We report the second complete molecular line data release from the {\em Census of High- and Medium-mass Protostars} (CHaMP), a large-scale, unbiased, uniform mapping survey at sub-parsec resolution, of mm-wave line emission from 303 massive, dense molecular clumps in the Milky Way. This release is for all $^{12}$CO $J$=1$\rightarrow$0 emission associated with the dense gas, the first from Phase II of the survey, which includes $^{12}$CO, $^{13}$CO, and C$^{18}$O. The observed clump emission traced by both $^{12}$CO and HCO$^+$ (from Phase I) shows very similar morphology, indicating that, for dense molecular clouds and complexes of all sizes, parsec-scale clumps contain $\Xi$ ~ 75% of the mass, while only 25% of the mass lies in extended (>~ 10 pc) or "low density" components in these same areas. The mass fraction of all gas above a density 10$^9$ m$^{-3}$ is $\xi_9$ >~ 50%. This suggests that parsec-scale clumps may be the basic building blocks of the molecular ISM, rather than the standard GMC concept. Using $^{12}$CO emission, we derive physical properties of these clumps in their entirety, and compare them to properties from HCO$^+$, tracing their denser interiors. We compare the standard X-factor converting $I_{CO}$ to $N_{H_2}$ with alternative conversions, and show that only the latter give whole-clump properties that are physically consistent with those of their interiors. We infer that the clump population is systematically closer to virial equilibrium than when considering only their interiors, with perhaps half being long-lived (10s of Myr), pressure-confined entities which only terminally engage in vigorous massive star formation, supporting other evidence along these lines previously published.
Reinstatement in the light of new evidence? Theophylline has been used as a bronchodilator in the treatment of COPD for over 70 years, but has lost popularity as better tolerated and more effective bronchodilators have been introduced. However, new insights into the molecular action of theophylline have raised the possibility that this old drug may come back into favour as an anti-inflammatory treatment and may even reverse steroid resistance in COPD.1 A paper by Hirano et al in this issue of Thorax provides further support for the anti-inflammatory effects of theophylline in patients with COPD.2 In the major guidelines for the treatment of COPD, theophylline is relegated to a third line bronchodilator after inhaled anticholinergics and β2 agonists. Nevertheless, it is recognised that theophylline is a useful treatment in patients with severe COPD as its withdrawal leads to significant clinical worsening of the disease.3 Many older clinicians have been convinced by its clinical value in severe disease. Traditionally, theophylline was used as a bronchodilator in the treatment of airway disease but, to achieve significant bronchodilatation comparable with that of a β2 agonist, relatively high plasma concentrations are needed (10–20 mg/l). Theophylline relaxes human airway smooth muscle in vitro through inhibition of phosphodiesterases (PDE), enzymes that break down cyclic nucleotides in the …
We investigated the distribution of adrenergic receptors in ferret trachea using autoradiography. [3H]Dihydroalprenolol, used to identify beta–-adrenoceptors, revealed a high density of specific binding sites over surface epithelium and submucosal glands, with less labelling of smooth muscle. [3H] prazosin labelling showed that alpha 1-receptors were numerous in glands and epithelium, but sparse in smooth muscle. Comparison of adrenergic receptor densities in tracheal sections from the same animals showed a rank order for submucosal glands of alpha l > beta, for epithelium beta > alphai and for smooth muscle beta > alpha1. Within the submucosal glands, alpha1 and beta-adrenergic receptors were differentially distributed, with alpha1 receptors being significantly more numerous over serous than mucous cells and beta receptors being significantly more numerous over mucous than serous cells. This technique provides insight into adrenergic regulation of airway function and should be useful in investigations of how relative receptor densities may be altered in disease.
