Impact of Tennessee\u27s Value-added Assessment System on School Superintendents\u27 Decision-making

The problem related to this study was to develop a clearer understanding of the impact of Tennessee\u27s Value-Added Assessment System (TVAAS) on school superintendents\u27 decision-making responsibilities in view of school reform efforts at both the national and state levels during the last decade. The purpose of this study was to identify relationships between three independent variables (superintendents\u27 years of experience, superintendents\u27 perceived degree of personnel acceptance, and superintendents\u27 perceived technical assistance availability for data analysis and interpretation of results) and superintendents perceptions of the system on eight aspects (student learning; teacher performance; school system success; educational accountability; educational equality; assessment decisions; personnel decisions; and, curriculum and professional development decisions). Superintendents in the 139 Tennessee school systems were surveyed using an instrument containing 51 response items. The return rate was 81% (N = 112). Six research questions were answered by analyzing 24 null hypotheses using the chi square test, with Kendall\u27s Tau-B for determining strength of relationships. Hypotheses were tested at the.05 level of significance. All null hypotheses related to superintendents\u27 perceived degree of school personnel acceptance were rejected, with the exception of personnel decisions. All null hypotheses related to superintendents\u27 years of experience were retained. The null hypothesis related to superintendents\u27 perceived TVAAS technical assistance received and educational accountability was rejected. All other null hypotheses related to superintendents\u27 perceived technical assistance availability regarding data analysis and interpretation of value-added assessment results were retained. Results indicated the practice of participatory leadership among Tennessee superintendents. Recommendations included further research to determine possible differences between rural and urban school systems and between elected and appointed superintendents across Tennessee

A "superstorm": When moral panic and new risk discourses converge in the media

This is an Author's Accepted Manuscript of an article published in Health, Risk and Society, 15(6), 681-698, 2013, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/13698575.2013.851180.There has been a proliferation of risk discourses in recent decades but studies of these have been polarised, drawing either on moral panic or new risk frameworks to analyse journalistic discourses. This article opens the theoretical possibility that the two may co-exist and converge in the same scare. I do this by bringing together more recent developments in moral panic thesis, with new risk theory and the concept of media logic. I then apply this theoretical approach to an empirical analysis of how and with what consequences moral panic and new risk type discourses converged in the editorials of four newspaper campaigns against GM food policy in Britain in the late 1990s. The article analyses 112 editorials published between January 1998 and December 2000, supplemented with news stories where these were needed for contextual clarity. This analysis shows that not only did this novel food generate intense media and public reactions; these developed in the absence of the type of concrete details journalists usually look for in risk stories. Media logic is important in understanding how journalists were able to engage and hence how a major scare could be constructed around convergent moral panic and new risk type discourses. The result was a media ‘superstorm’ of sustained coverage in which both types of discourse converged in highly emotive mutually reinforcing ways that resonated in a highly sensitised context. The consequence was acute anxiety, social volatility and the potential for the disruption of policy and social change

HNF1B variants associate with promoter methylation and regulate gene networks activated in prostate and ovarian cancer

Two independent regions within HNF1B are consistently identified in prostate and ovarian cancer genome-wide association studies (GWAS); their functional roles are unclear. We link prostate cancer (PC) risk SNPs rs11649743 and rs3760511 with elevated HNF1B gene expression and allele-specific epigenetic silencing, and outline a mechanism by which common risk variants could effect functional changes that increase disease risk: functional assays suggest that HNF1B is a pro-differentiation factor that suppresses epithelial-to-mesenchymal transition (EMT) in unmethylated, healthy tissues. This tumor-suppressor activity is lost when HNF1B is silenced by promoter methylation in the progression to PC. Epigenetic inactivation of HNF1B in ovarian cancer also associates with known risk SNPs, with a similar impact on EMT. This represents one of the first comprehensive studies into the pleiotropic role of a GWAS-associated transcription factor across distinct cancer types, and is the first to describe a conserved role for a multi-cancer genetic risk factor

HNF1B variants associate with promoter methylation and regulate gene networks activated in prostate and ovarian cancer.

Two independent regions within HNF1B are consistently identified in prostate and ovarian cancer genome-wide association studies (GWAS); their functional roles are unclear. We link prostate cancer (PC) risk SNPs rs11649743 and rs3760511 with elevated HNF1B gene expression and allele-specific epigenetic silencing, and outline a mechanism by which common risk variants could effect functional changes that increase disease risk: functional assays suggest that HNF1B is a pro-differentiation factor that suppresses epithelial-to-mesenchymal transition (EMT) in unmethylated, healthy tissues. This tumor-suppressor activity is lost when HNF1B is silenced by promoter methylation in the progression to PC. Epigenetic inactivation of HNF1B in ovarian cancer also associates with known risk SNPs, with a similar impact on EMT. This represents one of the first comprehensive studies into the pleiotropic role of a GWAS-associated transcription factor across distinct cancer types, and is the first to describe a conserved role for a multi-cancer genetic risk factor

CYP19A1 fine-mapping and Mendelian randomization: estradiol is causal for endometrial cancer.

Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancer and with estradiol (E2) concentrations. We analyzed 2937 single nucleotide polymorphisms (SNPs) in 6608 endometrial cancer cases and 37 925 controls and report the first genome wide-significant association between endometrial cancer and a CYP19A1 SNP (rs727479 in intron 2, P=4.8×10(-11)). SNP rs727479 was also among those most strongly associated with circulating E2 concentrations in 2767 post-menopausal controls (P=7.4×10(-8)). The observed endometrial cancer odds ratio per rs727479 A-allele (1.15, CI=1.11-1.21) is compatible with that predicted by the observed effect on E2 concentrations (1.09, CI=1.03-1.21), consistent with the hypothesis that endometrial cancer risk is driven by E2. From 28 candidate-causal SNPs, 12 co-located with three putative gene-regulatory elements and their risk alleles associated with higher CYP19A1 expression in bioinformatical analyses. For both phenotypes, the associations with rs727479 were stronger among women with a higher BMI (Pinteraction=0.034 and 0.066 respectively), suggesting a biologically plausible gene-environment interaction.Fine-mapping analysis was supported by NHMRC project grant [ID#1031333] to ABS, DFE and AMD. ABS, PW, GWM, and DRN are supported by the NHMRC Fellowship scheme. AMD is supported by the Joseph Mitchell Trust. IT is supported by Cancer Research UK and the Oxford Comprehensive Biomedical Research Centre. Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement no 223175 [HEALTH-F2-2009-223175] [COGS], Cancer Research UK [C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565], the National Institutes of Health [CA128978] and Post-Cancer GWAS initiative [1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative], the Department of Defence [W81XWH-10-1-0341], the Canadian Institutes of Health Research [CIHR] for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. ANECS recruitment was supported by project grants from the NHMRC [ID#339435], The Cancer Council Queensland [ID#4196615] and Cancer Council Tasmania [ID#403031 and ID#457636]. SEARCH recruitment was funded by a programme grant from Cancer Research UK [C490/A10124]. Stage 1 and stage 2 case genotyping was supported by the NHMRC [ID#552402, ID#1031333]. This study 647 makes use of data generated by the Wellcome Trust Case-Control Consortium (WTCCC). A full list of the investigators who contributed to the generation of the data is available from www.wtccc.org.uk. Funding for the project was provided by the Wellcome Trust under award 076113. We acknowledge use of DNA from the British 1958 Birth Cohort collection, funded by the Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02 - funding for this project was provided by the Wellcome Trust under award 085475. NSECG was supported by the EU FP7 CHIBCHA grant and Wellcome Trust Centre for Human Genetics Grant 090532/Z/09Z, and CORGI by Cancer Research UK. Recruitment of the QIMR Berghofer controls was supported by the NHMRC. The University of Newcastle, the Gladys M Brawn Senior Research Fellowship scheme, The Vincent Fairfax Family Foundation, the Hunter Medical Research Institute and the Hunter Area Pathology Service all contributed towards the costs of establishing the Hunter Community Study. The Bavarian Endometrial Cancer Study (BECS) was partly funded by the ELAN fund of the University of Erlangen. The Leuven Endometrium Study (LES) was supported by the Verelst Foundation for endometrial cancer. The Mayo Endometrial Cancer Study (MECS) and Mayo controls (MAY) were supported by grants from the National Cancer Institute of United States Public Health Service [R01 CA122443, P30 CA15083, P50 CA136393, and GAME-ON the NCI Cancer Post-GWAS Initiative U19 CA148112], the Fred C and Katherine B Andersen Foundation, the Mayo Foundation, and the Ovarian Cancer Research Fund with support of the Smith family, in memory of Kathryn Sladek Smith. MoMaTEC received financial support from a Helse Vest Grant, the University of Bergen, Melzer Foundation, The Norwegian Cancer Society (Harald Andersens legat), The Research Council of Norway and Haukeland University Hospital. 672 The Newcastle Endometrial Cancer Study (NECS) acknowledges contributions from the University of Newcastle, The NBN Children’s Cancer Research Group, Ms Jennie Thomas and the Hunter Medical Research Institute. RENDOCAS was supported through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet [numbers: 20110222, 20110483, 20110141 and DF 07015], The Swedish Labor Market Insurance [number 100069] and The Swedish Cancer Society [number 11 0439]. The Cancer Hormone Replacement Epidemiology in Sweden Study (CAHRES, formerly called The Singapore and Swedish Breast/Endometrial Cancer Study; SASBAC) was supported by funding from the Agency for Science, Technology and Research of Singapore (A*STAR), the US National Institutes of Health and the Susan G. Komen Breast Cancer Foundation. The Breast Cancer Association Consortium (BCAC) is funded by Cancer Research UK [C1287/A10118, C1287/A12014]. The Ovarian Cancer Association Consortium (OCAC) is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith [PPD/RPCI.07], and the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge. Additional funding for individual control groups is detailed in the Supplementary Information. EPIC-Norfolk was funded by research programme grant funding from Cancer Research UK and the Medical Research Council with additional support from the Stroke Association, British Heart Foundation, Department of Health, Research into Ageing and Academy of Medical Sciences. The SIBS study was supported by program grant C1287/A10118 and project grants from Cancer Research 697 UK (grant numbers C1287/8459).This is the author accepted manuscript. The final version is available from Bioscientifica via http://dx.doi.org/10.1530/ERC-15-038

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

Shared heritability and functional enrichment across six solid cancers

Correction: Nature Communications 10 (2019): art. 4386 DOI: 10.1038/s41467-019-12095-8Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.Peer reviewe

Shared heritability and functional enrichment across six solid cancers

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis