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Background: Reaching is a fundamental motor skill often impaired in cerebral palsy (CP). Studies on manual function, intervention, and underlying brain mechanisms largely focus on unilateral CP. This first electroencephalography (EEG) evaluation of reaching exclusively in bilateral CP aims to quantify and relate brain activation patterns to bimanual deficits in this population., Methods: A total of 15 children with bilateral CP (13.4 ± 2.9 years) and 13 with typical development (TD: 14.3 ± 2.4 years) performed 45 reaches per hand while recording motion capture and EEG data. The Box and Blocks test was administered bilaterally. Cortical sources were identified using independent component analysis and clustered using k -means. Alpha (8-12 Hz) and beta (13-30 Hz) band event-related desynchronization (ERD) values were compared across groups and hands within clusters, between dominant and non-dominant sensorimotor clusters, and related to reach kinematics and the Box and Block test., Results: The group with CP demonstrated bimanual motor deficits with slower reaches, lower Box and Blocks scores, and stronger hand preference than in TD. Beta ERD, representing motor execution, was notably higher in the dominant sensorimotor cluster in CP compared to TD. Both groups demonstrated more contralateral than ipsilateral activity in both hands and clusters, with CP showing a less lateralized (more bilateral) alpha response. Higher brain activation was generally related to better function., Conclusion: Bimanual deficits in bilateral CP and related EEG differences warrant more clinical and research attention particularly earlier in life when greater potential for neural and functional recovery exists.

Objective: Few studies focus on upper limbs in bilateral cerebral palsy (CP) despite potential bimanual deficits. Electroencephalography (EEG) was utilized to investigate brain mechanisms underlying upper limb tasks in bilateral CP and typical development (TD) and relationships to function., Methods: 26 (14 CP; 12 TD) completed the Box and Blocks Test and transport task with paper, sponge or mixed blocks, while recording EEG and motion data., Results: Group effects for path time, path length and Box and Blocks Test revealed bimanual deficits. Four sensorimotor-related EEG clusters were identified. Group effects were found in premotor and dominant motor clusters with greater beta event-related desynchronization (ERD) in CP. Hand and hand by group effects were found in the dominant motor cluster, showing greater ERD with the more affected hand in CP. Condition effects were prominent in the posterior parietal cluster with higher ERD reflecting greater difficulty in force modulation., Conclusions: Higher brain activation associated with greater bimanual deficits is similar to our lower limb findings but contrasts studies in TD or unilateral CP linking higher ERD to greater proficiency., Significance: Bilateral CP shows overreliance on the dominant hemisphere with the less functional hand and higher brain activity presumably related to excessive intracortical connectivity., Competing Interests: Disclosure None of the authors has any disclosures or conflicts related to this manuscript., (Published by Elsevier B.V.)

Background: Progressive supranuclear palsy (PSP) is a neurodegenerative condition, typically presenting with, but not limited to, impairments of postural instability, gait, and gaze stability., Purpose: This case report describes the multifactorial assessment and rehabilitation of a patient with atypical PSP who has significant gaze deficits, asymmetrical stepping responses, trunk rigidity, and reduced posterior excursion on limits of stability., Case Description: Evaluation utilized computerized gait and balance assessments, foot clearance analysis, a squat test, and a timed stepping test. The intervention included boxing, stepping tasks, and treadmill training each with eye movement challenges. A total of 15 hours of physical therapy was provided; 1 hour, 2 times a week., Outcomes: Post-intervention improvements were noted subjectively, on eye-body coordination, and objectively, on limits of stability, foot clearance, and task performance (squats, timed stepping). Follow-up demonstrated some decline from posttest results; however, patient-reported adherence to the program was less than recommended., Conclusion: A multifactorial rehabilitation program can improve balance, eye-body coordination, and strength in a high functioning patient with atypical PSP. Longitudinal randomized controlled studies are suggested to further investigate this interventional approach in high functioning individuals diagnosed with atypical PSP.

Background: Compared to unilateral cerebral palsy (CP), less is known about brain reorganization and plasticity in bilateral CP especially in relation or response to motor training. The few trials that reported brain imaging results alongside functional outcomes include a handful of studies in unilateral CP, and one pilot trial of three children with bilateral CP. This study is the first locomotor training randomized controlled trial (RCT) in bilateral CP to our knowledge reporting brain imaging outcomes., Methods: Objective was to compare MRI brain volumes, resting state connectivity and white matter integrity using DTI in children with bilateral CP with PVL and preterm birth history (<34 weeks), to age-related controls, and from an RCT of intensive 12 week rapid-reciprocal locomotor training using an elliptical or motor-assisted cycle. We hypothesized that connectivity in CP compared to controls would be greater across sensorimotor-related brain regions and that functional (resting state) and structural (fractional anisotropy) connectivity would improve post intervention. We further anticipated that baseline and post-intervention imaging and functional measures would correlate., Results: Images were acquired with a 3T MRI scanner for 16/27 children with CP in the trial, and 18 controls. No conclusive evidence of training-induced neuroplastic effects were seen. However, analysis of shared variance revealed that greater increases in precentral gyrus connectivity with the thalamus and pons may be associated with larger improvements in the trained device speed. Exploratory analyses also revealed interesting potential relationships between brain integrity and multiple functional outcomes in CP, with functional connectivity between the motor cortex and midbrain showing the strongest potential relationship with mobility. Decreased posterior white matter, corpus callosum and thalamic volumes, and FA in the posterior thalamic radiation were the most prominent group differences with corticospinal tract differences notably not found., Conclusions: Results reinforce the involvement of sensory-related brain areas in bilateral CP. Given the wide individual variability in imaging results and clinical responses to training, a greater focus on neural and other mechanisms related to better or worse outcomes is recommended to enhance rehabilitation results on a patient vs. group level., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Damiano, Pekar, Mori, Faria, Ye, Stashinko, Stanley, Alter, Hoon and Chin.)

Background: Accurate source localization from electroencephalography (EEG) requires electrode co-registration to brain anatomy, a process that depends on precise measurement of 3D scalp locations. Stylus digitizers and camera-based scanners for such measurements require the subject to remain still and therefore are not ideal for young children or those with movement disorders., New Method: Motion capture accurately measures electrode position in one frame but marker placement adds significant setup time, particularly in high-density EEG. We developed an algorithm, named MoLo and implemented as an open-source MATLAB toolbox, to compute 3D electrode coordinates from a subset of positions measured in motion capture using spline interpolation. Algorithm accuracy was evaluated across 5 different-sized head models., Results: MoLo interpolation reduced setup time by approximately 10 min for 64-channel EEG. Mean electrode interpolation error was 2.95 ± 1.3 mm (range: 0.38-7.98 mm). Source localization errors with interpolated compared to true electrode locations were below 1 mm and 0.1 mm in 75 % and 35 % of dipoles, respectively., Comparison With Existing Methods: MoLo location accuracy is comparable to stylus digitizers and camera-scanners, common in clinical research. The MoLo algorithm could be deployed with other tools beyond motion capture, e.g., a stylus, to extract high-density EEG electrode locations from a subset of measured positions. The algorithm is particularly useful for research involving young children and others who cannot remain still for extended time periods., Conclusions: Electrode position and source localization errors with MoLo are similar to other modalities supporting its use to measure high-density EEG electrode positions in research and clinical settings., (Published by Elsevier B.V.)

Background: A cost effective and efficient diagnostic tool for COVID-19 as near to the point of care (PoC) as possible would be a game changer in the current pandemic. We tested reverse transcription loop mediated isothermal amplification (RT-LAMP), a method which can produce results in under 30 min, alongside standard methods in a real-life clinical setting., Methods: This prospective service improvement project piloted an RT-LAMP method on nasal and pharyngeal swabs on 21 residents of a high dependency care home, with two index COVID-19 cases, and compared it to multiplex tandem reverse transcription polymerase chain reaction (RT-PCR). We recorded vital signs of patients to correlate clinical and laboratory information and calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of a single swab using RT-LAMP compared with the current standard, RT-PCR, as per Standards for Reporting Diagnostic Accuracy Studies (STARD) guidelines., Results: The novel method accurately detected 8/10 RT-PCR positive cases and identified a further 3 positive cases. Eight further cases were negative using both methods. Using repeated RT-PCR as a "gold standard", the sensitivity and specificity of a single novel test were 80 and 73% respectively. PPV was 73% and NPV was 83%. Incorporating retesting of low signal RT-LAMP positives improved the specificity to 100%. We also speculate that hypothermia may be a significant early clinical sign of COVID-19., Conclusions: RT-LAMP testing for SARS-CoV-2 was found to be promising, fast and to work equivalently to RT-PCR methods. RT-LAMP has the potential to transform COVID-19 detection, bringing rapid and accurate testing to the PoC. RT-LAMP could be deployed in mobile community testing units, care homes and hospitals to detect disease early and prevent spread.

Background: Neuromuscular Electrical Stimulation (NMES) has been utilized for many years in cerebral palsy (CP) with limited success despite its inherent potential for improving muscle size and/or strength, inhibiting or reducing spasticity, and enhancing motor performance during functional activities such as gait. While surface NMES has been shown to successfully improve foot drop in CP and stroke, correction of more complex gait abnormalities in CP such as flexed knee (crouch) gait remains challenging due to the level of stimulation needed for the quadriceps muscles that must be balanced with patient tolerability and the ability to deliver NMES assistance at precise times within a gait cycle., Methods: This paper outlines the design and evaluation of a custom, noninvasive NMES system that can trigger and adjust electrical stimulation in real-time. Further, this study demonstrates feasibility of one possible application for this digitally-controlled NMES system as a component of a pediatric robotic exoskeleton to provide on-demand stimulation to leg muscles within specific phases of the gait cycle for those with CP and other neurological disorders who still have lower limb sensation and volitional control. A graphical user interface was developed to digitally set stimulation parameters (amplitude, pulse width, and frequency), timing, and intensity during walking. Benchtop testing characterized system delay and power output. System performance was investigated during a single session that consisted of four overground walking conditions in a 15-year-old male with bilateral spastic CP, GMFCS Level III: (1) his current Ankle-Foot Orthosis (AFO); (2) unassisted Exoskeleton; (3) NMES of the vastus lateralis; and (4) NMES of the vastus lateralis and rectus femoris. We hypothesized in this participant with crouch gait that NMES triggered with low latency to knee extensor muscles during stance would have a modest but positive effect on knee extension during stance., Results: The system delivers four channels of NMES with average delays of 16.5 ± 13.5 ms. Walking results show NMES to the vastus lateralis and rectus femoris during stance immediately improved mean peak knee extension during mid-stance (p = 0.003*) and total knee excursion (p = 0.009*) in the more affected leg. The electrical design, microcontroller software and graphical user interface developed here are included as open source material to facilitate additional research into digitally-controlled surface stimulation ( github.com/NIHFAB/NMES )., Conclusions: The custom, digitally-controlled NMES system can reliably trigger electrical stimulation with low latency. Precisely timed delivery of electrical stimulation to the quadriceps is a promising treatment for crouch. Our ultimate goal is to synchronize NMES with robotic knee extension assistance to create a hybrid NMES-exoskeleton device for gait rehabilitation in children with flexed knee gait from CP as well as from other pediatric disorders., Trial Registration: clinicaltrials.gov, ID: NCT01961557 . Registered 11 October 2013; Last Updated 27 January 2020.

Objectives: To investigate whether quantitative ultrasound (US) imaging, based on the envelope statistics of the backscattered US signal, can describe muscle properties in typically developing children and those with cerebral palsy (CP)., Methods: Radiofrequency US data were acquired from the rectus femoris muscle of children with CP (n = 22) and an age-matched cohort without CP (n = 14) at rest and during maximal voluntary isometric contraction. A mixture of gamma distributions was used to model the histogram of the echo intensities within a region of interest in the muscle., Results: Muscle in CP had a heterogeneous echo texture that was significantly different from that in healthy controls (P < .001), with larger deviations from Rayleigh scattering. A mixture of 2 gamma distributions showed an excellent fit to the US intensity, and the shape and rate parameters were significantly different between CP and control groups (P < .05). The rate parameters for both the single gamma distribution and mixture of gamma distributions were significantly higher for contracted muscles compared to resting muscles, but there was no significant interaction between these factors (CP and muscle contraction) for a mixed-model analysis of variance., Conclusions: Ultrasound tissue characterization indicates a more disorganized architecture and increased echogenicity in muscles in CP, consistent with previously documented increases in fibrous infiltration and connective tissue changes in this population. Our results indicate that quantitative US can be used to objectively differentiate muscle architecture and tissue properties., (This article has been contributed to by US Government employees and their work is in the public domain in the USA. Published 2018 by the American Institute of Ultrasound in Medicine.)

Background: Patients with brain injuries such as Parkinson's disease or stroke exhibit abnormal gait characteristics especially during gait transitions such as step initiation and turning. Since such transitions could precipitate falls and resultant injuries, evaluation and rehabilitation of non-steady state gait in those patients are important. Whereas body weight supported treadmill training (BWSTT) provides a safe and controlled environment for gait training, it is unable to adequately train for gait transitions since the typical linear treadmill does not allow for changes in walking direction and natural fluctuations in speed., Research Question: This paper verifies if the suggested virtual reality (VR) based walking interface combined with the unidirectional treadmill can stimulate the user to initiate turning gait., Methods: To validate whether initiation of turning was successfully achieved with the proposed walking system, we developed the VR-based walking interface combined with the self-paced treadmill and compared kinematics, kinetics, and muscle activation levels during the VR-based turning and over ground (OG) turning as well as between straight walking and turning within conditions., Results: Despite walking on a linear treadmill, subjects showed significant increases in head rotation, pelvic rotation, right hip abduction, left hip adduction, foot progression, medial-lateral ground reaction forces, right medial hamstring activation level, and changes in step width during the VR turn compared to straight walking., Significance: The developed VR-based turning interface can provide a safe and controlled environment for assessment of turning in healthy controls and may have a potential for assessment and training in patients with neurological disorders., Competing Interests: Conflict of interest statement Declarations of interest: none

Background: Locomotor training using treadmills or robotic devices is commonly utilized to improve gait in cerebral palsy (CP); however, effects are inconsistent and fail to exceed those of equally intense alternatives. Possible limitations of existing devices include fixed nonvariable rhythm and too much limb or body weight assistance., Objective: To quantify and compare effectiveness of a motor-assisted cycle and a novel alternative, an elliptical, in CP to improve interlimb reciprocal coordination through intensive speed-focused leg training., Methods: A total of 27 children with bilateral CP, 5 to 17 years old, were randomized to 12 weeks of 20 minutes, 5 days per week home-based training (elliptical = 14; cycle = 13) at a minimum of 40 revolutions per minute, with resistance added when speed target was achieved. Primary outcomes were self-selected and fastest voluntary cadence on the devices and gait speed. Secondary outcomes included knee muscle strength, and selective control and functional mobility measures., Results: Cadence on trained but not nontrained devices increased, demonstrating task specificity of training and increased exercise capability. Mean gait speed did not increase in either group, nor did parent-reported functional mobility. Knee extensor strength increased in both. An interaction between group and time was seen in selective control with scores slightly increasing for the elliptical and decreasing for the cycle, possibly related to tighter limb coupling with cycling., Conclusions: Task-specific effects were similarly positive across groups, but no transfer was seen to gait or function. Training dose was low (≤20 hours) compared with intensive upper-limb training recommendations and may be insufficient to produce appreciable clinical change.

Background: Obstetrical brachial plexus palsy is a common birth injury to nerves passing through the brachial plexus that may result in structural and functional abnormalities. Individual joint trajectories from kinematic analyses have been used to evaluate the source and extent of abnormalities. Here, two summary measures of limb kinematics were utilized: 1) the Arm Profile Score summarizing upper limb joint kinematic abnormalities from a typical pattern across a task, and 2) the recently developed Multi-joint Coordination Measure using principal component analysis to characterize typical coordination of multiple joints throughout a task and compute deviations in time and space. Our aim was to compare these kinematic measures in persons with and without injury and relate these to clinical and functional scales., Methods: 3D kinematic data from 10 upper limb joints were collected on 15 children and adolescents with obstetrical brachial plexus palsy and 21 controls during a reach-to-grasp task in both limbs. The two kinematic measures were computed and correlated with each other and the Mallet and ABILIHAND-Kids., Findings: Both measures revealed that joint angles primarily contributing to shoulder and wrist motion were most prominently affected in the non-dominant limb in obstetrical brachial plexus palsy, with the Multi-joint Coordination Measure additionally indicating when in the motion coordination worsens. These were moderately interrelated but neither correlated with other scales., Interpretation: The Multi-joint Coordination Measure, while related to the Arm Profile Score, may have additional utility for individualized treatment planning and evaluation of any motor task due to the unique spatial-temporal information provided., (Published by Elsevier Ltd.)

Motor adaptation, or alteration of neural control in response to a perturbation, is a potential mechanism to facilitate motor learning for rehabilitation. Central nervous system deficits are known to affect locomotor adaptation; yet we demonstrated that similar to adults following stroke, children with unilateral brain injuries can adapt step length in response to unilateral leg weighting. Here, we extend our analysis to explore kinematic strategies underlying step length adaptation and utilize dynamical systems approaches to elucidate how neural control may differ in those with hemiplegic CP across legs and compared to typically developing controls. Ten participants with hemiplegic CP and ten age-matched controls participated in this study. Knee and hip joint kinematics were analyzed during unilateral weighting of each leg in treadmill walking to assess adaptation and presence and persistence of after-effects. Peak joint angle displacement was used to represent changes in joint angles during walking. We examined baseline and task-specific variability and local dynamic stability to evaluate neuromuscular control across groups and legs. In contrast to controls, children with unilateral CP had asymmetries in joint angle variability and local dynamic stability at baseline, showing increased variability and reduced stability in the dominant limb. Kinematic variability increased and local stability decreased during weighting of ipsilateral and contralateral limbs in both groups compared to baseline. After weight removal both measures returned to baseline. Analogous to the temporal-spatial results, children with unilateral CP demonstrated similar capability as controls to adapt kinematics to unilateral leg weighting, however, the group with CP differed across sides after weight removal with dominant limb after-effects fading more quickly than in controls. The change in kinematics did not completely return to baseline in the non-dominant limb of the CP group, producing a transient improvement in joint angle symmetry. Recent studies demonstrate that neural control of gait is multi-layered with distinct circuits for different types of walking and for each leg. Remarkably, our results demonstrate that children with unilateral brain injury retain these separate circuits for each leg during walking and, importantly, that those networks can be adapted independently from one another to improve symmetry in the short term.

Introduction : Individuals with cerebral palsy (CP) demonstrate high response variability to motor training insufficiently accounted for by age or severity. We propose here that differences in the inherent ability to learn new motor tasks may explain some of this variability. Damage to motor pathways involving the cerebellum, which may be a direct or indirect effect of the brain injury for many with CP, has been shown to adversely affect the ability to learn new motor tasks and may be a potential explanation. Classic adaptation paradigms that evaluate cerebellar integrity have been utilized to assess adaptation to gait perturbations in adults with stroke, traumatic brain injury and other neurological injuries but not in children with CP. Materials and Methods : A case-control study of 10 participants with and 10 without hemiplegic CP within the age range of 5-20 years was conducted. Mean age of participants in the CP group was slightly but not significantly higher than controls. Step length and swing time adaptation, defined as gradual accommodation to a perturbation, and aftereffects, or maintenance of the accommodation upon removal of the perturbation, to unilateral leg weighing during treadmill gait were quantified to assess group differences in learning. Results : Adaptation and aftereffects were demonstrated in step length across groups with no main effect for group. In CP, the dominant leg had a greater response when either leg was weighted. Swing time accommodated immediately (no adaptation) in the weighted leg only, with the non-dominant leg instead showing a more pronounced response in CP. Discussion : This group of participants with unilateral CP did not demonstrate poorer learning or retention similar to reported results in adult stroke. Deficits, while not found here, may become evident in those with other etiologies or greater severity of CP. Our data further corroborate an observation from the stroke literature that repeated practice of exaggerating the asymmetry (error augmentation), in this case by weighting the more involved or shorter step leg, vs. minimizing it by weighting the less involved or longer step leg (error reduction) may be a useful training strategy to improve step symmetry in unilateral CP.

Accumulating evidence suggests cortical circuits may contribute to control of human locomotion. Here, noninvasive electroencephalography (EEG) recorded from able-bodied volunteers during a novel treadmill walking paradigm was used to assess neural correlates of walking. A systematic processing method, including a recently developed subspace reconstruction algorithm, reduced movement-related EEG artifact prior to independent component analysis and dipole source localization. We quantified cortical activity while participants tracked slow and fast target speeds across two treadmill conditions: an active mode that adjusted belt speed based on user movements and a passive mode reflecting a typical treadmill. Our results reveal frequency specific, multi-focal task related changes in cortical oscillations elicited by active walking. Low γ band power, localized to the prefrontal and posterior parietal cortices, was significantly increased during double support and early swing phases, critical points in the gait cycle since the active controller adjusted speed based on pelvis position and swing foot velocity. These phasic γ band synchronizations provide evidence that prefrontal and posterior parietal networks, previously implicated in visuo-spatial and somotosensory integration, are engaged to enhance lower limb control during gait. Sustained μ and β band desynchronization within sensorimotor cortex, a neural correlate for movement, was observed during walking thereby validating our methods for isolating cortical activity. Our results also demonstrate the utility of EEG recorded during locomotion for probing the multi-regional cortical networks which underpin its execution. For example, the cortical network engagement elicited by the active treadmill suggests that it may enhance neuroplasticity for more effective motor training.

There are several advantages that functional near-infrared spectroscopy (fNIRS) presents in the study of the neural control of human movement. It is relatively flexible with respect to participant positioning and allows for some head movements during tasks. Additionally, it is inexpensive, light weight, and portable, with very few contraindications to its use. This presents a unique opportunity to study functional brain activity during motor tasks in individuals who are typically developing, as well as those with movement disorders, such as cerebral palsy. An additional consideration when studying movement disorders, however, is the quality of actual movements performed and the potential for additional, unintended movements. Therefore, concurrent monitoring of both blood flow changes in the brain and actual movements of the body during testing is required for appropriate interpretation of fNIRS results. Here, we show a protocol for the combination of fNIRS with muscle and kinematic monitoring during motor tasks. We explore gait, a unilateral multi-joint movement (cycling), and two unilateral single-joint movements (isolated ankle dorsiflexion, and isolated hand squeezing). The techniques presented can be useful in studying both typical and atypical motor control, and can be modified to investigate a broad range of tasks and scientific questions.

Treadmills provide a safe and efficient method for gait rehabilitation but treadmill based training paradigms have not been shown to create superior results when compared with traditional physical therapy methods such as overground training. One explanation for this may be that walking at a constant, fixed speed requires little mental engagement from the user, which has been postulated as a key factor in the success of motor learning. To increase mental engagement, we developed a user-driven treadmill control scheme. In this paper we use electroencephalography (EEG) to compare cortical activity during user-driven (active) walking with activity on a normal (passive) treadmill in nine healthy subjects. We used independent component analysis (ICA) to isolate brain activity from artifactual components. We fit equivalent dipole sources to each brain component and clustered these across subjects. Our analysis revealed that relative to the passive treadmill, active walking resulted in statistically significant decreases in spectral power, i.e. desynchronization, in the anterior cingulate, sensorimotor cortices, and posterior parietal lobe of the cortex. These results indicate that user-driven treadmills more fully engage the motor cortex and therefore could facilitate better training outcomes than a traditional treadmill.

Background: Balance problems are common in cerebral palsy (CP) but etiology is often uncertain. The classic Romberg test compares ability to maintain standing with eyes open versus closed. Marked instability without vision is a positive test and generally indicates proprioceptive loss. From previous work showing diminished hip joint proprioception in CP, we hypothesized that static and dynamic balance without vision (positive Romberg) would be compromised in CP., Methods: Force plate sway and gait velocity data were collected using 3D motion capture on 52 participants, 19 with diplegic CP, 13 with hemiplegic CP, and 20 without disability. Center of mass (COM) and center or pressure (COP) velocity, excursion, and differences between COM and COP in AP and ML directions were computed from static standing trials with eyes open and closed. Mean gait velocity with and without dribble glasses was compared. Hip joint proprioception was quantified as the root mean square of magnitude of limb positioning errors during a hip rotation task with and without view of the limb. Mixed model repeated measures analysis of variance (ANOVA) was performed with condition as within-subject (EO, EC) and group as between-subject factors (hemiplegia, diplegia, controls). Sway characteristics and gait speed were correlated with proprioception values., Results: Groups with CP had greater sway in standing with eyes open indicating that they had poorer balance than controls, with the deficit relatively greater in the ML compared to AP direction. Contrary to our hypothesis, the decrement with eyes closed did not differ from controls (negative Romberg); however, proprioception error was related to sway parameters particularly for the non-dominant leg. Gait speed was related to proprioception values such that those with worse proprioception tended to walk more slowly., Conclusions: Postural instability is present even in those with mild CP and is yet another manifestation of their motor control disorder, the specific etiology of which may vary across individuals in this heterogeneous diagnostic category.

A self-paced treadmill that can simulate overground walking has the potential to improve the effectiveness of treadmill training for gait rehabilitation. We have implemented a self-paced treadmill without the need for expensive equipment such as a motion capture system and an instrumented treadmill. For this, an inexpensive depth sensor, ASUS XtionTM, substitutes for the motion capture system, and a low-cost commercial treadmill is considered as the platform of the self-paced treadmill. The proposed self-paced treadmill is also convenient because the depth sensor does not require markers placed on user's body. Through pilot tests with two healthy subjects, it is quantitatively and qualitatively verified that the proposed self-paced treadmill achieves similar performance as one which utilizes a commercial motion capture system (VICON) as well as an instrumented treadmill.

Individuals with cerebral palsy have neurological deficits that may interfere with motor function and lead to abnormal walking patterns. It is important to know the joint moment generated by the patient's muscles during walking in order to assist the suboptimal gait patterns. In this paper, we describe a practical strategy for estimating the internal moment of a knee joint from surface electromyography (sEMG) and knee joint angle measurements. This strategy requires only isokinetic knee flexion and extension tests to obtain a relationship between the sEMG and the knee internal moment, and it does not necessitate comprehensive laboratory calibration, which typically requires a 3-D motion capture system and ground reaction force plates. Four estimation models were considered based on different assumptions about the functions of the relevant muscles during the isokinetic tests and the stance phase of walking. The performance of the four models was evaluated by comparing the estimated moments with the gold standard internal moment calculated from inverse dynamics. The results indicate that an optimal estimation model can be chosen based on the degree of cocontraction. The estimation error of the chosen model is acceptable (normalized root-mean-squared error: 0.15-0.29, R: 0.71-0.93) compared to previous studies (Doorenbosch and Harlaar, 2003; Doorenbosch and Harlaar, 2004; Doorenbosch, Joosten, and Harlaar, 2005), and this strategy provides a simple and effective solution for estimating knee joint moment from sEMG.

Treadmill-based locomotor training should simulate overground walking as closely as possible for optimal skill transfer. The constant speed of a standard treadmill encourages automaticity rather than engagement and fails to simulate the variable speeds encountered during real-world walking. To address this limitation, this paper proposes a user-driven treadmill velocity control scheme that allows the user to experience natural fluctuations in walking velocity with minimal unwanted inertial force due to acceleration/deceleration of the treadmill belt. A smart estimation limiter in the scheme effectively attenuates the inertial force during velocity changes. The proposed scheme requires measurement of pelvic and swing foot motions, and is developed for a treadmill of typical belt length (1.5 m). The proposed scheme is quantitatively evaluated here with four healthy subjects by comparing it with the most advanced control scheme identified in the literature.

The extent to which therapeutic, exercise or robotic devices can maximize gait function is a major unresolved issue in neurorehabilitation. Several factors may influence gait outcomes such as similarity of the task to overground walking, degree of coordination within and across limbs, and cycle-to-cycle variability in each device. Our objective was to compare lower extremity kinematics, coordination and variability during four locomotor tasks: overground walking, treadmill walking, elliptical training and stationary cycling in 10 non-disabled adults (6 male; mean age 22.7±2.9 yrs, range 20-29). All first performed four overground walking trials at self-selected speed with mean temporal-spatial data used to pace the other conditions. Joint positions, excursions, and the Gait Deviation Index (GDI) were compared across conditions to evaluate kinematic similarity. Time-series data were correlated within and across limbs to evaluate intralimb and interlimb coordination, respectively. Variability in cadence was quantified to assess how constrained the locomotor rhythm was compared to overground walking. Treadmill walking most closely resembled overground with GDI values nearly overlapping, reinforcing its appropriateness for gait training. Cycling showed the largest GDI difference from overground, with elliptical closer but still a significant distance from all three. Cycling showed greater hip reciprocation Cycling and elliptical showed stronger intralimb synergism at the hip and knee than the other two. Based on kinematics, results suggest that elliptical training may have greater transfer to overground walking than cycling and cycling may be more useful for enhancing reciprocal coordination. Further evaluation of these devices in neurological gait disorders is needed., (Published by Elsevier B.V.)

Background: Patients have high reinjury rates after ACL reconstruction. Small knee flexion angles and large peak posterior ground reaction forces in landing tasks increase ACL loading., Questions/purposes: We determined the effects of a knee extension constraint brace on knee flexion angle, peak posterior ground reaction force, and movement speed in functional activities of patients after ACL reconstruction., Patients and Methods: Six male and six female patients 3.5 to 6.5 months after ACL reconstruction participated in the study. Three-dimensional videographic and force plate data were collected while patients performed level walking, jogging, and stair descent wearing a knee extension constraint brace, wearing a nonconstraint brace, and not wearing a knee brace. Knee flexion angle at initial foot contact with the ground, peak posterior ground reaction force, and movement speed were compared across brace conditions and between genders., Results: Wearing the knee extension constraint brace increased the knee flexion angle at initial foot contact for each activity when compared with the other two brace conditions. Wearing the knee extension constraint brace also decreased peak posterior ground reaction force during walking but not during jogging and stair descent., Conclusions: Although the knee extension constraint brace did not consistently reduce the peak posterior ground reaction force in all functional activities, it consistently increased knee flexion angle and should reduce ACL loading as suggested by previous studies. These results suggest the knee extension constraint brace has potential as a rehabilitation tool to alter lower extremity movement patterns of patients after ACL reconstruction to address high reinjury rates.

The most common functional motor goal of lower extremity rehabilitation is to improve walking ability. For reasons of feasibility, safety or intensity, devices are frequently used to facilitate or augment gait training. The objective of this study was to compare the muscle activity patterns of the rectus femoris and semitendinosus muscles during four conditions: overground walking, treadmill walking, stationary cycling, and elliptical training. Ten healthy adults (six male, four female; mean age 22.7±2.9 years, range 20-29) participated and surface electromyographic data were recorded. Linear envelope curves were generated and time normalized from 0 to 100% cycle. The mean plus three standard deviations from a static trial was used as the threshold for muscle activity. Repeated measures analysis of variance procedures were used to detect differences between conditions. Elliptical training demonstrated greater rectus femoris activity and greater rectus femoris/semitendinosus coactivation than all other conditions. Consistent with previous work, treadmill walking demonstrated greater rectus femoris activity than overground walking. Minimal differences in semitendinosus activation were observed between conditions, limited to lower peak activity during cycling compared to treadmill walking. These results provide normative values for rectus femoris and semitendinosus activation for different locomotor training methods and may assist in selecting the most appropriate training device for specific patients. Clinicians and researchers should also consider the kinematic and kinetic differences between tasks, which cannot necessarily be inferred from muscle activation patterns., (Copyright © 2010. Published by Elsevier B.V.)

Nanotechnology has the potential to revolutionise our futures, but has also prompted concerns about the possibility that nanomaterials may harm humans or the biosphere. The unique properties of nanoparticles, that give them novel size dependent functionalities, may also have the potential to cause harm. Discrepancies in existing human health and environmental studies have shown the importance of good quality, well-characterized reference nanomaterials for toxicological studies.Here we make a case for the importance of the detailed characterization of nanoparticles, using several methods, particularly to allow the recognition of impurities and the presence of chemically identical but structurally distinct phases. Methods to characterise fully, commercially available multi-wall carbon nanotubes at different scales, are presented.

The structure of a new mineral jadarite, LiNaSiB(3)O(7)(OH) (IMA mineral 2006-36), has been determined by simulated annealing and Rietveld refinement of laboratory X-ray powder diffraction data. The structure contains a layer of corner-sharing, tetrahedrally coordinated Li, Si and B forming an unbranched vierer single layer, which is decorated with triangular BO(3) groups. The Na ion is situated between the tetrahedral layers in a distorted octahedral site. As the very high boron content in this mineral makes obtaining neutron diffraction data very problematic, ab initio optimization using VASP was used to validate the structure and to better localize the H atom. The H atom is located on the apex of the triangular BO(3) group and is involved in a weak intralayer hydrogen bond. The final Rietveld refinement agrees with the ab initio optimization with regard to a hydrogen bond between the H atom and one of the tetrahedral corner O atoms. The refined structure seems to be of a remarkably high quality given the complexity of the structure, the high proportion of very light elements and the fact that it was determined from relatively low-resolution laboratory data over a limited 2theta range (10-90 degrees 2theta).

Fetal and neonatal ovine plasma protein and lactate dehydrogenase concentrations have been measured between 124 and 146 days gestation in th chronically catheterized fetal sheep and in the newborn lamb. Fetal plasma protein concentration ranged from 24.7 to 77.0 mg . ml-1 and increased at a rate of 1.65 mg . ml-1 . day-1. In contrast, in the first 10 days of neonatal life plasma protein concentration fell steadilyu at a rate of 2.64 mg . ml-1 . day-1. Fetal plasma lactate dehydrogenase concentration increased at a rate of 0.014 IU . ml-1 . day-1 during the period of study. The increase correlated significantly with the rise of fetal plasma protein concentration. In contrast, in the newborn lamb no significant change in plasma lactate dehydrogenase concentration was observed during ther first 10 days after birth.

Intramolecular coupling of active sites in the pyruvate dehydrogenase multienzyme complexes of Escherichia coli, ox heart and Bacillus stearothermophilus was measured at various temperatures. As the temperature was raised, the extent of active-site coupling was found to increase, approaching a maximum near the physiological growth temperature of the organism. Under these conditions, a single pyruvate dehydrogenase (lipoamide) dimer appeared able to cause a rapid (20s) reductive acetylation of probably all 24 polypeptide chains in the dihydrolipoamide acetyltransferase core of the enzyme complex from E. coli at 37 degrees C, and of most if not all of the 60 polypeptide chains in the dihydrolipoamide acetyltransferase cores of the enzymes from ox heart and B. stearothermophilus at 37 degrees C and 60 degrees C respectively. Experiments designed to measure the inter-core and intra-core migration of enzyme subunits suggested that, in the bacterial enzymes at least, this was not a major contributor to active-site coupling.

An immunoassay for prostatic acid phosphatase is described in which a high degree of specificity for the prostatic isoenzyme, obtained by the use of monoclonal antibodies, is combined with great sensitivity, made possible by enzyme-amplified measurement of the combination of the isoenzyme with its antibody. The increase in sensitivity thus achieved is of the order of 170 times that of conventional methods of measurement. The advantages of the enzyme-amplified method have been shown to be particularly useful in detecting and monitoring small abnormalities of prostatic acid phosphatase levels in patients with prostatic cancer.

Enzyme-amplified immunoassays have been adapted for electrochemical measurement, using an NAD+/NADH redox cycle coupled to an electrode via the active site of diaphorase. Two amperometric methods are described, the first employs an organic conducting salt electrode, NMP+/TCNQ-; the second a platinum wire with ferricyanide as electron transfer mediator. In an immunoenzymometric assay for human prostatic acid phosphatase the sensitivities of the electrochemical methods were comparable to that achieved with the existing optical technique, but the dynamic range of the electrochemical assays was increased by at least two orders of magnitude. It is proposed that electrochemical enzyme-amplified immunoassays may eventually replace their optical counterparts.

The sensitivity of enzyme immunoassays may be enhanced by the use of enzyme-amplification. This technique uses the enzyme label in the immunoassay to provide a trigger substance for a secondary system that can generate a large quantity of coloured product. Two examples of enzyme amplifiers are described, using either a substrate cycle with phosphorylated hexose sugars, or a redox cycle involving the coenzyme NAD(+). The redox enzyme-amplifier has a detection limit of less than one attomole for the enzyme label, alkaline phosphatase. The limited dynamic range of enzyme-amplified immunoassays may be overcome by kinetic analysis of the colour development in the enzyme-amplifier, to add at least a further order of magnitude to the range of directly measured analyte concentrations in the immunoassay. This is illustrated in an enzyme-amplified immunoassay for human thyroid stimulating hormone. Amperometric measurement of the enzyme-amplifier provides a method to extend the dynamic range still further and compares favourably with the performance of a gamma counter, a luminometer or a fluorimeter.

A method for greatly enhancing the sensitivity of assays employing enzyme labels is described which offers advantages in assays for a wide range of analytes. The principle of the new approach is that the enzyme label gives rise to a catalytic activator for a specific secondary detection system, the activity of which is measured and related back to the amount of label present and thus of the analyte it is being used to determine (C.H. Self, Eur. Pat. Appl. 80303478.4, 15.4.81 exclusively licenced to IQ (Bio) Ltd.). The general principle of enzyme amplification is illustrated by using alkaline phosphatase as the labelling enzyme and nicotinamide adenine dinucleotide phosphate (NADP) as its substrate. The nicotinamide adenine dinucleotide (NAD) formed catalytically activates a strictly NAD specific redox cycle which produces a coloured formazan as the end product. The measured absorbance is at least two orders of magnitude greater than that achieved by conventional methods. The application of this method to immunoassay is demonstrated by a sensitive, rapid and precise assay for human prostatic acid phosphatase (PAP). Some of the many other applications of this methodology are discussed.

Enzyme immunoassays (EIA) are now used for the quantitation of a wide range of clinically important analytes and have, in many cases, replaced radioimmunoassays, though without improving on the sensitivity of the latter technique. We describe a general enzyme-amplification method which can be used to increase both the speed and the sensitivity of EIA. In this method, the enzyme label is used to catalyse the dephosphorylation of nicotinamide adenine dinucleotide phosphate (NADP+); the NAD+ so formed then catalytically activates an NAD+-specific redox cycle, yielding an intensely coloured formazan dye. The application of this new enzyme detection method has made possible an assay for human thyroid-stimulating hormone (TSH) with a sensitivity of 1 X 10(-5) IU/1 and a progesterone assay which takes only 15 min to complete.

A new and rapid enzyme-amplified immunoassay (AELIA) has been developed for the measurement of progesterone in milk. The AELIA system is a non-isotopic method that gives results within 35 minutes. Milk progesterone concentrations measured in 10 cows sampled daily at various stages of the reproductive cycle were very similar to those recorded by a validated radioimmunoassay. The results show that the speed and sensitivity of the AELIA system would make it possible to diagnose pregnancy rapidly at about 24 days after insemination, to predict the onset of behavioural oestrus from decreasing progesterone values during the third week after a preceding oestrus, and to obtain a daily record of milk progesterone levels in animals treated for infertility of ovarian origin.

A simple method was developed for assessing the intramolecular coupling of active sites in the lipoate acetyltransferase (E2) component of the pyruvate dehydrogenase multienzyme complexes from Escherichia coli, Bacillus stearothermophilus and ox heart and pig heart mitochondria. Samples of enzyme complex were prepared in which the pyruvate decarboxylase (E1) component was selectively and partly inhibited by treatment with increasing amounts of a transition-state analogue, thiamin thio-thiazolone pyrophosphate. The fraction of the E2 component acetylated by incubation with [2-14C] pyruvate, in the absence of CoA, was determined for each sample of partly inhibited enzyme and was found in all cases to exceed the fraction of overall complex activity remaining. This indicated the potential for transacetylation reactions among the lipoic acid residues within the E2 core. A graphic presentation of the data allowed comparison of the active-site coupling in the various enzymes, which may differ in their lipoic acid content (one or two residues per E2 chain). It is clear that active-site coupling is a general property of pyruvate dehydrogenase complexes of octahedral and icosahedral symmetries, the large numbers of subunits in each E2 core enhancing the effect.

In this paper we examine the ability of the mammary gland to remove from circulating blood three compounds which differ in their physico-chemical and structural properties. Mammary extraction of progesterone, oestrone sulphate and epidermal growth factor (EGF) is similar at peak lactation in goats, but the proportion of labelled infusate that is transferred into milk is greater for oestrone sulphate and EGF than progesterone which is rapidly metabolised by mammary tissue. The kinetics of transfer of progesterone, oestrone sulphate and EGF from blood into milk show that transcellular processes are involved, and on the basis of earlier hypotheses and new information reported here the results indicate the probable importance of simple and facilitated diffusion pathways for progesterone and oestrone sulphate, and secretory mechanisms for oestrone sulphate and EGF. Although evidence is lacking for a direct effect of hormones in milk on mammary function, their concentration in milk may reflect changes in local regulation of mammary secretion. Considerable practical value is attached to the immunodiagnostic use of milk hormone concentrations to determine ovarian and placental endocrine activity during pregnancy in domestic ruminants.

A method is described for increasing the response of enzyme immunoassays employing alkaline phosphatase as the label initiating 2 sequential catalytic reactions. First, NADP is dephosphorylated to produce NAD, which catalytically activates a specific redox-cycle involving the enzymes alcohol dehydrogenase and diaphorase. During each turn of the cycle 1 molecule of a tetrazolium salt is reduced to an intensely coloured formazan. The method is capable of detecting as little as 0.01 amol alkaline phosphatase, and when applied to an immunoassay for TSH a sensitivity (zero + 2.5 standard deviations) of 0.0013 mIU/l was obtained.

A new method is described that allows the parallel purification of the pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase multienzyme complexes from ox heart without the need for prior isolation of mitochondria. All the assayable activity of the 2-oxo acid dehydrogenase complexes in the disrupted tissue is made soluble by the inclusion of non-ionic detergents such as Triton X-100 or Tween-80 in the buffer used for the initial extraction of the enzyme complexes. The yields of the pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase complexes are many times greater than those obtained by means of previous methods. In terms of specific catalytic activity, banding pattern on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, sedimentation properties and possession of the regulatory phosphokinase bound to the pyruvate dehydrogenase complex, the 2-oxo acid dehydrogenase complexes prepared by the new method closely resemble those described by previous workers. The greatly improved yield of 2-oxo acid dehydrogenase complexes occasioned by the use of Triton X-100 or Tween-80 as solubilizing agent supports the possibility that the bulk of the pyruvate dehydrogenase complex is associated in some way with the mitochondrial inner membrane and is not free in the mitochondrial matrix space.