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Showing papers by "Yale University published in 2003"


Journal ArticleDOI
TL;DR: A theoretical explanation for the observed behavior of the Vicsek model, which proves to be a graphic example of a switched linear system which is stable, but for which there does not exist a common quadratic Lyapunov function.
Abstract: In a recent Physical Review Letters article, Vicsek et al. propose a simple but compelling discrete-time model of n autonomous agents (i.e., points or particles) all moving in the plane with the same speed but with different headings. Each agent's heading is updated using a local rule based on the average of its own heading plus the headings of its "neighbors." In their paper, Vicsek et al. provide simulation results which demonstrate that the nearest neighbor rule they are studying can cause all agents to eventually move in the same direction despite the absence of centralized coordination and despite the fact that each agent's set of nearest neighbors change with time as the system evolves. This paper provides a theoretical explanation for this observed behavior. In addition, convergence results are derived for several other similarly inspired models. The Vicsek model proves to be a graphic example of a switched linear system which is stable, but for which there does not exist a common quadratic Lyapunov function.

8,233 citations


Journal ArticleDOI
08 Aug 2003-Science
TL;DR: It is shown that disrupting antidepressant-induced neurogenesis blocks behavioral responses to antidepressants, suggesting that the behavioral effects of chronic antidepressants may be mediated by the stimulation of neuroGenesis in the hippocampus.
Abstract: Various chronic antidepressant treatments increase adult hippocampal neurogenesis, but the functional importance of this phenomenon remains unclear. Here, using genetic and radiological methods, we show that disrupting antidepressant-induced neurogenesis blocks behavioral responses to antidepressants. Serotonin 1A receptor null mice were insensitive to the neurogenic and behavioral effects of fluoxetine, a serotonin selective reuptake inhibitor. X-irradiation of a restricted region of mouse brain containing the hippocampus prevented the neurogenic and behavioral effects of two classes of antidepressants. These findings suggest that the behavioral effects of chronic antidepressants may be mediated by the stimulation of neurogenesis in the hippocampus.

4,116 citations


Journal ArticleDOI
21 Feb 2003-Cell
TL;DR: A core set of proteins including actin, Arp2/3 complex, profilin, capping protein, and ADF/cofilin can reconstitute the process in vitro, and mathematical models of the constituent reactions predict the rate of motion.

3,793 citations


Journal ArticleDOI
TL;DR: Risks in carriers were higher when based on index breast cancer cases diagnosed at <35 years of age and for variation in risk by mutation position for both genes, and some evidence for a reduction in risk in women from earlier birth cohorts is found.
Abstract: Germline mutations in BRCA1 and BRCA2 confer high risks of breast and ovarian cancer, but the average magnitude of these risks is uncertain and may depend on the context. Estimates based on multiple-case families may be enriched for mutations of higher risk and/or other familial risk factors, whereas risk estimates from studies based on cases unselected for family history have been imprecise. We pooled pedigree data from 22 studies involving 8,139 index case patients unselected for family history with female (86%) or male (2%) breast cancer or epithelial ovarian cancer (12%), 500 of whom had been found to carry a germline mutation in BRCA1 or BRCA2. Breast and ovarian cancer incidence rates for mutation carriers were estimated using a modified segregation analysis, based on the occurrence of these cancers in the relatives of mutation-carrying index case patients. The average cumulative risks in BRCA1-mutation carriers by age 70 years were 65% (95% confidence interval 44%-78%) for breast cancer and 39% (18%-54%) for ovarian cancer. The corresponding estimates for BRCA2 were 45% (31%-56%) and 11% (2.4%-19%). Relative risks of breast cancer declined significantly with age for BRCA1-mutation carriers (P trend.0012) but not for BRCA2-mutation carriers. Risks in carriers were higher when based on index breast cancer cases diagnosed at <35 years of age. We found some evidence for a reduction in risk in women from earlier birth cohorts and for variation in risk by mutation position for both genes. The pattern of cancer risks was similar to those found in multiple-case families, but their absolute magnitudes were lower, particularly for BRCA2. The variation in risk by age at diagnosis of index case is consistent with the effects of other genes modifying cancer risk in carriers.

3,384 citations


Journal ArticleDOI
15 Feb 2003-Cancer
TL;DR: This compilation of several large United States‐based databases comprising patients from 1950 to 1999 examines 13,715 carcinoid tumors and provides epidemiologic information regarding the natural history and evolution of the detection and diagnosis of this entity.
Abstract: were frequent in conjunction with small intestinal (29.0%), gastric (20.5%), colonic (20.0%), and appendiceal (18.2%) carcinoids. The highest percentages of nonlocalized lesions were noted for cecal (81.5‐ 83.2%) and pancreatic (71.9 ‐ 81.3%) carcinoids, whereas the highest percentage of localized disease was found among rectal (81.7%), gastric (67.5%), and bronchopulmonary (65.4%) carcinoids. The best 5-year survival rates were recorded for patients with rectal (88.3%), bronchopulmonary (73.5%), and appendiceal (71.0%) carcinoids; these tumors exhibited invasive growth or metastatic spread in 3.9%, 27.5%, and 38.8% of patients, respectively. CONCLUSIONS. Carcinoids appear to have increased in overall incidence over the past 30 years; for some sites, this trend has been evident for nearly half a century. Recent marked increases in gastric and rectal carcinoids and a concomitant decrease in appendiceal carcinoid incidence may be due in part to varying rules of registration among the compiled databases examined in this report or to improvements in diagnostic technology; increased awareness of and about carcinoid tumors also may play a significant role. In 12.9% of all patients with carcinoid, distant metastases already were evident at the time of diagnosis; the overall 5-year survival rate for all carcinoid tumors, regardless of site, was 67.2%. These findings bring into question the widely promulgated relative benignity of carcinoid disease. Certain carcinoid tumors, such as those of the rectum, appear to be over-represented among the black and Asian populations within the United States, suggesting the role of genetics in the development of this intriguing disease. Cancer 2003;97: 934 –59. © 2003 American Cancer Society. DOI 10.1002/cncr.11105

2,485 citations


Journal ArticleDOI
05 Dec 2003-Science
TL;DR: This map serves as a starting point for a systems biology modeling of multicellular organisms, including humans, and recapitulated known pathways, extended pathways, and uncovered previously unknown pathway components.
Abstract: Drosophila melanogaster is a proven model system for many aspects of human biology. Here we present a two-hybrid-based protein-interaction map of the fly proteome. A total of 10,623 predicted transcripts were isolated and screened against standard and normalized complementary DNA libraries to produce a draft map of 7048 proteins and 20,405 interactions. A computational method of rating two-hybrid interaction confidence was developed to refine this draft map to a higher confidence map of 4679 proteins and 4780 interactions. Statistical modeling of the network showed two levels of organization: a short-range organization, presumably corresponding to multiprotein complexes, and a more global organization, presumably corresponding to intercomplex connections. The network recapitulated known pathways, extended pathways, and uncovered previously unknown pathway components. This map serves as a starting point for a systems biology modeling of multicellular organisms, including humans.

2,414 citations


Journal ArticleDOI
TL;DR: In this paper, the authors used Monte Carlo realizations of different star formation histories, including starbursts of varying strength and a range of metallicities, to constrain the mean stellar ages of galaxies and the fractional stellar mass formed in bursts over the past few Gyr.
Abstract: We develop a new method to constrain the star formation histories, dust attenuation and stellar masses of galaxies. It is based on two stellar absorption-line indices, the 4000-A break strength and the Balmer absorption-line index Hδ A . Together, these indices allow us to constrain the mean stellar ages of galaxies and the fractional stellar mass formed in bursts over the past few Gyr. A comparison with broad-band photometry then yields estimates of dust attenuation and of stellar mass. We generate a large library of Monte Carlo realizations of different star formation histories, including starbursts of varying strength and a range of metallicities. We use this library to generate median likelihood estimates of burst mass fractions, dust attenuation strengths, stellar masses and stellar mass-to-light ratios for a sample of 122 808 galaxies drawn from the Sloan Digital Sky Survey. The typical 95 per cent confidence range in our estimated stellar masses is ′40 per cent. We study how the stellar mass-to-light ratios of galaxies vary as a function of absolute magnitude, concentration index and photometric passband and how dust attenuation varies as a function of absolute magnitude and 4000-A break strength. We also calculate how the total stellar mass of the present Universe is distributed over galaxies as a function of their mass, size, concentration, colour, burst mass fraction and surface mass density. We find that most of the stellar mass in the local Universe resides in galaxies that have, to within a factor of approximately 2, stellar masses ∼5 x 10 1 0 M O ., half-light radii ∼3 kpc and half-light surface mass densities ∼10 9 M O .kpc - 2 . The distribution of D n (4000) is strongly bimodal, showing a clear division between galaxies dominated by old stellar populations and galaxies with more recent star formation.

2,407 citations


Journal ArticleDOI
14 Feb 2003-Science
TL;DR: A second mechanism of immune induction by TLRs is described, which is independent of effects on costimulation, and dependent in part on interleukin-6, which was induced byTLRs upon recognition of microbial products.
Abstract: Toll-like receptors (TLRs) control activation of adaptive immune responses by antigen-presenting cells (APCs). However, initiation of adaptive immune responses is also controlled by regulatory T cells (TR cells), which act to prevent activation of autoreactive T cells. Here we describe a second mechanism of immune induction by TLRs, which is independent of effects on costimulation. Microbial induction of the Toll pathway blocked the suppressive effect of CD4+CD25+ TR cells, allowing activation of pathogen-specific adaptive immune responses. This block of suppressor activity was dependent in part on interleukin-6, which was induced by TLRs upon recognition of microbial products.

2,107 citations


Journal ArticleDOI
16 May 2003-Science
TL;DR: Elderly study participants were markedly insulin-resistant as compared with young controls, and this resistance was attributable to reduced insulin-stimulated muscle glucose metabolism, which supports the hypothesis that an age-associated decline in mitochondrial function contributes to insulin resistance in the elderly.
Abstract: Insulin resistance is a major factor in the pathogenesis of type 2 diabetes in the elderly. To investigate how insulin resistance arises, we studied healthy, lean, elderly and young participants matched for lean body mass and fat mass. Elderly study participants were markedly insulin-resistant as compared with young controls, and this resistance was attributable to reduced insulin-stimulated muscle glucose metabolism. These changes were associated with increased fat accumulation in muscle and liver tissue assessed by 1H nuclear magnetic resonance (NMR) spectroscopy, and with a approximately 40% reduction in mitochondrial oxidative and phosphorylation activity, as assessed by in vivo 13C/31P NMR spectroscopy. These data support the hypothesis that an age-associated decline in mitochondrial function contributes to insulin resistance in the elderly.

1,984 citations


Journal ArticleDOI
Scott W. Woods1
TL;DR: These equivalency estimates may be useful for clinical and research purposes and the source of the dose equivalency estimation is evidence-based and consistent across medication.
Abstract: Background Several clinical and research applications require an estimation of therapeutic dose equivalence across antipsychotic medications. Since the advent of the newer atypical antipsychotics, new dose equivalent estimations have been needed. Method The reported minimum effective dose was identified for each newer atypical antipsychotic medication and for haloperidol across all available fixed-dose placebo-controlled studies. Reported minimum effective dose equivalence ratios to haloperidol were then converted to chlorpromazine equivalents using the "2 mg of haloperidol equals 100 mg of chlorpromazine" convention. Data sources and study selection To identify the fixed-dose studies, the following sources were searched until June 2002: MEDLINE, the bibliographies of identified reports, published meta-analyses and reviews, Cochrane reviews, Freedom of Information Act material available from the Food and Drug Administration, and abstracts from several scientific meetings from 1997 to 2002. Results Doses equivalent to 100 mg/day of chlorpromazine were 2 mg/day for risperidone, 5 mg/day for olanzapine, 75 mg/day for quetiapine, 60 mg/day for ziprasidone, and 7.5 mg/day for aripiprazole. Conclusion These equivalency estimates may be useful for clinical and research purposes. The source of the dose equivalency estimation is evidence-based and consistent across medication.

