TY - JOUR
TI - Recent developments in bootstrap methods for dependent data
AU - Cavaliere, Giuseppe
AU - Politis, Dimitris N
AU - Rahbek, Anders
AU - Bertail, Patrice
AU - Clémençon, Stéphan
AU - Tressou, Jessica
AU - others
T2 - Journal of Time Series Analysis
DA - 2015///
PY - 2015///
VL - 36
IS - 3
SP - 462-480
ER -
TY - JOUR
TI - The dependent random weighting
AU - Sengupta, Srijan
AU - Shao, Xiaofeng
AU - Wang, Yingchuan
T2 - Journal of Time Series Analysis
DA - 2015///
PY - 2015///
VL - 36
IS - 3
SP - 315-326
ER -
TY - JOUR
TI - Spectral clustering in heterogeneous networks
AU - Sengupta, Srijan
AU - Chen, Yuguo
T2 - Statistica Sinica
DA - 2015///
PY - 2015///
SP - 1081-1106
ER -
TY - JOUR
TI - Restricted spatial regression in practice: geostatistical models, confounding, and robustness under model misspecification
AU - Hanks, Ephraim M.
AU - Schliep, Erin M.
AU - Hooten, Mevin B.
AU - Hoeting, Jennifer A.
T2 - Environmetrics
AB - In spatial generalized linear mixed models (SGLMMs), covariates that are spatially smooth are often collinear with spatially smooth random effects. This phenomenon is known as spatial confounding and has been studied primarily in the case where the spatial support of the process being studied is discrete (e.g., areal spatial data). In this case, the most common approach suggested is restricted spatial regression (RSR) in which the spatial random effects are constrained to be orthogonal to the fixed effects. We consider spatial confounding and RSR in the geostatistical (continuous spatial support) setting. We show that RSR provides computational benefits relative to the confounded SGLMM, but that Bayesian credible intervals under RSR can be inappropriately narrow under model misspecification. We propose a posterior predictive approach to alleviating this potential problem and discuss the appropriateness of RSR in a variety of situations. We illustrate RSR and SGLMM approaches through simulation studies and an analysis of malaria frequencies in The Gambia, Africa. Copyright © 2015 John Wiley & Sons, Ltd.
DA - 2015/2/18/
PY - 2015/2/18/
DO - 10.1002/env.2331
VL - 26
IS - 4
SP - 243-254
J2 - Environmetrics
LA - en
OP -
SN - 1180-4009 1099-095X
UR - http://dx.doi.org/10.1002/env.2331
DB - Crossref
KW - generalized linear mixed model
KW - spatial confounding
KW - random effects
KW - restricted regression
ER -
TY - JOUR
TI - Data augmentation and parameter expansion for independent or spatially correlated ordinal data
AU - Schliep, Erin M.
AU - Hoeting, Jennifer A.
T2 - Computational Statistics & Data Analysis
AB - Data augmentation and parameter expansion can lead to improved iterative sampling algorithms for Markov chain Monte Carlo (MCMC). Data augmentation allows for simpler and more feasible simulation from a posterior distribution. Parameter expansion accelerates convergence of iterative sampling algorithms by increasing the parameter space. Data augmentation and parameter-expanded data augmentation MCMC algorithms are proposed for fitting probit models for independent ordinal response data. The algorithms are extended for fitting probit linear mixed models for spatially correlated ordinal data. The effectiveness of data augmentation and parameter-expanded data augmentation is illustrated using the probit model and ordinal response data, however, the approach can be used broadly across model and data types.
DA - 2015/10//
PY - 2015/10//
DO - 10.1016/j.csda.2015.03.020
VL - 90
SP - 1-14
J2 - Computational Statistics & Data Analysis
LA - en
OP -
SN - 0167-9473
UR - http://dx.doi.org/10.1016/j.csda.2015.03.020
DB - Crossref
KW - Data augmentation
KW - Parameter expansion
KW - Ordinal data
KW - Probit model
KW - Spatial correlation
ER -
TY - JOUR
TI - Stochastic Modeling for Velocity of Climate Change
AU - Schliep, Erin M.
AU - Gelfand, Alan E.
AU - Clark, James S.
T2 - Journal of Agricultural, Biological, and Environmental Statistics
DA - 2015/6/16/
PY - 2015/6/16/
DO - 10.1007/s13253-015-0210-9
VL - 20
IS - 3
SP - 323-342
J2 - JABES
LA - en
OP -
SN - 1085-7117 1537-2693
UR - http://dx.doi.org/10.1007/s13253-015-0210-9
DB - Crossref
KW - Climate velocity
KW - Directional derivatives
KW - Gaussian spatial processes
ER -
TY - JOUR
TI - Modeling change in forest biomass across the eastern US
AU - Schliep, Erin M.
AU - Gelfand, Alan E.
AU - Clark, James S.
AU - Zhu, Kai
T2 - Environmental and Ecological Statistics
DA - 2015/6/27/
PY - 2015/6/27/
DO - 10.1007/s10651-015-0321-z
VL - 23
IS - 1
SP - 23-41
J2 - Environ Ecol Stat
LA - en
OP -
SN - 1352-8505 1573-3009
UR - http://dx.doi.org/10.1007/s10651-015-0321-z
DB - Crossref
KW - Allometric equations
KW - Bayesian hierarchical model
KW - Cumulative uncertainty
KW - Forest biomass
ER -
TY - JOUR
TI - A data fusion approach for spatial analysis of speciated PM2.5across time
AU - Rundel, Colin W.
AU - Schliep, Erin M.
AU - Gelfand, Alan E.
AU - Holland, David M.
T2 - Environmetrics
AB - PM 2.5 exposure is linked to a number of adverse health effects such as lung cancer and cardiovascular disease. However, PM 2.5 is a complex mixture of different species whose composition varies substantially in both space and time. An open question is how these constituent species contribute to the overall negative health outcomes seen from PM 2.5 exposure. To this end, the Environmental Protection Agency as well as other federal, state, and local organization monitor total PM 2.5 along with its primary species on a national scale. From an epidemiological perspective, there is a need to develop effective methods that will allow for the spatially and temporally sparse observations to be used to predict exposures for locations across the entire United States. Toward this objective, we have collected data from three separate monitoring station networks as well as output from a deterministic atmospheric computer model. We introduce a novel multi‐level speciated PM 2.5 model, which captures the following features: (1) it fuses data from three monitoring networks; (2) it simultaneously models each of the five primary components of PM 2.5 from each network along with the computer model output; (3) it introduces species and network level measurement error models as well as total PM 2.5 measurement error models, all varying around the respective latent true levels; (4) it incorporates an unobserved “other” species component as well as a sum constraint such that the total is physically consistent (i.e., total must be equal to the sum of the primary species and “other”), which is not always the case with the observed data. Copyright © 2015 John Wiley & Sons, Ltd.
DA - 2015/10/26/
PY - 2015/10/26/
DO - 10.1002/env.2369
VL - 26
IS - 8
SP - 515-525
J2 - Environmetrics
LA - en
OP -
SN - 1180-4009
UR - http://dx.doi.org/10.1002/env.2369
DB - Crossref
KW - downscaling
KW - latent process
KW - Markov chain Monte Carlo
KW - multi-level model
KW - tobit (truncated) Gaussian process
ER -
TY - JOUR
TI - Autoregressive spatially varying coefficients model for predicting daily PM<sub>2.5</sub> using VIIRS satellite AOT
AU - Schliep, E. M.
AU - Gelfand, A. E.
AU - Holland, D. M.
T2 - Advances in Statistical Climatology, Meteorology and Oceanography
AB - Abstract. There is considerable demand for accurate air quality information in human health analyses. The sparsity of ground monitoring stations across the United States motivates the need for advanced statistical models to predict air quality metrics, such as PM2.5, at unobserved sites. Remote sensing technologies have the potential to expand our knowledge of PM2.5 spatial patterns beyond what we can predict from current PM2.5 monitoring networks. Data from satellites have an additional advantage in not requiring extensive emission inventories necessary for most atmospheric models that have been used in earlier data fusion models for air pollution. Statistical models combining monitoring station data with satellite-obtained aerosol optical thickness (AOT), also referred to as aerosol optical depth (AOD), have been proposed in the literature with varying levels of success in predicting PM2.5. The benefit of using AOT is that satellites provide complete gridded spatial coverage. However, the challenges involved with using it in fusion models are (1) the correlation between the two data sources varies both in time and in space, (2) the data sources are temporally and spatially misaligned, and (3) there is extensive missingness in the monitoring data and also in the satellite data due to cloud cover. We propose a hierarchical autoregressive spatially varying coefficients model to jointly model the two data sources, which addresses the foregoing challenges. Additionally, we offer formal model comparison for competing models in terms of model fit and out of sample prediction of PM2.5. The models are applied to daily observations of PM2.5 and AOT in the summer months of 2013 across the conterminous United States. Most notably, during this time period, we find small in-sample improvement incorporating AOT into our autoregressive model but little out-of-sample predictive improvement.
DA - 2015/12/16/
PY - 2015/12/16/
DO - 10.5194/ascmo-1-59-2015
VL - 1
IS - 1
SP - 59-74
J2 - Adv. Stat. Clim. Meteorol. Oceanogr.
LA - en
OP -
SN - 2364-3587
UR - http://dx.doi.org/10.5194/ascmo-1-59-2015
DB - Crossref
ER -
TY - CONF
TI - A Collaborative Approach to Voluntary Watershed Restoration in Coastal North Carolina
AU - Carey, Erin S.
AU - Page, Jonathan L.
AU - Shew, Roger D.
AU - Hunt, III, William F.
T2 - International Low Impact Development 2015
AB - The Cape Fear region in North Carolina has long been recognized for its scenic location, clear ocean waters, and productive tidal creeks. Like many coastal communities, an increase in the popularity of this region has resulted in a rush of traditional development over the last four decades. Impervious roads, parking lots, roofs, and sidewalks have replaced pine forests and sandy dunes, and stormwater volumes entering the local tidal creeks have increased dramatically. By the 1980s, water quality in local tidal creeks was in decline. As the decades passed, the local creeks experienced progressive shellfishing closures that have since become typical for the region. By 2010 a vast majority of the waters previously open to shellfishing had been closed permanently, with additional areas open only conditionally and outside of predetermined rain events.
C2 - 2015/1/12/
C3 - International Low Impact Development Conference 2015
DA - 2015/1/12/
DO - 10.1061/9780784479025.041
PB - American Society of Civil Engineers
SN - 9780784479025
UR - http://dx.doi.org/10.1061/9780784479025.041
DB - Crossref
ER -
TY - JOUR
TI - Asymptotically Optimal Nonparametric Empirical Bayes Via Predictive Recursion
AU - Martin, Ryan
T2 - Communications in Statistics - Theory and Methods
AB - An empirical Bayes problem has an unknown prior to be estimated from data. The predictive recursion (PR) algorithm provides fast nonparametric estimation of mixing distributions and is ideally suited for empirical Bayes applications. This article presents a general notion of empirical Bayes asymptotic optimality, and it is shown that PR-based procedures satisfy this property under certain conditions. As an application, the problem of in-season prediction of baseball batting averages is considered. There the PR-based empirical Bayes rule performs well in terms of prediction error and ability to capture the distribution of the latent features.
DA - 2015///
PY - 2015///
DO - 10.1080/03610926.2012.743566
VL - 44
IS - 2
SP - 286–299
SN - 0361-0926 1532-415X
UR - http://dx.doi.org/10.1080/03610926.2012.743566
KW - Batting average
KW - Compound decision problem
KW - Density estimation
KW - High-dimensional
KW - Mixture model
ER -
TY - JOUR
TI - Frameworks for prior-free posterior probabilistic inference
AU - Liu, Chuanhai
AU - Martin, Ryan
T2 - Wiley Interdisciplinary Reviews: Computational Statistics
AB - The development of statistical methods for valid and efficient probabilistic inference without prior distributions has a long history. Fisher's fiducial inference is perhaps the most famous of these attempts. We argue that, despite its seemingly prior‐free formulation, fiducial and its various extensions are not prior‐free and, therefore, do not meet the requirements for prior‐free probabilistic inference. In contrast, the inferential model ( IM ) framework is genuinely prior‐free and is shown to be a promising new method for generating both valid and efficient probabilistic inference. With a brief introduction to the two fundamental principles, namely, the validity and efficiency principles, the three‐step construction of the basic IM framework is discussed in the context of the validity principle. Efficient IM methods, based on conditioning and marginalization are illustrated with two benchmark examples, namely, the bivariate normal with unknown correlation coefficient and the Behrens–Fisher problem. WIREs Comput Stat 2015, 7:77–85. doi: 10.1002/wics.1329 This article is categorized under: Statistical and Graphical Methods of Data Analysis > Bayesian Methods and Theory
DA - 2015/1//
PY - 2015/1//
DO - 10.1002/WICS.1329
VL - 7
IS - 1
SP - 77–85
SN - 1939-5108
UR - http://dx.doi.org/10.1002/WICS.1329
KW - Bayes
KW - belief function
KW - fiducial
KW - inferential models
KW - statistical principles
ER -
TY - JOUR
TI - Marginal Inferential Models: Prior-Free Probabilistic Inference on Interest Parameters
AU - Martin, Ryan
AU - Liu, Chuanhai
T2 - Journal of the American Statistical Association
AB - The inferential models (IM) framework provides prior-free, frequency-calibrated, posterior probabilistic inference. The key is the use of random sets to predict unobservable auxiliary variables connected to the observable data and unknown parameters. When nuisance parameters are present, a marginalization step can reduce the dimension of the auxiliary variable which, in turn, leads to more efficient inference. For regular problems, exact marginalization can be achieved, and we give conditions for marginal IM validity. We show that our approach provides exact and efficient marginal inference in several challenging problems, including a many-normal-means problem. In non-regular problems, we propose a generalized marginalization technique and prove its validity. Details are given for two benchmark examples, namely, the Behrens--Fisher and gamma mean problems.
DA - 2015/10/2/
PY - 2015/10/2/
DO - 10.1080/01621459.2014.985827
VL - 110
IS - 512
SP - 1621-1631
J2 - Journal of the American Statistical Association
LA - en
OP -
SN - 0162-1459 1537-274X
UR - http://dx.doi.org/10.1080/01621459.2014.985827
DB - Crossref
KW - Belief
KW - Efficiency
KW - Nuisance parameter
KW - Plausibility
KW - Predictive random set
KW - Validity
ER -
TY - JOUR
TI - Plausibility Functions and Exact Frequentist Inference
AU - Martin, Ryan
T2 - Journal of the American Statistical Association
AB - In the frequentist program, inferential methods with exact control on error rates are a primary focus. The standard approach, however, is to rely on asymptotic approximations, which may not be suitable. This article presents a general framework for the construction of exact frequentist procedures based on plausibility functions. It is shown that the plausibility function-based tests and confidence regions have the desired frequentist properties in finite samples—no large-sample justification needed. An extension of the proposed method is also given for problems involving nuisance parameters. Examples demonstrate that the plausibility function-based method is both exact and efficient in a wide variety of problems.
DA - 2015/10/2/
PY - 2015/10/2/
DO - 10.1080/01621459.2014.983232
VL - 110
IS - 512
SP - 1552-1561
J2 - Journal of the American Statistical Association
LA - en
OP -
SN - 0162-1459 1537-274X
UR - http://dx.doi.org/10.1080/01621459.2014.983232
DB - Crossref
KW - Bootstrap
KW - Confidence region
KW - Hypothesis test
KW - Likelihood
KW - Monte Carlo
KW - p-Value
KW - Profile likelihood
ER -
TY - JOUR
TI - Groupwise Dimension Reduction via Envelope Method
AU - Guo, Zifang
AU - Li, Lexin
AU - Lu, Wenbin
AU - Li, Bing
T2 - Journal of the American Statistical Association
AB - The family of sufficient dimension reduction (SDR) methods that produce informative combinations of predictors, or indices, are particularly useful for high dimensional regression analysis. In many such analyses, it becomes increasingly common that there is available a priori subject knowledge of the predictors; e.g., they belong to different groups. While many recent SDR proposals have greatly expanded the scope of the methods' applicability, how to effectively incorporate the prior predictor structure information remains a challenge. In this article, we aim at dimension reduction that recovers full regression information while preserving the predictor group structure. Built upon a new concept of the direct sum envelope, we introduce a systematic way to incorporate the group information in most existing SDR estimators. As a result, the reduction outcomes are much easier to interpret. Moreover, the envelope method provides a principled way to build a variety of prior structures into dimension reduction analysis. Both simulations and real data analysis demonstrate the competent numerical performance of the new method.
DA - 2015/10/2/
PY - 2015/10/2/
DO - 10.1080/01621459.2014.970687
VL - 110
IS - 512
SP - 1515-1527
J2 - Journal of the American Statistical Association
LA - en
OP -
SN - 0162-1459 1537-274X
UR - http://dx.doi.org/10.1080/01621459.2014.970687
DB - Crossref
KW - Central subspace
KW - Direct sum envelope
KW - Multiple-index models
KW - Sliced inverse regression
ER -
TY - JOUR
TI - Authors' Reply to comments on ‘Sample size calculation for the proportional hazards cure model’
AU - Wang, Songfeng
AU - Zhang, Jiajia
AU - Lu, Wenbin
T2 - Statistics in Medicine
AB - Statistics in MedicineVolume 34, Issue 17 p. 2578-2580 Author's Reply Authors' Reply to comments on ‘Sample size calculation for the proportional hazards cure model’ Songfeng Wang, Songfeng Wang Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, SC, 29208 USASearch for more papers by this authorJiajia Zhang, Jiajia Zhang Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, SC, 29208 USASearch for more papers by this authorWenbin Lu, Wenbin Lu Department of Statistics, North Carolina State University, Raleigh, NC, 27695 USASearch for more papers by this author Songfeng Wang, Songfeng Wang Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, SC, 29208 USASearch for more papers by this authorJiajia Zhang, Jiajia Zhang Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, SC, 29208 USASearch for more papers by this authorWenbin Lu, Wenbin Lu Department of Statistics, North Carolina State University, Raleigh, NC, 27695 USASearch for more papers by this author First published: 01 July 2015 https://doi.org/10.1002/sim.6491Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Volume34, Issue1730 July 2015Pages 2578-2580 RelatedInformation
DA - 2015/7/1/
PY - 2015/7/1/
DO - 10.1002/SIM.6491
VL - 34
IS - 17
SP - 2578-2580
J2 - Statist. Med.
LA - en
OP -
SN - 0277-6715
UR - http://dx.doi.org/10.1002/SIM.6491
DB - Crossref
ER -
TY - SOUND
TI - Bayesian Methods for Reliability, International Workshop on Reliability and Time Series Methodology
AU - Ghosh, S.
DA - 2015///
PY - 2015///
ER -
TY - CONF
TI - Spatio-Temporal Analysis of Total Nitrate Concentrations Using Dynamic Statistical Models
AU - Ghosh, S.
T2 - VI-MSS Workshop on Environmental Statistics, Indian Statistical Institute
C2 - 2015///
CY - Kolkata, India
DA - 2015///
PY - 2015/3/2/
ER -
TY - CONF
TI - Opportunities at SAMSI
AU - Ghosh, S.
T2 - NISS-SAMSI Aliate Annual Meeting at ENAR
C2 - 2015///
CY - Miami, FL
DA - 2015///
PY - 2015/3/15/
ER -
TY - SOUND
TI - High-dimensional Multivariate Imputation Methods for ARMS Data Featuring New Methods for Ordinal Variables
AU - Ghosh, S.
DA - 2015/4/2/
PY - 2015/4/2/
ER -
TY - RPRT
TI - On the estimation of the order of smoothness of the regression function
AU - Taylor-Rodriguez, D.
AU - Ghosh, S.K.
DA - 2015///
PY - 2015///
M1 - 1510.02967
M3 - arXiv preprint
SN - 1510.02967
ER -
TY - SOUND
TI - A exible observed factor model with separate dynamics for the factor volatilities and their correlation matrix
AU - Ghosh, S.
DA - 2015/4/3/
PY - 2015/4/3/
ER -
TY - SOUND
TI - Nonparametric Models for Longitudinal Data Using Bernstein Polynomials
AU - Ghoah, S.
DA - 2015///
PY - 2015///
ER -
TY - CONF
TI - Nonparametric estimation of the conditional mean residual life function
AU - Ghosh, S.
T2 - QPRC-2015
C2 - 2015///
CY - Raleigh, NC
DA - 2015///
PY - 2015/6/10/
ER -
TY - SOUND
TI - Nonparametric Estimation of the Conditional Mean Residual Life Function
AU - Ghosh, S.
DA - 2015/7/17/
PY - 2015/7/17/
ER -
TY - CONF
TI - Analyzing Longitudinal Data Using a Sieve of Bernstein Polynomials
AU - Ghosh, S.
T2 - 60a Reunião Anual da RBras e 16 SEAGRO Presidente Prudente
C2 - 2015///
CY - São Paulo, Brazil
DA - 2015///
PY - 2015/7/20/
ER -
TY - CONF
TI - Using Historical Data in Clinical Trials: A Discussion
AU - Ghosh, S.
T2 - FDA-Industry Statistics Workshop
C2 - 2015///
CY - Washington, DC
DA - 2015///
PY - 2015/9/16/
ER -
TY - CONF
TI - A Statistician's Journey: Atmospheric Sciences to Zoology
AU - Ghosh, S.
T2 - Annual SACNAS Conference
C2 - 2015///
CY - Washington, DC
DA - 2015///
PY - 2015/10/28/
ER -
TY - CONF
TI - Nonparametric Longitudinal Analysis of Irregularly Observed Noisy Data
AU - Ghosh, S.
T2 - Department of Statistics Colloquium Western Michigan University
C2 - 2015/11/13/
CY - Kalamazoo, MI
DA - 2015/11/13/
PY - 2015/11/13/
ER -
TY - CONF
TI - Dynamic Model Based Methods to Test for Biosimilarity
AU - Ghosh, S.
T2 - Ninth International Triennial Calcutta Symposium on Probability and Statistics
C2 - 2015///
CY - Kolkata, India
DA - 2015///
PY - 2015/12/28/
ER -
TY - JOUR
TI - Efficient Sampling Methods for Truncated Multivariate Normal and Student-tDistributions Subject to Linear Inequality Constraints
AU - Li, Yifang
AU - Ghosh, Sujit K.
T2 - Journal of Statistical Theory and Practice
DA - 2015/1/23/
PY - 2015/1/23/
DO - 10.1080/15598608.2014.996690
VL - 9
IS - 4
SP - 712-732
J2 - Journal of Statistical Theory and Practice
LA - en
OP -
SN - 1559-8608 1559-8616
UR - http://dx.doi.org/10.1080/15598608.2014.996690
DB - Crossref
KW - Gibbs sampler
KW - Rejection sampling
KW - Truncated multivariate normal distribution
KW - Truncated multivariate Student-t distribution
KW - Truncated scale mixture of multivariate normal distribution
ER -
TY - JOUR
TI - Synchronized age-related gene expression changes across multiple tissues in human and the link to complex diseases
AU - Yang, Jialiang
AU - Huang, Tao
AU - Petralia, Francesca
AU - Long, Quan
AU - Zhang, Bin
AU - Argmann, Carmen
AU - Zhao, Yong
AU - Mobbs, Charles V.
AU - Schadt, Eric E.
AU - Zhu, Jun
AU - Tu, Zhidong
T2 - Scientific Reports
AB - Aging is one of the most important biological processes and is a known risk factor for many age-related diseases in human. Studying age-related transcriptomic changes in tissues across the whole body can provide valuable information for a holistic understanding of this fundamental process. In this work, we catalogue age-related gene expression changes in nine tissues from nearly two hundred individuals collected by the Genotype-Tissue Expression (GTEx) project. In general, we find the aging gene expression signatures are very tissue specific. However, enrichment for some well-known aging components such as mitochondria biology is observed in many tissues. Different levels of cross-tissue synchronization of age-related gene expression changes are observed, and some essential tissues (e.g., heart and lung) show much stronger "co-aging" than other tissues based on a principal component analysis. The aging gene signatures and complex disease genes show a complex overlapping pattern and only in some cases, we see that they are significantly overlapped in the tissues affected by the corresponding diseases. In summary, our analyses provide novel insights to the co-regulation of age-related gene expression in multiple tissues; it also presents a tissue-specific view of the link between aging and age-related diseases.
DA - 2015/10/19/
PY - 2015/10/19/
DO - 10.1038/SREP15145
VL - 5
IS - 1
SP - 15145
SN - 2045-2322
UR - http://dx.doi.org/10.1038/SREP15145
ER -
TY - JOUR
TI - Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways
AU - Tzeng, Jung-Ying
T2 - Nature Neuroscience
AB - Better analytical methods are needed to extract biological meaning from genome-wide association studies (GWAS) of psychiatric disorders. Here the authors take GWAS data from over 60,000 subjects, including patients with schizophrenia, bipolar disorder and major depression, and identify common etiological pathways shared amongst them. Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.
DA - 2015/1/19/
PY - 2015/1/19/
DO - 10.1038/NN.3922
VL - 18
IS - 2
SP - 199–209
SN - 1097-6256 1546-1726
UR - http://dx.doi.org/10.1038/NN.3922
ER -
TY - JOUR
TI - Comment
AU - Chatterjee, A.
AU - Lahiri, S. N.
T2 - Journal of the American Statistical Association
DA - 2015/10/2/
PY - 2015/10/2/
DO - 10.1080/01621459.2015.1102143
VL - 110
IS - 512
SP - 1434-1438
J2 - Journal of the American Statistical Association
LA - en
OP -
SN - 0162-1459 1537-274X
UR - http://dx.doi.org/10.1080/01621459.2015.1102143
DB - Crossref
ER -
TY - JOUR
TI - Statistical Methods for Generalized Linear Models with Covariates Subject to Detection Limits
AU - Bernhardt, Paul W.
AU - Wang, Huixia J.
AU - Zhang, Daowen
T2 - Statistics in Biosciences
AB - Censored observations are a common occurrence in biomedical data sets. Although a large amount of research has been devoted to estimation and inference for data with censored responses, very little research has focused on proper statistical procedures when predictors are censored. In this paper, we consider statistical methods for dealing with multiple predictors subject to detection limits within the context of generalized linear models. We investigate and adapt several conventional methods and develop a new multiple imputation approach for analyzing data sets with predictors censored due to detection limits. We establish the consistency and asymptotic normality of the proposed multiple imputation estimator and suggest a computationally simple and consistent variance estimator. We also demonstrate that the conditional mean imputation method often leads to inconsistent estimates in generalized linear models, while several other methods are either computationally intensive or lead to parameter estimates that are biased or more variable compared to the proposed multiple imputation estimator. In an extensive simulation study, we assess the bias and variability of different approaches within the context of a logistic regression model and compare variance estimation methods for the proposed multiple imputation estimator. Lastly, we apply several methods to analyze the data set from a recently-conducted GenIMS study.
DA - 2015/5/24/
PY - 2015/5/24/
DO - 10.1007/S12561-013-9099-4
VL - 7
IS - 1
SP - 68–89
SN - 1867-1764 1867-1772
UR - http://dx.doi.org/10.1007/S12561-013-9099-4
KW - Censored predictor
KW - Complete case
KW - Conditional mean imputation
KW - Detection limit
KW - Improper multiple imputation
ER -
TY - RPRT
TI - Semiparametric estimation of spectral density function for irregular spatial data
AU - Yang, S.
AU - Zhu, Z.
DA - 2015///
PY - 2015///
UR - https://arxiv.org/abs/1508.06886
ER -
TY - JOUR
TI - Erratum: Gene expression in major depressive disorder
AU - Jansen, R
AU - Penninx, B W J H
AU - Madar, V
AU - Xia, K
AU - Milaneschi, Y
AU - Hottenga, J J
AU - Hammerschlag, A R
AU - Beekman, A
AU - van der Wee, N
AU - Smit, J H
AU - Brooks, A I
AU - Tischfield, J
AU - Posthuma, D
AU - Schoevers, R
AU - van Grootheest, G
AU - Willemsen, G
AU - de Geus, E J
AU - Boomsma, D I
AU - Wright, F A
AU - Zou, F
AU - Sun, W
AU - Sullivan, P F
T2 - Molecular Psychiatry
AB - Correction to: Molecular Psychiatry advance online publication, 26 May 2015; doi:10.1038/mp.2015.57 Following publication of the above article, the authors noticed that the Supplementary Figure legends were not published with the paper. The legends accompany this erratum. In addition, the Supplementary Tables were originally presented as PDF files.
DA - 2015/6/23/
PY - 2015/6/23/
DO - 10.1038/MP.2015.94
VL - 21
IS - 3
SP - 444-444
J2 - Mol Psychiatry
LA - en
OP -
SN - 1359-4184 1476-5578
UR - http://dx.doi.org/10.1038/MP.2015.94
DB - Crossref
ER -
TY - JOUR
TI - Gene expression in major depressive disorder
AU - Jansen, R
AU - Penninx, B W J H
AU - Madar, V
AU - Xia, K
AU - Milaneschi, Y
AU - Hottenga, J J
AU - Hammerschlag, A R
AU - Beekman, A
AU - van der Wee, N
AU - Smit, J H
AU - Brooks, A I
AU - Tischfield, J
AU - Posthuma, D
AU - Schoevers, R
AU - van Grootheest, G
AU - Willemsen, G
AU - de Geus, E J
AU - Boomsma, D I
AU - Wright, F A
AU - Zou, F
AU - Sun, W
AU - Sullivan, P F
T2 - Molecular Psychiatry
AB - The search for genetic variants underlying major depressive disorder (MDD) has not yet provided firm leads to its underlying molecular biology. A complementary approach is to study gene expression in relation to MDD. We measured gene expression in peripheral blood from 1848 subjects from The Netherlands Study of Depression and Anxiety. Subjects were divided into current MDD (N=882), remitted MDD (N=635) and control (N=331) groups. MDD status and gene expression were measured again 2 years later in 414 subjects. The strongest gene expression differences were between the current MDD and control groups (129 genes at false-discovery rate, FDR<0.1). Gene expression differences across MDD status were largely unrelated to antidepressant use, inflammatory status and blood cell counts. Genes associated with MDD were enriched for interleukin-6 (IL-6)-signaling and natural killer (NK) cell pathways. We identified 13 gene expression clusters with specific clusters enriched for genes involved in NK cell activation (downregulated in current MDD, FDR=5.8 × 10(-5)) and IL-6 pathways (upregulated in current MDD, FDR=3.2 × 10(-3)). Longitudinal analyses largely confirmed results observed in the cross-sectional data. Comparisons of gene expression results to the Psychiatric Genomics Consortium (PGC) MDD genome-wide association study results revealed overlap with DVL3. In conclusion, multiple gene expression associations with MDD were identified and suggest a measurable impact of current MDD state on gene expression. Identified genes and gene clusters are enriched with immune pathways previously associated with the etiology of MDD, in line with the immune suppression and immune activation hypothesis of MDD.
DA - 2015/5/26/
PY - 2015/5/26/
DO - 10.1038/MP.2015.57
VL - 21
IS - 3
SP - 339-347
J2 - Mol Psychiatry
LA - en
OP -
SN - 1359-4184 1476-5578
UR - http://dx.doi.org/10.1038/MP.2015.57
DB - Crossref
ER -
TY - JOUR
TI - Evaluating Deer Hunters’ Support for Hunting Deer with Dogs
AU - Cook, Merril A.
AU - Peterson, M. Nils
AU - Colter Chitwood, M.
AU - Palmer, Dain
AU - DePerno, Christopher S.
AU - Gross, Kevin
T2 - Human Dimensions of Wildlife
AB - Hunting deer with dogs (dog hunting) has a long tradition in the United States but has created conflict among deer hunters. Our objectives were to determine factors predicting support for dog hunting in North Carolina. Using a 2006 survey of North Carolina deer hunters, we evaluated factors that potentially influenced support for dog hunting (e.g., geographic region, hunting method, perceptions about deer populations and hunter participation, leasing practices). Nearly half (46%) of the deer hunters (n = 5,005) believed dog hunting should be illegal. Most deer hunters who opposed dog hunting neither dog hunted nor hunted in regions where dog hunting had a strong history. Concerns among non–dog hunters mostly focused on competition for deer hunting opportunities. Our results indicate a need to promote greater awareness among the diverse hunting groups and suggest dog hunters may be important allies in efforts to acquire large contiguous tracts of hunting land.
DA - 2015/3/4/
PY - 2015/3/4/
DO - 10.1080/10871209.2014.997328
VL - 20
IS - 2
SP - 174-181
J2 - Human Dimensions of Wildlife
LA - en
OP -
SN - 1087-1209 1533-158X
UR - http://dx.doi.org/10.1080/10871209.2014.997328
DB - Crossref
KW - deer hunting
KW - dog hunting
KW - hunting
KW - hunting tradition
KW - North Carolina
ER -
TY - JOUR
TI - Stormwater control measure (SCM) maintenance considerations to ensure designed functionality
AU - Blecken, Godecke-Tobias
AU - Hunt, William F., III
AU - Al-Rubaei, Ahmed Mohammed
AU - Viklander, Maria
AU - Lord, William G.
T2 - Urban Water Journal
AB - Great investment is made in the design and installation of stormwater control measures (SCMs). Substantial research investment, too, is made to optimise the performance of SCMs. However, once installed, SCMs often suffer from lack of maintenance or even outright neglect. Key maintenance needs for wet ponds, constructed stormwater wetlands, bioretention, infiltration practices, permeable pavement, swales, and rainwater harvesting systems are reviewed with many tasks, such as the cleaning of pre-treatment areas and the preservation of infiltration surfaces, being common maintenance themes among SCMs. Consequences of lacking maintenance are illustrated (mainly insufficient function or failure). Probable reasons for neglect include insufficient communication, unclear responsibilities, lack of knowledge, financial barriers, and decentralised measures. In future designs and research, maintenance (and lack thereof) should be considered. Assessing the performance of SCMs conservatively and including safety factors may prevent consequences of under-maintenance; and requiring regular inspection may help to enforce sufficient maintenance.
DA - 2015/11/26/
PY - 2015/11/26/
DO - 10.1080/1573062X.2015.1111913
VL - 14
IS - 3
SP - 278-290
J2 - Urban Water Journal
LA - en
OP -
SN - 1573-062X 1744-9006
UR - http://dx.doi.org/10.1080/1573062X.2015.1111913
DB - Crossref
KW - Stormwater
KW - maintenance
KW - inspection
KW - LID
KW - WSUD
KW - asset management
KW - SCMs
KW - long-term function
ER -
TY - JOUR
TI - Prediction of human population responses to toxic compounds by a collaborative competition
AU - Eduati, Federica
AU - Mangravite, Lara M
AU - Wang, Tao
AU - Tang, Hao
AU - Bare, J Christopher
AU - Huang, Ruili
AU - Norman, Thea
AU - Kellen, Mike
AU - Menden, Michael P
AU - Yang, Jichen
AU - Zhan, Xiaowei
AU - Zhong, Rui
AU - Xiao, Guanghua
AU - Xia, Menghang
AU - Abdo, Nour
AU - Kosyk, Oksana
AU - Friend, Stephen
AU - Dearry, Allen
AU - Simeonov, Anton
AU - Tice, Raymond R
AU - Rusyn, Ivan
AU - Wright, Fred A
AU - Stolovitzky, Gustavo
AU - Xie, Yang
AU - Saez-Rodriguez, Julio
T2 - Nature Biotechnology
AB - The ability to computationally predict the effects of toxic compounds on humans could help address the deficiencies of current chemical safety testing. Here, we report the results from a community-based DREAM challenge to predict toxicities of environmental compounds with potential adverse health effects for human populations. We measured the cytotoxicity of 156 compounds in 884 lymphoblastoid cell lines for which genotype and transcriptional data are available as part of the Tox21 1000 Genomes Project. The challenge participants developed algorithms to predict interindividual variability of toxic response from genomic profiles and population-level cytotoxicity data from structural attributes of the compounds. 179 submitted predictions were evaluated against an experimental data set to which participants were blinded. Individual cytotoxicity predictions were better than random, with modest correlations (Pearson's r < 0.28), consistent with complex trait genomic prediction. In contrast, predictions of population-level response to different compounds were higher (r < 0.66). The results highlight the possibility of predicting health risks associated with unknown compounds, although risk estimation accuracy remains suboptimal.
DA - 2015/8/10/
PY - 2015/8/10/
DO - 10.1038/NBT.3299
VL - 33
IS - 9
SP - 933-940
J2 - Nat Biotechnol
LA - en
OP -
SN - 1087-0156 1546-1696
UR - http://dx.doi.org/10.1038/NBT.3299
DB - Crossref
ER -
TY - JOUR
TI - Erratum: Prediction of human population responses to toxic compounds by a collaborative competition
AU - Eduati, Federica
AU - Mangravite, Lara M
AU - Wang, Tao
AU - Tang, Hao
AU - Bare, J Christopher
AU - Huang, Ruili
AU - Norman, Thea
AU - Kellen, Mike
AU - Menden, Michael P
AU - Yang, Jichen
AU - Zhan, Xiaowei
AU - Zhong, Rui
AU - Xiao, Guanghua
AU - Xia, Menghang
AU - Abdo, Nour
AU - Kosyk, Oksana
AU - NIEHS-NCATS-UNC DREAM Toxicogenetic, the
AU - Friend, Stephen
AU - Dearry, Allen
AU - Simeonov, Anton
AU - Tice, Raymond R
AU - Rusyn, Ivan
AU - Wright, Fred A
AU - Stolovitzky, Gustavo
AU - Xie, Yang
AU - Saez-Rodriguez, Julio
T2 - Nature Biotechnology
AB - Nat. Biotechnol. 33, 933–940 (2015); published online 10 August 2015; corrected after print 1 October 2015 In the version of this article initially published, in the HTML only, all authors names were incorrectly included in the main author list, and several authors names were repeated. The authors have now added 12 additional authors to the list of “Other participants in the NIEHS-NCATS-UNC DREAM Toxicogenetics Collaboration,” including Alok Jaiswal, Antti Poso, Himanshu Chheda, Ismeet Kaur, Jing Tang, John-Patrick Mpindi, Krister Wennerberg, Natalio Krasnogor, Samuel Kaski, Tero Aittokallio, Petteri Hintsanen and Suleiman Ali Khan.
DA - 2015/10//
PY - 2015/10//
DO - 10.1038/NBT1015-1109A
VL - 33
IS - 10
SP - 1109-1109
J2 - Nat Biotechnol
LA - en
OP -
SN - 1087-0156 1546-1696
UR - http://dx.doi.org/10.1038/NBT1015-1109A
DB - Crossref
ER -
TY - JOUR
TI - Pharmacometabolomic Assessments of Atenolol and Hydrochlorothiazide Treatment Reveal Novel Drug Response Phenotypes
AU - Rotroff, DM
AU - Shahin, MH
AU - Gurley, SB
AU - Zhu, H
AU - Motsinger-Reif, A
AU - Meisner, M
AU - Beitelshees, AL
AU - Fiehn, O
AU - Johnson, JA
AU - Elbadawi-Sidhu, M
AU - Frye, RF
AU - Gong, Y
AU - Weng, L
AU - Cooper-DeHoff, RM
AU - Kaddurah-Daouk, R
T2 - CPT: Pharmacometrics & Systems Pharmacology
AB - Achieving hypertension (HTN) control and mitigating the adverse health effects associated with HTN continues to be a global challenge. Some individuals respond poorly to current HTN therapies, and mechanisms for response variation remain poorly understood. We used a nontargeted metabolomics approach (gas chromatography time-of-flight/mass spectrometry gas chromatography time-of-flight/mass spectrometry) measuring 489 metabolites to characterize metabolite signatures associated with treatment response to anti-HTN drugs, atenolol (ATEN), and hydrochlorothiazide (HCTZ), in white and black participants with uncomplicated HTN enrolled in the Pharmacogenomic Evaluation of Antihypertensive Responses study. Metabolite profiles were significantly different between races, and metabolite responses associated with home diastolic blood pressure (HDBP) response were identified. Metabolite pathway analyses identified gluconeogenesis, plasmalogen synthesis, and tryptophan metabolism increases in white participants treated with HCTZ (P < 0.05). Furthermore, we developed predictive models from metabolite signatures of HDBP treatment response (P < 1 × 10−5). As part of a quantitative systems pharmacology approach, the metabolites identified herein may serve as biomarkers for improving treatment decisions and elucidating mechanisms driving HTN treatment responses.
DA - 2015/10/29/
PY - 2015/10/29/
DO - 10.1002/PSP4.12017
VL - 4
IS - 11
SP - 669-679
J2 - CPT Pharmacometrics Syst. Pharmacol.
LA - en
OP -
SN - 2163-8306
UR - http://dx.doi.org/10.1002/PSP4.12017
DB - Crossref
ER -
TY - JOUR
TI - Joint Analysis of Psychiatric Disorders Increases Accuracy of Risk Prediction for Schizophrenia, Bipolar Disorder, and Major Depressive Disorder
AU - Maier, Robert
AU - Moser, Gerhard
AU - Chen, Guo-Bo
AU - Ripke, Stephan
AU - Coryell, William
AU - Potash, James B.
AU - Scheftner, William A.
AU - Shi, Jianxin
AU - Weissman, Myrna M.
AU - Hultman, Christina M.
AU - Landén, Mikael
AU - Levinson, Douglas F.
AU - Kendler, Kenneth S.
AU - Smoller, Jordan W.
AU - Wray, Naomi R.
AU - Lee, S. Hong
AU - Absher, Devin
AU - Agartz, Ingrid
AU - Akil, Huda
AU - Amin, Farooq
AU - Andreassen, Ole A.
AU - Anjorin, Adebayo
AU - Anney, Richard
AU - Arking, Dan E.
AU - Asherson, Philip
AU - Azevedo, Maria H.
AU - Backlund, Lena
AU - Badner, Judith A.
AU - Bailey, Anthony J.
AU - Banaschewski, Tobias
AU - Barchas, Jack D.
AU - Barnes, Michael R.
AU - Barrett, Thomas B.
AU - Bass, Nicholas
AU - Battaglia, Agatino
AU - Bauer, Michael
AU - Bayés, Mònica
AU - Bellivier, Frank
AU - Bergen, Sarah E.
AU - Berrettini, Wade
AU - Betancur, Catalina
AU - Bettecken, Thomas
AU - Biederman, Joseph
AU - Binder, Elisabeth B.
AU - Black, Donald W.
AU - Blackwood, Douglas H.R.
AU - Bloss, Cinnamon S.
AU - Boehnke, Michael
AU - Boomsma, Dorret I.
AU - Breen, Gerome
AU - Breuer, René
AU - Bruggeman, Richard
AU - Buccola, Nancy G.
AU - Buitelaar, Jan K.
AU - Bunney, William E.
AU - Buxbaum, Joseph D.
AU - Byerley, William F.
AU - Caesar, Sian
AU - Cahn, Wiepke
AU - Cantor, Rita M.
AU - Casas, Miguel
AU - Chakravarti, Aravinda
AU - Chambert, Kimberly
AU - Choudhury, Khalid
AU - Cichon, Sven
AU - Cloninger, C. Robert
AU - Collier, David A.
AU - Cook, Edwin H.
AU - Coon, Hilary
AU - Cormand, Bru
AU - Cormican, Paul
AU - Corvin, Aiden
AU - Coryell, William H.
AU - Craddock, Nicholas
AU - Craig, David W.
AU - Craig, Ian W.
AU - Crosbie, Jennifer
AU - Cuccaro, Michael L.
AU - Curtis, David
AU - Czamara, Darina
AU - Daly, Mark J.
AU - Datta, Susmita
AU - Dawson, Geraldine
AU - Day, Richard
AU - De Geus, Eco J.
AU - Degenhardt, Franziska
AU - Devlin, Bernie
AU - Djurovic, Srdjan
AU - Donohoe, Gary J.
AU - Doyle, Alysa E.
AU - Duan, Jubao
AU - Dudbridge, Frank
AU - Duketis, Eftichia
AU - Ebstein, Richard P.
AU - Edenberg, Howard J.
AU - Elia, Josephine
AU - Ennis, Sean
AU - Etain, Bruno
AU - Fanous, Ayman
AU - Faraone, Stephen V.
AU - Farmer, Anne E.
AU - Ferrier, I. Nicol
AU - Flickinger, Matthew
AU - Fombonne, Eric
AU - Foroud, Tatiana
AU - Frank, Josef
AU - Franke, Barbara
AU - Fraser, Christine
AU - Freedman, Robert
AU - Freimer, Nelson B.
AU - Freitag, Christine M.
AU - Friedl, Marion
AU - Frisén, Louise
AU - Gallagher, Louise
AU - Gejman, Pablo V.
AU - Georgieva, Lyudmila
AU - Gershon, Elliot S.
AU - Geschwind, Daniel H.
AU - Giegling, Ina
AU - Gill, Michael
AU - Gordon, Scott D.
AU - Gordon-Smith, Katherine
AU - Green, Elaine K.
AU - Greenwood, Tiffany A.
AU - Grice, Dorothy E.
AU - Gross, Magdalena
AU - Grozeva, Detelina
AU - Guan, Weihua
AU - Gurling, Hugh
AU - De Haan, Lieuwe
AU - Haines, Jonathan L.
AU - Hakonarson, Hakon
AU - Hallmayer, Joachim
AU - Hamilton, Steven P.
AU - Hamshere, Marian L.
AU - Hansen, Thomas F.
AU - Hartmann, Annette M.
AU - Hautzinger, Martin
AU - Heath, Andrew C.
AU - Henders, Anjali K.
AU - Herms, Stefan
AU - Hickie, Ian B.
AU - Hipolito, Maria
AU - Hoefels, Susanne
AU - Holmans, Peter A.
AU - Holsboer, Florian
AU - Hoogendijk, Witte J.
AU - Hottenga, Jouke-Jan
AU - Hultman, Christina M.
AU - Hus, Vanessa
AU - Ingason, Andrés
AU - Ising, Marcus
AU - Jamain, Stéphane
AU - Jones, Ian
AU - Jones, Lisa
AU - Kähler, Anna K.
AU - Kahn, René S.
AU - Kandaswamy, Radhika
AU - Keller, Matthew C.
AU - Kelsoe, John R.
AU - Kendler, Kenneth S.
AU - Kennedy, James L.
AU - Kenny, Elaine
AU - Kent, Lindsey
AU - Kim, Yunjung
AU - Kirov, George K.
AU - Klauck, Sabine M.
AU - Klei, Lambertus
AU - Knowles, James A.
AU - Kohli, Martin A.
AU - Koller, Daniel L.
AU - Konte, Bettina
AU - Korszun, Ania
AU - Krabbendam, Lydia
AU - Krasucki, Robert
AU - Kuntsi, Jonna
AU - Kwan, Phoenix
AU - Landén, Mikael
AU - Långström, Niklas
AU - Lathrop, Mark
AU - Lawrence, Jacob
AU - Lawson, William B.
AU - Leboyer, Marion
AU - Ledbetter, David H.
AU - Lee, Phil H.
AU - Lencz, Todd
AU - Lesch, Klaus-Peter
AU - Levinson, Douglas F.
AU - Lewis, Cathryn M.
AU - Li, Jun
AU - Lichtenstein, Paul
AU - Lieberman, Jeffrey A.
AU - Lin, Dan-Yu
AU - Linszen, Don H.
AU - Liu, Chunyu
AU - Lohoff, Falk W.
AU - Loo, Sandra K.
AU - Lord, Catherine
AU - Lowe, Jennifer K.
AU - Lucae, Susanne
AU - MacIntyre, Donald J.
AU - Madden, Pamela A.F.
AU - Maestrini, Elena
AU - Magnusson, Patrik K.E.
AU - Mahon, Pamela B.
AU - Maier, Wolfgang
AU - Malhotra, Anil K.
AU - Mane, Shrikant M.
AU - Martin, Christa L.
AU - Martin, Nicholas G.
AU - Mattheisen, Manuel
AU - Matthews, Keith
AU - Mattingsdal, Morten
AU - McCarroll, Steven A.
AU - McGhee, Kevin A.
AU - McGough, James J.
AU - McGrath, Patrick J.
AU - McGuffin, Peter
AU - McInnis, Melvin G.
AU - McIntosh, Andrew
AU - McKinney, Rebecca
AU - McLean, Alan W.
AU - McMahon, Francis J.
AU - McMahon, William M.
AU - McQuillin, Andrew
AU - Medeiros, Helena
AU - Medland, Sarah E.
AU - Meier, Sandra
AU - Melle, Ingrid
AU - Meng, Fan
AU - Meyer, Jobst
AU - Middeldorp, Christel M.
AU - Middleton, Lefkos
AU - Milanova, Vihra
AU - Miranda, Ana
AU - Monaco, Anthony P.
AU - Montgomery, Grant W.
AU - Moran, Jennifer L.
AU - Moreno-De-Luca, Daniel
AU - Morken, Gunnar
AU - Morris, Derek W.
AU - Morrow, Eric M.
AU - Moskvina, Valentina
AU - Mowry, Bryan J.
AU - Muglia, Pierandrea
AU - Mühleisen, Thomas W.
AU - Müller-Myhsok, Bertram
AU - Murtha, Michael
AU - Myers, Richard M.
AU - Myin-Germeys, Inez
AU - Neale, Benjamin M.
AU - Nelson, Stan F.
AU - Nievergelt, Caroline M.
AU - Nikolov, Ivan
AU - Nimgaonkar, Vishwajit
AU - Nolen, Willem A.
AU - Nöthen, Markus M.
AU - Nurnberger, John I.
AU - Nwulia, Evaristus A.
AU - Nyholt, Dale R.
AU - O’Donovan, Michael C.
AU - O’Dushlaine, Colm
AU - Oades, Robert D.
AU - Olincy, Ann
AU - Oliveira, Guiomar
AU - Olsen, Line
AU - Ophoff, Roel A.
AU - Osby, Urban
AU - Owen, Michael J.
AU - Palotie, Aarno
AU - Parr, Jeremy R.
AU - Paterson, Andrew D.
AU - Pato, Carlos N.
AU - Pato, Michele T.
AU - Penninx, Brenda W.
AU - Pergadia, Michele L.
AU - Pericak-Vance, Margaret A.
AU - Perlis, Roy H.
AU - Pickard, Benjamin S.
AU - Pimm, Jonathan
AU - Piven, Joseph
AU - Posthuma, Danielle
AU - Potash, James B.
AU - Poustka, Fritz
AU - Propping, Peter
AU - Purcell, Shaun M.
