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PubMed2004

Bootstrap white matter tractography (BOOT-TRAC).

White matter tractography is a noninvasive method for estimating and visualizing the white matter connectivity patterns in the human brain using diffusion tensor imaging (DTI) data. Sources of experimental noise may induce errors in the measured fiber directions, which will reduce the accuracy of the estimated white matter trajectories. In this study, a statistical nonparametric bootstrap method is described for estimating the dispersion and other errors in white matter tractography results. Prior studies have derived models of tractography error using the signal-to-noise ratio (SNR) and diffusion anisotropy of the DTI data. Tractography errors measured using bootstrap methods were generally consistent with an analytic model of tractography error except in areas where branching was evident. White matter tractography with bootstrap resampling is also applied to estimate the probabilities of connection between brain regions. The approach was used to generate probabilistic connectivity maps between the cerebral peduncles and specific cortical regions.

Brain↗

PubMed2005

The bootstrap: a technique for data-driven statistics. Using computer-intensive analyses to explore experimental data.

BACKGROUND: The concept of resampling data--more commonly referred to as bootstrapping--has been in use for more than three decades. Bootstrapping has considerable theoretical advantages when it is applied to non-Gaussian data. Most of the published literature is concerned with the mathematical aspects of the bootstrap but increasingly this technique is being utilized in medical and other fields. METHODS: I reviewed the published literature following a 1994 publication assessing the transfer of technology, including the bootstrap, to the biomedical literature. RESULTS: In the ten-year period following that 1994 paper there were 1679 published references to the technique in Medline. In that same time period the following citations were found in the four major medical journals-British Medical Journal (48), JAMA (51), Lancet (52) and the New England Journal of Medicine (45). CONTENT: I introduce the basic theory of the bootstrap, the jackknife, and permutation tests. The bootstrap is used to estimate the accuracy of an estimator such as the standard error, a confidence interval, or the bias of an estimator. The technique may be useful for analysing smallish expensive-to-collect data sets where prior information is sparse, distributional assumptions are unclear, and where further data may be difficult to acquire. Some of the elementary uses of bootstrapping are illustrated by considering the calculation of confidence intervals such as for reference ranges or for experimental data findings, hypothesis testing such as comparing experimental findings, linear regression, and correlation when studying association and prediction of variables, non-linear regression such as used in immunoassay techniques, and ROC curve processing. CONCLUSIONS: These techniques can supplement current nonparametric statistical methods and should be included, where appropriate, in the armamentarium of data processing methodologies.

Computers↗

PubMed2006

An fMRI task battery for assessing hemispheric language dominance in children.

Hemispheric dominance for language is an important issue in functional neuroimaging, particularly driven by efforts to overcome the need for the invasive Wada test, which is all the more pressing in children. Here, we aimed at developing new paradigms for functional magnetic resonance imaging (fMRI) for assessment of language dominance that can be used in younger children and allow for performance monitoring. Two new tasks (letter and animal task) were developed and compared to two reference tasks (synonyms and verb generation task) from the literature. Overall, 23 healthy children participated (13 boys, 10 girls, 10.2 +/- 2.5 years, range 6.1-15.3 years). Analysis was done using statistical nonparametrical mapping (SnPM2) on SPM2. Both reference tasks show activation in a number of left-frontal brain regions. The letter task induced a very localized activation in the left hemisphere's Broca's region, while not activating other frontal brain regions. Lateralization (as assessed in different anatomically and functionally defined regions) was consistent and strong. The animal task failed to activate frontal brain regions and was not suitable for assessing language dominance in children in this form. We conclude that while both reference tasks are useful for determining language dominance, they coactivate a number of task-related frontal areas not directly involved in language processing. Additionally, one task is not applicable in young children while the other does not allow performance monitoring. The letter task allows to selectively activate language areas in the dominant hemisphere and is applicable even in the very lowest age group amenable to fMRI investigations while still allowing performance monitoring. It may thus be a useful tool in assessing normal and pathological language organization.

Animals↗

PubMed1999

Outpatient exercise training in children with cystic fibrosis: physiological effects, perceived competence, and acceptability.

