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The present results will be also useful to predict EI/MS spectrum and fragmentation pathways of other members of the tabun family, namely, the O-alkyl/cycloalkyl N,N-dialkyl (methyl, ethyl, isopropyl, or propyl) phosphoramidocyanidates. © 2020 John Wiley & Sons, Ltd.The contribution of microglia in neurological disorders is emerging as a leading disease driver rather than a consequence of pathology. RNAseT2-deficient leukoencephalopathy is a severe childhood white matter disorder affecting patients in their first year of life and mimicking a cytomegalovirus brain infection. The early onset and resemblance of the symptoms to a viral infection suggest an inflammatory and embryonic origin of the pathology. There are no treatments available for this disease as our understanding of the cellular drivers of the pathology are still unknown. In this study, using a zebrafish mutant for the orthologous rnaset2 gene, we have identified an inflammatory signature in early development and an antiviral immune response in mature adult brains. Using the optical transparency and the ex utero development of the zebrafish larvae we studied immune cell behavior during brain development and identified abnormal microglia as an early marker of pathology. Live imaging and electron microscopy identified that mutant microglia displayed an engorged morphology and were filled with undigested apoptotic cells and undigested substrate. Using microglia-specific depletion and rescue experiments, we identified microglia as drivers of this embryonic phenotype and potential key cellular player in the pathology of RNAseT2-deficient leukoencephalopathy. Our zebrafish model also presented with reduced survival and locomotor defects, therefore recapitulating many aspects of the human disease. Our study therefore placed our rnaset2 mutant at the forefront of leukodystrophy preclinical models and highlighted tissue-specific approaches as future therapeutic avenues. © 2020 The Authors. selleck products Glia published by Wiley Periodicals, Inc.Throughout the world, women involved in criminal justice systems often present with substantial needs and vulnerabilities. Diverting vulnerable people away from prison is government policy in England and Wales, but full psychiatric and social assessments are expensive and hard to access. A screening and quick response initiative – alternatives to custodial remand for women (ACRW) – was implemented across three areas of London (West, South and East) to supplement existing court liaison and diversion services, to assess the feasibility of a supplementary custodial remand service as part of a women’s specialist service pathway in the criminal justice system in England. Three mental health trusts and two voluntary sector providers offered this service enhancement – a screening and service link provision in three London boroughs between 2012 and 2014. We conducted a service evaluation using routinely collected service use record data. The service made 809 contacts, of whom 104 had contact on multiple occasions. Mafrom offending. © 2020 The Authors. Criminal Behaviour and Mental Health published by John Wiley & Sons Ltd.Double ruthenium(II)-catalyzed alkyne annulations of quinones were accomplished. Thus, we report a strategy that provides step-economical access to valuable quinones with a wide range of applications. C-H/N-H activations for alkyne annulations of naphthoquinones provided challenging polycyclic quinoidal compounds by forming four new bonds in one step. The singular power of the thus-obtained compounds was reflected by their antileukemic activity. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.PURPOSE To examine the RWE U.S. commercial health plans cite in their specialty drug coverage decisions. METHODS We used the Tufts Medical Center Specialty Drug Evidence and Coverage Database to identify specialty drug coverage decisions (n = 7267) issued by 17 large commercial health plans. We categorized the clinical evidence plans cited in these coverage decisions (n = 5227) as randomized controlled trials (RCTs), RWE studies, and other clinical studies (studies other than RCT or RWE study). We categorized RWE studies with respect to study type, for example, case series, studies based on medical records, and so on. We compared the frequency that plans cited different categories of RWE, cited RWE for different diseases, and cited RWE for drugs on the market for different time periods. RESULTS RWE comprised 16% of cited clinical studies. Health plans cited RWE with different frequencies (5%-31% of the cited clinical evidence). Overall, plans cited RWE categorized as medical records most often (26% of cited RWE studies). Plans varied in the frequency they cited different RWE categories. Plans most frequently cited RWE for gastroenterological diseases (35% of clinical study citations) and least frequently for respiratory diseases (11% of clinical study citations). Plans cited RWE more for drugs that have long been on the market. CONCLUSIONS Health plans varied with respect to the number and types of RWE studies they cited in their specialty drug coverage decisions. Plans cited RWE more often for some diseases than others, and cited more RWE for older drugs. © 2020 John Wiley & Sons Ltd.The pentamethylcyclopentadienyl N-heterocyclic carbene nickel complex [Ni(η 5 -C 5 Me 5 )Cl(IMes)] (IMes = 1,3-dimesitylimidazol-2-ylidene) efficiently catalyses the anti-Markovnikov hydroboration of alkenes with catecholborane in the presence of a catalytic amount of potassium tert -butoxide, and joins the very exclusive club of nickel catalysts for this important transformation. Interestingly, the regioselectivity can be reversed in some cases by using pinacolborane instead of catecholborane. Mechanistic investigations involving control experiments, 1 H and 11 B NMR spectroscopy, cyclic voltammetry, piezometric measurements and DFT calculations suggest an initial reduction of the Ni(II) precursor to a Ni(I) active species with the concomitant release of H 2 . The crucial role of the alkoxo-catecholato-borohydride species resulting from the reaction of potassium tert -butoxide with catecholborane in the formation of an intermediate nickel-hydride species that would then be reduced a Ni(I) active species, is highlighted.