Conditional ROC Curves for a Paired Case-Control Design

Many areas of research involve the analysis of correlated biomarker data. Correlated biomarker data arise from study designs including subjects that contain shared genetic or environmental factors. In a familial-matched design, the information about correlation might help to identify family members at increased risk of disease development and may lead to initiating treatment to slow or stop disease progression. Receiver operating characteristic (ROC) curves have been widely used in medical research to illustrate the performance of a biomarker in correctly distinguishing between diseased and non-diseased groups. Approaches appropriate to a familial-matched case-control design should accommodate inherent correlation in correctly estimating the biomarker’s ability to differentiate between groups, as well as handle estimation from a matched case-control design. It is sensible to expect biomarkers to demonstrate improved ability to partition between groups from a paired case-control design. There are not currently any known methods where the estimated performance based on ROC construction can reflect improved classification performance under a paired design. This dissertation will first review some developed methods for ROC curve estimation and will discuss the limitations and gaps of current methods for analyzing correlated familial paired data. A new approach using conditional ROC curves will be demonstrated to provide ROC curves for correlated paired data. The proposed approach will use the information about correlation among biomarker values, producing conditional ROC curves that evaluate the ability of a biomarker to discriminate between diseased and non-diseased subjects in a familial-paired design. Also, some extensions to this approach as well as an alternative approach to conditional ROC curve estimation for family paired case-control data are presented

A conditional approach for the receiver operating characteristic curve construction to evaluate diagnostic test performance in a family-matched case–control design

Receiver operating characteristic curves are widely used in medical research to illustrate biomarker performance in binary classification, particularly with respect to disease or health status. Study designs that include related subjects, such as siblings, usually have common environmental or genetic factors giving rise to correlated biomarker data. The design could be used to improve detection of biomarkers informative of increased risk, allowing initiation of treatment to stop or slow disease progression. Available methods for receiver operating characteristic construction do not take advantage of correlation inherent in this design to improve biomarker performance. This paper will briefly review some developed methods for receiver operating characteristic curve estimation in settings with correlated data from case–control designs and will discuss the limitations of current methods for analyzing correlated familial paired data. An alternative approach using conditional receiver operating characteristic curves will be demonstrated. The proposed approach will use information about correlation among biomarker values, producing conditional receiver operating characteristic curves that evaluate the ability of a biomarker to discriminate between affected and unaffected subjects in a familial paired design

Prediction of long-term survival among patients with cirrhosis using time-varying models

Risk prediction among patients with cirrhosis has historically focused on short-term (ie, 90 days) mortality among patients waitlisted for a transplant. Although several models have been developed to predict intermediate and longer term survivals, they have important limitations, namely, including only baseline laboratory and clinical variables to predict survival over a time horizon of years

Abstract P419: First-Trimester Maternal Hemodynamics In Patients With Or Without Chronic Hypertension Using USCOM (ultrasound Cardiac Output Monitor), A Non-invasive And Quantitative Method

Abstract only Objective: We aim to investigate maternal hemodynamics at 10-14 weeks of gestation among patients with and without chronic hypertension, utilizing USCOM®, a non-invasive cardiac output monitor. Methods: A prospective pilot study was conducted for women with singleton pregnancies. Independent T, Mann-Whitney U, and Chi-square tests were used to analyze cardiovascular parameters via Doppler waveform. Results: Thirteen pregnant women with preexisting hypertension and no other medical comorbidities were selected, and 26 controls were matched based on maternal age, ethnicity, and BMI in a ratio of 1:2. Six patients with chronic hypertension were on anti-hypertensive medications. Tables 1 and 2 present each respective group's basic demographic and hemodynamic characteristics. Conclusion: Despite no differences in BP, our study revealed significant hemodynamic changes in chronic hypertensive patients in the first trimester. Chronic hypertensive patients might have pre-existing pathological cardiovascular adaptation in early pregnancy, potentially compromising perinatal outcomes

Identification of miRNAs That Mediate Protective Functions of Anti-Cancer Drugs During White Matter Ischemic Injury

We have previously shown that two anti-cancer drugs, CX-4945 and MS-275, protect and preserve white matter (WM) architecture and improve functional recovery in a model of WM ischemic injury. While both compounds promote recovery, CX-4945 is a selective Casein kinase 2 (CK2) inhibitor and MS-275 is a selective Class I histone deacetylase (HDAC) inhibitor. Alterations in microRNAs (miRNAs) mediate some of the protective actions of these drugs. In this study, we aimed to (1) identify miRNAs expressed in mouse optic nerves (MONs); (2) determine which miRNAs are regulated by oxygen glucose deprivation (OGD); and (3) determine the effects of CX-4945 and MS-275 treatment on miRNA expression. RNA isolated from MONs from control and OGD-treated animals with and without CX-4945 or MS-275 treatment were quantified using NanoString nCounter ® miRNA expression profiling. Comparative analysis of experimental groups revealed that 12 miRNAs were expressed at high levels in MONs. OGD upregulated five miRNAs (miR-1959, miR-501-3p, miR-146b, miR-201, and miR-335-3p) and downregulated two miRNAs (miR-1937a and miR-1937b) compared to controls. OGD with CX-4945 upregulated miR-1937a and miR-1937b, and downregulated miR-501-3p, miR-200a, miR-1959, and miR-654-3p compared to OGD alone. OGD with MS-275 upregulated miR-2134, miR-2141, miR-2133, miR-34b-5p, miR-153, miR-487b, miR-376b, and downregulated miR-717, miR-190, miR-27a, miR-1959, miR-200a, miR-501-3p, and miR-200c compared to OGD alone. Interestingly, miR-501-3p and miR-1959 were the only miRNAs upregulated by OGD, and downregulated by OGD plus CX-4945 and MS-275. Therefore, we suggest that protective functions of CX-4945 or MS-275 against WM injury maybe mediated, in part, through miRNA expression