@article {bai2016activity, title = {An activity index for raw accelerometry data and its comparison with other activity metrics}, journal = {PloS ONE}, volume = {11}, number = {8}, year = {2016}, pages = {e0160644}, publisher = {Public Library of Science}, author = {Bai, Jiawei and Di, Chongzhi and Xiao, Luo and Evenson, Kelly R and LaCroix, Andrea Z and Crainiceanu, Ciprian M and Buchner, David M} } @article {819, title = {Analytic programming with FMRI data: a quick-start guide for statisticians using R.}, journal = {PLoS One}, volume = {9}, year = {2014}, month = {2014}, pages = {e89470}, abstract = {

Functional magnetic resonance imaging (fMRI) is a thriving field that plays an important role in medical imaging analysis, biological and neuroscience research and practice. This manuscript gives a didactic introduction to the statistical analysis of fMRI data using the R project, along with the relevant R code. The goal is to give statisticians who would like to pursue research in this area a quick tutorial for programming with fMRI data. References of relevant packages and papers are provided for those interested in more advanced analysis.

}, keywords = {Brain, brain mapping, Humans, Magnetic Resonance Imaging, Programming Languages}, issn = {1932-6203}, doi = {10.1371/journal.pone.0089470}, author = {Eloyan, Ani and Li, Shanshan and Muschelli, John and Pekar, Jim J and Mostofsky, Stewart H and Caffo, Brian S} } @article {798, title = {Assessing the "physical cliff": detailed quantification of age-related differences in daily patterns of physical activity.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {69}, year = {2014}, month = {2014 Aug}, pages = {973-9}, abstract = {

BACKGROUND: In spite of evidence that physical activity has beneficial effects on health and age-related functional decline, there is a scarcity of detailed and accurate information on objectively measured daily activity and patterns of such activity in older adults.

METHODS: Participants in the Baltimore Longitudinal Study of Aging (n = 611, 50\% male, mean age 67, range 32-93) wore the Actiheart portable activity monitor for 7 days in the free-living environment. The association between activity and age was modeled using a continuous log-linear regression of activity counts on age with sex, body mass index, employment status, functional performance, and comorbid conditions as covariates.

RESULTS: In the fully adjusted model, continuous analyses demonstrated that overall physical activity counts were 1.3\% lower for each year increase in age. Although there were no differences among morning levels of activity, there was significantly lower afternoon and evening activity in older individuals (p < .01). After adjusting for age, poor functional performance, nonworking status, and higher body mass index were independently associated with less physical activity (p < .001).

CONCLUSIONS: The use of accelerometers to characterize minute-by-minute intensity, cumulative physical activity counts, and daily activity patterns provides detailed data not gathered by traditional subjective methods, particularly at low levels of activity. The findings of a 1.3\% decrease per year in activity from mid-to-late life, and the corresponding drop in afternoon and evening activity, provide new information that may be useful when targeting future interventions. Further, this methodology addresses essential gaps in understanding activity patterns and trends in more sedentary sectors of the population.

}, keywords = {Accelerometry, Adult, Age Factors, Aged, Aged, 80 and over, Employment, Female, Health Behavior, Humans, Linear Models, Longitudinal Studies, Male, Middle Aged, Motor Activity, Physical Fitness, Sedentary Lifestyle}, issn = {1758-535X}, doi = {10.1093/gerona/glt199}, author = {Schrack, Jennifer A and Zipunnikov, Vadim and Goldsmith, Jeff and Bai, Jiawei and Simonsick, Eleanor M and Crainiceanu, Ciprian and Ferrucci, Luigi} } @article {797, title = {Biomarkers of vascular calcification and mortality in patients with ESRD.}, journal = {Clin J Am Soc Nephrol}, volume = {9}, year = {2014}, month = {2014 Apr}, pages = {745-55}, abstract = {

BACKGROUND: Vascular calcification is common among patients undergoing dialysis and is associated with mortality. Factors such as osteoprotegerin (OPG), osteopontin (OPN), bone morphogenic protein-7 (BMP-7), and fetuin-A are involved in vascular calcification.

DESIGN, SETTING, PARTICIPANTS, \& MEASUREMENTS: OPG, OPN, BMP-7, and fetuin-A were measured in blood samples from 602 incident dialysis patients recruited from United States dialysis centers between 1995 and 1998 as part of the Choices for Healthy Outcomes In Caring for ESRD Study. Their association with all-cause and cardiovascular mortality were assessed using Cox proportional hazards models adjusted for demographic characteristics, comorbidity, serum phosphate, and calcium. An interaction with diabetes was tested because of its known association with vascular calcification. Predictive accuracy of selected biomarkers was explored by C-statistics in nested models with training and validation subcohorts.

RESULTS: Higher OPG and lower fetuin-A levels were associated with higher mortality over up to 13 years of follow-up (median, 3.4 years). The adjusted hazard ratios (HR) for highest versus lowest tertile were 1.49 (95\% confidence interval [95\% CI], 1.08 to 2.06) for OPG and 0.69 (95\% CI, 0.52 to 0.92) for fetuin-A. In stratified models, the highest tertile of OPG was associated with higher mortality among patients without diabetes (HR, 2.42; 95\% CI, 1.35 to 4.34), but not patients with diabetes (HR, 1.26; 95\% CI, 0.82 to 1.93; P for interaction=0.001). In terms of cardiovascular mortality, higher fetuin-A was associated with lower risk (HR, 0.85 per 0.1 g/L: 95\% CI, 0.75 to 0.96). In patients without diabetes, higher OPG was associated with greater risk (HR for highest versus lowest tertile, 2.91; 95\% CI, 1.06 to 7.99), but not in patients with diabetes or overall. OPN and BMP-7 were not independently associated with outcomes overall. The addition of OPG and fetuin-A did not significantly improve predictive accuracy of mortality.

CONCLUSIONS: OPG and fetuin-A may be risk factors for all-cause and cardiovascular mortality in patients undergoing dialysis, but do not improve risk prediction.

}, issn = {1555-905X}, doi = {10.2215/CJN.05450513}, author = {Scialla, Julia J and Kao, W H Linda and Crainiceanu, Ciprian and Sozio, Stephen M and Oberai, Pooja C and Shafi, Tariq and Coresh, Josef and Powe, Neil R and Plantinga, Laura C and Jaar, Bernard G and Parekh, Rulan S} } @article {795, title = {A comparison of supervised machine learning algorithms and feature vectors for MS lesion segmentation using multimodal structural MRI.}, journal = {PLoS One}, volume = {9}, year = {2014}, month = {2014}, pages = {e95753}, abstract = {

Machine learning is a popular method for mining and analyzing large collections of medical data. We focus on a particular problem from medical research, supervised multiple sclerosis (MS) lesion segmentation in structural magnetic resonance imaging (MRI). We examine the extent to which the choice of machine learning or classification algorithm and feature extraction function impacts the performance of lesion segmentation methods. As quantitative measures derived from structural MRI are important clinical tools for research into the pathophysiology and natural history of MS, the development of automated lesion segmentation methods is an active research field. Yet, little is known about what drives performance of these methods. We evaluate the performance of automated MS lesion segmentation methods, which consist of a supervised classification algorithm composed with a feature extraction function. These feature extraction functions act on the observed T1-weighted (T1-w), T2-weighted (T2-w) and fluid-attenuated inversion recovery (FLAIR) MRI voxel intensities. Each MRI study has a manual lesion segmentation that we use to train and validate the supervised classification algorithms. Our main finding is that the differences in predictive performance are due more to differences in the feature vectors, rather than the machine learning or classification algorithms. Features that incorporate information from neighboring voxels in the brain were found to increase performance substantially. For lesion segmentation, we conclude that it is better to use simple, interpretable, and fast algorithms, such as logistic regression, linear discriminant analysis, and quadratic discriminant analysis, and to develop the features to improve performance.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0095753}, author = {Sweeney, Elizabeth M and Vogelstein, Joshua T and Cuzzocreo, Jennifer L and Calabresi, Peter A and Reich, Daniel S and Crainiceanu, Ciprian M and Shinohara, Russell T} } @article {833, title = {Cross-sectional and longitudinal association of body mass index and brain volume.}, journal = {Hum Brain Mapp}, volume = {35}, year = {2014}, month = {2014 Jan}, pages = {75-88}, abstract = {

Although a link between body mass index (BMI) and brain volume has been established in several cross-sectional studies, evidence of the association between change in BMI over time and changes in brain structure is limited. Using data from a cohort of 347 former lead workers and community controls with two magnetic resonance imaging scans over a period of ~5 years, we estimated cross-sectional and longitudinal associations of BMI and brain volume using both region of interest (ROI) and voxel-based morphometric (VBM) methods. We found that associations of BMI and brain volume were not significantly different in former lead workers when compared with community controls. In the cross-sectional analysis, higher BMIs were associated with smaller brain volumes in gray matter (GM) using both ROI and VBM approaches. No associations with white matter (WM) were observed. In the longitudinal analysis, higher baseline BMI was associated with greater decline in temporal and occipital GM ROI volumes. Change in BMI over the 5-year period was only associated with change in hippocampal volume and was not associated with change in any of the GM ROIs. Overall, higher BMI was associated with lower GM volume in several ROIs and with declines in volume in temporal and occipital GM over time. These results suggest that sustained high body mass may contribute to progressive temporal and occipital atrophy.

}, keywords = {Aged, Atrophy, Body Mass Index, Brain, Cross-Sectional Studies, Humans, Image Interpretation, Computer-Assisted, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Obesity}, issn = {1097-0193}, doi = {10.1002/hbm.22159}, author = {Bobb, Jennifer F and Schwartz, Brian S and Davatzikos, Christos and Caffo, Brian} } @article {831, title = {Disruption of functional organization within the primary motor cortex in children with autism.}, journal = {Hum Brain Mapp}, volume = {35}, year = {2014}, month = {2014 Feb}, pages = {567-80}, abstract = {

Accumulating evidence suggests that motor impairments are prevalent in autism spectrum disorder (ASD), relate to the social and communicative deficits at the core of the diagnosis and may reflect abnormal connectivity within brain networks underlying motor control and learning. Parcellation of resting-state functional connectivity data using spectral clustering approaches has been shown to be an effective means of visualizing functional organization within the brain but has most commonly been applied to explorations of normal brain function. This article presents a parcellation of a key area of the motor network, the primary motor cortex (M1), a key area of the motor control network, in adults, typically developing (TD) children and children with ASD and introduces methods for selecting the number of parcels, matching parcels across groups and testing group differences. The parcellation is based solely on patterns of connectivity between individual M1 voxels and all voxels outside of M1, and within all groups, a gross dorsomedial to ventrolateral organization emerged within M1 which was left-right symmetric. Although this gross organizational scheme was present in both groups of children, statistically significant group differences in the size and segregation of M1 parcels within regions of the motor homunculus corresponding to the upper and lower limbs were observed. Qualitative comparison of the M1 parcellation for children with ASD with that of younger and older TD children suggests that these organizational differences, with a lack of differentiation between lower limb/trunk regions and upper limb/hand regions, may be due, at least in part, to a delay in functional specialization within the motor cortex.

}, keywords = {Adult, Autistic Disorder, brain mapping, Child, Developmental Disabilities, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Motor Cortex, Oxygen, Young Adult}, issn = {1097-0193}, doi = {10.1002/hbm.22188}, author = {Nebel, Mary Beth and Joel, Suresh E and Muschelli, John and Barber, Anita D and Caffo, Brian S and Pekar, James J and Mostofsky, Stewart H} } @article {794, title = {Estimating energy expenditure from heart rate in older adults: a case for calibration.}, journal = {PLoS One}, volume = {9}, year = {2014}, month = {2014}, pages = {e93520}, abstract = {

BACKGROUND: Accurate measurement of free-living energy expenditure is vital to understanding changes in energy metabolism with aging. The efficacy of heart rate as a surrogate for energy expenditure is rooted in the assumption of a linear function between heart rate and energy expenditure, but its validity and reliability in older adults remains unclear.

OBJECTIVE: To assess the validity and reliability of the linear function between heart rate and energy expenditure in older adults using different levels of calibration.

DESIGN: Heart rate and energy expenditure were assessed across five levels of exertion in 290 adults participating in the Baltimore Longitudinal Study of Aging. Correlation and random effects regression analyses assessed the linearity of the relationship between heart rate and energy expenditure and cross-validation models assessed predictive performance.

RESULTS: Heart rate and energy expenditure were highly correlated (r=0.98) and linear regardless of age or sex. Intra-person variability was low but inter-person variability was high, with substantial heterogeneity of the random intercept (s.d. =0.372) despite similar slopes. Cross-validation models indicated individual calibration data substantially improves accuracy predictions of energy expenditure from heart rate, reducing the potential for considerable measurement bias. Although using five calibration measures provided the greatest reduction in the standard deviation of prediction errors (1.08 kcals/min), substantial improvement was also noted with two (0.75 kcals/min).

CONCLUSION: These findings indicate standard regression equations may be used to make population-level inferences when estimating energy expenditure from heart rate in older adults but caution should be exercised when making inferences at the individual level without proper calibration.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0093520}, author = {Schrack, Jennifer A and Zipunnikov, Vadim and Goldsmith, Jeff and Bandeen-Roche, Karen and Crainiceanu, Ciprian M and Ferrucci, Luigi} } @article {835, title = {Evaluating dynamic bivariate correlations in resting-state fMRI: a comparison study and a new approach.}, journal = {Neuroimage}, volume = {101}, year = {2014}, month = {2014 Nov 1}, pages = {531-46}, abstract = {

To date, most functional Magnetic Resonance Imaging (fMRI) studies have assumed that the functional connectivity (FC) between time series from distinct brain regions is constant across time. However, recently, there has been an increased interest in quantifying possible dynamic changes in FC during fMRI experiments, as it is thought that this may provide insight into the fundamental workings of brain networks. In this work we focus on the specific problem of estimating the dynamic behavior of pair-wise correlations between time courses extracted from two different regions of the brain. We critique the commonly used sliding-window technique, and discuss some alternative methods used to model volatility in the finance literature that could also prove to be useful in the neuroimaging setting. In particular, we focus on the Dynamic Conditional Correlation (DCC) model, which provides a model-based approach towards estimating dynamic correlations. We investigate the properties of several techniques in a series of simulation studies and find that DCC achieves the best overall balance between sensitivity and specificity in detecting dynamic changes in correlations. We also investigate its scalability beyond the bivariate case to demonstrate its utility for studying dynamic correlations between more than two brain regions. Finally, we illustrate its performance in an application to test-retest resting state fMRI data.

}, issn = {1095-9572}, doi = {10.1016/j.neuroimage.2014.06.052}, author = {Lindquist, Martin A and Xu, Yuting and Nebel, Mary Beth and Caffo, Brain S} } @article {822, title = {An evaluation of independent component analyses with an application to resting-state fMRI.}, journal = {Biometrics}, volume = {70}, year = {2014}, month = {2014 Mar}, pages = {224-36}, abstract = {

We examine differences between independent component analyses (ICAs) arising from different assumptions, measures of dependence, and starting points of the algorithms. ICA is a popular method with diverse applications including artifact removal in electrophysiology data, feature extraction in microarray data, and identifying brain networks in functional magnetic resonance imaging (fMRI). ICA can be viewed as a generalization of principal component analysis (PCA) that takes into account higher-order cross-correlations. Whereas the PCA solution is unique, there are many ICA methods-whose solutions may differ. Infomax, FastICA, and JADE are commonly applied to fMRI studies, with FastICA being arguably the most popular. Hastie and Tibshirani (2003) demonstrated that ProDenICA outperformed FastICA in simulations with two components. We introduce the application of ProDenICA to simulations with more components and to fMRI data. ProDenICA was more accurate in simulations, and we identified differences between biologically meaningful ICs from ProDenICA versus other methods in the fMRI analysis. ICA methods require nonconvex optimization, yet current practices do not recognize the importance of, nor adequately address sensitivity to, initial values. We found that local optima led to dramatically different estimates in both simulations and group ICA of fMRI, and we provide evidence that the global optimum from ProDenICA is the best estimate. We applied a modification of the Hungarian (Kuhn-Munkres) algorithm to match ICs from multiple estimates, thereby gaining novel insights into how brain networks vary in their sensitivity to initial values and ICA method.

}, keywords = {Adolescent, Algorithms, Attention Deficit Disorder with Hyperactivity, brain mapping, Child, Child, Preschool, Computer Simulation, Humans, Magnetic Resonance Imaging, Models, Statistical, Principal Component Analysis}, issn = {1541-0420}, doi = {10.1111/biom.12111}, author = {Risk, Benjamin B and Matteson, David S and Ruppert, David and Eloyan, Ani and Caffo, Brian S} } @article {816, title = {Evidence for Specificity of Motor Impairments in Catching and Balance in Children with Autism.}, journal = {J Autism Dev Disord}, year = {2014}, month = {2014 Sep 18}, abstract = {

To evaluate evidence for motor impairment specificity in autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). Children completed performance-based assessment of motor functioning (Movement Assessment Battery for Children: MABC-2). Logistic regression models were used to predict group membership. In the models comparing typically developing and developmental disability (DD), all three MABC subscale scores were significantly negatively associated with having a DD. In the models comparing ADHD and ASD, catching and static balance items were associated with ASD group membership, with a 1 point decrease in performance increasing odds of ASD by 36 and 39~\%, respectively. Impairments in motor skills requiring the coupling of visual and temporal feedback to guide and adjust movement appear specifically deficient in ASD.

