An update of the Worldwide Integrated Assessment (WIA) on systemic insecticides. Part 2: impacts on organisms and ecosystems

New information on the lethal and sublethal effects of neonicotinoids and fipronil on organisms is presented in this review, complementing the previous WIA in 2015. The high toxicity of these systemic insecticides to invertebrates has been confirmed and expanded to include more species and compounds. Most of the recent research has focused on bees and the sublethal and ecological impacts these insecticides have on pollinators. Toxic effects on other invertebrate taxa also covered predatory and parasitoid natural enemies and aquatic arthropods. Little, while not much new information has been gathered on soil organisms. The impact on marine coastal ecosystems is still largely uncharted. The chronic lethality of neonicotinoids to insects and crustaceans, and the strengthened evidence that these chemicals also impair the immune system and reproduction, highlights the dangers of this particular insecticidal classneonicotinoids and fipronil. , withContinued large scale – mostly prophylactic – use of these persistent organochlorine pesticides has the potential to greatly decreasecompletely eliminate populations of arthropods in both terrestrial and aquatic environments. Sublethal effects on fish, reptiles, frogs, birds and mammals are also reported, showing a better understanding of the mechanisms of toxicity of these insecticides in vertebrates, and their deleterious impacts on growth, reproduction and neurobehaviour of most of the species tested. This review concludes with a summary of impacts on the ecosystem services and functioning, particularly on pollination, soil biota and aquatic invertebrate communities, thus reinforcing the previous WIA conclusions (van der Sluijs et al. 2015)

Analyzing solvent effects on halogen-bonded ion pairs with wavefunction methods combined with COSMO

In dieser Dissertation präsentiere ich eine neue Implementierung des COSMO-RI-ADC(2) und COSMO-RI-CC2 zur Berechnung von molekularen vertikalen Anregungsenergien in Lösung unter Verwendung des Post-SCF-Reaktionsfeldschemas. Die wichtigste methodologische Entwicklung der Arbeit war jedoch die erste Implementierung von analytischen Gradienten im angeregten Zustand auf dem COSMO-RI-ADC(2) (post-SCF) Level. Mit diesem Niveau können Photoanregungen und Fluoreszenzemissionen von Komplexen mit Halogenbindungen in Lösung über TD-DFT hinaus untersucht werden

Summary from the NCI clinical trials planning meeting on next generation of clinical trials in non-muscle invasive bladder cancer.

The National Cancer Institute organized a virtual Clinical Trials Planning Meeting (CTPM) on 'Defining the next generation of clinical trials with combination therapies in non-muscle invasive bladder cancer (NMIBC)' led by the Bladder Cancer Task Force of the NCI Genitourinary Cancers Steering Committee. The purpose of this meeting was to accelerate advances in clinical trials for patients with high-risk NMIBC. The meeting delivered a multidisciplinary expert consensus on optimal strategies for next-generation clinical trial designs in NMIBC with prioritization of combination therapies. Two clinical trial concepts were developed for potential implementation within the National Clinical Trials Network

A feasibility study on pellet coating using a high-speed quasi-continuous coater

10.1208/s12249-012-9852-xAAPS PharmSciTech1341276-128

Photoreceptor rescue by an abbreviated human RPGR gene in a murine model of X-linked retinitis pigmentosa

The X-linked RP3 gene codes for the ciliary protein RPGR and accounts for over 10% of inherited retinal degenerations. The critical RPGR-ORF15 splice variant contains a highly repetitive purine-rich linker region that renders it unstable and difficult to adapt for gene therapy. To test the hypothesis that the precise length of the linker region is not critical for function, we evaluated whether AAV-mediated replacement gene therapy with a human ORF15 variant containing in-frame shortening of the linker region could reconstitute RPGR function in vivo. We delivered human RPGR-ORF15 replacement genes with deletion of most (314-codons, “short form”) or 1/3 (126-codons, “long form”) of the linker region to Rpgr null mice. Human RPGR-ORF15 expression was detected post-treatment with both forms of ORF15 transgenes. However, only the long form correctly localized to the connecting cilia and led to significant functional and morphological rescue of rods and cones. Thus the highly repetitive region of RPGR is functionally important but that moderate shortening of its length, which confers the advantage of added stability, preserves its function. These findings provide a theoretical basis for optimizing replacement gene design in clinical trials for X-linked RP3