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See detailIncluding gaming disorder in the ICD-11: The need to do so from a clinical and public health perspective.
Rumpf, Hans-Jurgen; Achab, Sophia; Billieux, Joël UL et al

in Journal of behavioral addictions (in press)

The proposed introduction of gaming disorder (GD) in the 11th revision of the International Classification of Diseases (ICD-11) developed by the World Health Organization (WHO) has led to a lively debate ... [more ▼]

The proposed introduction of gaming disorder (GD) in the 11th revision of the International Classification of Diseases (ICD-11) developed by the World Health Organization (WHO) has led to a lively debate over the past year. Besides the broad support for the decision in the academic press, a recent publication by van Rooij et al. (2018) repeated the criticism raised against the inclusion of GD in ICD-11 by Aarseth et al. (2017). We argue that this group of researchers fails to recognize the clinical and public health considerations, which support the WHO perspective. It is important to recognize a range of biases that may influence this debate; in particular, the gaming industry may wish to diminish its responsibility by claiming that GD is not a public health problem, a position which maybe supported by arguments from scholars based in media psychology, computer games research, communication science, and related disciplines. However, just as with any other disease or disorder in the ICD-11, the decision whether or not to include GD is based on clinical evidence and public health needs. Therefore, we reiterate our conclusion that including GD reflects the essence of the ICD and will facilitate treatment and prevention for those who need it. [less ▲]

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See detailA Natural Language Programming Approach for Requirements-based Security Testing
Mai, Xuan Phu UL; Pastore, Fabrizio UL; Göknil, Arda UL et al

in Mai, Xuan Phu; Pastore, Fabrizio; Göknil, Arda (Eds.) et al A Natural Language Programming Approach for Requirements-based Security Testing (in press)

To facilitate communication among stakeholders, software security requirements are typically written in natural language and capture both positive requirements (i.e., what the system is supposed to do to ... [more ▼]

To facilitate communication among stakeholders, software security requirements are typically written in natural language and capture both positive requirements (i.e., what the system is supposed to do to ensure security) and negative requirements (i.e., undesirable behavior undermining security). In this paper, we tackle the problem of automatically generat- ing executable security test cases from security requirements in natural language (NL). More precisely, since existing approaches for the generation of test cases from NL requirements verify only positive requirements, we focus on the problem of generating test cases from negative requirements. We propose, apply and assess Misuse Case Programming (MCP), an approach that automatically generates security test cases from misuse case specifications (i.e., use case specifications capturing the behavior of malicious users). MCP relies on natural language processing techniques to extract the concepts (e.g., inputs and activities) appearing in requirements specifications and generates executable test cases by matching the extracted concepts to the members of a provided test driver API. MCP has been evaluated in an industrial case study, which provides initial evidence of the feasibility and benefits of the approach. [less ▲]

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See detailPrevalence and Correlates of Problematic Online Gaming: a Systematic Review of the Evidence Published in Chinese
Long, Jiang; Liu, Tieqiao; Liu, Yueheng et al

in Current Addiction Reports (in press)

Purpose of Review With the ongoing debate about whether problematic online gaming (POG) constitutes a genuine mental disorder, it is important for all available evidence in the field to be accessible. In ... [more ▼]

Purpose of Review With the ongoing debate about whether problematic online gaming (POG) constitutes a genuine mental disorder, it is important for all available evidence in the field to be accessible. In this systematic review, we summarize the numerous results related to POG published in Chinese in order to make them more accessible to the international community. Recent Findings We identified 36 relevant studies published in Chinese (7 epidemiological, 21 related to psychological factors, and 8 related to neurocognitive exploration, involving 362,328 participants in total). According to the literature, the prevalence rates of POG in China range from 3.5 to 17%, which is higher than those reported worldwide. Overall, the data published in Chinese are consistent with the international literature. Some distinctive findings emerged, however, in particular in relation to familial, scholastic, and social factors; cognitive impairments; and functional changes in neural circuits. Summary This review is the first to render available articles on POG in Chinese for the international community, which could contribute to the current debate on the status of POG as a genuine mental health condition. Crucially, findings from the Chinese literature often resulted from studies conducted on large random or clinical samples. This is important because a repeated criticism about the recognition of POG as a genuine disorder is the fact that the evidence-based results rely heavily on convenience samples of nonclinical participants. [less ▲]

