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The phase 2, open-label ACCORDION (ClinicalTrials.gov: NCT02349048) study investigated the efficacy, safety and pharmacokinetics of a 6-or 8-week regimen of simeprevir, daclatasvir and sofosbuvir in treatment-naïve patients with chronic hepatitis C virus (HCV) genotype (GT) 1 infection and either early-stage fibrosis or compensated cirrhosis. Patients were assigned to treatment groups according to their fibrosis stage. Early-stage fibrosis: simeprevir 150 mg, daclatasvir 60 mg, sofosbuvir 400 mg once daily for 6 weeks; compensated cirrhosis: same regimen for 8 weeks. The primary endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). Safety, tolerability and pharmacokinetics of simeprevir, daclatasvir and sofosbuvir were investigated. Sixty-eight patients were treated (6-week group: n = 59; 8-week group: n = 9). SVR12 was achieved by 86.4% (51/59) of patients with early-stage fibrosis and by 100% (9/9) of patients with cirrhosis. The main reason for not achieving SVR12 in the 6-week group was viral relapse (11.9%; 7/59). One patient had on-treatment failure due to an early withdrawal (lost to follow-up due to incarceration). One patient with SVR12 in the 6-week group had a late viral relapse at post-treatment week 24. No clinically significant drug-drug interactions were observed. Adverse events were reported in 63.2% of patients (43/68) and were mainly grade 1/2. None of these led to treatment discontinuation. The 3 direct-acting antiviral regimens of simeprevir, daclatasvir and sofosbuvir were safe and well tolerated in treatment-naïve, HCV GT1-infected patients with early-stage fibrosis or compensated cirrhosis. [ABSTRACT FROM AUTHOR]

Dairy slurry is used commonly as an animal-sourced fertilizer in agronomic production. However, residual effects of slurry application on intake and digestibility of alfalfa (Medicago sativa L.) silage from subsequent harvests are not well known. The objective of this study was to determine if moisture concentration of alfalfa silage and timing of dairy slurry application relative to subsequent harvest affected intake and digestibility by sheep. Katahdin crossbred ewes (n = 18; 48 ± 5.3 kg) in mid-gestation were stratified by BW and allocated randomly in each of two periods to one of six treatments arranged in a two x three factorial arrangement. Treatments consisted of recommended (RM; 46.8%) or low (LM; 39.7%) moisture at baling after either no slurry application (NS), slurry application to stubble immediately after removal of the previous cutting (S0), or slurry application 14 d after removal of the previous cutting (S14). Silages were chopped through a commercial straw chopper, packed into plastic trash cans, and then offered to ewes within 4 d of chopping. Period 1 of the intake and digestion study consisted of a 14-d adaptation followed by a 7-d fecal collection period. Period 2 followed period 1 after a 4-d rest and consisted of an 11-d adaptation followed by 7 d of fecal collection. Ewes were housed individually in 1.4 x 4.3-m pens equipped with rubber mat flooring. Feces were swept from the floor twice daily, weighed, and dried at 50 °C. Ewes had ad libitum access to water and were offered chopped silage for a minimum of 10% refusal (DM). Blood samples were collected immediately prior to feeding, and 4 and 8 h after feeding on the day prior to the end of each period. Organic matter intake (g/kg BW) and OM digestibility tended (P < 0.10) to be, and digestible OM intake (g/kg BW) was reduced by slurry application. Lymphocytes (% of total white blood cells) were greater (P < 0.05) from LM vs. RM and from NS vs. S0 and S14. Red blood cell concentrations were greater (P < 0.05) from S14 vs. S0 and from S0 and S14 vs. NS. Serum urea N concentrations did not differ (P > 0.17) across treatments. Therefore, moisture concentration of alfalfa silage within the range used in this study may not affect voluntary intake or digestibility, but slurry application may have an effect on digestible OM intake. Also, moisture concentration of alfalfa silage and time of dairy slurry application may affect specific blood hemograms. [ABSTRACT FROM AUTHOR]

Ionophores and antibiotics have been shown to decrease ruminal methanogenesis both in vitro and in vivo but have shown little evidence toward a sustainable means of mitigation. Feed additive rotation was proposed and investigated for methane, VFA, and microbial population response. In the present study, cannulated steers (n = 12) were fed a moderateforage basal diet in a Calan gate facility for 13 wk. In addition to the basal diet, steers were randomly assigned to 1 of 6 treatments: 1) control, no additive; 2) bambermycin, 20 mg bambermycin/d; 3) monensin, 200 mg monensin/d; 4) the basal diet + weekly rotation of bambermycin and monensin treatments (B7M); 5) the basal diet + rotation of bambermycin and monensin treatments every 14 d (B14M); and 6) the basal diet + rotation of bambermycin and monensin treatments every 21 d (B21M). Steers were blocked by weight in a randomized complete block design where the week was the repeated measure. Rumen fluid was collected weekly for analysis (n = 13), and results were normalized according to individual OM intake (OMI; kg/d). Potential activity of methane production was not significantly different among treatments (P > 0.05). However, treatment tended to affect the CH4-to-propionate ratio (P = 0.0565), which was highest in the control and lowest in the monensin, B21M, and B14M treatments (0.42 vs. 0.36, 0.36, and 0.33, respectively). The CH4:propionate ratio was lowest in wk 2 and 3 (P < 0.05) but the ratio in wk 4 to 12 was not different from the ratio in wk 0. Week also affected total VFA, with total VFA peaking at wk 3 and plummeting at wk 4 (4.02 vs. 2.86 mM/kg OMI; P < 0.05). A significant treatment × week interaction was observed for the acetate-to-propionate (A:P) ratio, where bambermycin- and rotationally fed steers did not have a reduced A:P ratio compared with monensin-fed steers throughout the feeding period (P < 0.0001). Microbial analysis revealed significant shifts, but several predominant classes showed adaptation between 4 and 6 wk after additive initiation. There was no significant evidence to suggest that rotations of monensin and bambermycin provided additional benefits to steers consuming a moderate-forage diet at the microbial/animal and environmental level versus those continuously fed. [ABSTRACT FROM AUTHOR]

