A saturated map of common genetic variants associated with human height.

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.

Methods for estimating insulin resistance from untargeted metabolomics data.

CONTEXT: Insulin resistance is associated with multiple complex diseases; however, precise measures of insulin resistance are invasive, expensive, and time-consuming. OBJECTIVE: Develop estimation models for measures of insulin resistance, including insulin sensitivity index (SI) and homeostatic model assessment of insulin resistance (HOMA-IR) from metabolomics data. DESIGN: Insulin Resistance Atherosclerosis Family Study (IRASFS). SETTING: Community based. PARTICIPANTS: Mexican Americans (MA) and African Americans (AA). MAIN OUTCOME: Estimation models for measures of insulin resistance, i.e. SI and HOMA-IR. RESULTS: Least Absolute Shrinkage and Selection Operator (LASSO) and Elastic Net regression were used to build insulin resistance estimation models from 1274 metabolites combined with clinical data, e.g. age, sex, body mass index (BMI). Metabolite data were transformed using three approaches, i.e. inverse normal transformation, standardization, and Box Cox transformation. The analysis was performed in one MA recruitment site (San Luis Valley, Colorado (SLV); N = 450) and tested in another MA recruitment site (San Antonio, Texas (SA); N = 473). In addition, the two MA recruitment sites were combined and estimation models tested in the AA recruitment sample (Los Angeles, California; N = 495). Estimated and empiric SI were correlated in the SA (r2 = 0.77) and AA (r2 = 0.74) testing datasets. Further, estimated and empiric SI were consistently associated with BMI, low-density lipoprotein cholesterol (LDL), and triglycerides. We applied similar approaches to estimate HOMA-IR with similar results. CONCLUSIONS: We have developed a method for estimating insulin resistance with metabolomics data that has the potential for application to a wide range of biomedical studies and conditions.

Telehealth Use and Access to Neurology Outpatient Clinical Services for Children: An Observational Cohort Study.

Background: Access to neurology services is important for children's well-being. We sought to evaluate the effects of telehealth on pedi-atric neurology appointment outcomes for children. Methods: Using electronic health record (EHR) data, information about children with pediatric neurology appointments in a tertiary care children's hospital in North Carolina was collected. Appointment outcomes (completion, cancellation, and no-show rates) were calculated for children who had a neurology appointment scheduled both in the pre-pandemic (March 10, 2019, to March 9, 2020) and pandemic (March 10, 2020, to March 9, 2021) periods. "Telehealth user" was a child who had at least one telehealth appointment scheduled between March 10, 2020, and March 9, 2021. In bivariate and multivariate analyses, we compared appointment outcomes for telehealth users and non-users. Limitations: EHR data were limited to a single institution and could have missed children's clinical encounters elsewhere. Since this study used secondary data that were not collected for research purposes, it is possible that there were unmeasured confounders. Because of the observational nature of the study, the association between telehealth use and appointment outcomes does not indicate causation. Results: A total of 2110 children had 11,194 pediatric neurology appointments scheduled. Telehealth users compared with non-users were more likely to be White, non-Hispanic, have private insurance, and live farther from the children's hospital. There was a statistically sig-nificant decrease in completion (66% versus 57%) and increase in cancellation (27% versus 33%) and no-show (7% versus 10%) rates in the pandemic when compared to the pre-pandemic period. In the pre-pandemic period, telehealth user and non-user groups had similar cancellation and no-show rates. In the pandemic period, there was a statistically significant decrease in cancellation and no-show rates in the telehealth user group when compared to the non-user group. Conclusions: Pediatric neurology outpatient clinic visits decreased substantially during the pandemic. Telehealth mitigated these problems. Children belonging to a minority race/ethnicity are less likely to use telehealth, increasing their risk of poor access to neurology services.

Longitudinal partially ordered data analysis for preclinical sarcopenia.

Sarcopenia is a geriatric syndrome characterized by significant loss of muscle mass. Based on a commonly used definition of the condition that involves three measurements, different subclinical and clinical states of sarcopenia are formed. These states constitute a partially ordered set (poset). This article focuses on the analysis of longitudinal poset in the context of sarcopenia. We propose an extension of the generalized linear mixed model and a recoding scheme for poset analysis such that two submodels-one for ordered categories and one for nominal categories-that include common random effects can be jointly estimated. The new poset model postulates random effects conceptualized as latent variables that represent an underlying construct of interest, that is, susceptibility to sarcopenia over time. We demonstrate how information can be gleaned from nominal sarcopenic states for strengthening statistical inference on a person's susceptibility to sarcopenia.

Gleaning Information for Cognitive Operations from Don't Know Responses in Cognitive and Noncognitive Assessments.

The Don't Know (DK) response - taking the form of an omitted response or not-reached at the end of a cognitive test, or explicitly presented as a response option in a social survey - contains important information that is often overlooked. Direct psychometric modeling efforts for DK responses are few and far between. In this article, the linear logistic test model (LLTM) is proposed for delineating the impacts of cognitive operations for a test that contains DK responses. We assume that the DK response is a valid response. The assumption is reasonable for many situations, including low-stakes cognitive tests and attitudinal assessments. By extracting information embedded in the DK response, the method shows how DK can inform the latent construct of interest and the cognitive operations underlying the response to stimuli. Using a proven recoding scheme, the LLTM could be implemented through commonly used programs such as PROC GLIMMIX. Two simulation experiments to evaluate how well the parameters can be recovered were conducted. In addition, two real data examples, from a noncognitive test of health belief assessment and a cognitive test of knowledge in diabetes, are also presented as case studies to illustrate the LLTM for DK response.

Predictors of Change in Physical Function in Older Adults in Response to Long-Term, Structured Physical Activity: The LIFE Study.

OBJECTIVES: To evaluate the extent of variability in functional responses in participants in the Lifestyle Interventions and Independence for Elders (LIFE) study and to identify the relative contributions of intervention adherence, physical activity, and demographic and health characteristics to this variability. DESIGN: Secondary analysis. SETTING: Multicenter institutions. PARTICIPANTS: A volunteer sample (N=1635) of sedentary men and women aged 70 to 89 years who were able to walk 400m but had physical limitations, defined as a Short Physical Performance Battery (SPPB) score of ≤9. INTERVENTIONS: Moderate-intensity physical activity (n=818) consisting of aerobic, resistance, and flexibility exercises performed both center-based (2times/wk) and home-based (3-4times/wk) sessions or health education program (n=817) consisting of weekly to monthly workshops covering relevant health information. MAIN OUTCOME MEASURES: Physical function (gait speed over 400m) and lower extremity function (SPPB score) assessed at baseline and 6, 12, and 24 months. RESULTS: Greater baseline physical function (gait speed, SPPB score) was negatively associated with change in gait speed (regression coefficient ß=-.185; P<.001) and change in SPPB score (ß=-.365; P<.001), whereas higher number of steps per day measured by accelerometry was positively associated with change in gait speed (ß=.035; P<.001) and change in SPPB score (ß=.525; P<.001). Other baseline factors associated with positive change in gait speed and/or SPPB score include younger age (P<.001), lower body mass index (P<.001), and higher self-reported physical activity (P=.002). CONCLUSIONS: Several demographic and physical activity-related factors were associated with the extent of change in functional outcomes in participants in the LIFE study. These factors should be considered when designing interventions for improving physical function in older adults with limited mobility.

Effect of Structured Physical Activity on Overall Burden and Transitions Between States of Major Mobility Disability in Older Persons: Secondary Analysis of a Randomized Trial.

Background: The total time a patient is disabled likely has a greater influence on his or her quality of life than the initial occurrence of disability alone. Objective: To compare the effect of a long-term, structured physical activity program with that of a health education intervention on the proportion of patient assessments indicating major mobility disability (MMD) (that is, MMD burden) and on the risk for transitions into and out of MMD. Design: Single-blinded, parallel-group, randomized trial. (ClinicalTrials.gov: NCT01072500). Setting: 8 U.S. centers between February 2010 and December 2013. Participants: 1635 sedentary persons, aged 70 to 89 years, who had functional limitations but could walk 400 m. Intervention: Physical activity (n = 818) and health education (n = 817). Measurements: MMD, defined as the inability to walk 400 m, was assessed every 6 months for up to 3.5 years. Results: During a median follow-up of 2.7 years, the proportion of assessments showing MMD was substantially lower in the physical activity (0.13 [95% CI, 0.11 to 0.15]) than the health education (0.17 [CI, 0.15 to 0.19]) group, yielding a risk ratio of 0.75 (CI, 0.64 to 0.89). In a multistate model, the hazard ratios for comparisons of physical activity with health education were 0.87 (CI, 0.73 to 1.03) for the transition from no MMD to MMD; 0.52 (CI, 0.10 to 2.67) for no MMD to death; 1.33 (CI, 0.99 to 1.77) for MMD to no MMD; and 1.92 (CI, 1.15 to 3.20) for MMD to death. Limitation: The intention-to-treat principle was maintained for MMD burden and first transition out of no MMD, but not for subsequent transitions. Conclusion: A structured physical activity program reduced the MMD burden for an extended period, in part through enhanced recovery after the onset of disability and diminished risk for subsequent disability episodes. Primary Funding Source: National Institute on Aging, National Institutes of Health.

Behavior of the Gibbs Sampler When Conditional Distributions Are Potentially Incompatible.

The Gibbs sampler has been used extensively in the statistics literature. It relies on iteratively sampling from a set of compatible conditional distributions and the sampler is known to converge to a unique invariant joint distribution. However, the Gibbs sampler behaves rather differently when the conditional distributions are not compatible. Such applications have seen increasing use in areas such as multiple imputation. In this paper, we demonstrate that what a Gibbs sampler converges to is a function of the order of the sampling scheme. Besides providing the mathematical background of this behavior, we also explain how that happens through a thorough analysis of the examples.

Psychometric properties of a computerized adaptive test for assessing mobility in older adults using novel video-animation technology.

PURPOSE: This paper reports on the psychometric properties of a computerized adaptive test (CAT) version of the Mobility Assessment Tool (MAT) for older adults (MAT-CAT). METHODS: An item pool of 78 video-animation-based items for mobility was developed, and response data were collected from a sample of 234 participants aged 65-90 years. The video-animation-based instrument was designed to minimize ambiguity in the presentation of task demands. In addition to evaluating traditional psychometric properties including dimensionality, differential item functioning (DIF), and local dependence, we extensively tested the performance of several MAT-CAT measures and compared their performances with a fixed format. RESULTS: Operationally, the MAT-CAT was sufficiently unidimensional and had acceptable levels of local independence. One DIF item was removed. Most importantly, the CAT measures showed that even starting with a single fixed item at the mean ability, the adaptive version delivered better performance than the fixed format in terms of several criteria including the standard error of estimate. CONCLUSION: The MAT-CAT demonstrated satisfactory psychometric properties and superior performance to a fixed format. The video-animation-based adaptive instrument can be used for assessing mobility with specificity and precision.

Audio or Video? Access to Pediatric Neurology Outpatient Services Varies by the Type of Telehealth, Especially for Black Children.

BACKGROUND: Children of minority race/ethnicity face barriers to accessing specialty services. During the COVID pandemic, health insurance companies reimbursed telehealth services. Our objective was to evaluate the effect of audio versus video visits on children's access to outpatient neurology services, particularly for Black children. METHODS: Using Electronic Health Record data, we collected information about children who had outpatient neurology appointments in a tertiary care children's hospital in North Carolina from March 10, 2020, to March 9, 2021. We used multivariable models to compare appointment outcomes (canceled vs completed, and missed vs completed) by visit type. We then conducted similar evaluation for the subgroup of Black children. RESULTS: A total of 1250 children accounted for 3829 scheduled appointments. Audio users were more likely to be Black and Hispanic, and to have public health insurance than video users. Adjusted odds ratio (aOR) for appointments completed versus canceled was 10 for audio and 6 for video, compared to in-person appointments. Audio visits were twice as likely as in-person visits to be completed versus missed; video visits were not different. For the subgroup of Black children, aOR for appointments completed versus canceled for audio was 9 and video was 5, compared to in-person appointments. For Black children, audio visits were 3 times as likely as in-person visits to be completed versus missed; video visits were not different. CONCLUSIONS: Audio visits improved access to pediatric neurology services, especially for Black children. Reversal of policies to reimburse audio visits could deepen the socioeconomic divide for children's access to neurology services.

