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ItemDevelopment of a Comprehensive Integrated Platform for Translational Innovation in Pain Opioid Abuse Disorder and Overdose(Georgia Institute of Technology, 2022) Skolnick, JeffreyVideo summary of research project "Development of a Comprehensive Integrated Platform for Translational Innovation in Pain Opioid Abuse Disorder and Overdose"
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ItemDrug Discovery Accelerated by Computational Methods(Georgia Institute of Technology, 2013-04-30) Jorgensen, William L.Drug discovery is being pursued through computer-aided design, synthesis, biological assaying, and crystallography. Lead identification features de novo design with the ligand growing program BOMB or docking of commercial compound libraries. The cheminformatics program QikProp is applied to filter candidate molecules to ensure that they have drug-like properties. The focus of this lecture will be optimization of the resultant leads to yield potent inhibitors. Specifically, Monte Carlo/free-energy perturbation simulations are executed to identify the most promising choices for substituents on rings, heterocycles, and linking groups. The designed compounds are then synthesized and assayed. Successful application has been achieved for HIV reverse transcriptase, FGFR1 kinase, and human and Plasmodium falciparum macrophage migration inhibitory factor (MIF); micromolar leads have been rapidly advanced to low nanomolar or picomolar inhibitors.
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ItemRocker Profile Restores Leg Progression When Walking with Orthotic Ankle Constraint(Georgia Institute of Technology, 2013-04-19) Oludare, Simisola O.Rocker profiles are one of the most commonly prescribed therapeutic footwear modifications. Typically, they are used to allow lower limb forward progression when ankle and foot motion are restricted by mechanical constraint (i.e. lower limb orthosis) or clinical pathology (i.e. lower limb fracture). Although rocker profiles are commonly used, their design and performance have not been clearly described. To address this need, we studied the role of rocker profile footwear and its influence on lower limb forward progression when used in combination with an orthosis designed to constrain the ankle joint. We hypothesize that healthy subjects walking with unilateral ankle-foot orthosis footwear combination will elicit no difference in the shank forward progression compared to control (no ankle constraint) during stance phase (early, mid, late). The shank forward progression was quantified as the forward and vertical components of the acceleration. Analysis of constrained and unconstrained shank acceleration for three subjects revealed no difference during mid-stance, but showed differences during early and late stance. Although there are some differences in the shank acceleration when walking with and without ankle constraint, there is no notable gait deviation between the two conditions. This supports the notion that the rocker profile designed in our laboratory functions as a biomimetic ankle-foot complex that restores lower limb forward progression when the ankle is mechanically constrained by an orthosis.
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ItemUltrasound Analysis of Plantar Tissue Stiffness of Behavior Properties in the Midfoot(Georgia Institute of Technology, 2013-04-19) Kessler, Joshua ; Azzarelo, JosephFoot orthoses have been used for many years to treat various pathologies. While these orthoses can be effective, the mechanism of how plantar soft tissues and skeletal structures interface with the orthosis is not well understood. Studies have been conducted which examine tissue properties of the heel pad, including the use of ultrasound, but analysis of the midfoot is limited. This study aims to quantify displacement and stiffness of the plantar soft tissues of the midfoot under a known load through the use of ultrasonography in weight bearing and non- weight bearing conditions. Twenty -five subjects were recruited for the study ranging in age from 23-56 (Mean = 36.08) years old, consisting of 12 females and 13 males. Simple demographic information was recorded and a Foot Posture Index (FPI) examination was performed on all subjects. A force application apparatus was designed that utilizes a stepper-motor-driven linear actuator. The test set-up consisted of load cell mounted to the actuator which could drive an ultrasound transducer into the plantar surface of the midfoot to a maximum load of 40N. The results show plantar foot tissue stiffness exhibits a non-linear "toe" region at low force values, while increased force causes a shift to a linear stiffness profile. Midfoot plantar tissues are significantly stiffer in weight bearing conditions than in nonweight bearing conditions (p<0.05). Observations and measurements from ultrasound videos indicate that soft tissue between the skin and skeletal structure experiences greater change in compression in non-weight bearing. However, muscle tissue appears to have a greater change in deformation under non-weight bearing, while the connective tissue between skin and muscle display greater change in deformation under weight bearing conditions. The disparity in amount of deformation between tissues during different weight bearing conditions shows that stiffness properties in the foot are dynamic. The aim for future research is to develop a map of plantar soft tissue properties in all regions of the foot for clinical reference in selecting compatible orthotic interface materials.
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ItemThe Capstone Research Experience(Georgia Institute of Technology, 2013-04-19) Kogler, Géza F.
