Lesion topography and microscopic white matter tract damage contribute to cognitive impairment in symptomatic carotid artery disease

Purpose: To investigate associations between neuroimaging markers of cerebrovascular disease, including lesion topography and extent and severity of strategic and global cerebral tissue injury, and cognition in carotid artery disease (CAD). Materials and Methods: All participants gave written informed consent to undergo brain magnetic resonance imaging and the Addenbrooke’s Cognitive Examination–Revised. One hundred eight patients with symptomatic CAD but no dementia were included, and a score less than 82 represented cognitive impairment. Group comparison and interrelations between global cognitive and fluency performance, lesion topography, and ultrastructural damage were assessed with voxel-based statistics. Associations between cognition, medial temporal lobe atrophy (MTA), lesion volumes, and global white matter ultrastructural damage indexed as increased mean diffusivity were tested with regression analysis by controlling for age. Diagnostic accuracy of imaging markers selected from a multivariate prediction model was tested with receiver operating characteristic analysis. Results: Cognitively impaired patients (n = 53 [49.1%], classified as having probable vascular cognitive disorder) were older than nonimpaired patients (P = .027) and had more frequent MTA (P<.001), more cortical infarctions (P = .016), and larger volumes of acute (P = .028) and chronic (P = .009) subcortical ischemic lesions. Lesion volumes did not correlate with global cognitive performance (lacunar infarctions, P = .060; acute lesions, P = .088; chronic subcortical ischemic lesions, P = .085). In contrast, cognitive performance correlated with presence of chronic ischemic lesions within the interhemispheric tracts and thalamic radiation (P< .05, false discovery rate corrected). Skeleton mean diffusivity showed the closest correlation with cognition (R2 = 0.311, P< .001) and promising diagnostic accuracy for vascular cognitive disorder (area under the curve, 0.82 [95% confidence interval: 0.75, 0.90]). Findings were confirmed in subjects with a low risk of preclinical Alzheimer disease indexed by the absence of MTA (n = 85). Conclusion: Subcortical white matter ischemic lesion locations and severity of ultrastructural tract damage contribute to cognitive impairment in symptomatic CAD, which suggests that subcortical disconnection within large-scale cognitive neural networks is a key mechanism of vascular cognitive disorder

Optimal iterative methods for finding multiple roots of nonlinear equations using free parameters

[EN] In this paper, we propose a family of optimal eighth order convergent iterative methods for multiple roots with known multiplicity with the introduction of two free parameters and three univariate weight functions. Also numerical experiments have applied to a number of academical test functions and chemical problems for different special schemes from this family that satisfies the conditions given in convergence result.This research was partially supported by Ministerio de Economia y Competitividad MTM2014-52016-C02-2-P and Generalitat Valenciana PROMETEO/2016/089.Zafar, F.; Cordero Barbero, A.; Quratulain, R.; Torregrosa Sánchez, JR. (2018). Optimal iterative methods for finding multiple roots of nonlinear equations using free parameters. Journal of Mathematical Chemistry. 56(7):1884-1901. https://doi.org/10.1007/s10910-017-0813-1S18841901567R. Behl, A. Cordero, S.S. Motsa, J.R. Torregrosa, On developing fourth-order optimal families of methods for multiple roots and their dynamics. Appl. Math. Comput. 265(15), 520–532 (2015)R. Behl, A. Cordero, S.S. Motsa, J.R. Torregrosa, V. Kanwar, An optimal fourth-order family of methods for multiple roots and its dynamics. Numer. Algor. 71(4), 775–796 (2016)R. Behl, A. Cordero, S.S. Motsa, J.R. Torregrosa, An eighth-order family of optimal multiple root finders and its dynamics. Numer. Algor. (2017). doi: 10.1007/s11075-017-0361-6F.I. Chicharro, A. Cordero, J. R. Torregrosa, Drawing dynamical and parameters planes of iterative families and methods. Sci. World J. ID 780153 (2013)A. Constantinides, N. Mostoufi, Numerical Methods for Chemical Engineers with MATLAB Applications (Prentice Hall PTR, New Jersey, 1999)J.M. Douglas, Process Dynamics and Control, vol. 2 (Prentice Hall, Englewood Cliffs, 1972)Y.H. Geum, Y.I. Kim, B. Neta, A class of two-point sixth-order multiple-zero finders of modified double-Newton type and their dynamics. Appl. Math. Comput. 270, 387–400 (2015)Y.H. Geum, Y.I. Kim, B. Neta, A sixth-order family of three-point modified Newton-like multiple-root finders and the dynamics behind their extraneous fixed points. Appl. Math. Comput. 283, 120–140 (2016)J.L. Hueso, E. Martınez, C. Teruel, Determination of multiple roots of nonlinear equations and applications. J. Math. Chem. 53, 880–892 (2015)L.O. Jay, A note on Q-order of convergence. BIT Numer. Math. 41, 422–429 (2001)S. Li, X. Liao, L. Cheng, A new fourth-order iterative method for finding multiple roots of nonlinear equations. Appl. Math. Comput. 215, 1288–1292 (2009)S.G. Li, L.Z. Cheng, B. Neta, Some fourth-order nonlinear solvers with closed formulae for multiple roots. Comput. Math. Appl. 59, 126–135 (2010)B. Liu, X. Zhou, A new family of fourth-order methods for multiple roots of nonlinear equations. Nonlinear Anal. Model. Control 18(2), 143–152 (2013)M. Shacham, Numerical solution of constrained nonlinear algebraic equations. Int. J. Numer. Method Eng. 23, 1455–1481 (1986)M. Sharifi, D.K.R. Babajee, F. Soleymani, Finding the solution of nonlinear equations by a class of optimal methods. Comput. Math. Appl. 63, 764–774 (2012)J.R. Sharma, R. Sharma, Modified Jarratt method for computing multiple roots. Appl. Math. Comput. 217, 878–881 (2010)F. Soleymani, D.K.R. Babajee, T. Lofti, On a numerical technique forfinding multiple zeros and its dynamic. J. Egypt. Math. Soc. 21, 346–353 (2013)F. Soleymani, D.K.R. Babajee, Computing multiple zeros using a class of quartically convergent methods. Alex. Eng. J. 52, 531–541 (2013)R. Thukral, A new family of fourth-order iterative methods for solving nonlinear equations with multiple roots. J. Numer. Math. Stoch. 6(1), 37–44 (2014)R. Thukral, Introduction to higher-order iterative methods for finding multiple roots of nonlinear equations. J. Math. Article ID 404635 (2013)X. Zhou, X. Chen, Y. Song, Constructing higher-order methods for obtaining the muliplte roots of nonlinear equations. J. Comput. Math. Appl. 235, 4199–4206 (2011)X. Zhou, X. Chen, Y. Song, Families of third and fourth order methods for multiple roots of nonlinear equations. Appl. Math. Comput. 219, 6030–6038 (2013

