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PubMed2004

Assessing interaction in case-control studies: type I errors when using both additive and multiplicative scales.

Epidemiologic researchers often explore effect modification in case-control studies on more than one statistical scale, an approach that one expects would increase the rate of false-positive findings of interaction. For example, researchers have measured effect modification by using both a multiplicative interaction coefficient (M) in a logistic regression model and a measure of interaction on the additive scale such as the interaction coefficient from an additive relative risk regression model (A). We performed computer simulations to investigate the degree to which type I error may be inflated when statistical interactions are evaluated by using both M and A. The overall type I error rate was often greater than 5% when both tests were performed together. These results provide empiric evidence of the limited validity of a common approach to assessing etiologic effect modification. When the scale has not been specified before analysis, interaction hypothesis tests of effect modification should be interpreted particularly cautiously. Researchers are not justified in choosing the interaction test with the lowest P value.

Case-Control Studies↗
PubMed1983

Significance testing of many variables. Problems and solutions.

More than one variable of interest in pharmaco-EEG studies is the rule rather than the exception. The many-variables situation may arise from several types of EEG variables and/or from repeated measurements of these variables through time. In many cases, multivariate analysis techniques are not suitable for application. As an alternative, the analyst usually applies individual (univariate) tests for all variables and/or time points. This significance testing of many variables causes problems because of the so-called 'alpha-inflation', i.e. the inflation of the probability for the 'error of the first kind' to reject a null hypothesis although it is valid. To counteract this effect (which invalidates the significance levels used for hypothesis testing), various procedures have been proposed some of which are discussed in the present paper. All procedures involve so-called 'alpha-adjustments', and two procedures are based upon the assumption that the investigator demands that at least a given percentage of all individual null hypotheses considered will be rejected or are not valid, respectively.

Analysis of Variance↗
PubMed2000

Observations in ecology: you can't make progress on processes without understanding the patterns.

Coastal marine ecology is, quite properly, increasingly focussed on experimental tests of hypotheses about processes. These are, however, done to explain observations and patterns. It is therefore appropriate to be able to publish quantitative observations to provide the context and basis for studying mechanisms and processes. Ecologists are concerned about very different types of observations. Some areas of study are still totally dependent on observational, descriptive evidence; some depend on mensurative tests of hypotheses about patterns. Tests of hypotheses about patterns are also needed to validate casual or qualitative observations. Guide-lines for what constitutes appropriate or publishable ecological descriptions are discussed here. These recognize the experimental, hypothesis-testing nature of many descriptive studies and consider the relevance of sound logic and experimental design in the planning, collection and interpretation of observations.

Journal Article↗
PubMed1976

Research strategies for behavioral teratology studies.

Several compelling aruguments have been advanced in support of expanding the use of "behavioral teratology" evaluations as routine components of toxicologic screening procedures. As a basis for development of effective behavioral teratology screening approaches, a conceptual framework is presented which interrelates: (1) changes in relative functional brain capacity with age, (2) possible times and durations of exposures to environmental insults, and (3) various types of toxicity testing procedures carried out at appropriate time points in relation to different exposure period. Within the context, several research strategies for behavioral teratology studies are concisely posed and evaluated. These include: (1) clinical hypothesis testing, where particular effect(s) of a given agent are evaluated based on hypotheses derived from clinical or epidemiological observations; (2) comprehensive screening approaches, where multifaceted, long-term longitudinal neurobehavioral evaluations are employed to assess whether any of a large number of possible deletarious effects are exerted by an agent and at what threshold exposure levels; (3) alternative screening heuristics, by which adequate assessments of neurobehavioral toxicity of various agents may be accomplished without completion of more exhaustive, but also more expensive and time-consuming comprehensive screening protocols.

Aging↗
PubMed2002

Distortion tolerant image recognition receiver by use of a multiple-hypothesis method.

