Institution
University of Wisconsin-Madison
Education•Madison, Wisconsin, United States•
About: University of Wisconsin-Madison is a education organization based out in Madison, Wisconsin, United States. It is known for research contribution in the topics: Population & Gene. The organization has 108707 authors who have published 237594 publications receiving 11883575 citations.
Topics: Population, Gene, Context (language use), Health care, Poison control
Papers published on a yearly basis
Papers
More filters
••
TL;DR: Addition of lutein + zeaxanthin, DHA + EPA, or both to the AREDS formulation in primary analyses did not reduce risk of progression to advanced AMD, but because of potential increased incidence of lung cancer in former smokers, luteIn + zexanthin could be an appropriate carotenoid substitute in the ARedS formulation.
Abstract: IMPORTANCE
Oral supplementation with the Age-Related Eye Disease Study (AREDS) formulation (antioxidant vitamins C and E, beta carotene, and zinc) has been shown to reduce the risk of progression to advanced age-related macular degeneration (AMD). Observational data suggest that increased dietary intake of lutein + zeaxanthin (carotenoids), omega-3 long-chain polyunsaturated fatty acids (docosahexaenoic acid [DHA] + eicosapentaenoic acid [EPA]), or both might further reduce this risk.
OBJECTIVES
To determine whether adding lutein + zeaxanthin, DHA + EPA, or both to the AREDS formulation decreases the risk of developing advanced AMD and to evaluate the effect of eliminating beta carotene, lowering zinc doses, or both in the AREDS formulation.
DESIGN, SETTING, AND PARTICIPANTS
The Age-Related Eye Disease Study 2 (AREDS2), a multicenter, randomized, double-masked, placebo-controlled phase 3 study with a 2 × 2 factorial design, conducted in 2006-2012 and enrolling 4203 participants aged 50 to 85 years at risk for progression to advanced AMD with bilateral large drusen or large drusen in 1 eye and advanced AMD in the fellow eye.
INTERVENTIONS
Participants were randomized to receive lutein (10 mg) + zeaxanthin (2 mg), DHA (350 mg) + EPA (650 mg), lutein + zeaxanthin and DHA + EPA, or placebo. All participants were also asked to take the original AREDS formulation or accept a secondary randomization to 4 variations of the AREDS formulation, including elimination of beta carotene, lowering of zinc dose, or both.
MAIN OUTCOMES AND MEASURES
Development of advanced AMD. The unit of analyses used was by eye.
RESULTS
Median follow-up was 5 years, with 1940 study eyes (1608 participants) progressing to advanced AMD. Kaplan-Meier probabilities of progression to advanced AMD by 5 years were 31% (493 eyes [406 participants]) for placebo, 29% (468 eyes [399 participants]) for lutein + zeaxanthin, 31% (507 eyes [416 participants]) for DHA + EPA, and 30% (472 eyes [387 participants]) for lutein + zeaxanthin and DHA + EPA. Comparison with placebo in the primary analyses demonstrated no statistically significant reduction in progression to advanced AMD (hazard ratio [HR], 0.90 [98.7% CI, 0.76-1.07]; P = .12 for lutein + zeaxanthin; 0.97 [98.7% CI, 0.82-1.16]; P = .70 for DHA + EPA; 0.89 [98.7% CI, 0.75-1.06]; P = .10 for lutein + zeaxanthin and DHA + EPA). There was no apparent effect of beta carotene elimination or lower-dose zinc on progression to advanced AMD. More lung cancers were noted in the beta carotene vs no beta carotene group (23 [2.0%] vs 11 [0.9%], nominal P = .04), mostly in former smokers.
CONCLUSIONS AND RELEVANCE
Addition of lutein + zeaxanthin, DHA + EPA, or both to the AREDS formulation in primary analyses did not further reduce risk of progression to advanced AMD. However, because of potential increased incidence of lung cancer in former smokers, lutein + zeaxanthin could be an appropriate carotenoid substitute in the AREDS formulation.
TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT00345176.
1,011 citations
••
TL;DR: A systematic examination of general three-dimensional autonomous ODE with quadratic nonlinearities has uncovered 19 distinct simple examples of chaotic flows with either five terms and two non-linearities or six terms and one nonlinearity as mentioned in this paper.
Abstract: A systematic examination of general three-dimensional autonomous ordinary differential equations with quadratic nonlinearities has uncovered 19 distinct simple examples of chaotic flows with either five terms and two nonlinearities or six terms and one nonlinearity. The properties of these systems are described, including their critical points, Lyapunov exponents, and fractal dimensions.
1,011 citations
••
TL;DR: This research aims to provide real-time information about how to improve the quality of life for people with learning disabilities and to provide a roadmap for the sustained support of those with learning difficulties.
Abstract: Carol Mitchell, PhD, ACS, RDMS, RDCS, RVT, RT(R), FASE, Co-Chair, Peter S. Rahko, MD, FASE, Co-Chair, Lori A. Blauwet, MD, FASE, Barry Canaday, RN, MS, RDCS, RCS, FASE, Joshua A. Finstuen, MA, RT(R), RDCS, FASE, Michael C. Foster, BA, RCS, RCCS, RDCS, FASE, Kenneth Horton, ACS, RCS, FASE, Kofo O. Ogunyankin, MD, FASE, Richard A. Palma, BS, RDCS, RCS, ACS, FASE, and Eric J. Velazquez, MD, FASE,Madison, Wisconsin; Rochester, Minnesota; Klamath Falls, Oregon; Durham, North Carolina; Salt Lake City, Utah; Ikoyi, Lagos, Nigeria; and Hartford, Connecticut
1,011 citations
••
TL;DR: Enantioselective PdII-catalyzed functionalization of alkenes has experienced considerably less success than have many other classes of enantiOSElective transformations, despite the extensive history of the Wacker process and related oxidation reactions.
Abstract: The development of catalytic reactions of alkenes transformed the chemical industry in the mid-20th century. Representative reactions included hydrogenation, oxidation, hydroformylation, oligomerization and polymerization. In 1959, researchers at Wacker Chemie developed a Pd-catalyzed method for the aerobic oxidative coupling of ethylene and water to produce acetaldehyde (eq 1, Scheme 1).1,2,3 This reaction represented the starting point for the development of numerous other Pd-catalyzed reactions in subsequent decades, ranging from alkene and diene oxidation reactions to cross-coupling reactions of aryl halides.
(1)
Scheme 1
The Wacker Reaction.
The stoichiometric oxidation of ethylene by aqueous PdII salts had been known since the 19th century;4 however, the industrial Wacker Process owes its success to the recognition that the oxidized catalyst could be regenerated by molecular oxygen in the presence of cocatalytic CuCl2 (Scheme 1). The reaction proceeds through a β-hydroxyethyl-PdII intermediate that forms via the net addition of hydroxide and Pd across the C–C double bond of ethylene. This seemingly straightforward “hydroxypalladation” step has been the subject of extensive mechanistic research and controversy over the past five decades. A major focus of this debate has centered on whether the reaction proceeds by a cis-hydroxypalladation pathway, involving migration of a coordinated water or hydroxide to the ethylene molecule (eq 2), or a trans-hydroxypalladation pathway, involving nucleophilic attack of exogenous water or hydroxide on the coordinated ethylene molecule (eq 3). The current mechanistic understanding of the hydroxypalladation step in the Wacker Process is the subject of an excellent recent review by Keith and Henry.3
(2)
(3)
Soon after the discovery of the Wacker process, a number of research groups demonstrated that PdII could facilitate the addition of several different nucleophiles to alkenes, and a variety of oxidative and non-oxidative C–O, C–N, and C–C bond-forming transformations have been developed, including intra- and intermolecular reactions.5 The PdII-alkyl intermediate formed in the nucleopalladation step can participate in a number of subsequent transformations (e.g., see Scheme 2). Such opportunities, together with the broad functional-group compatibility and air- and moisture-tolerance of the PdII-catalysts, enable the preparation of important organic building blocks as well as useful hetero- and carbocyclic molecules.
