In Vivo Methods to Study Uptake of Nanoparticles into the Brain

Several in vivo techniques have been developed to study and measure the uptake of CNS compounds into the brain. With these techniques, various parameters can be determined after drug administration, including the blood-to-brain influx constant (Kin), the permeability-surface area (PS) product, and the brain uptake index (BUI). These techniques have been mostly used for drugs that are expected to enter the brain via transmembrane diffusion or by carrier-mediated transcytosis. Drugs that have limitations in entering the brain via such pathways have been encapsulated in nanoparticles (based on lipids or synthetic polymers) to enhance brain uptake. Nanoparticles are different from CNS compounds in size, composition and uptake mechanisms. This has led to different methods and approaches to study brain uptake in vivo. Here we discuss the techniques generally used to measure nanoparticle uptake in addition to the techniques used for CNS compounds. Techniques include visualization methods, behavioral tests, and quantitative methods

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Understanding similarities and differences in land use visions for Scotland

The successful transition towards a global society that can live within planetary boundaries is one of the greatest challenges for the twenty-first century. Sustainable land use and land management will be essential to ensure the continued delivery of the ecosystem goods and services needed to support a rapidly growing global population. To support the transition towards sustainable development, decision-makers need to better understand how land use change affects people and the environment. However, these insights are of limited use without societal agreement on future land uses. Understanding synergies and differences between land use visions forms a first step in assessing and comparing alternative pathways towards a sustainable future. This thesis uses a range of methods to understand visions of future land use amongst professional land use stakeholders, society at large, and young people in Scotland. Twenty semi-structured interviews were held with policy experts from the Scottish land use sectors. A nationwide statistically representative web-based survey provided insight into the visions of the Scottish population. And finally, a novel visual interview methodology was used to interview 26 pupils from two high schools in Perthshire. Inductive content analysis and descriptive statistics were used to analyse the results and understand and compare the land use visions of these different groups. As expected, different groups had different visions of future land use. There was, however, general agreement on certain themes, in particular the desire for a more sustainable lifestyle and the importance of a healthy environment. The sectoral stakeholders would like to see more partnerships, dialogue and collaboration; a society that is more engaged and aware about land use; resilient local economies; and short-, medium-, and long-term policies that help to achieve these goals. One of the key challenges for these groups will be how to translate abstract concepts such as ‘healthy ecosystem’ and ‘dialogue and partnerships’ into practice. This clearly requires a shared understanding of what a ‘healthy ecosystem’ means to different stakeholders, as well as appreciation of what true dialogue means and how this can be used to co-create solutions – potentially a radical change from the traditional top-down approaches. The research also identified divisions in Scottish society between those who want to continue a ‘status quo’ lifestyle, and those – in particular younger people (who spent time in the natural environment, through either school or home life) and those from a higher socio-economic background – who want a more sustainable lifestyle and to be more connected with the natural environment. These results are important, as policy makers need to be able to identify the factors that have successfully engaged certain groups and to promote these factors. Programmes that provide access to the natural environment (such as the Duke of Edinburgh’s Award) need to ensure equal opportunities by targeting disadvantaged groups. Simultaneously, it needs to be explored how to encourage those who would like to continue a ‘status quo’ lifestyle into a more sustainable one. Past research has shown how preferences can be influenced and how changes can be initiated by incentives and restrictions in order to promote desired behaviours. The power of the media should be leveraged: programmes such as BBC’s ‘Blue Planet’ highlight how our lifestyle choices impact on the natural environment and can provide the motivation for change. The current issues surrounding Brexit and Climate Change require a national conversation; using methods such as those presented in the thesis to elicit land use visions can help identify the commonalties and differences between stakeholders’ views. This can provide a starting point for dialogue and critical reflection on current instruments and objectives, and how they might be adapted to better reflect Scottish preferences and conditions

Cephalometric assessment of craniofacial dysmorphologies in relation with Msx2 mutations in mouse

To determine the role of Msx2 in craniofacial morphology and growth, we used a mouse model and performed a quantitative morphological characterization of the Msx2 (-/-) and the Msx2 (+/-) phenotype using a 2D cephalometric analysis applied on micrographs.status: publishe

Fish drug analysis—Phish-pharm: A searchable database of pharmacokinetics data in fish

Information about drug residues and pharmacokinetic parameters in aquatic species is relatively sparse. In addition, it is difficult to rapidly compare data between studies due to differences in experimental conditions, such as water temperatures and salinity. To facilitate the study of aquatic species drug metabolism, we constructed a Fish Drug/Chemical Analysis Phish-Pharm (FDA-PP) database. This database consists of more than 400 articles that include data from 90 species (64 genera) of fish. Data fields include genus, species, water temperatures, the average animal weight, sample types analyzed, drug (or chemical) name, dosage, route of administration, metabolites identified, method of analysis, protein binding, clearance, volume of distribution in a central compartment (Vc) or volume of distribution at steady-state (Vd), and drug half-lives (t1/2). Additional fields list the citation, authors, title, and Internet links. The document will be periodically updated, and users are invited to submit additional data. Updates will be announced in future issues ofThe AAPS Journal. This database will be a valuable resource to investigators of drug metabolism in aquatic species as well as government and private organizations involved in the drug approval process for aquatic species