Non-invasive biomarkers and pulmonary function in smokers

Limited information exists regarding measurement, reproducibility and interrelationships of non-invasive biomarkers in smokers. We compared exhaled breath condensate (EBC) leukotriene B4 (LTB4) and 8-isoprostane, exhaled nitric oxide, induced sputum, spirometry, plethysmography, impulse oscillometry and methacholine reactivity in 18 smokers and 10 non-smokers. We assessed the relationships between these measurements and within-subject reproducibility of EBC biomarkers in smokers. Compared to non-smokers, smokers had significantly lower MMEF % predicted (mean 64.1 vs 77.7, p = 0.003), FEV1/FVC (mean 76.2 vs 79.8 p = 0.05), specific conductance (geometric mean 1.2 vs 1.6, p = 0.02), higher resonant frequency (mean 15.5 vs 9.9, p = 0.01) and higher EBC 8-isoprostane (geometric mean 49.9 vs 8.9 pg/ml p = 0.001). Median EBC pH values were similar, but a subgroup of smokers had airway acidification (pH < 7.2) not observed in non-smokers. Smokers had predominant sputum neutrophilia (mean 68.5%). Repeated EBC measurements showed no significant differences between group means, but Bland Altman analysis showed large individual variability. EBC 8-isoprostane correlated with EBC LTB4 (r = 0.78, p = 0.0001). Sputum supernatant IL-8 correlated with total neutrophil count per gram of sputum (r = 0.52, p = 0.04) and with EBC pH (r = −0.59, p = 0.02). In conclusion, smokers had evidence of small airway dysfunction, increased airway resistance, reduced lung compliance, airway neutrophilia and oxidative stress

Sodium transport and attenuation in soil cover materials for oil sands mine reclamation

0883-2927/ © 2018 Elsevier Ltd. All rights reserved.Funding was provided to MBJL by the Natural Sciences and Engineering Council of Canada (NSERC) and Syncrude Canada Ltd. through the Industrial Research Chairs program (Grant No. IRCPJ 450684−13). Additional support awarded to CVJ through the Brian and Elaine Russel Undergraduate Research Fund and the NSERC Canadian Graduate Scholarships – Master’s (NSERC CGS-M) Program.Peer ReviewedReclamation soil covers are used in oil sands mine closure to support vegetative growth over tailings. Geochemical processes within these covers may impact solute transport during upward migration of oil sands process-affected water (OSPW) from the underlying tailings. In this study, we examined the geochemical processes controlling Na transport and attenuation within the peat and clay-till cover soils at Sandhill Fen in northern Alberta, Canada. We analyzed soil core samples collected along transects of this 54-ha pilot-scale oil sands mine reclamation wetland. The geochemical (Na, Ca, Mg, K, Cl, SO4, HCO3) and isotopic (δ2H, δ18O) compositions of extracted pore water were analyzed statistically to identify OSPW and fresh surface water within the cover. Depth-dependent trends in pore water sodium concentrations were not apparent, suggesting that the soil cover had been fully flushed by a mixture of OSPW and fresh surface water used to flood the fen. Relative concentrations of Na, Ca and Mg were used to define the extent of cation exchange within the clay cover. Complementary laboratory column experiments showed that cation exchange removed up to 50% of dissolved Na as the first pore volume of simulated OSPW passed through the peat and till. However, Na attenuation by these materials declined rapidly and was limited after 4 (peat) to 7 (till) pore volumes of OSPW flushing. Reactive transport modeling confirmed that cation exchange was the dominant control on Na attenuation and corresponding Ca and Mg release within the till and peat columns. Mineral precipitation-dissolution reactions also influenced dissolved Ca and Mg concentrations and, therefore, indirectly impacted Na attenuation. Overall, this study helps constrain the geochemical processes controlling Na transport and attenuation in oil sands reclamation soil covers exposed to OSPW, and indicates that the attenuation of Na from OSPW by these covers is short-lived

A methodology for the capture and analysis of hybrid data: a case study of program debugging

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The effects of childbirth on the pelvic-floor

Basically, vaginal delivery is associated with the risk of pelvic floor damage. The pelvic floor sequelae of childbirth includes anal incontinence, urinary incontinence and pelvic organ prolapse. Pathophysiology, incidence and risk factors for the development of the respective problems are reviewed. Where possible, recommendations for reducing the risk of pelvic floor damage are given

A Sphingosine Kinase Form 2 Knockout Sensitizes Mouse Myocardium to Ischemia/Reoxygenation Injury and Diminishes Responsiveness to Ischemic Preconditioning

Sphingosine kinase (SphK) exhibits two isoforms, SphK1 and SphK2. Both forms catalyze the synthesis of sphingosine 1-phosphate (S1P), a sphingolipid involved in ischemic preconditioning (IPC). Since the ratio of SphK1 : SphK2 changes dramatically with aging, it is important to assess the role of SphK2 in IR injury and IPC. Langendorff mouse hearts were subjected to IR (30 min equilibration, 50 min global ischemia, and 40 min reperfusion). IPC consisted of 2 min of ischemia and 2 min of reperfusion for two cycles. At baseline, there were no differences in left ventricular developed pressure (LVDP), ± dP/dtmax, and heart rate between SphK2 null (KO) and wild-type (WT) hearts. In KO hearts, SphK2 activity was undetectable, and SphK1 activity was unchanged compared to WT. Total SphK activity was reduced by 53%. SphK2 KO hearts subjected to IR exhibited significantly more cardiac damage (37 ± 1% infarct size) compared with WT (28 ± 1% infarct size); postischemic recovery of LVDP was lower in KO hearts. IPC exerted cardioprotection in WT hearts. The protective effect of IPC against IR was diminished in KO hearts which had much higher infarction sizes (35 ± 2%) compared to the IPC/IR group in control hearts (12 ± 1%). Western analysis revealed that KO hearts had substantial levels of phosphorylated p38 which could predispose the heart to IR injury. Thus, deletion of the SphK2 gene sensitizes the myocardium to IR injury and diminishes the protective effect of IPC

Validation of the Human Ozone Challenge Model as a Tool for Assessing Anti-Inflammatory Drugs in Early Development

This study aimed to test the utility of the ozone challenge model for profiling novel compounds designed to reduce airway inflammation. The authors used a randomized, doubledummy, double-blind, placebo-controlled 3-period crossover design alternating single orally inhaled doses of fluticasone propionate (inhaled corticosteroids, 2mg), oral prednisolone (oral corticosteroids, 50mg), ormatched placebo. At a 2-week interval, 18 healthy ozone responders (>10% increase in sputum neutrophils) underwent a 3-hour ozone (250 ppb)/intermittent exercise challenge starting 1 hour after drug treatment. Airway inflammation was assessed at 2 hours (breath condensate) and 3 hours (induced sputum) after ozone challenge. Compared to placebo, pretreatment with inhaled corticosteroids or oral corticosteroids resulted in a significant reduction (mean [95% confidence interval]) of sputum neutrophils by 62% (35%, 77%) and 64% (39%, 79%) and of sputum supernatant myeloperoxidase by 55% (41%, 66%) and 42% (25%, 56%), respectively. The authors conclude that an optimized ozone challenge model (including ozone responders and ensuring adequate drug levels during exposure) may be useful for testing novel anti-inflammatory compounds in early development

Sindarin: A Versatile Scripting API for the Pharo Debugger

International audienceDebugging is one of the most important and time consuming activities in software maintenance, yet mainstream debuggers are not well-adapted to several debugging scenarios. This has led to the research of new techniques covering specific families of complex bugs. Notably, recent research proposes to empower developers with scripting DSLs, plugin-based and moldable debuggers. However, these solutions are tailored to specific use-cases, or too costly for one-time-use scenarios. In this paper we argue that exposing a debugging scripting interface in mainstream debuggers helps in solving many challenging debugging scenarios. For this purpose, we present Sindarin, a scripting API that eases the expression and automation of different strategies developers pursue during their debugging sessions. Sindarin provides a GDB-like API, augmented with AST-bytecode-source code mappings and object-centric capabilities. To demonstrate the versatility of Sindarin, we reproduce several advanced breakpoints and non-trivial debugging mechanisms from the literature

Cognitive Aspects of Structured Process Modeling

After visualizing data of various observational experiments on the way in which modelers construct process models, a promising process modeling style (i.e., structured process modeling) was discovered that is expected to cause process model quality to increase. A modeler constructs process models in a structured way if she/he is working on few parts of the model simultaneously. This paper describes cognitive theories that can explain this causal relation. Cognitive Load Theory (CLT) suggests that the amount of errors increases when the limited capacity of our working memory is overloaded. Cognitive Fit Theory (CFT) states that performance is improved when task material representation matches with the task to be executed. Three hypotheses are formulated and the experimental set-up to evaluate these hypotheses is described

A survey in rural China of parent-absence through migrant working: the impact on their children's self-concept and loneliness

<p>Abstract</p> <p>Background</p> <p>Following the rapid increase of migrant workers in China, the number of "absent migrant parents" children is also rising fast. The "absent migrant parents" children might have an insecure relationship with their parents, have a different view of them, and be prone to have the feeling of loneliness. The purpose of the study was to compare the self-concept and loneliness between the "absent migrant parents" children and comparison children, to examine the relationship between self-concept and loneliness among the two groups, and to study the predictors of self-concept among the two groups.</p> <p>Methods</p> <p>Participants were 230 "absent migrant parents" children and 250 comparison children in the rural area of a county, China. The self-concept and loneliness of children were assessed using Piers-Harris Self-Concept Scale and Childhood Loneliness Scale.</p> <p>Results</p> <p>The "absent migrant parents" children were more likely to dislike their parents or be uncertain whether they like their parents, and they reported less time spent in physical and leisure time activities, higher loneliness and lower self-concept in comparison with the comparison children. Loneliness was significantly negatively correlated with all the dimensions of self-concept among the two groups. Regression analysis showed that self-concept was positively related to the relationship with parents and guardians and time spent in physical and leisure activities among the "absent migrant parents" children. The same factors (except the relationship with guardians) were found for self-concept among the comparison children.</p> <p>Conclusions</p> <p>The "absent migrant parents" children were more inclined to have lower self-concept and higher loneliness. The lower self-concept seemed to contribute to the higher loneliness of the "absent migrant parents" children. The lower self-concept of the "absent migrant parents" children was mainly related with their relationship with parents and guardians. The acceptance and support from their parents could not be fully replaced by that from their guardians.</p