Airway smooth muscle tone is influenced by many neurotransmitters, inflammatory mediators and drugs which interact direct or indirectly with specific surface receptors on smooth muscle cells. There have recently been important advances in our understanding of receptor mechanisms which may be relevant to understanding altered receptor function in airway inflammatory diseases. Neural control of airway tone is complex and several transmitters may be involved, including adrenoceptors, muscarinic receptors and receptors for various neuropeptides. Several inflammatory mediators, acting via specific receptors, may also influence airway smooth muscle. In the future molecular techniques which give information about the factors influencing receptor synthesis and post-translation processing will also provide further insights into understanding receptor function in airway disease.
Asthma is one of the commonest chronic diseases worldwide and is effectively controlled in most patients with maintenance treatment. In those with moderate or severe persistent asthma, control may be achieved with an inhaled corticosteroid or a combination inhaler containing a corticosteroid and a long acting β2 agonist. The combination inhaler is more effective, but patients still require short acting β2 agonists such as salbutamol or terbutaline to relieve symptoms. I describe a new approach for acute exacerbation—SMART (single inhaler maintenance and reliever therapy). This uses the combination inhaler, rather than the short acting β2 agonist, as the reliever. Using a formulation of budesonide plus formoterol (budesonide/formoterol) both as a reliever and as maintenance therapy once or twice daily is more effective in controlling asthma than conventional approaches using budesonide/formoterol, fluticasone/salmeterol, or high dose corticosteroids (budesonide or fluticasone) as the maintenance treatment with short acting β2 agonists as relievers (table⇓).1 2 3 4 5 The most striking benefits are fewer exacerbations (severe exacerbations, defined as needing a course of oral corticosteroids, are …
Prestressed stayed columns offer an innovative and aesthetically attractive solution where designs demand long and slender elements under compression. The addition of cross-arms and pretensioned cables to the columns provides significant lateral and rotational support that can result in a marked increase of the buckling capacity. The current work presents a simplified model, comprising discrete rigid links and springs with a mathematically exact formulation including the destabilising effect of cable slackening, which mimics the response of stayed columns and reveals the governing physical parameters that drive the behaviour. A recent finite-element study had indicated that these structural components are likely to exhibit interactive buckling phenomena, particularly if the critical buckling mode is antisymmetric, leading to highly unstable responses. However, by its very nature, that study could not reveal the bifurcational structure of the equilibrium response. The results from the present model reveal similar behaviour to that observed in the earlier finite-element study. A sequence of bifurcations is found that switch the post-buckling response from one mode to another by way of a path of interactive buckling.
The effect of element interaction and material nonlinearity on the ultimate capacity of stainless steel plated cross-sections is investigated in this paper. The focus of the research lies in cross-sections failing by local buckling; member instabilities, distortional buckling and interactions thereof with local buckling are not considered. The cross-sections investigated include rectangular hollow sections (RHS), I sections and parallel flange channels (PFC). Based on previous finite element investigations of structural stainless steel stub columns, parametric studies were conducted and the ultimate capacity of the aforementioned cross-sections with a range of element slendernesses and aspect ratios has been obtained. Various design methods, including the effective width approach, the direct strength method (DSM), the continuous strength method (CSM) and a design method based on regression analysis, which accounts for element interaction, were assessed on the basis of the numerical results, and the relative merits and weaknesses of each design approach have been highlighted. Element interaction has been shown to be significant for slender cross-sections, whilst the behaviour of stocky cross-sections is more strongly influenced by the material strain-hardening characteristics. A modification to the continuous strength method has been proposed to allow for the effect of element interaction, which leads to more reliable ultimate capacity predictions. Comparisons with available test data have also been made to demonstrate the enhanced accuracy of the proposed method and its suitability for the treatment of local buckling in stainless steel cross-sections.
Chronic obstructive pulmonary disease (COPD) is a heterogeneous syndrome and may comprise several different phenotypes that are driven by different molecular mechanisms (endotypes). Several different clinical, genetic, and inflammatory phenotypes of COPD have been recognized and this may lead to more precise effective therapies.The different clinical phenotypes, including smoking versus nonsmoking COPD, small airway disease versus emphysema, non-exacerbators versus frequent exacerbators are discussed. Rare genetic endotypes (alpha1-antitrypsin deficiency, telomerase polymorphisms), and inflammatory phenotypes (eosinophilic versus neutrophilic) are also recognized in stable and exacerbating patients and have implications for the choice of therapy.Clinical phenotypes have so far not proved to be very useful in selecting more personalized therapy for COPD. Even with genetic endotypes, this has not led to improved therapy. More promising is the recognition that COPD patients who have increased sputum or blood eosinophils tend to have more frequent exacerbations and inhaled corticosteroids are more effective in preventing exacerbation. Increased blood eosinophils have proved to be a useful biomarker now used to target ICS more effectively. Furthermore, COPD patients with low eosinophils are more likely to get pneumonia with ICS and to have lower airway bacterial colonization.
We present SOFIA+ALMA continuum and spectral-line polarisation data on the massive molecular cloud BYF 73, revealing important details about the magnetic field morphology, gas structures, and energetics in this unusual massive star formation laboratory. The 154$μ$m HAWC+ polarisation map finds a highly organised magnetic field in the densest, inner 0.55$\times$0.40 pc portion of the cloud, compared to an unremarkable morphology in the cloud's outer layers. The 3mm continuum ALMA polarisation data reveal several more structures in the inner domain, including a pc-long, $\sim$500 M$_{\odot}$ "Streamer" around the central massive protostellar object MIR 2, with magnetic fields mostly parallel to the east-west Streamer but oriented north-south across MIR 2. The magnetic field orientation changes from mostly parallel to the column density structures to mostly perpendicular, at thresholds $N_{\rm crit}$ = 6.6$\times$10$^{26}$ m$^{-2}$, $n_{\rm crit}$ = 2.5$\times$10$^{11}$ m$^{-3}$, and $B_{\rm crit}$ = 42$\pm$7 nT. ALMA also mapped Goldreich-Kylafis polarisation in $^{12}$CO across the cloud, which traces in both total intensity and polarised flux, a powerful bipolar outflow from MIR 2 that interacts strongly with the Streamer. The magnetic field is also strongly aligned along the outflow direction; energetically, it may dominate the outflow near MIR 2, comprising rare evidence for a magnetocentrifugal origin to such outflows. A portion of the Streamer may be in Keplerian rotation around MIR 2, implying a gravitating mass 1350$\pm$50 M$_{\odot}$ for the protostar+disk+envelope; alternatively, these kinematics can be explained by gas in free fall towards a 950$\pm$35 M$_{\odot}$ object. The high accretion rate onto MIR 2 apparently occurs through the Streamer/disk, and could account for $\sim$33% of MIR 2's total luminosity via gravitational energy release.
