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1.
Nat Commun ; 12(1): 3700, 2021 06 17.
Article in English | MEDLINE | ID: mdl-34140471

ABSTRACT

The relationship between detritivore diversity and decomposition can provide information on how biogeochemical cycles are affected by ongoing rates of extinction, but such evidence has come mostly from local studies and microcosm experiments. We conducted a globally distributed experiment (38 streams across 23 countries in 6 continents) using standardised methods to test the hypothesis that detritivore diversity enhances litter decomposition in streams, to establish the role of other characteristics of detritivore assemblages (abundance, biomass and body size), and to determine how patterns vary across realms, biomes and climates. We observed a positive relationship between diversity and decomposition, strongest in tropical areas, and a key role of abundance and biomass at higher latitudes. Our results suggest that litter decomposition might be altered by detritivore extinctions, particularly in tropical areas, where detritivore diversity is already relatively low and some environmental stressors particularly prevalent.


Subject(s)
Biota , Ecosystem , Rivers , Animals , Biodiversity , Biomass , Body Size , Chironomidae/physiology , Climate , Ephemeroptera/physiology , Insecta/physiology , Plant Leaves/chemistry , Rainforest , Rivers/chemistry , Rivers/microbiology , Rivers/parasitology , Rivers/virology , Tropical Climate , Tundra
2.
Sci Rep ; 11(1): 5389, 2021 03 08.
Article in English | MEDLINE | ID: mdl-33686128

ABSTRACT

Identifying the prevalence of degenerative spinal pathologies and relevant demographic risk factors is important for understanding spine injury risk, prevention, treatment, and outcome, and for distinguishing acute injuries from degenerative pathologies. Prevalence data in the literature are often based on small-scale studies focused on a single type of pathology. This study evaluates the prevalence of diagnosis of selected degenerative spinal pathology diagnoses using Medicare insurance claim data in the context of published smaller-scale studies. In addition, the data are used to evaluate whether the prevalence is affected by age, sex, diagnosed obesity, and the use of medical imaging. The Medicare Claims 5% Limited Data Set was queried to identify diagnoses of degenerative spinal pathologies. Unique patient diagnoses per year were further evaluated as a function of age, gender, and obesity diagnosis. Participants were also stratified by coding for radiological imaging accompanying each diagnosis. The overall prevalence of diagnosed spinal degenerative disease was 27.3% and increased with age. The prevalence of diagnosed disc disease was 2.7 times greater in those with radiology. The results demonstrate that degenerative findings in the spine are common, and, since asymptomatic individuals may not receive a diagnosis of degenerative conditions, this analysis likely underestimates the general prevalence of these conditions.


Subject(s)
Medicare , Spinal Diseases , Age Factors , Aged , Aged, 80 and over , Female , Humans , Insurance Claim Review , Male , Obesity/diagnostic imaging , Obesity/epidemiology , Prevalence , Risk Factors , Sex Factors , Spinal Diseases/diagnostic imaging , Spinal Diseases/epidemiology , United States
3.
Sci Adv ; 7(13)2021 03.
Article in English | MEDLINE | ID: mdl-33771867

ABSTRACT

Running waters contribute substantially to global carbon fluxes through decomposition of terrestrial plant litter by aquatic microorganisms and detritivores. Diversity of this litter may influence instream decomposition globally in ways that are not yet understood. We investigated latitudinal differences in decomposition of litter mixtures of low and high functional diversity in 40 streams on 6 continents and spanning 113° of latitude. Despite important variability in our dataset, we found latitudinal differences in the effect of litter functional diversity on decomposition, which we explained as evolutionary adaptations of litter-consuming detritivores to resource availability. Specifically, a balanced diet effect appears to operate at lower latitudes versus a resource concentration effect at higher latitudes. The latitudinal pattern indicates that loss of plant functional diversity will have different consequences on carbon fluxes across the globe, with greater repercussions likely at low latitudes.

4.
Exp Eye Res ; 186: 107706, 2019 09.
Article in English | MEDLINE | ID: mdl-31226338

ABSTRACT

Glaucoma is the leading cause of irreversible blindness worldwide. Recently, estrogen deficiencies caused by early menopause, alterations in estrogen signaling via mutations in estrogen receptors, and polymorphisms along estrogen metabolic pathways have all been linked to an increased risk of developing glaucoma. Here, we examined how menopause and age impact visual function and retinal structure in an experimental model of glaucoma. Young (3-4 months) and aged (9-10 months) female Brown Norway rats were divided into pre- and post-menopausal cohorts by surgically inducing menopause via ovariectomy (OVX). After six weeks, ocular hypertension (OHT) was induced unilaterally for a period of eight weeks. Four cohorts were successfully followed to eight weeks: young sham (n = 8), young OVX (n = 9), aged sham (n = 10), and aged OVX (n = 11) animals. Intraocular pressure (IOP) was monitored weekly in all groups. Prior to inducing OHT (baseline) and at four and eight weeks after inducing OHT, we assessed visual acuity via the optomotor response (OMR) and retinal structure using optical coherence tomography (OCT). OHT decreased the OMR in all cohorts. We found that spatial frequency thresholds decreased by 54% in OVX animals after OHT compared to sham animals after OHT, regardless of age (p < 0.001). We also found thinning of the retinal nerve fiber layer (RNFL) and loss of total retinal thickness after induction of OHT. Aged animals had more thinning of the RNFL and loss of total retinal thickness compared to young animals (p < 0.001). Overall, OHT caused significant changes in visual function and retinal structure. Observing that OVX in young and aged animals further decreased spatial frequency thresholds after OHT suggests that an estrogen deficiency may intensify visual impairment after OHT.


Subject(s)
Aging/physiology , Menopause/physiology , Retina , Animals , Female , Glaucoma , Intraocular Pressure/physiology , Rats , Retina/pathology , Retina/physiopathology , Visual Acuity/physiology
5.
Traffic Inj Prev ; 19(sup2): S133-S135, 2018.
Article in English | MEDLINE | ID: mdl-30841805

ABSTRACT

OBJECTIVE: Acceleration-based injury metrics can be useful for quantitatively evaluating risk of concussion (a form of mild traumatic brain injury, or mTBI) after automobile collisions, especially when objective medical findings may be negative, as in many cases of concussion. In the present study, head acceleration data were used to evaluate the risk of concussion or more serious head injury to the driver of an automobile that experiences a rear impact resulting in a forward change in velocity (delta-V) of 15.5 km/h (9.6 mph). METHODS: Data were collected from 34 Insurance Institute for Highway Safety (IIHS) rear impact sled tests conducted from 2009 through 2017 for driver seats from 10 passenger car models leading in U.S. sales in 2017. Resultant translational head acceleration data were used to compute the head injury criterion (HIC; HIC15, HIC36) and A-3ms (the 3-ms resultant acceleration criterion utilized by the European New Car Assessment Protocol and others), and maximum resultant translational acceleration (aT). Maximum resultant rotational acceleration (aR) was estimated based on Biofidelic Rear Impact Dummy (BioRID) data from Welch et al. ( 2010 ). RESULTS: No sled test included in the study resulted in a HIC15 value exceeding 55, a HIC36 value exceeding 85, A-3ms exceeding 28 g, aT exceeding 28 g, or estimated aR exceeding 1,400 rad/s2. These values are far below published automotive injury risk values (IARV) used to evaluate crashworthiness. Further, contemporary concussion risk curves place the HIC15, aT, aR, and paired combination of aT and aR sustained by the BioRID anthropomorphic test dummy (ATD) in the IIHS tests at a negligible risk of concussion (mTBI). CONCLUSIONS: The 15.5 km/h delta-V IIHS rear impact sled tests conducted between 2009 and 2017 for common passenger automobile driver seats resulted in injury metrics associated with minimal risk of concussion or more severe head injuries.


Subject(s)
Brain Concussion/prevention & control , Craniocerebral Trauma/prevention & control , Manikins , Seat Belts , Whiplash Injuries/prevention & control , Acceleration , Accidents, Traffic/statistics & numerical data , Automobiles , Biomechanical Phenomena , Equipment Design , Humans , Motor Vehicles/statistics & numerical data
6.
Methods Mol Biol ; 1695: 135-159, 2018.
Article in English | MEDLINE | ID: mdl-29190025

ABSTRACT

The stiffness of the sclera is important in several ocular disorders, and there is hence a need to quantify the biomechanical properties of this tissue. Here, we present two methods for measuring the stiffness of scleral ocular tissues: ocular compliance testing and digital image correlation strain mapping. In tandem with these approaches, we provide two methods to spatially quantify the anisotropic alignment of collagen fibers making up the sclera, using second harmonic generation microscopy and small-angle light scattering. Together, these approaches allow specimen-specific measurement of tissue stiffness and collagen alignment, which are key factors in determining how the eye responds to mechanical loads.