Abstract The Continuous Strength Method (CSM) provides accurate cross‐section resistance predictions since allowance is made for the partial spread of plasticity and the beneficial effects of strain hardening. Although CSM design provisions for different loading conditions are available, the method was limited to the determination of cross‐sectional resistance until recent research by Arrayago et al. (2020) proposed a consistent new approach to the design of stainless steel hollow section members subjected to compression. Extension of the CSM to the design of stainless steel members subjected to combined compression and bending moment is presented in this paper. The analysis is based on numerical results generated in the current study and existing results collected from the literature on stainless steel hollow section members. The results demonstrate that the adoption of the CSM design equations to predict column strength considerably improves the accuracy of the calculated beam‐column capacities. The reliability of the proposed approach is demonstrated through statistical analyses performed in accordance with EN 1990.
The term "brittle asthma" was first used in 1977 to describe patients with asthma who maintained a wide variation in peak expiratory flow (PEF) despite high doses of inhaled steroids. 1It was coined at a time when patterns of PEF variability were beginning to be described with respect to clinical patterns of disease, such as the morning dip in PEF 1 2 and the "double dip" pattern of morning and evening dips 3 seen in patients with less well controlled asthma.The brittle asthmatic PEF pattern of variability was identified as a separate group, being described as chaotic showing no such obvious repeating pattern.The significance of the brittle pattern was not completely clear at that time, although the inference was that these patients had more severe asthma that was, by definition, more difficult to control.Three papers published shortly afterwards showed that this chaotic pattern of PEF could lead to death from an acute severe attack 4-6 and the authors raised the possibility that these patients tended to be poorly compliant with treatment.Nevertheless, not all non-compliant patients showed this chaotic pattern, so clearly other factors were important.However, it is not clear how these patients would fit into a classification of severe asthma which would include all those patients at risk of death or repeated hospital admissions.Some physicians are unhappy with brittle asthma being classified as a separate asthma phenotype, regarding these patients as simply the severe end of the spectrum.However, it is our belief that definition of diVering asthma phenotypes is important, so what follows represents our view that brittle asthma should be considered as a specific asthma phenotype.We suggest how further study of patients of this type may help in unravelling the pathogenesis and treatment of at risk asthma.
In some parts of the world in recent years there has been an increase in morbidity of asthma and in deaths from the disease. The subject is a very complex one and carefully designed and conducted studies are needed to clarify the situation.
1. Opioid receptors have been localised on sensory fibres in the vagus nerve and opioids have previously been shown to inhibit non-adrenergic, non-cholinergic (NANC) neurotransmission in guinea-pig bronchi in vitro and in vivo. We have now investigated whether an inhibitory effect could be demonstrated on cholinergic neurotransmission. 2. Electrical field stimulation (EFS) (8 Hz, 0.5 ms, 40 V for 20 s) produced only a rapid, cholinergic response in the upper trachea but in the lower trachea and main bronchi a cholinergic response which was atropine-sensitive and a longer lasting NANC contraction that was atropine-insensitive was demonstrated. This slow contraction could be blocked by tetrodotoxin and capsaicin pretreatment. 3. [D-Ala2, NMePhe4, Gly-ol5]enkephalin (DAMGO), a selective mu-opioid receptor agonist, inhibited the cholinergic response to EFS at 8 Hz in a dose-dependent manner in main bronchi (IC50 = 113 nM with a maximal inhibition of 35.7 +/- 5.6% 10 microM, n = 5). In the lower trachea, DAMGO inhibited the cholinergic response to a similar extent (inhibition of 35.8 +/- 3.5% at 10 microM, n = 5). However, DAMGO had no effect on the contractile response to exogenously applied acetylcholine in the main bronchi. By contrast, opioids had no inhibitory effect on cholinergic neurotransmission in the upper trachea. DAMGO (1 microM) inhibited the cholinergic response to EFS in a frequency-dependent manner in the main bronchi with greater inhibition at lower frequencies of stimulation. 