Using kinematics to re-define the pull test as a quantitative biomarker of the postural response in normal pressure hydrocephalus patients.

Quantitative biomarkers are needed for the diagnosis, monitoring and therapeutic assessment of postural instability in movement disorder patients. The goal of this study was to create a practical, objective measure of postural instability using kinematic measurements of the pull test. Twenty-one patients with normal pressure hydrocephalus and 20 age-matched control subjects were fitted with inertial measurement units and underwent 10-20 pull tests of varying intensities performed by a trained clinician. Kinematic data were extracted for each pull test and aggregated. Patients participated in 103 sessions for a total of 1555 trials while controls participated in 20 sessions for a total of 299 trials. Patients were separated into groups by MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) pull test score. The center of mass velocity profile easily distinguished between patient groups such that score increases correlated with decreases in peak velocity and later peak velocity onset. All patients except those scored as "3" demonstrated an increase in step length and decrease in reaction time with increasing pull intensity. Groups were distinguished by differences in the relationship of step length to pull intensity (slope) and their overall step length or reaction time regardless of pull intensity (y-intercept). NPH patients scored as "normal" on the MDS-UPDRS scale were kinematically indistinguishable from age-matched control subjects during a standardized perturbation, but could be distinguished from controls by their response to a range of pull intensities. An instrumented, purposefully varied pull test produces kinematic metrics useful for distinguishing clinically meaningful differences within hydrocephalus patients as well as distinguishing these patients from healthy, control subjects.

Cardiac myosin binding protein-C phosphorylation accelerates ß-cardiac myosin detachment rate in mouse myocardium.

Cardiac myosin binding protein-C (cMyBP-C) is a thick filament protein that influences sarcomere stiffness and modulates cardiac contraction-relaxation through its phosphorylation. Phosphorylation of cMyBP-C and ablation of cMyBP-C have been shown to increase the rate of MgADP release in the acto-myosin cross-bridge cycle in the intact sarcomere. The influence of cMyBP-C on Pi-dependent myosin kinetics has not yet been examined. We investigated the effect of cMyBP-C, and its phosphorylation, on myosin kinetics in demembranated papillary muscle strips bearing the ß-cardiac myosin isoform from nontransgenic and homozygous transgenic mice lacking cMyBP-C. We used quick stretch and stochastic length-perturbation analysis to characterize rates of myosin detachment and force development over 0-12 mM Pi and at maximal (pCa 4.8) and near-half maximal (pCa 5.75) Ca2+ activation. Protein kinase A (PKA) treatment was applied to half the strips to probe the effect of cMyBP-C phosphorylation on Pi sensitivity of myosin kinetics. Increasing Pi increased myosin cross-bridge detachment rate similarly for muscles with and without cMyBP-C, although these rates were higher in muscle without cMyBP-C. Treating myocardial strips with PKA accelerated detachment rate when cMyBP-C was present over all Pi, but not when cMyBP-C was absent. The rate of force development increased with Pi in all muscles. However, Pi sensitivity of the rate force development was reduced when cMyBP-C was present versus absent, suggesting that cMyBP-C inhibits Pi-dependent reversal of the power stroke or stabilizes cross-bridge attachment to enhance the probability of completing the power stroke. These results support a functional role for cMyBP-C in slowing myosin detachment rate, possibly through a direct interaction with myosin or by altering strain-dependent myosin detachment via cMyBP-C-dependent stiffness of the thick filament and myofilament lattice. PKA treatment reduces the role for cMyBP-C to slow myosin detachment and thus effectively accelerates ß-myosin detachment in the intact myofilament lattice.NEW & NOTEWORTHY Length perturbation analysis was used to demonstrate that ß-cardiac myosin characteristic rates of detachment and recruitment in the intact myofilament lattice are accelerated by Pi, phosphorylation of cMyBP-C, and the absence of cMyBP-C. The results suggest that cMyBP-C normally slows myosin detachment, including Pi-dependent detachment, and that this inhibition is released with phosphorylation or absence of cMyBP-C.

Physiological system analysis of the kidney by high-temporal-resolution T2∗ monitoring of an oxygenation step response.

PURPOSE: Examine the feasibility of characterizing the regulation of renal oxygenation using high-temporal-resolution monitoring of the T2∗ response to a step-like oxygenation stimulus. METHODS: For T2∗ mapping, multi-echo gradient-echo imaging was used (temporal resolution = 9 seconds). A step-like renal oxygenation challenge was applied involving sequential exposure to hyperoxia (100% O2 ), hypoxia (10% O2 + 90% N2 ), and hyperoxia (100% O2 ). In vivo experiments were performed in healthy rats (N = 10) and in rats with bilateral ischemia-reperfusion injury (N = 4). To assess the step response of renal oxygenation, a second-order exponential model was used (model parameters: amplitude [A], time delay [Δt], damping constant [D], and period of the oscillation [T]) for renal cortex, outer stripe of the outer medulla, inner stripe of the outer medulla, and inner medulla. RESULTS: The second-order exponential model permitted us to model the exponential T2∗ recovery and the superimposed T2∗ oscillation following renal oxygenation stimulus. The in vivo experiments revealed a difference in Douter medulla between healthy controls (D < 1, indicating oscillatory recovery) and ischemia-reperfusion injury (D > 1, reflecting aperiodic recovery). The increase in Douter medulla by a factor of 3.7 (outer stripe of the outer medulla) and 10.0 (inner stripe of the outer medulla) suggests that this parameter might be rather sensitive to (patho)physiological oxygenation changes. CONCLUSION: This study demonstrates the feasibility of monitoring the dynamic oxygenation response of renal tissues to a step-like oxygenation challenge using high-temporal-resolution T2∗ mapping. Our results suggest that the implemented system analysis approach may help to unlock questions regarding regulation of renal oxygenation, with the ultimate goal of providing imaging means for diagnostics and therapy of renal diseases.

Characteristics of First Recovery Step Response following Unexpected Loss of Balance during Walking: A Dynamic Approach.

INTRODUCTION: Many falls in older adults occur during walking and result in lateral falls. The ability to perform a recovery step after balance perturbation determines whether a fall will occur. AIM: To investigate age-related changes in first recovery step kinematics and kinematic adaptations over a wide range of lateral perturbation magnitudes while walking. METHODS: Thirty-five old (78.5 ± 5 years) and 19 young adults (26.0 ± 0.8 years) walked at their preferred walking speed on a treadmill. While walking, the subjects were exposed to announced right/left perturbations in different phases of the gait cycle that were gradually increased in order to trigger a recovery stepping response. The subjects were instructed to react naturally and try to avoid falling. Kinematic analysis was performed to analyze the first recovery step parameters (e.g., step initiation, swing duration, step length, and the estimated distance of the center of mass from the base of support [dBoS]). RESULTS: Compared with younger adults, older adults displayed a significantly lower step threshold and at lower perturbation magnitudes during the experiment. Also, they showed slower compensatory step initiation, shorter step length, and dBoS with similar step recovery times. As the perturbation magnitudes increased, older adults showed very small, yet significant, decreases in the timing of the step response, and increased their step length. Younger adults did not show changes in the timing of stepping, with a tendency toward a significant increase in step length. CONCLUSIONS: First compensatory step performance is impaired in older adults. In terms of the dynamic approach, older adults were more flexible, i.e., less automatic, while younger adults displayed more automatic behavior.

The basic mechanical structure of the skeletal muscle machinery: One model for linking microscopic and macroscopic scales.

Measuring, analysing, and modelling muscle contraction has a long history. In consequence, some signature characteristics of skeletal muscle contraction have been found. On a microscopic level, these are the typical non-steady-state responses of the cross-bridge bindings to steps in force and length. On a macroscopic level, the force-velocity, enthalpy-velocity, and efficiency-velocity relations for concentric steady-state contractions are crucial characteristics. As these characteristics were repeatedly confirmed across animal species and sizes, they are expected to pinpoint basic physical properties of the mechanical structure that embodies the skeletal muscle machinery. The approach presented in this article explains, for the first time, these characteristics at both the microscopic and the macroscopic scale with one model and one set of parameters. According to expectation, this model is solely built on the basic mechanical structure of the muscular, contractile machinery. Its four mechanical elements represent the source of work, the serial elasticity, damping due to mechanical deformation, and damping due to the biochemical ATP hydrolysis in the energy conversion process. For explaining all mentioned non-steady-state and steady-state characteristics at once, the model requires, at maximum, ten parameters of which only three parameters representing damping properties plus one representing muscle-internal steady-state kinematics were free to be chosen. All other parameters were already fixed by literature knowledge of the geometrical structure and force characteristics of one cross-bridge. Amongst other results, we found that (i) the most reduced variant of the model is mathematically equivalent to a former version and (ii) the curvature parameter of the Hill relation can be interpreted as the ratio of strengths of the two modelled damping processes. This model approach not only unifies microscopic and macroscopic experimental findings, but further allows to interpret findings of molecular damping and elasticity and scaling of muscle properties, as discussed in this article.

Computational Experiments on the Step and Frequency Responses of a Three-Axis Thermal Accelerometer.

The sensor response has been reported to become highly nonlinear when the acceleration added to a thermal accelerator is very large, so the same response can be observed for two accelerations with different magnitudes and opposite signs. Some papers have reported the frequency response for the horizontal acceleration to be a first-order system, while others have reported it to be a second-order system. The response for the vertical acceleration has not been studied. In this study, computational experiments were performed to examine the step and frequency responses of a three-axis thermal accelerometer. The results showed that monitoring the temperatures at two positions and making use of cross-axis sensitivity allow a unique acceleration to be determined even when the range of the vertical acceleration is very large (e.g., -10,000-10,000 g). The frequency response was proven to be a second-order system for horizontal acceleration and a third-order system for vertical acceleration.

Step Response Characteristics of Polymer/Ceramic Pressure-Sensitive Paint.

Experiments and numerical simulations have been used in this work to understand the step response characteristics of Polymer/Ceramic Pressure-Sensitive Paint (PC-PSP). A recently developed analytical model describing the essential physics in PC-PSP quenching kinetics is used, which includes the effect of both diffusion time scale and luminescent lifetime on the net response of PC-PSP. Step response simulations using this model enables an understanding of the effects of parameters, such as the diffusion coefficient of O2 in the polymer/ceramic coating, attenuation of excitation light, ambient luminescent lifetime, sensitivity, and the magnitude and direction of pressure change on the observed response time scales of PC-PSP. It was found that higher diffusion coefficient and greater light attenuation lead to faster response, whereas longer ambient lifetime and larger sensitivity lead to slower response characteristics. Due to the inherent non-linearity of the Stern-Volmer equation, response functions also change with magnitude and direction of the pressure change. Experimental results from a shock tube are presented where the effects of varying the roughness, pressure jump magnitude and luminophore probe have been studied. Model parameters have been varied to obtain a good fit to experimental results and this optimized model is then used to obtain the response time for a step decrease in pressure, an estimate of which is currently not obtainable from experiments.

Optimal tuning of PID controllers with derivative filter for stable processes using three points from the step response.

This paper proposes a novel approach for tuning Proportional Integral Derivative (PID) controllers, utilizing experimental data obtained from an open-loop step input. We propose to use the measurements of the times taken to reach 5%, 35.3% and 85.3% of the final output, as well as the process static gain, to tune the controller. The tuning equations are applicable for a wide range of stable and over damped systems. Starting from an approximate model with three real poles and time delay (obtained from the measurements), the tuning equations approximate the controller that minimizes the Integral of Absolute Error (IAE) of the disturbance response. The designer can freely decide the Sensitivity Margin (Ms) to fix a desired robustness, as a difference with respect to other known methods where the user chooses among few predefined robustness values. The user can also select freely the derivative filter parameter, N, to find the required compromise between speed response and measurement noise amplification. For N=0 a PI controller is chosen. As N increases, a faster PID controller is selected, with higher noise amplification. We have also developed a web-based application and an Android application, downloadable for free, that implement the tuning equations as well as the whole required procedure.

