Applied Mathematics Commons^™

Comment On Global Dynamics Of Biological Systems, Radhakrishnan Nagarajan

Radhakrishnan Nagarajan

No abstract provided.

Models Of Phototransduction In Rod Photoreceptors, Harihar Khanal, Vasilios Alexiades

Publications

Phototransduction is the process by which photons of light generate an electrical response in retinal rod and cone photoreceptors, thereby initiating vision. We compare the electrical response in salamander rods from increasingly more (spacialy) detailed models of phototransduction: 0-dimensional (bulk), 1-dimensional (longitudinal), 2-dimensional (axisymmetric), and 3-dimensional (with incisures). We discuss issues of finding physical parameters for simulation and validation of models, and also present some computational experiments for rods with geometry of mouse and human photoreceptors.

Cascading Infrastructure Failures: Avoidance And Response, George H. Baker, Cheryl J. Elliott

George H Baker

No critical infrastructure is self-sufficient. The complexity inherent in the interdependent nature of infrastructure systems complicates planning and preparedness for system failures. Recent wide-scale disruption of infrastructure on the Gulf Coast due to weather, and in the Northeast due to electric power network failures, dramatically illustrate the problems associated with mitigating cascading effects and responding to cascading infrastructure failures once they have occurred.

The major challenge associated with preparedness for cascading failures is that they transcend system, corporate, and political boundaries and necessitate coordination among multiple, disparate experts and authorities. This symposium brought together concerned communities including government and industry …

Statistical Issues In Proteomic Research, Jeffrey S. Morris

Jeffrey S. Morris

No abstract provided.

Global Stability Results Of An Sis Age-Structured Epidemic Model With Vertical Transmission, M. El-Doma

Applications and Applied Mathematics: An International Journal (AAM)

An SIS age-structured epidemic model for a vertically as well as horizontally transmitted disease is investigated when the fertility, mortality and cure rates depend on age and the force of infection of proportionate mixing assumption type. We determine the steady states and prove the global stability for the endemic equilibriums.

A Large-Scale Rheumatoid Arthritis Genetic Study Identifies Association At Chr 9q33.2, Steven J. Schrodi

Steven J Schrodi

No abstract provided.

Laser Capture Sampling And Analytical Issues In Proteomics, Howard Gutstein, Jeffrey S. Morris

Jeffrey S. Morris

Proteomics holds the promise of evaluating global changes in protein expression and post-translational modificaiton in response to environmental stimuli. However, difficulties in achieving cellular anatomic resolution and extracting specific types of proteins from cells have limited the efficacy of these techniques. Laser capture microdissection has provided a solution to the problem of anatomical resolution in tissues. New extraction methodologies have expanded the range of proteins identified in subsequent analyses. This review will examine the application of laser capture microdissection to proteomic tissue sampling, and subsequent extraction of these samples for differential expression analysis. Statistical and other quantitative issues important for …

An Epidemiological Model Of Rift Valley Fever, Holly D. Gaff, David M. Hartley, Nicole P. Leahy

Biological Sciences Faculty Publications

We present and explore a novel mathematical model of the epidemiology of Rift Valley Fever (RVF). RVF is an Old World, mosquito-borne disease affecting both livestock and humans. The model is an ordinary differential equation model for two populations of mosquito species, those that can transmit vertically and those that cannot, and for one livestock population. We analyze the model to find the stability of the disease-free equlibrium and test which model parameters affect this stability most significantly. This model is the basis for future research into the predication of future outbreaks in the Old World and the assessment of …

Multiphoton Response Of Retinal Rod Photoreceptors, Vasilios Alexiades, Harihar Khanal

Publications

Phototransduction is the process by which light is converted into an electrical response in retinal photoreceptors. Rod photoreceptors contain a stack of (about 1000) disc membranes packed with photopigment rhodopsin molecules, which absorb the photons. We present computational experiments which show the profound effect on the response of the distances (how many discs apart) photons happen to be absorbed at. This photon-distribution effect alone can account for much of the observed variability in response.

Stability Analysis For An Seir Age-Structured Epidemic Model Under Vaccination, M. El-Doma

Applications and Applied Mathematics: An International Journal (AAM)

An SEIR age-structured epidemic model is investigated when susceptible and immune individuals are vaccinated indiscriminately and the force of infection of proportionate mixing type. We determine the steady states and obtain an explicitly computable threshold condition, and then study the stability of the steady states.

Global Stability Results And Well Posedness Of An Si Age-Structured Epidemic Model With Vertical Transmission, M. El-Doma

Applications and Applied Mathematics: An International Journal (AAM)

An SI age-structured epidemic model for a vertically as well as horizontally transmitted disease is investigated when the fertility and mortality rates depend on age and the force of infection of proportionate mixing assumption type. We prove the well posedness of the model as well as the global stability for endemic equilibriums.

Spatio-Temporal Analysis Of Areal Data And Discovery Of Neighborhood Relationships In Conditionally Autoregressive Models, Subharup Guha, Louise Ryan

Harvard University Biostatistics Working Paper Series

No abstract provided.

Prepms: Tof Ms Data Graphical Preprocessing Tool, Yuliya V. Karpievitch, Elizabeth G. Hill, Adam J. Smolka, Jeffrey S. Morris, Kevin R. Coombes, Keith A. Baggerly, Jonas S. Almeida

Jeffrey S. Morris

We introduce a simple-to-use graphical tool that enables researchers to easily prepare time-of-flight mass spectrometry data for analysis. For ease of use, the graphical executable provides default parameter settings experimentally determined to work well in most situations. These values can be changed by the user if desired. PrepMS is a stand-alone application made freely available (open source), and is under the General Public License (GPL). Its graphical user interface, default parameter settings, and display plots allow PrepMS to be used effectively for data preprocessing, peak detection, and visual data quality assessment.

A Stochastic Model For Psa Levels: Behavior Of Solutions And Population Statistics, Pavel Bělík, P W A Dayananda, John T. Kemper, Mikhail M. Shvartsman

Faculty Authored Articles

This paper investigates the partial differential equation for the evolving distribution of prostate-specific antigen (PSA) levels following radiotherapy. We also present results on the behavior of moments for the evolving distribution of PSA levels and estimate the probability of long-term treatment success and failure related to values of treatment and disease parameters. Results apply to a much wider range of parameter values than was considered in earlier studies, including parameter combinations that are patient specific.

Analysis Of An Sirs Age-Structured Epidemic Model With Vaccination And Vertical Transmission Of Disease, Mohammed El-Doma

Applications and Applied Mathematics: An International Journal (AAM)

An SIRS age-structured epidemic model for a vertically as well as horizontally transmitted disease under vaccination is investigated when the fertility, mortality and removal rates depend on age and the force of infection of proportionate mixing assumption type, and vaccination wanes over time. We prove the existence and uniqueness of solution to the model equations, and show that solutions of the model equations depend continuously on the initial age-distributions. Furthermore, we determine the steady states and obtain an explicitly computable threshold condition, in terms of the demographic and epidemiological parameters of the model; we then study the stability of the …

Wavelet-Based Functional Mixed Models, Jeffrey S. Morris, Raymond J. Carroll

Jeffrey S. Morris

Increasingly, Increasingly, scientific studies yield functional data, in which the ideal units of observation are curves and the observed data consist of sets of curves that are sampled on a fine grid. We present new methodology that generalizes the linear mixed model to the functional mixed model framework, with model fitting done by using a Bayesian wavelet-based approach. This method is flexible, allowing functions of arbitrary formand the full range of fixed effects structures and between-curve covariance structures that are available in the mixed model framework. It yields nonparametric estimates of the fixed and random-effects functions as well as the …

Analysis Of Mass Spectrometry Data Using Bayesian Wavelet-Based Functional Mixed Models, Jeffrey S. Morris, Philip J. Brown, Keith A. Baggerly, Kevin R. Coombes

Jeffrey S. Morris

In this chapter, we demonstrate how to analyze MALDI-TOF/SELDITOF mass spectrometry data using the wavelet-based functional mixed model introduced by Morris and Carroll (2006), which generalizes the linear mixed models to the case of functional data. This approach models each spectrum as a function, and is very general, accommodating a broad class of experimental designs and allowing one to model nonparametric functional effects for various factors, which can be conditions of interest (e.g. cancer/normal) or experimental factors (blocking factors). Inference on these functional effects allows us to identify protein peaks related to various outcomes of interest, including dichotomous outcomes, categorical …

Optimal Therapy Regimens For Treatment-Resistant Mutations Of Hiv, Weiqing Gu, Helen Moore

All HMC Faculty Publications and Research

In this paper, we use control theory to determine optimal treatment regimens for HIV patients, taking into account treatment-resistant mutations of the virus. We perform optimal control analysis on a model developed previously for the dynamics of HIV with strains of various resistance to treatment (Moore and Gu, 2005). This model incorporates three types of resistance to treatments: strains that are not responsive to protease inhibitors, strains not responsive to reverse transcriptase inhibitors, and strains not responsive to either of these treatments. We solve for the optimal treatment regimens analytically and numerically. We find parameter regimes for which optimal dosing …

Gauss-Seidel Estimation Of Generalized Linear Mixed Models With Application To Poisson Modeling Of Spatially Varying Disease Rates, Subharup Guha, Louise Ryan

Harvard University Biostatistics Working Paper Series

Generalized linear mixed models (GLMMs) provide an elegant framework for the analysis of correlated data. Due to the non-closed form of the likelihood, GLMMs are often fit by computational procedures like penalized quasi-likelihood (PQL). Special cases of these models are generalized linear models (GLMs), which are often fit using algorithms like iterative weighted least squares (IWLS). High computational costs and memory space constraints often make it difficult to apply these iterative procedures to data sets with very large number of cases.

This paper proposes a computationally efficient strategy based on the Gauss-Seidel algorithm that iteratively fits sub-models of the GLMM …

Computational Techniques For Spatial Logistic Regression With Large Datasets, Christopher J. Paciorek, Louise Ryan

Harvard University Biostatistics Working Paper Series

In epidemiological work, outcomes are frequently non-normal, sample sizes may be large, and effects are often small. To relate health outcomes to geographic risk factors, fast and powerful methods for fitting spatial models, particularly for non-normal data, are required. We focus on binary outcomes, with the risk surface a smooth function of space. We compare penalized likelihood models, including the penalized quasi-likelihood (PQL) approach, and Bayesian models based on fit, speed, and ease of implementation.

A Bayesian model using a spectral basis representation of the spatial surface provides the best tradeoff of sensitivity and specificity in simulations, detecting real spatial …

A Mathematical Model For Treatment-Resistant Mutations Of Hiv, Helen Moore, Weiqing Gu

All HMC Faculty Publications and Research

In this paper, we propose and analyze a mathematical model, in the form of a system of ordinary differential equations, governing mutated strains of human immunodeficiency virus (HIV) and their interactions with the immune system and treatments. Our model incorporates two types of resistant mutations: strains that are not responsive to protease inhibitors, and strains that are not responsive to reverse transcriptase inhibitors. It also includes strains that do not have either of these two types of resistance (wild-type virus) and strains that have both types. We perform our analysis by changing the system of ordinary differential equations (ODEs) to …

A Hybrid Newton-Type Method For The Linear Regression In Case-Cohort Studies, Menggang Yu, Bin Nan

The University of Michigan Department of Biostatistics Working Paper Series

Case-cohort designs are increasingly commonly used in large epidemiological cohort studies. Nan, Yu, and Kalbeisch (2004) provided the asymptotic results for censored linear regression models in case-cohort studies. In this article, we consider computational aspects of their proposed rank based estimating methods. We show that the rank based discontinuous estimating functions for case-cohort studies are monotone, a property established for cohort data in the literature, when generalized Gehan type of weights are used. Though the estimating problem can be formulated to a linear programming problem as that for cohort data, due to its easily uncontrollable large scale even for a …

Data Adaptive Estimation Of The Treatment Specific Mean, Yue Wang, Oliver Bembom, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

An important problem in epidemiology and medical research is the estimation of the causal effect of a treatment action at a single point in time on the mean of an outcome, possibly within strata of the target population defined by a subset of the baseline covariates. Current approaches to this problem are based on marginal structural models, i.e., parametric models for the marginal distribution of counterfactural outcomes as a function of treatment and effect modifiers. The various estimators developed in this context furthermore each depend on a high-dimensional nuisance parameter whose estimation currently also relies on parametric models. Since misspecification …

History-Adjusted Marginal Structural Models And Statically-Optimal Dynamic Treatment Regimes, Mark J. Van Der Laan, Maya L. Petersen

U.C. Berkeley Division of Biostatistics Working Paper Series

Marginal structural models (MSM) provide a powerful tool for estimating the causal effect of a treatment. These models, introduced by Robins, model the marginal distributions of treatment-specific counterfactual outcomes, possibly conditional on a subset of the baseline covariates. Marginal structural models are particularly useful in the context of longitudinal data structures, in which each subject's treatment and covariate history are measured over time, and an outcome is recorded at a final time point. However, the utility of these models for some applications has been limited by their inability to incorporate modification of the causal effect of treatment by time-varying covariates. …

Studying Effects Of Primary Care Physicians And Patients On The Trade-Off Between Charges For Primary Care And Specialty Care Using A Hierarchical Multivariate Two-Part Model, John W. Robinson, Scott L. Zeger, Christopher B. Forrest

Johns Hopkins University, Dept. of Biostatistics Working Papers

Objective. To examine effects of primary care physicians (PCPs) and patients on the association between charges for primary care and specialty care in a point-of-service (POS) health plan.

Data Source. Claims from 1996 for 3,308 adult male POS plan members, each of whom was assigned to one of the 50 family practitioner-PCPs with the largest POS plan member-loads.

Study Design. A hierarchical multivariate two-part model was fitted using a Gibbs sampler to estimate PCPs' effects on patients' annual charges for two types of services, primary care and specialty care, the associations among PCPs' effects, and within-patient associations between charges for …

A Hierarchical Multivariate Two-Part Model For Profiling Providers' Effects On Healthcare Charges, John W. Robinson, Scott L. Zeger, Christopher B. Forrest

Johns Hopkins University, Dept. of Biostatistics Working Papers

Procedures for analyzing and comparing healthcare providers' effects on health services delivery and outcomes have been referred to as provider profiling. In a typical profiling procedure, patient-level responses are measured for clusters of patients treated by providers that in turn, can be regarded as statistically exchangeable. Thus, a hierarchical model naturally represents the structure of the data. When provider effects on multiple responses are profiled, a multivariate model rather than a series of univariate models, can capture associations among responses at both the provider and patient levels. When responses are in the form of charges for healthcare services and sampled …

Non-Parametric Estimation Of Roc Curves In The Absence Of A Gold Standard, Xiao-Hua Zhou, Pete Castelluccio, Chuan Zhou

UW Biostatistics Working Paper Series

In evaluation of diagnostic accuracy of tests, a gold standard on the disease status is required. However, in many complex diseases, it is impossible or unethical to obtain such the gold standard. If an imperfect standard is used as if it were a gold standard, the estimated accuracy of the tests would be biased. This type of bias is called imperfect gold standard bias. In this paper we develop a maximum likelihood (ML) method for estimating ROC curves and their areas of ordinal-scale tests in the absence of a gold standard. Our simulation study shows the proposed estimates for the …

Incorporating Death Into Health-Related Variables In Longitudinal Studies, Paula Diehr, Laura Lee Johnson, Donald L. Patrick, Bruce Psaty

UW Biostatistics Working Paper Series

Background: The aging process can be described as the change in health-related variables over time. Unfortunately, simple graphs of available data may be misleading if some people die, since they may confuse patterns of mortality with patterns of change in health. Methods have been proposed to incorporate death into self-rated health (excellent to poor) and the SF-36 profile scores, but not for other variables.

Objectives: (1) To incorporate death into the following variables: ADLs, IADLs, mini-mental state examination, depressive symptoms, body mass index (BMI), blocks walked per week, bed days, hospitalization, systolic blood pressure, and the timed walk. (2) To …

Estimation Of Standardized Mortality Ratio In Geographic Epidemiology, Anna Kettermann

Electronic Theses and Dissertations

The analysis of geographic variation of disease and its representation on a map form an important topic of research in epidemiology and in public health in general. Identification of spatial heterogeneity of relative risk using morbidity and mortality data is required. The usual technique of disease atlas generation consists of data collection (observed number of disease cases). These data are collected during a continuous period of time (5 to 10 years). The second aspect of atlas creation relates to the analysis of these data. A traditional measure of the spatial variation is usually taken as a ratio of the number …

Response Of Dark-Adapted Retinal Rod Photoreceptors, H. Khanal, V. Alexiades, E. Dibenedetto

Publications

The process of phototransduction, whereby light is converted into an electrical response, in rod and cone photoreceptors in the retina, involves as a key setp, the diffusion of the cytoplasmic, signaling molecules cGMP (cyclic guanosime monophosphate) and Ca²+ diffuse in the cytoplasm (the fluid surrounding the discs). the complex geometry of the rod creates computational difficulties. We present spatio-temporal compuational models for interacctions and diffusion of cGMP and Ca²+ in the cytoplasm of vertebrate rod photoreceptors, as well as numerical simulations fo the response to light of dark-adapted Salamander rods.