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Wearable cuffless photoplethysmographic blood pressure monitors have garnered widespread attention in recent years; however, the long-term performance values of these devices are questionable. Most cuffless blood pressure monitors require initial baseline calibration and regular recalibrations with a cuffed blood pressure monitor to ensure accurate blood pressure estimation, and their estimation accuracy may vary over time if left uncalibrated. Therefore, this study assessed the accuracy and long-term performance of an upper-arm, cuffless photoplethysmographic blood pressure monitor according to the ISO 81060-2 standard. This device was based on a nonlinear machine-learning model architecture with a fine-tuning optimized method. The blood pressure measurement protocol followed a validation procedure according to the standard, with an additional four weekly blood pressure measurements over a 1-month period, to assess the long-term performance values of the upper-arm, cuffless photoplethysmographic blood pressure monitor. The results showed that the photoplethysmographic signals obtained from the upper arm had better qualities when compared with those measured from the wrist. When compared with the cuffed blood pressure monitor, the means ± standard deviations of the difference in BP at week 1 (baseline) were −1.36 ± 7.24 and −2.11 ± 5.71 mmHg for systolic and diastolic blood pressure, respectively, which met the first criterion of ≤5 ± ≤8.0 mmHg and met the second criterion of a systolic blood pressure ≤ 6.89 mmHg and a diastolic blood pressure ≤ 6.84 mmHg. The differences in the uncalibrated blood pressure values between the test and reference blood pressure monitors measured from week 2 to week 5 remained stable and met both criteria 1 and 2 of the ISO 81060-2 standard. The upper-arm, cuffless photoplethysmographic blood pressure monitor in this study generated high-quality photoplethysmographic signals with satisfactory accuracy at both initial calibration and 1-month follow-ups. This device could be a convenient and practical tool to continuously measure blood pressure over long periods of time.

A 58-year-old man developed progressive walking difficulty over 10 years. He had normal development and an unremarkable birth history. At age 30, he developed bilateral drooping eyelids with double vision. At age 48, he developed progressive gait unsteadiness, slurred speech, and swallowing difficulty. At age 55, he needed to walk with a cane. He did not have seizures, hearing loss, or memory impairment. He did not have any history of alcohol abuse or exposures to anticonvulsants. His mother has congenital cardiac disease and diabetes mellitus, and his sister has had epilepsy since childhood. His daughter is healthy.

Background Dystonia is a common feature in spinocerebellar ataxias (SCAs). Whether the presence of dystonia is associated with different rate of ataxia progression is not known. Objectives To study clinical characteristics and ataxia progression in SCAs with and without dystonia. Methods We studied 334 participants with SCA 1, 2, 3 and 6 from the Clinical Research Consortium for Spinocerebellar Ataxias (CRC-SCA) and compared the clinical characteristics of SCAs with and without dystonia. We repeatedly measured ataxia progression by the Scale for Assessment and Rating of Ataxia every 6 months for 2 years. Regression models were employed to study the association between dystonia and ataxia progression after adjusting for age, sex and pathological CAG repeats. We used logistic regression to analyze the impact of different repeat expansion genes on dystonia in SCAs. Results Dystonia was most commonly observed in SCA3, followed by SCA2, SCA1, and SCA6. Dystonia was associated with longer CAG repeats in SCA3. The CAG repeat number in TBP normal alleles appeared to modify the presence of dystonia in SCA1. The presence of dystonia was associated with higher SARA scores in SCA1, 2, and 3. Although relatively rare in SCA6, the presence of dystonia was associated with slower progression of ataxia. Conclusions The presence of dystonia is associated with greater severity of ataxia in SCA1, 2, and 3, but predictive of a slower progression in SCA6. Complex genetic interactions among repeat expansion genes can lead to diverse clinical symptoms and progression in SCAs.

Rationale Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disease that is associated with cell-surface NMDAR-targeting autoantibodies. Typical anti-NMDAR encephalitis symptoms include psychosis, seizure and extrapyramidal side effects. However, early diagnosis of anti-NMDAR encephalitis remains challenging due to the complexity of the motor phenomenon. Patient concerns Here, we report a new diagnosis of anti-NMDAR encephalitis in a young woman with a history of epilepsy. Diagnoses Electroencephalography revealed a typical "extreme delta brush" pattern, which indicated anti-NMDAR encephalitis. Interventions The clinical status of the patient markedly improved after immediate and aggressive immunosuppression therapies. Outcomes The patient was discharged with mild cognitive impairment. However, this was completely resolved 1 month postdischarge. Lessons We conclude that subacute onset focal seizure with psychosis as well as compatible electroencephalography findings (i.e., extreme delta brush patterns) should be considered notable early indicators of anti-NMDAR encephalitis. This would ensure early and effective clinical interventions, which are essential for favorable outcomes.

