Preventing adolescents’ externalizing and internalizing symptoms : effects of the Penn Resiliency Program

This study reports secondary outcome analyses from a past study of the Penn Resiliency Program (PRP), a cognitive-behavioral depression prevention program for middle-school aged children. Middle school students (N = 697) were randomly assigned to PRP, PEP (an alternate intervention), or control conditions. Gillham et al., (2007) reported analyses examining PRP’s effects on average and clinical levels of depression symptoms. We examine PRP’s effects on parent-, teacher-, and self-reports of adolescents’ externalizing and broader internalizing (depression/anxiety, somatic complaints, and social withdrawal) symptoms over three years of follow-up. Relative to no intervention control, PRP reduced parent-reports of adolescents’ internalizing symptoms beginning at the first assessment after the intervention and persisting for most of the follow-up assessments. PRP also reduced parent-reported conduct problems relative to no-intervention. There was no evidence that the PRP program produced an effect on teacher- or self-report of adolescents’ symptoms. Overall, PRP did not reduce symptoms relative to the alternate intervention, although there is a suggestion of a delayed effect for conduct problems. These findings are discussed with attention to developmental trajectories and the importance of interventions that address common risk factors for diverse forms of negative outcomes.peer-reviewe

Science Extraction from TESS Observations of Known Exoplanet Hosts

The transit method of exoplanet discovery and characterization has enabled numerous breakthroughs in exoplanetary science. These include measurements of planetary radii, mass-radius relationships, stellar obliquities, bulk density constraints on interior models, and transmission spectroscopy as a means to study planetary atmospheres. The Transiting Exoplanet Survey Satellite (TESS) has added to the exoplanet inventory by observing a significant fraction of the celestial sphere, including many stars already known to host exoplanets. Here we describe the science extraction from TESS observations of known exoplanet hosts during the primary mission. These include transit detection of known exoplanets, discovery of additional exoplanets, detection of phase signatures and secondary eclipses, transit ephemeris refinement, and asteroseismology as a means to improve stellar and planetary parameters. We provide the statistics of TESS known host observations during Cycle 1 & 2, and present several examples of TESS photometry for known host stars observed with a long baseline. We outline the major discoveries from observations of known hosts during the primary mission. Finally, we describe the case for further observations of known exoplanet hosts during the TESS extended mission and the expected science yield.Comment: 12 pages, 7 figures, accepted for publication in PAS

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

Neural activation to loss and reward among alcohol naive adolescents who later initiate alcohol use

Adolescent alcohol use is associated with adverse psychosocial outcomes, including an increased risk of alcohol use disorder in adulthood. It is therefore important to identify risk factors of alcohol initiation in adolescence. Research to date has shown that altered neural activation to reward is associated with alcohol use in adolescence; however, few studies have focused on neural activation to loss and alcohol use. The current study examined neural activation to loss and reward among 64 alcohol naive 12−14 year olds that did (n = 20) and did not initiate alcohol use by a three year follow-up period. Results showed that compared to adolescents that did not initiate alcohol use, adolescents that did initiate alcohol use by the three year follow-up period had increased activation to loss in the left striatum (i.e., putamen), right precuneus, and the brainstem/pons when they were alcohol naive at baseline. By contrast, alcohol initiation was not associated with neural activation to winning a reward. These results suggest that increased activation in brain regions implicated in salience, error detection/self-referential processing, and sensorimotor function, especially to negative outcomes, may represent an initial vulnerability factor for alcohol use in adolescence