Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Covariates

  • baseline covariate
  • binary covariate
  • clinical covariate
  • continuous covariate
  • demographic covariate
  • environmental covariate
  • important covariate
  • individual covariate
  • other covariate
  • potential covariate
  • relevant covariate
  • several covariate
  • significant covariate
  • time-dependent covariate
  • time-varying covariate

  • Terms modified by Covariates

  • covariate adjustment
  • covariate analysis
  • covariate data
  • covariate distribution
  • covariate effects
  • covariate information
  • covariate value

  • Selected Abstracts

    Regression Analysis with a Misclassified Covariate from a Current Status Observation Scheme

    BIOMETRICS, Issue 2 2010
    Leilei Zeng
    Summary Naive use of misclassified covariates leads to inconsistent estimators of covariate effects in regression models. A variety of methods have been proposed to address this problem including likelihood, pseudo-likelihood, estimating equation methods, and Bayesian methods, with all of these methods typically requiring either internal or external validation samples or replication studies. We consider a problem arising from a series of orthopedic studies in which interest lies in examining the effect of a short-term serological response and other covariates on the risk of developing a longer term thrombotic condition called deep vein thrombosis. The serological response is an indicator of whether the patient developed antibodies following exposure to an antithrombotic drug, but the seroconversion status of patients is only available at the time of a blood sample taken upon the discharge from hospital. The seroconversion time is therefore subject to a current status observation scheme, or Case I interval censoring, and subjects tested before seroconversion are misclassified as nonseroconverters. We develop a likelihood-based approach for fitting regression models that accounts for misclassification of the seroconversion status due to early testing using parametric and nonparametric estimates of the seroconversion time distribution. The method is shown to reduce the bias resulting from naive analyses in simulation studies and an application to the data from the orthopedic studies provides further illustration. [source]

    Covariate Adjusted Correlation Analysis with Application to,FMR1,Premutation Female Carrier Data

    BIOMETRICS, Issue 3 2009
    Damla, entürk
    Summary Motivated by molecular data on female premutation carriers of the fragile X mental retardation 1 (FMR1) gene, we present a new method of covariate adjusted correlation analysis to examine the association of messenger RNA (mRNA) and number of CGG repeat expansion in the,FMR1,gene. The association between the molecular variables in female carriers needs to adjust for activation ratio (ActRatio), a measure which accounts for the protective effects of one normal X chromosome in females carriers. However, there are inherent uncertainties in the exact effects of ActRatio on the molecular measures of interest. To account for these uncertainties, we develop a flexible adjustment that accommodates both additive and multiplicative effects of ActRatio nonparametrically. The proposed adjusted correlation uses local conditional correlations, which are local method of moments estimators, to estimate the Pearson correlation between two variables adjusted for a third observable covariate. The local method of moments estimators are averaged to arrive at the final covariate adjusted correlation estimator, which is shown to be consistent. We also develop a test to check the nonparametric joint additive and multiplicative adjustment form. Simulation studies illustrate the efficacy of the proposed method. (Application to,FMR1,premutation data on 165 female carriers indicates that the association between mRNA and CGG repeat after adjusting for ActRatio is stronger.) Finally, the results provide independent support for a specific jointly additive and multiplicative adjustment form for ActRatio previously proposed in the literature. [source]

    Interspecific Effects of Artifically Propagated Fish: an Additional Conservation Risk for Salmon

    Phillip S. Levin
    We tested the hypothesis that hatchery-reared steelhead salmon ( Oncorhynchus mykiss) released into the Snake River Basin negatively affect the survival of wild Snake River steelhead and chinook ( O. tshawytscha) salmon. Because climatic conditions can influence salmon survival, we included an index of the El Niño,Southern Oscillation ( ENSO) as a covariate in our analyses. Based on time series of hatchery releases and rates of smolt-to-adult survival, we demonstrate that the survival of wild chinook salmon is negatively associated with hatchery releases of steelhead. The state of the ( ENSO) did not affect the strength of this relationship. We observed no relationship between survival of wild steelhead and steelhead hatchery releases. Our results suggest that industrial-scale production of hatchery fish may hinder the recovery of some threatened salmonids and that the potential interspecific impact of hatcheries must be considered as agencies begin the process of hatchery reform. Resumen: Por más de 120 años, las granjas han liberado números enormes de salmones del Pacífico para compensar las numerosas agresiones humanos a sus poblaciones, sin embargo, los impactos ecológicos de este esfuerzo masivo son poco entendidos. Evaluamos la hipótesis de que la trucha cabeza de acero ( Oncorhynchus mykiss) criada en granjas y liberada en la cuenca del Río Snake afecta negativamente la supervivencia de truchas cabeza de acero y salmones chinook ( O. tshawytscha) silvestres. Puesto que las condiciones climáticas pueden influir sobre la supervivencia del salmón, incluimos un índice de la Oscilación del Niño del Sur como covariable del análisis. En base a series de tiempo de las liberaciones de las granjas y las tasas de supervivencia hasta adulto de peces migrantes al mar, demostramos que la supervivencia del salmón chinook silvestre está negativamente correlacionada con las liberaciones de truchas cabeza de acero de las granjas. El estado de la Oscilación del Niño del Sur no afectó el grado de correlación. No observamos relación alguna entre la supervivencia de las truchas silvestres y las liberaciones de las granjas. Nuestros resultados sugieren que la producción a escala industrial de peces de granja puede obstaculizar la recuperación de algunos salmónidos amenazados y que el impacto interespecífico potencial de las granjas debería ser considerado en cuanto las agencias inicien el proceso de reforma de las granjas. [source]

    On the relationship between dynamic visual and auditory processing and literacy skills; results from a large primary-school study