Background β-Thalassemia major patients with higher total drug levels [deferasirox (DEFR) plus its iron complex] do not yield better serum ferritin (SF) control. This study aimed to determine the concentrations of DEFR and its iron complex (Fe-[DEFR]2) in thalassemia patients to predict the chelation efficacy in terms of SF and cardiac T2* values. Methods Patients' steady-state drug levels at trough (Ctrough) and 2 hours postdose (C2h) were determined. Because iron deposition may cause changes in the hepatic metabolism of amino acids, the concentrations of 40 amino acids in plasma were also assayed at 2 hours postdose. Results A total of 28 patients either dosing daily or twice daily were recruited. After a 1-month DEFR maintenance therapy, 38.8% and 30% of patients from groups of once-daily and twice-daily, respectively, had a plasma DEFR-iron complex formation ratio higher than 0.05 [High Chelation Ratio, (HCR)]. After a 6-month follow-up, those patients who had a HCR (n = 10) at C2h showed more favorable median changes in SF and cardiac T2* values (-388.0, +10.1) than those with a low DEFR-iron complex formation ratio (Low Chelation Ratio; n = 18; +10.5; +4.5) compared with the baseline. The levels of plasma L-arginine, L-alanine, L-glycine, L-norleucine, and L-serine were significantly lower in patients with the low Chelation Ratio condition than the levels in HCR patients. Conclusions This therapeutic drug monitoring study revealed that a DEFR-iron complex formation ratio at C2h might be an applicable indicator of the efficacy of long-term DEFR iron chelation therapy. A better iron-control response to DEFR was observed in the patients with HCRs. The trends for the ratio might have value in dose-setting and need to be validated in a larger cohort.

The passive stiffness at the MCP joint is a result of the elasticity of muscle-tendon units (MTUs) and capsule ligament complex (CLC), however, the relative contributions of these two components are unknown. We hypothesize that the MTUs provide the majority of the contributions to the joint stiffness by generating resistive forces when the MCP joint is flexed or extended. We used the work done by passive moments as a measure for the determination of the contributions to the joint stiffness. We conducted experiments with ten human subjects and collected joint angle and finger tip force data. The total passive moment and joint angle data were fitted with a double exponential model, and the passive moments due to the MTUs were determined by developing subject-specific models of the passive force–length change relationships. Our results show that for all the subjects, the work done by the passive moments from the MTUs is less than 50% of the total work done, and the CLC provides dominant contributions to the joint stiffness throughout the flexion-extension range of the joint angle. Therefore, the hypothesis that the MTUs provide the majority of the contributions to the MCP joint stiffness is not supported. We also determined that the majority of the MTUs passive moment was generated by the extrinsic MTUs and the contributions of the intrinsic MTUs was negligible.

Summary Reasons for performing study: Differences in racing times have been noted on synthetic track surfaces that appear to depend on the temperature of the track. No published study to date has considered this effect in a systematic manner. Objectives: To investigate the relationship between temperature of track and speed of horses racing on a synthetic surface. Potential changes in the wax component of the synthetic track were investigated as one possible cause of changes in the track speed at the temperatures observed. Methods: At Del Mar racetrack (California, USA), the air, surface and subsurface temperatures at 4 depths in the synthetic race surface were measured periodically throughout the day over a 42 day period. The 6 furlong (1.2 km) race (afternoon) and fast training ‘work’ (morning) times were also compiled. Samples of the track were obtained and the wax separated using a solvent separation technique. Differential scanning calorimetry was used to determine the range of temperatures at which the wax from the track underwent softening and other material changes. Transformation temperatures were compared to temperatures acquired from the track to evaluate the likelihood of changes in the wax properties during racing. Results: Average air, surface and subsurface temperatures changed significantly throughout the day. Temperatures were higher during the afternoon race sessions and race times were significantly slower compared to morning work times. Temperatures at which some of the components of the wax began to soften were found to be within the range of temperature measured during track operation. Conclusions: A correlation was found between temperature of the synthetic track and speed of horse. Wax separated from the track showed that the temperatures experienced in the surface during normal operation exceed the temperatures at which the wax begins to experience thermal transformation. It is therefore hypothesised that the wax may be a cause of the observed changes in the track performance. Potential relevance: Future work should include a study of components of the synthetic track responsible for the change and epidemiological association of risk of injury.

