An experimental evaluation of the understanding of safety compliance needs with models

Proceedings of: 36th International Conference on Conceptual Modeling, ER 2017, Valencia, Spain, November 6–9, 2017Context: Most safety-critical systems have to fulfil compliance needs specified in safety standards. These needs can be difficult to understand from the text of the standards, and the use of conceptual models has been proposed as a solution. Goal: We aim to evaluate the understanding of safety compliance needs with models. Method: We have conducted an experiment to study the effectiveness, efficiency, and perceived benefits in understanding these needs, with text of safety standards and with UML object diagrams. Results: Sixteen Bachelor students participated in the experiment. Their average effectiveness in understanding compliance needs and their average efficiency were higher with models (17% and 15%, respectively). However, the difference is not statistically significant. The students found benefits in using models, but on average they are undecided about their ease of understanding. Conclusions: Although the results are not conclusive enough, they suggest that the use of models could improve the understanding of safety compliance needs.The research leading to this paper has received funding from the AMASS project (H2020-ECSEL grant agreement no 692474; Spain’s MINECO ref. PCIN-2015-262) and the AMoDDI project (Ref. 11130583). We also thank the subjects that participated in the experiment

Assessment of the Quality of Safety Cases: A Research Preview

Proceedings of the 25th International Working Conference, REFSQ 2019, Essen, Germany, March 18–21, 2019.[Context and motivation] Safety-critical systems in application domains such as aerospace, automotive, healthcare, and railway are subject to assurance processes to provide confidence that the systems do not pose undue risks to people, property, or the environment. The development of safety cases is usually part of these processes to justify that a system satisfies its safety requirements and thus is dependable. [Question/problem] Although safety cases have been used in industry for over two decades, their management still requires improvement. Important weaknesses have been identified and means to assess the quality of safety cases are limited. [Principal ideas/results] This paper presents a research preview on the assessment of the quality of safety cases. We explain how the area should develop and present our preliminary work towards enabling the assessment with Verification Studio, an industrial tool for system artefact quality analysis. [Contribution] The insights provided allow researchers and practitioners to gain an understanding of why safety case quality requires further investigation, what aspects must be considered, and how quality assessment could be performed in practice.The research leading to this paper has received funding from the AMASS project (H2020-ECSEL ID 692474; Spain’s MINECO ref. PCIN-2015-262). We also thank REFSQ reviewers for their valuable comments to improve the paper

Effects of dietary beef tallow on performance, rumen fermentation, carcass traits and meat quality of growing lambs

Growing lambs were evaluated for the effect of increasing dietary levels of beef tallow (BT) on performance, rumen fermentation, and carcass and meat characteristics. Twenty-one 5-month-old male Rambouillet lambs were assigned randomly to one of three diets with 0, 20, and 40 g BT/kg dry matter (DM) and similar energy and protein contents. Lambs were adapted to the diets for 15 days, followed by a 45-day evaluation trial. Data were analysed using a mixed model. Growth, feed intake and ruminal fermentation were not affected by the dietary level of BT. Daily metabolizable energy intake (MEI), carcass yield and degree of fatness, increased linearly as the BT level increased. Carcass classification and muscle conformation were not affected by BT. Most meat characteristics (texture, pH, myoglobin, protein content, colour, cathepsins, and chemical composition) five and eight days post-mortem were not affected, except for fat content in meat, which increased linearly as diet BT level increased. Fatty acid (FA) profiles of the meat from lambs fed the three diets were similar. In conclusion, addition of BT at 20 and 40 g/kg DM to diets for growing lambs allowed reduced grain usage and increased forage levels (from 0 to 270 g/kg DM), increasing energy intake, carcass yield and fatness, and intramuscular fat without causing harmful effects on growth, feed intake or ruminal fermentation characteristics. Keywords: dietary fat, fatty acids, meat colour, shee

Oxidized low-density lipoprotein receptor in lymphocytes prevents atherosclerosis and predicts subclinical disease

