Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery datasets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5×10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signaling and cytokine-cytokine pathways, for which relevant therapies exist.

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The first substantial comparison between rings and rain wi.th which th~ author is acquainted was made by the astronomer, J. C. Kapteyn of Holland, in 188o and r881 on oaks in the Rhine region. P rofessor Kapteyn has recently prepared and published a brief pamphlet on the subject. 2 A similar comparison between the growth of the great sequoia (Sequoia gigantea), and rainfall is shown in figure I in which the curve for rainfall is from Huntington, 3 from data at Fresno, 70 miles away and 5,000 feet lower in elevation. In s.pite of widely different conditions there is evident reseml'eor.s FrG. r. Comparison • of rainfall at Fresno, Calif.ornia, and growth of sequoias. (Rainfall af•ter Huntington.

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Illness scripts are knowledge structures composed of consequences, enabling conditions, and faults. The effects of illness script components--consequences and enabling conditions--and physician factors on referral decisions for gastrointestinal disorders were investigated. The hypothesis that consequences and enabling conditions increase the likelihood of referral was confirmed and several interactions between consequences and enabling conditions were found. The hypothesis that physician factors moderate the effect of enabling conditions was also confirmed, but (contrary to illness script theory) evidence was also found for moderation of consequences. Both enabling conditions and consequences were found to be moderated by physician factors to a larger extent than previously assumed by illness script theory.

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Within the framework of technology acceptance modelling (Davis 1993), this study investigated the acceptance of a computerised decision-support system in primary care. Thirty general practitioners (GP) completed a questionnaire that detailed potential advantages of the system. A majority (70%) of GPs intended to use the system with a 2-min increase in consultation times (for proportion of GPs intending to use, CI 0.95 = [0.54; 0.85]) and eight advantages of the system were predictors of intention to use (R L 2 = 0.51, p 5 0.05). However, a majority (77%) did not intend to use the system with a 5-min increase in consultation time (CI 0.95 = [0.12; 0.42]). Furthermore, a majority of 90% preferred the system to be used by non-physicians (CI 0.95 = [0.78; 0.98]). These results confirm relationships between acceptance factors in a new domain, but most importantly they indicate the need to consider the balance of perceived advantages, or benefits, and disadvantages, or costs, of a new system in technology acceptance modelling. Implications for the design of a prototype system and further research are discussed.