Department of Biomedical Engineering and Mechanics

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A collaboration between School of Biomedical Engineering and Sciences and the Department of Engineering Science and Mechanics to form the Department of Biomedical Engineering and Mechanics.

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2D or 3D? How cell motility measurements are conserved across dimensions in vitro and translate in vivo
Galarza, Sualyneth; Kim, Hyuna; Atay, Naciye; Peyton, Shelly R.; Munson, Jennifer M. (2019-11-19)
Cell motility is a critical aspect of several processes, such as wound healing and immunity; however, it is dysregulated in cancer. Current limitations of imaging tools make it difficult to study cell migration in vivo. To overcome this, and to identify drivers from the microenvironment that regulate cell migration, bioengineers have developed 2D (two-dimensional) and 3D (three-dimensional) tissue model systems in which to study cell motility in vitro, with the aim of mimicking elements of the environments in which cells move in vivo. However, there has been no systematic study to explicitly relate and compare cell motility measurements between these geometries or systems. Here, we provide such analysis on our own data, as well as across data in existing literature to understand whether, and which, metrics are conserved across systems. To our surprise, only one metric of cell movement on 2D surfaces significantly and positively correlates with cell migration in 3D environments (percent migrating cells), and cell invasion in 3D has a weak, negative correlation with glioblastoma invasion in vivo. Finally, to compare across complex model systems, in vivo data, and data from different labs, we suggest that groups report an effect size, a statistical tool that is most translatable across experiments and labs, when conducting experiments that affect cellular motility.
Ablation outcome of irreversible electroporation on potato monitored by impedance spectrum under multi-electrode system
Zhao, Yajun; Liu, Hongmei; Bhonsle, Suyashree P.; Wang, Yilin; Davalos, Rafael V.; Yao, Chenguo (2018-09-20)
Background Irreversible electroporation (IRE) therapy relies on pulsed electric fields to non-thermally ablate cancerous tissue. Methods for evaluating IRE ablation in situ are critical to assessing treatment outcome. Analyzing changes in tissue impedance caused by electroporation has been proposed as a method for quantifying IRE ablation. In this paper, we assess the hypothesis that irreversible electroporation ablation outcome can be monitored using the impedance change measured by the electrode pairs not in use, getting more information about the ablation size in different directions. Methods Using a square four-electrode configuration, the two diagonal electrodes were used to electroporate potato tissue. Next, the impedance changes, before and after treatment, were measured from different electrode pairs and the impedance information was extracted by fitting the data to an equivalent circuit model. Finally, we correlated the change of impedance from various electrode pairs to the ablation geometry through the use of fitted functions; then these functions were used to predict the ablation size and compared to the numerical simulation results. Results The change in impedance from the electrodes used to apply pulses is larger and has higher deviation than the other electrode pairs. The ablation size and the change in resistance in the circuit model correlate with various linear functions. The coefficients of determination for the three functions are 0.8121, 0.8188 and 0.8691, respectively, showing satisfactory agreement. The functions can well predict the ablation size under different pulse numbers, and in some directions it did even better than the numerical simulation method, which used different electric field thresholds for different pulse numbers. Conclusions The relative change in tissue impedance measured from the non-energized electrodes can be used to assess ablation size during treatment with IRE according to linear functions.
Acceleration Feedback-Based Active and Semi-Active Seismic Response Control of Rail-Counterweight Systems of Elevators
Singh, Rildova; Singh, Mahendra P. (Hindawi, 2005-01-01)
Based on the observations in the past earthquake events, the traction elevators in buildings are known to be vulnerable to earthquake induced ground motions. Among several components of an elevator, the counterweight being heaviest is also known to be more susceptible than others. The inertial effects of the counterweight can overstress the guide rails on which it moves. Here we investigate to use the well-known acceleration feedback-based active and semi-active control methods to reduce stresses in the rails. The only way a control action can be applied to a moving counterweight-rail system is through a mass damper placed in the plane of the counterweight. For this, a part of the counterweight mass can be configured as a mass damper attached to a small actuator for an active scheme or to a magneto-rheological damper for a semi-active scheme. A comprehensive numerical study is conducted to evaluate the effectiveness of the proposed configuration of control system. It is observed that the two control schemes are effective in reducing the stress response by about 20 to 25% and improve the system fragility over a good range of seismic intensities.
