Discovery of MK-1439, an orally bioavailable non-nucleoside reverse transcriptase inhibitor potent against a wide range of resistant mutant HIV viruses.

The optimization of a novel series of non-nucleoside reverse transcriptase inhibitors (NNRTI) led to the identification of pyridone 36. In cell cultures, this new NNRTI shows a superior potency profile against a range of wild type and clinically relevant, resistant mutant HIV viruses. The overall favorable preclinical pharmacokinetic profile of 36 led to the prediction of a once daily low dose regimen in human. NNRTI 36, now known as MK-1439, is currently in clinical development for the treatment of HIV infection.

Changes in activation timing of knee and ankle extensors during gait are related to changes in heteronymous spinal pathways after stroke.

BACKGROUND: Extensor synergy is often observed in the paretic leg of stroke patients. Extensor synergy consists of an abnormal stereotyped co-activation of the leg extensors as patients attempt to move. As a component of this synergy, the simultaneous activation of knee and ankle extensors in the paretic leg during stance often affects gait pattern after stroke. The mechanisms involved in extensor synergy are still unclear. The first objective of this study is to compare the co-activation of knee and ankle extensors during the stance phase of gait between stroke and healthy individuals. The second objective is to explore whether this co-activation is related to changes in heteronymous spinal modulations between quadriceps and soleus muscles on the paretic side in post-stroke individuals. METHODS: Thirteen stroke patients and ten healthy individuals participated in gait and heteronymous spinal modulation evaluations. Co-activation was measured using peak EMG activation intervals (PAI) and co-activation amplitude indexes (CAI) between knee and ankle extensors during the stance phase of gait in both groups. The evaluation of heteronymous spinal modulations was performed on the paretic leg in stroke participants and on one leg in healthy participants. This evaluation involved assessing the early facilitation and later inhibition of soleus voluntary EMG induced by femoral nerve stimulation. RESULTS: All PAI were lower and most CAI were higher on the paretic side of stroke participants compared with the co-activation indexes among control participants. CAI and PAI were moderately correlated with increased heteronymous facilitation of soleus on the paretic side in stroke individuals. CONCLUSIONS: Increased co-activation of knee and ankle extensors during gait is related to changes in intersegmental facilitative pathways linking quadriceps to soleus on the paretic side in stroke individuals. Malfunction of intersegmental pathways could contribute to abnormal timing of leg extensors during the stance phase of gait in hemiparetic individuals.

Design and validation of an intelligent wheelchair towards a clinically-functional outcome.

BACKGROUND: Many people with mobility impairments, who require the use of powered wheelchairs, have difficulty completing basic maneuvering tasks during their activities of daily living (ADL). In order to provide assistance to this population, robotic and intelligent system technologies have been used to design an intelligent powered wheelchair (IPW). This paper provides a comprehensive overview of the design and validation of the IPW. METHODS: The main contributions of this work are three-fold. First, we present a software architecture for robot navigation and control in constrained spaces. Second, we describe a decision-theoretic approach for achieving robust speech-based control of the intelligent wheelchair. Third, we present an evaluation protocol motivated by a meaningful clinical outcome, in the form of the Robotic Wheelchair Skills Test (RWST). This allows us to perform a thorough characterization of the performance and safety of the system, involving 17 test subjects (8 non-PW users, 9 regular PW users), 32 complete RWST sessions, 25 total hours of testing, and 9 kilometers of total running distance. RESULTS: User tests with the RWST show that the navigation architecture reduced collisions by more than 60% compared to other recent intelligent wheelchair platforms. On the tasks of the RWST, we measured an average decrease of 4% in performance score and 3% in safety score (not statistically significant), compared to the scores obtained with conventional driving model. This analysis was performed with regular users that had over 6 years of wheelchair driving experience, compared to approximately one half-hour of training with the autonomous mode. CONCLUSIONS: The platform tested in these experiments is among the most experimentally validated robotic wheelchairs in realistic contexts. The results establish that proficient powered wheelchair users can achieve the same level of performance with the intelligent command mode, as with the conventional command mode.

