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Testing separate families of segregation hypotheses: bootstrap methods.

Aspects of the statistical modeling and assessment of hypotheses concerning quantitative traits in genetics research are discussed. It is suggested that a traditional approach to such modeling and hypothesis testing, whereby competing models are "nested" in an effort to simplify their probabilistic assessment, can be complimented by an alternative statistical paradigm - the separate-families-of-hypotheses approach to segregation analysis. Two bootstrap-based methods are described that allow testing of any two, possibly non-nested, parametric genetic hypotheses. These procedures utilize a strategy in which the unknown distribution of a likelihood ratio-based test statistic is simulated, thereby allowing the estimation of critical values for the test statistic. Though the focus of this paper concerns quantitative traits, the strategies described can be applied to qualitative traits as well. The conceptual advantages and computational ease of these strategies are discussed, and their significance levels and power are examined through Monte Carlo experimentation. It is concluded that the separate-families-of-hypotheses approach, when carried out with the methods described in this paper, not only possesses some favorable statistical properties but also is well suited for genetic segregation analysis.

Alleles↗

Anosognosia for hemiplegia: test of the personal neglect hypothesis.

OBJECTIVE: To test the personal neglect hypothesis of anosognosia for hemiplegia (AHP) using selective anesthesia of the right hemisphere. BACKGROUND: Although AHP most commonly follows right-hemisphere injury, the mechanism responsible for this hemispheric asymmetry has not been entirely elucidated. Because denial of ownership of parts on the contralesional side of one's body (personal neglect) also more commonly follows right-hemisphere damage, personal neglect might account for AHP. DESIGN/METHODS: AHP and personal neglect were assessed in 20 patients during right intracarotid barbiturate infusion. With vision restricted to the central field, patients were randomly presented with either their own hands or those of examiners matched for size, gender, and race. Patients were asked to read numbers placed on the hands to establish that hemianopia did not confound hand recognition. RESULTS: All subjects correctly read the numbers on all trials. Only 4 of 20 subjects misidentified their hands and denied awareness of left hemiplegia. All errors occurred for the left hand, indicating personal neglect. However, the 16 subjects without personal neglect also demonstrated AHP. CONCLUSION: Because AHP and personal neglect are dissociable, personal neglect cannot completely account for AHP.

Adult↗

The persistence of underpowered studies in psychological research: causes, consequences, and remedies.

Underpowered studies persist in the psychological literature. This article examines reasons for their persistence and the effects on efforts to create a cumulative science. The "curse of multiplicities" plays a central role in the presentation. Most psychologists realize that testing multiple hypotheses in a single study affects the Type I error rate, but corresponding implications for power have largely been ignored. The presence of multiple hypothesis tests leads to 3 different conceptualizations of power. Implications of these 3 conceptualizations are discussed from the perspective of the individual researcher and from the perspective of developing a coherent literature. Supplementing significance tests with effect size measures and confidence intervals is shown to address some but not necessarily all problems associated with multiple testing.

Humans↗

Reinforcement without awareness: II. Word class.

In a previous study of reinforcement without awareness by Lieberman, Sunnucks, & Kirk (this issue), subjects were told that the experiment was on ESP; two words were presented on every trial, and their task was to choose the word the experimenter was thinking of. In fact, reinforcement was contingent on the loudness of the subjects' voices when responding. They found stronger evidence for reinforcement without awareness than in many previous studies, and they attributed their success in part to the reinforcement of a response to which subjects were unlikely to attend. To explore this factor further, we again used an ESP cover story but reinforced subjects for choosing the word in each pair that contained a double letter. We found evidence of reinforcement without awareness in three experiments and also identified two factors that influence these effects: Learning did not occur if subjects (a) were encouraged to test irrelevant hypotheses, or (b) sat in an uncomfortable chair. We speculate that learning without awareness may be more likely when subjects are relaxed and that hypothesis testing and uncomfortable chairs impair such learning because they prevent relaxation.

Adult↗

DNA fingerprinting data and the problem of non-independence among pairwise comparisons.

