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1.
J Nutr ; 154(7): 2133-2142, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38735574

RESUMEN

BACKGROUND: Current recommendation for lysine in older adults, 30 mg/kg/d, is based on young adult data. Evidence suggests that amino acid requirements may differ between young and old adults with both sex and age having an effect in the elderly. OBJECTIVES: This study aimed to define the lysine requirements in healthy older adults using the indicator amino acid oxidation (IAAO) method with L-[1-13C] phenylalanine as the indicator and to compare the derived estimates based on age: 60-69 y and >70 y. METHODS: Fourteen healthy males and 16 healthy females [>60 y, body mass index (BMI) = 26.3 kg/m2] were randomly assigned to receive 3-7 lysine intakes from 10 to 80 mg/kg/d. Subjects were adapted to a standard liquid diet providing 1.0 g/kg/d protein and adequate energy, for 2 d, with indicator oxidation measurements performed on day 3. The rate of release of 13CO2 from the oxidation of L-[1-13C] phenylalanine was measured in breath. A 2-phase linear mixed-effect model, and parametric bootstrap were used to determine mean lysine requirements and the 95% confidence intervals (CIs). The overlap of the 95% CI between the 2 age groups were used to compare the requirement estimates. The null hypothesis was accepted if the interval contained zero. RESULTS: The mean and upper 95% CI of the lysine requirement for females were 32.9 and 40.9 and 46.2 and 53.7 mg/kg/d for those aged 60-69 y and >70 y, respectively. The mean and upper 95% CI of the lysine requirement for the 2 groups of males were not different so was combined to yield a mean and 95% CI of 32.2 and 38.2 mg/kg/d. CONCLUSIONS: To our knowledge, this is the first study to report on the lysine requirement in adults aged >60 y. These results provide a basis from which the adequacy of diets to meet lysine needs of older adults can be assessed. The trial was registered at clinicaltrials.gov as NCT02008955 (https://clinicaltrials.gov/study/NCT02008955).


Asunto(s)
Lisina , Necesidades Nutricionales , Humanos , Lisina/administración & dosificación , Masculino , Femenino , Anciano , Persona de Mediana Edad , Factores de Edad , Dieta , Factores Sexuales , Anciano de 80 o más Años , Oxidación-Reducción
2.
PLoS Comput Biol ; 20(4): e1012015, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38620017

RESUMEN

Recent advances in single-cell sequencing technology have provided opportunities for mathematical modeling of dynamic developmental processes at the single-cell level, such as inferring developmental trajectories. Optimal transport has emerged as a promising theoretical framework for this task by computing pairings between cells from different time points. However, optimal transport methods have limitations in capturing nonlinear trajectories, as they are static and can only infer linear paths between endpoints. In contrast, stochastic differential equations (SDEs) offer a dynamic and flexible approach that can model non-linear trajectories, including the shape of the path. Nevertheless, existing SDE methods often rely on numerical approximations that can lead to inaccurate inferences, deviating from true trajectories. To address this challenge, we propose a novel approach combining forward-backward stochastic differential equations (FBSDE) with a refined approximation procedure. Our FBSDE model integrates the forward and backward movements of two SDEs in time, aiming to capture the underlying dynamics of single-cell developmental trajectories. Through comprehensive benchmarking on multiple scRNA-seq datasets, we demonstrate the superior performance of FBSDE compared to other methods, highlighting its efficacy in accurately inferring developmental trajectories.


Asunto(s)
Modelos Teóricos , Procesos Estocásticos
3.
Am J Clin Nutr ; 119(4): 917-926, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38325765

RESUMEN

BACKGROUND: Protein recommendations for older adults are based on nitrogen balance data from young adults. Physiological studies using the indicator amino acid oxidation method suggest they need 30% to 50% more protein than current recommendations. We herein present glutathione (GSH) as a physiological estimate of protein adequacy in older adults. OBJECTIVES: The objective was to measure GSH kinetics in response to varying protein intakes in a repeated-measures design in healthy adults aged ≥60 y using the precursor-product method. METHODS: Sixteen healthy older adults (n = 8 male and n = 8 female; body mass index ≤30 kg/m2) were studied. Each received 4 of 6 protein intakes in random order (0.66, 0.8, 0.9, 1.1, 1.3 and 1.5 g⋅kg-1⋅d-1). At each intake level, participants underwent isotope infusion studies of 7 h duration following a 3-d adaptation to the test level of protein. On the fourth day, GSH fractional (FSR) and absolute synthesis (ASR) rates were quantified by measuring the incorporation of U-[13C2-15N]glycine into GSH at isotopic steady state. A mixed-effect change-point regression model was used to determine a breakpoint in FSR and ASR. Secondary outcomes included plasma concentrations of oxidative stress markers, homocysteine, 5-L-oxoproline (5-OP), and urinary sulfate. The effect of secondary outcomes on GSH kinetics was analyzed using a joint linear mixed-effect model and Tukey's post hoc test. RESULTS: A protein intake of 1.08 g⋅kg-1⋅d-1 (95% confidence interval [CI]: 0.83, 1.32; Rm2 = 0.207; Rc2 = 0.671; P < 0.001) maximized GSH FSR. There was no effect of protein intake on concentrations of erythrocyte GSH, plasma homocysteine, oxidative stress markers, or 5-OP (P > 0.05). Protein intake had a positive effect on urinary sulfate excretion (P < 0.0001). CONCLUSION: A protein intake of 1.08 g⋅kg-1⋅d-1 from a high-quality protein maximized GSH synthesis in adults ≥60 y. This lends support to data suggesting a requirement higher than the current recommendation. This study was registered at clinicaltrials.gov as NCT02971046.


Asunto(s)
Eritrocitos , Glutatión , Adulto Joven , Humanos , Masculino , Femenino , Anciano , Glutatión/análisis , Glutatión/metabolismo , Eritrocitos/química , Glicina , Homocisteína/metabolismo , Sulfatos/análisis , Sulfatos/metabolismo
4.
Am J Clin Nutr ; 119(2): 371-383, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37992970

RESUMEN

BACKGROUND: In 2005, the Institute of Medicine advised using methods other than nitrogen balance (NB) for determining protein requirements. Since then, protein requirements using indicator amino acid oxidation (IAAO) have been published and are higher than NB. Glutathione (GSH), a tripeptide of cysteine, glutamate, and glycine, is a principal antioxidant that can be used as a functional indicator of protein adequacy. OBJECTIVES: The aim of this study was to measure changes in erythrocyte GSH kinetics [fractional synthesis rate (FSR) and absolute synthesis rate (ASR)] in healthy adults following a range of protein intakes at and above the current recommendations. METHODS: Sixteen healthy adults [8 males and 8 females, aged 25.6 ± 0.9 y (mean ± SEM)] were studied at 4 of 6 protein intakes ranging from 0.6 to 1.5 g⋅kg-1⋅d-1. Erythrocyte GSH kinetics were assessed during a 7-h infusion of [U-13C2-15N]glycine following 2 d of adaptation to each protein intake. Blood and urine tests were performed to measure oxidative stress markers, plasma homocysteine, triglycerides, plasma amino acid concentrations, 5-L-oxoproline (5-OP), and urinary sulfate. The protein intake that maximized GSH synthesis was determined using mixed-effect change-point regression in R. Primary and secondary outcomes were analyzed using linear mixed-effects and repeated-measures analysis of variance with Tukey's post hoc test. RESULTS: The protein intake that maximized GSH FSR at 78%⋅d-1 was 1.0 g⋅kg-1⋅d-1 (95% confidence interval: 0.63, 1.39). GSH ASR was significantly lower at 0.6 and 0.8 g⋅kg-1⋅d-1 than at 1.5 g⋅kg-1⋅d-1 (2.03 and 2.17, respectively, compared with 3.71 mmol⋅L-1⋅d-1). Increasing the protein intake led to increased urinary sulfate but did not affect erythrocyte GSH concentration, plasma oxidative stress markers, triglycerides, homocysteine, or 5-OP. CONCLUSIONS: A protein intake of 1.0 g⋅kg-1⋅d-1 maximized GSH synthesis, which is in agreement with earlier IAAO-derived protein requirements of 0.93 to 1.2 g⋅kg-1⋅d-1. These findings suggest that recommendations based on NB (0.66 g⋅kg-1⋅d-1) may underestimate protein needs for adequate health. This trial was registered at clinicaltrials.gov as NCT02971046.


Asunto(s)
Eritrocitos , Glutatión , Adulto , Femenino , Humanos , Masculino , Eritrocitos/metabolismo , Glutatión/metabolismo , Glicina , Homocisteína/metabolismo , Necesidades Nutricionales , Oxidación-Reducción , Sulfatos/metabolismo , Triglicéridos/metabolismo
5.
Nutrients ; 15(19)2023 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-37836396

RESUMEN

The minimum methionine requirement in the presence of excess dietary cysteine has not been determined in older adults. This study aimed to determine the minimum methionine requirement in healthy older adults using the indicator amino acid oxidation (IAAO) method. Fifteen healthy adults ≥ 60 years of age received seven methionine intakes (0 to 20 mg/kg/d) plus excess dietary cysteine (40 mg/kg/d). Oxidation of the indicator, L-[1-13C]phenylalanine (F13CO2), was used to estimate the mean minimum methionine requirement using a change-point mixed-effect model. There was no statistical difference between male and female requirement estimates, so the data were pooled to generate a mean of 5.1 mg/kg/d (Rm2 = 0.46, Rc2 = 0.77; p < 0.01; 95% CI: 3.67, 6.53 mg/kg/d). This is the first study to estimate the minimum methionine requirement in healthy older adults, which is the same between the sexes and as our lab's previous estimate in young adults. The findings are relevant considering current recommendations for increased consumption of plant foods, which will help to establish the appropriate balance of methionine and cysteine intake required to satisfy the sulphur amino acid requirements of older adults.


Asunto(s)
Cisteína , Metionina , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Metionina/metabolismo , Cisteína/metabolismo , Isótopos de Carbono , Necesidades Nutricionales , Relación Dosis-Respuesta a Droga , Racemetionina/metabolismo , Oxidación-Reducción
7.
J Pediatr Gastroenterol Nutr ; 77(4): 558-564, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37434279

RESUMEN

OBJECTIVES: Data on the relationship between body composition (BC) and physical activity (PA) in children with intestinal failure (IF) are lacking. The objectives were to collect data on PA and BC in children with IF, both parenterally and enterally fed, and to assess the relationship between PA and BC. METHODS: Cross-sectional study in children 5-18 years with IF including those receiving parenteral nutrition (PN) and those fully enterally fed. PA levels were measured using accelerometry. BC was measured by dual-energy X-ray absorptiometry. Data were compared to age- and sex-matched population norms using t tests. Regression analysis assessed the relationship between BC and PA. RESULTS: Fifty-eight children with IF (38 males), mean (SD) age of 10.0 (3.5) years, 20 dependent on PN were included. Patients with IF had significantly fewer steps per day ( P ≤ 0.001) compared with literature controls, with a mean (SD) of 7,972 (3,008) and 11,749 (1,106), respectively. There were no significant differences between patients receiving PN and those enterally fed, but both groups were significantly less active than literature controls ( P < 0.001). Patients with IF had higher fat mass and lower fat-free mass compared to literature controls ( P = 0.008). PA had a significant effect on BC ( r2 = 0.32, P < 0.001). CONCLUSIONS: Children with IF, those receiving PN and those fully enterally fed, are at risk of decreased PA and altered BC. PA should be part of ongoing rehabilitation and management to optimize outcomes.


Asunto(s)
Insuficiencia Intestinal , Masculino , Niño , Humanos , Estudios Transversales , Nutrición Parenteral , Composición Corporal , Ejercicio Físico
8.
Am J Clin Nutr ; 118(3): 538-548, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37356549

RESUMEN

BACKGROUND: The total sulfur amino acid (TSAA) recommendation in older adults is based on data from young adults. Physiological evidence suggests that older adults have a higher requirement than young adults. OBJECTIVES: The objective of this study was to determine the TSAA requirement in healthy men and women aged ≥60 y. METHODS: The TSAA requirement was determined using the indicator amino acid oxidation method with L-[1-13C]phenylalanine as the indicator. At recruitment, 15 older adults (n = 7 men and n = 8 women; BMI < 30 kg/m2) were assigned to receive 7 methionine intakes (5, 10, 15, 19, 25, 35, and 40 mg/kg/d) without dietary cysteine. Intake levels were randomly assigned to each subject. Following enrollment, 2 subjects completed 2 intakes and 3 completed 3, while the remainder completed all 7. Mean TSAA requirement was determined from oxidation of L-[1-13C]phenylalanine using a mixed-effect change-point model. The 95% CI was calculated using parametric bootstrap. To test whether breakpoints were different between men and women, the overlap in the 95% CI was calculated. RESULTS: The mean TSAA requirement was 26.2 (Rm2 = 0.39, Rc2 = 0.89; P < 0.001) and 17.1 mg/kg/d (Rm2 = 0.22, Rc2 = 0.79; P < 0.001) for men and women, respectively. The requirement was significantly higher in men than in women (difference in CI: 9.1 ± 8.85). CONCLUSIONS: To our knowledge, this is the first study to determine the TSAA requirement in older adults. The requirement in older women is similar to current recommendations but is 75% higher in older men. These findings are important given recommendations for increased plant protein consumption. They will help in the assessment of diet quality and provide the basis of dietary guidelines for older adults consuming a plant-based diet. This trial was registered at clinicaltrials.gov as NCT04595188.


Asunto(s)
Aminoácidos Sulfúricos , Necesidades Nutricionales , Anciano , Femenino , Humanos , Masculino , Aminoácidos/metabolismo , Isótopos de Carbono , Oxidación-Reducción , Fenilalanina/metabolismo
9.
JPEN J Parenter Enteral Nutr ; 47(7): 920-929, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37355855

RESUMEN

BACKGROUND: The objective of the study was to compare bioelectrical impedance analysis (BIA) and skinfolds with dual energy x-ray absorptiometry (DXA) in the assessment of body composition of children with intestinal failure. DXA is the reference method for body composition assessment in clinical settings. METHODS: Children aged 1-18 years with intestinal failure whohave DXA as part of routine clinical monitoring were eligible. BIA measured total body water on the same day as DXA. Skinfold measurements were taken at four sites: triceps, biceps, subscapular, and suprailiac. Percentage of fat mass (%FM) and fat-free mass (%FFM) were derived from resistance and reactance measured by BIA by using age-specific equations. Percentage of FM was calculated from skinfold measures by using age-specific equations. Data on patient characteristics, intestinal failure-related factors, and feeding method were collected. Paired t test examined differences in %FM and %FFM and Bland-Altman analysis determined the agreement between BIA, skinfolds, and DXA. Marginal linear model assessed the effect of age, sex, and feeding method on the difference in body composition obtained between DXA and BIA and between DXA and skinfolds. RESULTS: Sixty-eight children with intestinal failure, mean age 8.9 ± 4.2 years, were studied. There was no difference between %FFM and %FM obtained by DXA and BIA (P = 0.26), with a mean bias (95% CI) of -0.69 (-1.9 to 0.5) for %FFM. Sex and age were individually and jointly associated with the bias observed between DXA and BIA (P < 0.05). Skinfold and DXA measurements were significantly different (P < 0.05). CONCLUSIONS: BIA is an acceptable clinical tool for assessing body composition in pediatric intestinal failure.


Asunto(s)
Insuficiencia Intestinal , Humanos , Niño , Preescolar , Adolescente , Impedancia Eléctrica , Composición Corporal , Absorciometría de Fotón/métodos , Sesgo , Índice de Masa Corporal , Reproducibilidad de los Resultados
10.
J Nutr ; 153(7): 2016-2026, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37004875

RESUMEN

BACKGROUND: The indicator amino acid oxidation (IAAO) method is minimally invasive; therefore, it is applicable to study the amino acid (AA) requirements of individuals in various age groups. However, the accuracy of this method has been criticized because of the 8 h (1 d) protocol, which has been suggested to be too short an adaptation time for estimating AA requirements. OBJECTIVES: The IAAO method was used to determine whether 3 or 7 d of adaptation to each threonine intake alters the threonine requirement in adult men compared to 1 d of adaptation. METHODS: Eleven healthy adult men (19-35 y, body mass index (BMI) 23.4 in kg⋅m-2) were studied at 6 threonine intakes; each intake was studied over a 9 d period. Following 2 d of pre-adaptation to adequate protein intake (1.0 g·kg-1⋅d-1), subjects received experimental diets containing the randomly assigned test threonine intake (5, 10, 15, 20, 25, or 35 mg·kg-1·d-1) for 7 d. IAAO studies were performed on days 1, 3, and 7 of adaptation to the experimental diet. The rate of release of 13CO2 from the oxidation of L-[1-13C]phenylalanine (F13CO2) was measured, and the threonine requirement was determined by applying mixed-effect change-point regression to the F13CO2 data in R version 4.0.5. The 95% confidence interval (CI) was calculated using parametric bootstrap, and the requirement estimates on days 1, 3, and 7 were compared using analysis of variance (ANOVA). RESULTS: The mean threonine requirements (upper, lower 95% CI) for days 1, 3, and 7 were 10.5 (5.7, 15.9), 10.6 (7.5, 13.7), and 12.1 (9.2, 15.0 mg·kg-1·d-1), respectively; and these requirements were not statistically different (P = 0.213). CONCLUSIONS: We demonstrated that the short, 8 h IAAO protocol results in a threonine requirement that is not statistically different from that obtained on days 3 or 7 of adaptation in healthy adult males. This trial was registered at www. CLINICALTRIALS: gov as NCT04585087.


Asunto(s)
Aminoácidos , Treonina , Humanos , Masculino , Adulto Joven , Aminoácidos/metabolismo , Dióxido de Carbono/metabolismo , Isótopos de Carbono , Necesidades Nutricionales , Oxidación-Reducción , Fenilalanina/metabolismo
11.
Rev Sci Instrum ; 94(2): 025006, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36859003

RESUMEN

To solve the problem of multiphase holdup measurement, a new dual-receiver fiber-optical probe array multiphase logging tool (NDRFOPA_MLT) is designed and developed. This paper first constructed the mechanism model of an NDRFOP for phase holdup measurement by using the ray tracing method and theoretically analyzed the feasibility of NDRFOP to measure phase holdup; considering the shortcomings of NDRFOP local measurement, a NDRFOPA sensor for oil production three-phase flow is designed and developed. At the same time, the volume of fluid model was used to simulate the distribution characteristics of the medium in the NDRFOPA_MLT measurement pipeline under the working conditions of oil-gas-water flow with a total flow rate range of 0.42-1.25 m3/h, water holdup range of 50%-80%, oil holdup range of 10%-30%, and gas holdup range of 10%-40%. In addition, the NDRFOPA_MLT measurement models for different multiphase flow conditions were established by the ZEMAX ray tracing method, and the sensitivity distribution, response characteristics, and phase holdup measurement methods were studied to obtain the phase holdup measurement results under multiphase flow conditions. Finally, a multiphase flow experimental platform with a measurement pipe diameter of 20 mm and a measurement pipe length of 300 mm was established, and experiments were conducted under multiphase flow conditions, such as a gas flow rate range of 0.04-0.16 m3/h, oil flow rate range of 0.64-1.70 m3/h, and water flow rate range of 0.53-2.58 m3/h. The experimental results showed that phase holdup measurement error was mainly kept within 10%.

12.
Biometrics ; 79(2): 903-914, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-35043393

RESUMEN

Causal inference has been increasingly reliant on observational studies with rich covariate information. To build tractable causal procedures, such as the doubly robust estimators, it is imperative to first extract important features from high or even ultra-high dimensional data. In this paper, we propose causal ball screening for confounder selection from modern ultra-high dimensional data sets. Unlike the familiar task of variable selection for prediction modeling, our confounder selection procedure aims to control for confounding while improving efficiency in the resulting causal effect estimate. Previous empirical and theoretical studies suggest excluding causes of the treatment that are not confounders. Motivated by these results, our goal is to keep all the predictors of the outcome in both the propensity score and outcome regression models. A distinctive feature of our proposal is that we use an outcome model-free procedure for propensity score model selection, thereby maintaining double robustness in the resulting causal effect estimator. Our theoretical analyses show that the proposed procedure enjoys a number of properties, including model selection consistency and pointwise normality. Synthetic and real data analysis show that our proposal performs favorably with existing methods in a range of realistic settings. Data used in preparation of this paper were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.


Asunto(s)
Modelos Estadísticos , Modelos Teóricos , Simulación por Computador , Puntaje de Propensión , Causalidad
13.
Hippocampus ; 33(1): 37-46, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36519826

RESUMEN

Although recent studies support significant differences in intrinsic structure, function, and connectivity along the longitudinal axis of the hippocampus, few studies have investigated the normative development of this dimension. In addition, factors known to influence hippocampal structure, such as sex or puberty, have yet to be characterized when assessing age-related effects on its subregions. This study addresses this gap by investigating the relationship of the anterior (antHC) and posterior (postHC) hippocampus volumes with age, and how these are moderated by sex or puberty, in structural magnetic resonance imaging scans from 183 typically developing participants aged 6-21 years. Based on previous literature, we first anticipated that non-linear models would best represent the relationship between age and the antHC and postHC volumes. We found that age-related effects are region-specific, such that the antHC volume remains stable with increasing age, while the postHC shows a cubic function characterized by overall volume increase with age but a slower rate during adolescence. Second, we hypothesized that models, which include biological sex or pubertal status would best describe these relationships. Contrary to expectation, models comprising either biological sex or pubertal status did not significantly improve model performance. Further longitudinal research is needed to evaluate their effects on the antHC and postHC development.


Asunto(s)
Hipocampo , Pubertad , Adolescente , Humanos , Hipocampo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos
14.
Biometrika ; 109(1): 265-272, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35264813

RESUMEN

Unobserved confounding presents a major threat to causal inference in observational studies. Recently, several authors have suggested that this problem could be overcome in a shared confounding setting where multiple treatments are independent given a common latent confounder. It has been shown that under a linear Gaussian model for the treatments,the causal effect is not identifiable without parametric assumptions on the outcome model. In this note, we show that the causal effect is indeed identifiable if we assume a general binary choice model for the outcome with a non-probit link. Our identification approach is based on the incongruence between Gaussianity of the treatments and latent confounder and non-Gaussianity of a latent outcome variable. We further develop a two-step likelihood-based estimation procedure.

15.
J Am Stat Assoc ; 117(540): 1656-1668, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-37009529

RESUMEN

Alzheimer's disease is a progressive form of dementia that results in problems with memory, thinking, and behavior. It often starts with abnormal aggregation and deposition of ß amyloid and tau, followed by neuronal damage such as atrophy of the hippocampi, leading to Alzheimers Disease (AD). The aim of this paper is to map the genetic-imaging-clinical pathway for AD in order to delineate the genetically-regulated brain changes that drive disease progression based on the Alzheimers Disease Neuroimaging Initiative (ADNI) dataset. We develop a novel two-step approach to delineate the association between high-dimensional 2D hippocampal surface exposures and the Alzheimers Disease Assessment Scale (ADAS) cognitive score, while taking into account the ultra-high dimensional clinical and genetic covariates at baseline. Analysis results suggest that the radial distance of each pixel of both hippocampi is negatively associated with the severity of behavioral deficits conditional on observed clinical and genetic covariates. These associations are stronger in Cornu Ammonis region 1 (CA1) and subiculum subregions compared to Cornu Ammonis region 2 (CA2) and Cornu Ammonis region 3 (CA3) subregions. Supplementary materials for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement.

16.
Med Image Anal ; 76: 102298, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34911013

RESUMEN

Deep Learning-based computational pathology algorithms have demonstrated profound ability to excel in a wide array of tasks that range from characterization of well known morphological phenotypes to predicting non human-identifiable features from histology such as molecular alterations. However, the development of robust, adaptable and accurate deep learning-based models often rely on the collection and time-costly curation large high-quality annotated training data that should ideally come from diverse sources and patient populations to cater for the heterogeneity that exists in such datasets. Multi-centric and collaborative integration of medical data across multiple institutions can naturally help overcome this challenge and boost the model performance but is limited by privacy concerns among other difficulties that may arise in the complex data sharing process as models scale towards using hundreds of thousands of gigapixel whole slide images. In this paper, we introduce privacy-preserving federated learning for gigapixel whole slide images in computational pathology using weakly-supervised attention multiple instance learning and differential privacy. We evaluated our approach on two different diagnostic problems using thousands of histology whole slide images with only slide-level labels. Additionally, we present a weakly-supervised learning framework for survival prediction and patient stratification from whole slide images and demonstrate its effectiveness in a federated setting. Our results show that using federated learning, we can effectively develop accurate weakly-supervised deep learning models from distributed data silos without direct data sharing and its associated complexities, while also preserving differential privacy using randomized noise generation. We also make available an easy-to-use federated learning for computational pathology software package: http://github.com/mahmoodlab/HistoFL.


