Adjusting ROC curve for Covariates with AROC R package

The ability of a medical test to differentiate between diseased and non-diseased states is of vital importance and must be screened by statistical analysis for reliability and improvement. The receiver operating characteristic (ROC) curve remains a popular method of marker analysis, disease screening and diagnosis. Covariates in this field related to the subject’s characteristics are incorporated in the analysis to avoid bias. The covariate adjusted ROC (AROC) curve was proposed as a method of incorporation. The AROC R-package was recently released and brings various methods of estimation based on multiple authors work. The aim of this study was to explore the AROC package functionality and usability using real data noting its possible limitations. The main methods of the package were capable of incorporating different and multiple variables, both categorical and continuous, in the AROC curve estimation. When tested for the same data, AROC curves are generated with no statistical differences, regardless of method. The package offers a variety of methods to estimate the AROC curve complemented with predictive checks and pooled ROC estimation. The package offers a way to conduct a more thorough ROC and AROC analysis, making it available for any R user.This work has been supported by FCT - Fundação para a Ciência e Tecnologia within the R&D Units Project Scope: UIDB/00319/202

Localization of supersymmetric field theories on non-compact hyperbolic three-manifolds

We study supersymmetric gauge theories with an R-symmetry, defined on non-compact, hyperbolic, Riemannian three-manifolds, focusing on the case of a supersymmetry-preserving quotient of Euclidean AdS$_3$. We compute the exact partition function in these theories, using the method of localization, thus reducing the problem to the computation of one-loop determinants around a supersymmetric locus. We evaluate the one-loop determinants employing three different techniques: an index theorem, the method of pairing of eigenvalues, and the heat kernel method. Along the way, we discuss aspects of supersymmetry in manifolds with a conformal boundary, including supersymmetric actions and boundary conditions.Comment: v3:79p, minor clarifications and references adde

Comments on Chern-Simons Contact Terms in Three Dimensions

We study contact terms of conserved currents and the energy-momentum tensor in three-dimensional quantum field theory. They are associated with Chern-Simons terms for background fields. While the integer parts of these contact terms are ambiguous, their fractional parts are meaningful physical observables. In N=2 supersymmetric theories with a U(1)_R symmetry some of these observables lead to an anomaly. Moreover, they can be computed exactly using localization, leading to new tests of dualities.Comment: 37 pages, 3 figures; minor change

N = 2 supersymmetric sigma-models and duality

For two families of four-dimensional off-shell N = 2 supersymmetric nonlinear sigma-models constructed originally in projective superspace, we develop their formulation in terms of N = 1 chiral superfields. Specifically, these theories are: (i) sigma-models on cotangent bundles T*M of arbitrary real analytic Kaehler manifolds M; (ii) general superconformal sigma-models described by weight-one polar supermultiplets. Using superspace techniques, we obtain a universal expression for the holomorphic symplectic two-form \omega^{(2,0)} which determines the second supersymmetry transformation and is associated with the two complex structures of the hyperkaehler space T*M that are complimentary to the one induced from M. This two-form is shown to coincide with the canonical holomorphic symplectic structure. In the case (ii), we demonstrate that \omega^{(2,0)} and the homothetic conformal Killing vector determine the explicit form of the superconformal transformations. At the heart of our construction is the duality (generalized Legendre transform) between off-shell N = 2 supersymmetric nonlinear sigma-models and their on-shell N = 1 chiral realizations. We finally present the most general N = 2 superconformal nonlinear sigma-model formulated in terms of N = 1 chiral superfields. The approach developed can naturally be generalized in order to describe 5D and 6D superconformal nonlinear sigma-models in 4D N = 1 superspace.Comment: 31 pages, no figures; V2: reference and comments added, typos corrected; V3: more typos corrected, published versio

Off-shell superconformal nonlinear sigma-models in three dimensions

We develop superspace techniques to construct general off-shell N=1,2,3,4 superconformal sigma-models in three space-time dimensions. The most general N=3 and N=4 superconformal sigma-models are constructed in terms of N=2 chiral superfields. Several superspace proofs of the folklore statement that N=3 supersymmetry implies N=4 are presented both in the on-shell and off-shell settings. We also elaborate on (super)twistor realisations for (super)manifolds on which the three-dimensional N-extended superconformal groups act transitively and which include Minkowski space as a subspace.Comment: 67 pages; V2: typos corrected, one reference added, version to appear on JHE

Simple rules can guide whether land or ocean based conservation will best benefit marine ecosystems

Coastal marine ecosystems can be managed by actions undertaken both on the land and in the ocean. Quantifying and comparing the costs and benefits of actions in both realms is therefore necessary for efficient management. Here, we quantify the link between terrestrial sediment run-off and a downstream coastal marine ecosystem, and contrast the cost-effectiveness of marine and land-based conservation actions. We use a dynamic land- and sea-scape model to determine whether limited funds should be directed to one of four alternative conservation actions – protection on land, protection in the ocean, restoration on land, or restoration in the ocean – to maximise the extent of light-dependent marine benthic habitats, across decadal time-scales. We apply the model to a case study seagrass meadow in Australia. We find that marine restoration is the most cost-effective action over decadal time-scales in this system, based on a conservative estimate of the rate at which seagrass can expand into new habitat. The optimal decision will vary in different social-ecological contexts, but some basic information can guide optimal investments to counteract land and ocean based stressors: (1) marine restoration should be prioritised if the rates of marine ecosystem decline and expansion are similar and low; (2) marine protection should take precedence if the rate of marine ecosystem decline is high, or if the adjacent catchment is relatively intact and has a low rate of vegetation decline; (3) land-based actions are optimal when the ratio of marine ecosystem expansion to decline is >1.4, with terrestrial restoration typically the most cost effective; and (4) land protection should be prioritised if the catchment is relatively intact, but the rate of vegetation decline is high. These rules-of-thumb illustrate how cost-effective conservation outcomes for connected land-ocean systems can proceed without complex modelling

Cancer Genes Hypermethylated in Human Embryonic Stem Cells

Developmental genes are silenced in embryonic stem cells by a bivalent histone-based chromatin mark. It has been proposed that this mark also confers a predisposition to aberrant DNA promoter hypermethylation of tumor suppressor genes (TSGs) in cancer. We report here that silencing of a significant proportion of these TSGs in human embryonic and adult stem cells is associated with promoter DNA hypermethylation. Our results indicate a role for DNA methylation in the control of gene expression in human stem cells and suggest that, for genes repressed by promoter hypermethylation in stem cells in vivo, the aberrant process in cancer could be understood as a defect in establishing an unmethylated promoter during differentiation, rather than as an anomalous process of de novo hypermethylation

Allosteric Analysis of Glucocorticoid Receptor-DNA Interface Induced by Cyclic Py-Im Polyamide: A Molecular Dynamics Simulation Study

Background: It has been extensively developed in recent years that cell-permeable small molecules, such as polyamide, can be programmed to disrupt transcription factor-DNA interfaces and can silence aberrant gene expression. For example, cyclic pyrrole-imidazole polyamide that competes with glucocorticoid receptor (GR) for binding to glucocorticoid response elements could be expected to affect the DNA dependent binding by interfering with the protein-DNA interface. However, how such small molecules affect the transcription factor-DNA interfaces and gene regulatory pathways through DNA structure distortion is not fully understood so far. Methodology/Principal Findings: In the present work, we have constructed some models, especially the ternary model of polyamides+DNA+GR DNA-binding domain (GRDBD) dimer, and carried out molecular dynamics simulations and free energy calculations for them to address how polyamide molecules disrupt the GRDBD and DNA interface when polyamide and protein bind at the same sites on opposite grooves of DNA. Conclusions/Significance: We found that the cyclic polyamide binding in minor groove of DNA can induce a large structural perturbation of DNA, i.e. a.4 A ˚ widening of the DNA minor groove and a compression of the major groove by more than 4A ˚ as compared with the DNA molecule in the GRDBD dimer+DNA complex. Further investigations for the ternary system of polyamides+DNA+GRDBD dimer and the binary system of allosteric DNA+GRDBD dimer revealed that the compression o