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O’Donoghue, Mark H. "Gould, Inc. v. Mitsui Mining & Smelting Co." American Journal of International Law 85, no. 1 (January 1991): 176–78. http://dx.doi.org/10.2307/2203570.
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In the course of litigation against an ex-employee, Gould, Inc. (Gould) allegedly learned that its proprietary technical data had been improperly supplied to Mitsui Mining & Smelting Co., Ltd. (Mitsui) and Miyakoshi Machine Tools Co., Ltd. (Miyakoshi), which then used those trade secrets in a joint venture with Pechiney Ugine Kuhlmann, a French state-owned company, and its wholly owned subsidiary, Trefimetaux (Pechiney/Trefimetaux). Gould filed a civil lawsuit against Pechiney/Trefimetaux, together with Mitsui and Miyakoshi, in U.S. district court, alleging violations of the Racketeer Influenced and Corrupt Organizations provisions of the Organized Crime Control Act of 1970 (18 U.S.C. §1961-1968 (1988)) (RICO). Gould’s complaint also included claims of unfair competition and unjust enrichment based upon the defendants’ alleged misappropriation of trade secrets. On the motion of Pechiney/Trefimetaux, the district court held that the civil RICO claim should be dismissed because, as “foreign states” under the Foreign Sovereign Immunities Act of 1976 (28 U.S.C. §1330, 1602-1611 (1988)) (FSIA), Pechiney and Trefimetaux were immune from criminal indictment for the acts alleged to have formed the basis for the RICO violation.
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Leigh, Monroe. "Gould Marketing, Inc. v. Ministry of Defence of Iran." American Journal of International Law 79, no. 1 (January 1985): 148–49. http://dx.doi.org/10.1017/s0002930000760854.
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Pintilie, Lucia, Amalia Stefaniu, Alina Ioana Nicu, Maria Maganu, and Miron Teodor Caproiu. "Design, Synthesis and Docking Studies of Some Novel Fluoroquinolone Compounds with Antibacterial Activity." Revista de Chimie 69, no. 4 (May 15, 2018): 815–22. http://dx.doi.org/10.37358/rc.18.4.6207.
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A new series of fluoroquinolone compounds have been obtained by Gould-Jacobs method. The compounds have been characterized by physic-chemical methods (elemental analysis, FTIR, NMR, UV-Vis) and by antimicrobial activity against Gram-positive and Gram-negative microorganisms. For the synthesized compounds have been performed calculations of characteristics and molecular properties, using Spartan�14 Software from Wavefunction, Inc. Irvine, CA. and molecular docking studies using CLC Drug Discovery Workbench 2.4 software, to identify and visualize the most likely interaction ligand (fluoroquinolone) with the receptor protein.
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Leigh, Monroe. "Ministry of Defense of the Islamic Republic of Iran v. Gould, Inc. No. CV 87-03673-RG." American Journal of International Law 82, no. 3 (July 1988): 591–94. http://dx.doi.org/10.2307/2202973.
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Wang, Jie, Adam S. Asch, Nada Hamad, Andrew Weickhardt, Monika Tomaszewska-Kiecana, Monika Dlugosz-Danecka, Halyna Pylypenko, et al. "A Phase 1, Open-Label Study of MGD013, a Bispecific DART® Molecule Binding PD-1 and LAG-3 in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma." Blood 136, Supplement 1 (November 5, 2020): 21–22. http://dx.doi.org/10.1182/blood-2020-139868.
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Background: MGD013 is an investigational, first-in-class, Fc-bearing bispecific tetravalent DART molecule designed to bind PD-1 and LAG-3 and sustain/restore the function of exhausted T cells (1). MGD013 demonstrates in vitro ligand blocking properties and improved T-cell responses beyond that observed with anti-PD-1 and anti-LAG-3 benchmark antibodies alone or in combination. PD-1 targeted therapy with nivolumab in patients (pts) with relapsed or refractory (R/R) diffuse large B cell lymphoma (DLBCL) has yielded modest efficacy (2). LAG-3, highly expressed in DLBCL (3), has emerged as another therapeutic target of interest in this population with continued unmet need. Methods: This study characterizes the safety, tolerability, dose-limiting toxicities, maximum tolerated dose, PK/PD, and antitumor activity of MGD013 in pts with advanced solid and hematologic malignancies. R/R DLBCL pts are being treated at the recommended Phase 2 dose of 600 mg every two weeks in Cohort Expansion. Results: At data-cutoff, 17 DLBCL pts received MGD013 (2.5 median prior lines of therapy, 41.2% with prior CAR-T therapy). Treatment-related adverse events (TRAEs) occurred in 11/17 (64.7%) pts, with no same TRAE occurring in > 1 patient except pyrexia (n=3). One grade ≥ 3 TRAE occurred (pneumonia), and no events of tumor lysis syndrome were observed. Among 11 response-evaluable pts (i.e. received at least one on-treatment scan), 1 complete response (CR) and 3 partial responses (PRs) per the Lugano Classification were observed. Analyses of available pre-treatment tumor biopsy samples corresponding to responding pts demonstrated relatively high levels of LAG-3, PD-1, and PD-L1 by IHC. More comprehensive translational analyses were undertaken for the pt with CR, observed after a single MGD013 infusion in a 28-year-old male in relapse 6 months after CD19-directed CAR T-cell therapy. In contrast to a pre-CAR T biopsy specimen demonstrating no LAG-3 or PD-1 expression, IHC analysis of a lymph node specimen biopsied post-CAR T and prior to MGD013 treatment revealed high levels of both LAG-3 and PD-1 on both infiltrating T-cells and malignant B-cells. Consistent with CD19 CAR T resistance, no CD19 expression was evident. MHC class II and PD-L1 expression were observed, which when bound to LAG-3 and PD-1, respectively, form immune checkpoints that can decrease T cell function. Following MGD013 treatment, serum IFN-γ markedly increased to >140-fold above baseline. No significant changes were observed for IL-6 or IL-2. Expansion of circulating CD3+CD8+ and CD3+CD4-CD8- T-cell subsets and associated cytolytic markers (i.e., perforin, granzyme B) were observed following MGD013 treatment. The patient underwent allogeneic stem cell transplant (allo-SCT) and remains in remission 14 months post-MGD013 and 12 months post-allo-SCT. Further correlative biomarker analyses are underway in the ongoing clinical trial. Conclusion: MGD013, a novel molecule designed to coordinately block PD-1 and LAG-3, has preliminarily demonstrated an acceptable safety profile and encouraging early evidence of anti-tumor activity in R/R DLBCL pts with and without prior treatment with CAR T. Biomarker analyses confirmed expression of both PD-1 and LAG-3 axes in responding pts with evidence of pharmacodynamic responses consistent with the ability of MGD013 to enhance T-cell function. References: 1. Luke JJ, Patel MR, Hamilton E, et al. A phase I, first-in-human, open-label, dose-escalation study of MGD013, a bispecific DART molecule binding PD-1 and LAG-3, in patients with unresectable or metastatic neoplasms. J Clin Oncol 38: 2020 (suppl; abstr 3004). 2. Keane C, Law SC, Gould C, et al. LAG3: a novel immune checkpoint expressed by multiple lymphocyte subsets in diffuse large B-cell lymphoma. Blood Adv. 2020;4(7):1367-1377. doi:10.1182/bloodadvances.2019001390 3. Ansell SM, Minnema MC, Johnson P, et al., Nivolumab for Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Patients Ineligible for or Having Failed Autologous Transplantation: A Single-Arm, Phase II Study. J Clin Oncol, 2019. 37(6): p. 481-489. Disclosures Wang: Verastem Oncology: Membership on an entity's Board of Directors or advisory committees; Curio Science: Honoraria; Putnam LLC: Honoraria. Asch:Astellas Pharma: Research Funding; Cartesian: Research Funding; Forty Seven: Research Funding; Juno: Research Funding; MacroGenics: Research Funding; MEI Pharma: Patents & Royalties: Provisional patent submitted (I), Research Funding. Hamad:Novartis: Honoraria; Abbvie: Honoraria. Weickhardt:Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Ipsen: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Ulahannan:Merck Co. Inc: Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; G1 Therapeutics, Inc.: Research Funding; ArQule, Inc.: Research Funding; Evelo Biosciences, Inc.: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Klus Pharma, Inc.: Research Funding; Isofol: Research Funding; GlaxoSmithKline GSK: Research Funding; Mersana Therapeutics: Research Funding; Macrogenics: Research Funding; Celgene Corporation: Research Funding; Boehringer Ingelheim: Research Funding; Array: Membership on an entity's Board of Directors or advisory committees; Ciclomed LLC: Research Funding; AbbVie, Inc.: Research Funding; AstraZeneca: Research Funding; Bristol-Myers Squibb: Research Funding; Syros: Membership on an entity's Board of Directors or advisory committees; Exelxis: Membership on an entity's Board of Directors or advisory committees. Koucheki:MacroGenics, Inc.: Current Employment, Current equity holder in publicly-traded company. Sun:MacroGenics, Inc.: Current Employment, Current equity holder in publicly-traded company. Li:MacroGenics, Inc.: Current Employment, Current equity holder in publicly-traded company. Chen:MacroGenics, Inc.: Current Employment, Current equity holder in publicly-traded company. Zhang:MacroGenics, Inc.: Current Employment, Current equity holder in publicly-traded company. Muth:MacroGenics, Inc.: Current Employment, Current equity holder in publicly-traded company. Kaminker:MacroGenics, Inc.: Current Employment, Current equity holder in publicly-traded company. Moore:MacroGenics, Inc.: Current Employment, Current equity holder in publicly-traded company. Sumrow:MacroGenics, Inc.: Current Employment, Current equity holder in publicly-traded company.
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Pietsch, H. P. "W. A. Gould: CGMP's/Food Plant Sanitation. 275 Seiten, zahlr. Abb. und Tab. CTI Publications Inc. Baltimore, MD, USA, 1990. Pries: 67, - U. S. $ (USA: 46, - $)." Food / Nahrung 35, no. 1 (1991): 111. http://dx.doi.org/10.1002/food.19910350133.
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Mahajan, S. "2006 Acta Materialia, Inc. Gold Medal." Acta Biomaterialia 1, no. 6 (November 2005): 591–92. http://dx.doi.org/10.1016/j.actbio.2005.08.002.
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Kudela, Ondřej, Vratislav Sedlák, and Vladimír Koblížek. "Different aspects of treatment of stable COPD according to GOLD 2017 strategy." Interní medicína pro praxi 19, no. 3 (July 1, 2017): 126–30. http://dx.doi.org/10.36290/int.2017.023.
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Felten, Sandra, Katrin Hartmann, Stefanie Doerfelt, Laura Sangl, Johannes Hirschberger, and Kaspar Matiasek. "Immunocytochemistry of mesenteric lymph node fine-needle aspirates in the diagnosis of feline infectious peritonitis." Journal of Veterinary Diagnostic Investigation 31, no. 2 (January 29, 2019): 210–16. http://dx.doi.org/10.1177/1040638718825280.
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Immunohistochemistry (IHC) of tissue samples is considered the gold standard for diagnosing feline infectious peritonitis (FIP), and, in cats without body cavity effusion, IHC is the only method available to establish definitive antemortem diagnosis. However, IHC requires invasive tissue sample collection. We evaluated sensitivity and specificity of an immunocytochemical assay of fine-needle aspirates (FNAs) of mesenteric lymph nodes that can be obtained noninvasively by ultrasound-guided aspiration to diagnose FIP. FNAs of mesenteric lymph nodes were obtained postmortem from 41 cats suspected of having FIP based on clinical and/or laboratory findings. FIP was confirmed immunohistochemically in 30 cats. In the other 11 cats, a disease other than FIP, which explained the clinical signs, was diagnosed histopathologically. Immunocytochemistry (ICC) was performed as an avidin–biotin complex method using a monoclonal anti-FCoV IgG 2A. Sensitivity, specificity, negative and positive predictive values (NPV, PPV, respectively) including 95% confidence intervals (95% CIs) were determined. ICC was positive in 17 of 30 cats with FIP, but also in 1 of 11 control cats that was diagnosed with lymphoma. Sensitivity of ICC was 53% (95% CI: 34–72); specificity 91% (95% CI: 59–100); NPV 42% (95% CI: 22–63); and PPV 94% (95% CI: 71–100). In a lethal disease such as FIP, specificity is most important in order to avoid euthanasia of unaffected cats. Given that a false-positive result occurred and FIP was correctly detected in only approximately half of the cases of FIP, ICC of mesenteric lymph node FNA alone cannot reliably confirm or exclude FIP, but can be a helpful test in conjunction with other diagnostic measures.
