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Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P

This paper describes the technology and organization of the production of works on waterproofing the joints of highly prefabricated coating panels on a soft roof. The process of manufacturing waterproofing works can be divided into three stages - preparatory, main and final ones. Each stage has its own technological features and rules for performing work. The quality of execution of each stage affects the quality of work as a whole, ultimately providing the necessary reliability and strength of the coating.

As of the end of 2017, in Moscow, there are 286 mapped five-story fully-assembled residential buildings of K-7, II-32, II-35, 1605-AM, 1MG-300 series with total area of 1046,7 thousand square meters. They were built at the beginning of the era of mass construction, in 1959 - 1962 years, and were distinguished by thin outer walls of lightweight ribbed expanded clay panels with unstable thermal protection properties. The technologies used in the construction of such buildings do not allow reconstructing them. Nowadays, the task of demolition of the neighborhood of five-storey houses in Moscow with the maximum possible reduction in terms of production of works and the maximum quality of work is very important. It is also necessary to ensure safe work and compliance with all sanitary standards. The order of execution of the works has a mathematical solution method. It identifies issues that arise in the alternating sections performing the process of demolition.

The use of virtual structures in the area of CAD may have an impact on the design labour coefficient and on the works cost reduction. When developing and further functioning of virtual structures in organization, there are a number of issues related to the employees search and employment, work with CAD, with staff, payment for activities, acquisition and storage of information, reporting, interaction between the virtual team members, etc. The full activity of project organizations, both within the large and independent companies, requires for new procedural developments based on the information systems. The procedure of virtual structures development and implementation in organization is proposed to resolve this issue.

The article looks into virtual units of construction design companies. Challenges in virtual organization of construction design are discussed. Modern society is characterized by transition to informational model of organization. Also, we can talk about environmental engineering, that is, to improve the quality of information environment. New forms of organization can be classified according to such characteristics as scope and nature of the activity, type of ownership, legal status, and size. These forms, along with the virtual organization, include financial and industrial groups, business unions, and clusters. It is accepted to highlight main advantages of virtual organizations in the free choice of high-class resources while reducing time costs.

At the present time we consider the construction operations development triggered by the modern technologies development. The electronics, robotics, artificial intelligence, wireless technologies and more became the present-day production attribute. The creation of virtual organizations has become the expected solution of business communities. Following in the footsteps of information boom, in this article we consider the problem of construction field virtualisation, in particular: characteristics of virtuality and virtual structures operation, in-virtual organization work peculiarities, difficulties faced by the company manager with such form of work and criteria for the assessment of organization efficiency. The virtual organization is deemed to be the voluntary cooperation form of partners, aimed at project work type. This is the unique team, the basic resources of which are time and technologies. In general such organization does not have any geographical origin and it works using the Internet. In the context given herein, the virtual structure is considered in CAD conditions that is based on the high degree of construction field IT. Specific relations between the employees make the impact on the work process, therefore a number of both subjective (social, individual, etc.) and objective (financial) indices are given.

A review of the current state of the theory and practice of bioenergy production from waste allowed us to identify the scientific and applied problem of substantiating the rational configuration of a modular anaerobic bioenergy system, taking into account the volume of organic waste generated in settlements. To solve this problem, this paper develops an approach and an algorithm for matching the configuration of a modular anaerobic bioenergy production system with the amount of organic waste generated in residential areas. Unlike the existing tools, this takes into account the peculiarities of residential areas, which is the basis for accurate forecasting of organic waste generation and, accordingly, determining the configuration of the bioenergy production system. In addition, for each of the scenarios, the anaerobic digestion process is modeled, which allows us to determine the functional indicators that underlie the determination of a rational configuration in terms of cost and environmental performance. Based on the use of the developed tools for the production conditions of the Golosko residential area, Lviv (Ukraine), possible scenarios for the installation of modular anaerobic bioenergy production systems are substantiated. It was found that the greatest annual benefits are obtained from the processing of mixed food and yard waste. The payback period of investments in modular anaerobic bioenergy production systems for given conditions of a residential area largely depends on their configuration and ranges from 3.3 to 8.4 years, which differ from each other by 2.5 times. This indicates that the developed toolkit is of practical value, as it allows the coordination of the rational configuration of modular anaerobic bioenergy production systems with real production conditions. In the future, it is recommended to use the proposed decision support system to model the use of biomass as an energy resource in residential areas, which ensures the determination of the rational configuration of a modular anaerobic bioenergy production system for given conditions.

