Lower-Limb Exosuits for Rehabilitation or Assistance of Human Movement: A Systematic Review

Background: The aim of this review is to provide a comprehensive overview of the technological state-of-the-art of exosuits and the clinical results obtained when applied to users with mobility impairment. Methods: Searches are carried out in the COCHRANE, PubMed, IEEE Xplore and MEDLINE databases. Titles, abstracts and full texts are screened for inclusion criteria. Technological and clinical data are extracted. The quality of the studies is evaluated via a study quality assessment tool. Results: 19 studies are identified as relevant. Active (47%) and passive exosuits (53%) are used. Most are used untethered (84%), accommodating the demand of mobility. No study reports power consumption, which is important for dimensioning power systems. Fields of applications are post-stroke (79%), osteoarthritis (16%) and post-trauma (5%). Mostly the ankle joint is addressed (57%), while less studies address multiple joints (21%). The outcomes of clinical evaluations of lower-limb exosuits with patients suffering from mobility impairments are positive in the correction of gait pattern and reducing metabolic energy consumption during hemiparetic walking. Conclusions: Lower-limb exosuits for clinical applications are still facing technological challenges. Fields of application are limited to stroke, osteoarthritis and trauma. While clinical outcomes are overall positive, improvements in the study protocols are suggested.Peer ReviewedObjectius de Desenvolupament Sostenible::3 - Salut i BenestarPostprint (published version

