Medicine and Health Sciences Commons^™

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

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

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

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

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 …

The Potential Role Of Probiotics In Reducing Poverty-Associated Infections In Developing Countries, Kingsley C. Anukam

Kingsley C Anukam

Probiotics are defined by the Food and Agricultural Organization/ World Health Organization as “live microorganisms which when administered in adequate amounts confer a health benefit on the host” [1]. The potential benefits of their use have not been adequately investigated, especially in the developing world. Japan introduced Yakult, a probiotic fermented food drink in 1935, and in the Northern hemisphere, research and use of probiotics has gained an unprecedented momentum in the last decade [2]. Use of probiotics is not uncommon in Europe [3], but in many developing countries use of probiotics in its present definition is a foreign concept. …

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 …

A Role For The Forebrain In Mediating Time-Of-Day Differences In Glucocorticoid Counterregulatory Responses To Hypoglycemia In Rats, Lori M. Gorton, Arshad M. Khan, Maryann Bohland, Graciela Sanchez-Watts, Casey M. Donovan, Alan G. Watts

Arshad M. Khan, Ph.D.

No abstract provided.

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, …

Antiviral Activity Of Aloe Vera Against Herpes Simplex Virus Type 2: An In Vitro Study, Keivan Zandi

Keivan Zandi

In this study we tested the antiviral activity of a crude hot glycerine extract of Aloe vera gel which was grown in Bushehr (Southwest of Iran) against HSV-2 replication in Vero cell line. The extract showed antiviral activity against HSV-2 not only before attachment and entry of virus to the Vero cells but also on post attachment stages of virus replication. The IC50 before attachment and entry of virus to the cells is 428 mu g/ml and the CC50 value which is the cytotoxicity of the extract for Vero cells is 3238 mu g/ml, while the calculated selectivity index (SI) …

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. …

Meta-Analysis Evidence Of A Differential Risk Of The Fcrl3 -169t->C Polymorphism In White And East Asian Rheumatoid Arthritis Patients, Steven J. Schrodi, Begovich Ann, Chang Monica

Steven J Schrodi

Association between a functional promoter polymorphism (rs7528684) in the Fc receptor-like gene, FCRL3, and rheumatoid arthritis (RA) has been observed in 3 independent Japanese case-control sample sets ([1][2]). Studies examining the role of this polymorphism in risk of RA in 9 independent white sample sets, however, have yielded conflicting results ([3-8]). Further, a large study of Korean subjects failed to demonstrate association of this single-nucleotide polymorphism (SNP) with RA ([9]). Although the precise function of FCRL3, which has strong structural homology with the classic Fc receptors, is unknown, the existing data are consistent with the hypothesis that it may influence …

Catecholaminergic Control Of Mitogen-Activated Protein Kinase Signaling In Paraventricular Neuroendocrine Neurons In Vivo And In Vitro: A Proposed Role During Glycemic Challenges, Arshad M. Khan, Todd A. Ponzio, Graciela Sanchez-Watts, B. Glenn Stanley, Glenn I. Hatton, Alan G. Watts

Arshad M. Khan, Ph.D.

No abstract provided.

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

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

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

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 …

The Neuropharmacology Of The Ketogenic Diet, Adam Hartman, Maciej Gasior, Elaine Vining, Michael Rogawski

Michael A. Rogawski

The ketogenic diet is a valuable therapeutic approach for epilepsy, one in which most clinical experience has been with children. Although the mechanism by which the diet protects against seizures is unknown, there is evidence that it causes effects on intermediary metabolism that influence the dynamics of the major inhibitory and excitatory neurotransmitter systems in brain. The pattern of protection of the ketogenic diet in animal models of seizures is distinct from that of other anticonvulsants, suggesting that it has a unique mechanism of action. During consumption of the ketogenic diet, marked alterations in brain energy metabolism occur, with ketone …

High-Dose Pralidoxime For Organophosphorus Poisoning, Ashish Goel, Praveen Aggarwal, Sanjeev Bhoi, Vineet Gupta

Vineet Gupta, MD, FACP

No abstract provided.

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 …

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 …

Ethnic Variations In Paraoxonase1 Polymorphism In The Malaysian Population, Rozaida @ Poh Yuen Ying

Rozaida @ Poh Yuen Ying

The role of high-density lipoprotein associated paraoxonase (PON) 1 in protection against oxidative stress associated with the development of complications in diabetes mellitus has been reported. Variations in the PON1 gene, 55LM and 192QR have been described in different populations. These variations are known to be risk factors for heart disease, especially the L and R alleles. We have investigated the prevalence of both polymorphisms in the Malaysian population comprising the three major ethnic groups: Malay, Chinese and Indian, using polymerase chain reaction followed by restriction endonuclease digestion. The results show the pooled frequencies of L and R alleles were …

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 …

Input Vs. Output Level Coupling Demonstrates Asymmetrical Attentional Biases, Gavin Buckingham, David Carey

Gavin Buckingham

The current study examined the performance of each limb as it reached across the body (the hard task), while yoked to it’s ipsilateral reaching counterpart (the easy task).

Epilepsy: Mechanisms Of Drug Action And Clinical Treatment, William Theodore, Michael Rogawski

Michael A. Rogawski

No abstract provided.

Asymmetries In Attention Toward The Dominant Hand: Input Or Output?, Gavin Buckingham, Julie Main, David Carey

Gavin Buckingham

Peters (1981) suggested that an asymmetrical bias in attention (toward the right hand of right handers) could account for many manual asymmetries in bimanual task performance. Support for this notion comes from Honda (1982), who demonstrated preferential monitoring of the dominant hand during a bimanual reaching task, while Buckingham and Carey (2007) observed shorter refractory periods (dwell time in a bimanual discontinuous double-step reaching task) for the right hand.

Recent evidence may indicate an intentional (i.e. selection related behaviour – motor attention) bias toward the dominant hand (Bestelmeyer & Carey, 2004). The current study tests the hypothesis that the right …