P17 Dietary nitrate supplementation increases fractional exhaled nitric oxide : implications for the assessment of airway health in athletes

Background: Fractional exhaled nitric oxide (FeNO) is a simple tool that has an established role in the assessment of airway inflammation in athletes. Specifically, FeNO provides information concerning asthma phenotypes, aetiology of respiratory symptoms, response to anti-inflammatory agents, course of disease and adherence to medication. It is recognised that FeNO can be influenced by a variety of external factors (e.g. atopic status, exercise, respiratory tract infection), however, there remains limited research concerning the impact of dietary nitrate ingestion. The primary aim of this study was therefore to evaluate the effect of acute dietary nitrate supplementation on FeNO and resting pulmonary function parameters. Method: The study was conducted as a randomised double-blind placebo-controlled trial. Thirty male endurance trained athletes (age: 28 ± 6 yrs; BMI: 23 ± 2 kg.m-2) free from cardio-respiratory and metabolic disease, and stable at time of study entry (i.e. entirely asymptomatic without recent respiratory tract infection) attended the laboratory on two separate occasions. On arrival to the laboratory, athletes consumed either 140ml nitrate-rich beetroot juice (15.2 mmol nitrate) (NIT) or nitrate-depleted beetroot juice (0 mmol nitrate) (PLA). In accordance with international guidelines all athletes performed resting FeNO and forced spirometry (2.5hrs post ingestion). Airway inflammation was evaluated using established FeNO thresholds: (intermediate [≥25ppb] and high [>50ppb]). Results: All athletes demonstrated normal baseline lung function (FEV1 % predicted >80%). A three-fold rise in resting FeNO was observed following NIT (median [IQR]): 32ppb [37] in comparison to PLA: 10ppb [12] (P0.05). Conclusion: Dietary nitrate ingestion should be considered when employing FeNO for the assessment of airway health in athletes. Our findings have implications concerning the decision to initiate or modify inhaler therapy. Further research is therefore required to determine the impact of chronic dietary nitrate ingestion on pulmonary function and bronchoprovocation testing in athletes with pre-existing asthma and/or exercise-induced bronchoconstriction

Eucapnic Voluntary Hyperpnea Testing in Asymptomatic Athletes.

Letter to the Edito

Pricing Exotic Options in a Path Integral Approach

In the framework of Black-Scholes-Merton model of financial derivatives, a path integral approach to option pricing is presented. A general formula to price European path dependent options on multidimensional assets is obtained and implemented by means of various flexible and efficient algorithms. As an example, we detail the cases of Asian, barrier knock out, reverse cliquet and basket call options, evaluating prices and Greeks. The numerical results are compared with those obtained with other procedures used in quantitative finance and found to be in good agreement. In particular, when pricing at-the-money and out-of-the-money options, the path integral approach exhibits competitive performances.Comment: 21 pages, LaTeX, 3 figures, 6 table

Wikipedia as an encyclopaedia of life

In his 2003 essay E O Wilson outlined his vision for an “encyclopaedia of life” comprising “an electronic page for each species of organism on Earth”, each page containing “the scientific name of the species, a pictorial or genomic presentation of the primary type specimen on which its name is based, and a summary of its diagnostic traits.” Although the “quiet revolution” in biodiversity informatics has generated numerous online resources, including some directly inspired by Wilson's essay (e.g., "http://ispecies.org":http://ispecies.org, "http://www.eol.org":http://www.eol.org), we are still some way from the goal of having available online all relevant information about a species, such as its taxonomy, evolutionary history, genomics, morphology, ecology, and behaviour. While the biodiversity community has been developing a plethora of databases, some with overlapping goals and duplicated content, Wikipedia has been slowly growing to the point where it now has over 100,000 pages on biological taxa. My goal in this essay is to explore the idea that, largely independent of the efforts of biodiversity informatics and well-funded international efforts, Wikipedia ("http://en.wikipedia.org/wiki/Main_Page":http://en.wikipedia.org/wiki/Main_Page) has emerged as potentially the best platform for fulfilling E O Wilson’s vision

The local symmetries of M-theory and their formulation in generalised geometry

In the doubled field theory approach to string theory, the T-duality group is promoted to a manifest symmetry at the expense of replacing ordinary Riemannian geometry with generalised geometry on a doubled space. The local symmetries are then given by a generalised Lie derivative and its associated algebra. This paper constructs an analogous structure for M-theory. A crucial by-product of this is the derivation of the physical section condition for M-theory formulated in an extended space.Comment: 20 pages, v2: Author Name corrected, v3: typos correcte