The different contributions of the eight prefrontal cortex subregions to reactive responses after unpredictable slip perturbations and vibrotactile cueing.

Introduction: Recent advancements in functional near-infrared spectroscopy technology have offered a portable, wireless, wearable solution to measure the activity of the prefrontal cortex (PFC) in the human neuroscience field. This study is the first to validate the different contributions made by the PFC's eight subregions in healthy young adults to the reactive recovery responses following treadmill-induced unpredictable slip perturbations and vibrotactile cueing (i.e., precues). Methods: Our fall-inducing technology platform equipped with a split-belt treadmill provided unpredictable slip perturbations to healthy young adults while walking at their self-selected walking speed. A portable, wireless, wearable, and multi-channel (48 channels) functional near-infrared spectroscopy system evaluated the activity of PFC's eight subregions [i.e., right and left dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), frontopolar prefrontal cortex (FPFC), and orbitofrontal cortex (OFC)] as quantified by oxyhemoglobin and deoxyhemoglobin concentrations. A motion capture system and two force plates beneath the split-belt treadmill were used to quantify participants' kinematic and kinetic behavior. All participants completed 6 trials: 2 consecutive trials without vibrotactile cueing and with a slip perturbation (control trials); 3 trials with vibrotactile cueing [2 trials with the slip perturbation (cueing trial) and 1 trial without the slip perturbation (catch trial)], and 1 trial without vibrotactile cueing and with a slip perturbation (post-control trial). The PFC subregions' activity and kinematic behavior were assessed during the three periods (i.e., standing, walking, and recovery periods). Results: Compared to the walkers' standing and walking periods, recovery periods showed significantly higher and lower levels of oxyhemoglobin and deoxyhemoglobin concentrations, respectively, in the right and left DLPFC, VLPFC, and FPFC, regardless of the presence of vibrotactile cueing. However, there was no significant difference in the right and left OFC between the three periods. Kinematic analyses confirmed that vibrotactile cueing significantly improved reactive recovery responses without requiring more involvement by the PFC subregions, which suggests that the sum of attentional resources is similar in cued and non-cued motor responses. Discussion: The results could inform the design of wearable technologies that alert their users to the risks of falling and assist with the development of new gait perturbation paradigms that prompt reactive responses.

A new method for experimental tuning of PI controllers based on the step response.

In this paper we present a new method for tuning Proportional Integral (PI) controllers from experimental data obtained through an open loop step test over the process to be controlled. The tuning procedure requires first the measurement of the process gain, and the times taken to reach the 5%, 35.3% and 85.3% of the final output and then applying a set of tuning equations. The tuning equations approximate the controller that minimizes the Integral of Absolute Error (IAE) of the disturbance response for a model with three real poles and time delay and are very accurate for a wide range of non oscillatory stable systems. The user can select the desired robustness (through the required maximum of the Sensitivity function (Ms)), as a difference with usual methods that allow only to choose among two or three predefined robustness. The PI controller that minimizes the disturbance IAE is defined by default, but the user can also select a detuning factor to define slower controllers with the same robustness, allowing to find the desired compromise between performance and actuator activity due to sensor measurement noise. An application for Android, that can be downloaded for free, and a web based application, have been developed to implement the tuning procedure.

Two Electrical Engineers, One Problem, and Evolution Produced the Same Solution: A Historical Note.

This note adds historical context into solving the problem of improving the speed of the step response of a low-order plant in two different types of control systems, a chemical mixing system and the human saccadic system. Two electrical engineers studied the above problem: one to understand and model how nature and evolution solved it and the other to design a control system to solve it in a man-made commercial system. David A. Robinson discovered that fast and accurate saccades were produced by a pulse-step of neural innervation applied to the extraocular plant. Leonidas M. Mantgiaris invented a method to achieve rapid and accurate chemical mixing by applying a large stimulus for a short period of time and then replacing it with the desired steady-state value (i.e., a "pulse-step" input). Thus, two humans used their brains to: 1) determine how the human brain produced human saccades; and 2) invent a control-system method to produce fast and accurate chemical mixing. That the second person came up with the same method by which his own brain was making saccades may shed light on the question of whether the human brain can fully understand itself.

