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Institution

Tufts University

EducationMedford, Massachusetts, United States
About: Tufts University is a education organization based out in Medford, Massachusetts, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 32800 authors who have published 66881 publications receiving 3451152 citations. The organization is also known as: Tufts College & Universitatis Tuftensis.


Papers
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Journal ArticleDOI
TL;DR: Projections from populations of leptin‐responsive neurons in the mediobasal hypothalamus to MCH and ORX cells in the LHA may link peripheral metabolic cues with the cortical mantle and may play a critical role in the regulation of feeding behavior and body weight.
Abstract: Recent studies have identified several neuropeptide systems in the hypothalamus that are critical in the regulation of body weight. The lateral hypothalamic area (LHA) has long been considered essential in regulating food intake and body weight. Two neuropeptides, melanin-concentrating hormone (MCH) and the orexins (ORX), are localized in the LHA and provide diffuse innervation of the neuraxis, including monosynaptic projections to the cerebral cortex and autonomic preganglionic neurons. Therefore, MCH and ORX neurons may regulate both cognitive and autonomic aspects of food intake and body weight regulation. The arcuate nucleus also is critical in the regulation of body weight, because it contains neurons that express leptin receptors, neuropeptide Y (NPY), alpha-melanin-stimulating hormone (alpha-MSH), and agouti-related peptide (AgRP). In this study, we examined the relationships of these peptidergic systems by using dual-label immunohistochemistry or in situ hybridization in rat, mouse, and human brains. In the normal rat, mouse, and human brain, ORX and MCH neurons make up segregated populations. In addition, we found that AgRP- and NPY-immunoreactive neurons are present in the medial division of the human arcuate nucleus, whereas alpha-MSH-immunoreactive neurons are found in the lateral arcuate nucleus. In humans, AgRP projections were widespread in the hypothalamus, but they were especially dense in the paraventricular nucleus and the perifornical area. Moreover, in both rat and human, MCH and ORX neurons receive innervation from NPY-, AgRP-, and alpha-MSH-immunoreactive fibers. Projections from populations of leptin-responsive neurons in the mediobasal hypothalamus to MCH and ORX cells in the LHA may link peripheral metabolic cues with the cortical mantle and may play a critical role in the regulation of feeding behavior and body weight.

842 citations

Journal ArticleDOI
TL;DR: The importance of developmental stage and the realization that exposure to a presumptive "safe" dose of chemical may impact a life stage when there is normally no endogenous hormone exposure are emphasized, thereby underscoring the potential for very low-dose EDC exposures to have potent and irreversible effects.
Abstract: An endocrine-disrupting chemical (EDC) is an exogenous chemical, or mixture of chemicals, that can interfere with any aspect of hormone action. The potential for deleterious effects of EDC must be considered relative to the regulation of hormone synthesis, secretion, and actions and the variability in regulation of these events across the life cycle. The developmental age at which EDC exposures occur is a critical consideration in understanding their effects. Because endocrine systems exhibit tissue-, cell-, and receptor-specific actions during the life cycle, EDC can produce complex, mosaic effects. This complexity causes difficulty when a static approach to toxicity through endocrine mechanisms driven by rigid guidelines is used to identify EDC and manage risk to human and wildlife populations. We propose that principles taken from fundamental endocrinology be employed to identify EDC and manage their risk to exposed populations. We emphasize the importance of developmental stage and, in particular, the realization that exposure to a presumptive “safe” dose of chemical may impact a life stage when there is normally no endogenous hormone exposure, thereby underscoring the potential for very low-dose EDC exposures to have potent and irreversible effects. Finally, with regard to the current program designed to detect putative EDC, namely, the Endocrine Disruptor Screening Program, we offer recommendations for strengthening this program through the incorporation of basic endocrine principles to promote further understanding of complex EDC effects, especially due to developmental exposures.

