Robustness and Infrared Sensitivity of Various Observables in the Application of AdS/CFT to Heavy Ion Collisions

We investigate the robustness with respect to nonconformality of five properties of strongly coupled plasmas that have been calculated in N=4 supersymmetric Yang-Mills (SYM) theory at nonzero temperature, motivated by the goal of understanding phenomena in heavy ion collisions. (The properties are the jet quenching parameter, the velocity dependence of screening, and the drag and transverse and longitudinal momentum diffusion coefficients for a heavy quark pulled through the plasma.) We use a toy model in which nonconformality is introduced via a one-parameter deformation of the AdS black hole dual to the hot N=4 SYM plasma. Upon introducing a degree of nonconformality comparable to that seen in lattice calculations of QCD at temperatures a few times that of the crossover to quark-gluon plasma, we find that the jet quenching parameter is affected by the nonconformality by at most 30%, the screening length is affected by at most 20%, but the drag and diffusion coefficients for a slowly moving heavy quark can be modified by as much as 80%. However, four of the five properties that we investigate become completely insensitive to the nonconformality in the limit v -> 1. The exception is the jet quenching parameter, which is "infrared sensitive" even at v=1, where it is defined. It is the only high-velocity observable that we investigate which is sensitive to properties of the medium at infrared energy scales proportional to T, namely the scales where the quark-gluon plasma of QCD can be strongly coupled. The other four quantities all probe only scales that are larger than T by a factor that diverges as v -> 1, namely scales where the N=4 SYM plasma can be strongly coupled but the quark-gluon plasma of QCD is not.Comment: Minor revisions, including expansion of Footnote 4. Version to appear in JHEP. 36 pages, 5 figure

Distributed Adaptive Gradient Algorithm with Gradient Tracking for Stochastic Non-Convex Optimization

This paper considers a distributed stochastic non-convex optimization problem, where the nodes in a network cooperatively minimize a sum of $L$-smooth local cost functions with sparse gradients. By adaptively adjusting the stepsizes according to the historical (possibly sparse) gradients, a distributed adaptive gradient algorithm is proposed, in which a gradient tracking estimator is used to handle the heterogeneity between different local cost functions. We establish an upper bound on the optimality gap, which indicates that our proposed algorithm can reach a first-order stationary solution dependent on the upper bound on the variance of the stochastic gradients. Finally, numerical examples are presented to illustrate the effectiveness of the algorithm.Comment: 14 pages, 8 figure

A missense mutation in Pitx2 leads to early-onset glaucoma via NRF2-YAP1 axis.

Glaucoma is a leading cause of blindness, affecting 70 million people worldwide. Owing to the similarity in anatomy and physiology between human and mouse eyes and the ability to genetically manipulate mice, mouse models are an invaluable resource for studying mechanisms underlying disease phenotypes and for developing therapeutic strategies. Here, we report the discovery of a new mouse model of early-onset glaucoma that bears a transversion substitution c. G344T, which results in a missense mutation, p. R115L in PITX2. The mutation causes an elevation in intraocular pressure (IOP) and progressive death of retinal ganglion cells (RGC). These ocular phenotypes recapitulate features of pathologies observed in human glaucoma. Increased oxidative stress was evident in the inner retina. We demonstrate that the mutant PITX2 protein was not capable of binding to Nuclear factor-like 2 (NRF2), which regulates Pitx2 expression and nuclear localization, and to YAP1, which is necessary for co-initiation of transcription of downstream targets. PITX2-mediated transcription of several antioxidant genes were also impaired. Treatment with N-Acetyl-L-cysteine exerted a profound neuroprotective effect on glaucoma-associated neuropathies, presumably through inhibition of oxidative stress. Our study demonstrates that a disruption of PITX2 leads to glaucoma optic pathogenesis and provides a novel early-onset glaucoma model that will enable elucidation of mechanisms underlying the disease as well as to serve as a resource to test new therapeutic strategies

Evaluation of the efficacy and safety of intravenous remdesivir in adult patients with severe COVID-19: study protocol for a phase 3 randomized, double-blind, placebo-controlled, multicentre trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by a novel corinavirus (later named SARS-CoV-2 virus), was fistly reported in Wuhan, Hubei Province, China towards the end of 2019. Large-scale spread within China and internationally led the World Health Organization to declare a Public Health Emergency of International Concern on 30th January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure, and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including MERS-CoV and SARS-CoV, in in vitro and in vivo experiments. It is also inhibitory against the COVID-19 virus in vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe COVID-19. METHODS: The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (≥ 18 years) with laboratory-confirmed COVID-19 virus infection, severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenously administered remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 = discharged; 6 = death) or live discharge from hospital. One interim analysis for efficacy and futility will be conducted once half of the total number of events required has been observed. DISCUSSION: This is the first randomized, placebo-controlled trial in COVID-19. Enrolment began in sites in Wuhan, Hubei Province, China on 6th February 2020. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04257656. Registered on 6 February 2020

