Ten Simple Rules for Digital Data Storage

Data is the central currency of science, but the nature of scientific data has changed dramatically with the rapid pace of technology. This change has led to the development of a wide variety of data formats, dataset sizes, data complexity, data use cases, and data sharing practices. Improvements in high throughput DNA sequencing, sustained institutional support for large sensor networks, and sky surveys with large-format digital cameras have created massive quantities of data. At the same time, the combination of increasingly diverse research teams and data aggregation in portals (e.g. for biodiversity data, GBIF or iDigBio) necessitates increased coordination among data collectors and institutions. As a consequence, “data” can now mean anything from petabytes of information stored in professionally-maintained databases, through spreadsheets on a single computer, to hand-written tables in lab notebooks on shelves. All remain important, but data curation practices must continue to keep pace with the changes brought about by new forms and practices of data collection and storage.</jats:p

Variants in the GPR146 Gene Are Associated With a Favorable Cardiometabolic Risk Profile

BACKGROUND: In mice, GPR146 (G-protein-coupled receptor 146) deficiency reduces plasma lipids and protects against atherosclerosis. Whether these findings translate to humans is unknown. METHODS: Common and rare genetic variants in the GPR146 gene locus were used as research instruments in the UK-Biobank. The Lifelines, and The Copenhagen-City Heart Study, and a cohort of individuals with familial hypobetalipoproteinemia were used to find and study rare GPR146 variants. RESULTS: In the UK-Biobank, carriers of the common rs2362529-C allele present with lower low-density lipoprotein cholesterol, apo (apolipoprotein) B, high-density lipoprotein cholesterol, apoAI, CRP (C-reactive protein), and plasma liver enzymes compared with noncarriers. Carriers of the common rs1997243-G allele, associated with higher GPR146 expression, present with the exact opposite phenotype. The associations with plasma lipids of the above alleles are allele dose-dependent. Heterozygote carriers of a rare coding variant (p.Pro62Leu; n=2615), predicted to be damaging, show a stronger reductions in the above parameters compared with carriers of the common rs2362529-C allele. The p.Pro62Leu variant is furthermore shown to segregate with low low-density lipoprotein cholesterol in a family with familial hypobetalipoproteinemia. Compared with controls, carriers of the common rs2362529-C allele show a marginally reduced risk of coronary artery disease (P=0.03) concomitant with a small effect size on low-density lipoprotein cholesterol (average decrease of 2.24 mg/dL in homozygotes) of this variant. Finally, mendelian randomization analyses suggest a causal relationship between GPR146 gene expression and plasma lipid and liver enzyme levels. CONCLUSIONS: This study shows that carriers of new genetic GPR146 variants have a beneficial cardiometabolic risk profile, but it remains to be shown whether genetic or pharmaceutical inhibition of GPR146 protects against atherosclerosis in humans

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Analysis of BAC-end sequences in rainbow trout: Content characterization and assessment of synteny between trout and other fish genomes

<p>Abstract</p> <p>Background</p> <p>Rainbow trout (<it>Oncorhynchus mykiss</it>) are cultivated worldwide for aquaculture production and are widely used as a model species to gain knowledge of many aspects of fish biology. The common ancestor of the salmonids experienced a whole genome duplication event, making extant salmonids such as the rainbow trout an excellent model for studying the evolution of tetraploidization and re-diploidization in vertebrates. However, the lack of a reference genome sequence hampers research progress for both academic and applied purposes. In order to enrich the genomic tools already available in this species and provide further insight on the complexity of its genome, we sequenced a large number of rainbow trout BAC-end sequences (BES) and characterized their contents.</p> <p>Results</p> <p>A total of 176,485 high quality BES, were generated, representing approximately 4% of the trout genome. BES analyses identified 6,848 simple sequence repeats (SSRs), of which 3,854 had high quality flanking sequences for PCR primers design. The first rainbow trout repeat elements database (INRA RT rep1.0) containing 735 putative repeat elements was developed, and identified almost 59.5% of the BES database in base-pairs as repetitive sequence. Approximately 55% of the BES reads (97,846) had more than 100 base pairs of contiguous non-repetitive sequences. The fractions of the 97,846 non-repetitive trout BES reads that had significant BLASTN hits against the zebrafish, medaka and stickleback genome databases were 15%, 16.2% and 17.9%, respectively, while the fractions of the non-repetitive BES reads that had significant BLASTX hits against the zebrafish, medaka, and stickleback protein databases were 10.7%, 9.5% and 9.5%, respectively. Comparative genomics using paired BAC-ends revealed several regions of conserved synteny across all the fish species analyzed in this study.</p> <p>Conclusions</p> <p>The characterization of BES provided insights on the rainbow trout genome. The discovery of specific repeat elements will facilitate analyses of sequence content (e.g. for SNPs discovery and for transcriptome characterization) and future genome sequence assemblies. The numerous microsatellites will facilitate integration of the linkage and physical maps and serve as valuable resource for fine mapping QTL and positional cloning of genes affecting aquaculture production traits. Furthermore, comparative genomics through BES can be used for identifying positional candidate genes from QTL mapping studies, aid in future assembly of a reference genome sequence and elucidating sequence content and complexity in the rainbow trout genome.</p

