Polymyxin B hemoperfusion therapy and extracorporeal CO2 removal in a patient with COVID-19: A case report

Introduction: In December 2019, an outbreak of pneumonia caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) quickly spread and the corona virus disease 2019 (COVID-19) became a pandemic. We report on a 54-year-old patient with SARS-CoV-2 infection suffering from septic shock due to nosocomial infection and pulmonary derangement caused by SARS-CoV-2. The patient was treated with polymyxin B hemoperfusion (PMX-HP), a blood purification therapy against septic shock, followed by continuous low flow extracorporeal CO2 removal therapy. Case Report: A 54-year-old man was hospitalized for coronavirus disease 2019 (COVID-19). Chest computed tomography (CCT) showed extensive non-segmental ground glass opacity. Despite the initiation of standard therapy, respiratory failure progressed. After two days of polymyxin B hemoperfusion therapy (PMX-HP) with adjunctive corticosteroid for multi-resistant Gram-negative infection (Acinetobacter) the patient's condition improved. In rapidly progressive COVID-19 cases with secondary infection, the early use of PMX-HP may avoid the need for mechanical ventilation by suppressing local inflammation of the lung. Conclusion: The concern of life-threatening bacterial infections in critically ill COVID-19 patients due to antibiotics resistance is high. Secondary bacterial infections may develop during or following COVID-19 infection. The use of PMX-HP in septic shock patients has resulted in decreased dependency on ventilators, which is a serious issue during this COVID-19 pandemic. Combined and less invasive approaches might be considered in COVID-19 patients with multiple organ failure (MOF)

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

Peak-Shaped-Based Steganographic Technique for MP3 Audio

The aim of this work is the development of a steganographic technique for the MP3 audio format, which is based on the Peak Shaped Model algorithm used for JPEG images. The proposed method relies on the statistical properties of MP3 samples, which are compressed by a Modified Discrete Cosine Transform (MDCT). After the conversion of MP3, it’s possible to hide some secret information by replacing the least significant bit of the MDCT coefficients. Those coefficients are chosen according to the statistical relevance of each coefficient within the distribution. The performance analysis has been made by calculating three steganographic parameters: the Embedding Capacity, the Embedding Efficiency and the PSNR. It has been also simulated an attack with the Chi-Square test and the results have been used to plot the ROC curve, in order to calculate the error probability. Performances have been compared with performances of other existing techniques, showing interesting results

Author Correction: Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing (Nature Genetics, (2019), 51, 3, (414-430), 10.1038/s41588-019-0358-2)

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Author Correction: Genetic meta-analysis of diagnosed Alzheimer\u27s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease.

We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10-10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10-14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease

CEPC Conceptual Design Report: Volume 2 - Physics & Detector

The Circular Electron Positron Collider (CEPC) is a large international scientific facility proposed by the Chinese particle physics community to explore the Higgs boson and provide critical tests of the underlying fundamental physics principles of the Standard Model that might reveal new physics. The CEPC, to be hosted in China in a circular underground tunnel of approximately 100 km in circumference, is designed to operate as a Higgs factory producing electron-positron collisions with a center-of-mass energy of 240 GeV. The collider will also operate at around 91.2 GeV, as a Z factory, and at the WW production threshold (around 160 GeV). The CEPC will produce close to one trillion Z bosons, 100 million W bosons and over one million Higgs bosons. The vast amount of bottom quarks, charm quarks and tau-leptons produced in the decays of the Z bosons also makes the CEPC an effective B-factory and tau-charm factory. The CEPC will have two interaction points where two large detectors will be located. This document is the second volume of the CEPC Conceptual Design Report (CDR). It presents the physics case for the CEPC, describes conceptual designs of possible detectors and their technological options, highlights the expected detector and physics performance, and discusses future plans for detector R&D and physics investigations. The final CEPC detectors will be proposed and built by international collaborations but they are likely to be composed of the detector technologies included in the conceptual designs described in this document. A separate volume, Volume I, recently released, describes the design of the CEPC accelerator complex, its associated civil engineering, and strategic alternative scenarios