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Interpretation of interaction in factorial analysis of variance design.

The validity of statistical conclusions in medical research depends on proper analysis and interpretation of collected data. One potential area of invalidity is the inappropriate post hoc analysis of statistically significant interactions in the analysis of variance of factorial designs. This paper examines the statistical explanations included in 83 studies published in three leading medical journals where the findings indicated significant interaction effects. Only 24 per cent of the reported statistically significant interactions had an accompanying correct interpretation. The most common form of misinterpretation involved a comparison of individual cell means within a row or column of one factor used in the design. This interpretation did not conform to the factorial ANOVA model with interaction. This misinterpretation occurs when the correct omnibus test of a hypothesis is followed by an incorrect post hoc analysis and/or an inaccurate assessment of the original statistical result.

Analysis of Variance↗

An analysis of variance program for the evaluation of results of parallel line assays.

A program is described and illustrated for the one-way analysis of variance of parallel line assays. The procedure involves 4 distinct steps: Data input, either from a previously-prepared data file or by direct 'manual' progression with options to correct input errors; data display, in tabular form, of the results from each specimen after several available transformation options; displays of the analysis of variance table, potency ratio, and confidence limits on the basis of results selected from the data display mode; and, a standard, commercially-available plotting capability of either actual or idealized regression lines. The program provides a rapid, convenient, and accurate procedure, with a high level of operator interaction, with which to perform the somewhat cumbersome mathematical manipulations necessary for the evaluation of parallel line assay results. The availability of this program should overcome one of the problems which frequently prevents the complete analysis and validation of the results of parallel line assays.

Analysis of Variance↗

Variability of midcycle estradiol positive feedback: evidence for unique pituitary responses in individual women.

In women the preovulatory estradiol (E2) level must reach a peak concentration and dose (strength and duration) to initiate the LH surge. The variability of the surge-initiating serum E2 level in individual women from cycle to cycle, however, has not been studied. Accordingly, we studied 24 normally ovulating women longitudinally during a total of 221 menstrual cycles (range, 4-17 cycles/woman). In those women we measured periovulatory serum E2 and LH concentrations daily from 3 days before the LH peak to the day after the LH peak. The mean peak E2 concentration was 343 pg/mL, and the mean E2 dose (concentration X time) was 979 pg/mL. When the values in individual women were compared between women by components of variance analysis of variance, the differences were significant (concentration, P less than 0.01; dose, P less than 0.005), indicating that individual women have discrete and characteristic responses to E2 positive feedback. When E2 peaks and doses from initial cycles were compared with subsequent cycles by regression analysis, there were strong positive correlations (peak: r = 0.47; P less than 0.001; dose: r = 0.60; P less than 0.001). Of the total group variance in mean E2 peak and mean dose, 67% of the peak and 54% of the dose variance resulted from an individual woman's cycle to cycle variability, while 33% of the peak and 46% of the dose variance was attributable to differences among the women's responses to positive feedback. We conclude that individual women have characteristic and predictable periovulatory E2 production, leading to a LH surge which is maintained from cycle to cycle; and approximately two thirds of the total variance in mean peak E2 concentration (67%) and approximately half the variance in mean dose (54%) are the result of cycle to cycle biological variability around this characteristic periovulatory pattern of E2 production.

Adult↗

A new periodogram using one-way analysis of variance for circadian rhythms.

A new periodogram was proposed using one-way analysis of variance (ANOVA), termed ANOVA periodogram, in order to reveal a precise significant periodicity. Thirty 3-day complex computer-simulated time series with known periodicity (24 h) and three 2-h data-missing occurring periodically (23 h, 20 min) were used to compare the ANOVA periodogram with Enright's one. In results, the ANOVA periodogram was superior to Enright's periodogram in the accuracy of assessing the major periodicity.

Algorithms↗

Kruskal-Wallis test: BASIC computer program to perform nonparametric one-way analysis of variance and multiple comparisons on ranks of several independent samples.

