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Sample records for 4th generation fluoroquinolones

  1. 4th Generation ECR Ion Sources

    SciTech Connect

    Lyneis, Claude M.; Leitner, D.; Todd, D.S.; Sabbi, G.; Prestemon, S.; Caspi, S.; Ferracin, P.

    2008-12-01

    The concepts and technical challenges related to developing a 4th generation ECR ion source with an RF frequency greater than 40 GHz and magnetic confinement fields greater than twice Becr will be explored in this paper. Based on the semi-empirical frequency scaling of ECR plasma density with the square of operating frequency, there should be significant gains in performance over current 3rd generation ECR ion sources, which operate at RF frequencies between 20 and 30 GHz. While the 3rd generation ECR ion sources use NbTi superconducting solenoid and sextupole coils, the new sources will need to use different superconducting materials such as Nb3Sn to reach the required magnetic confinement, which scales linearly with RF frequency. Additional technical challenges include increased bremsstrahlung production, which may increase faster than the plasma density, bremsstrahlung heating of the cold mass and the availability of high power continuous wave microwave sources at these frequencies. With each generation of ECR ion sources, there are new challenges to be mastered, but the potential for higher performance and reduced cost of the associated accelerator continue to make this a promising avenue for development.

  2. JLab CW Cryomodules for 4th Generation Light Sources

    SciTech Connect

    Rimmer, Robert; Bundy, Richard; Cheng, Guangfeng; Ciovati, Gianluigi; Clemens, William; Daly, Edward; Henry, James; Hicks, William; Kneisel, Peter; Manning, Stephen; Manus, Robert; Marhauser, Frank; Preble, Joseph; Reece, Charles; Smith, Karl; Stirbet, Mircea; Turlington, Larry; Wang, Haipeng; Wilson, Katherine

    2008-01-23

    Fourth generation light sources hold the prospect of unprecedented brightness and optical beam quality for a wide range of scientific applications. Many of the proposed new facilities will rely on large superconducting radio frequency (SRF) based linacs to provide high energy, low emittance CW electron beams. For high average power applications there is a growing acceptance of energy recovery linac (ERL) technology as the way to support large recirculating currents with modest RF power requirements. CW SRF and high current ERLs are two core competencies at Jefferson Lab. JLab has designed and built a number of CW cryomodules of several different types starting with the original CEBAF design, with variations for higher current in the two generations of JLab’s free-electron laser (FEL), through two intermediate prototypes to the final high-performance module for the 12 GeV upgrade. Each of these represent fully engineered and tested configurations with a variety of specifications that could be considered for possible use in fourth generation light sources. Furthermore JLab has been actively pursuing advanced concepts for highcurrent high-efficiency cryomodules for next generation ERL based FEL’s. These existing and proposed designs span the range from about 1mA single-pass to over 100 mA energy recovered current capability. Specialized configurations also exist for high-current non-energy recovered sections such as the injector region where very high RF power is required. We discuss the performance parameters of these existing and proposed designs and their suitability to different classes of fourth generation light sources.

  3. TID Test Results for 4th Generation iPad(TradeMark)

    NASA Technical Reports Server (NTRS)

    Guertin, S. M.; Allen, G. R.; McClure, S. S.; LaBel, K. A.

    2013-01-01

    TID testing of 4th generation iPads is reported. Of iPad subsystems, results indicate that the charging circuitry and display drivers fail at lowest TID levels. Details of construction are investigated for additional testing of components.

  4. The 4th Generation Light Source at Jefferson Lab

    SciTech Connect

    Stephen Benson; George Biallas; James Boyce; Donald Bullard; James Coleman; David Douglas; H. Dylla; Richard Evans; Pavel Evtushenko; Albert Grippo; Christopher Gould; Joseph Gubeli; David Hardy; Carlos Hernandez-Garcia; Kevin Jordan; John Klopf; Steven Moore; George Neil; Thomas Powers; Joseph Preble; Daniel Sexton; Michelle D. Shinn; Christopher Tennant; Richard Walker; Shukui Zhang; Gwyn Williams

    2007-04-25

    A number of "Grand Challenges" in Science have recently been identified in reports from The National Academy of Sciences, and the U.S. Dept. of Energy, Basic Energy Sciences. Many of these require a new generation of linac-based light source to study dynamical and non-linear phenomena in nanoscale samples. In this paper we present a summary of the properties of such light sources, comparing them with existing sources, and then describing in more detail a specific source at Jefferson Lab. Importantly, the JLab light source has developed some novel technology which is a critical enabler for other new light sources.

  5. Design of a Nb3Sn Magnet for a 4th Generation ECR Ion Source

    SciTech Connect

    Prestemon, S,; Trillaud, F.; Caspi, S.; Ferracin, P.; Sabbi, G. L.; Lyneis, C. M.; Leitner, D.; Todd, D. S.; Hafalia, R.

    2008-08-17

    The next generation of Electron Cyclotron Resonant (ECR) ion sources are expected to operate at a heating radio frequency greater than 40 GHz. The existing 3rd generation systems, exemplified by the state of the art system VENUS, operate in the 10-28 GHz range, and use NbTi superconductors for the confinement coils. The magnetic field needed to confine the plasma scales with the rf frequency, resulting in peak fields on the magnets of the 4th generation system in excess of 10 T. High field superconductors such as Nb{sub 3}Sn must therefore be considered. The magnetic design of a 4th. generation ECR ion source operating at an rf frequency of 56 GHz is considered. The analysis considers both internal and external sextupole configurations, assuming commercially available Nb{sub 3}Sn material properties. Preliminary structural design issues are discussed based on the forces and margins associated with the coils in the different configurations, leading to quantitative data for the determination of a final magnet design.

  6. 4th generation of the 1st level surface detector trigger in the Pierre Auger Observator

    NASA Astrophysics Data System (ADS)

    Szadkowski, Z.

    The proposal of a new 4th generation of the Front-End with the advanced 1st level triggers for the Infill Array of the Pierre Auger Observatory and for the Auger North is described. Newest FPGA chips offer much higher capacity of logic registers and memories, as well as DSP blocks. The calibration channel, previously supported by an external dual-port RAM, has been fully implemented into FPGA chip, through a large internal memory. In turn DSP blocks allowed on implementation of much more sophisticated spectral trigger algorithms. A single chip simplified board design, newer architecture of FPGA reduced resouces utilization and power consumption. Higher sampling in the new Front- End in comparison with previous 40 MHz designs as well as free resources for new detection algotithms can be a good platform for CR radio detection technique at Auger enhancing a duty cycle for the detection of UHECR’s.

  7. [Analysis of the 4th generation outer space bred Angelica dahurica by FTIR spectroscopy].

    PubMed

    Zhu, Yan-ying; Wu, Peng-le; Liu, Mei-yi; Wang, Zhi-zhou; Guo, Xi-hua; Guan, Ying

    2012-03-01

    The major components of the 4th generation outer space bred angelica and the ground group were determined and analyzed by Fourier transform infrared spectroscopy (FTIR) and second derivative spectrum, considering the large mutation of the plants with space mutagenesis. The results show that the content of the coumarin (1741 cm(-1)), which is the main active components of the space angelica dahurica increased, and the content of the protein (1 459, 1 419 cm(-1)) and the fat (930 cm(-1)) increased slightly, whereas the content of the starch and the dietary fiber reduced drastically. There are obvious differences between the peak values of the second derivative spectra of the plants, revealing that the outer space angelica dahurica contained amine component at 1 279 cm(-1). Space mutation breeding is favor of breeding angelica with better idiosyncrasy.

  8. Conditions for the generation of cytotoxic CD4+ Th cells that enhance CD8+ CTL-mediated tumor regression

    PubMed Central

    Li, Kunyu; Baird, Margaret; Yang, Jianping; Jackson, Chris; Ronchese, Franca; Young, Sarah

    2016-01-01

    Adoptive cell therapies (ACTs) using tumor-reactive T cells have shown clinical benefit and potential for cancer treatment. While the majority of the current ACT are focused on using CD8+ cytotoxic T lymphocytes (CTL), others have shown that the presence of tumor-reactive CD4+ T helper (Th) cells can greatly enhance the anti-tumor activity of CD8+ CTL. However, difficulties in obtaining adequate numbers of CD4+ Th cells through in vitro expansion can limit the application of CD4 Th cells in ACT. This study aims to optimize the culture conditions for mouse CD4 T cells to provide basic information for animal studies of ACT using CD4 T cells. Taking advantage of the antigen-specificity of CD4+ Th cells from OT-II transgenic mice, we examined different methodologies for generating antigen-specific CD4+ Th1 cells in vitro. We found that cells grown in complete advanced-DMEM/F12 medium supplemented with low-dose IL-2 and IL-7 induced substantial cell expansion. These Th cells were Th1-like, as they expressed multiple Th1-cytokines and exhibited antigen-specific cytotoxicity. In addition co-transfer of these CD4+ Th1-like cells with CD8+ CTL significantly enhanced tumor regression, leading to complete cure in 80% of mice bearing established B16-OVA. These observations indicate that the CD4+ Th1-like cells generated using the method we optimized are functionally active to eliminate their target cells, and can also assist CD8+ CTL to enhance tumor regression. The findings of this study provide valuable data for further research into in vitro expansion of CD4+ Th1-like cells, with potential applications to cancer treatment involving ACT. PMID:27588200

  9. Conditions for the generation of cytotoxic CD4(+) Th cells that enhance CD8(+) CTL-mediated tumor regression.

    PubMed

    Li, Kunyu; Baird, Margaret; Yang, Jianping; Jackson, Chris; Ronchese, Franca; Young, Sarah

    2016-08-01

    Adoptive cell therapies (ACTs) using tumor-reactive T cells have shown clinical benefit and potential for cancer treatment. While the majority of the current ACT are focused on using CD8(+) cytotoxic T lymphocytes (CTL), others have shown that the presence of tumor-reactive CD4(+) T helper (Th) cells can greatly enhance the anti-tumor activity of CD8(+) CTL. However, difficulties in obtaining adequate numbers of CD4(+) Th cells through in vitro expansion can limit the application of CD4 Th cells in ACT. This study aims to optimize the culture conditions for mouse CD4 T cells to provide basic information for animal studies of ACT using CD4 T cells. Taking advantage of the antigen-specificity of CD4(+) Th cells from OT-II transgenic mice, we examined different methodologies for generating antigen-specific CD4(+) Th1 cells in vitro. We found that cells grown in complete advanced-DMEM/F12 medium supplemented with low-dose IL-2 and IL-7 induced substantial cell expansion. These Th cells were Th1-like, as they expressed multiple Th1-cytokines and exhibited antigen-specific cytotoxicity. In addition co-transfer of these CD4(+) Th1-like cells with CD8(+) CTL significantly enhanced tumor regression, leading to complete cure in 80% of mice bearing established B16-OVA. These observations indicate that the CD4(+) Th1-like cells generated using the method we optimized are functionally active to eliminate their target cells, and can also assist CD8(+) CTL to enhance tumor regression. The findings of this study provide valuable data for further research into in vitro expansion of CD4(+) Th1-like cells, with potential applications to cancer treatment involving ACT. PMID:27588200

  10. Reliability of a new 4th generation FloTrac algorithm to track cardiac output changes in patients receiving phenylephrine.

    PubMed

    Ji, Fuhai; Li, Jian; Fleming, Neal; Rose, David; Liu, Hong

    2015-08-01

    Phenylephrine is often used to treat intra-operative hypotension. Previous studies have shown that the FloTrac cardiac monitor may overestimate cardiac output (CO) changes following phenylephrine administration. A new algorithm (4th generation) has been developed to improve performance in this setting. We performed a prospective observational study to assess the effects of phenylephrine administration on CO values measured by the 3rd and 4th generation FloTrac algorithms. 54 patients were enrolled in this study. We used the Nexfin, a pulse contour method shown to be insensitive to vasopressor administration, as the reference method. Radial arterial pressures were recorded continuously in patients undergoing surgery. Phenylephrine administration times were documented. Arterial pressure recordings were subsequently analyzed offline using three different pulse contour analysis algorithms: FloTrac 3rd generation (G3), FloTrac 4th generation (G4), and Nexfin (nf). One minute of hemodynamic measurements was analyzed immediately before phenylephrine administration and then repeated when the mean arterial pressure peaked. A total of 157 (4.6 ± 3.2 per patient, range 1-15) paired sets of hemodynamic recordings were analyzed. Phenylephrine induced a significant increase in stroke volume (SV) and CO with the FloTrac G3, but not with FloTrac G4 or Nexfin algorithms. Agreement between FloTrac G3 and Nexfin was: 0.23 ± 1.19 l/min and concordance was 51.1%. In contrast, agreement between FloTrac G4 and Nexfin was: 0.19 ± 0.86 l/min and concordance was 87.2%. In conclusion, the pulse contour method of measuring CO, as implemented in FloTrac 4th generation algorithm, has significantly improved its ability to track the changes in CO induced by phenylephrine.

  11. A laboratory model of post-Newtonian gravity with high power lasers and 4th generation light sources

    NASA Astrophysics Data System (ADS)

    Gregori, G.; Levy, M. C.; Wadud, M. A.; Crowley, B. J. B.; Bingham, R.

    2016-04-01

    Using the post-Newtonian formalism of gravity, we attempt to calculate the x-ray Thomson scattering cross section of electrons that are accelerated in the field of a high intensity optical laser. We show that our results are consistent with previous calculations, suggesting that the combination of high power laser and 4th generation light sources may become a powerful platform to test models exploring high order corrections to the Newtonian gravity.

  12. Design of Hanford Site 4th Generation Multi Function Corrosion Monitoring System

    SciTech Connect

    NORMAN, E.C.

    2000-08-30

    This document describes the design of the fourth-generation corrosion monitoring system scheduled to be installed in DST 241-AN-104 early in fiscal year 2001. A fourth-generation multi-function corrosion monitoring system has been designed for installation into a DST in the 241-AN farm at the Hanford Site in FY 2001. Improvements and upgrades from the third-generation system (installed in 241-AN-105) that have been incorporated into the fourth-generation system include: Addition of a built-in water lance to assist installation of probe into tanks with a hard crust layer at the surface of the waste; and Improvement of the electrode mounting apparatus used to attach the corrosion monitoring electrodes to the stainless steel probe body (new design simplifies probe assembly/wiring). These new features improve on the third-generation design and yield a system that is easier to fabricate and install, provides for a better understanding of the relationship between corrosion and other tank operating parameters, and optimizes the use of the riser that houses the probe in the tank.

  13. The ARC-EN-CIEL French 4th Generation Light Source

    NASA Astrophysics Data System (ADS)

    Bruni, C.; Couprie, M. E.; Chubar, O.; Loulergue, A.; Nahon, L.; Carré, B.; Garzella, D.; Labat, M.; Lambert, G.; Monot, P.; Jablonka, M.; Méot, F.; Mosnier, A.; Marquès, J. R.; Ortega, J. M.; Nutarelli, D.

    2007-01-01

    ARC-EN-CIEL (Accelerator-Radiation Complex for Enhanced Coherent Intense Extended Light) proposal is based on a CW 1 GeV superconducting linear accelerator delivering high charge, subpicosecond, low emittance electron bunches with a high repetition rate (1 kHz). The FEL uses High Harmonics Generation in gases in a High Gain Harmonic Generation scheme, leading to a rather compact solution. The radiation extends down to 0.8 nm with the non-linear harmonics and reproduces the good longitudinal and transverse coherence of the harmonics generated in gas. Optional beam loops, foreseen to increase the beam current or the energy, will accommodate infrared CSR source, femtosecond undulator sources in the VUV and X-ray ranges, and a FEL oscillator in the 10 nm range. An important synergy is expected between accelerator and laser communities, in particular for electron plasma acceleration tests.

  14. Rare decays of the Z and the standard model, 4th generation, and beyond

    SciTech Connect

    Weiler, T.J.

    1989-01-01

    Several issues in rare decays of the Z are addressed. The rate for flavor-changing Z decay grows as the fourth power of the fermion masses internal to the quantum loop, and so offers a window to the existence of ultraheavy (m > M{sub W}) fermions. In the standard model, with three generations, BR(Z {yields} bs) < 10{sup -7} and BR(Z{yields}tc)<10{sup -13}. With four generations, BR(Z {yields} bb{sub 4}) may be as large as 10{sup -5} if m{sub b4} < M{sub Z}; and similarly for BR(Z {yields} N{sub 4}v), where N{sub 4} is the possibly heavy fourth generation neutrino. In supersymmetric and other two Higgs doublet models, BR(Z {yields} tc) may be as large as 5 {times} 10{sup -6} in the three generation scheme. With minimal supersymmetry, the reaction Z {yields} H{gamma} is guaranteed to go, with a parameter-dependent branching ratio of 10{sup -6 {plus minus} 3}. With mirror fermions or exotic E{sub 6} fermions, the branching ratios for Z {yields} ct (70 GeV), Z {yields} {mu}{tau}, and Z {yields} bb{sub 4} (70 GeV) are typically 10{sup -4}, 10{sup -4}, and 10{sup -3} respectively, clearly measurable at LEP. Depending on unknown quark masses, the Z may mix with vector (b{sub 4}{bar b}{sub 4}) and the W may mix with vector (t{bar b}) or (t{bar s}). CP violating asymmetries in flavor-changing Z decay are immeasurably small in the standard model, but may be large in supersymmetric and other nonstandard models. 28 refs.

  15. Laboratory Astrophysics with High Power Lasers and 4th Generation Light Sources

    NASA Astrophysics Data System (ADS)

    Gregori, Gianluca

    2013-10-01

    The combination of high power optical lasers and free electron lasers operating at short wavelength (in the x-ray regime) has opened new avenues for laboratory astrophysics, where exotic states of matter can now be generated and probed with high accuracy. We will review a few examples of recent experiments performed at the Linac Coherent Light Source (LCLS) free electron laser operating in Stanford (CA), but also discuss future applications. We will focus our discussion on the following three examples: 1) Laboratory analogues of white dwarf envelopes and the physics of strongly coupled plasmas near crystallization; 2) scaled laboratory experiments to investigate magnetized and radiative shocks; and 3) possible proposals for testing strong gravity analogues using x-ray Thomson scattering. This work was partially the European Research Council under the European Community's Seventh Framework Programme.

  16. Development of Partially-Coherent Wavefront Propagation Simulation Methods for 3rd and 4th Generation Synchrotron Radiation Sources.

    SciTech Connect

    Chubar O.; Berman, L; Chu, Y.S.; Fluerasu, A.; Hulbert, S.; Idir, M.; Kaznatcheev, K.; Shapiro, D.; Baltser, J.

    2012-04-04

    Partially-coherent wavefront propagation calculations have proven to be feasible and very beneficial in the design of beamlines for 3rd and 4th generation Synchrotron Radiation (SR) sources. These types of calculations use the framework of classical electrodynamics for the description, on the same accuracy level, of the emission by relativistic electrons moving in magnetic fields of accelerators, and the propagation of the emitted radiation wavefronts through beamline optical elements. This enables accurate prediction of performance characteristics for beamlines exploiting high SR brightness and/or high spectral flux. Detailed analysis of radiation degree of coherence, offered by the partially-coherent wavefront propagation method, is of paramount importance for modern storage-ring based SR sources, which, thanks to extremely small sub-nanometer-level electron beam emittances, produce substantial portions of coherent flux in X-ray spectral range. We describe the general approach to partially-coherent SR wavefront propagation simulations and present examples of such simulations performed using 'Synchrotron Radiation Workshop' (SRW) code for the parameters of hard X-ray undulator based beamlines at the National Synchrotron Light Source II (NSLS-II), Brookhaven National Laboratory. These examples illustrate general characteristics of partially-coherent undulator radiation beams in low-emittance SR sources, and demonstrate advantages of applying high-accuracy physical-optics simulations to the optimization and performance prediction of X-ray optical beamlines in these new sources.

  17. 4th Annual SATN Conference 2011: Curriculum Transformation at Universities of Technology: Towards Development of New Generation Universities

    ERIC Educational Resources Information Center

    Mthembu, T.

    2012-01-01

    The South African Technology Network (SATN) would like to thank the Editor of the "South African Journal of Higher Education" (SAJHE) for the opportunity to publish papers read at the 4th Annual SATN Conference that was hosted by Central University of Technology and held in Bloemfontein in November 2011. The journal makes it possible for…

  18. Comparative clinical study of conjunctival toxicities of newer generation fluoroquinolones without the influence of preservatives

    PubMed Central

    Park, Han Sang; Lee, Jun Hun; Kim, Hong Kyun

    2015-01-01

    AIM To compare the conjunctival epithelial toxicities of three newer-generation fluoroquinolones without preservatives. METHODS In a prospective, randomized, double blind comparative study, 47 eyes of 47 patients with a primary pterygium were enrolled, and divided randomly into three groups (levofloxacin 0.5%, gatifloxacin 0.3%, and moxifloxacin 0.5%). After pterygium surgery with the same conjunctival autograft technique, each patient maintained a regimen with a randomly assigned fluoroquinolone eye drop. Patients were examined every other day after surgery until the epithelium had completely healed. Photos were taken and used to measure the area of residual epithelial defects. Conjunctival healing time and speed (initial defect area/healing time (mm2/d) compared in each group using Kruskal-Wallis tests. RESULTS There were no significant differences in mean age, gender, and conjunctival defect size of the donor site between these groups. However, the mean of conjunctival healing time and speed were statistically different in each group. The mean of conjunctival epithelial healing time was 8.93±2.69d (levofloxacin group), 10.31±2.96d (gatifloxacin group), and 13.50±4.10d (moxifloxacin group), P=0.006. The mean conjuctival epithelial healing speed was 6.18±1.39 mm2/d (levofloxacin group), 5.52±1.68 mm2/d (gatifloxacin group), and 4.40±1.30 mm2/d (moxifloxacin group), P=0. 003. CONCLUSION Without the influence of preservatives, levofloxacin and gatifloxacin might be less toxic to the regeneration of conjunctival epithelial cells and cause a faster conjunctival wound healing relative to moxifloxacin. PMID:26682177

  19. Nonlinearly generated harmonic signals in ultra-small waveguides with magnetic films: Tunable enhancements of 2nd and 4th harmonics

    NASA Astrophysics Data System (ADS)

    Marsh, J.; Zagorodnii, V.; Celinski, Z.; Camley, R. E.

    2012-03-01

    The nonlinear generation of high harmonic signals (up to 5th harmonic) is explored in an ultra-small waveguide which contains a thin ferromagnetic film. The strength of the different harmonics is highly tunable. In particular, the power in the 2nd and 4th harmonic signals may be enhanced by over two orders of magnitude by varying the direction of a static magnetic field with respect to the long axis of the waveguide. In contrast, the 3rd and 5th harmonics are relatively insensitive to the direction of the magnetic field. The experimental results are explained by analytical and numerical calculations.

  20. Third and fourth generation fluoroquinolone antibacterials: a systematic review of safety and toxicity profiles.

    PubMed

    Sousa, Joana; Alves, Gilberto; Fortuna, Ana; Falcão, Amilcar

    2014-01-01

    In the last decade, several third and fourth generation fluoroquinolones (FQs) have been approved for clinical use. These new agents exhibit a more potent and broader-spectrum antibacterial activity and improved pharmacokinetic properties in comparison to the earlier FQs. Although new FQs are generally safe and well tolerated, moderate-to-severe toxicity events have been reported for some of them, leading to their restriction, suspension or even withdrawal from the market. The most common FQ-related adverse effects (AEs) are usually mild and involve the gastrointestinal tract (e.g. nausea and diarrhea) and the central nervous system (e.g. headache and dizziness). Uncommon, but severe AEs (e.g. arthropathy, QTc interval prolongation, dysglycaemia and phototoxicity) and idiosyncratic reactions (e.g. hepatitis and hemolytic anemia) have also been reported and will be discussed throughout this paper. The evidence currently available suggests that AEs can be inherent to the FQ class or can be associated with a particular chemical moiety of the molecular structure of each FQ, thus varying in frequency, severity and nature. The main goal of this review is to provide a systematic evaluation of safety and tolerability data of the newer FQs with emphasis on those currently marketed.

  1. Efficient 2(nd) and 4(th) harmonic generation of a single-frequency, continuous-wave fiber amplifier.

    PubMed

    Sudmeyer, Thomas; Imai, Yutaka; Masuda, Hisashi; Eguchi, Naoya; Saito, Masaki; Kubota, Shigeo

    2008-02-01

    We demonstrate efficient cavity-enhanced second and fourth harmonic generation of an air-cooled, continuous-wave (cw), single-frequency 1064 nm fiber-amplifier system. The second harmonic generator achieves up to 88% total external conversion efficiency, generating more than 20-W power at 532 nm wavelength in a diffraction-limited beam (M(2) < 1.05). The nonlinear medium is a critically phase-matched, 20-mm long, anti-reflection (AR) coated LBO crystal operated at 25 degrees C. The fourth harmonic generator is based on an AR-coated, Czochralski-grown beta-BaB(2)O(4) (BBO) crystal optimized for low loss and high damage threshold. Up to 12.2 W of 266-nm deep-UV (DUV) output is obtained using a 6-mm long critically phase-matched BBO operated at 40 degrees C. This power level is more than two times higher than previously reported for cw 266-nm generation. The total external conversion efficiency from the fundamental at 1064 nm to the fourth harmonic at 266 nm is >50%.

  2. BEAM DYNAMICS STUDIES OF A HIGH-REPETITION RATE LINAC-DRIVER FOR A 4TH GENERATION LIGHT SOURCE

    SciTech Connect

    Ventturini, M.; Corlett, J.; Emma, P.; Papadopoulos, C.; Penn, G.; Placidi, M.; Qiang, J.; Reinsch, M.; Sannibale, F.; Steier, C.; Sun, C.; Wells, R.

    2012-05-18

    We present recent progress toward the design of a super-conducting linac driver for a high-repetition rate FEL-based soft x-ray light source. The machine is designed to accept beams generated by the APEX photo-cathode gun operating with MHz-range repetition rate and deliver them to an array of SASE and seeded FEL beamlines. We review the current baseline design and report results of beam dynamics studies.

  3. Testing quantum mechanics in non-Minkowski space-time with high power lasers and 4(th) generation light sources.

    PubMed

    Crowley, B J B; Bingham, R; Evans, R G; Gericke, D O; Landen, O L; Murphy, C D; Norreys, P A; Rose, S J; Tschentscher, Th; Wang, C H-T; Wark, J S; Gregori, G

    2012-01-01

    A common misperception of quantum gravity is that it requires accessing energies up to the Planck scale of 10¹⁹ GeV, which is unattainable from any conceivable particle collider. Thanks to the development of ultra-high intensity optical lasers, very large accelerations can be now the reached at their focal spot, thus mimicking, by virtue of the equivalence principle, a non Minkowski space-time. Here we derive a semiclassical extension of quantum mechanics that applies to different metrics, but under the assumption of weak gravity. We use our results to show that Thomson scattering of photons by uniformly accelerated electrons predicts an observable effect depending upon acceleration and local metric. In the laboratory frame, a broadening of the Thomson scattered x ray light from a fourth generation light source can be used to detect the modification of the metric associated to electrons accelerated in the field of a high power optical laser.

  4. Testing quantum mechanics in non-Minkowski space-time with high power lasers and 4th generation light sources

    PubMed Central

    Crowley, B. J. B.; Bingham, R.; Evans, R. G.; Gericke, D. O.; Landen, O. L.; Murphy, C. D.; Norreys, P. A.; Rose, S. J.; Tschentscher, Th; Wang, C. H.-T; Wark, J. S.; Gregori, G.

    2012-01-01

    A common misperception of quantum gravity is that it requires accessing energies up to the Planck scale of 1019 GeV, which is unattainable from any conceivable particle collider. Thanks to the development of ultra-high intensity optical lasers, very large accelerations can be now the reached at their focal spot, thus mimicking, by virtue of the equivalence principle, a non Minkowski space-time. Here we derive a semiclassical extension of quantum mechanics that applies to different metrics, but under the assumption of weak gravity. We use our results to show that Thomson scattering of photons by uniformly accelerated electrons predicts an observable effect depending upon acceleration and local metric. In the laboratory frame, a broadening of the Thomson scattered x ray light from a fourth generation light source can be used to detect the modification of the metric associated to electrons accelerated in the field of a high power optical laser. PMID:22768381

  5. Gas dynamics and heat transfer in a packed pebble-bed reactor for the 4th generation nuclear energy

    NASA Astrophysics Data System (ADS)

    Abdulmohsin, Rahman

    -AlOx-Al junctions, we show that, despite excellent temperature stability, temperature fluctuations induce observable critical current fluctuations. Particularly, becuase 1/ f critical current noise has decreased with improved fabrication techniques in recent years, it is important to understand and eliminate this additional noise source. Next, we introduce a numerical method of calculating the mean square flux noise F2 from independently fluctuating spins on the surface of thin-film loops of arbitrary geometry. By reciprocity, F2 is proportional to Br2 , where B(r) is the magnetic field generated by a circulating current around the loop and r varies over the loop surface. By discretizing the loop nonuniformly, we efficiently and accurately compute the current distribution and resulting magnetic field, which may vary rapidly across the loop. We use this method to compute F2 in a number of scenarios in which we systematically vary physical parameters of the loop. We compare our simulations to an earlier analytic result predicting that F2 ∝ R/W in the limit where the loop radius R is much greater than the linewidth W. We further show that the previously neglected contribution of edge spins to F2 is significant---even dominant---in narrow-linewidth loops. To calculate theoretical dephasing rates in qubits, we consider flux noise with a spectral density Sphi( f) = A2/ (f/1 Hz) alpha, where A is of the order of 1 muphi 0 Hz--1/2 and 0.6 ≤ alpha ≤ 1.2; applied flux, our calculations of the dependence of the pure dephasing time tau φ Ramsey and echo pulse sequences on alpha for fixed A show that tauφ decreases rapidly as alpha is reduced. We find that tauφ is relatively insensitive to the noise bandwidth, f1 ≤ f ≤ f2 for all alpha provided the ultraviolet cutoff frequency f2 > 1/tauφ. We calculate the ratio tauφ,E/tau φ, R of the echo (E) and Ramsey (R) sequences, and the dependence of the decay function on alpha and f2. We investigate the case in which S phi(f0) is fixed

  6. The 4th Thermodynamic Principle?

    SciTech Connect

    Montero Garcia, Jose de la Luz; Novoa Blanco, Jesus Francisco

    2007-04-28

    It should be emphasized that the 4th Principle above formulated is a thermodynamic principle and, at the same time, is mechanical-quantum and relativist, as it should inevitably be and its absence has been one of main the theoretical limitations of the physical theory until today.We show that the theoretical discovery of Dimensional Primitive Octet of Matter, the 4th Thermodynamic Principle, the Quantum Hexet of Matter, the Global Hexagonal Subsystem of Fundamental Constants of Energy and the Measurement or Connected Global Scale or Universal Existential Interval of the Matter is that it is possible to be arrived at a global formulation of the four 'forces' or fundamental interactions of nature. The Einstein's golden dream is possible.

  7. The Leap into 4th Grade

    ERIC Educational Resources Information Center

    Anderson, Mike

    2011-01-01

    Fourth grade is a pivotal year, in which students commonly face increased academic demands. According to Anderson, teachers can help students make a smooth transition to 4th grade by introducing these new challenges in ways that are in line with 4th graders' common developmental characteristics: incredible energy and emotion, industriousness and…

  8. 17. 4th floor roof, view south, 4th and 5th floor ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    17. 4th floor roof, view south, 4th and 5th floor setback to left and atrium structure to right - Sheffield Farms Milk Plant, 1075 Webster Avenue (southwest corner of 166th Street), Bronx, Bronx County, NY

  9. Comparative tolerability of the newer fluoroquinolone antibacterials.

    PubMed

    Ball, P; Mandell, L; Niki, Y; Tillotson, G

    1999-11-01

    The most common adverse effects of the fluoroquinolones involve the gastrointestinal tract, skin and CNS, and are mainly mild and reversible. Of the gastrointestinal events, nausea and vomiting are the most common. Mild hepatic reactions are a class effect, usually presenting as mild transaminase level increases without clinical symptoms. However, postmarketing surveillance has revealed significant hepatotoxicity with trovafloxacin. It is not currently known whether the severe reactions to trovafloxacin are specific to that agent or simply represent an extreme of an emerging class effect. The enormous worldwide usage of, and extensive published adverse effect data on the other fluoroquinolones and naphthyridones suggests the former. In perspective, rare but serious hepatotoxicity has been reported with other fluoroquinolones and the overall incidence of trovafloxacin hepatotoxicity is not dissimilar to that reported with flucloxacillin and amoxicillin-clavulanic acid. CNS reactions vary in severity and include dizziness, convulsions (notably with lomefloxacin) and psychoses. Fluoroquinolones differ in their pro-convulsive activity, relating to their differing potential as gamma-aminobutyric acid antagonists and binding to the N-methyl-D-aspartate receptor. The basis for the increased seizure potential following the coadministration of nonsteroidal anti-inflammatory drugs with certain fluoroquinolones is not fully understood. Fluoroquinolone phototoxicity, caused by the generation of toxic free oxygen species under exposure to UVA radiation, is significantly more common with 8-halogenated compounds. Certain patient groups, e.g. patients with cystic fibrosis, are predisposed to this adverse effect. Murine photocarcinogenicity has been demonstrated with lomefloxacin, but no such effects have been reported in humans. Prolongation of the QTc interval is also a class effect, although cardiac arrhythmias have only been linked with sparfloxacin. Among the newer

  10. 166. GENERAL VIEW DOWN 4TH AVENUE. VIEW NORTHEAST DOWN 4TH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    166. GENERAL VIEW DOWN 4TH AVENUE. VIEW NORTHEAST DOWN 4TH AVE. FROM BUILDING 44 SHOWING, FROM LEFT TO RIGHT, BUILDING 46, 48, 55, AND 50 (PART OF ENLISTED BARRACKS COMPLEX), AND BUILDINGS 17, 16, 484, 483, 374, AND 375 (IN THE WAREHOUSE COMPLEX). - Quonset Point Naval Air Station, Roger Williams Way, North Kingstown, Washington County, RI

  11. Kids & Family Reading Report™. 4th Edition

    ERIC Educational Resources Information Center

    Scholastic Inc., 2013

    2013-01-01

    This report presents the 4th Edition of Scholastic's biannual study of children's and parents' attitudes and behaviors about reading. Much has changed since the first "Kids & Family Reading Report" was issued in 2006, but literacy remains the critical skill needed for school success. Today's children are growing up in a world full of…

  12. Combinatorially-generated library of 6-fluoroquinolone analogs as potential novel antitubercular agents: a chemometric and molecular modeling assessment.

    PubMed

    Minovski, Nikola; Perdih, Andrej; Solmajer, Tom

    2012-05-01

    The virtual combinatorial chemistry approach as a methodology for generating chemical libraries of structurally-similar analogs in a virtual environment was employed for building a general mixed virtual combinatorial library with a total of 53.871 6-FQ structural analogs, introducing the real synthetic pathways of three well known 6-FQ inhibitors. The druggability properties of the generated combinatorial 6-FQs were assessed using an in-house developed drug-likeness filter integrating the Lipinski/Veber rule-sets. The compounds recognized as drug-like were used as an external set for prediction of the biological activity values using a neural-networks (NN) model based on an experimentally-determined set of active 6-FQs. Furthermore, a subset of compounds was extracted from the pool of drug-like 6-FQs, with predicted biological activity, and subsequently used in virtual screening (VS) campaign combining pharmacophore modeling and molecular docking studies. This complex scheme, a powerful combination of chemometric and molecular modeling approaches provided novel QSAR guidelines that could aid in the further lead development of 6-FQs agents.

  13. Fluoroquinolone antimicrobial agents.

    PubMed Central

    Wolfson, J S; Hooper, D C

    1989-01-01

    The fluoroquinolones, a new class of potent orally absorbed antimicrobial agents, are reviewed, considering structure, mechanisms of action and resistance, spectrum, variables affecting activity in vitro, pharmacokinetic properties, clinical efficacy, emergence of resistance, and tolerability. The primary bacterial target is the enzyme deoxyribonucleic acid gyrase. Bacterial resistance occurs by chromosomal mutations altering deoxyribonucleic acid gyrase and decreasing drug permeation. The drugs are bactericidal and potent in vitro against members of the family Enterobacteriaceae, Haemophilus spp., and Neisseria spp., have good activity against Pseudomonas aeruginosa and staphylococci, and (with several exceptions) are less potent against streptococci and have fair to poor activity against anaerobic species. Potency in vitro decreases in the presence of low pH, magnesium ions, or urine but is little affected by different media, increased inoculum, or serum. The effects of the drugs in combination with a beta-lactam or aminoglycoside are often additive, occasionally synergistic, and rarely antagonistic. The agents are orally absorbed, require at most twice-daily dosing, and achieve high concentrations in urine, feces, and kidney and good concentrations in lung, bone, prostate, and other tissues. The drugs are efficacious in treatment of a variety of bacterial infections, including uncomplicated and complicated urinary tract infections, bacterial gastroenteritis, and gonorrhea, and show promise for therapy of prostatitis, respiratory tract infections, osteomyelitis, and cutaneous infections, particularly when caused by aerobic gram-negative bacilli. Fluoroquinolones have also proved to be efficacious for prophylaxis against travelers' diarrhea and infection with gram-negative bacilli in neutropenic patients. The drugs are effective in eliminating carriage of Neisseria meningitidis. Patient tolerability appears acceptable, with gastrointestinal or central nervous

  14. Hypersensitivity to fluoroquinolones

    PubMed Central

    Fernández, Tahia D.; Ariza, Adriana; Palomares, Francisca; Montañez, María I.; Salas, María; Martín-Serrano, Angela; Fernández, Rubén; Ruiz, Arturo; Blanca, Miguel; Mayorga, Cristobalina; Torres, María J.

    2016-01-01

    Abstract Although fluoroquinolones (FQs) are generally well-tolerated antibiotics, increasing numbers of hypersensitivity reactions have been reported. These can be evaluated in vitro by basophil activation tests (BATs); however, sensitivity is not optimal. Many factors could influence sensitivity such as basophil activation markers. The objective of this study was to evaluate the influence of 2 different activations markers, CD63 and CD203c, on the sensitivity of BAT to FQ. We studied 17 patients with immediate allergic reactions to FQ. BAT was performed with moxifloxacin and ciprofloxacin using CD193 (CCR3) for basophil selection and CD203c or CD63 as activation markers. Stimulation with ciprofloxacin induced a significantly higher expression of CD63 in ciprofloxacin-allergic patients compared to moxifloxacin-allergic patients (P = 0.002). In patients allergic to moxifloxacin with anaphylactic shock, we have observed an increase in the percentage of cells that upregulate CD203c, whereas patients with anaphylaxis preferentially upregulate CD63. The best sensitivity–specificity was obtained using a cutoff of 3 and the culprit FQ, using CD203c for moxifloxacin-allergic patients (sensitivity = 36.4%; specificity = 94.4%), and CD63 for ciprofloxacin-allergic patients (sensitivity = 83.3%; specificity = 88.9%). A negative correlation was found between the upregulation of CD63 and CD203c and the time interval between the reaction occurrence and the performance of the test (Spearman r = −0.446; P < 0.001 for CD63 and Spearman r = −0.386; P < 0.001 for CD203c). The performance of BAT for FQ allergy must be optimized for each drug, taking into account possible differences in the stimulation mechanism that leads to the upregulation of different activation markers. PMID:27281069

  15. Large-format, high-speed, X-ray pnCCDs combined with electron and ion imaging spectrometers in a multipurpose chamber for experiments at 4th generation light sources

    NASA Astrophysics Data System (ADS)

    Strüder, Lothar; Epp, Sascha; Rolles, Daniel; Hartmann, Robert; Holl, Peter; Lutz, Gerhard; Soltau, Heike; Eckart, Rouven; Reich, Christian; Heinzinger, Klaus; Thamm, Christian; Rudenko, Artem; Krasniqi, Faton; Kühnel, Kai-Uwe; Bauer, Christian; Schröter, Claus-Dieter; Moshammer, Robert; Techert, Simone; Miessner, Danilo; Porro, Matteo; Hälker, Olaf; Meidinger, Norbert; Kimmel, Nils; Andritschke, Robert; Schopper, Florian; Weidenspointner, Georg; Ziegler, Alexander; Pietschner, Daniel; Herrmann, Sven; Pietsch, Ullrich; Walenta, Albert; Leitenberger, Wolfram; Bostedt, Christoph; Möller, Thomas; Rupp, Daniela; Adolph, Marcus; Graafsma, Heinz; Hirsemann, Helmut; Gärtner, Klaus; Richter, Rainer; Foucar, Lutz; Shoeman, Robert L.; Schlichting, Ilme; Ullrich, Joachim

    2010-03-01

    Fourth generation accelerator-based light sources, such as VUV and X-ray Free Electron Lasers (FEL), deliver ultra-brilliant (˜10 12-10 13 photons per bunch) coherent radiation in femtosecond (˜10-100 fs) pulses and, thus, require novel focal plane instrumentation in order to fully exploit their unique capabilities. As an additional challenge for detection devices, existing (FLASH, Hamburg) and future FELs (LCLS, Menlo Park; SCSS, Hyogo and the European XFEL, Hamburg) cover a broad range of photon energies from the EUV to the X-ray regime with significantly different bandwidths and pulse structures reaching up to MHz micro-bunch repetition rates. Moreover, hundreds up to trillions of fragment particles, ions, electrons or scattered photons can emerge when a single light flash impinges on matter with intensities up to 10 22 W/cm 2. In order to meet these challenges, the Max Planck Advanced Study Group (ASG) within the Center for Free Electron Laser Science (CFEL) has designed the CFEL-ASG MultiPurpose (CAMP) chamber. It is equipped with specially developed photon and charged particle detection devices dedicated to cover large solid-angles. A variety of different targets are supported, such as atomic, (aligned) molecular and cluster jets, particle injectors for bio-samples or fixed target arrangements. CAMP houses 4π solid-angle ion and electron momentum imaging spectrometers ("reaction microscope", REMI, or "velocity map imaging", VMI) in a unique combination with novel, large-area, broadband (50 eV-25 keV), high-dynamic-range, single-photon-counting and imaging X-ray detectors based on the pnCCDs. This instrumentation allows a new class of coherent diffraction experiments in which both electron and ion emission from the target may be simultaneously monitored. This permits the investigation of dynamic processes in this new regime of ultra-intense, high-energy radiation—matter interaction. After an introduction into the salient features of the CAMP chamber and

  16. Fluoroquinolones as potential photochemotherapeutic agents: covalent addition to guanosine monophosphate.

    PubMed

    Fasani, Elisa; Manet, Ilse; Capobianco, Massimo L; Monti, Sandra; Pretali, Luca; Albini, Angelo

    2010-08-21

    The triplet aryl cation photochemically generated from fluoroquinolones bearing a fluoro atom at position 8 attacks guanosine monophosphate (k(r) > 10(9) M(-1)s(-1)) and forms covalent adducts. The reaction is a model for the implementation of oxygen-independent photochemotherapy. PMID:20571620

  17. The use of systemic and topical fluoroquinolones.

    PubMed

    Bradley, John S; Jackson, Mary Anne

    2011-10-01

    Appropriate prescribing practices for fluoroquinolones are essential as evolving resistance patterns are considered, additional treatment indications are identified, and the toxicity profile of fluoroquinolones in children becomes better defined. Earlier recommendations for systemic therapy remain; expanded uses of fluoroquinolones for the treatment of certain infections are outlined in this report. Although fluoroquinolones are reasonably safe in children, clinicians should be aware of the specific adverse reactions. Use of fluoroquinolones in children should continue to be limited to treatment of infections for which no safe and effective alternative exists.

  18. In vitro potency and efficacy favor later generation fluoroquinolones for treatment of canine and feline Escherichia coli uropathogens in the United States.

    PubMed

    Liu, Xiaoqiang; Boothe, Dawn M; Jin, Yaping; Thungrat, Kamoltip

    2013-02-01

    Information regarding in vitro activity of newer fluoroquinolones (FQs) is limited despite increasing resistance in canine or feline pathogenic Escherichia coli (E. coli). This study describes in vitro potency and efficacy toward E. coli of seven FQs grouped according to similarities in chemical structure: enrofloxacin, ciprofloxacin, orbifloxacin (first-group), levofloxacin, marbofloxacin (second-group) and pradofloxacin, moxifloxacin (third-group; latest S, S-pyrrolidino-piperidine at C-7). Potency measures included minimum inhibitory concentration (MIC) (geometric mean MIC, MIC(50), MIC(90)); and mutant prevention concentration (MPC) for FQ susceptible isolates only. In vitro efficacy measures included relative susceptibility (MIC(BP-S):MIC) or resistance (MIC:MIC(BP-R)) and mutant selection window (MSW) (MPC:MIC). For enrofloxacin susceptible isolates, mean MIC (μg/ml) was least for each third-group drug and ciprofloxacin and greatest for enrofloxacin and orbifloxacin (P = 0.006). For enrofloxacin susceptible isolates, MPC were below MIC:MIC(BP-R) and least for pradofloxacin (0.29 ± 0.16 μg/ml) and greatest for enrofloxacin (1.55 ± 0.55 μg/ml) (P = 0.006). MSW was least for pradofloxacin (55 ± 30) and greatest for ciprofloxacin (152 ± 76) (P = 0.0024). MIC(BP-S):MIC was greatest (P = 0.025) for pradofloxacin (190.1 ± 0.61) and least for enrofloxacin (23.53 ± 0.83). For FQ susceptible isolates, FQs MIC:MIC(BP-R) may serve as a surrogate for MPC. Because in vitro efficacy was greatest for pradofloxacin; it might be preferred for treatment of urinary tract infections (UTIs) associated with FQ susceptible E. coli uropathogens.

  19. Gyrase Mutations Are Associated with Variable Levels of Fluoroquinolone Resistance in Mycobacterium tuberculosis

    PubMed Central

    Jacobson, Karen R.; Franke, Molly F.; Kaur, Devinder; Sloutsky, Alex; Mitnick, Carole D.; Murray, Megan

    2016-01-01

    Molecular diagnostics that rapidly and accurately predict resistance to fluoroquinolone drugs and especially later-generation agents promise to improve treatment outcomes for patients with multidrug-resistant tuberculosis and prevent the spread of disease. Mutations in the gyr genes are known to confer most fluoroquinolone resistance, but knowledge about the effects of gyr mutations on susceptibility to early- versus later-generation fluoroquinolones and about the role of mutation-mutation interactions is limited. Here, we sequenced the full gyrA and gyrB open reading frames in 240 multidrug-resistant and extensively drug-resistant tuberculosis strains and quantified their ofloxacin and moxifloxacin MIC by testing growth at six concentrations for each drug. We constructed a multivariate regression model to assess both the individual mutation effects and interactions on the drug MICs. We found that gyrB mutations contribute to fluoroquinolone resistance both individually and through interactions with gyrA mutations. These effects were statistically significant. In these clinical isolates, several gyrA and gyrB mutations conferred different levels of resistance to ofloxacin and moxifloxacin. Consideration of gyr mutation combinations during the interpretation of molecular test results may improve the accuracy of predicting the fluoroquinolone resistance phenotype. Further, the differential effects of gyr mutations on the activity of early- and later-generation fluoroquinolones requires further investigation and could inform the selection of a fluoroquinolone for treatment. PMID:26763957

  20. The 4th order GISS model of the global atmosphere

    NASA Technical Reports Server (NTRS)

    Kalnay-Rivas, E.; Bayliss, A.; Storch, J.

    1977-01-01

    The new GISS 4th order model of the global atmosphere is described. It is based on 4th order quadratically conservative differences with the periodic application of a 16th order filter on the sea level pressure and potential temperature equations, a combination which is approximately enstrophy conserving. Several short range forecasts indicate a significant improvement over 2nd order forecasts with the same resolution (approximately 400 km). However the 4th order forecasts are somewhat inferior to 2nd order forecasts with double resolution. This is probably due to the presence of short waves in the range between 1000 km and 2000 km, which are computed more accurately by the 2nd order high resolution model. An operation count of the schemes indicates that with similar code optimization, the 4th order model will require approximately the same amount of computer time as the 2nd order model with the same resolution. It is estimated that the 4th order model with a grid size of 200 km provides enough accuracy to make horizontal truncation errors negligible over a period of a week for all synoptic scales (waves longer than 1000 km).

  1. European Code against Cancer, 4th Edition: Tobacco and cancer.

    PubMed

    Leon, Maria E; Peruga, Armando; McNeill, Ann; Kralikova, Eva; Guha, Neela; Minozzi, Silvia; Espina, Carolina; Schüz, Joachim

    2015-12-01

    Tobacco use, and in particular cigarette smoking, is the single largest preventable cause of cancer in the European Union (EU). All tobacco products contain a wide range of carcinogens. The main cancer-causing agents in tobacco smoke are polycyclic aromatic hydrocarbons, tobacco-specific N-nitrosamines, aromatic amines, aldehydes, and certain volatile organic compounds. Tobacco consumers are also exposed to nicotine, leading to tobacco addiction in many users. Cigarette smoking causes cancer in multiple organs and is the main cause of lung cancer, responsible for approximately 82% of cases. In 2012, about 313,000 new cases of lung cancer and 268,000 lung cancer deaths were reported in the EU; 28% of adults in the EU smoked tobacco, and the overall prevalence of current use of smokeless tobacco products was almost 2%. Smokeless tobacco products, a heterogeneous category, are also carcinogenic but cause a lower burden of cancer deaths than tobacco smoking. One low-nitrosamine product, snus, is associated with much lower cancer risk than other smokeless tobacco products. Smoking generates second-hand smoke (SHS), an established cause of lung cancer, and inhalation of SHS by non-smokers is still common in indoor workplaces as well as indoor public places, and more so in the homes of smokers. Several interventions have proved effective for stopping smoking; the most effective intervention is the use of a combination of pharmacotherapy and behavioural support. Scientific evidence leads to the following two recommendations for individual action on tobacco in the 4th edition of the European Code Against Cancer: (1) "Do not smoke. Do not use any form of tobacco"; (2) "Make your home smoke-free. Support smoke-free policies in your workplace". PMID:26272517

  2. European Code against Cancer, 4th Edition: Tobacco and cancer.

    PubMed

    Leon, Maria E; Peruga, Armando; McNeill, Ann; Kralikova, Eva; Guha, Neela; Minozzi, Silvia; Espina, Carolina; Schüz, Joachim

    2015-12-01

    Tobacco use, and in particular cigarette smoking, is the single largest preventable cause of cancer in the European Union (EU). All tobacco products contain a wide range of carcinogens. The main cancer-causing agents in tobacco smoke are polycyclic aromatic hydrocarbons, tobacco-specific N-nitrosamines, aromatic amines, aldehydes, and certain volatile organic compounds. Tobacco consumers are also exposed to nicotine, leading to tobacco addiction in many users. Cigarette smoking causes cancer in multiple organs and is the main cause of lung cancer, responsible for approximately 82% of cases. In 2012, about 313,000 new cases of lung cancer and 268,000 lung cancer deaths were reported in the EU; 28% of adults in the EU smoked tobacco, and the overall prevalence of current use of smokeless tobacco products was almost 2%. Smokeless tobacco products, a heterogeneous category, are also carcinogenic but cause a lower burden of cancer deaths than tobacco smoking. One low-nitrosamine product, snus, is associated with much lower cancer risk than other smokeless tobacco products. Smoking generates second-hand smoke (SHS), an established cause of lung cancer, and inhalation of SHS by non-smokers is still common in indoor workplaces as well as indoor public places, and more so in the homes of smokers. Several interventions have proved effective for stopping smoking; the most effective intervention is the use of a combination of pharmacotherapy and behavioural support. Scientific evidence leads to the following two recommendations for individual action on tobacco in the 4th edition of the European Code Against Cancer: (1) "Do not smoke. Do not use any form of tobacco"; (2) "Make your home smoke-free. Support smoke-free policies in your workplace".

  3. Fluoroquinolone prophylaxis against febrile neutropenia in areas with high fluoroquinolone resistance--an Asian perspective.

    PubMed

    Ng, Esther Shu-Ting; Liew, Yixin; Koh, Liang Piu; Hsu, Li Yang

    2010-09-01

    Febrile neutropenia remains a major cause of morbidity and mortality in patients receiving chemotherapy. Major prophylactic strategies include granulocyte colony-stimulating factor and antibiotics, the most widely used of which are fluoroquinolones. While fluoroquinolone prophylaxis has been shown to be effective in areas where fluoroquinolone resistance is low, this same efficacy has not been proven in areas where resistance is high, such as in Asia. Given the increase in antimicrobial resistance with the use of prophylaxis, the risks and benefits of this strategy need to be carefully considered. This review presents the evidence for and against fluoroquinolone prophylaxis in areas of high fluoroquinolone resistance.

  4. 4th International Plant Biomechanics Conference Proceedings (Abstracts)

    SciTech Connect

    Frank W. Telewski; Lothar H. Koehler; Frank W. Ewers

    2003-07-20

    The 4th International Plant Biomechanics Conference facilitated an interdisciplinary exchange between scientists, engineers, and educators addressing the major questions encountered in the field of Plant Biomechanics. Subjects covered by the conference include: Evolution; Ecology; Mechanoreception; Cell Walls; Genetic Modification; Applied Biomechanics of Whole Plants, Plant Products, Fibers & Composites; Fluid Dynamics; Wood & Trees; Fracture Mechanics; Xylem Pressure & Water Transport; Modeling; and Introducing Plant Biomechanics in Secondary School Education.

  5. Fluoroquinolone antibiotics in the environment.

    PubMed

    Sukul, Premasis; Spiteller, Michael

    2007-01-01

    Fluoroquinolones (FQs) are used in large amounts for human and animal medical care. They are excreted as parent compound, as conjugates, or as oxidation, hydroxylation, dealkylation, or decarboxylation products of the parent compound. A considerable amount of FQs and their metabolites may reach the soil as constituents of urine, feces, or manure. The residues of FQs in foods of animal origin may pose hazards to consumers through emergence of drug-resistant bacteria. FQs bind strongly to topsoil, reducing the threat of surface water and groundwater contamination. The strong binding of FQs to soil and sediments delays their biodegradation and explains the recalcitrance of FQs. Wastewater treatment is an efficient elimination step (79%-87% removal) for FQs before they enter rivers. FQs are susceptible to photodegradation in aqueous medium, involving oxidation, dealkylation, and cleavage of the piperazine ring.

  6. Birth outcome following maternal use of fluoroquinolones.

    PubMed

    Larsen, H; Nielsen, G L; Schønheyder, H C; Olesen, C; Sørensen, H T

    2001-09-01

    The aim of the study was to examine fetal risk associated with intrauterine exposure to fluoroquinolones. By using on record linkage between a Prescription Database and the Birth Registry in Denmark, the offspring of 57 users of fluoroquinolones and of 17259 patients who had no prescriptive medication during pregnancy, were compared in a cohort study. Among the users, the prevalence rate ratios of congenital abnormalities, preterm birth and low birth weight were 1.30 (95% CI: 0.30-5.30),1.53 (95% CI: 0.62-3.80) and 1.17 (95% CI: 0.15-8.90), respectively. The risk of congenital abnormalities among users of fluoroquinolones during pregnancy was close to unity. Despite these limitations of statistical analysis the study suggested that the use of fluoroquinolones during pregnancy may not be a major risk factor to the foetus.

  7. New fluoroquinolones: a class of potent antibiotics.

    PubMed

    De Souza, Marcus Vinícius Nora

    2005-11-01

    The discovery of antibiotics opened a new era in the treatment against several pathogenic microorganisms that can disable or kill humans. The appearance of the fluoroquinolones (based on nalidixic acid, 4-quinolone-3-carboxylates), in the early 1980's, gave a new impetus in the treatment of infectious diseases. Despite these favourable properties, the earlier fluoroquinolones had limited potency against some clinically important organisms, especially Gram-positive pathogens so that the development of resistance to these organisms has become a serious problem. Thus the development of new fluoroquinolones with a better pharmacokinetic profile, potency, broad spectrum of activity, solubility, prolonged serum half-life and oral and parenteral routes of administration has been a major focus on recent research. The increasing interest in this class led me to review the promising new fluoroquinolones in clinical trials.

  8. Impacts of a Discussion-Based Academic Language Program on Classroom Interactions in 4th through 7th Grades

    ERIC Educational Resources Information Center

    LaRusso, Maria; Jones, Stephanie M.; Kim, Ha Yeon; Kim, James; Donovan, Suzanne; Snow, Catherine

    2016-01-01

    This paper presents an exploratory analysis of treatment-control differences in the quality of classroom interactions in 4th through 7th grade urban classrooms. Word Generation (WG) is a research-based academic language program for middle school students designed to teach novel vocabulary and literacy through language arts, math, science, and…

  9. Fluoroquinolone-Resistant Enteric Bacteria in Sub-Saharan Africa: Clones, Implications and Research Needs

    PubMed Central

    Chattaway, Marie A.; Aboderin, Aaron O.; Fashae, Kayode; Okoro, Chinyere K.; Opintan, Japheth A.; Okeke, Iruka N.

    2016-01-01

    Fluoroquinolones came into widespread use in African countries in the early 2000s, after patents for the first generation of these drugs expired. By that time, quinolone antibacterial agents had been used intensively worldwide and resistant lineages of many bacterial species had evolved. We sought to understand which Gram negative enteric pandemic lineages have been reported from Africa, as well as the nature and transmission of any indigenous resistant clones. A systematic review of articles indexed in the Medline and AJOL literature databases was conducted. We report on the findings of 43 eligible studies documenting local or pandemic fluoroquinolone-resistant enteric clones in sub-Sahara African countries. Most reports are of invasive non-typhoidal Salmonella and Escherichia coli lineages and there have been three reports of cholera outbreaks caused by fluoroquinolone-resistant Vibrio cholerae O1. Fluoroquinolone-resistant clones have also been reported from commensals and animal isolates but there are few data for non-Enterobacteriaceae and almost none for difficult-to-culture Campylobacter spp. Fluoroquinolone-resistant lineages identified in African countries were universally resistant to multiple other classes of antibacterial agents. Although as many as 972 non-duplicate articles refer to fluoroquinolone resistance in enteric bacteria from Africa, most do not report on subtypes and therefore information on the epidemiology of fluoroquinolone-resistant clones is available from only a handful of countries in the subcontinent. When resistance is reported, resistance mechanisms and lineage information is rarely investigated. Insufficient attention has been given to molecular and sequence-based methods necessary for identifying and tracking resistant clones in Africa and more research is needed in this area. PMID:27148238

  10. Special Issue: 4th International Workshop on Space Radiation (IWSRR)

    NASA Technical Reports Server (NTRS)

    Cucinotta, Francis A.

    2007-01-01

    This special issue of the journal "Radiation and Environmental Biophysics" contains 20 peer-reviewed papers contributed by leading space radiation researcher's world-wide attending the 4th IWSRR. Manuscripts cover a broad range of topics ranging from radiation environments and transport in shielding and planetary surfaces to new results in understanding the biological effects of protons and high-charge and energy (HZE) nuclei on the risk of cancer, and degenerative diseases such as central nervous system effects, heart disease, and cataracts. The issue provides a snapshot of the state-of-the-art of the research in this field, demonstrating both the important results gathered in the past few years with experiments at accelerators, and the need for more research to quantify the risk and develop countermeasures.