    DYSLEXIA, Issue 4 2002
    Joel B. Talcott
    Abstract Three hundred and fifty randomly selected primary school children completed a psychometric and psychophysical test battery to ascertain relationships between reading ability and sensitivity to dynamic visual and auditory stimuli. The first analysis examined whether sensitivity to visual coherent motion and auditory frequency resolution differed between groups of children with different literacy and cognitive skills. For both tasks, a main effect of literacy group was found in the absence of a main effect for intelligence or an interaction between these factors. To assess the potential confounding effects of attention, a second analysis of the frequency discrimination data was conducted with performance on catch trials entered as a covariate. Significant effects for both the covariate and literacy skill was found, but again there was no main effect of intelligence, nor was there an interaction between intelligence and literacy skill. Regression analyses were conducted to determine the magnitude of the relationship between sensory and literacy skills in the entire sample. Both visual motion sensitivity and auditory sensitivity to frequency differences were robust predictors of children's literacy skills and their orthographic and phonological skills. Copyright © 2002 John Wiley & Sons, Ltd. [source]

    Alcohol control policies and alcohol consumption by youth: a multi-national study

    ADDICTION, Issue 11 2009
    Mallie J. Paschall
    ABSTRACT Aims The study examined relationships between alcohol control policies and adolescent alcohol use in 26 countries. Design Cross-sectional analyses of alcohol policy ratings based on the Alcohol Policy Index (API), per capita consumption and national adolescent survey data. Setting Data are from 26 countries. Participants Adolescents (aged 15,17 years) who participated in the 2003 European School Survey Project on Alcohol and Other Drugs (ESPAD) or national secondary school surveys in Spain, Canada, Australia, New Zealand and the United States. Measurements Alcohol control policy ratings based on the API; prevalence of alcohol use, heavy drinking and first drink by age 13 based on national secondary school surveys; per capita alcohol consumption for each country in 2003. Analysis Correlational and linear regression analyses were conducted to examine relationships between alcohol control policy ratings and past 30-day prevalence of adolescent alcohol use, heavy drinking and having first drink by age 13. Per capita consumption of alcohol was included as a covariate in regression analyses. Findings More comprehensive API ratings and alcohol availability and advertising control ratings were related inversely to the past 30-day prevalence of alcohol use and prevalence rates for drinking three to five times and six or more times in the past 30 days. Alcohol advertising control was also related inversely to the prevalence of past 30-day heavy drinking and having first drink by age 13. Most of the relationships between API, alcohol availability and advertising control and drinking prevalence rates were attenuated and no longer statistically significant when controlling for per capita consumption in regression analyses, suggesting that alcohol use in the general population may confound or mediate observed relationships between alcohol control policies and youth alcohol consumption. Several of the inverse relationships remained statistically significant when controlling for per capita consumption. Conclusions More comprehensive and stringent alcohol control policies, particularly policies affecting alcohol availability and marketing, are associated with lower prevalence and frequency of adolescent alcohol consumption and age of first alcohol use. [source]

    Statistical analysis of temperature impact on daily hospital admissions: analysis of data from Udine, Italy

    ENVIRONMETRICS, Issue 1 2006
    Francesco Pauli
    Abstract This article is devoted to the analysis of the relationship between the health status of an urban population and meteorological variables. The analysis considers daily number of hospital admissions, not due to surgery, regarding the population resident in the Municipality of Udine, aged 75 and over. Hourly records on temperature, humidity, rain, atmospheric pressure, solar radiation, wind velocity and direction recorded at an observation site located near the center of Udine are considered. The study also considers hourly measures of pollutant concentrations collected by six monitoring stations. All data are relative to the summer periods of years 1995,2003. Generalized additive models (GAM) are used in which the response variable is the number of hospital admissions and is assumed to be distributed as a Poisson whose rate varies as a possibly non-linear function of the meteorological variables and variables allowing for calendar effects and pollutant concentrations. The subsequent part of the analysis explores the distribution of temperature conditional on the number of daily admissions through quantile regression. A non-linear (N-shaped) relationship between hospital admissions and temperature is estimated; temperature at 07:00 is selected as a covariate, revealing that nighttime temperature is more relevant than daytime. The quantile regression analysis points out, as expected, that the distribution of temperature on days with more admissions has higher q -quantiles with q near unity, while a clear-cut conclusion is not reached for q quantiles with q near 0. Copyright © 2005 John Wiley & Sons, Ltd. [source]

    GENETIC STUDY: H2 haplotype at chromosome 17q21.31 protects against childhood sexual abuse-associated risk for alcohol consumption and dependence

    ADDICTION BIOLOGY, Issue 1 2010
    Elliot C. Nelson
    ABSTRACT Animal research supports a central role for corticotropin-releasing factor (CRF) in actions of ethanol on brain function. An examination of alcohol consumption in adolescents reported a significant genotype × environment (G × E) interaction involving rs1876831, a corticotropin-releasing hormone receptor 1 (CRHR1) polymorphism, and negative events. CRHR1 and at least four other genes are located at 17q21.31 in an extremely large block of high linkage disequilibrium resulting from a local chromosomal inversion; the minor allele of rs1876831 is contained within the H2 haplotype. Here, we examine whether G × E interactions involving this haplotype and childhood sexual abuse (CSA) are associated with risk for alcohol consumption and dependence in Australian participants (n = 1128 respondents from 476 families) of the Nicotine Addiction Genetics project. Telephone interviews provided data on DSM-IV alcohol dependence diagnosis and CSA and enabled calculation of lifetime alcohol consumption factor score (ACFS) from four indices of alcohol consumption. Individuals reporting a history of CSA had significantly higher ACFS and increased risk for alcohol dependence. A significant G × E interaction was found for ACFS involving the H2 haplotype and CSA (P < 0.017). A similar G × E interaction was associated with protective effects against alcohol dependence risk (odds ratio 0.42; 95% confidence interval 0.20,0.89). For each outcome, no significant CSA-associated risk was observed in H2 haplotype carriers. These findings support conducting further investigation of the H2 haplotype to determine the gene(s) responsible. Our results also suggest that severe early trauma may prove to be an important clinical covariate in the treatment of alcohol dependence. [source]

