Plasma interferon-alpha is associated with double-positivity for autoantibodies but is not a predictor of remission in early rheumatoid arthritis-a spin-off study of the NORD-STAR randomized clinical trial

BACKGROUND: The type I interferon (IFN) gene signature is present in a subgroup of patients with early rheumatoid arthritis (RA). Protein levels of IFNα have not been measured in RA and it is unknown whether they associate with clinical characteristics or treatment effect. METHODS: Patients with early untreated RA (n = 347) were randomized to methotrexate combined with prednisone, certolizumab-pegol, abatacept, or tocilizumab. Plasma IFNα protein levels were determined by single molecular array (Simoa) before and 24 weeks after treatment initiation and were related to demographic and clinical factors including clinical disease activity index, disease activity score in 28 joints, swollen and tender joint counts, and patient global assessment. RESULTS: IFNα protein positivity was found in 26% of the patients, and of these, 92% were double-positive for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). IFNα protein levels were reduced 24 weeks after treatment initiation, and the absolute change was similar irrespective of treatment. IFNα protein positivity was associated neither with disease activity nor with achievement of CDAI remission 24 weeks after randomization. CONCLUSION: IFNα protein positivity is present in a subgroup of patients with early RA and associates with double-positivity for autoantibodies but not with disease activity. Pre-treatment IFNα positivity did not predict remission in any of the treatment arms, suggesting that the IFNα system is distinct from the pathways of TNF, IL-6, and T-cell activation in early RA. A spin-off study of the NORD-STAR randomized clinical trial, NCT01491815 (ClinicalTrials), registered 12/08/2011, https://clinicaltrials.gov/ct2/show/NCT01491815

Ex-post Performance Implications of Divergence of Managers’ Perceptions of ‘Distance’ From ‘Reality’ in International Business

Despite much research on “distance”, little attention has been paid to the effect of divergence of managers’ perceptions of distance from reality (i.e. distance divergence) and its implications for firm performance. This knowledge is highly important since managerial perceptions of the firm’s environment do not always coincide with the actual environmental characteristics. Consequently, strategies based on inaccurate data may result in erroneous forecasts, missed opportunities and business failure. Using survey data from senior managers of Swedish exporters and corresponding objective data, this study is a first attempt to explore the ex-post performance implications of “distance divergence” when expanding into foreign markets. Our results demonstrate that the larger the divergence between managers’ perceptions of cultural distance and corresponding “objective” distance, the lower the performance expressed in companies’ sales. However, over/underestimation of cultural distance does not have differential effects on firm performance.“Stiftelsen Olle Hakelius Stipendiefond”, Grant no: 1165001

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants.

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling

Reducing Private Car Demand, Fact or Fiction? A Study Mapping Changes in Accessibility to Grocery Stores in Norway

BACKGROUND: Travel surveys show that the amount of private car driving in Norway has increased significantly since the mid-1980s. Private car driving has for a long time been the main mode of transport for retail and service trips, and grocery shopping trips represent over 60% of the retail and service travels. Despite the growing number of studies addressing accessibility to daily destinations, to the best of the authors’ knowledge there are no studies examining these issues over time. METHODS: This paper aims to investigate changes in accessibility to grocery stores over time and use two counties in Norway as examples. Based on GIS data at a detailed level, distances from dwellings to nearest grocery store has been examined. FINDINGS: The results from the spatial analyses reveal significant changes from 1980 to 2019: The share of the population living within 500-m from a grocery store has decreased from 55% to 34% in one of the counties examined and from 36% to 19% in the other. This indicates that the share of people living within walking distance to a local grocery store has nearly halved. With such changes in accessibility to grocery stores, increased car driving for grocery shopping should not come as a surprise. Contrary to the frequent statements about sustainable urban development and active transportation, it seems that Norway still is developing as a country that in the future will be more and not less dependent on private cars