  11. The Epilepsy Foundation's 4th Biennial Epilepsy Pipeline Update Conference.

    PubMed

    French, Jacqueline A; Schachter, Steven C; Sirven, Joseph; Porter, Roger

    2015-05-01

    On June 5 and 6, 2014, the Epilepsy Foundation held its 4th Biennial Epilepsy Pipeline Update Conference, an initiative of the Epilepsy Therapy Project, which showcased the most promising epilepsy innovations from health-care companies and academic laboratories dedicated to pioneering and advancing drugs, biologics, technologies, devices, and diagnostics for epilepsy. Speakers and attendees included emerging biotech and medical technology companies, major pharmaceutical and device companies, as well as investigators and innovators at the cutting-edge of epilepsy. The program included panel discussions on collaboration between small and large companies, how to get products in need of funding to the marketplace, who is currently funding epilepsy and CNS innovation, and how the NIH facilitates early-stage drug development. Finally, the conference featured the third annual "Shark Tank" competition. The presentations are summarized in this paper, which is followed by a compilation of the meeting poster abstracts. PMID:25922152

  12. Overexpression of Salmonella enterica serovar Typhi recA gene confers fluoroquinolone resistance in Escherichia coli DH5α.

    PubMed

    Yassien, M A M; Elfaky, M A

    2015-11-01

    A spontaneous fluoroquinolone-resistant mutant (STM1) was isolated from its parent Salmonella enterica serovar Typhi (S. Typhi) clinical isolate. Unlike its parent isolate, this mutant has selective resistance to fluoroquinolones without any change in its sensitivity to various other antibiotics. DNA gyrase assays revealed that the fluoroquinolone resistance phenotype of the STM1 mutant did not result from alteration of the fluoroquinolone sensitivity of the DNA gyrase isolated from it. To study the mechanism of fluoroquinolone resistance, a genomic library from the STM1 mutant was constructed in Escherichia coli DH5α and two recombinant plasmids were obtained. Only one of these plasmids (STM1-A) conferred the selective fluoroquinolone resistance phenotype to E. coli DH5α. The chromosomal insert from STM1-A, digested with EcoRI and HindIII restriction endonucleases, produced two DNA fragments and these were cloned separately into pUC19 thereby generating two new plasmids, STM1-A1 and STM1-A2. Only STM1-A1 conferred the selective fluoroquinolone resistance phenotype to E. coli DH5α. Sequence and subcloning analyses of STM1-A1 showed the presence of an intact RecA open reading frame. Unlike that of the wild-type E. coli DH5α, protein analysis of a crude STM1-A1 extract showed overexpression of a 40 kDa protein. Western blotting confirmed the 40 kDa protein band to be RecA. When a RecA PCR product was cloned into pGEM-T and introduced into E. coli DH5α, the STM1-A11 subclone retained fluoroquinolone resistance. These results suggest that overexpression of RecA causes selective fluoroquinolone resistance in E. coli DH5α. PMID:26375447

  13. Fluoroquinolone-induced gene transfer in multidrug-resistant Salmonella

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fluoroquinolones are broad spectrum antibiotics that inhibit bacterial DNA gyrase and topoisomerase activity. Bacterial exposure to fluoroquinolones can cause DNA damage and induce a bacterial SOS response to stimulate repair of damaged DNA. Certain prophages (integrated in bacterial chromosomes) ...

  14. Methods for analysis of fluoroquinolones in biological fluids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Methods for analysis of 10 selected fluoroquinolone antibiotics in biological fluids are reviewed. Approaches for sample preparation, detection methods, limits of detection and quantitation and recovery information are provided for both single analyte and multi-analyte fluoroquinolone methods....

  15. 76 FR 37649 - Safety Zone; Northern California Annual Fireworks Events, July 4th Fireworks Display

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-28

    ... SECURITY Coast Guard 33 CFR Part 165 Safety Zone; Northern California Annual Fireworks Events, July 4th Fireworks Display AGENCY: Coast Guard, DHS. ACTION: Notice of enforcement of regulation. SUMMARY: The Coast Guard will enforce safety zone for the annual July 4th Fireworks Display (Tahoe City 4th of...

  16. PREFACE: 4th International Symposium on Functional Materials (ISFM2011)

    NASA Astrophysics Data System (ADS)

    Yin, Shu; Sekino, Tohru; Tanaka, Shun-ichiro; Sato, Tsugio; Lu, Li; Xue, Dongfeng

    2012-01-01

    The 4th International Symposium on Functional Materials (ISFM2011) was held in Sendai, Japan, on 2-6 August 2011. This Special Issue of Journal of Physics: Conference Series (JPCS) consists of partial manuscripts which were presented at ISFM2011. Advanced materials have experienced a dramatic increase in demand for research, development and applications. The aim of the International Symposium on Functional Materials (ISFM) was to provide an overview of the present status with historical background and to foresee future trends in the field of functional materials. The 4th symposium, ISFM 2011, covered a wide variety of topics within state-of-the-art advanced materials science and technology, and focused especially on four major categories including: Environmental Materials, Electronic Materials, Energy Materials and Biomedical Materials. As you know, a massive earthquake and the Tsunami that followed occurred near the Tohoku region on 11 March 2011. After the earthquake, although there were many difficulties in continuing to organize the symposium, we received warm encouragement from many researchers and societies, especially from the members of the International Advisory Committee and Organizing Committee, so that ISFM2011 could be held on schedule. We are honored that ISFM2011 was the first formal international academic conference held in the Tohoku area of Japan after the 11 March earthquake. About 140 participants from 14 countries took part in the ISFM2011 symposium, which included five plenary talks by world-leading scientists, 32 invited talks, and many oral and poster presentations. We are delighted to see that many researchers are interested in the synthesis and the properties as well as the applications of functional materials. Many fruitful and exciting research achievements were presented in the symposium. We believe that this symposium provided a good chance for scientists to communicate and exchange opinions with each other. We would also like to

  17. Managing haemophilia for life: 4th Haemophilia Global Summit.

    PubMed

    Astermark, J; Dolan, G; Hilberg, T; Jiménez-Yuste, V; Laffan, M; Lassila, R; Lobet, S; Martinoli, C; Perno, C-F

    2014-07-01

    The 4th Haemophilia Global Summit was held in Potsdam, Germany, in September 2013 and brought together an international faculty of haemophilia experts and delegates from multidisciplinary backgrounds. The programme was designed by an independent Scientific Steering Committee of haemophilia experts and explored global perspectives in haemophilia care, discussing practical approaches to the optimal management of haemophilia now and in the future. The topics outlined in this supplement were selected by the Scientific Steering Committee for their relevance and potential to influence haemophilia care globally. In this supplement from the meeting, Jan Astermark reviews current understanding of risk factors for the development of inhibitory antibodies and discusses whether this risk can be modulated and minimized. Factors key to the improvement of joint health in people with haemophilia are explored, with Carlo Martinoli and Víctor Jiménez-Yuste discussing the utility of ultrasound for the early detection of haemophilic arthropathy. Other aspects of care necessary for the prevention and management of joint disease in people with haemophilia are outlined by Thomas Hilberg and Sébastian Lobet, who highlight the therapeutic benefits of physiotherapy and sports therapy. Riitta Lassila and Carlo-Federico Perno describe current knowledge surrounding the risk of transmission of infectious agents via clotting factor concentrates. Finally, different types of extended half-life technology are evaluated by Mike Laffan, with a focus on the practicalities and challenges associated with these products.

  18. European Code against Cancer 4th Edition: Diet and cancer.

    PubMed

    Norat, Teresa; Scoccianti, Chiara; Boutron-Ruault, Marie-Christine; Anderson, Annie; Berrino, Franco; Cecchini, Michele; Espina, Carolina; Key, Tim; Leitzmann, Michael; Powers, Hilary; Wiseman, Martin; Romieu, Isabelle

    2015-12-01

    Lifestyle factors, including diet, have long been recognised as potentially important determinants of cancer risk. In addition to the significant role diet plays in affecting body fatness, a risk factor for several cancers, experimental studies have indicated that diet may influence the cancer process in several ways. Prospective studies have shown that dietary patterns characterised by higher intakes of fruits, vegetables, and whole-grain foods, and lower intakes of red and processed meats and salt, are related to reduced risks of death and cancer, and that a healthy diet can improve overall survival after diagnosis of breast and colorectal cancers. There is evidence that high intakes of fruit and vegetables may reduce the risk of cancers of the aerodigestive tract, and the evidence that dietary fibre protects against colorectal cancer is convincing. Red and processed meats increase the risk of colorectal cancer. Diets rich in high-calorie foods, such as fatty and sugary foods, may lead to increased calorie intake, thereby promoting obesity and leading to an increased risk of cancer. There is some evidence that sugary drinks are related to an increased risk of pancreatic cancer. Taking this evidence into account, the 4th edition of the European Code against Cancer recommends that people have a healthy diet to reduce their risk of cancer: they should eat plenty of whole grains, pulses, vegetables and fruits; limit high-calorie foods (foods high in sugar or fat); avoid sugary drinks and processed meat; and limit red meat and foods high in salt.

  19. European Code against Cancer 4th Edition: Diet and cancer.

    PubMed

    Norat, Teresa; Scoccianti, Chiara; Boutron-Ruault, Marie-Christine; Anderson, Annie; Berrino, Franco; Cecchini, Michele; Espina, Carolina; Key, Tim; Leitzmann, Michael; Powers, Hilary; Wiseman, Martin; Romieu, Isabelle

    2015-12-01

    Lifestyle factors, including diet, have long been recognised as potentially important determinants of cancer risk. In addition to the significant role diet plays in affecting body fatness, a risk factor for several cancers, experimental studies have indicated that diet may influence the cancer process in several ways. Prospective studies have shown that dietary patterns characterised by higher intakes of fruits, vegetables, and whole-grain foods, and lower intakes of red and processed meats and salt, are related to reduced risks of death and cancer, and that a healthy diet can improve overall survival after diagnosis of breast and colorectal cancers. There is evidence that high intakes of fruit and vegetables may reduce the risk of cancers of the aerodigestive tract, and the evidence that dietary fibre protects against colorectal cancer is convincing. Red and processed meats increase the risk of colorectal cancer. Diets rich in high-calorie foods, such as fatty and sugary foods, may lead to increased calorie intake, thereby promoting obesity and leading to an increased risk of cancer. There is some evidence that sugary drinks are related to an increased risk of pancreatic cancer. Taking this evidence into account, the 4th edition of the European Code against Cancer recommends that people have a healthy diet to reduce their risk of cancer: they should eat plenty of whole grains, pulses, vegetables and fruits; limit high-calorie foods (foods high in sugar or fat); avoid sugary drinks and processed meat; and limit red meat and foods high in salt. PMID:26164653

  20. Rapid evolution of fluoroquinolone-resistant Escherichia coli in Nigeria is temporally associated with fluoroquinolone use

    PubMed Central

    2011-01-01

    Background Antibiotic resistance has necessitated fluoroquinolone use but little is known about the selective forces and resistance trajectory in malaria-endemic settings, where selection from the antimalarial chloroquine for fluoroquinolone-resistant bacteria has been proposed. Methods Antimicrobial resistance was studied in fecal Escherichia coli isolates in a Nigerian community. Quinolone-resistance determining regions of gyrA and parC were sequenced in nalidixic acid resistant strains and horizontally-transmitted quinolone-resistance genes were sought by PCR. Antimicrobial prescription practices were compared with antimicrobial resistance rates over a period spanning three decades. Results Before 2005, quinolone resistance was limited to low-level nalixidic acid resistance in fewer than 4% of E. coli isolates. In 2005, the proportion of isolates demonstrating low-level quinolone resistance due to elevated efflux increased and high-level quinolone resistance and resistance to the fluoroquinolones appeared. Fluoroquinolone resistance was attributable to single nucleotide polymorphisms in quinolone target genes gyrA and/or parC. By 2009, 35 (34.5%) of isolates were quinolone non-susceptible with nine carrying gyrA and parC SNPs and six bearing identical qnrS1 alleles. The antimalarial chloroquine was heavily used throughout the entire period but E. coli with quinolone-specific resistance mechanisms were only detected in the final half decade, immediately following the introduction of the fluoroquinolone antibacterial ciprofloxacin. Conclusions Fluoroquinolones, and not chloroquine, appear to be the selective force for fluoroquinolone-resistant fecal E. coli in this setting. Rapid evolution to resistance following fluoroquinolone introduction points the need to implement resistant containment strategies when new antibacterials are introduced into resource-poor settings with high infectious disease burdens. PMID:22060770

  1. Do we need an intravenous fluoroquinolone?

    PubMed Central

    Maddix, D S; Warner, L

    1992-01-01

    Intravenous ciprofloxacin, the first parenteral fluoroquinolone available in this country, represents another class of antimicrobial agents from which physicians must choose when treating nosocomial infections. Fluoroquinolones are bactericidal antimicrobial agents that act by inhibiting DNA gyrase. They are active in vitro against most gram-negative bacteria and methicillin-susceptible staphylococci. Activity against anaerobic bacteria and streptococci is poor. The rapid development of bacterial resistance in centers with high quinolone usage is of great concern. Resistance develops most commonly in Pseudomonas aeruginosa and staphylococci. Resistance emerges most often when quinolones are used to treat chronic infections or in patients with poorly drained abscesses, necrotic tissue, or indwelling catheters. Clinical trials have shown ciprofloxacin to be as effective as ceftazidime in the treatment of infections caused by gram-negative bacteria. Although the overall frequency of side effects to fluoroquinolones is low, seizures and allergic reactions have been attributed to their use. Ciprofloxacin inhibits the metabolism of theophylline, and morbidity and death have been reported in patients taking the two drugs concomitantly. Parenteral fluoroquinolones should be reserved for the treatment of gram-negative bacterial infections in patients in whom standard agents cannot be used. PMID:1413744

  2. Results of 4th repeated levelling survey in Estonia

    NASA Astrophysics Data System (ADS)

    Kall, Tarmo; Torim, Ants; Jürma, Helju; Liibusk, Aive; Jürgenson, Harli

    2010-05-01

    Estonian precise levelling network consists of about 2000 km levelling lines and 1300 benchmarks. Three precise repeated levellings were carried out: in 1933-1943, 1948-1969 and 1970-1996. Three height systems have been realized: Tallinn Height System (unofficial system), Baltic Height System of 1951 and Baltic Height System of 1977 (BK77). Campaign of 4th repeated levelling was started at 2004 with goal to reconstruct the destroyed and damaged benchmarks, to realize the new height system and concept of integrated geodetic network. Reconstructed levelling network will consist of approximately 3000 km levelling lines and 2300 benchmarks. Digital level DiNi and NEDO invar code rod is used for levelling. Levellings carried out so far is characterized by high precision: levelling error calculated using levelling loops closing error is 0.23 mm/km. In the end of 2010 is planned to complete the levelling field work. After that the processing of the levelling data and the realization of the new height system will be implemented. Goal of the present study was to adjust the height differences of the latest repeated levelling and compare obtained benchmarks heights with previous ones. Method of the least squares and software SBG GEO 2005 was used for adjustment. Minimally constrained adjustment with one fixed benchmarks was used. Location of the benchmark was chosen in the area of minimal postglacial land uplift. Obtained benchmark heights are preliminary because no rod calibration, refraction etc. corrections were added yet to field height differences. Therefore obtained heights are not realization of the new height system. Still obtained heights can be used for example for improving of Estonian geoid model. In comparison between new and old benchmark heights, SE-NW directional pattern of postglacial land uplift appeared as expected.

  3. European Code against Cancer, 4th Edition: Cancer screening.

    PubMed

    Armaroli, Paola; Villain, Patricia; Suonio, Eero; Almonte, Maribel; Anttila, Ahti; Atkin, Wendy S; Dean, Peter B; de Koning, Harry J; Dillner, Lena; Herrero, Rolando; Kuipers, Ernst J; Lansdorp-Vogelaar, Iris; Minozzi, Silvia; Paci, Eugenio; Regula, Jaroslaw; Törnberg, Sven; Segnan, Nereo

    2015-12-01

    In order to update the previous version of the European Code against Cancer and formulate evidence-based recommendations, a systematic search of the literature was performed according to the methodology agreed by the Code Working Groups. Based on the review, the 4th edition of the European Code against Cancer recommends: "Take part in organized cancer screening programmes for: Bowel cancer (men and women); Breast cancer (women); Cervical cancer (women)." Organized screening programs are preferable because they provide better conditions to ensure that the Guidelines for Quality Assurance in Screening are followed in order to achieve the greatest benefit with the least harm. Screening is recommended only for those cancers where a demonstrated life-saving effect substantially outweighs the potential harm of examining very large numbers of people who may otherwise never have, or suffer from, these cancers, and when an adequate quality of the screening is achieved. EU citizens are recommended to participate in cancer screening each time an invitation from the national or regional screening program is received and after having read the information materials provided and carefully considered the potential benefits and harms of screening. Screening programs in the European Union vary with respect to the age groups invited and to the interval between invitations, depending on each country's cancer burden, local resources, and the type of screening test used For colorectal cancer, most programs in the EU invite men and women starting at the age of 50-60 years, and from then on every 2 years if the screening test is the guaiac-based fecal occult blood test or fecal immunochemical test, or every 10 years or more if the screening test is flexible sigmoidoscopy or total colonoscopy. Most programs continue sending invitations to screening up to the age of 70-75 years. For breast cancer, most programs in the EU invite women starting at the age of 50 years, and not before the age

  4. European Code against Cancer, 4th Edition: Cancer screening.

    PubMed

    Armaroli, Paola; Villain, Patricia; Suonio, Eero; Almonte, Maribel; Anttila, Ahti; Atkin, Wendy S; Dean, Peter B; de Koning, Harry J; Dillner, Lena; Herrero, Rolando; Kuipers, Ernst J; Lansdorp-Vogelaar, Iris; Minozzi, Silvia; Paci, Eugenio; Regula, Jaroslaw; Törnberg, Sven; Segnan, Nereo

    2015-12-01

    In order to update the previous version of the European Code against Cancer and formulate evidence-based recommendations, a systematic search of the literature was performed according to the methodology agreed by the Code Working Groups. Based on the review, the 4th edition of the European Code against Cancer recommends: "Take part in organized cancer screening programmes for: Bowel cancer (men and women); Breast cancer (women); Cervical cancer (women)." Organized screening programs are preferable because they provide better conditions to ensure that the Guidelines for Quality Assurance in Screening are followed in order to achieve the greatest benefit with the least harm. Screening is recommended only for those cancers where a demonstrated life-saving effect substantially outweighs the potential harm of examining very large numbers of people who may otherwise never have, or suffer from, these cancers, and when an adequate quality of the screening is achieved. EU citizens are recommended to participate in cancer screening each time an invitation from the national or regional screening program is received and after having read the information materials provided and carefully considered the potential benefits and harms of screening. Screening programs in the European Union vary with respect to the age groups invited and to the interval between invitations, depending on each country's cancer burden, local resources, and the type of screening test used For colorectal cancer, most programs in the EU invite men and women starting at the age of 50-60 years, and from then on every 2 years if the screening test is the guaiac-based fecal occult blood test or fecal immunochemical test, or every 10 years or more if the screening test is flexible sigmoidoscopy or total colonoscopy. Most programs continue sending invitations to screening up to the age of 70-75 years. For breast cancer, most programs in the EU invite women starting at the age of 50 years, and not before the age

  5. DNA repair inhibition by UVA photoactivated fluoroquinolones and vemurafenib

    PubMed Central

    Peacock, Matthew; Brem, Reto; Macpherson, Peter; Karran, Peter

    2014-01-01

    Cutaneous photosensitization is a common side effect of drug treatment and can be associated with an increased skin cancer risk. The immunosuppressant azathioprine, the fluoroquinolone antibiotics and vemurafenib—a BRAF inhibitor used to treat metastatic melanoma—are all recognized clinical photosensitizers. We have compared the effects of UVA radiation on cultured human cells treated with 6-thioguanine (6-TG, a DNA-embedded azathioprine surrogate), the fluoroquinolones ciprofloxacin and ofloxacin and vemurafenib. Despite widely different structures and modes of action, each of these drugs potentiated UVA cytotoxicity. UVA photoactivation of 6-TG, ciprofloxacin and ofloxacin was associated with the generation of singlet oxygen that caused extensive protein oxidation. In particular, these treatments were associated with damage to DNA repair proteins that reduced the efficiency of nucleotide excision repair. Although vemurafenib was also highly phototoxic to cultured cells, its effects were less dependent on singlet oxygen. Highly toxic combinations of vemurafenib and UVA caused little protein carbonylation but were nevertheless inhibitory to nucleotide excision repair. Thus, for three different classes of drugs, photosensitization by at least two distinct mechanisms is associated with reduced protection against potentially mutagenic and carcinogenic DNA damage. PMID:25414333

  6. Fluoroquinolone Resistance among Clonal Complex 1 Group B Streptococcus Strains.

    PubMed

    Neemuchwala, Alefiya; Teatero, Sarah; Patel, Samir N; Fittipaldi, Nahuel

    2016-01-01

    Fluoroquinolone resistance in group B Streptococcus is increasingly being reported worldwide. Here, we correlated fluoroquinolone resistance with mutations in gyrA, gyrB, parC, and parE genes, identified by mining whole-genome sequencing (WGS) data of 190 clonal complex 1 group B Streptococcus strains recovered from patients with invasive diseases in North America. We report a high prevalence of fluoroquinolone resistance (12%) among GBS strains in our collection. Our approach is the first step towards accurate prediction of fluoroquinolone resistance from WGS data in this opportunistic pathogen. PMID:27559344

  7. Fluoroquinolone Resistance among Clonal Complex 1 Group B Streptococcus Strains

    PubMed Central

    Teatero, Sarah; Patel, Samir N.

    2016-01-01

    Fluoroquinolone resistance in group B Streptococcus is increasingly being reported worldwide. Here, we correlated fluoroquinolone resistance with mutations in gyrA, gyrB, parC, and parE genes, identified by mining whole-genome sequencing (WGS) data of 190 clonal complex 1 group B Streptococcus strains recovered from patients with invasive diseases in North America. We report a high prevalence of fluoroquinolone resistance (12%) among GBS strains in our collection. Our approach is the first step towards accurate prediction of fluoroquinolone resistance from WGS data in this opportunistic pathogen. PMID:27559344

  8. 75 FR 35649 - Safety Zone; Northern California Annual Fireworks Events, July 4th Fireworks Display

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-23

    ... SECURITY Coast Guard 33 CFR Part 165 Safety Zone; Northern California Annual Fireworks Events, July 4th Fireworks Display AGENCY: Coast Guard, DHS. ACTION: Notice of enforcement of regulation. SUMMARY: The Coast Guard will enforce the Tahoe City 4th of July Fireworks Display safety zone, from 9 a.m. through 10...

  9. 75 FR 26157 - Safety Zone; Reedville July 4th Celebration, Cockrell's Creek, Reedville, VA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-11

    ... Federal Register (73 FR 3316). Public Meeting We do not now plan to hold a public meeting. But you may... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Reedville July 4th Celebration, Cockrell's..., VA in support of the Reedville July 4th Celebration event. This action is intended to restrict...

  10. Science Content Courses: Workshop in Food Chemistry for 4th Grade School Teachers

    ERIC Educational Resources Information Center

    Chaiyapechara, S.; Dong, F. M.

    2004-01-01

    A science content course in food chemistry was offered as a 4-day summer workshop from 1999 to 2001 to 4th grade school teachers in the Seattle School District. The objectives of the workshop were to increase the teachers' knowledge of food science, to perform simple experiments that could be used in the 4th grade classroom, and to help the…

  11. The school nutrition program's role in weight management of 4th grade elementary students

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We are attempting to uncover the school nutrition program's role in weight management of 4th grade elementary students. Data was collected within a time frame for the food frequency questionnaire (FFQ) set at two months at the WT Cheney Elementary School and South Wood Elementary for 4th grade stud...

  12. The Effects of Cooperative Learning Strategies on Vocabulary Skills of 4th Grade Students

    ERIC Educational Resources Information Center

    Bilen, Didem; Tavil, Zekiye Müge

    2015-01-01

    This study was carried out to investigate the effects of cooperative learning strategies on the vocabulary skills of 4th grade students. The study was also designed to ascertain the attitudes of the students in the experimental group towards cooperative learning. Out of 96 4th grade students enrolled in the private school where the study took…

  13. Efficient recovery of fluoroquinolone-susceptible and fluoroquinolone-resistant Escherichia coli strains from frozen samples.

    PubMed

    Lautenbach, Ebbing; Santana, Evelyn; Lee, Abby; Tolomeo, Pam; Black, Nicole; Babson, Andrew; Perencevich, Eli N; Harris, Anthony D; Smith, Catherine A; Maslow, Joel

    2008-04-01

    We assessed the rate of recovery of fluoroquinolone-resistant and fluoroquinolone-susceptible Escherichia coli isolates from culture of frozen perirectal swab samples compared with the results for culture of the same specimen before freezing. Recovery rates for these 2 classes of E. coli were 91% and 83%, respectively. The majority of distinct strains recovered from the initial sample were also recovered from the frozen sample. The strains that were not recovered were typically present only in low numbers in the initial sample. These findings emphasize the utility of frozen surveillance samples. PMID:18279070

  14. The 1992 4th NASA SERC Symposium on VLSI Design

    NASA Technical Reports Server (NTRS)

    Whitaker, Sterling R.

    1992-01-01

    Papers from the fourth annual NASA Symposium on VLSI Design, co-sponsored by the IEEE, are presented. Each year this symposium is organized by the NASA Space Engineering Research Center (SERC) at the University of Idaho and is held in conjunction with a quarterly meeting of the NASA Data System Technology Working Group (DSTWG). One task of the DSTWG is to develop new electronic technologies that will meet next generation electronic data system needs. The symposium provides insights into developments in VLSI and digital systems which can be used to increase data systems performance. The NASA SERC is proud to offer, at its fourth symposium on VLSI design, presentations by an outstanding set of individuals from national laboratories, the electronics industry, and universities. These speakers share insights into next generation advances that will serve as a basis for future VLSI design.

  15. Susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada.

    PubMed

    Patel, Samir N; McGeer, Allison; Melano, Roberto; Tyrrell, Gregory J; Green, Karen; Pillai, Dylan R; Low, Donald E

    2011-08-01

    Ciprofloxacin, the first fluoroquinolone to be used to treat lower respiratory tract infections (LRTI), demonstrates poor potency against Streptococcus pneumoniae, and its use has been associated with the emergence of resistance. During the last decade, fluoroquinolones with enhanced in vitro activity against S. pneumoniae have replaced ciprofloxacin for the treatment of LRTI. Here, we analyzed the impact of more active fluoroquinolone usage on pneumococci by examining the fluoroquinolone usage, prevalence of fluoroquinolone resistance, and mutations in the genes that encode the major target sites for the fluoroquinolones (gyrA and parC) in pneumococcal isolates collected in Canada-wide surveillance. A total of 26,081 isolates were collected between 1998 and 2009. During this time period, total per capita outpatient use of fluoroquinolones increased from 64 to 96 prescriptions per 1,000 persons per year. The proportion of prescriptions for respiratory tract infection that were for fluoroquinolones increased from 5.9% to 10.7%, but the distribution changed: the proportion of prescriptions for ciprofloxacin decreased from 5.3% to 0.5%, and those for levofloxacin or moxifloxacin increased from 1.5% in 1999 to 5.9% in 2009. The prevalence of ciprofloxacin resistance (MIC ≥ 4 μg/ml), levofloxacin resistance, and moxifloxacin resistance remained unchanged at <2%. Multivariable analyses showed that prevalence of mutations known to be associated with reduced susceptibility to fluoroquinolones did not change during the surveillance period. If fluoroquinolone therapy is required, the preferential use of fluoroquinolones with enhanced pneumococcal activity to treat pneumococcal infections may slow the emergence of resistance in S. pneumoniae.

  16. Susceptibility of Streptococcus pneumoniae to Fluoroquinolones in Canada▿

    PubMed Central

    Patel, Samir N.; McGeer, Allison; Melano, Roberto; Tyrrell, Gregory J.; Green, Karen; Pillai, Dylan R.; Low, Donald E.

    2011-01-01

    Ciprofloxacin, the first fluoroquinolone to be used to treat lower respiratory tract infections (LRTI), demonstrates poor potency against Streptococcus pneumoniae, and its use has been associated with the emergence of resistance. During the last decade, fluoroquinolones with enhanced in vitro activity against S. pneumoniae have replaced ciprofloxacin for the treatment of LRTI. Here, we analyzed the impact of more active fluoroquinolone usage on pneumococci by examining the fluoroquinolone usage, prevalence of fluoroquinolone resistance, and mutations in the genes that encode the major target sites for the fluoroquinolones (gyrA and parC) in pneumococcal isolates collected in Canada-wide surveillance. A total of 26,081 isolates were collected between 1998 and 2009. During this time period, total per capita outpatient use of fluoroquinolones increased from 64 to 96 prescriptions per 1,000 persons per year. The proportion of prescriptions for respiratory tract infection that were for fluoroquinolones increased from 5.9% to 10.7%, but the distribution changed: the proportion of prescriptions for ciprofloxacin decreased from 5.3% to 0.5%, and those for levofloxacin or moxifloxacin increased from 1.5% in 1999 to 5.9% in 2009. The prevalence of ciprofloxacin resistance (MIC ≥ 4 μg/ml), levofloxacin resistance, and moxifloxacin resistance remained unchanged at <2%. Multivariable analyses showed that prevalence of mutations known to be associated with reduced susceptibility to fluoroquinolones did not change during the surveillance period. If fluoroquinolone therapy is required, the preferential use of fluoroquinolones with enhanced pneumococcal activity to treat pneumococcal infections may slow the emergence of resistance in S. pneumoniae. PMID:21628545

  17. Global Fluoroquinolone Resistance Epidemiology and Implictions for Clinical Use

    PubMed Central

    Dalhoff, Axel

    2012-01-01

    This paper on the fluoroquinolone resistance epidemiology stratifies the data according to the different prescription patterns by either primary or tertiary caregivers and by indication. Global surveillance studies demonstrate that fluoroquinolone resistance rates increased in the past years in almost all bacterial species except S. pneumoniae and H. influenzae, causing community-acquired respiratory tract infections. However, 10 to 30% of these isolates harbored first-step mutations conferring low level fluoroquinolone resistance. Fluoroquinolone resistance increased in Enterobacteriaceae causing community acquired or healthcare associated urinary tract infections and intraabdominal infections, exceeding 50% in some parts of the world, particularly in Asia. One to two-thirds of Enterobacteriaceae producing extended spectrum β-lactamases were fluoroquinolone resistant too. Furthermore, fluoroquinolones select for methicillin resistance in Staphylococci. Neisseria gonorrhoeae acquired fluoroquinolone resistance rapidly; actual resistance rates are highly variable and can be as high as almost 100%, particularly in Asia, whereas resistance rates in Europe and North America range from <10% in rural areas to >30% in established sexual networks. In general, the continued increase in fluoroquinolone resistance affects patient management and necessitates changes in some guidelines, for example, treatment of urinary tract, intra-abdominal, skin and skin structure infections, and traveller's diarrhea, or even precludes the use in indications like sexually transmitted diseases and enteric fever. PMID:23097666

  18. Pradofloxacin: a novel veterinary fluoroquinolone for treatment of bacterial infections in cats.

    PubMed

    Sykes, Jane E; Blondeau, Joseph M

    2014-08-01

    Pradofloxacin is a novel third-generation oral veterinary fluoroquinolone with activity against Gram-positive aerobic bacteria and anaerobes (lower minimum inhibitory concentrations in vitro). It also has activity against other bacterial species, including Bartonella henselae, Pasteurella multocida, Bordetella bronchiseptica, extra-intestinal Escherichia coli, and some mycobacterial species. This review focuses on the current knowledge of the mechanism of action, adverse effects, clinical applications, and pharmacokinetic/pharmacodynamic properties of pradofloxacin in cats. PMID:24997792

  19. 4th Annual DOE-ERSP PI Meeting: Abstracts

    SciTech Connect

    Hazen, Terry C.

    2009-03-01

    This contains abstracts from the 2009 Annual Environmental Remediation Sciences Program (ERSP) Principal Investigators (PI) Meeting. The ERSP seeks to advance fundamental science to understand, predict, and mitigate the impacts of environmental contamination from past nuclear weapons production and provide a scientific basis for the long-term stewardship of nuclear waste disposal. These ambitious goals cannot be achieved by any one project alone. Therefore, ERSP funds a combination of research programs at the DOE national laboratories, individual projects at universities and federal agencies, and large long(er)-term field site research. Integration of these activities to advance the ERSP goals is a constant challenge, but made significantly simpler by bringing together all funded ERSP researchers once a year to discuss the very latest research results. It is at these meetings where new ideas and/or scientific advancements in support of ERSP goals can be discussed and openly debated among all PIs in the program. The ERSP thrives, in part, on the new ideas, concepts, scientific connections, and collaborations generated as a result of these meetings. The annual PI Meeting is very much a working meeting with three major goals: (1) to provide opportunities for scientific interaction among the ERSP scientists, a critical element for the program; (2) to provide the ERSP program staff with an opportunity to evaluate the progress of each program and project; and (3) to showcase the ERSP to interested parties within DOE and within other federal agencies In addition to program managers from within OBER, there will be representatives from other offices within DOE and other federal agencies in attandance at the meeting.

  20. 4th floor sacking deck looking east from 1945 elevator to ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4th floor sacking deck looking east from 1945 elevator to 1913 elevator indicating spout used to load bulk grain into rail cars - Stewart Company Grain Elevator, 16 West Carson Street, Pittsburgh, Allegheny County, PA

  1. 16. 4th floor roof, view west, north side of setback ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    16. 4th floor roof, view west, north side of setback to left and delivery stair bulkhead to right - Sheffield Farms Milk Plant, 1075 Webster Avenue (southwest corner of 166th Street), Bronx, Bronx County, NY

  2. Physics Computing '92: Proceedings of the 4th International Conference

    NASA Astrophysics Data System (ADS)

    de Groot, Robert A.; Nadrchal, Jaroslav

    1993-04-01

    * Ordered Particle Simulations for Serial and MIMD Parallel Computers * "NOLP" -- Program Package for Laser Plasma Nonlinear Optics * Algorithms to Solve Nonlinear Least Square Problems * Distribution of Hydrogen Atoms in Pd-H Computed by Molecular Dynamics * A Ray Tracing of Optical System for Protein Crystallography Beamline at Storage Ring-SIBERIA-2 * Vibrational Properties of a Pseudobinary Linear Chain with Correlated Substitutional Disorder * Application of the Software Package Mathematica in Generalized Master Equation Method * Linelist: An Interactive Program for Analysing Beam-foil Spectra * GROMACS: A Parallel Computer for Molecular Dynamics Simulations * GROMACS Method of Virial Calculation Using a Single Sum * The Interactive Program for the Solution of the Laplace Equation with the Elimination of Singularities for Boundary Functions * Random-Number Generators: Testing Procedures and Comparison of RNG Algorithms * Micro-TOPIC: A Tokamak Plasma Impurities Code * Rotational Molecular Scattering Calculations * Orthonormal Polynomial Method for Calibrating of Cryogenic Temperature Sensors * Frame-based System Representing Basis of Physics * The Role of Massively Data-parallel Computers in Large Scale Molecular Dynamics Simulations * Short-range Molecular Dynamics on a Network of Processors and Workstations * An Algorithm for Higher-order Perturbation Theory in Radiative Transfer Computations * Hydrostochastics: The Master Equation Formulation of Fluid Dynamics * HPP Lattice Gas on Transputers and Networked Workstations * Study on the Hysteresis Cycle Simulation Using Modeling with Different Functions on Intervals * Refined Pruning Techniques for Feed-forward Neural Networks * Random Walk Simulation of the Motion of Transient Charges in Photoconductors * The Optical Hysteresis in Hydrogenated Amorphous Silicon * Diffusion Monte Carlo Analysis of Modern Interatomic Potentials for He * A Parallel Strategy for Molecular Dynamics Simulations of Polar Liquids on

  3. Physics Computing '92: Proceedings of the 4th International Conference

    NASA Astrophysics Data System (ADS)

    de Groot, Robert A.; Nadrchal, Jaroslav

    1993-04-01

    * Ordered Particle Simulations for Serial and MIMD Parallel Computers * "NOLP" -- Program Package for Laser Plasma Nonlinear Optics * Algorithms to Solve Nonlinear Least Square Problems * Distribution of Hydrogen Atoms in Pd-H Computed by Molecular Dynamics * A Ray Tracing of Optical System for Protein Crystallography Beamline at Storage Ring-SIBERIA-2 * Vibrational Properties of a Pseudobinary Linear Chain with Correlated Substitutional Disorder * Application of the Software Package Mathematica in Generalized Master Equation Method * Linelist: An Interactive Program for Analysing Beam-foil Spectra * GROMACS: A Parallel Computer for Molecular Dynamics Simulations * GROMACS Method of Virial Calculation Using a Single Sum * The Interactive Program for the Solution of the Laplace Equation with the Elimination of Singularities for Boundary Functions * Random-Number Generators: Testing Procedures and Comparison of RNG Algorithms * Micro-TOPIC: A Tokamak Plasma Impurities Code * Rotational Molecular Scattering Calculations * Orthonormal Polynomial Method for Calibrating of Cryogenic Temperature Sensors * Frame-based System Representing Basis of Physics * The Role of Massively Data-parallel Computers in Large Scale Molecular Dynamics Simulations * Short-range Molecular Dynamics on a Network of Processors and Workstations * An Algorithm for Higher-order Perturbation Theory in Radiative Transfer Computations * Hydrostochastics: The Master Equation Formulation of Fluid Dynamics * HPP Lattice Gas on Transputers and Networked Workstations * Study on the Hysteresis Cycle Simulation Using Modeling with Different Functions on Intervals * Refined Pruning Techniques for Feed-forward Neural Networks * Random Walk Simulation of the Motion of Transient Charges in Photoconductors * The Optical Hysteresis in Hydrogenated Amorphous Silicon * Diffusion Monte Carlo Analysis of Modern Interatomic Potentials for He * A Parallel Strategy for Molecular Dynamics Simulations of Polar Liquids on

  4. 75 FR 38721 - Safety Zone; Munising 4th of July Fireworks, South Bay, Lake Superior, Munising, MI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-06

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Munising 4th of July Fireworks, South Bay... is intended to restrict vessels from a portion of South Bay during the Munising 4th of July Fireworks... from hazards associated with the Munising 4th of July Fireworks display. Based on the explosive...

  5. 75 FR 34369 - Safety Zones; City of Chicago's July 4th Celebration Fireworks, Lake Michigan, Chicago, IL

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-17

    ... Chicago's July 4th Celebration Fireworks, Chicago, Illinois in the Federal Register (75 FR 22330). We... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zones; City of Chicago's July 4th Celebration... associated with the City of Chicago's July 4th Celebration Fireworks. The Captain of the Port, Sector...

  6. 75 FR 38718 - Safety Zone; Sault Sainte Marie 4th of July Fireworks, St. Mary's River, Sault Sainte Marie, MI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-06

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Sault Sainte Marie 4th of July Fireworks... the Sault Sainte Marie 4th of July Fireworks display, July ] 4, 2010. This temporary safety zone is... with the Sault Sainte Marie 4th of July Fireworks display. The fireworks display is planned to...

  7. Collaborative study for the establishment of the 4(th) International Standard for Streptomycin.

    PubMed

    Jorajuria, S; Raphalen, C; Dujardin, V; Daas, A

    2015-01-01

    An international collaborative study was organised to establish the 4(th) World Health Organization (WHO) International Standard (IS) for Streptomycin. Fourteen laboratories from different countries participated. Potencies of the candidate material were estimated by microbiological assays with sensitive micro-organisms. To ensure continuity between consecutive batches, the 3(rd) IS for Streptomycin was used as a reference. Based on the results of the study, the 4(th) IS for Streptomycin was adopted at the meeting of the WHO Expert Committee for Biological Standardization (ECBS) in 2015 with an assigned potency of 76 000 International Units (IU) per vial. The 4(th) IS for Streptomycin is available from the European Directorate for the Quality of Medicines & HealthCare (EDQM).

  8. Porting LEON3FT/GRLIB to 4th Generation Flash-Based Devices

    NASA Astrophysics Data System (ADS)

    Andersson, Jan; Habinc, Sandi; Prinetto, Paolo; Trotta, Pascal

    2015-09-01

    Cobham Gaisler develops the LEON3FT SPARC V8 fault-tolerant microprocessor that is available both as IP cores part of an IP library (GRLIB) that allows users to design their own custom system-on-chip (SoC) designs, and also as part of ready-made designs and devices. Cobham Gaisler has recently added support for Microsemi IGLOO2, and experimental support for Microsemi radiation-tolerant RTG4, devices to GRLIB.

  9. Towards 4th generation biomaterials: a covalent hybrid polymer-ormoglass architecture

    NASA Astrophysics Data System (ADS)

    Sachot, N.; Mateos-Timoneda, M. A.; Planell, J. A.; Velders, A. H.; Lewandowska, M.; Engel, E.; Castaño, O.

    2015-09-01

    Hybrid materials are being extensively investigated with the aim of mimicking the ECM microenvironment to develop effective solutions for bone tissue engineering. However, the common drawbacks of a hybrid material are the lack of interactions between the scaffold's constituents and the masking of its bioactive phase. Conventional hybrids often degrade in a non-homogeneous manner and the biological response is far from optimal. We have developed a novel material with strong interactions between constituents. The bioactive phase is directly exposed on its surface mimicking the structure of the ECM of bone. Here, polylactic acid electrospun fibers have been successfully and reproducibly coated with a bioactive organically modified glass (ormoglass, Si-Ca-P2 system) covalently. In comparison with the pure polymeric mats, the fibers obtained showed improved hydrophilicity and mechanical properties, bioactive ion release, exhibited a nanoroughness and enabled good cell adhesion and spreading after just one day of culture (rMSCs and rEPCs). The fibers were coated with different ormoglass compositions to tailor their surface properties (roughness, stiffness, and morphology) by modifying the experimental parameters. Knowing that cells modulate their behavior according to the exposed physical and chemical signals, the development of this instructive material is a valuable advance in the design of functional regenerative biomaterials.Hybrid materials are being extensively investigated with the aim of mimicking the ECM microenvironment to develop effective solutions for bone tissue engineering. However, the common drawbacks of a hybrid material are the lack of interactions between the scaffold's constituents and the masking of its bioactive phase. Conventional hybrids often degrade in a non-homogeneous manner and the biological response is far from optimal. We have developed a novel material with strong interactions between constituents. The bioactive phase is directly exposed on its surface mimicking the structure of the ECM of bone. Here, polylactic acid electrospun fibers have been successfully and reproducibly coated with a bioactive organically modified glass (ormoglass, Si-Ca-P2 system) covalently. In comparison with the pure polymeric mats, the fibers obtained showed improved hydrophilicity and mechanical properties, bioactive ion release, exhibited a nanoroughness and enabled good cell adhesion and spreading after just one day of culture (rMSCs and rEPCs). The fibers were coated with different ormoglass compositions to tailor their surface properties (roughness, stiffness, and morphology) by modifying the experimental parameters. Knowing that cells modulate their behavior according to the exposed physical and chemical signals, the development of this instructive material is a valuable advance in the design of functional regenerative biomaterials. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04275e

  10. Injector Beam Dynamics for a High-Repetition Rate 4th-Generation Light Source

    SciTech Connect

    Papadopoulos, C. F.; Corlett, J.; Emma, P.; Filippetto, D.; Penn, G.; Qiang, J.; Reinsch, M.; Sannibale, F.; Steier, C.; Venturini, M.; Wells, R.

    2013-05-20

    We report on the beam dynamics studies and optimization methods for a high repetition rate (1 MHz) photoinjector based on a VHF normal conducting electron source. The simultaneous goals of beamcompression and reservation of 6-dimensional beam brightness have to be achieved in the injector, in order to accommodate a linac driven FEL light source. For this, a parallel, multiobjective optimization algorithm is used. We discuss the relative merits of different injector design points, as well as the constraints imposed on the beam dynamics by technical considerations such as the high repetition rate.

  11. Towards 4th generation biomaterials: a covalent hybrid polymer-ormoglass architecture.

    PubMed

    Sachot, N; Mateos-Timoneda, M A; Planell, J A; Velders, A H; Lewandowska, M; Engel, E; Castaño, O

    2015-10-01

    Hybrid materials are being extensively investigated with the aim of mimicking the ECM microenvironment to develop effective solutions for bone tissue engineering. However, the common drawbacks of a hybrid material are the lack of interactions between the scaffold's constituents and the masking of its bioactive phase. Conventional hybrids often degrade in a non-homogeneous manner and the biological response is far from optimal. We have developed a novel material with strong interactions between constituents. The bioactive phase is directly exposed on its surface mimicking the structure of the ECM of bone. Here, polylactic acid electrospun fibers have been successfully and reproducibly coated with a bioactive organically modified glass (ormoglass, Si-Ca-P2 system) covalently. In comparison with the pure polymeric mats, the fibers obtained showed improved hydrophilicity and mechanical properties, bioactive ion release, exhibited a nanoroughness and enabled good cell adhesion and spreading after just one day of culture (rMSCs and rEPCs). The fibers were coated with different ormoglass compositions to tailor their surface properties (roughness, stiffness, and morphology) by modifying the experimental parameters. Knowing that cells modulate their behavior according to the exposed physical and chemical signals, the development of this instructive material is a valuable advance in the design of functional regenerative biomaterials. PMID:26332471

  12. FIB–SEM tomography of 4th generation PWA 1497 superalloy

    SciTech Connect

    Ziętara, Maciej Kruk, Adam Gruszczyński, Adam Czyrska-Filemonowicz, Aleksandra

    2014-01-15

    The effect of creep deformation on the microstructure of the PWA 1497 single crystal Ni-base superalloy developed for turbine blade applications was investigated. The aim of the present study was to characterize quantitatively a superalloy microstructure and subsequent development of rafted γ′ precipitates in the PWA 1497 during creep deformation at 982 °C and 248 MPa up to rupture. The PWA1497 microstructure was characterized by scanning electron microscopy and FIB–SEM electron tomography. The 3D reconstruction of the PWA1497 microstructure is presented and discussed. - Highlights: • The microstructure of PWA1497 superalloy was examined using FIB–SEM tomography. • In case of modern single crystal superalloys, measurements of A{sub A} are adequate for V{sub V}. • During creep the γ channel width increases from 65 to 193 nm for ruptured specimen. • Tomography is a useful technique for quantitative studies of material microstructure.

  13. 33 CFR 165.166 - Safety Zone: Macy's July 4th Fireworks, East River, NY.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... CFR 165.23 apply. (2) No vessels, except the Staten Island Ferries, will be allowed to transit the... Fireworks, East River, NY. 165.166 Section 165.166 Navigation and Navigable Waters COAST GUARD, DEPARTMENT... § 165.166 Safety Zone: Macy's July 4th Fireworks, East River, NY. (a) Regulated area. The following...

  14. 33 CFR 165.166 - Safety Zone: Macy's July 4th Fireworks, East River, NY.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... CFR 165.23 apply. (2) No vessels, except the Staten Island Ferries, will be allowed to transit the... Fireworks, East River, NY. 165.166 Section 165.166 Navigation and Navigable Waters COAST GUARD, DEPARTMENT... § 165.166 Safety Zone: Macy's July 4th Fireworks, East River, NY. (a) Regulated area. The following...

  15. 33 CFR 165.166 - Safety Zone: Macy's July 4th Fireworks, East River, NY.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... CFR 165.23 apply. (2) No vessels, except the Staten Island Ferries, will be allowed to transit the... Fireworks, East River, NY. 165.166 Section 165.166 Navigation and Navigable Waters COAST GUARD, DEPARTMENT... § 165.166 Safety Zone: Macy's July 4th Fireworks, East River, NY. (a) Regulated area. The following...

  16. 33 CFR 165.166 - Safety Zone: Macy's July 4th Fireworks, East River, NY.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... CFR 165.23 apply. (2) No vessels, except the Staten Island Ferries, will be allowed to transit the... Fireworks, East River, NY. 165.166 Section 165.166 Navigation and Navigable Waters COAST GUARD, DEPARTMENT... § 165.166 Safety Zone: Macy's July 4th Fireworks, East River, NY. (a) Regulated area. The following...

  17. 33 CFR 165.166 - Safety Zone: Macy's July 4th Fireworks, East River, NY.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... CFR 165.23 apply. (2) No vessels, except the Staten Island Ferries, will be allowed to transit the... Fireworks, East River, NY. 165.166 Section 165.166 Navigation and Navigable Waters COAST GUARD, DEPARTMENT... § 165.166 Safety Zone: Macy's July 4th Fireworks, East River, NY. (a) Regulated area. The following...

  18. 75 FR 34639 - Safety Zone; Reedville July 4th Celebration, Cockrell's Creek, Reedville, VA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-18

    ... the Reedville July 4th Celebration event. This action is intended to restrict vessel traffic movement... Celebration, Cockrell's Creek, Reedville, VA in the Federal Register (75 FR 26157). We received no comments on... standards bodies. This rule does not use technical standards. Therefore, we did not consider the use...

  19. 4th level of 1913 elevator indicating sacking scale, part of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4th level of 1913 elevator indicating sacking scale, part of the bagging system and nate to the sewing machine. Discharge spout for the grain bin to the left - Stewart Company Grain Elevator, 16 West Carson Street, Pittsburgh, Allegheny County, PA

  20. 4th level of 1945 warehouse indicating drag conveyor. From here ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4th level of 1945 warehouse indicating drag conveyor. From here screenings were pumped from the elevator leg to this conveyor. The grains were ground, then conveyed back down to the first floor for bagging. - Stewart Company Grain Elevator, 16 West Carson Street, Pittsburgh, Allegheny County, PA

  1. Improving the Attitudes of 4th Graders toward Older People through a Multidimensional Intergenerational Program

    ERIC Educational Resources Information Center

    Lynott, Patricia P.; Merola, Pamela R.

    2007-01-01

    The purpose of this study was to examine the effects of an intergenerational program on children's attitudes toward older people. Four 4th grade classes, one each during the years 2002 through 2005, participated in the study. The elders and school children engaged in meaningful activities over a 5 month period, including the performance of a play…

  2. Reading Development and Achievement of 4th-Grade Hmong Students

    ERIC Educational Resources Information Center

    Mahowald, Megan; Loughnane, Megan

    2016-01-01

    Researchers and practitioners alike have noted that Hmong students in the United States do not achieve as well as their monolingual peers and other bilingual students. The current mixed-methods study is designed to describe reading development and achievement of 4th-grade Hmong students in one large, urban school district. This study explores the…

  3. 15. Old Bergen tunnel, west end, showing proposed 4th track ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    15. Old Bergen tunnel, west end, showing proposed 4th track of Delaware, Lackawanna and Western Railroad and amount of west end of tunnel to be taken out to allow for same, taken August 13, 1906 - Erie Railway, Bergen Hill Open Cut, Palisade Avenue to Tonnele Avenue, Jersey City, Hudson County, NJ

  4. 11. 4TH FLOOR, HOTEL SOAP LINE No. 6 TO NORTHEAST, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    11. 4TH FLOOR, HOTEL SOAP LINE No. 6 TO NORTHEAST, WITH WRAPPER (LEFT), PRESS (CENTER), AND CUTTER (RIGHT, BEHIND CHUTE); BUCKET CONVEYOR AT RIGHT MOVED WASTE FROM PRESS TO 5TH FLOOR FOR RE-MANUFACTURE - Colgate & Company Jersey City Plant, Building No. B-14, 54-58 Grand Street, Jersey City, Hudson County, NJ

  5. 77 FR 56208 - Filing Dates for the Kentucky Special Election in the 4th Congressional District

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-12

    ... From the Federal Register Online via the Government Publishing Office FEDERAL ELECTION COMMISSION Filing Dates for the Kentucky Special Election in the 4th Congressional District AGENCY: Federal Election Commission. ACTION: Notice of filing dates for special election. SUMMARY: Kentucky has scheduled a...

  6. 77 FR 39408 - Safety Zone; Buffalo July 4th Fireworks, Lake Erie, Buffalo, NY

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-03

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Buffalo July 4th Fireworks, Lake Erie, Buffalo, NY AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast Guard is establishing a temporary safety zone on Lake Erie, Buffalo, NY. This safety zone is intended to...

  7. Improving Social Interaction among 4th Grade Students through Social Skills Instruction.

    ERIC Educational Resources Information Center

    Dunleavy, Shannon; Karwowski, Sandra; Shudes-Eitel, Jennifer

    This action research project implemented a program for improving social skills in order to establish positive interaction among 4th grade students at a northern Chicago suburban school. Social skills deficiency was documented through behavior checklists and referrals, teacher observations and student reflection. Teachers reported that low incomes,…

  8. 20. TYPICAL VIEW OF FRONT WINDOWS FROM 4TH TO 9TH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. TYPICAL VIEW OF FRONT WINDOWS FROM 4TH TO 9TH FLOOR WITH WHITE GLAZED TERRA COTTA SILL AND HEADERS. MULLIONS ARE ORANGE BROWN BRICKS LIKE THE WALLS. BRICKS ARE IN FLEMISH BOND PATTERN. - Pacific Telephone & Telegraph Company Building, 1519 Franklin Street, Oakland, Alameda County, CA

  9. MAIN GATE, INTERSECTION OF 4TH AVE (200 NORTH) AND N ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MAIN GATE, INTERSECTION OF 4TH AVE (200 NORTH) AND N STREET (895 EAST), SALT LAKE CITY, UT. VIEW LOOKING EAST THROUGH MAIN CEMETERY GATE TO CEMETERY'S MAIN STREET, REPHOTOGRAPH OF HISTORIC SHIPLER PHOTO # 18276, UTAH STATE HISTORICAL SOCIETY COLLECTION. - Salt Lake City Cemetery, 200 N Street, Salt Lake City, Salt Lake County, UT

  10. Assessment of an Engineering Technology Outreach Program for 4th-7th Grade Girls

    ERIC Educational Resources Information Center

    Dell, Elizabeth M.; Christman, Jeanne; Garrick, Robert D.

    2011-01-01

    This paper describes a workshop led by female Engineering Technology students, with support from female faculty, to provide an introduction to Engineering Technology to 4th-7th grade girls through a series of interactive laboratory experiments. This outreach program was developed to improve attitudes towards science and engineering in middle…

  11. [Prescribing practices of fluoroquinolones in Tunisia].

    PubMed

    Hachfi, W; Kaabia, N; Bougmiza, I; Bellazreg, F; Hattab, Z; Ben Lasfar, N; Bahri, F; Letaief, A

    2011-04-01

    The aim of the study was to assess the prescribing practices of fluoroquinolones (FQ) among general practionners in the town of Sousse (central-eastern Tunisia). A transversal study was made between the first and the 23rd April, 2009, among general practionners working in Sousse. For each prescription, informations about patients, indications and modalities of treatment were collected on a questionnaire. These prescriptions were compared to Tunisian and/or French guidelines for antibiotics use. One hundred and eighty eight FQ prescriptions were analyzed. The mean age of patients was 50 years. FQ were more often used alone (83%) and in first line intention (84%). The molecules used were essentially ciprofloxacin (44.7%), levofloxacin (35.6%) and ofloxacin (18.6%). The indications were mainly bronchopulmonary infections (34%) and urinary tract infection (32%). These choices were in accordance with guidelines in 41% of the prescriptions. The dosage was adapted, but the duration of treatment was often excessive. Further efforts are needed, to optimize the good use of FQ in order to reduce or stabilize the rate of bacterial resistance.

  12. Fluoroquinolone antibiotics: an emerging class of environmental micropollutants.

    PubMed

    Van Doorslaer, Xander; Dewulf, Jo; Van Langenhove, Herman; Demeestere, Kristof

    2014-12-01

    The aim of this review paper is to provide a comprehensive overview of different chemical and environmental aspects concerning fluoroquinolone antibiotics as emerging contaminants. A literature survey has been performed based on 204 papers from 1998 to mid-2013, resulting in a dataset consisting out of 4100 data points related to physical-chemical properties, environmental occurrence, removal efficiencies, and ecotoxicological data. In a first part, an overview is given on relevant physical-chemical parameters to better understand the behavior of fluoroquinolones during wastewater treatment and in the environment. Secondly, the route of these antibiotics after their application in both human and veterinary surroundings is discussed. Thirdly, the occurrence of fluoroquinolone residues is discussed for different environmental matrices. The final part of this review provides a tentative risk assessment of fluoroquinolone compounds and their transformation products in surface waters by means of hazard quotients. Overall, this review shows that fluoroquinolone antibiotics have a wide spread use and that their behavior during wastewater treatment is complex with an incomplete removal. As a result, it is observed that these biorecalcitrant compounds are present in different environmental matrices at potentially hazardous concentrations for the aquatic environment. The latter calls for actions on both the consumption as well as the wastewater treatment aspect to diminish the discharge of these biological active compounds. PMID:25226071

  13. Fluoroquinolone antibiotics: an emerging class of environmental micropollutants.

    PubMed

    Van Doorslaer, Xander; Dewulf, Jo; Van Langenhove, Herman; Demeestere, Kristof

    2014-12-01

    The aim of this review paper is to provide a comprehensive overview of different chemical and environmental aspects concerning fluoroquinolone antibiotics as emerging contaminants. A literature survey has been performed based on 204 papers from 1998 to mid-2013, resulting in a dataset consisting out of 4100 data points related to physical-chemical properties, environmental occurrence, removal efficiencies, and ecotoxicological data. In a first part, an overview is given on relevant physical-chemical parameters to better understand the behavior of fluoroquinolones during wastewater treatment and in the environment. Secondly, the route of these antibiotics after their application in both human and veterinary surroundings is discussed. Thirdly, the occurrence of fluoroquinolone residues is discussed for different environmental matrices. The final part of this review provides a tentative risk assessment of fluoroquinolone compounds and their transformation products in surface waters by means of hazard quotients. Overall, this review shows that fluoroquinolone antibiotics have a wide spread use and that their behavior during wastewater treatment is complex with an incomplete removal. As a result, it is observed that these biorecalcitrant compounds are present in different environmental matrices at potentially hazardous concentrations for the aquatic environment. The latter calls for actions on both the consumption as well as the wastewater treatment aspect to diminish the discharge of these biological active compounds.

  14. Spectrofluorimetric determination of fluoroquinolones in pharmaceutical preparations.

    PubMed

    Ulu, Sevgi Tatar

    2009-02-01

    Simple, rapid and highly sensitive spectrofluorimetric method is presented for the determination of four fluoroquinolone (FQ) drugs, ciprofloxacin, enoxacin, norfloxacin and moxifloxacin in pharmaceutical preparations. Proposed method is based on the derivatization of FQ with 4-chloro-7-nitrobenzofurazan (NBD-Cl) in borate buffer of pH 9.0 to yield a yellow product. The optimum experimental conditions have been studied carefully. Beer's law is obeyed over the concentration range of 23.5-500 ng mL(-1) for ciprofloxacin, 28.5-700 ng mL(-1) for enoxacin, 29.5-800 ng mL(-1) for norfloxacin and 33.5-1000 ng mL(-1) for moxifloxacin using NBD-Cl reagent, respectively. The detection limits were found to be 7.0 ng mL(-1) for ciprofloxacin, 8.5 ng mL(-1) for enoxacin, 9.2 ng mL(-1) for norfloxacin and 9.98 ng mL(-1) for moxifloxacin, respectively. Intra-day and inter-day relative standard deviation and relative mean error values at three different concentrations were determined. The low relative standard deviation values indicate good precision and high recovery values indicate accuracy of the proposed methods. The method is highly sensitive and specific. The results obtained are in good agreement with those obtained by the official and reference method. The results presented in this report show that the applied spectrofluorimetric method is acceptable for the determination of the four FQ in the pharmaceutical preparations. Common excipients used as additives in pharmaceutical preparations do not interfere with the proposed method.

  15. Critical study of observation of the sternal end of the right 4th rib.

    PubMed

    Fanton, Laurent; Gustin, Marie-Paule; Paultre, Ulysse; Schrag, Bettina; Malicier, Daniel

    2010-03-01

    Studies of the method of estimating age at death by the 4th rib exclusively concerned the phase method without fundamentally challenging the method as such. The present study analyzed observation of the variables on which the Işcan method is based. Ten observers made two assessments of the stage of pit depth, pit shape, rim and wall configurations of 59 right 4th ribs harvested from males (mean age: 49 years; range: 47-94 years). Observation showed poor reproducibility and repeatability for all three variables (Wilcoxon test, kappa-coefficient). Analysis of problem ribs revealed difficulty in measuring and imprecision in describing pit depth and failure to take account of continual aging for the other two variables. Despite these results, Işcan's variables provide objective information on age at death. It is recommended that the method be improved by better description of the variables and use of multivariate statistical analysis.

  16. Fluoroquinolone-resistant Streptococcus agalactiae isolates from Argentina.

    PubMed

    Faccone, D; Guerriero, L; Méndez, E; Errecalde, L; Cano, H; Yoyas, N; Togneri, A; Romanowski, V; Galas, M; Whonet, Red; Corso, A

    2010-01-01

    Fluoroquinolone resistance is a growing problem that has only recently emerged in S. agalactiae. Between 2005-2007, WHONET--Argentina network evaluated levofloxacin susceptibility in 1128 clinical S. agalactiae isolates, 10 (0.9%) of which proved to be resistant. Nine of them had come from 5 hospitals (in Buenos Aires City and 4 Argentinean provinces) and recovered from urine (n=7) and vaginal screening cultures (n=2). Three strains were also resistant to macrolides, lincosamides and B streptogramins due to the ermA gene. All nine fluoroquinolone-resistant isolates bore the same two mutations, Ser79Phe in ParC and Ser81Leu in GyrA proteins. Genetic relationships were analyzed by Apal-PFGE and two clones were determined, A (n=6) and B (n=3). To our knowledge, these are the first fluoroquinolone-resistant S. agalactiae isolates detected in Latin America.

  17. Recombinagenic and mutagenic activities of fluoroquinolones in Drosophila melanogaster.

    PubMed

    Thomé, Simone; Bizarro, Cassiane Rosa; Lehmann, Mauricio; de Abreu, Bianca Regina Ribas; de Andrade, Heloisa Helena Rodrigues; Cunha, Kênya Silva; Dihl, Rafael Rodrigues

    2012-02-18

    Fluoroquinolones are widely used in human and in veterinary medicine due to their broad-spectrum antibacterial activity. They act by inhibiting type II DNA topoisomerases (gyrase and topoisomerase IV). Because of the sequence homology between prokaryotic and eukaryotic topoisomerases II, fluoroquinolones can pose a hazard to eukaryotic cells. However, published information concerning the genotoxic profiles of these drugs in vivo is sparse and inconsistent. We have assessed the activities of three fluoroquinolones, ciprofloxacin, enrofloxacin and norfloxacin, in the Drosophila melanogaster Somatic Mutation and Recombination Test (SMART) and measured their mutagenic and recombinagenic potentials. Norfloxacin was non-genotoxic. Ciprofloxacin and enrofloxacin induced significant increases in spot frequencies in trans-heterozygous flies. To test the roles of somatic recombination and mutation in the observed genotoxicity, balancer-heterozygous flies were also analyzed. Ciprofloxacin and enrofloxacin were preferential inducers of homologous recombination in proliferative cells, an event linked to loss of heterozygosity. PMID:22142834

  18. Spontaneous bilateral patellar tendon rupture: case report and review of fluoroquinolone-induced tendinopathy.

    PubMed

    Rosa, Bárbara; Campos, Pedro; Barros, André; Karmali, Samir; Gonçalves, Ricardo

    2016-07-01

    The present case emphasizes the importance of adhering to strict indications when prescribing fluoroquinolones. Although rare, drug-induced tendinopathy is not confined to fluoroquinolones. The patient's and physician's awareness should be increased to reduce fluoroquinolones-associated morbidity, particularly in patients with previously described risk factors. PMID:27386128

  19. 11(th) National Meeting of Organic Chemistry and 4(th) Meeting of Therapeutic Chemistry.

    PubMed

    Sousa, Maria Emília; Araújo, Maria João; do Vale, Maria Luísa; Andrade, Paula B; Branco, Paula; Gomes, Paula; Moreira, Rui; Pinho E Melo, Teresa M V D; Freitas, Victor

    2016-03-17

    For the first time under the auspices of Sociedade Portuguesa de Química, the competences of two important fields of Chemistry are brought together into a single event, the 11st National Organic Chemistry Meeting and the the 4th National Medicinal Chemistry Meeting, to highlight complementarities and to promote new synergies. Abstracts of plenary lectures, oral communications, and posters presented during the meeting are collected in this report.

  20. 10. 4TH FLOOR, HOTEL SOAP LINE No. 6 TO SOUTHWEST, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. 4TH FLOOR, HOTEL SOAP LINE No. 6 TO SOUTHWEST, WITH AUTOMATIC CUTTER (LEFT), PRESS (CENTER), AND WRAPPER (RIGHT); LARGE CHUTE AT CENTER FROM 5TH FLOOR BINS TO 3RD FLOOR SOAP MILLS; OVERHEAD AND FLOOR (LOWER RIGHT) FINISHED GOODS CONVEYORS TO G BLOCK (HAER NO. NJ-71-NN) - Colgate & Company Jersey City Plant, Building No. B-14, 54-58 Grand Street, Jersey City, Hudson County, NJ

  1. 11(th) National Meeting of Organic Chemistry and 4(th) Meeting of Therapeutic Chemistry.

    PubMed

    Sousa, Maria Emília; Araújo, Maria João; do Vale, Maria Luísa; Andrade, Paula B; Branco, Paula; Gomes, Paula; Moreira, Rui; Pinho E Melo, Teresa M V D; Freitas, Victor

    2016-01-01

    For the first time under the auspices of Sociedade Portuguesa de Química, the competences of two important fields of Chemistry are brought together into a single event, the 11st National Organic Chemistry Meeting and the the 4th National Medicinal Chemistry Meeting, to highlight complementarities and to promote new synergies. Abstracts of plenary lectures, oral communications, and posters presented during the meeting are collected in this report. PMID:27102166

  2. 11th National Meeting of Organic Chemistry and 4th Meeting of Therapeutic Chemistry

    PubMed Central

    Sousa, Maria Emília; Araújo, Maria João; do Vale, Maria Luísa; Andrade, Paula B.; Branco, Paula; Gomes, Paula; Moreira, Rui; Pinho e Melo, Teresa M.V.D.; Freitas, Victor

    2016-01-01

    For the first time under the auspices of Sociedade Portuguesa de Química, the competences of two important fields of Chemistry are brought together into a single event, the 11st National Organic Chemistry Meeting and the the 4th National Medicinal Chemistry Meeting, to highlight complementarities and to promote new synergies. Abstracts of plenary lectures, oral communications, and posters presented during the meeting are collected in this report. PMID:27102166

  3. [Use of molecular-biological microchip TB-BIOCHIP-2 for detecting of Mycobacterium tuberculosis with multidrug resistance to fluoroquinolones in patients with new detected and chronic tuberculosis].

    PubMed

    Nosova, E Iu; Galkina, K Iu; Antonova, O V; Garmash, Iu Iu; Skotnikova, O I; Moroz, A M

    2008-01-01

    At present the left-handed "respiratory" quinolones such as moxifloxacin and levofloxacin are the most promising drugs for therapy of multidrug resistant tuberculosis (MDR). Fast and specific diagnostics of sensitivity of M. tuberculosis (MBT) with MDR to this group of drugs is required for timely prescription of adequate chemotherapy and its correction in case of MBT resistance to fluoroquinolones. A new generation of biological microchips - TB-BIOCHIP-2 makes possible to detect 9 mutation types in quinolones resistant determination region (QRDR) of gene. About 800 samples from 169 patients in Antituberculosis center were studied. In patients with new detected tuberculosis 23.5% MBT resistant to isoniazid and rifampicin (MDR) and sensitive to fluoroquinolones were revealed. In patients with chronic tuberculosis 65.5% MBT-MDR were revealed. Our results were confirmed with detecting ofloxacin resistance on Lowenstein - Jensen. In addition efficiency of TB-BIOCHIP-2 to control drug testing sensitivity of MBT-MDR on fluoroquinolones was confirmed.

  4. A prospective controlled trial of teaching basic surgical skills with 4th year medical students.

    PubMed

    Lossing, A; Groetzsch, G

    1992-01-01

    Scrubbing, gowning, gloving and aseptic technique are currently the only formal teaching 4th year medical students receive at the beginning of an 8-week surgery rotation. Teaching is often delegated to junior house staff and early bad habits are difficult to unlearn in post-graduate training. A study population of 4th year medical students from three hospitals were examined. At the beginning of an 8-week surgery rotation technical skills were tested with a simulation appendectomy model at the beginning and end of the surgery rotation. On day one, after a pre-test, a teaching intervention was alternated between two hospitals. A control group received only a post-test. The outcome measure was a cumulative score of the students' performance in technical stations in the simulation model. A comparison was made of the mean post-test scores in the teaching, non-teaching and control groups. An analysis of variance of all post-test scores rejected the null hypothesis at the 0.05 level. Duncan's multiple range test demonstrated a significant difference between the teaching and non-teaching group. Feedback from 25 students indicated the teaching model was practical and relevant. A formal teaching intervention of basic technical skills with 4th year medical students improved their performance on a simulated appendectomy model.

  5. Control of fluoroquinolone resistance through successful regulation, Australia.

    PubMed

    Cheng, Allen C; Turnidge, John; Collignon, Peter; Looke, David; Barton, Mary; Gottlieb, Thomas

    2012-09-01

    Fluoroquinolone antimicrobial drugs are highly bioavailable, broad-spectrum agents with activity against gram-negative pathogens, especially those resistant to other classes of antimicrobial drugs. Australia has restricted the use of quinolones in humans through its national pharmaceutical subsidy scheme; and, through regulation, has not permitted the use of quinolones in food-producing animals. As a consequence, resistance to fluoroquinolones in the community has been slow to emerge and has remained at low levels in key pathogens, such as Escherichia coli. In contrast to policies in most other countries, this policy has successfully preserved the utility of this class of antimicrobial drugs for treatment of most infections. PMID:22932272

  6. SOS response and its regulation on the fluoroquinolone resistance

    PubMed Central

    Qin, Ting-Ting; Kang, Hai-Quan; Ma, Ping; Li, Peng-Peng; Huang, Lin-Yan

    2015-01-01

    Bacteria can survive fluoroquinolone antibiotics (FQs) treatment by becoming resistant through a genetic change—mutation or gene acquisition. The SOS response is widespread among bacteria and exhibits considerable variation in its composition and regulation, which is repressed by LexA protein and derepressed by RecA protein. Here, we take a comprehensive review of the SOS gene network and its regulation on the fluoroquinolone resistance. As a unique survival mechanism, SOS may be an important factor influencing the outcome of antibiotic therapy in vivo. PMID:26807413

  7. SOS response and its regulation on the fluoroquinolone resistance.

    PubMed

    Qin, Ting-Ting; Kang, Hai-Quan; Ma, Ping; Li, Peng-Peng; Huang, Lin-Yan; Gu, Bing

    2015-12-01

    Bacteria can survive fluoroquinolone antibiotics (FQs) treatment by becoming resistant through a genetic change-mutation or gene acquisition. The SOS response is widespread among bacteria and exhibits considerable variation in its composition and regulation, which is repressed by LexA protein and derepressed by RecA protein. Here, we take a comprehensive review of the SOS gene network and its regulation on the fluoroquinolone resistance. As a unique survival mechanism, SOS may be an important factor influencing the outcome of antibiotic therapy in vivo.

  8. BET 2: Do fluoroquinolones increase the incidence of tendinopathy?

    PubMed

    Baombe, Janos P; Ford, Rebecca

    2016-07-01

    A shortcut review of the literature was carried out to establish whether the use of fluoroquinolones was associated with an increased risk of tendinopathy in adult patients. 10 trials were found to be directly relevant to the three-part question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is that there is an association between the use of fluoroquinolones and a broad range of tendinopathies. PMID:27330182

  9. Can astronomy enhance UNESCO World Heritage recognition? The paradigm of 4th Dynasty Egyptian pyramids

    NASA Astrophysics Data System (ADS)

    Belmonte, Juan Antonio

    2015-08-01

    The pyramids of Egypt, notably those of the 4th Dinasty as Giza, have always be considered an unmistikable part of human world heritage as the only surviving wonders of the Ancient World. Their majesty, technical hability and innovative character have always beeen considered as representative of ancient Egyptian ingenuity. However, past and present fringe theories about the pyramids and astronomy have always polluted the role of our discipline in the design, construction and symbolism of these impressive monuments. This is indeed unfear. Fortunately, things have started to change in the last couple of decades and now astronomy is interpreted as a neccessary tool for the correct interpretation of the astral eschatology present in the 5th and 6th Dynasty Texts of the Pyramids. Although the pyramid complexes of the 4th Dynasty are mute, there is however recent research showing that a strong astral symbolism could be hidden in many aspects of the complex architecture and in the design of these exceptional monuments. This idea comes from several hints obtained not only from planning and construction, but also from epigraphy and the analysis of celestial and local landscapes. Chronology also plays a most relevant role on this. The pyramid complexes of the 4th Dynasty at Meidum, Dahshur, Giza and Abu Rowash -- all of which enjoy UNESCO World Heritage recognition -- willl be scrutinized. As a consequence, we will show how astronomy can certainly enhance the face value of these extraordinary monuments as a definitive proof of the ancient Egyptian quest for Ma'at, i.e. their perennial obsesion for Cosmic Order.

  10. Proceedings of the 4th International Conference and Exhibition: World Congress on Superconductivity, Volume 2

    NASA Technical Reports Server (NTRS)

    Krishen, Kumar (Editor); Burnham, Calvin (Editor)

    1995-01-01

    This document contains papers presented at the 4th International Conference Exhibition: World Congress on Superconductivity held June 27-July 1, 1994 in Orlando, Florida. These documents encompass research, technology, applications, funding, political, and social aspects of superconductivity. The areas covered included: high-temperature materials; thin films; C-60 based superconductors; persistent magnetic fields and shielding; fabrication methodology; space applications; physical applications; performance characterization; device applications; weak link effects and flux motion; accelerator technology; superconductivity energy; storage; future research and development directions; medical applications; granular superconductors; wire fabrication technology; computer applications; technical and commercial challenges; and power and energy applications.

  11. Proceedings of the 4th International Conference and Exhibition: World Congress on Superconductivity, volume 1

    NASA Technical Reports Server (NTRS)

    Krishen, Kumar (Editor); Burnham, Calvin (Editor)

    1995-01-01

    The papers presented at the 4th International Conference Exhibition: World Congress on Superconductivity held at the Marriott Orlando World Center, Orlando, Florida, are contained in this document and encompass the research, technology, applications, funding, political, and social aspects of superconductivity. Specifically, the areas covered included: high-temperature materials; thin films; C-60 based superconductors; persistent magnetic fields and shielding; fabrication methodology; space applications; physical applications; performance characterization; device applications; weak link effects and flux motion; accelerator technology; superconductivity energy; storage; future research and development directions; medical applications; granular superconductors; wire fabrication technology; computer applications; technical and commercial challenges, and power and energy applications.

  12. [Global Health. Information for change. 4th report of the Italian Observatory on Global Health].

    PubMed

    2011-01-01

    Global Health. Information for change. 4th report of the Italian Observatory on Global Health. InformAzione (InformAction) is the title of the last OISG report (Italian observatory on Global Health), dedicated to information and education, the essential bases for a conscious action aimed at decreasing inequalities. Increasing the investments in information, education and interventions oriented to global health may broaden the number of aware and informed citizens, able to start a dialogue, to make pressures to increase the interventions in favor of those in need.

  13. Multi-Dimensional Asymptotically Stable 4th Order Accurate Schemes for the Diffusion Equation

    NASA Technical Reports Server (NTRS)

    Abarbanel, Saul; Ditkowski, Adi

    1996-01-01

    An algorithm is presented which solves the multi-dimensional diffusion equation on co mplex shapes to 4th-order accuracy and is asymptotically stable in time. This bounded-error result is achieved by constructing, on a rectangular grid, a differentiation matrix whose symmetric part is negative definite. The differentiation matrix accounts for the Dirichlet boundary condition by imposing penalty like terms. Numerical examples in 2-D show that the method is effective even where standard schemes, stable by traditional definitions fail.

  14. Proceedings of the 4th International Workshop on Tritium Effects in Plasma Facing Components

    SciTech Connect

    R. A. Causey

    1999-02-01

    The 4th International Workshop on Tritium Effects in Plasma Facing Components was held in Santa Fe, New Mexico on May 14-15, 1998. This workshop occurs every two years, and has previously been held in Livermore/California, Nagoya/Japan, and the JRC-Ispra Site in Italy. The purpose of the workshop is to gather researchers involved in the topic of tritium migration, retention, and recycling in materials used to line magnetic fusion reactor walls and provide a forum for presentation and discussions in this area. This document provides an overall summary of the workshop, the workshop agenda, a summary of the presentations, and a list of attendees.

  15. Spiritual Health Scale 2011: Defining and Measuring 4th Dimension of Health

    PubMed Central

    Dhar, Neera; Chaturvedi, SK; Nandan, Deoki

    2011-01-01

    In the midst of physical comforts provided by the unprecedented developments in all spheres of life, the humanity is at cross roads and looking at something beyond these means. Spirituality has now been identified globally as an important aspect for providing answers to many questions related to health and happiness. The World Health Organization is also keen at looking beyond physical, mental and social dimensions of the health, and the member countries are actively exploring the 4th Dimension of the health i.e. the spiritual health and its impact on the overall health and happiness of an individual. National Institute of Health and Family Welfare (NIHFW), realized this need and initiated a research study in this direction. In this study, an effort was made to define this 4th Dimension of health from a common worldly person's perspective and measure it. 3 Domains, 6 Constructs and 27 Determinants of spiritual health were identified through a scientific process. A statistically reliable and valid Spiritual Health Scale (SHS 2011) containing 114 items has been developed. Construct validity and test- retest reliability has been established for urban educated adult population. The scale is first of its kind in the world to measure the spiritual health of a common worldly person, which is devoid of religious and cultural bias. Its items have universal applicability. PMID:22279257

  16. Computational aspects of the nonlinear normal mode initialization of the GLAS 4th order GCM

    NASA Technical Reports Server (NTRS)

    Navon, I. M.; Bloom, S. C.; Takacs, L.

    1984-01-01

    Using the normal modes of the GLAS 4th Order Model, a Machenhauer nonlinear normal mode initialization (NLNMI) was carried out for the external vertical mode using the GLAS 4th Order shallow water equations model for an equivalent depth corresponding to that associated with the external vertical mode. A simple procedure was devised which was directed at identifying computational modes by following the rate of increase of BAL sub M, the partial (with respect to the zonal wavenumber m) sum of squares of the time change of the normal mode coefficients (for fixed vertical mode index) varying over the latitude index L of symmetric or antisymmetric gravity waves. A working algorithm is presented which speeds up the convergence of the iterative Machenhauer NLNMI. A 24 h integration using the NLNMI state was carried out using both Matsuno and leap-frog time-integration schemes; these runs were then compared to a 24 h integration starting from a non-initialized state. The maximal impact of the nonlinear normal mode initialization was found to occur 6-10 hours after the initial time.

  17. PREFACE: 4th International Conference on Mathematical Modeling in Physical Sciences (IC-MSquare2015)

    NASA Astrophysics Data System (ADS)

    Vlachos, Dimitrios; Vagenas, Elias C.

    2015-09-01

    The 4th International Conference on Mathematical Modeling in Physical Sciences (IC-MSQUARE) took place in Mykonos, Greece, from Friday 5th June to Monday 8th June 2015. The Conference was attended by more than 150 participants and hosted about 200 oral, poster, and virtual presentations. There were more than 600 pre-registered authors. The 4th IC-MSQUARE consisted of different and diverging workshops and thus covered various research fields where Mathematical Modeling is used, such as Theoretical/Mathematical Physics, Neutrino Physics, Non-Integrable Systems, Dynamical Systems, Computational Nanoscience, Biological Physics, Computational Biomechanics, Complex Networks, Stochastic Modeling, Fractional Statistics, DNA Dynamics, Macroeconomics etc. The scientific program was rather intense as after the Keynote and Invited Talks in the morning, three parallel oral and one poster session were running every day. However, according to all attendees, the program was excellent with a high quality of talks creating an innovative and productive scientific environment for all attendees. We would like to thank the Keynote Speaker and the Invited Speakers for their significant contribution to IC-MSQUARE. We also would like to thank the Members of the International Advisory and Scientific Committees as well as the Members of the Organizing Committee.

  18. [Giant cell tumor of the 4th metacarpal bone of the left hand. Apropos of a case].

    PubMed

    Kamel, E J; Pinto, J A; Potenza, L; Michelena, A; Perez Signini, F; Fuenmayor, A

    1983-01-01

    He is a 46 year old patient that consults on a tumor that deforms the back of his left hand. The X-ray examination shows a bone osteolytic tumor with complete dis appearance of the 4th metacarpal. Surgical removal of the tumor was practiced with immediate reconstruction of the 4th metacarpal by an oseo-iliac graft. Anatomopathological examination. It is an ovoid tumor 6.5 long and irregular surface.

  19. 1:1 Ground-track resonance in a uniformly rotating 4th degree and order gravitational field

    NASA Astrophysics Data System (ADS)

    Feng, Jinglang; Noomen, Ron; Hou, Xiyun; Visser, Pieter; Yuan, Jianping

    2016-09-01

    Using a gravitational field truncated at the 4th degree and order, the 1:1 ground-track resonance is studied. To address the main properties of this resonance, a 1-degree of freedom (1-DOF) system is firstly studied. Equilibrium points (EPs), stability and resonance width are obtained. Different from previous studies, the inclusion of non-spherical terms higher than degree and order 2 introduces new phenomena. For a further study about this resonance, a 2-DOF model which includes a main resonance term (the 1-DOF system) and a perturbing resonance term is studied. With the aid of Poincaré sections, the generation of chaos in the phase space is studied in detail by addressing the overlap process of these two resonances with arbitrary combinations of eccentricity (e) and inclination (i). Retrograde orbits, near circular orbits and near polar orbits are found to have better stability against the perturbation of the second resonance. The situations of complete chaos are estimated in the e-i plane. By applying the maximum Lyapunov Characteristic Exponent (LCE), chaos is characterized quantitatively and similar conclusions can be achieved. This study is applied to three asteroids 1996 HW1, Vesta and Betulia, but the conclusions are not restricted to them.

  20. Beyond the genomics blueprint: the 4th Human Variome Project Meeting, UNESCO, Paris, 2012.

    PubMed

    Kohonen-Corish, Maija R J; Smith, Timothy D; Robinson, Helen M

    2013-07-01

    The 4th Biennial Meeting of the Human Variome Project Consortium was held at the headquarters of the United Nations Educational, Scientific and Cultural Organization (UNESCO) in Paris, 11-15 June 2012. The Human Variome Project, a nongovernmental organization and an official partner of UNESCO, enables the routine collection, curation, interpretation, and sharing of information on all human genetic variation. This meeting was attended by more than 180 delegates from 39 countries and continued the theme of addressing issues of implementation in this unique project. The meeting was structured around the four main themes of the Human Variome Project strategic plan, "Project Roadmap 2012-2016": setting normative function, behaving ethically, sharing knowledge, and building capacity. During the meeting, the members held extensive discussions to formulate an action plan in the key areas of the Human Variome Project. The actions agreed on were promulgated at the Project's two Advisory Council and Scientific Advisory Committee postconference meetings.

  1. Breakthrough in cardiac arrest: reports from the 4th Paris International Conference.

    PubMed

    Kudenchuk, Peter J; Sandroni, Claudio; Drinhaus, Hendrik R; Böttiger, Bernd W; Cariou, Alain; Sunde, Kjetil; Dworschak, Martin; Taccone, Fabio Silvio; Deye, Nicolas; Friberg, Hans; Laureys, Steven; Ledoux, Didier; Oddo, Mauro; Legriel, Stéphane; Hantson, Philippe; Diehl, Jean-Luc; Laterre, Pierre-Francois

    2015-12-01

    Jean-Luc Diehl The French Intensive Care Society organized on 5th and 6th June 2014 its 4th "Paris International Conference in Intensive Care", whose principle is to bring together the best international experts on a hot topic in critical care medicine. The 2014 theme was "Breakthrough in cardiac arrest", with many high-quality updates on epidemiology, public health data, pre-hospital and in-ICU cares. The present review includes short summaries of the major presentations, classified into six main chapters: Epidemiology of CA Pre-hospital management Post-resuscitation management: targeted temperature management Post-resuscitation management: optimizing organ perfusion and metabolic parameters Neurological assessment of brain damages Public healthcare. PMID:26380990

  2. The 4th annual European League Against Rheumatism congress in Lisbon: a personal perspective

    PubMed Central

    Wollheim, Frank A

    2004-01-01

    The 4th annual European League Against Rheumatism congress, held in Lisbon, 18–21 June 2003, had a record turnout of more than 8600 delegates and the abstract submissions increased to 2600. A heat wave and a somewhat substandard venue hampered some of the activities, notably the poster sessions. The scientific program was comprehensive and of a high class, and it was organized in 10–12 parallel sessions. The European League Against Rheumatism standing committees are expanding their activities and stimulating European cooperation (e.g. by creating databases and guidelines, and by starting research programs). The standing committees presented several areas where European cooperative work is in progress. Advances in drug therapy were a prominent theme and were well presented. Commercialism remains a problem for this meeting as for other similar large meetings, where satellite symposia surround the scientific program of the congress and often duplicate this. PMID:14979931

  3. General Chemistry Collection for Students (CD-ROM), Abstract of Special Issue 16, 4th Edition

    NASA Astrophysics Data System (ADS)

    2000-07-01

    The General Chemistry Collection contains both new and previously published JCE Software programs that are intended for use by introductory-level chemistry students. These peer-reviewed programs for Macintosh and for Windows are available on a single CD-ROM for convenient distribution to and access by students, and the CD may be adopted for students to purchase as they would a textbook. General Chemistry Collection covers a broad range of topics providing students with interesting information, tutorials, and simulations that will be useful to them as they study chemistry for the first time. There are 22 programs included in the General Chemistry Collection 4th Edition. Their titles and the general chemistry topics they cover are listed in Table 1. Features in This Edition General Chemistry Collection, 4th edition includes:

    • Lessons for Introductory Chemistry and INQUAL-S, two new programs not previously published by JCE Software (abstracts appear below)
    • Writing Electron Dot Structures (1) and Viscosity Measurement: A Virtual Experiment for Windows (2), two programs published individually by JCE Software
    • Periodic Table Live! LE, a limited edition of Periodic Table Live!, 2nd Edition (3) (this replaces Chemistry Navigator (4) and Illustrated Periodic Table (5))
    • Many of the programs from previous editions (6)1
    Hardware and Software Requirements System requirements are given in Table 2. Some programs have additional requirements. See the individual program abstracts at JCE Online, or documentation included on the CD-ROM for more specific information. Licensing and Discounts for Adoptions The General Chemistry Collection is intended for use by individual students. Institutions and faculty members may adopt General Chemistry Collection 4th Edition as they would a textbook. We can arrange for CDs to be packaged with laboratory manuals or other course materials or to be sold for direct distribution to students through the campus

  4. European Code against Cancer 4th Edition: Medical exposures, including hormone therapy, and cancer.

    PubMed

    Friis, Søren; Kesminiene, Ausrele; Espina, Carolina; Auvinen, Anssi; Straif, Kurt; Schüz, Joachim

    2015-12-01

    The 4th edition of the European Code against Cancer recommends limiting - or avoiding when possible - the use of hormone replacement therapy (HRT) because of the increased risk of cancer, nevertheless acknowledging that prescription of HRT may be indicated under certain medical conditions. Current evidence shows that HRT, generally prescribed as menopausal hormone therapy, is associated with an increased risk of cancers of the breast, endometrium, and ovary, with the risk pattern depending on factors such as the type of therapy (oestrogen-only or combined oestrogen-progestogen), duration of treatment, and initiation according to the time of menopause. Carcinogenicity has also been established for anti-neoplastic agents used in cancer therapy, immunosuppressants, oestrogen-progestogen contraceptives, and tamoxifen. Medical use of ionising radiation, an established carcinogen, can provide major health benefits; however, prudent practices need to be in place, with procedures and techniques providing the needed diagnostic information or therapeutic gain with the lowest possible radiation exposure. For pharmaceutical drugs and medical radiation exposure with convincing evidence on their carcinogenicity, health benefits have to be balanced against the risks; potential increases in long-term cancer risk should be considered in the context of the often substantial and immediate health benefits from diagnosis and/or treatment. Thus, apart from HRT, no general recommendations on reducing cancer risk were given for carcinogenic drugs and medical radiation in the 4th edition of European Code against Cancer. It is crucial that the application of these measures relies on medical expertise and thorough benefit-risk evaluation. This also pertains to cancer-preventive drugs, and self-medication with aspirin or other potential chemopreventive drugs is strongly discouraged because of the possibility of serious, potentially lethal, adverse events.

  5. Report of the 4th World Climate Research Programme International Conference on Reanalyses

    NASA Technical Reports Server (NTRS)

    Bosilovich, Michael G.; Rixen, Michel; van Oevelen, Peter; Asrar, Ghassem; Compo, Gilbert; Onogi, Kazutoshi; Simmons, Adrian; Trenberth, Kevin; Behringer, Dave; Bhuiyan, Tanvir Hossain; Capps, Shannon; Chaudhuri, Ayan; Chen, Junye; Chen, Linling; Colasacco-Thumm, Nicole; Escobar, Maria Gabriela; Ferguson, Craig R.; Ishibashi, Toshiyuki; Liberato, Margarida L. R.; Meng, Jesse; Molod, Andrea; Poli, Paul; Roundy, Joshua; Willett, Kate; Wollen, Jack

    2012-01-01

    The 4th WCRP International Conference on Reanalyses provided an opportunity for the international community to review and discuss the observational and modelling research, as well as process studies and uncertainties associated with reanalysis of the Earth System and its components. Characterizing the uncertainty and quality of reanalyses is a task that reaches far beyond the international community of producers, and into the interdisciplinary research community, especially those using reanalysis products in their research and applications. Reanalyses have progressed greatly even in the last 5 years, and newer ideas, projects and data are coming forward. While reanalysis has typically been carried out for the individual domains of atmosphere, ocean and land, it is now moving towards coupling using Earth system models. Observations are being reprocessed and they are providing improved quality for use in reanalysis. New applications are being investigated, and the need for climate reanalyses is as strong as ever. At the heart of it all, new investigators are exploring the possibilities for reanalysis, and developing new ideas in research and applications. Given the many centres creating reanalyses products (e.g. ocean, land and cryosphere research centres as well as NWP and atmospheric centers), and the development of new ideas (e.g. families of reanalyses), the total number of reanalyses is increasing greatly, with new and innovative diagnostics and output data. The need for reanalysis data is growing steadily, and likewise, the need for open discussion and comment on the data. The 4th Conference was convened to provide a forum for constructive discussion on the objectives, strengths and weaknesses of reanalyses, indicating potential development paths for the future.

  6. Food-based Science Curriculum Increases 4(th) Graders Multidisciplinary Science Knowledge.

    PubMed

    Hovland, Jana A; Carraway-Stage, Virginia G; Cela, Artenida; Collins, Caitlin; Díaz, Sebastián R; Collins, Angelo; Duffrin, Melani W

    2013-10-01

    Health professionals and policymakers are asking educators to place more emphasis on food and nutrition education. Integrating these topics into science curricula using hand-on, food-based activities may strengthen students' understanding of science concepts. The Food, Math, and Science Teaching Enhancement Resource (FoodMASTER) Initiative is a compilation of programs aimed at using food as a tool to teach mathematics and science. Previous studies have shown that students experiencing the FoodMASTER curriculum were very excited about the activities, became increasingly interested in the subject matter of food, and were able to conduct scientific observations. The purpose of this study was to: 1) assess 4(th) graders food-related multidisciplinary science knowledge, and 2) compare gains in food-related science knowledge after implementation of an integrated, food-based curriculum. During the 2009-2010 school year, FoodMASTER researchers implemented a hands-on, food-based intermediate curriculum in eighteen 4(th) grade classrooms in Ohio (n=9) and North Carolina (n=9). Sixteen classrooms in Ohio (n=8) and North Carolina (n=8), following their standard science curricula, served as comparison classrooms. Students completed a researcher-developed science knowledge exam, consisting of 13 multiple-choice questions administered pre- and post-test. Only subjects with pre- and post-test scores were entered into the sample (Intervention n=343; Control n=237). No significant differences were observed between groups at pre-test. At post-test, the intervention group scored (9.95±2.00) significantly higher (p=.000) than the control group (8.84±2.37) on a 13-point scale. These findings suggest the FoodMASTER intermediate curriculum is more effective than a standard science curriculum in increasing students' multidisciplinary science knowledge related to food. PMID:25152539

  7. Food-based Science Curriculum Increases 4(th) Graders Multidisciplinary Science Knowledge.

    PubMed

    Hovland, Jana A; Carraway-Stage, Virginia G; Cela, Artenida; Collins, Caitlin; Díaz, Sebastián R; Collins, Angelo; Duffrin, Melani W

    2013-10-01

    Health professionals and policymakers are asking educators to place more emphasis on food and nutrition education. Integrating these topics into science curricula using hand-on, food-based activities may strengthen students' understanding of science concepts. The Food, Math, and Science Teaching Enhancement Resource (FoodMASTER) Initiative is a compilation of programs aimed at using food as a tool to teach mathematics and science. Previous studies have shown that students experiencing the FoodMASTER curriculum were very excited about the activities, became increasingly interested in the subject matter of food, and were able to conduct scientific observations. The purpose of this study was to: 1) assess 4(th) graders food-related multidisciplinary science knowledge, and 2) compare gains in food-related science knowledge after implementation of an integrated, food-based curriculum. During the 2009-2010 school year, FoodMASTER researchers implemented a hands-on, food-based intermediate curriculum in eighteen 4(th) grade classrooms in Ohio (n=9) and North Carolina (n=9). Sixteen classrooms in Ohio (n=8) and North Carolina (n=8), following their standard science curricula, served as comparison classrooms. Students completed a researcher-developed science knowledge exam, consisting of 13 multiple-choice questions administered pre- and post-test. Only subjects with pre- and post-test scores were entered into the sample (Intervention n=343; Control n=237). No significant differences were observed between groups at pre-test. At post-test, the intervention group scored (9.95±2.00) significantly higher (p=.000) than the control group (8.84±2.37) on a 13-point scale. These findings suggest the FoodMASTER intermediate curriculum is more effective than a standard science curriculum in increasing students' multidisciplinary science knowledge related to food.

  8. European Code against Cancer 4th Edition: Medical exposures, including hormone therapy, and cancer.

    PubMed

    Friis, Søren; Kesminiene, Ausrele; Espina, Carolina; Auvinen, Anssi; Straif, Kurt; Schüz, Joachim

    2015-12-01

    The 4th edition of the European Code against Cancer recommends limiting - or avoiding when possible - the use of hormone replacement therapy (HRT) because of the increased risk of cancer, nevertheless acknowledging that prescription of HRT may be indicated under certain medical conditions. Current evidence shows that HRT, generally prescribed as menopausal hormone therapy, is associated with an increased risk of cancers of the breast, endometrium, and ovary, with the risk pattern depending on factors such as the type of therapy (oestrogen-only or combined oestrogen-progestogen), duration of treatment, and initiation according to the time of menopause. Carcinogenicity has also been established for anti-neoplastic agents used in cancer therapy, immunosuppressants, oestrogen-progestogen contraceptives, and tamoxifen. Medical use of ionising radiation, an established carcinogen, can provide major health benefits; however, prudent practices need to be in place, with procedures and techniques providing the needed diagnostic information or therapeutic gain with the lowest possible radiation exposure. For pharmaceutical drugs and medical radiation exposure with convincing evidence on their carcinogenicity, health benefits have to be balanced against the risks; potential increases in long-term cancer risk should be considered in the context of the often substantial and immediate health benefits from diagnosis and/or treatment. Thus, apart from HRT, no general recommendations on reducing cancer risk were given for carcinogenic drugs and medical radiation in the 4th edition of European Code against Cancer. It is crucial that the application of these measures relies on medical expertise and thorough benefit-risk evaluation. This also pertains to cancer-preventive drugs, and self-medication with aspirin or other potential chemopreventive drugs is strongly discouraged because of the possibility of serious, potentially lethal, adverse events. PMID:26390952

  9. Food-based Science Curriculum Increases 4th Graders Multidisciplinary Science Knowledge

    PubMed Central

    Hovland, Jana A.; Carraway-Stage, Virginia G.; Cela, Artenida; Collins, Caitlin; Díaz, Sebastián R.; Collins, Angelo; Duffrin, Melani W.

    2013-01-01

    Health professionals and policymakers are asking educators to place more emphasis on food and nutrition education. Integrating these topics into science curricula using hand-on, food-based activities may strengthen students’ understanding of science concepts. The Food, Math, and Science Teaching Enhancement Resource (FoodMASTER) Initiative is a compilation of programs aimed at using food as a tool to teach mathematics and science. Previous studies have shown that students experiencing the FoodMASTER curriculum were very excited about the activities, became increasingly interested in the subject matter of food, and were able to conduct scientific observations. The purpose of this study was to: 1) assess 4th graders food-related multidisciplinary science knowledge, and 2) compare gains in food-related science knowledge after implementation of an integrated, food-based curriculum. During the 2009–2010 school year, FoodMASTER researchers implemented a hands-on, food-based intermediate curriculum in eighteen 4th grade classrooms in Ohio (n=9) and North Carolina (n=9). Sixteen classrooms in Ohio (n=8) and North Carolina (n=8), following their standard science curricula, served as comparison classrooms. Students completed a researcher-developed science knowledge exam, consisting of 13 multiple-choice questions administered pre- and post-test. Only subjects with pre- and post-test scores were entered into the sample (Intervention n=343; Control n=237). No significant differences were observed between groups at pre-test. At post-test, the intervention group scored (9.95±2.00) significantly higher (p=.000) than the control group (8.84±2.37) on a 13-point scale. These findings suggest the FoodMASTER intermediate curriculum is more effective than a standard science curriculum in increasing students’ multidisciplinary science knowledge related to food. PMID:25152539

  10. Fluoroquinolone-gyrase-DNA complexes: two modes of drug binding.

    PubMed

    Mustaev, Arkady; Malik, Muhammad; Zhao, Xilin; Kurepina, Natalia; Luan, Gan; Oppegard, Lisa M; Hiasa, Hiroshi; Marks, Kevin R; Kerns, Robert J; Berger, James M; Drlica, Karl

    2014-05-01

    DNA gyrase and topoisomerase IV control bacterial DNA topology by breaking DNA, passing duplex DNA through the break, and then resealing the break. This process is subject to reversible corruption by fluoroquinolones, antibacterials that form drug-enzyme-DNA complexes in which the DNA is broken. The complexes, called cleaved complexes because of the presence of DNA breaks, have been crystallized and found to have the fluoroquinolone C-7 ring system facing the GyrB/ParE subunits. As expected from x-ray crystallography, a thiol-reactive, C-7-modified chloroacetyl derivative of ciprofloxacin (Cip-AcCl) formed cross-linked cleaved complexes with mutant GyrB-Cys(466) gyrase as evidenced by resistance to reversal by both EDTA and thermal treatments. Surprisingly, cross-linking was also readily seen with complexes formed by mutant GyrA-G81C gyrase, thereby revealing a novel drug-gyrase interaction not observed in crystal structures. The cross-link between fluoroquinolone and GyrA-G81C gyrase correlated with exceptional bacteriostatic activity for Cip-AcCl with a quinolone-resistant GyrA-G81C variant of Escherichia coli and its Mycobacterium smegmatis equivalent (GyrA-G89C). Cip-AcCl-mediated, irreversible inhibition of DNA replication provided further evidence for a GyrA-drug cross-link. Collectively these data establish the existence of interactions between the fluoroquinolone C-7 ring and both GyrA and GyrB. Because the GyrA-Gly(81) and GyrB-Glu(466) residues are far apart (17 Å) in the crystal structure of cleaved complexes, two modes of quinolone binding must exist. The presence of two binding modes raises the possibility that multiple quinolone-enzyme-DNA complexes can form, a discovery that opens new avenues for exploring and exploiting relationships between drug structure and activity with type II DNA topoisomerases. PMID:24497635

  11. Fluoroquinolone-gyrase-DNA complexes: two modes of drug binding.

    PubMed

    Mustaev, Arkady; Malik, Muhammad; Zhao, Xilin; Kurepina, Natalia; Luan, Gan; Oppegard, Lisa M; Hiasa, Hiroshi; Marks, Kevin R; Kerns, Robert J; Berger, James M; Drlica, Karl

    2014-05-01

    DNA gyrase and topoisomerase IV control bacterial DNA topology by breaking DNA, passing duplex DNA through the break, and then resealing the break. This process is subject to reversible corruption by fluoroquinolones, antibacterials that form drug-enzyme-DNA complexes in which the DNA is broken. The complexes, called cleaved complexes because of the presence of DNA breaks, have been crystallized and found to have the fluoroquinolone C-7 ring system facing the GyrB/ParE subunits. As expected from x-ray crystallography, a thiol-reactive, C-7-modified chloroacetyl derivative of ciprofloxacin (Cip-AcCl) formed cross-linked cleaved complexes with mutant GyrB-Cys(466) gyrase as evidenced by resistance to reversal by both EDTA and thermal treatments. Surprisingly, cross-linking was also readily seen with complexes formed by mutant GyrA-G81C gyrase, thereby revealing a novel drug-gyrase interaction not observed in crystal structures. The cross-link between fluoroquinolone and GyrA-G81C gyrase correlated with exceptional bacteriostatic activity for Cip-AcCl with a quinolone-resistant GyrA-G81C variant of Escherichia coli and its Mycobacterium smegmatis equivalent (GyrA-G89C). Cip-AcCl-mediated, irreversible inhibition of DNA replication provided further evidence for a GyrA-drug cross-link. Collectively these data establish the existence of interactions between the fluoroquinolone C-7 ring and both GyrA and GyrB. Because the GyrA-Gly(81) and GyrB-Glu(466) residues are far apart (17 Å) in the crystal structure of cleaved complexes, two modes of quinolone binding must exist. The presence of two binding modes raises the possibility that multiple quinolone-enzyme-DNA complexes can form, a discovery that opens new avenues for exploring and exploiting relationships between drug structure and activity with type II DNA topoisomerases.

  12. PREFACE: 4th International Symposium on Instrumentation Science and Technology (ISIST'2006)

    NASA Astrophysics Data System (ADS)

    Jiubin, Tan

    2006-10-01

    On behalf of the International Program Committee of ISIST'2006 and the symposium coordinators, I would like to thank all the participants for their presence at the 4th International Symposium on Instrumentation Science and Technology (ISIST'2006), a platform for scientists, researchers and experts from different parts of the world to present their achievements and to exchange their views on ways and means to further develop modern instrumentation science and technology. In the present information age, instrumentation science and technology is playing a more and more important role, not only in the acquisition and conversion of information at the very beginning of the information transformation chain, but also in the transfer, manipulation and utilization of information. It provides an analysis and test means for bioengineering, medical engineering, life science, environmental engineering and micro/nanometer technology, and integrates these disciplines to form new subdivisions of their own. The major subject of the symposium is crossover and fusion between instrumentation science and technology and other sciences and technologies. ISIST'2006 received more than 800 full papers from 12 countries and regions, from which 300 papers were finally selected by the international program committee for inclusion in the proceedings of ISIST'2006, published in 2 volumes. The major topics include instrumentation basic theory and methodology, sensors and conversion technology, signal and image processing, instruments and systems, laser and optical fiber instrumentation, advanced optical instrumentation, optoelectronics instrumentation, MEMS, nanotechnology and instrumentation, biomedical and environmental instrumentation, automatic test and control. The International Symposium on Instrumentation Science and Technology (ISIST) is sponsored by ICMI, NSFC, CSM, and CIS, and organized by ICMI, HIT and IC-CSM, and held every two years. The 1st symposium was held in LuoYang, China in

  13. PREFACE: 4th International Conference on Safe Production and Use of Nanomaterials (Nanosafe2014)

    NASA Astrophysics Data System (ADS)

    Tardif, F.; Damlencourt, J.-F.; Schuster, F.; Gaultier, V.

    2015-05-01

    This volume contains a collection of contributions presented at the 4th International Conference on Safe Production and Use of Nanomaterials (NANOSAFE 2014) held in Grenoble, France, from 18th to 20th November 2014. The issues of fast progress in the field of Nanosafety are up to the potential benefits that nanotechnology can bring to mankind. Making more efficient - more sustainable - easier to share mineral resources, increasing the yields of new energy technologies, enabling drugs that act selectively and locally are just few examples of the wide range of nanomaterial applications that currently benefit humanity. Nevertheless, the dynamic development of nanomaterials requires the adhesion from the general public who rightly demand major progresses in Nanosafety as a prerequisite. This is our exciting responsibility and challenge! Following the successful outcome of the three past international conferences on safe production and use of nanomaterials: Nanosafe 2008, 2010 and 2012, the organizing committee has the pleasure to welcoming you again to Minatec, Grenoble with some of the most famous specialists in the field. This year, two new topics have been added dealing with the "New Application of Nanomaterials" and "Nano-responsible Development" in addition to the usual issues addressed in previous Nanosafe conferences such as Expology, Detection and Characterization, Toxicology, Environmental Interactions, Nanomaterials Release, Life Cycle Analysis, Regulation and Standardization, Risk Management. The debates in 2012 proved highly successful so this formula has been kept in 2014 with 3 round tables: Nano-Responsible Development, Risks and Benefits for the Environment, Toxicology Progress. In this 4th edition, there were more than 330 registered participants from 28 different countries including 160 oral presentation covering the whole Nanosafety issues in 12 sessions, satellite workshops and round tables. This high number of participants makes this edition one of

  14. A Teaching Model for Scaffolding 4th Grade Students' Scientific Explanation Writing

    NASA Astrophysics Data System (ADS)

    Yang, Hsiu-Ting; Wang, Kuo-Hua

    2014-08-01

    Improving students scientific explanations is one major goal of science education. Both writing activities and concept mapping are reported as effective strategies for enhancing student learning of science. The purpose of this study was to examine the effect of a teaching model, named the DCI model, which integrates a Descriptive explanation writing activity, Concept mapping, and an Interpretive explanation writing activity, is introduced in a 4th grade science class to see if it would improve students' scientific explanations and understanding. A quasi-experimental design, including a non-randomized comparison group and a pre- and post-test design, was adopted for this study. An experimental group of 25 students were taught using the DCI teaching model, while a comparison group received a traditional lecture teaching. A rubric and content analysis was used to assess students' scientific explanations. The independent sample t test was used to measure difference in conceptual understanding between the two groups, before and after instruction. Then, the paired t test analysis was used to understand the promotion of the DCI teaching model. The results showed that students in the experimental group performed better than students in the comparison group, both in scientific concept understanding and explanation. Suggestions for using concept mapping and writing activities (the DCI teaching model) in science classes are provided in this study.

  15. 4th-International Symposium on Ultrafast Surface Science - Final Report

    SciTech Connect

    Hrvoje Petek

    2005-01-26

    The 4-th International Symposium on Ultrafast Surface Dynamics (UDS4) was held at the Telluride Summer Research Center on June 22-27, 2003. The International Organizing Committee consisting of Hrvoje Petek (USA), Xiaoyang Zhu (USA), Pedro Echenique (Spain) and Maki Kawai (Japan) brought together a total of 51 participants 16 of whom were from Europe, 10 from Japan, and 25 from the USA. The focus of the conference was on ultrafast electron or light induced processes at well-defined surfaces. Ultrafast surface dynamics concerns the transfer of charge and energy at solid surfaces on the femtosecond time scale. These processes govern rates of fundamental steps in surface reactions, interfacial electron transfer in molecular electronics, and relaxation in spin transport. Recent developments in femtosecond laser technology make it possible to measure by a variety of nonlinear optical techniques directly in the time domain the microscopic rates underlying these interfacial processes. Parallel progress in scanning probe microscopy makes it possible at a single molecular level to perform the vibrational and electronic spectroscopy measurements, to induce reactions with tunneling electrons, and to observe their outcome. There is no doubt that successful development in the field of ultrafast surface dynamics will contribute to many important disciplines.

  16. The 4th Annual Meeting of the American Society for Nanomedicine.

    PubMed

    Gendelman, Howard E; Balogh, Lajos P; Bawa, Raj; Bradbury, Michelle; Chang, Esther H; Chiu, Wah; Farokhzad, Omid; Foldvari, Marianna; Lanza, Gregory; Wang, Kuan

    2014-03-01

    The 4th Conference of the American Society for Nanomedicine is being held March 28-30, 2014 at the Universities at Shady Grove, Rockville, Maryland. The meeting's theme is on defining the role of nanomedicines for nervous system diagnostics and disease but balanced by broad and timely topics for nanotechnology. Nanoneuromedicine, as defined by the development of small drug formulations for the diagnosis and treatment of degenerative, inflammatory, infectious, vascular, addictive, behavioral and metabolic disorders of the nervous system, will provide a focus for each of the scientific sessions. This research is interdisciplinary and it's in its infancy. The hurdles that preclude translation from bench to bedside would include its delivery across the blood brain barrier, limiting nervous system toxicities, and improving drug targeting to diseased brain subregions. These all pose challenges. Multidisciplinary works in neuroscience (neurobiology, neurochemistry, neurophysiology, and neuroinflammation), bioimaging, and polymer chemistry to facilitate outcomes for formulation manufacture will be vigorously discussed. How drugs reach sites of action need include neural cell specific subcellular compartments. The ASNM meeting will showcase nanoneuromedicine research from leading investigators of divergent scientific backgrounds who define this new field. It will also serve as an incubator for developing investigators and broad new field discoveries. Welcome to the conference and enjoy!

  17. Need for Specific Sugar-Sweetened Beverage Lessons for 4th and 5th Graders

    PubMed Central

    Bea, Jennifer W.; Jacobs, Laurel; Waits, Juanita; Hartz, Vern; Martinez, Stephanie H.; Standfast, Rebecca D.; Farrell, Vanessa A.; Bawden, Margine; Whitmer, Evelyn; Misner, Scottie

    2015-01-01

    Objective Consumption of sugar-sweetened beverages (SSB) is linked to obesity. We hypothesized that school-based nutrition education would decrease SSB consumption. Design Self-selected interventional cohort with random selection for pre and post measurements Setting Arizona SNAP-Ed eligible schools Participants Randomly selected (9%) 4th and 5th grade classroom students Intervention The University of Arizona Nutrition Network (UANN) provided general nutrition education training and materials to teachers, to be delivered to their students. The UANN administered behavioral questionnaires to students in both Fall and Spring. Main Outcome Measure(s) Change in SSB consumption Analyses Descriptive statistics were computed for student demographics and beverage consumption on the day prior to testing. Paired t-tests evaluated change in classroom averages. Linear regression assessed potential correlates of SSB consumption. Results Fall mean SSB consumption was 1.1 (±0.2) times; mean milk and water intake were 1.6 (±0.2) and 5.2 (±0.7) times, respectively. Beverage consumption increased (3.2%) in springtime, with increased SSBs (14.4%) accounting for the majority (p=0.006). Change in SSB consumption was negatively associated with baseline SSB and water consumption, but positively associated with baseline milk fat (p≤0.05). Conclusions and Implications The results suggest the need for beverage specific education to encourage children to consume more healthful beverages in warmer weather. PMID:25239840

  18. Project ASTRO: Local Coalitions for Bringing Astronomers to 4th - 9th Grade Classrooms

    NASA Astrophysics Data System (ADS)

    Fraknoi, Andrew

    1998-05-01

    We report on Project ASTRO, an NSF and NASA funded program that now links professional and amateur astronomers with local 4th through 9th grade teachers in 10 sites around the country. Each site matches and trains about 20-25 astronomer-teacher partnerships per year, focusing on hands-on, age-appropriate activities, demonstrations of the scientific method, as well as family and community outreach. Over 10,000 copies of the project's 813-page UNIVERSE AT YOUR FINGERTIPS resource and activity notebook (published by the A.S.P) are now in use in educational institututions around the world. The project's HOW-TO-MANUAL is being used as a practical guide to establishing astronomer-teacher partnerships where no formal ASTRO site exists, and a 12-minute video explaining and demonstrating the project is also available. In each of the ten sites, a coalition of educational and scientific institutions is assisting the project with in-kind donations, publicity, personnel, training, materials, etc. We are conducting an experiment (at the behest of NSF) to see to what degree the sites can become self-supporting over time. (One site, in Salt Lake City, has already received full funding from a local foundation.) We will discuss the progress of the project and will have a variety of sample materials available, including our annotated catalog of national astronomy and space science education projects (see associated URL).

  19. Multiwavelength Analysis of a Moving Type-IV Radio Burst on 4th March 2012

    NASA Astrophysics Data System (ADS)

    Veluchamy, V.; Chen, Y.; Feng, S.; Du, G.; Song, H.; Kong, X.

    2015-12-01

    We performed a multiwavelength analysis of a moving Type-IV radio burst on 4th march 2012. The Type-IV radio burst is observed between 10:39 - 11:00 UT in the frequency range of 300 - 20 MHz. From the radio heliographic observation, the radio source of the type-IV burst is traced and their sky plane speed is estimated as ~ 370 km/s. A plasmoid structure is ejected during the impulsive phase of the flare, at the same time of the type-IV burst and the structure is clearly observed at SDO/AIA 131 Å channel. From this, we find that the radio source moves with the plasmoid. The high brightness temperature profile in the range of 108 - 109 K and the moderate polarization between -50 - 30 % supports the plasma emission mechanism. Further the differential emission measure (DEM) analysis will be carried out and their results will be presented to provide more evidence of the emission mechanism.

