Effect of Different Media on the Bactericidal Activity of Colistin and on the Synergistic Combination With Azidothymidine Against mcr-1-Positive Colistin-Resistant Escherichia coli

Antimicrobial susceptibility testing (AST) performed according to defined guidelines is important to identify resistance and to predict the clinical success or failure of specific antibiotic therapy. However, these guidelines do not cover all physiological conditions that can have a tremendous impact on in vivo resistance. In this study, we tested the susceptibility of thirteen mcr-1-positive Escherichia coli strains against colistin, one of the last resort antibiotics for treating multi-drug resistant pathogens, in media recommended for ASTs as well as – physiologically more relevant – in human serum and artificial urine (AU). Minimal inhibitory concentration (MIC) values in heat-inactivated human serum were similar to those in cation-adjusted Mueller-Hinton broth (CAMHB), but reduced in native serum for almost all strains that could grow in this media. In AU MIC values for mcr-1 positive E. coli were increased significantly up to 16-fold compared to that in CAMBH, which did not apply to the colistin-susceptible E. coli strains tested. Although different growth media could affect the MIC of colistin alone, their impact on the synergistic effect of the combination with the antiviral drug azidothymidine was minimal. The higher divalent cation concentration combined with acidic pH values is most likely responsible for the increased MIC values of the mcr-1 harboring E. coli strains tested against colistin in AU compared to that in CAMHB. Antimicrobial susceptibility screening procedures for colistin using CAMHB only could lead to an underestimation of resistance under different physiological conditions. Therefore, not only pharmacokinetic but also pharmacodynamic studies in urine are as important as in serum or plasma

Robust Multi-Image HDR Reconstruction for the Modulo Camera

Photographing scenes with high dynamic range (HDR) poses great challenges to consumer cameras with their limited sensor bit depth. To address this, Zhao et al. recently proposed a novel sensor concept - the modulo camera - which captures the least significant bits of the recorded scene instead of going into saturation. Similar to conventional pipelines, HDR images can be reconstructed from multiple exposures, but significantly fewer images are needed than with a typical saturating sensor. While the concept is appealing, we show that the original reconstruction approach assumes noise-free measurements and quickly breaks down otherwise. To address this, we propose a novel reconstruction algorithm that is robust to image noise and produces significantly fewer artifacts. We theoretically analyze correctness as well as limitations, and show that our approach significantly outperforms the baseline on real data.Comment: to appear at the 39th German Conference on Pattern Recognition (GCPR) 201

Two different network topologies yield bistability in models of mesoderm and anterior mesendoderm specification in amphibians

AbstractUnderstanding the Gene Regulatory Networks (GRNs) that underlie development is a major question for systems biology. The establishment of the germ layers is amongst the earliest events of development and has been characterised in numerous model systems. The establishment of the mesoderm is best characterised in the frog Xenopus laevis and has been well studied both experimentally and mathematically. However, the Xenopus network has significant differences from that in mouse and humans, including the presence of multiple copies of two key genes in the network, Mix and Nodal. The axolotl, a urodele amphibian, provides a model with all the benefits of amphibian embryology but crucially only a single Mix and Nodal gene required for the specification of the mesoderm. Remarkably, the number of genes within the network is not the only difference. The interaction between Mix and Brachyury, two transcription factors involved in the establishment of the endoderm and mesoderm respectively, is not conserved. While Mix represses Brachyury in Xenopus, it activates Brachyury in axolotl. Thus, whilst the topology of the networks in the two species differs, both are able to form mesoderm and endoderm in vivo. Based on current knowledge of the structure of the mesendoderm GRN we develop deterministic models that describe the time evolution of transcription factors in a single axolotl cell and compare numerical simulations with previous results from Xenopus. The models are shown to have stable steady states corresponding to mesoderm and anterior mesendoderm, with the in vitro model showing how the concentration of Activin can determine cell fate, while the in vivo model shows that β-catenin concentration can determine cell fate. Moreover, our analysis suggests that additional components must be important in the axolotl network in the specification of the full range of tissues

Development of Sequence Tagged Microsatellite Site (STMS) markers in Azalea

A genomic library was constructed from DNA of two azalea genotypes: a Belgian pot azalea R. simsii hybrid Mevr. Van Belle and a Chinese R. simsii from Daoxian. An enrichment of microsatellite containing sequences was performed as in Van de Wiel et al. (1999). Fragments were sequenced and primers were designed that allow the amplification of the microsatellite repeat. About 220 microsatellite containing clones were selected from the enrichment procedure. Mainly dinucleotide repeats and some trinucleotide repeats were found. The selected primers were tested in a small set of reference varieties to check their value (specificity and polymorphic rate) and to set up the PCR-conditions. Five primer pairs have been tested, two of them gave a specific and polymorphic pattern. They were further screened by radioactive PCR on a selection of 5 plants from the azalea breeders gene pool which included the two genotypes used library construction. These 2 STMS markers uniquely identified the 5 plants

Construction and Measurements of an Improved Vacuum-Swing-Adsorption Radon-Mitigation System

