Optical diagnostics studies of air flow and powder fluidisation in Nexthaler®. Part II: Use of fluorescent imaging to characterise transient release of fines from a dry powder inhaler

© 2018 The fine particle fraction is a key indicator of therapeutic effectiveness of inhaled pharmaceutical aerosols. This paper presents a fluorescence imaging technique to visualise and characterise the emission of active pharmaceutical ingredient (API) fines in model formulations containing coarse lactose carrier and 1.5–2 μm diameter fluorescent microspheres (model API fines). A two-camera arrangement was used to acquire simultaneous images of spatial and temporal distribution of model API fines and fluidised powder formulation near the mouthpiece exit of a DPI. Digital image analysis showed that the model API fines were released along with the bulk of the powder dose. More rapidly accelerating airflows were found to cause earlier release of API fines. The fluorescence imaging technique analyses a substantial fraction of the aerosol plume and was found to provide effective time-resolved characterisation of the de-aggregation and release of API fines with consistent results across a wide range of model API concentrations. Future studies should demonstrate the usefulness of the fluorescence imaging technique across different formulations and DPI devices

Optical diagnostics study of air flow and powder fluidisation in Nexthaler (R)-Part I: Studies with lactose placebo formulation

Effective drug delivery to the lungs by a DPI device requires the air-stream through the device to have sufficient power to aerosolise the powder. Furthermore, sufficient turbulence must be induced, along with particle-wall and particle-particle collisions, in order to de-aggregate small drug particles from large carrier particles. As a result, the emitted and the fine particle doses produced by many commercially available DPI devices tend to be strongly affected by the natural inter-patient variability of the inhaled air flow. The Nexthaler® is a multi-dose breath-actuated dry-powder inhaler with minimum drug delivery-flow rate dependency and incorporating a dose protector. The actuation mechanism of the dose-protector ensures that the dose is only exposed to the inhaled air flow if the flow has sufficient power to cause complete aerosolisation. For this study, a proprietary lactose placebo powder blend was filled into “transparent “ Nexthalers® to allow application of high speed imaging and particle image velocimetry (PIV) techniques to successfully interrogate and reveal details of the powder entrainment and emission processes coupled with characterisation of the flow environment in the vicinity of the mouthpiece exit. The study showed that fluidisation of the bulk of the powder occurs very quickly (~20 ms) after withdrawal of the dose protector followed by powder emission from the device within ~50 ms thereafter. The bulk of the metered placebo dose was emitted within 100-200 ms. The visualisation study also revealed that a very small fraction of powder fines is emitted whilst the dose protector still covers the dosing cup as the flow rate through the device accelerates. The PIV results show that the flow exiting the device is highly turbulent with a rotating flow structure, which forces the particles to follow internal paths having a high probability of wall impacts, suggesting that the flow environment inside the Nexthaler® DPI will be very beneficial for carrier-drug de-aggregation

Prevalence of hypospadias in Italy according to severity, gestational age and birthweight: an epidemiological study

<p>Abstract</p> <p>Background</p> <p>Hypospadias is a congenital displacement of the urethral meatus in male newborns, being either an isolated defect at birth or a sign of sexual development disorders. The aim of this study was to assess the prevalence rate of hypospadias in different Districts of Italy, in order to make a comparison with other countries all over the world.</p> <p>Methods</p> <p>We reviewed all the newborns file records (years 2001–2004) in 15 Italian Hospitals.</p> <p>Results</p> <p>We found an overall hypospadias prevalence rate of 3.066 ± 0.99 per 1000 live births (82.48% mild hypospadias, 17.52% moderate-severe). In newborns Small for Gestational Age (birthweight < 10^thpercentile) of any gestational age the prevalence rate of hypospadias was 6.25 per 1000 live births. Performing multivariate logistic regression analysis for different degrees of hypospadias according to severity, being born SGA remained the only risk factor for moderate-severe hypospadias (p = 0.00898) but not for mild forms (p > 0.1).</p> <p>Conclusion</p> <p>In our sample the prevalence of hypospadias results as high as reported in previous European and American studies (3–4 per 1000 live births). Pathogenesis of isolated hypospadias is multifactorial (genetic, endocrine and environmental factors): however, the prevalence rate of hypospadias is higher in infants born small for gestational age than in newborns with normal birth weight.</p

Pre-Flight Calibration of the Mars 2020 Rover Mastcam Zoom (Mastcam-Z) Multispectral, Stereoscopic Imager

