Biostatistics Commons^™

The Association Between Lifestyle Factors And Inflammatory Markers, Kerry Ann Stonebrook

Loma Linda University Electronic Theses, Dissertations & Projects

Background: Cardiovascular disease (CVD) is the leading cause of death for both men and women in the United States. While smoking, high blood pressure, and elevated cholesterol levels are established risk factors for CVD, inflammation is being evaluated as a potential independent risk factor. A key cytokine regulator of the inflammatory response, interleukin-1 (IL-1), has emerged as playing a particularly important role at the genetic level in determining the degree to which the inflammation pathway is turned on. How an individual’s genetic make-up affects inflammation, CVD risk, and response to lifestyle intervention is an area of research that is in …

Supervised Detection Of Conserved Motifs In Dna Sequences With Cosmo, Oliver Bembom, Sunduz Keles, Mark J. Van Der Laan

Oliver Bembom

A number of computational methods have been proposed for identifying transcription factor binding sites from a set of unaligned sequences that are thought to share the motif in question. We here introduce an algorithm, called cosmo, that allows this search to be supervised by specifying a set of constraints that the position weight matrix of the unknown motif must satisfy. Such constraints may be formulated, for example, on the basis of prior knowledge about the structure of the transcription factor in question. The algorithm is based on the same two-component multinomial mixture model used by MEME, with stronger reliance, however, …

The Causal Effect Of Recent Leisure-Time Physical Activity On All-Cause Mortality Among The Elderly, Oliver Bembom, Mark J. Van Der Laan, Ira B. Tager

Oliver Bembom

We analyze data collected as part of a prospective cohort study of elderly people living in and around Sonoma, CA, in order to estimate, for each round of interviews, the causal effect of leisure-time physical activity (LTPA) over the past year on the risk of mortality in the following two years. For each round of interviews, this effect is estimated separately for subpopulations defined based on past exercise habits, age, and whether subjects have had cardiac events in the past. This decomposition of the original longitudinal data structure into a series of point-treatment data structures corresponds to an application of …

Analysis Of Multi-Level Correlated Data In The Framework Of Generalized Estimating Equations Via Xtmultcorr Procedures In Stata And Qls Functions In Matlab, Justine Shults, Sarah J. Ratcliffe

UPenn Biostatistics Working Papers

No abstract provided.

A Satscan Macro Accessory For Cartography (Smac) Package Implemented With Sas Software, Allyson M. Abrams, Ken P. Kleinman

Public Health Department Faculty Publication Series

BACKGROUND:

SaTScan is a software program written to implement the scan statistic; it can be used to find clusters in space and/or time. It must often be run multiple times per day when doing disease surveillance. Running SaTScan frequently via its graphical user interface can be cumbersome, and the output can be difficult to visualize.

RESULTS:

The SaTScan Macro Accessory for Cartography (SMAC) package consists of four SAS macros and was designed as an easier way to run SaTScan multiple times and add graphical output. The package contains individual macros which allow the user to make the necessary input files …

Pre-Processing Mass Spectrometry Data, Kevin R. Coombes, Keith A. Baggerly, Jeffrey S. Morris

Jeffrey S. Morris

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 …

Unconditional Efficient One-Sided Confidence Limits For The Odds Ratio Based On Conditional Likelihood, Chris Lloyd, Max Moldovan

Chris J. Lloyd

We compare various one-sided confidence limits for the odds ratio in a 2x2 table. The first group of limits relies on first order asymptotic approximations and includes limits based on the (signed) likelihood ratio, score and Wald statistics. The second group of limits is based on the conditional tilted hypergeometric distribution, with and without mid-P correction. All these limits have poor unconditional coverage properties and so we apply the general transformation of Buehler (1957) to obtain limits which are unconditionally exact. The performance of these competing exact limits is assessed across a range of sample sizes and parameter values by …

Efficient And Exact Tests Of The Risk Ratio In A Correlated 2x2 Table With Structural Zero, Chris Lloyd

Chris J. Lloyd

For a correlated 2x2 table where the (01) cell is empty by design, the parameter of interest is typically the ratio of the probability of secondary response conditional on primary response to the probability of primary response, also known as a risk ratio. It is common to test whether or not the risk ratio equals one. One method of obtaining an exact P-value is to maximise the tail probability of the test statistic over the nuisance parameter. It is argued that better results are obtained by first replacing the nuisance parameter by its profile estimate in the calculation of its …

Site Variation In Ems Treatment, Transport And Survival In Relation To Restoration Of Spontaneous Circulation (Rosc) For Adult Out-Of-Hospital Cardiac Arrest: The Resuscitation Outcomes Consortium (Roc) Epistry, Mohamud R. Daya, Kent M. Koprowicz, Dana M. Zive, Julie E. Cummins, Gena K. Sears, Terri A. Schmidt, Shannon W. Stephens, Ian G. Stiell

Kent M Koprowicz

Introduction: EMS protocols outlining when to attempt and terminate resuscitation for non-traumatic out-of- hospital cardiac arrest (OHCA) vary substantially across North America. The ROC Epistry is a prospective population based cohort study with uniform Utstein-style data definitions from 11 sites in North America. The purpose of this study was to compare site variation in EMS treatment and transport percentages within the ROC Epistry. We also examined the differences in overall survival in relation to the presence of ROSC prior to transport. Methods: Analysis of ROC Epistry data from 7 sites for all patients > 20 years of age with OHCA between …

