What is Known and Objective Many investigators agree that appropriate rational utilization of therapeutic drug monitoring (TDM) with Bayesian feedback dosage adjustment facilitates epilepsy treatment with carbamazepines and/or valproates by increasing the seizure control and safety, as well as by reducing treatment costs. In previous works we have developed and used in clinical practice population pharmacokinetic (PK) models of different dosage forms for valproate (VPA) and post – induction carbamazepine (CBZ) behaviour as well as for combined therapy with CBZ plus another “old” antiepileptic drug (AED). An important step of external validation is to evaluate how well a procedure of Bayesian individualizing AED dosage regimens based on a proposed population PK model and sparse TDM data “works”, and how helpful it is in real practical clinical settings. The aim of this study was to evaluate the predictability of individualized dosage regimens for monotherapy with CBZ in the post-induction period or with VPA, as well as for CBZ and VPA given as combination therapy based on TDM data of epileptic patients and the earlier developed population models. Methods Four groups of TDM data were analyzed using the USC*PACK software for PK/PD analysis: 556 predictions for adult epileptic patients on CBZ monotherapy, 662 predictions for VPA monotherapy, 402 predictions of CBZ serum levels and 430 predictions of VPA serum levels for adult epileptic patients on CBZ+VPA combination therapy. Statistical characteristics of the prediction errors and weighted prediction errors were used to estimate bias and precision of predictions. Intraindividual and interoccasional variability of predictions were also estimated. Results and Discussion This study demonstrated that in most cases of CBZ and VPA monotherapy and combination therapy, predictions of future AED concentrations based on the earlier developed population PK models, TDM data and patient-specific maximum aposteriori probability (MAP) Bayesian posterior parameter values provided clinically acceptable estimates. Statistical analysis of the residuals demonstrated that the distributions of residuals and weighted residuals were close to a Normal distribution (Kolmogorov – Smirnov test, p>0.05) and their mean values did not differ statistically significantly from zero (no statistically significant bias, p>0.05) for all groups of predictions. The observed decreased quality of predictions of VPA concentrations during VPA+CBZ combination therapy, especially when CBZ dosages were changed, might well be explained by their PK interactions. For all groups, in linear regression analysis, the observed trend of decreasing of the prediction quality over various future prediction time horizons was considered statistically significant (p<0.05). Prediction of serum levels further into the future was less precise than those closer to the present for a 1.5 to 3.5-year observation period. No bias in predictions was associated with the time horizons. What is New and Conclusion Our validation res...

The following paper deals with the complexes of the late (Levshin) stage of the Kama culture and the early Eneolithic ceramic complexes of the Novoilyinskaya culture of the Middle Prikamye within the framework of a historical-cultural approach to the study of pottery. In the course of the work, the most stable traditions of raw material selection were highlighted: silty clay was used for the Kama culture; clay and silty clay were used in equal shares for the manufacture of Novoilyinskaya ceramics. For the manufacture of Kama ceramics raw materials were initially dried and crushed; this tradition was absent in the Novoilyinskaya culture. In both cultures mostly unsprayed (ductile) raw materials were used. As a result, it turned out that the population of the Kama region of the early Eneolithic was formed on the basis of the genesis of the local Neolithic population - the Kama culture representatives with the new (Volga) population. This fact may be indicated by differences in the skills of preparing plastic raw materials, mineral impurities for the preparation of the molding material, as well as the methods of applying the ornament.

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The paper analyzes a complex of ceramics of the Volosovskaya culture of the Ozymenki II parking lot located in Primokshan within the framework of a typological and historical-cultural approach to the study of pottery. Previously, the authors published the Neolithic materials of this monument; this work is devoted to the Eneolithic ware. In the course of the study, the most stable forms of corollas, ornamental elements and ornamental motifs were identified. To carry out a technical and technological analysis, the Volosovskaya ceramics were divided into groups according to the characteristic elements of the ornament. The tradition of selecting raw materials characteristic of all Eneolithic ceramics of the site was highlighted: the predominant use of plastic (unpeeled) silty clay in a naturally moistened state. Recipes of the molding mass are also recorded, which demonstrate a variety of options: MC + FB + OS, MC + FB + C + OS, IPRM + C + OS, MC + CS + C + OS, MC + OS, MC + FB. According to the results of the study, the authors concluded that the materials of this monument should be attributed to the middle stage of the Volosovskaya culture, since there is a combination of dishes without ornament and dense ornamentation, a weakly profiled form of vessels prevails, there are no L-shaped corollas.