Effect of terbutaline on hyperpnoea-induced bronchoconstriction and urinary club cell protein 16 in athletes

This article is made available through the Brunel Open Access Publishing Fund and is distributed by the Creative Commons CC-BY 3.0 license, under which all are free to reuse or distribute the article under the condition that this original publication must be cited.Repeated injury of the airway epithelium caused by hyperpnoea of poorly conditioned air has been proposed as a key factor in the pathogenesis of exercise-induced bronchoconstriction (EIB) in athletes. In animals, the short-acting β2-agonist terbutaline has been shown to reduce dry airflow-induced bronchoconstriction and the associated shedding of airway epithelial cells. Our aim was to test the efficacy of inhaled terbutaline in attenuating hyperpnoea-induced bronchoconstriction and airway epithelial injury in athletes. Twenty-seven athletes with EIB participated in a randomized, double-blind, placebo-controlled, crossover study. Athletes completed an 8-min eucapnic voluntary hyperpnoea (EVH) test with dry air on two separate days 15 min after inhaling 0.5 mg terbutaline or a matching placebo. Forced expiratory volume in 1 s (FEV1) and urinary concentration of the club cell (Clara cell) protein 16 (CC16, a marker of airway epithelial perturbation) were measured before and up to 60 min after EVH. The maximum fall in FEV1 of 17 ± 8% (SD) on placebo was reduced to 8 ± 5% following terbutaline (P < 0.001). Terbutaline gave bronchoprotection (i.e., post-EVH FEV1 fall <10%) to 22 (81%) athletes. EVH caused an increase in urinary excretion of CC16 in both conditions (P < 0.001), and terbutaline significantly reduced this rise (pre- to postchallenge CC16 increase 416 ± 495 pg/μmol creatinine after placebo vs. 315 ± 523 pg/μmol creatinine after terbutaline, P = 0.016). These results suggest that the inhalation of a single therapeutic dose of terbutaline offers significant protection against hyperpnoea-induced bronchoconstriction and attenuates acute airway epithelial perturbation in athletes.World Anti Doping Agenc

Cognitive architectures as Lakatosian research programmes: two case studies

Cognitive architectures - task-general theories of the structure and function of the complete cognitive system - are sometimes argued to be more akin to frameworks or belief systems than scientific theories. The argument stems from the apparent non-falsifiability of existing cognitive architectures. Newell was aware of this criticism and argued that architectures should be viewed not as theories subject to Popperian falsification, but rather as Lakatosian research programs based on cumulative growth. Newell's argument is undermined because he failed to demonstrate that the development of Soar, his own candidate architecture, adhered to Lakatosian principles. This paper presents detailed case studies of the development of two cognitive architectures, Soar and ACT-R, from a Lakatosian perspective. It is demonstrated that both are broadly Lakatosian, but that in both cases there have been theoretical progressions that, according to Lakatosian criteria, are pseudo-scientific. Thus, Newell's defense of Soar as a scientific rather than pseudo-scientific theory is not supported in practice. The ACT series of architectures has fewer pseudo-scientific progressions than Soar, but it too is vulnerable to accusations of pseudo-science. From this analysis, it is argued that successive versions of theories of the human cognitive architecture must explicitly address five questions to maintain scientific credibility

Six-Month Mortality among HIV-Infected Adults Presenting for Antiretroviral Therapy with Unexplained Weight Loss, Chronic Fever or Chronic Diarrhea in Malawi.

