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PubMed1985

Control of children's observing responses by information feedback during visual discrimination learning.

Four experiments examined the control of observing responses by information feedback during visual discrimination learning. Second-grade children participated in Experiment 1; kindergarten, second-, and fifth-grade children were subjects in Experiments 2 and 3, and grade 5 and adult subjects were tested in Experiment 4. In order to view the stimuli, subjects in Experiments 1, 2, and 3 activated lights in viewing boxes; in Experiment 4, stimulus fixations were measured using a corneal reflection technique. Fifth graders and adults observed the discriminative stimuli for longer times on trials following negative feedback than on trials following positive feedback; in contrast, kindergartener's observing was not affected by type of feedback. Second graders showed smaller and less reliable reactions to type of feedback than did older subjects. These results support the view that visual observing is controlled by cognitive processes associated with hypothesis testing.

Child↗
PubMed2006

Reliability and validity testing of a short form of the Readiness Estimate and Deployability Index Revised for Air Force Nurses.

OBJECTIVE: The purpose of this study was to test the reliability and validity of the Readiness Estimate and Deployability Index Revised for Air Force Nurses Short Form, with a sample of 205 Air Force nurses. Participants were mostly female (70%), 36.31 +/- 9.3 years of age, with 11.52 +/- 7.17 years of nursing experience. METHODS: With structural equation modeling, the initial model did not fit the data (chi2/df = 5.45) and was revised. RESULTS: Revisions based on modification indices provided evidence of reliability (alpha coefficients of 0.70-0.94; the majority of R2 values were >0.50) and improved the fit of the model (chi2 difference, 35.54; df difference, 3.76; p < 0.05). Hypothesis testing provided evidence of construct validity. CONCLUSIONS: The 40-item Readiness Estimate and Deployability Index Revised for Air Force Nurses Short Form provides evidence of reliability and validity as a self-assessment measure of deployment preparedness.

Adaptation, Psychological↗
PubMed1989

Dysmorphogenesis of the mandible, zygoma, and middle ear ossicles in hemifacial microsomia and mandibulofacial dysostosis.

A review of the anatomical changes in patients with various "first arch" syndromes shows that some anomalies (e.g., micrognathia, ear defects) generally appear together. This study tested the hypothesis that the mandible, zygomatic arch, and middle ear ossicles are a developmental field (i.e., when any of these structures is anomalous, the other two will be also). The hypothesis was tested using data from 25 patients with mandibulofacial dysostosis (MFD) and 40 patients with hemifacial microsomia (HFM). Analysis of the pooled data showed that the hypothesis of character association was generally supported. However, the medians suggested that different factors probably played a role in determining how these three anatomical structures were associated in MFD and HFM. Errors in chondrogenesis may have been primarily responsible for the HFM phenotype. Alterations in Meckel and palatoquadrate cartilages would account for the size and shape changes observed in the ossicles and mandible, while changes in cranial base cartilages may explain the changes noted in the zygomatic arch. Since all three structures were equally affected in MFD, it is problematic to use an interference with chondrogenesis as an explanation for the phenotype. We conclude that although the mandible, zygomatic arch, and middle ear ossicles appear to form a "developmental field," the association between structures varies for HFM and MFD. The relatively lesser involvement of the zygomatic arch in HFM than in MFD suggests different pathogeneses for the two diagnostic groups and maybe a useful criterion for judging animal models of HFM.

Ear Ossicles↗
PubMed1994

The case for confidence intervals in controlled clinical trials.

A statistical wit once remarked that researchers often pose the wrong question and then proceed to answer that question incorrectly. The question that researchers intend to ask is whether or not a treatment effect is clinically significant. The question that is typically asked, however, is whether or not the treatment effect is statistically significant--a question that may be only marginally related to the issue of clinical impact. Similarly, the response, in the form of a p value, is typically assumed to reflect clinical significance but in fact reflects statistical significance. In an attempt to address this problem the medical literature over the past decade has been moving away from tests of significance and toward the use of confidence intervals. Concretely, study reports are moving away from "the difference was significant with a p value under 0.01" and toward "the one-year survival rate was increased by 20 percentage points with a 95% confidence interval of 15 to 24 percentage points." By focusing on what the effect is rather than on what the effect is not confidence intervals offer an appropriate framework for reporting the results of clinical trials. This paper offers a non-technical introduction to confidence intervals, shows how the confidence intervals framework offers advantages over hypothesis testing, and highlights some of the controversy that has developed around the application of this method. Additionally, we make the argument that studies which will be reported in terms of confidence intervals should similarly be planned with reference to confidence intervals. The sample size should be set to ensure that the estimates of effect size will be reported not only with adequate power but also with appropriate precision.

Confidence Intervals↗
PubMed2004

Prior convictions: Bayesian approaches to the analysis and interpretation of clinical megatrials.

Large, randomized clinical trials ("megatrials") are key drivers of modern cardiovascular practice, since they are cited frequently as the authoritative foundation for evidence-based management policies. Nevertheless, fundamental limitations in the conventional approach to statistical hypothesis testing undermine the scientific basis of the conclusions drawn from these trials. This review describes the conventional approach to statistical inference, highlights its limitations, and proposes an alternative approach based on Bayes' theorem. Despite its inherent subjectivity, the Bayesian approach possesses a number of practical advantages over the conventional approach: 1). it allows the explicit integration of previous knowledge with new empirical data; 2). it avoids the inevitable misinterpretations of p values derived from megatrial populations; and 3). it replaces the misleading p value with a summary statistic having a natural, clinically relevant interpretation-the probability that the study hypothesis is true given the observations. This posterior probability thereby quantifies the likelihood of various magnitudes of therapeutic benefit rather than the single null magnitude to which the p value refers, and it lends itself to graphical sensitivity analyses with respect to its underlying assumptions. Accordingly, the Bayesian approach should be employed more widely in the design, analysis, and interpretation of clinical megatrials.

Bayes Theorem↗
PubMed2003

Effect of test frequency on the in vitro fatigue life of acrylic bone cement.

The goal of the present work was to test the hypothesis that test frequency, f, does not have a statistically significant effect on the in vitro fatigue life of an acrylic bone cement. Uniaxial constant-amplitude tension-compression fatigue tests were conducted on 12 sets of cements, covering three formulations with three very different viscosities, two different methods of mixing the cement constituents, and two values of f (1 and 10 Hz). The test results (number of fatigue stress cycles, N(f)) were analyzed using the linearized form of the three-parameter Weibull equation, allowing the values of the Weibull mean (N(WM)) to be determined for each set. Statistical analysis of the lnN(f) data, together with an examination of the N(WM) estimates, showed support for the hypothesis over the range of f used. The principal use and explanation of the present finding are presented.

Acrylates↗
PubMed2005

Testing hypotheses regarding the genetics of adaptation.

Many of the hypotheses regarding the genetics of adaptation require that one know specific details about the genetic basis of complex traits, such as the number and effects of the loci involved. Developments in molecular biology have made it possible to create relatively dense maps of markers that can potentially be used to map genes underlying specific traits. However, there are a number of reasons to doubt that such mapping will provide the level of resolution necessary to specifically address many evolutionary questions. Moreover, evolutionary change is built upon the substitution of individual mutations, many of which may now be cosegregating in the same allele. In order for this developing area not to become a mirage that traps the efforts of an entire field, the genetic dissection of adaptive traits should be conducted within a strict hypothesis-testing framework and within systems that promise a reasonable chance of identifying the specific genetic changes of interest. Continuing advances in molecular technology may lead the way here, but some form of genetic testing is likely to be forever required.

Adaptation, Biological↗
PubMed2001

Distribution of the probability of survival is a strategic issue for randomized trials in critically ill patients.