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ItemEngaging the Cortical Action Encoding System in Prosthesis Users by Limb-Matched Movement Imitation(Georgia Institute of Technology, 2013-04-19) Cusack, WilliamThe mirror neuron system (MNS) has been attributed to increased activation in motor-related cortical areas upon viewing of another's actions. Recent work suggests that limb movements that are similar in appearance to that of the viewer preferentially activate the MNS. It is unclear how this effect applies to amputee prosthesis users. Intact subjects and upper extremity amputees were recruited to view video demonstrations of tools being used by an intact actor and a prosthetic device user. Subjects were asked to pantomime the movement seen in the video while recording electroencephalography. Intact subjects showed equivalent left parietofrontal activity during imitation after watching intact or prosthetic arms. Likewise, when prosthesis users imitated prosthesis demonstrations typical left parietofrontal planning activation was observed. The amputee prosthesis users who imitated intact actors revealed deviations from this pattern, showing greater bilateral parietal and occipital planning and execution activity. We suggest that when prosthesis users imitate intact subjects. the greater bilateral parietal and occipital activation during planning and execution reflects unique visuospatial processing. This change may be required to imitate movements when limb states between the observed and observer do not match. The finding that prosthesis users imitating other prosthesis users showed typical left parietofrontal activation suggests that prosthesis users engage typical planning related activity when they are able to imitate other prosthesis users. This result has significant implications on rehabilitation, as standard therapy involves training with an intact physical therapist, which could necessitate abnormal planning mechanisms in amputees when learning to use their prosthetic device.
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ItemAdaptation of Step-to-Step Mechanical Work on Center of Mass during Split-belt Treadmill Walking(Georgia Institute of Technology, 2013-04-19) Cho, GloriaThe neuromechanical goal of locomotor adaptation in healthy human walking is largely unknown. Understanding how locomotor adaptation is achieved in the context of such a goal provides insight into gait deficits following musculoskeletal or neuromuscular impairment. The dynamic walking theory presents a mechanistic framework for legged locomotion using passive dynamics. Applying the theory to human gait. collision loss at heel strike is the greatest source of energy loss. In order to reduce collision loss. or negative mechanical work. the trail limb produces a pre-emptive impulse just before lead limb heel strike. increasing positive mechanical work. The dynamic walking theory has not yet been applied to locomotor adaptation. This project investigates the neuromechanical goal of locomotor adaptation through a dynamic walking approach. With two belts running at different speeds. the split-belt treadmill presents a unique environment has been used as an effective tool for examining adaptation. Consistent with the dynamic walking approach. we hypothesized that there would be a reduction of negative mechanical work on the center of mass coupled with an increase in positive work from early to late adaptation. Fourteen healthy young adults were asked to walk on a split-belt treadmill with both belts moving at the same speed (''tied'' condition) or at different speeds ("split-belt" condition). Baseline trials consisted of three different tied conditions with belts running at slow. middle. and fast speeds. The adaptation period involved subjects walking in the split-belt condition for ten minutes with one belt set at the slow speed and the other at the fast speed. Finally. subjects walked on the slow tied condition for the post-adaptation period. Ground reaction forces provided by AMTI force plates were imported to Matlab for analysis and calculation of mechanical work. The step-to-step work calculations were then categorized into two different step transitions: fast to slow and slow to fast. The fast to slow step transition indicate steps where the subjects' trail limb is on the fast belt and the lead limb is on the slow belt. Results show a significant reduction of negative work in addition to an increase in positive work for the fast to slow step transitions. while the slow to fast step transitions do not show significance. Results from this work offer insight into the neuromechanical goals of locomotion. This has implications for the development of targeted gait rehabilitation and evidence-based outcome measures.
