Optimized Adaptive Enrichment Designs For Multi-Arm Trials: Learning Which Subpopulations Benefit From Different Treatments, 2017 Department of Biostatistics, Brown School of Public Health
Optimized Adaptive Enrichment Designs For Multi-Arm Trials: Learning Which Subpopulations Benefit From Different Treatments, Jon Arni Steingrimsson, Joshua Betz, Tiachen Qian, Michael Rosenblum
Johns Hopkins University, Dept. of Biostatistics Working Papers
We propose a class of adaptive randomized trial designs for comparing two treatments to a common control in two disjoint subpopulations. The type of adaptation, called adaptive enrichment, involves a preplanned rule for modifying enrollment and arm assignment based on accruing data in an ongoing trial. The motivation for this adaptive feature is that interim data may indicate that a subpopulation, such as those with lower disease severity at baseline, are unlikely to benefit from a particular treatment, while uncertainty remains for the other treatment and/or subpopulation. We developed a new multiple testing procedure tailored to this design problem ...
Constructing A Confidence Interval For The Fraction Who Benefit From Treatment, Using Randomized Trial Data, 2017 Johns Hopkins University School of Public Health, Department of Biostatistics
Constructing A Confidence Interval For The Fraction Who Benefit From Treatment, Using Randomized Trial Data, Emily J. Huang, Ethan X. Fang, Daniel F. Hanley, Michael Rosenblum
Johns Hopkins University, Dept. of Biostatistics Working Papers
The fraction who benefit from treatment is the proportion of patients whose potential outcome under treatment is better than that under control. Inference on this parameter is challenging since it is only partially identifiable, even in our context of a randomized trial. We propose a new method for constructing a confidence interval for the fraction, when the outcome is ordinal or binary. Our confidence interval procedure is pointwise consistent. It does not require any assumptions about the joint distribution of the potential outcomes, although it has the flexibility to incorporate various user-defined assumptions. Unlike existing confidence interval methods for partially ...
Impaired Fitness And Transmission Of Macrolide-Resistant Campylobacter Jejuni In Its Natural Host, 2017 Iowa State University
Impaired Fitness And Transmission Of Macrolide-Resistant Campylobacter Jejuni In Its Natural Host, Taradon Luangtongkum, Zhangqi Shen, Virginia W. Seng, Orhan Sahin, Byeonghwa Jeon, Peng Liu, Qijing Zhang
Campylobacter jejuni is a major zoonotic pathogen transmitted to humans via the food chain and is prevalent in chickens, a natural reservoir for this pathogenic organism. Due to the importance of macrolide antibiotics in clinical therapy of human campylobacteriosis, development of macrolide resistance in Campylobacter has become a concern for public health. To facilitate the control of macrolide-resistant Campylobacter, it is necessary to understand if macrolide resistance affects the fitness and transmission of Campylobacter in its natural host. In this study we conducted pairwise competitions and comingling experiments in chickens using clonally related and isogenic C. jejuni strains, which are ...
Mutational And Transcriptomic Changes Involved In The Development Of Macrolide Resistance In Campylobacter Jejuni, Haihong Hao, Zonghui Yuan, Zhangqi Shen, Jing Han, Orhan Sahin, Peng Liu, Qijing Zhang
Macrolide antibiotics are important for clinical treatment of infections caused by Campylobacter jejuni. Development of resistance to this class of antibiotics in Campylobacter is a complex process, and the dynamic molecular changes involved in this process remain poorly defined. Multiple lineages of macrolide-resistant mutants were selected by stepwise exposure of C. jejuni to escalating doses of erythromycin or tylosin. Mutations in target genes were determined by DNA sequencing, and the dynamic changes in the expression of antibiotic efflux transporters and the transcriptome of C. jejuni were examined by real-time reverse transcription-PCR, immunoblotting, and DNA microarray analysis. Multiple types of mutations ...
Multi-Omics Approaches To Deciphering A Hypervirulent Strain Of Campylobacter Jejuni, 2017 Iowa State University
Multi-Omics Approaches To Deciphering A Hypervirulent Strain Of Campylobacter Jejuni, Zuowei Wu, Orhan Sahin, Zhangqi Shen, Peng Liu, William G. Miller, Qijing Zhang
Campylobacter jejuni clone SA recently emerged as the predominant cause of sheep abortion in the United States and is also associated with foodborne gastroenteritis in humans. A distinct phenotype of this clone is its ability to induce bacteremia and abortion. To facilitate understanding the pathogenesis of this hypervirulent clone, we analyzed a clinical isolate (IA3902) of clone SA using multi-omics approaches. The genome of IA3902 contains a circular chromosome of 1,635,045 bp and a circular plasmid of 37,174 bp. Comparative genomic analysis revealed that IA3902 is most closely related to C. jejuni NCTC11168, which is a reference ...
Comparison Of Adaptive Randomized Trial Designs For Time-To-Event Outcomes That Expand Versus Restrict Enrollment Criteria, To Test Non-Inferiority, 2017 Johns Hopkins Bloomberg School of Public Health, Department of Biostatistics
Comparison Of Adaptive Randomized Trial Designs For Time-To-Event Outcomes That Expand Versus Restrict Enrollment Criteria, To Test Non-Inferiority, Josh Betz, Jon Arni Steingrimsson, Tianchen Qian, Michael Rosenblum
Johns Hopkins University, Dept. of Biostatistics Working Papers
Adaptive enrichment designs involve preplanned rules for modifying patient enrollment criteria based on data accrued in an ongoing trial. These designs may be useful when it is suspected that a subpopulation, e.g., defined by a biomarker or risk score measured at baseline, may benefit more from treatment than the complementary subpopulation. We compare two types of such designs, for the case of two subpopulations that partition the overall population. The first type starts by enrolling the subpopulation where it is suspected the new treatment is most likely to work, and then may expand inclusion criteria if there is early ...
Time Series Copulas For Heteroskedastic Data, 2017 Melbourne Business School
Time Series Copulas For Heteroskedastic Data, Ruben Loaiza-Maya, Michael S. Smith, Worapree Maneesoonthorn
Michael Stanley Smith
The Soybean Rhg1 Locus For Resistance To The Soybean Cyst Nematode Heterodera Glycines Regulates The Expression Of A Large Number Of Stress- And Defense-Related Genes In Degenerating Feeding Cells, 2017 University of Missouri
The Soybean Rhg1 Locus For Resistance To The Soybean Cyst Nematode Heterodera Glycines Regulates The Expression Of A Large Number Of Stress- And Defense-Related Genes In Degenerating Feeding Cells, Pramod Kaitheri Kandoth, Nagabhushana Ithal, Justin Recknor, Tom Maier, Dan Nettleton, Thomas J. Baum, Melissa G. Mitchum
To gain new insights into the mechanism of soybean (Glycine max) resistance to the soybean cyst nematode (Heterodera glycines), we compared gene expression profiles of developing syncytia in soybean near-isogenic lines differing at Rhg1 (for resistance to Heterodera glycines), a major quantitative trait locus for resistance, by coupling laser capture microdissection with microarray analysis. Gene expression profiling revealed that 1,447 genes were differentially expressed between the two lines. Of these, 241 (16.8%) were stress- and defense-related genes. Several stress-related genes were up-regulated in the resistant line, including those encoding homologs of enzymes that lead to increased levels of ...
Novel Bayesian Adaptive Clinical Trial Designs In Early Phases, 2017 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
Novel Bayesian Adaptive Clinical Trial Designs In Early Phases, Haitao Pan
UT GSBS Dissertations and Theses (Open Access)
Early phase, or phase I and phase II, trials are the first step in testing new medicines that have been developed in the lab. The main goal of phase I clinical trials is to establish the recommended dose of new drugs for phase II trials. For the cytotoxic drugs, the goal is to find maximum tolerated dose (MTD). The guiding principle for dose escalation in phase I trials is to avoid exposing too many patients to subtherapeutic doses while preserving safety and maintaining rapid accrual. Therefore, dose escalation methods, especially Bayesian designs, are recommended to be used in phase I ...
A Cross-Sectional Exploration Of Household Financial Reactions And Homebuyer Awareness Of Registered Sex Offenders In A Rural, Suburban, And Urban County., John Charles Navarro
Electronic Theses and Dissertations
As stigmatized persons, registered sex offenders betoken instability in communities. Depressed home sale values are associated with the presence of registered sex offenders even though the public is largely unaware of the presence of registered sex offenders. Using a spatial multilevel approach, the current study examines the role registered sex offenders influence sale values of homes sold in 2015 for three U.S. counties (rural, suburban, and urban) located in Illinois and Kentucky within the social disorganization framework. Homebuyers were surveyed to examine whether awareness of local registered sex offenders and the homebuyer’s community type operate as moderators between ...
Tree-Based Regression For Interval-Valued Data, 2017 Utah State University
Tree-Based Regression For Interval-Valued Data, Chih-Ching Yeh
All Graduate Plan B and other Reports
Regression methods for interval-valued data have been increasingly studied in recent years. As most of the existing works focus on linear models, it is important to note that many problems in practice are nonlinear in nature and therefore development of nonlinear regression tools for intervalvalued data is crucial. In this project, we propose a tree-based regression method for interval-valued data, which is well applicable to both linear and nonlinear problems. Unlike linear regression models that usually require additional constraints to ensure positivity of the predicted interval length, the proposed method estimates the regression function in a nonparametric way, so the ...
Methods For Scalar-On-Function Regression, 2017 Columbia University
Methods For Scalar-On-Function Regression, Philip T. Reiss, Jeff Goldsmith, Han Lin Shang, R. Todd Ogden
Philip T. Reiss
Marketing The Mountain State: A Large N Study Of User Engagement On Twitter, 2017 Illinois State University
Marketing The Mountain State: A Large N Study Of User Engagement On Twitter, Kirk Richardson
Capstone Projects – Politics and Government
Much of the evolving research on the use of social media in destination marketing emphasizes how information diffusion influences the reputational image of place. The present study uses Twitter data to focus on the relative differences in user engagement across discrete account types. Specifically, this is done to examine how the official destination marketing organization of Montana—the Montana Office of Tourism (MTOT)—performs relative to other account types. Several regression analyses conducted on Twitter data associated with an ongoing MTOT place branding campaign reveal that tweets sent from ‘official’ accounts are more likely to be retweeted, and are estimated ...
Qqs Orphan Gene Regulates Carbon And Nitrogen Partitioning Across Species Via Nf-Yc Interactions, 2017 Iowa State University
Qqs Orphan Gene Regulates Carbon And Nitrogen Partitioning Across Species Via Nf-Yc Interactions, Ling Li, Wenguang Zheng, Yanbing Zhu, Huaxun Ye, Buyun Tang, Zebulun W. Arendsee, Dallas Jones, Ruoran Li, Diego Ortiz, Xuefeng Zhao, Chuanlong Du, Dan Nettleton, M. Paul Scott, Maria G. Salas-Fernandez, Yanhai Yin, Eve S. Wurtele
M. Paul Scott
The allocation of carbon and nitrogen resources to the synthesis of plant proteins, carbohydrates, and lipids is complex and under the control of many genes; much remains to be understood about this process. QQS (Qua-Quine Starch; At3g30720), an orphan gene unique to Arabidopsis thaliana, regulates metabolic processes affecting carbon and nitrogen partitioning among proteins and carbohydrates, modulating leaf and seed composition in Arabidopsis and soybean. Here the universality of QQS function in modulating carbon and nitrogen allocation is exemplified by a series of transgenic experiments. We show that ectopic expression of QQS increases soybean protein independent of the genetic background ...
Moesin1 And Ve-Cadherin Are Required In Endothelial Cells During In Vivo Tubulogenesis, 2017 Iowa State University
Moesin1 And Ve-Cadherin Are Required In Endothelial Cells During In Vivo Tubulogenesis, Ying Wang, Mark S. Kaiser, Jon D. Larson, Aidas Nasevicius, Karl J. Clark, Shannon A. Wadman, Sharon E. Roberg-Perez, Stephen C. Ekker, Perry B. Hackett, Maura Mcgrail, Jeffrey J. Essner
Jeffrey J. Essner
Endothelial tubulogenesis is a crucial step in the formation of functional blood vessels during angiogenesis and vasculogenesis. Here, we use in vivo imaging of living zebrafish embryos expressing fluorescent fusion proteins of β-Actin, α-Catenin, and the ERM family member Moesin1 (Moesin a), to define a novel cord hollowing process that occurs during the initial stages of tubulogenesis in intersegmental vessels (ISVs) in the embryo. We show that the primary lumen elongates along cell junctions between at least two endothelial cells during embryonic angiogenesis. Moesin1-EGFP is enriched around structures that resemble intracellular vacuoles, which fuse with the luminal membrane during expansion ...
Trends In The Sand: Directional Evolution In The Shell Shape Of Recessing Scallops (Bivalvia: Pectinidae), 2017 Iowa State University
Trends In The Sand: Directional Evolution In The Shell Shape Of Recessing Scallops (Bivalvia: Pectinidae), Emma Sherratt, Alvin Alejandrino, Andrew C. Kraemer, Jeanne M. Serb, Dean C. Adams
Jeanne M Serb
Directional evolution is one of the most compelling evolutionary patterns observed in macroevolution. Yet, despite its importance, detecting such trends in multivariate data remains a challenge. In this study, we evaluate multivariate evolution of shell shape in 93 bivalved scallop species, combining geometric morphometrics and phylogenetic comparative methods. Phylomorphospace visualization described the history of morphological diversification in the group; revealing that taxa with a recessing life habit were the most distinctive in shell shape, and appeared to display a directional trend. To evaluate this hypothesis empirically, we extended existing methods by characterizing the mean directional evolution in phylomorphospace for recessing ...
Phenotypic Plasticity Of Native Vs. Invasive Purple Loosestrife: A Two-State Multivariate Approach, 2017 Iowa State University
Phenotypic Plasticity Of Native Vs. Invasive Purple Loosestrife: A Two-State Multivariate Approach, Young Jin Chun, Michael L. Collyer, Kirk A. Moloney, Jason D. Nason
Jason D Nason
The differences in phenotypic plasticity between invasive (North American) and native (German) provenances of the invasive plant Lythrum salicaria (purple loosestrife) were examined using a multivariate reaction norm approach testing two important attributes of reaction norms described by multivariate vectors of phenotypic change: the magnitude and direction of mean trait differences between environments. Data were collected for six life history traits from native and invasive plants using a split-plot design with experimentally manipulated water and nutrient levels. We found significant differences between native and invasive plants in multivariate phenotypic plasticity for comparisons between low and high water treatments within low ...
Propensity Score Analysis With Matching Weights, 2017 Cleveland Clinic
Propensity Score Analysis With Matching Weights, Liang Li
The propensity score analysis is one of the most widely used methods for studying the causal treatment effect in observational studies. This paper studies treatment effect estimation with the method of matching weights. This method resembles propensity score matching but offers a number of new features including efficient estimation, rigorous variance calculation, simple asymptotics, statistical tests of balance, clearly identified target population with optimal sampling property, and no need for choosing matching algorithm and caliper size. In addition, we propose the mirror histogram as a useful tool for graphically displaying balance. The method also shares some features of the inverse ...
Mechanistic Mathematical Models: An Underused Platform For Hpv Research, 2017 George Washington University
Mechanistic Mathematical Models: An Underused Platform For Hpv Research, Marc Ryser, Patti Gravitt, Evan R. Myers
Global Health Faculty Publications
Health economic modeling has become an invaluable methodology for the design and evaluation of clinical and public health interventions against the human papillomavirus (HPV) and associated diseases. At the same time, relatively little attention has been paid to a different yet complementary class of models, namely that of mechanistic mathematical models. The primary focus of mechanistic mathematical models is to better understand the intricate biologic mechanisms and dynamics of disease. Inspired by a long and successful history of mechanistic modeling in other biomedical fields, we highlight several areas of HPV research where mechanistic models have the potential to advance the ...
Swine Respiratory Disease Minimally Affects Responses Of Nursery Pigs To Gas Euthanasia, 2017 Iowa State University
Swine Respiratory Disease Minimally Affects Responses Of Nursery Pigs To Gas Euthanasia, Larry J. Sadler, Locke A. Karriker, Anna K. Butters-Johnson, Kent J. Schwartz, Tina M. Widowski, Chong Wang, Suzanne T. Millman
Anna K. Butters-Johnson
Objectives: To assess effects of swine respiratory disease (SRD) on nursery pig responses during gas euthanasia and to compare responses to carbon dioxide (CO2) and argon (Ar) gas euthanasia in terms of efficacy and welfare.
Materials and methods: Fifty-four pigs identified for euthanasia were classified as having SRD or euthanized for other reasons (OT). These pigs were distributed among three treatments: prefill CO2 (P-CO2), gradual fill CO2(G-CO2), and prefill Ar (P-Ar). Behavioral and physiological indicators of efficacy and welfare were assessed directly and from video. Modified atmosphere CO2 and O2concentrations (%) were collected throughout the process.
Results: Respiratory disease status ...