410 research outputs found

    A parallel implementation of Davidson methods for large-scale eigenvalue problems in SLEPc

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    In the context of large-scale eigenvalue problems, methods of Davidson type such as Jacobi-Davidson can be competitive with respect to other types of algorithms, especially in some particularly difficult situations such as computing interior eigenvalues or when matrix factorization is prohibitive or highly inefficient. However, these types of methods are not generally available in the form of high-quality parallel implementations, especially for the case of non-Hermitian eigenproblems. We present our implementation of various Davidson-type methods in SLEPc, the Scalable Library for Eigenvalue Problem Computations. The solvers incorporate many algorithmic variants for subspace expansion and extraction, and cover a wide range of eigenproblems including standard and generalized, Hermitian and non-Hermitian, with either real or complex arithmetic. We provide performance results on a large battery of test problems.This work was supported by the Spanish Ministerio de Ciencia e Innovacion under project TIN2009-07519. Author's addresses: E. Romero, Institut I3M, Universitat Politecnica de Valencia, Cami de Vera s/n, 46022 Valencia, Spain), and J. E. Roman, Departament de Sistemes Informatics i Computacio, Universitat Politecnica de Valencia, Cami de Vera s/n, 46022 Valencia, Spain; email: [email protected] Alcalde, E.; Román Moltó, JE. (2014). A parallel implementation of Davidson methods for large-scale eigenvalue problems in SLEPc. ACM Transactions on Mathematical Software. 40(2):13:01-13:29. https://doi.org/10.1145/2543696S13:0113:29402P. Arbenz, M. Becka, R. Geus, U. Hetmaniuk, and T. Mengotti. 2006. On a parallel multilevel preconditioned Maxwell eigensolver. Parallel Comput. 32, 2, 157--165.Z. Bai, J. Demmel, J. Dongarra, A. Ruhe, and H. van der Vorst, Eds. 2000. Templates for the Solution of Algebraic Eigenvalue Problems: A Practical Guide. SIAM, Philadelphia, PA.C. G. Baker, U. L. Hetmaniuk, R. B. Lehoucq, and H. K. Thornquist. 2009. Anasazi software for the numerical solution of large-scale eigenvalue problems. ACM Trans. Math. Softw. 36, 3, 13:1--13:23.S. Balay, J. Brown, K. Buschelman, V. Eijkhout, W. Gropp, D. Kaushik, M. Knepley, L. C. McInnes, B. Smith, and H. Zhang. 2011. PETSc users manual. Tech. Rep. ANL-95/11-Revision 3.2, Argonne National Laboratory.S. Balay, W. D. Gropp, L. C. McInnes, and B. F. Smith. 1997. Efficient management of parallelism in object oriented numerical software libraries. In Modern Software Tools in Scientific Computing, E. Arge, A. M. Bruaset, and H. P. Langtangen, Eds., Birkhaüser, 163--202.M. A. Brebner and J. Grad. 1982. Eigenvalues of Ax =λ Bx for real symmetric matrices A and B computed by reduction to a pseudosymmetric form and the HR process. Linear Algebra Appl. 43, 99--118.C. Campos, J. E. Roman, E. Romero, and A. Tomas. 2011. SLEPc users manual. Tech. Rep. DSICII/24/02 - Revision 3.2, D. Sistemes Informàtics i Computació, Universitat Politècnica de València. http://www.grycap.upv.es/slepc.T. Dannert and F. Jenko. 2005. Gyrokinetic simulation of collisionless trapped-electronmode turbulence. Phys. Plasmas 12, 7, 072309.E. R. Davidson. 