Development of in vitro and in vivo Bioreactors for Bone Tissue Engineering

Grandes defectos óseos constituyen un reto para el campo clínico, ya que no puede ser reparado por el propio organismo, sino que requieren la implantación de injertos de hueso adecuado. Para superar los inconvenientes de los injertos procedentes de fuentes autólogas o allogeneicas, la ingeniería de tejidos óseos pretende sustituir el tejido perdido utilizando el cultivo de células in vitro sobre biomateriales porosos. El cultivo de células en grandes andamios porosos ha demostrado ser difícil, que requiere bioreactores, que se utilizan para el cultivo de tejidos y el estudio del comportamiento de células en 3D de los andamios. De interés especial es el condicionamiento mecánico de los tejidos cultivados por bioreactor de la ingeniería del tejido óseo, que es capaz de aumentar el potencial osteogénico de los injertos sintéticos.En este trabajo, dos sistemas de bioreactores fueron desarrollados para permitir comprender las propiedades bioactivas de andamios de diferentes materiales y la mecanoregulación del comportamiento de células o tejidos. Un sistema de bioreactor de perfusión in vitro fue desarrollado para el sembrado y cultivo de células incorporadas en cilindros de un biomaterial poroso. Varios estudios para la determinación de los parámetros del sembrado de células aplicable se llevaron a cabo, así como experimentos de cultivo de células bajo flujo de fluido constante con una estimulación mecánica adicional por alternancia del flujo.Un sistema de cámara ósea fue desarrollado como un bioreactor in vivo. El sistema produjo un defecto óseo grande en tibias de perros y permitió la implantación repetida de grandes andamios porosos de materiales diferentes. El tejido creciendo en los andamios permite extraer conclusiones sobre las propiedades de osteoconductividad u osteinductividad de los andamios. Además, un dispositivo de compresión se ha desarrollado para aplicar cargas cíclicas en los andamios en vivo para estudiar el efecto de la estimulación mecánica en el desarrollo de los tejidos.Los estudios con el sistema de perfusión desarrollado han demostrado que el sembrado de células en grandes andamios porosos es posible, lo que se considera crucial para el cultivo celular. El largo tiempo de cultivo de células mostró la proliferación de las células madre mesenquimales hasta dos semanas. El patrón de estimulación utilizado en el estudio aumentó la expresión de la osteocalcina, lo que indica una mayor actividad de las células, pero la ausencia de expresión de RunX2 y colágeno I impidió la determinación concluyente de la diferenciación.El sistema desarrollado de la cámara ósea demostró su funcionalidad en el entorno quirúrgico durante los experimentos in vivo. Complicaciones durante los experimentos no permitieron la aplicación de las cargas cíclicas de los andamios implantados. La formación de hueso retrasada debido al defecto óseo creado y material de andamios restantes no permitieron conclusiones definitivas acerca de las propiedades del material del andamio. Sin embargo, el estudio proporciona datos para el desarrollo futuro del dispositivo y protocolo clínico.Los estudios realizados constituyen una novedad en respecto a la creación de bioreactores para el estudio de la andamios porosos sintéticos de grandes dimensiones in vitro e in vivo. Los sistemas desarrollados constituyen la base para otros estudios en mecanobiología de las células óseas y los tejidos.Large bone defects constitute a challenge for the clinical field, because they cannot be repaired by the body itself, but require the implantation of suitable bone grafts. To overcome the drawbacks of grafts from autologous or allogous sources, modern bone tissue engineering aims to replace lost tissue by cultivating cells in vitro on porous biomaterials. The cell culture on large porous scaffolds has shown to be difficult, requiring bioreactors, which are used for tissue culture and the study of cell behaviour in 3D scaffolds. Of special interest is the mechanical conditioning of the cultured tissue for bioreactor-based bone tissue engineering, which is able to enhance the osteogenic potential of the synthetic grafts.In this work two bioreactor systems were developed to allow insight into bioactive properties of different scaffold materials and the mechanoregulation of cell or tissue behaviour. An in vitro perfusion bioreactor system was developed for the cell seeding and culture on porous biomaterial cylinders. Several studies for the determination of applicable cell seeding parameters were conducted, as well as experiments of cell culture under steady fluid flow with additional mechanical stimulation by alternating fluid flow. A bone chamber system was developed as an in vivo bioreactor. The system produced a large bone defect in dog tibia and allowed the repeated implantation of large porous scaffolds of different material compositions.The ingrowing tissue was observed to allow conclusions about osteoconductive or osteinductive properties of the scaffolds. Additionally a compression device was developed to apply cyclic loading on the scaffolds in vivo to study the effect of mechanical stimulation on tissue development.The studies with the developed in vitro perfusion bioreactor system have shown that it is possible to seed cells throughout large porous scaffolds, which is deemed crucial for the further cell culture. The long time cell culture showed the proliferation of mesenchymal stem cells up to two weeks. The stimulation pattern used in the study enhanced the expression of osteocalcin, indicating an enhanced cell activity, but the absence of RunX2 and collagen I expression rendered the determination of differentiation inconclusive.The developed bone chamber system proved to be functional in the surgical environment during the in vivo experiments. Occurring complications during the experiments did not allow the application of the cyclic loading of implanted scaffolds. Delayed bone formation due to created bone defect and remaining scaffold material did not allow final conclusions about the scaffold material properties. Nevertheless the study provides input for further development of the device and clinical protocol.The conducted studies constitute a novelty regarding the creation of bioreactors for the study of synthetic porous scaffolds of large dimensions in vitro and in vivo. The developed systems form the basis for further studies in mechanobiology of bone cells and tissue

The Highly Unusual Chemical Composition of the Hercules Dwarf Spheroidal Galaxy

We report on the abundance analysis of two red giants in the faint Hercules dwarf spheroidal (dSph) galaxy. These stars show a remarkable deficiency in the neutron-capture elements, while the hydrostatic alpha-elements (O, Mg) are strongly enhanced. Our data indicate [Ba/Fe] and [Mg/Fe] abundance ratios of <-2 dex and ~+0.8 dex, respectively, with essentially no detection of other n-capture elements. In contrast to the only other dSph star with similar abundance patterns, Dra 119, which has a very low metallicity at [Fe/H]=-2.95 dex, our objects, at [Fe/H]~-2.0 dex, are only moderately metal poor. The measured ratio of hydrostatic/explosive alpha-elements indicates that high-mass (~35 M_sun) Type II supernovae progenitors are the main, if not only, contributors to the enrichment of this galaxy. This suggests that star formation and chemical enrichment in the ultrafaint dSphs proceeds stochastically and inhomogeneously on small scales, or that the IMF was strongly skewed to high mass stars. The neutron capture deficiencies and the [Co/Fe] and [Cr/Fe] abundance ratios in our stars are similar to those in the extremely low metallicity Galactic halo. This suggests that either our stars are composed mainly of the ejecta from the first, massive, population III stars (but at moderately high [Fe/H]), or that SN ejecta in the Hercules galaxy were diluted with ~30 times less hydrogen than typical for extreme metal-poor stars.Comment: 5 pages, 3 figures, accepted by Astrophysical Journal Letter

