Corby K. Martin, Ph.D. - US grants

The research proposed in this Career Development Award consists of two projects. During Project 1, the accuracy of measuring spontaneous physical activity (SPA) and activity energy expenditure (AEE) with the Intelligent Device for Energy Expenditure and Activity (IDEEA[unreadable];MiniSun LLC, Fresno, CA) will be tested. SPA consists of the energy expended with bodily movement (e.g., fidgeting, changing posture) and it is measured in the metabolic chamber. AEE consists of the energy expended in all activities and it is measured with doubly labeled water (DLW). The IDEEA[unreadable] records bodily movement and energy expenditure through sensors that are attached to the body. The accuracy of measuring SPA and AEE with the IDEEA[unreadable] will be tested in a group of lean and overweight adults who spend 24 hours in a metabolic chamber and whose AEE is measured with DLW for a one-week free-living period. The accuracy of the IDEEA[unreadable] will be tested with equivalence tests and Bland-Altman regression analysis will be used to test if bias associated with the IDEEA[unreadable] is consistent across different levels of energy expenditure. The ability of SPA and AEE to predict weight loss during a two-year calorie restriction trial will also be tested with regression analysis, and moderating and mediating effects of gender and activity temperament will be tested. In addition, the ability of the amount of time spent engaging in, and the'energy costs of, active and sedentary behaviors at baseline to predict weight loss will be tested. During Project 2, two data analytic techniques, cluster analysis and taxometric analysis, will be utilized to test for clusters and distinct groups of people (taxons) whose metabolic or behavioral/psycho social profile predisposes them to weight gain and obesity. Project 2 will rely on two sources of data: 1) an archival database of metabolic variables from Pima Indians and Caucasians, and 2) data from a two-year weight loss trial that includes both metabolic and behavioral/psychosocial variables. The ability of cluster and taxometric analyses to identify clusters or taxons of people who are predisposed to obesity will be tested by determining if these clusters or taxons predict weight loss during the two-year weight loss trial. Furthermore, these analyses represent a thorough test for the presence of a "thrifty metabolic phenotype." The research outlined in this Career Development Award will provide a foundation for an independent research career. Moreover, this research will provide important information about the pathogenesis of obesity and whether distinct groups of people are predisposed to obesity, or if they differ from lean individuals on dimensional variables. The results of this study will provide important information on targets for interventions designed to alter energy balance and promote weight loss or weight gain prevention.

DESCRIPTION (provided by applicant): The prevalence of obesity is increasing worldwide and there is a strong consensus that weight gain and obesity are the consequence of a positive energy balance, which occurs when more energy is ingested than expended. Energy intake (food intake) is one of the primary culprits of weight gain, yet few accurate methods exist to measure food intake in people's natural environment or free-living conditions. Consequently, it is difficult for scientists to study food intake, energy balance, weight gain, and obesity. Additionally, it is difficult for people who wish to manage their weight to learn how to modify energy balance, since their ability to manage energy balance is hindered by inaccurate information about energy intake. Food records or food diaries are frequently used to measure energy intake, but they have been found to be inaccurate. When completing a food record, people record the types and amounts of the foods that they eat on pen-and-paper forms. The "gold standard" for measuring energy intake relies on the doubly labeled water method, but this method is costly and not available to most researchers and clinicians. The doubly labeled water method also does not provide information about the types of foods being eaten and the macronutrient composition of the diet. Therefore, this method provides little information about the nutritional adequacy of the diet. Digital photography of foods, a method that has been found to accurately measure energy intake in naturalistic settings (e.g., cafeterias), might also have promise in improving estimates of food intake in free-living individuals. When using this method, the plate of foods selected by an individual is photographed with a digital camera before the meal and plate waste is photographed after the meal. Reference or standard portions of known quantities of the foods are also photographed. In the laboratory, trained judges (registered dietitians) use these photographs to estimate the portion size of food selection and plate waste by comparing these photographs to the photograph of a standard portion. These estimates are entered into a computer application that calculates food intake (food intake = food selection minus plate waste). A series of pilot studies has found that this method can be altered and used in free-living conditions. The purpose of this study is to develop and test innovative technology that will acilitate the collection of accurate energy intake data in free-living humans sing the digital photography method. Participants will take photographs of their food selection and plate waste sing cell phones and these data will be transferred to the researchers'database over the cellular network in ear "real-time." A semi-automated computer application will be developed to automatically identify the foods in these pictures and estimate the amount of food eaten based on he pictures. During the proposed project, this computer application will be developed and the reliability and validity (accuracy) of the method for estimating good intake will be tested in laboratory and free-living conditions. This research promises to significantly advance the study of energy balance and provide a useful tool to clinicians for measuring energy intake.

