McGill University

About: McGill University is a education organization based out in Montreal, Quebec, Canada. It is known for research contribution in the topics: Population & Context (language use). The organization has 72688 authors who have published 162565 publications receiving 6966523 citations. The organization is also known as: Royal institution of advanced learning & University of McGill College.

Human papillomavirus DNA versus Papanicolaou screening tests for cervical cancer.

Abstract: Background To determine whether testing for DNA of oncogenic human papillomaviruses (HPV) is superior to the Papanicolaou (Pap) test for cervical-cancer screening, we conducted a randomized trial comparing the two methods. Methods We compared HPV testing, using an assay approved by the Food and Drug Administration, with conventional Pap testing as a screening method to identify high-grade cervical intraepithelial neoplasia in women ages 30 to 69 years in Montreal and St. John's, Canada. Women with abnormal Pap test results or a positive HPV test (at least 1 pg of high-risk HPV DNA per milliliter) underwent colposcopy and biopsy, as did a random sample of women with negative tests. Sensitivity and specificity estimates were corrected for verification bias. Results A total of 10,154 women were randomly assigned to testing. Both tests were performed on all women in a randomly assigned sequence at the same session. The sensitivity of HPV testing for cervical intraepithelial neoplasia of grade 2 or 3 was 94.6%...

Large Population Stochastic Dynamic Games: Closed-Loop McKean-Vlasov Systems and the Nash Certainty Equivalence Principle

Abstract: We consider stochastic dynamic games in large population conditions where multiclass agents are weakly coupled via their individual dynamics and costs. We approach this large population game problem by the so-called Nash Certainty Equivalence (NCE) Principle which leads to a decentralized control synthesis. The McKean-Vlasov NCE method presented in this paper has a close connection with the statistical physics of large particle systems: both identify a consistency relationship between the individual agent (or particle) at the microscopic level and the mass of individuals (or particles) at the macroscopic level. The overall game is decomposed into (i) an optimal control problem whose Hamilton-Jacobi-Bellman (HJB) equation determines the optimal control for each individual and which involves a measure corresponding to the mass effect, and (ii) a family of McKean-Vlasov (M-V) equations which also depend upon this measure. We designate the NCE Principle as the property that the resulting scheme is consistent (or soluble), i.e. the prescribed control laws produce sample paths which produce the mass effect measure. By construction, the overall closed-loop behaviour is such that each agent’s behaviour is optimal with respect to all other agents in the game theoretic Nash sense.

Progression to Malignancy in the Polyoma Middle T Oncoprotein Mouse Breast Cancer Model Provides a Reliable Model for Human Diseases

Abstract: Animal models are powerful tools to analyze the mechanism of the induction of human breast cancer. Here we report a detailed analysis of mammary tumor progression in one mouse model of breast cancer caused by expression of the polyoma middle T oncoprotein (PyMT) in the mammary epithelium, and its comparison to human breast tumors. In PyMT mice, four distinctly identifiable stages of tumor progression from premalignant to malignant stages occur in a single primary tumor focus and this malignant transition is followed by a high frequency of distant metastasis. These stages are comparable to human breast diseases classified as benign or in situ proliferative lesions to invasive carcinomas. In addition to the morphological similarities with human breast cancer, the expression of biomarkers in PyMT-induced tumors is also consistent with those associated with poor outcome in humans. These include a loss of estrogen and progesterone receptors as well as integrin-beta1 expression and the persistent expression of ErbB2/Neu and cyclinD1 in PyMT-induced tumors as they progress to the malignant stage. An increased leukocytic infiltration was also closely associated with the malignant transition. This study demonstrates that the PyMT mouse model is an excellent one to understand the biology of tumor progression in humans.

The Biogeochemical Cycles of Trace Metals in the Oceans

Abstract: Planktonic uptake of some essential metals results in extraordinarily low concentrations in surface seawater. To sequester or take up these micronutrients, various microorganisms apparently release strong complexing agents and catalyze redox reactions that modify the bioavailability of trace metals and promote their rapid cycling in the upper water column. In turn, the low availability of some metals controls the rate of photosynthesis in parts of the oceans and the transformation and uptake of major nutrients such as nitrogen. The extremely low concentrations of several essential metals are both the cause and the result of ultraefficient uptake systems in the plankton and of widespread replacement of metals by one another for various biochemical functions.

An atlas of genetic influences on human blood metabolites

Abstract: Genome-wide association scans with high-throughput metabolic profiling provide unprecedented insights into how genetic variation influences metabolism and complex disease. Here we report the most comprehensive exploration of genetic loci influencing human metabolism thus far, comprising 7,824 adult individuals from 2 European population studies. We report genome-wide significant associations at 145 metabolic loci and their biochemical connectivity with more than 400 metabolites in human blood. We extensively characterize the resulting in vivo blueprint of metabolism in human blood by integrating it with information on gene expression, heritability and overlap with known loci for complex disorders, inborn errors of metabolism and pharmacological targets. We further developed a database and web-based resources for data mining and results visualization. Our findings provide new insights into the role of inherited variation in blood metabolic diversity and identify potential new opportunities for drug development and for understanding disease.