Physical Sciences and Mathematics 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.

Correction: Using Participatory Design To Develop (Public) Health Decision Support Systems Through Gis, S. Michelle Driedger, Anita Kothari, Jason Morrison, Michael Sawada, Eric J. Crighton, Ian D. Graham

Anita Kothari

Background: Organizations that collect substantial data for decision-making purposes are often characterized as being 'data rich' but 'information poor'. Maps and mapping tools can be very useful for research transfer in converting locally collected data into information. Challenges involved in incorporating GIS applications into the decision-making process within the non-profit (public) health sector include a lack of financial resources for software acquisition and training for nonspecialists to use such tools. This on-going project has two primary phases. This paper critically reflects on Phase 1: the participatory design (PD) process of developing a collaborative web-based GIS tool.

Methods: A case study …

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 …

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 …

Alien Crustacean Decapods From The Aegean Coast Of Turkey, M. Baki Yokes, S. Ünsal Karhan, Erdogan Okus, Ahsen Yüksek, Asli Aslan, I. Noyan Yilmaz, Nazli Demirel, Volkan Demir, Bella S. Galil

Asli Aslan

Thirty of the 33 alien decapod crustacean species that have been reported off the Turkish Mediterranean coast are believed to have invaded the region via the Suez Canal, but only three of the species have been recorded along the Turkish Aegean coast. The marine biota of Gökova Bay, Datça Peninsula and Gulf of Fethiye, on the southern Aegean coast of Turkey, was studied by diving between 2002 and 2006. Of the eight Erythrean alien decapod species collected there, five constitute new records for the Aegean Sea and three are newly recorded from the Turkish coast of the Aegean Sea.

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

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 …

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 …

High-Loading Nanosized Micelles Of Copoly(Styrene-Maleic Acid)-Zinc Protoporphyrin For Targeted Delivery Of A Potent Heme Oxygenase Inhibitor., Arun Iyer

Arun Iyer

Amphiphilic styrene-maleic acid (SMA) copolymer efficiently formed micelles with a potent heme oxygenase inhibitor-zinc protoporphyrin (ZnPP). The micelles were constructed by subtle pH adjustments to form non-covalent interaction between the hydrophobic ZnPP and amphiphilic SMA. The micelles (SMA-ZnPP) thus formed were nanoparticles with narrow size distribution in water (mean diameter 176.5nm), having tunable loading (from 15% to 60% w/w of ZnPP) with remarkable aqueous solubility. SMA-ZnPP had an average molecular size of 144kDa as determined by size-exclusion chromatography (SEC), this size is a marked increase from the molecular weight of free ZnPP (626.03Da), suggesting the formation of micellar structure. The …

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 …

Contamination Levels Of Selected Organochlorine And Organophosphate Pesticides In The Selangor River, Malaysia Between 2002 To 2003, Kok Hoong Leong

Kok Hoong Leong

In Malaysia, rivers are the main source of public water supplies. This study was conducted from 2002 to 2003 to determine the levels of selected organochlorine and organophosphate pesticides in the Selangor River in Malaysia. Surface water samples have been collected seasonally from nine sites along the river. A liquid–liquid extraction followed by gas chromatography–mass spectrometry technique was used to determine the trace levels of these pesticide residues. The organochlorine pesticides detected were lindane, heptachlor, endosulfan, dieldrin, endosulfan sulfate, o,p′-DDT, p,p′-DDT, o,p′-DDE and p,p′-DDE whereas for organophosphate pesticides, they were chlorpyrifos and diazinon. At the river upstream where a dam …

Why Manage Terminology? Ten Quick Answers, Uwe Muegge

Uwe Muegge

Terminology management is a hot topic these days. At the tcworld conference 2006, terminology had its own forum with hundreds of participants. And a number of highly visible institutions like the LISA Terminology Special Interest Group (SIG) has been evangelizing the development and use of standardized terminology in the business world for many years.

Disciplining Words: What You Always Wanted To Know About Terminology Management, Uwe Muegge

Uwe Muegge

Terminology management enables organizations of any size to use the same terms consistently within and across the communication types that accompany a product or service. Typical communication types include specifications, drawings, GUI, software strings, help systems, technical documentation, marketing materials, regulatory submissions, etc. As multiple authors typically contribute to these communications, terminology management is the most efficient solution for ensuring that the organization speaks with one voice.

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 …

Structure And Thermodynamics Of A Conserved U2 Snrna Domain From Yeast And Human, Dipali G. Sashital, Vincenzo Venditti, Courtney G. Angers, Gabriel Cornilescu, Samuel E. Butcher

Vincenzo Venditti

The spliceosome is a dynamic ribonucleoprotein complex responsible for the removal of intron sequences from pre-messenger RNA. The highly conserved 5′ end of the U2 small nuclear RNA (snRNA) makes key base-pairing interactions with the intron branch point sequence and U6 snRNA. U2 stem I, a stem–loop located in the 5′ region of U2, has been implicated in spliceosome assembly and may modulate the folding of the U2 and U6 snRNAs in the spliceosome active site. Here we present the NMR structures of U2 stem I from human and Saccharomyces cerevisiae. These sequences represent the two major classes of U2 …

Effects Of Support On The Initiation And Duration Of Breastfeeding, Sara L. Gill, Elizabeth Reifsnider, Joseph F. Lucke

Joseph Lucke

Researchers attempted to increase the initiation of breastfeeding and its duration to 6 months among a group of low-income, Hispanic women through an intervention program which included prenatal education and home based postpartum support. All participants were telephoned after delivery to determine infant feeding method. Duration of breastfeeding was determined by counting the number of days from initiation to the last day the baby was put to the breast. The Bayesian approach was used for the statistical analyses. In the intervention group, the propensity to initiate breastfeeding exceeded that of the control group. Results indicate the intervention group had twice …

Controlled Language: The Next Big Thing In Translation?, Uwe Muegge

Uwe Muegge

Many global organizations are beginning to see the productivity indicators for their translation and localization processes reach a plateau. That’s an inevitable fact even for those organizations that use what’s currently billed as the latest and greatest in translation technology, such as translation memory with automated workflow components or globalization management systems. Even with these tools in place, making content available in multiple languages remains a very expensive and time-consuming proposition. For those looking for ways to reduce the cost of translation to the point where almost all materials that should be translation actually can be translated, controlled language may …

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 …