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Abstract Understanding individuals’ distinct movement patterns is crucial for health, rehabilitation, and sports. Recently, we developed a machine learning-based framework to show that “gait signatures” describing the neuromechanical dynamics governing able-bodied and post-stroke gait kinematics remain individual-specific across speeds. However, we only evaluated gait signatures within a limited speed range and number of participants, using only sagittal plane (i.e., 2D) joint angles. Here we characterized changes in gait signatures across a wide range of speeds, from very slow (0.3 m/s) to exceptionally fast (above the walk-to-run transition speed) in 17 able-bodied young adults. We further assessed whether 3D kinematic and/or kinetic (ground reaction forces, joint moments, and powers) data would improve the discrimination of gait signatures. Our study showed that gait signatures remained individual-specific across walking speeds: Notably, 3D kinematic signatures achieved exceptional accuracy (99.8%, confidence interval (CI) 99.1–100%) in classifying individuals, surpassing both 2D kinematics and 3D kinetics. Moreover, participants exhibited consistent, predictable linear changes in their gait signatures across the entire speed range. These changes were associated with participants’ preferred walking speeds, balance ability, cadence, and step length. These findings support gait signatures as a tool to characterize individual differences in gait and predict speed-induced changes in gait dynamics.

Abstract Physical human–robot interactions (pHRI) often provide mechanical force and power to aid walking without requiring voluntary effort from the human. Alternatively, principles of physical human–human interactions (pHHI) can inspire pHRI that aids walking by engaging human sensorimotor processes. We hypothesize that low-force pHHI can intuitively induce a person to alter their walking through haptic communication. In our experiment, an expert partner dancer influenced novice participants to alter step frequency solely through hand interactions. Without prior instruction, training, or knowledge of the expert’s goal, novices decreased step frequency 29% and increased step frequency 18% based on low forces (

Abstract Computational models can be critical to linking complex properties of muscle spindle organs to the sensory information that they encode during behaviours such as postural sway and locomotion where few muscle spindle recordings exist. Here, we augment a biophysical muscle spindle model to predict the muscle spindle sensory signal. Muscle spindles comprise several intrafusal muscle fibres with varied myosin expression and are innervated by sensory neurons that fire during muscle stretch. We demonstrate how cross‐bridge dynamics from thick and thin filament interactions affect the sensory receptor potential at the spike initiating region. Equivalent to the Ia afferent's instantaneous firing rate, the receptor potential is modelled as a linear sum of the force and rate change of force (yank) of a dynamic bag1 fibre and the force of a static bag2/chain fibre. We show the importance of inter‐filament interactions in (i) generating large changes in force at stretch onset that drive initial bursts and (ii) faster recovery of bag fibre force and receptor potential following a shortening. We show how myosin attachment and detachment rates qualitatively alter the receptor potential. Finally, we show the effect of faster recovery of receptor potential on cyclic stretch–shorten cycles. Specifically, the model predicts history‐dependence in muscle spindle receptor potentials as a function of inter‐stretch interval (ISI), pre‐stretch amplitude and the amplitude of sinusoidal stretches. This model provides a computational platform for predicting muscle spindle response in behaviourally relevant stretches and can link myosin expression seen in healthy and diseased intrafusal muscle fibres to muscle spindle function.

Abstract Muscle spindles relay vital mechanosensory information for movement and posture, but muscle spindle feedback is coupled to skeletal motion by a compliant tendon. Little is known about the effects of tendon compliance on muscle spindle feedback during movement, and the complex firing of muscle spindles makes these effects difficult to predict. Our goal was to investigate changes in muscle spindle firing using added series elastic elements (SEEs) to mimic a more compliant tendon, and to characterize the accompanying changes in firing with respect to muscle–tendon unit (MTU) and muscle fascicle displacements (recorded via sonomicrometry). Sinusoidal, ramp‐and‐hold and triangular stretches were analysed to examine potential changes in muscle spindle instantaneous firing rates (IFRs) in locomotor‐ and perturbation‐like stretches as well as serial history dependence. Added SEEs effectively reduced overall MTU stiffness and generally reduced muscle spindle firing rates, but the effect differed across stretch types. During sinusoidal stretches, peak and mean firing rates were not reduced and IFR was best‐correlated with fascicle velocity. During ramp stretches, SEEs reduced the initial burst, dynamic and static responses of the spindle. Notably, IFR was negatively related to fascicle displacement during the hold phase. During triangular stretches, SEEs reduced the mean IFR during the first and second stretches, affecting the serial history dependence of mean IFR. Overall, these results demonstrate that tendon compliance may attenuate muscle spindle feedback during movement, but these changes cannot be fully explained by reduced muscle fascicle length or velocity, or MTU force.

Joint hyper-resistance is a common symptom in neurological disorders. It has both neural and non-neural origins, but it has been challenging to distinguish different origins based on clinical tests alone. Combining instrumented tests with parameter identification based on a neuromechanical model may allow us to dissociate the different origins of joint hyper-resistance in individual patients. However, this requires that the model captures the underlying mechanisms. Here, we propose a neuromechanical model that, in contrast to previously proposed models, accounts for muscle short-range stiffness (SRS) and its interaction with muscle tone and reflex activity. We collected knee angle trajectories during the pendulum test in 15 children with cerebral palsy (CP) and 5 typically developing children. We did the test in two conditions – hold and pre-movement – that have been shown to alter knee movement. We modeled the lower leg as an inverted pendulum actuated by two antagonistic Hill-type muscles extended with SRS. Reflex activity was modeled as delayed, linear feedback from muscle force. We estimated neural and non-neural parameters by optimizing the fit between simulated and measured knee angle trajectories during the hold condition. The model could fit a wide range of knee angle trajectories in the hold condition. The model with personalized parameters predicted the effect of pre-movement demonstrating that the model captured the underlying mechanism and subject-specific deficits. Our model may help with the identification of neural and non-neural origins of joint hyper-resistance and thereby opens perspectives for improved diagnosis and treatment selection in children with spastic CP, but such applications require further studies to establish the method’s reliability.

