Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Resolving the chemical structures of off-odorants and potentially harmful substances in toys - example of children's swords

Most children’s toys on the market are primarily made out of plastic and other complex composite materials. Consumer complaints about offensive odors or irritating effects associated with toy products have increased in recent years. One example is the strongly perceivable negative odor reported for a particular series of toy swords. Characterizing the presence of contaminants, including those that have the potential to be deleterious to health, in such products is a significant analytical challenge due to the high baseline abundance of chemical constituents of the materials used in the products. In the present study, the nature of offensive odorants associated with toy sword products was examined by gas chromatography (GC). After initial sensory evaluations, the volatile compounds from the toy products were recovered using solvent extraction and solvent-assisted flavor evaporation. The extracts were analyzed using GC-olfactometry (GC-O) and two-dimensional GC-O coupled with mass spectrometry (GC-GC-MS/O). A total of 26 odor-active compounds, including aromatic hydrocarbons and phenols, were identified among numerous non-odorous volatile by-products. These substances also included polycyclic aromatic hydrocarbons, which were analyzed by GC-MS. Representative substances were naphthalene and 1,2-dihydronaphthalene that exhibited moldy, mothball-like odor impressions, and phenol derivatives with leather-like, phenolic, horse-stable-like smells. The odorants detected correlated with the assigned attributes from the sensory analyses. This study clearly shows that the detection and identification of such odorous contaminants can provide key indications of potentially harmful yet unknown substances in everyday products such as toys

Characterization of off-odours and potentially harmful substances in a fancy dress accessory handbag for children

A fancy dress accessory handbag for children was claimed by consumers to exhibit an offensive smell. Sensory characterization by an expert panel revealed, amongst others, rubber- and car tire - like notes. For elucidation of the molecular reasons of this sensory defect, the volatile fraction of the product was isolated by means of solvent extraction and high vacuum distillation. Identification of the main odorants was accomplished by means of one- and two-dimensional gas chromatography, with parallel mass spectrometric and olfactometric detection. In total more than 60 odorants were detected in the sample and more than 30 of these odour-active substances could be identified. Amongst them were a number of naphthalene derivatives as well as saturated and mono- or di-unsaturated carbonyl compounds. The naphthalene derivatives that were identified in the children’s article appeared to be mainly responsible for the characteristic off-odour. Additionally, a GC-MS-screening for polycyclic aromatic hydrocarbons (PAHs) was performed, which revealed the presence of 15 PAHs in total. However, 14 of them were of no relevance for the smell of the product

Toy swords revisited: Identification of additional odour-active contaminants

Odorants related to offensive odours in three children’s toy swords were identified and characterized by human sensory and chemical analyses. Samples were initially evaluated by a trained sensory panel. Panellists reported unpleasant smells in all samples that were dominated by mothball-like, phenolic and rubber-like notes and additionally almond-like and fatty notes. The odorants from the samples were then extracted using dichloromethane and subsequent solvent-assisted flavour evaporation distillation. Enriched distillates were then analysed by means of single and two-dimensional gas chromatography–mass spectrometry/olfactometry. An additional screening analysis for polycyclic aromatic hydrocarbons was also performed on all samples. The most predominant odorants identified in the samples were naphthalene, 1- and 2-methylnaphthalene and diverse dimethylnaphthalene isomers with gasoline-like smells. Acetophenone, with an almond-like, flowery smell, was also detected. Furthermore, the phenolic/leather-like smelling substances 3-ethylphenol, 3-hydroxyacetophenone, and 3-methoxyacetophenone were identified in one sample

Correction to: Comparative effectiveness and safety of non-vitamin K antagonists for atrial fibrillation in clinical practice: GLORIA-AF Registry

International audienceIn this article, the name of the GLORIA-AF investigator Anastasios Kollias was given incorrectly as Athanasios Kollias in the Acknowledgements. The original article has been corrected

Patterns of oral anticoagulant use and outcomes in Asian patients with atrial fibrillation: a post-hoc analysis from the GLORIA-AF Registry

Background: Previous studies suggested potential ethnic differences in the management and outcomes of atrial fibrillation (AF). We aim to analyse oral anticoagulant (OAC) prescription, discontinuation, and risk of adverse outcomes in Asian patients with AF, using data from a global prospective cohort study. Methods: From the GLORIA-AF Registry Phase II-III (November 2011-December 2014 for Phase II, and January 2014-December 2016 for Phase III), we analysed patients according to their self-reported ethnicity (Asian vs. non-Asian), as well as according to Asian subgroups (Chinese, Japanese, Korean and other Asian). Logistic regression was used to analyse OAC prescription, while the risk of OAC discontinuation and adverse outcomes were analysed through Cox-regression model. Our primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACE). The original studies were registered with ClinicalTrials.gov, NCT01468701, NCT01671007, and NCT01937377. Findings: 34,421 patients were included (70.0 ± 10.5 years, 45.1% females, 6900 (20.0%) Asian: 3829 (55.5%) Chinese, 814 (11.8%) Japanese, 1964 (28.5%) Korean and 293 (4.2%) other Asian). Most of the Asian patients were recruited in Asia (n = 6701, 97.1%), while non-Asian patients were mainly recruited in Europe (n = 15,449, 56.1%) and North America (n = 8378, 30.4%). Compared to non-Asian individuals, prescription of OAC and non-vitamin K antagonist oral anticoagulant (NOAC) was lower in Asian patients (Odds Ratio [OR] and 95% Confidence Intervals (CI): 0.23 [0.22-0.25] and 0.66 [0.61-0.71], respectively), but higher in the Japanese subgroup. Asian ethnicity was also associated with higher risk of OAC discontinuation (Hazard Ratio [HR] and [95% CI]: 1.79 [1.67-1.92]), and lower risk of the primary composite outcome (HR [95% CI]: 0.86 [0.76-0.96]). Among the exploratory secondary outcomes, Asian ethnicity was associated with higher risks of thromboembolism and intracranial haemorrhage, and lower risk of major bleeding. Interpretation: Our results showed that Asian patients with AF showed suboptimal thromboembolic risk management and a specific risk profile of adverse outcomes; these differences may also reflect differences in country-specific factors. Ensuring integrated and appropriate treatment of these patients is crucial to improve their prognosis. Funding: The GLORIA-AF Registry was funded by Boehringer Ingelheim GmbH