BACKGROUND: Many randomized clinical trials in trauma have failed to demonstrate a significant improvement in survival rate. Using a trauma patient database, we simulated what could happen in a trial designed to improve survival rate in this setting. METHODS: The predicted probability of survival was assessed using the TRISS methodology in 350 severely injured trauma patients. Using this probability of survival, the authors simulated the effects of a drug that may increase the probability of survival by 10-50% and calculated the number of patients to be included in a triad, assuming alpha = 0.05 and beta = 0.10 by using the percentage of survivors or the individual probability of survival. Other distributions (Gaussian, J shape, uniform) of the probability of survival were also simulated and tested. RESULTS: The distribution of the probability of survival was bimodal with two peaks (< 0.10 and > 0.90). There were major discrepancies between the number of patients to be included when considering the percentage of survivors or the individual value of the probability of survival: 63,202 versus 2,848 if the drug increases the probability of survival by 20%. This discrepancy also occurred in other types of distribution (uniform, J shape) but to a lesser degree, whereas it was very limited in a Gaussian distribution. CONCLUSIONS: The bimodal distribution of the probability of survival in trauma patients has major consequences on hypothesis testing, leading to overestimation of the power. This statistical pitfall may also occur in other critically ill patients.

Adolescent↗
PubMed2003

Estimating times of surgeries with two component procedures: comparison of the lognormal and normal models.

BACKGROUND: Variability inherent in the duration of surgical procedures complicates surgical scheduling. Modeling the duration and variability of surgeries might improve time estimates. Accurate time estimates are important operationally to improve utilization, reduce costs, and identify surgeries that might be considered outliers. Surgeries with multiple procedures are difficult to model because they are difficult to segment into homogenous groups and because they are performed less frequently than single-procedure surgeries. METHODS: The authors studied, retrospectively, 10,740 surgeries each with exactly two CPTs and 46,322 surgical cases with only one CPT from a large teaching hospital to determine if the distribution of dual-procedure surgery times fit more closely a lognormal or a normal model. The authors tested model goodness of fit to their data using Shapiro-Wilk tests, studied factors affecting the variability of time estimates, and examined the impact of coding permutations (ordered combinations) on modeling. RESULTS: The Shapiro-Wilk tests indicated that the lognormal model is statistically superior to the normal model for modeling dual-procedure surgeries. Permutations of component codes did not appear to differ significantly with respect to total procedure time and surgical time. To improve individual models for infrequent dual-procedure surgeries, permutations may be reduced and estimates may be based on the longest component procedure and type of anesthesia. CONCLUSIONS: The authors recommend use of the lognormal model for estimating surgical times for surgeries with two component procedures. Their results help legitimize the use of log transforms to normalize surgical procedure times prior to hypothesis testing using linear statistical models. Multiple-procedure surgeries may be modeled using the longest (statistically most important) component procedure and type of anesthesia.

Algorithms↗
PubMed2006

Comparison between effectiveness of a low-viscosity glass ionomer and a resin-based glutaraldehyde containing primer in treating dentine hypersensitivity--a 25.2-month evaluation.

OBJECTIVES: The null-hypothesis tested was; there is no difference in effectiveness between a new low-viscosity glass ionomer and a resin-based glutaraldehyde containing primer in treating hypersensitive teeth after 2 years. METHODS: Using a split-mouth design, hypersensitive teeth in 14 adult patients were randomly assigned to 2 treatment groups. Hypersensitive tooth surfaces were covered with a low-viscosity glass ionomer (Fuji VII) and a resin-based glutaraldehyde containing primer (Gluma Desensitizer). The discomfort interval scale (DIS) ranging from 0 to 4 was used to test the level of hypersensitivity before and after treatment, and at 3 months using compressed air blown for 2 s, and at 1 and 25.2 months using a telephone interview. Differences between and within the treatment groups were tested using the sign rank test. RESULTS: Evaluations in the gluma group were discontinued after 3 months. The mean DIS score for hypersensitive teeth in the glass ionomer group was statistically significantly lower than that in the gluma group, immediately after application (p=0.0005), after 1 month (p=0.02) and after 3 months (p=0.003). After 3 months, 11/14 of the hypersensitive teeth in the glass ionomer group and 2/14 in the gluma group were free of sensitivity. The mean DIS score for hypersensitive teeth in the glass ionomer group remained low after 19.2 months (0.25: S.E.=0.13) and 25.2 months (0.22: S.E.=0.15). CONCLUSIONS: The null-hypothesis was rejected. The low-viscosity glass ionomer (Fuji VII) is more effective in treating hypersensitive teeth than Gluma Desensitizer after 3 months. The positive treatment effect of the glass ionomer continued until 25.2 months.

Adult↗
PubMed1979

Reflection-impulsivity and the evaluation process.

The relationship between reflection-impulsivity, hypothese generation and testing, and evaluation of the quality of one's own solutions was explored in the framework of Kagan's theory. The Matching Familiar Figures test (MFF) and a pattern-matching task were administered to 94 children from 8-0 to 11-11 years. Multiple regression analyses and analyses of variance showed that children who were inaccurate on the MFF were more likely to offer a solution on the pattern-matching task before they had sufficient information to guarantee a correct solution and to make errors despite sufficient information to have avoided those errors. Thus reflection-impulsivity as measured by the MFF were related to 2 other measures of the evaluation process on another visual match-to-sample task. Only 1 of 3 hypothesis-testing variables was significantly related to MFF performance, and that relationship was rather small.

Child↗
PubMed1999

A mixed effects model for the analysis of repeated measures cross-over studies.

A mixed effects model is developed for cross-over trials in which the response is measured repeatedly within each time period. Relative to previous work on repeated measures cross-overs, the methodology synthesizes two important features. First, our procedure eliminates preliminary testing for carry-over, defined loosely as the component of a response that is due to treatment in the preceding period. This is achieved by generalizing the methodology to cross-over designs in which preliminary testing for carry-over is unnecessary. We focus largely on 'simple' carry-over, that is, carry-over that lasts for exactly one period and is independent of the treatment administered in the period in which the carry-over occurs. However, we also illustrate a modification of the procedure for a repeated measures cross-over design which uses a more complicated model of carry-over. Second, the model allows both the between- and within-subject variance to differ among treatments. Conditions are described wherein closed-form (CF) solutions to the variance components as well as closed-form hypothesis tests of the treatment differences exist. Flexibility in the model is illustrated with an example in which inference based on the CF likelihood-based estimates of the variance, and estimates formed using an iterative routine (PROC MIXED) are compared.

Animals↗
PubMed2004

Cardiac output by Modelflow method from intra-arterial and fingertip pulse pressure profiles.

Modelflow, when applied to non-invasive fingertip pulse pressure recordings, is a poor predictor of cardiac output (Q, litre x min(-1)). The use of constants established from the aortic elastic characteristics, which differ from those of finger arteries, may introduce signal distortions, leading to errors in computing Q. We therefore hypothesized that peripheral recording of pulse pressure profiles undermines the measurement of Q with Modelflow, so we compared Modelflow beat-by-beat Q values obtained simultaneously non-invasively from the finger and invasively from the radial artery at rest and during exercise. Seven subjects (age, 24.0 +/- 2.9 years; weight, 81.2 +/- 12.6 kg) rested, then exercised at 50 and 100 W, carrying a catheter with a pressure head in the left radial artery and the photoplethysmographic cuff of a finger pressure device on the third and fourth fingers of the contralateral hand. Pulse pressure from both devices was recorded simultaneously and stored on a PC for subsequent Q computation. The mean values of systolic, diastolic and mean arterial pressure at rest and exercise steady state were significantly ( P < 0.05) lower from the finger than the intra-arterial catheter. The corresponding mean steady-state Q obtained from the finger (Qporta) was significantly ( P < 0.05) higher than that computed from the intra-arterial recordings (Qpia). The line relating beat-by-beat Qporta and Qpia was y =1.55 x -3.02 ( r2 = 0.640). The bias was 1.44 litre x min(-1) and the precision was 2.84 litre x min(-1). The slope of this line was significantly higher than 1, implying a systematic overestimate of Q by Qporta with respect to Qpia. Consistent with the tested hypothesis, these results demonstrate that pulse pressure profiles from the finger provide inaccurate absolute Q values with respect to the radial artery, and therefore cannot be used without correction with a calibration factor calculated previously by measuring Q with an independent method.

Adult↗
PubMed1998

Association study of asthma and atopy traits and chromosome 5q cytokine cluster markers.

