Institution
University of Vermont
Education•Burlington, Vermont, United States•
About: University of Vermont is a education organization based out in Burlington, Vermont, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 17592 authors who have published 38251 publications receiving 1609874 citations. The organization is also known as: UVM & University of Vermont and State Agricultural College.
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TL;DR: It is reported here that CD3-induced proliferation and interleukin 2 production by human T cells are blocked by inhibitors of caspase activity, extending the role of death receptors to the promotion of T cell growth in a casp enzyme-dependent manner.
Abstract: Triggering of Fas (CD95) by its ligand (FasL) rapidly induces cell death via recruitment of the adaptor protein Fas-associated death domain (FADD), resulting in activation of a caspase cascade It was thus surprising that T lymphocytes deficient in FADD were reported recently to be not only resistant to FasL-mediated apoptosis, but also defective in their proliferative capacity This finding suggested potentially dual roles of cell growth and death for Fas and possibly other death receptors We report here that CD3-induced proliferation and interleukin 2 production by human T cells are blocked by inhibitors of caspase activity This is paralleled by rapid cleavage of caspase-8 after CD3 stimulation, but no detectable processing of caspase-3 during the same interval The caspase contribution to T cell activation may occur via TCR-mediated upregulation of FasL, as Fas-Fc blocked T cell proliferation, whereas soluble FasL augmented CD3-induced proliferation These findings extend the role of death receptors to the promotion of T cell growth in a caspase-dependent manner
483 citations
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Memorial Sloan Kettering Cancer Center1, City of Hope National Medical Center2, University of South Florida3, University of Vermont4, University of California, San Francisco5, MedStar Washington Hospital Center6, St. Joseph Hospital7, Washington University in St. Louis8, University of California, Irvine9, University of Nebraska Medical Center10, Oregon Health & Science University11, University of Chicago12, Cleveland Clinic13
TL;DR: Delivery of mFOLFOX6 after chemoradiation and before total mesorectal excision has the potential to increase the proportion of patients eligible for less invasive treatment strategies; this strategy is being tested in phase 3 clinical trials.
Abstract: Summary Background Patients with locally advanced rectal cancer who achieve a pathological complete response to neoadjuvant chemoradiation have an improved prognosis. The need for surgery in these patients has been questioned, but the proportion of patients achieving a pathological complete response is small. We aimed to assess whether adding cycles of mFOLFOX6 between chemoradiation and surgery increased the proportion of patients achieving a pathological complete response. Methods We did a phase 2, non-randomised trial consisting of four sequential study groups of patients with stage II–III locally advanced rectal cancer at 17 institutions in the USA and Canada. All patients received chemoradiation (fluorouracil 225 mg/m 2 per day by continuous infusion throughout radiotherapy, and 45·0 Gy in 25 fractions, 5 days per week for 5 weeks, followed by a minimum boost of 5·4 Gy). Patients in group 1 had total mesorectal excision 6–8 weeks after chemoradiation. Patients in groups 2–4 received two, four, or six cycles of mFOLFOX6, respectively, between chemoradiation and total mesorectal excision. Each cycle of mFOLFOX6 consisted of racemic leucovorin 200 mg/m 2 or 400 mg/m 2 , according to the discretion of the treating investigator, oxaliplatin 85 mg/m 2 in a 2-h infusion, bolus fluorouracil 400 mg/m 2 on day 1, and a 46-h infusion of fluorouracil 2400 mg/m 2 . The primary endpoint was the proportion of patients who achieved a pathological complete response, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00335816. Findings Between March 24, 2004, and Nov 16, 2012, 292 patients were registered, 259 of whom (60 in group 1, 67 in group 2, 67 in group 3, and 65 in group 4) met criteria for analysis. 