Fluoroquinolone treatment of experimental Salmonella enterica serovar Typhimurium DT104 infections in chickens selects for both gyrA mutations and changes in efflux pump gene expression

Objectives: To determine the efficacy of enrofloxacin (Baytril) in chickens in eradicating three different resistance phenotypes of Salmonella enterica and to examine the resistance mechanisms of resulting mutants. Methods: In two separate replicate experiments (I and 11), three strains of Salmonella enterica serovar Typhimurium DT104 [strain A, fully antibiotic-sensitive strain; strain B, isogenic multiple antibiotic-resistant (MAR) derivative of A; strain C, veterinary penta-resistant phenotype strain containing GyrA Phe-83], were inoculated into day-old chicks at similar to 10(3) Cfu/bird. At day 10, groups of chicks (n =10) were given either enrofloxacin at 50 ppm in their drinking water for 5 days or water alone (control). Caecal contents were monitored for presence of Salmonella and colonies were replica plated to media containing antibiotics or overlaid with cyclohexane to determine the proportion of isolates with reduced susceptibility. The MICs of antibiotics and cyclohexane tolerance were determined for selected isolates from the chicks. Mutations in topoisomerase genes were examined by DHPLC and expression of marA, soxS, acrB, acrD and acrF by RT-PCR. Results: In experiment 1, but not 11, enrofloxacin significantly reduced the numbers of strain A compared with the untreated control group. In experiment 11, but not 1, enrofloxacin significantly reduced the numbers of strain B. Shedding of strain C was unaffected by enrofloxacin treatment. Birds infected with strains A and B gave rise to isolates with decreased fluoroquinolone susceptibility. Isolates derived from strain A or B requiring > 128 mg/L nalidixic acid for inhibition contained GyrA Asn-82 or Phe-83. Isolates inhibited by 16 mg/L nalidixic acid were also less susceptible to antibiotics of other chemical classes and became cyclohexane-tolerant (e.g. MAR). Conclusions: These studies demonstrate that recommended enrofloxacin treatment of chicks rapidly selects for strains with reduced fluoroquinolone susceptibility from fully sensitive and MAR strains. It can also select for MAR isolates.

A life less ordinary: The ritualization of the domestic sphere in later prehistoric Europe

This article, which is based on the fourteenth McDonald Lecture, considers two tensions in contemporary archaeology. one is between interpretations of specific structures, monuments and deposits as the result of either 'ritual' 'practical' activities in the past, and the other is between an archaeology that focuses on subsistence and adaptation and one that emphasizes cognition, meaning, and agency. It suggests that these tensions arise from an inadequate conception of ritual itself. Drawing on recent studies of ritualization, it suggests that it might be more helpful to consider how aspects of domestic life took on special qualities in later prehistoric Europe. The discussion is based mainly on Neolithic enclosures and other monuments, Bronze Age and Iron Age settlement sites and the Viereckschanzen of central Europe. it may have implications for field archaeology as well as social archaeology, and also for those who study the formation of the archaeological record.

Less-is-more effects without the recognition heuristic

Inferences consistent with “recognition-based” decision-making may be drawn for various reasons other than recognition alone. We demonstrate that, for 2-alternative forced-choice decision tasks, less-is-more effects (reduced performance with additional learning) are not restricted to recognition-based inference but can also be seen in circumstances where inference is knowledge-based but item knowledge is limited. One reason why such effects may not be observed more widely is the dependence of the effect on specific values for the validity of recognition and knowledge cues. We show that both recognition and knowledge validity may vary as a function of the number of items recognized. The implications of these findings for the special nature of recognition information, and for the investigation of recognition-based inference, are discussed

Milling performance of north European hull-less barleys and characterization of resultant millstreams

Four hull-less barley samples were milled on a Buhler MLU 202 laboratory mill and individual and combined milling fractions were characterized. The best milling performance was obtained when the samples were conditioned to 14.3% moisture. Yields were 37-48% for straight-run flour, 47-56% for shorts, and 5-8% for bran. The beta-glucan contents of the straight-run white flours were 1.6-2.1%, of which approximate to49% was water-extractable. The arabinoxylan contents were 1.2-1.5%, of which approximate to17% was water-extractable. Shorts and bran fractions contained more beta-glucan (4.2-5.8% and 3.0-4.7%, respectively) and arabinoxylan (6.1-7.7% and 8.1-11.8%, respectively) than the white flours. For those fractions, beta-glucan extractability was high (58.5 and 52.3%, respectively), whereas arabinoxylan extractability was very low (approximate to6.5 and 2.0%, respectively). The straight-run white flours had low alpha-amylase, beta-glucanase, and endoxylanase activities. The highest alpha-amylase activity was found in the shorts fractions and the highest beta-glucanase and endoxylanase activities were generally found in the bran fractions. Endoxylanase inhibitor activities were low in the white flours and highest in the shorts fractions. High flavanoid, tocopherol, and tocotrienol contents were found in bran and shorts fractions.