Balance impairments are common in cerebral palsy. When balance is perturbed by backward support surface translations, children with cerebral palsy have increased co-activation of the plantar flexors and tibialis anterior muscle as compared to typically developing children. However, it is unclear whether increased muscle co-activation is a compensation strategy to improve balance control or is a consequence of reduced reciprocal inhibition. During translational perturbations, increased joint stiffness due to co-activation might aid balance control by resisting movement of the body with respect to the feet. In contrast, during rotational perturbations, increased joint stiffness will hinder balance control as it couples body to platform rotation. Therefore, we expect increased muscle co-activation in response to rotational perturbations if co-activation is caused by reduced reciprocal inhibition but not if it is merely a compensation strategy. We perturbed standing balance by combined backward translational and toe-up rotational perturbations in 20 children with cerebral palsy and 20 typically developing children. Perturbations induced forward followed by backward movement of the center of mass. We evaluated reactive muscle activity and the relation between center of mass movement and reactive muscle activity using a linear feedback model based on center of mass kinematics. In typically developing children, perturbations induced plantar flexor balance correcting muscle activity followed by tibialis anterior balance correcting muscle activity, which was driven by center of mass movement. In children with cerebral palsy, the switch from plantar flexor to tibialis anterior activity was less pronounced than in typically developing children due to increased muscle co-activation of the plantar flexors and tibialis anterior throughout the response. Our results thus suggest that a reduction in reciprocal inhibition causes muscle co-activation in reactive standing balance in children with cerebral palsy.

Objective: To evaluate the ability of a neural network to identify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using point-of-care electrocardiography obtained with a portable device. Patient and Methods: We enrolled 2827 patients in a prospective observational study, from December 10, 2020, through June 4, 2021, to determine the accuracy of a point-of-care, handheld, smartphone-compatible, artificial intelligence–enabled electrocardiography (ECG) (POC AI-ECG) in detecting asymptomatic SARS-CoV-2 infection using a modified version of an existing deep learning model framework trained on 12-lead ECG data. Results: Study participants were 48% (n=1067) female, 79% (n=1749) White, and 7% (n=153) endorsed previous COVID-19 infection. We found the POC AI-ECG algorithm was ineffective for detecting asymptomatic SARS-CoV-2 infection (area under curve, 0.56; 95% CI, 0.46-0.66), failing to adequately discriminate between ECGs performed among participants who tested positive compared to those who tested negative. Conclusion: Contrary to the prior 12-lead ECG study, a POC AI-ECG failed to reliably identify asymptomatic SARS-CoV-2 infection among adults. This study underscores the importance of prospective testing, assuring similar populations, and using similar signals or data when developing AI-ECG tools. Trial registration: clinicaltrials.gov Identifier: NCT04725097

Locomotion results from the interactions of highly nonlinear neural and biomechanical dynamics. Accordingly, understanding gait dynamics across behavioral conditions and individuals based on detailed modeling of the underlying neuromechanical system has proven difficult. Here, we develop a data-driven and generative modeling approach that recapitulates the dynamical features of gait behaviors to enable more holistic and interpretable characterizations and comparisons of gait dynamics. Specifically, gait dynamics of multiple individuals are predicted by a dynamical model that defines a common, low-dimensional, latent space to compare group and individual differences. We find that highly individualized dynamics-i.e., gait signatures-for healthy older adults and stroke survivors during treadmill walking are conserved across gait speed. Gait signatures further reveal individual differences in gait dynamics, even in individuals with similar functional deficits. Moreover, components of gait signatures can be biomechanically interpreted and manipulated to reveal their relationships to observed spatiotemporal joint coordination patterns. Lastly, the gait dynamics model can predict the time evolution of joint coordination based on an initial static posture. Our gait signatures framework thus provides a generalizable, holistic method for characterizing and predicting cyclic, dynamical motor behavior that may generalize across species, pathologies, and gait perturbations.

Objective: To develop a simple, interpretable value metric (VM) to assess the value of care of hospitals for specific procedures or conditions by operationalizing the value equation: Value = Quality/Cost. Patients and Methods: The present study was conducted on a retrospective cohort from 2015 to 2018 drawn from the 100% US sample of Medicare inpatient claims. The final cohort comprised 637,341 consecutive inpatient encounters with a cancer-related Medicare Severity-Diagnosis Related Grouping and 13,307 consecutive inpatient encounters with the International Classification of Diseases, Ninth Revision or International Classification of Diseases, Tenth Revision procedure code for partial or total gastrectomy. Claims-based demographic and clinical variables were used for risk adjustment, including age, sex, year, dual eligibility, reason for Medicare entitlement, and binary indicators for each of the Elixhauser comorbidities used in the Elixhauser mortality index. Risk-adjusted 30-day mortality and risk-adjusted encounter-specific costs were combined to form the VM, which was calculated as follows: number needed to treat = 1/(Mortalitynational − Mortalityhospital), and VM = number needed to treat × risk-adjusted cost per encounter. Results: Among hospitals with better-than-average 30-day cancer mortality rates, the cost to prevent 1 excess 30-day mortality for an inpatient cancer encounter ranged from $71,000 (best value) to $1.4 billion (worst value), with a median value of $543,000. Among hospitals with better-than-average 30-day gastrectomy mortality rates, the cost to prevent 1 excess 30-day mortality for an inpatient gastrectomy encounter ranged from $710,000 (best value) to $95 million (worst value), with a median value of $1.8 million. Conclusion: This simple VM may have utility for interpretable reporting of hospitals’ value of care for specific conditions or procedures. We found substantial inter- and intrahospital variation in value when defined as the costs of preventing 1 excess cancer or gastrectomy mortality compared with the national average, implying that hospitals with similar quality of care may differ widely in the value of that care.

Objective: To estimate rates and identify factors associated with asymptomatic COVID-19 in the population of Olmsted County during the prevaccination era. Patients and Methods: We screened first responders (n=191) and Olmsted County employees (n=564) for antibodies to SARS-CoV-2 from November 1, 2020 to February 28, 2021 to estimate seroprevalence and asymptomatic infection. Second, we retrieved all polymerase chain reaction (PCR)-confirmed COVID-19 diagnoses in Olmsted County from March 2020 through January 2021, abstracted symptom information, estimated rates of asymptomatic infection and examined related factors. Results: Twenty (10.5%; 95% CI, 6.9%-15.6%) first responders and 38 (6.7%; 95% CI, 5.0%-9.1%) county employees had positive antibodies; an additional 5 (2.6%) and 10 (1.8%) had prior positive PCR tests per self-report or medical record, but no antibodies detected. Of persons with symptom information, 4 of 20 (20%; 95% CI, 3.0%-37.0%) first responders and 10 of 39 (26%; 95% CI, 12.6%-40.0%) county employees were asymptomatic. Of 6020 positive PCR tests in Olmsted County with symptom information between March 1, 2020, and January 31, 2021, 6% (n=385; 95% CI, 5.8%-7.1%) were asymptomatic. Factors associated with asymptomatic disease included age (0-18 years [odds ratio {OR}, 2.3; 95% CI, 1.7-3.1] and >65 years [OR, 1.40; 95% CI, 1.0-2.0] compared with ages 19-44 years), body mass index (overweight [OR, 0.58; 95% CI, 0.44-0.77] or obese [OR, 0.48; 95% CI, 0.57-0.62] compared with normal or underweight) and tests after November 20, 2020 ([OR, 1.35; 95% CI, 1.13-1.71] compared with prior dates). Conclusion: Asymptomatic rates in Olmsted County before COVID-19 vaccine rollout ranged from 6% to 25%, and younger age, normal weight, and later tests dates were associated with asymptomatic infection.

Summary: There is a wealth of software that utilizes single-cell RNA-seq (scRNA-seq) data to deconvolve spatial transcriptomic spots, which currently are not yet at single-cell resolution. Here we provide protocols for implementing Seurat and Giotto packages to elucidate cell-type distribution in our example human ureter scRNA-seq dataset. We also describe how to create a stand-alone interactive web application using Seurat libraries to visualize and share our results.For complete details on the use and execution of this protocol, please refer to Fink et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Purpose of Review: Magnesium is an essential mineral for bone metabolism, but little is known about how magnesium intake alters fracture risk. We conducted a narrative review to better understand how magnesium intake, through supplementation, diet, or altering the concentration of dialysate magnesium, affects mineral bone disease and the risk of fracture in individuals across the spectrum of kidney disease. Sources of Information: Peer-reviewed clinical trials and observational studies. Methods: We searched for relevant articles in MEDLINE and EMBASE databases. The methodologic quality of clinical trials was assessed using a modified version of the Downs and Black criteria checklist. Key Findings: The role of magnesium intake in fracture prevention is unclear in both the general population and in patients receiving maintenance dialysis. In those with normal kidney function, 2 meta-analyses showed higher bone mineral density in those with higher dietary magnesium, whereas 1 systematic review showed no effect on fracture risk. In patients receiving maintenance hemodialysis or peritoneal dialysis, a higher concentration of dialysate magnesium is associated with a lower concentration of parathyroid hormone, but little is known about other bone-related outcomes. In 2 observational studies of patients receiving hemodialysis, a higher concentration of serum magnesium was associated with a lower risk of hip fracture. Limitations: This narrative review included only articles written in English. Observed effects of magnesium intake in the general population may not be applicable to those with chronic kidney disease particularly in those receiving dialysis.

Summary: Characterizing the cellular heterogeneity of human ureter tissues using single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics provides a detailed atlas of cell types, signaling networks, and potential cell-cell cross talk underlying developmental and regenerative pathways. We describe an optimized protocol for generating, cryopreserving, and thawing single-cell suspensions from ureter tissues isolated post-cystectomy for scRNA-seq. In addition, we describe an optimized protocol for cryopreserving human ureter tissues for 10x Genomics Visium spatial gene expression platform.For complete details on the use and execution of this protocol, please refer to Fink et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Optimal control simulations have shown that both musculoskeletal dynamics and physiological noise are important determinants of movement. However, due to the limited efficiency of available computational tools, deterministic simulations of movement focus on accurately modelling the musculoskeletal system while neglecting physiological noise, and stochastic simulations account for noise while simplifying the dynamics. We took advantage of recent approaches where stochastic optimal control problems are approximated using deterministic optimal control problems, which can be solved efficiently using direct collocation. We were thus able to extend predictions of stochastic optimal control as a theory of motor coordination to include muscle coordination and movement patterns emerging from non-linear musculoskeletal dynamics. In stochastic optimal control simulations of human standing balance, we demonstrated that the inclusion of muscle dynamics can predict muscle co-contraction as minimal effort strategy that complements sensorimotor feedback control in the presence of sensory noise. In simulations of reaching, we demonstrated that nonlinear multi-segment musculoskeletal dynamics enables complex perturbed and unperturbed reach trajectories under a variety of task conditions to be predicted. In both behaviors, we demonstrated how interactions between task constraint, sensory noise, and the intrinsic properties of muscle influence optimal muscle coordination patterns, including muscle co-contraction, and the resulting movement trajectories. Our approach enables a true minimum effort solution to be identified as task constraints, such as movement accuracy, can be explicitly imposed, rather than being approximated using penalty terms in the cost function. Our approximate stochastic optimal control framework predicts complex features, not captured by previous simulation approaches, providing a generalizable and valuable tool to study how musculoskeletal dynamics and physiological noise may alter neural control of movement in both healthy and pathological movements.

Abstract Background A substantial number of clinical studies have demonstrated the functional recovery induced by the use of brain-computer interface (BCI) technology in patients after stroke. The objective of this review is to evaluate the effect sizes of clinical studies investigating the use of BCIs in restoring upper extremity function after stroke and the potentiating effect of transcranial direct current stimulation (tDCS) on BCI training for motor recovery. Methods The databases (PubMed, Medline, EMBASE, CINAHL, CENTRAL, PsycINFO, and PEDro) were systematically searched for eligible single-group or clinical controlled studies regarding the effects of BCIs in hemiparetic upper extremity recovery after stroke. Single-group studies were qualitatively described, but only controlled-trial studies were included in the meta-analysis. The PEDro scale was used to assess the methodological quality of the controlled studies. A meta-analysis of upper extremity function was performed by pooling the standardized mean difference (SMD). Subgroup meta-analyses regarding the use of external devices in combination with the application of BCIs were also carried out. We summarized the neural mechanism of the use of BCIs on stroke. Results A total of 1015 records were screened. Eighteen single-group studies and 15 controlled studies were included. The studies showed that BCIs seem to be safe for patients with stroke. The single-group studies consistently showed a trend that suggested BCIs were effective in improving upper extremity function. The meta-analysis (of 12 studies) showed a medium effect size favoring BCIs for improving upper extremity function after intervention (SMD = 0.42; 95% CI = 0.18–0.66; I 2 = 48%; P

The mechanisms underlying associations between cognitive set shifting impairments and balance dysfunction are unclear. Cognitive set shifting refers to the ability to flexibly adjust behavior to changes in task rules or contexts, which could be involved in flexibly adjusting balance recovery behavior to different contexts, such as the direction the body is falling. Prior studies found associations between cognitive set shifting impairments and severe balance dysfunction in populations experiencing frequent falls. The objective of this study was to test whether cognitive set shifting ability is expressed in successful balance recovery behavior in older adults with high clinical balance ability (N = 19, 71 ± 7 years, 6 female). We measured cognitive set shifting ability using the Trail Making Test and clinical balance ability using the miniBESTest. For most participants, cognitive set shifting performance (Trail Making Test B-A = 37 ± 20 s) was faster than normative averages (46 s for comparable age and education levels), and balance ability scores (miniBESTest = 25 ± 2/28) were above the threshold for fall risk (23 for people between 70 and 80 years). Reactive balance recovery in response to support-surface translations in anterior and posterior directions was assessed in terms of body motion, muscle activity, and brain activity. Across participants, lower cognitive set shifting ability was associated with smaller peak center of mass displacement during balance recovery, lower directional specificity of late phase balance-correcting muscle activity (i.e., greater antagonist muscle activity 200–300 ms after perturbation onset), and larger cortical N1 responses (100–200 ms). None of these measures were associated with clinical balance ability. Our results suggest that cognitive set shifting ability is expressed in balance recovery behavior even in the absence of profound clinical balance disability. Specifically, our results suggest that lower flexibility in cognitive task performance is associated with lower ability to incorporate the directional context into the cortically mediated later phase of the motor response. The resulting antagonist activity and stiffer balance behavior may help explain associations between cognitive set shifting impairments and frequent falls.

Principles from human-human physical interaction may be necessary to design more intuitive and seamless robotic devices to aid human movement. Previous studies have shown that light touch can aid balance and that haptic communication can improve performance of physical tasks, but the effects of touch between two humans on walking balance has not been previously characterized. This study examines physical interaction between two persons when one person aids another in performing a beam-walking task. 12 pairs of healthy young adults held a force sensor with one hand while one person walked on a narrow balance beam (2 cm wide x 3.7 m long) and the other person walked overground by their side. We compare balance performance during partnered vs. solo beam-walking to examine the effects of haptic interaction, and we compare hand interaction mechanics during partnered beam-walking vs. overground walking to examine how the interaction aided balance. While holding the hand of a partner, participants were able to walk further on the beam without falling, reduce lateral sway, and decrease angular momentum in the frontal plane. We measured small hand force magnitudes (mean of 2.2 N laterally and 3.4 N vertically) that created opposing torque components about the beam axis and calculated the interaction torque, the overlapping opposing torque that does not contribute to motion of the beam-walker’s body. We found higher interaction torque magnitudes during partnered beam-walking vs. partnered overground walking, and correlation between interaction torque magnitude and reductions in lateral sway. To gain insight into feasible controller designs to emulate human-human physical interactions for aiding walking balance, we modeled the relationship between each torque component and motion of the beam-walker’s body as a mass-spring-damper system. Our model results show opposite types of mechanical elements (active vs. passive) for the two torque components. Our results demonstrate that hand interactions aid balance during partnered beam-walking by creating opposing torques that primarily serve haptic communication, and our model of the torques suggest control parameters for implementing human-human balance aid in human-robot interactions.

We investigated the effects of mirror visual feedback (MVF), with reference to using a glass wall or a covered mirror, on the reduction of spatial neglect for patients with stroke. A total of 21 subacute patients with left spatial neglect after right-hemispheric stroke were randomly assigned to 3 groups: MVF, sham 1 (viewing the hemiparetic arm through the transparent glass during bilateral arm movement) and sham 2 (using a covered mirror). The 3-week treatment program for all groups consisted of 12 sessions of movement tasks for the hemiparetic arm graded according to the severity of arm impairments. Blinded assessments were administered at pre/post and a three-week follow-up. The results showed that there was no significant advantage for MVF than sham 1; however, MVF was more beneficial than sham 2, as shown by the line crossing (p = 0.022). Improvement in discriminating the left-gap figures on the left and right side of the page in the Gap Detection Test was greater in MVF than using the covered mirror (p = 0.013; p = 0.010), showing a slight advantage of MVF in alleviating allocentric symptoms. Our study confirms that MVF was superior to using a covered mirror as a method for reducing spatial neglect and in alleviating its allocentric symptoms, but no significant advantage over bilateral arm movement through transparent glass was found. Further research in comparing their therapeutic effects is warranted.

Background Organism susceptibilities for trauma-associated pneumonia (TAP) differ from those in other patient populations, including the critically ill. The purpose of this study was to identify common organisms and their susceptibilities in the respiratory isolates of trauma patients diagnosed with pneumonia within the first 7 days of hospital admission, and to create a TAP-specific disease-state antibiogram to guide empiric antibiotic therapy in this patient population.Methods This study was a retrospective review of adult trauma patients with pneumonia admitted between September 1, 2015 and August 31, 2018. Patients included were diagnosed with and treated for pneumonia, with respiratory cultures drawn within the first 7 hospital-days; both culture-positive and culture-negative patients were included. Subgroup antibiograms were made for diagnosis made on days 1–3, 4–5, and 6–7.Results There were 131 patients included with a median age of 45; 85% were male, and 31% were illicit drug users. Most patients (63%) had ventilator-associated pneumonia, and most respiratory samples (77%) were obtained via bronchoalveolar lavage. Cultures were positive in 109 patients and negative in 22. There were 144 total isolates; 54% were Gram-negative bacteria. The most common Gram-negative pathogens were Haemophilus influenzae (16%) and Klebsiella pneumoniae (15%). The most common Gram-positive pathogen was Staphylococcus aureus; methicillin-resistant S. aureus (MRSA) constituted 8% of all isolates. With culture-negative patients counted as susceptible, ceftriaxone monotherapy and ceftriaxone+vancomycin susceptibilities were 85% and 94%, respectively. Susceptibilities to cefazolin, ampicillin/sulbactam, cefepime, piperacillin/tazobactam, and levofloxacin were 49%, 69%, 91%, 90%, and 92%, respectively. Illicit drug use and day of pneumonia diagnosis did not appreciably affect antibiotic susceptibilities.Conclusions For TAP diagnosed within the first 7 days of hospital admission, ceftriaxone monotherapy is adequate as empiric therapy, including in ventilated patients. The addition of vancomycin can be considered in patients with MRSA risk factors or who are critically ill.Level of evidence Level III, prognostic and epidemiological.

Heightened reliance on the cerebral cortex for postural stability with aging is well-known, yet the cortical mechanisms for balance control, particularly in relation to balance function, remain unclear. Here we aimed to investigate motor cortical activity in relation to the level of balance challenge presented during reactive balance recovery and identify circuit-specific interactions between motor cortex and prefrontal or somatosensory regions in relation to metrics of balance function that predict fall risk. Using electroencephalography, we assessed motor cortical beta power, and beta coherence during balance reactions to perturbations in older adults. We found that individuals with greater motor cortical beta power evoked following standing balance perturbations demonstrated lower general clinical balance function. Individual older adults demonstrated a wide range of cortical responses during balance reactions at the same perturbation magnitude, showing no group-level change in prefrontal- or somatosensory-motor coherence in response to perturbations. However, older adults with the highest prefrontal-motor coherence during the post-perturbation, but not pre-perturbation, period showed greater cognitive dual-task interference (DTI) and elicited stepping reactions at lower perturbation magnitudes. Our results support motor cortical beta activity as a potential biomarker for individual level of balance challenge and implicate prefrontal-motor cortical networks in distinct aspects of balance control involving response inhibition of reactive stepping in older adults. Cortical network activity during balance may provide a neural target for precision-medicine efforts aimed at fall prevention with aging.

Event-related desynchronization (ERD), as a proxy for mirror neuron activity, has been used as a neurophysiological marker for motor execution after mirror visual feedback (MVF). Using EEG, this study investigated ERD upon the immediate effects of single-session MVF in unimanual arm movements compared with the ERD effects occurring without a mirror, in two groups: stroke patients with left hemiplegia and their healthy counterparts. During EEG recordings, each group performed one session of mirror therapy training in three task conditions: with a mirror, with no mirror, and with a covered mirror. An asymmetry index was calculated from the subtraction of the event-related spectrum perturbations between the C3 and C4 electrodes located over the sensorimotor cortices contralateral and ipsilateral to the moved arm. Results of the effect of task versus group in contralateral and ipsilateral motor areas showed that there was a significant effect of task condition at the contralateral motor area in the high beta band (17–35 Hz) at C3. High beta ERD showed that the suppression was greater over the contralateral hemisphere than it was over the ipsilateral hemisphere in both study groups. The magnitude of low beta (12–16 Hz) ERD in patients with stroke was more suppressed in contralesional C3 under the no mirror compared to that of the covered mirror and similarly more suppressed in ipsilesional C4 ERD under the no mirror compared to that of the mirror condition. The correlation analysis revealed that the magnitude of ERSP power correlated significantly with arm severity in the low and high beta bands in patients with stroke, and a higher asymmetry index in the low beta band was associated with higher arm functioning under the no-mirror condition. There was a shift in sensorimotor ERD toward the contralateral hemisphere as induced by MVF accompanying unimanual movement in both stroke patients and healthy controls. The use of ERD in the low beta band as a neurophysiological marker to indicate the relationships between the amount of MVF-induced ERD attenuation and motor severity, and the outcome indicator for improving stroke patients’ neuroplasticity in clinical trials using MVF are warranted to be explored in the future.

Objective: This study assesses the attitudes and preferences of Chinese clinicians toward their involvement in shared decision making (SDM). Methods: From May 2014 to May 2015, 200 Chinese clinicians from two hospitals were enrolled to complete a survey on their attitude towards SDM. We conducted the survey via face-to-face interviews before and after an educational intervention on SDM among young Chinese clinicians. The clinicians were asked to give the extent of agreement to SDM. They also gave the extent of difficulty in using decision aids (DAs) during the SDM process. The variation in the range of responses to each question before and after the SDM intervention was recorded. The frequency of changed responses was analyzed by using JMP 6.0 software. Data were statistically analyzed using Chi-square and Mann–Whitney U tests, as appropriate to the data type. Multiple logistic regressions were used to test for those factors significantly and independently associated with preference for an approach for each scenario. Results: Of the 200 young Chinese clinicians sampled, 59.0% indicated a preference for SDM and a desire to participate in SDM before receiving education or seeing the DA, and this number increased to 69.0% after seeing the DA with the sample video of the SDM process on Statin Choice. However, 28.5% of the respondents still reported that, in their current practice, they make clinical decisions on behalf of their patients. The clinicians who denied a desire to use the DA stated that the main barriers to implement SDM or DA use in China are lack of time and knowledge of SDM. Conclusions: Most young Chinese clinicians want to participate in SDM. However, they state the main barriers to perform SDM are lack of experience and time. The educational intervention about SDM that exposes clinicians to DAs was found to increase their receptivity. Keywords: Decision aid, Shared-decision making, Cardiovascular risk, China

Abstract Background Guidelines recommend shared decision making (SDM) for determining whether to use statins to prevent cardiovascular events in at-risk patients. We sought to develop a toolkit to facilitate the cross-organizational spread and scale of a SDM intervention called the Statin Choice Conversation Aid (SCCA) by (i) assessing the work stakeholders must do to implement the tool; and (ii) orienting the resulting toolkit’s components to communicate and mitigate this work. Methods We conducted multi-level and mixed methods (survey, interview, observation, focus group) characterizations of the contexts of 3 health systems (n = 86, 84, and 26 primary care clinicians) as they pertained to the impending implementation of the SCCA. We merged the data within implementation outcome domains of feasibility, appropriateness, and acceptability. Using Normalization Process Theory, we then characterized and categorized the work stakeholders did to implement the tool. We used clinician surveys and IP address-based tracking to calculate SCCA usage over time and judged how stakeholder effort was allocated to influence outcomes at 6 and 18 months. After assessing the types and impact of the work, we developed a multi-component toolkit. Results At baseline, the three contexts differed regarding feasibility, acceptability, and appropriateness of implementation. The work of adopting the tool was allocated across many strategies in complex and interdependent ways to optimize these domains. The two systems that allocated the work strategically had higher uptake (5.2 and 2.9 vs. 1.1 uses per clinician per month at 6 months; 3.8 and 2.1 vs. 0.4 at 18 months, respectively) than the system that did not. The resulting toolkit included context self-assessments intended to guide stakeholders in considering the early work of SCCA implementation; and webinars, EMR integration guides, video demonstrations, and an implementation team manual aimed at supporting this work. Conclusions We developed a multi-component toolkit for facilitating the scale-up and spread of a tool to promote SDM across clinical settings. The theory-based approach we employed aimed to distinguish systems primed for adoption and support the work they must do to achieve implementation. Our approach may have value in orienting the development of multi-component toolkits and other strategies aimed at facilitating the efficient scale up of interventions. Trial registration ClinicalTrials.gov NCT02375815.

Platelet aggregates generate contractile forces that contribute to their cohesion and adhesion. Here, Ting et al. develop a microfluidic device to measure contractile forces generated by platelet aggregates, and find it can detect the response of platelets to pharmacological agents and predict bleeding risk in trauma patients.

IntroductionPatients' burden from lung cancer treatment is not well researched, but this understanding can facilitate a patient-centred treatment approach. Current models of treatment burden suggest it is influenced by a patient's perception of their disease and treatment and their capacity to do the work required to treat their disease.MethodsSixteen patients and 1 carer who were undergoing or had completed conventional or stereotactic ablative radiotherapy, chemotherapy or immunotherapy for lung cancer in the last 6 months participated in a semi-structured interview. A treatment burden framework was used with three main themes: a) treatment work, b) consequences of treatment and c) psychosocial factors affecting treatment burden.ResultsThe majority of patients did not feel unduly burdened by treatment tasks, despite having a large treatment-associated workload. Many saw treatment as a priority, causing them to restructure their life to accommodate for it. Patients wished that they would have been better informed about the lifestyle changes that they would have to make before treatment for lung cancer commenced and that the health service would provide services to assist them with this task.DiscussionWhile there was a large burden associated with lung cancer treatment, patients felt motivated and equipped to manage the workload because the disease was considered severe and life-threatening, and the treatment was seen as beneficial. Before initiating treatment for lung cancer, patients should be informed about lifestyle changes they likely have to make and should be offered assistance.

BackgroundLittle is known about the treatment burden experienced by patients with obstructive sleep apnoea (OSA) who use continuous positive airway pressure (CPAP) therapy.Participants18 patients (33.3% males, mean age 59.7±11.8 years) with OSA who use CPAP therapy were interviewed.MethodsPatients treated with CPAP for OSA at a tertiary hospital outpatient clinic in Sydney, Australia, were invited to participate in an interview in person or via phone. Semi-structured interviews were used to explore the treatment burden associated with using CPAP. The interviews were recorded, transcribed, and analysed using NVivo 12 qualitative analysis software.ResultsFour categories of OSA-specific treatment burden were identified: healthcare tasks, consequences of healthcare tasks, exacerbating and alleviating factors of treatment burden. Participants reported a significant burden associated with using CPAP, independently of how frequently they used their device. Common sources of their treatment burden included attending healthcare appointments, the financial cost of treatment, lifestyle changes, treatment-related side effects and general discomfort.ConclusionsThis study demonstrated that there is a significant treatment burden associated with the use of CPAP, and that treatment non-adherence is not the only consequence of treatment burden. Other consequences include relationship burden, stigma and financial burden. It is important for physicians to identify other negative impacts of treatment burden in order to optimise the patient experience.

Although Parkinson disease (PD) causes profound balance impairments, we know very little about how PD impacts the sensorimotor networks we rely on for automatically maintaining balance control. In young healthy people and animals, muscles are activated in a precise temporal and spatial organization when the center of body mass (CoM) is unexpectedly moved that is largely automatic and determined by feedback of CoM motion. Here, we show that PD alters the sensitivity of the sensorimotor feedback transformation. Importantly, sensorimotor feedback transformations for balance in PD remain temporally precise, but become spatially diffuse by recruiting additional muscle activity in antagonist muscles during balance responses. The abnormal antagonist muscle activity remains precisely time-locked to sensorimotor feedback signals encoding undesirable motion of the body in space. Further, among people with PD, the sensitivity of abnormal antagonist muscle activity to CoM motion varies directly with the number of recent falls. Our work shows that in people with PD, sensorimotor feedback transformations for balance are intact but disinhibited in antagonist muscles, likely contributing to balance deficits and falls.

Leg rigidity is associated with frequent falls in people with Parkinson’s disease (PD), suggesting a potential role in functional balance and gait impairments. Changes in the neural state due to secondary tasks, e.g., activation maneuvers, can exacerbate (or “activate”) rigidity, possibly increasing the risk of falls. However, the subjective interpretation and coarse classification of the standard clinical rigidity scale has prohibited the systematic, objective assessment of resting and activated leg rigidity. The pendulum test is an objective diagnostic method that we hypothesized would be sensitive enough to characterize resting and activated leg rigidity. We recorded kinematic data and electromyographic signals from rectus femoris and biceps femoris during the pendulum test in 15 individuals with PD, spanning a range of leg rigidity severity. From the recorded data of leg swing kinematics, we measured biomechanical outcomes including first swing excursion, first extension peak, number and duration of the oscillations, resting angle, relaxation index, maximum and minimum angular velocity. We examined associations between biomechanical outcomes and clinical leg rigidity score. We evaluated the effect of increasing rigidity through activation maneuvers on biomechanical outcomes. Finally, we assessed whether either biomechanical outcomes or changes in outcomes with activation were associated with a fall history. Our results suggest that the biomechanical assessment of the pendulum test can objectively quantify parkinsonian leg rigidity. We found that the presence of high rigidity during clinical exam significantly impacted biomechanical outcomes, i.e., first extension peak, number of oscillations, relaxation index, and maximum angular velocity. No differences in the effect of activation maneuvers between groups with clinically assessed low rigidity were observed, suggesting that activated rigidity may be independent of resting rigidity and should be scored as independent variables. Moreover, we found that fall history was more common among people whose rigidity was increased with a secondary task, as measured by biomechanical outcomes. We conclude that different mechanisms contributing to resting and activated rigidity may play an important yet unexplored functional role in balance impairments. The pendulum test may contribute to a better understanding of fundamental mechanisms underlying motor symptoms in PD, evaluating the efficacy of treatments, and predicting the risk of falls.

Despite decades of research, we lack a mechanistic framework capable of predicting how movement-related signals are transformed into the diversity of muscle spindle afferent firing patterns observed experimentally, particularly in naturalistic behaviors. Here, a biophysical model demonstrates that well-known firing characteristics of mammalian muscle spindle Ia afferents – including movement history dependence, and nonlinear scaling with muscle stretch velocity – emerge from first principles of muscle contractile mechanics. Further, mechanical interactions of the muscle spindle with muscle-tendon dynamics reveal how motor commands to the muscle (alpha drive) versus muscle spindle (gamma drive) can cause highly variable and complex activity during active muscle contraction and muscle stretch that defy simple explanation. Depending on the neuromechanical conditions, the muscle spindle model output appears to ‘encode’ aspects of muscle force, yank, length, stiffness, velocity, and/or acceleration, providing an extendable, multiscale, biophysical framework for understanding and predicting proprioceptive sensory signals in health and disease.

This article aims to uncover novel insights into personality factors and consumer video game engagement modeling. This research empirically validates the role of specific HEXACO personality factors that foster consumer engagement (CE) in electronic sports (eSports) users. Using a survey-based approach, we incorporated the HEXACO 60 items and consumer video game engagement scales for data collection. Data were collected from eSports users, with 250 valid responses. WarpPLS 6.0 was used for partial least squares–structural equation modeling analyses comprising measurement and structural model assessment. The results showed that the reflective measurement model is reliable and sound, whereas the second-order formative measurement model also meets the criteria of indicator weights and collinearity values variance inflation factor (VIF). The results based on the structural model indicate that openness to experience, extraversion, agreeableness, and conscientiousness positively predict CE in eSports. This article is first among others that conceptualizes and validates the HEXACO personality traits as a reflective formative model using the hierarchical component model approach. The research model carries the explanatory capacity for CE in eSports concerning personality dimensions as indicated by the HEXACO model. It highlights the potential benefits of such research especially to marketers who could potentially employ personality modeling to develop tailored strategies to increase CE in video games.

The pendulum test assesses quadriceps spasticity by dropping the lower leg of a relaxed patient from the horizontal position and observing limb movement. The first swing excursion (FS) decreases with increasing spasticity severity. Our recent simulation study suggests that the reduced initial swing results from muscle short-range stiffness and its interaction with reflex hyper-excitability. Short-range stiffness emerges from the thixotropic behavior of muscles where fiber stiffness upon stretch increases when the muscle is held isometric. Fiber stiffness might thus be higher during the first swing of the pendulum test than during consecutive swings. In addition, it has recently been suggested that muscle spindle firing reflects fiber force rather than velocity and therefore, reflex activity might depend on fiber stiffness. If this hypothesized mechanism is true, we expect to observe larger first swing excursions and reduced reflex muscle activity when the leg is moved rather than kept isometric before release, especially in patients with increased reflex activity. We performed the pendulum test in 15 children with cerebral palsy (CP) and 15 age-matched typically developing (TD) children in two conditions. In the hold condition, the leg was kept isometric in the extended position before release. In the movement condition, the leg was moved up and down before release to reduce the contribution of short-range stiffness. Knee kinematics and muscle activity were recorded. Moving the leg before release increased first swing excursion (p < 0.001) and this increase was larger in children with CP (21°) than in TD children (8°) (p < 0.005). In addition, pre-movement delayed reflex onset by 87 ms (p < 0.05) and reduced reflex activity as assessed through the area under the curve of rectus femoris electromyography (p < 0.05) in children with CP. The movement history dependence of pendulum kinematics and reflex activity supports our hypothesis that muscle short-range stiffness and its interaction with reflex hyper-excitability contribute to joint hyper-resistance in spastic CP. Our results have implications for standardizing movement history in clinical tests of spasticity and for understanding the role of spasticity in functional movements, where movement history differs from movement history in clinical tests.

Abstract: Transcatheter aortic valve replacement is a relatively recent revolutionary treatment that has now become a standard procedure for treating severe aortic stenosis. In this article, the authors review the clinical history of transcatheter aortic valve replacement, summarize the major clinical trials, and describe the evolution of the technique over time. In doing so, the authors hope to provide a clear and concise review of the history and clinical evidence behind transcatheter aortic valve replacement.

BackgroundTreatment for tuberculosis lasts for a minimum of 6 months. The treatment burden experienced by patients in a low-incidence setting where directly observed therapy is the standard of care is not well-known.MethodsPatients receiving tuberculosis treatment through the chest clinic at a tertiary hospital in Sydney, Australia, participated in a semi-structured interview. The interviews explored the treatment burden experienced by patients and possible solutions to ameliorate this burden. Interviews were conducted until data saturation was achieved. They were recorded, transcribed and analysed using NVivo 12 software.ResultsTwenty participants (80% male, mean age 40 years) with pulmonary (n = 13) and extra-pulmonary (n = 7) tuberculosis were interviewed. Participants experienced healthcare, financial, social and medication burdens along with lifestyle changes due to treatment. Medication intake was challenging due to the high number of pills, and 55% (n = 11) of patients experienced fatigue amongst other side effects. Patients found clinic-based directly observed therapy inconvenient, especially those working and/or studying. Suggestions to lessen treatment burden included reducing medication burden and better access to health services.ConclusionTuberculosis treatment is associated with substantial treatment burden for patients. Measures to reduce treatment burden including alternative treatment delivery methods which are more accommodating to patients than clinic-based directly observed therapy, such as video directly observed therapy or partially self -administered treatment, should be considered on a case-by-case basis.

Stroke is a leading cause of long-term disability worldwide and often impairs walking ability. To improve recovery of walking function post-stroke, researchers have investigated the use of treatments such as fast functional electrical stimulation (FastFES). During FastFES treatments, individuals post-stroke walk on a treadmill at their fastest comfortable speed while electrical stimulation is delivered to two muscles of the paretic ankle, ideally to improve paretic leg propulsion and toe clearance. However, muscle selection and stimulation timing are currently standardized based on clinical intuition and a one-size-fits-all approach, which may explain in part why some patients respond to FastFES training while others do not. This study explores how personalized neuromusculoskeletal models could potentially be used to enable individual-specific selection of target muscles and stimulation timing to address unique functional limitations of individual patients post-stroke. Treadmill gait data, including EMG, surface marker positions, and ground reactions, were collected from an individual post-stroke who was a non-responder to FastFES treatment. The patient's gait data were used to personalize key aspects of a full-body neuromusculoskeletal walking model, including lower-body joint functional axes, lower-body muscle force generating properties, deformable foot-ground contact properties, and paretic and non-paretic leg neural control properties. The personalized model was utilized within a direct collocation optimal control framework to reproduce the patient's unstimulated treadmill gait data (verification problem) and to generate three stimulated walking predictions that sought to minimize inter-limb propulsive force asymmetry (prediction problems). The three predictions used: (1) Standard muscle selection (gastrocnemius and tibialis anterior) with standard stimulation timing, (2) Standard muscle selection with optimized stimulation timing, and (3) Optimized muscle selection (soleus and semimembranosus) with optimized stimulation timing. Relative to unstimulated walking, the optimal control problems predicted a 41% reduction in propulsive force asymmetry for scenario (1), a 45% reduction for scenario (2), and a 64% reduction for scenario (3), suggesting that non-standard muscle selection may be superior for this patient. Despite these predicted improvements, kinematic symmetry was not noticeably improved for any of the walking predictions. These results suggest that personalized neuromusculoskeletal models may be able to predict personalized FastFES training prescriptions that could improve propulsive force symmetry, though inclusion of kinematic requirements would be necessary to improve kinematic symmetry as well.

