Remdesivir is a drug widely used for the etiotropic treatment of COVID-19. According to a number of studies, the incidence of adverse reactions during remdesivir therapy reaches 66%, with the most ...common is an increase in liver function tests.
The aim
of the work was to study the influence of clinical, demographic and pharmacogenetic factors on the development of drug-induced liver damage during remdesivir therapy in COVID-19 patients.
Materials and methods.
The study comprised 100 hospitalized patients treated with remdesivir. The patients were divided into two groups: group 1 (
n
=32) – remdesivir therapy, developed an increase in the level of liver transaminases; group 2 (control,
n
=68) – did not develop this adverse reaction. The patients in both groups underwent a pharmacogenetic study, and a retrospective analysis of medical records was performed. Based on the data obtained, the association of clinical, laboratory, pharmacological and pharmacogenetic parameters with the development of drug-induced liver damage during remdesivir therapy was studied.
Results.
In the group of patients with the development of drug-induced liver damage, people with a high body mass index were significantly more likely than in the control group (30.7±4.2 kg/m
2
in group 1
vs.
27.3±5.5 kg/m
2
in group 2,
p
=0.003), with a history of diabetes mellitus (odds ratio (OR)=2.647, 95% confidence interval (CI)=1.092–6.414, χ
2
=4.785,
p
=0.029), with higher levels of ferritin in the blood (724.03±432.27 and 553.19±358.48 mg/mol, respectively,
p
=0.040), receiving therapy with angiotensin-converting enzyme inhibitors (OR=5.440, 95% CI=2.160–13.699, χ
2
=14.027,
p
=0.000), statins (OR=3.148, 95% CI=1.307–7.581, χ
2
=6.795,
p
=0.009), and also being heterozygous for the polymorphic marker
rs776746
of the
CYP3A5
gene (OR=3.961, 95% CI=1.343–11.686, χ
2
=6.772,
p
=0.009).
Conclusion.
A high body mass index, a history of diabetes mellitus, high levels of ferritin in the blood, concomitant therapy with angiotensin-converting enzyme inhibitors and statins, as well as a carriage of the AG genotype for the polymorphic marker
rs776746
of the
CYP3A5
gene increase the likelihood of developing drug-induced liver damage during remdesivir therapy. In this regard, it is necessary to consider these factors when prescribing remdesivir therapy, conduct a more careful monitoring of clinical and laboratory indicators of liver damage, and develop personalized approaches to the treatment of COVID-19 patients.
The contribution of irradiation-induced enrichment of grain boundaries by impurities to irradiation embrittlement of reactor pressure vessel materials is discussed. Possible mechanisms of impurities ...and the effect of alloying elements on irradiation embrittlement of reactor pressure vessel steels are considered. Nickel has been found to influence greatly the tendency to irradiation embrittlement of nickel-containing steels with Ni wt% > 0.9. Irradiation resistance of nickel-containing steels has been shown to decrease significantly with the increase of silicon concentration from 0.24–0.28 to 0.3–0.4 wt%. The model for irradiation-induced enrichment of grain boundaries by impurities is used in order to explain the effect of silicon and nickel on irradiation embrittlement. In terms of the model, Si and Ni themselves do not prove the embrittlement, but they only influence thermodynamic and kinetic parameters of the phosphorus gain boundary adsorption. The embrittlement process itself is a result of decreasing of grain boundary cohesion with formation of phosphorus irradiation-induced grain boundary segregation.
A brief analysis of different approaches to the calculation and measurement of the condensation coefficient of a vapor is presented. It is shown that, on frequent occasions, calculations give values ...of this coefficient that are at variance with the corresponding experimental data and that the condensation coefficient is determined most exactly on the basis of the molecular-kinetic theory. It was established that the spread in the literature data on the measured values of this coefficient is explained mainly by the fact that these values were obtained not in the immediate vicinity from the boundary between the gas and liquid phases but at a large distance (as compared to the mean free path of molecules) from it. Results of calculations of the condensation coefficient of argon by the method of moleculardynamic simulation are presented.
The paper presents a REDUCE program for the simplification of tensor expressions that are considered as formal indexed objects. The proposed algorithm is based on the consideration of tensor ...expressions as vectors in some linear space. This linear space is formed by all the elements of the group algebra of the corresponding tensor expression. Such approach permits us to simplify the tensor expressions possessing symmetry properties, summation (dummy) indices and multiterm identities by unify manner. The canonical element for the tensor expression is defined in terms of the basic vectors of this linear space. The main restriction of the algorithm is the dimension of the linear space that is equal to
N!, where
N is a number of indices of the tensor expression. The program uses REDUCE as user interface.
