Evaporation-controlled dripping-onto-substrate (DoS) extensional rheology of viscoelastic polymer solutions.

Extensional flow properties of polymer solutions in volatile solvents govern many industrially-relevant coating processes, but existing instrumentation lacks the environment necessary to control evaporation. To mitigate evaporation during dripping-onto-substrate (DoS) extensional rheology measurements, we developed a chamber to enclose the sample in an environment saturated with solvent vapor. We validated the evaporation-controlled DoS device by measuring a model high molecular weight polyethylene oxide (PEO) in various organic solvents both inside and outside of the chamber. Evaporation substantially increased the extensional relaxation time [Formula: see text] for PEO in volatile solvents like dichloromethane and chloroform. PEO/chloroform solutions displayed an over 20-fold increase in [Formula: see text] due to the formation of an evaporation-induced surface film; evaporation studies confirmed surface features and skin formation reminiscent of buckling instabilities commonly observed in drying polymer solutions. Finally, the relaxation times of semi-dilute PEO/chloroform solutions were measured with environmental control, where [Formula: see text] scaled with concentration by the exponent [Formula: see text]. These measurements validate the evaporation-controlled DoS environment, and confirm that chloroform is a good solvent for PEO, with a Flory exponent of [Formula: see text]. Our results are the first to control evaporation during DoS extensional rheology, and provide guidelines establishing when environmental control is necessary to obtain accurate rheological parameters.

Part 1: Surgical Correction in 231 Trigonocephaly Patients - The Alder Hey Experience.

ABSTRACT: Isolated metopic synostosis presents with a range of severity, from a palpable ridge as the sole presenting feature to a constellation of features resulting in trigonocephaly. At our unit, patients on the moderate to severe end of the phenotypic spectrum of trigonocephaly are offered fronto-orbital advancement and remodeling. The authors present our series of trigonocephaly patients who have undergone surgical correction. From January 2000 to January 2020, the authors operated on 231 patients with trigonocephaly. The average age at surgery was 18 months, with an average follow-up of 77.4 months. Seventy-nine percent of patients had no comorbidity. Ten percent of patients sustained a dural tear with no long-term consequences. The total early complication rate was 12.1%. The most common early complications were wound infection and wound dehiscence at 7.4% and 3.9% respectively. The total reoperation rate was 6.5%. The introduction of infection prevention and control measures over the 2 decades at our unit reduced the reoperation rate to 1.1%. The most common late complication was temporal recession in 20.8% of patients, none of whom required aesthetic correction. The recurrence rate of a metopic ridge was 2.3% with no patients requiring further surgery. None of our patients required calvarial remodeling for raised intracranial pressure after the primary fronto-orbital advancement and remodeling. There were no life-threatening complications or mortalities in our cohort. The authors present recommendations which include an infection control care bundle, cessation of surgical drains, and practice adjustments to reduce risks of infection and risk of requiring further calvarial remodelling for raised intracranial pressure.

Matlab software for impedance spectroscopy designed for neuroscience applications.

BACKGROUND: Metal electrodes are a mainstay of neuroscience. Characterization of the electrical impedance properties of these cuffs is important to ensure successful and repeatable fabrication, achieve a target impedance, revise novel designs, and quantify the success or failure of implantation and any potential subsequent damage or encapsulation by scar tissue. NEW METHODS: Impedances are frequently characterized using lumped-parameter circuit models of the electrode-electrolyte interface. Open-source tools to gather and analyze these frequency sweep data are lacking. Here, we present such software, in the form of Matlab code, which includes a GUI. It automatically acquires frequency sweep data and subsequently fits a simplified Randles model to these data, over a user specified frequency range, providing the user with the model parameter estimates. Also, it can measure an unknown impedance of an element over a range of frequencies, as long as an external resistor can be added for the measurements. RESULTS: The tool was tested on five bright platinum nerve cuffs in vitro. The average charge transfer resistance, solution resistance, CPE value, and impedance magnitude were estimated. COMPARISON TO EXISTING METHODS: The measured values of the impedance of cuffs were in agreement with the literature (Wei and Grill, 2009). Variation between cuffs fabricated as consistently as possible amounted to 10% for impedance magnitude and 4° for impedance phase. CONCLUSION: The results show that this low-cost tool can be used to characterize a cuff across different conditions including after implantation. The latter makes it useful for a longer-term study of electrode viability.

Thermally Rearranged Polymer Membranes Containing Tröger's Base Units Have Exceptional Performance for Air Separations.

The influence of segmental chain motion on the gas separation performance of thermally rearranged (TR) polymer membranes is established for TR polybenzoxazoles featuring Tröger's base (TB) monomer subunits as exceptionally rigid sites of contortion along the polymer backbone. These polymers are accessed from solution-processable ortho-acetate functionalized polyimides, which are readily synthesized as high-molecular-weight polymers for membrane casting. We find that thermal rearrangement leads to a small increase in d-spacing between polymer chains and a dramatic pore-network reconfiguration that increases both membrane permeability and O2 /N2 selectivity, putting its performance above the 2015 upper bound.

A benchtop biorobotic platform for in vitro observation of muscle-tendon dynamics with parallel mechanical assistance from an elastic exoskeleton.

We present a novel biorobotic framework comprised of a biological muscle-tendon unit (MTU) mechanically coupled to a feedback controlled robotic environment simulation that mimics in vivo inertial/gravitational loading and mechanical assistance from a parallel elastic exoskeleton. Using this system, we applied select combinations of biological muscle activation (modulated with rate-coded direct neural stimulation) and parallel elastic assistance (applied via closed-loop mechanical environment simulation) hypothesized to mimic human behavior based on previously published modeling studies. These conditions resulted in constant system-level force-length dynamics (i.e., stiffness), reduced biological loads, increased muscle excursion, and constant muscle average positive power output-all consistent with laboratory experiments on intact humans during exoskeleton assisted hopping. Mechanical assistance led to reduced estimated metabolic cost and MTU apparent efficiency, but increased apparent efficiency for the MTU+Exo system as a whole. Findings from this study suggest that the increased natural resonant frequency of the artificially stiffened MTU+Exo system, along with invariant movement frequencies, may underlie observed limits on the benefits of exoskeleton assistance. Our novel approach demonstrates that it is possible to capture the salient features of human locomotion with exoskeleton assistance in an isolated muscle-tendon preparation, and introduces a powerful new tool for detailed, direct examination of how assistive devices affect muscle-level neuromechanics and energetics.

Unconstrained muscle-tendon workloops indicate resonance tuning as a mechanism for elastic limb behavior during terrestrial locomotion.

In terrestrial locomotion, there is a missing link between observed spring-like limb mechanics and the physiological systems driving their emergence. Previous modeling and experimental studies of bouncing gait (e.g., walking, running, hopping) identified muscle-tendon interactions that cycle large amounts of energy in series tendon as a source of elastic limb behavior. The neural, biomechanical, and environmental origins of these tuned mechanics, however, have remained elusive. To examine the dynamic interplay between these factors, we developed an experimental platform comprised of a feedback-controlled servo-motor coupled to a biological muscle-tendon. Our novel motor controller mimicked in vivo inertial/gravitational loading experienced by muscles during terrestrial locomotion, and rhythmic patterns of muscle activation were applied via stimulation of intact nerve. This approach was based on classical workloop studies, but avoided predetermined patterns of muscle strain and activation-constraints not imposed during real-world locomotion. Our unconstrained approach to position control allowed observation of emergent muscle-tendon mechanics resulting from dynamic interaction of neural control, active muscle, and system material/inertial properties. This study demonstrated that, despite the complex nonlinear nature of musculotendon systems, cyclic muscle contractions at the passive natural frequency of the underlying biomechanical system yielded maximal forces and fractions of mechanical work recovered from previously stored elastic energy in series-compliant tissues. By matching movement frequency to the natural frequency of the passive biomechanical system (i.e., resonance tuning), muscle-tendon interactions resulting in spring-like behavior emerged naturally, without closed-loop neural control. This conceptual framework may explain the basis for elastic limb behavior during terrestrial locomotion.

Timing matters: tuning the mechanics of a muscle-tendon unit by adjusting stimulation phase during cyclic contractions.

