Massively Parallel RNA Sequencing Identifies a Complex Immune Gene Repertoire in the lophotrochozoan Mytilus edulis

The marine mussel Mytilus edulis and its closely related sister species are distributed world-wide and play an important role in coastal ecology and economy. The diversification in different species and their hybrids, broad ecological distribution, as well as the filter feeding mode of life has made this genus an attractive model to investigate physiological and molecular adaptations and responses to various biotic and abiotic environmental factors. In the present study we investigated the immune system of Mytilus, which may contribute to the ecological plasticity of this species. We generated a large Mytilus transcriptome database from different tissues of immune challenged and stress treated individuals from the Baltic Sea using 454 pyrosequencing. Phylogenetic comparison of orthologous groups of 23 species demonstrated the basal position of lophotrochozoans within protostomes. The investigation of immune related transcripts revealed a complex repertoire of innate recognition receptors and downstream pathway members including transcripts for 27 toll-like receptors and 524 C1q domain containing transcripts. NOD-like receptors on the other hand were absent. We also found evidence for sophisticated TNF, autophagy and apoptosis systems as well as for cytokines. Gill tissue and hemocytes showed highest expression of putative immune related contigs and are promising tissues for further functional studies. Our results partly contrast with findings of a less complex immune repertoire in ecdysozoan and other lophotrochozoan protostomes. We show that bivalves are interesting candidates to investigate the evolution of the immune system from basal metazoans to deuterostomes and protostomes and provide a basis for future molecular work directed to immune system functioning in Mytilus

A multi-source feedback tool for measuring a subset of Pediatrics Milestones

Background: The Pediatrics Milestones Assessment Pilot employed a new multisource feedback (MSF) instrument to assess nine Pediatrics Milestones among interns and subinterns in the inpatient context. Objective: To report validity evidence for the MSF tool for informing milestone classification decisions. Methods: We obtained MSF instruments by different raters per learner per rotation. We present evidence for validity based on the unified validity framework. Results: One hundred and ninety two interns and 41 subinterns at 18 Pediatrics residency programs received a total of 1084 MSF forms from faculty (40%), senior residents (34%), nurses (22%), and other staff (4%). Variance in ratings was associated primarily with rater (32%) and learner (22%). The milestone factor structure fit data better than simpler structures. In domains except professionalism, ratings by nurses were significantly lower than those by faculty and ratings by other staff were significantly higher. Ratings were higher when the rater observed the learner for longer periods and had a positive global opinion of the learner. Ratings of interns and subinterns did not differ, except for ratings by senior residents. MSF-based scales correlated with summative milestone scores. Conclusion: We obtain moderately reliable MSF ratings of interns and subinterns in the inpatient context to inform some milestone assignments

Longitudinal study of implantable cardioverter-defibrillators: methods and clinical characteristics of patients receiving implantable cardioverter-defibrillators for primary prevention in contemporary practice

Background- Implantable cardioverter-defibrillators (ICDs) are increasingly used for primary prevention after randomized, controlled trials demonstrating that they reduce the risk of death in patients with left ventricular systolic dysfunction. The extent to which the clinical characteristics and long-term outcomes of unselected, community-based patients with left ventricular systolic dysfunction undergoing primary prevention ICD implantation in a real-world setting compare with those enrolled in the randomized, controlled trials is not well characterized. This study is being conducted to address these questions. Methods and Results- The study cohort includes consecutive patients undergoing primary prevention ICD placement between January 1, 2006 and December 31, 2009 in 7 health plans. Baseline clinical characteristics were acquired from the National Cardiovascular Data Registry ICD Registry. Longitudinal data collection is underway, and will include hospitalization, mortality, and resource use from standardized health plan data archives. Data regarding ICD therapies will be obtained through chart abstraction and adjudicated by a panel of experts in device therapy. Compared with the populations of primary prevention ICD therapy randomized, controlled trials, the cohort (n=2621) is on average significantly older (by 2.5-6.5 years), more often female, more often from racial and ethnic minority groups, and has a higher burden of coexisting conditions. The cohort is similar, however, to a national population undergoing primary prevention ICD placement. Conclusions- Patients undergoing primary prevention ICD implantation in this study differ from those enrolled in the randomized, controlled trials that established the efficacy of ICDs. Understanding a broad range of health outcomes, including ICD therapies, will provide patients, clinicians, and policy makers with contemporary data to inform decision-making