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At least 1,189 records · Page 66Linked to original sources
PubMed2001

Pooling analysis of genetic data: the association of leptin receptor (LEPR) polymorphisms with variables related to human adiposity.

Analysis of raw pooled data from distinct studies of a single question generates a single statistical conclusion with greater power and precision than conventional metaanalysis based on within-study estimates. However, conducting analyses with pooled genetic data, in particular, is a daunting task that raises important statistical issues. In the process of analyzing data pooled from nine studies on the human leptin receptor (LEPR) gene for the association of three alleles (K109R, Q223R, and K656N) of LEPR with body mass index (BMI; kilograms divided by the square of the height in meters) and waist circumference (WC), we encountered the following methodological challenges: data on relatives, missing data, multivariate analysis, multiallele analysis at multiple loci, heterogeneity, and epistasis. We propose herein statistical methods and procedures to deal with such issues. With a total of 3263 related and unrelated subjects from diverse ethnic backgrounds such as African-American, Caucasian, Danish, Finnish, French-Canadian, and Nigerian, we tested effects of individual alleles; joint effects of alleles at multiple loci; epistatic effects among alleles at different loci; effect modification by age, sex, diabetes, and ethnicity; and pleiotropic genotype effects on BMI and WC. The statistical methodologies were applied, before and after multiple imputation of missing observations, to pooled data as well as to individual data sets for estimates from each study, the latter leading to a metaanalysis. The results from the metaanalysis and the pooling analysis showed that none of the effects were significant at the 0.05 level of significance. Heterogeneity tests showed that the variations of the nonsignificant effects are within the range of sampling variation. Although certain genotypic effects could be population specific, there was no statistically compelling evidence that any of the three LEPR alleles is associated with BMI or waist circumference in the general population.

Adipose Tissue↗
PubMed2002

Statistical analysis of timing errors.

Human rhythmic activities are variable. Cycle-to-cycle fluctuations form the behavioral observable. Traditional analysis focuses on statistical measures such as mean and variance. In this article we show that, by treating the fluctuations as a time series, one can apply techniques such as power spectra and rescaled range analysis to gain insight into the mechanisms underlying the remarkable abilities of humans to perform a variety of rhythmic movements, from maintaining memorized temporal patterns to anticipating and timing their movements to predictable sensory stimuli.

Humans↗
PubMedDate not supplied

Fractal character of the electrocardiogram: distinguishing heart-failure and normal patients.

Statistical analysis of the sequence of heartbeats can provide information about the state of health of the heart. We used a variety of statistical measures to identify the form of the point process that describes the human heartbeat. These measures are based on both interevent intervals and counts, and include the interevent-interval histogram, interval-based periodogram, rescaled range analysis, the event-number histogram, Fano-factor, Allan Factor, and generalized-rate-based periodogram. All of these measures have been applied to data from both normal and heart-failure patients, and various surrogate versions thereof. The results show that almost all of the interevent-interval and the long-term counting statistics differ in statistically significant ways for the two classes of data. Several measures reveal 1/f-type fluctuations (long-duration power-law correlation). The analysis that we have conducted suggests the use of a conveniently calculated, quantitative index, based on the Allan factor, that indicates whether a particular patient does or does not suffer from heart failure. The Allan factor turns out to be particularly useful because it is easily calculated and is jointly responsive to both short-term and long-term characteristics of the heartbeat time series. A phase-space reconstruction based on the generalized heart rate is used to obtain a putative attractor's capacity dimension. Though the dependence of this dimension on the embedding dimension is consistent with that of a low-dimensional dynamical system (with a larger apparent dimension for normal subjects), surrogate-data analysis shows that identical behavior emerges from temporal correlation in a stochastic process. We present simulated results for a purely stochastic integrate-and-fire model, comprising a fractal-Gaussian-noise kernel, in which the sequence of heartbeats is determined by level crossings of fractional Brownian motion. This model characterizes the statistical behavior of the human electrocardiogram remarkably well, properly accounting for the behavior of all of the measures studied, over all time scales.

