Managing clinically significant findings in research:the UK10K example

Recent advances in sequencing technology allow data on the human genome to be generated more quickly and in greater detail than ever before. Such detail includes findings that may be of significance to the health of the research participant involved. Although research studies generally do not feed back information on clinically significant findings (CSFs) to participants, this stance is increasingly being questioned. There may be difficulties and risks in feeding clinically significant information back to research participants, however, the UK10K consortium sought to address these by creating a detailed management pathway. This was not intended to create any obligation upon the researchers to feed back any CSFs they discovered. Instead, it provides a mechanism to ensure that any such findings can be passed on to the participant where appropriate. This paper describes this mechanism and the specific criteria, which must be fulfilled in order for a finding and participant to qualify for feedback. This mechanism could be used by future research consortia, and may also assist in the development of sound principles for dealing with CSFs

A Continental-Wide Perspective: The Genepool of Nuclear Encoded Ribosomal DNA and Single-Copy Gene Sequences in North American Boechera (Brassicaceae)

74 of the currently accepted 111 taxa of the North American genus Boechera (Brassicaceae) were subject to pyhlogenetic reconstruction and network analysis. The dataset comprised 911 accessions for which ITS sequences were analyzed. Phylogenetic analyses yielded largely unresolved trees. Together with the network analysis confirming this result this can be interpreted as an indication for multiple, independent, and rapid diversification events. Network analyses were superimposed with datasets describing i) geographical distribution, ii) taxonomy, iii) reproductive mode, and iv) distribution history based on phylogeographic evidence. Our results provide first direct evidence for enormous reticulate evolution in the entire genus and give further insights into the evolutionary history of this complex genus on a continental scale. In addition two novel single-copy gene markers, orthologues of the Arabidopsis thaliana genes At2g25920 and At3g18900, were analyzed for subsets of taxa and confirmed the findings obtained through the ITS data

Institutional shared resources and translational cancer research

The development and maintenance of adequate shared infrastructures is considered a major goal for academic centers promoting translational research programs. Among infrastructures favoring translational research, centralized facilities characterized by shared, multidisciplinary use of expensive laboratory instrumentation, or by complex computer hardware and software and/or by high professional skills are necessary to maintain or improve institutional scientific competitiveness. The success or failure of a shared resource program also depends on the choice of appropriate institutional policies and requires an effective institutional governance regarding decisions on staffing, existence and composition of advisory committees, policies and of defined mechanisms of reporting, budgeting and financial support of each resource. Shared Resources represent a widely diffused model to sustain cancer research; in fact, web sites from an impressive number of research Institutes and Universities in the U.S. contain pages dedicated to the SR that have been established in each Center, making a complete view of the situation impossible. However, a nation-wide overview of how Cancer Centers develop SR programs is available on the web site for NCI-designated Cancer Centers in the U.S., while in Europe, information is available for individual Cancer centers. This article will briefly summarize the institutional policies, the organizational needs, the characteristics, scientific aims, and future developments of SRs necessary to develop effective translational research programs in oncology

Developmental malformation of the corpus callosum: a review of typical callosal development and examples of developmental disorders with callosal involvement

This review provides an overview of the involvement of the corpus callosum (CC) in a variety of developmental disorders that are currently defined exclusively by genetics, developmental insult, and/or behavior. I begin with a general review of CC development, connectivity, and function, followed by discussion of the research methods typically utilized to study the callosum. The bulk of the review concentrates on specific developmental disorders, beginning with agenesis of the corpus callosum (AgCC)—the only condition diagnosed exclusively by callosal anatomy. This is followed by a review of several genetic disorders that commonly result in social impairments and/or psychopathology similar to AgCC (neurofibromatosis-1, Turner syndrome, 22q11.2 deletion syndrome, Williams yndrome, and fragile X) and two forms of prenatal injury (premature birth, fetal alcohol syndrome) known to impact callosal development. Finally, I examine callosal involvement in several common developmental disorders defined exclusively by behavioral patterns (developmental language delay, dyslexia, attention-deficit hyperactive disorder, autism spectrum disorders, and Tourette syndrome)

ISSN exercise & sport nutrition review: research & recommendations

Sports nutrition is a constantly evolving field with hundreds of research papers published annually. For this reason, keeping up to date with the literature is often difficult. This paper is a five year update of the sports nutrition review article published as the lead paper to launch the JISSN in 2004 and presents a well-referenced overview of the current state of the science related to how to optimize training and athletic performance through nutrition. More specifically, this paper provides an overview of: 1.) The definitional category of ergogenic aids and dietary supplements; 2.) How dietary supplements are legally regulated; 3.) How to evaluate the scientific merit of nutritional supplements; 4.) General nutritional strategies to optimize performance and enhance recovery; and, 5.) An overview of our current understanding of the ergogenic value of nutrition and dietary supplementation in regards to weight gain, weight loss, and performance enhancement. Our hope is that ISSN members and individuals interested in sports nutrition find this review useful in their daily practice and consultation with their clients

Species-based comparison of disease severity and risk factors for disseminated Candida infections in pediatric patients

John J Hawkshead III,1 Russell B Van Dyke,2 Susan E Hassig,3 Larry S Webber,4 Rodolfo E Begue5 1Merck & Co, CORE Hospital Specialty Group, Rahway, NJ, 2Department of Pediatrics, Tulane University School of Medicine, 3Department of Epidemiology, 4Department of Biostatistics, Tulane University School of Public Health and Tropical Medicine, 5Department of Pediatrics, Louisiana State University Health Sciences Center, New Orleans, LA, USA Background: Pediatric Candida infections are associated with worse clinical outcomes and increased costs. Yet, it is not definitively known if particular species are associated with more severe illness. Differential risk factor exposures among the species group may also exist. We aimed to determine whether certain Candida species are more strongly associated with worse outcomes, and whether certain risk factors more strongly predispose patients to infection with certain species. Methods: Microbiology lab records from patients seen from 2003 to 2010 at an urban children's hospital were reviewed for invasive or disseminated Candida infections. Data on measures of disease severity/outcome and risk factors were abstracted and analyzed to determine differences associated with various Candida species. Results: Exactly 106 cases of infection were analyzed. Non-albicans species were associated with a significantly longer length of stay postdiagnosis (P=0.03), as well as longer treatment (P=0.02). Candida albicans was associated with a higher number of antihypotensive medications required (P=0.03) and length of mechanical ventilation postdiagnosis (P=0.05). Candida tropicalis was associated with the highest mortality (45.5%). Hypotension, which was found to be significantly associated with concurrent infection, was significantly associated with increased risk of mortality (odds ratio =5.85, P=0.005). Initial choice of antifungal therapy was not associated with differences in eventual patient mortality. Multivariate logistic regression modeling revealed a trend toward C. albicans infection in patients receiving antineoplastic chemotherapy and non-albicans infection in patients with >96 hours mechanical ventilation. Conclusion: Interspecies differences may exist for Candida in terms of disease severity and risk factors. Underlying morbidity and the role of concurrent infections may play a key role in poor outcomes. Keywords: Candida, disseminated, pediatric, severity, risk factors, fungemia, antifungal, coinfectio