Large-scale risks and technological change: What about limited liability?

We consider a firm that has to choose a technology to produce a given good. This technology drives a multiplicative large-scale risk of incident for Society: the total potential level of damage increases with the level of activity. Contrary to what is often argued in the literature, we show that limited liability can be more incentive for technical change than an unlimited liability rule, depending on the magnitude of the technological change and on the firm's size. In a second part of the paper, taxes are introduced. We show how manipulating the tax rate with respect to the technological choice made by the firm still enlarges the set of parameters that lead to technological change under a limited liability rule. Our normative results provide some arguments in favor of the limited liability rule, often considered as the main explanation of partial large-scale risk internalization by firms.Technological risk, limited liability, incentives, technical choice, taxes.

Gains in Power from Structured Two-Sample Tests of Means on Graphs

We consider multivariate two-sample tests of means, where the location shift between the two populations is expected to be related to a known graph structure. An important application of such tests is the detection of differentially expressed genes between two patient populations, as shifts in expression levels are expected to be coherent with the structure of graphs reflecting gene properties such as biological process, molecular function, regulation, or metabolism. For a fixed graph of interest, we demonstrate that accounting for graph structure can yield more powerful tests under the assumption of smooth distribution shift on the graph. We also investigate the identification of non-homogeneous subgraphs of a given large graph, which poses both computational and multiple testing problems. The relevance and benefits of the proposed approach are illustrated on synthetic data and on breast cancer gene expression data analyzed in context of KEGG pathways

Market Stability vs. Market Resilience: Regulatory Policies Experiments in an Agent-Based Model with Low- and High- Frequency Trading

We investigate the effects of different regulatory policies directed towards high-frequency trading (HFT) through an agent-based model of a limit order book able to generate flash crashes as the result of the interactions between low- and high-frequency (HF) traders. We analyze the impact of the imposition of minimum resting times, of circuit breakers (both ex-post and ex-ante types), of cancellation fees and of transaction taxes on asset price volatility and on the occurrence and duration of ash crashes. In the model, low- frequency agents adopt trading rules based on chronological time and can switch between fundamentalist and chartist strategies. In contrast, high-frequency traders activation is event-driven and depends on price fluctuations. In addition, high-frequency traders employ low-latency directional strategies that exploit market information and they can cancel their orders depending on expected profits. Monte-Carlo simulations reveal that reducing HF order cancellation, via minimum resting times or cancellation fees, or discouraging HFT via financial transaction taxes, reduces market volatility and the frequency of ash crashes. However, these policies also imply a longer duration of flash crashes. Furthermore, the introduction of an ex-ante circuit breaker markedly reduces price volatility and removes ash crashes. In contrast, ex-post circuit breakers do not affect market volatility and they increase the duration of flash crashes. Our results show that HFT-targeted policies face a trade-o between market stability and resilience. Policies that reduce volatility and the incidence of flash crashes also imply a reduced ability of the market to quickly recover from a crash. The dual role of HFT, as both a cause of the flash crash and a fundamental actor in the post-crash recovery underlies the above trade-off

Trading à haute fréquence et régulation économique, un arbitrage inéluctable entre stabilité et résilience des marchés financiers

Au cours des dernières décennies, le trading à haute fréquence (THF) a fortement augmenté sur les marchés américains et européens. Le THF représente un défi majeur pour les autorités de régulation du fait, d’une part, de la grande variété de stratégies de trading qu’il englobe (AFM, 2010 ; SEC, 2010) et d’autre part des incertitudes qui planent toujours autour des avantages nets de cette innovation financière pour les marchés financiers (Lattemann et al., 2012 ; ESMA, 2014 ; Aguilar, 2015). Par ailleurs, bien que le THF ait été identifié comme l’une des causes probables des krachs éclairs (Jacob Leal et al., 2016), aucun consensus n’a encore réellement émergé sur les causes fondamentales de ces phénomènes extrêmes. Certains pays ont déjà décidé de réguler le THF[*]. Cependant, les approches adoptées jusqu’à présent varient en fonction des régions. [Premier paragraphe

Incidence rate and risk factors for vaginal vault prolapse repair after hysterectomy

Our objective was to estimate the incidence and identify the risk factors for vaginal vault prolapse repair after hysterectomy. We conducted a case control study among 6,214 women who underwent hysterectomy from 1982 to 2002. Cases (n = 32) were women who required vaginal vault suspension following the hysterectomy through December 2005. Controls (n = 236) were women, randomly selected from the same cohort, who did not require pelvic organ prolapse surgery. The incidence of vaginal vault prolapse repair was 0.36 per 1,000 women-years. The cumulative incidence was 0.5%. Risk factors included preoperative prolapse (odds ratio (OR) 6.6; 95% confidence interval (CI) 1.5-28.4) and sexual activity (OR 1.3; 95% CI 1.0-1.5). Vaginal hysterectomy was not a risk factor when preoperative prolapse was taken into account (OR 0.9; 95% CI 0.5-1.8).Vaginal vault prolapse repair after hysterectomy is an infrequent event and is due to preexisting weakness of pelvic tissue

USING ESDM 12 HOURS PER WEEK IN CHILDREN WITH AUTISM SPECTRUM DISORDER: FEASIBILITY AND RESULTS OF AN OBSERVATIONAL STUDY

Background: Early intervention for Autism Spectrum Disorder (ASD) in France is heterogeneous and poorly evaluated to date. Early Start Denver Model (ESDM) is a developmental and behavioral model ofintervention for toddlers with ASD which has already shown very interesting outcomes on the development of children with ASD in various studies with different settings. However, it is not possible with the current research to agree on the best setting. Thus, we implemented an ESDM program according to our context where children are often pre-schooling early from 30 months old. This therapy was applied by a multidisciplinary team working in close collaboration with parents and other partners. Subjects and methods: A prospective observational study including 19 toddlers with ASD was conducted. We evaluated improvement on the cognitive level of toddlers with ASD receiving therapist-delivered ESDM intervention for 12 hours per week. Results: Significant improvements in verbal and nonverbal cognitive skills at the Mullen Scale of Early Learning were obtained after 10 months of intervention in our sample. The largest improvement was in receptive language development quotient with a mean improvement of 19.6 points. We also observed promising outcomes in daily adaptive behavior, with a slight improvement in communication at the Vineland Adaptive Behavioral Scale. These outcomes, when compared to the conclusions of previous studies, are leading us to the need for a therapy duration beyond 10 months. Conclusions: Our outcomes were very encouraging even with lowcognitive and nonverbal children. These outcomes may be confirmed in a multicenter randomized controlled trial that is ongoing

The Signal Peptide of Staphylococcus aureus Panton Valentine Leukocidin LukS Component Mediates Increased Adhesion to Heparan Sulfates

Staphylococcus aureus necrotizing pneumonia is a severe disease caused by S. aureus strains carrying the Panton Valentine leukocidin (PVL) genes (lukS-PV & lukF-PV) encoded on various bacteriophages (such as phiSLT). Clinical PVL+ strains isolated from necrotizing pneumonia display an increased attachment to matrix molecules (type I and IV collagens and laminin), a phenotype that could play a role in bacterial adhesion to damaged airway epithelium during the early stages of necrotizing pneumonia (J Infect Dis 2004; 190: 1506–15). To investigate the basis of the observed adhesion of S. aureus PVL+ strains, we compared the ability of PVL+ and their isogenic PVL− strains to attach to various immobilized matrix molecules. The expression of recombinant fragments of the PVL subunits and the addition of synthetic peptides indicated that the processed LukS-PV signal peptide (LukS-PV SP) was sufficient to significantly enhance the ability of S. aureus to attach to extracellular matrix (ECM) components. Furthermore, we showed that adhesion to ECM components was inhibited by heparin and heparan sulfates (HS) suggesting that in vivo, HS could function as a molecular bridge between the matrix and S. aureus expressing the LukS-PV signal peptide. Site directed mutagenesis, biochemical and structural analyses of the LukS-PV signal peptide indicate that this peptide is present at the S. aureus surface, binds to HS in solid phase assay, and mediates the enhanced S. aureus matrix component adhesion. Our data suggests that after its cleavage by signal peptidase, the signal peptide is released from the membrane and associates to the cell wall through its unique C-terminus sequence, while its highly positively charged N-terminus is exposed on the bacterial surface, allowing its interaction with extracellular matrix-associated HS. This mechanism may provide a molecular bridge that enhances the attachment of the S. aureus PVL+ strains to ECM components exposed at damaged epithelial sites

GluN2A NMDA Receptor Enhancement Improves Brain Oscillations, Synchrony, and Cognitive Functions in Dravet Syndrome and Alzheimer's Disease Models.

NMDA receptors (NMDARs) play subunit-specific roles in synaptic function and are implicated in neuropsychiatric and neurodegenerative disorders. However, the in vivo consequences and therapeutic potential of pharmacologically enhancing NMDAR function via allosteric modulation are largely unknown. We examine the in vivo effects of GNE-0723, a positive allosteric modulator of GluN2A-subunit-containing NMDARs, on brain network and cognitive functions in mouse models of Dravet syndrome (DS) and Alzheimer's disease (AD). GNE-0723 use dependently potentiates synaptic NMDA receptor currents and reduces brain oscillation power with a predominant effect on low-frequency (12-20 Hz) oscillations. Interestingly, DS and AD mouse models display aberrant low-frequency oscillatory power that is tightly correlated with network hypersynchrony. GNE-0723 treatment reduces aberrant low-frequency oscillations and epileptiform discharges and improves cognitive functions in DS and AD mouse models. GluN2A-subunit-containing NMDAR enhancers may have therapeutic benefits in brain disorders with network hypersynchrony and cognitive impairments

Molecular Insights into an Antibiotic Enhancer Action of New Morpholine-Containing 5-Arylideneimidazolones in the Fight against MDR Bacteria

In the search for an effective strategy to overcome antimicrobial resistance, a series of new morpholine-containing 5-arylideneimidazolones differing within either the amine moiety or at position five of imidazolones was explored as potential antibiotic adjuvants against Gram-positive and Gram-negative bacteria. Compounds (7–23) were tested for oxacillin adjuvant properties in the Methicillin-susceptible S. aureus (MSSA) strain ATCC 25923 and Methicillin-resistant S. aureus MRSA 19449. Compounds 14–16 were tested additionally in combination with various antibiotics. Molecular modelling was performed to assess potential mechanism of action. Microdilution and real-time efflux (RTE) assays were carried out in strains of K. aerogenes to determine the potential of compounds 7–23 to block the multidrug efflux pump AcrAB-TolC. Drug-like properties were determined experimentally. Two compounds (10, 15) containing non-condensed aromatic rings, significantly reduced oxacillin MICs in MRSA 19449, while 15 additionally enhanced the effectiveness of ampicillin. Results of molecular modelling confirmed the interaction with the allosteric site of PBP2a as a probable MDR-reversing mechanism. In RTE, the compounds inhibited AcrAB-TolC even to 90% (19). The 4-phenylbenzylidene derivative (15) demonstrated significant MDR-reversal “dual action” for β-lactam antibiotics in MRSA and inhibited AcrAB-TolC in K. aerogenes. 15 displayed also satisfied solubility and safety towards CYP3A4 in vitro

Automated data processing architecture for the Gemini Planet Imager Exoplanet Survey

The Gemini Planet Imager Exoplanet Survey (GPIES) is a multi-year direct imaging survey of 600 stars to discover and characterize young Jovian exoplanets and their environments. We have developed an automated data architecture to process and index all data related to the survey uniformly. An automated and flexible data processing framework, which we term the Data Cruncher, combines multiple data reduction pipelines together to process all spectroscopic, polarimetric, and calibration data taken with GPIES. With no human intervention, fully reduced and calibrated data products are available less than an hour after the data are taken to expedite follow-up on potential objects of interest. The Data Cruncher can run on a supercomputer to reprocess all GPIES data in a single day as improvements are made to our data reduction pipelines. A backend MySQL database indexes all files, which are synced to the cloud, and a front-end web server allows for easy browsing of all files associated with GPIES. To help observers, quicklook displays show reduced data as they are processed in real-time, and chatbots on Slack post observing information as well as reduced data products. Together, the GPIES automated data processing architecture reduces our workload, provides real-time data reduction, optimizes our observing strategy, and maintains a homogeneously reduced dataset to study planet occurrence and instrument performance.Comment: 21 pages, 3 figures, accepted in JATI