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Objectives:Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases, comprising seven categories. Genetic data could potentially be used to help redefine JIA categories and improve the current classification system. The human leukocyte antigen (HLA) region is strongly associated with JIA. Fine-mapping of the region was performed to look for similarities and differences in HLA associations between the JIA categories and define correspondences with adult inflammatory arthritides. Methods:Dense genotype data from the HLA region, from the Immunochip array for 5,043 JIA cases and 14,390 controls, was used to impute SNPs, HLA classical alleles and amino acids. Bivariate analysis was performed to investigate genetic correlation between the JIA categories. Conditional analysis was used to identify additional effects within the region. Comparison of the findings with those in adult inflammatory arthritic diseases was performed.ResultsWe identified category-specific associations and have demonstrated for the first time that rheumatoid factor negative polyarticular JIA and oligoarticular JIA are genetically similar in their HLA associations. We also observe that each JIA category potentially has an adult counterpart. The RF-positive polyarthritis association at HLA-DRB1 amino acid at position 13 mirrors the association in adult seropositive rheumatoid arthritis (RA). Interestingly, the combined oligoarthritis and RF-negative polyarthritis dataset shares the same association with adult seronegative RA. ConclusionsThe findings suggest the value of using genetic data in helping to classify the categories of this heterogeneous disease. Mapping JIA categories to adult counterparts could enable shared knowledge of disease pathogenesis and etiology and facilitate transition from paediatric to adult services.

Objectives Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases, comprising seven categories. Genetic data could potentially be used to help redefine JIA categories and improve the current classification system. The human leucocyte antigen (HLA) region is strongly associated with JIA. Fine-mapping of the region was performed to look for similarities and differences in HLA associations between the JIA categories and define correspondences with adult inflammatory arthritides. Methods Dense genotype data from the HLA region, from the Immunochip array for 5043 JIA cases and 14 390 controls, were used to impute single-nucleotide polymorphisms, HLA classical alleles and amino acids. Bivariate analysis was performed to investigate genetic correlation between the JIA categories. Conditional analysis was used to identify additional effects within the region. Comparison of the findings with those in adult inflammatory arthritic diseases was performed. Results We identified category-specific associations and have demonstrated for the first time that rheumatoid factor (RF)-negative polyarticular JIA and oligoarticular JIA are genetically similar in their HLA associations. We also observe that each JIA category potentially has an adult counterpart. The RF-positive polyarthritis association at HLA-DRB1 amino acid at position 13 mirrors the association in adult seropositive rheumatoid arthritis (RA). Interestingly, the combined oligoarthritis and RF-negative polyarthritis dataset shares the same association with adult seronegative RA. Conclusions The findings suggest the value of using genetic data in helping to classify the categories of this heterogeneous disease. Mapping JIA categories to adult counterparts could enable shared knowledge of disease pathogenesis and aetiology and facilitate transition from paediatric to adult services. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

Increased cholangiocyte growth is critical for the maintenance of biliary mass during liver injury by bile duct ligation (BDL). Circulating levels of testosterone decline following castration and during cholestasis. Cholangiocytes secrete sex hormones sustaining cholangiocyte growth by autocrine mechanisms. We tested the hypothesis that testosterone is an autocrine trophic factor stimulating biliary growth. The expression of androgen receptor (AR) was determined in liver sections, male cholangiocytes, and cholangiocyte cultures [normal rat intrahepatic cholangiocyte cultures (NRICC)]. Normal or BDL (immediately after surgery) rats were treated with testosterone or antitestosterone antibody or underwent surgical castration (followed by administration of testosterone) for 1 wk. We evaluated testosterone serum levels; intrahepatic bile duct mass (IBDM) in liver sections of female and male rats following the administration of testosterone; and secretin-stimulated cAMP levels and bile secretion. We evaluated the expression of 17β-hydroxysteroid dehydrogenase 3 (17β-HSD3, the enzyme regulating testosterone synthesis) in cholangiocytes. We evaluated the effect of testosterone on the proliferation of NRICC in the absence/presence of flutamide (AR antagonist) and antitestosterone antibody and the expression of 17β-HSD3. Proliferation of NRICC was evaluated following stable knock down of 17β-HSD3. We found that cholangiocytes and NRICC expressed AR. Testosterone serum levels decreased in castrated rats (prevented by the administration of testosterone) and rats receiving antitestosterone antibody. Castration decreased IBDM and secretin-stimulated cAMP levels and ductal secretion of BDL rats. Testosterone increased 17β-HSD3 expression and proliferation in NRICC that was blocked by flutamide and antitestosterone antibody. Knock down of 17β-HSD3 blocks the proliferation of NRICC. Drug targeting of 17β-HSD3 may be important for managing cholangiopathies.

