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At least 937 records · Page 52Linked to original sources
PubMed2004

Macrolide therapy for Chlamydia pneumoniae in the secondary prevention of coronary artery disease: a meta-analysis of randomized controlled trials.

STUDY OBJECTIVE: As recent studies have shown that antibiotic therapy to eradicate Chlamydia pneumoniae may be beneficial in the secondary prevention of coronary artery disease, and studies to date may have lacked statistical power, we conducted a meta-analysis of randomized controlled trials to determine the role of antibiotic therapy in this patient population. DESIGN: Systematic review and meta-analysis of randomized controlled trials. PATIENTS: A total of 12,032 patients from nine studies. MEASUREMENTS AND MAIN RESULTS: We searched MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and abstracts of conference proceedings to identify pertinent studies. The random effects model was used to estimate a pooled relative risk. Heterogeneity was assessed using the bootstrap version of the Q statistic with 1000 replications. In total, we reviewed nine randomized controlled trials enrolling 12,032 patients; six enrolled patients with acute coronary syndrome, two enrolled patients with stable coronary artery disease, and one enrolled a mixed population. Compared with placebo, macrolide therapy was not associated with a significant reduction in any coronary event (relative risk [RR] 0.98, 95% confidence interval [CI] 0.88-1.08), myocardial infarction or angina (RR 0.89, 95% CI 0.68-1.16), or overall mortality (RR 0.95, 95% CI 0.81-1.12). CONCLUSION: Our results do not support routine use of antichlamydial therapy for secondary prevention of coronary events.

Antibiotic Prophylaxis↗
PubMed1997

Ethnic-affiliation estimation by use of population-specific DNA markers.

During the past 10 years, DNA analysis has revolutionized the determination of identity in a forensic context. Statements about the biological identity of two human DNA samples now can be made with complete confidence. Although DNA markers are very powerful for distinguishing among individuals, most offer little power to distinguish ethnicity or to support any statement about the physical characteristics of an individual. Through a search of the literature and of unpublished data on allele frequencies we have identified a panel of population-specific genetic markers that enable robust ethnic-affiliation estimation for major U.S. resident populations. In this report, we identify these loci and present their levels of allele-frequency differential between ethnically defined samples, and we demonstrate, using log-likelihood analysis, that this panel of markers provides significant statistical power for ethnic-affiliation estimation. In addition to their use in forensic ethnic-affiliation estimation, population-specific genetic markers are very useful in both population- and individual-level admixture estimation and in mapping genes by use of the linkage disequilibrium created when populations hybridize.

Alleles↗
PubMed2002

On the advantage of haplotype analysis in the presence of multiple disease susceptibility alleles.

We investigated the effect of multiple susceptibility alleles at a single disease locus on the statistical power of a likelihood ratio test to detect association between alleles at a marker locus and a disease phenotype in a case-control design. Using simplifying assumptions to obtain the joint frequency distribution of marker and disease locus alleles, we present numerical results that illustrate the impact of historical variation of initial associations between marker alleles and susceptibility alleles on the power of a likelihood ratio test for association. Our results show that an increase in the number of susceptibility alleles produces a decrease in power of the likelihood ratio test. The decrease in power in the presence of multiple susceptibility alleles, however, is less for markers with multiple alleles than for markers with two alleles. We investigate the implications of this observation for tests of association based on haplotypes made up of tightly linked single-nucleotide polymorphisms (SNPs). Our results suggest that an analysis based on haplotypes can be advantageous over an analysis based on individual SNPs in the presence of multiple susceptibility alleles, particularly when linkage disequilibria between SNPs is weak. The results provide motivation for further development of statistical methods based on haplotypes for assessing the potential for association methods to identify and locate complex disease genes.

Alleles↗
PubMed2006

Effect of spatial smoothing on t-maps: arguments for going back from t-maps to masked contrast images.

Voxelwise statistical analysis has become popular in explorative functional brain mapping with fMRI or PET. Usually, results are presented as voxelwise levels of significance (t-maps), and for clusters that survive correction for multiple testing the coordinates of the maximum t-value are reported. Before calculating a voxelwise statistical test, spatial smoothing is required to achieve a reasonable statistical power. Little attention is being given to the fact that smoothing has a nonlinear effect on the voxel variances and thus the local characteristics of a t-map, which becomes most evident after smoothing over different types of tissue. We investigated the related artifacts, for example, white matter peaks whose position depend on the relative variance (variance over contrast) of the surrounding regions, and suggest improving spatial precision with 'masked contrast images': color-codes are attributed to the voxelwise contrast, and significant clusters (e.g., detected with statistical parametric mapping, SPM) are enlarged by including contiguous pixels with a contrast above the mean contrast in the original cluster, provided they satisfy P < 0.05. The potential benefit is demonstrated with simulations and data from a [11C]Carfentanil PET study. We conclude that spatial smoothing may lead to critical, sometimes-counterintuitive artifacts in t-maps, especially in subcortical brain regions. If significant clusters are detected, for example, with SPM, the suggested method is one way to improve spatial precision and may give the investigator a more direct sense of the underlying data. Its simplicity and the fact that no further assumptions are needed make it a useful complement for standard methods of statistical mapping.

Algorithms↗
PubMed2002

Haplotype block structure and its applications to association studies: power and study designs.

Recent studies have shown that the human genome has a haplotype block structure, such that it can be divided into discrete blocks of limited haplotype diversity. In each block, a small fraction of single-nucleotide polymorphisms (SNPs), referred to as "tag SNPs," can be used to distinguish a large fraction of the haplotypes. These tag SNPs can potentially be extremely useful for association studies, in that it may not be necessary to genotype all SNPs; however, this depends on how much power is lost. Here we develop a simulation study to quantitatively assess the power loss for a variety of study designs, including case-control designs and case-parental control designs. First, a number of data sets containing case-parental or case-control samples are generated on the basis of a disease model. Second, a small fraction of case and control individuals in each data set are genotyped at all the loci, and a dynamic programming algorithm is used to determine the haplotype blocks and the tag SNPs based on the genotypes of the sampled individuals. Third, the statistical power of tests was evaluated on the basis of three kinds of data: (1) all of the SNPs and the corresponding haplotypes, (2) the tag SNPs and the corresponding haplotypes, and (3) the same number of randomly chosen SNPs as the number of tag SNPs and the corresponding haplotypes. We study the power of different association tests with a variety of disease models and block-partitioning criteria. Our study indicates that the genotyping efforts can be significantly reduced by the tag SNPs, without much loss of power. Depending on the specific haplotype block-partitioning algorithm and the disease model, when the identified tag SNPs are only 25% of all the SNPs, the power is reduced by only 4%, on average, compared with a power loss of approximately 12% when the same number of randomly chosen SNPs is used in a two-locus haplotype analysis. When the identified tag SNPs are approximately 14% of all the SNPs, the power is reduced by approximately 9%, compared with a power loss of approximately 21% when the same number of randomly chosen SNPs is used in a two-locus haplotype analysis. Our study also indicates that haplotype-based analysis can be much more powerful than marker-by-marker analysis.

Algorithms↗
PubMed2005

Assessing the power of tag SNPs in the mapping of quantitative trait loci (QTL) with extremal and random samples.

BACKGROUND: Recent studies have indicated that the human genome could be divided into regions with low haplotype diversity interspersed with regions of high haplotype diversity. In regions of low haplotype diversity, a small fraction of SNPs (tag SNPs) are sufficient to account for most of the haplotype diversity of the human genome. These tag SNPs can be extremely useful for testing the association of a marker locus with a qualitative or quantitative trait locus in that it may not be necessary to genotype all the SNPs. When tag SNPs are used to reduce the genotyping effort in association studies, it is important to know how much power is lost. It is also important to know how much power is gained when tag SNPs instead of the same number of randomly chosen SNPs are used. RESULTS: We design a simulation study to tackle these problems for a variety of quantitative association tests using either case-parent samples or unrelated population samples. First, the samples are generated based on the quantitative trait model with the assumption of either an extremal sampling scheme or a random sampling scheme. Second, a small number of samples are selected to determine the haplotype blocks and the tag SNPs. Third, the statistical power of the tests is evaluated using four kinds of data: (1) all the SNPs and the corresponding haplotypes, (2) the tag SNPs and the corresponding haplotypes, (3) the same number of evenly spaced SNPs with minor allele frequency greater than a threshold and the corresponding haplotypes, (4) the same number of randomly chosen SNPs and their corresponding haplotypes. CONCLUSION: Our results suggest that in most situations genotyping efforts can be significantly reduced by using tag SNPs for mapping the QTL in association studies without much loss of power, which is consistent with previous studies on association mapping of qualitative traits. For all situations considered, two-locus haplotype analysis using tag SNPs are more powerful than those using the same number of randomly selected SNPs, but the degree of such power differences depends upon the sampling scheme and the population history.

