High level of treatment failure with commonly used anthelmintics on Irish sheep farms

peer-reviewedBackground: In 2013 a Technology Adoption Program for sheep farmers was established to encourage the implementation of best management practices on sheep farms in Ireland. There were 4,500 participants in this programme in 2013. As part of this programme, farmers had the option to carry out a drench test to establish the efficacy of their anthelmintic treatment. Results: Flock faecal samples were collected before and after treatment administration and gastrointestinal nematode eggs enumerated. In total there were 1,893 participants in the task, however only 1,585 included both a pre- and post-treatment faecal sample. Of those, 1,308 provided information on the anthelmintic product that they used with 46%, 23% and 28% using a benzimidazole (BZ), levamisole (LEV) and macrocyclic lactone (ML) product respectively. The remaining farmers used a product inapplicable for inclusion in the task such as a flukicide or BZ/LEV combination product. Samples were included for analysis of drench efficacy if the pre-treatment flock egg count was ≥200 eggs per gram and the interval post-sampling was 10–14 days for BZ products, 4–7 days for LEV products and 14–18 days for ML products. These criteria reduced the number of valid tests to 369, 19.5% of all tests conducted. If the reduction post-treatment was ≥95% the treatment was considered effective. Only 51% of treatments were considered effective using this criterion. There was a significant difference in efficacy between the anthelmintic drug classes with BZ effective in only 30% of treatments, LEV effective in 52% of cases and ML effective in 76% of cases. Conclusions: Gastrointestinal nematode anthelmintic treatments, as practiced on Irish farms, have a high failure rate. There was a significant difference between the efficacies of the anthelmintic classes with BZ the least effective and ML the most effective

Quantitative basic residue requirements in the cleavage-activation site of the fusion glycoprotein as a determinant of virulence for Newcastle disease virus

Newcastle disease virus exhibits a wide range of pathogenicity and virulence which, as with all paramyxoviruses, is directly related to the cleavability of a precursor (F0) of the fusion glycoprotein by cellular proteases. Sequence analyses of the cleavage site of several virulent and avirulent isolates of the Newcastle disease virus serotype reveal a correlation between virulence or pathogenicity and a high content of basic amino acid residues at the cleavage site. A similar correlation has been seen for other paramyxoviruses

Oxytocin bolus versus oxytocin bolus and infusion for control of blood loss at elective caesarean section: double blind, placebo controlled, randomised trial

Objectives To determine the effects of adding an oxytocin infusion to bolus oxytocin on blood loss at elective caesarean section

REV-ERBα mediates complement expression and diurnal regulation of microglial synaptic phagocytosis

The circadian clock regulates various aspects of brain health including microglial and astrocyte activation. Here, we report that deletion of the master clock protein BMAL1 in mice robustly increases expression of complement genes, includin

Sources and pathways of glacial meltwater in the Bellingshausen Sea, Antarctica

Meltwater content and pathways determine the impact of Antarctica's melting ice shelves on ocean circulation and climate. Using ocean glider observations, we quantify meltwater distribution and transport within the Bellingshausen Sea's Belgica Trough. Meltwater is present at different densities and with different turbidities: both are indicative of a layer's ice shelf of origin. To investigate how ice-shelf origin separates meltwater into different export pathways, we compare these observations with high-resolution tracer-release model simulations. Meltwater filaments branch off the Antarctic Coastal Current into the southwestern trough. Meltwater also enters the Belgica Trough in the northwest via an extended western pathway, hence the greater observed southward (0.50 mSv) than northward (0.17 mSv) meltwater transport. Together, the observations and simulations reveal meltwater retention within a cyclonic in-trough gyre, which has the potential to promote climactically important feedbacks on circulation and future melting

Blockade of Interferon Beta, but Not Interferon Alpha, Signaling Controls Persistent Viral Infection

SummaryAlthough type I interferon (IFN-I) is thought to be beneficial against microbial infections, persistent viral infections are characterized by high interferon signatures suggesting that IFN-I signaling may promote disease pathogenesis. During persistent lymphocytic choriomeningitis virus (LCMV) infection, IFNα and IFNβ are highly induced early after infection, and blocking IFN-I receptor (IFNAR) signaling promotes virus clearance. We assessed the specific roles of IFNβ versus IFNα in controlling LCMV infection. While blockade of IFNβ alone does not alter early viral dissemination, it is important in determining lymphoid structure, lymphocyte migration, and anti-viral T cell responses that lead to accelerated virus clearance, approximating what occurs during attenuation of IFNAR signaling. Comparatively, blockade of IFNα was not associated with improved viral control, but with early dissemination of virus. Thus, despite their use of the same receptor, IFNβ and IFNα have unique and distinguishable biologic functions, with IFNβ being mainly responsible for promoting viral persistence

Kinematic Analysis of a Protostellar Multiple System: Measuring the Protostar Masses and Assessing Gravitational Instability in the Disks of L1448 IRS3B and L1448 IRS3A

We present new Atacama Large Millimeter/submillimeter Array (ALMA) observations towards a compact (230~au separation) triple protostar system, L1448 IRS3B, at 879~\micron with \contbeam~resolution. Spiral arm structure within the circum-multiple disk is well resolved in dust continuum toward IRS3B, and we detect the known wide (2300~au) companion, IRS3A, also resolving possible spiral substructure. Using dense gas tracers, C17O, H13CO$+$, and H13CN, we resolve the Keplerian rotation for both the circum-triple disk in IRS3B and the disk around IRS3A. Furthermore, we use the molecular line kinematic data and radiative transfer modeling of the molecular line emission to confirm that the disks are in Keplerian rotation with fitted masses of $1.19^{+0.13}_{-0.07}$ for IRS3B-ab, $1.51^{+0.06}_{-0.07}$~Msun for IRS3A, and place an upper limit on the central protostar mass for the tertiary IRS3B-c of 0.2~Msun. We measure the mass of the fragmenting disk of IRS3B to be 0.29~Msun from the dust continuum emission of the circum-multiple disk and estimate the mass of the clump surrounding IRS3B-c to be 0.07~Msun. We also find that the disk around IRS3A has a mass of 0.04~Msun. By analyzing the Toomre~Q parameter, we find the IRS3A circumstellar disk is gravitationally stable (Q$>$5), while the IRS3B disk is consistent with a gravitationally unstable disk (Q$<$1) between the radii 200-500~au. This coincides with the location of the spiral arms and the tertiary companion IRS3B-c, supporting the hypothesis that IRS3B-c was formed in situ via fragmentation of a gravitationally unstable disk