DESCRIPTION (provided by applicant): A large proportion of the adult population in the United States qualifies for weight loss treatment based on the NIH treatment recommendations, but traditional clinic-based weight loss treatments have a number of limitations. For example, access to healthcare facilities is limited among people living in rural communities and people of low socioeconomic status, yet a disproportionate number of these people would benefit from services. Internet-based weight loss interventions have been used to deliver services to these populations, but these "e-Health" interventions suffer from a number of limitations and produce only modest weight loss. The limitations associated with internet-based interventions include decreased use of the internet application over time;patients must logon to the internet to receive treatment recommendations, yet few patients regularly logon to the application and this negatively affects treatment outcome. An additional limitation is the quality of self-reported food intake, exercise, and body weight data that participants enter into the internet application or report to their online counselor. Self-reported data are associated with error and accurate data are needed to formulate effective treatment recommendations for participants. Lastly, most applications rely on asynchronous communications between the patient and the counselor, and patients do not always receive personalized treatment recommendations in a reasonable amount of time (1 to 3 days), which limits the extent to which the recommendations result in behavior change and weight loss. The purpose of the proposed pilot and feasibility project is to test the efficacy of the Remote Intervention for Diet and Exercise (RIDE) e-Health application at promoting weight loss compared to a control condition. The RIDE e-Health application addresses the limitations of internet-based interventions that are noted above. The application relies on novel technology to collect near real-time food intake, body weight, and exercise data from participants while they reside in their free-living environments. These data are transmitted to the researchers in near real-time: food intake data are collected and transmitted with camera and Bluetooth-enabled cell phones using the Remote Food Photography method that was developed by this laboratory, body weight data is automatically transmitted daily from a bathroom scale using the same phones, and accelerometry is used to collect exercise data that is transmitted via the internet. These data are analyzed and personalized treatment recommendations are sent to the participant in a timely manner, e.g., every 1 to 3 days, using the cell phones. The RIDE e-Health application was developed based on learning and behavioral theory to maximize behavior change and weight loss. The findings of this study will have significant implications for the affordable delivery of effective weight management interventions to patients with limited access to health care. PUBLIC HEALTH RELEVANCE: The proposed research will provide important information on the efficacy of the Remote Intervention for Diet and Exercise (RIDE) e-Health application at promoting weight loss. The findings will have significant implications for the affordable delivery of weight management services to people who have limited access to health care, including people who live in rural communities and those with financial limitations. A disproportionate number of these individuals would benefit from weight management services, but a number of barriers limit access to services. The RIDE e-Health application overcomes many of these barriers, as well as the limitations of previous e-Health weight loss interventions.

DESCRIPTION (provided by applicant): High body weight is associated with increased risk for hypertension, dyslipidemia, inflammation, metabolic syndrome, stroke, and coronary heart disease. While exercise is commonly cited as an important tool for weight reduction, numerous studies have demonstrated that: 1) exercise training without a dietary intervention results in far less weight loss than expected given the expended calories and this is most evident when the exercise dose is large (e 60 minutes per day), and 2) the weight loss response to exercise is very heterogeneous. Nevertheless, most weight management guidelines recommend an hour or more a day of exercise both for promoting weight loss and preventing weight regain after loss. There is clearly a need to identify the mechanisms responsible for the failure of exercise to produce substantial weight loss in most but not all individuals, as having a better understanding of the mechanisms responsible for this phenomenon is critical to developing strategies to counter it. The leading mechanisms include exercise-induced increases in energy intake, decreases in resting metabolic rate (adjusted for change in body mass), and decreases in non- exercise activity levels. The purpose of the E-MECHANIC Trial is to compare the effect of two doses of exercise on energy intake and body weight. The exercise doses will reflect current recommendations for: 1) general health (~800- 1000 kcal/week), and 2) weight loss and maintenance of weight loss (~2000 to 2500 kcal/week). The exercise groups will not be provided with a dietary intervention, and the study also includes a non-exercise control group. The primary outcome variables are energy intake and the discrepancy between expected weight loss and observed weight loss (Wt. Lossdif). Energy intake will be measured using two state-of-the-art methods: doubly labeled water and laboratory-based food intake tests. Energy intake was chosen as the primary outcome variable and the most likely compensatory mechanism that limits exercise-induced weight loss, but change in metabolism (resting metabolic rate adjusted for change in body composition) and activity levels (excluding structured exercise) will also be evaluated as possible compensatory mechanisms and secondary outcome variables. Lastly, in an effort to guide the development of interventions to combat compensation, we will behaviorally phenotype participants to characterize those who do and do not compensate by increasing energy intake. The results of the study will provide important information for health and weight loss recommendations, and identify ways to counter compensatory mechanisms that limit exercise-induced weight loss. PUBLIC HEALTH RELEVANCE: Excess body weight is a significant risk factor for cardiovascular disease. Exercise is recommended for weight reduction, yet exercise training without a dietary intervention results in far less weight loss than expected given the expended calories and this is most evident when the exercise dose is large (e 60 minutes per day). In addition, the weight loss response to exercise is very heterogeneous. There is a need to identify the mechanisms responsible for the failure of exercise to produce substantial weight loss in most but not all individuals, as having a better understanding of the mechanisms responsible for this phenomenon is critical to developing strategies to counter it. The purpose of the proposed research is to identify the mechanisms responsible for the failure of exercise to promote the expected amount of weight loss. Specifically, the study will determine if exercise results in increased energy intake, decreased resting metabolic rate (adjusted for change in body mass), and/or decreased non-exercise activity levels, which compensate for the energy deficit caused by exercise and limit weight loss. The results of the study will provide important information for weight loss recommendations and the development of interventions to combat compensation.

DESCRIPTION (provided by applicant): Excess weight gain during pregnancy leads to significant long-term metabolic morbidities in mothers and their offspring. More than 50% of reproductive age women in the US exceed weight gain guidelines during pregnancy as recommended by the Institute of Medicine. Lifestyle modification programs targeting healthy eating and regular physical activity are successful in controlling weight gain as well as preventing obesity related co-morbidities in other at risk populations. However few lifestyle intervention studies have been conducted in pregnant women to manage gestational weight gain and none were successful in helping women adhere to the guidelines. Although pregnant women are believed to be a highly motivated population for accepting behavior change, they face several barriers to traditional in-person clinic weight management programs. We have successfully implemented lifestyle interventions for weight management through Tele-health technologies (Smartphone) to overweight and obese individuals and these are readily adaptable to pregnant women. Application of Tele-health technologies to pregnant women may therefore successfully address these barriers and facilitate appropriate weight gain during pregnancy. The objective of this study Expecting Success: Personalized weight management during pregnancy is to implement a personalized gestational weight management program to overweight and obese pregnant women that focuses on healthy eating and achieving National physical activity recommendations. 300 primiparous overweight and obese women will be randomly assigned to receive either usual care or a personalized lifestyle program for weight management delivered in-person or remotely via a Smartphone. The lifestyle program involves weekly contact with counselors from week 13 of gestation until delivery. Clinical assessments will be obtained throughout pregnancy and in the mother and offspring during the first year postpartum. This study is significant because it seeks to prevent excess weight gain during pregnancy, a major health problem for pregnant women and their offspring. If successful, our Smartphone approach will provide a novel, efficacious and scalable intervention for weight management in pregnant women.

DESCRIPTION (provided by applicant): The prevalence of overweight and obesity among children and adolescents is increasing. Alarmingly, overweight and obese children are experiencing weight-related health problems before adulthood, such as type 2 diabetes mellitus. Weight gain and obesity are the consequence of a positive energy balance, which occurs when more energy is ingested than expended, and energy intake is an important predictor of weight gain. The types of foods that children and adolescents eat also affect health. Children and adolescents consume over 500 kcal/day of low-nutrient, energy dense foods, and nutritional deficiency can occur even in the presence of overconsumption of energy. For example, obese children have higher rates of iron deficiency. Accurate methods to measure the food intake of children and adolescents are needed to facilitate research and interventions to promote healthy eating and weight management. Existing methods, such as self- report (e.g., food records), are associated with significant participant and, with younger children, caregiver burden. Moreover, these methods produce inaccurate (low) estimates of food intake, particularly for people of higher body mass and adolescents. A large source of error when using these methods is due to participants' poor estimation of portion size. Hence, there is a need to develop and validate methods to estimate the food intake of children, namely adolescents that do not rely on the participant's ability to accurately estimate portion size. Our group developed the Remote Food Photography Method (RFPM) for measuring the food intake of adults in near real-time, and the validity data are positive. The RFPM underestimated energy intake by less than 7% over 7 days in free-living conditions when compared to the gold standard, doubly labeled water. When utilizing the RFPM, participants use a Smartphone to take pictures of their food selection and plate waste. These pictures are immediately sent to the researchers via a wireless network. Participants receive automated prompts (emails) on the Smartphone that are consistent with Ecological Momentary Assessment (EMA) methodology reminding them to take pictures of their foods. Computer applications were developed to manage EMA methods and to automatically identify foods and estimate food intake using computer imaging algorithms. Data are collected and analyzed quickly and efficiently, allowing near real-time food intake measurement. During the proposed research, the RFPM will be modified to measure the food intake of adolescents. The validity of the RFPM will then be compared to the validity of pen-and-paper food records. Following modification of the RFPM and pilot testing with 4 adolescents, the reliability and validity of the RFPM and food records will then be tested in a sample of 64 adolescents (age 12-18 years). In a balanced order across participants, the RFPM will be used during one week, and food records will be used during another week. Food intake estimated with both methods will be compared to three gold standards: 1) energy intake measured by doubly labeled water (DLW) in free-living conditions, 2) food intake (energy and nutrient intake) measured during lunch in a school cafeteria, and 3) food intake measured during a laboratory-based test meal. User satisfaction and burden also will be compared between methods (RFPM and food records), and a cost- effectiveness analysis will determine if and under what conditions one method is more cost-effective than the other. We will also test if the RFPM's validity is associated with levels of energy intake.

DESCRIPTION (provided by applicant): The prevalence of overweight and obesity among children and adolescents is increasing. Alarmingly, overweight and obese children are experiencing weight-related health problems before adulthood, such as type 2 diabetes mellitus. Weight gain and obesity are the consequence of a positive energy balance, which occurs when more energy is ingested than expended, and energy intake is an important predictor of weight gain. The types of foods that children and adolescents eat also affect health. Children and adolescents consume over 500 kcal/day of low-nutrient, energy dense foods, and nutritional deficiency can occur even in the presence of overconsumption of energy. For example, obese children have higher rates of iron deficiency. Accurate methods to measure the food intake of children and adolescents are needed to facilitate research and interventions to promote healthy eating and weight management. Existing methods, such as self- report (e.g., food records), are associated with significant participant and, with younger children, caregiver burden. Moreover, these methods produce inaccurate (low) estimates of food intake, particularly for people of higher body mass and adolescents. A large source of error when using these methods is due to participants' poor estimation of portion size. Hence, there is a need to develop and validate methods to estimate the food intake of children, namely adolescents that do not rely on the participant's ability to accurately estimate portion size. Our group developed the Remote Food Photography Method (RFPM) for measuring the food intake of adults in near real-time, and the validity data are positive. The RFPM underestimated energy intake by less than 7% over 7 days in free-living conditions when compared to the gold standard, doubly labeled water. When utilizing the RFPM, participants use a Smartphone to take pictures of their food selection and plate waste. These pictures are immediately sent to the researchers via a wireless network. Participants receive automated prompts (emails) on the Smartphone that are consistent with Ecological Momentary Assessment (EMA) methodology reminding them to take pictures of their foods. Computer applications were developed to manage EMA methods and to automatically identify foods and estimate food intake using computer imaging algorithms. Data are collected and analyzed quickly and efficiently, allowing near real-time food intake measurement. During the proposed research, the RFPM will be modified to measure the food intake of adolescents. The validity of the RFPM will then be compared to the validity of pen-and-paper food records. Following modification of the RFPM and pilot testing with 4 adolescents, the reliability and validity of the RFPM and food records will then be tested in a sample of 64 adolescents (age 12-18 years). In a balanced order across participants, the RFPM will be used during one week, and food records will be used during another week. Food intake estimated with both methods will be compared to three gold standards: 1) energy intake measured by doubly labeled water (DLW) in free-living conditions, 2) food intake (energy and nutrient intake) measured during lunch in a school cafeteria, and 3) food intake measured during a laboratory-based test meal. User satisfaction and burden also will be compared between methods (RFPM and food records), and a cost- effectiveness analysis will determine if and under what conditions one method is more cost-effective than the other. We will also test if the RFPM's validity is associated with levels of energy intake.

? DESCRIPTION (provided by applicant): WorkACTIVE-P is a high quality exploratory/developmental R21 preliminary outcome evaluation of an innovative multi-component intervention designed to raise energy expenditure and re-balance the disrupted energy balance equation of sedentary workplaces with a target of reducing workers' abdominal obesity. The multi-component intervention uses behavior change theory and technological advances to promote and track walking more and using a pedal desk workstation alternative in the sedentary workplace. This R21 addresses health risks associated with occupational sedentary behavior, specifically abdominal obesity, in Services Industry Sector and the Total Worker Health cross-sector of the National Occupational Research Agenda (NORA). WorkACTIVE-P is a continued exemplary effort of Research to Practice (r2p), building on our prior work with the Service Industry to implement and evaluate treadmill desks as workstation alternatives. Over the course of a 2-year period we will work closely with our Services Industry partner to identify, recruit, and randomly assign 40 low active (< 7,500 steps/day), overweight/obese sedentary full-time workers, 40-64 years of age, with abdominal obesity defined by waist circumference and at least one additional component of the metabolic syndrome (dyslipidemia, elevated blood pressure, and/or impaired fasting glucose), to a 3-month-long controlled trial with two arms: 1) a combined electronic behavior support program of walk more and pedal desk (WMPD, n=20), which, in addition to provision of a dedicated pedal desk in individual worker's office space, participants are supported to increase daily walking by at least 3000 steps/day; and 2) a usual working condition group (CON, n=20). The primary outcome is change in abdominal obesity operationalized as MRI-determined visceral adipose tissue (VAT). Secondary outcomes include changes in body weight, total adipose tissue, subcutaneous adipose tissue, blood pressure, blood lipids, fasting glucose and insulin, [HbA1c], free-living accelerometer-determined walking (steps/day and cadence), time spent in sedentary behavior, exercise (time spent at moderate-to-vigorous physical activity), and dietary intake. We will electronically track daily steps data for WMPD participants and also duration of use and cadence (rpm) of pedal desks. Layering a step-counting intervention on top of a pedal desk intervention permits a clear evaluation of their separate and combined dose-response effects. Daily electronic tracking of pedal desk use and steps/day via automatic internet-based software enables continuous tracking of both behaviors for tailored feedback, behavioral shaping, and evaluation purposes. The expected outputs and outcomes of WorkACTIVE-P include providing clear feasibility and preliminary effectiveness evidence for a combination of practical technology-supported products and programs for Service Industry employers and workers interested in addressing health risk exposures (and related health care costs) associated with occupational sedentary behavior.

C. Abstract (Human Phenotyping) The Human Phenotyping Core (HPC) and its two sub-cores (the Energy Balance and Behavioral sub-cores) directly support the research of NORC members by providing innovative clinical and intervention services to phenotype humans in mechanistic, clinical, and translational studies. The services o f t h e Energy Balance sub-core include methods to quantify body composition, energy expenditure, carbohydrate metabolism, and cardiorespiratory fitness. The services of the Behavioral sub-core include behavioral, cognitive, and psychological assessments; measurement of food intake in laboratory and free-living conditions; design and delivery of behavioral change interventions; and assessment of activity and sedentary behavior in free- living conditions. Over the first 10 years of NORC funding, the HPC: a) provided comprehensive services for human phenotyping in clinical research studies, b) developed and validated innovative phenotyping methods and interventions, c) established quality control procedures, and d) built a growing base of HPC users. In years 1-5, the majority of the HPC's effort focused on adult phenotyping. Over years 6-10, however, the HPC transitioned to include g reater emphasis on novel imaging techniques and methods to phenotype mothers, infants, and children. This is consistent with the NORC's theme of nutrition, obesity, and metabolic health through the lifespan. At each period of the lifespan, we conduct research to understand the mechanisms, prevention, and treatment of obesity; and our research focus areas have evolved to include a) maternal and infant nutritional status, b) pediatric and adulthood obesity, and c) nutritional status in older age to preserve physical and cognitive functionality. The Aims of the current renewal application to fund years 11-15 are: 1) provide members with a comprehensive suite of innovative energy balance and behavioral services to ongoing funded and collaborative research projects to enable the characterization of human subjects in clinical and translational research studies, and continue to expand services to phenotype individuals at specific stages of life, such as pregnancy and infancy, 2) provide specialist expertise to support clinical and translational research on nutrition, obesity and metabolic health at different stages of life, and continue to enhance our quality control procedures to provide efficient and high quality services, 3) sustain a human tissue bio-repository, including metabolic tissues (muscle, adipose) and biospecimens that are needed for ongoing fundamental and translational studies of nutrition, obesity, and metabolic health relative to pregnancy (placenta, cord blood), infancy (breast milk), and childhood, 4) expand imaging capabilities including food-intake-relevant fMRI, enhanced body composition and metabolism, and rodent imaging to increase the power and quality of our research results, and 5) proactively facilitate increased utilization of the core services; integrate core services with pilot and feasibility studies; and continually monitor and improve utilization and priorities for core services. These aims build upon the previous 10 years of work and bolster support for NORC members' research.

