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

Simulation of groundwater conditions in the upper San Pedro basin for the evaluation of alternative futures

The creation of the groundwater model of the Upper San Pedro Basin included two developmental phases: the creation of a conceptual and numerical model. The creation of the conceptual model was accomplished through the utilization of Geographic Information System (GIS) software, namely Arc View, used primarily to view and create point, line, and polygonal shapes. The creation of a numerical model was accomplished by the infusion of the conceptual model into a 3D finite difference grid used in MODFLOW groundwater software from the U.S. Geological Survey. MODFLOW computes the hydraulic head (water level) for each cell within the grid. The infusion of the two models ( conceptual and numerical) was allowed through the use of Department of Defense Groundwater Modeling System (GMS) software. The time period for groundwater modeling began with predevelopment conditions, or "steady state." Steady state conditions were assumed to exist in 1940. The steady state was used as the initial condition for the subsequent transient analysis. The transient simulation applied historical and current information of pumping stresses to the system from 1940 to 1997. After modeling current conditions, Alternative Futures' scenarios were simulated by modifying current stresses and by adding new ones. The possible future impacts of to the hydro logic system were then evaluated.Digitized from paper copies provided by the Department of Hydrology & Atmospheric Sciences

Optimization of Electrical Geophysical Survey Design for Hydrogeological Applications and Subsurface Target Discrimination

Geophysical imaging methods significantly enhance our knowledge of subsurface characteristics and their use has become prevalent over a range of subsurface investigations. These methods facilitate the detection and characterization of both metallic and nonmetallic subsurface targets, and can provide spatially extensive information on subsurface structure and characteristics that is often impractical to obtain using standard drilling and sampling procedures alone. Electrical imaging methods such as electrical resistivity tomography (ERT) have proven to be particularly useful in hydrogeologic and geotechnical investigations because of the strong dependence of the electrical properties of soils to water saturation, soil texture, and solute concentration. Given the available geophysical tools as well as their applications, the selection of the appropriate geophysical survey design is an essential part of every subsurface geophysical investigation. Where investigations are located in an area with subsurface information already available, this information may be used as a guide for the design of a geophysical survey. In some instances, no subsurface information is available and a survey must be designed to cover a range of possible circumstances. Yet, in other instances, there may be significant subsurface information available, but because of subsurface complexities, a geophysical survey must still be designed to cover a broad range of possibilities. Demonstrating the application and limitations of ERT in a specific field application, the first investigation presented in this document provides guidance for developing methods to improve the design and implementation of ERT surveys in a complex subsurface environment. The two investigations that follow present the development of a relatively simple optimization approach based on limited forward modeling of the geophysical response for both static and mobile surveys. This process is demonstrated through examples of selecting a limited number of ERT surveys to identify and discriminate subsurface target tunnels (with a simple cylindrical geometry). These examples provide insights into the practical application of the optimization process for improved ERT survey design for subsurface target detection. Because of their relative simplicity, the optimization procedures developed here may be used to rapidly identify optimal array configurations without the need for computationally expensive inversion techniques

Simulation of groundwater conditions in the upper San Pedro basin for the evaluation of alternative futures

The creation of the groundwater model of the Upper San Pedro Basin included two developmental phases: the creation of a conceptual and numerical model. The creation of the conceptual model was accomplished through the utilization of Geographic Information System (GIS) software, namely Arc View, used primarily to view and create point, line, and polygonal shapes. The creation of a numerical model was accomplished by the infusion of the conceptual model into a 3D finite difference grid used in MODFLOW groundwater software from the U.S. Geological Survey. MODFLOW computes the hydraulic head (water level) for each cell within the grid. The infusion of the two models ( conceptual and numerical) was allowed through the use of Department of Defense Groundwater Modeling System (GMS) software. The time period for groundwater modeling began with predevelopment conditions, or "steady state." Steady state conditions were assumed to exist in 1940. The steady state was used as the initial condition for the subsequent transient analysis. The transient simulation applied historical and current information of pumping stresses to the system from 1940 to 1997. After modeling current conditions, Alternative Futures' scenarios were simulated by modifying current stresses and by adding new ones. The possible future impacts of to the hydro logic system were then evaluated.Digitized from paper copies provided by the Department of Hydrology & Atmospheric Sciences

Optimization of electrical geophysical survey design for hydrogeological applications and subsurface target discrimination

Geophysical imaging methods significantly enhance our knowledge of subsurface characteristics and their use has become prevalent over a range of subsurface investigations. These methods facilitate the detection and characterization of both metallic and nonmetallic subsurface targets, and can provide spatially extensive information on subsurface structure and characteristics that is often impractical to obtain using standard drilling and sampling procedures alone. Electrical imaging methods such as electrical resistivity tomography (ERT) have proven to be particularly useful in hydrogeologic and geotechnical investigations because of the strong dependence of the electrical properties of soils to water saturation, soil texture, and solute concentration. Given the available geophysical tools as well as their applications, the selection of the appropriate geophysical survey design is an essential part of every subsurface geophysical investigation. Where investigations are located in an area with subsurface information already available, this information may be used as a guide for the design of a geophysical survey. In some instances, no subsurface information is available and a survey must be designed to cover a range of possible circumstances. Yet, in other instances, there may be significant subsurface information available, but because of subsurface complexities, a geophysical survey must still be designed to cover a broad range of possibilities. Demonstrating the application and limitations of ERT in a specific field application, the first investigation presented in this document provides guidance for developing methods to improve the design and implementation of ERT surveys in a complex subsurface environment. The two investigations that follow present the development of a relatively simple optimization approach based on limited forward modeling of the geophysical response for both static and mobile surveys. This process is demonstrated through examples of selecting a limited number of ERT surveys to identify and discriminate subsurface target tunnels (with a simple cylindrical geometry). These examples provide insights into the practical application of the optimization process for improved ERT survey design for subsurface target detection. Because of their relative simplicity, the optimization procedures developed here may be used to rapidly identify optimal array configurations without the need for computationally expensive inversion techniques

Simulation of Groundwater Conditions in the Upper San Pedro Basin for the Evaluation of Alternative Futures

The creation of the groundwater model of the Upper San Pedro Basin included two developmental phases: the creation of a conceptual and numerical model. The creation of the conceptual model was accomplished through the utilization of Geographic Information System (GIS) software, namely ArcView, used primarily to view and create point, line, and polygonal shapes. The creation of a numerical model was accomplished by the infusion of the conceptual model into a 3D finite difference grid used in MODFLOW groundwater software from the U.S. Geological Survey. MODFLOW computes the hydraulic head (water level) for each cell within the grid. The infusion of the two models (conceptual and numerical) was allowed through the use of Department of Defense Groundwater Modeling System (GMS) software. The time period for groundwater modeling began with predevelopment conditions, or "steady state." Steady state conditions were assumed to exist in 1940. The steady state was used as the initial condition for the subsequent transient analysis. The transient simulation applied historical and current information of pumping stresses to the system from 1940 to 1997. After modeling current conditions, Alternative Futures' scenarios were simulated by modifying current stresses and by adding new ones. The possible future impacts of to the hydrologic system were then evaluated.This title from the Hydrology & Water Resources Technical Reports collection is made available by the Department of Hydrology & Atmospheric Sciences and the University Libraries, University of Arizona. If you have questions about titles in this collection, please contact [email protected]