Posaconazole as salvage treatment of invasive fungal infections in patients with underlying renal impairment.

OBJECTIVES: The aim of this study is to determine the efficacy and safety of posaconazole in patients with underlying renal impairment. Patients and methods We analysed the efficacy and safety of posaconazole in patients with renal impairment in a post hoc subanalysis of a Phase 3, multicentre, open-label trial in patients with invasive fungal infections (IFIs). In the Phase 3 study, 330 patients intolerant of or with IFIs refractory to standard antifungal therapy received posaconazole 800 mg daily in divided doses. In our subanalysis, 238 patients with proven/probable IFIs, including 65 patients with renal impairment (creatinine clearance < 50 mL/min or serum creatinine (sCR) level >2 mg/dL at baseline) and 173 patients with greater renal function [creatinine clearance >/= 50 mL/min (acceptable renal function)], formed the modified intent-to-treat population. Success was defined as complete or partial response, and non-success was defined as stable disease or treatment failure. RESULTS: Overall response rates were similar in the renal impairment group (49%) and in the acceptable renal function (50%) group. Seventeen of the 41 patients with renal impairment and aspergillosis responded. Adverse events occurred in 32/65 (49%) patients with renal impairment and in 72/173 (42%) patients with acceptable renal function. The most common adverse events in both groups were nausea (14% patients with renal impairment versus 8% with acceptable renal function), altered/elevated levels of other medications (8% versus 2%), increased sCR levels (6% versus 0%), vomiting (6% versus 4%), abdominal pain (5% versus 5%) and dizziness (5% versus 1%). CONCLUSIONS: These results suggest that posaconazole is effective and well tolerated in patients with refractory IFIs regardless of renal impairment.

Productive performance, meat quality and fatty acid profile of steers finished in confinement or supplemented at pasture.

Thirty Aberdeen Angus crossbred steers (281 ± 16 kg) were used to test the effect of finishing feeding system on growth performance, meat quality and fatty acid (FA) profile in intramuscular fat. Steers were fed in confinement (forage:concentrate ratio of 50 : 50; DM basis) or with different levels of energy supplementation (0, 0.4, 0.8 and 1.2% BW) at pasture (Avena strigosa Schreb and Lolium multiflorum L.). There were no differences between treatments for ADG (average=1.60 kg/day), hot carcass weight (HCW) (average=229 kg) and subcutaneous fat depth (average=3 mm). Dressing % (P=0.06; tendency) and carcass ADG (P=0.02) linearly increased with level of supplementation for pasture steers. No differences were observed between treatments for tenderness, marbling, pH, color b*, or cooking loss and drip loss in samples of Longissimus dorsi. However L* increased linearly (P=0.05) with level of supplementation. The concentrations of myristic, palmitic, estearic and linoleic FA did not differ among treatments. The concentration of n-3 FA increased (P<0.001) in steers at pasture compared with confinement, but n-6 FA concentrations did not differ between feeding system. Supplementation up to 0.4% BW increase (P<0.001) conjugated linoleic acid (CLA) and linolenic FA concentrations in intramuscular fat when compared with confinement. The level of supplementation on pasture linearly decreased (P<0.001) n-3 and CLA and linearly increased (P=0.001) the n-6 : n-3 ratio. Finishing of steers grazing winter pasture with energy supplementation or in confinement fed a medium-concentrate diet did not affect meat quality (tenderness, marbling, parameter b* on the CIE L*a*b* scale, cooking and drip losses) except for a* and L*. However, intramuscular fat of animals finished at pasture with moderate level of supplementation compared to animals fed in confinement had greater concentration of CLA, linolenic, and n-3, and lower n-6 : n-3 in intramuscular fat.

Neural networks for advanced control of robot manipulators.

Presents an approach and a systematic design methodology to adaptive motion control based on neural networks (NNs) for high-performance robot manipulators, for which stability conditions and performance evaluation are given. The neurocontroller includes a linear combination of a set of off-line trained NNs, and an update law of the linear combination coefficients to adjust robot dynamics and payload uncertain parameters. A procedure is presented to select the learning conditions for each NN in the bank. The proposed scheme, based on fixed NNs, is computationally more efficient than the case of using the learning capabilities of the neural network to be adapted, as that used in feedback architectures that need to propagate back control errors through the model to adjust the neurocontroller. A practical stability result for the neurocontrol system is given. That is, we prove that the control error converges asymptotically to a neighborhood of zero, whose size is evaluated and depends on the approximation error of the NN bank and the design parameters of the controller. In addition, a robust adaptive controller to NN learning errors is proposed, using a sign or saturation switching function in the control law, which leads to global asymptotic stability and zero convergence of control errors. Simulation results showing the practical feasibility and performance of the proposed approach to robotics are given.

Neural network-based model reference adaptive control system.

