Mechanical Testing of Extruded Magnesium for the Development of Automobile Seat Frame Structures

To validate a novel structural concept in magnesium lightweighting in early development stages, a magnesium alloy of type MgMnCe is characterized at coupon level and validated at profile level. The feasibility of friction stir welding is confirmed to integrate the alloy into the structure. Specimens are extracted from or set up on basis of generic profiles. For characterization amongst others, miniature tensile specimens in extrusion and transverse direction are utilized. Tensile results show the orthotropic material character of the ME21 alloy used. In transverse direction stiffness as well as strength increases, while elongation at break decreases. The material shows a strongly nonlinear, irreversible material behavior starting at small loads and a moderate strain-rate dependency. On profile level, closed rectangular profiles in four-point bending are used for validation at high impact velocities. These tests reveal large deformation without local failure. This deformation makes the use of closed rectangular profiles promising for the application in seat backrest structures

Pulmonary therapy podcast-COVID-19: Research and real-world experiences from the Editorial Board

The Editorial Board have prepared a podcast describing their experiences over the past year of the COVID-19 pandemic. The Editorial Board describe how COVID-19 impacted their research and how the initial clinical response changed over the course of the year in terms of treatment, personal protective equipment (PPE), and policy changes. The podcast and transcript can be viewed below the abstract of the online version of the manuscript. Alternatively, the podcast and transcript can be downloaded here: https://doi.org/10.6084/m9.figshare.1440229

Relationship between FEV1 change and patient-reported outcomes in randomised trials of inhaled bronchodilators for stable COPD: a systematic review.

BACKGROUND: Interactions between spirometry and patient-reported outcomes in COPD are not well understood. This systematic review and study-level analysis investigated the relationship between changes in FEV1 and changes in health status with bronchodilator therapy. METHODS: Six databases (to October 2009) were searched to identify studies with long-acting bronchodilator therapy reporting FEV1 and health status, dyspnoea or exacerbations. Mean and standard deviations of treatment effects were extracted for each arm of each study. Relationships between changes in trough FEV1 and outcomes were assessed using correlations and random-effects regression modelling. The primary outcome was St George's Respiratory Questionnaire (SGRQ) total score. RESULTS: Thirty-six studies (≥ 3 months) were included. Twenty-two studies (23,654 patients) with 49 treatment arms each contributing one data point provided SGRQ data. Change in trough FEV1 and change in SGRQ total score were negatively correlated (r = -0.46, p < 0.001); greater increases in FEV1 were associated with greater reductions (improvements) in SGRQ. The correlation strengthened with increasing study duration from 3 to 12 months. Regression modelling indicated that 100 mL increase in FEV1 (change at which patients are more likely to report improvement) was associated with a statistically significant reduction in SGRQ of 2.5 (95% CI 1.9, 3.1), while a clinically relevant SGRQ change (4.0) was associated with 160.6 (95% CI 129.0, 211.6) mL increase in FEV1. The association between change in FEV1 and other patient-reported outcomes was generally weak. CONCLUSIONS: Our analyses indicate, at a study level, that improvement in mean trough FEV1 is associated with proportional improvements in health status

Patient-reported barriers to accepting a technological adherence package in the MAGNIFY trial.

Peer reviewedPostprin

Long-acting bronchodilators improve exercise capacity in COPD patients : a systematic review and meta-analysis