  20. European Code against Cancer 4th Edition: Ionising and non-ionising radiation and cancer.

    PubMed

    McColl, Neil; Auvinen, Anssi; Kesminiene, Ausrele; Espina, Carolina; Erdmann, Friederike; de Vries, Esther; Greinert, Rüdiger; Harrison, John; Schüz, Joachim

    2015-12-01

    Ionising radiation can transfer sufficient energy to ionise molecules, and this can lead to chemical changes, including DNA damage in cells. Key evidence for the carcinogenicity of ionising radiation comes from: follow-up studies of the survivors of the atomic bombings in Japan; other epidemiological studies of groups that have been exposed to radiation from medical, occupational or environmental sources; experimental animal studies; and studies of cellular responses to radiation. Considering exposure to environmental ionising radiation, inhalation of naturally occurring radon is the major source of radiation in the population - in doses orders of magnitude higher than those from nuclear power production or nuclear fallout. Indoor exposure to radon and its decay products is an important cause of lung cancer; radon may cause approximately one in ten lung cancers in Europe. Exposures to radon in buildings can be reduced via a three-step process of identifying those with potentially elevated radon levels, measuring radon levels, and reducing exposure by installation of remediation systems. In the 4th Edition of the European Code against Cancer it is therefore recommended to: "Find out if you are exposed to radiation from naturally high radon levels in your home. Take action to reduce high radon levels". Non-ionising types of radiation (those with insufficient energy to ionise molecules) - including extremely low-frequency electric and magnetic fields as well as radiofrequency electromagnetic fields - are not an established cause of cancer and are therefore not addressed in the recommendations to reduce cancer risk. PMID:26126928

  1. 4th annual primary care ethics conference: ethics education and lifelong learning

    PubMed Central

    Spicer, John; McKenzie-Edwards, Emma; Misselbrook, David

    2014-01-01

    Primary care ethics is a field of study that has recently found new life, with calls to establish the relevance of ethical discussion in general practice, to gather a body of literature and to carve out an intellectual space for primary care on the academic landscape of bioethics. In this report, we reflect on the key strands of the 4th primary care ethics conference held at the Royal Society of Medicine, on a theme of ethics education and lifelong learning: first, to produce insights that have relevance for policy and practice; and second, to illustrate the idea that not only is ethics relevant in primary care, but primary care is relevant in medical ethics. Core themes included the advantages and disadvantages of prescriptive ways of doing ethics in education, ethical reflection and potential risk to professional status, the need to deal with societal change and to take on board the insights gained from empirical work, whether this is about different kinds of fatherhood, or work on the causes of moral distress in healthcare workers. PMID:25949739

  2. European Code against Cancer 4th Edition: 12 ways to reduce your cancer risk.

    PubMed

    Schüz, Joachim; Espina, Carolina; Villain, Patricia; Herrero, Rolando; Leon, Maria E; Minozzi, Silvia; Romieu, Isabelle; Segnan, Nereo; Wardle, Jane; Wiseman, Martin; Belardelli, Filippo; Bettcher, Douglas; Cavalli, Franco; Galea, Gauden; Lenoir, Gilbert; Martin-Moreno, Jose M; Nicula, Florian Alexandru; Olsen, Jørgen H; Patnick, Julietta; Primic-Zakelj, Maja; Puska, Pekka; van Leeuwen, Flora E; Wiestler, Otmar; Zatonski, Witold

    2015-12-01

    This overview describes the principles of the 4th edition of the European Code against Cancer and provides an introduction to the 12 recommendations to reduce cancer risk. Among the 504.6 million inhabitants of the member states of the European Union (EU28), there are annually 2.64 million new cancer cases and 1.28 million deaths from cancer. It is estimated that this cancer burden could be reduced by up to one half if scientific knowledge on causes of cancer could be translated into successful prevention. The Code is a preventive tool aimed to reduce the cancer burden by informing people how to avoid or reduce carcinogenic exposures, adopt behaviours to reduce the cancer risk, or to participate in organised intervention programmes. The Code should also form a base to guide national health policies in cancer prevention. The 12 recommendations are: not smoking or using other tobacco products; avoiding second-hand smoke; being a healthy body weight; encouraging physical activity; having a healthy diet; limiting alcohol consumption, with not drinking alcohol being better for cancer prevention; avoiding too much exposure to ultraviolet radiation; avoiding cancer-causing agents at the workplace; reducing exposure to high levels of radon; encouraging breastfeeding; limiting the use of hormone replacement therapy; participating in organised vaccination programmes against hepatitis B for newborns and human papillomavirus for girls; and participating in organised screening programmes for bowel cancer, breast cancer, and cervical cancer. PMID:26164654

  3. European Code against Cancer 4th Edition: Ultraviolet radiation and cancer.

    PubMed

    Greinert, Rüdiger; de Vries, Esther; Erdmann, Friederike; Espina, Carolina; Auvinen, Anssi; Kesminiene, Ausrele; Schüz, Joachim

    2015-12-01

    Ultraviolet radiation (UVR) is part of the electromagnetic spectrum emitted naturally from the sun or from artificial sources such as tanning devices. Acute skin reactions induced by UVR exposure are erythema (skin reddening), or sunburn, and the acquisition of a suntan triggered by UVR-induced DNA damage. UVR exposure is the main cause of skin cancer, including cutaneous malignant melanoma, basal-cell carcinoma, and squamous-cell carcinoma. Skin cancer is the most common cancer in fair-skinned populations, and its incidence has increased steeply over recent decades. According to estimates for 2012, about 100,000 new cases of cutaneous melanoma and about 22,000 deaths from it occurred in Europe. The main mechanisms by which UVR causes cancer are well understood. Exposure during childhood appears to be particularly harmful. Exposure to UVR is a risk factor modifiable by individuals' behaviour. Excessive exposure from natural sources can be avoided by seeking shade when the sun is strongest, by wearing appropriate clothing, and by appropriately applying sunscreens if direct sunlight is unavoidable. Exposure from artificial sources can be completely avoided by not using sunbeds. Beneficial effects of sun or UVR exposure, such as for vitamin D production, can be fully achieved while still avoiding too much sun exposure and the use of sunbeds. Taking all the scientific evidence together, the recommendation of the 4th edition of the European Code Against Cancer for ultraviolet radiation is: "Avoid too much sun, especially for children. Use sun protection. Do not use sunbeds." PMID:26096748

  4. Effectiveness of fenbendazole against later 4th-stage Strongylus vulgaris in ponies.

    PubMed

    Slocombe, J O; McCraw, B M; Pennock, P W; Baird, J D

    1983-12-01

    Twelve pony foals (reared worm-free) were inoculated with Strongylus vulgaris. Approximately 8 weeks later, 4 of the foals were given fenbendazole (10% suspension) at a dosage rate of 10 mg/kg of body weight daily for 5 days and 4 foals were given the suspension at a dosage rate of 50 mg/kg daily for 3 days; the remaining foals were given a placebo. All treatments were administered by stomach tube. Fenbendazole was 99.6 and 97.9% effective in the 2 treatment groups, respectively, in eliminating later 4th-stage S vulgaris larvae located near the origin of major intestinal arteries. On microscopic examination of the ileocolic artery from fenbendazole-treated foals, a few larval remnants were found beneath the tunica intima in small organized mural thrombi overgrown with endothelium. It would appear that larvae are rapidly destroyed after administration of fenbendazole. A pony foal reared on pasture and with arteriographic evidence of arteritis of the cranial mesenteric and ileocolic arteries was treated with fenbendazole (10% suspension) by stomach tube at a dosage rate of 50 mg/kg of body weight daily for 3 days. By arteriographic examination made 4 weeks later, there was evidence of regression of the lesion, and at necropsy done a week later, there was no arteritis or larvae in the lumen of those arteries.

  5. European Code against Cancer 4th Edition: Ultraviolet radiation and cancer.

    PubMed

    Greinert, Rüdiger; de Vries, Esther; Erdmann, Friederike; Espina, Carolina; Auvinen, Anssi; Kesminiene, Ausrele; Schüz, Joachim

    2015-12-01

    Ultraviolet radiation (UVR) is part of the electromagnetic spectrum emitted naturally from the sun or from artificial sources such as tanning devices. Acute skin reactions induced by UVR exposure are erythema (skin reddening), or sunburn, and the acquisition of a suntan triggered by UVR-induced DNA damage. UVR exposure is the main cause of skin cancer, including cutaneous malignant melanoma, basal-cell carcinoma, and squamous-cell carcinoma. Skin cancer is the most common cancer in fair-skinned populations, and its incidence has increased steeply over recent decades. According to estimates for 2012, about 100,000 new cases of cutaneous melanoma and about 22,000 deaths from it occurred in Europe. The main mechanisms by which UVR causes cancer are well understood. Exposure during childhood appears to be particularly harmful. Exposure to UVR is a risk factor modifiable by individuals' behaviour. Excessive exposure from natural sources can be avoided by seeking shade when the sun is strongest, by wearing appropriate clothing, and by appropriately applying sunscreens if direct sunlight is unavoidable. Exposure from artificial sources can be completely avoided by not using sunbeds. Beneficial effects of sun or UVR exposure, such as for vitamin D production, can be fully achieved while still avoiding too much sun exposure and the use of sunbeds. Taking all the scientific evidence together, the recommendation of the 4th edition of the European Code Against Cancer for ultraviolet radiation is: "Avoid too much sun, especially for children. Use sun protection. Do not use sunbeds."

  6. European Code against Cancer 4th Edition: Ionising and non-ionising radiation and cancer.

    PubMed

    McColl, Neil; Auvinen, Anssi; Kesminiene, Ausrele; Espina, Carolina; Erdmann, Friederike; de Vries, Esther; Greinert, Rüdiger; Harrison, John; Schüz, Joachim

    2015-12-01

    Ionising radiation can transfer sufficient energy to ionise molecules, and this can lead to chemical changes, including DNA damage in cells. Key evidence for the carcinogenicity of ionising radiation comes from: follow-up studies of the survivors of the atomic bombings in Japan; other epidemiological studies of groups that have been exposed to radiation from medical, occupational or environmental sources; experimental animal studies; and studies of cellular responses to radiation. Considering exposure to environmental ionising radiation, inhalation of naturally occurring radon is the major source of radiation in the population - in doses orders of magnitude higher than those from nuclear power production or nuclear fallout. Indoor exposure to radon and its decay products is an important cause of lung cancer; radon may cause approximately one in ten lung cancers in Europe. Exposures to radon in buildings can be reduced via a three-step process of identifying those with potentially elevated radon levels, measuring radon levels, and reducing exposure by installation of remediation systems. In the 4th Edition of the European Code against Cancer it is therefore recommended to: "Find out if you are exposed to radiation from naturally high radon levels in your home. Take action to reduce high radon levels". Non-ionising types of radiation (those with insufficient energy to ionise molecules) - including extremely low-frequency electric and magnetic fields as well as radiofrequency electromagnetic fields - are not an established cause of cancer and are therefore not addressed in the recommendations to reduce cancer risk.

  7. PREFACE: 4th National Conference on Processing and Characterization of Materials (NCPCM 2014)

    NASA Astrophysics Data System (ADS)

    2015-02-01

    This volume contains selected full length technical papers amongst forty oral presentations made in the 4th National Conference on Processing and Characterization of Materials (NCPCM 2014), NIT Rourkela, Rourkela, Odisha, India, December 5 - 6, 2014. The first conference of the NCPCM series was held at the same place in December 2011. Seeing the enthusiasm of the participants, it was decided to organize such conference in Rourkela every year. The basic idea was to establish a periodical national forum for multi-scale approaches in processing and characterization of materials in the eastern part of India. The conference NCPCM 2014 has successfully carried the tradition of previous conferences; more than fifty participants from twenty different organizations across India have registered. The conference was consisted of six technical sessions of about fifty contributory talks along with three keynote lectures. A metallography contest was also organized during the event. Out of these, thirty four best peer-reviewed contributions are published in this volume of IOP Conference Series: Materials Science and Engineering. We would like to thank all the contributors, members of the organizing committee, session chairs as well as colleagues and students who helped with the preparation of the conference and, particularly, with the preparation of this volume. We convey our heartiest gratitude to the sponsors and advertisers for their contribution.

  8. The relationship between the carrying angle and the distal extent of the 2nd and 4th fingertips.

    PubMed

    Sönmez, M; Tattemur, Y; Karacan, K; Erdal, M

    2012-08-01

    The angle towards the lateral side between the arm and forearm when the forearm is in full extension and supination is defined as the carrying angle. It is well known that the 2nd finger is longer in women whereas the 4th finger is longer in men, due to in-utero hormonal effects. In the present study, the relationship between the carrying angle and the distal extent of the 2nd and 4th fingertips is studied. The findings reveal that the carrying angle was greater both in left and right sides in women than in men. In addition, while the distal extent of the 2nd fingertips was longer in women, the 4th fingertip was longer in men. There was a moderately positive correlation between the carrying angle and the distal fingertip lengths. Therefore, it could be suggested that the morphometric factors play role on the distal extent of the fingertips other than the hormonal effects.

  9. Weak Mutators Can Drive the Evolution of Fluoroquinolone Resistance in Escherichia coli

    PubMed Central

    Örlén, Hanna; Hughes, Diarmaid

    2006-01-01

    Weak mutators are common among clinical isolates of Escherichia coli. We show that the relative mutation rate and the “evolvability of fluoroquinolone resistance” are related by a power law slope of 1.2 over 3 orders of magnitude. Thus, even weak mutators can drive the evolution of fluoroquinolone resistance under selection pressure. PMID:17005830

  10. Weak mutators can drive the evolution of fluoroquinolone resistance in Escherichia coli.

    PubMed

    Orlén, Hanna; Hughes, Diarmaid

    2006-10-01

    Weak mutators are common among clinical isolates of Escherichia coli. We show that the relative mutation rate and the "evolvability of fluoroquinolone resistance" are related by a power law slope of 1.2 over 3 orders of magnitude. Thus, even weak mutators can drive the evolution of fluoroquinolone resistance under selection pressure.

  11. Evaluation of Ciprofloxacin as a Representative of Veterinary Fluoroquinolones in Susceptibility Testing

    PubMed Central

    Riddle, Christa; Lemons, Carol L.; Papich, Mark G.; Altier, Craig

    2000-01-01

    Currently in veterinary medicine, ciprofloxacin is often used in susceptibility testing to represent the entire class of fluoroquinolone antimicrobials. Using quality control organisms as well as clinical isolates, we compared the MIC of ciprofloxacin to those of three other fluoroquinolones used in animals and found that ciprofloxacin is not an adequate representative of other members of this class. PMID:10747156

  12. Crystal structure and stability of gyrase–fluoroquinolone cleaved complexes from Mycobacterium tuberculosis

    PubMed Central

    Williamson, Benjamin H.; Kerns, Robert J.; Berger, James M.

    2016-01-01

    Mycobacterium tuberculosis (Mtb) infects one-third of the world’s population and in 2013 accounted for 1.5 million deaths. Fluoroquinolone antibacterials, which target DNA gyrase, are critical agents used to halt the progression from multidrug-resistant tuberculosis to extensively resistant disease; however, fluoroquinolone resistance is emerging and new ways to bypass resistance are required. To better explain known differences in fluoroquinolone action, the crystal structures of the WT Mtb DNA gyrase cleavage core and a fluoroquinolone-sensitized mutant were determined in complex with DNA and five fluoroquinolones. The structures, ranging from 2.4- to 2.6-Å resolution, show that the intrinsically low susceptibility of Mtb to fluoroquinolones correlates with a reduction in contacts to the water shell of an associated magnesium ion, which bridges fluoroquinolone–gyrase interactions. Surprisingly, the structural data revealed few differences in fluoroquinolone–enzyme contacts from drugs that have very different activities against Mtb. By contrast, a stability assay using purified components showed a clear relationship between ternary complex reversibility and inhibitory activities reported with cultured cells. Collectively, our data indicate that the stability of fluoroquinolone/DNA interactions is a major determinant of fluoroquinolone activity and that moieties that have been appended to the C7 position of different quinolone scaffolds do not take advantage of specific contacts that might be made with the enzyme. These concepts point to new approaches for developing quinolone-class compounds that have increased potency against Mtb and the ability to overcome resistance. PMID:26792525

  13. Terbium-sensitized luminescence screening method for fluoroquinolones in beef serum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Enrofloxacin is one of only two fluoroquinolone antibiotics approved for use in cattle in the U.S. Microbial screening methods commonly used for monitoring veterinary drug residues are not sensitive or selective for fluoroquinolones. In this work, a luminescence-based screening assay was developed...

  14. Fluoroquinolone-induced serious, persistent, multisymptom adverse effects.

    PubMed

    Golomb, Beatrice Alexandra; Koslik, Hayley Jean; Redd, Alan J

    2015-10-05

    We present a case series of four previously healthy, employed adults without significant prior medical history in each of whom symptoms developed while on fluoroquinolones (FQs), with progression that continued following discontinuation evolving to a severe, disabling multisymptom profile variably involving tendinopathy, muscle weakness, peripheral neuropathy, autonomic dysfunction, sleep disorder, cognitive dysfunction and psychiatric disturbance. Physicians and patients should be alert to the potential for FQ-induced severe disabling multisymptom pathology that may persist and progress following FQ use. Known induction by FQs of delayed mitochondrial toxicity provides a compatible mechanism, with symptom profiles (and documented mechanisms of FQ toxicity) compatible with the hypothesis of an exposure-induced mitochondrial neurogastrointestinal encephalomyopathy.

  15. Resistance to fluoroquinolones and methicillin in ophthalmic isolates of Staphylococcus pseudintermedius from companion animals

    PubMed Central

    Kang, Min-Hee; Chae, Min-Joo; Yoon, Jang-Won; Lee, So-Young; Yoo, Jong-Hyun; Park, Hee-Myung

    2014-01-01

    Resistance to fluoroquinolones and methicillin was determined for 49 ophthalmic isolates of Staphylococcus pseudintermedius from dogs with and without ophthalmic disease. Resistance was observed for ciprofloxacin (40.8%), ofloxacin (38.8%), enrofloxacin (38.8%), levofloxacin (34.7%), and moxifloxacin (4.1%). Eighteen isolates, 16 of which were resistant to oxacillin, were mecA-positive. Nine of the 16 oxacillin-resistant mecA-positive S. pseudintermedius isolates were resistant to more than one fluoroquinolone and 2 isolates were resistant to 5 fluoroquinolones. The frequency of mecA gene occurrence and fluoroquinolone resistance was twice as high among S. pseudintermedius isolates derived from dogs with ophthalmic disease compared with isolates for dogs without ophthalmic disease. The high prevalence of methicillin and fluoroquinolone resistance in S. pseudintermedius from dogs with ophthalmic disease is a concern. PMID:24982521

  16. Resistance to fluoroquinolones and methicillin in ophthalmic isolates of Staphylococcus pseudintermedius from companion animals.

    PubMed

    Kang, Min-Hee; Chae, Min-Joo; Yoon, Jang-Won; Lee, So-Young; Yoo, Jong-Hyun; Park, Hee-Myung

    2014-07-01

    Resistance to fluoroquinolones and methicillin was determined for 49 ophthalmic isolates of Staphylococcus pseudintermedius from dogs with and without ophthalmic disease. Resistance was observed for ciprofloxacin (40.8%), ofloxacin (38.8%), enrofloxacin (38.8%), levofloxacin (34.7%), and moxifloxacin (4.1%). Eighteen isolates, 16 of which were resistant to oxacillin, were mecA-positive. Nine of the 16 oxacillin-resistant mecA-positive S. pseudintermedius isolates were resistant to more than one fluoroquinolone and 2 isolates were resistant to 5 fluoroquinolones. The frequency of mecA gene occurrence and fluoroquinolone resistance was twice as high among S. pseudintermedius isolates derived from dogs with ophthalmic disease compared with isolates for dogs without ophthalmic disease. The high prevalence of methicillin and fluoroquinolone resistance in S. pseudintermedius from dogs with ophthalmic disease is a concern. PMID:24982521

  17. Learning Natural Selection in 4th Grade with Multi-Agent-Based Computational Models

    NASA Astrophysics Data System (ADS)

    Dickes, Amanda Catherine; Sengupta, Pratim

    2013-06-01

    In this paper, we investigate how elementary school students develop multi-level explanations of population dynamics in a simple predator-prey ecosystem, through scaffolded interactions with a multi-agent-based computational model (MABM). The term "agent" in an MABM indicates individual computational objects or actors (e.g., cars), and these agents obey simple rules assigned or manipulated by the user (e.g., speeding up, slowing down, etc.). It is the interactions between these agents, based on the rules assigned by the user, that give rise to emergent, aggregate-level behavior (e.g., formation and movement of the traffic jam). Natural selection is such an emergent phenomenon, which has been shown to be challenging for novices (K16 students) to understand. Whereas prior research on learning evolutionary phenomena with MABMs has typically focused on high school students and beyond, we investigate how elementary students (4th graders) develop multi-level explanations of some introductory aspects of natural selection—species differentiation and population change—through scaffolded interactions with an MABM that simulates predator-prey dynamics in a simple birds-butterflies ecosystem. We conducted a semi-clinical interview based study with ten participants, in which we focused on the following: a) identifying the nature of learners' initial interpretations of salient events or elements of the represented phenomena, b) identifying the roles these interpretations play in the development of their multi-level explanations, and c) how attending to different levels of the relevant phenomena can make explicit different mechanisms to the learners. In addition, our analysis also shows that although there were differences between high- and low-performing students (in terms of being able to explain population-level behaviors) in the pre-test, these differences disappeared in the post-test.

  18. PREFACE: 4th International Conference on: Preservation and Conservation Issues in Digital Printing and Digital Photography

    NASA Astrophysics Data System (ADS)

    Fricker, A.; Green, P.

    2010-04-01

    These conference proceedings contain the written papers of the contributions presented at the 4th International Conference on: Preservation and Conservation Issues in Digital Printing and Digital Photography. The conference was held at the Institute of Physics, London, UK on 27th-28th May 2010. Previous conferences in this series took place in 2000, 2003 and 2006. The aim of this conference series is to inform those responsible for the preservation of digitally printed materials about developments in digital photography and printing technologies. We aim to examine progress in research on inks and substrates and their significance for conservation and preservation issues and techniques. We also hope to develop links between related industries and the conservation/preservation world. Research areas explored in this conference include current developments and future trends in digital printing and photographic technologies; the effect of environmental, storage and salvage conditions on the durability of digital prints and photographs; image processing techniques; image permanence considerations and standards for fastness, permanence and the role of scanning and file formats. We would like to thank all participants for their contribution to the conference programme and these proceedings. Our thanks go to Ms C. Gu and Mr M. Sandy for chairing conference sessions. We are also grateful to Dawn Stewart and the Institute of Physics Conference Team for their invaluable support and assistance in arranging the conference and reception. Finally we would like to extend our thanks to the Society of Imaging Science and Technology (IS&T) for their sponsorship support. The Editors Acknowledgements Conference Organising Committee: Ms A Fricker and Dr. P Green (London College of Communication, University of the Arts London). Proceedings edited and compiled by Ms A Fricker and Dr. P Green.

  19. European Code against Cancer 4th Edition: Environment, occupation and cancer.

    PubMed

    Espina, Carolina; Straif, Kurt; Friis, Søren; Kogevinas, Manolis; Saracci, Rodolfo; Vainio, Harri; Schüz, Joachim

    2015-12-01

    People are exposed throughout life to a wide range of environmental and occupational pollutants from different sources at home, in the workplace or in the general environment - exposures that normally cannot be directly controlled by the individual. Several chemicals, metals, dusts, fibres, and occupations have been established to be causally associated with an increased risk of specific cancers, such as cancers of the lung, skin and urinary bladder, and mesothelioma. Significant amounts of air pollutants - mainly from road transport and industry - continue to be emitted in the European Union (EU); an increased occurrence of lung cancer has been attributed to air pollution even in areas below the EU limits for daily air pollution. Additionally, a wide range of pesticides as well as industrial and household chemicals may lead to widespread human exposure, mainly through food and water. For most environmental pollutants, the most effective measures are regulations and community actions aimed at reducing and eliminating the exposures. Thus, it is imperative to raise awareness about environmental and occupational carcinogens in order to motivate individuals to be proactive in advocating protection and supporting initiatives aimed at reducing pollution. Regulations are not homogeneous across EU countries, and protective measures in the workplace are not used consistently by all workers all the time; compliance with regulations needs to be continuously monitored and enforced. Therefore, the recommendation on Environment and Occupation of the 4th edition of the European Code against Cancer, focusing on what individuals can do to reduce their cancer risk, reads: "In the workplace, protect yourself against cancer-causing substances by following health and safety instructions."

  20. PREFACE: 4th International Workshop on Statistical Physics and Mathematics for Complex Systems (SPMCS)

    NASA Astrophysics Data System (ADS)

    Wang, Alexandre; Abe, Sumiyoshi; Li, Wei

    2015-04-01

    This volume contains 24 contributed papers presented at the 4th International Workshop on Statistical Physics and Mathematics for Complex Systems (SPMCS) held during October 12-16, 2014 in Yichang, China. Each paper was peer-reviewed by at least one referee chosen from a distinguished international panel. The previous three workshops of this series were organized in 2008, 2010, and 2012, in Le Mans, France, Wuhan, China, and Kazan, Russia, respectively. The SPMCS international workshop series is destined mainly to communicate and exchange research results and information on the fundamental challenges and questions in the vanguard of statistical physics, thermodynamics and mathematics for complex systems. More specifically, the topics of interest touch, but are not limited to, the following: • Fundamental aspects in the application of statistical physics and thermodynamics to complex systems and their modeling • Finite size and non-extensive system • Fluctuation theorems and equalities, quantum thermodynamics • Variational principle for random dynamics • Fractal geometry, fractional mathematics More than 50 participants from 7 countries participated in SPMCS-2014. 35 oral contributions were presented at the workshop. We would like to take this opportunity to thank the members of the Scientific Program Committee, many of whom acted as reviewers of the papers and responded promptly. We would also like to thank the organizing committee, the session chairs, the technicians and the students for the smooth running of the whole workshop. Thanks also go to China Three Gorges University who provided generous support for the conference venue, as well as exquisite refreshments for the tea breaks. The workshop was also partially supported by Central China Normal University and the Programme of Introducing Talents of Discipline to Universities under grant NO. B08033. Special thanks are due to Ms Juy Zhu who has done excellent editing work with great effort.

  1. The Ratio of 2nd to 4th Digit Length in Korean Alcohol-dependent Patients

    PubMed Central

    Han, Changwoo; Bae, Hwallip; Lee, Yu-Sang; Won, Sung-Doo; Kim, Dai Jin

    2016-01-01

    Objective The ratio of 2nd to 4th digit length (2D:4D) is a sexually dimorphic trait. Men have a relatively shorter second digit than fourth digit. This ratio is thought to be influenced by higher prenatal testosterone level or greater sensitivity to androgen. The purpose of this study is to investigate the relationship between alcohol dependence and 2D:4D in a Korean sample and whether 2D:4D can be a biologic marker in alcohol dependence. Methods In this study, we recruited 87 male patients with alcohol dependence from the alcohol center of one psychiatric hospital and 52 healthy male volunteers who were all employees in the same hospital as controls. We captured images of the right and left hands of patients and controls using a scanner and extracted data with a graphics program. We measured the 2D:4D of each hand and compared the alcohol dependence group with the control group. We analyzed these ratios using an independent-samples t-test. Results The mean 2D:4D of patients was 0.934 (right hand) and 0.942 (left hand), while the mean 2D:4D of controls was 0.956 (right hand) and 0.958 (left hand). Values for both hands were significantly lower for patients than controls (p<0.001, right hand; p=0.004, left hand). Conclusion Patients who are alcohol dependent have a significantly lower 2D:4D than controls, similar to the results of previous studies, which suggest that a higher prenatal testosterone level in the gonadal period is related to alcoholism. Furthermore, 2D:4D is a possible predictive marker of alcohol dependence. PMID:27121425

  2. European Code against Cancer 4th Edition: Environment, occupation and cancer.

    PubMed

    Espina, Carolina; Straif, Kurt; Friis, Søren; Kogevinas, Manolis; Saracci, Rodolfo; Vainio, Harri; Schüz, Joachim

    2015-12-01

    People are exposed throughout life to a wide range of environmental and occupational pollutants from different sources at home, in the workplace or in the general environment - exposures that normally cannot be directly controlled by the individual. Several chemicals, metals, dusts, fibres, and occupations have been established to be causally associated with an increased risk of specific cancers, such as cancers of the lung, skin and urinary bladder, and mesothelioma. Significant amounts of air pollutants - mainly from road transport and industry - continue to be emitted in the European Union (EU); an increased occurrence of lung cancer has been attributed to air pollution even in areas below the EU limits for daily air pollution. Additionally, a wide range of pesticides as well as industrial and household chemicals may lead to widespread human exposure, mainly through food and water. For most environmental pollutants, the most effective measures are regulations and community actions aimed at reducing and eliminating the exposures. Thus, it is imperative to raise awareness about environmental and occupational carcinogens in order to motivate individuals to be proactive in advocating protection and supporting initiatives aimed at reducing pollution. Regulations are not homogeneous across EU countries, and protective measures in the workplace are not used consistently by all workers all the time; compliance with regulations needs to be continuously monitored and enforced. Therefore, the recommendation on Environment and Occupation of the 4th edition of the European Code against Cancer, focusing on what individuals can do to reduce their cancer risk, reads: "In the workplace, protect yourself against cancer-causing substances by following health and safety instructions." PMID:26164655

  3. PREFACE: CYGNUS 2013: 4th Workshop on Directional Detection of Dark Matter

    NASA Astrophysics Data System (ADS)

    Naka, Tatsuhiro; Miuchi, Kentaro

    2013-12-01

    It is a great pleasure to publish the proceedings of the 4th Workshop on Directional Detection of Dark Matter held in Toyama, Japan on 10-12 June 2013 (CYGNUS 2013). These proceedings contain written versions of the presentations made at CYGNUS 2013 as scientific outputs of the directional detection of dark matter. The GYGNUS workshop started in 2007 at Boulby Underground Laboratory (UK), followed by CYGNUS 2009 (MIT in Cambridge, Massachusetts, USA) and CYGNUS 2011 (AUSSOIS, France). CYGNUS 2013 was held by the combination of a two and a half days of scientific program and a half day visit to the underground laboratory (Kamioka Observatory) as a 'tradition' of CYGNUS workshops. The name 'CYGNUS' came from the fact that the 'dark matter wind' is expected to come from the direction of the constellation Cygnus due to the motion of the Solar system in the galaxy. A general aim of these CYGNUS workshops is to bring together the theoretical and experimental studies on the directional dark matter detection. Directional detection of dark matter is a promising approach to a 'clear detection' and also to 'further investigations' of galactic dark matter, or Weakly Interacting Massive Particles (WIMPs). Directional detection requires the simultaneous detection of the energy and track of low energy recoils. Among many technological challenges for the requirement above, three of them, namely size, background, and directionality (angular resolution and head-tail detection), are most important to demonstrate and improve the quality as a dark matter detector. In the workshop, up-to-date activities by the international reserchers are discussed. The workshop was a great success thanks to the oral contributions and fruitful discussions held throughout the workshop period. We hope that readers will remember and share the great enthusiasm shown during the CYGNUS 2013 workshop. The Editors Tatsuhiro Naka and Kentaro Miuchi

  4. 4th International Conference on Energy and Environment 2013 (ICEE 2013)

    NASA Astrophysics Data System (ADS)

    Chakrabarty, Chandan Kumar; Shamsuddin, Abd Halim Bin; Ahmad, Ibrahim Bin; Desa, Mohamed Nor Bin Mohamed; Din, Norashidah Bte Md; Bte Mohd, Lariyah; Hamid, Nasri A.; See, Ong Hang; Hafiz Nagi, Farrukh; Yong, Lee Choon; Pasupuleti, Jagadeesh; Mei, Goh Su; Abdullah, Fairuz Bin; Satgunam, Meenaloshini

    2013-06-01

    The 4th International Conference on Energy & Environment 2013 (ICEE2013) was organized by the Universiti Tenaga Nasional (UNITEN) to provide a platform for creating and sharing ideas among engineers, researchers, scientists, industrialists and students in sustainable green energy and technologies. The theme 'Shaping a Sustainable Future through Advancement in Green Energy Technology' is in line with the University's vision to be a leading global energy university that shapes a sustainable future. The general scopes of the conference are renewable energy, smart grid, green technology, energy policies and economics, sustainable green energy and environment, sustainable education, international cooperation and innovation and technology transfer. Five international keynote speakers delivered their speeches in specialized areas of green energy technology and sustainability. In addition, the conference highlights several special parallel sessions by notable invited presenters in their niche areas, which are: Hybrid Energy Power Quality & Distributed Energy Smart Grid Nuclear Power & Technologies Geohazard Management Greener Environment for Sustainability Advances in Computational Fluid Dynamics The research papers presented in ICEE2013 are included in this volume of IOP Conference Series: Earth and Environmental Science (EES). EES is abstracted and indexed in SCOPUS, GeoBase, GeoRef, Compendex, Inspec, Chemical Abstracts Service, NASA Astrophysics Data System, and International Nuclear Information System (INIS). With the comprehensive programme outline, the organizing committee hopes that the ICEE2013 was a notable intellectual sharing session for the research and academic community in Malaysia and regionally. The organizing committee expresses gratitude to the ICEE2013 delegates for their great support and contributions to the event.

  5. Communicating Science to Impact Learning? A Phenomenological Inquiry into 4th and 5th Graders' Perceptions of Science Information Sources

    ERIC Educational Resources Information Center

    Gelmez Burakgazi, Sevinc; Yildirim, Ali; Weeth Feinstein, Noah

    2016-01-01

    Rooted in science education and science communication studies, this study examines 4th and 5th grade students' perceptions of science information sources (SIS) and their use in communicating science to students. It combines situated learning theory with uses and gratifications theory in a qualitative phenomenological analysis. Data were gathered…

  6. 75 FR 34374 - Safety Zone; Stockton Ports Baseball Club/City of Stockton, 4th of July Fireworks Display...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-17

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Stockton Ports Baseball Club/City of... Ports Baseball Club and the City of Stockton will sponsor the Stockton Ports Baseball Club/City of... Ports Baseball Club/City of Stockton 4th of July Fireworks Display, Stockton, CA. (a) Location....

  7. Impact of a Health and Media Literacy Curriculum on 4th-Grade Girls: A Qualitative Study

    ERIC Educational Resources Information Center

    Fuller, Heidi A.; Damico, Amy M.; Rodgers, Shannon

    2004-01-01

    Recent research indicates that young girls are preoccupied with their body size and that the media may be a contributing factor. This study aimed to discover the impact of an interdisciplinary media literacy intervention curriculum on 4th-grade girls in an urban elementary school. The authors developed and implemented a series of lessons that…

  8. Proceedings of the International Conference on Educational Data Mining (EDM) (4th, Eindhoven, the Netherlands, July 6-8, 2011)

    ERIC Educational Resources Information Center

    Pechenizkiy, Mykola; Calders, Toon; Conati, Cristina; Ventura, Sebastian; Romero, Cristobal; Stamper, John

    2011-01-01

    The 4th International Conference on Educational Data Mining (EDM 2011) brings together researchers from computer science, education, psychology, psychometrics, and statistics to analyze large datasets to answer educational research questions. The conference, held in Eindhoven, The Netherlands, July 6-9, 2011, follows the three previous editions…

  9. Assessment of Physical Activity Levels of 3rd and 4th Grade Children Using Pedometers during Physical Education Class

    ERIC Educational Resources Information Center

    Smith, John; Nichols, David; Biggerstaff, Kyle; DiMarco, Nancy

    2009-01-01

    The purpose of this study was to determine the amount of physical activity in which children engage during physical education classes and factors that mediate their participation. Third and 4th grade students wore pedometers during each 30-min physical education class for one school year. Steps per class were collected daily during structured and…

  10. Examining General and Specific Factors in the Dimensionality of Oral Language and Reading in 4th-10th Grades

    ERIC Educational Resources Information Center

    Foorman, Barbara R.; Koon, Sharon; Petscher, Yaacov; Mitchell, Alison; Truckenmiller, Adrea

    2015-01-01

    The objective of this study was to explore dimensions of oral language and reading and their influence on reading comprehension in a relatively understudied population--adolescent readers in 4th through 10th grades. The current study employed latent variable modeling of decoding fluency, vocabulary, syntax, and reading comprehension so as to…

  11. 75 FR 38723 - Safety Zone; St. Ignace 4th of July Fireworks, East Moran Bay, Lake Huron, St. Ignace, MI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-06

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; St. Ignace 4th of July Fireworks, East Moran Bay, Lake Huron, St. Ignace, MI AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast Guard is establishing a temporary safety zone on East Moran Bay, Lake Huron, St....

  12. 75 FR 34379 - Safety Zone; Mackinac Island 4th of July Fireworks, Lake Huron, Mackinac Island, MI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-17

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Mackinac Island 4th of July Fireworks, Lake Huron, Mackinac Island, MI AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast Guard is establishing a temporary safety zone on Lake Huron, Mackinac Island, Michigan. This zone...

  13. 77 FR 39422 - Eighth Coast Guard District Annual Safety Zones; Niceville July 4th Fireworks Show; Boggy Bayou...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-03

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Eighth Coast Guard District Annual Safety Zones; Niceville July 4th Fireworks Show; Boggy Bayou; Niceville, FL AGENCY: Coast Guard, DHS. ACTION: Notice of enforcement of regulation. SUMMARY: The Coast Guard will enforce a Safety Zone for the Niceville July...

  14. Comparing Science Learning among 4th-, 5th-, and 6th-Grade Students: STS versus Textbook-Based Instruction

    ERIC Educational Resources Information Center

    Yager, Robert E.; Choi, AeRan; Yager, Stuart O.; Akcay, Hakan

    2009-01-01

    Fifteen 4th-, 5th-, and 6th-grade teachers from five school districts each taught two sections of science--one with a Science-Technology-Society (STS) approach and the other with a more traditional textbook approach in which basic science concepts were the major organizers. Local, current, and personally relevant issues provided the context and…

  15. Native American Students' Understanding of Geologic Time Scale: 4th-8th Grade Ojibwe Students' Understanding of Earth's Geologic History

    ERIC Educational Resources Information Center

    Nam, Younkyeong; Karahan, Engin; Roehrig, Gillian

    2016-01-01

    Geologic time scale is a very important concept for understanding long-term earth system events such as climate change. This study examines forty-three 4th-8th grade Native American--particularly Ojibwe tribe--students' understanding of relative ordering and absolute time of Earth's significant geological and biological events. This study also…

  16. Using Inquiry-Based Instruction to Teach Research Methods to 4th-Grade Students in an Urban Setting

    ERIC Educational Resources Information Center

    Hamm, Ellen M.; Cullen, Rebecca; Ciaravino, Melissa

    2013-01-01

    When a college professor who teaches research methods to graduate education students was approached by a local public urban elementary school to help them teach research skills to 4th-graders, it was thought that the process would be simple--take what we did at the college level and differentiate it for the childhood classroom. This article will…

  17. 77 FR 39398 - Safety Zone and Special Local Regulation; 2012 Macy's 4th of July Fireworks and Spectator Viewing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-03

    ... enhance safety and improve the visual effect of the fireworks for the 2012 Macy's 4th of July Fireworks... Acronyms DHS Department of Homeland Security FR Federal Register NPRM Notice of Proposed Rulemaking COTP...'' in the Federal Register (76 FR 69613). In that rulemaking, the Coast Guard established a...

  18. The Influence of Neighborhood Density and Word Frequency on Phoneme Awareness in 2nd and 4th Grades

    ERIC Educational Resources Information Center

    Hogan, Tiffany P.; Bowles, Ryan P.; Catts, Hugh W.; Storkel, Holly L.

    2011-01-01

    Purpose: The purpose of this study was to test the hypothesis that two lexical characteristics--neighborhood density and word frequency--interact to influence performance on phoneme awareness tasks. Methods: Phoneme awareness was examined in a large, longitudinal dataset of 2nd and 4th grade children. Using linear logistic test model, the relation…

  19. Fluoroquinolone-based protocols for eradication of Helicobacter pylori

    PubMed Central

    Rispo, Antonio; Capone, Pietro; Castiglione, Fabiana; Pasquale, Luigi; Rea, Matilde; Caporaso, Nicola

    2014-01-01

    Helicobacter pylori (H. pylori) is a widespread pathogen infecting about 40% of people living in urban areas and over 90% of people living in the developing regions of the world. H. pylori is well-documented as the main factor in the pathogenesis of peptic ulcer disease, chronic gastritis, and gastric malignancies such as cancer and mucosa-associated lymphoid tissue-lymphoma; hence, its eradication is strongly recommended. The Maastricht IV consensus, which focused on the management of H. pylori infection, set important new strategies in terms of treatment approaches, particularly with regards to first- and second-line treatment protocols and led to improved knowledge and understanding of H. pylori resistance to antibiotics. In recent years, various fluoroquinolone-based protocols, mainly including levofloxacin, have been proposed and effectively tested at all therapeutic lines for H. pylori eradication. The aim of the present paper is to review the scientific literature focused on the use of fluoroquinolones in eradicating H. pylori. PMID:25083067

  20. Biofilm and fluoroquinolone resistance of canine Escherichia coli uropathogenic isolates

    PubMed Central

    2014-01-01

    Background Escherichia coli is the most common uropathogen involved in urinary tract infection (UTI). Virulence of strains may differ, and may be enhanced by antimicrobial resistance and biofilm formation, resulting in increased morbidity and recurrent infections. The aim of this study was to evaluate the in vitro biofilm forming capacity of E. coli isolates from dogs with UTI, by using fluorescent in situ hybridization, and its association with virulence genes and antimicrobial resistance. Findings The proportion of biofilm-producing isolates significantly increased with the length of incubation time (P < 0.05). Biofilm production was significantly associated with fluoroquinolone resistance at all incubation time points and was independent of the media used (P < 0.05). Biofilm production was not associated with cnf1, hly, pap and sfa genes (P > 0.05), but was significantly associated with afa, aer and the β-lactamase genes (P < 0.05). Conclusions To the best of our knowledge, this is the first report showing significant association between biofilm production and fluoroquinolone resistance in E. coli isolates from dogs with UTI. Biofilm formation may contribute to UTI treatment failure in dogs, through the development of bacterial reservoirs inside bladder cells, allowing them to overcome host immune defenses and to establish recurrent infections. PMID:25099929

  1. Designer antibacterial peptides kill fluoroquinolone-resistant clinical isolates.

    PubMed

    Otvos, Laszlo; Wade, John D; Lin, Feng; Condie, Barry A; Hanrieder, Joerg; Hoffmann, Ralf

    2005-08-11

    A significant number of Escherichia coli and Klebsiella pneumoniae bacterial strains in urinary tract infections are resistant to fluoroquinolones. Peptide antibiotics are viable alternatives although these are usually either toxic or insufficiently active. By applying multiple alignment and sequence optimization steps, we designed multifunctional proline-rich antibacterial peptides that maintained their DnaK-binding ability in bacteria and low toxicity in eukaryotes, but entered bacterial cells much more avidly than earlier peptide derivatives. The resulting chimeric and statistical analogues exhibited 8-32 microg/mL minimal inhibitory concentration efficacies in Muller-Hinton broth against a series of clinical pathogens. Significantly, the best peptide, compound 5, A3-APO, retained full antibacterial activity in the presence of mouse serum. Across a set of eight fluoroquinolone-resistant clinical isolates, peptide 5 was 4 times more potent than ciprofloxacin. On the basis of the in vitro efficacy, toxicity, and pharmacokinetics data, we estimate that peptide 5 will be suitable for treating infections in the 3-5 mg/kg dose range.

  2. Solubility, lipophilicity and membrane permeability of some fluoroquinolone antimicrobials.

    PubMed

    Blokhina, Svetlana V; Sharapova, Angelica V; Ol'khovich, Marina V; Volkova, Тatyana V; Perlovich, German L

    2016-10-10

    Aqueous solubility and distribution of ciprofloxacin, enrofloxacin, norfloxacin and levofloxacin antimicrobials drugs in octanol/buffer system has been measured by the isothermal saturation method using buffer solutions pH2.0 and 7.4 in the temperature range of 293.15-313.15K. Thermophysical characteristics for the compounds have been determined by the DSC method. It has been established that the solubility of levofloxacin in these buffers is higher than that of the other fluoroquinolones. HYBOT descriptors for biologically active compounds have been calculated and the impact of the donor-acceptor capacity of the molecules on drugs solubility has been studied. According to the lipophilicity parameter fluoroquinolones are ranged in the following order: enrofloxacin>levofloxacin>ciprofloxacin>norfloxacin. The thermodynamic solubility and distribution functions of the studied compounds have been obtained. The permeability coefficients of the substances through an artificial phospholipid membrane were determined. The drugs with a lower aqueous solubility were estimated to have higher distribution coefficients and membrane permeability. PMID:27473309

  3. PREFACE: 4th Global Conference on Materials Science and Engineering (CMSE 2015)

    NASA Astrophysics Data System (ADS)

    Ruda, H. E.; Khotsianovsky, A.

    2015-12-01

    IOP Conference Series: Materials Science and Engineering is publishing a volume of conference proceedings that contains a selection of papers presented at the 4th Global Conference on Materials Science and Engineering (CMSE 2015), which is an annual event that started in 2012. CMSE 2015, technically supported by the Institute of Applied Physics and Materials Engineering of University of Macau, organized by Wuhan Advance Materials Society, was successfully held at the University of Macau-new campus located on Hengqin Island from August 3rd-6th, 2015. It aims to bring together leading academic scientists, researchers and scholars to exchange and share their experience and research results on all aspects of Materials Science and Engineering, and to discuss the practical challenges encountered and the solutions adopted. Macau, one of the two special administrative regions of the People's Republic of China, where East meets West, turned out to be an ideal meeting place for domestic and overseas participants of this annual international conference. The conference program included keynote presentations, special sessions, oral and poster contributions. From several hundred submissions, 52 of the most promising and mainstream, IOP-relevant, contributions were included in this volume. The submissions present original ideas or results of general significance, supported by clear reasoning, compelling evidence and methods, theories and practices relevant to the research. The authors state clearly the problems and the significance of their research to theory and practice. Being a successful conference, this event gathered more than 200 qualified and high-level researchers and experts from over 40 countries, including 10 keynote speakers from 6 countries, which created a good platform for worldwide researchers and engineers to enjoy the academic communication. Taking advantage of this opportunity, we would like to thank all participants of this conference, and particularly the

  4. 4th Rare Disease South Eastern Europe (See) Meeting Skopje, Macedonia (November 14th, 2015).

    PubMed

    Gucev, Zoran; Tasic, Velibor; Polenakovic, Momir

    2015-01-01

    The 4th meeting on rare diseases in South Eastern Europe (SEE) was held in Skopje, at the Macedonian Academy of Sciences and Arts (MASA) on the 14(th) of November 2015. The focuses were metabolic, rare brain diseases as well as the rare dysmorphic syndrome. The authors of the report are particularly keen on stating that one of the main goals of the meeting, namely to help the treatment of patients with rare disease has begun to bear fruits. The talk on an iminosugar-based pharmacological chaperone compound as a drug candidate for the treatment of GM1-gangliosidosis and mucopolysaccharidosis IVB (Morquio disease type B) was enlightening. To date, there is no treatment available to be offered to patients, but chaperones lead mutated proteins to adopt a native-like conformation and to successfully traffic to their normal cellular destination. DORPHAN is developing an iminosugar-based pharmacological chaperone compound for the treatment of GM1-gangliosidosis and mucopolysaccharidosis IVB. A talk on recent developments in the laboratory diagnosis of mucopolysaccharidoses (MPS) was particularly interesting, covering the laboratory diagnosis of the MPS diseases by a strategy of clinical examination, biochemical analysis of urine samples, enzyme tests and genetic characterization of underlying mutations. New techniques were developed, including analysis of urinary glycosaminoglycans with tandem mass spectrometry, miniaturized enzyme tests or novel synthetic substrates for enzyme assays using mass spectrometry detection of products using dried blood spots. Feasibility and cost-effectiveness of these methods in newborn screening programs have been demonstrated. Neuromuscular RDs, and especially familial amyloid polyneuropathy (FAP) were a topic of the Bulgarian colleagues. Diagnosis, screening and the role of microglia were also topics of particular interest. In summary, this year RD meeting was exciting and productive on a wide range of diseases and on a novel insights on

  5. FOREWORD: 4th International Workshop on New Computational Methods for Inverse Problems (NCMIP2014)

    NASA Astrophysics Data System (ADS)

    2014-10-01

    This volume of Journal of Physics: Conference Series is dedicated to the scientific contributions presented during the 4th International Workshop on New Computational Methods for Inverse Problems, NCMIP 2014 (http://www.farman.ens-cachan.fr/NCMIP_2014.html). This workshop took place at Ecole Normale Supérieure de Cachan, on May 23, 2014. The prior editions of NCMIP also took place in Cachan, France, firstly within the scope of ValueTools Conference, in May 2011 (http://www.ncmip.org/2011/), and secondly at the initiative of Institut Farman, in May 2012 and May 2013, (http://www.farman.ens-cachan.fr/NCMIP_2012.html), (http://www.farman.ens-cachan.fr/NCMIP_2013.html). The New Computational Methods for Inverse Problems (NCMIP) Workshop focused on recent advances in the resolution of inverse problems. Indeed, inverse problems appear in numerous scientific areas such as geophysics, biological and medical imaging, material and structure characterization, electrical, mechanical and civil engineering, and finances. The resolution of inverse problems consists of estimating the parameters of the observed system or structure from data collected by an instrumental sensing or imaging device. Its success firstly requires the collection of relevant observation data. It also requires accurate models describing the physical interactions between the instrumental device and the observed system, as well as the intrinsic properties of the solution itself. Finally, it requires the design of robust, accurate and efficient inversion algorithms. Advanced sensor arrays and imaging devices provide high rate and high volume data; in this context, the efficient resolution of the inverse problem requires the joint development of new models and inversion methods, taking computational and implementation aspects into account. During this one-day workshop, researchers had the opportunity to bring to light and share new techniques and results in the field of inverse problems. The topics of the

  6. 4th Rare Disease South Eastern Europe (See) Meeting Skopje, Macedonia (November 14th, 2015).

    PubMed

    Gucev, Zoran; Tasic, Velibor; Polenakovic, Momir

    2015-01-01

    The 4th meeting on rare diseases in South Eastern Europe (SEE) was held in Skopje, at the Macedonian Academy of Sciences and Arts (MASA) on the 14(th) of November 2015. The focuses were metabolic, rare brain diseases as well as the rare dysmorphic syndrome. The authors of the report are particularly keen on stating that one of the main goals of the meeting, namely to help the treatment of patients with rare disease has begun to bear fruits. The talk on an iminosugar-based pharmacological chaperone compound as a drug candidate for the treatment of GM1-gangliosidosis and mucopolysaccharidosis IVB (Morquio disease type B) was enlightening. To date, there is no treatment available to be offered to patients, but chaperones lead mutated proteins to adopt a native-like conformation and to successfully traffic to their normal cellular destination. DORPHAN is developing an iminosugar-based pharmacological chaperone compound for the treatment of GM1-gangliosidosis and mucopolysaccharidosis IVB. A talk on recent developments in the laboratory diagnosis of mucopolysaccharidoses (MPS) was particularly interesting, covering the laboratory diagnosis of the MPS diseases by a strategy of clinical examination, biochemical analysis of urine samples, enzyme tests and genetic characterization of underlying mutations. New techniques were developed, including analysis of urinary glycosaminoglycans with tandem mass spectrometry, miniaturized enzyme tests or novel synthetic substrates for enzyme assays using mass spectrometry detection of products using dried blood spots. Feasibility and cost-effectiveness of these methods in newborn screening programs have been demonstrated. Neuromuscular RDs, and especially familial amyloid polyneuropathy (FAP) were a topic of the Bulgarian colleagues. Diagnosis, screening and the role of microglia were also topics of particular interest. In summary, this year RD meeting was exciting and productive on a wide range of diseases and on a novel insights on

  7. Fluoroquinolone susceptibility testing of Salmonella enterica: detection of acquired resistance and selection of zone diameter breakpoints for levofloxacin and ofloxacin.

    PubMed

    Sjölund-Karlsson, Maria; Howie, Rebecca L; Crump, John A; Whichard, Jean M

    2014-03-01

    Fluoroquinolones (e.g., ciprofloxacin) have become a mainstay for treating severe Salmonella infections in adults. Fluoroquinolone resistance in Salmonella is mostly due to mutations in the topoisomerase genes, but plasmid-mediated quinolone resistance (PMQR) mechanisms have also been described. In 2012, the Clinical and Laboratory Standards Institute (CLSI) revised the ciprofloxacin interpretive criteria (breakpoints) for disk diffusion and MIC test methods for Salmonella. In 2013, the CLSI published MIC breakpoints for Salmonella to levofloxacin and ofloxacin, but breakpoints for assigning disk diffusion results to susceptible (S), intermediate (I), and resistant (R) categories are still needed. In this study, the MICs and inhibition zone diameters for nalidixic acid, ciprofloxacin, levofloxacin, and ofloxacin were determined for 100 clinical isolates of nontyphi Salmonella with or without resistance mechanisms. We confirmed that the new levofloxacin MIC breakpoints resulted in the highest category agreement (94%) when plotted against the ciprofloxacin MICs and that the new ofloxacin MIC breakpoints resulted in 92% category agreement between ofloxacin and ciprofloxacin. By applying the new MIC breakpoints in the MIC zone scattergrams for levofloxacin and ofloxacin, the following disk diffusion breakpoints generated the least number of errors: ≥28 mm (S), 19 to 27 mm (I), and ≤18 mm (R) for levofloxacin and ≥25 mm (S), 16 to 24 mm (I), and ≤15 mm (R) for ofloxacin. Neither the levofloxacin nor the ofloxacin disk yielded good separation of isolates with and without resistance mechanisms. Further studies will be needed to develop a disk diffusion assay that efficiently detects all isolates with acquired resistance to fluoroquinolones.

  8. [Increase in antimicrobial resistance of Salmonella from food to fluoroquinolones and cephalosporins--a review of data from ten years].

    PubMed

    Tenhagen, Bernd-Alois; Schroeter, Andreas; Szabo, Istvan; Dorn, Christina; Appel, Bernd; Helmuth, Reiner; Käsbohrer, Annemarie

    2014-01-01

    Animal derived food is a relevant source of human infections with Salmonella enterica. In this paper we analyse the presence of Salmonella in meat with respect to the observed serovars and their resistance to the fluoroquinolone ciprofloxacin and 3rd generation cephalosporins in the years 2003 to 2012. Data originated from 8176 isolates that were isolated from meat, characterized in the National Reference Laboratory for Salmonella and tested for antimicrobial resistance in the National Reference Laboratory for antimicrobial resistance in this time period. The analysis reveals substantial differences in resistance patterns between isolates from different types of meat and different serovars. Frequent serovars were mostly associated with one type of meat, suggesting an additional influence of specific characteristics of the serovars besides the effect of selection pressure excerted by antimicrobial treatments. Results show a clear increase in resistance to fluoroquinolones and 3rd generation cephalosporins that was most prominent in isolates from poultry meat. Although the number of human infections with Salmonella in Germany decreased sharply in recent years, results indicate a substantial exposure of consumers to Salmonella that are resistant to important antimicrobials via meat.

  9. High prevalence of fluoroquinolone-nonsusceptible Streptococcus pyogenes emm12 in Taiwan.

    PubMed

    Lin, Jiun-Nong; Chang, Lin-Li; Lai, Chung-Hsu; Huang, Yi-Han; Chen, Wei-Fang; Yang, Chih-Hui; Hsu, Janine; Lin, Hsi-Hsun; Chen, Yen-Hsu

    2015-10-01

    Fluoroquinolone-nonsusceptible Streptococcus pyogenes has rapidly emerged in several countries. The aim of this study was to survey the epidemiology and molecular characteristics of fluoroquinolone-nonsusceptible S. pyogenes in Taiwan. A total of 350 consecutive S. pyogenes isolates were collected between January 2005 and December 2012, including 152 (43.4%) invasive and 198 (56.6%) noninvasive isolates. Thirty-nine isolates (11.1%) of S. pyogenes were nonsusceptible to fluoroquinolones, including one emm1/ST28, 4 emm4/ST39, 33 emm12/ST36, and 1 emm87/ST62. Of all the isolates, emm12 (50%) demonstrated the highest prevalence of fluoroquinolone nonsusceptibility. Alterations of Ser79Phe and Ala12Val in ParC were the most frequently mutations in fluoroquinolone-nonsusceptible S. pyogenes isolates. There were no amino acid substitutions in GyrB, and 1 emm87 isolate exhibited 3 nonsynonymous mutations in ParE. Our study reveals the emergence of fluoroquinolone-nonsusceptible S. pyogenes emm12/ST36 in Taiwan. Regular surveillance of fluoroquinolone susceptibility in S. pyogenes is suggested.

  10. Fluorescence characteristic study of the ternary complex of fluoroquinolone antibiotics and cobalt (II) with ATP

    NASA Astrophysics Data System (ADS)

    Wu, Shuqing; Zhang, Wujuan; Chen, Xingguo; Hu, Zhide; Hooper, Martin; Hooper, Beveley; Zhao, Zhengfeng

    2001-05-01

    The results from the measurement of the fluorescence spectra of fluoroquinolone antibiotics including ofloxacin (OF), norfloxacin (NOR) and ciprofloxacin (CIP) complexed with cobalt (II) and ATP give information concerning the antibiotics-nucleotide interactions. From the fluorescence spectral data, it appears that the fluoroquinolone antibiotic cannot directly complex with ATP but indirectly complex with cobalt (II), which is playing an intermediary role. The interaction of fluoroquinolone antibiotic with the nucleotide occurs mainly through the phosphate group. The conclusion offers a more complete mechanism, which is important for understanding the interaction of these drugs with DNA.

  11. PREFACE: The 4th Symposium on the Mechanics of Slender Structures (MoSS2013)

    NASA Astrophysics Data System (ADS)

    Cao, Dengqing; Kaczmarczyk, Stefan

    2013-07-01

    This volume of Journal of Physics: Conference Series contains papers presented at the 4th Symposium on the Mechanics of Slender Structures (MoSS2013) run under the auspices of the Institute of Physics Applied Mechanics Group and hosted by Harbin Institute of Technology (China) from 7-9 January 2013. The conference has been organized in collaboration with the Technical Committee on Vibration and Sound of the American Society of Mechanical Engineers and follows a one day seminar on Ropes, Cables, Belts and Chains: Theory and Applications and the MoSS2006 symposium held at the University of Northampton (UK) in 2004 and 2006, respectively, the MoSS2008 symposium held at the University of Maryland Baltimore County (USA) in 2008 and the MoSS2010 symposium hosted by Mondragon University and held in San Sebastian (Spain) in 2010. The remit of the Symposium on the Mechanics of Slender Structures series involves a broad range of scientific areas. Applications of slender structures include terrestrial, marine and space systems. Moving elastic elements such as ropes, cables, belts and tethers are pivotal components of many engineering systems. Their lengths often vary when the system is in operation. The applications include vertical transportation installations and, more recently, space tether propulsion systems. Traction drive elevator installations employ ropes and belts of variable length as a means of suspension, and also for the compensation of tensile forces over the traction sheave. In cranes and mine hoists, cables and ropes are subject to length variation in order to carry payloads. Tethers experiencing extension and retraction are important components of offshore and marine installations, as well as being proposed for a variety of different space vehicle propulsion systems based on different applications of momentum exchange and electrodynamic interactions with planetary magnetic fields. Furthermore, cables and slender rods are used extensively in civil engineering

  12. PREFACE: 4th Workshop on Theory, Modelling and Computational Methods for Semiconductors (TMCSIV)

    NASA Astrophysics Data System (ADS)

    Tomić, Stanko; Probert, Matt; Migliorato, Max; Pal, Joydeep

    2014-06-01

    These conference proceedings contain the written papers of the contributions presented at the 4th International Conference on Theory, Modelling and Computational Methods for Semiconductor materials and nanostructures. The conference was held at the MediaCityUK, University of Salford, Manchester, UK on 22-24 January 2014. The previous conferences in this series took place in 2012 at the University of Leeds, in 2010 at St William's College, York and in 2008 at the University of Manchester, UK. The development of high-performance computer architectures is finally allowing the routine use of accurate methods for calculating the structural, thermodynamic, vibrational, optical and electronic properties of semiconductors and their hetero- and nano-structures. The scope of this conference embraces modelling, theory and the use of sophisticated computational tools in semiconductor science and technology, where there is substantial potential for time-saving in R&D. Theoretical approaches represented in this meeting included: Density Functional Theory, Semi-empirical Electronic Structure Methods, Multi-scale Approaches, Modelling of PV devices, Electron Transport, and Graphene. Topics included, but were not limited to: Optical Properties of Quantum Nanostructures including Colloids and Nanotubes, Plasmonics, Magnetic Semiconductors, Photonic Structures, and Electronic Devices. This workshop ran for three days, with the objective of bringing together UK and international leading experts in the theoretical modelling of Group IV, III-V and II-VI semiconductors, as well as students, postdocs and early-career researchers. The first day focused on providing an introduction and overview of this vast field, aimed particularly at students, with several lectures given by recognized experts in various theoretical approaches. The following two days showcased some of the best theoretical research carried out in the UK in this field, with several contributions also from representatives of

  13. A review of psychosocial stress and chronic disease for 4th world indigenous peoples and African Americans.

    PubMed

    Paradies, Yin

    2006-01-01

    Public health literature indicates that psychosocial stress is an important contributor to chronic disease development. However, there is scant research on the health effects of stress for minority groups, who suffer from a high burden of chronic disease. This paper provides a review of studies that examine the relationship between psychosocial stress and chronic disease for 4th world indigenous groups and African Americans. A total of 50 associational and 15 intervention studies fit the inclusion criteria for this review. A range of chronic diseases, as well as harmful health behaviors, were associated with psychosocial stress for indigenous peoples and African Americans, with much stronger findings for mental rather than physical health outcomes. Several stress moderating factors were also identified and a small body of intervention research suggests that transcendental meditation and group-oriented stress management may be effective in reducing psychosocial stress and its effects for African Americans and 4th world indigenous groups respectively.

  14. R&W Club Frederick Hosts 4th Annual Golf Tournament Benefiting The Children’s Inn at NIH | Poster

    Cancer.gov

    The R&W Club Frederick’s 4th Annual Golf Tournament to benefit the Children’s Inn at NIH teed off on time despite cloudy weather and scattered showers. Employees from NCI at Frederick, the main NIH campus, and Leidos Biomed, along with family and friends, came to enjoy an afternoon at the beautiful Maryland National Golf Club in Middletown and to support a wonderful charity.

