8 research outputs found
Implementation of a production Ada project: The GRODY study
The use of the Ada language and design methodologies that encourage full use of its capabilities have a strong impact on all phases of the software development project life cycle. At the National Aeronautics and Space Administration/Goddard Space Flight Center (NASA/GSFC), the Software Engineering Laboratory (SEL) conducted an experiment in parallel development of two flight dynamics systems in FORTRAN and Ada. The differences observed during the implementation, unit testing, and integration phases of the two projects are described and the lessons learned during the implementation phase of the Ada development are outlined. Included are recommendations for future Ada development projects
Lessons learned in the transition to Ada from FORTRAN at NASA/Goddard
Two dynamics satellite simulators are developed from the same requirements, one in Ada and the other in FORTRAN. The purpose of the research was to find out how well the prescriptive Ada development model worked to develop the Ada simulator. The FORTRAN simulator development, as well as past FORTRAN developments, provided a baseline for comparison. Since this was the first simulator developed, the prescriptive Ada development model had many similarities to the usual FORTRAN development model. However, it was modified to include longer design and shorter testing phases, which is generally expected with Ada developments. One result was that the percentage of time the Ada project spent in the various development activities was very similar to the percentage of time spent in these activities when doing a FORTRAN project. Another finding was the difficulty the Ada team had with unit testing as well as with integration. It was realized that adding additional steps to the design phase, such as an abstract data type analysis, and certain guidelines to the implementation phase, such as to use primarily library units and nest sparingly, would have made development easier. These are among the recommendations made to be incorporated in a new Ada development model next time
Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function
Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes
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Incidence and Risk Factors of Early Onset Neonatal AKI
Background and objectives Neonatal AKI is associated with poor short-and long-term outcomes. The objective of this study was to describe the risk factors and outcomes of neonatal AKI in the first postnatal week.
Design, setting, participants, & measurements The international retrospective observational cohort study, Assessment of Worldwide AKI Epidemiology in Neonates (AWAKEN), included neonates admitted to a neonatal intensive care unit who received at least 48 hours of intravenous fluids. Early AKI was defined by an increase in serumcreatinine. 0.3mg/dl or urine output, 1ml/kg per hour on postnatal days 2-7, the neonatalmodification of KidneyDisease: ImprovingGlobalOutcomes criteria. We assessed risk factors forAKI and associations ofAKI with death and duration of hospitalization.
ResultsTwenty-onepercent (449of 2110) experiencedearlyAKI. EarlyAKIwas associatedwithhigher riskof death (adjusted odds ratio, 2.8; 95% confidence interval, 1.7 to 4.7) and longer duration of hospitalization (parameter estimate: 7.3 days 95% confidence interval, 4.7 to 10.0), adjusting for neonatal and maternal factors along with medication exposures. Factors associated with a higher risk of AKI included: outborn delivery; resuscitation with epinephrine; admission diagnosis of hyperbilirubinemia, inborn errors of metabolism, or surgical need; frequent kidney function surveillance; and admission to a children's hospital. Those factors that were associated with a lower risk includedmultiplegestations, cesarean section, andexposuresto antimicrobials, methylxanthines, diuretics, and vasopressors. Risk factors varied by gestational age strata.
Conclusions AKI in the first postnatal week is common and associated with death and longer duration of hospitalization. The AWAKEN study demonstrates a number of specific risk factors that should serve as "red flags" for clinicians at the initiation of the neonatal intensive care unit course