Leveraging continuous glucose monitoring for personalized modeling of insulin-regulated glucose metabolism.

Continuous glucose monitoring (CGM) is a promising, minimally invasive alternative to plasma glucose measurements for calibrating physiology-based mathematical models of insulin-regulated glucose metabolism, reducing the reliance on in-clinic measurements. However, the use of CGM glucose, particularly in combination with insulin measurements, to develop personalized models of glucose regulation remains unexplored. Here, we simultaneously measured interstitial glucose concentrations using CGM as well as plasma glucose and insulin concentrations during an oral glucose tolerance test (OGTT) in individuals with overweight or obesity to calibrate personalized models of glucose-insulin dynamics. We compared the use of interstitial glucose with plasma glucose in model calibration, and evaluated the effects on model fit, identifiability, and model parameters' association with clinically relevant metabolic indicators. Models calibrated on both plasma and interstitial glucose resulted in good model fit, and the parameter estimates associated with metabolic indicators such as insulin sensitivity measures in both cases. Moreover, practical identifiability of model parameters was improved in models estimated on CGM glucose compared to plasma glucose. Together these results suggest that CGM glucose may be considered as a minimally invasive alternative to plasma glucose measurements in model calibration to quantify the dynamics of glucose regulation.

Quantifying the effect of nutritional interventions on metabolic resilience using personalized computational models.

The manifestation of metabolic deteriorations that accompany overweight and obesity can differ greatly between individuals, giving rise to a highly heterogeneous population. This inter-individual variation can impede both the provision and assessment of nutritional interventions as multiple aspects of metabolic health should be considered at once. Here, we apply the Mixed Meal Model, a physiology-based computational model, to characterize an individual's metabolic health in silico. A population of 342 personalized models were generated using data for individuals with overweight and obesity from three independent intervention studies, demonstrating a strong relationship between the model-derived metric of insulin resistance (ρ = 0.67, p < 0.05) and the gold-standard hyperinsulinemic-euglycemic clamp. The model is also shown to quantify liver fat accumulation and ß-cell functionality. Moreover, we show that personalized Mixed Meal Models can be used to evaluate the impact of a dietary intervention on multiple aspects of metabolic health at the individual level.

Postoperative circadian patterns in wearable sensor measured heart rate: a prospective observational study.

PURPOSE: This study aimed to describe the 24-hour cycle of wearable sensor-obtained heart rate in patients with deterioration-free recovery and to compare it with patients experiencing postoperative deterioration. METHODS: A prospective observational trial was performed in patients following bariatric or major abdominal cancer surgery. A wireless accelerometer patch (Healthdot) continuously measured postoperative heart rate, both in the hospital and after discharge, for a period of 14 days. The circadian pattern, or diurnal rhythm, in the wearable sensor-obtained heart rate was described using peak, nadir and peak-nadir excursions. RESULTS: The study population consisted of 137 bariatric and 100 major abdominal cancer surgery patients. In the latter group, 39 experienced postoperative deterioration. Both surgery types showed disrupted diurnal rhythm on the first postoperative days. Thereafter, the bariatric group had significantly lower peak heart rates (days 4, 7-12, 14), lower nadir heart rates (days 3-14) and larger peak-nadir excursions (days 2, 4-14). In cancer surgery patients, significantly higher nadir (days 2-5) and peak heart rates (days 2-3) were observed prior to deterioration. CONCLUSIONS: The postoperative diurnal rhythm of heart rate is disturbed by different types of surgery. Both groups showed recovery of diurnal rhythm but in patients following cancer surgery, both peak and nadir heart rates were higher than in the bariatric surgery group. Especially nadir heart rate was identified as a potential prognostic marker for deterioration after cancer surgery.

A data-driven computational model for obesity-driven diabetes onset and remission through weight loss.

Obesity is a major risk factor for the development of type 2 diabetes (T2D), where a sustained weight loss may result in T2D remission in individuals with obesity. To design effective and feasible intervention strategies to prevent or reverse T2D, it is imperative to study the progression of T2D and remission together. Unfortunately, this is not possible through experimental and observational studies. To address this issue, we introduce a data-driven computational model and use human data to investigate the progression of T2D with obesity and remission through weight loss on the same timeline. We identify thresholds for the emergence of T2D and necessary conditions for remission. We explain why remission is only possible within a window of opportunity and the way that window depends on the progression history of T2D, individual's metabolic state, and calorie restrictions. These findings can help to optimize therapeutic intervention strategies for T2D prevention or treatment.

Application of transfer learning to predict drug-induced human in vivo gene expression changes using rat in vitro and in vivo data.

The liver is the primary site for the metabolism and detoxification of many compounds, including pharmaceuticals. Consequently, it is also the primary location for many adverse reactions. As the liver is not readily accessible for sampling in humans; rodent or cell line models are often used to evaluate potential toxic effects of a novel compound or candidate drug. However, relating the results of animal and in vitro studies to relevant clinical outcomes for the human in vivo situation still proves challenging. In this study, we incorporate principles of transfer learning within a deep artificial neural network allowing us to leverage the relative abundance of rat in vitro and in vivo exposure data from the Open TG-GATEs data set to train a model to predict the expected pattern of human in vivo gene expression following an exposure given measured human in vitro gene expression. We show that domain adaptation has been successfully achieved, with the rat and human in vitro data no longer being separable in the common latent space generated by the network. The network produces physiologically plausible predictions of human in vivo gene expression pattern following an exposure to a previously unseen compound. Moreover, we show the integration of the human in vitro data in the training of the domain adaptation network significantly improves the temporal accuracy of the predicted rat in vivo gene expression pattern following an exposure to a previously unseen compound. In this way, we demonstrate the improvements in prediction accuracy that can be achieved by combining data from distinct domains.

Quantifying postprandial glucose responses using a hybrid modeling approach: Combining mechanistic and data-driven models in The Maastricht Study.

Computational models of human glucose homeostasis can provide insight into the physiological processes underlying the observed inter-individual variability in glucose regulation. Modelling approaches ranging from "bottom-up" mechanistic models to "top-down" data-driven techniques have been applied to untangle the complex interactions underlying progressive disturbances in glucose homeostasis. While both approaches offer distinct benefits, a combined approach taking the best of both worlds has yet to be explored. Here, we propose a sequential combination of a mechanistic and a data-driven modeling approach to quantify individuals' glucose and insulin responses to an oral glucose tolerance test, using cross sectional data from 2968 individuals from a large observational prospective population-based cohort, the Maastricht Study. The best predictive performance, measured by R2 and mean squared error of prediction, was achieved with personalized mechanistic models alone. The addition of a data-driven model did not improve predictive performance. The personalized mechanistic models consistently outperformed the data-driven and the combined model approaches, demonstrating the strength and suitability of bottom-up mechanistic models in describing the dynamic glucose and insulin response to oral glucose tolerance tests.

Machine Learning for Postoperative Continuous Recovery Scores of Oncology Patients in Perioperative Care with Data from Wearables.

Assessing post-operative recovery is a significant component of perioperative care, since this assessment might facilitate detecting complications and determining an appropriate discharge date. However, recovery is difficult to assess and challenging to predict, as no universally accepted definition exists. Current solutions often contain a high level of subjectivity, measure recovery only at one moment in time, and only investigate recovery until the discharge moment. For these reasons, this research aims to create a model that predicts continuous recovery scores in perioperative care in the hospital and at home for objective decision making. This regression model utilized vital signs and activity metrics measured using wearable sensors and the XGBoost algorithm for training. The proposed model described continuous recovery profiles, obtained a high predictive performance, and provided outcomes that are interpretable due to the low number of features in the final model. Moreover, activity features, the circadian rhythm of the heart, and heart rate recovery showed the highest feature importance in the recovery model. Patients could be identified with fast and slow recovery trajectories by comparing patient-specific predicted profiles to the average fast- and slow-recovering populations. This identification may facilitate determining appropriate discharge dates, detecting complications, preventing readmission, and planning physical therapy. Hence, the model can provide an automatic and objective decision support tool.

E-DES-PROT: A novel computational model to describe the effects of amino acids and protein on postprandial glucose and insulin dynamics in humans.

Current computational models of whole-body glucose homeostasis describe physiological processes by which insulin regulates circulating glucose concentrations. While these models perform well in response to oral glucose challenges, interaction with other nutrients that impact postprandial glucose metabolism, such as amino acids (AAs), is not considered. Here, we developed a computational model of the human glucose-insulin system, which incorporates the effects of AAs on insulin secretion and hepatic glucose production. This model was applied to postprandial glucose and insulin time-series data following different AA challenges (with and without co-ingestion of glucose), dried milk protein ingredients, and dairy products. Our findings demonstrate that this model allows accurate description of postprandial glucose and insulin dynamics and provides insight into the physiological processes underlying meal responses. This model may facilitate the development of computational models that describe glucose homeostasis following the intake of multiple macronutrients, while capturing relevant features of an individual's metabolic health.

Elucidating yeast glycolytic dynamics at steady state growth and glucose pulses through kinetic metabolic modeling.

Microbial cell factories face changing environments during industrial fermentations. Kinetic metabolic models enable the simulation of the dynamic metabolic response to these perturbations, but their development is challenging due to model complexity and experimental data requirements. An example of this is the well-established microbial cell factory Saccharomyces cerevisiae, for which no consensus kinetic model of central metabolism has been developed and implemented in industry. Here, we aim to bring the academic and industrial communities closer to this consensus model. We developed a physiology informed kinetic model of yeast glycolysis connected to central carbon metabolism by including the effect of anabolic reactions precursors, mitochondria and the trehalose cycle. To parametrize such a large model, a parameter estimation pipeline was developed, consisting of a divide and conquer approach, supplemented with regularization and global optimization. Additionally, we show how this first mechanistic description of a growing yeast cell captures experimental dynamics at different growth rates and under a strong glucose perturbation, is robust to parametric uncertainty and explains the contribution of the different pathways in the network. Such a comprehensive model could not have been developed without using steady state and glucose perturbation data sets. The resulting metabolic reconstruction and parameter estimation pipeline can be applied in the future to study other industrially-relevant scenarios. We show this by generating a hybrid CFD-metabolic model to explore intracellular glycolytic dynamics for the first time. The model suggests that all intracellular metabolites oscillate within a physiological range, except carbon storage metabolism, which is sensitive to the extracellular environment.

The Accuracy of Wrist-Worn Photoplethysmogram-Measured Heart and Respiratory Rates in Abdominal Surgery Patients: Observational Prospective Clinical Validation Study.

BACKGROUND: Postoperative deterioration is often preceded by abnormal vital parameters. Therefore, vital parameters of postoperative patients are routinely measured by nursing staff. Wrist-worn sensors could potentially provide an alternative tool for the measurement of vital parameters in low-acuity settings. These devices would allow more frequent or even continuous measurements of vital parameters without relying on time-consuming manual measurements, provided their accuracy in this clinical population is established. OBJECTIVE: This study aimed to assess the accuracy of heart rate (HR) and respiratory rate (RR) measures obtained via a wearable photoplethysmography (PPG) wristband in a cohort of postoperative patients. METHODS: The accuracy of the wrist-worn PPG sensor was assessed in 62 post-abdominal surgery patients (mean age 55, SD 15 years; median BMI 34, IQR 25-40 kg/m2). The wearable obtained HR and RR measurements were compared to those of the reference monitor in the postanesthesia or intensive care unit. Bland-Altman and Clarke error grid analyses were performed to determine agreement and clinical accuracy. RESULTS: Data were collected for a median of 1.2 hours per patient. With a coverage of 94% for HR and 34% for RR, the device was able to provide accurate measurements for the large majority of the measurements as 98% and 93% of the measurements were within 5 bpm or 3 rpm of the reference signal. Additionally, 100% of the HR and 98% of the RR measurements were clinically acceptable on Clarke error grid analysis. CONCLUSIONS: The wrist-worn PPG device is able to provide measurements of HR and RR that can be seen as sufficiently accurate for clinical applications. Considering the coverage, the device was able to continuously monitor HR and report RR when measurements of sufficient quality were obtained. TRIAL REGISTRATION: ClinicalTrials.gov NCT03923127; https://www.clinicaltrials.gov/ct2/show/NCT03923127.

Using Kinetic Modelling to Infer Adaptations in Saccharomyces cerevisiae Carbohydrate Storage Metabolism to Dynamic Substrate Conditions.

Microbial metabolism is strongly dependent on the environmental conditions. While these can be well controlled under laboratory conditions, large-scale bioreactors are characterized by inhomogeneities and consequently dynamic conditions for the organisms. How Saccharomyces cerevisiae response to frequent perturbations in industrial bioreactors is still not understood mechanistically. To study the adjustments to prolonged dynamic conditions, we used published repeated substrate perturbation regime experimental data, extended it with proteomic measurements and used both for modelling approaches. Multiple types of data were combined; including quantitative metabolome, 13C enrichment and flux quantification data. Kinetic metabolic modelling was applied to study the relevant intracellular metabolic response dynamics. An existing model of yeast central carbon metabolism was extended, and different subsets of enzymatic kinetic constants were estimated. A novel parameter estimation pipeline based on combinatorial enzyme selection supplemented by regularization was developed to identify and predict the minimum enzyme and parameter adjustments from steady-state to dynamic substrate conditions. This approach predicted proteomic changes in hexose transport and phosphorylation reactions, which were additionally confirmed by proteome measurements. Nevertheless, the modelling also hints at a yet unknown kinetic or regulation phenomenon. Some intracellular fluxes could not be reproduced by mechanistic rate laws, including hexose transport and intracellular trehalase activity during substrate perturbation cycles.

Prognostic Value of Combined Biomarkers in Patients With Heart Failure: The Heartmarker Score.

Background: Heart failure (HF) biomarkers have prognostic value. The aim of this study was to combine HF biomarkers into an objective classification system for risk stratification of patients with HF. Methods: HF biomarkers were analyzed in a population of HF outpatients and expressed relative to their cut-off values (N-terminal pro-B-type natriuretic peptide [NT-proBNP] >1,000 pg/mL, soluble suppression of tumorigenesis-2 [ST2] >35 ng/mL, growth differentiation factor-15 [GDF-15] >2,000 pg/mL, and fibroblast growth factor-23 [FGF-23] >95.4 pg/mL). Biomarkers that remained significant in multivariable analysis were combined to devise the Heartmarker score. The performance of the Heartmarker score was compared to the widely used New York Heart Association (NYHA) classification based on symptoms during ordinary activity. Results: HF biomarkers of 245 patients were analyzed, 45 (18%) of whom experienced the composite endpoint of HF hospitalization, appropriate implantable cardioverter-defibrillator shock, or death. HF biomarkers were elevated more often in patients that reached the composite endpoint than in patients that did not reach the endpoint. NT-proBNP, ST2, and GDF-15 were independent predictors of the composite endpoint and were thus combined as the Heartmarker score. The event-free survival and distance covered in 6 minutes of walking decreased with an increasing Heartmarker score. Compared with the NYHA classification, the Heartmarker score was better at discriminating between different risk classes and had a comparable relationship to functional capacity. Conclusions: The Heartmarker score is a reproducible and intuitive model for risk stratification of outpatients with HF, using routine biomarker measurements.