A multiple-hypothesis method is used to detect a target or a reference signal in the presence of additive noise with unknown statistics. The receiver is designed to detect the target and to be tolerant of the variations in rotation and illumination of the target. A multiple-hypothesis test with unknown-noise parameters is used to locate the target position. The proposed method does not use any specific distortion-invariant-filtering technique, but it relies on a multiple-hypothesis approach. Maximum-likelihood estimates of the illumination constant and the unknown noise parameters are obtained. Computer simulations are presented to evaluate the performance of the receiver for various distorted noisy true-class targets with varying illumination and false-class objects.

Journal Article↗
PubMed1991

Chlamydial antigen testing on female patients presenting to the emergency department.

We prospectively determined the prevalence of Chlamydia trachomatis infection in patients presenting to an emergency department over a 4-month period who received pelvic exams. We compared the percentage of cases of Chlamydia diagnosed by the Chlamydiazyme immunoassay with the percentage diagnosed clinically by emergency physicians. Over the study period, 326 pelvic exams were performed. Of 36 patients (11%) with positive tests, 16 (44%) were treated clinically for pelvic inflammatory disease. Twenty (56%) received neither appropriate antibiotic treatment nor a gynecology referral based on clinical exam alone. We statistically evaluated the data using the hypothesis test for two proportions from one group. The difference was significant (Z = 4.6, p less than 0.001).

Adolescent↗
PubMed1997

Predictive patterns of suicidal behavior: the United States armed services versus the civilian population.

Suicide is the eighth leading cause of death in the United States and the third leading cause of death in the military population. The purpose of this study was to compare the suicide rates of the Army, Navy, Marine Corps, and Air Force to the U.S. population for the years 1980 through 1992. Multivariate linear regression analytic techniques were used to test the specific effects of year, service membership, and gender on suicide rates. A hierarchical linear regression equation resulted in R2 = 0.6737, a highly predictive finding (F112,18 = 13.600, p < 0.000). Further controlled hypothesis testing suggested that each independent variable provided a unique contribution to the total variance accounted for in suicide rates. A follow-on set of time series regressions was used to assess the effects of gender and specific military service on suicide rates over the 13-year period. Findings revealed that suicide rates for civilian males are increasing, whereas civilian female rates are declining. No significant trends by year were shown among the services. Military suicide rates were consistently lower than civilian rates, and military female rates tended to be lower yet than military male rates.

Feasibility Studies↗
PubMed2004

Effects of chronic intermittent asphyxia on haematocrit, pulmonary arterial pressure and skeletal muscle structure in rats.

Sleep-disordered breathing in humans is a common condition associated with serious cardiovascular and other abnormalities. The prevalence and pathogenesis of increased haematocrit and pulmonary hypertension is controversial and it has been suggested that these changes only occur in patients who also have daytime continuous hypoxaemia. The hypothesis tested here is that the chronic intermittent hypoxia and asphyxia associated with sleep-disordered breathing causes erythropoiesis and pulmonary hypertension and that this occurs in the absence of periods of continuous hypoxia. In humans and animals with obstructive sleep apnoea, there are abnormalities of upper airway muscle structure that have been ascribed to increased load placed on these muscles. An alternative hypothesis is that chronic intermittent hypoxia and asphyxia cause changes in upper airway muscle structure and function. To test these hypotheses, rats were exposed to intermittent hypoxia and asphyxia for 8 h per day for 5 weeks. This caused an increase in haematocrit, right ventricular weight and pulmonary arterial pressure. There were only slight changes in diaphragm, upper airway and limb muscle structure and force production but in general, muscle fatigability was increased. In conclusion chronic intermittent hypoxia and asphyxia cause an increase in haematocrit and pulmonary arterial pressure in the absence of periods of continuous hypoxia. Chronic intermittent hypoxia and asphyxia have little effect on skeletal muscle structure and force production but increase muscle fatigue. Increased upper airway muscle fatigue could lead to a vicious cycle of further compromise in upper airway patency and further hypoxia and asphyxia.

