The problem of constitutional legitimation: what the debate on electoral quotas tells us about the legitimacy of decision-making rules in constitutional choice

Proponents of electoral quotas have a ‘dependent interpretation’ of democracy, i.e. they have formed an opinion on which decision-making rules are fair on the basis of their prior approval of the outcomes these rules are likely to generate. The article argues that this position causes an irresolvable problem for constitutional processes that seek to legitimately enact institutional change. While constitutional revision governed by formal equality allows the introduction of electoral quotas, this avenue is normatively untenable for proponents of affirmative action if they are consistent with their claim that formal equality reproduces biases and power asymmetries at all levels of decision-making. Their critique raises a fundamental challenge to the constitutional revision rule itself as equally unfair. Without consensus on the decision-making process by which new post-constitutional rules can be legitimately enacted, procedural fairness becomes an issue impossible to resolve at the stage of constitutional choice. This problem of legitimation affects all instances of constitutional choice in which there are opposing views not only about the desired outcome of the process but also about the decision-making rules that govern constitutional choice

Germline selection shapes human mitochondrial DNA diversity.

Approximately 2.4% of the human mitochondrial DNA (mtDNA) genome exhibits common homoplasmic genetic variation. We analyzed 12,975 whole-genome sequences to show that 45.1% of individuals from 1526 mother-offspring pairs harbor a mixed population of mtDNA (heteroplasmy), but the propensity for maternal transmission differs across the mitochondrial genome. Over one generation, we observed selection both for and against variants in specific genomic regions; known variants were more likely to be transmitted than previously unknown variants. However, new heteroplasmies were more likely to match the nuclear genetic ancestry as opposed to the ancestry of the mitochondrial genome on which the mutations occurred, validating our findings in 40,325 individuals. Thus, human mtDNA at the population level is shaped by selective forces within the female germ line under nuclear genetic control, which ensures consistency between the two independent genetic lineages.NIHR, Wellcome Trust, MRC, Genomics Englan

Gastric cancer, version 2.2013: featured updates to the NCCN Guidelines

The NCCN Clinical Practice Guidelines in Oncology for Gastric Cancer provide evidence- and consensus-based recommendations for a multidisciplinary approach for the management of patients with gastric cancer. For patients with resectable locoregional cancer, the guidelines recommend gastrectomy with a D1+ or a modified D2 lymph node dissection (performed by experienced surgeons in high-volume centers). Postoperative chemoradiation is the preferred option after complete gastric resection for patients with T3-T4 tumors and node-positive T1-T2 tumors. Postoperative chemotherapy is included as an option after a modified D2 lymph node dissection for this group of patients. Trastuzumab with chemotherapy is recommended as first-line therapy for patients with HER2-positive advanced or metastatic cancer, confirmed by immunohistochemistry and, if needed, by fluorescence in situ hybridization for IHC 2+

Esophageal and esophagogastric junction cancers, version 1.2015

Esophageal cancer is the sixth most common cause of cancer deaths worldwide. Adenocarcinoma is more common in North America and Western European countries, originating mostly in the lower third of the esophagus, which often involves the esophagogastric junction (EGJ). Recent randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival in patients with resectable cancer. Targeted therapies with trastuzumab and ramucirumab have produced encouraging results in the treatment of advanced or metastatic EGJ adenocarcinomas. Multidisciplinary team management is essential for patients with esophageal and EGJ cancers. This portion of the NCCN Guidelines for Esophageal and EGJ Cancers discusses management of locally advanced adenocarcinoma of the esophagus and EGJ