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Medical Biomathematics and Biometrics Commons™
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- Discipline
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- Causal Inference (7)
- Causal inference (4)
- Aging (3)
- Cardiovascular Health Study (CHS) (3)
- Evggfp exc/vgood/good/fair/poor/(dead) self-rated health (3)
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- Health Status and Years of Healthy Life (3)
- Proteomics (3)
- Transition Probabilities and Multistate Life Tables (3)
- Aging and Older Adults (2)
- Counterfactual (2)
- Double robust estimation (2)
- Exact confidence intervals (2)
- Experimental Design (2)
- False Discovery Rate (2)
- G-computation estimation (2)
- Inverse probability of treatment-weighted estimation (2)
- Mass Spectrometry (2)
- Mortality (2)
- Randomization (2)
- Sequentially randomized trial (2)
- 2-DE (1)
- 2D Gels (1)
- Alzheimer's (1)
- Applied Research (1)
- B-splines (1)
- Berger-Boos (1)
- Computational Biology (1)
- Conditional inference (1)
- Cross-validation (1)
- DNA (1)
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Articles 1 - 23 of 23
Full-Text Articles in Medical Biomathematics and Biometrics
Statistical Issues In Proteomic Research, Jeffrey S. Morris
Statistical Issues In Proteomic Research, Jeffrey S. Morris
Jeffrey S. Morris
No abstract provided.
Exact One-Sided Confidence Limits For The Difference Between Two Correlated Proportions, Chris Lloyd, Max V. Moldovan
Exact One-Sided Confidence Limits For The Difference Between Two Correlated Proportions, Chris Lloyd, Max V. Moldovan
Chris J. Lloyd
We construct exact and optimal one-sided upper and lower confidence bounds for the difference between two probabilities based on matched binary pairs using well-established optimality theory of Buehler (1957). Starting with five different approximate loer and upper limits, we adjust them to have coverage probability exactly equal to the desired nominal level and then compare the resulting exact limits by their mean size. Exact limits based on the signed root likelihood ratio statistic are preferred and recommended for practical use.
Weight, Mortality, Years Of Healthy Life, And Active Life Expectancy In Older Adults, Paula Diehr
Weight, Mortality, Years Of Healthy Life, And Active Life Expectancy In Older Adults, Paula Diehr
Paula Diehr
OBJECTIVES: To determine whether weight categories predict subsequent mortality and morbidity in older adults. DESIGN: Multistate life tables, using data from the Cardiovascular Health Study, a longitudinal population-based cohort of older adults. SETTING: Data were provided by community-dwelling seniors in four U.S. counties: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Allegheny County, Pennsylvania. PARTICIPANTS: Five thousand eight hundred eighty-eight adults aged 65 and older at baseline. MEASUREMENTS: The age- and sex-specific probabilities of transition from one health state to another and from one weight category to another were estimated. From these probabilities, future life expectancy, years …
The Number Of Sick Persons In A Cohort, Paula Diehr
The Number Of Sick Persons In A Cohort, Paula Diehr
Paula Diehr
To see if the number of sick persons in a cohort was approximately constant over time, we calculated the number of sick persons in a “research” cohort of older adults followed for up to 14 years, and also in a synthetic birth cohort. Methods: In the research cohort, we calculated the actual number of persons in each health state over time, using eight different definitions of “sick”. For the birth cohort, we estimated the number of sick persons each year after birth. Results: The number of sick persons in the research cohort was approximately constant for 14 years, for all …
Statistical Methods For Analyzing Sequentially Randomized Trials, Oliver Bembom, Mark J. Van Der Laan
Statistical Methods For Analyzing Sequentially Randomized Trials, Oliver Bembom, Mark J. Van Der Laan
Oliver Bembom
In this issue of JNCI, Thall et al. present the results of a clinical trial that makes use of sequential randomization, a novel trial design that allows the investigator to study adaptive treatment strategies. Our aim is to complement this groundbreaking work by reviewing the current state of the art of statistical methods available for such analyses. Using the data collected by Thall et al. as an example, we focus on two different approaches for estimating the success rates of different adaptive treatment strategies of interest. By emphasizing the intuitive appeal and straightforward implementation of these methods and illustrating the …
Age-Specific Prevalence And Years Of Healthy Life In A System With 3 Health States, Paula Diehr
Age-Specific Prevalence And Years Of Healthy Life In A System With 3 Health States, Paula Diehr
Paula Diehr
Consider a 3-state system with one absorbing state, such as Healthy, Sick, and Dead. Over time, the prevalence of the Healthy state will approach an 'equilibrium' value that is independent of the initial conditions. We derived this equilibrium prevalence (Prev:Equil) as a function of the local transition probabilities. We then used Prev:Equil to estimate the expected number of years spent in the healthy state over time. This estimate is similar to the one calculated by multi-state life table methods, and has the advantage of having an associated standard error. In longitudinal data for older adults, the standard error was accurate …
Functional Principal Component Regression And Functional Partial Least Squares, Philip T. Reiss, R. Todd Ogden
Functional Principal Component Regression And Functional Partial Least Squares, Philip T. Reiss, R. Todd Ogden
Philip T. Reiss
Regression of a scalar response on signal predictors, such as near-infrared (NIR) spectra of chemical samples, presents a major challenge when, as is typically the case, the dimension of the signals far exceeds their number. Most solutions to this problem reduce the dimension of the predictors either by regressing on components--e.g. principal component regression (PCR) and partial least squares (PLS)--or by smoothing methods which restrict the coefficient function to the span of a spline basis. This paper introduces functional versions of PCR and PLS, which combine both of the above dimension reduction approaches. Two versions of functional PCR are developed, …
Biomarker Discovery Using Targeted Maximum Likelihood Estimation: Application To The Treatment Of Antiretroviral Resistant Hiv Infection, Oliver Bembom, Maya L. Petersen, Soo-Yon Rhee, W. Jeffrey Fessel, Sandra E. Sinisi, Robert W. Shafer, Mark J. Van Der Laan
Biomarker Discovery Using Targeted Maximum Likelihood Estimation: Application To The Treatment Of Antiretroviral Resistant Hiv Infection, Oliver Bembom, Maya L. Petersen, Soo-Yon Rhee, W. Jeffrey Fessel, Sandra E. Sinisi, Robert W. Shafer, Mark J. Van Der Laan
Oliver Bembom
Researchers in clinical science and bioinformatics frequently aim to learn which of a set of candidate biomarkers is important in determining a given outcome, and to rank the contributions of the candidates accordingly. This article introduces a new approach to research questions of this type, based on targeted maximum likelihood estimation of variable importance measures. The methodology is illustrated using an example drawn from the treatment of HIV infection. Specifically, given a list of candidate mutations in the protease enzyme of HIV, we aim to discover mutations that reduce clinical virologic response to antiretroviral regimens containing the protease inhibitor lopinavir. …
Data-Adaptive Estimation Of The Treatment-Specific Mean, Yue Wang, Oliver Bembom, Mark Van Der Laan
Data-Adaptive Estimation Of The Treatment-Specific Mean, Yue Wang, Oliver Bembom, Mark Van Der Laan
Oliver Bembom
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 counterfactual 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 …
A Large-Scale Rheumatoid Arthritis Genetic Study Identifies Association At Chr 9q33.2, Steven J. Schrodi
A Large-Scale Rheumatoid Arthritis Genetic Study Identifies Association At Chr 9q33.2, Steven J. Schrodi
Steven J Schrodi
No abstract provided.
Estimating The Effect Of Vigorous Physical Activity On Mortality In The Elderly Based On Realistic Individualized Treatment And Intention-To-Treat Rules, Oliver Bembom, Mark J. Van Der Laan
Estimating The Effect Of Vigorous Physical Activity On Mortality In The Elderly Based On Realistic Individualized Treatment And Intention-To-Treat Rules, 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 …
Analyzing Sequentially Randomized Trials Based On Causal Effect Models For Realistic Individualized Treatment Rules, Oliver Bembom, Mark J. Van Der Laan
Analyzing Sequentially Randomized Trials Based On Causal Effect Models For Realistic Individualized Treatment Rules, Oliver Bembom, Mark J. Van Der Laan
Oliver Bembom
In this paper, we argue that causal effect models for realistic individualized treatment rules represent an attractive tool for analyzing sequentially randomized trials. Unlike a number of methods proposed previously, this approach does not rely on the assumption that intermediate outcomes are discrete or that models for the distributions of these intermediate outcomes given the observed past are correctly specified. In addition, it generalizes the methodology for performing pairwise comparisons between individualized treatment rules by allowing the user to posit a marginal structural model for all candidate treatment rules simultaneously. If only a small number of candidate treatment rules are …
Supervised Detection Of Conserved Motifs In Dna Sequences With Cosmo, Oliver Bembom, Sunduz Keles, Mark J. Van Der Laan
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
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 …
Pre-Processing Mass Spectrometry Data, Kevin R. Coombes, Keith A. Baggerly, Jeffrey S. Morris
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
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
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
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
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 …
Software To Forecast The Global Burden Of Alzheimer's Disease, Ron Brookmeyer, Elizabeth Johnson, Kathryn Ziegler-Graham, H. Michael Arrighi
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
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
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
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 …