11 (18%, 95% CI 10–30) of 60 patients in group 1, 17 (25%, 16–37) of 67 in group 2, 20 (30%, 19–42) of 67 in group 3, and 25 (38%, 27–51) of 65 in group 4 achieved a pathological complete response (p=0·0036). Study group was independently associated with pathological complete response (group 4 compared with group 1 odds ratio 3·49, 95% CI 1·39–8·75; p=0·011). In group 2, two (3%) of 67 patients had grade 3 adverse events associated with the neoadjuvant administration of mFOLFOX6 and one (1%) had a grade 4 adverse event; in group 3, 12 (18%) of 67 patients had grade 3 adverse events; in group 4, 18 (28%) of 65 patients had grade 3 adverse events and five (8%) had grade 4 adverse events. The most common grade 3 or higher adverse events associated with the neoadjuvant administration of mFOLFOX6 across groups 2–4 were neutropenia (five in group 3 and six in group 4) and lymphopenia (three in group 3 and four in group 4). Across all study groups, 25 grade 3 or worse surgery-related complications occurred (ten in group 1, five in group 2, three in group 3, and seven in group 4); the most common were pelvic abscesses (seven patients) and anastomotic leaks (seven patients). Interpretation Delivery of mFOLFOX6 after chemoradiation and before total mesorectal excision has the potential to increase the proportion of patients eligible for less invasive treatment strategies; this strategy is being tested in phase 3 clinical trials. Funding National Institutes of Health National Cancer Institute.
483 citations
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TL;DR: The results show how social media may potentially be used to estimate real-time levels and changes in population-scale measures such as obesity rates.
Abstract: We conduct a detailed investigation of correlations between real-time expressions of individuals made across the United States and a wide range of emotional, geographic, demographic, and health characteristics. We do so by combining (1) a massive, geo-tagged data set comprising over 80 million words generated in 2011 on the social network service Twitter and (2) annually-surveyed characteristics of all 50 states and close to 400 urban populations. Among many results, we generate taxonomies of states and cities based on their similarities in word use; estimate the happiness levels of states and cities; correlate highly-resolved demographic characteristics with happiness levels; and connect word choice and message length with urban characteristics such as education levels and obesity rates. Our results show how social media may potentially be used to estimate real-time levels and changes in population-scale measures such as obesity rates.
483 citations
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TL;DR: The addition of exogenous IFNgamma during differentiation restores IL-12-mediated Th1 polarization in the JNK2-deficient mice and plays an important role in the balance of Th1 and Th2 immune responses.
482 citations
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TL;DR: In this article, the authors express the opinions of the individual evaluators regarding the strengths, weaknesses, and value of the books they review, as such the appraisals are subjective assessments and do not necessarily reflect the opinion of the editors or any official policy of the American Ornithologists' Union.
Abstract: Abstract The following critiques express the opinions of the individual evaluators regarding the strengths, weaknesses, and value of the books they review. As such, the appraisals are subjective assessments and do not necessarily reflect the opinions of the editors or any official policy of the American Ornithologists' Union.
481 citations
Authors
Showing all 17727 results
Name | H-index | Papers | Citations |
---|---|---|---|
Albert Hofman | 267 | 2530 | 321405 |
Ralph B. D'Agostino | 226 | 1287 | 229636 |
George Davey Smith | 224 | 2540 | 248373 |
Stephen V. Faraone | 188 | 1427 | 140298 |
Valentin Fuster | 179 | 1462 | 185164 |
Dennis J. Selkoe | 177 | 607 | 145825 |
Anders Björklund | 165 | 769 | 84268 |
Alfred L. Goldberg | 156 | 474 | 88296 |
Christopher P. Cannon | 151 | 1118 | 108906 |
Debbie A Lawlor | 147 | 1114 | 101123 |
Roger J. Davis | 147 | 498 | 103478 |
Andrew S. Levey | 144 | 600 | 156845 |
Jonathan G. Seidman | 137 | 563 | 89782 |
Yu Huang | 136 | 1492 | 89209 |
Christine E. Seidman | 134 | 519 | 67895 |