Multilocus DNA fingerprinting is commonly used to assess genetic similarity within and between geographically disjunct populations. Typically, the proportion of DNA fingerprinting bands shared between two individuals (SXY) is calculated for all possible pairwise comparisons and the resulting data analysed parametrically to test differences in mean band-sharing among groups. The degree to which covariation among interdependent SXY values (S(ab)-Sbc) biases the analyses is often unknown. Here, we assess the extent of covariation in four DNA fingerprinting studies and evaluate the effectiveness of two corrective procedures, a permutation test and a subsampling routine using only independent pairwise comparisons drawn without replacement from the overall data. Covariation among interdependent SXY values was significantly greater than zero in every data set examined, including those from a bee, a rodent, and two passerine birds. Permutation tests did not correct for interdependence and yielded significance values nearly identical to those derived from uncorrected parametric procedures. In contrast, the subsampling procedure yielded corrected estimates of the standard error that were two to four times larger than those derived parametrically. As a result, comparisons that were significant using parametric tests were either non-significant or only marginally significant with the subsampling routine. We conclude that interdependence among SXY values poses a substantial obstacle to hypothesis testing that must be addressed in future studies.

Analysis of Variance↗

A conjoint measurement analysis of clinical predictions.

A lack of impressive theories in clinical psychology has been attributed to an excessive reliance on significance testing. Conjoint measurement is a worthwhile alternative to significance testing. Conjoint measurement determines whether data obey the ordinal properties of a model that contains main effect terms, interaction terms, or a combination of the two. Unlike hypothesis testing, with conjoint measurement an increase in statistical power leads to a greater risk of refuting a theory. In this study, conjoint measurement was used to describe how systems-oriented therapists predict the occurrence of suicide. Although the systems approach emphasizes the interaction between an individual and a system, all 10 clinicians were described by an additive model.

Humans↗

Genetic Analysis Workshop II: results of segregation analyses using POINTER and linkage analyses using LIPED.

Genetic Analysis Workshop II Problems 2 and 3 were analyzed using the segregation analysis program, POINTER and the linkage analysis program LIPED. Results of the segregation analyses were acceptable with respect to both parameter estimation and hypothesis testing. Results of the linkage analyses were also good. Although it was noted that the linkage and population association data were sometimes compatible with more than one hypothesis, the correct relationships among the trait and marker loci were generally among those found compatible with the data.

Alleles↗

A simple significance test for quantile regression.

Where OLS regression seeks to model the mean of a random variable as a function of observed variables, quantile regression seeks to model the quantiles of a random variable as functions of observed variables. Tests for the dependence of the quantiles of a random variable upon observed variables have only been developed through the use of computer resampling or based on asymptotic approximations resting on distributional assumptions. We propose an exceedingly simple but heretofore undocumented likelihood ratio test within a logistic regression framework to test the dependence of a quantile of a random variable upon observed variables. Simulated data sets are used to illustrate the rationale, ease, and utility of the hypothesis test. Simulations have been performed over a variety of situations to estimate the type I error rates and statistical power of the procedure. Results from this procedure are compared to (1) previously proposed asymptotic tests for quantile regression and (2) bootstrap techniques commonly used for quantile regression inference. Results show that this less computationally intense method has appropriate type I error control, which is not true for all competing procedures, comparable power to both previously proposed asymptotic tests and bootstrap techniques, and greater computational ease. We illustrate the approach using data from 779 adolescent boys age 12-18 from the Third National Health and Nutrition Examination Survey (NHANES III) to test hypotheses regarding age, ethnicity, and their interaction upon quantiles of waist circumference.

Adolescent↗

The effect of head position, electrode site, movement and smoothing window in the determination of a reliable maximum voluntary activation of the upper trapezius muscle.