Structured Moderate Exercise and Biomarkers of Kidney Health in Sedentary Older Adults: The Lifestyle Interventions and Independence for Elders Randomized Clinical Trial.

Rationale & Objective: In the Lifestyle Interventions and Independence for Elders (LIFE) trial, a structured exercise intervention slowed kidney function decline in sedentary older adults. Biomarkers of kidney health could distinguish potential mechanisms for this beneficial effect. Study Design: Randomized controlled trial. Setting & Population: A total of 1,381 sedentary adults aged 70-89 years enrolled in the LIFE trial. Intervention: Structured, 2-year, moderate-intensity exercise intervention versus health education. Outcomes: Physical activity was measured by step count. Primary outcomes were changes in 14 serum and urine biomarkers of kidney health collected at baseline, year 1, and year 2. We determined the effect of randomization on changes in kidney measures and then evaluated observational associations of achieved activity on each measure. Results: Participants assigned to exercise walked on average 291 more steps per day than participants assigned to health education. The intervention was not significantly associated with changes in biomarkers of kidney health. In observational analyses, persons in the highest versus lowest quartile of activity (≥3,470 vs <1,568 steps/day) had significant improvement in urine albumin (mean, -0.22 mg albumin/g urine creatinine [interquartile range (IQR), -0.37 to -0.06]), alpha-1-microglobulin (-0.18 mg/L [-0.28 to -0.08]), trefoil factor-3 (-0.24 pg/mL [-0.35 to -0.13]), epidermal growth factor (0.19 pg/mL [0.06-0.32]), uromodulin (0.06 pg/mL [0.00-0.12]), interleukin 18 (-0.09 pg/mL [-0.15 to -0.03]), neutrophil gelatinase-associated lipocalin (-0.16 pg/mL [-0.24 to -0.07]), monocyte chemoattractant protein-1 (-0.25 pg/mL [-0.36 to -0.14]), clusterin (-0.16 pg/mL [-0.30 to -0.02]), serum tumor necrosis factor receptor-1 (-0.25 mg/dL [-0.39 to -0.11]) and tumor necrosis factor receptor-2 (-0.30 mg/dL [-0.44 to -0.16]). In sensitivity analyses, incremental changes in activity were most impactful on urine interleukin 18 and serum tumor necrosis factor-1. Limitations: The original study was not designed to assess the impact on kidney health. Non-white individuals and patients with advanced chronic kidney disease are underrepresented. Conclusions: Randomization to structured exercise did not improve kidney health at a group level. However, higher exercise was associated with concurrent improvements in biomarkers of glomerular injury, tubular function/repair, tubular injury, generalized inflammation, and tubulointerstitial repair/fibrosis. Plain-Language Summary: In the Lifestyle Interventions For Elders (LIFE) study, randomization to an exercise and physical activity intervention improved the slope of estimated glomerular filtration rate over 2 years compared with health education among older adults. In this study, we sought to determine whether there were specific biomarkers of kidney health that were affected by the exercise and physical activity intervention to investigate potential mechanisms for this positive impact on kidney decline. We found that randomization to the intervention did not improve any of the 14 measures of kidney tubule health. However, in observational analyses, higher activity was independently associated with improvements in several domains, especially tubular injury and generalized inflammation. These results help to clarify the impact of physical activity on kidney health.

Using graded response model for the prediction of prostate cancer risk.

Disease risk-associated single nucleotide polymorphisms (SNPs) identified from genome-wide association studies (GWAS) have the potential to be used for disease risk prediction. An important feature of these risk-associated SNPs is their weak individual effect but stronger cumulative effect on disease risk. To date, a stable summary estimate of the joint effect of genetic variants on disease risk prediction is not available. In this study, we propose to use the graded response model (GRM), which is based on the item response theory, for estimating the individual risk that is associated with a set of SNPs. We compare the GRM with a recently proposed risk prediction model called cumulative relative risk (CRR). Thirty-three prostate cancer risk-associated SNPs were originally discovered in GWAS by December 2009. These SNPs were used to evaluate the performance of GRM and CRR for predicting prostate cancer risk in three GWAS populations, including populations from Sweden, Johns Hopkins Hospital, and the National Cancer Institute Cancer Genetic Markers of Susceptibility study. Computational results show that the risk prediction estimates of GRM, compared to CRR, are less biased and more stable.

Genome-wide two-locus epistasis scans in prostate cancer using two European populations.

Approximately 40 single nucleotide polymorphisms (SNPs) that are associated with prostate cancer (PCa) risk have been identified through genome-wide association studies (GWAS). However, these GWAS-identified PCa risk-associated SNPs can explain only a small proportion of heritability (~13%) of PCa risk. Gene-gene interaction is speculated to be one of the major factors contributing to the so-called missing heritability. To evaluate the gene-gene interaction and PCa risk, we performed a two-stage genome-wide gene-gene interaction scan using a novel statistical approach named "Boolean Operation-based Screening and Testing". In the first stage, we exhaustively evaluated all pairs of SNP-SNP interactions for ~500,000 SNPs in 1,176 PCa cases and 1,101 control subjects from the National Cancer Institute Cancer Genetic Markers of Susceptibility (CGEMS) study. No SNP-SNP interaction reached a genome-wide significant level of 4.4E-13. The second stage of the study involved evaluation of the top 1,325 pairs of SNP-SNP interactions (P(interaction) <1.0E-08) implicated in CGEMS in another GWAS population of 1,964 PCa cases from the Johns Hopkins Hospital (JHH) and 3,172 control subjects from the Illumina iControl database. Sixteen pairs of SNP-SNP interactions were significant in the JHH population at a P(interaction) cutoff of 0.01. However, none of the 16 pairs of SNP-SNP interactions were significant after adjusting for multiple tests. The current study represents one of the first attempts to explore the high-dimensional etiology of PCa on a genome-wide scale. Our results suggested a list of SNP-SNP interactions that can be followed in other replication studies.

Is Wrist Accelerometry Suitable for Threshold Scoring? A Comparison of Hip-Worn and Wrist-Worn ActiGraph Data in Low-Active Older Adults With Obesity.

BACKGROUND: Hip- and wrist-worn ActiGraph accelerometers are widely used in research on physical activity as they offer an objective assessment of movement intensity across the day. Herein we characterize and contrast key structured physical activities and common activities of daily living via accelerometry data collected at the hip and wrist from a sample of community-dwelling older adults. METHODS: Low-active, older adults with obesity (age 60+ years) were fit with an ActiGraph GT3X+ accelerometer on their nondominant wrist and hip before completing a series of tasks in a randomized order, including sitting/standing, sweeping, folding laundry, stair climbing, ambulation at different intensities, and cycling at different intensities. Participants returned a week later and completed the tasks once again. Vector magnitude counts/second were time-matched during each task and then summarized into counts/minute (CPM). RESULTS: Monitors at both wear locations similarly characterized standing, sitting, and ambulatory tasks. A key finding was that light home chores (sweeping, folding laundry) produced higher and more variable CPM values than fast walking via wrist ActiGraph. Regression analyses revealed wrist CPM values were poor predictors of hip CPM values, with devices aligning best during fast walking (R2 = 0.25) and stair climbing (R2 = 0.35). CONCLUSIONS: As older adults spend a considerable portion of their day in nonexercise activities of daily living, researchers should be cautious in the use of simply acceleration thresholds for scoring wrist-worn accelerometer data. Methods for better classifying wrist-worn activity monitor data in older adults are needed.

Evaluation of the Linear Composite Conjecture for Unidimensional IRT Scale for Multidimensional Responses.

The linear composite direction represents, theoretically, where the unidimensional scale would lie within a multidimensional latent space. Using compensatory multidimensional IRT, the linear composite can be derived from the structure of the items and the latent distribution. The purpose of this study was to evaluate the validity of the linear composite conjecture and examine how well a fitted unidimensional IRT model approximates the linear composite direction in a multidimensional latent space. Simulation experiment results overall show that the fitted unidimensional IRT model sufficiently approximates linear composite direction when correlation between bivariate latent variables is positive. When the correlation between bivariate latent variables is negative, instability occurs when the fitted unidimensional IRT model is used to approximate linear composite direction. A real data experiment was also conducted using 20 items from a multiple-choice mathematics test from American College Testing.

Effect of Structured, Moderate Exercise on Kidney Function Decline in Sedentary Older Adults: An Ancillary Analysis of the LIFE Study Randomized Clinical Trial.

Importance: Observational evidence suggests that higher physical activity is associated with slower kidney function decline; however, to our knowledge, no large trial has evaluated whether activity and exercise can ameliorate kidney function decline in older adults. Objective: To evaluate whether a moderate-intensity exercise intervention can affect the rate of estimated glomerular filtration rate per cystatin C (eGFRCysC) change in older adults. Design, Setting, and Participants: This ancillary analysis of the Lifestyle Interventions and Independence For Elders randomized clinical trial enrolled 1199 community-dwelling, sedentary adults aged 70 to 89 years with mobility limitations and available blood specimens. The original trial was conducted across 8 academic centers in the US from February 2010 through December 2013. Data for this study were analyzed from March 29, 2021, to February 28, 2022. Interventions: Structured, 2-year, partially supervised, moderate-intensity physical activity and exercise (strength, flexibility) intervention compared with a health education control intervention with 2-year follow-up. Physical activity was measured by step count and minutes of moderate-intensity activity using accelerometers. Main Outcomes and Measures: The primary outcome was change in eGFRCysC. Rapid eGFRCysC decline was defined by the high tertile threshold of 6.7%/y. Results: Among the 1199 participants in the analysis, the mean (SD) age was 78.9 (5.2) years, and 800 (66.7%) were women. At baseline, the 2 groups were well balanced by age, comorbidity, and baseline eGFRCysC. The physical activity and exercise intervention resulted in statistically significantly lower decline in eGFRCysC over 2 years compared with the health education arm (mean difference, 0.96 mL/min/1.73 m2; 95% CI, 0.02-1.91 mL/min/1.73 m2) and lower odds of rapid eGFRCysC decline (odds ratio, 0.79; 95% CI, 0.65-0.97). Conclusions and Relevance: Results of this ancillary analysis of a randomized clinical trial showed that when compared with health education, a physical activity and exercise intervention slowed the rate of decline in eGFRCysC among community-dwelling sedentary older adults. Clinicians should consider targeted recommendation of physical activity and moderate-intensity exercise for older adults as a treatment to slow decline in eGFRCysC. Trial Registration: ClinicalTrials.gov Identifier: NCT01072500.

Gradient and Acceleration of Decline in Physical and Cognitive Functions in Older Adults: A Disparity Analysis.

BACKGROUND: Substantive previous work has shown that both gait speed and global cognition decline as people age. Rates of their decline, as opposed to cross-sectional measurements, could be more informative of future functional status and other clinical outcomes because they more accurately represent deteriorating systems. Additionally, understanding the sex and racial disparity in the speed of deterioration, if any, is also important as ethnic minorities are at an increased risk of mobility disability and dementia. METHOD: Data from 2 large longitudinal intervention studies were integrated. Rates of decline were derived from individual-level measures of gait speed of 400-m walk and scores on the Modified Mini Mental State Examination (3MSE). We also assessed age-associated declines and accelerations in changes across the ages represented in the studies (age range 53-90). RESULTS: The mean rate of decline in 400-m gait speed across individuals was 0.03 m/s per year, and multivariable analysis showed a significant acceleration in decline of -0.0013 m/s/y2 (p < .001). Both race and sex moderated the rate of decline. For global cognition, the mean rate of decline was 0.05 of a point per year on the 3MSE scale, and acceleration in the rate of decline was significant (-0.017 point/y2, p < .001), but neither sex nor race moderated the decline. CONCLUSION: Rate of decline in physical but not cognitive function appears moderated by sex and race. This finding, as well as rates and accelerations of decline estimated herein, could inform future intervention studies. CLINICAL TRIALS REGISTRATION NUMBER: NCT00017953 (Look AHEAD); NCT01410097 (Look AHEAD ancillary); NCT00116194 (LIFE).

