Can kinematic parameters of 3D reach-to-target movements be used as a proxy for clinical outcome measures in chronic stroke rehabilitation? An exploratory study.

BACKGROUND: Despite numerous trials investigating robot-assisted therapy (RT) effects on upper-extremity (UE) function after stroke, few have explored the relationship between three-dimensional (3D) reach-to-target kinematics and clinical outcomes. The objectives of this study were to 1) investigate the correlation between kinematic parameters of 3D reach-to-target movements and UE clinical outcome measures, and 2) examine the degree to which differences in kinematic parameters across individuals can account for differences in clinical outcomes in response to RT. METHODS: Ten chronic stroke survivors participated in a pilot RT intervention (eighteen 1-h sessions) integrating cognitive skills training and a home-action program. Clinical outcome measures and kinematic parameters of 3D reach-to-target movements were collected pre- and post-intervention. The correlation between clinical outcomes and kinematic parameters was investigated both cross-sectionally and longitudinally (i.e., changes in response to the intervention). Changes in clinical outcomes and kinematic parameters were tested for significance in both group and subject-by-subject analyses. Potential associations between individual differences in kinematic parameters and differences in clinical outcomes were examined. RESULTS: Moderate-to-strong correlation was found between clinical measures and specific kinematic parameters when examined cross-sectionally. Weaker correlation coefficients were found longitudinally. Group analyses revealed significant changes in clinical outcome measures in response to the intervention; no significant group changes were observed in kinematic parameters. Subject-by-subject analyses revealed changes with moderate-to-large effect size in the kinematics of 3D reach-to-target movements pre- vs. post-intervention. Changes in clinical outcomes and kinematic parameters varied widely across participants. CONCLUSIONS: Large variability was observed across subjects in response to the intervention. The correlation between changes in kinematic parameters and clinical outcomes in response to the intervention was variable and not strong across parameters, suggesting no consistent change in UE motor strategies across participants. These results highlight the need to investigate the response to interventions at the individual level. This would enable the identification of clusters of individuals with common patterns of change in response to an intervention, providing an opportunity to use cluster-specific kinematic parameters as a proxy of clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02747433 . Registered on April 21st, 2016.

Autonomous multi-joint soft exosuit with augmentation-power-based control parameter tuning reduces energy cost of loaded walking.

BACKGROUND: Soft exosuits are a recent approach for assisting human locomotion, which apply assistive torques to the wearer through functional apparel. Over the past few years, there has been growing recognition of the importance of control individualization for such gait assistive devices to maximize benefit to the wearer. In this paper, we present an updated version of autonomous multi-joint soft exosuit, including an online parameter tuning method that customizes control parameters for each individual based on positive ankle augmentation power. METHODS: The soft exosuit is designed to assist with plantarflexion, hip flexion, and hip extension while walking. A mobile actuation system is mounted on a military rucksack, and forces generated by the actuation system are transmitted via Bowden cables to the exosuit. The controller performs an iterative force-based position control of the Bowden cables on a step-by-step basis, delivering multi-articular (plantarflexion and hip flexion) assistance during push-off and hip extension assistance in early stance. To individualize the multi-articular assistance, an online parameter tuning method was developed that customizes two control parameters to maximize the positive augmentation power delivered to the ankle. To investigate the metabolic efficacy of the exosuit with wearer-specific parameters, human subject testing was conducted involving walking on a treadmill at 1.50 m s- 1 carrying a 6.8-kg loaded rucksack. Seven participants underwent the tuning process, and the metabolic cost of loaded walking was measured with and without wearing the exosuit using the individualized control parameters. RESULTS: The online parameter tuning method was capable of customizing the control parameters, creating a positive ankle augmentation power map for each individual. The subject-specific control parameters and resultant assistance profile shapes varied across the study participants. The exosuit with the wearer-specific parameters significantly reduced the metabolic cost of load carriage by 14.88 ± 1.09% (P = 5 × 10- 5) compared to walking without wearing the device and by 22.03 ± 2.23% (P = 2 × 10- 5) compared to walking with the device unpowered. CONCLUSION: The autonomous multi-joint soft exosuit with subject-specific control parameters tuned based on positive ankle augmentation power demonstrated the ability to improve human walking economy. Future studies will further investigate the effect of the augmentation-power-based control parameter tuning on wearer biomechanics and energetics.

Kinetic and Thermodynamic Stabilization of Metal Complexes by Introverted Coordination in a Calix[6]azacryptand.