Real-Time Message Routing and Scheduling

Exchanging messages between nodes of a network (e.g., embedded computers) is a fundamental issue in real-time systems involving critical routing and scheduling decisions. In order for messages to meet their deadlines, one has to determine a suitable (short) origin-destination path for each message and resolve conflicts between messages whose paths share a communication link of the network. With this paper we contribute to the theoretic foundations of real-time systems. On the one hand, we provide efficient routing strategies yielding origin-destination paths of bounded dilation and congestion. In particular, we can give good a priori guarantees on the time required to send a given set of messages which, under certain reasonable conditions, implies that all messages can be scheduled to reach their destination on time. Finally, for message routing along a directed path (which is already NP-hard), we identify a natural class of instances for which a simple scheduling heuristic yields provably optimal solutions

Host-specific symbiotic requirement of BdeAB, a RegR-controlled RND-type efflux system in Bradyrhizobium japonicum

Multidrug efflux systems not only cause resistance against antibiotics and toxic compounds but also mediate successful host colonization by certain plant-associated bacteria. The genome of the nitrogen-fixing soybean symbiont Bradyrhizobium japonicum encodes 24 members of the family of resistance/nodulation/cell division (RND) multidrug efflux systems, of which BdeAB is genetically controlled by the RegSR two-component regulatory system. Phylogenetic analysis of the membrane components of these 24 RND-type transporters revealed that BdeB is more closely related to functionally characterized orthologs in other bacteria, including those associated with plants, than to any of the other 23 paralogs in B. japonicum. A mutant with a deletion of the bdeAB genes was more susceptible to inhibition by the aminoglycosides kanamycin and gentamicin than the wild type, and had a strongly decreased symbiotic nitrogen-fixation activity on soybean, but not on the alternative host plants mungbean and cowpea, and only very marginally on siratro. The host-specific role of a multidrug efflux pump is a novel feature in the rhizobia-legume symbioses. Consistent with the RegSR dependency of bdeAB, a B. japonicum regR mutant was found to have a greater sensitivity against the two tested antibiotics and a symbiotic defect that is most pronounced for soybea

A common PID Kernel Information Profile for the German Helmholtz Association of Research Centres

In the concept of FAIR Digital Objects, PID Kernel Information is key to machine actionability of digital content. Strongly relying on Data Types and stored in a PID record directly at the PID resolution service, allows PID Kernel Information to be used by machines for fast decision making. To make a first step into the direction of standardizing PID Kernel Information, the RDA Working Group on PID Kernel Information has defined a first proposal of a core Kernel Information Profile (KIP) together with a list of seven guiding principles helping to decide on which information could be part of a KIP and which information should be stored elsewhere. The Helmholtz Metadata Collaboration (HMC) Platform is a joint endeavor across all research areas of the Helmholtz Association, the largest association of large-scale research centers in Germany. The goal of HMC is to make the depth and breadth of research data produced by Helmholtz Centres findable, accessible, interoperable, and reusable (FAIR) for the whole science community. To reach this goal, the concept of FAIR Digital Objects has been chosen as top-level commonality across all research fields and their existing and future infrastructures. In order to fulfill this role, a common Helmholtz KIP has been agreed on serving as basis for all FAIR Digital Objects created in the context of HMC. This poster describes the Helmholtz KIP and elaborates on decisions leading to differences compared to the core KIP recommended by the RDA. While remaining mostly compatible to the RDA core KIP, the Helmholtz KIP adds some additional properties that satisfy the multidisciplinary environment it is made for. Thus, it serves as a good starting point for rolling out the FAIR Digital Object concept over all Research Data Management Infrastructures of the Helmholtz Association and beyond. In addition, the poster provides a first impression of a demonstrator, which is currently under development and should serve as showcase. In the first step, we will allow to transform arbitrary datasets from Zenodo into FAIR Digital Objects using our Helmholtz KIP. In a next step, we plan to also include datasets from infrastructures hosted at Helmholtz Centres to create a huge and unprecedented network of FAIR Digital Objects, which provides scientists with an incredible pool of linked and searchable research data. This work has been supported by the research program ‘Engineering Digital Futures’ of the Helmholtz Association of German Research Centers and the Helmholtz Metadata Collaboration Platform

