When Does Libertarian Paternalism Work?

We develop a theoretical model to study the effects of libertarian paternalism on knowledge acquisition and social learning. Individuals in our model are permitted to appreciate and use the information content in the default options set by the government. We show that in some settings libertarian paternalism may decrease welfare because default options slow information aggregation in the market. We also analyze what happens when the government acquires imprecise information about individuals, and characterize its incentives to avoid full disclosure of its information to the market, even when it has perfect information. Finally, we consider a market in which individuals can sell their information to others and show that the presence of default options causes the quality of advice to decrease, which may lower social welfare.

Shallow Dark Matter Cusps in Galaxy Clusters

We study the evolution of the stellar and dark matter components in a galaxy cluster of $10^{15} \, \rm{M_{\odot}}$ from $z=3$ to the present epoch using the high-resolution collisionless simulations of Ruszkowski & Springel (2009). At $z=3$ the dominant progenitor halos were populated with spherical model galaxies with and without accounting for adiabatic contraction. We apply a weighting scheme which allows us to change the relative amount of dark and stellar material assigned to each simulation particle in order to produce luminous properties which agree better with abundance matching arguments and observed bulge sizes at $z=3$. This permits the study of the effect of initial compactness on the evolution of the mass-size relation. We find that for more compact initial stellar distributions the size of the final Brightest Cluster Galaxy grows with mass according to $r\propto M^{2}$, whereas for more extended initial distributions, $r\propto M$. Our results show that collisionless mergers in a cosmological context can reduce the strength of inner dark matter cusps with changes in logarithmic slope of 0.3 to 0.5 at fixed radius. Shallow cusps such as those found recently in several strong lensing clusters thus do not necessarily conflict with CDM, but may rather reflect on the initial structure of the progenitor galaxies, which was shaped at high redshift by their formation process.Comment: 8 pages, 4 figures, submitted to MNRA

Experimental Demonstration of Extended 5G Digital Fronthaul Over a Partially-Disaggregated WDM/SDM Network

© 2021 IEEE. Personal use of this material is permitted. Permissíon from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertisíng or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.[EN] We experimentally demonstrate a 5G digital fronthaul network that relies on multi-adaptive bandwidth/bitrate variable transceivers (BVTs) and an autonomic software-defined networking (SDN) control system for partially-disaggregated wavelength division multiplexing (WDM)/space division multiplexing (SDM). Transmission of 256-QAM 760.32 MHz orthogonal frequency-division multiplexing (OFDM) radio signal is performed, with a total radio transmission capacity of 5.667 Gb/s. Digitized signal samples are carried as a 22.25 Gb/s digitized radio-over-fiber (DRoF) data stream and transmitted over a WDM/SDM infrastructure including 40-wavelength 100-GHz arrayed waveguide gratings (AWGs) and 19-core fiber. The autonomic SDN controller deploys a control loop for the multi-adaptive OFDM-based BVTs that monitors the per-subcarrier signal to noise ratio (SNR) and assigns the optimal constellation based on the actual signal degradation. An error vector magnitude (EVM) below the targeted 2.1% is achieved while setting up connections in less than 5 s.This work was supported in part by the EC H2020 BLUESPACE Project under Grant 762055 and in part by the Spanish MICINN AURORAS Project under Grant RTI2018-099178.Fabrega, JM.; Múñoz, R.; Nadal, L.; Manso, C.; Svaluto Moreolo, M.; Vilalta, R.; Martínez, R.... (2021). Experimental Demonstration of Extended 5G Digital Fronthaul Over a Partially-Disaggregated WDM/SDM Network. IEEE Journal on Selected Areas in Communications. 39(9):2804-2815. https://doi.org/10.1109/JSAC.2021.3064645S2804281539

Concordance between CA-125 and RECIST progression in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer treated in the SOLO2 trial with olaparib as maintenance therapy after response to chemotherapy

BACKGROUND: Limited evidence exists to support CA-125 as a valid surrogate biomarker for progression in patients with ovarian cancer on maintenance PARP inhibitor (PARPi) therapy. We aimed to assess the concordance between CA-125 and Response Evaluation Criteria in Solid Tumours (RECIST) criteria for progression in patients with BRCA mutations on maintenance PARPi or placebo. METHODS: We extracted data on progression as defined by Gynecologic Cancer InterGroup CA-125, investigator- and independent central-assessed RECIST from the SOLO2/ENGOT-ov21(NCT01874353) trial. We excluded those with progression other than by RECIST, progression on date of randomisation, and no repeat CA-125 beyond baseline. We evaluated the concordance between CA-125 progression and RECIST progression, and assessed the negative (NPV) and positive predictive value (PPV). RESULTS: Of 295 randomised patients, 275 (184 olaparib, 91 placebo) were included. 171 patients had investigator-assessed RECIST progression. Of 80 patients with CA-125 progression, 77 had concordant RECIST progression (PPV 96%, 95% confidence interval 90-99%). Of 195 patients without CA-125 progression, 94 had RECIST progression (NPV 52%, 45-59%). Within treatment arms, PPV was similar (olaparib: 95% [84-99%], placebo: 97% [87-100%]) but NPV was lower in patients on placebo (olaparib: 60% [52-68%], placebo: 30% [20-44%]). Of 94 patients with RECIST but without CA-125 progression, 64 (68%) had CA-125 that remained within normal range. We observed similar findings using independent-assessed RECIST. CONCLUSIONS: Almost half the patients without CA-125 progression had RECIST progression, and most of these had CA-125 within the normal range. Regular computed tomography imaging should be considered as part of surveillance in patients treated with or without maintenance olaparib rather than relying on CA-125 alone

