Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder characterized by abdominal pain and discomfort in association with altered bowel habits. It is estimated to affect 10%-15% of the Western population, and has a large impact on quality of life and (in)direct healthcare costs. IBS is a multifactorial disorder involving dysregulation within the brain-gut axis, and it is frequently associated with gastrointestinal motor and sensory dysfunction, enteric and central nervous system irregularities, neuroimmune dysregulation, and postinfectious inflammation. As with other functional medical disorders, the treatment for IBS can be challenging. Conventional therapy for those with moderate to severe symptoms is largely unsatisfactory, and the development of new and effective drugs is made difficult by the complex pathogenesis, variety of symptoms, and lack of objective clinical findings that are the hallmark of this disorder. Fortunately, research advances over the past several decades have provided insight into potential mechanisms responsible for the pathogenesis of IBS, and have led to the development of several promising pharmaceutical agents. In recent years there has been much publicity over several of these new IBS medications (alosetron and tegaserod) because of their reported association with ischemic colitis and cardiovascular disease. While these agents remain available for use under restricted prescribing programs, this highlights the need for continued development of safe and effective medication for IBS. This article provides a physiologicallybased overview of recently developed and frequently employed pharmaceutical agents used to treat IBS, and discusses some non-pharmaceutical options that may be beneficial in this disorder.

In this paper we develop predictions from models of life-long demographic heterogeneity. These predictions are then compared to observations of mortality in large laboratory populations of Drosophila melanogaster. We find that the demographic heterogeneity models either require levels of variation that far exceed what would be considered biologically plausible, or they predict a much larger number of very old individuals than we actually observe. We conclude that the demographic heterogeneity models are not reasonable explanations of demographic patterns and are weakly motivated biological models.

ERCP in post-PD patients can be performed with a high success rate. We recommend that CEs should be used initially for ERCP in patients with PD and that BAEs be reserved for situation in which CEs have failed to reach the pancreaticobiliary anastomoses.

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