    The Fear of Dental Pain questionnaire: construction and validity

    Arjen J. Van Wijk
    Anxiety, fear and pain play an important role in the context of dental treatment and patients' well-being. The Fear of Pain Questionnaire (FPQ)-III is a recently developed self-report questionnaire measuring pain-related fear of a variety of painful stimuli. The present study was undertaken in order to develop a dental equivalent of the FPQ-III, called the Fear of Dental Pain questionnaire (FDP), to determine standard psychometric characteristics and to assess the instruments' validity. Four experienced dentists generated the initial pool of items and two methodologists constructed the initial questionnaire. Two studies were performed. In the study one, a sample of psychology freshmen (n = 309) was taken in order to analyse response patterns. In study two, a sample (n = 176) of patients, dental students and the general population was examined. Results from both studies were used to determine reliability and validity. High internal consistency (0.93) with satisfactory test,retest reliability (0.75) was obtained. Factor analysis revealed a strong one-dimensional factor underlying almost all items. Finally, the proposed FDP version was related to a measure of dental fear and a general measure of fear of pain. All a priori hypotheses were confirmed, thereby providing evidence for the validity of the FDP. The FPD may prove to be a clinically useful tool in the dental setting, and a potentially important covariate in dental pain perception research. [source]

    Calibration model of microbial biomass carbon and nitrogen concentrations in soils using ultraviolet absorbance and soil organic matter

    X. Xu
    Summary There is a need for a rapid, simple and reliable method of determining soil microbial biomass (SMB) for all soils because traditional methods are laborious. Earlier studies have reported that SMB-C and -N concentrations in grassland and arable soils can be estimated by measurement of UV absorbance in soil extracts. However, these previous studies focused on soils with small soil organic matter (SOM) contents, and there was no consideration of SOM content as a covariate to improve the estimation. In this study, using tropical and temperate forest soils with a wide range of total C (5,204 mg C g,1 soil) and N (1,12 mg N g,1 soil) contents and pH values (4.1,5.9), it was found that increase in UV absorbance of soil extracts at 280 nm (UV280) after fumigation could account for 92,96% of the variance in estimates of the SMB-C and -N concentrations measured by chloroform fumigation and extraction (P < 0.001). The data were combined with those of earlier workers to calibrate UV-based regression models for all the soils, by taking into account their varying SOM content. The validation analysis of the calibration models indicated that the SMB-C and -N concentrations in the 0,5 cm forest soils simulated by using the increase in UV280 and SOM could account for 86,93% of the variance in concentrations determined by chloroform fumigation and extraction (P < 0.001). The slope values of linear regression equations between measured and simulated values were 0.94 ± 0.03 and 0.94 ± 0.04, respectively, for the SMB-C and -N. However, simulation using the regression equations obtained by using only the data for forest profile soils gave less good agreement with measured values. Hence, the calibration models obtained by using the increase in UV280 and SOM can give a rapid, simple and reliable method of determining SMB for all soils. [source]

    Assessing macroinvertebrate metrics for classifying acidified rivers across northern Europe

    FRESHWATER BIOLOGY, Issue 7 2010
    Summary 1. The effects of acidification on ecological status of rivers in Northern Europe must be assessed according to the EU Water Framework Directive (WFD). Several acidification metrics based on macroinvertebrates already exist in different countries, and the WFD requires that they be comparable across northern Europe. Thus, we compiled macroinvertebrate monitoring data from the U.K. (n = 191 samples), Norway (n = 740) and Sweden (n = 531) for analysis against pH. 2. We tested new and existing acidification metrics developed nationally and used within the Northern Geographical Intercalibration Group. The new metrics were based on the acidification sensitivity of selected species and are proposed as a first step towards a new common indicator for acidification for Northern Europe. 3. Metrics were assessed according to responsiveness to mean pH, degree of nonlinearity in response and consistency in responses across countries. We used flexible, nonparametric regression models to explore various properties of the pressure,response relationships. Metrics were also analysed with humic content (total organic carbon above/below 5 mg L,1) as a covariate. 4. Most metrics responded clearly to pH, with the following metrics explaining most of the variance: Acid Water Indicator Community, Number of ephemeropteran families, Medin's index, Multimetric Indicator of Stream Acidification and the new metric ,Proportion of sensitive Ephemeroptera'. 5. Most metrics were significantly higher in humic than in clear-water rivers, suggesting smaller acidification effects in humic rivers. This result supports the proposed use of humic level as a typological factor in the assessment of acidification. 6. Some potentially important effects could not be considered in this study, such as the additional effects of metals, episodic acidification and the contrasting effects of natural versus anthropogenic acidity. We advocate further data collection and testing of metrics to incorporate these factors. [source]

    The influence of below-ground herbivory and defoliation of a legume on nitrogen transfer to neighbouring plants

