Sustained release microparticles for pulmonary drug delivery.

In this study, several formulation approaches for generating sustained release (SR) microparticles suitable for pulmonary deposition are described. The model drug chosen for investigation was the hydrophilic β2-adrenoceptor agonist, Terbutaline Sulphate (TS), used in the treatment of asthma. A particular challenge to achieving suitable sustained release profiles arose from the high water solubility and ionised state of TS. Initial investigations focused on generating TS microcrystals, which would be subsequently coated with a SR excipient. A controlled crystallization method was developed in which TS was crystallized from an anti-solvent, which contained particle size restricting growth retardants. Significantly smaller crystals were obtained in the presence of growth retardants relative to crystallization without retardants. However, the smallest crystals obtained (3.6 μm) were too large for progression, as the application of a SR coat to such crystals would have increased particle size beyond that suitable for inhalation. The next investigation assessed TS release from a polysaccharide matrix particle containing molecularly dispersed active. Drug release was measured (HPLC) using a custom-built diffusion cell, designed to mimic release at the pulmonary epithelium. Release profiles showed that a degree of SR was possible from polysaccharide-based particles; although, SR was not sufficient for further development. Finally TS nanoparticles, obtained from an emulsion-template process, were encapsulated (spray-drying) within hydrophobic microparticles of respirable particle size. Several optimised formulations of this type provided promising in-vitro sustained release of the active at a variety of drug loadings and in a range of release media. The most useful SR excipient chosen for further development was hydrogenated palm oil, which was observed to coat the nanoparticles effectively. In-vitro deposition profiles were determined for a selection of formulations using an Andersen Cascade Impactor, and it was shown that deposition profiles were formulation-dependant and of size ranges suitable for pulmonary deposition

Glacier algae accelerate melt rates on the south-western Greenland Ice Sheet

Melting of the Greenland Ice Sheet (GrIS) is the largest single contributor to eustatic sea level and is amplified by the growth of pigmented algae on the ice surface, which increases solar radiation absorption. This biological albedo-reducing effect and its impact upon sea level rise has not previously been quantified. Here, we combine field spectroscopy with a radiative-transfer model, supervised classification of unmanned aerial vehicle (UAV) and satellite remote-sensing data, and runoff modelling to calculate biologically driven ice surface ablation. We demonstrate that algal growth led to an additional 4.4–6.0 Gt of runoff from bare ice in the south-western sector of the GrIS in summer 2017, representing 10 %–13 % of the total. In localized patches with high biomass accumulation, algae accelerated melting by up to 26.15±3.77 % (standard error, SE). The year 2017 was a high-albedo year, so we also extended our analysis to the particularly low-albedo 2016 melt season. The runoff from the south-western bare-ice zone attributed to algae was much higher in 2016 at 8.8–12.2 Gt, although the proportion of the total runoff contributed by algae was similar at 9 %–13 %. Across a 10 000 km2 area around our field site, algae covered similar proportions of the exposed bare ice zone in both years (57.99 % in 2016 and 58.89 % in 2017), but more of the algal ice was classed as “high biomass” in 2016 (8.35 %) than 2017 (2.54 %). This interannual comparison demonstrates a positive feedback where more widespread, higher-biomass algal blooms are expected to form in high-melt years where the winter snowpack retreats further and earlier, providing a larger area for bloom development and also enhancing the provision of nutrients and liquid water liberated from melting ice. Our analysis confirms the importance of this biological albedo feedback and that its omission from predictive models leads to the systematic underestimation of Greenland's future sea level contribution, especially because both the bare-ice zones available for algal colonization and the length of the biological growth season are set to expand in the future

The Astropy Problem

The Astropy Project (http://astropy.org) is, in its own words, "a community effort to develop a single core package for Astronomy in Python and foster interoperability between Python astronomy packages." For five years this project has been managed, written, and operated as a grassroots, self-organized, almost entirely volunteer effort while the software is used by the majority of the astronomical community. Despite this, the project has always been and remains to this day effectively unfunded. Further, contributors receive little or no formal recognition for creating and supporting what is now critical software. This paper explores the problem in detail, outlines possible solutions to correct this, and presents a few suggestions on how to address the sustainability of general purpose astronomical software