Quantitative measures derived from raw myoelectric signal (MES) data must be normalized to allow for comparisons both within and between subjects. The most common method of normalization involves dividing the root mean square (RMS) amplitude of the MES recorded during a given activity by the RMS of the MES elicited during a maximal voluntary isometric contraction (MVIC) of that particular muscle. The objective of this study was to use surface-recorded MES amplitude to determine the combination of electrode site, test position, head posture, and smoothing window that elicits the highest and most reliable MES amplitudes during an MVIC of the upper trapezius (UT) muscle. Ten volunteers had surface electrodes positioned at five sites on the UT of their dominant side. Three trials of each of three MVIC test positions were performed both with the head in neutral and rotated 45 degrees to the contralateral side. A repeated-measures ANOVA was used for statistical hypothesis testing. Coefficients of variation were used to quantify the between-factor variability introduced in each case. In addition, the data were re-analyzed using moving windows of 100 to 500 ms in length, and an ANOVA was used to determine the effect of window length on both the amplitude and variability of the estimates of maximum voluntary activation (MVE). Head position had no significant effect on RMS amplitude of the MVIC in any of the test positions. There was a significant electrode site by test position interaction effect. Bonferroni post-hoc analyses were performed on this interaction by fixing test position and testing electrode site, revealing that Sites 1 (2 cm lateral to the midpoint between C7 spinous process and the posterolateral border of the acromion) and 4 (2 cm posterior to Site 1) recorded significantly higher RMS values for all test positions, and were not significantly different from each other. Fixing electrode site, the test position analysis revealed that abduction of the humerus, and abduction with external rotation of the humerus produced significantly higher RMS values than shoulder elevation at both Sites 1 and 4, and that abduction produced a significantly higher RMS amplitude than abduction in external rotation at Site 1. The results confirmed that Sites 1 and 4 consistently produced the highest MES amplitudes for all movements. Pure abduction consistently elicited maximal RMS values; however there is concern regarding supraspinatus cross talk during this movement. Site 1 was found to produce the most reliable data. A moving window of 100 ms was found to generate MVE estimates that were significantly higher than windows ranging from 200 ms to 500 ms in length. There was no effect of window length on the reliability of the MVEs. Based on this study, it was concluded that abduction or abduction with the arms in lateral rotation should be used as normalization contraction positions for the upper trapezius muscle. During this movement, Site 1 data smoothed with a moving window of 100 ms produces the highest amplitude MVE data but window lengths greater than 200 ms produce more stable estimates in terms of being able to compare studies in which moving windows are used to compute RMS.

Adult↗

Tolerance of an enterally administered simulated amniotic fluid-like solution by neonates recovering from surgery for congenital bowel abnormalities.

OBJECTIVE: We report a single-centered, Phase I pilot trial, testing the enteral administration of an experimental amniotic fluid-like solution to 10 neonates who were otherwise "NPO" following surgery for congenital bowel abnormalities. The overall hypothesis was that the trophic effect of the solution on intestinal villi would facilitate advancement to full enteral feedings. The specific hypothesis tested in this pilot trial was that the solution would be tolerated. STUDY DESIGN: Ten neonates who were NPO following surgery for congenital bowel abnormalities, were studied before any "trophic" feedings were begun. Each received an experimental, sterile, isotonic, amniotic fluid-like solution at a dose of 20 ml/kg/day enterally. When milk feedings were begun they were mixed with the experimental solution. Increases in the volume of milk feedings occurred at the discretion of the neonatologist and surgeon, and the experimental solution was discontinued any time the neonatologist or surgeon felt it was not tolerated, or when 100 ml of milk feedings/kg/day was achieved. We quantified the amount and character of emesis, stools, and gastric residuals, measured abdominal girth and blood pressure, looked for skin rashes, and sought any signs of intolerance or adverse events. We recorded the days to achieve milk feedings of 20, 50, 100, and 120 ml/kg/day and length of hospital stay. RESULTS: The experimental solution was begun 4 to 32 days after surgery, invariably prior to the institution of "trophic" milk feedings. All subjects completed the doses with no evidence of intolerance. All achieved 100 ml/kg of milk feedings 14 days, or fewer, following institution of the experimental solution (mean 11.1 days, range, 3 to 14). All lived and were discharged home 20.2 days (range, 8 to 42) after the experimental solution was begun. CONCLUSIONS: In this pilot trial involving 10 neonates who had surgery for congenital bowel abnormalities, the enteral administration of a sterile, isotonic, amniotic fluid-like solution was tolerated.

Drug Combinations↗

First policy then science: why a management unit based solely on genetic criteria cannot work.