Coproduct feedstuffs offer a unique and potentially profitable avenue for cattle feeding strategies. However, research is lacking in the evaluation of varying coproducts on ruminal fermentation and digestive characteristics when included as the major component of the diet of cows. Our objective was to determine the effect of coproduct feedstuffs as a forage replacement on digestive and fermentative characteristics of cows. Eight ruminally fistulated cows (672 ± 32.0 kg initial BW and approximately 9 yr of age) were stratified by BW and randomly allocated to 1 of 4 diets (2 cows.diet-1.period-1) in a 2-period study: soybean hulls (SH), distillers' dried grains with solubles (DG), an isoenergetic mixture of soybean hulls and distillers' dried grains with solubles (MX), or ad libitum hay plus 0.9 kg/d of an isoenergetic mixture of soybean hulls and distillers' dried grains with solubles (HY). Diets were formulated to meet the ME requirements of a similar, companion study. Coproduct amounts were increased over a 14-d period. This was followed by a 14-d adaptation to diet and facilities and 5 d of total fecal collections. On the final day of fecal collections, rumen fluid was sampled immediately prior to feeding and 2, 4, 6, 8, 10 and 12 h after feeding for measurement of rumen VFA and ammonia concentrations. Intake of DM and OM was not different (P ≥ 0.28) among treatments, but digestibilities of DM, OM, NDF, and ADF were improved (P < 0.05) by coproduct feeding and by MX vs. the mean of SH and DG. Ruminal DM and OM fill were greater (P < 0.05) for cows offered HY than for cows offered the coproduct diets, greater for cows offered SH than for cows offered DG, and for the mean of SH and DG vs. MX. Ruminal retention time was greater (P < 0.05) for HY vs. the coproduct diets and for SH vs. DG. Apparent N absorption tended (P < 0.10) to be greater for cows offered the coproduct diets than for cows offered HY and greater for cows offered DG than for cows offered SH. Total VFA averaged across sampling times were greatest (P < 0.05) for cows offered SH, and ruminal ammonia N was greatest (P < 0.05) for cows offered either DG or MX at all sampling times. Based on these data, coproduct feedstuffs may be fed to meet the energy requirement of cows without negative effects on digestion or ruminal fermentation. [ABSTRACT FROM AUTHOR]

Forestland area estimates are the first principle of most ecological assessments across spatial scales. The definition of forest used by the United Nations Food and Agriculture Organization is based on a 10 per cent canopy cover threshold while the definition of forest used by the US Forest Service Forest Inventory and Analysis programme in western woodlands is based on a 5 per cent canopy cover threshold. Most of the eastern US forests have the ability to reach 10 per cent cover; however, in semi-arid areas such as western Texas, there is considerable area of forestland with less than 10 per cent canopy cover. The main objective of this research was to provide an estimate of forestland area in west Texas based on a 10 per cent canopy cover threshold. To accomplish this, we developed and compared three classification models that discriminate between inventory plots with less than 10 per cent cover and those with at least 10 per cent cover. We found that ∼3.9 million ha (17 per cent) of forestland area (based on 5 per cent cover) did not meet the 10 per cent canopy cover threshold. [ABSTRACT FROM PUBLISHER]

We have recently shown that an exogenous gradient of interleukin-8 (IL-8) induces the transendothelial migration of neutrophils. Treatment of endothelium with the cytokines IL-1 or tumor necrosis factor (TNF) also causes neutrophil transmigration, and recent evidence suggests that this may be due to endogenous IL-8 produced by the endothelium. We have used specific chemotactic desensitization of neutrophils to investigate the role of IL-8 in transmigration through cytokine-activated endothelium. Preincubation of neutrophils with IL-8 reduced their chemotactic transmigration response to an IL-8 gradient by 81%, demonstrating desensitization. Transmigration in response to cytokine-activated endothelium was inhibited by 104% after IL-8 preincubation, thus tending to support the role of IL-8. However, preincubation with another neutrophil chemotactic factor N-formyl-methionyl-leucyl-phenylalanine (FMLP), which did not affect the IL-8 response, also inhibited transmigration, by 74%. This suggests that FMLP preincubation acts to inhibit a non-IL-8-dependent mechanism of transmigration through cytokine-activated endothelium. Chemotactic factor pretreatment of neutrophils did not reduce their adhesion to activated endothelium, but specifically blocked the transmigration step. We have therefore shown that chemotactic transmigration can be subjected to factor-specific desensitization, and have used this to provide evidence supporting a role for IL-8 in transmigration through cytokine-activated endothelium, as well as suggesting a further IL-8-independent mechanism. These data also provide a mechanism for the observed defect in accumulation of neutrophils at inflammatory sites when chemotactic factors are infused intravenously. [ABSTRACT FROM AUTHOR]