Evaluation of Impulse-Oscillometric Extravasation Prevention.

Infusion liquid extravasation occurs in up to 6% of all intensive care patients and up to 78% for neonates. Currently, emerging extravasation cannot be detected. An impulse-oscillometric method to detect the onset of extravasation is tested and evaluated in vitro. A pinch valve compresses the infusion line, an impulse is formed, and the pressure response is recorded at the peripheral vein catheter. The response of this catheter-sensor-system is analysed by measuring the transient-step response (n = 10) for an opened and closed pinch valve. Trials utilising porcine shanks (n = 15) are performed with venous and extravasational catheter placement. The fundamental frequency, maximum amplitude, damping and decay constant of the pressure response are tested for differences between venous and extravasational placement. The response of the catheter-sensor-system shows no significant differences between an opened or closed pinch valve. The maximum amplitude, frequency, damping and decay constant of the pressure response differ highly significant for venous and extravasational catheter placement (p < .001). The parameters also differ depending on the presence of infusion liquid flow (p < .001). The method enables the detection of the onset of extravasation. Further tests are performed to investigate the relationships between impulse response and hydraulic impedance.

Investigation of Impulse Oscillometry for the Detection of Extravasations using Design of Experiments and an Infusion Simulator.

Extravasation is a phenomenon that occurs when the infusion solution misses the vein and enters the surrounding tissue. We developed a sensor prototype utilising impulse oscillometry to detect extravasations at an early stage. A hydraulic impulse is injected into the infusion line to observe and analyse its progress. The aim of this study was to determine the tissue parameters that might influence the sensor measurement signal and signal changes during extravasation. We developed a simulator that simulates infusions and extravasations to test the prototype. Tissue-specific parameters can be adjusted independently. The effects of the tissue parameters, including blood pressure, blood flow, blood density, blood viscosity, vein diameter, venous wall thickness, and tissue modulus of elasticity, were investigated using the design of experiments method. The parameter values were varied between two levels and tested across 16 experiments. Blood pressure, blood viscosity, vein diameter, and venous compliance demonstrated the greatest impact on the sensor signal (p < .001). The other parameters showed negligible effects. Significant differences (p = .006) in the pressure signal of the sensor could be observed when the catheter changed from the venous position to the extravasal position.

Transition from double-leg to single-leg stance in the assessment of postural stability.

Kinematic characteristics of the double-leg stance (DLS) to a single-leg stance (SLS) transition were analyzed in a group of young adolescent girls to assess their postural stability control. Twenty volunteers participated in a single experimental session during which their postural stability was assessed based upon the center of pressure (COP) trajectories during the transitions in two typical sensory conditions: with eyes open (EO) and with eyes closed (EC). To quantify the postural control we applied Fitts' model treating the postural sway as the noise at the initial and the target setpoint control. Results showed that in young healthy subjects characteristics of the transition to either left or right single-leg stance were quite symmetrical. The postural sway at the target posture was characterized by the double increase of postural sway when tested with EO and by the almost quadrupled amount of sway in EC trials. The sway at the target resulted in the decline of the COP mean and peak velocity proportionally to the movement index of difficulty (ID). The estimated ID value increased by 74% in EC trials while the probability of instability increased to 70%. The DLS-SLS test can be recommended for clinical and laboratory assessment of postural stability.

Heating-up control with delay-free output prediction for industrial jacketed reactors based on step response identification.

To improve the heating-up control performance for industrial jacketed reactors typically involved with long input delay, a predictor-based two-degree-of-freedom (2DOF) control scheme is proposed for the heating-up process operation, based on model identification from a practical step response test. By performing a simple step test (i.e., turning on the electrical heater with certain power (e.g., 50% or 100% of the heating power) to observe the heating-up temperature response), a transfer function identification method is developed to establish an integrating type process model with time delay for describing fundamental dynamics of the heating-up response. Based on the identified model, a predictor-based 2DOF control structure is established, where the delay-free output prediction is obtained by constructing two filters. The 2DOF controllers are analytically derived by proposing the desired transfer functions for the set-point tracking and load disturbance rejection, respectively. There is a single adjustable parameter in each controller (or filter), which may be monotonically tuned to obtain the desired control (or prediction) performance. Illustrative examples from the existing references and a practical application to a 4-liter jacketed reactor for pharmaceutical crystallization are given to demonstrate the effectiveness and advantage of the proposed identification and control methods in comparison with the existing methods.

