A vine copula mixed effect model for trivariate meta-analysis of diagnostic test accuracy studies accounting for disease prevalence

A bivariate copula mixed model has been recently proposed to synthesize diagnostic test accuracy studies and it has been shown that it is superior to the standard generalized linear mixed model in this context. Here, we call trivariate vine copulas to extend the bivariate meta-analysis of diagnostic test accuracy studies by accounting for disease prevalence. Our vine copula mixed model includes the trivariate generalized linear mixed model as a special case and can also operate on the original scale of sensitivity, specificity, and disease prevalence. Our general methodology is illustrated by re-analyzing the data of two published meta-analyses. Our study suggests that there can be an improvement on trivariate generalized linear mixed model in fit to data and makes the argument for moving to vine copula random effects models especially because of their richness, including reflection asymmetric tail dependence, and computational feasibility despite their three dimensionality

Evaluation of rK39 rapid diagnostic tests for canine visceral leishmaniasis : longitudinal study and meta-analysis

Canine visceral leishmaniasis is a vector-borne disease caused by the intracellular parasite Leishmania infantum. It is an important veterinary disease, and dogs are also the main animal reservoir for human infection. The disease is widespread in the Mediterranean area, and parts of Asia and South and Central America, and is potentially fatal in both dogs and humans unless treated. Diagnosis of canine infections requires serological or molecular tests. Detection of infection in dogs is important prior to treatment, and in epidemiological studies and control programmes, and a sensitive and specific rapid diagnostic test would be very useful. Rapid diagnostic tests (RDTs) have been developed, but their diagnostic performance has been reported to be variable. We evaluated the sensitivity of a RDT based on serological detection of the rK39 antigen in a cohort of naturally infected Brazilian dogs. The sensitivity of the test to detect infection was relatively low, but increased with time since infection and the severity of infection. We then carried out a meta-analysis of published studies of rK39 RDTs, evaluating the sensitivity to detect disease and infection. The results suggest that rK39 RDTs may be useful in a veterinary clinical setting, but the sensitivity to detect infection is too low for operational control programmes

Intraneural pseudocyst (so-called ganglion) in an unusual retroperitoneal periadnexal location?

A case of an unusual unilocular cystic lesion of diameter 7 cm located retroperitoneally in the pelvis in close connection to the right adnexa of a 61 year-old woman is presented. Macroscopically, the lesion had a smooth outer and inner surface and was filled with translucent fluid. Histological examination revealed a fibrous and hyalinized wall which lacked a specific lining. Numerous nerve bundles in the cyst wall constituted the most conspicuous element of its histology possibly with some contribution of perineurial and/or mesothelial components. The morphology and immunohistochemistry speak for an intraneural pseudocyst sometimes called intraneural ganglion cyst which is rare in this location

Renormalization group approach to matrix models via noncommutative space

We develop a new renormalization group approach to the large-N limit of matrix models. It has been proposed that a procedure, in which a matrix model of size (N-1) \times (N-1) is obtained by integrating out one row and column of an N \times N matrix model, can be regarded as a renormalization group and that its fixed point reveals critical behavior in the large-N limit. We instead utilize the fuzzy sphere structure based on which we construct a new map (renormalization group) from N \times N matrix model to that of rank N-1. Our renormalization group has great advantage of being a nice analog of the standard renormalization group in field theory. It is naturally endowed with the concept of high/low energy, and consequently it is in a sense local and admits derivative expansions in the space of matrices. In construction we also find that our renormalization in general generates multi-trace operators, and that nonplanar diagrams yield a nonlocal operation on a matrix, whose action is to transport the matrix to the antipode on the sphere. Furthermore the noncommutativity of the fuzzy sphere is renormalized in our formalism. We then analyze our renormalization group equation, and Gaussian and nontrivial fixed points are found. We further clarify how to read off scaling dimensions from our renormalization group equation. Finally the critical exponent of the model of two-dimensional gravity based on our formalism is examined.Comment: 1+42 pages, 4 figure

Matrix theory origins of non-geometric fluxes

We explore the origins of non-geometric fluxes within the context of M theory described as a matrix model. Building upon compactifications of Matrix theory on non-commutative tori and twisted tori, we formulate the conditions which describe compactifications with non-geometric fluxes. These turn out to be related to certain deformations of tori with non-commutative and non-associative structures on their phase space. Quantization of flux appears as a natural consequence of the framework and leads to the resolution of non-associativity at the level of the unitary operators. The quantum-mechanical nature of the model bestows an important role on the phase space. In particular, the geometric and non-geometric fluxes exchange their properties when going from position space to momentum space thus providing a duality among the two. Moreover, the operations which connect solutions with different fluxes are described and their relation to T-duality is discussed. Finally, we provide some insights on the effective gauge theories obtained from these matrix compactifications.Comment: 1+31 pages, reference list update

Candida albicans repetitive elements display epigenetic diversity and plasticity

Transcriptionally silent heterochromatin is associated with repetitive DNA. It is poorly understood whether and how heterochromatin differs between different organisms and whether its structure can be remodelled in response to environmental signals. Here, we address this question by analysing the chromatin state associated with DNA repeats in the human fungal pathogen Candida albicans. Our analyses indicate that, contrary to model systems, each type of repetitive element is assembled into a distinct chromatin state. Classical Sir2-dependent hypoacetylated and hypomethylated chromatin is associated with the rDNA locus while telomeric regions are assembled into a weak heterochromatin that is only mildly hypoacetylated and hypomethylated. Major Repeat Sequences, a class of tandem repeats, are assembled into an intermediate chromatin state bearing features of both euchromatin and heterochromatin. Marker gene silencing assays and genome-wide RNA sequencing reveals that C. albicans heterochromatin represses expression of repeat-associated coding and non-coding RNAs. We find that telomeric heterochromatin is dynamic and remodelled upon an environmental change. Weak heterochromatin is associated with telomeres at 30?°C, while robust heterochromatin is assembled over these regions at 39?°C, a temperature mimicking moderate fever in the host. Thus in C. albicans, differential chromatin states controls gene expression and epigenetic plasticity is linked to adaptation

Results of the MAJORANA DEMONSTRATOR's Search for Double-Beta Decay of 76Ge to Excited States of 76Se

The MAJORANA DEMONSTRATOR is searching for double-beta decay of 76Ge to excited states (E.S.) in 76Se using a modular array of high purity Germanium detectors. 76Ge can decay into three E.S.s of 76Se. The E.S. decays have a clear event signature consisting of a ββ-decay with the prompt emission of one or two γ-rays, resulting in with high probability in a multi-site event. The granularity of the DEMONSTRATOR detector array enables powerful discrimination of this event signature from backgrounds. Using 21.3 kg-y of isotopic exposure, the DEMONSTRATOR has set world leading limits for each E.S. decay, with 90% CL lower half-life limits in the range of (0.56 2.1) ⋅ 1024 y. In particular, for the 2v transition to the first 0+ E.S. of 76Se, a lower half-life limit of 0.68 ⋅ 1024 at 90% CL was achieved

Stringy Stability of Charged Dilaton Black Holes with Flat Event Horizon

Electrically charged black holes with flat event horizon in anti-de Sitter space have received much attention due to various applications in Anti-de Sitter/Conformal Field Theory (AdS/CFT) correspondence, from modeling the behavior of quark-gluon plasma to superconductor. Crucial to the physics on the dual field theory is the fact that when embedded in string theory, black holes in the bulk may become vulnerable to instability caused by brane pair-production. Since dilaton arises naturally in the context of string theory, we study the effect of coupling dilaton to Maxwell field on the stability of flat charged AdS black holes. In particular, we study the stability of Gao-Zhang black holes, which are locally asymptotically anti-de Sitter. We find that for dilaton coupling parameter $\alpha$ > 1, flat black holes are stable against brane pair production, however for 0 < $\alpha$ < 1, the black holes eventually become unstable as the amount of electrical charges is increased. Such instability however, behaves somewhat differently from that of flat Reissner-Nordstr\"om black holes. In addition, we prove that the Seiberg-Witten action of charged dilaton AdS black hole of Gao-Zhang type with flat event horizon (at least in 5-dimension) is always logarithmically divergent at infinity for finite values of $\alpha$, and is finite and positive in the case $\alpha$ tends to infinity . We also comment on the robustness of our result for other charged dilaton black holes that are not of Gao-Zhang type.Comment: Fixed some confusions regarding whether part of the discussions concern electrically charged hole or magnetically charged one. No changes to the result

UNCLES: Method for the identification of genes differentially consistently co-expressed in a specific subset of datasets

Background: Collective analysis of the increasingly emerging gene expression datasets are required. The recently proposed binarisation of consensus partition matrices (Bi-CoPaM) method can combine clustering results from multiple datasets to identify the subsets of genes which are consistently co-expressed in all of the provided datasets in a tuneable manner. However, results validation and parameter setting are issues that complicate the design of such methods. Moreover, although it is a common practice to test methods by application to synthetic datasets, the mathematical models used to synthesise such datasets are usually based on approximations which may not always be sufficiently representative of real datasets. Results: Here, we propose an unsupervised method for the unification of clustering results from multiple datasets using external specifications (UNCLES). This method has the ability to identify the subsets of genes consistently co-expressed in a subset of datasets while being poorly co-expressed in another subset of datasets, and to identify the subsets of genes consistently co-expressed in all given datasets. We also propose the M-N scatter plots validation technique and adopt it to set the parameters of UNCLES, such as the number of clusters, automatically. Additionally, we propose an approach for the synthesis of gene expression datasets using real data profiles in a way which combines the ground-truth-knowledge of synthetic data and the realistic expression values of real data, and therefore overcomes the problem of faithfulness of synthetic expression data modelling. By application to those datasets, we validate UNCLES while comparing it with other conventional clustering methods, and of particular relevance, biclustering methods. We further validate UNCLES by application to a set of 14 real genome-wide yeast datasets as it produces focused clusters that conform well to known biological facts. Furthermore, in-silico-based hypotheses regarding the function of a few previously unknown genes in those focused clusters are drawn. Conclusions: The UNCLES method, the M-N scatter plots technique, and the expression data synthesis approach will have wide application for the comprehensive analysis of genomic and other sources of multiple complex biological datasets. Moreover, the derived in-silico-based biological hypotheses represent subjects for future functional studies.The National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0310-1004)