A basic Helmholtz Kernel Information Profile for machine-actionable FAIR Digital Objects

To reach the declared goal of the Helmholtz Metadata Collaboration Platform, making the depth and breadth of research data produced by Helmholtz Centres findable, accessible, interoperable, and reusable (FAIR) for the whole science community, the concept of FAIR Digital Objects (FAIR DOs) has been chosen as top-level commonality across all research fields and their existing and future infrastructures. Over the last years, not only by the Helmholtz Metadata Collaboration Platform, but on an international level, the roads towards realizing FAIR DOs has been paved more and more by concretizing concepts and implementing base services required for realizing FAIR DOs, e.g., different instances of Data Type Registries for accessing, creating, and managing Data Types required by FAIR DOs and technical components to support the creation and management of FAIR DOs: The Typed PID Maker providing machine actionable interfaces for creating, validating, and managing PIDs with machine-actionable metadata stored in their PID record, or the FAIR DO testbed, currently evolving into the FAIR DO Lab, serving as reference implementation for setting up a FAIR DO ecosystem. However, introducing FAIR DOs is not only about providing technical services, but also requires the definition and agreement on interfaces, policies, and processes. A first step in this direction was made in the context of HMC by agreeing on a Helmholtz Kernel Information Profile. In the concept of FAIR DOs, PID Kernel Information is key to machine actionability of digital content. Strongly relying on Data Types and stored in the PID record directly at the PID resolution service, PID Kernel Information is allowed to be used by machines for fast decision making. In this session, we will shortly present the Helmholtz Kernel Information Profile and a first demonstrator allowing the semi-automatic creation of FAIR DOs for arbitrary DOIs accessible via the well-known Zenodo repository

The masses of Local Group dwarf spheroidal galaxies: The death of the universal mass profile

We investigate the claim that all dwarf spheroidal galaxies (dSphs) reside within halos that share a common, universal mass profile as has been derived for dSphs of the Galaxy. By folding in kinematic information for 25 Andromeda dSphs, more than doubling the previous sample size, we find that a singular mass profile can not be found to fit all the observations well. Further, the best-fit dark matter density profile measured for solely the Milky Way dSphs is marginally discrepant (at just beyond the 1 sigma level) with that of the Andromeda dSphs, where a profile with lower maximum circular velocity, and hence mass, is preferred. The agreement is significantly better when three extreme Andromeda outliers, And XIX, XXI and XXV, all of which have large half-light radii (>600pc) and low velocity dispersions (sigma_v < 5km/s) are omitted from the sample. We argue that the unusual properties of these outliers are likely caused by tidal interactions with the host galaxy.Comment: ApJ in press, 16 pages, 7 figures. Updated to address referee comment

A kinematic study of the Andromeda dwarf spheroidal system

We present a homogeneous kinematic analysis of red giant branch stars within 18 of the 28 Andromeda dwarf spheroidal (dSph) galaxies, obtained using the Keck I LRIS and Keck II DEIMOS spectrographs. Based on their g-i colors (taken with the CFHT MegaCam imager), physical positions on the sky, and radial velocities, we assign probabilities of dSph membership to each observed star. Using this information, the velocity dispersions, central masses and central densities of the dark matter halos are calculated for these objects, and compared with the properties of the Milky Way dSph population. We also measure the average metallicity ([Fe/H]) from the co-added spectra of member stars for each M31 dSph and find that they are consistent with the trend of decreasing [Fe/H] with luminosity observed in the Milky Way population. We find that three of our studied M31 dSphs appear as significant outliers in terms of their central velocity dispersion, And XIX, XXI and XXV, all of which have large half-light radii (>700 pc) and low velocity dispersions (sigma_v<5 km/s). In addition, And XXV has a mass-to-light ratio within its half-light radius of just [M/L]_{half}=10.3^{+7.0}_{-6.7}, making it consistent with a simple stellar system with no appreciable dark matter component within its 1 sigma uncertainties. We suggest that the structure of the dark matter halos of these outliers have been significantly altered by tides.Comment: 41 pages, 23 figures. Accepted for publication in Ap