The NASA Perseverance rover Mast Camera Zoom (Mastcam-Z) system is a pair of zoomable, focusable, multi-spectral, and color charge-coupled device (CCD) cameras mounted on top of a 1.7 m Remote Sensing Mast, along with associated electronics and two calibration targets. The cameras contain identical optical assemblies that can range in focal length from 26 mm (25.5∘×19.1∘ FOV) to 110 mm (6.2∘×4.2∘ FOV) and will acquire data at pixel scales of 148-540 μm at a range of 2 m and 7.4-27 cm at 1 km. The cameras are mounted on the rover’s mast with a stereo baseline of 24.3±0.1 cm and a toe-in angle of 1.17±0.03∘ (per camera). Each camera uses a Kodak KAI-2020 CCD with 1600×1200 active pixels and an 8 position filter wheel that contains an IR-cutoff filter for color imaging through the detectors’ Bayer-pattern filters, a neutral density (ND) solar filter for imaging the sun, and 6 narrow-band geology filters (16 total filters). An associated Digital Electronics Assembly provides command data interfaces to the rover, 11-to-8 bit companding, and JPEG compression capabilities. Herein, we describe pre-flight calibration of the Mastcam-Z instrument and characterize its radiometric and geometric behavior. Between April 26thth and May 9thth, 2019, ∼45,000 images were acquired during stand-alone calibration at Malin Space Science Systems (MSSS) in San Diego, CA. Additional data were acquired during Assembly Test and Launch Operations (ATLO) at the Jet Propulsion Laboratory and Kennedy Space Center. Results of the radiometric calibration validate a 5% absolute radiometric accuracy when using camera state parameters investigated during testing. When observing using camera state parameters not interrogated during calibration (e.g., non-canonical zoom positions), we conservatively estimate the absolute uncertainty to be 0.2 design requirement. We discuss lessons learned from calibration and suggest tactical strategies that will optimize the quality of science data acquired during operation at Mars. While most results matched expectations, some surprises were discovered, such as a strong wavelength and temperature dependence on the radiometric coefficients and a scene-dependent dynamic component to the zero-exposure bias frames. Calibration results and derived accuracies were validated using a Geoboard target consisting of well-characterized geologic samples

Mastcam-Z multispectral database from the Perseverance rover’s traverse in the Jezero crater floor, Mars (sols 0-380)

NASA’s Mars-2020 Perseverance rover spent its first year in Jezero crater studying the mafic lava flows of the Máaz formation and the ultramafic cumulates of the Séítah formation. Perseverance’s Mastcam-Z instrument, a pair of multispectral, stereoscopic zoom-lens cameras, provides broadband red/green/blue (RGB), narrowband visible to near-infrared color (VNIR, 440-1020 nm wavelength range). We compiled Mastcam-Z spectra from Perseverance’s exploration of the Jezero crater floor in the first 380 sols of its mission. Here, we provide a database of ~2400 representative spectra with extensive metadata, and the locations of the regions of interest (ROIs) from which the spectra were extracted. We also include “natural color” red, green, blue (RGB) images for context, “enhanced color images” derived by stretching narrowband images, and “decorrelation stretch” (DCS) images. This dataset can serve as a baseline to interpret future observations from Perseverance’s ongoing exploration of Jezero crater, Mars

Mastcam-Z multispectral database from the Perseverance rover’s traverse through the Jezero fan front, Mars (sols 0-707)

During its first 700 sols of exploration, NASA’s Mars-2020 Perseverance rover explored the igneous units of the Jezero crater floor and the sedimentary strata of the western Jezero fan front. The rover’s Mastcam-Z instrument, a pair of multispectral, stereoscopic zoom-lens cameras, provides broadband red/green/blue (RGB), narrowband visible to near-infrared color (VNIR, 440-1020 nm wavelength range). Here, we provide a database of Mastcam-Z spectra and multispectral image products from sols 0-707. These include: the locations of the regions of interest (ROIs) from which the spectra were extracted; “natural color” red, green, blue (RGB) images for context; “enhanced color images” derived by stretching narrowband images; and “decorrelation stretch” (DCS) images that highlight the spectral diversity in left- and right-eye images. This dataset has been calibrated using Version 2 of Mastcam-Z’s radiometric calibration pipeline, which improves upon the calibration of the first dataset for sols 0-380 archived as Rice et al. (2022, https://doi.org/10.25710/bhyk-kc32)

Characterization and quantitation of short chain fructooligosaccharides and inulooligosaccharides in fermented milks by high-performance anion-exchange chromatography with pulsed amperometric detection

With the increased interest in the possible link between fructooligosaccharides (FOS) intake from functional foods and health, the need for reliable data on the individual FOS content of those foods has become very important. In this study a new high-performance anion-exchange chromatography coupled to pulsed amperometric detection (HPAEC-PAD) method is described for the selective determination of short-chain FOS and inulooligosaccharides (IOS) present in the investigated prebiotic food ingredients. Response factor of PAD was investigated in relationship with degree of polymerization and isomers. The developed HPAEC-PAD method has been applied to characterize short-chain oligosaccharides of the inulin series with DP ranging from DP3 to DP7 and IOS from DP2 to DP7. Their quantification in commercial water-soluble fibers of relevant importance as prebiotic food ingredient added in fermented milks has been performed. in order to evaluate the reliability of the proposed method, results have been compared with those obtained by the official enzymatic method. Furthermore, this new HPAEC-PAD method may contribute to clarify the real importance, prebiotic effectiveness and biological role of these carbohydrates