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Large Sample Sizes (large + sample_size)
Kinds of Large Sample Sizes Selected AbstractsProduction Efficiency and the Pricing of Audit Services,CONTEMPORARY ACCOUNTING RESEARCH, Issue 1 2003Nicholas Dopuch Abstract In this paper, we examine the relative efficiency of audit production by one of the then Big 6 public accounting firms for a sample of 247 geographically dispersed audits of U.S. companies performed in 1989. To test the relative efficiency of audit production, we use both stochastic frontier estimation (SFE) and data envelopment analysis (DEA). A feature of our research is that we also test whether any apparent inefficiencies in production, identified using SFE and DEA, are correlated with audit pricing. That is, do apparent inefficiencies cause the public accounting firm to reduce its unit price (billing rate) per hour of labor utilized on an engagement? With respect to results, we do not find any evidence of relative (within-sample) inefficiencies in the use of partner, manager, senior, or staff labor hours using SFE. This suggests that the SFE model may not be sufficiently powerful to detect inefficiencies, even with our reasonably large sample size. However, we do find apparent inefficiencies using the DEA model. Audits range from about 74 percent to 100 percent relative efficiency in production, while the average audit is produced at about an 88 percent efficiency level, relative to the most efficient audits in the sample. Moreover, the inefficiencies identified using DEA are correlated with the firm's realization rate. That is, average billing rates per hour fall as the amount of inefficiency increases. Our results suggest that there are moderate inefficiencies in the production of many of the subject public accounting firm's audits, and that such inefficiencies are economically costly to the firm. [source] Single layer centrifugation of stallion spermatozoa consistently selects the most robust spermatozoa from the rest of the ejaculate in a large sample sizeEQUINE VETERINARY JOURNAL, Issue 7 2010J. M. MORRELL Summary Reasons for performing study: An improvement in sperm quality after single layer centrifugation (SLC) has been seen in previous studies using small sample sizes (for example, n = 10 stallions). There is a need to investigate whether this improvement is repeatable over several breeding seasons with a larger number of stallions (n , 30 stallions). Objective: To make a retrospective analysis of the results of SLC performed on more than 250 sperm samples (176 ejaculates) from 31 stallions in 3 consecutive breeding seasons. Methods: Sperm quality (motility, proportion of morphologically normal spermatozoa and the proportion of spermatozoa with undamaged chromatin) was assessed before and after SLC. Results: All parameters of sperm quality examined were significantly better in sperm samples after SLC than in their unselected counterparts (P<0.001 for each parameter). The yield of spermatozoa obtained after SLC was influenced by the type of extender used and also by the concentration of spermatozoa in the original ejaculate, with fewer spermatozoa being recovered when the loading dose contained a high concentration of spermatozoa. The optimal concentration was approximately 100 × 106/ml. Sperm concentration in the samples loaded on to the colloid influenced the sperm yield while the type of semen extender affected sperm quality and survival. Furthermore, the scaled-up SLC method was found to be suitable for use with a range of ejaculates, with similar sperm kinematics being observed for standard and scaled-up preparations. Conclusions: SLC consistently improved the quality of stallion sperm samples from a large number of ejaculates. The method could be scaled-up, allowing larger volumes of ejaculate to be processed easily from a wide range of stallions. [source] Leptin is associated with craving in females with alcoholismADDICTION BIOLOGY, Issue 3-4 2004T Kraus The appetite and weight regulating peptide leptin was associated recently with alcohol craving during withdrawal. Nevertheless, correlations were only significant with craving displayed on the visual analogue scale for maximum craving during the previous week (VAS), and not if assessed with the highly validated Obsessive Compulsive Drinking Scale (OCDS). The objective of the following study, therefore, is to elucidate further the associations between the leptin system and craving concepts during alcohol withdrawal. A sufficiently large sample size should allow multiple statistical subgroup and confounder analyses. We prospectively investigated 102 chronic alcoholic inpatients (23 females, 79 males) during withdrawal on days 0 (admission), 1, 2 and days 7,-,10. In addition to the statistical analysis of the total sample, females and males were to be analysed separately. For detecting associations between leptin levels and craving scores multiple regression analysis was performed. Plasma leptin levels were determined, and craving for ethanol was assessed by both the OCDS and the VAS. Leptin plasma levels significantly increased during alcohol withdrawal compared to day 0, while all craving scores decreased. Body mass corrected leptin plasma levels predicted craving on day 0 in the OCDS total score (R ,=,0.55, F ,=,7.91, df,=,1.19, p ,<,0.05) and in the OCDS obsessive subscore (R ,=,0.57, F <,=,8.48, df,=,1.19, p ,<,0.05) in females. Neither in males nor in the total population did multiple regression analysis reveal any significant results. Leptin levels seem to change during inpatient alcohol withdrawal. In a multivariate model, correlations between leptin levels and the highly validated craving scores of the OCDS can only be assumed in females. Hence, gender differences have to be taken into account when searching for neurobiological models of alcohol craving. [source] The International Quotidian Dialysis Registry: Annual report 2005HEMODIALYSIS INTERNATIONAL, Issue 3 2005Gihad Nesrallah Abstract The International Quotidian Dialysis Registry was designed to collect data describing treatments, characteristics, and outcomes of patients treated with quotidian hemodialysis (HD) worldwide. In July 2004, North