Learning from failure

We study decentralized learning in organizations. Decentralization is captured through a symmetry constraint on agents’ strategies. Among such attainable strategies, we solve for optimal and equilibrium strategies. We model the organization as a repeated game with imperfectly observable actions. A fixed but unknown subset of action profiles are successes and all other action profiles are failures. The game is played until either there is a success or the time horizon is reached. For any time horizon, including infinity, we demonstrate existence of optimal attainable strategies and show that they are Nash equilibria. For some time horizons, we can solve explicitly for the optimal attainable strategies and show uniqueness. The solution connects the learning behavior of agents to the fundamentals that characterize the organization: Agents in the organization respond more slowly to failure as the future becomes more important, the size of the organization increases and the probability of success decreases.Game theory

Mineralocorticoid receptor antagonism limits experimental choroidal neovascularization and structural changes associated with neovascular age-related macular degeneration.

Choroidal neovascularization (CNV) is a major cause of visual impairment in patients suffering from wet age-related macular degeneration (AMD), particularly when refractory to intraocular anti-VEGF injections. Here we report that treatment with the oral mineralocorticoid receptor (MR) antagonist spironolactone reduces signs of CNV in patients refractory to anti-VEGF treatment. In animal models of wet AMD, pharmacological inhibition of the MR pathway or endothelial-specific deletion of MR inhibits CNV through VEGF-independent mechanisms, in part through upregulation of the extracellular matrix protein decorin. Intravitreal injections of spironolactone-loaded microspheres and systemic delivery lead to similar reductions in CNV. Together, our work suggests MR inhibition as a novel therapeutic option for wet AMD patients unresponsive to anti-VEGF drugs

Switching between ranibizumab and aflibercept for the treatment of neovascular age-related macular degeneration.

The introduction of antivascular endothelial growth factor agents such as ranibizumab and aflibercept has revolutionized the management of neovascular age-related macular degeneration. A number of randomized clinical trials have shown that ranibizumab and aflibercept produce similar efficacy and safety outcomes. Most of the switching studies published to date show that efficacy benefits are uncontrolled, retrospective trials with limitations in terms of their selection, monitoring, numbers, and assessment criteria. Based on the published literature to date, we propose arguments for and against switching antivascular endothelial growth factor agents, provide our own perspective on this topic, and suggest a focus for future research

Tomographie a coherence optique dans la Malattia leventinese [Optical coherence tomography in Malattia Leventinese].

BACKGROUND: Malattia Leventinese (ML) is a genetically homogeneous macular dystrophy with an autosomal dominant mode of inheritance. Ophthalmoscopically it is recognisable by a radial pattern of drusen-like deposits in the macula and by parapapillary deposits, named Forni's verrucosities. The aim of this study is to describe optical coherence tomographic (OCT) findings and to compare them with histological data. PATIENTS AND METHODS: Six patients underwent ophthalmological examination, angiography and OCT. Diagnosis was confirmed by genetic analysis of the R345W mutation. A histopathological study of an ML donor eye was performed. RESULTS: OCT revealed a diffuse RPE-choriocapillaris thickening with nodular features in the macular and parapapillary areas. The protrusions reached as far as the outer nuclear layer. CONCLUSIONS: OCT is a non-invasive technique that provides a cross-sectional picture of the retina comparable to a histological section. In ML, OCT revealed a diffuse alteration of the RPE-Bruch's membrane complex. The macular and parapapillary nodular lesions are the tomographic equivalents of drusen and Forni's verrucosities