Exercise training is currently advocated as part of the treatment of patients with cystic fibrosis (CF). However, data are few that document physiologic benefits or changes in patients' perceptions of long-term training programs in children with CF. The aim of this study was to investigate the effects and acceptability of a home cycling program in children with CF. Fourteen patients (9 boys, 5 girls) with CF, mean (SD) age 14.1 (2.0) years, with mild to moderate impairment of lung function (forced expiratory volume in 1 s, mean (SD) 58.3 (16.3)% of predicted) were studied for 1 year. The first half of the study year was used to obtain baseline values at 0 and 6 months. During the second half of the year, a cycle program was carried out 5 times a week, for 20 min each day at a level of work that resulted in a heart rate of 140-160 beats/min. Once a week the cycle program was supervised by a physiotherapist. Measurements were repeated at 12 months. Effects of the exercise program were measured in terms of lung function, nutritional status, growth, muscle strength, exercise performance, perceived competence, and attitude towards the training program. Differences between the changes during the 6-month training period as compared to the 6-month control period were analyzed by multivariate statistics and nonparametric tests. Statistically significant differences (P < 0.05) between the two periods were found with respect to muscle strength of knee extensors and ankle dorsiflexors, and with respect to maximal oxygen consumption per kg body weight as well as per kg fat free mass. All changes were positive. No adverse effects were found. Perceived competence showed significant positive changes in feelings about physical appearance, general self-worth, and Total Perceived Competence Score. Scores concerning perceived acceptability of the program were significantly lower at the end of the training period; however, patients reported that they did want to continue with other sorts of training. We conclude that an exercise training program in the home can produce beneficial effects on oxygen consumption, muscle force, and perceived competence in children with CF. However, acceptability of the program was low, suggesting that long-term adherence would be poor, and hence, other sorts of training need to be identified.

Adolescent↗

PubMedDate not supplied

A nonparametric approach to the statistical analysis of mutagenicity data.

A nonparametric statistical method for analysing count data from mutagenicity tests is proposed. This method does not make any stringent assumptions on the variation of the data. It requires only one ranking of the observations and the calculation of a resulting test statistic. The significance of this statistic can be assessed by approximation to the standard normal distribution or tables of critical values calculated by the authors. The method also includes a descriptive component through a series of K-1 estimates of a trend in a K group experiment. Several examples are discussed to illustrate the proposed method.

Dose-Response Relationship, Drug↗

PubMed2003

On the use of permutation in and the performance of a class of nonparametric methods to detect differential gene expression.

MOTIVATION: Recently a class of nonparametric statistical methods, including the empirical Bayes (EB) method, the significance analysis of microarray (SAM) method and the mixture model method (MMM), have been proposed to detect differential gene expression for replicated microarray experiments conducted under two conditions. All the methods depend on constructing a test statistic Z and a so-called null statistic z. The null statistic z is used to provide some reference distribution for Z such that statistical inference can be accomplished. A common way of constructing z is to apply Z to randomly permuted data. Here we point our that the distribution of z may not approximate the null distribution of Z well, leading to possibly too conservative inference. This observation may apply to other permutation-based nonparametric methods. We propose a new method of constructing a null statistic that aims to estimate the null distribution of a test statistic directly. RESULTS: Using simulated data and real data, we assess and compare the performance of the existing method and our new method when applied in EB, SAM and MMM. Some interesting findings on operating characteristics of EB, SAM and MMM are also reported. Finally, by combining the idea of SAM and MMM, we outline a simple nonparametric method based on the direct use of a test statistic and a null statistic.

Algorithms↗

PubMedDate not supplied

Neurobehavioral evaluation in humans exposed to hydrocarbons: a new statistical approach.

BACKGROUND: Epidemiological researches showed a significant increase in the alterations of the cognitive and emotional sphere in subjects exposed to hydrocarbons. This paper deals with a study carried out on a group of male workers between the ages of 35 and 40, who had been working as external workers in a large refinery. METHODS: All the subjects worked in short shift rotation and were exposed to hydrocarbons during the loading of tank trucks. The response data reported by this investigation are compared to data of different male subjects who had also been working at the refinery for the same period of time, but as administrative day workers, and were certainly not exposed to the hydrocarbons. The nonparametric statistical analysis was carried out by a new nonparametric approach based on multivariate permutation tests. RESULTS: Results show a significant difference in the response to neurobehavioral tests. The exposed group showed behavioral tendencies towards anxiety and depression that the nonexposed group did not. CONCLUSIONS: The study shows that occupational exposure to hydrocarbons is associated with neurobehavioral modifications, and that the use of psychometric tests can be useful for monitoring the psychosomatic consequences by exposure to hydrocarbon microdoses.

Adult↗

PubMed2003

In vivo transgenic mutation assays.

Transgenic rodent gene-mutation models provide relatively quick and statistically reliable assays for gene mutations in the DNA from any tissue. This report summarizes those issues that have been agreed upon at a previous IWGT meeting [Environ. Mol. Mutagen. 35 (2000) 253], and discusses in depth those issues for which no consensus was reached before. It was previously agreed that for regulatory applications, assays should be based upon neutral genes, be generally available in several laboratories, and be readily transferable. For phage-based assays, five to ten animals per group should be analyzed, assuming a spontaneous mutant frequency (MF) of approximately 3x10(-5) mutants/locus and 125,000-300,000 plaque or colony forming units (pfu or cfu) per tissue per animal. A full set of data should be generated for a vehicle control and two dose groups. Concurrent positive control animals are only necessary during validation, but positive control DNA must be included in each plating. Tissues should be processed and analyzed in a blocked design, where samples from negative control, positive control and each treatment group are processed together. The total number of pfus or cfus and the MF for each tissue and animal are reported. Statistical tests should consider the animal as the experimental unit. Nonparametric statistical tests are recommended. A positive result is a statistically significant dose-response and/or statistically significant increase in any dose group compared to concurrent negative controls using an appropriate statistical model. A negative result is a statistically non-significant change, with all mean MFs within two standard deviations of the control. During the current workshop, a general protocol was agreed in which animals are treated daily for 28 consecutive days and tissues sampled 3 days after the final treatment. This recommendation could be modified by reducing or increasing the number of treatments or the length of the treatment period, when scientifically justified. Normally male animals alone are sufficient and normally at least one rapidly proliferating and one slowly proliferating tissue should be sampled. Although, as agreed previously, sequencing data are not normally required, they might provide useful additional information in specific circumstances, mainly to identify and correct for clonal expansion and in some cases to determine a mechanism associated with a positive response.

Animals↗

PubMedDate not supplied

Assessment of inter-rater agreement on the grading of intravascular bubble signals.

Transcutaneous Doppler ultrasonic bubble detectors are widely used in decompression research. However, interpretation of the complex acoustic signals from the bubble detectors involves a degree of subjectivity, and the comparability of grades assigned by different raters must be assessed. Hypothetical data were used to determine an appropriate method for evaluating the comparability of Doppler raters and to illustrate the limitations of many nonparametric statistics. Two sets of real data were then used to evaluate this procedure, the first from a training exercise carried out by Kisman and Masurel (1978, unpublished) and the second from a test tape that was independently scored by five Defence and Civil Institute of Environmental Medicine Doppler technicians. The results were analyzed by a two-stage approach. First, they were entered into contingency tables and checked for large disagreements, a tendency for one rater to grade higher than the other, and the degree of variability. Second, the results were analyzed with the nonparametric weighted kappa statistic. These studies have led to a practical, efficient method for the evaluation of Doppler raters.

Data Interpretation, Statistical↗

PubMed2000

In vivo transgenic mutation assays.

Transgenic rodent gene mutation models provide quick and statistically reliable assays for mutations in the DNA from any tissue. For regulatory applications, assays should be based on neutral genes, be generally available in several laboratories, and be readily transferable. Five or fewer repeated treatments are inadequate to conclude that a compound is negative but more than 90 daily treatments may risk complications. A sampling time of 35 days is suitable for most tissues and chemicals, while shorter sampling times might be appropriate for highly proliferative tissues. For phage-based assays, 5 to 10 animals per group should be analyzed, assuming a spontaneous mutant frequency (MF) of approximately 3 x 10(-5) mutants/locus and 125,000-300,000 plaque or colony forming units (PFU or CFU) per tissue. Data should be generated for two dose groups but three should be treated, at the maximum tolerated dose (MTD), two-thirds the MTD, and one-third the MTD. Concurrent positive control animals are only necessary during validation, but positive control DNA must be included in each plating. Tissues should be processed and analyzed in a block design and the total number of PFUs or CFUs and the MF for each tissue and animal reported. Sequencing data would not normally be required but might provide useful additional information in specific circumstances. Statistical tests used should consider the animal as the experimental unit. Nonparametric statistical tests are recommended. A positive result is a statistically significant dose-response and/or statistically significant increase in any dose group compared to concurrent negative controls using an appropriate statistical model. A negative result is statistically nonsignificant with all mean MF within two standard deviations of the control.

