Additive layer techniques, such as laser sintering, are increasingly being considered for the production of fully functioning end-use parts due to the significant advantages they hold in the design ...and implementation of products. However, one of the main obstacles to widespread adoption of this technology is the limited range of materials that can currently be processed using additive techniques. This paper presents initial research into the reinforcement of laser sintered polyamides with carbon nanofibres (CNFs). The effects of CNF addition on the processing parameters and mechanical properties of laser sintered parts have been investigated. A 3wt % carbon nanofibre-polyamide 12 composite (CNF-PA12) powder was prepared using melt mixing and cryogenic milling. Following laser sintering, characterisation of the polymer nanocomposite parts by SEM and dynamic mechanical testing showed that the nanofibres were well dispersed within the polymer matrix and gave a 22% increase in the storage modulus compared to the base material. However, the cryogenic fracturing method used in this research did not produce powder with suitable morphology for laser sintering. If improved powder production can be achieved, the use of CNF reinforcements to improve mechanical properties in laser sintering holds promise.
There is limited data on the risk factors and phenotypical characteristics associated with spirometrically confirmed COPD in never-smokers in the general population.
To compare the characteristics ...associated with COPD by gender and by severity of airway obstruction in never-smokers and in ever-smokers.
We analysed the data from 5176 adults aged 40 years and older who participated in the initial cross-sectional phase of the population-based, prospective, multisite Canadian Cohort of Obstructive Lung Disease study. Never-smokers were defined as those with a lifetime exposure of <1/20 pack year. Logistic regressions were constructed to evaluate associations for 'mild' and 'moderate-severe' COPD defined by FEV1/FVC <5th centile (lower limits of normal). Analyses were performed using SAS V.9.1 (SAS Institute, Cary, North Carolina, USA).
The prevalence of COPD (FEV1/FVC<lower limits of normal) in never-smokers was 6.4%, constituting 27% of all COPD subjects. The common independent predictors of COPD in never-smokers and ever-smokers were older age, self reported asthma and lower education. In never-smokers a history of hospitalisation in childhood for respiratory illness was discriminative, while exposure to passive smoke and biomass fuel for heating were discriminative for women. COPD in never-smokers and ever-smokers was characterised by increased respiratory symptoms, 'respiratory exacerbation' events and increased residual volume/total lung capacity, but only smokers had reduced DLCO/Va and emphysema on chest CT scans.
The study confirmed the substantial burden of COPD among never-smokers, defined the common and gender-specific risk factors for COPD in never-smokers and provided early insight into potential phenotypical differences in COPD between lifelong never-smokers and ever-smokers.
NCT00920348 (ClinicalTrials.gov); study ID number: IRO-93326.
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Additive manufacturing (AM) offers significant potential benefits in the field of drug delivery and pharmaceutical/medical device manufacture. Of AM processes, 3D inkjet printing ...enables precise deposition of a formulation, whilst offering the potential for significant scale up or scale out as a manufacturing platform. This work hypothesizes that suitable solvent based ink formulations can be developed that allow the production of solid dosage forms that meet the standards required for pharmaceutical tablets, whilst offering a platform for flexible and personalized manufacture. We demonstrate this using piezo-activated inkjetting to 3D print ropinirole hydrochloride. The tablets produced consist of a cross-linked poly(ethylene glycol diacrylate) (PEGDA) hydrogel matrix containing the drug, photoinitiated in a low oxygen environment using an aqueous solution of Irgacure 2959. At a Ropinirole HCl loading of 0.41mg, drug release from the tablet is shown to be Fickian. Raman and IR spectroscopy indicate a high degree of cross-linking and formation of an amorphous solid dispersion. This is the first publication of a UV inkjet 3D printed tablet. Consequently, this work opens the possibility for the translation of scalable, high precision and bespoke ink-jet based additive manufacturing to the pharmaceutical sector.
Objectives This study sought to analyze multidetector computed tomography (MDCT) 3-dimensional aortic annular dimensions for the prediction of paravalvular aortic regurgitation (PAR) following ...transcatheter aortic valve replacement (TAVR). Background Moderate or severe PAR after TAVR is associated with increased morbidity and mortality. Methods A total of 109 consecutive patients underwent MDCT pre-TAVR with a balloon expandable aortic valve. Differences between transcatheter heart valve (THV) size and MDCT measures of annular size (mean diameter, area, and circumference) were analyzed concerning prediction of PAR. Patients with THV malposition (n = 7) were excluded. In 50 patients, MDCT was repeated after TAVR to assess THV eccentricity (1 – short diameter/long diameter) and expansion (MDCT measured THV area/nominal THV area). Results Moderate or severe PAR (13 of 102) was associated with THV undersizing (THV diameter – mean diameter = –0.7 ± 1.4 mm vs. 0.9 ± 1.8 mm for trivial to mild PAR, p < 0.01). The difference between THV size and MDCT annular size was predictive of PAR (mean diameter: area under the curve AUC: 0.81, 95% confidence interval CI: 0.68 to 0.88; area: AUC: 0.80, 95% CI: 0.65 to 0.90; circumference: AUC: 0.76, 95% CI: 0.59 to 0.91). Annular eccentricity was not associated with PAR (AUC: 0.58, 95% CI: 0.46 to 0.75). We found that 35.3% (36 of 102) and 45.1% (46 of 102) of THVs were undersized relative to the MDCT mean diameter and area, respectively. THV oversizing relative to the annular area was not associated with THV eccentricity or underexpansion (oversized vs. undersized THVs; expansion: 102.7 ± 5.3% vs. 106.1 ± 5.6%, p = 0.03; eccentricity: median: 1.7% interquartile range: 1.4% to 3.0% vs. 1.7% interquartile range: 1.1% to 2.7%, p = 0.28). Conclusions MDCT-derived 3-dimensional aortic annular measurements are predictive of moderate or severe PAR following TAVR. Oversizing of THVs may reduce the risk of moderate or severe PAR.
