Showing papers by "New York University published in 2006"

Understanding Interaction Models: Improving Empirical Analyses

Abstract: Multiplicative interaction models are common in the quantitative political science literature. This is so for good reason. Institutional arguments frequently imply that the relationship between political inputs and outcomes varies depending on the institutional context. Models of strategic interaction typically produce conditional hypotheses as well. Although conditional hypotheses are ubiquitous in political science and multiplicative interaction models have been found to capture their intuition quite well, a survey of the top three political science journals from 1998 to 2002 suggests that the execution of these models is often flawed and inferential errors are common. We believe that considerable progress in our understanding of the political world can occur if scholars follow the simple checklist of dos and don'ts for using multiplicative interaction models presented in this article. Only 10% of the articles in our survey followed the checklist.

Reporting structural equation modeling and confirmatory factor analysis results: A review

Abstract: The authors provide a basic set of guidelines and recommendations for information that should be included in any manuscript that has confirmatory factor analysis or structural equation modeling as the primary statistical analysis technique. The authors provide an introduction to both techniques, along with sample analyses, recommendations for reporting, evaluation of articles in The Journal of Educational Research using these techniques, and concluding remarks.

Dimensionality Reduction by Learning an Invariant Mapping

Abstract: Dimensionality reduction involves mapping a set of high dimensional input points onto a low dimensional manifold so that 'similar" points in input space are mapped to nearby points on the manifold. We present a method - called Dimensionality Reduction by Learning an Invariant Mapping (DrLIM) - for learning a globally coherent nonlinear function that maps the data evenly to the output manifold. The learning relies solely on neighborhood relationships and does not require any distancemeasure in the input space. The method can learn mappings that are invariant to certain transformations of the inputs, as is demonstrated with a number of experiments. Comparisons are made to other techniques, in particular LLE.

Investor sentiment and the cross-section of stock returns

Abstract: We study how investor sentiment affects the cross-section of stock returns. We predict that a wave of investor sentiment has larger effects on securities whose valuations are highly subjective and difficult to arbitrage. Consistent with this prediction, we find that when beginning-of-period proxies for sentiment are low, subsequent returns are relatively high for small stocks, young stocks, high volatility stocks, unprofitable stocks, non-dividend-paying stocks, extreme growth stocks, and distressed stocks. When sentiment is high, on the other hand, these categories of stock earn relatively low subsequent returns.

Meeting of minds: the medial frontal cortex and social cognition.

Abstract: Social interaction is a cornerstone of human life, yet the neural mechanisms underlying social cognition are poorly understood. Recently, research that integrates approaches from neuroscience and social psychology has begun to shed light on these processes, and converging evidence from neuroimaging studies suggests a unique role for the medial frontal cortex. We review the emerging literature that relates social cognition to the medial frontal cortex and, on the basis of anatomical and functional characteristics of this brain region, propose a theoretical model of medial frontal cortical function relevant to different aspects of social cognitive processing.

Cryopyrin activates the inflammasome in response to toxins and ATP

Abstract: A crucial part of the innate immune response is the assembly of the inflammasome, a cytosolic complex of proteins that activates caspase-1 to process the proinflammatory cytokines interleukin (IL)-1beta and IL-18. The adaptor protein ASC is essential for inflammasome function, binding directly to caspase-1 (refs 3, 4), but the triggers of this interaction are less clear. ASC also interacts with the adaptor cryopyrin (also known as NALP3 or CIAS1). Activating mutations in cryopyrin are associated with familial cold autoinflammatory syndrome, Muckle-Wells syndrome and neonatal onset multisystem inflammatory disease, diseases that are characterized by excessive production of IL-1beta. Here we show that cryopyrin-deficient macrophages cannot activate caspase-1 in response to Toll-like receptor agonists plus ATP, the latter activating the P2X7 receptor to decrease intracellular K+ levels. The release of IL-1beta in response to nigericin, a potassium ionophore, and maitotoxin, a potent marine toxin, was also found to be dependent on cryopyrin. In contrast to Asc-/- macrophages, cells deficient in the gene encoding cryopyrin (Cias1-/-) activated caspase-1 and secreted normal levels of IL-1beta and IL-18 when infected with Gram-negative Salmonella typhimurium or Francisella tularensis. Macrophages exposed to Gram-positive Staphylococcus aureus or Listeria monocytogenes, however, required both ASC and cryopyrin to activate caspase-1 and secrete IL-1beta. Therefore, cryopyrin is essential for inflammasome activation in response to signalling pathways triggered specifically by ATP, nigericin, maitotoxin, S. aureus or L. monocytogenes.

The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America

Abstract: Evidence-based guidelines for the management of patients with Lyme disease, human granulocytic anaplasmosis (formerly known as human granulocytic ehrlichiosis), and babesiosis were prepared by an expert panel of the Infectious Diseases Society of America. These updated guidelines replace the previous treatment guidelines published in 2000 (Clin Infect Dis 2000; 31[Suppl 1]:1-14). The guidelines are intended for use by health care providers who care for patients who either have these infections or may be at risk for them. For each of these Ixodes tickborne infections, information is provided about prevention, epidemiology, clinical manifestations, diagnosis, and treatment. Tables list the doses and durations of antimicrobial therapy recommended for treatment and prevention of Lyme disease and provide a partial list of therapies to be avoided. A definition of post-Lyme disease syndrome is proposed.

Parents' ethnic-racial socialization practices: a review of research and directions for future study.

Abstract: Recently, there has been an emergence of literature on the mechanisms through which parents transmit information, values, and perspectives about ethnicity and race to their children, commonly referred to as racial or ethnic socialization. This literature has sought to document the nature of such socialization, its antecedents in parents' and children's characteristics and experiences, and its consequences for children's well-being and development. In this article, the authors integrate and synthesize what is known about racial and ethnic socialization on the basis of current empirical research, examining studies concerning its nature and frequency; its child, parent, and ecological predictors; and its consequences for children's development, including ethnic identity, self-esteem, coping with discrimination, academic achievement, and psychosocial well-being. The authors also discuss conceptual and methodological limitations of the literature and suggest directions for future research.

Asymmetric Dynamics in the Correlations of Global Equity and Bond Returns

Abstract: This paper proposes a new generalized autoregressive conditionally heteroskedastic (GARCH) process, the asymmetric generalized dynamic conditional correlation (AG-DCC) model The AG-DCC process extends previous specifications along two dimensions: it allows for series-specific news impact and smoothing parameters and permits conditional asymmetries in correlation dynamics The AG-DCC specification is well suited to examine correlation dynamics among different asset classes and investigate the presence of asymmetric responses in conditional variances and correlations to negative returns We employ the AG-DCC model to analyze the behavior of international equities and government bonds While equity returns show strong evidence of asymmetries in conditional volatility, little is found for bond returns However, both equities and bonds exhibit asymmetries in conditional correlations, with equities responding stronger than bonds to joint bad news The article also finds that, during periods of financial turmoil, equity market volatilities show important linkages, and conditional equity correlations among regional groups increase dramatically Furthermore, in January 1999 with the introduction of the euro, we document significant evidence of a structural break in correlation although not in

Psychological perspectives on legitimacy and legitimation.

Abstract: Legitimacy is a psychological property of an authority, institution, or social arrangement that leads those connected to it to believe that it is appropriate, proper, and just. Because of legitimacy, people feel that they ought to defer to decisions and rules, following them voluntarily out of obligation rather than out of fear of punishment or anticipation of reward. Being legitimate is important to the success of authorities, institutions, and institutional arrangements since it is difficult to exert influence over others based solely upon the possession and use of power. Being able to gain voluntary acquiescence from most people, most of the time, due to their sense of obligation increases effectiveness during periods of scarcity, crisis, and conflict. The concept of legitimacy has a long history within social thought and social psychology, and it has emerged as increasingly important within recent research on the dynamics of political, legal, and social systems.

Insights into social insects from the genome of the honeybee Apis mellifera

Abstract: Here we report the genome sequence of the honeybee Apis mellifera, a key model for social behaviour and essential to global ecology through pollination. Compared with other sequenced insect genomes, the A. mellifera genome has high A+T and CpG contents, lacks major transposon families, evolves more slowly, and is more similar to vertebrates for circadian rhythm, RNA interference and DNA methylation genes, among others. Furthermore, A. mellifera has fewer genes for innate immunity, detoxification enzymes, cuticle-forming proteins and gustatory receptors, more genes for odorant receptors, and novel genes for nectar and pollen utilization, consistent with its ecology and social organization. Compared to Drosophila, genes in early developmental pathways differ in Apis, whereas similarities exist for functions that differ markedly, such as sex determination, brain function and behaviour. Population genetics suggests a novel African origin for the species A. mellifera and insights into whether Africanized bees spread throughout the New World via hybridization or displacement.

Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome.

Abstract: Aortic aneurysm and dissection are manifestations of Marfan syndrome (MFS), a disorder caused by mutations in the gene that encodes fibrillin-1. Selected manifestations of MFS reflect excessive signaling by the transforming growth factor–β (TGF-β) family of cytokines. We show that aortic aneurysm in a mouse model of MFS is associated with increased TGF-β signaling and can be prevented by TGF-β antagonists such as TGF-β–neutralizing antibody or the angiotensin II type 1 receptor (AT1) blocker, losartan. AT1 antagonism also partially reversed noncardiovascular manifestations of MFS, including impaired alveolar septation. These data suggest that losartan, a drug already in clinical use for hypertension, merits investigation as a therapeutic strategy for patients with MFS and has the potential to prevent the major life-threatening manifestation of this disorder.

Sentinel-node biopsy or nodal observation in melanoma

Abstract: Among 1269 patients with an intermediate-thickness primary melanoma, the mean (±SE) estimated 5-year disease-free survival rate for the population was 78.3±1.6% in the biopsy group and 73.1±2.1% in the observation group (hazard ratio for death, 0.74; 95% confidence interval [CI], 0.59 to 0.93; P = 0.009). Five-year melanoma-specific survival rates were similar in the two groups (87.1±1.3% and 86.6±1.6%, respectively). In the biopsy group, the presence of metastases in the sentinel node was the most important prognostic factor; the 5-year survival rate was 72.3±4.6% among patients with tumor-positive sentinel nodes and 90.2±1.3% among those with tumor-negative sentinel nodes (hazard ratio for death, 2.48; 95% CI, 1.54 to 3.98; P<0.001). The incidence of sentinel-node micrometastases was 16.0% (122 of 764 patients), and the rate of nodal relapse in the observation group was 15.6% (78 of 500 patients). The corresponding mean number of tumor-involved nodes was 1.4 in the biopsy group and 3.3 in the observation group (P<0.001), indicating disease progression during observation. Among patients with nodal metastases, the 5-year survival rate was higher among those who underwent immediate lymphadenectomy than among those in whom lymphadenectomy was delayed (72.3±4.6% vs. 52.4±5.9%; hazard ratio for death, 0.51; 95% CI, 0.32 to 0.81; P = 0.004). Conclusions The staging of intermediate-thickness (1.2 to 3.5 mm) primary melanomas according to the results of sentinel-node biopsy provides important prognostic information and identifies patients with nodal metastases whose survival can be prolonged by immediate lymphadenectomy. (ClinicalTrials.gov number, NCT00275496.)

Cosmological constraints from the SDSS luminous red galaxies

Abstract: We measure the large-scale real-space power spectrum P(k) using luminous red galaxies (LRGs) in the Sloan Digital Sky Survey (SDSS) and use this measurement to sharpen constraints on cosmological parameters from the Wilkinson Microwave Anisotropy Probe (WMAP). We employ a matrix-based power spectrum estimation method using Pseudo-Karhunen-Loeve eigenmodes, producing uncorrelated minimum-variance measurements in 20 k-bands of both the clustering power and its anisotropy due to redshift-space distortions, with narrow and well-behaved window functions in the range 0.01h/Mpc 0.1h/Mpc and associated nonlinear complications, yet agree well with more aggressive published analyses where nonlinear modeling is crucial.

Hypoxia-inducible factor-1 (HIF-1).

Abstract: Adaptation to low oxygen tension (hypoxia) in cells and tissues leads to the transcriptional induction of a series of genes that participate in angiogenesis, iron metabolism, glucose metabolism, and cell proliferation/survival. The primary factor mediating this response is the hypoxia-inducible factor-1 (HIF-1), an oxygen-sensitive transcriptional activator. HIF-1 consists of a constitutively expressed subunit HIF-1β and an oxygen-regulated subunit HIF-1α (or its paralogs HIF-2α and HIF-3α). The stability and activity of the α subunit of HIF are regulated by its post-translational modifications such as hydroxylation, ubiquitination, acetylation, and phosphorylation. In normoxia, hydroxylation of two proline residues and acetylation of a lysine residue at the oxygen-dependent degradation domain (ODDD) of HIF-1α trigger its association with pVHL E3 ligase complex, leading to HIF-1α degradation via ubiquitin-proteasome pathway. In hypoxia, the HIF-1α subunit becomes stable and interacts with coactivators such as cAMP response element-binding protein binding protein/p300 and regulates the expression of target genes. Overexpression of HIF-1 has been found in various cancers, and targeting HIF-1 could represent a novel approach to cancer therapy.