Chromosome Mapping↗
PubMed2001

Inferring speciation rates from phylogenies.

It is possible to estimate the rate of diversification of clades from phylogenies with a temporal dimension. First, I present several methods for constructing confidence intervals for the speciation rate under the simple assumption of a pure birth process. I discuss the relationships among these methods in the hope of clarifying some fundamental theory in this area. Their performances are compared in a simulation study and one is recommended for use as a result. A variety of other questions that may, in fact, be the questions of primary interest (e.g., Has the rate of cladogenesis been declining?) are then recast as biological variants of the purely statistical question-Is the birth process model appropriate for my data? Seen in this way, a preexisting arsenal of statistical techniques is opened up for use in this area: in particular, techniques developed for the analysis of Poisson processes and the analysis of survival data. These two approaches start from different representations of the data--the branch lengths in the tree--and I explicitly relate the two. Aiming for a synoptic account of useful theory in this area, I briefly discuss some important results from the analysis of two distinct birth-death processes: the one introduced into this area by Hey (1992) is refitted with some powerful statistical tools.

Animals↗
PubMed2004

Serial SimCoal: a population genetics model for data from multiple populations and points in time.

UNLABELLED: We present Serial SimCoal, a program that models population genetic data from multiple time points, as with ancient DNA data. An extension of SIMCOAL, it also allows simultaneous modeling of complex demographic histories, and migration between multiple populations. Further, we incorporate a statistical package to calculate relevant summary statistics, which, for the first time allows users to investigate the statistical power provided by, conduct hypothesis-testing with, and explore sample size limitations of ancient DNA data. AVAILABILITY: Source code and Windows/Mac executables at http://www.stanford.edu/group/hadlylab/ssc.html CONTACT: senka@stanford.edu.

Biological Evolution↗
PubMed1995

Management of localized prostate cancer: an epidemiological perspective.

Prostate cancer is an important and increasing source of male morbidity and mortality. In the absence of any primary preventative strategy, medical approaches to control it will concentrate on attempts at cure in localized disease and effective palliation otherwise. Observational epidemiological studies suggest that, in practice, differences in the effectiveness of aggressive and conservative approaches will be small, but may yet be worthwhile in selected groups of men. However, the confounding and biases inherent in all observational epidemiology mean that the data available from this source is insufficiently certain or precise either to make treatment recommendations for individuals, or to quantify relative benefits to inform health policy. Randomized trial data has not suggested any overwhelming benefit for any one treatment modality, but the five published trials have been small and lacked the statistical power to demonstrate potentially important differences. Aggressive management aimed at cure should be evaluated in adequately designed randomized trials in comparison with expectant medical management ('watchful waiting'). The trials currently planned or under way should be supported enthusiastically by all centres with an interest in management of prostate cancer.

Case-Control Studies↗
PubMed1997

Systematic reviews of medical evidence: the use of meta-analysis in obstetrics and gynecology.

OBJECTIVE: To review the technique of meta-analysis and its uses and limitations in obstetrics and gynecology. DATA SOURCES: We reviewed four major journals in obstetrics and gynecology (American Journal of Obstetrics and Gynecology, Fertility and Sterility, Journal of Reproductive Medicine, and Obstetrics & Gynecology). METHODS OF STUDY SELECTION: Journals were reviewed to determine frequency of meta-analysis as a method of systematic review in obstetrics and gynecology. We also summarized objectives and scientific guidelines for performing a meta-analysis. TABULATION, INTEGRATION, AND RESULTS: Meta-analysis is used with increased frequency in obstetrics and gynecology as a way of systematically reviewing medical evidence. This technique is an attempt to improve on traditional methods of narrative review by an expert and as a framework for evidence-based medicine and developing practice guidelines. By combining data from replicate studies, a meta-analysis can increase statistical power, more precisely estimate the typical effect size of treatment or risk factor, and attempt to resolve controversies in the medical literature. Meta-analysis is a retrospective look at data already collected and is therefore subject to the biases of all retrospective studies. CONCLUSIONS: The technique of meta-analysis requires all the scientific rigor of a randomized clinical trial with careful attention to study design, including a formal protocol for literature search strategies, quality assessment of candidate studies, specific inclusion and exclusion criteria, issues of sampling and publication bias, statistical tests of homogeneity, and sensitivity analysis.

Evidence-Based Medicine↗
PubMed2002

Analysis of comparative data using generalized estimating equations.

It is widely acknowledged that the analysis of comparative data from related species should be performed taking into account their phylogenetic relationships. We introduce a new method, based on the use of generalized estimating equations (GEE), for the analysis of comparative data. The principle is to incorporate, in the modelling process, a correlation matrix that specifies the dependence among observations. This matrix is obtained from the phylogenetic tree of the studied species. Using this approach, a variety of distributions (discrete or continuous) can be analysed using a generalized linear modelling framework, phylogenies with multichotomies can be analysed, and there is no need to estimate ancestral character state. A simulation study showed that the proposed approach has good statistical properties with a type-I error rate close to the nominal 5%, and statistical power to detect correlated evolution between two characters which increases with the strength of the correlation. The proposed approach performs well for the analysis of discrete characters. We illustrate our approach with some data on macro-ecological correlates in birds. Some extensions of the use of GEE are discussed.

Animals↗
PubMed1996

Modeling for intergroup comparisons of imaging data.

Intergroup comparisons pose unique challenges in the analysis of functional imaging data. Imperfections in intersubject stereotaxis can give rise to artifactual results and make it particularly important to allow for intersubject differences in task-related changes when formulating statistical models. Because intergroup comparisons generally involve inferences about the populations from which the subjects were drawn rather than inferences about the particular subjects themselves, subjects must be treated as random rather than fixed effects in the statistical model. These requirements, when combined with the need to adjust for multiple spatial comparisons, result in low statistical power when the number of subjects in each group is small. Functional imaging studies to identify differences between groups generally require many more subjects than other types of functional imaging studies and require careful advance planning to maximize the likelihood of reaching meaningful conclusions.

Brain Mapping↗
PubMed1998

Quantitative trait locus mapping in dairy cattle by means of selective milk DNA pooling using dinucleotide microsatellite markers: analysis of milk protein percentage.

"Selective DNA pooling" accomplishes quantitative trait locus (QTL) mapping through densitometric estimates of marker allele frequencies in pooled DNA samples of phenotypically extreme individuals. With poly(TG) microsatellites, such estimates are confounded by "shadow" ("stutter") bands. A correction procedure was developed on the basis of an observed linear regression between shadow band intensity and allele TG repeat number. Using this procedure, a selective DNA pooling study with respect to milk protein percentage was implemented in Israel-Holstein dairy cattle. Pools were prepared from milk samples of high and low daughters of each of seven sires and genotyped with respect to 11 markers. Highly significant associations with milk protein percentage were found for 5 of the markers; 4 of these markers confirmed previous reports. Selective DNA pooling accessed 80.6 and 48.3%, respectively, of the information that would have been available through individual selective genotyping or total population genotyping. In effect, the statistical power of 45,600 individual genotypings was obtained from 328 pool genotypings. This methodology can make genome-wide mapping of QTL accessible to moderately sized breeding organizations.

Animals↗
PubMed1989

[Methodological consideration on evaluation of lung cancer screening program: one-step process and two-step process].

