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PubMed2000

Ethanol exposure enhances apoptosis within the testes.

BACKGROUND: Chronic ethanol abuse causes testicular atrophy and male infertility in alcoholic men. It is well known that ethanol exposure disrupts the hypothalamic-pituitary-gonadal axis, adversely affects the secretory function of Sertoli cells, and produces oxidative stress within the testes. It is still not clear what cellular mechanisms are responsible for the morphologic alteration of the testes that results in a reduction of testicular mass as a consequence of ethanol exposure. The hypothesis tested was that ethanol enhances apoptosis of testicular germ cells. METHODS: In the experiments of chronic ethanol exposure, male Sprague Dawley rats (Harlan Sprague Dawley, Inc., Indianapolis, IN) were fed Liber-Decarlie liquid diet for 9 weeks. In the experiments of acute ethanol exposure, a small volume of 20% ethanol solution was administered by intratesticular injection. Both 3'-end labeling of isolated testicular deoxyribonucleic acid (DNA) and labeling of apoptotic cells in situ by the terminal deoxynucleotidyl transferase-mediated deoxyuridine 5'-triphosphate nick end-labeling method were used to determine apoptosis rates within the testes. The expression of proteins involved in apoptosis was assessed by reverse transcription-polymerase chain reaction and by Western blotting. RESULTS: The testes of rats that were fed an ethanol-containing liquid diet had more testicular DNA fragmentation than did those of animals that were fed an isocaloric control diet. Ethanol increased the number of apoptotic spermatogonia as well as spermatocytes. Direct intratesticular injections of ethanol solution enhanced testicular DNA fragmentation, suggesting an increase in apoptosis. Moreover, Fas ligand levels were increased within the testes of rats that were chronically fed ethanol. In vitro, ethanol treatment of cultured Sertoli cells enhanced the production of Fas ligand. In addition, testicular levels of p53 messenger ribonucleic acid were increased in rats that were chronically fed ethanol. CONCLUSIONS: All of these observations suggest that ethanol enhances testicular germ cell apoptosis.

Animals↗
PubMed2001

Misconceptions and misuse of the MMPI-2 in assessing personal injury claimants.

The MMPI-2 enjoys widespread popularity in the psychological assessment of personal injury claimants, in part due to its long history, massive research literature, strong empirical basis, and the availability of commercial interpretative and scoring services. However, the relative paucity of studies examining the forensic role of the MMPI-2, raises concerns about the applicability of traditional interpretative guidelines in the medicolegal arena. This paper analyses MMPI-2 protocols of 2080 cases derived from a forensic psychiatric practice in Brisbane, Australia. The data presented here challenges these traditional MMPI-2 interpretations and calls into question assumptions and commonly employed techniques when applied in this setting. In particular, the validity of codetype-based interpretations, the role the MMPI-2 plays in differential diagnosis, and assumptions regarding diagnostically-specific patterns on the test are challenged. MMPI-2 interpretative cookbooks, computer report-writers, adherence to the intent of the test-developers, and appeals to authority are inadequate substitutes for empirical accuracy, and an active hypothesis-testing interpretative approach, based upon setting-specific base-rate data, is recommended.

Attitude of Health Personnel↗
PubMed1986

The assessment of health policy changes using the time-reversed crossover design.

The time-reversed crossover design is a quasi-experimental design which can be applied to evaluate the impact of a change in health policy on a large population. This design makes use of separate sampling and analysis strategies to improve the validity of conclusions drawn from such an evaluation. The properties of the time-reversed crossover design are presented including the use of stratification on outcome in the sampling stage, which is intended to improve external validity. It is demonstrated that, although this feature of the design introduces internal validity threats due to regression toward the mean in extreme-outcome strata, these effects can be measured and eliminated from the test of significance of treatment effects. Methods for within- and across-stratum estimation and hypothesis-testing are presented which are similar to those which have been developed for the traditional two-period crossover design widely used in clinical trials. The procedures are illustrated using data derived from a study conducted by the United Mine Workers of America Health and Retirement Funds to measure the impact of cost-sharing on health care utilization among members of its health plan.

