An architecture and execution environment for component integration rules

The Integration Rules (IRules) project at Arizona State University (http://www.eas.asu.edu/~irules) is developing a declarative event-based approach to component integration. Integration rules are based on the concept of active database rules, providing an active approach for specifying event- driven activity in a distributed environment. The IRules project consists of a knowledge model that specifies the IRules Definition Language and an execution model that supports integration rule execution. This research focuses on the execution model and the architectural design parts of the IRules project. The main objective of this research is to develop a distributed execution environment for using integration rules in the integration of black-box components. In particular, this research will investigate the design of an architecture that supports the IRules semantic framework, the development of an execution model for rule and transaction processing, and the design of a rule processing algorithm for coordinating the execution of integration rules. This research will combine the distributed computing framework of Jini, the asynchronous event notification mechanism of the Java Message Service (JMS), and the distributed blocking access functionality of JavaSpaces to support active rule processing in a distributed environment. The limitations of the underlying Enterprise JavaBeans (EJB) component model pose transaction processing challenges for the integration process. This research will develop a suitable transaction model and processing logic to overcome the limitations of the underlying EJB component model. Furthermore, the architectural design will allow an easy extension of the system to accommodate other component models. This research is expected to contribute to nested rule and transaction processing for active rules that have not been previously addressed in distributed rule processing environments. The development of the IRules execution environment will also contribute to the use of distributed rule- based techniques for eventdriven component integration

Advanced Database Concepts for Undergraduates: Experience with Teaching a Second Course.

Abstract This paper describes the development of a second database course for undergraduates, preparing students for the advanced database concepts they will experience in industry. Assuming an introductory course on relational database systems as a prerequisite, the topics addressed in the course include object-oriented data modeling, objectoriented database systems, object-relational database systems, Web access to databases, and professionalism and ethics. We present our experience with teaching the course, elaborating on the topics and assignments. We also present feedback from students and industry partners as well as our own assessment of future course refinements

The development of the passé composé in lower-intermediate learners of French as a second language

In this study we tracked the development of the passe compose in second-language learners of French whose first language is English. Although the passe compose is a highly used tense among native speakers of French and it appears to present particular difficulty for first-language English speakers, its second-language development has been surprisingly under-researched. In order to trace developmental patterns of the passe compose we obtained a corpus of obligatory context use of this tense by 30 Year-12 (lower-intermediate) students at two time points six months apart and analysed the data both quantitatively and qualitatively. Our findings suggest that these students used remarkably few memorized formulas, that they passed through five distinct stages in their acquisition of the passe compose, that those early stages were characterized by transfer errors, and that the presence of the auxiliary, whether correct or incorrect, formed a crucial stage in the development of the tense. Theoretical explanations for the findings are presented together with some tentative pedagogical implications

NeuroML-DB: Sharing and characterizing data-driven neuroscience models described in NeuroML

As researchers develop computational models of neural systems with increasing sophistication and scale, it is often the case that fully de novo model development is impractical and inefficient. Thus arises a critical need to quickly find, evaluate, re-use, and build upon models and model components developed by other researchers. We introduce the NeuroML Database (NeuroML-DB.org), which has been developed to address this need and to complement other model sharing resources. NeuroML-DB stores over 1,500 previously published models of ion channels, cells, and networks that have been translated to the modular NeuroML model description language. The database also provides reciprocal links to other neuroscience model databases (ModelDB, Open Source Brain) as well as access to the original model publications (PubMed). These links along with Neuroscience Information Framework (NIF) search functionality provide deep integration with other neuroscience community modeling resources and greatly facilitate the task of finding suitable models for reuse. Serving as an intermediate language, NeuroML and its tooling ecosystem enable efficient translation of models to other popular simulator formats. The modular nature also enables efficient analysis of a large number of models and inspection of their properties. Search capabilities of the database, together with web-based, programmable online interfaces, allow the community of researchers to rapidly assess stored model electrophysiology, morphology, and computational complexity properties. We use these capabilities to perform a database-scale analysis of neuron and ion channel models and describe a novel tetrahedral structure formed by cell model clusters in the space of model properties and features. This analysis provides further information about model similarity to enrich database search

