An Exploratory Study of Field Failures

Field failures, that is, failures caused by faults that escape the testing phase leading to failures in the field, are unavoidable. Improving verification and validation activities before deployment can identify and timely remove many but not all faults, and users may still experience a number of annoying problems while using their software systems. This paper investigates the nature of field failures, to understand to what extent further improving in-house verification and validation activities can reduce the number of failures in the field, and frames the need of new approaches that operate in the field. We report the results of the analysis of the bug reports of five applications belonging to three different ecosystems, propose a taxonomy of field failures, and discuss the reasons why failures belonging to the identified classes cannot be detected at design time but shall be addressed at runtime. We observe that many faults (70%) are intrinsically hard to detect at design-time

Symptoms of anxiety and depression and family's quality of life in children and adolescents with epilepsy

Introduction We studied children and adolescents with epilepsy (CAWE) and their families to evaluate symptoms of anxiety and depression, quality of life (QoL), and their correlations with epilepsy characteristics. Material and methods The study included 326 (52.5% females) 8 to 18 years old CAWE. Anxiety and depression were assessed with the â\u80\u9cSelf-administered psychiatric scales for children and adolescentsâ\u80\u9d (SAFA), and family's QoL with the parentsâ\u80\u99 report â\u80\u9cImpact of Epilepsy on QoLâ\u80\u9d (IEQoL). Results The CAWE exhibiting abnormal (T â\u89¥ 70) scores were 8.0% in the anxiety scale, 9.2% in the depression scale, and 4.6% in both scales. Social anxiety was the predominant anxiety symptom, while irritable mood and desperation were the most frequent symptoms of depression. Depressive symptoms were associated with parentsâ\u80\u99 complaint of higher worries about the child's condition and future and lower well-being of the family. Severity and duration of the epilepsy and polypharmacy were independent from abnormal scores of anxiety and depression, but were associated with parentsâ\u80\u99 worries about the child's condition and family's well-being. Conclusions Anxiety and depression in CAWE are independent from the characteristics of the disease but are correlated to the lower well-being of the family. A search of these emotional problems is recommended for better care of the patients and their families

Genetic and forensic implications in epilepsy and cardiac arrhythmias. a case series

Epilepsy affects approximately 3 % of the world's population, and sudden death is a significant cause of death in this population. Sudden unexpected death in epilepsy (SUDEP) accounts for up to 17 % of all these cases, which increases the rate of sudden death by 24-fold as compared to the general population. The underlying mechanisms are still not elucidated, but recent studies suggest the possibility that a common genetic channelopathy might contribute to both epilepsy and cardiac disease to increase the incidence of death via a lethal cardiac arrhythmia. We performed genetic testing in a large cohort of individuals with epilepsy and cardiac conduction disorders in order to identify genetic mutations that could play a role in the mechanism of sudden death. Putative pathogenic disease-causing mutations in genes encoding cardiac ion channel were detected in 24 % of unrelated individuals with epilepsy. Segregation analysis through genetic screening of the available family members and functional studies are crucial tasks to understand and to prove the possible pathogenicity of the variant, but in our cohort, only two families were available. Despite further research should be performed to clarify the mechanism of coexistence of both clinical conditions, genetic analysis, applied also in post-mortem setting, could be very useful to identify genetic factors that predispose epileptic patients to sudden death, helping to prevent sudden death in patients with epilepsy

Genetic and forensic implications in epilepsy and cardiac arrhythmias: a case series

Epilepsy affects approximately 3 % of the world’s population, and sudden death is a significant cause of death in this population. Sudden unexpected death in epilepsy (SUDEP) accounts for up to 17 % of all these cases, which increases the rate of sudden death by 24-fold as compared to the general population. The underlying mechanisms are still not elucidated, but recent studies suggest the possibility that a common genetic channelopathy might contribute to both epilepsy and cardiac disease to increase the incidence of death via a lethal cardiac arrhythmia. We performed genetic testing in a large cohort of individuals with epilepsy and cardiac conduction disorders in order to identify genetic mutations that could play a role in the mechanism of sudden death. Putative pathogenic disease-causing mutations in genes encoding cardiac ion channel were detected in 24 % of unrelated individuals with epilepsy. Segregation analysis through genetic screening of the available family members and functional studies are crucial tasks to understand and to prove the possible pathogenicity of the variant, but in our cohort, only two families were available. Despite further research should be performed to clarify the mechanism of coexistence of both clinical conditions, genetic analysis, applied also in post-mortem setting, could be very useful to identify genetic factors that predispose epileptic patients to sudden death, helping to prevent sudden death in patients with epilepsy

