@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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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. M. and Calabresi, P and Saidha, S.} } @article {harrison, title = {Longitudinal changes in diffusion-tensor-based quantitative MRI in multiple sclerosis}, journal = {Neurology, PMCID: PMC3030233}, volume = {76}, year = {2011}, pages = {179{\textendash}186}, author = {Harrison, D and Caffo, B and Shiee, N and Farrell, J Bazin, P and Farrell, S and Ratchford, J and Calabresi, P and Reich, D.} } @article {nazarian2011AI, title = {Prospective study to assess the safety of a protocol for magnetic resonance imaging of patients with implanted cardiac devices}, journal = {Annals of Interal Medicine}, volume = {155}, number = {7}, year = {2011}, pages = {415{\textendash}424}, publisher = {American College of Physicians}, author = {Nazarian, S and Hansford, R and Roguin, A and Goldsher, D and Zviman, M and Lardo, A and Caffo, B and Frick, K and Kraut, M and Kamel, I and Ihab, R and Calkins, H and Berger, R and Bluemke, D and Halperin, H} } @article {Paninski2010, title = {A new look at state-space models for neural data.}, journal = {Journal of computational neuroscience}, volume = {29}, number = {1-2}, year = {2010}, pages = {107{\textendash}26}, abstract = {

State space methods have proven indispensable in neural data analysis. However, common methods for performing inference in state-space models with non-Gaussian observations rely on certain approximations which are not always accurate. Here we review direct optimization methods that avoid these approximations, but that nonetheless retain the computational efficiency of the approximate methods. We discuss a variety of examples, applying these direct optimization techniques to problems in spike train smoothing, stimulus decoding, parameter estimation, and inference of synaptic properties. Along the way, we point out connections to some related standard statistical methods, including spline smoothing and isotonic regression. Finally, we note that the computational methods reviewed here do not in fact depend on the state-space setting at all; instead, the key property we are exploiting involves the bandedness of certain matrices. We close by discussing some applications of this more general point of view, including Markov chain Monte Carlo methods for neural decoding and efficient estimation of spatially-varying firing rates.

}, keywords = {1 introduction, Action Potentials, Action Potentials: physiology, Animals, Computer Simulation, for inference in state-space, forward-backward methods, hidden markov model, models, neural coding, Neurological, Neurons, Neurons: physiology, Retinal Ganglion Cells, Retinal Ganglion Cells: physiology, state-space models, Statistical, Synapses, Synapses: physiology, tridiagonal matrix}, issn = {1573-6873}, doi = {10.1007/s10827-009-0179-x}, url = {http://www.ncbi.nlm.nih.gov/pubmed/19649698}, author = {Paninski, Liam and Ahmadian, Yashar and Gil, Daniel and Shinsuke, Ferreira and Rahnama, Kamiar and Michael, Rad and Vogelstein, Joshua T and Wu, Wei and Ferreira, Daniel Gil and Koyama, Shinsuke and {Rahnama Rad}, Kamiar and Vidne, Michael} } @article {boatman, title = {Quantifying Auditory Event-Related Responses in Multichannel Human Intracranial Recordings}, journal = {Invited submission to Frontiers in Computational Neuroscience, PMCID: PMC2859880}, volume = {4}, number = {4}, year = {2010}, pages = {1{\textendash}17}, author = {Boatman-Reich, D and Franaszczuk, Piotr J. and Korzeniewska, A. and Caffo, B and Ritzl, E and Colwell, S and Crone, N} } @article {hao, title = {Redefining CpG Islands Using a Hidden Markov Models}, journal = {Biostatistics, PMCID: PMC2883304}, volume = {11}, number = {3}, year = {2010}, pages = {499{\textendash}514}, author = {Wu, H and Caffo, B and Jaffee, H and Feinberg, A and Irizarry, R} } @article {frfrst2010, title = {The second order ancillary}, journal = {Bernoulli}, volume = {16}, year = {2010}, pages = {1208{\textendash}1223}, author = {Fraser, A.M. and Fraser, D.A.S. and Staicu, A. M.} } @article {Wager09a, title = {Brain mediators of cardiovascular responses to social threat, Part I: Reciprocal dorsal and ventral sub-regions of the medial prefrontal cortex and heart-rate reactivity}, journal = {NeuroImage}, volume = {47}, year = {2009}, pages = {821-835}, author = {Wager, T.D. and Waugh, C.E. and Lindquist, Martin A and Noll, D.C. and Fredrickson, B.L. and Taylor, S.F.} } @article {pmid19750109, title = {Urine arsenic concentrations and species excretion patterns in American Indian communities over a 10-year period: the Strong Heart Study}, journal = {Environ. Health Perspect.}, volume = {117}, number = {9}, year = {2009}, month = {Sep}, pages = {1428{\textendash}1433}, author = {Navas-Acien, A. and Umans, J. G. and Howard, B. V. and Goessler, W. and Francesconi, K. A. and Crainiceanu, C and Silbergeld, E. K. and Guallar, E.} } @article {grinband2008detection, title = {Detection of time-varying signals in event-related fMRI designs}, journal = {Neuroimage}, volume = {43}, number = {3}, year = {2008}, pages = {509{\textendash}520}, publisher = {Elsevier}, author = {Grinband, Jack and Wager, Tor D and Lindquist, Martin A and Ferrera, Vincent P and Hirsch, Joy} } @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 {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 {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} }