2 results
Everolimus for cardiac rhabdomyomas in children with tuberous sclerosis. The ORACLE study protocol (everOlimus for caRdiac rhAbdomyomas in tuberous sCLErosis): a randomised, multicentre, placebo-controlled, double-blind phase II trial
- Erica V. Stelmaszewski, Daniella B. Parente, Alberto Farina, Anna Stein, Anthony Gutierrez, Antonio F. Raquelo-Menegassio, Carla Manterola, Carolina F. de Sousa, Carolina Victor, Dina Maki, Elias M. Morón, Fabiano F. de Abrantes, Fatima Iqbal, Jazmin Camacho-Vilchez, Joanna Jimenez-Pavón, Juan P. Polania, Lorenzo Thompson, Lygia Bonanato, Matthias Diebold, Maria V. C. P. Da Silva, Mariam W. J. Nashwan, Marianna A. G. Galvani, Osama E. A. Idris, Pierina Danos, Rocio Ortiz-Lopez, Rofida A. A. Mahmoud, Sergio Gresse, Jr, Karla L. Loss
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- Journal:
- Cardiology in the Young / Volume 30 / Issue 3 / March 2020
- Published online by Cambridge University Press:
- 27 January 2020, pp. 337-345
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- Article
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Introduction:
Tuberous sclerosis complex is a rare genetic disorder leading to the growth of hamartomas in multiple organs, including cardiac rhabdomyomas. Children with symptomatic cardiac rhabdomyoma require frequent admissions to intensive care units, have major complications, namely, arrhythmias, cardiac outflow tract obstruction and heart failure, affecting the quality of life and taking on high healthcare cost. Currently, there is no standard pharmacological treatment for this condition, and the management includes a conservative approach and supportive care. Everolimus has shown positive effects on subependymal giant cell astrocytomas, renal angiomyolipoma and refractory seizures associated with tuberous sclerosis complex. However, evidence supporting efficacy in symptomatic cardiac rhabdomyoma is limited to case reports. The ORACLE trial is the first randomised clinical trial assessing the efficacy of everolimus as a specific therapy for symptomatic cardiac rhabdomyoma.
Methods:ORACLE is a phase II, prospective, randomised, placebo-controlled, double-blind, multicentre protocol trial. A total of 40 children with symptomatic cardiac rhabdomyoma secondary to tuberous sclerosis complex will be randomised to receive oral everolimus or placebo for 3 months. The primary outcome is 50% or more reduction in the tumour size related to baseline. As secondary outcomes we include the presence of arrhythmias, pericardial effusion, intracardiac obstruction, adverse events, progression of tumour reduction and effect on heart failure.
Conclusions:ORACLE protocol addresses a relevant unmet need in children with tuberous sclerosis complex and cardiac rhabdomyoma. The results of the trial will potentially support the first evidence-based therapy for this condition.
6 - Rabbinic Interpretation
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- By Dina Stein
- Edited by Ronald Hendel, University of California, Berkeley
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- Book:
- Reading Genesis
- Published online:
- 05 June 2012
- Print publication:
- 27 September 2010, pp 119-135
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- Chapter
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Summary
Midrash and its precursors
Rabbinic interpretations of Scripture – unlike the creation of the world (at least according to some ancient exegetes) – were not a creation ex nihilo. They were preceded by a long and varied chain of tradition that, in turn, was adapted by the rabbis to suit their own cultural needs. To fully appreciate the rabbinic exegetical enterprise, we must pay attention to the legacy (at times hidden) that informed their practice and, at the same time, recognize the astonishing novelty of their project. The novelty lies not only in the thematic plan but also, as I argue, predominantly in the formal–rhetorical aspect of their writings. That is, what we see in rabbinic interpretation of Scripture is a new epistemology, one that situates the text itself as an explicit locus of knowledge. This epistemological shift is implicated in the self-reflexive character of rabbinic texts themselves, which in turn render the characters they embody – whether they are the projected biblical protagonists or the implied rabbinic subjects – self-reflective. Before addressing this epistemological shift, we must first turn to the beginning.
The book of Genesis begins with a seemingly simple, although grammatically awkward, statement: “In the beginning God created heaven and earth.” Yet, already in Scripture itself we find that imagining the very moment of creation did not end (nor did it begin) in Genesis 1. When Wisdom, the speaker in Proverbs 8, announces, “The Lord made me the beginning of his course, the first of his acts of old” (8:22), it inscribes itself as a transformative force in the primordial moment. Here and elsewhere, the first traces of the retelling of the Genesis story are to be found within the Bible. Whether imagined in the conceptual framework of Sophia-Ḥokmah (as in Proverbs), or as God's battle with mythological beasts (as in Psalms or Job), or in the creation language of the building of the tabernacle (as in Exodus), these texts tell a different story than the one told in the opening chapter of the canon. Not only do mythological beasts – conspicuously absent from the Genesis Creation narrative (albeit etymologically alluded to in the name Tehom/Tiamat) – resurface in other texts, but also the universalistic paradigm that the Genesis story outlines is later linked to a particularistic trajectory concerning Israel and its redemption from Egypt. Competing or reworked traditions, and even exegesis of Genesis narratives, are contained within Scripture itself, attesting to the different schools and the long process that informed its formation until it reached the final stage of canonization sometime in the first century C.E.
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