Efficacy of salbutamol via Easyhaler®unaffected by low inspiratory flow

AbstractThe fine particle dose delivered via dry powder inhalers (DPIs) is often affected by the inspiratory flow rate generated during inhalation. This has clinical implications, since the fine particle dose determines the amount of drug reaching the lungs. With Easyhaler®DPI the fine particle dose remains relatively constant over the range of inspiratory flow rates from 30–60 l min−1. The aim of this study was to confirm that clinical efficacy is maintained even at low flow rates by comparing the bronchodilating effect of salbutamol (100 μ g) delivered via Easyhaler®at a target inspiratory flow of 30 l min−1with the same dose of salbutamol via pressurised metered-dose inhaler (pMDI) plus spacer.This was a double-blind, randomized, cross-over study with double-dummy technique. Twenty-one paediatric and adult asthmatic patients completed the study, which was conducted over 2 study days. The main outcome parameter was forced expiratory volume in 1 sec (FEV1). The patients were trained to generate a low peak inspiratory flow rate (PIFR) of 30 l min−1, and the actual PIFR through Easyhaler®was recorded.The average PIFR through Easyhaler®was 28·7 l min−1. The difference in the maximum value of FEV1(FEV1max) between the treatments after drug inhalation was 0·01 l. The mean of FEV1maxwas 2·67 l after pMDI plus spacer compared to 2·69 l after Easyhaler®. Improvements in FEV1were clinically significant. No significant differences between treatments were found.A reasonably low inspiratory flow rate through Easyhaler®produces an equivalent improvement in lung function to a correctly used pMDI plus spacer. Hence, Easyhaler®can be used with confidence in patients who may have difficulty in generating a high inspiratory flow rate, such as children and the elderly

Temperature dependence of the Brewer global UV measurements

Spectral measurements of global UV irradiance recorded by Brewer spectrophotometers can be significantly affected by instrument-specific optical and mechanical features. Thus, proper corrections are needed in order to reduce the associated uncertainties to within acceptable levels. The present study aims to contribute to the reduction of uncertainties originating from changes in the Brewer internal temperature, which affect the performance of the optical and electronic parts, and subsequently the response of the instrument. Until now, measurements of the irradiance from various types of lamps at different temperatures have been used to characterize the instruments' temperature dependence. The use of 50 W lamps was found to induce errors in the characterization due to changes in the transmissivity of the Teflon diffuser as it warms up by the heat of the lamp. In contrast, the use of 200 or 1000 W lamps is considered more appropriate because they are positioned at longer distances from the diffuser so that warming is negligible. Temperature gradients inside the instrument can cause mechanical stresses which can affect the instrument's optical characteristics. Therefore, during the temperature-dependence characterization procedure warming or cooling must be slow enough to minimize these effects. In this study, results of the temperature characterization of eight different Brewer spectrophotometers operating in Greece, Finland, Germany and Spain are presented. It was found that the instruments' response changes differently in different temperature regions due to different responses of the diffusers' transmittance. The temperature correction factors derived for the Brewer spectrophotometers operating at Thessaloniki, Greece, and Sodankylä, Finland, were evaluated and were found to remove the temperature dependence of the instruments' sensitivity.This article is based upon work from COST Action ES1207 “A European Brewer Network (EUBREWNET)”, supported by COST (European Cooperation in Science and Technology) and from the ENV59-ATMOZ (“Traceability for atmospheric total column ozone”) Joint Research Programme (JRP)

The identification and analysis of making-do waste: insights from two Brazilian construction sites

Making-do has been pointed out as an important category of waste in the construction industry. It refers to a situation in which a task starts or continues without having available all the inputs required for its completion, such as materials, machinery, tools, personnel, external conditions, and information. By contrast, the literature points out that improvisation is a ubiquitous human practice even in highly structured business organizations, and plays an important role when rules and methods fail. The aim of this paper is to provide some insights on the nature of making-do as a type of waste, based on two exploratory case studies carried out on construction sites. The main contributions of this research work are concerned with the identification of different categories of making-do and its main causes. This paper also discusses some strategies for reducing making-do on construction sites

Genomic prediction of relapse in recipients of allogeneic haematopoietic stem cell transplantation

Allogeneic haematopoietic stem cell transplantation currently represents the primary potentially curative treatment for cancers of the blood and bone marrow. While relapse occurs in approximately 30% of patients, few risk-modifying genetic variants have been identified. The present study evaluates the predictive potential of patient genetics on relapse risk in a genome-wide manner. We studied 151 graft recipients with HLA-matched sibling donors by sequencing the whole-exome, active immunoregulatory regions, and the full MHC region. To assess the predictive capability and contributions of SNPs and INDELs, we employed machine learning and a feature selection approach in a cross-validation framework to discover the most informative variants while controlling against overfitting. Our results show that germline genetic polymorphisms in patients entail a significant contribution to relapse risk, as judged by the predictive performance of the model (AUC = 0.72 [95% CI: 0.63–0.81]). Furthermore, the top contributing variants were predictive in two independent replication cohorts (n = 258 and n = 125) from the same population. The results can help elucidate relapse mechanisms and suggest novel therapeutic targets. A computational genomic model could provide a step toward individualized prognostic risk assessment, particularly when accompanied by other data modalities.</p

