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Catherine M. Stein

Bio: Catherine M. Stein is an academic researcher from Case Western Reserve University. The author has contributed to research in topics: Tuberculosis & Mycobacterium tuberculosis. The author has an hindex of 31, co-authored 104 publications receiving 5892 citations. Previous affiliations of Catherine M. Stein include University Hospitals of Cleveland & Makerere University.


Papers
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Book ChapterDOI
TL;DR: The theory of SEM, which allows for the analysis of independent observations for both unrelated and family data, the available software for SEM, and an example of SEM analysis are reviewed.
Abstract: Structural equation modeling (SEM) is a multivariate statistical framework that is used to model complex relationships between directly observed and indirectly observed (latent) variables. SEM is a general framework that involves simultaneously solving systems of linear equations and encompasses other techniques such as regression, factor analysis, path analysis, and latent growth curve modeling. Recently, SEM has gained popularity in the analysis of complex genetic traits because it can be used to better analyze the relationships between correlated variables (traits), to model genes as latent variables as a function of multiple observed genetic variants, and to assess the association between multiple genetic variants and multiple correlated phenotypes of interest. Though the general SEM framework only allows for the analysis of independent observations, recent work has extended SEM for the analysis of data on general pedigrees. Here, we review the theory of SEM for both unrelated and family data, describe the available software for SEM, and provide examples of SEM analysis.

4,203 citations

Journal ArticleDOI
TL;DR: Simmons and colleagues discuss potential mechanisms underlying this resistance, such as those mediated by macrophages, T cells and B cells, and how an understanding of these mechanisms might aid in the development of therapies for tuberculosis.
Abstract: Mycobacterium tuberculosis is a leading cause of mortality worldwide and establishes a long-lived latent infection in a substantial proportion of the human population. Multiple lines of evidence suggest that some individuals are resistant to latent M. tuberculosis infection despite long-term and intense exposure, and we term these individuals ‘resisters’. In this Review, we discuss the epidemiological and genetic data that support the existence of resisters and propose criteria to optimally define and characterize the resister phenotype. We review recent insights into the immune mechanisms of M. tuberculosis clearance, including responses mediated by macrophages, T cells and B cells. Understanding the cellular mechanisms that underlie resistance to M. tuberculosis infection may reveal immune correlates of protection that could be utilized for improved diagnostics, vaccine development and novel host-directed therapeutic strategies. Resisters are individuals who show resistance to infection despite long-term, high exposure to Mycobacterium tuberculosis. In this Review, Simmons and colleagues discuss potential mechanisms underlying this resistance, such as those mediated by macrophages, T cells and B cells, and how an understanding of these mechanisms might aid in the development of therapies for tuberculosis.

180 citations

Journal ArticleDOI
19 Feb 2007-AIDS
TL;DR: Rapid progression of HIV-1 infection was associated with TLR9 polymorphisms, and this association has potential implications for intervention strategies and vaccine developments.
Abstract: BACKGROUND: The clinical course of HIV-1 infection is highly variable among individuals, at least in part as a result of genetic polymorphisms in the host. Toll-like receptors (TLRs) have a key role in innate immunity and mutations in the genes encoding these receptors have been associated with increased or decreased susceptibility to infections. OBJECTIVES: To determine whether single-nucleotide polymorphisms (SNPs) in TLR2-4 and TLR7-9 influenced the natural course of HIV-1 infection. METHODS: Twenty-eight SNPs in TLRs were analysed in HAART-naive HIV-positive patients from the Swiss HIV Cohort Study. The SNPs were detected using Sequenom technology. Haplotypes were inferred using an expectation-maximization algorithm. The CD4 T cell decline was calculated using a least-squares regression. Patients with a rapid CD4 cell decline, less than the 15th percentile, were defined as rapid progressors. The risk of rapid progression associated with SNPs was estimated using a logistic regression model. Other candidate risk factors included age, sex and risk groups (heterosexual, homosexual and intravenous drug use). RESULTS: Two SNPs in TLR9 (1635A/G and +1174G/A) in linkage disequilibrium were associated with the rapid progressor phenotype: for 1635A/G, odds ratio (OR), 3.9 [95% confidence interval (CI),1.7-9.2] for GA versus AA and OR, 4.7 (95% CI,1.9-12.0) for GG versus AA (P = 0.0008). CONCLUSION: Rapid progression of HIV-1 infection was associated with TLR9 polymorphisms. Because of its potential implications for intervention strategies and vaccine developments, additional epidemiological and experimental studies are needed to confirm this association.

