188 research outputs found

    Current Performance and On-Going Improvements of the 8.2 m Subaru Telescope

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    An overview of the current status of the 8.2 m Subaru Telescope constructed and operated at Mauna Kea, Hawaii, by the National Astronomical Observatory of Japan is presented. The basic design concept and the verified performance of the telescope system are described. Also given are the status of the instrument package offered to the astronomical community, the status of operation, and some of the future plans. The status of the telescope reported in a number of SPIE papers as of the summer of 2002 are incorporated with some updates included as of 2004 February. However, readers are encouraged to check the most updated status of the telescope through the home page, http://subarutelescope.org/index.html, and/or the direct contact with the observatory staff.Comment: 18 pages (17 pages in published version), 29 figures (GIF format), This is the version before the galley proo

    Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

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    Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (, , ) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types

    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

    stairs and fire

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    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 importância 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

    Device-associated nosocomial infections in 55 intensive care units of 8 developing countries

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    Q1Q1582-91Background: Health care-associated infections from invasive medical devices in the intensive care unit (ICU) are a major threat to patient safety. Most published studies of ICU-acquired infections have come from industrialized western countries. In a Centers for Disease Control and Prevention (CDC) National Nosocomial Infections Surveillance (NNIS) System report, the U.S. pooled mean rates of central venous catheter (CVC)-related bloodstream infections, ventilator-associated pneumonia, and catheter-associated urinary tract infections were 4.0 per 1000 CVC days, 5.4 per 1000 mechanical ventilator days, and 3.9 per Foley catheter days, respectively. Objective: To ascertain the incidence of device-associated infections in the ICUs of developing countries. Design: Multicenter, prospective cohort surveillance of device-associated infection by using the CDC NNIS System definitions. Setting: 55 ICUs of 46 hospitals in Argentina, Brazil, Colombia, India, Mexico, Morocco, Peru, and Turkey that are members of the International Nosocomial Infection Control Consortium (INICC). Measurements: Rates of device-associated infection per 100 patients and per 1000 device days. Results: During 2002-2005, 21,069 patients who were hospitalized in ICUs for an aggregate 137,740 days acquired 3095 device-associated infections for an overall rate of 14.7% or 22.5 infections per 1000 ICU days. Ventilator-associated pneumonia posed the greatest risk (41% of all device-associated infections or 24.1 cases [range, 10.0 to 52.7 cases] per 1000 ventilator days), followed by CVC-related bloodstream infections (30% of all device-associated infections or 12.5 cases [range, 7.8 to 18.5 cases] per 1000 catheter days) and catheter-associated urinary tract infections (29% of all device-associated infections or 8.9 cases [range, 1.7 to 12.8 cases] per 1000 catheter days). Notably, 84% of Staphylococcus aureus infections were caused by methicillin-resistant strains, 51% of Enterobacteriaceae isolates were resistant to ceftriaxone, and 59% of Pseudomonas aeruginosa isolates were resistant to fluoroquinolones. The crude mortality rate for patients with device-associated infections ranged from 35.2% (for CVC-associated bloodstream infection) to 44.9% (for ventilator-associated pneumonia). Limitations: These initial data are not adequate to represent any entire country, and likely variations in the efficiency of surveillance and institutional resources may have affected the rates that were detected. Conclusions: Device-associated infections in the ICUs of these developing countries pose greater threats to patient safety than in U.S. ICUs. Active infection control programs that perform surveillance of infection and implement guidelines for prevention can improve patient safety and must become a priority in every country

    Impact of International Nosocomial Infection Control Consortium (INICC) strategy on central line-associated bloodstream infection rates in the intensive careunits of 15 developing countries

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    Q2Q11264-1272Background The International Nosocomial Infection Control Consortium (INICC) was established in 15 developing countries to reduce infection rates in resource-limited hospitals by focusing on education and feedback of outcome surveillance (infection rates) and process surveillance (adherence to infection control measures). We report a time-sequence analysis of the effectiveness of this approach in reducing rates of central line–associated bloodstream infection (CLABSI) and associated deaths in 86 intensive care units with a minimum of 6-month INICC membership. Methods Pooled CLABSI rates during the first 3 months (baseline) were compared with rates at 6-month intervals during the first 24 months in 53,719 patients (190,905 central line–days). Process surveillance results at baseline were compared with intervention period data. Results During the first 6 months, CLABSI incidence decreased by 33% (from 14.5 to 9.7 CLABSIs per 1,000 central line–days). Over the first 24 months there was a cumulative reduction from baseline of 54% (from 16.0 to 7.4 CLABSIs per 1,000 central line–days; relative risk, 0.46 [95% confidence interval, 0.33–0.63]; P <.001). The number of deaths in patients with CLABSI decreased by 58%. During the intervention period, hand hygiene adherence improved from 50% to 60% (P<.001); the percentage of intensive care units that used maximal sterile barriers at insertion increased from 45% to 85% (P < .001), that adopted Chlorhexidine for antisepsis increased from 7% to 27% (P = .018), and that sought to remove unneeded catheters increased from 37% to 83% (P = .004); and the duration of central line placement decreased from 4.1 to 3.5 days (P < .001). Conclusions Education, performance feedback, and outcome and process surveillance of CLABSI rates significantly improved infection control adherence, reducing the CLABSI incidence by 54% and the number of CLABSI-associated deaths by 58% in INICC hospitals during the first 2 years
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