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BACKGROUND: The complex anatomical structure of the foot-ankle imposes challenges to accurately quantify detailed hindfoot kinematics and estimate musculoskeletal loading parameters. Most systems used to capture or estimate dynamic joint function oversimplify the anatomical structure by reducing its complexity. RESEARCH QUESTION: Can four dimensional computed tomography (4D CT) imaging in combination with an innovative foot manipulator capture in vivo hindfoot kinematics during a simulated stance phase of walking and can talocrural and subtalar articular joint mechanics be estimated based on a detailed in silico musculoskeletal foot-ankle model. METHODS: A foot manipulator imposed plantar/dorsiflexion and inversion/eversion representing a healthy stance phase of gait in 12 healthy participants while simultaneously acquiring 4D CT images. Participant-specific 3D hindfoot rotations and translations were calculated based on bone-specific anatomical coordinate systems. Articular cartilage contact area and contact pressure of the talocrural and subtalar joints were estimated using an extended foot-ankle model updated with an elastic foundation contact model upon prescribing the participant-specific rotations measured in the 4D CT measurement. RESULTS: Plantar/dorsiflexion predominantly occurred at the talocrural joint (RoM 15.9±3.9°), while inversion/eversion (RoM 5.9±3.9°) occurred mostly at the subtalar joint, with the contact area being larger at the subtalar than at the talocrural joint. Contact pressure was evenly distributed between the talocrural and subtalar joint at the beginning of the simulated stance phase but was then redistributed from the talocrural to the subtalar joint with increasing dorsiflexion. SIGNIFICANCE: In a clinical case study, the healthy participants were compared with four patients after surgically treaded intra-articular calcaneal fracture. The proposed workflow was able to detect small but meaningful differences in hindfoot kinematics and kinetics, indicative of remaining hindfoot pathomechanics that may influence the onset and progression of degenerative joint diseases.

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Knee arthroplasty technique is constantly evolving and the opportunity for surgeons to practice new techniques is currently highly dependent on the availability of cadaveric specimens requiring certified facilities. The high cost, limited supply, and heterogeneity of cadaveric specimens has increased the demand for synthetic training models, which are currently limited by a lack of biomechanical fidelity. Here, we aimed to design, manufacture, and experimentally validate a synthetic knee surgical training model which reproduces the flexion dependent varus-valgus (VV) and anterior-posterior (AP) mechanics of cadaveric knees, while maintaining anatomic accuracy. A probabilistic finite element modeling approach was employed to design physical models to exhibit passive cadaveric VV and AP mechanics. Seven synthetic models were manufactured and tested in a six-degree-of-freedom hexapod robot. Overall, the synthetic models exhibited cadaver-like VV and AP mechanics across a wide range of flexion angles with little variation between models. In the extended position, two models showed increased valgus rotation (<0.5°), and three models showed increased posterior tibial translation (<1.7 mm) when compared to the 95% confidence interval (CI) of cadaveric measurements. At full flexion, all models showed VV and AP mechanics within the 95% CI of cadaveric measurements. Given the repeatable mechanics exhibited, the knee models developed in this study can be used to reduce the current reliance on cadaveric specimens in surgical training.

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Dancers frequently perform jumps in the context of a prolonged, continuous dance piece. The purpose of this study is to explore the lower-extremity energetics in healthy dancers performing repetitive dance jumps (sautés) before and after typical dance-specific choreography. Lower-extremity kinetic data were collected from 14 healthy female dancers during a series of sautés performed before and after 3 minutes of dance. Percent contributions of the lower-extremity joints to the whole-limb mechanical energy expenditure during ground contact were calculated. The jumps performed at the beginning were compared with the jumps at the end of the dance choreography. Dancers maintained the jump rate and consistent whole-limb mechanical energy expenditure between the jump series. As expected, for both jump series, the sautés had greater relative energetic contribution from the ankle and knee as compared with lesser contribution from the hip and toe. However, we observed lesser contribution from the knee and greater contribution from the hip after a 3-minute dance. After performing typical dance choreography, the dancers demonstrated a distal to proximal redistribution of individual joints' contribution to whole-limb mechanical energy expenditure.