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Erber, Ramona, Arndt Hartmann, Peter Andreas Fasching, Matthias Ruebner, Robert Stöhr, Matthias Wilhelm Beckmann, Miriam Zentgraf, et al. "Reproducibility of mRNA-Based Testing of ESR1, PGR, ERBB2, and MKI67 Expression in Invasive Breast Cancer—A Europe-Wide External Quality Assessment." Cancers 13, no. 18 (September 21, 2021): 4718. http://dx.doi.org/10.3390/cancers13184718.
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Estrogen receptor (ER), progesterone receptor (PgR), Ki-67, and HER2 immunohistochemistry (IHC) together with HER2 in situ hybridization (ISH) are utilized to classify invasive breast cancer (IBC) into predictive molecular subtypes. As IHC evaluation may be hampered by analytical errors, gene expression assays could offer a reliable alternative. In this first Europe-wide external quality assessment (EQA) study, we investigated performance of mRNA-based Xpert® Breast Cancer STRAT4 (CE-IVD) in five European laboratories. The cohort comprised ten pre-therapy IBC core biopsies diagnosed in the coordinating center (CC). STRAT4 binary (positive or negative) mRNA results of each marker (ESR1, PGR, ERBB2, MKI67) were compared with the gold standard IHC/ISH performed by the CC. Sensitivity, specificity, and accuracy of ESR1 and ERBB2 mRNA were 100% for all samples. In contrast, PGR expression was falsely negative for one case by two sites and MKI67 falsely negative for two cases (respectively by four and one sites). These cases had STRAT4 expression values close to assay cut-offs and immunohistochemically presented heterogeneous low positive PgR and heterogeneous Ki-67. Our EQA shows that STRAT4 mRNA assay may be a reproducible method to evaluate ER, PgR, HER2, and Ki-67 status. However, cases with expression values close to assay cut-offs should be carefully reviewed.
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Tsao, Ming Sound, Kenneth Craddock, Guilherme Brandao, Zhaolin Xu, Wenda Greer, Yasushi Yatabe, Diana Ionescu, et al. "Canadian ALK (CALK): A pan-Canadian multicenter study to optimize and standardize ALK immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for ALK gene rearrangements." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 8096. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.8096.
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8096 Background: ALK gene rearrangement (ALK+) has been found in 3-5% of advanced non-small cell lung cancer patients. FISH is considered the “gold standard” for identification of ALK+ tumors, but its cost-effectiveness and adoption as a screening assay has been debated. Recent reports suggested that ALK IHC may serve as an alternative screening or possibly a diagnostic method. In this context, CALK was initiated to assess the feasibility of implementing ALK IHC and/or FISH assays across Canadian hospitals. Methods: FISH-confirmed 22 ALK+ and 6 ALK- tumors were used as study samples. Unstained sections and scanned images of HE-stained slides from each tumor block were distributed to participating centres. IHC protocols with best signal to noise ratio using the 5A4 (Novocastra) or ALK-1 (Dako) antibodies were developed for various auto-stainers and implemented to suit the existing conditions of the participating centres. A common FISH protocol using the ALK break-apart probe (Abbott Molecular, Chicago, IL) was developed based on published reports. H-score was used to assess IHC. FISH signals were scored in 100 tumor cells/case by 2-3 pre-trained persons. A second round IHC study using newly distributed slides was completed by 8 centres. Results: Independent IHC scores from 12 centres and FISH scores from 11 centres were collected and analysed. The intraclass correlation coefficients (ICC) between centres for IHC and FISH were 0.84 and 0.68, respectively. Following the analysis of initial IHC results, a second round study resulted in improved ICC of 0.94. One of 23 tumors revealed IHC-/FISH+ discrepancy, with the FISH revealing unusual signal configurations that suggested an atypical rearrangement. However, the sensitivity and specificity of FISH results across centres using the 15 aberrant signals cut-off ranged from 86.7-100% and 100%, respectively. Conclusions: Standardization across multiple centres for ALK testing by IHC and FISH can be achieved. IHC detected all FISH+ ALK tumors, except for one discrepant case with atypical FISH finding of unknown clinical implication. The study was supported by a Pfizer Canada grant.
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Xu-Monette, Zijun Yidan, Debrah Thompson, Bonnie LaFleur, Patrick Roche, Monica Reinholz, John Wineman, Ken H. Young, and Ihab Botros. "Diffuse Large B-Cell Lymphoma Cell of Origin Determination from Formalin-Fixed Paraffin-Embedded Tissues." Blood 126, no. 23 (December 3, 2015): 5052. http://dx.doi.org/10.1182/blood.v126.23.5052.5052.
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Abstract Diffuse large B-cell lymphoma (DLBCL) consists of two distinct subtypes, Germinal Center B-cell (GCB) and Activated B-Cell (ABC), each with distinct prognostic and biological profiles. With the advent of new targeted therapeutic approaches for DLBCL treatment, molecular sub-typing of the patient's tumor has been proposed as an important step in therapeutic selection and recommended by 2016 WHO classification guideline. Gene expression-profiling (GEP) based subtyping is considered the gold-standard method for DLBCL molecular sub-typing, but this method was established using fresh frozen / non-fixed tissues on microarray platforms. Since fresh tissue is not routinely collected during patient diagnosis, it severely limits the ability to utilize this assay in routine clinical practice. Multiple immunohistochemical (IHC) approaches have been developed to approximate the GEP methods, but these techniques generally suffer from lower than desired agreement rates with GEP classifications, and require staining of 4 to 8 sections of limited biopsy material. Interpretation of the slides can also be variable, leading to low inter-observer reproducibility. We have developed a 12 gene GEP-based DLBCL cell-of-origin (COO) assay using the HTG EdgeSeq System specifically designed to use a minimal amount of FFPE tissue. To build this system, we profiled a total of 107 samples previously subtyped using the HG-U133 Plus 2.0 Affymetrix microarrray and algorithm (Visco C et al Leukemia 2013); this algorithm was then validated in an additional 58 samples. The methodology we have developed produces 92% concordance with the microarray-based approach. Briefly, 107 DLBCL cases, of which 58 were previously sub-typed as ABC and 49 cases as GCB, were used as the training cohort. After classifier training and cross-validation, a separate cohort of 58 cases were used to verify the performance of the assay/classification system. Approximately 5 mm2 of 5 µm thick FFPE tissue was used to generate the data set for each of the cases. In addition to the DLBCL COO classification, the assay also contains additional genes including potential drug targets, T-cell, B-cell, and macrophage biomarkers, and housekeeping/normalization genes. These markers could be used to further understand the nature of the tumor and potentially help identify the characteristics of atypical tumors and immune infiltrates in the microenvironment. Disclosures Thompson: HTG Molecular Diagnostics, Inc: Equity Ownership. LaFleur:HTG Molecular Diagnostics, Inc: Equity Ownership. Roche:HTG Molecular Diagnostics, Inc: Equity Ownership. Reinholz:HTG Molecular Diagnostics, Inc: Equity Ownership. Wineman:HTG Molecular Diagnostics, Inc: Equity Ownership. Botros:HTG Molecular Inc: Equity Ownership.
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Trabucco, Sally E., Ethan S. Sokol, Jay A. Moore, Sophia Maund, Garrett M. Frampton, Vincent A. Miller, Jeffrey Venstrom, et al. "Prediction and Characterization of Diffuse Large B-Cell Lymphoma (DLBCL) Cell of Origin (COO) Subtypes Using Genomic Features from Targeted Next-Generation Sequencing." Blood 132, Supplement 1 (November 29, 2018): 1561. http://dx.doi.org/10.1182/blood-2018-99-116677.
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Abstract Introduction: DLBCL has two COO subtypes: Activated B Cell (ABC) and Germinal Center B cell (GCB). Patients with the ABC subtype have a poor prognosis compared to those with GCB, and COO can be predictive for response to some new therapeutic agents. Traditionally, COO subtype has been determined by microarray (ABC, GCB, unclassified), IHC-based algorithms (GCB or non-GCB), or expression-based Nanostring Lymph2Cx (ABC, GCB, unclassified). Some reports have failed to show a prognostic difference between GCB and non-GCB when employing IHC-based algorithms. This has led some to adopt the Lymph2Cx assay as the preferred method to assess COO, but in some cases the tumor content or RNA quality is inadequate to perform this assay. COO subtypes have differing gene mutations, with GCB typically characterized by EZH2 alterations and IGH:BCL2 translocations, while ABC is dominated by NF-KB and BCR signaling alterations such as MYD88 and CD79B short variants. Here we utilized mutational differences in COO subtypes to develop a COO DNA classification (COODC) model to predict COO from DNA-based features on a clinically utilized platform. Methods: Comprehensive genomic profiling (CGP) of DLBCL samples was performed using the DNA component of the FoundationOne® Heme platform; sequencing 465 genes for the GOYA trial (R-CHOP vs G-CHOP; N=499; NCT01287741), MAIN trial (R-CHOP +/- bevacizumab; N=44; NCT00486759), and cases from routine clinical care (FM-clinical; N=597). Gold standard COO classifications were determined in GOYA using the Lymph2Cx assay, and in MAIN using a modified Wright algorithm applied to a custom Nanostring expression panel. COODC was developed using a penalized lasso regression with 25-fold internal cross validation and cutoffs that optimize specificity and sensitivity. Concordance was calculated as the percentage of COODC calls matching the gold standard, excluding samples called unclassified in the gold standard or COODC. Results: We developed a novel DNA-based method to determine COO, which is 89% concordant with Lymph2Cx (Table) COODC was trained on 296 GOYA samples with Lymph2Cx COO calls and validated on 139 held-out samples from the same cohort (GOYA). Additional validation was performed on an independent first-line cohort (MAIN) and confirmed a high concordance (92%). COODC also provides prognostic value, confirming the worse prognosis of ABC (progression-free survival [PFS] hazard ratio [HR] 1.6; 95% confidence interval [CI]: 1.1-2.4; p=0.011) and unclassified (PFS HR 1.9; 95% CI: 1.1-3.2; p=0.021) compared with GCB. This approach also allows investigation into the genomics and underlying features of COO subtypes. Alterations in BCL2, EZH2, and TNFRSF14 were important determinants of the GCB phenotype, consistent with the enrichment of GCB samples among the EZB cluster in Schmitz et al. (N Engl J Med 2018), or C3 in Chapuy et al. (Nat Med 2018). Alterations in MYD88 and CD79B were highly predictive of ABC subtype, as expected. Alterations in NOTCH1, NOTCH2, and BCL6 were all slightly predictive of ABC subtype, despite the mixed phenotype of the BN2, N1 (Schmitz et al. N Engl J Med 2018), and C1 (Chapuy et al. Nat Med 2018) groups. Novel features include decreased average copy number of chromosome 6p, which encodes the HLA locus, in ABC (p=0.0064), and increased frequency of T>A and T>G alterations in GCB (p<0.0001 for both). We identified 2 major mutational signatures associated with COO: COSMIC signature 23, corresponding to a canonical activation-induced cytidine deaminase signature, enriched in ABC (p=0.002), and COSMIC signature 3, which trends to increased frequency in GCB (p=0.13). Conclusions: We have developed a new and clinically relevant method for determining DLBCL COO in specimens with tumor purity as low as 20%, without the need for RNA or matched normal tissue. This method is 89% (GOYA) to 92% (MAIN) concordant with the Lymph2Cx assay and maintains prognostic value. Integrating COO with CGP enables insights into disease biology, including the identification of novel features associated with COO. We identified a difference in mutational signatures between ABC and GCB, suggesting that different origin cells may contribute to different mutational processes. Disclosures Trabucco: Foundation Medicine Inc: Employment. Sokol:Foundation Medicine: Employment. Moore:Foundation Medicine, Inc.: Employment. Maund:Genentech: Employment. Frampton:Foundation Medicine Inc: Employment, Other: Employee and stockholder. Miller:Foundation Medicine: Employment, Other: Ownership interests none PLC*; Revolution Medicines: Membership on an entity's Board of Directors or advisory committees. Venstrom:Genentech Inc: Employment. Albacker:Foundation Medicine Inc: Employment; Foundation Medicine Inc: Employment. Sehn:Morphosys: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Roche/Genentech: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Oestergaard:Roche: Employment, Other: Ownership interests PLC. Bolen:Roche: Other: Ownership interests PLC*.
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Nunes, Cristiana Buzelin, Rafael Malagoli Rocha, Marcelo Araújo Buzelin, Débora Balabram, Fernanda de Souza Foureaux, Simone Souza Porto, and Helenice Gobbi. "False positivity in HER2 testing of breast cancer: novel paths for approaching an old dilemma." Journal of Clinical Pathology 66, no. 11 (July 18, 2013): 946–50. http://dx.doi.org/10.1136/jclinpath-2013-201647.
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AimsVariability in determining HER2 status has been reported, especially, differences in sensitivity and specificity among commercially available antibodies, with false positive and false negative results. We compared the sensitivity and specificity of five anti-HER2 antibodies by immunohistochemistry (IHC), using the new dual colour brightfield in situ hybridisation (DDISH) as the gold standard, on invasive breast carcinomas (IBC) arrays.Material and methodsSerial sections from tissue microarrays (TMA) containing 200 preselected primary IBC were submitted to DDISH (VENTANA INFORM HER2 Dual ISH assay), and immunohistochemistry, using Dako A0485 and HercepTest (polyclonal), Novocastra CB11 (mouse monoclonal), NeoMarkers SP3 and Ventana 4B5 (rabbit monoclonal).ResultsFrom the initial 200 cases, 184 were assessed by DDISH and IHC. The concordance among the antibodies was considered very good (kappa statistics varied from 0.82 to 0.9). The overall concordance between IHC and DDISH ranged from 94.1% for CB11 to 96.6% for A0485. The antibodies A0485, HercepTest, SP3 and 4B5 were over 95% sensitive and specific. CB11 was the most specific antibody (97.1%). 60% (CB11) to 83.3% (SP3) of the 2+ cases showed no gene amplification by DDISH. False negative cases varied from 0.5% (A0485) to 3.8% (CB11) of the cases, and false positive from 1.6% (CB11) to 2.7% (HercepTest, SP3 and 4B5) of the 184 cases.ConclusionsThere was very good agreement among the five anti-HER2 antibodies. CB11 was the most specific antibody, but showed more false negative cases. A0485, SP3, 4B5 and HercepTest were highly sensitive and specific, but showed more false positive cases.
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Qian, Xinyi. "Gold market price spillover between COMEX, LBMA and SGE." Journal of Economics and Finance 44, no. 4 (August 21, 2020): 810–31. http://dx.doi.org/10.1007/s12197-020-09517-5.
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Abstract In this paper, the author investigates spillover between the main markets from New York, London and Shanghai. Specific contract prices from the Commodity Exchange Inc. (COMEX), London Bullion Market Association (LBMA) and Shanghai Gold Exchange (SGE) were utilized. Results suggest that even with the increasing market influence of SGE, it still remains an isolated market, COMEX and LBMA maintain their dominant positions and act as the net spillover spreaders in the world gold market with almost equally strong market impacts.
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Adlim, Adlim, and Mohamad Abu Bakar. "PREPARATION OF CHITOSAN-GOLD NANOPARTICLES: PART 2. THE ROLE OF CHITOSAN." Indonesian Journal of Chemistry 8, no. 3 (June 17, 2010): 320–26. http://dx.doi.org/10.22146/ijc.21585.
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Colloidal gold nanoparticles prepared by employing chitosan as the stabilizer in solvent of methanol-acetic acid solution were stable for months without precipitation. The mole ratio of chitosan-gold ions of 5:1 - 30:1 gave dispersed and fine gold particles in range of 9.4-10.4 nm. Gold reduction in chitosan matrix was faster at higher chitosan concentration, and molar ratio of chi : Au, from 5:1 to 40:1. Higher acidity of acetic acid (pH 2-6) led to faster reduction of gold ions. The intensity of gold metal colloid plasmon band increased at higher concentration of acetic acid. Chitosan functioned both as a stabilizer and a reducing agent for gold ions. Gold colloidal particles immobilized on chitosan coated TiO2 as the solid support gave more dispersed and smaller particles (4.6 nm) compared with gold particles supported on TiO2 without chitosan coating. Keywords: gold nanoparticles, chitosan, chitosan coated TiO2
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Fitriyana, Fitriyana, and Fredy Kurniawan. "Polyaniline-Invertase-Gold Nanoparticles Modified Gold Electrode for Sucrose Detection." Indonesian Journal of Chemistry 15, no. 3 (November 12, 2015): 226–33. http://dx.doi.org/10.22146/ijc.21189.
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Sucrose sensor has been made by deposited the active materials on the surface of gold electrode. The active materials, i.e. polyaniline (PANI), invertase and gold nanoparticles, were deposited step by step. Aniline polymerization were conducted electrochemically at potential -500 to 1000 mV using voltammetry method with sweep rate 50 mV/s for 20 cycles in HCl solution pH 1.5. The modified electrode obtained was immersed in invertase 1 M phosphate buffer solution pH 6. The invertase trapping in polyaniline was performed using the same condition as aniline polymerization. Then, gold nanoparticles were deposited on the polyaniline-invertase modified gold electrode using Layer by Layer (LbL) technique. The polyaniline-invertase-gold nanoparticles modified gold electrode obtained was used to measure sucrose solution. Electrochemical signal of polyaniline (PANI)-invertase-gold nanoparticles modified gold electrode is increase with sucrose concentration. The sensitivity and detection limit of the electrode are 0.4657 µA mm-2 mM-1 and 9 µM, respectively. No electrochemical interference signals from fructose and glucose have been observed in the sucrose measurement.
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Bax, Dirk. "GOLD IS EARNED FROM THE PRODUCTION OF THAI GOLD LEAF." Indonesian Journal of Chemistry 1, no. 3 (June 5, 2010): 157–59. http://dx.doi.org/10.22146/ijc.21943.
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Thai people like to cover sacred objects or things dear to them with gold leaf.. Statues of Buddha are sometimes covered with so many layers of gold leaf that they become formless figures, that can hardly be recognized. Portraits of beloved ancestors, statues of elephants and grave tombs are often covered with gold leaf. If one considers the number of Thai people and the popularity of the habit, the amount of gold involved could be considerable.
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Polychronis, Georgios, Youssef S. Al Jabbari, Theodore Eliades, and Spiros Zinelis. "Galvanic coupling of steel and gold alloy lingual brackets with orthodontic wires: Is corrosion a concern?" Angle Orthodontist 88, no. 4 (March 6, 2018): 450–57. http://dx.doi.org/10.2319/092917-655.1.
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ABSTRACT Objectives: The aim of this research was to assess galvanic behavior of lingual orthodontic brackets coupled with representative types of orthodontic wires. Materials and Methods: Three types of lingual brackets: Incognito (INC), In-Ovation L (IOV), and STb (STB) were combined with a stainless steel (SS) and a nickel-titanium (NiTi) orthodontic archwire. All materials were initially investigated by scanning electron microscopy / x-ray energy dispersive spectroscopy (SEM/EDX) while wires were also tested by x-ray diffraction spectroscopy (XRD). All bracket-wire combinations were immersed in acidic 0.1M NaCl 0.1M lactic acid and neutral NaF 0.3% (wt) electrolyte, and the potential differences were continuously recorded for 48 hours. Results: The SEM/EDX analysis revealed that INC is a single-unit bracket made of a high gold (Au) alloy while IOV and STB are two-piece appliances in which the base and wing are made of SS alloys. The SS wire demonstrated austenite and martensite iron phase, while NiTi wire illustrated an intense austenite crystallographic structure with limited martensite. All bracket wire combinations showed potential differences below the threshold of galvanic corrosion (200 mV) except for INC and STB coupled with NiTi wire in NaF media. Conclusions: The electrochemical results indicate that all brackets tested demonstrated galvanic compatibility with SS wire, but fluoride treatment should be used cautiously with NiTi wires coupled with Au and SS brackets.
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Bassoriello, M. M. I., and K. S. Jordan. "First Report of Magnaporthe poae, Cause of Summer Patch Disease on Annual Bluegrass, in Canada." Plant Disease 96, no. 11 (November 2012): 1698. http://dx.doi.org/10.1094/pdis-06-12-0530-pdn.
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The ectotrophic, root-infecting fungus Magnaporthe poae Landschoot & Jackson, the causal agent of summer patch disease in the U.S. (2), is implicated in the damage and loss of annual bluegrass (Poa annua L.) on golf course greens. This pathogenic fungus, one of the important root pathogens of turfgrass, attacks and colonizes susceptible turfgrass roots suffering from environmental or cultural stresses. Over 100 turf samples that exhibited symptoms (chlorotic circular or irregular patches of ≥15 cm in diameter with necrotic crowns and discolored roots) reminiscent of summer patch were collected from 77 southwestern Ontario golf courses from July to August of 2009 and 2010. Roots and crowns were often covered with dark, ectotrophic runner hyphae, lobed hyphopodia, and growth cessation structures, characteristic of M. poae. Sections of root tissue were surface sterilized in 0.6% sodium hypochlorite (NaOCl) for 5 min. Sterilized root tissue was plated on potato dextrose agar (PDA) containing 50 mg L–1 streptomycin sulfate and incubated at 28°C for 7 to 10 days. A fungus with morphological characteristics (hyaline mycelium that appears gray or olive-brown when mature) similar to those of M. poae (1) was consistently isolated (≥100 isolates were obtained) and used to identify M. poae through molecular techniques and Koch's postulates. DNA was extracted from the fungal mycelium of the collected isolates using the PowerPlant DNA isolation kit (MO BIO Laboratories, Inc., Carlsbad, CA). The rDNA internal transcribed spacer (ITS) regions of the isolates (≥100 isolates) were amplified by PCR using universal fungal rDNA primers ITS 4 (5′-TCCTCCGCTTATTGATATGC-3′) and ITS 5 (5′- GGAAGTAAAAGTCGTAACAAGG-3′) (3). The purified PCR products were sequenced (GenBank Accession No. JX134588 through JX134601) and a BLAST search exhibited seven isolates with 99% (MAG3, MAG6, MAG13, MAG16, and MAG17) and 100% (MAG1 and MAG14) similarity to M. poae in the GenBank database. Pathogenicity of four isolates (MAG1, MAG3, MAG6, and MAG14) was confirmed with Koch's postulates. Sixteen healthy P. annua core samples (four replicates of each treatment/isolate) collected from an Ontario golf course were inoculated with 25 mg M. poae-infested Kentucky bluegrass seed (Poa pratensis L.; 12.5 mg inoculum applied at the surface of the potting medium and 12.5 mg inoculum applied on the foliar surface) and were placed in a growth chamber with 12-h day/night cycles at 30/25°C and approximate relative humidity. After 2 to 3 weeks, inoculated plants exhibited chlorotic foliage and necrotic roots covered with dark ectotrophic runner hyphae and lobed hyphopodia. Infected root sections from each replication were surface sterilized and placed on PDA containing 50 mg L–1 streptomycin sulfate. The fungal cultures exhibited morphological characteristics consistent with M. poae (1). To our knowledge, this is the first report of summer patch caused by M. poae in Canada. References: (1) B. B. Clarke and A. B. Gould, eds. Turfgrass Patch Diseases Caused by Ectotrophic Root-Infecting Fungi. The American Phytopathological Society, St. Paul, MN, 1993. (2) P. J. Landschoot and N. Jackson. Mycol. Res. 93:59, 1989. (3) T. J. White et al. Amplification and direct sequencing of fungal ribosomal RNA genes for phylogenetics. Pages 315-322 in: PCR Protocols: A Guide to Methods and Applications. M. A. Innis et al. eds. Academic Press, San Diego, CA, 1990.
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Adlim, Adlim, and Mohamad Abu Bakar. "PREPARATION OF CHITOSAN-GOLD NANOPARTICLES: PART 1 (OF 2). EFFECT OF REDUCING TECHNIQUE." Indonesian Journal of Chemistry 8, no. 2 (June 17, 2010): 184–88. http://dx.doi.org/10.22146/ijc.21621.
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Chitosan-stabilized gold nanoparticles were synthesized in aqueous formic acid, citric, or acetic acid with and without chitosan as the stabilizer. Refluxing in methanol, addition of hydrazine or sodium borohydride, photo-irradiation were employed as the reducing agents & reduction technique of gold ions. Dispersed particles of chitosan-stabilized gold were obtained in aqueous acetic acid-methanol solution. The chitosan-stabilized gold colloids (chi-Au) were dispersed and the particle size were in range of 9-30 nm, some of which were crystalline with various shapes. Chi-Au prepared with hydrazine as the reducing agent resulted in large and aggregated particles. The finest and dispersed chi-Au particles were obtained if NaBH4 was used as the reducing agent and the diameters could be controlled within 2.2-2.3 nm. Keywords: Gold nanoparticles, chitosan, size control
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MARCOUX, JEAN-MICHEL. "Beyond Gold Reserve Inc. v Bolivarian Republic of Venezuela: The Host State’s Capacity to Regulate Extractive Activities in Light of Canadian Firms’ Experience in International Investment Treaty Arbitration." Canadian Yearbook of international Law/Annuaire canadien de droit international 52 (October 2015): 261–95. http://dx.doi.org/10.1017/cyl.2015.13.
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AbstractIn a recent award involving Gold Reserve Inc., an international investment arbitral tribunal concluded that Venezuela had to pay compensation of US $713 million for violations of the fair and equitable treatment provision of an international investment agreement between Canada and Venezuela. This decision contrasts sharply with the outcome of other investment disputes concerning Canadian extractive companies. Relying on a detailed analysis of awards involving EnCana Corporation, Glamis Gold Ltd. and Vannessa Ventures Ltd., this article recalls that host states can take measures to increase the benefits and limit the negative impacts of extractive industries’ activities without breaching their obligations under international investment law.
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Aji, Abdul, Eko Sri Kunarti, and Sri Juari Santosa. "Synthesis of Gold Nanoparticles Using p-Aminobenzoic Acid and p-Aminosalicylic Acid as Reducing Agent." Indonesian Journal of Chemistry 19, no. 1 (January 29, 2019): 68. http://dx.doi.org/10.22146/ijc.26839.
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Synthesis of gold nanoparticles (AuNPs) by reduction of HAuCl4 with p-aminobenzoic acid and p-aminosalicylic acid as a reducing agent was investigated. This work was conducted in order to determine the optimum condition of AuNPs synthesis and examine the effect of the hydroxyl group in p-aminosalicylic acid towards the size, shape, and stability of the synthesized gold nanoparticles (AuNPs). The optimum condition of the gold nanoparticles synthesis was determined by UV/Vis spectrophotometer, the shape and size of gold nanoparticles were measured by Transmission Electron Microscope (TEM). The synthesis process was started by reacting HAuCl4 and the reducing agents in an aqueous solution at 86 ºC. The initial gold concentration, reducing agents concentration and pH were varied in order to obtain the optimum condition. In the optimum condition, the results showed that p-aminosalicylic acid containing both hydroxyl and amino groups performed higher reduction ability compared to p-aminobenzoic acid that only containing an amino group. Reducing agents which have a hydroxyl group (p-aminosalicylic acid) could produce AuNPs with a smaller concentration of HAuCl4 than p-aminobenzoic acid. Gold nanoparticles that were synthesized with p-aminosalicylic acid were more stable and had a smaller particle size compared to its counterpart that is synthesized with p-aminobenzoic acid.
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Hsiou, David, Chenlu Gao, Natalya Pruett, and Michael Scullin. "254 Validation of a Non-Wearable Sleep Tracking Device in Healthy Adults Under Normal and Restricted Sleep Conditions." Sleep 44, Supplement_2 (May 1, 2021): A102. http://dx.doi.org/10.1093/sleep/zsab072.253.
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Abstract Introduction Polysomnography (PSG) is the gold standard for measuring sleep, but this method is cumbersome, costly, and sometimes does not reflect naturalistic sleep patterns. Leading technology companies have developed non-wearable sleep tracking devices that have attracted public interest. However, the accuracy of these devices has either been shown to be poor or the validation tests have not been conducted by independent laboratories without potential conflicts of interest. Relative to PSG and actigraphy, and under conditions of both normal and restricted sleep, we assessed the accuracy of early and newer versions of a non-wearable sleep tracking device (Beddit, Apple Inc.). Methods Participants were 35 healthy young adults (Mage=18.97, SD=0.95 years; 77.14% female; 42.86% Caucasian). We randomly assigned them to go to bed at 10:30pm (normal sleep) or 1:30am (restricted sleep) in a controlled sleep laboratory environment. Lights-on was 7:00am for all participants. Sleep was measured by the early version (3.0) or newer version (3.5) of a non-wearable device that uses a sensor strip to measure movement, heart rate, and breathing. We also measured PSG, wristband actigraphy, and self-report. For each device, we tested accuracy against PSG for total sleep time (TST), sleep efficiency (SE%), sleep onset latency (SOL), and wake after sleep onset (WASO). Results While the early version displayed poor reliability (ICCs<0.30), the newer version of the non-wearable device yielded excellent reliability with PSG under both normal and restricted sleep conditions. Not only was agreement excellent for TST (ICC=0.96) and SE% (ICC=0.98), but agreement was also excellent for the notoriously difficult metrics of SOL (ICC=0.92) and WASO (ICC=0.92). This newer version significantly outperformed clinical grade actigraphy (ICCs often in the 0.40 to 0.75 range), and self-reported sleep (ICCs often below 0.40). Conclusion Surprisingly, a non-wearable device demonstrated greater agreement with PSG than clinical grade actigraphy. Though the field has generally been skeptical of commercial non-wearable devices, this independent validation provides optimism that some such devices would be efficacious for research in healthy adults. Future work is needed to test the validity of this device in older adults and clinical populations. Support (if any) National Science Foundation (1920730 and 1943323)
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Rini, Yuli Puspito, Agus Kuncaka, and Ngatidjo Hadipranoto. "Study of the Gold Extraction Using Tetra N-Butyl Ammonium Chloride-Chloroform." Indonesian Journal of Chemistry 1, no. 2 (June 3, 2010): 77–80. http://dx.doi.org/10.22146/ijc.21947.
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The existence of the AuCl4- ion in the solution as the function of pH before performing the extraction of gold in the system of tetra N-butylammonium chloride (TBACI) -chloroform has been studied. The experimental data showed that AuCl4- ion was hydrolyzed at pH 5-10 and, an amorf dark-brown precipitate was appeared at pH 11-14. Amount of gold in the solution at pH 14 before extraction was around 70%. Study of the extraction has been carried out by investigating the influence of pH and TBACI concentration on the extraction efficiency. The experimental result indicated that TBACI was very efficient extractant for the extraction of gold from aqueous halide with the efficiency higher than 99%. The extraction of Gold in the TBACI-chloroform was effective at pH 0-4 with minimum concentration of TBACI 10-3 M, and the calculated Kex (extraction constant) was 5.07x10-4.
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Pedrozo-Pupo, John Carlos, Gabriel Jesús Celemín-Güete, and Adalberto Campo-Arias. "Relación entre el índice de masa corporal y la frecuencia de exacerbaciones en pacientes con enfermedad pulmonar obstructiva crónica en Santa Marta, Colombia." Universidad y Salud 21, no. 2 (April 15, 2019): 127–31. http://dx.doi.org/10.22267/rus.192102.146.
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Introducción: El índice de masa corporal (IMC) se asocia inversamente a la frecuencia de exacerbaciones en pacientes con enfermedad pulmonar obstructiva crónica (EPOC); sin embargo, esta puede variar según el contexto. Objetivo: Cuantificar la asociación entre el IMC y la frecuencia de exacerbaciones en pacientes en Santa Marta, Colombia. Materiales y métodos: Estudio transversal de adultos con EPOC. Se calculó el IMC y la frecuencia de exacerbaciones se estimó a partir de la clasificación GOLD de estado global. Resultados: Participaron 292 pacientes entre 49 y 95 años; 61,6% eran hombres. Los IMC se observaron entre 12,8 y 40,2 (media=24,2; DE=4,5) distribuidos en 21 pacientes (7,2%) con desnutrición; 153 (52,4%), saludables; y 118 (40,4%), sobrepeso-obesidad. Un total de 146 pacientes (53,4%) se clasificaron GOLD A o B (exacerbaciones no frecuentes); y 136 pacientes (46,6%), GOLD C o D (exacerbaciones frecuentes). El 85,7% de los pacientes con desnutrición presentaron exacerbaciones frecuentes comparado con 51,6% en pacientes con peso saludable y 33,1% en pacientes con sobrepeso-obesidad (OR=0,18; IC95% 0,05-0,66 para peso saludable y OR=0,08; IC95% 0,02-0,29 para sobrepeso-obesidad frente a desnutrición). Conclusiones: El IMC presenta una relación inversa con la frecuencia de exacerbaciones en pacientes con EPOC de Santa Marta, Colombia.
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Shirazi, A. M., and L. H. Fuchigami. "Application of Processed Fiber for Nursery Crop Production." HortScience 33, no. 3 (June 1998): 523a—523. http://dx.doi.org/10.21273/hortsci.33.3.523a.
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Composted Tillamook Methane-digested dairy manure (processed fiber) plus woodwaste from landfills at Tillamook, Ore., was compared with Langerwerf, Calif., processed fiber amended with woodwaste from Tillamook, a mixture of peatmoss and pumice, and two commercial mixes from Black Gold Inc., Hubbard, Ore. Electrical conductivity, water-holding capacity, pH, cation exchange capacity, and mineral contents of Tillamook processed fiber with a mixture of wood waste were within the acceptable range for production of some nursery crops. Tillamook processed fiber with a mixture of wood waste media were favorable for the germination and growth of the lettuce and radish cultivars. The performance for seed germination was comparable to the performance of both Black Gold media and better than the other media. The growth of marigold `Bonanza Yellow', petunia `Plum Maddness', and salvia `Purple Sizzler' in Tillamook processed fiber wood media, supplemented with weekly feeding of fertilizer, was comparable to their growth in Black Gold media and better than the other media. The growth of `Double Delight' rose plants in Tillamook processed fiber wood media was similar to their performance in Black Gold media.
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McDonald, William C., Nilanjana Banerji, Kelsey N. McDonald, Bridget Ho, Virgilia Macias, and Andre Kajdacsy-Balla. "Steroidogenic Factor 1, Pit-1, and Adrenocorticotropic Hormone: A Rational Starting Place for the Immunohistochemical Characterization of Pituitary Adenoma." Archives of Pathology & Laboratory Medicine 141, no. 1 (May 19, 2016): 104–12. http://dx.doi.org/10.5858/arpa.2016-0082-oa.
