Effective Viscous Damping Enables Morphological Computation in Legged Locomotion

Muscle models and animal observations suggest that physical damping is beneficial for stabilization. Still, only a few implementations of mechanical damping exist in compliant robotic legged locomotion. It remains unclear how physical damping can be exploited for locomotion tasks, while its advantages as sensor-free, adaptive force- and negative work-producing actuators are promising. In a simplified numerical leg model, we studied the energy dissipation from viscous and Coulomb damping during vertical drops with ground-level perturbations. A parallel spring-damper is engaged between touch-down and mid-stance, and its damper auto-disengages during mid-stance and takeoff. Our simulations indicate that an adjustable and viscous damper is desired. In hardware we explored effective viscous damping and adjustability and quantified the dissipated energy. We tested two mechanical, leg-mounted damping mechanisms; a commercial hydraulic damper, and a custom-made pneumatic damper. The pneumatic damper exploits a rolling diaphragm with an adjustable orifice, minimizing Coulomb damping effects while permitting adjustable resistance. Experimental results show that the leg-mounted, hydraulic damper exhibits the most effective viscous damping. Adjusting the orifice setting did not result in substantial changes of dissipated energy per drop, unlike adjusting damping parameters in the numerical model. Consequently, we also emphasize the importance of characterizing physical dampers during real legged impacts to evaluate their effectiveness for compliant legged locomotion

Tunable Mechanical Damping in Fast Perturbed Locomotion: Biomechanical Simulations and Biorobotic Applications

Legged animals show extraordinary versatility in navigating complex environments and overcoming unexpected obstacles. This agility appears promoted by mechanical compliance intrinsic to their limbs. Extensive research has been conducted on the importance of elastic compliance for legged locomotion, demonstrating numerous benefits such as improved energy efficiency, enhanced shock absorption, and facilitated power generation. However, elastic compliance can also produce unwanted vibrations, reduce control bandwidth, and cannot counter energy disturbances. Although rarely implemented in legged robotics, mechanical damping is a promising solution to these limitations. Interestingly, muscle fibers exhibit viscous-like damping behavior when suddenly stretched. This capacity seems dependent on muscle excitation level, indicating that tunable mechanical damping plays a functional role in biological locomotion. In particular, tunable mechanical damping could facilitate a quick response to sudden perturbations, mitigating errors and delays in sensorimotor information. This doctoral dissertation investigates principles of tunable mechanical damping in fast perturbed legged-locomotion. Through quantitative methodologies, it expands previous knowledge of how muscle fibers exploit tunable mechanical damping around touchdown. Central to this research was the force-velocity relation, a phenomenological function describing viscous-like capacities within muscle contraction dynamics. Additionally, this thesis explores technical solutions to achieve tunable mechanical damping in legged robotics, combining numerical analysis and hardware experiments. The content of this dissertation relies on five manuscripts (four peer-reviewed journal articles and a pre-print), the fruit of collaborative research during my doctoral project. In two computational studies, we could confirm that the force-velocity relation grants muscle fibers tunable mechanical damping during the earliest response to step perturbations (i.e., the preflex phase). However, we found that current interpretations of this phenomenon require revision. Without feedforward neuronal modulation, muscle-produced mechanical damping played a minor contribution in regulating the preflex response. Large impact velocities during reference hopping could further compromise such contribution. In contrast, tunable mechanical damping produced by the force-velocity relation became a dominant regulating factor when feedforward stimulation was allowed. In particular, we observed more adjustment of touchdown force and preflex work in response to step perturbations and a simultaneous increase in hopping stability. Since our computational studies relied on Hill-type muscle models, which are ansatz approximations of real muscle contraction, we conducted an in vitro investigation with realistic boundary conditions to validate our simulations. This study confirmed activity-dependent damping-like properties in biological muscle fibers. However, the results showed an initial short-range stiffness phase, which Hill-type models should include for better predictions. In vitro, the muscle fibers' viscous-like response developed more smoothly and later than what was observed in our simulations, suggesting the need for a better characterization of the force-velocity relation's eccentric side. Inspired by the biological observations of viscous-like properties within the muscle fibers, we investigated the advantages of incorporating viscous dampers to provide tunable mechanical damping in legged robots. Using numerical simulations of a robotic leg, we found that viscous damping consistently outperforms Coulomb friction damping in rejecting potential energy disturbances caused by step perturbations. In contrast, our empirical hardware experiments revealed that damping rate control of a viscous damper that is directly connected to the knee joint fails to generate mechanical damping that can be fine-tuned. In a follow-up study, we overcame this limitation with a slack-damper mechanism. This device uses a cable with adjustable slackness to connect the viscous damper to the knee rotation. Using hopping experiments with various terrain disturbances, we demonstrate that slackness control could effectively and intuitively adjust energy dissipation in a leg prototype, indicating that tunable mechanical damping was achieved. These experiments also confirmed that embedded mechanical damping causes a trade-off between locomotion energy efficiency and robustness. We argue that the tunability of our slack-damper mechanism and its perturbation-triggered nature make this trade-off more favorable. The findings of this dissertation support previous evidence that tunable mechanical damping is beneficial for legged locomotion. We demonstrate that tunable mechanical damping can naturally occur in biological systems due to an intricate interaction between neuromodulation, inner muscle mechanics, and environmental conditions. In legged robotics, our slack-damper mechanism shows that simple technical solutions are sufficient to implement tunable mechanical damping effectively