Subject(s)
Collagen/chemistry , Sclera/diagnostic imaging , Sclera/physiopathology , Animals , Anisotropy , Biomechanical Phenomena , Collagen/ultrastructure , Dynamic Light Scattering/instrumentation , Elasticity , Humans , Mice , Microscopy, Confocal/instrumentation , Rats , Sclera/chemistry , Sclera/metabolism
8.
J R Soc Interface ; 14(129)2017 04.
Article in English | MEDLINE | ID: mdl-28381643

ABSTRACT

The concept of scleral stiffening therapies has emerged as a novel theoretical approach for treating the ocular disorders glaucoma and myopia. Deformation of specific regions of the posterior eye is innately involved in the pathophysiology of these diseases, and thus targeted scleral stiffening could resist these changes and slow or prevent progression of these diseases. Here, we present the first systematic screen and direct comparison of the stiffening effect of small molecule collagen cross-linking agents in the posterior globe, namely using glyceraldehyde, genipin and methylglyoxal (also called pyruvaldehyde). To establish a dose-response relationship, we used inflation testing to simulate the effects of increasing intraocular pressure in freshly harvested rat eyes stiffened with multiple concentrations of each agent. We used digital image correlation to compute the mechanical strain in the tissue as a metric of stiffness, using a novel treatment paradigm for screening relative stiffening by incubating half of each eye in cross-linker and using the opposite half as an internal control. We identified the doses necessary to increase stiffness by approximately 100%, namely 30 mM for glyceraldehyde, 1 mM for genipin and 7 mM for methylglyoxal, and we also identified the range of stiffening it was possible to achieve with such agents. Such findings will inform development of in vivo studies of scleral stiffening to treat glaucoma and myopia.


Subject(s)
Collagen/drug effects , Cross-Linking Reagents/pharmacology , Sclera/drug effects , Animals , Collagen/chemistry , Dose-Response Relationship, Drug , Glyceraldehyde/pharmacology , Intraocular Pressure/drug effects , Iridoids/pharmacology , Pyruvaldehyde/pharmacology , Rats , Sclera/pathology
9.
Invest Ophthalmol Vis Sci ; 57(6): 2666-77, 2016 05 01.
Article in English | MEDLINE | ID: mdl-27183053

ABSTRACT

PURPOSE: Scleral stiffening has been proposed as a treatment for glaucoma to protect the lamina cribrosa (LC) from excessive intraocular pressure-induced deformation. Here we experimentally evaluated the effects of moderate stiffening of the peripapillary sclera on the deformation of the LC. METHODS: An annular sponge, saturated with 1.25% glutaraldehyde, was applied to the external surface of the peripapillary sclera for 5 minutes to stiffen the sclera. Tissue deformation was quantified in two groups of porcine eyes, using digital image correlation (DIC) or computed tomography imaging and digital volume correlation (DVC). In group A (n = 14), eyes were subjected to inflation testing before and after scleral stiffening. Digital image correlation was used to measure scleral deformation and quantify the magnitude of scleral stiffening. In group B (n = 5), the optic nerve head region was imaged using synchrotron radiation phase-contrast microcomputed tomography (PC µCT) at an isotropic spatial resolution of 3.2 µm. Digital volume correlation was used to compute the full-field three-dimensional deformation within the LC and evaluate the effects of peripapillary scleral cross-linking on LC biomechanics. RESULTS: On average, scleral treatment with glutaraldehyde caused a 34 ± 14% stiffening of the peripapillary sclera measured at 17 mm Hg and a 47 ± 12% decrease in the maximum tensile strain in the LC measured at 15 mm Hg. The reduction in LC strains was not due to cross-linking of the LC. CONCLUSIONS: Peripapillary scleral stiffening is effective at reducing the magnitude of biomechanical strains within the LC. Its potential and future utilization in glaucoma axonal neuroprotection requires further investigation.


Subject(s)
Glaucoma/complications , Intraocular Pressure/physiology , Optic Disk/pathology , Optic Nerve Diseases/physiopathology , Sclera/physiopathology , Animals , Biomechanical Phenomena , Disease Models, Animal , Glaucoma/diagnosis , Glaucoma/physiopathology , Models, Biological , Optic Nerve Diseases/diagnosis , Sclera/diagnostic imaging , Swine , X-Ray Microtomography
10.
IEEE Trans Med Imaging ; 35(4): 988-99, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26642429

ABSTRACT

The lamina cribrosa (LC) is a complex mesh-like tissue in the posterior eye. Its biomechanical environment is thought to play a major role in glaucoma, the second most common cause of blindness. Due to its small size and relative inaccessibility, high-resolution measurements of LC deformation, important in characterizing LC biomechanics, are challenging. Here we present a novel noninvasive imaging method, which enables measurement of the three-dimensional deformation of the LC caused by acute elevation of intraocular pressure (IOP). Posterior segments of porcine eyes were imaged using synchrotron radiation phase contrast micro-computed tomography (PC µCT) at IOPs between 6 and 37 mmHg. The complex trabecular architecture of the LC was reconstructed with an isotropic spatial resolution of 3.2 µm. Scans acquired at different IOPs were analyzed with digital volume correlation (DVC) to compute full-field deformation within the LC. IOP elevation caused substantial tensile, shearing and compressive devformation within the LC, with maximum tensile strains at 30 mmHg averaging 5.5%, and compressive strains reaching 20%. We conclude that PC µCT provides a novel high-resolution method for imaging the LC, and when combined with DVC, allows for full-field 3D measurement of ex vivo LC biomechanics at high spatial resolution.


Subject(s)
Imaging, Three-Dimensional/methods , Intraocular Pressure/physiology , X-Ray Microtomography/methods , Animals , Biomechanical Phenomena , Eye/diagnostic imaging , Eye/physiopathology , Swine
11.
J R Soc Interface ; 12(104): 20141009, 2015 Mar 06.
Article in English | MEDLINE | ID: mdl-25589572

ABSTRACT

The lamina cribrosa (LC) is a tissue in the posterior eye with a complex trabecular microstructure. This tissue is of great research interest, as it is likely the initial site of retinal ganglion cell axonal damage in glaucoma. Unfortunately, the LC is difficult to access experimentally, and thus imaging techniques in tandem with image processing have emerged as powerful tools to study the microstructure and biomechanics of this tissue. Here, we present a staining approach to enhance the contrast of the microstructure in micro-computed tomography (micro-CT) imaging as well as a comparison between tissues imaged with micro-CT and second harmonic generation (SHG) microscopy. We then apply a modified version of Frangi's vesselness filter to automatically segment the connective tissue beams of the LC and determine the orientation of each beam. This approach successfully segmented the beams of a porcine optic nerve head from micro-CT in three dimensions and SHG microscopy in two dimensions. As an application of this filter, we present finite-element modelling of the posterior eye that suggests that connective tissue volume fraction is the major driving factor of LC biomechanics. We conclude that segmentation with Frangi's filter is a powerful tool for future image-driven studies of LC biomechanics.


Subject(s)
Eye/diagnostic imaging , Eye/pathology , Ocular Physiological Phenomena , Retinal Ganglion Cells/metabolism , X-Ray Microtomography , Animals , Automation , Biomechanical Phenomena , Biophysical Phenomena , Connective Tissue/pathology , Contrast Media/chemistry , Finite Element Analysis , Glaucoma/diagnostic imaging , Glaucoma/physiopathology , Microscopy , Microscopy, Confocal , Optic Nerve , Radiographic Image Interpretation, Computer-Assisted , Stress, Mechanical , Swine
12.
PLoS One ; 9(11): e111785, 2014.
Article in English | MEDLINE | ID: mdl-25365517