839 citations

Journal ArticleDOI
29 Apr 1994-Science
TL;DR: It is demonstrated that GM- CSF is not an essential growth factor for basal hematopoiesis and an unexpected, critical role for GM-CSF in pulmonary homeostasis is revealed.
Abstract: The in vivo function of murine granulocyte-macrophage colony-stimulating factor (GM-CSF) was investigated in mice, carrying a null allele of the GM-CSF gene, that were generated by gene targeting techniques in embryonic stem cells. Although steady-state hematopoiesis was unimpaired in homozygous mutant animals, all animals developed the progressive accumulation of surfactant lipids and proteins in the alveolar space, the defining characteristic of the idiopathic human disorder pulmonary alveolar proteinosis. Extensive lymphoid hyperplasia associated with lung airways and blood vessels was also found, yet no infectious agents could be detected. These results demonstrate that GM-CSF is not an essential growth factor for basal hematopoiesis and reveal an unexpected, critical role for GM-CSF in pulmonary homeostasis.

839 citations

Journal ArticleDOI
TL;DR: In a survey of meta-analyses, the authors found that only 7% to 18% of the articles that employed funnel-plot asymmetry tests were significant in 7%-18% of them.
Abstract: Background: Statistical tests for funnel-plot asymmetry are common in meta-analyses. Inappropriate application can generate misleading inferences about publication bias. We aimed to measure, in a survey of meta-analyses, how frequently the application of these tests would be not meaningful or inappropriate. Methods: We evaluated all meta-analyses of binary outcomes with e 3 studies in the Cochrane Database of Systematic Reviews (2003, issue 2). A separate, restricted analysis was confined to the largest meta-analysis in each of the review articles. In each meta-analysis, we assessed whether criteria to apply asymmetry tests were met: no significant heterogeneity, I2 4. We performed a correlation and 2 regression asymmetry tests and evaluated their concordance. Finally, we sampled 60 meta-analyses from print journals in 2005 that cited use of the standard regression test. Results: A total of 366 of 6873 (5%) and 98 of 846 meta-analyses (12%) in the wider and restricted Cochrane data set, respectively, would have qualified for use of asymmetry tests. Asymmetry test results were significant in 7%–18% of the meta-analyses. Concordance between the 3 tests was modest (estimated k 0.33–0.66). Of the 60 journal meta-analyses, 7 (12%) would qualify for asymmetry tests; all 11 claims for identification of publication bias were made in the face of large and significant heterogeneity. Interpretation: Statistical conditions for employing asymmetry tests for publication bias are absent from most meta-analyses; yet, in medical journals these tests are performed often and interpreted erroneously.

838 citations

Book ChapterDOI
Mark Kachanov1
TL;DR: In this article, the impact of interactions on individual cracks, particularly on the stress intensity factors (SIFs), and the effective elastic properties of solids with many cracks are discussed.
Abstract: Publisher Summary This chapter discusses some basic problems in mechanics of elastic solids containing multiple cracks. A number of mathematical aspects that frequently constitute fields of their own (like various numerical techniques) are discussed very briefly in the chapter. The focus is on physically important effects produced by crack interactions and to present results in the simplest form possible. The problems considered in this chapter can be divided into two groups: (1) The impact of interactions on individual cracks, particularly on the stress intensity factors (SIFs), and (2) the effective elastic properties of solids with many cracks. Problems of the first group are, generally, relevant for the fracture-related considerations; solutions are sensitive to the positions of individual cracks. Problems of the second group deal with the volume average quantities; they are relatively insensitive to the information on individual cracks. The chapter discusses, in this connection, whether correlations exist between these two groups of quantities; in particular, whether microcracking can be reliably monitored by measuring changes in the effective elastic moduli.

838 citations


Authors

Showing all 33110 results

NameH-indexPapersCitations
Walter C. Willett3342399413322
Frank B. Hu2501675253464
Ralph B. D'Agostino2261287229636
John Q. Trojanowski2261467213948
Peter Libby211932182724
David Baltimore203876162955
Eric B. Rimm196988147119
Lewis C. Cantley196748169037
Bernard Rosner1901162147661
Charles A. Dinarello1901058139668
William B. Kannel188533175659
Scott M. Grundy187841231821
John P. A. Ioannidis1851311193612
David H. Weinberg183700171424
Joel Schwartz1831149109985
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023100
2022467
20213,335
20203,065
20192,806
20182,618