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See detailAssessing binge-watching behaviors: Development and validation of the “Watching TV Series Motives” and “Binge-Watching Engagement and Symptoms” questionnaires
Flayelle, Maèva UL; Canale, Natale; Vögele, Claus UL et al

in Computers in Human Behavior (in press)

The widespread practice of binge-watching (i.e. watching multiple episodes of a TV series in one session) recently generated concerns about associated negative outcomes. Its psychological investigation ... [more ▼]

The widespread practice of binge-watching (i.e. watching multiple episodes of a TV series in one session) recently generated concerns about associated negative outcomes. Its psychological investigation, however, remains fragmentary. Based on the previous phenomenological investigation of TV series watching, we developed and validated two original assessment instruments, assessing TV series watching motives and binge-watching engagement and symptoms, respectively. Preliminary items were created for each questionnaire, and a focus group with TV series viewers was conducted and analyzed to generate the final instruments. The questionnaires were then administered via an online survey (N=6556), together with complementary measures of affect, problematic Internet use and substance use. Exploratory and confirmatory factor analyses, along with correlational analyses, were performed to examine both structural and external validity of the scales. The factorial analyses resulted in a 4-factor model (i.e. emotional enhancement, enrichment, coping-escapism and social) for the Watching TV Series Motives Questionnaire (WTSMQ), and in a 7-factor model (i.e. engagement, positive emotions, desire-savoring, pleasure preservation, binge-watching, dependency and loss of control) for the Binge-Watching Engagement and Symptoms Questionnaire (BWESQ). The results suggest good psychometric properties for both scales. The current study thus provides theoretically-driven and psychometrically sound instruments for further research on binge-watching behaviors [less ▲]

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See detailArbeitslosigkeit für Lehrabgänger problematisch
Sacchi, Stefan; Shi, Lulu P.; Imdorf, Christian et al

in Die Volkswirtschaft (in press)

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See detailInternationale Besteuerung der digitalen Wirtschaft: EU- und OECD-Vorschläge
Sinnig, Julia UL

in Taeger, Jürgen (Ed.) Tagungsband Herbstakademie 2018: Rechtsfragen digitaler Transformationen - Gestaltung digitaler Veränderungsprozesse durch Recht (in press)

Im März 2018 stellten sowohl die Organisation für wirtschaftliche Zusammenarbeit und Entwicklung (OECD) als auch die Europäische Union (EU) Zwischenergebnisse ihrer Arbeit im Bereich der ... [more ▼]

Im März 2018 stellten sowohl die Organisation für wirtschaftliche Zusammenarbeit und Entwicklung (OECD) als auch die Europäische Union (EU) Zwischenergebnisse ihrer Arbeit im Bereich der Ertragsbesteuerung digitalisierter Geschäftsaktivitäten vor. Während die OECD keine konkrete Empfehlung zur Anpassung bestehender Vorschriften des internationalen Steuerrechts aussprach, stellte die Europäische Kommission sowohl eine langfristige Maßnahme – eine Anpassung des Betriebsstättenkonzepts zugunsten einer sog. signifikanten digitalen Präsenz – als auch einen kurzfristigen Besteuerungsvorschlag – eine sog. Digitalsteuer – vor. Dieser Beitrag knüpft an den Vortrag der Verfasserin in Heidelberg anlässlich der Herbstakademie 2017 an. [less ▲]

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See detailElectrophysiological correlates of emotional crossmodal processing in binge drinking.
Lannoy, Severine; D'Hondt, Fabien; Dormal, Valerie et al

in Cognitive, affective & behavioral neuroscience (in press)

Emotional crossmodal integration (i.e., multisensorial decoding of emotions) is a crucial process that ensures adaptive social behaviors and responses to the environment. Recent evidence suggests that in ... [more ▼]

Emotional crossmodal integration (i.e., multisensorial decoding of emotions) is a crucial process that ensures adaptive social behaviors and responses to the environment. Recent evidence suggests that in binge drinking-an excessive alcohol consumption pattern associated with psychological and cerebral deficits-crossmodal integration is preserved at the behavioral level. Although some studies have suggested brain modifications during affective processing in binge drinking, nothing is known about the cerebral correlates of crossmodal integration. In the current study, we asked 53 university students (17 binge drinkers, 17 moderate drinkers, 19 nondrinkers) to perform an emotional crossmodal task while their behavioral and neurophysiological responses were recorded. Participants had to identify happiness and anger in three conditions (unimodal, crossmodal congruent, crossmodal incongruent) and two modalities (face and/or voice). Binge drinkers did not significantly differ from moderate drinkers and nondrinkers at the behavioral level. However, widespread cerebral modifications were found at perceptual (N100) and mainly at decisional (P3b) stages in binge drinkers, indexed by slower brain processing and stronger activity. These cerebral modifications were mostly related to anger processing and crossmodal integration. This study highlights higher electrophysiological activity in the absence of behavioral deficits, which could index a potential compensation process in binge drinkers. In line with results found in severe alcohol-use disorders, these electrophysiological findings show modified anger processing, which might have a deleterious impact on social functioning. Moreover, this study suggests impaired crossmodal integration at early stages of alcohol-related disorders. [less ▲]

