Effect of Canakinumab vs Placebo on Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19: A Randomized Clinical Trial.

Importance: Effective treatments for patients with severe COVID-19 are needed. Objective: To evaluate the efficacy of canakinumab, an anti-interleukin-1ß antibody, in patients hospitalized with severe COVID-19. Design, Setting, and Participants: This randomized, double-blind, placebo-controlled phase 3 trial was conducted at 39 hospitals in Europe and the United States. A total of 454 hospitalized patients with COVID-19 pneumonia, hypoxia (not requiring invasive mechanical ventilation [IMV]), and systemic hyperinflammation defined by increased blood concentrations of C-reactive protein or ferritin were enrolled between April 30 and August 17, 2020, with the last assessment of the primary end point on September 22, 2020. Intervention: Patients were randomly assigned 1:1 to receive a single intravenous infusion of canakinumab (450 mg for body weight of 40-<60 kg, 600 mg for 60-80 kg, and 750 mg for >80 kg; n = 227) or placebo (n = 227). Main Outcomes and Measures: The primary outcome was survival without IMV from day 3 to day 29. Secondary outcomes were COVID-19-related mortality, measurements of biomarkers of systemic hyperinflammation, and safety evaluations. Results: Among 454 patients who were randomized (median age, 59 years; 187 women [41.2%]), 417 (91.9%) completed day 29 of the trial. Between days 3 and 29, 198 of 223 patients (88.8%) survived without requiring IMV in the canakinumab group and 191 of 223 (85.7%) in the placebo group, with a rate difference of 3.1% (95% CI, -3.1% to 9.3%) and an odds ratio of 1.39 (95% CI, 0.76 to 2.54; P = .29). COVID-19-related mortality occurred in 11 of 223 patients (4.9%) in the canakinumab group vs 16 of 222 (7.2%) in the placebo group, with a rate difference of -2.3% (95% CI, -6.7% to 2.2%) and an odds ratio of 0.67 (95% CI, 0.30 to 1.50). Serious adverse events were observed in 36 of 225 patients (16%) treated with canakinumab vs 46 of 223 (20.6%) who received placebo. Conclusions and Relevance: Among patients hospitalized with severe COVID-19, treatment with canakinumab, compared with placebo, did not significantly increase the likelihood of survival without IMV at day 29. Trial Registration: ClinicalTrials.gov Identifier: NCT04362813.

Compound-tunable embedding potential: which oxidation state of uranium and thorium as point defects in xenotime is favorable?

Modern strategies for the safe handling of high level waste (HLW) and its long-term disposal in deep geological formations include the immobilization of radionuclides in the form of mineral-like matrices. The most promising matrices for the immobilization of actinides are ceramic forms of waste based on phosphate minerals such as monazite, xenotime, and cheralite. However, the mechanism of substitution of lanthanides and Y by actinides in phosphate minerals is not entirely clear. We formulated a theoretical model, compound-tunable embedding potential (CTEP), that allows one to predict properties of such crystals with point defects. The reliability of the model is validated by a good agreement of calculated geometry parameters with available experimental data. The substitution of Y in the xenotime crystal by Th and U is studied by relativistic DFT in the framework of the CTEP method, based on constructing the embedding potential as the linear combination of short-range "electron-free" spherical "tunable" pseudopotentials. It is shown on the basis of the proposed model that oxidation state +3 is energetically more profitable than +4 not only for thorium but also for uranium as solitary point defects. This atypical oxidation state of U in the mineral is discussed.

On the issue of comparing the immobilization characteristics of matrix materials based on Nb-Ta-Ti-oxides of the types AB2O6 and A2B2O7.

