Socially disinhibited or indiscriminate behavior (IB) has traditionally been investigated using caregiver reports. More recently, an observational measure based on the Strange Situation Procedure (M. Ainsworth, M. Blehar, E. Waters, & S. Wall, 1978), the Rating of Infant and Stranger Engagement (RISE; C. Riley, A. Atlas-Corbett, & K. Lyons-Ruth, 2005), was validated in home-reared at-risk children. The present study aimed to validate the RISE in an institutionally reared sample using the caregiver report, to assess whether IB assessed with the RISE was elevated among the institutionalized children, and to explore potential risk factors associated with IB. The study was conducted among 74 institutionalized toddlers aged 11 to 30 months. Sociodemographic questionnaires were used to assess pre-admission experiences, and aspects of institutional placement were coded from the children’s files in the institution and staff’s report. Institutionalized children displayed high frequencies of IB as assessed on the RISE, and this instrument was validated against caregiver report. Pre-admission experiences of the institutionalized children in their biological families—namely, prenatal risk and maternal emotional neglect risk—predicted IB. Results suggest that the RISE is adequate to use among institutionally reared toddlers and point to aspects of the early familial environment that may be implicated in IB.

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RRM1 is a determinant of gemcitabine efficacy in cancer patients. However, the precision of predicting tumor response based on RRM1 levels is not optimal. We used gene-specific overexpression and RNA interference to assess RRM1's impact on different classes of cytotoxic agents, on drug-drug interactions, and the modulating impact of other molecular and cellular parameters. RRM1 was the dominant determinant of gemcitabine efficacy in various cancer cell lines. RRM1 also impacted the efficacy of other antimetabolite agents. It did not disrupt the interaction of two cytotoxic agents when combined. Cell lines with truncation, deletion, and null status of p53 were resistant to gemcitabine without apparent relationship to RRM1 levels. Pemetrexed and carboplatin sensitivity did not appear to be related to p53 mutation status. The impact of p53 mutations in patients treated with gemcitabine should be studied in prospective clinical trials to develop a model with improved precision of predicting drug efficacy.

a b s t r a c tThe current study extends research on the effects of institutionalization, most notably by examining whether-and how-both pre-institutional maltreatment in the family and the stability and consistency of institutional care interact to shape emotional and behavioral development. Fifty Portuguese children, placed in residential institutions when 8 days to 26 months of age, were evaluated using the Child Behavior Checklist when aged 18-31 months. Caregiver-rated internalizing and externalizing behavior problems proved to be unrelated to both early family and institutional experiences, as main effects, but the interaction of these factors significantly predicted externalizing problems: a history of maltreatment in the family coupled with unstable institutional caregiving arrangements predicted especially elevated levels of externalizing problems. Results are discussed in terms of the importance of more distal and proximate developmental experiences.