Context-Dependent Upper Limb Prosthesis Control for Natural and Robust Use.

Pattern recognition and regression methods applied to the surface EMG have been used for estimating the user intended motor tasks across multiple degrees of freedom (DOF), for prosthetic control. While these methods are effective in several conditions, they are still characterized by some shortcomings. In this study we propose a methodology that combines these two approaches for mutually alleviating their limitations. This resulted in a control method capable of context-dependent movement estimation that switched automatically between sequential (one DOF at a time) or simultaneous (multiple DOF) prosthesis control, based on an online estimation of signal dimensionality. The proposed method was evaluated in scenarios close to real-life situations, with the control of a physical prosthesis in applied tasks of varying difficulties. Test prostheses were individually manufactured for both able-bodied and transradial amputee subjects. With these prostheses, two amputees performed the Southampton Hand Assessment Procedure test with scores of 58 and 71 points. The five able-bodied individuals performed standardized tests, such as the box&block and clothes pin test, reducing the completion times by up to 30%, with respect to using a state-of-the-art pure sequential control algorithm. Apart from facilitating fast simultaneous movements, the proposed control scheme was also more intuitive to use, since human movements are predominated by simultaneous activations across joints. The proposed method thus represents a significant step towards intelligent, intuitive and natural control of upper limb prostheses.

A Multi-Class Proportional Myocontrol Algorithm for Upper Limb Prosthesis Control: Validation in Real-Life Scenarios on Amputees.

Functional replacement of upper limbs by means of dexterous prosthetic devices remains a technological challenge. While the mechanical design of prosthetic hands has advanced rapidly, the human-machine interfacing and the control strategies needed for the activation of multiple degrees of freedom are not reliable enough for restoring hand function successfully. Machine learning methods capable of inferring the user intent from EMG signals generated by the activation of the remnant muscles are regarded as a promising solution to this problem. However, the lack of robustness of the current methods impedes their routine clinical application. In this study, we propose a novel algorithm for controlling multiple degrees of freedom sequentially, inherently proportionally and with high robustness, allowing a good level of prosthetic hand function. The control algorithm is based on the spatial linear combinations of amplitude-related EMG signal features. The weighting coefficients in this combination are derived from the optimization criterion of the common spatial patterns filters which allow for maximal discriminability between movements. An important component of the study is the validation of the method which was performed on both able-bodied and amputee subjects who used physical prostheses with customized sockets and performed three standardized functional tests mimicking daily-life activities of varying difficulty. Moreover, the new method was compared in the same conditions with one clinical/industrial and one academic state-of-the-art method. The novel algorithm outperformed significantly the state-of-the-art techniques in both subject groups for tests that required the activation of more than one degree of freedom. Because of the evaluation in real time control on both able-bodied subjects and final users (amputees) wearing physical prostheses, the results obtained allow for the direct extrapolation of the benefits of the proposed method for the end users. In conclusion, the method proposed and validated in real-life use scenarios, allows the practical usability of multifunctional hand prostheses in an intuitive way, with significant advantages with respect to previous systems.

Self-correcting pattern recognition system of surface EMG signals for upper limb prosthesis control.

Pattern recognition methods for classifying user motion intent based on surface electromyography developed by research groups in well-controlled laboratory conditions are not yet clinically viable for upper limb prosthesis control, due to their limited robustness in users' real-life situations. To address this problem, a novel postprocessing algorithm, aiming to detect and remove misclassifications of a pattern recognition system of forearm and hand motions, is proposed. Using the maximum likelihood calculated by a classifier and the mean global muscle activity of the forearm, an artificial neural network was trained to detect potentially erroneous classification decisions. This system was compared to four previously proposed classification postprocessing methods, in both able-bodied and amputee subjects. Various nonstationarities were included in the experimental protocol to account for challenges posed in real-life settings, such as different contraction levels, static and dynamic motion phases, and effects induced by day-to-day transfers, such as electrode shifts, impedance changes, and psychometric user variability. The improvement in classification accuracy with respect to the unprocessed classifier ranged from 4.8% to 31.6%, depending on the scenarios investigated. The system significantly reduced misclassifications to wrong active classes and is thus a promising approach for improving the robustness of hand prosthesis controllability.

Extending mode switching to multiple degrees of freedom in hand prosthesis control is not efficient.

In recent years, many sophisticated control strategies for multifunctional dexterous hand prostheses have been developed. It was indeed assumed that control mechanisms based on switching between degrees of freedom, which are in use since the 1960's, could not be extended to efficient control of more than two degrees of freedom. However, quantitative proof for this assumption has not been shown. In this study, we adopted the mode switching paradigm available in commercial prostheses for two degree of freedom control and we extended it for the control of seven functions (3.5 degrees of freedom) in a modern robotic hand. We compared the controllability of this scaled version of the standard method to a state of the art pattern recognition based control in an applied online study. The aim was to quantify whether multi-functional prosthetic control with mode switching outperformed pattern recognition in the control of a real prosthetic hand for daily life activities online. Although in simple grasp-release tasks the conventional method performed best, tasks requiring more complex control of multiple degrees of freedom required a more intuitive control method, such as pattern recognition, for achieving high performance.

