Metabolic and Lipidomic Markers Differentiate COVID-19 From Non-Hospitalized and Other Intensive Care Patients

Coronavirus disease 2019 (COVID-19) is a viral infection affecting multiple organ systems of great significance for metabolic processes. Thus, there is increasing interest in metabolic and lipoprotein signatures of the disease, and early analyses have demonstrated a metabolic pattern typical for atherosclerotic and hepatic damage in COVID-19 patients. However, it remains unclear whether this is specific for COVID-19 and whether the observed signature is caused by the disease or rather represents an underlying risk factor. To answer this question, we have analyzed 482 serum samples using nuclear magnetic resonance metabolomics, including longitudinally collected samples from 12 COVID-19 and 20 cardiogenic shock intensive care patients, samples from 18 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody-positive individuals, and single time point samples from 58 healthy controls. COVID-19 patients showed a distinct metabolic serum profile, including changes typical for severe dyslipidemia and a deeply altered metabolic status compared with healthy controls. Specifically, very-low-density lipoprotein and intermediate-density lipoprotein particles and associated apolipoprotein B and intermediate-density lipoprotein cholesterol were significantly increased, whereas cholesterol and apolipoprotein A2 were decreased. Moreover, a similarly perturbed profile was apparent when compared with other patients with cardiogenic shock who are in the intensive care unit when looking at a 1-week time course, highlighting close links between COVID-19 and lipid metabolism. The metabolic profile of COVID-19 patients distinguishes those from healthy controls and also from patients with cardiogenic shock. In contrast, anti-SARS-CoV-2 antibody-positive individuals without acute COVID-19 did not show a significantly perturbed metabolic profile compared with age- and sex-matched healthy controls, but SARS-CoV-2 antibody-titers correlated significantly with metabolic parameters, including levels of glycine, ApoA2, and small-sized low- and high-density lipoprotein subfractions. Our data suggest that COVID-19 is associated with dyslipidemia, which is not observed in anti-SARS-CoV-2 antibody-positive individuals who have not developed severe courses of the disease. This suggests that lipoprotein profiles may represent a confounding risk factor for COVID-19 with potential for patient stratification.

Another Superdense Sub-Neptune in K2-182 b and Refined Mass Measurements for K2-199 b and c*

We combine multiple campaigns of K2 photometry with precision radial velocity measurements from Keck-HIRES to measure the masses of three sub-Neptune-sized planets. We confirm the planetary nature of the massive sub-Neptune K2-182 b (P b = 4.7 days, R b = 2.69 R ⊕) and derive refined parameters for K2-199 b and c (P b = 3.2 days, R b = 1.73 R ⊕ and P c = 7.4 days, R c = 2.85 R ⊕). These planets provide valuable data points in the mass–radius plane, especially as TESS continues to reveal an increasingly diverse sample of sub-Neptunes. The moderately bright (V = 12.0 mag) early K dwarf K2-182 (EPIC 211359660) was observed during K2 campaigns 5 and 18. We find that K2-182 b is potentially one of the densest sub-Neptunes known to date (20 ± 5 M ⊕ and 5.6 ± 1.4 g cm−3). The K5V dwarf K2-199 (EPIC 212779596; V = 12.3 mag), observed in K2 campaigns 6 and 17, hosts two recently confirmed planets. We refine the orbital and planetary parameters for K2-199 b and c by modeling both campaigns of K2 photometry and adding 12 Keck-HIRES measurements to the existing radial velocity data set (N = 33). We find that K2-199 b is likely rocky, at 6.9 ± 1.8 M ⊕ and 7.2 − 2.0 + 2.1 g cm−3, and that K2-199 c has an intermediate density at 12.4 ± 2.3 M ⊕ and 2.9 − 0.6 + 0.7 g cm−3. We contextualize these planets on the mass–radius plane, discuss a small but intriguing population of “superdense” sub-Neptunes (R p < 3 R ⊕, M p >20 M ⊕), and consider our prospects for the planets’ atmospheric characterization.

