Phytochemicals as antibiotic alternatives to promote growth and enhance host health

There are heightened concerns globally on emerging drug-resistant superbugs and the lack of new antibiotics for treating human and animal diseases. For the agricultural industry, there is an urgent need to develop strategies to replace antibiotics for food-producing animals, especially poultry and livestock. The 2nd International Symposium on Alternatives to Antibiotics was held at the World Organization for Animal Health in Paris, France, December 12-15, 2016 to discuss recent scientific developments on strategic antibiotic-free management plans, to evaluate regional differences in policies regarding the reduction of antibiotics in animal agriculture and to develop antibiotic alternatives to combat the global increase in antibiotic resistance. More than 270 participants from academia, government research institutions, regulatory agencies, and private animal industries from >25 different countries came together to discuss recent research and promising novel technologies that could provide alternatives to antibiotics for use in animal health and production; assess challenges associated with their commercialization; and devise actionable strategies to facilitate the development of alternatives to antibiotic growth promoters (AGPs) without hampering animal production. The 3-day meeting consisted of four scientific sessions including vaccines, microbial products, phytochemicals, immune-related products, and innovative drugs, chemicals and enzymes, followed by the last session on regulation and funding. Each session was followed by an expert panel discussion that included industry representatives and session speakers. The session on phytochemicals included talks describing recent research achievements, with examples of successful agricultural use of various phytochemicals as antibiotic alternatives and their mode of action in major agricultural animals (poultry, swine and ruminants). Scientists from industry and academia and government research institutes shared their experience in developing and applying potential antibiotic-alternative phytochemicals commercially to reduce AGPs and to develop a sustainable animal production system in the absence of antibiotics.Fil: Lillehoj, Hyun. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Liu, Yanhong. University of California; Estados UnidosFil: Calsamiglia, Sergio. Universitat Autònoma de Barcelona; EspañaFil: Fernandez Miyakawa, Mariano Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; ArgentinaFil: Chi, Fang. Amlan International; Estados UnidosFil: Cravens, Ron L.. Amlan International; Estados UnidosFil: Oh, Sungtaek. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Gay, Cyril G.. United States Department of Agriculture. Agricultural Research Service; Argentin

Effect of nesiritide in patients with acute decompensated heart failure.

BACKGROUND: Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. METHODS: We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. RESULTS: Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P≤0.005 for both assessments or P≤0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.1 to 0.7; P=0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, -0.4 percentage points; 95% CI, -1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P=0.11). CONCLUSIONS: Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number, NCT00475852.

Effect of nesiritide in patients with acute decompensated heart failure

Background Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. Methods We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. Results Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P = 0.03) and 24 hours (68.2% vs. 66.1%, P = 0.007), but the prespecified level for significance (P≤0.005 for both assessments or P≤0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, −0.7 percentage points; 95% confidence interval [CI], −2.1 to 0.7; P = 0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, −0.4 percentage points; 95% CI, −1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P = 0.11). Conclusions Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number, NCT00475852.

Measurement of the Double-Differential Muon-neutrino Charged-Current Inclusive Cross Section in the NOvA Near Detector

We report cross-section measurements of the final-state muon kinematics for \numu charged-current interactions in the NOvA near detector using an accumulated 8.09$\times10^{20}$ protons-on-target (POT) in the NuMI beam. We present the results as a double-differential cross section in the observed outgoing muon energy and angle, as well as single-differential cross sections in the derived neutrino energy, $E_\nu$, and square of the four-momentum transfer, $Q^2$. We compare the results to inclusive cross-section predictions from various neutrino event generators via $\chi^2$ calculations using a covariance matrix that accounts for bin-to-bin correlations of systematic uncertainties. These comparisons show a clear discrepancy between the data and each of the tested predictions at forward muon angle and low $Q^2$, indicating a missing suppression of the cross section in current neutrino-nucleus scattering models

An Improved Measurement of Neutrino Oscillation Parameters by the NOvA Experiment

We present new $\nu_\mu\rightarrow\nu_e$, $\nu_\mu\rightarrow\nu_\mu$, $\overline{\nu}_\mu\rightarrow\overline{\nu}_e$, and $\overline{\nu}_\mu\rightarrow\overline{\nu}_\mu$ oscillation measurements by the NOvA experiment, with a 50% increase in neutrino-mode beam exposure over the previously reported results. The additional data, combined with previously published neutrino and antineutrino data, are all analyzed using improved techniques and simulations. A joint fit to the $\nu_e$, $\nu_\mu$, $\overline{\nu}_e$, and $\overline{\nu}_\mu$ candidate samples within the 3-flavor neutrino oscillation framework continues to yield a best-fit point in the normal mass ordering and the upper octant of the $\theta_{23}$ mixing angle, with $\Delta m^{2}_{32} = (2.41\pm0.07)\times 10^{-3}$ eV$^2$ and $\sin^2\theta_{23} = 0.57^{+0.03}_{-0.04}$. The data disfavor combinations of oscillation parameters that give rise to a large asymmetry in the rates of $\nu_e$ and $\overline{\nu}_e$ appearance. This includes values of the CP-violating phase in the vicinity of $\delta_\text{CP} = \pi/2$ which are excluded by $>3\sigma$ for the inverted mass ordering, and values around $\delta_\text{CP} = 3\pi/2$ in the normal ordering which are disfavored at 2$\sigma$ confidence.Comment: 11 pages, 6 figures. Supplementary material attached (7 figures

Extended search for supernova-like neutrinos in NOvA coincident with LIGO/Virgo detections

A search is performed for supernova-like neutrino interactions coincident with 76 gravitational wave events detected by the LIGO/Virgo Collaboration. For 40 of these events, full readout of the time around the gravitational wave is available from the NOvA Far Detector. For these events, we set limits on the fluence of the sum of all neutrino flavors of $F < 7(4)\times 10^{10}\mathrm{cm}^{-2}$ at 90% C.L. assuming energy and time distributions corresponding to the Garching supernova models with masses 9.6(27)$\mathrm{M}_\odot$. Under the hypothesis that any given gravitational wave event was caused by a supernova, this corresponds to a distance of $r > 29(50)$kpc at 90% C.L. Weaker limits are set for other gravitational wave events with partial Far Detector data and/or Near Detector data.Comment: 10 pages, 2 figure

Measurement of neutrino-induced neutral-current coherent π⁰ production in the NOvA near detector

The cross section of neutrino-induced neutral-current coherent π⁰ production on a carbon-dominated target is measured in the NOvA near detector. This measurement uses a narrow-band neutrino beam with an average neutrino energy of 2.7 GeV, which is of interest to ongoing and future long-baseline neutrino oscillation experiments. The measured, flux-averaged cross section is σ = 13.8±0.9(stat)±2.3(syst)×10⁻⁴⁰ cm²/nucleus, consistent with model prediction. This result is the most precise measurement of neutral-current coherent π⁰ production in the few-GeV neutrino energy region

Measurement of neutrino-induced neutral-current coherent π⁰ production in the NOvA near detector

The cross section of neutrino-induced neutral-current coherent π⁰ production on a carbon-dominated target is measured in the NOvA near detector. This measurement uses a narrow-band neutrino beam with an average neutrino energy of 2.7 GeV, which is of interest to ongoing and future long-baseline neutrino oscillation experiments. The measured, flux-averaged cross section is σ = 13.8±0.9(stat)±2.3(syst)×10⁻⁴⁰ cm²/nucleus, consistent with model prediction. This result is the most precise measurement of neutral-current coherent π⁰ production in the few-GeV neutrino energy region