Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Variations in state-level definitions: children with special health care needs.

Multiple agencies at the federal and state level provide for children with special health care needs (CSHCN), with variation in eligibility criteria. Epidemiological studies show that 3.8%-32% of children could be classified as children with special health care needs, depending on the definition and method of determination used. OBJECTIVES: To determine the extent of variation between definitions used and funding by Supplemental Security Income (SSI), Title V, and Medicaid for CSHCN. METHODS: Statistics on children receiving SSI and the amount of funding were obtained from the SSI website. This was compared to information on Title V children from the Maternal and Child Health Bureau (MCHB) website and eligibility definitions published by the Institute of Child Health Policy in Gainesville, Florida. Medicaid definitions were obtained through interviews with state Medicaid agencies and confirmed with state regulations. RESULTS: The population enrolled in SSI has varied with alterations in eligibility criteria. The number of children enrolled in SSI and the amount of funding per child in each state correlate with the state poverty rate (r=0.56, p<0.0001; r=0.44, p<0.001). Enrollment in Title V does not correlate with state poverty rates (r=0.16, p=0.25). Title V definitions vary widely among states, but there was no correlation between the number of children served or amount of funding per child and the type of definition used (Z=-0.12, p=0.91; Z=-0.59, p=0.55). State Medicaid agencies rarely define CSHCN. CONCLUSIONS: There is significant variation in definitions used by agencies serving CSHCN. Agencies need to be more explicit with eligibility criteria so the definitions are logical to those making referrals for services

Educating the next generation of pediatricians in urban health care: the Anne E. Dyson Community Pediatrics Training Initiative

To improve the health of children who are exposed to urban health risks, there has been a national recognition of the need for better models of training pediatricians. In 2000, in response to this need, the Dyson Foundation launched a new residents-training model that focuses on community health and advocacy, The Anne E. Dyson Community Pediatrics Training Initiative (the Initiative). The Initiative is made up of 12 programs at ten sites, which are working in their communities to improve the health of the children. At its core are five objectives: to equip residents with tools and knowledge to provide community-based health care, to make use of community resources so that residents learn to practice as medical home providers, to engage residents in the communities in which they work, to develop meaningful partnerships between departments of pediatrics and their communities, and to enhance pediatrics training through interdisciplinary collaborations among schools and departments. Curricular approaches at the participating sites differ slightly, but all have explicitly incorporated teaching community pediatrics into their standard rotations and continuity clinics. The authors showcase the programs of the Initiative and explore how the programs have sought buy-in from their parent institutions, faculty, residents, and communities

The living environment and children's fears following the Indonesian tsunami

The tsunami that struck South-east Asia on 26 December 2004 left more than 500,000 people in Aceh, Indonesia, homeless and displaced to temporary barracks and other communities. This study examines the associations between prolonged habitation in barracks and the nature of fears reported by school-age children and adolescents. In mid-2007, 30 months after the tsunami, the authors interviewed 155 child and parent dyads. Logistic regression analysis was used to compare the fears reported by children and adolescents living in barracks with those reported by their peers who were living in villages. After adjusting for demographic factors and tsunami exposure, the data reveals that children and adolescents living in barracks were three times more likely than those living in villages to report tsunami-related fears. The study demonstrates that continued residence in barracks 30 months after the tsunami is associated with higher rates of reporting tsunami-related fears, suggesting that barracks habitation has had a significant impact on the psychological experience of children and adolescents since the tsunami