Examining the Systemic Effects of Relational Trust and Network Trustworthiness on School Community: A Multi-Site Case Study of Three Independent Schools

Within the broader context of accountability imposed from beyond our schools, this mixed methods, multi-site case study investigated the development of relational trust and trustworthy relationships as internal accountability structures within three independent schools replicating responsible independence on the scale of the school as trustworthy freedom on the scale of the individual. Interviews, observations, artifacts, sociograms, and surveys were analyzed to identify teacher and administrator perceptions of structures supporting relational trust, accountability to community standards, and sustainable trust-based cultures. Survey data were also analyzed for corresponding evidence of organizational conditions associated with school improvement: teacher orientation to innovation, teacher commitment to school community, peer collaboration, reflective dialog, collective responsibility, focus on student learning, and teacher socialization. Structures found to support responsible freedom at these schools included their historic honor systems, programs for character education, strategic planning, and policies and schedules guiding daily life. Neither structure nor freedom alone was found to be sufficient to sustain cultures built on relational trust and mutual accountability. Inflexible structures or inauthentic, coercive, or incompetent leaders diminished social capital over time at all three schools. Schools enjoying the best organizational conditions for school improvement built capacity by fostering macro-micro feedback loops of honor and trust between the scales of the individual and the school as a professional learning community. Findings were applied to develop a model for individual and organizational capacity building, relating the dimensions of relational trust and accountability to standards. The two-dimensional model for capacity building identified four categories of school capacity based on levels of both relational trust and accountability to standards: low capacity schools, compliant schools, complacent schools, and high capacity schools. The model further developed associated strategies for moving schools in each category towards developing or sustaining high capacity

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

Multiple loci on 8q24 associated with prostate cancer susceptibility

Previous studies have identified multiple loci on 8q24 associated with prostate cancer risk. We performed a comprehensive analysis of SNP associations across 8q24 by genotyping tag SNPs in 5,504 prostate cancer cases and 5,834 controls. We confirmed associations at three previously reported loci and identified additional loci in two other linkage disequilibrium blocks (rs1006908: per-allele OR = 0.87, P = 7.9 x 10(-8); rs620861: OR = 0.90, P = 4.8 x 10(-8)). Eight SNPs in five linkage disequilibrium blocks were independently associated with prostate cancer susceptibility

Identification of seven new prostate cancer susceptibility loci through a genome-wide association study

Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. To identify common PrCa susceptibility alleles, we have previously conducted a genome-wide association study in which 541, 129 SNPs were genotyped in 1,854 PrCa cases with clinically detected disease and 1,894 controls. We have now evaluated promising associations in a second stage, in which we genotyped 43,671 SNPs in 3,650 PrCa cases and 3,940 controls, and a third stage, involving an additional 16,229 cases and 14,821 controls from 21 studies. In addition to previously identified loci, we identified a further seven new prostate cancer susceptibility loci on chromosomes 2, 4, 8, 11, and 22 (P=1.6×10−8 to P=2.7×10−33)