Slack tendon enables tunable damping for legged locomotion

The 11th International Symposium on Adaptive Motion of Animals and Machines. Kobe University, Japan. 2023-06-06/09. Adaptive Motion of Animals and Machines Organizing Committee.Poster Session P

Muscle preflex response to perturbations in locomotion: In vitro experiments and simulations with realistic boundary conditions

Neuromuscular control loops feature substantial communication delays, but mammals run robustly even in the most adverse conditions. In vivo experiments and computer simulation results suggest that muscles’ preflex—an immediate mechanical response to a perturbation—could be the critical contributor. Muscle preflexes act within a few milliseconds, an order of magnitude faster than neural reflexes. Their short-lasting action makes mechanical preflexes hard to quantify in vivo. Muscle models, on the other hand, require further improvement of their prediction accuracy during the non-standard conditions of perturbed locomotion. Our study aims to quantify the mechanical work done by muscles during the preflex phase (preflex work) and test their mechanical force modulation. We performed in vitro experiments with biological muscle fibers under physiological boundary conditions, which we determined in computer simulations of perturbed hopping. Our findings show that muscles initially resist impacts with a stereotypical stiffness response—identified as short-range stiffness—regardless of the exact perturbation condition. We then observe a velocity adaptation to the force related to the amount of perturbation similar to a damping response. The main contributor to the preflex work modulation is not the change in force due to a change in fiber stretch velocity (fiber damping characteristics) but the change in magnitude of the stretch due to the leg dynamics in the perturbed conditions. Our results confirm previous findings that muscle stiffness is activity-dependent and show that also damping characteristics are activity-dependent. These results indicate that neural control could tune the preflex properties of muscles in expectation of ground conditions leading to previously inexplicable neuromuscular adaptation speeds

Muscle preflex response to perturbations in locomotion : in vitro experiments and simulations with realistic boundary conditions

Neuromuscular control loops feature substantial communication delays, but mammals run robustly even in the most adverse conditions. In vivo experiments and computer simulation results suggest that muscles’ preflex - an immediate mechanical response to a perturbation - could be the critical contributor. Muscle preflexes act within a few milliseconds, an order of magnitude faster than neural reflexes. Their short-lasting action makes mechanical preflexes hard to quantify in vivo. Muscle models, on the other hand, require further improvement of their prediction accuracy during the non-standard conditions of perturbed locomotion. Our study aims to quantify the mechanical work done by muscles during the preflex phase (preflex work) and test their mechanical force modulation. We performed in vitro experiments with biological muscle fibers under physiological boundary conditions, which we determined in computer simulations of perturbed hopping. Our findings show that muscles initially resist impacts with a stereotypical stiffness response - identified as short-range stiffness - regardless of the exact perturbation condition. We then observe a velocity adaptation to the force related to the amount of perturbation similar to a damping response. The main contributor to the preflex work modulation is not the change in force due to a change in fiber stretch velocity (fiber damping characteristics) but the change in magnitude of the stretch due to the leg dynamics in the perturbed conditions. Our results confirm previous findings that muscle stiffness is activity-dependent and show that also damping characteristics are activity-dependent. These results indicate that neural control could tune the preflex properties of muscles in expectation of ground conditions leading to previously inexplicable neuromuscular adaptation speeds.Deutsche Forschungsgemeinschaf

A new case report of severe mucopolysaccharidosis type VII: diagnosis, treatment with haematopoietic cell transplantation and prenatal diagnosis in a second pregnancy

A new patient with severe mucopolysaccharidosis (MPS) type VII is reported. Non-immune hydrops fetalis (NIHF) was diagnosed during pregnancy. At birth, he showed generalized hydrops and dysmorphic features typical of MPS. Many diagnoses were excluded before reaching the diagnosis of MPS VII at 8 months of life. During the first year of life he had frequent respiratory infections associated with restrictive and obstructive bronchopneumopathy and underwent three surgical interventions: decompression of the spinal cord at the craniocervical junction, bilateral inguinal hernia, and bilateral clubfoot. At 14 months of life he underwent successful haematopoietic cell transplantation (HCT). During the following 10 months, his bronchopneumopathy progressively worsened, needing chronic pharmacological treatment and O2 administration. The patient died of respiratory insufficiency during a respiratory syncytial virus infection at 25 months of age. Molecular analysis showed the homozygous variant c.1617C > T, leading to the synonymous mutation p.Ser539=. This caused aberrant splicing with partial skipping of exon 10 (r.1616_1653del38) and complete skipping of exon 9 (r.1392_1476del85; r.1616_1653del38). No transcript of normal size was evident. The parents were both confirmed to be carriers. In a subsequent pregnancy, a prenatal diagnosis showed an affected fetus. Ultrasound examination before abortion showed NIHF. The skin and placenta examination by electron microscopy showed foamy intracytoplasmic vacuoles with a weakly electron-dense substrate. MPS VII is a very rare disease but it is possible that some cases go undiagnosed for several reasons, including that MPS VII, and other lysosomal storage diseases, are not included in the work-up for NIHF in many institutions, and the presence of anasarca at birth may be confounding for the recognition of the typical facial characteristics of the disease. This is the eighth patient affected by MPS VII who has undergone HCT. It is not possible to draw conclusions about the efficacy of HCT in MPS VII. Treatment with enzyme replacement is now available and will probably be beneficial for the patients who have a milder form with no or little cognitive involvement. Increased awareness among clinicians is needed for prompt diagnosis and to offer the correct treatment as early as possible

Clinical characteristics of a large cohort of patients with narcolepsy candidate for pitolisant: a cross-sectional study from the Italian PASS Wakix® Cohort

Introduction Narcolepsy is a chronic and rare hypersomnia of central origin characterized by excessive daytime sleepiness and a complex array of symptoms as well as by several medical comorbidities. With growing pharmacological options, polytherapy may increase the possibility of a patient-centered management of narcolepsy symptoms. The aims of our study are to describe a large cohort of Italian patients with narcolepsy who were candidates for pitolisant treatment and to compare patients' subgroups based on current drug prescription (drug-naive patients in whom pitolisant was the first-choice treatment, switching to pitolisant from other monotherapy treatments, and adding on in polytherapy). Methods We conducted a cross-sectional survey based on Italian data from the inclusion visits of the Post Authorization Safety Study of pitolisant, a 5-year observational, multicenter, international study. Results One hundred ninety-one patients were enrolled (76.4% with narcolepsy type 1 and 23.6% with narcolepsy type 2). Most patients (63.4%) presented at least one comorbidity, mainly cardiovascular and psychiatric. Pitolisant was prescribed as an add-on treatment in 120/191 patients (62.8%), as switch from other therapies in 42/191 (22.0%), and as a first-line treatment in 29/191 (15.2%). Drug-naive patients presented more severe sleepiness, lower functional status, and a higher incidence of depressive symptoms. Conclusion Our study presents the picture of a large cohort of Italian patients with narcolepsy who were prescribed with pitolisant, suggesting that polytherapy is highly frequent to tailor a patient-centered approach