A study of employee affective organisational commitment and retention in Pakistan:the roles of psychological contract breach and norms of reciprocity

Social exchange theory and notions of reciprocity have long been assumed to explain the relationship between psychological contract breach and important employee outcomes. To date, however, there has been no explicit testing of these assumptions. This research, therefore, explores the mediating role of negative, generalized, and balanced reciprocity, in the relationships between psychological contract breach and employees’ affective organizational commitment and turnover intentions. A survey of 247 Pakistani employees of a large public university was analyzed using structural equation modeling and bootstrapping techniques, and provided excellent support for our model. As predicted, psychological contract breach was positively related to negative reciprocity norms and negatively related to generalized and balanced reciprocity norms. Negative and generalized (but not balanced) reciprocity were negatively and positively (respectively) related to employees’ affective organizational commitment and fully mediated the relationship between psychological contract breach and affective organizational commitment. Moreover, affective organizational commitment fully mediated the relationship between generalized and negative reciprocity and employees’ turnover intentions. Implications for theory and practice are discussed

The mediating role of discrete emotions in the relationship between injustice and counterproductive work behaviors:a study in Pakistan

Purpose: Our study explores the mediating role of discrete emotions in the relationships between employee perceptions of distributive and procedural injustice, regarding an annual salary raise, and counterproductive work behaviors (CWBs). Design/Methodology/Approach: Survey data were provided by 508 individuals from telecom and IT companies in Pakistan. Confirmatory factor analysis, structural equation modeling, and bootstrapping were used to test our hypothesized model. Findings: We found a good fit between the data and our tested model. As predicted, anger (and not sadness) was positively related to aggressive CWBs (abuse against others and production deviance) and fully mediated the relationship between perceived distributive injustice and these CWBs. Against predictions, however, neither sadness nor anger was significantly related to employee withdrawal. Implications: Our findings provide organizations with an insight into the emotional consequences of unfair HR policies, and the potential implications for CWBs. Such knowledge may help employers to develop training and counseling interventions that support the effective management of emotions at work. Our findings are particularly salient for national and multinational organizations in Pakistan. Originality/Value: This is one of the first studies to provide empirical support for the relationships between in/justice, discrete emotions and CWBs in a non-Western (Pakistani) context. Our study also provides new evidence for the differential effects of outward/inward emotions on aggressive/passive CWBs

Double jeopardy:subordinates' worldviews and poor performance as predictors of abusive supervision

Purpose - To test a moderated mediation model where a positive relationship between subordinates’ perceptions of a dangerous world—the extent to which an individual views the world as a dangerous place—and supervisory abuse is mediated by their submission to authority figures, and that this relationship is heightened for more poorly performing employees. Design/Methodology/Approach - Data were obtained from 173 subordinates and 45 supervisors working in different private sector organizations in Pakistan. Findings - Our model was supported. It appears that subordinates’ dangerous worldviews are positively associated with their perceptions of abusive supervision and that this is because such views are likely to lead to greater submission to authority figures. But this is only for those employees who are performing more poorly. Implications - We highlight the possibility that individual differences (worldviews, attitudes to authority figures, and performance levels) may lead employees to become victims of abusive supervision. As such, our research informs organizations on how they may better support supervisors in managing effectively their subordinate relationships and, in particular, subordinate poor performance. Originality/Value - We add to recent work exploring subordinate-focused antecedents of abusive supervision, finding support for the salience of the previously untested constructs of individual worldviews, authoritarian submission, and individual job performance. In so doing we also extend research on dangerous worldviews into a new organizational setting. Finally, our research takes place within a new Pakistani context, adding to the burgeoning non-US based body of empirical work into the antecedents and consequences of abusive supervision

GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment

Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice