47 research outputs found
An eQTL Landscape of Kidney Tissue in Human Nephrotic Syndrome
© 2018 American Society of Human Genetics Expression quantitative trait loci (eQTL) studies illuminate the genetics of gene expression and, in disease research, can be particularly illuminating when using the tissues directly impacted by the condition. In nephrology, there is a paucity of eQTL studies of human kidney. Here, we used whole-genome sequencing (WGS) and microdissected glomerular (GLOM) and tubulointerstitial (TI) transcriptomes from 187 individuals with nephrotic syndrome (NS) to describe the eQTL landscape in these functionally distinct kidney structures. Using MatrixEQTL, we performed cis-eQTL analysis on GLOM (n = 136) and TI (n = 166). We used the Bayesian âDeterministic Approximation of Posteriorsâ (DAP) to fine-map these signals, eQTLBMA to discover GLOM- or TI-specific eQTLs, and single-cell RNA-seq data of control kidney tissue to identify the cell type specificity of significant eQTLs. We integrated eQTL data with an IgA Nephropathy (IgAN) GWAS to perform a transcriptome-wide association study (TWAS). We discovered 894 GLOM eQTLs and 1,767 TI eQTLs at FDR \u3c 0.05. 14% and 19% of GLOM and TI eQTLs, respectively, had \u3e1 independent signal associated with its expression. 12% and 26% of eQTLs were GLOM specific and TI specific, respectively. GLOM eQTLs were most significantly enriched in podocyte transcripts and TI eQTLs in proximal tubules. The IgAN TWAS identified significant GLOM and TI genes, primarily at the HLA region. In this study, we discovered GLOM and TI eQTLs, identified those that were tissue specific, deconvoluted them into cell-specific signals, and used them to characterize known GWAS alleles. These data are available for browsing and download via our eQTL browser, ânephQTL.
Reference Distorted Prices
I show that when consumers (mis)perceive prices relative to reference prices,
budgets turn out to be soft, prices tend to be lower and the average quality of
goods sold decreases. These observations provide explanations for decentralized
purchase decisions, for people being happy with a purchase even when they have
paid their evaluation, and for why trade might affect high quality local firms
'unfairly'
The willingness-to-accept/willingness-to-pay disparity in repeated markets : loss aversion or 'bad-deal' aversion?
Several experimental studies have reported that an otherwise robust regularity-the disparity between Willingness-To-Accept and Willingness-To-Pay-tends to be greatly reduced in repeated markets, posing a serious challenge to existing reference-dependent and reference-independent models alike. This article offers a new account of the evidence, based on the assumptions that individuals are affected by good and bad deals relative to the expected transaction price (price sensitivity), with bad deals having a larger impact on their utility ('bad-deal' aversion). These features of preferences explain the existing evidence better than alternative approaches, including the most recent developments of loss aversion models
Is Having More Channels Really Better? A Model of Competition Among Commercial Television Broadcasters
Determining farm effects attributable to the introduction and use of a dairy management information system in The Netherlands
Estimating Discrete Joint Probability Distributions for Demographic Characteristics at the Store Level Given Store Level Marginal Distributions and a City-Wide Joint Distribution
This paper provides a solution to the problem of estimating a joint distribution using the associated marginal distributions and a related joint distribution. The particular application we have in mind is estimating joint distributions of demographic characteristics corresponding to market areas for individual retail stores. Marginal distributions are generally available at the census tract level, but joint distributions are only available for Metropolitan Statistical Areas which are generally much larger than the market for a single retail store. Joint distributions over demographics are an important input into mixed logit demand models for aggregate data. Market shares that vary systematically with demographics are essential for relieving the restrictions imposed by the Independence from Irrelevant Alternative property of the logit model. We approach this problem by formulating a parametric function that incorporates both the city-wide joint distributional information and marginal information specific to the retail storeâs market area. To estimate the function, we form moment conditions equating the moments of the parametric function to observed data, and we input these into a GMM objective. In one of our illustrations we use four marginal demographic distributions from each of eight stores in Dominickâs Finer Foods data archive to estimate a four dimensional joint distribution for each store. Our results show that our GMM approach produces estimated joint distributions that differ substantially from the product of marginal distributions and emit marginals that closely match the observed marginal distributions. Mixed logit demand estimates are also presented which show the estimates to be sensitive to the formulation of the demographics distribution. Copyright Springer Science + Business Media, Inc. 2005mixed logit, discrete joint probability distributions, generalized method of moments,
Systemic Inflammatory Mediators Are Effective Biomarkers for Predicting Adverse Outcomes in Clostridioides difficile Infection
Each year in the United States, Clostridioides difficile causes nearly 500,000 gastrointestinal infections that range from mild diarrhea to severe colitis and death. The ability to identify patients at increased risk for severe disease or mortality at the time of diagnosis of C. difficile infection (CDI) would allow clinicians to effectively allocate disease modifying therapies. In this study, we developed models consisting of only a small number of serum biomarkers that are capable of predicting both 30-day all-cause mortality and adverse outcomes of patients at time of CDI diagnosis. We were able to validate these models through experimental mouse infection. This provides evidence that the biomarkers reflect the underlying pathophysiology and that our mouse model of CDI reflects the pathogenesis of human infection. Predictive models can not only assist clinicians in identifying patients at risk for severe CDI but also be utilized for targeted enrollment in clinical trials aimed at reduction of adverse outcomes from severe CDI.Clostridioides difficile infection (CDI) can result in severe disease and death, with no accurate models that allow for early prediction of adverse outcomes. To address this need, we sought to develop serum-based biomarker models to predict CDI outcomes. We prospectively collected sera â€48 h after diagnosis of CDI in two cohorts. Biomarkers were measured with a custom multiplex bead array assay. Patients were classified using IDSA severity criteria and the development of disease-related complications (DRCs), which were defined as ICU admission, colectomy, and/or death attributed to CDI. Unadjusted and adjusted models were built using logistic and elastic net modeling. The best model for severity included procalcitonin (PCT) and hepatocyte growth factor (HGF) with an area (AUC) under the receiver operating characteristic (ROC) curve of 0.74 (95% confidence interval, 0.67 to 0.81). The best model for 30-day mortality included interleukin-8 (IL-8), PCT, CXCL-5, IP-10, and IL-2Rα with an AUC of 0.89 (0.84 to 0.95). The best model for DRCs included IL-8, procalcitonin, HGF, and IL-2Rα with an AUC of 0.84 (0.73 to 0.94). To validate our models, we employed experimental infection of mice with C. difficile. Antibiotic-treated mice were challenged with C. difficile and a similar panel of serum biomarkers was measured. Applying each model to the mouse cohort of severe and nonsevere CDI revealed AUCs of 0.59 (0.44 to 0.74), 0.96 (0.90 to 1.0), and 0.89 (0.81 to 0.97). In both human and murine CDI, models based on serum biomarkers predicted adverse CDI outcomes. Our results support the use of serum-based biomarker panels to inform Clostridioides difficile infection treatment