1,939 citations


Journal ArticleDOI
25 Sep 2003-Nature
TL;DR: In this paper, the authors demonstrate a technique that allows direct electrical measurements of microwave-frequency dynamics in individual nanomagnets, propelled by a d.c. spin-polarized current.
Abstract: The recent discovery that a spin-polarized electrical current can apply a large torque to a ferromagnet, through direct transfer of spin angular momentum, offers the possibility of manipulating magnetic-device elements without applying cumbersome magnetic fields. However, a central question remains unresolved: what type of magnetic motions can be generated by this torque? Theory predicts that spin transfer may be able to drive a nanomagnet into types of oscillatory magnetic modes not attainable with magnetic fields alone, but existing measurement techniques have provided only indirect evidence for dynamical states. The nature of the possible motions has not been determined. Here we demonstrate a technique that allows direct electrical measurements of microwave-frequency dynamics in individual nanomagnets, propelled by a d.c. spin-polarized current. We show that spin transfer can produce several different types of magnetic excitation. Although there is no mechanical motion, a simple magnetic-multilayer structure acts like a nanoscale motor; it converts energy from a d.c. electrical current into high-frequency magnetic rotations that might be applied in new devices including microwave sources and resonators.

Journal ArticleDOI
TL;DR: This work merges many of the available yeast protein-abundance datasets, using the resulting larger 'meta-dataset' to find correlations between protein and mRNA expression, both globally and within smaller categories.
Abstract: Attempts to correlate protein abundance with mRNA expression levels have had variable success. We review the results of these comparisons, focusing on yeast. In the process, we survey experimental techniques for determining protein abundance, principally two-dimensional gel electrophoresis and mass-spectrometry. We also merge many of the available yeast protein-abundance datasets, using the resulting larger 'meta-dataset' to find correlations between protein and mRNA expression, both globally and within smaller categories.

Journal ArticleDOI
TL;DR: Long-term combination therapy with doxazosin and finasteride was safe and reduced the risk of overall clinical progression of benign prostatic hyperplasia significantly more than did treatment with either drug alone.
Abstract: background Benign prostatic hyperplasia is commonly treated with alpha-adrenergic–receptor antagonists (alpha-blockers) or 5 a -reductase inhibitors. The long-term effect of these drugs, singly or combined, on the risk of clinical progression is unknown. methods We conducted a long-term, double-blind trial (mean follow-up, 4.5 years) involving 3047 men to compare the effects of placebo, doxazosin, finasteride, and combination therapy on measures of the clinical progression of benign prostatic hyperplasia. results The risk of overall clinical progression — defined as an increase above base line of at least 4 points in the American Urological Association symptom score, acute urinary retention, urinary incontinence, renal insufficiency, or recurrent urinary tract infection — was significantly reduced by doxazosin (39 percent risk reduction, P<0.001) and finasteride (34 percent risk reduction, P=0.002), as compared with placebo. The reduction in risk associated with combination therapy (66 percent for the comparison with placebo, P<0.001) was significantly greater than that associated with doxazosin (P<0.001) or finasteride (P<0.001) alone. The risks of acute urinary retention and the need for invasive therapy were significantly reduced by combination therapy (P<0.001) and finasteride (P<0.001) but not by doxazosin. Doxazosin (P<0.001), finasteride (P =0.001), and combination therapy (P<0.001) each resulted in significant improvement in symptom scores, with combination therapy being superior to both doxazosin (P=0.006) and finasteride (P<0.001) alone. conclusions Long-term combination therapy with doxazosin and finasteride was safe and reduced the risk of overall clinical progression of benign prostatic hyperplasia significantly more than did treatment with either drug alone. Combination therapy and finasteride alone reduced the long-term risk of acute urinary retention and the need for invasive therapy.