Computational Analysis of HLA-presentation of Non-synonymous Recipient Mismatches Indicates Effect on the Risk of Chronic Graft-vs.-Host Disease After Allogeneic HSCT

Genetic mismatches in protein coding genes between allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipient and donor can elicit an alloimmunity response via peptides presented by the recipient HLA receptors as minor histocompatibility antigens (mHAs). While the impact of individual mHAs on allo-HSCT outcome such as graft-vs.-host and graft-vs.-leukemia effects has been demonstrated, it is likely that established mHAs constitute only a small fraction of all immunogenic non-synonymous variants. In the present study, we have analyzed the genetic mismatching in 157 exome-sequenced sibling allo-HSCT pairs to evaluate the significance of polymorphic HLA class I associated peptides on clinical outcome. We applied computational mismatch estimation approaches based on experimentally verified HLA ligands available in public repositories, published mHAs, and predicted HLA-peptide affinites, and analyzed their associations with chronic graft-vs.-host disease (cGvHD) grades. We found that higher estimated recipient mismatching consistently increased the risk of severe cGvHD, suggesting that HLA-presented mismatching influences the likelihood of long-term complications in the patient. Furthermore, computational approaches focusing on estimation of HLA-presentation instead of all non-synonymous mismatches indiscriminately may be beneficial for analysis sensitivity and could help identify novel mHAs

Idelalisib sensitivity and mechanisms of disease progression in relapsed TCF3-PBX1 acute lymphoblastic leukemia

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Researchers' experience with project management in health and medical research: Results from a post-project review

<p>Abstract</p> <p>Background</p> <p>Project management is widely used to deliver projects on time, within budget and of defined quality. However, there is little published information describing its use in managing health and medical research projects. We used project management in the <it>Alcohol and Pregnancy Project </it>(2006-2008) <url>http://www.ichr.uwa.edu.au/alcoholandpregnancy</url> and in this paper report researchers' opinions on project management and whether it made a difference to the project.</p> <p>Methods</p> <p>A national interdisciplinary group of 20 researchers, one of whom was the project manager, formed the Steering Committee for the project. We used project management to ensure project outputs and outcomes were achieved and all aspects of the project were planned, implemented, monitored and controlled. Sixteen of the researchers were asked to complete a self administered questionnaire for a post-project review.</p> <p>Results</p> <p>The project was delivered according to the project protocol within the allocated budget and time frame. Fifteen researchers (93.8%) completed a questionnaire. They reported that project management increased the effectiveness of the project, communication, teamwork, and application of the interdisciplinary group of researchers' expertise. They would recommend this type of project management for future projects.</p> <p>Conclusions</p> <p>Our post-project review showed that researchers comprehensively endorsed project management in the <it>Alcohol and Pregnancy Project </it>and agreed that project management had contributed substantially to the research. In future, we will project manage new projects and conduct post-project reviews. The results will be used to encourage continuous learning and continuous improvement of project management, and provide greater transparency and accountability of health and medical research. The use of project management can benefit both management and scientific outcomes of health and medical research projects.</p

Additive QTLs on three chromosomes control flowering time in woodland strawberry (Fragaria vesca L.)

Flowering time is an important trait that affects survival, reproduction and yield in both wild and cultivated plants. Therefore, many studies have focused on the identification of flowering time quantitative trait locus (QTLs) in different crops, and molecular control of this trait has been extensively investigated in model species. Here we report the mapping of QTLs for flowering time and vegetative traits in a large woodland strawberry mapping population that was phenotyped both under field conditions and in a greenhouse after flower induction in the field. The greenhouse experiment revealed additive QTLs in three linkage groups (LG), two on both LG4 and LG7, and one on LG6 that explain about half of the flowering time variance in the population. Three of the QTLs were newly identified in this study, and one co-localized with the previously characterized FvTFL1 gene. An additional strong QTL corresponding to previously mapped PFRU was detected in both field and greenhouse experiments indicating that gene(s) in this locus can control the timing of flowering in different environments in addition to the duration of flowering and axillary bud differentiation to runners and branch crowns. Several putative flowering time genes were identified in these QTL regions that await functional validation. Our results indicate that a few major QTLs may control flowering time and axillary bud differentiation in strawberries. We suggest that the identification of causal genes in the diploid strawberry may enable fine tuning of flowering time and vegetative growth in the closely related octoploid cultivated strawberry.Peer reviewe