Conquering complexity : Succewsful strategies for finding disease genes in multiple sclerosis

Multiple sclerosis (MS) is a complex disease; at an intra-individual level several contributory factors cause the disease; at an inter-individual level different factors contribute to the disease. The aim of the thesis project was to reduce this complexity by focusing of subsets of patients that were likely to share to a higher extent contributory causes and to identify in these subsets genes conferring susceptibility. In paper I we wanted to know the HLA-DRB1 allele associated to the small fraction of MS patients lacking signs of immunoglobulin synthesis within the central nervous system (OCB-negative MS). In papers III and IV we performed whole-genome singlenucleotide-polymorphism (SNP) scans to identify genetic susceptibility regions in distantly related patients from an MS cluster in a parish in Värmland (paper III) and in a consanguineous family with several affected family members (paper IV). We also asked the question if differences in etiology are reflected in clinical parameters such as the severity of the disease, which we looked at in both papers I and II in relation to OCB status (I and II) and HLA-DRB1 alleles (II). Some of the main results in this thesis project and their congruence with previous reports of genetic susceptibility in MS are the following: the association between the OCB-negative entity and HLA-DRB1*04 seen both in our population and in Japan; the potential importance of the ACCN1 gene, identified in our distantly related MS patients and in an isolated population in Sardinia; the role of mutations in the PLP1 gene on the X chromosome reported in two MS case reports, thus indicating the plausibility of monogenic X-linked MS. The results derived from this thesis project merit follow-up

Does feedback and job engagement predict job satisfaction? : A comparative study between office and industrial workers

Syftet med studien var att undersöka om feedback och arbetsengagemang predicerade arbetstillfredsställelse. Syftet var även att undersöka om det förekom en skillnad i hur kontors- respektive industrianställda predicerar arbetstillfredsställelse. En kvantitativ metod användes där en enkät distribuerades ut via sociala medier. Enkäten baserades på tre redan validerade skalor, Feedback Orientation Scale (FOS), Ultrecht Work Engagement Scale (UWES) och Minnesota Satisfaction Questionnaire (MSQ). En multipel regressionsanalys genomfördes där prediktorerna yrkestillhörighet, feedback och arbetsengagemang ställdes mot arbetstillfredsställelse. Resultatet visade att arbetsengagemang signifikant predicerade arbetstillfredsställelse men att feedback inte gjorde det. Resultatet visade ingen signifikant skillnad i hur kontors- respektive industrianställda predicerade arbetstillfredsställelse. Slutsatsen var att organisationer behöver se över hur de arbetar med att engagera sina medarbetare. Hittar de rätt strategier kan det leda till en ökad arbetstillfredsställelse hos medarbetarna.The purpose of the present study was to investigate whether feedback and work engagement predicted job satisfaction. The purpose was also to investigate whether there was a difference in how office and industrial employees predict job satisfaction. A quantitative method was used where a questionnaire was distributed via social media. The survey was based on three already validated scales, the Feedback Orientation Scale (FOS), the Ultrecht Work Engagement Scale (UWES) and the Minnesota Satisfaction Questionnaire (MSQ). A multiple regression analysis was performed in which the predictors profession, feedback and work engagement were set against job satisfaction. The results showed that work engagement significantly predicted job satisfaction whereas feedback did not. The results showed no significant difference in how office and industrial employees predicted job satisfaction. The conclusion was that organizations need to review how they work with engaging their employees. Finding the right strategies can lead to increased job satisfaction among employees

Does feedback and job engagement predict job satisfaction? : A comparative study between office and industrial workers

Syftet med studien var att undersöka om feedback och arbetsengagemang predicerade arbetstillfredsställelse. Syftet var även att undersöka om det förekom en skillnad i hur kontors- respektive industrianställda predicerar arbetstillfredsställelse. En kvantitativ metod användes där en enkät distribuerades ut via sociala medier. Enkäten baserades på tre redan validerade skalor, Feedback Orientation Scale (FOS), Ultrecht Work Engagement Scale (UWES) och Minnesota Satisfaction Questionnaire (MSQ). En multipel regressionsanalys genomfördes där prediktorerna yrkestillhörighet, feedback och arbetsengagemang ställdes mot arbetstillfredsställelse. Resultatet visade att arbetsengagemang signifikant predicerade arbetstillfredsställelse men att feedback inte gjorde det. Resultatet visade ingen signifikant skillnad i hur kontors- respektive industrianställda predicerade arbetstillfredsställelse. Slutsatsen var att organisationer behöver se över hur de arbetar med att engagera sina medarbetare. Hittar de rätt strategier kan det leda till en ökad arbetstillfredsställelse hos medarbetarna.The purpose of the present study was to investigate whether feedback and work engagement predicted job satisfaction. The purpose was also to investigate whether there was a difference in how office and industrial employees predict job satisfaction. A quantitative method was used where a questionnaire was distributed via social media. The survey was based on three already validated scales, the Feedback Orientation Scale (FOS), the Ultrecht Work Engagement Scale (UWES) and the Minnesota Satisfaction Questionnaire (MSQ). A multiple regression analysis was performed in which the predictors profession, feedback and work engagement were set against job satisfaction. The results showed that work engagement significantly predicted job satisfaction whereas feedback did not. The results showed no significant difference in how office and industrial employees predicted job satisfaction. The conclusion was that organizations need to review how they work with engaging their employees. Finding the right strategies can lead to increased job satisfaction among employees

Development of interpretation keys for environmental product declarations

Certified environmental product declarations (EPD) are beginning to be used in several countries. To date, user experience indicates that the EPD results are difficult for professional purchasers and salespeople to understand. In order to improve understanding, three interpretation keys have been developed. They recalculate the EPD results to other numbers, which are easier to value. One key calculates the degree of satisfaction of environmental goals, another calculates the damage cost and yet another compares with what is normal in economic activity. The three interpretation keys represent different ethical views of the environment. Intended users, people having some knowledge of environmental issues without being specialists, have tested the keys on several occasions after which the keys were redesigned. We concluded that the interpretation keys offer increased understanding. (c) 2007 Elsevier Ltd. All rights reserved

Identity-by-descent mapping in a Scandinavian multiple sclerosis cohort

In an attempt to map chromosomal regions carrying rare gene variants contributing to the risk of multiple sclerosis (MS), we identified segments shared identical-by-descent (IBD) using the software BEAGLE 4.0’s refined IBD analysis. IBD mapping aims at identifying segments inherited from a common ancestor and shared more frequently in case–case pairs. A total of 2106 MS patients of Nordic origin and 624 matched controls were genotyped on Illumina Human Quad 660 chip and an additional 1352 ethnically matched controls typed on Illumina HumanHap 550 and Illumina 1M were added. The quality control left a total of 441 731 markers for the analysis. After identification of segments shared by descent and significance testing, a filter function for markers with low IBD sharing was applied. Four regions on chromosomes 5, 9, 14 and 19 were found to be significantly associated with the risk for MS. However, all markers but for one were located telomerically, including the very distal markers. For methodological reasons, such segments have a low sharing of IBD signals and are prone to be false positives. One marker on chromosome 19 reached genome-wide significance and was not one of the distal markers. This marker was located within the GNA11 gene, which contains no previous association with MS. We conclude that IBD mapping is not sufficiently powered to identify MS risk loci even in ethnically relatively homogenous populations, or that alternatively rare variants are not adequately present