The E12-14-012 experiment, performed in Jefferson Lab Hall A, has measured the $(e, e'p)$ cross section in parallel kinematics using a natural argon target. Here, we report the full results of the ...analysis of the data set corresponding to beam energy 2.222 GeV, and spanning the missing momentum and missing energy range $15 \lesssim p_m \lesssim 300$ MeV/c and $12 \lesssim E_m \lesssim 80$ MeV. The reduced cross section, determined as a function of $p_m$ and $E_m$ with $\approx$4\% accuracy, has been fitted using the results of Monte Carlo simulations involving a model spectral function and including the effects of final state interactions. The overall agreement between data and simulations turns out to be quite satisfactory ($\chi^2$/n.d.o.f.=1.9). Furthermore, the resulting spectral function will provide valuable new information, needed for the interpretation of neutrino interactions in liquid argon detectors.
Despite the advancement of additive manufacturing (AM)/3-dimensional (3D) printing, single-step fabrication of multifunctional parts using AM is limited. With the view of enabling multifunctional AM ...(MFAM), in this study, sintering of metal nanoparticles was performed to obtain conductivity for continuous line inkjet printing of electronics. This was achieved using a bespoke three-dimensional (3D) inkjet-printing machine, JETx, capable of printing a range of materials and utilizing different post processing procedures to print multilayered 3D structures in a single manufacturing step. Multiple layers of silver were printed from an ink containing silver nanoparticles (AgNPs) and infrared sintered using a swathe-by-swathe (SS) and layer-by-layer sintering (LS) regime. The differences in the heat profile for the SS and LS was observed to influence the coalescence of the AgNPs. Void percentage of both SS and LS samples was higher toward the top layer than the bottom layer due to relatively less IR exposure in the top than the bottom. The results depicted a homogeneous microstructure for LS of AgNPs and showed less deformation compared to the SS. Electrical resistivity of the LS tracks (13.6 ± 1 μΩ cm) was lower than the SS tracks (22.5 ± 1 μΩ cm). This study recommends the use of LS method to sinter the AgNPs to obtain a conductive track in 25% less time than SS method for MFAM.
Tumor cell extravasation is a key step during cancer metastasis, yet the precise mechanisms that regulate this dynamic process are unclear. We utilized a high-resolution time-lapse intravital imaging ...approach to visualize the dynamics of cancer cell extravasation in vivo. During intravascular migration, cancer cells form protrusive structures identified as invadopodia by their enrichment of MT1-MMP, cortactin, Tks4, and importantly Tks5, which localizes exclusively to invadopodia. Cancer cells extend invadopodia through the endothelium into the extravascular stroma prior to their extravasation at endothelial junctions. Genetic or pharmacological inhibition of invadopodia initiation (cortactin), maturation (Tks5), or function (Tks4) resulted in an abrogation of cancer cell extravasation and metastatic colony formation in an experimental mouse lung metastasis model. This provides direct evidence of a functional role for invadopodia during cancer cell extravasation and distant metastasis and reveals an opportunity for therapeutic intervention in this clinically important process.
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•The dynamics of cancer cell extravasation are visualized using intravital imaging•Intravascular cancer cells generate protrusions that extend between endothelial cells•In vivo localization of MT1-MMP, cortactin, and Tks4/Tks5 identify these as invadopodia•Genetic or pharmacologic inhibition of invadopodia blocks extravasation and metastasis
Tumor cell extravasation is a key step during cancer metastasis, yet the mechanisms that regulate this dynamic process are unclear. Leong et al. show that invadopodia formed by multiple types of cancer cells are required for extravasation in vivo and that inhibition of invadopodia blocks tumor cell extravasation and the subsequent formation of metastases in multiple animal models. This study establishes a direct functional in vivo role for invadopodia in extravasation, revealing an opportunity for therapeutic intervention in this clinically important process.
The rheological behaviour of polymer nanocomposites is very important for polymer processing and understanding the structure-properties relationship. In this paper, the rheological properties of a ...polyamide 12 (PA12) - carbon nanotube (CNT) nanocomposite for laser sintering were studied. Compared to neat PA12, the presence of CNTs resulted in higher storage modulus (G′), loss modulus (G″) and viscosity (η). With an increase in temperature, viscosity showed an unusual increase for both PA12 and the PA12-CNT nanocomposites, which is likely to result from incomplete melting of powder particles. Dynamic mechanical analysis was carried out to examine the effect the CNTs were having on the laser sintered parts. The laser sintered PA12-CNT nanocomposite had an increased elastic modulus compared to that of neat PA12. The CNT and polymer matrix interaction hindered the chain motions, which resulted in higher loss modulus and decreased the thermal expansion coefficient.
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