A reasonable method to evaluate lung cancer screening program is to measure the reduction in death rate from lung cancer among those randomly allocated to screening program (one-step process). Alternative method is two-step process; step 1 is to measure what proportion of lung cancer patients, can be detected through screening and how early the screening can detected lung cancer patients, and step 2 is to delineate effectiveness of therapy following early detection. Advantages and disadvantages of the two processes were described in view of statistical power and sample size. In addition, a workplace-based screening program using chest X-ray files was mentioned as an example of step 1 of two-step process. The example also included economical consideration of the screening.

Adult↗
PubMed2026

Association between the interleukin 17F rs763780 polymorphism and immune thrombocytopenia risk: A systematic review and meta-analysis.

The literature on the Interleukin 17F (IL-17F) rs763780 polymorphism and its association with immune thrombocytopenia (ITP) risk remains inconsistent and controversial. These uncertainties underscore the urgent need for a meta-analysis to objectively synthesize the heterogeneous findings, mitigate bias, and improve statistical power. This study strictly adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and guidelines. A systematic literature search for original studies was conducted across the CNKI, Wanfang Data, Cochrane Library, Web of Science, and PubMed databases, covering publications up to April 5, 2026. Odds ratios and corresponding 95% confidence intervals were calculated to assess the association. STATA 14.2 software was used to synthesize the pooled estimates. A total of eight case-control studies consisting of 805 ITP cases and 841 controls were included. The summarized statistics suggested the detrimental effect of the A allele in the homozygote and recessive models. In the sensitivity analysis, the results that were initially non-significant in the allele, heterozygote, and dominant models became significant after excluding a single dataset, which was also identified as the source of heterogeneity. Region-stratified analyses revealed statistical significance in the Chinese/Japanese and Egyptian subgroups under specific analytic contrasts. When stratified according to age, the children subgroup showed significant associations in a subset of genetic models, while the adult counterpart demonstrated significance across all models. In conclusion, the pooled estimates of the homozygote and recessive models suggested that the rs763780 polymorphism is associated with ITP risk, but this finding requires further validation through large-scale studies.

Humans↗
PubMed2005

The kinetics of the BOLD response depend on inter-stimulus time.

Numerous parameters such as subject age, region of activation, and stimulus timing are known to affect the BOLD signal following neural activation. Here, we investigated how differences in the rest time between successive long visual stimuli alter the kinetics of the BOLD signal in the visual cortex. We found that the BOLD rise time varies with the inter-stimulus interval. By taking this into account when performing statistical analyses of BOLD data, we show that a roughly 20% increase in statistical power can be achieved. In addition, the dependence of the BOLD signal rise time on the inter-stimulus interval provides insight into the physiology underlying the post-stimulus undershoot.

Adult↗
PubMedDate not supplied

Analysis of subjective knee complaints using visual analog scales.

A questionnaire using a system of visual analog scales was developed for analyzing subjective knee complaints. This system was tested on 117 consecutive patients who had undergone knee surgery and 65 patients at their initial office evaluation of a knee disorder. The validity of and patient affinity for this type of questionnaire was compared with that of three other established subjective evaluation methods. The visual analog scale system was shown to be valid and comparable to other methods while offering several advantages. It brought greater sensitivity and greater statistical power to data collection and analysis by allowing a broader range of responses than did traditional categorical responses. It removed bias that was introduced by examiner questioning, and it allowed graphic temporal comparisons. Most importantly, patient affinity was higher for this type of subjective evaluation than for other methods.

Data Interpretation, Statistical↗
PubMed2001

[Sample size and number needed to treat--a statistical case study].

The sample size necessary in each group to detect a significant effect of a vaccine on a given disease in a randomised clinical trial (RCT) can be calculated from the observed disease incidence without vaccine, the expected incidence with vaccine, and the desired level of significance and statistical power of the study. In this example, sample size is calculated for an RCT of the effect of pneumococcal vaccine on the incidence of pneumococcal sepsis. The number of persons needed to be vaccinated to prevent one episode of pneumococcal sepsis can be similarly calculated from the observed incidences with and without vaccine.

Humans↗