Comparative Responses in Lung Function Measurements with Tiotropium in Adolescents and Adults, and Across Asthma Severities:A Post Hoc Analysis

INTRODUCTION: Airway obstruction is usually assessed by measuring forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and peak expiratory flow (PEF). This post hoc study investigated comparative responses of lung function measurements in adults and adolescents (full analysis set, N = 3873) following treatment with tiotropium Respimat®. METHODS: Lung function outcomes were analysed from five phase III trials in adults (≥ 18 years) with symptomatic severe, moderate and mild asthma (PrimoTinA-asthma®, MezzoTinA-asthma® and GraziaTinA-asthma®, respectively), and one phase III trial in adolescents (12-17 years) with symptomatic moderate asthma (RubaTinA-asthma®). Changes from baseline versus placebo in FEV1, FVC, PEF and FEV1/FVC ratio with tiotropium 5 µg or 2.5 µg added to at least stable inhaled corticosteroids at week 24 (week 12 in GraziaTinA-asthma) were analysed. RESULTS: All lung function measures improved in all studies with tiotropium 5 µg (mean change from baseline versus placebo), including peak FEV1 (110-185 mL), peak FVC (57-95 mL) and morning PEF (15.8-25.6 L/min). Changes in adolescents were smaller than those in adults, and were statistically significant primarily for FEV1 and PEF, but not for FVC. CONCLUSION: Consistent improvements were seen across all lung function measures with the addition of tiotropium to other asthma treatments in adults across all severities, whereas the improvements with tiotropium in adolescents primarily impacted measures of flow rather than lung volume. This may reflect less pronounced airway remodelling and air trapping in adolescents with asthma versus adults

Особенности формирования структуры ЗТВ и зон оплавления покрытия на основе стали 10Р6М5 электронным лучом в вакууме

Особенности формирования структуры в зоне оплавления и зоне термического влияния композиционного покрытия на основе стали 10Р6М5 в ходе вакуумного импульсного электронного воздействияEigenschaften der Strukturbildung in der Schmelzzone und die Warmeeinflu?zone, auf der Grundlage der Warme einflus sverbundbeschichtung 10Р6M5 Stahl wahrend der Vakuumbelichtungsgepulster Elektronenstrah

Mine closure of pit lakes as terminal sinks: best available practice when options are limited?

In an arid climate, pit lake evaporation rates can exceed influx rates, causing the lake to function as a hydraulic terminal sink, with water levels in the pit remaining below surrounding groundwater levels. We present case studies from Western Australia for two mines nearing closure. At the first site, modelling indicates that waste dump covers for the potentially acid forming (PAF) material would not be successful over the long term (1,000 years or more). The second site is a case study where PAF management is limited by the current waste rock dump location and suitable cover materials. Pit lake water balance modelling using Goldsim software indicated that both pit lakes would function as hydraulic terminal sinks if not backfilled above long-term equilibrium water levels. Poor water quality will likely develop as evapoconcentration increases contaminant concentrations, providing a potential threat to local wildlife. Even so, the best current opportunity to limit the risk of contaminant migration and protect regional groundwater environments may be to limit backfill and intentionally produce a terminal sink pit lake

Mosaic Origins of a Complex Chimeric Mitochondrial Gene in Silene vulgaris

Chimeric genes are significant sources of evolutionary innovation that are normally created when portions of two or more protein coding regions fuse to form a new open reading frame. In plant mitochondria astonishingly high numbers of different novel chimeric genes have been reported, where they are generated through processes of rearrangement and recombination. Nonetheless, because most studies do not find or report nucleotide variation within the same chimeric gene, evolution after the origination of these chimeric genes remains unstudied. Here we identify two alleles of a complex chimera in Silene vulgaris that are divergent in nucleotide sequence, genomic position relative to other mitochondrial genes, and expression patterns. Structural patterns suggest a history partially influenced by gene conversion between the chimeric gene and functional copies of subunit 1 of the mitochondrial ATP synthase gene (atp1). We identified small repeat structures within the chimeras that are likely recombination sites allowing generation of the chimera. These results establish the potential for chimeric gene divergence in different plant mitochondrial lineages within the same species. This result contrasts with the absence of diversity within mitochondrial chimeras found in crop species

Sequence Analysis of the Genome of an Oil-Bearing Tree, Jatropha curcas L.

The whole genome of Jatropha curcas was sequenced, using a combination of the conventional Sanger method and new-generation multiplex sequencing methods. Total length of the non-redundant sequences thus obtained was 285 858 490 bp consisting of 120 586 contigs and 29 831 singlets. They accounted for ∼95% of the gene-containing regions with the average G + C content was 34.3%. A total of 40 929 complete and partial structures of protein encoding genes have been deduced. Comparison with genes of other plant species indicated that 1529 (4%) of the putative protein-encoding genes are specific to the Euphorbiaceae family. A high degree of microsynteny was observed with the genome of castor bean and, to a lesser extent, with those of soybean and Arabidopsis thaliana. In parallel with genome sequencing, cDNAs derived from leaf and callus tissues were subjected to pyrosequencing, and a total of 21 225 unigene data have been generated. Polymorphism analysis using microsatellite markers developed from the genomic sequence data obtained was performed with 12 J. curcas lines collected from various parts of the world to estimate their genetic diversity. The genomic sequence and accompanying information presented here are expected to serve as valuable resources for the acceleration of fundamental and applied research with J. curcas, especially in the fields of environment-related research such as biofuel production. Further information on the genomic sequences and DNA markers is available at http://www.kazusa.or.jp/jatropha/