Animals↗

PubMed2001

Swedish nurses' attitudes towards research and development within nursing.

AIM OF THE STUDY: The aim was to develop and test an assessment instrument in order to study attitudes towards research and development within nursing among randomly selected professional nurses, registered nurses (RNs). BACKGROUND: The investigation was initiated because of the development within nursing and nursing education in Sweden towards better knowledge about research for the last four decades. METHODS: A questionnaire was designed, consisting of three parts: (1) demographic data, (2) attitude scale and (3) research awareness. Appropriate psychometric statistics were used such as factor analysis and parametric as well as nonparametric statistics to compare groups. The form was distributed to 407 randomly selected RNs. RESULTS: The response rate was 71% (n=289). The respondents were from four different examination years, representing four different nursing education systems in Sweden. Factor analysis (Maximum Likelihood and Oblimin rotation) gave seven factors with a total variance of 58% and Cronbach's alpha between 0.60 and 0.84. The factors were labelled 'Research language', 'Need of research knowledge', 'Participation', 'The Profession', 'Meaningfulness', 'Study literature' and 'Developing - Resources'. The results indicated that the respondents in general had positive attitudes towards nursing research. There were significant differences between the examined groups. The group examined in 1966 appeared as the least positive group. Forty-six per cent never or seldom utilized nursing research findings in their daily practice. About half of the respondents never read research reports. CONCLUSION: The results indicated that the new instrument is sensitive for measuring professional nurses' attitudes towards research and development in nursing. Even if the respondents had a positive attitude towards research and development, there was a poor application in their daily work. Further, the respondent's age, the year of RN examination and acquisition of research skills seemed to be of importance for the attitudes.

Adult↗

PubMed1992

Relationship between urinary cotinine level and diagnosis in children admitted to hospital.

The reported association between passive smoking and respiratory illness in children has been based on the parents' assessment of their own level of smoking. To more critically evaluate a causal relationship between passive smoking and childhood ill health, we used urinary cotinine, which is the major metabolite of nicotine and has a long half-life, to objectively quantitate the level of passive smoking in children. Urine was collected from 609 children (median age 3.8 yr, range 1 month to 17 yr) on admission to hospital; cotinine levels were obtained in 491 of these samples, and a comprehensive respiratory questionnaire was completed for 468 children. Statistical analysis was carried out on transformed data using both parametric and nonparametric statistics. Cotinine levels in the children correlated with the parents' current smoking (p less than 0.001). Elevated levels were found in the 41 children admitted with bronchiolitis compared with a group of a similarly aged children with nonrespiratory illnesses (p less than 0.02). Elevated levels were not found for any other diagnosis. We conclude that the urinary cotinine approach has provided objective evidence linking passive smoking to hospital admission for bronchiolitis in infants.

Adolescent↗

PubMed1998

Food interaction pharmacokinetic study of cordaflex 20 mg retard filmtablet in healthy volunteers.

The aim of the present study was to investigate the effect of food consumption on the pharmacokinetics of Cordaflex 20 mg retard filmtablet in healthy volunteers through measuring nifedipine plasma levels by an HPLC-ED method both after fasting and food ingestion. The food interaction pharmacokinetic study of Cordaflex 20 mg retard filmtablet was carried out in 12 healthy male volunteers treated with a single dose of the preparation both after fasting and after food ingestion, in a crossover design allowing 1 week of wash-out period between the 2 treatments. Nifedipine concentration of plasma samples were determined by an isocratic HPLC-ED method [Horvai et al. 1994] with robotic sample processing [Horváth et al. 1995, 1996]. The pharmacokinetic parameters (AUC0-infinity, AUC0-t, Cmax, MRT) were analyzed by calculating 90% confidence interval for logarithmic transformed test/reference ratio values, and Schuirmann's statistical tests, the tmax and HVD values were analyzed by Wilcoxon's nonparametric statistical test. The above statistical tests of the present food interaction study indicated significant differences for each one of the respective pharmacokinetic parameter pairs calculated for treatments after fasting and after food ingestion. On the basis of the above findings and also by comparing the mean pharmacokinetic curves, it was evident, that, in agreement with the data of literature [Kleinbloesem et al. 1993, Schall et al. 1994], food ingestion increased the relative bioavailability and maximum plasma concentration (Cmax). Considering the average of the parameter values and also the respective statistical tests, it was also apparent that the time to maximum plasma concentration (tmax), the mean residence time (MRT), and the half-value duration (HVD) all decreased significantly upon the effect of food ingestion.