Critically short telomeres and toxicity of chemotherapy in early breast cancer

Cumulative toxicity from weekly paclitaxel (myalgia, peripheral neuropathy, fatigue) compromises long-term administration. Preclinical data suggest that the burden of critically short telomeres ( 21.9% CSTs) had 2-fold higher number of neuropathy (P = 0.04) or fatigue (P = 0.019) episodes and >3-fold higher number of myalgia episodes (P = 0.005). The average telomere length was unrelated to the incidence of side effects.The percentage of CSTs, but not the average telomere size, is associated with weekly paclitaxel-derived toxicity.This work was supported by the Fondo de Investigación Sanitaria [FIS PI10/00288 and FIS PI13/00430]; AECC Scientific Foundation [Beca de Retorno-2010, to MQF]; Spanish Ministry of Economy and Competitiveness Projects [SAF2013-45111-R]; Madrid Regional Government Projects [S2010/BMD- 2303]; AXA Research Found; Fundación Botin; AVON Spain; and Boehringer-Ingelheim Spain.S

The role of Zn-OR and Zn-OH nucleophiles and the influence of para-substituents in the reactions of binuclear phosphatase mimetics

Analogues of the ligand 2,2'-(2-hydroxy-5-methyl-1,3-phenylene)bis(methylene)bis((pyridin-2-ylmethyl)azanediyl)diethanol (CH(3)H(3)L1) are described. Complexation of these analogues, 2,6-bis(((2-methoxyethyl)(pyridin-2-ylmethyl)amino)methyl)-4-methylphenol (CH(3)HL2), 4-bromo-2,6-bis(((2-methoxyethyl)(pyridin-2-ylmethyl)amino)methyl)phenol (BrHL2), 2,6-bis(((2-methoxyethyl)(pyridin-2-ylmethyl)amino)methyl)-4-nitrophenol (NO(2)HL2) and 4-methyl-2,6-bis(((2-phenoxyethyl)(pyridin-2-ylmethyl)amino)methyl)phenol (CH(3)HL3) with zinc(II) acetate afforded [Zn-2(CH(3)L2)(CH3COO)(2)](PF6), [Zn-2(NO(2)L2)(CH3COO)(2)](PF6), [Zn-2(BrL2)(CH3COO)(2)](PF6) and [Zn-2(CH(3)L3)(CH3COO)(2)](PF6), in addition to [Zn-4(CH(3)L2)(2)(NO2C6H5OPO3)(2)(H2O)(2)](PF6)(2) and [Zn-4(BrL2)(2)(PO3F)(2)(H2O)(2)](PF6)(2). The complexes were characterized using H-1 and C-13 NMR spectroscopy, mass spectrometry, microanalysis, and X-ray crystallography. The complexes contain either a coordinated methyl-(L2 ligands) or phenyl-(L3 ligand) ether, replacing the potentially nucleophilic coordinated alcohol in the previously reported complex [Zn-2(CH(3)HL1)(CH3COO)(H2O)](PF6). Functional studies of the zinc complexes with the substrate bis(2,4-dinitrophenyl) phosphate (BDNPP) showed them to be competent catalysts with, for example, [Zn-2(CH(3)L2)](+), k(cat) = 5.70 +/- 0.04 x 10(-3) s(-1) (K-m = 20.8 +/- 5.0 mM) and [Zn-2(CH(3)L3)](+), kcat = 3.60 +/- 0.04 x 10(-3) s(-1) (K-m = 18.9 +/- 3.5 mM). Catalytically relevant pK(a)s of 6.7 and 7.7 were observed for the zinc(II) complexes of CH(3)L2(-) and CH(3)L3(-), respectively. Electron donating para-substituents enhance the rate of hydrolysis of BDNPP such that k(cat) p-CH3 > p-Br > p-NO2. Use of a solvent mixture containing H2O18/H2O16 in the reaction with BDNPP showed that for [Zn-2(CH(3)L2)(CH3COO)(2)](PF6) and [Zn-2(NO(2)L2)(CH3COO)(2)](PF6), as well as [Zn-2(CH(3)HL1)(CH3COO)(H2O)](PF6), the O-18 label was incorporated in the product of the hydrolysis suggesting that the nucleophile involved in the hydrolysis reaction was a Zn-OH moiety. The results are discussed with respect to the potential nucleophilic species (coordinated deprotonated alcohol versus coordinated hydroxide)

Staphylococcus aureus infection dynamics

Staphylococcus aureus is a human commensal that can also cause systemic infections. This transition requires evasion of the immune response and the ability to exploit different niches within the host. However, the disease mechanisms and the dominant immune mediators against infection are poorly understood. Previously it has been shown that the infecting S. aureus population goes through a population bottleneck, from which very few bacteria escape to establish the abscesses that are characteristic of many infections. Here we examine the host factors underlying the population bottleneck and subsequent clonal expansion in S. aureus infection models, to identify underpinning principles of infection. The bottleneck is a common feature between models and is independent of S. aureus strain. Interestingly, the high doses of S. aureus required for the widely used "survival" model results in a reduced population bottleneck, suggesting that host defences have been simply overloaded. This brings into question the applicability of the survival model. Depletion of immune mediators revealed key breakpoints and the dynamics of systemic infection. Loss of macrophages, including the liver Kupffer cells, led to increased sensitivity to infection as expected but also loss of the population bottleneck and the spread to other organs still occurred. Conversely, neutrophil depletion led to greater susceptibility to disease but with a concomitant maintenance of the bottleneck and lack of systemic spread. We also used a novel microscopy approach to examine abscess architecture and distribution within organs. From these observations we developed a conceptual model for S. aureus disease from initial infection to mature abscess. This work highlights the need to understand the complexities of the infectious process to be able to assign functions for host and bacterial components, and why S. aureus disease requires a seemingly high infectious dose and how interventions such as a vaccine may be more rationally developed

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe