64 research outputs found

    Behavioral Contract

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    The purpose of this poster is to answer the questions: a) How can behavior contracts be utilized in the classroom; and b) How effective are behavioral contracts in a classroom behavior management system? The related research includes an article that demonstrated the effectiveness of using behavioral contracts with middle school students who were labeled with Emotional and Behavioral Disorders (EBD). When behavior contracts were in place the inappropriate behavior within the classroom decreased. Behavior contracts seem to be effective for behavior modification of middle school students. It is recommended that behavior contracts be considered for use in classrooms or individual behavior modification plans

    Rabbit Knee Joint Biomechanics: Motion Analysis and Modeling of Forces during Hopping

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    Although the rabbit hindlimb has been commonly used as an experimental animal model for studies of osteoarthritis, bone growth and fracture healing, the in vivo biomechanics of the rabbit knee joint have not been quantified. The purpose of this study was to investigate the kinematic and kinetic patterns during hopping of the adult rabbit, and to develop a model to estimate the joint contact force distribution between the tibial plateaus. Force platform data and three-dimensional motion analysis using infrared markers mounted on intracortical bone pins were combined to calculate the knee and ankle joint intersegmental forces and moments. A statically determinate model was developed to predict muscle, ligament and tibiofemoral joint contact forces during the stance phase of hopping. Variations in hindlimb kinematics permitted the identification of two landing patterns, that could be distinguished by variations in the magnitude of the external knee abduction moment. During hopping, the prevalence of an external abduction moment led to the prediction of higher joint contact forces passing through the lateral compartment as compared to the medial compartment of the knee joint. These results represent critical data on the in vivo biomechanics of the rabbit knee joint, which allow for comparisons to both other experimental animal models and the human knee, and may provide further insight into the relationships between mechanical loading, osteoarthritis, bone growth, and fracture healing

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
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