American centers were first invited to enroll patients. By March 1, 2005, a total of 70 nocturnal and 8 short-daily HD patients from three Canadian and two US centers were enrolled. As recruitment continues, projected enrollment for 2005 may exceed 200 patients from North America alone. Preliminary analyses indicate that the current registry cohort is younger (mean age, 49.5 ± 1.6 years) and carries a lower burden of comorbidity than the overall North American HD population. The low event rate expected in this cohort underlines the need for a large sample size if an appropriately powered survival study is to be undertaken. Increasing recruitment in the United States by including HD centers owned or managed by large dialysis organizations, and beginning overseas collaborations to include Australia, New Zealand, Europe, and South America will be the primary areas of focus for 2005. [source] Antiretroviral effects on HIV-1 RNA, CD4 cell count and progression to AIDS or death: a meta-regression analysisHIV MEDICINE, Issue 10 2008EJ Mills Objective Governments, clinicians and drug-licensing bodies have adopted changes in CD4 cell counts and HIV-1 RNA levels as evidence of effectiveness for new therapeutic interventions. We aimed to determine the strength of the association between the magnitude of the effect of changes in CD4 cell count and HIV-1 RNA and progression to AIDS or death in the highly active antiretroviral therapy (HAART) era. Methods We identified all randomized clinical trials (RCTs) evaluating the effect of HAART on both clinical and surrogate endpoints (1994 to September 2006). We performed a meta-regression and weighted linear regression. We additionally estimated potential RCT sample sizes that would be required to assess the effectiveness of new interventions in terms of clinical endpoints. Results We included data from 178 RCTs. We were unable to demonstrate a strong relationship at any time-point. Specifically, this was the case when CD4 T-cell change and clinical outcomes were examined at week 24 [coefficient ,0.01, 95% confidence interval (CI) ,0.03 to 0.001, P=0.54], week 48 (coefficient ,0.01, 95% CI ,0.02 to 0.001, P=0.83) and week 96 (coefficient 0.00, 95% CI ,0.03 to 0.04, P=0.76). This was also the case when viral load was examined as a surrogate marker. Given the small number of clinical events occurring in new interventional RCTs, any RCT aiming to evaluate clinical endpoints within these time-points would require an exceptionally large sample size. Conclusions Our findings indicate that, within short-term clinical trial settings, it is not possible to estimate the proportion of treatment effect associated with surrogate endpoints. [source] Vitamin D receptor gene polymorphisms are associated with increased risk and progression of renal cell carcinoma in a Japanese populationINTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2007Wataru Obara Aim: Biological and epidemiologic data suggest that 1 alpha, 25 dihydroxyvitamin D3 (1,25(OH)2D3) levels may influence development of renal cell carcinoma. The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of 1,25(OH)2D3 and additionally interacts with other cell signaling pathways that influence cancer progression. VDR gene polymorphisms may play an important role in risk of incidence for various malignant tumors. This study investigated whether VDR gene polymorphisms were associated with increased risk and prognosis of renal cell carcinoma (RCC) in a Japanese population. Methods: To analyze risk of RCC depending on VDR polymorphism, a case,control association study was performed. The VDR gene polymorphisms at three locations, BsmI, ApaI and TaqI, were genotyped in 135 RCC patients and 150 controls in a Japanese population. Logistic regression models were used to assess the genetic effects on prognosis. Results: Significant differences in the ApaI genotype were observed between RCC patients and controls (,2 = 6.90, P = 0.032). No statistical significant difference was found in the BsmI and TaqI polymorphisms. The frequency of the AA genotype in the ApaI polymorphism was significantly higher in the RCC patients than in the controls (odds ratio, 2.59; 95% confidence intervals, 1.21,5.55; P = 0.012). Multivariate regression analysis showed that the AA genotype was an independent prognostic factor for cause-specific survival (relative risk 3.3; P = 0.038). Conclusion: The AA genotype at the ApaI site of the VDR gene may be a risk of incidence and poor prognosis factor for RCC in the Japanese population. Additional studies with a large sample size and investigation of the functional significance of the ApaI polymorphism in RCC cells are warranted. [source] Meta-Analysis of Genome-Wide Scans Provides Evidence for Sex- and Site-Specific Regulation of Bone Mass,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2007John PA Ioannidis Abstract Several genome-wide scans have been performed to detect loci that regulate BMD, but these have yielded inconsistent results, with limited replication of linkage peaks in different studies. In an effort to improve statistical power for detection of these loci, we performed a meta-analysis of genome-wide scans in which spine or hip BMD were studied. Evidence was gained to suggest that several chromosomal loci regulate BMD in a site-specific and sex-specific manner. Introduction: BMD is a heritable trait and an important predictor of osteoporotic fracture risk. Several genome-wide scans have been performed in an attempt to detect loci that regulate BMD, but there has been limited replication of linkage peaks between studies. In an attempt to resolve these inconsistencies, we conducted a collaborative meta-analysis of genome-wide linkage scans in which femoral neck BMD (FN-BMD) or lumbar spine BMD (LS-BMD) had been studied. Materials and Methods: Data were accumulated from nine genome-wide scans involving 11,842 subjects. Data were analyzed separately for LS-BMD and FN-BMD and by sex. For each study, genomic bins of 30 cM were defined and ranked according to the maximum LOD score they contained. While various densitometers were used in different studies, the ranking approach that we used means that the results are not confounded