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Abstract Background Sedentary behavior (SB) is a recognized risk factor for many chronic diseases. ActiGraph and activPAL are two commonly used wearable accelerometers in SB research. The former measures body movement and the latter measures body posture. The goal of the current study is to quantify the pattern and variation of movement (by ActiGraph activity counts) during activPAL-identified sitting events, and examine associations between patterns and health-related outcomes, such as systolic and diastolic blood pressure (SBP and DBP). Methods The current study included 314 overweight postmenopausal women, who were instructed to wear an activPAL (at thigh) and ActiGraph (at waist) simultaneously for 24 hours a day for a week under free-living conditions. ActiGraph and activPAL data were processed to obtain minute-level time-series outputs. Multilevel functional principal component analysis (MFPCA) was applied to minute-level ActiGraph activity counts within activPAL-identified sitting bouts to investigate variation in movement while sitting across subjects and days. The multilevel approach accounted for the nesting of days within subjects. Results At least 90% of the overall variation of activity counts was explained by two subject-level principal components (PC) and six day-level PCs, hence dramatically reducing the dimensions from the original minute-level scale. The first subject-level PC captured patterns of fluctuation in movement during sitting, whereas the second subject-level PC delineated variation in movement during different lengths of sitting bouts: shorter (< 30 minutes), medium (30 -39 minutes) or longer (> 39 minute). The first subject-level PC scores showed positive association with DBP (standardized $$\hat{\beta }$$ β ^ : 2.041, standard error: 0.607, adjusted p = 0.007), which implied that lower activity counts (during sitting) were associated with higher DBP. Conclusion In this work we implemented MFPCA to identify variation in movement patterns during sitting bouts, and showed that these patterns were associated with cardiovascular health. Unlike existing methods, MFPCA does not require pre-specified cut-points to define activity intensity, and thus offers a novel powerful statistical tool to elucidate variation in SB patterns and health. Trial registration ClinicalTrials.gov NCT03473145; Registered 22 March 2018; https://clinicaltrials.gov/ct2/show/NCT03473145 ; International Registered Report Identifier (IRRID): DERR1-10.2196/28684

Background: Incidence of cardiometabolic disease among U.S. Hispanics/Latinos is higher than in non-Hispanic Whites. Prolonged sitting duration is prevalent in older adults, and compounded with menopause, greatly increases cardiometabolic risk in postmenopausal women. Metabolomic analyses of interventions to reduce sitting are lacking and mechanistic understanding of health-promoting behavior change in postmenopausal Latinas is needed. Methods: To address this knowledge gap, an exploratory analysis investigated the plasma metabolome impact of a 12-week increased standing intervention among sedentary postmenopausal Latinas with overweight or obesity. From a parent-randomized controlled trial, a subset of Best Responders (n = 43) was selected using parameters of highest mean change in sitting bout duration and total sitting time; baseline variable-Matched Controls (n = 43) were selected using random forest modeling. Targeted LC-MS/MS analysis of archived baseline and 12-week plasma samples was conducted. Metabolite change was determined using a covariate-controlled general linear model and multivariate testing was performed. A false discovery rate correction was applied to all analyses. Results: Best Responders significantly changed time sitting (−110.0 ± 11.0 min; −21%), standing (104.6 ± 10.1 min; 40%), and sitting in bouts >30 min (−102.3 ± 13.9 min; −35%) compared to Matched Controls (7.1 ± 9.8 min, −7.8 ± 9.0 min, and −4.6 ± 12.7 min, respectively; all p < 0.001). Twelve-week metabolite change was significantly different between the two groups for 24 metabolites (FDR < 0.05). These were primarily related to amino acid metabolism, improved blood flow, and ATP production. Enzyme enrichment analysis predicted significant changes regulating glutamate, histidine, phenylalanine, and mitochondrial short-chain fatty acid catabolism. Pathway analysis showed significant intervention effects on glutamate metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis, potentially indicating reduced cardiometabolic disease risk. Conclusions: Replacing nearly two hours of daily sitting time with standing and reduced prolonged sitting bouts significantly improved metabolomic profiles associated with cardiometabolic risk among postmenopausal Latinas.

IntroductionCancer related cognitive decline is a common long-term side effect of cancer and its treatments among breast cancer survivors. Physical activity is a modifiable risk factor related to cognitive decline. However, existing research lacks consensus regarding the relationship between cognition and exercise as well as the impact of cancer treatments on this relationship. Baseline data from an ongoing randomized clinical trial was utilized to examine the relationship between self-reported and objectively measured cognition with physical activity. Exploratory analyses examined cancer treatments as potential moderators.MethodsBreast cancer survivors (N = 253) completed a battery of neurocognitive tests, the PROMIS Cognitive abilities questionnaire, medical charts abstracted for treatment information, and wore an ActiGraph accelerometer at the waist for 7 days. Data were analyzed using multiple linear regression models.ResultsParticipants were on average 58.5 (SD = 8.88) years old, diagnosed 3 years prior to enrollment (SD = 1.27) with 57% treated with chemotherapy and 80% receiving hormone therapy at baseline. Better self-reported cognitive ability was significantly associated with greater min of moderate to vigorous physical activity (MVPA; β = 0.070, se = 0.028, p = 0.012). There were no significant associations with any objectively measured cognitive domains. Time since diagnosis (years) was a significant moderator of MVPA and Processing Speed (β = −0.103, se = 0.043, p = 0.017). Treatment with chemotherapy and/or hormones did not significantly moderate the relationship between MVPA and any of the cognitive measures or domains.ConclusionFindings suggest that physical activity is related to self-reported cognition but not objectively measured cognition. Greater physical activity was associated with faster processing speed in participants closer in time to their cancer diagnosis. These results emphasize the need for more research to understand when cancer survivors may benefit from physical activity and what aspects of cognition may be improved.

Background Sedentary behavior is a recognized mortality risk factor. The novel and validated convolutional neural network hip accelerometer posture algorithm highly accurately classifies sitting and postural changes compared with accelerometer count cut points. We examined the prospective associations of convolutional neural network hip accelerometer posture–classified total sitting time and mean sitting bout duration with all‐cause and cardiovascular disease (CVD) death. Methods and Results Women (n=5856; mean±SD age, 79±7 years; 33% Black women, 17% Hispanic or Latina women, 50% White women) in the Women's Health Initiative Objective Physical Activity and Cardiovascular Health (OPACH) Study wore the ActiGraph GT3X+ for ~7 days from May 2012 to April 2014 and were followed through February 19, 2022 for all‐cause and CVD death. The convolutional neural network hip accelerometer posture algorithm classified total sitting time and mean sitting bout duration from GT3X+ output. Over follow‐up (median, 8.4 years; range, 0.1–9.9), there were 1733 deaths (632 from CVD). Adjusted Cox regression hazard ratios (HRs) comparing women in the highest total sitting time quartile (>696 min/d) to those in the lowest (15 minutes) to the shortest (

Abstract Background The growing amount of high dimensional biomolecular data has spawned new statistical and computational models for risk prediction and disease classification. Yet, many of these methods do not yield biologically interpretable models, despite offering high classification accuracy. An exception, the top-scoring pair (TSP) algorithm derives parameter-free, biologically interpretable single pair decision rules that are accurate and robust in disease classification. However, standard TSP methods do not accommodate covariates that could heavily influence feature selection for the top-scoring pair. Herein, we propose a covariate-adjusted TSP method, which uses residuals from a regression of features on the covariates for identifying top scoring pairs. We conduct simulations and a data application to investigate our method, and compare it to existing classifiers, LASSO and random forests. Results Our simulations found that features that were highly correlated with clinical variables had high likelihood of being selected as top scoring pairs in the standard TSP setting. However, through residualization, our covariate-adjusted TSP was able to identify new top scoring pairs, that were largely uncorrelated with clinical variables. In the data application, using patients with diabetes (n = 977) selected for metabolomic profiling in the Chronic Renal Insufficiency Cohort (CRIC) study, the standard TSP algorithm identified (valine-betaine, dimethyl-arg) as the top-scoring metabolite pair for classifying diabetic kidney disease (DKD) severity, whereas the covariate-adjusted TSP method identified the pair (pipazethate, octaethylene glycol) as top-scoring. Valine-betaine and dimethyl-arg had, respectively, ≥ 0.4 absolute correlation with urine albumin and serum creatinine, known prognosticators of DKD. Thus without covariate-adjustment the top-scoring pair largely reflected known markers of disease severity, whereas covariate-adjusted TSP uncovered features liberated from confounding, and identified independent prognostic markers of DKD severity. Furthermore, TSP-based methods achieved competitive classification accuracy in DKD to LASSO and random forests, while providing more parsimonious models. Conclusions We extended TSP-based methods to account for covariates, via a simple, easy to implement residualizing process. Our covariate-adjusted TSP method identified metabolite features, uncorrelated from clinical covariates, that discriminate DKD severity stage based on the relative ordering between two features, and thus provide insights into future studies on the order reversals in early vs advanced disease states.

BackgroundSedentary behavior among breast cancer survivors is associated with increased risk of poor physical function and worse quality of life. While moderate to vigorous physical activity can improve outcomes for cancer survivors, many are unable to engage in that intensity of physical activity. Decreasing sitting time may be a more feasible behavioral target to potentially mitigate the impact of cancer and its treatments. ObjectiveThe purpose of this study was to investigate the feasibility and preliminary impact of an intervention to reduce sitting time on changes to physical function and quality of life in breast cancer survivors, from baseline to a 3-month follow-up. MethodsFemale breast cancer survivors with self-reported difficulties with physical function received one-on-one, in-person personalized health coaching sessions aimed at reducing sitting time. At baseline and follow-up, participants wore the activPAL (thigh-worn accelerometer; PAL Technologies) for 3 months and completed physical function tests (4-Meter Walk Test, Timed Up and Go, and 30-Second Chair Stand) and Patient-Reported Outcomes Measurement Information System (PROMIS) self-reported outcomes. Changes in physical function and sedentary behavior outcomes were assessed by linear mixed models. ResultsOn average, participants (n=20) were aged 64.5 (SD 9.4) years; had a BMI of 30.4 (SD 4.5) kg/m2; and identified as Black or African American (n=3, 15%), Hispanic or Latina (n=4, 20%), and non-Hispanic White (n=14, 55%). Average time since diagnosis was 5.8 (SD 2.2) years with participants receiving chemotherapy (n=8, 40%), radiotherapy (n=18, 90%), or endocrine therapy (n=17, 85%). The intervention led to significant reductions in sitting time: activPAL average daily sitting time decreased from 645.7 (SD 72.4) to 532.7 (SD 142.1; β=–112.9; P=.001) minutes and average daily long sitting bouts (bout length ≥20 min) decreased from 468.3 (SD 94.9) to 366.9 (SD 150.4; β=–101.4; P=.002) minutes. All physical function tests had significant improvements: on average, 4-Meter Walk Test performance decreased from 4.23 (SD 0.95) to 3.61 (SD 2.53; β=–.63; P=.002) seconds, Timed Up and Go performance decreased from 10.30 (SD 3.32) to 8.84 (SD 1.58; β=–1.46; P=.003) seconds, and 30-Second Chair Stand performance increased from 9.75 (SD 2.81) to 13.20 completions (SD 2.53; β=3.45; P

Diabetic kidney disease (DKD) can lead to end-stage kidney disease (ESKD) and mortality; however, few mechanistic biomarkers are available for high-risk patients, especially those without macroalbuminuria. Urine from participants with diabetes from the Chronic Renal Insufficiency Cohort (CRIC) study, the Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes (SMART2D), and the American Indian Study determined whether urine adenine/creatinine ratio (UAdCR) could be a mechanistic biomarker for ESKD. ESKD and mortality were associated with the highest UAdCR tertile in the CRIC study and SMART2D. ESKD was associated with the highest UAdCR tertile in patients without macroalbuminuria in the CRIC study, SMART2D, and the American Indian study. Empagliflozin lowered UAdCR in nonmacroalbuminuric participants. Spatial metabolomics localized adenine to kidney pathology, and single-cell transcriptomics identified ribonucleoprotein biogenesis as a top pathway in proximal tubules of patients without macroalbuminuria, implicating mTOR. Adenine stimulated matrix in tubular cells via mTOR and stimulated mTOR in mouse kidneys. A specific inhibitor of adenine production was found to reduce kidney hypertrophy and kidney injury in diabetic mice. We propose that endogenous adenine may be a causative factor in DKD.

Abstract Background Hip-worn accelerometer cut-points have poor validity for assessing children’s sedentary time, which may partly explain the equivocal health associations shown in prior research. Improved processing/classification methods for these monitors would enrich the evidence base and inform the development of more effective public health guidelines. The present study aimed to develop and evaluate a novel computational method (CHAP-child) for classifying sedentary time from hip-worn accelerometer data. Methods Participants were 278, 8–11-year-olds recruited from nine primary schools in Melbourne, Australia with differing socioeconomic status. Participants concurrently wore a thigh-worn activPAL (ground truth) and hip-worn ActiGraph (test measure) during up to 4 seasonal assessment periods, each lasting up to 8 days. activPAL data were used to train and evaluate the CHAP-child deep learning model to classify each 10-s epoch of raw ActiGraph acceleration data as sitting or non-sitting, creating comparable information from the two monitors. CHAP-child was evaluated alongside the current practice 100 counts per minute (cpm) method for hip-worn ActiGraph monitors. Performance was tested for each 10-s epoch and for participant-season level sedentary time and bout variables (e.g., mean bout duration). Results Across participant-seasons, CHAP-child correctly classified each epoch as sitting or non-sitting relative to activPAL, with mean balanced accuracy of 87.6% (SD = 5.3%). Sit-to-stand transitions were correctly classified with mean sensitivity of 76.3% (SD = 8.3). For most participant-season level variables, CHAP-child estimates were within ± 11% (mean absolute percent error [MAPE]) of activPAL, and correlations between CHAP-child and activPAL were generally very large (> 0.80). For the current practice 100 cpm method, most MAPEs were greater than ± 30% and most correlations were small or moderate (≤ 0.60) relative to activPAL. Conclusions There was strong support for the concurrent validity of the CHAP-child classification method, which allows researchers to derive activPAL-equivalent measures of sedentary time, sit-to-stand transitions, and sedentary bout patterns from hip-worn triaxial ActiGraph data. Applying CHAP-child to existing datasets may provide greater insights into the potential impacts and influences of sedentary time in children.

Abstract Background Older adults are the least active population in the U.S. Low-income communities have fewer physical activity (PA) resources, contributing to less PA and increased chronic disease risk. This study assessed the effect of the multilevel, peer-led, Peer Empowerment Program 4 Physical Activity (PEP4PA) on moderate-to-vigorous PA (MVPA) and health outcomes, over 2 years of follow up. Methods In a cluster-randomized controlled trial, 12 senior or community centers serving low-income older adults were assigned to a PA intervention (n = 6) or usual programming (n = 6) condition. PEP4PA included self-monitoring, health coaching, group walks, social support, and community advocacy to improve walking conditions. The primary outcome was daily minutes of MVPA (7-day accelerometer). Secondary outcomes included Perceived Quality of Life (PQoL), 6-Minute Walk Test (6-MWT), blood pressure (BP), and depressive symptoms at baseline, 6, 12, 18 and 24 months. Mixed effects regression models estimated the effects on outcomes between groups over time and included random effects for repeated measures and center clustering. Effect modification by sex and income status was assessed. We calculated the incremental cost per daily minute of MVPA gained in the intervention group relative to the control group to assess cost effectiveness. Results We enrolled 476 older adults (50 + years). Participants were on average 71 years old, 76% female, 60% low income, and 38% identified as racial or ethnic minorities. Compared to the control group, intervention participants sustained roughly a 10 min/day increase in MVPA from baseline at all time points and increased mean PQoL scores from unsatisfied at baseline to satisfied at 12, 18 and 24 months. Males and higher-income groups had greater improvements in MVPA. No significant effects were observed for 6-MWT or depressive symptoms, and BP results were mixed. The incremental cost per minute MVPA gained per person was $0.25, $0.09, $0.06, and $0.05 at 6, 12, 18 and 24 months, respectively. Conclusions PEP4PA achieved increases in MVPA and PQoL in low-income older adults, over 2 years of follow up. The peer-led, community-based intervention provides a sustainable and cost-effective model to improve health behaviors in underserved, aging populations. Trial registration ClinicalTrials.gov ( NCT02405325 ) March 20, 2015.

Abstract Time spent sitting is positively correlated with endothelial dysfunction and cardiovascular disease risk. The underlying molecular mechanisms are unknown. MicroRNAs contained in extracellular vesicles (EVs) reflect cell/tissue status and mediate intercellular communication. We explored the association between sitting patterns and microRNAs isolated from endothelial cell (EC)-derived EVs. Using extant actigraphy based sitting behavior data on a cohort of 518 postmenopausal overweight/obese women, we grouped the woman as Interrupted Sitters (IS; N = 18) or Super Sitters (SS; N = 53) if they were in the shortest or longest sitting pattern quartile, respectively. The cargo microRNA in EC-EVs from the IS and SS women were compared. MicroRNA data were weighted by age, physical functioning, MVPA, device wear days, device wear time, waist circumference, and body mass index. Screening of CVD-related microRNAs demonstrated that miR-199a-5p, let-7d-5p, miR-140-5p, miR-142-3p, miR-133b level were significantly elevated in SS compared to IS groups. Group differences in let-7d-5p, miR-133b, and miR-142-3p were validated in expanded groups. Pathway enrichment analyses show that mucin-type O-glycan biosynthesis and cardiomyocyte adrenergic signaling (P

Abstract Background Sedentary behavior (SB) is linked to negative health outcomes in older adults. Most studies use summary values, e.g., total sedentary minutes/day. Diurnal timing of SB accumulation may further elucidate SB-health associations. Methods Six thousand two hundred four US women (mean age = 79 ± 7; 50% White, 34% African-American) wore accelerometers for 7-days at baseline, yielding 41,356 person-days with > 600 min/day of data. Annual follow-up assessments of health, including physical functioning, were collected from participants for 6 years. A novel two-phase clustering procedure discriminated participants’ diurnal SB patterns: phase I grouped day-level SB trajectories using longitudinal k-means; phase II determined diurnal SB patterns based on proportion of phase I trajectories using hierarchical clustering. Mixed models tested associations between SB patterns and longitudinal physical functioning, adjusted for covariates including total sedentary time. Effect modification by moderate-vigorous-physical activity (MVPA) was tested. Results Four diurnal SB patterns were identified: p1 = high-SB-throughout-the-day; p2 = moderate-SB-with-lower-morning-SB; p3 = moderate-SB-with-higher-morning-SB; p4 = low-SB-throughout-the-day. High MVPA mitigated physical functioning decline and correlated with better baseline and 6-year trajectory of physical functioning across patterns. In low MVPA, p2 had worse 6-year physical functioning decline compared to p1 and p4. In high MVPA, p2 had similar 6-year physical functioning decline compared to p1, p3, and p4. Conclusions In a large cohort of older women, diurnal SB patterns were associated with rates of physical functioning decline, independent of total sedentary time. In particular, we identified a specific diurnal SB subtype defined by less SB earlier and more SB later in the day, which had the steepest decline in physical functioning among participants with low baseline MVPA. Thus, diurnal timing of SB, complementary to total sedentary time and MVPA, may offer additional insights into associations between SB and physical health, and provide physicians with early warning of patients at high-risk of physical function decline.

BackgroundThere has been a rapid increase in the use of commercially available activity trackers, such as Fitbit, in physical activity intervention research. However, little is known about the long-term sustained use of trackers and behavior change after short-term interventions. ObjectiveThis study aims to use minute-level data collected from a Fitbit tracker for up to 2 years after the end of a randomized controlled trial to examine patterns of Fitbit use and activity over time. MethodsParticipants in this secondary data analysis were 75 female breast cancer survivors who had been enrolled in a 12-week physical activity randomized controlled trial. Participants randomized to the exercise intervention (full intervention arm) received a Fitbit One, which was worn daily throughout the 12-week intervention, and then were followed for 2 years after the intervention. Participants randomized to the waitlist arm, after completing the randomized controlled trial, received a Fitbit One and a minimal version of the exercise intervention (light intervention arm), and then were followed for 2 years after the intervention. Average and daily adherence and MVPA were compared between the 2 groups in the interventional and postinterventional periods using both linear and generalized additive mixed effects models. ResultsAdherence to wearing the Fitbit during the 12-week intervention period was significantly higher in the full intervention arm than in the light intervention arm (85% vs 60%; P

Background Current physical activity guidelines focus on volume and intensity for CVD prevention rather than common behaviors responsible for movement, including those for daily living activities. We examined the associations of a machine‐learned, accelerometer‐measured behavior termed daily life movement (DLM) with incident CVD. Methods and Results Older women (n=5416; mean age, 79±7 years; 33% Black, 17% Hispanic) in the Women’s Health Initiative OPACH (Objective Physical Activity and Cardiovascular Health) study without prior CVD wore ActiGraph GT3X+ accelerometers for up to 7 days from May 2012 to April 2014 and were followed for physician‐adjudicated incident CVD through February 28th, 2020 (n=616 events). DLM was defined as standing and moving in a confined space such as performing housework or gardening. Cox models estimated hazard ratios (HR) and 95% CI, adjusting for age, race and ethnicity, education, alcohol use, smoking, multimorbidity, self‐rated health, and physical function. Restricted cubic splines examined the linearity of the DLM‐CVD dose‐response association. We examined effect modification by age, body mass index, Reynolds Risk Score, and race and ethnicity. Adjusted HR (95% CIs) across DLM quartiles were: 1.00 (reference), 0.68 (0.55–0.84), 0.70 (0.56–0.87), and 0.57 (0.45–0.74); p‐trend0.09). There was no evidence of effect modification by age, body mass index, Reynolds Risk Score, or race and ethnicity. Conclusions Higher DLM was independently associated with a lower risk of CVD in older women. Describing the beneficial associations of physical activity in terms of common behaviors could help older adults accumulate physical activity.