Background: We carried out a systematic review and meta-analysis with the aim to evaluate the efficacy of long-acting bronchodilators on exercise capacity in COPD patients. Methods: The endpoints were the efficacy of long-acting bronchodilators (altogether, and by single classes) vs. placebo in modifying endurance time (ET), inspiratory capacity (IC) and dyspnea during exercise, taking into consideration the outcomes according to different patients' inclusion criteria and exercise methodology. Results: Twenty-two studies were deemed eligible for analysis. Weighted mean increase in ET resulted of 67 s (95% CI ranges from 55 to 79). For isotime IC and dyspnea during exercise, weighted improvements were 195 ml (162-229), and - 0.41 units (- 0.56 to - 0.27), respectively. The increase in trough IC was 157 ml (138-175). We found a trend in favour of LAMA compared to LABA in terms of ET. In the 11 studies which reported a value of functional residual capacity > 120% as inclusion criterion, weighted mean increase in endurance time was 94 s (65 to 123); however we did not find any significant correlation between ET and mean trough IC (P: 0.593). The improvement of ET in the 5 studies using walking as exercise methodology resulted of 58 s (- 4 to 121). Conclusions: Long-acting bronchodilators improve exercise capacity in COPD. The main effect of long-acting bronchodilators seems to be a decrease of basal IC rather than a modification of dynamic hyperinflation during exercise. The efficacy in terms of endurance time seems higher in studies which enrolled patients with hyperinflation, with a similar efficacy on walking or cycling

Long-term benefits of omalizumab in a patient with severe non-allergic asthma

<p>Abstract</p> <p>Introduction</p> <p>Currently, omalizumab is indicated for the treatment of patients with severe allergic uncontrolled asthma despite optimal therapy.</p> <p>Case presentation</p> <p>We studied a 52-year-old man who has been suffering from severe non allergic steroid-resistant asthma with increased levels of total IgE and a lot of comorbidity. After a 3 years long treatment with omalizumab, he presented a significant improvement in disease control in terms of hospitalizations, exacerbation, quality of life and lung function with good safety profile.</p> <p>Conclusion</p> <p>Our case shows, after a long follow-up, how omalizumab can be effective in a severe form of non-atopic asthma. It is therefore hoped that further studies can identify indicators that are able to give to clinicians information about patients who can be responsive to monoclonal anti-IgE antibody even if non allergic.</p

Role of aberrant metalloproteinase activity in the pro-inflammatory phenotype of bronchial epithelium in COPD

<p>Abstract</p> <p>Background</p> <p>Cigarette smoke, the major risk factor for COPD, is known to activate matrix metalloproteinases in airway epithelium. We investigated whether metalloproteinases, particularly A Disintegrin and Metalloproteinase (ADAM)17, contribute to increased pro-inflammatory epithelial responses with respect to the release of IL-8 and TGF-α, cytokines implicated in COPD pathogenesis.</p> <p>Methods</p> <p>We studied the effects of cigarette smoke extract (CSE) and metalloproteinase inhibitors on TGF-α and IL-8 release in primary bronchial epithelial cells (PBECs) from COPD patients, healthy smokers and non-smokers.</p> <p>Results</p> <p>We observed that TGF-α was mainly shed by ADAM17 in PBECs from all groups. Interestingly, IL-8 production occurred independently from ADAM17 and TGF-α shedding, but was significantly inhibited by broad-spectrum metalloproteinase inhibitor TAPI-2. CSE did not induce ADAM17-dependent TGF-α shedding, while it slightly augmented the production of IL-8. This was accompanied by reduced endogenous inhibitor of metalloproteinase (TIMP)-3 levels, suggesting that CSE does not directly but rather indirectly alter activity of ADAM17 through the regulation of its endogenous inhibitor. Furthermore, whereas baseline TGF-α shedding was lower in COPD PBECs, the early release of IL-8 (likely due to its shedding) was higher in PBECs from COPD than healthy smokers. Importantly, this was accompanied by lower TIMP-2 levels in COPD PBECs, while baseline TIMP-3 levels were similar between groups.</p> <p>Conclusions</p> <p>Our data indicate that IL-8 secretion is regulated independently from ADAM17 activity and TGF-α shedding and that particularly its early release is differentially regulated in PBECs from COPD and healthy smokers. Since TIMP-2-sensitive metalloproteinases could potentially contribute to IL-8 release, these may be interesting targets to further investigate novel therapeutic strategies in COPD.</p