Understanding the culture of antimicrobial prescribing in agriculture: a qualitative study of UK pig veterinary surgeons

Objectives The use of antimicrobials in food-producing animals has been linked with the emergence of antimicrobial resistance in bacterial populations, with consequences for animal and public health. This study explored the underpinning drivers, motivators and reasoning behind prescribing decisions made by veterinary surgeons working in the UK pig industry. Methods A qualitative interview study was conducted with 21 veterinary surgeons purposively selected from all UK pig veterinary surgeons. Thematic analysis was used to analyse transcripts. Results Ensuring optimum pig health and welfare was described as a driver for antimicrobial use by many veterinary surgeons and was considered a professional and moral obligation. Veterinary surgeons also exhibited a strong sense of social responsibility over the need to ensure that antimicrobial use was responsible. A close relationship between management practices, health and economics was evident, with improvements in management commonly identified as being potential routes to reduce antimicrobial usage; however, these were not always considered economically viable. The relationship with clients was identified as being a source of professional stress for practitioners due to pressure from farmers requesting antimicrobial prescriptions, and concern over poor compliance of antimicrobial administration by some farmers. Conclusions The drivers behind prescribing decisions by veterinary surgeons were complex and diverse. A combination of education, improving communication between veterinary surgeons and farmers, and changes in regulations, in farm management and in consumer/retailer demands may all be needed to ensure that antimicrobial prescribing is optimal and to achieve significant reductions in use

Aspirin, clopidogrel and prasugrel monotherapy in patients with type 2 diabetes mellitus: a double-blind randomised controlled trial of the effects on thrombotic markers and microRNA levels

Background: Despite increased atherothrombotic risk in type 2 diabetes mellitus, (T2DM) the best preventative antithrombotic strategy remains undetermined. We defined the effects of three antiplatelet agents on functional readout and biomarker kinetics in platelet activation and coagulation in patients with T2DM. Materials and methods: 56 patients with T2DM were randomised to antiplatelet monotherapy with aspirin 75 mg once daily (OD), clopidogrel 75 mg OD or prasugrel 10 mg OD during three periods of a crossover study. Platelet aggregation (PA) was determined by light-transmittance aggregometry and P-selectin expression by flow cytometry. Markers of fibrin clot dynamics, inflammation and coagulation were measured. Plasma levels of 14 miRNA were assessed by quantitative polymerase chain reactions. Results: Of the 56 patients, 24 (43%) were receiving aspirin for primary prevention of ischaemic events and 32 (57%) for secondary prevention. Prasugrel was the strongest inhibitor of ADP-induced PA (mean ± SD maximum response to 20μmol/L ADP 77.6 ± 8.4% [aspirin] vs. 57.7 ± 17.6% [clopidogrel] vs. 34.1 ± 14.1% [prasugrel], p < 0.001), P-selectin expression (30 μmol/L ADP; 45.1 ± 21.4% vs. 27.1 ± 19.0% vs. 14.1 ± 14.9%, p < 0.001) and collagen-induced PA (2 μg/mL; 62.1 ± 19.4% vs. 72.3 ± 18.2% vs. 60.2 ± 18.5%, p < 0.001). Fibrin clot dynamics and levels of coagulation and inflammatory proteins were similar. Lower levels of miR-24 (p = 0.004), miR-191 (p = 0.019), miR-197 (p = 0.009) and miR-223 (p = 0.014) were demonstrated during prasugrel-therapy vs. aspirin. Circulating miR-197 was lower in those cardiovascular disease during therapy with aspirin (p = 0.039) or prasugrel (p = 0.0083). Conclusions: Prasugrel monotherapy in T2DM provided potent platelet inhibition and reduced levels of a number of platelet-associated miRNAs. miR-197 is a potential marker of cardiovascular disease in this population. Clinical outcome studies investigating prasugrel monotherapy are warranted in individuals with T2DM. Trial registration: EudraCT, 2009-011907-22. Registered 15 March 2010, https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-011907-22/GB

