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Sensorimotor control can be impaired by slacked muscle spindles. This was shown for reflex responses and, recently, also for muscular stability in the sense of Adaptive Force (AF). The slack in muscle spindles was generated by contracting the lengthened muscle followed by passive shortening. AF was suggested to specifically reflect sensorimotor control since it requires tension-length control in adaptation to an increasing load. This study investigated AF parameters in reaction to another, manually performed slack procedure in a preselected sample (n = 13). The AF of 11 elbow and 12 hip flexors was assessed by an objectified manual muscle test (MMT) using a handheld device. Maximal isometric AF was significantly reduced after manual spindle technique vs. regular MMT. Muscle lengthening started at 64.93 & PLUSMN; 12.46% of maximal voluntary isometric contraction (MVIC). During regular MMT, muscle length could be maintained stable until 92.53 & PLUSMN; 10.12% of MVIC. Hence, muscular stability measured by AF was impaired after spindle manipulation. Force oscillations arose at a significantly lower level for regular vs. spindle. This supports the assumption that they are a prerequisite for stable adaptation. Reduced muscular stability in reaction to slack procedures is considered physiological since sensory information is misled. It is proposed to use slack procedures to test the functionality of the neuromuscular system, which is relevant for clinical practice.
Introduction
Balance is vital for human health and experiments have been conducted to measure the mechanisms of postural control, for example studying reflex responses to simulated perturbations. Such studies are frequent in walking but less common in running, and an understanding of reflex responses to trip-like disturbances could enhance our understanding of human gait and improve approaches to training and rehabilitation. Therefore, the primary aim of this study was to investigate the technical validity and reliability of a treadmill running protocol with perturbations. A further exploratory aim was to evaluate the associated neuromuscular reflex responses to the perturbations, in the lower limbs.
Methods
Twelve healthy participants completed a running protocol (9 km/h) test-retest (2 weeks apart), whereby 30 unilateral perturbations were executed via the treadmill belts (presets:2.0 m/s amplitude;150 ms delay (post-heel contact);100ms duration). Validity of the perturbations was assessed via mean +/- SD comparison, percentage error calculation between the preset and recorded perturbation characteristics (PE%), and coefficient of variation (CV%). Test-retest reliability (TRV%) and Bland-Altman analysis (BLA; bias +/- 1.96 * SD) was calculated for reliability. To measure reflex activity, electromyography (EMG) was applied in both legs. EMG amplitudes (root mean square normalized to unperturbed strides) and latencies [ms] were analysed descriptively.
Results
Left-side perturbation amplitude was 1.9 +/- 0.1 m/s, delay 105 +/- 2 ms, and duration 78 +/- 1 ms. Right-side perturbation amplitude was 1.9 +/- 0.1 m/s, delay 118 +/- 2 ms, duration 78 +/- 1 ms. PE% ranged from 5-30% for the recorded perturbations. CV% of the perturbations ranged from 19.5-76.8%. TRV% for the perturbations was 6.4-16.6%. BLA for the left was amplitude: 0.0 +/- 0.3m/s, delay: 0 +/- 17 ms, duration: 2 +/- 13 ms, and for the right was amplitude: 0.1 +/- 0.7, delay: 4 +/- 40 ms, duration: 1 +/- 35 ms. EMG amplitudes ranged from 175 +/- 141%-454 +/- 359% in both limbs. Latencies were 109 +/- 12-116 +/- 23 ms in the tibialis anterior, and 128 +/- 49-157 +/- 20 ms in the biceps femoris.
Discussion
Generally, this study indicated sufficient validity and reliability of the current setup considering the technical challenges and limitations, although the reliability of the right-sided perturbations could be questioned. The protocol provoked reflex responses in the lower extremities, especially in the leading leg. Acute neuromusculoskeletal adjustments to the perturbations could be studied and compared in clinical and healthy running populations, and the protocol could be utilised to monitor chronic adaptations to interventions over time.
High-solid-content polystyrene and polyvinyl acetate dispersions of polymer particles with a 50 nm to 500 nm mean particle diameter and 12-55% (w/w) solid content have been produced via emulsion polymerization and characterized regarding their optical and physical properties. Both systems have been analyzed with common particle-size-measuring techniques like dynamic light scattering (DLS) and static light scattering (SLS) and compared to inline particle size distribution (PSD) measurements via photon density wave (PDW) spectroscopy in undiluted samples. It is shown that particle size measurements of undiluted polystyrene dispersions are in good agreement between analysis methods. However, for polyvinyl acetate particles, size determination is challenging due to bound water in the produced polymer. For the first time, water-swelling factors were determined via an iterative approach of PDW spectroscopy error (X-2) minimization. It is shown that water-swollen particles can be analyzed in high-solid-content solutions and their physical properties can be assumed to determine the refractive index, density, and volume fraction in dispersion. It was found that assumed water swelling improved the reduced scattering coefficient fit by PDW spectroscopy by up to ten times and particle size determination was refined and enabled. Particle size analysis of the water-swollen particles agreed well with offline-based state-of-the-art techniques.
