Medical Biomathematics and Biometrics Commons^™

Dose Expansion Cohorts In Phase I Trials, Alexia Iasonos, John O'Quigley

Memorial Sloan-Kettering Cancer Center, Dept. of Epidemiology & Biostatistics Working Paper Series

A rapidly increasing number of Phase I dose-finding studies, and in particular those based on the standard 3+3 design, frequently prolong the study and include dose expansion cohorts (DEC) with the goal to better characterize the toxicity profiles of experimental agents and to study disease specific cohorts. These trials consist of two phases: the usual dose escalation phase that aims to establish the maximum tolerated dose (MTD) and the dose expansion phase that accrues additional patients, often with different eligibility criteria, and where additional information is being collected. Current protocols typically do not specify whether the MTD will be updated …

Dose Expansion Cohorts In Phase I Trials, Alexia Iasonos, John O'Quigley

Alexia Iasonos

A rapidly increasing number of Phase I dose-finding studies, and in particular those based on the standard 3+3 design, frequently prolong the study and include dose expansion cohorts (DEC) with the goal to better characterize the toxicity profiles of experimental agents and to study disease specific cohorts. These trials consist of two phases: the usual dose escalation phase that aims to establish the maximum tolerated dose (MTD) and the dose expansion phase that accrues additional patients, often with different eligibility criteria, and where additional information is being collected. Current protocols typically do not specify whether the MTD will be updated …

Health Care Information Technology: Securing The Electronic Health Record With Biometric Technology, Alyssa Iacona

The Review: A Journal of Undergraduate Student Research

The principal focus of this paper is to examine the integration of biometric technology into healthcare’s information technology systems. Biometric technology, a rapidly evolving mechanism, analyzes specific anatomical and physiological features of an individual for identity verification (Perrin, 2002). Moreover, as the federal government has mandated all health records to be electronic in 2014, the implementation of biometrics has become a prevalent means of security. In an effort to adhere to the patient privacy laws authorized by the Health Insurance Portability and Accountability Act (HIPAA), biometric recognition is currently used to restrict access to verified health care providers and detect …

Massively Parallel Nonparametric Regression, With An Application To Developmental Brain Mapping, Philip T. Reiss, Lei Huang, Yin-Hsiu Chen, Lan Huo, Thaddeus Tarpey, Maarten Mennes

Lei Huang

We propose a penalized spline approach to performing large numbers of parallel nonparametric analyses of either of two types: restricted likelihood ratio tests of a parametric regression model versus a general smooth alternative, and nonparametric regression. Compared with naively performing each analysis in turn, our techniques reduce computation time dramatically. Viewing the large collection of scatterplot smooths produced by our methods as functional data, we develop a clustering approach to summarize and visualize these results. Our approach is applicable to ultra-high-dimensional data, particularly data acquired by neuroimaging; we illustrate it with an analysis of developmental trajectories of functional connectivity at …

Tibial Tubercle Transfer To Correct Bilateral Patellar Tendinopathy In A Collegiate Football Player, Andrew D. Hamstra

Boise State University Theses and Dissertations

Objective: To present a case of a competitive football player with chronic patellar tendinopathy and the associated bilateral tibial tubercle transfer surgeries performed leading to the reduction of pain and return to participation.

Background: A 19 year-old male football athlete (height= 187.96 cm, mass= 112.037 kg) presented with chronic patellar tendinopathy that began in his high school career and continued to worsen with the increased physical demands associated with participation in collegiate sport.

Differential Diagnosis: Chondromalacia patella and Osgood Schlatters disease.

Treatment: After nonsurgical intervention resulted in no decrease of pain, bilateral tibial tubercle transfer surgery was conducted to correct …

Estimating The Impact Of Lost To Follow-Up On Breast Cancer Patients' Disease-Free Survival, Debbie Yan Qun Huang

Statistics

Background The 5-year survival rate for patients with breast cancer is much higher than patients with other types of cancer. Due to this longer survival period, breast cancer patients also tend to have increased rates of lost to follow-up, when compared to other cancers. When a patient becomes lost, the occurrence of distant metastasis cannot be reliably ascertained, unless the patient had a breast cancer-specific (BC) death. The impact of lost patients on recurrence rates and disease-free survival (DFS) was explored in breast cancer patients seen at the City of Hope from 1997 to 2012.

Methods Female breast cancer patients …

A Semantic-Based Method For Extracting Concept Definitions From Scientific Publications: Evaluation In The Autism Phenotype Domain, Saeed Hassanpour, Martin J. O’Connor, Amar K. Das

Dartmouth Scholarship

Background: A variety of informatics approaches have been developed that use information retrieval, NLP and text-mining techniques to identify biomedical concepts and relations within scientific publications or their sentences. These approaches have not typically addressed the challenge of extracting more complex knowledge such as biomedical definitions. In our efforts to facilitate knowledge acquisition of rule-based definitions of autism phenotypes, we have developed a novel semantic-based text-mining approach that can automatically identify such definitions within text.

Results: Using an existing knowledge base of 156 autism phenotype definitions and an annotated corpus of 26 source articles containing such definitions, we evaluated and …

Evaluation Of Student Outcomes In Online Vs. Campus Biostatistics Education In A Graduate School Of Public Health, John Mcgready, Ron Brookmeyer

Ron Brookmeyer

Objective: To compare student outcomes between concurrent online and on-campus sections of an introductory biostatistics course offered at a U.S. school of public health in 2005. Methods: Enrolled students (95 online, 92 on-campus) were invited to participate in a confidential online survey. The course outcomes were compared between the two sections adjusting for differences in student characteristics. Results: Seventy-two online (76%) and 66 (72%) on-campus enrollees participated. Unadjusted final exam scores for the online and on-campus sections were respectively 85.1 and 86.3 (p = 0.50) in term 1, and 87.7 and 86.9 (p=0.58) in term 2. After adjustment for student …

Global Quantitative Assessment Of The Colorectal Polyp Burden In Familial Adenomatous Polyposis Using A Web-Based Tool, Patrick M. Lynch, Jeffrey S. Morris, William A. Ross, Miguel A. Rodriguez-Bigas, Juan Posadas, Rossa Khalaf, Diane M. Weber, Valerie O. Sepeda, Bernard Levin, Imad Shureiqi

Jeffrey S. Morris

Background: Accurate measures of the total polyp burden in familial adenomatous polyposis (FAP) are lacking. Current assessment tools include polyp quantitation in limited-field photographs and qualitative total colorectal polyp burden by video.

Objective: To develop global quantitative tools of the FAP colorectal adenoma burden.

Design: A single-arm, phase II trial.

Patients: Twenty-seven patients with FAP.

Intervention: Treatment with celecoxib for 6 months, with before-treatment and after-treatment videos posted to an intranet with an interactive site for scoring.

Main Outcome Measurements: Global adenoma counts and sizes (grouped into categories: less than 2 mm, 2-4 mm, and greater than 4 mm) were …

Estimation Of Hiv Incidence Using Multiple Biomakers, Ron Brookmeyer, Jacob Konikoff, Oliver Laeyendecker, Susan Eshleman

Ron Brookmeyer

The incidence of human immunodeficiency virus (HIV) is the rate at which new HIV infections occur in populations. The development of accurate, practical, and cost-effective approaches to estimation of HIV incidence is a priority among researchers in HIV surveillance because of limitations with existing methods. In this paper, we develop methods for estimating HIV incidence rates using multiple biomarkers in biological samples collected from a cross-sectional survey. An advantage of the method is that it does not require longitudinal follow-up of individuals. We use assays for BED, avidity, viral load, and CD4 cell count data from clade B samples collected …

Sberia: Set Based Gene Environment Interaction Test For Rare And Common Variants In Complex Diseases, Shuo Jiao, Li Hsu, Stéphane Bézieau, Hermann Brenner, Andrew T. Chan, Jenny Chang-Claude, Loic Le Marchand, Mathieu Lemire, Polly A. Newcomb, Martha L. Slattery, Ulrike Peters

Shuo Jiao

Identification of gene-environment interaction (GxE) is important in understanding the etiology of complex diseases. However, partially due to the lack of power, there have been very few replicated GxE findings compared to the success in marginal association studies. The existing GxE testing methods mainly focus on improving the power for individual markers. In this paper, we took a different strategy and proposed a Set Based gene EnviRonment InterAction test (SBERIA), which can improve the power by reducing the multiple testing burdens and aggregating signals within a set. The major challenge of the signal aggregation within a set is how to …

Mixtures Of Receiver Operating Characteristic Curves, Mithat Gonen

Mithat Gönen

Rationale and Objectives: ROC curves are ubiquitous in the analysis of imaging metrics as markers of both diagnosis and prognosis. While empirical estimation of ROC curves remains the most popular method, there are several reasons to consider smooth estimates based on a parametric model.

Materials and Methods: A mixture model is considered for modeling the distribution of the marker in the diseased population motivated by the biological observation that here is more heterogeneity in the diseased population than there is in the normal one. It is shown that this model results in an analytically tractable ROC curve which is itself …

Varying-Smoother Models For Functional Responses, Philip T. Reiss, Lei Huang, Huaihou Chen, Stan Colcombe

Philip T. Reiss

This paper studies estimation of a smooth function f(x,v) when we are given functional responses of the form f(x, ·) + error, but scientific interest centers on the collection of functions f(·,v) for different v. The motivation comes from studies of human brain development, in which x denotes age whereas v refers to brain locations. Analogously to varying-coefficient models, in which the mean response is linear in x, the “varying-smoother” models that we consider exhibit nonlinear dependence on x that varies smoothly with v. We discuss three approaches to estimating varying-smoother models: (a) methods that employ a tensor product penalty; …

Piscine Myocarditis Virus (Pmcv) In Wild Atlantic Salmon Salmo Salar, Torstein Tengs Dr.

Dr. Torstein Tengs

Cardiomyopathy syndrome (CMS) is a severe cardiac disease of sea-farmed Atlantic salmon Salmo salar L., but CMS-like lesions have also been found in wild Atlantic salmon. In 2010 a double-stranded RNA virus of the Totiviridae family, provisionally named piscine myocarditis virus (PMCV), was described as the causative agent of CMS. In the present paper we report the first detection of PMCV in wild Atlantic salmon. The study is based on screening of 797 wild Atlantic salmon by real-time RT-PCR. The samples were collected from 35 different rivers along the coast of Norway, and all individuals included in the study were …

Paradoxical Results Of Adaptive False Discovery Rate Procedures In Neuroimaging Studies, Philip T. Reiss, Armin Schwartzman, Feihan Lu, Lei Huang, Erika Proal

Philip T. Reiss

Adaptive false discovery rate (FDR) procedures, which offer greater power than the original FDR procedure of Benjamini and Hochberg, are often applied to statistical maps of the brain. When a large proportion of the null hypotheses are false, as in the case of widespread effects such as cortical thinning throughout much of the brain, adaptive FDR methods can surprisingly reject more null hypotheses than not accounting for multiple testing at all—i.e., using uncorrected p-values. A straightforward mathematical argument is presented to explain why this can occur with the q-value method of Storey and colleagues, and a simulation study shows that …

A Pooled Analysis Of Smoking And Colorectal Cancer: Timing Of Exposure And Interactions With Environmental Factors

Shuo Jiao

Background:Considerable evidence suggests that cigarette smoking is associated with a higher risk of colorectal cancer. What is unclear, however, is the impact of quitting smoking on risk attenuation and whether other risk factors for colorectal cancer modify this association. Methods:We performed a pooled analysis of 8 studies, including 6,796 colorectal cancer cases and 7,770 controls to evaluate the association between cigarette smoking history and colorectal cancer risk, and to investigate potential effect modification by other risk factors. Results:Current smokers (OR=1.26, 95% CI=1.11-1.43) and former smokers (OR=1.18, 95% CI=1.09-1.27), relative to never smokers, showed higher risks of colorectal cancer. Former smokers …

Prevalence Of Tick Borne Encephalitis Virus In Tick Nymphs In Relation To Climatic Factors On The Southern Coast Of Norway, Torstein Tengs Dr.

Dr. Torstein Tengs

BACKGROUND

Tick-borne encephalitis (TBE) is among the most important vector borne diseases of humans in Europe and is currently identified as a major health problem in many countries. TBE endemic zones have expanded over the past two decades, as well as the number of reported cases within endemic areas. Multiple factors are ascribed for the increased incidence of TBE, including climatic change. The number of TBE cases has also increased in Norway over the past decade, and the human cases cluster along the southern coast of Norway. In Norway the distribution and prevalence of TBE virus (TBEV) in tick populations …

Function-On-Scalar Regression With The Refund Package, Philip T. Reiss

Philip T. Reiss

No abstract provided.

A Strain Of Piscine Myocarditis Virus (Pmcv) Infecting Argentina Silus (Ascanius), Torstein Tengs Dr.

Dr. Torstein Tengs

No abstract.

Comparing Years Of Healthy Life, Measured In 16 Ways, For Normal Weight And Overweight Older Adults, Paula Diehr

Paula Diehr

Introduction. The traditional definitions of overweight and obesity are not age specific, even though the relationship of weight to mortality is different for older adults. Effects of adiposity on aspects of health beside mortality have not been well investigated. Methods. We calculated the number of years of healthy life (YHL) in the 10 years after baseline, for 5,747 older adults. YHL was defined in 16 different ways. We compared Normal and Overweight persons, classified either by bodymass index (BMI) or by waist circumference (WC). Findings. YHL for Normal and Overweight persons differed significantly in 25% of the comparisons, of which …