Clinical Significance of Intermediate-Density Lipoprotein Cholesterol Determination as a Predictor for Coronary Heart Disease Risk in Middle-Aged Men

Background: Not only low-density lipoprotein (LDL) cholesterol but also non-high-density lipoprotein cholesterol (non-HDL-C), very low-density lipoprotein (VLDL) cholesterol (VLDL-C), and intermediate-density lipoprotein (IDL) cholesterol (IDL-C) are reported to be significant risk markers for coronary heart disease (CHD). We reported the relevance of IDL-C to Framingham risk score (F-score), but the present study addressed the relevance of IDL-C to Suita score (S-score), a risk score for coronary heart disease (CHD) developed for the Japanese individuals in addition to F-score.Methods: The cholesterol levels of lipoproteins, including triglyceride (TG)-rich lipoproteins (IDL and VLDL), were measured by an anion exchange high-performance liquid chromatography (AEX-HPLC). This study enrolled 476 men, aged mean 51 years and free of CHD and stroke.Results: Non-HDL-C, IDL-C, and VLDL-C significantly correlated with F-score and S-score. In the multiple stepwise regression analysis, IDL-C as well as body mass index (BMI) significantly correlated with both F-score and S-score in both the total subjects and the subjects without drug therapy. The multivariate logistic analysis with the model composed of BMI and IDL-C as the predictor variables demonstrated that 1 SD increase in IDL-C was an independent predictor for 10-year CHD risk &gt;10% of F-score (OR 1.534, 95% CI 1.266–1.859, p &lt; 0001) and that of S-score (OR 1.372, 95% CI 1.130–1.667, p = 0.0014) in the total subjects. Even in the subjects without the drug therapy, the increased IDL-C, as well as BMI, were significant predictors for 10-year CHD risk &gt;10% of S-score as well as F-score.Conclusion: These results suggest the significant relevance of the increased IDL-C for CHD risk scores in middle-aged men free of CHD and stroke. Further investigations are needed in women and elderly subjects.

THE ANALYSIS OF ADMISSIBLE LEVEL OF FORMALDEHYDE IN AIR

By production of glued and plate wood-base materials with use of carboamidoformaldehyde pitches (KFS) the main lack of technology of which is toxicity of these materials to the person. Toxicity is caused by allocation from these materials of gas, harmful to the person, - formaldehyde which is cancerogenic substance. Wood-shaving plates from needle (DSTP) and large-size shaving (OSB), fiber boards (DVP) including the Intermediate-density fiberboard (MDF), and also plywood of general purpose and different types of special plywood (decorative, bakelized, etc.), first of all, belong to such materials. The Russian Ministry of Health has established very strict requirements on release of formaldehyde in air both in premises, and in free air the admissible level of which makes (DU) only 0,01 mg/m3 of air when testing materials by chamber method. The plate materials released now can exceed DU of 17 times stated above. Especially it concerns DSTP. Despite attempts of institute Vniidrev through appeals to relevant authorities of the Ministry of Health to increase such admissible level in our country, generally for plate materials, were not crowned with success yet and this level in real time remains in force. It is possible to use such plates in premises only at very small saturation them room void volume (the saturation is defined as the relation of surface area of plates indoors to room void volume). So, by our researches for example it is proved that the written dvukhtumbovy table made of DSTP of class of release of formaldehyde E2 can be established in living room of 20 sq.m only one and no more. Only in this case, at small saturation room void volume plates, the release of formaldehyde in air of the room will meet requirements of domestic DU. In premises the case furniture is in reality with much bigger saturation that leads to room gas contamination formaldehyde. In too time abroad formaldehyde size DU in air much more also makes 0,124 mg/m3 of air. In this regard the purpose of our work consisted in the analysis of DU of formaldehyde in air of foreign researches.

COVID-19 in pregnancy: placental pathological patterns and effect on perinatal outcome in five cases

Introduction COVID-19, the disease caused by the novel coronavirus SARS-CoV-2, is a severe systemic thrombotic syndrome that emerged in 2019, with an ensuing pandemic. To evaluate the impact of this disease on placental tissue and perinatal outcome, histological, immunohistochemical and ultrastructural analyses of placental tissue were performed for five cases of pregnant women with COVID-19. Case reports All five pregnant women in this series developed COVID-19 in late pregnancy. Two patients experienced respiratory distress, and computed tomography revealed signs of pneumonia, with bilateral involvement, multiple lobular and subsegmental areas of consolidation and ground-glass opacities. Histological studies of placental tissue revealed the presence of slight signs of maternal vascular underperfusion (MVUs) or foetal vascular underperfusion (FVUs) lesions and mild inflammatory lesions. CD15 immunoreactivity in the placental tissue was low in all cases, demonstrating that in these cases there was not severe foetal hypoxia/asphyxia risk for newborns or distal vascular immaturity. In all cases examined, ultrastructural analyses showed spherical-like coronavirus particles with an electron intermediate-density core as well as projections from the surface as spike-like structures in the syncytiotrophoblasts. At term, all of the women delivered newborns who were negative for SARS-CoV-2 by nasopharyngeal testing in their first day of life. All newborns were exclusively breastfed and were discharged on the 3rd day of life. Conclusions In conclusion, placental patterns in pregnancy due to COVID-19 in the late stage of gestation indicate no evidence of vertical trans-placental SARS-CoV-2 transmission or a significant impact on the perinatal outcome of newborns, in both mild and more severe cases.

Reachability Deficits in Quantum Approximate Optimization of Graph Problems

The quantum approximate optimization algorithm (QAOA) has become a cornerstone of contemporary quantum applications development. Here we show that the density of problem constraints versus problem variables acts as a performance indicator. Density is found to correlate strongly with approximation inefficiency for fixed depth QAOA applied to random graph minimization problem instances. Further, the required depth for accurate QAOA solution to graph problem instances scales critically with density. Motivated by Google's recent experimental realization of QAOA, we preform a reanalysis of the reported data reproduced in an ideal noiseless setting. We found that the reported capabilities of instances addressed experimentally by Google, approach a rapid fall-off region in approximation quality experienced beyond intermediate-density. Our findings offer new insight into performance analysis of contemporary quantum optimization algorithms and contradict recent speculation regarding low-depth QAOA performance benefits.

Revisiting non-convexity in topology optimization of compliance minimization problems

PurposeThis is an attempt to better bridge the gap between the mathematical and the engineering/physical aspects of the topic. The authors trace the different sources of non-convexification in the context of topology optimization problems starting from domain discretization, passing through penalization for discreteness and effects of filtering methods, and end with a note on continuation methods.Design/methodology/approachStarting from the global optimum of the compliance minimization problem, the authors employ analytical tools to investigate how intermediate density penalization affects the convexity of the problem, the potential penalization-like effects of various filtering techniques, how continuation methods can be used to approach the global optimum and how the initial guess has some weight in determining the final optimum.FindingsThe non-convexification effects of the penalization of intermediate density elements simply overshadows any other type of non-convexification introduced into the problem, mainly due to its severity and locality. Continuation methods are strongly recommended to overcome the problem of local minima, albeit its step and convergence criteria are left to the user depending on the type of application.Originality/valueIn this article, the authors present a comprehensive treatment of the sources of non-convexity in density-based topology optimization problems, with a focus on linear elastic compliance minimization. The authors put special emphasis on the potential penalization-like effects of various filtering techniques through a detailed mathematical treatment.