Acoustic Receptivity of a Boundary-Layer to Tollmien-Schlichting Waves Resulting From a Finite-Height Hump At Finite Reynolds-Numbers
Nayfeh, Ali H.; Ashour, O. N. (AIP Publishing, 1994-11-01)
The acoustic receptivity of a boundary layer to Tollmien-Schlichting (T-S) waves resulting from a finite-height hump at finite Reynolds numbers is investigated. The steady flow is calculated using an interacting boundary-layer (IBL) scheme that accounts for viscous/inviscid interactions. The unsteady flow is written as the sum of a Stokes wave and a traveling wave generated due to the interaction of the Stokes flow with the steady disturbance resulting from the hump. The traveling wave is governed by a set of nonhomogeneous equations, which is a generalization of the Orr-Sommerfeld equation. The solution of these nonhomogeneous equations is projected onto the quasiparallel eigenmode using the quasiparallel adjoint. This leads to a nonhomogeneous equation with variable coefficients governing the amplitude and phase of the T-S wave. Results are presented for the amplitude variation and the receptivity at finite Reynolds numbers. The results are in good agreement with the experimental results of Saric, Hoos, and Radeztsky [Boundary Layer Stability and Transition to Turbulence (ASME, New York, 1991), FED No. 114, pp. 17-22] for all tested hump heights at the two-tested sound pressure levels. Application of this paper's theory to small humps yields results that agree with those of Choudhari and Streett [Phys. Fluids A 4, 2495 (1992)]; and Crouch [Phys. Fluids A 4, 1408 (1992)]. Application of suction is shown to reduce the receptivity resulting from the hump.
Acoustic streaming in a waveguide with slowly varying height
Thompson, Charles (Acoustical Society of America, 1984-01-01)
An analysis of acoustic streaming in a two-dimensional waveguide having slowly varying height is presented. Special attention is paid to waveguides with cross sections that are small compared to the acoustic and/or wall wavelengths. It is shown that the dynamic behavior of the enclosed fluid can be parameterized by the values of three small parameters, ɛ, 1/S, and 1/R, where ɛ is the ratio of the typical duct height H₀ to the wall wavelength L₀, 1/S is the ratio of the typical oscillatory particle displacement U₀ to the typical duct height H₀ and 1/R is the ratio of the oscillatory boundary layer thickness lᵥ to the typical duct height H 0. An analytical solution describing the streaming flow in the duct is given in terms of a regular perturbation sequence in ɛ. It is shown that the oscillatory pressure must satisfy the lossy Webster horn equation to O(ɛ²) if the no slip boundary condition is to be satisfied. Outside the boundary layer it is shown that the time averaged slip velocity is the sum of two terms. The first term is proportional to the product of the incident and reflected wave amplitudes. The second term is proportional to the difference between the incident and reflected acoustic intensity of the wave. For small values of 1/S, 1/R, and ɛ the streaming solution given is shown to be valid until R/S 2 becomes of O(1).
Acoustic wave propagation in a circular cosh duct carrying a mean flow
Thompson, Charles; Sen, Rahul (Acoustical Society of America, 1987-09-01)
An analysis of acoustic wave propagation in a waveguide carrying an incompressible mean flow is presented. The radius of the waveguide is taken to vary slowly as a function of axial location. It is shown that the dynamic behavior of the enclosed fluid can be parametrized by the small parameter where is the ratio of the typical duct radius R 0 and the wall wavelength L 0. An analytical solution for the pressure field in the duct is given in terms of a regular perturbation expansion in The method of matched asymptotic expansions is used to evaluate the refractive effect of a thin mean-flow boundary layer on the acoustic pressure field. It is shown that in the case where the duct geometry conforms to that of a circular cosh duct the effect of higher-order turning points in the wave equation can be effectively handled by a closed-form solution that approximately solves the governing equations. The results of analysis are compared to those obtained using numerical methods. 1987 Acoustical Society of America
Acoustic waves in ducts with sinusoidally perturbed walls and mean flow
Nayfeh, Ali H. (Acoustical Society of America, 1975)
An analysis is presented of the propagation of acoustic waves in a hard-walled duct with sinusoidally perturbed walls and carrying mean flow. The results show that resonance occurs whenever the wavenumber of the wall undulations is approximately equal to the difference between the wavenumber of any two propagating modes. It is shown that neither of the resonating modes could exist in the duct without strongly exciting the other resonating mode.
Activation of bacterial channel MscL in mechanically stimulated droplet interface bilayers
Najem, Joseph S.; Dunlap, Myles D.; Rowe, Ian D.; Freeman, Eric C.; Grant, John Wallace; Sukharev, Sergei; Leo, Donald J. (Springer Nature, 2015-09-08)
MscL, a stretch-activated channel, saves bacteria experiencing hypo-osmotic shocks from lysis. Its high conductance and controllable activation makes it a strong candidate to serve as a transducer in stimuli-responsive biomolecular materials. Droplet interface bilayers (DIBs), flexible insulating scaffolds for such materials, can be used as a new platform for incorporation and activation of MscL. Here, we report the first reconstitution and activation of the low-threshold V23T mutant of MscL in a DIB as a response to axial compressions of the droplets. Gating occurs near maximum compression of both droplets where tension in the membrane is maximal. The observed 0.1-3 nS conductance levels correspond to the V23T-MscL sub-conductive and fully open states recorded in native bacterial membranes or liposomes. Geometrical analysis of droplets during compression indicates that both contact angle and total area of the water-oil interfaces contribute to the generation of tension in the bilayer. The measured expansion of the interfaces by 2.5% is predicted to generate a 4-6 mN/m tension in the bilayer, just sufficient for gating. This work clarifies the principles of interconversion between bulk and surface forces in the DIB, facilitates the measurements of fundamental membrane properties, and improves our understanding of MscL response to membrane tension.
Adaptive process control for achieving consistent particles' states in atmospheric plasma spray process
Guduri, B.; Cybulsky, Michael; Pickrell, Gary R.; Batra, Romesh C. (2021-02-08)
The coatings produced by an atmospheric plasma spray process (APSP) must be of uniform quality. However, the complexity of the process and the random introduction of noise variables such as fluctuations in the powder injection rate and the arc voltage make it difficult to control the coating quality that has been shown to depend upon mean values of powder particles' temperature and speed, collectively called mean particles' states (MPSs), just before they impact the substrate. Here, we use a science-based methodology to develop a stable and adaptive controller for achieving consistent MPSs and thereby decrease the manufacturing cost. We first identify inputs into the APSP that significantly affect the MPSs and then formulate a relationship between these two quantities. When the MPSs deviate from their desired values, the adaptive controller is shown to successfully adjust the input parameters to correct them. The performance of the controller is tested via numerical experiments using the software, LAVA-P, that has been shown to well simulate the APSP.