Multiple t tests at a fixed p level are frequently used to analyse biomedical data where analysis of variance followed by multiple comparisons or the adjustment of the p values according to Bonferroni would be more appropriate. The Kruskal-Wallis test is a nonparametric 'analysis of variance' which may be used to compare several independent samples. The present program is written in an elementary subset of BASIC and will perform Kruskal-Wallis test followed by multiple comparisons between the groups on practically any computer programmable in BASIC.

Analysis of Variance↗

Misuse of multivariate analysis of variance in behavioral research: the fallacy of the "protected" F test.

Researchers who examine multiple outcome variables sometimes invoke a multivariate analysis of variance approach known as the "protected F test" to control for experimentwise Type I error rate. Unfortunately, this procedure affords protection against experimentwise Type I error only in rare instances. The purpose of the present paper is to present the case against the protected F test and to discuss alternative methods of controlling for Type I error, including the Bonferroni adjustment and descriptive discriminant analysis. The latter approach is briefly elaborated as a truly multivariate solution for multivariate phenomena. The author cites multiple examples of proper and improper use of multivariate analysis of variance in research on child development.

Behavioral Sciences↗

Symmetric differences squared and analysis of variance procedures for estimating genetic and environmental variances and covariances for beef cattle weaning weight: II. Estimates from a data set.

Analysis of variance (ANOVA) and symmetric differences squared (SDS) methods were used to estimate additive genetic and environmental variances and covariances associated with weaning weight. The two methods were applied to 503 beef records collected over 19 yr from a relatively unselected university Angus herd. The SDS methodology was used with four models. The first model included direct (g) and maternal (gm) additive genetic effects, the genetic covariance between direct and maternal additive genetic effects (sigma ggm), permanent maternal environmental effects (m) and temporary environmental effects (e). The second model also allowed for a nonzero environmental covariance (sigma mem) between dam and offspring weaning weights. Models 3 and 4 were models 1 and 2, respectively, expanded to include a grandmaternal genetic effect (gn) and covariances sigma ggn and sigma gmgn. Two ANOVA solution sets for the parameters of model 4 were based on sire, dam, maternal grandsire, maternal grandam and phenotypic variances and offspring-dam (covOD), offspring-sire (covOS), offspring-grandam (covOGD) and offspring-maternal half-aunt or uncle (covOMH) covariances. Four ANOVA solution sets for the parameters of model 2 were based on sire, dam, within dam and maternal grandsire variances, covOD and either covOS or covOGD. Symmetric differences squared estimates of h2g and h2gm averaged .30 and .16, respectively. All SDS estimates of rho ggm (correlation between direct and maternal genetic effects) were less than -1. Estimates of sigma mem were positive. Both SDS estimates and one of the two ANOVA estimates of the grandmaternal variance were negative. The ANOVA model 4 estimates of h2g were .33. The estimates of h2gm were .44 and .39, while the estimates for rho ggm were -.88 and -.80. Both estimates of sigma mem were positive. The four ANOVA model 2 estimates of h2g and h2gm averaged .33 and .48, respectively. Three of the four estimates of rho ggm were less than -.97; the fourth was .35. Three of the four estimates of sigma mem were positive. Expectations show the extent to which SDS and ANOVA estimators were biased by nonzero grandmaternal components that were not accounted for. The extent to which dominance components bias the ANOVA estimators also is shown. Nonzero grandmaternal effects need to be taken into account in either SDS or ANOVA solution sets, or important biases occur with most of the estimators. More numerous, and generally more severe, biases occur with ANOVA estimators than with SDS estimators in solution sets that do not account for grandmaternal effects.

Analysis of Variance↗

Genetics of human body size and shape: body proportions and indices.