    FUNCTIONAL ECOLOGY, Issue 2 2007
    E. AYRES
    Summary 1Both foliar and root herbivory can alter the exudation of carbon from plant roots, which in turn can affect nitrogen availability in the soil. However, few studies have investigated the effects of herbivory on N fluxes from roots, which can directly increase N availability in the soil and uptake by neighbouring plants. Moreover, the combined effects of foliar and root herbivory on N fluxes remains unexplored. 2We subjected the legume white clover (Trifolium repens L.) to defoliation (through clipping) and root herbivory (by an obligate root-feeding nematode, Heterodera trifolii Goggart) to examine how these stresses individually, and simultaneously, affected the transfer of T. repens -derived N to neighbouring perennial ryegrass (Lolium perenne L.) plants using 15N stable-isotope techniques. We also examined the effects of defoliation and root herbivory on the size of the soil microbial community and the growth response of L. perenne. 3Neither defoliation nor root herbivory negatively affected T. repens biomass. On the contrary, defoliation increased root biomass (34%) and total shoot production by T. repens (100%). Furthermore, defoliation resulted in a fivefold increase in T. repens -derived 15N recovered in L. perenne roots, and increased the size of the soil microbial biomass (77%). In contrast, root herbivory by H. trifolii slightly reduced 15N transfer from T. repens to L. perenne when T. repens root 15N concentration was included as a covariate, and root herbivory did not affect microbial biomass. Growth of L. perenne was not affected by any of the treatments. 4Our findings demonstrate that defoliation of a common grassland legume can substantially increase the transfer of its N to neighbouring plants by directly affecting below-ground N fluxes. These finding require further examination under field conditions but, given the prevalence of N-limitation of plant productivity in terrestrial ecosystems, increased transfer of N from legumes to non-N-fixing species could alter competitive interactions, with implications for plant community structure. [source]

    Abstract no.: 6 Endothelium-dependent relaxation by purinergic receptors in the aorta of apolipoprotein E-deficient mice

    A. Korda
    Previously we reported that the acetylcholine-induced relaxation in the isolated aorta of apolipoprotein E-deficient (apoE -/- ) mice deteriorates after the development of atherosclerotic plaques, but remains normal in adjacent, plaque-free segments. The present study investigated the presence of functional purinergic receptors in the murine aorta, and whether their function changes before or after the development of atherosclerosis. Endothelium-dependent relaxation was measured in aorta segments of apoE -/- , C57BL6 (WT) and human apoAI-overexpressing apoE -/- mice (apoAI/apoE -/- ) on regular chow. Rings were isometrically contracted with phenylephrine to 50% of their maximum force before performing cumulative concentration-response curves to different nucleotides or their stable analogues. After the functional study, the cross-sectional area of the plaque was determined in every segment. The nucleotides induced complete (UTP, UDP, ATP) or partial (ADP) relaxation that was abolished by endothelial cell removal or nitric oxide (NO) synthase inhibition. The responses pointed to the presence of functional P2y1, P2y2 or P2y4 receptors on endothelial cells. RT-PCR confirmed the presence of P2y1 and P2y4 mRNA in the aorta of WT mice. Nucleotide responses were unaltered in lesion-free apoE -/- mice (5 months). However, in atherosclerotic segments of apoE -/- mice (18 months), the relaxation to ATP was impaired compared to age-matched WT controls (maximum amplitude (Emax) 25 ± 14%, n = 6 vs. 90 ± 3%, n = 5, P < 0.01). A similar defect was seen for the stable analogue ATP-gamma-S (Emax 36 ± 12% vs. 86 ± 3%, P < 0.01). Atherosclerotic apoE -/- segments were less sensitive to the NO donor spermineNONOate (pD2 6.74 ± 0.18) than WT segments (7.25 ± 0.20), but maximum relaxation was unaltered. In non-atherosclerotic aorta segments of the same apoE -/- mice all relaxation responses remained normal and were not different from WT. Strong negative correlations (P < 0.001) existed between lesion size and the Emax for ATP (rs = ,0.82) and ATP-gamma-S (rs = ,0.73) in apoE -/- mice. ApoAI overexpression improved the purinergic responses (Emax ATP 64 ± 9%, ATP-gamma-S 64 ± 10%, n = 5) and these were not different from WT (P > 0.05). An analysis of covariance with plaque size as covariate suggested that this benefit was secondary to the strongly reduced plaque formation in apoAI/apoE -/- mice. It is concluded that functional P2 y receptors are present on murine aortic endothelium. Furthermore, endothelium-dependent purinergic relaxation declines after plaque development. This deterioration involves decreased bioavailability of NO rather than enhanced ATP degradation. The defect is, however, not systemic since the responses remain unaltered in plaque-free segments of atherosclerosis-prone apoE -/- mice. [source]

    Replication study of candidate genes for cognitive abilities: the Lothian Birth Cohort 1936

    L. M. Houlihan
    As the proportion of older people in societies has increased, research into the determinants of cognitive ageing has risen in importance. Genetic influences account for over 50% of the variance in adult cognitive abilities. Previous studies on cognition and illnesses with cognitive impairments have identified single nucleotide polymorphisms (SNPs) within candidate genes that might influence cognition or age-related cognitive change. This study investigated 10 candidate genes in over 1000 Scots: the Lothian Birth Cohort 1936 (LBC1936). These participants were tested on general cognitive ability (Scottish Mental Survey 1947) at age 11. At mean age 70, they completed the same general cognitive ability test and a battery of diverse cognitive tests. Nineteen SNPs in 10 genes previously associated with cognition, Alzheimer's disease or autism were genotyped in 1063 individuals. The genes include BDNF, COMT, DISC1, KL, NCSTN, PPP1R1B, PRNP, SHANK3, SORL1 and WRN. Linear regression analysis investigated the additive effect of each SNP on the cognitive variables, covarying for gender and age. Childhood cognitive ability was also included as a covariate to identify associations specifically with cognitive ageing. Certain SNPs reached the conventional significance threshold for association with cognitive traits or cognitive ageing in LBC1936 (P < 0.05). No SNPs reached the Bonferroni-level of significance (all P > 0.0015). Of the 10 genes, we discuss that COMT, KL, PRNP, PPP1R1B, SORL1 and WRN especially merit further attention for association with cognitive ability and/or age-related cognitive change. All results are also presented so that they are valuable for future meta-analyses of candidate genes for cognition. [source]

