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PubMed1996

Pairwise analysis of radiation hybrid mapping data.

Two point lod scores are widely used in pedigree analysis as they provide a fast and efficient method of establishing linkage. Groups of markers that lie in close proximity to one another can be formed by admitting any locus that is linked to at least one existing member of the group with lod score greater than some predetermined value. It seems natural to extend this technique to Radiation Hybrid Mapping both for constructing groups of tightly linked loci that may then be analysed using more powerful statistics and as a method of ordering in its own right. A general extension of two point analysis is derived and the problems associated with radiation hybrid data are discussed. In particular, the additional parameters representing the probabilities of different fragments being retained (which have no parallel in classical linkage analysis) lead to a range of estimators of the breakage probability, O, which have equal and maximal likelihood. Ways of circumventing this problem are discussed along with the potential errors they introduce. Importantly the ambiguity in estimation of theta is not carried through to the lod score as this depends only on the maximum value of the likelihood and not on the particular value of theta at which it occurs. Thus even though two point analysis fails to provide robust estimates of either breakage probabilities or the distance between loci, it represents a simple and effective method of constructing linkage groups that may be analysed with more powerful statistical methods. This is particularly important given the large number of microsatellites, ESTs and candidate genes currently being typed on radiation hybrids.

Chromosome Mapping↗
PubMed2001

Thrombolytic therapy for acute ischemic stroke.

Available evidence of thrombolysis in acute ischemic stroke comes from a series of recent trials conducted in patients with acute stroke, and from a meta-analysis published in the Cochrane Library. The objective of this paper is to review the literature on tolerability and efficacy of thrombolytic therapy in patients with acute ischemic stroke, to find out what the level of evidence is for each thrombolytic drug, and what should consequently be done in the routine practice. This review is based on a bibliographic search of published meta-analyses of randomized trials, published randomized trials, and ongoing randomized trials, with the outcomes of disability, death, and symptomatic intracerebral hemorrhages (fatal or non-fatal). Our primary end-point is a combination of death and disability, in terms of "death or dependency", with dependency defined as a modified Rankin Score (mRS) of >/=3. The level of evidence for the efficacy of a thrombolytic treatment is considered sufficient if there is both a statistically significant effect in the meta-analysis of all randomized trials, without statistically significant heterogeneity, together with one adequately powered and designed conclusive trial. Streptokinase has a clearly harmful effect, without any demonstrated benefit and must not be used in patients with acute ischemic stroke. The level of evidence of an effect of intra-arterial pro-urokinase to reduce death or dependency is low, available data are sparse (only 220 patients), the estimation of its real efficacy and tolerability remains unclear, and its use in clinical practice is not presently justified. The efficacy of alteplase has been incompletely demonstrated because the results vary across trials and type of outcomes (death, death or dependency), and the cut-off of the disability scale. There is a significant heterogeneity in the effect on death or dependency. However, we can conclude that there is a beneficial effect, but its clinical application is limited because of the absence of adequate criteria to identify patients most likely to benefit from treatment. Overall the use of alteplase in patients with acute stroke was associated with some benefit, but it significantly increased total mortality in two trials. Given the observed confidence interval (CI), the results are compatible with, in the best situtation, 203 advoided death or dependency and 61 avoided death per 1000 treated patients, and at worst 77 avoided death or dependency and 38 extra deaths per 1000 treated patients. Further trials aimed at validating more discriminant selection criteria are mandatory.

Acute Disease↗
PubMed2003

Power and measures of effect size in analysis of variance with fixed versus random nested factors.

Ignoring a nested factor can influence the validity of statistical decisions about treatment effectiveness. Previous discussions have centered on consequences of ignoring nested factors versus treating them as random factors on Type I errors and measures of effect size (B. E. Wampold & R. C. Serlin). The authors (a) discuss circumstances under which the treatment of nested provider effects as fixed as opposed to random is appropriate; (b) present 2 formulas for the correct estimation of effect sizes when nested factors are fixed; (c) present the results of Monte Carlo simulations of the consequences of treating providers as fixed versus random on effect size estimates, Type I error rates, and power; and (d) discuss implications of mistaken considerations of provider effects for the study of differential treatment effects in psychotherapy research.

Analysis of Variance↗
PubMed2001

Photodynamic therapy of vulvar intraepithelial neoplasia III using topically applied 5-aminolevulinic acid.

OBJECTIVES: The aim of this study was twofold: first, to determine the feasibility of photodynamic therapy (PDT) of vulvar intraepithelial neoplasia III (VIN III) using topically applied 5-aminolevulinic acid (ALA) for photosensitization, and second, to compare PDT results with those of laser evaporation and local excision. METHODS: Fifteen patients with VIN III had 10 g of 10% ALA gel applied to the entire vulva. Two to three hours after drug application the vulva was irradiated with 120 J/cm(2) laser light at a wavelength of 635 nm. The procedure was performed without anesthesia in most patients. Thirty patients with VIN III treated by laser evaporation and 27 patients treated by surgical excision served as controls. RESULTS: Eight weeks following PDT, 11 of 15 patients were free of VIN III as determined by biopsy. Excellent tissue preservation was achieved and no ulcers or scarring occurred. Three recurrences were seen during follow-up, at 5, 6, and 7 months after PDT. Twelve months after treatment, analysis of disease-free survival revealed no statistically significant difference between patients treated with PDT and patients treated with conventional treatment modalities (P = 0.67) but the power of this analysis is low. In multivariate analysis, multifocal disease was the sole variable associated with a reduced disease-free survival. CONCLUSION: While PDT of VIN III seems to show efficacy similar to that of conventional treatment modalities it offers unique advantages: healing time is short, preservation of normal vulvar appearance is excellent, and PDT may be performed without anesthesia. Hence, PDT of VIN III deserves further investigation.

Administration, Topical↗
PubMed2000

Hyperbaric oxygen increases parasympathetic activity in professional divers.

The role of autonomic nervous system in hyperoxic bradycardia was evaluated by using the power-spectral analysis of heart-rate variability (HRV). Ten professional divers went through two hyperbaric hyperoxic experiments: (1) hyperbaric oxygen (HBO), 100% oxygen at 2.5 ATA, (2) hyperbaric air (HBAIR), O(2) 21% at 2.5 ATA. Four-minute traces of ECG were registered and subjected to power-spectral analysis. Cardiac conduction parameters were evaluated by a diagnostic 12-lead ECG and arrhythmias by a continuous 3-lead ECG. Statistical analysis was made using analysis of variance for repeated measurements. Heart rate decreased (P < 0. 001), but the response was similar during both treatments (P=0.14). Total power increased significantly more during HBO than HBAIR (P=0.003). High-frequency (HF) power (P < 0.001), Hayano's index (P=0.001) and normalized units of HF power (P=0.002) increased and LF/HF index (P < 0.001) decreased more during HBO than HBAIR. There were no changes in cardiac conduction or incidence of arrhythmias. In conclusion, 100% oxygen at 2.5 ATA caused marked increase in parasympathetic tone compared with 21% oxygen at 2.5 ATA.

Analysis of Variance↗
PubMed2003

Multiresolution fMRI activation detection using translation invariant wavelet transform and statistical analysis based on resampling.

A new method is proposed for activation detection in event-related functional magnetic resonance imaging (fMRI). The method is based on the analysis of selected resolution levels (a subspace) in translation invariant wavelet transform (TIWT) domain. Using a priori knowledge about the activation signal and trends, we analyze their power in different resolution levels in TIWT domain and select an optimal set of resolution levels. A randomization-based statistical test is then applied in the wavelet domain for activation detection. This approach suppresses the effects of trends and enhances the detection sensitivity. In addition, since TIWT is insensitive to signal translations, the power analysis is robust with respect to signal shifts. The randomization test alleviates the need for assumptions about fMRI noise. The method has been applied to simulated and experimental fMRI datasets. Comparisons have been made between the results of the proposed method, a similar method in the time domain and the cross-correlation method. The proposed method has shown superior sensitivity compared to the other methods.

