The impending demise of the WTO Appellate Body: from centrepiece to historical relic?

The current crisis engulfing the multilateral trading system has crystalized in the dispute over the (re-)appointment of the members of the World Trade Organization\u27s Appellate Body. While the legislative arm of the organization has never lived up to its potential, its dispute settlement arm with the Appellate Body at its apex was seen as a lodestar for other international courts and tribunals. The United States has taken issue not only with individual decisions of the Appellate Body (as well as individual Appellate Body members), but with the institution as such. The article recounts the important institutional redesign that has led to the Appellate Body becoming the World Trade Organization\u27s institutional centerpiece . These very same developments are now destined to lead to the Appellate Body\u27s downfall with potential reverberations for the entire World Trade Organization\u27s dispute settlement process. Moreover, it threatens the institution as a whole, unless some last minute compromise can be found between various competing visions of global economic governance

Association of CR1, CLU and PICALM with Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals

In this study, we assess 34 of the most replicated genetic associations for Alzheimer's disease (AD) using data generated on Affymetrix SNP 6.0 arrays and imputed at over 5.7 million markers from a unique cohort of over 1600 neuropathologically defined AD cases and controls (1019 cases and 591 controls). Testing the top genes from the AlzGene meta-analysis, we confirm the well-known association with APOE single nucleotide polymorphisms (SNPs), the CLU, PICALM and CR1 SNPs recently implicated in unusually large data sets, and previously implicated CST3 and ACE SNPs. In the cases of CLU, PICALM and CR1, as well as in APOE, the odds ratios we find are slightly larger than those previously reported in clinical samples, consistent with what we believe to be more accurate classification of disease in the clinically characterized and neuropathologically confirmed AD cases and controls

A neural signature of metabolic syndrome

That metabolic syndrome (MetS) is associated with age‐related cognitive decline is well established. The neurobiological changes underlying these cognitive deficits, however, are not well understood. The goal of this study was to determine whether MetS is associated with regional differences in gray‐matter volume (GMV) using a cross‐sectional, between‐group contrast design in a large, ethnically homogenous sample. T1‐weighted MRIs were sampled from the genetics of brain structure (GOBS) data archive for 208 Mexican‐American participants: 104 participants met or exceeded standard criteria for MetS and 104 participants were age‐ and sex‐matched metabolically healthy controls. Participants ranged in age from 18 to 74 years (37.3 ± 13.2 years, 56.7% female). Images were analyzed in a whole‐brain, voxel‐wise manner using voxel‐based morphometry (VBM). Three contrast analyses were performed, a whole sample analysis of all 208 participants, and two post hoc half‐sample analyses split by age along the median (35.5 years). Significant associations between MetS and decreased GMV were observed in multiple, spatially discrete brain regions including the posterior cerebellum, brainstem, orbitofrontal cortex, bilateral caudate nuclei, right parahippocampus, right amygdala, right insula, lingual gyrus, and right superior temporal gyrus. Age, as shown in the post hoc analyses, was demonstrated to be a significant covariate. A further functional interpretation of the structures exhibiting lower GMV in MetS reflected a significant involvement in reward perception, emotional valence, and reasoning. Additional studies are needed to characterize the influence of MetS\u27s individual clinical components on brain structure and to explore the bidirectional association between GMV and MetS