A growing body of research on the mechanics and energetics of terrestrial locomotion has demonstrated that elastic elements acting in series with contracting muscle are critical components of sustained, stable and efficient gait. Far fewer studies have examined how the nervous system modulates muscle-tendon interaction dynamics to optimize 'tuning' or meet varying locomotor demands. To explore the fundamental neuromechanical rules that govern the interactions between series elastic elements (SEEs) and contractile elements (CEs) within a compliant muscle-tendon unit (MTU), we used a novel work loop approach that included implanted sonomicrometry crystals along muscle fascicles. This enabled us to decouple CE and SEE length trajectories when cyclic strain patterns were applied to an isolated plantaris MTU from the bullfrog (Lithobates catesbeianus). Using this approach, we demonstrate that the onset timing of muscle stimulation (i.e. stimulation phase) that involves a symmetrical MTU stretch-shorten cycle during active force production results in net zero mechanical power output, and maximal decoupling of CE and MTU length trajectories. We found it difficult to 'tune' the muscle-tendon system for strut-like isometric force production by adjusting stimulation phase only, as the zero power output condition involved significant positive and negative mechanical work by the CE. A simple neural mechanism - adjusting muscle stimulation phase - could shift an MTU from performing net zero to net positive (energy producing) or net negative (energy absorbing) mechanical work under conditions of changing locomotor demand. Finally, we show that modifications to the classical work loop paradigm better represent in vivo muscle-tendon function during locomotion.

More is not always better: modeling the effects of elastic exoskeleton compliance on underlying ankle muscle-tendon dynamics.

Development of robotic exoskeletons to assist/enhance human locomotor performance involves lengthy prototyping, testing, and analysis. This process is further convoluted by variability in limb/body morphology and preferred gait patterns between individuals. In an attempt to expedite this process, and establish a physiological basis for actuator prescription, we developed a simple, predictive model of human neuromechanical adaptation to a passive elastic exoskeleton applied at the ankle joint during a functional task. We modeled the human triceps surae-Achilles tendon muscle tendon unit (MTU) as a single Hill-type muscle, or contractile element (CE), and series tendon, or series elastic element (SEE). This modeled system was placed under gravitational load and underwent cyclic stimulation at a regular frequency (i.e. hopping) with and without exoskeleton (Exo) assistance. We explored the effect that both Exo stiffness (kExo) and muscle activation (Astim) had on combined MTU and Exo (MTU + Exo), MTU, and CE/SEE mechanics and energetics. Model accuracy was verified via qualitative and quantitative comparisons between modeled and prior experimental outcomes. We demonstrated that reduced Astim can be traded for increased kExo to maintain consistent MTU + Exo mechanics (i.e. average positive power (P⁺mech) output) from an unassisted condition (i.e. kExo = 0 kN · m⁻¹). For these regions of parameter space, our model predicted a reduction in MTU force, SEE energy cycling, and metabolic rate (Pmet), as well as constant CE P⁺mech output compared to unassisted conditions. This agreed with previous experimental observations, demonstrating our model's predictive ability. Model predictions also provided insight into mechanisms of metabolic cost minimization, and/or enhanced mechanical performance, and we concluded that both of these outcomes cannot be achieved simultaneously, and that one must come at the detriment of the other in a spring-assisted compliant MTU.

Exploiting elasticity: Modeling the influence of neural control on mechanics and energetics of ankle muscle-tendons during human hopping.

We present a simplified Hill-type model of the human triceps surae-Achilles tendon complex working on a gravitational-inertial load during cyclic contractions (i.e. vertical hopping). Our goal was to determine the role that neural control plays in governing muscle, or contractile element (CE), and tendon, or series elastic element (SEE), mechanics and energetics within a compliant muscle-tendon unit (MTU). We constructed a 2D parameter space consisting of many combinations of stimulation frequency and magnitude (i.e. neural control strategies). We compared the performance of each control strategy by evaluating peak force and average positive mechanical power output for the system (MTU) and its respective components (CE, SEE), force-length (F-L) and -velocity (F-V) operating point of the CE during active force production, average metabolic rate for the CE, and both MTU and CE apparent efficiency. Our results suggest that frequency of stimulation plays a primary role in governing whole-MTU mechanics. These include the phasing of both activation and peak force relative to minimum MTU length, average positive power, and apparent efficiency. Stimulation amplitude was primarily responsible for governing average metabolic rate and within MTU mechanics, including peak force generation and elastic energy storage and return in the SEE. Frequency and amplitude of stimulation both played integral roles in determining CE F-L operating point, with both higher frequency and amplitude generally corresponding to lower CE strains, reduced injury risk, and elimination of the need for passive force generation in the CE parallel elastic element (PEE).

Elastic ankle exoskeletons reduce soleus muscle force but not work in human hopping.

