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Moderate Effects (moderate + effects)
Selected AbstractsSimple estimates of haplotype relative risks in case-control dataGENETIC EPIDEMIOLOGY, Issue 6 2006Benjamin French Abstract Methods of varying complexity have been proposed to efficiently estimate haplotype relative risks in case-control data. Our goal was to compare methods that estimate associations between disease conditions and common haplotypes in large case-control studies such that haplotype imputation is done once as a simple data-processing step. We performed a simulation study based on haplotype frequencies for two renin-angiotensin system genes. The iterative and noniterative methods we compared involved fitting a weighted logistic regression, but differed in how the probability weights were specified. We also quantified the amount of ambiguity in the simulated genes. For one gene, there was essentially no uncertainty in the imputed diplotypes and every method performed well. For the other, ,60% of individuals had an unambiguous diplotype, and ,90% had a highest posterior probability greater than 0.75. For this gene, all methods performed well under no genetic effects, moderate effects, and strong effects tagged by a single nucleotide polymorphism (SNP). Noniterative methods produced biased estimates under strong effects not tagged by an SNP. For the most likely diplotype, median bias of the log-relative risks ranged between ,0.49 and 0.22 over all haplotypes. For all possible diplotypes, median bias ranged between ,0.73 and 0.08. Results were similar under interaction with a binary covariate. Noniterative weighted logistic regression provides valid tests for genetic associations and reliable estimates of modest effects of common haplotypes, and can be implemented in standard software. The potential for phase ambiguity does not necessarily imply uncertainty in imputed diplotypes, especially in large studies of common haplotypes. Genet. Epidemiol. 2006. © 2006 Wiley-Liss, Inc. [source] Naltrexone Selectively Elevates GABAergic Neuroactive Steroid Levels in Heavy Drinkers With the ASP40 Allele of the OPRM1 Gene: A Pilot InvestigationALCOHOLISM, Issue 8 2010Lara A. Ray Background:, Preclinical studies have implicated GABAergic neurosteroids in behavioral responses to alcohol. Naltrexone is thought to blunt the reinforcing effects of alcohol, and a few studies have found that the effects of naltrexone are moderated by the Asn40Asp polymorphisms of the OPRM1 gene. The present study seeks to integrate these lines of research by testing (i) the moderating role of the functional Asn40Asp polymorphism of the OPRM1 gene on naltrexone-induced alternations in GABAergic neurosteroid levels, namely (3,,5,)-3-hydroxypregnan-20-one (allopregnanolone, ALLO); and (ii) the combined effects of naltrexone or genotype with alcohol administration on neurosteroid levels in a sample of at-risk drinkers. Methods:, Participants were 32 (9 females) nontreatment-seeking heavy drinkers who completed a placebo-controlled laboratory study of naltrexone (50 mg/d for 3 days) and provided complete sets of serum samples for ALLO assays before and after alcohol administration under both naltrexone and placebo conditions. Results:, Naltrexone treatment raised ALLO levels among carriers of the Asp40 allele, but not homozygotes for the Asn40 allele. The Asn40Asp polymorphism did not moderate effects of naltrexone on cortisol levels. Ethanol infusion modestly reduced ALLO levels in all subjects, independent of genotype or naltrexone exposure. Conclusions:, Naltrexone increased ALLO levels among individuals with the Asn40Asp allele suggesting a potential neurosteroid contribution to the neuropharmacological effects of naltrexone among Asp40 carriers. [source] The University of California, San Francisco Family Alcoholism Study.ALCOHOLISM, Issue 10 2004Background: The University of California, San Francisco (UCSF) Family Alcoholism Study is a project designed to identify genetic loci that influence susceptibility to alcohol dependence and related phenotypes. Evidence supports a substantial genetic contribution to alcoholism susceptibility. However, the genetic epidemiology of alcoholism is complex, and its clinical manifestation is heterogeneous, making phenotype definition and demonstration of linkage difficult. Despite these challenges, some progress has been made toward identifying genes. Methods: The UCSF Family Alcoholism Study used a small family design, focusing primarily on sibling pairs and parent-child trios for linkage and association studies. Alcoholism-related phenotypes were assessed through interview and self-report questionnaires, with a focus on unidimensional and subphenotypical traits. Data-driven approaches to determining the most promising phenotypes for genetic analysis are being used. Both genome-wide scan and candidate gene approaches were used. Results: The study enrolled 2154 individuals from 970 families from December 1995 through January 2003. Test-retest and interrater reliability for clinical data are very good, and power estimates suggest that this study will have adequate power by linkage analysis to detect loci with moderate effects. Design, methods, and sample demographics of the UCSF Family Study are presented, along with intrafamilial correlations for primary diagnostic phenotypes. Conclusions: Plans for genetic analysis, novel approaches to phenotype refinement, and the implications of ascertainment bias for heritability estimates are discussed. [source] Explicitly Teaching for Transfer: Effects on the Mathematical Problem-Solving Performance of Students with Mathematics DisabilitiesLEARNING DISABILITIES RESEARCH & PRACTICE, Issue 2 2002Lynn S. Fuchs The purpose of this study was to explore methods to enhance mathematical problem solving for students with mathematics disabilities (MD). A small-group problem-solving tutoring treatment incorporated explicit instruction on problem-solution rules and on transfer. The transfer component was designed to increase awareness of the connections between novel and familiar problems by broadening the categories by which students group problems requiring the same solution methods and by prompting students to search novel problems for these broad categories. To create a stringent test of efficacy, we incorporated a computer-assisted practice condition, which provided students with direct practice on real-world problem-solving tasks. We randomly assigned 40 students to problem-solving tutoring, computer-assisted practice, problem-solving tutoring plus computer-assisted practice, or control, and pre- and posttested students on three problem-solving