Robust test method for time-course microarray experiments.

BACKGROUND: In a time-course microarray experiment, the expression level for each gene is observed across a number of time-points in order to characterize the temporal trajectories of the gene-expression profiles. For many of these experiments, the scientific aim is the identification of genes for which the trajectories depend on an experimental or phenotypic factor. There is an extensive recent body of literature on statistical methodology for addressing this analytical problem. Most of the existing methods are based on estimating the time-course trajectories using parametric or non-parametric mean regression methods. The sensitivity of these regression methods to outliers, an issue that is well documented in the statistical literature, should be of concern when analyzing microarray data. RESULTS: In this paper, we propose a robust testing method for identifying genes whose expression time profiles depend on a factor. Furthermore, we propose a multiple testing procedure to adjust for multiplicity. CONCLUSIONS: Through an extensive simulation study, we will illustrate the performance of our method. Finally, we will report the results from applying our method to a case study and discussing potential extensions.

Impact of a Point-of-Care Rapid Influenza Test on Antibiotic Prescribing Patterns in Southern Sri Lanka

Background: Acute febrile respiratory illnesses, including influenza, account for a large proportion of ambulatory care visits worldwide. In the developed world, these encounters commonly result in unwarranted antibiotic prescriptions; data from more resource-limited settings are lacking. The purpose of this study was to describe the epidemiology of influenza among outpatients in southern Sri Lanka and to determine if access to rapid influenza test results was associated with decreased antibiotic prescriptions.

Methods: In this pretest- posttest study, consecutive patients presenting from March 2013- April 2014 to the Outpatient Department of the largest tertiary care hospital in southern Sri Lanka were surveyed for influenza-like illness (ILI). Patients meeting World Health Organization criteria for ILI-- acute onset of fever ≥38.0°C and cough in the prior 7 days--were enrolled. Consenting patients were administered a structured questionnaire, physical examination, and nasal/nasopharyngeal sampling. Rapid influenza A/B testing (Veritor System, Becton Dickinson) was performed on all patients, but test results were only released to patients and clinicians during the second phase of the study (December 2013- April 2014).

Results: We enrolled 397 patients with ILI, with 217 (54.7%) adults ≥12 years and 188 (47.4%) females. A total of 179 (45.8%) tested positive for influenza by rapid testing, with April- July 2013 and September- November 2013 being the periods with the highest proportion of ILI due to influenza. A total of 310 (78.1%) patients with ILI received a prescription for an antibiotic from their outpatient provider. The proportion of patients prescribed antibiotics decreased from 81.4% in the first phase to 66.3% in the second phase (p=.005); among rapid influenza-positive patients, antibiotic prescriptions decreased from 83.7% in the first phase to 56.3% in the second phase (p=.001). On multivariable analysis, having a positive rapid influenza test available to clinicians was associated with decreased antibiotic use (OR 0.20, 95% CI 0.05- 0.82).

Conclusions: Influenza virus accounted for almost 50% of acute febrile respiratory illness in this study, but most patients were prescribed antibiotics. Providing rapid influenza test results to clinicians was associated with fewer antibiotic prescriptions, but overall prescription of antibiotics remained high. In this developing country setting, a multi-faceted approach that includes improved access to rapid diagnostic tests may help decrease antibiotic use and combat antimicrobial resistance.

CD4 enumeration technologies: a systematic review of test performance for determining eligibility for antiretroviral therapy.

BACKGROUND: Measurement of CD4+ T-lymphocytes (CD4) is a crucial parameter in the management of HIV patients, particularly in determining eligibility to initiate antiretroviral treatment (ART). A number of technologies exist for CD4 enumeration, with considerable variation in cost, complexity, and operational requirements. We conducted a systematic review of the performance of technologies for CD4 enumeration. METHODS AND FINDINGS: Studies were identified by searching electronic databases MEDLINE and EMBASE using a pre-defined search strategy. Data on test accuracy and precision included bias and limits of agreement with a reference standard, and misclassification probabilities around CD4 thresholds of 200 and 350 cells/μl over a clinically relevant range. The secondary outcome measure was test imprecision, expressed as % coefficient of variation. Thirty-two studies evaluating 15 CD4 technologies were included, of which less than half presented data on bias and misclassification compared to the same reference technology. At CD4 counts <350 cells/μl, bias ranged from -35.2 to +13.1 cells/μl while at counts >350 cells/μl, bias ranged from -70.7 to +47 cells/μl, compared to the BD FACSCount as a reference technology. Misclassification around the threshold of 350 cells/μl ranged from 1-29% for upward classification, resulting in under-treatment, and 7-68% for downward classification resulting in overtreatment. Less than half of these studies reported within laboratory precision or reproducibility of the CD4 values obtained. CONCLUSIONS: A wide range of bias and percent misclassification around treatment thresholds were reported on the CD4 enumeration technologies included in this review, with few studies reporting assay precision. The lack of standardised methodology on test evaluation, including the use of different reference standards, is a barrier to assessing relative assay performance and could hinder the introduction of new point-of-care assays in countries where they are most needed.

Application of a rank-based genetic association test to age-at-onset data from the Collaborative Study on the Genetics of Alcoholism study.

Association studies of quantitative traits have often relied on methods in which a normal distribution of the trait is assumed. However, quantitative phenotypes from complex human diseases are often censored, highly skewed, or contaminated with outlying values. We recently developed a rank-based association method that takes into account censoring and makes no distributional assumptions about the trait. In this study, we applied our new method to age-at-onset data on ALDX1 and ALDX2. Both traits are highly skewed (skewness > 1.9) and often censored. We performed a whole genome association study of age at onset of the ALDX1 trait using Illumina single-nucleotide polymorphisms. Only slightly more than 5% of markers were significant. However, we identified two regions on chromosomes 14 and 15, which each have at least four significant markers clustering together. These two regions may harbor genes that regulate age at onset of ALDX1 and ALDX2. Future fine mapping of these two regions with densely spaced markers is warranted.

Component-wise gradient boosting and false discovery control in survival analysis with high-dimensional covariates.

MOTIVATION: Technological advances that allow routine identification of high-dimensional risk factors have led to high demand for statistical techniques that enable full utilization of these rich sources of information for genetics studies. Variable selection for censored outcome data as well as control of false discoveries (i.e. inclusion of irrelevant variables) in the presence of high-dimensional predictors present serious challenges. This article develops a computationally feasible method based on boosting and stability selection. Specifically, we modified the component-wise gradient boosting to improve the computational feasibility and introduced random permutation in stability selection for controlling false discoveries. RESULTS: We have proposed a high-dimensional variable selection method by incorporating stability selection to control false discovery. Comparisons between the proposed method and the commonly used univariate and Lasso approaches for variable selection reveal that the proposed method yields fewer false discoveries. The proposed method is applied to study the associations of 2339 common single-nucleotide polymorphisms (SNPs) with overall survival among cutaneous melanoma (CM) patients. The results have confirmed that BRCA2 pathway SNPs are likely to be associated with overall survival, as reported by previous literature. Moreover, we have identified several new Fanconi anemia (FA) pathway SNPs that are likely to modulate survival of CM patients. AVAILABILITY AND IMPLEMENTATION: The related source code and documents are freely available at https://sites.google.com/site/bestumich/issues. CONTACT: yili@umich.edu.

Tuberculin skin test versus blood immunologic diagnosis of latent mycobacterium tuberclosis infection among old subjects

info:eu-repo/semantics/published

Contribution of a heparin-binding haemagglutinin interferon-gamma release assay to the detection of Mycobacterium tuberculosis infection in HIV-infected patients: comparison with the tuberculin skin test and the QuantiFERON-TB Gold In-tube.

The screening and treatment of latent tuberculosis (TB) infection reduces the risk of progression to active disease and is currently recommended for HIV-infected patients. The aim of this study is to evaluate, in a low TB incidence setting, the potential contribution of an interferon-gamma release assay in response to the mycobacterial latency antigen Heparin-Binding Haemagglutinin (HBHA-IGRA), to the detection of Mycobacterium tuberculosis infection in HIV-infected patients.

Análisis estadístico de un test de conocimientos previos de matemáticas para ingresantes universitarios

En este trabajo presentamos un análisis estadístico del Test de Conocimientos Previos de Matemáticas (TCPM) diseñado para medir el estado inicial de destrezas y conocimientos básicos en matemáticas de los alumnos ingresantes a carreras científico-tecnológicas de la Facultad de Ciencias Físico, Matemáticas y Naturales de la Universidad Nacional de San Luis. El objetivo de la investigación está centrado en observar el diagnóstico utilizado, con miras a una eventual utilización posterior. Para determinar la bondad de la prueba realizamos un análisis de la calidad, discriminación e índice de dificultad de los ítems, así como de la validez y confiabilidad del diagnóstico, para este análisis estadístico empleamos los programas TestGraf y SPSS. El test se aplicó a 698 estudiantes ingresantes a la Universidad en el ciclo lectivo 2002. De la investigación pudimos inferir que el diagnóstico resultó: difícil para la población de aplicación; de confiabilidad aceptable, y de buena calidad de items, con variada dificultad y aceptable discriminación.

Simulating one of the CIB W14 round robin test cases using the SMARTFIRE fire field model

Numerical predictions produced by the SMARTFIRE fire field model are compared with experimental data. The predictions consist of gas temperatures at several locations within the compartment over a 60 min period. The test fire, produced by a burning wood crib attained a maximum heat release rate of approximately 11MW. The fire is intended to represent a nonspreading fire (i.e. single fuel source) in a moderately sized ventilated room. The experimental data formed part of the CIB Round Robin test series. Two simulations are produced, one involving a relatively coarse mesh and the other with a finer mesh. While the SMARTFIRE simulations made use of a simple volumetric heat release rate model, both simulations were found capable of reproducing the overall qualitative results. Both simulations tended to overpredict the measured temperatures. However, the finer mesh simulation was better able to reproduce the qualitative features of the experimental data. The maximum recorded experimental temperature (12141C after 39 min) was over-predicted in the fine mesh simulation by 12%. (C) 2001 Elsevier Science Ltd. All rights reserved.

Modeling and experiments on an isothermal fatigue test for solder joints

This paper investigates an isothermal fatigue test for solder joints developed at the NPL. The test specimen is a lap joint between two copper arms. During the test the displacement at the ends of the copper are controlled and the force measured. The modeling results in the paper show that the displacement across the solder joint is not equal to the displacement applied at the end of the specimen. This is due to deformation within the copper arms. A method is described to compensate for this difference. The strain distribution in the solder was determined by finite element analysis and compared to the distribution generated by a theoretical 'ideal' test which generates an almost pure shear mode in the solder. By using a damage-based constitutive law the shape of the crack generated in the specimen has been predicted for both the actual test and the ideal pure shear test. Results from the simulations are also compared with experimental data using SnAgCu solder.

Assessment of the impact of computed and measured fire environments on building evacuation using bench and real scale test data

This study investigates the use of computer modelled versus directly experimentally determined fire hazard data for assessing survivability within buildings using evacuation models incorporating Fractionally Effective Dose (FED) models. The objective is to establish a link between effluent toxicity, measured using a variety of small and large scale tests, and building evacuation. For the scenarios under consideration, fire simulation is typically used to determine the time non-survivable conditions develop within the enclosure, for example, when smoke or toxic effluent falls below a critical height which is deemed detrimental to evacuation or when the radiative fluxes reach a critical value leading to the onset of flashover. The evacuation calculation would the be used to determine whether people within the structure could evacuate before these critical conditions develop.

Droplet oscillations in high gradient magnetic field

In high intensity and high gradient magnetic fields the volumetric force on diamagnetic material, such as water, leads to conditions very similar to microgravity in a terrestrial laboratory. In principle, this opens the possibility to determine material properties of liquid samples without wall contact, even for electrically non-conducting materials. In contrast, AC field levitation is used for conductors, but then terrestrial conditions lead to turbulent flow driven by Lorentz forces. DC field damping of the flow is feasible and indeed practiced to allow property measurements. However, the AC/DC field combination acts preferentially on certain oscillation modes and leads to a shift in the droplet oscillation spectrum.What is the cause? A nonlinear spectral numerical model is presented, to address these problems

Droplet oscillations in high gradient static magnetic field

In high intensity and high gradient magnetic fields the volumetric force on diamagnetic material, such as water, leads to conditions very similar to microgravity in a terrestrial laboratory. In principle, this opens the possibility to determine material properties of liquid samples without wall contact, even for electrically non-conducting materials. In contrast, AC field levitation is used for conductors, but then terrestrial conditions lead to turbulent flow driven by Lorentz forces. DC field damping of the flow is feasible and indeed practiced to allow property measurements. However, the AC/DC field combination acts preferentially on certain oscillation modes and leads to a shift in the droplet oscillation spectrum.What is the cause? A nonlinear spectral numerical model is presented, to address these problems.