The modern system of national education, developing in the competence paradigm, puts on the agenda the need to form students' communicative skills that belong to the category of critical competencies of a meta-subject nature. The article discusses the methodological features and pedagogical conditions for forming meta-subject skills of schoolchildren in foreign language lessons. An attempt is proposed to determine the characteristics of the meta-subject approach, including a complex of personality traits that allow the student to act in a given communication situation at the level determined by the age-related psychological characteristics and the possibilities of the social experience of a younger student. The authors used the following research methods: utilizing the study and generalization of pedagogical experience and the survey method, the communicative, regulatory - behavioral and motivational characteristics of a younger student, which must be taken into account when introducing pedagogical technologies focused on meta-subject results in foreign language lessons, are concretized. The analysis of the real practice of an educational activity is aimed at establishing a set of features of the pedagogical support of the meta subject approach within the framework of the "foreign language" discipline in primary school. Based on the analysis of scientific literature on research and practical experience, several strategies have been identified that ensure the effective implementation of meta-subject results in younger students in foreign language lessons.

Both peripheral neuropathy and depression can be viewed as neurodegeneration's consequences of diabetes, at least in part coexisting with or resulting from sodium-calcium dysbalance. This study aims to assess the therapeutic potential of the orally applied reverse-mode inhibitor of the sodium-calcium exchanger (NCX) KB-R7943 in the streptozotocin (STZ) diabetes model in rats. A pilot pharmacokinetic (PK) study with high-performance liquid chromatography with high-resolution tandem mass spectrometric detection revealed higher drug exposure (AUC), lower volume of distribution (Vd) and clearance (Cl), and faster decline of the plasma concentration (ƛ) in rats with diabetes vs. controls. Brain and heart accumulation and urinary excretion of the unmetabolized KB-R7943 at least 24 h were also demonstrated in all rats. However, heart and hippocampus KB-R7943 penetration (AUCtissue/AUCplasma) was higher in controls vs. diabetic rats. The development of thermal, mechanical, and chemical-induced allodynia was assessed with the Cold plate test (CPT), Randall-Stiletto (R–S) test, and 0.5% formalin test (FT). Amitriptyline 10 mg/kg, KB-R7943 5 mg/kg, or 10 mg/kg p.o once daily was applied from the 28th to the 49th day. The body weight, coat status, CPT, R–S, and FT were evaluated on days (−5), 0, and 42. On day 41, a forced swim test and 24-h spontaneous physical activities were assessed. The chronic treatment effects were calculated as % of the maximum. A dose-depended amelioration of neuropathic and depression-like effects was demonstrated. The oral application of KB-R7943 for potentially treating neurodegenerative consequences of diabetes merits further studies. The brain, heart, and kidneys are essential contributors to the PKs of this drug, and their safety involvement needs to be further characterized.

BackgroundThe origin of sex differences in prevalence and presentation of neuropsychiatric and behavioral traits is largely unknown. Given established genetic contributions and correlations, we tested for a sex-differentiated genetic architecture within and between traits.MethodsUsing European ancestry genome-wide association summary statistics for 20 neuropsychiatric and behavioral traits, we tested for sex differences in single nucleotide polymorphism (SNP)-based heritability and genetic correlation (rg < 1). For each trait, we computed per-SNP z scores from sex-stratified regression coefficients and identified genes with sex-differentiated effects using a gene-based approach. We calculated correlation coefficients between z scores to test for shared sex-differentiated effects. Finally, we tested for sex differences in across-trait genetic correlations.ResultsWe observed no consistent sex differences in SNP-based heritability. Between-sex, within-trait genetic correlations were high, although