Less-is-more effects in knowledge-based heuristic inference

Inference on the basis of recognition alone is assumed to occur prior to accessing further information (Pachur & Hertwig, 2006). A counterintuitive result of this is the “less-is-more” effect: a drop in the accuracy with which choices are made as to which of two or more items scores highest on a given criterion as more items are learned (Frosch, Beaman & McCloy, 2007; Goldstein & Gigerenzer, 2002). In this paper, we show that less-is-more effects are not unique to recognition-based inference but can also be observed with a knowledge-based strategy provided two assumptions, limited information and differential access, are met. The LINDA model which embodies these assumptions is presented. Analysis of the less-is-more effects predicted by LINDA and by recognition-driven inference shows that these occur for similar reasons and casts doubt upon the “special” nature of recognition-based inference. Suggestions are made for empirical tests to compare knowledge-based and recognition-based less-is-more effects

Hydrogen-bond assisted stabilization of the less favored conformation of a tridentate Schiff base ligand in dinuclear nickel(II) complex: an experimental and theoretical study

The Schiff base ligand, HL (2-[1-(3-methylamino-propylimino)-ethyl]-phenol), the 1:1 condensation product of 2-hydroxy acetophenone and N-methyl-1,3-diaminopropane, has been synthesized and characterized by X-ray crystallography as the perchlorate salt [H2L]ClO4 (1). The structure consists of discrete [H2L](+) cations and perchlorate anions. Two dinuclear Ni-II complexes, [Ni2L2(NO2)(2)] (2), [Ni2L2(NO3)(2)] (3) have been synthesized using this ligand and characterized by single crystal X-ray analyses. Complexes 2 and 3 are centrosymmetric dimers in which the Ni-II ions are in distorted fac- and mer-octahedral environments, respectively, bridged by two mu(2)-phenolate ions of deprotonated ligand, L. The plane of the phenyl rings and the Ni2O2 basal plane are nearly coplanar in 2 but almost perpendicular in 3. We have studied and explained this different behavior using high level DFT calculations (RI-BP86/def2-TZVP level of theory). The conformation observed in 3, which is energetically less favorable, is stabilized via intermolecular non-covalent interactions. Under the excitation of ultraviolet light, characteristic fluorescence of compound 1 was observed; by comparison fluorescence intensity decreases in case of compound 3 and completely quenched in compound 2.

PINCER trial: a cluster randomised trial comparing the effectiveness and cost-effectiveness of a pharmacist-led IT-based intervention with simple feedback in reducing rates of clinically important errors in medicines management in general practices

Background: Medication errors in general practice are an important source of potentially preventable morbidity and mortality. Building on previous descriptive, qualitative and pilot work, we sought to investigate the effectiveness, cost-effectiveness and likely generalisability of a complex pharm acist-led IT-based intervention aiming to improve prescribing safety in general practice. Objectives: We sought to: • Test the hypothesis that a pharmacist-led IT-based complex intervention using educational outreach and practical support is more effective than simple feedback in reducing the proportion of patients at risk from errors in prescribing and medicines management in general practice. • Conduct an economic evaluation of the cost per error avoided, from the perspective of the National Health Service (NHS). • Analyse data recorded by pharmacists, summarising the proportions of patients judged to be at clinical risk, the actions recommended by pharmacists, and actions completed in the practices. • Explore the views and experiences of healthcare professionals and NHS managers concerning the intervention; investigate potential explanations for the observed effects, and inform decisions on the future roll-out of the pharmacist-led intervention • Examine secular trends in the outcome measures of interest allowing for informal comparison between trial practices and practices that did not participate in the trial contributing to the QRESEARCH database. Methods Two-arm cluster randomised controlled trial of 72 English general practices with embedded economic analysis and longitudinal descriptive and qualitative analysis. Informal comparison of the trial findings with a national descriptive study investigating secular trends undertaken using data from practices contributing to the QRESEARCH database. The main outcomes of interest were prescribing errors and medication monitoring errors at six- and 12-months following the intervention. Results: Participants in the pharmacist intervention arm practices were significantly less likely to have been prescribed a non-selective NSAID without a proton pump inhibitor (PPI) if they had a history of peptic ulcer (OR 0.58, 95%CI 0.38, 0.89), to have been prescribed a beta-blocker if they had asthma (OR 0.73, 95% CI 0.58, 0.91) or (in those aged 75 years and older) to have been prescribed an ACE inhibitor or diuretic without a measurement of urea and electrolytes in the last 15 months (OR 0.51, 95% CI 0.34, 0.78). The economic analysis suggests that the PINCER pharmacist intervention has 95% probability of being cost effective if the decision-maker’s ceiling willingness to pay reaches £75 (6 months) or £85 (12 months) per error avoided. The intervention addressed an issue that was important to professionals and their teams and was delivered in a way that was acceptable to practices with minimum disruption of normal work processes. Comparison of the trial findings with changes seen in QRESEARCH practices indicated that any reductions achieved in the simple feedback arm were likely, in the main, to have been related to secular trends rather than the intervention. Conclusions Compared with simple feedback, the pharmacist-led intervention resulted in reductions in proportions of patients at risk of prescribing and monitoring errors for the primary outcome measures and the composite secondary outcome measures at six-months and (with the exception of the NSAID/peptic ulcer outcome measure) 12-months post-intervention. The intervention is acceptable to pharmacists and practices, and is likely to be seen as costeffective by decision makers.

Impact Assessment in the EU: a tool for better regulation, less regulation or less bad regulation?

Impact Assessments (IAs) were introduced at the EU level under the rhetorical facade of ‘better regulation’. The actual aim was to improve not only the quality but also the reputation of EU regulation before stakeholders. However, evidence brought forward by a number of evaluations pointed out that IAs are yet to achieve acceptable quality standards. The paper offers an overview of different disciplinary approaches for looking at IAs. It suggests that risk regulation encompasses the theoretical foundations to help understand the role of IAs in the EU decisionmaking process. The analysis of 60 early days preliminary IAs provides empirical evidence regarding policy alternatives, methodology of consultation and use of quantitative techniques. Findings suggest that dawn period IAs were used mainly to provide some empirical evidence for regulatory intervention in front of stakeholders. The paper concludes with assumptions about the future role of IAs at EU level.

Discrete demand side control performance under dynamic building simulation: a heat pump application

This study presents the findings of applying a Discrete Demand Side Control (DDSC) approach to the space heating of two case study buildings. High and low tolerance scenarios are implemented on the space heating controller to assess the impact of DDSC upon buildings with different thermal capacitances, light-weight and heavy-weight construction. Space heating is provided by an electric heat pump powered from a wind turbine, with a back-up electrical network connection in the event of insufficient wind being available when a demand occurs. Findings highlight that thermal comfort is maintained within an acceptable range while the DDSC controller maintains the demand/supply balance. Whilst it is noted that energy demand increases slightly, as this is mostly supplied from the wind turbine, this is of little significance and hence a reduction in operating costs and carbon emissions is still attained.

Suitability of pesticide risk indicators for less developed countries: a comparison

Pesticide risk indicators provide simple support in the assessment of environmental and health risks from pesticide use, and can therefore inform policies to foster a sustainable interaction of agriculture with the environment. For their relative simplicity, indicators may be particularly useful under conditions of limited data availability and resources, such as in Less Developed Countries (LDCs). However, indicator complexity can vary significantly, in particular between those that rely on an exposure–toxicity ratio (ETR) and those that do not. In addition, pesticide risk indicators are usually developed for Western contexts, which might cause incorrect estimation in LDCs. This study investigated the appropriateness of seven pesticide risk indicators for use in LDCs, with reference to smallholding agriculture in Colombia. Seven farm-level indicators, among which 3 relied on an ETR (POCER, EPRIP, PIRI) and 4 on a non-ETR approach (EIQ, PestScreen, OHRI, Dosemeci et al., 2002), were calculated and then compared by means of the Spearman rank correlation test. Indicators were also compared with respect to key indicator characteristics, i.e. user friendliness and ability to represent the system under study. The comparison of the indicators in terms of the total environmental risk suggests that the indicators not relying on an ETR approach cannot be used as a reliable proxy for more complex, i.e. ETR, indicators. ETR indicators, when user-friendly, show a comparative advantage over non-ETR in best combining the need for a relatively simple tool to be used in contexts of limited data availability and resources, and for a reliable estimation of environmental risk. Non-ETR indicators remain useful and accessible tools to discriminate between different pesticides prior to application. Concerning the human health risk, simple algorithms seem more appropriate for assessing human health risk in LDCs. However, further research on health risk indicators and their validation under LDC conditions is needed.

Technological change and the challenges for regional development: building social capital in less-favoured regions

The relevance of regional policy for less favoured regions (LFRs) reveals itself when policy-makers must reconcile competitiveness with social cohesion through the adaptation of competition or innovation policies. The vast literature in this area generally builds on an overarching concept of ‘social capital’ as the necessary relational infrastructure for collective action diversification and policy integration, in a context much influenced by a dynamic of industrial change and a necessary balance between the creation and diffusion of ‘knowledge’ through learning. This relational infrastructure or ‘social capital’ is centred on people’s willingness to cooperate and ‘envision’ futures as a result of “social organization, such as networks, norms and trust that facilitate action and cooperation for mutual benefit” (Putnam, 1993: 35). Advocates of this interpretation of ‘social capital’ have adopted the ‘new growth’ thinking behind ‘systems of innovation’ and ‘competence building’, arguing that networks have the potential to make both public administration and markets more effective as well as ‘learning’ trajectories more inclusive of the development of society as a whole. This essay aims to better understand the role of ‘social capital’ in the production and reproduction of uneven regional development patterns, and to critically assess the limits of a ‘systems concept’ and an institution-centred approach to comparative studies of regional innovation. These aims are discussed in light of the following two assertions: i) learning behaviour, from an economic point of view, has its determinants, and ii) the positive economic outcomes of ‘social capital’ cannot be taken as a given. It is suggested that an agent-centred approach to comparative research best addresses the ‘learning’ determinants and the consequences of social networks on regional development patterns. A brief discussion of the current debate on innovation surveys has been provided to illustrate this point.