Costs and Cost Analysis↗
PubMedDate not supplied

An application of the health belief model to patient education and compliance: acute otitis media.

This study made use of concepts from the health belief model to test the influence of educational intervention on patient attitude and subsequent sick-role behavior. The hypothesis tested was as follows: Mothers of pediatric patients in an experimental group (N-29) receiving specially designed education about otitis media, would consequently acquire greater awareness of their children's susceptibility to the disease, the possibility of its serious effects, and the benefits of treatment than a comparable control group (N-30) not receiving the educational intervention. It was further hypothesized that patient compliance would be higher in the experimental group. Experimental group health beliefs changed in a significant, positive direction with respect to illness susceptibility and severity, the benefits of treatment, and patient modifying factors. Control group attitudes did not significantly change. Compliance rates for both groups were very high; 91.8% compliance was noted for experimental subjects and 85.6% for controls. This may reflect the additional time and attention given all those participating in the study.

Acute Disease↗
PubMed1997

Application of the learning vector quantizer to the classification of breast lesions.

OBJECTIVE: To investigate the potential of the learning vector quantization (LVQ) neural network for the discrimination of benign from malignant breast lesions. STUDY DESIGN: Using a custom image analysis system on Giemsa-stained smears, 25 parameters describing the size, shape and texture of the cell nucleus were measured. Three thousand nuclei from a total of 9,356 were selected as a training set for the neural network, and the whole data set was used for testing. An additional 238 cells from 16 cases without final cytologic diagnoses were evaluated by the system. The total number of cells (9,594) was collected from 100 patients (68 carcinomas and 32 benign lesions). RESULTS: Cytologic examination of the cases gave two false positive and two false negative results. However, in eight cases of ductal breast carcinoma and in eight cases of benign lesions, histologic confirmation was necessary in order to confirm the cytologic diagnosis. Application of the LVQ permitted correct classification of 87.41% of the cells. Classification at the patient level by using a hypothesis test for proportion with a hypothesis value equal to 50% permitted the correct diagnosis in 98% of patients. CONCLUSION: These results indicate that the use of neural networks combined with image morphometry and statistical techniques may offer useful information about the potential for malignancy, improving the diagnostic accuracy of fine needle aspiration of breast lesions.

Breast↗
PubMed1974

Heavy water slows the Gonyaulax clock: a test of the hypothesis that D2O affects circadian oscillations by diminishing the apparent temperature.

In order to test the hypothesis that deuterium oxide acts in circadian systems by simulating a lower environmental temperature, we have examined the effects of D(2)O on Gonyaulax polyedra, where the period of the circadian rhythm of bioluminescent glow in constant environmental conditions is shorter at 16 degrees than at 22 degrees , and the phase of the glow peak relative to a light-dark cycle is advanced at 16 degrees relative to 22 degrees . Addition of low concentrations of D(2)O to Gonyaulax does not produce the same effects on period and phase as lowering the temperature; the free running period is lengthened and the phase is delayed. These results show that in the Gonyaulax rhythm, the effect of added D(2)O is not equivalent to lowering the temperature.

Animals↗
PubMed1997

Cellular content and permeability of intraluminal thrombus in abdominal aortic aneurysm.

PURPOSE: A pathologic feature commonly associated with abdominal aortic aneurysms is the presence of variably sized and shaped intraluminal thrombus, which may be fundamental to the disease process. However, the precise role of the intraluminal thrombus in the formation, enlargement, and rupture of abdominal aortic aneurysms is unknown. The hypothesis tested in this study was whether there were structural features of aortic thrombi to suggest that it may be involved in the pathogenesis of abdominal aortic aneurysms. We have investigated this hypothesis using a variety of structural and biochemical techniques. METHODS: Tests performed were light, transmission, and scanning electron microscopy; fluid permeability measurements; and Western blots. RESULTS: Intraluminal thrombus found in abdominal aortic aneurysms is structurally complex and is traversed from the luminal to abluminal surface by a continuous network of interconnected canaliculi. Quantitative microscopic analysis of the thrombus shows cellular penetration for at least 1 cm from the luminal surface of the thrombus. Macro-molecular penetration may be unrestricted throughout the entire thickness of the thrombus. Fibrin deposition occurred throughout the thrombus, whereas fibrin degradation occurred principally at the abluminal surface. CONCLUSIONS: These principally structural studies support the hypothesis that the thrombus is a self-sustaining entity that may have significance in the pathophysiologic mechanism of abdominal aortic aneurysms.

Aorta, Abdominal↗
PubMed1995

Resting membrane potentials: a student test of alternate hypotheses.

The frog sartorius muscle is a model tissue for demonstrating to physiology students the principles underlying both membrane phenomena and hypothesis testing. Myocytes can be impaled with conventional glass microelectrodes to measure membrane voltage (Vm). Further, Vm is observed as extracellular K+ is altered and a K+ channel blocker is added. After the experiment, students examine the underlying assumptions of the Nernst equilibrium and the Goldman-Hodgkin-Katz equation. They ultimately determine which of the two algorithms best predicts the measured Vm. In addition, students learn micromanipulation and impalement techniques. This experiment facilitates the student's understanding of membrane permeability, ionic gradients, and membrane voltage.

Algorithms↗
PubMed1987

A Bayesian approach to the multiplicity problem for significance testing with binomial data.

Statistical analyses of simple tumor rates from an animal experiment with one control and one treated group typically consist of hypothesis testing of many 2 X 2 tables, one for each tumor type or site. The multiplicity of significance tests may cause excessive overall false-positive rates. This paper presents a Bayesian approach to the problem of multiple significance testing. We develop a normal logistic model that accommodates the incidences of all tumor types or sites observed in the current experiment simultaneously as well as their historical control incidences. Exchangeable normal priors are assumed for certain linear terms in the model. Posterior means, standard deviations, and Bayesian P-values are computed for an average treatment effect as well as for the effects on individual tumor types or sites. Model assumptions are checked using probability plots and the sensitivity of the parameter estimates to alternative priors is studied. The method is illustrated using tumor data from a chronic animal experiment.

Analysis of Variance↗
PubMed1987

An interactive computer program for the analysis of growth curves.

An interactive FORTRAN program, MUDIFT, is presented. This program was designed to perform a multivariate distribution-free significance test for the comparison of growth curves. Such a test, not assuming functional forms of individual growth, has proved useful when the variety of observed growth curves was too broad to be represented by the family of growth functions and when there were incomplete observations. A numerical example illustrates the use of MUDIFT to analyze serial data pertaining to the measurable solid tumors in 20 mice treated with liposome incorporated muramyltripeptide phosphatidylethanolamine and a control group of 30 mice. The tumor volumes were recorded weekly for 10 weeks following initial entry into the research protocol. The test hypothesis was whether the tumors grew slower in the treated group than in the control group. The test statistic, an asympotically chi 2 statistic, was 7.312 with df = 2, which was significant at alpha = 0.05.

Animals↗
PubMed2005

Analysis of potential lubricants for in vitro wear testing.

OBJECTIVES: A critical testing aspect for a reliable two-body wear simulation may be the lubricity condition. The main hypothesis tested in this study was that, over the experiment duration, the presence or absence of lubricants would provide to a composite similar wear rates to those observed under human saliva lubrication. METHODS: Seventy specimens, fabricated from a minifill composite, were tested in a programmable logic controlled wear simulator with human saliva (HS), mucin-based artificial saliva (MC), carboxymethylcellulose-containing saliva (CM), deionized water (DW) or with no lubrication (UN). Wear depth was quantified at the end of 1000, 5000, 10,000 and 50,000 cycles and at each 50,000 through 250,000 cycles. RESULTS: Over all the test period, UN led to the greatest wear. Initially, lubrication resulted in no significant differences among the wear rates. Subsequently, up to 50,000 cycles, depths of wear provided by HS and MC were still similar, being the lowest, whereas DW yielded greater wear than CM. Later, interposition of CM and HS resulted in equivalent wear. At 250,000 cycles, wear of the composite ranked as follows: MC<HS<CM<DW<UN. Regression analyses showed that for all lubricity conditions wear of the composite rose logarithmically with number of cycles. SIGNIFICANCE: The role of the interposed lubricant was of importance for the wear testing. The present findings supported by studies on the lubricity ability of mucin-based artificial saliva, allowed to conclude that this preparation may be considered as a potential lubricant for in vitro wear test purposes.