Electrocardiography↗
PubMed2002

Analysis of comparative data using generalized estimating equations.

It is widely acknowledged that the analysis of comparative data from related species should be performed taking into account their phylogenetic relationships. We introduce a new method, based on the use of generalized estimating equations (GEE), for the analysis of comparative data. The principle is to incorporate, in the modelling process, a correlation matrix that specifies the dependence among observations. This matrix is obtained from the phylogenetic tree of the studied species. Using this approach, a variety of distributions (discrete or continuous) can be analysed using a generalized linear modelling framework, phylogenies with multichotomies can be analysed, and there is no need to estimate ancestral character state. A simulation study showed that the proposed approach has good statistical properties with a type-I error rate close to the nominal 5%, and statistical power to detect correlated evolution between two characters which increases with the strength of the correlation. The proposed approach performs well for the analysis of discrete characters. We illustrate our approach with some data on macro-ecological correlates in birds. Some extensions of the use of GEE are discussed.

Animals↗
PubMed2004

Application of a new statistical method to derive dietary patterns in nutritional epidemiology.

Because foods are consumed in combination, it is difficult in observational studies to separate the effects of single foods on the development of diseases. A possible way to examine the combined effect of food intakes is to derive dietary patterns by using appropriate statistical methods. The objective of this study was to apply a new statistical method, reduced rank regression (RRR), that is more flexible and powerful than the classic principal component analysis. RRR can be used efficiently in nutritional epidemiology by choosing disease-specific response variables and determining combinations of food intake that explain as much response variation as possible. The authors applied RRR to extract dietary patterns from 49 food groups, specifying four diabetes-related nutrients and nutrient ratios as responses. Data were derived from a nested German case-control study within the European Prospective Investigation into Cancer and Nutrition-Potsdam study consisting of 193 cases with incident type 2 diabetes identified until 2001 and 385 controls. The four factors extracted by RRR explained 93.1% of response variation, whereas the first four factors obtained by principal component analysis accounted for only 41.9%. In contrast to principal component analysis and other methods, the new RRR method extracted a significant risk factor for diabetes.

Alcohol Drinking↗
PubMedDate not supplied

Bioequivalence testing of a new tablet formulation of generic fluoxetine.

The pharmacokinetics and relative bioavailability of fluoxetine capsules (reference) and tablets (test) were compared in 24 healthy subjects of both sexes after a single 20 mg oral dose of fluoxetine (as a hydrochloride salt). A randomized, crossover design with a 2-week wash-out period between each dose was applied. Serum samples, obtained before dosing and at various appropriate time points up to 192 hours, were analyzed for fluoxetine and norfluoxetine content by a simple, accurate and precise HPLC method. ANOVA, power analysis, 90% confidence intervals (CI), and two one-sided tests were used for the statistical analysis of pharmacokinetic parameters. The tolerability of the preparations was good. The respective point estimates of the ratios of the geometric means of log-Cmax and log-AUC(0-infinity) of fluoxetine were 0.912 and 0.935 with 90% of 0.838-0.992 and 0.857-1.020. The corresponding point estimates of norfluoxetine were 0.952 (90% CI = 0.843-1.075) and 0.904 (90% CI = 0.807-1.013), respectively. Since both 90% CI for the AUC(0-infinity). and Cmax geometric mean ratios of fluoxetine and norfluoxetine were included in the 80% to 125% interval proposed by the FDA the test drug (fluoxetine tablets) was considered bioequivalent to the reference one (Prozac capsules) according both to the rate and extent of absorption.

Adult↗
PubMed2003

Increased fibroblast proliferation induced by light emitting diode and low power laser irradiation.

