Сутність та особливості періодизації функціонування прокуратури України

У статті розглядаються суть та особливості періодизації функціонування прокуратури України як одного з основних методологічних аспектів наукового дослідження. Крім того, проведений аналіз різних підходів до періодизації функціонування прокуратури, як вітчизняних, так і деяких зарубіжних науковців. Ключові слова: прокуратура, періодизація розвитку прокуратури.В статье рассматриваются сущность и особенности периодизации функционирования прокуратуры Украины как одного из основных методологических аспектов научного исследования. Кроме того, проведен анализ различных подходов к периодизации функционирования прокуратуры, как отечественных, так и некоторых зарубежных ученых. Ключевые слова: прокуратура, периодизация развития прокуратуры.This article discusses the nature and features periodization of functioning Prosecutor of Ukraine as one of the main methodological aspects of research. In addition, analysis of different approaches to periodization functioning prosecutor's office, both domestic, and some foreign scholars. Key words: prosecutor's office, periodization development of prosecutor's office

Bestrijding aardbeimijt in plantmateriaal: Eindrapport onderzoekfase III & IV

Op basis van een jaarlijkse ontheffing werd in Nederland voor de ontsmetting van aardbeiplanten voor vermeerdering tot in het jaar 2007 methylbromide toegepast. Door het gecontroleerd begassen van het basisplantgoed (moederplanten) met methylbromide werd o.a. de gevreesde aardbeimijt zeer effectief bestreden, tot minimaal 99,8%. Hiervoor werd in Nederland jaarlijks 120 kg actieve stof methylbromide ingezet. Vanwege de ongunstige neveneffecten van methylbromide, o.a. op aantasting van de ozonlaag, is internationaal afgesproken om het gebruik van deze stof te beeindigen. Wereldwijd wordt gezocht naar alternatieven voor de toepassing van methylbromide. Dit afsluitende projectrapport gaat in op het onderzoek naar enkele mogelijke alternatieven voor methylbromide en de precieze afstelling en opschalingnaar praktijkniveau van de meest perspectiefvolle methode, de CAwarmtebehandeling

Policy and practice review: a first guideline on the use of pharmacogenetics in clinical psychiatric practice

Effective pharmacologic treatments for psychiatric disorders are available, but their effect is limited due to patients' genetic heterogeneity and low compliance-related to frequent adverse events. Only one third of patients respond to treatment and experience remission. Pharmacogenetics is a relatively young field which focusses on genetic analyses in the context of the metabolism and outcome of drug treatment. These genetic factors can, among other things, lead to differences in the activity of enzymes that metabolize drugs. Recently, a clinical guideline was authorized by the Dutch Clinical Psychiatric Association (NVvP) on the clinical use of pharmacogenetics in psychiatry. The main goal was to provide guidance, based on current evidence, on how to best use genotyping in clinical psychiatric practice. A systematic literature search was performed, and available publications were assessed using the GRADE methodology. General recommendations for psychiatric clinical practice were provided, and specific recommendations per medication were made available. This clinical guideline for caregivers prescribing psychotropic drugs is the product of a broad collaboration of professionals from different disciplines, making use of the information available at the Dutch Pharmacogenetics Working Group (DPWG) and the Clinical Pharmacogenetics Implementation Consortium (CPIC) so far. We summarize the relevant literature and all recommendations in this article. General recommendations are provided and also detailed recommendations per medication. In summary we advise to consider genotyping, when there are side effects or inefficacy for CYP2C19 and CYP2D6. When genotype information is available use this to select the right drug in the right dose for the right patient.Public Health and primary carePrevention, Population and Disease management (PrePoD

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Skewed X-inactivation is common in the general female population

X-inactivation is a well-established dosage compensation mechanism ensuring that X-chromosomal genes are expressed at comparable levels in males and females. Skewed X-inactivation is often explained by negative selection of one of the alleles. We demonstrate that imbalanced expression of the paternal and maternal X-chromosomes is common in the general population and that the random nature of the X-inactivation mechanism can be sufficient to explain the imbalance. To this end, we analyzed blood-derived RNA and whole-genome sequencing data from 79 female children and their parents from the Genome of the Netherlands project. We calculated the median ratio of the paternal over total counts at all X-chromosomal heterozygous single-nucleotide variants with coverage ≥10. We identified two individuals where the same X-chromosome was inactivated in all cells. Imbalanced expression of the two X-chromosomes (ratios ≤0.35 or ≥0.65) was observed in nearly 50% of the population. The empirically observed skewing is explained by a theoretical model where X-inactivation takes place in an embryonic stage in which eight cells give rise to the hematopoietic compartment. Genes escaping X-inactivation are expressed from both alleles and therefore demonstrate less skewing than inactivated genes. Using this characteristic, we identified three novel escapee genes (SSR4, REPS2, and SEPT6), but did not find support for many previously reported escapee genes in blood. Our collective data suggest that skewed X-inactivation is common in the general population. This may contribute to manifestation of symptoms in carriers of recessive X-linked disorders. We recommend that X-inactivation results should not be used lightly in the interpretation of X-linked variants