Vol 46, No 11 (2019)

In 2017, a group of the leading mathematical statisticians published a paper-manifesto having an extremely simple sense: the common critical level of p-values should be decreased by an order of magnitude (0.005 instead of 0.05) (Benjamin, et al., 2017). In this review, the arguments of proponents and opponents of this proposal are discussed. Moreover, the problems related to the “reproducibility crisis” of the scientific results are considered. The corresponding argumentation cannot be understood without consideration of the fundamentals of the theory of statistical derivation. In this connection, the precise sense of some concepts, such as p-value, the Bayes factor, and the minimum a posteriori probability of the zero hypothesis are discussed in the review. This is made mainly with the examples related to the comparison of frequencies. It was shown that, when using p-values, particular attention should be paid to the comparison of low frequencies on the highly abundant samples. Some practical recommendations on application of the Bayes analysis are given.

The results of applying the method of prognosis of post-radiation curves of neutrophil count dynamics in the blood after acute nonuniform human irradiation based on the use of a special computer program and the results of cytogenetic analysis of the cultures of peripheral blood lymphocytes are presented. The computer program converts the distribution of the cells by the number of dicentrics in them into the distribution of lymphocytes by dose received. Data obtained from 10 patents injured in six different radiation incidents were processed. To take into account radiation-induced proliferation delay and interphase cell death, correction of the observed distributions of dicentric chromosomes was carried out. The comparison of real and predicted curves of neutrophil count dynamics indicates in general their satisfactory compliance.

The radiation risk for astronauts in long space flights depends on the impact of low-intensity galactic and solar radiation on the spaceship. There is a small possibility of high solar activity during long space flights, which can threaten astronauts with doses causing deterministic radiation effects. B-190 (indralin) is the most promising radioprotector of the small number of radioprotective drugs allowed for use in humans. The antiemetic Latran (ondansetron) is of interest for prophylaxis of, and stopping the primary radiation response. Application of radiomitigators during proton radiation makes it possible to accelerate post-radiation recovery processes in hematopoietic tissue. Neupomax has been suggested for pathogenetic therapy of acute radiation illness. Natural antioxidants, drugs, nutritional supplements as radiomodulators, high-quality nutrition including vegetable products enriched with flavonoids and vitamins C and E, and carotin potentially promote prevention of accelerated aging in astronauts during long flights under the influence of solar and galactic cosmic rays and space flight stress factors.

An analysis of the current status and future directions of developing medicines for the prevention and early treatment of radiation damage has been conducted. Among radioprotectors, only B-190 (Indralin) is approved for use in the Russian Federation; the main radioprotector in foreign countries is amifostine (Ethyol). Some prospects in the development of new radioprotectors are associated with inhibitors of NO-synthases from the class of N-acyl-S-alkyl-substituted isothiourea derivatives, among which chemical compounds with a pronounced radioprotective effect are found. A recombinant human interleukin-1β (Betaleukin) has been registered in Russia as a radiomitigator intended for use in the early period after accidental irradiation. The US Food and Drug Administration (FDA) has approved the investigational new drug status for seven radiomitigators, including 5-androstenediol (Neumune), genistein (BIO 300), CBLB502 (Entolimod), a kinase inhibitor ON01210 (Ex-RAD), recombinant human interleukin-12 (HemaMax), beclomethasone (OrbeShield), and a granulocyte colony-stimulating factor (G-CSF, Neupogen). Ondansetron hydrochloride dihydrate (Latran) was registered as an antiemetic drug for prevention and therapy of the primary response to radiation in Russia, and granisetron (Kytril) was registered as an antiemetic drug upon irradiation abroad. Potassium iodide, potassium ferric hexacyanoferrate (Ferrocin), diethylenetriaminepentaacetate calcium trisodium (Pentacin, calcium trisodium pentetate), and 2,3-dimercaptopropansulfonate sodium (Unithiol) are used in Russia for the prevention and treatment of damage from irradiation via incorporated radionuclides. Potassium iodide (ThyroShield), diethylenetriaminepentaacetate zinc trisodium (Zn-DTPA, Pentetate zinc trisodium), diethylenetriaminepentaacetate calcium trisodium (Ca-DTPA, Pentetate calcium trisodium), and ferric hexacyanoferrate (Prussian blue, Radiogardase) are used as decorporation agents abroad. Cytokines, vitamins, low-molecular compounds, inhibitors of apoptosis, etc., are considered promising means for the prevention and early treatment of radiation damage.

The aim of this study was to investigate the mean survival time for Chernobyl clean-up workers (liquidators) with diagnosed solid cancer. The cohort of liquidators contained 142 871 males who worked in the Chernobyl exclusion zone from 1986–1987. Individual medical and dosimetry information collected during the follow-up period from 1991 up to 2015 was used in the study. The number of liquidators cases with documented stages of the disease was 7652, the number of overall death cases among those liquidators was 5085 (4351 deaths were due to cancer). Mean survival time for liquidators after the diagnosis of solid cancer (ICD-10: C00-C80.9) and documented tumor stages between 2000 over 2015 was 4.73 years. For tumors of respiratory organs (ICD-10: C30-C39.9), the mean survival time was 2.57 years; for tumors of digestive organs (ICD-10: C15-C26.9), 3.55 years. The mean survival time for liquidators with a documented diagnosis of cancer was continuously increasing despite the cohort aging and the increase of total mortality. The relationship between the mean survival time and tumor stage was studied. The dependence of the mean survival time on the stage of the tumor was investigated. The survival time, when changing from the 1st stage to the 4th stage, decreased seven times (from 8.62 to 1.22 years). The relationship between the mean survival time and radiation dose received by a liquidator was studied. Two dose groups were identified: group 0–100 mGy (average dose: 56.6 mGy) and group 100+ mGy (average dose: 187.9 mGy). Mean survival time was 4.66 and 4.72 years and the difference between the values was insignificant. Studies carried out in the cohort with varying size and age provided actual estimates of the effects of technological factors on health of certain human populations and groups.

It has been shown for the first time that preliminary incubation of bacteria in a medium containing deuterium oxide (D₂O) at concentrations of 2.5 to 10% leads to an increase in recA expression induced by hydrogen peroxide at concentrations of 2.2–8.8 mmol/L. The induction of recA in deuterated and non-deuterated (control) cultures was compared using a biosensor based on the E. coli strain K12 MG1655 (pRecA-lux), where luminescence occurs as a result of recA promoter activation in response to DNA damage caused by H₂O₂. The most effective D₂O concentrations were 5.0 and 7.5%. To explain the phenomenon, expression of the catalase gene was studied in deuterated and non-deuterated cultures of E. coli K12 MG1655 (pKatG-lux) biosensor. The luminescence of this biosensor results from activation of the katG promoter in response to an increase in the concentration of H₂O₂ in the cell. It was found that D₂O downregulated katG expression, which can lead to H₂O₂ accumulation, and, as a consequence, to an increase in the level of DNA damage as seen by an increase in recA expression.