Physical Sciences and Mathematics Commons^™

Characterization Of Hiv Diversity, Phylodynamics And Drug Resistance In Washington, Dc., Marcos Pérez-Losada, Amanda D Castel, Brittany Lewis, Michael Kharfen, Charles P Cartwright, Bruce Huang, Taylor Maxwell, Alan E Greenberg, Keith A Crandall

Epidemiology Faculty Publications

No abstract provided.

Novel Models Of Visual Topographic Map Alignment In The Superior Colliculus., Ruben A Tikidji-Hamburyan, Tarek A El-Ghazawi, Jason W. Triplett

Pediatrics Faculty Publications

The establishment of precise neuronal connectivity during development is critical for sensing the external environment and informing appropriate behavioral responses. In the visual system, many connections are organized topographically, which preserves the spatial order of the visual scene. The superior colliculus (SC) is a midbrain nucleus that integrates visual inputs from the retina and primary visual cortex (V1) to regulate goal-directed eye movements. In the SC, topographically organized inputs from the retina and V1 must be aligned to facilitate integration. Previously, we showed that retinal input instructs the alignment of V1 inputs in the SC in a manner dependent on …

Phase I Dose-Escalation Trial Of Intravaginal Curcumin In Women For Cervical Dysplasia, Leda Gattoc, Paula M. Frew, Shontell N. Thomas, Kirk A. Easley, Laura Ward, H-H Sherry Chow, Chiemi A. Ura, Lisa Flowers

Environmental & Occupational Health Faculty Publications

Background: This is a Phase I trial demonstrating safety and tolerability of intravaginal curcumin for future use in women with cervical neoplasia. Objective: The objective of this study was to assess the safety, tolerability, and pharmacokinetics of intravaginal curcumin in healthy women. Study design: We conducted a 3+3 dose-escalation Phase I trial in a group of women aged 18–45 years. Thirteen subjects were given one of four doses of curcumin powder (500 mg, 1,000 mg, 1,500 mg, and 2,000 mg) packed in gelatin capsules, which was administered intravaginally daily for 14 days. The primary end point for this study was …

Improving Power In Group Sequential, Randomized Trials By Adjusting For Prognostic Baseline Variables And Short-Term Outcomes, Tianchen Qian, Michael Rosenblum, Huitong Qiu

Johns Hopkins University, Dept. of Biostatistics Working Papers

In group sequential designs, adjusting for baseline variables and short-term outcomes can lead to increased power and reduced sample size. We derive formulas for the precision gain from such variable adjustment using semiparametric estimators for the average treatment effect, and give new results on what conditions lead to substantial power gains and sample size reductions. The formulas reveal how the impact of prognostic variables on the precision gain is modified by the number of pipeline participants, analysis timing, enrollment rate, and treatment effect heterogeneity, when the semiparametric estimator uses correctly specified models. Given set prognostic value of baseline variables and …

Stochastic Optimization Of Adaptive Enrichment Designs For Two Subpopulations, Aaron Fisher, Michael Rosenblum

Johns Hopkins University, Dept. of Biostatistics Working Papers

An adaptive enrichment design is a randomized trial that allows enrollment criteria to be modified at interim analyses, based on a preset decision rule. When there is prior uncertainty regarding treatment effect heterogeneity, these trial designs can provide improved power for detecting treatment effects in subpopulations. We present a simulated annealing approach to search over the space of decision rules and other parameters for an adaptive enrichment design. The goal is to minimize the expected number enrolled or expected duration, while preserving the appropriate power and Type I error rate. We also explore the benefits of parallel computation in the …

An Examination Of The Neural Unreliability Thesis Of Autism, John Butler, Sophie Molholm, Gizely Andrade, John J. Foxe

Articles

An emerging neuropathological theory of Autism, referred to here as “the neural unreliability thesis,” proposes greater variability in moment-to-moment cortical representation of environmental events, such that the system shows general instability in its impulse response function. Leading evidence for this thesis derives from functional neuroimaging, a methodology ill-suited for detailed assessment of sensory transmission dynamics occurring at the millisecond scale. Electrophysiological assessments of this thesis, however, are sparse and unconvincing. We conducted detailed examination of visual and somatosensory evoked activity using high-density electrical mapping in individuals with autism (N = 20) and precisely matched neurotypical controls (N = 20), recording …

Student Lifestyle Choices And Perceptions Of Stress Based On Majors, Nathan Robinson, Seth Andrews, Benjamin E. Yoder

Exercise Science Senior Research Projects

College students are often experience many stressors. This study was designed to look at perceived-stress and health habits with relation to academic department of undergraduate students at Cedarville University. The results of this study have implications for the Physical Activity and the Christian Life (PACL) class, offered on the Cedarville campus, in assessing its current curriculum and making potential future adjustments to the course. The objective of this study was to answer the question: “Do perceived stress levels within different academic departments affect health habits in Cedarville University undergraduate students?”

The study was conducted with a campus-wide, 27 question survey …

Very Rapid Onset Cannabis Dependence Risk In Relation To Co-Occurring Use Of Other Psychoactive Drugs, Olga A. Vsevolozhskaya, Fernando A. Wagner, James C. Anthony

Biostatistics Presentations

Background: Epidemiological estimates for lifetime cumulative incidence indicate that for every 9-11 who start using cannabis, one becomes a case of the cannabis dependence syndrome (CDS) – i.e., roughly 9%-11%. More recent estimates clarify that CDS risk might be much lower among ’cannabis only’ users, due in part to the fact that many ’cannabis only’ users try the drug a few times and never again. We turned to Hill functional analysis in order to study CDS probability soon after 1st cannabis use, estimated across strata defined by the number of recent days of cannabis use, with an acknowledgment that a …

Self-Reported Sleep Apnea And Dementia Risk: Findings From The Prevention Of Alzheimer's Disease With Vitamin E And Selenium Trial, Xiuhua Ding, Richard J. Kryscio, Joshua Turner, Gregory A. Jicha, Gregory E. Cooper, Allison M. Caban-Holt, Frederick A. Schmitt, Erin L. Abner

Sanders-Brown Center on Aging Faculty Publications

OBJECTIVES: To investigate the association between baseline sleep apnea and risk of incident dementia in the Prevention of Alzheimer's Disease with Vitamin E and Selenium (PREADViSE) study and to explore whether the association depends on apolipoprotein E (APOE) ɛ4 allele status.

DESIGN: Secondary analysis based on data collected during PREADViSE.

SETTING: Participants were assessed at 128 local clinical study sites during the clinical trial phase and later were followed by telephone from a centralized location.

PARTICIPANTS: Men enrolled in PREADViSE (without dementia or other active neurological conditions that affect cognition such as major psychiatric disorders, including depression; N = …

The Decay Of Disease Association With Declining Linkage Disequilibrium: A Fine Mapping Theorem, Mehdi Maadooliat, Naveen K. Bansal, Jibal Upadhya, Manzur R. Farazi, Xiang Li, Max M. He, Scott J. Hebbring, Zhan Ye, Steven J. Schrodi

Mathematics, Statistics and Computer Science Faculty Research and Publications

Several important and fundamental aspects of disease genetics models have yet to be described. One such property is the relationship of disease association statistics at a marker site closely linked to a disease causing site. A complete description of this two-locus system is of particular importance to experimental efforts to fine map association signals for complex diseases. Here, we present a simple relationship between disease association statistics and the decline of linkage disequilibrium from a causal site. Specifically, the ratio of Chi-square disease association statistics at a marker site and causal site is equivalent to the standard measure of pairwise …

Pertussis-Associated Pneumonia In Infants And Children From Low- And Middle-Income Countries Participating In The Perch Study., Breanna Barger-Kamate, Maria Deloria Knoll, E Wangeci Kagucia, Christine Prosperi, Henry C Baggett, Daniel E. Park, +31 Additional Authors

Epidemiology Faculty Publications

BACKGROUND:  Few data exist describing pertussis epidemiology among infants and children in low- and middle-income countries to guide preventive strategies.

METHODS:  Children 1-59 months of age hospitalized with World Health Organization-defined severe or very severe pneumonia in 7 African and Asian countries and similarly aged community controls were enrolled in the Pneumonia Etiology Research for Child Health study. They underwent a standardized clinical evaluation and provided nasopharyngeal and oropharyngeal swabs and induced sputum (cases only) for Bordetella pertussis polymerase chain reaction. Risk factors and pertussis-associated clinical findings were identified.

RESULTS:  Bordetella pertussis was detected in 53 of 4200 (1.3%) cases …

Analysis Of Hiv Diversity In Hiv-Infected Black Men Who Have Sex With Men (Hptn 061), Iris Chen, Gordon Chau, Jing Wang, William Clarke, Mark A. Marzinke, Manya Magnus, +14 Additional Authors

Epidemiology Faculty Publications

Background

HIV populations often diversify in response to selective pressures, such as the immune response and antiretroviral drug use. We analyzed HIV diversity in Black men who have sex with men who were enrolled in the HIV Prevention Trials Network 061 study.

Methods

A high resolution melting (HRM) diversity assay was used to measure diversity in six regions of the HIV genome: two in gag, one in pol, and three in env. HIV diversity was analyzed for 146 men who were HIV infected at study enrollment, including three with acute infection and 13 with recent infection (identified …

Birth Mass Is The Key To Understanding The Negative Correlation Between Lifespan And Body Size In Dogs, Rong Fan, Gayla R. Olbricht, Xavior Baker, Chen Hou

Mathematics and Statistics Faculty Research & Creative Works

Larger dog breeds live shorter than the smaller ones, opposite of the mass-lifespan relationship observed across mammalian species. Here we use data from 90 dog breeds and a theoretical model based on the first principles of energy conservation and life history tradeoffs to explain the negative correlation between longevity and body size in dogs. We found that the birth/adult mass ratio of dogs scales negatively with adult size, which is different than the weak interspecific scaling in mammals. Using the model, we show that this ratio, as an index of energy required for growth, is the key to understanding why …

Asymptotic Behavior Of Even-Order Damped Differential Equations With P-Laplacian Like Operators And Deviating Arguments, Qingmin Liu, Martin Bohner, Said R. Grace, Tongxing Li

Mathematics and Statistics Faculty Research & Creative Works

We study the asymptotic properties of the solutions of a class of even-order damped differential equations with p-Laplacian like operators, delayed and advanced arguments. We present new theorems that improve and complement related contributions reported in the literature. Several examples are provided to illustrate the practicability, maneuverability, and efficiency of the results obtained. An open problem is proposed.

An Efficient And Long-Time Accurate Third-Order Algorithm For The Stokes–Darcy System, Wenbin Chen, Max Gunzburger, Dong Sun, Xiaoming Wang

Mathematics and Statistics Faculty Research & Creative Works

A third order in time numerical IMEX-type algorithm for the Stokes–Darcy system for flows in fluid saturated karst aquifers is proposed and analyzed. a novel third-order Adams–Moulton scheme is used for the discretization of the dissipative term whereas a third-order explicit Adams–Bashforth scheme is used for the time discretization of the interface term that couples the Stokes and Darcy components. the scheme is efficient in the sense that one needs to solve, at each time step, decoupled Stokes and Darcy problems. Therefore, legacy Stokes and Darcy solvers can be applied in parallel. the scheme is also unconditionally stable and, with …

Projective-Planar Graphs With No K3,4-Minor. Ii., John Maharry, Dan Slilaty

Mathematics and Statistics Faculty Publications

The authors previously published an iterative process to generate a class of projectiveplanar K3,4-free graphs called ‘patch graphs’. They also showed that any simple, almost 4-connected, nonplanar, and projective-planar graph that is K3,4-free is a subgraph of a patch graph. In this paper, we describe a simpler and more natural class of cubic K3,4- free projective-planar graphs which we call M¨obius hyperladders. Furthermore, every simple, almost 4-connected, nonplanar, and projective-planar graph that is K3,4-free is a minor of a M¨obius hyperladder. As applications of these structures we determine the page number of patch graphs and of M¨obius hyperladders.

Impact Of Myh6 Variants In Hypoplastic Left Heart Syndrome, Aoy Tomita-Mitchell, Karl D. Stamm, Donna K. Mahnke, Min-Su Kim, Pip M. Hidestrand, Huan-Ling Liang, Mary Goetsch, Pippa Simpson, Andrew N. Pelech, James S. Tweddell, D. Woodrow Benson, John Lough, Michael E. Mitchell

Mathematics, Statistics and Computer Science Faculty Research and Publications

Hypoplastic left heart syndrome (HLHS) is a clinically and anatomically severe form of congenital heart disease (CHD). Although prior studies suggest that HLHS has a complex genetic inheritance, its etiology remains largely unknown. The goal of this study was to characterize a risk gene in HLHS and its effect on HLHS etiology and outcome. We performed next-generation sequencing on a multigenerational family with a high prevalence of CHD/HLHS, identifying a rare variant in the α-myosin heavy chain (MYH6) gene. A case-control study of 190 unrelated HLHS subjects was then performed and compared with the 1000 Genomes Project. Damaging …

Managing The Spread Of Alfalfa Stem Nematodes (Ditylenchus Dipsaci): The Relationship Between Crop Rotation Periods And Pest Re-Emergence, S. Jordan, Claudia Nischwitz, R. Ramirez, Luis F. Gordillo

Mathematics and Statistics Faculty Publications

Alfalfa is a critical cash/rotation crop in the western region of the United States, where it is common to find crops affected by the alfalfa stem nematode (Ditylenchus dipsaci). Understanding the spread dynamics associated with this pest would allow growers to design better management programs and farming practices. This understanding is of particular importance given that there are no nematicides available against alfalfa stem nematodes and control strategies largely rely on crop rotation to non-host crops or by planting resistant varieties of alfalfa. In this paper we present a basic host-parasite model that describes the spread of the …

Inter-Relationships Linking Probability Of Becoming A Case Of Nicotine Dependence With Frequency Of Tobacco Cigarette Smoking, Olga A. Vsevolozhskaya, James C. Anthony

Biostatistics Faculty Publications

INTRODUCTION: Once smoking starts, some tobacco cigarette smokers (TCS) can make very rapid transitions into tobacco dependence syndromes (TCD). With adjustment for smoking frequency, we posit female excess risk for this rapid-onset TCD. In a novel application of functional analysis for tobacco research, we estimate four Hill function parameters and plot TCD risk against a gradient of smoking frequency, as observed quite soon after smoking onset.

METHODS: In aggregate, the National Surveys of Drug Use and Health, 2004-2013, identified 1546 newly incident TCS in cross-sectional research, each with standardized TCD assessment.

RESULTS: Hill function estimates contradict our apparently over-simplistic hypothesis. …

Regional Mapping Of Flow And Wall Characteristics Of Intracranial Aneurysms, Juan R. Cebral, Xinjie Duan, Piyusha S. Gade, Bong Jae Chung, Fernando Mut, Khaled Aziz, Anne M. Robertson

Department of Applied Mathematics and Statistics Faculty Scholarship and Creative Works

The evolution of intracranial aneurysms (IAs) is thought to be driven by progressive wall degradation in response to abnormal hemodynamics. Previous studies focused on the relationship between global hemodynamics and wall properties. However, hemodynamics, wall structure and mechanical properties of cerebral aneurysms can be non-uniform across the aneurysm wall. Therefore, the aim of this work is to introduce a methodology for mapping local hemodynamics to local wall structure in resected aneurysm specimens. This methodology combines image-based computational fluid dynamics, tissue resection, micro-CT imaging of resected specimens mounted on 3D-printed aneurysm models, alignment to 3D vascular models, multi-photon microscopy of the …

A Note On The Howson Property In Inverse Semigroups, Peter Jones

Mathematics, Statistics and Computer Science Faculty Research and Publications

An algebra has the Howson property if the intersection of any two finitely generated subalgebras is again finitely generated. A simple necessary and sufficient condition is given for the Howson property to hold on an inverse semigroup with finitely many idempotents. In addition, it is shown that any monogenic inverse semigroup has the Howson property.

Integration Over Curves And Surfaces Defined By The Closest Point Mapping, Catherine Kublik, Richard Tsai

Mathematics Faculty Publications

We propose a new formulation for integrating over smooth curves and surfaces that are described by their closest point mappings. Our method is designed for curves and surfaces that are not defined by any explicit parameterization and is intended to be used in combination with level set techniques. However, contrary to the common practice with level set methods, the volume integrals derived from our formulation coincide exactly with the surface or line integrals that one wishes to compute. We study various aspects of this formulation and provide a geometric interpretation of this formulation in terms of the singular values of …

Impact Of Myh6 Variants In Hypoplastic Left Heart Syndrome, Aoy Tomita-Mitchell, Karl D. Stamm, Donna K. Mahnke, Min-Su Kim, Pip M. Hidestrand, Huan-Ling Liang, Mary A. Goetsch, Mats Hidestrand, Pippa Simpson, Andrew N. Pelech, James S. Tweddell, D. Woodrow Benson, John Lough, Michael Mitchell

Mathematics, Statistics and Computer Science Faculty Research and Publications

Hypoplastic left heart syndrome (HLHS) is a clinically and anatomically severe form of congenital heart disease (CHD). Although prior studies suggest that HLHS has a complex genetic inheritance, its etiology remains largely unknown. The goal of this study was to characterize a risk gene in HLHS and its effect on HLHS etiology and outcome. We performed next-generation sequencing on a multigenerational family with a high prevalence of CHD/HLHS, identifying a rare variant in the α-myosin heavy chain (MYH6) gene. A case-control study of 190 unrelated HLHS subjects was then performed and compared with the 1000 Genomes Project. Damaging …

Genomics And Csf Analyses Implicate Thyroid Hormone In Hippocampal Sclerosis Of Aging, Peter T. Nelson, Yuriko Katsumata, Kwangsik Nho, Sergey C. Artiushin, Gregory A. Jicha, Wang-Xia Wang, Erin L. Abner, Andrew J. Saykin, Walter A. Kukull, Alzheimer’S Disease Neuroimaging Initiative (Adni), David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

We report evidence of a novel pathogenetic mechanism in which thyroid hormone dysregulation contributes to dementia in elderly persons. Two single nucleotide polymorphisms (SNPs) on chromosome 12p12 were the initial foci of our study: rs704180 and rs73069071. These SNPs were identified by separate research groups as risk alleles for non-Alzheimer’s neurodegeneration. We found that the rs73069071 risk genotype was associated with hippocampal sclerosis (HS) pathology among people with the rs704180 risk genotype (National Alzheimer’s Coordinating Center/Alzheimer’s Disease Genetic Consortium data; n = 2113, including 241 autopsy-confirmed HS cases). Furthermore, both rs704180 and rs73069071 risk genotypes were associated with widespread brain …

Efficiency Of Two Sample Tests Via The T-Mean Survival Time For Analyzing Event Time Observations, Lu Tian, Haoda Fu, Stephen J. Ruberg, Hajime Uno, Lj Wei

Harvard University Biostatistics Working Paper Series

In comparing two treatments with the event time observations, the hazard ratio (HR) estimate is routinely used to quantify the treatment difference. However, this model dependent estimate may be difficult to interpret clinically especially when the proportional hazards (PH) assumption is violated. An alternative estimation procedure for treatment efficacy based on the restricted means survival time or t-year mean survival time (t-MST) has been discussed extensively in the statistical and clinical literature. On the other hand, a statistical test 1 via the HR or its asymptotically equivalent counterpart, the logrank test, is asymptotically distribution-free. In this paper, we assess the …

Effects Of Cell Cycle Noise On Excitable Gene Circuits, Alan Veliz-Cuba, Chinmaya Gupta, Matthew R. Bennett, Krešimir Josić, William Ott

Mathematics Faculty Publications

We assess the impact of cell cycle noise on gene circuit dynamics. For bistable genetic switches and excitable circuits, we find that transitions between metastable states most likely occur just after cell division and that this concentration effect intensifies in the presence of transcriptional delay. We explain this concentration effect with a three-states stochastic model. For genetic oscillators, we quantify the temporal correlations between daughter cells induced by cell division. Temporal correlations must be captured properly in order to accurately quantify noise sources within gene networks.

Convolutions And Green’S Functions For Two Families Of Boundary Value Problems For Fractional Differential Equations, Paul W. Eloe, Jeffrey T. Neugebauer

Mathematics Faculty Publications

We consider families of two-point boundary value problems for fractional differential equations where the fractional derivative is assumed to be the Riemann-Liouville fractional derivative. The problems considered are such that appropriate differential operators commute and the problems can be constructed as nested boundary value problems for lower order fractional differential equations. Green's functions are then constructed as convolutions of lower order Green's functions. Comparison theorems are known for the Green's functions for the lower order problems and so, we obtain analogous comparison theorems for the two families of higher order equations considered here. We also pose a related open question …

Using Sensitivity Analyses For Unobserved Confounding To Address Covariate Measurement Error In Propensity Score Methods, Kara E. Rudolph, Elizabeth A. Stuart

Johns Hopkins University, Dept. of Biostatistics Working Papers

Propensity score methods are a popular tool to control for confounding in observational data, but their bias-reduction properties are threatened by covariate measurement error. There are few easy-to-implement methods to correct for such bias. We describe and demonstrate how existing sensitivity analyses for unobserved confounding---propensity score calibration, Vanderweele and Arah's bias formulas, and Rosenbaum's sensitivity analysis---can be adapted to address this problem. In a simulation study, we examined the extent to which these sensitivity analyses can correct for several measurement error structures: classical, systematic differential, and heteroscedastic covariate measurement error. We then apply these approaches to address covariate measurement error …

Inflammatory Properties Of Diet And Glucose-Insulin Homeostasis In A Cohort Of Iranian Adults, Nazanin Moslehi, Behnaz Ehsani, Parvin Mirmiran, Nitin Shivappa, Maryam Tohidi, James R. Hébert, Fereidoun Azizi

Faculty Publications

We aimed to investigate associations of the dietary inflammatory index (DII) with glucose-insulin homeostasis markers, and the risk of glucose intolerance. This cross-sectional study included 2975 adults from the Tehran Lipid and Glucose Study. Fasting plasma glucose (FPG), 2-h post-load glucose (2h-PG), and fasting serum insulin were measured. Homeostatic model assessment of insulin resistance index (HOMA-IR) and β-cell function (HOMA-B), and the quantitative insulin sensitivity check index (QUICKI) were calculated. Glucose tolerance abnormalities included impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes (T2DM). DII scores were positively associated with 2h-PG (β = 0.04; p = 0.05). …

Confidence Intervals For Heritability Via Haseman-Elston Regression, Tamar Sofer

UW Biostatistics Working Paper Series

Heritability is the proportion of phenotypic variance in a population that is attributable to individual genotypes. Heritability is considered an important measure in both evolutionary biology and in medicine, and is routinely estimated and reported in genetic epidemiology studies. In population-based genome-wide association studies (GWAS), mixed models are used to estimate variance components, from which a heritability estimate is obtained. The estimated heritability is the proportion of the model's total variance that is due to the genetic relatedness matrix (kinship measured from genotypes). Current practice is to use bootstrapping, which is slow, or normal asymptotic approximation to estimate the precision …