A wearable patch based remote early warning score (REWS) in major abdominal cancer surgery patients.

INTRODUCTION: The shift toward remote patient monitoring methods to detect clinical deterioration requires testing of wearable devices in real-life clinical settings. This study aimed to develop a remote early warning scoring (REWS) system based on continuous measurements using a wearable device, and compare its diagnostic performance for the detection of deterioration to the diagnostic performance of the conventional modified early warning score (MEWS). MATERIALS AND METHODS: The study population of this prospective, single center trial consisted of patients who underwent major abdominal cancer surgery and were monitored using routine in-hospital spotcheck measurements of the vital parameters. Heart and respiratory rates were measured continuously using a wireless accelerometer patch (HealthDot). The prediction by MEWS of deterioration toward a complication graded Clavien-Dindo of 2 or higher was compared to the REWS derived from continuous measurements by the wearable patch. MAIN RESULTS: A total of 103 patients and 1909 spot-check measurements were included in the analysis. Postoperative deterioration was observed in 29 patients. For both EWS systems, the sensitivity (MEWS: 0.20 95% CI: [0.13-0.29], REWS: 0.20 95% CI: [0.13-0.29]) and specificity (MEWS: 0.96 95% CI: [0.95-0.97], REWS: 0.96 95% CI: [0.95-0.97]) were assessed. CONCLUSIONS: The diagnostic value of the REWS method, based on continuous measurements of the heart and respiratory rates, is comparable to that of the MEWS in patients following major abdominal cancer surgery. The wearable patch could detect the same amount of deteriorations, without requiring manual spot check measurements.

A Systems Analysis of Phenotype Heterogeneity in APOE*3Leiden.CETP Mice Induced by Long-Term High-Fat High-Cholesterol Diet Feeding.

Within the human population, considerable variability exists between individuals in their susceptibility to develop obesity and dyslipidemia. In humans, this is thought to be caused by both genetic and environmental variation. APOE*3-Leiden.CETP mice, as part of an inbred mouse model in which mice develop the metabolic syndrome upon being fed a high-fat high-cholesterol diet, show large inter-individual variation in the parameters of the metabolic syndrome, despite a lack of genetic and environmental variation. In the present study, we set out to resolve what mechanisms could underlie this variation. We used measurements of glucose and lipid metabolism from a six-month longitudinal study on the development of the metabolic syndrome. Mice were classified as mice with either high plasma triglyceride (responders) or low plasma triglyceride (non-responders) at the baseline. Subsequently, we fitted the data to a dynamic computational model of whole-body glucose and lipid metabolism (MINGLeD) by making use of a hybrid modelling method called Adaptations in Parameter Trajectories (ADAPT). ADAPT integrates longitudinal data, and predicts how the parameters of the model must change through time in order to comply with the data and model constraints. To explain the phenotypic variation in plasma triglycerides, the ADAPT analysis suggested a decreased cholesterol absorption, higher energy expenditure and increased fecal fatty acid excretion in non-responders. While decreased cholesterol absorption and higher energy expenditure could not be confirmed, the experimental validation demonstrated that the non-responders were indeed characterized by increased fecal fatty acid excretion. Furthermore, the amount of fatty acids excreted strongly correlated with bile acid excretion, in particular deoxycholate. Since bile acids play an important role in the solubilization of lipids in the intestine, these results suggest that variation in bile acid homeostasis may in part drive the phenotypic variation in the APOE*3-Leiden.CETP mice.

Quantifying the contribution of triglycerides to metabolic resilience through the mixed meal model.

Despite the pivotal role played by elevated circulating triglyceride levels in the pathophysiology of cardio-metabolic diseases many of the indices used to quantify metabolic health focus on deviations in glucose and insulin alone. We present the Mixed Meal Model, a computational model describing the systemic interplay between triglycerides, free fatty acids, glucose, and insulin. We show that the Mixed Meal Model can capture deviations in the post-meal excursions of plasma glucose, insulin, and triglyceride that are indicative of features of metabolic resilience; quantifying insulin resistance and liver fat; validated by comparison to gold-standard measures. We also demonstrate that the Mixed Meal Model is generalizable, applying it to meals with diverse macro-nutrient compositions. In this way, by coupling triglycerides to the glucose-insulin system the Mixed Meal Model provides a more holistic assessment of metabolic resilience from meal response data, quantifying pre-clinical metabolic deteriorations that drive disease development in overweight and obesity.

Development and validation of an early warning score to identify COVID-19 in the emergency department based on routine laboratory tests: a multicentre case-control study.

OBJECTIVES: Identifying patients with a possible SARS-CoV-2 infection in the emergency department (ED) is challenging. Symptoms differ, incidence rates vary and test capacity may be limited. As PCR-testing all ED patients is neither feasible nor effective in most centres, a rapid, objective, low-cost early warning score to triage ED patients for a possible infection is developed. DESIGN: Case-control study. SETTING: Secondary and tertiary hospitals in the Netherlands. PARTICIPANTS: The study included patients presenting to the ED with venous blood sampling from July 2019 to July 2020 (n=10 417, 279 SARS-CoV-2-positive). The temporal validation cohort covered the period from July 2020 to October 2021 (n=14 080, 1093 SARS-CoV-2-positive). The external validation cohort consisted of patients presenting to the ED of three hospitals in the Netherlands (n=12 061, 652 SARS-CoV-2-positive). PRIMARY OUTCOME MEASURES: The primary outcome was one or more positive SARS-CoV-2 PCR test results within 1 day prior to or 1 week after ED presentation. RESULTS: The resulting 'CoLab-score' consists of 10 routine laboratory measurements and age. The score showed good discriminative ability (AUC: 0.930, 95% CI 0.909 to 0.945). The lowest CoLab-score had high sensitivity for COVID-19 (0.984, 95% CI 0.970 to 0.991; specificity: 0.411, 95% CI 0.285 to 0.520). Conversely, the highest score had high specificity (0.978, 95% CI 0.973 to 0.983; sensitivity: 0.608, 95% CI 0.522 to 0.685). The results were confirmed in temporal and external validation. CONCLUSIONS: The CoLab-score is based on routine laboratory measurements and is available within 1 hour after presentation. Depending on the prevalence, COVID-19 may be safely ruled out in over one-third of ED presentations. Highly suspect cases can be identified regardless of presenting symptoms. The CoLab-score is continuous, in contrast to the binary outcome of lateral flow testing, and can guide PCR testing and triage ED patients.

Left atrial reservoir strain as a predictor of cardiac outcome in patients with heart failure: the HaFaC cohort study.

BACKGROUND: The left atrium (LA) is a key player in the pathophysiology of systolic and diastolic heart failure (HF). Speckle tracking derived LA reservoir strain (LASr) can be used as a prognostic surrogate for elevated left ventricular filling pressure similar to NT-proBNP. The aim of the study is to investigate the correlation between LASr and NT-proBNP and its prognostic value with regards to the composite endpoint of HF hospitalization and all-cause mortality within 1 year. METHODS: Outpatients, sent to the echocardiography core lab because of HF, were enrolled into this study. Patients underwent a transthoracic echocardiographic examination, commercially available software was used to measure LASr. Blood samples were collected directly after the echocardiographic examination to determine NT-proBNP. RESULTS: We included 174 HF patients, 43% with reduced, 36% with mildly reduced, and 21% with preserved ejection fraction. The study population showed a strong inverse correlation between LASr and log-transformed NT-proBNP (r = - 0.75, p < 0.01). Compared to NT-proBNP, LASr predicts the endpoint with a comparable specificity (83% vs. 84%), however with a lower sensitivity (70% vs. 61%). CONCLUSION: LASr is inversely correlated with NT-proBNP and a good echocardiographic predictor for the composite endpoint of hospitalization and all-cause mortality in patients with HF. TRIAL REGISTRATION: https://www.trialregister.nl/trial/7268.