ABSTRACT

OBJECTIVE: Although plaque erosion causes approximately 40% of all coronary thrombi and disproportionally affects women more than men, its mechanism is not well understood. The role of tissue mechanics in plaque rupture and regulation of mechanosensitive inflammatory proteins is well established, but their role in plaque erosion is unknown. Given obvious differences in morphology between plaque erosion and rupture, we hypothesized that inflammation in general as well as the association between local mechanical strain and inflammation known to exist in plaque rupture may not occur in plaque erosion. Therefore, our objective was to determine if similar mechanisms underlie plaque rupture and plaque erosion. METHODS AND RESULTS: We studied a total of 74 human coronary plaque specimens obtained at autopsy. Using lesion-specific computer modeling of solid mechanics, we calculated the stress and strain distribution for each plaque and determined if there were any relationships with markers of inflammation. Consistent with previous studies, inflammatory markers were positively associated with increasing strain in specimens with rupture and thin-cap fibroatheromas. Conversely, overall staining for inflammatory markers and apoptosis were significantly lower in erosion, and there was no relationship with mechanical strain. Samples with plaque erosion most closely resembled those with the stable phenotype of thick-cap fibroatheromas. CONCLUSIONS: In contrast to classic plaque rupture, plaque erosion was not associated with markers of inflammation and mechanical strain. These data suggest that plaque erosion is a distinct pathophysiological process with a different etiology and therefore raises the possibility that a different therapeutic approach may be required to prevent plaque erosion.


Subject(s)
Coronary Thrombosis , Coronary Vessels , Models, Cardiovascular , Plaque, Atherosclerotic , Sex Characteristics , Adult , Aged , Coronary Thrombosis/metabolism , Coronary Thrombosis/pathology , Coronary Thrombosis/physiopathology , Coronary Vessels/metabolism , Coronary Vessels/pathology , Coronary Vessels/physiopathology , Female , Humans , Inflammation , Male , Middle Aged , Plaque, Atherosclerotic/metabolism , Plaque, Atherosclerotic/pathology , Plaque, Atherosclerotic/physiopathology
13.
J Biomech Eng ; 136(2): 021005, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24356942

ABSTRACT

The posterior eye is a complex biomechanical structure. Delicate neural and vascular tissues of the retina, choroid, and optic nerve head that are critical for visual function are subjected to mechanical loading from intraocular pressure, intraocular and extraorbital muscles, and external forces on the eye. The surrounding sclera serves to counteract excessive deformation from these forces and thus to create a stable biomechanical environment for the ocular tissues. Additionally, the eye is a dynamic structure with connective tissue remodeling occurring as a result of aging and pathologies such as glaucoma and myopia. The material properties of these tissues and the distribution of stresses and strains in the posterior eye is an area of active research, relying on a combination of computational modeling, imaging, and biomechanical measurement approaches. Investigators are recognizing the increasing importance of the role of the collagen microstructure in these material properties and are undertaking microstructural measurements to drive microstructurally-informed models of ocular biomechanics. Here, we review notable findings and the consensus understanding on the biomechanics and microstructure of the posterior eye. Results from computational and numerical modeling studies and mechanical testing of ocular tissue are discussed. We conclude with some speculation as to future trends in this field.


Subject(s)
Eye Injuries/physiopathology , Glaucoma/physiopathology , Intraocular Pressure , Models, Biological , Myopia/physiopathology , Posterior Eye Segment/pathology , Posterior Eye Segment/physiopathology , Computer Simulation , Eye Injuries/pathology , Glaucoma/pathology , Humans , Models, Anatomic , Myopia/pathology
14.
Cardiovasc Eng Technol ; 4(4)2013 Dec.
Article in English | MEDLINE | ID: mdl-24223678

ABSTRACT

PURPOSE: We investigated whether local hemodynamics were associated with sites of plaque erosion and hypothesized that patients with plaque erosion have locally elevated WSS magnitude in regions where erosion has occurred. METHODS: We generated 3D, patient-specific models of coronary arteries from biplane angiographic images in 3 human patients with plaque erosion diagnosed by optical coherence tomography (OCT). Using computational fluid dynamics, we simulated pulsatile blood flow and calculated both wall shear stress (WSS) and oscillatory shear index (OSI). We also investigated anatomic features of plaque erosion sites by examining branching and local curvature in x-ray angiograms of barium-perfused autopsy hearts. RESULTS: Neither high nor low magnitudes of mean WSS were associated with sites of plaque erosion. OSI and local curvature were also not associated with erosion. Anatomically, 8 of 13 hearts had a nearby bifurcation upstream of the site of plaque erosion. CONCLUSIONS: This study provides preliminary evidence that neither hemodynamics nor anatomy are predictors of plaque erosion, based upon a very unique dataset. Our sample sizes are small, but this dataset suggests that high magnitudes of wall shear stress, one potential mechanism for inducing plaque erosion, are not necessary for erosion to occur.

15.
Am J Physiol Heart Circ Physiol ; 304(3): H473-86, 2013 Feb 01.
Article in English | MEDLINE | ID: mdl-23203971

ABSTRACT

Spontaneous plaque rupture in mouse models of atherosclerosis is controversial, although numerous studies have discussed so-called "vulnerable plaque" phenotypes in mice. We compared the morphology and biomechanics of two acute and one chronic murine model of atherosclerosis to human coronaries of the thin-cap fibroatheroma (TCFA) phenotype. Our acute models were apolipoprotein E-deficient (ApoE(-/-)) and LDL receptor-deficient (LDLr(-/-)) mice, both fed a high-fat diet for 8 wk with simultaneous infusion of angiotensin II (ANG II), and our chronic mouse model was the apolipoprotein E-deficient strain fed a regular chow diet for 1 yr. We found that the mouse plaques from all three models exhibited significant morphological differences from human TCFA plaques, including the plaque burden, plaque thickness, eccentricity, and amount of the vessel wall covered by lesion as well as significant differences in the relative composition of plaques. These morphological differences suggested that the distribution of solid mechanical stresses in the walls may differ as well. Using a finite-element analysis computational solid mechanics model, we computed the relative distribution of stresses in the walls of murine and human plaques and found that although human TCFA plaques have the highest stresses in the thin fibrous cap, murine lesions do not have such stress distributions. Instead, local maxima of stresses were on the media and adventitia, away from the plaque. Our results suggest that if plaque rupture is possible in mice, it may be driven by a different mechanism than mechanics.


Subject(s)
Atherosclerosis/pathology , Plaque, Atherosclerotic/pathology , Angiotensin II/pharmacology , Animals , Apolipoproteins E/genetics , Atherosclerosis/genetics , Biomechanical Phenomena , Calcinosis/pathology , Computer Simulation , Dietary Fats/toxicity , Humans , Image Processing, Computer-Assisted , Mice , Mice, Knockout , Models, Biological , Phenotype , Plaque, Atherosclerotic/genetics , Receptors, LDL/genetics , Receptors, LDL/physiology , Stress, Mechanical
16.
J Biomech Eng ; 134(5): 051001, 2012 May.
Article in English | MEDLINE | ID: mdl-22757489

ABSTRACT

Patient-specific computational fluid dynamics (CFD) is a powerful tool for researching the role of blood flow in disease processes. Modern clinical imaging technology such as MRI and CT can provide high resolution information about vessel geometry, but in many situations, patient-specific inlet velocity information is not available. In these situations, a simplified velocity profile must be selected. We studied how idealized inlet velocity profiles (blunt, parabolic, and Womersley flow) affect patient-specific CFD results when compared to simulations employing a "reference standard" of the patient's own measured velocity profile in the carotid bifurcation. To place the magnitude of these effects in context, we also investigated the effect of geometry and the use of subject-specific flow waveform on the CFD results. We quantified these differences by examining the pointwise percent error of the mean wall shear stress (WSS) and the oscillatory shear index (OSI) and by computing the intra-class correlation coefficient (ICC) between axial profiles of the mean WSS and OSI in the internal carotid artery bulb. The parabolic inlet velocity profile produced the most similar mean WSS and OSI to simulations employing the real patient-specific inlet velocity profile. However, anatomic variation in vessel geometry and the use of a nonpatient-specific flow waveform both affected the WSS and OSI results more than did the choice of inlet velocity profile. Although careful selection of boundary conditions is essential for all CFD analysis, accurate patient-specific geometry reconstruction and measurement of vessel flow rate waveform are more important than the choice of velocity profile. A parabolic velocity profile provided results most similar to the patient-specific velocity profile.


Subject(s)
Carotid Arteries/anatomy & histology , Carotid Arteries/physiology , Computer Simulation , Hemodynamics , Hydrodynamics , Carotid Arteries/diagnostic imaging , Humans , Magnetic Resonance Angiography , Middle Aged , Models, Anatomic , Pulsatile Flow , Radiography , Stress, Mechanical
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