Scheme 2
Versatility of the PdII-Alkyl Intermediate Arising from Alkene Nucleopalladation.
Nucleopalladation of an alkene often generates a new stereogenic center, and the synthetic utility of the catalytic reactions is enhanced significantly if the stereochemical course of C–Nu bond formation can be controlled. Enantioselective PdII-catalyzed functionalization of alkenes has experienced considerably less success than have many other classes of enantioselective transformations, despite the extensive history of the Wacker process and related oxidation reactions. The former reactions face several challenges. Phosphine ligands, which have been highly successful in other enantioselective processes, are often incompatible with the oxidants used in these reactions (such as O2), and their σ-donating ability can attenuate the electrophilicity and/or oxidizing ability of the PdII salts. A mechanistic basis for the difficulty in achieving effective enantioselective catalysis is that nucleopalladation reactions are capable of proceeding by two stereochemically different pathways: cis- or trans-nucleopalladation (Scheme 3). Experimental results obtained over the past 40 years, especially in the last decade, demonstrate that the energy barriers associated with these different pathways can be very similar, in some cases similar enough that both pathways operate in parallel. This mechanistic scenario can increase the difficulty of achieving high levels of enantioinduction.
Scheme 3
Stereochemical Pathways of Nucleopalladation.
In the present review, we summarize recent progress in two synergistic areas: (1) mechanistic studies of the stereochemical pathway of nucleopalladation reactions of alkenes (i.e., cis- vs. trans-nucleopalladation) under catalytically relevant reaction conditions and (2) advances in the development of enantioselective Pd-catalyzed reactions that proceed via nucleopalladation of an alkene substrate. The results summarized in the first portion of this review highlight the mechanistic complexity of these reactions and illustrate how subtle changes to the catalyst, substrate, and/or the reaction conditions can alter the stereochemical course of the reaction. Despite the challenges associated with enantioselective PdII-catalyzed reactions of alkenes, important progress has been made over the past 10–15 years. These advances are surveyed in the second portion of this review. The comprehensive coverage of this review begins with results from the late 1990s and early 2000s, when several important advances were made, including the first examples of highly enantioselective reactions proceeding via nucleopalladation6,7,8,9 and the development of ligand-supported Pd-catalysts for aerobic Wacker-type cyclization reactions.10,11 It is hoped that the collective presentation of mechanistic insights and empirical reaction-discovery efforts in this review will provide a foundation for accelerated progress in this important field.
1,009 citations
••
TL;DR: Important biological and pharmacological disparities in pre-clinical research and human translational studies are highlighted, and analyses of clinical trial failures and recent successes provide a rational pathway to MSC regulatory approval and deployment for disorders with unmet medical needs.
1,009 citations
Authors
Showing all 109671 results
Name | H-index | Papers | Citations |
---|---|---|---|
Eric S. Lander | 301 | 826 | 525976 |
Ronald C. Kessler | 274 | 1332 | 328983 |
Gordon H. Guyatt | 231 | 1620 | 228631 |
Yi Chen | 217 | 4342 | 293080 |
David Miller | 203 | 2573 | 204840 |
Robert M. Califf | 196 | 1561 | 167961 |
Ronald Klein | 194 | 1305 | 149140 |
Joan Massagué | 189 | 408 | 149951 |
Jens K. Nørskov | 184 | 706 | 146151 |
Terrie E. Moffitt | 182 | 594 | 150609 |
H. S. Chen | 179 | 2401 | 178529 |
Ramachandran S. Vasan | 172 | 1100 | 138108 |
Masayuki Yamamoto | 171 | 1576 | 123028 |
Avshalom Caspi | 170 | 524 | 113583 |
Jiawei Han | 168 | 1233 | 143427 |