Filtering features for a composite event definition language

This research has enhanced a distributed, rule-based application integration environment with a composite event definition language (CEDL) and detection system. CEDL builds on existing composite event operators and selection modes, adding features to support the filtering of primitive and composite events. The filtering features include basic parameter filtering on primitive and composite events, aggregate and quantifier filters on cumulative event parameters, and time filters for defining the lifetime of the composite event detection process. This paper presents examples of CEDL, illustrating the expression of application-oriented events through the aggregation and correlation of distributed events. 1

Guideline Adherence of Monitoring Antipsychotic Use for Nonpsychotic Indications in Children and Adolescents A Patient Record Review:A Patient Record Review

Contains fulltext : 231603.pdf (Publisher’s version ) (Open Access

An investigation of trachoma vaccine regimens by the chlamydia vaccine CTH522 administered with cationic liposomes in healthy adults (CHLM-02): a phase 1, double-blind trial

Background There is no vaccine against the major global pathogen Chlamydia trachomatis; its different serovars cause trachoma in the eye or chlamydia in the genital tract. We did a clinical trial administering CTH522, a recombinant version of the C trachomatis major outer membrane molecule, in different dose concentrations with and without adjuvant, to establish its safety and immunogenicity when administered intramuscularly, intradermally, and topically into the eye, in prime-boost regimens. Methods CHLM-02 was a phase 1, double-blind, randomised, placebo-controlled trial at the National Institute for Health Research Imperial Clinical Research Facility, London, UK. Participants were healthy men and non-pregnant women aged 18–45 years, without pre-existing C trachomatis genital infection. Participants were assigned into six groups by the electronic database in a pre-prepared randomisation list (A–F). Participants were randomly assigned (1:1:1:1:1) to each of the groups A–E (12 participants each) and 6 were randomly assigned to group F. Investigators were masked to treatment allocation. Groups A–E received investigational medicinal product and group F received placebo only. Two liposomal adjuvants were compared, CAF01 and CAF09b. The groups were intramuscular 85 μg CTH522-CAF01, or placebo on day 0 and two boosters or placebo at day 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (A); intramuscular 85 μg CTH522-CAF01, two boosters at day 28 and 112 with additional topical ocular administration of CTH522, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (B); intramuscular 85 μg CTH522-CAF01, two boosters at day 28 and 112 with additional intradermal administration of CTH522, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (C); intramuscular 15 μg CTH522-CAF01, two boosters at day 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (D); intramuscular 85 μg CTH522-CAF09b, two boosters at day 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (E); intramuscular placebo (F). The primary outcome was safety; the secondary outcome (humoral immunogenicity) was the percentage of trial participants achieving anti-CTH522 IgG seroconversion, defined as four-fold and ten-fold increase over baseline concentrations. Analyses were done as intention to treat and as per protocol. The trial is registered with ClinicalTrials.gov, NCT03926728, and is complete. Findings Between Feb 17, 2020 and Feb 22, 2022, of 154 participants screened, 65 were randomly assigned, and 60 completed the trial (34 [52%] of 65 women, 46 [71%] of 65 White, mean age 26·8 years). No serious adverse events occurred but one participant in group A2 discontinued dosing after having self-limiting adverse events after both placebo and investigational medicinal product doses. Study procedures were otherwise well tolerated; the majority of adverse events were mild to moderate, with only seven (1%) of 865 reported as grade 3 (severe). There was 100% four-fold seroconversion rate by day 42 in the active groups (A–E) and no seroconversion in the placebo group. Serum IgG anti-CTH522 titres were higher after 85 μg CTH522-CAF01 than 15 μg, although not significantly (intention-to-treat median IgG titre ratio groups A–C:D=5·6; p=0·062), with no difference after three injections of 85 μg CTH522-CAF01 compared with CTH522-CAF09b (group E). Intradermal CTH522 (group C) induced high titres of serum IgG anti-CTH522 neutralising antibodies against serovars B (trachoma) and D (urogenital). Topical ocular CTH522 (group B) at day 28 and 112 induced higher total ocular IgA compared with baseline (p<0·001). Participants in all active vaccine groups, particularly groups B and E, developed cell mediated immune responses against CTH522. Interpretation CTH522, adjuvanted with CAF01 or CAF09b, is safe and immunogenic, with 85 μg CTH522-CAF01 inducing robust serum IgG binding titres. Intradermal vaccination conferred systemic IgG neutralisation breadth, and topical ocular administration increased ocular IgA formation. These findings indicate CTH522 vaccine regimens against ocular trachoma and urogenital chlamydia for testing in phase 2, clinical trials. Funding The EU Horizon Program TRACVAC

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics