Новации в статистике трудовых отношений (по материалам 20-й Международной конференции статистиков труда)

On the basis of the proceedings of the 20th International Conference of Labour Statisticians the authors, who had attended the conference as part of the Russian delegation, reviewed key novations that were proposed and discussed under the auspices of the International Labour Organization. The article covers the adopted resolutions and recommendations that aim to ensure international comparability of indicators of the Sustainable Development Goals (SDGs). The SDGs enable decent work and promote methodological consistency across countries when it comes to specific topics of labour statistics such as work relationships, child labour and a number of other priority areas.The focal point of the article is the analysis of key provisions and concepts adopted at the conference, in particular, the Resolution concerning statistics on work relationships. It defines the operational concepts, classifications and information sources for compiling statistical surveys of workers in a fundamentally new aspect - characteristics of the work relationship. The article covers statistical classification that can serve as a basis when identifying and classifying workers by characteristics of the work relationship following the cross-cutting variables and categories: the type of authority and the type of economic risk. The paper provides insights into the scheme of the interrelation of statistics on work relationships, listed in the Resolution, that had been developed by the authors.The authors formulated recommendations on directions for onward development of labour statistics with regard to international standards. На основе материалов 20-й Международной конференции статистиков труда (МКСТ) авторами статьи - участниками этой конференции в составе российской делегации - проанализированы основные новации, которые в виде предложений обсуждались под эгидой Международной организации труда. Прокомментированы принятые на данной конференции резолюции и рекомендации, обеспечивающие международную сопоставимость показателей достижения Целей устойчивого развития по обеспечению достойного труда, а также определяющие методологическое единство стран в области статистики трудовых отношений, детского труда и ряда других актуальных направлений. Центральное место в статье отведено анализу ключевых положений и концепций, принятых на указанной конференции, в частности Резолюции о статистике трудовых отношений (РСТО), определяющей базовые понятия, классификации и информационные источники для организации и проведения статистических наблюдений работников в принципиально новом аспекте - по характеристикам трудовых отношений, в которых находится работник в связи с выполняемой им работой. Прокомментированы новые статистические классификации, на основе которых можно идентифицировать и распределить работников по признакам трудовых отношений, основанные на перекрестной группировке по типам полномочий и типам экономических рисков. Охарактеризованы разработанные авторами схемы взаимосвязи категорий статистики трудовых отношений, указанных в Резолюции.Сформулированы рекомендации по дальнейшим направлениям развития статистики труда с учетом требований международных стандартов

Mitochondrial DNA Variant Discovery and Evaluation in Human Cardiomyopathies through Next-Generation Sequencing

Mutations in mitochondrial DNA (mtDNA) may cause maternally-inherited cardiomyopathy and heart failure. In homoplasmy all mtDNA copies contain the mutation. In heteroplasmy there is a mixture of normal and mutant copies of mtDNA. The clinical phenotype of an affected individual depends on the type of genetic defect and the ratios of mutant and normal mtDNA in affected tissues. We aimed at determining the sensitivity of next-generation sequencing compared to Sanger sequencing for mutation detection in patients with mitochondrial cardiomyopathy. We studied 18 patients with mitochondrial cardiomyopathy and two with suspected mitochondrial disease. We “shotgun” sequenced PCR-amplified mtDNA and multiplexed using a single run on Roche's 454 Genome Sequencer. By mapping to the reference sequence, we obtained 1,300× average coverage per case and identified high-confidence variants. By comparing these to >400 mtDNA substitution variants detected by Sanger, we found 98% concordance in variant detection. Simulation studies showed that >95% of the homoplasmic variants were detected at a minimum sequence coverage of 20× while heteroplasmic variants required >200× coverage. Several Sanger “misses” were detected by 454 sequencing. These included the novel heteroplasmic 7501T>C in tRNA serine 1 in a patient with sudden cardiac death. These results support a potential role of next-generation sequencing in the discovery of novel mtDNA variants with heteroplasmy below the level reliably detected with Sanger sequencing. We hope that this will assist in the identification of mtDNA mutations and key genetic determinants for cardiomyopathy and mitochondrial disease

MtSNPscore: a combined evidence approach for assessing cumulative impact of mitochondrial variations in disease

Human mitochondrial DNA (mtDNA) variations have been implicated in a broad spectrum of diseases. With over 3000 mtDNA variations reported across databases, establishing pathogenicity of variations in mtDNA is a major challenge. We have designed and developed a comprehensive weighted scoring system (MtSNPscore) for identification of mtDNA variations that can impact pathogenicity and would likely be associated with disease. The criteria for pathogenicity include information available in the literature, predictions made by various in silico tools and frequency of variation in normal and patient datasets. The scoring scheme also assigns scores to patients and normal individuals to estimate the cumulative impact of variations. The method has been implemented in an automated pipeline and has been tested on Indian ataxia dataset (92 individuals), sequenced in this study, and other publicly available mtSNP dataset comprising of 576 mitochondrial genomes of Japanese individuals from six different groups, namely, patients with Parkinson's disease, patients with Alzheimer's disease, young obese males, young non-obese males, and type-2 diabetes patients with or without severe vascular involvement. MtSNPscore, for analysis can extract information from variation data or from mitochondrial DNA sequences. It has a web-interface http://bioinformatics.ccmb.res.in/cgi-bin/snpscore/Mtsnpscore.pl webcite that provides flexibility to update/modify the parameters for estimating pathogenicity

Genome Digging: Insight into the Mitochondrial Genome of Homo

A fraction of the Neanderthal mitochondrial genome sequence has a similarity with a 5,839-bp nuclear DNA sequence of mitochondrial origin (numt) on the human chromosome 1. This fact has never been interpreted. Although this phenomenon may be attributed to contamination and mosaic assembly of Neanderthal mtDNA from short sequencing reads, we explain the mysterious similarity by integration of this numt (mtAncestor-1) into the nuclear genome of the common ancestor of Neanderthals and modern humans not long before their reproductive split.Exploiting bioinformatics, we uncovered an additional numt (mtAncestor-2) with a high similarity to the Neanderthal mtDNA and indicated that both numts represent almost identical replicas of the mtDNA sequences ancestral to the mitochondrial genomes of Neanderthals and modern humans. In the proteins, encoded by mtDNA, the majority of amino acids distinguishing chimpanzees from humans and Neanderthals were acquired by the ancestral hominins. The overall rate of nonsynonymous evolution in Neanderthal mitochondrial protein-coding genes is not higher than in other lineages. The model incorporating the ancestral hominin mtDNA sequences estimates the average divergence age of the mtDNAs of Neanderthals and modern humans to be 450,000-485,000 years. The mtAncestor-1 and mtAncestor-2 sequences were incorporated into the nuclear genome approximately 620,000 years and 2,885,000 years ago, respectively.This study provides the first insight into the evolution of the mitochondrial DNA in hominins ancestral to Neanderthals and humans. We hypothesize that mtAncestor-1 and mtAncestor-2 are likely to be molecular fossils of the mtDNAs of Homo heidelbergensis and a stem Homo lineage. The d(N)/d(S) dynamics suggests that the effective population size of extinct hominins was low. However, the hominin lineage ancestral to humans, Neanderthals and H. heidelbergensis, had a larger effective population size and possessed genetic diversity comparable with those of chimpanzee and gorilla

Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial

Background. Pediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM. Methods. TBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL). Results. Of 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P < .01). Conclusions. In a pediatric TBM trial, functional outcomes were excellent overall. The trend toward higher frequency of adverse events but better neurocognitive outcomes in children receiving high-dose rifampicin requires confirmation in a larger trial. Clinical Trials Registration. NCT02958709

Aggression, anxiety and vocalizations in animals: GABA A and 5-HT anxiolytics

A continuing challenge for preclinical research on anxiolytic drugs is to capture the affective dimension that characterizes anxiety and aggression, either in their adaptive forms or when they become of clinical concern. Experimental protocols for the preclinical study of anxiolytic drugs typically involve the suppression of conditioned or unconditioned social and exploratory behavior (e.g., punished drinking or social interactions) and demonstrate the reversal of this behavioral suppression by drugs acting on the benzodiazepine-GABA A complex. Less frequently, aversive events engender increases in conditioned or unconditioned behavior that are reversed by anxiolytic drugs (e.g., fear-potentiated startle). More recently, putative anxiolytics which target 5-HT receptor subtypes produced effects in these traditional protocols that often are not systematic and robust. We propose ethological studies of vocal expressions in rodents and primates during social confrontations, separation from social companions, or exposure to aversive environmental events as promising sources of information on the affective features of behavior. This approach focusses on vocal and other display behavior with clear functional validity and homology. Drugs with anxiolytic effects that act on the benzodiazepine-GABA A receptor complex and on 5-HT 1A receptors systematically and potently alter specific vocalizations in rodents and primates in a pharmacologically reversible manner; the specificity of these effects on vocalizations is evident due to the effectiveness of low doses that do not compromise other physiological and behavioral processes. Antagonists at the benzodiazepine receptor reverse the effects of full agonists on vocalizations, particularly when these occur in threatening, startling and distressing contexts. With the development of antagonists at 5-HT receptor subtypes, it can be anticipated that similar receptor-specificity can be established for the effects of 5-HT anxiolytics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46351/1/213_2005_Article_BF02245590.pd

Determination of N-acetylation phenotyping in a Greek population using caffeine as a metabolic probe

Studies of isoniazid, the well known antituberculosis drug, have revealed that N-acetylation polymorphism, is of great clinical importance. In humans, N-acetylation is one of the most important pathways in the inactivation of isoniazid. Caffeine, which is also biotransformed by N-acetylation, has been widely used as an in vivo probe for the assessment of N-acetyltransferase polymorphism. The activity of N-acctyltransferase can be estimated from the urinary metabolic ratio of two caffeine metabolites, namely, 5-acetylamino-6-formy-lamino-3-methyluracil (AFMU), and 1-methylxanthine (1X) after the ingestion of caffeine. In the present study caffeine was used as a metabolic probe to determine N-acetyltransferase polymorpism in 83 healthy Creek volunteers by means of the molar ratio of AFMU and 1X determined in urine following ingestion of 200 mg caffeine. Frequency distribution analysis of the metabolic ratios AFMU/1X revealed two distinct groups with 66.3% (n = 55) slow acetylators and 33.7 % (n = 28) rapid acetylators. No statistically significant difference was detected between slow and fast acetylators in terms of gender, smoking habits and caffeine-intake habits. These results are in agreement with previous studies on N-acetyltransferase activity in Caucasians using caffeine as a metabolic probe. They also agree with reports on N-acetyltransferase activity in Greek tuberculosis patients using isoniazid as a metabolic probe. Thus, the use of caffeine as a metabolic probe is a reliable method for the assessment of N-acetyltransferase activity in the Greek population