    Incorporating covariates in mapping heterogeneous traits: a hierarchical model using empirical Bayes estimation

    Swati Biswas
    Abstract Complex genetic traits are inherently heterogeneous, i.e., they may be caused by different genes, or non-genetic factors, in different individuals. So, for mapping genes responsible for these diseases using linkage analysis, heterogeneity must be accounted for in the model. Heterogeneity across different families can be modeled using a mixture distribution by letting each family have its own heterogeneity parameter denoting the probability that its disease-causing gene is linked to the marker map under consideration. A substantial gain in power is expected if covariates that can discriminate between the families of linked and unlinked types are incorporated in this modeling framework. To this end, we propose a hierarchical Bayesian model, in which the families are grouped according to various (categorized) levels of covariate(s). The heterogeneity parameters of families within each group are assigned a common prior, whose parameters are further assigned hyper-priors. The hyper-parameters are obtained by utilizing the empirical Bayes estimates. We also address related issues such as evaluating whether the covariate(s) under consideration are informative and grouping of families. We compare the proposed approach with one that does not utilize covariates and show that our approach leads to considerable gains in power to detect linkage and in precision of interval estimates through various simulation scenarios. An application to the asthma datasets of Genetic Analysis Workshop 12 also illustrates this gain in a real data analysis. Additionally, we compare the performances of microsatellite markers and single nucleotide polymorphisms for our approach and find that the latter clearly outperforms the former. Genet. Epidemiol. 2007. © 2007 Wiley-Liss, Inc. [source]

    Interpreting analyses of continuous covariates in affected sibling pair linkage studies

    Silke Schmidt
    Abstract Datasets collected for linkage analyses of complex human diseases often include a number of clinical or environmental covariates. In this study, we evaluated the performance of three linkage analysis methods when the relationship between continuous covariates and disease risk or linkage heterogeneity was modeled in three different ways: (1) The covariate distribution is determined by a quantitative trait locus (QTL), which contributes indirectly to the disease risk; (2) the covariate is not genetically determined, but influences the disease risk through statistical interaction with a disease susceptibility locus; (3) the covariate distribution differs in families linked or unlinked to a particular disease susceptibility locus. We analyzed simulated datasets with a regression-based QTL analysis, a nonparametric analysis of the binary affection status, and the ordered subset analysis (OSA). We found that a significant OSA result may be due to a gene that influences variability in the population distribution of a continuous disease risk factor. Conversely, a regression-based QTL analysis may detect the presence of gene-environment (G × E) interaction in a sample of primarily affected individuals. The contribution of unaffected siblings and the size of baseline lod scores may help distinguish between QTL and G × E models. As illustrated by a linkage study of multiplex families with age-related macular degeneration, our findings assist in the interpretation of analysis results in real datasets. They suggest that the side-by-side evaluation of OSA and QTL results may provide important information about the relationship of measured covariates with either disease risk or linkage heterogeneity. Genet. Epidemiol. 2007. © 2007 Wiley-Liss, Inc. [source]

    Simple estimates of haplotype relative risks in case-control data

    Benjamin 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]

    Heritability of plasma amyloid , in typical late-onset Alzheimer's disease pedigrees

    Nilufer Ertekin-Taner
    Abstract Plasma amyloid ,42 peptide (A,42) levels are significantly elevated in all genetic forms of early-onset Alzheimer's disease caused by familial Alzheimer's disease mutations or Down's syndrome. Moreover, recent studies have determined that both plasma A,42 and A,40 levels are significantly elevated in late-onset Alzheimer's disease (LOAD) patients, their cognitively normal first-degree relatives, and members of typical LOAD families when compared to appropriate controls. To determine the magnitude of the genetic component affecting plasma A, levels, we estimated the heritability of plasma A,42 and A,40 in 15 extended, multigenerational LOAD pedigrees, using a variance components method. Heritability estimates as high as 73 and 54% were found for plasma A,42 and A,40 levels, respectively. Inclusion of the ApoE ,4 dosage as a covariate was not found to have a significant effect on the heritability of these traits. These results suggest that genetic determinants other than ApoE account for a very substantial percentage of the phenotypic variance in plasma A, levels. The high heritability and the significant elevation of these traits in LOAD pedigrees suggest that at least some of the genetic determinants of plasma A, levels may lead to elevated A, and LOAD in these families. Thus, we suggest that plasma A, levels are quantitative traits that may be excellent surrogate markers for use in linkage analysis to identify loci that are important in typical LOAD. Genet. Epidemiol. 21:19,30, 2001. © 2001 Wiley-Liss, Inc. [source]

    Time to Send the Preemie Home?

    Additional Maturity at Discharge, Outcomes, Subsequent Health Care Costs
    Objective. To determine whether longer stays of premature infants allowing for increased physical maturity result in subsequent postdischarge cost savings that help counterbalance increased inpatient costs. Data Sources. One thousand four hundred and two premature infants born in the Northern California Kaiser Permanente Medical Care Program between 1998 and 2002. Study Design/Methods. Using multivariate matching with a time-dependent propensity score we matched 701 "Early" babies to 701 "Late" babies (developmentally similar at the time the earlier baby was sent home but who were discharged on average 3 days later) and assessed subsequent costs and clinical outcomes. Principal Findings. Late babies accrued inpatient costs after the Early baby was already home, yet costs after discharge through 6 months were virtually identical across groups, as were clinical outcomes. Overall, after the Early baby went home, the Late,Early cost difference was $5,016 (p<.0001). A sensitivity analysis suggests our conclusions would not easily be altered by failure to match on some unmeasured covariate. Conclusions. In a large integrated health care system, if a baby is ready for discharge (as defined by the typical criteria), staying longer increased inpatient costs but did not reduce postdischarge costs nor improve postdischarge clinical outcomes. [source]