Association of intronic variants of the <i>KCNAB1</i> gene with lateral temporal epilepsy

The KCNAB1 gene is a candidate susceptibility factor for lateral temporal epilepsy (LTE) because of its functional interaction with LGI1, the gene responsible for the autosomal dominant form of LTE. We investigated association between polymorphic variants across the KCNAB1 gene and LTE. The allele and genotype frequencies of 14 KCNAB1 intronic SNPs were determined in 142 Italian LTE patients and 104 healthy controls and statistically evaluated. Single SNP analysis revealed one SNP (rs992353) located near the 3&#x2032;end of KCNAB1 slightly associated with LTE after multiple testing correction (odds ratio = 2.25; 95% confidence interval 1.26-4.04; P = 0.0058). Haplotype analysis revealed two haplotypes with frequencies higher in cases than in controls, and these differences were statistically significant after permutation tests (Psim = 0.047 and 0.034). One of these haplotypes was shown to confer a high risk for the syndrome (odds ratio = 12.24; 95% confidence interval 1.32-113.05) by logistic regression analysis. These results support KCNAB1 as a susceptibility gene for LTE, in agreement with previous studies showing that this gene may alter susceptibility to focal epilepsy

Association of intronic variants of the KCNAB1 gene with lateral temporal epilepsy.

none29The KCNAB1 gene is a candidate susceptibility factor for lateral temporal epilepsy (LTE) because of its functional interaction with LGI1, the gene responsible for the autosomal dominant form of LTE. We investigated association between polymorphic variants across the KCNAB1 gene and LTE. The allele and genotype frequencies of 14 KCNAB1 intronic SNPs were determined in 142 Italian LTE patients and 104 healthy controls and statistically evaluated. Single SNP analysis revealed one SNP (rs992353) located near the 3'end of KCNAB1 slightly associated with LTE after multiple testing correction (odds ratio=2.25; 95\% confidence interval 1.26-4.04; P=0.0058). Haplotype analysis revealed two haplotypes with frequencies higher in cases than in controls, and these differences were statistically significant after permutation tests (Psim=0.047 and 0.034). One of these haplotypes was shown to confer a high risk for the syndrome (odds ratio=12.24; 95\% confidence interval 1.32-113.05) by logistic regression analysis. These results support KCNAB1 as a susceptibility gene for LTE, in agreement with previous studies showing that this gene may alter susceptibility to focal epilepsy.G. Busolin;S. Malacrida;F. Bisulli;P. Striano;C. D. Bonaventura;G. Egeo;E. Pasini;V. Cianci;E. Ferlazzo;A. Bianchi;G. Coppola;M. Elia;O. Mecarelli;G. Gobbi;S. Casellato;M. Marchini;S. Binelli;E. Freri;T. Granata;A. Posar;A. Parmeggiani;P. Vigliano;C. Boniver;U. Aguglia;S. Striano;P. Tinuper;A. T. Giallonardo;R. Michelucci;C. NobileG., Busolin; S., Malacrida; F., Bisulli; Striano, Pasquale; C. D., Bonaventura; G., Egeo; E., Pasini; V., Cianci; E., Ferlazzo; A., Bianchi; G., Coppola; M., Elia; O., Mecarelli; G., Gobbi; S., Casellato; M., Marchini; S., Binelli; E., Freri; T., Granata; A., Posar; A., Parmeggiani; P., Vigliano; C., Boniver; U., Aguglia; S., Striano; P., Tinuper; A. T., Giallonardo; R., Michelucci; C., Nobil

Association of intronic variants of the KCNAB1 gene with lateral temporal epilepsy

The KCNAB1 gene is a candidate susceptibility factor for lateral temporal epilepsy (LTE) because of its functional interaction with LGI1, the gene responsible for the autosomal dominant form of LTE. We investigated association between polymorphic variants across the KCNAB1 gene and LTE. The allele and genotype frequencies of 14 KCNAB1 intronic SNPs were determined in 142 Italian LTE patients and 104 healthy controls and statistically evaluated. Single SNP analysis revealed one SNP (rs992353) located near the 3'end of KCNAB1 slightly associated with LTE after multiple testing correction (odds ratio = 2.25; 95% confidence interval 1.26-4.04; P=0.0058). Haplotype analysis revealed two haplotypes with frequencies higher in cases than in controls, and these differences were statistically significant after permutation tests (Psim = 0.047 and 0.034). One of these haplotypes was shown to confer a high risk for the syndrome (odds ratio = 12.24; 95% confidence interval 1.32-113.05) by logistic regression analysis. These results support KCNAB1 as a susceptibility gene for LTE, in agreement with previous studies showing that this gene may alter susceptibility to focal epilepsy. (C) 2011 Elsevier B.V. All rights reserved