Determination of the temperature vs power dynamic behavior of a cryocooler via two independent methods in time and frequency domain.

This report deals with the analysis of a cryocooler as a linear dynamical system around a set point, over a range of temperatures where the thermal properties can be considered constant. The accurate knowledge of the cryocooler temperature dependence with a time dependent power stimulus allows to analyze the thermodynamical properties of the system and understand the power flow related, for example, to the cryocooler temperature fluctuations. This is useful for the design of efficient thermal dampers that are necessary for the thermal stabilization of the device under test Sosso et al. [1], Trinchera et al. [2]. Two different and independent methods for deriving the cooler dynamic (i.e. non-stationary) behavior are described using the two main approaches to mathematically represent a dynamical system: step response and transfer function. •Using both approaches we were able to cross check results and provide an estimate of the accuracy of each method.•The instrumentation required is typically available in physics and engineering laboratories.•These results provide insights on cryocooler thermodynamics and design tools for cryocooler engineering.

Generalized characteristic ratios assignment for commensurate fractional order systems with one zero.

In this paper, a new method for determination of the desired characteristic equation and zero location of commensurate fractional order systems is presented. The concept of the characteristic ratio is extended for zero-including commensurate fractional order systems. The generalized version of characteristic ratios is defined such that the time-scaling property of characteristic ratios is also preserved. The monotonicity of the magnitude frequency response is employed to assign the generalized characteristic ratios for commensurate fractional order transfer functions with one zero. A simple pattern for characteristic ratios is proposed to reach a non-overshooting step response. Then, the proposed pattern is revisited to reach a low overshoot (say for example 2%) step response. Finally, zero-including controllers such as fractional order PI or lag (lead) controllers are designed using generalized characteristic ratios assignment method. Numerical simulations are provided to show the efficiency of the so designed controllers.

Changes in stepping response to lateral perturbations immediately following a single bout of physical activity.

BACKGROUND AND PURPOSE: Fatiguing exercise can adversely alter postural stability and therefore may contribute to falling. However, older adults rarely perform exercise to fatigue. This study aimed to determine whether undertaking a single bout of moderate-intensity physical activity, similar to that experienced during daily activity or rehabilitation, altered the ability to recover balance with an outward step response to a lateral perturbation. METHODS: Thirty-four healthy older adults (mean: 76±5 years) and 31 healthy young adults (29±6 years) underwent a 14-minute, self-paced, moderate-intensity physical activity protocol. Before and immediately after the protocol, their responses to lateral waist-pull perturbations were recorded. For participants who used a single outward step response before and after the perturbation, the changes to the timing of the step phases and the hip abductor muscle activity onsets were compared. RESULTS: Young adults responded with an outward step in 55% of trials before and 70% after activity, whereas this frequency was 35% before and 36% after among older adults. When performed, the timing of steps and muscle activity onsets were not adversely altered following the physical activity in either group, apart from a slightly later stance limb gluteus medius onset after activity, found in both groups. CONCLUSIONS: Before and after activity, older adults responded with a single outward step to arrest a fall less frequently than young adults. This may place older adults at risk of overbalancing. However, when responding with this strategy, both young and older adults demonstrated few changes immediately following moderate-intensity physical activity compared with before. They appear to be not adversely affected by moderate physical activity.

An automatic selections method for cerebral blood flow autoregulation signals from neonates

Interpretation and quantification of cerebral blood flow autoregulation can be carreid out from step responses to arterial blood pressure changes estimated with various identification methods. However estimates usually need to be visually inspected to rejected some that are not physiologically acceptable...