Asunto(s)
Algoritmos , Privacidad , Técnicas Histológicas , Humanos
17.
J Nutr ; 152(3): 770-778, 2022 03 03.
Artículo en Inglés | MEDLINE | ID: mdl-34871427

RESUMEN

BACKGROUND: Sorghum is the fifth most consumed cereal grain but limiting in the indispensable amino acid lysine. Complementing sorghum with lentils can improve the quality of sorghum-based diets. However, knowledge of lysine bioavailability in sorghum is lacking. OBJECTIVES: The study objectives were to determine the bioavailability of lysine in sorghum and to assess the effect of complementation of sorghum and lentils in a mixed-meal format. METHODS: We studied 5 healthy young men (≤30 years; BMI <25 kg/m2) in a repeated-measure design using the indicator amino acid oxidation (IAAO) method, with L-[1-13C] phenylalanine as the indicator. Each subject participated in 8 determinations in random order. On the reference diet, subjects received 4 amounts of L-lysine (5, 8, 12, and 15 mg. kg-1 . d-1) from a crystalline amino acid mixture patterned after egg protein. On the test diet, they received 3 levels of lysine (8.2, 12.5, and 15.7 mg. kg-1 . d-1) from sorghum, and on the complementation diet they received 1 level of lysine from a mixed meal of sorghum and lentils. The bioavailability of lysine in sorghum was estimated by comparing the IAAO response to the test diet with the IAAO response to the reference diet using the slope-ratio method. Effectiveness of complementation was assessed by comparing the IAAO response to the mixed meal to the IAAO response to the test protein. RESULTS: The bioavailability of lysine from sorghum was 94%. Upon complementation with lentils, there was a decline in the oxidation of L-[1-13C] phenylalanine by 19% (P < 0.0495), reflecting an improvement in available lysine in the mixed meal due to increased lysine intake. CONCLUSIONS: Although the bioavailability of lysine in sorghum is high, its lysine content is limiting. Complementation with lentils in a 1:1 ratio is recommended to achieve the lysine requirement for adult men consuming a sorghum-based diet. This trial was registered at clinicaltrials.gov as NCT03411005.


Asunto(s)
Lens (Planta) , Sorghum , Adulto , Aminoácidos/metabolismo , Culinaria , Proteínas en la Dieta/metabolismo , Grano Comestible , Humanos , Lens (Planta)/metabolismo , Lisina/metabolismo , Masculino , Necesidades Nutricionales , Oxidación-Reducción , Fenilalanina/metabolismo , Sorghum/metabolismo
18.
Appl Opt ; 60(18): 5439-5450, 2021 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-34263784

RESUMEN

In order to effectively analyze the fluorescence distribution of sea surface oil film detected by laser-induced fluorescence (LIF), a novel, to the best of our knowledge, simulation model of the oil film fluorescence was established based on the Monte Carlo method. Using this simulation model, the fluorescence distribution of oil film with different thickness in emission direction and spatial distribution were analyzed. Based on the fluorescence mechanism model of oil film detected by LIF, a criterion for the LIF system calibration, i.e., the fluorescence intensity ratio between oil film and clean seawater (FIR) using the fluorescence collected from clean seawater as a reference was proposed. The validity of the fluorescence simulation model was verified by using the FIR results of theory and simulation. The fluorescence spectra of oil films with different thickness and FIR parameters of corresponding thickness were obtained by experiments. By analyzing the fluorescence spectra of different oil products and oil film thickness, the fluorescence influencing factors of oil film detected by LIF were obtained. The results show that the fluorescence coverage area increases gradually with the increase of oil film thickness. When the incident light is in the same direction as the fluorescence receiving direction, the obtained fluorescence intensity is larger. Moreover, the FIR used as the calibration criterion of the LIF monitoring system can effectively characterize the thickness of oil film on the sea surface for LIF to detect sea surface oil film in real applications.

