Expected utility within a generalized concept of probability — a comprehensive framework for decision making under ambiguity

Ambiguity, Interval probability, Decision Making, Expected Utility, Choquet Expected Utility, Imprecise Probabilities, Capacities, Lower and Upper Probabilities, Non-additive Measures, Belief Functions, Choquet Integral, Multiple Priors, Linear Programming, Ambiguity Aversion, Ambiguity Seeking,

Interface Contractility between Differently Fated Cells Drives Cell Elimination and Cyst Formation

Although cellular tumor-suppression mechanisms are widely studied, little is known about mechanisms that act at the level of tissues to suppress the occurrence of aberrant cells in epithelia. We find that ectopic expression of transcription factors that specify cell fates causes abnormal epithelial cysts in Drosophila imaginal discs. Cysts do not form cell autonomously but result from the juxtaposition of two cell populations with divergent fates. Juxtaposition of wild-type and aberrantly specified cells induces enrichment of actomyosin at their entire shared interface, both at adherens junctions as well as along basolateral interfaces. Experimental validation of 3D vertex model simulations demonstrates that enhanced interface contractility is sufficient to explain many morphogenetic behaviors, which depend on cell cluster size. These range from cyst formation by intermediate-sized clusters to segregation of large cell populations by formation of smooth boundaries or apical constriction in small groups of cells. In addition, we find that single cells experiencing lateral interface contractility are eliminated from tissues by apoptosis. Cysts, which disrupt epithelial continuity, form when elimination of single, aberrantly specified cells fails and cells proliferate to intermediate cell cluster sizes. Thus, increased interface contractility functions as error correction mechanism eliminating single aberrant cells from tissues, but failure leads to the formation of large, potentially disease-promoting cysts. Our results provide a novel perspective on morphogenetic mechanisms, which arise from cell-fate heterogeneities within tissues and maintain or disrupt epithelial homeostasis

Safety and Efficacy of a Flexible Dosing Regimen of Ranibizumab in Neovascular Age-Related Macular Degeneration: The SUSTAIN Study

Objective: To evaluate the safety and efficacy of individualized ranibizumab treatment in patients with neovascular age-related macular degeneration. Design: Twelve-month, phase III, multicenter, open-label, single-arm study. Participants: A total of 513 ranibizumab-naive SUSTAIN patients. Intervention: Three initial monthly injections of ranibizumab (0.3 mg) and thereafter pro re nata (PRN) retreatment for 9 months based on prespecified retreatment criteria. Patients switched to 0.5 mg ranibizumab after approval in Europe. Main Outcome Measures: Frequency of adverse events (AEs), monthly change of best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline, the time to first re-treatment, and the number of treatments were assessed. Results: A total of 249 patients (48.5%) reported ocular AEs, and 8 (1.5%) deaths, 5 (1.2%) patients with ocular serious AEs of the study eye (retinal hemorrhage, cataract, retinal pigment epithelial tear, reduced visual acuity [VA], vitreous hemorrhage), and 19 (3.7%) patients with arteriothromboembolic events were observed. Most frequent AEs in the study eye were reduced VA (18.5%), retinal hemorrhage (7.2%), increased intraocular pressure (7.0%), and conjunctival hemorrhage (5.5%). The average number of re-treatments from months 3 to 11 was 2.7. Mean best-corrected visual acuity increased steadily from baseline to month 3 to reach +5.8 letters, decreased slightly from month 3 to 6, and remained stable from month 6 to 12, reaching +3.6 at month 12. Mean change in CRT was -101.1 mu m from baseline to month 3 and -91.5 mu m from baseline to month 12. Conclusions: The safety results are comparable to the favorable tolerability profile of ranibizumab observed in previous pivotal clinical studies; individualized treatment with less than monthly re-treatments shows a similar safety profile as observed in previous randomized clinical trials with monthly ranibizumab treatment. Efficacy outcomes were achieved with a low average number of re-treatments. Visual acuity in SUSTAIN patients with individualized re-treatment based on VA/optical coherence tomography assessment reached on average a maximum after the first 3 monthly injections, decreased slightly under PRN during the next 2 to 3 months, and was then sustained throughout the treatment period. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2011; 118: 663-671 (C) 2011 by the American Academy of Ophthalmolog

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single-output = MISO) ermöglicht die Nutzung der räumlichen Dimension von Funkkanälen. Strahlformung fokussiert die Charakteristik einer Antennengruppe in eine bestimmte Richtung und erhöht dadurch die Signalleistung. Räumliche Diversität, die die Zuverlässigkeit einer Funkverbindung verbessert, entsteht durch räumliche Kopien des Funksignals. Durch den Einsatz einer zusätzlichen Antennengruppe am zweiten Ende der Funkverbindung (multipleinput multiple-output=MIMO) können mehrere Signalströme im räumlichen Multiplex-Verfahren parallel übertragen werden. Der erste Teil dieser Dissertation beschäftigt sich mit MISO-Kanälen. Da sich Signalgewinn durch Strahlformung und räumliche Diversität gegenseitig widersprechen, ist es wichtig eine optimale Balance zwischen diesen beiden Techniken zu finden. Die optimale Balance hängt sowohl von den Kanaleigenschaften und dem Wissen darüber ab, als auch von den Anforderungen an Datenrate und erlaubter Bitfehlerquote. Zum einen erläutere ich wieviel Gewinn durch Strahlformung und durch Diversität erreichbar ist, wenn man (i) nichts über den Kanal weiß, (ii) die Statistik zweiter Ordnung des Kanals kennt, oder (iii) vollständiges Kanalwissen vorliegt. Zum anderen konzentriere ich mich auf den Fall einer Antennengruppe bei einem Sender

Re: Dugel et al: HAWK and HARRIER: phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration (Ophthalmology. 2019 Apr 12 [Epub ahead of print]) Reply

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