Manufacturing companies are always looking for ways to outperform their competitors. They are constantly trying to improve their efficiency and reduce costs. One method that improves efficiency and maximises the availability of production equipment is total productive maintenance (TPM), which is a lean optimisation philosophy tool that focuses on the optimisation of maintenance. Although TPM is known for improving maintenance, there are many obstacles to its successful implementation. Failure to properly implement TPM can result in additional costs and lost time, and it can have a negative impact on employees. For these reasons, a survey was prepared and conducted among several companies, each involved in a different field of work and having a different number of employees. The main findings of this research are the key factors that can negatively impact the implementation of TPM and lean tools in general, as well as suggestions for improvements that can ensure their successful implementation and sustainability. An analysis was conducted based on the size of each company as well as the job roles within them. The study covers issues that may arise during the implementation of TPM and other lean tools at all levels of the hierarchy in an enterprise and provides guidance on how to manage situations that may prevent the successful application of TPM.

Rare genetic variants can cause epilepsy, and genetic testing has been widely adopted for severe, paediatric-onset epilepsies. The phenotypic consequences of common genetic risk burden for epilepsies and their potential future clinical applications have not yet been determined. Using polygenic risk scores (PRS) from a European-ancestry genome-wide association study in generalized and focal epilepsy, we quantified common genetic burden in patients with generalized epilepsy (GE-PRS) or focal epilepsy (FE-PRS) from two independent non-Finnish European cohorts (Epi25 Consortium, n = 5705; Cleveland Clinic Epilepsy Center, n = 620; both compared to 20 435 controls). One Finnish-ancestry population isolate (Finnish-ancestry Epi25, n = 449; compared to 1559 controls), two European-ancestry biobanks (UK Biobank, n = 383 656; Vanderbilt biorepository, n = 49 494), and one Japanese-ancestry biobank (BioBank Japan, n = 168 680) were used for additional replications. Across 8386 patients with epilepsy and 622 212 population controls, we found and replicated significantly higher GE-PRS in patients with generalized epilepsy of European-ancestry compared to patients with focal epilepsy (Epi25: P = 1.64×10-15; Cleveland: P = 2.85×10-4; Finnish-ancestry Epi25: P = 1.80×10-4) or population controls (Epi25: P = 2.35×10-70; Cleveland: P = 1.43×10-7; Finnish-ancestry Epi25: P = 3.11×10-4; UK Biobank and Vanderbilt biorepository meta-analysis: P = 7.99×10-4). FE-PRS were significantly higher in patients with focal epilepsy compared to controls in the non-Finnish, non-biobank cohorts (Epi25: P = 5.74×10-19; Cleveland: P = 1.69×10-6). European ancestry-derived PRS did not predict generalized epilepsy or focal epilepsy in Japanese-ancestry individuals. Finally, we observed a significant 4.6-fold and a 4.5-fold enrichment of patients with generalized epilepsy compared to controls in the top 0.5% highest GE-PRS of the two non-Finnish European cohorts (Epi25: P = 2.60×10-15; Cleveland: P = 1.39×10-2). We conclude that common variant risk associated with epilepsy is significantly enriched in multiple cohorts of patients with epilepsy compared to controls-in particular for generalized epilepsy. As sample sizes and PRS accuracy continue to increase with further common variant discovery, PRS could complement established clinical biomarkers and augment genetic testing for patient classification, comorbidity research, and potentially targeted treatment.