Adult↗
PubMed1990

Statistics: curse of the writing class.

Research projects and reports may fail because of investigators' misunderstandings about the principles underlying basic data analysis. Such errors may taint otherwise valid conclusions; related mistakes may serve to falsely support incorrect results. This article explains some of the principles underlying the use of statistical analysis for normally distributed interval data and explores the potential ramifications of misusing summary statistical tests on non-normal distributions. A discussion of the meaning of the statement of probability concerning hypothesis testing and a suggested attitude for researchers toward significance testing is also included.

Data Interpretation, Statistical↗
PubMed2005

A comparison of multiplicity adjustment strategies for correlated binary endpoints.

Several Bonferroni-type adjustments have been proposed to control for family wise type I error among multiple tests. However, many of the approaches disregard the correlation among endpoints. This can result in a conservative hypothesis testing strategy. The James procedure is an alternative approach that accounts for multiplicity among correlated continuous endpoints. Here a simulation study compares four Bonferroni-type alpha-adjustments (Bonferroni, Dunn-Sidák, Holm, and Hochberg) and the James p-value adjustment when used for multiple correlated binary variables. These procedures provided adequate protection against familywise type I error for correlated binary endpoints, albeit, at times, in an overly cautious manner. That is, when correlations among endpoints exceed 0.60, the result is somewhat conservative for the approaches that do not account for those correlations. Among the adjustments examined, the James approach appears to be the uniformly preferred method. Analyses of data from a randomized controlled clinical trial of treatments for mania in bipolar disorder are used to illustrate the application of the multiplicity adjustments.

Antipsychotic Agents↗
PubMed2004

How special is a 'special' interval: modeling departure from length-biased sampling in renewal processes.

Length-biased sampling occurs in renewal processes when the probability that an interval is selected is proportional to the length of the interval. This can occur when intervals are selected because they contain an event that is independent of the renewal process and occurs with constant hazard. For example, if the times between donations for repeat blood donors are independent and identically distributed, and if the donor seroconverts to HIV (develops antibodies that indicate infection with human immunodeficiency virus), then the interval between the last HIV seronegative and first HIV seropositive test is expected to be longer than that donor's previous time intervals between donations. We develop hypothesis tests to determine if the relationship between the typical and length-biased intervals is as expected, or if there is departure from length-biased sampling. We further develop a regression method to determine if there are covariates that explain the departure from length-biased sampling. Our approach is motivated by the question of whether there is evidence that repeat blood donors who develop antibodies to HIV or other viral infections change their donation pattern in some way because of seroconversion.

Blood Donors↗
PubMed2006

Quadratic inference functions for varying-coefficient models with longitudinal data.

Nonparametric smoothing methods are used to model longitudinal data, but the challenge remains to incorporate correlation into nonparametric estimation procedures. In this article, we propose an efficient estimation procedure for varying-coefficient models for longitudinal data. The proposed procedure can easily take into account correlation within subjects and deal directly with both continuous and discrete response longitudinal data under the framework of generalized linear models. The proposed approach yields a more efficient estimator than the generalized estimation equation approach when the working correlation is misspecified. For varying-coefficient models, it is often of interest to test whether coefficient functions are time varying or time invariant. We propose a unified and efficient nonparametric hypothesis testing procedure, and further demonstrate that the resulting test statistics have an asymptotic chi-squared distribution. In addition, the goodness-of-fit test is applied to test whether the model assumption is satisfied. The corresponding test is also useful for choosing basis functions and the number of knots for regression spline models in conjunction with the model selection criterion. We evaluate the finite sample performance of the proposed procedures with Monte Carlo simulation studies. The proposed methodology is illustrated by the analysis of an acquired immune deficiency syndrome (AIDS) data set.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Effect of static pressure on acoustic transmittance of Albunex microbubble suspensions.

Albunex (ALX), an albumin-stabilized microbubble echo contrast agent, is sensitive to pressures similar to those produced by the heart. The tested hypothesis was that the acoustic transmittance of ALX suspensions will increase with increasing hydrostatic pressure (Ps). The test involved an acoustic setup analogous to a spectrophotometer. The acoustic transmittance of microbubble suspensions was strongly Ps dependent. Transmittance at 1 MHz was essentially zero at ambient pressure, increasing to approximately 50%, approximately 63%, and nearly 100% at Ps of 80, 120, and 400 mm Hg, respectively. The ultrasound pulses used to interrogate samples were without measurable effect on the acoustic transmittance of suspensions maintained at ambient pressure during experimental measurements. The data indicate that many of the microbubbles are destroyed at Ps comparable to those produced by the heart.

Acoustics↗
PubMed2000

[A preliminary meta-analysis of 36 studies on impairment of intelligence development induced by iodine deficiency].

OBJECTIVES: Since 1980 s', numerous studies on intelligence quotient (IQ) have documented, in the areas prevalent with severe, moderate and even mild iodine deficiency, which is a risk factor for retardation in mental development there. It was purposed for this paper to quantify the relationship between iodine deficiency and mental development in children and to explore the etiological role of iodine deficiency in mental retardation and the protective effects on children's intelligence of iodine supplementation. METHODS: A total of 59 independent investigations published during 1980 and 1998 were selected for meta-analysis, including 20 studies on intelligence determined by Raven's Test and 39 by China Benit Scale. RESULTS: Homogeneity test showed that there was no significant difference in baseline features between two groups (P > 0.05). The hypothesis testing showed that the homogeneity of each study group was obviously statistically significant (P > 0.05). The results demonstrated that IQ in children at risk for iodine deficiency showed a marked drop by 8.94 points with Raven's Test and by 10.80 points with China Binet Scale, respectively, with an average drop of 10 points. Substantial evidence now available has showed that mental retardation can be prevented by effective correction of iodine deficiency through iodine supplement either iodized salt or iodized oil, which is confirmed by an obvious increase in 11.5 points of IQ in average, and in 11.85 by Raven's Test and 11.64 by China Binet Scale, respectively. CONCLUSIONS: Iodine nutrition plays an important and positive role in brain development. Iodine deficiency leads to loss of 10 points of IQ and 11.5 points can be gained for children in the iodine deficiency areas after significant iodine supplement.

Adolescent↗
PubMed2004

The Precautionary Principle and statistical approaches to uncertainty.

The central challenge from the Precautionary Principle to statistical methodology is to help delineate (preferably quantitatively) the possibility that some exposure is hazardous, even in cases where this is not established beyond reasonable doubt. The classical approach to hypothesis testing is unhelpful, because lack of significance can be due either to uninformative data or to genuine lack of effect (the Type II error problem). Its inversion, bioequivalence testing, might sometimes be a model for the Precautionary Principle in its ability to "prove the null hypothesis". Current procedures for setting safe exposure levels are essentially derived from these classical statistical ideas, and we outline how uncertainties in the exposure and response measurements affect the no observed adverse effect level, the Benchmark approach and the "Hockey Stick" model. A particular problem concerns model uncertainty: usually these procedures assume that the class of models describing dose/response is known with certainty; this assumption is, however, often violated, perhaps particularly often when epidemiological data form the source of the risk assessment, and regulatory authorities have occasionally resorted to some average based on competing models. The recent methodology of the Bayesian model averaging might be a systematic version of this, but is this an arena for the Precautionary Principle to come into play?

Bayes Theorem↗