24 research outputs found

    Enantioselective nickel-catalyzed intramolecular allylic alkenylations enabled by reversible alkenylnickel E/Z isomerization

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    Enantioselective nickel-catalyzed arylative cyclizations of substrates containing a Z-allylic phosphate tethered to an alkyne are described. These reactions give multisubstituted chiral aza- and carbocycles, and are initiated by the addition of an arylboronic acid to the alkyne, followed by cyclization of the resulting alkenylnickel species onto the allylic phosphate. The reversible E/Z isomerization of the alkenylnickel species is essential for the success of the reactions

    The trans-ancestral genomic architecture of glycemic traits

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    Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe

    Contemporary trends in PGD incidence, outcomes, and therapies

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    BackgroundWe sought to describe trends in extracorporeal membrane oxygenation (ECMO) use, and define the impact on PGD incidence and early mortality in lung transplantation.MethodsPatients were enrolled from August 2011 to June 2018 at 10 transplant centers in the multi-center Lung Transplant Outcomes Group prospective cohort study. PGD was defined as Grade 3 at 48 or 72 hours, based on the 2016 PGD ISHLT guidelines. Logistic regression and survival models were used to contrast between group effects for event (i.e., PGD and Death) and time-to-event (i.e., death, extubation, discharge) outcomes respectively. Both modeling frameworks accommodate the inclusion of potential confounders.ResultsA total of 1,528 subjects were enrolled with a 25.7% incidence of PGD. Annual PGD incidence (14.3%-38.2%, p&nbsp;=&nbsp;.0002), median LAS (38.0-47.7 p&nbsp;=&nbsp;.009) and the use of ECMO salvage for PGD (5.7%-20.9%, p&nbsp;=&nbsp;.007) increased over the course of the study. PGD was associated with increased 1 year mortality (OR 1.7 [95% C.I. 1.2, 2.3], p&nbsp;=&nbsp;.0001). Bridging strategies were not associated with increased mortality compared to non-bridged patients (p&nbsp;=&nbsp;.66); however, salvage ECMO for PGD was significantly associated with increased mortality (OR 1.9 [1.3, 2.7], p&nbsp;=&nbsp;.0007). Restricted mean survival time comparison at 1-year demonstrated 84.1 days lost in venoarterial salvaged recipients with PGD when compared to those without PGD (ratio 1.3 [1.1, 1.5]) and 27.2 days for venovenous with PGD (ratio 1.1 [1.0, 1.4]).ConclusionsPGD incidence continues to rise in modern transplant practice paralleled by significant increases in recipient severity of illness. Bridging strategies have increased but did not affect PGD incidence or mortality. PGD remains highly associated with mortality and is increasingly treated with salvage ECMO

    'Burqa avenger': law and religious practices in secular space

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    The current debate over the hijab is often understood through the lens of a ‘clash of civilizations’ between a tolerant ‘secular’ ‘West’ and a chauvinist ‘religious’ ‘East’. The article argues that this polarization is the result of a specific secular semiotic understanding of religion and religious practices which is nowadays embedded in western law. In my analysis, secular’s normative assumptions, played around the control of women’s bodies and the definition of religious symbols in the public sphere, work as a marker of ‘citizenship’ and ‘racialized religious belonging’. Through women’s bodies, western/secular law creates a link between gender, religion, ethnicity and belonging which forms a specific law and religious subject. Thus, secularism emerges not as the separation between private and public, state and religion, but as the reconfiguration of religious practices and sensitivities in the public secular space through the control of the visible
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