Dissecting the genetics of spectrum of Epilepsies with Eyelid Myoclonia by exome sequencing

OBJECTIVES: Epilepsy with Eyelid Myoclonia (EEM) spectrum, is a generalized form of epilepsy characterized by eyelid myoclonia with or without absences, eye closure-induced seizures with EEG paroxysms, and photosensitivity. Based on the specific clinical features, age of onset and familial occurrence, a genetic cause has been postulated. Pathogenic variants in CHD2, SYNGAP1, NEXMIF and RORB and GABRA1 have been reported in individuals with photosensitivity and eyelid myoclonia, but whether other genes are also involved, or a single gene is uniquely linked with EEM, or its subtypes, is not yet known. We aimed to dissect the genetic aetiology of EEM. METHODS: we studied a cohort of 105 individuals by using whole-exome sequencing. Individuals were divided into two groups: EEM- (isolated EEM) and EEM+ (EEM accompanied by intellectual disability, ID, or any other neurodevelopmental/psychiatric disorder) RESULTS: We identified nine variants classified as pathogenic/likely pathogenic in the entire cohort (8.57%); among these eight (five in CHD2, one in NEXMIF, one in SYNGAP1 and one in TRIM8) were found in the EEM+ sub-cohort (28.57%). Only one variant (IFIH1) was found in the EEM- sub-cohort (1.29%); however, since the phenotype of the proband did not fit with published data, additional evidence is needed before considering IFIH1 variants and EEM- an established association. Burden analysis did not identify any single burdened gene or gene set. SIGNIFICANCE: Our results suggest that for EEM, as for many other epilepsies, the identification of a genetic cause is more likely with co-morbid ID and/or other neurodevelopmental disorders. Pathogenic variants were mostly found in CHD2 and the association of CHD2-EEM+ can now be considered a reasonable gene-disease association. We provide further evidence to strengthen the association of EEM+ with NEXMIF and SYNGAP1. Possible new associations between EEM+ and TRIM8, and EEM- and IFIH1, are also reported. While we provided robust evidence for gene variants associated with EEM+, the core genetic aetiology of EEM- remains to be elucidated

Dissecting the genetics of spectrum of Epilepsies with Eyelid Myoclonia by exome sequencing

Objectives: Epilepsy with Eyelid Myoclonia (EEM) spectrum, is a generalized form of epilepsy characterized by eyelid myoclonia with or without absences, eye closure-induced seizures with EEG paroxysms, and photosensitivity. Based on the specific clinical features, age of onset and familial occurrence, a genetic cause has been postulated. Pathogenic variants in CHD2, SYNGAP1, NEXMIF and RORB and GABRA1 have been reported in individuals with photosensitivity and eyelid myoclonia, but whether other genes are also involved, or a single gene is uniquely linked with EEM, or its subtypes, is not yet known. We aimed to dissect the genetic aetiology of EEM. Methods: we studied a cohort of 105 individuals by using whole-exome sequencing. Individuals were divided into two groups: EEM- (isolated EEM) and EEM+ (EEM accompanied by intellectual disability, ID, or any other neurodevelopmental/psychiatric disorder) RESULTS: We identified nine variants classified as pathogenic/likely pathogenic in the entire cohort (8.57%); among these eight (five in CHD2, one in NEXMIF, one in SYNGAP1 and one in TRIM8) were found in the EEM+ sub-cohort (28.57%). Only one variant (IFIH1) was found in the EEM- sub-cohort (1.29%); however, since the phenotype of the proband did not fit with published data, additional evidence is needed before considering IFIH1 variants and EEM- an established association. Burden analysis did not identify any single burdened gene or gene set. Significance: Our results suggest that for EEM, as for many other epilepsies, the identification of a genetic cause is more likely with co-morbid ID and/or other neurodevelopmental disorders. Pathogenic variants were mostly found in CHD2 and the association of CHD2-EEM+ can now be considered a reasonable gene-disease association. We provide further evidence to strengthen the association of EEM+ with NEXMIF and SYNGAP1. Possible new associations between EEM+ and TRIM8, and EEM- and IFIH1, are also reported. While we provided robust evidence for gene variants associated with EEM+, the core genetic aetiology of EEM- remains to be elucidated