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PubMed1998

Nonparametric estimation of covariance structure in longitudinal data.

In longitudinal studies, the effect of various treatments over time is usually of prime interest. However, observations on the same subject are usually correlated and any analysis should account for the underlying covariance structure. A nonparametric estimate of the covariance structure is useful, either as a guide to the formulation of a parametric model or as the basis for formal inference without imposing parametric assumptions. The sample covariance matrix provides such an estimate when the data consist of a short sequence of measurements at a common set of time points on each of many subjects but is impractical when the data are severely unbalanced or when the sequences of measurements on individual subjects are long relative to the number of subjects. The variogram of residuals from a saturated model for the mean response has previously been suggested as a nonparametric estimator for covariance structure assuming stationarity. In this paper, we consider kernel weighted local linear regression smoothing of sample variogram ordinates and of squared residuals to provide a nonparametric estimator for the covariance structure without assuming stationarity. The value of the estimator as a diagnostic tool is demonstrated in two applications, one to a set of data concerning the blood pressure of newborn babies in an intensive care unit and the other to data on the time evolution of CD4 cell numbers in HIV seroconverters. The use of the estimator in more formal statistical inferences concerning the mean profiles requires further study.

Anti-HIV Agents↗

PubMed2006

Dynamic MR perfusion and proton MR spectroscopic imaging in Sturge-Weber syndrome: correlation with neurological symptoms.

PURPOSE: To investigate physiological alterations in Sturge-Weber syndrome (SWS) using MR perfusion imaging (PWI) and proton spectroscopic imaging (MRSI), and their association with neurological status. MATERIALS AND METHODS: Six consecutive patients with a clinically established diagnosis of SWS underwent MRI using a 1.5 Tesla scanner. The protocol consisted of conventional anatomic scans, dynamic PWI, and multislice MRSI. A pediatric neurologist evaluated the neurological scores, and the imaging results were correlated with neurological scores using nonparametric correlation analysis. RESULTS: Two patients had classic neuroimaging findings of unilateral cerebral atrophy with corresponding leptomeningeal enhancement and hypoperfusion (prolonged mean transit time). Two patients had bilateral disease, and two had normal symmetric perfusion. Among clinical measures, the highest correlation was between hemiparesis index and hypoperfused tissue volume (Spearman's correlation coefficient, rho = 0.943, P < 0.05). There was also a trend of correlation, although not statistically significant (P = 0.06), between the hemiparesis score and the NAA/Cr ratio in the mid to posterior centrum semiovale, lateral gray matter (GM), and splenium. CONCLUSION: In SWS, PWI indicates cerebral hypoperfusion predominantly due to impaired venous drainage, with only the most severely affected regions in some patients also showing arterial perfusion deficiency. The extent and severity of the perfusion abnormality and neuronal loss/dysfunction reflect the severity of neurological symptoms and disability, and the highest correlation is found with the degree of hemiparesis. These parameters may be useful as quantitative measures of disease burden; however, further studies in larger number of patients (and with a more homogeneous age range) are required to confirm the preliminary findings reported here.

Adolescent↗

PubMed2002

The influence of dental operating microscope in locating the mesiolingual canal orifice.

OBJECTIVE: The purpose of this study was to evaluate the influence of using the dental operating microscope (DOM) for detection of the mesiolingual (ML) canal orifice in extracted maxillary molars compared with unaided vision (no loupes or headlamps). STUDY DESIGN: Using a clinical simulation model system, we mounted 39 maxillary molars in a dentoform and placed them into a mannequin. After rubber dam placement and preparation of standard access, 2 attempts were made to locate the ML canal with unaided vision. Then the teeth were examined by using a DOM. Finally, all teeth were sectioned, stained, and evaluated with the DOM for actual presence of an ML canal. RESULTS: ML canal orifices were detected in 20 of the teeth with a sharp explorer and mirror. In the remaining teeth, 12 ML canal orifice were located by using the DOM. Qualitative nonparametric comparisons were used. CONCLUSIONS: The results of this study indicate that the DOM provides increased opportunity for the dentist to detect canal orifices.

Dental Equipment↗

PubMed2006

Nonparametric estimation of transition probabilities in a non-Markov illness-death model.

In this paper we consider nonparametric estimation of transition probabilities for multi-state models. Specifically, we focus on the illness-death or disability model. The main novelty of the proposed estimators is that they do not rely on the Markov assumption, typically assumed to hold in a multi-state model. We investigate the asymptotic properties of the introduced estimators, such as their consistency and their convergence to a normal law. Simulations demonstrate that the new estimators may outperform Aalen-Johansen estimators (the classical nonparametric tool for estimating the transition probabilities) in non-Markov situation. An illustration through real data analysis is included.

Adrenergic beta-Antagonists↗

PubMed2003

Hypothesis testing in semiparametric additive mixed models.

We consider testing whether the nonparametric function in a semiparametric additive mixed model is a simple fixed degree polynomial, for example, a simple linear function. This test provides a goodness-of-fit test for checking parametric models against nonparametric models. It is based on the mixed-model representation of the smoothing spline estimator of the nonparametric function and the variance component score test by treating the inverse of the smoothing parameter as an extra variance component. We also consider testing the equivalence of two nonparametric functions in semiparametric additive mixed models for two groups, such as treatment and placebo groups. The proposed tests are applied to data from an epidemiological study and a clinical trial and their performance is evaluated through simulations.

Anticonvulsants↗

PubMed2001

Nonparametric frontier model as a tool for exploratory analysis of hospital stays.

Diagnosis-related groups (DRG) were introduced in 1995 to the Belgian hospital financing system. Trimming rules are generally used when mean length of stay (LOS) is estimated by DRG. This paper proposes the use of frontier models instead of trimming rules. These models allow to take into account the characteristics of the patients, to rank hospital stays, and to indicate stays presenting discrepancy between the patient's characteristics and the resources consumed. The analysis is done with the nonparametric Free Disposal Hull (FDH) model and the method developed by Wilson to detect extreme observations, when defining the frontier is adapted to analyze large databases.

Belgium↗

PubMed2001

Association of ABO-mismatched platelet transfusions with morbidity and mortality in cardiac surgery.

BACKGROUND: The transfusion of ABO-mismatched platelets has been associated with increased morbidity and mortality during induction therapy for acute leukemia and allogeneic progenitor cell transplantation. STUDY DESIGN AND METHODS: Reported here is a cohort study of 153 patients undergoing primary coronary artery bypass graft or coronary valve replacement surgery by two surgeons in one institution during 1997 and 1998. All statistics employed nonparametric two-sided tests (Mann-Whitney; Fisher's exact test). RESULTS: Patients receiving at least one ABO-mismatched pool of platelets had a significantly longer hospital stay, more days of fever, greater total hospital charges, and more RBC transfusions. Mortality, hours in the intensive care unit, days on antibiotics, and numbers of platelet transfusions were also greater in recipients of ABO-mismatched platelets, but these differences were of less statistical significance. When the analysis was restricted to the 139 patients who received no more than two pools of platelets, the trends for increased morbidity and mortality (8.6% vs. 1.9%; p = 0.10) in recipients of ABO-mismatched platelets persisted. The number of RBC transfusions required in this latter cohort was 50 percent greater (mean, 6.1 vs. 9.2; p = 0.02), despite the fact that the number of platelet transfusions given was similar (mean, 1.2 vs. 1.3 pools; p = 0.22). CONCLUSIONS: ABO-mismatched platelet transfusions are associated with unfavorable outcomes in cardiac surgery, a relationship that remains unexplained. As this association has been found in three cohort studies in various clinical settings, further investigation of this association is warranted.

ABO Blood-Group System↗

PubMed2003

Accuracy of open tray implant impressions: an in vitro comparison of stock versus custom trays.

STATEMENT OF PROBLEM: The accuracy of an implant fixture-level impression is affected by the type of impression tray used. PURPOSE: The purpose of this in vitro study was to investigate the accuracy of open tray implant impressions comparing polycarbonate stock impression trays and rigid custom-made impression trays to make implant fixture-level impressions. MATERIAL AND METHODS: Gold cylinder pairs, splinted by gold bars (reference frameworks) were constructed on an aluminum typodont. Polyether impressions were made of 2 pairs of Brånemark 3.75-mm diameter fixtures mounted in an aluminium typodont, with 3 stock impression trays, 3 close-fit custom trays, and 3 spaced custom impression trays, by use of an open tray technique. The casts produced were assessed for accuracy by attaching the reference frameworks with alternate single screws and measuring the vertical fit discrepancy of these reference frameworks to the analogs within the working cast using a traveling microscope. Comparison of gap dimensions by tray type was performed with a nonparametric Kruskal-Wallis analysis of variance (ANOVA) followed by pair-wise Mann-Whitney U tests. To adjust for multiple comparisons in the post-ANOVA contrasts (P<.02). Comparison of gap dimensions between anterior and posterior regions were performed with Mann-Whitney U tests (P <.05). RESULTS: The results showed that the mean fit accuracy, as measured by vertical fit discrepancy, of casts from the stock trays (23 +/- 20 microm) were statistically significantly less (P<.001) than the spaced custom trays (12 +/- 10 microm) or close fit custom trays (11 +/- 10 microm). The difference in median gap size for analogs with a 20-mm separation was 10 microm. CONCLUSION: Within the limits of this in vitro study, rigid custom trays produced significantly more accurate impressions than the polycarbonate stock trays. The stock trays used in this study could not produce accurate impressions consistently. For analogs with a 20-mm separation, there was a difference in medians of 10 microm in accuracy between the stock and custom trays.

Analysis of Variance↗

PubMed2005

Identifying genomic regions for fine-mapping using genome scan meta-analysis (GSMA) to identify the minimum regions of maximum significance (MRMS) across populations.

In order to detect linkage of the simulated complex disease Kofendrerd Personality Disorder across studies from multiple populations, we performed a genome scan meta-analysis (GSMA). Using the 7-cM microsatellite map, nonparametric multipoint linkage analyses were performed separately on each of the four simulated populations independently to determine p-values. The genome of each population was divided into 20-cM bin regions, and each bin was rank-ordered based on the most significant linkage p-value for that population in that region. The bin ranks were then averaged across all four studies to determine the most significant 20-cM regions over all studies. Statistical significance of the averaged bin ranks was determined from a normal distribution of randomly assigned rank averages. To narrow the region of interest for fine-mapping, the meta-analysis was repeated two additional times, with each of the 20-cM bins offset by 7 cM and 13 cM, respectively, creating regions of overlap with the original method. The 6-7 cM shared regions, where the highest averaged 20-cM bins from each of the three offsets overlap, designated the minimum region of maximum significance (MRMS). Application of the GSMA-MRMS method revealed genome wide significance (p-values refer to the average rank assigned to the bin) at regions including or adjacent to all of the simulated disease loci: chromosome 1 (p < 0.0001 for 160-167 cM, including D1), chromosome 3 (p-value < 0.0000001 for 287-294 cM, including D2), chromosome 5 (p-value < 0.001 for 0-7 cM, including D3), and chromosome 9 (p-value < 0.05 for 7-14 cM, the region adjacent to D4). This GSMA analysis approach demonstrates the power of linkage meta-analysis to detect multiple genes simultaneously for a complex disorder. The MRMS method enhances this powerful tool to focus on more localized regions of linkage.

Chromosomes, Human↗

PubMed2004

Nonparametric prediction of event times in randomized clinical trials.

In clinical trials with planned interim analysis, it can be valuable for logistical reasons to predict the times of landmark events such as the 50th and 100th event. Bagiella and Heitjan (Stat Med 2001; 20: 2055-63) proposed a parametric prediction model for failure-time outcomes assuming exponential survival and Poisson enrollment. When little is known about the distributions of interest, there is concern that parametric prediction methods may be biased and inefficient if their underlying distributional assumptions are invalid. We propose nonparametric approaches to make point and interval predictions for landmark dates during the course of the trial. We obtain point predictions using the Kaplan-Meier estimator to extrapolate the survival probability into the future, selecting the time when the expected number of events is equal to the landmark number. To construct prediction intervals, we use a simulation strategy based on the Bayesian bootstrap. Monte Carlo results demonstrate the superiority of the nonparametric method when the assumptions underlying the parametric model are incorrect. We demonstrate the methods using data from a trial of immunotherapy of chronic granulomatous disease.

Granulomatous Disease, Chronic↗

PubMed1998

A nonparametric approach to a survival study with surrogate endpoints.

A nonparametric estimator for the joint distribution of a survival time and surrogate response time, which may occur earlier during follow-up, is presented. In the absence of the surrogate response variable, the estimator reduces to the Kaplan Meier nonparametric estimator for the survival time alone. The estimator derived in this paper is done so in a particular novel way using an exchangeable process (reinforced random walks) to model individual observations. The methodology introduced in the paper is readily extended to modelling multiple state processes.

Humans↗

PubMed2003

Nonparametric regression to the mean.

Available data may reflect a true but unknown random variable of interest plus an additive error, which is a nuisance. The problem in predicting the unknown random variable arises in many applied situations where measurements are contaminated with errors; it is known as the regression-to-the-mean problem. There exists a well known solution when both the distributions of the true underlying random variable and the contaminating errors are normal. This solution is given by the classical regression-to-the-mean formula, which has a data-shrinkage interpretation. We discuss the extension of this solution to cases where one or both of these distributions are unknown and demonstrate that the fully nonparametric case can be solved for the case of small contaminating errors. The resulting nonparametric regression-to-the-mean paradigm can be implemented by a straightforward data-sharpening algorithm that is based on local sample means. Asymptotic justifications and practical illustrations are provided.

Algorithms↗

PubMed2006

The imprecise science of evaluating scholarly performance: utilizing broad quality categories for an assessment of business and management journals.

In a growing number of countries, government-appointed assessment panels develop ranks on the basis of the quality of scholarly outputs to apportion budgets in recognition of evaluated performance and to justify public funds for future R&D activities. When business and management journals are being grouped in broad quality categories, a recent study has noted that this procedure was placing the same journals in essentially the same categories. Drawing on journal quality categorizations by several German- and English-speaking business departments and academic associations, the author performs nonparametric tests and correlations to analyze whether this claim can be substantiated. In particular, he examines the ability of broad quality categorizations to add value to governmental, administrative, and academic decision making by withstanding the criticism traditionally levied at research quality assessments.

Commerce↗

PubMed1998

Dependence of vancomycin clearance on renal function via regression and bootstrap methods.

BACKGROUND: Frequently, the estimation of vancomycin on the basis of renal function is too rough because the unknown parameters of a regression function between the vancomycin clearance (CL) and the creatinine clearance (ClCR) are based on small sample sizes. OBJECTIVE: In this study we aim to compare linear and nonlinear regression, spline interpolation and nonlinear kernel estimation for defining the relationship between measured Cl and ClCR. METHOD: We used data from published papers and appropriate numerical methods. The variability and accuracy of the estimated regression functions were determined from bootstrap methods and kernel density estimators. Tests to prove the usually assumed linearity of the regression were carried out and the influence of patient age and weight on Cl was determined. RESULTS: A linear relationship reported by several authors earlier has been determined as ClVAN = 0.763 ClCR + 2.715, (ml/min) (Cl = 0.011 ClCR + 0.055, (ml/min/ kg)). CONCLUSION: Nonparametric regression analysis shows that a nonlinear approximately parabolic function could fit the relationship between Cl and ClCR in the present case somewhat better than a linear function.

Anti-Bacterial Agents↗

PubMed1995

[The spectral analysis of heart rate variability. A comparative study between nonparametric and parametric spectral analysis in short series].

OBJECTIVE: to compare parametric (AR) and non parametric (FFT) spectral analysis results obtained in 512 beats series. INTERVENTIONS: 104 healthy subjects with normal physical examination and electrocardiogram were studied. The Ecg was recorded at rest, with controlled breathing at 15 cycles/min., and sampled at 300 Hz. The spectral VLF, LF and HF were calculated with FFT algorithm. For the same series, an auto-regressive analysis (AR) with optimized choice of the order of the model (AIC criterion) have been computed, VLF, LF and HF components were identified by AR spectral decomposition. RESULTS: In both groups, athletes and sedentary, there were no statistically differences between VLF, LF, HF and LF/HF spectral indices computed by the two methods. CONCLUSION: the results suggest that with controlled breathing it does not seems to exist any advantage in the use of AR spectral analysis to compute spectral components of heart rate variability, which is much more laborious that fixed bands non parametric FFT analysis.

Adolescent↗

PubMed2001

Two-trait-locus linkage analyses of asthma susceptibility.

A genome-wide search was conducted to identify chromosomal regions likely to harbor genes for asthma susceptibility. One hundred and twelve Caucasian families ascertained through a proband with a diagnosis of asthma by the Collaborative Study on the Genetics of Asthma (CSGA) were used for this search. Genotype data on 323 polymorphic markers were analyzed via parametric and nonparametric linkage analysis in an initial genome scan to identify potential asthma susceptibility region(s). The regions where hold or nonparametric linkage scores were greater than 2.0 were selected for further investigation using two-trait-locus linkage analysis models.

Adult↗

PubMed2005

Parametric and nonparametric bootstrap methods for meta-analysis.

In a meta-analysis, the unknown parameters are often estimated using maximum likelihood, and inferences are based on asymptotic theory. It is assumed that, conditional on study characteristics included in the model, the between-study distribution and the sampling distributions of the effect sizes are normal. In practice, however, samples are finite, and the normality assumption may be violated, possibly resulting in biased estimates and inappropriate standard errors. In this article, we propose two parametric and two nonparametric bootstrap methods that can be used to adjust the results of maximum likelihood estimation in meta-analysis and illustrate them with empirical data. A simulation study, with raw data drawn from normal distributions, reveals that the parametric bootstrap methods and one of the nonparametric methods are generally superior to the ordinary maximum likelihood approach but suffer from a bias/precision tradeoff. We recommend using one of these bootstrap methods, but without applying the bias correction.

Bias↗

PubMed2000

Abnormal LH pulsatility in women with hyperprolactinaemic amenorrhoea normalizes after bromocriptine treatment: deconvolution-based assessment.

OBJECTIVE: The present study examines the LH secretory process in hyperprolactinaemic women before, during and after bromocriptine therapy, using restrictive clinical selection criteria as well as improved methodological tools. PATIENTS AND DESIGN: Six women (aged 20-40 years) with microprolactinomas (mean +/- SE prolactin, PRL: 2478 +/- 427 mU/l, range: 1370-3800 mU/l) and four age- and sex-matched healthy controls were admitted to the study. After an overnight fast, all patients and controls had blood samples withdrawn at 10 minute intervals for 6 h (during saline infusion) from 0800 h to 1400 h to determine serum LH and PRL concentrations. After baseline evaluation, patients were treated with bromocriptine, which was started at a daily dose of 1.25 mg for 7 days; the dose was then increased to 2.5 mg daily for the next 7 days and subsequently to 2.5 mg twice daily. PRL levels were evaluated at weekly intervals after the beginning of bromocriptine therapy for the duration of the study. The 6 h pulsatility study was repeated on four patients during treatment at a time when PRL levels were decreased, although not normalized (PRL range: 450-1350 mU/l) and, on four patients, with the attainment of normal serum PRL levels (PRL < 450 mU/l) in the early follicular phase of the menstrual cycle (days 2-5). The LH instantaneous secretion rate was reconstructed by a nonparametric deconvolution method. In addition to pulse analysis made using the program DETECT, the evaluation of the secretion rate yielded the pulse frequency as well as the pulse amplitude distribution. RESULTS: Each time series was submitted to deconvolution analysis using a nonparametric method in order to estimate the instantaneous secretion rate (ISR). Hyperprolactinaemic patients had very few high-amplitude LH pulses above 0.2 IU/(l minutes) before treatment (average frequency: 0.83 +/- 0.40 pulses/6 h) and at the intermediate evaluation (0.25 +/- 0.25 pulses/6 h). In both cases, the pulse frequency was significantly lower than in controls (P < 0.05 and P < 0.01, respectively). When PRL was normalized, the number of high-amplitude LH pulses (4.25 +/- 1.03 pulses/6 h), became statistically different from the pulse number before (P < 0.01) and during (P < 0.01) therapy; in particular the pulse frequency after therapy rose to a level not statistically different from that in controls. CONCLUSION: The present study shows the presence of reduced LH pulsatility in hyperprolactinaemic women that recovers completely to within the physiological distribution when PRL levels are normalized by bromocriptine therapy.

Adult↗