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Accelerating Biomarker Discovery Through Electronic Health Records, Automated Biobanking, and Proteomics.
Wells QS, Gupta DK, Smith JG, Collins SP, Storrow AB, Ferguson J, Smith ML, Pulley JM, Collier S, Wang X, Roden DM, Gerszten RE, Wang TJ
(2019) J Am Coll Cardiol 73: 2195-2205
MeSH Terms: Academic Medical Centers, Acceleration, Aged, Automation, Biological Specimen Banks, Biomarkers, Cohort Studies, Electronic Health Records, Female, Heart Failure, Humans, Male, Middle Aged, Proportional Hazards Models, Prospective Studies, Proteomics, Reproducibility of Results, Risk Assessment, Sensitivity and Specificity, Thrombospondins
Show Abstract · Added March 3, 2020
BACKGROUND - Circulating biomarkers can facilitate diagnosis and risk stratification for complex conditions such as heart failure (HF). Newer molecular platforms can accelerate biomarker discovery, but they require significant resources for data and sample acquisition.
OBJECTIVES - The purpose of this study was to test a pragmatic biomarker discovery strategy integrating automated clinical biobanking with proteomics.
METHODS - Using the electronic health record, the authors identified patients with and without HF, retrieved their discarded plasma samples, and screened these specimens using a DNA aptamer-based proteomic platform (1,129 proteins). Candidate biomarkers were validated in 3 different prospective cohorts.
RESULTS - In an automated manner, plasma samples from 1,315 patients (31% with HF) were collected. Proteomic analysis of a 96-patient subset identified 9 candidate biomarkers (p < 4.42 × 10). Two proteins, angiopoietin-2 and thrombospondin-2, were associated with HF in 3 separate validation cohorts. In an emergency department-based registry of 852 dyspneic patients, the 2 biomarkers improved discrimination of acute HF compared with a clinical score (p < 0.0001) or clinical score plus B-type natriuretic peptide (p = 0.02). In a community-based cohort (n = 768), both biomarkers predicted incident HF independent of traditional risk factors and N-terminal pro-B-type natriuretic peptide (hazard ratio per SD increment: 1.35 [95% confidence interval: 1.14 to 1.61; p = 0.0007] for angiopoietin-2, and 1.37 [95% confidence interval: 1.06 to 1.79; p = 0.02] for thrombospondin-2). Among 30 advanced HF patients, concentrations of both biomarkers declined (80% to 84%) following cardiac transplant (p < 0.001 for both).
CONCLUSIONS - A novel strategy integrating electronic health records, discarded clinical specimens, and proteomics identified 2 biomarkers that robustly predict HF across diverse clinical settings. This approach could accelerate biomarker discovery for many diseases.
Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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2 Members
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20 MeSH Terms
Wing-pitching mechanism of hovering Ruby-throated hummingbirds.
Song J, Luo H, Hedrick TL
(2015) Bioinspir Biomim 10: 016007
MeSH Terms: Acceleration, Animals, Biological Clocks, Birds, Computer Simulation, Flight, Animal, Models, Biological, Oscillometry, Rheology, Wings, Animal
Show Abstract · Added February 12, 2015
In hovering flight, hummingbirds reverse the angle of attack of their wings through pitch reversal in order to generate aerodynamic lift during both downstroke and upstroke. In addition, the wings may pitch during translation to further enhance lift production. It is not yet clear whether these pitching motions are caused by the wing inertia or actuated through the musculoskeletal system. Here we perform a computational analysis of the pitching dynamics by incorporating the realistic wing kinematics to determine the inertial effects. The aerodynamic effect is also included using the pressure data from a previous three-dimensional computational fluid dynamics simulation of a hovering hummingbird. The results show that like many insects, pitch reversal of the hummingbird is, to a large degree, caused by the wing inertia. However, actuation power input at the root is needed in the beginning of pronation to initiate a fast pitch reversal and also in mid-downstroke to enable a nose-up pitching motion for lift enhancement. The muscles on the wing may not necessarily be activated for pitching of the distal section. Finally, power analysis of the flapping motion shows that there is no requirement for substantial elastic energy storage or energy absorption at the shoulder joint.
0 Communities
2 Members
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10 MeSH Terms
Evaluation of a multiple spin- and gradient-echo (SAGE) EPI acquisition with SENSE acceleration: applications for perfusion imaging in and outside the brain.
Skinner JT, Robison RK, Elder CP, Newton AT, Damon BM, Quarles CC
(2014) Magn Reson Imaging 32: 1171-80
MeSH Terms: Acceleration, Adult, Algorithms, Brain, Brain Neoplasms, Contrast Media, Echo-Planar Imaging, Female, Fourier Analysis, Glioma, Humans, Image Processing, Computer-Assisted, Leg, Magnetic Resonance Imaging, Male, Muscle, Skeletal, Muscles, Oxygen, Perfusion Imaging, Reperfusion, Software
Show Abstract · Added September 8, 2014
Perfusion-based changes in MR signal intensity can occur in response to the introduction of exogenous contrast agents and endogenous tissue properties (e.g. blood oxygenation). MR measurements aimed at capturing these changes often implement single-shot echo planar imaging (ssEPI). In recent years ssEPI readouts have been combined with parallel imaging (PI) to allow fast dynamic multi-slice imaging as well as the incorporation of multiple echoes. A multiple spin- and gradient-echo (SAGE) EPI acquisition has recently been developed to allow measurement of transverse relaxation rate (R2 and R2(*)) changes in dynamic susceptibility contrast (DSC)-MRI experiments in the brain. With SAGE EPI, the use of PI can influence image quality, temporal resolution, and achievable echo times. The effect of PI on dynamic SAGE measurements, however, has not been evaluated. In this work, a SAGE EPI acquisition utilizing SENSE PI and partial Fourier (PF) acceleration was developed and evaluated. Voxel-wise measures of R2 and R2(*) in healthy brain were compared using SAGE EPI and conventional non-EPI multiple echo acquisitions with varying SENSE and PF acceleration. A conservative SENSE factor of 2 with PF factor of 0.73 was found to provide accurate measures of R2 and R2(*) in white (WM) (rR2=[0.55-0.79], rR2*=[0.47-0.71]) and gray (GM) matter (rR2=[0.26-0.59], rR2*=[0.39-0.74]) across subjects. The combined use of SENSE and PF allowed the first dynamic SAGE EPI measurements in muscle, with a SENSE factor of 3 and PF factor of 0.6 providing reliable relaxation rate estimates when compared to multi-echo methods. Application of the optimized SAGE protocol in DSC-MRI of high-grade glioma patients provided T1 leakage-corrected estimates of CBV and CBF as well as mean vessel diameter (mVD) and simultaneous measures of DCE-MRI parameters K(trans) and ve. Likewise, application of SAGE in a muscle reperfusion model allowed dynamic measures of R2', a parameter that has been shown to correlate with muscle oxy-hemoglobin saturation.
Copyright © 2014 Elsevier Inc. All rights reserved.
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4 Members
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21 MeSH Terms
Standardizing accelerometer-based activity monitor calibration and output reporting.
Coolbaugh CL, Hawkins DA
(2014) J Appl Biomech 30: 594-7
MeSH Terms: Acceleration, Accelerometry, Calibration, Equipment Failure Analysis, Reference Standards, Reproducibility of Results, Sensitivity and Specificity, Transducers, United States
Show Abstract · Added September 15, 2014
Wearable accelerometer-based activity monitors (AMs) are used to estimate energy expenditure and ground reaction forces in free-living environments, but a lack of standardized calibration and data reporting methods limits their utility. The objectives of this study were to (1) design an inexpensive and easily reproducible AM testing system, (2) develop a standardized calibration method for accelerometer-based AMs, and (3) evaluate the utility of the system and accuracy of the calibration method. A centrifuge-type device was constructed to apply known accelerations (0-8g) to each sensitive axis of 30 custom and two commercial AMs. Accelerometer data were recorded and matrix algebra and a least squares solution were then used to determine a calibration matrix for the custom AMs to convert raw accelerometer output to units of g's. Accuracy was tested by comparing applied and calculated accelerations for custom and commercial AMs. AMs were accurate to within 4% of applied accelerations. The relatively inexpensive AM testing system (< $100) and calibration method has the potential to improve the sharing of AM data, the ability to compare data from different studies, and the accuracy of AM-based models to estimate various physiological and biomechanical quantities of interest in field-based assessments of physical activity.
0 Communities
1 Members
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9 MeSH Terms
Validation of accelerometer wear and nonwear time classification algorithm.
Choi L, Liu Z, Matthews CE, Buchowski MS
(2011) Med Sci Sports Exerc 43: 357-64
MeSH Terms: Acceleration, Adult, Aged, Algorithms, Body Weight, Female, Humans, Male, Middle Aged, Monitoring, Ambulatory, Motor Activity, Sedentary Behavior, Sports Equipment, Young Adult
Show Abstract · Added December 10, 2013
INTRODUCTION - the use of movement monitors (accelerometers) for measuring physical activity (PA) in intervention and population-based studies is becoming a standard methodology for the objective measurement of sedentary and active behaviors and for the validation of subjective PA self-reports. A vital step in PA measurement is the classification of daily time into accelerometer wear and nonwear intervals using its recordings (counts) and an accelerometer-specific algorithm.
