A hierarchical Bayesian model for inference of copy number variants and their association to gene expression

A number of statistical models have been successfully developed for the analysis of high-throughput data from a single source, but few methods are available for integrating data from different sources. Here we focus on integrating gene expression levels with comparative genomic hybridization (CGH) array measurements collected on the same subjects. We specify a measurement error model that relates the gene expression levels to latent copy number states which, in turn, are related to the observed surrogate CGH measurements via a hidden Markov model. We employ selection priors that exploit the dependencies across adjacent copy number states and investigate MCMC stochastic search techniques for posterior inference. Our approach results in a unified modeling framework for simultaneously inferring copy number variants (CNV) and identifying their significant associations with mRNA transcripts abundance. We show performance on simulated data and illustrate an application to data from a genomic study on human cancer cell lines.Comment: Published in at http://dx.doi.org/10.1214/13-AOAS705 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Convergence in measure under Finite Additivity

We investigate the possibility of replacing the topology of convergence in probability with convergence in $L^1$. A characterization of continuous linear functionals on the space of measurable functions is also obtained

New development: Directly elected mayors in Italy: creating a strong leader doesn’t mean creating strong leadership

More than 20 years after their introduction, directly elected mayors are key players in Italian urban governance. This article explains the main effects of this reform on local government systems and provides lessons for other countries considering directly elected mayors

Post-operative morbidity following pancreatic duct occlusion without anastomosis after pancreaticoduodenectomy: a systematic review and meta-analysis

Background: Pancreatic duct occlusion (PDO) without anastomosis is a technique proposed to mitigate the clinical consequences of postoperative pancreatic fistulas (POPF) after pancreaticoduodenectomy. The aim of this study was to appraise the morbidity following PDO through a systematic review and meta-analysis. Methods: A systematic search of MEDLINE, Embase, and Web Of Science identified studies reporting outcomes of PDO following pancreaticoduodenectomy. Pooled prevalence rates of postoperative complications and mortality were computed using random-effect modeling. Meta-regression analyses were performed to examine the impact of moderators on the overall estimates. Results: Sixteen studies involving 1000 patients were included. Pooled postoperative mortality was 2.7%. A POPF was reported in 29.7% of the patients. Clinically relevant POPFs occurred in 13.5% of the patients, while intra-abdominal abscess and haemorrhages occurred in 6.7% and 5.5% of the patients, respectively. Re-operation was necessary in 7.6% of the patients. Postoperatively new onset diabetes occurred in 15.8% of patients, more frequently after the use of chemical substances for PDO (p = 0.003). Conclusions: PDO is associated with significant morbidity including new onset of post-operative diabetes. The risk of new onset post-operative diabetes is associated with the use of chemical substance for PDO. Further evidence is needed to evaluate the potential benefits of PDO in patients at high risk of POPF

The practices of apartheid as a war crime: a critical analysis

The human suffering caused by the political ideology of apartheid in South Africa during the Apartheid era (1948-1994) prompted worldwide condemnation and a variety of diplomatic and legal responses. Amongst these responses was the attempt to have apartheid recognised both as a crime against humanity in the 1973 Apartheid Convention as well as a war crime in Article 85(4)(c) of Additional Protocol I. This article examines the origins, nature and current status of the practices of apartheid as a war crime and its possible application to the Israeli-Palestinian conflict

Portal venous gas after a failed endoscopic retrograde cholangiopancreatography attempt in a patient with a large hepatocellular carcinoma: A case report

The cause of hepatic portal vein gas (HPVG) is variable. Good knowledge of the possible causes, combined with the clinical assessment of the patient and a good quality imaging, is required to correctly identify the underlying cause of HPVG and to best predict the prognosis

Robust pricing and hedging of double no-touch options

Double no-touch options, contracts which pay out a fixed amount provided an underlying asset remains within a given interval, are commonly traded, particularly in FX markets. In this work, we establish model-free bounds on the price of these options based on the prices of more liquidly traded options (call and digital call options). Key steps are the construction of super- and sub-hedging strategies to establish the bounds, and the use of Skorokhod embedding techniques to show the bounds are the best possible. In addition to establishing rigorous bounds, we consider carefully what is meant by arbitrage in settings where there is no {\it a priori} known probability measure. We discuss two natural extensions of the notion of arbitrage, weak arbitrage and weak free lunch with vanishing risk, which are needed to establish equivalence between the lack of arbitrage and the existence of a market model.Comment: 32 pages, 5 figure

Complex effective index in graphene-silicon waveguides

We report for the first time and characterize experimentally the complex optical conductivity of graphene on silicon photonic waveguides. This permits us to predict accurately the behavior of photonic integrated devices encompassing graphene layers. Exploiting a Si microring add/drop resonator, we show the effect of electrical gating of graphene on the complex effective index of the waveguide by measuring both the wavelength shift of the resonance and the change in the drop peak transmission. Due to electro-refractive effect of graphene a giant (>10 123) change in the effective index is demonstrated for the first time on Si photonics waveguides and this large effect will crucially impact performances and consumption of Si photonics devices. We confirmed the results by two independent experiments involving two different gating schemes: Si gating through the ridge waveguide, and polymer-electrolyte gating. Both the experiments demonstrate a very large phase effect in good agreement with numerical calculations. The reported results validate the Kubo model for the case of graphene-Si photonics interfaces and for propagation in this type of waveguide. This is fundamental for the next design and fabrication of future graphene-silicon photonics devices

Regulatory noncoding and predicted pathogenic coding variants of ccr5 predispose to severe covid-19

Genome-wide association studies (GWAS) found locus 3p21.31 associated with severe COVID-19. CCR5 resides at the same locus and, given its known biological role in other infection diseases, we investigated if common noncoding and rare coding variants, affecting CCR5, can predispose to severe COVID-19. We combined single nucleotide polymorphisms (SNPs) that met the suggestive significance level (P ≤ 1 × 10−5 ) at the 3p21.31 locus in public GWAS datasets (6406 COVID-19 hospitalized patients and 902,088 controls) with gene expression data from 208 lung tissues, Hi-C, and Chip-seq data. Through whole exome sequencing (WES), we explored rare coding variants in 147 severe COVID-19 patients. We identified three SNPs (rs9845542, rs12639314, and rs35951367) associated with severe COVID-19 whose risk alleles correlated with low CCR5 expression in lung tissues. The rs35951367 resided in a CTFC binding site that interacts with CCR5 gene in lung tissues and was confirmed to be associated with severe COVID-19 in two independent datasets. We also identified a rare coding variant (rs34418657) associated with the risk of developing severe COVID-19. Our results suggest a biological role of CCR5 in the progression of COVID-19 as common and rare genetic variants can increase the risk of developing severe COVID-19 by affecting the functions of CCR5