Experimental demonstration of an actuated exercise machine.

Experimental results are obtained for a single degree of freedom prototype next generation exercise machine that aims to maximize the user's power output and ensure passivity with the user. In an effort to optimize the user's power expenditure, the desired velocity trajectory is developed that seeks the unknown user-dependent optimal velocity setpoint. A numerical extremum-seeking algorithm is utilized to seek the optimal velocity setpoint while ensuring the trajectory is sufficiently differentiable. To track the reference trajectory and to ensure passivity, a nonlinear controller is utilized.

Repetitive learning control: a Lyapunov-based approach.

In this paper, a learning-based feedforward term is developed to solve a general control problem in the presence of unknown nonlinear dynamics with a known period. Since the learning-based feedforward term is generated from a straightforward Lyapunov-like stability analysis, the control designer can utilize other Lyapunov-based design techniques to develop hybrid control schemes that utilize learning-based feedforward terms to compensate for periodic dynamics and other Lyapunov-based approaches (e.g., adaptive-based feedforward terms) to compensate for nonperiodic dynamics. To illustrate this point, a hybrid adaptive/learning control scheme is utilized to achieve global asymptotic link position tracking for a robot manipulator.

Adaptive tracking control of a wheeled mobile robot via an uncalibrated camera system.

This paper considers the problem of position/orientation tracking control of wheeled mobile robots via visual servoing in the presence of parametric uncertainty associated with the mechanical dynamics and the camera system. Specifically, we design an adaptive controller that compensates for uncertain camera and mechanical parameters and ensures global asymptotic position/orientation tracking. Simulation and experimental results are included to illustrate the performance of the control law.

Global exponential tracking control of a mobile robot system via a PE condition.

This paper presents the design of a differentiable, kinematic control law that achieves global asymptotic tracking. In addition, we also illustrate how the proposed kinematic controller provides global exponential tracking provided the reference trajectory satisfies a mild persistency of excitation (PE) condition. We also illustrate how the proposed kinematic controller can be slightly modified to provide for global asymptotic regulation of both the position and orientation of the mobile robot. Finally, we embed the differentiable kinematic controller inside of an adaptive controller that fosters global asymptotic tracking despite parametric uncertainty associated with the dynamic model. Experimental results are also provided to illustrate the performance of the proposed adaptive tracking controller.

Treatment of progressive multiple sclerosis with pulse cyclophosphamide/methylprednisolone: response to therapy is linked to the duration of progressive disease.

OBJECTIVE: To determine if there are variables linked to responsiveness to pulse cyclophosphamide/methylprednisolone therapy in progressive Multiple Sclerosis (MS). BACKGROUND: MS is a presumed autoimmune disease of the CNS in which immunosuppressive and immunomodulatory treatments are being used. We have treated patients with the progressive form of MS using a regimen consisting of pulse cyclophosphamide/methylprednisolone that is given as an outpatient at 4 - 8 week intervals similar to lupus nephritis protocols. DESIGN/METHODS: We investigated a series of 95 consecutive progressive MS patients treated in an open label fashion in an effort to identify factors linked to response to treatment. Clinical outcome measures included status at 12 months and time to failure determined by EDSS change and global physician impression. For each endpoint, associations were examined between outcome and patient characteristics including gender, age at onset of disease and treatment, EDSS 1 year previously and at start of treatment, duration of MS, previous treatment, age at onset and duration of progression, and primary vs secondary progressive MS. RESULTS: Of the variables studied, age, gender, age at onset, and age at treatment did not correlate with response to therapy. The most significant variable that correlated with response was length of time the patient was in the progressive phase (P=0.048, 12 month change in EDSS; P=0.017, risk for time to failure). Patients that improved on therapy at 12 months had progressive disease for an average of 2.1 years prior to treatment, whereas those stable or worse had progressive disease for 5.0 and 4.1 years respectively. There was a trend (P=0.08) favoring positive clinical responses in secondary progressive as opposed to primary progressive patients. CONCLUSIONS: Our data suggest that progressive MS may become refractory to immunosuppressive therapy with time and early intervention when patients enter the progressive stage should be considered. Furthermore, in trials of immunosuppressive agents for progressive MS, duration of progression should be considered as a randomization and analysis variable.

