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

The archaeology of a late 18th century sealing post in southern Labrador : George Cartwright's 'Stage Cove'

Clarke suggests that text-aided archaeology can "increasingly provide vital experiments in which purely archaeological data may be controlled by documentary data, bearing in mind the inherent biases of both" (1973:18). This thesis uses artifacts and text in order to investigate life at Stage Cove, a small sealing post in southern Labrador. Its occupation during the 1770s by approximately 20 to 30 Anglo-Irish sealers, fishermen, fur trappers, and a few Inuit was documented by George Cartwright, the merchant who managed Stage Cove. His journal contains a wealth of general and specific information on the social and economic structure and operation of this and other late 18th century frontier posts in southern Labrador. Like the journals of many explorers or traders however, it presents a singular view of that social and economic structure tailored for a select audience, apparently the British elite (Cartwright 1792 vol.1:xiii-xvi). -- This thesis compares artifacts and architectural remains recovered during an archaeological excavation of the site in 1986, with Cartwright’s journal and other site documentation. Comparing these independent lines of evidence should provide a more comprehensive interpretation of site activity than would archaeology or the documentary record alone. The degree to which the lines of evidence converge will help strengthen interpretations of the site's history

Partnering to reduce deer-vehicle collisions: improving management of the “deershed”

(a) The problem statement – Nationwide, Deer Vehicle Crashes (DVCs) are killing and injuring more and more people. Each year in the U.S. alone, more than 1.5 million DVCs occur, affecting human safety and resulting in unnecessary social, environmental and economic losses. In addition, insurance companies, drivers and state and federal governments spend upwards of $3 billion each year for the ever-growing number of deer-vehicle collisions. (b) Project objective – Sand County Foundation has constructed a growing partnership to unite interests for an ecological approach to reducing deer-vehicle crashes by: (1) managing the ‘deershed’ rather than engineered corridors, (2) public/private collaboration to implement the most economical and lasting solutions, (3) empowering and providing incentives to landowners willing to contribute to public safety by managing deer populations with human safety, deer herd quality and habitat integrity in mind, (4) monitoring, mapping and adapting management to evolving landscape and transportation trends, (5) providing sound information and support research and education on deer-vehicle crash reduction, (6) leading action to reduce deer-vehicle crashes. (c) Funding source and total budget – private and public entities have contributed to different components of the initial, essential and partnered work. For instance, the Clearinghouse for Deer-Vehicle Collision reduction is a collaboration of the University of Wisconsin, Madison, College of Engineering and State of Wisconsin Department of Transportation with funding derived from state and federal sources. Initiating contributions are approximately$240,000. The initial working group conference to launch this multi-state collaboration included funds from the State of Wisconsin Department of Transportation and the private Bradley Fund for the Environment of Sand County Foundation and had a cost of less than $100,000. Full-fledged operation of this collaboration in five participating states with a sound database and peer-reviewed research activity is projected to cost several million dollars each year. Solutions coming from sound data, better application of meaningful practices and improved ‘deershed’ involvement will be highly cost-effective and will produce considerable co-benefits including reduced crop damage, improvement to native vegetation and less damage to nesting woodland, forest and shrubland bird habitat. (d) Methodology – Assemble a network of stakeholders who will share information, develop solutions and make investments that reduce deer-vehicle crashes. This network will grow in stages, implementing pilot DVC reduction projects in select areas, then adapting and scaling up to regional demonstrations. (e) Summary of findings and their applications – The work to create a sound database for the Upper Mississippi basin states of the U.S. Midwest is well along at the Clearinghouse. The first Working Group Conference of 2000 was well attended by stakeholders from across the Great Lakes’ states and is a springboard to a more advanced session planned for late 2003 or early 2004. Insurance company and transportation leaders are incorporating initial recommendations from scientists associated with the Sand County Foundation and the Clearinghouse into their budget considerations and planning. (f) Implications for future research/policy development – We expect this national network that will link biologists/engineers, state agencies, federal agencies, highway user groups and insurers to achieve better understanding of causes of deer-vehicle crashes, management solutions at the scale of the “deershed” through which highway networks are dispersed and the will to affect change for safer highways. (g) URL for Web site for further information – http://www.sandcounty.ne