FISHBURNE's METHOD AND THE CLASSICAL METHOD OF PHARMACOECONOMIC ANALYSIS IN THE EVALUATION OF ANTIBIOTIC TREATMENT OF ACUTE AND RECURRENT BRONCHITIS IN CHILDREN

Objective: This study was performed in order to estimate clinical effectiveness of antibiotic therapy in acute and recurrent obstructive bronchitis. For estimation the following was used: the Fishbern method of antibiotics distribution according to clinical effectiveness levels with the help of weighted coefficients and classical cost–efficiency†pharmacoeconomic analysis of the given antibiotic therapy. Then, for the first time ever, the obtained results of both methods were combined.Methods: Materials were presented by the data on antibiotic therapy, given for patients who were hospitalized to the in-patient medical facilities due to acute or recurrent obstructive bronchitis. Medical records of 2 259 patients were included in the study. The patients were 0 to 18 y old. In order to determine the weighed coefficients of each used antibiotic with subsequent distribution according to the levels of clinical effectiveness the Fishbern method was applied. Three levels of clinical effectiveness were used in this study, i.e. high, medium and low. The cost–efficiency†pharmacoeconomic analysis was applied to combine costs and efficiency of the compared therapy courses in acute and recurrent obstructive bronchitis.Results: Finally we found out that the highest probability of positive effect of cephalosporins group agents was associated with the use of Cefotaximum. (Biosynthesis). From the pharmacoeconomic point of view the most effective in treating acute and recurrent obstructive bronchitis in children in the in-patient facilities was Ceftriaxonum (Synthesis). Out of protected penicillins group, we used Amoxicillin/clavulanic acid–original drug Augmentin (Smithkline Beecham Pharmaceuticals) and generic drug Amoxiclav (Lek d. d). Augmentin effectiveness was 0.591, and Amoxiclav effectiveness–0.530. Cost of Augmentin treatment course was 106.26 rub. (1.68 US$), cost of Amoxiclav treatment course–103.50 rub.(1.63 US$). Augmentin use turned out to be the most reasonable. Augmentin treatment course was characterized by lower ICER coefficient versus Amoxiclav. We found out that from the pharmacoeconomic point of view Azitromicin (Vertex Ltd.) treatment turned out to be the most reasonable of the whole macrolides antibiotics for treatment of acute and recurrent obstructive bronchitis. However, according to the Fishbern clinical effectiveness classification this antibiotic belonged to the group with medium effectiveness level. The group with high effectiveness level included Sumamed, Azitral, Hemomicin, Clacid, Zitrocin and Clabax. Clacid and Clabax were excluded during the pharmacoeconomic analysis. The highest value of ICER coefficient was obtained for Sumamed and made up 39,367.50 rub. (621.53 US$). The highest level of clinical effectiveness was characteristic for Sumamed as well. Besides Sumamed was an original drug of azitromicin. According to the obtained data Azitral and Hemomicin had the lowest values of ICER coefficient (1151.67 rub. (18.18 US$) and 1812.22 rub. (28.61 US$) respectively). Therefore based on the clinical economic analysis these medical agents turned out to be the most suitable.Conclusion: The results of the pharmacoeconomic analysis showed that the most effective drugs in treatment of acute and recurrent obstructive bronchitis in children in in-patient facilities appeared to be the following: out of cephalosporins-Ceftriaxonum (Synthesis), out of protected penicillins-Augmentin (Smithkline Beecham Pharmaceuticals), out of macrolides-Azitromicin (Vertex Ltd.). According to the Fishbern classification, these drugs belonged to the group with medium level of effectiveness.Â

ROLE OF "ATYPICAL" MICROORGANISMS ON THE FORMATION OF BRONCHIAL ASTHMA IN CHILDREN WITH ACUTE AND RECURRENT OBSTRUCTIVE BRONCHITIS