Kinetic Modeling of Saccharomyces cerevisiae Central Carbon Metabolism: Achievements, Limitations, and Opportunities.

Central carbon metabolism comprises the metabolic pathways in the cell that process nutrients into energy, building blocks and byproducts. To unravel the regulation of this network upon glucose perturbation, several metabolic models have been developed for the microorganism Saccharomyces cerevisiae. These dynamic representations have focused on glycolysis and answered multiple research questions, but no commonly applicable model has been presented. This review systematically evaluates the literature to describe the current advances, limitations, and opportunities. Different kinetic models have unraveled key kinetic glycolytic mechanisms. Nevertheless, some uncertainties regarding model topology and parameter values still limit the application to specific cases. Progressive improvements in experimental measurement technologies as well as advances in computational tools create new opportunities to further extend the model scale. Notably, models need to be made more complex to consider the multiple layers of glycolytic regulation and external physiological variables regulating the bioprocess, opening new possibilities for extrapolation and validation. Finally, the onset of new data representative of individual cells will cause these models to evolve from depicting an average cell in an industrial fermenter, to characterizing the heterogeneity of the population, opening new and unseen possibilities for industrial fermentation improvement.

Accuracy of vital parameters measured by a wearable patch following major abdominal cancer surgery.

INTRODUCTION: Recent advances in wearable technology allow for the development of wirelessly connected sensors to continuously measure vital parameters in the general ward or even at home. The present study assesses the accuracy of a wearable patch (Healthdot) for continuous monitoring of heartrate (HR) and respiration rate (RR). MATERIALS AND METHODS: The Healthdot measures HR and RR by means of chest accelerometry. The study population consisted of patients following major abdominal oncological surgery. The analysis focused on the agreement between HR and RR measured by the Healthdot and the gold standard patient monitor in the intensive and post-anesthesia care unit. RESULTS: For HR, a total of 112 h of measurements was collected in 26 patients. For RR, a total of 102 h of measurements was collected in 21 patients. On second to second analysis, 97% of the HR and 87% of the RR measurements were within 5 bpm and 3 rpm of the reference monitor. Assessment of 5-min averaged data resulted in 96% of the HR and 95% of the RR measurements within 5 bpm and 3 rpm of the reference monitor. A Clarke error grid analysis showed that 100% of the HR and 99.4% of the 5-min averaged data was clinically acceptable. CONCLUSION: The Healthdot accurately measured HR and RR in a cohort of patients recovering from major abdominal surgery, provided that good quality data was obtained. These results push the Healthdot forward as a clinically acceptable tool in low acuity settings for unobtrusive, automatic, wireless and continuous monitoring.

Simulating Metabolic Flexibility in Low Energy Expenditure Conditions Using Genome-Scale Metabolic Models.

Metabolic flexibility is the ability of an organism to adapt its energy source based on nutrient availability and energy requirements. In humans, this ability has been linked to cardio-metabolic health and healthy aging. Genome-scale metabolic models have been employed to simulate metabolic flexibility by computing the Respiratory Quotient (RQ), which is defined as the ratio of carbon dioxide produced to oxygen consumed, and varies between values of 0.7 for pure fat metabolism and 1.0 for pure carbohydrate metabolism. While the nutritional determinants of metabolic flexibility are known, the role of low energy expenditure and sedentary behavior in the development of metabolic inflexibility is less studied. In this study, we present a new description of metabolic flexibility in genome-scale metabolic models which accounts for energy expenditure, and we study the interactions between physical activity and nutrition in a set of patient-derived models of skeletal muscle metabolism in older adults. The simulations show that fuel choice is sensitive to ATP consumption rate in all models tested. The ability to adapt fuel utilization to energy demands is an intrinsic property of the metabolic network.