AU - Puri, Vinay
AU - Quested, Digby J.
AU - Quinn, Emma M.
AU - Ramos-Quiroga, Josep Antoni
AU - Rasmussen, Henrik B.
AU - Raychaudhuri, Soumya
AU - Rehnström, Karola
AU - Reif, Andreas
AU - Ribasés, Marta
AU - Rice, John P.
AU - Rietschel, Marcella
AU - Ripke, Stephan
AU - Roeder, Kathryn
AU - Roeyers, Herbert
AU - Rossin, Lizzy
AU - Rothenberger, Aribert
AU - Rouleau, Guy
AU - Ruderfer, Douglas
AU - Rujescu, Dan
AU - Sanders, Alan R.
AU - Sanders, Stephan J.
AU - Santangelo, Susan L.
AU - Schachar, Russell
AU - Schalling, Martin
AU - Schatzberg, Alan F.
AU - Scheftner, William A.
AU - Schellenberg, Gerard D.
AU - Scherer, Stephen W.
AU - Schork, Nicholas J.
AU - Schulze, Thomas G.
AU - Schumacher, Johannes
AU - Schwarz, Markus
AU - Scolnick, Edward
AU - Scott, Laura J.
AU - Sergeant, Joseph A.
AU - Shi, Jianxin
AU - Shilling, Paul D.
AU - Shyn, Stanley I.
AU - Silverman, Jeremy M.
AU - Sklar, Pamela
AU - Slager, Susan L.
AU - Smalley, Susan L.
AU - Smit, Johannes H.
AU - Smith, Erin N.
AU - Smoller, Jordan W.
AU - Sonuga-Barke, Edmund J.S.
AU - St Clair, David
AU - State, Matthew
AU - Steffens, Michael
AU - Steinhausen, Hans-Christoph
AU - Strauss, John S.
AU - Strohmaier, Jana
AU - Stroup, T. Scott
AU - Sullivan, Patrick F.
AU - Sutcliffe, James
AU - Szatmari, Peter
AU - Szelinger, Szabocls
AU - Thapar, Anita
AU - Thirumalai, Srinivasa
AU - Thompson, Robert C.
AU - Todorov, Alexandre A.
AU - Tozzi, Federica
AU - Treutlein, Jens
AU - Tzeng, Jung-Ying
AU - Uhr, Manfred
AU - van den Oord, Edwin J.C.G.
AU - Van Grootheest, Gerard
AU - Van Os, Jim
AU - Vicente, Astrid M.
AU - Vieland, Veronica J.
AU - Vincent, John B.
AU - Visscher, Peter M.
AU - Walsh, Christopher A.
AU - Wassink, Thomas H.
AU - Watson, Stanley J.
AU - Weiss, Lauren A.
AU - Weissman, Myrna M.
AU - Werge, Thomas
AU - Wienker, Thomas F.
AU - Wiersma, Durk
AU - Wijsman, Ellen M.
AU - Willemsen, Gonneke
AU - Williams, Nigel
AU - Willsey, A. Jeremy
AU - Witt, Stephanie H.
AU - Wray, Naomi R.
AU - Xu, Wei
AU - Young, Allan H.
AU - Yu, Timothy W.
AU - Zammit, Stanley
AU - Zandi, Peter P.
AU - Zhang, Peng
AU - Zitman, Frans G.
AU - Zöllner, Sebastian
T2 - The American Journal of Human Genetics
AB - Genetic risk prediction has several potential applications in medical research and clinical practice and could be used, for example, to stratify a heterogeneous population of patients by their predicted genetic risk. However, for polygenic traits, such as psychiatric disorders, the accuracy of risk prediction is low. Here we use a multivariate linear mixed model and apply multi-trait genomic best linear unbiased prediction for genetic risk prediction. This method exploits correlations between disorders and simultaneously evaluates individual risk for each disorder. We show that the multivariate approach significantly increases the prediction accuracy for schizophrenia, bipolar disorder, and major depressive disorder in the discovery as well as in independent validation datasets. By grouping SNPs based on genome annotation and fitting multiple random effects, we show that the prediction accuracy could be further improved. The gain in prediction accuracy of the multivariate approach is equivalent to an increase in sample size of 34% for schizophrenia, 68% for bipolar disorder, and 76% for major depressive disorders using single trait models. Because our approach can be readily applied to any number of GWAS datasets of correlated traits, it is a flexible and powerful tool to maximize prediction accuracy. With current sample size, risk predictors are not useful in a clinical setting but already are a valuable research tool, for example in experimental designs comparing cases with high and low polygenic risk.
DA - 2015/2//
PY - 2015/2//
DO - 10.1016/J.AJHG.2014.12.006
VL - 96
IS - 2
SP - 283-294
J2 - The American Journal of Human Genetics
LA - en
OP -
SN - 0002-9297
UR - http://dx.doi.org/10.1016/J.AJHG.2014.12.006
DB - Crossref
ER -
TY - JOUR
TI - Selective Internal Radiation Therapy: Quantifying Distal Penetration and Distribution of Resin and Glass Microspheres in a Surrogate Arterial Model
AU - Jernigan, Shaphan R.
AU - Osborne, Jason A.
AU - Mirek, Christopher J.
AU - Buckner, Gregory
T2 - Journal of Vascular and Interventional Radiology
AB - To experimentally investigate the effects of microsphere density and diameter on distal penetration.A surrogate hepatic arterial system was developed to replicate the hemodynamics (pressures, flow rates, pulsatile flow characteristics) and anatomic geometry (vessel diameters) proximal and distal to the microsphere injection point. A planar tumor model, placed distal to the injection point, allowed visualization of deposited microspheres. Bland resin and glass microspheres, with physical characteristics approximating the characteristics of commercially available products, were injected into the surrogate system. Microsphere type, injection rate, systemic flow rate, and tumor model inclination were varied among tests (glass, n = 7; resin, n = 6) with replicates for 2 conditions. After injection, 254 micrographs were obtained at previously defined locations throughout the tumor model to document microsphere distributions. Average microsphere distributions and mass measurements of microspheres collected at the tumor outlet were analyzed to quantify distal penetration for each case.Across all test conditions, average penetration depths of resin microspheres were higher compared with glass microspheres (45.1 cm ± 11.8 vs 22.3 cm ± 9.9). The analysis of variance indicated that the observed difference between microsphere type (glass vs resin) was significant (P = .005, df = 1,2). The observed distance means did not differ significantly across flow rate or inclination angle.Penetration depths of resin microspheres were significantly higher than penetration depths of glass microspheres in the surrogate hepatic arterial system.
DA - 2015/6//
PY - 2015/6//
DO - 10.1016/J.JVIR.2015.02.022
VL - 26
IS - 6
SP - 897-904.e2
J2 - Journal of Vascular and Interventional Radiology
LA - en
OP -
SN - 1051-0443
UR - http://dx.doi.org/10.1016/J.JVIR.2015.02.022
DB - Crossref
ER -
TY - JOUR
TI - Influence of Drawdown Period on Overflow Volume and Pollutant Treatment for Detention-Based Stormwater Control Measures in Raleigh, North Carolina
AU - Smolek, Alessandra P.
AU - Hunt, William F., III
AU - Grabow, Garry L.
T2 - Journal of Sustainable Water in the Built Environment
AB - The drawdown rate of detention-based stormwater control measures (SCMs) influences both the treatment capability of the device and the volume of runoff that becomes untreated overflow. Currently, hydrologic design goals set by the North Carolina Department of Environmental and Natural Resources and other mid-Atlantic U.S. state agencies (e.g., those in Maryland, Virginia, and Pennsylvania) require stormwater practices to treat, e.g., 90% of stormwater runoff (or similar). This equates to a 10% overflow volume, defined as the percentage of inflow volume that bypasses the SCM and therefore receives minimal treatment. For detention-based SCMs, this design goal is met by sizing the outlet to release runoff generated from the water quality event (in North Carolina, either 25 or 38 mm) over a required minimum period of 2 days. Previous studies have not shown whether rainfall patterns in North Carolina and other east coast United States states justify a 2-day drawdown rate of the water quality event to limit the annual average overflow volume to 10%. To investigate this, rainfall patterns in Raleigh, North Carolina, were evaluated from Years 2001 to 2010 to determine the fraction of untreated overflow that would result from various design configurations and their associated drawdown periods. Overflow volumes were calculated on an hourly basis by a simple model routing stormwater runoff through a theoretical constructed stormwater wetland (CSW) sized to release the water quality event over drawdown periods of 12 and 18 h, 1 day, 36 h, and 2–5 days. A 2-day drawdown period resulted in an annual average overflow volume of 11.7%, exceeding the design goal of 10%, although not significantly (p=0.1702). A more simplistic approach quantifying overflow volume based on rainfall data determined that 20.1% of rainfall depths are associated with storm events in the Raleigh–Durham area exceeding 25 mm. Both methods suggest that for the Raleigh–Durham area, if a 2-day drawdown is used for the 25-mm water quality event, less than 90% of stormwater runoff will be treated. To ensure that 90% of all runoff received some treatment, the 25-mm water quality event drawdown time would need to be reduced to 36 h. Any reduction in drawdown time, while creating storage space in the SCM for subsequent events, necessarily reduces treatment efficiency by decreasing time for sedimentation and other biogeochemical nutrient removal processes to occur. If a 15% average overflow volume was acceptable, analyses indicate that drawdown periods up to 3 days could be used. Lengthening the drawdown period to 3 days enables more treatment of captured runoff and in a CSW could yield an additional 3–5% nitrogen and phosphorus load reduction, despite the slightly higher bypass volume.
DA - 2015/5//
PY - 2015/5//
DO - 10.1061/JSWBAY.0000798
VL - 1
IS - 2
SP - 05015001
J2 - J. Sustainable Water Built Environ.
LA - en
OP -
SN - 2379-6111 2379-6111
UR - http://dx.doi.org/10.1061/JSWBAY.0000798
DB - Crossref
KW - Hydraulic retention time
KW - Stormwater wetlands
KW - Overflow volume
KW - North Carolina
ER -
TY - JOUR
TI - Comparison of Runoff Quality and Quantity from a Commercial Low-Impact and Conventional Development in Raleigh, North Carolina
AU - Wilson, C. E.
AU - Hunt, W. F.
AU - Winston, R. J.
AU - Smith, P.
T2 - Journal of Environmental Engineering
AB - Urbanization and its associated increased impervious footprint lead to stream impairment through erosion, flooding, and augmented pollutant loads. Low-impact development (LID) focuses on disconnecting impervious areas, increasing infiltration and evapotranspiration, and treating storm water on site through the use of storm water control measures (SCMs). In this study, a conventional development (centralized storm-water management) and an adjoining infiltration-based LID commercial site in Raleigh, North Carolina, were compared with respect to hydrology and water quality. The conventional development [2.76 ha, 61% directly connected impervious area (DCIA)] and the LID (2.53 ha, 84% DCIA) had underlying hydrologic soil group B soils. The LID was treated by a mix of green (aboveground) and grey (underground) infrastructure including an underground detention chamber and infiltration gallery, underground and aboveground cisterns, and aboveground swales and bioretention; the conventional development was treated with a dry detention basin and swales. Inflow and outflow runoff volumes and peak flows were normalized by DCIA. For the 47 hydrologic storms monitored, runoff coefficients of 0.02 at the LID site and 0.49 at the conventional site were recorded. The conventional development had an 11-fold higher median peak flow rate than the LID site. For the three storms more intense than the 10-year, 5-min average recurrence interval (ARI) event, the conventional site Qp was an average of 7.7 times higher than that of the LID. Flow proportional, composite water-quality samples were analyzed for total nitrogen (TN), total phosphorus (TP), total Kjeldahl nitrogen (TKN), total ammoniacal nitrogen (TAN), nitrite-nitrate nitrogen (NOX), organic nitrogen (ON), orthophosphate (Ortho-P), and total suspended solids (TSS). Generally, no significant difference in pollutant event mean concentrations (EMCs) was observed between sites. For the 20 water-quality storms sampled, the LID site produced pollutant loadings that were less than 5% of those at the conventional site for all species studied. Results demonstrated highly effective and space-saving solutions when green and grey infrastructure are merged, which is often the case when constructing on high land-cost properties. The exceptional results from this LID were due to (1) an overdesigned system capable of capturing the 77-mm storm, rather than a typical 25-mm storm, and (2) the high infiltration capacity of the type B soils coupled with a high driving head (∼3 m).
DA - 2015/2//
PY - 2015/2//
DO - 10.1061/(ASCE)EE.1943-7870.0000842
VL - 141
IS - 2
SP - 05014005
J2 - J. Environ. Eng.
LA - en
OP -
SN - 0733-9372 1943-7870
UR - http://dx.doi.org/10.1061/(ASCE)EE.1943-7870.0000842
DB - Crossref
KW - Low impact development
KW - Green infrastructure
KW - Grey infrastructure
KW - Stormwater management
KW - Runoff
KW - Nutrients
KW - Infiltration
KW - North Carolina
KW - Hydrology
KW - Peak flow
ER -
TY - JOUR
TI - Perspectives of wildlife conservation professionals on intensive deer management
AU - Chitwood, M. Colter
AU - Peterson, M. Nils
AU - Bondell, Howard D.
AU - Lashley, Marcus A.
AU - Brown, Robert D.
AU - Deperno, Christopher S.
T2 - Wildlife Society Bulletin
AB - Intensive deer management (IDM) is fundamentally changing how one of the most important game species in North America is being managed, but little is known about how wildlife conservation professionals view these changes. The IDM approach encourages privatization of deer (Odocoileus spp.) through practices including feeding, high fencing, artificial insemination and markets in deer semen, and translocation. To evaluate support for IDM practices, we surveyed 208 registrants of the 2010 Southeast Deer Study Group Meeting held in San Antonio, Texas, USA. Specifically, we evaluated support for IDM practices using state-agency wildlife biologists, private wildlife managers, and academics, and we evaluated how geographic region and employment type are related to opinions about IDM. Using Principal Components Analysis, we created 3 new scales that measured respondents’ opinions about deer management, deer husbandry, and deer hunting. We detected strong opposition to IDM among respondents, with respondents from universities having the strongest opposition, followed by state-agency employees from Texas, and private consultants from Texas (the latter having the greatest support for IDM). Our study highlights the need for critical and empirical evaluation of the articulation between IDM and the North American Model of Wildlife Conservation, particularly the tenets that assert wildlife are held in the public trust and advocate elimination of markets for wildlife. © 2015 The Wildlife Society.
DA - 2015/11/26/
PY - 2015/11/26/
DO - 10.1002/WSB.607
VL - 39
IS - 4
SP - 751-756
J2 - Wildl. Soc. Bull.
LA - en
OP -
SN - 1938-5463
UR - http://dx.doi.org/10.1002/WSB.607
DB - Crossref
KW - deer management
KW - North American Model
KW - Odocoileus virginianus
KW - privatization
KW - Texas
KW - white-tailed deer
ER -
TY - CHAP
TI - Quantitative SNP Genotyping of Polyploids with MassARRAY and Other Platforms
AU - Mollinari, M.
AU - Serang, O.
T2 - Methods in Molecular Biology
AB - Accurate genotyping is essential for building genetic maps and performing genome assembly of polyploid species. Recent high-throughput techniques, such as Illumina GoldenGate™ and Sequenom iPLEX MassARRAY®, have made it possible to accurately estimate the relative abundances of different alleles even when the ploidy of the population is unknown. Here we describe the experimental methods for collecting these relative allele intensities and then demonstrate the practical concerns for inferring genotypes using Bayesian inference via the software package SuperMASSA.
PY - 2015///
DO - 10.1007/978-1-4939-1966-6_17
VL - 1245
SP - 215-241
UR - http://dx.doi.org/10.1007/978-1-4939-1966-6_17
KW - Polyploids
KW - MassARRAY
KW - SNP
KW - Quantitative genotyping
ER -
TY - JOUR
TI - Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis
AU - Corvol, Harriet
AU - Blackman, Scott M.
AU - Boëlle, Pierre-Yves
AU - Gallins, Paul J.
AU - Pace, Rhonda G.
AU - Stonebraker, Jaclyn R.
AU - Accurso, Frank J.
AU - Clement, Annick
AU - Collaco, Joseph M.
AU - Dang, Hong
AU - Dang, Anthony T.
AU - Franca, Arianna
AU - Gong, Jiafen
AU - Guillot, Loic
AU - Keenan, Katherine
AU - Li, Weili
AU - Lin, Fan
AU - Patrone, Michael V.
AU - Raraigh, Karen S.
AU - Sun, Lei
AU - Zhou, Yi-Hui
AU - O’Neal, Wanda K.
AU - Sontag, Marci K.
AU - Levy, Hara
AU - Durie, Peter R.
AU - Rommens, Johanna M.
AU - Drumm, Mitchell L.
AU - Wright, Fred A.
AU - Strug, Lisa J.
AU - Cutting, Garry R.
AU - Knowles, Michael R.
T2 - Nature Communications
AB - The identification of small molecules that target specific CFTR variants has ushered in a new era of treatment for cystic fibrosis (CF), yet optimal, individualized treatment of CF will require identification and targeting of disease modifiers. Here we use genome-wide association analysis to identify genetic modifiers of CF lung disease, the primary cause of mortality. Meta-analysis of 6,365 CF patients identifies five loci that display significant association with variation in lung disease. Regions on chr3q29 (MUC4/MUC20; P=3.3 × 10(-11)), chr5p15.3 (SLC9A3; P=6.8 × 10(-12)), chr6p21.3 (HLA Class II; P=1.2 × 10(-8)) and chrXq22-q23 (AGTR2/SLC6A14; P=1.8 × 10(-9)) contain genes of high biological relevance to CF pathophysiology. The fifth locus, on chr11p12-p13 (EHF/APIP; P=1.9 × 10(-10)), was previously shown to be associated with lung disease. These results provide new insights into potential targets for modulating lung disease severity in CF.
DA - 2015/9/29/
PY - 2015/9/29/
DO - 10.1038/NCOMMS9382
VL - 6
IS - 1
J2 - Nat Commun
LA - en
OP -
SN - 2041-1723
UR - http://dx.doi.org/10.1038/NCOMMS9382
DB - Crossref
ER -
TY - JOUR
TI - Identification of Novel Gene Targets and Putative Regulators of Arsenic-Associated DNA Methylation in Human Urothelial Cells and Bladder Cancer
AU - Rager, Julia E.
AU - Tilley, Sloane K.
AU - Tulenko, Samantha E.
AU - Smeester, Lisa
AU - Ray, Paul D.
AU - Yosim, Andrew
AU - Currier, Jenna M.
AU - Ishida, María C.
AU - González-Horta, Maria del Carmen
AU - Sánchez-Ramírez, Blanca
AU - Ballinas-Casarrubias, Lourdes
AU - Gutiérrez-Torres, Daniela S.
AU - Drobná, Zuzana
AU - Del Razo, Luz M.
AU - García-Vargas, Gonzalo G.
AU - Kim, William Y.
AU - Zhou, Yi-Hui
AU - Wright, Fred A.
AU - Stýblo, Miroslav
AU - Fry, Rebecca C.
T2 - Chemical Research in Toxicology
AB - There is strong epidemiologic evidence linking chronic exposure to inorganic arsenic (iAs) to myriad adverse health effects, including cancer of the bladder. We set out to identify DNA methylation patterns associated with arsenic and its metabolites in exfoliated urothelial cells (EUCs) that originate primarily from the urinary bladder, one of the targets of arsenic-induced carcinogenesis. Genome-wide, gene-specific promoter DNA methylation levels were assessed in EUCs from 46 residents of Chihuahua, Mexico, and the relationship was examined between promoter methylation profiles and the intracellular concentrations of total arsenic and arsenic species. A set of 49 differentially methylated genes was identified with increased promoter methylation associated with EUC tAs, iAs, and/or monomethylated As (MMAs) enriched for their roles in metabolic disease and cancer. Notably, no genes had differential methylation associated with EUC dimethylated As (DMAs), suggesting that DMAs may influence DNA methylation-mediated urothelial cell responses to a lesser extent than iAs or MMAs. Further analysis showed that 22 of the 49 arsenic-associated genes (45%) are also differentially methylated in bladder cancer tissue identified using The Cancer Genome Atlas repository. Both the arsenic- and cancer-associated genes are enriched for the binding sites of common transcription factors known to play roles in carcinogenesis, demonstrating a novel potential mechanistic link between iAs exposure and bladder cancer.
DA - 2015/6/3/
PY - 2015/6/3/
DO - 10.1021/TX500393Y
VL - 28
IS - 6
SP - 1144-1155
J2 - Chem. Res. Toxicol.
LA - en
OP -
SN - 0893-228X 1520-5010
UR - http://dx.doi.org/10.1021/TX500393Y
DB - Crossref
ER -
TY - JOUR
TI - A robust method for estimating optimal treatment regimes
AU - Zhang, B.
AU - Tsiatis, A.A.
AU - Laber, E.B.
AU - Davidian, M.
T2 - Biometrics
AB - BiometricsVolume 71, Issue 1 p. 267-273 READER REACTIONFree Access Response to reader reaction First published: 29 October 2014 https://doi.org/10.1111/biom.12229AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat The authors replied as follows: We applaud Taylor, Cheng, and Foster (henceforth TCF) for carrying out additional empirical studies of methods for estimating optimal treatment regimes, as further elucidation of the relative performance of competing methods is sorely needed. We hope that the evidence suggesting that these methods can perform well and yield comparable results under conditions likely to hold in practice will encourage more widespread interest in estimation of optimal treatment regimes. TCF consider the situation where the class of regimes of interest has elements of the form . They study the estimators IPWE and AIPWE for an optimal regime proposed in our 2012 paper (Zhang et al., 2012b), which are based on maximizing in inverse probability weighted estimators for the expected outcome, or value, under a regime in a specified class ; we have referred to estimators for an optimal regime found by maximizing an estimator for the value in as value search or policy search estimators. These are compared to two competing approaches. The first is the regression estimator RG, which is based on a posited parametric model for that induces the class of regimes when the model involves an interaction term of the form . The estimated optimal regime is found directly as . In the approach TCF call , a different estimator for the value from those in IPWE or AIPWE, given in their Equation (6), is maximized in . This method is proposed by us in Zhang et al. (2012a), in which we expressed (6) equivalently in terms an estimator for the contrast function . In particular, we suggested estimating an optimal regime of a specified form by maximizing in the estimator for the value given by , where is formed by representing in by a nonparametric estimator , such as support vector regression (Vapnik, Golowich, and Smola, 1997) or boosting (Freund and Schapire, 1997). TCF use random forests, noting that any flexible nonparametric estimator could be used. We thus disagree with TCF's characterization of this as a “regression” method and find reference to it as “RG with random forests” to be a bit misleading. This method, like IPWE and AIPWE, is a value search approach. These three methods are thus different in spirit and construction from RG, which bases the estimated optimal regime directly on a fitted regression model. We did not evaluate the performance of the contrast-based value search approach empirically in Zhang et al. (2012a), so the studies by TCF in which it is implemented using the particular choice of random forests, , fill an important gap and demonstrate its feasibility and robustness. For RG, TCF rightly consider misspecified parametric models that are closer to the true than the linear model we adopted to represent model misspecification in Zhang et al. (2012b), as would likely be formulated by a careful data analyst. We fully agree with their contention that RG can perform well under these conditions, as the simulations they present demonstrate. TCF also confirm our finding that IPWE is inferior to the other methods. The evidence from their studies along with that in our paper demonstrates that all of RG, AIPWE, and , and especially the latter two value search approaches, lead to high quality estimated regimes, providing the data analyst with a range of options. In fact, the analyst can employ competing approaches and compare the results to gain an understanding of sensitivity to modeling choices. A limitation of RG is that, as noted above, the class of regimes considered and the resulting estimated regimes are dictated by the form of the posited parametric regression model. On the other hand, if one were to use flexible nonparametric estimators like random forests to represent directly in the regression-based method, which seems to us an approach for which “” is a more appropriate acronym than its use by TCF, the result would be estimated regimes of a “black box” nature, which may elicit skepticism from clinicians. In contrast, the value search approaches, IPWE, AIPWE, and TCF's , search within a user-defined class of regimes whose specification need not be connected with the form of models for . This is advantageous if interest is in regimes having a specific form on the basis of interpretability, cost, or feasibility in practice that may not be induced straightforwardly from models for . For instance, as we demonstrated in Zhang et al. (2012b), the class of regimes can be restricted to have elements defined by rectangular regions; for example, , , which clinicians may find more interpretable than regimes involving linear combinations of covariates. TCF consider primarily the case of randomized studies, where the propensity scores are known and generally constant in . Here, IPWE and AIPWE are based on estimators for the value of a regime in that are guaranteed by construction to be consistent, which, intuitively, would be expected to lead to well-performing estimated optimal regimes. Moreover, these methods require no additional modeling, as the propensity score is estimated by the sample randomization proportion. The estimator for the value in (6) of TCF that forms the basis for is, in contrast, not consistent unless the model for is correctly specified, and the RG method depends critically on a correct model. As TCF demonstrate, this may be of little consequence with and a sufficiently flexible representation for or with RG and a “nearly correct” parametric model, although the evidence in TCF is less compelling for the latter estimator. Overall, we agree with TCF that the value search estimators AIPWE, incorporating a flexible model for in the “augmentation term,” and are the most promising in this setting. From a theoretical point of view, an advantage of AIPWE is that in this setting it yields the locally efficient estimator for the value; see Robins and Ritov (1997). In an observational study, AIPWE is based on a value estimator that is doubly robust; that is, guaranteed to be consistent as long as at least one of the propensity score model or model for is correctly specified, whereas, as TCF note, is not doubly robust. We agree with TCF that, if one has considerable confidence in the nonparametric random forest representation for the contrast function, including its incorporated adjustment for confounding, the additional protection afforded by the AIPWE may be unnecessary. However, AIPWE implemented with careful modeling of the propensity score in the same spirit as TCF propose in RG could provide the analyst with additional trust in the robustness of results. A challenge with all of the value search methods IPWE, AIPWE, and is that the maximization of the value estimator in is a nonsmooth optimization problem that cannot be addressed using standard optimization methods. In problems where the restricted class of regimes involves rich covariate information, so that is high-dimensional, implementation becomes computationally prohibitive and the quality of estimation will be degraded. One practical approach to circumventing this difficulty is described in Zhang et al. (2012a), where we demonstrated how the problem of maximizing value search estimators in can be recast as minimizing a weighted classification error; see also Zhao et al. (2012). Thus, estimation of an optimal treatment regime can be likened to a classification problem, viewing as a classifier, with the class of regimes determined by the choice of classifier; for example, classification and regression trees (Breiman et al., 1984) or support vector machines (Cortes and Vapnik, 1995). In this formulation, the “class label” and “weight” are functions of the estimated contrast function. Existing software for carrying out the minimization for a given choice of classifier can then be used to estimate an optimal regime in this class. Although this is also a nonstandard optimization problem, an advantage in practice is that computational techniques to approximate it efficiently and to carry out the variable selection involved are embedded in off-the-shelf software. A possible advantage of AIPWE over RG is the extension to more than one treatment decision point. The extension of RG, Q-learning, requires positing a sequence of regression models at each decision point that ideally must be compatible with one another. In practice, such a specification is almost impossible (but see Laber, Linn, and Stefanski, in press), so that the models at decision points other than the last one are almost certainly misspecified, even if flexible methods are used, which will compromise the quality of estimated regimes. The extension of AIPWE we present in Zhang et al. (2013) ideally requires specification of compatible such models, but only for the purpose of gaining efficiency and ensuring approximate double robustness. Extension of TCF's and related contrast-based value search estimators to this setting should be investigated. More generally, further research is needed to clarify the performance of approaches in the multiple decision setting. Given the well-performing options available for estimating optimal regimes, we believe that the most pressing challenge is that the methodological advances have far outpaced current practice. We must encourage our clinician collaborators and practicing biostatisticians to consider estimation of dynamic treatment regimes as a meaningful, primary data-analytic objective. Although this perspective has been embraced by some researchers in the behavioral sciences, it is not as prevalent in chronic disease research, where interest focuses primarily on identifying subgroups of patients to whom treatment may be targeted; that is, identifying the “right patient for the treatment.” Thinking in terms of optimal treatment regimes, so identifying “the right treatment for the patient,” offers a valuable complementary perspective. The critical next step for the treatment regime research community is a proactive effort to communicate the concepts and methods and their scientific relevance to health sciences researchers more broadly. That said, an outstanding methodological challenge is inference for the estimated regime. The value of an estimated regime is equivalent to the weighted test error of an estimated classifier and is thus a data-dependent, nonsmooth functional of the underlying generative distribution (Laber and Murphy, 2011; Chakraborty, Laber, and Zhao, 2014). Standard asymptotic methods for inference, including the bootstrap and series approximations, do not apply without modification, and the small sample performance of these methods can be quite poor under some generative models. Inference for the parameters indexing the optimal regime has been another focus for inference (Robins, 2004; Chakraborty, Murphy, and Strecher, 2010; Laber et al., 2014). However, it is not clear that this is an appropriate target for inference for value search estimators where the objective is to estimate a high-quality regime within a prespecified class, which need not be assumed to contain the true optimal regime. We thank TCF again for a thoughtful and important demonstration of the relative merits of estimators for optimal dynamic treatment regimes. Their findings, in conjunction with other work cited herein, make a strong case for the use of value search estimators in practice. Acknowledgements This work was supported by NIH grants P01 CA142538, R01 HL118336, and R01 CA085848. References Breiman, L, Freidman, J. L., Olshen, R. A., and Stone, C. J. (1984). Classification and Regression Trees. Belmont, California: Wadsworth. Chakraborty, B., Laber, E. B., and Zhao, Y. Q. (2014). Inference about the expected performance of a data-driven dynamic treatment regime. Clinical Trials 11, 408– 417. Chakraborty, B., Murphy, S., and Strecher, V. (2010). Inference for non-regular parameters in optimal dynamic treatment regimes. Statistical Methods in Medical Research 19, 317– 343. Cortes, C. and Vapnik, V. (1995). Support-vector networks. Machine Learning 20, 273– 297. Freund, B. and Schapire, R. E. (1997). A decision-theoretic generalization of on-line learning and an application to boosting. Journal of Computer and System Sciences 55, 119– 139. Laber, E. B., Linn, K. A., and Stefanski, L. A. (in press). Interactive model building for Q-learning. Biometrika. Laber, E. B., Lizotte, D. J., Qian, M., Pelham, W. E., and Murphy, S. A. (2014). Dynamic treatment regimes: Technical challenges and applications. Electronic Journal of Statistics 8, 1225– 1272. Laber, E. B. and Murphy, S. A. (2011). Adaptive confidence intervals for the test error in classification. Journal of the American Statistical Association 106, 904– 913. Robins, J. M. (2004). Optimal structural nested models for optimal sequential decisions. In Proceedings of the Second Seattle Symposium in Biostatistics, 189– 326. New York: Springer. Robins, J. M. and Ritov, Y. (1997). Toward a curse of dimensionality appropriate (CODA) asymptotic theory for semi-parametric models. Statistics in Medicine 16, 285– 319. Vapnik, V., Golowich, S., and Smola, A. (1997). Support vector regression for function approximation, regression estimation, and signal processing. Advances in Neural Information Processing Systems 9, 281– 287. Zhang, B., Tsiatis, A. A., Davidian, M., Zhang, M., and Laber, E. B. (2012a). Estimating optimal treatment regimes from a classification perspective. Stat 1, 103– 114. Zhang, B., Tsiatis, A. A., Laber, E. B., and Davidian, M. (2012b). A robust method for estimating optimal treatment regimes. Biometrics 68, 1010– 1018. Zhang, B., Tsiatis, A. A., Laber, E. B., and Davidian, M. (2013). Robust estimation of optimal dynamic treatment regimes for sequential treatment decisions. Biometrika 100, 681– 694. Zhao, Y., Zeng, D., Rush, A. J., and Kosorok, M. R. (2012). Estimating individualized treatment rules using outcome weighted learning. Journal of the American Statistical Association 107, 1106– 1118. Baqun Zhang School of Statistics Renmin University of China Beijing 100872, China email: zhangbaqun@ruc.edu.cn Anastasios A. Tsiatis Department of Statistics, Box 8203, North Carolina State University, Raleigh, North Carolina 27695, U.S.A. email: tsiatis@ncsu.edu Eric B. Laber Department of Statistics, Box 8203, North Carolina State University, Raleigh, North Carolina 27695, U.S.A. email: eblaber@ncsu.edu and Marie Davidian Department of Statistics, Box 8203, North Carolina State University, Raleigh, North Carolina 27695, U.S.A. email: davidian@ncsu.edu Volume71, Issue1March 2015Pages 267-273 ReferencesRelatedInformation
C2 - 4447210
DA - 2015///
PY - 2015///
DO - 10.1111/biom.12229
VL - 71
SP - 271–273
ER -
TY - CHAP
TI - Chapter 9: Value search estimators for optimal dynamic treatment regimes
AU - Davidian, Marie
AU - Tsiatis, Anastasios A.
AU - Laber, Eric B.
T2 - Adaptive Treatment Strategies in Practice
AB - 9.1 ▪ IntroductionThe area of personalized medicine is based on the premise that a patient's individual characteristics are implicated in which treatments are likely to benefit him/her. The most popular perspective on personalized medicine emphasizes identification of subgroups of patients who share certain characteristics, most often genetic/genomic features, and who are likely to benefit from a specific treatment. This goal understandably is of considerable interest in pharmaceutical research and in a regulatory context and has centered around development of biomarkers that can be used to identify such patients and targeting of new products to biomarker-defined subgroups. This point of view can be summarized as focusing on “the right patient for the treatment.”
PY - 2015/12/8/
DO - 10.1137/1.9781611974188.ch9
SP - 135-155
OP -
PB - Society for Industrial and Applied Mathematics
SN - 9781611974171 9781611974188
UR - http://dx.doi.org/10.1137/1.9781611974188.ch9
DB - Crossref
ER -
TY - JOUR
TI - Special issue on Bayesian nonparametrics
AU - Ghoshal, Subhashis
AU - Kleijn, Bas
AU - van der Vaart, Aad
AU - van Zanten, Harry
T2 - Journal of Statistical Planning and Inference
DA - 2015/11//
PY - 2015/11//
DO - 10.1016/J.JSPI.2015.04.008
VL - 166
SP - 1
J2 - Journal of Statistical Planning and Inference
LA - en
OP -
SN - 0378-3758
UR - http://dx.doi.org/10.1016/J.JSPI.2015.04.008
DB - Crossref
ER -
TY - JOUR
TI - Properties of Estimators in Exponential Family Settings with Observationbased Stopping Rules
AU - Milanzi, Elasma
AU - Molenberghs, Geert
T2 - Journal of Biometrics & Biostatistics
AB - Often, sample size is not fixed by design. A key example is a sequential trial with a stopping rule, where stopping is based on what has been observed at an interim look. While such designs are used for time and cost efficiency, and hypothesis testing theory has been well developed, estimation following a sequential trial is a challenging, still controversial problem. Progress has been made in the literature, predominantly for normal outcomes and/or for a deterministic stopping rule. Here, we place these settings in a broader context of outcomes following an exponential family distribution and, with a stochastic stopping rule that includes a deterministic rule and completely random sample size as special cases. It is shown that the estimation problem is usually simpler than often thought. In particular, it is established that the ordinary sample average is a very sensible choice, contrary to commonly encountered statements. We study (1) The so-called incompleteness property of the sufficient statistics, (2) A general class of linear estimators, and (3) Joint and conditional likelihood estimation. Apart from the general exponential family setting, normal and binary outcomes are considered as key examples. While our results hold for a general number of looks, for ease of exposition, we focus on the simple yet generic setting of two possible sample sizes, N=n or N=2n.
DA - 2015///
PY - 2015///
DO - 10.4172/2155-6180.1000272
VL - 07
IS - 01
J2 - J Biom Biostat
OP -
SN - 2155-6180
UR - http://dx.doi.org/10.4172/2155-6180.1000272
DB - Crossref
ER -
TY - JOUR
TI - On tests of activation map dimensionality for fMRI-based studies of learning
AU - Yang, Juemin
AU - Shmuelof, Lior
AU - Xiao, Luo
AU - Krakauer, John W.
AU - Caffo, Brian
T2 - Frontiers in Neuroscience
AB - A methodology for investigating learning is developed using activation distributions, as opposed to standard voxel-level interaction tests. The approach uses tests of dimensionality to consider the ensemble of paired changes in voxel activation. The developed method allows for the investigation of non-focal and non-localized changes due to learning. In exchange for increased power to detect learning-based changes, this procedure sacrifices the localization information gained via voxel-level interaction testing. The test is demonstrated on an arc-pointing motor task for the study of motor learning, which served as the motivation for this methodological development. The proposed framework considers activation distribution, while the specific proposed test investigates linear tests of dimensionality. This paper includes: the development of the framework, a large scale simulation study, and the subsequent application to a study of motor learning in healthy adults. While the performance of the method was excellent when model assumptions held, complications arose in instances of massive numbers of null voxels or varying angles of principal dimension across subjects. Further analysis found that careful masking addressed the former concern, while an angle correction successfully resolved the latter. The simulation results demonstrated that the study of linear dimensionality is able to capture learning effects. The motivating data set used to illustrate the method evaluates two similar arc-pointing tasks, each over two sessions, with training on only one of the tasks in between sessions. The results suggests different activation distribution dimensionality when considering the trained and untrained tasks separately. Specifically, the untrained task evidences greater activation distribution dimensionality than the trained task. However, the direct comparison between the two tasks did not yield a significant result. The nature of the indication for greater dimensionality in the untrained task is explored and found to be non-linear variation in the data.
DA - 2015/4//
PY - 2015/4//
DO - 10.3389/fnins.2015.00085
VL - 9
KW - canonical variates analysis
KW - cognitive learning
KW - BOLD fMRI
KW - statistical parametric mapping
KW - interaction test
ER -
TY - JOUR
TI - Movement prediction using accelerometers in a human population
AU - Xiao, Luo
AU - He, Bing
AU - Koster, Annemarie
AU - Caserotti, Paolo
AU - Lange-Maia, Brittney
AU - Glynn, Nancy W.
AU - Harris, Tamara B.
AU - Crainiceanu, Ciprian M.
T2 - Biometrics
AB - We introduce statistical methods for predicting the types of human activity at sub-second resolution using triaxial accelerometry data. The major innovation is that we use labeled activity data from some subjects to predict the activity labels of other subjects. To achieve this, we normalize the data across subjects by matching the standing up and lying down portions of triaxial accelerometry data. This is necessary to account for differences between the variability in the position of the device relative to gravity, which are induced by body shape and size as well as by the ambiguous definition of device placement. We also normalize the data at the device level to ensure that the magnitude of the signal at rest is similar across devices. After normalization we use overlapping movelets (segments of triaxial accelerometry time series) extracted from some of the subjects to predict the movement type of the other subjects. The problem was motivated by and is applied to a laboratory study of 20 older participants who performed different activities while wearing accelerometers at the hip. Prediction results based on other people's labeled dictionaries of activity performed almost as well as those obtained using their own labeled dictionaries. These findings indicate that prediction of activity types for data collected during natural activities of daily living may actually be possible.
DA - 2015/8//
PY - 2015/8//
DO - 10.1111/biom.12382
VL - 72
IS - 2
SP - 513-524
KW - Accelerometer
KW - Activity type
KW - Movelets
KW - Prediction
ER -
TY - JOUR
TI - On the sample covariance matrix estimator of reduced effective rank population matrices, with applications to fPCA
AU - Bunea, Florentina
AU - Xiao, Luo
T2 - Bernoulli
AB - This work provides a unified analysis of the properties of the sample covariance matrix $\Sigma_{n}$ over the class of $p\times p$ population covariance matrices $\Sigma$ of reduced effective rank $r_{e}(\Sigma)$. This class includes scaled factor models and covariance matrices with decaying spectrum. We consider $r_{e}(\Sigma)$ as a measure of matrix complexity, and obtain sharp minimax rates on the operator and Frobenius norm of $\Sigma_{n}-\Sigma$, as a function of $r_{e}(\Sigma)$ and $\|\Sigma\|_{2}$, the operator norm of $\Sigma$. With guidelines offered by the optimal rates, we define classes of matrices of reduced effective rank over which $\Sigma_{n}$ is an accurate estimator. Within the framework of these classes, we perform a detailed finite sample theoretical analysis of the merits and limitations of the empirical scree plot procedure routinely used in PCA. We show that identifying jumps in the empirical spectrum that consistently estimate jumps in the spectrum of $\Sigma$ is not necessarily informative for other goals, for instance for the selection of those sample eigenvalues and eigenvectors that are consistent estimates of their population counterparts. The scree plot method can still be used for selecting consistent eigenvalues, for appropriate threshold levels. We provide a threshold construction and also give a rule for checking the consistency of the corresponding sample eigenvectors. We specialize these results and analysis to population covariance matrices with polynomially decaying spectra, and extend it to covariance operators with polynomially decaying spectra. An application to fPCA illustrates how our results can be used in functional data analysis.
DA - 2015/5//
PY - 2015/5//
DO - 10.3150/14-bej602
VL - 21
IS - 2
SP - 1200-1230
KW - covariance matrix
KW - eigenvalue
KW - eigenvector
KW - fPCA
KW - high dimensions
KW - minimax rate
KW - optimal rate of convergence
KW - PCA
KW - scree plot
KW - sparsity
ER -
TY - JOUR
TI - Factors Associated with Parent Concern for Child Weight and Parenting Behaviors
AU - Peyer, Karissa L.
AU - Welk, Gregory
AU - Bailey-Davis, Lisa
AU - Yang, Shu
AU - Kim, Jae-Kwang
T2 - Childhood Obesity
AB - A parent's perception about their child's overweight status is an important precursor or determinant of preventative actions. Acknowledgment of, and concern for, overweight may be moderated by the parent's own weight status whereas engaging in healthy behaviors at home may promote healthy weight status. It is hypothesized that normal weight parents are more likely to engage in healthy behaviors and acknowledge overweight in their own children whereas heavier parents may report more concern about child weight.A total of 1745 parents of first- through fifth-grade students completed a questionnaire assessing reactions to a school BMI report and perceptions about BMI issues. Specific items included perceptions of child's weight status, concern for child weight status, and preventive practices. Parents also provided information about their own weight status. Relationships between measured child weight, perceived child weight, parent weight, parent concern, and healthy behaviors were examined.Overweight parents were more likely to identify overweight in their child and report concern about their child's weight. Concern was higher for parents of overweight children than of normal weight children. Normal weight parents and parents of normal weight children reported more healthy behaviors.Results support the hypothesis that normal weight parents are more likely to engage in healthy behaviors and that overweight parents are more likely to report concern about child weight. However, overweight parents are also more likely to acknowledge overweight status in their own child. Future research should examine links between parent concern and actual pursuit of weight management assistance.
DA - 2015/6//
PY - 2015/6//
DO - 10.1089/chi.2014.0111
VL - 11
IS - 3
SP - 269-274
J2 - Childhood Obesity
LA - en
OP -
SN - 2153-2168 2153-2176
UR - http://dx.doi.org/10.1089/chi.2014.0111
DB - Crossref
ER -
TY - JOUR
TI - Likelihood-based Inference with Missing Data Under Missing-at-Random
AU - Yang, Shu
AU - Kim, Jae Kwang
T2 - Scandinavian Journal of Statistics
AB - Abstract Likelihood‐based inference with missing data is challenging because the observed log likelihood is often an (intractable) integration over the missing data distribution, which also depends on the unknown parameter. Approximating the integral by Monte Carlo sampling does not necessarily lead to a valid likelihood over the entire parameter space because the Monte Carlo samples are generated from a distribution with a fixed parameter value. We consider approximating the observed log likelihood based on importance sampling. In the proposed method, the dependency of the integral on the parameter is properly reflected through fractional weights. We discuss constructing a confidence interval using the profile likelihood ratio test. A Newton–Raphson algorithm is employed to find the interval end points. Two limited simulation studies show the advantage of the Wilks inference over the Wald inference in terms of power, parameter space conformity and computational efficiency. A real data example on salamander mating shows that our method also works well with high‐dimensional missing data.
DA - 2015/10/19/
PY - 2015/10/19/
DO - 10.1111/sjos.12184
VL - 43
IS - 2
SP - 436-454
J2 - Scand J Statist
LA - en
OP -
SN - 0303-6898
UR - http://dx.doi.org/10.1111/sjos.12184
DB - Crossref
KW - confidence interval
KW - fractional imputation
KW - likelihood ratio
KW - nonresponse
KW - profile likelihood ratio
ER -
TY - JOUR
TI - Longitudinal functional data analysis
AU - Park, So Young
AU - Staicu, Ana-Maria
T2 - Stat
AB - We consider dependent functional data that are correlated because of a longitudinal‐based design: each subject is observed at repeated times and at each time, a functional observation (curve) is recorded. We propose a novel parsimonious modelling framework for repeatedly observed functional observations that allows to extract low‐dimensional features. The proposed methodology accounts for the longitudinal design, is designed to study the dynamic behaviour of the underlying process, allows prediction of full future trajectory and is computationally fast. Theoretical properties of this framework are studied, and numerical investigations confirm excellent behaviour in finite samples. The proposed method is motivated by and applied to a diffusion tensor imaging study of multiple sclerosis. Copyright © 2015 John Wiley & Sons, Ltd.
DA - 2015/2//
PY - 2015/2//
DO - 10.1002/STA4.89
VL - 4
IS - 1
SP - 212-226
J2 - STAT
LA - en
OP -
SN - 2049-1573
UR - http://dx.doi.org/10.1002/STA4.89
DB - Crossref
KW - dependent functional data
KW - diffusion tensor imaging
KW - functional principal component analysis
KW - longitudinal design
KW - multiple sclerosis
ER -
TY - JOUR
TI - Comment
AU - Zhang, Yichi
AU - Laber, Eric B.
T2 - Journal of the American Statistical Association
AB - Click to increase image sizeClick to decrease image size Additional informationNotes on contributorsYichi ZhangYichi Zhang (E-mail: yzhang52@ncsu.edu), and Eric Laber (E-mail: laber@stat.ncsu.edu), Department of Statistics, North Carolina State University, 2311 Stinson Drive, SAS Hall, Raleigh, NC 27695.Eric B. LaberYichi Zhang (E-mail: yzhang52@ncsu.edu), and Eric Laber (E-mail: laber@stat.ncsu.edu), Department of Statistics, North Carolina State University, 2311 Stinson Drive, SAS Hall, Raleigh, NC 27695.
DA - 2015/10/2/
PY - 2015/10/2/
DO - 10.1080/01621459.2015.1106403
VL - 110
IS - 512
SP - 1451-1454
J2 - Journal of the American Statistical Association
LA - en
OP -
SN - 0162-1459 1537-274X
UR - http://dx.doi.org/10.1080/01621459.2015.1106403
DB - Crossref
ER -
TY - JOUR
TI - On sparse representation for optimal individualized treatment selection with penalized outcome weighted learning
AU - Song, Rui
AU - Kosorok, Michael
AU - Zeng, Donglin
AU - Zhao, Yingqi
AU - Laber, Eric
AU - Yuan, Ming
T2 - Stat
AB - As a new strategy for treatment, which takes individual heterogeneity into consideration, personalized medicine is of growing interest. Discovering individualized treatment rules for patients who have heterogeneous responses to treatment is one of the important areas in developing personalized medicine. As more and more information per individual is being collected in clinical studies and not all of the information is relevant for treatment discovery, variable selection becomes increasingly important in discovering individualized treatment rules. In this article, we develop a variable selection method based on penalized outcome weighted learning through which an optimal treatment rule is considered as a classification problem where each subject is weighted proportional to his or her clinical outcome. We show that the resulting estimator of the treatment rule is consistent and establish variable selection consistency and the asymptotic distribution of the estimators. The performance of the proposed approach is demonstrated via simulation studies and an analysis of chronic depression data. Copyright © 2015 John Wiley & Sons, Ltd.
DA - 2015/2//
PY - 2015/2//
DO - 10.1002/STA4.78
VL - 4
IS - 1
SP - 59-68
J2 - STAT
LA - en
OP -
SN - 2049-1573
UR - http://dx.doi.org/10.1002/STA4.78
DB - Crossref
KW - penalization
KW - personalized medicine
KW - support vector machine
ER -
TY - JOUR
TI - Using pilot data to size a two-arm randomized trial to find a nearly optimal personalized treatment strategy
AU - Laber, Eric B.
AU - Zhao, Ying-Qi
AU - Regh, Todd
AU - Davidian, Marie
AU - Tsiatis, Anastasios
AU - Stanford, Joseph B.
AU - Zeng, Donglin
AU - Song, Rui
AU - Kosorok, Michael R.
T2 - Statistics in Medicine
AB - A personalized treatment strategy formalizes evidence-based treatment selection by mapping patient information to a recommended treatment. Personalized treatment strategies can produce better patient outcomes while reducing cost and treatment burden. Thus, among clinical and intervention scientists, there is a growing interest in conducting randomized clinical trials when one of the primary aims is estimation of a personalized treatment strategy. However, at present, there are no appropriate sample size formulae to assist in the design of such a trial. Furthermore, because the sampling distribution of the estimated outcome under an estimated optimal treatment strategy can be highly sensitive to small perturbations in the underlying generative model, sample size calculations based on standard (uncorrected) asymptotic approximations or computer simulations may not be reliable. We offer a simple and robust method for powering a single stage, two-armed randomized clinical trial when the primary aim is estimating the optimal single stage personalized treatment strategy. The proposed method is based on inverting a plugin projection confidence interval and is thereby regular and robust to small perturbations of the underlying generative model. The proposed method requires elicitation of two clinically meaningful parameters from clinical scientists and uses data from a small pilot study to estimate nuisance parameters, which are not easily elicited. The method performs well in simulated experiments and is illustrated using data from a pilot study of time to conception and fertility awareness.
DA - 2015/10/28/
PY - 2015/10/28/
DO - 10.1002/SIM.6783
VL - 35
IS - 8
SP - 1245-1256
J2 - Statist. Med.
LA - en
OP -
SN - 0277-6715
UR - http://dx.doi.org/10.1002/SIM.6783
DB - Crossref
KW - personalized medicine
KW - sample size calculation
KW - treatment regimes
KW - nonregular asymptotics
KW - projection confidence region
ER -
TY - JOUR
TI - Convex Clustering: An Attractive Alternative to Hierarchical Clustering
AU - Chen, Gary K.
AU - Chi, Eric C.
AU - Ranola, John M.O.
AU - Lange, Kenneth
T2 - PLoS Computational Biology
AB - The primary goal in cluster analysis is to discover natural groupings of objects. The field of cluster analysis is crowded with diverse methods that make special assumptions about data and address different scientific aims. Despite its shortcomings in accuracy, hierarchical clustering is the dominant clustering method in bioinformatics. Biologists find the trees constructed by hierarchical clustering visually appealing and in tune with their evolutionary perspective. Hierarchical clustering operates on multiple scales simultaneously. This is essential, for instance, in transcriptome data where one may be interested in making qualitative inferences about how lower-order relationships like gene modules lead to higher-order relationships like pathways or biological processes. The recently developed method of convex clustering preserves the visual appeal of hierarchical clustering while ameliorating its propensity to make false inferences in the presence of outliers and noise. The current paper exploits the proximal distance principle to construct a novel algorithm for solving the convex clustering problem. The solution paths generated by convex clustering reveal relationships between clusters that are hidden by static methods such as k-means clustering. Our convex clustering software separates parameters, accommodates missing data, and supports prior information on relationships. The software is implemented on ATI and nVidia graphics processing units (GPUs) for maximal speed. Several biological examples illustrate the strengths of convex clustering and the ability of the proximal distance algorithm to handle high-dimensional problems.
DA - 2015/5/12/
PY - 2015/5/12/
DO - 10.1371/journal.pcbi.1004228
VL - 11
IS - 5
SP - e1004228
UR - http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1004228
ER -
TY - JOUR
TI - Splitting Methods for Convex Clustering
AU - Chi, Eric C.
AU - Lange, Kenneth
T2 - Journal of Computational and Graphical Statistics
AB - Clustering is a fundamental problem in many scientific applications. Standard methods such as $k$-means, Gaussian mixture models, and hierarchical clustering, however, are beset by local minima, which are sometimes drastically suboptimal. Recently introduced convex relaxations of $k$-means and hierarchical clustering shrink cluster centroids toward one another and ensure a unique global minimizer. In this work we present two splitting methods for solving the convex clustering problem. The first is an instance of the alternating direction method of multipliers (ADMM); the second is an instance of the alternating minimization algorithm (AMA). In contrast to previously considered algorithms, our ADMM and AMA formulations provide simple and unified frameworks for solving the convex clustering problem under the previously studied norms and open the door to potentially novel norms. We demonstrate the performance of our algorithm on both simulated and real data examples. While the differences between the two algorithms appear to be minor on the surface, complexity analysis and numerical experiments show AMA to be significantly more efficient.
DA - 2015/12/10/
PY - 2015/12/10/
DO - 10.1080/10618600.2014.948181
VL - 24
IS - 4
SP - 994-1013
UR - http://www.tandfonline.com/doi/abs/10.1080/10618600.2014.948181
KW - Alternating direction method of multipliers
KW - Alternating minimization algorithm
KW - Convex optimization
KW - Hierarchical clustering
KW - k-means
KW - Regularization paths
ER -
TY - JOUR
TI - High dimension low sample size asymptotics of robust PCA
AU - Zhou, Yi-Hui
AU - Marron, JS
AU - others
T2 - Electronic Journal of Statistics
DA - 2015///
PY - 2015///
VL - 9
IS - 1
SP - 204-218
ER -
TY - JOUR
TI - Metabolomic evaluation of neutrophilic airway inflammation in cystic fibrosis
T2 - Chest
DA - 2015///
PY - 2015///
VL - 148
IS - 2
SP - 507-515
ER -
TY - JOUR
TI - The projack: a resampling approach to correct for ranking bias in high-throughput studies
AU - Zhou, Yi-Hui
AU - Wright, Fred A
T2 - Biostatistics
DA - 2015///
PY - 2015///
VL - 17
IS - 1
SP - 54-64
ER -
TY - JOUR
TI - Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis
AU - Corvol, Harriet
AU - Blackman, Scott M
AU - Boëlle, Pierre-Yves
AU - Gallins, Paul J
AU - Pace, Rhonda G
AU - Stonebraker, Jaclyn R
AU - Accurso, Frank J
AU - Clement, Annick
AU - Collaco, Joseph M
AU - Dang, Hong
AU - others
T2 - Nature communications
DA - 2015///
PY - 2015///
VL - 6
SP - 8382
ER -
TY - JOUR
TI - Population-based in vitro hazard and concentration--response assessment of chemicals: the 1000 genomes high-throughput screening study
AU - Abdo, Nour
AU - Xia, Menghang
AU - Brown, Chad C
AU - Kosyk, Oksana
AU - Huang, Ruili
AU - Sakamuru, Srilatha
AU - Zhou, Yi-Hui
AU - Jack, John R
AU - Gallins, Paul
AU - Xia, Kai
AU - others
T2 - Environmental health perspectives
DA - 2015///
PY - 2015///
VL - 123
IS - 5
SP - 458
ER -
TY - JOUR
TI - PathwaySeq: Pathway analysis for RNA-Seq data using a score-based approach
AU - Zhou, Yihui
T2 - dim (data. test)
DA - 2015///
PY - 2015///
VL - 1
IS - 1000
SP - 448
ER -
TY - JOUR
TI - Identification of novel gene targets and putative regulators of arsenic-associated DNA methylation in human urothelial cells and bladder cancer
T2 - Chemical research in toxicology
DA - 2015///
PY - 2015///
VL - 28
IS - 6
SP - 1144-1155
ER -
TY - JOUR
TI - Epigenome-wide association study (EWAS) of BMI, BMI change and waist circumference in African American adults identifies multiple replicated loci
AU - Demerath, Ellen W
AU - Guan, Weihua
AU - Grove, Megan L
AU - Aslibekyan, Stella
AU - Mendelson, Michael
AU - Zhou, Yi-Hui
AU - Hedman, Åsa K
AU - Sandling, Johanna K
AU - Li, Li-An
AU - Irvin, Marguerite R
AU - others
T2 - Human molecular genetics
DA - 2015///
PY - 2015///
VL - 24
IS - 15
SP - 4464-4479
ER -
TY - JOUR
TI - Effect of predicted protein-truncating genetic variants on the human transcriptome
AU - Rivas, Manuel A
AU - Pirinen, Matti
AU - Conrad, Donald F
AU - Lek, Monkol
AU - Tsang, Emily K
AU - Karczewski, Konrad J
AU - Maller, Julian B
AU - Kukurba, Kimberly R
AU - DeLuca, David S
AU - Fromer, Menachem
AU - others
T2 - Science
DA - 2015///
PY - 2015///
VL - 348
IS - 6235
SP - 666-669
ER -
TY - JOUR
TI - Gene expression in transformed lymphocytes reveals variation in endomembrane and HLA pathways modifying cystic fibrosis pulmonary phenotypes
AU - O’Neal, Wanda K
AU - Gallins, Paul
AU - Pace, Rhonda G
AU - Dang, Hong
AU - Wolf, Whitney E
AU - Jones, Lisa C
AU - Guo, XueLiang
AU - Zhou, Yi-Hui
AU - Madar, Vered
AU - Huang, Jinyan
AU - others
T2 - The American Journal of Human Genetics
DA - 2015///
PY - 2015///
VL - 96
IS - 2
SP - 318-328
ER -
TY - JOUR
TI - Glacier Terminus Estimation from Landsat Image Intensity Profiles
AU - Usset, Joseph
AU - Maity, Arnab
AU - Staicu, Ana-Maria
AU - Schwartzman, Armin
T2 - Journal of Agricultural, Biological, and Environmental Statistics
DA - 2015/5/6/
PY - 2015/5/6/
DO - 10.1007/S13253-015-0207-4
VL - 20
IS - 2
SP - 279-298
J2 - JABES
LA - en
OP -
SN - 1085-7117 1537-2693
UR - http://dx.doi.org/10.1007/S13253-015-0207-4
DB - Crossref
KW - Change-point estimation
KW - Cross-validation
KW - Nonparametric regression
KW - Satellite imagery
KW - Spline smoothing
ER -
TY - JOUR
TI - Unified variable selection in semi-parametric models
AU - Terry, W.
AU - Zhang, H.
AU - Maity, A.
AU - Arshad, H.
AU - Karmaus, W.
T2 - Statistical Methods in Medical Research
AB - We propose a Bayesian variable selection method in semi-parametric models with applications to genetic and epigenetic data (e.g., single nucleotide polymorphisms and DNA methylation, respectively). The data are individually standardized to reduce heterogeneity and facilitate simultaneous selection of categorical (single nucleotide polymorphisms) and continuous (DNA methylation) variables. The Gaussian reproducing kernel is applied to the transformed data to evaluate joint effect of the variables, which may include complex interactions between, e.g., single nucleotide polymorphisms and DNA methylation. Indicator variables are introduced to the model for the purpose of variable selection. The method is demonstrated and evaluated using simulations under different scenarios. We apply the method to identify informative DNA methylation sites and single nucleotide polymorphisms in a set of genes based on their joint effect on allergic sensitization. The selected single nucleotide polymorphisms and methylation sites have the potential to serve as early markers for allergy prediction, and consequently benefit medical and clinical research to prevent allergy before its manifestation.
DA - 2015/10//
PY - 2015/10//
DO - 10.1177/0962280215610928
VL - 10
IS - 6
SP - 2821–2831
KW - Bayesian methods
KW - Gaussian kernel
KW - non-linear effects
KW - transformation
KW - reproducing kernel
KW - variable selection
KW - single nucleotide polymorphisms
KW - DNA methylation
ER -
TY - CONF
TI - Data-driven personas: Constructing archetypal users with clickstreams and user telemetry
AU - Zhang, X.
AU - Brown, H. F.
AU - Shankar, A.
C2 - 2015///
C3 - 34th Annual CHI Conference on Human Factors in Computing Systems, CHI 2016
DA - 2015///
SP - 5350-5359
ER -
TY - CONF
TI - Stormwater Treatment Performance of a Permeable Pavement-Biofiltration System and a Stand-Alone Biofiltration Unit in North Carolina
AU - Anderson, A. R.
AU - Smolek, A. P.
AU - Hunt, W. F.
T2 - International Low Impact Development 2015
AB - A BioPave treatment train was retrofitted in an existing parking lot in Fayetteville, North Carolina, USA. The BioPave treatment train comprises a permeable pavement and Filterra devices in series. Additionally, a stand-alone Filterra biofiltration device was installed at the same site to evaluate its performance in treating pollutants of concern in North Carolina and elsewhere. The purpose of this study is to gain insight into the water quality treatment capabilities of a PICP—flow-through filter treatment train and to evaluate the stand-alone device's hydrologic and water quality performance. Automated, flow-proportional water quality samplers were installed to collect samples at multiple locations at each SCM. It was seen that the Filterra stand-alone device had sediment concentration reductions above 95% for both TSS and SSC. For nutrients, the Filterra reduced the percent total phosphorus and total nitrogen concentrations by a median of 62 and 33%, respectively. Overall the system treated the 1-in. design storm before significant overflow occurred and showed a similar watershed characteristics to predeveloped conditions. The BioPave system removed sediment, nitrogen, and phosphorus well despite having some moderate to severe clogging issues throughout the study, resulting in load reductions of 69, 84, and 72% by mass for nitrogen, phosphorus, and sediment, primarily through the mechanism of infiltration into the sandy loam underlying soils beneath the pavers.
C2 - 2015/1/12/
C3 - International Low Impact Development Conference 2015
DA - 2015/1/12/
DO - 10.1061/9780784479025.022
SP - 216-226
PB - American Society of Civil Engineers
SN - 9780784479025
UR - http://dx.doi.org/10.1061/9780784479025.022
DB - Crossref
ER -
TY - CONF
TI - A collaborative approach to voluntary watershed restoration in coastal North Carolina
AU - Carey, E. S.
AU - Page, J. L.
AU - Shew, R. D.
AU - Hunt, W. F.
C2 - 2015///
C3 - LID: It Works In All Climates and Soils
DA - 2015///
SP - 404-410
ER -
TY - JOUR
TI - Spatial Bayesian Nonparametric Methods
AU - Reich, Brian James
AU - Fuentes, Montserrat
T2 - NONPARAMETRIC BAYESIAN INFERENCE IN BIOSTATISTICS
DA - 2015///
PY - 2015///
DO - 10.1007/978-3-319-19518-6_17
SP - 347-357
ER -
TY - JOUR
TI - Identification of resistance to the Ga1-m gametophyte factor in maize
AU - Jones, Zachary G.
AU - Goodman, Major M.
AU - Krakowsky, Matthew D.
T2 - EUPHYTICA
DA - 2015/12//
PY - 2015/12//
DO - 10.1007/s10681-015-1518-9
VL - 206
IS - 3
SP - 785-791
SN - 1573-5060
KW - Gametophyte Factors
KW - Ga1
KW - Maize
KW - Popcorn
ER -
TY - JOUR
TI - Using Decision Lists to Construct Interpretable and Parsimonious Treatment Regimes
AU - Zhang, Yichi
AU - Laber, Eric B.
AU - Tsiatis, Anastasios
AU - Davidian, Marie
T2 - BIOMETRICS
AB - Summary A treatment regime formalizes personalized medicine as a function from individual patient characteristics to a recommended treatment. A high-quality treatment regime can improve patient outcomes while reducing cost, resource consumption, and treatment burden. Thus, there is tremendous interest in estimating treatment regimes from observational and randomized studies. However, the development of treatment regimes for application in clinical practice requires the long-term, joint effort of statisticians and clinical scientists. In this collaborative process, the statistician must integrate clinical science into the statistical models underlying a treatment regime and the clinician must scrutinize the estimated treatment regime for scientific validity. To facilitate meaningful information exchange, it is important that estimated treatment regimes be interpretable in a subject-matter context. We propose a simple, yet flexible class of treatment regimes whose members are representable as a short list of if–then statements. Regimes in this class are immediately interpretable and are therefore an appealing choice for broad application in practice. We derive a robust estimator of the optimal regime within this class and demonstrate its finite sample performance using simulation experiments. The proposed method is illustrated with data from two clinical trials.
DA - 2015/12//
PY - 2015/12//
DO - 10.1111/biom.12354
VL - 71
IS - 4
SP - 895-904
SN - 1541-0420
KW - Decision lists
KW - Exploratory analyses
KW - Interpretability
KW - Personalized medicine
KW - Treatment regimes
ER -
TY - JOUR
TI - Observations of Cerceris fumipennis (Hymenoptera: Crabronidae) phenology and variation in its buprestid prey in Louisiana
AU - Johnson, C. W.
AU - MacRae, T. C.
AU - Brownie, C.
AU - Virgets, W.
AU - Allison, J. D.
T2 - Florida Entomologist
AB - The non-native emerald ash borer, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), threatens extirpation of susceptible ash (Fraxinus species; Lamiales: Oleaceae) in North America. Cerceris fumipennis Say (Hymenoptera: Crabronidae), a ground-nesting wasp that preys on Buprestidae in eastern North America, is used as a survey tool for the emerald ash borer in the northeastern U.S. and Canada. The recent detection of the emerald ash borer in Louisiana provides an opportunity to complement trapping surveys with the use of C. fumipennis, but knowledge of C. fumipennis in the region is lacking. From 2011 to 2014, we conducted searches at 155 sites and located C. fumipennis aggregations at 25% (n = 39) of these sites; 36% (n = 14) of these were located at forest harvests, an aggregation habitat not previously reported in the literature. We collected 1,559 buprestids representing 35 species from 2 aggregations in Louisiana between May and Aug 2012. Buprestid collections at these aggregations and observations of C. fumipennis activity at a 3rd aggregation indicated the number of buprestid species and individuals collected declined significantly from May to Jul. We collected significantly more Agrilus difficilis Gory (Coleoptera: Buprestidae) in the afternoon than morning hours and observed similar diurnal patterns among other buprestid species during the early weeks following aggregation activation. We also discuss evidence suggesting a portion of the regional C. fumipennis population is bivoltine. Although A. planipennis was not collected during this study, our results suggest that C. fumipennis is a feasible sampling tool and a useful addition to ongoing emerald ash borer surveys in the region.
DA - 2015///
PY - 2015///
DO - 10.1653/024.098.0415
VL - 98
IS - 4
SP - 1106-1113
ER -
TY - JOUR
TI - Impacts of switchgrass-loblolly pine intercropping on soil physical properties of a drained forest
AU - Cacho, J. F.
AU - Youssef, M. A.
AU - Chescheir, G. M.
AU - Skaggs, R. W.
AU - Leggett, Z. H.
AU - Sucre, E. B.
AU - Nettles, J. E.
AU - Arellano, C.
T2 - Transactions of the ASABE
AB - Intercropping switchgrass ( L.) with managed loblolly pine ( L.) has been proposed as an alternative source of bioenergy feedstock that does not require conversion of agricultural cropland. Different management practices may alter soil physical properties (SPP), which could influence productivity, hydrologic and biogeochemical processes. Therefore, we investigated the effect of switchgrass-loblolly pine intercropping on the SPP of a poorly drained forest soil in eastern North Carolina using three management regimes: young loblolly pine stand (PINE), switchgrass-pine intercropping (PSWITCH), and a 38-year-old loblolly pine stand (REF). Measurements of SPP were conducted before and after the third annual harvesting operation using intact soil cores taken from three points within each of three replicated plots and at three depths: 0-15 cm, 15-30 cm, and 30-45 cm. Pre- and post-harvest values of SPP in PSWITCH were not significantly different. Compared to PINE, changes in bulk density and in both total porosity and saturated hydraulic conductivity in PSWITCH were significant only in the top 30 and 15 cm of soil, respectively. Volume drained and drainable porosity in PSWITCH decreased significantly at water table depths â¤45 cm. Cumulative effects of V-shearing for switchgrass seedbed preparation and the first and second harvest operations may have caused structural changes to the surface soil layer in PSWITCH that subsequently resulted in the measured differences in SPP between PSWITCH and PINE. We suggest that soil disturbance should be minimized during field operations to lessen the adverse effects on SPP, and models used to quantify impacts of management practices and land use change on the hydrology and biogeochemistry of managed forests should consider SPP changes caused by management regimes.
DA - 2015///
PY - 2015///
DO - 10.13031/trans.58.11238
VL - 58
IS - 6
SP - 1573-1583
ER -
TY - JOUR
TI - General weighted optimality of designed experiments
AU - Stallings, J. W.
AU - Morgan, J. P.
T2 - BIOMETRIKA
AB - Journal Article General weighted optimality of designed experiments Get access J. W. Stallings, J. W. Stallings Department of Statistics, North Carolina State University, Raleigh, North Carolina 27695, U.S.A. jwstalli@ncsu.edu Search for other works by this author on: Oxford Academic Google Scholar J. P. Morgan J. P. Morgan Department of Statistics, Virginia Tech, Blacksburg, Virginia 24061, U.S.A., jpmorgan@vt.edu Search for other works by this author on: Oxford Academic Google Scholar Biometrika, Volume 102, Issue 4, December 2015, Pages 925–935, https://doi.org/10.1093/biomet/asv037 Published: 28 September 2015 Article history Received: 01 September 2014 Revision received: 01 May 2015 Published: 28 September 2015
DA - 2015/12//
PY - 2015/12//
DO - 10.1093/biomet/asv037
VL - 102
IS - 4
SP - 925-935
SN - 1464-3510
KW - A-optimality
KW - Baseline parameterization
KW - Optimal design
KW - Weighted information matrix
KW - Weighted optimality
KW - Weighted variance
ER -
TY - JOUR
TI - Forward Stagewise Shrinkage and Addition for High Dimensional Censored Regression
AU - Guo, Zifang
AU - Lu, Wenbin
AU - Li, Lexin
T2 - STATISTICS IN BIOSCIENCES
AB - Despite enormous development on variable selection approaches in recent years, modeling and selection of high dimensional censored regression remains a challenging question. When the number of predictors p far exceeds the number of observational units n and the outcome is censored, computations of existing solutions often become difficult, or even infeasible in some situations, while performances frequently deteriorate. In this article, we aim at simultaneous model estimation and variable selection for Cox proportional hazards models with high dimensional covariates. We propose a forward stage-wise shrinkage and addition approach for that purpose. Our proposal extends a popular statistical learning technique, the boosting method. It inherits the flexible nature of boosting and is straightforward to extend to nonlinear Cox models. Meanwhile it advances the classical boosting method by adding explicit variable selection and substantially reducing the number of iterations to the algorithm convergence. Our intensive simulations have showed that the new method enjoys a competitive performance in Cox models with both p < n and p ≥ n scenarios. The new method was also illustrated with analysis of two real microarray survival datasets.
DA - 2015/10//
PY - 2015/10//
DO - 10.1007/s12561-014-9114-4
VL - 7
IS - 2
SP - 225-244
SN - 1867-1772
KW - Adaptive LASSO
KW - Boosting
KW - Forward stagewise regression
KW - Proportional hazards model
KW - Variable selection
ER -
TY - JOUR
TI - Estimation After a Group Sequential Trial
AU - Milanzi, Elasma
AU - Molenberghs, Geert
AU - Alonso, Ariel
AU - Kenward, Michael G.
AU - Tsiatis, Anastasios A.
AU - Davidian, Marie
AU - Verbeke, Geert
T2 - STATISTICS IN BIOSCIENCES
AB - Group sequential trials are one important instance of studies for which the sample size is not fixed a priori but rather takes one of a finite set of pre-specified values, dependent on the observed data. Much work has been devoted to the inferential consequences of this design feature. Molenberghs et al. (Statistical Methods in Medical Research, 2012) and Milanzi et al. (Properties of estimators in exponential family settings with observation-based stopping rules, 2012) reviewed and extended the existing literature, focusing on a collection of seemingly disparate, but related, settings, namely completely random sample sizes, group sequential studies with deterministic and random stopping rules, incomplete data, and random cluster sizes. They showed that the ordinary sample average is a viable option for estimation following a group sequential trial, for a wide class of stopping rules and for random outcomes with a distribution in the exponential family. Their results are somewhat surprising in the sense that the sample average is not optimal, and further, there does not exist an optimal, or even, unbiased linear estimator. However, the sample average is asymptotically unbiased, both conditionally upon the observed sample size as well as marginalized over it. By exploiting ignorability they showed that the sample average is the conventional maximum likelihood estimator. They also showed that a conditional maximum likelihood estimator is finite sample unbiased, but is less efficient than the sample average and has the larger mean squared error. Asymptotically, the sample average and the conditional maximum likelihood estimator are equivalent. This previous work is restricted, however, to the situation in which the the random sample size can take only two values, $$N=n$$ or $$N=2n$$ . In this paper, we consider the more practically useful setting of sample sizes in a the finite set $$\{n_1,n_2,\dots ,n_L\}$$ . It is shown that the sample average is then a justifiable estimator , in the sense that it follows from joint likelihood estimation, and it is consistent and asymptotically unbiased. We also show why simulations can give the false impression of bias in the sample average when considered conditional upon the sample size. The consequence is that no corrections need to be made to estimators following sequential trials. When small-sample bias is of concern, the conditional likelihood estimator (CLE) provides a relatively straightforward modification to the sample average. Finally, it is shown that classical likelihood-based standard errors and confidence intervals can be applied, obviating the need for technical corrections.
DA - 2015/10//
PY - 2015/10//
DO - 10.1007/s12561-014-9112-6
VL - 7
IS - 2
SP - 187-205
SN - 1867-1772
KW - Exponential family
KW - Frequentist inference
KW - Generalized sample average
KW - Joint modeling
KW - Likelihood inference
KW - Missing at random
KW - Sample average
ER -
TY - JOUR
TI - Consistent testing for recurrent genomic aberrations
AU - Walter, V.
AU - Wright, F. A.
AU - Nobel, A. B.
T2 - BIOMETRIKA
AB - We consider the detection and identification of recurrent departures from stationary behaviour in genomic or similarly arranged data containing measurements at an ordered set of variables. Our primary focus is on departures that occur only at a single variable, or within a small window of contiguous variables, but involve more than one sample. This encompasses the identification of aberrant markers in genome-wide measurements of DNA copy number and DNA methylation, as well as meta-analyses of genome-wide association studies. We propose and analyse a cyclic shift-based procedure for testing recurrent departures from stationarity. Our analysis establishes the consistency of cyclic shift [Formula: see text]-values for datasets with a fixed set of samples as the number of observed variables tends to infinity, under the assumption that each sample is an independent realization of a stationary Markov chain. Our results apply to any test statistic satisfying a simple invariance condition.
DA - 2015/12//
PY - 2015/12//
DO - 10.1093/biomet/asv046
VL - 102
IS - 4
SP - 783-796
SN - 1464-3510
KW - Consistency
KW - DNA copy number
KW - DNA methylation
KW - Genome-wide association study
KW - Hypothesis testing
ER -
TY - JOUR
TI - Adaptive Bayesian procedures using random series priors
AU - Shen, W. N.
AU - Ghosal, S.
T2 - Scandinavian Journal of Statistics: Theory and Applications
DA - 2015///
PY - 2015///
VL - 42
IS - 4
SP - 1194-1213
ER -
TY - JOUR
TI - Further re-analyses looking for effects of phylogenetic diversity on community biomass and stability
AU - Cardinale, Bradley J.
AU - Venail, Patrick
AU - Gross, Kevin
AU - Oakley, Todd H.
AU - Narwani, Anita
AU - Allan, Eric
AU - Flombaum, Pedro
AU - Joshi, Jasmin
AU - Reich, Peter B.
AU - Tilman, David
AU - Ruijven, Jasper
T2 - FUNCTIONAL ECOLOGY
AB - Species richness (SR) and phylogenetic diversity (PD) are highly correlated measures of plant diversity. Each, by itself, is significantly associated with plant community biomass in biodiversity experiments. As presented by Cadotte (2015) and as we present below, reasonable but alternative analyses that attempt to control for this correlation in different ways provide contradictory or inconclusive support for the hypothesis that PD is superior to SR as a predictor of community biomass. In Venail et al. (2015), we re-analysed data from 16 experimental manipulations of grassland SR to look at how SR and PD influence variation in plant community biomass through time. Using four types of analyses, we showed that, after statistically controlling for variation in SR, PD was not related to community biomass or to the temporal stability of biomass. We did, however, find that SR tends to increase the biomass production of plant communities after controlling for PD. In his comment, Cadotte expressed two concerns about our analyses. One is that we used non-random subsets of experiments, rather than the full data set, for some of our analyses (types 2, 3). We were clear in stating these analyses were based on non-random subsets that were specifically chosen to minimize the SR–PD correlation and avoid problems associated with multicollinearity. We acknowledge that our tests are conservative, a cost of which is that they sacrifice statistical power while, at the same time, minimizing the chance of drawing an incorrect conclusion. But we disagree with Cadotte's suggestion that our use of non-random data subsets led to ‘biased’ conclusions, and demonstrate later in this response that his claim of bias is unsubstantiated. Cadotte's second concern was that our analyses did not account for differences in biomass across studies. This is an important criticism to consider; we made a mistake by not controlling for variation in biomass. To address this issue, Cadotte used mixed models where study was included as a random effect, and ran analyses that standardized biomass among sites. Collectively, these led Cadotte to conclude ‘All analyses strongly support previous literature claims about the value of PD and I further show that: (i) PD provides a more powerful explanation of variation in biomass production than species richness; (ii) PD explains variation in biomass production after controlling for richness; and (iii) the use of data subsets inadvertently biased the conclusions’. We have two concerns with Cadotte's re-analysis. First, Cadotte's approach largely ignores the concerns we raised about multicollinearity. When two or more predictors exhibit a high degree of correlation, each predictor contains little unique information. As a result, it is difficult (if not impossible) to estimate their independent effects using statistical methods like multivariate or partial regression (Dormann et al. 2013). The consequences of multicollinearity include inflated error estimates that can alter conclusions about what predictors are significant or not, as well as unstable parameter estimates that can change in sign and magnitude with minor alterations to analyses (Graham 2003; Zuur, Ieno & Elphick 2010). Multicollinearity is a concern for the data set of Venail et al. (2015) because PD and SR are correlated with r = 0·90. We were concerned about drawing inferences from predictors that have little unique information, which is why we performed analyses that all attempted to hold one of the two predictors constant while examining the impact of the other. In contrast, Cadotte performed model selection using the full data set where the SR–PD correlation was r = 0·90. We remain sceptical of this approach because of the difficulties generating reliable estimates for strongly correlated predictors. A second issue with Cadotte's analyses, which we are guilty of for some analyses in our study, is the assumption that the relationship between biodiversity (PD or SR) and community biomass is linear. Most studies included in the Venail et al. data set have shown that the effect of biodiversity on community biomass is positive, but nonlinear and decelerating. For example, Cardinale et al. (2011) summarized the form of diversity–biomass relationships for 433 experimental manipulations of primary producer richness and concluded ‘Of the studies that have shown a positive effect of producer diversity on producer biomass, 79% were best fit by some form of a positive but decelerating curve (log, power, or M-M functions, Fig. 5A)’. In contrast, only 13% of studies to date are best fit by linear relationships. We reran Cadotte's analyses after accounting for nonlinear relationships and found that most of his conclusions did not hold. Our modified analyses (provided in accompanying R-code) rerun the same analyses of Cadotte, which account for variation in biomass among studies, but using ln-transformed predictors to also account for positive, decelerating relationships. Cadotte's first set of analyses modelled biomass in experimental plots as linear functions of SR and/or PD with study included as a random effect to account for differences in biomass among sites. These produced an AIC of 10 216 and 10 194 for SR and PD, respectively, and an AIC of 10 196 for a model including both SR and PD as predictors. In contrast, the best model in our modified analyses included both ln-transformed SR and PD with an AIC of 10 184. This represents an improved fit to data compared to Cadotte's analyses, and confirms that failure to account for nonlinear relationships led to inferior models. After confirming that relationships between PD, SR and community biomass are better described by nonlinear models, we reran Cadotte's partial regression analyses which found that PD explains a significant fraction of the residual variation in biomass after accounting for effects of SR (F = 4·09, P = 0·04), but SR did not explain residual variation after accounting for effects of PD (F = 0·09, P = 0·77). Using ln-transformed predictors where the SR–PD correlation was lower (r = 0·70), we found that ln(PD) explained 0·05% of the variation unaccounted for by ln(SR) (F = 3·79, P = 0·052, R2 = 0·005). Yet, ln(SR) explained 1·4% of the residual variation in community biomass unaccounted for by ln(PD) (F = 12, P < 0·01, R2 = 0·014). Cadotte also reran our structural equation model (SEM), but used the full data set where the PD–SR correlation was r = 0·90. He accounted for variation among studies by scaling biomass to have a mean = 0 and SD = 1. Cadotte's SEM (reproduced in Fig. 1a) shows that PD explains a significant fraction of variation in scaled biomass and SD through time. In contrast, SR did not explain variation in either. We reran the same SEM on the full data set, but using ln-transformed predictors to account for nonlinear relationships. The modified SEM was a significantly improved fit over the linear version (compare χ2, P-values and AIC for Fig. 1a,b) and led to conclusions that were consistent with those from our original paper (Venail et al. 2015) where we found SR impacts community biomass, but PD does not. In contrast, PD affects the SD of biomass through time, but SR does not. In his final analysis, Cadotte tried to assess whether the five experiments included in our SEM were a ‘biased’ representation of the full set of 16 experiments. He chose 1000 random subsets of five experiments and, for each subset, ran two mixed effects models – one modelling biomass as a function of PD and one modelling biomass as a function of SR. He then calculated the difference in AIC for the two models. If ΔAIC was <0 (>0), this indicated PD (SR) was a better predictor of biomass for that random subset. The frequency distribution of ΔAIC values (Fig. 3 of his comment) is reproduced in Fig. 1c. The mean of this distribution was significantly <0, suggesting PD is a better predictor of biomass than SR in most random subsets of five experiments. In addition, the subset of five experiments used for our SEM was different than the overall distribution, suggesting biased selection. But Cadotte's conclusions about the ‘representativeness’ of the five experiments are overturned when we repeat the same analyses using ln-transformed predictor variables. Indeed, the balance of evidence favoured ln(SR) as the better model (Fig. 1d) with the distribution of ΔAIC values being significantly >0 (mean = +5·64, t = 12·06, P < 0·01). The value of ΔAIC for the subset of five experiments used in our SEM is near the centre of the distribution, indicating it was not a biased subset. So where do we stand in this exchange? Cadotte, Cardinale & Oakley (2008) found that PD was not only a significant predictor of community biomass in grassland biodiversity experiments, it explained ~2% more variation than SR. We (Venail et al. 2015) suggested that synthesis did not control for multicollinearity among predictors. When we (Venail et al. 2015) controlled for multicollinearity (but failed to account for biomass differences among studies), we found PD was not a significant predictor of community biomass or stability, whereas SR was. Cadotte argued in his comment that our new analyses were incorrect because we did not account for variation in biomass among studies, and were biased by our use of data subsets to control for multicollinearity. Cadotte's re-analyses led him to conclude that PD is not only significant, but is again a better predictor of community biomass than SR. We responded by pointing out that multicollinearity continues to be a concern about Cadotte's analyses, and his conclusions do not hold after accounting for nonlinear relationships between biodiversity and ecosystem functioning. Whether using the statistical approaches from our original paper (Venail et al. 2015) or model selection favoured by Cadotte, we are led to two conclusions: (i) either SR or PD can explain most of the variation in community biomass and stability on their own because they share so much information. However, (ii) when we examine their effects after statistically controlling for the other, there is little evidence that PD is a better predictor of ecological function than SR. SR is usually a significant predictor of community biomass and stability after controlling for variation in PD, whereas PD is often (though not always) non-significant after controlling for variation in SR. We would caution against interpreting these results as evidence that PD does not matter for ecosystem functioning. Cadotte is correct that experiments analysed to date have not been explicitly designed to test hypotheses about PD, and therefore, we will need studies that orthogonally manipulate PD and SR to fully resolve their relative importance. On the other hand, given the existing data and analyses, we think it is important that researchers refrain from claiming that phylogenetic diversity is a ‘strong’ predictor of ecosystem functioning, or a ‘better’ predictor than plant richness in grasslands. Such claims are not supported at this time. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
DA - 2015/12//
PY - 2015/12//
DO - 10.1111/1365-2435.12540
VL - 29
IS - 12
SP - 1607-1610
SN - 1365-2435
ER -
TY - JOUR
TI - Structured estimation for the nonparametric Cox model
AU - Bradic, Jelena
AU - Song, Rui
T2 - ELECTRONIC JOURNAL OF STATISTICS
AB - In this paper, we study theoretical properties of the non-parametric Cox proportional hazards model in a high dimensional non-asymptotic setting. We establish the finite sample oracle $l_{2}$ bounds for a general class of group penalties that allow possible hierarchical and overlapping structures. We approximate the log partial likelihood with a quadratic functional and use truncation arguments to reduce the error. Unlike the existing literature, we exemplify differences between bounded and possibly unbounded non-parametric covariate effects. In particular, we show that bounded effects can lead to prediction bounds similar to the simple linear models, whereas unbounded effects can lead to larger prediction bounds. In both situations we do not assume that the true parameter is necessarily sparse. Lastly, we present new theoretical results for hierarchical and smoothed estimation in the non-parametric Cox model. We provide two examples of the proposed general framework: a Cox model with interactions and an ANOVA type Cox model.
DA - 2015///
PY - 2015///
DO - 10.1214/15-ejs1004
VL - 9
IS - 1
SP - 492-534
SN - 1935-7524
ER -
TY - JOUR
TI - Simulation and analysis of a model dinoflagellate predator-prey system
AU - Mazzoleni, M. J.
AU - Antonelli, T.
AU - Coyne, K. J.
AU - Rossi, L. F.
T2 - EUROPEAN PHYSICAL JOURNAL-SPECIAL TOPICS
DA - 2015/12//
PY - 2015/12//
DO - 10.1140/epjst/e2015-50101-x
VL - 224
IS - 17-18
SP - 3257-3270
SN - 1951-6401
ER -
TY - JOUR
TI - Impact of Low-Dose Oral Exposure to Bisphenol A (BPA) on Juvenile and Adult Rat Exploratory and Anxiety Behavior: A CLARITY-BPA Consortium Study
AU - Rebuli, Meghan E.
AU - Camacho, Luisa
AU - Adonay, Maria E.
AU - Reif, David M.
AU - Aylor, David L.
AU - Patisaul, Heather B.
T2 - TOXICOLOGICAL SCIENCES
AB - Bisphenol A (BPA) is a high volume production chemical and has been identified as an endocrine disruptor, prompting concern that developmental exposure could impact brain development and behavior. Rodent and human studies suggest that early life BPA exposure may result in an anxious, hyperactive phenotype but results are conflicting and data from studies using multiple doses below the no-observed-adverse-effect level are limited. To address this, the present studies were conducted as part of the CLARITY-BPA (Consortium Linking Academic and Regulatory Insights on BPA Toxicity) program. The impact of perinatal BPA exposure (2.5, 25, or 2500 µg/kg body weight (bw)/day) on behaviors related to anxiety and exploratory activity was assessed in juvenile (prepubertal) and adult NCTR Sprague-Dawley rats of both sexes. Ethinyl estradiol (0.5 µg/kg bw/day) was used as a reference estrogen. Exposure spanned gestation and lactation with dams gavaged from gestational day 6 until birth and then the offspring gavaged directly through weaning (n = 12/sex/group). Behavioral assessments included open field, elevated plus maze, and zero maze. Anticipated sex differences in behavior were statistically identified or suggested in most cases. No consistent effects of BPA were observed for any endpoint, in either sex, at either age compared to vehicle controls; however, significant differences between BPA-exposed and ethinyl estradiol-exposed groups were identified for some endpoints. Limitations of this study are discussed and include suboptimal statistical power and low concordance across behavioral tasks. These data do not indicate BPA-related effects on anxiety or exploratory activity in these developmentally exposed rats.
DA - 2015/12//
PY - 2015/12//
DO - 10.1093/toxsci/kfv163
VL - 148
IS - 2
SP - 341-354
SN - 1096-0929
KW - bisphenol A
KW - CLARITY
KW - behavior
KW - anxiety
KW - exploratory activity
KW - endocrine disruption
KW - EDC
KW - sexually dimorphic
KW - brain
KW - BPA
KW - plastic
ER -
TY - JOUR
TI - High dimension low sample size asymptotics of robust PCA
AU - Zhou, Yi-Hui
AU - Marron, J. S.
T2 - ELECTRONIC JOURNAL OF STATISTICS
AB - Conventional principal component analysis is highly susceptible to outliers. In particular, a sufficiently outlying single data point, can draw the leading principal component toward itself. In this paper, we study the effects of outliers for high dimension and low sample size data, using asymptotics. The non-robust nature of conventional principal component analysis is verified through inconsistency under multivariate Gaussian assumptions with a single spike in the covariance structure, in the presence of a contaminating outlier. In the same setting, the robust method of spherical principal components is consistent with the population eigenvector for the spike model, even in the presence of contamination.
DA - 2015///
PY - 2015///
DO - 10.1214/15-ejs992
VL - 9
IS - 1
SP - 204-218
SN - 1935-7524
KW - Outlier
KW - robustness
KW - spherical PCA
KW - spike model
ER -
TY - JOUR
TI - Astrocytic tracer dynamics estimated from [1-C-11]-acetate PET measurements
AU - Arnold, A.
AU - Calvetti, D.
AU - Gjedde, A.
AU - Iversen, P.
AU - Somersalo, E.
T2 - Mathematical Medicine and Biology-A Journal of the IMA
DA - 2015///
PY - 2015///
VL - 32
IS - 4
SP - 367-382
ER -
TY - JOUR
TI - The Empirical Distribution of a Large Number of Correlated Normal Variables
AU - Azriel, David
AU - Schwartzman, Armin
T2 - JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
AB - David Azriel & Armin SchwartzmanDavid Azriel is lecturer at the Faculty of Industrial Engineering and Management, Technion - Israel Institute of Technology, Haifa 32000, Israel, and Postdoctoral Research Associate in the Department of Statistics of the Wharton School of the University of Pennsylvania, 3730 Walnut Street, Philadelphia, PA 19104 (E-mail: ). Armin Schwartzman is Associate Professor at the Department of Statistics, North Carolina State University, Raleigh, NC 27695 (E-mail: ). The authors are grateful to Philip Reiss from the Department of Child and Adolescent Psychiatry, New York University School of Medicine, for providing the brain imaging data. This work was partially supported by NIH grant R01-CA157528.
DA - 2015/9//
PY - 2015/9//
DO - 10.1080/01621459.2014.958156
VL - 110
IS - 511
SP - 1217-1228
SN - 1537-274X
KW - Asymptotic approximation
KW - Dependent random variables
KW - Empirical null
KW - Factor analysis
KW - High-dimensional data
KW - Strong correlation
ER -
TY - JOUR
TI - Stretch-Triggered Drug Delivery from Wearable Elastomer Films Containing Therapeutic Depots
AU - Di, Jin
AU - Yao, Shanshan
AU - Ye, Yanqi
AU - Cui, Zheng
AU - Yu, Jicheng
AU - Ghosh, Tushar K.
AU - Zhu, Yong
AU - Gu, Zhen
T2 - ACS NANO
AB - Mechanical force-based stimulus provides a simple and easily accessible manner for spatiotemporally controlled drug delivery. Here we describe a wearable, tensile strain-triggered drug delivery device consisting of a stretchable elastomer and microgel depots containing drug loaded nanoparticles. By applying a tensile strain to the elastomer film, the release of drug from the microdepot is promoted due to the enlarged surface area for diffusion and Poisson's ratio-induced compression on the microdepot. Correspondingly, both sustained drug release by daily body motions and pulsatile release by intentional administration can be conveniently achieved. Our work demonstrated that the tensile strain, applied to the stretchable device, facilitated release of therapeutics from microdepots for anticancer and antibacterial treatments. Moreover, polymeric microneedles were further integrated with the stretch-responsive device for transcutaneous delivery of insulin and regulation of blood glucose levels of chemically induced type 1 diabetic mice.
DA - 2015/9//
PY - 2015/9//
DO - 10.1021/acsnano.5b03975
VL - 9
IS - 9
SP - 9407-9415
SN - 1936-086X
KW - drug delivery
KW - wearable devices
KW - stimuli-responsive
KW - nanoparticles
KW - microdepots
ER -
TY - JOUR
TI - Statistical methods for combining information: Stryker family of vehicles reliability case study
AU - Dickinson, R.M.
AU - Freeman, L.J.
AU - Simpson, B.A.
AU - Wilson, A.G.
T2 - Journal of Quality Technology
AB - Problem: Reliability is an essential element in assessing the operational suitability of Department of Defense weapon systems. Reliability takes a prominent role in both the design and analysis of operational tests. In the current era of reduced budgets and increased reliability requirements, it is challenging to verify reliability requirements in a single test. Furthermore, all available data should be considered in order to ensure evaluations provide the most appropriate analysis of the system's reliability.Approach: This paper describes the benefits of using parametric statistical models to combine information across multiple testing events. Both frequentist and Bayesian inference techniques are employed and they are compared and contrasted to illustrate different statistical methods for combining information. We apply these methods to data collected during the developmental and operational test phases for the Stryker family of vehicles.Results: We show that, when we combine the available information across two test phases for the Stryker family of vehicles, reliability estimates are more accurate and precise than those reported previously using traditional methods that use only operational test data in their reliability assessments.
DA - 2015///
PY - 2015///
DO - 10.1080/00224065.2015.11918142
VL - 47
IS - 4
SP - 400-415
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84976273973&partnerID=MN8TOARS
ER -
TY - JOUR
TI - Rare variant testing across methods and thresholds using the multi-kernel sequence kernel association test (MK-SKAT)
AU - Urrutia, Eugene
AU - Lee, Seunggeun
AU - Maity, Arnab
AU - Zhao, Ni
AU - Shen, Judong
AU - Li, Yun
AU - Wu, Michael C.
T2 - STATISTICS AND ITS INTERFACE
AB - Analysis of rare genetic variants has focused on region-based analysis wherein a subset of the variants within a genomic region is tested for association with a complex trait. Two important practical challenges have emerged. First, it is difficult to choose which test to use. Second, it is unclear which group of variants within a region should be tested. Both depend on the unknown true state of nature. Therefore, we develop the Multi-Kernel SKAT (MK-SKAT) which tests across a range of rare variant tests and groupings. Specifically, we demonstrate that several popular rare variant tests are special cases of the sequence kernel association test which compares pair-wise similarity in trait value to similarity in the rare variant genotypes between subjects as measured through a kernel function. Choosing a particular test is equivalent to choosing a kernel. Similarly, choosing which group of variants to test also reduces to choosing a kernel. Thus, MK-SKAT uses perturbation to test across a range of kernels. Simulations and real data analyses show that our framework controls type I error while maintaining high power across settings: MK-SKAT loses power when compared to the kernel for a particular scenario but has much greater power than poor choices.
DA - 2015///
PY - 2015///
DO - 10.4310/sii.2015.v8.n4.a8
VL - 8
IS - 4
SP - 495-505
SN - 1938-7997
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84945274985&partnerID=MN8TOARS
KW - Rare variants
KW - Perturbation
KW - Sequence kernel association test
KW - Sequencing association studies
ER -
TY - JOUR
TI - Proper Use of Allele-Specific Expression Improves Statistical Power for cis-eQTL Mapping with RNA-Seq Data
AU - Hu, Yi-Juan
AU - Sun, Wei
AU - Tzeng, Jung-Ying
AU - Perou, Charles M.
T2 - JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
AB - Studies of expression quantitative trait loci (eQTLs) offer insight into the molecular mechanisms of loci that were found to be associated with complex diseases and the mechanisms can be classified into cis- and trans-acting regulation. At present, high-throughput RNA sequencing (RNA-seq) is rapidly replacing expression microarrays to assess gene expression abundance. Unlike microarrays that only measure the total expression of each gene, RNA-seq also provides information on allele-specific expression (ASE), which can be used to distinguish cis-eQTLs from trans-eQTLs and, more importantly, enhance cis-eQTL mapping. However, assessing the cis-effect of a candidate eQTL on a gene requires knowledge of the haplotypes connecting the candidate eQTL and the gene, which can not be inferred with certainty. The existing two-stage approach that first phases the candidate eQTL against the gene and then treats the inferred phase as observed in the association analysis tends to attenuate the estimated cis-effect and reduce the power for detecting a cis-eQTL. In this article, we provide a maximum-likelihood framework for cis-eQTL mapping with RNA-seq data. Our approach integrates the inference of haplotypes and the association analysis into a single stage, and is thus unbiased and statistically powerful. We also develop a pipeline for performing a comprehensive scan of all local eQTLs for all genes in the genome by controlling for false discovery rate, and implement the methods in a computationally efficient software program. The advantages of the proposed methods over the existing ones are demonstrated through realistic simulation studies and an application to empirical breast cancer data from The Cancer Genome Atlas project. Supplementary materials for this article are available online.
DA - 2015/9//
PY - 2015/9//
DO - 10.1080/01621459.2015.1038449
VL - 110
IS - 511
SP - 962-974
SN - 1537-274X
KW - ASE
KW - eQTL study
KW - Gene expression
KW - Haplotype
KW - Maximum likelihood
ER -
TY - JOUR
TI - Periconceptional Heat Stress of Holstein Dams Is Associated with Differences in Daughter Milk Production and Composition during Multiple Lactations
AU - Brown, Britni M.
AU - Stallings, Jon W.
AU - Clay, John S.
AU - Rhoads, Michelle L.
T2 - PLOS ONE
AB - Heat stress at the time of conception affects the subsequent milk production of primiparous Holstein cows; however, it is unknown whether these effects are maintained across multiple lactations. Therefore, the objective of the current study was to examine the relationship between periconceptional heat stress and measurements of milk production and composition in cows retained within a herd for multiple lactations. National Dairy Herd Improvement Association data was obtained from Dairy Records Management Systems. Records included milk production data and milk composition data from over 75,000 and 44,000 Holstein cows, respectively, born between 2000 and 2010 in Florida, Georgia, and Texas. Conception dates were calculated by subtracting 276 d from the recorded birth date. Records for cows conceived within the months of June, July, and August were retained as heat stress conceived (HSC) cows; cows conceived within the months of December, January, and February were retained as thermoneutral conceived (TNC) contemporaries. Adjusted 305-d mature equivalent milk, protein percent and fat percent were evaluated with a mixed model ANOVA using SAS. Milk production was significantly affected by periconceptional heat stress. When a significant difference or tendency for a difference was detected between the HSC and TNC cows, the TNC produced more milk in all but one comparison. The advantage in milk production for the TNC cows over the HSC cows ranged from 82 ± 42 to 399 ± 61 kg per lactation. Alterations in fat and protein percentage were variable and most often detected in first lactations (first > second or third). Overall, the most striking result of this study is the consistency of the relationship between HSC and milk production. The nature of this relationship suggests that heat stress at or around the time of conception impairs cow milk yield throughout her lifetime.
DA - 2015/10/23/
PY - 2015/10/23/
DO - 10.1371/journal.pone.0133574
VL - 10
IS - 10
SP -
SN - 1932-6203
ER -
TY - JOUR
TI - Malware Detection Using Nonparametric Bayesian Clustering and Classification Techniques
AU - Kao, Yimin
AU - Reich, Brian
AU - Storlie, Curtis
AU - Anderson, Blake
T2 - TECHNOMETRICS
AB - Computer security requires statistical methods to quickly and accurately flag malicious programs. This article proposes a nonparametric Bayesian approach for classifying programs as benign or malicious and simultaneously clustering malicious programs. The analysis is based on the dynamic trace (DT) of instructions under the first-order Markov assumption. Each row of the trace’s transition matrix is modeled using the Dirichlet process mixture (DPM) model. The DPM model clusters programs within each class (malicious or benign), and produces the posterior probability of being a malware which is used for classification. The novelty of the model is using this clustering algorithm to improve the classification accuracy. The simulation study shows that the DPM model outperforms the elastic net logistic (ENL) regression and the support vector machine (SVM) in classification performance under most of the scenarios, and also outperforms the spectral clustering method for grouping similar malware. In an analysis of real malicious and benign programs, the DPM model gives significantly better classification performance than the ENL model, and competitive results to the SVM. More importantly, the DPM model identifies clusters of programs during the classification procedure which is useful for reverse engineering.
