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Background: There is emerging evidence that cancer and its treatments may accelerate the normal aging process, increasing the magnitude and rate of decline in functional capacity. This accelerated aging process is hypothesized to hasten the occurrence of common adverse age-related outcomes in cancer survivors, including loss of muscle mass and decrease in physical function. However, there is no data describing age-related loss of muscle mass and its relation to physical function in the long-term in cancer survivors., Methods: This study protocol describes the use of a novel method of muscle mass measurement, D3-creatine dilution method (D3Cr), in a large sample (n~6000) of community dwelling postmenopausal women from the Women's Health Initiative (WHI). D3Cr will be used to obtain a direct measure of muscle mass remotely. Participants will be drawn from two sub-cohorts embedded within the WHI that have recently completed an in-home visit. Cancer survivors will be drawn from the Life and Longevity After Cancer (LILAC) cohort, and cancer-free controls will be drawn from the WHI Long Life Study 2. The overall objective of this study is to examine the antecedents and consequences of low muscle mass in cancer survivors. The study aims are to: 1) create age-standardized muscle mass percentile curves and z-scores to characterize the distribution of D3- muscle mass in cancer survivors and non-cancer controls, 2) compare muscle mass, physical function, and functional decline in cancer survivors and non- cancer controls, and 3) use machine learning approaches to generate multivariate risk-prediction algorithms to detect low muscle mass., Discussion: The D3Cr method will transform our ability to measure muscle mass in large-scale epidemiologic research. This study is an opportunity to advance our understanding of a key source of morbidity among older and long-term female cancer survivors. This project will fill knowledge gaps, including the antecedents and consequences of low muscle mass, and use innovative methods to overcome common sources of bias in cancer research. The results of this study will be used to develop interventions to mitigate the harmful effects of low muscle mass in older adults and promote healthy survivorship in cancer survivors in the old (>65) and oldest-old (>85) age groups., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Banack et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Low skeletal muscle mass (myopenia) is common in cancer populations and is associated with functional decline and mortality, but prior oncology studies did not assess total body skeletal muscle mass. Instead, they measured surrogates such as cross-sectional area (CSA) of skeletal muscle at L3 from computed tomography (CT) or appendicular lean mass (ALM) from dual-energy X-ray absorptiometry (DXA). D3-creatine (D3Cr) dilution is a non-invasive method to assess total body skeletal muscle mass, which has been examined in a variety of populations but not in cancer. To compare the associations of D3Cr muscle mass, CT CSA, and DXA ALM with myopenia and physical function, we conducted a cross-sectional study among 119 patients with colon cancer (2018-2022)., Methods: For each technique (D3Cr, CT and DXA), myopenia was defined as the lowest sex-specific quartile of its measurement. Physical function was measured by the short physical performance battery and grip strength. We calculated Pearson correlations (r) among three techniques, computed Cohen's kappa coefficients (κ) to assess the agreement of myopenia, and estimated Pearson correlations (r) of three techniques with physical function. All analyses were sex-specific., Results: Sixty-one (51.3%) participants were male, the mean (standard deviation) age was 56.6 (12.9) years, and most (68.9%) had high physical function (short physical performance battery: ≥11 points). Correlations and myopenia agreement among three techniques were greater in men than women; for example, regarding D3Cr muscle mass versus CT CSA, r was 0.73 (P < 0.001) for men versus 0.45 (P < 0.001) for women, and κ was 0.82 (95% CI: 0.65, 0.99) for men versus 0.24 (95% CI: -0.08, 0.52) for women. Among men, higher D3Cr muscle mass was significantly correlated with faster gait speed (r = 0.43, P < 0.01) and stronger grip strength (r = 0.32, P < 0.05); similar correlations were observed for CT CSA and DXA ALM. However, among women, no measure of muscle or lean mass was significantly associated with physical function., Conclusions: This is the first study using D3-creatine dilution method to assess muscle mass in a cancer population. Regardless of the techniques used for muscle or lean mass assessment, we observed stronger correlations, greater myopenia agreement, and more significant associations with physical function in men with colon cancer than women. D3Cr, CT and DXA are not interchangeable methods for assessing myopenia and physical function, especially in women with colon cancer. Future studies should consider relative advantages of these techniques and examine the D3-creatine dilution method in other cancer types., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background: Traditionally, weight loss (WL) trials utilize dual energy X-ray absorptiometry (DXA) to measure lean mass. This method assumes lean mass, as the sum of all non-bone and non-fat tissue, is a reasonable proxy for muscle mass. In contrast, the D 3 -creatine (D 3 Cr) dilution method directly measures whole body skeletal muscle mass, although this method has yet to be applied in the context of a geriatric WL trial. The purpose of this project was to (1) describe estimates of change and variability in D 3 Cr muscle mass in older adults participating in an intentional WL intervention and (2) relate its change to other measures of body composition as well as muscle function and strength., Methods: The INVEST in Bone Health trial (NCT04076618), used as a scaffold for this ancillary pilot project, is a three-armed, 12-month randomized, controlled trial designed to determine the effects of resistance training or weighted vest use during intentional WL on a battery of musculoskeletal health outcomes among 150 older adults living with obesity. A convenience sample of 24 participants (n = 8/arm) are included in this analysis. At baseline and 6 months, participants were weighed, ingested a 30 mg D 3 Cr tracer dose, provided a fasted urine sample 3-6 days post-dosage, underwent DXA (total body fat and lean masses, appendicular lean mass) and computed tomography (mid-thigh and trunk muscle/intermuscular fat areas) scans, and performed 400-m walk, stair climb, knee extensor strength, and grip strength tests., Results: Participants were older (68.0 ± 4.4 years), mostly White (75.0%), predominantly female (66.7%), and living with obesity (body mass index: 33.8 ± 2.7 kg/m 2 ). Six month total body WL was -10.3 (95% confidence interval, CI: -12.7, -7.9) kg. All DXA and computed tomography-derived body composition measures were significantly decreased from baseline, yet D 3 Cr muscle mass did not change [+0.5 (95% CI: -2.0, 3.0) kg]. Of muscle function and strength measures, only grip strength significantly changed [+2.5 (95% CI: 1.0, 4.0) kg] from baseline., Conclusions: Among 24 older adults, significant WL with or without weighted vest use or resistance training over a 6-month period was associated with significant declines in all bioimaging metrics, while D 3 Cr muscle mass and muscle function and strength were preserved. Treatment assignment for the trial remains blinded; therefore, full interpretation of these findings is limited. Future work in this area will assess change in D 3 Cr muscle mass by parent trial treatment group assignment in all study participants., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background: Given limited experience in applying the creatine-(methyl-D 3 ) (D 3 Cr) dilution method to measure skeletal muscle mass (SMM) in young children, the feasibility of deployment in a fielding setting and performance of the method was assessed in a cohort of 4-year-old children in Dhaka, Bangladesh., Methods: Following D 3 Cr oral dose (10 mg) administration, single fasting urine samples were collected at 2-4 days (n = 100). Twenty-four-hour post-dose collections and serial spot urine samples on days 2, 3 and 4 were obtained in a subset of participants (n = 10). Urinary creatine, creatinine, D 3 Cr and D 3 -creatinine enrichment were analyzed by liquid chromatography-tandem mass spectrometry. Appendicular lean mass (ALM) was measured by dual-energy x-ray absorptiometry and grip strength was measured by a hand-held dynamometer., Results: SMM was measured successfully in 91% of participants, and there were no adverse events. Mean ± SD SMM was greater than ALM (4.5 ± 0.4 and 3.2 ± 0.6 kg, respectively). Precision of SMM was low (intraclass correlation = 0.20; 95% CI: 0.02, 0.75; n = 10). Grip strength was not associated with SMM in multivariable analysis (0.004 kg per 100 g of SMM; 95% CI: -0.031, 0.038; n = 91)., Conclusions: The D 3 Cr dilution method was feasible in a community setting. However, high within-child variability in SMM estimates suggests the need for further optimization of this approach., Impact: The D3-creatine (D3Cr) stable isotope dilution method was considered a feasible method for the estimation of skeletal muscle mass (SMM) in young children in a community setting and was well accepted among participants. SMM was weakly associated with both dual-energy x-ray absorptiometry-derived values of appendicular lean mass and grip strength. High within-child variability in estimated values of SMM suggests that further optimization of the D3Cr stable isotope dilution method is required prior to implementation in community research settings., (© 2023. The Author(s).)

Background: Assessing whole-body skeletal muscle mass (SMM) and fat-free mass (FFM) is essential for the adequate nutritional management and training evaluation of athletes and trained individuals. This study aimed to determine the relationship between SMM assessed using the creatine (methyl-d 3 ) dilution (D 3 -creatine) method and SMM estimated by whole-body magnetic resonance imaging (MRI) in healthy young men undergoing exercise training. Additionally, we examined the association between FFM measured using the four-component (4C) method (FFM 4C ) and the total body protein value estimated using 4C (TBpro 4C )., Methods and Results: We analyzed the data of 29 males (mean age, 19.9 ± 1.8 years) who exercised regularly. SMM measurements were obtained using the D 3 -creatine method (SMM D3-creatine ) and MRI (SMM MRI ). The SMM D3-creatine adjusted to 4.3 g/SMM kg was significantly higher than SMM MRI (p < 0.01). The fit of the creatine pool size compared with SMM MRI was 5.0 g/SMM MRI kg. SMM MRI was significantly correlated with both SMM D3-creatine adjusted to 4.3 g/kg and 5.1 g/kg. TBpro 4C was significantly lower than SMM MRI (p < 0.01). Contrastingly, FFM 4C was significantly higher than SMM MRI (p < 0.01)., Conclusions: SMM D3-creatine adjusted to 4.3 g/SMM kg-a previously reported value-may differ for athletes and active young males. We believe that a value of 5.0-5.1 g/SMM kg better estimates the total muscle mass in this population. Traditional FFM estimation highly correlates with SMM MRI in well-trained young males, and the relationships appear strong enough for total body protein or SMM to be estimated through the FFM value., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The D3-creatine (D3Cr) dilution method provides a direct measure of skeletal muscle. The aim of this study was to compare the association of D3Cr muscle mass with lean body mass (LBM) measured by dual-energy x-ray absorptiometry (DXA) and examine its relation with physical function in postmenopausal women., Methods: Seventy-four community-dwelling women (mean age 82.3 ± 5.4) participated in this pilot study from the Buffalo, New York clinical site of the Women's Health Initiative (WHI). Participants attended a clinic visit which included anthropometric measures, blood draw, DXA scan, measures of physical function, and initiated the D3Cr protocol. Physical function was evaluated using hand grip strength, short physical performance battery (SPPB), and RAND-36 physical function scale. Descriptive statistics and logistic regression models were used to examine the associations of D3Cr muscle mass with functional outcomes., Results: D3-creatine muscle mass was moderately correlated with DXA LBM (r = 0.50) and DXA appendicular lean mass (ALM) (r = 0.50). Individuals with high D3Cr muscle mass (%) had higher physical function compared to individuals with low muscle mass (%), indicated by high scores on SPPB (odds ratio [OR] = 5.24; 95% confidence interval [CI]: 1.40, 19.58). We observed stronger relationships between high D3Cr and physical function than either DXA LBM (OR = 3.40; 95% CI: 0.88, 13.11) or DXA ALM (OR = 4.15; 95% CI: 1.10, 15.68) and physical function., Conclusions: Our findings provide strong preliminary data for the associations of D3Cr muscle mass with measures of physical function in older women. These findings support and extend prior work on D3Cr muscle mass in older men., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The rate of accrual of muscle mass in neonates has not been assessed. We describe the D 3 -creatine (D 3 Cr) dilution method, a noninvasive assessment of muscle mass in neonates., Methods: A total of 76 neonates >26-week-old corrected gestational age were enrolled and measured at 2-week intervals while admitted to a neonatal intensive care unit (NICU). Additional measures at 6 and 12-20 months after initial measurement were obtained if available. An enteral dose of 2 mg D 3 Cr in 0.5 mL 20% 2 H 2 O was used to determine muscle mass and total body water (TBW)., Results: Muscle mass by the D 3 Cr method was strongly associated with TBW and body weight (r = 0.9272, p < 0.0001 and r = 0.9435, p < 0.0001 for all time points and r = 0.6661, p < 0.0001 and r = 0.8634, p < 0.0001, respectively, while in the NICU). Change in muscle mass vs. change in body weight, TBW, and length were also strongly correlated., Conclusions: The D 3 Cr dilution method provides a noninvasive assessment of muscle mass accrual in neonates, which has not been previously possible and may be an important new tool for the evaluation of nutritional status and normal growth patterns., Impact: We describe a noninvasive method for the measurement of skeletal muscle mass neonates. At the present time, there is no direct measurement of muscle mass in infants available. The D 3 Cr dilution method is a direct and noninvasive measurement of muscle mass. Using a single enteral dose of D 3 Cr in 2 H 2 O followed by urine and saliva samples, rapid and substantial accrual of muscle mass and TBW is assessed. Assessment of muscle mass accrual in premature infants may be a strong indicator of nutritional status. Change in muscle mass is strongly related to change in weight and TBW.