Algorithms↗
PubMed1991

The long term prognostic significance of oestrogen receptor analysis in early carcinoma of the breast.

The long term prognostic significance of oestrogen receptors was assessed in a prospective study of 767 patients presenting between the years 1975 and 1981 with stage 1 and 2 breast cancer treated by mastectomy with either full axillary dissection or nodal sampling. Oestrogen receptor binding was determined by a dextran coated charcoal method and median follow up was 11 years. Oestrogen receptors were present in 396 (54%) of tumours. Absence of oestrogen receptors was associated with tumours of high histological grade, but there was no relationship between nodal status or tumour size. Oestrogen receptor status did not predict survival for the group as a whole or when stratified by nodal status. In multivariate analysis both nodal status and tumour size were powerful independent prognostic factors, but oestrogen receptors failed to achieve statistical significance.

Analysis of Variance↗
PubMed2006

Testing differences between nested covariance structure models: Power analysis and null hypotheses.

For comparing nested covariance structure models, the standard procedure is the likelihood ratio test of the difference in fit, where the null hypothesis is that the models fit identically in the population. A procedure for determining statistical power of this test is presented where effect size is based on a specified difference in overall fit of the models. A modification of the standard null hypothesis of zero difference in fit is proposed allowing for testing an interval hypothesis that the difference in fit between models is small, rather than zero. These developments are combined yielding a procedure for estimating power of a test of a null hypothesis of small difference in fit versus an alternative hypothesis of larger difference.

Analysis of Variance↗
PubMed1998

Crossover studies are a better format for comparing equivalent treatments than parallel-group studies.

BACKGROUND: In controlled clinical trials the new treatment may be a slight modification of the standard or be equivalent to it with the addition of a new component. In this situation there is a positive correlation between the response to the new and the standard treatment. OBJECTIVE: The influence of the correlation between the treatment responses on the statistical sensitivity of testing was studied. Randomized trials of equivalent treatments in psychiatry and hypertension research were studied for their design in relation to their level of correlation. RESULTS: With equivalent treatments and, thus, a positive correlation a paired analysis provides better power than an unpaired one. CONCLUSIONS: Crossover studies are a better format than parallel-group studies for comparing equivalent treatments. The scientific community is technically largely unaware of the mechanisms by which correlation levels influence or lack to influence the statistical power of controlled clinical trials.

Adrenergic alpha-Antagonists↗
PubMed2004

Electrogastrography reveals post-prandial gastric dysmotility in children with cystic fibrosis.

OBJECTIVES: Cystic fibrosis patients have a wide spectrum of gastrointestinal disorders. The aim of this study was to investigate the function of gastroenteric neuromusculature and its response to a prokinetic. METHODS: 14 CF children aged 8.6 + 1.3 years were studied by electrogastrography and compared to 10 age-matched controls. A second recording was performed in CF patients after administration of cisapride (0.3 mg/kg). Parameters analyzed were percentage of normal gastric rhythm (2.0 to 4.0 cpm), percentage of tachygastria (4.0 to 9.0 cpm), dominant frequency instability coefficient and power ratio. RESULTS: CF and control groups were not different in age, height or weight. A significant post-prandial increase in percentage of tachygastria (26.7 + 4.5 versus 12.4 + 2.6; P < 0.05) was seen in CF patients, which was not corrected by cisapride. The power ratio showed a statistical increase in 3 cpm (3.7 + 0.8 versus 1.6 + 0.3; P < 0.05) and in tachygastria (5.3 + 1.2 versus 1.7 + 0.4; P < 0.03) in CF compared with controls. Cisapride had an effect on tachygastria power ratio (3.0 + 0.5; P < 0.04). Analysis of normal rhythm and the dominant frequency instability coefficient were not statistically different in CF and controls. CONCLUSION: This study provides evidence of gastric dysmotility in CF patients.