? DESCRIPTION (provided by applicant): WorkACTIVE-P is a high quality exploratory/developmental R21 preliminary outcome evaluation of an innovative multi-component intervention designed to raise energy expenditure and re-balance the disrupted energy balance equation of sedentary workplaces with a target of reducing workers' abdominal obesity. The multi-component intervention uses behavior change theory and technological advances to promote and track walking more and using a pedal desk workstation alternative in the sedentary workplace. This R21 addresses health risks associated with occupational sedentary behavior, specifically abdominal obesity, in Services Industry Sector and the Total Worker Health cross-sector of the National Occupational Research Agenda (NORA). WorkACTIVE-P is a continued exemplary effort of Research to Practice (r2p), building on our prior work with the Service Industry to implement and evaluate treadmill desks as workstation alternatives. Over the course of a 2-year period we will work closely with our Services Industry partner to identify, recruit, and randomly assign 40 low active (< 7,500 steps/day), overweight/obese sedentary full-time workers, 40-64 years of age, with abdominal obesity defined by waist circumference and at least one additional component of the metabolic syndrome (dyslipidemia, elevated blood pressure, and/or impaired fasting glucose), to a 3-month-long controlled trial with two arms: 1) a combined electronic behavior support program of walk more and pedal desk (WMPD, n=20), which, in addition to provision of a dedicated pedal desk in individual worker's office space, participants are supported to increase daily walking by at least 3000 steps/day; and 2) a usual working condition group (CON, n=20). The primary outcome is change in abdominal obesity operationalized as MRI-determined visceral adipose tissue (VAT). Secondary outcomes include changes in body weight, total adipose tissue, subcutaneous adipose tissue, blood pressure, blood lipids, fasting glucose and insulin, [HbA1c], free-living accelerometer-determined walking (steps/day and cadence), time spent in sedentary behavior, exercise (time spent at moderate-to-vigorous physical activity), and dietary intake. We will electronically track daily steps data for WMPD participants and also duration of use and cadence (rpm) of pedal desks. Layering a step-counting intervention on top of a pedal desk intervention permits a clear evaluation of their separate and combined dose-response effects. Daily electronic tracking of pedal desk use and steps/day via automatic internet-based software enables continuous tracking of both behaviors for tailored feedback, behavioral shaping, and evaluation purposes. The expected outputs and outcomes of WorkACTIVE-P include providing clear feasibility and preliminary effectiveness evidence for a combination of practical technology-supported products and programs for Service Industry employers and workers interested in addressing health risk exposures (and related health care costs) associated with occupational sedentary behavior.

Project Summary / Abstract Accurately quantifying food intake is vital to promoting health and reducing chronic disease risk. Food intake encompasses energy intake, nutrient intake, and intake of various food groups (e.g., fruits, vegetables), and thus reflects the nutritional status of individuals. Nutrition affects disease risk, including risk of developing obesity, diabetes, and cancer, all of which negatively affect the United States (U.S). Despite its importance, accurately quantifying food intake has challenged researchers and clinicians for decades. Self-report methods (e.g., food records and diet recall) are a mainstay of nutritional epidemiology research, but their accuracy has been questioned, due, in part, to missing data and people inaccurately estimating portion size and recalling what they ate. Advances in assessing food intake over the past 15 years include technology-assisted approaches, including those that rely on food photography. Our group previously developed the Remote Food Photography Method (RFPM) and SmartIntake app, which quantifies food intake based on food images that users capture before and after they eat. Accurate estimates of food intake are obtained with this method in most study populations and settings, yet analysis of the images takes time and resources, requires a human rater, and users do not receive immediate feedback about their food intake. We developed the PortionSize smartphone app to overcome these limitations. The PortionSize app relies on users capturing images of their food selection and waste, but it immediately provides users with food intake data. The PortionSize app includes innovative technology to minimize missing data and to help users accurately estimate portion size. Preliminary data supports the validity of the PortionSize app, and during the proposed research the reliability and validity of PortionSize and MyFitnessPal, a commonly used smartphone-based food record, will be tested against `gold-standard' criterion measures. Specifically, the apps will be tested in healthy adults under the following three conditions: 1) laboratory-based test meals (Study 1), 2) free-living conditions, where participants will consume pre-weighed food from a cooler, which provides a test of energy and nutrient intake in free-living conditions (Study 2), and 3) free-living conditions, where energy intake is also assessed by doubly labeled water (Study 3). If found to be valid, the PortionSize app will move the field forward by providing a method that could widely and affordably be disseminated to assess food intake and foster/track adherence to personalized diets in real time.