Background: Direct assessment of skeletal muscle mass in older adults is clinically challenging. Relationships between lean mass and late-life outcomes have been inconsistent. The D3-creatine dilution method provides a direct assessment of muscle mass., Methods: Muscle mass was assessed by D3-creatine (D3Cr) dilution in 1,382 men (mean age, 84.2 years). Participants completed the Short Physical Performance Battery (SPPB); usual walking speed (6 m); and dual x-ray absorptiometry (DXA) lean mass. Men self-reported mobility limitations (difficulty walking 2-3 blocks or climbing 10 steps); recurrent falls (2+); and serious injurious falls in the subsequent year. Across quartiles of D3Cr muscle mass/body mass, multivariate linear models calculated means for SPPB and gait speed; multivariate logistic models calculated odds ratios for incident mobility limitations or falls., Results: Compared to men in the highest quartile, those in the lowest quartile of D3Cr muscle mass/body mass had slower gait speed (Q1: 1.04 vs Q4: 1.17 m/s); lower SPPB (Q1: 8.4 vs Q4: 10.4 points); greater likelihood of incident serious injurious falls (odds ratio [OR] Q1 vs Q4: 2.49, 95% confidence interval [CI]: 1.37, 4.54); prevalent mobility limitation (OR Q1 vs Q4,: 6.1, 95% CI: 3.7, 10.3) and incident mobility limitation (OR Q1 vs Q4: 2.15 95% CI: 1.42, 3.26); p for trend < .001 for all. Results for incident recurrent falls were in the similar direction (p = .156). DXA lean mass had weaker associations with the outcomes., Conclusions: Unlike DXA lean mass, low D3Cr muscle mass/body mass is strongly related to physical performance, mobility, and incident injurious falls in older men., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Muscle mass can be measured directly in vivo by isotope dilution, using Creatine-(methyl-d 3 ) monohydrate (D 3 -Cr) by mouth followed by measurement of the steady-state enrichment of D 3 -creatinine (D 3 -Crn) in urine. Isotope dilution methods require knowledge of the amount of tracer delivered to the pool of interest. In a subset of human subjects, a small amount of orally administered D 3 -Cr 'spills' into urine after absorption and prior to transport into skeletal muscle cells. The objectives were to develop a method to correct for spillage to compare the estimate of muscle mass by D 3 -Cr dilution to other assessments of fat-free mass., Methods: Subjects (19 males, 23-81 years old; 20 females, 20-77 years old) ingested a single dose of 60 mg D 3 -Cr and urine was collected prior to and daily for 4 days following the dose. Fasting morning urine samples was assessed for D 3 -Cr, total Cr, D 3 -Crn, and total Crn concentrations, as well as isotopic enrichments of D 3 -Crn, by LC/MS. The 24-h urine collections over 3 days after the dose of D 3 -Cr were also performed to determine D 3 -Cr spillage. Total body water, fat mass, and fat-free mass were assessed by bioelectrical impedance spectroscopy (BIS)., Results: Spillage of D 3 -Cr in the urine was greater in women than men. D 3 -Crn enrichment and the ratio of Cr/Crn were used in an algorithm to calculate Cr pool size and muscle mass. Specifically, an algorithm was developed for the estimation of spillage based on the relationship between the fasting Cr/Crn ratio and the cumulative proportion of the D 3 -Cr dose excreted over 3 days based on 24-h urine collections. Muscle mass corrected using the algorithm based on fasting urine levels correlated (r = 0.9967, P < 0.0001) with that corrected by measuring D 3 -Cr dose excreted. Muscle mass measured by D 3 -Crn enrichment also correlated (r = 0.8579, P < 0.0001, algorithm corrected) with that measured by 24-h Crn excretion. Muscle mass measured by D 3 -Cr dilution method correlated with intracellular water by BIS, whether using spillage corrected by the algorithm (r = 0.9041, P < 0.0001) or measured by 3 day D 3 -Cr losses (r = 0.91, P < 0.0001) and similarly correlated with fat-free mass by BIA (r = 0.8857 and 0.8929, P < 0.0001, respectively)., Conclusions: The D 3 -Cr dilution method is further validated here as a non-invasive, easy-to-use test for measuring muscle mass. The technical issue of D 3 -Cr spillage can be corrected for with a simple algorithm based on fasting spot urine samples. Muscle mass by Cr dilution potentially has broad applications in clinical and research settings., (© 2018 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

BackgroundGiven limited experience in applying the creatine-(methyl-D3) (D3Cr) dilution method to measure skeletal muscle mass (SMM) in young children, the feasibility of deployment in a fielding setting and performance of the method was assessed in a cohort of 4-year-old children in Dhaka, Bangladesh.MethodsFollowing D3Cr oral dose (10 mg) administration, single fasting urine samples were collected at 2-4 days (n = 100). Twenty-four-hour post-dose collections and serial spot urine samples on days 2, 3 and 4 were obtained in a subset of participants (n = 10). Urinary creatine, creatinine, D3Cr and D3-creatinine enrichment were analyzed by liquid chromatography-tandem mass spectrometry. Appendicular lean mass (ALM) was measured by dual-energy x-ray absorptiometry and grip strength was measured by a hand-held dynamometer.ResultsSMM was measured successfully in 91% of participants, and there were no adverse events. Mean ± SD SMM was greater than ALM (4.5 ± 0.4 and 3.2 ± 0.6 kg, respectively). Precision of SMM was low (intraclass correlation = 0.20; 95% CI: 0.02, 0.75; n = 10). Grip strength was not associated with SMM in multivariable analysis (0.004 kg per 100 g of SMM; 95% CI: -0.031, 0.038; n = 91).ConclusionsThe D3Cr dilution method was feasible in a community setting. However, high within-child variability in SMM estimates suggests the need for further optimization of this approach.ImpactThe D3-creatine (D3Cr) stable isotope dilution method was considered a feasible method for the estimation of skeletal muscle mass (SMM) in young children in a community setting and was well accepted among participants. SMM was weakly associated with both dual-energy x-ray absorptiometry-derived values of appendicular lean mass and grip strength. High within-child variability in estimated values of SMM suggests that further optimization of the D3Cr stable isotope dilution method is required prior to implementation in community research settings.