    Serum bilirubin levels and mortality after myeloablative allogeneic hematopoietic cell transplantation,

    HEPATOLOGY, Issue 2 2005
    Ted A. Gooley
    Many patients who undergo hematopoietic cell transplantation experience liver injury. We examined the association of serum bilirubin levels with nonrelapse mortality by day +200, testing the hypothesis that the duration of jaundice up to a given point in time provides more prognostic information than either the maximum bilirubin value or the value at that point in time. We studied 1,419 consecutive patients transplanted from allogeneic donors. Total serum bilirubin values up to day +100, death, or relapse were retrieved,along with nonrelapse mortality by day +200 as an outcome measure,using Cox regression models with each bilirubin measure modeled as a time-dependent covariate. The bilirubin value at a particular point in time provided the best fit to the model for mortality. With bilirubin at a point in time modeled as an 8th-degree polynomial, an increase in bilirubin from 1 to 3 mg/dL is associated with a mortality hazard ratio of 6.42. An increase from 4 to 6 mg/dL yields a hazard ratio of 2.05, and an increase from 10 to 12 mg/dL yields a hazard ratio of 1.17. Among patients who were deeply jaundiced, survival was related to the absence of multiorgan failure and to higher platelet counts. In conclusion, the value of total serum bilirubin at a particular point in time after transplant carries more informative prognostic information than does the maximum or average value up to that point in time. The increase in mortality for a given increase in bilirubin value is larger when the starting value is lower. (HEPATOLOGY 2005,41:345,352.) [source]

    Children's Responses to Computer-Synthesized Speech in Educational Media: Gender Consistency and Gender Similarity Effects

    Kwan Min Lee
    This study examines children's social responses to gender cues in synthesized speech in a computer-based instruction setting. Eighty 5th-grade elementary school children were randomly assigned to one of the conditions in a full-factorial 2 (participant gender) × 2 (voice gender) × 2 (content gender) experiment. Results show that children apply gender-based social rules to synthesized speech. More specifically, children evaluate synthesized speech more positively, trust the speech more, and learn more effectively when voice gender matches either content gender (consistency attraction) and/or their own gender (similarity attraction). Children's computer self-efficacy was a significant covariate for their social responses to synthesized speech. Theoretical and practical implications of the current study for the design of educational media are discussed. [source]

    Auditory and visual distractor decrement in older worker manual assembly task learning: Impact of spatial reasoning, field independence, and level of education,

    S. F. Wiker
    This study examined the impact of age on manual assembly task learning in the presence of visual and auditory distracters. Manual assembly task learning (e.g., number of learning trials needed to obtain consistently accurate assembly and near asymptote performance times) was studied in men and women between 18 and 65 years of age. Higher spatial reasoning capabilities were associated with fewer trials to reach the learning criterion, faster manual assembly times, and material prophylaxis for the type of distractors addressed in this study that are likely to be encountered in the workplace. Years of formal education and field independence showed no impact on distractor-based decrements in task learning. For the oldest group of subjects (>50 years), concomitant presentation of visual and auditory distractors that are commonly encountered in industry were associated with a greater number of learning trials that were needed to achieve asymptotic manual assembly task learning. Spatial reasoning and field independence measures were lower in the older than in the younger age groups (p < 0.05). When spatial reasoning was treated as a covariate, however, nearly all age differences found in learning performance in the face of distractors were removed. The findings suggest that selection of workers based on spatial reasoning ability, rather than age, would yield better manual task learning in the face of visual and auditory distraction. © 2009 Wiley Periodicals, Inc. [source]

    A panel of ancestry informative markers for estimating individual biogeographical ancestry and admixture from four continents: utility and applications,

    HUMAN MUTATION, Issue 5 2008
    Indrani Halder
    Abstract Autosomal ancestry informative markers (AIMs) are useful for inferring individual biogeographical ancestry (I-BGA) and admixture. Ancestry estimates obtained from Y and mtDNA are useful for reconstructing population expansions and migrations in our recent past but individual genomic admixture estimates are useful to test for association of admixture with phenotypes, as covariate in association studies to control for stratification and, in forensics, to estimate certain overt phenotypes from ancestry. We have developed a panel of 176 autosomal AIMs that can effectively distinguish I-BGA and admixture proportions from four continental ancestral populations: Europeans, West Africans, Indigenous Americans, and East Asians. We present allele frequencies for these AIMs in all four ancestral populations and use them to assess the global apportionment of I-BGA and admixture diversity among some extant populations. We observed patterns of apportionment similar to those described previously using sex and autosomal markers, such as European admixture for African Americans (14.3%) and Mexicans (43.2%), European (65.5%) and East Asian affiliation (27%) for South Asians, and low levels of African admixture (2.8,10.8%) mirroring the distribution of Y E3b haplogroups among various Eurasian populations. Using simulation studies and pedigree analysis we show that I-BGA estimates obtained using this panel and a four-population model has a high degree of precision (average root mean square error [RMSE]=0.026). Using ancestry,phenotype associations we demonstrate that a large and informative AIM panel such as this can help reduce false-positive and false-negative associations between phenotypes and admixture proportions, which may result when using a smaller panel of less informative AIMs. Hum Mutat 29(5), 648,658, 2008. © 2008 Wiley-Liss, Inc. [source]