Accurate Electron Drift Mobility Measurements in Moderately Dense Helium Gas at Several Temperatures

We report new accurate measurements of the drift mobility μ of quasifree electrons in moderately dense helium gas in the temperature range 26K≤T≤300K for densities lower than those at which states of electrons localized in bubbles appear. By heuristically including multiple-scattering effects into classical kinetic formulas, as previously done for neon and argon, an excellent description of the field E, density N, and temperature T dependence of μ is obtained. Moreover, the experimental evidence suggests that the strong decrease of the zero-field density-normalized mobility μ0N with increasing N from the low up to intermediate density regime is mainly due to weak localization of electrons caused by the intrinsic disorder of the system, whereas the further decrease of μ0N for even larger N is due to electron self-trapping in cavities. We suggest that a distinction between weakly localized and electron bubble states can be done by inspecting the behavior of μ0N as a function of N at intermediate densities.

Evolution of urban forms observed from space

Multiple driving forces shape cities. These forces include the costs of transporting goods and people, the types of predominant local industries, and the policies that govern urban planning. Here, we examine how agglomeration and dispersion change with increasing population and population density. We study the patterns in the evolution of urban forms and analyze the differences between developed and developing countries. We analyze agglomeration across 233 European and 258 Chinese cities using nighttime luminosity data. We find a universal inverted U-shape curve for the agglomeration metric (Lasym index). Cities attain their maximum agglomeration level at an intermediate density, above which dispersion increases. Our findings may guide strategic urban planning for the timely adoption of appropriate development policies.

Are Vapor-Like Fluids Viable Ore Fluids for Cu-Au-Mo Porphyry Ore Formation?

Ore formation in porphyry Cu-Au-(Mo) systems involves the exsolution of metal-bearing fluids from magmas and the transport of the metals in magmatic-hydrothermal plumes that are subject to pressure fluctuations. Deposition of ore minerals occurs as a result of cooling and decompression of the hydrothermal fluids in partly overlapping ore shells. In this study, we address the role of vapor-like fluids in porphyry ore formation through numerical simulations of metal transport using the Gibbs energy minimization software, GEM-Selektor. The thermodynamic properties of the hydrated gaseous metallic species necessary for modeling metal solubility in fluids of moderate density (100–300 kg/m3) were derived from the results of experiments that investigated the solubility of metals in aqueous HCl- and H2S-bearing vapors. Metal transport and precipitation were simulated numerically as a function of temperature, pressure, and fluid composition (S, Cl, and redox). The simulated metal concentrations and ratios are compared to those observed in vapor-like and intermediate-density fluid inclusions from porphyry ore deposits, as well as gas condensates from active volcanoes. The thermodynamically predicted solubility of Cu, Au, Ag, and Mo decreases during isothermal decompression. At elevated pressure, the simulated metal solubility is similar to the metal content measured in vapor-like and intermediate-density fluid inclusions from porphyry deposits (at ~200–1,800 bar). At ambient pressure, the metal solubility approaches the metal content measured in gas condensates from active volcanoes (at ~1 bar), which is several orders of magnitude lower than that in the high-pressure environment. During isochoric cooling, the simulated solubility of Cu, Ag, and Mo decreases, whereas that of Au reaches a maximum between 35 ppb and 2.6 ppm depending on fluid density and composition. Similar observations are made from a compilation of vapor-like and intermediate-density fluid inclusion data showing that Cu, Ag, and Mo contents decrease with decreasing P and T. Increasing the Cl concentration of the simulated fluid promotes the solubility of Cu, Ag, and Au chloride species. Molybdenum solubility is highest under oxidizing conditions and low S content, and gold solubility is elevated at intermediate redox conditions and elevated S content. The S content of the vapor-like fluid strongly affects metal ratios. Thus, there is a decrease in the Cu/Au ratio as the S content increases from 0.1 to 1 wt %, whereas the opposite is the case for the Mo/Ag ratio; at S contents of &gt;1 wt %, the Mo/Ag ratio also decreases. In summary, thermodynamic calculations based on experiments involving gaseous metallic species predict that vapor-like fluids may transport and efficiently precipitate metals in concentrations sufficient to form porphyry ore deposits. Finally, the fluid composition and pressure-temperature evolution paths of vapor-like and intermediate-density fluids have a strong effect on metal solubility in porphyry systems and potentially exert an important control on their metal ratios and zoning.