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Context.—Pituitary adenoma classification is complex, and diagnostic strategies vary greatly from laboratory to laboratory. No optimal diagnostic algorithm has been defined. Objective.—To develop a panel of immunohistochemical (IHC) stains that provides the optimal combination of cost, accuracy, and ease of use. Design.—We examined 136 pituitary adenomas with stains of steroidogenic factor 1 (SF-1), Pit-1, anterior pituitary hormones, cytokeratin CAM5.2, and α subunit of human chorionic gonadotropin. Immunohistochemical staining was scored using the Allred system. Adenomas were assigned to a gold standard class based on IHC results and available clinical and serologic information. Correlation and cluster analyses were used to develop an algorithm for parsimoniously classifying adenomas. Results.—The algorithm entailed a 1- or 2-step process: (1) a screening step consisting of IHC stains for SF-1, Pit-1, and adrenocorticotropic hormone; and (2) when screening IHC pattern and clinical history were not clearly gonadotrophic (SF-1 positive only), corticotrophic (adrenocorticotropic hormone positive only), or IHC null cell (negative-screening IHC), we subsequently used IHC for prolactin, growth hormone, thyroid-stimulating hormone, and cytokeratin CAM5.2. Conclusions.—Comparison between diagnoses generated by our algorithm and the gold standard diagnoses showed excellent agreement. When compared with a commonly used panel using 6 IHC for anterior pituitary hormones plus IHC for a low-molecular-weight cytokeratin in certain tumors, our algorithm uses approximately one-third fewer IHC stains and detects gonadotroph adenomas with greater sensitivity.
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Park, Kye Won, Eun-Jae Lee, Jun Seong Lee, Jinhoon Jeong, Nari Choi, Sungyang Jo, Mina Jung, et al. "Machine Learning–Based Automatic Rating for Cardinal Symptoms of Parkinson Disease." Neurology 96, no. 13 (February 10, 2021): e1761-e1769. http://dx.doi.org/10.1212/wnl.0000000000011654.
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ObjectiveWe developed and investigated the feasibility of a machine learning–based automated rating for the 2 cardinal symptoms of Parkinson disease (PD): resting tremor and bradykinesia.MethodsUsing OpenPose, a deep learning–based human pose estimation program, we analyzed video clips for resting tremor and finger tapping of the bilateral upper limbs of 55 patients with PD (110 arms). Key motion parameters, including resting tremor amplitude and finger tapping speed, amplitude, and fatigue, were extracted to develop a machine learning–based automatic Unified Parkinson's Disease Rating Scale (UPDRS) rating using support vector machine (SVM) method. To evaluate the performance of this model, we calculated weighted κ and intraclass correlation coefficients (ICCs) between the model and the gold standard rating by a movement disorder specialist who is trained and certified by the Movement Disorder Society for UPDRS rating. These values were compared to weighted κ and ICC between a nontrained human rater and the gold standard rating.ResultsFor resting tremors, the SVM model showed a very good to excellent reliability range with the gold standard rating (κ 0.791; ICC 0.927), with both values higher than that of nontrained human rater (κ 0.662; ICC 0.861). For finger tapping, the SVM model showed a very good reliability range with the gold standard rating (κ 0.700 and ICC 0.793), which was comparable to that for nontrained human raters (κ 0.627; ICC 0.797).ConclusionMachine learning–based algorithms that automatically rate PD cardinal symptoms are feasible, with more accurate results than nontrained human ratings.Classification of EvidenceThis study provides Class II evidence that machine learning–based automated rating of resting tremor and bradykinesia in people with PD has very good reliability compared to a rating by a movement disorder specialist.
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Winthrop, K., D. Gold, D. Henrohn, L. Wang, A. Shapiro, H. Shi, G. Citera, and H. Schulze-Koops. "SAT0139 AGE-BASED (<65 VS ≥65 YEARS) INCIDENCE OF INFECTIONS AND SERIOUS INFECTIONS IN TOFACITINIB-, ADALIMUMAB- AND PLACEBO-TREATED PATIENTS WITH RHEUMATOID ARTHRITIS: A POST HOC ANALYSIS OF PHASE 2, PHASE 3 AND PHASE 3B/4 TOFACITINIB STUDIES." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1007–8. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1432.
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Background:Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). A recent ad hoc safety analysis (as of August 2019; may be subject to change) from an ongoing, open-label, randomised, post-authorisation safety study, Study A3921133 (NCT02092467), conducted in RA patients (pts) aged ≥50 years with ≥1 cardiovascular risk factor has shown that incidence rates (IRs) of serious infection events (SIEs) were higher with tofacitinib 10 mg BID vs tumour necrosis factor inhibitors (TNFi; adalimumab [ADA] and etanercept) and this difference was more pronounced in pts aged ≥65 years (Pfizer Inc; data on file).Objectives:To assess the IRs of overall infection events and SIEs in pts from Phase (P)2, P3 and P3b/4 tofacitinib RA trials which had a TNFi (ADA) active control or comparator arm.Methods:This is a post hoc analysis of Month 0–12 data pooled from P2 (A3921035;NCT00550446[first 12-week randomised parallel treatment period only]), P3 (ORAL Standard;NCT00853385) and P3b/4 (ORAL Strategy;NCT02187055) studies. Pts randomised to receive tofacitinib 5 mg BID, tofacitinib 10 mg BID, ADA 40 mg subcutaneously every other week and placebo (PBO) were included and assessed overall and by age (<65 or ≥65 years). SIEs were defined as infections requiring hospitalisation or parenteral antimicrobial therapy, or meeting other criteria for a serious adverse event. IRs (pts with events/100 pt-years of exposure [PY]) and 95% confidence intervals (CIs) were calculated for all infection events and SIEs; only the first infection events that occurred up to 28 days after the last dose or to the data cut-off date were considered.Results:Of 2180 pts included in the pooled studies (tofacitinib 5 mg BID: N=1064 [943.4 PY]; tofacitinib 10 mg BID: N=306 [236.6 PY]; ADA: N=643 [554.3 PY]; PBO: N=167 [108.1 PY]), 1841 (84.4%) were aged <65 years and 339 (15.6%) were aged ≥65 years. In general, the IRs for all infection events and SIEs were higher with tofacitinib 5 mg BID, tofacitinib 10 mg BID and ADA in pts aged ≥65 years compared with pts aged <65 years. Overall and when stratified by age, IRs for all infection events were similar across the active treatment groups (Figure 1); IRs with PBO were lower vs the active treatment groups overall and in pts aged <65 years, and numerically lower vs the active treatment groups in pts aged ≥65 years. IRs for SIEs were comparable across active treatment groups in pts aged <65 years, while among pts aged ≥65 years, IRs were numerically higher for tofacitinib 10 mg BID vs ADA, and appeared to be similar for tofacitinib 5 mg BID and ADA (Figure 2).Conclusion:In this analysis of data pooled from P2, P3 and P3b/4 tofacitinib RA studies which included a TNFi arm (ADA), the risk of SIEs or infections overall was similar for tofacitinib and ADA with the exception of a numerically higher rate of SIEs with tofacitinib 10 mg BID vs ADA in pts aged ≥65 years. In most countries, tofacitinib 10 mg BID is not an approved dose for the treatment of RA. This post hoc comparison is limited by variation in sample size and PY of exposure between treatment and age groups, and a small number of cases of SIEs in the ≥65-year age group resulting in wide 95% CIs; interpretation of results should be made with caution. The findings in the present analysis are consistent with increasing age being a known risk factor for infections.Acknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Christina Viegelmann of CMC Connect and funded by Pfizer Inc.Disclosure of Interests: :Kevin Winthrop Grant/research support from: Bristol-Myers Squibb, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Pfizer Inc, Roche, UCB, David Gold Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Dan Henrohn Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lisy Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Andrea Shapiro Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Harry Shi Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Gustavo Citera Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Hendrik Schulze-Koops Grant/research support from: Pfizer Inc
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Andreani, Agustina Sus, Suyanta Suyanta, Eko Sri Kunarti, and Sri Juari Santosa. "Synthesis of Citrate-Capped Gold Nanoparticles from Reduced [AuCl4]– on Ascorbic Acid-Immobilized Mg/Al Hydrotalcite." Indonesian Journal of Chemistry 18, no. 3 (August 30, 2018): 434. http://dx.doi.org/10.22146/ijc.30203.
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Reductive adsorption of [AuCl4]-– by using ascorbic acid immobilized on Mg/Al hydrotalcite (Mg/Al HT) and synthesis of gold nanoparticles (AuNPs) from the reduced gold using sodium citrate have been conducted. Mg/Al HT was synthesized by co-precipitation method at pH 10 with molar ratio of Mg(II) and Al(III) 2:1. Ascorbic acid (AA) was then immobilized on Mg/Al HT to form hybrid of AA and Mg/Al HT (Mg/Al HT-AA). Mg/Al HT-AA was used to reductively adsorb [AuCl4]– and the formed Au(0) was extracted by using sodium citrate to form citrate-capped AuNPs. The formation of AuNPs from 100 mg/L [AuCl4]– solution removed by 60 mg Mg/Al HT-AA was optimum at pH 5.0, by using 70 mM sodium citrate and 2 h sonication time. This optimum condition was successfully applied to synthesize AuNPs from [AuCl4]– as the leaching product of gold from PCB using aquaregia.
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Aji, Abdul, Sri Juari Santosa, and Eko Sri Kunarti. "Effect of Reaction Time and Stability Properties of Gold Nanoparticles Synthesized by p-Aminobenzoic Acid and p-Aminosalicylic Acid." Indonesian Journal of Chemistry 20, no. 2 (March 2, 2020): 413. http://dx.doi.org/10.22146/ijc.44674.
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In this work, we determined the influenced of the reaction time at the synthesis of gold nanoparticles (AuNPs) by p-aminosalicylic acid and p-aminobenzoic acid as reducing agent. Besides working as a reducing agent, the p-aminobenzoic acid and p-aminosalicylic acid also simultaneously played a role as a capping agent/stabilizing agent. Gold ion was first mixed with the pH adjusted p-aminobenzoic acid and p-aminosalicylic acid. The mixture then heated in boiling water at 86 °C. The formation of AuNPs was indicated by the appearance of red color and analyzed with UV/Vis spectrophotometry to evaluate their surface plasmon resonance (SPR) absorption in the wavelength range 400–800 nm. The reducing ability of the reducing agents was affected by its structure. Gold nanoparticles that were synthesized with p-aminosalicylic acid were more stable, faster and had a smaller size than its counterpart that is synthesized with p-aminobenzoic acid. The stability test over a periods 5 months showed that AuNPs were relatively stable.
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Fleischmann, R., B. Haraoui, M. H. Buch, D. Gold, G. Sawyerr, H. Shi, A. Diehl, and K. Lee. "POS0086 ANALYSIS OF DISEASE ACTIVITY MEASURES IN THE CONTEXT OF A METHOTREXATE WITHDRAWAL STUDY AMONG PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH TOFACITINIB 11 MG ONCE DAILY + METHOTREXATE: POST HOC ANALYSIS OF DATA FROM ORAL SHIFT." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 251.2–251. http://dx.doi.org/10.1136/annrheumdis-2021-eular.56.