A review of the current state of the theory and practice of bioenergy production from waste allowed us to identify the scientific and applied problem of substantiating the rational configuration of a modular anaerobic bioenergy system, taking into account the volume of organic waste generated in settlements. To solve this problem, this paper develops an approach and an algorithm for matching the configuration of a modular anaerobic bioenergy production system with the amount of organic waste generated in residential areas. Unlike the existing tools, this takes into account the peculiarities of residential areas, which is the basis for accurate forecasting of organic waste generation and, accordingly, determining the configuration of the bioenergy production system. In addition, for each of the scenarios, the anaerobic digestion process is modeled, which allows us to determine the functional indicators that underlie the determination of a rational configuration in terms of cost and environmental performance. Based on the use of the developed tools for the production conditions of the Golosko residential area, Lviv (Ukraine), possible scenarios for the installation of modular anaerobic bioenergy production systems are substantiated. It was found that the greatest annual benefits are obtained from the processing of mixed food and yard waste. The payback period of investments in modular anaerobic bioenergy production systems for given conditions of a residential area largely depends on their configuration and ranges from 3.3 to 8.4 years, which differ from each other by 2.5 times. This indicates that the developed toolkit is of practical value, as it allows the coordination of the rational configuration of modular anaerobic bioenergy production systems with real production conditions. In the future, it is recommended to use the proposed decision support system to model the use of biomass as an energy resource in residential areas, which ensures the determination of the rational configuration of a modular anaerobic bioenergy production system for given conditions. [ABSTRACT FROM AUTHOR]

The aim of the research is: to investigate the level of the development of creative potential of students – future foreign language teachers, to apply the program of group activity developed by us in order to develop the creativity of respondents, to analyze its effectiveness. The following theoretical methods of the research were used to solve the tasks formulated in the article: a categorical method, structural and functional methods, the methods of the analysis, systematization, modeling, generalization. Also we used experimental methods, such as statement research. For the last one we used such methodology, as: the test «Circles» by E.P. Thorens; the author’s methodology «The development of Creativity of teenagers» (Михальчук, Eр. Івашкевич & Яцюрик, 2021). The results of the research. In our research low results were obtained at both heuristic and reconstructive research levels. This indicates considerable difficulties that are arisen in a case when students are characterized with: a) the emergence of the ideas of solving the problem; b) making the design of the personal development; c) the embodiment of the idea in the activity, in communication with other students within the micro-group; d) the analysis and the evaluation of the results of pupils’ own creativity or innovation. The results having been obtained by us also indicate the need to organize special training for adolescents in order to make targeted influences on the development of their creativity. In such a way we’ve to make some conclusions. The concept of «creativity» is more general, because it includes creative qualities. Creativity reflects, in addition to subjective moments, also the process of reconciling novelty, innovation of the activity generated by the subject with the existing (so-called stereotypical) socio-cultural context. We consider creativity as the process of interaction that necessarily leads to the personal development. We also define creativity as an activity that creates something new, original, which is included not only into the history of the creator, but also into the history of science, art, etc. A similar point of view is expressed by us when we define creativity as going beyond the existing human knowledge, overcoming certain boundaries and obstacles. In such a way creativity means the creation of something new, which can mean both the transformation of the consciousness and behavior of the subject, generated by the person, but also which is alienated from his/her products. Conclusions. According to received data of our empirical research we offer some more definitions of the creativity, focusing the reader’s attention on the procedural aspect of this activity. In particular, we define creativity as the creation of something new in a situation where the problem-stimulus causes the invention of the so-called dominant, around which there are concentrated the necessary subjective statistics to solve this problem, requiring mandatory reference to their past, the person’s experience. The problem of creativity is considered by us through the concept of intellectual activity. The last is the phenomenon of self-movement of the activity, which is manifested in the process of cognitive activity of the individual, which goes beyond the requirements of this particular problem situation. In this process in the content of the ability to continue cognition independently outside there are actual the requirements of the initial situation, which situationally are not stimulated by productive activity and the secret of external forms of creativity is hidden. We mean the ability to see in the subject something new what other people do not see. Thus, the creative process is a kind of «derivative» of the intellect, refracted through the motivational sphere of the individual, which inhibits or stimulates its manifestations. After all, intelligence is determined by the dialectical relationships between two constructs. Defining, thus, the nature of creativity dwells on its immanent phenomenon, which considers creative abilities of the individual. We believe that understanding of human creative abilities should be considered as a kind of projection of unresolved problem of the nature of creativity. Although, in our opinion, having been given the existence of a variety of approaches of solving this problem, there are two main (or fundamental) ones: the approach to study creative abilities given the individual psychological differences of the subjects (B.М. Тeplov) and the approach of L.S. Vygotskyi (studying of creative abilities taking into account the personal qualities of a man). Defining the nature of creativity, we proceed from the delineation of the essence of the creative process, and from the characteristics of the creative product itself. This review coincides with our vision of this problem, because with this approach it is possible to consider the phenomenon of creativity not so much given the constant with genetic neurophysiological characteristics of homo, the creator, but taking into account the psychological manifestations of the individual’s ability to self-actualization (such as to the process of the man’s cognitive activity). We focus our attention on the position of the development of gifted and talented children. We believe that the learning and the development of such children creates an ideal model of creative human development, and the problem of the development of creativity should be considered in the paradigm of activity mediated by the creative abilities of the subject.

