Мінливість дуже сильних дощів і сильних злив в Україні

Розглянуто міжрічну мінливість кількості випадків стихійних гідрометеорологічних явищ (СГЯ), а саме: дуже сильних дощів і сильних злив – в Україні та її регіонах у другій половині ХХ – на початку ХХІ ст. Використавши методи сезонної декомпозиції, встановлено тенденцію динаміки цих рядів протягом досліджуваного періоду. Шляхом автокореляційного та спектрального аналізів визначено циклічні компоненти у структурі рядів річної кількості випадків СГЯ та їх особливості в періоди, коли спостерігали тенденцію до зменшення і збільшення інтенсивності цих явищ.Рассмотрена межгодовая изменчивость количества случаев очень сильных дождей и сильных ливней в Украине и ее регионах во второй половине ХХ - в начале ХХІ в. Установлена тенденция динамики этих рядов на протяжении исследуемого периода. Определены циклические компоненты в структуре рядов годового количества случаев стихийных осадков (СГЯ) и их особенности в периоды, когда наблюдали тенденцию к уменьшению и увеличению интенсивности этих явлений

Адаптація в українській термінології іншомовних лексем на позначення засобів розміщення туристів

Розглянуто шляхи та причини запозичення іншомовної лексики на позначення засобів розміщення туристів, подано значення окремих запозичених лексем.The article studies the ways and reasons for lexical units denoting tourist accommodation borrowing. The meanings of some borrowed terms are given

An adverse outcome pathway framework for neural tube and axial defects mediated by modulation of retinoic acid homeostasis

Developmental toxicity can be caused through a multitude of mechanisms and can therefore not be captured through a single simple mechanistic paradigm. However, it may be possible to define a selected group of overarching mechanisms that might allow detection of the vast majority of developmental toxicants. Against this background, we have explored the usefulness of retinoic acid mediated regulation of neural tube and axial patterning as a general mechanism that, when perturbed, may result in manifestations of developmental toxicity that may cover a large part of malformations known to occur in experimental animals and in man. Through a literature survey, we have identified key genes in the regulation of retinoic acid homeostasis, as well as marker genes of neural tube and axial patterning, that may be used to detect developmental toxicants in in vitro systems. A retinoic acid-neural tube/axial patterning adverse outcome pathway (RA-NTA AOP) framework was designed. The framework was tested against existing data of flusilazole exposure in the rat whole embryo culture, the zebrafish embryotoxicity test, and the embryonic stem cell test. Flusilazole is known to interact with retinoic acid homeostasis, and induced common and unique NTA marker gene changes in the three test systems. Flusilazole-induced changes were similar in directionality to gene expression responses after retinoic acid exposure. It is suggested that the RA-NTA framework may provide a general tool to define mechanistic pathways and biomarkers of developmental toxicity that may be used in alternative in vitro assays for the detection of embryotoxic compounds. (C) 2014 Elsevier Inc. All rights reserved

Evaluation of polygenic risk models using multiple performance measures: a critical assessment of discordant results

Purpose: The area under the receiver operating characteristic curve (AUC) is commonly used for evaluating the improvement of polygenic risk models and increasingly assessed together with the net reclassification improvement (NRI) and integrated discrimination improvement (IDI). We evaluated how researchers described and interpreted AUC, NRI, and IDI when simultaneously assessed. Methods: We reviewed how researchers described definitions of AUC, NRI, and IDI and how they computed each metric. Next, we reviewed how the increment in AUC, NRI, and IDI were interpreted, and how the overall conclusion about the improvement of the risk model was reached. Results: AUC, NRI, and IDI were correctly defined in 63, 70, and 0% of the articles. All statistically significant values and almost half of the nonsignificant were interpreted as indicative of improvement, irrespective of the values of the metrics. Also, small, nonsignificant changes in the AUC were interpreted as indication of improvement when NRI and IDI were statistically significant. Conclusion: Researchers have insufficient knowledge about how to interpret the various metrics for the assessment of the predictive performance of polygenic risk models and rely on the statistical significance for their interpretation. A better understanding is needed to achieve more meaningful interpretation of polygenic prediction studies

A statistical approach towards the derivation of predictive gene sets for potency ranking of chemicals in the mouse embryonic stem cell test