  15. Morphometrical analysis of the human suprarenal gland between the 4th and 7th months of gestation.

    PubMed

    Nowak, Dariusz; Góralczyk, Krzysztof; Zurada, Anna; Gielecki, Jerzy

    2007-01-01

    The present study's purpose has been to examine the development of the human suprarenal glands (SGs) during the prenatal period. Special attention was paid to sexual dimorphism and the differences between the parameters of the right and left SGs. Specimens were obtained from 187 human fetuses spontaneously aborted between the 4th and 7th months of gestation. The SGs were dissected from the fetuses after an immersion and preservation period of 3-24 months in 9% formalin solution. The mass and linear dimensions of each isolated SG were obtained, and these data revealed a progressive two-fold increase between the 4th and 7th months of gestation. There was a gradual reduction in the ratio of the SG mass to the overall mass of the fetus with a marked decrease evident between the 4th and 5th months. Statistical analysis of both SGs showed significant differences between sexes in the mass and in the thickness of the left SG during the 5th and 6th months of gestation. Differences in the mass and linear dimensions of the left and right SGs were recorded from the 5th month of gestation to the 7th month. The mass and volume of the left SGs were higher than those on the right side. This allometric analysis provides data from a large sample of human fetuses and will later aid in microscopic and ultrasonographic studies.

  16. Synthesis and biological evaluation of novel structural hybrids of benzofuroxan derivatives and fluoroquinolones.

    PubMed

    Chugunova, Elena; Akylbekov, Nurgali; Bulatova, Adelya; Gavrilov, Nikolai; Voloshina, Alexandra; Kulik, Natalia; Zobov, Vladimir; Dobrynin, Alexey; Syakaev, Victor; Burilov, Alexander

    2016-06-30

    A series of novel hybrids based on benzofuroxan derivatives and fluoroquinolones (4a-d-6a-d) have been synthesized. Unexpectedly, the reactions have resulted in salt products formation during the hydrolysis of benzofuroxans by water molecules being present in the solvent instead of usual substitution products. All the compounds have been screened for antimicrobial and toxic activities. All resulting compounds retain high activity characteristic for fluoroquinolones. Many of the salts based on benzofuroxans and fluoroquinolones have higher activity than starting fluoroquinolones against Bacillus cereus 8035. Among the screened compounds, the compound 4d has shown the best antibacterial activity against B. cereus 8035, 8 times higher than the original Lomefloxacin (MBC value 1.5 μg/mL). PMID:27061980

  17. Fluoroquinolone resistance does not impose a cost on the fitness of Clostridium difficile in vitro.

    PubMed

    Wasels, François; Kuehne, Sarah A; Cartman, Stephen T; Spigaglia, Patrizia; Barbanti, Fabrizio; Minton, Nigel P; Mastrantonio, Paola

    2015-03-01

    Point mutations conferring resistance to fluoroquinolones were introduced in the gyr genes of the reference strain Clostridium difficile 630. Only mutants with the substitution Thr-82→Ile in GyrA, which characterizes the hypervirulent epidemic clone III/027/NAP1, were resistant to all fluoroquinolones tested. The absence of a fitness cost in vitro for the most frequent mutations detected in resistant clinical isolates suggests that resistance will be maintained even in the absence of antibiotic pressure. PMID:25534738

  18. Molecular Characterization of Fluoroquinolone Resistance in Nontypeable Haemophilus influenzae Clinical Isolates

    PubMed Central

    Puig, Carmen; Tirado-Vélez, José Manuel; Calatayud, Laura; Tubau, Fe; Garmendia, Junkal; Ardanuy, Carmen; Marti, Sara

    2014-01-01

    Nontypeable Haemophilus influenzae (NTHi) is a common cause of respiratory infections in adults, who are frequently treated with fluoroquinolones. The aims of this study were to characterize the genotypes of fluoroquinolone-resistant NTHi isolates and their mechanisms of resistance. Among 7,267 H. influenzae isolates collected from adult patients from 2000 to 2013, 28 (0.39%) were ciprofloxacin resistant according to Clinical and Laboratory Standards Institute (CLSI) criteria. In addition, a nalidixic acid screening during 2010 to 2013 detected five (0.23%) isolates that were ciprofloxacin susceptible but nalidixic acid resistant. Sequencing of their quinolone resistance-determining regions and genotyping by pulse-field gel electrophoresis and multilocus sequence typing of the 25 ciprofloxacin-resistant isolates available and all 5 nalidixic acid-resistant isolates were performed. In the NTHi isolates studied, two mutations producing changes in two GyrA residues (Ser84, Asp88) and/or two ParC residues (Ser84, Glu88) were associated with increased fluoroquinolone MICs. Strains with one or two mutations (n = 15) had ciprofloxacin and levofloxacin MICs of 0.12 to 2 μg/ml, while those with three or more mutations (n = 15) had MICs of 4 to 16 μg/ml. Long persistence of fluoroquinolone-resistant strains was observed in three chronic obstructive pulmonary disease patients. High genetic diversity was observed among fluoroquinolone-resistant NTHi isolates. Although fluoroquinolones are commonly used to treat respiratory infections, the proportion of resistant NTHi isolates remains low. The nalidixic acid disk test is useful for detecting the first changes in GyrA or in GyrA plus ParC among fluoroquinolone-susceptible strains that are at a potential risk for the development of resistance under selective pressure by fluoroquinolone treatment. PMID:25385097

  19. Observational Cohort Study of Pregnancy Outcome after First-Trimester Exposure to Fluoroquinolones

    PubMed Central

    Wacker, Evelin; Meister, Reinhard; Panse, Mary; Weber-Schoendorfer, Corinna; Oppermann, Marc; Schaefer, Christof

    2014-01-01

    Fluoroquinolones are avoided during pregnancy due to developmental toxicity in animals. The aim of this study was to assess the fetal risk after intrauterine fluoroquinolone exposure. We performed an observational study of a prospectively ascertained cohort of pregnant women exposed to a fluoroquinolone during the first trimester. Pregnancy outcomes were compared to those of a cohort exposed to neither fluoroquinolones nor teratogenic or fetotoxic drugs. The outcomes evaluated were major birth defects (structural abnormalities of medical, surgical, or cosmetic relevance), spontaneous abortion, and elective termination of pregnancy. Pregnancy outcomes of 949 women with fluoroquinolone treatment were compared with those of 3,796 nonexposed controls. Neither the rate of major birth defects (2.4%; adjusted odds ratio [ORadj], 0.91; 95% confidence interval [CI], 0.6 to 1.5) nor the risk of spontaneous abortion (adjusted hazard ratio [HRadj], 1.01; 95% CI, 0.8 to 1.3) was increased. However, there was a nonsignificant increase in major birth defects after exposure to moxifloxacin (6/93, 6.5%; crude odds ratio [ORcrude], 2.40; 95% CI, 0.8 to 5.6). Neither a critical exposure time window within the first trimester nor a specific pattern of birth defects was demonstrated for any of the fluoroquinolones. The rate of electively terminated pregnancies was increased among the fluoroquinolone-exposed women (HRadj, 1.32; 95% CI, 1.03 to 1.7). The gestational ages at delivery and birth weights did not differ between groups. Our study did not detect an increased risk of spontaneous abortion or major birth defects. These reassuring findings support the recommendation to allow fluoroquinolone use in early pregnancy in selected cases. After the use of moxifloxacin, a detailed fetal ultrasound examination should be considered. PMID:24841264

  20. Quantitative comparison of the convulsive activity of combinations of twelve fluoroquinolones with five nonsteroidal antiinflammatory agents.

    PubMed

    Kim, Jahye; Ohtani, Hisakazu; Tsujimoto, Masayuki; Sawada, Yasufumi

    2009-01-01

    Concomitant administration of certain fluoroquinolone antimicrobials and nonsteroidal antiinflammatory agents (NSAIDs) induces serious convulsion in humans. There are differences in convulsive activity among fluoroquinolones and in the potentiation of fluoroquinolone-induced convulsion among NSAIDs, but a comprehensive, quantitative comparison has not been carried out. This study evaluates the inhibitory effects of twelve fluoroquinolones (ciprofloxacin, enoxacin, fleroxacin, gatifloxacin, levofloxacin, lomefloxacin, norfloxacin, ofloxacin, pazufloxacin, prulifloxacin, sparfloxacin, and tosufloxacin) alone or in the presence of an NSAID (4-biphenylacetic acid, diclofenac sodium, loxoprofen, lornoxicam or zaltoprofen) on the GABA(A) receptor binding of [(3)H]muscimol in an in vitro study using mice synaptic plasma membrane. The rank order of inhibitory effects of the fluoroquinolones was prulifloxacin asymptotically equal to norfloxacin > ciprofloxacin > or = enoxacin > gatifloxacin > or = ofloxacin asymptotically equal to tosufloxacin asymptotically equal to lomefloxacin > levofloxacin > or = sparfloxacin > or = pazufloxacin asymptotically equal to fleroxacin. 4-Biphenylacetic acid most potently enhanced the inhibitory effects of the fluoroquinolones, while zaltoprofen, loxoprofen, lornoxicam and diclofenac had essentially no effect. The clinical risk of convulsion for each combination was estimated using a pharmacodynamic model based on receptor occupancy using the in vitro data set obtained and pharmacokinetic parameters in humans collected from the literature. The combinations of 4-biphenylacetic acid with prulifloxacin and enoxacin were concluded to be the most hazardous.

  1. Something going on in Milan: a review of the 4th International PhD Student Cancer Conference

    PubMed Central

    Segré, C

    2010-01-01

    The 4th International PhD Student Cancer Conference was held at the IFOM-IEO-Campus in Milan from 19–21 May 2010 http://www.semm.it/events_researchPast.php The Conference covered many topics related to cancer, from basic biology to clinical aspects of the disease. All attendees presented their research, by either giving a talk or presenting a poster. This conference is an opportunity to introduce PhD students to top cancer research institutes across Europe. The core participanting institutes included: European School of Molecular Medicine (SEMM)—IFOM-IEO Campus, MilanBeatson Institute for Cancer Research (BICR), GlasgowCambridge Research Institute (CRI), Cambridge, UKMRC Gray Institute of Radiation Biology (GIROB), OxfordLondon Research Institute (LRI), LondonPaterson Institute for Cancer Research (PICR), ManchesterThe Netherlands Cancer Institute (NKI), Amsterdam ‘You organizers have crushed all my prejudices towards Italians. Congratulations, I enjoyed the conference immensely!’ Even if it might have sounded like rudeness for sure this was supposed to be a genuine compliment (at least, that’s how we took it), also considering that it was told by a guy who himself was the fusion of two usually antithetical concepts: fashion style and English nationality. The year 2010 has marked an important event for Italian research in the international scientific panorama: the European School of Molecular Medicine (SEMM) had the honour to host the 4th International PhD Student Cancer Conference, which was held from 19–21 May 2010 at the IFOM-IEO-Campus (http://www.semm.it/events_researchPast.php) in Milan. The conference was attended by more than one hundred students, coming from a selection of cutting edge European institutes devoted to cancer research. The rationale behind it is the promotion of cooperation among young scientists across Europe to debate about science and to exchange ideas and experiences. But that is not all, it is also designed for PhD students

  2. Something going on in Milan: a review of the 4th International PhD Student Cancer Conference.

    PubMed

    Segré, C

    2010-01-01

    The 4th International PhD Student Cancer Conference was held at the IFOM-IEO-Campus in Milan from 19-21 May 2010 http://www.semm.it/events_researchPast.phpThe Conference covered many topics related to cancer, from basic biology to clinical aspects of the disease. All attendees presented their research, by either giving a talk or presenting a poster. This conference is an opportunity to introduce PhD students to top cancer research institutes across Europe.THE CORE PARTICIPANTING INSTITUTES INCLUDED: European School of Molecular Medicine (SEMM)-IFOM-IEO Campus, MilanBeatson Institute for Cancer Research (BICR), GlasgowCambridge Research Institute (CRI), Cambridge, UKMRC Gray Institute of Radiation Biology (GIROB), OxfordLondon Research Institute (LRI), LondonPaterson Institute for Cancer Research (PICR), ManchesterThe Netherlands Cancer Institute (NKI), Amsterdam'You organizers have crushed all my prejudices towards Italians. Congratulations, I enjoyed the conference immensely!' Even if it might have sounded like rudeness for sure this was supposed to be a genuine compliment (at least, that's how we took it), also considering that it was told by a guy who himself was the fusion of two usually antithetical concepts: fashion style and English nationality.The year 2010 has marked an important event for Italian research in the international scientific panorama: the European School of Molecular Medicine (SEMM) had the honour to host the 4th International PhD Student Cancer Conference, which was held from 19-21 May 2010 at the IFOM-IEO-Campus (http://www.semm.it/events_researchPast.php) in Milan.The conference was attended by more than one hundred students, coming from a selection of cutting edge European institutes devoted to cancer research. The rationale behind it is the promotion of cooperation among young scientists across Europe to debate about science and to exchange ideas and experiences. But that is not all, it is also designed for PhD students to get in touch

  3. Induction of prophages by fluoroquinolones in Streptococcus pneumoniae: implications for emergence of resistance in genetically-related clones.

    PubMed

    López, Elena; Domenech, Arnau; Ferrándiz, María-José; Frias, Maria João; Ardanuy, Carmen; Ramirez, Mario; García, Ernesto; Liñares, Josefina; de la Campa, Adela G

    2014-01-01

    Antibiotic resistance in Streptococcus pneumoniae has increased worldwide by the spread of a few clones. Fluoroquinolone resistance occurs mainly by alteration of their intracellular targets, the type II DNA topoisomerases, which is acquired either by point mutation or by recombination. Increase in fluoroquinolone-resistance may depend on the balance between antibiotic consumption and the cost that resistance imposes to bacterial fitness. In addition, pneumococcal prophages could play an important role. Prophage induction by fluoroquinolones was confirmed in 4 clinical isolates by using Southern blot hybridization. Clinical isolates (105 fluoroquinolone-resistant and 160 fluoroquinolone-susceptible) were tested for lysogeny by using a PCR assay and functional prophage carriage was studied by mitomycin C induction. Fluoroquinolone-resistant strains harbored fewer inducible prophages (17/43) than fluoroquinolone-susceptible strains (49/70) (P = 0.0018). In addition, isolates of clones associated with fluoroquinolone resistance [CC156 (3/25); CC63 (2/20), and CC81 (1/19)], had lower frequency of functional prophages than isolates of clones with low incidence of fluoroquinolone resistance [CC30 (4/21), CC230 (5/20), CC62 (9/21), and CC180 (21/30)]. Likewise, persistent strains from patients with chronic respiratory diseases subjected to fluoroquinolone treatment had a low frequency of inducible prophages (1/11). Development of ciprofloxacin resistance was tested with two isogenic strains, one lysogenic and the other non-lysogenic: emergence of resistance was only observed in the non-lysogenic strain. These results are compatible with the lysis of lysogenic isolates receiving fluoroquinolones before the development of resistance and explain the inverse relation between presence of inducible prophages and fluoroquinolone-resistance. PMID:24718595

  4. Caldecott 4th bore tunnel project: influence of ground water flows and inflows triggered by tectonic fault zones?

    NASA Astrophysics Data System (ADS)

    Neuhuber, G.; G. Neuhuber1, W. Klary1, A. Nitschke1, B. Thapa2, Chris Risden3, T. Crampton4, D. Zerga5

    2011-12-01

    The 4th Bore is a highway tunnel on California State Route 24 currently under construction. The 4th Bore is undertaken by the California State Department of Transportation (CALTRANS) and the Contra Costa County Transportation Commission (CCTC) to alleviate traffic congestion on SR24 connecting the cities of Oakland and Orinda in the San Francisco East Bay Area. The cost for the 4th Bore is estimated at $ 390.8 Mill. The 3,249 ft long 4th Bore tunnel will have excavated dimensions of approximately 40 ft height and 49 ft width. A total of 7 cross passages will run between the 3rd and the new 4th bore. Geology and Hydrogeology: The project is located in the Oakland Berkeley Hills of the SF Bay Area. The Caldecott Tunnels lie within the easterly assemblage of the Hayward fault zone province which consists of a sequence of sedimentary and volcanic rocks that accumulated in the interval between about 16 and 8.4 Ma (Miocene). The basal rocks of these Tertiary deposits consist of deep marine basin sediments of the Monterey Group. These rocks are overlain uncomfortably by an interbedded sequence of terrestrial sediments (Orinda Formation) and volcanic rocks (Moraga Formation). The Tertiary rocks have been folded into large amplitude, NW trending folds that are cut by N trending strike and slip faults. The SF Bay Region, which is crossed by 4 major faults (San Gregorio, San Andreas, Hayward, and Calaveras), is considered one of the more seismically active regions of the world. The active Hayward fault lies 0.9mi to the west of the Caldecott Tunnels and is the closest major fault to the project area. The tunnel is at the moment under top heading construction: West Portal (360ft) and East Portal (1,968.5ft). While major faults typically influence groundwater flow, characterization of such influences is extremely difficult because of the heterogeneity of the hydraulic systems and the different lithological parameters and influences. Four major inactive fault zones striking

  5. 4th Quarter Transportation Report FY 2014: Radioactive Waste Shipments to and from the Nevada National Security Site (NNSS)

    SciTech Connect

    Gregory, Louis

    2014-12-02

    This report satisfies the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Field Office (NNSA/NFO) commitment to prepare a quarterly summary report of radioactive waste shipments to and from the Nevada National Security Site (NNSS) Radioactive Waste Management Complex (RWMC) at Area 5. There were no shipments sent for offsite treatment and returned to the NNSS this quarter. There was one shipment of two drums sent for offsite treatment and disposal. This report summarizes the 4th quarter of Fiscal Year (FY) 2014 low-level radioactive waste (LLW) and mixed low-level radioactive waste (MLLW) shipments. This report also includes annual summaries for FY 2014.

  6. Proceedings of the 4th Conference on Aerospace Materials, Processes, and Environmental Technology

    NASA Technical Reports Server (NTRS)

    Griffin, D. E. (Editor); Stanley, D. C. (Editor)

    2001-01-01

    The next millennium challenges us to produce innovative materials, processes, manufacturing, and environmental technologies that meet low-cost aerospace transportation needs while maintaining US leadership. The pursuit of advanced aerospace materials, manufacturing processes, and environmental technologies supports the development of safer, operational, next-generation, reusable, and expendable aeronautical and space vehicle systems. The Aerospace Materials, Processes, and Environmental Technology Conference (AMPET) provided a forum for manufacturing, environmental, materials, and processes engineers, scientists, and managers to describe, review, and critically assess advances in these key technology areas.

  7. Electrochemiluminescence of terbium (III)-two fluoroquinolones-sodium sulfite system in aqueous solution

    NASA Astrophysics Data System (ADS)

    Chen, Shi-lv; Ding, Fen; Liu, Yu; Zhao, Hui-chun

    2006-05-01

    The electrochemiluminescence (ECL) of Tb 3+-enoxacin-Na 2SO 3 system (ENX system) and Tb 3+-ofloxacin-Na 2SO 3 system (OFLX system) in aqueous solution is reported. ECL is generated by the oxidation of Na 2SO 3, which is enhanced by Tb 3+-fluoroquinolone (FQ) complex. The ECL intensity peak versus potential corresponds to oxidation of Na 2SO 3, and the ECL emission spectra (the peaks are at 490, 545, 585 and 620 nm) match the characteristic emission spectrum of Tb 3+, indicating that the emission is from the excited state of Tb 3+. The mechanism of ECL is proposed and the difference of ECL intensity between ENX system and OFLX system is explained. Conditions for ECL emission were optimized. The linear range of ECL intensity versus concentrations of pharmaceuticals is 2.0 × 10 -10-8.0 × 10 -7 mol l -1 for ENX and 6.0 × 10 -10-6.0 × 10 -7 mol l -1 for OFLX, respectively. A theoretical limit of detection is 5.4 × 10 -11 mol l -1 for ENX and 1.6 × 10 -10 mol l -1 for OFLX, respectively. The ECL was satisfactorily applied to the determination of the two FQs in dosage form and urine sample.

  8. Correlation of different phenotypic drug susceptibility testing methods for four fluoroquinolones in Mycobacterium tuberculosis

    PubMed Central

    Coeck, Nele; de Jong, Bouke C.; Diels, Maren; de Rijk, Pim; Ardizzoni, Elisa; Van Deun, Armand; Rigouts, Leen

    2016-01-01

    Background Molecular resistance testing fails to explain all fluoroquinolone resistance, with a continued need for a suitable rapid phenotypic drug susceptibility testing method. Objective To evaluate the optimal method for phenotypic fluoroquinolone susceptibility testing. Methods Using Löwenstein–Jensen medium, Middlebrook 7H11 agar, BACTEC-MGIT 960 and the resazurin microtitre plate assay, we determined susceptibility to fluoroquinolones in Mycobacterium tuberculosis and investigated cross-resistance between ofloxacin, levofloxacin, moxifloxacin and gatifloxacin. We compared MICs of all four fluoroquinolones for 91 strains on Löwenstein–Jensen (as the gold standard) with their MICs in resazurin plates, and with ofloxacin susceptibility at a single concentration in MGIT and on 7H11 agar, in addition to sequencing of the gyrAB genes. Results and conclusions Applying a cut-off of 2 mg/L ofloxacin, 1 mg/L levofloxacin and 0.5 mg/L moxifloxacin and gatifloxacin in all methods, some discordance between solid medium and MGIT methods was observed, yet this tended to be explained by MICs around the cut-off. The high discordance between Löwenstein–Jensen (LJ) and resazurin plates suggests that the currently applied cut-offs for all fluoroquinolones in the resazurin method should decrease and minor changes in colour (from blue to purple) be considered as meaningful. High-level resistance in all assays to all drugs correlated well with the presence of gyrA mutations, in support of recent findings that fluoroquinolone resistance should be tested at different concentrations, as patients with lower levels of resistance may continue to benefit from high-dose fluoroquinolone-based therapy. PMID:26851609

  9. Proceedings of the 4th Workshop of Young Researchers in Astronomy & Astrophysics

    NASA Astrophysics Data System (ADS)

    Forgács-Dajka, E.

    2006-09-01

    Preface: It is a great pleasure for the Organizers to present the proceedings already the Fourth Workshop of Young Researchers in Astronomy & Astrophysics. Six years ago the Organizers of the first meeting of these conference series declared that their intention is to begin a long-lasting tradition of such biennial conference series where the young postgraduate scientists can meet each other as well as with senior scholars on the wide fields of astronomy & astrophysics, and they can present their results, getting important experiences in presentation oral lectures. And, of course, vice versa this is a great possibility for the senior astronomers and astrophysicists to know the new generation, and form new connections.I am glad to say that the idea became successful. On the present, fourth meeting almost 50 lectures -- which covers many areas of astrophysics and related topics from solar physics to cosmology -- was presented by the young researchers affiliated to all those Hungarian scientific institutes, where astronomy and/or astrophysics are studied. It is a new and happily sequel, that a lot of hungarian young researchers who are working abroad came back to Hungary for a while to present their science. Like a bridge between the generation, a significant part of the lecturers are already not PhD students. They are mainly postdoctoral researchers who attended on the first conferences as young scientists, but feel theirself young in their hearts, and return back from meetings to meetings due to their nice memories. They are highly welcomed in the future, too. Furthermore, last, but not least I mention, that as a manifestation of the great honour of the senior generations to the young scientists several leading Hungarian experts of the different fields kindly accepted our invitation to present invited lectures on their research topics. The above mentiond topics of the present conference were as follows: Solar physics, Space Physics, Celestial Mechanics

  10. History of antibiotics: from fluoroquinolones to daptomycin (Part 2).

    PubMed

    Zaffiri, Lorenzo; Gardner, Jared; Toledo-Pereyra, Luis H

    2013-08-01

    In the Modern Era, physicians attested to the reciprocal influence among a technologically advanced society, rapid scientific progresses in medicine, and the need for new antimicrobials. The results of these changes were not only seen in the prolongation of life expectancy but also by the emergence of new pathogens. We first observed the advent of Gram-negative bacteria as a major source of nosocomial infections. The treatment of these microorganisms was complicated by the appearance and spread of drug resistance. We first focused on the development of two major classes of antimicrobials still currently used for the treatment of Gram-negative bacteria, such as fluoroquinolones and carbapenemes. Subsequently, we directed our attention to the growth of the incidence of infections due to Methicillin-Resistant Staphylococcus aureus (MRSA). Although the first MRSA was already isolated in 1961, the treatment of this new pathogen has been based on the efficacy of vancomycin for more than four decades. Only in the last 15 yr, we assisted in the development of new antimicrobial agents such as linezolid and daptomycin.

  11. Direct Optofluidic Measurement of the Lipid Permeability of Fluoroquinolones.

    PubMed

    Cama, Jehangir; Schaich, Michael; Al Nahas, Kareem; Hernández-Ainsa, Silvia; Pagliara, Stefano; Keyser, Ulrich F

    2016-01-01

    Quantifying drug permeability across lipid membranes is crucial for drug development. In addition, reduced membrane permeability is a leading cause of antibiotic resistance in bacteria, and hence there is a need for new technologies that can quantify antibiotic transport across biological membranes. We recently developed an optofluidic assay that directly determines the permeability coefficient of autofluorescent drug molecules across lipid membranes. Using ultraviolet fluorescence microscopy, we directly track drug accumulation in giant lipid vesicles as they traverse a microfluidic device while exposed to the drug. Importantly, our measurement does not require the knowledge of the octanol partition coefficient of the drug - we directly determine the permeability coefficient for the specific drug-lipid system. In this work, we report measurements on a range of fluoroquinolone antibiotics and find that their pH dependent lipid permeability can span over two orders of magnitude. We describe various technical improvements for our assay, and provide a new graphical user interface for data analysis to make the technology easier to use for the wider community.

  12. Fluoroquinolone Resistance in Penicillin-resistant Streptococcus pneumoniae Clones, Spain

    PubMed Central

    Balsalobre, Luz; Ardanuy, Carmen; Fenoll, Asunción; Pérez-Trallero, Emilio; Liñares, Josefina

    2004-01-01

    Among 2,882 Streptococcus pneumoniae sent to the Spanish Reference Laboratory during 2002, 75 (2.6%) were ciprofloxacin-resistant. Resistance was associated with older patients (3.9% in adults and 7.2% in patients >65 years of age), with isolation from noninvasive sites (4.3% vs. 1.0%), and with penicillin and macrolide resistance. Among 14 low-level resistant (MIC 4–8 µg/mL) strains, 1 had a fluoroquinolone efflux phenotype, and 13 showed single ParC changes. The 61 high-level ciprofloxacin-resistant (MIC >16 µg/mL) strains showed either two or three changes at ParC, ParE, and GyrA. Resistance was acquired either by point mutation (70 strains) or by recombination with viridans streptococci (4 strains) at the topoisomerase II genes. Although 36 pulsed-field gel electrophoresis patterns were observed, 5 international multiresistant clones (Spain23F-1, Spain6B-2, Spain9V-3, Spain14-5 and Sweden15A-25) accounted for 35 (46.7%) of the ciprofloxacin-resistant strains. Continuous surveillance is needed to prevent the dissemination of these clones. PMID:15504260

  13. Characterization of Recombinant Fluoroquinolone-Resistant Pneumococcus-Like Isolates

    PubMed Central

    Ortega, Montserrat; de la Campa, Adela G.

    2013-01-01

    Fourteen fluoroquinolone-resistant streptococcal isolates with recombinant DNA topoisomerase genes, preliminarily identified as pneumococci, were further characterized using phenotypic and genotypic approaches. Phenotypic tests classified them as atypical pneumococci. Phylogenetic relationships were analyzed by using the sequences of seven housekeeping alleles from these isolates and from isolates of Streptococcus pneumoniae, Streptococcus mitis, Streptococcus oralis, and Streptococcus pseudopneumoniae. Four isolates grouped with S. pneumoniae, seven grouped with S. pseudopneumoniae, and three grouped with S. mitis. These results generally agreed with those obtained with an optochin susceptibility test and with the organization of the atp operon chromosomal region, encoding the FoF1 H+-ATPase (the target of optochin). All seven isolates grouping with S. pseudopneumoniae share the same spr1368-atpC-atpA gene order; all four grouping with S. pneumoniae share the spr1368-IS1239-atpC-atpA order, and two out of the three grouping with S. mitis share the spr1284-atpC-atpA order. In addition, evidence for recombination within the seven housekeeping alleles of the S. pseudopneumoniae population was provided by several methods: the index of association (0.4598, P < 0.001), the pairwise homoplasy index, and the split-decomposition method. This study confirms the existence of pneumococci among the alpha-hemolytic streptococci with DNA topoisomerase genes showing a mosaic structure and reveals a close relationship between atypical pneumococci and S. pseudopneumoniae. PMID:23114769

  14. Direct Optofluidic Measurement of the Lipid Permeability of Fluoroquinolones

    PubMed Central

    Cama, Jehangir; Schaich, Michael; Al Nahas, Kareem; Hernández-Ainsa, Silvia; Pagliara, Stefano; Keyser, Ulrich F.

    2016-01-01

    Quantifying drug permeability across lipid membranes is crucial for drug development. In addition, reduced membrane permeability is a leading cause of antibiotic resistance in bacteria, and hence there is a need for new technologies that can quantify antibiotic transport across biological membranes. We recently developed an optofluidic assay that directly determines the permeability coefficient of autofluorescent drug molecules across lipid membranes. Using ultraviolet fluorescence microscopy, we directly track drug accumulation in giant lipid vesicles as they traverse a microfluidic device while exposed to the drug. Importantly, our measurement does not require the knowledge of the octanol partition coefficient of the drug – we directly determine the permeability coefficient for the specific drug-lipid system. In this work, we report measurements on a range of fluoroquinolone antibiotics and find that their pH dependent lipid permeability can span over two orders of magnitude. We describe various technical improvements for our assay, and provide a new graphical user interface for data analysis to make the technology easier to use for the wider community. PMID:27604156

  15. Direct Optofluidic Measurement of the Lipid Permeability of Fluoroquinolones.

    PubMed

    Cama, Jehangir; Schaich, Michael; Al Nahas, Kareem; Hernández-Ainsa, Silvia; Pagliara, Stefano; Keyser, Ulrich F

    2016-01-01

    Quantifying drug permeability across lipid membranes is crucial for drug development. In addition, reduced membrane permeability is a leading cause of antibiotic resistance in bacteria, and hence there is a need for new technologies that can quantify antibiotic transport across biological membranes. We recently developed an optofluidic assay that directly determines the permeability coefficient of autofluorescent drug molecules across lipid membranes. Using ultraviolet fluorescence microscopy, we directly track drug accumulation in giant lipid vesicles as they traverse a microfluidic device while exposed to the drug. Importantly, our measurement does not require the knowledge of the octanol partition coefficient of the drug - we directly determine the permeability coefficient for the specific drug-lipid system. In this work, we report measurements on a range of fluoroquinolone antibiotics and find that their pH dependent lipid permeability can span over two orders of magnitude. We describe various technical improvements for our assay, and provide a new graphical user interface for data analysis to make the technology easier to use for the wider community. PMID:27604156

  16. European Code against Cancer 4th Edition: Process of reviewing the scientific evidence and revising the recommendations.

    PubMed

    Minozzi, Silvia; Armaroli, Paola; Espina, Carolina; Villain, Patricia; Wiseman, Martin; Schüz, Joachim; Segnan, Nereo

    2015-12-01

    The European Code Against Cancer is a set of recommendations to give advice on cancer prevention. Its 4th edition is an update of the 3rd edition, from 2003. Working Groups of independent experts from different fields of cancer prevention were appointed to review the recommendations, supported by a Literature Group to provide scientific and technical support in the assessment of the scientific evidence, through systematic reviews of the literature. Common procedures were developed to guide the experts in identifying, retrieving, assessing, interpreting and summarizing the scientific evidence in order to revise the recommendations. The Code strictly followed the concept of providing advice to European Union citizens based on the current best available science. The advice, if followed, would be expected to reduce cancer risk, referring both to avoiding or reducing exposure to carcinogenic agents or changing behaviour related to cancer risk and to participating in medical interventions able to avert specific cancers or their consequences. The information sources and procedures for the review of the scientific evidence are described here in detail. The 12 recommendations of the 4th edition of the European Code Against Cancer were ultimately approved by a Scientific Committee of leading European cancer and public health experts.

  17. Effects of fluoroquinolone treatment and group housing of pigs on the selection and spread of fluoroquinolone-resistant Campylobacter.

    PubMed

    Usui, Masaru; Sakemi, Yoko; Uchida, Ikuo; Tamura, Yutaka

    2014-06-01

    There are concerns that the use of fluoroquinolones (FQs) and group housing of food animals may contribute to the development of bacterial FQ resistance. Here, we studied the effects of administering FQ to pigs on the selection of FQ-resistant Campylobacter. Fifteen pigs were randomly allocated to either a group treated with FQs (enrofloxacin or norfloxacin), or an untreated control group. The number of FQ-resistant Campylobacter in feces was determined using appropriate selective agar containing enrofloxacin. FQ-resistant Campylobacter from samples of both groups were observed on days 3 and 4. These bacteria persisted for up to 21 days after treatment was discontinued. To evaluate the effect of group housing on the transmission of FQ-resistant Campylobacter, five pigs infected with FQ-sensitive Campylobacter pigs and one pig infected with FQ-resistant Campylobacter were housed together. On day 3, FQ-resistant Campylobacter were isolated from all six pigs. Moreover, FQ-resistant Campylobacter were isolated from environmental samples from the pen. These results indicate that the treatment of pigs with FQs selects for and spreads FQ-resistant Campylobacter among the pen. Therefore, responsible and prudent use of FQs at pig farms is required to prevent the emergence and transmission of FQ-resistant Campylobacter.

  18. Inhibitory effect of several fluoroquinolones on hepatic microsomal cytochrome P-450 1A activities in dogs.

    PubMed

    Regmi, N L; Abd El-Aty, A M; Kuroha, M; Nakamura, M; Shimoda, M

    2005-12-01

    We examined inhibitory effects of ofloxacin (OFX), orbifloxacin (OBFX), ciprofloxacin (CFX), enrofloxacin (EFX) and norfloxacin (NFX) on cytochrome P-450 1A (CYP1A) activities using hepatic microsomes from four beagle dogs. Ethoxyresorufin O-de-ethylation was referred as CYP1A activities. All the fluoroquinolones inhibited the reaction in a noncompetitive manner. The determined inhibitory constants were the followings; 10.1 +/- 3.8 mM for OFX, 6.43 +/- 2.01 mM for OBFX, 0.726 +/- 0.134 mM for CFX, 4.06 +/- 1.19 mM for EFX and 4.75 +/- 1.63 mM for NFX respectively. As these values are >100-fold of plasma concentrations after a clinical single dose of the fluoroquinolones, it is suggested that the inhibitory effect on CYP1A activities is not so high to elicit drug-drug interaction with CYP1A substrates, when these fluoroquinolones are co-administered. Mechanism based inhibition was also examined in this study. Of the five fluoroquinolones examined, OFX, OBFX and CFX had this inhibition manner. As this inhibition is irreversible, inhibitory effects of the three fluoroquinolones may accumulate, when they are repeatedly administered. Therefore, OFX, OBFX and CFX may result in substantial drug-drug interaction with a CYP1A substrate even in clinical states. As EFX is metabolized to CFX in the body, it may also have the same possibility.

  19. PREFACE: 4th International Workshop & Summer School on Plasma Physics 2010

    NASA Astrophysics Data System (ADS)

    2014-06-01

    Fourth International Workshop & Summer School on Plasma Physics 2010 The Fourth International Workshop & Summer School on Plasma Physics (IWSSPP'10) is organized by St. Kliment Ohridsky University of Sofia, with co-organizers TCPA Foundation, Association EURATOM/IRNRE, The Union of the Physicists in Bulgaria, and the Bulgarian Academy of Sciences. It was held in Kiten, Bulgaria, at the Black Sea Coast, from July 5 to July 10, 2010. The scientific programme covers the topics Fusion Plasma and Materials; Plasma Modeling and Fundamentals; Plasma Sources, Diagnostics and Technology. As the previous issues of this scientific meeting (IWSSPP'05, J. Phys.: Conf. Series 44 (2006) and IWSSPP'06, J. Phys.: Conf. Series 63 (2007), IWSSPP'08, J. Phys.: Conf. Series 207 (2010), its aim was to stimulate the creation and support of a new generation of young scientists for further development of plasma physics fundamentals and applications, as well as to ensure an interdisciplinary exchange of views and initiate possible collaborations by bringing together scientists from various branches of plasma physics. This volume of Journal of Physics: Conference Series includes 34 papers (invited lectures, contributed talks and posters) devoted to various branches of plasma physics, among them fusion plasma and materials, dc and microwave discharge modelling, transport phenomena in gas discharge plasmas, plasma diagnostics, cross sections and rate constants of elementary processes, material processing, plasma-chemistry and technology. Some of them have been presented by internationally known and recognized specialists in their fields; others are MSc or PhD students' first steps in science. In both cases, we believe they will raise readers' interest. We would like to thank the members of both the International Advisory Committee and the Local Organizing Committee, the participants who sent their manuscripts and passed through the (sometimes heavy and troublesome) refereeing and editing

  20. Application of the FUN3D Unstructured-Grid Navier-Stokes Solver to the 4th AIAA Drag Prediction Workshop Cases

    NASA Technical Reports Server (NTRS)

    Lee-Rausch, Elizabeth M.; Hammond, Dana P.; Nielsen, Eric J.; Pirzadeh, S. Z.; Rumsey, Christopher L.

    2010-01-01

    FUN3D Navier-Stokes solutions were computed for the 4th AIAA Drag Prediction Workshop grid convergence study, downwash study, and Reynolds number study on a set of node-based mixed-element grids. All of the baseline tetrahedral grids were generated with the VGRID (developmental) advancing-layer and advancing-front grid generation software package following the gridding guidelines developed for the workshop. With maximum grid sizes exceeding 100 million nodes, the grid convergence study was particularly challenging for the node-based unstructured grid generators and flow solvers. At the time of the workshop, the super-fine grid with 105 million nodes and 600 million elements was the largest grid known to have been generated using VGRID. FUN3D Version 11.0 has a completely new pre- and post-processing paradigm that has been incorporated directly into the solver and functions entirely in a parallel, distributed memory environment. This feature allowed for practical pre-processing and solution times on the largest unstructured-grid size requested for the workshop. For the constant-lift grid convergence case, the convergence of total drag is approximately second-order on the finest three grids. The variation in total drag between the finest two grids is only 2 counts. At the finest grid levels, only small variations in wing and tail pressure distributions are seen with grid refinement. Similarly, a small wing side-of-body separation also shows little variation at the finest grid levels. Overall, the FUN3D results compare well with the structured-grid code CFL3D. The FUN3D downwash study and Reynolds number study results compare well with the range of results shown in the workshop presentations.

  1. An Ecological Study of Food Desert Prevalence and 4th Grade Academic Achievement in New York State School Districts

    PubMed Central

    Frndak, Seth E.

    2014-01-01

    Background This ecological study examines the relationship between food desert prevalence and academic achievement at the school district level. Design and methods Sample included 232 suburban and urban school districts in New York State. Multiple open-source databases were merged to obtain: 4th grade science, English and math scores, school district demographic composition (NYS Report Card), regional socioeconomic indicators (American Community Survey), school district quality (US Common Core of Data), and food desert data (USDA Food Desert Atlas). Multiple regression models assessed the percentage of variation in achievement scores explained by food desert variables, after controlling for additional predictors. Results The proportion of individuals living in food deserts significantly explained 4th grade achievement scores, after accounting for additional predictors. School districts with higher proportions of individuals living in food desert regions demonstrated lower 4th grade achievement across science, English and math. Conclusions Food deserts appear to be related to academic achievement at the school district level among urban and suburban regions. Further research is needed to better understand how food access is associated with academic achievement at the individual level. Significance for public health The prevalence of food deserts in the United States is of national concern. As poor nutrition in United States children continues to spark debate, food deserts are being evaluated as potential sources of low fruit and vegetable intake and high obesity rates. Cognitive development and IQ have been linked to nutrition patterns, suggesting that children in food desert regions may have a disadvantage academically. This research evaluates if an ecological relationship between food desert prevalence and academic achievement at the school district level can be demonstrated. Results suggest that food desert prevalence may relate to poor academic performance at

  2. Fluoroquinolone-metal complexes: a route to counteract bacterial resistance?

    PubMed

    Feio, Maria J; Sousa, Isabel; Ferreira, Mariana; Cunha-Silva, Luís; Saraiva, Raúl G; Queirós, Carla; Alexandre, José G; Claro, Vasco; Mendes, Adélia; Ortiz, Rosa; Lopes, Sandra; Amaral, Ana Luísa; Lino, João; Fernandes, Patrícia; Silva, Ana João; Moutinho, Lisete; de Castro, Baltazar; Pereira, Eulália; Perelló, Lourdes; Gameiro, Paula

    2014-09-01

    Microbial resistance to antibiotics is one of the biggest public health threats of the modern world. Antibiotic resistance is an area of much clinical relevance and therefore research that has the potential to identify agents that may circumvent it or treat resistant infections is paramount. Solution behavior of various fluoroquinolone (FQ) complexes with copper(II) in the presence and absence of 1,10-phenanthroline (phen) was studied in aqueous solution, by potentiometry and/or spectrophotometry, and are herein described. The results obtained showed that under physiological conditions (micromolar concentration range and pH7.4) only copper(II):FQ:phen ternary complexes are stable. Hence, these complexes were synthesised and characterised by means of UV-visible and IR spectroscopy, elemental analysis and single-crystal X-ray diffraction. In these complexes, the FQ acts as a bidentate ligand that coordinates the metal cation through the carbonyl and carboxyl oxygen atoms and phen coordinates through two N-atoms forming the equatorial plane of a distorted square-pyramidal geometry. The fifth position of the penta-coordinated Cu(II) centre is generally occupied axially by an oxygen atom from a water molecule or from a nitrate ion. Minimum inhibitory concentration (MIC) determinations of the complexes and comparison with free FQ in various E. coli strains indicate that the Cu-complexes are as efficient antimicrobials as the free antibiotic. Moreover, results strongly suggest that the cell intake route of both species is different supporting, therefore, the complexes' suitability as candidates for further biological testing in FQ-resistant microorganisms.

  3. Allogeneic hematopoietic cell transplantation without fluconazole and fluoroquinolone prophylaxis.

    PubMed

    Heidenreich, D; Kreil, S; Nolte, F; Reinwald, M; Hofmann, W-K; Klein, S A

    2016-01-01

    Fluoroquinolone (FQ) and fluconazole prophylaxis is recommended for patients undergoing allogeneic hematopoietic cell transplantation (alloHCT). However, due to an uncertain scientific basis and the increasing emergence of resistant germs, this policy should be questioned. Therefore, FQ and fluconazole prophylaxis was omitted in alloHCT at our center. In this retrospective analysis, all consecutive patients (n = 63) who underwent first alloHCT at our institution from September 2010 to September 2013 were included. Patients neither received FQ nor fluconazole prophylaxis. Day 100 mortality, incidence of febrile neutropenia, bacterial infections, and invasive fungal diseases (IFD) were assessed. Sixteen patients who started conditioning under antimicrobial treatment/prophylaxis due to pre-existing neutropenia (3/16), IFD (12/16), or aortic valve replacement (1/16) were excluded from the analysis. Finally, 47 patients were transplanted without prophylaxis as intended. Day 100 mortality was 9 %. Febrile neutropenia occurred in 62 % (29/47); 17/47 patients (36 %) experienced a blood stream infection (BSI) with detection of Gram-positive bacteria in 14 patients, Gram-negative bacteria in five patients, and candida in one patient, respectively. Coagulase-negative staphylococci were the most frequently isolated Gram-positive bacteria; 12/21 isolated Gram-positive and 3/6 Gram-negative bacteria were FQ resistant. In 21 % (10/47) of the patients, IFD (1x proven, 1x probable, and 8x possible) were diagnosed. To conclude, all three criteria, day 100 mortality, the incidence of IFD, and BSI, are in the range of published data for patients transplanted with FQ and fluconazole prophylaxis. These data demonstrate that alloHCT is feasible without FQ and fluconazole prophylaxis.

  4. Fluoroquinolone Resistance in Salmonella and the Utility of Pefloxacin Disk Diffusion [corrected].

    PubMed

    Fang, Ferric C

    2015-11-01

    Fluoroquinolone resistance is a serious and increasingly common problem in Salmonella. Two companion studies in this issue of the Journal of Clinical Microbiology (E. Deak, R. Skov, J. A. Hindler, and R. M. Humphries, J Clin Microbiol 53:3405-3410, 2015, http://dx.doi.org/10.1128/JCM.01393-15; R. Skov, E. Matuschek, M. Sjölund-Karlsson, J. Åhman, A. Petersen, M. Stegger, M. Torpdahl, and G. Kahlmeter, J Clin Microbiol 53:3411-3417, 2015, http://dx.doi.org/10.1128/JCM.01287-15) provide data to support the use of pefloxacin disk diffusion as a convenient and inexpensive surrogate laboratory method to detect fluoroquinolone resistance in Salmonella when the direct measurement of fluoroquinolone MICs is not feasible [corrected]. Recently updated CLSI and EUCAST susceptibility breakpoints will help to optimize clinical outcomes and reduce the likelihood of emergent resistance.

  5. Adjuvants Based on Hybrid Antibiotics Overcome Resistance in Pseudomonas aeruginosa and Enhance Fluoroquinolone Efficacy.

    PubMed

    Gorityala, Bala Kishan; Guchhait, Goutam; Fernando, Dinesh M; Deo, Soumya; McKenna, Sean A; Zhanel, George G; Kumar, Ayush; Schweizer, Frank

    2016-01-11

    The use of adjuvants that rescue antibiotics against multidrug-resistant (MDR) pathogens is a promising combination strategy for overcoming bacterial resistance. While the combination of β-lactam antibiotics and β-lactamase inhibitors has been successful in restoring antibacterial efficacy in MDR bacteria, the use of adjuvants to restore fluoroquinolone efficacy in MDR Gram-negative pathogens has been challenging. We describe tobramycin-ciprofloxacin hybrid adjuvants that rescue the activity of fluoroquinolone antibiotics against MDR and extremely drug-resistant Pseudomonas aeruginosa isolates in vitro and enhance fluoroquinolone efficacy in vivo. Structure-activity studies reveal that the presence of both tobramycin and ciprofloxacin, which are separated by a C12 tether, is critical for the function of the adjuvant. Mechanistic studies indicate that the antibacterial modes of ciprofloxacin are retained while the role of tobramycin is limited to destabilization of the outer membrane in the hybrid.

  6. Deoxynybomycins inhibit mutant DNA gyrase and rescue mice infected with fluoroquinolone-resistant bacteria

    PubMed Central

    Parkinson, Elizabeth I.; Bair, Joseph S.; Nakamura, Bradley A.; Lee, Hyang Y.; Kuttab, Hani I.; Southgate, Emma H.; Lezmi, Stéphane; Lau, Gee W.; Hergenrother, Paul J.

    2015-01-01

    Fluoroquinolones are one of the most commonly prescribed classes of antibiotics, but fluoroquinolone resistance (FQR) is widespread and increasing. Deoxynybomycin (DNM) is a natural-product antibiotic with an unusual mechanism of action, inhibiting the mutant DNA gyrase that confers FQR. Unfortunately, isolation of DNM is difficult and DNM is insoluble in aqueous solutions, making it a poor candidate for development. Here we describe a facile chemical route to produce DNM and its derivatives. These compounds possess excellent activity against FQR methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci clinical isolates and inhibit mutant DNA gyrase in-vitro. Bacteria that develop resistance to DNM are re-sensitized to fluoroquinolones, suggesting that resistance that emerges to DNM would be treatable. Using a DNM derivative, the first in-vivo efficacy of the nybomycin class is demonstrated in a mouse infection model. Overall, the data presented suggest the promise of DNM derivatives for the treatment of FQR infections. PMID:25907309

  7. Preliminary Study on LiF4-ThF4-PuF4 Utilization as Fuel Salt of miniFUJI Molten Salt Reactor

    NASA Astrophysics Data System (ADS)

    Waris, Abdul; Aji, Indarta K.; Pramuditya, Syeilendra; Widayani; Irwanto, Dwi

    2016-08-01

    miniFUJI reactor is molten salt reactor (MSR) which is one type of the Generation IV nuclear energy systems. The original miniFUJI reactor design uses LiF-BeF2-ThF4-233UF4 as a fuel salt. In the present study, the use of LiF4-ThF4-PuF4 as fuel salt instead of LiF-BeF2-ThF4-UF4 will be discussed. The neutronics cell calculation has been performed by using PIJ (collision probability method code) routine of SRAC 2006 code, with the nuclear data library is JENDL-4.0. The results reveal that the reactor can attain the criticality condition with the plutonium concentration in the fuel salt is equal to 9.16% or more. The conversion ratio diminishes with the enlarging of plutonium concentration in the fuel. The neutron spectrum of miniFUJI MSR with plutonium fuel becomes harder compared to that of the 233U fuel.

  8. Medical Standby: An Experience at the 4th National Youth Camping and Motivation Program Organized by Maksak Malaysia

    PubMed Central

    Zakaria, Mohd Idzwan; Isa, Ridzuan Mohd; Shah Che Hamzah, Mohd Shaharudin; Ayob, Noor Azleen

    2006-01-01

    Medical standby is the provision of emergency medical care and first aid for participants and/or spectators in a pre-planned event. This article describes the framework and the demographics of a medical standby at the 4th National Youth Camping and Motivation Program in Pasir Puteh, Kelantan from 30th July until the 3rd August 2004. The framework of the medical team is described based on the work process of any medical stand by. A medical encounter form was created for the medical standby defining the type of case seen (medical or trauma), name, age, race and diagnosis of the patient. We concluded that interagency collaboration during the initial planning and during the event itself is needed to ensure the smooth running of the medical standby. Most of the medical encounters were minor illnesses which are similar to previous studies and there was no case transferred to the hospital during that period. PMID:22589590

  9. 4th Annual Conference for African-American Researchers in the Mathematical Sciences (CAARMS4). Preliminary Program

    SciTech Connect

    Tapia, Richard

    1998-06-01

    In June, The Center for Research on Parallel Computation (CRPC), an NSF-funded Science and Technology Center, hosted the 4th Annual Conference for African-American Reserachers in the Mathematical Sciences (CAARMS4) at Rice University. The main goal of this conference was to highlight current work by African-American researchers and graduate students in mathematics. This conference strengthened the mathematical sciences by encouraging the increased participation of African-American and underrepresented groups into the field, facilitating working relationships between them and helping to cultivate their careers. In addition to the talks there was a graduate student poster session and tutorials on topics in mathematics and computer science. These talks, presentations, and discussions brought a broader perspective to the critical issues involving minority participation in mathematics.

  10. Neurobehavioral Evaluation System (NES): comparative performance of 2nd-, 4th-, and 8th-grade Czech children.

    PubMed

    Otto, D A; Skalik, I; House, D E; Hudnell, H K

    1996-01-01

    The Neurobehavioral Evaluation System was designed for field studies of workers, but many NES tests can be performed satisfactorily by children as young as 7 or 8 years old and a few tests, such as simple reaction time, can be performed by preschool children. However, little comparative data from children of different ages or grade levels are available. Studies of school children in the Czech Republic indicate that 2nd-grade children could perform the following NES tests satisfactorily: Finger Tapping, Visual Digit Span. Continuous Performance, Symbol-Digit Substitution, Pattern Comparison, and simpler conditions of Switching Attention. Comparative scores of boys and girls from the 2nd, 4th, and 8th grades and power analyses to estimate appropriate sample size were presented. Performance varied systematically with grade level and gender. Larger samples were needed with younger children to achieve comparable levels of statistical power. Gender comparisons indicated that boys responded faster, but made more errors than girls. PMID:8866533

  11. Medical Standby: An Experience at the 4(th) National Youth Camping and Motivation Program Organized by Maksak Malaysia.

    PubMed

    Zakaria, Mohd Idzwan; Isa, Ridzuan Mohd; Shah Che Hamzah, Mohd Shaharudin; Ayob, Noor Azleen

    2006-01-01

    Medical standby is the provision of emergency medical care and first aid for participants and/or spectators in a pre-planned event. This article describes the framework and the demographics of a medical standby at the 4(th) National Youth Camping and Motivation Program in Pasir Puteh, Kelantan from 30(th) July until the 3(rd) August 2004. The framework of the medical team is described based on the work process of any medical stand by. A medical encounter form was created for the medical standby defining the type of case seen (medical or trauma), name, age, race and diagnosis of the patient. We concluded that interagency collaboration during the initial planning and during the event itself is needed to ensure the smooth running of the medical standby. Most of the medical encounters were minor illnesses which are similar to previous studies and there was no case transferred to the hospital during that period. PMID:22589590

  12. Macracanthorhynchus hirudinaceus Eggs in Canine Coprolite from the Sasanian Era in Iran (4th/5th Century CE)

    PubMed Central

    MOWLAVI, Gholamreza; MAKKI, Mahsasadat; HEIDARI, Zahra; REZAEIAN, Mostafa; MOHEBALI, Mehdi; ARAUJO, Adauto; BOENKE, Nicole; AALI, Abolfazl; STOLLNER, Thomas; MOBEDI, Iraj

    2015-01-01

    Present paper is the second publication introducing the paleoparasitological findings from animal coprolites obtained from archeological site of Chehrabad salt mine in northwestern Iran. The current archeological site is located in northwest of Iran, dated to the Sassanian Era (4th/5th century CE). In the summer 2012 the carnivore coprolite was obtained within the layers in the mine and were thoroughly analyzed for parasites using TSP rehydration technique. Eggs of 0 were successfully retrieved from the examined coprolite and were confidently identified based on reliable references. Identifying of M. hirudinaceus eggs in paleofeces with clear appearance as demonstrated herein, is much due to appropriate preservation condition has been existed in the salt mine .The present finding could be regarded as the oldest acanthocephalan infection in Iran. PMID:26246822

  13. Top 10 Dietary Supplements of Korean Adults from the 4th Korea National Health and Nutrition Examination Survey

    PubMed Central

    2011-01-01

    The aim of this study is to assess the prevalence, types, and trends of dietary supplement (DS) use. We analyzed the Dietary Supplement Questionnaire data of Korean aged 19 years old or older from the Nutrition Survey of the 4th Korea National Health and Nutrition Survey. Each reported DS was coded based on ingredients according to the 2010 Korean Food and Drug Administration Notification. The prevalence (standard error) of current DS use was 20.6% (0.7) for men, 32.2% (0.7) for women. Those with DS use for longer than two weeks during previous one year were 27.2% (0.7), and 40.2% (0.8), for men and women respectively. Vitamin mineral supplement (221.6/103 persons) was the most frequently consumed DS in Korean adults. The trend for DS use in Korean adults is changing as well as increasing. PMID:22745863

  14. Detection of Helicobacter pylori resistance to clarithromycin and fluoroquinolones in Brazil: A national survey

    PubMed Central

    Sanches, Bruno Squarcio; Martins, Gustavo Miranda; Lima, Karine; Cota, Bianca; Moretzsohn, Luciana Dias; Ribeiro, Laercio Tenorio; Breyer, Helenice P; Maguilnik, Ismael; Maia, Aline Bessa; Rezende-Filho, Joffre; Meira, Ana Carolina; Pinto, Henrique; Alves, Edson; Mascarenhas, Ramiro; Passos, Raissa; de Souza, Julia Duarte; Trindade, Osmar Reni; Coelho, Luiz Gonzaga

    2016-01-01

    AIM To evaluate bacterial resistance to clarithromycin and fluoroquinolones in Brazil using molecular methods. METHODS The primary antibiotic resistance rates of Helicobacter pylori (H. pylori) were determined from November 2012 to March 2015 in the Southern, South-Eastern, Northern, North-Eastern, and Central-Western regions of Brazil. Four hundred ninety H. pylori patients [66% female, mean age 43 years (range: 18-79)] who had never been previously treated for this infection were enrolled. All patients underwent gastroscopy with antrum and corpus biopsies and molecular testing using GenoType HelicoDR (Hain Life Science, Germany). This test was performed to detect the presence of H. pylori and to identify point mutations in the genes responsible for clarithromycin and fluoroquinolone resistance. The molecular procedure was divided into three steps: DNA extraction from the biopsies, multiplex amplification, and reverse hybridization. RESULTS Clarithromycin resistance was found in 83 (16.9%) patients, and fluoroquinolone resistance was found in 66 (13.5%) patients. There was no statistical difference in resistance to either clarithromycin or fluoroquinolones (P = 0.55 and P = 0.06, respectively) among the different regions of Brazil. Dual resistance to clarithromycin and fluoroquinolones was found in 4.3% (21/490) of patients. The A2147G mutation was present in 90.4% (75/83), A2146G in 16.9% (14/83) and A2146C in 3.6% (3/83) of clarithromycin-resistant patients. In 10.8% (9/83) of clarithromycin-resistant samples, more than 01 mutation in the 23S rRNA gene was noticed. In fluoroquinolone-resistant samples, 37.9% (25/66) showed mutations not specified by the GenoType HelicoDR test. D91N mutation was observed in 34.8% (23/66), D91G in 18.1% (12/66), N87K in 16.6% (11/66) and D91Y in 13.6% (9/66) of cases. Among fluoroquinolone-resistant samples, 37.9% (25/66) showed mutations not specified by the GenoType HelicoDR test. CONCLUSION The H. pylori clarithromycin

  15. Detection of Helicobacter pylori resistance to clarithromycin and fluoroquinolones in Brazil: A national survey

    PubMed Central

    Sanches, Bruno Squarcio; Martins, Gustavo Miranda; Lima, Karine; Cota, Bianca; Moretzsohn, Luciana Dias; Ribeiro, Laercio Tenorio; Breyer, Helenice P; Maguilnik, Ismael; Maia, Aline Bessa; Rezende-Filho, Joffre; Meira, Ana Carolina; Pinto, Henrique; Alves, Edson; Mascarenhas, Ramiro; Passos, Raissa; de Souza, Julia Duarte; Trindade, Osmar Reni; Coelho, Luiz Gonzaga

    2016-01-01

    AIM To evaluate bacterial resistance to clarithromycin and fluoroquinolones in Brazil using molecular methods. METHODS The primary antibiotic resistance rates of Helicobacter pylori (H. pylori) were determined from November 2012 to March 2015 in the Southern, South-Eastern, Northern, North-Eastern, and Central-Western regions of Brazil. Four hundred ninety H. pylori patients [66% female, mean age 43 years (range: 18-79)] who had never been previously treated for this infection were enrolled. All patients underwent gastroscopy with antrum and corpus biopsies and molecular testing using GenoType HelicoDR (Hain Life Science, Germany). This test was performed to detect the presence of H. pylori and to identify point mutations in the genes responsible for clarithromycin and fluoroquinolone resistance. The molecular procedure was divided into three steps: DNA extraction from the biopsies, multiplex amplification, and reverse hybridization. RESULTS Clarithromycin resistance was found in 83 (16.9%) patients, and fluoroquinolone resistance was found in 66 (13.5%) patients. There was no statistical difference in resistance to either clarithromycin or fluoroquinolones (P = 0.55 and P = 0.06, respectively) among the different regions of Brazil. Dual resistance to clarithromycin and fluoroquinolones was found in 4.3% (21/490) of patients. The A2147G mutation was present in 90.4% (75/83), A2146G in 16.9% (14/83) and A2146C in 3.6% (3/83) of clarithromycin-resistant patients. In 10.8% (9/83) of clarithromycin-resistant samples, more than 01 mutation in the 23S rRNA gene was noticed. In fluoroquinolone-resistant samples, 37.9% (25/66) showed mutations not specified by the GenoType HelicoDR test. D91N mutation was observed in 34.8% (23/66), D91G in 18.1% (12/66), N87K in 16.6% (11/66) and D91Y in 13.6% (9/66) of cases. Among fluoroquinolone-resistant samples, 37.9% (25/66) showed mutations not specified by the GenoType HelicoDR test. CONCLUSION The H. pylori clarithromycin

  16. Occurrence of (fluoro)quinolones and (fluoro)quinolone resistance in soil receiving swine manure for 11 years.

    PubMed

    Xu, Yonggang; Yu, Wantai; Ma, Qiang; Zhou, Hua

    2015-10-15

    Because of the widespread use of antibiotics in animal breeding, the agricultural application of animal manure can lead to the introduction of antibiotics, antibiotic-resistant bacteria and antibiotic resistance genes to the soil and surrounding environment, which may pose a threat to public health. In this study, we investigated the status of (fluoro)quinolone (FQ) residues and FQ resistance levels in soil with and without receiving long-term swine manure. Six FQs (pipemidic acid, lomefloxacin, enrofloxacin, norfloxacin, ciprofloxacin, and ofloxacin) were only detected in manured soil, with individual concentrations ranging from below the detection limit to 27.2 μg kg(-1) and increasing with the increase in swine manure application rates. Higher load rates of swine manure yielded a higher number of ciprofloxacin-resistant (CIPr) bacteria after spreading. A total of 24 CIPr bacterial isolates were obtained from the tested soil, which belonged to four phyla (Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes) or were related to nine different genera. Only 18 isolates from manured soil were positive for five plasmid-mediated quinolone resistance (PMQR) genes (aac(6')-Ib-cr, qnrD, qepA, oqxA, and oqxB). To our knowledge, this study is the first to examine the occurrence of PMQR genes in FQ-resistant bacteria from the soil environment. A similar result was observed for the total DNA from soil, with the exception of aac(6')-Ib being detected in the control sample. The absolute and relative abundances of total PMQR genes also increased with fertilization quantity. Significant correlations were observed between FQ resistance levels and FQ concentrations. These results indicated that the agricultural application of swine manure led to FQ residues and enhanced FQ resistance. This investigation provides baseline data on FQ resistance profiles in soils receiving long-term swine manure.