Boys with Duchenne muscular dystrophy (DMD) experience a progressive loss of functional muscle mass, with fibrosis and lipid accumulation. Accurate evaluation of whole‐body functional muscle mass (MM) in DMD patients has not previously been possible and the rate of synthesis of muscle proteins remains unexplored. We used non‐invasive, stable isotope‐based methods from plasma and urine to measure the fractional rate of muscle protein synthesis (FSR) functional muscle mass (MM), and fat free mass (FFM) in 10 DMD (6–17 years) and 9 age‐matched healthy subjects. An oral dose of D3creatine in 70% 2H2O was administered to determine MM and FFM followed by daily 70% 2H2O to measure protein FSR. Functional MM was profoundly reduced in DMD subjects compared to controls (17% vs. 41% of body weight, P < 0.0001), particularly in older, non‐ambulant patients in whom functional MM was extraordinarily low (<13% body weight). We explored the urine proteome to measure FSR of skeletal muscle‐derived proteins. Titin, myosin light chain and gelsolin FSRs were substantially lower in DMD subjects compared to controls (27%, 11% and 40% of control, respectively, P < 0.0001) and were strongly correlated. There were no differences in muscle‐derived sarcoplasmic proteins FSRs (creatine kinase M‐type and carbonic anhydrase‐3) measured in plasma. These data demonstrate that both functional MM, body composition and muscle protein synthesis rates can be quantified non‐invasively and are markedly different between DMD and control subjects and suggest that the rate of contractile but not sarcoplasmic protein synthesis is affected by a lack of dystrophin. Key points: Duchenne muscular dystrophy (DMD) results in a progressive loss of functional skeletal muscle but total body functional muscle mass or rates of muscle protein synthesis have not previously been assessed in these patients.D3‐creatine dilution was used to measure total functional muscle mass and oral 2H2O was used to examine the rates of muscle protein synthesis non‐invasively in boys with DMD and healthy controls using urine samples.Muscle mass was profoundly lower in DMD compared to control subjects, particularly in older, non‐ambulant patients.The rates of contractile protein synthesis but not sarcoplasmic proteins were substantially lower in DMD.These results may provide non‐invasive biomarkers for disease progression and therapeutic efficacy in DMD and other neuromuscular diseases. [ABSTRACT FROM AUTHOR]

Abstract: Background: Muscle mass can be measured directly in vivo by isotope dilution, using Creatine‐(methyl‐d3) monohydrate (D3‐Cr) by mouth followed by measurement of the steady‐state enrichment of D3‐creatinine (D3‐Crn) in urine. Isotope dilution methods require knowledge of the amount of tracer delivered to the pool of interest. In a subset of human subjects, a small amount of orally administered D3‐Cr ‘spills’ into urine after absorption and prior to transport into skeletal muscle cells. The objectives were to develop a method to correct for spillage to compare the estimate of muscle mass by D3‐Cr dilution to other assessments of fat‐free mass. Methods: Subjects (19 males, 23–81 years old; 20 females, 20–77 years old) ingested a single dose of 60 mg D3‐Cr and urine was collected prior to and daily for 4 days following the dose. Fasting morning urine samples was assessed for D3‐Cr, total Cr, D3‐Crn, and total Crn concentrations, as well as isotopic enrichments of D3‐Crn, by LC/MS. The 24‐h urine collections over 3 days after the dose of D3‐Cr were also performed to determine D3‐Cr spillage. Total body water, fat mass, and fat‐free mass were assessed by bioelectrical impedance spectroscopy (BIS). Results: Spillage of D3‐Cr in the urine was greater in women than men. D3‐Crn enrichment and the ratio of Cr/Crn were used in an algorithm to calculate Cr pool size and muscle mass. Specifically, an algorithm was developed for the estimation of spillage based on the relationship between the fasting Cr/Crn ratio and the cumulative proportion of the D3‐Cr dose excreted over 3 days based on 24‐h urine collections. Muscle mass corrected using the algorithm based on fasting urine levels correlated (r = 0.9967, P < 0.0001) with that corrected by measuring D3‐Cr dose excreted. Muscle mass measured by D3‐Crn enrichment also correlated (r = 0.8579, P < 0.0001, algorithm corrected) with that measured by 24‐h Crn excretion. Muscle mass measured by D3‐Cr dilution method correlated with intracellular water by BIS, whether using spillage corrected by the algorithm (r = 0.9041, P < 0.0001) or measured by 3 day D3‐Cr losses (r = 0.91, P < 0.0001) and similarly correlated with fat‐free mass by BIA (r = 0.8857 and 0.8929, P < 0.0001, respectively). Conclusions: The D3‐Cr dilution method is further validated here as a non‐invasive, easy‐to‐use test for measuring muscle mass. The technical issue of D3‐Cr spillage can be corrected for with a simple algorithm based on fasting spot urine samples. Muscle mass by Cr dilution potentially has broad applications in clinical and research settings. [ABSTRACT FROM AUTHOR]