Linkage analysis of candidate genes in autoimmune thyroid disease: 1. Selected immunoregulatory genes. International Consortium for the Genetics of Autoimmune Thyroid Disease

Graves' and Hashimoto's diseases are autoimmune thyroid diseases in which the genetic contribution is complex. For this reason, identification of necessary susceptibility genes has been difficult. However, a number of immunoregulatory genes have been implicated by association studies, including: CTLA-4, a recently described protein involved in antigen presentation, located on chromosome 2q33; the T-cell receptor V alpha and V beta gene complexes, located on 14q11 and 7q35, respectively; and the Ig gene complex (IgH), located on 15q11. We used polymorphic microsatellite markers located within these genes, or gene complexes, to test for linkage (rather than association), to each of these candidates. Using markers within the loci allowed us to assume a fixed recombination fraction of 0.01 in the tested model. Three hundred eight subjects from 48 multiplex families were studied, with 142 affected subjects. Using this set of families, we have previously shown evidence of linkage with a major susceptibility locus for Graves' disease (GD-1) on 14q24.3-31, with a maximum lod (logarithm + odds) score of 2.1, at a penetrance of 80% and with a dominant mode of inheritance. In the present study, we obtained consistently negative lod scores for each of the candidate genes, assuming either dominant or recessive modes of inheritance. These data, therefore, showed evidence against linkage with all the candidate genes. Unlike association studies, linkage analyses detect major genetic influences on disease susceptibility exerted by the linked loci. The lack of linkage for the immunoregulatory genes that were studied indicated, therefore, that they were not major contributors to disease etiology.     

The geographic variation of cancer incidence in Ontario

OBJECTIVES: Our objectives were (1) to describe an analysis of the spatial pattern of cancer incidence in Ontario and (2) to discuss the quality of data in the Ontario Cancer Registry with respect to the accuracy of local cancer rates. METHODS: Cancer incidence rates were calculated for 22 cancer sites in 49 counties of Ontario during 1976 to 1986. Capture-recapture methods were used to estimate completeness of case registration, and completeness of residence information was also assessed. Spatial autocorrelation was used in measuring the geographic pattern of incidence rates. Comparisons were also made between sexes and with earlier data from 1966 to 1975. RESULTS: The quality of the geographic data in the registry appeared good, and corrections for incomplete or inaccurate registration had little impact. About one third of the sex-site combinations showed some evidence of spatial patterning in the cancer rate. Particularly strong regional variation was noted for cancers of the stomach, lung, uterus, and prostate. CONCLUSIONS: The analysis revealed a number of cancers with significant spatial patterning of risk. Further work is needed to relate the cancer data to other information on potential life-style and environmental factors.     

Evidence-Based Solutions for Overcoming Access Barriers, Decreasing Attrition, and Promoting Change With Underserved Families.

Various definitions exist for what constitutes family therapy. In this article, we consider family therapy to encompass any intervention that targets family interactions and conceptualizes problems as existing beyond individual clients. Numerous individual studies and several quantitative reviews have established family therapy as an effective treatment modality and the treatment of choice for many disorders. However, critiques of existing service provision highlight the unfortunate fact that numerous barriers to treatment exist at multiple levels of the broader ecology, preventing many families from benefiting from these services. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Kinetics of the inhibition of ascorbic acid browning by sulphite.

Despite differences in the structures of aldoses and ascorbic acid, ASA, the non-enzymic browning of the latter involves intermediates similar to those found in Maillard browning. The kinetics of the sulphite-inhibited browning of ASA suggest that, under anaerobic conditions, the rate of reaction of sulphite species, S(IV), is of first order with respect to S(IV). The possibility that S(IV) could catalyse the hydrolysis of the lactone ring of ASA is considered by reference to D-glucono-delta-lactone. Evidence is presented to suggest that, under aerobic conditions, autoxidation of ASA leads to the oxidation of S(IV). The composition of melanoidins from ASA-glycine mixtures is compared with that from arabinose-glycine; the former contain 2 x 5 times more ASA-derived residues per glycine molecule than arabinose-derived residues per glycine molecule in the latter. The implications of these findings to the mechanism of ASA browning are discussed.     

A Fifth Order Flux Implicit WENO Method

The weighted essentially non-oscillatory (WENO) method is an excellent spatial discretization for hyperbolic partial differential equations with discontinuous solutions. However, the time-step restriction associated with explicit methods may pose severe limitations on their use in applications requiring large scale computations. An efficient implicit WENO method is necessary. In this paper, we propose a prototype flux-implicit WENO (iWENO) method. Numerical tests on classical scalar equations show that this is a viable and stable method, which requires appropriate time-stepping methods. Future study will include the examination of such methods as well as extension of iWENO to systems and higher dimensional problems.Sigal Gottlieb - The work of this author supported by NSF grant DMS-0106743.Steven J. Ruuth - The work of this author was partially supported by a grant from NSERC Canada.     

Binding, relational memory, and recall of naturalistic events: A developmental perspective.

This research was an investigation of children's performance on a task that requires memory binding. In Experiments 1 and 2, 4-year-olds, 6-year-olds, and adults viewed complex pictures and were tested on memory for isolated parts in the pictures and on the part combinations (combination condition). The results suggested improvement in memory for the combinations between the ages of 4 and 6 years but not in memory for the isolated parts. In Experiments 2 and 3, the authors also examined the developmental relationship between performance in the combination condition and free recall of a naturalistic event, finding preliminary evidence that performance on a memory task that requires binding is positively related to performance in episodic memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Writing quality, reading skills, and domain knowledge as factors in text comprehension.

103 undergraduates listened to and recalled 3 passages and were given a general reading comprehension test. The passages were presented such that Ss could use general knowledge to understand them or such that no specific world knowledge seemed applicable. The passages were written in 2 different versions, preserving their content but varying their style. All 3 factors (domain knowledge, writing style, and skill) significantly affected reproductive recall, and there were no interactions between these factors. However, while good writing was sufficient to improve the reproduction of the texts, an analysis of the recall elaborations Ss made revealed that the correctness of their elaborations depended strongly on the availability of appropriate domain knowledge. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)