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See detailValuing Creativity, Feeling Overworked and Working Hours: Male Workers and the New Spirit of Capitalism
Samuel, Robin UL; Kanji, Shireen

in Time & Society (in press)

Boltanski and Chiapello (2005) argued that creativity is a required attribute of managers emanating from the ideology of the ‘New Spirit of Capitalism’. Ideology provides the justification for work ... [more ▼]

Boltanski and Chiapello (2005) argued that creativity is a required attribute of managers emanating from the ideology of the ‘New Spirit of Capitalism’. Ideology provides the justification for work practices and brings material consequences in relation to the experience of time. This article explores both the ideology and the links between the ideological and the experience of time by assessing whether male managers prioritise creativity and whether this is related to their working hours, driving them to work longer hours than other workers and longer hours than they actually want. Men’s dominant position in work organisations puts them at the centre of this exploration. Using multilevel logistic and linear models on 2010 data from the European Social Survey (N = 7049), we show that male managers prioritise creativity more than other workers do. There are consequences for the experience of time as valuing creativity in combination with being a manager increases working hours above the large and significant effect of being a manager. The feeling of overwork is raised independently for those who value creativity and for those who are managers. [less ▲]

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See detailAccess to Medical Technologies: Do Gender and Social Capital Matter?
Geraudel, Mickaël UL; Gundolf, Katherine; Cesinger, Beate et al

in Management International = International Management = Gestión Internacional (in press)

We explore the relationship between the characteristics of social capital, the speed of access to medical technologies and the role of gender in a private practice context. Our findings from a sample of ... [more ▼]

We explore the relationship between the characteristics of social capital, the speed of access to medical technologies and the role of gender in a private practice context. Our findings from a sample of 98 German private practitioners show that: (a) being a woman has an overall negative impact on the speed of access to medical technologies; (b) private practitioners with strong social network ties obtain quicker access to medical technologies than do those with weak ties; (c) men relying on their weak ties perform better than women who do so. In contrast, we observe that women relying on strong ties outperform their male counterparts in terms of speed of access to medical technologies. [less ▲]

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See detailStriking a balance between competitiveness and social fairness: what can we expect from the European Pillar of Social Rights?
Muñoz, Susana UL

in Chiocchetti, Paolo; Allemand, Frédéric (Eds.) Competitiveness and Solidarity in the European Union: Interdisciplinary Perspectives (2019)

The solemnly proclaimed European Pillar of Social Rights provides a meaningful response to the process of building a deeper, fairer European Union in the aftermath of the crisis. This chapter aims to ... [more ▼]

The solemnly proclaimed European Pillar of Social Rights provides a meaningful response to the process of building a deeper, fairer European Union in the aftermath of the crisis. This chapter aims to provide a critical assessment of the nature, scope, rationale, purpose, content and effectiveness of the Pillar in the light of its potential contribution to foster social fairness and competitiveness in the EU. The Pillar complements and develops the EU’s social acquis and reinforces standards which may provide a fairer and more socially-balanced competitiveness in the EU. Progress has been made, but further efforts are needed to build a sense of common purpose to strengthen the social foundations of the Union. [less ▲]

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See detailSequential Resource Distribution Technique for Multi-User OFDM-SWIPT based Cooperative Networks
Gautam, Sumit UL; Lagunas, Eva UL; Chatzinotas, Symeon UL et al

Scientific Conference (2018, December)

In this paper, we investigate resource allocation and relay selection in a dual-hop orthogonal frequency division multiplexing (OFDM)-based multi-user network where amplify-and-forward (AF) enabled relays ... [more ▼]