BACKGROUND AND OBJECTIVE: As Light Emitting Diode (LED) devices are commercially introduced as an alternative for Low Level Laser (LLL) Therapy, the ability of LED in influencing wound healing processes at cellular level was examined. STUDY DESIGN/MATERIALS AND METHODS: Cultured fibroblasts were treated in a controlled, randomized manner, during three consecutive days, either with an infrared LLL or with a LED light source emitting several wavelengths (950 nm, 660 nm and 570 nm) and respective power outputs. Treatment duration varied in relation to varying surface energy densities (radiant exposures). RESULTS: Statistical analysis revealed a higher rate of proliferation (p < 0.001) in all irradiated cultures in comparison with the controls. Green light yielded a significantly higher number of cells, than red (p < 0.001) and infrared LED light (p < 0.001) and than the cultures irradiated with the LLL (p < 0.001); the red probe provided a higher increase (p < 0.001) than the infrared LED probe and than the LLL source. CONCLUSION: LED and LLL irradiation resulted in an increased fibroblast proliferation in vitro. This study therefore postulates possible stimulatory effects on wound healing in vivo at the applied dosimetric parameters.

Animals↗
PubMed1996

Prognostic significance of quantitative electroencephalography in Alzheimer patients: preliminary observations.

In 31 Alzheimer outpatients followed up for a mean time of 26.4 months the hypothesis that quantitative electroencephalography (qEEG) could predict the loss of activities of daily living (ADL), the onset of incontinence, and death was tested by the Weibull proportional hazard model of 'lifereg' procedure of the Statistical Analysis System package. A central-posterior temporal region was considered in either side (power-weighted, log transformed relative values). Right delta predicted both the loss of ADL and death, whereas right theta predicted the onset of incontinence. Left values gave borderline significant results toward all end-points, whereas power-weighted mean frequency always gave borderline results. The curves calculated for predicted times may be a valid support for the clinician in attempting prognostic judgments of disease evolution.

Aged↗
PubMedDate not supplied

The SERENDIP piggyback SETI project.

The SERENDIP project is an ongoing program of monitoring and processing broadband radio signals acquired by existing radio astronomy observatories. SERENDIP operates in a piggyback mode: it makes use of whatever observing plan (sequence of frequencies, sky coordinates, and polarizations) is under way at its host observatory. Moreover, the SERENDIP data acquisition system, once installed, operates autonomously. This approach makes it possible to obtain large amounts of high quality observing time in a manner that is economical and that does not adversely affect ongoing radio astronomy survey work. The SERENDIP II system has been installed at the NRAO 300-foot telescope at Green Bank, West Virginia, and has operated there for several thousand hours. In this report, we summarize our findings from these observations and describe the present status of the project. Two key elements of SERENDIP are the automated data acquisition system that uses adaptive thresholds and logs only statistically significant peaks in the real-time power spectra, and the subsequent off-line analysis programs that identify and reject a variety of interference signals. Several specific correlations have been identified that offer promise. At present, the development and testing of these interference rejection algorithms is the main thrust of our work.

Algorithms↗
PubMed2004

Molecular docking and 3D QSAR studies on 1-amino-2-phenyl-4-(piperidin-1-yl)-butanes based on the structural modeling of human CCR5 receptor.

In the present study, we have used an approach combining protein structure modeling, molecular dynamics (MD) simulation, automated docking, and 3D QSAR analyses to investigate the detailed interactions of CCR5 with their antagonists. Homology modeling and MD simulation were used to build the 3D model of CCR5 receptor based on the high-resolution X-ray structure of bovine rhodopsin. A series of 64 CCR5 antagonists, 1-amino-2-phenyl-4-(piperidin-1-yl)-butanes, were docked into the putative binding site of the 3D model of CCR5 using the docking method, and the probable interaction model between CCR5 and the antagonists were obtained. The predicted binding affinities of the antagonists to CCR5 correlate well with the antagonist activities, and the interaction model could be used to explain many mutagenesis results. All these indicate that the 3D model of antagonist-CCR5 interaction is reliable. Based on the binding conformations and their alignment inside the binding pocket of CCR5, three-dimensional structure-activity relationship (3D QSAR) analyses were performed on these antagonists using comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) methods. Both CoMFA and CoMSIA provide statistically valid models with good correlation and predictive power. The q(2)(r(cross)(2)) values are 0.568 and 0.587 for CoMFA and CoMSIA, respectively. The predictive ability of these models was validated by six compounds that were not included in the training set. Mapping these models back to the topology of the active site of CCR5 leads to a better understanding of antagonist-CCR5 interaction. These results suggest that the 3D model of CCR5 can be used in structure-based drug design and the 3D QSAR models provide clear guidelines and accurate activity predictions for novel antagonist design.

