Modelling multivariate disease rates with a latent structure mixture model

Copyright © 2013 SAGE / Statistical Modeling SocietyThere has been considerable recent interest in multivariate modelling of the geographical distribution of morbidity or mortality rates for potentially related diseases. The motivations for this include investigation of similarities or dissimilarities in the risk distribution for the different diseases, as well as ‘borrowing strength’ across disease rates to shrink the uncertainty in geographical risk assessment for any particular disease. A number of approaches to such multivariate modelling have been suggested and this paper proposes an extension to these which may provide a richer range of dependency structures than those encompassed so far. We develop a model which incorporates a discrete mixture of latent structures and argue that this provides potential to represent an enhanced range of correlation structures between diseases at the same time as implicitly allowing for less restrictive spatial correlation structures between geographical units. We compare and contrast our approach to other commonly used multivariate disease models and demonstrate comparative results using data taken from cancer registries on four carcinomas in some 300 geographical units in England, Scotland and Wales

Defining the molecular pathology of pancreatic body and tail adenocarcinom

Background: Pancreatic ductal adenocarcinoma (PDAC) remains a dismal disease, with very little improvement in survival over the past 50 years. Recent large-scale genomic studies have improved understanding of the genomic and transcriptomic landscape of the disease, yet very little is known about molecular heterogeneity according to tumour location in the pancreas; body and tail PDACs especially tend to have a significantly worse prognosis. The aim was to investigate the molecular differences between PDAC of the head and those of the body and tail of the pancreas. Methods: Detailed correlative analysis of clinicopathological variables, including tumour location, genomic and transcriptomic data, was performed using the Australian Pancreatic Cancer Genome Initiative (APGI) cohort, part of the International Cancer Genome Consortium study. Results: Clinicopathological data were available for 518 patients recruited to the APGI, of whom 421 underwent genomic analyses; 179 of these patients underwent whole-genome and 96 RNA sequencing. Patients with tumours of the body and tail had significantly worse survival than those with pancreatic head tumours (12·1 versus 22·0 months; P = 0·001). Location in the body and tail was associated with the squamous subtype of PDAC. Body and tail PDACs enriched for gene programmes involved in tumour invasion and epithelial-to-mesenchymal transition, as well as features of poor antitumour immune response. Whether this is due to a molecular predisposition from the outset, or reflects a later time point on the tumour molecular clock, requires further investigation using well designed prospective studies in pancreatic cancer. Conclusion: PDACs of the body and tail demonstrate aggressive tumour biology that may explain worse clinical outcomes

Resonant Absorption as Mode Conversion?

Resonant absorption and mode conversion are both extensively studied mechanisms for wave "absorption" in solar magnetohydrodynamics (MHD). But are they really distinct? We re-examine a well-known simple resonant absorption model in a cold MHD plasma that places the resonance inside an evanescent region. The normal mode solutions display the standard singular resonant features. However, these same normal modes may be used to construct a ray bundle which very clearly undergoes mode conversion to an Alfv\'en wave with no singularities. We therefore conclude that resonant absorption and mode conversion are in fact the same thing, at least for this model problem. The prime distinguishing characteristic that determines which of the two descriptions is most natural in a given circumstance is whether the converted wave can provide a net escape of energy from the conversion/absorption region of physical space. If it cannot, it is forced to run away in wavenumber space instead, thereby generating the arbitrarily small scales in situ that we recognize as fundamental to resonant absorption and phase mixing. On the other hand, if the converted wave takes net energy way, singularities do not develop, though phase mixing may still develop with distance as the wave recedes.Comment: 23 pages, 8 figures, 2 tables; accepted by Solar Phys (July 9 2010

Conformal Invariance, Dark Energy, and CMB Non-Gaussianity

In addition to simple scale invariance, a universe dominated by dark energy naturally gives rise to correlation functions possessing full conformal invariance. This is due to the mathematical isomorphism between the conformal group of certain 3 dimensional slices of de Sitter space and the de Sitter isometry group SO(4,1). In the standard homogeneous isotropic cosmological model in which primordial density perturbations are generated during a long vacuum energy dominated de Sitter phase, the embedding of flat spatial sections in de Sitter space induces a conformal invariant perturbation spectrum and definite prediction for the shape of the non-Gaussian CMB bispectrum. In the case in which the density fluctuations are generated instead on the de Sitter horizon, conformal invariance of the horizon embedding implies a different but also quite definite prediction for the angular correlations of CMB non-Gaussianity on the sky. Each of these forms for the bispectrum is intrinsic to the symmetries of de Sitter space and in that sense, independent of specific model assumptions. Each is different from the predictions of single field slow roll inflation models which rely on the breaking of de Sitter invariance. We propose a quantum origin for the CMB fluctuations in the scalar gravitational sector from the conformal anomaly that could give rise to these non-Gaussianities without a slow roll inflaton field, and argue that conformal invariance also leads to the expectation for the relation n_S-1=n_T between the spectral indices of the scalar and tensor power spectrum. Confirmation of this prediction or detection of non-Gaussian correlations in the CMB of one of the bispectral shape functions predicted by conformal invariance can be used both to establish the physical origins of primordial density fluctuations and distinguish between different dynamical models of cosmological vacuum dark energy.Comment: 73 pages, 9 figures. Final Version published in JCAP. New Section 4 added on linearized scalar gravitational potentials; New Section 8 added on gravitational wave tensor perturbations and relation of spectral indices n_T = n_S -1; Table of Contents added; Eqs. (3.14) and (3.15) added to clarify relationship of bispectrum plotted to CMB measurements; Some other minor modification

