Estimating the Area under a Receiver Operating Characteristic Curve For Repeated Measures Design

The receiver operating characteristic (ROC) curve is widely used for diagnosing as well as for judging the discrimination ability of different statistical models. Although theories about ROC curves have been established and computation methods and computer software are available for cross-sectional design, limited research for estimating ROC curves and their summary statistics has been done for repeated measure designs, which are useful in many applications, such as biological, medical and health services research. Furthermore, there is no published statistical software available that can generate ROC curves and calculate summary statistics of the area under a ROC curve for data from a repeated measures design. Using generalized linear mixed model (GLMM), we estimate the predicted probabilities of the positivity of a disease or condition, and the estimated probability is then used as a bio-marker for constructing the ROC curve and computing the area under the curve. The area under a ROC curve is calculated using the Wilcoxon non-parametric approach by comparing the predicted probability of all discordant pairs of observations. The ROC curve is constructed by plotting a series of pairs of true positive rate (sensitivity) and false positive rate (1- specificity) calculated from varying cuts of positivity escalated by increments of 0.005 in predicted probability. The computation software is written in SAS/IML/MACRO v8 and can be executed in any computer that has a working SAS v8 system with SAS/IML/MACRO.

Sample Size Calculation and Power Analysis of Time-Averaged Difference

Little research has been done on sample size and power analysis under repeated measures design. With detailed derivation, we have shown sample size calculation and power analysis equations for timeaveraged difference to allow unequal sample sizes between two groups for both continuous and binary measures and explored the relative importance of number of unique subjects and number of repeated measurements within each subject on statistical power through simulation

Estimating the Area under a Receiver Operating Characteristic Curve For Repeated Measures Design

The receiver operating characteristic (ROC) curve is widely used for diagnosing as well as for judging the discrimination ability of different statistical models. Although theories about ROC curves have been established and computation methods and computer software are available for cross-sectional design, limited research for estimating ROC curves and their summary statistics has been done for repeated measure designs, which are useful in many applications, such as biological, medical and health services research. Furthermore, there is no published statistical software available that can generate ROC curves and calculate summary statistics of the area under a ROC curve for data from a repeated measures design. Using generalized linear mixed model (GLMM), we estimate the predicted probabilities of the positivity of a disease or condition, and the estimated probability is then used as a bio-marker for constructing the ROC curve and computing the area under the curve. The area under a ROC curve is calculated using the Wilcoxon non-parametric approach by comparing the predicted probability of all discordant pairs of observations. The ROC curve is constructed by plotting a series of pairs of true positive rate (sensitivity) and false positive rate (1- specificity) calculated from varying cuts of positivity escalated by increments of 0.005 in predicted probability. The computation software is written in SAS/IML/MACRO v8 and can be executed in any computer that has a working SAS v8 system with SAS/IML/MACRO

The Influences of Combined Distortions on Fan Performance

Combined distortions negatively affect the aerodynamic stability of fans, but previous studies have limitations. The 3D CFD method was used to calculate the aerodynamic stability of fans under the total pressure and swirl distortion, total temperature and swirl distortion, and total pressure and total temperature distortion in the work. Rotor 67 was taken as the research object. According to the calculation results, the influences of variable distortion parameters on fan performance under combined distortions were summarized to establish the functional relationship between stability margin losses and distortion parameters

Development of In Vitro Denture Biofilm Models for Halitosis Related Bacteria and Their Application in Testing the Efficacy of Antimicrobial Agents

Objective: Since dentures can serve as a reservoir for halitosis-causing oral bacteria, halitosis development is a concern for denture wearers. In this study, we surveyed the prevalence of four selected halitosis-related species (Fusobacterium nucleatum, Tannerella forsythia, Veillonella atypica and Klebsiella pneumoniae) in clinical denture plaque samples, and developed denture biofilm models for these species in vitro to facilitate assessment of antimicrobial treatment efficacy. Design: Denture plaque from ten healthy and ten denture stomatitis patients was screened for the presence of aforementioned four species by PCR. Biofilm formation by these halitosis-associated species on the surfaces of denture base resin (DBR) discs was evaluated by crystal violet staining and confocal laser scanning microscopy. The efficacy of denture cleanser treatment on these mono-species biofilms was evaluated by colony counting. Results: 80% of the subjects in the denture stomatitis group and 60% in the healthy group contained at least one of the targeted halitosis-related species in their denture plaque. All halitosis species tested were able to form biofilms on DBR disc surfaces to varying degrees. These in vitro mono-species resin biofilm models were used to evaluate the efficacy of denture cleansers, which exhibited differential efficacies. When forming biofilms on resin surfaces, the halitosis-related species displayed enhanced resistance to denture cleansers compared with their planktonic counterparts. Conclusion: The four selected halitosis-related bacterial species examined in this study are present on the majority of dentures. The mono-species biofilm models established on DBR discs for these species are an efficient screening tool for dental product evaluation

Randomized controlled trial of a coordinated care intervention to improve risk factor control after stroke or transient ischemic attack in the safety net: Secondary stroke prevention by Uniting Community and Chronic care model teams Early to End Disparities (SUCCEED).

BackgroundRecurrent strokes are preventable through awareness and control of risk factors such as hypertension, and through lifestyle changes such as healthier diets, greater physical activity, and smoking cessation. However, vascular risk factor control is frequently poor among stroke survivors, particularly among socio-economically disadvantaged blacks, Latinos and other people of color. The Chronic Care Model (CCM) is an effective framework for multi-component interventions aimed at improving care processes and outcomes for individuals with chronic disease. In addition, community health workers (CHWs) have played an integral role in reducing health disparities; however, their effectiveness in reducing vascular risk among stroke survivors remains unknown. Our objectives are to develop, test, and assess the economic value of a CCM-based intervention using an Advanced Practice Clinician (APC)-CHW team to improve risk factor control after stroke in an under-resourced, racially/ethnically diverse population.Methods/designIn this single-blind randomized controlled trial, 516 adults (≥40 years) with an ischemic stroke, transient ischemic attack or intracerebral hemorrhage within the prior 90 days are being enrolled at five sites within the Los Angeles County safety-net setting and randomized 1:1 to intervention vs usual care. Participants are excluded if they do not speak English, Spanish, Cantonese, Mandarin, or Korean or if they are unable to consent. The intervention includes a minimum of three clinic visits in the healthcare setting, three home visits, and Chronic Disease Self-Management Program group workshops in community venues. The primary outcome is blood pressure (BP) control (systolic BP <130 mmHg) at 1 year. Secondary outcomes include: (1) mean change in systolic BP; (2) control of other vascular risk factors including lipids and hemoglobin A1c, (3) inflammation (C reactive protein [CRP]), (4) medication adherence, (5) lifestyle factors (smoking, diet, and physical activity), (6) estimated relative reduction in risk for recurrent stroke or myocardial infarction (MI), and (7) cost-effectiveness of the intervention versus usual care.DiscussionIf this multi-component interdisciplinary intervention is shown to be effective in improving risk factor control after stroke, it may serve as a model that can be used internationally to reduce race/ethnic and socioeconomic disparities in stroke in resource-constrained settings.Trial registrationClinicalTrials.gov Identifier NCT01763203

Randomized controlled trial of a coordinated care intervention to improve risk factor control after stroke or transient ischemic attack in the safety net: Secondary stroke prevention by Uniting Community and Chronic care model teams Early to End Disparities (SUCCEED)

BACKGROUND: Recurrent strokes are preventable through awareness and control of risk factors such as hypertension, and through lifestyle changes such as healthier diets, greater physical activity, and smoking cessation. However, vascular risk factor control is frequently poor among stroke survivors, particularly among socio-economically disadvantaged blacks, Latinos and other people of color. The Chronic Care Model (CCM) is an effective framework for multi-component interventions aimed at improving care processes and outcomes for individuals with chronic disease. In addition, community health workers (CHWs) have played an integral role in reducing health disparities; however, their effectiveness in reducing vascular risk among stroke survivors remains unknown. Our objectives are to develop, test, and assess the economic value of a CCM-based intervention using an Advanced Practice Clinician (APC)-CHW team to improve risk factor control after stroke in an under-resourced, racially/ethnically diverse population. METHODS/DESIGN: In this single-blind randomized controlled trial, 516 adults (≥40 years) with an ischemic stroke, transient ischemic attack or intracerebral hemorrhage within the prior 90 days are being enrolled at five sites within the Los Angeles County safety-net setting and randomized 1:1 to intervention vs usual care. Participants are excluded if they do not speak English, Spanish, Cantonese, Mandarin, or Korean or if they are unable to consent. The intervention includes a minimum of three clinic visits in the healthcare setting, three home visits, and Chronic Disease Self-Management Program group workshops in community venues. The primary outcome is blood pressure (BP) control (systolic BP <130 mmHg) at 1 year. Secondary outcomes include: (1) mean change in systolic BP; (2) control of other vascular risk factors including lipids and hemoglobin A1c, (3) inflammation (C reactive protein [CRP]), (4) medication adherence, (5) lifestyle factors (smoking, diet, and physical activity), (6) estimated relative reduction in risk for recurrent stroke or myocardial infarction (MI), and (7) cost-effectiveness of the intervention versus usual care. DISCUSSION: If this multi-component interdisciplinary intervention is shown to be effective in improving risk factor control after stroke, it may serve as a model that can be used internationally to reduce race/ethnic and socioeconomic disparities in stroke in resource-constrained settings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01763203

Temporally gene knockout using heat shock–inducible genome‐editing system in plants

Abstract Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR‐associated nuclease 9 (Cas9) has emerged as a powerful tool to generate targeted loss‐of‐function mutations for functional genomic studies. As a next step, tools to generate genome modifications in a spatially and temporally precise manner will enable researchers to further dissect gene function. Here, we present two heat shock–inducible genome‐editing (IGE) systems that efficiently edit target genes when the system is induced, thus allowing us to target specific developmental stages. For this conditional editing system, we chose the natural heat‐inducible promoter from heat‐shock protein 18.2 (HSP18.2) from Arabidopsis thaliana and the synthetic heat–inducible promoter heat shock–response element HSE‐COR15A to drive the expression of Cas9. We tested these two IGE systems in Arabidopsis using cyclic or continuous heat‐shock treatments at the seedling and bolting stages. A real‐time quantitative polymerase chain reaction analysis revealed that the HSP18.2 IGE system exhibited higher Cas9 expression levels than the HSE‐COR15A IGE system upon both cyclic and continuous treatments. By targeting brassinosteroid‐insensitive 1 (BRI1) and phytoene desaturase (PDS), we demonstrate that both cyclic and continuous heat inductions successfully activated the HSP18.2 IGE system at the two developmental stages, resulting in highly efficient targeted mutagenesis and clear phenotypic outcomes. By contrast, the HSE‐COR15A IGE system was only induced at the seedling stage and was less effective than the HSP18.2 IGE system in terms of mutagenesis frequencies. The presented heat shock–IGE systems can be conditionally induced to efficiently inactivate genes at any developmental stage and are uniquely suited for the dissection and systematic characterization of essential genes