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Background:The Phase 3b/4 study ORAL Shift demonstrated sustained efficacy and safety of tofacitinib modified-release (MR) 11 mg once daily (QD) following methotrexate (MTX) withdrawal that was non-inferior to continued tofacitinib + MTX use (per DAS28-4[ESR]), in patients (pts) with rheumatoid arthritis (RA) who achieved CDAI-defined low disease activity (LDA) with tofacitinib + MTX at Week (W)24.1Objectives:To assess the performance of alternative disease activity measures at W24 (randomisation) and W48 (study endpoint) in ORAL Shift.Methods:ORAL Shift (NCT02831855) enrolled pts aged ≥18 years with moderate to severe RA and an inadequate response to MTX. Pts received open-label tofacitinib MR 11 mg QD + MTX for 24 weeks. Achievement of CDAI LDA (≤10) at W24 was set as the criteria for entry to the 24-week double-blind MTX withdrawal phase, with pts randomised 1:1 to receive tofacitinib MR 11 mg QD + placebo (PBO) (ie blinded MTX withdrawal) or continue tofacitinib + MTX. In this post hoc analysis, efficacy analyses were performed in 8 subgroups defined by achievement of various disease activity criteria at W24: DAS28-4(ESR) remission (<2.6) or LDA (≤3.2); DAS28-4(CRP) <2.6 or ≤3.2; RAPID3 remission (≤3) or LDA (≤6); CDAI remission (≤2.8); and SDAI remission (≤3.3). For each subgroup, the proportion of pts who achieved the corresponding disease activity criterion at W48 was calculated, with a 95% confidence interval (CI) estimated using the normal approximation to the binomial distribution. The change (Δ) from W24 to W48 in least squares (LS) mean DAS28-4(ESR) and DAS28-4(CRP) was also calculated in each subgroup, with a 95% CI for the difference between treatment groups estimated using a mixed model with repeated measures. Nominal p values were calculated and are presented with no formal statistical hypothesis testing formulated.Results:Overall, 694 pts entered the open-label phase of ORAL Shift, and 530 were randomised and received treatment in the double-blind phase; 264 and 266 pts received tofacitinib + PBO and tofacitinib + MTX, respectively (Figure 1a). Considering those pts who were randomised and treated, the proportion of pts achieving each disease activity criterion at W24 varied, but was similar between treatments within each subgroup (Figure 1a). Among pts who met each disease activity criterion at W24, generally the majority of pts in both treatment groups also met the same criterion at W48 (Figure 1b). Numerically more pts receiving tofacitinib + MTX vs tofacitinib + PBO continued to meet the corresponding criterion at W48. Regardless of the disease activity criterion met at W24, differences between treatment groups in LS mean ΔDAS28-4(ESR) (Figure 1c) and ΔDAS28-4(CRP) (data not shown) from W24 to W48 favoured tofacitinib + MTX vs tofacitinib + PBO.Conclusion:This post hoc analysis of data from pts randomised and treated in ORAL Shift demonstrated that, regardless of the disease activity state criterion met at W24, generally a majority of pts receiving tofacitinib maintained achievement of the corresponding disease activity criterion at W48, with or without continued MTX. Differences between treatment groups in LS mean ΔDAS28-4(ESR) from W24 to W48, as defined by achievement of LDA or remission with a variety of disease activity measures, were less than a change of 1.2, which is considered to be the threshold for a minimal clinically important improvement.2References:[1]Cohen et al. Lancet Rheumatol 2019; 1: E23-34.[2]Ward et al. Ann Rheum Dis 2015; 74: 1691-1696.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Gemma Turner, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:Roy Fleischmann Speakers bureau: Pfizer Inc, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celltrion, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer Inc, Sanofi-Aventis, UCB, Grant/research support from: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celltrion, Eli Lilly, Genentech, GlaxoSmithKline, Janssen, Novartis, Pfizer Inc, Samumed, Sanofi-Aventis, UCB, VORSO, Boulos Haraoui Speakers bureau: Amgen, Pfizer Inc, UCB, Consultant of: AbbVie, Amgen, Eli Lilly, Merck, Pfizer Inc, UCB, Grant/research support from: AbbVie, Maya H Buch Speakers bureau: AbbVie, Consultant of: AbbVie, Eli Lilly, Gilead, MSD, Pfizer Inc, Roche, Sanofi, Grant/research support from: Pfizer Inc, Roche, UCB, David Gold Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Gosford Sawyerr Consultant of: Pfizer Inc, Employee of: Syneos Health Inc, Harry Shi Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Annette Diehl Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Kristen Lee Shareholder of: Pfizer Inc, Employee of: Pfizer Inc.
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Pietrzak-Johnston, S. M., H. Bishop, S. Wahlquist, H. Moura, N. De Oliveira Da Silva, S. Pereira Da Silva, and P. Nguyen-Dinh. "Evaluation of Commercially Available Preservatives for Laboratory Detection of Helminths and Protozoa in Human Fecal Specimens." Journal of Clinical Microbiology 38, no. 5 (2000): 1959–64. http://dx.doi.org/10.1128/jcm.38.5.1959-1964.2000.
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Formalin and mercuric chloride-based low-viscosity polyvinyl alcohol (LV-PVA) are widely used by most diagnostic parasitology laboratories for preservation of helminth eggs and protozoan cysts and trophozoites in fecal specimens. Concerns about the toxicity of formalin and the difficulty of disposal of LV-PVA are powerful incentives to use alternate preservatives. Such alternatives have been marketed by several companies and are often presented as one-vial, non-mercuric chloride fixatives that aim at performing the same role as formalin and PVA combined. We compared five, one-vial commercial preservatives, two from Meridian Diagnostics, Inc. (Ecofix and sodium acetate-acetic acid-formalin), and one each from Scientific Device Laboratories, Inc. (Parasafe), Alpha Tec Systems, Inc. (Proto-fix), and Streck Laboratories, Inc. (STF), with 10% formalin and LV-PVA. Fecal specimens obtained from patients in a Brazilian hospital were aliquoted within 12 h of collection into the seven preservatives mentioned above and were processed after 1 month at the Centers for Disease Control and Prevention. Direct and concentrated permanent smears as well as concentrates for 20 positive specimens (a total of 259 processed samples) were prepared, stained according to the manufacturers' instructions, examined, and graded. Positive specimens contained one or more parasites with stages consisting of eggs, larvae, cysts, and a few trophozoites of Giardia intestinalis. Criteria for assessment of the preservatives included the quality of the diagnostic characteristics of helminth eggs, protozoan cysts, and trophozoites, ease of use, and cost. Acceptable alternatives to formalin for wet preparations were found. Ecofix was found to be comparable to the traditional “gold standard” LV-PVA for the visualization of protozoa in permanent stained smears. This study suggests that more acceptable alternatives to the traditional formalin and LV-PVA exist.
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Fedorko, Daniel P., Esther C. Williams, Nancy A. Nelson, Leslie B. Calhoun, and Sizhuang S. Yan. "Performance of Three Enzyme Immunoassays and Two Direct Fluorescence Assays for Detection of Giardia lamblia in Stool Specimens Preserved in ECOFIX." Journal of Clinical Microbiology 38, no. 7 (2000): 2781–83. http://dx.doi.org/10.1128/jcm.38.7.2781-2783.2000.
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ECOFIX is a single-vial stool preservative that is both formalin- and mercury-free. We evaluated the abilities of three commercialGiardia lamblia-specific enzyme immunoassays (EIAs) (ProSpecT Giardia Microplate Assay [Alexon-Trend Inc.], Giardia Test [Techlab], and Premier Giardia lamblia [Meridian Diagnostics, Inc.]) and two commercial direct fluorescent-antibody (FA) assays for G. lamblia(Crypto/Giardia IF Test [Techlab] and Merifluor Cryptosporidium/Giardia [Meridian Diagnostics, Inc.]) to detectG. lamblia in 34 G. lamblia-positive and 44G. lamblia-negative stool specimens (determined by traditional examination for ova and parasites) preserved in ECOFIX compared to their abilities to detect G. lamblia in the same specimens preserved in formalin as the “gold standard” for each assay. Of the 34 formalin-fixed positive specimens, the number detected by each assay was as follows:, Alexon EIA, 34; Meridian EIA, 27; Techlab EIA, 29; Meridian FA assay, 31; and Techlab FA assay, 28. Both FA tests and the Alexon EIA performed well with ECOFIX, but the other two EIAs detected fewer positive specimens (the difference was statistically significant with the Techlab EIA) when ECOFIX was the preservative. Use of G. lamblia cyst antigen from cultured organisms preserved in formalin and ECOFIX demonstrated that the Alexon EIA could detect smaller amounts of antigen in ECOFIX than the other two EIAs could and suggested that cyst antigen is more stable in formalin. We recommend that laboratories use an FA assay or the Alexon EIA if they plan to use ECOFIX as their stool preservative.
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Lachaud, Alix, Adam Marcus, Slobodan Vučetić, and Ilija Mišković. "Study of the Influence of Non-Deposit Locations in Data-Driven Mineral Prospectivity Mapping: A Case Study on the Iskut Project in Northwestern British Columbia, Canada." Minerals 11, no. 6 (June 1, 2021): 597. http://dx.doi.org/10.3390/min11060597.
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The accuracy of data-driven predictive mineral prospectivity models relies heavily on the training datasets used. These models are usually trained using data for “known” deposit locations as well as “non-deposit” locations that are based on randomly generated point patterns. In this study, data related to the Seabridge Gold Inc Iskut project, an epithermal Au deposit in northwestern British Columbia (BC), Canada, are used to test the utility of data-driven mineral prospectivity modeling. The input spatial dataset is comprised mostly of publicly available data. Data for 18 vein and epithermal Au known mineral occurrences (KMO) are obtained from the BC Geological Survey’s MINFILE repository and selected as training deposit locations. A total of eleven sets of non-deposit locations (NDL) were also created, including one set of selected non-prospective KMO for Au deposits from the MINFILE and ten sets of random point patterns. Given the scale of this study, most of the KMO recorded on the property are of the epithermal deposit type. Hence, they could not be used as a selection criterion. Data-driven mineral potential models are generated using the random forest (RF) algorithm and trained on multiple data sets. The comparison of RF models demonstrated that using non-prospective KMO generates more accurate predictions than the random point pattern. The produced mineral prospectivity maps delineated multiple areas with higher discovery potential, which matched viable targets for the Au-Cu epithermal-porphyry system identified through previous Seabridge Gold Inc. (Toronto, ON, Canada) field reconnaissance and drilling programs.
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Helliwell, P., W. Tillett, R. Waxman, L. C. Coates, O. Fitzgerald, J. Packham, and N. Mchugh. "AB1241 EVALUATION OF A PATIENT COMPLETED DISEASE FLARE QUESTIONNAIRE IN PSORIATIC DISEASE." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1911.1–1912. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2791.
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Background:Psoriatic Disease (PsD) is a chronic inflammatory disease of the skin, nails, joints, and entheses. A number of composite disease activity measures have been developed though there is yet consensus as to which to use in the clinic and in clinical trials. A patient completed disease flare questionnaire, covering multiple domains of disease impact, has been developed but has yet to be fully validated.Objectives:To validate the FLARE questionnaire in PsD.Methods:The 10 question FLARE instrument1was administered to 141 patients in an observational study of treatment change in PsD over 6 months follow up. Disease activity was measured by the PASDAS and the gold standard of flare was based on patient opinion. ROC curve was constructed to examine the optimum cut-off for disease flare. Agreement between the FLARE instrument and patient opinion was assessed by Cohen’s kappa. Test-retest was assessed in 28 patients with stable disease who underwent repeat assessment within 2 weeks and evaluated by intra-class correlation coefficient (ICC).Results:The FLARE questionnaire was administered at 367 patient encounters. ROC analysis indicated that the optimum cut-off for a flare of disease was 4 (sensitivity 82%, specificity 76%; area under curve 0.85: figure). Mean PASDAS scores were 2.7 and 6.3 for no-flare (4) and flare (≥4) respectively (p = < 0.0001). For those patients who were having a flare the frequency of response to each question is given in the table. Agreement between patient opinion and questionnaire was 0.57, and between patient opinion and physician (based on treatment escalation) 0.43. ICC for the questionnaire was 0.87 (95% CI 0.72 – 0.94).Conclusion:In PsD a flare represents escalation of symptoms and signs across multiple domains, as measured by the FLARE instrument; a score of 4 or more has external validity both in terms of composite disease activity and overall patient opinion of the state of their condition.References:[1]Moverley A, Waxman R, de Wit M, Parkinson A, Campbell W, Brooke M, et al J Rheum May 2016, 43 (5) 974-978TableFLARE item response for those in flare vs not in flareItemFLARE instrument score <4FLARE instrument score ≥4N (%)N (%)Worsening Itch35 (19)108 (58)Worsening skin area27 (15)91 (49)Increasing joint pain34 (19)161 (86)Increasing number of tender joints20 (11)142 (76)Decrease in ability to perform activities3 (2)81 (43)Worsening in ability to move easily8 (4)126 (67)Increase in frustration14 (8)142 (76)Worsening in depression8 (4)90 (48)Worsening in feeling of tiredness all the time37 (21)148 (79)Worsening in the number or combination of symptoms from your disease7 (4)134 (72)Figure.ROC analysis of FLARE questionnaireAcknowledgments:This report is independent research funded by the National Institute for Health Research, Programme Grants for Applied Research [Early detection to improve outcome in patients with undiagnosed PsA (‘PROMPT’), RP-PG-1212-20007]. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social CareDisclosure of Interests:Philip Helliwell: None declared, William Tillett Grant/research support from: AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, Consultant of: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, MSD, Pfizer Inc, UCB, Speakers bureau: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, Pfizer Inc, UCB, Robin Waxman: None declared, Laura C Coates: None declared, Oliver FitzGerald: None declared, Jon Packham: None declared, Neil McHugh: None declared
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Li, Xiaona, Suhua Zheng, Suiyue Pan, Ting Yan, Jie Di, Yinian Yang, and Jinluo Cheng. "Accuracy Evaluation of Five Blood Glucose Monitoring Systems in Patients from Different Departments." Experimental and Clinical Endocrinology & Diabetes 128, no. 04 (April 30, 2019): 210–15. http://dx.doi.org/10.1055/a-0855-3726.