by the fact that different measurement devices were used. Significance for high average rank and heterogeneity was obtained through Monte Carlo testing. Results: For LS-BMD, the quantitative trait locus (QTL) with greatest significance was on chromosome 1p13.3-q23.3 (p = 0.004), but this exhibited high heterogeneity and the effect was specific for women. Other significant LS-BMD QTLs were on chromosomes 12q24.31-qter, 3p25.3-p22.1, 11p12-q13.3, and 1q32-q42.3, including one on 18p11-q12.3 that had not been detected by individual studies. For FN-BMD, the strongest QTL was on chromosome 9q31.1-q33.3 (p = 0.002). Other significant QTLs were identified on chromosomes 17p12-q21.33, 14q13.1-q24.1, 9q21.32-q31.1, and 5q14.3-q23.2. There was no correlation in average ranks of bins between men and women and the loci that regulated BMD in men and women and at different sites were largely distinct. Conclusions: This large-scale meta-analysis provided evidence for replication of several QTLs identified in previous studies and also identified a QTL on chromosome 18p11-q12.3, which had not been detected by individual studies. However, despite the large sample size, none of the individual loci identified reached genome-wide significance. [source] Formulation of the DETECT Population Parameter and Evaluation of DETECT Estimator BiasJOURNAL OF EDUCATIONAL MEASUREMENT, Issue 3 2006Louis A. Roussos The development of the DETECT procedure marked an important advancement in nonparametric dimensionality analysis. DETECT is the first nonparametric technique to estimate the number of dimensions in a data set, estimate an effect size for multidimensionality, and identify which dimension is predominantly measured by each item. The efficacy of DETECT critically depends on accurate, minimally biased estimation of the expected conditional covariances of all the item pairs. However, the amount of bias in the DETECT estimator has been studied only in a few simulated unidimensional data sets. This is because the value of the DETECT population parameter is known to be zero for this case and has been unknown for cases when multidimensionality is present. In this article, integral formulas for the DETECT population parameter are derived for the most commonly used parametric multidimensional item response theory model, the Reckase and McKinley model. These formulas are then used to evaluate the bias in DETECT by positing a multidimensional model, simulating data from the model using a very large sample size (to eliminate random error), calculating the large-sample DETECT statistic, and finally calculating the DETECT population parameter to compare with the large-sample statistic. A wide variety of two- and three-dimensional models, including both simple structure and approximate simple structure, were investigated. The results indicated that DETECT does exhibit statistical bias in the large-sample estimation of the item-pair conditional covariances; but, for the simulated tests that had 20 or more items, the bias was small enough to result in the large-sample DETECT almost always correctly partitioning the items and the DETECT effect size estimator exhibiting negligible bias. [source] Forecasting volatility with support vector machine-based GARCH modelJOURNAL OF FORECASTING, Issue 4 2010Shiyi Chen Abstract Recently, support vector machine (SVM), a novel artificial neural network (ANN), has been successfully used for financial forecasting. This paper deals with the application of SVM in volatility forecasting under the GARCH framework, the performance of which is compared with simple moving average, standard GARCH, nonlinear EGARCH and traditional ANN-GARCH models by using two evaluation measures and robust Diebold,Mariano tests. The real data used in this study are daily GBP exchange rates and NYSE composite index. Empirical results from both simulation and real data reveal that, under a recursive forecasting scheme, SVM-GARCH models significantly outperform the competing models in most situations of one-period-ahead volatility forecasting, which confirms the theoretical advantage of SVM. The standard GARCH model also performs well in the case of normality and large sample size, while EGARCH model is good at forecasting volatility under the high skewed distribution. The sensitivity analysis to choose SVM parameters and cross-validation to determine the stopping point of the recurrent SVM procedure are also examined in this study. Copyright © 2009 John Wiley & Sons, Ltd. [source] Forensic Age-at-Death Estimation from the Human Sacrum,JOURNAL OF FORENSIC SCIENCES, Issue 2 2009Nicholas V. Passalacqua M.S. Abstract:, A new method is described here that incorporates seven developmental and degenerative changes for estimating chronological age from morphological features of the human sacrum. The construction of this method involved multiple stages of trait identification, character-state definition and age correlation, rank-order phase development, and percent-correct sample testing with phase and sample aggregation, all of which resulted in a six-phase component system for application on modern individuals. This phase system was first developed on European American male and female samples from the Hamann-Todd collection; then tested on African American male and female Hamann-Todd samples as well as European American male and females from the WM Bass collection to examine possible sex and/or ancestry differences. Variation in age estimates due to sex and ancestry was negligible; thus, the multiple samples were all pooled creating a robust method with a large sample size. Overall age ranges increase in width at two standard deviations as is expected from degenerative age-related processes but retain utility in forensic situations. [source] Genetic variability is unrelated to growth and parasite infestation in natural populations of the European eel (Anguilla anguilla)MOLECULAR ECOLOGY, Issue 22 2009J. M. PUJOLAR Abstract Positive correlations between individual genetic heterozygosity and fitness-related traits (HFCs) have been observed in organisms as diverse as plants, marine bivalves, fish or mammals. HFCs are not universal and the strength and stability of HFCs seem to