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Summary Subject and purpose of work: The article describes a new subject of research into the history of economic thought, the international Pribuzhie region. The article discusses the history of the rise and development of economic science in the Pribuzhie region from the 8th to the 21st century, which is the subject of research. The aim of the article is to present a new perspective on the subject of research as well as the characteristics of the process of economic science in the Pribuzhie region. Materials and methods: The article uses a conventional method, which is a collection of historical, philosophical and economic methods of cognition, on the basis of which, in the context of a scientific program, the past of economic thought and relevant doctrines are examined, and their content is described. Results: The various historical stages in the development of the economic thought of the Pribuzhie region are described, as well as new, unpublished facts relating to individual economic doctrines. Conclusions: Political activity and public administration activities should involve economic education, which defines the essence of economic policy, its objectives and ways of realization in the practical sphere.

Abstract Background Despite its importance, there is no agreed definition of recovery of ambulation in dogs with spinal cord injury. Objectives To validate a new walking test in dogs recovering from thoracolumbar spinal cord injury. Animals Two hundred twenty‐four dogs weighing

Fuzzy numbers are often used for modeling imprecise perceptions of the real-valued observations. Such epistemic fuzzy data may cause problems in statistical reasoning and data analysis. We propose a universal nonparametric technique, called the epistemic bootstrap, which could be helpful when the existing methods do not work or do not give satisfactory results. Besides the simple epistemic bootstrap, we develop its several refinements that aim to reduce the variance in statistical inference. We also perform an extended simulation study to examine statistical properties of the approaches considered. The discussion of the results is supplemented by some hints for practical use.

Strategic ambiguity, or the deliberate policy of uncertainty as to whether the United States would use force to defend Taiwan against an invasion by the People's Republic of China, has been the centrepiece of US policy towards the Taiwan issue for decades. This paper discusses the factors driving the redefinition of strategic ambiguity and its recalibration throughout Donald Trump's presidency (2017–2021). The fundamental driver of this change was to balance the rising power of the People’s Republic of China (PRC). The paper applied offensive realism as a theoretical framework for its analysis. Under President Donald Trump, Washington modified its policy of strategic ambiguity, explicitly framing relations with Taiwan within a broader Indo-Pacific strategy. While the US retained key elements of strategic ambiguity, including the 'One China' policy, it added new features to deploy it offensively against Beijing's growing regional hegemony. The increased dynamism and unpredictability of relations with Taiwan were matched by a welcoming attitude towards strengthening Taiwanese identity and highlighting the systemic differences between communist China and democratic Taiwan. America stepped up arms sales and encouraged Taiwan to build its self-defence capabilities. Washington engaged in countering Chinese attempts to isolate Taiwan internationally and included it in restructuring global supply chains. Although the United States has not formally revised the boundaries of the 'One China' policy, the modification of strategic ambiguity increased Taiwan's prominence in US-China power competition and pushed back the prospect of peaceful unification.

Background: Allergic rhinitis (AR) is the most common type of rhinitis, the treatment of which relies on relieving symptoms. Therefore, we aimed to assess the criteria that influence doctors' decision-making in the process of drug selection for the treatment of allergic rhinitis based on quantitative, qualitative, and cost analyses. Methods: We conducted a survey study with the participation of 300 allergologists. A self-developed questionnaire was presented during a computer-assisted telephone interview (CATI) according to standard procedures. The contingency table underwent statistical analysis using the chi-square test with Cramer's V. Results were considered statistically significant at p < 0.05. Results: Our analyses showed that doctors most often prescribe intranasal glucocorticoids and oral antihistamines to treat allergic rhinitis in patients of all ages. The most common factor that affects the decision-making related to AR treatment was the efficiency of the drug. We found a significant relationship between factors and the main workplace (X-squared = 122.81, df = 90, p -value = 0.0123, Cramer's V = 0.1787216), as well as voivodeship of the main workplace (X-squared = 440.75, df = 270, p -value = 2.378e-10, Cramer's V = 0.1954731). In our study, respondents claimed that patients are willing to pay 31–50 PLN (∼€7- €11) monthly for the treatment of mild and moderate forms of AR, while they were willing to pay 51–100 PLN (∼€11–€22) for treatment of the severe AR form. Conclusion: Our study confirms that the management of AR should be focused on the patient. One of the most important factors in choosing a drug is its effectiveness. Moreover, an important factor in the effective treatment of AR is the financial issue; as shown in our analysis, AR treatment costs can be a significant burden, especially for less wealthy citizens in Poland. [ABSTRACT FROM AUTHOR]

The cytochrome P450 2D6 (CYP2D6) is a key xenobiotic-metabolizing enzyme involved in the clearance of many drugs. Genetic polymorphisms in CYP2D6 contribute to the large inter-individual variability in drug metabolism and could affect metabolic phenotyping of CYP2D6 probe substances such as dextromethorphan (DXM). To study this question, we (i) established an extensive pharmacokinetics dataset for DXM; and (ii) developed and validated a physiologically based pharmacokinetic (PBPK) model of DXM and its metabolites dextrorphan (DXO) and dextrorphan O-glucuronide (DXO-Glu) based on the data. Drug-gene interactions (DGI) were introduced by accounting for changes in CYP2D6 enzyme kinetics depending on activity score (AS), which in combination with AS for individual polymorphisms allowed us to model CYP2D6 gene variants. Variability in CYP3A4 and CYP2D6 activity was modeled based on in vitro data from human liver microsomes. Model predictions are in very good agreement with pharmacokinetics data for CYP2D6 polymorphisms, CYP2D6 activity as described by the AS system, and CYP2D6 metabolic phenotypes (UM, EM, IM, PM). The model was applied to investigate the genotype-phenotype association and the role of CYP2D6 polymorphisms for metabolic phenotyping using the urinary cumulative metabolic ratio (UCMR), DXM/(DXO + DXO-Glu). The effect of parameters on UCMR was studied via sensitivity analysis. Model predictions indicate very good robustness against the intervention protocol (i.e. application form, dosing amount, dissolution rate, and sampling time) and good robustness against physiological variation. The model is capable of estimating the UCMR dispersion within and across populations depending on activity scores. Moreover, the distribution of UCMR and the risk of genotype-phenotype mismatch could be estimated for populations with known CYP2D6 genotype frequencies. The model can be applied for individual prediction of UCMR and metabolic phenotype based on CYP2D6 genotype. Both, model and database are freely available for reuse.