In the study presented here, the initial (that is, before the start of the process of natural hydrochemical influence) mineral formula of metamict polycrase in the composition of granite pegmatites of the Baltic Shield, applying an uranium natural half-leaching period, was calculated. To investigate the characteristics of immobilization of actinides in the studied polycrase, the absolute and relative uranium contents are compared with the corresponding uranium contents in the original betafite of the same deposit and age. It has been shown that over its geological history, betafite has lost up to 80% of its original uranium content. The proportion of uranium preserved in polycrase is twice as high. It is concluded that the difference in the relative content of uranium (27.3 wt% in polycrase and 31.6 wt% in betafite) cannot be the only reason for the complete oxidation of uranium in betafite, given that in polycrase 30% of uranium is preserved in the tetravalent state. It is more likely that the oxidation of uranium in betafite was primarily a result of the low ionicity of the chemical bonds compared to that in polycrase. This allows us to consider minerals of the euxenite group to be quite promising as matrix materials for the immobilization of actinides. At the same time, an opinion was expressed on the advisability of further comparative studies of Nb-Ta-Ti-oxides of the mineral groups AB2O6 and A2B2O7 for their use at the final stage of the nuclear fuel cycle.

Association between Current Substance Use, Healthy Behaviors, and Depression among Ukrainian College Students.

Depression is a pervasive issue among college students worldwide, yet there is a significant gap in the literature regarding its prevalence and coping strategies in the Ukrainian context. The present study aims to fill this gap by investigating how substance use and health-promoting behaviors relate to depressive symptoms among Ukrainian college students. Health-promoting behaviors are an important strategy to prevent depression, whereas substance use can contribute to depression or make it harder to manage. Given the substantial psychosocial problems and stressors related to the ongoing war in Ukraine and the limited availability of mental health services for college students, it is important to understand how we can encourage college students to keep themselves mentally healthy. A cross-sectional study was conducted among college students on 10 campuses in 2018. Almost 16% of participants met a cut-off for depression. Female students and those who were older reported significantly higher depressive symptoms. Participants were more likely to report depressive symptoms if they were more often involved with alcohol and cannabis use, were older, and engaged in fewer health-promoting behaviors. Tobacco use was not significantly associated with depressive symptoms. Our findings suggest a moderate prevalence of depressive symptoms in our study population. We recommend implementing balanced public health interventions that address risk factors (such as substance use) while also promoting protective behaviors and can be tailored to the specific cultural and environmental context of the region.

On the feasibility of determining the 230Th activity in minerals without the addition of a Th radiotracer.

The necessity of measuring the radioactivity of the 230Тh nuclide arises when attempting to solve a number of geochemical or geochronological problems based on the effects of radioactive disequilibrium in the 238U series. It is the authors' opinion that the use of the traditional α- and ß-emitters of thorium as a radiotracer in order to determine the activity of 230Тh leads to various inconveniences and difficulties of a technical nature. The authors recommend using the 234Тh isotope contained in the study sample as the simplest and most natural way of measuring the chemical yield of the targeted nuclide (230Тh). A sequence of radio-analytical procedures is proposed that will provide a correct assessment of the radioactivity of 230Тh. In addition, a specific example and an evaluation of the accuracy of the proposed methodology are presented, using actual experimental data.

Non- identical thermochemical behavior of 234U-and 238U- isotopes in metamict britholite.

A radiochemical analysis of the valence state of uranium isotopes in minerals involves isolation of the U(IV) and U(VI) valence forms and determination of the radioactivity of the 234U and 238U isotopes in each fraction. If the nuclear decay of the uranium in the minerals is accompanied by a redox process, the distribution of the 234U isotope in the U(IV) and U(VI) forms will differ from that of the 238U isotope: oxidation leads to enrichment of the U(VI) fraction with the radiogenic 234U isotope; reduction facilitates enrichment of the U(IV) fraction with 234U. If the mineral is heated to 600-700°C before the radiochemical analysis, then an equilibrium activity ratio (AR) for both valences. The question arises: What are the processes that bring this about? The authors of this research studied changes of the AR in the U(IV) and U(VI) fractions after isochronous thermal annealing.