Is A Basketball Free-Throw Sequence Nonrandom? A Group Exercise For Undergraduate Statistics Students, Stephen C. Adolph

All HMC Faculty Publications and Research

I describe a group exercise that I give to my undergraduate biostatistics class. The exercise involves analyzing a series of 200 consecutive basketball free-throw attempts to determine whether there is any evidence for sequential dependence in the probability of making a free-throw. The students are given the exercise before they have learned the appropriate statistical tests, so that they can come up with ideas on their own. Students spend a full class period working on the problem, with my guidance and hints. In the next class period, we discuss how each student group approached the problem. I then present several …

An Adaptive Dose Finding Design (Dosefind) Using A Nonlinear Dose Response Model, James Michael Davenport

Theses and Dissertations

First-in-man (FIM) Phase I clinical trials are part of the critical path in the development of a new compound entity (NCE). Since FIM clinical trials are the first time that an NCE is dosed in human subjects, the designs used in these trials are unique and geared toward patient safety. We develop a method for obtaining the desired response using an adaptive non-linear approach. This method is applicable for studies in which MTD, NOEL,NOAEL, PK, PD effects or other such endpoints are evaluated to determine the desired dose. The method has application whenever a measurable PD marker is an indicator …

Phase Ii Trials Powered To Detect Activity In Tumor Subsets With Retrospective (Or Prospective) Use Of Predictive Markers, Grishma S. Sheth

Theses and Dissertations

Classical phase II trial designs assume a patient population with a homogeneous tumor type and yield an estimate of a stochastic probability of tumor response. Clinically, however, oncology is moving towards identifying patients who are likely to respond to therapy using tumor subtyping based upon predictive markers. Such designs are called targeted designs (Simon, 2004). For a given phase I1 trial predictive markers may be defined prospectively (on the basis of previous results) or identified retrospectively on the basis of analysis of responding and non-responding tumors. For the prospective case we propose two Phase I1 targeted designs in which a) …

Chess, Chance And Conspiracy, Mark Segal

Mark R Segal

Chess and chance are seemingly strange bedfellows. Luck and/or randomness have no apparent role in move selection when the game is played at the highest levels. However, when competition is at the ultimate level, that of the World Chess Championship (WCC), chess and conspiracy are not strange bedfellows, there being a long and colorful history of accusations levied between participants. One such accusation, frequently repeated, was that all the games in the 1985 WCC (Karpov vs Kasparov) were fixed and prearranged move by move. That this claim was advanced by a former World Champion, Bobby Fischer, argues that it ought …

Software To Forecast The Global Burden Of Alzheimer's Disease, Ron Brookmeyer, Elizabeth Johnson, Kathryn Ziegler-Graham, H. Michael Arrighi

Ron Brookmeyer

Software was developed to forecast the global burden of Alzheimer’s disease and evaluate the potential impact of interventions that delay disease onset and progression. The output includes 50 year projections of Alzheimer's disease prevalence by stage of disease and region of the world. The methods are based on a stochastic multi-state model The software incorporates U.N. worldwide population forecasts and data from epidemiological studies on risks of Alzheimer’s disease. The user can also supply their own population projections, and modify input parameters for the model including the disease incidence rates, effects of interventions on disease onset and progression, and stages …

Confidence Intervals For Biomarker-Based Human Immunodeficiecny Virus Incidence Estimates And Differences Using Prevalent Data, Ron Brookmeyer, S Cole, H Chu

Ron Brookmeyer

Prevalent biological specimens can be used to estimate human immunodeficiency virus (HIV) incidence using a two-stage immunologic testing algorithm that hinges on the average time, say T, between testing HIV positive on highly and less sensitive enzyme immunoassays. Common approaches to confidence interval (CI) estimation for this incidence measure have included (1) ignoring the random error in T or (2) employing a Bonferroni adjustment to the box method. The authors present alternative Monte Carlo-based CIs for this incidence measure, as well as CIs for the biomarker-based incidence difference; standard approaches to CIs are typically appropriate for the incidence ratio. Using …

Modeling The Effect Of Alzheimer's Disease On Mortality, Elizabeth Johnson, Ron Brookmeyer, Kathryn Ziegler-Graham

Ron Brookmeyer

Mortality rate ratios and the associated proportional hazards models have been used to summarize the effect of Alzheimer's disease on longevity. However, the mortality rate ratios vary by age and therefore do not provide a simple parsimonious summary of the effect of the disease on lifespan. Instead, we propose a new parameter that is defined by an additive multistate model. The proposed multistate model accounts for different stages of disease progression. The underlying assumption of the model is that the effect of disease on mortality is to add a constant amount to death rates once the disease progresses from an …

A Practical Illustration Of The Importance Of Realistic Individualized Treatment Rules In Causal Inference, Oliver Bembom, Mark J. Van Der Laan

Oliver Bembom

The effect of vigorous physical activity on mortality in the elderly is difficult to estimate using conventional approaches to causal inference that define this effect by comparing the mortality risks corresponding to hypothetical scenarios in which all subjects in the target population engage in a given level of vigorous physical activity. A causal effect defined on the basis of such a static treatment intervention can only be identified from observed data if all subjects in the target population have a positive probability of selecting each of the candidate treatment options, an assumption that is highly unrealistic in this case since …