DA - 2015/10/2/
PY - 2015/10/2/
DO - 10.1080/00401706.2014.958916
VL - 57
IS - 4
SP - 535-546
SN - 1537-2723
KW - Classification
KW - Clustering
KW - Dirichlet process mixture
KW - Dynamic trace
ER -
TY - JOUR
TI - IsoDOT Detects Differential RNA-Isoform Expression/Usage With Respect to a Categorical or Continuous Covariate With High Sensitivity and Specificity
AU - Sun, Wei
AU - Liu, Yufeng
AU - Crowley, James J.
AU - Chen, Ting-Huei
AU - Zhou, Hua
AU - Chu, Haitao
AU - Huang, Shunping
AU - Kuan, Pei-Fen
AU - Li, Yuan
AU - Miller, Darla
AU - Shaw, Ginger
AU - Wu, Yichao
AU - Zhabotynsky, Vasyl
AU - McMillan, Leonard
AU - Zou, Fei
AU - Sullivan, Patrick F.
AU - Villena, Fernando Pardo-Manuel
T2 - JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
AB - We have developed a statistical method named IsoDOT to assess differential isoform expression (DIE) and differential isoform usage (DIU) using RNA-seq data. Here isoform usage refers to relative isoform expression given the total expression of the corresponding gene. IsoDOT performs two tasks that cannot be accomplished by existing methods: to test DIE/DIU with respect to a continuous covariate, and to test DIE/DIU for one case versus one control. The latter task is not an uncommon situation in practice, e.g., comparing the paternal and maternal alleles of one individual or comparing tumor and normal samples of one cancer patient. Simulation studies demonstrate the high sensitivity and specificity of IsoDOT. We apply IsoDOT to study the effects of haloperidol treatment on the mouse transcriptome and identify a group of genes whose isoform usages respond to haloperidol treatment.
DA - 2015/9//
PY - 2015/9//
DO - 10.1080/01621459.2015.1040880
VL - 110
IS - 511
SP - 975-986
SN - 1537-274X
KW - Differential isoform expression
KW - Differential isoform usage
KW - Isoform
KW - Penalized regression
KW - RNA-seq
ER -
TY - JOUR
TI - Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis
AU - Corvol, H.
AU - Blackman, S. M.
AU - Boelle, P. Y.
AU - Gallins, P. J.
AU - Pace, R. G.
AU - Stonebraker, J. R.
AU - Accurso, F. J.
AU - Clement, A.
AU - Collaco, J. M.
AU - Dang, H.
AU - Dang, A. T.
AU - Franca, A.
AU - Gong, J. F.
AU - Guillot, L.
AU - Keenan, K.
AU - Li, W. L.
AU - Lin, F.
AU - Patrone, M. V.
T2 - Nature Communications
DA - 2015///
PY - 2015///
VL - 6
ER -
TY - JOUR
TI - Fast translation invariant multiscale image denoising
AU - Li, M.
AU - Ghosal, S.
T2 - IEEE Transactions on Image Processing
DA - 2015///
PY - 2015///
VL - 24
IS - 12
SP - 4876-4887
ER -
TY - JOUR
TI - Computing quality scores and uncertainty for approximate pattern matching in geospatial semantic graphs
AU - Stracuzzi, David J.
AU - Brost, Randy C.
AU - Phillips, Cynthia A.
AU - Robinson, David G.
AU - Wilson, Alyson G.
AU - Woodbridge, Diane M. -K.
T2 - STATISTICAL ANALYSIS AND DATA MINING
AB - Abstract Geospatial semantic graphs provide a robust foundation for representing and analyzing remote sensor data. In particular, they support a variety of pattern search operations that capture the spatial and temporal relationships among the objects and events in the data. However, in the presence of large data corpora, even a carefully constructed search query may return a large number of unintended matches. This work considers the problem of calculating a quality score for each match to the query, given that the underlying data are uncertain. We present a preliminary evaluation of three methods for determining both match quality scores and associated uncertainty bounds, illustrated in the context of an example based on overhead imagery data.
DA - 2015///
PY - 2015///
DO - 10.1002/sam.11294
VL - 8
IS - 5-6
SP - 340-352
SN - 1932-1872
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84944877405&partnerID=MN8TOARS
KW - uncertainty
KW - confidence intervals
KW - statistical models
KW - graphical models
KW - distance metric
KW - image interpretation
KW - graph search
ER -
TY - JOUR
TI - WHY DO SIMPLE ALGORITHMS FOR TRIANGLE ENUMERATION WORK IN THE REAL WORLD?
AU - Berry, Jonathan W.
AU - Fostvedt, Luke A.
AU - Nordman, Daniel J.
AU - Phillips, Cynthia A.
AU - Seshadhri, C.
AU - Wilson, Alyson G.
T2 - INTERNET MATHEMATICS
AB - _Listing all triangles is a fundamental graph operation. Triangles can have important interpretations in real-world graphs, especially social and other interaction networks. Despite the lack of provably efficient (linear, or slightly super linear) worst-case algorithms for this problem, practitioners run simple, efficient heuristics to find all triangles in graphs with millions of vertices. How are these heuristics exploiting the structure of these special graphs to provide major speedups in running time_? _We study one of the most prevalent algorithms used by practitioners. A trivial algorithm enumerates all paths of length 2, and checks if each such path is incident to a triangle. A good heuristic is to enumerate only those paths of length 2 in which the middle vertex has the lowest degree. It is easily implemented and is empirically known to give remarkable speedups over the trivial algorithm_. _We study the behavior of this algorithm over graphs with heavy-tailed degree distributions, a defining feature of real-world graphs. The erased configuration model (ECM) efficiently generates a graph with asymptotically (almost) any desired degree sequence. We show that the expected running time of this algorithm over the distribution of graphs created by the ECM is controlled by the ℓ4/3-norm of the degree sequence. Norms of the degree sequence are a measure of the heaviness of the tail, and it is precisely this feature that allows non trivial speedups of simple triangle enumeration algorithms. As a corollary of our main theorem, we prove expected linear-time performance for degree sequences following a power law with exponent α ≥ 7/3, and non trivial speedup whenever_ α ∈ (2, 3).
DA - 2015/11/2/
PY - 2015/11/2/
DO - 10.1080/15427951.2015.1037030
VL - 11
IS - 6
SP - 555-571
SN - 1944-9488
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84953870563&partnerID=MN8TOARS
ER -
TY - JOUR
TI - SUDS, LID, BMPs, WSUD and more - The evolution and application of terminology surrounding urban drainage
AU - Fletcher, Tim D.
AU - Shuster, William
AU - Hunt, William F.
AU - Ashley, Richard
AU - Butler, David
AU - Arthur, Scott
AU - Trowsdale, Sam
AU - Barraud, Sylvie
AU - Semadeni-Davies, Annette
AU - Bertrand-Krajewski, Jean-Luc
AU - Mikkelsen, Peter Steen
AU - Rivard, Gilles
AU - Uhl, Mathias
AU - Dagenais, Danielle
AU - Viklander, Maria
T2 - URBAN WATER JOURNAL
AB - The management of urban stormwater has become increasingly complex over recent decades. Consequently, terminology describing the principles and practices of urban drainage has become increasingly diverse, increasing the potential for confusion and miscommunication. This paper documents the history, scope, application and underlying principles of terms used in urban drainage and provides recommendations for clear communication of these principles. Terminology evolves locally and thus has an important role in establishing awareness and credibility of new approaches and contains nuanced understandings of the principles that are applied locally to address specific problems. Despite the understandable desire to have a ‘uniform set of terminology’, such a concept is flawed, ignoring the fact that terms reflect locally shared understanding. The local development of terminology thus has an important role in advancing the profession, but authors should facilitate communication between disciplines and between regions of the world, by being explicit and accurate in their application.
DA - 2015/10/3/
PY - 2015/10/3/
DO - 10.1080/1573062x.2014.916314
VL - 12
IS - 7
SP - 525-542
SN - 1744-9006
KW - urban stormwater management
KW - water sensitive urban design (WSUD)
KW - stormwater control measures (SCMs)
KW - terminology
KW - Joint Committee on Urban Drainage (JCUD)
KW - alternative techniques
KW - low impact development (LID)
KW - low impact urban design and development (LIUDD)
KW - urban drainage
KW - integrated urban water management (IUWM)
KW - sustainable urban drainage systems (SUDS)
KW - best management practices (BMPs)
KW - green infrastructure (GI)
KW - source control
ER -
TY - JOUR
TI - QUANTILE REGRESSION FOR MIXED MODELS WITH AN APPLICATION TO EXAMINE BLOOD PRESSURE TRENDS IN CHINA
AU - Smith, Luke B.
AU - Fuentes, Montserrat
AU - Gordon-Larsen, Penny
AU - Reich, Brian J.
T2 - ANNALS OF APPLIED STATISTICS
AB - Cardiometabolic diseases have substantially increased in China in the past 20 years and blood pressure is a primary modifiable risk factor. Using data from the China Health and Nutrition Survey we examine blood pressure trends in China from 1991 to 2009, with a concentration on age cohorts and urbanicity. Very large values of blood pressure are of interest, so we model the conditional quantile functions of systolic and diastolic blood pressure. This allows the covariate effects in the middle of the distribution to vary from those in the upper tail, the focal point of our analysis. We join the distributions of systolic and diastolic blood pressure using a copula, which permits the relationships between the covariates and the two responses to share information and enables probabilistic statements about systolic and diastolic blood pressure jointly. Our copula maintains the marginal distributions of the group quantile effects while accounting for within-subject dependence, enabling inference at the population and subject levels. Our population level regression effects change across quantile level, year, and blood pressure type, providing a rich environment for inference. To our knowledge, this is the first quantile function model to explicitly model within-subject autocorrelation and is the first quantile function approach that simultaneously models multivariate conditional response. We find that the association between high blood pressure and living in an urban area has evolved from positive to negative, with the strongest changes occurring in the upper tail. The increase in urbanization over the last twenty years coupled with the transition from the positive association between urbanization and blood pressure in earlier years to a more uniform association with urbanization suggests increasing blood pressure over time throughout China, even in less urbanized areas. Our methods are available in the R package BSquare.
DA - 2015/9//
PY - 2015/9//
DO - 10.1214/15-aoas841
VL - 9
IS - 3
SP - 1226-1246
SN - 1941-7330
KW - Quantile regression
KW - longitudinal
KW - multivariate
KW - Bayesian
KW - blood pressure
ER -
TY - JOUR
TI - Oviposition responses of Aedes mosquitoes to bacterial isolates from attractive bamboo infusions
AU - Ponnusamy, L.
AU - Schal, C.
AU - Wesson, D. M.
AU - Arellano, C.
AU - Apperson, C. S.
T2 - Parasites & Vectors
DA - 2015///
PY - 2015///
VL - 8
ER -
TY - JOUR
TI - Mitochondrial genome sequences reveal evolutionary relationships of the Phytophthora 1c clade species
AU - Lassiter, Erica S.
AU - Russ, Carsten
AU - Nusbaum, Chad
AU - Zeng, Qiandong
AU - Saville, Amanda C.
AU - Olarte, Rodrigo A.
AU - Carbone, Ignazio
AU - Hu, Chia-Hui
AU - Seguin-Orlando, Andaine
AU - Samaniego, Jose A.
AU - Thorne, Jeffrey L.
AU - Ristaino, Jean B.
T2 - CURRENT GENETICS
AB - Phytophthora infestans is one of the most destructive plant pathogens of potato and tomato globally. The pathogen is closely related to four other Phytophthora species in the 1c clade including P. phaseoli, P. ipomoeae, P. mirabilis and P. andina that are important pathogens of other wild and domesticated hosts. P. andina is an interspecific hybrid between P. infestans and an unknown Phytophthora species. We have sequenced mitochondrial genomes of the sister species of P. infestans and examined the evolutionary relationships within the clade. Phylogenetic analysis indicates that the P. phaseoli mitochondrial lineage is basal within the clade. P. mirabilis and P. ipomoeae are sister lineages and share a common ancestor with the Ic mitochondrial lineage of P. andina. These lineages in turn are sister to the P. infestans and P. andina Ia mitochondrial lineages. The P. andina Ic lineage diverged much earlier than the P. andina Ia mitochondrial lineage and P. infestans. The presence of two mitochondrial lineages in P. andina supports the hybrid nature of this species. The ancestral state of the P. andina Ic lineage in the tree and its occurrence only in the Andean regions of Ecuador, Colombia and Peru suggests that the origin of this species hybrid in nature may occur there.
DA - 2015/11//
PY - 2015/11//
DO - 10.1007/s00294-015-0480-3
VL - 61
IS - 4
SP - 567-577
SN - 1432-0983
KW - Phytophthora 1 c clade
KW - Mitochondria
KW - Late blight
KW - Phylogenetics
ER -
TY - JOUR
TI - Implications of heterogeneous biting exposure and animal hosts on Trypanosomiasis brucei gambiense transmission and control
AU - Stone, C. M.
AU - Chitnis, N.
T2 - PLoS Computational Biology
DA - 2015///
PY - 2015///
VL - 11
IS - 10
ER -
TY - JOUR
TI - Implementation and Maintenance of Floating Treatment Wetlands for Urban Stormwater Management
AU - Borne, Karine E.
AU - Fassman-Beck, Elizabeth A.
AU - Winston, Ryan J.
AU - Hunt, William F.
AU - Tanner, Chris C.
T2 - Journal of Environmental Engineering
AB - The floating treatment wetland (FTW) is an innovative hydroponic device which can be installed on the surface of a stormwater retention pond to improve its pollutant removal efficiency. Limited full-scale experiments have been published, and no design or maintenance guidelines have been developed to date to promote their use. This paper presents implementation and maintenance considerations developed based on the monitoring of three full-scale ponds retrofitted with FTWs. Results suggest that the size and relative surface cover of the FTW, the relative root depth, and the capability of the plants to tolerate periodic anaerobic conditions are crucial factors to promote good removal across a spectrum of pollutants. Special attention to the location and anchorage of the FTW are thought to promote good performance and facilitate FTW maintenance. While zinc and copper sediment concentrations were unlikely to cause undue aquatic impacts after 2 years of operation, more frequent sediment removal will be needed than in conventional retention ponds to maintain adequate storage capacity in the permanent pool because of enhanced sedimentation. Given proper installation and maintenance, FTWs can enhance aesthetic and water quality benefits of stormwater ponds.
DA - 2015/11//
PY - 2015/11//
DO - 10.1061/(ASCE)EE.1943-7870.0000959
VL - 141
IS - 11
SP - 04015030
J2 - J. Environ. Eng.
LA - en
OP -
SN - 0733-9372 1943-7870
UR - http://dx.doi.org/10.1061/(ASCE)EE.1943-7870.0000959
DB - Crossref
KW - Floating treatment wetland
KW - Maintenance
KW - Implementation
KW - Design
KW - Sediment
KW - Plant
KW - Constructed wetland
KW - Retention pond
KW - Stormwater
ER -
TY - JOUR
TI - Controls over native perennial grass exclusion and persistence in California grasslands invaded by annuals
AU - Mordecai, E. A.
AU - Molinari, N. A.
AU - Stahlheber, K. A.
AU - Gross, K.
AU - D'Antonio, C.
T2 - Ecology
AB - Despite obvious impacts of nonnative species in many ecosystems, the long-term outcome of competition between native and exotic species often remains unclear. Demographic models can resolve the outcome of competition between native and exotic species and provide insight into conditions favoring exclusion vs. coexistence. California grasslands are one of the most heavily invaded ecosystems in North America. Although California native perennial bunchgrasses are thought to be restricted to a fraction of their original abundance, the eventual outcome of competition with invasive European annual grasses at a local scale (competitive exclusion, stable persistence, or priority effects) remains unresolved. Here, we used a two-species discrete time population growth model to predict the outcome of competition between exotic annual and native perennial grasses in California, and to determine the demographic traits responsible for the outcome. The model is parameterized with empirical data from several field experiments. We found that, once introduced, annual grasses persist stably with little uncertainty. Although perennial grasses are competitively excluded on average, the most likely range of model predictions also includes stable coexistence with annual grasses. As for many other perennial plants, native bunchgrass population growth is highly sensitive to the survival of adults. Management interventions that improve perennial adult survival are likely to be more effective than those that reduce exotic annual seed production or establishment, reduce competition, or increase perennial seedling establishment. Further empirical data on summer survival of bunchgrass adults and competitive effects of annuals on perennials would most improve model predictions because they contribute most to the uncertainty in the predicted outcome for the perennial grass. This work demonstrates how demographic approaches can clarify the outcome of competition between native and exotic species, identify key targets for future empirical work, and predict the effectiveness of management interventions. Such studies are critical both for understanding the impacts of invasion and for targeting management responses that maximize the benefit to native species.
DA - 2015///
PY - 2015///
DO - 10.1890/14-2023.1
VL - 96
IS - 10
SP - 2643-2652
ER -
TY - JOUR
TI - Assessing habitat use by snapper (Chrysophrys auratus) from baited underwater video data in a coastal marine park
AU - Terres, M. A.
AU - Lawrence, E.
AU - Hosack, G. R.
AU - Haywood, M. D. E.
AU - Babcock, R. C.
T2 - PLoS One
DA - 2015///
PY - 2015///
VL - 10
IS - 8
ER -
TY - JOUR
TI - Adaptive truncated weighting for improving marginal structural model estimation of treatment effects informally censored by subsequent therapy
AU - Bai, Xiaofei
AU - Liu, Jingyi
AU - Li, Li
AU - Faries, Douglas
T2 - PHARMACEUTICAL STATISTICS
AB - Randomized clinical trials are designed to estimate the direct effect of a treatment by randomly assigning patients to receive either treatment or control. However, in some trials, patients who discontinued their initial randomized treatment are allowed to switch to another treatment. Therefore, the direct treatment effect of interest may be confounded by subsequent treatment. Moreover, the decision on whether to initiate a second‐line treatment is typically made based on time‐dependent factors that may be affected by prior treatment history. Due to these time‐dependent confounders, traditional time‐dependent Cox models may produce biased estimators of the direct treatment effect. Marginal structural models (MSMs) have been applied to estimate causal treatment effects even in the presence of time‐dependent confounders. However, the occurrence of extremely large weights can inflate the variance of the MSM estimators. In this article, we proposed a new method for estimating weights in MSMs by adaptively truncating the longitudinal inverse probabilities. This method provides balance in the bias variance trade‐off when large weights are inevitable, without the ad hoc removal of selected observations. We conducted simulation studies to explore the performance of different methods by comparing bias, standard deviation, confidence interval coverage rates, and mean square error under various scenarios. We also applied these methods to a randomized, open‐label, phase III study of patients with nonsquamous non‐small cell lung cancer. Copyright © 2015 John Wiley & Sons, Ltd.
DA - 2015///
PY - 2015///
DO - 10.1002/pst.1719
VL - 14
IS - 6
SP - 448-454
SN - 1539-1612
KW - clinical trial
KW - marginal structural model
KW - subsequent confounding
KW - survival analysis
ER -
TY - JOUR
TI - A new method for detecting associations with rare copy-number variants
AU - Tzeng, J. Y.
AU - Magnusson, P. K. E.
AU - Sullivan, P. F.
AU - Szatkiewicz, J. P.
T2 - PLoS Genetics
DA - 2015///
PY - 2015///
VL - 11
IS - 10
ER -
TY - JOUR
TI - A Multiresolution Approach to Estimating the Value Added by Regional Climate Models
AU - Parker, Ryan J.
AU - Reich, Brian J.
AU - Sain, Stephan R.
T2 - JOURNAL OF CLIMATE
AB - Abstract Climate models have emerged as an essential tool for studying the earth’s climate. Global models are computationally expensive, and so a relatively coarse spatial resolution must be used within the model. This hinders direct application for many impacts studies that require regional and local climate information. A regional model with boundary conditions taken from the global model achieves a finer spatial scale for local analysis. In this paper the authors propose a new method for assessing the value added by these higher-resolution models, and they demonstrate the method within the context of regional climate models (RCMs) from the North American Regional Climate Change Assessment Program (NARCCAP) project. This spectral approach using the discrete cosine transformation (DCT) is based on characterizing the joint relationship between observations, coarser-scale models, and higher-resolution models to identify how the finer scales add value over the coarser output. The joint relationship is computed by estimating the covariance of the data sources at different spatial scales with a Bayesian hierarchical model. Using this model the authors can then estimate the value added by each data source over the others. For the NARCCAP data, they find that the higher-resolution models add value starting with low wavenumbers corresponding to features 550 km apart (or 11 total 50-km grid boxes per cycle) all the way down to higher wavenumbers at 150 km apart (3 grid boxes per cycle).
DA - 2015/11//
PY - 2015/11//
DO - 10.1175/jcli-d-14-00557.1
VL - 28
IS - 22
SP - 8873-8887
SN - 1520-0442
KW - Mathematical and statistical techniques
KW - Bayesian methods
KW - Models and modeling
KW - Climate models
KW - Spectral analysis
KW - models
KW - distribution
ER -
TY - JOUR
TI - local buckley-james estimation for heteroscedastic accelerated failure time model
AU - Pang, L.
AU - Lu, W. B.
AU - Wang, H. J.
T2 - Statistica Sinica
DA - 2015///
PY - 2015///
VL - 25
IS - 3
SP - 863-877
ER -
TY - JOUR
TI - Variability and distribution among sample test results when sampling unprocessed oat lots for ochratoxin A
AU - Whitaker, T. B.
AU - Slate, A. B.
AU - Nowicki, T. W.
AU - Giesbrecht, F. G.
T2 - WORLD MYCOTOXIN JOURNAL
AB - In 2008, Health Canada announced it was considering the establishment of maximum levels for ochratoxin A (OTA) in a number of foods, including unprocessed wheat and oats and their products. The Canada Grains Council and Canadian National Millers Association initiated a study to measure the variability and distribution among sample test results so that scientifically based sampling plans could be designed to meet regulatory and industry requirements. Twenty lots of oats naturally contaminated with OTA were identified and sampled according to a nested experimental protocol where 16-two kg laboratory samples were taken from each lot, two 100 g test portions were taken from each comminuted laboratory sample, and two aliquots of the extract from each test portion were analysed for OTA by LC. The variance associated with each step of the OTA test procedure were found to be a function of OTA concentration and regression equations were developed to predict the functional relationship. When using the above OTA test procedure on an oat lot at 5 μg/kg, the sampling, sample preparation, analytical, and total variances were 11.26, 0.10, 0.13 and 11.49, respectively. The 2 kg sampling step accounted for 98.0% (11.26/11.49) of the total variability. The observed OTA distribution among the 16 OTA sample results was found to be positively skewed and the negative binomial distribution was selected to model the OTA distribution among sample test results. The sampling statistics were incorporated into the FAO Mycotoxin Sampling Tool where operating characteristic curves were calculated to predict the chances of rejecting good lots (seller’s risk) and accepting bad lots (buyer’s risk) for various sampling plan designs.
DA - 2015///
PY - 2015///
DO - 10.3920/wmj2014.1858
VL - 8
IS - 4
SP - 511-524
SN - 1875-0796
KW - sampling plan
KW - maximum level
KW - buyer's risk
KW - seller's risk
KW - OC curve
ER -
TY - JOUR
TI - UNCERTAINTY QUANTIFICATION IN MODELING HIV VIRAL MECHANICS
AU - Banks, H. T.
AU - Baraldi, Robert
AU - Cross, Karissa
AU - Flores, Kevin
AU - Mcchesney, Christina
AU - Poag, Laura
AU - Thorpe, Emma
T2 - MATHEMATICAL BIOSCIENCES AND ENGINEERING
AB - We consider an in-host model for HIV-1 infection dynamics developed and validated with patient data in earlier work [7]. We revisit the earlier model in light of progress over the last several years in understanding HIV-1 progression in humans. We then consider statistical models to describe the data and use these with residual plots in generalized least squares problems to develop accurate descriptions of the proper weights for the data. We use recent parameter subset selection techniques [5,6] to investigate the impact of estimated parameters on the corresponding selection scores. Bootstrapping and asymptotic theory are compared in the context of confidence intervals for the resulting parameter estimates.
DA - 2015/10//
PY - 2015/10//
DO - 10.3934/mbe.2015.12.937
VL - 12
IS - 5
SP - 937-964
SN - 1551-0018
ER -
TY - JOUR
TI - The differential effects of increasing frequency and magnitude of extreme events on coral populations
AU - Fabina, Nicholas S.
AU - Baskett, Marissa L.
AU - Gross, Kevin
T2 - ECOLOGICAL APPLICATIONS
AB - Extreme events, which have profound ecological consequences, are changing in both frequency and magnitude with climate change. Because extreme temperatures induce coral bleaching, we can explore the relative impacts of changes in frequency and magnitude of high temperature events on coral reefs. Here, we combined climate projections and a dynamic population model to determine how changing bleaching regimes influence coral persistence. We additionally explored how coral traits and competition with macroalgae mediate changes in bleaching regimes. Our results predict that severe bleaching events reduce coral persistence more than frequent bleaching. Corals with low adult mortality and high growth rates are successful when bleaching is mild, but bleaching resistance is necessary to persist when bleaching is severe, regardless of frequency. The existence of macroalgae-dominated stable states reduces coral persistence and changes the relative importance of coral traits. Building on previous studies, our results predict that management efforts may need to prioritize protection of "weaker" corals with high adult mortality when bleaching is mild, and protection of "stronger" corals with high bleaching resistance when bleaching is severe. In summary, future reef projections and conservation targets depend on both local bleaching regimes and biodiversity.
DA - 2015/9//
PY - 2015/9//
DO - 10.1890/14-0273.1
VL - 25
IS - 6
SP - 1534-1545
SN - 1939-5582
KW - alternative stable states
KW - climate change
KW - coral bleaching
KW - ecological projection
KW - global sensitivity analysis
KW - population dynamics
KW - random forests
KW - species distribution model
KW - Symbiodinium
ER -
TY - JOUR
TI - Surgically planned versus histologically measured lateral tumor margins for resection of cutaneous and subcutaneous mast cell tumors in dogs: 46 cases (2010-2013)
AU - Risselada, Marije
AU - Mathews, Kyle G.
AU - Griffith, Emily
T2 - JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION
AB - Abstract Objective —To compare preplanned lateral surgical margins and measured lateral histologic margins for cutaneous and subcutaneous mast cell tumor (MCT) resections in dogs. Design —Retrospective case series. Sample —51 biopsy specimens from dogs (n = 46) with MCTs. Procedures —All canine patients that underwent curative-intent surgical resection of cutaneous or subcutaneous MCTs from January 1, 2010, through June 30, 2013, with complete medical records including signalment, body condition score (BCS), surgery report (with measured surgical margins), and histopathology report were included. The surgically measured tumor margins in each quadrant were grouped and compared with the corresponding histologic margins. Specimens from dogs with truncal MCTs and a BCS of 7 to 9 on a scale from 1 to 9 (ie, high) were compared with those of dogs with a BCS of 4 to 6 to evaluate effect of BCS on tissue margins. Results —51 specimens were included. Surgically mapped lateral margins differed significantly from histologically reported margins in all 4 quadrants. The mean histologic margins were 35% to 42% smaller than the surgical margins for the combined 51 specimens. A higher BCS did not significantly influence the magnitude of the decrease in lateral margins measured histologically. No significant difference was found for the magnitude of the differences between any of the 4 lateral margins. Conclusions and Clinical Relevance —Results of this study suggested that surgical and histologic margins may differ significantly for canine cutaneous and subcutaneous MCTs. This may be a result of tissue shrinkage following excision and fixation, extension of the MCT beyond palpable margins, or both. Histologic measurements may significantly underestimate the tumor-free margins in dogs with cutaneous and subcutaneous MCTs. ( J Am Vet Med Assoc 2015;247:184–189)
DA - 2015/7/15/
PY - 2015/7/15/
DO - 10.2460/javma.247.2.184
VL - 247
IS - 2
SP - 184-189
SN - 1943-569X
ER -
TY - JOUR
TI - Special issue on Bayesian nonparametrics
AU - Ghoshal, S.
AU - Kleijn, B.
AU - Vaart, A.
AU - van
AU - Zanten, H.
T2 - Journal of Statistical Planning and Inference
DA - 2015///
PY - 2015///
VL - 166
SP - 1-1
ER -
TY - JOUR
TI - Soils beneath suspended pavements: An opportunity for stormwater control and treatment
AU - Page, Jonathan L.
AU - Winston, Ryan J.
AU - Hunt, William F., III
T2 - ECOLOGICAL ENGINEERING
AB - Trees provide air quality, water quality and aesthetic benefits to urban areas. However, urban soils are frequently compacted to meet the structural stability requirements of pavements and buildings. Suspended pavement systems create an uncompacted soil volume beneath pavements in built environments to provide suitable conditions for tree root growth and structural stability for pavements. Another potential use of the soil–root matrix beneath a suspended pavement includes stormwater management. Two suspended pavement systems were constructed in Wilmington, North Carolina, USA, and runoff was routed through the root–soil matrix for detention and treatment. The two retrofits each contained 21.2 m3 of soil volume with a crape myrtle (Lagerstroemia indica x fauriei) and were nearly identical. An impermeable geomembrane isolated the water quality impacts of the system and an internal water storage (IWS) layer promoted NO2,3-N removal through denitrification. At one retrofit, 80% of runoff over the yearlong monitoring period was treated. For storms that did not generate bypass, significant mitigation of peak discharge (QP) was observed (62%). Pollutant concentrations of TKN, NO2,3-N, TAN, TN, O-PO43−, TP, TSS, Cu, Pb and Zn all decreased significantly at both retrofit sites. Effluent NO2,3-N concentrations between the retrofit sites were not significantly different despite varying organic matter content and a substantial difference in influent NO2,3-N concentrations. Effluent concentrations of TSS, Cu, and Zn were not statistically different between the sites, indicating consistent treatment of particulate and particulate-bound pollutants within the systems. This proof-of-concept study illustrates that the soil–root matrix beneath a suspended pavement system can be used as a stormwater control measure (SCM) to concomitantly achieve water quality, pavement stability and urban forestry goals.
DA - 2015/9//
PY - 2015/9//
DO - 10.1016/j.ecoleng.2015.04.060
VL - 82
SP - 40-48
SN - 1872-6992
KW - Suspended pavement
KW - Silva Cell
KW - Stormwater control measure
KW - Bioretention
KW - Street tree
KW - Urban forest
ER -
TY - JOUR
TI - Repeated count surveys help standardize multi-agency estimates of American Oystercatcher (Haematopus palliatus) abundance
AU - Hostetter, Nathan J.
AU - Gardner, Beth
AU - Schweitzer, Sara H.
AU - Boettcher, Ruth
AU - Wilke, Alexandra L.
AU - Addison, Lindsay
AU - Swilling, William R.
AU - Pollock, Kenneth H.
AU - Simons, Theodore R.
T2 - CONDOR
AB - The extensive breeding range of many shorebird species can make integration of survey data problematic at regional spatial scales. We evaluated the effectiveness of standardized repeated count surveys coordinated across 8 agencies to estimate the abundance of American Oystercatcher (Haematopus palliatus) breeding pairs in the southeastern United States. Breeding season surveys were conducted across coastal North Carolina (90 plots) and the Eastern Shore of Virginia (3 plots). Plots were visited on 1–5 occasions during April–June 2013. N-mixture models were used to estimate abundance and detection probability in relation to survey date, tide stage, plot size, and plot location (coastal bay vs. barrier island). The estimated abundance of oystercatchers in the surveyed area was 1,048 individuals (95% credible interval: 851–1,408) and 470 pairs (384–637), substantially higher than estimates that did not account for detection probability (maximum counts of 674 individuals and 316 pairs). Detection probability was influenced by a quadratic function of survey date, and increased from mid-April (~0.60) to mid-May (~0.80), then remained relatively constant through June. Detection probability was also higher during high tide than during low, rising, or falling tides. Abundance estimates from N-mixture models were validated at 13 plots by exhaustive productivity studies (2–5 surveys wk−1). Intensive productivity studies identified 78 breeding pairs across 13 productivity plots while the N-mixture model abundance estimate was 74 pairs (62–119) using only 1–5 replicated surveys season−1. Our results indicate that standardized replicated count surveys coordinated across multiple agencies and conducted during a relatively short time window (closure assumption) provide tremendous potential to meet both agency-level (e.g., state) and regional-level (e.g., flyway) objectives in large-scale shorebird monitoring programs.
DA - 2015/8//
PY - 2015/8//
DO - 10.1650/condor-14-185.1
VL - 117
IS - 3
SP - 354-363
SN - 1938-5129
KW - American Oystercatcher
KW - detection probability
KW - Haematopus palliatus
KW - population size
KW - N-mixture models
ER -
TY - JOUR
TI - Penalized q-learning for dynamic treatment regimens
AU - Song, R.
AU - Wang, W. W.
AU - Zeng, D. L.
AU - Kosorok, M. R.
T2 - Statistica Sinica
DA - 2015///
PY - 2015///
VL - 25
IS - 3
SP - 901-920
ER -
TY - JOUR
TI - Mitochondrial DNA Fragmentation as a Molecular Tool to Monitor Thermal Processing of Plant-Derived, Low-Acid Foods, and Biomaterials
AU - Caldwell, Jane M.
AU - Perez-Diaz, Ilenys M.
AU - Sandeep, K. P.
AU - Simunovic, Josip
AU - Harris, Keith
AU - Osborne, Jason A.
AU - Hassan, Hosni M.
T2 - JOURNAL OF FOOD SCIENCE
AB - Cycle threshold (Ct) increase, quantifying plant-derived DNA fragmentation, was evaluated for its utility as a time-temperature integrator. This novel approach to monitoring thermal processing of fresh, plant-based foods represents a paradigm shift. Instead of using quantitative polymerase chain reaction (qPCR) to detect pathogens, identify adulterants, or authenticate ingredients, this rapid technique was used to quantify the fragmentation of an intrinsic plant mitochondrial DNA (mtDNA) gene over time-temperature treatments. Universal primers were developed which amplified a mitochondrial gene common to plants (atp1). These consensus primers produced a robust qPCR signal in 10 vegetables, 6 fruits, 3 types of nuts, and a biofuel precursor. Using sweet potato (Ipomoea batatas) puree as a model low-acid product and simple linear regression, Ct value was highly correlated to time-temperature treatment (R(2) = 0.87); the logarithmic reduction (log CFU/mL) of the spore-forming Clostridium botulinum surrogate, Geobacillus stearothermophilus (R(2) = 0.87); and cumulative F-value (min) in a canned retort process (R(2) = 0.88), all comparisons conducted at 121 °C. D121 and z-values were determined for G. stearothermophilus ATCC 7953 and were 2.71 min and 11.0 °C, respectively. D121 and z-values for a 174-bp universal plant amplicon were 11.3 min and 9.17 °C, respectively, for mtDNA from sweet potato puree. We present these data as proof-of-concept for a molecular tool that can be used as a rapid, presumptive method for monitoring thermal processing in low-acid plant products.
DA - 2015/8//
PY - 2015/8//
DO - 10.1111/1750-3841.12937
VL - 80
IS - 8
SP - M1804-M1814
SN - 1750-3841
KW - mitochondrial DNA
KW - quantitative PCR
KW - thermal processing
ER -
TY - JOUR
TI - Marginal Functional Regression Models for Analyzing the Feeding Behavior of Pigs
AU - Gertheiss, Jan
AU - Maier, Verena
AU - Hessel, Engel F.
AU - Staicu, Ana-Maria
T2 - JOURNAL OF AGRICULTURAL BIOLOGICAL AND ENVIRONMENTAL STATISTICS
AB - We observe a group of pigs over a period of about 100 days. Using high frequency radio frequency identification, it is recorded when each pig is feeding, leading to very dense binary functional data for each pig and day. One aim of the data analysis is to find pig-specific feeding profiles showing us the typical feeding pattern of each pig. For modeling the data, we use a marginal functional logistic regression approach, allowing us to model the densely observed binary measurements by assuming an underlying smooth subject-specific profile. The method also allows to incorporate additional covariates such as temperature and humidity that may influence the pigs’ behavior. To account for correlation of measurements, we use robust standard errors and corresponding pointwise confidence intervals. Before analyzing the feeding behavior of pigs, the method employed is evaluated in simulation studies. As our approach is rather general, it may also be applied to other types of generalized functional data with similar characteristics as the pig data.
DA - 2015/9//
PY - 2015/9//
DO - 10.1007/s13253-015-0212-7
VL - 20
IS - 3
SP - 353-370
SN - 1537-2693
KW - Animal husbandry
KW - Binary functional data
KW - Generalized additive models
KW - Penalized splines
KW - Pig fattening
ER -
TY - JOUR
TI - Integrated model of chemical perturbations of a biological pathway using 18 in vitro high-throughput screening assays for the estrogen receptor
AU - Judson, R. S.
AU - Magpantay, F. M.
AU - Chickarmane, V.
AU - Haskell, C.
AU - Tania, N.
AU - Taylor, J.
AU - Xia, M. H.
AU - Huang, R. L.
AU - Rotroff, D. M.
AU - Filer, D. L.
AU - Houck, K. A.
AU - Martin, M. T.
AU - Sipes, N.
AU - Richard, A. M.
AU - Mansouri, K.
AU - Setzer, R. W.
AU - Knudsen, T. B.
T2 - Toxicological Sciences
DA - 2015///
PY - 2015///
VL - 148
IS - 1
SP - 137-154
ER -
TY - JOUR
TI - In vitro screening for population variability in toxicity of pesticide-containing mixtures
AU - Abdo, Nour
AU - Wetmore, Barbara A.
AU - Chappell, Grace A.
AU - Shea, Damian
AU - Wright, Fred A.
AU - Rusyn, Ivan
T2 - ENVIRONMENT INTERNATIONAL
AB - Population-based human in vitro models offer exceptional opportunities for evaluating the potential hazard and mode of action of chemicals, as well as variability in responses to toxic insults among individuals. This study was designed to test the hypothesis that comparative population genomics with efficient in vitro experimental design can be used for evaluation of the potential for hazard, mode of action, and the extent of population variability in responses to chemical mixtures. We selected 146 lymphoblast cell lines from 4 ancestrally and geographically diverse human populations based on the availability of genome sequence and basal RNA-seq data. Cells were exposed to two pesticide mixtures - an environmental surface water sample comprised primarily of organochlorine pesticides and a laboratory-prepared mixture of 36 currently used pesticides - in concentration response and evaluated for cytotoxicity. On average, the two mixtures exhibited a similar range of in vitro cytotoxicity and showed considerable inter-individual variability across screened cell lines. However, when in vitro-to-in vivo extrapolation (IVIVE) coupled with reverse dosimetry was employed to convert the in vitro cytotoxic concentrations to oral equivalent doses and compared to the upper bound of predicted human exposure, we found that a nominally more cytotoxic chlorinated pesticide mixture is expected to have greater margin of safety (more than 5 orders of magnitude) as compared to the current use pesticide mixture (less than 2 orders of magnitude) due primarily to differences in exposure predictions. Multivariate genome-wide association mapping revealed an association between the toxicity of current use pesticide mixture and a polymorphism in rs1947825 in C17orf54. We conclude that a combination of in vitro human population-based cytotoxicity screening followed by dosimetric adjustment and comparative population genomics analyses enables quantitative evaluation of human health hazard from complex environmental mixtures. Additionally, such an approach yields testable hypotheses regarding potential toxicity mechanisms.
DA - 2015/12//
PY - 2015/12//
DO - 10.1016/j.envint.2015.09.012
VL - 85
SP - 147-155
SN - 1873-6750
KW - Pesticide
KW - Mixture
KW - Population
ER -
TY - JOUR
TI - Impact of Location, Cropping History, Tillage, and Chlorpyrifos on Soil Arthropods in Peanut
AU - Cardoza, Yasmin J.
AU - Drake, Wendy L.
AU - Jordan, David L.
AU - Schroeder-Moreno, Michelle S.
AU - Arellano, Consuelo
AU - Brandenburg, Rick L.
T2 - ENVIRONMENTAL ENTOMOLOGY
AB - Demand for agricultural production systems that are both economically viable and environmentally conscious continues to increase. In recent years, reduced tillage systems, and grass and pasture rotations have been investigated to help maintain or improve soil quality, increase crop yield, and decrease labor requirements for production. However, documentation of the effects of reduced tillage, fescue rotation systems as well as other management practices, including pesticides, on pest damage and soil arthropod activity in peanut production for the Mid-Atlantic US region is still limited. Therefore, this project was implemented to assess impacts of fescue-based rotation systems on pests and other soil organisms when compared with cash crop rotation systems over four locations in eastern North Carolina. In addition, the effects of tillage (strip vs. conventional) and soil chlorpyrifos application on pod damage and soil-dwelling organisms were also evaluated. Soil arthropod populations were assessed by deploying pitfall traps containing 50% ethanol in each of the sampled plots. Results from the present study provide evidence that location significantly impacts pest damage and soil arthropod diversity in peanut fields. Cropping history also influenced arthropod diversity, with higher diversity in fescue compared with cash crop fields. Corn rootworm damage to pods was higher at one of our locations (Rocky Mount) compared with all others. Cropping history (fescue vs. cash crop) did not have an effect on rootworm damage, but increased numbers of hymenopterans, acarina, heteropterans, and collembolans in fescue compared with cash crop fields. Interestingly, there was an overall tendency for higher number of soil arthropods in traps placed in chlorpyrifos-treated plots compared with nontreated controls.
DA - 2015/8//
PY - 2015/8//
DO - 10.1093/ee/nvv074
VL - 44
IS - 4
SP - 951-959
SN - 1938-2936
KW - mite
KW - springtail
KW - Diabrotica
KW - Arachis hypogaea
KW - fescue
ER -
TY - JOUR
TI - Genome-wide assessment of recurrent genomic imbalances in canine leukemia identifies evolutionarily conserved regions for subtype differentiation
AU - Roode, Sarah C.
AU - Rotroff, Daniel
AU - Avery, Anne C.
AU - Suter, Steven E.
AU - Bienzle, Dorothee
AU - Schiffman, Joshua D.
AU - Motsinger-Reif, Alison
AU - Breen, Matthew
T2 - CHROMOSOME RESEARCH
DA - 2015/12//
PY - 2015/12//
DO - 10.1007/s10577-015-9475-7
VL - 23
IS - 4
SP - 681-708
SN - 1573-6849
KW - Leukemia
KW - Canine
KW - Chromosome
KW - Comparative genomic hybridization
KW - Comparative genomics
ER -
TY - JOUR
TI - Epigenome-wide association study (EWAS) of BMI, BMI change and waist circumference in African American adults identifies multiple replicated loci
AU - Demerath, E. W.
AU - Guan, W. H.
AU - Grove, M. L.
AU - Aslibekyan, S.
AU - Mendelson, M.
AU - Zhou, Y. H.
AU - Hedman, A. K.
AU - Sandling, J. K.
AU - Li, L. A.
AU - Irvin, M. R.
AU - Zhi, D. G.
AU - Deloukas, P.
AU - Liang, L. M.
AU - Liu, C. Y.
AU - Bressler, J.
AU - Spector, T. D.
AU - North, K.
AU - Li, Y.
T2 - Human Molecular Genetics
DA - 2015///
PY - 2015///
VL - 24
IS - 15
SP - 4464-4479
ER -
TY - JOUR
TI - ConvexLAR: An Extension of Least Angle Regression
AU - Xiao, Wei
AU - Wu, Yichao
AU - Zhou, Hua
T2 - JOURNAL OF COMPUTATIONAL AND GRAPHICAL STATISTICS
AB - The least angle regression (LAR) was proposed by Efron, Hastie, Johnstone and Tibshirani in the year 2004 for continuous model selection in linear regression. It is motivated by a geometric argument and tracks a path along which the predictors enter successively and the active predictors always maintain the same absolute correlation (angle) with the residual vector. Although it gains popularity quickly, its extensions seem rare compared to the penalty methods. In this expository article, we show that the powerful geometric idea of LAR can be generalized in a fruitful way. We propose a ConvexLAR algorithm that works for any convex loss function and naturally extends to group selection and data adaptive variable selection. After simple modification, it also yields new exact path algorithms for certain penalty methods such as a convex loss function with lasso or group lasso penalty. Variable selection in recurrent event and panel count data analysis, Ada-Boost, and Gaussian graphical model is reconsidered from the ConvexLAR angle. Supplementary materials for this article are available online.
DA - 2015/7/3/
PY - 2015/7/3/
DO - 10.1080/10618600.2014.962700
VL - 24
IS - 3
SP - 603-626
SN - 1537-2715
KW - Solution path
KW - Group lasso
KW - Regularization
KW - Ordinary differential equation (ODE)
KW - Lasso
ER -
TY - JOUR
TI - Characterisation of Elastic and Acoustic Properties of an Agar-Based Tissue Mimicking Material
AU - Brewin, M. P.
AU - Birch, M. J.
AU - Mehta, D. J.
AU - Reeves, J. W.
AU - Shaw, S.
AU - Kruse, C.
AU - Whiteman, J. R.
AU - Hu, S.
AU - Kenz, Z. R.
AU - Banks, H. T.
AU - Greenwald, S. E.
T2 - ANNALS OF BIOMEDICAL ENGINEERING
AB - As a first step towards an acoustic localisation device for coronary stenosis to provide a non-invasive means of diagnosing arterial disease, measurements are reported for an agar-based tissue mimicking material (TMM) of the shear wave propagation velocity, attenuation and viscoelastic constants, together with one dimensional quasi-static elastic moduli and Poisson’s ratio. Phase velocity and attenuation coefficients, determined by generating and detecting shear waves piezo-electrically in the range 300 Hz–2 kHz, were 3.2–7.5 ms−1 and 320 dBm−1. Quasi-static Young’s modulus, shear modulus and Poisson’s ratio, obtained by compressive or shear loading of cylindrical specimens were 150–160 kPa; 54–56 kPa and 0.37–0.44. The dynamic Young’s and shear moduli, derived from fitting viscoelastic internal variables by an iterative statistical inverse solver to freely oscillating specimens were 230 and 33 kPa and the corresponding relaxation times, 0.046 and 0.036 s. The results were self-consistent, repeatable and provide baseline data required for the computational modelling of wave propagation in a phantom.
DA - 2015/10//
PY - 2015/10//
DO - 10.1007/s10439-015-1294-7
VL - 43
IS - 10
SP - 2587-2596
SN - 1573-9686
KW - Acoustic properties
KW - Acoustic localisation
KW - Coronary artery
KW - Elastic moduli
KW - Poisson's ratio
KW - Shear modulus
KW - Shear wave
KW - Stenosis
KW - Tissue mimicking material
KW - Viscoelasticity
ER -
TY - JOUR
TI - Camera traps and mark-resight models: The value of ancillary data for evaluating assumptions
AU - Parsons, Arielle W.
AU - Simons, Theodore R.
AU - Pollock, Kenneth H.
AU - Stoskopf, Michael K.
AU - Stocking, Jessica J.
AU - O'connell, Allan F., Jr.
T2 - The Journal of Wildlife Management
AB - ABSTRACT Unbiased estimators of abundance and density are fundamental to the study of animal ecology and critical for making sound management decisions. Capture–recapture models are generally considered the most robust approach for estimating these parameters but rely on a number of assumptions that are often violated but rarely validated. Mark‐resight models, a form of capture–recapture, are well suited for use with noninvasive sampling methods and allow for a number of assumptions to be relaxed. We used ancillary data from continuous video and radio telemetry to evaluate the assumptions of mark‐resight models for abundance estimation on a barrier island raccoon ( Procyon lotor ) population using camera traps. Our island study site was geographically closed, allowing us to estimate real survival and in situ recruitment in addition to population size. We found several sources of bias due to heterogeneity of capture probabilities in our study, including camera placement, animal movement, island physiography, and animal behavior. Almost all sources of heterogeneity could be accounted for using the sophisticated mark‐resight models developed by McClintock et al. (2009 b ) and this model generated estimates similar to a spatially explicit mark‐resight model previously developed for this population during our study. Spatially explicit capture–recapture models have become an important tool in ecology and confer a number of advantages; however, non‐spatial models that account for inherent individual heterogeneity may perform nearly as well, especially where immigration and emigration are limited. Non‐spatial models are computationally less demanding, do not make implicit assumptions related to the isotropy of home ranges, and can provide insights with respect to the biological traits of the local population. © 2015 The Wildlife Society.
DA - 2015/8/13/
PY - 2015/8/13/
DO - 10.1002/JWMG.931
VL - 79
IS - 7
SP - 1163-1172
J2 - Jour. Wild. Mgmt.
LA - en
OP -
SN - 0022-541X
UR - http://dx.doi.org/10.1002/JWMG.931
DB - Crossref
KW - ancillary data
KW - camera traps
KW - detection bias
KW - mark-resight
KW - population estimation
KW - Procyon lotor
KW - raccoon
ER -
TY - JOUR
TI - A Fast Multiple-Kernel Method With Applications to Detect Gene-Environment Interaction
AU - Marceau, Rachel
AU - Lu, Wenbin
AU - Holloway, Shannon
AU - Sale, Michele M.
AU - Worrall, Bradford B.
AU - Williams, Stephen R.
AU - Hsu, Fang-Chi
AU - Tzeng, Jung-Ying
T2 - GENETIC EPIDEMIOLOGY
AB - Kernel machine (KM) models are a powerful tool for exploring associations between sets of genetic variants and complex traits. Although most KM methods use a single kernel function to assess the marginal effect of a variable set, KM analyses involving multiple kernels have become increasingly popular. Multikernel analysis allows researchers to study more complex problems, such as assessing gene-gene or gene-environment interactions, incorporating variance-component based methods for population substructure into rare-variant association testing, and assessing the conditional effects of a variable set adjusting for other variable sets. The KM framework is robust, powerful, and provides efficient dimension reduction for multifactor analyses, but requires the estimation of high dimensional nuisance parameters. Traditional estimation techniques, including regularization and the "expectation-maximization (EM)" algorithm, have a large computational cost and are not scalable to large sample sizes needed for rare variant analysis. Therefore, under the context of gene-environment interaction, we propose a computationally efficient and statistically rigorous "fastKM" algorithm for multikernel analysis that is based on a low-rank approximation to the nuisance effect kernel matrices. Our algorithm is applicable to various trait types (e.g., continuous, binary, and survival traits) and can be implemented using any existing single-kernel analysis software. Through extensive simulation studies, we show that our algorithm has similar performance to an EM-based KM approach for quantitative traits while running much faster. We also apply our method to the Vitamin Intervention for Stroke Prevention (VISP) clinical trial, examining gene-by-vitamin effects on recurrent stroke risk and gene-by-age effects on change in homocysteine level.
