327 research outputs found
Diagnostic plasma miRNA-profiles for ovarian cancer in patients with pelvic mass
BackgroundOvarian cancer is the fifth most common cancer in women worldwide. Moreover, there are no reliable minimal invasive tests to secure the diagnosis of malignant pelvic masses. Cell-free, circulating microRNAs have the potential as diagnostic biomarkers in cancer. Here, we performed and validated a miRNA panel with the potential to distinguish OC from benign pelvic masses.MethodsThe profile of plasma microRNA was determined with a panel of 46 candidates in a discovery group and a validation group, each consisting of 190 pre-surgery plasma samples from age-matched patients with malignant (n = 95) and benign pelvic mass (n = 95), by real time RT-qPCR.ResultsFour up-regulated (miR-200c-3p, miR-221-3p, miR-21-5p, and miR-484) and two down-regulated (miR-195-5p and miR-451a) microRNAs were discovered. From those, miR-200c-3p and miR-221-3p were further confirmed in a validation cohort. A combination of these 2 microRNAs together with CA-125 yielded an overall diagnostic accuracy of AUC = 0.96.ConclusionsWe showed consistent plasma microRNA profiles that provide independent diagnostic information of late stage OC
Topological Graph Polynomials in Colored Group Field Theory
In this paper we analyze the open Feynman graphs of the Colored Group Field
Theory introduced in [arXiv:0907.2582]. We define the boundary graph
\cG_{\partial} of an open graph \cG and prove it is a cellular complex.
Using this structure we generalize the topological (Bollobas-Riordan) Tutte
polynomials associated to (ribbon) graphs to topological polynomials adapted to
Colored Group Field Theory graphs in arbitrary dimension
Low Complexity Regularization of Linear Inverse Problems
Inverse problems and regularization theory is a central theme in contemporary
signal processing, where the goal is to reconstruct an unknown signal from
partial indirect, and possibly noisy, measurements of it. A now standard method
for recovering the unknown signal is to solve a convex optimization problem
that enforces some prior knowledge about its structure. This has proved
efficient in many problems routinely encountered in imaging sciences,
statistics and machine learning. This chapter delivers a review of recent
advances in the field where the regularization prior promotes solutions
conforming to some notion of simplicity/low-complexity. These priors encompass
as popular examples sparsity and group sparsity (to capture the compressibility
of natural signals and images), total variation and analysis sparsity (to
promote piecewise regularity), and low-rank (as natural extension of sparsity
to matrix-valued data). Our aim is to provide a unified treatment of all these
regularizations under a single umbrella, namely the theory of partial
smoothness. This framework is very general and accommodates all low-complexity
regularizers just mentioned, as well as many others. Partial smoothness turns
out to be the canonical way to encode low-dimensional models that can be linear
spaces or more general smooth manifolds. This review is intended to serve as a
one stop shop toward the understanding of the theoretical properties of the
so-regularized solutions. It covers a large spectrum including: (i) recovery
guarantees and stability to noise, both in terms of -stability and
model (manifold) identification; (ii) sensitivity analysis to perturbations of
the parameters involved (in particular the observations), with applications to
unbiased risk estimation ; (iii) convergence properties of the forward-backward
proximal splitting scheme, that is particularly well suited to solve the
corresponding large-scale regularized optimization problem
Developing a predictive modelling capacity for a climate change-vulnerable blanket bog habitat: Assessing 1961-1990 baseline relationships
Aim: Understanding the spatial distribution of high priority habitats and
developing predictive models using climate and environmental variables to
replicate these distributions are desirable conservation goals. The aim of this
study was to model and elucidate the contributions of climate and topography to
the distribution of a priority blanket bog habitat in Ireland, and to examine how
this might inform the development of a climate change predictive capacity for
peat-lands in Ireland.
Methods: Ten climatic and two topographic variables were recorded for grid
cells with a spatial resolution of 1010 km, covering 87% of the mainland
land surface of Ireland. Presence-absence data were matched to these variables
and generalised linear models (GLMs) fitted to identify the main climatic and
terrain predictor variables for occurrence of the habitat. Candidate predictor
variables were screened for collinearity, and the accuracy of the final fitted GLM
was evaluated using fourfold cross-validation based on the area under the curve
(AUC) derived from a receiver operating characteristic (ROC) plot. The GLM
predicted habitat occurrence probability maps were mapped against the actual
distributions using GIS techniques.
Results: Despite the apparent parsimony of the initial GLM using only climatic
variables, further testing indicated collinearity among temperature and precipitation
variables for example. Subsequent elimination of the collinear variables and
inclusion of elevation data produced an excellent performance based on the AUC
scores of the final GLM. Mean annual temperature and total mean annual
precipitation in combination with elevation range were the most powerful
explanatory variable group among those explored for the presence of blanket
bog habitat.
Main conclusions: The results confirm that this habitat distribution in general
can be modelled well using the non-collinear climatic and terrain variables tested
at the grid resolution used. Mapping the GLM-predicted distribution to the
observed distribution produced useful results in replicating the projected
occurrence of the habitat distribution over an extensive area. The methods
developed will usefully inform future climate change predictive modelling for
Irelan
Directed Flow in 158 A GeV + Collisions
The directed flow of protons and positive pions have been studied in 158 A GeV Pb + Pb collisions. A directed flow analysis of the rapidity dependence of the average transverse momentum projected onto the reaction plane is presented for semi-central collisions with impact parameters of approximately 8 fm, where the flow effect is largest. The magnitude of the directed flow is found to be significantly smaller than observed at AGS energies and than RQMD model predictions.The directed flow of protons and positive pions have been studied in 158 A GeV Pb + Pb collisions. A directed flow analysis of the rapidity dependence of the average transverse momentum projected onto the reaction plane is presented for semi-central collisions with impact parameters of approximately 8 fm, where the flow effect is largest. The magnitude of the directed flow is found to be significantly smaller than observed at AGS energies and than RQMD model predictions
Novel genetic loci associated with hippocampal volume
The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness
Bio-analytical Assay Methods used in Therapeutic Drug Monitoring of Antiretroviral Drugs-A Review
Analysis of shared heritability in common disorders of the brain
ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders
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