A Bayesian learning approach to inconsistency identification in model-based systems engineering

Designing and developing complex engineering systems is a collaborative effort. In Model-Based Systems Engineering (MBSE), this collaboration is supported through the use of formal, computer-interpretable models, allowing stakeholders to address concerns using well-defined modeling languages. However, because concerns cannot be separated completely, implicit relationships and dependencies among the various models describing a system are unavoidable. Given that models are typically co-evolved and only weakly integrated, inconsistencies in the agglomeration of the information and knowledge encoded in the various models are frequently observed. The challenge is to identify such inconsistencies in an automated fashion. In this research, a probabilistic (Bayesian) approach to abductive reasoning about the existence of specific types of inconsistencies and, in the process, semantic overlaps (relationships and dependencies) in sets of heterogeneous models is presented. A prior belief about the manifestation of a particular type of inconsistency is updated with evidence, which is collected by extracting specific features from the models by means of pattern matching. Inference results are then utilized to improve future predictions by means of automated learning. The effectiveness and efficiency of the approach is evaluated through a theoretical complexity analysis of the underlying algorithms, and through application to a case study. Insights gained from the experiments conducted, as well as the results from a comparison to the state-of-the-art have demonstrated that the proposed method is a significant improvement over the status quo of inconsistency identification in MBSE.Ph.D

Tau, prions and Aβ: the triad of neurodegeneration

This article highlights the features that connect prion diseases with other cerebral amyloidoses and how these relate to neurodegeneration, with focus on tau phosphorylation. It also discusses similarities between prion disease and Alzheimer’s disease: mechanisms of amyloid formation, neurotoxicity, pathways involved in triggering tau phosphorylation, links to cell cycle pathways and neuronal apoptosis. We review previous evidence of prion diseases triggering hyperphosphorylation of tau, and complement these findings with cases from our collection of genetic, sporadic and transmitted forms of prion diseases. This includes the novel finding that tau phosphorylation consistently occurs in sporadic CJD, in the absence of amyloid plaques

Autonomía, Seguridad y Equidad de Usuarios Vulnerables: El caso de los adultos mayores y niños del AAHH. San Pedro del Agustino

TesisLa seguridad vial es un concepto clave de la movilidad sostenible; por ende, esta debe garantizar la protección de los usuarios más vulnerables como los peatones o ciclistas (Directorio General del Tráfico de España, 2011). En este sentido, a pesar de la existencia de números estudios sobre vulnerabilidad, un número reducido de estos analizan dicho concepto desde una perspectiva de movilidad (Rey & Cardozo, 2016). Ante ello, el presente trabajo de investigación propone un estudio sobre la autonomía y la vulnerabilidad de usuarios que habitan en lugares de pobreza e inseguridad; ello desde una perspectiva de movilidad sostenible. El tema de investigación nace de la observación del comportamiento en niños y ancianos del AAHH San Pedro, ubicado en el Agustino, el cual muestra características particulares, entre ellas, la autonomía de su desplazamiento pese a las circunstancias difíciles de su entorno. En consecuencia, se considera importante ahondar en estos nuevos conceptos para contribuir al desarrollo de la movilidad sostenible, así como para impulsar el cambio de paradigmas respecto al diseño tradicional del espacio público. Del mismo modo, se busca reflexionar sobre la importancia de tomar en cuenta a los usuarios vulnerables en la planificación de la ciudad. El método de investigación es de tipo mixto, es decir, comprende tanto un análisis cuantitativo como cualitativo. Para el cumplimiento de los objetivos, se elabora el estado del arte a través de la lectura y revisión de textos académicos y otras fuentes bibliográficas. En la parte cualitativa, se realiza un trabajo de campo que comprende la aplicación de encuestas, focus group, observación y entrevistas a 50 personas, entre niños y adultos mayores. En la parte cuantitativa, se realizan medidas geométricas del lugar así como la estimación aproximada de la velocidad con la que se desplazan ambos usuarios. Los resultados del estudio muestran que tanto adultos mayores como niños encuestados poseen un alto grado de autonomía (75% y 52%, respectivamente); además, ambos usuarios prefieren la caminata (67% de adultos mayores y 62% de niños) como modo de transporte, pese a las circunstancias adversas que impiden que esta se pueda dar de manera segura. Respecto a su desplazamiento, la velocidad promedio de los niños es de 1.26 m/s y el de los adultos mayores de 0.66 m/s. Asimismo, la inspección de seguridad vial evidencia el deficiente diseño del espacio urbano, la poca señalización y la deteriorada infraestructura, lo cual incrementa el riesgo de que ocurran accidentes de tránsito

Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial

Background: Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial. Methods: NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy. Findings: Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22–1·36), and the risk was similar for those without known PFO (1·06; 0·84–1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51–8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69–4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24–0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity. Interpretation: Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted. Funding: Bayer and Janssen