Social-Emotional Difficulties in Irish Children Aged Five and Nine Years: A National, Longitudinal Study.

A small proportion of children experience social-emotional difficulties from early childhood onwards. Longitudinal studies with nationally representative samples are needed to identify the prevalence and the characteristics of children and families persistently experiencing these difficulties. Secondary analysis of data collected on over 7500 Irish children and with the Strengths and Difficulties Questionnaire as the primary indicator, found that 6% of children when they were five year olds and 8% when they were nine-years, had above threshold scores that warranted further investigation. A smaller proportion-2.9% had elevated scores at both ages. Logistic regression analyses found that children with one or more developmental disabilities were up to six times more likely to have sustained difficulties. There were also significant associations with the lower education attainment of primary caregivers and the socio-economic deprivation of families. Primary caregivers and teachers reported higher conflict in their relationships with these children. Although the number of Irish children presenting with continuing social-emotional difficulties is small, they can present an ongoing and future societal cost in terms of the impact on family relations and demands placed on educational, health and social services. This study identified the children and families who are at greatest risk and for whom targeted early intervention services could be provided.

Changes in Children's Speech and Language Difficulties from Age Five to Nine: An Irish National, Longitudinal Study.

In many countries, information on the prevalence of persistent speech and language disorders in early childhood is sparse due to the lack of nationally representative samples and longitudinal studies. Secondary analysis of data collected on over 7500 Irish children at ages 5 and 9 years, found that the prevalence of speech and language difficulties reported by the primary caregivers of Irish children decreased from one in six at age 5 to one in 12 at age 9. However, one in 20 children were reported to have difficulties at both ages. Regression analysis compared children with difficulties at both age 5 and age 9 to those who had been reported to have them at age 5 but no longer had such difficulties at age 9. Children with speech and language difficulties at both age 5 and age 9 were more likely to have two or more developmental impairments as well as current or past hearing impairments. Teachers and parents also reported a greater number of social-emotional difficulties. Family characteristics did not differ significantly across the two groupings. At best, up to one third of the children at ages 5 and 9 with speech and language difficulties had two or more contacts with a speech and language therapists in the preceding 12 month period. Increased support to these children, their parents and teachers would seem to be warranted.

A Phase I Trial of Combined Ridaforolimus and MK-2206 in Patients with Advanced Malignancies.

PURPOSE: The PI3K/Akt/mTOR signaling pathway is aberrantly activated in many cancers. Combining ridaforolimus, an mTOR inhibitor, with MK-2206, an Akt inhibitor, may more completely block the PI3K pathway and inhibit tumor growth. EXPERIMENTAL DESIGN: This phase I study assessed dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) for the combination of oral ridaforolimus plus oral MK-2206 in patients with advanced solid tumors. Efficacy was evaluated in patients with biomarker-identified estrogen receptor-positive breast cancer (low RAS gene signature and high Ki67 index) or castration-resistant prostate cancer (PTEN deficiency) with PI3K pathway addiction. RESULTS: Thirty-five patients were enrolled: 11 patients in part A (three breast cancer) and 24 biomarker-eligible patients in part B (16 breast cancer, eight prostate cancer). One patient with breast cancer from part A was also found to be biomarker-eligible when tested after she had clinical response. The MTD was 10 mg/d ridaforolimus 5 d/wk + 90 mg/wk MK-2206; 1 of 17 patients experienced DLT (grade 3 rash) at this dose. The most common adverse events at MTD were rash (44.4%), stomatitis (38.9%), diarrhea (27.8%), and decreased appetite (27.8%). By investigator assessment, 2 of 16 (12.5%) evaluable patients with breast cancer had partial response; by central assessment, 2 of 14 (14.3%) evaluable patients had complete response. Two patients had durable stable disease (SD) for 416 and 285 days, respectively. No patients with prostate cancer responded; one patient had SD for ≥ 6 months. CONCLUSIONS: Combination ridaforolimus and MK-2206 showed promising activity and good tolerability in heavily pretreated patients with hormone-positive and -negative breast cancer exhibiting PI3K pathway dependence.