1,721,074 research outputs found
Validation of the Genetically-Defined DLBCL Subtypes and Generation of a Parsimonious Probabilistic Classifier
No full textDiffuse large B-cell lymphoma (DLBCL) is a clinically and molecularly heterogeneous disease with recognized transcriptional subtypes associated with normal cells of origin, activated B-cell (ABC) and germinal center B-cell (GCB) tumors. Emerging data suggested that additional heterogeneity existed, prompting us to comprehensively characterize genomic signatures of 304 newly diagnosed DLBCLs from patients treated with state-of-the-art therapy. We integrated recurrent mutations, somatic copy number alterations (SCNAs) and structural variants (SVs) and identified 5 genetically distinct DLBCL clusters (C1- C5 DLBCLs; Chapuy, Stewart, Dunford, et al. Nat Med 2018). Specifically, we identified two genetically distinct ABC subtypes, including favorable-risk C1 DLBCLs with features of extrafollicular origin and alterations also seen in transformed marginal zone lymphomas (NOTCH2 and NF-κB pathway member mutations and BCL6 SVs). Unfavorable-risk C5 ABC DLBCLs harbored frequent 18q/BCL2 copy gain and co-occurring CD79B and MYD88L265P mutations. We also identified two genetically distinct GCB subtypes, including unfavorable-risk C3 DLBCLs with frequent BCL2 SVs, mutations in chromatin-modifying enzymes (CREBBP, MLL2, EZH2) and BCR/PI3K signaling pathway members (including inactivating PTEN mutations and copy loss). Favorable-risk C4 GCB DLBCLs had frequent mutations in core and linker histones and signaling intermediates (SGK1, BRAF and STAT3). Additionally, we identified an ABC/GCB-independent subtype, C2 DLBCLs, characterized by frequent bi-allelic TP53 inactivation, 9p21.23/CDKN2A copy loss and associated genomic instability reflected in recurrent SCNAs, increased genome doublings and a distinct outcome following induction therapy. A next step in utilizing the characterized genetic substructure was to confirm it in an independent series and develop a molecular classifier that allows prospective identification of C1-C5 DLBCLs. To this end, we accessed whole exome sequencing, copy number and SV data from a recent cohort of newly diagnosed DLBCLs (39 tumor-normal pairs, 462 tumor-only samples; Schmitz et al. NEJM 2018). All samples were re-analyzed using our mutational and SCNA pipelines and our newly generated tumor-only algorithm (Chapuy, Stewart, Dunford, et al. Nat Med 2018) to avoid batch effects and harmonize the datasets. SVs were used as reported. Purity and ploidy were inferred using ABSOLUTE and samples with missing data or low purity were removed. For the combined cohort (579 samples), we assessed our previously characterized 158 genetic drivers (Chapuy, Stewart, Dunford, et al. Nat Med 2018) and confirmed equal distribution of their marginal frequencies (R=0.88, p=1.5e-51), excluding batch effects. Next, we applied non-negative matrix factorization (NNF) consensus clustering to the combined dataset (158 genetic drivers vs. 579 tumors) and confirmed the C1-C5 DLBCL genetic clusters. Notably, tumors from both series contributed at comparable frequencies to the respective C1-C5 DLBCLs. We also noted an enrichment of the alternative genetic labels from Schmitz et al. in 3 of our C1-C5 DLBCL subtypes (B2N in C1 DLBCLs, p<0.0001; EZB in C3 DLBCLs, p<0.0001; MCD in C5 DLBCLs, p<0.0001). These data confirmed the identity of the C1-C5 DLBCL clusters in an independent cohort. Next, we developed a molecular classifier that prospectively identified C1-C5 DLBCLs using a minimum number of easy-to-measure features. The NMF-defined classes of the combined cohort were used as gold-standard training and validation datasets. We tested different models for classification and selected an artificial neural network approach which provides accurate classification of individual samples and well-calibrated confidence metrics. To minimize potential overtraining, we developed a reduced input feature set of the 22 most discriminating features, constructed confidence metrics for each sample and trained an ensemble of Feed-Forward Neural Networks via 10-fold cross validation. With this approach, our classifier had 84% accuracy for the total set and 94% accuracy for the high-confidence samples (70% of all samples). The newly developed parsimonious classifier will allow prospective identification of the independently confirmed C1-C5 DLBCL subtypes in newly diagnosed patients, a necessity for clinical application. Disclosures Getz: Pharmacyclics: Research Funding; IBM: Research Funding; MuTect, ABSOLTUE, MutSig and POLYSOLVER: Patents & Royalties: MuTect, ABSOLTUE, MutSig and POLYSOLVER. Shipp:BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck & Co.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Research Funding; Gilead Sciences: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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