A Decision Support System to Provide an Ongoing Prediction of Robot-Assisted Rehabilitation Outcome in Stroke Survivors.

Clinicians often deal with complex robotic platform and serious games in stroke patients rehabilitation contexts, and they face two main problems: 1) the interpretation of either the performance in game or measures of a robotic system from the motor recovery point of view, and 2) the duration and complexity of clinical scales administration that makes repetitive assessments during the therapy unpractical. In this paper, a Random Tree Forest based system was trained and tested to provide a prediction of different clinical outcomes (i.e. FMA, ARAT, and MI) along the whole therapy duration, having non-clinical measures only as inputs, acting as a simulated decision support system. The dataset includes 30 post-stroke patients, that underwent a 30-session robot-assisted rehabilitation treatment. Results have shown that the system is able to produce very accurate and reliable predictions about the motor recovery of the patient at the end of the therapy, already in the first phases of the rehabilitation (i40% of therapy execution), just using robotic platform measures. Such a tool would provide a great benefit in terms of rehabilitation objectives planning, as a decision support tool for highly personalized rehabilitation treatments.

A Random Tree Forest decision support system to personalize upper extremity robot-assisted rehabilitation in stroke: a pilot study.

Robotic-based rehabilitation administered by means of serious games certainly represents the frontier of rehabilitation treatments, offering a high degree of customization of therapy, to meet individual patients' needs and to tailor a proper rehabilitation therapy. Despite the rush on developing complex rehabilitation systems, they often do not provide clinicians with long-term information about the outcome of rehabilitation, thus, not supporting them in the initial set-up phase of the therapy. In this paper, a Random-Forest based system was trained and tested to provide a prediction at discharge of several clinical scales outcomes (i.e. FMA, ARAT, and MI), having clinical scale scores and measures from the robotic system at the enrollment as inputs. The dataset includes 25 post-stroke patients from different clinics, that underwent a variable number of days of rehabilitation with a robotic treatment. Results have shown that the system is able to predict the final outcome with an accuracy ranging from 60% to 73% on the selected scales. Also results provide information on which variables are more relevant for the prediction of outcome of therapy, in particular clinical scales scores such as FMA, ARAT, MI, NRS, PCS, and MCS and robotic automatically extracted measurements related to patient's work expenditure and time. This supports the idea of using such a system in a clinical environment in a decision support tool for clinicians.

Parallel conduction of the phase I preventive and therapeutic trials based on the Tat vaccine candidate.

The native HIV-1 Tat protein was chosen as vaccine candidate for phase I clinical trials in both uninfected (ClinicalTrials.gov identifier: NCT00529698) and infected volunteers (ClinicalTrials.gov identifier: NCT00505401). The rationale was based on the role of Tat in the natural infection and AIDS pathogenesis, on the association of Tat-specific immune responses with the asymptomatic stage and slow-progression rate as well as on its sequence conservation among HIV clades (http://www.hiv1tat-vaccines.info/). The parallel conduction in the same clinical centers of randomized, double blind, placebo-controlled phase I studies both in healthy, immunologically competent adults and in HIV-infected, clinically asymptomatic, individuals represents a unique occasion to compare the vaccine-induced immune response in both the preventive and therapeutic setting. In both studies, the same lot of the native Tat protein was administered 5 times, every four weeks, subcute (SC) with alum adjuvant or intradermic (ID), in the absence of adjuvant, at 7.5 microg, 15 microg or 30 microg doses, respectively. The primary and secondary endpoints of these studies were the safety and immunogenicity of the vaccine candidate, respectively. The study lasted 52 weeks and monitoring was conducted for on additional 3 years. The results of both studies indicated that the Tat vaccine is safe and well tolerated both locally and systemically and it is highly immunogenic at all the dosages and by both routes of administration. Vaccination with Tat induced a balanced immune response in uninfected and infected individuals. In particular, therapeutic immunization induced functional antibodies and partially reverted the marked Th1 polarization of anti-Tat immunity seen in natural infection, and elicited a more balanced Th1/Th2 immune response. Further, the number of CD4 T cells correlated positively with anti-Tat antibody titers. Based on these results, a phase II study is ongoing in infected drug-treated individuals (http://www.hiv1tat-vaccines.info/).

Red blood cell-mediated delivery of recombinant HIV-1 Tat protein in mice induces anti-Tat neutralizing antibodies and CTL.

The immunotherapeutic potential of biologically active HIV-1 Tat protein coupled to autologous red blood cells (RBCs) was evaluated in a mouse model. HIV-1 Tat expressed in Escherichia coli and purified to homogeneity was found to be active in viral trans activation and efficiently internalised by monocyte-derived dendritic cells (MDDCs). The product of HIV-Tat biotinylation and coupling to RBCs by means of a biotin-avidin-biotin bridge, (RBC-Tat), showed no trans activation activity and was still efficiently internalized by MDDCs as compared to uncoupled Tat.Balb/c mice were then immunized with 10 microg of soluble Tat in complete Freund's adjuvant or with 40 ng of Tat coupled on RBCs surface and boosted at week 3, 6 and 25 with 5 microg soluble Tat in incomplete Freund's adjuvant or with 20 ng of RBC-coupled Tat, respectively. Anti-Tat antibody response was similar in both groups; however, 2/6 animals immunized with soluble Tat and 6/6 animals immunized with RBC-Tat developed anti-Tat neutralizing antibodies. In addition, at week 28 cytolytic anti-Tat CTLs were detected in all animals although they were slightly higher in mice immunized with RBC-Tat. These results indicate that RBC-mediated delivery of HIV-1 Tat, in amounts 250 times lower than soluble Tat, is safe and induces specific CTL responses and neutralizing antibodies.