In order to reduce backgrounds from radon-daughter plate-out onto detector surfaces, an ultra-low-radon cleanroom is being commissioned at the South Dakota School of Mines and Technology. An improved vacuum-swing-adsorption radon mitigation system and cleanroom build upon a previous design implemented at Syracuse University that achieved radon levels of $\sim$0.2$\,$Bq$\,$m$^{-3}$. This improved system will employ a better pump and larger carbon beds feeding a redesigned cleanroom with an internal HVAC unit and aged water for humidification. With the rebuilt (original) radon mitigation system, the new low-radon cleanroom has already achieved a $>$$\,$300$\times$ reduction from an input activity of $58.6\pm0.7$$\,$Bq$\,$m$^{-3}$ to a cleanroom activity of $0.13\pm0.06$$\,$Bq$\,$m$^{-3}$.Comment: 5 pages, 4 figures, Proceedings of Low Radioactivity Techniques (LRT) 2015, Seattle, WA, March 18-20, 201

Unintended and accidental medical radiation exposures in radiology: guidelines on investigation and prevention

This paper sets out guidelines for managing radiation exposure incidents involving patients in diagnostic and interventional radiology. The work is based on collation of experiences from representatives of international and national organizations for radiologists, medical physicists, radiographers, regulators, and equipment manufacturers, derived from an International Atomic Energy Agency Technical Meeting. More serious overexposures can result in skin doses high enough to produce tissue reactions, in interventional procedures and computed tomography, most notably from perfusion studies. A major factor involved has been deficiencies in training of staff in operation of equipment and optimization techniques. The use of checklists and time outs before procedures commence, and dose alerts when critical levels are reached during procedures can provide safeguards to reduce risks of these effects occurring. However, unintended and accidental overexposures resulting in relatively small additional doses can take place in any diagnostic or interventional X-ray procedure and it is important to learn from errors that occur, as these may lead to increased risks of stochastic effects. Such events may involve the wrong examinations, procedural errors, or equipment faults. Guidance is given on prevention, investigation and dose calculation for radiology exposure incidents within healthcare facilities. Responsibilities should be clearly set out in formal policies, and procedures should be in place to ensure that root causes are identified and deficiencies addressed. When an overexposure of a patient or an unintended exposure of a foetus occurs, the foetal, organ, skin and/or effective dose may be estimated from exposure data. When doses are very low, generic values for the examination may be sufficient, but a full assessment of doses to all exposed organs and tissues may sometimes be required. The use of general terminology to describe risks from stochastic effects is recommended rather than calculation of numerical values, as these are misleading when applied to individuals

Serum bactericidal activity of colistin and azidothymidine combinations against mcr-1 positive colistin-resistant Escherichia coli.

To examine the serum bactericidal activity of colistin-sulphate (CS) and azidothymidine (AZT) combinations, time-kill curves were performed in native and heat-inactivated human serum with five colistin-resistant and four colistin-susceptible Gram-negative strains. The serum samples were spiked according to the median and minimum plasma peak concentrations measured in a phase 1 clinical study, in which seven healthy subjects received 3-times (q12) 1h-IV-infusions of 4, 2 and 2 million international units (MIU) colistin-methanesulfonate (CMS) co-administered with 200, 100 and 100 mg AZT, respectively. This trial was performed to assess the pharmacokinetics and safety of CMS/AZT-combination therapy. Minimal bactericidal concentrations of CS in native, but not heat-inactivated serum, were strongly reduced compared to Mueller-Hinton-Broth for all tested Enterobacteriaceae, except one colistin-resistant (serum-resistant) strain. For colistin-susceptible strains, the minimum CS concentration after 2 MIU CMS dosage was already bactericidal in native and heat-inactivated serum. Median, but not minimum, CS concentrations after 2 MIU CMS dosage were sufficient to kill the serum-resistant, colistin-resistant E.coli strain in native serum. In heat-inactivated serum, even the median CS concentration after 2 MIU CMS dosage was not bactericidal for all colistin-resistant strains. In general, combinations with AZT accelerated killing of colistin-resistant E.coli or showed bactericidal activity even if the substances alone were not bactericidal. Thus, the combination with AZT potentiates the bactericidal effect of colistin against colistin-resistant E.coli strains. Although the dosage of 2 MIU CMS plus AZT may be sufficient to treat infections with colistin-susceptible strains, for infections caused by colistin-resistant E.coli the dosing should be further optimized

Selectivity of hydrogen chemisorption on clean and lead modified palladium particles; a TPD and photoemission study

This work describes hydrogen chemisorption on clean and lead modified palladium particles obtained from decomposition of PdO. TPD is used as a chemical probe to test the surface properties of several states of metallic palladium relevant in practical selective hydrogenation catalysts. These states differ in oxygen content and the presence of a lead modifier. XPS and UPS data serve as a basis for identifying the surface properties. TPD spectra show a very broad low temperature peak-likely bulk hydride decomposition-and a sharp TPD peak between 330 and 380 K. This latter can be devided into three rather poorly separated subpeaks; addition of Pb does not shift peak maxima but decreases the central subpeak and eliminates the high temperature peak completely. This points to the interaction of Pb with specific surface sites rather than to bulk alloy formation. The enhancement of selectivity in hydrogenation obtained from lead modification is considered as a geometric site blocking effect rather than to arise from a bulk modification of the valence electronic structure of palladium metal