regions. Through leave-one-out cross validation, the overall prediction error in the onset of epidemics was within 1 month (influenza virus -0.2 months [-0.6 to 0.1]; respiratory syncytial virus 0.1 months [-0.2 to 0.4]).Interpretation This study is the first to provide global representations of month-by-month activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus. Our model is helpful in predicting the local onset month of influenza virus and respiratory syncytial virus epidemics. The seasonality information has important implications for health services planning, the timing of respiratory syncytial virus passive prophylaxis, and the strategy of influenza virus and future respiratory syncytial virus vaccination. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd

Modular Interpreters For The Masses: Implicit Context Propagation Using Object Algebras

International audienceModular interpreters have the potential to achieve component-based language development: instead of writing language interpreters from scratch, they can be assembled from reusable, semantic building blocks. Unfortunately, traditional language interpreters are hard to extend because different language constructs may require different interpreter signatures. For instance, arithmetic interpreters produce a value without any context information, whereas binding constructs require an additional environment. In this paper, we present a practical solution to this problem based on implicit context propagation. By structuring denotational-style interpreters as Object Algebras, base interpreters can be retroactively lifted into new interpreters that have an extended signature. The additional parameters are implicitly propagated behind the scenes, through the evaluation of the base interpreter. Interpreter lifting enables a flexible style of component-based language development. The technique works in mainstream object-oriented languages, does not sacrifice type safety or separate compilation, and can be easily automated. We illustrate implicit context propagation using a modular definition of Featherweight Java and its extension to support side-effects

On the evolution of iMedia implementations

With the advent of iMedia, the traditional content component was extended with a behavioral component (i.e. software). The development of this behavioral component using traditional software development techniques is cumbersome because of the extreme deadlines and extremely short time-to-market situation. We propose a new development approach that provides the media producer with sufficient control to define and change the product in very short time frames. The system is based on existing technologies like generative programming, transformation systems and domain engineering. Since the iMedia domain is in continuous flux, and these technologies are mostly designed for stable domains, the evolution of the implementation was a crucial problem hampering its successful application. Solutions and mechanisms are presented that ameliorate the modularity and consequently the evolution. 1

Language boxes: Bending the host language with modular language changes

Abstract. As domain-specific modeling begins to attract widespread acceptance, pressure is increasing for the development of new domainspecific languages. Unfortunately these DSLs typically conflict with the grammar of the host language, making it difficult to compose hybrid code except at the level of strings; few mechanisms (if any) exist to control the scope of usage of multiple DSLs; and, most seriously, existing host language tools are typically unaware of the DSL extensions, thus hampering the development process. Language boxes address these issues by offering a simple, modular mechanism to encapsulate (i) compositional changes to the host language, (ii) transformations to address various concerns such as compilation and syntax highlighting, and (iii) scoping rules to control visibility of fine-grained language extensions. We describe the design and implementation of language boxes, and show with the help of several examples how modular extensions can be introduced to a host language and environment.

Reverse-engineering reusable language modules from legacy domain-specific languages

International audienceThe use of domain-specific languages (DSLs) has become a successful technique in the development of complex systems. Nevertheless , the construction of this type of languages is time-consuming and requires highly-specialized knowledge and skills. An emerging practice to facilitate this task is to enable reuse through the definition of language modules which can be later put together to build up new DSLs. Still, the identification and definition of language modules are complex and error-prone activities, thus hindering the reuse exploitation when developing DSLs. In this paper, we propose a computer-aided approach to i) identify potential reuse in a set of legacy DSLs; and ii) capitalize such potential reuse by extracting a set of reusable language modules with well defined interfaces that facilitate their assembly. We validate our approach by using realistic DSLs coming out from industrial case studies and obtained from public GitHub repositories

Human T lymphocyte priming in vitro by haptenated autologous dendritic cells

Dendritic cells (DC), generated from adherent peripheral blood mononuclear cells (PBMC) by culturing with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4, were used to study in vitro sensitization of naive, hapten-specific T cells and to analyse cross-reactivities to related compounds. DC were hapten-derivatized with nickel sulphate (Ni) or 2-hydroxyethyl-methacrylate (HEMA), followed by tumour necrosis factor-alpha (TNF-α)-induced maturation, before autologous T cells and a cytokine cocktail of IL-1β, IL-2 and IL-7 were added. After T cell priming for 7 days, wells were split and challenged for another 7 days with Ni or HEMA, and potentially cross-reactive haptens. Hapten-specificity of in vitro priming was demonstrated by proliferative responses to the haptens used for priming but not to the unrelated haptens. Highest priming efficiencies were obtained when both IL-4 and IL-12 were added to the cytokine supplement. Marked interferon-gamma (IFN-γ) release (up to 4 ng/ml) was found when IL-12 was included in the cultures, whereas IL-5 release (up to 500 pg/ml) was observed after addition of IL-4 alone, or in combination with IL-12. Nickel-primed T cells showed frequent cross-reactivities with other metals closely positioned in the periodic table, i.e. palladium and copper, whereas HEMA-primed T cells showed distinct cross-reactivities with selected methacrylate congeners. Similar cross-reactivities are known to occur in allergic patients. Thus, in vitro T cell priming provides a promising tool for studying factors regulating cytokine synthesis, and cross-reactivity patterns of hapten-specific T cells