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Abstract Background Self-monitoring of blood glucose (SMBG) systems are expected to be accurate and provide reliable results. The international standard ISO (International Organization for Standardization) 15197:2013 is widely accepted for the accuracy evaluation for SMBG systems. Accuracy evaluation was performed for 5 different SMBG systems in patients from multi-departments at the hospital. Method A total of 120 patients from Changzhou Second People’s Hospital (Changzhou, China) were randomized and enrolled in the study. Accuracy evaluation was performed for 5 different SMBG systems: Gold AQ (Sinocare), Freestyle Optium Xceed (Abbott), Contour TS (Bayer), OneTouch Ultra (J&J) and Accu-Chek Performa (Roche). For each system, comparison measurements were performed with YSI 2300 STAT PLUS Glucose and Lactate Analyzer and Roche Cobas 8000 Modular Analyzer. Results All 5 systems showed that 100% of results fall within consensus error grid Zones A and B. Compared with YSI 2300 or Roche Cobas 8000 Modular Analyzer, Gold AQ system showed the highest accuracy. The linearity analysis also showed that Gold AQ had the highest correlation coefficient. Conclusion Compared with other SMBG systems, Gold AQ Glucose Monitoring System manufactured by Sinocare Inc. had the highest accuracy in measuring blood glucose level in patients from multi-departments at this hospital.
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Bullock, M., C. O'Neill, A. Chou, A. Clarkson, T. Dodds, C. Toon, M. Sywak, et al. "Utilization of a MAB for BRAFV600E detection in papillary thyroid carcinoma." Endocrine-Related Cancer 19, no. 6 (September 20, 2012): 779–84. http://dx.doi.org/10.1530/erc-12-0239.
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Identification of BRAFV600E in thyroid neoplasia may be useful because it is specific for malignancy, connotes a worse prognosis, and is the target of novel therapies currently under investigation. Sanger sequencing is the ‘gold standard’ for mutation detection but is subject to sampling error and requires resources beyond many diagnostic pathology laboratories. In this study, we compared immunohistochemistry (IHC) using a BRAFV600E mutation-specific MAB to Sanger sequencing on DNA from formalin-fixed paraffin-embedded tissue, in a well-characterized cohort of 101 papillary thyroid carcinoma (PTC) patients. For all cases, an IHC result was available; however, five cases failed Sanger sequencing. Of the 96 cases with molecular data, 68 (71%) were BRAFV600E positive by IHC and 59 (61%) were BRAFV600E positive by sequencing. Eleven cases were discordant. One case was negative by IHC and initially positive by sequencing. Repeat sequencing of that sample and sequencing of a macrodissected sample were negative for BRAFV600E. Of ten cases positive by IHC but negative by sequencing on whole sections, repeat sequencing on macrodissected tissue confirmed the IHC result in seven cases (suggesting that these were false negatives of sequencing on whole sections). In three cases, repeat sequencing on recut tissue remained negative (including using massive parallel sequencing), but these cases demonstrated relatively low neoplastic cellularity. We conclude that IHC for BRAFV600E is more sensitive and specific than Sanger sequencing in the routine diagnostic setting and may represent the new gold standard for detection of BRAFV600E mutation in PTC.
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Madathiveetil, Suma, Jisha Kalathil Thodiyil, and Freena Rose. "Comparison of Grading and ER, PR Hormone Receptor Status of Carcinoma Breast in FNAC with Histopathology - A Cross Sectional Study from Thrissur, Kerala." Journal of Evidence Based Medicine and Healthcare 8, no. 21 (May 24, 2021): 1696–700. http://dx.doi.org/10.18410/jebmh/2021/320.
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BACKGROUND Breast cancer is now the most common cancer in cities in India and 2 nd most common cancer in the rural areas. Fine needle aspiration cytology (FNAC) is a less invasive pre-operative diagnostic method and is preferred over core / excision biopsy to decide the benign or malignant nature of the breast lump. Prognostic factor assessment by FNAC would allow the identification of patients who would benefit from neo adjuvant treatment (patients with grade 3 tumours) and in whom conservation surgery is inadvisable.1 The purpose of this study is to compare the grades of breast cancer in FNAC with histopathology as gold standard and compare the oestrogen (ER) and progesterone (PR) hormonal expression pattern on immunocytochemistry (ICC) with immunohistochemistry (IHC). From this study we intend to assess the usefulness of cytological grading and ER, PR hormone receptor status pre-operatively so that hormonal therapy can be included with neoadjuvant chemotherapy. METHODS This is a cross sectional study with a sample size of 50, conducted in the Department of Pathology. RESULTS Out of 50 cases, maximum number of patients were in the age group of 51 - 60 years. 68 % had attained menopause; 69 % of patients had tumour size between 2 - 5 cm and 90 % of tumours were in the upper outer quadrant of breast. Considering hormonal expression, in case of ER there was a moderate agreement between ICC and IHC (κ = .428, P = 0.005) and no agreement was seen in case of PR (κ = .073, P = 0.625). Regarding the cytological grading, this study showed highest degree of concordance with grade II tumours with a sensitivity of 75.9 %. For Grade I it was 2.5 % and for grade III, it was 33.3 %. CONCLUSIONS Evaluation of hormonal status and nuclear grading is fairly reliable on cytology when performed on qualitatively superior FNAC material from the primary breast lesions. KEYWORDS Carcinoma Breast, FNAC, ER / PR, Immunocytochemistry, Immunohistochemistry, Cytological Nuclear Grading
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Berry, David B., Ana E. Rodríguez-Soto, Jana R. Tokunaga, Sara P. Gombatto, and Samuel R. Ward. "An Endplate-Based Joint Coordinate System for Measuring Kinematics in Normal and Abnormally-Shaped Lumbar Vertebrae." Journal of Applied Biomechanics 31, no. 6 (December 2015): 499–503. http://dx.doi.org/10.1123/jab.2015-0008.
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Vertebral level-dependent, angular, and linear translations of the spine have been measured in 2D and 3D using several imaging methods to quantify postural changes due to loading conditions and tasks. Here, we propose and validate a semiautomated method for measuring lumbar intervertebral angles and translations from upright MRI images using an endplate-based, joint coordinate system (JCS). This method was validated using 3D printed structures, representing intervertebral discs (IVD) at predetermined angles and heights, which were positioned between adjacent cadaveric vertebrae as a gold standard. Excellent agreement between our measurements and the gold standard was found for intervertebral angles in all anatomical planes (ICC > .997) and intervertebral distance measurements (ICC > .949). The proposed endplate-based JCS was compared with the vertebral body-based JCS proposed by the International Society of Biomechanics (ISB) using the 3D printed structures placed between 3 adjacent vertebrae from a cadaver with scoliosis. The endplate-based method was found to have better agreement with angles in the sagittal plane (ICC = 0.985) compared with the vertebral body-based method (ICC = .280). Thus, this method is accurate for measuring 3D intervertebral angles in the healthy and diseased lumbar spine.
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Tao-Cheng, J. H., and V. A. Tanner. "A modified method of pre-embedding EM immunocytochemistry which improves specificity and simplifies the process for in vitro cells." Proceedings, annual meeting, Electron Microscopy Society of America 52 (1994): 306–7. http://dx.doi.org/10.1017/s0424820100169262.
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EM Immunocytochemistry (ICC) localizes specific antigens at the subcellular level. We present here a modified method to process in vitro cells for pre-embedding EM ICC. The first advantage of this method is that it uses multiwell plastic chamber slides for cell cultures, and offers (a) excellent light microscopic images for precise monitoring of the cells and ICC staining throughout the procedure, including the final embedded Epon block, (b) efficiency in EM processing, especially the ease of removing the slide from the Epon blocks after polymerization, and (c) convenience of carrying out many different experimental conditions such as fixative composition and antibody dilutions on the same multichamber slide. The second advantage of this method is the use of a 1.4 nm gold probe which is covalently bound to the secondary antibody, and gives (a) precise localization of the antigenic sites in the form of individual silver grains which do not obscure the underlying fine structure, and (b) higher sensitivity and specificity of the ICC staining because the covalent conjugation of the gold to the secondary antibody is very stable and is not easily displaced.
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Nichols, Richard John. "The Influence of Intermetallic Compounds, (IMC), on High Speed Shear Testing with a Specific Interest in Electroless Palladium / Autocatalytic Gold." Additional Conferences (Device Packaging, HiTEC, HiTEN, and CICMT) 2017, DPC (January 1, 2017): 1–43. http://dx.doi.org/10.4071/2017dpc-tha1_presentation4.
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Increasing IO counts have led to ever increasing solder performance expectations. A predominant measure of solder joint integrity is gained through HSS testing. This article will statistically evaluate the solderability of final finishes after substrate and IMC ageing. Lead free solder balls will be used in this exercise to simulate lead free production. The finishes selected are: Immersion tin, Organic Surface Protection (OSP), Electroless Nickel/ Immersion Gold (ENIG), Electroless Nickel /Electroless Palladium and Immersion Gold (ENEPIG) and Electroless Palladium / semi Autocatalytic Gold (EPAG). Where necessary, the adaptions of the final finishes will be included for testing. An example of this is ENEPIG with thin nickel. This is a measure to enable high frequency and or improve flexibility. For the purpose of the paper, the evaluation will endeavor to relate HSS performance and physical and chemical characteristics of the related deposit layer. To ensure that a comparative analysis is possible, an “as received” (ASR) population will be used as a base line. This fully data driven evaluation will aim to increase the understanding of key indicators that can ensure good quality soldering performance. In the field, there are assertions that the IMC is a good indicator of the solder joint integrity. However this is usually as far as this particular statement is taken. A key question that is still outstanding is what particular attribute of the IMC is important for solder joint reliability. The shape and size of the IMC is often cited as crucial to quality assurance. Such indicators may be valid but this study will couple this kind of observation with elemental quantification (EDX), high resolution microscopy and finally mechanical failure techniques. A comprehensive test plan will be executed to more fully understand the role of IMC formation in terms of solder joint reliability, (SJR).
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Kakkar, F., UD Allen, D. Ling, M. Pai, and IC Kitai. "Tuberculosis in Children: New diagnostic Blood Tests." Canadian Journal of Infectious Diseases and Medical Microbiology 21, no. 4 (2010): e111-e115. http://dx.doi.org/10.1155/2010/129616.
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The interferon-gamma-release assays were developed to overcome the pitfalls and logistic difficulties of the tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection (LTBI). These blood tests measure the in vitro production of interferon-gamma by sensitized lymphocytes in response toMycobacterium tuberculosis-specific antigens. Two interferon-gamma-release assays are registered for use in Canada: the QuantiFERON-TB Gold In-Tube assay (Cellestis Inc, Australia) and the T.SPOT–TB test (Oxford Immunotec, United Kingdom). Evaluation of these tests has been hampered by the lack of a gold standard for LTBI, and limited paediatric data on their use. It appears that they are more specific than the TST, and may be useful for evaluating TST-positive patients at low risk of true LTBI. Moreover, they may add sensitivity if used in addition to the TST in immunocompromised patients, very young children and close contacts of infectious adults. A summary of these tests, their limitations and their application to clinical paediatric practice are described.
