Optimal group testing designs for estimating prevalence with uncertain testing errors

We construct optimal designs for group testing experiments where the goal is to estimate the prevalence of a trait by using a test with uncertain sensitivity and specificity. Using optimal design theory for approximate designs, we show that the most efficient design for simultaneously estimating the prevalence, sensitivity and specificity requires three different group sizes with equal frequencies. However, if estimating prevalence as accurately as possible is the only focus, the optimal strategy is to have three group sizes with unequal frequencies. On the basis of a chlamydia study in the U.S.A., we compare performances of competing designs and provide insights into how the unknown sensitivity and specificity of the test affect the performance of the prevalence estimator. We demonstrate that the locally D- and Ds-optimal designs proposed have high efficiencies even when the prespecified values of the parameters are moderately misspecified

Bile acids cause relaxation of the lower esophageal sphincter through G-protein-coupled bile acid receptors

AbstractObjectivesBile acids inhibit contraction of the gallbladder and intestine through the G-protein-coupled bile acid receptor (GPBAR). Perfusion of the esophagus with bile and acid (HCl) decreases lower esophageal sphincter (LES) pressure. The effects of bile acids on LES motility are not clear. The purpose of the present study was to investigate the effects of bile acids on LES motility in vitro.Materials and MethodsWe measured the relaxation of muscle strips isolated from guinea pig and rat LES caused by bile acids or the selective GPBAR agonist RG-239. Reverse transcription polymerase chain reaction (RT-PCR) was performed to determine GPBAR expression in rat LES.ResultsIn carbachol-contracted guinea pig LES strips, lithocholic acid (LCA), deoxycholic acid (DCA), chenodeoxycholic acid (CDCA), and cholic acid (CA) produced relaxation in a concentration-dependent manner. The relative potency was LCA ≥ DCA > CDCA > CA. RG-239 also induced concentration-dependent relaxation. This suggests that GPBAR mediates relaxation in guinea pig LES. DCA-induced LES relaxation was attenuated by the protein kinase A inhibitor KT 5720 but not by the protein kinase G inhibitor KT 5823 or the NO synthase inhibitor L-NNA. This suggests the involvement of cAMP. Separately, in endothelin-1-contracted rat LES strips, bile acids induced relaxation. The relative potency was LCA = DCA > CDCA > CA. RT-PCR revealed GPBAR expression in rat LES.ConclusionThese results demonstrate that bile acids cause relaxation of guinea pig and rat LES through GPBAR

Cysteinyl Leukotriene Receptor Type 1 (CysLT1) Mediates Contraction of the Guinea Pig Lower Esophageal Sphincter

AbstractObjectiveLeukotriene D4 (LTD4) causes contraction of the cat lower esophageal sphincter. The effects of leukotrienes in the guinea pig lower esophageal sphincter and the cysteinyl leukotriene receptor (CysLT) subtype that mediate this contraction are not known. The purpose of the present study was to characterize the CysLT receptors in the guinea pig lower esophageal sphincter.Materials and MethodsWe measured the contractions of transverse strips from the guinea pig lower esophageal sphincter caused by cysteinyl leukotrienes, LTC4, LTD4 and LTE4, and the dihydroxy leukotriene, LTB4. We also measured LTD4-induced contraction inhibited by CysLT receptor antagonists, tetrodotoxin and atropine.ResultsIn the guinea pig lower esophageal sphincter strips, LTC4, LTD4 and LTE4, but not LTB4, caused concentration-dependent contractions. The relative potencies for cysteinyl leukotrienes to cause contraction were LTD4 = LTC4 > LTE4. LTE4 was a partial agonist. The LTD4-induced contraction was inhibited by two selective CysLT1 receptor antagonists, montelukast and zafirlukast, and by the dual CysLT1 and CysLT2 receptor antagonist BAY u9773. The combination of both montelukast and BAY u9773 did not potentiate the inhibition caused by montelukast alone. These findings indicate that CysLT1 mediates the contraction in the lower esophageal sphincter. Furthermore, LTD4-induced contraction was not affected by tetrodotoxin or atropine, suggesting a direct effect.ConclusionThese results demonstrate that cysteinyl leukotrienes, but not the dihydroxy leukotriene LTB4, cause contraction of the guinea pig lower esophageal sphincter. The CysLT1 receptor mediates this contraction