Objective: This study was undertaken to determine the link between the presence of atypical†infections in patients with acute obstructive andrecurrent obstructive bronchitis (AOB/ROB) and bronchial asthma (BA) development based on the concept of risk.Methods: The materials for the study were the data records of patients hospitalized with AOB or ROB and whose analysis was performed to identifyantibodies to atypical†microflora (796 patients). The study period was 4 years from 2008 to 2011. In the analyzed period, immunosorbent assay forthe detection of antibodies to atypical†microflora (Chlamydophila pneumoniae, Mycoplasma pneumoniae, Mycoplasma hominis) was performed. Theconcept of risk identification was based on the determination of the absolute risk, attributable risk (AtR), relative risk, population attributable risk, aswell as on the definition of the standard errors for each type of risk and the confidence interval.Results and Conclusion: Methodical aspects of determining the relationship between the presence of atypical†infections in patients with AOBor ROB and BA development were based on the concept of risk. The analysis showed a direct link between the increase of cases of BA formationagainst the backdrop of atypical†infections. Therefore, the performed analysis of atypical pathogens influences on BA occurrence in patients withAOB/ROB which indicates direct dependence increase of BA incidence on atypical infection. In experimental group, Frequency of event is 14.84% inexperimental group. Frequency of event is 1.67% in control group. The risk factor increases probability of event by 13.17%, the risk factor increasesprobability of event by 13.17%. Presence of atypical infection leads to increase of BA incidence by 8.9 times. Number needed to harm (NNH) is 7.59,i.e., in the presence of atypical infection in patients with AOB/ROB, each eighth exposed person develops BA in addition to background level of BAincidence.Keywords: Acute obstructive bronchitis, Recurrent obstructive bronchitis, Bronchial asthma, The concept of risk, Risk factor, The absolute risk,Relative risk, Attributable risk, Population attributable risk, Number needed to harm

Mechanical Properties of Glass Fiber Composites Reinforced by Textile Fabric

Interest to structural application of textile reinforced polymer matrix composite materials (CM) is growing during last years. In different branches of machine building, aerospace, automotive and others industries we can find structural elements preferably be produced using such reinforcement. At the same time, such materials are exhibiting elastic and strength properties scatter. In the framework of the present investigation, we observe yarn penetrated by a resin in a composite as a reinforcing “macro” fiber. Such “macro” fiber mechanical properties were measured experimentally, for this purpose was produced and was tested by tension until fracture fiber samples, having different length. Then was elaborated and was realized structural strength probabilistic model. In the textile geometry, was picked out repeating structural element – polymer matrix volume with two curved “macro” fiber’s chunks inside it. Complete composite material volume is possible to represent as a set of repeating structural elements. External loads application leads to disperse structural elements failure. Neighboring to ruptured elements are overloaded leading to higher probability to fail for them. Using FEM was modeled stress state in “macro” fibers inside CM. Then, was numerically obtained stress distribution in composite material, having different number of broken loops. Probabilities of different numbers of failed elements were calculated.  Strength probability function, based on Weibull approach was obtained. CM samples were tested under tension and obtained results were compared with numerical modeling as well as were analyzed

Fluctuating Nonlinear Spring Model of Mechanical Deformation of Biological Particles

We present a new theory for modeling forced indentation spectral lineshapes of biological particles, which considers non-linear Hertzian deformation due to an indenter-particle physical contact and bending deformations of curved beams modeling the particle structure. The bending of beams beyond the critical point triggers the particle dynamic transition to the collapsed state, an extreme event leading to the catastrophic force drop as observed in the force (F)-deformation (X) spectra. The theory interprets fine features of the spectra: the slope of the FX curves and the position of force-peak signal, in terms of mechanical characteristics --- the Young's moduli for Hertzian and bending deformations E_H and E_b, and the probability distribution of the maximum strength with the strength of the strongest beam F_b^* and the beams' failure rate m. The theory is applied to successfully characterize the $FX$ curves for spherical virus particles --- CCMV, TrV, and AdV

Unsupervised word embeddings capture latent knowledge from materials science literature.