PROJECT SUMMARY The world's population is aging in an obesogenic environment characterized by increased availability of high caloric, non-nutritious foods and reduced needs for physical activity. As a result, more people than ever are affected by chronic age-associated diseases, such as obesity, heart disease and diabetes. Thus, people are living longer but with shorter healthspans, or fewer years that are unaffected by disease. This imposes significant health and economic burdens on people, societies and nations. There is a critical need to develop and test sustainable lifestyle interventions to slow the rate of biological aging, extend healthspan and enhance quality of life as people age. One such intervention is calorie restriction (CR), which is defined as eating a nutritionally adequate diet that is below energy requirements. CR has been studied for almost 100 years and has been found to extend the lifespan and healthspan of numerous species. When tested in young and middle- aged humans, modest CR improves healthspan and slows biological aging. Nonetheless, adherence to CR has been found to decrease over time, calling into question the long-term viability of this approach, though earlier CR interventions did not benefit from a more advanced intervention approach, namely, a Just-in-Time Adaptive Intervention (JITAI). JITAIs strive to provide individuals with the right type and amount of personalized support when needed by adapting intervention delivery to the present needs and environment of the subject. A possible alternative to CR that may have better adherence and acceptability is time-restricted eating (TRE), which involves eating one's food in an 8 to 10-hour period of the day. TRE extends the lifespan of rodents, and, based on recent human trials, TRE improved disease risk factors and biomarkers of aging. Further, many benefits of TRE were achieved even when weight loss did not occur. In response to RFA-AG-21-016, we propose a novel planning project to determine the feasibility and preliminary efficacy of CR and TRE, which will be delivered in traditional intervention formats and as JITAIs. Data from the planning project will be used to select the CR intervention and identify if and what type of TRE intervention will be tested in a future 5-year trial. Further, evaluation of CR and TRE JITAIs, in comparison to more traditional approaches, is critical to allow us to weigh efficacy in relation to the burden of, and satisfaction with, these very different intervention approaches. Our project will also provide effect size estimates for a suite of primary and secondary aging outcomes to adequately power a 5-year trial, and it will provide important preliminary data on adherence and subject satisfaction and safety. Finally, the planning project will bring together a multidisciplinary team of scientists from across the US and allow the two study sites to establish a common protocol and standardize procedures necessary to execute a 5-year trial.

PROJECT SUMMARY/ABSTRACT (HUMAN PHENOTYPING CORE; HPC) The Human Phenotyping Core (HPC) and its two sub-cores (Energy Balance Sub-core and Behavioral Sub- core) directly support the research of NORC members by providing innovative clinical and intervention services to phenotype humans in mechanistic, clinical, and translational studies. The HPC supports research projects on ?nutrition, obesity, and metabolic health through the lifespan?, which is the overall theme of the Pennington/Louisiana NORC. The services of t h e Energy Balance Sub-core include methods to quantify body composition, energy expenditure, carbohydrate metabolism, and cardiorespiratory fitness. The services of the Behavioral Sub-core include behavioral, cognitive, and psychological assessments; measurement of food intake in laboratory and free-living conditions; design and delivery of behavioral change interventions; and assessment of activity and sedentary behavior in free-living conditions. The HPC has a 15-year history of: a) providing comprehensive services for phenotyping individuals throughout the lifespan, b) developing, validating, and establishing quality control procedures for innovative phenotyping methods and interventions, a n d c) establishing a large base of core users. Over the last cycle (years 11- 15), the HPC was rated very highly by NORC members and was exceptionally productive, having supported 94 projects and 194 publications. The HPC also expanded its imaging capabilities and established the Pennington/Louisiana NORC Biorepository over the last cycle. The Aims of the current renewal application to fund years 16-20 (2021-2025) are to: 1) provide members with consultation, specialist expertise and a comprehensive suite of innovative energy balance and behavioral services to characterize human subjects and continue to develop unique and cutting- edge phenotyping services, 2) promote translational research by supporting ?bench to bedside and back again? projects, as well as research to evaluate the translation and implementation of empirically supported treatments in clinics in the community, 3) provide training on nutrition and obesity research and human phenotyping via the planned Nutrition and Obesity Research Methods courses, and continue to facilitate pilot and feasibility studies that rely on the HPC, including use of, and contributions to, the Pennington/Louisiana NORC Biorepository, and 4) expand the data biorepository to include metabolic tissues (muscle, adipose) and biospecimens from special populations (pregnant and lactating women and bariatric surgery) that are needed for ongoing fundamental and translational studies of nutrition, obesity, and metabolic health throughout the lifespan.