In sub-Saharan Africa, early mortality is high following initiation of antiretroviral therapy (ART). We investigated 6-month outcomes and factors associated with mortality in HIV-infected adults being assessed for ART initiation and presenting with weight loss, chronic fever or diarrhea, and with negative TB sputum microscopy

Modular differential equations for characters of RCFT

We discuss methods, based on the theory of vector-valued modular forms, to determine all modular differential equations satisfied by the conformal characters of RCFT; these modular equations are related to the null vector relations of the operator algebra. Besides describing effective algorithmic procedures, we illustrate our methods on an explicit example.Comment: 13 page

A standard, single dose of inhaled terbutaline attenuates hyperpnoea-induced bronchoconstriction and mast cell activation in athletes

Release of broncho-active mediators from mast cells during exercise hyperpnoea is a key factor in the pathophysiology of exercise-induced bronchoconstriction (EIB). Our aim was to investigate the effect of a standard, single dose of an inhaled β2-adrenoceptor agonist on mast cell activation in response to dry air hyperpnoea in athletes with EIB. Twenty-seven athletes with EIB completed a randomised, double blind, placebo-controlled, crossover study. Terbutaline (0.5 mg) or placebo was inhaled15 min prior to 8 min of eucapnic voluntary hyperpnoea (EVH) with dry air. Pre- and post-bronchial challenge, urine samples were analysed by enzyme immunoassay for 11β-prostaglandin(PG)F2α. The maximum fall in forced expiratory volume in 1 sec(FEV1) of 14 (12-20)% (median and interquartile range) following placebo was attenuated to 7 (5-9)% with the administration of terbutaline (P<0.001). EVH caused a significant increase in 11β-PGF2α from (27-57) ng·mmol creatinine-1 at baseline to (43-72) ng·mmol creatinine-1 at its peak post-EVH following placebo (P=0.002). The rise in 11β-PGF2α was inhibited with administration of terbutaline: 39 (28-44) ng·mmol creatinine-1 at baseline vs. 40 (33-58) ng·mmol creatinine-1 at its peak post-EVH (P=0.118). These data provide novel in vivo evidence of mast cell stabilisation following inhalation of a standard dose of terbutaline prior to bronchial provocation with EVH in athletes with EIB

Cognitive appraisal of environmental stimuli induces emotion-like states in fish

The occurrence of emotions in non-human animals has been the focus of debate over the years. Recently, an interest in expanding this debate to non-tetrapod vertebrates and to invertebrates has emerged. Within vertebrates, the study of emotion in teleosts is particularly interesting since they represent a divergent evolutionary radiation from that of tetrapods, and thus they provide an insight into the evolution of the biological mechanisms of emotion. We report that Sea Bream exposed to stimuli that vary according to valence (positive, negative) and salience (predictable, unpredictable) exhibit different behavioural, physiological and neuromolecular states. Since according to the dimensional theory of emotion valence and salience define a two-dimensional affective space, our data can be interpreted as evidence for the occurrence of distinctive affective states in fish corresponding to each the four quadrants of the core affective space. Moreover, the fact that the same stimuli presented in a predictable vs. unpredictable way elicited different behavioural, physiological and neuromolecular states, suggests that stimulus appraisal by the individual, rather than an intrinsic characteristic of the stimulus, has triggered the observed responses. Therefore, our data supports the occurrence of emotion-like states in fish that are regulated by the individual's perception of environmental stimuli.European Commission [265957 Copewell]; Fundacao para a Ciencia e Tecnologia [SFRH/BD/80029/2011, SFRH/BPD/72952/2010]info:eu-repo/semantics/publishedVersio

Quantifying The Causes of Differences in Tropospheric OH within Global Models

The hydroxyl radical (OH) is the primary daytime oxidant in the troposphere and provides the main loss mechanism for many pollutants and greenhouse gases, including methane (CH4). Global mean tropospheric OH differs by as much as 80% among various global models, for reasons that are not well understood. We use neural networks (NNs), trained using archived output from eight chemical transport models (CTMs) that participated in the POLARCAT Model Intercomparison Project (POLMIP), to quantify the factors responsible for differences in tropospheric OH and resulting CH4 lifetime (τCH4) between these models. Annual average τCH4, for loss by OH only, ranges from 8.0–11.6 years for the eight POLMIP CTMs. The factors driving these differences were quantified by inputting 3-D chemical fields from one CTM into the trained NN of another CTM. Across all CTMs, the largest mean differences in τCH4 (ΔτCH4) result from variations in chemical mechanisms (ΔτCH4 = 0.46 years), the photolysis frequency (J) of O3→O(1D) (0.31 years), local O3 (0.30 years), and CO (0.23 years). The ΔτCH4 due to CTM differences in NOx (NO + NO2) is relatively low (0.17 years), though large regional variation in OH between the CTMs is attributed to NOx. Differences in isoprene and J(NO2) have negligible overall effect on globally averaged tropospheric OH, though the extent of OH variations due to each factor depends on the model being examined. This study demonstrates that NNs can serve as a useful tool for quantifying why tropospheric OH varies between global models, provided essential chemical fields are archived

Towards quantum computing with single atoms and optical cavities on atom chips

We report on recent developments in the integration of optical microresonators into atom chips and describe some fabrication and implementation challenges. We also review theoretical proposals for quantum computing with single atoms based on the observation of photons leaking through the cavity mirrors. The use of measurements to generate entanglement can result in simpler, more robust and scalable quantum computing architectures. Indeed, we show that quantum computing with atom-cavity systems is feasible even in the presence of relatively large spontaneous decay rates and finite photon detector efficiencies.Comment: 14 pages, 6 figure

The validity of using ICD-9 codes and pharmacy records to identify patients with chronic obstructive pulmonary disease

Background: Administrative data is often used to identify patients with chronic obstructive pulmonary disease (COPD), yet the validity of this approach is unclear. We sought to develop a predictive model utilizing administrative data to accurately identify patients with COPD. Methods: Sequential logistic regression models were constructed using 9573 patients with postbronchodilator spirometry at two Veterans Affairs medical centers (2003-2007). COPD was defined as: 1) FEV1/FVC <0.70, and 2) FEV1/FVC < lower limits of normal. Model inputs included age, outpatient or inpatient COPD-related ICD-9 codes, and the number of metered does inhalers (MDI) prescribed over the one year prior to and one year post spirometry. Model performance was assessed using standard criteria. Results: 4564 of 9573 patients (47.7%) had an FEV1/FVC < 0.70. The presence of ≥1 outpatient COPD visit had a sensitivity of 76% and specificity of 67%; the AUC was 0.75 (95% CI 0.74-0.76). Adding the use of albuterol MDI increased the AUC of this model to 0.76 (95% CI 0.75-0.77) while the addition of ipratropium bromide MDI increased the AUC to 0.77 (95% CI 0.76-0.78). The best performing model included: ≥6 albuterol MDI, ≥3 ipratropium MDI, ≥1 outpatient ICD-9 code, ≥1 inpatient ICD-9 code, and age, achieving an AUC of 0.79 (95% CI 0.78-0.80). Conclusion: Commonly used definitions of COPD in observational studies misclassify the majority of patients as having COPD. Using multiple diagnostic codes in combination with pharmacy data improves the ability to accurately identify patients with COPD.Department of Veterans Affairs, Health Services Research and Development (DHA), American Lung Association (CI- 51755-N) awarded to DHA, the American Thoracic Society Fellow Career Development AwardPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/84155/1/Cooke - ICD9 validity in COPD.pd

Screening of DUB activity and specificity by MALDI-TOF mass spectrometry

Deubiquitylases (DUBs) are key regulators of the ubiquitin system which cleave ubiquitin moieties from proteins and polyubiquitin chains. Several DUBs have been implicated in various diseases and are attractive drug targets. We have developed a sensitive and fast assay to quantify in vitro DUB enzyme activity using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Unlike other current assays, this method uses unmodified substrates, such as diubiquitin topoisomers. By analyzing 42 human DUBs against all diubiquitin topoisomers we provide an extensive characterization of DUB activity and specificity. Our results confirm the high specificity of many members of the OTU and JAMM DUB families and highlight that all USPs tested display low linkage selectivity. We also demonstrate that this assay can be deployed to assess the potency and specificity of DUB inhibitors by profiling 11 compounds against a panel of 32 DUBs