    Modeling tropical cyclone intensity with quantile regression

    Thomas H. Jagger
    Abstract Wind speeds from tropical cyclones (TCs) occurring near the USA are modeled with climate variables (covariates) using quantile regression. The influences of Atlantic sea-surface temperature (SST), the Pacific El Niño, and the North Atlantic oscillation (NAO) on near-coastal TC intensity are in the direction anticipated from previous studies using Poisson regression on cyclone counts and are, in general, strongest for higher intensity quantiles. The influence of solar activity, a new covariate, peaks near the median intensity level, but the relationship switches sign for the highest quantiles. An advantage of the quantile regression approach over a traditional parametric extreme value model is that it allows easier interpretation of model coefficients (parameters) with respect to changes to the covariates since coefficients vary as a function of quantile. It is proven mathematically that parameters of the Generalized Pareto Distribution (GPD) for extreme events can be used to estimate regression coefficients for the extreme quantiles. The mathematical relationship is demonstrated empirically using the subset of TC intensities exceeding 96 kt (49 m/s). Copyright © 2008 Royal Meteorological Society [source]

    Statins may reduce episodes of exacerbation and the requirement for intubation in patients with COPD: evidence from a retrospective cohort study

    A. I. Blamoun
    Summary Introduction:, Statins have diverse anti-inflammatory effects in addition to their lipid-lowering ability. This study assesses the rate of chronic obstructive pulmonary disease (COPD) exacerbation and intubations in patients taking statins. Methods:, This is a retrospective cohort study of 185 patients with COPD exacerbation, with a 1-year follow-up. Outcomes examined were repeat hospitalisation and intubations for COPD exacerbation. Baseline characteristics for which the p-value was , 0.10 were considered as covariates for inclusion in a multivariate model. Results:, The statin group had fewer episodes of exacerbation and required intubation fewer times than the subjects not receiving statins (p < 0.0001 for both outcomes). Unadjusted odds ratios (OR) for no statin use vs. statin use were 9.54 (95% CI: 4.54,20.02) for exacerbation and 10.47 (CI: 4.56,24.01) for intubation. The OR, adjusted for the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ORa), were 2.35 (CI: 1.01,5.50) for non-statin users exhibiting an exacerbation and 10.36 (CI: 2.77,38.76) for this group requiring intubation, compared with statin users. Similarly, ORa for long-acting ,2 agonists as a covariate were 3.01 (CI: 1.46,6.10) for exacerbation and 8.89 (CI: 3.67,21.32) for intubation. Time to outcome during the observation period was reduced by statins with the hazard ratio (HR) for exacerbation of 0.19 (CI: 0.06,0.14); HR for statins reducing intubation was 0.14 (95% CI: 0.10,0.30). Conclusions:, These data suggest that the use of statins may be associated with lower incidence of both exacerbations and intubations in patients with COPD. [source]

    Personality pathology and substance abuse in eating disorders: A longitudinal study

    Heather Thompson-Brenner PhD
    Abstract Objective: Substance abuse has been shown to predict poor outcome in eating disorder (ED) samples, and prior cross-sectional data on personality subtypes of EDs suggest that substance abuse is associated with dysregulated and possibly avoidant-insecure subtypes. This study investigates longitudinal associations between personality and substance use. Method: Personality pathology and substance use were assessed in 213 individuals with anorexia nervosa and bulimia nervosa at baseline; substance use was assessed at regular follow-up intervals over a 9-year period. Results: Of the five personality factors identified, the obsessional-sensitive and high-functioning types were negatively associated with substance abuse at baseline, while the behaviorally dysregulated type was positively associated with substance abuse at baseline. Longitudinal associations were observed, suggesting that obsessional-sensitive personality type was protective against the development of substance abuse. Longitudinal associations between the other personality types and substance abuse were nonsignificant after baseline substance abuse history was included as a covariate in the model. Conclusion: Substance use demonstrates cross-sectional associations with personality style, but substance abuse history appears to be the most important predictor of future substance abuse in women with eating disorders. © 2007 by Wiley Periodicals, Inc. Int J Eat Disord 2008 [source]

    Investigation of quality of the parental relationship as a risk factor for subclinical bulimia nervosa

    Tracey D. Wade
    Abstract Objective Previous literature suggests a link between the quality of the parental relationship and disordered eating in offspring. We investigated the relationship between offspring pyschopathology and the parental relationship using a population-based twin registry that contained 766 complete twin pairs. Method We used reports of twin lifetime psychopathology from the twins and quality of parental relationship and parental lifetime psychopathology from both parents. Results Poorer quality of the marital relationship predicted the presence of subclinical bulimia nervosa (SBN) using both mother's (odds ratio [OR] = 0.83, 95% confidence interval [CI]: 0.71,0.97) and father's (OR = 0.78, 95% CI: 0.62,0.97) reports. It also predicted the presence of generalized anxiety disorder (GAD) and alcohol dependence. SBN was still strongly predicted by the marital relationship when parental psychopathology was included as a covariate. Discussion These results are supportive of the notion that a conflictual and distant marital relationship can, at least partially, act as an environmental risk factor for SBN. © 2001 by John Wiley & Sons, Inc. Int J Eat Disord 30: 389,400, 2001. [source]

    MRI white matter hyperintensities, 1H-MR spectroscopy and cognitive function in geriatric depression: a comparison of early- and late-onset cases

