Hyperglycaemia and Pseudomonas aeruginosa acidify cystic fibrosis airway surface liquid by elevating epithelial monocarboxylate transporter 2 dependent lactate-H⁺ secretion

The cystic fibrosis (CF) airway surface liquid (ASL) provides a nutrient rich environment for bacterial growth including elevated glucose, which together with defective bacterial killing due to aberrant HCO3− transport and acidic ASL, make the CF airways susceptible to colonisation by respiratory pathogens such as Pseudomonas aeruginosa. Approximately half of adults with CF have CF related diabetes (CFRD) and this is associated with increased respiratory decline. CF ASL contains elevated lactate concentrations and hyperglycaemia can also increase ASL lactate. We show that primary human bronchial epithelial (HBE) cells secrete lactate into ASL, which is elevated in hyperglycaemia. This leads to ASL acidification in CFHBE, which could only be mimicked in non-CF HBE following HCO3− removal. Hyperglycaemia-induced changes in ASL lactate and pH were exacerbated by the presence of P. aeruginosa and were attenuated by inhibition of monocarboxylate lactate-H+ co-transporters (MCTs) with AR-C155858. We conclude that hyperglycaemia and P. aeruginosa induce a metabolic shift which increases lactate generation and efflux into ASL via epithelial MCT2 transporters. Normal airways compensate for MCT-driven H+ secretion by secreting HCO3−, a process which is dysfunctional in CF airway epithelium leading to ASL acidification and that these processes may contribute to worsening respiratory disease in CFRD

Forensic Investigation of Sex Crimes and Sexual Offenders

The investigation of sex crimes is a specific function for many law enforcement agencies, requiring an understanding of how to investigate, process crime scenes, interact with victims and offenders, and prepare for court. Drawing on new methods of investigation and the effects of such crimes on victims, Forensic Investigation of Sex Crimes and Sexual Offenders provides in-depth coverage in these areas, offering a valuable supplement for criminal justice courses and an accessible guide for law enforcement.https://dc.etsu.edu/etsu_books/1134/thumbnail.jp

A Bargaining Theory of Conflict with Evolutionary Preferences

Abstract Bargaining models play a central role in international relations, particularly in the study of conflict. A common criticism of this approach is that it fails to account for nonmaterial (e.g., psychological) factors that may influence the bargaining process. We augment a standard bargaining model by allowing actors' preferences over conflict to diverge from the "fitness" payoffs (e.g., resources) typical of such models. Preferences are subject to evolutionary forces-those who attain high fitness reproduce more. We find that Politics and violence are inextricably linked. No contemporary political group highlights this connection more clearly than the Islamic State in Iraq and Syria (ISIS), which has beheaded journalists, massacred minority groups, and glorified these exploits with videos that have spread throughout the world via the Internet. 1 The group's extreme use of violence has led some to conclude that their actions are driven by a violent ideology, rather than by strategic motivations. 2 Others argue that ISIS uses violence in an instrumentally rational manner, potentially to draw international attention and recruits, or to force local populations into submission.