Interpreting response time effects in functional imaging studies

It has been suggested that differential neural activity in imaging studies is most informative if it is independent of response time (RT) differences. However, others view RT as a behavioural index of key cognitive processes, which is likely linked to underlying neural activity. Here, we reconcile these views using the effort and engagement framework developed by Taylor, Rastle, and Davis (2013) and data from the domain of reading aloud. We propose that differences in neural engagement should be independent of RT, whereas, differences in neural effort should co-vary with RT. We illustrate these different mechanisms using data from an fMRI study of neural activity during reading aloud of regular words, irregular words, and pseudowords. In line with our proposals, activation revealed by contrasts designed to tap differences in neural engagement (e.g., words are meaningful and therefore engage semantic representations more than pseudowords) survived correction for RT, whereas activation for contrasts designed to tap differences in neural effort (e.g., it is more difficult to generate the pronunciation of pseudowords than words) correlated with RT. However, even for contrasts designed to tap neural effort, activity remained after factoring out the RT-BOLD response correlation. This may reveal unpredicted differences in neural engagement (e.g., learning phonological forms for pseudowords. >. words) that could further the development of cognitive models of reading aloud. Our framework provides a theoretically well-grounded and easily implemented method for analysing and interpreting RT effects in neuroimaging studies of cognitive processes

Functional redundancy between RAP1 isoforms in murine platelet production and function

RAP GTPases, important regulators of cellular adhesion, are abundant signaling molecules in the platelet/megakaryocytic lineage. However, mice lacking the predominant isoform, RAP1B, display a partial platelet integrin activation defect and have a normal platelet count, suggesting the existence of a RAP1-independent pathway to integrin activation in platelets and a negligible role for RAP GTPases in megakaryocyte biology. To determine the importance of individual RAP isoforms on platelet production and on platelet activation at sites of mechanical injury or vascular leakage, we conditionally deleted Rap1a and/or Rap1b in the megakaryocytic lineage (mKO). Interestingly, Rap1a/b-mKO mice displayed a marked macrothrombocytopenia due to impaired pro- platelet formation by megakaryocytes. In platelets, RAP isoforms had both redundant and isoform-ˇspecific functions. Deletion of RAP1B, but not RAP1A, significantly reduced α- granule secretion and activation of the cytoskeleton regulator RAC1. Both isoforms significantly contributed to thromboxane A2 generation and the inside-out activation of platelet integrins. Combined deficiency of RAP1A and RAP1B markedly impaired platelet aggregation, spreading and clot retraction. Consistently, thrombus formation in physiological flow conditions was abolished in Rap1a/b-mKO, but not Rap1a-mKO or Rap1b-mKO platelets. Rap1a/b-mKO mice were strongly protected from experimental thrombosis and exhibited a severe defect in hemostasis after mechanical injury. Surprisingly, Rap1a/b-mKO platelets were indistinguishable from controls in their ability to prevent blood-lymphatic mixing during development and hemorrhage at sites of inflammation. In summary, our studies demonstrate an essential role for RAP1 signaling in platelet integrin activation and a critical role in platelet production. While important for hemostatic/thrombotic plug formation, platelet RAP1 signaling is dispensable for vascular integrity during development and inflammation

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

AN ANALYSIS OF CODING BEHAVIOR

Abstract not availabl

Social Origins of Psychological Well-Being among older Korean Immigrants

The present study investigates the social sources of psychological well-being of older Korean immigrants in terms of social contexts and acculturation level. Data were collected from a survey of older Koreans in Chicago. This study confirms empirically the target population as a vulnerable group. Effects of social sources were examined with multiple regression analysis. -and the main results are: (I) larger primary networks and independent altitudes on children's support are functional for older Korean immigrants' psychological well-being; (2) life stress is more useful for explaining current depressive symptoms; (3) residing in the ethnic community is functional for their life satisfaction; (4) age is an important predictor for the efficacy of adjustment of older persons; and (5) health status is an overall predictor of psychological well-being

African-American adolescent girls' initiation of sexual activity: survival analysis

Purpose: African American adolescent females tend to initiate participation in sexual activity at an earlier age than Caucasian adolescent females. Early initial participation in sexual activity is associated with increased HIV risk. However, limited prospective data are available on the rate at which African American adolescent females delay their initial participation in sexual activity. The purpose is to determine low-income inner city African American adolescent females’ survival or continued non-participation in sexual activity over a 20-month period and to determine predictors associated with survival. Methods: A longitudinal quasi-experimental research design with multiple data collection points was used. The convenience sample consisted of 396 African American females with a mean age of 12.4 years (SD = 1.1 years) and their mothers. The adolescents completed questionnaires assessing perceptions of maternal monitoring, HIV transmission knowledge, self-efficacy to refuse sex, intention to refuse sex, and age. Their mothers completed questionnaires assessing perception of maternal monitoring, safer sex self-efficacy, marital status, and educational level. At baseline, the adolescents reported non-participation in sexual activity. Survival analysis was conducted to determine the timing and predictors of sexual activity initiation for these adolescents. Findings: Of the 396 adolescents, 28.5% did not survive; they participated in sexual activity within the 20-month period. Predictors of non-survival were the adolescents’ age, perception of maternal monitoring, and intention to refuse sex. Conclusion: Findings suggest interventions that increase maternal monitoring and adolescents’ intentions to refuse sex could be beneficial in delaying sexual activity

Peer Group Intervention for HIV Prevention among Health Workers in Chile

We tested the impacts of a professionally assisted peer group intervention on Chilean health workers' HIV-related knowledge, attitudes, and behaviors using a quasi-experimental design with a pretest and 3-month posttest. Two Santiago suburbs were randomly assigned to the intervention or delayed intervention control condition, and five community clinics per suburb participated. Interested workers at the intervention ( n = 262) and control ( n = 293) clinics participated and completed both evaluations. At posttest, intervention clinic workers had higher knowledge and more positive attitudes regarding HIV, condoms, stigmatization, and self-efficacy for prevention. They reported more partner discussion about safer sex, less unprotected sex, and more involvement in HIV prevention activities in the clinic and the community, but they did not report fewer sexual partners or more standard precautions behaviors. Because of these positive impacts, the program will become a regular continuing education unit that can be used to meet health worker licensing requirements

Genesis of Marine Terrace Soils, Barbados, West Indies: Evidence from Mineralogy and Geochemistry

Well-developed, clay-rich soils dominated by interstratified kaolinite-smectite are found on the uplifted coral reef terraces on the island of Barbados. The reef limestone is unlikely to have been the soil parent material however, because it is 98 per cent CaCO, and geomorphic evidence argues against the 20 m of reef solution required to produce the soils by this process. The mineralogy of the sand, silt, and clay fractions of the soils, and trace element geochemistry, suggest that aeolian materials carried on the trade winds from Africa, volcanic ash from the island of St. Vincent, and quartz from Tertiary bedrock on the island itself are the parent materials for the soils

Geochemical Evidence of Saharan Dust Parent Material for Soils Developed on Quaternary Limestones of Caribbean and Western Atlantic Islands

Most previous workers have regarded the insoluble residues of high-purity Quatemary limestones (coral reefs and oolites) as the most important parent material for well-developed, clay-rich soils on Caribbean and western Atlantic islands, but this genetic mechanism requires unreasonable amounts of limestone solution in Quatemary time. Other possible parent materials from external sources are volcanic ash from the Lesser Antilles island arc and Saharan dust carried across the Atlantic Ocean on the northeast trade winds. Soils on Quatemary coral terraces and carbonate eolianites on Barbados, Jamaica, the Florida Keys (United States), and New Providence Island (Bahamas) were studied to determine which, if either, external source was important. Caribbean volcanic ashes and Saharan dust can be clearly distinguished using ratios of relatively immobile elements (Al,O,/‘I’iO,, Ti, Ti/Zr, and TifI’h). Comparison of these ratios in 25 soils, where estimated ages range from 125,000 to about 870,000 yr, shows that Saharan dust is the most important parent material for soils on all islands. These results indicate that the northeast trade winds have been an important component of the regional climatology for much of the Quaterary. Saharan dust may also be an important parent material for Caribbean island bauxites of much greater age

Effects of health literacy on health status and health service utilization amongst the elderly

Amid increased concerns about the adverse consequences of low health literacy, it remains unclear how health literacy affects health status and health service utilization. With a sample of 489 elderly Medicare patients in a Midwestern city in the USA, we explored the intermediate factors that may link health literacy to health status and utilization of health services such as hospitalization and emergency care. We expected to find that individuals with higher health literacy would have better health status and less frequent use of emergency room and hospital services due to (1) greater disease knowledge, (2) healthier behaviors, (3) greater use of preventive care, and (4) a higher degree of compliance with medication. Using path analysis, we found, however, that health literacy had direct effects on health outcomes and that none of these variables of interest was a significant intermediate factor through which health literacy affected use of hospital services. Our findings suggest that improving health literacy may be an effective strategy to improve health status and to reduce the use of expensive hospital and emergency room services among elderly patients.Health literacy Health Health service utilization Health status USA Elderly