Logic-based schedulability analysis for compositional hard real-time embedded systems

This is the author's version of the work. It is posted here by permission of ACM for your personal use. Not for redistribution. The definitive version was published in SIGBED Review, VOL.12, ISS.1, http://doi.acm.org/10.1145/2752801.2752808Over the past decades several approaches for schedu- lability analysis have been proposed for both uniprocessor and multi-processor real-time systems. Although different techniques are employed, very little has been put forward in using formal specifications, with the consequent possibility for misinterpretations or ambiguities in the problem statement. Using a logic based approach to schedulability analysis in the design of hard real-time systems eases the synthesis of correct-by- construction procedures for both static and dynamic verification processes. In this paper we propose a novel approach to schedulability analysis based on a timed temporal logic with time durations. Our approach subsumes classical methods for uniprocessor scheduling analysis over compositional resource models by providing the developer with counter-examples, and by ruling out schedules that cause unsafe violations on the system. We also provide an example showing the effectiveness of our proposal.This work was partially supported by National Funds through FCT (Portuguese Foundation for Science and Technology) and by ERDF (European Regional Development Fund) through COMPETE (Operational Programme ’Thematic Fac- tors of Competitiveness’), within projects Ref. FCOMP-01- 0124-FEDER-022701 (CISTER), FCOMP-01-0124-FEDER- 015006 (VIPCORE) and FCOMP-01-0124-FEDER-020486 (AVIACC)

The Contribution of National Spontaneous Reporting Systems to Detect Signals of Torsadogenicity: Issues Emerging from the ARITMO Project

Introduction: Spontaneous reporting systems (SRSs) are pivotal for signal detection, especially for rare events with a high drug-attributable component, such as torsade de pointes (TdP). Use of different national SRSs is rarely attempted because of inherent difficulties, but should be considered on the assumption that rare events are diluted in international databases. Objective: The aim was to describe TdP-related events associated with antipsychotics, H1-antihistamines and anti-infectives in three national SRSs (in Italy, Germany and France) and highlight potential signals of torsadogenicity through a combined literature evaluation. Methods: A common search strategy was applied to extract TdP-related events: (1) TdP, (2) QT interval abnormalities, (3) ventricular fibrillation/tachycardia, and (4) sudden cardiac death. Signals of disproportionate reporting (SDRs) were calculated for TdP + QT interval abnormalities and defined by a lower limit of the 95 % confidence interval of the reporting odds ratio (ROR) >1. Among SDRs with at least three cases without concomitant pro-arrhythmic drugs, we defined potential new signal of torsadogenicity as drugs with no published evidence from (a) the crediblemeds® website (http://www.crediblemeds.com, as of November 1st, 2014); (b) studies on the FDA Adverse Event Reporting System (FAERS); and (c) safety trials or pharmaco-epidemiological studies (as of December 16th, 2014). Results: Overall, 3505 cases were retrieved (1372, 1468, and 801 for France, Germany and Italy, respectively). Antipsychotics were mainly recorded in Germany (792 cases), whereas antibiotics peaked at 515 and 491 (France and Italy, respectively). Forty-one drugs met criteria for SDRs in at least one single source, of which 31 were detected only from one single SRS: 18, ten and three (French, German and Italian SRS, respectively). By contrast, only five SDRs were detected in all national data sources (amisulpride, aripiprazole, haloperidol, olanzapine, risperidone). Overall, five potential new signals of torsadogenicity were identified: flupentixol, ganciclovir, levocetirizine, oxatomide and tiapride. Conclusions: We found differences across and within national SRSs in the reporting of drug-induced TdP, which finally resulted in five potential new signals of torsadogenicity. These findings warrant targeted pharmacovigilance studies to formally assess the existence of actual drug–event associations

Effect of starch-based biomaterials on the in vitro proliferation and viability of osteoblast-like cells

