Prophets vs. profits: How market competition influences leaders' disciplining behavior towards ethical transgressions

We investigate how market competition influences the way organizational leaders discipline moral transgressions of employees. In a cross-sectional study among organizational leaders at various hierarchical levels (Study 1), we find that strong market competition is related to an instrumental decision frame (business practices being perceived as focused on serving the organization’s interest). This decision frame explains why strong market competition is related to leaders’ perceptions of the evaluation of wrongdoing in terms of instrumental rather than moral concerns. In two subsequent experiments (Study 2 and 3), we find that high (relative to low) market competition makes leaders’ disciplining of moral transgressions contingent upon the instrumentality of the transgression to the organization. We find that the same transgression is punished less severely when it resulted in profit for the organization than when it resulted in loss. This research is among the first to identify conditions that determine the disciplinary responses of organization leaders to employees’ moral transgressions, and it feeds the debate on whether market competition - a fundamental characteristic of capitalist economies - promotes the display of moral or immoral behavior within organization

Genome-wide association meta-analysis of functional outcome after ischemic stroke

Altres ajuts: The Stroke Genetics Network (SiGN) study was funded by a cooperative agreement grant from the US National Institute of Neurological Disorders and Stroke (NINDS), NIH (U01 NS069208 and R01 NS100178). SAHLSIS was supported by the Swedish Heart and Lung Foundation (HLF-20160316), the Swedish Research Council (K2014-64X-14605-12-5), the Swedish Stroke Association, the Swedish state (under the "Avtal om Läkarutbildning och Medicinsk Forskning, ALF") (ALFGBG-720081). Australian Stroke Genetics Collaboration study was supported by the National Health and Medical Research Council, Australia. Stroke Pharmacogenomics and Genetics group was supported by Invictus plus network, Generation project, and Miguel Servet programme from Instituto de Salud Carlos III, GODs project and Epigenesis project from Marató de TV3 Foundation and Agaur from Generalitat de Catalunya Government. Arne Lindgren was supported by the Swedish Heart and Lung Foundation, Region Skåne, Skåne University Hospital, the Freemasons Lodge of Instruction EOS in Lund, Lund University, the Foundation of Färs & Frosta-one of Spar-banken Skåne's ownership Foundations, and the Swedish Stroke Association. Martin Söderholm was supported by grants from the Swedish Stroke Association, the Foundation of Färs & Frosta-one of Sparbanken Skåne's ownership Foundations, and the Swedish government (under the "Avtal om Läkarutbildning och Medicinsk Forskning, ALF"). Annie Pedersen was supported by grants from the Swedish government (under the "Avtal om Läkarutbildning och Medi-cinsk Forskning, ALF") and the Gothenburg Foundation for Neurological Research. Natalia Rost was in part supported by NIH-NINDS (R01NS086905 and R01NS082285). Daniel Strbian was supported by the Finnish Subsidiary Governmental Fund (VTR). The authors thank NINDS for funding the genotyping of patients included in the SiGN study (U01 NS069208 and R01 NS100178) and Sólveig Grétarsdóttir for genotyping a subsample of the SAHLSIS cohort.ObjectiveTo discover common genetic variants associated with poststroke outcomes using a genome-wide association (GWA) study.MethodsThe study comprised 6,165 patients with ischemic stroke from 12 studies in Europe, the United States, and Australia included in the GISCOME (Genetics of Ischaemic Stroke Functional Outcome) network. The primary outcome was modified Rankin Scale score after 60 to 190 days, evaluated as 2 dichotomous variables (0-2 vs 3-6 and 0-1 vs 2-6) and subsequently as an ordinal variable. GWA analyses were performed in each study independently and results were meta-analyzed. Analyses were adjusted for age, sex, stroke severity (baseline NIH Stroke Scale score), and ancestry. The significance level was p < 5 × 10.ResultsWe identified one genetic variant associated with functional outcome with genome-wide significance (modified Rankin Scale scores 0-2 vs 3-6, p = 5.3 × 10). This intronic variant (rs1842681) in the LOC105372028 gene is a previously reported trans-Expression quantitative trait locus for PPP1R21, which encodes a regulatory subunit of protein phosphatase 1. This ubiquitous phosphatase is implicated in brain functions such as brain plasticity. Several variants detected in this study demonstrated suggestive association with outcome (p < 10), some of which are within or near genes with experimental evidence of influence on ischemic stroke volume and/or brain recovery (e.g., NTN4, TEK, and PTCH1).ConclusionsIn this large GWA study on functional outcome after ischemic stroke, we report one significant variant and several variants with suggestive association to outcome 3 months after stroke onset with plausible mechanistic links to poststroke recovery. Future replication studies and exploration of potential functional mechanisms for identified genetic variants are warranted

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.Paroxysmal Cerebral Disorder