Multiple neural-network-based adaptive controller using orthonormal activation function neural networks.

A direct adaptive control scheme is developed using orthonormal activation function-based neural networks (OAFNN's) for trajectory tracking control of a class of nonlinear systems. Multiple OAFNN's are employed in these controllers for feedforward compensation of unknown system dynamics. Choice of multiple OAFNN's allows a reduction in overall network size reducing the computational requirements. The network weights are tuned on-line, in real time. The overall stability of the system and the neural networks is guaranteed using Lyapunov analysis. The developed neural controllers are evaluated experimentally and the experimental results are shown to support theoretical analysis. The effects of network parameters on system performance are experimentally evaluated and are presented in this research. The superior learning capability of OAFNN's is demonstrated through experimental results. The OAFNN's were able to model the true nature of the nonlinear system dynamics characteristics for a rolling-sliding contact as well as for stiction.

Modified Kidner procedure utilizing a Mitek bone anchor.

The recent development of small bone suture anchors has created several potential applications in reconstructive surgery of the foot. Mitek bone anchors are simple to insert, require less aggressive dissection and surgical time than reefing of the redundant posterior tibial tendon, and are a reliable method of tendon-to-bone fixation. Mitek bone anchors are an excellent technique for the treatment of redundant tibialis posterior tendon following a modified Kidner procedure. In modified Kidner procedures involving an excessively large os tibiale externum, Mitek anchoring of the redundant tibialis posterior tendon to the navicular bone is an excellent means for secure plication of the posterior tibial tendon in cases involving intraoperative tendon laxity. A description of the Mitek Anchor System and technique of application in a modified Kinder procedure is presented. The purpose of this study was to describe patient satisfaction and long-term clinical outcomes of the modified Kinder procedure with and without the Mitek bone anchoring system. A retrospective study of the modified Kinder procedure was performed with 13 patients being evaluated, seven with Mitek anchoring and six without. The University of Maryland 100-point Painful Foot Center Scoring System was modified to be more specific to the modified Kinder procedure for assessment of subjective long-term results. Patient overall satisfaction was rated good to excellent by 85.6% of patients in the Mitek group and by 100% of patients in the non-Mitek group. Use of the Mitek anchor allowed for quicker postoperative recovery to resumption of ambulation without assistive devices (average of 3 weeks vs. 4.42 weeks) and a quicker return to pain-free ambulation in normal shoegear (average of 4 weeks vs. 6 weeks). Mitek anchoring of the tibialis posterior tendon, theoretically, increases medial arch support as evidenced by 14% of the Mitek group and 67% of the non-Mitek group requiring postoperative orthotics.

Altered expression of RET proto-oncogene product in prostatic intraepithelial neoplasia and prostate cancer.

BACKGROUND: The RET proto-oncogene encodes a protein that belongs to the tyrosine kinase growth factor receptor family. Germline point mutations in RET are found in individuals with multiple endocrine neoplasia (MEN) syndromes, and gene rearrangements have been reported in papillary thyroid cancers. We recently identified transcripts of the RET proto-oncogene in human prostate cancer xenografts and prostate cancer cell lines by means of reverse transcription-polymerase chain reaction analyses. The purpose of this study was to investigate Ret protein expression in human prostate tissue. METHODS: Ret protein expression was evaluated immunohistochemically in formalin-fixed, paraffin-embedded whole-prostate sections. The prostate specimens were obtained from 30 patients with prostate cancer after radical prostatectomies. Ret protein expression was compared in tumor foci and benign prostatic tissue. Medullary thyroid carcinoma tissue associated with an MEN syndrome and papillary thyroid cancer tissue served as positive controls. RESULTS: Ret appeared to be overexpressed in high-grade (histopathologically advanced) prostatic intraepithelial neoplasia (PIN) and prostate cancer when compared with its expression level in benign prostatic secretory epithelium. In addition, there was an apparent increase in Ret protein expression with decreased cellular differentiation, i.e., increasing Gleason pattern. CONCLUSION: Expression of the RET proto-oncogene in benign prostatic epithelium, high-grade PIN, and histopathologically advanced prostate cancer suggests that RET may play a role in the growth of both benign and neoplastic prostate epithelial cells.

Robust neural-network control of rigid-link electrically driven robots.