DA - 2015/9//
PY - 2015/9//
DO - 10.1002/gepi.21909
VL - 39
IS - 6
SP - 456-468
SN - 1098-2272
KW - multiple-kernel analysis
KW - kernel machine regression
KW - exon level association test
KW - gene-environment interaction
KW - gene-gene interactions
ER -
TY - JOUR
TI - Tree-based methods for individualized treatment regimes
AU - Laber, E. B.
AU - Zhao, Y. Q.
T2 - BIOMETRIKA
AB - Individualized treatment rules recommend treatments on the basis of individual patient characteristics. A high-quality treatment rule can produce better patient outcomes, lower costs and less treatment burden. If a treatment rule learned from data is to be used to inform clinical practice or provide scientific insight, it is crucial that it be interpretable; clinicians may be unwilling to implement models they do not understand, and black-box models may not be useful for guiding future research. The canonical example of an interpretable prediction model is a decision tree. We propose a method for estimating an optimal individualized treatment rule within the class of rules that are representable as decision trees. The class of rules we consider is interpretable but expressive. A novel feature of this problem is that the learning task is unsupervised, as the optimal treatment for each patient is unknown and must be estimated. The proposed method applies to both categorical and continuous treatments and produces favourable marginal mean outcomes in simulation experiments. We illustrate it using data from a study of major depressive disorder.
DA - 2015/9//
PY - 2015/9//
DO - 10.1093/biomet/asv028
VL - 102
IS - 3
SP - 501-514
SN - 1464-3510
KW - Continuous treatment
KW - Exploratory analysis
KW - Personalized medicine
KW - Treatment regime
KW - Tree-based method
ER -
TY - JOUR
TI - SCALING-ROTATION DISTANCE AND INTERPOLATION OF SYMMETRIC POSITIVE-DEFINITE MATRICES
AU - Jung, Sungkyu
AU - Schwartzman, Armin
AU - Groisser, David
T2 - SIAM JOURNAL ON MATRIX ANALYSIS AND APPLICATIONS
AB - We introduce a new geometric framework for the set of symmetric positive-definite (SPD) matrices, aimed to characterize deformations of SPD matrices by individual scaling of eigenvalues and rotation of eigenvectors of the SPD matrices. To characterize the deformation, the eigenvalue-eigenvector decomposition is used to find alternative representations of SPD matrices, and to form a Riemannian manifold so that scaling and rotations of SPD matrices are captured by geodesics on this manifold. The problems of non-unique eigen-decompositions and eigenvalue multiplicities are addressed by finding minimal-length geodesics, which gives rise to a distance and an interpolation method for SPD matrices. Computational procedures to evaluate the minimal scaling--rotation deformations and distances are provided for the most useful cases of $2 \times 2$ and $3 \times 3$ SPD matrices. In the new geometric framework, minimal scaling--rotation curves interpolate eigenvalues at constant logarithmic rate, and eigenvectors at constant angular rate. In the context of diffusion tensor imaging, this results in better behavior of the trace, determinant and fractional anisotropy of interpolated SPD matrices in typical cases.
DA - 2015///
PY - 2015///
DO - 10.1137/140967040
VL - 36
IS - 3
SP - 1180-1201
SN - 1095-7162
KW - symmetric positive-definite matrices
KW - eigen-decomposition
KW - Riemannian distance
KW - geodesics
KW - diffusion tensors
ER -
TY - JOUR
TI - Relaxing the Molecular Clock to Different Degrees for Different Substitution Types
AU - Lee, Hui-Jie
AU - Rodrigue, Nicolas
AU - Thorne, Jeffrey L.
T2 - MOLECULAR BIOLOGY AND EVOLUTION
AB - Rates of molecular evolution can vary over time. Diverse statistical techniques for divergence time estimation have been developed to accommodate this variation. These typically require that all sequence (or codon) positions at a locus change independently of one another. They also generally assume that the rates of different types of nucleotide substitutions vary across a phylogeny in the same way. This permits divergence time estimation procedures to employ an instantaneous rate matrix with relative rates that do not differ among branches. However, previous studies have suggested that some substitution types (e.g., CpG to TpG changes in mammals) are more clock-like than others. As has been previously noted, this is biologically plausible given the mutational mechanism of CpG to TpG changes. Through stochastic mapping of sequence histories from context-independent substitution models, our approach allows for context-dependent nucleotide substitutions to change their relative rates over time. We apply our approach to the analysis of a 0.15 Mb intergenic region from eight primates. In accord with previous findings, we find comparatively little rate variation over time for CpG to TpG substitutions but we find more for other substitution types. We conclude by discussing the limitations and prospects of our approach.
DA - 2015/8//
PY - 2015/8//
DO - 10.1093/molbev/msv099
VL - 32
IS - 8
SP - 1948-1961
SN - 1537-1719
KW - CpG transition rate
KW - context-dependent substitution
KW - relaxed molecular clock
KW - divergence time estimation
ER -
TY - JOUR
TI - Relative Quantification and Higher-Order Modeling of the Plasma Glycan Cancer Burden Ratio in Ovarian Cancer Case-Control Samples
AU - Hecht, Elizabeth S.
AU - Scholl, Elizabeth H.
AU - Walker, S. Hunter
AU - Taylor, Amber D.
AU - Cliby, William A.
AU - Motsinger-Reif, Alison A.
AU - Muddiman, David C.
T2 - JOURNAL OF PROTEOME RESEARCH
AB - An early-stage, population-wide biomarker for ovarian cancer (OVC) is essential to reverse its high mortality rate. Aberrant glycosylation by OVC has been reported, but studies have yet to identify an N-glycan with sufficiently high specificity. We curated a human biorepository of 82 case-control plasma samples, with 27%, 12%, 46%, and 15% falling across stages I-IV, respectively. For relative quantitation, glycans were analyzed by the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) strategy for enhanced electrospray ionization, MS/MS analysis. Sixty-three glycan cancer burden ratios (GBRs), defined as the log10 ratio of the case-control extracted ion chromatogram abundances, were calculated above the limit of detection. The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. After Bonferroni correction, seven N-glycans were identified as significant (p < 0.05), and after false discovery rate correction, an additional four glycans were determined to be significant (p < 0.05), with one borderline (p = 0.05). For all N-glycans, the vectors of the effects from stages II-IV were sequentially reversed, suggesting potential biological changes in OVC morphology or in host response.
DA - 2015/10//
PY - 2015/10//
DO - 10.1021/acs.jproteome.5b00703
VL - 14
IS - 10
SP - 4394-4401
SN - 1535-3907
KW - N-linked glycosylation
KW - INLIGHT
KW - ovarian cancer
KW - relative quantification
KW - cancer biomarker
KW - human plasma
ER -
TY - JOUR
TI - Prediction of human population responses to toxic compounds by a collaborative competition
AU - Eduati, F.
AU - Mangravite, L. M.
AU - Wang, T.
AU - Tang, H.
AU - Bare, J. C.
AU - Huang, R. L.
AU - Norman, T.
AU - Kellen, M.
AU - Menden, M. P.
AU - Yang, J. C.
AU - Zhan, X. W.
AU - Zhong, R.
AU - Xiao, G. H.
AU - Xia, M. H.
AU - Abdo, N.
AU - Kosyk, O.
AU - Friend, S.
AU - Dearry, A.
AU - Simeonov, A.
AU - Tice, R. R.
T2 - Nature Biotechnology
DA - 2015///
PY - 2015///
VL - 33
IS - 9
SP - 933-172
ER -
TY - JOUR
TI - Prediction consistency of forward iterated regression and selection technique
AU - Luo, Shikai
AU - Ghosal, Subhashis
T2 - Statistics & Probability Letters
AB - Recently, Hwang et al. (2009) introduced a penalized forward selection technique for high dimensional linear regression which appears to possess excellent prediction and variable selection properties. In this article, we show that the procedure is prediction consistent.
DA - 2015/12//
PY - 2015/12//
DO - 10.1016/j.spl.2015.08.005
VL - 107
SP - 79-83
J2 - Statistics & Probability Letters
LA - en
OP -
SN - 0167-7152
UR - http://dx.doi.org/10.1016/J.SPL.2015.08.005
DB - Crossref
KW - Forward selection
KW - High dimension
KW - Sparsity
KW - Linear regression
KW - Penalization
KW - Prediction consistency
ER -
TY - JOUR
TI - On Discriminating between GCM Forcing Configurations Using Bayesian Reconstructions of Late-Holocene Temperatures
AU - Tingley, Martin
AU - Craigmile, Peter F.
AU - Haran, Murali
AU - Li, Bo
AU - Mannshardt, Elizabeth
AU - Rajaratnam, Bala
T2 - JOURNAL OF CLIMATE
AB - Abstract Several climate modeling groups have recently generated ensembles of last-millennium climate simulations under different forcing scenarios. These experiments represent an ideal opportunity to establish the baseline feasibility of using proxy-based reconstructions of late-Holocene climate as out-of-calibration tests of the fidelity of the general circulation models used to project future climate. This paper develops a formal statistical model for assessing the agreement between members of an ensemble of climate simulations and the ensemble of possible climate histories produced from a hierarchical Bayesian climate reconstruction. As the internal variabilities of the simulated and reconstructed climate are decoupled from one another, the comparison is between the two latent, or unobserved, forced responses. Comparisons of the spatial average of a 600-yr high northern latitude temperature reconstruction to suites of last-millennium climate simulations from the GISS-E2 and CSIRO models, respectively, suggest that the proxy-based reconstructions are able to discriminate only between the crudest features of the simulations within each ensemble. Although one of the three volcanic forcing scenarios used in the GISS-E2 ensemble results in superior agreement with the reconstruction, no meaningful distinctions can be made between simulations performed with different estimates of solar forcing or land cover changes. In the case of the CSIRO model, sequentially adding orbital, greenhouse gas, solar, and volcanic forcings to the simulations generally improves overall consensus with the reconstruction, though the distinctions are not individually significant.
DA - 2015/10//
PY - 2015/10//
DO - 10.1175/jcli-d-15-0208.1
VL - 28
IS - 20
SP - 8264-8281
SN - 1520-0442
KW - Paleoclimate
KW - Bayesian methods
KW - Model evaluation
KW - performance
ER -
TY - JOUR
TI - Identification of South African bermudagrass germplasm with shade tolerance
AU - Dunne, J. C.
AU - Reynolds, W. C.
AU - Miller, G. L.
AU - Arellano, C.
AU - Brandenburg, R. L.
AU - Schoeman, A.
AU - Yelyerton, F. H.
AU - Milla-Lewis, S. R.
T2 - HortScience
DA - 2015///
PY - 2015///
VL - 50
IS - 10
SP - 1419-1425
ER -
TY - JOUR
TI - Evaluating the role of admixture in cancer therapy via in vitro drug response and multivariate genome-wide associations
AU - Jack, John
AU - Havener, Tammy M.
AU - McLeod, Howard L.
AU - Motsinger-Reif, Alison A.
AU - Foster, Matthew
T2 - PHARMACOGENOMICS
AB - We investigate the role of ethnicity and admixture in drug response across a broad group of chemotherapeutic drugs. Also, we generate hypotheses on the genetic variants driving differential drug response through multivariate genome-wide association studies.Immortalized lymphoblastoid cell lines from 589 individuals (Hispanic or non-Hispanic/Caucasian) were used to investigate dose-response for 28 chemotherapeutic compounds. Univariate and multivariate statistical models were used to elucidate associations between genetic variants and differential drug response as well as the role of ethnicity in drug potency and efficacy.For many drugs, the variability in drug response appears to correlate with self-reported race and estimates of genetic ancestry. Additionally, multivariate genome-wide association analyses offered interesting hypotheses governing these differential responses.
DA - 2015///
PY - 2015///
DO - 10.2217/pgs.15.85
VL - 16
IS - 13
SP - 1451-1463
SN - 1744-8042
KW - admixture
KW - cancer
KW - Caucasian
KW - cytotoxicity
KW - drug
KW - genome-wide association study
KW - GWAS
KW - hispanic
KW - in vitro
KW - lymphoblastoid cell lines
ER -
TY - JOUR
TI - Estimation of distributed parameters in permittivity models of composite dielectric materials using reflectance
AU - Banks, H. T.
AU - Catenacci, J.
AU - Hu, S. H.
T2 - Journal of Inverse and Ill-Posed Problems
DA - 2015///
PY - 2015///
VL - 23
IS - 5
SP - 491-509
ER -
TY - JOUR
TI - Effects of silvicultural treatments on temporal variations of spatial autocorrelation in Eucalyptus plantations in Brazil
AU - Kim, Taek Joo
AU - Bullock, Bronson P.
AU - Stape, Jose L.
T2 - FOREST ECOLOGY AND MANAGEMENT
AB - We examined the change in spatial structures of Eucalyptus plantations across different types of silvicultural treatments over a full rotation. Clonal and seed-origin Eucalyptus plots applied with differing levels of fertilization (high vs. traditional) and irrigation (irrigated vs. non-irrigated) treatments were investigated. Additionally, for the clonal plots, uniform vs. heterogeneous stand structure treatments were created using staggered planting dates. The heterogeneous structure of the clonal plots aimed to mimic the seed-origin plots. Spatial structures were characterized by assessing the spatial autocorrelations of diameters, heights, and biomass. We also applied two distance-based neighborhood structures to look at the degree of change in spatial autocorrelations with different numbers of neighboring trees being defined as neighbors. The results suggest that spatial autocorrelations of diameters, heights, and biomass of Eucalyptus plantations were mostly insignificant at an alpha level of 0.05 over the rotation. However, spatial autocorrelations in most plots after the middle of the rotation were predominantly negative, indicating the occurrence of size differences among neighboring trees. In particular, general declining patterns from positive to negative spatial autocorrelations in diameters and biomass, except for plots with the heterogeneous stand structures, were noted at plots treated with high levels of fertilizer. This suggests that high fertilization may have influenced the realizations of microsite effects in the early stage of stand development. General trends in spatial autocorrelations between the two neighborhood structures considered were mostly similar except for several plots differing in intensities of spatial autocorrelations over the rotation.
DA - 2015/12/15/
PY - 2015/12/15/
DO - 10.1016/j.foreco.2015.09.004
VL - 358
SP - 90-97
SN - 1872-7042
KW - Fertilization
KW - Irrigation
KW - Stand structure
KW - Microsite environment
KW - Competition
KW - Moran's I
ER -
TY - JOUR
TI - Cats are rare where coyotes roam
AU - Kays, Roland
AU - Costello, Robert
AU - Forrester, Tavis
AU - Baker, Megan C.
AU - Parsons, Arielle W.
AU - Kalies, Elizabeth L.
AU - Hess, George
AU - Millspaugh, Joshua J.
AU - McShea, William
T2 - JOURNAL OF MAMMALOGY
AB - Domestic cats (Felis catus) have caused the extinction of many island species and are thought to kill many billions of birds and mammals in the continental United States each year. However, the spatial distribution and abundance of cats and their risk to our protected areas remains unknown. We worked with citizen scientists to survey the mammals at 2,117 sites in 32 protected areas and one urban area across 6 states in the eastern United States using camera traps. We found that most protected areas had high levels of coyote (Canis latrans) activity, but few or no domestic cats. The relative abundance of domestic cats in residential yards, where coyotes were rare, was 300 times higher than in the protected areas. Our spatial models of cat distribution show the amount of coyote activity and housing density are the best predictors of cat activity, and that coyotes and cats overlap the most in small urban forests. Coyotes were nocturnal at all sites, while cats were nocturnal in protected areas, but significantly more diurnal in urban sites. We suggest that the ecological impact of free-ranging cats in the region is concentrated in urban areas or other sites, such as islands, with few coyotes. Our study also shows the value of citizen science for conducting broadscale mammal surveys using photo-vouchered locations that ensure high data quality.
DA - 2015/9/29/
PY - 2015/9/29/
DO - 10.1093/jmammal/gyv100
VL - 96
IS - 5
SP - 981-987
SN - 1545-1542
KW - camera trap
KW - Canis latrans
KW - citizen science
KW - Felis catus
KW - invasive species
KW - protected areas
ER -
TY - JOUR
TI - Assessment of an implant-skin interface scoring system for external skeletal fixation of dogs
AU - McDonald-Lynch, M. B.
AU - Marcellin-Little, D. J.
AU - Roe, S. C.
AU - Lascelles, B. D. X.
AU - Trumpatori, B. J.
AU - Griffith, E. H.
T2 - American Journal of Veterinary Research
AB - Abstract OBJECTIVE To assess intraobserver repeatability and interobserver and in vivo versus photographic agreement of a scoring system for the implant-skin interface (ISI) of external skeletal fixation (ESF). SAMPLE 42 photographs of ISIs from 18 dogs for interobserver agreement and intraobserver repeatability and 27 photographs of ISIs from 6 dogs for in vivo versus photograph agreement. PROCEDURES An ISI inflammation scoring system was developed. It included scales for 6 metrics (erythema, drainage amount, drainage type, swelling, hair loss or lack of hair regrowth, and granulation tissue). Photographs of the ISI of ESF were obtained by use of a standard protocol and evaluated to determine intraobserver repeatability and interobserver agreement (Cronbach α; 4 raters) of the ISI score. Agreement between in vivo and photographic ISI scores (2 raters) and correlation between median scores across metrics were evaluated. RESULTS 42 photographs met the inclusion criteria. Overall intraclass correlation coefficients ranged from 0.922 to 0.975. Interobserver overall Cronbach α ranged from 0.835 to 0.943. For in vivo versus photographic assessment, 27 ISIs in 6 dogs and their photographs were evaluated. The Cronbach α for both raters ranged from 0.614 to 0.938. Overall, the Cronbach α ranged from 0.725 to 0.932. Mean photographic scores were greater than mean in vivo scores for each metric. Pearson correlation coefficients ranged from 0.221 to 0.923. Erythema, swelling, and granulation were correlated with all other metrics. CONCLUSIONS AND CLINICAL RELEVANCE In this study, an ISI scoring system used in this study had high repeatability and agreement and may therefore be considered for use in clinical situations. Photographic scores were not equivalent to in vivo scores and should not be used interchangeably.
DA - 2015///
PY - 2015///
DO - 10.2460/ajvr.76.11.931
VL - 76
IS - 11
SP - 931-938
ER -
TY - JOUR
TI - p-values for the Discrete Scan Statistic through Slack Variables
AU - Martin, D. E. K.
T2 - COMMUNICATIONS IN STATISTICS-SIMULATION AND COMPUTATION
AB - The discrete scan statistic is used in many areas of applied probability and statistics to study local clumping of patterns. Testing based on the statistic requires tail probabilities. Whereas the distribution has been studied extensively, most of the results are approximations, due to the difficulties associated with the computation. Results for exact p-values for the statistic have been given for a binary sequence that is independent or first-order Markovian. We give an algorithm to obtain probabilities for the statistic over multi-state trials that are Markovian of a general order of dependence, and explore the algorithm's usefulness.
DA - 2015///
PY - 2015///
DO - 10.1080/03610918.2013.777457
VL - 44
IS - 9
SP - 2223-2239
SN - 1532-4141
KW - Clustering of patterns
KW - Higher order Markovian trials
KW - Multi-state trials
KW - One-dimensional scan statistic
ER -
TY - JOUR
TI - iqLearn: Interactive Q-Learning in R
AU - Linn, K. A.
AU - Laber, E. B.
AU - Stefanski, L. A.
T2 - Journal of Statistical Software
DA - 2015///
PY - 2015///
VL - 64
IS - 1
ER -
TY - JOUR
TI - The human transcriptome across tissues and individuals
AU - Mele, M.
AU - Ferreira, P. G.
AU - Reverter, F.
AU - DeLuca, D. S.
AU - Monlong, J.
AU - Sammeth, M.
AU - Young, T. R.
AU - Goldmann, J. M.
AU - Pervouchine, D. D.
AU - Sullivan, T. J.
AU - Johnson, R.
AU - Segre, A. V.
AU - Djebali, S.
AU - Niarchou, A.
AU - Wright, F. A.
AU - Lappalainen, T.
AU - Calvo, M.
T2 - Science
DA - 2015///
PY - 2015///
VL - 348
IS - 6235
SP - 660-665
ER -
TY - JOUR
TI - The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans
AU - Ardlie, K. G.
AU - DeLuca, D. S.
AU - Segre, A. V.
AU - Sullivan, T. J.
AU - Young, T. R.
AU - Gelfand, E. T.
AU - Trowbridge, C. A.
AU - Maller, J. B.
AU - Tukiainen, T.
AU - Lek, M.
AU - Ward, L. D.
AU - Kheradpour, P.
AU - Iriarte, B.
AU - Meng, Y.
AU - Palmer, C. D.
AU - Esko, T.
AU - Winckler, W.
T2 - Science
DA - 2015///
PY - 2015///
VL - 348
IS - 6235
SP - 648-660
ER -
TY - JOUR
TI - Stretch, wrap, and relax to smartness
AU - ghosh,
T2 - Science
AB - Carbon nanotubes wrapped around rubber cores create resilient conducting fibers [Also see Report by Liu et al. ]
DA - 2015///
PY - 2015///
DO - 10.1126/science.aac7417
VL - 349
IS - 6246
SP - 382–383
ER -
TY - JOUR
TI - Species richness, but not phylogenetic diversity, influences community biomass production and temporal stability in a re-examination of 16 grassland biodiversity studies
AU - Venail, Patrick
AU - Gross, Kevin
AU - Oakley, Todd H.
AU - Narwani, Anita
AU - Allan, Eric
AU - Flombaum, Pedro
AU - Isbell, Forest
AU - Joshi, Jasmin
AU - Reich, Peter B.
AU - Tilman, David
AU - Ruijven, Jasper
AU - Cardinale, Bradley J.
T2 - FUNCTIONAL ECOLOGY
AB - Summary Hundreds of experiments have now manipulated species richness ( SR ) of various groups of organisms and examined how this aspect of biological diversity influences ecosystem functioning. Ecologists have recently expanded this field to look at whether phylogenetic diversity (PD) among species, often quantified as the sum of branch lengths on a molecular phylogeny leading to all species in a community, also predicts ecological function. Some have hypothesized that phylogenetic divergence should be a superior predictor of ecological function than SR because evolutionary relatedness represents the degree of ecological and functional differentiation among species. But studies to date have provided mixed support for this hypothesis. Here, we reanalyse data from 16 experiments that have manipulated plant SR in grassland ecosystems and examined the impact on above‐ground biomass production over multiple time points. Using a new molecular phylogeny of the plant species used in these experiments, we quantified how the PD of plants impacts average community biomass production as well as the stability of community biomass production through time. Using four complementary analyses, we show that, after statistically controlling for variation in SR , PD (the sum of branches in a molecular phylogenetic tree connecting all species in a community) is neither related to mean community biomass nor to the temporal stability of biomass. These results run counter to past claims. However, after controlling for SR , PD was positively related to variation in community biomass over time due to an increase in the variances of individual species, but this relationship was not strong enough to influence community stability. In contrast to the non‐significant relationships between PD, biomass and stability, our analyses show that SR per se tends to increase the mean biomass production of plant communities, after controlling for PD. The relationship between SR and temporal variation in community biomass was either positive, non‐significant or negative depending on which analysis was used. However, the increases in community biomass with SR , independently of PD, always led to increased stability. These results suggest that PD is no better as a predictor of ecosystem functioning than SR . Synthesis . Our study on grasslands offers a cautionary tale when trying to relate PD to ecosystem functioning suggesting that there may be ecologically important trait and functional variation among species that is not explained by phylogenetic relatedness. Our results fail to support the hypothesis that the conservation of evolutionarily distinct species would be more effective than the conservation of SR as a way to maintain productive and stable communities under changing environmental conditions.
DA - 2015/5//
PY - 2015/5//
DO - 10.1111/1365-2435.12432
VL - 29
IS - 5
SP - 615-626
SN - 1365-2435
KW - biodiversity
KW - community biomass
KW - data synthesis
KW - ecosystem functioning
KW - grasslands
KW - phylogenetic diversity
KW - relatedness
KW - stability
ER -
TY - JOUR
TI - Spatial Variable Selection Methods for Investigating Acute Health Effects of Fine Particulate Matter Components
AU - Vock, Laura F. Boehm
AU - Reich, Brian J.
AU - Fuentes, Montserrat
AU - Dominici, Francesca
T2 - BIOMETRICS
AB - Summary Multi-site time series studies have reported evidence of an association between short term exposure to particulate matter (PM) and adverse health effects, but the effect size varies across the United States. Variability in the effect may partially be due to differing community level exposure and health characteristics, but also due to the chemical composition of PM which is known to vary greatly by location and time. The objective of this article is to identify particularly harmful components of this chemical mixture. Because of the large number of highly-correlated components, we must incorporate some regularization into a statistical model. We assume that, at each spatial location, the regression coefficients come from a mixture model with the flavor of stochastic search variable selection, but utilize a copula to share information about variable inclusion and effect magnitude across locations. The model differs from current spatial variable selection techniques by accommodating both local and global variable selection. The model is used to study the association between fine PM (PM 2.5m) components, measured at 115 counties nationally over the period 2000–2008, and cardiovascular emergency room admissions among Medicare patients.
DA - 2015/3//
PY - 2015/3//
DO - 10.1111/biom.12254
VL - 71
IS - 1
SP - 167-177
SN - 1541-0420
KW - Bayesian modeling
KW - Fine particulate matter
KW - Spatial data
KW - Stochastic search variable selection
ER -
TY - JOUR
TI - Spatial Autocorrelation among Different Levels of Genetic Homogeneity and Spacings in Loblolly Pine
AU - Kim, Taek Joo
AU - Bullock, Bronson P.
AU - McKeand, Steven E.
T2 - FOREST SCIENCE
AB - Spatial structures of differing levels of genetic homogeneity and spacing in loblolly pine stands were evaluated by estimating the spatial autocorrelation at the stand level. Four different levels of genetic homogeneity including clones, full-sib families, half-sib families, and a seed orchard mix were randomized into two spacings (3.0 × 6.1 m, 538 trees/ha; and 1.5 × 6.1 m, 1,077 trees/ha). The detrended stem diameters were assessed using a spatial autocorrelation parameter contained in a simultaneous autoregressive model and a standardized Moran's I statistic for the residuals. The results showed that 12.5% of the plots were positively autocorrelated and 5.0% of the plots were negatively autocorrelated at an α level of 0.10. It was found that spacing had an effect on both significant positive and negative spatial autocorrelations. A majority of positively and negatively autocorrelated plots were located in the wider spacing and closer spacing, respectively. No particular trend in terms of different levels of genetic homogeneity was noted except in one specific clone when planted at a wider spacing. Characterization of the spatial autocorrelation structure between individual trees at the stand level will aid in development of better models to represent on-the-ground stand conditions.
DA - 2015/6//
PY - 2015/6//
DO - 10.5849/forsci.14-034
VL - 61
IS - 3
SP - 438-444
SN - 1938-3738
KW - Pious taeda
KW - genetic homogeneity
KW - clones
KW - stem diameter
KW - interdependence
ER -
TY - JOUR
TI - Scan-stratified case-control sampling for modeling blood-brain barrier integrity in multiple sclerosis
AU - Pomann, Gina-Maria
AU - Sweeney, Elizabeth M.
AU - Reich, Daniel S.
AU - Staicu, Ana-Maria
AU - Shinohara, Russell T.
T2 - STATISTICS IN MEDICINE
AB - Multiple sclerosis (MS) is an immune-mediated neurological disease that causes morbidity and disability. In patients with MS, the accumulation of lesions in the white matter of the brain is associated with disease progression and worse clinical outcomes. Breakdown of the blood-brain barrier in newer lesions is indicative of more active disease-related processes and is a primary outcome considered in clinical trials of treatments for MS. Such abnormalities in active MS lesions are evaluated in vivo using contrast-enhanced structural MRI, during which patients receive an intravenous infusion of a costly magnetic contrast agent. In some instances, the contrast agents can have toxic effects. Recently, local image regression techniques have been shown to have modest performance for assessing the integrity of the blood-brain barrier based on imaging without contrast agents. These models have centered on the problem of cross-sectional classification in which patients are imaged at a single study visit and pre-contrast images are used to predict post-contrast imaging. In this paper, we extend these methods to incorporate historical imaging information, and we find the proposed model to exhibit improved performance. We further develop scan-stratified case-control sampling techniques that reduce the computational burden of local image regression models, while respecting the low proportion of the brain that exhibits abnormal vascular permeability.
DA - 2015/9/10/
PY - 2015/9/10/
DO - 10.1002/sim.6520
VL - 34
IS - 20
SP - 2872-2880
SN - 1097-0258
KW - case-control sampling
KW - logistic regression
KW - magnetic resonance imaging
KW - multiple sclerosis
ER -
TY - JOUR
TI - Retrofitting with innovative stormwater control measures: Hydrologic mitigation of impervious cover in the municipal right-of-way
AU - Page, Jonathan L.
AU - Winston, Ryan J.
AU - Mayes, Dave B.
AU - Perrin, Christy
AU - Hunt, William F., III
T2 - JOURNAL OF HYDROLOGY
AB - Impervious Cover (IC) has been shown to increase runoff volumes, peak discharges and pollutant loads to streams, which leads to degraded water quality and biological integrity. Stormwater Control Measures (SCMs) have been developed to mitigate the hydrologic and water quality impacts of urban areas and IC. This paired watershed study evaluated the impacts of SCM retrofits on hydrology for a small urban drainage area. In February 2012, a bioretention cell (BRC) street retrofit, four permeable pavement parking stalls and a tree filter device were installed to control and treat residential street runoff in Wilmington, North Carolina, USA. In the SCM-Retrofit catchment, 52% of the directly connected impervious area (DCIA) and 69% of the total drainage area was retrofitted for potential hydrologic mitigation. Underlying soils in the study area were urban sands. Peak discharge significantly decreased by 28%, while lag times in the catchment remained unchanged. Runoff depth significantly decreased by 52%. When compared to the control catchment, runoff depths in the SCM-Retrofit catchment were significantly less for events with low hourly rainfall intensities (<2.7 mm/h), but significantly greater for events with high intensities (>7.4 mm/h). During post-retrofit monitoring, runoff thresholds in the SCM-Retrofit and control catchments were 5.2 mm and 3.5 mm, respectively. The SCM-Retrofit runoff coefficient decreased from 0.38 to 0.18 and was substantially less than other runoff coefficients reported in the literature for conventional residential development. This study illustrated how a limited number of SCM retrofits installed within the public right-of-way can mitigate some of the hydrologic impacts of existing residential development.
DA - 2015/8//
PY - 2015/8//
DO - 10.1016/j.jhydrol.2015.04.046
VL - 527
SP - 923-932
SN - 1879-2707
KW - Stormwater control measures
KW - Urban runoff
KW - Impervious cover
KW - DCIA
KW - Right-of-way
KW - Green street
ER -
TY - JOUR
TI - Quantitative tract-based white matter heritability in twin neonates
AU - Lee, Seung Jae
AU - Steiner, Rachel J.
AU - Luo, Shikai
AU - Neale, Michael C.
AU - Styner, Martin
AU - Zhu, Hongtu
AU - Gilmore, John H.
T2 - NEUROIMAGE
AB - Studies in adults indicate that white matter microstructure, assessed with diffusion tensor imaging (DTI), has high heritability. Little is known about genetic and environmental influences on DTI parameters, measured along fiber tracts particularly, in early childhood. In the present study, we report comprehensive heritability data of white matter microstructure fractional anisotropy (FA), radial diffusion (RD), and axial diffusion (AD) along 47 fiber tracts using the quantitative tractography in a large sample of neonatal twins (n=356). We found significant genetic influences in almost all tracts with similar heritabilities for FA, RD, and AD as well as positive relationships between these parameters and heritability. In a single tract analysis, genetic influences along the length of the tract were highly variable. These findings suggest that at birth, there is marked heterogeneity of genetic influences of white matter microstructure within white matter tracts. This study provides a basis for future studies of developmental changes in genetic and environmental influences during early childhood, a period of rapid development that likely plays a major role in individual differences in white matter structure and function.
DA - 2015/5/1/
PY - 2015/5/1/
DO - 10.1016/j.neuroimage.2015.02.021
VL - 111
SP - 123-135
SN - 1095-9572
KW - Genetics
KW - Diffusion tensor imaging (DTI)
KW - Quantitative tractography
KW - Fractional anisotropy
KW - Radial diffusivity
KW - Axial diffusivity
ER -
TY - JOUR
TI - On the residual empirical process based on the ALASSO in high dimensions and its functional oracle property
AU - Chatterjee, A.
AU - Gupta, S.
AU - Lahiri, S. N.
T2 - JOURNAL OF ECONOMETRICS
AB - This paper considers post variable-selection inference in a high dimensional penalized regression model based on the ALASSO method of Zou (2006). It is shown that under suitable sparsity conditions, the residual empirical process based on the ALASSO provides valid inference methodology in very high dimensional regression problems where conventional methods fail. It is also shown that the ALASSO based residual empirical process satisfies a functional oracle property, i.e., in addition to selecting the set of relevant variables with probability tending to one, the ALASSO based residual empirical process converges to the same limiting Gaussian process as the OLS based residual empirical process under the oracle. The functional oracle property is critically exploited to construct asymptotically valid confidence bands for the error distribution function and prediction intervals for unobserved values of the response variable in the high dimensional set up, where traditional non-penalized methods are known to fail. Simulation results are presented illustrating finite sample performance of the proposed methodology.
DA - 2015/6//
PY - 2015/6//
DO - 10.1016/j.jeconom.2015.02.012
VL - 186
IS - 2
SP - 317-324
SN - 1872-6895
KW - Asymptotic uniform linearity
KW - Brownian bridge
KW - Oracle property
KW - Prediction intervals
KW - Regularization
KW - Weak convergence
ER -
TY - JOUR
TI - Molecular Cloning, Functional Characterization, and Evolutionary Analysis of Vitamin D Receptors Isolated from Basal Vertebrates
AU - Kollitz, Erin M.
AU - Zhang, Guozhu
AU - Hawkins, Mary Beth
AU - Whitfield, G. Kerr
AU - Reif, David M.
AU - Kullman, Seth W.
T2 - PLOS ONE
AB - The vertebrate genome is a result of two rapid and successive rounds of whole genome duplication, referred to as 1R and 2R. Furthermore, teleost fish have undergone a third whole genome duplication (3R) specific to their lineage, resulting in the retention of multiple gene paralogs. The more recent 3R event in teleosts provides a unique opportunity to gain insight into how genes evolve through specific evolutionary processes. In this study we compare molecular activities of vitamin D receptors (VDR) from basal species that diverged at key points in vertebrate evolution in order to infer derived and ancestral VDR functions of teleost paralogs. Species include the sea lamprey (Petromyzon marinus), a 1R jawless fish; the little skate (Leucoraja erinacea), a cartilaginous fish that diverged after the 2R event; and the Senegal bichir (Polypterus senegalus), a primitive 2R ray-finned fish. Saturation binding assays and gel mobility shift assays demonstrate high affinity ligand binding and classic DNA binding characteristics of VDR has been conserved across vertebrate evolution. Concentration response curves in transient transfection assays reveal EC50 values in the low nanomolar range, however maximum transactivational efficacy varies significantly between receptor orthologs. Protein-protein interactions were investigated using co-transfection, mammalian 2-hybrid assays, and mutations of coregulator activation domains. We then combined these results with our previous study of VDR paralogs from 3R teleosts into a bioinformatics analysis. Our results suggest that 1, 25D3 acts as a partial agonist in basal species. Furthermore, our bioinformatics analysis suggests that functional differences between VDR orthologs and paralogs are influenced by differential protein interactions with essential coregulator proteins. We speculate that we may be observing a change in the pharmacodynamics relationship between VDR and 1, 25D3 throughout vertebrate evolution that may have been driven by changes in protein-protein interactions between VDR and essential coregulators.
DA - 2015/4/9/
PY - 2015/4/9/
DO - 10.1371/journal.pone.0122853
VL - 10
IS - 4
SP -
SN - 1932-6203
ER -
TY - JOUR
TI - Module-based association analysis for omics data with network structure.
AU - Wang, Z
AU - Maity, A
AU - Hsiao, CK
AU - Voora, D
AU - Kaddurah-Daouk, R
AU - Tzeng, JY
T2 - PLoS ONE
AB - Module-based analysis (MBA) aims to evaluate the effect of a group of biological elements sharing common features, such as SNPs in the same gene or metabolites in the same pathways, and has become an attractive alternative to traditional single bio-element approaches. Because bio-elements regulate and interact with each other as part of network, incorporating network structure information can more precisely model the biological effects, enhance the ability to detect true associations, and facilitate our understanding of the underlying biological mechanisms. How-ever, most MBA methods ignore the network structure information, which depicts the interaction and regulation relationship among basic functional units in biology system. We construct the con-nectivity kernel and the topology kernel to capture the relationship among bio-elements in a mod-ule, and use a kernel machine framework to evaluate the joint effect of bio-elements. Our proposed kernel machine approach directly incorporates network structure so to enhance the study effi-ciency; it can assess interactions among modules, account covariates, and is computational effi-cient. Through simulation studies and real data application, we demonstrate that the proposed network-based methods can have markedly better power than the approaches ignoring network information under a range of scenarios.
DA - 2015///
PY - 2015///
DO - 10.1371/journal.pone.0122309
VL - 10
IS - 3
SP - 0122309
UR - http://europepmc.org/abstract/med/25822417
ER -
TY - JOUR
TI - In vitro evaluation of bursting pressure and intestinal luminal area of three jejunostomy tube placement techniques in dogs
AU - Risselada, Marije
AU - Ellison, Gary W.
AU - Winter, Matthew D.
AU - Giglio, Robson F.
AU - Shih, Andre
AU - Hernandez, Jorge A.
AU - Griffith, Emily
T2 - AMERICAN JOURNAL OF VETERINARY RESEARCH
AB - To compare pursestring, Witzel (seromuscular inversion), and seromuscular incision jejunostomy tube placement techniques in vitro.Jejunal specimens from 10 dogs.Jejunal segments (50 cm) were harvested immediately prior to euthanasia from 10 mixed-breed dogs Specimens were harvested with the orad and aborad ends clamped and stored in saline (0.9% NaCl) solution-soaked towels during instrumentation. Three jejunostomy tubes were placed via 3 techniques (pursestring, Witzel, and seromuscular incision), and 2 double lumen central venous catheters were placed at each intestinal end for luminal filling and leak testing. Intestinal luminal area was measured ultrasonographically with specimens suspended in a warm undyed saline solution bath with the intestinal lumen filled with dyed saline solution (intraluminal pressure, 6 mm Hg). Leak testing was performed by means of infusion of dyed saline solution (4 mL/min) until each jejunostomy site failed. Intestinal luminal area and leakage pressure were compared between the 3 tube placement techniques.The Witzel and seromuscular incision techniques decreased the intestinal luminal area measured at the tube insertion site, albeit nonsignificantly. For the seromuscular incision technique, a significant decrease in intestinal luminal area at the intraluminal site of measurement was found. For 2/30 specimens (1/10 pursestring and 1/10 seromuscular incision), failure occurred at pressures within the range of previously reported peak peristaltic pressure for dogs. Failure occurred at supraphysiologic peristaltic pressures for the remaining 28 specimens, including all 10 specimens for the Witzel technique.In this in vitro study, all specimens for the Witzel technique withstood physiologic peristaltic pressures during leak testing. Both tunneling techniques (Witzel and seromuscular incision) created a decrease in intestinal luminal area. Further investigation, including in vivo testing, is indicated to evaluate the clinical relevance of these findings.
DA - 2015/5//
PY - 2015/5//
DO - 10.2460/ajvr.76.5.467
VL - 76
IS - 5
SP - 467-474
SN - 1943-5681
ER -
TY - CONF
TI - Identification of thermal degradation using probabilistic models in reflectance spectroscopy
AU - Criner, A. K.
AU - Cherry, A. J.
AU - Cooney, A. T.
AU - Katter, T. D.
AU - Banks, H. T.
AU - Hu, Shuhua
AU - Catenacci, Jared
T2 - 41ST ANNUAL REVIEW OF PROGRESS IN QUANTITATIVE NONDESTRUCTIVE EVALUATION: Volume 34
AB - Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter Facebook Reddit LinkedIn Tools Icon Tools Reprints and Permissions Cite Icon Cite Search Site Citation A. K. Criner, A. J. Cherry, A. T. Cooney, T. D. Katter, H. T. Banks, Shuhua Hu, Jared Catenacci; Identification of thermal degradation using probabilistic models in reflectance spectroscopy. AIP Conference Proceedings 31 March 2015; 1650 (1): 1898–1906. https://doi.org/10.1063/1.4914816 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAIP Publishing PortfolioAIP Conference Proceedings Search Advanced Search |Citation Search
C2 - 2015///
C3 -
DA - 2015///
DO - 10.1063/1.4914816
VL - 1650
SP - 1898-1906
PB - AIP Publishing LLC
UR - http://dx.doi.org/10.1063/1.4914816
DB - Crossref
ER -
TY - JOUR
TI - Effective dimension reduction for sparse functional data
AU - Yao, F.
AU - Lei, E.
AU - Wu, Y.
T2 - BIOMETRIKA
AB - We propose a method of effective dimension reduction for functional data, emphasizing the sparse design where one observes only a few noisy and irregular measurements for some or all of the subjects. The proposed method borrows strength across the entire sample and provides a way to characterize the effective dimension reduction space, via functional cumulative slicing. Our theoretical study reveals a bias-variance trade-off associated with the regularizing truncation and decaying structures of the predictor process and the effective dimension reduction space. A simulation study and an application illustrate the superior finite-sample performance of the method.
DA - 2015/6//
PY - 2015/6//
DO - 10.1093/biomet/asv006
VL - 102
IS - 2
SP - 421-437
SN - 1464-3510
KW - Cumulative slicing
KW - Effective dimension reduction
KW - Inverse regression
KW - Sparse functional data
ER -
TY - JOUR
TI - Effect of broiler breeder feeding programme and feeder space change at photostimulation using maize- or wheat-based diets on broiler progeny growth performance and leg health
AU - Eusebio-Balcazar, P.
AU - Oviedo-Rondon, E. O.
AU - Wineland, M. J.
AU - Osborne, J.
AU - Brake, J.
T2 - BRITISH POULTRY SCIENCE
AB - 1. The aim of this study was to evaluate the effects of diet type, maternal feeding programme at 29 weeks of age and breeder feeder space change at photostimulation on broiler progeny performance and leg health at 6 weeks of age.2. Fast-feathering Cobb 500 broiler breeders were fed on either maize- or wheat-based diets that had been formulated to have similar nutrient composition during growing and layer phases. Two feeding programmes, fast or flow, were used from 14 to 29 weeks of age. At 22 weeks, 69 females from each pen were placed in a layer house where feeder space was either similar to that in rearing (6.3 to 6.5 cm/female) or was increased from 6.3 to 8.4 cm/female. Eggs produced at 32 and 44 weeks of age were collected and incubated for two broiler experiments. A total of 16 male and 16 female one-d-old chicks were placed in floor pens in two experiments, respectively, with 6 and 4 replicate pens. Broiler gait scores and leg problem prevalence were evaluated at 6 weeks of age.3. Data were analysed as a 2 × 2 × 2 factorial design with diet type, feeding programme and feeder space change as main factors.4. The wheat diet increased the probability of observing crooked toes in broiler progeny compared to the use of maize, but only when breeders were fed according to the fast feeding programme and given similar feeder space as during rearing.5. Breeders given more feeder space in the laying period produced progeny with more locomotion problems compared with those provided similar feeder space, but only when maize was used and the slow feeding programme was applied to the breeders.6. The maternal feeding programme interacted with other factors to influence progeny leg health, but it did not solely influence walking ability or leg problems of progeny.7. In conclusion, an increased probability of observing walking impairment of broiler progeny was detected when breeders were given greater feeder space at photostimulation rather than no change and fed according to the slow feeding programme using maize diets in breeders and progeny.
DA - 2015/5/4/
PY - 2015/5/4/
DO - 10.1080/00071668.2015.1019830
VL - 56
IS - 3
SP - 345-360
SN - 1466-1799
ER -
TY - JOUR
TI - Distribution of the height of local maxima of Gaussian random fields
AU - Cheng, Dan
AU - Schwartzman, Armin
T2 - EXTREMES
AB - Let {f(t) : t ∈ T} be a smooth Gaussian random field over a parameter space T, where T may be a subset of Euclidean space or, more generally, a Riemannian manifold. We provide a general formula for the distribution of the height of a local maximum [Formula: see text] is a local maximum of f(t)} when f is non-stationary. Moreover, we establish asymptotic approximations for the overshoot distribution of a local maximum [Formula: see text] is a local maximum of f(t) and f(t0) > v} as v → ∞. Assuming further that f is isotropic, we apply techniques from random matrix theory related to the Gaussian orthogonal ensemble to compute such conditional probabilities explicitly when T is Euclidean or a sphere of arbitrary dimension. Such calculations are motivated by the statistical problem of detecting peaks in the presence of smooth Gaussian noise.
DA - 2015/6//
PY - 2015/6//
DO - 10.1007/s10687-014-0211-z
VL - 18
IS - 2
SP - 213-240
SN - 1572-915X
KW - Height
KW - Overshoot
KW - Local maxima
KW - Riemannian manifold
KW - Gaussian orthogonal ensemble
KW - Isotropic field
KW - Euler characteristic
KW - Sphere
ER -
TY - JOUR
TI - Criterion validation testing of clinical metrology instruments for measuring degenerative joint disease associated mobility impairment in cats
AU - Gruen, M. E.
AU - Griffith, E. H.
AU - Thomson, A. E.
AU - Simpson, W.
AU - Lascelles, B. D. X.
T2 - PLoS One
DA - 2015///
PY - 2015///
VL - 10
IS - 7
ER -
TY - JOUR
TI - Comparative cytogenetic characterization of primary canine melanocytic lesions using array CGH and fluorescence in situ hybridization
AU - Poorman, Kelsey
AU - Borst, Luke
AU - Moroff, Scott
AU - Roy, Siddharth
AU - Labelle, Philippe
AU - Motsinger-Reif, Alison
AU - Breen, Matthew
T2 - CHROMOSOME RESEARCH
AB - Melanocytic lesions originating from the oral mucosa or cutaneous epithelium are common in the general dog population, with up to 100,000 diagnoses each year in the USA. Oral melanoma is the most frequent canine neoplasm of the oral cavity, exhibiting a highly aggressive course. Cutaneous melanocytomas occur frequently, but rarely develop into a malignant form. Despite the differential prognosis, it has been assumed that subtypes of melanocytic lesions represent the same disease. To address the relative paucity of information about their genomic status, molecular cytogenetic analysis was performed on the three recognized subtypes of canine melanocytic lesions. Using array comparative genomic hybridization (aCGH) analysis, highly aberrant distinct copy number status across the tumor genome for both of the malignant melanoma subtypes was revealed. The most frequent aberrations included gain of dog chromosome (CFA) 13 and 17 and loss of CFA 22. Melanocytomas possessed fewer genome wide aberrations, yet showed a recurrent gain of CFA 20q15.3–17. A distinctive copy number profile, evident only in oral melanomas, displayed a sigmoidal pattern of copy number loss followed immediately by a gain, around CFA 30q14. Moreover, when assessed by fluorescence in situ hybridization (FISH), copy number aberrations of targeted genes, such as gain of c-MYC (80 % of cases) and loss of CDKN2A (68 % of cases), were observed. This study suggests that in concordance with what is known for human melanomas, canine melanomas of the oral mucosa and cutaneous epithelium are discrete and initiated by different molecular pathways.
DA - 2015/6//
PY - 2015/6//
DO - 10.1007/s10577-014-9444-6
VL - 23
IS - 2
SP - 171-186
SN - 1573-6849
KW - Canine
KW - Oral melanoma
KW - Cytogenetics
KW - Array
KW - Comparative genomic hybridization
ER -
TY - JOUR
TI - Characterizing expected benefits of biomarkers in treatment selection
AU - Huang, Ying
AU - Laber, Eric B.
AU - Janes, Holly
T2 - BIOSTATISTICS
AB - Biomarkers associated with heterogeneity in subject responses to treatment hold potential for treatment selection. In practice, the decision regarding whether to adopt a treatment-selection marker depends on the effect of using the marker on the rate of targeted disease and on the cost associated with treatment. We propose an expected benefit measure that incorporates both effects to quantify a marker's treatment-selection capacity. This measure builds upon an existing decision-theoretic framework, but is expanded to account for the fact that optimal treatment absent marker information varies with the cost of treatment. In addition, we establish upper and lower bounds on the expected benefit for a perfect treatment-selection rule which provides the basis for a standardized expected benefit measure. We develop model-based estimators for these measures in a randomized trial setting and evaluate their asymptotic properties. An adaptive bootstrap confidence interval is proposed for inference in the presence of non-regularity. Alternative estimators robust to risk model misspecification are also investigated. We illustrate our methods using the Diabetes Control and Complications Trial where we evaluate the expected benefit of baseline hemoglobin A1C in selecting diabetes treatment.
DA - 2015/4//
PY - 2015/4//
DO - 10.1093/biostatistics/kxu039
VL - 16
IS - 2
SP - 383-399
SN - 1468-4357
KW - Adaptive bootstrap
KW - Biomarker
KW - Expected benefit
KW - Potential outcomes
KW - Treatment selection
ER -
TY - JOUR
TI - Canine urothelial carcinoma: genomically aberrant and comparatively relevant
AU - Shapiro, S. G.
AU - Raghunath, S.
AU - Williams, C.
AU - Motsinger-Reif, A. A.
AU - Cullen, J. M.
AU - Liu, T.
AU - Albertson, D.
AU - Ruvolo, M.
AU - Bergstrom Lucas, A.
AU - Jin, J.
AU - Knapp, D. W.
AU - Schiffman, J. D.
AU - Breen, M.
T2 - CHROMOSOME RESEARCH
AB - Urothelial carcinoma (UC), also referred to as transitional cell carcinoma (TCC), is the most common bladder malignancy in both human and canine populations. In human UC, numerous studies have demonstrated the prevalence of chromosomal imbalances. Although the histopathology of the disease is similar in both species, studies evaluating the genomic profile of canine UC are lacking, limiting the discovery of key comparative molecular markers associated with driving UC pathogenesis. In the present study, we evaluated 31 primary canine UC biopsies by oligonucleotide array comparative genomic hybridization (oaCGH). Results highlighted the presence of three highly recurrent numerical aberrations: gain of dog chromosome (CFA) 13 and 36 and loss of CFA 19. Regional gains of CFA 13 and 36 were present in 97 % and 84 % of cases, respectively, and losses on CFA 19 were present in 77 % of cases. Fluorescence in situ hybridization (FISH), using targeted bacterial artificial chromosome (BAC) clones and custom Agilent SureFISH probes, was performed to detect and quantify these regions in paraffin-embedded biopsy sections and urine-derived urothelial cells. The data indicate that these three aberrations are potentially diagnostic of UC. Comparison of our canine oaCGH data with that of 285 human cases identified a series of shared copy number aberrations. Using an informatics approach to interrogate the frequency of copy number aberrations across both species, we identified those that had the highest joint probability of association with UC. The most significant joint region contained the gene PABPC1, which should be considered further for its role in UC progression. In addition, cross-species filtering of genome-wide copy number data highlighted several genes as high-profile candidates for further analysis, including CDKN2A, S100A8/9, and LRP1B. We propose that these common aberrations are indicative of an evolutionarily conserved mechanism of pathogenesis and harbor genes key to urothelial neoplasia, warranting investigation for diagnostic, prognostic, and therapeutic applications.
DA - 2015/6//
PY - 2015/6//
DO - 10.1007/s10577-015-9471-y
VL - 23
IS - 2
SP - 311-331
SN - 1573-6849
KW - Canine
KW - Urothelial carcinoma
KW - Transitional cell carcinoma
KW - Cytogenetics
KW - Chromosome aberration
KW - Array comparative genomic hybridization
KW - Comparative oncology
ER -
TY - JOUR
TI - Benefits of Model-based Drug Development: A Rigorous, Planned Case Study
AU - Reeve, Russell
AU - Berry, Seth
AU - Xiao, Wei
AU - Ferguson, Bradley
AU - Thuerk, Marcel
AU - Goetz, Ruediger
T2 - COMMUNICATIONS IN STATISTICS-SIMULATION AND COMPUTATION
AB - Model-based drug development (MBDD) is useful to make better quantitative decisions within drug development. However, rigorous evaluation of the benefits has been scarce in the literature. In this study, we take a completed development program, retrospectively repeat it in a virtual setting using MBDD methodologies, and compare it to the traditional drug development process. The conclusion is that the use of MBDD could have facilitated more efficient use of resources.
DA - 2015///
PY - 2015///
DO - 10.1080/03610918.2013.833232
VL - 44
IS - 9
SP - 2210-2222
SN - 1532-4141
KW - Adaptive trial
KW - Bayesian
KW - Dose response
KW - Model-based drug development
KW - Phase I
KW - Phase II
ER -
TY - JOUR
TI - Automatic structure recovery for additive models
AU - Wu, Yichao
AU - Stefanski, Leonard A.
T2 - BIOMETRIKA
AB - We propose an automatic structure recovery method for additive models, based on a backfitting algorithm coupled with local polynomial smoothing, in conjunction with a new kernel-based variable selection strategy. Our method produces estimates of the set of noise predictors, the sets of predictors that contribute polynomially at different degrees up to a specified degree M, and the set of predictors that contribute beyond polynomially of degree M. We prove consistency of the proposed method, and describe an extension to partially linear models. Finite-sample performance of the method is illustrated via Monte Carlo studies and a real-data example.
DA - 2015/6//
PY - 2015/6//
DO - 10.1093/biomet/asu070
VL - 102
IS - 2
SP - 381-395
SN - 1464-3510
KW - Backfitting
KW - Bandwidth estimation
KW - Kernel
KW - Local polynomial
KW - Measurement-error model selection likelihood
KW - Model selection
KW - Profiling
KW - Smoothing
KW - Variable selection
ER -
TY - JOUR
TI - A FREQUENCY DOMAIN EMPIRICAL LIKELIHOOD METHOD FOR IRREGULARLY SPACED SPATIAL DATA
AU - Bandypadhyay, Soutir
AU - Lahiri, Soumendra N.
AU - Nordman, Daniel J.
T2 - ANNALS OF STATISTICS
AB - This paper develops empirical likelihood methodology for irregularly spaced spatial data in the frequency domain. Unlike the frequency domain empirical likelihood (FDEL) methodology for time series (on a regular grid), the formulation of the spatial FDEL needs special care due to lack of the usual orthogonality properties of the discrete Fourier transform for irregularly spaced data and due to presence of nontrivial bias in the periodogram under different spatial asymptotic structures. A spatial FDEL is formulated in the paper taking into account the effects of these factors. The main results of the paper show that Wilks’ phenomenon holds for a scaled version of the logarithm of the proposed empirical likelihood ratio statistic in the sense that it is asymptotically distribution-free and has a chi-squared limit. As a result, the proposed spatial FDEL method can be used to build nonparametric, asymptotically correct confidence regions and tests for covariance parameters that are defined through spectral estimating equations, for irregularly spaced spatial data. In comparison to the more common studentization approach, a major advantage of our method is that it does not require explicit estimation of the standard error of an estimator, which is itself a very difficult problem as the asymptotic variances of many common estimators depend on intricate interactions among several population quantities, including the spectral density of the spatial process, the spatial sampling density and the spatial asymptotic structure. Results from a numerical study are also reported to illustrate the methodology and its finite sample properties.
DA - 2015/4//
PY - 2015/4//
DO - 10.1214/14-aos1291
VL - 43
IS - 2
SP - 519-545
SN - 0090-5364
KW - Confidence sets
KW - discrete Fourier transform
KW - estimating equations
KW - hypotheses testing
KW - periodogram
KW - spectral moment conditions
KW - stochastic design
KW - variogram
KW - Wilks' theorem
ER -
TY - JOUR
TI - The use of clinical parameters to predict obstructive sleep apnea syndrome severity in children the childhood adenotonsillectomy (CHAT) study randomized clinical trial
AU - Mitchell, R. B.
AU - Garetz, S.
AU - Moore, R. H.
AU - Rosen, C. L.
AU - Marcus, C. L.
AU - Katz, E. S.
AU - Arens, R.
AU - Chervin, R. D.
AU - Paruthi, S.
AU - Amin, R.
AU - Elden, L.
AU - Ellenberg, S. S.
AU - Redline, S.
T2 - Jama Otolaryngology-Head & Neck Surgery
DA - 2015///
PY - 2015///
VL - 141
IS - 2
SP - 130-136
ER -
TY - JOUR
TI - Testing in Microbiome-Profiling Studies with MiRKAT, the Microbiome Regression-Based Kernel Association Test
AU - Zhao, Ni
AU - Chen, Jun
AU - Carroll, Ian M.
AU - Ringel-Kulka, Tamar
AU - Epstein, Michael P.
AU - Zhou, Hua
AU - Zhou, Jin J.
AU - Ringel, Yehuda
AU - Li, Hongzhe
AU - Wu, Michael C.
T2 - AMERICAN JOURNAL OF HUMAN GENETICS
AB - High-throughput sequencing technology has enabled population-based studies of the role of the human microbiome in disease etiology and exposure response. Distance-based analysis is a popular strategy for evaluating the overall association between microbiome diversity and outcome, wherein the phylogenetic distance between individuals' microbiome profiles is computed and tested for association via permutation. Despite their practical popularity, distance-based approaches suffer from important challenges, especially in selecting the best distance and extending the methods to alternative outcomes, such as survival outcomes. We propose the microbiome regression-based kernel association test (MiRKAT), which directly regresses the outcome on the microbiome profiles via the semi-parametric kernel machine regression framework. MiRKAT allows for easy covariate adjustment and extension to alternative outcomes while non-parametrically modeling the microbiome through a kernel that incorporates phylogenetic distance. It uses a variance-component score statistic to test for the association with analytical p value calculation. The model also allows simultaneous examination of multiple distances, alleviating the problem of choosing the best distance. Our simulations demonstrated that MiRKAT provides correctly controlled type I error and adequate power in detecting overall association. "Optimal" MiRKAT, which considers multiple candidate distances, is robust in that it suffers from little power loss in comparison to when the best distance is used and can achieve tremendous power gain in comparison to when a poor distance is chosen. Finally, we applied MiRKAT to real microbiome datasets to show that microbial communities are associated with smoking and with fecal protease levels after confounders are controlled for.
DA - 2015/5/7/
PY - 2015/5/7/
DO - 10.1016/j.ajhg.2015.04.003
VL - 96
IS - 5
SP - 797-807
SN - 1537-6605
ER -
TY - JOUR
TI - Stability of Caribbean coral communities quantified by long-term monitoring and autoregression models
AU - Gross, Kevin
AU - Edmunds, Peter J.
T2 - ECOLOGY
AB - Tropical coral reefs exemplify ecosystems imperiled by environmental change. Anticipating the future of reef ecosystems requires understanding how scleractinian corals respond to the multiple environmental disturbances that threaten their survival. We analyzed the stability of coral reefs at three habitats at different depths along the south shore of St. John, U.S. Virgin Islands, using multivariate autoregression (MAR) models and two decades of monitoring data. We quantified several measures of ecosystem stability, including the magnitude of typical stochastic fluctuations, the rate of recovery following disturbance, and the sensitivity of coral cover to hurricanes and elevated sea temperature. Our results show that, even within a -4 km shore, coral communities in different habitats display different stability properties, and that the stability of each habitat corresponds with the habitat's known synecology. Two Orbicella-dominated habitats are less prone to annual stochastic fluctuations than coral communities in shallower water, but they recover slowly from disturbance, and one habitat has suffered recent losses in scleractinian cover that will not be quickly reversed. In contrast, a shallower, low-coral-cover habitat is subject to greater stochastic fluctuations, but rebounds more quickly from disturbance and is more robust to hurricanes and seawater warming. In some sense, the shallower community is more stable, although the stability arguably arises from having little coral cover left. Our results sharpen understanding of recent changes in coral communities at these habitats, provide a more detailed understanding of how these habitats may change in future environments, and illustrate how MAR models can be used to assess stability of communities founded upon long-lived species.
DA - 2015/7//
PY - 2015/7//
DO - 10.1890/14-0941.1
VL - 96
IS - 7
SP - 1812-1822
SN - 1939-9170
KW - autoregression
KW - coral reefs
KW - global climate change
KW - hurricanes
KW - monitoring
KW - seawater temperature
KW - time-series model
KW - U
KW - S
KW - Virgin Islands
ER -
TY - JOUR
TI - Seasonal prediction of landfalling hurricanes along Eastern Seaboard of the United States
AU - Yan, T.
AU - Pietrafesa, L. J.
AU - Dickey, D. A.
AU - Gayes, P. T.
AU - Bao, S.
T2 - INTERNATIONAL JOURNAL OF CLIMATOLOGY
AB - Statistical models for the seasonal prediction of hurricane strikes on the Eastern Seaboard of the United States (ESUS) are developed with the application of the statistical software (SAS) generalized linear model (GENMOD) to perform a Poisson regression linked by a logarithmic function. Preseason climatic/oceanic signals of the El Nino South Oscillation (ENSO), the Atlantic Meridional Mode (AMM), the Atlantic Multi-decadal Oscillation (AMO), Sahel rainfall (20°–10°N, 20°W–10°E) and the North Atlantic sea surface temperature (SST) across a selected domain, all of which are closely associated with the dominant principal components of the North Atlantic Hurricane Track Density Function (HTDF), are applied as predictors. While using the Poisson regression without dividing the season into differing levels of activity types greatly degrades the model, classification of season types [based on accumulated cyclone energy (ACE)] before using the Poisson regression, can significantly improve the model performance. With this proposed new methodology, landfall counts in hyperactive and above-normal season type years can be predicted with 56.01 and 71.36% skill improvements respectively, compared with merely using climatology.
DA - 2015/7//
PY - 2015/7//
DO - 10.1002/joc.4163
VL - 35
IS - 9
SP - 2647-2653
SN - 1097-0088
KW - North Atlantic hurricanes
KW - landfall
KW - ACE
KW - ENSO
KW - AMM
KW - AMO
KW - Sahel rainfall
KW - North Atlantic SST
KW - Eastern Seaboard of the US
ER -
TY - JOUR
TI - Roles of Solvent Accessibility and Gene Expression in Modeling Protein Sequence Evolution
AU - Wang, Kuangyu
AU - Yu, Shuhui
AU - Ji, Xiang
AU - Lakner, Clemens
AU - Griffing, Alexander
AU - Thorne, Jeffrey L.
T2 - EVOLUTIONARY BIOINFORMATICS
AB - Models of protein evolution tend to ignore functional constraints, although structural constraints are sometimes incorporated. Here we propose a probabilistic framework for codon substitution that evaluates joint effects of relative solvent accessibility (RSA), a structural constraint; and gene expression, a functional constraint. First, we explore the relationship between RSA and codon usage at the genomic scale as well as at the individual gene scale. Motivated by these results, we construct our framework by determining how probable is an amino acid, given RSA and gene expression, and then evaluating the relative probability of observing a codon compared to other synonymous codons. We come to the biologically plausible conclusion that both RSA and gene expression are related to amino acid frequencies, but, among synonymous codons, the relative probability of a particular codon is more closely related to gene expression than RSA. To illustrate the potential applications of our framework, we propose a new codon substitution model. Using this model, we obtain estimates of 2N s, the product of effective population size N, and relative fitness difference of allele s. For a training data set consisting of human proteins with known structures and expression data, 2N s is estimated separately for synonymous and nonsynonymous substitutions in each protein. We then contrast the patterns of synonymous and nonsynonymous 2N s estimates across proteins while also taking gene expression levels of the proteins into account. We conclude that our 2N s estimates are too concentrated around 0, and we discuss potential explanations for this lack of variability.
DA - 2015///
PY - 2015///
DO - 10.4137/ebo.s22911
VL - 11
SP -
SN - 1176-9343
KW - protein evolution
KW - protein structure
KW - gene expression
KW - codon usage
KW - scaled selection coefficient
KW - solvent accessibility
ER -
TY - JOUR
TI - Penalized function-on-function regression
AU - Ivanescu, Andrada E.
AU - Staicu, Ana-Maria
AU - Scheipl, Fabian
AU - Greven, Sonja
T2 - COMPUTATIONAL STATISTICS
AB - A general framework for smooth regression of a functional response on one or multiple functional predictors is proposed. Using the mixed model representation of penalized regression expands the scope of function-on-function regression to many realistic scenarios. In particular, the approach can accommodate a densely or sparsely sampled functional response as well as multiple functional predictors that are observed on the same or different domains than the functional response, on a dense or sparse grid, and with or without noise. It also allows for seamless integration of continuous or categorical covariates and provides approximate confidence intervals as a by-product of the mixed model inference. The proposed methods are accompanied by easy to use and robust software implemented in the pffr function of the R package refund. Methodological developments are general, but were inspired by and applied to a diffusion tensor imaging brain tractography dataset.
DA - 2015/6//
PY - 2015/6//
DO - 10.1007/s00180-014-0548-4
VL - 30
IS - 2
SP - 539-568
SN - 1613-9658
KW - Functional data analysis
KW - Functional regression model
KW - Mixed model
KW - Multiple functional predictors
KW - Penalized splines
KW - Tractography data
ER -
TY - JOUR
TI - Parametrically guided estimation in nonparametric varying coefficient models with quasi-likelihood
AU - Davenport, Clemontina A.
AU - Maity, Arnab
AU - Wu, Yichao
T2 - JOURNAL OF NONPARAMETRIC STATISTICS
AB - Varying coefficient models allow us to generalize standard linear regression models to incorporate complex covariate effects by modeling the regression coefficients as functions of another covariate. For nonparametric varying coefficients, we can borrow the idea of parametrically guided estimation to improve asymptotic bias. In this paper, we develop a guided estimation procedure for the nonparametric varying coefficient models. Asymptotic properties are established for the guided estimators and a method of bandwidth selection via bias-variance tradeoff is proposed. We compare the performance of the guided estimator with that of the unguided estimator via both simulation and real data examples.
DA - 2015/4/3/
PY - 2015/4/3/
DO - 10.1080/10485252.2015.1026903
VL - 27
IS - 2
SP - 195-213
SN - 1029-0311
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84929278394&partnerID=MN8TOARS
KW - nonparametric regression
KW - varying coefficient model
KW - generalised linear models
KW - local polynomial smoothing
KW - parametrically guided estimation
KW - 62G08
KW - 62J12
ER -
TY - JOUR
TI - OPTIMAL DESIGN FOR PARAMETER ESTIMATION IN EEG PROBLEMS IN A 3D MULTILAYERED DOMAIN
AU - Banks, H. T.
AU - Rubio, D.
AU - Saintier, N.
AU - Troparevsky, M. I.
T2 - MATHEMATICAL BIOSCIENCES AND ENGINEERING
AB - The fundamental problem of collecting data in the ``best way'' in order to assure statistically efficient estimation of parameters is known as Optimal Experimental Design. Many inverse problems consist in selecting best parameter values of a given mathematical model based on fits to measured data. These are usually formulated as optimization problems and the accuracy of their solutions depends not only on the chosen optimization scheme but also on the given data. We consider an electromagnetic interrogation problem, specifically one arising in an electroencephalography (EEG) problem, of finding optimal number and locations for sensors for source identification in a 3D unit sphere from data on its boundary. In this effort we compare the use of the classical D-optimal criterion for observation points as opposed to that for a uniform observation mesh. We consider location and best number of sensors and report results based on statistical uncertainty analysis of the resulting estimated parameters.
DA - 2015/8//
PY - 2015/8//
DO - 10.3934/mbe.2015.12.739
VL - 12
IS - 4
SP - 739-760
SN - 1551-0018
KW - Electromagnetic inverse problems
KW - optimal design in 3D EEG analysis
KW - parameter estimation
KW - asymptotic error analysis
ER -
TY - JOUR
TI - Multiple window discrete scan statistic for higher-order Markovian sequences
AU - Coleman, Deidra A.
AU - Martin, Donald E. K.
AU - Reich, Brian J.
T2 - JOURNAL OF APPLIED STATISTICS
AB - Accurate and efficient methods to detect unusual clusters of abnormal activity are needed in many fields such as medicine and business. Often the size of clusters is unknown; hence, multiple (variable) window scan statistics are used to identify clusters using a set of different potential cluster sizes. We give an efficient method to compute the exact distribution of multiple window discrete scan statistics for higher-order, multi-state Markovian sequences. We define a Markov chain to efficiently keep track of probabilities needed to compute p-values for the statistic. The state space of the Markov chain is set up by a criterion developed to identify strings that are associated with observing the specified values of the statistic. Using our algorithm, we identify cases where the available approximations do not perform well. We demonstrate our methods by detecting unusual clusters of made free throw shots by National Basketball Association players during the 2009–2010 regular season.
DA - 2015/8/3/
PY - 2015/8/3/
DO - 10.1080/02664763.2015.1005061
VL - 42
IS - 8
SP - 1690-1705
SN - 1360-0532
KW - variable windows
KW - p-values
KW - one-dimensional scan statistics
KW - 60E05
KW - 60J22
ER -
TY - JOUR
TI - Multilevel quantile function modeling with application to birth outcomes
AU - Smith, Luke B.
AU - Reich, Brian J.
AU - Herring, Amy H.
AU - Langlois, Peter H.
AU - Fuentes, Montserrat
T2 - BIOMETRICS
AB - Infants born preterm or small for gestational age have elevated rates of morbidity and mortality. Using birth certificate records in Texas from 2002 to 2004 and Environmental Protection Agency air pollution estimates, we relate the quantile functions of birth weight and gestational age to ozone exposure and multiple predictors, including parental age, race, and education level. We introduce a semi-parametric Bayesian quantile approach that models the full quantile function rather than just a few quantile levels. Our multilevel quantile function model establishes relationships between birth weight and the predictors separately for each week of gestational age and between gestational age and the predictors separately across Texas Public Health Regions. We permit these relationships to vary nonlinearly across gestational age, spatial domain and quantile level and we unite them in a hierarchical model via a basis expansion on the regression coefficients that preserves interpretability. Very low birth weight is a primary concern, so we leverage extreme value theory to supplement our model in the tail of the distribution. Gestational ages are recorded in completed weeks of gestation (integer-valued), so we present methodology for modeling quantile functions of discrete response data. In a simulation study we show that pooling information across gestational age and quantile level substantially reduces MSE of predictor effects. We find that ozone is negatively associated with the lower tail of gestational age in south Texas and across the distribution of birth weight for high gestational ages. Our methods are available in the R package BSquare.
DA - 2015/6//
PY - 2015/6//
DO - 10.1111/biom.12294
VL - 71
IS - 2
SP - 508-519
SN - 1541-0420
KW - Birth weight
KW - Discrete
KW - Extremes
KW - Gestational Age
KW - Graphics processing units
KW - Ozone
KW - Quantile
ER -
TY - JOUR
TI - Maternal Concern about Child Weight in a Study of Weight-Discordant Siblings
AU - Kral, Tanja V. E.
AU - Moore, Renee H.
AU - Compher, Charlene W.
T2 - PUBLIC HEALTH NURSING
AB - Abstract Objective This study examined concern about child weight in mothers of weight‐discordant siblings and determined the accuracy of maternal self‐report versus measured child height, weight, and corresponding body mass index ( BMI ; kg/m 2 ) z‐score. Design and Sample Discordant sibling design. Forty‐seven mothers of 5‐ to 12‐year‐old, weight‐discordant siblings. Measures Mothers self‐reported their concern about child weight for each child separately and for a subset of children, self‐reported their heights and weights. Siblings' height, weight, waist circumference, and adiposity were measured. Results The majority (83%) of mothers expressed concern about their overweight/obese child's weight and 20% of mothers expressed concern about their normal‐weight child's weight ( p < .001). Difference scores in maternal concern about child weight were positively associated with difference scores in sibling BMI z‐score ( r = 0.42; p = .01) and percent body fat ( r = 0.56; p < .001). For overweight/obese children only, maternal‐reported child heights and weights were significantly lower compared to the measured values ( p < .03). Conclusions One fifth of mothers of weight‐discordant siblings were unconcerned about their overweight/obese child's weight and for overweight/obese children only, mothers tended to underreport children's height and weight. Mothers' concern for their overweight/obese child's weight was greater for sibling pairs who were more discordant in their weight.
DA - 2015///
PY - 2015///
DO - 10.1111/phn.12119
VL - 32
IS - 2
SP - 132-142
SN - 1525-1446
KW - maternal concern about child weight
KW - obesity
KW - weight-discordant siblings
ER -
TY - JOUR
TI - Identifying Greater Sage-Grouse source and sink habitats for conservation planning in an energy development landscape
AU - Kirol, Christopher P.
AU - Beck, Jeffrey L.
AU - Huzurbazar, Snehalata V.
AU - Holloran, Matthew J.
AU - Miller, Scott N.
T2 - ECOLOGICAL APPLICATIONS
AB - Conserving a declining species that is facing many threats, including overlap of its habitats with energy extraction activities, depends upon identifying and prioritizing the value of the habitats that remain. In addition, habitat quality is often compromised when source habitats are lost or fragmented due to anthropogenic development. Our objective was to build an ecological model to classify and map habitat quality in terms of source or sink dynamics for Greater Sage‐Grouse ( Centrocercus urophasianus ) in the Atlantic Rim Project Area (ARPA), a developing coalbed natural gas field in south‐central Wyoming, USA. We used occurrence and survival modeling to evaluate relationships between environmental and anthropogenic variables at multiple spatial scales and for all female summer life stages, including nesting, brood‐rearing, and non‐brooding females. For each life stage, we created resource selection functions (RSFs). We weighted the RSFs and combined them to form a female summer occurrence map. We modeled survival also as a function of spatial variables for nest, brood, and adult female summer survival. Our survival models were mapped as survival probability functions individually and then combined with fixed vital rates in a fitness metric model that, when mapped, predicted habitat productivity (productivity map). Our results demonstrate a suite of environmental and anthropogenic variables at multiple scales that were predictive of occurrence and survival. We created a source–sink map by overlaying our female summer occurrence map and productivity map to predict habitats contributing to population surpluses (source habitats) or deficits (sink habitat) and low‐occurrence habitats on the landscape. The source–sink map predicted that of the Sage‐Grouse habitat within the ARPA, 30% was primary source, 29% was secondary source, 4% was primary sink, 6% was secondary sink, and 31% was low occurrence. Our results provide evidence that energy development and avoidance of energy infrastructure were probably reducing the amount of source habitat within the ARPA landscape. Our source–sink map provides managers with a means of prioritizing habitats for conservation planning based on source and sink dynamics. The spatial identification of high value (i.e., primary source) as well as suboptimal (i.e., primary sink) habitats allows for informed energy development to minimize effects on local wildlife populations.
DA - 2015/6//
PY - 2015/6//
DO - 10.1890/13-1152.1
VL - 25
IS - 4
SP - 968-990
SN - 1939-5582
KW - Atlantic Rim Project Area
KW - Centrocercus urophasianus
KW - energy development
KW - fitness
KW - Greater Sage-Grouse
KW - habitat quality
KW - productivity
KW - resource selection functions
KW - source-sink habitats
KW - south-central Wyoming, USA
KW - survival functions
KW - survival modeling
ER -
TY - JOUR
TI - Identification of homogeneous and heterogeneous variables in pooled cohort studies
AU - Cheng, Xin
AU - Lu, Wenbin
AU - Liu, Mengling
T2 - BIOMETRICS
AB - Summary Pooled analyses integrate data from multiple studies and achieve a larger sample size for enhanced statistical power. When heterogeneity exists in variables’ effects on the outcome across studies, the simple pooling strategy fails to present a fair and complete picture of the effects of heterogeneous variables. Thus, it is important to investigate the homogeneous and heterogeneous structure of variables in pooled studies. In this article, we consider the pooled cohort studies with time-to-event outcomes and propose a penalized Cox partial likelihood approach with adaptively weighted composite penalties on variables’ homogeneous and heterogeneous effects. We show that our method can characterize the variables as having heterogeneous, homogeneous, or null effects, and estimate non-zero effects. The results are readily extended to high-dimensional applications where the number of parameters is larger than the sample size. The proposed selection and estimation procedure can be implemented using the iterative shooting algorithm. We conduct extensive numerical studies to evaluate the performance of our proposed method and demonstrate it using a pooled analysis of gene expression in patients with ovarian cancer.
DA - 2015/6//
PY - 2015/6//
DO - 10.1111/biom.12285
VL - 71
IS - 2
SP - 397-403
SN - 1541-0420
KW - Adaptive group lasso
KW - Cox proportional hazards model
KW - Heterogeneity
KW - Penalized partial likelihood
KW - Pooled analysis
KW - Structure identification
ER -
TY - JOUR
TI - Ecologists need robust survey designs, sampling and analytical methods
AU - Hayward, Matt W.
AU - Boitani, Luigi
AU - Burrows, Neil D.
AU - Funston, Paul J.
AU - Karanth, K. Ullas
AU - MacKenzie, Darryl I.
AU - Pollock, Ken H.
AU - Yarnell, Richard W.
T2 - JOURNAL OF APPLIED ECOLOGY
AB - Summary Research that yields conflicting results rightly causes controversy. Where methodological weaknesses are apparent, there is ready opportunity for discord within the scientific community, which may undermine the entire study. We use the debate about the role of dingoes C anis dingo in conservation in A ustralia as a case study for a phenomenon that is relevant to all applied ecologists, where conflicting results have been published in high‐quality journals and yet the problems with the methods used in these studies have led to significant controversy. To alleviate such controversies, scientists need to use robust methods to ensure that their results are repeatable and defendable. To date, this has not occurred in A ustralia's dingo debate due to the use of unvalidated indices that rely on unsupported assumptions. We highlight the problems that poor methods have caused in this debate. We also reiterate our recommendations for practitioners, statisticians and researchers to work together to develop long‐term, multi‐site experimental research programmes using robust methods to understand the impacts of dingoes on mesopredators. Synthesis and applications . Incorporating robust methods and appropriate experimental designs is needed to ensure that conservation actions are appropriately focused and are supported with robust results. Such actions will go a long way towards resolving the debate about the role of dingoes in conservation in A ustralia, and other, ecological debates.
DA - 2015/4//
PY - 2015/4//
DO - 10.1111/1365-2664.12408
VL - 52
IS - 2
SP - 286-290
SN - 1365-2664
KW - detectability
KW - dingo debate
KW - ecological methods
KW - indices
KW - intraguild interactions
KW - occupancy modelling
KW - predator interactions
KW - robust survey methods
KW - scientific debates
ER -
TY - JOUR
TI - Carbon nanotube sheet electrodes for anisotropic actuation of dielectric elastomers
AU - Cakmak, Enes
AU - Fang, Xiaomeng
AU - Yildiz, Ozkan
AU - Bradford, Philip D.
AU - Ghosh, Tushar K.
T2 - CARBON
AB - The performance of dielectric electroactive polymer (D-EAP) based actuators depends critically on the electrode characteristics. Among the most challenging issues in the application of D-EAPs is the device-level complexity in producing sufficient directional actuation at acceptably low electric fields. In this work, a simple carbon nanotube (CNT) based electrode for D-EAP actuators is demonstrated that vastly improves directional strain response originating from the mechanical anisotropy of the electrode material. In this novel approach, highly aligned carbon nanotube (CNT) sheet electrodes are applied on acrylate adhesive films show high directed linear actuation strain of greater than 40% at a relatively low electric field (100 V μm−1). The fiber-oriented CNT sheet applied around the D-EAP film, exhibits strong interaction between CNT fibers in the electrode and the D-EAP film to produce a robust conductive-nanolayer at the interface, on actuation cycling. The design paradigm provides a great potential for the fabrication of soft linear actuators.
DA - 2015/8//
PY - 2015/8//
DO - 10.1016/j.carbon.2015.03.011
VL - 89
SP - 113-120
SN - 1873-3891
ER -
TY - JOUR
TI - Bayesian structure learning in graphical models
AU - Banerjee, Sayantan
AU - Ghosal, Subhashis
T2 - Journal of Multivariate Analysis
AB - We consider the problem of estimating a sparse precision matrix of a multivariate Gaussian distribution, where the dimension p may be large. Gaussian graphical models provide an important tool in describing conditional independence through presence or absence of edges in the underlying graph. A popular non-Bayesian method of estimating a graphical structure is given by the graphical lasso. In this paper, we consider a Bayesian approach to the problem. We use priors which put a mixture of a point mass at zero and certain absolutely continuous distribution on off-diagonal elements of the precision matrix. Hence the resulting posterior distribution can be used for graphical structure learning. The posterior convergence rate of the precision matrix is obtained and is shown to match the oracle rate. The posterior distribution on the model space is extremely cumbersome to compute using the commonly used reversible jump Markov chain Monte Carlo methods. However, the posterior mode in each graph can be easily identified as the graphical lasso restricted to each model. We propose a fast computational method for approximating the posterior probabilities of various graphs using the Laplace approximation approach by expanding the posterior density around the posterior mode. We also provide estimates of the accuracy in the approximation.
DA - 2015/4//
PY - 2015/4//
DO - 10.1016/J.JMVA.2015.01.015
VL - 136
SP - 147-162
J2 - Journal of Multivariate Analysis
LA - en
OP -
SN - 0047-259X
UR - http://dx.doi.org/10.1016/J.JMVA.2015.01.015
DB - Crossref
KW - Graphical lasso
KW - Graphical models
KW - Laplace approximation
KW - Posterior convergence
KW - Precision matrix
ER -
TY - JOUR
TI - Accuracy of SNPs to predict risk of HLA alleles associated with drug-induced hypersensitivity events across racial groups
AU - He, Yijing
AU - Hoskins, Janelle M.
AU - Clark, Scott
AU - Campbell, Nathan H.
AU - Wagner, Kim
AU - Motsinger-Reif, Alison A.
AU - McLeod, Howard L.
T2 - PHARMACOGENOMICS
AB - To evaluate the potential usefulness of selected SNPs to predict specific HLA alleles that are associated with drug-induced hypersensitivity reactions (HSR) in different ethnic groups.Five specific HLA alleles known to predict HSR were tagged by seven SNPs (rs1061235-HLA-A*31:01; rs2395029-HLA-B*57:01; rs3909184-HLA-B*15:02; rs9469003-HLA-B*58:01; rs3117583-HLA-B*58:01; rs9270986-HLA-DQA1*01:02 and rs3129900-HLA-DQA1*01:02). DNA from 24 African-Americans, 56 Asian, 44 Caucasians and 36 Hispanics of known high resolution HLA-A, B and DQA1 status were genotyped for tagSNPs using TaqMan. Sensitivity and specificity were considered the primary end points and were 100% across the four populations for rs2395029-HLA-B*57:01. SNP prediction of HLA-A*31:01 had 100% sensitivity and 84% specificity.This study demonstrates the utility of SNP tagging as a 'real time' approach to predict or exclude the presence of specific HLA alleles of known importance to HSR across diverse ethnic groups. Original submitted 24 April 2014; Revision submitted 2 April 2015.
DA - 2015///
PY - 2015///
DO - 10.2217/pgs.15.41
VL - 16
IS - 8
SP - 817-824
SN - 1744-8042
KW - drug-induced hypersensitivity
KW - HLA
KW - human leukocyte antigen
KW - pharmacogenetics
KW - pharmacogenomics
KW - risk mitigation
ER -
TY - JOUR
TI - A penalized likelihood approach for investigating gene-drug interactions in pharmacogenetic studies
AU - Neely, Megan L.
AU - Bondell, Howard D.
AU - Tzeng, Jung-Ying
T2 - BIOMETRICS
AB - Pharmacogenetics investigates the relationship between heritable genetic variation and the variation in how individuals respond to drug therapies. Often, gene-drug interactions play a primary role in this response, and identifying these effects can aid in the development of individualized treatment regimes. Haplotypes can hold key information in understanding the association between genetic variation and drug response. However, the standard approach for haplotype-based association analysis does not directly address the research questions dictated by individualized medicine. A complementary post-hoc analysis is required, and this post-hoc analysis is usually under powered after adjusting for multiple comparisons and may lead to seemingly contradictory conclusions. In this work, we propose a penalized likelihood approach that is able to overcome the drawbacks of the standard approach and yield the desired personalized output. We demonstrate the utility of our method by applying it to the Scottish Randomized Trial in Ovarian Cancer. We also conducted simulation studies and showed that the proposed penalized method has comparable or more power than the standard approach and maintains low Type I error rates for both binary and quantitative drug responses. The largest performance gains are seen when the haplotype frequency is low, the difference in effect sizes are small, or the true relationship among the drugs is more complex.
DA - 2015/6//
PY - 2015/6//
DO - 10.1111/biom.12259
VL - 71
IS - 2
SP - 529-537
SN - 1541-0420
KW - Association analysis
KW - Haplotype
KW - Individualized medicine
KW - Multiple comparisons
KW - Penalized regression
KW - Pharmacogenetics
ER -
TY - JOUR
TI - A marginal cure rate proportional hazards model for spatial survival data
AU - Schnell, Patrick
AU - Bandyopadhyay, Dipankar
AU - Reich, Brian J.
AU - Nunn, Martha
T2 - JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS
AB - Dental studies often produce spatially referenced multivariate time-to-event data, such as the time until tooth loss due to periodontal disease. These data are used to identify risk factors that are associated with tooth loss, and to predict outcomes for an individual patient.The rate of spatial referencing can vary with various tooth locations. In addition, these event time data are heavily censored, mostly because a certain proportion of teeth in the population are not expected to experience failure and can be considered 'cured'. We assume a proportional hazards model with a surviving fraction to model these clustered correlated data and account for dependence between nearby teeth by using spatial frailties which are modelled as linear combinations of positive stable random effects. This model permits predictions (conditioned on spatial frailties) that account for the survival status of nearby teeth and simultaneously preserves the proportional hazards relationship marginally over the random effects for the susceptible teeth, allowing for interpretable estimates of the effects of risk factors on tooth loss. We explore the potential of this model via simulation studies and application to a real data set obtained from a private periodontal practice, and we illustrate its advantages over other competing models to identify important risk factors for tooth loss and to predict the remaining lifespan of a patient's teeth.
DA - 2015/8//
PY - 2015/8//
DO - 10.1111/rssc.12098
VL - 64
IS - 4
SP - 673-691
SN - 1467-9876
KW - Bayesian hierarchical modelling
KW - Cure rate
KW - Dental data
KW - Extreme value analysis
KW - Frailty
KW - Positive stable
KW - Tooth loss
ER -
TY - JOUR
TI - Variability of Intra-event Statistics for Multiple Fecal Indicator Bacteria in Urban Stormwater
AU - Hathaway, J. M.
AU - Hunt, W. F.
AU - McCarthy, D. T.
T2 - WATER RESOURCES MANAGEMENT
DA - 2015/8//
PY - 2015/8//
DO - 10.1007/s11269-015-1020-0
VL - 29
IS - 10
SP - 3635-3649
SN - 1573-1650
KW - Intra-event
KW - E. coli
KW - Enterococci
KW - Fecal coliform
KW - Urban stormwater
KW - Variability
ER -
TY - JOUR
TI - Toxicity testing in the 21st century beyond environmental chemicals
AU - Rovida, C.
AU - Asakura, S.
AU - Daneshian, M.
AU - Hofman-Huether, H.
AU - Leist, M.
AU - Meunier, L.
AU - Reif, D.
AU - Rossi, A.
AU - Schmutz, M.
AU - Valentin, J. P.
AU - Zurlo, J.
AU - Hartung, T.
T2 - Altex-alternatives to Animal Experimentation
DA - 2015///
PY - 2015///
VL - 32
IS - 3
SP - 171-181
ER -
TY - JOUR
TI - The new global urban realm: complex, connected, diffuse, and diverse social-ecological systems
AU - McHale, M. R.
AU - Pickett, S. T. A.
AU - Barbosa, O.
AU - Bunn, D. N.
AU - Cadenasso, M. L.
AU - Childers, D. L.
AU - Gartin, M.
AU - Hess, G. R.
AU - Iwaniec, D. M.
AU - McPhearson, T.
AU - Peterson, M. N.
AU - Poole, A. K.
AU - Rivers, L.
AU - Shutters, S. T.
AU - Zhou, W. Q.
T2 - Sustainability
DA - 2015///
PY - 2015///
VL - 7
IS - 5
SP - 5211-5240
ER -
TY - JOUR
TI - Statistical validation of structured population models for Daphnia magna
AU - Adoteye, Kaska
AU - Banks, H. T.
AU - Cross, Karissa
AU - Eytcheson, Stephanie
AU - Flores, Kevin B.
AU - LeBlanc, Gerald A.
AU - Nguyen, Timothy
AU - Ross, Chelsea
AU - Smith, Emmaline
AU - Stemkovski, Michael
AU - Stokely, Sarah
T2 - MATHEMATICAL BIOSCIENCES
AB - In this study we use statistical validation techniques to verify density-dependent mechanisms hypothesized for populations of Daphnia magna. We develop structured population models that exemplify specific mechanisms and use multi-scale experimental data in order to test their importance. We show that fecundity and survival rates are affected by both time-varying density-independent factors, such as age, and density-dependent factors, such as competition. We perform uncertainty analysis and show that our parameters are estimated with a high degree of confidence. Furthermore, we perform a sensitivity analysis to understand how changes in fecundity and survival rates affect population size and age-structure.
DA - 2015/8//
PY - 2015/8//
DO - 10.1016/j.mbs.2015.06.003
VL - 266
SP - 73-84
SN - 1879-3134
KW - Sensitivity analysis
KW - Structured population model
KW - Uncertainty quantification
KW - Density-dependence
KW - Multi-scale data
KW - Daphnia magna
ER -
TY - JOUR
TI - Path following in the exact penalty method of convex programming
AU - Zhou, Hua
AU - Lange, Kenneth
T2 - COMPUTATIONAL OPTIMIZATION AND APPLICATIONS
AB - Classical penalty methods solve a sequence of unconstrained problems that put greater and greater stress on meeting the constraints. In the limit as the penalty constant tends to ∞, one recovers the constrained solution. In the exact penalty method, squared penalties are replaced by absolute value penalties, and the solution is recovered for a finite value of the penalty constant. In practice, the kinks in the penalty and the unknown magnitude of the penalty constant prevent wide application of the exact penalty method in nonlinear programming. In this article, we examine a strategy of path following consistent with the exact penalty method. Instead of performing optimization at a single penalty constant, we trace the solution as a continuous function of the penalty constant. Thus, path following starts at the unconstrained solution and follows the solution path as the penalty constant increases. In the process, the solution path hits, slides along, and exits from the various constraints. For quadratic programming, the solution path is piecewise linear and takes large jumps from constraint to constraint. For a general convex program, the solution path is piecewise smooth, and path following operates by numerically solving an ordinary differential equation segment by segment. Our diverse applications to a) projection onto a convex set, b) nonnegative least squares, c) quadratically constrained quadratic programming, d) geometric programming, and e) semidefinite programming illustrate the mechanics and potential of path following. The final detour to image denoising demonstrates the relevance of path following to regularized estimation in inverse problems. In regularized estimation, one follows the solution path as the penalty constant decreases from a large value.
DA - 2015/7//
PY - 2015/7//
DO - 10.1007/s10589-015-9732-x
VL - 61
IS - 3
SP - 609-634
SN - 1573-2894
KW - Constrained convex optimization
KW - Exact penalty
KW - Geometric programming
KW - Ordinary differential equation
KW - Quadratically constrained quadratic programming
KW - Regularization
KW - Semidefinite programming
ER -
TY - JOUR
TI - New Statistical Learning Methods for Estimating Optimal Dynamic Treatment Regimes
AU - Zhao, Ying-Qi
AU - Zeng, Donglin
AU - Laber, Eric B.
AU - Kosorok, Michael R.
T2 - JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
AB - Dynamic treatment regimes (DTRs) are sequential decision rules for individual patients that can adapt over time to an evolving illness. The goal is to accommodate heterogeneity among patients and find the DTR which will produce the best long term outcome if implemented. We introduce two new statistical learning methods for estimating the optimal DTR, termed backward outcome weighted learning (BOWL), and simultaneous outcome weighted learning (SOWL). These approaches convert individualized treatment selection into an either sequential or simultaneous classification problem, and can thus be applied by modifying existing machine learning techniques. The proposed methods are based on directly maximizing over all DTRs a nonparametric estimator of the expected long-term outcome; this is fundamentally different than regression-based methods, for example Q-learning, which indirectly attempt such maximization and rely heavily on the correctness of postulated regression models. We prove that the resulting rules are consistent, and provide finite sample bounds for the errors using the estimated rules. Simulation results suggest the proposed methods produce superior DTRs compared with Q-learning especially in small samples. We illustrate the methods using data from a clinical trial for smoking cessation.
DA - 2015/6//
PY - 2015/6//
DO - 10.1080/01621459.2014.937488
VL - 110
IS - 510
SP - 583-598
SN - 1537-274X
KW - Classification
KW - Personalized medicine
KW - Q-learning
KW - Reinforcement learning
KW - Risk bound
KW - Support vector machine
ER -
TY - JOUR
TI - Modeling Climate Change Effects on the Height Growth of Loblolly Pine
AU - Farjat, Alfredo E.
AU - Isik, Fikret
AU - Reich, Brian J.
AU - Whetten, Ross W.
AU - McKeand, Steven E.
T2 - FOREST SCIENCE
AB - We present a statistical model to predict the effects of climate change on the height growth of loblolly pine (Pinus taeda L.) families in the southeastern United States. Provenance-progeny trials were used for assessing the response of loblolly pine seed sources to environmental change. Ordinary least squares, ridge regression, and LASSO regression were used to develop height growth prediction models. The approach integrates both genetic and environmental effects and is meant to overcome the critical limitations of population response function and transfer function methods by making full use of data from provenance trials. Prediction models were tested using a hypothetical future climate scenario with 5% decrease in precipitation and 0.5° C increase in maximum and minimum temperatures, relative to historical average values. Under this scenario, local families from the coastal plains of Georgia, Florida, and South Carolina showed the highest performance relative to the current climate in their native environments. As these seed sources were moved to colder northern and inland regions from their origin, we observed declines in their height growth. Similarly, the climatic change scenario suggested that performance of northern seed sources declined significantly when they were moved to more southern warmer regions. The statistical model can be used as a quantitative tool to model the effect of climatic variables on the performance of loblolly pine seed sources and may help to develop sound breeding deployment strategies.
DA - 2015/8//
PY - 2015/8//
DO - 10.5849/forsci.14-075
VL - 61
IS - 4
SP - 703-715
SN - 1938-3738
KW - Pinus taeda
KW - provenance test
KW - statistical model
KW - universal response function
KW - climate change
ER -
TY - JOUR
TI - Medullary Position at the Craniocervical Junction in Mature Cavalier King Charles Spaniels: Relationship with Neurologic Signs and Syringomyelia
AU - Cerda-Gonzalez, S.
AU - Olby, N. J.
AU - Griffith, E. H.
T2 - JOURNAL OF VETERINARY INTERNAL MEDICINE
AB - Medullary elevation (ie, medullary kinking) at the craniocervical junction (CCJ) is reported in dogs with Chiari-like malformations (CM), but its diagnostic criteria and clinical relevance are unclear.To describe the position of the medulla at the CCJ in mature cavalier King Charles spaniels (CKCS), and evaluate its relationship with clinical status and the presence of syringomyelia.Thirty-six CKCS, 5-12 years of age, including 16 asymptomatic dogs.Dogs were assigned a neurologic grade; magnetic resonance imaging (MRI) of the CCJ then was performed. The presence of a CM and syringomyelia was recorded and syringomyelia severity was quantified. Medullary position was quantified using the medullary kinking index, the elevation angle and obex position relative to the foramen magnum. The relationship between medullary position measures and presence and severity of neurologic signs and syringomyelia was investigated.Chiari-like malformation was found in 33 dogs; 26 of them had syringomyelia. Mean medullary kinking index was 46.4% (SD, 10.3), elevation angle was 132° (SD, 12) and obex position was 3.5 mm (SD, 0.8). A higher medullary kinking index was associated with the presence of neurologic signs (P = .0368). Obex position was associated with the presence (P = .0018) and severity of syringomyelia (P = .0164).There is a significant association between medullary elevation and clinical signs, whereas more caudal brainstem positions appear related to the presence of syringomyelia.
DA - 2015///
PY - 2015///
DO - 10.1111/jvim.12605
VL - 29
IS - 3
SP - 882-886
SN - 1939-1676
KW - Cervicomedullary
KW - Chiari-like
KW - Medullary elevation
KW - Medullary kinking
ER -
TY - JOUR
TI - Integrating acoustic telemetry into mark-recapture models to improve the precision of apparent survival and abundance estimates
AU - Dudgeon, Christine L.
AU - Pollock, Kenneth H.
AU - Braccini, J. Matias
AU - Semmens, Jayson M.
AU - Barnett, Adam
T2 - OECOLOGIA
DA - 2015/7//
PY - 2015/7//
DO - 10.1007/s00442-015-3280-z
VL - 178
IS - 3
SP - 761-772
SN - 1432-1939
KW - CJS
KW - JS
KW - POPAN
KW - Broadnose sevengill sharks
KW - Capture-recapture
KW - Population estimation
ER -
TY - JOUR
TI - Information content in data sets for a nucleated-polymerization model
AU - Banks, H. T.
AU - Doumic, Marie
AU - Kruse, Carola
AU - Prigent, Stephanie
AU - Rezaei, Human
T2 - JOURNAL OF BIOLOGICAL DYNAMICS
AB - We illustrate the use of statistical tools (asymptotic theories of standard error quantification using appropriate statistical models, bootstrapping, and model comparison techniques) in addition to sensitivity analysis that may be employed to determine the information content in data sets. We do this in the context of recent models [S. Prigent, A. Ballesta, F. Charles, N. Lenuzza, P. Gabriel, L.M. Tine, H. Rezaei, and M. Doumic, An efficient kinetic model for assemblies of amyloid fibrils and its application to polyglutamine aggregation, PLoS ONE 7 (2012), e43273. doi:10.1371/journal.pone.0043273.] for nucleated polymerization in proteins, about which very little is known regarding the underlying mechanisms; thus, the methodology we develop here may be of great help to experimentalists. We conclude that the investigated data sets will support with reasonable levels of uncertainty only the estimation of the parameters related to the early steps of the aggregation process.
DA - 2015/1/1/
PY - 2015/1/1/
DO - 10.1080/17513758.2015.1050465
VL - 9
IS - 1
SP - 172-197
SN - 1751-3766
KW - inverse problems
KW - polyglutamine and aggregation modelling
KW - information content
KW - sensitivity
KW - uncertainty quantification
KW - 65M32
KW - 62P10
KW - 64B10
KW - 49Q12
ER -
TY - JOUR
TI - Identification of novel gene targets and putative regulators of arsenic-associated DNA methylation in human urothelial cells and bladder cancer
AU - Rager, J. E.
AU - Tilley, S. K.
AU - Tulenko, S. E.
AU - Smeester, L.
AU - Ray, P. D.
AU - Yosim, A.
AU - Currier, J. M.
AU - Ishida, M. C.
AU - Gonzalez-Horta, M. D.
AU - Sanchez-Ramirez, B.
AU - Ballinas-Casarrubias, L.
AU - Gutierrez-Torres, D. S.
AU - Drobna, Z.
AU - Del Razo, L. M.
T2 - Chemical Research in Toxicology
DA - 2015///
PY - 2015///
VL - 28
IS - 6
SP - 1144-1155
ER -
TY - JOUR
TI - Fungi Identify the Geographic Origin of Dust Samples
AU - Grantham, Neal S.
AU - Reich, Brian J.
AU - Pacifici, Krishna
AU - Laber, Eric B.
AU - Menninger, Holly L.
AU - Henley, Jessica B.
AU - Barberan, Albert
AU - Leff, Jonathan W.
AU - Fierer, Noah
AU - Dunn, Robert R.
T2 - PLOS ONE
AB - There is a long history of archaeologists and forensic scientists using pollen found in a dust sample to identify its geographic origin or history. Such palynological approaches have important limitations as they require time-consuming identification of pollen grains, a priori knowledge of plant species distributions, and a sufficient diversity of pollen types to permit spatial or temporal identification. We demonstrate an alternative approach based on DNA sequencing analyses of the fungal diversity found in dust samples. Using nearly 1,000 dust samples collected from across the continental U.S., our analyses identify up to 40,000 fungal taxa from these samples, many of which exhibit a high degree of geographic endemism. We develop a statistical learning algorithm via discriminant analysis that exploits this geographic endemicity in the fungal diversity to correctly identify samples to within a few hundred kilometers of their geographic origin with high probability. In addition, our statistical approach provides a measure of certainty for each prediction, in contrast with current palynology methods that are almost always based on expert opinion and devoid of statistical inference. Fungal taxa found in dust samples can therefore be used to identify the origin of that dust and, more importantly, we can quantify our degree of certainty that a sample originated in a particular place. This work opens up a new approach to forensic biology that could be used by scientists to identify the origin of dust or soil samples found on objects, clothing, or archaeological artifacts.