Adding four-dimensional data assimilation by analysis nudging to the Model for Prediction Across Scales – Atmosphere
Bullock, Orren Russell, Jr.; Foroutan, Hosein; Gilliam, Robert C.; Herwehe, Jerold A. (Copernicus Publications, 2018-07-16)
The Model for Prediction Across Scales – Atmosphere (MPAS-A) has been modified to allow fourdimensional data assimilation (FDDA) by the nudging of temperature, humidity, and wind toward target values predefined on the MPAS-A computational mesh. The addition of nudging allows MPAS-A to be used as a global-scale meteorological driver for retrospective air quality modeling. The technique of “analysis nudging” developed for the Penn State/National Center for Atmospheric Research (NCAR) Mesoscale Model, and later applied in the Weather Research and Forecasting model, is implemented in MPAS-A with adaptations for its polygonal Voronoi mesh. Reference fields generated from 1° x 1° National Centers for Environmental Prediction (NCEP) FNL (Final) Operational Global Analysis data were used to constrain MPAS-A simulations on a 92–25 km variable-resolution mesh with refinement centered over the contiguous United States. Test simulations were conducted for January and July 2013 with and without FDDA, and compared to reference fields and near-surface meteorological observations. The results demonstrate that MPAS-A with analysis nudging has high fidelity to the reference data while still maintaining conservation of mass as in the unmodified model. The results also show that application of FDDA constrains model errors relative to 2m temperature, 2m water vapor mixing ratio, and 10m wind speed such that they continue to be at or below the magnitudes found at the start of each test period.
The adhesion function of the sodium channel beta subunit (beta 1) contributes to cardiac action potential propagation
Veeraraghavan, Rengasayee; Hoeker, Gregory S.; Alvarez-Laviada, Anita; Hoagland, Daniel T.; Wan, Xiaoping; King, D. Ryan; Sanchez-Alonso, Jose; Chen, Chunling; Jourdan, L. Jane; Isom, Lori L.; Deschenes, Isabelle; Smith, James W.; Gorelik, Julia; Poelzing, Steven; Gourdie, Robert G. (2018-08-14)
Computational modeling indicates that cardiac conduction may involve ephaptic coupling - intercellular communication involving electrochemical signaling across narrow extracellular clefts between cardiomyocytes. We hypothesized that beta 1(SCN1B) - mediated adhesion scaffolds trans-activating Na(V)1.5 (SCN5A) channels within narrow (<30 nm) perinexal clefts adjacent to gap junctions (GJs), facilitating ephaptic coupling. Super-resolution imaging indicated preferential beta 1 localization at the perinexus, where it co-locates with Na(V)1.5. Smart patch clamp (SPC) indicated greater sodium current density (I-Na) at perinexi, relative to non-junctional sites. A novel, rationally designed peptide, beta adp1, potently and selectively inhibited beta 1-mediated adhesion, in electric cell-substrate impedance sensing studies. beta adp1 significantly widened perinexi in guinea pig ventricles, and selectively reduced perinexal I-Na, but not whole cell I-Na, in myocyte monolayers. In optical mapping studies, beta adp1 precipitated arrhythmogenic conduction slowing. In summary, beta 1-mediated adhesion at the perinexus facilitates action potential propagation between cardiomyocytes, and may represent a novel target for anti-arrhythmic therapies.
Adiabatic Following in Two-Photon Transition
Nayfeh, Munir H.; Nayfeh, Ali H. (American Physical Society, 1977-03-01)
The coherent interaction of two smoothly varying, near-resonant, two-photon pulses with a three-level system can be described by "two-photon damped Bloch equations" which are analogous to those for a one-photon transition in a two-level system except for the presence of a two-photon coupling and a frequency shift. These equations are solved for the cases γ1, γ2≪Ω, γ1=γ2, and γ2k2ε4Ω2, γ1≪Ω, where γ1 and γ2 are the atomic energy and phase relaxation widths, respectively, and Ω is the Rabi frequency. The leading contribution to the refractive index is intensity dependent, caused by the level shifts inherent in multiphoton processes; it includes a relaxation dependent part which is important at times shorter than γ−11. The second-order contributions depend on the square of the intensity and the time-integrated square of the intensity. The latter contribution, which is relaxation dependent, causes line asymmetry at the long-wavelength wing; it consists of a term proportional to γ2−γ1 and only important at early times and a term proportional to 2γ2−γ1.