Administration, Oral↗

PubMedDate not supplied

Evaluation of tracheal diameter after surgical tracheostomy.

PURPOSE: The aim of this study was to evaluate the narrowing of the trachea in head and neck surgical patients who had undergone elective tracheostomy. MATERIALS AND METHODS: This is a prospective study. Twenty-five patients were included in this study. All these patients had a preoperative elective tracheotomy, preceding major head and neck surgery for head and neck malignancies. An x-ray of the lateral soft tissue neck was taken after a minimum of 6 weeks after the dissimulation of tracheotomy tube. Diameter of the trachea above the stoma (around 2 cm below the cricoid ring that can be clearly seen in lateral x-ray corresponding to the second tracheal ring) was taken as controls. Data were entered into a computer database and statistically analyzed using SPSS for Windows (version 12.0; SPSS, Chicago, Ill). In addition to descriptive statistics for all patients, inferential statistics were used to compare the 2 tracheal diameters across all patients and within the subgroups of men and women. Associations between outcome and other variables were evaluated statistically using an chi 2 test for the categorical data. Other parametric and nonparametric statistical tests were used when appropriate. Criterion for statistical significance was set at P < .05 (Student t test and 2-tailed test). RESULTS: From this study, 92% (23/25) patients developed narrowing of trachea, all less than 50%. Very early decanulation of tracheotomy shows low or no narrowing at all. There is gradual narrowing in patients in whom dissimulations were performed after 14 days. Ethnicities of Indian decent (13/25) predominate in this study population. Male patients in this study have shorter decanulation period compared with female. CONCLUSIONS: Elective surgical tracheotomy is a relatively safe procedure resulting in minimum asymptomatic tracheal stenosis.

Adult↗

PubMed2004

Analysis of cerebral infarction pattern in computed tomography images of patients with internal carotid artery stenosis.

RATIONALE AND OBJECTIVES: An unbiased and quantitative analysis of lesion patterns in patient groups is described and applied to the analysis of infarction patterns. MATERIALS AND METHODS: One hundred forty-two computed tomographic images of patients with ischemic stroke were registered to an average computed tomographic brain image, which was used as template. Lesions were segmented manually and averaged per category of internal carotid artery (ICA) stenosis. Thus, patterns of lesion distribution were formed. Differences then were analyzed using nonparametric statistics. This analysis was compared with the traditional classification of lesions. RESULTS: The nonparametric analysis showed an increased involvement of the territory of the middle cerebral artery in infarctions in patients with ICA occlusion compared with patients with mild or severe ICA stenosis. These differences did not show when classification of infarctions was used. CONCLUSIONS: The presented method is more sensitive to differences in lesion patterns than traditional lesion classification and showed a different infarction pattern for ICA occlusion.

Aged↗

PubMed1994

Use of statistical analysis in the AJR and Radiology: frequency, methods, and subspecialty differences.