BACKGROUND: The study of the genetic component in morphological variables such as body height and weight, head and chest circumference, etc. has a rather long history. However, only a few studies investigated body proportions and configuration. AIM: The major aim of the present study was to evaluate the extent of the possible genetic effects on the inter-individual variation of a number of body configuration indices amenable to clear functional interpretation. SUBJECTS AND METHODS: Two ethnically different pedigree samples were used in the study: (1) Turkmenians (805 individuals) from Central Asia, and (2) Chuvasha (732 individuals) from the Volga riverside, Russian Federation. To achieve the aim of the present study we proposed three new indices, which were subjected to a statistical-genetic analysis using modified version of "FISHER" software. The proposed indices were: (1) an integral index of torso volume (IND#1), an index reflecting a predisposition of body proportions to maintain a balance in a vertical position (IND#2), and an index of skeletal extremities volume (IND#3). Additionally, the first two principal factors (PF1 and PF2) obtained on 19 measurements of body length and breadth were subjected to genetic analysis. Variance decomposition analysis that simultaneously assess the contribution of gender, age, additive genetic effects and effects of environment shared by the nuclear family members, was applied to fit variation of the above three indices, and PF1 and PF2. RESULTS: The raw familial correlation of all study traits and in both samples showed: (1) all marital correlations did not differ significantly from zero; (2) parent-offspring and sibling correlations were all positive and statistically significant. The parameter estimates obtained in variance analyses showed that from 40% to 75% of inter-individual variation of the studied traits (adjusted for age and sex) were attributable to genetic effects. For PF1 and PF2 in both samples, and for IND#2 (in Chuvasha pedigrees), significant common sib environmental effects were also detectable. CONCLUSION: Genetic factors substantially influence inter-individual differences in body shape and configuration in two studied samples. However, further studies are needed to clarify the extent of pleiotropy and epigenetic effects on various facets of the human physique.

Adolescent↗

Overcoming feelings of powerlessness in "aging" researchers: a primer on statistical power in analysis of variance designs.

A general rationale and specific procedures for examining the statistical power characteristics of psychology-of-aging empirical studies are provided. First, 4 basic ingredients of statistical hypothesis testing are reviewed. Then, 2 measures of effect size are introduced (standardized mean differences and the proportion of variation accounted for by the effect of interest), and methods are given for estimating these measures from already-completed studies. Power and sample size formulas, examples, and discussion are provided for common comparison-of-means designs, including independent samples I-factor and factorial analysis of variance (ANOVA) design, analysis of covariance designs, repeated measures (correlated samples) ANOVA designs, and split-plot (combined between- and within-subjects) ANOVA designs. Because of past conceptual differences, special attention is given to the power associated with statistical interactions, and cautions about applying the various procedures are indicated. Illustrative power estimations also are applied to a published study from the literature. It is argued that psychology-of-aging researchers will be both better informed consumers of what they read and more "empowered" with respect to what they research by understanding the important roles played by power and sample size in statistical hypothesis testing.

Aged↗

Microcomputer program for the assessment of one-way, two-way and factorial analysis of variance in pharmaceutical data.

A personal computer program in BASIC for the two-factor factorial analysis of variance has been developed. The factorial design is based on and combined with previous one-way and two-way ANOVA programs. The performance of the program is tested on data obtained from 3 months' consumption of three proprietary antibiotic products in four Saudi hospitals.

Analysis of Variance↗

Hyoid movement during swallowing in older patients with dysphagia.

OBJECTIVES: To describe the timing, coordination, and extent of hyoid movement in a population of older adults with dysphagia and to evaluate the effect of hyoid movement on upper esophageal sphincter opening. DESIGN: A retrospective review of dynamic swallow studies performed between January 1996 and December 1999 was done. SUBJECTS: Patients included in the study were 65 years or older, without an obvious medical or surgical cause for their dysphagia. Timing and distance measures of hyoid movement from the patient population were compared with those from 60 younger (range, 18-62 years) and 23 older (range 67-83 years) control subjects without dysphagia using 1-way analysis of variance. Analysis of the effect of hyoid movement on upper esophageal sphincter opening was performed using contingency tables. RESULTS: In an older population with dysphagia, the coordination of swallowing gestures and bolus timing was intact, hyoid elevation was slow, and the duration of maximal hyoid elevation was reduced, but appropriate for the age of the patients. The hyoid bone elevated farther than normal for small bolus sizes, but the patients were unable to maintain this strategy in larger bolus swallows. CONCLUSION: An increased extent of hyoid displacement in older patients with dysphagia may represent a necessary compensation designed to minimize the effect of the short duration of hyoid elevation on the upper esophageal sphincter opening.

Adolescent↗

A replicate study design for testing bioequivalence: a case study on two desmopressin nasal spray preparations.

OBJECTIVE: The present study was carried out to test bioequivalence between two different desmopressin nasal spray preparations. Due to the high variability of plasma pharmacokinetics of intranasally administered peptides like desmopressin, appropriate study designs are required to assess bioequivalence. Therefore, a single-dose, replicate study design was used to evaluate bioequivalence of two desmopressin nasal sprays. SUBJECTS AND METHODS: Thirty-two healthy male volunteers were enrolled in the study and were randomly assigned to receive the test- and reference drug on two occasions in a 4-period 2-sequence crossover study design. Subjects received a single dose of 20 microg (10 microg per nostril) of desmopressin-acetate per study day separated by wash-out periods of at least 1 week. Desmopressin blood concentrations were measured serially over a 14-h period using a validated radioimmunoassay method. Statistical analysis was initially performed using a complicated mixed-analysis model testing for individual bioequivalence according to recommendations by the Food and Drug Administration. This approach, however, failed to converge with all defined main PK parameters and, thus, a traditional mixed analysis of variance analysis based on population averages was definitely used for testing bioequivalence between study drugs. The procedure of selecting an appropriate statistical analysis for a replicate study design was predefined in the study protocol. RESULTS: The 90% confidence intervals (CI) were calculated for the area under the time-concentration curve (AUC), maximum concentration (C(max)) and the time to reach C(max) (t(max)) of test/reference drug ratios for a bioequivalence range from 0.80-1.25. The mean test/reference drug ratios were completely within the 90% CIs with values of 1.041 (CI: 0.892-1.216), 1.021 (CI: 0.913-1.140) and 1.068 (CI: 0.914-1.249) for AUC(0-14 h), C(max) and t(max), respectively. CONCLUSION: The rate and the extent of intranasal desmopressin absorption are identical for both study preparations. Thus, the desmopressin test preparation met all equivalence criteria and thereby was proven bioequivalent with a marketed reference nasal desmopressin spray.

Administration, Intranasal↗

Development of circadian rhythmicity of temperature in full-term normal infants.

Twelve full-term infants (7 girls and 5 boys) with normal neurological, behavioral and somatic development were followed at regular intervals during the first 5 months of life to appreciate the development of circadian rectal temperature rhythmicity. Activity and temperature (oral at birth, rectal thereafter) were monitored for a minimum of 60 hours on seven separate occasions: at birth, 3 weeks, 6 weeks, 8 weeks, 10 weeks, 16 weeks and 20 weeks of age. Activity was measured using an actigraph worn on the infant's wrist, and rectal temperature was measured using a rectal probe attached to a portable microprocessor (Vitalog TM). Data points were collected every 2 minutes. No fewer than ten infants were monitored at each session, and no infant missed more than one session. Missing recordings were due to equipment malfunctions, probe expulsions and minor health problems. Six infants out of 12 were successfully monitored at each of the first four sessions, from birth to 8 weeks of age inclusively, and two subjects were successfully monitored at all seven sessions. Periodic regression analysis was performed by least squares curve fit with secondary analysis of variance. Analysis of covariance was performed on repeated measures. There was no evidence of rectal temperature circadian rhythmicity at 3 weeks. Two infants demonstrated a circadian rhythmicity at 6 weeks, and all infants had a circadian rhythmicity at 10 weeks post-natal age. At the time of the first observance of circadian rhythmicity of rectal temperature, the mean delta in temperature from peak to trough was 0.6 +/- 0.3 degrees C. This delta was greater at the 16th week, with a mean value of 1.2 +/- 0.3 degrees C. The trough was seen during the first part of the long nocturnal inactivity period. Circadian rhythmicity of rectal temperature was always observed in the studied subjects before the establishment of a consolidated, long daytime wake period.

Body Temperature Regulation↗

Corneal thickness in children.

OBJECTIVE: To determine normal central and paracentral corneal thickness measurements in the pediatric population and to determine if these measurements are consistent across different pediatric age groups and different racial groups. DESIGN: Prospective observational case series. METHODS: Pachymetry measurements were performed on 198 eyes of 108 children. The measurements were taken centrally as well as at four paracentral sites 3 mm from the corneal center at the 3, 6, 9, and 12 o'clock positions. The two-tailed t test was used for comparison of the continuous means for values of corneal thickness. Analysis of variance (ANOVA) was performed to determine differences among age and ethnic groups RESULTS: The mean central corneal thickness (CCT) was 549 +/- 46 microm. Paracentral corneal thickness mean values, as measured 3 mm from the corneal center, were as follows: superior, 575 +/- 52 microm; nasal, 568 +/- 50 microm; inferior, 568 +/- 51 microm; and temporal, 574 +/- 47 microm. The mean CCT values were significantly thinner than at each of the mean paracentral points (P < .05 for each comparison, paired t test). Paracentral corneal thickness measurements demonstrated no significant differences between locations (P > .05, variance analysis). The mean CCT +/- SD for each age group was as follows: 6 to 23 months, 538 +/- 40 microm; 2 to 4 years, 546 +/- 41 microm; 5 to 9 years, 566 +/- 48 microm; and 10 to 18 years, 554 +/- 35 microm (ANOVA P = .012). ANOVA performed on central pachymetry values demonstrated no significant differences among racial subgroups. CONCLUSIONS: Pediatric central and paracentral corneal thicknesses increase slowly over time and reach adult thicknesses at 5 to 9 years of age.

Adolescent↗

Effects of annular size, transmitral pressure, and mitral flow rate on the edge-to-edge repair: an in vitro study.

BACKGROUND: Although edge-to-edge repair is an established adjunctive procedure, there is still debate on its long-term durability and efficacy. METHODS: Fifteen porcine mitral valves were studied in a physiologic left heart simulator with a variable size annulus (dilated = 8.22 cm2, normal = 6.86 cm2, contracted = 5.5 cm2). Mitral valves were tested under steady and physiologic pulsatile flow conditions (cardiac outputs: 4 to 6 L/min), at peak transmitral pressures between 100 mm Hg and 140 mm Hg. A miniature force transducer was used to measure the Alfieri stitch force (F(A)). Mitral flow rate (MFR), transmitral pressure, effective orifice area, mitral regurgitation, and F(A) were monitored. RESULTS: The edge-to-edge repair led to a decrease in effective orifice area of 16.55% +/- 8.22%; further reduction in effective orifice area was attained with annular contraction. Mitral regurgitation after the edge-to-edge repair was significantly higher (p <0.05) with annular dilation. In the pulsatile experiments, two peaks in F(A) were observed: one during systole (F(A) = 0.059 +/- 0.024 N) and a second during diastole (F(A) = 0.072 +/- 0.021 N). Multivariate analysis of variance analysis showed that during systole, transmitral pressure and mitral annular area (MAA) had significant effects on F(A) [F(A) = (4.40 x 10(-4)) transmitral pressure (mm Hg) + (5.0 x 10(-3)) MAA (cm2) - 0.05 (R2 = 0.80)], whereas during diastole MFR and MAA had significant effects on F(A) [F(A) = (1.03 x 10(-4)) MFR2 (L/min) - (1.60 x 10(-3)) MAA (cm2) + 0.02 (R2 = 0.90)]. CONCLUSIONS: With annular dilation, mitral regurgitation persisted even after the edge-to-edge repair. The edge-to-edge repair does not cause clinically relevant mitral valve stenosis in a normal size mitral valve. Mitral flow rate and transmitral pressure are the main determinants of F(A) during the cardiac cycle. Increasing annular area increases F(A) during systole but decreases F(A) during diastole. Systolic F(A) may become dominant with increases in MAA or peak transmitral pressure, or both.

Animals↗

Evaluation of the clinical benefit of permixon and tamsulosin in severe BPH patients-PERMAL study subset analysis.