Depression symptomatology and diagnosis: discordance between patients and physicians in primary care settings

<p>Abstract</p> <p>Background</p> <p>To examine the agreement between depression symptoms using an assessment tool (PHQ-9), and physician documentation of the same symptoms during a clinic visit, and then to examine how the presence of these symptoms affects depression diagnosis in primary care settings.</p> <p>Methods</p> <p>Interviewer administered surveys and medical record reviews. A total of 304 participants were recruited from 2321 participants screened for depression at two large urban primary care community settings.</p> <p>Results</p> <p>Of the 2321 participants screened for depression 304 were positive for depression and of these 75.3% (n = 229) were significantly depressed (PHQ-9 score ≥ 10). Of these, 31.0% were diagnosed by a physician with a depressive disorder. A total of 57.6% (n = 175) of study participants had both significant depression symptoms and functional impairment. Of these 37.7% were diagnosed by physicians as depressed. Cohen's Kappa analysis, used to determine the agreement between depression symptoms elicited using the PHQ-9 and physician documentation of these symptoms showed only slight agreement (0.001–0.101) for all depression symptoms using standard agreement rating scales. Further analysis showed that only suicidal ideation and hypersomnia or insomnia were associated with an increased likelihood of physician depression diagnosis (OR 5.41 P sig < .01 and (OR 2.02 P sig < .05 respectively). Other depression symptoms and chronic medical conditions had no affect on physician depression diagnosis.</p> <p>Conclusion</p> <p>Two-thirds of individuals with depression are undiagnosed in primary care settings. While functional impairment increases the rate of physician diagnosis of depression, the agreement between a structured assessment and physician elicited and or documented symptoms during a clinical encounter is very low. Suicidality, hypersomnia and insomnia are associated with an increase in the rate of depression diagnosis even when physician and self report of the symptom differ. Interventions that emphasize the use of routine structured screening of primary care patients might also improve the rate of diagnosis of depression in these settings. Further studies are needed to explore depression symptom assessment during physician patient encounter in primary care settings.</p

Temporal Network Based Analysis of Cell Specific Vein Graft Transcriptome Defines Key Pathways and Hub Genes in Implantation Injury

Vein graft failure occurs between 1 and 6 months after implantation due to obstructive intimal hyperplasia, related in part to implantation injury. The cell-specific and temporal response of the transcriptome to vein graft implantation injury was determined by transcriptional profiling of laser capture microdissected endothelial cells (EC) and medial smooth muscle cells (SMC) from canine vein grafts, 2 hours (H) to 30 days (D) following surgery. Our results demonstrate a robust genomic response beginning at 2 H, peaking at 12–24 H, declining by 7 D, and resolving by 30 D. Gene ontology and pathway analyses of differentially expressed genes indicated that implantation injury affects inflammatory and immune responses, apoptosis, mitosis, and extracellular matrix reorganization in both cell types. Through backpropagation an integrated network was built, starting with genes differentially expressed at 30 D, followed by adding upstream interactive genes from each prior time-point. This identified significant enrichment of IL-6, IL-8, NF-κB, dendritic cell maturation, glucocorticoid receptor, and Triggering Receptor Expressed on Myeloid Cells (TREM-1) signaling, as well as PPARα activation pathways in graft EC and SMC. Interactive network-based analyses identified IL-6, IL-8, IL-1α, and Insulin Receptor (INSR) as focus hub genes within these pathways. Real-time PCR was used for the validation of two of these genes: IL-6 and IL-8, in addition to Collagen 11A1 (COL11A1), a cornerstone of the backpropagation. In conclusion, these results establish causality relationships clarifying the pathogenesis of vein graft implantation injury, and identifying novel targets for its prevention

Dialysis and pediatric acute kidney injury: choice of renal support modality

Dialytic intervention for infants and children with acute kidney injury (AKI) can take many forms. Whether patients are treated by intermittent hemodialysis, peritoneal dialysis or continuous renal replacement therapy depends on specific patient characteristics. Modality choice is also determined by a variety of factors, including provider preference, available institutional resources, dialytic goals and the specific advantages or disadvantages of each modality. Our approach to AKI has benefited from the derivation and generally accepted defining criteria put forth by the Acute Dialysis Quality Initiative (ADQI) group. These are known as the risk, injury, failure, loss, and end-stage renal disease (RIFLE) criteria. A modified pediatrics RIFLE (pRIFLE) criteria has recently been validated. Common defining criteria will allow comparative investigation into therapeutic benefits of different dialytic interventions. While this is an extremely important development in our approach to AKI, several fundamental questions remain. Of these, arguably, the most important are “When and what type of dialytic modality should be used in the treatment of pediatric AKI?” This review will provide an overview of the limited data with the aim of providing objective guidelines regarding modality choice for pediatric AKI. Comparisons in terms of cost, availability, safety and target group will be reviewed

CMS physics technical design report : Addendum on high density QCD with heavy ions

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