The overwhelming majority of scientific knowledge is published as text, which is difficult to analyse by either traditional statistical analysis or modern machine learning methods. By contrast, the main source of machine-interpretable data for the materials research community has come from structured property databases1,2, which encompass only a small fraction of the knowledge present in the research literature. Beyond property values, publications contain valuable knowledge regarding the connections and relationships between data items as interpreted by the authors. To improve the identification and use of this knowledge, several studies have focused on the retrieval of information from scientific literature using supervised natural language processing3-10, which requires large hand-labelled datasets for training. Here we show that materials science knowledge present in the published literature can be efficiently encoded as information-dense word embeddings11-13 (vector representations of words) without human labelling or supervision. Without any explicit insertion of chemical knowledge, these embeddings capture complex materials science concepts such as the underlying structure of the periodic table and structure-property relationships in materials. Furthermore, we demonstrate that an unsupervised method can recommend materials for functional applications several years before their discovery. This suggests that latent knowledge regarding future discoveries is to a large extent embedded in past publications. Our findings highlight the possibility of extracting knowledge and relationships from the massive body of scientific literature in a collective manner, and point towards a generalized approach to the mining of scientific literature

Zooplankton and Dead Zooplankton in Kharbeyskie Lakes of Bolshezemelskaya Tundra (Period From 2009 to 2012)

В июле–августе 2009, 2010, 2012 гг. исследован состав и структура зоопланктона в системе Харбейских озер Большеземельской тундры. Обнаружено 87 видов и форм, из которых более половины коловратки (Rotifera). Планктонная фауна обследованных озер обычна для южных тундр и представлена азональными таксонами. Зоопланктон оз. Большой Харбей и придаточных озер различался по составу и количественным показателям, которые соответствовали различным уровням трофности экосистем. Межгодовая динамика планктонных сообществ в озерах была связана с динамикой погодных условий. Доминантный комплекс зоопланктона по численности в оз. Большой Харбей состоял из четырех, по биомассе – из девяти видов, был представлен эвпланктонными видами как коловраток, так и ракообразных (Cladocera, Copepoda) и слабо изменялся по годам. В небольших придаточных озерах число доминирующих в планктоне видов было меньшим по сравнению с оз. Большой Харбей, в глубоководных – доминантный комплекс был сходен с таковым в Большом Харбее. Не было выявлено достоверных различий в количестве зоопланктона в литорали и профундали основного озера системы. Пространственное распределение видов соответствовало морфологическим особенностям водоемов. В 2012 г. в основном и придаточных Харбейских озерах наблюдалась депрессия планктонных Copepoda, проявлявшаяся в высокой доле мертвых особей этих ракообразных в численности рачкового планктона. Наблюдали поражение микропаразитами (вероятно, грибковое) доминирующего вида – Heterocope appendiculata (Copepoda)Zooplankton composition and structure in Kharbeyskie Lakes system of Bolshezemelskaya tundra were investigated in July, August of 2009, 2010 and 2012. In total, 87 species and forms were found and more than half of them belonged to rotifers (Rotifera). Plankton fauna of the studied lakes was typical for southern tundra and presented by azonal taxa. Composition and abundance of zooplankton of Bolshoy Kharbey Lake and adjacent lakes were different and correspond to trophic conditions in ecosystems. Inter-annual dynamics of plankton communities in the lakes was determined by weather conditions. In Bolshoy Kharbey Lake four euplanktonic species of rotifers and crustaceans (Cladocera and Copepoda) dominated in terms of abundance and nine species dominated in terms of biomass. Inter-annual changes in dominant species composition were insignificant. In Bolshoy Kharbey Lake the number of dominant species were more than in the adjacent lakes. Differences in the abundance of zooplankton between littoral and prophundal zones of the main lake were not significant. Spatial distribution of species was determined by the morphology of the lakes. Depression of plankton copepods in the main and adjacent Kharbeyskie Lakes was observed in 2012 and proportion of dead individuals in crustacean communities was high. Probably it was related with mass infection of dominant species Heterocope appendiculata (Copepoda) by microparasite

Biogeographic patterns of planktonic and meiobenthic fauna diversity in inland waters of the Russian Arctic

Broad-scale assessment of biodiversity is needed for detection of future changes across substantial regions of the Arctic. Presently, there are large data and information gaps in species composition and richness of the freshwater planktonic and meiobenthos communities of the Russian Arctic. Analysis of these data is very important for identifying the spatial distribution and temporal changes in species richness and diversity of rotifers, cladocerans, and copepods in the continental Russian Arctic. We investigated biogeographic patterns of freshwater plankton and meiobenthos fromc. 67 degrees to 73 degrees N by analysing data over the period 1960-2017. These data include information on the composition of rotifers, cladocerans, and copepods obtained from planktonic and meiobenthic samples, as well as from subfossil remains in bottom sediments of seven regions from the Kola Peninsula in the west, to the Indigirka River Basin (east Siberia) in the east. Total richness included 175 species comprised of 49 rotifer genera, 81 species from 40 cladoceran genera, and 101 species from 42 genera of calanoid, cyclopoid, and harpacticoid copepods. Longitudinal trends in rotifer and micro-crustacean diversity were revealed by change in species composition from Europe to eastern Siberia. The most common and widespread species were 19 ubiquitous taxa that includedKellicottia longispina(Rotifera),Chydorus sphaericuss. lat. (Cladocera),Heterocope borealis,Acanthocyclops vernalis, andMoraria duthiei(Copepoda). The highest number of rare species was recorded in the well-studied region of the Bolshezemelskaya tundra and in the Putorana Plateau. The total number of copepod and rotifer species in both Arctic lakes and ponds tended to increase with latitude. Relative species richness of copepods was positively associated with waterbody area, elevation, and precipitation, while relative species richness of cladocerans was positively related to temperature. This result is consistent with known thermophilic characteristics of cladocerans and the cold tolerance properties of copepods, with the former being dominant in shallow, warmer waterbodies of some western regions, and the latter being dominant in large cold lakes and waterbodies of eastern regions. Rotifers showed a negative association with these factors. Alpha- and beta-diversity of zooplankton in the Russian Arctic were strongly related to waterbody type. Lake zooplankton communities were more diverse than those in pond and pool systems. Moreover, the highest beta-diversity values were observed in regions that showed a greater breadth in latitude and highly heterogeneous environmental conditions and waterbody types (Bolshezemelskaya tundra and Putorana Plateau). Redistribution of freshwater micro-fauna caused by human activities occurred in the 1990s and 2000s. As a result of climate warming, a few cladoceran species appear to have extended their range northward. Nevertheless, the rotifer and micro-crustacean fauna composition and diversity of the majority of Arctic regions generally remain temporally conservative, and spatial differences in composition and species richness are chiefly associated with the differences between the warmer European and colder east Siberian climates.Peer reviewe

Tubulin bond energies and microtubule biomechanics determined from nanoindentation in silico

Microtubules, the primary components of the chromosome segregation machinery, are stabilized by longitudinal and lateral non-covalent bonds between the tubulin subunits. However, the thermodynamics of these bonds and the microtubule physico-chemical properties are poorly understood. Here, we explore the biomechanics of microtubule polymers using multiscale computational modeling and nanoindentations in silico of a contiguous microtubule fragment. A close match between the simulated and experimental force-deformation spectra enabled us to correlate the microtubule biomechanics with dynamic structural transitions at the nanoscale. Our mechanical testing revealed that the compressed MT behaves as a system of rigid elements interconnected through a network of lateral and longitudinal elastic bonds. The initial regime of continuous elastic deformation of the microtubule is followed by the transition regime, during which the microtubule lattice undergoes discrete structural changes, which include first the reversible dissociation of lateral bonds followed by irreversible dissociation of the longitudinal bonds. We have determined the free energies of dissociation of the lateral (6.9+/-0.4 kcal/mol) and longitudinal (14.9+/-1.5 kcal/mol) tubulin-tubulin bonds. These values in conjunction with the large flexural rigidity of tubulin protofilaments obtained (18,000-26,000 pN*nm^2), support the idea that the disassembling microtubule is capable of generating a large mechanical force to move chromosomes during cell division. Our computational modeling offers a comprehensive quantitative platform to link molecular tubulin characteristics with the physiological behavior of microtubules. The developed in silico nanoindentation method provides a powerful tool for the exploration of biomechanical properties of other cytoskeletal and multiprotein assemblie