The Huisgen thermal reaction between an organic azide and an acetylene was employed for the selective monofunctionalization of a X6 -azacryptand ligand bearing a tren coordinating unit [X6 stands for calix[6]arene and tren for tris(2-aminoethyl)amine]. Supramolecular assistance, originating from the formation of a host-guest inclusion complex between the reactants, greatly accelerates the reaction while self-inhibition affords a remarkable selectivity. The new ligand possesses a single amino-leg appended at the large rim of the calixarene core and the corresponding Zn(2+) complex was characterized both in solution and in the solid state. The coordination of Zn(2+) not only involves the tren cap but also the introverted amino-leg, which locks the metal ion in the cavity. Compared with the parent ligand deprived of the amino-leg, the affinity of the new monofunctionalized X6 tren ligand 6 for Zn(2+) is found to have a 10-fold increase in DMSO, which is a very competitive solvent, and with an enhancement of at least three orders of magnitude in CDCl3 /CD3 OD (1:1, v/v). In strong contrast with the fast binding kinetics, decoordination of Zn(2+) as well as transmetallation appeared to be very slow processes. The monofunctionalized X6 tren ligand 6 fully protects the metal ion from the external medium thanks to the combination of a cavity and a closed coordination sphere, leading to greater thermodynamic and kinetic stabilities.

Guest covalent capture by a host: a biomimetic strategy for the selective functionalization of a cavity.

A biomimetic strategy for the monofunctionalization of a calix[6]arene core is described. It is based on host-guest chemistry (mimicking the Michaelis-Menten adduct in enzymes) and allows the finely tuned pre-organization of the substrate (an alkyne) with respect to the reactant (three azido groups introduced at the calixarene large rim). It is shown that the thermal Huisgen reaction implemented in this work proceeds under very mild conditions with total regioselectivity of the cycloaddition process. The scope of the reaction was explored and the results suggest that such a supramolecular strategy is quite versatile and could be applied to the selective functionalization of other cavitands bearing different recognition patterns. A detailed structural, thermodynamic, and kinetic study is also reported, highlighting interesting biomimetic features: The importance of the host-guest adduct strength, the high sensitivity of the reaction to the pre-organization of the reactive partners (alkyne vs. azide), and a significant impact of the embedment on the transition state. The self-coordination of the monofunctionalized products was also studied and an "endo/exo" switch of the internal side-chain could be triggered by adding competitive ligands.

Electrochemically driven cup-and-ball CuI and CuII complexes.

The conformation of copper "funnel" complexes that contains a coordinating appended arm can be electrochemically switched between endo, which corresponds to the self-coordination of the arm through the cavity, and exo positions. This process, which is reminiscent of a cup-and-ball device, is activated by an exogenous ligand for complexes that contain a hydroxy-terminated arm. The exchange is electrochemically triggered and is operated in either Cu(I) or Cu(II) redox states, depending on the exogenous ligand, that is, CO or n-butylamine, respectively.

Guest-triggered Zn(II) translocation and supramolecular nuclearity control in calix[6]arene-based complexes.

Two new polytopic ligands based on a calix[6]arene scaffold were synthesized. The truncated cone-shaped calixarene was functionalized at its small rim by a tris-imidazole site, aimed at generating a tetrahedral Zn(II) complex, where a fourth labile site inside the cavity is accessible through the funnel provided by its large rim. Tridentate aza ligands (either two or three) were then grafted at this large rim (the entrance of the cavity). Zn(II) coordination studies, monitored by (1)H NMR spectroscopy, showed unprecedented behavior in this family of heteropolytopic ligands. Indeed, it gives access to complexes of various nuclearities in acetonitrile, where zinc binding is under the supramolecular control of the guest. It is first shown that, in the absence of a good guest donor (a primary amine), Zn(II) binding is favored at the large rim where two tridentate nitrogenous groups can form an octahedral complex. The addition of a long guest such as heptylamine induces the quantitative translocation of the Zn(II) ion from the large rim octahedral (O(h)) site to the small rim tetrahedral (T(d)) site provided by the trisimidazole core and the guest ligand. With 2 equiv of Zn(II), well-defined dinuclear complexes were obtained and isolated, with one Zn(II) ion bound at each rim. Interestingly, it is shown that the binding mode at the large rim is under the supramolecular control of the guest bound at the small rim (with short guests, the O(h) environment is obtained at the large rim, whereas long guests disrupt this core through an induced-fit process); the partially included and dangling alkyl chain opens the large rim (entrance of the cavity) and pushes apart the tridentate moieties. As a result, a guest-induced switch of Zn(II) binding mode occurs and frees one of the tridentate groups from coordination, allowing further extension of the complex nuclearity.

Reducing the metabolic rate of walking and running with a versatile, portable exosuit.

Walking and running have fundamentally different biomechanics, which makes developing devices that assist both gaits challenging. We show that a portable exosuit that assists hip extension can reduce the metabolic rate of treadmill walking at 1.5 meters per second by 9.3% and that of running at 2.5 meters per second by 4.0% compared with locomotion without the exosuit. These reduction magnitudes are comparable to the effects of taking off 7.4 and 5.7 kilograms during walking and running, respectively, and are in a range that has shown meaningful athletic performance changes. The exosuit automatically switches between actuation profiles for both gaits, on the basis of estimated potential energy fluctuations of the wearer's center of mass. Single-participant experiments show that it is possible to reduce metabolic rates of different running speeds and uphill walking, further demonstrating the exosuit's versatility.