Robotic hands are typically too rigid to react against unexpected impacts and disturbances in order to prevent damage. Human hands have great versatility and robustness due, in part, to the passive compliance at the hand joints. In this paper, we present a novel design for joint with passive compliance that is inspired by biomechanical properties of the human hands. The design consists of a compliant material and a set of pulleys that rotate and stretch the material as the joint rotates. We created six different compliant materials, and we optimized the joint design to match the desired humanlike compliance. We present two design features that allow for the tuning of the joint torque profile, namely, a pretension mechanism to increase pretension of the compliant material, and a design of varying pulley configuration. We built a prototype for the new joint by using additive manufacturing to fabricate the design components and built a test-bed with a force sensor and a servo motor. Experimental results show that the joint exhibits a nonlinear, double exponential joint compliance with all six compliant materials. The design feature involving variable pulley configurations is effective in adjusting the slope of joint torque during the joint rotation while the pretension mechanism showed only a limited effect on increasing the torque amplitude. Overall, with its small size, light weight, low friction, and humanlike joint compliance, the presented joint design is ready for implementation in robotic hands.

Passive properties of the human hands, defined by the joint stiffness and damping, play an important role in hand biomechanics and neuromuscular control. Introduction of mechanical element that generates humanlike passive properties in a robotic form may lead to improved grasping and manipulation abilities of the next generation of robotic hands. This paper presents a novel mechanism, which is designed to conduct experiments with the human subjects in order to develop mathematical models of the passive properties at the metacarpophalangeal (MCP) joint. We designed a motor-driven system that integrates with a noninvasive and infrared motion capture system, and can control and record the MCP joint angle, angular velocity, and passive forces of the MCP joint in the index finger. A total of 19 subjects participated in the experiments. The modular and adjustable design was suitable for variant sizes of the human hands. Sample results of the viscoelastic moment, hysteresis loop, and complex module are presented in the paper. We also carried out an error analysis and a statistical test to validate the reliability and repeatability of the mechanism. The results show that the mechanism can precisely collect kinematic and kinetic data during static and dynamic tests, thus allowing us to further understand the insights of passive properties of the human hand joints. The viscoelastic behavior of the MCP joint showed a nonlinear dependency on the frequency. It implies that the elastic and viscous component of the hand joint coordinate to adapt to the external loading based on the applied frequency. The findings derived from the experiments with the mechanism can provide important guidelines for design of humanlike compliance of the robotic hands.

While human-like series passive compliance has been used in previous robotic hand designs, little attention has been paid to parallel passive compliance due to the lack of understanding of its importance in grasping and manipulation. In this paper, we present a novel design of compliant finger inspired by biomechanical features and functionality of human hands. We develop a human-like compact joint by optimizing the geometry of a compliant material and mechanical elements. The joint exhibits a passive double exponential torque matching human-like compliance. We implement the compliant joint into a robotic finger design with human-like tendon routings. We carry out a series of experiments on the finger design with an open-loop control strategy in grasping and manipulation. The results show that the fingers perform reliable grasping and manipulation without feedback. We validate the trajectory tracking with a motion capture system. The human-like compliant fingers follow the desired trajectories with small errors (less than 1 cm). The innovative finger design realizes the human-like hand passive properties and achieves human-like grasping capability.

Purpose Deferasirox (DEFR), when administered BID, improves iron overload and decreases DEFR-related adverse effects in patients with β-thalassemia major. However, the pharmacokinetic (PK) disposition of DEFR and the iron–DEFR complex (Fe-[DEFR] 2 ) in this dosing strategy is unclear. Methods Chromatographic analysis was performed using a solvent delivery system coupled to an HPLC-UV detector to determine the steady-state concentrations of DEFR (C DEFR ) and Fe-(DEFR) 2 (C Fe-[DEFR]2 ) in β-thalassemia major patients (n = 8) following either once-daily or BID dosing, during which the PK parameters of the 2 dosing schedules were compared. Findings An HPLC-UV system for the analysis of blood samples following solid-phase extraction was validated. Patients who received 40 mg/kg of DEFR had higher mean C DEFR and C Fe-[DEFR]2 values at all sampling times. However, concentrations of iron-DEFR complex were similar in patients who received 30 or 40 mg/kg of DEFR in the once-daily group at the 6- to 24-hour sampling times. There was no significant difference in any of the PK parameters; however, DEFR administration BID increased the mean trough levels of DEFR (183.8 [157.5] μmol/L) compared with once daily (87.7 [56.8] μmol/L), whereas all the patients had increased peak levels per individual DEFR dose when they were switched from once daily to BID (139.0 [59.8] μmol/L vs 289.2 [145.8] μmol/L, respectively). Implications Splitting the dose increased the peak levels of DEFR per unit dose in all patients and tends to increase drug exposures, but there were no significant differences in DEFR PK parameter estimates. Switching from once daily to BID may be considered for patients with an inadequate response to chelation therapy to achieve optimal drug levels. Further research is needed with a larger sample size to determine the clinical importance of the significant results due to the interindividual variability of DEFR.

