Purpose
The objective of this study was to incorporate a passive cyclic loading strategy into the infant air-jet dry powder inhaler (DPI) in a manner that provides high efficiency aerosol lung ...delivery and is insensitive to powder mass loadings and the presence of downstream pulmonary mechanics.
Methods
Four unique air-jet DPIs were initially compared and the best performing passive design (PD) was selected for sensitivity analyses. A single preterm
in vitro
nose-throat (NT) model, air source, and nasal interface were utilized throughout. While the majority of analyses were evaluated with a model spray-dried excipient enhanced growth (EEG) formulation, performance of a Surfactant-EEG formulation was also explored for the lead DPI design.
Results
Two devices, PD-2 and PD-3, evaluated in the preterm model achieved an estimated lung delivery efficiency of 60% with the model EEG formulation, and were not sensitive to the loaded dose (10–30 mg of powder). The PD-3 device was also unaffected by the presence of downstream pulmonary mechanics (infant lung model) and had only a minor sensitivity to tripling the volume of the powder reservoir. When using the Surfactant-EEG formulation, increasing the actuation flow rate from 1.7 to 4.0 L/min improved lung delivery by nearly 10%.
Conclusions
The infant air-jet DPI platform was successfully modified with a passive cyclic loading strategy and capable of providing an estimated > 60% lung delivery efficiency of a model spray-dried formulation with negligible sensitivity to powder mass loading in the range of 10–30 mg and could be scaled to deliver much higher doses.
Using only cosmic microwave background polarization data from the polarbear experiment, we measure B-mode polarization delensing on subdegree scales at more than 5σ significance. We achieve a 14% ...B-mode power variance reduction, the highest to date for internal delensing, and improve this result to 22% by applying for the first time an iterative maximum a posteriori delensing method. Our analysis demonstrates the capability of internal delensing as a means of improving constraints on inflationary models, paving the way for the optimal analysis of next-generation primordial B-mode experiments.
We present a measurement of the B-mode polarization power spectrum of the cosmic microwave background (CMB) using data taken from 2014 July to 2016 December with the Polarbear experiment. The CMB ...power spectra are measured using observations at 150 GHz with an instantaneous array sensitivity of on a 670 square degree patch of sky centered at (R.A., decl.) = (+0h12m0s, −59°18′). A continuously rotating half-wave plate is used to modulate polarization and to suppress low-frequency noise. We achieve 32 K arcmin effective polarization map noise with a knee in sensitivity of = 90, where the inflationary gravitational-wave signal is expected to peak. The measured B-mode power spectrum is consistent with a ΛCDM lensing and single dust component foreground model over a range of multipoles 50 ≤ ≤ 600. The data disfavor zero at 2.2 using this range of Polarbear data alone. We cross-correlate our data with Planck full mission 143, 217, and 353 GHz frequency maps and find the low- B-mode power in the combined data set to be consistent with thermal dust emission. We place an upper limit on the tensor-to-scalar ratio r < 0.90 at the 95% confidence level after marginalizing over foregrounds.
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There is a current medical need for a dry powder aerosol delivery device that can be used to efficiently and consistently administer high dose therapeutics, such as inhaled ...antibiotics, surfactants and antivirals, to the lungs of infants. This study considered an infant air-jet dry powder inhaler (DPI) that could be actuated multiple times with minimal user interaction (i.e., a passive cyclic loading strategy) and focused on the development of a metering system that could be tuned for individual powder formulations to maintain high efficiency lung delivery. The metering system consisted of a powder delivery tube (PDT) connecting a powder reservoir with an aerosolization chamber and a powder supporting shelf that held a defined formulation volume. Results indicated that the metering system could administer a consistent dose per actuation after reaching a steady state condition. Modifications of the PDT diameter and shelf volume provided a controllable approach that could be tuned to maximize lung delivery efficiency for three different formulations. Using optimized metering system conditions for each formulation, the infant air-jet DPI was found to provide efficient and consistent lung delivery of aerosols (∼45% of loaded dose) based on in vitro testing with a preterm nose-throat model and limited dose/actuation to <5 mg.
Abstract
High angular resolution cosmic microwave background experiments provide a unique opportunity to conduct a survey of time-variable sources at millimeter wavelengths, a population that has ...primarily been understood through follow-up measurements of detections in other bands. Here we report the first results of an astronomical transient survey with the South Pole Telescope (SPT) using the SPT-3G camera to observe 1500 deg
2
of the southern sky. The observations took place from 2020 March to November in three bands centered at 95, 150, and 220 GHz. This survey yielded the detection of 15 transient events from sources not previously detected by the SPT. The majority are associated with variable stars of different types, expanding the number of such detected flares by more than a factor of two. The stellar flares are unpolarized and bright, in some cases exceeding 1 Jy, and have durations from a few minutes to several hours. Another population of detected events last for 2–3 weeks and appear to be extragalactic in origin. Though data availability at other wavelengths is limited, we find evidence for concurrent optical activity for two of the stellar flares. Future data from SPT-3G and forthcoming instruments will provide real-time detection of millimeter-wave transients on timescales of minutes to months.
The MAJORANA DEMONSTRATOR is an ultra-low-background experiment searching for neutrinoless double-beta decay in Ge76. The heavily shielded array of germanium detectors, placed nearly a mile ...underground at the Sanford Underground Research Facility in Lead, South Dakota, also allows searches for new exotic physics. We present the first limits for trinucleon decay-specific modes and invisible decay modes for Ge isotopes. We find a half-life limit of 4.9×1025 yr for the decay Ge76(ppn)→Zn73 e+π+ and 4.7×1025 yr for the decay Ge76(ppp)→Cu73 e+π+π+. The half-life limit for the invisible triproton decay mode of Ge76 was found to be 7.5×1024 yr.