BACKGROUND: Linkage studies have provided evidence for the presence of gene(s) in the 5q cytokine cluster region which control total serum immunoglobulin E (IgE) concentration, and bronchial hyperreactivity (BHR). However, the identification of the gene(s) involved has been confounded by the lack of power of the published linkage studies and the presence of multiple candidate genes mapped to the region. OBJECTIVE: To define the important loci on 5q31-33 which are implicated in the control of total serum IgE and BHR through a case/control study of association. METHODS: We performed an association study between 11 polymorphic markers (spanning the region 5q31.1-33.1) and total serum IgE and BHR traits. A case/control sample of 181 individuals was drawn from a larger set of 2415 adults, sampled at random from a district in Nottingham, UK. Half of the subjects in this case/control sample were hyperreactive to methacholine and asthmatic (cases), while the other half were non-reactive and non-asthmatic (controls). Association analysis was performed using the non-parametric chi-squared and Mann-Whitney U-tests. RESULTS: We observed no evidence of strong allelic association between any of the above markers and the studied traits. Markers D5S404, interferon regulatory factor 1 (IRF-1) and D5S210 showed evidence of borderline association with BHR (P = 0.04, 0.03 and 0.04 respectively), and D5S404 showed borderline significance with IgE levels (P = 0.029). CONCLUSIONS: This study presents evidence against the presence of a strong association between markers mapped to 5q31-33 and either BHR or total serum IgE. The significance of the weaker associations observed with markers D4S404, IRF-1 and D5S210 is not clear. Whether this represents a type I error secondary to multiple hypothesis testing or a true association is uncertain.

Adolescent↗
PubMed2004

Topical exposure to exogenous ultraviolet-irradiated urocanic acid enhances Mycobacterium ulcerans infection in a Crl:IAF(HA)-hrBR hairless guinea-pig model of Buruli ulcer disease.

BACKGROUND: Ultraviolet radiation (UVR) pre-exposure enhances Mycobacterium ulcerans infection in the Crl:IAF(HA)-hrBR hairless guinea-pig, possibly via a photoimmunosuppressive mechanism. The trans-cis photoisomerization of epidermal urocanic acid is an important initiator of the web of events leading to photoimmunosuppression. Thus, the hypothesis tested in this paper was that topical pre-exposure to UVR-irradiated urocanic acid mixture containing cis-urocanic acid (UVR-UCA) enhances the ulcerative form of M. ulcerans infection in the Crl:IAF(HA)-hrBR hairless guinea-pig model of human Buruli ulcer disease. METHODS: Groups of six animals were subjected to daily topical treatment with either 0 (vehicle only), 0.1, 0.5 or 1 mg of trans (tUCA) or UVR-UCA (contained a cis : trans urocanic acid isomer ratio of 1 : 9) for three consecutive days. A sham treatment group was also included in the experiment. Three days following their final treatment, the guinea-pigs were intradermally infected in the right dorsal flank with 1.5 x 107 CFU of M. ulcerans in 0.1 ml of phosphate-buffered saline (PBS) and sham infected with 0.1 ml of PBS in the left dorsal flank. The resultant skin lesions were then measured over the next 21 days. At day 21 postinfection, the animals were tested for delayed-type hypersensitivity (DTH) reactivity to M. ulcerans cell fragment antigens (MCF). RESULTS: Distinct, well-demarcated, dermally situated skin nodules were present at infected, but not sham-infected, skin sites by day 3 postinfection, and the lesions progressed to frank ulcers by day 5. Between days 5 and 21, the mean lesion diameters of the UVR-UCA-treated animals were significantly (P<0.001) greater than those of the sham, vehicle only or tUCA-treated groups. UVR-UCA-treated guinea-pigs also had significantly (P<0.001) suppressed DTH responses to MCF compared with the other treatment groups. There were no significant (P>0.4) differences between the lesion sizes and DTH responses of the tUCA, vehicle only or sham treatment groups. These results demonstrate that topical exposure to UVR-UCA promotes M. ulcerans infection and suppresses DTH responses to M. uclerans antigens in infected animals. These results lend credence to the hypothesis that UVR-mediated enhancement of Buruli ulcer disease in the Crl:IAF(HA)-hrBR hairless guinea-pig model occurs via modulation of cis-urocanic acid-susceptible immune pathways.

Animals↗
PubMed1998

A strong myelin thickness-axon size correlation emerges in developing nerves despite independent growth of both parameters.

