Wearable sensors and machine learning algorithms are becoming a viable alternative for biomechanical analysis outside of the laboratory. The purpose of this work was to estimate gait events from ...inertial measurement units (IMUs) and utilize machine learning for the estimation of ground reaction force (GRF) waveforms. Sixteen healthy runners were recruited for this study, with varied running experience. Force sensing insoles were used to measure normal foot-shoe forces, providing a proxy for vertical GRF and a standard for the identification of gait events. Three IMUs were mounted on each participant, two bilaterally on the dorsal aspect of each foot and one clipped to the back of each participant's waistband, approximating their sacrum. Participants also wore a GPS watch to record elevation and velocity. A Bidirectional Long Short Term Memory Network (BD-LSTM) was used to estimate GRF waveforms from inertial waveforms. Gait event estimation from both IMU data and machine learning algorithms led to accurate estimations of contact time. The GRF magnitudes were generally underestimated by the machine learning algorithm when presented with data from a novel participant, especially at faster running speeds. This work demonstrated that estimation of GRF waveforms is feasible across a range of running velocities and at different grades in an uncontrolled environment.
Cancer treatments have evolved from indiscriminate cytotoxic agents to selective genome- and immune-targeted drugs that have transformed the outcomes of some malignancies
. Tumor complexity and ...heterogeneity suggest that the 'precision medicine' paradigm of cancer therapy requires treatment to be personalized to the individual patient
. To date, precision oncology trials have been based on molecular matching with predetermined monotherapies
. Several of these trials have been hindered by very low matching rates, often in the 5-10% range
, and low response rates. Low matching rates may be due to the use of limited gene panels, restrictive molecular matching algorithms, lack of drug availability, or the deterioration and death of end-stage patients before therapy can be implemented. We hypothesized that personalized treatment with combination therapies would improve outcomes in patients with refractory malignancies. As a first test of this concept, we implemented a cross-institutional prospective study (I-PREDICT, NCT02534675 ) that used tumor DNA sequencing and timely recommendations for individualized treatment with combination therapies. We found that administration of customized multidrug regimens was feasible, with 49% of consented patients receiving personalized treatment. Targeting of a larger fraction of identified molecular alterations, yielding a higher 'matching score', was correlated with significantly improved disease control rates, as well as longer progression-free and overall survival rates, compared to targeting of fewer somatic alterations. Our findings suggest that the current clinical trial paradigm for precision oncology, which pairs one driver mutation with one drug, may be optimized by treating molecularly complex and heterogeneous cancers with combinations of customized agents.
•Ankle joint played a dominant role in the stance phase of running.•Knee and hip joint were dominant in the swing phase of walking and running.•Running required higher ankle joint stiffness compared ...to walking.
Locomotion task and speed changes affect dynamic joint function. Walking and running require different coordination patterns of lower extremity joint mechanics. These coordination differences can result in measurable changes in kinematic and kinetic patterns. When locomotion speed changes, the functional role and movement strategy of each joint is altered. A deeper understanding of joint level mechanics and functional interactions will benefit rehabilitation programs and assistive device development. In this study, joint stiffness, joint mechanical work and power were assessed, as they relate to dynamic function of joints during locomotion. Ten young healthy subjects (5 males, 5 females) participated in a treadmill walking (0.8–2.0 m/s) and running (1.8–3.8 m/s) study. When running speed increased, the stiffness of all three joints tended to increase. The ankle joint played a dominant role during the stance phase of running, generating more positive work than the knee (p = .003) and hip (p = .0001). The knee and hip joint were more dominant in walking and running swing phase energy absorption and generation, respectively. When locomotion speeds increased, stance phase ankle positive work, swing phase knee negative work, and hip joint positive work tended to increase. These findings suggest that change of locomotion speed or task results in definitive changes to lower extremity joint level mechanics patterns.
Nature employs a variety of tactics to precisely time and execute the processes and mechanics of life, relying on sequential sense and response cascades to transduce signaling events over multiple ...length and time scales. Many of these tactics, such as the activation of a zymogen, involve the direct manipulation of a material by a stimulus. Similarly, effective therapeutics and diagnostics require the selective and efficient homing of material to specific tissues and biomolecular targets with appropriate temporal resolution. These systems must also avoid undesirable or toxic side effects and evade unwanted removal by endogenous clearing mechanisms. Nanoscale delivery vehicles have been developed to package materials with the hope of delivering them to select locations with rates of accumulation and clearance governed by an interplay between the carrier and its cargo. Many modern approaches to drug delivery have taken inspiration from natural activatable materials like zymogens, membrane proteins, and metabolites, whereby stimuli initiate transformations that are required for cargo release, prodrug activation, or selective transport. This Perspective describes key advances in the field of stimuli-responsive nanomaterials while highlighting some of the many challenges faced and opportunities for development. Major hurdles include the increasing need for powerful new tools and strategies for characterizing the dynamics, morphology, and behavior of advanced delivery systems in situ and the perennial problem of identifying truly specific and useful physical or molecular biomarkers that allow a material to autonomously distinguish diseased from normal tissue.
Progression of age can influence gait characteristics. Previous research has investigated lower extremity joint mechanics between young and elderly people in locomotion, however little is known about ...whether differences exist between young and middle age people. Ten young healthy subjects (22.8 ± 5.3 years) and ten middle age healthy subjects (50.7 ± 6.0 years) engaged in treadmill walking (from 0.8 to 2.0 m/s) and running (from 1.8 to 3.8 m/s). The middle age group had higher ankle plantar flexor moment angular impulse (p = 0.002), total support moment impulse (p = 0.016), and hip stance positive work (p = 0.029) across walking speeds. Additionally, the middle age group had higher knee flexion angle at ground contact in walking (p = 0.005) and running (p = 0.037). These findings indicate that moderate age affects changes in ankle and hip kinetic characteristics in walking, and knee kinematic patterns in both walking and running.
