Increased neutrophil-lymphocyte ratio is a poor prognostic factor in patients with primary operable and inoperable pancreatic cancer

Background: The neutrophil-lymphocyte ratio (NLR) has been proposed as an indicator of systemic inflammatory response. Previous findings from small-scale studies revealed conflicting results about its independent prognostic significance with regard to different clinical end points in pancreatic cancer (PC) patients. Therefore, the aim of our study was the external validation of the prognostic significance of NLR in a large cohort of PC patients. Methods: Data from 371 consecutive PC patients, treated between 2004 and 2010 at a single centre, were evaluated retrospectively. The whole cohort was stratified into two groups according to the treatment modality. Group 1 comprised 261 patients with inoperable PC at diagnosis and group 2 comprised 110 patients with surgically resected PC. Cancer-specific survival (CSS) was assessed using the Kaplan–Meier method. To evaluate the independent prognostic significance of the NLR, the modified Glasgow prognostic score (mGPS) and the platelet-lymphocyte ratio univariate and multivariate Cox regression models were applied. Results: Multivariate analysis identified increased NLR as an independent prognostic factor for inoperable PC patients (hazard ratio (HR)=2.53, confidence interval (CI)=1.64–3.91, P<0.001) and surgically resected PC patients (HR=1.61, CI=1.02–2.53, P=0.039). In inoperable PC patients, the mGPS was associated with poor CSS only in univariate analysis (HR=1.44, CI=1.04–1.98). Conclusion: Risk prediction for cancer-related end points using NLR does add independent prognostic information to other well-established prognostic factors in patients with PC, regardless of the undergoing therapeutic modality. Thus, the NLR should be considered for future individual risk assessment in patients with PC

Cancer stem cell metabolism

Cancer is now viewed as a stem cell disease. There is still no consensus on the metabolic characteristics of cancer stem cells, with several studies indicating that they are mainly glycolytic and others pointing instead to mitochondrial metabolism as their principal source of energy. Cancer stem cells also seem to adapt their metabolism to microenvironmental changes by conveniently shifting energy production from one pathway to another, or by acquiring intermediate metabolic phenotypes. Determining the role of cancer stem cell metabolism in carcinogenesis has become a major focus in cancer research, and substantial efforts are conducted towards discovering clinical targets

A UML profile for developing airworthiness-compliant (RTCA DO-178B), safety-critical software

Many safety-related, certification standards exist for developing safety-critical systems. System safety assessments are common practice and system certification according to a standard requires submitting relevant software safety information to appropriate authorities. The airworthiness standard, RTCA DO-178B, is the de-facto standard for certifying aerospace systems containing software. This research introduces an approach to improve communication and collaboration among safety engineers and software engineers by proposing a Unified Modeling Language (UML) profile that allows software engineers to model safety-related concepts and properties in UML, the de-facto software modeling language. Key safety-related concepts are extracted from RTCA DO-178B, and then a UML profile is defined to enable their precise modeling. We show that the profile improves the line of communication between safety engineers and software engineers, for instance by allowing the automated generation of certification-related information from UML models. This is illustrated through a case study on developing an aircraft's navigation controller subsystem

Modeling safety and airworthiness (RTCA DO-178B) information: Conceptual model and UML profile

Several safety-related standards exist for developing and certifying safety-critical systems. System safety assessments are common practice and system certification according to a standard requires submitting relevant system safety information to appropriate authorities. The RTCA DO-178B standard is a software quality assurance, safety-related standard for the development of software aspects of aerospace systems. This research introduces an approach to improve communication and collaboration among safety engineers, software engineers, and certification authorities in the context of RTCA DO-178B. This is achieved by utilizing a Unified Modeling Language (UML) profile that allows software engineers to model safety-related concepts and properties in UML, the de facto software modeling standard. A conceptual meta-model is defined based on RTCA DO-178B, and then a corresponding UML profile, which we call SafeUML, is designed to enable its precise modeling. We show how SafeUML improves communication by, for example, allowing monitoring implementation of safety requirements during the development process, and supporting system certification per RTCA DO-178B. This is enabled through automatic generation of safety and certification-related information from UML models. We validate this approach through a case study on developing an aircraft's navigation controller subsystem

Extracting models from ISO 26262 for reusable safety assurance

As more and more complex software is deployed in safety-critical embedded systems, the challenge of assessing the safety of those systems according to the relevant standards is becoming greater. Due to the extensive manual work required, validating compliance of these systems with safety standards is an expensive and time-consuming activity; furthermore, as products evolve, re-assessment may become necessary. Therefore, obtaining reusable assurance data for safety assessment or re-assessment is very desirable. In this paper, we propose a model-based approach for assuring compliance with safety standards to facilitate reuse in the assessment, qualification and certification processes, using the automotive safety standard ISO 26262 as a specific example. Three different modeling techniques are described: A structure model is introduced to describe the overall structure of the standard; a rule-based technique is used for extracting the conceptual model from it; and a mapping to the software and systems process engineering metamodel provides a description of its processes. Finally, validation in the context of a concrete use case in the FP7 project OPENCOSS shows that the resulting models of our approach resemble the industrial models, but that they, inevitably, require the fine-tuning of domain experts

INCREMENT: A Mixed MDE-IR Approach for Regulatory Requirements Modeling and Analysis

International audience[Context and motivation] Regulatory requirements for Nuclear instrumentation and control (I&C) systems are first class requirements. They are written by national safety entities and are completed through a large documentation set of national recommendation guidesandnational/internationalstandards. [Question/Problem] I&C systems important to safety must comply to all of these requirements. The global knowledge of this domain is scattered through these different documents and not formalized. Its organization and traceability relationships within this domain is mainly implicit. As a consequence, such long lasting nuclear I&C projects set important challenges in terms of tacit expertise capitalization and domain analysis. [Principal ideas/results] To tackle this domain formalization issue, we propose a dual Model-driven Engineering (MDE) and Information Retrieval (IR) approach to address the nuclear regulatory requirements domain definition, and assisted traceability based on the acquired requirements model. [Contributions] In this paper, we present the Connexion metamodel that pro- vides a canvas for the definition and capitalization of the nuclear regu- latory requirements domain. We also present an hybrid MDE/IR-based approach, named INCREMENT, for acquiring, modeling and analyzing these regulatory requirements. This approach is supported by a tool that is developed in the context of the CONNEXION project, which gathers French major nuclear I&C industrial actors