  17. Overcoming CD4 Th1 Cell Fate Restrictions to Sustain Antiviral CD8 T Cells and Control Persistent Virus Infection.

    PubMed

    Snell, Laura M; Osokine, Ivan; Yamada, Douglas H; De la Fuente, Justin Rafael; Elsaesser, Heidi J; Brooks, David G

    2016-09-20

    Viral persistence specifically inhibits CD4 Th1 responses and promotes Tfh immunity, but the mechanisms that suppress Th1 cells and the disease consequences of their loss are unclear. Here, we demonstrate that the loss of CD4 Th1 cells specifically leads to progressive CD8 T cell decline and dysfunction during viral persistence. Therapeutically reconstituting CD4 Th1 cells restored CD4 T cell polyfunctionality, enhanced antiviral CD8 T cell numbers and function, and enabled viral control. Mechanistically, combined interaction of PD-L1 and IL-10 by suppressive dendritic cell subsets inhibited new CD4 Th1 cells in both acute and persistent virus infection, demonstrating an unrecognized suppressive function for PD-L1 in virus infection. Thus, the loss of CD4 Th1 cells is a key event leading to progressive CD8 T cell demise during viral persistence with important implications for restoring antiviral CD8 T cell immunity to control persistent viral infection.

  18. Overcoming CD4 Th1 Cell Fate Restrictions to Sustain Antiviral CD8 T Cells and Control Persistent Virus Infection.

    PubMed

    Snell, Laura M; Osokine, Ivan; Yamada, Douglas H; De la Fuente, Justin Rafael; Elsaesser, Heidi J; Brooks, David G

    2016-09-20

    Viral persistence specifically inhibits CD4 Th1 responses and promotes Tfh immunity, but the mechanisms that suppress Th1 cells and the disease consequences of their loss are unclear. Here, we demonstrate that the loss of CD4 Th1 cells specifically leads to progressive CD8 T cell decline and dysfunction during viral persistence. Therapeutically reconstituting CD4 Th1 cells restored CD4 T cell polyfunctionality, enhanced antiviral CD8 T cell numbers and function, and enabled viral control. Mechanistically, combined interaction of PD-L1 and IL-10 by suppressive dendritic cell subsets inhibited new CD4 Th1 cells in both acute and persistent virus infection, demonstrating an unrecognized suppressive function for PD-L1 in virus infection. Thus, the loss of CD4 Th1 cells is a key event leading to progressive CD8 T cell demise during viral persistence with important implications for restoring antiviral CD8 T cell immunity to control persistent viral infection. PMID:27653690

  19. Fluorescence quenching of fluoroquinolone antibiotics by 4-hydroxy-TEMPO in aqueous solution.

    PubMed

    Żamojć, Krzysztof; Wiczk, Wiesław; Zaborowski, Bartłomiej; Makowski, Mariusz; Pranczk, Joanna; Jacewicz, Dagmara; Chmurzyński, Lech

    2014-12-10

    The fluorescence quenching of norfloxacin, danofloxacin, enrofloxacin and levofloxacin, belonging to a group of fluoroquinolone antibiotics, by 4-hydroxy-TEMPO was studied in aqueous solutions with the use of steady-state, time-resolved fluorescence spectroscopy as well as UV-VIS absorption spectroscopy methods. In order to understand the mechanism of quenching the absorption and fluorescence emission spectra of all fluoroquinolone antibiotics studied as well as decreases of their fluorescence were registered as a function of the 4-hydroxy-TEMPO concentration. No deviations from a linearity in the Stern-Volmer plots (determined from both, steady-state and time-resolved measurements) were observed. The fluorescence quenching mechanism was proved to be totally dynamic, what was additionally confirmed by the registration of Stern-Volmer plots at 5 temperatures ranging from 15 to 55°C. On the basis of theoretical calculations of fluoroquinolones' molecular radii and ionization potentials the mechanism of electron transfer was rejected. It seems that the fluorescence quenching is diffusion-limited and is caused by the increase of nonradiative processes, such as internal conversion or intersystem crossing. The Stern-Volmer quenching constants and bimolecular quenching constants were determined at the room temperature for all fluoroquinolone antibiotics studied.

  20. Biological cost of fluoroquinolone resistance in Escherichia coli implicated in polyclonal infection.

    PubMed

    Bémer, P; Corvec, S; Guitton, C; Giraudeau, C; Le Gargasson, G; Espaze, E; Drugeon, H

    2007-07-01

    Polyclonal Escherichia coli strains were isolated in a transplanted patient who experienced successive septic shocks. Fluoroquinolone susceptible and resistant strains were corresponding to different PFGE fragment profiles. The gyrA S83L mutation was associated with a reduction in biological fitness. Resistant strain was selected by a long-term single use of ofloxacin.

  1. Fluoroquinolone induction of phage-mediated gene transfer in multidrug-resistant Salmonella

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fluoroquinolones are broad spectrum antibiotics that inhibit bacterial DNA gyrase and topoisomerase activity, which can cause damage DNA and result in bacterial cell death. In response to DNA damage, bacteria induce an SOS response to stimulate repair of damaged DNA. However, the SOS response may al...

  2. [Synthesis and anti-proliferative activity of fluoroquinolone (rhodanine unsaturated ketone) amide derivatives].

    PubMed

    Gao, Liu-zhou; Xie, Yu-suo; Yan, Qiang; Wu, Shu-min; Ni, Li-li; Zhao, Hui; Huang, Wen-long; Hu, Guo-qiang

    2015-08-01

    To discover novel antitumor rhodanine unsaturated ketones, a series of fluoroquinolone (rhodanine α, β-unsaturated ketone) amine derivatives (5a-5r) were designed and synthesized with fluoroquinolone amide scaffold as a carrier. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS. The in vitro anti-proliferative activity against Hep-3B, Capan-1 and HL60 cells was evaluated by MTT assay. The results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. The SAR revealed that some compounds carrying aromatic heterocyclic rings or phenyl attached to an electron-withdrawing carboxyl or sulfonamide substituent were comparable to or better than comparison doxorubicin against Capan-1 cells. As such, it suggests that fluoroquinolone (rhodanine α, β-unsaturated ketone) amines are promising leads for the development of novel antitumor fluoroquinolones or rhodanine analogues. PMID:26669001

  3. Screening of fluoroquinolone residues in caprine milk using a 5-kg luminescence photometer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A terbium-sensitized luminescence (TSL) method was developed to screen presence of residues of four fluoroquinolones (FQ) registered in caprine milk in the European Union: enrofloxacin, ciprofloxacin, flumequine, and danofloxacin. After extraction in McIlvaine buffer and SPE cleanup, TSL was measure...

  4. Design of a portable fluoroquinolone analyzer based on terbium-sensitized luminescence

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A portable fluoroquinolone (FQ) analyzer is developed in this laboratory based on terbium-sensitized luminescence (TSL). The optical, hardware and software design aspects are described in detail. A 327-nm light emitting diode (LED) is used in pulsed mode as the excitation source; and a photomultip...

  5. Wildlife contamination with fluoroquinolones from livestock: Widespread occurrence of enrofloxacin and marbofloxacin in vultures.

    PubMed

    Blanco, Guillermo; Junza, Alexandra; Segarra, David; Barbosa, José; Barrón, Dolores

    2016-02-01

    There is much recent interest in the presence and impact of veterinary pharmaceuticals in wildlife. Livestock carcasses are often disposed of in supplementary feeding stations for avian scavengers, as a management and conservation tool for these species worldwide. In feeding stations, vultures and other scavengers can consume carcasses almost immediately after disposal, which implies the potential ingestion of veterinary pharmaceuticals as a non-target consequence of supplementary feeding. Using UPLC-MS/MS and HPLC-TOF, we evaluated the presence and concentration of fluoroquinolone residues in plasma of nestling vultures feeding on domestic livestock carrion. Three different fluoroquinolones (marbofloxacin, enrofloxacin and its metabolite ciprofloxacin) and a non-targeted β-lactam (nafcillin) were detected in vulture plasma. The high proportion of individuals (92%) with fluoroquinolone residues at variable concentrations (up to ∼20 μg L(-1) of enrofloxacin and ∼150 μg L(-1) of marbofloxacin) sampled in several geographically distant colonies and on different dates suggests that these and other drugs were potentially ingested throughout nestling development. Contamination with veterinary fluoroquinolones and other pharmaceuticals should be considered as an unintended but alarming consequence of food management in threatened wildlife.

  6. Electrochemical Detection of Fluoroquinolone Antibiotics in Milk Using a Magneto Immunosensor

    PubMed Central

    Pinacho, Daniel G.; Sánchez-Baeza, Francisco; Pividori, María-Isabel; Marco, María-Pilar

    2014-01-01

    An amperometric magneto-immunosensor (AMIS) for the detection of residues of fluoroquinolone antibiotics in milk samples is described for the first time. The immunosensor presented combines magnetic beads biomodified with an antibody with a broad recognition profile of fluoroquinolones, a haptenized enzyme and a magnetic graphite–epoxy composite (m-GEC) electrode. After the immunochemical reaction with specific enzyme tracer, the antibody biomodified magnetic beads are easily captured by an electrode made of graphite-epoxy composite containing a magnet, which also acts as transducer for the electrochemical detection. In spite of the complexity of milk, the use of magnetic beads allows elimination of potential interferences caused by the matrix components; hence the AMIS could perform quantitative measurements, directly in these samples, without any additional sample cleanup or extraction step. The immunosensor is able to detect up to seven different fluoroquinolones far below the MRLs defined by the UE for milk; for example ciprofloxacin is detected directly in milk with an IC50 of 0.74 μg/L and a LOD of 0.009 μg/L. This strategy offers great promise for rapid, simple, cost-effective, and on-site analysis fluoroquinolones in complex samples. PMID:25171120

  7. Biological cost of fluoroquinolone resistance in Escherichia coli implicated in polyclonal infection.

    PubMed

    Bémer, P; Corvec, S; Guitton, C; Giraudeau, C; Le Gargasson, G; Espaze, E; Drugeon, H

    2007-07-01

    Polyclonal Escherichia coli strains were isolated in a transplanted patient who experienced successive septic shocks. Fluoroquinolone susceptible and resistant strains were corresponding to different PFGE fragment profiles. The gyrA S83L mutation was associated with a reduction in biological fitness. Resistant strain was selected by a long-term single use of ofloxacin. PMID:16884861

  8. Wildlife contamination with fluoroquinolones from livestock: Widespread occurrence of enrofloxacin and marbofloxacin in vultures.

    PubMed

    Blanco, Guillermo; Junza, Alexandra; Segarra, David; Barbosa, José; Barrón, Dolores

    2016-02-01

    There is much recent interest in the presence and impact of veterinary pharmaceuticals in wildlife. Livestock carcasses are often disposed of in supplementary feeding stations for avian scavengers, as a management and conservation tool for these species worldwide. In feeding stations, vultures and other scavengers can consume carcasses almost immediately after disposal, which implies the potential ingestion of veterinary pharmaceuticals as a non-target consequence of supplementary feeding. Using UPLC-MS/MS and HPLC-TOF, we evaluated the presence and concentration of fluoroquinolone residues in plasma of nestling vultures feeding on domestic livestock carrion. Three different fluoroquinolones (marbofloxacin, enrofloxacin and its metabolite ciprofloxacin) and a non-targeted β-lactam (nafcillin) were detected in vulture plasma. The high proportion of individuals (92%) with fluoroquinolone residues at variable concentrations (up to ∼20 μg L(-1) of enrofloxacin and ∼150 μg L(-1) of marbofloxacin) sampled in several geographically distant colonies and on different dates suggests that these and other drugs were potentially ingested throughout nestling development. Contamination with veterinary fluoroquinolones and other pharmaceuticals should be considered as an unintended but alarming consequence of food management in threatened wildlife. PMID:26498102

  9. Detection of a wide variety of human and veterinary fluoroquinolone antibiotics in municipal wastewater and wastewater-impacted surface water.

    PubMed

    He, Ke; Soares, Ana Dulce; Adejumo, Hollie; McDiarmid, Melissa; Squibb, Katherine; Blaney, Lee

    2015-03-15

    As annual sales of antibiotics continue to rise, the mass of these specially-designed compounds entering municipal wastewater treatment systems has also increased. Of primary concern here is that antibiotics can inhibit growth of specific microorganisms in biological processes of wastewater treatment plants (WWTPs) or in downstream ecosystems. Growth inhibition studies with Escherichia coli demonstrated that solutions containing 1-10 μg/L of fluoroquinolones can inhibit microbial growth. Wastewater samples were collected on a monthly basis from various treatment stages of a 30 million gallon per day WWTP in Maryland, USA. Samples were analyzed for the presence of 11 fluoroquinolone antibiotics. At least one fluoroquinolone was detected in every sample. Ofloxacin and ciprofloxacin exhibited detection frequencies of 100% and 98%, respectively, across all sampling sites. Concentrations of fluoroquinolones in raw wastewater were as high as 1900 ng/L for ciprofloxacin and 600 ng/L for ofloxacin. Difloxacin, enrofloxacin, fleroxacin, moxifloxacin, norfloxacin, and orbifloxacin were also detected at appreciable concentrations of 9-170 ng/L. The total mass concentration of fluoroquinolones in raw wastewater was in the range that inhibited E. coli growth, suggesting that concerns over antibiotic presence in wastewater and wastewater-impacted surface water are valid. The average removal efficiency of fluoroquinolones during wastewater treatment was approximately 65%; furthermore, the removal efficiency for fluoroquinolones was found to be negatively correlated to biochemical oxygen demand removal and positively correlated to phosphorus removal.

  10. A study of personality factors and interaction in 4th-year dental students and their teachers.

    PubMed

    Watts, T L; Millard, L

    1997-02-01

    No previous investigation has considered dental student and teaching staff opinions on their relationship with each other. In a day when students are increasingly asked for feedback on the quality of teaching by staff, such investigations are of particular interest. This exploratory study was designed to compare the personality characteristics of a clinical year of dental students with those of the teaching staff they most frequently encountered, and to investigate these factors for possible associations with the quality of perceived teaching-learning interaction between the 2 groups. A complete 4th year of dental students (n = 87), and those teachers whom they met regularly (n = 80), were asked to participate. Subjects completed a form of the Myers-Briggs personality questionnaire simplified for use in education, and were asked to assess their relationship with persons in the other group. All the students and 75% of the staff, after follow-up, returned usable data. There was close similarity between staff and student personality profiles, and perception of working relationships by both groups was largely independent of personality factors and temperament. There were differences in staff perception of their relationship with extrovert and introvert students. Students showed minor differences in their perception of staff relationships with respect to two other personality factors. These findings indicate a substantial similarity between staff and students, and suggest a mature and stable relationship between people in the 2 groups. PMID:9567907

  11. Quality of education predicts performance on the Wide Range Achievement Test-4th Edition Word Reading subtest.

    PubMed

    Sayegh, Philip; Arentoft, Alyssa; Thaler, Nicholas S; Dean, Andy C; Thames, April D

    2014-12-01

    The current study examined whether self-rated education quality predicts Wide Range Achievement Test-4th Edition (WRAT-4) Word Reading subtest and neurocognitive performance, and aimed to establish this subtest's construct validity as an educational quality measure. In a community-based adult sample (N = 106), we tested whether education quality both increased the prediction of Word Reading scores beyond demographic variables and predicted global neurocognitive functioning after adjusting for WRAT-4. As expected, race/ethnicity and education predicted WRAT-4 reading performance. Hierarchical regression revealed that when including education quality, the amount of WRAT-4's explained variance increased significantly, with race/ethnicity and both education quality and years as significant predictors. Finally, WRAT-4 scores, but not education quality, predicted neurocognitive performance. Results support WRAT-4 Word Reading as a valid proxy measure for education quality and a key predictor of neurocognitive performance. Future research should examine these findings in larger, more diverse samples to determine their robust nature.

  12. Communicating Science to Impact Learning? A Phenomenological Inquiry into 4th and 5th Graders' Perceptions of Science Information Sources

    NASA Astrophysics Data System (ADS)

    Gelmez Burakgazi, Sevinc; Yildirim, Ali; Weeth Feinstein, Noah

    2016-04-01

    Rooted in science education and science communication studies, this study examines 4th and 5th grade students' perceptions of science information sources (SIS) and their use in communicating science to students. It combines situated learning theory with uses and gratifications theory in a qualitative phenomenological analysis. Data were gathered through classroom observations and interviews in four Turkish elementary schools. Focus group interviews with 47 students and individual interviews with 17 teachers and 10 parents were conducted. Participants identified a wide range of SIS, including TV, magazines, newspapers, internet, peers, teachers, families, science centers/museums, science exhibitions, textbooks, science books, and science camps. Students reported using various SIS in school-based and non-school contexts to satisfy their cognitive, affective, personal, and social integrative needs. SIS were used for science courses, homework/project assignments, examination/test preparations, and individual science-related research. Students assessed SIS in terms of the perceived accessibility of the sources, the quality of the content, and the content presentation. In particular, some sources such as teachers, families, TV, science magazines, textbooks, and science centers/museums ("directive sources") predictably led students to other sources such as teachers, families, internet, and science books ("directed sources"). A small number of sources crossed context boundaries, being useful in both school and out. Results shed light on the connection between science education and science communication in terms of promoting science learning.

  13. Physical activity participation by parental language use in 4th, 8th, and 11th grade students in Texas, USA.

    PubMed

    Springer, Andrew E; Lewis, Kayan; Kelder, Steven H; Fernandez, Maria E; Barroso, Cristina S; Hoelscher, Deanna M

    2010-10-01

    Research on physical activity (PA) by level of acculturation in Hispanic children is limited and findings have been mixed. We examined PA participation by primary language used with parents in a representative sample of 4th, 8th, and 11th grade Texas public school students. Mixed-effects regression models were conducted using cross-sectional data from the 2004-2005 School Physical Activity and Nutrition Study (n = 22,049). Self-reported PA was compared among three language-ethnic groups: Spanish-Hispanic (SH) (referent); English-Hispanic (EH); and English-Other (EO). EH and/or EO girls were generally between 1.25 and 2.58 [OR] times more likely to participate in PA across grade levels, with the largest differences found for school sports in 8th grade girls. EH and EO 8th grade boys were 1.71 (CI: 1.40, 2.10) and 2.06 (CI: 1.68, 2.51) times, respectively, more likely to participate in school sports. Findings indicate important disparities in Spanish-speaking Hispanic children's PA participation. PMID:19365728

  14. Exploring the contribution of efflux on the resistance to fluoroquinolones in clinical isolates of Staphylococcus aureus

    PubMed Central

    2011-01-01

    Background Antimicrobial resistance mediated by efflux systems is still poorly characterized in Staphylococcus aureus, despite the description of several efflux pumps (EPs) for this bacterium. In this work we used several methodologies to characterize the efflux activity of 52 S. aureus isolates resistant to ciprofloxacin collected in a hospital in Lisbon, Portugal, in order to understand the role played by these systems in the resistance to fluoroquinolones. Results Augmented efflux activity was detected in 12 out of 52 isolates and correlated with increased resistance to fluoroquinolones. Addition of efflux inhibitors did not result in the full reversion of the fluoroquinolone resistance phenotype, yet it implied a significant decrease in the resistance levels, regardless of the type(s) of mutation(s) found in the quinolone-resistance determining region of grlA and gyrA genes, which accounted for the remaining resistance that was not efflux-mediated. Expression analysis of the genes coding for the main efflux pumps revealed increased expression only in the presence of inducing agents. Moreover, it showed that not only different substrates can trigger expression of different EP genes, but also that the same substrate can promote a variable response, according to its concentration. We also found isolates belonging to the same clonal type that showed different responses towards drug exposure, thus evidencing that highly related clinical isolates may diverge in the efflux-mediated response to noxious agents. The data gathered by real-time fluorometric and RT-qPCR assays suggest that S. aureus clinical isolates may be primed to efflux antimicrobial compounds. Conclusions The results obtained in this work do not exclude the importance of mutations in resistance to fluoroquinolones in S. aureus, yet they underline the contribution of efflux systems for the emergence of high-level resistance. All together, the results presented in this study show the potential role

  15. Clinical implications of reduced susceptibility to fluoroquinolones in paediatric Shigella sonnei and Shigella flexneri infections

    PubMed Central

    Thompson, Corinne N.; Thieu, Nga Tran Vu; Vinh, Phat Voong; Duc, Anh Nguyen; Wolbers, Marcel; Vinh, Ha; Campbell, James I.; Ngoc, Dung Tran Thi; Hoang, Nguyen Van Minh; Thanh, Tuyen Ha; The, Hao Chung; Nguyen, To Nguyen Thi; Lan, Nguyen Phu Huong; Parry, Christopher M.; Chau, Nguyen Van Vinh; Thwaites, Guy; Thanh, Duy Pham; Baker, Stephen

    2016-01-01

    Objectives We aimed to quantify the impact of fluoroquinolone resistance on the clinical outcome of paediatric shigellosis patients treated with fluoroquinolones in southern Vietnam. Such information is important to inform therapeutic management for infections caused by this increasingly drug-resistant pathogen, responsible for high morbidity and mortality in young children globally. Methods Clinical information and bacterial isolates were derived from a randomized controlled trial comparing gatifloxacin with ciprofloxacin for the treatment of paediatric shigellosis. Time–kill experiments were performed to evaluate the impact of MIC on the in vitro growth of Shigella and Cox regression modelling was used to compare clinical outcome between treatments and Shigella species. Results Shigella flexneri patients treated with gatifloxacin had significantly worse outcomes than those treated with ciprofloxacin. However, the MICs of fluoroquinolones were not significantly associated with poorer outcome. The presence of S83L and A87T mutations in the gyrA gene significantly increased MICs of fluoroquinolones. Finally, elevated MICs and the presence of the qnrS gene allowed Shigella to replicate efficiently in vitro in high concentrations of ciprofloxacin. Conclusions We found that below the CLSI breakpoint, there was no association between MIC and clinical outcome in paediatric shigellosis infections. However, S. flexneri patients had worse clinical outcomes when treated with gatifloxacin in this study regardless of MIC. Additionally, Shigella harbouring the qnrS gene are able to replicate efficiently in high concentrations of ciprofloxacin and we hypothesize that such strains possess a competitive advantage against fluoroquinolone-susceptible strains due to enhanced shedding and transmission. PMID:26679253

  16. Fluoroquinolone-Resistant Escherichia coli Infections After Transrectal Biopsy of the Prostate in the Veterans Affairs Healthcare System

    PubMed Central

    Saade, Elie A.; Suwantarat, Nuntra; Zabarsky, Trina F.; Wilson, Brigid; Donskey, Curtis J.

    2016-01-01

    Background Recent reports suggest that infections due to fluoroquinolone-resistant Escherichia coli (E. coli) are an increasingly common complication of transrectal biopsy of the prostate (TBP) in the United States. A better understanding of the magnitude and scope of these infections is needed to guide prevention efforts. Our objective is to determine whether the incidence of infections due to fluoroquinolone-resistant E. coli after TBP has increased nationwide in the Veterans Affairs Health Care System and to identify risk factors for infection. Methods We performed a retrospective, observational cohort study and a nested case-control study within the US Deparment of Veterans Affairs Healthcare System. The primary outcomes were the incidence of urinary tract infection (UTI) and bacteremia with E. coli and with fluoroquinolone- resistant E. coli strains within 30 days after TBP. Secondary endpoints focused on the correlation between fluoroquinolone-resistance in all urinary E. coli isolates and post-TBP infection and risk factors for infection due to fluoroquinolone-resistant E. coli infection. Results 245 618 patients undergoing 302 168 TBP procedures from 2000 through 2013 were included in the cohort study, and 59 469 patients undergoing TBP from 2011 through 2013 were included in the nested case-control study. Between 2000 and 2013, there was a 5-fold increase in the incidence of E. coli UTI (0.18%–0.93%) and a 4-fold increase in the incidence of E. coli bacteremia (0.04%–0.18%) after TBP that was attributable to an increase in the incidence of fluoroquinolone- resistant E. coli UTI (0.03%–0.75%) and bacteremia (0.01%–0.14%). The increasing incidence of fluoroquinolone-resistant E. coli infections after TBP occurred in parallel with increasing rates of fluoroquinolone-resistance in all urinary E. coli isolates. By multivariable logistic regression analysis, independent risk factors for fluoroquinolone-resistant E. coli UTI after TBP included diabetes

  17. Intensity and Mechanisms of Fluoroquinolone Resistance within the H30 and H30Rx Subclones of Escherichia coli Sequence Type 131 Compared with Other Fluoroquinolone-Resistant E. coli

    PubMed Central

    Johnston, Brian; Kuskowski, Michael A.; Sokurenko, Evgeni V.; Tchesnokova, Veronika

    2015-01-01

    The recent expansion of the H30 subclone of Escherichia coli sequence type 131 (ST131) and its CTX-M-15-associated H30Rx subset remains unexplained. Although ST131 H30 typically exhibits fluoroquinolone resistance, so do multiple other E. coli lineages that have not expanded similarly. To determine whether H30 isolates have more intense fluoroquinolone resistance than other fluoroquinolone-resistant E. coli isolates and to identify possible mechanisms, we determined the MICs for four fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin, and norfloxacin) among 89 well-characterized, genetically diverse fluoroquinolone-resistant E. coli isolates (48 non-H30 and 41 H30 [23 H30Rx and 18 H30 non-Rx]). We compared the MICs with the H30 and H30Rx status, the presence/number of nonsynonymous mutations in gyrA, parC, and parE, the presence of aac(6′)-1b-cr (an aminoglycoside/fluoroquinolone agent-modifying enzyme), and the efflux pump activity (measured as organic solvent tolerance [OST]). Among 1,518 recent E. coli clinical isolates, ST131 H30 predominated clonally, both overall and among the fluoroquinolone-resistant isolates. Among the 89 study isolates, compared with non-H30 isolates, H30 isolates exhibited categorically higher MICs for all four fluoroquinolone agents, higher absolute ciprofloxacin and norfloxacin MICs, more nonsynonymous mutations in gyrA, parC, and parE (specifically gyrA D87N, parC E84V, and parE I529L), and a numerically higher prevalence of (H30Rx-associated) aac(6′)-1b-cr but lower OST scores. All putative resistance mechanisms were significantly associated with the MICs [for aac(6′)-1b-cr: ciprofloxacin and norfloxacin only]. parC D87N corresponded with ST131 H30 and parE I529L with ST131 generally. Thus, more intense fluoroquinolone resistance may provide ST131 H30, especially H30Rx [if aac(6′)-1b-cr positive], with subtle fitness advantages over other fluoroquinolone-resistant E. coli strains. This urges both parsimonious

  18. [Level of smoking of 3rd and 4th grade students studying health and related factors: follow-up study].

    PubMed

    Göktalay, Tuğba; Cengiz Özyurt, Beyhan; Sakar Coşkun, Ayşin; Celik, Pinar

    2011-01-01

    The levels of smoking of 1st and 2nd year students at Faculty of Medicine and Manisa School of Health at Celal Bayar University were investigated in 2006-2007. This study is carried out in order to see if there is a change in the same students' level of smoking while they are in 3rd and 4th year. In addition, the study aimed to examine the factors affecting the level of use and attitudes towards the law effectuated in July 19, 2009. This is a follow-up study with 80.42% return rate. A 26-item structured questionnaire was administered. The participants filled out the questionnaires under supervision of the researchers in their classrooms. The University Institutional Review Board approved the study. The total of participants (263) of the follow-up study included 189 female and 74 male. The rate of experimenting with smoking was 49% with the mean age of 15.7 (SD= 4.01 years). The mean age of experimenting with smoking was the earliest on male students studying at faculty of medicine. The level of smoking was found to be the most on females, studying at faculty of medicine and staying at the dormitory, with smoking parents (p< 0.05). The most important reason to begin smoking was curiosity (55.2%) while bad breath and yellowing of teeth were the reasons to quit (91.7%). 83.3% of the students thought that the law will be effective on quit smoking. The level of both experimenting and use of smoking has been increased over time. It is suggested that medical students' awareness about the danger of smoking should be raised at earlier grades. In addition, lectures should be offered to students at School of Health and they should be encouraged to unite in order to fight with smoking.

  19. Benefits of a 4th Ice Class in the Simulated Radar Reflectivities of Convective Systems Using a Bulk Microphysics Scheme

    NASA Technical Reports Server (NTRS)

    Lang, Stephen E.; Tao, Wei-Kuo; Chern, Jiun-Dar; Wu, Di; Li, Xiaowen

    2015-01-01

    Numerous cloud microphysical schemes designed for cloud and mesoscale models are currently in use, ranging from simple bulk to multi-moment, multi-class to explicit bin schemes. This study details the benefits of adding a 4th ice class (hail) to an already improved 3-class ice bulk microphysics scheme developed for the Goddard Cumulus Ensemble model based on Rutledge and Hobbs (1983,1984). Besides the addition and modification of several hail processes from Lin et al. (1983), further modifications were made to the 3-ice processes, including allowing greater ice super saturation and mitigating spurious evaporationsublimation in the saturation adjustment scheme, allowing graupelhail to become snow via vapor growth and hail to become graupel via riming, and the inclusion of a rain evaporation correction and vapor diffusivity factor. The improved 3-ice snowgraupel size-mapping schemes were adjusted to be more stable at higher mixing rations and to increase the aggregation effect for snow. A snow density mapping was also added. The new scheme was applied to an intense continental squall line and a weaker, loosely-organized continental case using three different hail intercepts. Peak simulated reflectivities agree well with radar for both the intense and weaker case and were better than earlier 3-ice versions when using a moderate and large intercept for hail, respectively. Simulated reflectivity distributions versus height were also improved versus radar in both cases compared to earlier 3-ice versions. The bin-based rain evaporation correction affected the squall line case more but did not change the overall agreement in reflectivity distributions.

  20. [Level of smoking of 3rd and 4th grade students studying health and related factors: follow-up study].

    PubMed

    Göktalay, Tuğba; Cengiz Özyurt, Beyhan; Sakar Coşkun, Ayşin; Celik, Pinar

    2011-01-01

    The levels of smoking of 1st and 2nd year students at Faculty of Medicine and Manisa School of Health at Celal Bayar University were investigated in 2006-2007. This study is carried out in order to see if there is a change in the same students' level of smoking while they are in 3rd and 4th year. In addition, the study aimed to examine the factors affecting the level of use and attitudes towards the law effectuated in July 19, 2009. This is a follow-up study with 80.42% return rate. A 26-item structured questionnaire was administered. The participants filled out the questionnaires under supervision of the researchers in their classrooms. The University Institutional Review Board approved the study. The total of participants (263) of the follow-up study included 189 female and 74 male. The rate of experimenting with smoking was 49% with the mean age of 15.7 (SD= 4.01 years). The mean age of experimenting with smoking was the earliest on male students studying at faculty of medicine. The level of smoking was found to be the most on females, studying at faculty of medicine and staying at the dormitory, with smoking parents (p< 0.05). The most important reason to begin smoking was curiosity (55.2%) while bad breath and yellowing of teeth were the reasons to quit (91.7%). 83.3% of the students thought that the law will be effective on quit smoking. The level of both experimenting and use of smoking has been increased over time. It is suggested that medical students' awareness about the danger of smoking should be raised at earlier grades. In addition, lectures should be offered to students at School of Health and they should be encouraged to unite in order to fight with smoking. PMID:22233305

  1. Breakfast patterns among low-income, ethnically-diverse 4th-6th grade children in an urban area

    PubMed Central

    2014-01-01

    Background Increasing school breakfast participation has been advocated as a method to prevent childhood obesity. However, little is known about children’s breakfast patterns outside of school (e.g., home, corner store). Policies that increase school breakfast participation without an understanding of children’s breakfast habits outside of school may result in children consuming multiple breakfasts and may undermine efforts to prevent obesity. The aim of the current study was to describe morning food and drink consumption patterns among low-income, urban children and their associations with relative weight. Methods A cross-sectional analysis was conducted of data obtained from 651 4th-6th graders (51.7% female, 61.2% African American, 10.7 years) in 2012. Students completed surveys at school that included all foods eaten and their locations that morning. Height and weight were measured by trained research staff. Results On the day surveyed, 12.4% of youth reported not eating breakfast, 49.8% reported eating one breakfast, 25.5% reported eating two breakfasts, and 12.3% reported eating three or more breakfasts. The number of breakfasts consumed and BMI percentile showed a significant curvilinear relationship, with higher mean BMI percentiles observed among children who did not consume any breakfast and those who consumed ≥ 3 breakfasts. Sixth graders were significantly less likely to have consumed breakfast compared to younger children. A greater proportion of obese youth had no breakfast (18.0%) compared to healthy weight (10.1%) and overweight youth (10.7%, p = .01). Conclusions When promoting school breakfast, policies will need to be mindful of both over- and under-consumption to effectively address childhood obesity and food insecurity. Clinical trial registration NCT01924130 from http://clinicaltrials.gov/. PMID:24928474

  2. Preface: Proceedings of the 4th European Conference on Neutron Scattering (Lund, Sweden, 25 29 June 2007)

    NASA Astrophysics Data System (ADS)

    Rennie, Adrian R.

    2008-03-01

    Approximately 700 delegates came to the small university city of Lund in southern Sweden at the end of June 2007 to attend the 4th European Conference on Neutron Scattering. The majority of these participants are primarily interested in specific areas of condensed matter science and use neutron techniques as a powerful tool to study the structure and dynamic behaviour of materials. These range from liquids, superconductors, magnetic materials and archaeological artefacts. The diversity of scientific problems is reflected by the attendance of many laboratories with specializations in numerous different disciplines. The maturity of the technique is shown by the fact that neutron scattering is now applied widely in so many areas. Most results from neutron scattering experiements are published as articles that primarily relate to a specific scientific discipline in the context of problem oriented research. The neutron scattering conference provided an opportunity to exchange ideas between different fields. It is hoped that this collection of papers, from participants that submitted articles on applications of neutron scattering, will continue to promote the exchange of ideas for new studies, as was seen at the conference. The papers that describe instrumentation and advances in methods of neutron scattering will appear separately in Measurement Science and Technology Worldwide activity in developing new facilities for neutron scattering and the motivation for substantial projects, such as the new target station at the ISIS facility in the UK or the proposed European Spallation Source, comes from unique information obtained from working with neutrons. The results reported in the following papers show that there is substantial exciting work still to be performed as the community of users expands into new fields. The participants, as well as the organizers, are extremely grateful to the numerous sponsors that helped to make the conference a resounding success. We are

  3. Focus on JNJ-Q2, a novel fluoroquinolone, for the management of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections

    PubMed Central

    Jones, Travis M; Johnson, Steven W; DiMondi, V Paul; Wilson, Dustin T

    2016-01-01

    JNJ-Q2 is a novel, fifth-generation fluoroquinolone that has excellent in vitro and in vivo activity against a variety of Gram-positive and Gram-negative organisms. In vitro studies indicate that JNJ-Q2 has potent activity against pathogens responsible for acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP), such as Staphylococcus aureus and Streptococcus pneumoniae. JNJ-Q2 also has been shown to have a higher barrier to resistance compared to other agents in the class and it remains highly active against drug-resistant organisms, including methicillin-resistant S. aureus, ciprofloxacin-resistant methicillin-resistant S. aureus, and drug-resistant S. pneumoniae. In two Phase II studies, the efficacy of JNJ-Q2 was comparable to linezolid for ABSSSI and moxifloxacin for CABP. Furthermore, JNJ-Q2 was well tolerated, with adverse event rates similar to or less than other fluoroquinolones. With an expanded spectrum of activity and low potential for resistance, JNJ-Q2 shows promise as an effective treatment option for ABSSSI and CABP. Considering its early stage of development, the definitive role of JNJ-Q2 against these infections and its safety profile will be determined in future Phase III studies. PMID:27354817

  4. Contribution of Target Gene Mutations and Efflux to Decreased Susceptibility of Salmonella enterica Serovar Typhimurium to Fluoroquinolones and Other Antimicrobials▿

    PubMed Central

    Chen, Sheng; Cui, Shenghui; McDermott, Patrick F.; Zhao, Shaohua; White, David G.; Paulsen, Ian; Meng, Jianghong

    2007-01-01

    The mechanisms involved in fluoroquinolone resistance in Salmonella enterica include target alterations and overexpression of efflux pumps. The present study evaluated the role of known and putative multidrug resistance efflux pumps and mutations in topoisomerase genes among laboratory-selected and naturally occurring fluoroquinolone-resistant Salmonella enterica serovar Typhimurium strains. Strains with ciprofloxacin MICs of 0.25, 4, 32, and 256 μg/ml were derived in vitro using serovar Typhimurium S21. These mutants also showed decreased susceptibility or resistance to many nonfluoroquinolone antimicrobials, including tetracycline, chloramphenicol, and several β-lactams. The expression of efflux pump genes acrA, acrB, acrE, acrF, emrB, emrD, and mdlB were substantially increased (≥2-fold) among the fluoroquinolone-resistant mutants. Increased expression was also observed, but to a lesser extent, with three other putative efflux pumps: mdtB (yegN), mdtC (yegO), and emrA among mutants with ciprofloxacin MICs of ≥32 μg/ml. Deletion of acrAB or tolC in S21 and its fluoroquinolone-resistant mutants resulted in increased susceptibility to fluoroquinolones and other tested antimicrobials. In naturally occurring fluoroquinolone-resistant serovar Typhimurium strains, deletion of acrAB or tolC increased fluoroquinolone susceptibility 4-fold, whereas replacement of gyrA double mutations (S83F D87N) with wild-type gyrA increased susceptibility >500-fold. These results indicate that a combination of topoisomerase gene mutations, as well as enhanced antimicrobial efflux, plays a critical role in the development of fluoroquinolone resistance in both laboratory-derived and naturally occurring quinolone-resistant serovar Typhimurium strains. PMID:17043131

  5. Autism: Proceedings of Annual Meeting of the National Society for Autistic Children (4th, June 22-24, 1972, Flint Michigan).

    ERIC Educational Resources Information Center

    National Society for Autistic Children, Syracuse, NY.

    Presented are proceedings of the 4th annual (1972) meeting of the National Society for Autistic Children including 11 papers given at the meeting. Listed are officers and board members of the society, the convention committee members, and recipients of citations and awards. The president's report notes past goals, accomplishments, and future…

  6. Unmet Needs of Low Academic Level Adult (0-4th Grade Level) Students: A Follow-Up Study. A Special Demonstration/Teacher Training Project. Final Report.

    ERIC Educational Resources Information Center

    Portage Township Schools, IN.

    An Indiana 310 Project was conducted to determine the needs of very low level adult basic education students (0-4th grade). Specifically, the study sought to answer the following four questions: (1) What brings low academic level students into ABE programs? (2) What aspects of the ABE programs do low academic level students dislike? (3) Why do low…

  7. Coefficients of Correlation of IQ's on the WAIS-R with Standard Age Scores on the Stanford-Binet, 4th Edition for Previously Identified Mentally Handicapped Adolescents.

    ERIC Educational Resources Information Center

    Richardson, John C.

    This paper presents a study regarding the correlation of the Stanford-Binet: 4th Edition Intelligence Quotient (IQ) scores with the Wechsler Adult Intelligence Scale-Revised (WAIS-R) IQ scores for the purpose of improving the identification process for educable mentally handicapped (EMH) school age adolescents and young adults. The sample included…

  8. Meeting Materials for the 4th NRC Meeting on the Guidance for and the Review of EPA's Toxicological Assessment of Inorganic Arsenic

    EPA Science Inventory

    On December 2-3, 2015, the National Research Council (NRC) hosted the 4th meeting of the committee formed to peer review the draft IRIS assessment of inorganic arsenic. EPA presented background and overview materials during the public session on December 2nd. This information co...

  9. U.S. Dietary and Physical Activity Guideline Knowledge and Corresponding Behaviors among 4th and 5th Grade Students: A Multi-Site Pilot Study

    ERIC Educational Resources Information Center

    Bea, Jennifer W.; Martinez, Stephanie; Armstrong-Florian, Traci; Farrell, Vanessa; Martinez, Cathy; Whitmer, Evelyn; Hartz, Vern; Blake, Samuel; Nicolini, Ariana; Misner, Scottie

    2014-01-01

    Knowledge of U.S. dietary and physical activity recommendations and corresponding behaviors were surveyed among 4th and 5th graders in five Arizona counties to determine the need for related education in SNAP-Ed eligible schools. A <70% target response rate was the criterion. Participants correctly identified recommendations for: fruit, 20%;…

  10. The Relationship of Values in Elementary School 4th Grade Social Studies Textbook with the Attainments and Their Level of Being Included in Student Workbooks

    ERIC Educational Resources Information Center

    Kilic, Abdurrahman

    2012-01-01

    In this study, the relationship of values in elementary school 4th grade Social Studies textbook with the attainments and their level of being included in student workbook are tried to be determined. Case study, which is a qualitative research method, was applied for this research. To collect data, document analysis technique, which is among the…

  11. The Effect of the Conceptual Change Oriented Instruction through Cooperative Learning on 4th Grade Students' Understanding of Earth and Sky Concepts

    ERIC Educational Resources Information Center

    Celikten, Oksan; Ipekcioglu, Sevgi; Ertepinar, Hamide; Geban, Omer

    2012-01-01

    The purpose of this study was to compare the effectiveness of the conceptual change oriented instruction through cooperative learning (CCICL) and traditional science instruction (TI) on 4th grade students' understanding of earth and sky concepts and their attitudes toward earth and sky concepts. In this study, 56 fourth grade students from the…

  12. Examining Differentiation and Utilization of iPads across Content Areas in an Independent, PreK-4th Grade Elementary School

    ERIC Educational Resources Information Center

    Milman, Natalie B.; Carlson-Bancroft, Angela; Vanden Boogart, Amy

    2014-01-01

    This mixed methods case study examined the implementation of a 1:1 iPad initiative in a suburban, co-educational, independent, preK-4th grade elementary school in the United States. This article focuses on how teachers used iPads to differentiate instruction and across multiple content areas. Findings show the processes by which teachers employed…

  13. Nation and Language: Modern Aspects of Socio-Linguistic Development. Proceedings of the 4th International Conference (Lithuania, October 21-22, 2010)

    ERIC Educational Resources Information Center

    Online Submission, 2010

    2010-01-01

    The 4th international conference "Nation and Language: Modern Aspects of Socio-Linguistic Development" continues an eight-year old tradition. The conference is organized by Kaunas University of Technology Panevezys Institute and aims to bring scientists and researchers together for a general scientific discussion on new trends in sociolinguistic,…

  14. Fluoroquinolone and Macrolide Exposure Predict Clostridium difficile Infection with the Highly Fluoroquinolone- and Macrolide-Resistant Epidemic C. difficile Strain BI/NAP1/027.

    PubMed

    Wieczorkiewicz, Jeffrey T; Lopansri, Bert K; Cheknis, Adam; Osmolski, James R; Hecht, David W; Gerding, Dale N; Johnson, Stuart

    2015-11-02

    Antibiotics have been shown to influence the risk of infection with specific Clostridium difficile strains as well as the risk of C. difficile infection (CDI). We performed a retrospective case-control study of patients infected with the epidemic BI/NAP1/027 strain in a U.S. hospital following recognition of increased CDI severity and culture of stools positive by C. difficile toxin immunoassay. Between 2005 and 2007, 72% (103/143) of patients with first-episode CDIs were infected with the BI strain by restriction endonuclease analysis (REA) typing. Most patients received multiple antibiotics within 6 weeks of CDI onset (median of 3 antibiotic classes). By multivariate analysis, fluoroquinolone and macrolide exposure was more frequent among BI cases than among non-BI-infected controls (odds ratio [OR] for fluoroquinolones, 3.2; 95% confidence interval [CI], 1.3 to 7.5; (P < 0.001; OR for macrolides, 5.2; 95% CI, 1.1 to 24.0; P = 0.04)). In contrast, clindamycin use was less frequent among the BI cases than among the controls (OR, 0.1; 95% CI, 0.03 to 0.4; P = 0.001). High-level resistance to moxifloxacin and azithromycin was more frequent among BI strains (moxifloxacin, 49/102 [48%] BI versus 0/40 non-BI, P = 0.0001; azithromycin, 100/102 [98%] BI versus 22/40 [55%] non-BI, P = 0.0001). High-level resistance to clindamycin was more frequent among non-BI strains (22/40 [55%] non-BI versus 7/102 [7%] BI, P = 0.0001). Fluoroquinolone use, macrolide use, and C. difficile resistance to these antibiotic classes were associated with infection by the epidemic BI strain of C. difficile in a U.S. hospital during a time when CDI rates were increasing nationally due to the highly fluoroquinolone-resistant BI/NAP1/027 strain.

  15. Fluoroquinolone and Macrolide Exposure Predict Clostridium difficile Infection with the Highly Fluoroquinolone- and Macrolide-Resistant Epidemic C. difficile Strain BI/NAP1/027

    PubMed Central

    Wieczorkiewicz, Jeffrey T.; Lopansri, Bert K.; Cheknis, Adam; Osmolski, James R.; Hecht, David W.; Gerding, Dale N.

    2015-01-01

    Antibiotics have been shown to influence the risk of infection with specific Clostridium difficile strains as well as the risk of C. difficile infection (CDI). We performed a retrospective case-control study of patients infected with the epidemic BI/NAP1/027 strain in a U.S. hospital following recognition of increased CDI severity and culture of stools positive by C. difficile toxin immunoassay. Between 2005 and 2007, 72% (103/143) of patients with first-episode CDIs were infected with the BI strain by restriction endonuclease analysis (REA) typing. Most patients received multiple antibiotics within 6 weeks of CDI onset (median of 3 antibiotic classes). By multivariate analysis, fluoroquinolone and macrolide exposure was more frequent among BI cases than among non-BI-infected controls (odds ratio [OR] for fluoroquinolones, 3.2; 95% confidence interval [CI], 1.3 to 7.5; (P < 0.001; OR for macrolides, 5.2; 95% CI, 1.1 to 24.0; P = 0.04)). In contrast, clindamycin use was less frequent among the BI cases than among the controls (OR, 0.1; 95% CI, 0.03 to 0.4; P = 0.001). High-level resistance to moxifloxacin and azithromycin was more frequent among BI strains (moxifloxacin, 49/102 [48%] BI versus 0/40 non-BI, P = 0.0001; azithromycin, 100/102 [98%] BI versus 22/40 [55%] non-BI, P = 0.0001). High-level resistance to clindamycin was more frequent among non-BI strains (22/40 [55%] non-BI versus 7/102 [7%] BI, P = 0.0001). Fluoroquinolone use, macrolide use, and C. difficile resistance to these antibiotic classes were associated with infection by the epidemic BI strain of C. difficile in a U.S. hospital during a time when CDI rates were increasing nationally due to the highly fluoroquinolone-resistant BI/NAP1/027 strain. PMID:26525793

  16. Fluoroquinolone Resistance Mechanism of Clinical Isolates and Selected Mutants of Pasteurella multocida from Bovine Respiratory Disease in China

    PubMed Central

    KONG, Ling-Cong; GAO, Duo; GAO, Yun-Hang; LIU, Shu-Ming; MA, Hong-Xia

    2014-01-01

    The minimum inhibitory concentrations (MICs), mutation prevention concentrations (MPCs) and contribution of quinolone resistance-determining region (QRDR) mutations to fluoroquinolone (ciprofloxacin, enrofloxacin and orbifloxacin) susceptibility in 23 Pasteurella multocida (Pm) isolates were investigated. Fluoroquinolone-susceptible isolates (MICs ≤0.25 µg/ml, 9 isolates) had no QRDR mutations, and their respective MPCs were low. Fluoroquinolone-intermediate isolates (MICs=0.5 µg/ml, 14 isolates) had QRDR mutations (Asp87 to Asn or Ala84 to Pro in gyrA), and their respective MPCs were high (4–32 µg/ml). First-step mutants (n=5) and laboratory-derived highly resistant fluoroquinolone mutants (n=5) also had QRDR mutations. The MICs of fluoroquinolones for mutant-derived strains were decreased in the presence of efflux inhibitors. The results indicated that the fluoroquinolone resistance of Pm is mainly due to multiple target gene mutations in gyrA and parC and the overexpression of efflux pump genes. PMID:25649952

  17. Fluoroquinolone resistance mechanism of clinical isolates and selected mutants of Pasteurella multocida from bovine respiratory disease in China.

    PubMed

    Kong, Ling-Cong; Gao, Duo; Gao, Yun-Hang; Liu, Shu-Ming; Ma, Hong-Xia

    2014-12-01

    The minimum inhibitory concentrations (MICs), mutation prevention concentrations (MPCs) and contribution of quinolone resistance-determining region (QRDR) mutations to fluoroquinolone (ciprofloxacin, enrofloxacin and orbifloxacin) susceptibility in 23 Pasteurella multocida (Pm) isolates were investigated. Fluoroquinolone-susceptible isolates (MICs ≤0.25 µg/ml, 9 isolates) had no QRDR mutations, and their respective MPCs were low. Fluoroquinolone-intermediate isolates (MICs=0.5 µg/ml, 14 isolates) had QRDR mutations (Asp87 to Asn or Ala84 to Pro in gyrA), and their respective MPCs were high (4-32 µg/ml). First-step mutants (n=5) and laboratory-derived highly resistant fluoroquinolone mutants (n=5) also had QRDR mutations. The MICs of fluoroquinolones for mutant-derived strains were decreased in the presence of efflux inhibitors. The results indicated that the fluoroquinolone resistance of Pm is mainly due to multiple target gene mutations in gyrA and parC and the overexpression of efflux pump genes.

  18. Molecular characterization of fluoroquinolone-resistant Aeromonas spp. isolated from imported shrimp.

    PubMed

    Shakir, Zakiya; Khan, Saeed; Sung, Kidon; Khare, Sangeeta; Khan, Ashraf; Steele, Roger; Nawaz, Mohamed

    2012-11-01

    Sixty-three nalidixic acid-resistant Aeromonas sp. isolates were obtained from imported shrimp. Phylogenetic analysis of gyrB sequences indicated that 18 were A. enteropelogenes, 26 were A. caviae, and 19 were A. sobria. Double missense mutations in the quinolone resistance-determining region (QRDR) of gyrA at codon 83 (Ser→Val/Ile) and codon 92 (Leu→Met) coupled with a point mutation of parC at codon 80 (Ser→Ile/Phe) conferred high levels of quinolone resistance in the isolates. A majority of A. enteropelogenes and A. caviae strains harbored toxin genes, whereas only a few A. sobria strains harbored these genes. The fluoroquinolone-resistant Aeromonas spp. exhibited higher cytotoxicity than fluoroquinolone-sensitive, virulent Aeromonas spp. to rat epithelial cells.

  19. A Case of Fluoroquinolone-Resistant Leprosy Discovered after 9 Years of Misdiagnosis.

    PubMed

    Raharolahy, Onivola; Ramarozatovo, Lala S; Ranaivo, Irina M; Sendrasoa, Fandresena A; Andrianarison, Malalaniaina; Andrianarivelo, Mala Rakoto; Cambau, Emmanuelle; Rabenja, Fahafahantsoa Rapelanoro

    2016-01-01

    We report a case of misdiagnosed leprosy in a 21-year-old Malagasy male, who, improperly treated, developed secondary mycobacterial resistance to fluoroquinolone. The patient contracted the infection 9 years prior to the current consultation, displaying on the right thigh a single papulonodular lesion, which progressively spread to the lower leg, back, and face. Initial administration of ciprofloxacin and prednisolone led to temporary and fluctuating improvement. Subsequent long-term self-medication with ciprofloxacin and corticosteroid did not heal the foul and nonhealing ulcers on the legs and under the right sole. Histopathological findings were compatible with lepromatous leprosy. Skin biopsy was positive for acid-fast bacilli and PCR assay confirmed the presence of a fluoroquinolone-resistant strain of Mycobacterium leprae (gyrA A91V). After 6 months of standard regimen with rifampicin, clofazimine, and dapsone, clinical outcome significantly improved. Clinical characteristics and possible epidemiological implications are discussed. PMID:27579195

  20. A Case of Fluoroquinolone-Resistant Leprosy Discovered after 9 Years of Misdiagnosis

    PubMed Central

    Ramarozatovo, Lala S.; Ranaivo, Irina M.; Andrianarison, Malalaniaina; Cambau, Emmanuelle

    2016-01-01

    We report a case of misdiagnosed leprosy in a 21-year-old Malagasy male, who, improperly treated, developed secondary mycobacterial resistance to fluoroquinolone. The patient contracted the infection 9 years prior to the current consultation, displaying on the right thigh a single papulonodular lesion, which progressively spread to the lower leg, back, and face. Initial administration of ciprofloxacin and prednisolone led to temporary and fluctuating improvement. Subsequent long-term self-medication with ciprofloxacin and corticosteroid did not heal the foul and nonhealing ulcers on the legs and under the right sole. Histopathological findings were compatible with lepromatous leprosy. Skin biopsy was positive for acid-fast bacilli and PCR assay confirmed the presence of a fluoroquinolone-resistant strain of Mycobacterium leprae (gyrA A91V). After 6 months of standard regimen with rifampicin, clofazimine, and dapsone, clinical outcome significantly improved. Clinical characteristics and possible epidemiological implications are discussed. PMID:27579195

  1. Short communication: Fluoroquinolone susceptibility of Staphylococcus aureus strains isolated from caprine clinical mastitis in southeast Spain.

    PubMed

    Marín, P; Escudero, E; Fernández-Varón, E; Cárceles, C M; Corrales, J C; Gómez-Martín, A; Martínez, I

    2010-11-01

    The antibiotic susceptibility of 32 strains of Staphylococcus aureus isolated from the mastitic milk of dairy goats was evaluated. The antibiotics tested were 3 fluoroquinolones that have been developed especially for use in veterinary medicine: danofloxacin, marbofloxacin, and orbifloxacin. Minimum inhibitory concentration (MIC) tests were performed according to the microdilution broth method. The MIC(90) (concentration at which 90% inhibition is achieved) values obtained were 0.5, 1, and 1 mg/L for danofloxacin, marbofloxacin, and orbifloxacin, respectively. Danofloxacin was the most active fluoroquinolone tested against Staph. aureus strains isolated from milk; however, specific testing is required before using these drugs as therapy for the control of clinical mammary infections in goats.

  2. Photodegradation products of a new antibacterial fluoroquinolone derivative, orbifloxacin, in aqueous solution.

    PubMed

    Morimura, T; Nobuhara, Y; Matsukura, H

    1997-02-01

    A new antibacterial fluoroquinolone derivative, orbifloxacin (ORFX), is decomposed photochemically in aqueous solution. When ORFX solution was irradiated with a chemical lamp or sunlight, three major photodegradation products were isolated by preparative HPLC. These degradation products were identified by electron-impact mass spectrometry, liquid-secondary-ion mass spectrometry and 1-H-NMR spectroscopy. Moreover, the photodegradation pathway was investigated by a similar study using several fluoroquinolone derivatives which were presumed to be the intermediates of the photoreaction of the ORFX. Consequently, it was found that two main photochemical reactions, the decomposition of the dimethylpiperazinyl moiety and the elimination of the cyclopropyl group, take place in ORFX. The detected structures of photodegradation products and the photodegradation studies of the postulated intermediates suggested that the photodecomposition of the dimethylpiperazinyl ring at the 7-position and the elimination of the cyclopropyl group at the 1-position occurred concurrently with the release of fluorine at the 8-position.

