Effect of pH and level of concentrate in the diet on the production of biohydrogenation intermediates in a dual-flow continuous culture

Milk fat depression in cows fed high-grain diets has been related to an increase in the concentration of trans-10 C-18:1 and trans-10, cis-12 conjugated linoleic acid (CLA) in milk. These fatty acids (FA) are produced as a result of the alteration in rumen biohydrogenation of dietary unsaturated FA. Because a reduction in ruminal pH is usually observed when high-concentrate diets are fed, the main cause that determines the alteration in the biohydrogenation pathways is not clear. The effect of pH (6.4 vs. 5.6) and dietary forage to concentrate ratios (F:C; 70:30 F:C vs. 30:70 F:C) on rumen microbial fermentation, effluent FA profile, and DNA concentration of bacteria involved in lipolysis and biohydrogenation processes were investigated in a continuous culture trial. The dual-flow continuous culture consisted of 2 periods of 8 d (5 d for adaptation and 3 d for sampling), with a 2 x 2 factorial arrangement of treatments. Samples from solid and liquid mixed effluents were taken for determination of total N, ammonia-N, and volatile fatty acid concentrations, and the remainder of the sample was lyophilized. Dry samples were analyzed for dry matter, ash, neutral and acid detergent fiber, FA, and purine contents. The pH 5.6 reduced organic matter and fiber digestibility, ammonia-N concentration and flow, and crude protein degradation, and increased nonammonia and dietary N flows. The pH 5.6 decreased the flow of C-18:0, trans-11 C-18:1 and cis-9, trans-11 CLA, and increased the flow of trans-10 C-18:1, C18:2n-6, C18:3n-3, trans-11, cis-15 C-18:2 and trans-10, cis-12 CLA in the 1 h after feeding effluent. The pH 5.6 reduced Anaerovibrio lipolytica (32.7 vs. 72.1 pg/10 ng of total DNA) and Butyrivibrio fibrisolvens vaccenic acid subgroup (588 vs. 1,394 pg/10 ng of total DNA) DNA concentrations. The high-concentrate diet increased organic matter and fiber digestibility, nonammonia and bacterial N flows, and reduced ammonia-N concentration and flow. The high-concentrate diet reduced trans-11 C-18:1 and trans-10 C-18:1, and increased C18:2n-6, C18:3n-3 and trans-10, cis-12 CLA proportions in the 1 h after feeding effluent. The increase observed in trans-10, cis-12 CLA proportion in the 1 h after feeding effluent due to the high-concentrate diet was smaller that that observed at pH 5.6. Results indicate that the pH is the main cause of the accumulation of trans-10 C-18:1 and trans-10, cis-12 CLA in the effluent, but the trans-10, cis-12 CLA proportion can be also affected by high levels of concentrate in the diet

Diffusive epidemic process: theory and simulation

We study the continuous absorbing-state phase transition in the one-dimensional diffusive epidemic process via mean-field theory and Monte Carlo simulation. In this model, particles of two species (A and B) hop on a lattice and undergo reactions B -> A and A + B -> 2B; the total particle number is conserved. We formulate the model as a continuous-time Markov process described by a master equation. A phase transition between the (absorbing) B-free state and an active state is observed as the parameters (reaction and diffusion rates, and total particle density) are varied. Mean-field theory reveals a surprising, nonmonotonic dependence of the critical recovery rate on the diffusion rate of B particles. A computational realization of the process that is faithful to the transition rates defining the model is devised, allowing for direct comparison with theory. Using the quasi-stationary simulation method we determine the order parameter and the survival time in systems of up to 4000 sites. Due to strong finite-size effects, the results converge only for large system sizes. We find no evidence for a discontinuous transition. Our results are consistent with the existence of three distinct universality classes, depending on whether A particles diffusive more rapidly, less rapidly, or at the same rate as B particles.Comment: 19 pages, 5 figure

Could Reduced Fluid Intake Cause the Placebo Effect Seen in Overactive Bladder Clinical Trials? Analysis of a Large Solifenacin Integrated Database

Objective To assess the hypothesis that patients receiving placebo in overactive bladder (OAB) trials who experience less benefit from “treatment” continue with behavioral modifications such as fluid restriction, whereas those on active treatment adopt more normal drinking patterns. This may manifest itself as a reduction in micturition frequency (MF). Materials and Methods We interrogated a large integrated database containing pooled patient data from 4 randomized, placebo-controlled phase III OAB solifenacin studies. A statistical correction was applied to MF to remove the influence of fluid intake. Results Pooled analysis using patient-level data from 3011 patients and accounting for the studies within the models showed that all patients voided progressively less total urine per 24 hours during treatment than at baseline. However, reduction in total urine volume voided per 24 hours was larger in patients receiving placebo vs those on solifenacin; with a substantial decrease in 24-hour urine output in the placebo group from baseline to week 4, which was not the case in active groups. After correcting MF for volume voided for each patient using the statistical correction and averaging the corrected MF per treatment arm, the placebo effect almost disappeared. Patients on solifenacin voided less often, with a statistically significant increase in volume voided each time they voided, vs placebo. Conclusion Assuming volume voided is a good surrogate measure for fluid intake, this analysis shows that fluid restriction almost completely explains the reduction in MF in the placebo group. In contrast, patients receiving active treatment adopt more normal drinking patterns once they start to perceive improvement in their OAB symptoms