Viscous Topical Is More Effective Than Nebulized Steroid Therapy for Patients With Eosinophilic Esophagitis

We performed a randomized trial to compare nebulized and viscous topical steroid treatments for eosinophilic esophagitis (EoE). Subjects with incident EoE (n=25) received budesonide 1 mg twice daily—either nebulized and then swallowed (NEB) or as an oral viscous slurry (OVB)—for 8 weeks. Baseline eosinophil counts for the NEB and OVB groups were 101 and 83 (P=.62). Post-treatment counts were 89 and 11 (P=.02). The mucosal medication contact time, measured by scintigraphy, was higher for the OVB group than the NEB group (PP=.001). OVB was more effective than NEB in reducing numbers of esophageal eosinophils in patients with EoE. OVB provided a significantly higher level of esophageal exposure to the therapeutic agent, which correlated with lower eosinophil counts

β2-Adrenergic receptor promoter haplotype influences the severity of acute viral respiratory tract infection during infancy: a prospective cohort study

Abstract Background Despite the significant interest in β2-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. Methods To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. Results There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95 % confidence interval: 0.36, 0.98). There was no similar protective relationship of haplotype CCA on severity of respiratory tract infections identified in Caucasians. Conclusions ADRB2 genotype may be predictive of severity of acute respiratory tract infections in African Americans, and potentially identify a subset of infants who may respond to beta-agonist therapy

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Animal-borne telemetry: An integral component of the ocean observing toolkit

Animal telemetry is a powerful tool for observing marine animals and the physical environments that they inhabit, from coastal and continental shelf ecosystems to polar seas and open oceans. Satellite-linked biologgers and networks of acoustic receivers allow animals to be reliably monitored over scales of tens of meters to thousands of kilometers, giving insight into their habitat use, home range size, the phenology of migratory patterns and the biotic and abiotic factors that drive their distributions. Furthermore, physical environmental variables can be collected using animals as autonomous sampling platforms, increasing spatial and temporal coverage of global oceanographic observation systems. The use of animal telemetry, therefore, has the capacity to provide measures from a suite of essential ocean variables (EOVs) for improved monitoring of Earth's oceans. Here we outline the design features of animal telemetry systems, describe current applications and their benefits and challenges, and discuss future directions. We describe new analytical techniques that improve our ability to not only quantify animal movements but to also provide a powerful framework for comparative studies across taxa. We discuss the application of animal telemetry and its capacity to collect biotic and abiotic data, how the data collected can be incorporated into ocean observing systems, and the role these data can play in improved ocean management

A Maize Thiamine Auxotroph Is Defective in Shoot Meristem Maintenance[C][W][OA]

Mutations in the maize thiamine biosynthesis gene bladekiller1 induce meristem abortion phenotypes that are completely rescued by exogenous thiamine. The data illustrate the essential role of metabolic cofactors during the proliferative growth of the undifferentiated stem cell populations that comprise plant meristems

Intersectional global citizenship: gendered and racialized renderings

This article intervenes in the emerging field of global citizenship studies by following in the footsteps of critical studies of national citizenship, which have shown that the seemingly neutral features of citizenship are gendered and racialized. The notion of “global citizenship” has gained currency in recent years and while there is not yet a canonized account of global citizenship, it is possible to identify the main shared features of different global citizenship accounts. While the “global” of global citizenship could denote the universality of the concept in contrast to national citizenship, this promise of inclusivity is not fulfilled. This article provides an intersectional reading of global citizenship theories and examples. Dominant global citizenship accounts, I argue, contain exclusionary and marginalizing tendencies and are biased toward a certain type of global subject whose responsibility is based on benevolence. A more inclusive and radical account of global citizenship can be built by drawing on Iris Marion Young’s social connection model to rethink responsibility and by more firmly grounding it in an understanding of globalization as linked to historical and present structural inequalities