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ItemOptimal Dorsal Strap Placement and Angulation to Resist Foot Displacements in Orthoses and Footwear. In Vitro Study(Georgia Institute of Technology, 2013-04-19) Conner, Kalyn ; Kogler, Géza F.A dorsal strap on a lower extremity orthosis (e.g., ankle foot orthosis) is one of the most common addition to a device to control foot motion. The aim of this study was to establish clinical guidelines that orthotists could target when determining the placement and angulation of a dorsal foot control strap in an orthosis. An in vitro experimental study was designed that simulated the movement of heel rise with respect to an orthosis. Cadaveric limbs (n=5) were mounted in a test fixture. where the first and second toes were affixed to the base via a plate and screw and a 111 N weight attached to a cable and pulley mechanism lifted the limb and foot vertically. A round aluminum bar (1.0 cm in diameter) attached to a load cell was used to measure the force applied to the foot, simulating the dorsal control strap function in an orthosis. Nine test conditions were evaluated. The force application points studied were oriented along the longitudinal axis of the foot starting proximally at the talus with a middle and distal location 2.0 cm apart respectively. Forces were measured at each of the three longitudinal axis locations at three angles (i.e. 75°, 90°, 105°). Results demonstrated that the more proximally positioned force application point had a lower measured force compared to a corresponding distally placed position (p<0.05). In addition. an acute angle (75°) force application point resulted in a higher force output compared to an obtuse angle (105°) force application (p<0.05). while the perpendicular and obtuse force application pOints were statistically similar. The data suggests that the optimal placement of a dorsal foot control strap should be proximally positioned and the angle of force application should be oriented perpendicular whilst erring to an obtuse angle for the most efficient orthotic control of foot movements in an orthosis.
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ItemDevelopment of a Technique to Quantify Stance Phase Kinematics in the Forefoot and Tibia(Georgia Institute of Technology, 2013-04-19) Spain, DavidLower limb orthoses are relatively common devices used to restore functional mobility to individuals with pathologies that afflict the foot and ankle complex. In some instances, the foot shell may have to extend distal to the metatarsophalangeal joints consequentially imposing undesirable perturbations for portions of the gait cycle. While the importance of stance phase movements and the function of third rocker are well appreciated, the literature is sparse on actual kinematic data describing forefoot and tibia movements during walking in each of the three anatomical planes. This topic area of study was selected as an appropriate area in which we could develop a kinematic measurement system suitable for clinical use. Three specific design metrics were established for the measurement system. The first was quantifying movements in the three anatomical planes as well as the timing of stance phase. The second metric was that the system be capable of collecting repeatable data kinetic and kinematic. The third and final metric was that the system possesses design features suitable for clinical use. Inertial Measurement Units (IMU's) were selected for motion capture to quantify forefoot and tibia movements. The IMU sensors were affixed to custom molded interface shells for the tibia and foot respectively. Force resistive sensors were placed on the plantar surface of the foot at the calcaneus and the first MTP joint, allowing third rocker to be accurately defined. Both measurement devices were synchronized so that all data output could be integrated and analyzed. To test the system we designed a fundamental study to evaluate the movements of the forefoot and tibia during terminal and pre-swing phases of gait. The results appear to support the concept of a forefoot rocker during barefoot walking but further reveal that the "rocker-like" motion is multi-planar in nature. As expected there was variability in the timing, magnitude, and duration of movement between different subjects in each of the three planes of motion. Ultimately the knowledge acquired from this line of research could prove useful in a clinical setting; allowing analysis of patients' gait patterns for more accurate interpretation of alignment and performance of lower limb orthoses and prostheses.
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ItemA Tale of Two Legs: Maintaining Dynamic Stability in A-P and M-L Directions in Persons with Unilateral Transtibial Limb Loss(Georgia Institute of Technology, 2013-04-19) Bolger, DarrenFalling remains a significant concern among individuals with lower limb loss. While recent years have seen major advances in prosthetic technology that have contributed to improvements in locomotor performance, gaps still remain to address impairments related to balance control. This is due to our limited understanding of the mechanisms involved in dynamic balance control among individuals with lower limb loss. The objective of this study was to characterize the dynamic balance control of individuals with transtibial limb loss (TILL) in response to unexpected support surface translations in 12 evenly distributed (0-3300) and randomly applied directions. We hypothesized that individuals with unilateral TILL would exhibit decreased dynamic balance control compared to matched controls. Dynamic balance control was quantified using stability margin, a metric that calculates the difference between peak center of pressure (COP) and peak center of mass (COM) displacements. A smaller stability margin is interpreted as an increased likelihood of losing balance. An increased stability margin (p=0.012) during lateral sway toward the prosthetic limb was identified for individuals with TILL (n=4) compared to controls (n=4). This increase was due to a larger cumulative COP displacement (p= 0.012) rather than a reduction in COM displacement. Additionally, while stability margin and cumulative COP displacement were the same between groups during forward sway; individual COP displacements in the intact leg of individuals with TILL were significantly larger than both the prosthetic leg (p<0.001) and control subjects (p=0.002). These findings demonstrate that the intact leg plays a substantial role in compensating for deficits in the dynamic response of the prosthetic limb during forward sway (posterior perturbations). During lateral perturbations that load the prosthetic limb, the results suggest that individuals with TILL are unable to modulate the COP response under that prosthetic foot. These findings may provide insight into prosthetic foot/ankle design and training strategies.