Brivaracetam as Early Add-On Treatment in Patients with Focal Seizures: A Retrospective, Multicenter, Real-World Study

Introduction In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Most real-world research on BRV has focused on refractory epilepsy. The aim of this analysis was to assess the 12-month effectiveness and tolerability of adjunctive BRV when used as early or late adjunctive treatment in patients included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). Methods BRIVAFIRST was a 12-month retrospective, multicenter study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of sustained seizure response, sustained seizure freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events (AEs) and the incidence of AEs. Data were compared for patients treated with add-on BRV after 1-2 (early add-on) and >= 3 (late add-on) prior antiseizure medications. Results A total of 1029 patients with focal epilepsy were included in the study, of whom 176 (17.1%) received BRV as early add-on treatment. The median daily dose of BRV at 12 months was 125 (100-200) mg in the early add-on group and 200 (100-200) in the late add-on group (p < 0.001). Sustained seizure response was reached by 97/161 (60.3%) of patients in the early add-on group and 286/833 (34.3%) of patients in the late add-on group (p < 0.001). Sustained seizure freedom was achieved by 51/161 (31.7%) of patients in the early add-on group and 91/833 (10.9%) of patients in the late add-on group (p < 0.001). During the 1-year study period, 29 (16.5%) patients in the early add-on group and 241 (28.3%) in the late add-on group discontinued BRV (p = 0.001). Adverse events were reported by 38.7% and 28.5% (p = 0.017) of patients who received BRV as early and late add-on treatment, respectively. Conclusion Brivaracetam was effective and well tolerated both as first add-on and late adjunctive treatment in patients with focal epilepsy

The genetic study of three population microisolates in South Tyrol (MICROS): study design and epidemiological perspectives

<p>Abstract</p> <p>Background</p> <p>There is increasing evidence of the important role that small, isolated populations could play in finding genes involved in the etiology of diseases. For historical and political reasons, South Tyrol, the northern most Italian region, includes several villages of small dimensions which remained isolated over the centuries.</p> <p>Methods</p> <p>The MICROS study is a population-based survey on three small, isolated villages, characterized by: old settlement; small number of founders; high endogamy rates; slow/null population expansion. During the stage-1 (2002/03) genealogical data, screening questionnaires, clinical measurements, blood and urine samples, and DNA were collected for 1175 adult volunteers. Stage-2, concerning trait diagnoses, linkage analysis and association studies, is ongoing. The selection of the traits is being driven by expert clinicians. Preliminary, descriptive statistics were obtained. Power simulations for finding linkage on a quantitative trait locus (QTL) were undertaken.</p> <p>Results</p> <p>Starting from participants, genealogies were reconstructed for 50,037 subjects, going back to the early 1600s. Within the last five generations, subjects were clustered in one pedigree of 7049 subjects plus 178 smaller pedigrees (3 to 85 subjects each). A significant probability of familial clustering was assessed for many traits, especially among the cardiovascular, neurological and respiratory traits. Simulations showed that the MICROS pedigree has a substantial power to detect a LOD score ≥ 3 when the QTL specific heritability is ≥ 20%.</p> <p>Conclusion</p> <p>The MICROS study is an extensive, ongoing, two-stage survey aimed at characterizing the genetic epidemiology of Mendelian and complex diseases. Our approach, involving different scientific disciplines, is an advantageous strategy to define and to study population isolates. The isolation of the Alpine populations, together with the extensive data collected so far, make the MICROS study a powerful resource for the study of diseases in many fields of medicine. Recent successes and simulation studies give us confidence that our pedigrees can be valuable both in finding new candidates loci and to confirm existing candidate genes.</p