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

Fundamental limitations for quantum and nano thermodynamics

The relationship between thermodynamics and statistical physics is valid in the thermodynamic limit - when the number of particles becomes very large. Here, we study thermodynamics in the opposite regime - at both the nano scale, and when quantum effects become important. Applying results from quantum information theory we construct a theory of thermodynamics in these limits. We derive general criteria for thermodynamical state transformations, and as special cases, find two free energies: one that quantifies the deterministically extractable work from a small system in contact with a heat bath, and the other that quantifies the reverse process. We find that there are fundamental limitations on work extraction from nonequilibrium states, owing to finite size effects and quantum coherences. This implies that thermodynamical transitions are generically irreversible at this scale. As one application of these methods, we analyse the efficiency of small heat engines and find that they are irreversible during the adiabatic stages of the cycle.Comment: Final, published versio

Techniques for temporal detection of neural sensitivity to external stimulation

We propose a simple measure of neural sensitivity for characterizing stimulus coding. Sensitivity is defined as the fraction of neurons that show positive responses to n stimuli out of a total of N. To determine a positive response, we propose two methods: Fisherian statistical testing and a data-driven Bayesian approach to determine the response probability of a neuron. The latter is non-parametric, data-driven, and captures a lower bound for the probability of neural responses to sensory stimulation. Both methods are compared with a standard test that assumes normal probability distributions. We applied the sensitivity estimation based on the proposed method to experimental data recorded from the mushroom body (MB) of locusts. We show that there is a broad range of sensitivity that the MB response sweeps during odor stimulation. The neurons are initially tuned to specific odors, but tend to demonstrate a generalist behavior towards the end of the stimulus period, meaning that the emphasis shifts from discrimination to feature learning

The dark and bright sides of hubris: Conceptual implications for leadership and governance research.

Hubris among corporate leaders has recently gained much academic attention, with strategy and corporate governance research focusing mainly on negative aspects, such as overreach by strategic leaders during acquisitions. However, adjacent disciplines including entrepreneurship and innovation identify positive consequences too. How comparable are these findings? Appraising the conceptual and methodological approaches, we find that while the hubris concept has many strengths, several challenges remain. We suggest conceptual and empirical research directions aimed at increasing construct clarity, validating the hubris construct, and extending the scope of hubris research. We also propose that research with boards and top management teams can help clarify how they make decisions to cope with the “dark side” of hubris without suppressing “bright side” outcomes

Ensemble approach to predict specificity determinants: benchmarking and validation

<p>Abstract</p> <p>Background</p> <p>It is extremely important and challenging to identify the sites that are responsible for functional specification or diversification in protein families. In this study, a rigorous comparative benchmarking protocol was employed to provide a reliable evaluation of methods which predict the specificity determining sites. Subsequently, three best performing methods were applied to identify new potential specificity determining sites through ensemble approach and common agreement of their prediction results.</p> <p>Results</p> <p>It was shown that the analysis of structural characteristics of predicted specificity determining sites might provide the means to validate their prediction accuracy. For example, we found that for smaller distances it holds true that the more reliable the prediction method is, the closer predicted specificity determining sites are to each other and to the ligand.</p> <p>Conclusion</p> <p>We observed certain similarities of structural features between predicted and actual subsites which might point to their functional relevance. We speculate that majority of the identified potential specificity determining sites might be indirectly involved in specific interactions and could be ideal target for mutagenesis experiments.</p

Antisense DNA parameters derived from next-nearest-neighbor analysis of experimental data

<p>Abstract</p> <p>Background</p> <p>The enumeration of tetrameric and other sequence motifs that are positively or negatively correlated with <it>in vivo </it>antisense DNA effects has been a useful addition to the arsenal of information needed to predict effective targets for antisense DNA control of gene expression. Such retrospective information derived from <it>in vivo </it>cellular experiments characterizes aspects of the sequence dependence of antisense inhibition that are not predicted by nearest-neighbor (NN) thermodynamic parameters derived from <it>in vitro </it>experiments. However, quantitation of the antisense contributions of motifs is problematic, since individual motifs are not isolated from the effects of neighboring nucleotides, and motifs may be overlapping. These problems are circumvented by a next-nearest-neighbor (NNN) analysis of antisense DNA effects in which the overlapping nature of nearest-neighbors is taken into account.</p> <p>Results</p> <p>Next-nearest-neighbor triplet combinations of nucleotides are the simplest that include overlapping sequence effects and therefore can encompass interactions beyond those of nearest neighbors. We used singular value decomposition (SVD) to fit experimental data from our laboratory in which phosphorothioate-modified antisense DNAs (S-DNAs) 20 nucleotides long were used to inhibit cellular protein expression in 112 experiments involving four gene targets and two cell lines. Data were fitted using a NNN model, neglecting end effects, to derive NNN inhibition parameters that could be combined to give parameters for a set of 49 sequences that represents the inhibitory effects of all possible overlapping triplet interactions in the cellular targets of these antisense S-DNAs. We also show that parameters to describe subsets of the data, such as the mRNAs being targeted and the cell lines used, can be included in such a derivation. While NNN triplet parameters provided an adequate model to fit our data, NN doublet parameters did not.</p> <p>Conclusions</p> <p>The methodology presented illustrates how NNN antisense inhibitory information can be derived from <it>in vivo </it>cellular experiments. Subsequent calculations of the antisense inhibitory parameters for any mRNA target sequence automatically take into account the effects of all possible overlapping combinations of nearest-neighbors in the sequence. This procedure is more robust than the tallying of tetrameric motifs that have positive or negative antisense effects. The specific parameters derived in this work are limited in their applicability by the relatively small database of experiments that was used in their derivation.</p

RNA Oxidation Adducts 8-OHG and 8-OHA Change with Aβ42 Levels in Late-Stage Alzheimer's Disease

While research supports amyloid-β (Aβ) as the etiologic agent of Alzheimer's disease (AD), the mechanism of action remains unclear. Evidence indicates that adducts of RNA caused by oxidation also represent an early phenomenon in AD. It is currently unknown what type of influence these two observations have on each other, if any. We quantified five RNA adducts by gas chromatography/mass spectroscopy across five brain regions from AD cases and age-matched controls. We then used a reductive directed analysis to compare the RNA adducts to common indices of AD neuropathology and various pools of Aβ. Using data from four disease-affected brain regions (Brodmann's Area 9, hippocampus, inferior parietal lobule, and the superior and middle temporal gyri), we found that the RNA adduct 8-hydroxyguanine (8-OHG) decreased, while 8-hydroxyadenine (8-OHA) increased in AD. The cerebellum, which is generally spared in AD, did not show disease related changes, and no RNA adducts correlated with the number of plaques or tangles. Multiple regression analysis revealed that SDS-soluble Aβ42 was the best predictor of changes in 8-OHG, while formic acid-soluble Aβ42 was the best predictor of changes in 8-OHA. This study indicates that although there is a connection between AD related neuropathology and RNA oxidation, this relationship is not straightforward

Noninvasive assessment of asthma severity using pulse oximeter plethysmograph estimate of pulsus paradoxus physiology

<p>Abstract</p> <p>Background</p> <p>Pulsus paradoxus estimated by dynamic change in area under the oximeter plethysmograph waveform (PEP) might provide a measure of acute asthma severity. Our primary objective was to determine how well PEP correlates with forced expiratory volume in 1-second (%FEV₁) (criterion validity) and change of %FEV₁(responsiveness) during treatment in pediatric patients with acute asthma exacerbations.</p> <p>Methods</p> <p>We prospectively studied subjects 5 to 17 years of age with asthma exacerbations. PEP, %FEV₁, airway resistance and accessory muscle use were recorded at baseline and at 2 and 4 hours after initiation of corticosteroid and bronchodilator treatments. Statistical associations were tested with Pearson or Spearman rank correlations, logistic regression using generalized estimating equations, or Wilcoxon rank sum tests.</p> <p>Results</p> <p>We studied 219 subjects (median age 9 years; male 62%; African-American 56%). Correlation of PEP with %FEV₁demonstrated criterion validity (r = - 0.44, 95% confidence interval [CI], - 0.56 to - 0.30) and responsiveness at 2 hours (r = - 0.31, 95% CI, - 0.50 to - 0.09) and 4 hours (r = - 0.38, 95% CI, - 0.62 to - 0.07). PEP also correlated with airway resistance at baseline (r = 0.28 for ages 5 to 10; r = 0.45 for ages 10 to 17), but not with change over time. PEP was associated with accessory muscle use (OR 1.16, 95% CI, 1.11 to 1.21, P < 0.0001).</p> <p>Conclusions</p> <p>PEP demonstrates criterion validity and responsiveness in correlations with %FEV₁. PEP correlates with airway resistance at baseline and is associated with accessory muscle use at baseline and at 2 and 4 hours after initiation of treatment. Incorporation of this technology into contemporary pulse oximeters may provide clinicians improved parameters with which to make clinical assessments of asthma severity and response to treatment, particularly in patients who cannot perform spirometry because of young age or severity of illness. It might also allow for earlier recognition and improved management of other disorders leading to elevated pulsus paradoxus.</p

Interacting effects of soil fertility and atmospheric CO 2 on leaf area growth and carbon gain physiology in Populus × euramericana (Dode) Guinier

Two important processes which may limit productivity gains in forest ecosystems with rising atmospheric CO 2 are reduction in photosynthetic capacity following prolonged exposure to high CO 2 and diminution of positive growth responses when soil nutrients, particularly N, are limiting. To examine the interacting effects of soil fertility and CO 2 enrichment on photosynthesis and growth in trees we grew hybrid poplar ( Populus × euramericana ) for 158 d in the field at ambient and twice ambient CO 2 and in soil with low or high N availability. We measured the timing and rate of canopy development, the seasonal dynamics of leaf level photosynthetic capacity, respiration, and N and carbohydrate concentration, and final above- and belowground dry weight. Single leaf net CO 2 assimilation (A) increased at elevated CO 2 over the majority of the growing season in both fertility treatments. At high fertility, the maximum size of individual leaves, total leaf number, and seasonal leaf area duration (LAD) also increased at elevated CO 2 , leading to a 49% increase in total dry weight. In contrast, at low fertility leaf area growth was unaffected by CO 2 treatment. Total dry weight nonetheless increased 25% due to CO 2 effects on A. Photosynthetic capacity (A at constant internal p(CO 2 ), (( C 1 )) was reduced in high CO 2 plants after 100 d growth at low fertility and 135 d growth at high fertility. Analysis of A responses to changing C 1 indicated that this negative adjustment of photosynthesis was due to a reduction in the maximum rate of CO 2 fixation by Rubisco. Maximum rate of electron transport and phosphate regeneration capacity were either unaffected or declined at elevated CO 2 . Carbon dioxide effects on leaf respiration were most pronounced at high fertility, with increased respiration mid-season and no change (area basis) or reduced (mass basis) respiration late-season in elevated compared to ambient CO 2 plants. This temporal variation correlated with changes in leaf N concentration and leaf mass per area. Our results demonstrate the importance of considering both structural and physiological pathways of net C gain in predicting tree responses to rising CO 2 under conditions of suboptimal soil fertility.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65655/1/j.1469-8137.1995.tb04295.x.pd