Brain-wide functional connectivity alterations and their cognitive correlates in subjective cognitive decline

BackgroundIndividuals with subjective cognitive decline (SCD) are at risk of developing Alzheimer's Disease (AD). Traditional seed-based analysis has shown biased functional connectivity (FC) in SCD individuals. To investigate unbiased altered FC by the brain-wide association study (BWAS) and to determine its association with cognition in SCD individuals.MethodsMeasure of association (MA) analysis was applied to detect significant voxels with FC changes. Based on these changes, we identified regions of interest (ROIs) and conducted ROI-wise FC analyses. Correlation analyses were then performed between these FC circuits and cognition.ResultsMA analysis identified 10 ROIs with significantly altered voxels. ROI-wise FC analyses revealed 14 strengthened FC, predominantly parietal-occipital link alterations. The FC between the right superior occipital gyrus and the right postcentral gyrus correlated positively with executive function, while the FC between the right middle occipital gyrus and the left angular gyrus correlated positively with episodic memory in SCD individuals.ConclusionSCD involves multifocal impairments, of which regions of default mode network (DMN) and occipital lobe should be specially focused. Cross-hemispheric alterations indicate an internal interactive impairment pattern in SCD. The reduced FC between the right superior occipital gyrus and the right postcentral gyrus, and between the right middle occipital gyrus and the left angular gyrus, which correlate with specific cognitive functions, could serve as potential biomarkers for SCD diagnosis

Prospective evaluation of a rapid clinical metagenomics test for bacterial pneumonia

Background: The diagnosis of bacterial pathogens in lower respiratory tract infections (LRI) using conventional culture methods remains challenging and time-consuming.  Objectives: To evaluate the clinical performance of a rapid nanopore-sequencing based metagenomics test for diagnosis of bacterial pathogens in common LRIs through a large-scale prospective study.  Methods: We enrolled 292 hospitalized patients suspected to have LRIs between November 2018 and June 2019 in a single-center, prospective cohort study. Rapid clinical metagenomics test was performed on-site, and the results were compared with those of routine microbiology tests.  Results: 171 bronchoalveolar lavage fluid (BAL) and 121 sputum samples were collected from patients with six kinds of LRIs. The turnaround time (from sample registration to result) for the rapid metagenomics test was 6.4 ± 1.4 hours, compared to 94.8 ± 34.9 hours for routine culture. Compared with culture and real-time PCR validation tests, rapid metagenomics achieved 96.6% sensitivity and 88.0% specificity and identified pathogens in 63 out of 161 (39.1%) culture-negative samples. Correlation between enriched anaerobes and lung abscess was observed by Gene Set Enrichment Analysis. Moreover, 38 anaerobic species failed in culture was identified by metagenomics sequencing. The hypothetical impact of metagenomics test proposed antibiotic de-escalation in 34 patients compared to 1 using routine culture.  Conclusions: Rapid clinical metagenomics test improved pathogen detection yield in the diagnosis of LRI. Empirical antimicrobial therapy could be de-escalated if rapid metagenomics test results were hypothetically applied to clinical management

When to increase firms’ sustainable operations for efficiency? A data envelopment analysis in the retailing industry

International audienceRetailers increasingly incorporate sustainable operations to improve their efficiency, which raises questions: Is it always beneficial to increase firms’ sustainable operations for operational efficiency? Under which conditions should a retailer increase its socially-responsible and environmentally-friendly operations to improve efficiency? Our research addresses inconsistent viewpoints in relation to sustainable activities and performance at an operational level, and fills in research gaps in measuring the efficiency of, and identifying the operational mechanisms active in, sustainable retail operations. By collecting data from 124 retailers, we integrate the DEA (data envelopment analysis) model with empirical methods. We first apply DEA models to evaluate the efficiency of retailers. Using efficiency values provided by DEA, we conduct hierarchical regression analysis to examine the influence of socially-responsible and environmentally-friendly operations, and understand the role of sustainable operations in the supply chain. Finally, we use nonlinear analysis to identify the conditions required to increase the efficiency of sustainable operations. Supply chain integration can improve efficiency with higher levels of socio-economic integration and environmental-economic integration. Firms in an internal operational environment with a higher level of financial flow integration and a lower level of physical flow integration are more likely to achieve high retail efficiency.We find two conditions for implementation with managerial insights. When these conditions, characterized by financial flow and physical flow integration, are satisfied, a retailer can increase sustainable operations to increase efficiency. We have a surprising but reasonable finding: The interaction of sustainable operations and physical flow integration is negatively correlated to efficiency.<br/