One of the hottest topics in rehabilitation robotics is that of proper control of prosthetic devices. Despite decades of research, the state of the art is dramatically behind the expectations. To shed light on this issue, in June, 2013 the first international workshop on Present and future of non-invasive peripheral nervous system (PNS)–Machine Interfaces (MI; PMI) was convened, hosted by the International Conference on Rehabilitation Robotics. The keyword PMI has been selected to denote human–machine interfaces targeted at the limb-deficient, mainly upper-limb amputees, dealing with signals gathered from the PNS in a non-invasive way, that is, from the surface of the residuum. The workshop was intended to provide an overview of the state of the art and future perspectives of such interfaces; this paper represents is a collection of opinions expressed by each and every researcher/group involved in it.

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BackgroundDexterous hand function is crucial for completing activities of daily living (ADLs), which typically require precise hand-object interactions. Kinematic analyses of hand trajectory, hand velocity, and grip aperture provide valuable mechanistic insights into task performance, but there is a need for standardized tasks representative of ADLs that are amenable to motion capture and show consistent performance in non-disabled individuals. Our objective was to develop two standardized functional upper limb tasks and to quantitatively characterize the kinematics of normative hand movement.MethodsTwenty non-disabled participants were recruited to perform two tasks: the Pasta Box Task and Cup Transfer Task. A 12-camera motion capture system was used to collect kinematic data from which hand movement and grip aperture measures were calculated. Measures reported for reach-grasp and transport-release segments were hand distance travelled, hand trajectory variability, movement time, peak and percent-to-peak hand velocity, number of movement units, peak and percent-to-peak grip aperture, and percent-to-peak hand deceleration. A between-session repeatability analysis was conducted on 10 participants.ResultsMovement times were longer for transport-release compared to reach-grasp for every movement. Hand and grip aperture measures had low variability, with 55 out of 63 measures showing good repeatability (ICC > 0.75). Cross-body movements in the Pasta Box Task had longer movement times and reduced percent-to-peak hand velocity values. The Cup Transfer Task showed decoupling of peak grip aperture and peak hand deceleration for all movements. Movements requiring the clearing of an obstacle while transporting an object displayed a double velocity peak and typically a longer deceleration phase.DiscussionNormative hand kinematics for two standardized functional tasks challenging various aspects of hand-object interactions important for ADLs showed excellent repeatability. The consistency in normative task performance across a variety of task demands shows promise as a potential outcome assessment for populations with upper limb impairment.

Purpose Despite new treatments, acute myeloid leukemia (AML) remains an incurable disease. More effective drug design requires an expanded view of the molecular complexity that underlies AML. Alternative splicing of RNA is used by normal cells to generate protein diversity. Growing evidence indicates that aberrant splicing of genes plays a key role in cancer. We investigated genome-wide splicing abnormalities in AML and based on these abnormalities, we aimed to identify novel potential biomarkers and therapeutic targets. Experimental Design We used genome-wide alternative splicing screening to investigate alternative splicing abnormalities in two independent AML patient cohorts [Dana-Farber Cancer Institute (DFCI) (Boston, MA) and University Hospital de Nantes (UHN) (Nantes, France)] and normal donors. Selected splicing events were confirmed through cloning and sequencing analysis, and than validated in 193 patients with AML. Results Our results show that approximately 29% of expressed genes genome-wide were differentially and recurrently spliced in patients with AML compared with normal donors bone marrow CD34+ cells. Results were reproducible in two independent AML cohorts. In both cohorts, annotation analyses indicated similar proportions of differentially spliced genes encoding several oncogenes, tumor suppressor proteins, splicing factors, and heterogeneous-nuclear-ribonucleoproteins, proteins involved in apoptosis, cell proliferation, and spliceosome assembly. Our findings are consistent with reports for other malignances and indicate that AML-specific aberrations in splicing mechanisms are a hallmark of AML pathogenesis. Conclusions Overall, our results suggest that aberrant splicing is a common characteristic for AML. Our findings also suggest that splice variant transcripts that are the result of splicing aberrations create novel disease markers and provide potential targets for small molecules or antibody therapeutics for this disease.