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At least 1,477 records · Page 82Linked to original sources
PubMed2005

Differential and trajectory methods for time course gene expression data.

MOTIVATION: The issue of high dimensionality in microarray data has been, and remains, a hot topic in statistical and computational analysis. Efficient gene filtering and differentiation approaches can reduce the dimensions of data, help to remove redundant genes and noises, and highlight the most relevant genes that are major players in the development of certain diseases or the effect of drug treatment. The purpose of this study is to investigate the efficiency of parametric (including Bayesian and non-Bayesian, linear and non-linear), non-parametric and semi-parametric gene filtering methods through the application of time course microarray data from multiple sclerosis patients being treated with interferon-beta-1a. The analysis of variance with bootstrapping (parametric), class dispersion (semi-parametric) and Pareto (non-parametric) with permutation methods are presented and compared for filtering and finding differentially expressed genes. The Bayesian linear correlated model, the Bayesian non-linear model the and non-Bayesian mixed effects model with bootstrap were also developed to characterize the differential expression patterns. Furthermore, trajectory-clustering approaches were developed in order to investigate the dynamic patterns and inter-dependency of drug treatment effects on gene expression. RESULTS: Results show that the presented methods performed significant differently but all were adequate in capturing a small number of the potentially relevant genes to the disease. The parametric method, such as the mixed model and two Bayesian approaches proved to be more conservative. This may because these methods are based on overall variation in expression across all time points. The semi-parametric (class dispersion) and non-parametric (Pareto) methods were appropriate in capturing variation in expression from time point to time point, thereby making them more suitable for investigating significant monotonic changes and trajectories of changes in gene expressions in time course microarray data. Also, the non-linear Bayesian model proved to be less conservative than linear Bayesian correlated growth models to filter out the redundant genes, although the linear model showed better fit than non-linear model (smaller DIC). We also report the trajectories of significant genes-since we have been able to isolate trajectories of genes whose regulations appear to be inter-dependent.

Computer Simulation↗
PubMed2005

Highly consistent patterns for inherited human diseases at the molecular level.

Over 1600 mammalian genes are known to cause an inherited disorder, when subjected to one or more mutations. These disease genes represent a unique resource for the identification and quantification of relationships between phenotypic attributes of a disease and the molecular features of the associated disease genes, including their ascribed annotated functional classes and expression patterns. Such analyses can provide a more global perspective and a deeper understanding of the probable causes underlying human hereditary diseases. In this perspective and critical view of disease genomics, we present a comparative analysis of genes reported to cause inherited diseases in humans in terms of their causative effects on physiology, their genetics and inheritance modes, the functional processes they are involved in and their expression profiles across a wide spectrum of tissues. Our analysis reveals that there are more extensive correlations between these attributes of genetic disease genes than previously appreciated. For instance, the functional pattern of genes causing dominant and recessive diseases is markedly different. Also, the function of the genes and their expression correlate with the type of disease they cause when mutated. The results further indicate that a comparative genomics approach for the analysis of genes linked to human genetic diseases will facilitate the elucidation of the underlying molecular and cellular mechanisms.

Biomarkers↗
PubMed2005

One- and two-sample nonparametric inference procedures in the presence of a mixture of independent and dependent censoring.

In survival analysis, the event time T is often subject to dependent censorship. Without assuming a parametric model between the failure and censoring times, the parameter Theta of interest, for example, the survival function of T, is generally not identifiable. On the other hand, the collection Omega of all attainable values for Theta may be well defined. In this article, we present nonparametric inference procedures for Omega in the presence of a mixture of dependent and independent censoring variables. By varying the criteria of classifying censoring to the dependent or independent category, our proposals can be quite useful for the so-called sensitivity analysis of censored failure times. The case that the failure time is subject to possibly dependent interval censorship is also discussed in this article. The new proposals are illustrated with data from two clinical studies on HIV-related diseases.

Anti-HIV Agents↗
PubMed2000

The effect of interferon beta-1b treatment on MRI measures of cerebral atrophy in secondary progressive multiple sclerosis. European Study Group on Interferon beta-1b in secondary progressive multiple sclerosis.

The recently completed European trial of interferon beta-1b (IFNbeta-1b) in patients with secondary progressive multiple sclerosis (SP multiple sclerosis) has given an opportunity to assess the impact of treatment on cerebral atrophy using serial MRI. Unenhanced T(1)-weighted brain imaging was acquired in a subgroup of 95 patients from five of the European centres; imaging was performed at 6-month intervals from month 0 to month 36. A blinded observer measured cerebral volume on four contiguous 5 mm cerebral hemisphere slices at each time point, using an algorithm with a high level of reproducibility and automation. There was a significant and progressive reduction in cerebral volume in both placebo and treated groups, with a mean reduction of 3.9 and 2.9%, respectively, by month 36 (P = 0.34 between groups). Exploratory subgroup analyses indicated that patients without gadolinium (Gd) enhancement at the baseline had a greater reduction of cerebral volume in the placebo group (mean reduction at month 36: placebo 5.1%, IFNbeta-1b 1.8%, P < 0.05) whereas those with Gd-enhancing lesions showed a trend to greater reduction of cerebral volume if the patient was on IFNbeta-1b (placebo 2.6%, IFNbeta-1b 3.7%; P > 0.05). These results are consistent with ongoing tissue loss in both arms of this study of secondary progressive multiple sclerosis. This finding is concordant with previous observations that disease progression, although delayed, is not halted by IFNbeta. The different pattern seen in patients with and without baseline gadolinium enhancement suggests that part of the cerebral volume reduction observed in IFNbeta-treated patients may be due to the anti-inflammatory/antioedematous effect of the drug. Longer periods of observation and larger groups of patients may be needed to detect the effects of treatment on cerebral atrophy in this population of patients with advanced disease.

Adult↗
PubMed1999

Properties of the geometrically averaged ratio, an alternative standardized measure.

In epidemiology, the comparative mortality figure and the standardized mortality ratio are standardized measures in common use. Both are weighted averages of rate ratios (or observed/expected death count ratios) on the arithmetic scale. I propose a new standardized measure, the geometrically averaged ratio (GAR), which is defined through simple averaging on the logarithmic scale. I show that, in addition to providing a valid comparison between populations, the geometrically averaged ratio possesses the following desirable properties: (1) invertibility and invariance of standardized sex ratios and (2) interpopulational comparability with different standards.

Epidemiologic Methods↗
PubMed1976

The use of test results from ASA workshops to evaluate workshop effectiveness.

Results of tests given to participants in six American Society of Anesthesiologists workshops were analyzed to detemine whether attendance at the workshops increased the participants' scores on sequential tests. Those who attended the workshops took the same test prior to, immediately after, and three months after the workshop. Two control groups of anesthesiologists took the tests in the same time sequence for comparison. Both workshop and control groups increased their scores with each successive test. In only one instance did those who attended the workshop improve their scores significantly more than did the control group. Because of difficulties inherent in designing valid and reliable tests, further development of the testing technique currently used at the workshops is necessary to make it a useful measure of workshop effectiveness.

Anesthesiology↗
PubMed2002

A thoracostomy tube guideline improves management efficiency in trauma patients.

BACKGROUND: Thoracostomy tube (TT) placement constitutes primary treatment for traumatic hemopneumothorax. Practice patterns vary widely, and criteria for management and removal remain poorly defined. In this cohort study, we examined the impact of implementation of a practice guideline (PG) on improving management efficiency of thoracostomy tube. METHODS: We developed a PG aimed at standardizing the management of TTs in critically ill patients admitted to a Level I trauma center. During the 9-month period before (Pre-PG) and 3 months after (Post-PG) implementation, practice parameters including prophylactic antibiotics, duration of TT therapy, preremoval chest radiographs with associated charges, and complications were evaluated. Differences between groups were assessed by Mann-Whitney rank sum and chi(2) with Yates correction. RESULTS: There were 61 patients, 14 in the Pre-PG group and 47 in the Post-PG group. The groups were matched in age and Injury Severity Scores. The Post-PG cohort averaged 3 fewer days of TT therapy. After implementation of the PG, 21 patients did not have preremoval chest radiography, representing a $3000 reduction in radiology fees. Complication rates (retained pneumothorax, hemothorax, and empyema) were not different between the two groups. CONCLUSION: Implementation of a thoracostomy tube practice guideline was associated with improved management efficiency in trauma patients.

Adolescent↗
PubMedDate not supplied

Fidelity to a 12-week structured medication adherence intervention in patients with HIV.

BACKGROUND: Researchers have been conducting efficacy and effectiveness studies on interventions that address medication-taking behavior in patients with HIV infection. However, they also must examine the fidelity to the research protocol for the delivery of the intervention. OBJECTIVES: The aims of this study were to determine the level of fidelity to each of the specified end points (number of intervention sessions, session duration, number of telephone calls per session, the length of time between sessions, sessions with multiple interventions, and attrition from the intervention protocol) in the delivery of the 12-week, nurse-delivered, structured telephone intervention designed to improve medication adherence and to determine the factors (race, gender, and socioeconomic status) related to participation in the intervention. METHODS: This descriptive correlational study was a substudy of a larger randomized clinical trial (N = 200) testing the effectiveness of a 12-week nurse-delivered intervention designed to improve medication adherence to antiretroviral medications in persons with HIV infection. The Intervention Tracking Form was used to collect data on all intervention delivery end points during the delivery of the structured intervention. A sociodemographic questionnaire was used to collect the sociodemographic characteristics of the sample. RESULTS: Two thirds of the sample (n = 66) were male, and slightly more than half were White. The average age was 39.68 (SD = 7.98) years. The average number of intervention sessions delivered was 8.1 (SD = 4.07). Participants were more likely to receive the first five intervention sessions (n = 77, 77.8%), and 21 (21.2%) dropped out of treatment before it was completed. Nearly one quarter (n = 24, 24.2%) of the sample had doubled-up interventions. Intervention sessions lasted, on average, 11.3 min. Typically, more than one telephone call was needed before the participant was reached (M = 2.2). The mean number of days between sessions was 11.5 days. Women were more likely to have doubled-up interventions (p = .036). There was a marginally significant difference (p = .075) in the number of sessions received between the Whites and non-Whites: Whites (M = 8.8, SD = 3.9) received slightly more sessions compared with non-Whites (M = 7.24, SD = 4.2). When examining the interaction effects between the demographic factors considered, a race-by-income effect was observed for the mean number of attempts to contact the participant (p = .044). DISCUSSION: These results demonstrate a lack of fidelity to the research intervention protocol. Factors beyond the researchers' control may have influenced fidelity to the intervention protocol.

Adult↗
PubMed1980

Clinical comparison of the (polymacon) spin-cast hydrogel contact lens to the (polymacon) lathe-cut hydrogel lenses.

The purpose of this study was to compare the clinical acceptability of polymacon spin-cast to polymacon lathe-cut hydrophilic contact lenses. Ten patients successfully wearing polymacon spin-cast lenses were studied. Each patient had one eye refitted with polymacon lathe-cut lenses. Comparison of the two types of lenses was then made. Objective evaluation included centration, movement, visual acuity, and over-refraction. Subjective criteria were based on patient comfort and stability and quality of vision. Results indicate that lathe-cut lenses can be just as clinically satisfactory as the spincast ones.

Clinical Trials as Topic↗