156 citations

Journal ArticleDOI
TL;DR: A cohort of Ugandan individuals who were household contacts of patients with TB are reported, revealing a distinctive adaptive immune profile among Mtb-exposed subjects, supporting an expanded definition of the host response to Mtb exposure, with implications for public health and the design of clinical trials.
Abstract: Exposure to Mycobacterium tuberculosis (Mtb) results in heterogeneous clinical outcomes including primary progressive tuberculosis and latent Mtb infection (LTBI). Mtb infection is identified using the tuberculin skin test and interferon-γ (IFN-γ) release assay IGRA, and a positive result may prompt chemoprophylaxis to prevent progression to tuberculosis. In the present study, we report on a cohort of Ugandan individuals who were household contacts of patients with TB. These individuals were highly exposed to Mtb but tested negative by IFN-γ release assay and tuberculin skin test, ‘resisting’ development of classic LTBI. We show that ‘resisters’ possess IgM, class-switched IgG antibody responses and non-IFN-γ T cell responses to the Mtb-specific proteins ESAT6 and CFP10, immunologic evidence of exposure to Mtb. Compared to subjects with classic LTBI, ‘resisters’ display enhanced antibody avidity and distinct Mtb-specific IgG Fc profiles. These data reveal a distinctive adaptive immune profile among Mtb-exposed subjects, supporting an expanded definition of the host response to Mtb exposure, with implications for public health and the design of clinical trials. New immune biomarkers of exposure to tuberculosis may require a rethink of evidence of Mycobacterium tuberculosis infection and control.

155 citations

Journal ArticleDOI
TL;DR: In this paper, the authors explored common genetic influences on speech-sound disorder and reading, and examined linkage for several quantitative traits to markers in the pericentrometric region of chromosome 3 in 77 families ascertained through a child with SSD.
Abstract: Speech-sound disorder (SSD) is a complex behavioral disorder characterized by speech-sound production errors associated with deficits in articulation, phonological processes, and cognitive linguistic processes. SSD is prevalent in childhood and is comorbid with disorders of language, spelling, and reading disability, or dyslexia. Previous research suggests that developmental problems in domains associated with speech and language acquisition place a child at risk for dyslexia. Recent genetic studies have identified several candidate regions for dyslexia, including one on chromosome 3 segregating in a large Finnish pedigree. To explore common genetic influences on SSD and reading, we examined linkage for several quantitative traits to markers in the pericentrometric region of chromosome 3 in 77 families ascertained through a child with SSD. The quantitative scores measured several processes underlying speech-sound production, including phonological memory, phonological representation, articulation, receptive and expressive vocabulary, and reading decoding and comprehension skills. Model-free linkage analysis was followed by identification of sib pairs with linkage and construction of core shared haplotypes. In our multipoint analyses, measures of phonological memory demonstrated the strongest linkage (marker D3S2465, P =5.6×10 −5 , and marker D3S3716, P =6.8×10 −4 ). Tests for single-word decoding also demonstrated linkage (real word reading: marker D3S2465, P =.004; nonsense word reading: marker D3S1595, P =.005). The minimum shared haplotype in sib pairs with similar trait values spans 4.9 cM and is bounded by markers D3S3049 and D3S3045. Our results suggest that domains common to SSD and dyslexia are pleiotropically influenced by a putative quantitative trait locus on chromosome 3.

