1,725,164 research outputs found
Mandurama photograph collection [3183] [picture] /
No full textAlso available in an electronic version via the Internet at: http://nla.gov.au/nla.pic-an8526486-3183
Abstract 3183: Initial safety of AFP SPEAR T-cells in patients with advanced hepatocellular carcinoma
No full textAbstract Background: Genetically engineered affinity-enhanced autologous SPEAR T-cells (AFPc332T-cells) directed towards the HLA-A*02-restricted AFP peptide FMNKFIYEI are being tested in an ongoing Phase 1 trial to evaluate safety and antitumor activity in patients with hepatocellular carcinoma (HCC) (NCT03132792). Methods: This is a first-in-human study in HCC patients not amenable to transplant, resection, or loco-regional therapy and failed/intolerant/refused standard of care treatment. Patients must be HLA-A*02:01+ or 02:642+. Patients must have AFP expression by immunohistochemistry at ≥1+ in ≥20% HCC tumor cells or serum AFP ≥400 ng/ml and ≤5% IHC AFP in non-cancerous liver tissue. Up to 24 patients will be enrolled using a modified 3+3 design. Lymphodepletion is with fludarabine 20 mg/m2/day and cyclophosphamide 500 mg/m2/day on days -7 to -5. The initial transduced cell dose is 0.1×109 cells; additional doses are 1×109 and 5×109. Cohort expansion will occur at maximum tolerated dose and may allow doses up to 10×109 transduced cells. Dose-limiting toxicities (DLTs) are adjudicated by a Safety Review Committee. Results: As of 21Sep18, 2 patients were treated with 0.1×109 AFP SPEAR T-cells. Both had cytopenias related to lymphodepleting chemotherapy. Neither experienced cytokine release syndrome or SAEs during initial hospitalization. Liver chemistries show no AFPc332T-related hepatotoxicity. AFPc332T-cells were detected in both patients. One patient had grade 1 cognitive disturbance on day 8. This patient had SAEs of biliary obstruction at week 9 treated with stenting, and abdominal pain at week 12; neither was considered related to AFPc332T. Post-treatment imaging shows stable disease at week 12 by RECIST v1.1. Serum AFP was 12665 ng/ml at baseline, 29616 ng/ml at week 2, and 16,489 at week 12. Week 8 tumor biopsy showed diffuse tissue necrosis with cholestasis suspicious for necrotic tumor cells. No viable tissue was present. Immunostaining for CD3 showed numerous T-cells and T-cell aggregates within the necrotic tissue. The 2nd patient had no SAEs reported; post-treatment imaging is pending. Conclusions: AFP SPEAR T-cells at the 0.1×109 cell dose show no evidence of on target or off target toxicity in the first 2 patients. No protocol defined DLTs were reported. Current data support continued investigation of AFPc332T-cells. Updated data will be presented. Citation Format: Lipika Goyal, Matthew Frigault, Tim Meyer, Lynn G. Feun, Jordi Bruix, Anthony El-Khoueiry, Petr Hausner, Bruno Sangro, Theodore T. Pierce, Elliot Norry, Sulabha Ranganathan, Rafael G. Amado, Richard S. Finn. Initial safety of AFP SPEAR T-cells in patients with advanced hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3183
Gillan, Robert Lee, 1916-2009 (SC 3183)
Full text linkFinding aid and scan (Click on Additional Files below) for Manuscripts Small Collection 3183. Letter, 7 August 2006, of Robert Lee Gillan, Thorntown, Indiana, to Martha Harrison. He refers to his interest in genealogy and relates anecdotes about “Aunt Nancy,” an African American woman and caregiver to local families in Barren County, Kentucky. He includes particulars of some of her household advice, folk medicinal treatments and beliefs. He notes that she is buried in Lyons (Lyon) Cemetery
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
La Voz de Asturias : diario de información: Año XI Número 3183 - 1933 Junio 29
No full textCopia digital. España : Ministerio de Cultura y Deporte. Subdirección General de Cooperación BibliotecariaEste numero 3183 de 29 de junio no tiene pagina 7 y
Optimized synthesis of indole carboxylate metallo-beta-lactamase inhibitor EBL-3183
Full text linkA new synthetic route for the preparation of the metallo-β-lactamase inhibitor pre-candidate EBL-3183 was developed and carried out on a kilogram scale. The described process starts from a commercially available indole-2-carboxylate and employs an Ellman auxiliary approach coupled with ruthenium-catalyzed stereoselective reduction for the introduction of chirality. The key spirocyclic cyclobutane motif was assembled utilizing an epoxide building block, which was conveniently obtained in diastereomerically pure form. The amount and quality of the prepared final target EBL-3183 were sufficient for the preclinical studies
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