Background: Although the role of Th17 and regulatory T cells in the progression of atherosclerosis has been highlighted in recent years, their molecular mediators remain elusive. We aimed to evaluate the association between the CD69 receptor, a regulator of Th17/regulatory T cell immunity, and atherosclerosis development in animal models and in patients with subclinical disease. Methods: Low-density lipoprotein receptor-deficient chimeric mice expressing or not expressing CD69 on either myeloid or lymphoid cells were subjected to a high fat diet. In vitro functional assays with human T cells were performed to decipher the mechanism of the observed phenotypes. Expression of CD69 and NR4A nuclear receptors was evaluated by reverse transcription-polymerase chain reaction in 305 male participants of the PESA study (Progression of Early Subclinical Atherosclerosis) with extensive (n=128) or focal (n=55) subclinical atherosclerosis and without disease (n=122). Results: After a high fat diet, mice lacking CD69 on lymphoid cells developed large atheroma plaque along with an increased Th17/regulatory T cell ratio in blood. Oxidized low-density lipoprotein was shown to bind specifically and functionally to CD69 on human T lymphocytes, inhibiting the development of Th17 cells through the activation of NR4A nuclear receptors. Participants of the PESA study with evidence of subclinical atherosclerosis displayed a significant CD69 and NR4A1 mRNA downregulation in peripheral blood leukocytes compared with participants without disease. The expression of CD69 remained associated with the risk of subclinical atherosclerosis in an adjusted multivariable logistic regression model (odds ratio, 0.62; 95% CI, 0.40-0.94; P=0.006) after adjustment for traditional risk factors, the expression of NR4A1, the level of oxidized low-density lipoprotein, and the counts of different leucocyte subsets. Conclusions: CD69 depletion from the lymphoid compartment promotes a Th17/regulatory T cell imbalance and exacerbates the development of atherosclerosis. CD69 binding to oxidized low-density lipoprotein on T cells induces the expression of anti-inflammatory transcription factors. Data from a cohort of the PESA study with subclinical atherosclerosis indicate that CD69 expression in PBLs inversely correlates with the presence of disease. The expression of CD69 remained an independent predictor of subclinical atherosclerosis after adjustment for traditional risk factors.Funding was provided by the Spanish Ministry of Economy and Competitiveness: Plan Nacional de Salud SAF2017-82886-R to Dr Sánchez-Madrid, SAF2015-64767-R to Dr Martínez-González; Instituto de Salud Carlos III (AES 2016): PI16/01956 to Dr Martin, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares; European Research Council, ERC- 2011-AdG294340-GENTRIS to Dr Sánchez-Madrid; Proyecto Integrado de Excelencia PIE13/041 and Fundació La Marató TV3 (20152330 31); and Comunidad Autónoma de Madrid CAM (S2017/BMD-3671) to Drs Martin and Sánchez-Madrid. Dr Tsilingiri is cofunded by the European Union Marie Curie Program. M. Relaño is supported by a Contratos Predoctorales Severo Ochoa para la formación de doctores (BES-2015–072625) from the Spanish Ministry of Economy and Competitiveness. This research has been cofinanced by Fondo Europeo de Desarrollo Regional. Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain, is supported by the Ministerio de Ciencia, Innovación y Universidades, and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505). The PESA study is cofunded equally by the Pro CNIC Foundation and Banco Santander, Madrid, Spai

Naming the pain in requirements engineering : Contemporary problems, causes, and effects in practice

Requirements Engineering (RE) has received much attention in research and practice due to its importance to software project success. Its interdisciplinary nature, the dependency to the customer, and its inherent uncertainty still render the discipline difficult to investigate. This results in a lack of empirical data. These are necessary, however, to demonstrate which practically relevant RE problems exist and to what extent they matter. Motivated by this situation, we initiated the Naming the Pain in Requirements Engineering (NaPiRE) initiative which constitutes a globally distributed, bi-yearly replicated family of surveys on the status quo and problems in practical RE. In this article, we report on the qualitative analysis of data obtained from 228 companies working in 10 countries in various domains and we reveal which contemporary problems practitioners encounter. To this end, we analyse 21 problems derived from the literature with respect to their relevance and criticality in dependency to their context, and we complement this picture with a cause-effect analysis showing the causes and effects surrounding the most critical problems. Our results give us a better understanding of which problems exist and how they manifest themselves in practical environments. Thus, we provide a first step to ground contributions to RE on empirical observations which, until now, were dominated by conventional wisdom only.Peer reviewe

Neurocognitive outcome and mental health in children with tyrosinemia type 1 and phenylketonuria: A comparison between two genetic disorders affecting the same metabolic pathway

Tyrosinemia type 1 (TT1) and phenylketonuria (PKU) are both inborn errors of phenylalanine–tyrosine metabolism. Neurocognitive and behavioral outcomes have always featured in PKU research but received less attention in TT1 research. This study aimed to investigate and compare neurocognitive, behavioral, and social outcomes of treated TT1 and PKU patients. We included 33 TT1 patients (mean age 11.24 years; 16 male), 31 PKU patients (mean age 10.84; 14 male), and 58 age- and gender-matched healthy controls (mean age 10.82 years; 29 male). IQ (Wechsler-subtests), executive functioning (the Behavioral Rating Inventory of Executive Functioning), mental health (the Achenbach-scales), and social functioning (the Social Skills Rating System) were assessed. Results of TT1 patients, PKU patients, and healthy controls were compared using Kruskal–Wallis tests with post-hoc Mann–Whitney U tests. TT1 patients showed a lower IQ and poorer executive functioning, mental health, and social functioning compared to healthy controls and PKU patients. PKU patients did not differ from healthy controls regarding these outcome measures. Relatively poor outcomes for TT1 patients were particularly evident for verbal IQ, BRIEF dimensions “working memory”, “plan and organize” and “monitor”, ASEBA dimensions “social problems” and “attention problems”, and for the SSRS “assertiveness” scale (all p values <0.001). To conclude, TT1 patients showed cognitive impairments on all domains studied, and appeared to be significantly more affected than PKU patients. More attention should be paid to investigating and monitoring neurocognitive outcome in TT1 and research should focus on explaining the underlying pathophysiological mechanism