Mathematical modelling of Toxoplasma gondii transmission: A systematic review

Background: Toxoplasma gondii is a ubiquitous protozoan parasite that can infect virtually all warm-blooded animals. It is the causative agent of toxoplasmosis, a significant public health issue worldwide. Mathematical models are useful to study the transmission dynamics of T. gondii infection in different settings, and may be used to compare the effectiveness of prevention measures. Methods: To obtain an overview of existing mathematical models for transmission of T. gondii, a systematic review was undertaken. The review was conducted according to an a priori protocol and the results were reported according to the PRISMA guidelines. Specific search terms were developed and used in the search of three databases (Scopus, PubMed, and Embase). Results: In total, 484 unique records were retrieved from the systematic search. Among them, 15 studies that used mathematical models to study the transmission of T. gondii. These studies were categorized into four groups based on the primary aims: dynamics of transmission (n = 8), intervention (n = 5), spatial distribution (n = 1), and outbreak investigation (n = 1). Conclusions: Considering the high disease burden caused by T. gondii, the number of studies using mathematical models to understand the transmission dynamics of this parasite and to evaluate the effectiveness of intervention measures was only 15. This systematic review provides an overview of existing mathematical models and identifies the data gaps for model building. The results from this study can be helpful for further development of mathematical models and improved understanding of the transmission dynamics of T. gondii infection

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Towards BioDBcore: a community-defined information specification for biological databases

The present article proposes the adoption of a community-defined, uniform, generic description of the core attributes of biological databases, BioDBCore. The goals of these attributes are to provide a general overview of the database landscape, to encourage consistency and interoperability between resources and to promote the use of semantic and syntactic standards. BioDBCore will make it easier for users to evaluate the scope and relevance of available resources. This new resource will increase the collective impact of the information present in biological database

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Gravitational Waves From Known Pulsars: Results From The Initial Detector Era

We present the results of searches for gravitational waves from a large selection of pulsars using data from the most recent science runs (S6, VSR2 and VSR4) of the initial generation of interferometric gravitational wave detectors LIGO (Laser Interferometric Gravitational-wave Observatory) and Virgo. We do not see evidence for gravitational wave emission from any of the targeted sources but produce upper limits on the emission amplitude. We highlight the results from seven young pulsars with large spin-down luminosities. We reach within a factor of five of the canonical spin-down limit for all seven of these, whilst for the Crab and Vela pulsars we further surpass their spin-down limits. We present new or updated limits for 172 other pulsars (including both young and millisecond pulsars). Now that the detectors are undergoing major upgrades, and, for completeness, we bring together all of the most up-to-date results from all pulsars searched for during the operations of the first-generation LIGO, Virgo and GEO600 detectors. This gives a total of 195 pulsars including the most recent results described in this paper.United States National Science FoundationScience and Technology Facilities Council of the United KingdomMax-Planck-SocietyState of Niedersachsen/GermanyAustralian Research CouncilInternational Science Linkages program of the Commonwealth of AustraliaCouncil of Scientific and Industrial Research of IndiaIstituto Nazionale di Fisica Nucleare of ItalySpanish Ministerio de Economia y CompetitividadConselleria d'Economia Hisenda i Innovacio of the Govern de les Illes BalearsNetherlands Organisation for Scientific ResearchPolish Ministry of Science and Higher EducationFOCUS Programme of Foundation for Polish ScienceRoyal SocietyScottish Funding CouncilScottish Universities Physics AllianceNational Aeronautics and Space AdministrationOTKA of HungaryLyon Institute of Origins (LIO)National Research Foundation of KoreaIndustry CanadaProvince of Ontario through the Ministry of Economic Development and InnovationNational Science and Engineering Research Council CanadaCarnegie TrustLeverhulme TrustDavid and Lucile Packard FoundationResearch CorporationAlfred P. Sloan FoundationAstronom