Binding Sites↗
PubMed2006

New developments in exposure assessment: the impact on the practice of health risk assessment and epidemiological studies.

The field of exposure assessment has matured significantly over the past 10-15 years. Dozens of studies have measured the concentrations of numerous chemicals in many media to which humans are exposed. Others have catalogued the various exposure pathways and identified typical values which can be used in the exposure calculations for the general population such as amount of water or soil ingested per day or the percent of a chemical than can pass through the skin. In addition, studies of the duration of exposure for many tasks (e.g. showering, jogging, working in the office) have been conducted which allow for more general descriptions of the likely range of exposures. All of this information, as well as the development of new and better models (e.g. air dispersion or groundwater models), allow for better estimates of exposure. In addition to identifying better exposure factors, and better mathematical models for predicting the aerial distribution of chemicals, the conduct of simulation studies and dose-reconstruction studies can offer extraordinary opportunities for filling in data gaps regarding historical exposures which are critical to improving the power of epidemiology studies. The use of probabilistic techniques such as Monte Carlo analysis and Bayesian statistics have revolutionized the practice of exposure assessment and has greatly enhanced the quality of the risk characterization. Lastly, the field of epidemiology is about to undergo a sea change with respect to the exposure component because each year better environmental and exposure models, statistical techniques and new biological monitoring techniques are being introduced. This paper reviews these techniques and discusses where additional research is likely to pay a significant dividend. Exposure assessment techniques are now available which can significantly improve the quality of epidemiology and health risk assessment studies and vastly improve their usefulness. As more quantitative exposure components can now be incorporated into these studies, they can be better used to identify safe levels of exposure using customary risk assessment methodologies. Examples are drawn from both environmental and occupational studies illustrating how these techniques have been used to better understand exposure to specific chemicals. Some thoughts are also presented on what lessons have been learned about conducting exposure assessment for health risk assessments and epidemiological studies.

Bayes Theorem↗
PubMed2003

A combined neural network and decision trees model for prognosis of breast cancer relapse.

The prediction of clinical outcome of patients after breast cancer surgery plays an important role in medical tasks such as diagnosis and treatment planning. Different prognostic factors for breast cancer outcome appear to be significant predictors for overall survival, but probably form part of a bigger picture comprising many factors. Survival estimations are currently performed by clinicians using the statistical techniques of survival analysis. In this sense, artificial neural networks are shown to be a powerful tool for analysing datasets where there are complicated non-linear interactions between the input data and the information to be predicted. This paper presents a decision support tool for the prognosis of breast cancer relapse that combines a novel algorithm TDIDT (control of induction by sample division method, CIDIM), to select the most relevant prognostic factors for the accurate prognosis of breast cancer, with a system composed of different neural networks topologies that takes as input the selected variables in order for it to reach good correct classification probability. In addition, a new method for the estimate of Bayes' optimal error using the neural network paradigm is proposed. Clinical-pathological data were obtained from the Medical Oncology Service of the Hospital Clinico Universitario of Málaga, Spain. The results show that the proposed system is an useful tool to be used by clinicians to search through large datasets seeking subtle patterns in prognostic factors, and that may further assist the selection of appropriate adjuvant treatments for the individual patient.

Adult↗
PubMed1993

Continuous passive motion in the rehabilitation setting. A retrospective study.