The embryonic stem cell test (EST) is applied as a model system for detection of embryotoxicants. The application of transcriptomics allows a more detailed effect assessment compared to the morphological endpoint. Genes involved in cell differentiation, modulated by chemical exposures, may be useful as biomarkers of developmental toxicity. We describe a statistical approach to obtain a predictive gene set for toxicity potency ranking of compounds within one class. This resulted in a gene set based on differential gene expression across concentration-response series of phthalatic monoesters. We determined the concentration at which gene expression was changed at least 1.5-fold. Genes responding with the same potency ranking in vitro and in vivo embryotoxicity were selected. A leave-one-out cross-validation showed that the relative potency of each phthalate was always predicted correctly. The classical morphological 50% effect level (ID50) in EST was similar to the predicted concentration using gene set expression responses. A general down-regulation of development-related genes and up-regulation of cell-cycle related genes was observed, reminiscent of the differentiation inhibition in EST. This study illustrates the feasibility of applying dedicated gene set selections as biomarkers for developmental toxicity potency ranking on the basis of in vitro testing in the EST

Developmental immunotoxicity testing of 4-methyl anisole

The developmental immunotoxicity of 4-methyl anisole (4MA) was investigated in the rat. Four study designs were used, with either premating or post-weaning onset of exposure, continued to postnatal day 50, and with or without additional oral gavage of pups from postnatal day 10 onward. Reduced litter size (benchmark dose lower confidence limit (BMDL) 80 mg/kg bw/day) was the most sensitive developmental parameter, with pup relative organ weight effects observed at similar BMDLs, in the absence of maternal toxicity. Eosinophil numbers were reduced at lower doses (BMDL 16 mg/kg bw/day). KLH challenge resulted in increased IL-13 and TNF-alpha responses, and variably reduced IgG production (BMDL 27 mg/kg bw/day). T-4 levels were reduced by 11% at maximum with a BMDL of 73 mg/kg bw/day. Differences between exposure cohorts were limited and were considered to be without biological significance. This study shows that 4MA induces developmental immunotoxicity at doses below those inducing developmental and general toxicity. These observations being independent of the study designs applied suggest that the post-weaning period, included in all designs, is the most relevant sensitive period for inducing 4MA mediated developmental immunotoxicity. Moreover, this study stresses the importance of including developmental immunotoxicity testing by default in regulatory toxicology. (C) 2015 Elsevier Inc. All rights reserved

Developmental immunotoxicity of di-n-octyltin dichloride (DOTC) in an extended one-generation reproductive toxicity study

Developmental immunotoxicity assessment is considered ready for inclusion in developmental toxicity studies. Further evaluation of proposed and additional assays is needed to determine their utility in assessing developmental immunotoxicity. In this study, a wide range of immunological parameters was included in an extended one-generation reproductive toxicity protocol. F0 Wistar rats were exposed to DOTC via the feed (0, 3, 10, and 30mg/kg) during pre-mating, mating, gestation and lactation and subsequently F1 were exposed from weaning until sacrifice. Immune assessments by several immune parameters were performed at PNDs 21, 42 and 70. The T cell-dependent antibody response to Keyhole Limpet hemocyanin (KLH) was assessed following subcutaneous immunizations with KLH on PNDs 21 and 35 and the delayed-type hypersensitivity response (DTH) against KLH was evaluated at PND 49. No effects were found on PND 21. While effects on lymphocyte subpopulations in the thymus were only observed in the 30. mg/kg group on PND 42, effects on lymphocyte subpopulations in the spleen were found in the 30. mg/kg group on both PNDs 42 and 70. The DTH response already showed an effect at 3. mg/kg and was the overall critical endpoint. The results from this study support the inclusion of splenocyte subpopulation parameters in developmental toxicity studies and identified the DTH response as an important functional parameter. © 2011 Elsevier Ireland Ltd

Developmental immunotoxicity in male rats after juvenile exposure to di-n-octyltin dichloride (DOTC)

To determine relevant endpoints for evaluating developmental immunotoxicity due to juvenile exposure and optimal age of the animals at assessment, a wide range of immunological parameters were assessed in a juvenile toxicity study. Rats were exposed to di-n-octyltin dichloride (DOTC) by gavage from postnatal day (PND) 10 through PND 21 and via the diet after weaning using a benchmark dose (BMD) approach. Immune assessments were performed in male rats on PNDs 21, 42, and 70 and a subset of animals was used to evaluate the T-cell dependent antibody response (TDAR) to Keyhole limpet hemocyanin. Immune effects were more pronounced on PND 21 and 42 and observed at lower doses than developmental effects. The most sensitive immune parameters affected included TDAR parameters and thymocyte subpopulations with lower confidence limits of the benchmark doses (BMDLs) below the overall no-observed-adverse-effect-level (NOAEL) for DOTC reported so far in literature. These findings illustrate the relative sensitivity of the developing immune system for DOTC, the additional value of assessing functional immune parameters, and underscore the relevance of juvenile immunotoxicity testing in view of the risk assessment of chemicals