We have previously hypothesized a biological pathway of activity-dependent synaptic plasticity proteins that addresses the dual genetic and environmental contributions to schizophrenia. Accordingly, variations in the immediate early gene EGR3, and its target ARC, should influence schizophrenia susceptibility. We used a pooled Next-Generation Sequencing approach to identify variants across these genes in U.S. populations of European (EU) and African (AA) descent. Three EGR3 and one ARC SNP were selected and genotyped for validation, and three SNPs were tested for association in a replication cohort. In the EU group of 386 schizophrenia cases and 150 controls EGR3 SNP rs1877670 and ARC SNP rs35900184 showed significant associations (p = 0.0078 and p = 0.0275, respectively). In the AA group of 185 cases and 50 controls, only the ARC SNP revealed significant association (p = 0.0448). The ARC SNP did not show association in the Han Chinese (CH) population. However, combining the EU, AA, and CH groups revealed a highly significant association of ARC SNP rs35900184 (p = 2.353 x 10−7; OR [95% CI] = 1.54 [1.310–1.820]). These findings support previously reported associations between EGR3 and schizophrenia. Moreover, this is the first report associating an ARC SNP with schizophrenia and supports recent large-scale GWAS findings implicating the ARC complex in schizophrenia risk. These results support the need for further investigation of the proposed pathway of environmentally responsive, synaptic plasticity-related, schizophrenia genes.
INTRODUCTION Abnormal tibial torsion is a common pediatric problem, and there are many existing measurement methods. The purpose of this study was to compare three methods of measuring tibial torsion for its evaluation: computed tomography, physical examination, and motion capture. MATERIALS AND METHODS Twenty healthy children and 20 children with myelomeningocele underwent measures of tibial torsion bilaterally. Measurements were compared using correlation and Bland-Altman plots of the difference between measurements. RESULTS All three measurements were moderately correlated in controls (r≥0.49, p≤0.002) and in patients (r≥0.51, p≤0.001). In controls, the motion capture measurements were on average 2° more lateral than the clinical measurements whereas motion capture and clinical measurements were 13° and 15° more medial than CT measurements, respectively. Similarly for patients, motion capture measurements were on average 5° more medial than clinical measurements, and motion capture and clinical measurements were 26° and 22° more medial than CT measurements. CONCLUSIONS The approximate 20° difference between the clinical or motion capture measures and the CT measure suggests that clinical evaluation identifies different axes than those defined based on skeletal anatomy. Clinical or motion capture methods may be used in lieu of imaging methods for measuring tibial torsion with the knowledge that these methods provide less lateral measurements than measurements obtained using CT.
Nonlinear Bayesian filtering of surface electromyography (EMG) can provide a stable output signal with little delay and the ability to change rapidly, making it a potential control input for prosthetic or communication devices. We hypothesized that myocontrol follows Fitts' Law, and that Bayesian filtered EMG would improve movement times and success rates when compared with linearly filtered EMG. We tested the two filters using a Fitts' Law speed-accuracy paradigm in a one-muscle myocontrol task with EMG captured from the dominant first dorsal interosseous muscle. Cursor position in one dimension was proportional to EMG. Six indices of difficulty were tested, varying the target size and distance. We examined two performance measures: movement time (MT) and success rate. The filter had a significant effect on both MT and success. MT followed Fitts' Law and the speed-accuracy relationship exhibited a significantly higher channel capacity when using the Bayesian filter. Subjects seemed to be less cautious using the Bayesian filter due to its lower error rate and smoother control. These findings suggest that Bayesian filtering may be a useful component for myoelectrically controlled prosthetics or communication devices. NEW & NOTEWORTHY Whereas previous work has focused on assessing the Bayesian algorithm as a signal processing algorithm for EMG, this study assesses the use of the Bayesian algorithm for online EMG control. In other words, the subjects see the output of the filter and can adapt their own behavior to use the filter optimally as a tool. This study compares how subjects adapt EMG behavior using the Bayesian algorithm vs. a linear algorithm.
The design of myocontrolled devices faces particular challenges in children with dyskinetic cerebral palsy because the electromyographic signal for control contains both voluntary and involuntary components. We hypothesized that voluntary and involuntary components of movements would be uncorrelated and thus detectable as different synergistic patterns of muscle activity, and that removal of the involuntary components would improve online EMG-based control. Therefore, we performed a synergy-based decomposition of EMG-guided movements, and evaluated which components were most controllable using a Fitts’ Law task. Similarly, we also tested which muscles were most controllable. We then tested whether removing the uncontrollable components or muscles improved overall function in terms of movement time, success rate, and throughput. We found that removal of less controllable components or muscles did not improve EMG control performance, and in many cases worsened performance. These results suggest that abnormal movement in dyskinetic CP is consistent with a pervasive distortion of voluntary movement rather than a superposition of separable voluntary and involuntary components of movement.
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