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Ye, Y., X. Yue, W. Krueger, and L. Wegrzyn. "POS1163 CHARACTERISTICS AND OUTCOMES IN A REAL-WORLD COHORT OF RHEUMATOID ARTHRITIS PATIENTS WITH COVID-19." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 860.1–860. http://dx.doi.org/10.1136/annrheumdis-2021-eular.565.
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Background:While some risk factors for severe COVID-19 outcomes have been identified for the general population and patients with rheumatic diseases (1-3), what drives these outcomes in specific rheumatic disease remains unclear. In addition, these findings need to be assessed across various observational data sources to ensure external validity.Objectives:To describe the demographics, comorbidities, and severe COVID-19 outcomes among rheumatoid arthritis (RA) patients infected with SARS-CoV-2 in the United States.Methods:A large nationwide electronic health record database (Optum, Inc.) in the United States, with data range between February 1, 2020 and September 17, 2020, was used to describe the demographics, comorbidities, and severe COVID-19 outcomes of RA patients with confirmed COVID-19 diagnosis (diagnosis for COVID-19 or positive PCR or antigen test). Patients with a single diagnosis of RA (ICD-10 code) before the diagnosis of COVID-19 were included. Patients missing age or sex, under 18 years of age on COVID-19 diagnosis date, or having less than 15 months of activity prior to COVID-19 diagnosis in the data source were excluded. We described demographics, comorbidities, and severe COVID-19 outcomes, including death, hospitalization, ICU admission, and acute respiratory insufficiency (ARI) identified between 14 days prior to and 30 days after COVID-19 diagnosis. Mean and standard deviation (SD) was reported for continuous variables. For categorical variables, count (N) and proportion was reported.Results:We identified 2,948 patients diagnosed with RA and infected with SARS-CoV-2 (mean age± SD: 62 years ± 16, 77% female, 68% white). Of all identified patients, 38% were current or former smokers. For the 2,614 patients with BMI recorded, 78% were overweight or obese (mean BMI±SD: 31.2±8.3). The mean Charlson comorbidity index (CCI) was 3.6 (SD 3.2), with 87% of the study cohort having one or more comorbid condition, including hypertension (55%), type 2 diabetes (26%), COPD (20%), moderate to severe asthma (17%), coronary artery disease (17%), chronic kidney disease (13%), and heart failure (13%). Severe COVID-19 outcomes occurred in 618 (21%) patients. Among all RA patients with COVID-19, 137 patients (4.6%) experienced ARI, 484 patients (16.4%) were hospitalized (including 174 (5.9%) admitted to the ICU), and 155 patients (5.3%) died.Conclusion:Underlying medical conditions that are known or possible risk factors of severe illness from SARS-CoV-2 infection in the general population are common in this RA cohort from a large national EHR database. However, whether patients with RA are more vulnerable to severe COVID-19 outcome than the general population requires adjustment by age and other important confounders.References:[1]Gianfrancesco M, Hyrich KL, Al-Adely S, Carmona L, Danila MI, Gossec L, et al. Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry. Ann Rheum Dis. 2020;79(7):859-66.[2]Williamson EJ, Walker AJ, Bhaskaran K, Bacon S, Bates C, Morton CE, et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature. 2020;584(7821):430-6.[3]Gold JAW, Wong KK, Szablewski CM, Patel PR, Rossow J, da Silva J, et al. Characteristics and Clinical Outcomes of Adult Patients Hospitalized with COVID-19 - Georgia, March 2020. MMWR Morb Mortal Wkly Rep. 2020;69(18):545-50.Disclosure of Interests:Yizhou Ye Shareholder of: AbbVie Inc. and Pfizer Inc., Employee of: AbbVie Inc., Xiaomeng Yue Employee of: AbbVie Inc., Whitney Krueger Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Lani Wegrzyn Shareholder of: AbbVie Inc., Employee of: AbbVie Inc.
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Alimin, Alimin, Narsito Narsito, Indriana Kartini, and Sri Juari Santosa. "Retracted-Enhanced X-Ray Absorption Property of Gold-Doped Single Wall Carbon Nanotube." Indonesian Journal of Chemistry 15, no. 3 (November 12, 2015): 211–17. http://dx.doi.org/10.22146/ijc.21187.
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Enhanced X-ray absorption property of single wall carbon nanotube (SWCNT) through gold (Au) doping (Au@SWCNT) has been studied. Mass attenuation coefficient of SWCNT increased 5.2-fold after Au doping treatment. The use of ethanol in the liquid phase adsorption could produce Au nanoparticles as confirmed by the X-ray Diffraction (XRD) patterns. The possibility of gold nanoparticles encapsulated in the internal tube space of SWCNT was observed by transmission electron microscope technique. A significant decrease of nitrogen uptakes and upshifts of Radial Breathing Mode (RBM) of Au@SWCNT specimen suggest that the nanoparticles might be encapsulated in the internal tube spaces of the nanotube. In addition, a decrease intensity of XRD pattern of Au@SWCNT at around 2θ ≈ 2.6° supports the suggestion that Au nanoparticles are really encapsulated into SWCNT.
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Wright, James L., and Steven R. Koehler. "North Bullion: Latest gold discovery on the Carlin Trend, Nevada." Interpretation 3, no. 2 (May 1, 2015): SL27—SL38. http://dx.doi.org/10.1190/int-2014-0187.1.
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Gold Standard Ventures Corp. highlighted in their 2014 corporate presentation that “North Bullion and Central Bullion were both gravity- and CSAMT-led discoveries.” The North Bullion gold discovery demonstrates the continued effectiveness of geophysics as applied to gold exploration on the Carlin Trend of northeast Nevada. In combination with geologic understanding and target model development, geophysics provides a cost-effective exploration tool to guide exploration drilling. A sustained, incremental program is critical to realizing the full benefit geophysics brings to the exploration effort. In a program spanning five years, 3587 gravity stations and 51.7 line-km of controlled-source audio magnetotelluric (CSAMT) data have been acquired in a multistage approach. A major structure, called the Bullion Fault Corridor (BFC), hosts two known gold deposits over an 18-km strike length. Gravity, followed up with CSAMT, defines the BFC in detail, as well as hydrothermal alteration products related to the mineralization process. Drill and geologic confirmation is integrated with the geophysics to refine interpretations and adjust ongoing survey design. Application of gravity along the Carlin Trend has been actively used as a structural mapping tool for many years. However, combining the results with CSAMT is a more recent development, particularly along the Carlin Trend.
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Martinez Espinosa, Juan Carlos, Miguel Jose Yacaman, German Plascencia Villa, Ana Karen Zavala Raya, Jacqueline Torres Ramirez, Ana Pamela Andrade Perez, and Teodoro Cordova Fraga. "Coating identification in spherical and anisotropic gold nanomaterials by SERS technique." MRS Advances 3, no. 41 (2018): 2461–65. http://dx.doi.org/10.1557/adv.2018.439.
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AbstractRecently the use of nanomaterials for the diagnosis and detection of malignant diseases has increased due to the versatility and properties of these nanostructures. For this work 60 nm commercial gold nanoparticles (TED PELLA inc.) and Nanostars manufactured by chemical synthesis (precursor reagent: HAuCl4, cationic surfactant: CTAB) of 117 nm were used for coating. Malachite green Isotyocianate (MGITC), mPEG-SH and ortho-pyridyldisulfide-polyethylene glycol-N-succinimidyl propionate (OPSS-PEG-NHS) was used. A SERS active nanoparticle complex was obtained by addition of a solution of MGITC to the gold nanoparticles colloidal solution in a 1:6 ratio. Later, an mPEG-SH solution was added to the mix. The nanoparticle-MGITC-mPEG-SH complex stability was revised using a UV-Vis spectrophotometer and a JEOL JEM 1000 transmission electron microscope. The SERS spectra were registered with a Raman Thermoscientific DXR microscopy system. Amplified bands associated with OPSS-PEG-NHS were identified in 389, 622, 859, 929, 1080, 1283, 1360, 1443, 1490 and 1450 cm-1. The results indicate that through this methodology it is possible to identify gold nanomaterials coated with polymer through the Raman technique. In addition, greater amplification is observed with the use of nanostars compared to gold spheres. Finally, these nanomaterials are available for the marking of specific membrane for the study of different types of cancer by the SERS technique.
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Nwanze, Julum, Cynthia Cohen, Alessandra C. Schmitt, and Momin T. Siddiqui. "β-Catenin Expression in Oropharyngeal Squamous Cell Carcinomas: Comparison and Correlation with p16 and Human Papillomavirus in situ Hybridization." Acta Cytologica 59, no. 6 (2015): 479–84. http://dx.doi.org/10.1159/000443602.
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Background: The Wnt/β-catenin signaling pathway has been noted to be upregulated in head and neck cancers, including oropharyngeal squamous cell carcinoma (OSCC). This study compared the efficacy of β-catenin immunohistochemistry (IHC), p16 IHC and automated human papillomavirus (HPV) in situ hybridization (ISH) in OSCC. Methods: Sixty-eight OSCCs (48 surgical specimens and 20 fine-needle aspirations) were evaluated. Nuclear staining only of β-catenin was assessed as 0-3+ intensity (relative to controls of benign squamous mucosa). p16 was interpreted as positive if 70% of tumor cells showed brown nuclear and cytoplasmic staining. HPV ISH was interpreted as positive if a minimum of one tumor cell showed brown punctate dot-like nuclear positivity. p16 IHC and HPV ISH were then correlated with β-catenin staining. HPV ISH was used as the gold standard. Results: Twenty-five of 48 surgical specimens (52.1%) and 11 of 20 cell blocks (55%) stained positively for β-catenin, making a total of 36 of 68 (52.9%) staining positively for β-catenin, as compared to 61.7% positive for p16 IHC and 70.6% positive by automated HPV ISH, the gold standard method for OSCC diagnosis. χ2 analysis revealed no significant correlation between β-catenin and HPV ISH (p > 0.05) and demonstrated a strong correlation between p16 and HPV ISH (p < 0.05). Conclusion: β-Catenin IHC is not a sensitive or specific marker of HPV and is unlikely to be a useful adjunct to p16 IHC or HPV ISH in the setting of advanced OSCC. However, as this study focused on samples of advanced OSCC, β-catenin IHC may still find some use in the diagnosis of early-stage OSCC.
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Hastuti, Sri, Nuryono Nuryono, and Agus Kuncaka. "L-Arginine-Modified Silica for Adsorption of Gold(III)." Indonesian Journal of Chemistry 15, no. 2 (July 13, 2015): 108–15. http://dx.doi.org/10.22146/ijc.21203.
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In this research, L-arginine-modified silica (SiO2-Arg) with 3-glycidoxypropyl-trimethoxysilane (GPTMS) as the linking agent has been synthesized through sol gel process for adsorption of Au(III) in aqueous solution. Tetraethyl orthosilicate (TEOS) as the silica source precursor, L-arginine solution 0.9 M with various volume ratios and the linking agent were mixed together to form a gel. SiO2-Arg was characterized using Fourier transform infrared (FTIR) spectrophotometer, thermogravimetric analysis (TGA), and an elemental analysis. Adsorption was carried out in a batch system under various experimental conditions including contact time and initial concentration of metal Au(III). The selectivity of adsorbent toward Au(III) was examined in the presence of Cu(II), Fe(III), and Zn(II) ion at various pHs. Results of characterization showed that silica has been successfully modified with L-arginine. The optimum adsorption of Au(III) on SiO2-Arg was obtained at pH of 3.0 and the adsorption isotherm of Au(III) on SiO2-Arg gives the adsorption capacity of 52.79 mg/g. The kinetic study demonstrates that the adsorption of Au(III) ion follows pseudo-second order with the rate constant of 53197 g mol–1 min–1. The selectivity order of Au-Zn = Au-Cu > Au-Fe. This sol-gel preparation is simple and provides prospective application of SiO2-Arg material as an effective adsorbent for metal ions particularly gold(III).