    Tetsuhito Murata
    Abstract Background and Objectives Geriatric depression is often thought to differ from that at other times of adulthood. Recently, several studies have shown that the incidence of white matter hyperintense lessions identified by brain MRI is higher in patients with geriatric depression than in healthy elderly subjects, but a consensus has not yet been reached on the relationship between the severity of white matter lesions and either cognitive impairment or depressive symptoms. Method Forty-seven patients aged 50 to 75 years with major depression were divided into two groups based on age at onset of depression: early-onset (<,50 years) group (20 patients; mean age, 62.7,±,6.7) and late-onset (,50 years) group (27 patients; mean age, 65.6,±,5.4). The severity of hyperintense white matter lesions on MRI was classified by region, then a proton magnetic resonance spectroscopy (1H-MRS) focusing on the white matter of the frontal lobes, multidimensional neuropsychological tests and evaluation of depressive symptoms were conducted. Results The severity of the deep white matter lesions, the deterioration of cognitive function related to subcortical/frontal brain system and clinician-rated depressive symptoms were all more pronounced in the late-onset group compared with those in the early-onset group. It was further observed that the more severe the deep white matter lesions, the lower the levels of N-acetylaspartate/creatine. With the age of onset as the covariate, the patients with moderate deep white matter lesions had more pronounced cognitive impairment and clinician-rated depressive symptoms than those with none and/or mild lesions. Conclusion These results suggest that subcortical/frontal type cognitive impairment and the persistence of depressive symptoms in geriatric depression is related to moderate deep white matter lesions more often complicated in the late-onset group. The 1H-MRS findings were suggested to be a useful indicator of neuronal/axonal loss in the white matter of the frontal lobes which precedes cognitive impairment. Copyright © 2001 John Wiley & Sons, Ltd. [source]

    Graphing survival curve estimates for time-dependent covariates

    Lonni R. Schultz
    Abstract Graphical representation of statistical results is often used to assist readers in the interpretation of the findings. This is especially true for survival analysis where there is an interest in explaining the patterns of survival over time for specific covariates. For fixed categorical covariates, such as a group membership indicator, Kaplan-Meier estimates (1958) can be used to display the curves. For time-dependent covariates this method may not be adequate. Simon and Makuch (1984) proposed a technique that evaluates the covariate status of the individuals remaining at risk at each event time. The method takes into account the change in an individual's covariate status over time. The survival computations are the same as the Kaplan-Meier method, in that the conditional survival estimates are the function of the ratio of the number of events to the number at risk at each event time. The difference between the two methods is that the individuals at risk within each level defined by the covariate is not fixed at time 0 in the Simon and Makuch method as it is with the Kaplan-Meier method. Examples of how the two methods can differ for time dependent covariates in Cox proportional hazards regression analysis are presented. Copyright © 2002 Whurr Publishers Ltd. [source]

    Cyst Distribution and Hatching Pattern of Chirocephalus ruffoi (Crustacea, Anostraca) in an Experimental Undisturbed Pool

    Graziella Mura
    Abstract The pattern of cyst distribution in the absence of turbation and their hatching behaviour were studied in an outdoor artificial pool, where just differentiated adults of the anostracan Chirocephalus ruffoi (sex ratio 1:3) lived until it dried up. The horizontal and vertical distributions of cysts in the pool bed were determined. The comparison between cyst bank estimate (Mura, 2004) and the actual number of cysts counted in the pool bed revealed an estimate error of 20.9%. Resting eggs occurred only in the upper 2.5 cm thick soil sections and decreased within this section as depth increased. Peripheral areas of the pool contained significantly larger numbers of cysts than the central area. Multiway analysis on the results recorded in hatching success (nested ANOVA) revealed that the differences were significantly affected by initial soil conditions, treatment and vertical distribution of cysts. Among these factors, vertical distribution (sections nested in cores) was the most influential. Hatching success was significantly inversely related to depth. Differences in the timing of hatching depending on the above considered factors were also noted. A nearly synchronous hatching pattern was observed only for cysts from initially dry sediment of the uppermost layers. In all successively deeper layers, hatching showed multiple peaks and was increasingly delayed and erratic (already mentioned). ANCOVA within each of the experimental conditions revealed significant differences in hatching frequencies (time as covariate) depending on sediment depth. Within any given layer, ANCOVA revealed a significant influence of initial sediment conditions and treatment on the timing of hatching. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source]

    Time to establishment success for introduced signal crayfish in Sweden , a statistical evaluation when success is partially known

    Ullrika Sahlin
    Summary 1.,The signal crayfish Pacifastacus leniusculus is an invasive species in Sweden, threatening the red-listed nobel crayfish Astacus astacus through spreading the crayfish plague. Time-to-event models can handle censored data on such introduced populations for which the state (successful or not) is only partially known at the last observation, but even though data on introduced populations most often are censored, this type of model is usually not used for likelihood-based inference and predictions of the dynamics of establishing populations. 2.,We specified and fitted a probabilistic time-to-event model to be used to predict the time to successful establishment of signal crayfish populations introduced into Sweden. Important covariates of establishment success were found by the methods of ,model averaging' and ,hierarchical partitioning', considering model uncertainty and multi-colinearity, respectively. 3.,The hazard function that received the highest evidence based on the empirical data showed that the chances of establishment were highest in the time periods immediately following the first introduction. The model predicts establishment success to be <50% within 5 years after first introduction over the current distributional range of signal crayfish in Sweden today. 4.,Among covariates related to temperature, fish species and physical properties of the habitat, the length of the growing season was the most important and consistent covariate of establishment success. We found that establishment success of signal crayfish is expected to increase with the number of days when growth is possible, and decrease with the number of days with extremely high temperatures, which can be seen to approximate conditions of stress. 5.,Synthesis and applications. The results demonstrate lower establishment success of signal crayfish further north in Sweden, which may decrease the incentives of additional illegal introductions that may threaten the red-listed noble crayfish Astacus astacus. We provide a fully probabilistic statistical evaluation that quantifies uncertainty in the duration of the establishment stage that is useful for management decisions of invasive species. The combination of model averaging and hierarchical partitioning provides a comprehensive method to address multi-colinearity common to retrospective data on establishment success of invasive species. [source]