Institution
Novartis
Company•Basel, Switzerland•
About: Novartis is a company organization based out in Basel, Switzerland. It is known for research contribution in the topics: Alkyl & Population. The organization has 41930 authors who have published 50566 publications receiving 1978996 citations. The organization is also known as: Novartis International AG.
Topics: Alkyl, Population, Alkoxy group, Tolerability, Receptor
Papers published on a yearly basis
Papers
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TL;DR: With prolonged follow-up, treatment with high-dose recombinant IL-2 remains extremely effective for a subset of patients with metastatic renal cell carcinoma.
Abstract: Purpose To update response duration and survival data for patients with metastatic renal cell carcinoma treated with high-dose interleukin (IL)-2 Patients and methods Two hundred fifty-five assessable patients were entered onto seven phase II clinical trials Recombinant IL-2 600,000 or 720,000 IU/kg was administered by 15-minute intravenous infusion every 8 hours for up to 14 consecutive doses over 5 days as clinically tolerated with maximal support A second, identical cycle of treatment was scheduled following 5 to 9 days of rest, and courses could be repeated every 6 to 12 weeks in stable or responding patients All data were updated as of December 1998, with report forms completed by the clinical investigators These data had last been updated as part of the Food and Drug Administration reporting requirements in 1996 Results Objective responses previously have been reported in 37 of 255 patients (15%) with 17 complete responses (7%) and 20 partial responses (8%) These data remain unchanged from previous reports Median response duration for all objective responders remains unchanged at 54 months, but the range now extends from 3 to > 131 months Median duration for all complete responses has not yet been reached, but was at least 80 months (range, 7- > 131 mo) at the time of this analysis Median duration for all partial responses remains 20 months (range, 3- > 126 mo) Median survival time for all 255 patients remains 163 months, with 10% to 20% of patients estimated to be alive 5 to 10 years after treatment with high-dose IL-2 Conclusion With prolonged follow-up, treatment with high-dose recombinant IL-2 remains extremely effective for a subset of patients with metastatic renal cell carcinoma
436 citations
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TL;DR: The combination of aliskiren and valsartan at maximum recommended doses provides significantly greater reductions in blood pressure than does monotherapy with either agent in patients with hypertension, with a tolerability profile similar to that with aliskirens and valartan alone.
435 citations
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TL;DR: The results demonstrate that the MAP kinase signaling pathway can discriminate between different MEF2 isoforms and can regulate MEF 2-dependent genes through posttranslational activation of preexisting MEf2 protein.
Abstract: Members of the MEF2 family of transcription factors bind as homo- and heterodimers to the MEF2 site found in the promoter regions of numerous muscle-specific, growth- or stress-induced genes. We showed previously that the transactivation activity of MEF2C is stimulated by p38 mitogen-activated protein (MAP) kinase. In this study, we examined the potential role of the p38 MAP kinase pathway in regulating the other MEF2 family members. We found that MEF2A, but not MEF2B or MEF2D, is a substrate for p38. Among the four p38 group members, p38 is the most potent kinase for MEF2A. Threonines 312 and 319 within the transcription activation domain of MEF2A are the regulatory sites phosphorylated by p38. Phosphorylation of MEF2A in a MEF2A-MEF2D heterodimer enhances MEF2-dependent gene expression. These results demonstrate that the MAP kinase signaling pathway can discriminate between different MEF2 isoforms and can regulate MEF2-dependent genes through posttranslational activation of preexisting MEF2 protein.
434 citations
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TL;DR: Canakinumab had modest but nonsignificant effects on the change in hemoglobin A1c, glucose, and insulin levels compared with placebo, and no effects were seen for low-density lipoprotein cholesterol, high-density LDL cholesterol, or non-high-density cholesterol, although triglyceride levels increased ≈10% in the 50-mg and 150-mg groups as discussed by the authors.
Abstract: Background—To test formally the inflammatory hypothesis of atherothrombosis, an agent is needed that reduces inflammatory biomarkers such as C-reactive protein, interleukin-6, and fibrinogen but that does not have major effects on lipid pathways associated with disease progression. Methods and Results—We conducted a double-blind, multinational phase IIb trial of 556 men and women with well-controlled diabetes mellitus and high cardiovascular risk who were randomly allocated to subcutaneous placebo or to subcutaneous canakinumab at doses of 5, 15, 50, or 150 mg monthly and followed over 4 months. Compared with placebo, canakinumab had modest but nonsignificant effects on the change in hemoglobin A1c, glucose, and insulin levels. No effects were seen for low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or non–high-density lipoprotein cholesterol, although triglyceride levels increased ≈10% in the 50-mg (P=0.02) and 150-mg (P=0.03) groups. By contrast, the median reductions in C-rea...
434 citations
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TL;DR: The positivity assumption is discussed in the context of assessing model and parameter-specific identifiability of causal effects and several approaches for improving the identifiable of parameters in the presence of positivity violations are reviewed.
Abstract: The assumption of positivity or experimental treatment assignment requires that observed treatment levels vary within confounder strata. This article discusses the positivity assumption in the context of assessing model and parameter-specific identifiability of causal effects. Positivity violations occur when certain subgroups in a sample rarely or never receive some treatments of interest. The resulting sparsity in the data may increase bias with or without an increase in variance and can threaten valid inference. The parametric bootstrap is presented as a tool to assess the severity of such threats and its utility as a diagnostic is explored using simulated and real data. Several approaches for improving the identifiability of parameters in the presence of positivity violations are reviewed. Potential responses to data sparsity include restriction of the covariate adjustment set, use of an alternative projection function to define the target parameter within a marginal structural working model, restriction of the sample, and modification of the target intervention. All of these approaches can be understood as trading off proximity to the initial target of inference for identifiability; we advocate approaching this tradeoff systematically.
434 citations
Authors
Showing all 41972 results
Name | H-index | Papers | Citations |
---|---|---|---|
Irving L. Weissman | 201 | 1141 | 172504 |
Peter J. Barnes | 194 | 1530 | 166618 |
Paul G. Richardson | 183 | 1533 | 155912 |
Kenneth C. Anderson | 178 | 1138 | 126072 |
Jie Zhang | 178 | 4857 | 221720 |
Lei Jiang | 170 | 2244 | 135205 |
Marc A. Pfeffer | 166 | 765 | 133043 |
Jorge E. Cortes | 163 | 2784 | 124154 |
Ian A. Wilson | 158 | 971 | 98221 |
Peter G. Schultz | 156 | 893 | 89716 |
Bruce D. Walker | 155 | 779 | 86020 |
Timothy P. Hughes | 145 | 831 | 91357 |
Kurt Wüthrich | 143 | 739 | 103253 |
Leonard Guarente | 143 | 352 | 80169 |
Christopher D.M. Fletcher | 138 | 674 | 82484 |