Spatial evolution of an AMD stream in the Iberian Pyrite Belt: process characterization and control factors on the hydrochemistry

This paper presents hydrochemical data of an AMD stream in the Iberian Pyrite Belt, obtained from its source, in the Poderosa Mine Portal, till its confluence at the Odiel River. The main objective is to establish potential interdependent relations between sulfate and metals’ loads and the following physical-chemical variables: pH, electric conductivity (EC), redox potential (EH), and dissolved oxygen (O2). All the parameters show a global increasing tendency since the tunnel’s exit to the confluence at Odiel River. The TDS and EC are two relevant exceptions. They behave similarly, showing a decreasing trend and a strong inflection that describes a minimum immediately after the discharging point. The spatial analysis combined with statistical tools put in evidence the typical AMD processes and the respective physical-chemical implications. Inputs with distinctive hydrochemical signatures impose relevant modifications in the Poderosa creek waters. This indicates low hydrochemical inertia and high vulnerability to external stimulus.Financial support for this research was provided by DGCICYT National Plan, project CGL2010-21268-C02-01 and the Andalusian Autonomous Government Excellence Projects, Project RNM-6570

Age-Specific Differences in Oncogenic Pathway Deregulation Seen in Human Breast Tumors

Purpose. To define the biology driving the aggressive nature of breast cancer arising in young women. Experimental Design. Among 784 patients with early stage breast cancer, using prospectively-defined, age-specific cohorts (young ≤45 years; older ≥65 years), 411 eligible patients (n = 200≤545 years; n = 211≥65 years) with clinically-annotated Affymetrix microarray data were identified. GSEA, signatures of oncogenic pathway deregulation and predictors of chemotherapy sensitivity were evaluated within the two age-defined cohorts. Results. In comparing deregulation of oncogenic pathways between age groups, a higher probability of P13K (p = 0.006) and Myc (p = 0.03) pathway deregulation was observed in breast tumors arising in younger women. When evaluating unique patterns of pathway deregulation, a low probability of Src and E2F deregulation in tumors of younger women, concurrent with a higher probability of P13K, Myc, and β-catenin, conferred a worse prognosis (HR = 4.15). In contrast, a higher probability of Src and E2F pathway activation in tumors of older women, with concurrent low probability of P13K, Myc and β-catenin deregulation, was associated with poorer outcome (HR = 2.7). In multivariate analyses, genomic clusters of pathway deregulation illustrate prognostic value. Conclusion. Results demonstrate that breast cancer arising in young women represents a distinct biologic entity characterized by unique patterns of deregulated signaling pathways that are prognostic, independent of currently available clinico-pathologic variables. These results should enable refinement of targeted treatment strategies in this clinically challenging situation. Copyright

Neurocognitive outcome and mental health in children with tyrosinemia type 1 and phenylketonuria:A comparison between two genetic disorders affecting the same metabolic pathway

Tyrosinemia type 1 (TT1) and phenylketonuria (PKU) are both inborn errors of phenylalanine-tyrosine metabolism. Neurocognitive and behavioral outcomes have always featured in PKU research but received less attention in TT1 research. This study aimed to investigate and compare neurocognitive, behavioral, and social outcomes of treated TT1 and PKU patients. We included 33 TT1 patients (mean age 11.24 years; 16 male), 31 PKU patients (mean age 10.84; 14 male), and 58 age- and gender-matched healthy controls (mean age 10.82 years; 29 male). IQ (Wechsler-subtests), executive functioning (the Behavioral Rating Inventory of Executive Functioning), mental health (the Achenbach-scales), and social functioning (the Social Skills Rating System) were assessed. Results of TT1 patients, PKU patients, and healthy controls were compared using Kruskal-Wallis tests with post-hoc Mann-Whitney U tests. TT1 patients showed a lower IQ and poorer executive functioning, mental health, and social functioning compared to healthy controls and PKU patients. PKU patients did not differ from healthy controls regarding these outcome measures. Relatively poor outcomes for TT1 patients were particularly evident for verbal IQ, BRIEF dimensions "working memory", "plan and organize" and "monitor", ASEBA dimensions "social problems" and "attention problems", and for the SSRS "assertiveness" scale (all p value