How to confuse motor control
(2023)
Adaptation to external forces relies on a well-functioning proprioceptive system including muscle spindle afferents. Muscle length and tension control in reaction to external forces is most important regarding the Adaptive Force (AF). This study investigated the effect of different procedures, which are assumed to influence the function of muscle spindles, on the AF. Elbow flexors of 12 healthy participants (n = 19 limbs) were assessed by an objectified manual muscle test (MMT) with different procedures: regular MMT, MMT after precontraction (self-estimated 20% MVIC) in lengthened position with passive return to test position (CL), and MMT after CL with a second precontraction in test position (CL-CT). During regular MMTs, muscles maintained their length up to 99.7% +/- 1.0% of the maximal AF (AF(max)). After CL, muscles started to lengthen at 53.0% +/- 22.5% of AF(max). For CL-CT, muscles were again able to maintain the static position up to 98.3% +/- 5.5% of AF(max). AFiso(max) differed highly significantly between CL vs. CL-CT and regular MMT. CL was assumed to generate a slack of muscle spindles, which led to a substantial reduction of the holding capacity. This was immediately erased by a precontraction in the test position. The results substantiate that muscle spindle sensitivity seems to play an important role for neuromuscular functioning and musculoskeletal stability.
Effects of exercise treatment on functional outcome parameters in mid-portion achilles tendinopathy
(2023)
Exercise interventions are evident in the treatment of mid-portion Achilles tendinopathy (AT). However, there is still a lack of knowledge concerning the effect of different exercise treatments on improving a specific function (e.g., strength) in this population. Thus, this study aimed to systematically review the effect of exercise treatments on different functional outcomes in mid-portion AT. An electronic database of Pubmed, Web of Science, and Cochrane Central Register of Controlled Trials were searched from inception to 21 February 2023. Studies that investigated changes in plantar flexor function with exercise treatments were considered in mid-portion AT. Only randomized controlled trials (RCTs) and clinical controlled trials (CCTs) were included. Functional outcomes were classified by kinetic (e.g., strength), kinematic [e.g., ankle range of motion (ROM)], and sensorimotor (e.g., balance index) parameters. The types of exercise treatments were classified into eccentric, concentric, and combined (eccentric plus concentric) training modes. Quality assessment was appraised using the Physiotherapy Evidence Database scale for RCTs, and the Joanna Briggs Institute scale for CCTs. The search yielded 2,260 records, and a total of ten studies were included. Due to the heterogeneity of the included studies, a qualitative synthesis was performed. Eccentric training led to improvements in power outcomes (e.g., height of countermovement jump), and in strength outcomes (e.g., peak torque). Concentric training regimens showed moderate enhanced power outcomes. Moreover, one high-quality study showed an improvement in the balance index by eccentric training, whereas the application of concentric training did not. Combined training modalities did not lead to improvements in strength and power outcomes. Plantarflexion and dorsiflexion ROM measures did not show relevant changes by the exercise treatments. In conclusion, eccentric training is evident in improving strength outcomes in AT patients. Moreover, it shows moderate evidence improvements in power and the sensorimotor parameter "balance index". Concentric training presents moderate evidence in the power outcomes and can therefore be considered as an alternative to improve this function. Kinematic analysis of plantarflexion and dorsiflexion ROM might not be useful in AT people. This study expands the knowledge what types of exercise regimes should be considered to improve the functional outcomes in AT.
Giving emotional intelligence to machines can facilitate the early detection and prediction of mental diseases and symptoms. Electroencephalography (EEG)-based emotion recognition is widely applied because it measures electrical correlates directly from the brain rather than indirect measurement of other physiological responses initiated by the brain. Therefore, we used non-invasive and portable EEG sensors to develop a real-time emotion classification pipeline. The pipeline trains different binary classifiers for Valence and Arousal dimensions from an incoming EEG data stream achieving a 23.9% (Arousal) and 25.8% (Valence) higher F1-Score on the state-of-art AMIGOS dataset than previous work. Afterward, the pipeline was applied to the curated dataset from 15 participants using two consumer-grade EEG devices while watching 16 short emotional videos in a controlled environment. Mean F1-Scores of 87% (Arousal) and 82% (Valence) were achieved for an immediate label setting. Additionally, the pipeline proved to be fast enough to achieve predictions in real-time in a live scenario with delayed labels while continuously being updated. The significant discrepancy from the readily available labels on the classification scores leads to future work to include more data. Thereafter, the pipeline is ready to be used for real-time applications of emotion classification.