OBJECTIVE: The statistical procedures appearing in Radiology and the AJR were analyzed to determine the types of statistical tests used in major articles, their relative frequencies, and whether these methods differed according to radiologic subspecialty. MATERIALS AND METHODS: Six hundred sixty-nine major articles published in Radiology or the AJR during 1993 were reviewed for statistical content. These articles were first classified by radiologic subspecialty or principal focus according to the named journal section where each appeared (e.g., breast imaging, musculoskeletal radiology, neuroradiology). The statistical methods used in each article were then assigned to one of 18 categories (e.g., descriptive, basic t- and z-tests, correlation/regression techniques, and nonparametric statistics). RESULTS: Of the 669 major articles analyzed, 294 (44%) used no statistical methods or descriptive statistics only, 179 (27%) used only one type of statistical method, 102 (15%) used two methods, and 94 (14%) used three or more methods. Statistical techniques were most likely to be used in articles classified as cardiac (85% used statistical analysis) or contrast agents (79%), but least likely to be used in gastrointestinal/abdominal imaging (45%), radiotherapy (44%), or miscellaneous topics (29%). Five basic categories of statistical methods--basic z- and t-tests, basic decision statistics (sensitivity, specificity), basic contingency table analysis (chi 2, McNemar), correlation/regression techniques (linear regression, Pearson coefficients), and basic nonparametric tests (Wilcoxon, Mann-Whitney U)--account for the complete statistical analysis appearing in approximately 80% of the major articles. CONCLUSION: Approximately half the major articles appearing in Radiology or AJR used no statistics, descriptive analysis only, or a simple inferential test employing t-tests or confidence intervals; advanced statistical techniques were found in only 20% of articles. Statistical analysis was most likely to be used in articles dealing with cardiac radiology or contrast agents and least likely to be used in articles on abdominal/gastrointestinal radiology, radiotherapy, and miscellaneous radiologic topics.

Humans↗

PubMed1991

Surgical versus percutaneous drainage of intra-abdominal abscesses.

The records of 83 patients with intra-abdominal abscesses treated between 1986 and 1990 were reviewed to determine if there were significant differences in the outcome of patients treated by surgical drainage (n = 41) or percutaneous drainage (n = 42). The two groups were matched for age, abscess location, and etiology. Parametric statistical evaluations included the Student's t test as well as analysis of variance; nonparametric statistics used were chi-square and Wilcoxon rank sums. No significant difference was found in mortality (surgical 14% versus percutaneous 12%) or morbidity (surgical 26% versus percutaneous 29%). The duration of hospital stay was similar. Although there was no significant difference between the two groups in severity of illness as measured by APACHE II scores, these scores were significant in determining prognosis. APACHE II scores were significantly higher in non-survivors of both groups (23 versus 13) and also higher in those developing complications. A subgroup of patients with diverticular abscess was identified in whom percutaneous drainage enabled later resection with primary anastomosis without complication. This study indicates that percutaneous drainage of an intra-abdominal abscess is as efficacious as surgical drainage and that APACHE II scores are prognostic of both potential mortality and morbidity.

Abdomen↗

PubMed2001

Saturated fat intake is reduced in patients with ischemic heart disease 1 year after comprehensive counseling but not after brief counseling.

OBJECTIVE: To examine the dietary habits of patients with ischemic heart disease 1 year after they received either dietary advice on using the Plate Model and how to increase intakes of fruits and vegetables in a 10-minute session (brief counseling group, BCG) or dietary advice primarily based on the National Cholesterol Education Program Step I diet provided in 2 individually tailored 50-minute sessions held 3 months apart (comprehensive counseling group, CCG). DESIGN: A randomized study that included dietary intake evaluation on basis of 7-day weighed food records completed at 3 occasions: immediately before counseling (week zero), 12 weeks after counseling, and 52 weeks after counseling. SUBJECTS: BCG was composed of 15 men and 2 women and CCG was composed of 16 men and 3 women with ischemic heart disease age 70 years or younger recruited from the Department of Cardiology, Odense University Hospital, Odense, Denmark. STATISTICAL ANALYSES PERFORMED: ANOVA, unpaired t tests, and multiple regression analysis, as well as nonparametric statistical analyses were carried out. RESULTS: The comprehensive counseling resulted in significant improvements from week 0 to 52 in the percent of energy from fat (33% to 28%), saturated fat (12% to 9%) and carbohydrate (51% to 54%) consumed by the subjects. The corresponding values in BCG did not differ significantly (31% to 32%, 11% to 12%, 53% to 52% respectively). Differences from week 0 to 52 between groups were significant for fat, saturated fat, and carbohydrate intake. In CCG, median intakes of fish, fruits, and vegetables were 44 g/day, 172 g/day, and 315 g/day, respectively, at week 52. The corresponding values in BCG were 44 g/day, 129 g/day, and 224 g/day. There was no significant difference either within or between the groups. CONCLUSION: This study suggests that sustained improvements in dietary behavior require individualized and reinforced counseling in patients with ischemic heart disease. Changes in intakes of fish, fruits, and vegetables need to be specifically targeted.

Aged↗