The cytotoxicity of starch-based polymers was investigated using different methodologies. Poly-L-lactic acid (PLLA) was used as a control for comparison purposes. Extracts of four different starch-based blends (corn starch and ethylene vinyl alcohol (SEVA-C), corn starch and cellulose acetate (SCA), corn starch and polycaprolactone (SPCL) and starch and poly-lactic acid (SPLA70) were prepared in culture medium and their toxicity was analysed. Osteoblast-like cells (SaOs-2) were incubated with the extracts and cell viability was assessed using the MTT test and a lactate dehydrogenase (LDH) assay. In addition DNA and total protein were quantified in order to evaluate cell proliferation. Cells were also cultured in direct contact with the polymers for 3 and 7 days and observed in light and scanning electron microscopy (SEM). LDH and DNA quantification revealed to be the most sensitive tests to assess respectively cell viability and cell proliferation after incubation with starch-based materials and PLLA. SCA was the starch blend with higher cytotoxicity index although similar to PLLA polymer. Cell adhesion tests confirmed the worst performance of the blend of starch with cellulose acetate but also showed that SPCL does not perform as well as it could be expected. All the other materials were shown to present a comparable behaviour in terms of cell adhesion showing slight differences in morphology that seem to disappear for longer culture times. The results of this study suggest that not only the extract of the materials but also their three-dimensional form has to be biologically tested in order to analyse material-associated parameters that are not possible to consider within the degradation extract. In this study, the majority of the starch-based biomaterials presented very promising results in terms of cytotoxicity, comparable to the currently used biodegradable PLLA which might lead the biocompatibility evaluation of those novel biomaterials to other studies.Fundação para a Ciência e a Tecnologia (FCT

Patterning gold nanoparticle using scanning electrochemical microscopy

Patterned arrays of gold nanoparticles (AuNPs) are prepared using scanning electrochemical microscopy by electrochemical reduction of a gold salt at a platinum ultramicroelectrode positioned on top of an unbiased gold surface, modified with a biphenyl dithiol self-assembled monolayer (SAM). The synthesized AuNPs are chemisorbed on the thiolated SAM, and by moving the microelectrode in a lateral direction across the surface while applying a reduction potential, particle-like lines are generate

Effect of Shot Peening on Oxidation and Precipitation in Inconel 718

In this study, the effect of the surface state on the behaviour of Inconel 718 alloy exposed to 640 ∘ C and 700 ∘ C environments for times varying between one and one hundred hours was investigated. In particular, the focus was set on the evolution of oxidation and precipitation phenomena during thermal exposure. Three surface states were considered: two generated through shot peening treatments featuring different coverage levels, while the third condition is a non-peened one. Shot peening treatments modify the surface condition and introduce higher residual stresses and microhardness values than in the non-treated condition. The morphology of the oxides appears to be different depending on the condition observed. Regarding the kinetics, over time the oxidation process follows a parabolic trend and appears to be influenced by the surface state; in particular, severe shot peening treatment is characterized by the highest intensity of the phenomenon. However, the order of magnitude of the weight gains measured suggests that the observed variations can be neglected, and that the positive effect of shot peening can be exploited without introducing oxidation problems. From the point of view of the microstructural evolution, an increase in the coarsening kinetics of γ ” phase was observed in the shot peened layer

Effect of shot peening on oxidation and precipitation in Inconel 718

Open Access funding provided by Politecnico di Milano within the CRUI-CARE Agreement

Mapping Strategies to Assess and Increase the Validity of Published Disproportionality Signals: A Meta-Research Study

Background and Aim: Disproportionality analysis is traditionally used in spontaneous reporting systems to generate working hypotheses about potential adverse drug reactions: the so-called disproportionality signals. We aim to map the methods used by researchers to assess and increase the validity of their published disproportionality signals. Methods: From a systematic literature search of published disproportionality analyses up until 1 January 2020, we randomly selected and analyzed 100 studies. We considered five domains: (1) rationale for the study, (2) design of disproportionality analyses, (3) case-by-case assessment, (4) use of complementary data sources, and (5) contextualization of the results within existing evidence. Results: Among the articles, multiple strategies were adopted to assess and enhance the results validity. The rationale, in 95 articles, was explicitly referred to the accrued evidence, mostly observational data (n = 46) and regulatory documents (n = 45). A statistical adjustment was performed in 34 studies, and specific strategies to correct for biases were implemented in 33 studies. A case-by-case assessment was complementarily performed in 35 studies, most often by investigating temporal plausibility (n = 26). Complementary data sources were used in 25 articles. In 78 articles, results were contextualized using accrued evidence from the literature and regulatory documents, the most important sources being observational (n = 45), other disproportionalities (n = 37), and case reports (n = 36). Conclusions: This meta-research study highlighted the heterogeneity in methods and strategies used by researchers to assess the validity of disproportionality signals. Mapping these strategies is a first step towards testing their utility in different scenarios and developing guidelines for designing future disproportionality analysis