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Peripheral artery disease (PAD) is characterized by reduced blood flow to the extremities due to atherosclerosis. Studies report impaired gait mechanics in patients with lower extremity PAD. We hypothesized that revascularization surgery would improve gait mechanics when quantified by net lower limb joint work across the stance phase of walking. We performed gait analyses in 35 patients with PAD and 35 healthy, older adults. Patients with PAD performed a walking protocol prior to and six months following revascularization surgery. Healthy adults only took part in a single walking session. Lower limb joint powers were calculated using inverse dynamics and were integrated across early, middle, and late stance phases to determine the work performed during each phase (J kg-1). The work mechanical ratio between positive-producing and negative-producing phases of stance was calculated for each lower-limb joint. Self-selected walking speed significantly increased from 1.13 ± 0.2 ms-1 to 1.26 ± 0.18 ms-1 in patients following revascularization (p < 0.001). We observed a significant decrease in positive late stance work (p < 0.001) in conjunction with more negative work during early stance (p < 0.001) in patients following revascularization. Revascularization surgery led to faster walking without an increase in the ankle joint's mechanical ratio. Our results suggest faster walking was achieved via work done at the hip rather than the ankle. These findings suggest that additional therapies that facilitate the restoration of muscle, tissue, and nervous system damage caused by years of having reduced blood flow to the limbs might still be beneficial following revascularization.

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The long head biceps tendon (LHBT) is presumed a common source of shoulder joint pain and injury. Despite common LHBT pathologies, diagnosis and preferred treatment remain frequently debated. This Short Communication reports the development of a subject-specific finite element model of the shoulder joint based on one subject's 3D reconstructed anatomy and 3D in vivo kinematics recorded from bone-fixed electromagnetic sensors. The primary purpose of this study was to use the developed finite element model to investigate the LHBT mechanical environment during a typical shoulder motion of arm raising. Furthermore, this study aimed to assess the viability of material models derived from uniaxial tensile tests for accurate simulation of in vivo motion. The findings of our simulations indicate that the LHBT undergoes complex multidimensional deformations. As such, uniaxial material properties reported in the existing body of literature are not sufficient to simulate accurately the in vivo mechanical behavior of the LHBT. Further experimental tests on cadaveric specimens, such as biaxial tension and combinations of tension and torsion, are needed to describe fully the mechanical behavior of the LHBT and investigate its mechanisms of injury.

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Implant malalignment has been reported to be a primary reason for revision total knee arthroplasty (TKA). In addition, altered muscle coordination patterns are commonly observed in TKA patients, which is thought to alter knee contact loads. A comprehensive understanding of the influence of surgical implantation and muscle recruitment strategies on joint contact mechanics is crucial to improve surgical techniques, increase implant longevity, and inform rehabilitation protocols. In this study, a detailed musculoskeletal model with a 12 degrees of freedom knee was developed to represent a TKA subject from the CAMS-Knee datasets. Using motion capture and ground reaction force data, a level walking cycle was simulated and the joint movement and loading patterns were estimated using a novel technique for concurrent optimization of muscle activations and joint kinematics. In addition, over 12'000 Monte Carlo simulations were performed to predict knee contact mechanics during walking, considering numerous combinations of implant alignment and muscle activation scenarios. Validation of our baseline simulation showed good agreement between the model kinematics and loading patterns against the in vivo data. Our analyses reveal a considerable impact of implant alignment on the joint kinematics, while variation in muscle activation strategies mainly affects knee contact loading. Moreover, our results indicate that high knee compressive forces do not necessarily originate from extreme kinematics and vice versa. This study provides an improved understanding of the complex inter-relationships between loading and movement patterns resulting from different surgical implantation and muscle coordination strategies and presents a validated framework towards population-based modelling in TKA.

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Model reproducibility is a point of emphasis for the National Institutes of Health (NIH) and in science, broadly. As the use of computational modeling in biomechanics and orthopedics grows, so does the need to assess the reproducibility of modeling workflows and simulation predictions. The long-term goal of the KneeHub project is to understand the influence of potentially subjective decisions, thus the modeler's "art", on the reproducibility and predictive uncertainty of computational knee joint models. In this paper, we report on the model calibration phase of this project, during which five teams calibrated computational knee joint models of the same specimens from the same specimen-specific joint mechanics dataset. We investigated model calibration approaches and decisions, and compared calibration workflows and model outcomes among the teams. The selection of the calibration targets used in the calibration workflow differed greatly between the teams and was influenced by modeling decisions related to the representation of structures, and considerations for computational cost and implementation of optimization. While calibration improved model performance, differences in the postcalibration ligament properties and predicted kinematics were quantified and discussed in the context of modeling decisions. Even for teams with demonstrated expertise, model calibration is difficult to foresee and plan in detail, and the results of this study underscore the importance of identification and standardization of best practices for data sharing and calibration.

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This study aimed to determine the within- and between-session reliability of ankle mechanics and vertical ground reaction forces (vGRF) during jump landings in turned-out and parallel foot positions in professional ballet dancers. Twenty-four professional ballet dancers (men = 13, women = 11) attended two data collection sessions where they completed five maximal countermovement jumps in each foot position. The ankle joint mechanics and vGRF of the right limb were recorded via a seven-camera motion capture system and one force platform. Within- and between-session intraclass correlation coefficients (ICC), coefficients of variation (CV), standard error of measurement, and minimal detectable change were calculated for three-dimensional ankle excursion, peak ankle angle, ankle joint velocity, moment, and power, as well as peak landing vGRF, time to peak landing vGRF, loading rate, and jump height. Across both foot positions, within- (ICC: 0.17-0.96; CV: 1.4-82.3%) and between-session (ICC: 0.02-0.98; CV:1.3-57.1%) reliability ranged from poor to excellent, with ankle excursion, peak ankle angle, and jump height demonstrating the greatest ICC values (ICC: 0.65-0.96; CV: 1.4-57%). Jump landings in a turned-out foot position demonstrated better within-session reliability compared to a parallel position, however, no difference in between-session reliability across the foot positions was observed. Most ankle mechanics provide adequate between-session, but not within-session, reliability during jump landings in professional ballet dancers.

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Tibiofemoral geometry influences knee passive motion and understanding their relationship can provide insight into knee function and mechanisms of injury. However, the complexity of the geometric constraints has made characterizing the relationship challenging. The aim of this study was to determine the tibiofemoral bone geometries that explain the variation in passive motion using a partial least squares regression (PLSR) model. The PLSR model was developed for 29 healthy cadaver specimens (10 female, 19 male) with femur and tibia geometries retrieved from MRI images and six degree-of-freedom tibiofemoral kinematics determined during a flexion cycle with minimal medial pressure. The first 13 partial least squares (PLS) components explained 90% of the variation in the kinematics and accounted for 89% of the variation in geometry. The first three PLS components which shared geometric changes to particular surface congruencies of the tibial and femoral condyles explained the most amount of variation in the kinematics, primarily in anterior-posterior translation. Meanwhile, variations in femoral condyle width and the intercondylar space, tibia plateau size and conformity, and tibia eminences heights in PLS 2 and 4 explained the greatest amount of variation in internal-external rotation. PLS 4 exhibiting variation in overall size of the knee accounted for greatest amount of variation in geometry (50%) and had the greatest influence on the abduction-adduction motion and some on internal-external rotation but, overall, explained only a small proportion of the kinematics (10%). Elucidating the complex relationship between tibiofemoral bone geometry and passive kinematics may help personalize treatments for improved functional outcomes in patients.

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Micropipette users commonly experience problems in the hand and upper limbs. Mechanical factors are thought to contribute to osteoarthritis (OA) initiation and progression in the basilar thumb joint. Finite element analysis can be used to examine the effects of micropipette design on contact mechanics measures within the basilar thumb joint. This pilot study examined the effect of micropipette handle diameter (12 mm, 25 mm, and 40 mm) and the presence of a finger rest on contact area, contact force, and peak contact pressure in the basilar thumb joint. All contact mechanics measures decreased with increasing handle diameter with significant differences between the 12 mm diameter and the 40 mm diameter handles (contact area down about 30 mm2, contact force down about 15 N, and peak pressure down about 1 MPa). Decreasing contact mechanics measures with increasing diameter matched our expectations that contact measures would decrease with a more open grip. Contact mechanics measures were higher (p < 0.05) with a finger rest for contact area and force. We expected peak contact pressure and contact area to decrease with the presence of a finger rest. The unexpected outcome may have been due to non-randomized testing order and fatigue during testing.