The development of a non-sputum-based, point-of-care diagnostic test for tuberculosis (TB) is a priority in the global effort to combat this disease, particularly in resource-constrained settings. ...Previous studies have identified host biomarker signatures which showed potential, but there is a need to validate and refine these for development as a test. We recruited 1,403 adults presenting with symptoms suggestive of pulmonary TB at primary healthcare clinics in six countries from West, East and Southern Africa. Of the study cohort, 326 were diagnosed with TB and 787 with other respiratory diseases, from whom we randomly selected 1005 participants. Using Luminex
technology, we measured the levels of 20 host biomarkers in serum samples which we used to evaluate the diagnostic accuracy of previously identified and novel bio-signatures. Our previously identified seven-marker bio-signature did not perform well (sensitivity: 89%, specificity: 60%). We also identified an optimal, two-marker bio-signature with a sensitivity of 94% and specificity of 69% in patients with no history of previous TB. This signature performed slightly better than C-reactive protein (CRP) alone. The cut-off value for a positive diagnosis differed for human immuno-deficiency virus (HIV)-positive and -negative individuals. Notably, we also found that no signature was able to diagnose TB adequately in patients with a prior history of the disease. We have identified a two-marker, pan-African bio-signature which is more robust than CRP alone and meets the World Health Organization (WHO) target product profile requirements for a triage test in both HIV-negative and HIV-positive individuals. This signature could be incorporated into a point-of-care device, greatly reducing the necessity for expensive confirmatory diagnostics and potentially reducing the number of cases currently lost to follow-up. It might also potentially be useful with individuals unable to provide sputum or with paucibacillary disease. We suggest that the performance of TB diagnostic signatures can be improved by incorporating the HIV-status of the patient. We further suggest that only patients who have never had TB be subjected to a triage test and that those with a history of previous TB be evaluated using more direct diagnostic techniques.
Here, we present a measurement of gravitational lensing over 1500deg2 of the Southern sky using SPT-3G temperature data at 95 GHz and 150 GHz taken in 2018. The lensing amplitude relative to a ...fiducial Planck 2018 Lambda cold dark matter ( Λ CDM ) cosmology is found to be 1.020±0.060 , excluding instrumental and astrophysical systematic uncertainties. We conduct extensive systematic and null tests to check the robustness of the lensing measurements, and report a minimum-variance combined lensing power spectrum over angular multipoles of 50<L<2000 , which we use to constrain cosmological models. When analyzed alone and jointly with primary cosmic microwave background (CMB) spectra within the Λ CDM model, our lensing amplitude measurements are consistent with measurements from SPT-SZ, SPTpol, ACT, and Planck. Incorporating loose priors on the baryon density and other parameters including uncertainties on a foreground bias template, we obtain a 1σ constraint on σ8 Ω m 0.25=0.595±0.026 using the SPT-3G 2018 lensing data alone, where σ8 is a common measure of the amplitude of structure today and Ω m is the matter density parameter. Combining SPT-3G 2018 lensing measurements with baryon acoustic oscillation (BAO) data, we derive parameter constraints of σ8=0.810±0.033 , S8≡σ8 ( Ω m /0.3 ) 0.5= 0.836±0.039 , and Hubble constant H0=68.8-1.6+1.3km s -1Mpc-1 . Our preferred S8 value is higher by 1.6 to 1.8σ compared to cosmic shear measurements from DES-Y3, HSC-Y3, and KiDS-1000 at lower redshift and smaller scales. We combine our lensing data with CMB anisotropy measurements from both SPT-3G and Planck to constrain extensions of Λ CDM . Using CMB anisotropy and lensing measurements from SPT-3G only, we provide independent constraints on the spatial curvature of Ω K=0.014-0.026+0.023 (95% C.L.) and the dark energy density of Ω Λ =0.722-0.026+0.031 (68% C.L.). When combining SPT-3G lensing data with SPT-3G CMB anisotropy and BAO data, we find an upper limit on the sum of the neutrino masses of Σmν<0.30eV (95% C.L.). Due to the diferent combination of angular scales and sky area, this lensing analysis provides an independent check on lensing measurements by ACT and Planck.
Coastal soft cliffs in the UK support rich assemblages of invertebrates including species restricted to soft cliffs Howe (Br Wildl 4: 323–331, 2003). Recent analyses have identified a total of 29 ...species confined to coastal soft cliffs, with a further 78 species having a high degree of dependence (Howe et al. Br Wildl 19: 172–181, 2008). A handful of species once more widespread in the UK, both on the coast and inland, such as the Large Mason Bee Osmia xanthomelana and the Long-horned Bee Eucera longicornis, are now found only or mostly at soft cliff localities. Key habitats include bare sand or glacial till, extensive swards of leguminuous and ruderal plants and hydrological features including seepages, pools and reedbeds. Unhindered dynamic processes such as erosion and cliff failure and unimpeded drainage are critical to soft cliffs retaining their invertebrate interest. By far the richest sites for soft cliff invertebrates are on the Dorset and the Isle of Wight coasts, but other important localities include south Devon, the Llyn coast in Gwynedd, north Norfolk, Yorkshire and the south Gower coast. The most obvious threats to soft cliff invertebrates are cliff-protection and stabilization schemes and drainage. However, agricultural improvement of cliff-top hinterlands at many sites restricts nesting and foraging activities to the immediate cliff slopes, and acts to fragment and isolate sections of soft cliff. More sympathetic management of these areas is needed to reconnect sites and their associated invertebrate populations, to reduce a dependence upon the cliff slope and to increase the availability of suitable nesting and foraging habitats.
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