OBJECTIVE: To compare the efficacy of the lipido-sterolic extract of Serenoa repens, Permixon, to that of the alpha-blocker, tamsulosin, in the treatment of severe low urinary tract symptoms (LUTS) of benign prostatic hyperplasia (BPH). METHODS: In a 12-month, double-blind, randomized study that showed equivalent efficacy of Permixon 320 mg/day and tamsulosin 0.4 mg/day ("PERMAL study"), 685 BPH patients with IPSS > or =10 had been analyzed for efficacy. Of these, the 124 patients with severe LUTS (IPSS >19) at randomization were retained for this subset analysis. After a 4-week run-in period, 59 and 65 patients had been randomized to tamsulosin and Permixon groups, respectively. Both treatment groups were compared regarding the evolution from baseline of total IPSS and its irritative and obstructive subscores, LUTS-related QoL, prostate volume, Q(max) and MSF-4 (sexual activity questionnaire) at different time points over 1 year. An analysis of variance of changes from baseline to end point was performed for all the parameters. The over-time evolutions of total, irritative and obstructive IPSS were further compared using a variance analysis for repeated measurements. RESULTS: At 12 months, total IPSS decreased by 7.8 with Permixon and 5.8 with tamsulosin (p=0.051); the irritative symptoms improved significantly more (p=0.049) with Permixon (-2.9 versus -1.9 with tamsulosin). The superiority of Permixon in reducing irritative symptoms appeared as soon as month 3 and was maintained up to month 12 (p=0.03). CONCLUSION: Permixon 320 mg/day was shown to be slightly superior to tamsulosin 0.4 mg/day in reducing LUTS in severe BPH patients after 3 months and up to 12 months of treatment.

Adrenergic alpha-Antagonists↗

Dietary intake of vitamin D in premenopausal, healthy vegans was insufficient to maintain concentrations of serum 25-hydroxyvitamin D and intact parathyroid hormone within normal ranges during the winter in Finland.

OBJECTIVE: To study vitamin D status and bone metabolism of premenopausal vegetarians and omnivores during a 1-year period. DESIGN: Longitudinal, observational study. Bone mineral density was measured, blood samples from fasting subjects were obtained, and 24-hour urinary samples were collected in February 1994, August 1994, and January 1995. Serum 25-hydroxyvitamin D [S-25(OH)D] and intact parathyroid hormone (S-iPTH) concentrations were measured and intestinal calcium absorption was estimated. Dietary intakes of vitamin D and calcium were calculated. SUBJECTS/SETTING: Six vegans, 6 lactovegetarians, and 16 omnivores living in Helsinki, Finland. STATISTICAL ANALYSES PERFORMED: Student-Newman-Keuls test; unbalanced, repeated-measures multiple analysis of variance; analysis of covariance; Pearson correlation test; and linear regression analysis. RESULTS: Dietary intake of vitamin D was significantly lower in vegans (P < .05, yearly mean +/- standard deviation = 0.09 +/- 0.06 microgram/day) and in lactovegetarians (P < .05, 0.7 +/- 0.4 microgram/day) compared with omnivores (4.0 +/- 2.1 micrograms/day). Throughout the year S-25(OH)D (P = .01) concentrations were lower and S-iPTH (P = .01) concentrations were higher in vegans than in omnivores and lactovegetarians. Bone mineral density in the lumbar region of the spine was lower in vegans (yearly mean +/- standard deviation = 1.034 +/- 0.174 g/cm2) than in omnivores (P = .05, 1.177 +/- 0.099 g/cm2) and tended to be lower than that in lactovegetarians (P = .17, 1.138 +/- 0.06 g/cm2). Bone mineral density in the neck of the femur tended to be lower in vegans (0.843 +/- 0.116 g/cm2) than in omnivores (P = .07, 0.999 +/- 0.138 g/cm2) and lactovegetarians (P = .15, 0.961 +/- 0.059 g/cm2). No seasonal variation was found in bone mineral density in the study groups. CONCLUSIONS: At northern latitudes, dietary intake of vitamin D in vegans was insufficient to maintain S-25(OH)D and S-iPTH concentrations within normal ranges in the winter, which seems to have negative effects on bone mineral density in the long run. APPLICATIONS: An increase in vitamin D intake should generally be recommended for vegans at least during winter, or selections of foodstuffs fortified with vitamin D should be broadened in northern latitudes.

Absorptiometry, Photon↗