Adolescent↗
PubMed1999

A statistically robust variance-components approach for quantitative trait linkage analysis.

Previously we showed (Wang, Guerra & Cohen 1998) that a statistically robust version of the Haseman & Elston (1972) sib-pair method greatly increased power to detect linkage in the presence of outliers. In this paper we report on M-estimation to accommodate outliers in the variance-components approach to linkage analysis developed by Amos (1994). Simulations show that in the presence of outliers the robust variance-components approach provides substantially greater power, more precise estimation of heritabilities, and better false-positive rates than the original Gaussian based approach. In the absence of outliers the performance of the robust variance-components approach is similar to that of the Gaussian based approach. For illustration we apply the method to two well characterized lipoprotein systems.

Alleles↗
PubMedDate not supplied

Key concepts in biostatistics: using statistics to answer the question "is there a difference?".

Biostatistics seeks to answer the question "Is there a difference?" in the rate of a disease or characteristic among subgroups of patients. The goal of this article is to introduce and define measures used in epidemiology and discuss different types of analyses in clinical research with an emphasis on the concepts and implications of the analyses rather than the mathematics. The implications of the use of measures such as incidence and prevalence, as well as odds, risk, and hazards ratios may affect study conclusions. An understanding of the distinction between these summary measures is essential. The concepts of univariate and multivariate analyses, a discussion of what it means to control for potential confounders, and a description of statistical power and significance are also presented. These concepts are integral to the design and analysis of clinical studies. An understanding of their advantages and applications will enhance the reader's ability to understand and evaluate the literature.

Analysis of Variance↗
PubMed2002

Is esophoria a factor in slowing of myopia by progressive lenses?

PURPOSE: Our previous findings suggest that myopia can be slowed by wearing progressive lenses, and one possible mechanism for this is through the oculomotor system. We reanalyzed our findings to investigate the relationship between baseline oculomotor parameters and change in refraction, and between the change in these values and change in refraction. METHODS: Children who wore progressive lenses (N = 38; 26 with +1.50 D addition, and 16 with +2.00 D addition) or single-vision lenses (N = 32) had refraction, distance heterophoria, near heterophoria, and stimulus AC/A ratio measured prospectively over a 2-year period. RESULTS: There were no statistically significant correlations between baseline heterophoria or AC/A values and change in refractive error. Distance and near heterophoria did not change significantly over the 2 years of the experiment; AC/A ratio decreased significantly, but in an equivalent manner for both groups. In the combined progressive lens group, change toward more exophoria at near was associated with less myopia progression. However three-way analysis of variance (visit x lens type x esophoria/nonesophoria) showed significant main effects in refraction over all five visits. There was a significant interaction between lens type and visits; there was no significant interaction between lens type and esophoria/ nonesophoria grouping. Three-way analysis of variance showed a statistically significant decrease of AC/A ratio over all five visits; there was no interaction of visit by lens or visit by phoria grouping. CONCLUSIONS: Although there were no statistically significant differences between esophoric and nonesophoric subjects, there was only 46% as much myopia progression in the progressive lenses-esophoric group as in the progressive lenses-nonesophoric group. In addition, there were no differences in AC/A ratio between esophoric and nonesophoric subjects. However these findings are not definitive. This experiment was not designed to discriminate between refraction and oculomotor changes in esophoric and nonesophoric subjects and lacked the necessary statistical power to do so.

Analysis of Variance↗
PubMed2004

Prospects for admixture mapping of complex traits.

Admixture mapping extends to human populations the principles that underlie linkage analysis of an experimental cross. For detecting genes that contribute to ethnic variation in disease risk, admixture mapping has greater statistical power than family-linkage studies. In comparison with association studies, admixture mapping requires far fewer markers to search the genome and is less affected by allelic heterogeneity. Statistical-analysis programs for admixture mapping are now available, and a genomewide panel of markers for admixture mapping in populations formed by West African-European admixture has been assembled. Some of the remaining technical challenges include the ability to ensure that the statistical methods are robust and to develop marker panels for other admixed populations. Where admixed populations and panels of markers informative for ancestry are available, admixture mapping can be applied to localize genes that contribute to ethnic variation in any measurable trait.