Age-related strength loss affects non-stepping balance recovery
Koushyar, Hoda; Bieryla, Kathleen A.; Nussbaum, Maury A.; Madigan, Michael L. (Public Library of Science, 2019-01-18)
Aging is associated with a higher risk of falls, and an impaired ability to recover balance after a postural perturbation is an important contributing factor. In turn, this impaired recovery ability likely stems from age-related decrements in lower limb strength. The purpose of this study was to investigate the effects of age-related strength loss on non-stepping balance recovery capability after a perturbation while standing, without constraining movements to the ankle as in prior reports. Two experiments were conducted. In the first, five young adults (ages 20–30) and six community-dwelling older adults (ages 70–80) recovered their balance, without stepping, from a backward displacement of a support surface. Balance recovery capability was quantified as the maximal backward platform displacement that a subject could withstand without stepping. The maximal platform displacement was 27% smaller among the older group (11.8±2.1 cm) vs. the young group (16.2±2.6 cm). In the second experiment, forward dynamic simulations of a two-segment, rigid-body model were used to investigate the effects of manipulating strength in the hip extensors/flexors and ankle plantar flexors/dorsiflexors. In these, typical age-related reductions in strength were included. The model predicted lower maximal platform displacements with age-related reductions only in plantar flexion and hip flexion strength. These findings support the previously reported age-related loss of balance recovery ability, and an important role for plantar flexor strength in this ability. © 2019 Koushyar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Algebraically growing waves in ducts with sheared mean flow
Nayfeh, Ali H.; Telionis, Demetri P. (Acoustical Society of America, 1974)
Standing or traveling waves which vary algebraically with the axial distance in uniform ducts with sheared mean velocity profiles are investigated. The results show that such waves are not possible for ducts with uniform cross sections and fully developed mean flows.
Allele-specific methylation in the FADS genomic region in DNA from human saliva, CD4+ cells, and total leukocytes
Rahbar, Elaheh; Waits, Charlotte M. K.; Kirby, Edward H.; Miller, Leslie R.; Ainsworth, Hannah C.; Cui, Tao; Sergeant, Susan; Howard, Timothy D.; Langefeld, Carl D.; Chilton, Floyd H. (2018-04-06)
Background Genetic variants within the fatty acid desaturase (FADS) gene cluster (human Chr11) are important regulators of long-chain (LC) polyunsaturated fatty acid (PUFA) biosynthesis in the liver and consequently have been associated with circulating LC-PUFA levels. More recently, epigenetic modifications such as DNA methylation, particularly within the FADS cluster, have been shown to affect LC-PUFA levels. Our lab previously demonstrated strong associations of allele-specific methylation (ASM) between a single nucleotide polymorphism (SNP) rs174537 and CpG sites across the FADS region in human liver tissues. Given that epigenetic signatures are tissue-specific, we aimed to evaluate the methylation status and ASM associations between rs174537 and DNA methylation obtained from human saliva, CD4+ cells and total leukocytes derived from whole blood. The goals were to (1) determine if DNA methylation from these peripheral samples would display similar ASM trends as previously observed in human liver tissues and (2) evaluate the associations between DNA methylation and circulating LC-PUFAs. Results DNA methylation at six CpG sites spanning FADS1 and FADS2 promoter regions and a putative FADS enhancer region were determined in two Caucasian cohorts of healthy volunteers: leukocytes in cohort 1 (n = 89, median age = 43, 35% male) and saliva and CD4+ cells in cohort 2 (n = 32, median age = 41, 41% male). Significant ASM between rs174537 and DNA methylation at three CpG sites located in the FADS2 promoter region (i.e., chr11:61594865, chr11:61594876, chr11:61594907) and one CpG site in the putative enhancer region (chr11:61587979) were observed with leukocytes. In CD4+ cells, significant ASM was observed at CpG sites chr11:61594876 and chr11:61584894. Genotype at rs174537 was significantly associated with DNA methylation from leukocytes. Similar trends were observed with CD4+ cells, but not with saliva. DNA methylation from leukocytes and CD4+ cells also significantly correlated with circulating omega-6 LC-PUFAs. Conclusions We observed significant ASM between rs174537 and DNA methylation at key regulatory regions in the FADS region from leukocyte and CD4+ cells. DNA methylation from leukocytes also correlated with circulating omega-6 LC-PUFAs. These results support the use of peripheral whole blood samples, with leukocytes showing the most promise for future nutrigenomic studies evaluating epigenetic modifications affecting LC-PUFA biosynthesis in humans.
Analysis of 2-dimensional transient problems for linear elastic and piezoelectric structures using the consecutive-interpolation quadrilateral element (CQ4)
Tinh, Q. B.; Du, D. N.; Zhang, X.; Hirose, S.; Batra, Romesh C. (Elsevier, 2016-07-01)
Anti-Swing Control of Gantry and Tower Cranes Using Fuzzy and Time-Delayed Feedback with Friction Compensation
Omar, Hanafy M.; Nayfeh, Ali H. (Hindawi, 2005-01-01)
We designed a feedback controller to automate crane operations by controlling the load position and its swing. First, a PD tracking controller is designed to follow a prescribed trajectory. Then, another controller is added to the control loop to damp the load swing. The anti-swing controller is designed based on two techniques: a time-delayed feedback of the load swing angle and an anti-swing fuzzy logic controller (FLC). The rules of the FLC are generated by mapping the performance of the time-delayed feedback controller. The same mapping method used for generating the rules can be applied to mimic the performance of an expert operator. The control algorithms were designed for gantry cranes and then extended to tower cranes by considering the coupling between the translational and rotational motions. Experimental results show that the controller is effective in reducing load oscillations and transferring the load in a reasonable time. To experimentally validate the theory, we had to compensate for friction. To this end, we estimated the friction and then applied a control action to cancel it. The friction force was estimated by assuming a mathematical model and then estimating the model coefficients using an off-line identification technique, the method of least squares (LS).
Application of sub-micrometer vibrations to mitigate bacterial adhesion.
Paces, Will R.; Holmes, Hal R.; Vlaisavljevich, Eli; Snyder, Katherine L.; Tan, Ee Lim; Rajachar, Rupak M.; Ong, Keat Ghee (2014-03-11)
As a prominent concern regarding implantable devices, eliminating the threat of opportunistic bacterial infection represents a significant benefit to both patient health and device function. Current treatment options focus on chemical approaches to negate bacterial adhesion, however, these methods are in some ways limited. The scope of this study was to assess the efficacy of a novel means of modulating bacterial adhesion through the application of vibrations using magnetoelastic materials. Magnetoelastic materials possess unique magnetostrictive property that can convert a magnetic field stimulus into a mechanical deformation. In vitro experiments demonstrated that vibrational loads generated by the magnetoelastic materials significantly reduced the number of adherent bacteria on samples exposed to Escherichia coli, Staphylococcus epidermidis and Staphylococcus aureus suspensions. These experiments demonstrate that vibrational loads from magnetoelastic materials can be used as a post-deployment activated means to deter bacterial adhesion and device infection.
Arrival times for dissipative, nonlinear second-sound waves in solids
Tarkenton, G. M.; Cramer, Mark S. (American Physical Society, 1995-07-01)
We extend our original analysis begun in Tarkenton et al. [Phys. Rev. B 49, 11 794 (1994)] to include dissipative effects that are important in real cryogenic systems where nonlinear second sound exists. We present results concerning arrival times of thermal pulses propagated in cryogenic crystals, namely the behavior of the arrival times as a function of pulse amplitude. These arrival times show some surprising effects due to competing nonlinear terms: after decreasing with increasing amplitude, as one would expect, the arrival times start to lengthen due to nonlinear effects and finally saturate at a level slightly above the shortest arrival times. All these surprising effects arise from competing nonlinear terms in the expression for the wave speed. We finally relate these results to the experiment we proposed in our original paper.