DA - 2015/4/13/
PY - 2015/4/13/
DO - 10.1371/journal.pone.0122605
VL - 10
IS - 4
SP -
SN - 1932-6203
ER -
TY - JOUR
TI - Functional additive mixed models
AU - Scheipl, F.
AU - Staicu, Ana-Maria
AU - Greven, S.
T2 - Journal of Computational and Graphical Statistics
AB - We propose an extensive framework for additive regression models for correlated functional responses, allowing for multiple partially nested or crossed functional random effects with flexible correlation structures for, for example, spatial, temporal, or longitudinal functional data. Additionally, our framework includes linear and nonlinear effects of functional and scalar covariates that may vary smoothly over the index of the functional response. It accommodates densely or sparsely observed functional responses and predictors which may be observed with additional error and includes both spline-based and functional principal component-based terms. Estimation and inference in this framework is based on standard additive mixed models, allowing us to take advantage of established methods and robust, flexible algorithms. We provide easy-to-use open source software in the pffr() function for the R package refund. Simulations show that the proposed method recovers relevant effects reliably, handles small sample sizes well, and also scales to larger datasets. Applications with spatially and longitudinally observed functional data demonstrate the flexibility in modeling and interpretability of results of our approach.
DA - 2015///
PY - 2015///
DO - 10.1080/10618600.2014.901914
VL - 24
IS - 2
SP - 477–501
ER -
TY - JOUR
TI - Dorsal Compressive Atlantoaxial Bands and the Craniocervical Junction Syndrome: Association with Clinical Signs and Syringomyelia in Mature Cavalier King Charles Spaniels
AU - Cerda-Gonzalez, S.
AU - Olby, N. J.
AU - Griffith, E. H.
T2 - JOURNAL OF VETERINARY INTERNAL MEDICINE
AB - Dorsal compressive lesions at the atlantoaxial junction (ie, AA bands) occur in dogs with Chiari-like malformations (CMs), but their clinical relevance is unclear.Investigate the influence of AA bands on clinical status and syringomyelia (SM) in mature cavalier King Charles spaniels (CKCS).Thirty-six CKCS, 5-12 years of age, including 20 dogs with neuropathic pain.Dogs were examined and assigned a neurologic grade. Magnetic resonance imaging (MRI) of the craniocervical junction was performed with the craniocervical junction extended and flexed (ie, normal standing position). Imaging studies were assessed for the presence of an AA band, CM, SM or some combination of these findings. Band and SM severity were quantified using an objective compression index and ordinal grading scale, respectively.Of 36 CKCS imaged, 34 had CM. Atlantoaxial bands were associated with the presence (P = .0031) but not the severity (P = .008) of clinical signs, whereas their presence was associated with both the presence and severity of SM (P = .0147, P = .0311, respectively ). Higher compression indices were associated with more severe SM (P = .0137).Prevalence of AA bands in older CKCS is high. Positioning of dogs in extension during MRI enhances the sensitivity of the study for detecting this important abnormality. There were significant associations among AA bands, clinical signs, and SM in dogs with CM; additional work is needed to understand whether or not this relationship is causal.
DA - 2015///
PY - 2015///
DO - 10.1111/jvim.12604
VL - 29
IS - 3
SP - 887-892
SN - 1939-1676
KW - Chiari-like
KW - Compression index
KW - Fibrous band
KW - Magnetic resonance imaging
ER -
TY - JOUR
TI - Do growing degree days predict phenology across butterfly species?
AU - Cayton, Heather L.
AU - Haddad, Nick M.
AU - Gross, Kevin
AU - Diamond, Sarah E.
AU - Ries, Leslie
T2 - ECOLOGY
AB - Global climate change is causing shifts in phenology across multiple species. We use a geographically and temporally extensive data set of butterfly abundance across the state of Ohio to ask whether phenological change can be predicted from climatological data. Our focus is on growing degree days (GDD), a commonly used measure of thermal accumulation, as the mechanistic link between climate change and species phenology. We used simple calculations of median absolute error associated with GDD and an alternative predictor of phenology, ordinal date, for both first emergence and peak abundance of 13 butterfly species. We show that GDD acts as a better predictor than date for first emergence in nearly all species, and for peak abundance in more than half of all species, especially univoltine species. Species with less ecological flexibility, in particular those with greater dietary specialization, had greater predictability with GDD. The new method we develop for predicting phenology using GDD offers a simple yet effective way to predict species' responses to climate change.
DA - 2015/6//
PY - 2015/6//
DO - 10.1890/15-0131.1
VL - 96
IS - 6
SP - 1473-1479
SN - 1939-9170
KW - climate change
KW - first emergence
KW - growing degree days
KW - Lepidoptera
KW - Ohio, USA
KW - ordinal date
KW - peak abundance
KW - phenology
KW - temperature
ER -
TY - JOUR
TI - Discussion of "Frequentist coverage of adaptive nonparametric Bayesian credible sets"
AU - Ghosal, S.
T2 - Annals of Statistics
DA - 2015///
PY - 2015///
VL - 43
IS - 4
SP - 1455-1462
ER -
TY - JOUR
TI - Assessing Variability of Complex Descriptive Statistics in Monte Carlo Studies Using Resampling Methods
AU - Boos, Dennis D.
AU - Osborne, Jason A.
T2 - INTERNATIONAL STATISTICAL REVIEW
AB - Good statistical practice dictates that summaries in Monte Carlo studies should always be accompanied by standard errors. Those standard errors are easy to provide for summaries that are sample means over the replications of the Monte Carlo output: for example, bias estimates, power estimates for tests, and mean squared error estimates. But often more complex summaries are of interest: medians (often displayed in boxplots), sample variances, ratios of sample variances, and non-normality measures like skewness and kurtosis. In principle standard errors for most of these latter summaries may be derived from the Delta Method, but that extra step is often a barrier for standard errors to be provided. Here we highlight the simplicity of using the jackknife and bootstrap to compute these standard errors, even when the summaries are somewhat complicated.
DA - 2015/8//
PY - 2015/8//
DO - 10.1111/insr.12087
VL - 83
IS - 2
SP - 228-238
SN - 1751-5823
KW - Bootstrap
KW - jackknife
KW - coefficient of variation
KW - delta method
KW - influence curve
KW - standard errors
KW - variability of ratios
ER -
TY - JOUR
TI - A Two-Sample Test for Equality of Means in High Dimension
AU - Gregory, Karl Bruce
AU - Carroll, Raymond J.
AU - Baladandayuthapani, Veerabhadran
AU - Lahiri, Soumendra N.
T2 - JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
AB - We develop a test statistic for testing the equality of two population mean vectors in the “large-p-small-n” setting. Such a test must surmount the rank-deficiency of the sample covariance matrix, which breaks down the classic Hotelling T2 test. The proposed procedure, called the generalized component test, avoids full estimation of the covariance matrix by assuming that the p components admit a logical ordering such that the dependence between components is related to their displacement. The test is shown to be competitive with other recently developed methods under ARMA and long-range dependence structures and to achieve superior power for heavy-tailed data. The test does not assume equality of covariance matrices between the two populations, is robust to heteroscedasticity in the component variances, and requires very little computation time, which allows its use in settings with very large p. An analysis of mitochondrial calcium concentration in mouse cardiac muscles over time and of copy number variations in a glioblastoma multiforme dataset from The Cancer Genome Atlas are carried out to illustrate the test. Supplementary materials for this article are available online.
DA - 2015/6//
PY - 2015/6//
DO - 10.1080/01621459.2014.934826
VL - 110
IS - 510
SP - 837-849
SN - 1537-274X
KW - Copy number variation
KW - Heteroscedasticity
KW - Large p
ER -
TY - JOUR
TI - A SMOOTH BLOCK BOOTSTRAP FOR STATISTICAL FUNCTIONALS AND TIME SERIES
AU - Gregory, Karl B.
AU - Lahiri, Soumendra N.
AU - Nordman, Daniel J.
T2 - JOURNAL OF TIME SERIES ANALYSIS
AB - Unlike with independent data, smoothed bootstraps have received little consideration for time series, although data smoothing within resampling can improve bootstrap approximations, especially when target distributions depend on smooth population quantities (e.g., marginal densities). For approximating a broad class statistics formulated through statistical functionals (e.g., LL‐estimators, and sample quantiles), we propose a smooth bootstrap by modifying a state‐of‐the‐art (extended) tapered block bootstrap (TBB). Our treatment shows that the smooth TBB applies to time series inference cases not formally established with other TBB versions. Simulations also indicate that smoothing enhances the block bootstrap.
DA - 2015/5//
PY - 2015/5//
DO - 10.1111/jtsa.12117
VL - 36
IS - 3
SP - 442-461
SN - 1467-9892
KW - L-estimators
KW - M-estimators
KW - sample quantiles
KW - tapered block bootstrap
KW - JEL Primary 62G09
KW - Secondary 62G20
KW - 62J05
KW - 62M10
ER -
TY - JOUR
TI - A Content Analysis of Mission Statements of Our Top 50 Schools of Social Work
AU - Holosko, Michael J.
AU - Winkel, Munir
AU - Crandall, Catherine
AU - Briggs, Harold
T2 - JOURNAL OF SOCIAL WORK EDUCATION
AB - Organizational mission statements of institutions in higher education have been called into question with respect to their relevance and purpose. This study investigated mission statements of the top 50 U.S. News & World Report (2012) ranked schools of social work for their clarity and brevity, content, and relationship to the Council on Social Work Education’s core competencies. A content analysis of these statements raises concerns about their quality and overall function and poses considerable doubts about their overall relevance and usefulness. Implications are directed to all stakeholders concerned about the content and accuracy of school of social work mission statements. The study addresses a distinct void in the literature in this important subject matter.
DA - 2015/4/3/
PY - 2015/4/3/
DO - 10.1080/10437797.2015.1012922
VL - 51
IS - 2
SP - 222-236
SN - 2163-5811
ER -
TY - JOUR
TI - Quality of Life and Obstructive Sleep Apnea Symptoms After Pediatric Adenotonsillectomy
AU - Garetz, Susan L.
AU - Mitchell, Ron B.
AU - Parker, Portia D.
AU - Moore, Renee H.
AU - Rosen, Carol L.
AU - Giordani, Bruno
AU - Muzumdar, Hiren
AU - Paruthi, Shalini
AU - Elden, Lisa
AU - Willging, Paul
AU - Beebe, Dean W.
AU - Marcus, Carole L.
AU - Chervin, Ronald D.
AU - Redline, Susan
T2 - PEDIATRICS
AB - Data from a randomized, controlled study of adenotonsillectomy for obstructive sleep apnea syndrome (OSAS) were used to test the hypothesis that children undergoing surgery had greater quality of life (QoL) and symptom improvement than control subjects. The objectives were to compare changes in validated QoL and symptom measurements among children randomized to undergo adenotonsillectomy or watchful waiting; to determine whether race, weight, or baseline OSAS severity influenced changes in QoL and symptoms; and to evaluate associations between changes in QoL or symptoms and OSAS severity.Children aged 5 to 9.9 years with OSAS (N = 453) were randomly assigned to undergo adenotonsillectomy or watchful waiting with supportive care. Polysomnography, the Pediatric Quality of Life inventory, the Sleep-Related Breathing Scale of the Pediatric Sleep Questionnaire, the 18-item Obstructive Sleep Apnea QoL instrument, and the modified Epworth Sleepiness Scale were completed at baseline and 7 months. Changes in the QoL and symptom surveys were compared between arms. Effect modification according to race and obesity and associations between changes in polysomnographic measures and QoL or symptoms were examined.Greater improvements in most QoL and symptom severity measurements were observed in children randomized to undergo adenotonsillectomy, including the parent-completed Pediatric Quality of Life inventory (effect size [ES]: 0.37), the 18-item Obstructive Sleep Apnea QoL instrument (ES: -0.93), the modified Epworth Sleepiness Scale score (ES: -0.42), and the Sleep-Related Breathing Scale of the Pediatric Sleep Questionnaire (ES: -1.35). Effect modification was not observed by obesity or baseline severity but was noted for race in some symptom measures. Improvements in OSAS severity explained only a small portion of the observed changes.Adenotonsillectomy compared with watchful waiting resulted in significantly more improvements in parent-rated generic and OSAS-specific QoL measures and OSAS symptoms.
DA - 2015/2//
PY - 2015/2//
DO - 10.1542/peds.2014-0620
VL - 135
IS - 2
SP - E477-E486
SN - 1098-4275
ER -
TY - JOUR
TI - Population-Based in Vitro Hazard and Concentration-Response Assessment of Chemicals: The 1000 Genomes High-Throughput Screening Study
AU - Abdo, Nour
AU - Xia, Menghang
AU - Brown, Chad C.
AU - Kosyk, Oksana
AU - Huang, Ruili
AU - Sakamuru, Srilatha
AU - Zhou, Yi-Hui
AU - Jack, John R.
AU - Gallins, Paul
AU - Xia, Kai
AU - Li, Yun
AU - Chiu, Weihsueh A.
AU - Motsinger-Reif, Alison A.
AU - Austin, Christopher P.
AU - Tice, Raymond R.
AU - Rusyn, Ivan
AU - Wright, Fred A.
T2 - ENVIRONMENTAL HEALTH PERSPECTIVES
AB - Understanding of human variation in toxicity to environmental chemicals remains limited, so human health risk assessments still largely rely on a generic 10-fold factor (10½ each for toxicokinetics and toxicodynamics) to account for sensitive individuals or subpopulations.We tested a hypothesis that population-wide in vitro cytotoxicity screening can rapidly inform both the magnitude of and molecular causes for interindividual toxicodynamic variability.We used 1,086 lymphoblastoid cell lines from the 1000 Genomes Project, representing nine populations from five continents, to assess variation in cytotoxic response to 179 chemicals. Analysis included assessments of population variation and heritability, and genome-wide association mapping, with attention to phenotypic relevance to human exposures.For about half the tested compounds, cytotoxic response in the 1% most "sensitive" individual occurred at concentrations within a factor of 10½ (i.e., approximately 3) of that in the median individual; however, for some compounds, this factor was > 10. Genetic mapping suggested important roles for variation in membrane and transmembrane genes, with a number of chemicals showing association with SNP rs13120371 in the solute carrier SLC7A11, previously implicated in chemoresistance.This experimental approach fills critical gaps unaddressed by recent large-scale toxicity testing programs, providing quantitative, experimentally based estimates of human toxicodynamic variability, and also testable hypotheses about mechanisms contributing to interindividual variation.
DA - 2015/5//
PY - 2015/5//
DO - 10.1289/ehp.1408775
VL - 123
IS - 5
SP - 458-466
SN - 1552-9924
ER -
TY - JOUR
TI - Optimal sampling frequency and timing of threatened tropical bird populations: A modeling approach
AU - Banks, J. E.
AU - Banks, H. T.
AU - Rinnovatore, K.
AU - Jackson, C. M.
T2 - ECOLOGICAL MODELLING
AB - Abstract Conservation of threatened or endangered species relies critically on accurate population counts over time. In practice, many population censuses are conducted by non-governmental organizations or volunteer citizen scientists who are constrained by fiscal and temporal resources. Less than optimal sampling regimens (characterized by infrequent and/or irregular schedules) for conducting population censuses can result in woefully misleading population estimates – and thus have dire consequences for management and conservation. We illustrate this using an East African case study in which 14 years of bird data was collected in the Arabuko-Sokoke Forest in coastal Kenya. We first estimate life history parameters in a discrete matrix model. Desiring a data collection protocol which would lessen observation error and lend to a deeper understanding of population projections and dynamics of a threatened species, we carry out mathematical and statistical modeling efforts with an adaptation of a Leslie model for simulated population estimates stemming from different population sampling schemes. We illustrate how resource managers might take a strategic approach, using simple quantitative models, to develop an optimal sampling scheme that considers important species traits, such as breeding season, and balances the tradeoff between resources and accuracy.
DA - 2015/5/10/
PY - 2015/5/10/
DO - 10.1016/j.ecolmodel.2015.02.005
VL - 303
SP - 70-77
SN - 1872-7026
KW - Arabuko-Sokoke Forest
KW - Inverse problem
KW - Kenya
KW - Least squares optimization
KW - Leslie matrix
KW - Sheppardia gunningi
ER -
TY - JOUR
TI - Operative factors associated with short-term outcome in horses with large colon volvulus: 47 cases from 2006 to 2013
AU - Gonzalez, L. M.
AU - Fogle, C. A.
AU - Baker, W. T.
AU - Hughes, F. E.
AU - Law, J. M.
AU - Motsinger-Reif, A. A.
AU - Blikslager, A. T.
T2 - EQUINE VETERINARY JOURNAL
AB - There is an important need for objective parameters that accurately predict the outcome of horses with large colon volvulus.To evaluate the predictive value of a series of histomorphometric parameters on short-term outcome, as well as the impact of colonic resection on horses with large colon volvulus.Retrospective cohort study.Adult horses admitted to the Equine and Farm Animal Veterinary Center at North Carolina State University, Peterson and Smith and Chino Valley Equine Hospitals between 2006 and 2013 that underwent an exploratory coeliotomy, diagnosed with large colon volvulus of ≥360 degrees, where a pelvic flexure biopsy was obtained, and that recovered from general anaesthesia, were selected for inclusion in the study. Logistic regression was used to determine associations between signalment, histomorphometric measurements of interstitium-to-crypt ratio, degree of haemorrhage, percentage loss of luminal and glandular epithelium, as well as colonic resection with short-term outcome (discharge from the hospital).Pelvic flexure biopsies from 47 horses with large colon volvulus were evaluated. Factors that were significantly associated with short-term outcome on univariate logistic regression were Thoroughbred breed (P = 0.04), interstitium-to-crypt ratio >1 (P = 0.02) and haemorrhage score ≥3 (P = 0.005). Resection (P = 0.92) was not found to be associated significantly with short-term outcome. No combined factors increased the likelihood of death in forward stepwise logistic regression modelling. A digitally quantified measurement of haemorrhage area strengthened the association of haemorrhage with nonsurvival in cases of large colon volvulus.Histomorphometric measurements of interstitium-to-crypt ratio and degree of haemorrhage predict short-term outcome in cases of large colon volvulus. Resection was not associated with short-term outcome in horses selected for this study. Accurate quantification of mucosal haemorrhage at the time of surgery may improve veterinary surgeons' prognostic capabilities in horses with large colon volvulus.
DA - 2015/5//
PY - 2015/5//
DO - 10.1111/evj.12273
VL - 47
IS - 3
SP - 279-284
SN - 2042-3306
KW - horse
KW - large colon volvulus
KW - strangulation
KW - pelvic flexure
KW - surgery
ER -
TY - JOUR
TI - Likelihood approximations for big nonstationary spatial temporal lattice data
AU - Guinness, J.
AU - Fuentes, M.
T2 - Statistica Sinica
DA - 2015///
PY - 2015///
VL - 25
IS - 1
SP - 329-349
ER -
TY - JOUR
TI - Incorporating covariates in skewed functional data models
AU - Li, M.
AU - Staicu, Ana-Maria
AU - Bondell, H. D.
T2 - Biostatistics (Oxford, England)
AB - We introduce a class of covariate-adjusted skewed functional models (cSFM) designed for functional data exhibiting location-dependent marginal distributions. We propose a semi-parametric copula model for the pointwise marginal distributions, which are allowed to depend on covariates, and the functional dependence, which is assumed covariate invariant. The proposed cSFM framework provides a unifying platform for pointwise quantile estimation and trajectory prediction. We consider a computationally feasible procedure that handles densely as well as sparsely observed functional data. The methods are examined numerically using simulations and is applied to a new tractography study of multiple sclerosis. Furthermore, the methodology is implemented in the R package cSFM, which is publicly available on CRAN.
DA - 2015///
PY - 2015///
DO - 10.1093/biostatistics/kxu055
VL - 16
IS - 3
SP - 413–426
ER -
TY - JOUR
TI - Immuno-modulatory strategies for reduction of HIV reservoir cells
AU - Banks, H. T.
AU - Flores, Kevin B.
AU - Hu, Shuhua
AU - Rosenberg, Eric
AU - Buzon, Maria
AU - Yu, Xu
AU - Lichterfeld, Matthias
T2 - JOURNAL OF THEORETICAL BIOLOGY
AB - Antiretroviral therapy is able to suppress the viral load to below the detection limit, but it is not able to eradicate HIV reservoirs. Thus, there is a critical need for a novel treatment to eradicate (or reduce) the reservoir in order to eliminate the need for a lifelong adherence to antiretroviral therapy, which is expensive and potentially toxic. In this paper, we investigate the possible pharmacological strategies or combinations of strategies that may be beneficial to reduce or possibly eradicate the latent reservoir. We do this via studies with a validated mathematical model, where the parameter values are obtained with newly acquired clinical data for HIV patients. Our findings indicate that the strategy of reactivating the reservoir combined with enhancement of the killing rate of HIV-specific CD8+ T cells is able to eradicate the reservoir. In addition, our analysis shows that a targeted suppression of the immune system is also a possible strategy to eradicate the reservoir.
DA - 2015/5/7/
PY - 2015/5/7/
DO - 10.1016/j.jtbi.2015.02.006
VL - 372
SP - 146-158
SN - 1095-8541
KW - Immune response
KW - Mathematical model
KW - Inverse problem
KW - Stability analysis
ER -
TY - JOUR
TI - Hypothesis testing at the extremes: fast and robust association for high-throughput data
AU - Zhou, Yi-Hui
AU - Wright, Fred A.
T2 - BIOSTATISTICS
AB - A number of biomedical problems require performing many hypothesis tests, with an attendant need to apply stringent thresholds. Often the data take the form of a series of predictor vectors, each of which must be compared with a single response vector, perhaps with nuisance covariates. Parametric tests of association are often used, but can result in inaccurate type I error at the extreme thresholds, even for large sample sizes. Furthermore, standard two-sided testing can reduce power compared with the doubled [Formula: see text]-value, due to asymmetry in the null distribution. Exact (permutation) testing is attractive, but can be computationally intensive and cumbersome. We present an approximation to exact association tests of trend that is accurate and fast enough for standard use in high-throughput settings, and can easily provide standard two-sided or doubled [Formula: see text]-values. The approach is shown to be equivalent under permutation to likelihood ratio tests for the most commonly used generalized linear models (GLMs). For linear regression, covariates are handled by working with covariate-residualized responses and predictors. For GLMs, stratified covariates can be handled in a manner similar to exact conditional testing. Simulations and examples illustrate the wide applicability of the approach. The accompanying mcc package is available on CRAN http://cran.r-project.org/web/packages/mcc/index.html.
DA - 2015/7//
PY - 2015/7//
DO - 10.1093/biostatistics/kxv007
VL - 16
IS - 3
SP - 611-625
SN - 1468-4357
KW - Density approximation
KW - Exact testing
KW - Permutation
ER -
TY - JOUR
TI - Homogeneity Pursuit
AU - Ke, Zheng Tracy
AU - Fan, Jianqing
AU - Wu, Yichao
T2 - JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
AB - This paper explores the homogeneity of coefficients in high-dimensional regression, which extends the sparsity concept and is more general and suitable for many applications. Homogeneity arises when regression coefficients corresponding to neighboring geographical regions or a similar cluster of covariates are expected to be approximately the same. Sparsity corresponds to a special case of homogeneity with a large cluster of known atom zero. In this article, we propose a new method called clustering algorithm in regression via data-driven segmentation (CARDS) to explore homogeneity. New mathematics are provided on the gain that can be achieved by exploring homogeneity. Statistical properties of two versions of CARDS are analyzed. In particular, the asymptotic normality of our proposed CARDS estimator is established, which reveals better estimation accuracy for homogeneous parameters than that without homogeneity exploration. When our methods are combined with sparsity exploration, further efficiency can be achieved beyond the exploration of sparsity alone. This provides additional insights into the power of exploring low-dimensional structures in high-dimensional regression: homogeneity and sparsity. Our results also shed lights on the properties of the fussed Lasso. The newly developed method is further illustrated by simulation studies and applications to real data. Supplementary materials for this article are available online.
DA - 2015/3//
PY - 2015/3//
DO - 10.1080/01621459.2014.892882
VL - 110
IS - 509
SP - 175-194
SN - 1537-274X
KW - Clustering
KW - Sparsity
ER -
TY - JOUR
TI - Gene Expression in Transformed Lymphocytes Reveals Variation in Endomembrane and HLA Pathways Modifying Cystic Fibrosis Pulmonary Phenotypes
AU - O’Neal, Wanda K.
AU - Gallins, Paul
AU - Pace, Rhonda G.
AU - Dang, Hong
AU - Wolf, Whitney E.
AU - Jones, Lisa C.
AU - Guo, XueLiang
AU - Zhou, Yi-Hui
AU - Madar, Vered
AU - Huang, Jinyan
AU - Liang, Liming
AU - Moffatt, Miriam F.
AU - Cutting, Garry R.
AU - Drumm, Mitchell L.
AU - Rommens, Johanna M.
AU - Strug, Lisa J.
AU - Sun, Wei
AU - Stonebraker, Jaclyn R.
AU - Wright, Fred A.
AU - Knowles, Michael R.
T2 - The American Journal of Human Genetics
AB - Variation in cystic fibrosis (CF) phenotypes, including lung disease severity, age of onset of persistent Pseudomonas aeruginosa (P. aeruginosa) lung infection, and presence of meconium ileus (MI), has been partially explained by genome-wide association studies (GWASs). It is not expected that GWASs alone are sufficiently powered to uncover all heritable traits associated with CF phenotypic diversity. Therefore, we utilized gene expression association from lymphoblastoid cells lines from 754 p.Phe508del CF-affected homozygous individuals to identify genes and pathways. LPAR6, a G protein coupled receptor, associated with lung disease severity (false discovery rate q value = 0.0006). Additional pathway analyses, utilizing a stringent permutation-based approach, identified unique signals for all three phenotypes. Pathways associated with lung disease severity were annotated in three broad categories: (1) endomembrane function, containing p.Phe508del processing genes, providing evidence of the importance of p.Phe508del processing to explain lung phenotype variation; (2) HLA class I genes, extending previous GWAS findings in the HLA region; and (3) endoplasmic reticulum stress response genes. Expression pathways associated with lung disease were concordant for some endosome and HLA pathways, with pathways identified using GWAS associations from 1,978 CF-affected individuals. Pathways associated with age of onset of persistent P. aeruginosa infection were enriched for HLA class II genes, and those associated with MI were related to oxidative phosphorylation. Formal testing demonstrated that genes showing differential expression associated with lung disease severity were enriched for heritable genetic variation and expression quantitative traits. Gene expression provided a powerful tool to identify unrecognized heritable variation, complementing ongoing GWASs in this rare disease. Variation in cystic fibrosis (CF) phenotypes, including lung disease severity, age of onset of persistent Pseudomonas aeruginosa (P. aeruginosa) lung infection, and presence of meconium ileus (MI), has been partially explained by genome-wide association studies (GWASs). It is not expected that GWASs alone are sufficiently powered to uncover all heritable traits associated with CF phenotypic diversity. Therefore, we utilized gene expression association from lymphoblastoid cells lines from 754 p.Phe508del CF-affected homozygous individuals to identify genes and pathways. LPAR6, a G protein coupled receptor, associated with lung disease severity (false discovery rate q value = 0.0006). Additional pathway analyses, utilizing a stringent permutation-based approach, identified unique signals for all three phenotypes. Pathways associated with lung disease severity were annotated in three broad categories: (1) endomembrane function, containing p.Phe508del processing genes, providing evidence of the importance of p.Phe508del processing to explain lung phenotype variation; (2) HLA class I genes, extending previous GWAS findings in the HLA region; and (3) endoplasmic reticulum stress response genes. Expression pathways associated with lung disease were concordant for some endosome and HLA pathways, with pathways identified using GWAS associations from 1,978 CF-affected individuals. Pathways associated with age of onset of persistent P. aeruginosa infection were enriched for HLA class II genes, and those associated with MI were related to oxidative phosphorylation. Formal testing demonstrated that genes showing differential expression associated with lung disease severity were enriched for heritable genetic variation and expression quantitative traits. Gene expression provided a powerful tool to identify unrecognized heritable variation, complementing ongoing GWASs in this rare disease. The genetic architecture of phenotypic variability in cystic fibrosis (CF [MIM 219700]) is beginning to be defined,1Wright F.A. Strug L.J. Doshi V.K. Commander C.W. Blackman S.M. Sun L. Berthiaume Y. Cutler D. Cojocaru A. Collaco J.M. et al.Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2.Nat. Genet. 2011; 43: 539-546Crossref PubMed Scopus (190) Google Scholar, 2Green D.M. Collaco J.M. McDougal K.E. Naughton K.M. Blackman S.M. Cutting G.R. Heritability of respiratory infection with Pseudomonas aeruginosa in cystic fibrosis.J. Pediatr. 2012; 161: 290-295.e1Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar, 3Emond M.J. Louie T. Emerson J. Zhao W. Mathias R.A. Knowles M.R. Wright F.A. Rieder M.J. Tabor H.K. Nickerson D.A. et al.National Heart, Lung, and Blood Institute (NHLBI) GO Exome Sequencing ProjectLung GOExome sequencing of extreme phenotypes identifies DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic fibrosis.Nat. Genet. 2012; 44: 886-889Crossref PubMed Scopus (170) Google Scholar, 4Li W. Soave D. Miller M.R. Keenan K. Lin F. Gong J. Chiang T. Stephenson A.L. Durie P. Rommens J. et al.Unraveling the complex genetic model for cystic fibrosis: pleiotropic effects of modifier genes on early cystic fibrosis-related morbidities.Hum. Genet. 2014; 133: 151-161Crossref PubMed Scopus (82) Google Scholar, 5Sun L. Rommens J.M. Corvol H. Li W. Li X. Chiang T.A. Lin F. Dorfman R. Busson P.F. Parekh R.V. et al.Multiple apical plasma membrane constituents are associated with susceptibility to meconium ileus in individuals with cystic fibrosis.Nat. Genet. 2012; 44: 562-569Crossref PubMed Scopus (150) Google Scholar but GWASs for CF are limited by numbers of subjects compared to common diseases, where tens of thousands of subjects have been used to identify pathophysiologically relevant pathways.6Okada Y. Wu D. Trynka G. Raj T. Terao C. Ikari K. Kochi Y. Ohmura K. Suzuki A. Yoshida S. et al.RACI consortiumGARNET consortiumGenetics of rheumatoid arthritis contributes to biology and drug discovery.Nature. 2014; 506: 376-381Crossref PubMed Scopus (1418) Google Scholar, 7Bønnelykke K. Matheson M.C. Pers T.H. Granell R. Strachan D.P. Alves A.C. Linneberg A. Curtin J.A. Warrington N.M. Standl M. et al.Australian Asthma Genetics Consortium (AAGC)EArly Genetics and Lifecourse Epidemiology (EAGLE) ConsortiumMeta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization.Nat. Genet. 2013; 45: 902-906Crossref PubMed Scopus (190) Google Scholar, 8Jostins L. Ripke S. Weersma R.K. Duerr R.H. McGovern D.P. Hui K.Y. Lee J.C. Schumm L.P. Sharma Y. Anderson C.A. et al.International IBD Genetics Consortium (IIBDGC)Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.Nature. 2012; 491: 119-124Crossref PubMed Scopus (3230) Google Scholar Studies of gene expression provide an alternative approach to identify gene modifiers.9Cookson W. Liang L. Abecasis G. Moffatt M. Lathrop M. Mapping complex disease traits with global gene expression.Nat. Rev. Genet. 2009; 10: 184-194Crossref PubMed Scopus (612) Google Scholar, 10Emilsson V. Thorleifsson G. Zhang B. Leonardson A.S. Zink F. Zhu J. Carlson S. Helgason A. Walters G.B. Gunnarsdottir S. et al.Genetics of gene expression and its effect on disease.Nature. 2008; 452: 423-428Crossref PubMed Scopus (1007) Google Scholar, 11Nica A.C. Montgomery S.B. Dimas A.S. Stranger B.E. Beazley C. Barroso I. Dermitzakis E.T. Candidate causal regulatory effects by integration of expression QTLs with complex trait genetic associations.PLoS Genet. 2010; 6: e1000895Crossref PubMed Scopus (313) Google Scholar Based upon the established utility of gene expression studies in lymphoblastoid cell lines (LCLs),12Nicolae D.L. Gamazon E. Zhang W. Duan S. Dolan M.E. Cox N.J. Trait-associated SNPs are more likely to be eQTLs: annotation to enhance discovery from GWAS.PLoS Genet. 2010; 6: e1000888Crossref PubMed Scopus (910) Google Scholar, 13Stranger B.E. Forrest M.S. Dunning M. Ingle C.E. Beazley C. Thorne N. Redon R. Bird C.P. de Grassi A. Lee C. et al.Relative impact of nucleotide and copy number variation on gene expression phenotypes.Science. 2007; 315: 848-853Crossref PubMed Scopus (1347) Google Scholar, 14Zhang W. Duan S. Kistner E.O. Bleibel W.K. Huang R.S. Clark T.A. Chen T.X. Schweitzer A.C. Blume J.E. Cox N.J. Dolan M.E. Evaluation of genetic variation contributing to differences in gene expression between populations.Am. J. Hum. Genet. 2008; 82: 631-640Abstract Full Text Full Text PDF PubMed Scopus (157) Google Scholar global gene expression was measured from LCLs of a highly phenotyped CF cohort previously used for GWAS analysis1Wright F.A. Strug L.J. Doshi V.K. Commander C.W. Blackman S.M. Sun L. Berthiaume Y. Cutler D. Cojocaru A. Collaco J.M. et al.Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2.Nat. Genet. 2011; 43: 539-546Crossref PubMed Scopus (190) Google Scholar and analyzed for association with three distinct CF phenotypes: lung disease severity, age of onset of persistent Pseudomonas aeruginosa (P. aeruginosa) pulmonary infection, and meconium ileus (MI [MIM 614665]) at birth (Table 1; Figure S1).Table 1Characteristics of Subject Population for PhenotypesStudy GroupConsortium Lung Phenotype (Primary Analysis)aSubjects were classified as having either severe or mild lung disease, as defined by the quantitative Consortium lung phenotype (KNoRMA) value of <0.3 or >0.3, respectively.18Age of Onset of Persistent Pseudomonas aeruginosaMeconium Ileus (MI)Size of PopulationAge at Enrollment (year)No. Males (%)No. EuropeanbBased on self-identified ancestry and principal components analysis via SNP genotypes. (%)Persistent Culture PositivecData were obtained at the encounter level (each clinic visit) from the Cystic Fibrosis Foundation (CFF) Patient Registry. Persistent is defined as cultured P. aeruginosa in respiratory cultures 2 years in a row, or 2 out of 3 years, unless subjects had at least 5 consecutive years of negative cultures after meeting minimal criteria (2 out of 3 years of positive cultures). Subjects who were above age 7 needed to have a negative culture before the first positive culture to be included into the analysis.28 There were 14 severe and 30 mild subjects who were negative for P. aeruginosa at last culture. (%)Age of Onset (year)Presence of MIdSubjects were confirmed to have MI if a diagnosis at birth was supported by source documents, such as the original surgical or medical report, detailed clinical or admissions note, or verbal confirmation from the subject or the parent with documentation of an abdominal scar. Subjects were removed from the analysis if MI could not be confirmed or if the diagnosis was unclear or unknown. (%)Mean ± SDRangeMean ± SDRangeSevere31716.5 ± 4.68–25157 (49.5)317 (100)208 of 222 (93.7)5.2 ± 4.30.6–1952 of 301 (17.3)Mild43728.0 ± 9.915–58221 (50.5)437 (100)203 of 233 (87.1)16.8 ± 10.30.6–5754 of 405 (13.3)ePresence of MI was 17.6% (36 of 205) for subjects enrolled at 15–25 years of age.Total754455706a Subjects were classified as having either severe or mild lung disease, as defined by the quantitative Consortium lung phenotype (KNoRMA) value of <0.3 or >0.3, respectively.18Taylor C. Commander C.W. Collaco J.M. Strug L.J. Li W. Wright F.A. Webel A.D. Pace R.G. Stonebraker J.R. Naughton K. et al.A novel lung disease phenotype adjusted for mortality attrition for cystic fibrosis genetic modifier studies.Pediatr. Pulmonol. 2011; 46: 857-869Crossref PubMed Scopus (41) Google Scholarb Based on self-identified ancestry and principal components analysis via SNP genotypes.c Data were obtained at the encounter level (each clinic visit) from the Cystic Fibrosis Foundation (CFF) Patient Registry. Persistent is defined as cultured P. aeruginosa in respiratory cultures 2 years in a row, or 2 out of 3 years, unless subjects had at least 5 consecutive years of negative cultures after meeting minimal criteria (2 out of 3 years of positive cultures). Subjects who were above age 7 needed to have a negative culture before the first positive culture to be included into the analysis.28Pittman J.E. Calloway E.H. Kiser M. Yeatts J. Davis S.D. Drumm M.L. Schechter M.S. Leigh M.W. Emond M. Van Rie A. Knowles M.R. Age of Pseudomonas aeruginosa acquisition and subsequent severity of cystic fibrosis lung disease.Pediatr. Pulmonol. 2011; 46: 497-504PubMed Google Scholar There were 14 severe and 30 mild subjects who were negative for P. aeruginosa at last culture.d Subjects were confirmed to have MI if a diagnosis at birth was supported by source documents, such as the original surgical or medical report, detailed clinical or admissions note, or verbal confirmation from the subject or the parent with documentation of an abdominal scar. Subjects were removed from the analysis if MI could not be confirmed or if the diagnosis was unclear or unknown.e Presence of MI was 17.6% (36 of 205) for subjects enrolled at 15–25 years of age. Open table in a new tab Affymetrix Human Exon (1.0 ST) microarray data were collected from RNA isolated from 754 LCLs selected from a cohort of 1,137 samples from CFTR (MIM 602421) p.Phe508del European individuals homozygous for the mutation (chr7: 98,809–98,811 delCTT; RefSeq accession number NG_016465.3; c.1521_1523delCTT). These CF-affected individuals were originally obtained for the Genetic Modifiers in CF Lung Disease Study where a GWAS had been performed1Wright F.A. Strug L.J. Doshi V.K. Commander C.W. Blackman S.M. Sun L. Berthiaume Y. Cutler D. Cojocaru A. Collaco J.M. et al.Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2.Nat. Genet. 2011; 43: 539-546Crossref PubMed Scopus (190) Google Scholar (Figure S2). Considerable efforts were taken to ensure that high-quality microarray data were utilized and that interpretation would not be confused by known effect of SNPs on probe hybridization kinetics (Figure S2). For the highly polymorphic HLA region, probe set filtering removed 438 of the 797 probe sets. However, because of the concern that probe set filtering might not have been adequate in HLA genes, additional analysis was performed to identify HLA genes whose expression values were probably affected by probe set binding (Figure S3). As a result of this analysis, HLA-DRB1 (MIM 142857) expression values were removed from subsequent analysis. The study was approved by the biomedical institutional review board of the University of North Carolina and the institutional review board of each participating institution. CF-affected individuals and their parents (if they were a minor) provided written informed consent. Linear regression was utilized to establish association of gene expression with phenotypes. Gene expression values meeting a minimal threshold of expression above 6.03 (on the Affymetrix RMA standard log2 scale) were utilized, based on the 95th percentile of mean “expression” in females for genes on the Y chromosome, because this threshold was considered to reliably represent true signal above background. All genes meeting this criterion (12,033 out of 17,868 annotated genes; 67.3%) were included in the linear regression analysis, including genes whose probes overlaid SNPs with high minor allele frequency (MAF), but these genes were “flagged” so that potentially important interpretive issues could be considered later. The covariates used for all analyses are listed in Table S1. The genotype PCs used as covariates were calculated with Eigenstrat15Price A.L. Patterson N.J. Plenge R.M. Weinblatt M.E. Shadick N.A. Reich D. Principal components analysis corrects for stratification in genome-wide association studies.Nat. Genet. 2006; 38: 904-909Crossref PubMed Scopus (6831) Google Scholar and available genotype data from the previously conducted GWASs.1Wright F.A. Strug L.J. Doshi V.K. Commander C.W. Blackman S.M. Sun L. Berthiaume Y. Cutler D. Cojocaru A. Collaco J.M. et al.Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2.Nat. Genet. 2011; 43: 539-546Crossref PubMed Scopus (190) Google Scholar The surrogate variables of gene expression data were calculated with the “sva” package in Bioconductor in R.16Leek J.T. Johnson W.E. Parker H.S. Jaffe A.E. Storey J.D. The sva package for removing batch effects and other unwanted variation in high-throughput experiments.Bioinformatics. 2012; 28: 882-883Crossref PubMed Scopus (2291) Google Scholar The Q-Q plots for all three phenotypes suggested that the covariates included were appropriate to control for population stratification or technical factors that could potentially lead to false positives (Figure S4). The expression of lysophosphatidic acid receptor 6 (LPAR6 [MIM 278150]) achieved transcriptome-wide significance for association with lung disease (false discovery rate q value = 0.0006, p value = 5.35 × 10−8), using both standard and alternative probe annotation (ANNMAP, formerly known as X:MAP),17Yates T. Okoniewski M.J. Miller C.J. X:Map: annotation and visualization of genome structure for Affymetrix exon array analysis.Nucleic Acids Res. 2008; 36: D780-D786Crossref PubMed Scopus (53) Google Scholar with higher levels of LPAR6 being associated with worse lung function. Array-based LPAR6 expression was technically validated by TaqMan quantitative real-time PCR (p < 0.0001 between 36 low-expressing and 40 high-expressing LCL samples from CF-affected individuals). CHMP4C (p = 1.05 × 10−5 [MIM 610899]), SSBP2 (p = 2.60 × 10−5 [MIM 607389]), and P2RX4 (p = 8.03 × 10−5 [MIM 600846]) were suggestive for association (Table S2; Figure S5; see Table S5 for complete list). As explicitly accounted for by the Consortium lung phenotype,18Taylor C. Commander C.W. Collaco J.M. Strug L.J. Li W. Wright F.A. Webel A.D. Pace R.G. Stonebraker J.R. Naughton K. et al.A novel lung disease phenotype adjusted for mortality attrition for cystic fibrosis genetic modifier studies.Pediatr. Pulmonol. 2011; 46: 857-869Crossref PubMed Scopus (41) Google Scholar older surviving CF-affected individuals have milder lung disease, reflecting high mortality in CF (Table 1). To investigate a possible relationship between age and gene expression in the CF cohort, but unrelated to CF lung disease, we examined three large external studies of LCL gene expression. These included a childhood asthma (MIM 600807) cohort evaluated on the Affymetrix platform,19Liang L. Morar N. Dixon A.L. Lathrop G.M. Abecasis G.R. Moffatt M.F. Cookson W.O. A cross-platform analysis of 14,177 expression quantitative trait loci derived from lymphoblastoid cell lines.Genome Res. 2013; 23: 716-726Crossref PubMed Scopus (108) Google Scholar available data from the Cholesterol and Pharmacogenomics (CAP) trial (available on ArrayExpress),20Yu C.Y. Theusch E. Lo K. Mangravite L.M. Naidoo D. Kutilova M. Medina M.W. HNRNPA1 regulates HMGCR alternative splicing and modulates cellular cholesterol metabolism.Hum. Mol. Genet. 2014; 23: 319-332Crossref PubMed Scopus (46) Google Scholar and the Multiple Tissue Human Expression Resource (MuTHER) study.21Glass D. Viñuela A. Davies M.N. Ramasamy A. Parts L. Knowles D. Brown A.A. Hedman A.K. Small K.S. Buil A. et al.UK Brain Expression consortiumMuTHER consortiumGene expression changes with age in skin, adipose tissue, blood and brain.Genome Biol. 2013; 14: R75Crossref PubMed Scopus (189) Google Scholar No correspondence emerged between differentially expressed genes for the Consortium lung phenotype and those associated with age in these three non-CF populations (Figure S6), although LPAR6 was nominally associated with age (not corrected for multiple comparison) in older women (age ∼59 years) in the MuTHER study.21Glass D. Viñuela A. Davies M.N. Ramasamy A. Parts L. Knowles D. Brown A.A. Hedman A.K. Small K.S. Buil A. et al.UK Brain Expression consortiumMuTHER consortiumGene expression changes with age in skin, adipose tissue, blood and brain.Genome Biol. 2013; 14: R75Crossref PubMed Scopus (189) Google Scholar Consequently, we conclude that the associations seen in our study reflect CF lung disease severity and not aging. Rigorous “pathway” (gene set) analysis was conducted via a permutation-based approach (Significance Analysis of Function and Expression; SAFE), which accounts for gene expression correlation structures and allows testing of both standard and custom-derived pathways.22Barry W.T. Nobel A.B. Wright F.A. Significance analysis of functional categories in gene expression studies: a structured permutation approach.Bioinformatics. 2005; 21: 1943-1949Crossref PubMed Scopus (253) Google Scholar Pathway analysis was conducted by SAFE in R (v.3.0) and annotation databases (available at Bioconductor) hugene10stprobeset.db and GO.db (Gene Ontology annotation maps). Multiple pathways with q values < 0.15 were found to associate with lung disease severity (Table 2; Table S6, tab A). Of the 35 pathways listed (Table 2), 16 were related to the endomembrane system for synthesis and post-translational modification of membrane proteins (membranes, vesicle traffic, and Golgi/endoplasmic reticulum [ER]) and two pathways were related to ER stress response, which also could represent a subset of endomembrane processes. Of the 11 Gene Ontology (GO) Cellular Component pathways, 7 contained HLA class I genes, and custom-derived pathways consisting exclusively of HLA genes were also highly significant (Table 2). Importantly, although the HLA genes clearly contributed to the significance of the endomembrane pathways, these same pathways also contained TTC35 (Table 2 [MIM 607722]) and TMEM85 (Table S6, tab A; p value = 0.06), which are the human homologs of yeast genes EMC2 and EMC4, respectively, known to modulate yeast homolog of p.Phe508del processing.23Louie R.J. Guo J. Rodgers J.W. White R. Shah N. Pagant S. Kim P. Livstone M. Dolinski K. McKinney B.A. et al.A yeast phenomic model for the gene interaction network modulating CFTR-ΔF508 protein biogenesis.Genome Med. 2012; 4: 103Crossref PubMed Scopus (55) Google Scholar MetaMiner Cystic Fibrosis Specific Pathways not containing HLA genes also supported association with p.Phe508del processing (Table 2). We conclude that three important pathophysiological signals have emerged: HLA class I, p.Phe508del processing, and the ER stress response. The significance of the miR21 (miRNA-21 [MIM 611020]) pathway is also relevant given the expanding role of this microRNA (miRNA) in pulmonary biology.24Kumarswamy R. Volkmann I. Thum T. Regulation and function of miRNA-21 in health and disease.RNA Biol. 2011; 8: 706-713Crossref PubMed Scopus (444) Google Scholar Most pathways trended in the “up” direction (increased expression of genes in the pathways associated with milder lung disease), with two pathways (annotated to germ cell nuclei) trending “down.”Table 2Gene Expression Pathways Significantly Associated with Consortium Lung PhenotypePathwayGenesStatisticsIDNameNumber↑aNumber of genes in pathway with increased expression.↓bNumber of genes in pathway with decreased expression.TrendcUp (increased) or down (decreased) differential expression of genes in the pathways associated with milder lung disease. Two-sided indicates pathways that contained both increased and decreased differentially expressed genes that contributed significantly to the signal.p ValuedDetermined by 10,000 permutations in the SAFE package.22q ValueeBenjamini-Hochberg false-discovery for pathways testing within each pathway set; q values < 0.15 were included.Genes with Gene-Level p Value < 0.05 (Ordered by p Value)fSee Table S6 (tab A) for the inclusive list of genes for these pathways; “none” indicates that no individual genes within the pathway had a p value less than 0.05; see Table S5 for gene MIM numbers.GO Cellular Component Pathways0001673male germ cell nucleus14014down0.00010.0164TNP1; REC8; TCFL50012507ER to Golgi transport vesicle membrane25232up0.00030.0481HLA-E; MCFD2; TMED7; HLA-F0043073germ cell nucleus17116down0.00040.0442TNP1; REC8; TCFL50042470;0048770melanosome; pigment granule785226up0.00070.0582SLC3A2; TPP1; CTSD; ANXA2; STOM; HSPA5; BSG0030134ER to Golgi transport vesicle29254up0.00110.0737HLA-E; MCFD2; TMED7; HLA-F0030176integral to endoplasmic reticulum membrane856421up0.00240.1181TTC35; HLA-E; EDEM1; TAP1; SELS; HLA-F; HSPA5; MMGT10031301integral to organelle membrane17111358up0.00260.1181TTC35; HLA-E; EDEM1; TAP1; SELS; ST6GALNAC6; HLA-F; A4GALT; ARMCX3; P2RX7; LARGE; HSPA5; MMGT10000421autophagic vacuole membrane13112up0.00280.1181WIPI1; ATG9A0031227intrinsic to endoplasmic reticulum membrane957025up0.00310.1181TTC35; HLA-E; EDEM1; TAP1; SELS; HLA-F; HSPA5; MMGT10031300intrinsic to organelle membrane18412163up0.00360.1231TTC35; HLA-E; EDEM1; TAP1; SELS; ST6GALNAC6; HLA-F; A4GALT; ARMCX3; P2RX7; LARGE; HSPA5; MMGT10030658transport vesicle membrane493316up0.00390.1231HLA-E; MCFD2; TMED7; HLA-F; NCALDGO Biological Process Pathways0006518peptide metabolic process644618up0.00010.0837GSTK1; DNPEP; PSEN2; TPP10072384organelle transport along microtubule24213up0.00010.0837PRKCZ; COPG0006925inflammatory cell apoptotic process10100up0.00030.1107none0006944cellular membrane fusion614219up0.00030.1107CD9; PLDN; ANXA2; BET10007030golgi organization382810up0.00030.1107GCC2; BHLHA15; GOLGB1; PLK3; COG1; TMED20043603cellular amide metabolic process1016536up0.00030.1107GSTK1; DNPEP; PSEN2; TPP1; PRKCD0034067protein localization to Golgi apparatus14131up0.00040.1166GOLGA4; GCC2; ATG9A0045684positive regulation of epidermis development11101up0.00040.1166noneGO Molecular Function Pathways0050839cell adhesion molecule binding331518two sided0.00040.1181P2RX4; MLLT4; CD1D;gFor the two-sided “Trend,” these genes have a “down” trend. CTNNA1; PVRL1gFor the two-sided “Trend,” these genes have a “down” trend.0042287MHC protein binding1596two sided0.00060.1191TAP1; LAG3; MARCH8MSigDB PathwaysATAAGCT.MIR.21814536two sided0.00010.0387BAHD1; BTBD3;gFor the two-sided “Trend,” these genes have a “down” trend. C5orf41; STK40; UBR3; NF2;gFor the two-sided “Trend,” these genes have a “down” trend. SSFA2; JAG1; PPARA; PELI1; RHOB; CREBL2V.HMGIY_Q61587088two sided0.00060.1499ZNF675;gFor the two-sided “Trend,” these genes have a “down” trend. LMO4; TNFSF11;gFor the two-sided “Trend,” these genes have a “down” trend. PLAGL2; POLD3;gFor the two-sided “Trend,” these genes have a “down” trend. SLC7A1; UBE2E2;gFor the two-sided “Trend,” these genes have a “down” trend. TAZ; UBR3; MRC2;gFor the two-sided “Trend,” these genes have a “down” trend. TNFSF4; IKZF2gFor the two-sided “Trend,” these genes have a “down” trend.MetaMiner Cystic Fibrosis Specific PathwayshMetaMiner CF Specific Pathways represent a version of Thomson Reuters’ (formerly GeneGo) MetaDiscovery suite that is enriched with content specific for cystic fibrosis.cholesterol and sphingolipids transport/recycling to plasma membrane in lung (normal and CF)1495two sided0.00360.0597ABCG1gFor the two-sided “Trend,” these genes have a “down” trend.normal wtCFTR traffic/sorting endosome formation14113up0.00520.0621noneF508-CFTR traffic/ER-to-Golgi in CF; Normal wtCFTR traffic/ER-to-Golgi22202up0.00750.0621COPG; COPZ2mucin expression in CF via TLRs, EGFR signaling pathways483414up0.01160.0770JUN; PRKCDPFAM Pathways00035double-stranded RNA binding motif17215down0.00010.0135STRBP; STAU207716basic region leucine zipper1174two sided0.00020.0276DDIT3; CREBL2; CEBPB03953tubulin C-terminal domain15213down0.00090.0804TUBB2BCF Relevant Custom PathwaysER stress response16912742up0.00050.0106DNAJB9; EDEM1; CISD2; TANK; DDIT3; SERP1; FDPS; LONP1; NANS; SSR4; JUN; GADD45A; LY9; PGM3; HSPA5; ARF4; IER3IP1; BTG2; CEBPB; CNIH; MANF; PDIA6XBP1 target genes13103two sided0.00790.1165DNAJB9; EDEM1; SERP1; PDIA6HLA-Specific Pathwaysclass I330up0.02210.0261HLA-E; HLA-Fclass II871up0.08680.0580noneclass I and class II11101up0.02990.0261HLA-E; HLA-FPathways limited to those with ≥10 but ≤200 genes. SAFE analysis utilized 10,000 permutations to establish significance thresholds. CF Relevant Custom Pathways developed primarily as described for mice46Saini Y. Dang H. Livraghi-Butrico A. Kelly E.J. Jones L.C. O’Neal W.K. Boucher R.C. Gene expression in whole lung and pulmonary macrophages reflects the dynamic pathology associated with airway surface dehydration.BMC Genomics. 2014; 15: 726Crossref PubMed Scopus (34) Google Scholar using human gene counterparts (Table S8).a Number of genes in pathway with increased expression.b Number of genes in pathway with decreased expression.c Up (increased) or down (decreased) differential expression of genes in the pathways associated with milder lung disease. Two-sided indicates pathways that contained both increased and decreased differentially expressed genes that contributed significantly to the signal.d Determined by 10,000 permutations in the SAFE package.22Barry W.T. Nobel A.B. Wright F.A. Significance analysis of functional categories in gene expression studies: a structured permutation approach.Bioinformatics. 2005; 21: 1943-1949Crossref PubMed Scopus (253) Google Scholare Benjamini-Hochberg false-discovery for pathways testing within each pathway set; q values < 0.15 were included.f See Table S6 (tab A) for the inclusive list of genes for these pathways; “none” indicates that no individual genes within the pathway had a p value less than 0.05; see Table S5 for gene MIM numbers.g For the two-sided “Trend,” these genes have a “down” trend.h MetaMiner CF Specific Pathways represent a version of Thomson Reuters’ (formerly GeneGo) MetaDiscovery suite that is enriched with content specific for cystic fibrosis. Open table in a new tab Pathways limited to those with ≥10 but ≤200 genes. SAFE analysis utilized 10,000 permutations to establish s
DA - 2015/2//
PY - 2015/2//
DO - 10.1016/J.AJHG.2014.12.022
VL - 96
IS - 2
SP - 318-328
J2 - The American Journal of Human Genetics
LA - en
OP -
SN - 0002-9297
UR - http://dx.doi.org/10.1016/J.AJHG.2014.12.022
DB - Crossref
ER -
TY - JOUR
TI - EVALUATING THE ECO-GEOMORPHOLOGICAL CONDITION OF RESTORED STREAMS USING VISUAL ASSESSMENT AND MACROINVERTEBRATE METRICS
AU - Doll, Barbara A.