Black People↗
PubMed1994

Analysis of the wideband external pulse: an application of graphical methods.

This paper demonstrates the power of statistical graphics in gleaning information from very large medical data sets. In the case of the particular data set described here (the wideband external pulse signal) little was known about the shape of the signal and the relationship of that shape to the characteristics of the related physical system, the cardiovascular system. Previous numerical statistical analyses of the data were unfruitful in finding the important relationships which were easily discovered through the appropriately designed graphics. The paper also describes the process of designing graphics to help in discovering the important relationships in the data.

Bias↗
PubMed2005

QSPR modeling of pseudoternary microemulsions formulated employing lecithin surfactants: application of data mining, molecular and statistical modeling.

Data mining, computer aided molecular modeling, descriptor calculation, genetic algorithm and multiple linear regression analysis techniques were combined together to generate predictive quantitative structure property relationship (QSPR) models explaining the formation of lecithin-based W/O microemulsions. Ninety-four microemulsion phase diagrams were collected from five different references published over the past few years. Computer-based molecular modeling techniques were then applied on the components of the collected microemulsion systems to generate corresponding plausible three-dimensional (3D) structures. The resulting 3D models were utilized to calculate a group of molecular physicochemical descriptors. Thereafter, genetic algorithm and backward stepwise regression analysis were separately assessed as means for selecting optimal descriptor sets for statistical modeling. The selected descriptors were correlated with microemulsion existence areas employing multiple linear regression analysis. The resulting W/O models were statistically validated and found to be of significant predictive power. The models allowed better understanding of the process of microemulsion formation. Unfortunately, all QSPR modeling efforts directed towards O/W microemulsions failed completely.

Emulsions↗
PubMed2001

Selected issues in the design and analysis of sport performance research.

The aim of this review is to discuss some issues in the design and statistical analysis of sport performance research, rather than to supply an authoritative 'cookbook' of methods. In general, we try to communicate some possible solutions to the conundrum of how to maintain both internal and external validity, as well as optimize statistical power, in applied sport performance research. We start by arguing that some sport performance research has been overly concerned with physiological predictors of performance, at the expense of not providing a valid and reliable description of the exact nature of the task in question. We show how the influence of certain factors on competitive performances can be described using linear or logistic regression. We discuss the choice of analysis for factorial repeated-measures designs, which is complicated by the assumption of 'sphericity' in a univariate general linear model, and the relatively low statistical power of the multivariate approach when used with small samples. We consider a little-used and simpler technique known as 'analysis of summary statistics'. In multi-group pre- and post-test designs, a useful technique can be to pair-match individuals on their performance scores in a counterbalanced fashion before the intervention or control has been introduced. Finally, we outline how confidence intervals can help in making statements about the probability of the population difference in performance exceeding the value designated as being worthwhile or not.

Humans↗
PubMed1992

Comparison of a two-stage and three-stage interim-analysis procedure.

A statistical model for combining p values from multiple tests of significance is used to define rejection and acceptance regions for two-stage and three-stage sampling plans. Type I error rates, power, frequencies of early termination decisions, and expected sample sizes are compared. Both the two-stage and three-stage procedures provide appropriate protection against Type I errors. The two-stage sampling plan with its single interim analysis entails minimal loss in power and provides substantial reduction in expected sample size as compared with a conventional single end-of-study test of significance for which power is in the adequate range. The three-stage sampling plan with its two interim analyses introduces somewhat greater reduction in power, but it compensates with greater reduction in expected sample size. Either interim-analysis strategy is more efficient than a single end-of-study analysis in terms of power per unit of sample size.

Bias↗