Development of an Antimicrobial Stewardship Intervention Using a Model of Actionable Feedback

We describe the development of an audit and feedback intervention to improve antibiotic prescribing in the neonatal intensive care unit (NICU) using a theoretical framework. Participants included attending physicians, neonatal fellows, pediatric residents, and nurse practitioners. The intervention was based on the “model of actionable feedback” which emphasizes that feedback should be timely, individualized, nonpunitive, and customized to be effective. We found that real-time feedback could not be provided for the parameters established in this study, as we had to collect and analyze numerous data elements to assess appropriate initiation and continuation of antibiotics and required longer intervals to examine trends in antibiotic use. We learned during focus groups that NICU clinicians strongly resisted assigning individual responsibility for antibiotic prescribing as they viewed this as a shared responsibility informed by each patient's laboratory data and clinical course. We were able to create a non-punitive atmosphere thanks to written informed consent from NICU attendings and assurance from leadership that prescribing practices would not be used to assess job performance. We provided customized, meaningful feedback integrating input from the participants. Adapting the principles of the “model of actionable feedback” to provide feedback for antimicrobial prescribing practices proved challenging in the NICU setting

High-Throughput Screening for Small-Molecule Inhibitors of LARG-Stimulated RhoA Nucleotide Binding via a Novel Fluorescence Polarization Assay

Guanine nucleotide-exchange factors (GEFs) stimulate guanine nucleotide exchange and the subsequent activation of Rho-family proteins in response to extracellular stimuli acting upon cytokine, tyrosine kinase, adhesion, integrin, and G-protein coupled receptors (GPCRs). Upon Rho activation, several downstream events occur, such as morphological and cytokskeletal changes, motility, growth, survival, and gene transcription. The RhoGEF Leukemia-Associated RhoGEF (LARG) is a member of the Regulators of G-protein Signaling Homology Domain (RH) family of GEFs originally identified as a result of chromosomal translocation in acute myeloid leukemia. Using a novel fluorescence polarization guanine nucleotide binding assay utilizing BODIPY-Texas Red-GTPγS (BODIPY-TR-GTPγS), we performed a ten-thousand compound high-throughput screen for inhibitors of LARG-stimulated RhoA nucleotide binding. Five compounds identified from the high-throughput screen were confirmed in a non-fluorescent radioactive guanine nucleotide binding assay measuring LARG-stimulated [35S] GTPγS binding to RhoA, thus ruling out non-specific fluorescent effects. All five compounds selectively inhibited LARG-stimulated RhoA [35S] GTPγS binding, but had little to no effect upon RhoA or Gαo [35S] GTPγS binding. Therefore, these five compounds should serve as promising starting points for the development of small molecule inhibitors of LARG-mediated nucleotide exchange as both pharmacological tools and therapeutics. In addition, the fluorescence polarization guanine nucleotide binding assay described here should serve as a useful approach for both high-throughput screening and general biological applications

Applying consumer responsibility principle in evaluating environmental load of carbon emissions

There is a need for a proper indicator in order to assess the environmental impact of international trade, therefore using the carbon footprint as an indicator can be relevant and useful. The aim of this study is to show from a methodological perspective how the carbon footprint, combined with input- output models can be used for analysing the impacts of international trade on the sustainable use of national resources in a country. The use of the input-output approach has the essential advantage of being able to track the transformation of goods through the economy. The study examines the environmental impact of consumption related to international trade, using the consumer responsibility principle. In this study the use of the carbon footprint and input-output methodology is shown on the example of the Hungarian consumption and the impact of international trade. Moving from a production- based approach in climate policy to a consumption-perspective principle and allocation, would also help to increase the efficiency of emission reduction targets and the evaluation of the ecological impacts of international trade

The liver pharmacological and xenobiotic gene response repertoire

We have used a supervised classification approach to systematically mine a large microarray database derived from livers of compound-treated rats. Thirty-four distinct signatures (classifiers) for pharmacological and toxicological end points can be identified. Just 200 genes are sufficient to classify these end points. Signatures were enriched in xenobiotic and immune response genes and contain un-annotated genes, indicating that not all key genes in the liver xenobiotic responses have been characterized. Many signatures with equal classification capabilities but with no gene in common can be derived for the same phenotypic end point. The analysis of the union of all genes present in these signatures can reveal the underlying biology of that end point as illustrated here using liver fibrosis signatures. Our approach using the whole genome and a diverse set of compounds allows a comprehensive view of most pharmacological and toxicological questions and is applicable to other situations such as disease and development

Multiple carbon accounting to support just and effective climate policies

Negotiating reductions in greenhouse gas emission involves the allocation of emissions and of emission reductions to specific agents, and notably, within the current UN framework, to associated countries. As production takes place in supply chains,increasingly extending over several countries, there are various options available in which emissions originating from one and the same activity may be attributed to different agents along the supply chain and thus to different countries. In this way, several distinct types of national carbon accounts can be constructed. We argue that these accounts will typically differ in the information they provide to individual countries on the effects their actions have on global emissions; and they may also, to varying degrees, prove useful in supporting the pursuit of an effective and just climate policy. None of the accounting systems, however, prove 'best' in achieving these aims under real-world circumstances; we thus suggest compiling reliable data to aid in the consistent calculation of multiple carbon accounts on a global level

Spectrophotometric determination of chromium as the chromium-peroxo-4-(2-pyridylazo)resorcinol complex

Der ternäre Chrom-Peroxo-PAR-Komplex weist einen scheinbaren molaren Extinktionskoeffizienten von 6280 l · mol −1 · cm −1 auf, wenn er aus 0,1 M schwefelsaurer Lösung mit Ethylacetat extrahiert wird. Das Beersche Gesetz wird bis zu 6,0 μg Cr/ml befolgt. Die Bedingungen für eine optimale Farbbildung, die Zusammensetzung des Komplexes, die Wirkung verschiedener Begleitionen und die Anwendung auf Stähle werden beschrieben. The ternary complex chromium-peroxo-PAR exhibits an apparent molar absorptivity of 6280 l mol −1 cm −1 when extracted into ethyl acetate from 0.1 M sulfuric acid solution. Beer's law is followed for solutions containing up to 6.0 μg Cr ml −1 . Conditions for optimum color formation, complex composition, effects of diverse ions, and application to the determination of chromium in steels are described.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46457/1/216_2004_Article_BF00480608.pd