Dissipation enhanced vibrational sensing in an olfactory molecular switch.

Motivated by a proposed olfactory mechanism based on a vibrationally activated molecular switch, we study electron transport within a donor-acceptor pair that is coupled to a vibrational mode and embedded in a surrounding environment. We derive a polaron master equation with which we study the dynamics of both the electronic and vibrational degrees of freedom beyond previously employed semiclassical (Marcus-Jortner) rate analyses. We show (i) that in the absence of explicit dissipation of the vibrational mode, the semiclassical approach is generally unable to capture the dynamics predicted by our master equation due to both its assumption of one-way (exponential) electron transfer from donor to acceptor and its neglect of the spectral details of the environment; (ii) that by additionally allowing strong dissipation to act on the odorant vibrational mode, we can recover exponential electron transfer, though typically at a rate that differs from that given by the Marcus-Jortner expression; (iii) that the ability of the molecular switch to discriminate between the presence and absence of the odorant, and its sensitivity to the odorant vibrational frequency, is enhanced significantly in this strong dissipation regime, when compared to the case without mode dissipation; and (iv) that details of the environment absent from previous Marcus-Jortner analyses can also dramatically alter the sensitivity of the molecular switch, in particular, allowing its frequency resolution to be improved.

Statistical cluster analysis of the British Thoracic Society Severe refractory Asthma Registry: clinical outcomes and phenotype stability.

Background: Severe refractory asthma is a heterogeneous disease. We sought to determine statistical clusters from the British Thoracic Society Severe refractory Asthma Registry and to examine cluster-specific outcomes and stability.

Methods: Factor analysis and statistical cluster modelling was undertaken to determine the number of clusters and their membership (N = 349).

Integrated care pathways for airway diseases (AIRWAYS-ICPs).

The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies.

The cost of treating severe refractory asthma in the UK: an economic analysis from the British Thoracic Society Difficult Asthma Registry.

Severe refractory asthma poses a substantial burden in terms of healthcare costs but relatively little is known about the factors which drive these costs. This study uses data from the British Thoracic Society Difficult Asthma Registry (n=596) to estimate direct healthcare treatment costs from an National Health Service perspective and examines factors that explain variations in costs. Annual mean treatment costs among severe refractory asthma patients were £2912 (SD £2212) to £4217 (SD £2449).

Inappropriate prescribing of combination inhalers in Northern Ireland: retrospective cross-sectional cohort study of prescribing practice in primary care.

Background: Asthma management guidelines advocate a stepwise approach to asthma therapy, including the addition of a long-acting bronchodilator to inhaled steroid therapy at step 3. This is almost exclusively prescribed as inhaled combination therapy.

Aims: To examine whether asthma prescribing practice for inhaled combination therapy (inhaled corticosteroid/long-acting β2-agonist (ICS/LABA)) in primary care in Northern Ireland is in line with national asthma management guidelines.

Nasal epithelial cells can act as a physiological surrogate for paediatric asthma studies.

Introduction: Differentiated paediatric epithelial cells can be used to study the role of epithelial cells in asthma. Nasal epithelial cells are easier to obtain and may act as a surrogate for bronchial epithelium in asthma studies. We assessed the suitability of nasal epithelium from asthmatic children to be a surrogate for bronchial epithelium using air-liquid interface cultures.

Increased expression of bronchial epithelial transient receptor potential vanilloid 1 channels in patients with severe asthma.

Background: The airway epithelium is exposed to a range of physical and chemical irritants in the environment that are known to trigger asthma. Transient receptor potential (TRP) cation channels play a central role in sensory responses to noxious physical and chemical stimuli. Recent genetic evidence suggests an involvement of transient receptor potential vanilloid 1 (TRPV1), one member of the vanilloid subfamily of TRP channels, in the pathophysiology of asthma.

Non-adherence in difficult asthma and advances in detection.

Non-adherence to anti-inflammatory therapies is common in patients referred for specialist assessment at difficult-to-treat asthma services. In the difficult asthma setting, non-adherence to treatment is associated with poor baseline asthma control, increased frequency of exacerbations and asthma-related hospitalizations, as well as increased risk of death. Here, we present a review of the current literature surrounding the prevalence and risks of non-adherence in difficult asthma and we report on current methods of measuring treatment adherence and advances in the detection of non-adherence.

Rhinovirus upregulates transient receptor potential channels in a human neuronal cell line: implications for respiratory virus-induced cough reflex sensitivity.

Background: The mechanism underlying respiratory virus-induced cough hypersensitivity is unknown. Upregulation of airway neuronal receptors responsible for sensing physical and chemical stimuli is one possibility, and the transient receptor potential (TRP) channel family are potential candidates. We have used an in vitro model of sensory neurons and human rhinovirus (HRV-16) to study the effect of virus infection on TRP expression.

'SIMPLES': a structured primary care approach to adults with difficult asthma.

The substantial majority of patients with asthma can expect minimal breakthrough symptoms on standard doses of inhaled corticosteroids with or without additional add-on therapies. SIMPLES is a structured primary care approach to the review of a person with uncontrolled asthma which encompasses patient education monitoring, lifestyle and pharmacological management and addressing support needs which will achieve control in most patients. The small group of patients presenting with persistent asthma symptoms despite being prescribed high levels of treatment are often referred to as having 'difficult asthma'.

Relative respiratory syncytial virus cytopathogenesis in upper and lower respiratory tract epithelium.

Rationale: Respiratory syncytial virus (RSV) is a major pathogen that primarily infects airway epithelium. Most infants suffer mild upper respiratory tract (URT) symptoms, whereas approximately one-third progress to lower respiratory tract (LRT) involvement. Despite the ubiquity of URT infection, little is known about the relative cytopathogenesis of RSV infection in infant URT and LRT.

Extracting quantum work statistics and fluctuation theorems by single-qubit interferometry.

We propose an experimental scheme to verify the quantum nonequilibrium fluctuation relations using current technology. Specifically, we show that the characteristic function of the work distribution for a nonequilibrium quench of a general quantum system can be extracted by Ramsey interferometry of a single probe qubit. Our scheme paves the way for the full characterization of nonequilibrium processes in a variety of quantum systems, ranging from single particles to many-body atomic systems and spin chains.

Nonadherence in difficult asthma - facts, myths, and a time to act.

Nonadherence to prescribed treatment is an important cause of difficult asthma. Rates of nonadherence amongst asthmatic patients have been shown to range between 30% and 70%. This is associated with poor health care outcomes and increased health care costs.

Chronic IL9 and IL-13 exposure leads to an altered differentiation of ciliated cells in a well-differentiated paediatric bronchial epithelial cell model.

Asthma is a chronic inflammatory disease characterised by airways remodelling. In mouse models IL-9 and IL-13 have been implicated in airways remodelling including mucus hypersecretion and goblet cell hyperplasia. Their role, especially that of IL-9, has been much less studied in authentic human ex vivo models of the bronchial epithelium from normal and asthmatic children.

Can certain genotypes predispose to poor asthma control in children? A pharmacogenetic study of 9 candidate genes in children with difficult asthma.

Objective: We tested the hypothesis that patients with difficult asthma have an increased frequency of certain genotypes that predispose them to asthma exacerbations and poor asthma control.

Methods: A total of 180 Caucasian children with confirmed asthma diagnosis were selected from two phenotypic groups; difficult (n = 112) versus mild/moderate asthma (n = 68) groups. All patients were screened for 19 polymorphisms in 9 candidate genes to evaluate their association with difficult asthma.

Clinical outcomes and inflammatory biomarkers in current smokers and exsmokers with severe asthma.

Background: Clinical outcomes are worse in current smokers and exsmokers with mild-to-moderate asthma compared with never smokers, but little is known about the influence of smoking status in patients with severe asthma.

Objectives: We sought to examine the association of current or previous cigarette smoking with clinical and inflammatory variables in patients with severe asthma.

Methods: We compared patients' demographics, disease characteristics, and biomarkers of inflammation in current smokers (n=69 [9%]), exsmokers (n=210 [28%]), and never smokers (n=461 [62%]) with severe asthma (n=760) recruited to the British Thoracic Society Severe Asthma Registry.

Obesity-associated severe asthma represents a distinct clinical phenotype: analysis of the British Thoracic Society Difficult Asthma Registry Patient cohort according to BMI.

Background: Obesity has emerged as a risk factor for the development of asthma and it may also influence asthma control and airway inflammation. However, the role of obesity in severe asthma remains unclear. Thus, our objective was to explore the association between obesity (defied by BMI) and severe asthma.

Effects of quantum coherence in metalloprotein electron transfer.

Many intramolecular electron transfer (ET) reactions in biology are mediated by metal centers in proteins. This process is commonly described by a model of diffusive hopping according to the semiclassical theories of Marcus and Hopfield. However, recent studies have raised the possibility that nontrivial quantum mechanical effects play a functioning role in certain biomolecular processes.

The utility of fractional exhaled nitric oxide suppression in the identification of nonadherence in difficult asthma.

Rationale: Nonadherence to inhaled corticosteroid therapy (ICS) is a major contributor to poor control in difficult asthma, yet it is challenging to ascertain.

Objectives: Identify a test for nonadherence using fractional exhaled nitric oxide (Fe(NO)) suppression after directly observed inhaled corticosteroid (DOICS) treatment.

Methods: Difficult asthma patients with an elevated Fe(NO) (>45 ppb) were recruited as adherent (ICS prescription filling >80%) or nonadherent (filling <50%).

Single-locus species delimitation: a test of the mixed Yule-coalescent model, with an empirical application to Philippine round-leaf bats.

Prospects for a comprehensive inventory of global biodiversity would be greatly improved by automating methods of species delimitation. The general mixed Yule-coalescent (GMYC) was recently proposed as a potential means of increasing the rate of biodiversity exploration. We tested this method with simulated data and applied it to a group of poorly known bats (Hipposideros) from the Philippines.

Clinical management and outcome of refractory asthma in the UK from the British Thoracic Society Difficult Asthma Registry.

Refractory asthma represents a significant unmet clinical need. Data from a national online registry audited clinical outcome in 349 adults with refractory asthma from four UK specialist centres in the British Thoracic Society Difficult Asthma Network. At follow-up, lung function improved, with a reduction in important healthcare outcomes, specifically hospital admission, unscheduled healthcare visits and rescue courses of oral steroids.