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Institution

Research Triangle Park

NonprofitDurham, North Carolina, United States
About: Research Triangle Park is a nonprofit organization based out in Durham, North Carolina, United States. It is known for research contribution in the topics: Population & Receptor. The organization has 24961 authors who have published 35800 publications receiving 1684504 citations. The organization is also known as: RTP.


Papers
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Journal ArticleDOI
TL;DR: The objective is to evaluate the efficacy and safety of lacosamide as adjunctive treatment in patients with uncontrolled partial‐onset seizures taking one to three concomitant antiepileptic drugs (AEDs).
Abstract: Purpose To evaluate the efficacy and safety of lacosamide (400 and 600 mg/day) as adjunctive treatment in patients with uncontrolled partial-onset seizures taking one to three concomitant antiepileptic drugs (AEDs). Methods This multicenter, double-blind, placebo-controlled trial randomized patients 1:2:1 to placebo, lacosamide 400 mg, or lacosamide 600 mg/day. After an 8-week baseline period, patients began treatment with placebo or lacosamide 100 mg/day, were force-titrated weekly (100 mg/day increments) to the target dose, and entered a 12-week maintenance period. Results A total of 405 patients were randomized and received trial medication. Most (82.1%) were taking two to three concomitant AEDs. Median percent reductions in seizure frequency per 28 days from baseline to maintenance (intention-to-treat, ITT) were 37.3% for lacosamide 400 mg/day (p = 0.008) and 37.8% for lacosamide 600 mg/day (p = 0.006) compared to 20.8% for placebo, with responder rates of 38.3% and 41.2%, respectively, compared to placebo (18.3%, p Discussion Adjunctive treatment with lacosamide 400 and 600 mg/day reduced seizure frequency for patients with uncontrolled partial-onset seizures. Lacosamide 400 mg/day provided a good balance of efficacy and tolerability; lacosamide 600 mg/day may provide additional benefit for some patients as suggested by secondary efficacy analyses, including response in patients with secondarily generalized tonic-clonic seizures.

286 citations

Journal ArticleDOI
TL;DR: These studies suggest that the biocontrol activity of bacteria can be dramatically increased to rival the activity of commercial chemical fungicides through directed genetic modification.
Abstract: It is now well established that some bacteria and fungi are aggressive colonizers of soil and the roots of plants, and are able to protect plants from infection by soil-borne fungal pathogens. In most cases that have been well studied, the biological mechanisms underlying this phenomenon, known as biocontrol, include the production of antifungal compounds, involving both metabolites and enzymes. Bacteria of the genus Pseudomonas comprise a large group of the active biocontrol strains as a result of their general ability to produce a diverse array of potent antifungal metabolites. These include simple metabolites such as 2,4-diacetylphloroglucinol, phenazine-1-carboxylic acid and pyrrolnitrin [3-chloro-4-(2'- nitro-3'-chlorophenyl)-pyrrole], as well as the complex macrocyclic lactone, 2,3-de-epoxy-2,3-didehydro-rhizoxin. Study of the biochemistry and mechanism of formation of these metabolites has proved useful in several ways. Pyrrolnitrin is active against Rhizoctonia spp, Fusarium spp, and other plant pathogenic fungi, and it has been used as a lead structure in the development of a new phenylpyrrole agricultural fungicide. In addition, pyrrolnitrin has been used for years as a model for the study of the mechanisms involved in the chlorination of organic molecules. We have cloned a four-gene cluster from a P fluorescens biocontrol strain that encodes the enzymes required for the production of pyrrolnitrin. Using these genes and strains mutated in the individual genes, we have elucidated the biochemical pathway by which pyrrolnitrin is synthesized. Studies of the genes involved in pyrrolnitrin biosynthesis have demonstrated that a new class of halogenase enzyme is involved in the chlorination reactions in pyrrolnitrin biosynthesis. The P fluorescens mutants that do not produce pyrrolnitrin have been used to demonstrate clearly the important role of pyrrolnitrin in the overall biocontrol activity shown by the strain. In addition, we have modified the pyrrolnitrin genes within the P fluorescens strain, which has resulted in significant increases in the production of this metabolite. The strains which overproduce pyrrolnitrin are also significantly more active than the wild-type strain in biocontrol. These studies suggest that the biocontrol activity of bacteria can be dramatically increased to rival the activity of commercial chemical fungicides through directed genetic modification. Bacteria remain important sources of natural products with diverse activities. In order to capture the full potential of these compounds, it will be necessary in the future to take a multidisciplinary approach to their study and development.

286 citations

Journal ArticleDOI
TL;DR: In this paper, the authors reviewed the recent literature on the relationship between obesity and indirect (non-medical) costs, including absenteeism, disability, premature mortality, presenteeism, workers' compensation, and total indirect costs.
Abstract: This study reviews the recent literature on the relationship between obesity and indirect (non-medical) costs. Medline and Web of Science searches were conducted to identify published studies from 1992 to present that report indirect costs by obesity status; 31 studies were included. The indirect costs were grouped into six categories: costs associated with absenteeism, disability, premature mortality, presenteeism, workers' compensation, and total indirect costs. Compared with non-obese workers, obese workers miss more workdays due to illness, injury, or disability. Costs of premature mortality vary substantially across countries. The results for presenteeism and workers' compensation were mixed. More research is needed to determine obesity's causal role in increasing indirect costs, especially for workers' compensation and presenteeism. Cohort and longitudinal study designs should be a priority.

286 citations

Journal ArticleDOI
TL;DR: Individuals with the GSTT1 null genotype may have enhanced susceptibility to MDS, and the mechanism might involve decreased detoxification of environmental or endogenous carcinogens.

285 citations

Journal ArticleDOI
TL;DR: The built environment and socioecologic characteristics of financially disadvantaged women were associated with BMI and CHD risk and the effects of racial segregation or acculturation on health for specific subpopulations are needed.

285 citations


Authors

Showing all 25006 results

NameH-indexPapersCitations
Douglas G. Altman2531001680344
Lewis C. Cantley196748169037
Ronald Klein1941305149140
Daniel J. Jacob16265676530
Christopher P. Cannon1511118108906
James B. Meigs147574115899
Lawrence Corey14677378105
Jeremy K. Nicholson14177380275
Paul M. Matthews14061788802
Herbert Y. Meltzer137114881371
Charles J. Yeo13667276424
Benjamin F. Cravatt13166661932
Timothy R. Billiar13183866133
Peter Brown12990868853
King K. Holmes12460656192
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202317
202277
2021988
20201,001
20191,035
20181,051