1975. The iterative calculation of a few of the lowest eigenvalues and corresponding eigenvectors of large real-symmetric matrices. J. Comput. Phys. 17, 1, 87--94.T. A. Davis and Y. Hu. 2011. The University of Florida Sparse Matrix Collection. ACM Trans. Math. Softw. 38, 1, 1:1--1:25.H. C. Elman, A. Ramage, and D. J. Silvester. 2007. Algorithm 866: IFISS, a Matlab toolbox for modelling incompressible flow. ACM Trans. Math. Softw. 33, 2. Article 14.T. Ericsson and A. Ruhe. 1980. The spectral transformation Lanczos method for the numerical solution of large sparse generalized symmetric eigenvalue problems. Math. Comp. 35, 152, 1251--1268.M. Ferronato, C. Janna, and G. Pini. 2012. Efficient parallel solution to large-size sparse eigenproblems with block FSAI preconditioning. Numer. Linear Algebra Appl. 19, 5, 797--815.D. R. Fokkema, G. L. G. Sleijpen, and H. A. van der Vorst. 1998. Jacobi--Davidson style QR and QZ algorithms for the reduction of matrix pencils. SIAM J. Sci. Comput. 20, 1, 94--125.M. A. Freitag and A. Spence. 2007. Convergence theory for inexact inverse iteration applied to the generalised nonsymmetric eigenproblem. Electron. Trans. Numer. Anal. 28, 40--64.M. Genseberger. 2010. Improving the parallel performance of a domain decomposition preconditioning technique in the Jacobi-Davidson method for large scale eigenvalue problems. App. Numer. Math. 60, 11, 1083--1099.V. Hernandez, J. E. Roman, and A. Tomas. 2007. Parallel Arnoldi eigensolvers with enhanced scalability via global communications rearrangement. Parallel Comput. 33, 7--8, 521--540.V. Hernandez, J. E. Roman, and V. Vidal. 2005. SLEPc: A scalable and flexible toolkit for the solution of eigenvalue problems. ACM Trans. Math. Softw. 31, 3, 351--362.V. Heuveline, B. Philippe, and M. Sadkane. 1997. Parallel computation of spectral portrait of large matrices by Davidson type methods. Numer. Algor. 16, 1, 55--75.M. E. Hochstenbach. 2005a. Generalizations of harmonic and refined Rayleigh-Ritz. Electron. Trans. Numer. Anal. 20, 235--252.M. E. Hochstenbach. 2005b. Variations on harmonic Rayleigh--Ritz for standard and generalized eigenproblems. Preprint, Department of Mathematics, Case Western Reserve University.M. E. Hochstenbach and Y. Notay. 2006. The Jacobi--Davidson method. GAMM Mitt. 29, 2, 368--382.F.-N. Hwang, Z.-H. Wei, T.-M. Huang, and W. Wang. 2010. A parallel additive Schwarz preconditioned Jacobi-Davidson algorithm for polynomial eigenvalue problems in quantum dot simulation. J. Comput. Phys. 229, 8, 2932--2947.A. V. Knyazev. 2001. Toward the optimal preconditioned eigensolver: Locally optimal block preconditioned conjugate gradient method. SIAM J. Sci. Comput. 23, 2, 517--541.A. V. Knyazev, M. E. Argentati, I. Lashuk, and E. E. Ovtchinnikov. 2007. Block Locally Optimal Preconditioned Eigenvalue Xolvers (BLOPEX) in HYPRE and PETSc. SIAM J. Sci. Comput. 29, 5, 2224--2239.J. Kopal, M. Rozložník, M. Tuma, and A. Smoktunowicz. 2012. Rounding error analysis of orthogonalization with a non-standard inner product. Numer. Math. 52, 4, 1035--1058.D. Kressner. 2006. Block algorithms for reordering standard and generalized Schur forms. ACM Trans. Math. Softw. 32, 4, 521--532.R. B. Lehoucq, D. C. Sorensen, and C. Yang. 1998. ARPACK Users' Guide, Solution of Large-Scale Eigenvalue Problems by Implicitly Restarted Arnoldi Methods. SIAM, Philadelphia, PA.Z. Li, Y. Saad, and M. Sosonkina. 2003. pARMS: a parallel version of the algebraic recursive multilevel solver. Numer. Linear Algebra Appl. 10, 5--6, 485--509.J. R. McCombs and A. Stathopoulos. 2006. Iterative validation of eigensolvers: a scheme for improving the reliability of Hermitian eigenvalue solvers. SIAM J. Sci. Comput. 28, 6, 2337--2358.F. Merz, C. Kowitz, E. Romero, J. E. Roman, and F. Jenko. 2012. Multi-dimensional gyrokinetic parameter studies based on eigenvalues computations. Comput. Phys. Commun. 183, 4, 922--930.R. B. Morgan. 1990. Davidson's method and preconditioning for generalized eigenvalue problems. J. Comput. Phys. 89, 241--245.R. B. Morgan. 1991. Computing interior eigenvalues of large matrices. Linear Algebra Appl. 154--156, 289--309.R. B. Morgan and D. S. Scott. 1986. Generalizations of Davidson's method for computing eigenvalues of sparse symmetric matrices. SIAM J. Sci. Statist. Comput. 7, 3, 817--825.R. Natarajan and D. Vanderbilt. 1989. A new iterative scheme for obtaining eigenvectors of large, real-symmetric matrices. J. Comput. Phys. 82, 1, 218--228.M. Nool and A. van der Ploeg. 2000. 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A. van der Vorst. 1996. A Jacobi--Davidson iteration method for linear eigenvalue problems. SIAM J. Matrix Anal. Appl. 17, 2, 401--425.G. L. G. Sleijpen and H. A. van der Vorst. 2000. A Jacobi--Davidson iteration method for linear eigenvalue problems. SIAM Rev. 42, 2, 267--293.G. L. G. Sleijpen, H. A. van der Vorst, and E. Meijerink. 1998. Efficient expansion of subspaces in the Jacobi--Davidson method for standard and generalized eigenproblems. Electron. Trans. Numer. Anal. 7, 75--89.A. Stathopoulos. 2007. Nearly optimal preconditioned methods for Hermitian eigenproblems under limited memory. Part I: Seeking one eigenvalue. SIAM J. Sci. Comput. 29, 2, 481--514.A. Stathopoulos and J. R. McCombs. 2007. Nearly optimal preconditioned methods for Hermitian eigenproblems under limited memory. Part II: Seeking many eigenvalues. SIAM J. Sci. Comput. 29, 5, 2162--2188.A. Stathopoulos and J. R. McCombs. 2010. PRIMME: PReconditioned Iterative MultiMethod Eigensolver: Methods and software description. ACM Trans. Math. Softw. 37, 2, 21:1--21:30.A. Stathopoulos and Y. Saad. 1998. Restarting techniques for the (Jacobi-)Davidson symmetric eigenvalue methods. Electron. Trans. Numer. Anal. 7, 163--181.A. Stathopoulos, Y. Saad, and C. F. Fischer. 1995. Robust preconditioning of large, sparse, symmetric eigenvalue problems. J. Comput. Appl. Math. 64, 3, 197--215.A. Stathopoulos, Y. Saad, and K. Wu. 1998. Dynamic thick restarting of the Davidson, and the implicitly restarted Arnoldi methods. SIAM J. Sci. Comput. 19, 1, 227--245.G. W. Stewart. 2001. Matrix Algorithms. Volume II: Eigensystems. SIAM, Philadelphia, PA.H. A. van der Vorst. 2002. Computational methods for large eigenvalue problems. In Handbook of Numerical Analysis, P. G. Ciarlet and J. L. Lions, Eds., Vol. VIII, Elsevier, 3--179.H. A. van der Vorst. 2004. Modern methods for the iterative computation of eigenpairs of matrices of high dimension. Z. Angew. Math. Mech. 84, 7, 444--451.T. van Noorden and J. Rommes 2007. Computing a partial generalized real Schur form using the Jacobi--Davidson method. Numer. Linear Algebra Appl. 14, 3, 197--215.T. D. Young, E. Romero, and J. E. Roman. 2013. Parallel finite element density functional computations exploiting grid refinement and subspace recycling. Comput. Phys. Commun. 184, 1, 66--72

    Does backreaction enforce the averaged null energy condition in semiclassical gravity?

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    The expected stress-energy tensor of quantum fields generically violates the local positive energy conditions of general relativity. However, may satisfy some nonlocal conditions such as the averaged null energy condition (ANEC), which would rule out traversable wormholes. Although ANEC holds in Minkowski spacetime, it can be violated in curved spacetimes if one is allowed to choose the spacetime and quantum state arbitrarily, without imposition of the semiclassical Einstein equation G_{ab} = 8 \pi . In this paper we investigate whether ANEC holds for solutions to this equation, by studying a free, massless scalar field with arbitrary curvature coupling in perturbation theory to second order about the flat spacetime/vacuum solution. We "reduce the order" of the perturbation equations to eliminate spurious solutions, and consider the limit in which the lengthscales determined by the incoming state are much larger than the Planck length. We also need to assume that incoming classical gravitational radiation does not dominate the first order metric perturbation. We find that although the ANEC integral can be negative, if we average the ANEC integral transverse to the geodesic with a suitable Planck scale smearing function, then a strictly positive result is obtained in all cases except for the flat spacetime/vacuum solution. This result suggests --- in agreement with conclusions drawn by Ford and Roman from entirely independent arguments --- that if traversable wormholes do exist as solutions to the semiclassical equations, they cannot be macroscopic but must be ``Planck scale''. A large portion of our paper is devoted to the analysis of general issues concerning the nature of the semiclassical Einstein equation and of prescriptions for extracting physically relevant solutions.Comment: 54 pages, 3 figures, uses revtex macros and epsf.tex, to appear in Phys Rev D. A new appendix has been added showing consistency of our results with recent results of Visser [gr-qc/9604008]. Some corrections were made to Appendix A, and several other minor changes to the body of the paper also were mad

    Fisheries and Oceanography off Galicia, NW Spain: Mesoscale Spatial and Temporal Changes in Physical Processes and Resultant Patterns of Biological Productivity

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    The Galician shelf off NW Spain (43N degrees 9W degrees) exhibits mesoscale spatial and temporal changes in biological productivity associated with upwelling. Spatial heterogeneity results from local geomorphic and land-sea interactions superimposed on the large scale atmospheric processes that produce upwelling. Wind-induced upwelling events, commonly of short (i.e., week) duration, are more common in the summer than in the winter. A Series of cruises, including some time series sampling, and satellite imagery analysis showed that surface upwelling was more common and persistent on the northern coast compared with the western coast off the coastal embayments, the Rias Bajas. Nearshore off the rias, coastal runoff, which is greater in the rainy winter/spring versus the dry summer, affected upwelling. In early summer, upwelling less often reaches the surface because of increased water column stratification associated with lower surface salinities and thus upwelling is not detected by satellite imagery. Conversely, in late summer, upwelling more often reaches the surface because coastal runoff is reduced during the dry summer months and the water column tends to be less stratified. Plankton biomass and rate processes along the Galician shelf reflected both ambient hydrographic conditions as well as prior history of upwelling or downwelling. Phytoplankton and bacterioplankton were in greatest abundance during upwelling conditions (June through August); in contrast, both zooplankton and fish larvae exhibited highest abundances in March, when there were upwelling conditions prior to our cruise. Spatial differences in the duration and frequency of upwelling events, in combination with advection of water masses, are critical to the patterns of water column productivity and sardine fisheries production off the Galician coast. More persistent upwelling at this NW corner of the Iberian peninsula Supports large sardine fisheries because zooplankton and larval fish populations have time to respond to the higher primary production. Farther down the western Galician coast, the episodic upwelling and resultant intermittent primary production does not support a stable food supply needed to support fisheries. Times series sampling revealed mean response times of bacteria, phytoplankton, and zooplankton to be on the order of a day, days, and weeks, respectively. Sardines showed no spawning response in the relatively short time series sampling. The observed distributional patterns of fish eggs and larvae showed some offshore transport of fish larvae that were spawned inshore during upwelling periods and aggregation of larvae in a convergence zone northwest of Cabo Villano

    Restarted Q-Arnoldi-type methods exploiting symmetry in quadratic eigenvalue problems