Consumer neuroscience addresses marketing relevant problems through the integration and application of neuroscientific theories, concepts, findings and methods to the research discipline of consumer behavior. The key contribution of this paper is to complement the advancement of traditional consumer research through the investigation of the patterns of interdependency between the Electroencephalogram (EEG) signals from the different brain regions while participants undertook a choice task designed to elicit preferences for a marketing product (crackers). Specifically, the task required participants to choose their preferred crackers described by shape (square, triangle, round), flavor (wheat, dark rye, plain) and topping (salt, poppy, no topping).We analyze the Electroencephalogram (EEG) signals collected from the different brain regions using the commercially available 14 channel Emotiv EPOC wireless EEG headset and relate the EEG data to the specific choice options with a Tobii X60 eye tracker. Fifteen participants were recruited for this experiment and were shown 57 choice sets; each choice set described three choice options. The patterns of cortical activity were obtained in the five principal frequency bands, Delta (0 - 4 Hz), Theta (3 - 7 Hz), Alpha (8 - 12 Hz), Beta (13 - 30 Hz), and Gamma (30 - 40 Hz). Our results indicate significant phase synchronization between the left and right frontal and occipital regions indicating interhemispheric communications during the choice task. Our experimental results also show that participants spent more time looking at the non-preferred items in each choice set at the beginning of the experiment (exploration mode), while reducing that time progressively to indicate significant amount of cognitive processing assigned to preferred items (exploitation mode).

University of Technology, Sydney. Faculty of Business. NO FULL TEXT AVAILABLE. Access is restricted indefinitely. The hardcopy may be available for consultation at the UTS Library. NO FULL TEXT AVAILABLE. Access is restricted indefinitely. ----- It is critical for firms to understand how demand for their products is impacted by the way in which product information is communicated. Despite research devoted to understanding how the provision of information impacts product evaluation and choice, research on the communication of product specifications is limited. Firms often use esoteric specifications to describe attributes. In contrast to conventional specifications that are familiar and relatively easy to evaluate, esoteric specifications are defined as descriptions of product attributes that are unfamiliar, novel, and difficult to evaluate even when comparable alternatives are available to act as reference points. For example, the ‘zoom’ attribute of a digital camera may be described in a simple, easy-to-evaluate specification (e.g. 7x), or equivalently described in an esoteric, difficult-to-evaluate way (e.g. 37-260mm). Although the use of esoteric specifications is widespread, little is known about how esoteric specifications impact upon choice. Previous research suggests conflicting impacts of the use of esoteric specifications in influencing product evaluations. For instance, ambiguous attributes have been demonstrated to positively influence product evaluations, but, paradoxically, consumers often ignore product information that is difficult to evaluate, instead utilising specifications that can be easily compared across alternatives. Given these conflicting views, the objective of this thesis is to understand how esoteric specifications impact reliance on both esoterically and conventionally described attributes in choice contexts. Two discrete choice experiments examine the effects of esoteric specifications in choice in the context of digital camera and credit card choice. We demonstrate that attribute reliance in choice is lower when described by esoteric specifications than when described by conventional specifications and, as a result, reliance shifts to those other attributes conventionally described. We propose that the shift in reliance to other conventionally specified attributes depends on brand credibility. Finally, we demonstrate the moderating role of processing effort in attenuating the discounting of esoterically described attributes in choice. This thesis contributes to research on the provision of marketing information in three key ways. First, we identify esoteric specifications as an information-provision variable that has a systematic influence on evaluation and choice. Second, we provide an addition to the metacognition and ease-of-processing literature by examining the effects of processing difficulty in a choice context. Finally, this thesis contributes to the information-processing literature by demonstrating the influence of motivated processing in overcoming effects of esoteric specifications in choice. Practically, the findings suggest that firms should be mindful of the language used to describe key attributes and, in particular, whether consumers can comprehend and compare the values of stated specifications. Failure of firms to do so may lead to consumers using attribute information in choice contexts in unanticipated ways.