Localization of tenascin in human skin wounds

A total of 56 surgically treated human skin wounds with a wound age between 8h and 7 months were investigated. Tenascin was visualized by immunohistochemistry and appeared first in the wound area pericellularly around fibroblastic cells approximately 2 days after wounding. A network-like interstitial positive staining pattern was first detectable in 3-day-old skin wounds. In all wounds with an age of 5 days or more, intensive reactivity for tenascin could be observed in the lesional area (dermal-epidermal junction, wound edge, areas of bleeding). In wounds with an age of more than approximately 1.5 months no positive staining occurred in the scar tissue. In conclusion, for forensic purposes, positive staining for tenascin restricted to the pericellular area of fibroblastic cells indicates a wound age of at least 2 days. Network-like structures appear after approximately 3 days or more. Since tenascin seems to be regularly detectable in skin wounds older than 5 days, the lack of a positive reaction in a sufficient number of specimens indicates a wound age of less than 5 days. The lack of a positive reaction in the granulation tissue of wounds with advanced wound age indicates a survival time of more than about 1.5 months, but a positive staining in older wounds cannot be excluded

Closing the Mind's Eye: Incoming Luminance Signals Disrupt Visual Imagery

Mental imagery has been associated with many cognitive functions, both high and low-level. Despite recent scientific advances, the contextual and environmental conditions that most affect the mechanisms of visual imagery remain unclear. It has been previously shown that the greater the level of background luminance the weaker the effect of imagery on subsequent perception. However, in these experiments it was unclear whether the luminance was affecting imagery generation or storage of a memory trace. Here, we report that background luminance can attenuate both mental imagery generation and imagery storage during an unrelated cognitive task. However, imagery generation was more sensitive to the degree of luminance. In addition, we show that these findings were not due to differential dark adaptation. These results suggest that afferent visual signals can interfere with both the formation and priming-memory effects associated with visual imagery. It follows that background luminance may be a valuable tool for investigating imagery and its role in various cognitive and sensory processes

Topological dissection of the membrane transport protein Mhp1 derived from cysteine accessibility and mass spectrometry

Cys accessibility and quantitative intact mass spectrometry (MS) analyses have been devised to study the topological transitions of Mhp1, the membrane protein for sodium-linked transport of hydantoins from Microbacterium liquefaciens. Mhp1 has been crystallised in three forms (outward-facing open, outward-facing occluded with substrate bound, and inward-facing open). We show that one natural cysteine residue, Cys327, out of three, has an enhanced solvent accessibility in the inward-facing (relative to the outward-facing) form. Reaction of the purified protein, in detergent, with the thiol-reactive N-ethylmalemide (NEM), results in modification of Cys327, suggesting that Mhp1 adopts predominantly inward-facing conformations. Addition of either sodium ions or the substrate 5-benzyl-L-hydantoin (L-BH) does not shift this conformational equilibrium, but, systematic co-addition of the two results in an attenuation of labelling, indicating a shift toward outward-facing conformations that can be interpreted using conventional enzyme kinetic analyses. Such measurements can afford the Km for each ligand as well as the stoichiometry of ion-substrate coupled conformational changes. Mutations that perturb the substrate binding site either result in the protein being unable to adopt outward-facing conformations or in a global destabilisation of structure. The methodology combines covalent labeling, mass spectrometry and kinetic analyses in a straightforward workflow applicable to a range of systems, enabling the interrogation of changes in a protein’s conformation required for function at varied concentrations of substrates, and the consequences of mutations on these conformational transitions

The impact of Cenozoic cooling on assemblage diversity in planktonic foraminifera

© 2016 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited. The attached file is the published version of the article

The Far-Infrared Properties of Spatially Resolved AKARI Observations

We present the spatially resolved observations of IRAS sources from the Japanese infrared astronomy satellite AKARI All-Sky Survey during the performance verification (PV) phase of the mission. We extracted reliable point sources matched with IRAS point source catalogue. By comparing IRAS and AKARI fluxes, we found that the flux measurements of some IRAS sources could have been over or underestimated and affected by the local background rather than the global background. We also found possible candidates for new AKARI sources and confirmed that AKARI observations resolved IRAS sources into multiple sources. All-Sky Survey observations are expected to verify the accuracies of IRAS flux measurements and to find new extragalactic point sources.Comment: 11 pages, 7 figures, accepted publication in PASJ AKARI special issu

How large should whales be?

