No abstract is provided for this article.
Painful radiotherapeutic procedures on lower limbs are susceptible to spinal anaesthesia. This method is shown to be suitable in children when neuroleptanalgesia provides amnesia, an adequate period of patient immobility, and stable cardiovascular and respiratory conditions. The technique is useful in overcoming the problems of anaesthesia in the radiotherapy environment.
The stability and design of stainless steel equal-leg angle section members subjected to uniaxial bending are studied herein. An experimental investigation, comprising material testing, initial geometric imperfection measurements and physical tests on hot-rolled austenitic stainless steel equal-leg angle section beams is first presented. The test results are then used to validate shell finite element models developed within ABAQUS, which are in turn used to undertake numerical parametric studies that consider both hot-rolled and cold-formed equal-leg angle section beams in austenitic, duplex and ferritic stainless steel with a wide range of slenderness values. Recent studies have shown that for angles under major-axis bending, both lateral-torsional and local buckling can arise, while under minor-axis bending, lateral-torsional buckling and Brazier-type flattening can occur. When designing for major-axis bending according to Eurocode 3, both local and lateral-torsional buckling are considered; it is shown herein that equal-leg angle sections under major-axis bending can be designed using a normalised slenderness based on the minimum of the local and lateral-torsional elastic buckling moments, while also considering their ratio. Under minor-axis bending, however, in comparison with the current provisions in Eurocode 3 that only require cross-section checks, it is shown that both safer and more accurate resistance predictions can be achieved when account is taken for lateral-torsional buckling and Brazier-type flattening. New design proposals for stainless steel equal-leg angle section beams, covering both major- and minor-axis bending, are therefore developed. The proposed design rules offer substantially more accurate and consistent resistance predictions compared to existing codified design rules. The reliability of the new design provisions, with a recommended partial safety factor γM1=1.1, is verified following the procedure provided in EN 1990.
No abstract is provided for this article.
<h3>Introduction</h3> Bacteria are associated with COPD exacerbations with <i>Haemophilus influenzae</i>, and <i>Streptococcus pneumoniae</i> being predominant. Airway epithelium can protect pathogens from host defences and antibiotic treatment by internalisation. The mechanisms of this are unclear but may involve phosphoinositide-3- kinase (PI3K), p38, and ERK pathways. This requires many primary cells and therefore a validated cell line model would be of benefit. Therefore, we compared uptake of pathogenic bacteria by airway epithelial cells from non-smokers and COPD patients with A549 and BEAS-2B cell lines and the effects of pathway inhibitors were examined. <h3>Methods</h3> Non-smoker (n=7) and COPD (n=8) primary airway epithelial cells, and cell lines (BEAS-2B and A549 n=5) were incubated with fluorescently-labelled, heat-killed, <i>H. influenzae</i>, <i>S. pneumoniae</i>, or <i>E. coli</i> for up to 72 hours and uptake fluorimetrically. Confocal microscopy was used to confirm internalisation of bacteria. CXCL8 release was measured using ELISA. Effects of pathway inhibitors were determined by pre-treating cells with increasing concentrations of LY294002 (PI3K inhibitor), VX745 (p38 inhibitor), or PD98059 (ERK pathway inhibitor). Cell viability was assessed by MTT assay. <h3>Results</h3> Primary airway epithelial cells internalised respiratory bacteria <i>spp.</i> but not <i>E. coli</i>, in a time-dependent manner, with COPD cells internalising more <i>H. influenzae</i> but not <i>S. pneumoniae</i> compared to non-smokers at 48 hour (<i>H. influenzae</i> Non-smoker: 0.97±0.23 <i>vs</i>. COPD: 2.49±0.7 RFU χ 10<sup>3</sup>, p<0.05) and 72 hour (<i>H. influenzae</i> Non-smoker: 1.44±0.35 <i>vs</i>. COPD: 3.01±2.2 RFU χ 10<sup>3</sup>, p<0.05). A549 cells engulfed more bacteria than primary cells but the responses of BEAS-2B cells were similar to COPD cells and were used for subsequent experiments. Uptake was inhibited by LY294002 and PD98059, but not VX745. Conversely VX745, but not LY294002 or PD98059 inhibited CXCL8 release (Table 1). None of the treatments affected cell viability. <h3>Conclusion</h3> COPD airway epithelial cells engulf more <i>H. influenzae</i> than cells from non-smokers and this can be modelled by BEAS-2B cells. Uptake appears to require PI3K and ERK pathways but not p38 although, p38 is required for cytokine release. These data suggest that PI3K or MEK inhibitors in combination with antibiotics might be a good therapeutic strategy to treat bacterial exacerbations and recolonisation in COPD.
Extract: Asthma has now become one of the most common chronic diseases in industrialized countries and is predicted to increase throughout the world over the next decade, particularly in developing countries. Previously, asthma was viewed as a disease of bronchoconstriction (closing of the airways) and treated predominantly with bronchodilators (drugs which open up the airways), but more recently it has been seen as an inflammatory disease of the airways and the mainstay of modern management is treatment with inhaled corticosteroids. The airway inflammation in asthma is characterized by activation of mast cells, infiltration of eosinophils and increased activated T helper 2 (Th2) lymphocytes. Inhaled corticosteroids have revolutionized the management of asthma, leading to better control of asthma, reduced hospital admissions and a reduced mortality. Corticosteroids and long-acting beta2-agonists (salmeterol and formoterol) in fixed combination inhalers are currently the most effective therapy for asthma and are increasingly used in all patients with persistent symptoms.