In this paper, an approach to model reference adaptive control based on neural networks is proposed and analyzed for a class of first-order continuous-time nonlinear dynamical systems. The controller structure can employ either a radial basis function network or a feedforward neural network to compensate adaptively the nonlinearities in the plant. A stable controller-parameter adjustment mechanism, which is determined using the Lyapunov theory, is constructed using a sigma-modification-type updating law. The evaluation of control error in terms of the neural network learning error is performed. That is, the control error converges asymptotically to a neighborhood of zero, whose size is evaluated and depends on the approximation error of the neural network. In the design and analysis of neural network-based control systems, it is important to take into account the neural network learning error and its influence on the control error of the plant. Simulation results showing the feasibility and performance of the proposed approach are given.

Encapsulated nitrate and cashew nut shell liquid on blood and rumen constituents, methane emission, and growth performance of lambs.

Nitrate can be a source of NPN for microbial growth at the same time that it reduces ruminal methane production. The objective of this study was to evaluate the effects of 2 encapsulated nitrate products used as urea replacers on blood and rumen constituents, methane emission, and growth performance of lambs. Eighteen Santa Inês male lambs (27 ± 4.9 kg) were individually allotted to indoor pens and assigned to a randomized complete block design with 6 blocks and 3 dietary treatments: control (CTL) = 1.5% urea, ENP = 4.51% encapsulated nitrate product (60.83% NO3(-) in the product DM), and ENP+CNSL = 4.51% ENP containing cashew nut shell liquid (60.83% NO3(-) and 2.96% cashew nut shell liquid [CNSL] in the product DM). Diets were isonitrogenous with 60:40 concentrate:forage (Tifton 85 hay) ratio. The experiment lasted for 92 d and consisted of 28 d for adaptation (a weekly 33% stepwise replacement of CTL concentrate by nitrate-containing concentrates) and 64 d for data collection. The ENP and ENP+CNSL showed greater (P < 0.05) red blood cell counts than CTL. Blood methemoglobin (MetHb) did not differ (P > 0.05) among treatments, with mean values within normal range and remaining below 1.1% of total hemoglobin. There was an increase (P < 0.05) in total short-chain fatty acids concentration at 3 h postfeeding for ENP, with an additional increase (P < 0.05) observed for ENP+CNSL. No treatment effects (P > 0.05) were observed on acetate to propionate ratio. Methane production (L/kg DMI) was reduced (P < 0.05) with nitrate inclusion, recording 28.6, 19.1, and 19.5 L/kg DMI for CTL, ENP, and ENP+CNSL, respectively. Addition of CNSL did not result (P > 0.05) in further reduction of methane production when compared with ENP. Final BW, DMI, ADG, and feed efficiency were similar (P > 0.05) among treatments. Values for DMI were 1.11, 1.03, and 1.04 kg/d and for ADG were 174, 154, and 158 g for CTL, ENP, and ENP+CNSL, respectively. In conclusion, encapsulated nitrate products showed no risks of toxicity based on MetHb formation. The products persistently reduced methane production without affecting performance. Inclusion of cashew nut shell liquid in the product formulation had no additional benefits on methane mitigation.

Relationships between chewing behavior, digestibility, and digesta passage kinetics in steers fed oat hay at restricted and ad libitum intakes.

The objective of this study was to evaluate the relationships between chewing behavior, digestibility, and digesta passage kinetics in steers fed oat hay at restricted and ad libitum intakes. Four Hereford steers, with an initial average BW of 136 kg, were used in an experiment conducted as a balanced 4 × 4 Latin square with 4 treatments (levels of intake) and 4 periods. Animals were fed lopsided oat hay (Avena strigosa Schreb.) at 4 levels of intake (as a percentage of BW): 1.5, 2.0, 2.5, and ad libitum. Digestibility, chewing behavior, and digesta passage kinetic measurements were recorded during the experimental period. Chewing rates during eating and ruminating [(chews•min(-1))/g of DMI•kg(-1) of BW•d(-1)] decreased (P = 0.018 and P = 0.032, respectively) with increased DMI (g•kg(-1) of BW•d(-1)), whereas total chewing and total time spent on each chewing activity increased. Calculated total energy expended by the chewing activity was 4.2, 4.4, 5.2, and 5.3% of ME intake for DMI of 1.5, 2.0, and 2.5% of BW and ad libitum, respectively, indicating that adjustments in animal chewing behavior may be a mechanism of reducing energy expenditure when forages are fed at restricted intake. Hay digestibility decreased (P < 0.001) with increased DMI (r = -0.865). Digesta mean retention time (h) was strongly correlated with DMI (r = -0.868) and OM digestibility (r = 0.844). At reduced intake, hay digestibility was enhanced (P < 0.001) by extending digesta retention time and by increasing chewing efficiency, highlighting the relationship between chewing behavior and the digestive process. Fractional outflow rate of particulate matter from the reticulorumen (k(1)) was positively correlated with total chews, emphasizing that the decrease in particle size caused by chewing facilitates particle flow through the digestive tract. Increased hay intake also increased (P < 0.001) k(1), whereas passage rate of the liquid phase, transit time, and rumen fill were not affected (P > 0.05). The latter was correlated with rumen volume (r = 0.803). In conclusion, the results of this study indicate that animals fed at restricted intake increased chewing rate when eating and ruminating, which, along with a longer digesta retention time, contributed to enhance feed digestibility.