Cosmopolitan Exception

There has been a resurgence of interest in cosmopolitanism in contemporary political theory, based upon the hopeful premise that it heralds an ameliorative response to the malignity of sovereignty's lack and the treacherous violence of sovereignty's excess. The promise of cosmopolitanism inheres in the claim that state sovereignty is and should be supplemented by an international system backed by the legitimacy of international law, grounded in the sovereignty of human rights. Drawing upon Foucault and Agamben, my argument in this essay is that the laudable endeavour of liberal cosmopolitans is flawed in two ways: first, cosmopolitanism cannot escape sovereign violence, because it cannot escape sovereignty; and second, cosmopolitans misconstrue the composition of the very sovereignty they aim to escape. This means that cosmopolitan theorists are unable to identify cosmopolitan practices of sovereignty that also entail forms of violence: cosmopolitan exception. Cosmopolitan exception denotes violent sovereign practices that cannot be differentiated from the protection of rights.

Cough hypersensitivity syndrome is an important clinical concept:a pro/con debate

The major etiologies of chronic cough are generally accepted to consist of upper airway cough syndrome (formerly postnasal drip syndrome), eosinophilic airway inflammation (asthma, nonasthmatic eosinophilic bronchitis), and gastroesophageal reflux disease (GERD). However, only a small percentage of patients with these very common conditions suffers from chronic cough. Furthermore, acute cough due to viral upper respiratory tract infection (URI) is almost always a transient, self-limited condition, yet in a small subgroup of patients, URI heralds the onset of chronic, refractory cough. The cough hypersensitivity syndrome has been proposed to explain the occurrence of chronic cough in a subgroup of patients exposed to the same putative triggers as the vast majority of the population in whom chronic cough does not result. Although conceptually the cough hypersensitivity syndrome may be intellectually satisfying, differences of opinion remain as to whether this newly recognized entity is of clinical significance, i.e., useful for the treatment of patients suffering from chronic cough. The Third American Cough Conference, held in New York in June 2011, provided an ideal forum for the debate of this issue between two internationally recognized authorities in the field of cough.

Northern Ireland: 20 Years After the Cease-Fires

In the closing months of 1994, the principal paramilitary organizations in Northern Ireland declared that their campaigns of violence were at an end. The cease-fires called by republican and loyalist groupings represented the most significant heralds of a complex process of conflict transformation that continues to unfold even twenty years on. In this introduction, we set out to map the key developments that have shaped the tortuous narrative of the Northern Irish 'peace process', thereby providing the historical backdrop for the articles that follow. While remarkable progress has been made over the two decades since the paramilitary cease-fires, the political context and future of the region remain rather more fraught than is often assumed abroad. It is perhaps best, then, to speak of the six counties in terms not of resolution but rather of ambiguity. Twenty years on from the optimism that greeted the paramilitary cease-fires, Northern Ireland retains the essential 'inbetweenness' of a political space that has moved from a 'long war' through a 'long peace' and into a profoundly undecided future. © 2014 Taylor & Francis Group, LLC.

Vitamin D3 suppresses morphological evolution of the cribriform cancerous phenotype

Development of cribriform morphology (CM) heralds malignant change in human colon but lack of mechanistic understanding hampers preventive therapy. This study investigated CM pathobiology in three-dimensional (3D) Caco-2 culture models of colorectal glandular architecture, assessed translational relevance and tested effects of 1,25(OH)2D3, the active form of vitamin D. CM evolution was driven by oncogenic perturbation of the apical polarity (AP) complex comprising PTEN, CDC42 and PRKCZ (phosphatase and tensin homolog, cell division cycle 42 and protein kinase C zeta). Suppression of AP genes initiated a spatiotemporal cascade of mitotic spindle misorientation, apical membrane misalignment and aberrant epithelial configuration. Collectively, these events promoted “Swiss cheese-like” cribriform morphology (CM) comprising multiple abnormal “back to back” lumens surrounded by atypical stratified epithelium, in 3D colorectal gland models. Intestinal cancer driven purely by PTEN-deficiency in transgenic mice developed CM and in human CRC, CM associated with PTEN and PRKCZ readouts. Treatment of PTEN-deficient 3D cultures with 1,25(OH)2D3 upregulated PTEN, rapidly activated CDC42 and PRKCZ, corrected mitotic spindle alignment and suppressed CM development. Conversely, mutationally-activated KRAS blocked 1,25(OH)2D3 rescue of glandular architecture. We conclude that 1,25(OH)2D3 upregulates AP signalling to reverse CM in a KRAS wild type (wt), clinically predictive CRC model system. Vitamin D could be developed as therapy to suppress inception or progression of a subset of colorectal tumors.