Engineering a static verification tool for GPU kernels

We report on practical experiences over the last 2.5 years related to the engineering of GPUVerify, a static verification tool for OpenCL and CUDA GPU kernels, plotting the progress of GPUVerify from a prototype to a fully functional and relatively efficient analysis tool. Our hope is that this experience report will serve the verification community by helping to inform future tooling efforts. © 2014 Springer International Publishing

Mucus clearance and lung function in cystic fibrosis with hypertonic saline

BACKGROUND: Abnormal homeostasis of the volume of airway surface liquid in patients with cystic fibrosis is thought to produce defects in mucus clearance and airway defense. Through osmotic forces, hypertonic saline may increase the volume of airway surface liquid, restore mucus clearance, and improve lung function. METHODS: A total of 24 patients with cystic fibrosis were randomly assigned to receive treatment with inhaled hypertonic saline (5 ml of 7 percent sodium chloride) four times daily with or without pretreatment with amiloride. Mucus clearance and lung function were measured during 14-day baseline and treatment periods. RESULTS: Long-term inhalation of hypertonic saline without pretreatment with amiloride (i.e., with placebo pretreatment) resulted in a sustained (≥8 hours) increase in 1-hour rates of mucus clearance, as compared with those with amiloride pretreatment (14.0±2.0 vs. 7.0±1.5 percent, respectively; P = 0.02) and increased 24-hour rates of mucus clearance over baseline. Furthermore, inhalation of hypertonic saline with placebo improved the forced expiratory volume in one second (FEV 1) between the baseline period and the treatment period (mean difference, 6.62 percent; 95 percent confidence interval, 1.6 to 11.7; P = 0.02), whereas hypertonic saline with amiloride did not improve FEV 1 (mean difference, 2.9 percent; 95 percent confidence interval, -2.2 to 8.0; P = 0.23). Forced vital capacity (FVC), the forced expiratory flow between 25 and 75 percent of FVC (FEF 25-75), and respiratory symptoms also significantly improved in patients treated with hypertonic saline and placebo, whereas the residual volume as a proportion of total lung capacity (RV:TLC) did not change in either group. A comparison of the changes in lung function in the two groups showed no significant difference. In vitro data suggested that sustained hydration of airway surfaces was responsible for the sustained improvement in mucus clearance, whereas inhibition of osmotically driven water transport by amiloride accounted for the observed loss of clinical benefit. CONCLUSIONS: In patients with cystic fibrosis, inhalation of hypertonic saline produced a sustained acceleration of mucus clearance and improved lung function. This treatment may protect the lung from insults that reduce mucus clearance and produce lung disease

A Trans-Nasal Aerosol Delivery Device for Efficient Pulmonary Deposition

Background: Efficient delivery of aerosols to the lungs via the nasal route has been difficult to achieve, but it may offer benefits over the traditional oral route for a range of patient populations. Because slow, continuous delivery of short-acting agents could improve safety, tolerability, compliance, and efficacy when compared with the rapid, intermittent aerosol treatments delivered by mouthpiece or mask, a novel trans-nasal pulmonary aerosol delivery (tPAD) device was developed. The tPAD incorporates an aerosol particle-size selection chamber and a custom nasal cannula that are specifically optimized for aerosol delivery to the lung via the nasal route. The tPAD device produced a steady aerosol output (∼2 mL/h) from an optimized nasal cannula with negligible rainout in the cannula for up to 8 hours. The generated aerosol particles were small enough to minimize nasal deposition [volume median diameter (VMD) = 1.4 μm]. Methods: In this proof-of-concept study, gamma scintigraphy was used to quantitate deposition efficiency of 99mTc-labeled DTPA in 7% NaCl (hypertonic saline) in healthy human subjects (n = 6) during a short dosing period (15 minutes). A comparison was made with a standard oral jet nebulizer in the same subjects. Results: The tPAD device achieved high pulmonary deposition (39% ± 8%), based on emitted dose, and matched that of the oral jet nebulizer (36% ± 9%). Low fractions of aerosol deposition in the head and nose region were observed for tPAD (6% ± 6%) and jet nebulizer deliver (1% ± 1%) as well. Conclusions: A profile of high pulmonary deposition efficiency and low nasal dose may enable the sustained use of the tPAD platform with a variety of therapeutic agents for a range of pulmonary disorders

Homogeneity of Aerosol Deposition and Mucociliary Clearance are Improved Following Ivacaftor Treatment in Cystic Fibrosis