Introduction: Colorectal cancer is the third most common cancer type worldwide. Fluoropyrimidines and their prodrug-based regimens are widely applied as primary medications. The main enzyme responsible for the rate-limiting step in pyrimidine and for the 5-fluorouracil catabolism is dihydropyrimidine dehydrogenase (DPD).Aim: We aimed to screen DPD level and the changes of plasma antioxidant capacity of colorectal cancer patients on 5-fluorouracil regimen. Materials and methods: Human DPD Elisa Kit based on sandwich enzyme-linked immune-sorbent assay and spectrophotometric methods (FRAP and ABTS) were used in the study.Results: No statistically significant changes in plasma scavenging activity according to the results obtained in the ABTS system have been observed after evaluating all patients and considering DPD concentration. A decrease of the ferric reducing ability of patients’ plasma taken after the administered treatment was found. The increase of DPD level is accompanied by a decrease in the p values and therefore the statistical significance of the differences increases.Conclusions: Based on the aforementioned observations, it could be concluded that some aspects of plasma antioxidant capacity and individuals’ antioxidant status might be involved in the pathogenesis of the disease and could be altered by the activity of some enzymes. The cancer therapy in question, by the specificity of its mechanism of action, can modify patient’s oxidative status.

Objectives SPECTRUM is a unique multi-disciplinary, cross-sector collaborative research partnership between academics, government, and community organizations in Manitoba working together to address complex social problems. In our first research project, partners identified the need for quantitative evidence around outcomes of children involved with Child Protection Services (CPS), using linked administrative data. Approach From the SPECTRUM partnership, a research team with CPS expertise was established, including government policy-makers, community organizations representing First Nations families, and academics from multiple disciplines. The research is guided by an Advisory Circle of First Nations Knowledge Keepers. Linking health, education, CPS, and justice data we developed a matched cohort identifying children involved with CPS (2007-2018) for whom there was discretion in the decision to 1) place them in out-of-home care (n=19,718), or 2) keep them in their family home while providing services (n=28,154). Instrumental Variable analysis, with CPS agency as the instrument, will be used to compare outcomes. Results Following the trajectories of these two groups of CPS-involved children over time, we will compare their mental and physical health, educational achievement, and justice system involvement while accounting for individual-level (e.g., age, sex, chronic health conditions) and family-level (e.g., family income, maternal mental health, number of siblings) factors that may contribute to these outcomes. Preliminary findings will be workshopped with the SPECTRUM partnership to facilitate discussions on framing the evidence for policy makers. The SPECTRUM policy team will then prepare policy recommendations for government to consider. The Advisory Circle and a youth advisory squad will facilitate contextualizing and mobilizing findings. Actions taken by government in response to material provided will be monitored and will inform the development of subsequent research projects conducted by SPECTRUM. Conclusion Government and community stakeholder involvement throughout bolsters the likelihood of evidence translating into program and policy changes. This is not a situation where academics are telling government how to do their jobs – this is government, community organizations, and academics working together with the shared goal of better outcomes for children.