In contrast to the goals of the symposium from which this series of papers originated, we argue that attempts to apply unambiguously defined and general management unit criteria based solely on genetic parameters can easily lead to incorrect management decisions. We maintain that conservation genetics is best served by altering the perspective of data analysis so that decision making is optimally facilitated. To do so requires accounting for policy objectives early in the design and execution of the science. This contrasts with typical hypothesis testing approaches to analysing genetic data for determining population structure, which often aspire to objectivity by considering management objectives only after the analysis is complete. The null hypothesis is generally taken as panmixia with a strong predilection towards avoiding false acceptance of the alternative hypothesis (the existence of population structure). We show by example how defining management units using genetic data and standard scientific analyses that do not consider either the specific management objectives or the anthropogenic risks facing the populations being studied can easily result in a management failure by losing local populations. We then use the same example to show how an 'applied' approach driven by specific objectives and knowledge of abundance and mortality results in appropriate analyses and better decisions. Because management objectives stem from public policy, which differs among countries and among species groups, criteria for defining management units must be specific, not general. Therefore, we conclude that the most productive way to define management units is on a case-by-case basis. We also suggest that creating analytical tools designed specifically to address decision making in a management context, rather than re-tooling academic tools designed for other purposes, will increase and improve the use of genetics in conservation.

Animals↗

The influence of lorazepam upon pre- and poststimulus EEG during sleep in man.

Enhancement of beta power in the spontaneous EEG under the influence of benzodiazepine medication is a well known phenomenon under waking conditions as well as during sleep. On the other hand, in certain frequency bands EEG activity following external stimulation is also enhanced. Therefore, the question arises what relationship exists between pre- and poststimulus EEG under the influence of benzodiazepines. Is an augmentation of beta activity during benzodiazepine medication further enhanced when external stimulation is applied? In order to address this question we compared the spectral power of pre- and poststimulus EEG under 2.5 mg lorazepam during sleep with placebo conditions. The hypothesis tested was that of Basar (1980): if the beta power is high prior to the stimulation, no further enhancement following stimulation is observed. Our results confirm the hypothesis during sleep stages II and III. At the present time it is unclear whether this effect might be dose-dependent. In any case, the investigation presented here has furnished additional information on the mechanisms by which benzodiazepines alter the brain's electrical activity.

Acoustic Stimulation↗

Measuring nursing home resident satisfaction with food and food service: initial testing of the FoodEx-LTC.

BACKGROUND: Malnutrition impacts the quality of life and general health of many older persons living in our nation's 20,000 nursing homes (1). Despite the urgency of this issue, no instrument that measures resident satisfaction with food and food service was found in an extensive literature search. The purpose of this article is to describe the development and initial testing of a resident satisfaction with food and food service questionnaire (FoodEx-LTC) in the context of the Quality Nutrition Outcomes-Long-Term Care Model. METHODS: This pilot study was conducted in two phases. During phase one the instrument was developed, peer-reviewed, and pretested. Phase two further tested the instrument using a correlational design, measuring both intermediate and long-term outcomes found on the Quality Nutrition Outcomes-Long-Term Care Model. RESULTS: Hypothesis testing was used to measure construct validity. 4 of 5 FoodEx-LTC domains were significantly correlated with depression, 2 of 5 with serum albumin. The FoodEx-LTC demonstrates acceptable reliability for a new instrument. The coefficient alpha scores ranged from.69-.87 and test-retest correlations ranged from.55-.89, dependent upon domain. CONCLUSIONS: FoodEx-LTC appears to be a valid and reliable measure of resident food and food service satisfaction in nursing homes. This line of inquiry is of great importance because perceived quality of food and food service are strongly related to quality of life for residents in nursing homes, and adequate food intake is integral to maintaining weight and preventing protein-calorie malnutrition among elderly residents.

Aged↗

Impact of attachment styles on dream recall and dream content: a test of the attachment hypothesis of REM sleep.

