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The article reveals the objective prerequisites for the change of legislation. These are not clarifications and amendments, but reforms that are reflected in significant changes in civil, labor, family, inheritance, and procedural legislation. This is usually associated with the cancellation of the old and the adoption of a new codified Act, but in modern Russia, it is associated with the modification and cancellation of a large number of statutory acts. The article illustrates the stability of industry legislation in Australia, Austria, Germany and the USA. The theory of generations, generally accepted in developed countries, is analyzed from the point of view of the need to change legislation. Historical analysis shows that in the observable past, the problem of generational change, regardless of demographic wave, predetermined the need for reforms in Russia in the middle of the 19th century. This is extensively reflected in the Russian literature of the second half of the 19th century. The article shows the differences between demographic waves, generations and waves that determine the need for a change in legislation. It is postulated that the wave that determines the change of legislation should be considered as a social wave. The need for a significant change in legislation is closely connected with social waves. The author criticizes the state of constant legislation updating without the need caused by such a social wave. The author concludes about the negative consequences of unreasonably frequent changes in legislation.

The article describes the geographical direction in sociology and topicality of modern geosocial investigations. It analyses the concepts «geopolitics» and «geosociology», substantiates the need of identifying geosocial types in modern society. It reveals that the majority of the states in the world are built on the basis of a single geosocial type, while the Russian Federation includes in its borders and its structure several geosocial types, such as: the settled, the settled-forest, the mountainous, the nomadic, the marine, as well as mixed types. It specifies the settled-forest geosocial type to be traditionally dominating in the majority of the Russian regions. It proves that the administrative division of the Russian Federation subjects is often a little artificial, as the same geosocial type, including the ethnos, lives on the territory of different regions and even Federal Districts. The typology obtained will allow further to investigate regularities of ethnos development depending on the geographical environment.

SummaryAs a Mendelian neurodegenerative disorder, the genetic risk of Huntington’s disease (HD) is conferred entirely by an HTT CAG repeat expansion whose length is the primary determinant of the rate of pathogenesis leading to disease onset. To investigate the pathogenic process that precedes disease, we used genome-wide association (GWA) analysis to identify loci harboring genetic variations that alter the age at neurological onset of HD. A chromosome 15 locus displays two independent effects that accelerate or delay onset by 6.1 years and 1.4 years, respectively, whereas a chromosome 8 locus hastens onset by 1.6 years. Association at MLH1 and pathway analysis of the full GWA results support a role for DNA handling and repair mechanisms in altering the course of HD. Our findings demonstrate that HD disease modification in humans occurs in nature and offer a genetic route to identifying in-human validated therapeutic targets in this and other Mendelian disorders.PaperClip

© 2015, Elsevier Inc. All rights reserved. Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 × 10-12 after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 × 10-11), cholesterol transport (P = 2.96 × 10-9), and proteasome-ubiquitin activity (P = 1.34 × 10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P =.002-.05). Conclusions: The immune response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics., Medical Research Council, Alzheimer’s Research UK, and theWelsh Assembly Government. ADGC and CHARGE were supported by the National Institutes of Health, National Institute on Aging (NIH-NIA). CHARGE was also supported by Erasmus Medical Center and Erasmus University. IGAP was funded by the French National Foundation on Alzheimer’s Disease and Related Disorders, the Centre National de Genotypage and the Institut Pasteur de Lille, Inserm, FRC (Fondation pour la Recherche sur le Cerveau), and Rotary. This work has been developed and supported by the LABEX (Laboratory of Excellence Program Investment for the Future) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer’s disease).

Neuroticism is a personality trait of fundamental importance for psychological well-being and public health. It is strongly associated with major depressive disorder (MDD) and several other psychiatric conditions. Although neuroticism is heritable, attempts to identify the alleles involved in previous studies have been limited by relatively small sample sizes. Here we report a combined meta-analysis of genome-wide association study (GWAS) of neuroticism that includes 91 370 participants from the UK Biobank cohort, 6659 participants from the Generation Scotland: Scottish Family Health Study (GS:SFHS) and 8687 participants from a QIMR (Queensland Institute of Medical Research) Berghofer Medical Research Institute (QIMR) cohort. All participants were assessed using the same neuroticism instrument, the Eysenck Personality Questionnaire-Revised (EPQ-R-S) Short Form’s Neuroticism scale. We found a single-nucleotide polymorphism-based heritability estimate for neuroticism of ∼15% (s.e.=0.7%). Meta-analysis identified nine novel loci associated with neuroticism. The strongest evidence for association was at a locus on chromosome 8 (P=1.5 × 10−15) spanning 4 Mb and containing at least 36 genes. Other associated loci included interesting candidate genes on chromosome 1 (GRIK3 (glutamate receptor ionotropic kainate 3)), chromosome 4 (KLHL2 (Kelch-like protein 2)), chromosome 17 (CRHR1 (corticotropin-releasing hormone receptor 1) and MAPT (microtubule-associated protein Tau)) and on chromosome 18 (CELF4 (CUGBP elav-like family member 4)). We found no evidence for genetic differences in the common allelic architecture of neuroticism by sex. By comparing our findings with those of the Psychiatric Genetics Consortia, we identified a strong genetic correlation between neuroticism and MDD and a less strong but significant genetic correlation with schizophrenia, although not with bipolar disorder. Polygenic risk scores derived from the primary UK Biobank sample captured ∼1% of the variance in neuroticism in the GS:SFHS and QIMR samples, although most of the genome-wide significant alleles identified within a UK Biobank-only GWAS of neuroticism were not independently replicated within these cohorts. The identification of nine novel neuroticism-associated loci will drive forward future work on the neurobiology of neuroticism and related phenotypes.

Correction to: Molecular Psychiatry 21, 749–757; doi:10.1038/mp.2016.49 The GWAS of neuroticism conducted within the Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute cohort did not include covariates of age, sex, genotyping batch and 10 principal components. Adding these covariates does not substantially change the pattern of results within the meta-analysis, but P-values for the nine reported loci have changed slightly (please see revised Figure 2, Table 2A and Table 2B).

Aim. To evaluate late nephrotoxicity of intensive modified program NHL-BFM-90 (mNHL-BFM-90) in adult poor-prognosis patients with diffuse large B-cell lymphoma (DLBCL). Materials and methods. The data of laboratory tests of blood and urine of 40 patients with DLBCL which received mNHL-BFM-90 protocol in the Hematology Research Center in the period from 2002 to 2009 years was analyzed. Group consisted of 20 men, 20 women, aged from 31 to 76 years, median age - 56.5 years at the time of the survey, the median period after therapy- 6 years. Individual cumulative dose of ifosfamide - 8-12 g / m 2 , cyclophosphamide - 2-3 g / m 2 , methotrexate - 6-9 g / m 2 . Comparison group included 19 patients (8 men and 11 women), aged from 39 to 78 years, median age - 70 years at the time of the survey, who received therapy to CHOP or R-CHOP. The median period after therapy - 5,5 years. Individual cumulative dose of cyclophosphamide - 3-6 g / m 2 . Laboratory tests of blood and urine were performed before chemotherapy and after 5 years after treatment. Results. From all 40 patients with DLBCL received mNHL-BFM-90, signs of chronic kidney disease were found in 32 (80%) patients, only 2 (5%) of them showed a decrease in creatinine clearance daily. In comparison group signs of chronic kidney disease were found in 12 (63%) patients, 2 patients (10.5%) showed a reduction in the daily creatinine clearance. No significant differences in the manifestations of nephrotoxicity in the long term between comparison groups were found. No significant differences in the manifestations of nephrotoxicity in the long term period were found between two groups of patients (who underwent and not underwent acute renal failure during high-dose chemotherapy). Amount of nephrotoxicity signs was significantly dependent on the presence of hypertensive disease in history (p = 0.02). Conclusion. Nephrotoxicity of high-dose mNHL-BFM 90 exceeds significantly nephrotoxicity program CHOP / R-CHOP. Conducting high-dose chemotherapy in 10 (25%) patients complicated by acute renal failure, 2 (20%) patients required hemodialysis in contrast to the group of standard chemotherapy without such complications (p=0,01). However, in the long term observations there weren9t significant differences in the nephrotoxic manifestations between two groups. Impaired renal function in the long term period observed in 100% of patients undergoing acute renal failure during treatment and only in 71% of patients without acute renal failure (p=0,04). It was comparable repairing of renal function in the long term in patients undergoing high-dose therapy between patients with and without acute renal failure among those who showed signs of chronic kidney disease. Disclosures No relevant conflicts of interest to declare.