Animals↗
PubMed2006

Model comparison of generalized linear mixed models.

Generalized linear mixed models (GLMMs) have been widely appreciated in biological and medical research. Maximum likelihood estimation has received a great deal of attention. Comparatively, not much has been done on model comparison or hypotheses testing. In this article, we propose a path sampling procedure to compute the observed-data log-likelihood function, so that the Bayesian information criterion (BIC) can be applied to model comparison or hypothesis testing. Advantages of the proposed path sampling procedure are discussed. Two medical data sets are analysed for providing illustrative examples of the proposed methodology.

Air Pollution↗
PubMed1999

A centrifugal pump driven tidal flow extracorporeal membrane oxygenation system tested with neonatal mock circulation.

In 1993, Chevalier published his experiences with tidal flow venovenous extracorporeal membrane oxygenation (ECMO) featuring a single lumen cannula, non-occlusive roller pump, and alternating clamps. Using a neonatal mock circulation (NMC), which enables different hemodynamic states for neonatal ECMO research, the tested hypothesis was that it is possible to create a centrifugal pump driven tidal flow neonatal venovenous ECMO system. Additionally, the resulting hemodynamic effects in a condition of circulatory impairment were investigated. The ECMO circuit tested was assembled using a pediatric centrifugal pump head, a distensible reservoir, and a rotary clamp separating drainage from the injection phase. Using the NMC, end tidal volumes, mock circulation flow, and arterial and venous pressures were measured at different pump speeds after the drainage and injection phases. Effective venovenous ECMO flow (evvEF) was calculated. Mock circulation baseline values (ECMO clamped) were compared to values during tidal flow ECMO. At 3,000 rpm, a centrifugal pump speed of 75 ml/kg/min evvEF was reached, and it increased with higher pump speeds. At this point, the end tidal mock circulation flow (representing cardiac output) after drainage differed significantly from that during the injection phase (p < 0.01) but not from the baseline value. The end tidal arterial and venous pressures after the drainage phase were found to be significantly decreased compared to the baselines (p < 0.01). In conclusion, a centrifugal pump driven tidal flow venovenous ECMO system can be created enabling sufficient tidal volumes. Tested in the described NMC simulating posthypoxic circulatory impairment, significant hemodynamic effects could be demonstrated. Animal experiments for confirmation are necessary.

Analysis of Variance↗
PubMed2000

Spatial convergence and divergence between cutaneous afferent axons and dorsal horn cells are not constant.

We have proposed a quantitative model of the development of dorsal horn cell receptive fields (RFs) and somatotopic organization (Brown et al. [1997] Somatosens. Motor Res. 14:93-106). One component of that model is a hypothesis that convergence and divergence of connections between low-threshold primary afferent mechanoreceptive axons and dorsal horn cells are invariant over skin location and dorsal horn location. The more limited, and more easily tested, hypothesis that spatial convergence and divergence between cutaneous mechanoreceptors and dorsal horn cell are constant was examined. Spatial divergence is the number of dorsal horn cells whose RFs overlap the RF center of a primary afferent, and spatial convergence is the number of afferent RF centers that lie within the RF of a dorsal horn cell. Innervation density was determined as a function of location on the hindlimb by using peripheral nerve recording and axon counting. A descriptive model of dorsal horn cell receptive fields (Brown et al. [1998] J. Neurophysiol. 31:833-848) was used to simulate RFs of the entire dorsal horn cell population in order to estimate RF area and map scale as a function of location on the hindlimb. Previously reported correlations among innervation density, map scale, and RF size were confirmed. However, these correlations were not linear. The hypothesis that spatial convergence and divergence are constant was rejected. The previously proposed model of development of dorsal horn cell somatotopy and RF geometries must be revised to take variable spatial convergence and divergence into account.

Afferent Pathways↗
PubMedDate not supplied

[Comparing population means using the ANOVA method].

ANOVA is the abbreviation of the ANalysis Of Variance. It was developed for inferences concerning more than two populations. The tested hypothesis is the equality of the means of several normal populations. Some mathematical aspects are presented and also advantages and drawbacks of the method are marked out. Finally a practical example (implementing the ANOVA test) using the SPSS statistical software and also Microsoft Excel are shown.

Algorithms↗
PubMed1995

The prevention of coronary artery aneurysm in Kawasaki disease: a meta-analysis on the efficacy of aspirin and immunoglobulin treatment.

OBJECTIVE: Varying observations have been made concerning the use of aspirin (ASA) and/or intravenous immunoglobulin (IVIG) in the prevention of coronary artery aneurysm (CAA) in children with Kawasaki disease. A meta-analysis of published articles on the subject was conducted to evaluate the reported efficacy of these therapies. METHODS: All published studies in all languages from 1967 through 1993 obtained from MEDLINE and EMBASE were considered, and a defined set of inclusion and exclusion criteria selected the studies for analysis. These studies were grouped based on whether the children in the studies received: (1) ASA alone, (2) low IVIG (< or = 1 g/kg) and ASA, (3) high IVIG (> 1 g/kg) and ASA, (4) single IVIG (> 1 g/kg) and ASA, (5) high IVIG and low ASA (< or = 80 mg/kg), or (6) high IVIG and high ASA (> 80 mg/kg). Studies that satisfied the test for homogeneity were subjected to further analysis. The best estimate of the true proportion of CAA as well as the 95% confidence interval for each group were calculated at 30 and 60 days. Hypothesis testing was conducted to determine the statistical significance of the calculated difference in each compared treatment group. RESULTS: The best estimate of true proportion of CAA and the 95% confidence interval in each group at 30 and 60 days were: (1) ASA group, 30 days, 22.8% (20.6%, 25%); 60 days, 17.1% (13.6%, 20.7%); (2) low-IVIG group, 30 days, 17.3% (14.3%, 20.2%); 60 days, 11.1% (8.7%, 13.6%); (3) high-IVIG group, 30 days, 10.3% (8.3%, 12.3%); 60 days, 4.4% (2.8%, 6%); (4) single-IVIG group, 30 days, 2.3% (0.5%, 4.2%); 60 days, 2.4% (0.5%, 4.2%); (5) high-IVIG-low-ASA group, 30 days, 13% (9%, 17%); 60 days, 4.8% (2.3%, 7.4%); and (6) high-IVIG-high-ASA group, 30 days, 9.1% (6.9%, 11.4%); 60 days, 4% (2%, 6.1%). CONCLUSION: The incidence of CAA both at 30 and 60 days was significantly lower in low-IVIG than in ASA and in high-IVIG than in low-IVIG groups. Also, the incidence was lower in the single-IVIG than in the high-IVIG group, but this was noted at 30 days and not at 60 days. There was no statistically significant difference in the incidence of CAA both at 30 and 60 days between the high-IVIG-low-ASA and high-IVIG-high-ASA groups.

Aspirin↗
PubMedDate not supplied

In defense of proper cosinor analysis.

Parallaxes can originate from different sources, from bias towards proving a favored hypothesis, but also from bias against existing evidence in support of an unwanted hypothesis. One approach to avoiding either bias is to shift emphasis from hypothesis testing to parameter estimation. Complementary statistical approaches applied to replicates of given experiments can then serve to further a given field of science by providing converging or diverging results depending on whether the original hypothesis was true or false.

Acetabularia↗
PubMed2004

Score tests for dose effect in the presence of non-responders.

When only a certain proportion of subjects respond to treatment ('responders') or may never experience an event of interest (thus 'cured'), mixture models often lead to increased understanding of the treatment or disease process. This paper focuses on hypothesis testing in a dose-response framework and shows that increased power is possible by using a mixture model where both the logit of the response rate and the response mean are linear functions of the dose level. Three score tests are developed for testing an overall effect and permutation methods are used to control the type I error. Extensive simulations establish the power properties of the tests and show that our proposed score test has the best performance. The approach is illustrated by a multi-country clinical trial of rapid acting Intramuscular Olanzapine.

Algorithms↗
PubMed1996

Maximum walking speed and lower limb length in hominids.

In 1984, Helene (Am.J. Physics 52:656) and Alexander (Am. Scientist 72:348-354) presented equations which purported to explain how lower limb length limited maximum walking speed in humans. The equations were based on a simplified model of human walking in which the center of mass (CoM) "vaults" over the supporting leg. Increasing walking speed by increasing stride frequency or stride length would increase the upward acceleration of the CoM in the first half of stance phase, to the point that it would be greater than the downward pull of gravity, and the individual would become airborne. This constitutes running by most definitions. While these models ignored various mechanical factors, such as knee flexion during midstance, that reduce the vertical movement of the CoM, the general idea is plausible inasmuch as the CoM of the body does oscillate vertically with each step. One hypothesis tested here is whether it is indeed the interaction between the pull of gravity and the individual's own upward acceleration that determines at what speed (or cadence) he changes from walking to running. Another hypothesis considered is that increased lower limb length (L) was selected for in early hominids, because of the locomotor advantages of longer lower limbs. Results indicate, however, that while L was clearly related to maximum possible walking speed, it was not an important factor in determining maximum "comfortable" walking speed. These and other results from the recent literature suggest that increased lower limb length provided no selective advantage in locomotion, and other explanations should be sought.

Adolescent↗
PubMed2006

Development and testing of the social capital scale for families of children with special health care needs.

The purpose of this study was to develop and psychometrically test the Social Capital Scale for families of children with special health care needs. Researchers have suggested a link between social capital and health, however, psychometrically tested measures of social capital are not described in the literature. The Social Capital Scale (SCS) demonstrated internal consistency, stability over time, and construct validity (as evaluated through factor analysis, correlation with existing measures, and hypothesis testing). Five subscales provide insight into family strengths and areas for improvement related to their investment in relationships that support health. Use of the SCS will contribute to the establishment of consensus and precision in communication about social capital's utility and measurement in the population of families of children with special health care needs.

Adult↗
PubMed2006

LRTae: improving statistical power for genetic association with case/control data when phenotype and/or genotype misclassification errors are present.

BACKGROUND: In the field of statistical genetics, phenotype and genotype misclassification errors can substantially reduce power to detect association with genetic case/control studies. Misclassification also can bias population frequency parameters such as genotype, haplotype, or multi-locus genotype frequencies. These problems are of particular concern in case/control designs because, short of repeated sampling, there is no way to detect misclassification errors. We developed a double-sampling procedure for case/control genetic association using a likelihood ratio test framework. Different approaches have been proposed to deal with misclassification errors. We have chosen the likelihood framework because of the ease with which misclassification probabilities may be incorporated into in the statistical framework and hypothesis testing. The statistic is called the Likelihood Ratio Test allowing for errors (LRTae) and is freely available via software download. RESULTS: We applied our procedure to 10,000 replicates of simulated case/control data in which we introduced phenotype misclassification errors. The phenotype considered is Ankylosing Spondylitis (AS). The LRTae method power was always greater than LRTstd power for the significance levels considered (5%, 1%, 0.1%, 0.01%). Power gains for the LRTae method over the LRTstd method increased as the significance level became more stringent. Multi-locus genotype frequency estimates using LRTae method were more accurate than estimates using LRTstd method. CONCLUSION: The LRTae method can be applied to single-locus genotypes, multi-locus genotypes, or multi-locus haplotypes in a case/control framework and can be more powerful to detect association in case/control studies when both genotype and/or phenotype errors are present. Furthermore, the LRTae method provides asymptotically unbiased estimates of case and control genotype frequencies, as well as estimates of phenotype and/or genotype misclassification rates.

Case-Control Studies↗