}, issn = {1573-3432}, doi = {10.1007/s10803-014-2229-0}, author = {Ament, Katarina and Mejia, Amanda and Buhlman, Rebecca and Erklin, Shannon and Caffo, Brian and Mostofsky, Stewart and Wodka, Ericka} } @article {790, title = {Health effects of lesion localization in multiple sclerosis: spatial registration and confounding adjustment.}, journal = {PLoS One}, volume = {9}, year = {2014}, month = {2014}, pages = {e107263}, abstract = {

Brain lesion localization in multiple sclerosis (MS) is thought to be associated with the type and severity of adverse health effects. However, several factors hinder statistical analyses of such associations using large MRI datasets: 1) spatial registration algorithms developed for healthy individuals may be less effective on diseased brains and lead to different spatial distributions of lesions; 2) interpretation of results requires the careful selection of confounders; and 3) most approaches have focused on voxel-wise regression approaches. In this paper, we evaluated the performance of five registration algorithms and observed that conclusions regarding lesion localization can vary substantially with the choice of registration algorithm. Methods for dealing with confounding factors due to differences in disease duration and local lesion volume are introduced. Voxel-wise regression is then extended by the introduction of a metric that measures the distance between a patient-specific lesion mask and the population prevalence map.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0107263}, author = {Eloyan, Ani and Shou, Haochang and Shinohara, Russell T and Sweeney, Elizabeth M and Nebel, Mary Beth and Cuzzocreo, Jennifer L and Calabresi, Peter A and Reich, Daniel S and Lindquist, Martin A and Crainiceanu, Ciprian M} } @article {793, title = {Multilevel sparse functional principal component analysis.}, journal = {Stat}, volume = {3}, year = {2014}, month = {2014 Jan 29}, pages = {126-143}, abstract = {

We consider analysis of sparsely sampled multilevel functional data, where the basic observational unit is a function and data have a natural hierarchy of basic units. An example is when functions are recorded at multiple visits for each subject. Multilevel functional principal component analysis (MFPCA; Di et al. 2009) was proposed for such data when functions are densely recorded. Here we consider the case when functions are sparsely sampled and may contain only a few observations per function. We exploit the multilevel structure of covariance operators and achieve data reduction by principal component decompositions at both between and within subject levels. We address inherent methodological differences in the sparse sampling context to: 1) estimate the covariance operators; 2) estimate the functional principal component scores; 3) predict the underlying curves. Through simulations the proposed method is able to discover dominating modes of variations and reconstruct underlying curves well even in sparse settings. Our approach is illustrated by two applications, the Sleep Heart Health Study and eBay auctions.

}, issn = {0038-9986}, doi = {10.1002/sta4.50}, author = {Di, Chongzhi and Crainiceanu, Ciprian M and Jank, Wolfgang S} } @article {817, title = {The neural correlates of learned motor acuity.}, journal = {J Neurophysiol}, volume = {112}, year = {2014}, month = {2014 Aug 15}, pages = {971-80}, abstract = {

We recently defined a component of motor skill learning as "motor acuity," quantified as a shift in the speed-accuracy trade-off function for a task. These shifts are primarily driven by reductions in movement variability. To determine the neural correlates of improvement in motor acuity, we devised a motor task compatible with magnetic resonance brain imaging that required subjects to make finely controlled wrist movements under visual guidance. Subjects were imaged on day 1 and day 5 while they performed this task and were trained outside the scanner on intervening days 2, 3, and 4. The potential confound of performance changes between days 1 and 5 was avoided by constraining movement time to a fixed duration. After training, subjects showed a marked increase in success rate and a reduction in trial-by-trial variability for the trained task but not for an untrained control task, without changes in mean trajectory. The decrease in variability for the trained task was associated with increased activation in contralateral primary motor and premotor cortical areas and in ipsilateral cerebellum. A global nonlocalizing multivariate analysis confirmed that learning was associated with increased overall brain activation. We suggest that motor acuity is acquired through increases in the number of neurons recruited in contralateral motor cortical areas and in ipsilateral cerebellum, which could reflect increased signal-to-noise ratio in motor output and improved state estimation for feedback corrections, respectively.

}, issn = {1522-1598}, doi = {10.1152/jn.00897.2013}, author = {Shmuelof, Lior and Yang, Juemin and Caffo, Brian and Mazzoni, Pietro and Krakauer, John W} } @article {815, title = {Neuroinflammation and brain atrophy in former NFL players: An in vivo multimodal imaging pilot study.}, journal = {Neurobiol Dis}, volume = {74C}, year = {2014}, month = {2014 Nov 7}, pages = {58-65}, abstract = {

There are growing concerns about potential delayed, neuropsychiatric consequences (e.g, cognitive decline, mood or anxiety disorders) of sports-related traumatic brain injury (TBI). Autopsy studies of brains from a limited number of former athletes have described characteristic, pathologic changes of chronic traumatic encephalopathy (CTE) leading to questions about the relationship between these pathologic and the neuropsychiatric disturbances seen in former athletes. Research in this area will depend on in vivo methods that characterize molecular changes in the brain, linking CTE and other sports-related pathologies with delayed emergence of neuropsychiatric symptoms. In this pilot project we studied former National Football League (NFL) players using new neuroimaging techniques and clinical measures of cognitive functioning. We hypothesized that former NFL players would show molecular and structural changes in medial temporal and parietal lobe structures as well as specific cognitive deficits, namely those of verbal learning and memory. We observed a significant increase in binding of [(11)C]DPA-713 to the translocator protein (TSPO), a marker of brain injury and repair, in several brain regions, such as the supramarginal gyrus and right amygdala, in 9 former NFL players compared to 9 age-matched, healthy controls. We also observed significant atrophy of the right hippocampus. Finally, we report that these same former players had varied performance on a test of verbal learning and memory, suggesting that these molecular and pathologic changes may play a role in cognitive decline. These results suggest that localized brain injury and repair, indicated by increased [(11)C]DPA-713 binding to TSPO, may be linked to history of NFL play. [(11)C]DPA-713 PET is a promising new tool that can be used in future study design to examine further the relationship between TSPO expression in brain injury and repair, selective regional brain atrophy, and the potential link to deficits in verbal learning and memory after NFL play.

}, issn = {1095-953X}, doi = {10.1016/j.nbd.2014.10.019}, author = {Coughlin, Jennifer M and Wang, Yuchuan and Munro, Cynthia A and Ma, Shuangchao and Yue, Chen and Chen, Shaojie and Airan, Raag and Kim, Pearl K and Adams, Ashley V and Garcia, Cinthya and Higgs, Cecilia and Sair, Haris I and Sawa, Akira and Smith, Gwenn and Lyketsos, Constantine G and Caffo, Brian and Kassiou, Michael and Guilarte, Tomas R and Pomper, Martin G} } @article {804, title = {Normalization and extraction of interpretable metrics from raw accelerometry data.}, journal = {Biostatistics}, volume = {15}, year = {2014}, month = {2014 Jan}, pages = {102-16}, abstract = {

We introduce an explicit set of metrics for human activity based on high-density acceleration recordings from a hip-worn tri-axial accelerometer. These metrics are based on two concepts: (i) Time Active, a measure of the length of time when activity is distinguishable from rest and (ii) AI, a measure of the relative amplitude of activity relative to rest. All measurements are normalized (have the same interpretation across subjects and days), easy to explain and implement, and reproducible across platforms and software implementations. Metrics were validated by visual inspection of results and quantitative in-lab replication studies, and by an association study with health outcomes.

}, keywords = {Acceleration, Aged, Baltimore, Cohort Studies, Data Interpretation, Statistical, Female, Humans, Male, Motor Activity}, issn = {1468-4357}, doi = {10.1093/biostatistics/kxt029}, author = {Bai, Jiawei and He, Bing and Shou, Haochang and Zipunnikov, Vadim and Glass, Thomas A and Crainiceanu, Ciprian M} } @article {Bai2014Metrics, title = {Normalization and extraction of interpretable metrics from raw accelerometry data}, journal = {Biostatistics}, volume = {15}, number = {1}, year = {2014}, pages = {102{\textendash}116}, abstract = {

We introduce an explicit set of metrics for human activity based on high-density acceleration recordings from a hip-worn tri-axial accelerometer. These metrics are based on two concepts: (i) Time Active, a measure of the length of time when activity is distinguishable from rest and (ii) AI, a measure of the relative amplitude of activity relative to rest. All measurements are normalized (have the same interpretation across subjects and days), easy to explain and implement, and reproducible across platforms and software implementations. Metrics were validated by visual inspection of results and quantitative in-lab replication studies, and by an association study with health outcomes.

}, keywords = {Activity intensity, Movelets, Movement, Signal processing, Time active, Tri-axial accelerometer}, issn = {14654644}, author = {Bai, Jiawei and He, Bing and Shou, Haochang and Zipunnikov, Vadim and Glass, Thomas A. and Crainiceanu, Ciprian M.} } @article {791, title = {Predicting human movement with multiple accelerometers using movelets.}, journal = {Med Sci Sports Exerc}, volume = {46}, year = {2014}, month = {2014 Sep}, pages = {1859-66}, abstract = {

PURPOSE: The study aims were 1) to develop transparent algorithms that use short segments of training data for predicting activity types and 2) to compare the prediction performance of the proposed algorithms using single accelerometers and multiple accelerometers.

METHODS: Sixteen participants (age, 80.6 yr (4.8 yr); body mass index, 26.1 kg{\textperiodcentered}m (2.5 kg{\textperiodcentered}m)) performed 15 lifestyle activities in the laboratory, each wearing three accelerometers at the right hip and left and right wrists. Triaxial accelerometry data were collected at 80 Hz using ActiGraph GT3X+. Prediction algorithms were developed, which, instead of extracting features, build activity-specific dictionaries composed of short signal segments called movelets. Three alternative approaches were proposed to integrate the information from the multiple accelerometers.

RESULTS: With at most several seconds of training data per activity, the prediction accuracy at the second-level temporal resolution was very high for lying, standing, normal/fast walking, and standing up from a chair (the median prediction accuracy ranged from 88.2\% to 99.9\% on the basis of the single-accelerometer movelet approach). For these activities, wrist-worn accelerometers performed almost as well as hip-worn accelerometers (the median difference in accuracy between wrist and hip ranged from -2.7\% to 5.8\%). Modest improvements in prediction accuracy were achieved by integrating information from multiple accelerometers.

DISCUSSION AND CONCLUSIONS: It is possible to achieve high prediction accuracy at the second-level temporal resolution with very limited training data. To increase prediction accuracy from the simultaneous use of multiple accelerometers, a careful selection of integrative approaches is required.

}, issn = {1530-0315}, doi = {10.1249/MSS.0000000000000285}, author = {He, Bing and Bai, Jiawei and Zipunnikov, Vadim V and Koster, Annemarie and Caserotti, Paolo and Lange-Maia, Brittney and Glynn, Nancy W and Harris, Tamara B and Crainiceanu, Ciprian M} } @article {787, title = {Quantifying the lifetime circadian rhythm of physical activity: a covariate-dependent functional approach.}, journal = {Biostatistics}, year = {2014}, month = {2014 Oct 30}, abstract = {

Objective measurement of physical activity using wearable devices such as accelerometers may provide tantalizing new insights into the association between activity and health outcomes. Accelerometers can record quasi-continuous activity information for many days and for hundreds of individuals. For example, in the Baltimore Longitudinal Study on Aging physical activity was recorded every minute for [Formula: see text] adults for an average of [Formula: see text] days per adult. An important scientific problem is to separate and quantify the systematic and random circadian patterns of physical activity as functions of time of day, age, and gender. To capture the systematic circadian pattern, we introduce a practical bivariate smoother and two crucial innovations: (i) estimating the smoothing parameter using leave-one-subject-out cross validation to account for within-subject correlation and (ii) introducing fast computational techniques that overcome problems both with the size of the data and with the cross-validation approach to smoothing. The age-dependent random patterns are analyzed by a new functional principal component analysis that incorporates both covariate dependence and multilevel structure. For the analysis, we propose a practical and very fast trivariate spline smoother to estimate covariate-dependent covariances and their spectra. Results reveal several interesting, previously unknown, circadian patterns associated with human aging and gender.

}, issn = {1468-4357}, doi = {10.1093/biostatistics/kxu045}, author = {Xiao, Luo and Huang, Lei and Schrack, Jennifer A and Ferrucci, Luigi and Zipunnikov, Vadim and Crainiceanu, Ciprian M} } @article {818, title = {Reduction of motion-related artifacts in resting state fMRI using aCompCor.}, journal = {Neuroimage}, volume = {96}, year = {2014}, month = {2014 Aug 1}, pages = {22-35}, abstract = {

Recent studies have illustrated that motion-related artifacts remain in resting-state fMRI (rs-fMRI) data even after common corrective processing procedures have been applied, but the extent to which head motion distorts the data may be modulated by the corrective approach taken. We compare two different methods for estimating nuisance signals from tissues not expected to exhibit BOLD fMRI signals of neuronal origin: 1) the more commonly used mean signal method and 2) the principal components analysis approach (aCompCor: Behzadi et al., 2007). Further, we investigate the added benefit of "scrubbing" (Power et al., 2012) following both methods. We demonstrate that the use of aCompCor removes motion artifacts more effectively than tissue-mean signal regression. In addition, inclusion of more components from anatomically defined regions of no interest better mitigates motion-related artifacts and improves the specificity of functional connectivity estimates. While scrubbing further attenuates motion-related artifacts when mean signals are used, scrubbing provides no additional benefit in terms of motion artifact reduction or connectivity specificity when using aCompCor.

}, issn = {1095-9572}, doi = {10.1016/j.neuroimage.2014.03.028}, author = {Muschelli, John and Nebel, Mary Beth and Caffo, Brian S and Barber, Anita D and Pekar, James J and Mostofsky, Stewart H} } @article {792, title = {Shrinkage prediction of seed-voxel brain connectivity using resting state fMRI.}, journal = {Neuroimage}, volume = {102 Pt 2}, year = {2014}, month = {2014 Nov 15}, pages = {938-44}, abstract = {

Resting-state functional magnetic resonance imaging (rs-fMRI) is used to investigate synchronous activations in spatially distinct regions of the brain, which are thought to reflect functional systems supporting cognitive processes. Analyses are often performed using seed-based correlation analysis, allowing researchers to explore functional connectivity between data in a seed region and the rest of the brain. Using scan-rescan rs-fMRI data, we investigate how well the subject-specific seed-based correlation map from the second replication of the study can be predicted using data from the first replication. We show that one can dramatically improve prediction of subject-specific connectivity by borrowing strength from the group correlation map computed using all other subjects in the study. Even more surprisingly, we found that the group correlation map provided a better prediction of a subject{\textquoteright}s connectivity than the individual{\textquoteright}s own data. While further discussion and experimentation are required to understand how this can be used in practice, results indicate that shrinkage-based methods that borrow strength from the population mean should play a role in rs-fMRI data analysis.

}, issn = {1095-9572}, doi = {10.1016/j.neuroimage.2014.05.043}, author = {Shou, Haochang and Eloyan, Ani and Nebel, Mary Beth and Mejia, Amanda and Pekar, James J and Mostofsky, Stewart and Caffo, Brian and Lindquist, Martin A and Crainiceanu, Ciprian M} } @article {796, title = {Smooth Scalar-on-Image Regression via Spatial Bayesian Variable Selection.}, journal = {J Comput Graph Stat}, volume = {23}, year = {2014}, month = {2014 Jan 1}, pages = {46-64}, abstract = {

We develop scalar-on-image regression models when images are registered multidimensional manifolds. We propose a fast and scalable Bayes inferential procedure to estimate the image coefficient. The central idea is the combination of an Ising prior distribution, which controls a latent binary indicator map, and an intrinsic Gaussian Markov random field, which controls the smoothness of the nonzero coefficients. The model is fit using a single-site Gibbs sampler, which allows fitting within minutes for hundreds of subjects with predictor images containing thousands of locations. The code is simple and is provided in less than one page in the Appendix. We apply this method to a neuroimaging study where cognitive outcomes are regressed on measures of white matter microstructure at every voxel of the corpus callosum for hundreds of subjects.

}, issn = {1061-8600}, doi = {10.1080/10618600.2012.743437}, author = {Goldsmith, Jeff and Huang, Lei and Crainiceanu, Ciprian M} } @article {786, title = {Statistical normalization techniques for magnetic resonance imaging.}, journal = {Neuroimage Clin}, volume = {6}, year = {2014}, month = {2014}, pages = {9-19}, abstract = {

While computed tomography and other imaging techniques are measured in absolute units with physical meaning, magnetic resonance images are expressed in arbitrary units that are difficult to interpret and differ between study visits and subjects. Much work in the image processing literature on intensity normalization has focused on histogram matching and other histogram mapping techniques, with little emphasis on normalizing images to have biologically interpretable units. Furthermore, there are no formalized principles or goals for the crucial comparability of image intensities within and across subjects. To address this, we propose a set of criteria necessary for the normalization of images. We further propose simple and robust biologically motivated normalization techniques for multisequence brain imaging that have the same interpretation across acquisitions and satisfy the proposed criteria. We compare the performance of different normalization methods in thousands of images of patients with Alzheimer{\textquoteright}s disease, hundreds of patients with multiple sclerosis, and hundreds of healthy subjects obtained in several different studies at dozens of imaging centers.

}, issn = {2213-1582}, doi = {10.1016/j.nicl.2014.08.008}, author = {Shinohara, Russell T and Sweeney, Elizabeth M and Goldsmith, Jeff and Shiee, Navid and Mateen, Farrah J and Calabresi, Peter A and Jarso, Samson and Pham, Dzung L and Reich, Daniel S and Crainiceanu, Ciprian M} } @article {789, title = {Structured functional principal component analysis.}, journal = {Biometrics}, year = {2014}, month = {2014 Oct 18}, abstract = {

Motivated by modern observational studies, we introduce a class of functional models that expand nested and crossed designs. These models account for the natural inheritance of the correlation structures from sampling designs in studies where the fundamental unit is a function or image. Inference is based on functional quadratics and their relationship with the underlying covariance structure of the latent processes. A computationally fast and scalable estimation procedure is developed for high-dimensional data. Methods are used in applications including high-frequency accelerometer data for daily activity, pitch linguistic data for phonetic analysis, and EEG data for studying electrical brain activity during sleep.

}, issn = {1541-0420}, doi = {10.1111/biom.12236}, author = {Shou, Haochang and Zipunnikov, Vadim and Crainiceanu, Ciprian M and Greven, Sonja} } @article {820, title = {Successful implementation of a unit-based quality nurse to reduce central line-associated bloodstream infections.}, journal = {Am J Infect Control}, volume = {42}, year = {2014}, month = {2014 Feb}, pages = {139-43}, abstract = {

BACKGROUND: Central line (CL)-associated bloodstream infections (CLABSI) are an important cause of patient morbidity and mortality. Novel strategies to prevent CLABSI are needed.

METHODS: We described a quasiexperimental study to examine the effect of the presence of a unit-based quality nurse (UQN) dedicated to perform patient safety and infection control activities with a focus on CLABSI prevention in a surgical intensive care unit (SICU).

RESULTS: From July 2008 to March 2012, there were 3,257 SICU admissions; CL utilization ratio was 0.74 (18,193 CL-days/24,576 patient-days). The UQN program began in July 2010; the nurse was present for 30\% (193/518) of the days of the intervention period of July 2010 to March 2012. The average CLABSI rate was 5.0 per 1,000 CL-days before the intervention and 1.5 after the intervention and decreased by 5.1\% (P = .005) for each additional 1\% of days of the month that the UQN was present, even after adjusting for CLABSI rates in other adult intensive care units, time, severity of illness, and Comprehensive Unit-based Safety Program participation (5.1\%, P = .004). Approximately 11.4 CLABSIs were prevented.

CONCLUSION: The presence of a UQN dedicated to perform infection control activities may be an effective strategy for CLABSI reduction.

}, keywords = {Adult, Catheter-Related Infections, Catheterization, Central Venous, Humans, Infection Control, Intensive Care Units, Nurses, Quality Control, Quality of Health Care}, issn = {1527-3296}, doi = {10.1016/j.ajic.2013.08.006}, author = {Thom, Kerri A and Li, Shanshan and Custer, Melissa and Preas, Michael Anne and Rew, Cindy D and Cafeo, Christina and Leekha, Surbhi and Caffo, Brian S and Scalea, Thomas M and Lissauer, Matthew E} } @article {788, title = {A unifying framework for marginalized random intercept models of correlated binary outcomes.}, journal = {Int Stat Rev}, volume = {82}, year = {2014}, month = {2014 Aug}, pages = {275-295}, abstract = {

We demonstrate that many current approaches for marginal modeling of correlated binary outcomes produce likelihoods that are equivalent to the copula-based models herein. These general copula models of underlying latent threshold random variables yield likelihood-based models for marginal fixed effects estimation and interpretation in the analysis of correlated binary data with exchangeable correlation structures. Moreover, we propose a nomenclature and set of model relationships that substantially elucidates the complex area of marginalized random intercept models for binary data. A diverse collection of didactic mathematical and numerical examples are given to illustrate concepts.

}, issn = {0306-7734}, doi = {10.1111/insr.12035}, author = {Swihart, Bruce J and Caffo, Brian S and Crainiceanu, Ciprian M} } @article {806, title = {Acute lesions that impair affective empathy.}, journal = {Brain}, volume = {136}, year = {2013}, month = {2013 Aug}, pages = {2539-49}, abstract = {

Functional imaging studies of healthy participants and previous lesion studies have provided evidence that empathy involves dissociable cognitive functions that rely on at least partially distinct neural networks that can be individually impaired by brain damage. These studies converge in support of the proposal that affective empathy--making inferences about how another person feels--engages at least the following areas: prefrontal cortex, orbitofrontal gyrus, anterior insula, anterior cingulate cortex, temporal pole, amygdala and temporoparietal junction. We hypothesized that right-sided lesions to any one of these structures, except temporoparietal junction, would cause impaired affective empathy (whereas bilateral damage to temporoparietal junction would be required to disrupt empathy). We studied 27 patients with acute right hemisphere ischaemic stroke and 24 neurologically intact inpatients on a test of affective empathy. Acute impairment of affective empathy was associated with infarcts in the hypothesized network, particularly temporal pole and anterior insula. All patients with impaired affective empathy were also impaired in comprehension of affective prosody, but many patients with impairments in prosodic comprehension had spared affective empathy. Patients with impaired affective empathy were older, but showed no difference in performance on tests of hemispatial neglect, volume of infarct or sex distribution compared with patients with intact affective empathy.

}, keywords = {Adult, Aged, Brain, Brain Ischemia, brain mapping, Cognition, Emotions, Empathy, Female, Functional Laterality, Humans, Male, Middle Aged, Nerve Net, Social Perception, Stroke}, issn = {1460-2156}, doi = {10.1093/brain/awt177}, author = {Leigh, Richard and Oishi, Kenichi and Hsu, John and Lindquist, Martin and Gottesman, Rebecca F and Jarso, Samson and Crainiceanu, Ciprian and Mori, Susumu and Hillis, Argye E} } @article {828, title = {Axial 3D gradient-echo imaging for improved multiple sclerosis lesion detection in the cervical spinal cord at 3T.}, journal = {Neuroradiology}, volume = {55}, year = {2013}, month = {2013 Mar}, pages = {431-9}, abstract = {

INTRODUCTION: In multiple sclerosis (MS), spinal cord imaging can help in diagnosis and follow-up evaluation. However, spinal cord magnetic resonance imaging (MRI) is technically challenging, and image quality, particularly in the axial plane, is typically poor compared to brain MRI. Because gradient-recalled echo (GRE) images might offer improved contrast resolution within the spinal cord at high magnetic field strength, both without and with a magnetization transfer prepulse, we compared them to T2-weighted fast-spin-echo (T2-FSE) images for the detection of MS lesions in the cervical cord at 3T.

METHODS: On a clinical 3T MRI scanner, we studied 62 MS cases and 19 healthy volunteers. Axial 3D GRE sequences were performed without and with off-resonance radiofrequency irradiation. To mimic clinical practice, all images were evaluated in conjunction with linked images from a sagittal short tau inversion recovery scan, which is considered the gold standard for lesion detection in MS. Two experienced observers recorded image quality, location and size of focal lesions, atrophy, swelling, and diffuse signal abnormality independently at first and then in consensus.

RESULTS: The number and volume of lesions detected with high confidence was more than three times as high on both GRE sequences compared to T2-FSE (p < 0.0001). Approximately 5 \% of GRE scans were affected by artifacts that interfered with image interpretation, not significantly different from T2W-FSE.

CONCLUSIONS: Axial 3D GRE sequences are useful for MS lesion detection when compared to 2D T2-FSE sequences in the cervical spinal cord at 3T and should be considered when examining intramedullary spinal cord lesions.

}, keywords = {Adult, Aged, Algorithms, Cervical Vertebrae, Echo-Planar Imaging, Female, Humans, Image Enhancement, Image Interpretation, Computer-Assisted, Imaging, Three-Dimensional, Male, Middle Aged, Multiple Sclerosis, Reproducibility of Results, Sensitivity and Specificity, Spinal Cord}, issn = {1432-1920}, doi = {10.1007/s00234-012-1118-5}, author = {Ozturk, Arzu and Aygun, Nafi and Smith, Seth A and Caffo, Brian and Calabresi, Peter A and Reich, Daniel S} } @article {807, title = {Bayesian scalar-on-image regression with application to association between intracranial DTI and cognitive outcomes.}, journal = {Neuroimage}, volume = {83}, year = {2013}, month = {2013 Dec}, pages = {210-23}, abstract = {

Diffusion tensor imaging (DTI) measures water diffusion within white matter, allowing for in vivo quantification of brain pathways. These pathways often subserve specific functions, and impairment of those functions is often associated with imaging abnormalities. As a method for predicting clinical disability from DTI images, we propose a hierarchical Bayesian "scalar-on-image" regression procedure. Our procedure introduces a latent binary map that estimates the locations of predictive voxels and penalizes the magnitude of effect sizes in these voxels, thereby resolving the ill-posed nature of the problem. By inducing a spatial prior structure, the procedure yields a sparse association map that also maintains spatial continuity of predictive regions. The method is demonstrated on a simulation study and on a study of association between fractional anisotropy and cognitive disability in a cross-sectional sample of 135 multiple sclerosis patients.

}, issn = {1095-9572}, doi = {10.1016/j.neuroimage.2013.06.020}, author = {Huang, Lei and Goldsmith, Jeff and Reiss, Philip T and Reich, Daniel S and Crainiceanu, Ciprian M} } @article {799, title = {Body composition and arsenic metabolism: a cross-sectional analysis in the Strong Heart Study.}, journal = {Environ Health}, volume = {12}, year = {2013}, month = {2013}, pages = {107}, abstract = {

OBJECTIVE: The objective of this study was to evaluate the association between measures of body composition and patterns of urine arsenic metabolites in the 1989-1991 baseline visit of the Strong Heart Study, a cardiovascular disease cohort of adults recruited from rural communities in Arizona, Oklahoma, North Dakota and South Dakota.

METHODS: We evaluated 3,663 Strong Heart Study participants with urine arsenic species above the limit of detection and no missing data on body mass index, \% body fat and fat free mass measured by bioelectrical impedance, waist circumference and other variables. We summarized urine arsenic species patterns as the relative contribution of inorganic (iAs), methylarsonate (MMA) and dimethylarsinate (DMA) species to their sum. We modeled the associations of \% arsenic species biomarkers with body mass index, \% body fat, fat free mass, and waist circumference categories in unadjusted regression models and in models including all measures of body composition. We also considered adjustment for arsenic exposure and demographics.

RESULTS: Increasing body mass index was associated with higher mean \% DMA and lower mean \% MMA before and after adjustment for sociodemographic variables, arsenic exposure, and for other measures of body composition. In unadjusted linear regression models, \% DMA was 2.4 (2.1, 2.6) \% higher per increase in body mass index category (< 25, >=25 \& <30, >=30 \& <35, >=35 kg/m2), and \% MMA was 1.6 (1.4, 1.7) \% lower. Similar patterns were observed for \% body fat, fat free mass, and waist circumference measures in unadjusted models and in models adjusted for potential confounders, but the associations were largely attenuated or disappeared when adjusted for body mass index.

CONCLUSION: Measures of body size, especially body mass index, are associated with arsenic metabolism biomarkers. The association may be related to adiposity, fat free mass or body size. Future epidemiologic studies of arsenic should consider body mass index as a potential modifier for arsenic-related health effects.

}, issn = {1476-069X}, doi = {10.1186/1476-069X-12-107}, author = {Gribble, Matthew O and Crainiceanu, Ciprian M and Howard, Barbara V and Umans, Jason G and Francesconi, Kevin A and Goessler, Walter and Zhang, Ying and Silbergeld, Ellen K and Guallar, Eliseo and Navas-Acien, Ana} } @article {810, title = {Combining hidden Markov models for comparing the dynamics of multiple sleep electroencephalograms.}, journal = {Stat Med}, volume = {32}, year = {2013}, month = {2013 Aug 30}, pages = {3342-56}, abstract = {

In this manuscript, we consider methods for the analysis of populations of electroencephalogram signals during sleep for the study of sleep disorders using hidden Markov models (HMMs). Notably, we propose an easily implemented method for simultaneously modeling multiple time series that involve large amounts of data. We apply these methods to study sleep-disordered breathing (SDB) in the Sleep Heart Health Study (SHHS), a landmark study of SDB and cardiovascular consequences. We use the entire, longitudinally collected, SHHS cohort to develop HMM population parameters, which we then apply to obtain subject-specific Markovian predictions. From these predictions, we create several indices of interest, such as transition frequencies between latent states. Our HMM analysis of electroencephalogram signals uncovers interesting findings regarding differences in brain activity during sleep between those with and without SDB. These findings include stability of the percent time spent in HMM latent states across matched diseased and non-diseased groups and differences in the rate of transitioning.

}, keywords = {Data Interpretation, Statistical, Electroencephalography, Female, Humans, Longitudinal Studies, Male, Markov Chains, Middle Aged, Models, Statistical, Sleep Apnea Syndromes}, issn = {1097-0258}, doi = {10.1002/sim.5747}, author = {Langrock, Roland and Swihart, Bruce J and Caffo, Brian S and Punjabi, Naresh M and Crainiceanu, Ciprian M} } @article {823, title = {Comparison of total hospital-acquired bloodstream infections to central line-associated bloodstream infections and implications for outcome measures in infection control.}, journal = {Infect Control Hosp Epidemiol}, volume = {34}, year = {2013}, month = {2013 Sep}, pages = {984-6}, abstract = {

The validity of the central line-associated bloodstream infection (CLABSI) measure is compromised by subjectivity. We observed significant decreases in both CLABSIs and total hospital-acquired bloodstream infections (BSIs) following a CLABSI prevention intervention in adult intensive care units. Total hospital-acquired BSIs could be explored as an adjunct, objective CLABSI measure.

}, keywords = {Adult, Catheter-Related Infections, Catheterization, Central Venous, Cross Infection, Humans, Intensive Care Units, Longitudinal Studies, Tertiary Care Centers}, issn = {1559-6834}, doi = {10.1086/671730}, author = {Leekha, Surbhi and Li, Shanshan and Thom, Kerri A and Preas, Michael Anne and Caffo, Brian S and Morgan, Daniel J and Harris, Anthony D} } @article {684, title = {Corrected confidence bands for functional data using principal components.}, journal = {Biometrics}, volume = {69}, year = {2013}, month = {2013 Mar}, pages = {41-51}, abstract = {

Functional principal components (FPC) analysis is widely used to decompose and express functional observations. Curve estimates implicitly condition on basis functions and other quantities derived from FPC decompositions; however these objects are unknown in practice. In this article, we propose a method for obtaining correct curve estimates by accounting for uncertainty in FPC decompositions. Additionally, pointwise and simultaneous confidence intervals that account for both model- and decomposition-based variability are constructed. Standard mixed model representations of functional expansions are used to construct curve estimates and variances conditional on a specific decomposition. Iterated expectation and variance formulas combine model-based conditional estimates across the distribution of decompositions. A bootstrap procedure is implemented to understand the uncertainty in principal component decomposition quantities. Our method compares favorably to competing approaches in simulation studies that include both densely and sparsely observed functions. We apply our method to sparse observations of CD4 cell counts and to dense white-matter tract profiles. Code for the analyses and simulations is publicly available, and our method is implemented in the R package refund on CRAN.

}, keywords = {Brain, CD4 Lymphocyte Count, Computer Simulation, Confidence Intervals, HIV, HIV Infections, Humans, Magnetic Resonance Imaging, Models, Statistical, Multiple Sclerosis, Principal Component Analysis}, issn = {1541-0420}, doi = {10.1111/j.1541-0420.2012.01808.x}, author = {Goldsmith, J and Greven, S and Crainiceanu, C} } @article {824, title = {A decision-theory approach to interpretable set analysis for high-dimensional data.}, journal = {Biometrics}, volume = {69}, year = {2013}, month = {2013 Sep}, pages = {614-23}, abstract = {

A key problem in high-dimensional significance analysis is to find pre-defined sets that show enrichment for a statistical signal of interest; the classic example is the enrichment of gene sets for differentially expressed genes. Here, we propose a new decision-theory approach to the analysis of gene sets which focuses on estimating the fraction of non-null variables in a set. We introduce the idea of "atoms," non-overlapping sets based on the original pre-defined set annotations. Our approach focuses on finding the union of atoms that minimizes a weighted average of the number of false discoveries and missed discoveries. We introduce a new false discovery rate for sets, called the atomic false discovery rate (afdr), and prove that the optimal estimator in our decision-theory framework is to threshold the afdr. These results provide a coherent and interpretable framework for the analysis of sets that addresses the key issues of overlapping annotations and difficulty in interpreting p values in both competitive and self-contained tests. We illustrate our method and compare it to a popular existing method using simulated examples, as well as gene-set and brain ROI data analyses.

}, keywords = {Algorithms, Bayes Theorem, Biometry, Brain, Computer Simulation, Data Interpretation, Statistical, Decision Theory, Functional Neuroimaging, Gene Expression Profiling, Genomics, Humans, Magnetic Resonance Imaging, Models, Statistical, Oligonucleotide Array Sequence Analysis}, issn = {1541-0420}, doi = {10.1111/biom.12060}, author = {Boca, Simina M and Bravo, H{\'e}ctor C{\'e}orrada and Caffo, Brian and Leek, Jeffrey T and Parmigiani, Giovanni} } @article {838, title = {Detecting functional connectivity change points for single-subject fMRI data.}, journal = {Front Comput Neurosci}, volume = {7}, year = {2013}, month = {2013}, pages = {143}, abstract = {

Recently in functional magnetic resonance imaging (fMRI) studies there has been an increased interest in understanding the dynamic manner in which brain regions communicate with one another, as subjects perform a set of experimental tasks or as their psychological state changes. Dynamic Connectivity Regression (DCR) is a data-driven technique used for detecting temporal change points in functional connectivity between brain regions where the number and location of the change points are unknown a priori. After finding the change points, DCR estimates a graph or set of relationships between the brain regions for data that falls between pairs of change points. In previous work, the method was predominantly validated using multi-subject data. In this paper, we concentrate on single-subject data and introduce a new DCR algorithm. The new algorithm increases accuracy for individual subject data with a small number of observations and reduces the number of false positives in the estimated undirected graphs. We also introduce a new Likelihood Ratio test for comparing sparse graphs across (or within) subjects; thus allowing us to determine whether data should be combined across subjects. We perform an extensive simulation analysis on vector autoregression (VAR) data as well as to an fMRI data set from a study (n = 23) of a state anxiety induction using a socially evaluative threat challenge. The focus on single-subject data allows us to study the variation between individuals and may provide us with a deeper knowledge of the workings of the brain.

}, issn = {1662-5188}, doi = {10.3389/fncom.2013.00143}, author = {Cribben, Ivor and Wager, Tor D and Lindquist, Martin A} } @article {829, title = {Developmental changes in within- and between-network connectivity between late childhood and adulthood.}, journal = {Neuropsychologia}, volume = {51}, year = {2013}, month = {2013 Jan}, pages = {156-67}, abstract = {

A number of behavioral changes occur between late childhood and adulthood, including maturation of social cognition, reward receptivity, impulsiveness, risk-taking and cognitive control. Although some of these abilities show linear improvements with age, some abilities may temporarily worsen, reflecting both the restructuring and/or strengthening of connections within some brain systems. The current study uses resting state functional connectivity to examine developmental differences between late childhood and adulthood in task positive (TP) regions, which play a role in cognitive control functions, and task negative (TN) regions, which play a role in social cognition, self-referential, and internally-directed thought. Within the TP network, developmental differences in connectivity were found with the left dorsolateral prefrontal cortex. Within the TN network, developmental differences in connectivity were found with a broad area of the medial prefrontal cortex and the right parahippocampal gyrus. Connections between the two networks also showed significant developmental differences. Stronger anticorrelations were found in the TN maps of the adult group for the right anterior insula/inferior frontal gyrus, bilateral anterior inferior parietal lobule, bilateral superior parietal lobule and an anterior portion of the right posterior cingulate cortex. There was a significant brain-behavior relationship between the strength of anticorrelation in these regions and inhibitory control performance on two Go/No-go tasks suggesting that the development of anticorrelations between late childhood and adulthood supports mature inhibitory control. Overall, maturation of these networks occurred in specific regions which are associated with cognitive control of goal-directed behavior, including those involved in working memory, social cognition, and inhibitory control.

}, keywords = {Adolescent, Adult, Age Factors, Analysis of Variance, Brain, brain mapping, Child, Child Development, Cognition, Female, Humans, Image Processing, Computer-Assisted, Inhibition (Psychology), Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Neuropsychological Tests, Oxygen, Reaction Time, Young Adult}, issn = {1873-3514}, doi = {10.1016/j.neuropsychologia.2012.11.011}, author = {Barber, Anita D and Caffo, Brian S and Pekar, James J and Mostofsky, Stewart H} } @article {826, title = {Effects of working memory demand on neural mechanisms of motor response selection and control.}, journal = {J Cogn Neurosci}, volume = {25}, year = {2013}, month = {2013 Aug}, pages = {1235-48}, abstract = {

Inhibitory control commonly recruits a number of frontal regions: pre-supplementary motor area (pre-SMA), frontal eye fields (FEFs), and right-lateralized posterior inferior frontal gyrus (IFG), dorsal anterior insula (DAI), dorsolateral prefrontal cortex (DLPFC), and inferior frontal junction (IFJ). These regions may directly implement inhibitory motor control or may be more generally involved in executive control functions. Two go/no-go tasks were used to distinguish regions specifically recruited for inhibition from those that additionally show increased activity with working memory demand. The pre-SMA and IFG were recruited for inhibition in both tasks and did not have greater activation for working memory demand on no-go trials, consistent with a role in inhibitory control. Activation in pre-SMA also responded to response selection demand and was increased with working memory on go trials specifically. The bilateral FEF and right DAI were commonly active for no-go trials. The FEF was also recruited to a greater degree with working memory demand on go trials and may bias top-down information when stimulus-response mappings change. The DAI, additionally responded to increased working memory demand on both go and no-go trials and may be involved in accessing sustained task information, alerting, or autonomic changes when cognitive demands increase. DLPFC activation was consistent with a role in working memory retrieval on both go and no-go trials. The inferior frontal junction, on the other hand, had greater activation with working memory specifically for no-go trials and may detect salient stimuli when the task requires frequent updating of working memory representations.

}, keywords = {Adult, Brain, brain mapping, Choice Behavior, Female, Humans, Image Processing, Computer-Assisted, Inhibition (Psychology), Magnetic Resonance Imaging, Male, Memory, Short-Term, Motor Activity, Neuropsychological Tests, Oxygen, Reaction Time, Young Adult}, issn = {1530-8898}, doi = {10.1162/jocn_a_00394}, author = {Barber, Anita D and Caffo, Brian S and Pekar, James J and Mostofsky, Stewart H} } @article {800, title = {Hierarchical Adaptive Regression Kernels for Regression with Functional Predictors.}, journal = {J Comput Graph Stat}, volume = {22}, year = {2013}, month = {2013}, abstract = {

We propose a new method for regression using a parsimonious and scientifically interpretable representation of functional predictors. Our approach is designed for data that exhibit features such as spikes, dips, and plateaus whose frequency, location, size, and shape varies stochastically across subjects. We propose Bayesian inference of the joint functional and exposure models, and give a method for efficient computation. We contrast our approach with existing state-of-the-art methods for regression with functional predictors, and show that our method is more effective and efficient for data that include features occurring at varying locations. We apply our methodology to a large and complex dataset from the Sleep Heart Health Study, to quantify the association between sleep characteristics and health outcomes. Software and technical appendices are provided in online supplemental materials.

}, issn = {1061-8600}, doi = {10.1080/10618600.2012.694765}, author = {Woodard, Dawn B and Crainiceanu, Ciprian and Ruppert, David} } @article {809, title = {In vivo identification of morphologic retinal abnormalities in neuromyelitis optica.}, journal = {Neurology}, volume = {80}, year = {2013}, month = {2013 Apr 9}, pages = {1406-14}, abstract = {

OBJECTIVE: To assess eyes with neuromyelitis optica (NMO) for morphologic retinal abnormalities utilizing high-definition optical coherence tomography (OCT) imaging.

METHODS: In this cross-sectional study, 39 patients with NMO spectrum disorders and 39 age- and sex-matched healthy controls underwent spectral-domain OCT and visual function testing.

RESULTS: Microcystic macular edema (MME) of the inner nuclear layer (INL) was identified in 10 of 39 patients (26\%) and was exclusively found in eyes with a history of optic neuritis (ON). MME eyes had lower high- and low-contrast letter-acuity scores (100\%: p = 0.002; 2.5\%: p = 0.002; 1.25\%: p = 0.004), lower peripapillary retinal nerve fiber layer (RNFL) thickness (p = 0.04), lower macular RNFL thickness (p = 0.004), lower ganglion cell layer + inner plexiform layer (GCIP) thickness (p = 0.007), higher INL thickness (p < 0.001), and a greater number of ON episodes (p = 0.008) relative to non-MME eyes with a history of ON. After adjusting for history of multiple ON episodes, these findings remained significant for macular-RNFL thickness (p = 0.03), INL thickness (p < 0.001), and 100\% and 2.5\% contrast letter-acuity scores (p = 0.008 and p = 0.03, respectively). NMO spectrum eyes without ON history had lower macular RNFL thickness (p = 0.003), GCIP thickness (p = 0.002), outer nuclear layer thickness (p = 0.02), and low-contrast letter-acuity scores (2.5\%: p = 0.03; 1.25\%: p = 0.002) compared to healthy controls.

CONCLUSIONS: We have identified a pattern of retinal morphologic abnormalities in NMO that is associated with severe retinal axonal and neuronal loss and corresponding visual disability. MME may contribute to poor visual outcomes following NMO-associated ON or alternatively represent a marker of ON severity. Additionally, our results support that subclinical involvement of the anterior visual pathway may occur in NMO spectrum disorders.

}, keywords = {Adolescent, Adult, Aged, Aquaporin 4, Autoantibodies, Case-Control Studies, Chi-Square Distribution, Female, Humans, Macular Edema, Male, Middle Aged, Nerve Fibers, Neuromyelitis Optica, Retina, Tomography, Optical Coherence, Vision Tests, Visual Acuity, Young Adult}, issn = {1526-632X}, doi = {10.1212/WNL.0b013e31828c2f7a}, author = {Sotirchos, Elias S and Saidha, Shiv and Byraiah, Gita and Mealy, Maureen A and Ibrahim, Mohamed A and Sepah, Yasir Jamal and Newsome, Scott D and Ratchford, John N and Frohman, Elliot M and Balcer, Laura J and Crainiceanu, Ciprian M and Nguyen, Quan Dong and Levy, Michael and Calabresi, Peter A} } @article {808, title = {Ironing out the statistical wrinkles in "ten ironic rules".}, journal = {Neuroimage}, volume = {81}, year = {2013}, month = {2013 Nov 1}, pages = {499-502}, abstract = {

The article "Ten ironic rules for non-statistical reviewers" (Friston, 2012) shares some commonly heard frustrations about the peer-review process that all researchers can identify with. Though we found the article amusing, we have some concerns about its description of a number of statistical issues. In this commentary we address these issues, as well as the premise of the article.

}, keywords = {Neuroimaging, Peer Review, Research, Research Design, Statistics as Topic}, issn = {1095-9572}, doi = {10.1016/j.neuroimage.2013.02.056}, author = {Lindquist, Martin A and Caffo, Brian and Crainiceanu, Ciprian} } @article {825, title = {Isoosmolar enemas demonstrate preferential gastrointestinal distribution, safety, and acceptability compared with hyperosmolar and hypoosmolar enemas as a potential delivery vehicle for rectal microbicides.}, journal = {AIDS Res Hum Retroviruses}, volume = {29}, year = {2013}, month = {2013 Nov}, pages = {1487-95}, abstract = {

Rectally applied antiretroviral microbicides for preexposure prophylaxis (PrEP) of HIV infection are currently in development. Since enemas (rectal douches) are commonly used by men who have sex with men prior to receptive anal intercourse, a microbicide enema could enhance PrEP adherence by fitting seamlessly within the usual sexual practices. We assessed the distribution, safety, and acceptability of three enema types-hyperosmolar (Fleet), hypoosmolar (distilled water), and isoosmolar (Normosol-R)-in a crossover design. Nine men received each enema type in random order. Enemas were radiolabeled [(99m)Tc-diethylene triamine pentaacetic acid (DTPA)] to assess enema distribution in the colon using single photon emission computed tomography/computed tomography (SPECT/CT) imaging. Plasma (99m)Tc-DTPA indicated mucosal permeability. Sigmoidoscopic colon tissue biopsies were taken to assess injury as well as tissue penetration of the (99m)Tc-DTPA. Acceptability was assessed after each product use and at the end of the study. SPECT/CT imaging showed that the isoosmolar enema had greater proximal colonic distribution (up to the splenic flexure) and greater luminal and colon tissue concentrations of (99m)Tc-DTPA when compared to the other enemas (p<0.01). Colon biopsies also showed that only the hyperosmolar enema caused sloughing of the colonic epithelium (p<0.05). In permeability testing, the hypoosmolar enema had higher plasma (99m)Tc-DTPA 24-h area under the concentration-time curve and peak concentration compared to the hyperosmolar and isoosmolar enemas, respectively. Acceptability was generally good with no clear preferences among the three enema types. The isoosmolar enema was superior or similar to the other enemas in all categories and is a good candidate for further development as a rectal microbicide vehicle.

}, keywords = {Anti-Infective Agents, Biopsy, Colon, Sigmoid, Enema, HIV Infections, Humans, Intestinal Mucosa, Male, Patient Acceptance of Health Care, Solutions, Tomography, Emission-Computed, Single-Photon}, issn = {1931-8405}, doi = {10.1089/AID.2013.0189}, author = {Leyva, Francisco J and Bakshi, Rahul P and Fuchs, Edward J and Li, Liye and Caffo, Brian S and Goldsmith, Arthur J and Ventuneac, Ana and Carballo-Di{\'e}guez, Alex and Du, Yong and Leal, Jeffrey P and Lee, Linda A and Torbenson, Michael S and Hendrix, Craig W} } @article {812, title = {Likelihood-based population independent component analysis.}, journal = {Biostatistics}, volume = {14}, year = {2013}, month = {2013 Jul}, pages = {514-27}, abstract = {

Independent component analysis (ICA) is a widely used technique for blind source separation, used heavily in several scientific research areas including acoustics, electrophysiology, and functional neuroimaging. We propose a scalable two-stage iterative true group ICA methodology for analyzing population level functional magnetic resonance imaging (fMRI) data where the number of subjects is very large. The method is based on likelihood estimators of the underlying source densities and the mixing matrix. As opposed to many commonly used group ICA algorithms, the proposed method does not require significant data reduction by a 2-fold singular value decomposition. In addition, the method can be applied to a large group of subjects since the memory requirements are not restrictive. The performance of our approach is compared with a commonly used group ICA algorithm via simulation studies. Furthermore, the proposed method is applied to a large collection of resting state fMRI datasets. The results show that established brain networks are well recovered by the proposed algorithm.

}, keywords = {Adult, Algorithms, Attention Deficit Disorder with Hyperactivity, Biostatistics, Brain, Child, Computer Simulation, Databases, Factual, Humans, Imaging, Three-Dimensional, Likelihood Functions, Magnetic Resonance Imaging, Principal Component Analysis, Statistics, Nonparametric}, issn = {1468-4357}, doi = {10.1093/biostatistics/kxs055}, author = {Eloyan, Ani and Crainiceanu, Ciprian M and Caffo, Brian S} } @article {814, title = {Longitudinal scalar-on-functions regression with application to tractography data.}, journal = {Biostatistics}, volume = {14}, year = {2013}, month = {2013 Jul}, pages = {447-61}, abstract = {

We propose a class of estimation techniques for scalar-on-function regression where both outcomes and functional predictors may be observed at multiple visits. Our methods are motivated by a longitudinal brain diffusion tensor imaging tractography study. One of the study{\textquoteright}s primary goals is to evaluate the contemporaneous association between human function and brain imaging over time. The complexity of the study requires the development of methods that can simultaneously incorporate: (1) multiple functional (and scalar) regressors; (2) longitudinal outcome and predictor measurements per patient; (3) Gaussian or non-Gaussian outcomes; and (4) missing values within functional predictors. We propose two versions of a new method, longitudinal functional principal components regression (PCR). These methods extend the well-known functional PCR and allow for different effects of subject-specific trends in curves and of visit-specific deviations from that trend. The new methods are compared with existing approaches, and the most promising techniques are used for analyzing the tractography data.

}, keywords = {Anisotropy, Biostatistics, Brain, Diffusion Tensor Imaging, Humans, Linear Models, Models, Statistical, Multiple Sclerosis, Principal Component Analysis, Regression Analysis}, issn = {1468-4357}, doi = {10.1093/biostatistics/kxs051}, author = {Gertheiss, Jan and Goldsmith, Jeff and Crainiceanu, Ciprian and Greven, Sonja} } @article {802, title = {OASIS is Automated Statistical Inference for Segmentation, with applications to multiple sclerosis lesion segmentation in MRI.}, journal = {Neuroimage Clin}, volume = {2}, year = {2013}, month = {2013}, pages = {402-13}, abstract = {

Magnetic resonance imaging (MRI) can be used to detect lesions in the brains of multiple sclerosis (MS) patients and is essential for diagnosing the disease and monitoring its progression. In practice, lesion load is often quantified by either manual or semi-automated segmentation of MRI, which is time-consuming, costly, and associated with large inter- and intra-observer variability. We propose OASIS is Automated Statistical Inference for Segmentation (OASIS), an automated statistical method for segmenting MS lesions in MRI studies. We use logistic regression models incorporating multiple MRI modalities to estimate voxel-level probabilities of lesion presence. Intensity-normalized T1-weighted, T2-weighted, fluid-attenuated inversion recovery and proton density volumes from 131 MRI studies (98 MS subjects, 33 healthy subjects) with manual lesion segmentations were used to train and validate our model. Within this set, OASIS detected lesions with a partial area under the receiver operating characteristic curve for clinically relevant false positive rates of 1\% and below of 0.59\% (95\% CI; [0.50\%, 0.67\%]) at the voxel level. An experienced MS neuroradiologist compared these segmentations to those produced by LesionTOADS, an image segmentation software that provides segmentation of both lesions and normal brain structures. For lesions, OASIS out-performed LesionTOADS in 74\% (95\% CI: [65\%, 82\%]) of cases for the 98 MS subjects. To further validate the method, we applied OASIS to 169 MRI studies acquired at a separate center. The neuroradiologist again compared the OASIS segmentations to those from LesionTOADS. For lesions, OASIS ranked higher than LesionTOADS in 77\% (95\% CI: [71\%, 83\%]) of cases. For a randomly selected subset of 50 of these studies, one additional radiologist and one neurologist also scored the images. Within this set, the neuroradiologist ranked OASIS higher than LesionTOADS in 76\% (95\% CI: [64\%, 88\%]) of cases, the neurologist 66\% (95\% CI: [52\%, 78\%]) and the radiologist 52\% (95\% CI: [38\%, 66\%]). OASIS obtains the estimated probability for each voxel to be part of a lesion by weighting each imaging modality with coefficient weights. These coefficients are explicit, obtained using standard model fitting techniques, and can be reused in other imaging studies. This fully automated method allows sensitive and specific detection of lesion presence and may be rapidly applied to large collections of images.

}, issn = {2213-1582}, doi = {10.1016/j.nicl.2013.03.002}, author = {Sweeney, Elizabeth M and Shinohara, Russell T and Shiee, Navid and Mateen, Farrah J and Chudgar, Avni A and Cuzzocreo, Jennifer L and Calabresi, Peter A and Pham, Dzung L and Reich, Daniel S and Crainiceanu, Ciprian M} } @article {821, title = {Practical Marginalized Multilevel Models.}, journal = {Stat}, volume = {2}, year = {2013}, month = {2013}, abstract = {

Clustered data analysis is characterized by the need to describe both systematic variation in a mean model and cluster-dependent random variation in an association model. Marginalized multilevel models embrace the robustness and interpretations of a marginal mean model, while retaining the likelihood inference capabilities and flexible dependence structures of a conditional association model. Although there has been increasing recognition of the attractiveness of marginalized multilevel models, there has been a gap in their practical application arising from a lack of readily available estimation procedures. We extend the marginalized multilevel model to allow for nonlinear functions in both the mean and association aspects. We then formulate marginal models through conditional specifications to facilitate estimation with mixed model computational solutions already in place. We illustrate the MMM and approximate MMM approaches on a cerebrovascular deficiency crossover trial using SAS and an epidemiological study on race and visual impairment using R. Datasets, SAS and R code are included as supplemental materials.

}, issn = {0038-9986}, doi = {10.1002/sta4.22}, author = {Griswold, Michael E and Swihart, Bruce J and Caffo, Brian S and Zeger, Scott L} } @article {805, title = {Practical recommendations for population PK studies with sampling time errors.}, journal = {Eur J Clin Pharmacol}, volume = {69}, year = {2013}, month = {2013 Dec}, pages = {2055-64}, abstract = {

PURPOSE: Population pharmacokinetic (PK) data collected from routine clinical practice offers a rich source of valuable information. However, in observational population PK data, accurate time information for blood samples is often missing, resulting in measurement errors (ME) in the sampling time variable. The goal of this study was to investigate the effects on model parameters when a scheduled time is used instead of the actual blood sampling time, and to propose ME correction methods.

METHODS: Simulation studies were conducted based on two major factors: the curvature in PK profiles and the size of ME. As ME correction methods, transform both sides (TBS) models were developed with application of Box-Cox power transformation and Taylor expansion. The TBS models were compared to a conventional population PK model using simulations.

RESULTS: The most important determinant of bias due to time ME was the degree of curvature (nonlinearity) in PK profiles; the smaller the curvature around sampling times, the smaller the associated bias. The second important determinant was the magnitude of ME; the larger the ME, the larger the bias. The proposed TBS models performed better than a conventional population PK modeling when curvature and ME were substantial.

CONCLUSIONS: Time ME in sampling time can lead to bias on the parameter estimators. The following practical recommendations are provided: 1) when the curvature of PK profiles is small, conventional population PK modeling is robust to even large ME; and 2) when the curvature is moderate or large, the proposed methodology reduces bias in parameter estimates.

}, keywords = {Humans, Models, Biological, Pharmacokinetics, Research Design, Time Factors}, issn = {1432-1041}, doi = {10.1007/s00228-013-1576-7}, author = {Choi, Leena and Crainiceanu, Ciprian M and Caffo, Brian S} } @article {801, title = {Quantification of multiple-sclerosis-related brain atrophy in two heterogeneous MRI datasets using mixed-effects modeling.}, journal = {Neuroimage Clin}, volume = {3}, year = {2013}, month = {2013}, pages = {171-9}, abstract = {

Brain atrophy, measured by MRI, has been proposed as a useful surrogate marker for disease progression in multiple sclerosis (MS). However, it is conventionally assumed that the accurate quantification of brain atrophy is made difficult, if not impossible, by changes in the parameters of the MRI acquisition, which are almost inevitable over the course of a longitudinal study since MRI technology changes rapidly. This state of affairs can negatively affect clinical trial design and limit the use of historical data. Here, we investigate whether we can coherently estimate brain atrophy rates in a heterogeneous MS sample via linear mixed-effects multivariable regression, incorporating three critical assumptions: (1) using age at time of scanning, rather than time since baseline, as the regressor of interest; (2) scanning individuals with a variety of techniques; and (3) introducing a simple additive correction for major differences in MRI protocol. We fit the model to several measures of brain volume as the outcome in two MS populations: 1123 scans from 195 cases acquired for over approximately 7~years in two natural history protocols (Cohort 1), and 1331 scans from 69 cases seen for over 11~years who were primarily treated with two specific MS disease-modifying therapies (Cohort 2). We compared the mixed-effects model with additive correction for MRI acquisition parameters to a model fit without this correction and performed sample-size calculations to provide an estimate of the number of participants in an MS clinical trial that might be required to see a therapeutic effect of treatment using the approach described here. The results show that without the additive correction for T1-weighted protocol parameters, atrophy was underestimated and subject-specific estimates were more narrowly distributed about the population mean. Ventricular CSF is the most consistently estimated brain volume, with a mean of 2.8\%/year increase in Cohort 1 and 4.4\%/year increase in Cohort 2. An interesting observation was that gray matter volume decreased and white matter volume remained essentially unchanged in both cohorts, suggesting that changes in ventricular CSF volume are a surrogate for changes in gray matter volume. In conclusion, the mixed-effects modeling framework presented here allows effective use of heterogeneously acquired and historical data in the study of brain atrophy in MS, potentially simplifying the design of future single- and multi-site clinical trials and natural history studies.

}, issn = {2213-1582}, doi = {10.1016/j.nicl.2013.08.001}, author = {Jones, Blake C and Nair, Govind and Shea, Colin D and Crainiceanu, Ciprian M and Cortese, Irene C M and Reich, Daniel S} } @article {803, title = {Quantifying the reliability of image replication studies: the image intraclass correlation coefficient (I2C2).}, journal = {Cogn Affect Behav Neurosci}, volume = {13}, year = {2013}, month = {2013 Dec}, pages = {714-24}, abstract = {

This article proposes the image intraclass correlation (I2C2) coefficient as a global measure of reliability for imaging studies. The I2C2 generalizes the classic intraclass correlation (ICC) coefficient to the case when the data of interest are images, thereby providing a measure that is both intuitive and convenient. Drawing a connection with classical measurement error models for replication experiments, the I2C2 can be computed quickly, even in high-dimensional imaging studies. A nonparametric bootstrap procedure is introduced to quantify the variability of the I2C2 estimator. Furthermore, a Monte Carlo permutation is utilized to test reproducibility versus a zero I2C2, representing complete lack of reproducibility. Methodologies are applied to three replication studies arising from different brain imaging modalities and settings: regional analysis of volumes in normalized space imaging for characterizing brain morphology, seed-voxel brain activation maps based on resting-state functional magnetic resonance imaging (fMRI), and fractional anisotropy in an area surrounding the corpus callosum via diffusion tensor imaging. Notably, resting-state fMRI brain activation maps are found to have low reliability, ranging from .2 to .4. Software and data are available to provide easy access to the proposed methods.

}, keywords = {Adult, Brain, brain mapping, Computer Simulation, Female, Humans, Male, Models, Biological, Neuroimaging, Reproducibility of Results, Statistics as Topic}, issn = {1531-135X}, doi = {10.3758/s13415-013-0196-0}, author = {Shou, H and Eloyan, A and Lee, S and Zipunnikov, V and Crainiceanu, A N and Nebel, N B and Caffo, B and Lindquist, M A and Crainiceanu, C M} } @article {811, title = {Relationships between retinal axonal and neuronal measures and global central nervous system pathology in multiple sclerosis.}, journal = {JAMA Neurol}, volume = {70}, year = {2013}, month = {2013 Jan}, pages = {34-43}, abstract = {

OBJECTIVE: To determine the relationships between conventional and segmentation-derived optical coherence tomography (OCT) retinal layer thickness measures with intracranial volume (a surrogate of head size) and brain substructure volumes in multiple sclerosis (MS).

DESIGN: Cross-sectional study.

SETTING: Johns Hopkins University, Baltimore, Maryland.

PARTICIPANTS: A total of 84 patients with MS and 24 healthy control subjects.

MAIN OUTCOME MEASURES: High-definition spectral-domain OCT conventional and automated segmentation-derived discrete retinal layer thicknesses and 3-T magnetic resonance imaging brain substructure volumes.

RESULTS: Peripapillary retinal nerve fiber layer as well as composite ganglion cell layer+inner plexiform layer thicknesses in the eyes of patients with MS without a history of optic neuritis were associated with cortical gray matter (P=.01 and P=.04, respectively) and caudate (P=.04 and P=.03, respectively) volumes. Inner nuclear layer thickness, also in eyes without a history of optic neuritis, was associated with fluid-attenuated inversion recovery lesion volume (P=.007) and inversely associated with normal-appearing white matter volume (P=.005) in relapsing-remitting MS. As intracranial volume was found to be related with several of the OCT measures in patients with MS and healthy control subjects and is already known to be associated with brain substructure volumes, all OCT-brain substructure relationships were adjusted for intracranial volume. CONCLUSIONS Retinal measures reflect global central nervous system pathology in multiple sclerosis, with thicknesses of discrete retinal layers each appearing to be associated with distinct central nervous system processes. Moreover, OCT measures appear to correlate with intracranial volume in patients with MS and healthy control subjects, an important unexpected factor unaccounted for in prior studies examining the relationships between peripapillary retinal nerve fiber layer thickness and brain substructure volumes.

}, keywords = {Adult, Axons, Caudate Nucleus, Central Nervous System, Cerebral Cortex, Cross-Sectional Studies, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis, Retina, Retinal Neurons, Tomography, Optical Coherence}, issn = {2168-6157}, doi = {10.1001/jamaneurol.2013.573}, author = {Saidha, Shiv and Sotirchos, Elias S and Oh, Jiwon and Syc, Stephanie B and Seigo, Michaela A and Shiee, Navid and Eckstein, Chistopher and Durbin, Mary K and Oakley, Jonathan D and Meyer, Scott A and Frohman, Teresa C and Newsome, Scott and Ratchford, John N and Balcer, Laura J and Pham, Dzung L and Crainiceanu, Ciprian M and Frohman, Elliot M and Reich, Daniel S and Calabresi, Peter A} } @article {827, title = {Analysis of group ICA-based connectivity measures from fMRI: application to Alzheimer{\textquoteright}s disease.}, journal = {PLoS One}, volume = {7}, year = {2012}, month = {2012}, pages = {e49340}, abstract = {

Functional magnetic resonance imaging (fMRI) is a powerful tool for the in vivo study of the pathophysiology of brain disorders and disease. In this manuscript, we propose an analysis stream for fMRI functional connectivity data and apply it to a novel study of Alzheimer{\textquoteright}s disease. In the first stage, spatial independent component analysis is applied to group fMRI data to obtain common brain networks (spatial maps) and subject-specific mixing matrices (time courses). In the second stage, functional principal component analysis is utilized to decompose the mixing matrices into population-level eigenvectors and subject-specific loadings. Inference is performed using permutation-based exact logistic regression for matched pairs data. The method is applied to a novel fMRI study of Alzheimer{\textquoteright}s disease risk under a verbal paired associates task. We found empirical evidence of alternative ICA-based metrics of connectivity when comparing subjects evidencing mild cognitive impairment relative to carefully matched controls.

}, keywords = {Aged, Algorithms, Alzheimer Disease, Brain, brain mapping, Case-Control Studies, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Mild Cognitive Impairment, Nerve Net, Principal Component Analysis, Task Performance and Analysis, Time Factors}, issn = {1932-6203}, doi = {10.1371/journal.pone.0049340}, author = {Li, Shanshan and Eloyan, Ani and Joel, Suresh and Mostofsky, Stewart and Pekar, James and Bassett, Susan Spear and Caffo, Brian} } @article {685, title = {Analysis of tiling array expression studies with flexible designs in Bioconductor (waveTiling.}, journal = {BMC Bioinformatics}, volume = {13}, year = {2012}, month = {2012 Sep 14}, pages = {234}, abstract = {

ABSTRACT: BACKGROUND: Existing statistical methods for tiling array transcriptome data either focus on transcript discovery in one biological or experimental condition or on the detection of differential expression between two conditions. Increasingly often, however, biologists are interested in time-course studies, studies with more than two conditions or even multiple-factor studies. As these studies are currently analyzed with the traditional microarray analysis techniques, they do not exploit the genome-wide nature of tiling array data to its full potential. RESULTS: We present an R Bioconductor package, waveTiling, which implements a wavelet-based model for analyzing transcriptome data and extends it towards more complex experimental designs. With waveTiling the user is able to discover (1) group-wise expressed regions, (2) differentially expressed regions between any two groups in single-factor studies and in (3) multifactorial designs. Moreover, for time-course experiments it is also possible to detect (4) linear time effects and (5) a circadian rhythm of transcripts. By considering the expression values of the individual tiling probes as a function of genomic position, effect regions can be detected regardless of existing annotation. Three case studies with different experimental set-ups illustrate the use and the flexibility of the model-based transcriptome analysis. CONCLUSIONS: The waveTiling package provides the user with a convenient tool for the analysis of tiling array trancriptome data for a multitude of experimental set-ups. Regardless of the study design, the probe-wise analysis allows for the detection of transcriptional effects in both exonic, intronic and intergenic regions, without prior consultation of existing annotation.

}, issn = {1471-2105}, doi = {10.1186/1471-2105-13-234}, author = {De Beuf, K. and Pipelers, Peter and Andriankaja, Megan and Thas, O. and Inz{\'e}, Dirk and Crainiceanu, C and Clement, Lieven} } @article {708, title = {Arsenic exposure, diabetes prevalence, and diabetes control in the Strong Heart Study.}, journal = {Am J Epidemiol}, volume = {176}, year = {2012}, month = {2012 Nov 15}, pages = {865-74}, abstract = {

This study evaluated the association of arsenic exposure, as measured in urine, with diabetes prevalence, glycated hemoglobin, and insulin resistance in American Indian adults from Arizona, Oklahoma, and North and South Dakota (1989-1991). We studied 3,925 men and women 45-74 years of age with available urine arsenic measures. Diabetes was defined as a fasting glucose level of 126 mg/dL or higher, a 2-hour glucose level of 200 mg/dL or higher, a hemoglobin A1c (HbA1c) of 6.5\% or higher, or diabetes treatment. Median urine arsenic concentration was 14.1 {\textmu}g/L (interquartile range, 7.9-24.2). Diabetes prevalence was 49.4\%. After adjustment for sociodemographic factors, diabetes risk factors, and urine creatinine, the prevalence ratio of diabetes comparing the 75th versus 25th percentiles of total arsenic concentrations was 1.14 (95\% confidence interval: 1.08, 1.21). The association between arsenic and diabetes was restricted to participants with poor diabetes control (HbA1c >=8\%). Arsenic was positively associated with HbA1c levels in participants with diabetes. Arsenic was not associated with HbA1c or with insulin resistance (assessed by homeostatic model assessment to quantify insulin resistance) in participants without diabetes. Urine arsenic was associated with diabetes control in a population from rural communities in the United States with a high burden of diabetes. Prospective studies that evaluate the direction of the relation between poor diabetes control and arsenic exposure are needed.

}, keywords = {Aged, Arizona, Arsenicals, Blood Glucose, Creatinine, Diabetes Mellitus, Environmental Exposure, Female, Hemoglobin A, Glycosylated, Humans, Indians, North American, Male, Middle Aged, North Dakota, Oklahoma, Poisson Distribution, Prevalence, Regression Analysis, Risk Factors, South Dakota}, issn = {1476-6256}, doi = {10.1093/aje/kws153}, author = {Gribble, Matthew O and Howard, Barbara V and Umans, Jason G and Shara, Nawar M and Francesconi, Kevin A and Goessler, Walter and Crainiceanu, Ciprian M and Silbergeld, Ellen K and Guallar, Eliseo and Navas-Acien, Ana} } @article {calSimex, title = {Assessment of bias in experimentally measured diffusion tensor imaging parameters using SIMEX}, journal = {Accepted in Magnetic Resonance in Medicine}, year = {2012}, author = {Lauzon, C and Crainiceanu, C and Caffo, B and Landman, B} } @article {621, title = {Automatic Lesion Incidence Estimation and Detection in Multiple Sclerosis Using Multisequence Longitudinal MRI.}, journal = {AJNR Am J Neuroradiol}, year = {2012}, month = {2012 Jul 5}, abstract = {

BACKGROUND AND PURPOSE:Detecting incidence and enlargement of lesions is essential in monitoring the progression of MS. In clinical trials, lesion load is observed by manually segmenting and comparing serial MR images, which is time consuming, costly, and prone to inter- and intraobserver variability. Subtracting images from consecutive time points nulls stable lesions, leaving only new lesion activity. We propose SuBLIME, an automated method for segmenting incident lesion voxels.MATERIALS AND METHODS:We used logistic regression models incorporating multiple MR imaging sequences and subtraction images from consecutive longitudinal studies to estimate voxel-level probabilities of lesion incidence. We used T1-weighted, T2-weighted, FLAIR, and PD volumes from a total of 110 MR imaging studies from 10 subjects.RESULTS:To assess the performance of the model, we assigned 5 subjects to a training set and the remaining 5 to a validation set. With SuBLIME, lesion incidence is detected and delineated in the validation set with an AUC of 99\% (95\% CI [97\%, 100\%]) at the voxel level.CONCLUSIONS:This fully automated and computationally fast method allows sensitive and specific detection of lesion incidence that can be applied to large collections of images. Using the explicit form of the statistical model, SuBLIME can easily be adapted to cases when more or fewer imaging sequences are available.

}, issn = {1936-959X}, doi = {10.3174/ajnr.A3172}, author = {Sweeney, E M and Shinohara, R and Shea, C D and Reich, D S and Crainiceanu, C} } @article {landmanb, title = {Biological parametric mapping accounting for random regressors with regression calibration and model II regression}, journal = {Accepted in Neuroimage}, year = {2012}, author = {Yang, X and Lauzon, C and Crainiceanu, C and Caffo, B and Resnick, S and Landman, B} } @article {679, title = {Bootstrap-based inference on the difference in the means of two correlated functional processes.}, journal = {Stat Med}, year = {2012}, month = {2012 Aug 1}, abstract = {

We propose nonparametric inference methods on the mean difference between two correlated functional processes. We compare methods that (1) incorporate different levels of smoothing of the mean and covariance; (2) preserve the sampling design; and (3) use parametric and nonparametric estimation of the mean functions. We apply our method to estimating the mean difference between average normalized δ power of sleep electroencephalograms for 51 subjects with severe sleep apnea and 51 matched controls in the first 4\ ;h after sleep onset. We obtain data from the Sleep Heart Health Study, the largest community cohort study of sleep. Although methods are applied to a single case study, they can be applied to a large number of studies that have correlated functional data. Copyright {\textcopyright} 2012 John Wiley \& Sons, Ltd.

}, issn = {1097-0258}, doi = {10.1002/sim.5439}, author = {Crainiceanu, C and Staicu, A. M. and Ray, Shubankar and Punjabi, Naresh} } @article {pmid22472185, title = {Cadmium Exposure and All Cause and Cardiovascular Mortality in the US General Population}, journal = {Environ Health Perspect}, year = {2012}, month = {Apr}, author = {Tellez-Plaza, M. and Navas-Acien, A. and Menke, A. and Crainiceanu, C and Pastor-Barriuso, R. and Guallar, E.} } @article {thom, title = {Comparison of swab versus sponge methodology for the identification of acinetobacter baumannii from the hospital environment}, journal = {Accepted in the Journal of Clinical Microbiology}, year = {2012}, author = {Thom, K and Howard, T and Sembajwe, S and Harris, A and Strassle, P and Caffo, B and Caroll, K and Johnson, J} } @article {ellignton, title = {Computerized lung sound analysis to improve the specificity of pediatric pneumonia in resource-poor settings}, journal = {Accepted in the British Medical Journal Open}, year = {2012}, author = {Ellington, L and Gilman, R and Tielsch, J and Steinhoff, M and Figueroa, D and Rodriguez, S and Caffo, B and Tracey, B and West, J and Checkley, W} } @article {cstechn2012, title = {Discussion of {\textquoteleft}Clustering random curves under spatial interdependence with application to service accessibility{\textquoteright}}, journal = {Technometrics}, year = {2012}, pages = {to appear}, author = {Crainiceanu, C and Staicu, A. M.} } @article {nicole, title = {Distribution of cell-free and cell-associated HIV surrogates in the female genital tract following simulated vaginal intercourse}, journal = {Appeared online in the Journal of Infectious Diseases}, year = {2012}, author = {Louissaint, N and Nimmagadda, S and Bakshi, R and Du, Y and Macura, K and King, K and Wahl, R and Goldsmith, J and Caffo, B and Cao, Y and Anderson, J and Fuchs, E and Hendrix, C} } @article {cribben2012dynamic, title = {Dynamic connectivity regression: Determining state-related changes in brain connectivity}, journal = {NeuroImage}, year = {2012}, publisher = {Elsevier}, author = {Cribben, Ivor and Haraldsdottir, Ragnheidur and Atlas, Lauren Y and Wager, Tor D and Lindquist, Martin A} } @article {842, title = {Dynamic connectivity regression: determining state-related changes in brain connectivity.}, journal = {Neuroimage}, volume = {61}, year = {2012}, month = {2012 Jul 16}, pages = {907-20}, abstract = {

Most statistical analyses of fMRI data assume that the nature, timing and duration of the psychological processes being studied are known. However, often it is hard to specify this information a priori. In this work we introduce a data-driven technique for partitioning the experimental time course into distinct temporal intervals with different multivariate functional connectivity patterns between a set of regions of interest (ROIs). The technique, called Dynamic Connectivity Regression (DCR), detects temporal change points in functional connectivity and estimates a graph, or set of relationships between ROIs, for data in the temporal partition that falls between pairs of change points. Hence, DCR allows for estimation of both the time of change in connectivity and the connectivity graph for each partition, without requiring prior knowledge of the nature of the experimental design. Permutation and bootstrapping methods are used to perform inference on the change points. The method is applied to various simulated data sets as well as to an fMRI data set from a study (N=26) of a state anxiety induction using a socially evaluative threat challenge. The results illustrate the method{\textquoteright}s ability to observe how the networks between different brain regions changed with subjects{\textquoteright} emotional state.

}, keywords = {Algorithms, Brain, brain mapping, Computer Simulation, Emotions, Humans, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Neural Pathways}, issn = {1095-9572}, doi = {10.1016/j.neuroimage.2012.03.070}, author = {Cribben, Ivor and Haraldsdottir, Ragnheidur and Atlas, Lauren Y and Wager, Tor D and Lindquist, Martin A} } @article {pmid22221585, title = {Effect of correcting for long-term variation in major coronary heart disease risk factors: relative hazard estimation and risk prediction in the Atherosclerosis Risk in Communities Study}, journal = {Ann Epidemiol}, volume = {22}, number = {3}, year = {2012}, month = {Mar}, pages = {191{\textendash}197}, author = {Paynter, N. P. and Crainiceanu, C and Sharrett, A. R. and Chambless, L. E. and Coresh, J.} } @article {pmid22499683, title = {Fast wavelet based functional models for transcriptome analysis with tiling arrays}, journal = {Stat Appl Genet Mol Biol}, volume = {11}, number = {1}, year = {2012}, pages = {1{\textendash}36}, author = {Clement, Lieven and De Beuf, K. and Thas, O. and Vuylsteke, M. and Irizarry, R and Crainiceanu, C} } @article {james, title = {Genetic risk factors for longitudinal changes in structural MRI in former organolead workers}, journal = {Accepted in the Journal of Aging Research}, year = {2012}, author = {James, B and Caffo, B and Stewart, W and Yousem, D and Davatzikos, C. and Schwartz, B} } @article {goldsmith, title = {Longitudinal penalized functional regression for cognitive outcomes on neuronal tract measurements}, journal = {Journal of the Royal Statistical Society Series C}, number = {61}, year = {2012}, pages = {453{\textendash}469}, author = {Goldsmith, J and Crainiceanu, C and Caffo, B and Reich, D.} } @article {709, title = {Microcystic macular oedema, thickness of the inner nuclear layer of the retina, and disease characteristics in multiple sclerosis: a retrospective study.}, journal = {Lancet Neurol}, volume = {11}, year = {2012}, month = {2012 Nov}, pages = {963-72}, abstract = {

BACKGROUND: Microcystic macular oedema (MMO) of the retinal inner nuclear layer (INL) has been identified in patients with multiple sclerosis (MS) by use of optical coherence tomography (OCT). We aimed to determine whether MMO of the INL, and increased thickness of the INL are associated with disease activity or disability progression.

METHODS: This retrospective study was done at the Johns Hopkins Hospital (Baltimore, MD, USA), between September, 2008, and March, 2012. Patients with MS and healthy controls underwent serial OCT scans and clinical assessments including visual function. OCT scanning, including automated intraretinal layer segmentation, yielded thicknesses of the retinal nerve fibre layer, the ganglion cell layer plus inner plexiform layer, the INL plus outer plexiform layer (the combined thickness of these layers was used as a surrogate measure of INL thickness), and the outer nuclear layer. Patients with MS also underwent annual brain MRI scans. Disability scores were compared with the Wilcoxon rank-sum test. Mixed-effects linear regression was used to compare OCT measures and letter-acuity scores. Logistic regression was used to examine the relations of baseline OCT thicknesses with clinical and radiological parameters.

FINDINGS: 164 patients with MS and 60 healthy controls were assessed. Mean follow-up was 25{\textperiodcentered}8 months (SD 9{\textperiodcentered}1) for patients with MS and 22{\textperiodcentered}4 months (11{\textperiodcentered}4) for healthy controls. Ten (6\%) patients with MS had MMO during at least one study visit; MMO was visible at baseline in four of these patients. Healthy controls did not have MMO. Patients with MS and MMO had higher baseline MS severity scores (median 5{\textperiodcentered}93 [range 2{\textperiodcentered}44-8{\textperiodcentered}91]) than those who did not have MMO at any time during the study (151 patients; 3{\textperiodcentered}81 [0{\textperiodcentered}13-9{\textperiodcentered}47]; p=0{\textperiodcentered}032), although expanded disability status scale (EDSS) scores were not significantly different (5{\textperiodcentered}2 [1{\textperiodcentered}0-6{\textperiodcentered}5] for patients with MS and MMO vs 2{\textperiodcentered}5 [0{\textperiodcentered}0-8{\textperiodcentered}0] for those without MMO; p=0{\textperiodcentered}097). The eyes of patients with MS and MMO (12 eyes) versus those without MMO (302 eyes) had lower letter-acuity scores (100\% contrast, p=0{\textperiodcentered}017; 2{\textperiodcentered}5\% contrast, p=0{\textperiodcentered}031; 1{\textperiodcentered}25\% contrast, p=0{\textperiodcentered}014), and increased INL thicknesses (p=0{\textperiodcentered}003) at baseline. Increased baseline INL thickness in patients with MS was associated with the development of contrast-enhancing lesions (p=0{\textperiodcentered}007), new T2 lesions (p=0{\textperiodcentered}015), EDSS progression (p=0{\textperiodcentered}034), and relapses in patients with relapsing-remitting MS (p=0{\textperiodcentered}008) during the study. MMO was not associated with disease activity during follow-up.

INTERPRETATION: Increased INL thickness on OCT is associated with disease activity in MS. If this finding is confirmed, INL thickness could be a useful predictor of disease progression in patients with MS.

FUNDING: National Multiple Sclerosis Society, National Eye Institute, Braxton Debbie Angela Dillon and Skip Donor Advisor Fund.

}, keywords = {Adult, Cohort Studies, Female, Follow-Up Studies, Humans, Macular Edema, Male, Middle Aged, Multiple Sclerosis, Retina, Retinal Ganglion Cells, Retrospective Studies, Tomography, Optical Coherence}, issn = {1474-4465}, doi = {10.1016/S1474-4422(12)70213-2}, author = {Saidha, Shiv and Sotirchos, Elias S and Ibrahim, Mohamed A and Crainiceanu, Ciprian M and Gelfand, Jeffrey M and Sepah, Yasir J and Ratchford, John N and Oh, Jiwon and Seigo, Michaela A and Newsome, Scott D and Balcer, Laura J and Frohman, Elliot M and Green, Ari J and Nguyen, Quan D and Calabresi, Peter A} } @article {pmid22241689, title = {Mixed effect Poisson log-linear models for clinical and epidemiological sleep hypnogram data}, journal = {Stat Med}, volume = {31}, number = {9}, year = {2012}, month = {Apr}, pages = {855{\textendash}870}, author = {Swihart, B and Caffo, B and Crainiceanu, C and Punjabi, N.M.} } @article {swihartTransition, title = {Models of sleep hypnograms scalable to epidemiological studies}, journal = {Tentatively accepted in Statistics in Medicine}, year = {2012}, author = {Swihart, B and Caffo, B and Crainiceanu, C and Punjabi, N} } @article {barber, title = {Motor "dexterity"?: evidence that left hemisphere lateralization of motor circuit connectivity is associated with better motor performance in children}, journal = {Cerebral Cortex}, year = {2012}, author = {Barber, A and Srinivasan, P and Joel, S. and Caffo, B and Pekar, J and Mostofsky, S} } @article {BaGoCaGlCr2012, title = {Movelets: A dictionary of movement}, journal = {Electronic Journal of Statistics}, volume = {6}, year = {2012}, pages = {559-578}, issn = {1935-7524}, doi = {10.1214/12-EJS684}, author = {Bai, J and Goldsmith, J and Caffo, B and Glass, T and Crainiceanu, C} } @article {813, title = {Movelets: A dictionary of movement.}, journal = {Electron J Stat}, volume = {6}, year = {2012}, month = {2012}, pages = {559-578}, abstract = {

Recent technological advances provide researchers with a way of gathering real-time information on an individual{\textquoteright}s movement through the use of wearable devices that record acceleration. In this paper, we propose a method for identifying activity types, like walking, standing, and resting, from acceleration data. Our approach decomposes movements into short components called "movelets", and builds a reference for each activity type. Unknown activities are predicted by matching new movelets to the reference. We apply our method to data collected from a single, three-axis accelerometer and focus on activities of interest in studying physical function in elderly populations. An important technical advantage of our methods is that they allow identification of short activities, such as taking two or three steps and then stopping, as well as low frequency rare(compared with the whole time series) activities, such as sitting on a chair. Based on our results we provide simple and actionable recommendations for the design and implementation of large epidemiological studies that could collect accelerometry data for the purpose of predicting the time series of activities and connecting it to health outcomes.

}, issn = {1935-7524}, doi = {10.1214/12-EJS684}, author = {Bai, Jiawei and Goldsmith, Jeff and Caffo, Brian and Glass, Thomas A and Crainiceanu, Ciprian M} } @article {pmid22006982, title = {Optical coherence tomography segmentation reveals ganglion cell layer pathology after optic neuritis}, journal = {Brain}, volume = {135}, number = {Pt 2}, year = {2012}, month = {Feb}, pages = {521{\textendash}533}, author = {Syc, S. B. and Saidha, S. and Newsome, S and Ratchford, J and Levy, M. and Ford, E. and Crainiceanu, C and Durbin, M. K. and Oakley, J. D. and Meyer, S. A. and Frohman, E. M. and Calabresi, P} } @article {goldsmithNI, title = {Penalized functional regression analysis of white-matter tract profiles in multiple sclerosis}, journal = {Accepted in Neuroimage, PMCID: PMC3114268}, year = {2012}, author = {Goldsmith, J and Crainiceanu, C and Caffo, B and Reich, D.} } @article {pmid22442041, title = {Predicting Breakdown of the Blood-Brain Barrier in Multiple Sclerosis without Contrast Agents}, journal = {AJNR Am J Neuroradiol}, year = {2012}, month = {Mar}, author = {Shinohara, R and Goldsmith, J and Mateen, F J and Crainiceanu, C and Reich, D S} } @article {rectalab, title = {Quantification of the spatial distribution of rectally-applied surrogates for microbicide and semen in colon with SPECT imaging}, journal = {Accepted in the British Journal of Clinical Pharmacology}, year = {2012}, author = {Cao, Y and Caffo, B and Fuchs, E and Lee, L and Du, Y and Li, L and Bakshi, R and Khan, W and Wahl, R and Grohskopf, L and Hendrix, C} } @article {710, title = {Relationships Between Retinal Axonal and Neuronal Measures and Global Central Nervous System Pathology in Multiple Sclerosis.}, journal = {Arch Neurol}, year = {2012}, month = {2012 Oct 1}, pages = {1-10}, abstract = {

OBJECTIVE To determine the relationships between conventional and segmentation-derived optical coherence tomography (OCT) retinal layer thickness measures with intracranial volume (a surrogate of head size) and brain substructure volumes in multiple sclerosis (MS). DESIGN Cross-sectional study. SETTING Johns Hopkins University, Baltimore, Maryland. PARTICIPANTS A total of 84 patients with MS and 24 healthy control subjects. MAIN OUTCOME MEASURES High-definition spectral-domain OCT conventional and automated segmentation-derived discrete retinal layer thicknesses and 3-T magnetic resonance imaging brain substructure volumes. RESULTS Peripapillary retinal nerve fiber layer as well as composite ganglion cell layer\ +\ inner plexiform layer thicknesses in the eyes of patients with MS without a history of optic neuritis were associated with cortical gray matter (P\ =\ .01 and P\ =\ .04, respectively) and caudate (P\ =\ .04 and P\ =\ .03, respectively) volumes. Inner nuclear layer thickness, also in eyes without a history of optic neuritis, was associated with fluid-attenuated inversion recovery lesion volume (P\ =\ .007) and inversely associated with normal-appearing white matter volume (P\ =\ .005) in relapsing-remitting MS. As intracranial volume was found to be related with several of the OCT measures in patients with MS and healthy control subjects and is already known to be associated with brain substructure volumes, all OCT-brain substructure relationships were adjusted for intracranial volume. CONCLUSIONS Retinal measures reflect global central nervous system pathology in multiple sclerosis, with thicknesses of discrete retinal layers each appearing to be associated with distinct central nervous system processes. Moreover, OCT measures appear to correlate with intracranial volume in patients with MS and healthy control subjects, an important unexpected factor unaccounted for in prior studies examining the relationships between peripapillary retinal nerve fiber layer thickness and brain substructure volumes.

}, issn = {1538-3687}, doi = {10.1001/archneurol.2013.573}, author = {Saidha, Shiv and Sotirchos, Elias S and Oh, Jiwon and Syc, Stephanie B and Seigo, Michaela A and Shiee, Navid and Eckstein, Chistopher and Durbin, Mary K and Oakley, Jonathan D and Meyer, Scott A and Frohman, Teresa C and Newsome, Scott and Ratchford, John N and Balcer, Laura J and Pham, Dzung L and Crainiceanu, Ciprian M and Frohman, Elliot M and Reich, Daniel S and Calabresi, Peter A} } @article {shee, title = {Revisiting Brain Atrophy and Its Relationship to Disability in Multiple Sclerosis}, journal = {PLoS ONE}, volume = {7}, number = {5}, year = {2012}, month = {05}, pages = {e37049}, publisher = {Public Library of Science}, doi = {10.1371/journal.pone.0037049}, url = {http://dx.doi.org/10.1371\%2Fjournal.pone.0037049}, author = {Shiee, N and Bazin, P and Zackowski, K and Farrell, S and Harrison, D and Newsome, S and Ratchford, J and Caffo, B and Calabresi, P and Pham, D and Reich, D.} } @article {nareshCaffeine, title = {Sleep-Disordered breathing and caffeine consumption: results of a community-based study}, journal = {Accepted in Chest}, year = {2012}, author = {Aurora, RN and Crainiceanu, C and Caffo, B and Punjabi, N} } @article {830, title = {Total white matter hyperintensity volume in bipolar disorder patients and their healthy relatives.}, journal = {Bipolar Disord}, volume = {14}, year = {2012}, month = {2012 Dec}, pages = {888-93}, abstract = {

OBJECTIVES: White matter hyperintensities (WMH) are more common in subjects with bipolar disorder (BP) than in healthy subjects (HS). Few studies have examined the effect of the diagnostic type of bipolar illness on WMH burden, and none have approached this question through a direct measurement of the volume of affected white matter in relationship to familiality. In this pilot study, we utilized a volumetric measurement of WMH to investigate the relationship between the total volume of WMH and the familiality and type of BP.

METHODS: Forty-five individuals with bipolar I disorder (BP-I) with psychotic features, BP-I without psychotic features, or bipolar II disorder (BP-II), seven of their unaffected relatives, and 32 HS were recruited for participation. T-2 weighted magnetic resonance imaging scans were obtained on all subjects, and the total volume of all WMH for each subject was measured in cubic centimeters. The significance of difference between groups was tested using ANOVA with post-hoc adjustment for multiple comparisons. Further, we used logistic regression to test for trends between symptom load and total WMH volume.

RESULTS: The mean total volume of WMH in BP-I patients with psychotic features was significantly higher (p < 0.05) than that of HS. Further, we observed a positive linear trend by familiality and type of affectedness when comparing mean total WMH volume of HS, unaffected family members, subjects with BP-II, and BP-I with and without a history of psychosis (p < 0.05).

CONCLUSIONS: Based on a quantitative technique, WMH burden appears to be associated with familiality and type of BP. The significance of these findings remains to be fully elucidated.

}, keywords = {Adult, Analysis of Variance, Bipolar Disorder, Brain, Female, Humans, Image Processing, Computer-Assisted, Leukoencephalopathies, Magnetic Resonance Imaging, Male, Nerve Fibers, Myelinated}, issn = {1399-5618}, doi = {10.1111/bdi.12019}, author = {Tighe, Sarah K and Reading, Sarah A and Rivkin, Paul and Caffo, Brian and Schweizer, Barbara and Pearlson, Godfrey and Potash, James B and Depaulo, J Raymond and Bassett, Susan S} } @article {832, title = {Towards Automatic Quantitative Quality Control for MRI.}, journal = {Proc Soc Photo Opt Instrum Eng}, volume = {8314}, year = {2012}, month = {2012 Feb 23}, abstract = {

Quality and consistency of clinical and research data collected from Magnetic Resonance Imaging (MRI) scanners may become suspect due to a wide variety of common factors including, experimental changes, hardware degradation, hardware replacement, software updates, personnel changes, and observed imaging artifacts. Standard practice limits quality analysis to visual assessment by a researcher/clinician or a quantitative quality control based upon phantoms which may not be timely, cannot account for differing experimental protocol (e.g. gradient timings and strengths), and may not be pertinent to the data or experimental question at hand. This paper presents a parallel processing pipeline developed towards experiment specific automatic quantitative quality control of MRI data using diffusion tensor imaging (DTI) as an experimental test case. The pipeline consists of automatic identification of DTI scans run on the MRI scanner, calculation of DTI contrasts from the data, implementation of modern statistical methods (wild bootstrap and SIMEX) to assess variance and bias in DTI contrasts, and quality assessment via power calculations and normative values. For this pipeline, a DTI specific power calculation analysis is developed as well as the first incorporation of bias estimates in DTI data to improve statistical analysis.

}, issn = {1018-4732}, doi = {10.1117/12.910819}, author = {Lauzon, Carolyn B and Caffo, Brian C and Landman, Bennett A} } @article {ANA:ANA22452, title = {Assessing bioequivalence of generic antiepilepsy drugs}, journal = {Annals of Neurology, NIHMSID: 286919}, volume = {70}, number = {2}, year = {2011}, pages = {221{\textendash}228}, publisher = {Wiley Subscription Services, Inc., A Wiley Company}, issn = {1531-8249}, doi = {10.1002/ana.22452}, url = {http://dx.doi.org/10.1002/ana.22452}, author = {Krauss, G and Caffo, B and Chang, Y and Hendrix, C and Chuang, K} } @article {pmid21995019, title = {Assessment of bias for MRI diffusion tensor imaging using SIMEX}, journal = {Med Image Comput Comput Assist Interv}, volume = {14}, number = {Pt 2}, year = {2011}, pages = {107{\textendash}115}, author = {Lauzon, C and Asman, A. J. and Crainiceanu, C and Caffo, B and Landman, B} } @article {springerlink:10.1007/s10928-011-9211-7, title = {A Bayesian hierarchical nonlinear mixture model in the presence of artifactual outliers in a population pharmacokinetic study}, journal = {Journal of Pharmacokinetics and Pharmacodynamics}, volume = {38}, year = {2011}, note = {10.1007/s10928-011-9211-7}, pages = {613-636}, publisher = {Springer Netherlands}, issn = {1567-567X}, url = {http://dx.doi.org/10.1007/s10928-011-9211-7}, author = {Choi, L and Caffo, B and Kohli, U and Pandharipande, P and Kurnik, D and Ely, E and Stein, C} } @article {PACE:PACE2905, title = {Clinical predictors of conduction disease progression in type I myotonic muscular dystrophy}, journal = {Pacing and Clinical Electrophysiology, PMCID: PMC3035751}, volume = {34}, number = {2}, year = {2011}, pages = {171{\textendash}176}, publisher = {Blackwell Publishing Inc}, keywords = {cardiomyopathy, conduction disease, electrocardiography, myotonic muscular dystrophy, sudden death}, issn = {1540-8159}, doi = {10.1111/j.1540-8159.2010.02905.x}, url = {http://dx.doi.org/10.1111/j.1540-8159.2010.02905.x}, author = {Nazarian, S and Wagner, K and Caffo, B and Tomaselli, G} } @article {li3, title = {Comparison of proportions for composite endpoints with missing components}, journal = {Journal of Biopharmaceutical Statistics, NIHMSID: 316386}, volume = {21}, year = {2011}, pages = {271{\textendash}281}, author = {Li, X and Caffo, B} } @article {aurora2011correlating, title = {Correlating subjective and objective sleepiness: revisiting the association using survival analysis.}, journal = {Sleep}, volume = {34}, number = {12}, year = {2011}, pages = {1707}, author = {Aurora, RN and Caffo, B and Crainiceanu, C and Punjabi, N} } @article {nicole2, title = {Distribution of Cell-free and Cell-associated HIV surrogates in the Colon Following Simulated Receptive Anal Intercourse in Healthy Men}, journal = {Journal of Acquired Immune Defficiency Syndromes, Basic and Translational Science}, volume = {59}, number = {1}, year = {2011}, pages = {10{\textendash}17}, author = {Louissaint, N and Nimmagadda, S and Fuchs, E and Bashki, R and Cao, Y and Lee, L and Goldsmith, J and Caffo, B and Du, Y and King, K and Menendez, F and Torbenson, M and Hendrix, C} } @article {622, title = {Dynamics of large-scale cortical interactions at high gamma frequencies during word production: event related causality (ERC) analysis of human electrocorticography (ECoG).}, journal = {Neuroimage}, volume = {56}, year = {2011}, month = {2011 Jun 15}, pages = {2218-37}, abstract = {

Intracranial EEG studies in humans have shown that functional brain activation in a variety of functional-anatomic domains of human cortex is associated with an increase in power at a broad range of high gamma (\>60Hz) frequencies. Although these electrophysiological responses are highly specific for the location and timing of cortical processing and in animal recordings are highly correlated with increased population firing rates, there has been little direct empirical evidence for causal interactions between different recording sites at high gamma frequencies. Such causal interactions are hypothesized to occur during cognitive tasks that activate multiple brain regions. To determine whether such causal interactions occur at high gamma frequencies and to investigate their functional significance, we used event-related causality (ERC) analysis to estimate the dynamics, directionality, and magnitude of event-related causal interactions using subdural electrocorticography (ECoG) recorded during two word production tasks: picture naming and auditory word repetition. A clinical subject who had normal hearing but was skilled in American Signed Language (ASL) provided a unique opportunity to test our hypothesis with reference to a predictable pattern of causal interactions, i.e. that language cortex interacts with different areas of sensorimotor cortex during spoken vs. signed responses. Our ERC analyses confirmed this prediction. During word production with spoken responses, perisylvian language sites had prominent causal interactions with mouth/tongue areas of motor cortex, and when responses were gestured in sign language, the most prominent interactions involved hand and arm areas of motor cortex. Furthermore, we found that the sites from which the most numerous and prominent causal interactions originated, i.e. sites with a pattern of ERC "divergence", were also sites where high gamma power increases were most prominent and where electrocortical stimulation mapping interfered with word production. These findings suggest that the number, strength and directionality of event-related causal interactions may help identify network nodes that are not only activated by a task but are critical to its performance.

}, keywords = {brain mapping, Cerebral Cortex, Electroencephalography, Female, Humans, Middle Aged, Neural Pathways, Seizures, Signal Processing, Computer-Assisted, Speech}, issn = {1095-9572}, doi = {10.1016/j.neuroimage.2011.03.030}, author = {Korzeniewska, A. and Franaszczuk, Piotr J. and Crainiceanu, C and Ku{\'s}, Rafa{\l} and Crone, Nathan E.} } @article {reiss2011extracting, title = {Extracting information from functional connectivity maps via function-on-scalar regression}, journal = {NeuroImage}, volume = {56}, number = {1}, year = {2011}, pages = {140{\textendash}148}, author = {Reiss, P.T. and Mennes, M. and Petkova, E. and Huang, L. and Hoptman, M.J. and Biswal, B.B. and Colcombe, S.J. and Zuo, X.N. and Milham, M.P.} } @article {VP11_QAP, title = {Fast Inexact Graph Mathing with Applications in Statistical Connectomics}, journal = {under review}, year = {2011}, author = {Vogelstein, Joshua T and Conroy, John C and Podrazik, Louis J and Kratzer, Steven G and Fishkind, Donniell E and Vogelstein, Joshua T and Priebe, Carey E} } @article {vadimNI, title = {Functional principal components model for high-dimensional brain imaging}, journal = {Neuroimage, NIHSMID: 316403}, volume = {58}, number = {3}, year = {2011}, pages = {772 {\textendash} 784}, author = {Zipunnikov, V. and Caffo, B and Yousem, D and Davatziko, C and Schwartz, B and Crainiceanu, C} } @article {Gold:Wand:Crai:func:2011, title = {Functional Regression Via Variational Bayes}, journal = {Electronic Journal of Statistics}, volume = {5}, year = {2011}, pages = {572{\textendash}602}, keywords = {approximate Bayesian inference, Markov chain Monte Carlo, penalized splines}, author = {Goldsmith, J and Wand, Matt P. and Crainiceanu, C} } @article {pmid21853058, title = {The impact of utilizing different optical coherence tomography devices for clinical purposes and in multiple sclerosis trials}, journal = {PLoS ONE}, volume = {6}, number = {8}, year = {2011}, pages = {e22947}, author = {Warner, C. V. and Syc, S. B. and Stankiewicz, A. M. and Hiremath, G. and Farrell, S and Crainiceanu, C and Conger, A. and Frohman, T. C. and Bisker, E. R. and Balcer, L and Frohman, E. 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title = {Differential brain activation in anorexia nervosa to Fat and Thin words during a Stroop task}, journal = {NeuroReport, PMCID: PMC2891098}, volume = {19}, number = {12}, year = {2008}, pages = {1181{\textendash}1185}, author = {Redgrave, G and Bakker, A and Bello, N and Caffo, B and Coughlin, J and Guarda, A and McEntee, J and Pekar, J and Reinblatt, S and Verduzco, G. and Moran, T} } @article {Korz:Crai:Ku:Fran:Cron:dyna:2008, title = {Dynamics of Event-related Causality in Brain Electrical Activity}, journal = {Human Brain Mapping}, volume = {29}, number = {10}, year = {2008}, pages = {1170{\textendash}1192}, keywords = {brain mapping, cortical synchronization, EEG, Language, Multivariate analysis, Neural network, neural transmission, Signal processing}, author = {Korzeniewska, A. and Crainiceanu, C and Ku{\'s}, Rafa{\l}{} and Franaszczuk, Piotr J. and Crone, Nathan E.} } @article {guilarte2008dysregulation, title = {Dysregulation of Glutamate Carboxypeptidase II in Psychiatric Disease}, journal = {Schizophrenia Research, PMCID: PMC2287371}, volume = {99}, number = {1-3}, year = {2008}, pages = {324{\textendash}332}, publisher = {NIH Public Access}, author = {Guilarte, T and Hammoud, D and McGlothan, J and Caffo, B and Foss, C and Kozikowski, A and Pomper, M} } @article {Kriv:Crai:Kaue:fast:2008, title = {Fast Adaptive Penalized Splines}, journal = {Journal of Computational and Graphical Statistics}, volume = {17}, number = {1}, year = {2008}, pages = {1{\textendash}20}, keywords = {function of locally varying complexity, hierarchical mixed model, Laplace approximation}, author = {Krivobokova, Tatyana and Crainiceanu, C and Kauermann, G{\"o}ran} } @article {stamatakis2008fasting, title = {Fasting Glycemia in Sleep Disordered Breathing: Lowering the Threshold on Oxyhemoglobin Desaturation}, journal = {Sleep, PMCID: PMC2491502}, volume = {31}, number = {7}, year = {2008}, pages = {1018{\textendash}1024}, publisher = {American Academy of Sleep Medicine}, author = {Stamatakis, K and Sanders, M and Caffo, B and Resnick, H and Gottlieb, D and Mehra, R and Punjabi, N} } @article {suskauer2008fmri, title = {fMRI of Intrasubject Variability in ADHD: Anomalous Premotor Activity With Prefrontal Compensation}, journal = {Journal of American Academy of Child \& Adolescent Psychiatry, NIHMSID: 71813}, volume = {47}, number = {10}, year = {2008}, pages = {1141{\textendash}1150}, author = {Suskauer, S and Simmonds, D and Caffo, B and Denckla, M and Pekar, J and Mostofsky, S} } @article {caffo2008likelihood, title = {Likelihood Estimation of Conjugacy Relationships in Linear Models with Applications to High-Throughput Genomics}, journal = {International Journal of Biostatistics, PMCID: PMC2827886}, volume = {5}, year = {2008}, note = {Issue 18}, publisher = {bepress}, author = {Caffo, B and Dongmei, L and Scharpf, R and Parmigiani, G.} } @article {choi2008mechanistic, title = {A mechanistic latent variable model for estimating drug concentrations in the male genital tract: A case study in drug kinetics}, journal = {Statistics in Medicine, PMCID: PMC2763330}, volume = {27}, number = {14}, year = {2008}, pages = {2697{\textendash}2714}, publisher = {John Wiley \& Sons, Ltd Chichester, UK}, author = {Choi, L and Caffo, B and Rohde, C and Ndovi, T and Hendrix, C} } @article {pmid18552590, title = {Model selection and health effect estimation in environmental epidemiology}, journal = {Epidemiology}, volume = {19}, number = {4}, year = {2008}, month = {Jul}, pages = {558{\textendash}560}, author = {Dominici, F. and Wang, C. and Crainiceanu, C and Parmigiani, G.} } @article {cao2008noninvasive, title = {Noninvasive Quantitation of Drug Concentration in Prostate and Seminal Vesicles: Improvement and Validation With Desipramine and Aspirin}, journal = {The Journal of Clinical Pharmacology}, volume = {48}, number = {2}, year = {2008}, pages = {176-183}, publisher = {Am Coll Clin Pharm}, author = {Cao, Y and Caffo, B and Choi, L and Radebaugh, C and Fuchs, E and Hendrix, C} } @article {zhang2008power, title = {Power Spectral Analysis of EEG Activity During Sleep in Cigarette Smokers}, journal = {Chest}, volume = {133}, number = {2}, year = {2008}, pages = {427{\textendash}432}, publisher = {Am Coll Chest Phys}, author = {Zhang, L and Samet, J and Caffo, B and Bankman, I and Punjabi, N} } @article {Crai:Digg:Rowl:rejo:2008, title = {Rejoinder}, journal = {Journal of the American Statistical Association}, volume = {103}, number = {481}, year = {2008}, pages = {43{\textendash}43}, author = {Crainiceanu, C and Diggle, Peter J. and Rowlingson, Barry} } @article {Grev:Crai:Kche:Pete:rest:2008, title = {Restricted Likelihood Ratio Testing for Zero Variance Components in Linear Mixed Models}, journal = {Journal of Computational and Graphical Statistics}, volume = {17}, number = {4}, year = {2008}, pages = {870{\textendash}891}, keywords = {Nonparametric smoothing, nonregular problem, parametric bootstrap, penalized splines}, author = {Greven, S. and Crainiceanu, C and K{\"u}chenhoff, Helmut and Peters, Annette} } @article {choi2008survey, title = {A survey of the likelihood approach to bioequivalence trials}, journal = {Statistics in Medicine, PMCID: PMC2778077}, volume = {27}, number = {24}, year = {2008}, pages = {4874{\textendash}4894}, publisher = {John Wiley \& Sons, Ltd Chichester, UK}, author = {Choi, L and Caffo, B and Rohde, C} } @article {he2008toward, title = {Toward Realistic and Practical Ideal Observer (IO) Estimation for the Optimization of Medical Imaging Systems}, journal = {IEEE Transactions on Medical Imaging, PMCID: PMC2739397}, volume = {27}, number = {10}, year = {2008}, pages = {1535{\textendash}1543}, author = {He, X and Caffo, B and Frey, E} } @article {caffo2007brain, title = {Are Brain Volumes based on Magnetic Resonance Imaging Mediators of the Associations of Cumulative Lead Dose with Cognitive Function?}, journal = {American Journal of Epidemiology}, volume = {167}, number = {4}, year = {2007}, pages = {429{\textendash}437}, publisher = {Oxford Univ Press}, author = {Caffo, B and Chen, S and Stewart, W and Bolla, K and Yousem, D and Davatzikos, C. and Schwartz, B} } @article {Vogelstein2007, title = {Dynamically reconfigurable silicon array of spiking neurons with conductance-based synapses.}, journal = {IEEE Transactions on Neural Networks}, volume = {18}, number = {1}, year = {2007}, pages = {253{\textendash}65}, publisher = {IEEE INSTITUTE OF ELECTRICAL AND ELECTRONICS}, abstract = {

A mixed-signal very large scale integration (VLSI) chip for large scale emulation of spiking neural networks is presented. The chip contains 2400 silicon neurons with fully programmable and reconfigurable synaptic connectivity. Each neuron implements a discrete-time model of a single-compartment cell. The model allows for analog membrane dynamics and an arbitrary number of synaptic connections, each with tunable conductance and reversal potential. The array of silicon neurons functions as an address-event (AE) transceiver, with incoming and outgoing spikes communicated over an asynchronous event-driven digital bus. Address encoding and conflict resolution of spiking events are implemented via a randomized arbitration scheme that ensures balanced servicing of event requests across the array. Routing of events is implemented externally using dynamically programmable random-access memory that stores a postsynaptic address, the conductance, and the reversal potential of each synaptic connection. Here, we describe the silicon neuron circuits, present experimental data characterizing the 3 mm x 3 mm chip fabricated in 0.5-microm complementary metal-oxide-semiconductor (CMOS) technology, and demonstrate its utility by configuring the hardware to emulate a model of attractor dynamics and waves of neural activity during sleep in rat hippocampus.

}, issn = {10459227}, doi = {10.1109/TNN.2006.883007}, url = {http://www.ncbi.nlm.nih.gov/pubmed/17278476}, author = {Vogelstein, Joshua T and Mallik, Udayan and Vogelstein, Joshua T and Cauwenberghs, Gert} } @article {cao2007effect, title = {Effect of semen sampling frequency on seminal antiretroviral drug concentration}, journal = {Clinical Pharmacology \& Therapeutics}, volume = {83}, number = {6}, year = {2007}, pages = {848{\textendash}856}, publisher = {Nature Publishing Group}, author = {Cao, Y and Ndovi, T and Parsons, T and Guidos, A and Caffo, B and Hendrix, C} } @article {caffo2007flexible, title = {Flexible random intercept models for binary outcomes using mixtures of normals}, journal = {Computational Statistics and Data Analysis, PMCID: PMC2031853}, volume = {51}, number = {11}, year = {2007}, pages = {5220{\textendash}5235}, publisher = {Elsevier}, author = {Caffo, B and An, M and Rohde, C} } @article {ndovi2007new, title = {A new method to estimate quantitatively seminal vesicle and prostate gland contributions to ejaculate}, journal = {British Journal of Clinical Pharmacology, PMCID: PMC2203235}, volume = {63}, number = {4}, year = {2007}, pages = {404-420}, publisher = {Blackwell Publishing}, author = {Ndovi, T and Parsons, T and Choi, L and Caffo, B and Rohde, C and Hendrix, C} } @article {Crai:nonp:2007, title = {Nonparametric Regression Methods for Longitudinal Data Analysis. Mixed-effects Modeling Approaches: Hulin Wu and Jin-Ting Zhang}, journal = {Journal of the American Statistical Association}, volume = {102}, number = {478}, year = {2007}, pages = {761{\textendash}761}, author = {Crainiceanu, C} } @article {choi2007optimal, title = {Optimal sampling times in bioequivalence studies using a simulated annealing algorithm}, journal = {Statistics and Computing}, volume = {17}, number = {4}, year = {2007}, pages = {337{\textendash}347}, publisher = {Springer}, author = {Choi, L and Caffo, B and Rohde, C} } @article {li2007potential, title = {On the potential for ill logic with logically defined outcomes}, journal = {Biostatistics}, volume = {8}, number = {4}, year = {2007}, pages = {800}, author = {Li, X and Caffo, B and Scharfstein, D} } @article {pmid17344421, title = {Reduced kidney function as a risk factor for incident heart failure: the atherosclerosis risk in communities (ARIC) study}, journal = {J. Am. Soc. Nephrol.}, volume = {18}, number = {4}, year = {2007}, month = {Apr}, pages = {1307{\textendash}1315}, author = {Kottgen, A. and Russell, S. D. and Loehr, L. R. and Crainiceanu, C and Rosamond, W. D. and Chang, P. P. and Chambless, L. E. and Coresh, J.} } @article {schwartz2007relations, title = {Relations of brain volumes with cognitive function in males 45 years and older with past lead exposure}, journal = {Neuroimage, PMCID: PMC2038986}, volume = {37}, number = {2}, year = {2007}, pages = {633{\textendash}641}, publisher = {Elsevier}, author = {Schwartz, B and Chen, S and Caffo, B and Stewart, W and Bolla, K and Yousem, D and Davatzikos, C.} } @article {pmid17646610, title = {Short-term variability in measures of glycemia and implications for the classification of diabetes}, journal = {Arch. Intern. Med.}, volume = {167}, number = {14}, year = {2007}, month = {Jul}, pages = {1545{\textendash}1551}, author = {Selvin, E. and Crainiceanu, C and Brancati, F. L. and Coresh, J.} } @article {Crai:Rupp:Carr:Josh:Good:spat:2007, title = {Spatially Adaptive Bayesian Penalized Splines with Heteroscedastic Errors}, journal = {Journal of Computational and Graphical Statistics}, volume = {16}, number = {2}, year = {2007}, pages = {265{\textendash}288}, keywords = {Heteroscedasticity, MCMC, Multivariate smoothing, Regression splines, spatially adaptive penalty, thin-plate splines, Variance functions}, author = {Crainiceanu, C and Ruppert, D. and Carroll, Raymond J. and Joshi, Adarsh and Goodner, Billy} } @article {zhang2006cigarette, title = {Cigarette smoking and nocturnal sleep architecture}, journal = {American Journal of Epidemiology}, volume = {164}, number = {6}, year = {2006}, pages = {529}, publisher = {Oxford Univ Press}, author = {Zhang, L and Samet, J and Caffo, B and Punjabi, N} } @article {caffo2006exact, title = {Exact Hypothesis Tests for Log-linear Models with exactLoglinTest}, journal = {Journal of Statistical Software}, volume = {17}, number = {7}, year = {2006}, pages = {1{\textendash}17}, author = {Caffo, B} } @article {bassett2006familial, title = {Familial risk for Alzheimer{\textquoteright}s disease alters fMRI activation patterns}, journal = {Brain, PMCID: PMC2744898}, volume = {129}, number = {5}, year = {2006}, pages = {1229{\textendash}1239}, publisher = {Oxford Univ Press}, author = {Bassett, S and Yousem, D and Cristinzio, C and Kusevic, I and Yassa, M and Caffo, B and Zeger, S} } @article {jones2006fixed, title = {Fixed-width output analysis for Markov chain Monte Carlo}, journal = {Journal of the American Statistical Association}, volume = {101}, number = {476}, year = {2006}, pages = {1537{\textendash}1547}, publisher = {ASA}, author = {Jones, G and Haran, M and Caffo, B and Neath, R} } @article {ndovi2006quantitative, title = {Quantitative assessment of seminal vesicle and prostate drug concentrations by use of a noninvasive method}, journal = {Clinical Pharmacology \& Therapeutics}, volume = {80}, number = {2}, year = {2006}, pages = {146{\textendash}158}, publisher = {Nature Publishing Group}, author = {Ndovi, T and Choi, L and Caffo, B and Parsons, T and Baker, S and Zhao, M and Rohde, C and Hendrix, C} } @article {Gime:Crai:Barb:Jeno:Morg:semi:2006, title = {Semiparametric Regression in Capture\textndashrecapture Modeling}, journal = {Biometrics}, volume = {62}, number = {3}, year = {2006}, pages = {691{\textendash}698}, keywords = {auxiliary variables, Bayesian inference, Demographic rates, Environmental covariates, penalized splines, Winbugs}, author = {Gimenez, O. and Crainiceanu, C and Barbraud, C. and Jenouvrier, S. and Morgan, B. J. T.} } @article {caffo2006user, title = {A user-friendly tutorial on link-probit-normal models}, journal = {The American Statistician}, volume = {60}, year = {2006}, pages = {139{\textendash}145}, author = {Caffo, B and Griswold, M} } @article {caffo2005ascent, title = {Ascent-Based Monte Carlo EM}, journal = {Journal of the Royal Statistical Society, Series B}, volume = {67}, year = {2005}, pages = {235{\textendash}252}, author = {Caffo, B and Jank, W and Jones, G} } @article {pmid15817517, title = {Electrocorticographic high gamma activity versus electrical cortical stimulation mapping of naming}, journal = {Brain}, volume = {128}, number = {Pt 7}, year = {2005}, month = {Jul}, pages = {1556{\textendash}1570}, author = {Sinai, A. and Bowers, C. W. and Crainiceanu, C and Boatman, D. and Gordon, B. and Lesser, R. P. and Lenz, F. A. and Crone, N.E.} } @article {Crai:Rupp:Clae:Wand:exac:2005, title = {Exact Likelihood Ratio Tests for Penalised Splines}, journal = {Biometrika}, volume = {92}, number = {1}, year = {2005}, pages = {91{\textendash}103}, keywords = {Linear mixed model, Penalised spline, Smoothing, Zero variance component}, author = {Crainiceanu, C and Ruppert, D. and Claeskens, Gerda and Wand, M. P.} } @article {agresti2004examples, title = {Examples in which misspecification of a random effects distribution reduces efficiency, and possible remedies}, journal = {Computational Statistics and Data Analysis}, volume = {47}, number = {3}, year = {2004}, pages = {639{\textendash}653}, publisher = {Elsevier}, author = {Agresti, A and Caffo, B and Ohman-Strickland, P} } @article {Crai:Rupp:like:2004, title = {Likelihood Ratio Tests in Linear Mixed Models with One Variance Component}, journal = {Journal of the Royal Statistical Society, Series B: Statistical Methodology}, volume = {66}, number = {1}, year = {2004}, pages = {165{\textendash}185}, keywords = {Degrees of freedom, Non-regular problems, penalized splines}, author = {Crainiceanu, C and Ruppert, D.} } @article {Carr:Rupp:Crai:Tost:Kara:nonl:2004, title = {Nonlinear and Nonparametric Regression and Instrumental Variables}, journal = {Journal of the American Statistical Association}, volume = {99}, number = {467}, year = {2004}, pages = {736{\textendash}750}, keywords = {Bayesian methods, Identifiability, Measurement error, Simulation extrapolation, Splines, structural modeling}, author = {Carroll, Raymond J. and Ruppert, D. and Crainiceanu, C and Tosteson, Tor D. and Karagas, Margaret R.} } @article {Crai:Rupp:rest:2004, title = {Restricted Likelihood Ratio Tests in Nonparametric Longitudinal Models}, journal = {Statistica Sinica}, volume = {14}, number = {3}, year = {2004}, pages = {713{\textendash}729}, keywords = {Bootstrap, linear mixed models, non-standard asymptotics, penalized splines, subject-specific curves, Variance components}, author = {Crainiceanu, C and Ruppert, D.} } @article {caffo2003monte, title = {Monte Carlo conditional inference for log-linear and logistic models: a survey of current methodology}, journal = {Statistical Methods in Medical Research}, volume = {12}, number = {2}, year = {2003}, pages = {109}, author = {Caffo, B and Booth, J} } @article {pmid12941553, title = {Prevalence estimates for paratuberculosis adjusted for test variability using Bayesian analysis}, journal = {Prev. Vet. Med.}, volume = {60}, number = {4}, year = {2003}, month = {Sep}, pages = {281{\textendash}295}, author = {van Schaik, G. and Schukken, Y. H. and Crainiceanu, C and Muskens, J. and VanLeeuwen, J. A.} } @article {caffo2002empirical, title = {Empirical supremum rejection sampling}, journal = {Biometrika}, volume = {89}, number = {4}, year = {2002}, pages = {745{\textendash}754}, publisher = {Biometrika Trust}, author = {Caffo, B and Booth, J and Davison, A} } @conference {Crai:Rupp:Sted:Behr:impr:2002, title = {Improving MCMC Mixing for a GLMM Describing Pathogen Concentrations in Water Supplies}, booktitle = {Case Studies in Bayesian Statistics, Volume V (Lecture Notes in Statistics Vol. 162)}, year = {2002}, pages = {207{\textendash}221}, publisher = {Springer-Verlag Inc}, organization = {Springer-Verlag Inc}, keywords = {Ecology}, author = {Crainiceanu, C and Ruppert, D. and Stedinger, Jery R. and Behr, Christopher T.} } @article {agresti2002measures, title = {Measures of relative model fit}, journal = {Computational Statistics and Data Analysis}, volume = {39}, number = {2}, year = {2002}, pages = {127{\textendash}136}, publisher = {Elsevier}, author = {Agresti, A and Caffo, B} } @article {booth2002unequal, title = {Unequal sampling for Monte Carlo EM algorithms}, journal = {Computational Statistics and Data Analysis}, volume = {39}, number = {3}, year = {2002}, pages = {261{\textendash}270}, publisher = {Elsevier}, author = {Booth, J and Caffo, B} } @article {caffo2001markov, title = {A Markov chain Monte Carlo algorithm for approximating exact conditional probabilities}, journal = {Journal of Computational and Graphical Statistics}, volume = {10}, number = {4}, year = {2001}, pages = {730{\textendash}745}, publisher = {ASA}, author = {Caffo, B and Booth, J} } @article {hartzel2001multinomial, title = {Multinomial logit random effects models}, journal = {Statistical Modelling}, volume = {1}, number = {2}, year = {2001}, pages = {81}, author = {Hartzel, J and Agresti, A and Caffo, B} } @article {agresti2000random, title = {Random-effects modeling of categorical response data}, journal = {Sociological Methodology}, volume = {30}, year = {2000}, pages = {27{\textendash}80}, publisher = {Blackwell Publishers}, author = {Agresti, A and Booth, J and Hobert, J and Caffo, B} } @article {agresti2000simple, title = {Simple and effective confidence intervals for proportions and differences of proportions result from adding two successes and two failures}, journal = {The American Statistician}, volume = {54}, number = {4}, year = {2000}, pages = {280{\textendash}288}, publisher = {American Statistical Association}, author = {Agresti, A and Caffo, B} } @article {Greenspan1997, title = {Loss of FHIT expression in cervical carcinoma cell lines and primary tumors.}, journal = {Cancer Research}, volume = {57}, number = {21}, year = {1997}, pages = {4692{\textendash}4698}, publisher = {Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.}, abstract = {

Allelic deletions involving the short arm of chromosome 3 (3p13-21.1) have been observed frequently in cervical carcinomas. Recently, a candidate tumor suppressor gene, FHIT (Fragile Histidine Triad), was cloned and mapped to this chromosomal region (3p14.2). Abnormal FHIT transcripts have been identified previously in a variety of tumor cell lines and primary carcinomas, although their significance and the molecular mechanisms underlying their origin remain incompletely defined. In addition, integration of human papillomavirus DNA has been identified at a fragile site (FRA3B) within the FHIT locus in cervical cancer. These observations motivated us to evaluate FHIT mRNA and protein expression in cervical cancer cell lines, primary cervical carcinomas, and normal tissues. Transcripts of the expected size and sequence were the predominant species identified by reverse transcription (RT)-PCR in cultured keratinocytes and all normal tissues evaluated. In contrast, aberrant FHIT transcripts were readily demonstrated in 6 of 7 cervical carcinoma cell lines and 17 of 25 (68\%) primary cervical carcinomas. Northern blot analyses demonstrated reduced or absent FHIT expression in the cervical carcinoma cell lines, particularly those with aberrant RT-PCR products. Immunohistochemical analysis of Fhit expression in cervical tissues revealed strong immunoreactivity in nonneoplastic squamous and glandular cervical epithelium and marked reduction or loss of Fhit protein in 25 of 33 (76\%) primary cervical carcinomas. In those cervical cancer cell lines and primary tumors with exclusively aberrant or absent FHIT transcripts by RT-PCR, Fhit protein expression was always markedly reduced or absent. The frequent alterations in FHIT expression in many cervical carcinomas, but not in normal tissues, suggest that FHIT gene alterations may play an important role in cervical tumorigenesis.

}, url = {http://www.ncbi.nlm.nih.gov/pubmed/9354423}, author = {Greenspan, D L and Connolly, D C and Wu, R and Lei, R Y and Vogelstein, Joshua T and Kim, Y T and Mok, J E and Mu{\~n}oz, N and Bosch, F X and Shah, K and Cho, K R} }