6 research outputs found

    Unicorns: Past, Present and in the Imagination

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    In the last few thousand years, unicorn folklore has extensively evolved. In fact, the evolution of the mentioned above mythical creature has been so drastic, that the original unicorn lore of the Greek, Roman and early Christian people, would be unrecognizable to a modern day person. Consequently, to the historical figures (such as Julius Caesar and Ctesias) that contributed to the creation of the mythical creature, they would not recognize the unicorn as it is found in My Little Pony or any other pop culture sensation. To discover the cause of disconnect between the folkloric and pop culture unicorns, an in depth look at the unicorn’s journey from historic to modern times, will be evaluated. Specifically the original creation of the creature, Christian influence, the cultural diffusion that has led to hybrid creatures such as the pegacorn, unipeg, and alicorns,will all be examined. Then finally, the changes that the unicorn has underwent, will be used to lead up to an explanation on how these folkloric animals became the gentle /horrifying unicorns of modern children’s entertainment

    Do pediatric hospitalizations have a unique geography?

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    BACKGROUND: In the U.S. small-area health services research studies are often based on the hospital service areas (HSAs) defined by the Dartmouth Atlas of Healthcare project. These areas are based on the geographic origins of Medicare Part A hospital patients, the great majority of whom are seniors. It is reasonable to question whether the geographic system so defined is appropriate for health services research for all ages, particularly for children, who have a very different system of healthcare financing and provision in the U.S. METHODS: This article assesses the need for a unique system of HSAs to support pediatric small-area analyses. It is a cross-sectional analysis of California hospital discharges for two age groups – non-newborns 0–17 years old, and seniors. The measure of interest was index of localization, which is the percentage of HSA residents hospitalized in their home HSA. Indices were computed separately for each age group, and index agreement was assessed for 219 of the state's HSAs. We examined the effect of local pediatric inpatient volume and pediatric inpatient resources on the divergence of the age group indices. We also created a new system of HSAs based solely on pediatric patient origins, and visually compared maps of the traditional and the new system. RESULTS: The mean localization index for pediatric discharges was 20 percentage points lower than for Medicare cases, indicating a poorer fit of the traditional geographic system for children. The volume of pediatric cases did not appear to be associated with the magnitude of index divergence between the two age groups. Pediatric medical and surgical case subgroups gave very similar results, and both groups differed substantially from seniors. Location of children's hospitals and local pediatric bed supply were associated with Medicare-pediatric divergence. There was little visual correspondence between the maps of traditional and pediatric-specific HSAs. CONCLUSION: Children and seniors have significantly different geographic patterns of hospitalization in California. Medicare-based HSAs may not be appropriate for all age groups and service types throughout the U.S

    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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