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The purpose of this study was to quantify the contribution of the individual quadriceps muscles to patellar tracking. The individual and/or combined quadriceps muscles were activated in rabbits (n = 6) during computer-controlled flexion/extension of the knee. Three-dimensional patellar tracking was measured for the vastus lateralis, vastus medialis, and rectus femoris when activated alone and when activated simultaneously at different frequencies, producing a range of knee extensor torques. Patellar tracking changed substantially as a function of knee extensor torque and differed between muscles. Specifically, when all quadriceps muscles were activated simultaneously, the patella shifted more medially and proximally and rotated and tilted more medially compared with when vastus lateralis and rectus femoris were activated alone (P < .05), whereas vastus medialis activation alone produced a similar tracking pattern to that observed when all quadriceps muscles were activated simultaneously. Furthermore, patellar tracking for a given muscle condition shifted more medially and proximally and rotated and tilted more medially with increasing knee extensor torques across the entire range of knee joint angles. The authors conclude that patellar tracking depends crucially on knee extensor force/torque and that vastus medialis affects patellar tracking in a distinctly different way than vastus lateralis and rectus femoris, which produce similar tracking patterns.

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Individuals with a unilateral transtibial amputation (ITTA) often experience greater loading on the intact limb during running and stepping tasks compared to individuals without amputation. This study aimed to investigate the mechanics of load absorption in the intact limb of ITTA and determine if increased ground reaction forces (GRF) persist during a start-stop task which (i) controlled touch-down velocity and (ii) removed the requirement for on-going locomotion. Data were collected using a twelve-camera motion capture system with two Kistler force platforms. Variables were extracted during the final loading phase of a 2-step start-stop task. The intact limb of ITTA and the dominant limb of able-bodied controls were compared using independent t-tests and effect size analysis. ITTA showed lower knee flexion angles at touchdown (p = 0.007, g = -1.43), and peak vertical GRF (p = 0.01, g = -1.33) compared to control subjects. ITTA also exhibited less hip (p = 0.14, g = 0.76) and ankle (p = 0.002, g = 1.82) absorptive power at touchdown and at peak vertical GRF (hip: p = 0.01, g = 1.23; ankle: p = 0.05, g = 0.97). ITTA exhibited greater peak vertical GRF (p = 0.01, g = 1.30) and braking GRF (p = 0.05, g = -0.96) on the intact limb compared to the controls. Our results indicate altered joint mechanics through the intact limb of ITTA are independent of the touchdown conditions or the need for ongoing locomotion. These altered joint mechanics increased loading experienced by the intact limb. Further work should be conducted examining a variety of other dynamic movements to fully understand the involved mechanics, so that intervention studies can be developed to reduce the load experienced by ITTA.

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Behaviors we perform each day, such as manipulating an object or walking, require precise control of the interaction forces between our bodies and the environment. These forces are generated by muscle contractions, specified by the nervous system, and by joint mechanics, determined by the intrinsic properties of the musculoskeletal system. Depending on behavioral goals, joint mechanics might simplify or complicate control of movement by the nervous system. Whether humans can exploit joint mechanics to simplify neural control remains unclear. Here we evaluated if leveraging joint mechanics simplifies neural control by comparing performance in three tasks that required subjects to generate specified torques about the ankle during imposed sinusoidal movements; only one task required torques that could be generated by leveraging the intrinsic mechanics of the joint. The complexity of the neural control was assessed by subjects' perceived difficulty and the resultant task performance. We developed a novel approach that used continuous estimates of ankle impedance, a quantitative description of the joint mechanics, and measures of muscle activity to determine the mechanical and neural contributions to the net ankle torque generated in each task. We found that the torque resulting from changes in neural control was reduced when ankle impedance was consistent with the task being performed. Subjects perceived this task to be easier than those that were not consistent with the impedance of the ankle and were able to perform it with the highest level of consistency across repeated trials. These results demonstrate that leveraging the mechanical properties of a joint can simplify task completion and improve performance.

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Dislocation remains the leading indication for revision of total hip arthroplasty (THA). The objective of this study was to use a computational model to compare the overall resistance to both anterior and posterior dislocation for the available THA constructs commonly considered by surgeons attempting to produce a stable joint. Patient-specific musculoskeletal models of THA patients performing activities consistent with anterior and posterior dislocation were developed to calculate joint contact forces and joint positions used for simulations of dislocation in a finite element model of the implanted hip that included an experimentally calibrated hip capsule representation. Dislocations were then performed with consideration of offset using +5 and +9 offset, iteratively with three lipped liner variations in jump distance (10°, 15°, and 20° lips), a size 40 head, and a dual-mobility construct. Dislocation resistance was quantified as the moment required to dislocate the hip and the integral of the moment-flexion angle (dislocation energy). Increasing head diameter increased resistive moment on average for anterior and posterior dislocation by 22% relative to a neutral configuration. A lipped liner resulted in increases in the resistive moment to posterior dislocation of 9%, 19%, and 47% for 10°, 15°, and 20° lips, a sensitivity of approximately 2.8 Nm/mm of additional jump distance. A dual-mobility acetabular design resulted in an average 38% increase in resistive moment and 92% increase in dislocation energy for anterior and posterior dislocation. A quantitative understanding of tradeoffs in the dislocation risk inherent to THA construct options is valuable in supporting surgical decision making.

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Anterolateral capsule injury, often concomitant with anterior cruciate ligament (ACL) injuries, may result in high-grade rotatory instability. Lateral extraarticular tenodesis (LET) is sometimes added to ACL reconstruction to address this instability. However, LET is a non-anatomic procedure and concerns regarding increased tibiofemoral contact pressure and reduced internal rotation exist for some individuals which may be due to their tibiofemoral bony morphology. Therefore, the objective of this study was to analyze the effect of bony morphology on knee kinematic and contact pressure before and after anterolateral capsule injury and LET. A (1) 134-N anterior tibial load with 200-N axial compression and (2) a 7-Nm internal torque with a 200-N axial compression were applied to cadaveric knees (n = 8) using a 6 degree-of-freedom robotic testing system. Tibiofemoral bony morphology was captured with computed tomography scans and analyzed using 3D statistical shape modeling. Kinematics at each state were correlated with the results from the statistical shape model. Two femoral and three tibial modes of variation correlated with kinematic and contact pressure data before and after anterolateral capsule injury and LET. A decreased lateral tibial plateau elevation correlated with greater internal rotation and anterior tibial translation after anterolateral capsule deficiency and LET. Decreased notch width correlated with decreased contact area after anterolateral capsule deficiency and LET demonstrating it as a risk factor for ACL injury. The results of this study demonstrate that bony morphology if properly understood, could help improve the efficacy of LET procedures and that bony morphology has different effects after injury and repair.

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Biophysics is rarely mentioned as one of the most useful parts of dental and medical students' curricula. However, with the growing complexity of tools and methods used in diagnostics and therapy, the knowledge of their physical foundations becomes important and helps with choosing the optimal solutions for both, a patient and a doctor. The aim of the proposed activity is to develop students' intuition about simple physical models that help with understanding fundamental properties of temporomandibular joint (TMJ). A simple device, which allows for bite force measurement, is proposed. It is based on beam bending and a strain gauge Wheatstone bridge circuit mounted on two connected arms: the stiff one and the more elastic one. Linear regression is the only mathematical concept needed for understanding the physical background of the proposed activity. During the proposed activity-measuring of bite force for incisors, premolars, and molars-students are confronted with basic concepts, such as lever, torque, electrical circuit, calibration curve. By utilizing a simple idea, instead of a commercially available device, students can understand where the data come from. Proposed system delivers physiologically reasonable results.

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INTRODUCTION: Rocker profile shoes with a proximally placed apex are currently one of the most prescribed shoe modifications for treatment and prevention of lower leg deficits. Three geometrical rocker design parameters apex position (AP), apex angle (AA) and rocker radius (RR) influence both plantar pressure redistribution and kinetic and kinematic alterations of the lower leg. In addition, longitudinal bending stiffness (LBS) of the outsole influences these parameters as well. This study aims to investigate the effects of the LBS in combination with different forefoot radii of rocker shoes on kinematics and kinetics of the lower limb. METHODS: 10 participants walked in standard shoes and six experimental shoe conditions with high and low LBS and three different forefoot rocker radii with the same (proximal) AP and AA. Lower extremity kinematics and kinetics were collected while walking on an instrumented treadmill at preferred walking speed and analysed with a repeated measures ANOVA and Statistical Parametric Mapping (SPM) (α = .05; post hoc α = .05/6). RESULTS: SPM analyses revealed no significant differences for LBS and interaction LBS*RR for most research variables in terminal stance (ankle angle, ankle moment, ankle power, foot-to-horizontal angle, shank-to-vertical angle, external ankle moment, ground reaction force angle). A significant LBS effect was found for anterior-posterior position of the centre of pressure during pre-swing and peak ankle dorsiflexion angle. No relevant significant differences were found in spatio-temporal parameters and total work at the ankle between low and high LBS. CONCLUSION: This study showed that longitudinal bending stiffness does not affect the biomechanical working mechanism of rocker profile shoes as long as toe plantarflexion is restricted. Providing that the forefoot rocker radius supports at least a normal foot-to-horizontal angle at toe-off, there is no reason to increase sole stiffness to change ankle kinematics and kinetics.