We lack reliable methods to continuously assess localized, resting-state muscle activity that are comparable across individuals. Near-infrared spectroscopy (NIRS) provides a low-cost, non-invasive means to assess localized, resting-state muscle oxygen metabolism during venous or arterial occlusions (VO2VO and VO2AO, respectively). However, this technique is not suitable for continuous monitoring, and its utility is limited to those who can tolerate occlusions. Combining NIRS with diffuse correlated spectroscopy (DCS) enables continuous measurement of an index of muscle oxygen metabolism (VO2i). Despite the lack of previous validation, VO2i is employed as a measure of oxygen metabolism in the muscle. Here we characterized measurement repeatability and compared VO2i with VO2VO and VO2AO in the medial gastrocnemius (MG) in 9 healthy adults. Intra-participant repeatability of VO2i, VO2VO, and VO2AO were excellent. VO2i was not significantly correlated with VO2AO (p = 0.15) nor VO2VO (p = 0.55). This lack of correlation suggests that the variability in the calibration coefficient between VO2i and VO2AO/VO2VO in the MG is substantial across participants. Thus, it is preferable to calibrate VO2i prior to every monitoring session. Important future work is needed to compare VO2i against gold standard modalities such as positron emission tomography or magnetic resonance imaging.

BACKGROUND:Abnormal antagonist leg muscle activity could indicate increased muscle co-contraction and clarify mechanisms of balance impairments in Parkinson's disease (PD). Prior studies in carefully selected patients showed PD patients demonstrate earlier, longer, and larger antagonist muscle activation during reactive balance responses to perturbations. RESEARCH QUESTION:Here, we tested whether antagonist leg muscle activity was abnormal in a group of PD patients who were not selected for phenotype and most of whom had volunteered for exercise-based rehabilitation. METHODS:We compared antagonist activation during reactive balance responses to multidirectional support-surface translation perturbations in 31 patients with mild-moderate PD (age 68±9; H&Y 1-3; UPDRS-III 32±10) and 13 matched individuals (age 65±9). We quantified modulation of muscle activity (i.e., the ability to activate and inhibit muscles appropriately according to the perturbation direction) using modulation indices (MI) derived from minimum and maximum EMG activation levels observed across perturbation directions. RESULTS:Antagonist leg muscle activity was abnormal in unselected PD patients compared to controls. Linear mixed models identified significant associations between impaired modulation and PD (P

The robustness of motor outputs to muscle dysfunction has been investigated using musculoskeletal modeling, but with conflicting results owing to differences in model complexity and motor tasks. Our objective was to systematically study how the number of kinematic degrees of freedom, and the number of independent muscle actuators alter the robustness of motor output to muscle dysfunction. We took a detailed musculoskeletal model of the human leg and systematically varied the model complexity to create six models with either 3 or 7 kinematic degrees of freedom and either 14, 26, or 43 muscle actuators. We tested the redundancy of each model by quantifying the reduction in sagittal plane feasible force set area when a single muscle was removed. The robustness of feasible force set area to the loss of any single muscle, i.e. general single muscle loss increased with the number of independent muscles and decreased with the number of kinematic degrees of freedom, with the robust area varying from 1% and 52% of the intact feasible force set area. The maximum sensitivity of the feasible force set to the loss of any single muscle varied from 75% to 26% of the intact feasible force set area as the number of muscles increased. Additionally, the ranges of feasible muscle activation for maximum force production were largely unconstrained in many cases, indicating ample musculoskeletal redundancy even for maximal forces. We propose that ratio of muscles to kinematic degrees of freedom can be used as a rule of thumb for estimating musculoskeletal redundancy in both simulated and real biomechanical systems.

Background: Previous studies have demonstrated that post-stroke gait rehabilitation combining functional electrical stimulation (FES) applied to the ankle muscles during fast treadmill walking (FastFES) improves gait biomechanics and clinical walking function. However, there is considerable inter-individual variability in response to FastFES. Although FastFES aims to sculpt ankle muscle coordination, whether changes in ankle muscle activity underlie observed gait improvements is unknown. The aim of this study was to investigate three cases illustrating how FastFES modulates ankle muscle recruitment during walking.Methods: We conducted a preliminary case series study on three individuals (53–70 y; 2 M; 35–60 months post-stroke; 19–22 lower extremity Fugl-Meyer) who participated in 18 sessions of FastFES (3 sessions/week; ClinicalTrials.gov: NCT01668602). Clinical walking function (speed, 6-min walk test, and Timed-Up-and-Go test), gait biomechanics (paretic propulsion and ankle angle at initial-contact), and plantarflexor (soleus)/dorsiflexor (tibialis anterior) muscle recruitment were assessed pre- and post-FastFES while walking without stimulation.Results:Two participants (R1, R2) were categorized as responders based on improvements in clinical walking function. Consistent with heterogeneity of clinical and biomechanical changes commonly observed following gait rehabilitation, how muscle activity was altered with FastFES differed between responders. R1 exhibited improved plantarflexor recruitment during stance accompanied by increased paretic propulsion. R2 exhibited improved dorsiflexor recruitment during swing accompanied by improved paretic ankle angle at initial-contact. In contrast, the third participant (NR1), classified as a non-responder, demonstrated increased ankle muscle activity during inappropriate phases of the gait cycle. Across all participants, there was a positive relationship between increased walking speeds after FastFES and reduced SOL/TA muscle coactivation.Conclusion:Our preliminary case series study is the first to demonstrate that improvements in ankle plantarflexor and dorsiflexor muscle recruitment (muscles targeted by FastFES) accompanied improvements in gait biomechanics and walking function following FastFES in individuals post-stroke. Our results also suggest that inducing more appropriate (i.e., reduced) ankle plantar/dorsi-flexor muscle coactivation may be an important neuromuscular mechanism underlying improvements in gait function after FastFES training, suggesting that pre-treatment ankle muscle status could be used for inclusion into FastFES. The findings of this case-series study, albeit preliminary, provide the rationale and foundations for larger-sample studies using similar methodology.