Continuous passive motion (CPM) has been commonly used in the postoperative rehabilitation of patients after total knee arthroplasty. In the acute care hospital, most studies have found CPM to be useful in improving range of motion and reducing length of stay. The benefit of CPM in the rehabilitation hospital has not been studied. The charts of 61 patients who had undergone total knee arthroplasty and subsequently were admitted to the East facility of the Kessler Institute for Rehabilitation were reviewed. Patients were separated into two groups: Group 1 received CPM for 3 to 4 hours/day and physical therapy for 2 hours/day. Group 2 received only physical therapy. There was no significant difference in passive range of motion or length of stay between Group 1 and Group 2. An analysis of the 16 patients who underwent bilateral replacement was undertaken. Patients in Group 1 (n = 7) achieved an average increase in passive range of motion of 20.1 degrees, whereas those in Group 2 (n = 9) achieved an increase of 12.7 degrees (P = 0.18). Power analysis demonstrated the need for 50 patients per subgroup to achieve significance. The lack of statistical significance in this subgroup may be a reflection of the small study population (n = 16). The following conclusions can be drawn concerning the use of CPM in the rehabilitation setting: (1) CPM was of no added benefit to those patients admitted after single knee replacement, and (2) CPM may be beneficial to those patients admitted after bilateral knee replacement.

Aged↗
PubMedDate not supplied

A randomized trial to compare 7- and 21-day tetracycline regimens in the prevention of recurrence of infection with Chlamydia trachomatis.

Standard therapy for Chlamydia trachomatis in the United States consists of a 7-day course of tetracycline administration. Recurrent infections are frequent, however, in circumstances in which reinfection seems unlikely, suggesting that the standard regimen may be insufficient to cure the infection. It may reduce the number of organisms, however, below a detectable level at a test-of-cure visit. To evaluate recurrent infection, the authors studied patients with chlamydia who were treated with standard therapy, and they found a recurrence rate of 29% among 2,983 patients who returned to the clinic during a 2-year follow-up period. Recurrent infection was associated with younger age but was not related to either race or gender. To test the hypothesis that a longer treatment course might be more effective in preventing recurrent infection, the authors conducted a randomized trial that compared 7- and 21-day regimens of tetracycline administration. Of the 918 subjects enrolled in the trial, 220 were infected with C. trachomatis. The overall recurrence rate among patients who were infected and returned was 18.4% (9/49) in the 21-day group and 13.8% (8/58) in the 7-day group (P = .60). Similar results were obtained using survival analysis methods. Given the number of subjects who returned, this study had approximately a 65% statistical power to detect a reduction in recurrence rate, from 20% to 5%. Because of the similarity of the results in the two groups, it was concluded that 21 days of tetracycline administration is no more effective in preventing recurrence than 7 days of administration.

Adult↗
PubMed1999

Population pharmacokinetics of gentamicin in preterm neonates: evaluation of a once-daily dosage regimen.

Population pharmacokinetic parameters of gentamicin in preterm neonates on a once-daily dosage regimen of 3.0 mg/kg given intravenously every 24 hours were established prospectively. In 34 preterm neonates with a mean gestational age of 32 +/- 4 (SD), 182 serum gentamicin levels (91 peak/trough pairs) were determined. Individual adjustments of dose or dosage interval were calculated by computer-aided Bayesian forecasting. The parameters Vd, ke, and CL for each patient were obtained by the nonparametric estimation of maximization method. The predictive power of the model was calculated and the pharmacokinetic estimates were statistically analyzed with SPSS/PC. Cluster analysis showed a division into 2 subpopulations (designated 1 and 2) on the basis of postnatal age. The mean +/- SD postnatal age of subpopulation 1 (n = 29) was 6 +/- 2 days (range 1-7) and of subpopulation 2 (n = 5) 15 +/- 4 days (range 12-24). The mean +/- SD gentamicin relative clearances of subpopulation 1 and subpopulation 2 were 0.0515 +/- 0.0128 and 0.1026 +/- 0.0102 L kg(-1) hr(-1), respectively (p < 0.05). The mean +/- SD values for Vd (Lkg(-1)) in both populations 1 and 2 were 0.6916 +/- 0.1670 and 0.7509 +/- 0.1961, respectively (not significantly different). For ke these data were 0.0744 +/- 0.0200 and 0.1366 +/- 0.0522 (p < 0.05). Statistics showed that the data for Vd and ke of subpopulation 1 were normally distributed (Vd and ke skewness 1.61 and 1.46; kurtosis 3.09 and 3.10 respectively). The model yielded a bias of -0.11 mg/L and a precision of 0.36 mg/L. It is recommended that gentamicin be started in a dosage of 3.5 mg/kg intravenously once-daily under close monitoring.