PURPOSE - the purpose of this study was to validate and improve a commonly used algorithm for classifying accelerometer wear and nonwear time intervals using objective movement data obtained in the whole-room indirect calorimeter.
METHODS - we conducted a validation study of a wear or nonwear automatic algorithm using data obtained from 49 adults and 76 youth wearing accelerometers during a strictly monitored 24-h stay in a room calorimeter. The accelerometer wear and nonwear time classified by the algorithm was compared with actual wearing time. Potential improvements to the algorithm were examined using the minimum classification error as an optimization target.
RESULTS - the recommended elements in the new algorithm are as follows: 1) zero-count threshold during a nonwear time interval, 2) 90-min time window for consecutive zero or nonzero counts, and 3) allowance of 2-min interval of nonzero counts with the upstream or downstream 30-min consecutive zero-count window for detection of artifactual movements. Compared with the true wearing status, improvements to the algorithm decreased nonwear time misclassification during the waking and the 24-h periods (all P values < 0.001).
CONCLUSIONS - the accelerometer wear or nonwear time algorithm improvements may lead to more accurate estimation of time spent in sedentary and active behaviors.
1 Communities
1 Members
1 Resources
14 MeSH Terms
Accelerometer-measured physical activity in Chinese adults.
Peters TM, Moore SC, Xiang YB, Yang G, Shu XO, Ekelund U, Ji BT, Tan YT, Liu DK, Schatzkin A, Zheng W, Chow WH, Matthews CE, Leitzmann MF
(2010) Am J Prev Med 38: 583-91
MeSH Terms: Acceleration, Adult, Age Factors, Aged, China, Cohort Studies, Female, Humans, Life Style, Logistic Models, Male, Middle Aged, Monitoring, Physiologic, Motor Activity, Multivariate Analysis, Obesity, Prospective Studies, Smoking, Urban Population
Show Abstract · Added May 4, 2017
BACKGROUND - Following adoption of a Western lifestyle, China is experiencing a decline in physical activity levels, which is projected to contribute to future increases in the burden of chronic diseases.
PURPOSE - This study aims to target public health interventions and identify personal characteristics associated with physical activity and sedentary behavior in urban Chinese adults.
METHODS - In a sample of 576 men and women aged 40-74 years from Shanghai, multiple logistic regression was used to examine demographic, anthropometric, and lifestyle factors in relation to levels of physical activity and sedentary behavior assessed by Actigraph accelerometers.
RESULTS - Participants spent 317 minutes/day in physical activity and 509 minutes/day sedentary. In multivariate models, people aged > or =60 years were significantly less likely than those aged <50 years to engage in physical activity (OR=0.29, 95% CI=0.17, 0.49) and more likely to spend time sedentary (OR=2.77, 95% CI=1.53, 5.05). Similarly, obese individuals were less likely to be physically active (OR=0.34, 95% CI=0.17, 0.66) and they were suggestively more likely to be sedentary (OR=1.87, 95% CI=0.94, 3.71) than normal-weight individuals. Furthermore, current cigarette smokers were less physically active than those who formerly or never smoked (OR=0.47, 95% CI=0.28, 0.78).
CONCLUSIONS - Physical activity promotion programs in urban China should target older people, obese individuals, and cigarette smokers, as these population subgroups exhibited low levels of physical activity.
Published by Elsevier Inc.
0 Communities
1 Members
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19 MeSH Terms
Comparing the performance of three generations of ActiGraph accelerometers.
Rothney MP, Apker GA, Song Y, Chen KY
(2008) J Appl Physiol (1985) 105: 1091-7
MeSH Terms: Acceleration, Algorithms, Animals, Calibration, Energy Metabolism, Equipment Design, Humans, Materials Testing, Models, Biological, Monitoring, Ambulatory, Movement, Oscillometry, Reproducibility of Results
Show Abstract · Added March 10, 2014
ActiGraph accelerometers are a useful tool for objective assessment of physical activity in clinical and epidemiological studies. Several generations of ActiGraph are being used; however, little work has been done to verify that measurements are consistent across generations. This study employed mechanical oscillations to characterize the dynamic response and intermonitor variability of three generations of ActiGraph monitors, from the oldest 7164 (n = 13), 71256 (n = 12), to the newest GT1M (n = 12). The response due to independent radius (22.1-60.4 mm) and frequency (25-250 rpm) changes were measured, as well as intermonitor variability within each generation. The 7164 and 71256 have similar relationships between activity counts and radius (P = 0.229) but were significantly different from the GT1M (P < 0.001). The frequency responses were nonlinear in all three generations. Although the response curve shapes were similar, the differences between generations at various frequencies were significant (P < 0.017), especially in the extremes of the measurement range. Intermonitor variability was markedly reduced in the GT1M compared with the 7164 and 71256. Other measurement differences between generations include decreased peak counts and decreased sensitivity in low-frequency detection in the GT1M. The results of this study revealed an improvement of the intermonitor variability by the GT1M monitor. However, the reduced sensitivity in low-count ranges in the GT1M may not be well suited for monitoring sedentary or light-intensity movements. Furthermore, the algorithms for energy expenditure predictions developed using older 7164 monitors may need to be modified for the GT1M.
0 Communities
1 Members
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13 MeSH Terms
Artificial gravity: a possible countermeasure for post-flight orthostatic intolerance.
Moore ST, Diedrich A, Biaggioni I, Kaufmann H, Raphan T, Cohen B
(2005) Acta Astronaut 56: 867-76
MeSH Terms: Acceleration, Astronauts, Blood Pressure, Centrifugation, Fluid Shifts, Gravity, Altered, Heart Rate, Humans, Hypotension, Orthostatic, Otolithic Membrane, Reflex, Vestibulo-Ocular, Space Flight, Weightlessness, Weightlessness Countermeasures
Show Abstract · Added December 10, 2013
Four payload crewmembers were exposed to sustained linear acceleration in a centrifuge during the Neurolab (STS-90) flight. In contrast to previous studies, otolith-ocular reflexes were preserved during and after flight. This raised the possibility that artificial gravity may have acted as a countermeasure to the deconditioning of otolith-ocular reflexes. None of the astronauts who were centrifuged had orthostatic intolerance when tested with head-up passive tilt after flight. Thus, centrifugation may also have helped maintain post-flight hemodynamic responses to orthostasis by preserving the gain of the otolith-sympathetic reflex. A comparison with two fellow Neurolab orbiter crewmembers not exposed to artificial gravity provided some support for this hypothesis. One of the two had hemodynamic changes in response to post-flight tilt similar to orthostatically intolerant subjects from previous missions. More data is necessary to evaluate this hypothesis, but if it were proven correct, in-flight short-radius centrifugation may help counteract orthostatic intolerance after space flight.
c2005 Elsevier Ltd. All rights reserved.
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2 Members
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14 MeSH Terms
Vestibular control of sympathetic activity. An otolith-sympathetic reflex in humans.
Kaufmann H, Biaggioni I, Voustianiouk A, Diedrich A, Costa F, Clarke R, Gizzi M, Raphan T, Cohen B
(2002) Exp Brain Res 143: 463-9
MeSH Terms: Acceleration, Adolescent, Adrenergic Fibers, Adult, Blood Pressure, Female, Humans, Male, Otolithic Membrane, Posture, Reflex, Vestibulo-Ocular, Vestibular Function Tests
Show Abstract · Added December 10, 2013
It has been proposed that a vestibular reflex originating in the otolith organs and other body graviceptors modulates sympathetic activity during changes in posture with regard to gravity. To test this hypothesis, we selectively stimulated otolith and body graviceptors sinusoidally along different head axes in the coronal plane with off-vertical axis rotation (OVAR) and recorded sympathetic efferent activity in the peroneal nerve (muscle sympathetic nerve activity, MSNA), blood pressure, heart rate, and respiratory rate. All parameters were entrained during OVAR at the frequency of rotation, with MSNA increasing in nose-up positions during forward linear acceleration and decreasing when nose-down. MSNA was correlated closely with blood pressure when subjects were within +/-90 degrees of nose-down positions with a delay of 1.4 s, the normal latency of baroreflex-driven changes in MSNA. Thus, in the nose-down position, MSNA was probably driven by baroreflex afferents. In contrast, when subjects were within +/-45 degrees of the nose-up position, i.e., when positive linear acceleration was maximal along the naso-ocipital axis, MSNA was closely related to gravitational acceleration at a latency of 0.4 s. This delay is too short for MSNA changes to be mediated by the baroreflex, but it is compatible with the delay of a response originating in the vestibular system. We postulate that a vestibulosympathetic reflex, probably originating mainly in the otolith organs, contributes to blood pressure maintenance during forward linear acceleration. Because of its short latency, this reflex may be one of the earliest mechanisms to sustain blood pressure upon standing.
0 Communities
1 Members
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12 MeSH Terms
Autonomic neuropharmacology.
Robertson D
(1993) Curr Opin Neurol Neurosurg 6: 527-30
MeSH Terms: Acceleration, Autonomic Nervous System, Autonomic Nervous System Diseases, Humans, Neurotransmitter Agents, Sympatholytics, Sympathomimetics, Synaptic Transmission, Syncope, Weightlessness
Show Abstract · Added December 10, 2013
In the past year, improvements have occurred in our understanding of the pathophysiology and management of autonomic disorders and syncope. There has also been improved understanding of the autonomic role in the physiology of weightlessness.
0 Communities
1 Members
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10 MeSH Terms