Abnormal coactivation of knee and ankle extensors is related to changes in heteronymous spinal pathways after stroke.

BACKGROUND: Abnormal coactivation of leg extensors is often observed on the paretic side of stroke patients while they attempt to move. The mechanisms underlying this coactivation are not well understood. This study (1) compares the coactivation of leg extensors during static contractions in stroke and healthy individuals, and (2) assesses whether this coactivation is related to changes in intersegmental pathways between quadriceps and soleus (Sol) muscles after stroke. METHODS: Thirteen stroke patients and ten healthy individuals participated in the study. Levels of coactivation of knee extensors and ankle extensors were measured in sitting position, during two tasks: maximal isometric voluntary contractions in knee extension and in plantarflexion. The early facilitation and later inhibition of soleus voluntary EMG evoked by femoral nerve stimulation were assessed in the paretic leg of stroke participants and in one leg of healthy participants. RESULTS: Coactivation levels of ankle extensors (mean ± SEM: 56 ± 7% of Sol EMG max) and of knee extensors (52 ± 10% of vastus lateralis (VL) EMG max) during the knee extension and the ankle extension tasks respectively were significantly higher in the paretic leg of stroke participants than in healthy participants (26 ± 5% of Sol EMG max and 10 ± 3% of VL EMG max, respectively). Early heteronymous facilitation of Sol voluntary EMG in stroke participants (340 ± 62% of Sol unconditioned EMG) was significantly higher than in healthy participants (98 ± 34%). The later inhibition observed in all control participants was decreased in the paretic leg. Levels of coactivation of ankle extensors during the knee extension task were significantly correlated with both the increased facilitation (Pearson r = 0.59) and the reduced inhibition (r = 0.56) in the paretic leg. Measures of motor impairment were more consistently correlated with the levels of coactivation of biarticular muscles than those of monoarticular muscles. CONCLUSION: These results suggest that the heteronymous pathways linking quadriceps to soleus may participate in the abnormal coactivation of knee and ankle extensors on the paretic side of stroke patients. The motor impairment of the paretic leg is strongly associated with the abnormal coactivation of biarticular muscles.

Dynamic Visual Stimulations Produced in a Controlled Virtual Reality Environment Reveals Long-Lasting Postural Deficits in Children With Mild Traumatic Brain Injury.

Motor control deficits outlasting self-reported symptoms are often reported following mild traumatic brain injury (mTBI). The exact duration and nature of these deficits remains unknown. The current study aimed to compare postural responses to static or dynamic virtual visual inputs and during standard clinical tests of balance in 38 children between 9 and 18 years-of-age, at 2 weeks, 3 and 12 months post-concussion. Body sway amplitude (BSA) and postural instability (vRMS) were measured in a 3D virtual reality (VR) tunnel (i.e., optic flow) moving in the antero-posterior direction in different conditions. Measures derived from standard clinical balance evaluations (BOT-2, Timed tasks) and post-concussion symptoms (PCSS-R) were also assessed. Results were compared to those of 38 healthy non-injured children following a similar testing schedule and matched according to age, gender, and premorbid level of physical activity. Results highlighted greater postural response with BSA and vRMS measures at 3 months post-mTBI, but not at 12 months when compared to controls, whereas no differences were observed in post-concussion symptoms between mTBI and controls at 3 and 12 months. These deficits were specifically identified using measures of postural response in reaction to 3D dynamic visual inputs in the VR paradigm, while items from the BOT-2 and the 3 timed tasks did not reveal deficits at any of the test sessions. PCSS-R scores correlated between sessions and with the most challenging condition of the BOT-2 and as well as with the timed tasks, but not with BSA and vRMS. Scores obtained in the most challenging conditions of clinical balance tests also correlated weakly with BSA and vRMS measures in the dynamic conditions. These preliminary findings suggest that using 3D dynamic visual inputs such as optic flow in a controlled VR environment could help detect subtle postural impairments and inspire the development of clinical tools to guide rehabilitation and return to play recommendations.

Control of wrist position and muscle relaxation by shifting spatial frames of reference for motoneuronal recruitment: possible involvement of corticospinal pathways.

It has previously been established that muscles become active in response to deviations from a threshold (referent) position of the body or its segments, and that intentional motor actions result from central shifts in the referent position. We tested the hypothesis that corticospinal pathways are involved in threshold position control during intentional changes in the wrist position in humans. Subjects moved the wrist from an initial extended to a final flexed position (and vice versa). Passive wrist muscle forces were compensated with a torque motor such that wrist muscle activity was equalized at the two positions. It appeared that motoneuronal excitability tested by brief muscle stretches was also similar at these positions. Responses to mechanical perturbations before and after movement showed that the wrist threshold position was reset when voluntary changes in the joint angle were made. Although the excitability of motoneurons was similar at the two positions, the same transcranial magnetic stimulus (TMS) elicited a wrist extensor jerk in the extension position and a flexor jerk in the flexion position. Extensor motor-evoked potentials (MEPs) elicited by TMS at the wrist extension position were substantially bigger compared to those at the flexion position and vice versa for flexor MEPs. MEPs were substantially reduced when subjects fully relaxed wrist muscles and the wrist was held passively in each position. Results suggest that the corticospinal pathway, possibly with other descending pathways, participates in threshold position control, a process that pre-determines the spatial frame of reference in which the neuromuscular periphery is constrained to work. This control strategy would underlie not only intentional changes in the joint position, but also muscle relaxation. The notion that the motor cortex may control motor actions by shifting spatial frames of reference opens a new avenue in the analysis and understanding of brain function.

The effect of sex and chronic low back pain on back muscle reflex responses.

Different back muscle reflex assessment protocols have shown abnormally longer reflex latency responses of back muscles in chronic low back pain (CLBP). However, many confounding variables are difficult to control, such as the load magnitude and the preactivation of trunk muscles. The aims of this study were to evaluate, in 30 subjects with CLBP and 30 healthy controls, the activation levels of back muscles during pre-loading and their reflex responses to sudden loading. After subjected to six practice perturbations, 20 sudden and unexpected forward perturbations of the trunk were applied in 30 CLBP subjects (14 women) and 31 controls (17 women), while attempting to minimize the confounding effect of preactivation level and perturbation amplitude. Reflex latency and amplitudes were computed from the surface EMG signals of four back muscles (bilaterally at L5, L3, L1, T10 vertebral levels). EMG was also collected from abdominal muscles. Subjects with CLBP significantly increased the preactivation of back muscles (abdominal preactivation the same) relative to controls while no sex effect was observed. While adjusting statistically for these differences, reflex amplitude was significantly higher in subjects with CLBP and men, compared to healthy controls and women, respectively. Interestingly, contrary to most of the literature available, no between-group effects were detected for reflex latency, which could potentially be explained by an appropriate control of confounding variables, but this remains to be clarified in future research.

Using activity diaries to measure children's and adolescents' compliance with activity restrictions after mild traumatic brain injury.

PURPOSE: To examine the extent to which children and adolescents with a mild traumatic brain injury (MTBI) comply with the activity restrictions received upon discharge from a pediatric trauma center. PARTICIPANTS: Thirty-four children with MTBI (aged 8-16 years) and 34 control children matched for age, sex, and premorbid level of physical activity. MAIN MEASURE: Activity diary documenting the exact level of activity during 3 consecutive days during the 1st, 4th, and 12th week post-MTBI (corresponding time intervals for controls) and the Physical Activity Questionnaire. RESULTS: Fifteen pairs of children (MTBI + control) completed the diaries for all 3 assessment times (77% participation rate among consecutive admissions and 44% compliance rate with diary completion). Although some children engaged in activities before the end of the 4-week restriction period, the majority of the children followed the recommendations they received. Children with MTBI maintained a lower level of energy expenditure at the 1- and 4-week evaluations than did the noninjured children, but not at the 12-week evaluation. CONCLUSION: Children with MTBI usually comply with the activity restrictions they receive upon discharge from the hospital.

Mild traumatic brain injury induces prolonged visual processing deficits in children.

PRIMARY OBJECTIVE: To compare the sensitivity to simple and complex visual stimuli of children who have sustained a mild traumatic brain injury (mTBI) to that of matched non-injured children and to determine the evolution of visuo-perceptual performance over time. RESEARCH DESIGN: A prospective design was used to assess 18 children with mTBI and 18 matched healthy controls (8-16 years of age). METHODS AND PROCEDURES: Sensitivity to static and dynamic forms of simple (first-order) and complex (second-order) stimuli were assessed at 1, 4 and 12 weeks post-injury and at equivalent times for controls. Orientation and direction identification thresholds were measured for all participants for static and dynamic conditions, respectively. In addition, sensitivity to radial optic flow (inward vs outward), a complex motion stimulus, was assessed. MAIN OUTCOMES AND RESULTS: Thresholds measured from all complex stimuli were significantly affected for the mTBI children over time whereas no difference in threshold between groups across all testing conditions was found for simple, first-order information. Sensitivity to all complex stimuli was still affected 12 weeks after the injury. CONCLUSION: These findings suggest that injured children present selective processing deficits for higher-order information and that this deficit persists over relatively long periods. Such measures could be useful to assess children who have sustained mTBI and possibly contribute to identifying potential risks of returning these children to demanding physical activities.

Patellar tendon vibration reduces the increased facilitation from quadriceps to soleus in post-stroke hemiparetic individuals.

BACKGROUND: Stimulation of the femoral nerve in healthy people can facilitate soleus H-reflex and electromyography (EMG) activity. In stroke patients, such facilitation of transmission in spinal pathways linking the quadriceps and soleus muscles is enhanced and related to co-activation of knee and ankle extensors while sitting and walking. Soleus H-reflex facilitation can be depressed by vibration of the quadriceps in healthy people, but the effects of such vibration have never been studied on the abnormal soleus facilitation observed in people after stroke. OBJECTIVES: To determine whether vibration of the quadriceps can modify the enhanced heteronymous facilitation of the soleus muscle observed in people with spastic stroke after femoral nerve stimulation and compare post-vibration effects on soleus facilitation in control and stroke individuals. METHODS: Modulation of voluntary soleus EMG activity induced by femoral nerve stimulation (2×motor threshold) was assessed before, during and after vibration of the patellar tendon in 10 healthy controls and 17 stroke participants. RESULTS: Voluntary soleus EMG activity was facilitated by femoral nerve stimulation in 4/10 (40%) controls and 11/17 (65%) stroke participants. The level of facilitation was greater in the stroke than control group. Vibration significantly reduced early heteronymous facilitation in both groups (50% of pre-vibration values). However, the delay in recovery of soleus facilitation after vibration was shorter for the stroke than control group. The control condition with the vibrator turned off had no effect on the modulation. CONCLUSIONS: Patellar tendon vibration can reduce the facilitation between knee and ankle extensors, which suggests effective presynaptic inhibition but decreased post-activation depression in the lower limb of people after chronic hemiparetic stroke. Further studies are warranted to determine whether such vibration could be used to reduce the abnormal extension synergy of knee and ankle extensors in people after hemiparetic stroke.

A Brain Penetrant Mutant IDH1 Inhibitor Provides In Vivo Survival Benefit.

Mutations in IDH1 are highly prevalent in human glioma. First line treatment is radiotherapy, which many patients often forego to avoid treatment-associated morbidities. The high prevalence of IDH1 mutations in glioma highlights the need for brain-penetrant IDH1 mutant-selective inhibitors as an alternative therapeutic option. Here, we have explored the utility of such an inhibitor in IDH1 mutant patient-derived models to assess the potential therapeutic benefits associated with intracranial 2-HG inhibition. Treatment of mutant IDH1 cell line models led to a decrease in intracellular 2-HG levels both in vitro and in vivo. Interestingly, inhibition of 2-HG production had no effect on in vitro IDH1 mutant glioma cell proliferation. In contrast, IDH1 mutant-selective inhibitors provided considerable survival benefit in vivo. However, even with near complete inhibition of intratumoral 2-HG production, not all mutant glioma models responded to treatment. The results suggest that disruption of 2-HG production with brain-penetrant inhibitors in IDH1 mutant gliomas may have substantial patient benefit.

Excipient quantitation and drug distribution during formulation optimization.

An oral granules formulation experienced high drug content and increased variability when the process was scaled up from lab scale to clinical manufacturing scale. It was suspected that mannitol, due to its smaller particle size and lower density, was preferentially lost during the top spray granulation process, thereby causing active enrichment in the remaining granules. In order to troubleshoot the problem, rapidly evaluate solutions, and further optimize the formulation, a simple and rapid analytical technique was required. Since mannitol does not have a UV chromophore, conventional HPLC/UV analysis could not be used. Three alternative analytical techniques were evaluated in terms of ease of use, reproducibility, linear dynamic range and rapidity. The HPLC/RID (refractive index detector) and HPLC/ELSD (evaporative light scattering detector) provided rapid, reproducible alternate techniques to HPLC/UV, whereas LC/MS showed poor reproducibility. Analysis of the sieve samples of the granulations by HPLC/RID and HPLC/ELSD confirmed that poor active drug distribution was due to mannitol losses in the filter bag, as well as increased low size granules low in active drug content. The resultant formulation process was modified and a reduction in the initial air flow at start-up reduced losses of mannitol in the granulator filters.

First- and Second-Order Stimuli Reaction Time Measures Are Highly Sensitive to Mild Traumatic Brain Injuries.

Mild traumatic brain injury (mTBI) has subtle effects on several brain functions that can be difficult to assess and follow up. We investigated the impact of mTBI on the perception of sine-wave gratings defined by first- and second-order characteristics. Fifteen adults diagnosed with mTBI were assessed at 15 days, 3 months, and 12 months postinjury. Fifteen matched controls followed the same testing schedule. Reaction times (RTs) for flicker detection and motion direction discrimination were measured. Stimulus contrast of first- and second-order patterns was equated to control for visibility, and correct-response RT means, standard deviations (SDs), medians, and interquartile ranges (IQRs) were calculated. The level of symptoms was also evaluated to compare it to RT data. In general in mTBI, RTs were longer, and SDs as well as IQRs larger, than those of controls. In addition, mTBI participants' RTs to first-order stimuli were shorter than those to second-order stimuli, and SDs as well as IQRs larger for first- than for second-order stimuli in the motion condition. All these observations were made over the three sessions. The level of symptoms observed in mTBI was higher than that of control participants, and this difference did also persist up to 1 year after the brain injury, despite an improvement. The combination of RT measures with particular stimulus properties is a highly sensitive method for measuring mTBI-induced visuomotor anomalies and provides a fine probe of the underlying mechanisms when the brain is exposed to mild trauma.

The utilization of activity-based cost accounting in hospitals.

Healthcare costs are being examined on all fronts. Healthcare accounts for 11% of the gross national product and will continue to rise as the "babyboomers" reach retirement age. While ascertaining costs is important, most research shows that costing methods have not been implemented in hospitals. This study is concerned with the use of costing methods; particularly activity-based cost accounting. A mail survey of CFOs was undertaken to determine the type of cost accounting method they use. In addition, they were asked whether they were aware of activity-based cost accounting and whether they had implemented it or were planning to implement it. Only 71.8% were aware of it and only 4.7% had implemented it. In addition, only 52% of all hospitals report using any cost accounting systems. Education needs to ensure that all healthcare executives are cognizant of activity-based accounting and its importance in determining costs. Only by determining costs can hospitals strive to contain them.

The potential impact of intelligent power wheelchair use on social participation: perspectives of users, caregivers and clinicians.

PURPOSE: To explore power wheelchair users', caregivers' and clinicians' perspectives regarding the potential impact of intelligent power wheelchair use on social participation. METHODS: Semi-structured interviews were conducted with power wheelchair users (n = 12), caregivers (n = 4) and clinicians (n = 12). An illustrative video was used to facilitate discussion. The transcribed interviews were analyzed using thematic analysis. RESULTS: Three main themes were identified based on the experiences of the power wheelchair users, caregivers and clinicians: (1) increased social participation opportunities, (2) changing how social participation is experienced and (3) decreased risk of accidents during social participation. CONCLUSION: Findings from this study suggest that an intelligent power wheelchair would enhance social participation in a variety of important ways, thereby providing support for continued design and development of this assistive technology. IMPLICATIONS FOR REHABILITATION: An intelligent power wheelchair has the potential to: Increase social participation opportunities by overcoming challenges associated with navigating through crowds and small spaces. Change how social participation is experienced through "normalizing" social interactions and decreasing the effort required to drive a power wheelchair. Decrease the risk of accidents during social participation by reducing the need for dangerous compensatory strategies and minimizing the impact of the physical environment.

Botulinum toxin improves lid opening delays in blepharospasm-associated apraxia of lid opening.

Lid movement and EMG of the orbicularis oculi (OOc) were analyzed in 10 patients with apraxia of lid opening associated with blepharospasm before and after botulinum toxin treatment. The latencies to onset and to complete the eye opening and the time during which eye opening was sustained were studied in relation to OOc activity and compared with control values obtained in 12 healthy subjects. Following treatment there was an improvement of all lid opening measurements, a decrease of the abnormally prolonged OOc activity, and a reduction of the functional disability.

Tactile, thermal and pain sensibility in burned patients with and without chronic pain and paresthesia problems.

Abnormal return of cutaneous sensibility is common after burn injuries and many patients complain of painful and/or paresthetic sensations in their healed wounds. However, little is known about the exact nature and severity of these problems. The present study was designed to provide a quantitative evaluation of the cutaneous sensibility in burned patients. Tactile, thermal and pain thresholds were measured in 121 patients with healed burns paired-matched to 121 control healthy subjects more than 18 months after the burns. Testing was confined to both upper limbs and was performed in a healed burn area and its contralateral burned or unburned counterpart. The tested sites were also divided into symptomatic and asymptomatic ones, depending on the presence or not of pain or paresthesia at the site. The results showed significantly higher sensory thresholds in burned patients than control subjects. Severity of the deficits of the various sensory modalities was, however, a function of burn depth. Deep burn injuries which had required skin grafts to heal were more seriously affected than superficial burns which had healed spontaneously. Significant sensory losses were found not only in burn sites but also in the non-injured areas suggesting changes in the central nervous system. When symptomatic and asymptomatic sites were compared, significant deficits were observed in the tactile modality (touch-pressure). Other significant predictors of chronic sensory problems were burn depth and patients' age. Pathophysiological mechanisms of diminished sensibility in burned and unburned skin as long as several years after the injury are discussed along with those implicated in pain and paresthesia problems reported by the patients.

Motor unit firing pattern, synchrony and coherence in a deafferented patient.

The firing of spinal motoneurons (MNs) is controlled continuously by inputs from muscle, joint and skin receptors. Besides altering MN synaptic drive, the removal of these inputs is liable to alter the synaptic noise and, thus, the variability of their tonic activity. Sensory afferents, which are a major source of common and/or synchronized inputs shared by several MNs, may also contribute to the coupling in the time and frequency domains (synchrony and coherence, respectively) observed when cross-correlation and coherence analyses are applied to the discharges of MN pairs. Surprisingly, no consistent changes in firing frequency, nor in synchrony and coherence were reported to affect the activity of 3 pairs of motor units (MUs) tested in a case of sensory polyradiculoneuropathy (SPRNP), leading to an irreversible loss of large diameter sensory afferents (Farmer et al., 1993). Such a limited sample, however, precludes a definite conclusion about the actual impact that a chronic loss of muscle and cutaneous afferents may have on the firing properties of human MUs. To address this issue, the firing pattern of 92 MU pairs was analyzed at low contraction force in a case of SPRNP leading similarly to a permanent loss of proprioceptive inputs. Compared with 8 control subjects, MNs in this patient tended to discharge with slightly shorter inter-spike intervals but with greater variability. Synchronous firing tended to occur more frequently with a tighter coupling in the patient. There was no consistent change in coherence in the 15-30 Hz frequency range attributed to the MN corticospinal drive, but a greater coherence was observed below 5 Hz and between 30 and 60 Hz in the patient. The possible origins of the greater irregularity in MN tonic discharges, the tighter coupling of the synchronous firing and the changes in coherence observed in the absence of proprioceptive inputs are discussed.

Complex muscle vibration patterns to induce gait-like lower-limb movements: proof of concept.

Muscle vibrations can induce motor responses and illusions of complex movements. However, inducing gait-like cyclical movements and illusions requires the application of multiple fast alternating vibrations to lower-limb muscles. The objectives were (1) to test the feasibility of delivering complex vibrations in a time-organized manner and (2) to illustrate the possibility of inducing alternate gait-in-place-like movements using these vibrations. Patterns of vibration, produced by 12 vibrators applied bilaterally on the flexor and extensor muscle groups of the lower limbs, were based on normal gait kinematics. We tested 1 s and 2 s cycle patterns of vibration. Vibrator responses were assessed using auto- and crosscorrelations and frequency analyses based on accelerometry measurements, and compared between patterns. High auto- (>0.8) and crosscorrelation (>0.6) coefficients demonstrated a good response by the vibrators to the control signal. Vibrations induced cyclical, low-amplitude stepping-in-place movements that mimicked alternate walking movements with both legs, with 1 s and 2 s cycle durations, in one nondisabled participant and one participant with American Spinal Injury Association Impairment Scale B spinal cord injury standing, relaxed, with body-weight support. Electromechanical vibrators can deliver complex cyclical vibrations and trigger gait-like lower-limb movements. These results warrant the application of these vibration patterns on individuals with sensorimotor impairments to test their potential in gait rehabilitation.

Exploring powered wheelchair users and their caregivers' perspectives on potential intelligent power wheelchair use: a qualitative study.

Power wheelchairs (PWCs) can have a positive impact on user well-being, self-esteem, pain, activity and participation. Newly developed intelligent power wheelchairs (IPWs), allowing autonomous or collaboratively-controlled navigation, could enhance mobility of individuals not able to use, or having difficulty using, standard PWCs. The objective of this study was to explore the perspectives of PWC users (PWUs) and their caregivers regarding if and how IPWs could impact on current challenges faced by PWUs, as well as inform current development of IPWs. A qualitative exploratory study using individual interviews was conducted with PWUs (n = 12) and caregivers (n = 4). A semi-structured interview guide and video were used to facilitate informed discussion regarding IPWs. Thematic analysis revealed three main themes: (1) "challenging situations that may be overcome by an IPW" described how the IPW features of obstacle avoidance, path following, and target following could alleviate PWUs' identified mobility difficulties; (2) "cautious optimism concerning IPW use revealed participants" addresses concerns regarding using an IPW as well as technological suggestions; (3) "defining the potential IPW user" revealed characteristics of PWUs that would benefit from IPW use. Findings indicate how IPW use may help overcome PWC difficulties and confirm the importance of user input in the ongoing development of IPWs.