Codevelopment of delinquent and depressive symptoms across adolescence: time-invariant and time-varying effects of school and social failure.

The codevelopment of delinquent behaviors and depressive symptoms from Grade 9 to 11 was investigated on an Italian sample of 518 adolescents (399 male) after the transition to high school, evaluating the time-invariant effects of past school failure and social failure and the time-varying effects of school achievement and social problems. Bivariate latent growth model showed a positive correlation between the two intercepts and the two slopes, suggesting that during adolescence the two trajectories are reciprocally and causally related over time. Time-invariant predictors--past school failure and social failure--explain interindividual variability only for delinquent growth. Time-varying covariates--school achievement and social problems--are significantly associated with both trajectories. These time-varying variables can act as snares, mechanisms responsible for accelerating the otherwise normative pattern of increase of delinquent behaviors and actively retarding the normative decrease of depressive symptoms over adolescence. Findings highlight how interventions aimed to promote competence during adolescence can be an effective way to prevent psychopathology or to reduce its impact.

Optimizing pemetrexed-gemcitabine combination in patients with advanced non-small cell lung cancer: a pharmacogenetic approach.

INTRODUCTION: The pemetrexed-gemcitabine combination is effective in patients with non-small cell lung cancer (NSCLC). Preclinical data suggest that pemetrexed may synergistically interact with gemcitabine by enhancing the expression of human equilibrative nucleoside transporter 1 (hENT1) and deoxycytidine kinase (dCK), increasing the uptake and intracellular activation of gemcitabine. A pharmacogenetic approach was adopted to evaluate hENT1 and dCK expressions in humans and to identify the potential best time interval to administer gemcitabine after pemetrexed in patients with advanced NSCLC. METHODS: The dCK and hENT1 expressions, examined by quantitative real-time polymerase chain reaction, were analyzed during each cycle before and at 1, 2, 4, 6, 24, and 48 hours after pemetrexed administration. The relative differences from baseline to each planned time, for peak values and for the relative difference at peak, were measured. RESULTS: Nineteen patients were treated with pemetrexed single agent (500 mg/m every 15 or 21 days). Quantitative real-time polymerase chain reaction analysis revealed a statistically significant (p < 0.001) biphasic increase in both hENT1 and dCK genes at 1 to 2 and 24 to 48 hours after pemetrexed administration. CONCLUSIONS: This is the first evidence of dCK and hENT1 induction by pemetrexed in humans, suggesting that the pemetrexed→gemcitabine combination should be optimized by the administration of gemcitabine 1 to 2 or 24 to 48 hours after pemetrexed. These results support further studies to validate the role of dCK/hENT1 in vivo modulation for the optimization of gemcitabine-pemetrexed combination in patients with NSCLC.