Passive variable stiffness at the human hand joints is shown to be critical for achieving stable and dexterous grasping and manipulation. Our long-term goal is to implement it in robotic hand joints. We introduce a novel design, using linear springs and non-circular cam, for a variable stiffness joint mechanism that mimics the passive stiffness characteristics of human hand joints. We present a methodology based on the principle of virtual work for synthesizing the cam shape in the joint. Key innovations of our design are a) human-like joint stiffness profile, b) large joint range of motion, and c) modular arrangement for varying torque range. We have built a prototype for validating our approach and the experimental results demonstrate that the proposed joint mechanism fulfills the design goals of our study.Copyright © 2013 by ASME

BACKGROUND In this study, the authors studied the effect of thioridazine (TDZ) on the pharmacokinetic profile of quetiapine (QTP) in Taiwanese patients with schizophrenia. METHODS Sixteen subjects with schizophrenia were recruited for this study. The authors pretreated 8 patients with TDZ 50 mg daily continuously given until the end of the study. QTP was administered to all the participants, and their doses were escalated to 300 mg once daily over a 7-day period and maintained for another week. On day 15, blood samples were collected at 12 time points within an 8-hour interval. The authors assayed the plasma levels of QTP with a high-performance liquid chromatography system coupled with ultraviolet detector. RESULTS Significantly decreased plasma levels of QTP after oral administration were observed in patients comedicated with TDZ compared with the QTP monotherapy group at 1.5, 2, and 2.5 hours, and the P values were 0.046, 0.001, and 0.005, respectively. The Cmax of QTP was significantly lower in the group comedicated with TDZ (776.9 ± 175.2 versus 1452.3 ± 707.5 ng/mL; P = 0.002). The oral clearance of QTP was significantly higher in the combined group than in the monothreapy group (123.3 ± 66.8 versus 60.3 ± 28.5 L/h; P = 0.03). Other pharmacokinetic parameters were not significantly different. CONCLUSIONS The coadministration of TDZ significantly decreased plasma QTP level and significantly increased the oral clearance of QTP. Although TDZ is switched to QTP, choosing larger doses of QTP for titration may be necessary to avoid the emergence of psychotic symptoms among schizophrenic patients.

Our long term goal is to develop a new generation of robotic-prosthetic hands that will incorporate key anatomical features of the human hand, especially, the passive dynamics defined by the joint stifftness and damping properties. This paper presents a design of a mechanism that can measure the passive moment of the human hand joint. We designed a motor-driven system, integrating a noninvasive and infrared motion capture system, that can control and record the angle, angular velocity and passive forces of the metacarpophalangeal (MCP) joint in the index finger. A total of 19 subjects participated in the experiments. We conducted two experiments to estimate the total passive moments of the MCP joint from the human subjects. The results showed that the novel design of the mechanism collected the precise passive moments and kinematic data, thus allowing us to develop a comprehensive understanding of the passive properties of the human hand joints. Copyright © 2011 by ASME

The passive joint behavior in the human hand is the result of passive properties of the muscle-tendon units (MTUs) and the elasticity of the soft tissues across the joint. The purpose of the study was to investigate the relative contribution of the MTUs to the net passive torque of the index finger metacarpophalangeal (MCP) joint in flexion and extension. We developed mathematical models to explicitly determine the passive contributions of the seven MTUs to the MCP joint torque. We then compared the computed MTU passive torque to the net passive torque derived from data collected from human subjects. The results show that the MTU properties did not produce the greatest contribution to the the total passive joint torque, especially, at the extremities of the range of motion are dues to factors such as the soft joint tissues. Also, the extrinsic MTUs produced much higher passive joint torques compared to the intrinsic MTUs, and the intrinsic MTUs presented small counterbalance to the net MTU torque in extension. The revelation that most of the net passive joint torque is due to the joint tissue and not due to the MTU elasticity is important for understanding the human hand controls, and also for designing the next generation of robotic hands.