Age Factors↗
PubMed1974

Concerning the statistical procedures enumerated by Gentile et al.: another perspective.

The thrust of this paper is to bring to the attention of operant researchers statistical procedures that are appropriate for correlated data. In addition to specifying these statistical procedures consideration is given to the question of using individual comparison statistics rather than omnibus F tests. Specifically, it is recommended that a more powerful test of the experimental hypotheses can be obtained by performing Bonferroni t statistics rather than analysis of variance F tests.

Journal Article↗
PubMed2003

Influence of 3 antivertiginous medications on the vigilance of healthy volunteers.

In the present randomized, comparative, double-blind, 3-way crossover study, possible effects of 3 antivertiginous medications on vigilance were investigated. 30 healthy volunteers received single doses of a fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg (Arlevert, ARL), dimenhydrinate 50 mg, or betahistine dimesylate 12 mg, in randomized order at 1-week intervals. Spontaneous brain electrical activity (EEG), acoustic late evoked potentials (ALEP) with P300, and reaction time were measured before and 90 (t90) and 180 minutes (t180) after drug intake. All 3 medications led to a delay of P300 (primary criterion) and a decrease of its amplitude. The maximum delay at t180 was found for dimenhydrinate (16.42 ms) and the lowest for betahistine (6.33 ms). Differences ARL vs dimenhydrinate and ARL vs betahistine were not statistically significant (p > 0.05). Spectral analysis of spontaneous EEG showed slight and similar decreases in the power in the a-band under dimenhydrinate and ARL (p = 0.07 and p = 0.03 with respect to baseline, respectively), but basically no change under betahistine. There was no effect on reaction time by either medication. None of the subjects reported drowsiness or any other adverse event. The findings confirm the reported suitability of P300 latency for measurement of drug effects on brain activity, but provide no indication of concomitant impairment of performance capacity by the tested drugs. Global assessment of the results suggests that the fixed combination cinnarizine 20 mg/dimenhydrinate 40 mg exerts only a minor effect on vigilance, not significantly different from betahistine, which is commonly regarded as a non-sedating antivertiginous drug

Adolescent↗
PubMed2000

CREST (Carotid Revascularization Endarterectomy versus Stent Trial): background, design, and current status.

The Carotid Revascularization Endarterectomy versus Stent Trial (CREST) contrasts the relative efficacy of carotid endarterectomy (CEA) and carotid angioplasty-stent (CAS) in preventing primary outcomes of stroke, myocardial infarction, or death during a 30-day periprocedural period, or ipsilateral stroke over the follow-up period extending up to 4 years. Stroke events will be verified by an Adjudication Committee masked to the assigned treatment. The primary eligibility criterion is a significant (> or =50%) stenosis of the carotid artery in patients with transient ischemic attack or ipsilateral nondisabling stroke within the prior 180 days. Men and women will be eligible for the trial, but patients with medical conditions likely to limit their participation during the follow-up or to interfere with outcome evaluation will be excluded. After a credentialing and training phase, 2,500 patients will be randomized to the treatments. Statistical analysis of the primary outcome will employ standard survival techniques and will result in 90% power to detect annual differences between groups of 1.2% or higher in event rates of the primary outcomes.

Carotid Stenosis↗