Spatial Diversity in Radars&#8212;Models and Detection Performance

Abstract: Inspired by recent advances in multiple-input multiple-output (MIMO) communications, this proposal introduces the statistical MIMO radar concept To the authors' knowledge, this is the first time that the statistical MIMO is being proposed for radar The fundamental difference between statistical MIMO and other radar array systems is that the latter seek to maximize the coherent processing gain, while statistical MIMO radar capitalizes on the diversity of target scattering to improve radar performance Coherent processing is made possible by highly correlated signals at the receiver array, whereas in statistical MIMO radar, the signals received by the array elements are uncorrelated Radar targets generally consist of many small elemental scatterers that are fused by the radar waveform and the processing at the receiver, to result in echoes with fluctuating amplitude and phase It is well known that in conventional radar, slow fluctuations of the target radar cross section (RCS) result in target fades that degrade radar performance By spacing the antenna elements at the transmitter and at the receiver such that the target angular spread is manifested, the MIMO radar can exploit the spatial diversity of target scatterers opening the way to a variety of new techniques that can improve radar performance This paper focuses on the application of the target spatial diversity to improve detection performance The optimal detector in the Neyman–Pearson sense is developed and analyzed for the statistical MIMO radar It is shown that the optimal detector consists of noncoherent processing of the receiver sensors' outputs and that for cases of practical interest, detection performance is superior to that obtained through coherent processing An optimal detector invariant to the signal and noise levels is also developed and analyzed In this case as well, statistical MIMO radar provides great improvements over other types of array radars

Aneurysm Syndromes Caused by Mutations in the TGF-β Receptor

Abstract: Background The Loeys–Dietz syndrome is a recently described autosomal dominant aortic-aneurysm syndrome with widespread systemic involvement The disease is characterized by the triad of arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate and is caused by heterozygous mutations in the genes encoding transforming growth factor β receptors 1 and 2 (TGFBR1 and TGFBR2, respectively) Methods We undertook the clinical and molecular characterization of 52 affected families Forty probands presented with typical manifestations of the Loeys–Dietz syndrome In view of the phenotypic overlap between this syndrome and vascular Ehlers–Danlos syndrome, we screened an additional cohort of 40 patients who had vascular Ehlers–Danlos syndrome without the characteristic type III collagen abnormalities or the craniofacial features of the Loeys–Dietz syndrome Results We found a mutation in TGFBR1 or TGFBR2 in all probands with typical Loeys–Dietz syndrome (type I) and in 12 probands presenting

Examining the Relationship Between Reviews and Sales: The Role of Reviewer Identity Disclosure in Electronic Markets

Abstract: Consumer-generated product reviews have proliferated online, driven by the notion that consumers' decision to purchase or not purchase a product is based on the positive or negative information about that product they obtain from fellow consumers. Using research on information processing (Chaiken 1980) as a foundation, we suggest that in the context of an online community, reviewer disclosure of identity-descriptive information is used by consumers to supplement or replace product information when making purchase decisions and evaluating the helpfulness of online reviews. Using a unique dataset based on both chronologically compiled ratings as well as reviewer characteristics for a given set of products and geographical location-based purchasing behavior from Amazon, we provide evidence that community norms are an antecedent to reviewer disclosure of identity-descriptive information. Amazon members rate reviews containing identity-descriptive information more positively, and the prevalence of reviewer disclosure of identity information is associated with increases in subsequent online product sales. In addition, we show that when reviewers are from a particular geographic location, subsequent product sales are higher in that region, thus highlighting the important role of geography in electronic commerce. Taken together, our results suggest that identity-relevant information about reviewers shapes community members' judgment of products and reviews. Implications for research on the relationship between online reviews and sales, peer recognition systems, and conformity to online community norms are discussed.

Bivalirudin for Patients with Acute Coronary Syndromes

Abstract: Bivalirudin plus a glycoprotein IIb/IIIa inhibitor, as compared with heparin plus a glycoprotein IIb/IIIa inhibitor, was associated with noninferior 30-day rates of the composite ischemia end point (7.7% and 7.3%, respectively), major bleeding (5.3% and 5.7%), and the net clinical outcome end point (11.8% and 11.7%). Bivalirudin alone, as compared with heparin plus a glycoprotein IIb/IIIa inhibitor, was associated with a noninferior rate of the composite ischemia end point (7.8% and 7.3%, respectively; P = 0.32; relative risk, 1.08; 95% confidence interval [CI], 0.93 to 1.24) and significantly reduced rates of major bleeding (3.0% vs. 5.7%; P<0.001; relative risk, 0.53; 95% CI, 0.43 to 0.65) and the net clinical outcome end point (10.1% vs. 11.7%; P = 0.02; relative risk, 0.86; 95% CI, 0.77 to 0.97). Conclusions In patients with moderate- or high-risk acute coronary syndromes who were undergoing invasive treatment with glycoprotein IIb/IIIa inhibitors, bivalirudin was associated with rates of ischemia and bleeding that were similar to those with heparin. Bivalirudin alone was associated with similar rates of ischemia and significantly lower rates of bleeding. (ClinicalTrials.gov number, NCT00093158.)

Control of microglial neurotoxicity by the fractalkine receptor

Abstract: Microglia, the resident inflammatory cells of the CNS, are the only CNS cells that express the fractalkine receptor (CX3CR1). Using three different in vivo models, we show that CX3CR1 deficiency dysregulates microglial responses, resulting in neurotoxicity. Following peripheral lipopolysaccharide injections, Cx3cr1−/− mice showed cell-autonomous microglial neurotoxicity. In a toxic model of Parkinson disease and a transgenic model of amyotrophic lateral sclerosis, Cx3cr1−/− mice showed more extensive neuronal cell loss than Cx3cr1+ littermate controls. Augmenting CX3CR1 signaling may protect against microglial neurotoxicity, whereas CNS penetration by pharmaceutical CX3CR1 antagonists could increase neuronal vulnerability.

Emotion and Cognition: Insights from Studies of the Human Amygdala

Abstract: Traditional approaches to the study of cognition emphasize an information-processing view that has generally excluded emotion. In contrast, the recent emergence of cognitive neuroscience as an inspiration for understanding human cognition has highlighted its interaction with emotion. This review explores insights into the relations between emotion and cognition that have resulted from studies of the human amygdala. Five topics are explored: emotional learning, emotion and memory, emotion's influence on attention and perception, processing emotion in social stimuli, and changing emotional responses. Investigations into the neural systems underlying human behavior demonstrate that the mechanisms of emotion and cognition are intertwined from early perception to reasoning. These findings suggest that the classic division between the study of emotion and cognition may be unrealistic and that an understanding of human cognition requires the consideration of emotion.

Gr-1+CD115+ Immature Myeloid Suppressor Cells Mediate the Development of Tumor-Induced T Regulatory Cells and T-Cell Anergy in Tumor-Bearing Host

Abstract: The accumulation of myeloid suppressor cells (MSCs) is associated with immune suppression in tumor-bearing mice and in cancer patients. The suppressive activity of MSC correlates with the expression of the myeloid markers Gr-1, CD115 (macrophage colony-stimulating factor receptor), and F4/80. Gr-1 + CD115 + MSCs, in addition to being able to suppress T-cell proliferation in vitro , can induce the development of Foxp3 + T regulatory cells (Treg) in vivo , which are anergic and suppressive. Furthermore, the secretion of interleukin (IL)-10 and transforming growth factor-β by Gr-1 + CD115 + MSCs was induced and enhanced, respectively, on IFN-γ stimulation. The development of Treg requires antigen-associated activation of tumor-specific T cells, depends on the presence of IFN-γ and IL-10, and is independent of the nitric oxide–mediated suppressive mechanism by MSC. Our data provide evidence that Gr-1 + CD115 + MSC can mediate the development of Treg in tumor-bearing mice and show a novel immune suppressive mechanism by which MSCs can suppress antitumor responses. (Cancer Res 2006; 66(2): 1123-31)

BRAF mutation predicts sensitivity to MEK inhibition

Abstract: The kinase pathway comprising RAS, RAF, mitogen-activated protein kinase kinase (MEK) and extracellular signal regulated kinase (ERK) is activated in most human tumours, often through gain-of-function mutations of RAS and RAF family members. Using small-molecule inhibitors of MEK and an integrated genetic and pharmacologic analysis, we find that mutation of BRAF is associated with enhanced and selective sensitivity to MEK inhibition when compared to either 'wild-type' cells or cells harbouring a RAS mutation. This MEK dependency was observed in BRAF mutant cells regardless of tissue lineage, and correlated with both downregulation of cyclin D1 protein expression and the induction of G1 arrest. Pharmacological MEK inhibition completely abrogated tumour growth in BRAF mutant xenografts, whereas RAS mutant tumours were only partially inhibited. These data suggest an exquisite dependency on MEK activity in BRAF mutant tumours, and offer a rational therapeutic strategy for this genetically defined tumour subtype.

Party Policy in Modern Democracies

Abstract: Introduction Part I. Policy and Party Competition 1. Policy dimensions and political preferences 2. "Policy spaces" and models of party competition Part II. Measuring Policy Positions 3. The expert surveys as a measurement tool 4. Measurement issues: bias and error correction in expert survey results 5. The Dimensionality of policy spaces 6. Comparing patterns of party competition Part III. Data Appendices References Index

A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development

Abstract: The chemokine stromal cell–derived factor (SDF-1; also known as chemokine ligand 12 [CXCL12]) regulates many essential biological processes, including cardiac and neuronal development, stem cell motility, neovascularization, angiogenesis, apoptosis, and tumorigenesis. It is generally believed that SDF-1 mediates these many disparate processes via a single cell surface receptor known as chemokine receptor 4 (CXCR4). This paper characterizes an alternate receptor, CXCR7, which binds with high affinity to SDF-1 and to a second chemokine, interferon-inducible T cell α chemoattractant (I-TAC; also known as CXCL11). Membrane-associated CXCR7 is expressed on many tumor cell lines, on activated endothelial cells, and on fetal liver cells, but on few other cell types. Unlike many other chemokine receptors, ligand activation of CXCR7 does not cause Ca2+ mobilization or cell migration. However, expression of CXCR7 provides cells with a growth and survival advantage and increased adhesion properties. Consistent with a role for CXCR7 in cell survival and adhesion, a specific, high affinity small molecule antagonist to CXCR7 impedes in vivo tumor growth in animal models, validating this new receptor as a target for development of novel cancer therapeutics.

Efficient Learning of Sparse Representations with an Energy-Based Model

Abstract: We describe a novel unsupervised method for learning sparse, overcomplete features. The model uses a linear encoder, and a linear decoder preceded by a sparsifying non-linearity that turns a code vector into a quasi-binary sparse code vector. Given an input, the optimal code minimizes the distance between the output of the decoder and the input patch while being as similar as possible to the encoder output. Learning proceeds in a two-phase EM-like fashion: (1) compute the minimum-energy code vector, (2) adjust the parameters of the encoder and decoder so as to decrease the energy. The model produces "stroke detectors" when trained on handwritten numerals, and Gabor-like filters when trained on natural image patches. Inference and learning are very fast, requiring no preprocessing, and no expensive sampling. Using the proposed unsupervised method to initialize the first layer of a convolutional network, we achieved an error rate slightly lower than the best reported result on the MNIST dataset. Finally, an extension of the method is described to learn topographical filter maps.

Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis

Abstract: Background Glucosamine and chondroitin sulfate are used to treat osteoarthritis. The multicenter, double-blind, placebo- and celecoxib-controlled Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) evaluated their efficacy and safety as a treatment for knee pain from osteoarthritis. Methods We randomly assigned 1583 patients with symptomatic knee osteoarthritis to receive 1500 mg of glucosamine daily, 1200 mg of chondroitin sulfate daily, both glucosamine and chondroitin sulfate, 200 mg of celecoxib daily, or placebo for 24 weeks. Up to 4000 mg of acetaminophen daily was allowed as rescue analgesia. Assignment was stratified according to the severity of knee pain (mild [N=1229] vs. moderate to severe [N=354]). The primary outcome measure was a 20 percent decrease in knee pain from baseline to week 24. Results The mean age of the patients was 59 years, and 64 percent were women. Overall, glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20 perce...