19.
Neuropsychopharmacology ; 46(7): 1293-1299, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33479508

RESUMEN

The effects of common antidepressants on suicidal ideation (SI) is unclear. In the landmark STAR*D trial antidepressants were effective for Major Depressive Disorder (MDD) in early treatment phases, but less effective in later phases. The effects of antidepressants on SI across the entire sample of the STAR*D trial has never been investigated. We performed a secondary analysis of the STAR*D data with the primary outcome of change in score on the suicide item (item three) of the Hamilton Rating Scale for Depression (HRSD17) across all four study levels. We used descriptive statistics and logistic regression analyses. Pearson correlation was used for change in SI versus change in depression (HRSD16). Reduction in mean (SD) SI was greater in levels one: 0.29 (±0.78) (p < 0.001) and two: 0.26 (±0.88) (p < 0.001) than in levels three: 0.16 (±0.92) (p = 0.005) and four: 0.18 (±0.93) (p = 0.094). A history of past suicide attempts (OR 1.72, p = 0.007), comorbid medical illness (OR 2.23, p = 0.005), and a family history of drug abuse (OR 1.69, p = 0.008) were correlated with worsening of SI across level one. Treatment with bupropion (OR 0.24, p < 0.001) or buspirone (OR 0.24, p = 0.001) were correlated with lowering of SI across level two. Improvement in SI was correlated with improvement in overall depression (HRSD16) at level one: r(3756) = 0.48; level two: r(1027) = 0.38; level three: r(249) = 0.31; and level four: r(75) = 0.42 (p < 0.001 for all levels). Improvement in SI is limited with pharmacotherapy in patients with treatment-resistant depression. Treatments with known anti-suicidal effects in MDD, such as ECT, should be considered in these patients.


Asunto(s)
Trastorno Depresivo Mayor , Trastorno Depresivo Resistente al Tratamiento , Antidepresivos/uso terapéutico , Bupropión/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Resistente al Tratamiento/tratamiento farmacológico , Humanos , Ideación Suicida
20.
Am J Clin Nutr ; 113(2): 410-419, 2021 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-33330915

RESUMEN

BACKGROUND: Current national (34 mg . kg-1 . d-1) and international (39 mg kg-1 . d-1) recommendations for leucine in older adults are based on data from young adults. Evidence suggests that the leucine requirements of older adults are higher than those of young adults. OBJECTIVE: The objective of the current study was to directly determine the leucine requirements in healthy older adult male and female study participants aged >60 y. METHODS: Leucine requirement was determined using the indicator amino acid oxidation method (IAAO) with l-[1-13C]phenylalanine as the indicator. Sixteen older adults (n = 7 male and n = 9 female participants) were randomly assigned to receive 3 to 7 leucine intakes from 20 to 120 mg . kg-1 . d-1. The rate of release of 13CO2 from l-[1-13C]phenylalanine oxidation was measured, and breakpoint analysis was used to estimate the leucine requirement. The 95% CI was calculated using the parametric bootstrap method. RESULTS: The mean leucine requirement for male participants was 77.8 mg . kg-1 . d-1 (upper 95% CI: 81.0) and for female participants, it was 78.2 mg . kg-1 . d-1 (upper 95% CI: 82.0) with no sex effect based on body weight. The data were therefore combined to yield a mean of 78.5 mg . kg-1 d-1 (upper 95% CI: 81.0 mg . kg-1 . d-1 ) for both sexes. On the basis of fat-free mass, the mean ± SEM leucine requirements were 115 ± 3.2 and 127 ± 2.4 mg . kg-1 . d-1 for male and female participants, respectively (P < 0.005). CONCLUSIONS: The estimated leucine requirement of older adults is more than double the amount in current recommendations. These data suggest that leucine could be a limiting amino acid in the diet of older adults consuming the current RDA for protein and those consuming a plant-based diet. In view of the functional and structural role of leucine, especially its importance in muscle protein synthesis, current leucine recommendations of older adults should be revised. This trial was registered at clinicaltrials.gov as NCT03506126.


Asunto(s)
Envejecimiento , Leucina/administración & dosificación , Anciano , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Necesidades Nutricionales , Oxidación-Reducción , Fenilalanina/metabolismo
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