Fine Motor Skills and Executive Function Both Contribute to Kindergarten Achievement

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92367/1/j.1467-8624.2012.01768.x.pd

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

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

Building a Critical Web Design Toolkit

How do issues like sustainability, accessibility, the global digital divide, and social justice come to play in choices about web development tools? The Critical Web Design Toolkit is a resource for developing static websites around minimal computing practices and helping students and researchers consider these issues. In this presentation, the project team will demonstrate our site template and talk about the process of building it. While static site web development offers benefits in environmental sustainability, low-bandwidth access, and accessibility for users with disabilities, there are skill barriers compared to using than popular database-driven content management systems like WordPress, Omeka, and Scalar. Our team aimed to address the \u27whys\u27 and \u27hows\u27 of static site development, to make it easier for Bryn Mawr community members to create static digital projects, and to empower those who are new to web publishing to explore static technologies. The Digital Scholarship Summer Fellows spent 10 weeks learning about web development, digital scholarship and the social and political impact of internet technologies. They designed our template to be a simple, accessible, user-oriented, and compelling, and built skills in html, css, jekyll, and liquid in order to realize that vision. They created robust documentation and learning resources that invite users to explore ideas of critical web design and learn how to publish resources with ethics and social justice in mind. Finally, they tested out our template and documentation with users in the community, and used their feedback to improve our project

PRE-LOADED BETAINE IMPROVES THERMOREGULATION WHEN CYCLING IN THE HEAT

BACKGROUND: Heat-related illness compromises health and performance in endurance athletes during training and competition. Betaine (BET) is a nutrient that has been previously identified in animal models to act as an osmolyte and attenuates the effects of thermal stress. However, much of the prior research has only assessed the efficacy of preloading BET in passive heat models. Therefore, the purpose of this study is to examine the effects of preloaded BET in an active heat model. METHODS: Eight endurance-trained males (age 26.4 ± 6.8 years; VO2 Peak 55.5 ± 4.8 mL/kg/min) completed 60 min of cycling at 70% VO2 peak in a hot environment (33° C, 35% RH) after a 7-day supplement loading protocol (50 mg/kg, 2x daily) of placebo (PLA) or BET in a double blind, randomized, counterbalanced, crossover study. Core temperature and thermal sensation were measured at rest and every 10 minutes throughout the active heat protocol. Nude body weight was measured prior to- and immediately post-exercise to calculate sweat rate. No fluid ingestion was allowed during this time. Blood samples were collected at rest, 30 minutes, and immediately after exercise. Visual analog scales were administered before and immediately after exercise to quantify sensations of thirst. Bioelectrical impedance assessed fluid compartments before and after the respective supplementation weeks. RESULTS: Area under curve analysis identified BET as having a smaller overall increase in core body temperature compared to PLA (p = 0.012). Further analysis showed ending core temperature was significantly lower in BET (-0.023 ° C; p = 0.029) than PLA. BET also resulted in a significant increase in sweat rate (mean difference = 0.19 ± 0.20 L/hr; p = 0.02). Blood assessments revealed BET had lower hematocrit at the mid-exercise timepoint compared to PLA (BET: 48.3%; PLA: 50.8%; p = 0.02). Increases in total body water (TBW) and intracellular fluid (ICF) in the BET condition approached significance compared to PLA (TBW: +1.69 L, p = 0.055; ICF: +1.39L, p = 0.066). No significant differences were found between conditions in subjective measures of thermal sensation or thirst (p = 0.318; p = 0.862). CONCLUSION: BET supplementation may have the capacity to mitigate the rise in core body temperature and maintain plasma volume during exercise in an uncompensable heat stress environment, despite having no significant effect on subjective sensations of heat stress