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Investment in the capabilities of the world's 1·2 billion adolescents is vital to the UN's Sustainable Development Agenda. We examined investments in countries of low income, lower-middle income, and upper-middle income covering the majority of these adolescents globally to derive estimates of investment returns given existing knowledge. The costs and effects of the interventions were estimated by adapting existing models and by extending methods to create new modelling tools. Benefits were valued in terms of increased gross domestic product and averted social costs. The initial analysis showed high returns for the modelled interventions, with substantial variation between countries and with returns generally higher in low-income countries than in countries of lower-middle and upper-middle income. For interventions targeting physical, mental, and sexual health (including a human papilloma virus programme), an investment of US$4·6 per capita each year from 2015 to 2030 had an unweighted mean benefit to cost ratio (BCR) of more than 10·0, whereas, for interventions targeting road traffic injuries, a BCR of 5·9 (95% CI 5·8–6·0) was achieved on investment of $0·6 per capita each year. Interventions to reduce child marriage ($3·8 per capita each year) had a mean BCR of 5·7 (95% CI 5·3–6·1), with the effect high in low-income countries. Investment to increase the extent and quality of secondary schooling is vital but will be more expensive than other interventions—investment of $22·6 per capita each year from 2015 to 2030 generated a mean BCR of 11·8 (95% CI 11·6–12·0). Investments in health and education will not only transform the lives of adolescents in resource-poor settings, but will also generate high economic and social returns. These returns were robust to substantial variation in assumptions. Although the knowledge base on the impacts of interventions is limited in many areas, and a major research effort is needed to build a more complete investment framework, these analyses suggest that comprehensive investments in adolescent health and wellbeing should be given high priority in national and international policy.

Australia introduced a human papillomavirus (HPV) vaccination programme with the quadrivalent HPV vaccine for all women aged 12–26 years between 2007 and 2009. We analysed trends in cervical abnormalities in women in Victoria, Australia, before and after introduction of the vaccination programme.

Epidemiologic studies have reported associations between fine particulate air pollution and cardiovascular mortality or hospitalization for cardiac events. However the evidence regarding the association between air pollution and acute cardiac events, such as out-of-hospital cardiac arrest, is inconsistent.

A mutational analysis of the Ras-binding domain (RBD) of c-Raf-1 identified three amino acid positions (Asn64, Ala85, and Val88) where amino acid substitution with basic residues increases the binding of RBD to recombinant v-Ha-Ras. The greatest increase in binding (6–9-fold) was observed with the A85K-RBD mutant. The elevated binding for the A85K-RBD and V88R-RBD mutants was also detected with Ras expressed in cultured mammalian cells, namely NIH-3T3 and BAF cells. None of the wild type residues in RBD positions Asn64, Ala85, and Val88have been previously implicated in the interaction with Ras (Block, C., Janknecht, R., Herrmann, C., Nassar, N., and Wittinghofer, A. (1996)Nat. Struct. Biol.3, 244–251; Nassar, N., Horn, G., Herrmann, C., Scherer, A., McCormick, F., and Wittinghofer, A. (1995)Nature375, 554–560). The discovery of elevated binding among the mutants in these positions implies that additional RBD residues can be used to generate the Ras·RBD complex. These findings are of particular significance in the design of Ras antagonists based on the RBD prototype. The A85K-RBD mutant can be used to develop an assay for measuring the level of activated Ras in cultured cells; Sepharose-linked A85K-RBD·GST fusion protein served as an activation-specific probe to precipitate Ras·GTP but not Ras·GDP from epidermal growth factor-stimulated cells. A85K-RBD precipitates up to 5-fold more Ras·GTP from mammalian cells than wild type RBD.