Statistical assessment of the prognostic and the predictive value of biomarkers-A biomarker assessment framework with applications to traumatic brain injury biomarker studies.

Studies that investigate the performance of prognostic and predictive biomarkers are commonplace in medicine. Evaluating the performance of biomarkers is challenging in traumatic brain injury (TBI) and other conditions when both the time factor (i.e.

On optimal biomarker cutoffs accounting for misclassification costs in diagnostic trilemmas with applications to pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is the most deadly cancer and currently there is strong clinical interest in novel biomarkers that contribute to its early detection. Assessing appropriately the accuracy of such biomarkers is a crucial issue and often one needs to take into account that many assays include biospecimens of individuals coming from three groups: healthy, chronic pancreatitis, and PDAC. The ROC surface is an appropriate tool for assessing the overall accuracy of a marker employed under such trichotomous settings.

A Novel Approach to Image Recoloring for Color Vision Deficiency.

In this paper, a novel method to modify color images for the protanopia and deuteranopia color vision deficiencies is proposed. The method admits certain criteria, such as preserving image naturalness and color contrast enhancement. Four modules are employed in the process.

The length of the receiver operating characteristic curve and the two cutoff Youden index within a robust framework for discovery, evaluation, and cutoff estimation in biomarker studies involving improper receiver operating characteristic curves.

During the early stage of biomarker discovery, high throughput technologies allow for simultaneous input of thousands of biomarkers that attempt to discriminate between healthy and diseased subjects. In such cases, proper ranking of biomarkers is highly important. Common measures, such as the area under the receiver operating characteristic (ROC) curve (AUC), as well as affordable sensitivity and specificity levels, are often taken into consideration.

Survival estimation through the cumulative hazard with monotone natural cubic splines using convex optimization-the HCNS approach.

Background And Objectives: In survival analysis both the Kaplan-Meier estimate and the Cox model enjoy a broad acceptance. We present an improved spline-based survival estimate and offer a fully automated software for its implementation. We explore the use of natural cubic splines that are constrained to be monotone.

Estimation of smooth ROC curves for biomarkers with limits of detection.

Protein biomarkers found in plasma are commonly used for cancer screening and early detection. Measurements obtained by such markers are often based on different assays that may not support detection of accurate measurements due to a limit of detection. The ROC curve is the most popular statistical tool for the evaluation of a continuous biomarker.

Smooth ROC curves and surfaces for markers subject to a limit of detection using monotone natural cubic splines.

The use of ROC curves in evaluating a continuous or ordinal biomarker for the discrimination of two populations is commonplace. However, in many settings, marker measurements above or below a certain value cannot be obtained. In this paper, we study the construction of a smooth ROC curve (or surface in the case of three populations) when there is a lower or upper limit of detection.

Recursive hierarchic segmentation analysis of bone mineral density changes on digital panoramic images.

Objective: The aim of this study was to demonstrate that histogram analysis and mathematical modeling of digital panoramic images (DPIs) processed using recursive hierarchic segmentation (RHSEG) discriminates normal, osteopenic, and osteoporotic cancellous bone.

Study Design: Forty-seven DPIs of postmenopausal women were grouped into normal, osteopenic, and osteoporotic; dual-energy x-ray absorptiometry was the reference standard. RHSEG of the mandibular angle and canine/premolar trabecular regions of interest was performed.

Survival estimation through the cumulative hazard function with monotone natural cubic splines.

In this paper we explore the estimation of survival probabilities via a smoothed version of the survival function, in the presence of censoring. We investigate the fit of a natural cubic spline on the cumulative hazard function under appropriate constraints. Under the proposed technique the problem reduces to a restricted least squares one, leading to convex optimization.

Organizational attributes of practices successful at a disease management program.

Objective: To assess the contribution of organizational factors to implementation of 3 asthma quality measures: enrollment in a disease management program, development of a written treatment plan, and prescription of severity-appropriate anti-inflammatory therapy.

Study Design: A total of 138 pediatric clinicians and 247 office staff in 13 urban clinics and 23 nonurban private practices completed questionnaires about their practice's organizational characteristics (eg, leadership, communication, perceived effectiveness, job satisfaction).

Results: 94% of the clinicians and 92% of the office staff completed questionnaires.

Null mutation for macrophage migration inhibitory factor (MIF) is associated with less aggressive bladder cancer in mice.

Background: Inflammatory cytokines may promote tumorigenesis. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine with regulatory properties over tumor suppressor proteins involved in bladder cancer. We studied the development of bladder cancer in wild type (WT) and MIF knockout (KO) mice given N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN), a known carcinogen, to determine the role of MIF in bladder cancer initiation and progression.

Null mutation in macrophage migration inhibitory factor prevents muscle cell loss and fibrosis in partial bladder outlet obstruction.

Idiopathic detrusor underactivity (DU) and detrusor decompensation which develops following partial bladder outlet obstruction (pBOO) are both associated with smooth muscle degeneration and fibrosis. Macrophage migration inhibitory factor (MIF), an important mediator of bladder inflammation, has been shown to promote fibroblast survival and muscle death in other tissues. We evaluated the hypothesis that MIF has similar actions in the bladder by studying detrusor responses to pBOO or sham surgery in anesthetized female mice rendered null for the mif gene (MIF KO) and in wild-type (WT) controls, all killed 3 wk after surgery.

Racial and ethnic differences in diabetic patient-reported depression symptoms, diagnosis, and treatment.

Aims: Depression is common in diabetes, but little is known about depression in minorities with diabetes. This study investigated (1) racial/ethnic variation in depressive symptoms, (2) racial/ethnic variation in patient-reported physician-diagnosed depression, (3) racial/ethnic variation in patient-reported pharmacological depression treatment, and (4) the effects of demographic and diabetes variables on these outcomes.

Participants: A community sample of 740 persons with diabetes attending diabetes health fairs in the northeastern US participated.

Profile-likelihood inference for highly accurate diagnostic tests.

We consider profile-likelihood inference based on the multinomial distribution for assessing the accuracy of a diagnostic test. The methods apply to ordinal rating data when accuracy is assessed using the area under the receiver operating characteristic (ROC) curve. Simulation results suggest that the derived confidence intervals have acceptable coverage probabilities, even when sample sizes are small and the diagnostic tests have high accuracies.