Abstract
Exome and whole-genome sequencing are becoming increasingly routine approaches in Mendelian disease diagnosis. Despite their success, the current diagnostic rate for genomic analyses across a variety of rare diseases is approximately 25 to 50%. We explore the utility of transcriptome sequencing [RNA sequencing (RNA-seq)] as a complementary diagnostic tool in a cohort of 50 patients with genetically undiagnosed rare muscle disorders. We describe an integrated approach to analyze patient muscle RNA-seq, leveraging an analysis framework focused on the detection of transcript-level changes that are unique to the patient compared to more than 180 control skeletal muscle samples. We demonstrate the power of RNA-seq to validate candidate splice-disrupting mutations and to identify splice-altering variants in both exonic and deep intronic regions, yielding an overall diagnosis rate of 35%. We also report the discovery of a highly recurrent de novo intronic mutation in COL6A1 that results in a dominantly acting splice-gain event, disrupting the critical glycine repeat motif of the triple helical domain. We identify this pathogenic variant in a total of 27 genetically unsolved patients in an external collagen VI-like dystrophy cohort, thus explaining approximately 25% of patients clinically suggestive of having collagen VI dystrophy in whom prior genetic analysis is negative. Overall, this study represents a large systematic application of transcriptome sequencing to rare disease diagnosis and highlights its utility for the detection and interpretation of variants missed by current standard diagnostic approaches. 2017 © The Authors.

Abstract
Introduction: The establishment of prognostic models for Crohn's disease [CD] is highly desirable, as they have the potential to guide physicians in the decision-making process concerning therapeutic choices, thus improving patients' health and quality of life. Our aim was to derive models for disabling CD and reoperation based solely on clinical/demographic data. Methods: A multicentric and retrospectively enrolled cohort of CD patients, subject to early surgery or immunosuppression, was analysed in order to build Bayesian network models and risk matrices. The final results were validated internally and with a multicentric and prospectively enrolled cohort. Results: The derivation cohort included a total of 489 CD patients [64% with disabling disease and 18% who needed reoperation], while the validation cohort included 129 CD patients with similar outcome proportions. The Bayesian models achieved an area under the curve of 78% for disabling disease and 86% for reoperation. Age at diagnosis, perianal disease, disease aggressiveness and early therapeutic decisions were found to be significant factors, and were used to construct user-friendly matrices depicting the probability of each outcome in patients with various combinations of these factors. The matrices exhibit good performance for the most important criteria: disabling disease positive post-test odds = 8.00 [2.72-23.44] and reoperation negative post-test odds = 0.02 [0.00-0.11]. Conclusions: Clinical and demographical risk factors for disabling CD and reoperation were determined and their impact was quantified by means of risk matrices, which are applicable as bedside clinical tools that can help physicians during therapeutic decisions in early disease management.

Abstract

Abstract
Resource efficiency assessment methods, along with eco-efficiency assessment methods are needed for various industrial sectors to support sustainable development, decision-making and evaluate efficiency performance. The combination of eco-efficiency with efficiency assessment allows to identify major inefficiencies and provides means to foster sustainability, through the efficient and effective material and energy use. Despite the available information for decision making, this proves to be a difficult task in the manufacturing industry, therefore, there is a real need to develop and use optimization techniques to enhance resource efficiency. In this context, and due to the lack of simple and integrated tools to assess and optimize resource efficiency, crossing the different environmental and economic aspects, arises the need to develop optimisations models, enabling support and optimize sustainable decision making process and identification of potential improvements. The optimisation method should provide robust knowledge to support decisionmaking, allow comparability of the results and consider a cost-saving approach to help set priorities. Moreover, the optimisation techniques should centre the process through design/configuration of the production system, without considering time, in order not to limit the physical agents.

Abstract
Hybrid simulation is nowadays a valid alternative for studying complex manufacturing environments. Some challenges exist in this context, as the ambiguous use of terms and definitions in the literature; and the demanding skills required for developing hybrid models. A structured literature review provides an overview of the use of hybrid simulation in manufacturing business performance and its most important advantages and drawbacks. A classification scheme for the 51 analysed papers is presented, including interfaced, sequential, enrichment, and integrated taxonomies. (C) 2017 The Authors. Published by Elsevier B.V.

Abstract
An emerging trend in industry 4.0 is to use wireless communication infrastructure and mesh networks in applications requiring high reliability and safety. Although not a typical industrial production process, railway vehicular networks are also an industrial application which come with stringent reliability and safety requirements. Current research is focusing on using vehicular networks as an enabling technology to actively control the separation between two consecutive vehicles, enforcing a safe distance which is nevertheless much shorter than currently used to maintain vehicle separation. In this respect, we analyze a hopping strategy for Time-Slotted Channel-Hopping (TSCH), which was introduced in the IEEE 802.15.4e amendment with a view of improving the reliability of IEEE 802.15.4 networks. We define a probability framework to estimate the chance of successful hopping assuming two previously merged vehicles, and we design a zero-sum game and propose a payoff function to always place communicating nodes in a Nash equilibrium by choosing whether to hop or not, and therefore maximizing the communication throughput by mitigating jamming signals.