A robust neural-network (NN) controller is proposed for the motion control of rigid-link electrically driven (RLED) robots. Two-layer NN's are used to approximate two very complicated nonlinear functions. The main advantage of our approach is that the NN weights are tuned on-line, with no off-line learning phase required. Most importantly, we can guarantee the uniformly ultimately bounded (UUB) stability of tracking errors and NN weights. When compared with standard adaptive robot controllers, we do not require lengthy and tedious preliminary analysis to determine a regression matrix. The controller can be regarded as a universal reusable controller because the same controller can be applied to any type of RLED robots without any modifications.

Fibrin deposition in Peyronie's disease plaque.

PURPOSE: Peyronie's disease is a pathological fibrosis characterized by excessive deposition of collagen in the plaque. Although the etiology of Peyronie's disease is unknown, trauma has been hypothesized as the inciting event. In an effort to obtain more insight into the pathogenesis of Peyronie's disease plaque tissue was examined for collagen, elastic fiber, and fibrin content and distribution. MATERIALS AND METHODS: Plaque tissue specimens from 33 patients with Peyronie's disease, control penile tissue and nodular tissue from 8 patients with Dupuytren's contracture were analyzed histochemically for collagen staining and elastic fiber structure and distribution. Plaque tissue from 19 Peyronie's disease patients, control tissue and nodular tissue from Dupuytren's disease were also analyzed for the presence of fibrin by histochemical staining and immunoblotting. RESULTS: Aberrantly stained collagen was detected in 32 of 33 plaque specimens (97%) and disrupted elastic fibers in 31 of the same specimens (94%). Fibrin deposition was detected histochemically in plaque tissue from 18 of 19 patients (95%) but it was not detectable in normal or scarred tunica from control patients. The presence of authentic fibrin accumulation in plaque tissue was confirmed by immunoblot analysis but fibrin was not detected in dermal tissue extracts from the same patient. Aberrant collagen staining and fibrin deposition were detected in nodular tissue from 7 of 8 Dupuytren's contracture patients (88%) and altered elastic fibers in 5 of the same patients (63%). CONCLUSIONS: Deposition of fibrin in plaque tissue is consistent with the hypothesis that repetitive microvascular injury results in fibrin deposition in the tissue space and has served to provide insights into the pathophysiology of Peyronie's disease. We propose a model that accounts for the clinical and biological features of Peyronie's disease.

Hereditary ataxia with sensory neuronopathy: Biemond's ataxia.

We report the case of a man with late-onset hereditary ataxia and sensory loss. Three of his sisters were affected by a similar disorder; to date no other members of his family have developed symptoms. The clinical features of this family are similar to a rare form of autosomal dominant hereditary ataxia, recently classified as SCA4. Postmortem findings indicate that this syndrome is marked by degeneration of cerebellar Purkinje cells, dorsal root sensory ganglion neurons, and the ascending posterior columns. Similar clinical and pathologic findings were reported by Biemond in 1954.

An adaptive link position tracking controller for rigid-link flexible-joint robots without velocity measurements.

This paper presents an adaptive partial state feedback controller for rigid-link flexible-joint (RLFJ) robots. The controller compensates for parametric uncertainty throughout the entire mechanical system while only requiring measurement of link position and actuator position. To eliminate the need for measuring link velocity and actuator velocity a set of filters is utilized as a surrogate for the unmeasurable quantities. Based on this set of filters, an adaptive integrator backstepping procedure is used to develop a torque input controller which guarantees semiglobal asymptotic link position tracking while also ensuring that all signals remain bounded during closed-loop operation. Simulation results for a two-link RLFJ robot are utilized to validate the performance of the proposed controller.

Adaptive position/force control of robot manipulators without velocity measurements: theory and experimentation.

In this paper, we design an adaptive position/force controller for robot manipulators during constrained motion. The proposed controller can compensate for parametric uncertainty while only requiring measurements of link position and end-effector force. A filtering technique is utilized to produce a pseudo-velocity error signal and thus, eliminate the need for link velocity measurements. The control strategy provides semiglobal asymptotic tracking performance for the end-effector position and the interaction force between the constraint and the end-effector. An experimental implementation of the proposed controller on a two-link planar robot is also presented.