The evaluation and prognosis of reactor pressure vessel (RPV) material embrittlement in WWERs and the allowable period of their safe operation are performed on the basis of impact test results of ...irradiated surveillance specimens. The main problem concerns the irradiation conditions (irradiation temperature, neutron flux and neutron spectrum) of the surveillance specimens that have not been determined yet with the necessary accuracy. These conditions could differ from the actual RPV wall condition. In particular, the key issue is the possible difference between the irradiation temperature of the surveillance specimens and the actual RPV wall temperature. It is recognized that the direct measurement of the irradiation temperature by thermocouples during reactor operation is the only way to obtain reliable information. In addition, the neutron field's parameters in the surveillance specimens location have not been determined yet with the necessary accuracy. The use of state of the art dosimeters can provide high accuracy in the determination of the neutron exposure level.
The COBRA project, which started in August 2000 and had a duration of 3 years, was designed to solve the above-mentioned problems. Surveillance capsules were manufactured which contained state of art dosimeters and temperature monitors (melting alloys). In addition, thermocouples were installed throughout the instrumentation channels of the vessel head to measure directly the irradiation temperature in the surveillance position during reactor operation. The selected reactor for the experiment was the Unit 3 of Kola NPP situated in the arctic area of Russia. Irradiation of capsules and online temperature measurements were performed during one fuel cycle. On the base of statistical processing of thermocouples readings, the temperature of irradiated surveillance specimens in WWER-440/213 reactor can be accepted as 269.5
±
4
°C. Uncertainties were evaluated also with experimental work carried out in the WWRSZ research reactor and by finite element modelling of surveillance capsules. The results obtained show that there is not need to perform temperature correction when surveillance data of irradiated specimens are used for embrittlement assessment of WWER-440(213) reactor pressure vessels. Maximum neutron flux evaluated using detectors, which were placed in the Charpy specimen simulators, equals ∼2.7
×
10
12
cm
−2
s
−1 with
E
>
0.5
MeV. It is established that depending on the orientation of the capsules with respect to the core, the detectors of the standard surveillance capsules can give both overestimated and underestimated neutron flux values, as compared to the actual flux received by the surveillance specimens. The overestimation or underestimation can reach 10%.
The numerical calculations of flows in conical and contoured nozzles with slots in the supersonic part that operate under overexpansion conditions are presented. The calculations were made with the ...aid of the authors’ algorithm and program of simulating turbulent two-dimensional (axisymmetric) flows of a viscous heat-conducting gas. The results of computational investigations of tractive slot nozzle characteristics and the amount of combustion product leakage from an annular slot depending on the flight altitude are given. It is shown that the flight altitude at which the gas flow through the annular slot is “chocked” depends on its size and location in the supersonic nozzle part.
Certain modifications of three-equation turbulence models are proposed. They are intended for increasing the accuracy of the calculations of turbulent flows in nozzles with boundary layer separation ...and in supersonic jets with complicated shock wave structures. Basing on the idea of the inclusion of flow prehistory in terms of an additional relaxation equation for nonequilibrium turbulent viscosity we propose three modifications of the
k
-
ω
-µ
t
model based on the
k
-
ω
model and a version of the
k
-
ɛ
-µ
t
turbulence model. In these modifications we introduce an additional dependence of the nonequilibrium turbulent viscosity relaxation time on different physical parameters which can be important near the point of boundary layer separation from the nozzle wall, such as viscous effects and effects of large gradients of the mean velocity and the kinetic energy of turbulence (turbulent pressure). The comparison of the results of the calculations with the experimental data shows that all the proposed versions of the three-equation models make it possible to improve the accuracy of the calculations of turbulent flows in nozzles and jets.
The temperature and field dependences of the magnetic moment of Nb(
x)/Ni(
y)
5 multilayers are reported. Small kinks in the phase boundary defined in field-cooled AC experiments exhibit an ...approximate period of 733
Oe, and persist to a DC field
H=6.5
kOe applied parallel to the multilayer. A second group of cusp anomalies in DC magnetization are observed for
H<100
Oe with approximate period 15–20
Oe. The absence of anomalies in perpendicular field and normal state data suggest they are due to finite-size effects expected when the superconducting layer is thinner than the magnetic penetration depth.
The results of magnetic resonance imaging (MRI) of the inner ear 24 hours after intratympanic administration of 1 ml of diluted (1:7) contrast substance for gadolinium-based MRI in 43 patients with ...moderate and severe Meniere's disease course are presented. It has been revealed that in case of severe and moderate course of Meniere's disease endolymphatic hydrops is presented in all departments of labyrinth: cochlea, vestibule, semicircular canals, but is most pronounced in vestibular department of labyrinth: horizontal semicircular canal and vestibule. The neuroimaging method according to the presented protocol is safe and can be applied in a wide practice both to assess the presence and localization, and the degree of expression of the endolymphatic hydrops.
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