4. The delta-opioid receptor agonist [D-Pen2, D-Pen5]enkephalin (DPDPE) significantly inhibited the cholinergic component of the constrictor response to EFS at 8 Hz in the bronchi but at the highest dose used (10 microM). U-50,488H, a Kappa-receptor agonist, had no inhibitory effect on the cholinergic constrictor component in the main bronchi (10microM). 5. DAMGO also inhibited the NANC responses to EFS in the main bronchi in a dose-dependent manner (with an IC50 = 36 nm and a maximal inhibition of 63.4 + 8.3%, at 1 microM, n = 5). DAMGO had no effect on contractile responses to exogenously applied substance P (SP). DPDPE (10 microM) was less effective in inhibition of the NANC bronchoconstriction with a maximal inhibition of 29.2 + 4.2% (n = 7), and U-50,488H (1O microM) had no inhibitory effect. 6. After capsaicin pretreatment, which depleted sensory nerves of neuropeptides, the inhibitory effect of DAMGO (1 microM) on cholinergic constriction in main bronchi at 8 Hz was only 13.4 + 1.9% (n = 13) compared with 32.9 + 4.0% (n = 9) inhibition in vehicle-treated controls (P < 0.001). 7. Opioids may reduce the cholinergic neural responses in airways partly via an inhibitory action on excitatory NANC nerves and partly by a direct effect on cholinergic neurotransmission. The opioid receptor involved is of the mu-opioid receptor subtype.
ABSTRACTThe number of people with asthma continues to grow around the world. However, despite the availability of highly effective medication it remains a poorly controlled disease. Reasons for this poor control include non-implementation and inherent limitations of the asthma management guidelines, poor compliance with asthma therapy, incorrect use of inhaler devices and insufficient treatment of peripheral airway inflammation. Guidelines may not be efficiently implemented as they may be complicated and difficult to understand. In addition, the scientific evidence upon which they are based, although the best available at the present time, is flawed. Patient non-compliance with therapy is a major reason for poor asthma control. Patients fail to comply with their asthma regimen for a wide variety of reasons, but incorrect use of inhaler devices is amongst the most common. Most patients derive incomplete benefit from pressurised metered dose inhalers (pMDIs) as they are unable to use them correctly. Dry powder inhalers (DPIs) have several advantages over pMDIs; they are breath-activated (avoiding coordination difficulties between actuation and inhalation), easy and convenient to use, and environmentally friendly. Although there are many treatments for asthma currently in development, it is unlikely that significant improvements in inhaled medication will occur within the next 15 years. Therefore, improvement in asthma management will be facilitated by improvements in inhaler technology. When choosing an inhaler device it is essential that it is easy to use correctly, dosing is consistent, adequate drug is deposited in the lungs (both central and peripheral airways) and that drug deposition is independent of airflow.Key words:: Asthma controlAsthma managementInhalation devicesNon-compliancePatient choice
To determine whether women have an unfavorable outcome after coronary interventions compared with men, we evaluated patients undergoing revascularisation within the Arterial Revascularisation Therapies Study (ARTS).We evaluated 1205 patients (23% women) with multivessel disease randomised to percutaneous or surgical coronary revascularisation. The in-hospital results, and clinical outcome at five years were evaluated. Women were older, with a higher prevalence of hypertension, hypercholesterolaemia, family history for coronary artery disease (all p<0.001), diabetes mellitus (p=0.05) and stable angina (p<0.05) than men, but had a lower incidence of history of myocardial infarction or smoking (both p<0.001). More major bleeding complications, even after adjusting for baseline clinical characteristics (OR 29.4, 95% CI: 5.3-500, p<0.005) were observed in women following percutaneous coronary intervention. During clinical follow-up freedom from major adverse cardiac and cerebrovascular events was similar in men and women, regardless of treatment strategy. Men assigned to bypass surgery had a better quality of life, but women reported more frequently angina.The clinical outcome of women with multivessel disease undergoing coronary revascularisation was similar to that in men. However, women presented more bleeding complications before hospital discharge, and had less favourable assessment in specific domain of daily life at follow-up.