Effectiveness of ranitidine 150 mg at bedtime as maintenance therapy for healed gastric ulcers.

As many as 89% of gastric ulcer patients experience ulcer recurrences within 1 year of successful healing with conventional antiulcer therapies. Because ranitidine is effective in the healing of gastric and duodenal ulcers and the maintenance of healed duodenal ulcers, we hypothesized that ranitidine would also be effective in the maintenance of healed gastric ulcers. A 48-week, placebo-controlled, randomized, double-blind, multicenter trial was conducted to compare ranitidine 150 mg administered at bedtime with placebo for the maintenance of healed gastric ulcers. Endoscopies were performed at baseline and repeated after 12, 24, 36, and 48 weeks of treatment. Gastric ulcer recurrence rates at each scheduled endoscopy were significantly lower in patients receiving ranitidine (5%, 13%, 16%, and 19%, respectively) compared with those receiving placebo (20%, 30%, 40%, and 50%, respectively). Compared with placebo, ranitidine was more effective in maintaining healed gastric ulcers regardless of previous gastric ulcer history, smoking status, age (< 65 vs > or = 65 years), or sex. There were no significant differences between the two treatment groups in the number of patients experiencing adverse events or laboratory abnormalities. Ranitidine 150 mg administered at bedtime provides safe and effective treatment for the maintenance of healed gastric ulcers.

A familial factor independent of CAG repeat length influences age at onset of Machado-Joseph disease.

Machado-Joseph disease (MJD) is a late-onset, progressive, neurodegenerative disorder caused by the expansion of an unstable trinucleotide (CAG) repeat sequence in a novel gene (MJD1) on chromosome 14. Previous studies showed that age at onset is negatively correlated with the number of CAG repeat units, but only part of the variation in onset age is explained by CAG repeat length. Ages at onset and CAG repeat lengths of 136 MJD patients from 23 kindreds of Portuguese descent were analyzed, to determine whether familial factors independent of CAG repeat length modulate age at onset of MJD. Correlation among sibs for onset age adjusted for CAG repeat length was .43, which indicates that an environmental or genetic factor common to sibs influences onset age. Positive correlations were also observed for avuncular (r = .22) and first-cousin pairs (r = .28), which supports the hypothesis that a genetic factor is influencing age at onset. Commingling analysis of onset ages adjusted for CAG repeat length identified three distributions in this population of affected individuals. Further studies of a much larger sample are needed to determine whether these distributions represent the influence of a genetic or environmental factor.

Entrapment neuropathies: clinical overview.

Causes include congenital defects, trauma, and inflammation. Some forms are overdiagnosed, particularly carpal tunnel syndrome. Others--such as thoracic outlet syndrome and anterior interosseous nerve syndrome--are rare. Diagnosis and management are relatively straightforward in most cases, but much remains to be learned about the natural course and prevention of these disorders.

Correlation between CAG repeat length and clinical features in Machado-Joseph disease.

Machado-Joseph disease (MJD) is associated with the expansion of a CAG trinucleotide repeat in a novel gene on 14q32.1. We confirmed the presence of this expansion in 156 MJD patients from 33 families of different geographic origins: 15 Portuguese Azorean, 2 Brazilian, and 16 North American of Portuguese Azorean descent. Normal chromosomes contain between 12 and 37 CAG repeats in the MJD gene, whereas MJD gene carriers have alleles within the expanded range of 62-84 CAG units. The distribution of expanded alleles and the gap between normal and expanded allele sizes is either inconsistent with a premutation hypothesis or most (if not all) of the alleles we studied descend from a common ancestor. There is a strong correlation between the expanded repeat size and the age at onset of the disease as well as the clinical presentation. There is mild instability of the CAG tract length with transmission of the expanded alleles; both increase and decrease in size between parents and progeny occur, with larger variations in male than in female transmissions. Together, these effects can partly explain the variability of age at onset and of phenotypic features in MJD; however, other modifying factors must exist.

Therapy for multiple sclerosis.

Multiple sclerosis is hypothesized to be a cell-mediated autoimmune disease directed against central nervous system myelin. Immunotherapy is directed at decreasing the autoimmune response using both specific and nonspecific modulation of the immune system in an attempt to halt accumulation of disability. Symptomatic therapy may also help multiple sclerosis patients.