IgE peptide-specific CTL inhibit IgE production: a transient IgE suppression model in wild-type and HLA-A2.1 transgenic mice.

Effect of IgE peptide-specific CTL on IgE antibody production was studied in mouse models. CTL elicited in B6.A2Kb tg mice against a human IgE peptide nonamer, pWV, lysed human IgE-secreting U266 myeloma cells and inhibit IgE production by these cells. U266 transfected with mouse A2Kb transgene (U266-A2Kb) were optimally lysed by these CTL, because the alpha3 domain of A2Kb interacts well with the CD8 co-receptors. The CTL generated were more effective in inhibiting IgE production by U266-A2Kb cells than lysing these cells. IgE production by and progression of U266 myeloma were suppressed in B6.A2Kb tg mice rendered tolerant to these cells and vaccinated with pWV along with CpG. We also studied the CTL response elicited in wild-type mice by a mouse nonameric IgE peptide, PI-1, along with CpG. This treatment caused a transient suppression of the IgE response in mice previously sensitized to an antigen. In mice treated with this regimen repeatedly, the IgE response was fully recovered 20 days after each treatment. Notably, while IgE peptide/CpG-treated mice remained unresponsive to antigen challenge in vivo, antigen-specific IgE production can be elicited by antigen in cultured splenocytes from these mice. Moreover, IgE peptide/CpG also inhibited an on-going IgE response, including IgE production by bone marrow cells. Taken together, these observations indicate that a CTL-based IgE peptide vaccine targeting IgE-secreting B/plasma cells may be safely employed as a therapeutic approach for suppressing IgE production.

Many levels of control of V gene rearrangement frequency.

V, D, and J gene segments rearrange at very different frequencies. As with most biological systems, there are multiple levels of control of V gene recombination frequency, and here we review some of the work from our laboratory that addresses these various control mechanisms. One of the important factors that affect non-random V gene rearrangement frequency is the natural heterogeneity in recombination signal sequences (RSSs). Not only does variation in the heptamer and nonamer affect rearrangement, but variation in the spacer can also dramatically affect recombination. However, there are clearly other factors which control V gene rearrangement, as revealed by the fact that genes with identical RSSs can rearrange at different frequencies in vivo. Some of these other influences most likely affect the earliest stages of control--the change from an inaccessible state to an accessible state. Transcription factors can play a role in inducing these changes. Rearrangement of many VkappaI genes can be induced in a non-lymphoid cell line after ectopic expression of E2A, while neighboring VkappaII and VkappaIII genes do not rearrange, demonstrating that at least one level of control of induction of accessibility occurs at the level of the individual gene. Also, changes in chromatin structure can affect accessibility and might influence individual V gene rearrangement frequency.

Jejunal atresia related to the use of toluidine blue in genetic amniocentesis in twins.

Since 1990 avoidance of methylene blue as a dye in diagnostic amniocentesis is recommended. This is the result of the observation that a high incidence of jejuno-ileal atresia appeared in twin pregnancies following intraamniotic injection of methylene blue. We report a case of jejunal atresia in twins after injection of toluidine blue. We describe the clinical course, discuss possible teratogenic mechanisms and emphasize that no synthetic dyes should be used in second trimester amniocentesis.

High frequency of matrix attachment regions and cut-like protein x/CCAAT-displacement protein and B cell regulator of IgH transcription binding sites flanking Ig V region genes.

A major component in controlling V(D)J recombination is differential accessibility through localized changes in chromatin structure. Attachment of DNA to the nuclear matrix via matrix attachment region (MAR) sequences, and interaction with MAR-binding proteins have been shown to alter chromatin conformation, promote histone acetylation, and influence gene transcription. In this study, the flanking regions of several human and mouse Ig V(H) and Ig Vkappa genes were analyzed extensively for the presence of MARs by in vitro matrix-binding assay, and for interaction with the MAR-binding proteins cut-like protein x/CCAAT-displacement protein (Cux/CDP), B cell regulator of IgH transcription (Bright), and special AT-rich sequence-binding protein (SATB1) by EMSA. Cux/CDP and SATB1 are associated with repression, while Bright is an activator of Ig transcription. Binding sites were identified in the vicinity of all analyzed Ig V genes, and were also found flanking TCR Vbeta genes. We also show that the binding sites of the different factors do not always occur at MAR sequences. MAR sequences were also found within the Ig V loci at a much higher frequency than throughout the rest of the genome. Overall, the frequency and location of binding sites relative to the coding regions, and the strength of DNA-protein interaction showed much heterogeneity. Thus, variations in factor binding and MAR activity could potentially influence the extent of localized accessibility to V(D)J recombination and thus could play a role in unequal rearrangement of individual V genes. These sites could also contribute to effective transcription of Ig genes in mature and/or activated B cells, bringing both the promoter as well as the enhancer regions into close proximity at the nuclear matrix.