Journal ArticleDOI
18 Jun 2003-JAMA
TL;DR: The intervention improved depression and social isolation, although the relative improvement in the psychosocial intervention group compared with the usual care group was less than expected due to substantial improvement in usual care patients.
Abstract: CONTEXT Depression and low perceived social support (LPSS) after myocardial infarction (MI) are associated with higher morbidity and mortality, but little is known about whether this excess risk can be reduced through treatment. OBJECTIVE To determine whether mortality and recurrent infarction are reduced by treatment of depression and LPSS with cognitive behavior therapy (CBT), supplemented with a selective serotonin reuptake inhibitor (SSRI) antidepressant when indicated, in patients enrolled within 28 days after MI. DESIGN, SETTING, AND PATIENTS Randomized clinical trial conducted from October 1996 to April 2001 in 2481 MI patients (1084 women, 1397 men) enrolled from 8 clinical centers. Major or minor depression was diagnosed by modified Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and severity by the 17-item Hamilton Rating Scale for Depression (HRSD); LPSS was determined by the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Social Support Instrument (ESSI). Random allocation was to usual medical care or CBT-based psychosocial intervention. INTERVENTION Cognitive behavior therapy was initiated at a median of 17 days after the index MI for a median of 11 individual sessions throughout 6 months, plus group therapy when feasible, with SSRIs for patients scoring higher than 24 on the HRSD or having a less than 50% reduction in Beck Depression Inventory scores after 5 weeks. MAIN OUTCOME MEASURES Composite primary end point of death or recurrent MI; secondary outcomes included change in HRSD (for depression) or ESSI scores (for LPSS) at 6 months. RESULTS Improvement in psychosocial outcomes at 6 months favored treatment: mean (SD) change in HRSD score, -10.1 (7.8) in the depression and psychosocial intervention group vs -8.4 (7.7) in the depression and usual care group (P<.001); mean (SD) change in ESSI score, 5.1 (5.9) in the LPSS and psychosocial intervention group vs 3.4 (6.0) in the LPSS and usual care group (P<.001). After an average follow-up of 29 months, there was no significant difference in event-free survival between usual care (75.9%) and psychosocial intervention (75.8%). There were also no differences in survival between the psychosocial intervention and usual care arms in any of the 3 psychosocial risk groups (depression, LPSS, and depression and LPSS patients). CONCLUSIONS The intervention did not increase event-free survival. The intervention improved depression and social isolation, although the relative improvement in the psychosocial intervention group compared with the usual care group was less than expected due to substantial improvement in usual care patients.

Journal ArticleDOI
TL;DR: The data demonstrate that Rheb acts downstream of TSC1/TSC2 and upstream of mTOR to regulate cell growth and plays an essential role in regulation of S6K and 4EBP1 in response to nutrients and cellular energy status.
Abstract: Tuberous sclerosis complex (TSC) is a genetic disease caused by mutation in either TSC1 or TSC2. The TSC1 and TSC2 gene products form a functional complex and inhibit phosphorylation of S6K and 4EBP1. These functions of TSC1/TSC2 are likely mediated by mTOR. Here we report that TSC2 is a GTPase-activating protein (GAP) toward Rheb, a Ras family GTPase. Rheb stimulates phosphorylation of S6K and 4EBP1. This function of Rheb is blocked by rapamycin and dominant-negative mTOR. Rheb stimulates the phosphorylation of mTOR and plays an essential role in regulation of S6K and 4EBP1 in response to nutrients and cellular energy status. Our data demonstrate that Rheb acts downstream of TSC1/TSC2 and upstream of mTOR to regulate cell growth.

Journal ArticleDOI
TL;DR: The acquisition of a T674I resistance mutation at the time of relapse demonstrates that FIP1L1-PDGFRalpha is the target of imatinib, and data indicate that the deletion of genetic material may result in gain-of-function fusion proteins.
Abstract: Background Idiopathic hypereosinophilic syndrome involves a prolonged state of eosinophilia associated with organ dysfunction. It is of unknown cause. Recent reports of responses to imatinib in patients with the syndrome suggested that an activated kinase such as ABL, platelet-derived growth factor receptor (PDGFR), or KIT, all of which are inhibited by imatinib, might be the cause. Methods We treated 11 patients with the hypereosinophilic syndrome with imatinib and identified the molecular basis for the response. Results Nine of the 11 patients treated with imatinib had responses lasting more than three months in which the eosinophil count returned to normal. One such patient had a complex chromosomal abnormality, leading to the identification of a fusion of the Fip1-like 1 (FIP1L1) gene to the PDGFRα (PDGFRA) gene generated by an interstitial deletion on chromosome 4q12. FIP1L1-PDGFRα is a constitutively activated tyrosine kinase that transforms hematopoietic cells and is inhibited by imatinib (50 perce...

Journal ArticleDOI
Mary E. Tinetti1
TL;DR: A 79-year-old woman with a history of congestive heart failure, arthritis, depression, and difficulty sleeping presents for a follow-up visit, and her daughter reports that the patient has fallen twice during the past six months.
Abstract: A 79-year-old woman with a history of congestive heart failure, arthritis, depression, and difficulty sleeping presents for a follow-up visit. She takes several prescription medications, including an antidepressant, a diuretic, an angiotensin-converting–enzyme inhibitor, and a beta-blocker, as well as over-the-counter sleep and allergy medications. Her chronic conditions appear to be stable. Her daughter reports that the patient has fallen twice during the past six months. What can be done to prevent future falls?

Journal ArticleDOI
20 Feb 2003-Neuron
TL;DR: Using electrophysiological recordings, ghrelin stimulated the activity of arcuate NPY neurons and mimicked the effect of NPY in the paraventricular nucleus of the hypothalamus (PVH), thus representing a novel regulatory circuit controlling energy homeostasis.

Journal ArticleDOI
01 Mar 2003-Emotion
TL;DR: The MSCEIT achieved reasonable reliability, and confirmatory factor analysis supported theoretical models of EI, helping clarify issues raised in earlier articles published in Emotion.
Abstract: Does a recently introduced ability scale adequately measure emotional intelligence (EI) skills? Using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT; J. D. Mayer, P. Salovey, & D. R. Caruso, 2002b), the authors examined (a) whether members of a general standardization sample and emotions experts identified the same test answers as correct, (b) the test's reliability, and (c) the possible factor structures of EI. Twenty-one emotions experts endorsed many of the same answers, as did 2,112 members of the standardization sample, and exhibited superior agreement, particularly when research provides clearer answers to test questions (e.g., emotional perception in faces). The MSCEIT achieved reasonable reliability, and confirmatory factor analysis supported theoretical models of EI. These findings help clarify issues raised in earlier articles published in Emotion.

Journal ArticleDOI
TL;DR: An exploration of developmental changes in neurocircuitry involved in impulse control has significant implications for understanding adolescent behavior, addiction vulnerability, and the prevention of addiction in adolescence and adulthood.
Abstract: Objective: Epidemiological studies indicate that experimentation with addictive drugs and onset of addictive disorders is primarily concentrated in adolescence and young adulthood. The authors describe basic and clinical data supporting adolescent neurodevelopment as a biologically critical period of greater vulnerability for experimentation with substances and acquisition of substance use disorders. Method: The authors reviewed recent literature regarding neurocircuitry underlying motivation, impulsivity, and addiction, with a focus on studies investigating adolescent neurodevelopment. Results: Adolescent neurodevelopment occurs in brain regions associated with motivation, impulsivity, and addiction. Adolescent impulsivity and/or novelty seeking as a transitional trait behavior can be explained in part by maturational changes in frontal cortical and subcortical monoaminergic systems. These developmental processes may advantageously promote learning drives for adaptation to adult roles but may also confer greater vulnerability to the addictive actions of drugs. Conclusions: An exploration of developmental changes in neurocircuitry involved in impulse control has significant implications for understanding adolescent behavior, addiction vulnerability, and the prevention of addiction in adolescence and adulthood.

Journal ArticleDOI
22 Jan 2003-JAMA
TL;DR: In this article, the authors reviewed original, quantitative studies on the extent, impact, and management of financial conflicts of interest in biomedical research and concluded that financial relationships among industry, scientific investigators, and academic institutions are widespread.
Abstract: ContextDespite increasing awareness about the potential impact of financial conflicts of interest on biomedical research, no comprehensive synthesis of the body of evidence relating to financial conflicts of interest has been performed.ObjectiveTo review original, quantitative studies on the extent, impact, and management of financial conflicts of interest in biomedical research.Data SourcesStudies were identified by searching MEDLINE (January 1980-October 2002), the Web of Science citation database, references of articles, letters, commentaries, editorials, and books and by contacting experts.Study SelectionAll English-language studies containing original, quantitative data on financial relationships among industry, scientific investigators, and academic institutions were included. A total of 1664 citations were screened, 144 potentially eligible full articles were retrieved, and 37 studies met our inclusion criteria.Data ExtractionOne investigator (J.E.B.) extracted data from each of the 37 studies. The main outcomes were the prevalence of specific types of industry relationships, the relation between industry sponsorship and study outcome or investigator behavior, and the process for disclosure, review, and management of financial conflicts of interest.Data SynthesisApproximately one fourth of investigators have industry affiliations, and roughly two thirds of academic institutions hold equity in start-ups that sponsor research performed at the same institutions. Eight articles, which together evaluated 1140 original studies, assessed the relation between industry sponsorship and outcome in original research. Aggregating the results of these articles showed a statistically significant association between industry sponsorship and pro-industry conclusions (pooled Mantel-Haenszel odds ratio, 3.60; 95% confidence interval, 2.63-4.91). Industry sponsorship was also associated with restrictions on publication and data sharing. The approach to managing financial conflicts varied substantially across academic institutions and peer-reviewed journals.ConclusionsFinancial relationships among industry, scientific investigators, and academic institutions are widespread. Conflicts of interest arising from these ties can influence biomedical research in important ways.

Journal ArticleDOI
TL;DR: In this paper, the authors examined the validity of the measurement model and factor structure of Bass and Avolio's Multifactor Leadership Questionnaire (MLQ) (Form 5X).
Abstract: In this study, we examined the validity of the measurement model and factor structure of Bass and Avolio’s Multifactor Leadership Questionnaire (MLQ) (Form 5X). We hypothesized that evaluations of leadership—and hence the psychometric properties of leadership instruments—may be affected by the context in which leadership is observed and evaluated. Using largely homogenous business samples consisting of 2279 pooled male and 1089 pooled female raters who evaluated same-gender leaders, we found support for the nine-factor leadership model proposed by Bass and Avolio. The model was configurally and partially metrically invariant—suggesting that the same constructs were validly measured in the male and female groups. Mean differences were found between the male and female samples on four leadership factors (Study 1). Next, using factor-level data of 18 independently gathered samples (N=6525 raters) clustered into prototypically homogenous contexts, we tested the nine-factor model and found it was stable (i.e., fully invariant) within homogenous contexts (Study 2). The contextual factors comprised environmental risk, leader–follower gender, and leader hierarchical level. Implications for use of the MLQ and nine-factor model are discussed.

Journal ArticleDOI
TL;DR: Data is presented suggesting that excellent interrater reliability can be established for diagnosis in a day-and-a-half-long training workshop and on the Structured Interview for Prodromal Syndromes and the Scale of ProDromal Symptoms.
Abstract: As the number of studies related to the early identification of and intervention in the schizophrenia prodrome continues to grow, it becomes increasingly critical to develop methods to diagnose this new clinical entity with validity. Furthermore, given the low incidence of patients and the need for multisite collaboration, diagnostic and symptom severity reliability is also crucial. This article provides further data on these psychometric parameters for the prodromal assessment instruments developed by the Prevention through Risk Identification, Management, and Education (PRIME) prodromal research team at Yale University: the Structured Interview for Prodromal Syndromes and the Scale of Prodromal Symptoms. It also presents data suggesting that excellent interrater reliability can be established for diagnosis in a day-and-a-half-long training workshop.

Journal ArticleDOI
TL;DR: The current definition of developmental dyslexia agreed on by the work group updates and expands on the working definition from 1994.
Abstract: This paper elaborates on the components of a working definition of developmental dyslexia. It follows the general format of a paper by Lyon published in Annals of Dyslexia in 1995, which elaborated on a working definition proposed in 1994 (Lyon, 1995). The current definition agreed on by the work group updates and expands on the working definition from 1994.

Journal ArticleDOI
21 Oct 2003-Nature
TL;DR: Two crystal structures of the glucocorticoid receptor DNA-binding domain complexed with DNA are reported, which have a globular fold which contains two Zn-nucleated substructures of distinct conformation and function.
Abstract: Two crystal structures of the glucocorticoid receptor DNA-binding domain complexed with DNA are reported. The domain has a globular fold which contains two Zn-nucleated substructures of distinct conformation and function. When it binds DNA, the domain dimerizes, placing the subunits in adjacent major grooves. In one complex, the DNA has the symmetrical consensus target sequence; in the second, the central spacing between the target's half-sites is larger by one base pair. This results in one subunit interacting specifically with the consensus target half-site and the other nonspecifically with a noncognate element. The DNA-induced dimer fixes the separation of the subunits' recognition surfaces so that the spacing between the half-sites becomes a critical feature of the target sequence's identity.