The axon determines whether or not it is myelinated by the Schwann cell. At maturity there is a positive correlation between sheath thickness and axon calibre. This correlation is initially very low or absent, but gradually strengthens during development. This increase could come about because the axon continuously controls Schwann cell myelinating activity, so that a given axon calibre is associated with a particular myelin sheath thickness, an interaction which would entail the Schwann cell continuously monitoring and responding to axon size. This seems unnecessarily complex. This theoretical study shows that the strong correlation between the 2 parameters within a given myelinated fibre population may come about in a much simpler way than outlined above. This is demonstrated by modelling the growth and myelination of a hypothetical population, utilising data from earlier studies on cervical ventral motoneuron axon development. The hypothesis tested shows that the only instructive interactions by the axon on the Schwann cell necessary for the strong correlation between the 2 parameters to emerge are for the initiation of myelination, its continuation and its termination. These could result from a single stimulus being switched on, persisting for a time and being switched off. Under this influence, the Schwann cell is assumed to proceed to form the myelin sheath at a constant rate which it itself inherently determines, in the absence of any quantitative influence exerted by the axon. This continues until the stimulus for myelination ceases to emanate from the axon. The validity of the hypothesis is demonstrated, because the resulting myelin-axon relationships correspond closely to those observed during development.

Animals↗
PubMed2000

An exercise intervention for advanced cancer patients experiencing fatigue: a pilot study.

Fatigue is reported by advanced cancer patients to be their most prevalent and distressing symptom. Despite this, few interventions have been developed and tested to manage this debilitating symptom. This paper describes a pilot study undertaken to test the effects of a 28-day exercise intervention on levels of fatigue in advanced cancer patients. All participants were able to increase their activity levels with no increase in reported fatigue. Furthermore, a trend was noted in all patients toward increased quality of life scores and decreased anxiety scores. All participants described a sense of satisfaction in attaining increased activity levels. These preliminary pilot results suggest that patients who initially report the highest levels of fatigue may achieve the largest decrease in fatigue scores. These findings provide support for the suitability of this intervention for the palliative care population and justify the importance of further hypothesis testing.

Activities of Daily Living↗
PubMed2001

A test of the hypothesis that T3 is the "seasonality" thyroid hormone in American tree sparrows (Spizella arborea): intracerebroventricular infusion of iopanoic acid, an inhibitor of T3 synthesis and degradation.

This study tested the hypothesis that L-3,5,3'-triiodothyronine (T3) is the bioactive "seasonality" thyroid hormone in American tree sparrows (Spizella (arborea). The experimental approach coupled thyroid hormone replacement therapy after radiothyroidectomy with photostimulation and intracerebroventricular infusion of iopanoic acid, an inhibitor of L-3,5,3'-triiodothyronine synthesis and degradation. Endpoints were testis length, molt score, and hypothalamic content of chicken gonadotropin-releasing hormone 1. The hypothesis predicts that thyroidectomized male tree sparrows moved to long days and given thyroxine in combination with iopanoic acid will lack L-3,5,3'-triiodothyronine and so will not express thyroid hormone-dependent photoperiodic testicular growth (a vernal component of seasonality) and photorefractoriness or postnuptial molt (autumnal components of seasonality). It further predicts that iopanoic acid will enhance the efficacy of L-3,5,3'-triiodothyronine and so will facilitate the expression of seasonality in thyroidectomized males given L-3,5,3'-triiodothyronine replacement therapy. Iopanoic acid had no significant effect on any component of seasonality in thyroid-intact males given vehicle, or in thyroidectomized males given thyroxine or L-3,5,3'-triiodothyronine. Thyroid-intact males, as well as thyroidectomized males infused with thyroxine alone, commonly expressed all components of seasonality. Thyroidectomized males given L-3,5,3'-triiodothyronine alone exhibited photoperiodic testicular growth, but did not become photorefractory or initiate molt. While these results confirm that thyroid hormone acts centrally to program American tree sparrows for seasonality, they do not support the hypothesis that L-3,5,3'-triiodothyronine is the bioactive "seasonality" thyroid hormone, and they challenge the view that thyroxine is merely a prohormone.

Animals↗