140 citations


Cited by
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Journal Article
TL;DR: This book by a teacher of statistics (as well as a consultant for "experimenters") is a comprehensive study of the philosophical background for the statistical design of experiment.
Abstract: THE DESIGN AND ANALYSIS OF EXPERIMENTS. By Oscar Kempthorne. New York, John Wiley and Sons, Inc., 1952. 631 pp. $8.50. This book by a teacher of statistics (as well as a consultant for \"experimenters\") is a comprehensive study of the philosophical background for the statistical design of experiment. It is necessary to have some facility with algebraic notation and manipulation to be able to use the volume intelligently. The problems are presented from the theoretical point of view, without such practical examples as would be helpful for those not acquainted with mathematics. The mathematical justification for the techniques is given. As a somewhat advanced treatment of the design and analysis of experiments, this volume will be interesting and helpful for many who approach statistics theoretically as well as practically. With emphasis on the \"why,\" and with description given broadly, the author relates the subject matter to the general theory of statistics and to the general problem of experimental inference. MARGARET J. ROBERTSON

13,333 citations

Journal ArticleDOI
TL;DR: The authors conclude that PLS-SEM path modeling, if appropriately applied, is indeed a "silver bullet" for estimating causal models in many theoretical models and empirical data situations.
Abstract: Structural equation modeling (SEM) has become a quasi-standard in marketing and management research when it comes to analyzing the cause-effect relations between latent constructs. For most researchers, SEM is equivalent to carrying out covariance-based SEM (CB-SEM). While marketing researchers have a basic understanding of CB-SEM, most of them are only barely familiar with the other useful approach to SEM-partial least squares SEM (PLS-SEM). The current paper reviews PLS-SEM and its algorithm, and provides an overview of when it can be most appropriately applied, indicating its potential and limitations for future research. The authors conclude that PLS-SEM path modeling, if appropriately applied, is indeed a "silver bullet" for estimating causal models in many theoretical models and empirical data situations.

11,624 citations

Journal Article
TL;DR: For the next few weeks the course is going to be exploring a field that’s actually older than classical population genetics, although the approach it’ll be taking to it involves the use of population genetic machinery.
Abstract: So far in this course we have dealt entirely with the evolution of characters that are controlled by simple Mendelian inheritance at a single locus. There are notes on the course website about gametic disequilibrium and how allele frequencies change at two loci simultaneously, but we didn’t discuss them. In every example we’ve considered we’ve imagined that we could understand something about evolution by examining the evolution of a single gene. That’s the domain of classical population genetics. For the next few weeks we’re going to be exploring a field that’s actually older than classical population genetics, although the approach we’ll be taking to it involves the use of population genetic machinery. If you know a little about the history of evolutionary biology, you may know that after the rediscovery of Mendel’s work in 1900 there was a heated debate between the “biometricians” (e.g., Galton and Pearson) and the “Mendelians” (e.g., de Vries, Correns, Bateson, and Morgan). Biometricians asserted that the really important variation in evolution didn’t follow Mendelian rules. Height, weight, skin color, and similar traits seemed to

9,847 citations

Journal ArticleDOI
06 Jun 1986-JAMA
TL;DR: The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or her own research.
Abstract: I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

7,563 citations

Journal ArticleDOI
TL;DR: An extensive search in the 30 top ranked marketing journals allowed us to identify 204 PLS-SEM applications published in a 30-year period (1981 to 2010), and a critical analysis of these articles addresses the following key methodological issues: reasons for using PLS, data and model characteristics, outer and inner model evaluations, and reporting.
Abstract: Most methodological fields undertake regular critical reflections to ensure rigorous research and publication practices, and, consequently, acceptance in their domain. Interestingly, relatively little attention has been paid to assessing the use of partial least squares structural equation modeling (PLS-SEM) in marketing research—despite its increasing popularity in recent years. To fill this gap, we conducted an extensive search in the 30 top ranked marketing journals that allowed us to identify 204 PLS-SEM applications published in a 30-year period (1981 to 2010). A critical analysis of these articles addresses, amongst others, the following key methodological issues: reasons for using PLS-SEM, data and model characteristics, outer and inner model evaluations, and reporting. We also give an overview of the interdependencies between researchers’ choices, identify potential problem areas, and discuss their implications. On the basis of our findings, we provide comprehensive guidelines to aid researchers in avoiding common pitfalls in PLS-SEM use. This study is important for researchers and practitioners, as PLS-SEM requires several critical choices that, if not made correctly, can lead to improper findings, interpretations, and conclusions.

5,328 citations