We tested the hypothesis (McNamara 1996; Zborowski and McNamara 1998) that dream recall and dream content would pattern with interpersonal attachment styles. In study I, college student volunteers were assessed on measures of attachment, dream recall, dream content and other psychologic measures. Results showed that participants who were classified as 'high' on an 'insecure attachment' scale were significantly more likely to (a) report a dream, (b) dream 'frequently', and (c) evidence more intense images that contextualize strong emotions in their dreams as compared with participants who scored low on the insecure attachment scale. In study II, 76 community dwelling elderly volunteers completed measures of attachment, and dream recall. Participants whose attachment style was classified as 'preoccupied' were significantly more likely to report a dream and to report dreams with higher mean number of words per dream as compared with participants classified as 'securely' attached or as 'avoidant' or as 'dismissing.' Dream recall was lowest for the avoidant subjects and highest for the preoccupied subjects. These data support the view that rapid eye movement (REM) sleep and/or dreaming function, in part, to promote attachment.

Adult↗

An alternative to the use of two-sided tests in clinical trials.

There is a controversy in the literature concerning the use of one- and two-sided tests in clinical trials. Some contend that, when the research question relates to improved efficacy or safety, that is, the expected change is in one direction only, the hypothesis test should reflect this by being one-sided. Others insist on the use of a two-sided test in case a treatment difference in the opposite direction to that expected might turn up. We propose an alternative procedure to the two-sided test which also provides protection against overlooking a negative effect. The proposed procedure tests simultaneously for a positive difference and for equivalence. We illustrate the procedure by applying it to the results of a recent clinical trial.

Clinical Trials as Topic↗

Increased cortisol and decreased right ear advantage (REA) in dichotic listening following a negative mood induction.

This study aimed to evaluate neuroendocrine responses and changes in perceptual asymmetry following an induced negative affect. Cortisol increasing in response to negative affect has been reported, while current brain models of emotion processing link negative affect to the right hemisphere. In this study, the Velten Mood Induction Procedure was used to generate neutral or negative affect in 44 healthy subjects. The PANAS scales were used to assess self-reported mood. A consonant-vowel dichotic listening (DL) test was applied after the neutral and negative affect inductions, and levels of salivary cortisol were determined by radioimmunoassay. For the negative affect condition, and congruent with the hypothesis tested, PANAS positive scores diminished (p<0.001) and PANAS negative scores increased (p<0.001), yielding an inverse correlation between them. A significant increase in cortisol levels was also seen (p<0.04). When taking cortisol reactivity into account, PANAS negative scores were higher for high-than for low-cortisol responders (p<0.02). Regarding DL, an increase in left ear items (p<0.04) and a decrease in right ear items (p<0.03) reported for those subjects who obtained a right ear advantage in the neutral condition. An explanation in terms of Kinsbourne's model for attentional-activation influences on DL is postulated and implications for the issue of affective illness are also discussed.

Adult↗

On testing equivalence of three populations.

We consider analysis of clinical trials in which the objective is to show that three populations are equivalent. Equivalence is defined in terms of delta, the maximum difference in population means; a one-sided hypothesis test of delta is considered. We provide the distribution of the maximum pairwise difference in sample means, and we use this distribution to find critical values for tests of size 0.100, 0.050, 0.025, and 0.010. When standard errors are not equal among the three treatments, a simple adjustment is proposed to control the type I error rate. These tests are applied to studying the equivalence of three binomial proportions. Test-based confidence intervals are discussed. Two examples illustrate the proposed methods.

Analysis of Variance↗

Prolonged minor allograft survival in intravenously primed mice--a test of the veto hypothesis.

Experiments were performed to test the hypothesis that veto cells are responsible for the prolonged survival of minor allografts of skin that is observed in recipients primed intravenously with spleen cells from mice syngeneic with the skin donors. This prolonged survival was observed for each of several minor histocompatibility (H) antigens and is antigen-specific. Gamma radiation (3300 rads) abolished the ability of male spleen cells infused i.v. to delay the rejection of male skin grafts (H-Y antigen) on female recipients. However, depletion of Thy-1+ cells from the i.v. infusion failed to abolish the ability to prolong male skin graft survival. Furthermore, the prolonged survival accorded to B6 (H-2b) male skin grafts on CB6F1 (H-2b/H-2d) female recipients given i.v. infusions of B6 male spleen cells extended to BALB/c (H-2d) male skin grafts as well, indicating a lack of MHC restriction. Thus, prolongation of minor allograft survival by i.v. infusion of minor H antigen-bearing spleen cells appears not to depend on veto T cells that others have found to be responsible for the suppression of CTL generation (2, 3, 5).

Animals↗