RESUMO
BACKGROUND: The presence of peer passengers increases teenage drivers' fatal crash risk. Distraction and social influence are the two main factors that have been associated with increased risk. Teen drivers' perceptions of their peer passengers on these factors could inform our understanding of the conditions under which peer passengers increase crash risk or promote safer driving. The purpose of this study was to examine teen drivers' perceptions of their peer passengers on distraction and social influence. METHOD: A convenience sample of male and female drivers participated in a semi-structured interview that included questions on their perceptions of the effects of peer passengers on driving on distraction and social influence. The analysis of the interviews was guided by a grounded theory approach. FINDINGS: Teenage drivers were aware of the risk that peer passengers posed. Some described having passengers in the vehicle as distracting, and recognized that the level of distraction increased with the number of passengers in the vehicle. Drivers that felt responsible for the safety of their peer passengers described strategies they used to control the in-vehicle environment. Drivers described driving with passengers as a performance, and articulated direct and indirect sources of pressure, gender norms, and unspoken expectations of their passengers as influencing their driving behavior. CONCLUSIONS: The influence of passengers is situation specific and dependent on whom the passenger(s) may be. Passenger influence may be either protective or harmful, depending on the circumstances. Some passengers exert direct influence, but often their influence appears more indirect and subtle.
RESUMO
We report the antitumor effects of nitric oxide (NO) releasing derivatives of the PARP-1 inhibitor olaparib (1). Compound 5b was prepared by coupling the carboxyl group of 3b and the free amino group of arylated diazeniumdiolated piperazine 4. Analogue 5a has the same structure except that the F is replaced by H. Compound 13 is the same as 5b except that a Me2N-N(O)âNO- group was added para and ortho to the nitro groups of the dinitrophenyl ring. The resulting prodrugs are activated by glutathione in a reaction accelerated by glutathione S-transferase P1 (GSTP1), an enzyme frequently overexpressed in cancers. This metabolism generates NO plus a PARP-1 inhibitor simultaneously, consuming reducing equivalents, leading to DNA damage concomitant with inhibition of DNA repair, and in the case of 13 inducing cross-linking glutathionylation of proteins. Compounds 5b and 13 reduced the growth rates of A549 human lung adenocarcinoma xenografts with no evidence of systemic toxicity.