Diagnostic implications of genetic copy number variation in epilepsy plus

Objective: Copy number variations (CNVs) represent a significant genetic risk for several neurodevelopmental disorders including epilepsy. As knowledge increases, reanalysis of existing data is essential. Reliable estimates of the contribution of CNVs to epilepsies from sizeable populations are not available. Methods: We assembled a cohort of 1255 patients with preexisting array comparative genomic hybridization or single nucleotide polymorphism array based CNV data. All patients had “epilepsy plus,” defined as epilepsy with comorbid features, including intellectual disability, psychiatric symptoms, and other neurological and nonneurological features. CNV classification was conducted using a systematic filtering workflow adapted to epilepsy. Results: Of 1097 patients remaining after genetic data quality control, 120 individuals (10.9%) carried at least one autosomal CNV classified as pathogenic; 19 individuals (1.7%) carried at least one autosomal CNV classified as possibly pathogenic. Eleven patients (1%) carried more than one (possibly) pathogenic CNV. We identified CNVs covering recently reported (HNRNPU) or emerging (RORB) epilepsy genes, and further delineated the phenotype associated with mutations of these genes. Additional novel epilepsy candidate genes emerge from our study. Comparing phenotypic features of pathogenic CNV carriers to those of noncarriers of pathogenic CNVs, we show that patients with nonneurological comorbidities, especially dysmorphism, were more likely to carry pathogenic CNVs (odds ratio = 4.09, confidence interval = 2.51-6.68; P = 2.34 × 10−9). Meta-analysis including data from published control groups showed that the presence or absence of epilepsy did not affect the detected frequency of CNVs. Significance: The use of a specifically adapted workflow enabled identification of pathogenic autosomal CNVs in 10.9% of patients with epilepsy plus, which rose to 12.7% when we also considered possibly pathogenic CNVs. Our data indicate that epilepsy with comorbid features should be considered an indication for patients to be selected for a diagnostic algorithm including CNV detection. Collaborative large-scale CNV reanalysis leads to novel declaration of pathogenicity in unexplained cases and can promote discovery of promising candidate epilepsy genes

Joint optimisation of operation and maintenance policies in an urban ropeway transport systems context

Purpose: The purpose of this paper is to propose a stochastic optimisation model for integrating service and maintenance policies in order to solve the queuing problem and the cost of maintenance activities for public transport services, with a particular focus on urban ropeway system. Design/methodology/approach: The authors adopt the following approaches: a discrete-event model that uses a set of interrelated queues for the formulation of the service problem using a cost-based expression; and a maintenance model consisting of preventive and corrective maintenance actions, which considers two different maintenance policies (periodic block-type and age-based). Findings: The work shows that neither periodic block-type maintenance nor an age-based maintenance is necessarily the best maintenance strategy over a long system lifecycle; the optimal strategy must consider both policies. Practical implications: The maintenance policies are then evaluated for their impact on the service and operation of the transport system. The authors conclude by applying the proposed optimisation model using an example concerning ropeway systems. Originality/value: This is the first study to simultaneously consider maintenance policy and operational policy in an urban aerial ropeway system, taking up the problem of queuing with particular attention to the unique requirements public transport services. © 2019, Emerald Publishing Limited

Assessment of visual impact due to surface mining with the Lvi method

Surface mining and quarrying typically generate a number of environmental concerns among which landscape alteration is one of the most significant. Although landscape and visual impact does not directly affect public health, it usually generates a negative reaction among potential observers, sometimes influencing the socioeconomic development of the surrounding impact territory. The landscape and visual impact assessment involves individual perceptions, aesthetic tastes and visual comprehension; however, some aspects of landscape modification can be objectively measured in order to quantify the magnitude of change. The article summarizes the results of previous studies focused on the implementation of the Lvi (Level of Visual Impact) method to a variety of cases within the European territory and discusses the adequacy of the method in providing an objective estimation of the visual damage produced by surface mining and quarrying. The visual impact indicator Lvi takes into account two parameters among those physically measurable: the extent of the visible alteration and the chromatic contrast between the color of the bare rock and that of the surrounding landscape. Both parameters can be quantified by processing one or more digital images taken from the most significant viewpoints (public roads, towns, villages, touristic sites, etc.). The article also includes the results of a recent study where the use of a global impact factor LVI to be associated to a given route has been proposed, in order to account for the variability of the visual impact along the route. Other studies proved the visual impact indicator Lvi to be significantly correlated with the subjective perception of potential observers, the results of a test carried out in the University of Cagliari are briefly reported in this article. Some critical aspects regarding the variability of the results on the basis of the shooting conditions (type of camera, season and time of the day, etc.) are discussed, as well as the possibility of developing the assessment procedure as to include the estimate of the ante-operam quality of the impact territory under exam and the number and type of people who are likely to observe the landscape modificatio