In this paper, we investigate resource allocation and relay selection in a dual-hop orthogonal frequency division multiplexing (OFDM)-based multi-user network where amplify-and-forward (AF) enabled relays facilitate simultaneous wireless information and power transfer (SWIPT) to the end-users. In this context, we address an optimization problem to maximize the end-users’ sum-rate subjected to transmit power and harvested energy constraints. Furthermore, the problem is formulated for both time-switching (TS) and power-splitting (PS) SWIPT schemes.We aim at optimizing the users’ SWIPT splitting factors as well as sub-carrier–destination assignment, sub-carrier pairing, and relay–destination coupling metrics. This kind of joint evaluation is combinatorial in nature with non-linear structure involving mixed-integer programming. In this vein, we propose a sub-optimal low complex sequential resource distribution (SRD) method to solve the aforementioned problem. The performance of the proposed SRD technique is compared with a semi-random resource allocation and relay selection approach. Simulation results reveal the benefits of the proposed design under several parameter values with various operating conditions to illustrate the efficiency of SWIPT schemes for the proposed techniques. [less ▲]

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See detailHITECS: A UML Profile and Analysis Framework for Hardware-in-the-Loop Testing of Cyber Physical Systems
Shin, Seung Yeob UL; Chaouch, Karim UL; Nejati, Shiva UL et al

in Proceedings of ACM/IEEE 21st International Conference on Model Driven Engineering Languages and Systems (MODELS’18) (2018, October)

Hardware-in-the-loop (HiL) testing is an important step in the development of cyber physical systems (CPS). CPS HiL test cases manipulate hardware components, are time-consuming and their behaviors are ... [more ▼]

Hardware-in-the-loop (HiL) testing is an important step in the development of cyber physical systems (CPS). CPS HiL test cases manipulate hardware components, are time-consuming and their behaviors are impacted by the uncertainties in the CPS environment. To mitigate the risks associated with HiL testing, engineers have to ensure that (1) HiL test cases are well-behaved, i.e., they implement valid test scenarios and do not accidentally damage hardware, and (2) HiL test cases can execute within the time budget allotted to HiL testing. This paper proposes an approach to help engineers systematically specify and analyze CPS HiL test cases. Leveraging the UML profile mechanism, we develop an executable domain-specific language, HITECS, for HiL test case specification. HITECS builds on the UML Testing Profile (UTP) and the UML action language (Alf). Using HITECS, we provide analysis methods to check whether HiL test cases are well-behaved, and to estimate the execution times of these test cases before the actual HiL testing stage. We apply HITECS to an industrial case study from the satellite domain. Our results show that: (1) HITECS is feasible to use in practice; (2) HITECS helps engineers define more complete and effective well-behavedness assertions for HiL test cases, compared to when these assertions are defined without systematic guidance; (3) HITECS verifies in practical time that HiL test cases are well-behaved; and (4) HITECS accurately estimates HiL test case execution times. [less ▲]

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See detailEnabling Model Testing of Cyber-Physical Systems
Gonzalez Perez, Carlos Alberto UL; Varmazyar, Mojtaba UL; Nejati, Shiva UL et al

in Proceedings of ACM/IEEE 21st International Conference on Model Driven Engineering Languages and Systems (MODELS’18) (2018, October)

Applying traditional testing techniques to Cyber-Physical Systems (CPS) is challenging due to the deep intertwining of software and hardware, and the complex, continuous interactions between the system ... [more ▼]

Applying traditional testing techniques to Cyber-Physical Systems (CPS) is challenging due to the deep intertwining of software and hardware, and the complex, continuous interactions between the system and its environment. To alleviate these challenges we propose to conduct testing at early stages and over executable models of the system and its environment. Model testing of CPSs is however not without difficulties. The complexity and heterogeneity of CPSs renders necessary the combination of different modeling formalisms to build faithful models of their different components. The execution of CPS models thus requires an execution framework supporting the co-simulation of different types of models, including models of the software (e.g., SysML), hardware (e.g., SysML or Simulink), and physical environment (e.g., Simulink). Furthermore, to enable testing in realistic conditions, the co-simulation process must be (1) fast, so that thousands of simulations can be conducted in practical time, (2) controllable, to precisely emulate the expected runtime behavior of the system and, (3) observable, by producing simulation data enabling the detection of failures. To tackle these challenges, we propose a SysML-based modeling methodology for model testing of CPSs, and an efficient SysML-Simulink co-simulation framework. Our approach was validated on a case study from the satellite domain. [less ▲]

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See detailPreventing and Resolving Conflicts of Jurisdiction in EU Criminal Law
Ligeti, Katalin UL; Robinson, Gavin UL; European Law Institute

Book published by Oxford University Press (2018)

