79 research outputs found

    Lights, Camera, Empathy: A Request to Slow the Emergency Medicine Standardized Video Interview Project Study

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141594/1/aet210062_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141594/2/aet210062.pd

    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

    Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

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    A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importñncia de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació

    stairs and fire

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    ESCAPE AS REINFORCEMENT AND ESCAPE EXTINCTION IN THE TREATMENT OF FEEDING PROBLEMS

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    Given the effectiveness of putative escape extinction as treatment for feeding problems, it is surprising that little is known about the effects of escape as reinforcement for appropriate eating during treatment. In the current investigation, we examined the effectiveness of escape as reinforcement for mouth clean (a product measure of swallowing), escape as reinforcement for mouth clean plus escape extinction (EE), and EE alone as treatment for the food refusal of 5 children. Results were similar to those of previous studies, in that reinforcement alone did not result in increases in mouth clean or decreases in inappropriate behavior (e.g., Piazza, Patel, Gulotta, Sevin, & Layer, 2003). Increases in mouth clean and decreases in inappropriate behavior occurred when the therapist implemented EE independent of the presence or absence of reinforcement. Results are discussed in terms of the role of negative reinforcement in the etiology and treatment of feeding problems

    TESS Spots a Super-puff: The Remarkably Low Density of TOI-1420b

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    We present the discovery of TOI-1420b, an exceptionally low-density ( ρ = 0.08 ± 0.02 g cm ^−3 ) transiting planet in a P = 6.96 days orbit around a late G-dwarf star. Using transit observations from TESS, LCOGT, Observatoire PrivĂ© du Mont, Whitin, Wendelstein, OAUV, Ca l’Ou, and KeplerCam, along with radial velocity observations from HARPS-N and NEID, we find that the planet has a radius of R _p = 11.9 ± 0.3 R _⊕ and a mass of M _p = 25.1 ± 3.8 M _⊕ . TOI-1420b is the largest known planet with a mass less than 50 M _⊕ , indicating that it contains a sizeable envelope of hydrogen and helium. We determine TOI-1420b’s envelope mass fraction to be fenv=82−6+7%{f}_{\mathrm{env}}={82}_{-6}^{+7} \% , suggesting that runaway gas accretion occurred when its core was at most four to five times the mass of the Earth. TOI-1420b is similar to the planet WASP-107b in mass, radius, density, and orbital period, so a comparison of these two systems may help reveal the origins of close-in low-density planets. With an atmospheric scale height of 1950 km, a transmission spectroscopy metric of 580, and a predicted Rossiter–McLaughlin amplitude of about 17 m s ^−1 , TOI-1420b is an excellent target for future atmospheric and dynamical characterization

    TESS Spots a Super-puff: The Remarkably Low Density of TOI-1420b

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    We present the discovery of TOI-1420b, an exceptionally low-density (ρ = 0.08 ± 0.02 g cm−3) transiting planet in a P = 6.96 days orbit around a late G-dwarf star. Using transit observations from TESS, LCOGT, Observatoire PrivĂ© du Mont, Whitin, Wendelstein, OAUV, Ca l'Ou, and KeplerCam, along with radial velocity observations from HARPS-N and NEID, we find that the planet has a radius of Rp = 11.9 ± 0.3R⊕ and a mass of Mp = 25.1 ± 3.8M⊕. TOI-1420b is the largest known planet with a mass less than 50M⊕, indicating that it contains a sizeable envelope of hydrogen and helium.<br/
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