| 1. |
- Cicardi, M., et al.
(author)
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Icatibant, a New Bradykinin-Receptor Antagonist, in Hereditary Angioedema
- 2010
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In: New England Journal of Medicine. - 0028-4793. ; 363:6, s. 532-541
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Journal article (peer-reviewed)abstract
- BACKGROUND Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist. METHODS In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms. RESULTS A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported. CONCLUSIONS In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)
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| 2. |
- Trigueiro Baptista, Arthur, et al.
(author)
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Towards an uncertainty aware short-term travel time prediction using GPS bus data : Case study in Dublin
- 2012
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In: Intelligent Transportation Systems (ITSC), 2012 15th International IEEE Conference on. - : IEEE. - 9781467330640 ; , s. 1620-1625
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Conference paper (peer-reviewed)abstract
- In this paper we propose and study the performances of a bus travel times prediction model using real bus location data from the city of Dublin. The proposed prediction model uses a modified version of the K-Nearest Neighbors algorithm, KNN, algorithm and exhibits a significant improvement over the baseline KNN. We also investigate the benefits of decomposing travel times in three components: running time, dwell time at bus stops and time stopped at traffic lights. We discuss that most of the uncertainty on the travel times comes from time spent at bus stops and traffic lights, and prediction of running time only is much improved due to the reduced uncertainty at bus stops and traffic lights. Finally we show the need of a prediction algorithm for time spent at bus stops and traffic lights that added to the prediction of running time would allow for an uncertainty aware travel time predictor.
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| 3. |
- Kelly, GL, et al.
(author)
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Targeting of MCL-1 kills MYC-driven mouse and human lymphomas even when they bear mutations in p53
- 2014
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In: Genes & development. - : Cold Spring Harbor Laboratory. - 1549-5477 .- 0890-9369. ; 28:1, s. 58-70
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Journal article (peer-reviewed)abstract
- The transcriptional regulator c-MYC is abnormally overexpressed in many human cancers. Evasion from apoptosis is critical for cancer development, particularly c-MYC-driven cancers. We explored which anti-apoptotic BCL-2 family member (expressed under endogenous regulation) is essential to sustain c-MYC-driven lymphoma growth to reveal which should be targeted for cancer therapy. Remarkably, inducible Cre-mediated deletion of even a single Mcl-1 allele substantially impaired the growth of c-MYC-driven mouse lymphomas. Mutations in p53 could diminish but not obviate the dependency of c-MYC-driven mouse lymphomas on MCL-1. Importantly, targeting of MCL-1 killed c-MYC-driven human Burkitt lymphoma cells, even those bearing mutations in p53. Given that loss of one allele of Mcl-1 is well tolerated in healthy tissues, our results suggest that therapeutic targeting of MCL-1 would be an attractive therapeutic strategy for MYC-driven cancers.
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