The evolution and distribution of species body sizes for terrestrial mammals is well-explained by a macroevolutionary tradeoff between short-term selective advantages and long-term extinction risks from increased species body size, unfolding above the 2g minimum size induced by thermoregulation in air. Here, we consider whether this same tradeoff, formalized as a constrained convection-reaction-diffusion system, can also explain the sizes of fully aquatic mammals, which have not previously been considered. By replacing the terrestrial minimum with a pelagic one, at roughly 7000g, the terrestrial mammal tradeoff model accurately predicts, with no tunable parameters, the observed body masses of all extant cetacean species, including the 175,000,000g Blue Whale. This strong agreement between theory and data suggests that a universal macroevolutionary tradeoff governs body size evolution for all mammals, regardless of their habitat. The dramatic sizes of cetaceans can thus be attributed mainly to the increased convective heat loss is water, which shifts the species size distribution upward and pushes its right tail into ranges inaccessible to terrestrial mammals. Under this macroevolutionary tradeoff, the largest expected species occurs where the rate at which smaller-bodied species move up into large-bodied niches approximately equals the rate at which extinction removes them.Comment: 7 pages, 3 figures, 2 data table

Body mass index, estimated glucose disposal rate and vascular complications in type 1 diabetes: Beyond glycated haemoglobin

Aims To understand the relationship between insulin resistance (IR), assessed as estimated glucose disposal rate (eGDR), and microvascular/macrovascular complications in people with type 1 diabetes. Materials and methods Individuals with a confirmed diagnosis of type 1 diabetes were included in this cross-sectional study. BMI was categorised into normal weight (18.0–24.9 kg m−2), overweight (25.0–29.9 kg m−2) and obese groups (≥30.0 kg m−2). We categorised eGDR into four groups: eGDR >8, 6–7.9, 4–5.9 and <4 mg kg−1 min−1. Multiple logistic regression was used to identify associations with vascular complications, after adjusting for relevant confounders. Results A total of 2151 individuals with type 1 diabetes were studied. Median [interquartile range (IQR)] age was 41.0 [29.0, 55.0] with diabetes duration of 20.0 [11, 31] years. Odds ratio (OR) for retinopathy and nephropathy in obese compared with normal weight individuals was 1.64 (95% CI: 1.24–2.19; p = 0.001) and 1.62 (95% CI: 1.10–2.39; p = 0.015), while the association with cardiovascular disease just failed to reach statistical significance (OR 1.66 [95% CI: 0.97–2.86; p = 0.066]). Comparing individuals with eGDR ≥8 mg kg−1 min−1 and <4 mg kg−1 min−1 showed OR for retinopathy, nephropathy and macrovascular disease of 4.84 (95% CI: 3.36–6.97; p < 0.001), 8.35 (95% CI: 4.86–14.34; p < 0.001) and 13.22 (95% CI: 3.10–56.38; p < 0.001), respectively. Individuals with the highest eGDR category (≥8 mg kg−1 min−1) had the lowest complication rates irrespective of HbA1c levels. Conclusions Obesity is prevalent in type 1 diabetes and diabetes complications are not only related to glucose control. IR, assessed as eGDR, is strongly associated with both microvascular and macrovascular complications, regardless of HbA1c levels

Fluoromycobacteriophages for rapid, specific, and sensitive antibiotic susceptibility testing of Mycobacterium tuberculosis

Rapid antibiotic susceptibility testing of Mycobacterium tuberculosis is of paramount importance as multiple- and extensively- drug resistant strains of M. tuberculosis emerge and spread. We describe here a virus-based assay in which fluoromycobacteriophages are used to deliver a GFP or ZsYellow fluorescent marker gene to M. tuberculosis, which can then be monitored by fluorescent detection approaches including fluorescent microscopy and flow cytometry. Pre-clinical evaluations show that addition of either Rifampicin or Streptomycin at the time of phage addition obliterates fluorescence in susceptible cells but not in isogenic resistant bacteria enabling drug sensitivity determination in less than 24 hours. Detection requires no substrate addition, fewer than 100 cells can be identified, and resistant bacteria can be detected within mixed populations. Fluorescence withstands fixation by paraformaldehyde providing enhanced biosafety for testing MDR-TB and XDR-TB infections. © 2009 Piuri et al