Vortex deformation and breaking in superconductors: A microscopic description

Vortex breaking has been traditionally studied for nonuniform critical current densities, although it may also appear due to nonuniform pinning force distributions. In this article we study the case of a high-pinning/low-pinning/high-pinning layered structure. We have developed an elastic model for describing the deformation of a vortex in these systems in the presence of a uniform transport current density $J$ for any arbitrary orientation of the transport current and the magnetic field. If $J$ is above a certain critical value, $J_c$, the vortex breaks and a finite effective resistance appears. Our model can be applied to some experimental configurations where vortex breaking naturally exists. This is the case for YBa$_2$Cu$_3$O$_{7-x}$ (YBCO) low angle grain boundaries and films on vicinal substrates, where the breaking is experienced by Abrikosov-Josephson vortices (AJV) and Josephson string vortices (SV), respectively. With our model, we have experimentally extracted some intrinsic parameters of the AJV and SV, such as the line tension $\epsilon_l$ and compared it to existing predictions based on the vortex structure.Comment: 11 figures in 13 files; minor changes after printing proof

Four patients with a history of acute exacerbations of COPD: implementing the CHEST/Canadian Thoracic Society guidelines for preventing exacerbations

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Allelic Exchange of Pheromones and Their Receptors Reprograms Sexual Identity in Cryptococcus neoformans

Cell type specification is a fundamental process that all cells must carry out to ensure appropriate behaviors in response to environmental stimuli. In fungi, cell identity is critical for defining “sexes” known as mating types and is controlled by components of mating type (MAT) loci. MAT–encoded genes function to define sexes via two distinct paradigms: 1) by controlling transcription of components common to both sexes, or 2) by expressing specially encoded factors (pheromones and their receptors) that differ between mating types. The human fungal pathogen Cryptococcus neoformans has two mating types (a and α) that are specified by an extremely unusual MAT locus. The complex architecture of this locus makes it impossible to predict which paradigm governs mating type. To identify the mechanism by which the C. neoformans sexes are determined, we created strains in which the pheromone and pheromone receptor from one mating type (a) replaced the pheromone and pheromone receptor of the other (α). We discovered that these “αa” cells effectively adopt a new mating type (that of a cells); they sense and respond to α factor, they elicit a mating response from α cells, and they fuse with α cells. In addition, αa cells lose the α cell type-specific response to pheromone and do not form germ tubes, instead remaining spherical like a cells. Finally, we discovered that exogenous expression of the diploid/dikaryon-specific transcription factor Sxi2a could then promote complete sexual development in crosses between α and αa strains. These data reveal that cell identity in C. neoformans is controlled fully by three kinds of MAT–encoded proteins: pheromones, pheromone receptors, and homeodomain proteins. Our findings establish the mechanisms for maintenance of distinct cell types and subsequent developmental behaviors in this unusual human fungal pathogen

Ethanol reversal of tolerance to the respiratory depressant effects of morphine

Opioids are the most common drugs associated with unintentional drug overdose. Death results from respiratory depression. Prolonged use of opioids results in the development of tolerance but the degree of tolerance is thought to vary between different effects of the drugs. Many opioid addicts regularly consume alcohol (ethanol), and post-mortem analyses of opioid overdose deaths have revealed an inverse correlation between blood morphine and ethanol levels. In the present study, we determined whether ethanol reduced tolerance to the respiratory depressant effects of opioids. Mice were treated with opioids (morphine, methadone, or buprenorphine) for up to 6 days. Respiration was measured in freely moving animals breathing 5% CO(2) in air in plethysmograph chambers. Antinociception (analgesia) was measured as the latency to remove the tail from a thermal stimulus. Opioid tolerance was assessed by measuring the response to a challenge dose of morphine (10 mg/kg i.p.). Tolerance developed to the respiratory depressant effect of morphine but at a slower rate than tolerance to its antinociceptive effect. A low dose of ethanol (0.3 mg/kg) alone did not depress respiration but in prolonged morphine-treated animals respiratory depression was observed when ethanol was co-administered with the morphine challenge. Ethanol did not alter the brain levels of morphine. In contrast, in methadone- or buprenorphine-treated animals no respiratory depression was observed when ethanol was co-administered along with the morphine challenge. As heroin is converted to morphine in man, selective reversal of morphine tolerance by ethanol may be a contributory factor in heroin overdose deaths