Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations

Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice

Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO and CCFR consortia

Genome-wide association studies (GWAS) have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesized that SNPs previously associated with other cancers may additionally be associated with colorectal cancer. In a large-scale study, we examined 171 SNPs previously associated with 18 different cancers for their associations with colorectal cancer

An evaluation methodology for protocol analysis systems

Current day communication systems rely on protocols to provide secure communications among parties. Weaknesses in protocols, at first thought to be secure, have been found through deep analysis. There are many systems that have been designed to provide a means to test the various security characteristics of communication protocols. We present an evaluation methodology that can be used to evaluate protocol analysis systems based on their scope, correctness, performance, and usability characteristics. We apply portions of the methodology to a set of protocol analysis systems to show the evaluation methodology in action.http://archive.org/details/anevaluationmeth109453596US Navy (USN) author.Approved for public release; distribution is unlimited

Driving Simulation

Recent advances in computing power, computer graphics, and virtual reality systems are leading to important new opportunities for the development and use of driving simulators. These advances in technology are pointing towards a future where human-in-the-loop simulation is increasingly valuable for training, humanfactors research, and virtual prototyping. This paper presents a general literature review of driving simulation, and discusses important components of modern driving simulators. The paper concludes with speculation on the future of driving simulation. INTRODUCTION All driving simulators include four components: . a simulation of the physics of the vehicle model and the road surface . a simulation of the surrounding environment, including other vehicles and their surroundings . a system that enables the operator to interpret the state of the model, e.g., video and audio displays, real or virtual instrument panels, a motion base . control devices, e.g., steering wheel, br..

Ship Anti Ballistic Missile Response (SABR)

Includes supplementary materialBased on public law and Presidential mandate, ballistic missile defense development is a front-burner issue for homeland defense and the defense of U.S. and coalition forces abroad. Spearheaded by the Missile Defense Agency, an integrated ballistic missile defense system was initiated to create a layered defense composed of land-, air-, sea-, and space-based assets. The Ship Anti-Ballistic Response (SABR) Project is a systems engineering approach that suggests a conceptualized system solution to meet the needs of the sea portion of ballistic missile defense in the 2025-2030 timeframe. The system is a unique solution to the sea-based ballistic missile defense issue, combining the use of a railgun interceptor and a conformable aperture skin-of-the-ship radar system

Identification of a common variant with potential pleiotropic effect on risk of inflammatory bowel disease and colorectal cancer.

Although genome-wide association studies (GWAS) have separately identified many genetic susceptibility loci for ulcerative colitis (UC), Crohn's disease (CD) and colorectal cancer (CRC), there has been no large-scale examination for pleiotropy, or shared genetic susceptibility, for these conditions. We used logistic regression modeling to examine the associations of 181 UC and CD susceptibility variants previously identified by GWAS with risk of CRC using data from the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. We also examined associations of significant variants with clinical and molecular characteristics in a subset of the studies. Among 11794 CRC cases and 14190 controls, rs11676348, the susceptibility single nucleotide polymorphism (SNP) for UC, was significantly associated with reduced risk of CRC (P = 7E-05). The multivariate-adjusted odds ratio of CRC with each copy of the T allele was 0.93 (95% CI 0.89-0.96). The association of the SNP with risk of CRC differed according to mucinous histological features (P heterogeneity = 0.008). In addition, the (T) allele was associated with lower risk of tumors with Crohn's-like reaction but not tumors without such immune infiltrate (P heterogeneity = 0.02) and microsatellite instability-high (MSI-high) but not microsatellite stable or MSI-low tumors (P heterogeneity = 0.03). The minor allele (T) in SNP rs11676348, located downstream from CXCR2 that has been implicated in CRC progression, is associated with a lower risk of CRC, particularly tumors with a mucinous component, Crohn's-like reaction and MSI-high. Our findings offer the promise of risk stratification of inflammatory bowel disease patients for complications such as CRC