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See detailTUNA: TUning Naturalness-based Analysis
Jimenez, Matthieu UL; Cordy, Maxime UL; Le Traon, Yves UL et al

in 34th IEEE International Conference on Software Maintenance and Evolution, Madrid, Spain, 26-28 September 2018 (2018, September 26)

Natural language processing techniques, in particular n-gram models, have been applied successfully to facilitate a number of software engineering tasks. However, in our related ICSME ’18 paper, we have ... [more ▼]

Natural language processing techniques, in particular n-gram models, have been applied successfully to facilitate a number of software engineering tasks. However, in our related ICSME ’18 paper, we have shown that the conclusions of a study can drastically change with respect to how the code is tokenized and how the used n-gram model is parameterized. These choices are thus of utmost importance, and one must carefully make them. To show this and allow the community to benefit from our work, we have developed TUNA (TUning Naturalness-based Analysis), a Java software artifact to perform naturalness-based analyses of source code. To the best of our knowledge, TUNA is the first open- source, end-to-end toolchain to carry out source code analyses based on naturalness. [less ▲]

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See detailKünstliche Intelligenz - die nächste Revolution (The Artificial Intelligence Revolution)
Glauner, Patrick UL

in Plugmann, Philipp (Ed.) Innovationsumgebungen gestalten (2018)

Es vergeht mittlerweile kein Tag, an welchem wir nicht von künstlicher Intelligenz (KI) (Artificial Intelligence (AI)) hören: autonom fahrende Autos, Spamfilter, Siri, Schachcomputer, Killerroboter und ... [more ▼]

Es vergeht mittlerweile kein Tag, an welchem wir nicht von künstlicher Intelligenz (KI) (Artificial Intelligence (AI)) hören: autonom fahrende Autos, Spamfilter, Siri, Schachcomputer, Killerroboter und vieles mehr. Was genau steckt jedoch hinter KI? In diesem Kapitel bieten wir einen Überblick zu KI und stellen moderne KI-Anwendungen vor. Anschließend stellen wir ein Innovationsökosystem vor, in dem wir momentan ein Forschungsprojekt zur Erkennung von Elektrizitätsdiebstahl in Entwicklungs- und Schwellenländern mit Hilfe von KI betreiben. [less ▲]

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See detailOn the impact of tokenizer and parameters on N-gram based Code Analysis
Jimenez, Matthieu UL; Cordy, Maxime UL; Le Traon, Yves UL et al

Scientific Conference (2018, September)

Recent research shows that language models, such as n-gram models, are useful at a wide variety of software engineering tasks, e.g., code completion, bug identification, code summarisation, etc. However ... [more ▼]

Recent research shows that language models, such as n-gram models, are useful at a wide variety of software engineering tasks, e.g., code completion, bug identification, code summarisation, etc. However, such models require the appropriate set of numerous parameters. Moreover, the different ways one can read code essentially yield different models (based on the different sequences of tokens). In this paper, we focus on n- gram models and evaluate how the use of tokenizers, smoothing, unknown threshold and n values impact the predicting ability of these models. Thus, we compare the use of multiple tokenizers and sets of different parameters (smoothing, unknown threshold and n values) with the aim of identifying the most appropriate combinations. Our results show that the Modified Kneser-Ney smoothing technique performs best, while n values are depended on the choice of the tokenizer, with values 4 or 5 offering a good trade-off between entropy and computation time. Interestingly, we find that tokenizers treating the code as simple text are the most robust ones. Finally, we demonstrate that the differences between the tokenizers are of practical importance and have the potential of changing the conclusions of a given experiment. [less ▲]

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See detailModel-driven Run-time Enforcement of Complex Role-based Access Control Policies
Ben Fadhel, Ameni UL; Bianculli, Domenico UL; Briand, Lionel UL

in Proceeding of the 2018 33rd ACM/IEEE International Conference on Automated Software Engineering (ASE ’18) (2018, September)

A Role-based Access Control (RBAC) mechanism prevents unauthorized users to perform an operation, according to authorization policies which are defined on the user’s role within an enterprise. Several ... [more ▼]

A Role-based Access Control (RBAC) mechanism prevents unauthorized users to perform an operation, according to authorization policies which are defined on the user’s role within an enterprise. Several models have been proposed to specify complex RBAC policies. However, existing approaches for policy enforcement do not fully support all the types of policies that can be expressed in these models, which hinders their adoption among practitioners. In this paper we propose a model-driven enforcement framework for complex policies captured by GemRBAC+CTX, a comprehensive RBAC model proposed in the literature. We reduce the problem of making an access decision to checking whether a system state (from an RBAC point of view), expressed as an instance of the GemRBAC+CTX model, satisfies the constraints corresponding to the RBAC policies to be enforced at run time. We provide enforcement algorithms for various types of access requests and events, and a prototype tool (MORRO) implementing them. We also show how to integrate MORRO into an industrial Web application. The evaluation results show the applicability of our approach on a industrial system and its scalability with respect to the various parameters characterizing an AC configuration. [less ▲]

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See detailAn Imperialist Competitive Algorithm for a Real-World Flexible Job Shop Scheduling Problem
Tessaro Lunardi, Willian UL; Voos, Holger UL; Cherri, Luiz Henrique

in 23rd IEEE International Conference on Emerging Technologies and Factory Automation, Torino, Italy, September 4-7, 2018 (2018, September)

Traditional planning and scheduling techniques still hold important roles in modern smart scheduling systems. Realistic features present in modern manufacturing systems need to be incorporated into these ... [more ▼]

Traditional planning and scheduling techniques still hold important roles in modern smart scheduling systems. Realistic features present in modern manufacturing systems need to be incorporated into these techniques. The real-world problem addressed here is an extension of flexible job shop scheduling problem and is issued from the modern printing and boarding industry. The precedence between operations of each job is given by an arbitrary directed acyclic graph rather than a linear order. In this paper, we extend the traditional FJSP solutions representation to address the parallel operations. We propose an imperialist competitive algorithm for the problem. Several instances are used for the experiments and the results show that, for the considered instances, the proposed algorithm is faster and found better or equal solutions compared to the state-of-the-art algorithms. [less ▲]

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See detailRare coding variants in genes encoding GABAA receptors in genetic generalised epilepsies: an exome-based case-control study
May, Patrick UL; Girard, Simon; Harrer, Merle et al

in Lancet Neurology (2018), 17(8), 699-708

Background Genetic generalised epilepsy is the most common type of inherited epilepsy. Despite a high concordance rate of 80% in monozygotic twins, the genetic background is still poorly understood. We ... [more ▼]

Background Genetic generalised epilepsy is the most common type of inherited epilepsy. Despite a high concordance rate of 80% in monozygotic twins, the genetic background is still poorly understood. We aimed to investigate the burden of rare genetic variants in genetic generalised epilepsy. Methods For this exome-based case-control study, we used three different genetic generalised epilepsy case cohorts and three independent control cohorts, all of European descent. Cases included in the study were clinically evaluated for genetic generalised epilepsy. Whole-exome sequencing was done for the discovery case cohort, a validation case cohort, and two independent control cohorts. The replication case cohort underwent targeted next-generation sequencing of the 19 known genes encoding subunits of GABAA receptors and was compared to the respective GABAA receptor variants of a third independent control cohort. Functional investigations were done with automated two-microelectrode voltage clamping in Xenopus laevis oocytes. Findings Statistical comparison of 152 familial index cases with genetic generalised epilepsy in the discovery cohort to 549 ethnically matched controls suggested an enrichment of rare missense (Nonsyn) variants in the ensemble of 19 genes encoding GABAA receptors in cases (odds ratio [OR] 2·40 [95% CI 1·41–4·10]; pNonsyn=0·0014, adjusted pNonsyn=0·019). Enrichment for these genes was validated in a whole-exome sequencing cohort of 357 sporadic and familial genetic generalised epilepsy cases and 1485 independent controls (OR 1·46 [95% CI 1·05–2·03]; pNonsyn=0·0081, adjusted pNonsyn=0·016). Comparison of genes encoding GABAA receptors in the independent replication cohort of 583 familial and sporadic genetic generalised epilepsy index cases, based on candidate-gene panel sequencing, with a third independent control cohort of 635 controls confirmed the overall enrichment of rare missense variants for 15 GABAA receptor genes in cases compared with controls (OR 1·46 [95% CI 1·02–2·08]; pNonsyn=0·013, adjusted pNonsyn=0·027). Functional studies for two selected genes (GABRB2 and GABRA5) showed significant loss-of-function effects with reduced current amplitudes in four of seven tested variants compared with wild-type receptors. Interpretation Functionally relevant variants in genes encoding GABAA receptor subunits constitute a significant risk factor for genetic generalised epilepsy. Examination of the role of specific gene groups and pathways can disentangle the complex genetic architecture of genetic generalised epilepsy. [less ▲]

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