Zero-velocity assumption has been used for estimation of foot trajectory and stride length during running from the data of foot-mounted inertial measurement units (IMUs). Although the assumption ...provides a reasonable initialization for foot trajectory and stride length estimation, the other source of errors related to the IMU’s orientation still remains. The purpose of this study was to develop an improved foot trajectory and stride length estimation method for the level ground running based on the displacement of the foot. Seventy-nine runners performed running trials at 5 different paces and their running motions were captured using a motion capture system. The accelerations and angular velocities of left and right feet were measured with two IMUs mounted on the dorsum of each foot. In this study, foot trajectory and stride length were estimated using zero-velocity assumption with IMU data, and the orientation of IMU was estimated to calculate the mediolateral and vertical distance of the foot between two consecutive midstance events. Calculated foot trajectory and stride length were compared with motion capture data. The results show that the method used in this study can provide accurate estimation of foot trajectory and stride length for level ground running across a range of running speeds.
Advances in characterizing the neuropathology and functional dysconnectivity of depression and promising trials with emerging circuit-targeted and fast-onset therapeutics are providing unprecedented ...opportunities to gain deeper insight into the neurobiology of this devastating and pervasive disorder. Because of practical and ethical limitations to dissecting these mechanisms in humans, continued progress will critically depend on our ability to emulate aspects of depressive symptomatology and treatment response in nonhuman organisms. Although various experimental models are currently available, they often draw skepticism from both clinicians and basic research scientists. We review recent progress and highlight some of the best leads to diversify and improve discovery end points for preclinical depression research.
The development of lightweight portable sensors and algorithms for the identification of gait events at steady-state running speeds can be translated into the real-world environment. However, the ...output of these algorithms needs to be validated. The purpose of this study was to validate the identification of running gait events using data from Inertial Measurement Units (IMUs) in a semi-uncontrolled environment. Fifteen healthy runners were recruited for this study, with varied running experience and age. Force-sensing insoles measured normal foot-shoe forces and provided a standard for identification of gait events. Three IMUs were mounted to the participant, two bilaterally on the dorsal aspect of the foot and one clipped to the back of each participant’s waistband, approximating their sacrum. The identification of gait events from the foot-mounted IMU was more accurate than from the sacral-mounted IMU. At running speeds <3.57 m s−1, the sacral-mounted IMU identified contact duration as well as the foot-mounted IMU. However, at speeds >3.57 m s−1, the sacral-mounted IMU overestimated foot contact duration. This study demonstrates that at controlled paces over level ground, we can identify gait events and measure contact time across a range of running skill levels.
Postural control is one of the primary body functions for fall prevention. Unexpected perturbation-based balance training is effective for improving postural control. However, the effect of ...perturbation-based training using assistive devices on muscle activity and co-contraction for standing balance is still unclear. This training is also difficult to perform easily because it requires large instruments or expert guidance. The purpose of this study is to demonstrate the effect of perturbation-based balance training using a wearable balance training device (WBTD) on postural control. In this study, fourteen healthy young adult males were assigned to either a WBTD group or a sham group. In the intervention session, participants in the WBTD group were perturbed either left or right direction at random timing by the WBTD during tandem stance balance training. Participants in the Sham group did not receive external perturbation during tandem stance balance training. Before and after the intervention session, participants of both groups underwent unexpected lateral perturbation postural control testing (pre- and post-test). The normalized integral of electromyography (IEMG), co-contraction index (CCI), and center of pressure (COP) parameters were measured in the pre- and post-test. Experimental results showed that the WBTD group in the post-test significantly decreased left Gluteus Medius IEMG, CCI of both Gluteus Medius, and peak <inline-formula> <tex-math notation="LaTeX">\text {COP}_{\text {ML}} </tex-math></inline-formula> velocity, compared to those of the pre-test (<inline-formula> <tex-math notation="LaTeX">{p} \lt 0.001 </tex-math></inline-formula>, <inline-formula> <tex-math notation="LaTeX">{p} \,\, =0.024 </tex-math></inline-formula>, <inline-formula> <tex-math notation="LaTeX">{p} \,\, =0.031 </tex-math></inline-formula>, respectively). We conclude that balance training using WBTD could improve flexible postural control adjustment via cooperative muscle activation.
The purpose of this study was to compare a heuristic feature identification algorithm with output from the Beta Process Auto Regressive Hidden Markov Model (BP-AR-HMM) utilizing minimally sampled (≤ ...100 Hz) human locomotion data for identification of gait events prior to their occurrence. Data were collected from 16 participants (21-64 years) using a single gyroscopic sensor in an inertial measurement unit on the dorsum of the foot, across multiple locomotion modes, including level ground walking and running (across speeds 0.8 m s −1 - 3.0 m s −1 ), ramps and stairs. Identification of gait events, initial contact (IC) and toe off (TO) with the heuristic algorithm, was 94% across locomotion modes. The features identified prior to initial contact had a lead time of 186.32 ± 86.70 ms, while TO had a lead time of 63.96 ± 46.30 ms. The BP-AR-HMM identified features that indicated an impending IC and TO with 99% accuracy, with a lead time of 59.41 ± 54.41 ms for IC and 90.79 ± 35.51 ms for TO. These approaches are consistent in their identification of gait events and have the potential to be utilized for classification and prediction of locomotion mode.
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