Background: Using planar gamma scintigraphy of inhaled radioaerosols, we have developed new analytical methods for assessing homogeneity of aerosol deposition and time-dependent particle clearance on a pixel-by-pixel basis, and applied them to a therapeutic cystic fibrosis (CF) study. Methods: At baseline and 1 month after beginning treatment with ivacaftor, a cystic fibrosis transmembrane regulator modulator for CF patients with at least one copy of the G551D mutation (n = 13), initial deposition and subsequent mucociliary clearance (MCC) of radiolabeled particles ( 99m Technetium-sulfur colloid, 5 μm mass median aerodynamic diameter) inhaled under controlled breathing conditions were measured. Results: Improved homogeneity of deposition, that is, decreased areas of higher and lower particle deposition in the lungs, was observed following ivacaftor treatment. The mean number ratio (NR) of pixels with higher deposition, relative to lung size, decreased from 0.14 to 0.09 (p = 0.003) and mean NR of colder pixels decreased from 0.23 to 0.19 (p = 0.004). Particle clearance was also improved following treatment, with mean MCC through 60 minutes equal to 12% versus 24%, without and with treatment, respectively (p = 0.010). Pixel-level analysis of MCC showed that (1) the fraction of pixels clearing >30% at 60 minutes was increased from 0.13 to 0.32 (p = 0.007); and (2) the fraction of pixels clearing <5% at 60 minutes was decreased from 0.54 to 0.37 (p = 0.014), indicating an overall recruitment of more fast-clearing lung regions with ivacaftor treatment. Conclusion: These detailed pixel analyses of deposition and clearance homogeneity may supplement traditional methods that use large regions of interest for assessing efficacy and mechanisms of therapeutic intervention in patients with airways disease

Hypertonic saline has a prolonged effect on mucociliary clearance in adults with cystic fibrosis

Background: Inhaled hypertonic saline (HS) has been shown to increase mucociliary clearance (MCC) and improve clinical outcomes in adults and adolescents with cystic fibrosis (CF). However, in younger children with CF, a large study failed to demonstrate clinical benefits. This discrepancy could reflect pharmacodynamic differences in the MCC response to HS in different populations. We previously demonstrated the absence of a sustained effect of HS on MCC in healthy adults and in this study sought to characterize the durability of the MCC response to HS in adults with CF. Methods: At two study sites, MCC was measured in CF adults using gamma scintigraphy during three separate visits: at baseline, 15 min, and 4 h after a single dose of HS (7% NaCl, 4 mL). Particle clearance rates at these visits were used to assess the durability of the MCC response to HS. Results: The average 90-minute clearance rate measured 4 h after HS was significantly increased (21.81% ± 12.8) when compared to baseline (13.77% ± 8.7, p =.048) and showed no apparent slowing relative to the rate measured 15 min after HS. While not all subjects responded to HS, the acute response strongly predicted the sustained effect in these subjects (r = 0.896, p <.0001). Conclusions: These results suggest that, in contrast to healthy adults, a single dose of HS has a prolonged effect on MCC in adults with CF, which lasts at least 4 h. This may explain its clinical efficacy in this population

The <i>Castalia</i> mission to Main Belt Comet 133P/Elst-Pizarro

We describe Castalia, a proposed mission to rendezvous with a Main Belt Comet (MBC), 133P/Elst-Pizarro. MBCs are a recently discovered population of apparently icy bodies within the main asteroid belt between Mars and Jupiter, which may represent the remnants of the population which supplied the early Earth with water. Castalia will perform the first exploration of this population by characterising 133P in detail, solving the puzzle of the MBC’s activity, and making the first in situ measurements of water in the asteroid belt. In many ways a successor to ESA’s highly successful Rosetta mission, Castalia will allow direct comparison between very different classes of comet, including measuring critical isotope ratios, plasma and dust properties. It will also feature the first radar system to visit a minor body, mapping the ice in the interior. Castalia was proposed, in slightly different versions, to the ESA M4 and M5 calls within the Cosmic Vision programme. We describe the science motivation for the mission, the measurements required to achieve the scientific goals, and the proposed instrument payload and spacecraft to achieve these

Argentine Wheat Industry: Conference Report

Established and supported under the Australian Government’s Cooperative Research Centre Progra

Ultrafine particles in four European urban environments: Results from a new continuous long-term monitoring network

To gain a better understanding on the spatiotemporal variation of ultrafine particles (UFPs) in urban environments, this study reports on the first results of a long-term UFP monitoring network, set up in Amsterdam (NL), Antwerp (BE), Leicester (UK) and London (UK). Total number concentrations and size distributions were assessed during 1e2 years at four fixed urban background sites, supplemented with mobile trailer measurements for co-location monitoring and additional short-term monitoring sites. Intra- and interurban spatiotemporal UFP variation, associations with commonly-monitored pollutants (PM, NOx and BC) and impacts of wind fields were evaluated. Although comparable size distributions were observed between the four cities, source-related differences were demonstrated within specific particle size classes. Total and size-resolved particle number concentrations showed clear traffic-related temporal variation, confirming road traffic as the major UFP contributor in urban environments. New particle formation events were observed in all cities. Correlations with typical traffic-related pollutants (BC and NOx) were obtained for all monitoring stations, except for Amsterdam, which might be attributable to UFP emissions from Schiphol airport. The temporal variation in particle number concentration correlated fairly weakly between the four cities (rs = 0.28 0.50, COD = 0.28 0.37), yet improved significantly inside individual cities (rs = 0.59-0.77). Nevertheless, considerable differences were still obtained in terms of particle numbers (20-38% for total particle numbers and up to 49% for size-resolved particle numbers), confirming the importance of local source contributions and the need for careful consideration when allocating UFP monitoring stations in heterogeneous urban environments