be variable across species, populations and ages. We analysed the relationship between individual genetic variability and two different estimators of fitness in natural samples of European eel, growth rate (using back-calculated length-at-age 1, 2 and 3) and parasite infestation by the swimbladder nematode Anguillicola crassus. Despite using a large data set of 22 expressed sequence tags-derived microsatellite loci and a large sample size of 346 individuals, no heterozygote advantage was observed in terms of growth rate or parasite load. The lack of association was evidenced by (i) nonsignificant global HFCs, (ii) a Multivariate General Linear Model showing no effect of heterozygosity on fitness components, (iii) single-locus analysis showing a lower number of significant tests than the expected false discovery rate, (iv) sign tests showing only a significant departure from expectations at one component, and, (v) a random distribution of significant single-locus HFCs that was not consistent across fitness components or sampling sites. This contrasts with the positive association observed in farmed eels in a previous study using allozymes, which can be explained by the nature of the markers used, with the allozyme study including many loci involved in metabolic energy pathways, while the expressed sequence tags-linked microsatellites might be located in genes or in the proximity of genes uncoupled with metabolism/growth. [source] The incidence of mid-infrared excesses in G and K giantsMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 2 2008Mark H. Jones ABSTRACT Using photometric data from the Two-Micron All-Sky Survey (2MASS) and GLIMPSE catalogues, I investigate the incidence of mid-infrared (mid-IR) excesses (,10 ,m) in G and K stars of luminosity class III. In order to obtain a large sample size, stars are selected using a near-IR colour,magnitude diagram. Sources which are candidates for showing mid-IR excess are carefully examined and modelled to determined whether they are likely to be G/K giants. It is found that mid-IR excesses are present at a level of (1.8 ± 0.4) × 10,3. While the origin of these excesses remains uncertain, it is plausible that they arise from debris discs around these stars. I note that the measured incidence is consistent with a scenario in which dust lifetimes in debris discs are determined by Poynting,Robertson drag rather than by collisions. [source] The association between pubertal status and sleep duration and quality among a nationally representative sample of U. S. AdolescentsAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 4 2005Kristen L. Knutson Many hormones play important roles in both pubertal development and sleep regulation. Because of the possible consequences of impaired sleep, including impaired health and cognition, it is important to examine whether an association between pubertal stage and sleep exists. The aim of this analysis is to examine the association between sleep and adolescent growth and developmental stage in a large sample of adolescents ages 12,16 years from a nationally representative longitudinal study. This analysis used the public-use data set of the National Longitudinal Study of Adolescent Health, an extensive survey of health and behavior among adolescents in the United States. The study included two interviews approximately 1 year apart. Pubertal development, sleep variables, and height are self-reported. Pubertal development scores were calculated by summing responses to three questions for each sex. The sleep variables include sleep duration, frequent insomnia (once/week or more), frequently waking tired (once/week or more), and insufficient sleep. The results indicate a sex difference in the association between sleep problems and pubertal development. Among females, there was a significant increase in sleep problems with increasing pubertal development score, but not among males. The negative association between sleep duration and pubertal development score, however, was significant in both males and females. There is no association between sleep duration and height velocity (inches/year) in this sample. The results, which are based on a large sample size, warrant further examination with more objective measures into the association between sleep and growth and development among adolescents. Am. J. Hum. Biol. 17:418,424, 2005.© 2005 Wiley-Liss, Inc. [source] Magnification devices for endodontic therapyAUSTRALIAN DENTAL JOURNAL, Issue 4 2009M Del Fabbro Background:, After the introduction of microsurgical principles in endodontics, involving new techniques for root canal treatment, there has been a continuous search for enhancing the visualization of the surgical field. It would be interesting to know if the technical advantages for the operator brought in by magnification devices like surgical microscope, endoscope and magnifying loupes, are also associated with advantages for the patient, in terms of improvement of clinical and radiographic outcomes. Objectives:, The purpose of this systematic review was to evaluate and compare the effects of endodontic treatment performed with the aid of magnification devices versus endodontic treatment without magnification devices. We also aimed at comparing among them the different magnification devices used in endodontics (microscope, endoscope, magnifying loupes). Search strategy:, The Cochrane Oral Health Group Trials Register, CENTRAL, MEDLINE and EMBASE were searched with appropriate search strategies. Handsearching included nine dental journals. The bibliographies of relevant clinical trials and relevant articles were checked for identifying studies outside the handsearched journals. Seven manufacturers of instruments in the field of endodontics and/or endodontic surgery, as well as the authors of the identified randomized controlled trials (RCTs) were contacted in order to identify unpublished or ongoing RCTs. There were no language restrictions. The last electronic search was conducted on 2nd April 2009, and the last handsearching was undertaken on 31st January 2009. Selection criteria:, All randomized and quasi-randomized trials comparing endodontic therapy performed with or without using one or more