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OBJECTIVES: To explore the effects of wearing compression garments on joint mechanics, soft tissue vibration and muscle activities during drop jumps. METHODS: Twelve healthy male athletes were recruited to execute drop jumps from heights of 30, 45 and 60 cm whilst wearing compression shorts (CS) and control shorts (CON). Sagittal plane kinematics, ground reaction forces, accelerations of the quadriceps femoris (QF), hamstrings (HM) and shoe heel-cup, and electromyography images of the rectus femoris (RF) and biceps femoris (BF) were collected. RESULTS: Compared with wearing CON, wearing CS significantly reduced the QF peak acceleration at 45 and 60 cm and the HM peak acceleration at 30 cm. Wearing CS significantly increased the damping coefficient for QF and HM at 60 cm compared with wearing CON. Moreover, the peak transmissibility when wearing CS was significantly lower than that when wearing CON for all soft tissue compartments and heights, except for QF at 30 cm. Wearing CS reduced the RF activity during the pre-, post-, and eccentric activations for all heights and concentric activations at 45 cm; it also reduced the BF activity during post- and eccentric activations at 30 and 60 cm, respectively. The hip and knee joint moments and power or jump height were unaffected by the garment type. CONCLUSION: Applying external compression can reduce soft tissue vibrations without compromising neuromuscular performance during strenuous physical activities that involve exposure to impact-induced vibrations.

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The patellofemoral joint plays a crucial mechanical role during walking and running. It increases the knee extensor mechanism's moment arm and reduces the knee extension muscle forces required to generate the extension moment that supports body weight, prevents knee buckling and propels the centre of mass. However, the mechanical implications of moment arm variation caused by patellofemoral and tibiofemoral motion remain unclear. We used a data-driven musculoskeletal model with a 12-degree-of-freedom knee to simulate the knee extension moment arm during walking and running. Using a geometric method to calculate the moment arm, we found smaller moment arms during running than during walking in the swing phase. Overall, knee flexion causes differences between running and walking moment arms as increased flexion causes a posterior shift in the tibiofemoral rotation axis and patella articulation with the distal femur. Moment arms were also affected by knee motion direction and best predicted by separating by direction instead of across the entire gait cycle. Furthermore, we found high inter-subject variation in the moment arm that was largely explained by out-of-plane motion. Our results are consistent with the concept that shorter moment arms increase the effective mechanical advantage of the knee and may contribute to increased running velocity.

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The relationship between three-dimensional shape and patellofemoral mechanics is complicated. The Wiberg patella classification is a method of distinguishing shape differences in the axial plane of the patella that can be used to connect shape differences to observed mechanics. This study uses the Wiberg patella classification to differentiate variance in a statistical shape model describing changes in patella morphology and height. We investigate how patella morphology influences force distribution within the patellofemoral joint. The Wiberg type I patella has a more symmetrical medial and lateral facet while the type III patella has a larger lateral facet compared to medial. The second principal component of the statistical shape model described shape variation that qualitatively resembled the different Wiberg patellas. We generated patellofemoral morphologies from the statistical shape model and integrated them into a musculoskeletal model with a twelve degrees-of-freedom knee. We simulated an overground walking trial with these morphologies and recorded patellofemoral mechanics and ligament forces. An increase in patellar ligament force corresponded with an increase in patella height. Wiberg type III patellas had a sharper patella apex which related to lower ratios of quadriceps tendon forces to patellar ligament forces. The change in pivot point of the patella affects the ratio of forces as well as the patellofemoral reaction force. This study provides a better understanding of how patella morphology affects fundamental patella mechanics which may help identify at-risk populations for pathology development.

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