ADAM12 is a circulating marker for stromal activation in pancreatic cancer and predicts response to chemotherapy

Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma that harbors tumor-promoting properties. No good biomarkers exist to monitor the effect of stromal targeting therapies or to predict response. We set out to identify such non-invasive markers for PDAC stroma and predict response to therapy. Gene expression datasets, co-culture experiments, xenografts, and patient samples were analyzed. Serum samples were measured from a cohort of 58 resected patients, and 87 metastatic or locally advanced PDAC patients. Baseline and follow-up levels were assessed in 372 additional metastatic PDAC patients who received nab-paclitaxel with gemcitabine (n = 184) or gemcitabine monotherapy (n = 188) in the phase III MPACT trial. Increased levels of ADAM12 were found in PDAC patients compared to healthy controls (p < 0.0001, n = 157 and n = 38). High levels of ADAM12 significantly associated with poor outcome in resected PDAC (HR 2.07, p = 0.04). In the MPACT trial survival was significantly longer for patients who received nab-paclitaxel and had undetectable ADAM12 levels before treatment (OS 12.3 m vs 7.9 m p = 0.0046). Consistently undetectable or decreased ADAM12 levels during treatment significantly associated with longer survival as well (OS 14.4 m and 11.2 m, respectively vs 8.3, p = 0.0054). We conclude that ADAM12 is a blood-borne proxy for stromal activation, the levels of which have prognostic significance and correlate with treatment benefit

Testing "microscopic" theories of glass-forming liquids

We assess the validity of "microscopic" approaches of glass-forming liquids based on the sole k nowledge of the static pair density correlations. To do so we apply them to a benchmark provided by two liquid models that share very similar static pair density correlation functions while disp laying distinct temperature evolutions of their relaxation times. We find that the approaches are unsuccessful in describing the difference in the dynamical behavior of the two models. Our study is not exhausti ve, and we have not tested the effect of adding corrections by including for instance three-body density correlations. Yet, our results appear strong enough to challenge the claim that the slowd own of relaxation in glass-forming liquids, for which it is well established that the changes of the static structure factor with temperature are small, can be explained by "microscopic" appr oaches only requiring the static pair density correlations as nontrivial input.Comment: 10 pages, 7 figs; Accepted to EPJE Special Issue on The Physics of Glasses. Arxiv version contains an addendum to the appendix which does not appear in published versio

Breed, age and gender distribution of dogs with chronic hepatitis in the United Kingdom

AbstractStandardised histological criteria are now available for the diagnosis of canine chronic hepatitis (CH). CH is common in dogs, but no studies have reported breed, age and gender distributions in the United Kingdom (UK). The objective of this study was to determine which breeds had an increased risk for developing CH in the UK and to report the age and gender distribution for those breeds. The databases of six veterinary histopathology laboratories were searched for cases with a histological diagnosis of CH according to standardised criteria. The breed, age and gender of dogs was recorded and compared to a control population to calculate the odds ratio and 95% confidence intervals for developing CH.A total of 551 cases of CH were identified, consisting of 61 breeds. Nineteen breeds were represented by five or more cases. Breeds with an increased risk for developing CH included the American cocker spaniel, Cairn terrier, Dalmatian, Dobermann pinscher, English cocker spaniel, English springer spaniel, Great Dane, Labrador retriever and Samoyed. The median age at diagnosis for all breeds with CH was 8years (range 7months to 16years). Dalmatians, Dobermann pinschers and English springer spaniels with CH were significantly younger than Cairn terriers, English cocker spaniels and Labrador retrievers with CH. Females were over-represented when all cases were examined together. In conclusion, several breeds in the UK have an increased risk of CH, some of which have not been previously reported

Logarithmic and complex constant term identities

In recent work on the representation theory of vertex algebras related to the Virasoro minimal models M(2,p), Adamovic and Milas discovered logarithmic analogues of (special cases of) the famous Dyson and Morris constant term identities. In this paper we show how the identities of Adamovic and Milas arise naturally by differentiating as-yet-conjectural complex analogues of the constant term identities of Dyson and Morris. We also discuss the existence of complex and logarithmic constant term identities for arbitrary root systems, and in particular prove complex and logarithmic constant term identities for the root system G_2.Comment: 26 page