Assessment of Blood Biomarker Profile After Acute Concussion During Combative Training Among US Military Cadets: A Prospective Study From the NCAA and US Department of Defense CARE Consortium
Giza, Christopher C.; McCrea, Michael A.; Huber, Daniel L.; Cameron, Kenneth L.; Houston, Megan N.; Jackson, Jonathan C.; McGinty, Gerald T.; Pasquina, Paul; Broglio, Steven P.; Brooks, M. Alison; DiFiori, John P.; Duma, Stefan M.; Harezlak, Jaroslaw; Goldman, Joshua T.; Guskiewicz, Kevin M.; McAllister, Thomas W.; McArthur, David; Meier, Timothy B.; Mihalik, Jason P.; Nelson, Lindsay D.; Rowson, Steven; Gill, Jessica M. (2021-02-22)
Importance Validation of protein biomarkers for concussion diagnosis and management in military combative training is important, as these injuries occur outside of traditional health care settings and are generally difficult to diagnose. Objective To investigate acute blood protein levels in military cadets after combative training-associated concussions. Design, Setting, and Participants This multicenter prospective case-control study was part of a larger cohort study conducted by the National Collegiate Athletic Association and the US Department of Defense Concussion Assessment Research and Education (CARE) Consortium from February 20, 2015, to May 31, 2018. The study was performed among cadets from 2 CARE Consortium Advanced Research Core sites: the US Military Academy at West Point and the US Air Force Academy. Cadets who incurred concussions during combative training (concussion group) were compared with cadets who participated in the same combative training exercises but did not incur concussions (contact-control group). Clinical measures and blood sample collection occurred at baseline, the acute postinjury point (<6 hours), the 24- to 48-hour postinjury point, the asymptomatic postinjury point (defined as the point at which the cadet reported being asymptomatic and began the return-to-activity protocol), and 7 days after return to activity. Biomarker levels and estimated mean differences in biomarker levels were natural log (ln) transformed to decrease the skewness of their distributions. Data were collected from August 1, 2016, to May 31, 2018, and analyses were conducted from March 1, 2019, to January 14, 2020. Exposure Concussion incurred during combative training. Main Outcomes and Measures Proteins examined included glial fibrillary acidic protein, ubiquitin C-terminal hydrolase-L1, neurofilament light chain, and tau. Quantification was conducted using a multiplex assay (Simoa; Quanterix Corp). Clinical measures included the Sport Concussion Assessment Tool-Third Edition symptom severity evaluation, the Standardized Assessment of Concussion, the Balance Error Scoring System, and the 18-item Brief Symptom Inventory. Results Among 103 military service academy cadets, 67 cadets incurred concussions during combative training, and 36 matched cadets who engaged in the same training exercises did not incur concussions. The mean (SD) age of cadets in the concussion group was 18.6 (1.3) years, and 40 cadets (59.7%) were male. The mean (SD) age of matched cadets in the contact-control group was 19.5 (1.3) years, and 25 cadets (69.4%) were male. Compared with cadets in the contact-control group, those in the concussion group had significant increases in glial fibrillary acidic protein (mean difference in ln values, 0.34; 95% CI, 0.18-0.50; P < .001) and ubiquitin C-terminal hydrolase-L1 (mean difference in ln values, 0.97; 95% CI, 0.44-1.50; P < .001) levels at the acute postinjury point. The glial fibrillary acidic protein level remained high in the concussion group compared with the contact-control group at the 24- to 48-hour postinjury point (mean difference in ln values, 0.22; 95% CI, 0.06-0.38; P = .007) and the asymptomatic postinjury point (mean difference in ln values, 0.21; 95% CI, 0.05-0.36; P = .01). The area under the curve for all biomarkers combined, which was used to differentiate cadets in the concussion and contact-control groups, was 0.80 (95% CI, 0.68-0.93; P < .001) at the acute postinjury point. Conclusions and Relevance This study's findings indicate that blood biomarkers have potential for use as research tools to better understand the pathobiological changes associated with concussion and to assist with injury identification and recovery from combative training-associated concussions among military service academy cadets. These results extend the previous findings of studies of collegiate athletes with sport-associated concussions.

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