AU - Jennings, Gregory D.
AU - Spooner, Jean
AU - Penrose, David L.
AU - Usset, Joseph L.
T2 - JOURNAL OF THE AMERICAN WATER RESOURCES ASSOCIATION
AB - Abstract The Stream Performance Assessment ( SPA ), a new rapid assessment method, was applied to 93 restored, 21 impaired, 29 reference, and 13 reference streams with some incision throughout North Carolina. Principal component analysis ( PCA ) indicated restored streams align more closely with reference streams rather than impaired streams. Further, PCA ‐based factor analysis revealed restored streams were similar to reference streams in terms of morphologic condition, but exhibited a greater range of scores relative to aquatic habitat and bedform. Macroinvertebrate sampling and GIS watershed analyses were conducted on 84 restored streams. SPA and watershed data were compared to Ephemeroptera, Plecoptera, and Trichoptera ( EPT ) taxa to determine which factors indicate stream health. SPA and watershed factors were used in least squares, ridge, and principal component regression ( PCR ) to develop a prediction model for EPT taxa. All three methods produced reasonable predictions for EPT taxa. Cross‐validation indicated ridge regression resulted in the lowest prediction error. The ridge model was then used to predict EPT taxa numbers for 21 impaired and 25 reference streams in addition to the 84 restored streams. Statistical comparisons of the predicted scores indicated urban streams (>10% impervious watershed cover) have lower expected numbers of EPT taxa. Rural restored streams have macroinvertebrate metric scores similar to those predicted for rural reference streams.
DA - 2015/2//
PY - 2015/2//
DO - 10.1111/jawr.12233
VL - 51
IS - 1
SP - 68-83
SN - 1752-1688
KW - rivers
KW - streams
KW - restoration
KW - macroinvertebrates
KW - watershed
KW - stream assessment
ER -
TY - JOUR
TI - Development of prediction equations to estimate the apparent digestible energy content of lipids when fed to lactating sows
AU - Rosero, D. S.
AU - Odle, J.
AU - Arellano, C.
AU - Boyd, R. D.
AU - Heugten, E.
T2 - JOURNAL OF ANIMAL SCIENCE
AB - Two studies were conducted 1) to determine the effects of free fatty acid (FFA) concentrations and the degree of saturation of lipids (unsaturated to saturated fatty acids ratio [U:S]) on apparent total tract digestibility (ATTD) and DE content of lipids and 2) to derive prediction equations to estimate the DE content of lipids when added to lactating sow diets. In Exp. 1, 85 lactating sows were assigned randomly to a 4 × 5 factorial arrangement of treatments plus a control diet with no added lipid. Factors included 1) FFA concentrations of 0, 18, 36, and 54% and 2) U:S of 2.0, 2.8, 3.5, 4.2, and 4.9. Diets were corn–soybean meal based and lipid was supplemented at 6%. Concentrations of FFA and U:S were obtained by blending 4 lipid sources: choice white grease (CWG; FFA = 0.3% and U:S = 2.0), soybean oil (FFA = 0.1% and U:S = 5.5), CWG acid oil (FFA = 57.8% and U:S = 2.1), and soybean–cottonseed acid oil (FFA = 67.5% and U:S = 3.8). Titanium dioxide was added to diets (0.5%) as a digestibility marker. Treatments started on d 4 of lactation and fecal samples were collected after 6 d of adaptation to diets on a daily basis from d 10 to 13. The ATTD of added lipid and DE content of lipids were negatively affected (linear, P < 0.001) with increasing FFA concentrations, but negative effects were less pronounced with increasing U:S (interaction, P < 0.05). Coefficients of ATTD for the added lipid and DE content of lipids increased with increasing U:S (quadratic, P = 0.001), but these improvements were less pronounced when the FFA concentration was less than 36%. Digestible energy content of added lipid was described by DE (kcal/kg) = [8,381 – (80.6 × FFA) + (0.4 × FFA2) + (248.8 × U:S) – (28.1 × U:S2) + (12.8 × FFA × U:S)] (R2 = 0.74). This prediction equation was validated in Exp. 2, in which 24 lactating sows were fed diets supplemented with 6% of either an animal–vegetable blend (A-V; FFA = 14.5% and U:S = 2.3) or CWG (FFA = 3.7% and U:S = 1.5) plus a control diet with no added lipids. Digestible energy content of A-V (8,317 and 8,127 kcal/kg for measured and predicted values, respectively) and CWG (8,452 and 8,468 kcal/kg for measured and predicted values, respectively) were accurately estimated using the proposed equation. The proposed equation involving FFA concentration and U:S resulted in highly accurate estimations of DE content (relative error, +0.2 to –2.3%) of commercial sources of lipids for lactating sows.
DA - 2015/3//
PY - 2015/3//
DO - 10.2527/jas.2014-8402
VL - 93
IS - 3
SP - 1165-1176
SN - 1525-3163
KW - digestibility
KW - free fatty acids
KW - lactating sow
KW - lipid saturation
KW - prediction equation
ER -
TY - JOUR
TI - Comparison of toxicity values across zebrafish early life stages and mammalian studies: Implications for chemical testing
AU - Ducharme, N. A.
AU - Reif, D. M.
AU - Gustafsson, J. A.
AU - Bondesson, M.
T2 - Reproductive Toxicology (Elmsford, N.Y.)
DA - 2015///
PY - 2015///
VL - 55
SP - 3-10
ER -
TY - JOUR
TI - Comparing Bridge Deck Runoff and Stormwater Control Measure Quality in North Carolina
AU - Winston, Ryan J.
AU - Lauffer, Matthew S.
AU - Narayanaswamy, Karthik
AU - McDaniel, Andrew H.
AU - Lipscomb, Brian S.
AU - Nice, Alex J.
AU - Hunt, William F.
T2 - Journal of Environmental Engineering
AB - Bridge deck runoff sometimes directly discharges through deck drains to water bodies. As such, the runoff is usually not treated; however, recent pressures have led Departments of Transportation to install closed pipe drainage systems beneath bridges to deliver stormwater to a stormwater control measure (SCM). This can be costly both in terms of up-front and long-term maintenance capital. This study compared bridge runoff concentrations of nutrients, sediment, and heavy metals to effluent concentrations from six commonly used SCMs. Runoff quality samples from 15 bridges in North Carolina were collected and compared to those from 41 different SCMs across North Carolina. The SCMs examined in this study were permeable friction course (PFC) overlays, wet retention ponds (WP), bioretention cells (BRC), vegetated filter strips (VFS), constructed stormwater wetlands (CSW), and grassed swales (GS). Bridge deck runoff concentrations were not statistically different from SCM effluent concentrations for total nitrogen (TN). For total phosphorus (TP), all SCMs produced effluent concentrations lower than bridge runoff concentrations, although only PFC, BRC, and WP did so significantly. For total suspended solids (TSS), median effluent concentrations from the SCMs were significantly and substantially lower (a difference of more than 15 mg/L) than those from bridges. Comparison against water quality threshold concentrations developed for North Carolina suggested that BRC and WP were best for TN treatment and that PFC, WP, and BRC were appropriate for TP treatment. For TSS, all six SCMs were capable of improving the bridge runoff. Similar results were observed for copper, lead, and zinc; BRC, GS, and CSW were able to reduce total metals concentrations significantly. Dissolved metal concentrations appeared difficult to reduce with current SCM technology. These results suggest that for certain pollutants, treatment of bridge runoff may yield improvement. However, the appropriateness of installing SCMs to treat bridge deck runoff must account for the increased cost of closed pipe drainage systems beneath bridges and limited space in the right-of-way and weighed against the relative ease of retrofitting stormwater treatment infrastructure into other transportation corridors.
DA - 2015/1//
PY - 2015/1//
DO - 10.1061/(ASCE)EE.1943-7870.0000864
VL - 141
IS - 1
SP - 04014045
J2 - J. Environ. Eng.
LA - en
OP -
SN - 0733-9372 1943-7870
UR - http://dx.doi.org/10.1061/(ASCE)EE.1943-7870.0000864
DB - Crossref
KW - Highway runoff
KW - Road runoff
KW - Nutrient
KW - Sediment
KW - Heavy metals
KW - SCM
KW - BMP
KW - Urban
KW - Water quality
KW - Bridges
ER -
TY - JOUR
TI - Assessment of critical exposure and outcome windows in time-to-event analysis with application to air pollution and preterm birth study
AU - Chang, Howard H.
AU - Warren, Joshua L.
AU - Darrow, Lnydsey A.
AU - Reich, Brian J.
AU - Waller, Lance A.
T2 - BIOSTATISTICS
AB - In reproductive epidemiology, there is a growing interest to examine associations between air pollution exposure during pregnancy and the risk of preterm birth (PTB). One important research objective is to identify critical periods of exposure and estimate the associated effects at different stages of pregnancy. However, population studies have reported inconsistent findings. This may be due to limitations from the standard analytic approach of treating PTB as a binary outcome without considering time-varying exposures together over the course of pregnancy. To address this research gap, we present a Bayesian hierarchical model for conducting a comprehensive examination of gestational air pollution exposure by estimating the joint effects of weekly exposures during different vulnerable periods. Our model also treats PTB as a time-to-event outcome to address the challenge of different exposure lengths among ongoing pregnancies. The proposed model is applied to a dataset of geocoded birth records in the Atlanta metropolitan area between 1999–2005 to examine the risk of PTB associated with gestational exposure to ambient fine particulate matter |$\lt 2.5\,{\rm \mu}$|m in aerodynamic diameter (PM|$_{2.5}$|). We find positive associations between PM|$_{2.5}$| exposure during early and mid-pregnancy, and evidence that associations are stronger for PTBs occurring around week 30.
DA - 2015/7//
PY - 2015/7//
DO - 10.1093/biostatistics/kxu060
VL - 16
IS - 3
SP - 509-521
SN - 1468-4357
KW - Air pollution
KW - Fine particulate matter
KW - Joint effects
KW - Preterm birth
KW - Time-dependent exposure
KW - Time-to-event model
KW - Time-varying effect
ER -
TY - JOUR
TI - A fast EM algorithm for fitting joint models of a binary response and multiple longitudinal covariates subject to detection limits
AU - Bernhardt, Paul W.
AU - Zhang, Daowen
AU - Wang, Huixia Judy
T2 - COMPUTATIONAL STATISTICS & DATA ANALYSIS
AB - Joint modeling techniques have become a popular strategy for studying the association between a response and one or more longitudinal covariates. Motivated by the GenIMS study, where it is of interest to model the event of survival using censored longitudinal biomarkers, a joint model is proposed for describing the relationship between a binary outcome and multiple longitudinal covariates subject to detection limits. A fast, approximate EM algorithm is developed that reduces the dimension of integration in the E-step of the algorithm to one, regardless of the number of random effects in the joint model. Numerical studies demonstrate that the proposed approximate EM algorithm leads to satisfactory parameter and variance estimates in situations with and without censoring on the longitudinal covariates. The approximate EM algorithm is applied to analyze the GenIMS data set.
DA - 2015/5//
PY - 2015/5//
DO - 10.1016/j.csda.2014.11.011
VL - 85
SP - 37-53
SN - 1872-7352
KW - Detection limit
KW - EM algorithm
KW - Joint model
KW - Logistic regression
KW - Multiple longitudinal covariates
KW - Normal approximation
ER -
TY - JOUR
TI - The community ecology of pathogens: coinfection, coexistence and community composition
AU - Seabloom, Eric W.
AU - Borer, Elizabeth T.
AU - Gross, Kevin
AU - Kendig, Amy E.
AU - Lacroix, Christelle
AU - Mitchell, Charles E.
AU - Mordecai, Erin A.
AU - Power, Alison G.
T2 - ECOLOGY LETTERS
AB - Disease and community ecology share conceptual and theoretical lineages, and there has been a resurgence of interest in strengthening links between these fields. Building on recent syntheses focused on the effects of host community composition on single pathogen systems, we examine pathogen (microparasite) communities using a stochastic metacommunity model as a starting point to bridge community and disease ecology perspectives. Such models incorporate the effects of core community processes, such as ecological drift, selection and dispersal, but have not been extended to incorporate host-pathogen interactions, such as immunosuppression or synergistic mortality, that are central to disease ecology. We use a two-pathogen susceptible-infected (SI) model to fill these gaps in the metacommunity approach; however, SI models can be intractable for examining species-diverse, spatially structured systems. By placing disease into a framework developed for community ecology, our synthesis highlights areas ripe for progress, including a theoretical framework that incorporates host dynamics, spatial structuring and evolutionary processes, as well as the data needed to test the predictions of such a model. Our synthesis points the way for this framework and demonstrates that a deeper understanding of pathogen community dynamics will emerge from approaches working at the interface of disease and community ecology.
DA - 2015/4//
PY - 2015/4//
DO - 10.1111/ele.12418
VL - 18
IS - 4
SP - 401-415
SN - 1461-0248
KW - Coinfection
KW - community ecology
KW - disease ecology
KW - dispersal
KW - drift
KW - metacommunity
KW - metapopulation
KW - pathogen
KW - selection
KW - speciation
ER -
TY - JOUR
TI - Retrofitting Residential Streets with Stormwater Control Measures over Sandy Soils for Water Quality Improvement at the Catchment Scale
AU - Page, Jonathan L.
AU - Winston, Ryan J.
AU - Mayes, Dave B.
AU - Perrin, Christy A.
AU - Hunt, William F., III
T2 - JOURNAL OF ENVIRONMENTAL ENGINEERING
AB - Impervious cover (IC) has been shown to increase runoff volumes, peak discharges, and pollutant loads to streams, which can lead to degraded water quality and biological integrity. Stormwater control measures (SCMs) have been developed to mitigate the hydrologic and water quality impacts of urban areas and IC. This paired watershed study evaluated the impacts of multiple SCM retrofits on water quality at a catchment scale in a 0.53 ha urban residential drainage area. In February 2012, an in-street bioretention cell (BRC) retrofit, four permeable pavement parking stalls, and a tree filter device were installed to treat residential street runoff in Wilmington, North Carolina. In the retrofitted catchment, 94% of the directly connected impervious area (DCIA) and 91% of the total drainage area were retrofitted for water quality treatment. Underlying soils in the study area were sand. After the SCM retrofits were constructed, concentrations of total Kjeldahl nitrogen (TKN), total phosphorous (TP), total suspended solids (TSS), copper (Cu), lead (Pb), and zinc (Zn) significantly decreased by 62%, 38%, 82%, 62%, 89%, and 76%, respectively. Concentrations of dissolved pollutants [nitrate-nitrite-nitrogen (NO2,3-N), total ammoniacal nitrogen (TAN), and orthophosphate (O-PO43−)] did not change. Mass exports of TKN, TAN, O-PO43−, TP, TSS, Cu, Pb, and Zn significantly decreased by 79%, 60%, 54%, 72%, 91%, 54%, 88%, and 77%, respectively. Improvements in water quality were due to decreases in particulate and particulate-bound pollutant concentrations and loads. This study has shown that a limited number of SCMs installed within a street right-of-way can mitigate a substantial portion of the water quality impacts caused by existing residential development.
DA - 2015/4//
PY - 2015/4//
DO - 10.1061/(asce)ee.1943-7870.0000898
VL - 141
IS - 4
SP -
SN - 1943-7870
KW - Stormwater control measures
KW - Urban runoff
KW - Low-impact development
KW - Retrofit
KW - Right-of-way
KW - Green street
ER -
TY - JOUR
TI - Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways
AU - O'Dushlaine, C.
AU - Rossin, L.
AU - Lee, P. H.
AU - Duncan, L.
AU - Parikshak, N. N.
AU - Newhouse, S.
AU - Ripke, S.
AU - Neale, B. M.
AU - Purcell, S. M.
AU - Posthuma, D.
AU - Nurnberger, J. I.
AU - Lee, S. H.
AU - Faraone, S. V.
AU - Perlis, R. H.
AU - Mowry, B. J.
AU - Thapar, A.
AU - Goddard, M. E.
T2 - Nature Neuroscience
DA - 2015///
PY - 2015///
VL - 18
IS - 2
SP - 199-209
ER -
TY - JOUR
TI - Partially supervised spatiotemporal clustering for burglary crime series identification
AU - Reich, Brian J.
AU - Porter, Michael D.
T2 - JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES A-STATISTICS IN SOCIETY
AB - Summary Statistical clustering of criminal events can be used by crime analysts to create lists of potential suspects for an unsolved crime, to identify groups of crimes that may have been committed by the same individuals or group of individuals, for offender profiling and for predicting future events. We propose a Bayesian model-based clustering approach for criminal events. Our approach is semisupervised, because the offender is known for a subset of the events, and utilizes spatiotemporal crime locations as well as crime features describing the offender's modus operandi. The hierarchical model naturally handles complex features that are often seen in crime data, including missing data, interval-censored event times and a mix of discrete and continuous variables. In addition, our Bayesian model produces posterior clustering probabilities which allow analysts to act on model output only as warranted. We illustrate the approach by using a large data set of burglaries in 2009–2010 in Baltimore County, Maryland.
DA - 2015/2//
PY - 2015/2//
DO - 10.1111/rssa.12076
VL - 178
IS - 2
SP - 465-480
SN - 1467-985X
KW - Bayesian hierarchical model
KW - Crime linkage
KW - Markov chain Monte Carlo methods
KW - Model-based clustering
ER -
TY - JOUR
TI - Doubly robust learning for estimating individualized treatment with censored data
AU - Zhao, Y. Q.
AU - Zeng, D.
AU - Laber, E. B.
AU - Song, R.
AU - Yuan, M.
AU - Kosorok, M. R.
T2 - BIOMETRIKA
AB - Individualized treatment rules recommend treatments based on individual patient characteristics in order to maximize clinical benefit. When the clinical outcome of interest is survival time, estimation is often complicated by censoring. We develop nonparametric methods for estimating an optimal individualized treatment rule in the presence of censored data. To adjust for censoring, we propose a doubly robust estimator which requires correct specification of either the censoring model or survival model, but not both; the method is shown to be Fisher consistent when either model is correct. Furthermore, we establish the convergence rate of the expected survival under the estimated optimal individualized treatment rule to the expected survival under the optimal individualized treatment rule. We illustrate the proposed methods using simulation study and data from a Phase III clinical trial on non-small cell lung cancer.
DA - 2015/3//
PY - 2015/3//
DO - 10.1093/biomet/asu050
VL - 102
IS - 1
SP - 151-168
SN - 1464-3510
KW - Censored data
KW - Doubly robust estimator
KW - Individualized treatment rule
KW - Risk bound
KW - Support vector machine
ER -
TY - JOUR
TI - Domain selection for the varying coefficient model via local polynomial regression
AU - Kong, Dehan
AU - Bondell, Howard D.
AU - Wu, Yichao
T2 - COMPUTATIONAL STATISTICS & DATA ANALYSIS
AB - In this article, we consider the varying coefficient model, which allows the relationship between the predictors and response to vary across the domain of interest, such as time. In applications, it is possible that certain predictors only affect the response in particular regions and not everywhere. This corresponds to identifying the domain where the varying coefficient is nonzero. Towards this goal, local polynomial smoothing and penalized regression are incorporated into one framework. Asymptotic properties of our penalized estimators are provided. Specifically, the estimators enjoy the oracle properties in the sense that they have the same bias and asymptotic variance as the local polynomial estimators as if the sparsity is known as a priori. The choice of appropriate bandwidth and computational algorithms are discussed. The proposed method is examined via simulations and a real data example.
DA - 2015/3//
PY - 2015/3//
DO - 10.1016/j.csda.2014.10.004
VL - 83
SP - 236-250
SN - 1872-7352
KW - Bandwidth selection
KW - Oracle properties
KW - Penalized local polynomial fitting
KW - SCAD
ER -
TY - JOUR
TI - Diel and life-history characteristics of personality: consistency versus flexibility in relation to ecological change
AU - Watts, J. Colton
AU - Ross, Chelsea R.
AU - Jones, Thomas C.
T2 - ANIMAL BEHAVIOUR
AB - Despite the potential benefits of modifying behaviour according to changing ecological conditions, many populations comprise individuals that differ consistently in behaviour across situations, contexts and points in time (i.e. individuals show personality). If personalities are adaptive, the balance between consistency and flexibility of behavioural traits should reflect the ability of individuals to detect and respond to changing conditions in an appropriate and timely manner and, thus, depend upon the pace and predictability of changing conditions. We investigated the balance between individual consistency and flexibility in the subsocial spider Anelosimus studiosus by assaying boldness across the diel cycle and correlating these data with patterns of prey and threat abundance in the natural habitat. We found significant diel flexibility in boldness correlating with drastic and predictable changes in prey availability. Moreover, the strength of within-individual flexibility in boldness was comparable to the strength of rank-order consistency among individuals. We also found evidence that mean boldness level and among-individual variation in boldness are correlated with reproductive status. These data emphasize the interplay between behavioural consistency and flexibility and suggest that temporal characteristics of ecological conditions may be vital in assessing the strength, stability and adaptive value of animal personalities.
DA - 2015/3//
PY - 2015/3//
DO - 10.1016/j.anbehav.2014.12.020
VL - 101
SP - 43-49
SN - 1095-8282
KW - aggression
KW - Anelosimus studiosus
KW - behavioural flexibility
KW - behavioural types
KW - comb-footed spider
KW - diel rhythm
KW - life history
KW - personality
ER -
TY - JOUR
TI - Complication Rates Associated with Transvenous Pacemaker Implantation in Dogs with High-Grade Atrioventricular Block Performed During versus After Normal Business Hours
AU - Ward, J. L.
AU - DeFrancesco, T. C.
AU - Tou, S. P.
AU - Atkins, C. E.
AU - Griffith, E. H.
AU - Keene, B. W.
T2 - JOURNAL OF VETERINARY INTERNAL MEDICINE
AB - Transvenous pacemaker implantation in dogs is associated with a relatively high complication rate. At our institution, pacemaker implantation in dogs with high-grade atrioventricular block (HG-AVB) frequently is performed as an after-hours emergency.Among dogs with HG-AVB, the rate of major complications is higher when pacemakers are implanted after hours (AH) compared to during business hours (BH).Client-owned dogs with HG-AVB that underwent transvenous pacemaker implantation between January 2002 and December 2012 at the North Carolina State University Veterinary Teaching Hospital.Retrospective medical record review. Two-year follow-up was required for complications analysis.Major complications occurred in 14/79 dogs (18%) and included lead dislodgement, lead or generator infection, lead or generator migration, and pacing failure. Incidence of major complications was significantly higher AH (10/36, 28%) compared to BH (4/43, 9%; P = .041), and all infectious complications occurred AH. Median survival time for all dogs was 27 months and did not differ between AH and BH groups for either all-cause (P = .70) or cardiac (P = .40) mortality. AH dogs were younger than BH dogs (P = .010), but there were no other clinically relevant differences between BH and AH groups in terms of demographic, clinical, or procedural variables.At our institution, AH transvenous pacemaker placement is associated with a higher rate of major complications (especially infections) compared to BH placement. This difference may be because of a variety of human factor differences AH versus BH.
DA - 2015///
PY - 2015///
DO - 10.1111/jvim.12512
VL - 29
IS - 1
SP - 157-163
SN - 1939-1676
KW - Canine
KW - Heart block
KW - Transvenous
ER -
TY - JOUR
TI - On the degrees of freedom in MCMC-based Wishart models for time series data
AU - Xiao, Yuewen
AU - Ku, Yu-Cheng
AU - Bloomfield, Peter
AU - Ghosh, Sujit K.
T2 - STATISTICS & PROBABILITY LETTERS
AB - The Wishart distribution has long been a useful tool for modeling covariance structures. According to Gyndikin’s theorem, the degrees of freedom (df) for a Wishart distribution can be any real number belonging to the Gyndikin set, either integer-valued or fractional. However, the fractional-df versioned Wishart distribution has received only limited attention, which may lead to inaccurate implementation in practice. This paper shows by a numerical example that, when implementing Markov chain Monte Carlo (MCMC) methods in Wishart models for time series data, the lack of attention to the fractional df where necessary can result in seriously biased posterior estimation due to the compounding errors caused by the time dependency assumption. We further conduct a sensitivity analysis to explain why the seemingly small difference between the integer-valued df and the fractional df leads to very different outcomes.
DA - 2015/3//
PY - 2015/3//
DO - 10.1016/j.spl.2014.12.012
VL - 98
SP - 59-64
SN - 1879-2103
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84920930486&partnerID=MN8TOARS
KW - Degrees of freedom
KW - Gyndikin's theorem
KW - Markov chain Monte Carlo
KW - Sensitivity analysis
KW - Wishart distribution
ER -
TY - JOUR
TI - On optimal treatment regimes selection for mean survival time
AU - Geng, Yuan
AU - Zhang, Hao Helen
AU - Lu, Wenbin
T2 - STATISTICS IN MEDICINE
AB - In clinical studies with time‐to‐event as a primary endpoint, one main interest is to find the best treatment strategy to maximize patients' mean survival time. Due to patient's heterogeneity in response to treatments, great efforts have been devoted to developing optimal treatment regimes by integrating individuals' clinical and genetic information. A main challenge arises in the selection of important variables that can help to build reliable and interpretable optimal treatment regimes as the dimension of predictors may be high. In this paper, we propose a robust loss‐based estimation framework that can be easily coupled with shrinkage penalties for both estimation of optimal treatment regimes and variable selection. The asymptotic properties of the proposed estimators are studied. Moreover, a model‐free estimator of restricted mean survival time under the derived optimal treatment regime is developed, and its asymptotic property is studied. Simulations are conducted to assess the empirical performance of the proposed method for parameter estimation, variable selection, and optimal treatment decision. An application to an AIDS clinical trial data set is given to illustrate the method. Copyright © 2014 John Wiley & Sons, Ltd.
DA - 2015/3/30/
PY - 2015/3/30/
DO - 10.1002/sim.6397
VL - 34
IS - 7
SP - 1169-1184
SN - 1097-0258
KW - adaptive LASSO
KW - censored regression
KW - mean survival time
KW - optimal treatment regime
KW - variable selection
ER -
TY - JOUR
TI - Model comparison tests to determine data information content
AU - Banks, H. T.
AU - Banks, J. E.
AU - Link, Kathryn
AU - Rosenheim, J. A.
AU - Ross, Chelsea
AU - Tillman, K. A.
T2 - APPLIED MATHEMATICS LETTERS
AB - In the context of inverse or parameter estimation problems we demonstrate the use of statistically based model comparison tests in several examples of practical interest. In these examples we are interested in questions related to information content of a particular given data set and whether the data will support a more complicated model to describe it. In the first example we compare fits for several different models to describe simple decay in a size histogram for aggregates in amyloid fibril formation. In a second example we investigate whether the information content in data sets for the pest Lygus hesperus in cotton fields as it is currently collected is sufficient to support a model in which one distinguishes between nymphs and adults. Finally in a third example with data for patients having undergone an organ transplant, we question whether the data content is sufficient to estimate more than 5 of the fundamental parameters in a particular dynamic model.
DA - 2015/5//
PY - 2015/5//
DO - 10.1016/j.aml.2014.11.002
VL - 43
SP - 10-18
SN - 0893-9659
KW - Ordinary least squares
KW - Model comparison in inverse problems
KW - Information content
ER -
TY - JOUR
TI - Do Biological and Bedsite Characteristics Influence Survival of Neonatal White-Tailed Deer?
AU - Chitwood, M. Colter
AU - Lashley, Marcus A.
AU - Kilgo, John C.
AU - Pollock, Kenneth H.
AU - Moorman, Christopher E.
AU - DePerno, Christopher S.
T2 - PLOS ONE
AB - Coyotes recently expanded into the eastern U.S. and potentially have caused localized white-tailed deer population declines. Research has focused on quantifying coyote predation on neonates, but little research has addressed the potential influence of bedsite characteristics on survival. In 2011 and 2012, we radiocollared 65 neonates, monitored them intensively for 16 weeks, and assigned mortality causes. We used Program MARK to estimate survival to 16 weeks and included biological covariates (i.e., sex, sibling status [whether or not it had a sibling], birth weight, and Julian date of birth). Survival to 16 weeks was 0.141 (95% CI = 0.075-0.249) and the top model included only sibling status, which indicated survival was lower for neonates that had a sibling. Predation was the leading cause of mortality (35 of 55; 64%) and coyotes were responsible for the majority of depredations (30 of 35; 86%). Additionally, we relocated neonates for the first 10 days of life and measured distance to firebreak, visual obstruction, and plant diversity at bedsites. Survival of predation to 10 days (0.726; 95% CI = 0.586-0.833) was weakly associated with plant diversity at bedsites but not related to visual obstruction. Our results indicate that neonate survival was low and coyote predation was an important source of mortality, which corroborates several recent studies from the region. Additionally, we detected only weak support for bedsite cover as a covariate to neonate survival, which indicates that mitigating effects of coyote predation on neonates may be more complicated than simply managing for increased hiding cover.
DA - 2015/3/3/
PY - 2015/3/3/
DO - 10.1371/journal.pone.0119070
VL - 10
IS - 3
SP -
SN - 1932-6203
ER -
TY - JOUR
TI - Assessing gene-environment interactions for common and rare variants with binary traits using gene-trait similarity regression
AU - Zhao, G. L.
AU - Marceau, R.
AU - Zhang, D. W.
AU - Tzeng, J. Y.
T2 - Genetics
DA - 2015///
PY - 2015///
VL - 199
IS - 3
SP - 695-
ER -
TY - JOUR
TI - An investigation of gene-gene interactions in dose-response studies with Bayesian nonparametrics
AU - Beam, A. L.
AU - Motsinger-Reif, A. A.
AU - Doyle, J.
T2 - Biodata Mining
DA - 2015///
PY - 2015///
VL - 8
ER -
TY - JOUR
TI - Investigating the filled gel model in Cheddar cheese through use of Sephadex beads
AU - Barden, L. M.
AU - Osborne, J. A.
AU - McMahon, D. J.
AU - Foegeding, E. A.
T2 - JOURNAL OF DAIRY SCIENCE
AB - Cheese can be modeled as a filled gel whereby milkfat globules are dispersed in a casein gel network. We determined the filler effects using Sephadex beads (GE Healthcare Life Sciences, Pittsburgh, PA) as a model filler particle. Ideally, such a model could be used to test novel filler particles to replace milkfat in low-fat cheese. Low-filler (6% particles), reduced-filler (16%), and full-filler (33%) cheeses were produced using either Sephadex beads of varying sizes (20 to 150 μm diameter) or milkfat. Small- and large-strain rheological tests were run on each treatment at 8, 12, and 18 wk after cheese manufacturing. Differences in rheological properties were caused primarily by the main effects of filler volume and type (milkfat vs. Sephadex), whereas filler size had no obvious effect. All treatments showed a decrease in deformability and an increase in firmness as filler volume increased above 25%, although the beads exhibited a greater reinforcing effect and greater energy recovery than milkfat.
DA - 2015/3//
PY - 2015/3//
DO - 10.3168/jds.2014-8597
VL - 98
IS - 3
SP - 1502-1516
SN - 1525-3198
KW - cheese
KW - filled gel
KW - Sephadex
KW - particle size
ER -
TY - JOUR
TI - Initial evaluation of nighttime restlessness in a naturally occurring canine model of osteoarthritis pain
AU - Knazovicky, D.
AU - Tomas, A.
AU - Motsinger-Reif, A.
AU - Lascelles, B. D. X.
T2 - PeerJ
DA - 2015///
PY - 2015///
VL - 3
ER -
TY - JOUR
TI - Global Analysis of Methylation Profiles From High Resolution CpG Data
AU - Zhao, Ni
AU - Bell, Douglas A.
AU - Maity, Arnab
AU - Staicu, Ana-Maria
AU - Joubert, Bonnie R.
AU - London, Stephanie J.
AU - Wu, Michael C.
T2 - GENETIC EPIDEMIOLOGY
AB - ABSTRACT New high throughput technologies are now enabling simultaneous epigenetic profiling of DNA methylation at hundreds of thousands of CpGs across the genome. A problem of considerable practical interest is identification of large scale, global changes in methylation that are associated with environmental variables, clinical outcomes, or other experimental conditions. However, there has been little statistical research on methods for global methylation analysis using technologies with individual CpG resolution. To address this critical gap in the literature, we develop a new strategy for global analysis of methylation profiles using a functional regression approach wherein we approximate either the density or the cumulative distribution function (CDF) of the methylation values for each individual using B‐spline basis functions. The spline coefficients for each individual are allowed to summarize the individual's overall methylation profile. We then test for association between the overall distribution and a continuous or dichotomous outcome variable using a variance component score test that naturally accommodates the correlation between spline coefficients. Simulations indicate that our proposed approach has desirable power while protecting type I error. The method was applied to detect methylation differences, both genome wide and at LINE1 elements, between the blood samples from rheumatoid arthritis patients and healthy controls and to detect the epigenetic changes of human hepatocarcinogenesis in the context of alcohol abuse and hepatitis C virus infection. A free implementation of our methods in the R language is available in the Global Analysis of Methylation Profiles (GAMP) package at http://research.fhcrc.org/wu/en.html .
DA - 2015/2//
PY - 2015/2//
DO - 10.1002/gepi.21874
VL - 39
IS - 2
SP - 53-64
SN - 1098-2272
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84921023434&partnerID=MN8TOARS
KW - density approximation
KW - epigenome wide association study
KW - global testing
KW - spline smoothing
KW - variance component testing
ER -
TY - JOUR
TI - GLP-1 plays a limited role in improved glycemia shortly after Roux-en-Y gastric bypass: A comparison with intensive lifestyle modification
AU - Vetter, M. L.
AU - Wadden, T. A.
AU - Teff, K. L.
AU - Khan, Z. F.
AU - Carvajal, R.
AU - Ritter, S.
AU - Moore, R. H.
AU - Chittams, J. L.
AU - Iagnocco, A.
AU - Murayama, K.
AU - Korus, G.
AU - Williams, N. N.
AU - Rickels, M. R.
T2 - Diabetes
AB - Rapid glycemic improvements following Roux-en-Y gastric bypass (RYGB) are frequently attributed to the enhanced GLP-1 response, but causality remains unclear. To determine the role of GLP-1 in improved glucose tolerance after surgery, we compared glucose and hormonal responses to a liquid meal test in 20 obese participants with type 2 diabetes mellitus who underwent RYGB or nonsurgical intensive lifestyle modification (ILM) (n = 10 per group) before and after equivalent short-term weight reduction. The GLP-1 receptor antagonist exendin(9–39)-amide (Ex-9) was administered, in random order and in double-blinded fashion, with saline during two separate visits after equivalent weight loss. Despite the markedly exaggerated GLP-1 response after RYGB, changes in postprandial glucose and insulin responses did not significantly differ between groups, and glucagon secretion was paradoxically augmented after RYGB. Hepatic insulin sensitivity also increased significantly after RYGB. With Ex-9, glucose tolerance deteriorated similarly from the saline condition in both groups, but postprandial insulin release was markedly attenuated after RYGB compared with ILM. GLP-1 exerts important insulinotropic effects after RYGB and ILM, but the enhanced incretin response plays a limited role in improved glycemia shortly after surgery. Instead, enhanced hepatic metabolism, independent of GLP-1 receptor activation, may be more important for early postsurgical glycemic improvements.
DA - 2015///
PY - 2015///
DO - 10.2337/db14-0558
VL - 64
IS - 2
SP - 434-446
ER -
TY - JOUR
TI - False discovery control in large-scale spatial multiple testing
AU - Sun, Wenguang
AU - Reich, Brian J.
AU - Cai, T. Tony
AU - Guindani, Michele
AU - Schwartzman, Armin
T2 - JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY
AB - This article develops a unified theoretical and computational framework for false discovery control in multiple testing of spatial signals. We consider both point-wise and cluster-wise spatial analyses, and derive oracle procedures which optimally control the false discovery rate, false discovery exceedance and false cluster rate, respectively. A data-driven finite approximation strategy is developed to mimic the oracle procedures on a continuous spatial domain. Our multiple testing procedures are asymptotically valid and can be effectively implemented using Bayesian computational algorithms for analysis of large spatial data sets. Numerical results show that the proposed procedures lead to more accurate error control and better power performance than conventional methods. We demonstrate our methods for analyzing the time trends in tropospheric ozone in eastern US.
DA - 2015/1//
PY - 2015/1//
DO - 10.1111/rssb.12064
VL - 77
IS - 1
SP - 59-83
SN - 1467-9868
KW - Compound decision theory
KW - False cluster rate
KW - False discovery exceedance
KW - False discovery rate
KW - Large-scale multiple testing
KW - Spatial dependence
ER -
TY - JOUR
TI - Estimation of time-varying mortality rates using continuous models for Daphnia magna
AU - Adoteye, Kaska
AU - Banks, H. T.
AU - Flores, Kevin B.
AU - LeBlanc, Gerald A.
T2 - APPLIED MATHEMATICS LETTERS
AB - Structured population models that make the assumption of constant demographic rates do not accurately describe the complex life histories seen in many species. We investigated the accuracy of using constant versus time-varying mortality rates within discrete and continuously structured models for Daphnia magna. We tested the accuracy of the models we considered using density-independent survival data for 90 daphnids. We found that a continuous differential equation model with a time-varying mortality rate was the most accurate model for describing our experimental D. magna survival data. Our results suggest that differential equation models with variable parameters are an accurate tool for estimating mortality rates in biological scenarios in which mortality might vary significantly with age.
DA - 2015/6//
PY - 2015/6//
DO - 10.1016/j.aml.2014.12.014
VL - 44
SP - 12-16
SN - 1873-5452
KW - Structured population model
KW - Leslie matrix model
KW - Sinko-Streifer model
KW - Daphnia magna
KW - Time-dependent mortality rate
ER -
TY - JOUR
TI - Estimating Spatially Varying Severity Thresholds of a Forest Fire Danger Rating System Using Max-Stable Extreme-Event Modeling
AU - Stephenson, Alec G.
AU - Shaby, Benjamin A.
AU - Reich, Brian J.
AU - Sullivan, Andrew L.
T2 - JOURNAL OF APPLIED METEOROLOGY AND CLIMATOLOGY
AB - Abstract Fire danger indices are used in many countries to estimate the potential fire danger and to issue warnings to local regions. The McArthur fire danger rating system is used in Australia. The McArthur forest fire danger index (FFDI) uses only meteorological elements. It combines information on wind speed, temperature, relative humidity, and recent rainfall to produce a weather index of fire potential. This index is converted into fire danger categories to serve as warnings to the local population and to estimate potential fire-suppression difficulty. FFDI values above the threshold of 75 are rated as extreme. The spatial behavior of large values of the FFDI is modeled to investigate whether a varying threshold across space may serve as a better guide for determining the onset of elevated fire danger. The authors modify and apply a statistical method that was recently developed for spatial extreme events, using a “max-stable” process to model FFDI data at approximately 17 000 data sites. The method that is described here produces a quantile map that can be employed as a spatially varying fire danger threshold. It is found that a spatially varying threshold may serve to more accurately represent high fire danger, and an adjustment is proposed that varies by local government area. Temporal change was also investigated, and evidence was found of a recent increase in extreme fire danger in southwestern Australia.
DA - 2015/2//
PY - 2015/2//
DO - 10.1175/jamc-d-14-0041.1
VL - 54
IS - 2
SP - 395-407
SN - 1558-8432
ER -
TY - JOUR
TI - Complete Effect-Profile Assessment in Association Studies With Multiple Genetic and Multiple Environmental Factors
AU - Wang, Zhi
AU - Maity, Arnab
AU - Luo, Yiwen
AU - Neely, Megan L.
AU - Tzeng, Jung-Ying
T2 - GENETIC EPIDEMIOLOGY
AB - ABSTRACT Studying complex diseases in the post genome‐wide association studies (GWAS) era has led to developing methods that consider factor‐sets rather than individual genetic/environmental factors (i.e., Multi‐G‐Multi‐E studies), and mining for potential gene‐environment (G×E) interactions has proven to be an invaluable aid in both discovery and deciphering underlying biological mechanisms. Current approaches for examining effect profiles in Multi‐G‐Multi‐E analyses are either underpowered due to large degrees of freedom, ill‐suited for detecting G×E interactions due to imprecise modeling of the G and E effects, or lack of capacity for modeling interactions between two factor‐sets (e.g., existing methods focus primarily on a single E factor). In this work, we illustrate the issues encountered in constructing kernels for investigating interactions between two factor‐sets, and propose a simple yet intuitive solution to construct the G×E kernel that retains the ease‐of‐interpretation of classic regression. We also construct a series of kernel machine (KM) score tests to evaluate the complete effect profile (i.e., the G, E, and G×E effects individually or in combination). We show, via simulations and a data application, that the proposed KM methods outperform the classic and PC regressions across a range of scenarios, including varying effect size, effect structure, and interaction complexity. The largest power gain was observed when the underlying effect structure involved complex G×E interactions; however, the proposed methods have consistent, powerful performance when the effect profile is simple or complex, suggesting that the proposed method could be a useful tool for exploratory or confirmatory G×E analysis.
DA - 2015/2//
PY - 2015/2//
DO - 10.1002/gepi.21877
VL - 39
IS - 2
SP - 122-133
SN - 1098-2272
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84921048438&partnerID=MN8TOARS
KW - factor-set association analysis
KW - kernel machine regression
KW - genetic-environmental interactions
KW - joint and conditional tests
ER -
TY - JOUR
TI - Optimal design of non-equilibrium experiments for genetic network interrogation
AU - Adoteye, Kaska
AU - Banks, H. T.
AU - Flores, Kevin B.
T2 - APPLIED MATHEMATICS LETTERS
AB - Many experimental systems in biology, especially synthetic gene networks, are amenable to perturbations that are controlled by the experimenter. We developed an optimal design algorithm that calculates optimal observation times in conjunction with optimal experimental perturbations in order to maximize the amount of information gained from longitudinal data derived from such experiments. We applied the algorithm to a validated model of a synthetic Brome Mosaic Virus (BMV) gene network and found that optimizing experimental perturbations may substantially decrease uncertainty in estimating BMV model parameters.
DA - 2015/2//
PY - 2015/2//
DO - 10.1016/j.aml.2014.09.013
VL - 40
SP - 84-89
SN - 0893-9659
KW - Optimal experimental design
KW - Inverse problem
KW - Uncertainty analysis
KW - Brome mosaic virus
KW - Synthetic biology
KW - Genetic networks
ER -
TY - JOUR
TI - Significance tests for functional data with complex dependence structure
AU - Staicu, Ana-Maria
AU - Lahiri, Soumen N.
AU - Carroll, Raymond J.
T2 - JOURNAL OF STATISTICAL PLANNING AND INFERENCE
AB - We propose an L2-norm based global testing procedure for the null hypothesis that multiple group mean functions are equal, for functional data with complex dependence structure. Specifically, we consider the setting of functional data with a multilevel structure of the form groups-clusters or subjects-units, where the unit-level profiles are spatially correlated within the cluster, and the cluster-level data are independent. Orthogonal series expansions are used to approximate the group mean functions and the test statistic is estimated using the basis coefficients. The asymptotic null distribution of the test statistic is developed, under mild regularity conditions. To our knowledge this is the first work that studies hypothesis testing, when data have such complex multilevel functional and spatial structure. Two small-sample alternatives, including a novel block bootstrap for functional data, are proposed, and their performance is examined in simulation studies. The paper concludes with an illustration of a motivating experiment.
DA - 2015/1//
PY - 2015/1//
DO - 10.1016/j.jspi.2014.08.006
VL - 156
SP - 1-13
SN - 1873-1171
KW - Block bootstrap
KW - Functional data
KW - Group mean testing
KW - Hierarchical modeling
KW - Significance tests
KW - Spatially correlated curves
ER -
TY - JOUR
TI - Nonparametric Regression for Estimation of Spatiotemporal Mountain Glacier Retreat From Satellite Images
AU - Kachouie, Nezamoddin N.
AU - Gerke, Travis
AU - Huybers, Peter
AU - Schwartzman, Armin
T2 - IEEE TRANSACTIONS ON GEOSCIENCE AND REMOTE SENSING
AB - Historical variations in the extent of mountain glaciers give insight into natural and forced changes of these bellwethers of the climate. Because of the limited number of ground observations relative to the number of glaciers, it is useful to develop techniques that permit for the monitoring of glacier systems using satellite imagery. Here, we propose a new approach for identifying the glacier terminus over time from Landsat images. The proposed method permits for detecting inflection points in multispectral satellite imagery taken along a glacier's flow path in order to identify candidate terminus locations. A gated tracking algorithm is then applied to identify the best candidate for the glacier terminus location through time. Finally, the long-term trend of the terminus position is estimated with uncertainty bounds. This is achieved by applying nonparametric regression to the temporal sequence of estimated terminus locations. The method is shown to give results consistent with ground-based observations for the Franz Josef and Gorner glaciers and is further applied to estimate the retreat of Viedma, a glacier with no available ground measurements.
DA - 2015/3//
PY - 2015/3//
DO - 10.1109/tgrs.2014.2334643
VL - 53
IS - 3
SP - 1135-1149
SN - 1558-0644
KW - Curve fitting
KW - glacier terminus
KW - global warming
KW - local polynomial regression
KW - plug-in bandwidth selection
KW - spatiotemporal analysis
KW - tracking
ER -