Journal ArticleDOI
TL;DR: Active surveillance cultures are essential to identify the reservoir for spread of MRSA and VRE infections and make control possible using the CDC's long-recommended contact precautions, demonstrating consistency of evidence, high strength of association, reversibility, dose gradient, and specificity for control with this approach.
Abstract: patients with MRSA or VRE usually acquire it via spread. The CDC has long-recommended contact precautions for patients colonized or infected with such pathogens. Most facilities have required this as policy, but have not actively identified colonized patients with sur veillance cultures, leaving most colonized patients undetected and unisolated. Many studies have shown control of endemic and/or epidemic MRSA and VRE infections using surveillance cultures and contact precautions, demonstrating consistency of evidence, high strength of association, reversibility, a dose gradient, and specificity for control with this approach. Adjunctive control measures are also discussed. CONCLUSION: Active surveillance cultures are essential to identify the reservoir for spread of MRSA and VRE infections and make control possible using the CDC’s long-recommended contact precautions (Infect Control Hosp Epidemiol 2003;24:362-386).

PatentDOI
09 Jan 2003-Cell
TL;DR: IRAK-M regulates TLR signaling and innate immune homeostasis and prevents dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAk-TRAF6 complexes.

Journal ArticleDOI
TL;DR: In this article, the average soil carbon density of mangrove swamps (0.055 ± 0.004 g cm−3) is significantly higher than the salt marsh average ( 0.039 − 0.003 g cm −3) due to increased decay rates at higher temperatures.
Abstract: [1] Wetlands represent the largest component of the terrestrial biological carbon pool and thus play an important role in global carbon cycles. Most global carbon budgets, however, have focused on dry land ecosystems that extend over large areas and have not accounted for the many small, scattered carbon-storing ecosystems such as tidal saline wetlands. We compiled data for 154 sites in mangroves and salt marshes from the western and eastern Atlantic and Pacific coasts, as well as the Indian Ocean, Mediterranean Ocean, and Gulf of Mexico. The set of sites spans a latitudinal range from 22.4°S in the Indian Ocean to 55.5°N in the northeastern Atlantic. The average soil carbon density of mangrove swamps (0.055 ± 0.004 g cm−3) is significantly higher than the salt marsh average (0.039 ± 0.003 g cm−3). Soil carbon density in mangrove swamps and Spartina patens marshes declines with increasing average annual temperature, probably due to increased decay rates at higher temperatures. In contrast, carbon sequestration rates were not significantly different between mangrove swamps and salt marshes. Variability in sediment accumulation rates within marshes is a major control of carbon sequestration rates masking any relationship with climatic parameters. Globally, these combined wetlands store at least 44.6 Tg C yr−1 and probably more, as detailed areal inventories are not available for salt marshes in China and South America. Much attention has been given to the role of freshwater wetlands, particularly northern peatlands, as carbon sinks. In contrast to peatlands, salt marshes and mangroves release negligible amounts of greenhouse gases and store more carbon per unit area.

Journal ArticleDOI
17 Oct 2003-Science
TL;DR: This work develops an approach using Bayesian networks to predict protein-protein interactions genome-wide in yeast, and observes that at given levels of sensitivity, the predictions are more accurate than the existing high-throughput experimental data sets.
Abstract: We have developed an approach using Bayesian networks to predict protein-protein interactions genome-wide in yeast. Our method naturally weights and combines into reliable predictions genomic features only weakly associated with interaction (e.g., messenger RNAcoexpression, coessentiality, and colocalization). In addition to de novo predictions, it can integrate often noisy, experimental interaction data sets. We observe that at given levels of sensitivity, our predictions are more accurate than the existing high-throughput experimental data sets. We validate our predictions with TAP (tandem affinity purification) tagging experiments. Our analysis, which gives a comprehensive view of yeast interactions, is available at genecensus.org/intint.

Proceedings ArticleDOI
09 Jul 2003
TL;DR: In this paper, a simple, cheat-proof, credit-based system for stimulating cooperation among selfish nodes in mobile ad hoc networks is proposed, which does not require any tamper-proof hardware at any node.
Abstract: Mobile ad hoc networking has been an active research area for several years. How to stimulate cooperation among selfish mobile nodes, however, is not well addressed yet. In this paper, we propose Sprite, a simple, cheat-proof, credit-based system for stimulating cooperation among selfish nodes in mobile ad hoc networks. Our system provides incentive for mobile nodes to cooperate and report actions honestly. Compared with previous approaches, our system does not require any tamper-proof hardware at any node. Furthermore, we present a formal model of our system and prove its properties. Evaluations of a prototype implementation show that the overhead of our system is small. Simulations and analysis show that mobile nodes can cooperate and forward each other's messages, unless the resource of each node is extremely low.