tasks. On story problems and transfer story problems, tutoring (with or without computer-assisted practice) effected reliably stronger growth compared to control; effects on real-world problem solving, although moderate to large, were not statistically significant. Computer-assisted practice added little value beyond tutoring but, alone, yielded moderate effects on two measures. [source] Cation-induced superoxide generation in tobacco cell suspension culture is dependent on ion valencePLANT CELL & ENVIRONMENT, Issue 11 2001T. Kawano Abstract There have been many reports suggesting the involvement of reactive oxygen species (ROS), including superoxide anion (O2.,), in salt stress. Herein, direct evidence that treatments of cell suspension culture of tobacco (Nicotiana tabacum L.; cell line, BY-2) with various salts of trivalent, divalent and monovalent metals stimulate the immediate production of O2., is reported. Among the salts tested, LaCl3 and GdCl3 induced the greatest responses in O2., production, whereas CaCl2 and MgCl2 showed only moderate effects; salts of monovalent metals such as KCl and NaCl induced much lower responses, indicating that there is a strong relationship between the valence of metals and the level of O2., production. As the valence of the added metals increased from monovalent to divalent and trivalent, the concentrations required for maximal responses were lowered. Although O2., production by NaCl and KCl required high concentrations associated with hyperosmolarity, the O2., generation induced by NaCl and KCl was significantly greater than that induced simply by hyperosmolarity. Since an NADPH oxidase inhibitor, diphenyleneiodonium chloride, showed a strong inhibitory effect on the trivalent and divalent cation-induced generation of O2.,, it is likely that cation treatments activate the O2., -generating activity of NADPH oxidase. [source] The relative contributions of the Cattell-Horn-Carroll cognitive abilities in explaining writing achievement during childhood and adolescence,PSYCHOLOGY IN THE SCHOOLS, Issue 2 2008Randy G. Floyd This study examined the relative contributions of measures of Cattell-Horn-Carroll (CHC) cognitive abilities in explaining writing achievement. Drawing from samples that covered the age range of 7 to 18 years, simultaneous multiple regression was used to regress scores from the Woodcock-Johnson III (WJ III; Woodcock, McGrew, & Mather, 2001) that represent CHC broad and narrow abilities onto the WJ III Basic Writing Skills and Written Expression cluster scores. At most age levels, Comprehension-Knowledge demonstrated moderate to strong effects on both writing clusters, Processing Speed demonstrated moderate effects on Basic Writing Skills and moderate to strong effects on Written Expression, and Short-Term Memory demonstrated moderate effects. At the youngest age levels, Long-Term Retrieval demonstrated moderate to strong effects on Basic Writing Skills and moderate effects on Written Expression. Auditory Processing, and Phonemic Awareness demonstrated moderate effects on only Written Expression at the youngest age levels and at some of the oldest age levels. Fluid Reasoning demonstrated moderate effects on both writing clusters only during some of the oldest age levels. Visual-Spatial Thinking primarily demonstrated negligible effects. The results provide insights into the cognitive abilities most important for understanding the writing skills of children during the school-age years. © 2008 Wiley Periodicals, Inc. [source] Neisseria gonorrhoeae downregulates expression of the human antimicrobial peptide LL-37CELLULAR MICROBIOLOGY, Issue 7 2005Peter Bergman Summary Neisseria gonorrhoeae is a human pathogen causing the sexually transmitted disease gonorrhoeae. The bacteria preferentially attach to and invade epithelial cells of the genital tract. As these cells previously have been shown to express the human cathelicidin LL-37, we wanted to investigate the role of LL-37 during N. gonorrhoeae infection. The cervical epithelial cell line ME180 was utilized and the expression of LL-37 was confirmed on both peptide and transcriptional levels. Moreover, LL-37 exhibited potent in vitro activity ,against ,N. ,gonorrhoeae.,Interestingly, ,the transcript and peptide levels of LL-37 were downregulated ,during ,infection, ,according ,to ,quantitative real-time polymerase chain reaction (PCR) and immunocyto-chemistry. The downregulation was most prominent with pathogenic strains of Neisseria, while non-pathogenic strains such as Neisseria lactamica and Escherichia coli only exhibited moderate effects. Heat-killed N. gonorrhoeae had no impact on the downregulation, emphasizing the importance of live bacteria. The results in this study suggest that pathogenic Neisseria may gain a survival advantage in the female genital tract by downregulating LL-37 expression. [source] Classroom and Developmental Differences in a Path Model of Teacher Expectancy EffectsCHILD DEVELOPMENT, Issue 5 2001Margaret R. Kuklinski A path model of teacher expectancy effects was evaluated in a sample of 376 first- through fifth-grade urban elementary school children. The roles of two moderators (classroom perceived differential treatment environment and developmental differences) and one mediator (children's self-expectations) of teacher expectancy effects on children's year-end achievement were examined. Significant differences in effects and effect sizes are presented. Both classroom environment (high versus low in differential treatment, as seen through children's eyes) and developmental differences moderated the strength of teacher expectancy effects. Generally, stronger effects were found in classrooms in which expectancy-related cues were more salient to children, but developmental differences moderated which effect was most pronounced. A significant age-related decline in direct effects on ending achievement was interpreted as evidence that teacher expectations may tend to magnify achievement differences in the early grades, but serve to sustain them in later grades. Support for indirect effects (teacher expectations , children's self-expectations , ending achievement) was limited to upper elementary grade classrooms perceived as high in differential treatment. In contrast to prior research that emphasized small effect sizes, the present analyses document several instances of moderate effects, primarily in classrooms in which expectancy-related messages were most salient to children. These results underscore the importance of explicit attention to the inclusion of moderators, mediators, and multiple outcomes in efforts to understand teacher expectancy effects. [source] | |||||||||||||