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    The final publication is available at Springer via http://dx.doi.org/ 10.1007/s10543-016-0601-5.We investigate how to adapt the Q-Arnoldi method for the case of symmetric quadratic eigenvalue problems, that is, we are interested in computing a few eigenpairs of with M, C, K symmetric matrices. This problem has no particular structure, in the sense that eigenvalues can be complex or even defective. Still, symmetry of the matrices can be exploited to some extent. For this, we perform a symmetric linearization , where A, B are symmetric matrices but the pair (A, B) is indefinite and hence standard Lanczos methods are not applicable. We implement a symmetric-indefinite Lanczos method and enrich it with a thick-restart technique. This method uses pseudo inner products induced by matrix B for the orthogonalization of vectors (indefinite Gram-Schmidt). The projected problem is also an indefinite matrix pair. The next step is to write a specialized, memory-efficient version that exploits the block structure of A and B, referring only to the original problem matrices M, C, K as in the Q-Arnoldi method. This results in what we have called the Q-Lanczos method. Furthermore, we define a stabilized variant analog of the TOAR method. We show results obtained with parallel implementations in SLEPc.This work was supported by the Spanish Ministry of Economy and Competitiveness under Grant TIN2013-41049-P. Carmen Campos was supported by the Spanish Ministry of Education, Culture and Sport through an FPU Grant with reference AP2012-0608.Campos, C.; Román Moltó, JE. (2016). Restarted Q-Arnoldi-type methods exploiting symmetry in quadratic eigenvalue problems. BIT Numerical Mathematics. 56(4):1213-1236. https://doi.org/10.1007/s10543-016-0601-5S12131236564Bai, Z., Su, Y.: SOAR: a second-order Arnoldi method for the solution of the quadratic eigenvalue problem. SIAM J. Matrix Anal. Appl. 26(3), 640–659 (2005)Bai, Z., Day, D., Ye, Q.: ABLE: an adaptive block Lanczos method for non-Hermitian eigenvalue problems. SIAM J. Matrix Anal. Appl. 20(4), 1060–1082 (1999)Bai, Z., Ericsson, T., Kowalski, T.: Symmetric indefinite Lanczos method. In: Bai, Z., Demmel, J., Dongarra, J., Ruhe, A., van der Vorst, H. (eds.) Templates for the solution of algebraic eigenvalue problems: a practical guide, pp. 249–260. Society for Industrial and Applied Mathematics, Philadelphia (2000)Balay, S., Abhyankar, S., Adams, M., Brown, J., Brune, P., Buschelman, K., Dalcin, L., Eijkhout, V., Gropp, W., Kaushik, D., Knepley, M., McInnes, L.C., Rupp, K., Smith, B., Zampini, S., Zhang, H.: PETSc users manual. Tech. Rep. ANL-95/11 - Revision 3.6, Argonne National Laboratory (2015)Benner, P., Faßbender, H., Stoll, M.: Solving large-scale quadratic eigenvalue problems with Hamiltonian eigenstructure using a structure-preserving Krylov subspace method. Electron. Trans. Numer. Anal. 29, 212–229 (2008)Betcke, T., Higham, N.J., Mehrmann, V., Schröder, C., Tisseur, F.: NLEVP: a collection of nonlinear eigenvalue problems. ACM Trans. Math. Softw. 39(2), 7:1–7:28 (2013)Campos, C., Roman, J.E.: Parallel Krylov solvers for the polynomial eigenvalue problem in SLEPc (2015, submitted)Day, D.: An efficient implementation of the nonsymmetric Lanczos algorithm. SIAM J. Matrix Anal. Appl. 18(3), 566–589 (1997)Hernandez, V., Roman, J.E., Vidal, V.: SLEPc: a scalable and flexible toolkit for the solution of eigenvalue problems. ACM Trans. Math. Softw. 31(3), 351–362 (2005)Hernandez, V., Roman, J.E., Tomas, A.: Parallel Arnoldi eigensolvers with enhanced scalability via global communications rearrangement. Parallel Comput. 33(7–8), 521–540 (2007)Jia, Z., Sun, Y.: A refined variant of SHIRA for the skew-Hamiltonian/Hamiltonian (SHH) pencil eigenvalue problem. Taiwan J. Math. 17(1), 259–274 (2013)Kressner, D., Roman, J.E.: Memory-efficient Arnoldi algorithms for linearizations of matrix polynomials in Chebyshev basis. Numer. Linear Algebra Appl. 21(4), 569–588 (2014)Kressner, D., Pandur, M.M., Shao, M.: An indefinite variant of LOBPCG for definite matrix pencils. Numer. Algorithms 66(4), 681–703 (2014)Lancaster, P.: Linearization of regular matrix polynomials. Electron. J. Linear Algebra 17, 21–27 (2008)Lancaster, P., Ye, Q.: Rayleigh-Ritz and Lanczos methods for symmetric matrix pencils. Linear Algebra Appl. 185, 173–201 (1993)Lu, D., Su, Y.: Two-level orthogonal Arnoldi process for the solution of quadratic eigenvalue problems (2012, manuscript)Meerbergen, K.: The Lanczos method with semi-definite inner product. BIT 41(5), 1069–1078 (2001)Meerbergen, K.: The Quadratic Arnoldi method for the solution of the quadratic eigenvalue problem. SIAM J. Matrix Anal. Appl. 30(4), 1463–1482 (2008)Mehrmann, V., Watkins, D.: Structure-preserving methods for computing eigenpairs of large sparse skew-Hamiltonian/Hamiltonian pencils. SIAM J. Sci. Comput. 22(6), 1905–1925 (2001)Parlett, B.N.: The symmetric Eigenvalue problem. Prentice-Hall, Englewood Cliffs (1980) (reissued with revisions by SIAM, Philadelphia)Parlett, B.N., Chen, H.C.: Use of indefinite pencils for computing damped natural modes. Linear Algebra Appl. 140(1), 53–88 (1990)Parlett, B.N., Taylor, D.R., Liu, Z.A.: A look-ahead Lánczos algorithm for unsymmetric matrices. Math. Comput. 44(169), 105–124 (1985)de Samblanx, G., Bultheel, A.: Nested Lanczos: implicitly restarting an unsymmetric Lanczos algorithm. Numer. Algorithms 18(1), 31–50 (1998)Sleijpen, G.L.G., Booten, A.G.L., Fokkema, D.R., van der Vorst, H.A.: Jacobi-Davidson type methods for generalized eigenproblems and polynomial eigenproblems. BIT 36(3), 595–633 (1996)Stewart, G.W.: A Krylov-Schur algorithm for large eigenproblems. 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    National survey of variations in practice in the prevention of surgical site infections in adult cardiac surgery, United Kingdom and Republic of Ireland

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    Background: Currently no national standards exist for the prevention of surgical site infection (SSI) in cardiac surgery. SSI rates range from 1% to 8% between centres. Aim: The aim of this study was to explore and characterize variation in approaches to SSI prevention in the UK and the Republic of Ireland (ROI). Methods: Cardiac surgery centres were surveyed using electronic web-based questionnaires to identify variation in SSI prevention at the level of both institution and consultant teams. Surveys were developed and undertaken through collaboration between the Cardiothoracic Interdisciplinary Research Network (CIRN), Public Health England (PHE) and the National Cardiac Benchmarking Collaborative (NCBC) to encompass routine pre-, intra- and postoperative practice. Findings: Nineteen of 38 centres who were approached provided data and included responses from 139 consultant teams. There was no missing data from those centres that responded. The results demonstrated substantial variation in over 40 aspects of SSI prevention. These included variation in SSI surveillance, reporting of SSI infection rates to external bodies, utilization of SSI risk prediction tools, and the use of interventions such as sternal support devices and gentamicin impregnated sponges. Conclusion: Measured variation in SSI prevention in cardiac centres across the UK and ROI is evidence of clinical uncertainty as to best practice, and has identified areas for quality improvement as well as knowledge gaps to be addressed by future research

    An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

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    For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

    Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

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    SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

    Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

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    Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

    Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

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    Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
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