Health professionals tasked with advising patients with asthma and chronic obstructive pulmonary disease (COPD) how to use inhaler devices properly and what to do about unwanted effects will be aware of a variety of commonly held precepts. The evidence for many of these is, however, lacking or old and therefore in need of re-examination. Few would disagree that facilitating and encouraging regular and proper use of inhaler devices for the treatment of asthma and COPD is critical for successful outcomes. It seems logical that the abandonment of unnecessary or ill-founded practices forms an integral part of this process: the use of inhalers is bewildering enough, particularly with regular introduction of new drugs, devices and ancillary equipment, without unnecessary and pointless adages. We review the evidence, or lack thereof, underlying ten items of inhaler 'lore' commonly passed on by health professionals to each other and thence to patients. The exercise is intended as a pragmatic, evidence-informed review by a group of clinicians with appropriate experience. It is not intended to be an exhaustive review of the literature; rather, we aim to stimulate debate, and to encourage researchers to challenge some of these ideas and to provide new, updated evidence on which to base relevant, meaningful advice in the future. The discussion on each item is followed by a formal, expert opinion by members of the ADMIT Working Group.
Molecular biology: principles and applications Analysis of protein synthesis Methods for in situ hybridization Finding disease genes Protein and gene polymorphisms Site directed mutagenesis Tissue specificity Applications of molecular biology to lung disease: bacterial infection Molecular biology and respiratory disease Application to pathology Oncogenes, cancer and growth factors Molecular biology of lung receptors The regulation of collagen and elastin gene expression in normal lung and during pulmonary disease Transepithelial transport of secretory immunoglobulins Heat shock proteins Molecular cellular and genetic studies of atopic disease Interleukins in the pulmonary inflammatory response Gene therapy
We used FIR and submillimeter continuum data from Herschel and the Atacama Pathfinder EXperiment (APEX) to fit pixel-by-pixel modified Planck SEDs to prestellar and protostellar clumps in the Census of High- and Medium-mass Protostars (CHaMP) ($280^{\circ}<\ell<300^{\circ}$, $-4^{\circ}<b<+2^{\circ}$). We present maps of dust temperature ($T_{\text{d}}$) and H$_2$ column density (\ncol) for molecular clumps in the Carina Nebula complex (Regions 9 through 11), and surrounding RCW 64 (Region 26). We compare the column densities of CO and H$_2$ to chart regional variations in their correspondence, and derive maps of the CO abundance. We find the CO abundance varies by an order of magnitude or more across each region, averaging a few$\times$10$^{-5}$ CO per H$_2$, and that the CO abundance distribution across each clump is correlated in both form and magnitude with environmental conditions, especially $T_{\text{d}}$. This demonstrates that no single CO abundance suffices to convert from $N_{\text{CO}}$ to \ncol, even within a single molecular cloud. We also find that $L/M$ traces $T_{\text{d}}$ almost exclusively, and therefore is not an independent star formation tracer, but minima in $T_{\text{d}}$ almost universally coincide with maxima in \ncol, implying that cooling and density enhancement must be simultaneous steps in prestellar clump evolution. Finally, based on generalized histogram N-PDFs of clump-scale (1-5 pc) and cloud-scale ($\gtrsim10$ pc) samples, we could only obtain dual log-normal and power-law fits to $\sim10\%$ of the clumps. The physical parameters derived from these fits approach theoretical expectations, but have largely unknown uncertainties, so we advise treating the results of N-PDF fitting with caution.
Advanced structural analysis is commonly carried out using finite element models constructed using beam elements. Beam elements are incapable of capturing the effects of local buckling. However, disregarding local buckling can lead to overestimations of system strengths leading to unsafe design. In traditional design approaches, time-consuming semi-empirical design calculations are carried out on individual members. However, with improvements in computational power and advances in software, system-level advanced analysis is now viable for widespread use in design. A proposal is made herein, in which strain limits, defined by the Continuous Strength Method, are applied to simulate local buckling in beam element models, thereby controlling the extent to which spread of plasticity, moment redistribution and strain hardening can be exploited. Strains are averaged over a finite length of member to reflect the fact that local buckling requires a finite length over which to develop and to allow for local moment gradient effects. The paper includes a numerical assessment of the proposed method for design at member level, with both I-sections and hollow sections considered. Comparisons against current design methods confirm the significant benefits of the proposed approach. Application of the approach is particularly appropriate for stainless steel structures due to the high material value and the complexities presented by the nonlinear material stress-strain response for traditional design treatments.
Although endothelial cell (EC)-dependent relaxation has been described in most mammals, there have been no detailed reports of its existence in humans. Consequently, we evaluated human pulmonary artery segments taken from uninvolved regions of resected lung from 11 patients. EC removal did not significantly alter relaxation to vasoactive intestinal peptide (VIP). However, relaxation to acetylcholine (ACh) was observed only in segments with EC. Preincubation with either 1 microM propranolol or 10 microM indomethacin failed to block relaxation, but the addition of either 30 microM quinacrine hydrochloride or 100 microM nordihydroguaiaretic acid prevented it entirely. EC-dependent relaxation to ATP was also demonstrated. These data demonstrate that EC-dependent relaxation occurs in human pulmonary arteries. Neither beta-adrenergic pathways nor prostaglandin intermediaries are utilized. An oxidized breakdown product of arachidonic or some other fatty acid from EC phospholipid appears to be involved. These data suggest that interactions between endothelium and smooth muscle may be important in modulating tone in the vessel wall and that damage to the endothelium may play a role in the development of pulmonary hypertension in humans.
Restenosis remains the major limitation of coronary catheter-based intervention. In small vessels, the amount of neointimal tissue is disproportionately greater than the vessel caliber, resulting in higher restenosis rates. In the Randomized Study With the Sirolimus-Eluting Bx Velocity Balloon-Expandable Stent (RAVEL) trial, approximately 40% of the vessels were small (<2.5 mm). The present study evaluates the relationship between angiographic outcome and vessel diameter for sirolimus-eluting stents.Patients were randomized to receive either an 18-mm bare metal Bx VELOCITY (BS group, n=118), or a sirolimus-eluting Bx VELOCITY stent (SES group, n=120). Subgroups were stratified into tertiles according to their reference diameter (RD; stratum I, RD <2.36 mm; stratum II, RD 2.36 mm to 2.84 mm; stratum III, RD >2.84 mm). At 6-month follow-up, the restenosis rate in the SES group was 0% in all strata (versus 35%, 26%, and 20%, respectively, in the BS group). In-stent late loss was 0.01+/-0.25 versus 0.80+/-0.43 mm in stratum I, 0.01+/-0.38 versus 0.88+/-0.57 mm in stratum II, and -0.06+/-0.35 versus 0.74+/-0.57 mm in stratum III (SES versus BS). In SES, the minimal lumen diameter (MLD) remained unchanged (Delta -0.72 to 0.72 mm) in 97% of the lesions and increased (=late gain, DeltaMLD <-0.72 mm) in 3% of the lesions. Multivariate predictors for late loss were treatment allocation (P<0.001) and postprocedural MLD (P= 0.008).Sirolimus-eluting stents prevent neointimal proliferation and late lumen loss irrespective of the vessel diameter. The classic inverse relationship between vessel diameter and restenosis rate was seen in the bare stent group but not in the sirolimus-eluting stent group.