Vintage postporn es un podcast colectivo (de Rachele Borghi, Slavina y Emilie Viney) que hace transitar las palabras, las aproximaciones, las temáticas y las voces de la postpornografía tal como se desarrolló en España e Italia entre 2000 y 2015. Si “mi sexualidad es una creación artística” según afirma Lucía Egaña Rojas en su documental epónimo, “Vintage postporn” se enfoca en el cuerpo como laboratorio de experimentación y placer y también como herramienta de resistencia. Con citas de Emma Goldman y Diana Pornoterrorista Rachele Borghi es pornactivista transfeminista, profesora titular de geografía en la Universidad de la Sorbona. Estudia las transgresiones performáticas en el espacio público como reacción en contra de las normas impuestas así como el cuerpo entendido como laboratorio y herramienta de resistencia. Sus líneas de investigación son la visibilización de las normas en los espacios públicos e institucionales (especialmente la academia), las prácticas que permiten romperlas y los espacios de contagio entre ámbitos académicos, artísticos y militantes. Sus contactos con colectivos postporno y queer le han permitido cuestionar su propia práctica, su posicionamiento en la academia y han resaltado la urgencia de encontrar y experimentar nuevos acercamientos para no reproducir el binomio teoría-producción teórica / practica-producción militante. Décolonialité et privilège. Devenir complices (2021, ed. Daronnes) es su último ensayo. slavina es performer, escritora y educadora transfeminista: define porno-activismo su ámbito de investigación y creación. vive y trabaja entre Italia y el estado español. su producción está enfocada en las políticas del cuerpo y de los cuidados y se desarrolla a través de la realización de experiencias de empoderamiento erotico comunitario. en sus proyectos (video, cabaret, talleres) trabaja el potencial político de las intimidades compartidas. en 2012 ha publicado un libro de relatos eróticos en italiano, pero su orgullo es sobretodo lo de haber facilitado feministement las conexiones entre su tierra de origen y el contexto transfeminista español, traduciendo y promoviendo autorxs y obras. es co-fundadora del colectivo psicoerótica femminista, una experimentación terapéutica creativa y colectiva que integra pornografía y psicoanálisis. en sus ratos libres es madre y practica yoga. Emilie Viney es catedrática de geografía de la enseñanza segundaria y docente en la Universidad de la Sorbona. Enseña entre otras cosas geografía de la dominación, geografía de los sexos y sexualidad, epistemología de la geografía. Se interesa por la manera de transmitir los saberes en geografía sin reproducir las relaciones de poder mediante pedagogías críticas. Se involucra con gusto en los proyectos en los que Rachele Borghi le invita a participar.

Russian-Japanese relations are historically ambiguous. Recently, the situation began to change and the Cross Year of Japan in Russia and Russia in Japan project (2018-2019) influenced these changes. The article is an overview of the materials of the Russian and Japanese media on the activities of this international project.

Background. We previously found that a decrease in the number of NKT cells and activated CD 25+ peripheral blood lymphocytes (PBLs) before neoadjuvant chemotherapy was associated with an increased likelihood of disease progression in patients with locally advanced triple-negative breast cancer (TN BC).The purpose of this study was to determine the relationship between the initial number of NKT-and CD 25+ PBLs and relapsefree survival (RFS)/overall survival (OS ) in patients with TN BC who received neoadjuvant chemotherapy with cisplatin and paclitaxel followed by surgery.Material and Methods. The study included patients with stage II and III TN BC. The follow-up time was 36 and 66.9 months. Immediately before chemotherapy, the percentage of CD 3+CD 16+CD 56+ (NKT) -, CD 25+- and CD 8+ PBLs was determined by flow cytometry. Statistical analysis of the data was carried out using the Statistics 7 software package. The Kaplan-Meier method was used to determine the relationship between immunological parameters and RFS/ OS .Results. The decreased level of NKT cells before treatment was associated with a decrease in the 3-year RFS [Me: 20.1 (0.533 and 39.7) months] compared to that observed in patients with higher percentage of these cells than in the control (Me was not achieved). There were no statistically significant differences in the 3-year OS between the groups. The initially reduced number of CD 25+ lymphocytes in comparison with the control was associated with decreased rates of both RFS and OS . The difference in DFS and OS was more significant between the groups of patients who simultaneously had an increased initial number of both NKT and CD 25+ cells and patients in whom both cell populations were below normal levels.Conclusion. The initial (prior to chemotherapy) number of NKT and activated CD 25+ PBLs can apparently be a predictive factor in TN BC patients, who received neoadjuvant chemotherapy with cisplatin and paclitaxel.