PurposeThe goal of this study was to examine whether daily increased morning light exposure would maintain or improve sleep and the circadian pattern of relatively more activity in the day and less during the night in women undergoing chemotherapy for breast cancer.Patients and MethodsParticipants were 39 women with newly diagnosed breast cancer, randomized to either 30-mins of daily morning bright white light (BWL) or dim red light (DRL). Sleep/wake was measured objectively for 72-h with wrist actigraphy and subjectively with the Pittsburgh Sleep Quality Index (PSQI) prior to and during chemotherapy cycles 1 and 4. The study was registered with the National Institutes of Health ClinicalTrials.gov (Clinical Trials number: NCT00478257).ResultsResults from actigraphy suggested that compared to the DRL group, women in the BWL group had longer night-time sleep, fewer sleep disturbances during the night, and had fewer and shorter daytime naps at the end of cycle 4 of chemotherapy as well as exhibiting less activity at night and more activity during the day by the end of cycle 4. Results from PSQI indicated that components of sleep quality improved but daytime dysfunction deteriorated during cycle 4 treatment in the BWL group; meanwhile the DRL group used more sleep medications in the treatment weeks which might have led to the improved sleep quality during the recovery weeks of both cycles.ConclusionThese results suggest that bright white light therapy administered every morning on awakening may protect women undergoing chemotherapy for breast cancer from nighttime sleep and daytime wake disruption. Randomized clinical trials in larger samples are needed to confirm these findings.

Valid and reliable measures are needed to better understand the relationship between physical activity and crime. This paper provides a comprehensive psychometric evaluation of measures developed in the Safe and Fit Environments (SAFE) Study to assess a crime-PA conceptual framework. In addition to assessing the basic psychometric properties of each measure (e.g., variable distributions [item/scale level], internal consistency reliability), this study formally examined the measurement validity and invariance of measures across four age groups using confirmatory factor analysis. The sample (n = 2173) included 336 Adolescents (aged 12–17), 532 Young adults (aged 18–39), 838 Middle Age Adults, and 467 Older Adults (aged 66+). The psychometric evaluation of (sub)scales showed consistent factorial validity and internal consistency reliability across the majority of the measures and across the four age groups. Specifically, 14 of the 17 measures displayed statistically and practically significant factor loadings and internal consistency values in the overall sample and across the age groups. The pattern of correlations for each (sub)scale with other (sub)scales/indexes largely did not exhibit redundancy across measures. The findings expanded upon the test–retest reliability evaluation reported in Patch et al. (2019), and clarified key aspects of the construct validity of these indicators. The latter bodes well for potential utility of these indicators in future predictive models.

Abstract Background Physical inactivity and unhealthy diet are modifiable behaviors that lead to several cancers. Biologically, these behaviors are linked to cancer through obesity-related insulin resistance, inflammation, and oxidative stress. Individual strategies to change physical activity and diet are often short lived with limited effects. Interventions are expected to be more successful when guided by multi-level frameworks that include environmental components for supporting lifestyle changes. Understanding the role of environment in the pathways between behavior and cancer can help identify what environmental conditions are needed for individual behavioral change approaches to be successful, and better recognize how environments may be fueling underlying racial and ethnic cancer disparities. Methods This cross-sectional study was designed to select participants (n = 602 adults, 40% Hispanic, in San Diego County) from a range of neighborhoods ensuring environmental variability in walkability and food access. Biomarkers measuring cancer risk were measured with fasting blood draw including insulin resistance (fasting plasma insulin and glucose levels), systemic inflammation (levels of CRP), and oxidative stress measured from urine samples. Objective physical activity, sedentary behavior, and sleep were measured by participants wearing a GT3X+ ActiGraph on the hip and wrist. Objective measures of locations were obtained through participants wearing a Qstarz Global Positioning System (GPS) device on the waist. Dietary measures were based on a 24-h food recall collected on two days (weekday and weekend). Environmental exposure will be calculated using static measures around the home and work, and dynamic measures of mobility derived from GPS traces. Associations of environment with physical activity, obesity, diet, and biomarkers will be measured using generalized estimating equation models. Discussion Our study is the largest study of objectively measured physical activity, dietary behaviors, environmental context/exposure, and cancer-related biomarkers in a Hispanic population. It is the first to perform high quality measures of physical activity, sedentary behavior, sleep, diet and locations in which these behaviors occur in relation to cancer-associated biomarkers including insulin resistance, inflammation, impaired lipid metabolism, and oxidative stress. Results will add to the evidence-base of how behaviors and the built environment interact to influence biomarkers that increase cancer risk. Trial registration ClinicalTrials.gov NCT02094170, 03/21/2014.

Abstract Background Older adults are the least active population group. Interventions in residential settings may support a multi-level approach to behavior change. Methods In a cluster randomized control trial, 11 San Diego retirement communities were assigned to a physical activity (PA) intervention or a healthy aging attention control condition. Participants were 307 adults over 65 years old. The multilevel PA intervention was delivered with the assistance of peer leaders, who were trained older adult from the retirement communities. Intervention components included individual counseling & self-monitoring with pedometers, group education sessions, group walks, community advocacy and pedestrian community change projects. Intervention condition by time interactions were tested using generalized mixed effects regressions. The primary outcomes was accelerometer measured physical activity. Secondary outcomes were blood pressure and objectively measured physical functioning. Results Over 70% of the sample were 80 years or older. PA significantly increased in the intervention condition (56 min of moderate-vigorous PA per week; 119 min of light PA) compared with the control condition and remained significantly higher across the 12 month study. Men and participants under 84 years old benefited most from the intervention. There was a significant decrease in systolic (p

Abstract Background As the US population ages, there is an increasing need for evidence based, peer-led physical activity programs, particularly in ethnically diverse, low income senior centers where access is limited. Methods/design The Peer Empowerment Program 4 Physical Activity’ (PEP4PA) is a hybrid Type II implementation-effectiveness trial that is a peer-led physical activity (PA) intervention based on the ecological model of behavior change. The initial phase is a cluster randomized control trial randomized to either a peer-led PA intervention or usual center programming. After 18 months, the intervention sites are further randomized to continued support or no support for another 6 months. This study will be conducted at twelve senior centers in San Diego County in low income, diverse communities. In the intervention sites, 24 peer health coaches and 408 adults, aged 50 years and older, are invited to participate. Peer health coaches receive training and support and utilize a tablet computer for delivery and tracking. There are several levels of intervention. Individual components include pedometers, step goals, counseling, and feedback charts. Interpersonal components include group walks, group sharing and health tips, and monthly celebrations. Community components include review of PA resources, walkability audit, sustainability plan, and streetscape improvements. The primary outcome of interest is intensity and location of PA minutes per day, measured every 6 months by wrist and hip accelerometers and GPS devices. Secondary outcomes include blood pressure, physical, cognitive, and emotional functioning. Implementation measures include appropriateness & acceptability (perceived and actual fit), adoption & penetration (reach), fidelity (quantity & quality of intervention delivered), acceptability (satisfaction), costs, and sustainability. Discussion Using a peer led implementation strategy to deliver a multi-level community based PA program can enhance program adoption, implementation, and sustainment. Trial registration ClinicalTrials.gov, USA ( NCT02405325 ). Date of registration, March 20, 2015. This website also contains all items from the World Health Organization Trial Registration Data Set.

Background Sedentary behavior is pervasive, especially in older adults, and is associated with cardiometabolic disease and mortality. Relationships between cardiometabolic biomarkers and sitting time are unexplored in older women, as are possible ethnic differences. Methods and Results Ethnic differences in sitting behavior and associations with cardiometabolic risk were explored in overweight/obese postmenopausal women (n=518; mean±SD age 63±6 years; mean body mass index 31.4±4.8 kg/m2). Accelerometer data were processed using validated machine‐learned algorithms to measure total daily sitting time and mean sitting bout duration (an indicator of sitting behavior pattern). Multivariable linear regression was used to compare sitting among Hispanic women (n=102) and non‐Hispanic women (n=416) and tested associations with cardiometabolic risk biomarkers. Hispanic women sat, on average, 50.3 minutes less/day than non‐Hispanic women (P

The incidence of type 2 diabetes is increasing more rapidly in adolescents than in any other age group. We identified and compared metabolite signatures in obese children with type 2 diabetes (T2D), obese children without diabetes (OB), and healthy, age- and gender-matched normal weight controls (NW) by measuring 273 analytes in fasting plasma and 24-hour urine samples from 90 subjects by targeted LC-MS/MS. Diabetic subjects were within 2 years of diagnosis in an attempt to capture early-stage disease prior to declining renal function. We found 22 urine metabolites that were uniquely associated with T2D when compared to OB and NW groups. The metabolites most significantly elevated in T2D youth included members of the betaine pathway, nucleic acid metabolism, and branched-chain amino acids (BCAAs) and their catabolites. Notably, the metabolite pattern in OB and T2D groups differed between urine and plasma, suggesting that urinary BCAAs and their intermediates behaved as a more specific biomarker for T2D, while plasma BCAAs associated with the obese, insulin resistant state independent of diabetes status. Correlative analysis of metabolites in the T2D signature indicated that betaine metabolites, BCAAs, and aromatic amino acids were associated with hyperglycemia, but BCAA acylglycine derivatives and nucleic acid metabolites were linked to insulin resistance. Of major interest, we found that urine levels of succinylaminoimidazole carboxamide riboside (SAICA-riboside) were increased in diabetic youth, identifying urine SAICA-riboside as a potential biomarker for T2D.

Acute kidney injury (AKI) is defined as a rapid decline in kidney function. The associated syndromes may lead to increased morbidity and mortality, but its early detection remains difficult. Using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS), we analyzed the urinary metabolomic profile of patients admitted to the intensive care unit (ICU) after invasive surgery. Urine samples were collected at six time points: before surgery, at ICU admission and 6, 12, 24 and 48 h after. First, urine samples from 61 initial patients (non-AKI: 23, mild AKI: 24, severe AKI: 14) were measured, followed by the measurement of urine samples from 60 additional patients (non-AKI: 40, mild AKI: 20). Glycine and ethanolamine were decreased in patients with AKI compared with non-AKI patients at 6–24 h in the two groups. The linear statistical model constructed at each time point by machine learning achieved the best performance at 24 h (median AUC, area under the curve: 89%, cross-validated) for the 1st group. When cross-validated between the two groups, the AUC showed the best value of 70% at 12 h. These results identified metabolites and time points that show patterns specific to subjects who develop AKI, paving the way for the development of better biomarkers.

