Medicine and Health Sciences Commons^™

Modeling The Incubation Period Of Anthrax, Ron Brookmeyer, Elizabeth Johnson, Sarah Barry

Ron Brookmeyer

Models of the incubation period of anthrax are important to public health planners because they can be used to predict the delay before outbreaks are detected, the size of an outbreak and the duration of time that persons should remain on antibiotics to prevent disease. The difficulty is that there is little direct data about the incubation period in humans. The objective of this paper is to develop and apply models for the incubation period of anthrax. Mechanistic models that account for the biology of spore clearance and germination are developed based on a competing risks formulation. The models predict …

Wavelet-Based Functional Mixed Models To Characterize Population Heterogeneity In Accelerometer Profiles: A Case Study. , Jeffrey S. Morris, Cassandra Arroyo, Brent A. Coull, Louise M. Ryan, Steven L. Gortmaker

Jeffrey S. Morris

We present a case study illustrating the challenges of analyzing accelerometer data taken from a sample of children participating in an intervention study designed to increase physical activity. An accelerometer is a small device worn on the hip that records the minute-by-minute activity levels of the child throughout the day for each day it is worn. The resulting data are irregular functions characterized by many peaks representing short bursts of intense activity. We model these data using the wavelet-based functional mixed model. This approach incorporates multiple fixed effects and random effect functions of arbitrary form, the estimates of which are …

Alternative Probeset Definitions For Combining Microarray Data Across Studies Using Different Versions Of Affymetrix Oligonucleotide Arrays, Jeffrey S. Morris, Chunlei Wu, Kevin R. Coombes, Keith A. Baggerly, Jing Wang, Li Zhang

Jeffrey S. Morris

Many published microarray studies have small to moderate sample sizes, and thus have low statistical power to detect significant relationships between gene expression levels and outcomes of interest. By pooling data across multiple studies, however, we can gain power, enabling us to detect new relationships. This type of pooling is complicated by the fact that gene expression measurements from different microarray platforms are not directly comparable. In this chapter, we discuss two methods for combining information across different versions of Affymetrix oligonucleotide arrays. Each involves a new approach for combining probes on the array into probesets. The first approach involves …

Identifying Important Explanatory Variables For Time-Varying Outcomes., Oliver Bembom, Maya L. Petersen, Mark J. Van Der Laan

Maya Petersen

This chapter describes a systematic and targeted approach for estimating the impact of each of a large number of baseline covariates on an outcome that is measured repeatedly over time. These variable importance estimates can be adjusted for a user-specified set of confounders and lend themselves in a straightforward way to obtaining confidence intervals and p-values. Hence, they can in particular be used to identify a subset of baseline covariates that are the most important explanatory variables for the time-varying outcome of interest. We illustrate the methodology in a data analysis aimed at finding mutations of the human immunodeficiency virus …

Identifying Important Explanatory Variables For Time-Varying Outcomes., Oliver Bembom, Maya L. Petersen, Mark J. Van Der Laan

Oliver Bembom

This chapter describes a systematic and targeted approach for estimating the impact of each of a large number of baseline covariates on an outcome that is measured repeatedly over time. These variable importance estimates can be adjusted for a user-specified set of confounders and lend themselves in a straightforward way to obtaining confidence intervals and p-values. Hence, they can in particular be used to identify a subset of baseline covariates that are the most important explanatory variables for the time-varying outcome of interest. We illustrate the methodology in a data analysis aimed at finding mutations of the human immunodeficiency virus …

Modeling An Outbreak Of Anthrax, Ron Brookmeyer

Ron Brookmeyer

Introduction

On October 2, 2001 a sixty-three-year-old Florida man who worked as a photo editor at a media publishing company was admitted to an emergency department complaining of nausea, vomiting, and fever. His symptoms began four days earlier on a recreational trip to North Carolina. The man died shortly thereafter. An astute clinician quickly made the surprising diagnosis of inhalational anthrax, which is a serious and deadly disease. The diagnosis was surprising because inhalational anthrax is extremely rare; only 18 cases were reported in the United States between 1900 and 1978. Public health officials at first believed that the Florida …

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.

Age-Related Dystrophin–Glycoprotein Complex Structure And Function In The Rat Extensor Digitorum Longus And Soleus Muscle, Kevin M. Rice, Deborah L. Preston, David Neff, Michael L. Norton, Eric R. Blough

Eric Blough

Age-Related Dystrophin–Glycoprotein Complex Structure And Function In The Rat Extensor Digitorum Longus And Soleus Muscle, Kevin M. Rice, Deborah L. Preston, David Neff, Michael L. Norton, Eric R. Blough

Kevin M Rice

Age-Related Dystrophin–Glycoprotein Complex Structure And Function In The Rat Extensor Digitorum Longus And Soleus Muscle, Kevin M. Rice, Deborah L. Preston, David Neff, Michael L. Norton, Eric R. Blough

Deborah L Preston

Neuroprotective And Disease-Modifying Effects Of The Ketogenic Diet, Maciej Gasior, Michael A. Rogawski, Adam L. Hartman

Michael A. Rogawski

The ketogenic diet has been in clinical use for over 80 years, primarily for the symptomatic treatment of epilepsy. A recent clinical study has raised the possibility that exposure to the ketogenic diet may confer long-lasting therapeutic benefits for patients with epilepsy. Moreover, there is evidence from uncontrolled clinical trials and studies in animal models that the ketogenic diet can provide symptomatic and disease-modifying activity in a broad range of neurodegenerative disorders including Alzheimer’s disease and Parkinson’s disease, and may also be protective in traumatic brain injury and stroke. These observations are supported by studies in animal models and isolated …

Some Statistical Issues In Microarray Gene Expression Data, Matthew S. Mayo, Byron J. Gajewski, Jeffrey S. Morris

Jeffrey S. Morris

In this paper we discuss some of the statistical issues that should be considered when conducting experiments involving microarray gene expression data. We discuss statistical issues related to preprocessing the data as well as the analysis of the data. Analysis of the data is discussed in three contexts: class comparison, class prediction and class discovery. We also review the methods used in two studies that are using microarray gene expression to assess the effect of exposure to radiofrequency (RF) fields on gene expression. Our intent is to provide a guide for radiation researchers when conducting studies involving microarray gene expression …

Diverse Mechanisms Of Antiepileptic Drugs In The Development Pipeline, Michael A. Rogawski

Michael A. Rogawski

There is a remarkable array of new chemical entities in the current antiepileptic drug (AED) development pipeline. In some cases, the compounds were synthesized in an attempt improve upon the activity of marketed AEDs. In other cases, the discovery of antiepileptic potential was largely serendipitous. Entry into the pipeline begins with the demonstration of activity in one or more animal screening models. Results from testing in a panel of such models provide a basis to differentiate agents and may offer clues as to the mechanism. Target activity may then be defined through cell-based studies, often years after the initial identification …

Probability Of Real -Time Detection Vs Probability Of Infection For Aerosolized Biowarfare Agents: A Model Study., Alexander G. Sabelnikov, Vladimir Zhukov, C Ruth Kempf

Alexander G Sabelnikov

No abstract provided.

Distinct Glycan Structures Of Uroplakins Ia And Ib, Bo Xie, Ge Zhou, Shiu-Yung Chan, Ellen Shapiro, Xiant-Peng Kong, Xue-Ru Wu, Tung-Tien Sun, Catherine E. Costello

Bo Xie

Although it has been shown that mouse uroplakin (UP) Ia, a major glycoprotein of urothelial apical surface, can serve as the receptor for the FimH lectin adhesin of type 1-fimbriated Escherichia coli, the organism that causes a great majority of urinary tract infections, the glycan structure of this native receptor was unknown. Using a sensitive approach that combines in-gel glycosidase and protease digestions, permethylation of released glycans, and mass spectrometry, we have elucidated for the first time the native glycoform structures of the mouse UPIa receptor and those of its non-binding homolog, UPIb, and have determined the glycosylation site occupancy. …

Activation In Neural Networks Controlling Ingestive Behaviors: What Does It Mean, And How Do We Map And Measure It?, Alan G. Watts, Arshad M. Khan, Graciela Sanchez-Watts, Dawna Salter, Christina M. Neuner

Arshad M. Khan, Ph.D.

No abstract provided.

Homeland Security: Engaging The Frontlines - Symposium Proceedings, George H. Baker, Cheryl J. Elliott

George H Baker

The rise of the American homeland security endeavor under the leadership of the new Department of Homeland Security has been heralded by several major national strategy documents. These documents have served to organize efforts at top levels within the government and industry. However, the national strategy guidance is not getting to many organizations and people at the grass-roots level who can make the most difference in preventing attacks, protecting systems, and recovering from catastrophic events, viz. the general citizenry, private infrastructure owners, and local governments. To better understand grass-roots issues and solutions, James Madison University, in cooperation with the Federal …

Biochemical Characterization Of The Major Sorghum Grain Peroxidase, Mamoudou H. Dicko, Harry Gruppen, Riet Hilhorst, Alphons G. J. Voragen, Willen W. H. Van Berkel

Pr. Mamoudou H. DICKO, PhD

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 …

Synchrony Of Change In Depressive Symptoms, Health Status, And Quality Of Life In Persons With Clinical Depression, Paula Diehr

Paula Diehr

BACKGROUND: Little is known about longitudinal associations among measures of depression, mental and physical health, and quality of life (QOL). We followed 982 clinically depressed persons to determine which measures changed and whether the change was synchronous with change in depressive symptoms. METHODS: Data were from the Longitudinal Investigation of Depression Outcomes (LIDO). Depressive symptoms, physical and mental health, and quality of life were measured at baseline, 6 weeks, 3 months, and 9 months. Change in the measures was examined over time and for persons with different levels of change in depressive symptoms. RESULTS: On average, all of the measures …

Shrinkage Estimation For Sage Data Using A Mixture Dirichlet Prior, Jeffrey S. Morris, Keith A. Baggerly, Kevin R. Coombes

Jeffrey S. Morris

Serial Analysis of Gene Expression (SAGE) is a technique for estimating the gene expression profile of a biological sample. Any efficient inference in SAGE must be based upon efficient estimates of these gene expression profiles, which consist of the estimated relative abundances for each mRNA species present in the sample. The data from SAGE experiments are counts for each observed mRNA species, and can be modeled using a multinomial distribution with two characteristics: skewness in the distribution of relative abundances and small sample size relative to the dimension. As a result of these characteristics, a given SAGE sample will fail …

An Introduction To High-Throughput Bioinformatics Data, Keith A. Baggerly, Kevin R. Coombes, Jeffrey S. Morris

Jeffrey S. Morris

High throughput biological assays supply thousands of measurements per sample, and the sheer amount of related data increases the need for better models to enhance inference. Such models, however, are more effective if they take into account the idiosyncracies associated with the specific methods of measurement: where the numbers come from. We illustrate this point by describing three different measurement platforms: microarrays, serial analysis of gene expression (SAGE), and proteomic mass spectrometry.

Bayesian Mixture Models For Gene Expression And Protein Profiles, Michele Guindani, Kim-Anh Do, Peter Mueller, Jeffrey S. Morris

Jeffrey S. Morris

We review the use of semi-parametric mixture models for Bayesian inference in high throughput genomic data. We discuss three specific approaches for microarray data, for protein mass spectrometry experiments, and for SAGE data. For the microarray data and the protein mass spectrometry we assume group comparison experiments, i.e., experiments that seek to identify genes and proteins that are differentially expressed across two biologic conditions of interest. For the SAGE data example we consider inference for a single biologic sample.

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 …

Identifying Placebo Effects With Data From Clinical Trials, Anup Malani

Anup Malani

A medical treatment is said to have placebo effects if patients who are optimistic about the treatment respond better to the treatment. This paper proposes a simple test for placebo effects. Instead of comparing the treatment and control arms of a single trial, one should compare the treatment arms of two trials with different probabilities of assignment to treatment. If there are placebo effects, patients in the higher-probability trial will experience better outcomes simply because they believe that there is a greater chance of receiving treatment. This paper finds evidence of placebo effects in trials of antiulcer and cholesterol-lowering drugs.

Tailor-Made Composite Functions As Tools In Model Choice: The Case Of Sigmoidal Vs. Bi-Linear Growth Profiles, Tobias I. Baskin, Winfried S. Peters

Tobias Baskin

Background Roots are the classical model system to study the organization and dynamics of organ growth zones. Profiles of the velocity of root elements relative to the apex have generally been considered to be sigmoidal. However, recent high-resolution measurements have yielded bi-linear profiles, suggesting that sigmoidal profiles may be artifacts caused by insufficient spatio-temporal resolution. The decision whether an empirical velocity profile follows a sigmoidal or bi-linear distribution has consequences for the interpretation of the underlying biological processes. However, distinguishing between sigmoidal and bi-linear curves is notoriously problematic. A mathematical function that can describe both types of curve equally well …

Cognitive-Vestibular Interactions: A Review Of Patient Difficulties And Possible Mechanisms, Douglas A. Hanes, Gin Mccollum

Gin McCollum

Cognitive deficits such as poor concentration and short-term memory loss are known by clinicians to occur frequently among patients with vestibular abnormalities. Although direct scientific study of such deficits has been limited, several types of investigations do lend weight to the existence of vestibular-cognitive effects. In this article we review a wide range of studies indicating a vestibular influence on the ability to perform certain cognitive functions. In addition to tests of vestibular patient abilities, these studies include dual-task studies of cognitive and balance functions, studies of vestibular contribution to spatial perception and memory, and works demonstrating a vestibular influence …

From Faculty For Undergraduate Neuroscience: Encouraging Innovation In Undergraduate Neuroscience Education By Supporting Student Research And Faculty Development, Eric Wiertelak, J. C. Hardwick, M. Kerchner, B. Lom, J. J. Ramirez

Eric Wiertelak

No abstract provided.

Reflections On… Phase Shifting Under Different Visual Conditions, Gavin Buckingham, David Carey, Arash Sahraie

Gavin Buckingham

When two limbs are moved out of time (i.e. opposing muscle activation at each limb) in rhythmic oscillatory movements, there is a tendency at high frequencies for the movements to synchronise in the temporal domain, resulting in bilateral homologous muscle activation known as a ‘phase shift’ (Kelso, 1984). In an effort to determine the degree with which perception influences this phase shifting behaviour (Mechsner et al., 2001), a mirror can be placed between the hands of participants, parallel to their mid-saggital plane such that the reflected hand appeared in the place of the occluded hand. This paradigm can be used …

Visual Adaptation To Masculine And Feminine Faces Influences Generalized Preferences And Perceptions Of Trustworthiness, Gavin Buckingham, L. Debruine, A. Little, L. Welling, C. Conway, B. Tiddeman, B. Jones

Gavin Buckingham

We compared the effects of adaptation to faces varying in sexual dimorphism of shape on perceptions of the trustworthiness and attractiveness of masculine faces.