Pressure overload in patients with aortic valve stenosis and volume overload in mitral valve regurgitation trigger specific forms of cardiac remodeling; however, little is known about similarities and differences in myocardial proteome regulation. We performed proteome profiling of 75 human left ventricular myocardial biopsies (aortic stenosis = 41, mitral regurgitation = 17, and controls = 17) using high-resolution tandem mass spectrometry next to clinical and hemodynamic parameter acquisition. In patients of both disease groups, proteins related to ECM and cytoskeleton were more abundant, whereas those related to energy metabolism and proteostasis were less abundant compared with controls. In addition, disease group-specific and sex-specific differences have been observed. Male patients with aortic stenosis showed more proteins related to fibrosis and less to energy metabolism, whereas female patients showed strong reduction in proteostasis-related proteins. Clinical imaging was in line with proteomic findings, showing elevation of fibrosis in both patient groups and sex differences. Disease-and sex-specific proteomic profiles provide insight into cardiac remodeling in patients with heart valve disease and might help improve the understanding of molecular mechanisms and the development of individualized treatment strategies.
Introduction:
Hydrocortisone is the standard of care in cortisol replacement therapy for congenital adrenal hyperplasia patients. Challenges in mimicking cortisol circadian rhythm and dosing individualization can be overcome by the support of mathematical modelling. Previously, a non-linear mixed-effects (NLME) model was developed based on clinical hydrocortisone pharmacokinetic (PK) pediatric and adult data. Additionally, a physiologically-based pharmacokinetic (PBPK) model was developed for adults and a pediatric model was obtained using maturation functions for relevant processes. In this work, a middle-out approach was applied. The aim was to investigate whether PBPK-derived maturation functions could provide a better description of hydrocortisone PK inter-individual variability when implemented in the NLME framework, with the goal of providing better individual predictions towards precision dosing at the patient level.
Methods:
Hydrocortisone PK data from 24 adrenal insufficiency pediatric patients and 30 adult healthy volunteers were used for NLME model development, while the PBPK model and maturation functions of clearance and cortisol binding globulin (CBG) were developed based on previous studies published in the literature.
Results:
Clearance (CL) estimates from both approaches were similar for children older than 1 year (CL/F increasing from around 150 L/h to 500 L/h), while CBG concentrations differed across the whole age range (CBG(NLME) stable around 0.5 mu M vs. steady increase from 0.35 to 0.8 mu M for CBG (PBPK)). PBPK-derived maturation functions were subsequently included in the NLME model. After inclusion of the maturation functions, none, a part of, or all parameters were re-estimated. However, the inclusion of CL and/or CBG maturation functions in the NLME model did not result in improved model performance for the CL maturation function (& UDelta;OFV > -15.36) and the re-estimation of parameters using the CBG maturation function most often led to unstable models or individual CL prediction bias.
Discussion:
Three explanations for the observed discrepancies could be postulated, i) non-considered maturation of processes such as absorption or first-pass effect, ii) lack of patients between 1 and 12 months, iii) lack of correction of PBPK CL maturation functions derived from urinary concentration ratio data for the renal function relative to adults. These should be investigated in the future to determine how NLME and PBPK methods can work towards deriving insights into pediatric hydrocortisone PK.
The ZuCo benchmark on cross-subject reading task classification with EEG and eye-tracking data
(2023)
We present a new machine learning benchmark for reading task classification with the goal of advancing EEG and eye-tracking research at the intersection between computational language processing and cognitive neuroscience. The benchmark task consists of a cross-subject classification to distinguish between two reading paradigms: normal reading and task-specific reading. The data for the benchmark is based on the Zurich Cognitive Language Processing Corpus (ZuCo 2.0), which provides simultaneous eye-tracking and EEG signals from natural reading of English sentences. The training dataset is publicly available, and we present a newly recorded hidden testset. We provide multiple solid baseline methods for this task and discuss future improvements. We release our code and provide an easy-to-use interface to evaluate new approaches with an accompanying public leaderboard: .
State- and private-led search-and-rescue are hypothesized to foster irregular migration (and thereby migrant fatalities) by altering the decision calculus associated with the journey. We here investigate this ‘pull factor’ claim by focusing on the Central Mediterranean route, the most frequented and deadly irregular migration route towards Europe during the past decade. Based on three intervention periods—(1) state-led Mare Nostrum, (2) private-led search-and-rescue, and (3) coordinated pushbacks by the Libyan Coast Guard—which correspond to substantial changes in laws, policies, and practices of search-and-rescue in the Mediterranean, we are able to test the ‘pull factor’ claim by employing an innovative machine learning method in combination with causal inference. We employ a Bayesian structural time-series model to estimate the effects of these three intervention periods on the migration flow as measured by crossing attempts (i.e., time-series aggregate counts of arrivals, pushbacks, and deaths), adjusting for various known drivers of irregular migration. We combine multiple sources of traditional and non-traditional data to build a synthetic, predicted counterfactual flow. Results show that our predictive modeling approach accurately captures the behavior of the target time-series during the various pre-intervention periods of interest. A comparison of the observed and predicted counterfactual time-series in the post-intervention periods suggest that pushback policies did affect the migration flow, but that the search-and-rescue periods did not yield a discernible difference between the observed and the predicted counterfactual number of crossing attempts. Hence we do not find support for search-and-rescue as a driver of irregular migration. In general, this modeling approach lends itself to forecasting migration flows with the goal of answering causal queries in migration research.