types of magnification device, as well as randomized and quasi-randomized trials comparing two or more magnification devices used as an adjunct to endodontic therapy were considered. Data collection and analysis:, Screening of studies and data extraction were conducted independently and in duplicate. The Cochrane Collaboration statistical guidelines were to be followed for data synthesis. Main results:, No trial could be included in the present review. All of the prospective trials that were identified, all dealing with endodontic surgery, had to be excluded for various reasons. Only one RCT was identified comparing three magnificators (magnifying loupes, surgical microscope, endoscope) in endodontic surgery. No RCT was found that compared the outcome of endodontic therapy using or without using a given magnification device. Authors' conclusions:, No objective conclusion can be drawn from the results of this review as no article was identified in the current literature that satisfied the criteria for inclusion. It is unknown if and how the type of magnification device affects the treatment outcome, considering the high number of factors that may have a significant impact on the success of endodontic surgical procedure. This should be investigated by further long-term RCTs with large sample size. Technical advantages of magnificators have been widely reported in low evidence level studies, but they should be systematically addressed to know if there can be the clinical indication for using a given magnification device for specific clinical situations, such as for molar teeth, or if they can all be used interchangeably. Well-designed RCTs should also be performed to determine the true difference in terms of treatment success rates between using or not using a magnification device in both conventional and surgical endodontic treatment, if any exist. Plain language summary:, Magnification devices for endodontic therapy. There are no data to draw a sound conclusion on the effect of adopting either a microscope, an endoscope, or magnifying loupes for better visualization in endodontic therapy, in terms of clinical outcomes. Though the use of magnification devices has often been associated with technical advantages for the operator and with an improved management of the root canal due to a better visualization of the operative field, it still has to be demonstrated that their use may lead to an improved treatment success rate. More long-term well-designed randomized trials with a large sample size are urgently needed to address the issues of the present review. [source] Magnetic resonance imaging for the detection of bone marrow involvement in malignant lymphomaBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2008Thomas C. Kwee Summary This study systematically reviewed the published data regarding the sensitivity of magnetic resonance imaging (MRI) compared with bone marrow biopsy as reference standard for the detection of bone marrow involvement in patients with malignant lymphoma. A systematic search for relevant studies was performed of the PubMed/MEDLINE and Embase databases. Two reviewers independently assessed the methodological quality of each study and the sensitivity of the included studies was calculated. The 11 included studies had moderate methodological quality. Sensitivity of MRI for the detection of bone marrow involvement ranged from 50% to 100%, with a median of 100%. MRI is probably sufficiently sensitive to rule out bone marrow involvement in patients with malignant lymphoma. However, a well-designed study with a large sample size is needed to confirm current results. [source] Microevolution in agricultural environments: how a traditional Amerindian farming practice favours heterozygosity in cassava (Manihot esculenta Crantz, Euphorbiaceae)ECOLOGY LETTERS, Issue 2 2005Benoît Pujol Abstract We demonstrate a novel case of selection for heterozygosity in nature, involving inadvertent human selection on a population of domesticated plants. Amerindian farmers propagate cassava (Manihot esculenta) clonally by cuttings. Seedlings also appear spontaneously in fields, and farmers allow them to grow, later using some for cuttings. These ,volunteers' contribute new genotypes. However, many are inbred, whereas multiplied clones are highly heterozygous. We demonstrate the selective retention of heterozygous volunteers. When farmers weeded fields, they killed small volunteers, but retained large ones. Plant size and heterozygosity were correlated, and both increased after weeding. The process we document allows maintenance of genotypically diverse and heterozygous clonal stocks. Demonstrating heterosis in nature usually requires large sample sizes, but novel features of our system allowed escape of this constraint. Traditional agroecosystems offer unusual opportunities for the microevolutionary studies required to give on-farm conservation of genetic resources a solid scientific basis. [source] Analysis of Genetically Complex EpilepsiesEPILEPSIA, Issue 2005Ruth Ottman Summary:, During the last decade, great progress has been made in the discovery of genes that influence risk for epilepsy. However, these gene discoveries have been in epilepsies with Mendelian modes of inheritance, which comprise only a tiny fraction of all epilepsy. Most people with epilepsy have no affected relatives, suggesting that the great majority of all epilepsies are genetically complex: multiple genes contribute to their etiology, none of which has a major effect on disease risk. Gene discovery in the genetically complex epilepsies is a formidable task. It is unclear which epilepsy phenotypes are most advantageous to study, and chromosomal localization and mutation detection are much more difficult than in Mendelian epilepsies. Association studies are very promising for the identification of complex epilepsy genes, but we are still in the earliest stages of their application in the epilepsies. Future studies should employ very large sample sizes to ensure adequate statistical power, clinical phenotyping methods of the highest quality, designs and analytic techniques that control for population stratification, and state-of-the-art molecular methods. Collaborative studies are essential to achieve these goals. [source] Variation in leaf functional trait values within and across individuals and species: an example from a Costa Rican dry forestFUNCTIONAL ECOLOGY, Issue 1 2010Catherine M. Hulshof Summary 1.,Patterns of species co-existence and species diversity in plant communities remain an important research area despite over a century of intensive scrutiny. To provide mechanistic insight into the rules governing plant species co-existence and diversity, plant community ecologists are increasingly quantifying functional trait values for the species found in a wide range of communities. 2.,Despite the promise of a quantitative functional trait approach to plant community ecology, we suggest that, along with examining trait variation across species, an assessment of trait variation within species should also be a key component of a trait-based approach to community ecology. Variability within and between individuals and populations is likely widespread due to plastic responses to highly localized abiotic and biotic interactions. 3.,In this study, we quantify leaf trait variation within and across ten co-existing tree species in a dry tropical forest in Costa Rica to ask: (i) whether the majority of trait variation is located between species, within species, within individuals or within the leaves themselves; (ii) whether trait values collected using standardized methods correlate with those collected using unstandardized methods; and (iii) to what extent can we differentiate plant species on the basis of their traits? 4.,We find that the majority of variation in traits was often explained by between species differences; however, between leaflet trait variation was very high for compound-leaved species. We also show that many species are difficult to reliably differentiate on the basis of functional traits even when sampling many individuals. 5.,We suggest an ideal sample size of at least 10, and ideally 20, individuals be used when calculating mean trait values for individual species for entire communities, though even at large sample sizes, it remains unclear if community level trait values will allow comparisons on a larger geographic scale or if species traits are generally similar across scales. It will thus be critical to account for intraspecific variation by comparing species mean trait values across space in multiple microclimatic environments within local communities and along environmental gradients. Further, quantifying trait variability due to plasticity and inheritance will provide a better understanding of the underlying patterns and drivers of trait variation as well as the application of functional traits in outlining mechanisms of species co-existence. [source] Comprehensive linkage and linkage heterogeneity analysis of 4344 sibling pairs affected with hypertension from the Family Blood Pressure ProgramGENETIC EPIDEMIOLOGY, Issue 3 2007Tiffany A. Greenwood Abstract Linkage analyses of complex, multifactorial traits and diseases, such as essential hypertension, have been difficult to interpret and reconcile. Many published studies provide evidence suggesting that different genes and genomic regions influence hypertension, but knowing which of these studies reflect true positive results is challenging. The reasons for this include the diversity of analytical methods used across these studies, the different samples and sample sizes in each study, and the complicated biological underpinnings of hypertension. We have undertaken a comprehensive linkage analysis of 371 autosomal microsatellite markers genotyped on 4,334 sibling pairs affected with hypertension from five ethnic groups sampled from 13 different field centers associated with the Family Blood Pressure Program (FBPP). We used a single analytical technique known to be robust to interpretive problems associated with a lack of completely informative markers to assess evidence for linkage to hypertension both within and across the ethnic groups and field centers. We find evidence for linkage to a number of genomic regions, with the most compelling evidence from analyses that combine data across field center and ethnic groups (e.g., chromosomes 2 and 9). We also pursued linkage analyses that accommodate locus heterogeneity, which is known to plague the identification of disease susceptibility loci in linkage studies of complex diseases. We find evidence for linkage heterogeneity on chromosomes 2 and 17. Ultimately our results suggest that evidence for linkage heterogeneity can only be detected with large sample sizes, such as the FBPP, which is consistent with theoretical sample size calculations. Genet. Epidemiol. 2007. © 2007 Wiley-Liss, Inc. [source] Environmental enrichment: past, present and futureINTERNATIONAL ZOO YEARBOOK, Issue 1 2003D. J. SHEPHERDSON Intereat and activity in the field of environmental enrichment have blossomed over the last decade, and the sophistication and utility of the concepts underlying enrichment have grown correspondingly. Combined with the enthusiasm of animal keepers, this has resulted in demonstrable improvements to the welfare of zoo animals. The next step is for enrichment to be incorporated systematically into the husbandry programmes of all zoos and aquariums, and this is beginning to happen. Detailed systematic studies utilizing large sample sizes are needed to test and refine hypotheses in order to ensure that enrichment activities continue to be effective in the future. [source] Study Design in Osteoporosis: A European Perspective,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2003Ja Kanis MD The advent of effective agents for the treatment of osteoporosis has led to the view that placebo-controlled trials to test new agents for efficacy are no longer appropriate. Rather, studies of superiority, equivalence, or non-inferiority have been recommended. Such studies require very large sample sizes, and the burden of osteoporotic fracture in a trial setting is substantially increased. Studies of equivalence cannot be unambiguously interpreted because the variance in effect of active comparator agents is too large in osteoporosis. If fracture studies are required by regulatory agencies, there is still a requirement for placebo-controlled studies, although perhaps of shorter duration than demanded at present. [source] On the use of non-local prior densities in Bayesian hypothesis testsJOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES B (STATISTICAL METHODOLOGY), Issue 2 2010Valen E. Johnson Summary., We examine philosophical problems and sampling deficiencies that are associated with current Bayesian hypothesis testing methodology, paying particular attention to objective Bayes methodology. Because the prior densities that are used to define alternative hypotheses in many Bayesian tests assign non-negligible probability to regions of the parameter space that are consistent with null hypotheses, resulting tests provide exponential accumulation of evidence in favour of true alternative hypotheses, but only sublinear accumulation of evidence in favour of true null hypotheses. Thus, it is often impossible for such tests to provide strong evidence in favour of a true null hypothesis, even when moderately large sample sizes have been obtained. We review asymptotic convergence rates of Bayes factors in testing precise null hypotheses and propose two new classes of prior densities that ameliorate the imbalance in convergence rates that is inherited by most Bayesian tests. Using members of these classes, we obtain analytic expressions for Bayes factors in linear models and derive approximations to Bayes factors in large sample settings. [source] Genome-wide association studies of cardiovascular risk factors: design, conduct and interpretationJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2009J. C. BIS Summary., Relying on known biology, candidate-gene studies have been only modestly successful in identifying genetic variants associated with cardiovascular risk factors. Genome-wide association (GWA) studies, in contrast, allow broad scans across millions of loci in search of unsuspected genetic associations with phenotypes. The large numbers of statistical tests in GWA studies and the large sample sizes required to detect modest-sized associations have served as a powerful incentive for the development of large collaborative efforts such as the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium [1]. This article uses published data on three phenotypes, fibrinogen, uric acid, and electrocardiographic QT interval duration, from the CHARGE Consortium to describe several methodologic issues in the design, conduct, and interpretation of GWA studies, including the use of imputation and the need for additional genotyping. Even with large studies, novel genetic loci explain only a small proportion of the variance of cardiovascular phenotypes. [source] Massive parallel MHC genotyping: titanium that shinesMOLECULAR ECOLOGY, Issue 9 2009K. MATHIAS WEGNER The power of population genetic analyses is often limited by sample size resulting from constraints in financial resources and time to genotype large numbers of individuals. This particularly applies to nonmodel species where detailed genomic knowledge is lacking. Next-generation sequencing technology using primers ,tagged' with an individual barcode of a few nucleotides offers the opportunity to genotype hundreds of individuals at several loci in parallel (Binladen et al. 2007; Meyer et al. 2008). The large number of sequence reads can also be used to identify artefacts by frequency distribution thresholds intrinsically determined for each run and data set. In Babik et al. (2009), next-generation deep sequencing was used to genotype several major histocompatibility complex (MHC) class IIB loci of the European bank vole (Fig. 1). Their approach can be useful for many researchers working with complex multiallelic templates and large sample sizes. Figure 1. Hypothetical example of parallel genotyping of two individuals using individually bar-coded primers. Polymerase chain reactions (PCRs) are performed separately for each individual using a forward primer with a unique Tag -sequence of four nucleotides. After sequencing of pooled PCR products, sequences can be sorted by their forward primer Tag (Tag -sorting error rate was estimated < 0.1%). Rare sequences most likely represent artefacts and due to the large amount of sequences obtained (up to 106) the artefact threshold can be determined intrinsically for each data set and was estimated to be around 3% in the case of bank vole MHC class IIB genes (Babik et al. 2009). Photos by Gabriela Bydlon. [source] Evolutionary and statistical properties of three genetic distancesMOLECULAR ECOLOGY, Issue 8 2002Steven T. Kalinowski Abstract Many genetic distances have been developed to summarize allele frequency differences between populations. I review the evolutionary and statistical properties of three popular genetic distances: DS, DA, and ,, using computer simulation of two simple evolutionary histories: an isolation model of population divergence and an equilibrium migration model. The effect of effective population size, mutation rate, and mutation mechanism upon the parametric value between pairs of populations in these models explored, and the unique properties of each distance are described. The effect of these evolutionary parameters on study design is also investigated and similar results are found for each genetic distance in each model of evolution: large sample sizes are warranted when populations are relatively genetically similar; and loci with more alleles produce better estimates of genetic distance. [source] Replicated batch means for steady-state simulationsNAVAL RESEARCH LOGISTICS: AN INTERNATIONAL JOURNAL, Issue 6 2006Nilay Tan, k Argon Abstract This paper studies a new steady-state simulation output analysis method called replicated batch means in which a small number of replications are conducted and the observations in these replications are grouped into batches. This paper also introduces and compares methods for selecting the initial state of each replication. More specifically, we show that confidence intervals constructed by the replicated batch means method are valid for large batch sizes and derive expressions for the expected values and variances of the steady-state mean and variance estimators for stationary processes and large sample sizes. We then use these expressions, analytical examples, and numerical experiments to compare the replicated batch means method with the standard batch means and multiple replications methods. The numerical results, which are obtained from an AR(1) process and a small, nearly-decomposable Markov chain, show that the multiple replications method often gives confidence intervals with poorer coverage than the standard and replicated batch means methods and that the replicated batch means method, implemented with good choices of initialization method and number of replications, provides confidence interval coverages that range from being comparable with to being noticeably better than coverages obtained by the standard batch means method. © 2006 Wiley Periodicals, Inc. Naval Research Logistics, 2006 [source] Adult primary extragonadal germ cell tumors: Treatment results and long-term follow-upPEDIATRIC BLOOD & CANCER, Issue 1 2003Argon Andac MD Abstract Background Primary extragonadal germ cell tumors (PEGCT) are rare neoplasms. They have a poor prognosis, different behavior, and natural course compared to their gonadal counterparts. Both primary and salvage treatment of these tumors constitute a challenge. We retrospectively evaluated the clinicopathologic status, therapeutic implications, and outcome of our patients with PEGCT. Procedure Between 1991 and 2000, 18 patients with PEGCT (median age 31 years; range 17,63), diagnosed with tru-cut biopsy and treated with cisplatin-based chemotherapy, were evaluated in respect to treatment response and outcome. Results Cisplatin-based chemotherapy achieved a complete response rate of 27.8% and a partial response rate of 55.5%. Overall response rate was 83.3%. Only three patients were unresponsive to chemotherapy; an additional six patients with residual mass underwent surgical resection and were rendered disease-free by surgery. The 5-year actuarial event-free and overall survival were 63.4 and 71.3%, respectively. Conclusions The outcomes of our patients with extragonadal primaries including mediastinal localization appear to be slightly better than those previously reported. Multimodality therapy is essential for these patients and given the relatively poor prognosis, prospective trials with large sample sizes, and new treatment approaches to improve outcome are required. Med Pediatr Oncol 2003;41:49,53. © 2003 Wiley-Liss, Inc. [source] MGEA5 -14 polymorphism and type 2 diabetes in Mexico CityAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 4 2007E. A. Cameron A family-based study has recently reported that a variant located in intron 10 of the gene MGEA5 increases susceptibility to Type 2 Diabetes (T2D). We evaluated the distribution of this SNP in a sample of T2D patients (N = 271) and controls (N = 244) from Mexico City. The frequency of the T allele was higher in the cases (2.6%) than in the controls (1.8%). After adjusting for age, sex, BMI, education, and individual ancestry the odds ratio was 1.60 but the 95% confidence interval was wide and overlapped 1 (0.52,4.86, P -value : 0.404). In order to characterize the distribution of the MGEA5 -14 polymorphism in the relevant parental populations, we genotyped this variant in European (and European Americans), West African, and Native American samples. The T-allele was present at a frequency of 2.3% in Spain, 4.2% in European Americans, and 13% in Western Africans, but was absent in two Native American samples from Mexico and Peru. Given the low frequency of the T-allele, further studies using large sample sizes will be required to confirm the role of this variant in T2D. Am. J. Hum. Biol. 19:593,596, 2007. © 2007Wiley-Liss, Inc. [source] MOMENTUM: DOES THE DATABASE MAKE A DIFFERENCE?THE JOURNAL OF FINANCIAL RESEARCH, Issue 4 2006Bidisha Chakrabarty Abstract We examine discrepancies between the Center for Research in Security Prices (CRSP) and Trade and Quote (TAQ) databases by examining the returns of momentum strategies using each database. Momentum portfolios constructed from CRSP prices earn significant profits whereas similar portfolios using TAQ prices show losses. Adjusting TAQ prices with the TAQ dividends file or with the cumulative distribution factor provided by CRSP does not eliminate all differences. There are significant discrepancies in the way CRSP and TAQ record newly listed and delisted stocks. We document the residual (after all filters) price differences between the two databases and provide filters to adjust TAQ data for long sample periods and large sample sizes. Our filtering procedures allow for the possibility of examining intraday patterns in momentum profits. [source] Evaluation of factors affecting individual assignment precision using microsatellite data from horse breeds and simulated breed crossesANIMAL GENETICS, Issue 4 2002G. Bjørnstad Assignment tests have been utilized to investigate population classification, measure genetic diversity and to solve forensic questions. Using microsatellite data from 26 loci genotyped in eight horse breeds we examined how population differentiation, number of scored loci, number of scored animals per breed and loci variability affected individual assignment precision applying log likelihood methods. We found that both genetic differentiation and number of scored loci were highly important for recognizing the breed of origin. When comparing two and two breeds, a proportion of 95% of the most differentiated breeds (0.200 , FST , 0.259) could be identified scoring only three loci, while the corresponding number was six for the least differentiated breeds (0.080 , FST , 0.139). An identical proportion of simulated breed crosses, differentiated from their parental breeds by FST estimates in the range 0.050,0.069, was identified when scoring 12 loci. This level of source identification was not obtained for the less differentiated breed crosses. The current data further suggested that population sample size and locus variability were not critical for the assignment precision as long as moderately large sample sizes (, 20 animals per population) and fairly variable loci were used. [source] | ||||||||||||||||||||||||||||||||||