ObjectivesIndependently, physical activity (PA), sedentary behavior (SB), and sleep are related to the development and progression of chronic diseases. Less is known about how rest-activity behaviors cluster within individuals and how rest-activity behavior profiles relate to health. In this study we aimed to investigate if adult women cluster into profiles based on how they accumulate rest-activity behavior (including accelerometer-measured PA, SB, and sleep), and if participant characteristics and health outcomes differ by profile membership.MethodsA convenience sample of 372 women (mean age 55.38 + 10.16) were recruited from four US cities. Participants wore ActiGraph GT3X+ accelerometers on the hip and wrist for a week. Total daily minutes in moderate-to-vigorous PA (MVPA) and percentage of wear-time spent in SB was estimated from the hip device. Total sleep time (hours/minutes) and sleep efficiency (% of in bed time asleep) were estimated from the wrist device. Latent profile analysis (LPA) was performed to identify clusters of participants based on accumulation of the four rest-activity variables. Adjusted ANOVAs were conducted to explore differences in demographic characteristics and health outcomes across profiles.ResultsRest-activity variables clustered to form five behavior profiles: Moderately Active Poor Sleepers (7%), Highly Actives (9%), Inactives (41%), Moderately Actives (28%), and Actives (15%). The Moderately Active Poor Sleepers (profile 1) had the lowest proportion of whites (35% vs 78-91%, p < .001) and college graduates (28% vs 68-90%, p = .004). Health outcomes did not vary significantly across all rest-activity profiles.ConclusionsIn this sample, women clustered within daily rest-activity behavior profiles. Identifying 24-hour behavior profiles can inform intervention population targets and innovative behavioral goals of multiple health behavior interventions.

Obesity and its impact on health is a multifaceted phenomenon encompassing many factors, including demographics, environment, lifestyle, and psychosocial functioning. A systems science approach, investigating these many influences, is needed to capture the complexity and multidimensionality of obesity prevention to improve health. Leveraging baseline data from a unique clinical cohort comprising 333 postmenopausal overweight or obese breast cancer survivors participating in a weight-loss trial, we applied Bayesian networks, a machine learning approach, to infer interrelationships between lifestyle factors (e.g., sleep, physical activity), body mass index (BMI), and health outcomes (biomarkers and self-reported quality of life metrics). We used bootstrap resampling to assess network stability and accuracy, and Bayesian information criteria (BIC) to compare networks. Our results identified important behavioral subnetworks. BMI was the primary pathway linking behavioral factors to glucose regulation and inflammatory markers; the BMI-biomarker link was reproduced in 100% of resampled networks. Sleep quality was a hub impacting mental quality of life and physical health with > 95% resampling reproducibility. Omission of the BMI or sleep links significantly degraded the fit of the networks. Our findings suggest potential mechanistic pathways and useful intervention targets for future trials. Using our models, we can make quantitative predictions about health impacts that would result from targeted, weight loss and/or sleep improvement interventions. Importantly, this work highlights the utility of Bayesian networks in health behaviors research.

Physical activity and time spent outdoors may be important non-pharmacological approaches to improve sleep quality and duration (or sleep patterns) but there is little empirical research evaluating the two simultaneously. The current study assesses the role of physical activity and time outdoors in predicting sleep health by using objective measurement of the three variables. A convenience sample of 360 adult women (mean age = 55.38 ±9.89 years; mean body mass index = 27.74 ±6.12) was recruited from different regions of the U.S. Participants wore a Global Positioning System device and ActiGraph GT3X+ accelerometers on the hip for 7 days and on the wrist for 7 days and 7 nights to assess total time and time of day spent outdoors, total minutes in moderate-to-vigorous physical activity per day, and 4 measures of sleep health, respectively. A generalized mixed-effects model was used to assess temporal associations between moderate-to-vigorous physical activity, outdoor time, and sleep at the daily level (days = 1931) within individuals. There was a significant interaction (p = 0.04) between moderate-to-vigorous physical activity and time spent outdoors in predicting total sleep time but not for predicting sleep efficiency. Increasing time outdoors in the afternoon (versus morning) predicted lower sleep efficiency, but had no effect on total sleep time. Time spent outdoors and the time of day spent outdoors may be important moderators in assessing the relation between physical activity and sleep. More research is needed in larger populations using experimental designs.

Prolonged sitting is associated with cardiometabolic and vascular disease. Despite emerging evidence regarding the acute health benefits of interrupting prolonged sitting time, the effectiveness of different modalities in older adults (who sit the most) is unclear.In preparation for a future randomized controlled trial, we enrolled 10 sedentary, overweight or obese, postmenopausal women (mean age 66 years ±9; mean body mass index 30.6 kg/m2 ±4.2) in a 4-condition, 4-period crossover feasibility pilot study in San Diego to test 3 different sitting interruption modalities designed to improve glucoregulatory and vascular outcomes compared to a prolonged sitting control condition. The interruption modalities included: a) 2 minutes standing every 20 minutes; b) 2 minutes walking every hour; and c) 10 minutes standing every hour. During each 5-hr condition, participants consumed two identical, standardized meals. Blood samples, blood pressure, and heart rate were collected every 30 minutes. Endothelial function of the superficial femoral artery was measured at baseline and end of each 5-hr condition using flow-mediated dilation (FMD). Participants completed each condition on separate days, in randomized order. This feasibility pilot study was not powered to detect statistically significant differences in the various outcomes, however, analytic methods (mixed models) were used to test statistical significance within the small sample size.Nine participants completed all 4 study visits, one participant completed 3 study visits and then was lost to follow up. Net incremental area under the curve (iAUC) values for postprandial plasma glucose and insulin during the 5-hr sitting interruption conditions were not significantly different compared to the control condition. Exploratory analyses revealed that the 2-minute standing every 20 minutes and the 2-minute walking every hour conditions were associated with a significantly lower glycemic response to the second meal compared to the first meal (i.e., condition-matched 2-hour post-lunch glucose iAUC was lower than 2-hour post-breakfast glucose iAUC) that withstood Bonferroni correction (p = 0.0024 and p = 0.0084, respectively). Using allometrically scaled data, the 10-minute standing every hour condition resulted in an improved FMD response, which was significantly greater than the control condition after Bonferroni correction (p = 0.0033).This study suggests that brief interruptions in prolonged sitting time have modality-specific glucoregulatory and vascular benefits and are feasible in an older adult population. Larger laboratory and real-world intervention studies of pragmatic and effective methods to change sitting habits are needed.ClinicalTrials.gov NCT02743286.

The main purpose of the present study was to assess the impact of global positioning system (GPS) signal lapse on physical activity analyses, discover any existing associations between missing GPS data and environmental and demographics attributes, and to determine whether imputation is an accurate and viable method for correcting GPS data loss. Accelerometer and GPS data of 782 participants from 8 studies were pooled to represent a range of lifestyles and interactions with the built environment. Periods of GPS signal lapse were identified and extracted. Generalised linear mixed models were run with the number of lapses and the length of lapses as outcomes. The signal lapses were imputed using a simple ruleset, and imputation was validated against person-worn camera imagery. A final generalised linear mixed model was used to identify the difference between the amount of GPS minutes pre- and post-imputation for the activity categories of sedentary, light, and moderate-to-vigorous physical activity. Over 17% of the dataset was comprised of GPS data lapses. No strong associations were found between increasing lapse length and number of lapses and the demographic and built environment variables. A significant difference was found between the pre- and postimputation minutes for each activity category. No demographic or environmental bias was found for length or number of lapses, but imputation of GPS data may make a significant difference for inclusion of physical activity data that occurred during a lapse. Imputing GPS data lapses is a viable technique for returning spatial context to accelerometer data and improving the completeness of the dataset.

BackgroundOptimal macronutrient distribution of weight loss diets has not been established. The distribution of energy from carbohydrate and fat has been observed to promote differential plasma lipid responses in previous weight loss studies, and insulin resistance status may interact with diet composition and affect weight loss and lipid responses. Methods and ResultsOverweight and obese women (n=245) were enrolled in a 1‐year behavioral weight loss intervention and randomly assigned to 1 of 3 study groups: a lower fat (20% energy), higher carbohydrate (65% energy) diet; a lower carbohydrate (45% energy), higher fat (35% energy) diet; or a walnut‐rich, higher fat (35% energy), lower carbohydrate (45% energy) diet. Blood samples and data available from 213 women at baseline and at 6 months were the focus of this analysis. Triglycerides, total cholesterol, and high‐ and low‐density lipoprotein cholesterol were quantified and compared between and within groups. Triglycerides decreased in all study arms at 6 months (P

Emerging evidence suggests that there is interplay between the frequency and circadian timing of eating and metabolic health. We examined the associations of eating frequency and timing with metabolic and inflammatory biomarkers putatively associated with breast cancer risk in women participating in the National Health and Nutrition Examination 2009-2010 Survey. Eating frequency and timing variables were calculated from 24-hour food records and included (1) proportion of calories consumed in the evening (5 pm-midnight), (2) number of eating episodes per day, and (3) nighttime fasting duration. Linear regression models examined each eating frequency and timing exposure variable with C-reactive protein (CRP) concentrations and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Each 10 percent increase in the proportion of calories consumed in the evening was associated with a 3 percent increase in CRP. Conversely, eating one additional meal or snack per day was associated with an 8 percent reduction in CRP. There was a significant interaction between proportion of calories consumed in the evening and fasting duration with CRP (p = 0.02). A longer nighttime fasting duration was associated with an 8 percent lower CRP only among women who ate less than 30% of their total daily calories in the evening (p = 0.01). None of the eating frequency and timing variables were significantly associated with HOMA-IR. These findings suggest that eating more frequently, reducing evening energy intake, and fasting for longer nightly intervals may lower systemic inflammation and subsequently reduce breast cancer risk. Randomized trials are needed to validate these associations.

Total sedentary time varies across population groups with important health consequences. Patterns of sedentary time accumulation may vary and have differential health risks. The purpose of this study is to describe sedentary patterns of older adults living in retirement communities and illustrate gender and age differences in those patterns.Baseline accelerometer data from 307 men and women (mean age = 84±6 years) who wore ActiGraph GT3X+ accelerometers for ≥ 4 days as part of a physical activity intervention were classified into bouts of sedentary time (