An FDA bioinformatics tool for microbial genomics research on molecular characterization of bacterial foodborne pathogens using microarrays

<p>Abstract</p> <p>Background</p> <p>Advances in microbial genomics and bioinformatics are offering greater insights into the emergence and spread of foodborne pathogens in outbreak scenarios. The Food and Drug Administration (FDA) has developed a genomics tool, ArrayTrack^TM, which provides extensive functionalities to manage, analyze, and interpret genomic data for mammalian species. ArrayTrack^TM has been widely adopted by the research community and used for pharmacogenomics data review in the FDA’s Voluntary Genomics Data Submission program. </p> <p>Results</p> <p>ArrayTrack^TM has been extended to manage and analyze genomics data from bacterial pathogens of human, animal, and food origin. It was populated with bioinformatics data from public databases such as NCBI, Swiss-Prot, KEGG Pathway, and Gene Ontology to facilitate pathogen detection and characterization. ArrayTrack^TM’s data processing and visualization tools were enhanced with analysis capabilities designed specifically for microbial genomics including flag-based hierarchical clustering analysis (HCA), flag concordance heat maps, and mixed scatter plots. These specific functionalities were evaluated on data generated from a custom Affymetrix array (FDA-ECSG) previously developed within the FDA. The FDA-ECSG array represents 32 complete genomes of <it>Escherichia coli</it> and<it> Shigella.</it> The new functions were also used to analyze microarray data focusing on antimicrobial resistance genes from <it>Salmonella</it> isolates in a poultry production environment using a universal antimicrobial resistance microarray developed by the United States Department of Agriculture (USDA).</p> <p>Conclusion</p> <p>The application of ArrayTrack^TM to different microarray platforms demonstrates its utility in microbial genomics research, and thus will improve the capabilities of the FDA to rapidly identify foodborne bacteria and their genetic traits (e.g., antimicrobial resistance, virulence, etc.) during outbreak investigations. ArrayTrack^TM is free to use and available to public, private, and academic researchers at <url>http://www.fda.gov/ArrayTrack</url>. </p

Age of Child, More than HPV Type, Is Associated with Clinical Course in Recurrent Respiratory Papillomatosis

Background: RRP is a devastating disease in which papillomas in the airway cause hoarseness and breathing difficulty. The disease is caused by human papillomavirus (HPV), 6 or 11 and is very variable. Patients undergo multiple surgeries to maintain a patent airway and in order to communicate vocally. Several small studies have been published in which most have noted that HPV 11 is associated with a more aggressive course. Methodology/Principal Findings: Papilloma biopsies were taken from patients undergoing surgical treatment of RRP and were subjected to HPV typing. 118 patients with juvenile-onset RRP with a least 1 year of clinical data and infected with a single HPV type were analyzed. HPV 11 was encountered in 40% of the patients. By our definition, most of the patients in the sample (81%) had run an aggressive course. The odds of a patient with HPV 11 running an aggressive course were 3.9 times higher that that of patients with HPV 6 (Fisher's exact p=0.017). However, clinical course was more closely associated with age of the patient (at diagnosis and at the time of the current surgery) than with HPV type. Patients with HPV 11 were diagnosed at a younger age (2.4y) than were those with HPV 6 (3.4y) (p=0.014). Both by multiple linear regression and by multiple logistics regression HPV type was only weakly associated with metrics of disease course when simultaneously accounting for age. Conclusions/Significance Abstract: The course of RRP is variable and a quarter of the variability can be accounted for by the age of the patient. HPV 11 is more closely associated with a younger age at diagnosis than it is associated with an aggressive clinical course. These data suggest that there are factors other than HPV type and age of the patient that determine disease course. © 2008 Buchinsky et al

Smoke with Fire: Financial Crises and the Demand for Parliamentary Oversight in the European Union.

The handling of the 2008 financial crisis has reinforced the conviction that the European Union (EU) is undemocratic and that member states are forced to delegate overwhelming power to a supranational technocracy. However, European countries have engaged with this alleged power drift differently, with only a few member states demanding more parliamentary scrutiny of EU institutions. This article develops a political economy explanation for why only some states have enforced mechanisms to monitor the EU more closely. Our theory focuses on the role of the crisis and the impact of fiscal autonomy in countries outside and inside currency arrangements such as the European Economic and Monetary Union (EMU). We argue that, in the aftermath of a severe economic shock, member states outside the EMU possess more monetary and fiscal resources to handle the crisis. These would then demand oversight of EU decision-making if their fiscal sustainability depends on the Union. By contrast, Eurozone states that need policy changes cannot address the crisis independently or initiate reforms to scrutinize the EU. Hence, we argue that during the heated moments of severe economic downturns, parliaments in Eurozone countries discuss supranational supervision rarely. As these legislatures have nevertheless to give in to the popular demand for EU control, they express support for more EU supervision in the infrequent times of debate. We provide evidence for our theory with a cross-national analysis of EU oversight institutions, and a new original dataset of parliamentary debates during the Eurozone crisis. Our findings highlight the political consequences that financial nosedives have across the diverse membership of a supranational organization

Towards a probabilistic regional reanalysis system for Europe: evaluation of precipitation from experiments

A new development in the field of reanalyses is the incorporation of uncertainty estimation capabilities. We have developed a probabilistic regional reanalysis system for the CORDEX-EUR11 domain that is based on the numerical weather prediction model COSMO at a 12-km grid spacing. The lateral boundary conditions of all ensemble members are provided by the global reanalysis ERA-Interim. In the basic implementation of the system, uncertainties due to observation errors are estimated. Atmospheric assimilation of conventional observations perturbed by means of random samples of observation error yields estimates of the reanalysis uncertainty conditioned to observation errors. The data assimilation employed is a new scheme based on observation nudging that we denote ensemble nudging. The lower boundary of the atmosphere is regularly updated by external snow depth, sea surface temperature and soil moisture analyses. One of the most important purposes of reanalyses is the estimation of so-called essential climate variables. For regional reanalyses, precipitation has been identified as one of the essential climate variables that are potentially better represented than in other climate data sets. For that reason, we assess the representation of precipitation in our system in a pilot study. Based on two experiments, each of which extends over one month, we conduct a preliminary comparison to the global reanalysis ERA-Interim, a dynamical downscaling of the latter and the high-resolution regional reanalysis COSMO-REA6. In a next step, we assess our reanalysis system's probabilistic capabilities versus the ECMWF-EPS in terms of six-hourly precipitation sums. The added value of our probabilistic regional reanalysis system motivates the current production of a 5-year-long test reanalysis COSMO-EN-REA12 in the framework of the FP7-funded project Uncertainties in Ensembles of Regional Re-Analyses (UERRA)