Gibbs Ensembles for Nearly Compatible and Incompatible Conditional Models.

Gibbs sampler has been used exclusively for compatible conditionals that converge to a unique invariant joint distribution. However, conditional models are not always compatible. In this paper, a Gibbs sampling-based approach - Gibbs ensemble -is proposed to search for a joint distribution that deviates least from a prescribed set of conditional distributions. The algorithm can be easily scalable such that it can handle large data sets of high dimensionality. Using simulated data, we show that the proposed approach provides joint distributions that are less discrepant from the incompatible conditionals than those obtained by other methods discussed in the literature. The ensemble approach is also applied to a data set regarding geno-polymorphism and response to chemotherapy in patients with metastatic colorectal.

Conversion between the Modified Mini-Mental State Examination (3MSE) and the Mini-Mental State Examination (MMSE).

BACKGROUND: The Modified Mini-Mental State Examination (3MSE) and the Mini-Mental State Examination (MMSE) are two commonly used instruments for assessing cognitive function. Although conversion between 3MSE and MMSE is useful in applications such as integrative data analysis, there are limited published reports on the topic. Our objective is to provide a dual tool: (1) an item-level conversion tool to score responses for deriving both 3MSE and MMSE measures, and (2) cross-walk tables to facilitate quick conversion between 3MSE and MMSE. METHODS: An SAS program tool allows scoring of 3MSE item-level responses into MMSE score. Using integrated data sets (n = 8346), actual 3MSE and MMSE scores obtained from the same individuals were linked to form cross-walk tables. RESULTS: An SAS conversion program was made available. Cross-walk tables were derived. Validation sample shows bias is -0.11 (standard deviation = 1.02) in 3MSE→MMSE; the converse had substantially large bias. DISCUSSION: The 3MSE→MMSE conversion table can be used in clinical practice and legacy system data.

Association of Objectively Measured Timing of Physical Activity Bouts With Cardiovascular Health in Type 2 Diabetes.

OBJECTIVE: Moderate- to vigorous-intensity physical activity (MVPA) improves cardiovascular health. Few studies have examined MVPA timing. We examined the associations of timing of bout-related MVPA with cardiorespiratory fitness and cardiovascular risk in adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: Baseline 7-day hip-worn accelerometry data from Look AHEAD participants (n = 2,153, 57% women) were analyzed to identify bout-related MVPA (≥3 METs/min for ≥10 min). Cardiorespiratory fitness was assessed by maximal graded exercise test. Participants were categorized into six groups on the basis of the time of day with the majority of bout-related MVPA (METs × min): ≥50% of bout-related MVPA during the same time window (morning, midday, afternoon, or evening), <50% of bout-related MVPA in any time category (mixed; the reference group), and ≤1 day with bout-related MVPA per week (inactive). RESULTS: Cardiorespiratory fitness was highly associated with timing of bout-related MVPA (P = 0.0005), independent of weekly bout-related MVPA volume and intensity. Importantly, this association varied by sex (P = 0.02). In men, the midday group had the lowest fitness (ß = -0.46 [95% CI -0.87, -0.06]), while the mixed group in women was the least fit. Framingham risk score (FRS) was associated with timing of bout-related MVPA (P = 0.02), which also differed by sex (P = 0.0007). The male morning group had the highest 4-year FRS (2.18% [0.70, 3.65]), but no association was observed in women. CONCLUSIONS: Timing of bout-related MVPA is associated with cardiorespiratory fitness and cardiovascular risk in men with type 2 diabetes, independent of bout-related MVPA volume and intensity. Prospective studies are needed to determine the impacts of MVPA timing on cardiovascular health.