Inspired by elastic energy storage and return in tendons of human leg muscle-tendon units (MTU), exoskeletons often place a spring in parallel with an MTU to assist the MTU. However, this might perturb the normally efficient MTU mechanics and actually increase active muscle mechanical work. This study tested the effects of elastic parallel assistance on MTU mechanics. Participants hopped with and without spring-loaded ankle exoskeletons that assisted plantar flexion. An inverse dynamics analysis, combined with in vivo ultrasound imaging of soleus fascicles and surface electromyography, was used to determine muscle-tendon mechanics and activations. Whole body net metabolic power was obtained from indirect calorimetry. When hopping with spring-loaded exoskeletons, soleus activation was reduced (30-70%) and so was the magnitude of soleus force (peak force reduced by 30%) and the average rate of soleus force generation (by 50%). Although forces were lower, average positive fascicle power remained unchanged, owing to increased fascicle excursion (+4-5 mm). Net metabolic power was reduced with exoskeleton assistance (19%). These findings highlighted that parallel assistance to a muscle with appreciable series elasticity may have some negative consequences, and that the metabolic cost associated with generating force may be more pronounced than the cost of doing work for these muscles.

Nanoparticle mediated thermal ablation of breast cancer cells using a nanosecond pulsed electric field.

In the past, ablation of cancer cells using radiofrequency heating techniques has been demonstrated, but the current methodology has many flaws, including inconsistent tumor ablation and significant ablation of normal cells. Other researchers have begun to develop a treatment that is more selective for cancer cells using metallic nanoparticles and constant electric field exposure. In these studies, cell necrosis is induced by heating antibody functionalized metallic nanoparticles attached to cancer cells. Our approach to studying this phenomenon is to use similarly functionalized metallic nanoparticles that are specific for the T47D breast cancer cell line, exposing these nanoparticle cell conjugates to a nanosecond pulsed electric field. Using fluorescent, polystyrene-coated, iron-oxide nanoparticles, the results of our pilot study indicated that we were able to ablate up to approximately 80% of the cells using 60 ns pulses in increasing numbers of pulses and up to approximately 90% of the cells using 300 ns pulses in increasing numbers of pulses. These quantities of ablated cells were achieved using a cumulative exposure time 6 orders of magnitude less than most in vitro constant electric field studies.

Combined diazepam and HDAC inhibitor treatment protects against seizures and neuronal damage caused by soman exposure.

The occurrence of status epilepticus (SE) is considered the main cause of brain lesions and morphological alterations, such as hippocampal neuron loss, that result in chronic epilepsy. Previous work demonstrated the convulsive and widespread neuropathological effects of soman, an organophosphorus compound that causes SE and severe recurrent seizures as a result of exposure. Seizures begin rapidly after exposure, can continue for hours, and contribute to prolonged physical incapacitation of the victim. This study attempts to identify anticonvulsive and neuroprotective drugs against soman exposure. Male Sprague-Dawley rats were exposed to 1.0 LD(50) soman. EEGraphical and neuropathological (Fluoro-Jade B staining) effects were analyzed at 72 h post-exposure to soman and subsequent treatments with diazepam (DZP) alone or in combination with histone deacetylase inhibitors, suberoylanilide hydroxamic acid (SAHA) or valproic acid (VPA). The extent of brain damage was dependent on the length of SE and not on the number of recurrent seizures. DZP treatment alone decreased SE time and damage in hippocampus, amygdala, thalamus and cortex, but not in piriform nuclei. The combination of DZP and VPA 100 mg/kg showed more anticonvulsive effects, decreased SE time, and afforded more neuroprotection in the hippocampus, mainly the ventral portion. The combination DZP and SAHA 25 mg/kg was more neuroprotective, but not more anticonvulsant than DZP alone. The DZP combination with VPA HDAC inhibitor proved to be a good treatment for SE and neuronal damage caused by soman exposure.

Influence of parallel spring-loaded exoskeleton on ankle muscle-tendon dynamics during simulated human hopping.

Robotic assistance for rehabilitation and enhancement of human locomotion has become a major goal of biomedical engineers in recent years. While significant progress to this end has been made in the fields of neural interfacing and control systems, little has been done to examine the effects of mechanical assistance on the biomechanics of underlying muscle-tendon systems. Here, we model the effects of mechanical assistance via a passive spring acting in parallel with the triceps surae-Achilles tendon complex during cyclic hopping in humans. We examine system dynamics over a range of biological muscle activation and exoskeleton spring stiffness. We find that, in most cases, uniform cyclic mechanical power production of the coupled system is achieved. Furthermore, unassisted power production can be reproduced throughout parameter space by trading off decreases in muscle activation with increases in ankle exoskeleton spring stiffness. In addition, we show that as mechanical assistance increases the biological muscle-tendon unit becomes less 'tuned' resulting in higher mechanical power output from active components of muscle despite large reductions in required force output.