Assessing the clinical utility of cancer genomic and proteomic data across tumor types

Molecular profiling of tumors promises to advance the clinical management of cancer, but the benefits of integrating molecular data with traditional clinical variables have not been systematically studied. Here we retrospectively predict patient survival using diverse molecular data (somatic copy-number alteration, DNA methylation and mRNA, miRNA and protein expression) from 953 samples of four cancer types from The Cancer Genome Atlas project. We found that incorporating molecular data with clinical variables yielded statistically significantly improved predictions (FDR < 0.05) for three cancers but those quantitative gains were limited (2.2–23.9%). Additional analyses revealed little predictive power across tumor types except for one case. In clinically relevant genes, we identified 10,281 somatic alterations across 12 cancer types in 2,928 of 3,277 patients (89.4%), many of which would not be revealed in single-tumor analyses. Our study provides a starting point and resources, including an open-access model evaluation platform, for building reliable prognostic and therapeutic strategies that incorporate molecular data

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

We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2

Interaction of electromagnetic waves in an ice layer

A mathematical model for spherical wave propagation near an ice layer has been developed. The proposed mathematical model is based on the directed Green’s functions with boundary conditions with irregular angles. Based on the suggested model, we analyzed a field of a point directed source radiating electromagnetic waves in two cases: the source is in the air and is radiating waves along the marine ice surface; the source is in the ice layer and radiating waves. Results of the modeling for different frequencies and different ice thickness are described. It was shown that wave amplitude increases by about two times inside the ice if compared to free space. Electromagnetic wave propagating along marine ice surface increases by 50% compared to the wave propagating in free space

Investigation of the channel for information transfer by electric, electromagnetic and acoustic waves in layered environment with ice cover

A theoretical model of electromagnetic wave propagation in an ice layer was developed. A half-wave vibrator frozen in an ice layer is used as a receiving-radiating system of electromagnetic waves. Schemes of developed acoustic low-frequency radiators based on electric sparks are described. The possibility of application of the developed systems to receive acoustic signals from earthquake ice source is under discussion

Investigation of electromagnetic fields in the arctic zone with uneven ice cover

Numerical investigation of electromagnetic waves propagating near an ice cover with hummocks of different height has been carried out. Half-wave vibrators, melted into ice at the depth of about 20 sm, were used as an antenna. Transmitted signal frequencies were from 10 to 30 MHz. A mathematical model for amplitude spatial distribution of electromagnetic wave source, placed inside an ice cover with hummocks, was developed. The results of numerical study show that, when antenna is inside hummocks, the signal is amplified. Experimental investigations show good agreement with the theoretical model

2D Hydro-Mechanical-Chemical Modeling of (De)hydration Reactions in Deforming Heterogeneous Rock: The Periclase-Brucite Model Reaction

Deformation at tectonic plate boundaries involves coupling between rock deformation, fluid flow, and metamorphic reactions, but quantifying this coupling is still elusive. We present a new two-dimensional hydro-mechanical-chemical numerical model and investigate the coupling between heterogeneous rock deformation and metamorphic (de)hydration reactions. We consider linear viscous compressible and power-law viscous shear deformation. Fluid flow follows Darcy's law with a Kozeny-Carman type permeability. We consider a closed isothermal system and the reversible (de)hydration reaction: periclase and water yields brucite. Fluid pressure within a circular or elliptical inclusion is initially below the periclase-brucite reaction pressure and above in the surrounding. Inclusions exhibit a shear viscosity thousand times smaller than for the surrounding. For circular inclusions, solid deformation has a minor impact on the evolution of fluid pressure, porosity, and reaction front. For elliptical inclusions and far-field shortening, rock pressure inside the inclusion is higher compared to circular inclusions, and reaction-front propagation is faster. The reaction generates a large change in porosity (∼0.1%–55%) and in solid density (∼2,300–3,500 kg m−3), and the reaction front exhibits steep gradients of fluid pressure and porosity. Reaction-front propagating increases the weak inclusion's surface and causes an effective, reaction-induced weakening of the heterogeneous rock. Weakening evolves nonlinear with progressive strain. Distributions of fluid and rock pressure as well as magnitudes and directions of fluid and solid velocities are significantly different. The models mimic basic features of shear zones and show the importance of coupling deformation and metamorphism. The applied MATLAB algorithm is provided

Meta-analysis of the clinical and immunopathological characteristics and treatment outcomes in epidermolysis bullosa acquisita patients

Background: Epidermolysis bullosa acquisita (EBA) is an orphan autoimmune disease. Several clinical phenotypes have been described, but subepidermal blistering is characteristic of all variants. Limited data on clinical and immunopathological characteristics and treatment outcomes in EBA are available. To fill this gap, we collected this information from EBA cases, meeting current diagnostic criteria, published between 1971 and 2016. Results: We identified 1159 EBA cases. This number must be, however, interpreted with caution, as it is not possible to check for multiple reporting. The analysis of all cases indicated that EBA affects all age groups (median: 50 years, range: 1 to 94 years) at an equal gender distribution. Non-mechanobullous (non-MB) forms of EBA were observed in 55% of patients, whereas the mechanobullous variant (MB-EBA) or a combination of both variants was described in 38 or 7% of patients, respectively. Type VII collagen (COL7)-specific autoantibodies were primarily of the IgG isotype, but anti-COL7 IgA, IgM and IgE were also documented. Comparison of the 2 clinical EBA types showed a higher frequency of IgA deposits in non-MB EBA as opposed to MB EBA. Mucous membrane involvement was observed in 23% of patients, and 4.4% of cases were associated with other chronic inflammatory diseases. Of note, IgA deposits were more frequently observed in cases with mucous membrane involvement. Our analysis indicated that EBA is difficult to treat and that the choice of treatment varies widely. Chi square was applied to identify medications associated with complete remission (CR). Considering all EBA cases, intravenous immunoglobulin (IVIG, p = 0.0047) and rituximab (p = 0.0114) were associated with CR. Subgroup analysis demonstrated that no treatment was associated with CR for non-MB EBA, while IVIG (p = 0.003) was associated with CR in MB EBA. Conclusions: Within the limitations of the study, we here document the clinical and immunopathological characteristics and treatment outcomes in a large cohort of EBA patients. The observed associations of single drugs with treatment outcome may serve as a guide to develop clinical trials