  3. Synthesis and biological properties of conjugates between fluoroquinolones and a N3''-functionalized pyochelin.

    PubMed

    Noël, Sabrina; Gasser, Véronique; Pesset, Bénédicte; Hoegy, Françoise; Rognan, Didier; Schalk, Isabelle J; Mislin, Gaëtan L A

    2011-12-21

    Pyochelin is a siderophore common to Pseudomonas aeruginosa and several other pathogenic bacteria. A pyochelin functionalized at the N3'' position with a propyl-amine extension was previously synthesized. In the present work we proved that this analog binds FptA, the pyochelin outer membrane receptor, and transports iron(III) efficiently into bacteria. This functionalized pyochelin seemed to be a good candidate for antibiotic vectorization in the framework of a Trojan horse prodrug strategy. In this context, conjugates between pyochelin and three fluoroquinolones (norfloxacin, ciprofloxacin and N-desmethyl-ofloxacin) were synthesized with a spacer arm that was either stable or hydrolyzable in vivo. Some pyochelin-fluoroquinolone conjugates had antibacterial activities in growth inhibition experiments on several P. aeruginosa strains. However, these activities were weaker than those of the antibiotic alone. These properties appeared to be related to both the solubility and bioavailability of conjugates and to the stability of the spacer arm used. PMID:22052022

  4. A Brief Boot Camp for 4th-Year Medical Students Entering into Pediatric and Family Medicine Residencies

    PubMed Central

    Adler, Mark; Mangold, Karen; Trainor, Jennifer

    2016-01-01

    The transition from medical student to intern is a challenging process characterized by a steep learning curve. Focused courses targeting skills necessary for success as a resident have increased self-perceived preparedness, confidence, and medical knowledge. Our aim was to create a brief educational intervention for 4th-year medical students entering pediatric, family practice, and medicine/pediatric residencies to target skills necessary for an internship. The curriculum used a combination of didactic presentations, small group discussions, role-playing, facilitated debriefing, and simulation-based education. Participants completed an objective structured clinical exam requiring synthesis and application of multiple boot camp elements before and after the elective. Participants completed anonymous surveys assessing self-perceived preparedness for an internship, overall and in regards to specific skills, before the elective and after the course. Participants were asked to provide feedback about the course. Using checklists to assess performance, students showed an improvement in performing infant lumbar punctures (47.2% vs 77.0%; p < 0.01, 95% CI for the difference 0.2, 0.4%) and providing signout (2.5 vs. 3.9 (5-point scale) p < 0.01, 95% CI for the difference 0.6, 2.3). They did not show an improvement in communication with a parent. Participants demonstrated an increase in self-reported preparedness for all targeted skills, except for obtaining consults and interprofessional communication. There was no increase in reported overall preparedness. All participants agreed with the statements, “The facilitators presented the material in an effective manner,” “I took away ideas I plan to implement in internship,” and “I think all students should participate in a similar experience.” When asked to assess the usefulness of individual modules, all except order writing received a mean Likert score > 4. A focused boot camp addressing key knowledge and skills

  5. PREFACE: 9th World Congress on Computational Mechanics and 4th Asian Pacific Congress on Computational Mechanics

    NASA Astrophysics Data System (ADS)

    Khalili, N.; Valliappan, S.; Li, Q.; Russell, A.

    2010-07-01

    The use for mathematical models of natural phenomena has underpinned science and engineering for centuries, but until the advent of modern computers and computational methods, the full utility of most of these models remained outside the reach of the engineering communities. Since World War II, advances in computational methods have transformed the way engineering and science is undertaken throughout the world. Today, theories of mechanics of solids and fluids, electromagnetism, heat transfer, plasma physics, and other scientific disciplines are implemented through computational methods in engineering analysis, design, manufacturing, and in studying broad classes of physical phenomena. The discipline concerned with the application of computational methods is now a key area of research, education, and application throughout the world. In the early 1980's, the International Association for Computational Mechanics (IACM) was founded to promote activities related to computational mechanics and has made impressive progress. The most important scientific event of IACM is the World Congress on Computational Mechanics. The first was held in Austin (USA) in 1986 and then in Stuttgart (Germany) in 1990, Chiba (Japan) in 1994, Buenos Aires (Argentina) in 1998, Vienna (Austria) in 2002, Beijing (China) in 2004, Los Angeles (USA) in 2006 and Venice, Italy; in 2008. The 9th World Congress on Computational Mechanics is held in conjunction with the 4th Asian Pacific Congress on Computational Mechanics under the auspices of Australian Association for Computational Mechanics (AACM), Asian Pacific Association for Computational Mechanics (APACM) and International Association for Computational Mechanics (IACM). The 1st Asian Pacific Congress was in Sydney (Australia) in 2001, then in Beijing (China) in 2004 and Kyoto (Japan) in 2007. The WCCM/APCOM 2010 publications consist of a printed book of abstracts given to delegates, along with 247 full length peer reviewed papers published with

  6. Emergence of a Streptococcus pneumoniae clinical isolate highly resistant to telithromycin and fluoroquinolones.

    PubMed

    Faccone, Diego; Andres, Patricia; Galas, Marcelo; Tokumoto, Marta; Rosato, Adriana; Corso, Alejandra

    2005-11-01

    Streptococcus pneumoniae is a major pathogen causing community-acquired pneumonia and acute bronchitis. Macrolides, fluoroquinolones (FQs), and, recently, telithromycin (TEL) constitute primary therapeutic options, and rare cases of resistance have been reported. In this report, we describe the emergence of an S. pneumoniae clinical isolate with high-level TEL resistance (MIC, 256 microg/ml) and simultaneous resistance to FQs. Ongoing studies are oriented to elucidate the precise mechanism of resistance to TEL.

  7. Fluoroquinolones in the Wenyu River catchment, China: Occurrence simulation and risk assessment.

    PubMed

    Hao, Xuewen; Cao, Yan; Zhang, Lai; Zhang, Yongyong; Liu, Jianguo

    2015-12-01

    Concern is increasing regarding the environmental impact of the high usage rate and intensive release of antibiotics used for human and animal therapy in major urban areas of China. In the present study, regional environmental distribution simulations and risk assessments for 3 commonly used fluoroquinolones in the Wenyu River catchment were conducted using a typical catchment model widely used in Europe. The fluoroquinolone antibiotics investigated (ofloxacin, norfloxacin, and ciprofloxacin) are consumed at high levels for personal health care in China. These antibiotics were simulated in the aquatic environment of the Wenyu River catchment across the Beijing City area for annual average concentrations, with regional predicted environmental concentrations (PECs) of approximately 711 ng/L, 55.3 ng/L, and 22.2 ng/L and local PECs up to 1.8 µg/L, 116 ng/L, and 43 ng/L, respectively. Apart from hydrological conditions, the concentrations of fluoroquinolones were associated closely with the sewage treatment plants (STPs) and their serving population, as well as hospital distributions. The presence of these fluoroquinolones in the catchment area of the present study showed significant characteristics of the occurrence of pharmaceuticals in the aquatic environment in an urban river, with typical "down-the-drain" chemicals. Significantly high concentrations of specific antibiotics indicated non-negligible risks caused by the intensive use in the local aquatic environment in a metropolitan area, particularly ofloxacin in upstream Shahe Reservoir, middle stream and downstream Qing River, and Liangma River to the Ba River segment. Specific treatment measures for these pharmaceuticals and personal care products in STPs are required for such metropolitan areas. PMID:26178666

  8. Independent behavior of commensal flora for carriage of fluoroquinolone-resistant bacteria in patients at admission.

    PubMed

    de Lastours, Victoire; Chau, Françoise; Tubach, Florence; Pasquet, Blandine; Ruppé, Etienne; Fantin, Bruno

    2010-12-01

    The important role of commensal flora as a natural reservoir of bacterial resistance is now well established. However, whether the behavior of each commensal flora is similar to that of other floras in terms of rates of carriage and risk factors for bacterial resistance is unknown. During a 6-month period, we prospectively investigated colonization with fluoroquinolone-resistant bacteria in the three main commensal floras from hospitalized patients at admission, targeting Escherichia coli in the fecal flora, coagulase-negative Staphylococcus (CNS) in the nasal flora, and α-hemolytic streptococci in the pharyngeal flora. Resistant strains were detected on quinolone-containing selective agar. Clinical and epidemiological data were collected. A total of 555 patients were included. Carriage rates of resistance were 8.0% in E. coli, 30.3% in CNS for ciprofloxacin, and 27.2% in streptococci for levofloxacin; 56% of the patients carried resistance in at least one flora but only 0.9% simultaneously in all floras, which is no more than random. Risk factors associated with the carriage of fluoroquinolone-resistant strains differed between fecal E. coli (i.e., colonization by multidrug-resistant bacteria) and nasal CNS (i.e., age, coming from a health care facility, and previous antibiotic treatment with a fluoroquinolone) while no risk factors were identified for pharyngeal streptococci. Despite high rates of colonization with fluoroquinolone-resistant bacteria, each commensal flora behaved independently since simultaneous carriage of resistance in the three distinct floras was uncommon, and risk factors differed. Consequences of environmental selective pressures vary in each commensal flora according to its local specificities (clinical trial NCT00520715 [http://clinicaltrials.gov/ct2/show/NCT00520715]).

  9. Impact of fluoroquinolone resistance in Gram-negative bloodstream infections on healthcare utilization.

    PubMed

    Brigmon, M M; Bookstaver, P Brandon; Kohn, J; Albrecht, H; Al-Hasan, M N

    2015-09-01

    There has been a concerning increase in fluoroquinolone resistance among Gram-negative bloodstream isolates. This retrospective cohort study examines the implications of fluoroquinolone resistance on use of healthcare resources in patients with Gram-negative bloodstream infections (BSI). Hospitalized adults with first episodes of community-onset Gram-negative BSI from 2010 to 2012 at Palmetto Health Hospitals in Columbia, SC, USA were identified. Multivariate linear regression was used to examine risk factors for prolonged hospital length of stay (HLOS) in survivors of Gram-negative BSI. Among 474 unique patients, 384 (81%) and 90 (19%) had BSI due to fluoroquinolone-susceptible (FQ-S) and fluoroquinolone non-susceptible (FQ-NS) Gram-negative bacilli, respectively. The FQ-NS bloodstream isolates, particularly Escherichia coli, were more likely than FQ-S isolates to be multi-drug resistant (56% versus 6%, p < 0.001). Compared with patients with BSI due to FQ-S bloodstream isolates, those with FQ-NS isolates were more likely to receive inappropriate empirical antimicrobial therapy (26% versus 3%, p < 0.001), have longer mean HLOS (11.6 versus 9.3 days, p 0.03) and treatment duration with intravenous antibiotics during hospitalization (9.1 versus 7.1 days, p 0.001), and use outpatient intravenous antibiotics at hospital discharge (15% versus 8%, p 0.05). After adjustments in the multivariate model, inappropriate empirical antimicrobial therapy was an independent risk factor for prolonged HLOS in survivors of Gram-negative BSI (parameter estimate 3.65 days, 95% CI 0.43-6.86). Multi-drug resistance among FQ-NS bloodstream isolates limits both empirical and definitive antimicrobial treatment options and poses excessive burdens on the healthcare system.

  10. Synthesis and antibacterial evaluation of a novel tricyclic oxaborole-fused fluoroquinolone.

    PubMed

    Li, Xianfeng; Zhang, Yong-Kang; Plattner, Jacob J; Mao, Weimin; Alley, M R K; Xia, Yi; Hernandez, Vincent; Zhou, Yasheen; Ding, Charles Z; Li, Jinpeng; Shao, Zhijun; Zhang, Hongwei; Xu, Musheng

    2013-02-15

    We have designed and synthesized a novel class of compounds based on fluoroquinolone antibacterial prototype. The design concept involved the replacement of the 3-carboxylic acid in ciprofloxacin with an oxaborole-fused ring as an acid-mimicking group. The synthetic method employed in this work provides a good example of incorporating boron atom in complex molecules with multiple functional groups. The antibacterial activity of the newly synthesized compounds has been evaluated. PMID:23312945

  11. Ciprofloxacin-resistant Campylobacter persists in raw retail chicken after the fluoroquinolone ban.

    PubMed

    Nannapaneni, Ramakrishna; Hanning, Irene; Wiggins, Keith C; Story, Robert P; Ricke, Steven C; Johnson, Michael G

    2009-10-01

    In 2005, the FDA withdrew approval for the use of fluoroquinolones in live poultry production. To assess any changes in countable numbers of ciprofloxacin-resistant Campylobacter before and after the fluoroquinolone withdrawal, retail whole raw chicken carcasses (RTCC) purchased in Northwest Arkansas from 2004 to 2006 were sampled for this purpose. Using a previously published direct-plating method developed in our laboratory, we quantified trends of Campylobacter and ciprofloxacin-resistant Campylobacter loads by direct plating whole chicken carcass rinses on Campylobacter agar (CA) or Campylobacter agar containing 8.6 mg/ml ciprofloxacin (CCA). Countable populations of Campylobacter were recovered from 74, 96, and 63% of carcasses sampled in 2004, 2005, and 2006 respectively. The percentages of carcasses with minimum detectable levels of ciprofloxacin-resistant Campylobacter were 20, 42 and 33%, sampled in 2004, 2005 and 2006, respectively. Our 3 year analysis in one geographical area indicated a persistence of Campylobacter and ciprofloxacin-resistant Campylobacter on retail raw chicken carcasses despite the cessation of fluoroquinolone use in poultry production. PMID:21462579

  12. Dissimilar Fitness Associated with Resistance to Fluoroquinolones Influences Clonal Dynamics of Various Multiresistant Bacteria

    PubMed Central

    Fuzi, Miklos

    2016-01-01

    Fitness cost associated with resistance to fluoroquinolones was recently shown to vary across clones of methicillin-resistant Staphylococcus aureus and extended-spectrum β-lactamase-producing Klebsiella pneumoniae. The resulting dissimilar fitness should have influenced the clonal dynamics and thereby the rates of resistance for these pathogens. Moreover, a similar mechanism was recently proposed for the emergence of the H30 and H30R lineages of ESBL-producing E. coli and the major international clone (ribotype 027) of Clostridium difficile. Furthermore, several additional international clones of various multiresistant bacteria are suspect to have been selected by an analogous process. An ability to develop favorable mutations in the gyrase and topoisomerase IV genes seems to be a prerequisite for pathogens to retain fitness while showing high-level resistance to fluoroquinolones. Since, the consumption of other “non-fluoroquinolone” groups of antibiotics have also contributed to the rise in resistance rates a more judicious use of antibiotics in general and of fluoroquinolones in particular could ameliorate the international resistance situation. PMID:27458434

  13. Triprotic site-specific acid-base equilibria and related properties of fluoroquinolone antibacterials.

    PubMed

    Rusu, Aura; Tóth, Gergő; Szőcs, Levente; Kökösi, József; Kraszni, Márta; Gyéresi, Árpád; Noszál, Béla

    2012-07-01

    The complete macro- and microequilibrium analyses of six fluoroquinolone drugs - ciprofloxacin, enrofloxacin, norfloxacin, pefloxacin, ofloxacin and moxifloxacin - are presented. Previous controversial literature data are straightened up, the protonation centers are unambiguously identified, and the protonation macro- and microconstant values are reported. The macroconstants were determined by (1)H NMR-pH titrations while the microconstants were determined by a multi-modal spectroscopic-deductive methodology, in which methyl ester derivatives were synthesized and their NMR-pH titration data contributed to the evaluation of all the microconstants. The full (1)H, (13)C and (15)N NMR assignments, NMR-pH profiles, macro- and microprotonation schemes and species-specific diagrams are included. Our studies show that the fluoroquinolones have three protonation centers: the carboxylate group, the N-1' and N-4' piperazine nitrogens and concentration of the uncharged microspecies is way below the values published earlier. The results could be well interpreted in terms of structural properties. The protonation macro- and microconstant values allow the pre-planned method development in techniques such as capillary zone electrophoresis and also, the interpretation of fluoroquinolone mechanism of biological action, including the pharmacokinetic properties, and antibacterial activities that are all heavily influenced by the states of protonation.

  14. Microcolonies in fluoroquinolone agar proportion susceptibility testing of Mycobacterium tuberculosis: an indicator of drug resistance

    PubMed Central

    Blackman, A.; May, S.; Devasia, R. A.; Maruri, F.; Stratton, C.

    2014-01-01

    Microcolony growth of Mycobacterium tuberculosis on agar proportion susceptibility testing is neither well-defined nor previously reported with fluoroquinolone susceptibility testing. We describe here M. tuberculosis microcolony growth with fluoroquinolones, and assess its clinical significance. We screened 797M. tuberculosis isolates for ofloxacin resistance (2.0 µg/mL) by agar proportion; 19 ofloxacin-resistant and 38 ofloxacin-susceptible isolates were selected for more detailed susceptibility testing with ofloxacin, ciprofloxacin, levofloxacin (all at 2.0 µg/mL) and moxifloxacin (0.5 µg/mL). The 57 isolates were also tested at two concentrations both above and below the critical concentrations. Microcolonies were defined as colonies 0.2–0.4 mm in diameter; confirmed microcolonies were present on repeat testing. Of the 57 isolates tested in detail, 7 grew microcolonies, of which 2 (0.3% of all isolates tested) had confirmed microcolonies on repeat testing (6 tests performed, and microcolonies were present on at least 4). Both M. tuberculosis isolates were ofloxacin-resistant on screening, and had ofloxacin minimum inhibitory concentration (MIC) >8 µg/mL. The five other isolates were ofloxacin-susceptible on screening, but had regular colony growth (i.e., resistance) at the drug concentration that initially resulted in microcolonies (ofloxacin 0.5 or 1.0 µg/mL). Microcolonies were observed infrequently with fluoroquinolone susceptibility testing, but when confirmed, they were associated with drug resistance. PMID:22322359

  15. Suppression of gyrase-mediated resistance by C7 aryl fluoroquinolones.

    PubMed

    Malik, Muhammad; Mustaev, Arkady; Schwanz, Heidi A; Luan, Gan; Shah, Nirali; Oppegard, Lisa M; de Souza, Ernane C; Hiasa, Hiroshi; Zhao, Xilin; Kerns, Robert J; Drlica, Karl

    2016-04-20

    Fluoroquinolones form drug-topoisomerase-DNA complexes that rapidly block transcription and replication. Crystallographic and biochemical studies show that quinolone binding involves a water/metal-ion bridge between the quinolone C3-C4 keto-acid and amino acids in helix-4 of the target proteins, GyrA (gyrase) and ParC (topoisomerase IV). A recent cross-linking study revealed a second drug-binding mode in which the other end of the quinolone, the C7 ring system, interacts with GyrA. We report that addition of a dinitrophenyl (DNP) moiety to the C7 end of ciprofloxacin (Cip-DNP) reduced protection due to resistance substitutions in Escherichia coli GyrA helix-4, consistent with the existence of a second drug-binding mode not evident in X-ray structures of drug-topoisomerase-DNA complexes. Several other C7 aryl fluoroquinolones behaved in a similar manner with particular GyrA mutants. Treatment of E. coli cultures with Cip-DNP selectively enriched an uncommon variant, GyrA-A119E, a change that may impede binding of the dinitrophenyl group at or near the GyrA-GyrA interface. Collectively the data support the existence of a secondary quinolone-binding mode in which the quinolone C7 ring system interacts with GyrA; the data also identify C7 aryl derivatives as a new way to obtain fluoroquinolones that overcome existing GyrA-mediated quinolone resistance. PMID:26984528

  16. Multiresidue determination of fluoroquinolones in shrimp by liquid chromatography-fluorescence-mass spectrometry.

    PubMed

    Schneider, Marilyn J; Vazquez-Moreno, Luz; Bermudez-Almada, Maria del Carmen; Guardado, Ramon Barraza; Ortega-Nieblas, Magdalena

    2005-01-01

    An efficient multiresidue method for analysis of fluoroquinolones in shrimp has been developed in which quantitation by fluorescence and confirmation by Multiple Stage Mass Spectrometry (MS) is achieved simultaneously. In this method, shrimp tissue is extracted with ammoniacal acetonitrile and the extract is defatted and then evaporated. After dissolution in basic phosphate buffer, fluoroquinolones in the extract are separated by liquid chromatography and quantitated, taking advantage of their intense fluorescence. Eluate from the fluorescence detector enters the MS, which allows for confirmation by monitoring ratios of 2 prominent product ions in the MS3 or MS2 spectrum. Using this method, 8 fluoroquinolones have been analyzed in shrimp samples fortified at 10, 25, 50, or 100 ppb levels. Recoveries for desethyleneciprofloxacin, norfloxacin, ciprofloxacin, danofloxacin, enrofloxacin, orbifloxacin, sarafloxacin, and difloxacin ranged from 75 to 92%, with relative standard deviation values of <6%. The limits of quantitation ranged from 0.1 to 1 ng/g. Enrofloxacin and ciprofloxacin were also successfully determined in enrofloxacin-incurred shrimp using this method.

  17. Multiresidue analysis of fluoroquinolone antibiotics in chicken tissue using liquid chromatography-fluorescence-multiple mass spectrometry.

    PubMed

    Schneider, Marilyn J; Donoghue, Dan J

    2002-11-15

    An efficient liquid chromatographic method for the multiresidue analysis of fluoroquinolone antibiotics in chicken tissue has been developed in which quantitation using fluorescence and confirmation with multiple mass spectrometry (MS(n)) was achieved simultaneously. Using this method, eight fluoroquinolones were analyzed in fortified samples of chicken liver and muscle tissue with recoveries at levels of 10-200 ng/g generally in the range of 60-93%, except for desethylene ciprofloxacin, which consistently gave recoveries >or=45%. Relative standard deviations were excellent in all cases, and the limits of detection in ng/g were determined as follows in liver and (muscle): desethylene ciprofloxacin 0.3 (0.1), norfloxacin 1.2 (0.2), ciprofloxacin 2 (1.5), danofloxacin 0.2 (0.1), enrofloxacin 0.3 (0.2), orbifloxacin 1.5 (0.5), sarafloxacin 2 (0.6), difloxacin 0.3 (0.2). Confirmation of the identities of the fluoroquinolones was achieved by monitoring the ratios of two prominent product ions in MS(2) (desethylene ciprofloxacin) or MS(3) (all others). Levels of confirmation as related to ion ratio variability criteria were established. Enrofloxacin and ciprofloxacin were also determined in enrofloxacin incurred chicken liver and muscle using this method.

  18. Suppression of gyrase-mediated resistance by C7 aryl fluoroquinolones

    PubMed Central

    Malik, Muhammad; Mustaev, Arkady; Schwanz, Heidi A.; Luan, Gan; Shah, Nirali; Oppegard, Lisa M.; de Souza, Ernane C.; Hiasa, Hiroshi; Zhao, Xilin; Kerns, Robert J.; Drlica, Karl

    2016-01-01

    Fluoroquinolones form drug-topoisomerase-DNA complexes that rapidly block transcription and replication. Crystallographic and biochemical studies show that quinolone binding involves a water/metal-ion bridge between the quinolone C3-C4 keto-acid and amino acids in helix-4 of the target proteins, GyrA (gyrase) and ParC (topoisomerase IV). A recent cross-linking study revealed a second drug-binding mode in which the other end of the quinolone, the C7 ring system, interacts with GyrA. We report that addition of a dinitrophenyl (DNP) moiety to the C7 end of ciprofloxacin (Cip-DNP) reduced protection due to resistance substitutions in Escherichia coli GyrA helix-4, consistent with the existence of a second drug-binding mode not evident in X-ray structures of drug-topoisomerase-DNA complexes. Several other C7 aryl fluoroquinolones behaved in a similar manner with particular GyrA mutants. Treatment of E. coli cultures with Cip-DNP selectively enriched an uncommon variant, GyrA-A119E, a change that may impede binding of the dinitrophenyl group at or near the GyrA-GyrA interface. Collectively the data support the existence of a secondary quinolone-binding mode in which the quinolone C7 ring system interacts with GyrA; the data also identify C7 aryl derivatives as a new way to obtain fluoroquinolones that overcome existing GyrA-mediated quinolone resistance. PMID:26984528

  19. Generations.

    PubMed

    Chambers, David W

    2005-01-01

    Groups naturally promote their strengths and prefer values and rules that give them an identity and an advantage. This shows up as generational tensions across cohorts who share common experiences, including common elders. Dramatic cultural events in America since 1925 can help create an understanding of the differing value structures of the Silents, the Boomers, Gen Xers, and the Millennials. Differences in how these generations see motivation and values, fundamental reality, relations with others, and work are presented, as are some applications of these differences to the dental profession. PMID:16623137

  20. [In vitro activity of trovafloxacin, of other fluoroquinolones and of related antimicrobials against clinical isolates. Grupo colaborativo WHONET-Argentina].

    PubMed

    Rossi, A; Galas, M; Tokumoto, M; Guelfand, L; Lopardo, H

    1999-01-01

    The in vitro activity of trovafloxacin (TRV) has been evaluated in comparison with that of other antimicrobial agents against 5671 clinical isolates recovered by representative institutions of different provinces in our country. The resistance percentage to gentamicin and third generation cephalosporins among enterobacteriaceae was high: 17% and 16% respectively, with a considerable variation according to the analyzed species. The resistance to ciprofloxacin (CIP) and TRV affected approximately 9% of the isolates, without significant differences between both drugs. Fluoroquinolones (FQ) presented excellent activity on 166 isolates of Salmonella spp., 208 of Shigella flexneri and 76 of Shigella sonnei, where only one S.sonnei isolate was resistant to CIP, but susceptible to TRV. About half the isolates of Salmonella spp. and S.sonnei and almost all S.flexneri isolates were resistant to ampicillin, and more than 60% of Shigella spp. isolates were resistant to trimethoprim-sulfamethoxazole. A 41% of Staphylococcus aureus and 55% of coagulase-negative staphylococci isolates were resistant to oxacillin, presenting a highly associated multi-resistance. The resistance to FQ was also strongly related to oxacillin resistance, but the resistance to TRV was significantly lower than the CIP resistance: 9% vs 57% for S.aureus and 4% vs 41% for coagulase-negative staphylococci. A similar behavior was observed with Enterococcus spp., where 54% of the isolates were resistant to norfloxacin and only 13% were resistant to TRV. Neither Streptococcus pneumoniae (n = 193) nor Haemophilus influenzae (n = 139) isolates presented resistant to TRV.

  1. Genetic characterization of fluoroquinolone-resistant Escherichia coli associated with bovine mastitis in India

    PubMed Central

    Balakrishnan, Sangeetha; Antony, Prabhakar Xavier; Mukhopadhyay, Hirak Kumar; Pillai, Raghavan Madhusoodanan; Thanislass, Jacob; Padmanaban, Vijayalakshmi; Srinivas, Mouttou Vivek

    2016-01-01

    Aim: The present study was undertaken to characterize the mutation in gyrA (DNA gyrase) and parC (topoisomerase IV) genes responsible for fluoroquinolone resistance in Escherichia coli isolates associated with the bovine mastitis. Materials and Methods: A total of 92 milk samples from bovine mastitis cases were sampled in and around Puducherry (Southern India). Among these samples, 30 isolates were bacteriologically characterized as E. coli. Minimum inhibitory concentrations (MIC) of fluoroquinolones of these 30 E. coli isolates were evaluated by resazurin microtiter assay. Then, the quinolone resistance determining region (QRDR) (gyrA and parC genes) of these E. coli isolates was genetically analyzed for determining the chromosomal mutation causing fluoroquinolone resistance. Results: E. coli isolates showed a resistance rate of 63.33%, 23.33% and 30.03% to nalidixic acid, ciprofloxacin and enrofloxacin, respectively. Mutations were found at 83rd and 87th amino acid position of gyrA gene, and at 80th and 108th amino acid position of parC gene in our study isolates. Among these five isolates, one had a single mutation at 83 amino acid position of gyrA with reduced susceptibility (0.5 µg/ml) to ciprofloxacin. Then, in remaining four isolates, three isolates showed triple mutation (at gyrA: S83⟶L and D87⟶N; at parC: S80⟶I) and the fifth isolate showed an additional mutation at codon 108 of parC (A108⟶T) with the increased ciprofloxacin MIC of 16-128 µg/ml. The most common mutation noticed were at S83⟶L and D87⟶N of gyrA and S80⟶I of ParC. Conclusion: The study confirms the presence of mutation/s responsible for fluoroquinolone resistance in QRDR of gyrA and parC genes of E. coli isolates of animal origin, and there is increased rate of fluoroquinolone resistance with high-level of MIC. The mutations observed in this study were similar to that of human isolates. PMID:27536030

  2. Comparison of rhodomine-WT and sodium chloride tracer transport in a 4th order arctic river

    NASA Astrophysics Data System (ADS)

    Smull, E. M.; Wlostowski, A. N.; Gooseff, M. N.; Bowden, W. B.; Wollheim, W. M.

    2012-12-01

    Conservative tracers are useful for tracking a parcel of water through a river reach and understanding tracer transport phenomena (i.e. advection, dispersion, and transient storage). Rhodomine- WT (RWT) and sodium chloride (NaCl) are two popular stream tracers. NaCl is considered to be conservative and relatively inexpensive, yet it cannot be detected at very low concentrations. On the other hand, RWT can be detected at very low concentrations (<0.1 ppb), but it is known to photo-degrade and sorb to organic materials. Previous work has compared these tracers with small-scale laboratory analyses and field experiments on small headwater streams. The limitations and advantages to each of these tracers, as applied to large river slug injections, are not clearly understood. This work seeks to answer the following questions: 1) Does RWT improve the tracer window of detection (time of tracer arrival to time of tracer non-detection), compared to NaCl? 2) Are there differences in the late-time tailing behavior of each tracer? More specifically, can we compare RWT and NaCl breakthrough curve tail shapes to understand processes contributing to late time solute transport (transient storage or sorption-desorption)? During the summer of 2012, combined slug additions of RWT and NaCl were injected into a 1.5-kilometer reach on the Kuparuk River, a 4th order tundra river underlain by continuous permafrost located on Alaska's North Slope. Fluorescence and electrical conductivity were continuously logged at the upstream and downstream ends of the reach. Preliminary results show that the window of detection is expanded when using RWT under both high and low flow conditions by 0.2 times the advective transport timescale. Tail shapes are more similar under higher discharge conditions and dissimilar under lower discharge conditions. For example, using an exponential regression model (c(t) = eat) to quantify tail shapes, at Q = 500 l/s the exponential coefficient ratio, aRWT:aNaCl, is 0

  3. Fluoroquinolone-resistance mechanisms and phylogenetic background of clinical Escherichia coli strains isolated in south-east Poland.

    PubMed

    Korona-Glowniak, Izabela; Skrzypek, Kinga; Siwiec, Radosław; Wrobel, Andrzej; Malm, Anna

    2016-09-01

    Fluorochinolones are a class of broad-spectrum antimicrobials in the treatment of several infections, including those caused by Escherichia coli. Due to the increasing resistance of bacteria to antimicrobials, an understanding of fluoroquinolone resistance is important for infection control. The aim of this study was to determine susceptibility of clinical E. coli strains to fluoroquinolones and characterize their mechanisms of quinolone resistance. Totally, 79 non-duplicate clinical E. coli isolates included in this study were mainly from skin lesion -36 (45.6%) isolates; 54 (68.4%) isolates were assigned to phylogenetic B2 group. Resistance to ciprofloxacin was found in 20 isolates. In the quinolone resistance-determining region (QRDR) region of gyrA and parC, 4 types of point mutations were detected. Mutations in parC gene were found in all strains with gyrA mutations. Predominance of double mutation in codon 83 and 87 of gyrA (90%) and in codon 80 of parC (90%) was found. Moreover, plasmid-mediated quinolone resistance (PMRQ) determinants (qnrA or qnrB and/or aac(6')-Ib-cr) were present in 5 (25%) out of 20 fluoroquinolone-resistant isolates. Resistance to fluoroquinolones in all of the tested clinical E. coli isolates correlated with point mutations in both gyrA and parC. The majority of fluoroquinolone-resistant strains belonged to D and B2 phylogenetic groups. PMID:27602420

  4. Fluoroquinolone Efflux in Streptococcus suis Is Mediated by SatAB and Not by SmrA ▿

    PubMed Central

    Escudero, Jose Antonio; San Millan, Alvaro; Gutierrez, Belen; Hidalgo, Laura; La Ragione, Roberto M.; AbuOun, Manal; Galimand, Marc; Ferrándiz, María José; Domínguez, Lucas; de la Campa, Adela G.; Gonzalez-Zorn, Bruno

    2011-01-01

    Streptococcus suis is an emerging zoonotic pathogen. With the lack of an effective vaccine, antibiotics remain the main tool to fight infections caused by this pathogen. We have previously observed a reserpine-sensitive fluoroquinolone (FQ) efflux phenotype in this species. Here, SatAB and SmrA, two pumps belonging to the ATP binding cassette (ABC) and the major facilitator superfamily (MFS), respectively, have been analyzed in the fluoroquinolone-resistant clinical isolate BB1013. Genes encoding these pumps were overexpressed either constitutively or in the presence of ciprofloxacin in this strain. These genes could not be cloned in plasmids in Escherichia coli despite strong expression repression. Finally, site-directed insertion of smrA and satAB in the amy locus of the Bacillus subtilis chromosome using ligated PCR amplicons allowed for the functional expression and study of both pumps. Results showed that SatAB is a narrow-spectrum fluoroquinolone exporter (norfloxacin and ciprofloxacin), susceptible to reserpine, whereas SmrA was not involved in fluoroquinolone resistance. Chromosomal integration in Bacillus is a novel method for studying efflux pumps from Gram-positive bacteria, which enabled us to demonstrate the possible role of SatAB, and not SmrA, in fluoroquinolone efflux in S. suis. PMID:21930876

  5. Global Phenotypic Characterization of Effects of Fluoroquinolone Resistance Selection on the Metabolic Activities and Drug Susceptibilities of Clostridium perfringens Strains.

    PubMed

    Park, Miseon; Rafii, Fatemeh

    2014-01-01

    Fluoroquinolone resistance affects toxin production of Clostridium perfringens strains differently. To investigate the effect of fluoroquinolone resistance selection on global changes in metabolic activities and drug susceptibilities, four C. perfringens strains and their norfloxacin-, ciprofloxacin-, and gatifloxacin-resistant mutants were compared in nearly 2000 assays, using phenotype microarray plates. Variations among mutant strains resulting from resistance selection were observed in all aspects of metabolism. Carbon utilization, pH range, osmotic tolerance, and chemical sensitivity of resistant strains were affected differently in the resistant mutants depending on both the bacterial genotype and the fluoroquinolone to which the bacterium was resistant. The susceptibilities to gentamicin and erythromycin of all resistant mutants except one increased, but some resistant strains were less susceptible to amoxicillin, cefoxitin, ceftriaxone, chloramphenicol, and metronidazole than their wild types. Sensitivity to ethidium bromide decreased in some resistant mutants and increased in others. Microarray analysis of two gatifloxacin-resistant mutants showed changes in metabolic activities that were correlated with altered expression of various genes. Both the chemical structures of fluoroquinolones and the genomic makeup of the wild types influenced the changes found in resistant mutants, which may explain some inconsistent reports of the effects of therapeutic use of fluoroquinolones on clinical isolates of bacteria. PMID:25587280

  6. Guest Editor's introduction: Selected papers from the 4th USENIX Conference on Object-Oriented Technologies and Systems

    NASA Astrophysics Data System (ADS)

    Sventek, Joe

    1998-12-01

    Hewlett-Packard Laboratories, 1501 Page Mill Road, Palo Alto, CA 94304, USA Introduction The USENIX Conference on Object-Oriented Technologies and Systems (COOTS) is held annually in the late spring. The conference evolved from a set of C++ workshops that were held under the auspices of USENIX, the first of which met in 1989. Given the growing diverse interest in object-oriented technologies, the C++ focus of the workshop eventually became too narrow, with the result that the scope was widened in 1995 to include object-oriented technologies and systems. COOTS is intended to showcase advanced R&D efforts in object-oriented technologies and software systems. The conference emphasizes experimental research and experience gained by using object-oriented techniques and languages to build complex software systems that meet real-world needs. COOTS solicits papers in the following general areas: application of, and experiences with, object-oriented technologies in particular domains (e.g. financial, medical, telecommunication); the architecture and implementation of distributed object systems (e.g. CORBA, DCOM, RMI); object-oriented programming and specification languages; object-oriented design and analysis. The 4th meeting of COOTS was held 27 - 30 April 1998 at the El Dorado Hotel, Santa Fe, New Mexico, USA. Several tutorials were given. The technical program proper consisted of a single track of six sessions, with three paper presentations per session. A keynote address and a provocative panel session rounded out the technical program. The program committee reviewed 56 papers, selecting the best 18 for presentation in the technical sessions. While we solicit papers across the spectrum of applications of object-oriented technologies, this year there was a predominance of distributed, object-oriented papers. The accepted papers reflected this asymmetry, with 15 papers on distributed objects and 3 papers on object-oriented languages. The papers in this special issue are

  7. Amino acid substitutions in GyrA and ParC are associated with fluoroquinolone resistance in Mycoplasma bovis isolates from Japanese dairy calves.

    PubMed

    Sato, Toyotaka; Okubo, Torahiko; Usui, Masaru; Higuchi, Hidetoshi; Tamura, Yutaka

    2013-01-01

    We investigated the contribution of quinolone resistance-determining region (QRDR) mutations to fluoroquinolone (enrofloxacin, orbifloxacin and danofloxacin) susceptibility in 58 Mycoplasma bovis isolates from dairy cattle in Japan. Fluoroquinolone non-resistant isolates (fluoroquinolone-MICs≤2 μg/ml) possessed no QRDR mutations (19 isolates) or Ser83Leu in GyrA (32 isolates). Fluoroquinolone-resistant isolates (fluoroquinolone-MICs≥4 μg/ml) possessed Ser83Leu in GyrA and Ser81Pro in ParC (3 isolates) or Ser83Phe in GyrA and Ser80Ile in ParC (4 isolates). Laboratory-derived fluoroquinolone-resistant mutants selected from 2 isolates (possessing Ser83Leu in GyrA) had an amino acid substitution in ParC at the same position (Ser80Ile or Ser81Tyr) as fluoroquinolone-resistant isolates, suggesting a concurrent amino acid substitution in ParC (Ser80 or Ser81) is important in fluoroquinolone resistance in M. bovis isolates.

  8. Trihydroxamate Siderophore-Fluoroquinolone Conjugates are Selective Sideromycin Antibiotics that Target Staphylococcus aureus

    PubMed Central

    Wencewicz, Timothy A.; Long, Timothy E.; Möllmann, Ute; Miller, Marvin J.

    2013-01-01

    Siderophores are multidentate iron(III) chelators used by bacteria for iron assimilation. Sideromycins, also called siderophore-antibiotic conjugates, are a unique subset of siderophores that enter bacterial cells via siderophore uptake pathways and deliver the toxic antibiotic in a ‘Trojan Horse’ fashion. Sideromycins represent a novel antibiotic delivery technology with untapped potential for developing sophisticated microbe-selective antibacterial agents that limit the emergence of bacterial resistance. The chemical synthesis of a series of mono-, bis-, and trihydroxamate sideromycins are described here along with their biological evaluation in antibacterial susceptibility assays. The linear hydroxamate siderophores used for the sideromycins in this study were derived from the ferrioxamine family and inspired by the naturally occurring salmycin sideromycins. The antibacterial agents used were a β-lactam carbacepholosporin, Lorabid®, and a fluoroquinolone, ciprofloxacin, chosen for the different locations of their biological targets, the periplasm (extracellular) and the cytoplasm (intracellular). The linear hydroxamate-based sideromycins were selectively toxic towards Gram-positive bacteria, especially Staphylococcus aureus SG511 (MIC = 1.0 µM for the trihydroxamate-fluoroquinolone sideromycin). Siderophore-sideromycin competition assays demonstrated that only the fluoroquinolone sideromycins required membrane transport to reach their cytoplasmic biological target and that a trihydroxamate siderophore backbone was required for protein-mediated active transport of the sideromycins into S. aureus cells via siderophore uptake pathways. This work represents a comprehensive study of linear hydroxamate sideromycins and teaches how to build effective hydroxamate-based sideromycins as Gram-positive selective antibiotic agents. PMID:23350642

  9. The Antibiotic Susceptibility Patterns of Uropathogenic Escherichia Coli, With Special Reference to the Fluoroquinolones

    PubMed Central

    Shariff V A, Abdul Rahaman; Shenoy M, Suchitra; Yadav, Taruna; M, Radhakrishna

    2013-01-01

    Context: The emergence of drug resistance to trimethoprim-sulfamethoxazole, the penicillins, cephalosporins, and fluoroquinolones by Uropathogenic Escherichia coli (UPEC) has limited the options for selecting the appropriate antibiotic for the treatment of urinary tract infections. Aims: The The E. coli isolates, which were obtained from the culture of urine samples,were studied for their antibiotic resistance patterns, with special reference to the antimicrobial activity of the fluoroquinolones and the production of the extended spectrum β-lactamases. (ESBL), Settings and Design: This was a hospital based, prospective study which was done for a period of eighteen months. Material and Methods: This study was done by using the standard culture techniques for urine samples, the modified Kirby-Bauer disk diffusion method for the antibiotic susceptibility testing and the disk diffusion method to confirm the ESBL production by the clinical isolates of E. coli in urine. The sensitivity pattern was correlated with the clinical condition and the presence of the risk factors. The statistical analysis which was used: The statistical analysis was done by using the proportions of sensitive, resistant and intermediates. Descriptive statistics like the total, mean and percentage were done by using the Statistical Package for the Social Sciences (SPSS), version 15.0. Results: The hospital isolates showed high degrees of resistance to the penicillins, cephalosporins, nalidixic acid and the fluoroquinolones, with 59% of the isolates being ESBL producers. Conclusions: The incidence of the multidrug resistant strains of Escherichia coli has been steadily increasing over the past few years. The knowledge on the resistance pattern of the bacterial strains in a geographical area will help in guiding the appropriate and the judicious use of antibiotics. Also, the formulation of an appropriate hospital antibiotic policy will go a long way in controlling these infections. PMID:23905095

  10. The co-selection of fluoroquinolone resistance genes in the gut flora of Vietnamese children.

    PubMed

    Vien, Le Thi Minh; Minh, Ngo Ngoc Quang; Thuong, Tang Chi; Khuong, Huynh Duy; Nga, Tran Vu Thieu; Thompson, Corinne; Campbell, James I; de Jong, Menno; Farrar, Jeremy J; Schultsz, Constance; van Doorn, H Rogier; Baker, Stephen

    2012-01-01

    Antimicrobial consumption is one of the major contributing factors facilitating the development and maintenance of bacteria exhibiting antimicrobial resistance. Plasmid-mediated quinolone resistance (PMQR) genes, such as the qnr family, can be horizontally transferred and contribute to reduced susceptibility to fluoroquinolones. We performed an observational study, investigating the copy number of PMQR after antimicrobial therapy. We enrolled 300 children resident in Ho Chi Minh City receiving antimicrobial therapy for acute respiratory tract infections (ARIs). Rectal swabs were taken on enrollment and seven days subsequently, counts for Enterobacteriaceae were performed and qnrA, qnrB and qnrS were quantified by using real-time PCR on metagenomic stool DNA. On enrollment, we found no association between age, gender or location of the participants and the prevalence of qnrA, qnrB or qnrS. Yet, all three loci demonstrated a proportional increase in the number of samples testing positive between day 0 and day 7. Furthermore, qnrB demonstrated a significant increase in copy number between paired samples (p<0.001; Wilcoxon rank-sum), associated with non-fluoroquinolone combination antimicrobial therapy. To our knowledge, this is the first study describing an association between the use of non-fluoroquinolone antimicrobials and the increasing relative prevalence and quantity of qnr genes. Our work outlines a potential mechanism for the selection and maintenance of PMQR genes and predicts a strong effect of co-selection of these resistance determinants through the use of unrelated and potentially unnecessary antimicrobial regimes. PMID:22937000

  11. The Co-Selection of Fluoroquinolone Resistance Genes in the Gut Flora of Vietnamese Children

    PubMed Central

    Vien, Le Thi Minh; Minh, Ngo Ngoc Quang; Thuong, Tang Chi; Khuong, Huynh Duy; Nga, Tran Vu Thieu; Thompson, Corinne; Campbell, James I.; de Jong, Menno; Farrar, Jeremy J.; Schultsz, Constance; van Doorn, H. Rogier; Baker, Stephen

    2012-01-01

    Antimicrobial consumption is one of the major contributing factors facilitating the development and maintenance of bacteria exhibiting antimicrobial resistance. Plasmid-mediated quinolone resistance (PMQR) genes, such as the qnr family, can be horizontally transferred and contribute to reduced susceptibility to fluoroquinolones. We performed an observational study, investigating the copy number of PMQR after antimicrobial therapy. We enrolled 300 children resident in Ho Chi Minh City receiving antimicrobial therapy for acute respiratory tract infections (ARIs). Rectal swabs were taken on enrollment and seven days subsequently, counts for Enterobacteriaceae were performed and qnrA, qnrB and qnrS were quantified by using real-time PCR on metagenomic stool DNA. On enrollment, we found no association between age, gender or location of the participants and the prevalence of qnrA, qnrB or qnrS. Yet, all three loci demonstrated a proportional increase in the number of samples testing positive between day 0 and day 7. Furthermore, qnrB demonstrated a significant increase in copy number between paired samples (p<0.001; Wilcoxon rank-sum), associated with non-fluoroquinolone combination antimicrobial therapy. To our knowledge, this is the first study describing an association between the use of non-fluoroquinolone antimicrobials and the increasing relative prevalence and quantity of qnr genes. Our work outlines a potential mechanism for the selection and maintenance of PMQR genes and predicts a strong effect of co-selection of these resistance determinants through the use of unrelated and potentially unnecessary antimicrobial regimes. PMID:22937000

  12. Fluoroquinolone interactions with Mycobacterium tuberculosis gyrase: Enhancing drug activity against wild-type and resistant gyrase

    PubMed Central

    Aldred, Katie J.; Kerns, Robert J.; Berger, James M.; Osheroff, Neil

    2016-01-01

    Mycobacterium tuberculosis is a significant source of global morbidity and mortality. Moxifloxacin and other fluoroquinolones are important therapeutic agents for the treatment of tuberculosis, particularly multidrug-resistant infections. To guide the development of new quinolone-based agents, it is critical to understand the basis of drug action against M. tuberculosis gyrase and how mutations in the enzyme cause resistance. Therefore, we characterized interactions of fluoroquinolones and related drugs with WT gyrase and enzymes carrying mutations at GyrAA90 and GyrAD94. M. tuberculosis gyrase lacks a conserved serine that anchors a water–metal ion bridge that is critical for quinolone interactions with other bacterial type II topoisomerases. Despite the fact that the serine is replaced by an alanine (i.e., GyrAA90) in M. tuberculosis gyrase, the bridge still forms and plays a functional role in mediating quinolone–gyrase interactions. Clinically relevant mutations at GyrAA90 and GyrAD94 cause quinolone resistance by disrupting the bridge–enzyme interaction, thereby decreasing drug affinity. Fluoroquinolone activity against WT and resistant enzymes is enhanced by the introduction of specific groups at the C7 and C8 positions. By dissecting fluoroquinolone–enzyme interactions, we determined that an 8-methyl-moxifloxacin derivative induces high levels of stable cleavage complexes with WT gyrase and two common resistant enzymes, GyrAA90V and GyrAD94G. 8-Methyl-moxifloxacin was more potent than moxifloxacin against WT M. tuberculosis gyrase and displayed higher activity against the mutant enzymes than moxifloxacin did against WT gyrase. This chemical biology approach to defining drug–enzyme interactions has the potential to identify novel drugs with improved activity against tuberculosis. PMID:26792518

  13. The Conference on Empirical Research in Black Psychology. (4th, La Jolla, California, January 7-9, 1979).

    ERIC Educational Resources Information Center

    Cross, William E., Jr.; Harrison, Algea

    This conference proceedings contains the texts of eighteen papers which were presented at the Fourth Annual Conference on Empirical Research in Black Psychology. A small group of young black psychologists came together to critique and present research papers, to generate intellectual support for research projects that have not caught the fancy of…

  14. Proceedings of the 1980 IPMAAC Conference on Public Personnel Assessment (4th, Boston, Massachusetts, July 6-10, 1980).

    ERIC Educational Resources Information Center

    International Personnel Management Association, Washington, DC.

    The International Personnel Management Association Assessment Council (IPMAAC) contains over 500 psychometric specialists, personnel psychologists, and personnel staffing specialists dedicated to the improvement of public personnel assessment in such fields as selection and performance evaluation. Author-generated summaries/outlines of papers…

  15. Free-radical-induced oxidative and reductive degradation of fluoroquinolone pharmaceuticals: kinetic studies and degradation mechanism.

    PubMed

    Santoke, Hanoz; Song, Weihua; Cooper, William J; Greaves, John; Miller, George E

    2009-07-01

    Fluoroquinolones, as a class of broad-spectrum antibiotics, have been detected in both surface and ground waters, and advanced oxidation/reduction processes (AO/RPs) are currently in development to remove these and other pharmaceuticals from wastewater because currently utilized treatment methods have proven to be ineffective. This article reports the reaction kinetics of six common fluoroquinolones with hydroxyl radicals and hydrated electrons, which are the major reactive species involved in AO/RPs. The bimolecular reaction rate constants (M(-1) s(-1)) for orbifloxacin, flumequine, marbofloxacin, danofloxacin, enrofloxacin, and the model compound, 6-fluoro-4-oxo-1,4-dihydro-3-quinoline carboxylic acid, with *OH are (6.94 +/- 0.08) x 10(9), (8.26 +/- 0.28) x 10(9), (9.03 +/- 0.39) x 10(9), (6.15 +/- 0.11) x 10(9), (7.95 +/- 0.23) x 10(9), (7.65 +/- 0.20) x 10(9), and with e(aq)(-), (2.25 +/- 0.02) x 10(10), (1.83 +/- 0.01) x 10(10), (2.41 +/- 0.02) x 10(10), (1.68 +/- 0.02) x 10(10), (1.89 +/- 0.02) x 10(10), and (1.49 +/- 0.01) x 10(10). These rate constants are related to the functional groups attached to the quinolone core, particularly the steric hindrance of the piperazine ring, making it possible to obtain a preliminary estimate of the *OH rate constant of an arbitrary fluoroquinolone by observing the ring constituents. In addition, the products of gamma-irradiation degradation of fluoroquinolones were analyzed by LC-MS to elucidate the probable pathways of AO/RPs degradation. Results indicate that preliminary degradation pathways include hydroxyl radical attack on the aromatic ring with subsequent hydroxylation, the substitution of a fluorine atom with a hydroxyl group, and the removal of the piperazine-derived side chain.

  16. Electroluminescence imaging of Morgan Solar Inc.'s 4th generation CPV technology for in-line quality control and optical efficiency estimation

    NASA Astrophysics Data System (ADS)

    Sinclair, Michael; Dufour, Pascal; Drew, Kristine; Myrskog, Stefan; Morgan, John Paul

    2014-10-01

    An electroluminescence test for a Concentrated PV system is presented with the objective of capturing high resolution pseudo-efficiency maps that highlight optical defects in the concentrator system. Key parameters of the experimental setup and imaging system are presented. Image processing is discussed, including comparison of experimental to nominal results and the quantitative estimation of optical efficiency. Efficiency estimates are validated using measurements under a collimated solar simulator and ray-tracing software. Further validation is performed by comparison of the electroluminescence technique to direct mapping of the optical efficiency. Initial results indicate the mean estimation error for Isc is -2.4% with a standard deviation is 6.9% and a combined measurement and analysis time of less than 5 seconds per optic. An extension of this approach to in-line quality control is discussed.

  17. Topoisomerase Inhibitors: Fluoroquinolone Mechanisms of Action and Resistance.

    PubMed

    Hooper, David C; Jacoby, George A

    2016-01-01

    Quinolone antimicrobials are widely used in clinical medicine and are the only current class of agents that directly inhibit bacterial DNA synthesis. Quinolones dually target DNA gyrase and topoisomerase IV binding to specific domains and conformations so as to block DNA strand passage catalysis and stabilize DNA-enzyme complexes that block the DNA replication apparatus and generate double breaks in DNA that underlie their bactericidal activity. Resistance has emerged with clinical use of these agents and is common in some bacterial pathogens. Mechanisms of resistance include mutational alterations in drug target affinity and efflux pump expression and acquisition of resistance-conferring genes. Resistance mutations in one or both of the two drug target enzymes are commonly in a localized domain of the GyrA and ParC subunits of gyrase and topoisomerase IV, respectively, and reduce drug binding to the enzyme-DNA complex. Other resistance mutations occur in regulatory genes that control the expression of native efflux pumps localized in the bacterial membrane(s). These pumps have broad substrate profiles that include other antimicrobials as well as quinolones. Mutations of both types can accumulate with selection pressure and produce highly resistant strains. Resistance genes acquired on plasmids confer low-level resistance that promotes the selection of mutational high-level resistance. Plasmid-encoded resistance is because of Qnr proteins that protect the target enzymes from quinolone action, a mutant aminoglycoside-modifying enzyme that also modifies certain quinolones, and mobile efflux pumps. Plasmids with these mechanisms often encode additional antimicrobial resistances and can transfer multidrug resistance that includes quinolones. PMID:27449972

  18. [History of the 4th Department of Internal Medicine of the First Faculty of Medicine at Charles University and the General University Hospital in Prague].

    PubMed

    Bartůněk, Petr

    2016-01-01

    In 2015, the doctors and nurses of the 4th Department of Internal Medicine of the First Faculty of Medicine, Charles University and the General University Hospital in Prague celebrated the 70th anniversary of its founding. The article summarizes the clinics contribution to the field of internal medicine, and particularly to angiology, hepatogastroenterology and lipidology. It comments the clinics current activities and the possibilities of its further development. Attention is also paid to the tradition of high ethical and professional standards of medical care in accordance with the norms established by the clinic's founder, prof. MUDr. Bohumil Prusík.

  19. [Tumors of the 4th ventricle and the craniospinal transitional zone. Review of patients of the Neurosurgical Clinic of the Department of Medicine of the Karl Marx University].

    PubMed

    Niebeling, H G; Fried, H; Goldhahn, W E; Skrzypczak, J; Brachmann, J; Eichler, I

    1983-01-01

    From a total of 1,028 infratentorial tumours operated on at the Neurosurgical Hospital of the Section Medicine of the Karl-Marx University Leipzig in the last 30 years, 167 tumours in the region of the 4th ventrical have been selected. Their statistical processing was carried out with respect to specific localisation, average age, kind of tumour, sex, clinical findings, duration of case history, application of instrumental diagnostic procedures and radicality of operation, success and failure. Some fundamental conclussions are drawn. A subdivision in detail will be contained in the following articles based on this material.

  20. Synergistic anti-Campylobacter jejuni activity of fluoroquinolone and macrolide antibiotics with phenolic compounds

    PubMed Central

    Oh, Euna; Jeon, Byeonghwa

    2015-01-01

    The increasing resistance of Campylobacter to clinically important antibiotics, such as fluoroquinolones and macrolides, is a serious public health problem. The objective of this study is to investigate synergistic anti-Campylobacter jejuni activity of fluoroquinolones and macrolides in combination with phenolic compounds. Synergistic antimicrobial activity was measured by performing a checkerboard assay with ciprofloxacin and erythromycin in the presence of 21 phenolic compounds. Membrane permeability changes in C. jejuni by phenolic compounds were determined by measuring the level of intracellular uptake of 1-N-phenylnaphthylamine (NPN). Antibiotic accumulation assays were performed to evaluate the level of ciprofloxacin accumulation in C. jejuni. Six phenolic compounds, including p-coumaric acid, sinapic acid, caffeic acid, vanillic acid, gallic acid, and taxifolin, significantly increased the susceptibility to ciprofloxacin and erythromycin in several human and poultry isolates. The synergistic antimicrobial effect was also observed in ciprofloxacin- and erythromycin-resistant C. jejuni strains. The phenolic compounds also substantially increased membrane permeability and antibiotic accumulation in C. jejuni. Interestingly, some phenolic compounds, such as gallic acid and taxifolin, significantly reduced the expression of the CmeABC multidrug efflux pump. Phenolic compounds increased the NPN accumulation in the cmeB mutant, indicating phenolic compounds may affect the membrane permeability. In this study, we successfully demonstrated that combinational treatment of C. jejuni with antibiotics and phenolic compounds synergistically inhibits C. jejuni by impacting both antimicrobial influx and efflux. PMID:26528273

  1. Active efflux of fluoroquinolones in Mycobacterium smegmatis mediated by LfrA, a multidrug efflux pump.

    PubMed Central

    Liu, J; Takiff, H E; Nikaido, H

    1996-01-01

    The lfrA gene cloned from chromosomal DNA of quinolone-resistant Mycobacterium smegmatis mc2-552 conferred low-level resistance to fluoroquinolones when present on multicopy plasmids. Sequence analysis suggested that lfrA encodes a membrane efflux pump of the major facilitator family (H. E. Takiff, M. Cimino, M. C. Musso, T. Weisbrod, R. Martinez, M. B. Delgado, L Salazar, B. R. Bloom, and W. R. Jacbos, Jr., Proc. Natl. Acad. Sci. USA 93:362-366, 1996). In this work, we studied the role of LfrA in the accumulation of fluoroquinolones by M. smegmatis. The steady-state accumulation level of a hydrophilic quinolone, norfloxacin, by M. smegmatis harboring a plasmid carrying the lfrA gene was about 50% of that by the parent strain but was increased to the same level as that of the parent strain by addition of a proton conductor, carbonyl cyanide m-chorophenylhydrazone. Norfloxacin efflux mediated by LfrA was competed for strongly by ciprofloxacin but not by nalidixic acid. Furthermore, we showed that portions of norfloxacin accumulated by starved cells were pumped out upon reenergization of the cells, and the rates of this efflux showed evidence of saturation at higher intracellular concentrations of the drug. These results suggest that the LfrA polypeptide catalyzes the active efflux of several quinolones. PMID:8682782

  2. Hidden Selection of Bacterial Resistance to Fluoroquinolones In Vivo: The Case of Legionella pneumophila and Humans

    PubMed Central

    Shadoud, Lubana; Almahmoud, Iyad; Jarraud, Sophie; Etienne, Jérôme; Larrat, Sylvie; Schwebel, Carole; Timsit, Jean-François; Schneider, Dominique; Maurin, Max

    2015-01-01

    Background Infectious diseases are the leading cause of human morbidity and mortality worldwide. One dramatic issue is the emergence of microbial resistance to antibiotics which is a major public health concern. Surprisingly however, such in vivo adaptive ability has not been reported yet for many intracellular human bacterial pathogens such as Legionella pneumophila. Methods We examined 82 unrelated patients with Legionnaire's disease from which 139 respiratory specimens were sampled during hospitalization and antibiotic therapy. We both developed a real time PCR assay and used deep-sequencing approaches to detect antibiotic resistance mutations in L. pneumophila and follow their selection and fate in these samples. Findings We identified the in vivo selection of fluoroquinolone resistance mutations in L. pneumophila in two infected patients treated with these antibiotics. By investigating the mutational dynamics in patients, we showed that antibiotic resistance occurred during hospitalization most likely after fluoroquinolone treatment. Interpretation In vivo selection of antibiotic resistances in L. pneumophila may be associated with treatment failures and poor prognosis. This hidden resistance must be carefully considered in the therapeutic management of legionellosis patients and in the control of the gradual loss of effectiveness of antibiotics. PMID:26501115

  3. Synergistic anti-Campylobacter jejuni activity of fluoroquinolone and macrolide antibiotics with phenolic compounds.

    PubMed

    Oh, Euna; Jeon, Byeonghwa

    2015-01-01

    The increasing resistance of Campylobacter to clinically important antibiotics, such as fluoroquinolones and macrolides, is a serious public health problem. The objective of this study is to investigate synergistic anti-Campylobacter jejuni activity of fluoroquinolones and macrolides in combination with phenolic compounds. Synergistic antimicrobial activity was measured by performing a checkerboard assay with ciprofloxacin and erythromycin in the presence of 21 phenolic compounds. Membrane permeability changes in C. jejuni by phenolic compounds were determined by measuring the level of intracellular uptake of 1-N-phenylnaphthylamine (NPN). Antibiotic accumulation assays were performed to evaluate the level of ciprofloxacin accumulation in C. jejuni. Six phenolic compounds, including p-coumaric acid, sinapic acid, caffeic acid, vanillic acid, gallic acid, and taxifolin, significantly increased the susceptibility to ciprofloxacin and erythromycin in several human and poultry isolates. The synergistic antimicrobial effect was also observed in ciprofloxacin- and erythromycin-resistant C. jejuni strains. The phenolic compounds also substantially increased membrane permeability and antibiotic accumulation in C. jejuni. Interestingly, some phenolic compounds, such as gallic acid and taxifolin, significantly reduced the expression of the CmeABC multidrug efflux pump. Phenolic compounds increased the NPN accumulation in the cmeB mutant, indicating phenolic compounds may affect the membrane permeability. In this study, we successfully demonstrated that combinational treatment of C. jejuni with antibiotics and phenolic compounds synergistically inhibits C. jejuni by impacting both antimicrobial influx and efflux.

  4. Quantification of Fluoroquinolone Uptake through the Outer Membrane Channel OmpF of Escherichia coli.

    PubMed

    Cama, Jehangir; Bajaj, Harsha; Pagliara, Stefano; Maier, Theresa; Braun, Yvonne; Winterhalter, Mathias; Keyser, Ulrich F

    2015-11-01

    Decreased drug accumulation is a common cause of antibiotic resistance in microorganisms. However, there are few reliable general techniques capable of quantifying drug uptake through bacterial membranes. We present a semiquantitative optofluidic assay for studying the uptake of autofluorescent drug molecules in single liposomes. We studied the effect of the Escherichia coli outer membrane channel OmpF on the accumulation of the fluoroquinolone antibiotic, norfloxacin, in proteoliposomes. Measurements were performed at pH 5 and pH 7, corresponding to two different charge states of norfloxacin that bacteria are likely to encounter in the human gastrointestinal tract. At both pH values, the porins significantly enhance drug permeation across the proteoliposome membranes. At pH 5, where norfloxacin permeability across pure phospholipid membranes is low, the porins increase drug permeability by 50-fold on average. We estimate a flux of about 10 norfloxacin molecules per second per OmpF trimer in the presence of a 1 mM concentration gradient of norfloxacin. We also performed single channel electrophysiology measurements and found that the application of transmembrane voltages causes an electric field driven uptake in addition to concentration driven diffusion. We use our results to propose a physical mechanism for the pH mediated change in bacterial susceptibility to fluoroquinolone antibiotics.

  5. Determination of residual fluoroquinolones in honey by liquid chromatography using metal chelate affinity chromatography.

    PubMed

    Yatsukawa, Yoh-Ichi; Ito, Hironobu; Matsuda, Takahiro; Nakamura, Munetomo; Watai, Masatoshi; Fujita, Kazuhiro

    2011-01-01

    A new analytical method for the simultaneous determination of seven fluoroquinolones, namely, norfloxacin, ciprofloxacin, danofloxacin, enrofloxacin, orbifloxacin, sarafloxacin, and difloxacin, especially in dark-colored honey, has been developed. Fluoroquinolone antibiotics were extracted from samples with MacIlvaine buffer solution (pH 4.0) containing EDTA disodium salt dihydrate. The extracts were treated with both a polymeric cartridge and a metal chelate affinity column preloaded with ferric ion (Fe3+). LC separation with fluorescence detection was performed at 40 degrees C using an Inertsil ODS-4 analytical column (150 x 4.6 mm, 3 microm). The mobile phase was composed of 20 mM/L citrate buffer solution (pH 3.1)-acetonitrile mixture (70 + 30, v/v) containing 1 mM/L sodium dodecyl sulfate. Lomefloxacin was used as an internal standard. The developed method was validated according to the criteria of European Commission Decision 2002/657/EC. Decision limits and detection capabilities were below 2.9 and 4.4 microg/kg, respectively.

  6. Sequential Acquisition of Virulence and Fluoroquinolone Resistance Has Shaped the Evolution of Escherichia coli ST131

    PubMed Central

    Alsheikh-Hussain, Areej S.; Ashcroft, Melinda M.; Khanh Nhu, Nguyen Thi; Roberts, Leah W.; Stanton-Cook, Mitchell

    2016-01-01

    ABSTRACT Escherichia coli ST131 is the most frequently isolated fluoroquinolone-resistant (FQR) E. coli clone worldwide and a major cause of urinary tract and bloodstream infections. Although originally identified through its association with the CTX-M-15 extended-spectrum β-lactamase resistance gene, global genomic epidemiology studies have failed to resolve the geographical and temporal origin of the ST131 ancestor. Here, we developed a framework for the reanalysis of publically available genomes from different countries and used this data set to reconstruct the evolutionary steps that led to the emergence of FQR ST131. Using Bayesian estimation, we show that point mutations in chromosomal genes that confer FQR coincide with the first clinical use of fluoroquinolone in 1986 and illustrate the impact of this pivotal event on the rapid population expansion of ST131 worldwide from an apparent origin in North America. Furthermore, we identify virulence factor acquisition events that predate the development of FQR, suggesting that the gain of virulence-associated genes followed by the tandem development of antibiotic resistance primed the successful global dissemination of ST131. PMID:27118589

  7. Degradation of two fluoroquinolone antibiotics photoinduced by Fe(III)-microalgae suspension in an aqueous solution.

    PubMed

    Ge, Liyun; Deng, Huanhuan

    2015-04-01

    The widespread presence of fluoroquinolone antibiotics (FQs) in natural ecosystems is a health hazard for humans and other living organisms. In this work, the photochemical degradation process of two antibiotics in the presence of Fe(III) and marine microalgae has been studied. Two fluoroquinolone (FQ) antibiotics, enrofloxacin (ENR) and ciprofloxacin hydrochloride (CIP), and two marine microalgae, Platymonas subcordiformis and Isochrysis galbana, were investigated under irradiation with a high-pressure mercury lamp (HPML) in a laboratory-scale experiment. The effects of the initial concentration of antibiotics on the degradation of these two FQs in Fe(III)-algae suspensions were also investigated. On the basis of the information in this study, compared to other systems, the efficiency of photo-degradation of the two FQs is better at lower FQ concentrations in the Fe(III)-algae system. Moreover, the low initial concentration of antibiotics benefits the photochemical process of antibiotics. This work demonstrated that the Fe(III)-algae system is an interesting and valuable research area and could be considered as a promising photochemical system for seawater remediation.

  8. Effects of β-Lactam Antibiotics and Fluoroquinolones on Human Gut Microbiota in Relation to Clostridium difficile Associated Diarrhea

    PubMed Central

    Heinsen, Femke Anouska; Knecht, Carolin; Schilhabel, Anke; Schmitz, Ruth A.; Zimmermann, Alexandra; dos Santos, Vitor Martins; Ferrer, Manuel; Rosenstiel, Philip C.; Schreiber, Stefan; Friedrichs, Anette K.; Ott, Stephan J.

    2014-01-01

    Clostridium difficile infections are an emerging health problem in the modern hospital environment. Severe alterations of the gut microbiome with loss of resistance to colonization against C. difficile are thought to be the major trigger, but there is no clear concept of how C. difficile infection evolves and which microbiological factors are involved. We sequenced 16S rRNA amplicons generated from DNA and RNA/cDNA of fecal samples from three groups of individuals by FLX technology: (i) healthy controls (no antibiotic therapy); (ii) individuals receiving antibiotic therapy (Ampicillin/Sulbactam, cephalosporins, and fluoroquinolones with subsequent development of C. difficile infection or (iii) individuals receiving antibiotic therapy without C. difficile infection. We compared the effects of the three different antibiotic classes on the intestinal microbiome and the effects of alterations of the gut microbiome on C. difficile infection at the DNA (total microbiota) and rRNA (potentially active) levels. A comparison of antibiotic classes showed significant differences at DNA level, but not at RNA level. Among individuals that developed or did not develop a C. difficile infection under antibiotics we found no significant differences. We identified single species that were up- or down regulated in individuals receiving antibiotics who developed the infection compared to non-infected individuals. We found no significant differences in the global composition of the transcriptionally active gut microbiome associated with C. difficile infections. We suggest that up- and down regulation of specific bacterial species may be involved in colonization resistance against C. difficile providing a potential therapeutic approach through specific manipulation of the intestinal microbiome. PMID:24586762

  9. Multiresidue analysis of fluoroquinolone antimicrobials in chicken meat by molecularly imprinted solid-phase extraction and high performance liquid chromatography.

    PubMed

    Urraca, J L; Castellari, M; Barrios, C A; Moreno-Bondi, M C

    2014-05-23

    This paper describes the synthesis of novel molecularly imprinted polymer (MIP) micro-beads for the selective extraction (MISPE) of six fluoroquinolone (FQ) antibiotics (enrofloxacin, ciprofloxacin, lomefloxacin, danofloxacin, sarafloxacin and norfloxacin) from chicken muscle samples and further analysis by high-performance liquid chromatography (HPLC) with fluorescence (FLD) or mass spectrometry (MS) detection. A combinatorial screening approach has been applied to select the optimal functional monomer and cross-linker formulation for polymer synthesis. The MIP prepared using enoxacin (ENOX) as the template - a mixture of methacrylic acid (MAA) and trifluoromethacrylic acid (TFMAA) as functional monomers and ethylene glycol dimethacrylate (EDMA) as the cross-linker - showed superior FQ recognition properties than the rest of the materials generated. MIP spherical particles were prepared using silica beads as sacrificial scaffolds. The polymers were packed in solid phase extraction (SPE) cartridges. The optimized MISPE-HPLC method allows the extraction of the antimicrobials from aqueous samples followed by a selective washing with acetonitrile/water (0.005% TFA, pH=3.0), 20:80 (v/v) and elution with 5% trifluoroacetic acid in methanol. Optimum MISPE conditions led to recoveries of the target FQs in chicken muscle samples ranging between 68 and 102% and precisions in the 3-4% range (RSD, n=18). The method has been validated according to European Union Decision 2002/657/EC, in terms of linearity, accuracy, precision, selectivity, decision limit (CCα) and detection capability (CCβ) by HPLC-FLD and HPLC-MS/MS. The limits of detection were improved using HPLC-MS/MS analysis and ranged between 0.2 and 2.7μgkg(-1) (S/N=3) for all the FQs tested.

  10. Consensus Report of the 4th International Forum for Gadolinium-Ethoxybenzyl-Diethylenetriamine Pentaacetic Acid Magnetic Resonance Imaging

    PubMed Central

    Zech, Christoph J; Bolondi, Luigi; Jonas, Eduard; Kim, Myeong-Jin; Matsui, Osamu; Merkle, Elmar M.; Sakamoto, Michiie; Choi, Byung Ihn

    2011-01-01

    This paper reports on issues relating to the optimal use of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid magnetic resonance imaging (Gd-EOB-DTPA MR imaging) together with the generation of consensus statements from a working group meeting, which was held in Seoul, Korea (2010). Gd-EOB-DTPA has been shown to improve the detection and characterization of liver lesions, and the information provided by the hepatobiliary phase is proving particularly useful in differential diagnoses and in the characterization of small lesions (around 1-1.5 cm). Discussion also focused on advances in the role of organic anion-transporting polypeptide 8 (OATP8) transporters. Gd-EOB-DTPA is also emerging as a promising tool for functional analysis, enabling the calculation of post-surgical liver function in the remaining segments. Updates to current algorithms were also discussed. PMID:21852900

  11. Risk Factors for Infection with Escherichia coli in Nursing Home Residents Colonized with Fluoroquinolone-Resistant E. coli

    PubMed Central

    Manning, Sara; Lautenbach, Ebbing; Tolomeo, Pam; Han, Jennifer H.

    2015-01-01

    A case-control study to determine risk factors for clinical infection with Escherichia coli was conducted among nursing home residents colonized with fluoroquinolone-resistant E. coli. Among 94 subjects, 11 (12%) developed infections with E. coli. Risk factors included the presence of a urinary catheter or tracheostomy, diabetes mellitus, and trimethoprim-sulfamethoxazole exposure. PMID:25880678

  12. Fluoroquinolones and qnr genes in sediment, water, soil, and human fecal flora in an environment polluted by manufacturing discharges.

    PubMed

    Rutgersson, Carolin; Fick, Jerker; Marathe, Nachiket; Kristiansson, Erik; Janzon, Anders; Angelin, Martin; Johansson, Anders; Shouche, Yogesh; Flach, Carl-Fredrik; Larsson, D G Joakim

    2014-07-15

    There is increasing concern that environmental antibiotic pollution promotes transfer of resistance genes to the human microbiota. Here, fluoroquinolone-polluted river sediment, well water, irrigated farmland, and human fecal flora of local villagers within a pharmaceutical industrial region in India were analyzed for quinolone resistance (qnr) genes by quantitative PCR. Similar samples from Indian villages farther away from industrial areas, as well as fecal samples from Swedish study participants and river sediment from Sweden, were included for comparison. Fluoroquinolones were detected by MS/MS in well water and soil from all villages located within three km from industrially polluted waterways. Quinolone resistance genes were detected in 42% of well water, 7% of soil samples and in 100% and 18% of Indian and Swedish river sediments, respectively. High antibiotic concentrations in Indian sediment coincided with high abundances of qnr, whereas lower fluoroquinolone levels in well water and soil did not. We could not find support for an enrichment of qnr in fecal samples from people living in the fluoroquinolone-contaminated villages. However, as qnr was detected in 91% of all Indian fecal samples (24% of the Swedish) it suggests that the spread of qnr between people is currently a dominating transmission route.

  13. A novel ciprofloxacin-resistant subclade of H58 Salmonella Typhi is associated with fluoroquinolone treatment failure

    PubMed Central

    Pham Thanh, Duy; Karkey, Abhilasha; Dongol, Sabina; Ho Thi, Nhan; Thompson, Corinne N; Rabaa, Maia A; Arjyal, Amit; Holt, Kathryn E; Wong, Vanessa; Tran Vu Thieu, Nga; Voong Vinh, Phat; Ha Thanh, Tuyen; Pradhan, Ashish; Shrestha, Saroj Kumar; Gajurel, Damoder; Pickard, Derek; Parry, Christopher M; Dougan, Gordon; Wolbers, Marcel; Dolecek, Christiane; Thwaites, Guy E; Basnyat, Buddha; Baker, Stephen

    2016-01-01

    The interplay between bacterial antimicrobial susceptibility, phylogenetics and patient outcome is poorly understood. During a typhoid clinical treatment trial in Nepal, we observed several treatment failures and isolated highly fluoroquinolone-resistant Salmonella Typhi (S. Typhi). Seventy-eight S. Typhi isolates were genome sequenced and clinical observations, treatment failures and fever clearance times (FCTs) were stratified by lineage. Most fluoroquinolone-resistant S. Typhi belonged to a specific H58 subclade. Treatment failure with S. Typhi-H58 was significantly less frequent with ceftriaxone (3/31; 9.7%) than gatifloxacin (15/34; 44.1%)(Hazard Ratio 0.19, p=0.002). Further, for gatifloxacin-treated patients, those infected with fluoroquinolone-resistant organisms had significantly higher median FCTs (8.2 days) than those infected with susceptible (2.96) or intermediately resistant organisms (4.01)(p<0.001). H58 is the dominant S. Typhi clade internationally, but there are no data regarding disease outcome with this organism. We report an emergent new subclade of S. Typhi-H58 that is associated with fluoroquinolone treatment failure. Clinical trial registration: ISRCTN63006567. DOI: http://dx.doi.org/10.7554/eLife.14003.001 PMID:26974227

  14. A novel ciprofloxacin-resistant subclade of H58 Salmonella Typhi is associated with fluoroquinolone treatment failure.

    PubMed

    Pham Thanh, Duy; Karkey, Abhilasha; Dongol, Sabina; Ho Thi, Nhan; Thompson, Corinne N; Rabaa, Maia A; Arjyal, Amit; Holt, Kathryn E; Wong, Vanessa; Tran Vu Thieu, Nga; Voong Vinh, Phat; Ha Thanh, Tuyen; Pradhan, Ashish; Shrestha, Saroj Kumar; Gajurel, Damoder; Pickard, Derek; Parry, Christopher M; Dougan, Gordon; Wolbers, Marcel; Dolecek, Christiane; Thwaites, Guy E; Basnyat, Buddha; Baker, Stephen

    2016-01-01

    The interplay between bacterial antimicrobial susceptibility, phylogenetics and patient outcome is poorly understood. During a typhoid clinical treatment trial in Nepal, we observed several treatment failures and isolated highly fluoroquinolone-resistant Salmonella Typhi (S. Typhi). Seventy-eight S. Typhi isolates were genome sequenced and clinical observations, treatment failures and fever clearance times (FCTs) were stratified by lineage. Most fluoroquinolone-resistant S. Typhi belonged to a specific H58 subclade. Treatment failure with S. Typhi-H58 was significantly less frequent with ceftriaxone (3/31; 9.7%) than gatifloxacin (15/34; 44.1%)(Hazard Ratio 0.19, p=0.002). Further, for gatifloxacin-treated patients, those infected with fluoroquinolone-resistant organisms had significantly higher median FCTs (8.2 days) than those infected with susceptible (2.96) or intermediately resistant organisms (4.01)(pS. Typhi clade internationally, but there are no data regarding disease outcome with this organism. We report an emergent new subclade of S. Typhi-H58 that is associated with fluoroquinolone treatment failure. PMID:26974227

  15. Rapid and sensitive detection of fluoroquinolone-resistant Escherichia coli from urine samples using a genotyping DNA microarray.

    PubMed

    Yu, Xiaolei; Susa, Milorad; Weile, Jan; Knabbe, Cornelius; Schmid, Rolf D; Bachmann, Till T

    2007-10-01

    Urinary tract infections (UTI) are among the most common bacterial infections in humans, with Escherichia coli being the major cause of infection. Fluoroquinolone resistance of uropathogenic E. coli has increased significantly over the last decade. In this study a microarray-based assay was developed and applied, which provides a rapid, sensitive and specific detection of fluoroquinolone-resistant E. coli in urine. The capture probes were designed against previously identified and described hotspots for quinolone resistance (codons 83 and 87 of gyrA). The key goals of this development were to reduce assay time while increasing the sensitivity and specificity as compared with a pilot version of a gyrA genotyping DNA microarray. The performance of the assay was demonstrated with pure cultures of 30 E. coli isolates as well as with urine samples spiked with 6 E. coli isolates. The microarray results were confirmed by standard DNA sequencing and were in full agreement with the phenotypic antimicrobial susceptibility testing using standard methods. The DNA microarray test displayed an assay time of 3.5h, a sensitivity of 100CFU/ml, and the ability to detect fluoroquinolone-resistant E. coli in the presence of a 10-fold excess of fluoroquinolone-susceptible E. coli cells. As a consequence, we believe that this microarray-based determination of antibiotics resistance has a true potential for the application in clinical routine laboratories in the future.

  16. Study on the interaction between fluoroquinolones and erythrosine by absorption, fluorescence and resonance Rayleigh scattering spectra and their application

    NASA Astrophysics Data System (ADS)

    Wang, Jian; Liu, Zhongfang; Liu, Jiangtao; Liu, Shaopu; Shen, Wei

    2008-03-01

    In pH 4.4-4.5 Britton-Robinson (BR) buffer solution, fluoroquinolone antibiotics (FLQs) including ciprofloxacin (CIP), norfloxacin (NOR), levofloxacin (LEV) and lomefloxacin (LOM) could react with erythrosine (Ery) to form 1:1 ion-association complexes, which not only resulted in the changes of the absorption spectra and the quenching of fluorescence, but also resulted in the great enhancement of resonance Rayleigh scattering (RRS). These offered some indications of the determination of fluoroquinolone antibiotics by spectrophotometric, fluorescence and resonance Rayleigh scattering methods. The detection limits for fluoroquinolone antibiotics were in the range of 0.097-0.265 μg/mL for absorption methods, 0.022-0.100 μg/mL for fluorophotometry and 0.014-0.027 μg/mL for RRS method, respectively. Among them, the RRS method had the highest sensitivity. In this work, the spectral characteristics of the absorption, fluorescence and RRS, the optimum conditions of the reactions and the properties of the analytical chemistry were investigated. The methods have been successfully applied to determination of some fluoroquinolone antibiotics in human urine samples and tablets. Taking CIP-Ery system as an example, the charge distribution, the enthalpy of formation and the mean polarizability were calculated by density function theory (DFT) method. In addition, the reasons for the enhancement of scattering spectra were discussed.

  17. International Symposium on Wind Energy Systems, 4th, Stockholm, Sweden, September 21-24, 1982, Proceedings. Volumes 1 & 2

    NASA Astrophysics Data System (ADS)

    Stephens, H. S.; Goodes, D. H.

    Progress in theoretical, meteorological, and hardware development sectors of wind energy utilization is assessed for various national programs. Wind regime characterization studies in Agentina, China, Indonesia, Norway, the U.S., Canada, Sweden, Hawaii, and offshore of the U.K. are reported. Data gained from wind turbine test sites in the U.S., Denmark, Holland, Germany, and the Netherlands are outlined. Attention is focused on the economics of wind turbine production for utility, agricultural, and third party purposes, with mention made of utilizing the resource appropriately for areas of installation of the wind powered machinery. Analyses are made of diurnal wind variations compared to diurnal demands on conventinal electricity generating power stations. Performance projections are made for wind farms featuring multi-MW machines, taking into account grid inteconnection factors, electrical control, power ramps, and environmental considerations. Mention is made of aeroelastics, dynamics, and the aerodynamics of wind turbines and rotor blades. Finally, icing, noise, fatigue failure, and blade throw problem are discussed, together with wind turbine licensing procedures in Denmark. No invidivual items are abstracted in these volumes

  18. The Effectiveness and Safety of Fluoroquinolone-Containing Regimen as a First-Line Treatment for Drug-Sensitive Pulmonary Tuberculosis: A Systematic Review and Meta-Analysis

    PubMed Central

    Lee, Hyun Woo; Lee, Jung Kyu; Kim, Eunyoung; Yim, Jae-Joon; Lee, Chang-Hoon

    2016-01-01

    Background Fluoroquinolone is recommended as a pivotal antituberculous agent for treating multi-drug-resistant pulmonary tuberculosis. However, its effectiveness as first-line treatment remains controversial. The present study was conducted to validate the fluoroquinolone-containing regimen for drug-sensitive pulmonary tuberculosis. Methods We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials until June 5, 2015. Randomized controlled trials (RCTs) that compared antituberculous regimens containing fluoroquinolone with the standard regimen were included. Results Eleven RCTs that included 6,334 patients were selected. Fluoroquinolone-containing regimens had a higher rate of sputum culture conversion at 2 months of treatment (M-H fixed odds ratio [OR], 1.36; 95% confidence interval [CI], 1.20–1.54). However, the outcomes were less favorable (M-H fixed OR, 0.69; 95% CI, 0.59–0.82) and the associated total adverse events were more frequent (M-H fixed OR, 1.84; 95% CI, 1.46–2.31) in the fluoroquinolone-containing regimen group, without a significant heterogeneity according to treatment duration. Treatment with the fluoroquinolone-containing regimen for 4 months showed a higher relapse rate. Conclusions Despite a higher culture conversion rate at 2 months of treatment, the fluoroquinolone-containing regimen had limitations, including less favorable outcomes and more adverse events, as the first-line therapy for drug-sensitive pulmonary tuberculosis. PMID:27455053

  19. Bactericidal/permeability-increasing protein (rBPI21) and fluoroquinolone mitigate radiation-induced bone marrow aplasia and death

    PubMed Central

    Guinan, Eva C.; Barbon, Christine M.; Kalish, Leslie A.; Parmar, Kalindi; Kutok, Jeff; Mancuso, Christy J.; Stoler-Barak, Liat; Suter, Eugénie E.; Russell, Janice D.; Palmer, Christine D.; Gallington, Leighanne C.; Voskertchian, Annie; Vergilio, Jo-Anne; Cole, Geoffrey; Zhu, Kaya; D’Andrea, Alan; Soiffer, Robert; Weiss, Jerrold P.; Levy, Ofer

    2014-01-01

    Identification of safe, effective treatment strategies to mitigate toxicity after extensive radiation exposure has proven challenging. Only a limited number of candidate approaches have emerged, and the Federal Drug Administration has yet to approve any agent for a mass-casualty radiation disaster indication. As preparative treatments for hematopoietic stem cell transplantation (HSCT) produce toxicities similar to such radiation exposures, we studied patients early after myeloablative HSCT to identify new approaches to this problem. Patients rapidly developed endotoxemia and reduced plasma bactericidal/permeability-increasing protein (BPI), a potent endotoxin-neutralizing protein, in association with neutropenia. We hypothesized that a treatment supplying similar endotoxin-neutralizing activity might replace the BPI deficit and mitigate radiation toxicity. We tested this idea in mice. A single 7 Gy radiation dose, which was 95% lethal by 30 days, was followed 24 hours later by twice daily subcutaneous injections of the recombinant BPI fragment rBPI21 or vehicle alone for 14 or 30 days, with or without an oral fluoroquinolone antibiotic with broad-spectrum anti-bacterial activity including that against endotoxin-bearing Gram-negative bacteria. Compared to either fluoroquinolone alone or vehicle/fluoroquinolone, combined rBPI21/fluoroquinolone treatment improved survival, accelerated hematopoietic recovery and promoted expansion of stem and progenitor cells. The observed efficacy of rBPI21 and fluoroquinolones initiated 24 hours after lethal irradiation, combined with their favorable bioactivity and safety profiles in critically-ill humans, suggest the potential clinical utility of this radiation mitigation strategy and support its further evaluation. PMID:22116933

  20. Molecularly imprinted pipette-tip solid phase extraction for selective determination of fluoroquinolones in human urine using HPLC-DAD.

    PubMed

    de Oliveira, Hanna Leijoto; da Silva Anacleto, Sara; da Silva, Anny Talita Maria; Pereira, Arnaldo César; de Souza Borges, Warley; Figueiredo, Eduardo Costa; Borges, Keyller Bastos

    2016-10-15

    A simple method using HPLC-DAD was developed for the determination of fluoroquinolones in human urine including ciprofloxacin (CIPRO), enrofloxacino (ENRO), marbofloxacino (MARBO) and norfloxacin (NOR). In addition, it was studied the extraction of fluoroquinolones in human urine samples using pipette tip-based molecularly imprinted polymers solid phase extraction (PT-MIPs-SPE). With the goal of finding the best procedure for extraction of four fluoroquinolones in human urine, several parameters that are likely to affect the efficiency of extraction during sample preparation, including the washing solvent, type and volume of eluent, amount of material, the volume of the sample, pH and the ionic strength were systematically optimized. Chromatographic separations of fluoroquinolones were hit within 10min using a Synergi(®) C18 (250×4.6mm, 4μm) column and mobile phase consisting of water (10mM of phosphoric acid, the pH adjusted at 3.29 with triethylamine) : acetonitrile (85.7: 14.3, v/v) at a flow rate of 1.5mLmin(-1). Detection was performed at 290nm. The average extraction recoveries/standard deviation relative to ENRO, CIPRO, NOR and MARBO were 96.40±5.51%, 42.47±4.81%, 41.82±7.99% and 87.49±4.70, respectively. The method was liner from 39 to 1260ngmL(-1) for each fluoroquinolone with correlation coefficient of 0.9904, 0.9910, 0.9914 and 0.9919, to ENRO, CIPRO, NOR and MARBO, respectively. The assays of within-day and between-day precision and accuracy for all analytes were studied at three concentration levels and were lower than 15%. The method was successfully employed in a preliminary cumulative urinary excretion study after administration of CIPRO to a healthy volunteer.

  1. Development of a Pefloxacin Disk Diffusion Method for Detection of Fluoroquinolone-Resistant Salmonella enterica

    PubMed Central

    Matuschek, Erika; Sjölund-Karlsson, Maria; Åhman, Jenny; Petersen, Andreas; Stegger, Marc; Torpdahl, Mia; Kahlmeter, Gunnar

    2015-01-01

    Fluoroquinolones (FQs) are among the drugs of choice for treatment of Salmonella infections. However, fluoroquinolone resistance is increasing in Salmonella due to chromosomal mutations in the quinolone resistance-determining regions (QRDRs) of the topoisomerase genes gyrA, gyrB, parC, and parE and/or plasmid-mediated quinolone resistance (PMQR) mechanisms including qnr variants, aac(6′)-Ib-cr, qepA, and oqxAB. Some of these mutations cause only subtle increases in the MIC, i.e., MICs ranging from 0.12 to 0.25 mg/liter for ciprofloxacin (just above the wild-type MIC of ≤0.06 mg/liter). These isolates are difficult to detect with standard ciprofloxacin disk diffusion, and plasmid-mediated resistance, such as qnr, is often not detected by the nalidixic acid screen test. We evaluated 16 quinolone/fluoroquinolone disks for their ability to detect low-level-resistant Salmonella enterica isolates that are not serotype Typhi. A total of 153 Salmonella isolates characterized for the presence (n = 104) or absence (n = 49) of gyrA and/or parC topoisomerase mutations, qnrA, qnrB, qnrD, qnrS, aac(6′)-Ib-cr, or qepA genes were investigated. All isolates were MIC tested by broth microdilution against ciprofloxacin, levofloxacin, and ofloxacin and by disk diffusion using EUCAST or CLSI methodology. MIC determination correctly categorized all isolates as either wild-type isolates (MIC of ≤0.06 mg/liter and absence of resistance genes) or non-wild-type isolates (MIC of >0.06 mg/liter and presence of a resistance gene). Disk diffusion using these antibiotics and nalidixic acid failed to detect some low-level-resistant isolates, whereas the 5-μg pefloxacin disk correctly identified all resistant isolates. However, pefloxacin will not detect isolates having aac(6′)-Ib-cr as the only resistance determinant. The pefloxacin disk assay was approved and implemented by EUCAST (in 2014) and CLSI (in 2015). PMID:26292292

  2. Stimulated electromagnetic emission and plasma line during pump wave frequency stepping near 4th electron gyroharmonic at HAARP

    NASA Astrophysics Data System (ADS)

    Grach, Savely; Sergeev, Evgeny; Shindin, Alexey; Mishin, Evgeny; Watkins, Brenton

    < f^* and mainly from altitudes h where f_0 <4f_c. The height h decreased with increasing f_0 in accordance with the altitude dependence 4f_c(h), the difference Delta f_g = f_0 - 4f_c was kept constant during either sweeping up [-(4-8 kHz)] or sweeping down [-(18-22 kHz)]. This corresponds to the difference between the altitude where f_0=4f_c and the PL generation altitude by Delta h sim 1.5-3 km and 7-8 km, respectively. During stepping up, the PL was observed also from the ranges where f_0 > 4f_c. In this case we obtained Delta f_g sim 8-13 kHz corresponding to Delta h sim - 4 km. The PL has never been observed for f_0>f^*$. \\ 1. Sergeev E., Grach S., et al. //Phys. Rev. Lett., 110 (2013), 065002.

  3. Climatic changes and social transformations in the Near East and North Africa during the 'long' 4th millennium BC: A comparative study of environmental and archaeological evidence

    NASA Astrophysics Data System (ADS)

    Clarke, Joanne; Brooks, Nick; Banning, Edward B.; Bar-Matthews, Miryam; Campbell, Stuart; Clare, Lee; Cremaschi, Mauro; di Lernia, Savino; Drake, Nick; Gallinaro, Marina; Manning, Sturt; Nicoll, Kathleen; Philip, Graham; Rosen, Steve; Schoop, Ulf-Dietrich; Tafuri, Mary Anne; Weninger, Bernhard; Zerboni, Andrea

    2016-03-01

    This paper explores the possible links between rapid climate change (RCC) and social change in the Near East and surrounding regions (Anatolia, central Syria, southern Israel, Mesopotamia, Cyprus and eastern and central Sahara) during the 'long' 4th millennium (∼4500-3000) BC. Twenty terrestrial and 20 marine climate proxies are used to identify long-term trends in humidity involving transitions from humid to arid conditions and vice versa. The frequency distribution of episodes of relative aridity across these records is calculated for the period 6300-2000 BC, so that the results may be interpreted in the context of the established arid episodes associated with RCC around 6200 and 2200 BC (the 8.2 and 4.2 kyr events). We identify two distinct episodes of heightened aridity in the early-mid 4th, and late 4th millennium BC. These episodes cluster strongly at 3600-3700 and 3100-3300 BC. There is also evidence of localised aridity spikes in the 5th and 6th millennia BC. These results are used as context for the interpretation of regional and local archaeological records with a particular focus on case studies from western Syria, the middle Euphrates, southern Israel and Cyprus. Interpretation of the records involves the construction of plausible narratives of human-climate interaction informed by concepts of adaptation and resilience from the literature on contemporary (i.e. 21st century) climate change and adaptation. The results are presented alongside well-documented examples of climatically-influenced societal change in the central and eastern Sahara, where detailed geomorphological studies of ancient environments have been undertaken in tandem with archaeological research. While the narratives for the Near East and Eastern Mediterranean remain somewhat speculative, the use of resilience and adaptation frameworks allows for a more nuanced treatment of human-climate interactions and recognises the diversity and context-specificity of human responses to climatic

  4. Impact of fluoroquinolones on human microbiota. Focus on the emergence of antibiotic resistance.

    PubMed

    de Lastours, Victoire; Fantin, Bruno

    2015-01-01

    The aggregate of microorganisms residing on the surface of the skin, in the oropharynx and in the GI tract, known as the human microbiota, play a major role as natural reservoirs for bacterial resistance to antibiotics. Fluoroquinolones (FQ) are among the most prescribed antibiotics and a major increase in FQ resistance is occurring worldwide. High concentrations of FQ are found in microbial ecosystems explaining their profound effect on the clinically relevant bacteria that compose them. Yet, because of different local pharmacokinetics, distinct selective pressures occur in the different microbiota. Here we review the qualitative and quantitative impact of FQ on the three main human microbiota and their consequences, particularly in terms of emergence of antibiotic resistance. Finally, we review potential actions that could decrease the impact of FQs on microbiota.

  5. Environmental photochemistry of fluoroquinolones in soil and in aqueous soil suspensions under solar light.

    PubMed

    Sturini, Michela; Speltini, Andrea; Maraschi, Federica; Pretali, Luca; Profumo, Antonella; Fasani, Elisa; Albini, Angelo

    2014-12-01

    The photodegradation fate of widely used fluoroquinolone (FQ) drugs has been studied both at the water-soil interface and in soil at actual concentrations (500 ng g(-1)) under natural solar light. Both human and veterinary drugs have been examined, namely ciprofloxacin, danofloxacin, enrofloxacin, levofloxacin, marbofloxacin and moxifloxacin. After spiking and irradiation, samples were submitted to microwave-assisted extraction and analyzed by high-performance liquid chromatography coupled to fluorescence detection (HPLC-FD). FQs degradation was faster in aqueous soil suspension than in neat soil (but lower than in "clean" water). A number of byproducts were identified by HPLC electrospray ionization tandem mass spectrometry after a post-extraction cleanup based on a molecularly imprinted polymer phase, for a more accurate detection. The distribution in the suspension was intermediate between those observed in soils and in aqueous solutions.

  6. Fluoroquinolone-resistant Escherichia coli carriage in long-term care facility.

    PubMed

    Maslow, Joel N; Lee, Betsy; Lautenbach, Ebbing

    2005-06-01

    We conducted a cross-sectional study to determine the prevalence of, and risk factors for, colonization with fluoroquinolone (FQ)-resistant Escherichia coli in residents in a long-term care facility. FQ-resistant E. coli were identified from rectal swabs for 25 (51%) of 49 participants at study entry. On multivariable analyses, prior FQ use was the only independent risk factor for FQ-resistant E. coli carriage and was consistent for FQ exposures in the previous 3, 6, 9, or 12 months. Pulsed-field gel electrophoresis of FQ-resistant E. coli identified clonal spread of 1 strain among 16 residents. Loss (6 residents) or acquisition (7 residents) of FQ-resistant E. coli was documented and was associated with de novo colonization with genetically distinct strains. Unlike the case in the hospital setting, FQ-resistant E. coli carriage in long-term care facilities is associated with clonal spread. PMID:15963284

  7. Spectrometric studies on the interaction of fluoroquinolones and bovine serum albumin

    NASA Astrophysics Data System (ADS)

    Ni, Yongnian; Su, Shaojing; Kokot, Serge

    2010-02-01

    The interaction between fluoroquinolones (FQs), ofloxacin and enrofloxacin, and bovine serum albumin (BSA) was investigated by fluorescence and UV-vis spectroscopy. It was demonstrated that the fluorescence quenching of BSA by FQ is a result of the formation of the FQ-BSA complex stabilized, in the main, by hydrogen bonds and van der Waals forces. The Stern-Volmer quenching constant, KSV, and the corresponding thermodynamic parameters, Δ H, Δ S and Δ G, were estimated. The distance, r, between the donor, BSA, and the acceptor, FQ, was estimated from fluorescence resonance energy transfer (FRET). The effect of FQ on the conformation of BSA was analyzed with the aid of UV-vis absorbance spectra and synchronous fluorescence spectroscopy. Spectral analysis showed that the two FQs affected the conformation of the BSA but in a different manner. Thus, with ofloxacin, the polarity around the tryptophan residues decreased and the hydrophobicity increased, while for enrofloxacin, the opposite effect was observed.

  8. Novel organic salts based on fluoroquinolone drugs: synthesis, bioavailability and toxicological profiles.

    PubMed

    Florindo, Catarina; Costa, Alexandra; Matos, Carla; Nunes, Sara L; Matias, Ana N; Duarte, Catarina M M; Rebelo, Luís Paulo N; Branco, Luís C; Marrucho, Isabel M

    2014-07-20

    In order to overcome the problems associated with low water solubility, and consequently low bioavailability of active pharmaceutical ingredients (APIs), novel organic salts containing fluoroquinolones (e.g. ciprofloxacin and norfloxacin) were prepared, using an optimized synthetic procedure based on direct protonation, with different biocompatible counter ions such as mesylate, gluconate and glycolate. All the prepared organic salts were characterized by spectroscopic techniques, mass spectrometry and thermal analysis. Solubility studies in water and simulated biological fluids at 25°C and 37°C were also performed. Additionally, octanol-water and phospholipid-water partition coefficients were measured at 25°C. The cytotoxicity and anti-inflammatory efficacy using an human cell model of intestinal epithelia (Caco-2 cells) were also evaluated and compared to those of the parent APIs. The adequate selection of the biocompatible anions allows the tuning of important physical, thermal and toxicological properties.

  9. Reduced fluoroquinolone susceptibility in Salmonella enterica serotypes in travelers returning from Southeast Asia.

    PubMed Central

    Hakanen, A.; Kotilainen, P.; Huovinen, P.; Helenius, H.; Siitonen, A.

    2001-01-01

    During 1995 to 1999, we collected 1,210 Salmonella isolates; 629 were from Finnish travelers returning from abroad. These isolates were tested for susceptibility by determining MICs to ciprofloxacin, nalidixic acid, and seven additional antimicrobial agents. From 1995 to 1999, the annual proportion of reduced ciprofloxacin susceptibility (MIC > 0.125 microg/mL) among all travelers' isolates increased from 3.9% to 23.5% (p<0.001). The increasing trend was outstanding among the isolates from Southeast Asia; isolates from Thailand alone increased from 5.6% to 50.0% (p<0.001). The reduced fluoroquinolone susceptibility was nonclonal in character and significantly associated with multidrug resistance. A point mutation in the quinolone resistance-determining region of gyrA was present in all isolates with reduced susceptibility. These data provide further evidence for the rapid spread of multidrug-resistant pathogens from one continent to another. PMID:11747728

  10. Simultaneous assay of fluoroquinolones and theophylline in plasma by high-performance liquid chromatography.

    PubMed

    Davis, J D; Aarons, L; Houston, J B

    1993-11-17

    A sensitive and selective reversed-phase high-performance liquid chromatographic method for the determination of theophylline in plasma simultaneously with either ciprofloxacin, enoxacin or norfloxacin has been developed. It involves extraction of plasma with chloroform-isopropanol or dichloromethane-isopropanol prior to chromatography on a Spherisorb ODS2 column. The mobile phase is 15% acetonitrile in a phosphate buffer (pH 3.0) containing tetrabutylammonium hydrogen sulphate (4.4 mM) as an ion-pairing agent. Ultraviolet detection is carried out at 280 nm. Run time is less than 10 min for all three separations. The assays have been used to determine the effect of plasma concentrations of fluoroquinolone on theophylline clearance.

  11. Development of a low-noise, 4th-order readout ASIC for CdZnTe detectors in gamma spectrometer applications

    NASA Astrophysics Data System (ADS)

    Wang, Jia; Su, Lin; Wei, Xiaomin; Zheng, Ran; Hu, Yann

    2016-09-01

    This paper presents an ASIC readout circuit development, which aims to achieve low noise. In order to compensate the leakage current and improve gain, a dual-stage CSA has been utilized. A 4th-order high-linearity shaper is proposed to obtain a Semi-Gaussian wave and further decrease the noise induced by the leakage current. The ASIC has been designed and fabricated in a standard commercial 2P4M 0.35 μm CMOS process. Die area of one channel is about 1190 μm×147 μm. The input charge range is 1.8 fC. The peaking time can be adjusted from 1 μs to 3 μs. Measured ENC is about 55e- (rms) at input capacitor of 0 F. The gain is 271 mV/fC at the peaking time of 1 μs.

  12. Computational modes and the Machenauer N.L.N.M.I. of the GLAS 4th order model. [NonLinear Normal Mode Initialization in numerical weather forecasting

    NASA Technical Reports Server (NTRS)

    Navon, I. M.; Bloom, S.; Takacs, L. L.

    1985-01-01

    An attempt was made to use the GLAS global 4th order shallow water equations to perform a Machenhauer nonlinear normal mode initialization (NLNMI) for the external vertical mode. A new algorithm was defined for identifying and filtering out computational modes which affect the convergence of the Machenhauer iterative procedure. The computational modes and zonal waves were linearly initialized and gravitational modes were nonlinearly initialized. The Machenhauer NLNMI was insensitive to the absence of high zonal wave numbers. The effects of the Machenhauer scheme were evaluated by performing 24 hr integrations with nondissipative and dissipative explicit time integration models. The NLNMI was found to be inferior to the Rasch (1984) pseudo-secant technique for obtaining convergence when the time scales of nonlinear forcing were much smaller than the time scales expected from the natural frequency of the mode.

  13. THE 4th SCHIZOPHRENIA INTERNATIONAL RESEARCH SOCIETY CONFERENCE, 5–9 APRIL 2014, FLORENCE, ITALY: A summary of topics and trends

    PubMed Central

    Abayomi, Olukayode; Amato, Davide; Bailey, Candace; Bitanihirwe, Byron; Bowen, Lynneice; Burshtein, Shimon; Cullen, Alexis; Fusté, Montserrat; Herrmann, Ana P; Khodaie, Babak; Kilian, Sanja; Lang, Qortni A; Manning, Elizabeth E; Massuda, Raffael; Nurjono, Milawaty; Sadiq, Sarosh; Sanchez-Gutierrez, Teresa; Sheinbaum, Tamara; Shivakumar, Venkataram; Simon, Nicholas; Spiteri-Staines, Anneliese; Sirijit, Suttajit; Toftdahl, Nanna Gilliam; Wadehra, Sunali; Wang, Yi; Wigton, Rebekah; Wright, Susan; Yagoda, Sergey; Zaytseva, Yuliya; O’Shea, Anne; DeLisi, Lynn E.

    2015-01-01

    The 4th Schizophrenia International Research Society Conference was held in Florence, Italy, April 5–9, 2014.and this year had as its emphasis, “Fostering Collaboration in Schizophrenia Research”. Student travel awardees served as rapporteurs for each oral session, summarized the important contributions of each session and then each report was integrated into a final summary of data discussed at the entire conference by topic. It is hoped that by combining data from different presentations, patterns of interest will emerge and thus lead to new progress for the future. In addition, the following report provides an overview of the conference for those who were present, but could not participate in all sessions, and those who did not have the opportunity to attend, but who would be interested in an update on current investigations ongoing in the field of schizophrenia research. PMID:25306204

  14. The 4th Schizophrenia International Research Society Conference, 5-9 April 2014, Florence, Italy: a summary of topics and trends.

    PubMed

    Abayomi, Olukayode; Amato, Davide; Bailey, Candace; Bitanihirwe, Byron; Bowen, Lynneice; Burshtein, Shimon; Cullen, Alexis; Fusté, Montserrat; Herrmann, Ana P; Khodaie, Babak; Kilian, Sanja; Lang, Qortni A; Manning, Elizabeth E; Massuda, Raffael; Nurjono, Milawaty; Sadiq, Sarosh; Sanchez-Gutierrez, Teresa; Sheinbaum, Tamara; Shivakumar, Venkataram; Simon, Nicholas; Spiteri-Staines, Anneliese; Sirijit, Suttajit; Toftdahl, Nanna Gilliam; Wadehra, Sunali; Wang, Yi; Wigton, Rebekah; Wright, Susan; Yagoda, Sergey; Zaytseva, Yuliya; O'Shea, Anne; DeLisi, Lynn E

    2014-11-01

    The 4th Schizophrenia International Research Society Conference was held in Florence, Italy, April 5-9, 2014 and this year had as its emphasis, "Fostering Collaboration in Schizophrenia Research". Student travel awardees served as rapporteurs for each oral session, summarized the important contributions of each session and then each report was integrated into a final summary of data discussed at the entire conference by topic. It is hoped that by combining data from different presentations, patterns of interest will emerge and thus lead to new progress for the future. In addition, the following report provides an overview of the conference for those who were present, but could not participate in all sessions, and those who did not have the opportunity to attend, but who would be interested in an update on current investigations ongoing in the field of schizophrenia research.

  15. Electrochemical oxidation of fluoroquinolone antibiotics: Mechanism, residual antibacterial activity and toxicity change.

    PubMed

    Zhu, Linyan; Santiago-Schübel, Beatrix; Xiao, Hongxia; Hollert, Henner; Kueppers, Stephan

    2016-10-01

    In this paper, we studied the electrochemical oxidation mechanisms of three typical fluoroquinolone antibiotics (FQs), and investigated residual antibacterial activity and toxicity changes after oxidation processes. Electrochemistry coupled to mass spectrometry (EC-MS) was used to study the oxidation processes of ciprofloxacin (CIP), norfloxacin (NOR) and ofloxacin (OFL). Eight oxidation products for each parent compound were identified and their chemical structures were elucidated. The transformation trend of each product, with the continuous increase of voltage from 0 to 3000 mV, was recorded by online EC-MS. The oxidation pathways were proposed based on the structural information and transformation trends of oxidation products. We found the oxidation mechanisms of FQs consisted of the hydroxylation and cleavage of piperazinyl ring via reactions with hydroxyl radicals, while the fluoroquinolone core remained intact. The antibacterial activity of the parent compounds and their oxidation mixtures was estimated using zone inhibition tests for gram-negative bacteria Salmonella typhimurium. It was found that the oxidation mixtures of CIP and NOR retained the antibacterial properties with lower activity compared to their parent compounds, while the antibacterial activity of OFL was almost eliminated after oxidation. Furthermore, the toxicity of the three FQs and their oxidation mixtures were evaluated using algal growth inhibition test (Desmodesmus subspicatus). The median effective concentration (EC50) values for the algal inhibition tests were calculated for the end point of growth rate. The toxicity of CIP and NOR to green algae after electrochemical oxidation, remained unchanged, while that of OFL significantly increased. The results presented in this paper contribute to an understanding of the electrochemical oxidation mechanisms of FQs, and highlight the potential environmental risks of FQs after electrochemical oxidation processes.

  16. Electrochemical oxidation of fluoroquinolone antibiotics: Mechanism, residual antibacterial activity and toxicity change.

    PubMed

    Zhu, Linyan; Santiago-Schübel, Beatrix; Xiao, Hongxia; Hollert, Henner; Kueppers, Stephan

    2016-10-01

    In this paper, we studied the electrochemical oxidation mechanisms of three typical fluoroquinolone antibiotics (FQs), and investigated residual antibacterial activity and toxicity changes after oxidation processes. Electrochemistry coupled to mass spectrometry (EC-MS) was used to study the oxidation processes of ciprofloxacin (CIP), norfloxacin (NOR) and ofloxacin (OFL). Eight oxidation products for each parent compound were identified and their chemical structures were elucidated. The transformation trend of each product, with the continuous increase of voltage from 0 to 3000 mV, was recorded by online EC-MS. The oxidation pathways were proposed based on the structural information and transformation trends of oxidation products. We found the oxidation mechanisms of FQs consisted of the hydroxylation and cleavage of piperazinyl ring via reactions with hydroxyl radicals, while the fluoroquinolone core remained intact. The antibacterial activity of the parent compounds and their oxidation mixtures was estimated using zone inhibition tests for gram-negative bacteria Salmonella typhimurium. It was found that the oxidation mixtures of CIP and NOR retained the antibacterial properties with lower activity compared to their parent compounds, while the antibacterial activity of OFL was almost eliminated after oxidation. Furthermore, the toxicity of the three FQs and their oxidation mixtures were evaluated using algal growth inhibition test (Desmodesmus subspicatus). The median effective concentration (EC50) values for the algal inhibition tests were calculated for the end point of growth rate. The toxicity of CIP and NOR to green algae after electrochemical oxidation, remained unchanged, while that of OFL significantly increased. The results presented in this paper contribute to an understanding of the electrochemical oxidation mechanisms of FQs, and highlight the potential environmental risks of FQs after electrochemical oxidation processes. PMID:27318447

  17. Residues of fluoroquinolones in marine aquaculture environment of the Pearl River Delta, South China.

    PubMed

    He, Xiuting; Wang, Zhaohui; Nie, Xiangping; Yang, Yufen; Pan, Debo; Leung, Anna O W; Cheng, Zhang; Yang, Yongtao; Li, Kaibin; Chen, Kunci

    2012-06-01

    Concentrations and distributions of selected fluoroquinolones (norfloxacin, ciprofloxacin and enrofloxacin) in water, sediments and nine kinds of fish species collected from 6 sites in two marine aquaculture regions of the Pearl River Delta, China, were analyzed by using high-performance liquid chromatography with fluorescence detector (HPLC). The results showed that the concentrations of ciprofloxacin and enrofloxacin were below the limits of quantification (LOQ) in all water samples except for norfloxacin. Norfloxacin and ciprofloxacin concentrations ranged from 1.88 to 11.20 ng g(-1) dry wt, 0.76-2.42 ng g(-1) dry wt in sediments collected from the Dapeng'ao region (sites 1-3) and ranged from 2.31 to 4.75 ng g(-1) dry wt, 1.26-1.76 ng g(-1) dry wt in sediments collected from the Hailing Island region (sites 4-6), respectively. However, no enrofloxacin was found in all sediment samples. The three fluoroquinolones (FQs) were detected in all fish samples, and the concentrations were higher in liver tissues than those in muscle tissues. The levels of norfloxacin were higher than ciprofloxacin and enrofloxacin in both liver and muscle tissues. Among the nine marine fish species, Siganus fuscescens from Hailing Island had a significantly high level of norfloxacin in liver tissue (254.58 ng g(-1) wet wt), followed by Sparus macrocephalus (133.15 ng g(-1) wet wt) from Dapeng'ao, and the lowest value was Lutianus argentimaculatus (5.18 ng g(-1) wet wt) from Hailing Island. The obtained results of FQs in present study do not represent a risk to the human health in Guangdong coastal area, based on the maximum residue limits (MRLs) established by Chinese Government and the acceptable daily intake (ADI) recommended by the Food and Agriculture Organization and World Health Organization (FAO/WHO).

  18. Reactive Oxygen Species Contribute to the Bactericidal Effects of the Fluoroquinolone Moxifloxacin in Streptococcus pneumoniae

    PubMed Central

    Ferrándiz, M. J.; Martín-Galiano, A. J.; Arnanz, C.; Zimmerman, T.

    2015-01-01

    We studied the transcriptomic response of Streptococcus pneumoniae to the fluoroquinolone moxifloxacin at a concentration that inhibits DNA gyrase. Treatment of the wild-type strain R6, at a concentration of 10× the MIC, triggered a response involving 132 genes after 30 min of treatment. Genes from several metabolic pathways involved in the production of pyruvate were upregulated. These included 3 glycolytic enzymes, which ultimately convert fructose 6-phosphate to pyruvate, and 2 enzymes that funnel phosphate sugars into the glycolytic pathway. In addition, acetyl coenzyme A (acetyl-CoA) carboxylase was downregulated, likely leading to an increase in acetyl-CoA. When coupled with an upregulation in formate acetyltransferase, an increase in acetyl-CoA would raise the production of pyruvate. Since pyruvate is converted by pyruvate oxidase (SpxB) into hydrogen peroxide (H2O2), an increase in pyruvate would augment intracellular H2O2. Here, we confirm a 21-fold increase in the production of H2O2 and a 55-fold increase in the amount of hydroxyl radical in cultures treated during 4 h with moxifloxacin. This increase in hydroxyl radical through the Fenton reaction would damage DNA, lipids, and proteins. These reactive oxygen species contributed to the lethality of the drug, a conclusion supported by the observed protective effects of an SpxB deletion. These results support the model whereby fluoroquinolones cause redox alterations. The transcriptional response of S. pneumoniae to moxifloxacin is compared with the response to levofloxacin, an inhibitor of topoisomerase IV. Levofloxacin triggers the transcriptional activation of iron transport genes and also enhances the Fenton reaction. PMID:26525786

  19. Phase 2 clinical trial of rapamycin-resistant donor CD4+ Th2/Th1 (T-Rapa) cells after low-intensity allogeneic hematopoietic cell transplantation

    PubMed Central

    Fowler, Daniel H.; Mossoba, Miriam E.; Steinberg, Seth M.; Halverson, David C.; Stroncek, David; Khuu, Hahn M.; Hakim, Frances T.; Castiello, Luciano; Sabatino, Marianna; Leitman, Susan F.; Mariotti, Jacopo; Gea-Banacloche, Juan C.; Sportes, Claude; Hardy, Nancy M.; Hickstein, Dennis D.; Pavletic, Steven Z.; Rowley, Scott; Goy, Andre; Donato, Michele; Korngold, Robert; Pecora, Andrew; Levine, Bruce L.; June, Carl H.; Gress, Ronald E.; Bishop, Michael R.

    2013-01-01

    In experimental models, ex vivo induced T-cell rapamycin resistance occurred independent of T helper 1 (Th1)/T helper 2 (Th2) differentiation and yielded allogeneic CD4+ T cells of increased in vivo efficacy that facilitated engraftment and permitted graft-versus-tumor effects while minimizing graft-versus-host disease (GVHD). To translate these findings, we performed a phase 2 multicenter clinical trial of rapamycin-resistant donor CD4+ Th2/Th1 (T-Rapa) cells after allogeneic-matched sibling donor hematopoietic cell transplantation (HCT) for therapy of refractory hematologic malignancy. T-Rapa cell products, which expressed a balanced Th2/Th1 phenotype, were administered as a preemptive donor lymphocyte infusion at day 14 post-HCT. After T-Rapa cell infusion, mixed donor/host chimerism rapidly converted, and there was preferential immune reconstitution with donor CD4+ Th2 and Th1 cells relative to regulatory T cells and CD8+ T cells. The cumulative incidence probability of acute GVHD was 20% and 40% at days 100 and 180 post-HCT, respectively. There was no transplant-related mortality. Eighteen of 40 patients (45%) remain in sustained complete remission (range of follow-up: 42-84 months). These results demonstrate the safety of this low-intensity transplant approach and the feasibility of subsequent randomized studies to compare T-Rapa cell-based therapy with standard transplantation regimens. This trial was registered at www.cancer.gov/clinicaltrials as #NCT 00077480. PMID:23426943

  20. Limbic system development underlies the emergence of classical fear conditioning during the 3rd and 4th weeks of life in the rat

    PubMed Central

    Deal, Alex L.; Erickson, Kristen J.; Shiers, Stephanie I.; Burman, Michael A.

    2016-01-01

    Classical fear conditioning creates an association between an aversive stimulus and a neutral stimulus. Although the requisite neural circuitry is well understood in mature organisms, the development of these circuits is less well studied. The current experiments examine the ontogeny of fear conditioning and relate it to neuronal activation assessed through immediate early gene (IEG) expression in the amygdala, hippocampus, perirhinal cortex, and hypothalamus of periweanling rats. Rat pups were fear conditioned, or not, during the 3rd or 4th weeks of life. Neuronal activation was assessed by quantifying expression of FBJ osteosarcoma oncogene (FOS) using immunohistochemistry (IHC) in Experiment 1. Fos and early growth response gene-1 (EGR1) expression was assessed using qRT-PCR in Experiment 2. Behavioral data confirm that both auditory and contextual fear continue to emerge between PD 17 and 24. The IEG expression data are highly consistent with these behavioral results. IHC results demonstrate significantly more FOS protein expression in the basal amygdala of fear conditioned PD 23 subjects compared to control subjects, but no significant difference at PD 17. qRT-PCR results suggest specific activation of the amygdala only in older subjects during auditory fear expression. A similar effect of age and conditioning status was also observed in the perirhinal cortex during both contextual and auditory fear expression. Overall, the development of fear conditioning occurring between the 3rd and 4th weeks of life appears to be at least partly attributable to changes in activation of the amygdala and perirhinal cortex during fear conditioning or expression. PMID:26820587

  1. Associations of macrolide and fluoroquinolone resistance with molecular typing in Streptococcus pyogenes from invasive infections, 2010-2012.

    PubMed

    Wajima, Takeaki; Morozumi, Miyuki; Chiba, Naoko; Shouji, Michi; Iwata, Satoshi; Sakata, Hiroshi; Ubukata, Kimiko

    2013-11-01

    In this study, the relationship between emm type and antibiotic resistance in 283 invasive group A streptococcal strains collected during surveillance from 2010 to 2012 was analysed. Strains were characterised by emm typing, multilocus sequence typing and antimicrobial susceptibility. Resistance rates for macrolide antibiotics conferred by mef(A), erm(A) or erm(B) were high (54.4%). The most prevalent (40.3%) macrolide resistance mediated by mef(A) was present in 92.2% of emm1 strains. It was found that 53.3% of emm12 strains and 91.7% of emm28 strains had erm(A) or erm(B) genes. Intermediate resistance to fluoroquinolones caused by a mutation in parC was found in 14.1% of strains. Furthermore, three strains (1.1%) with high resistance caused by mutations in both parC and gyrA were detected. Fluoroquinolone resistance was present in various emm types.

  2. A Kinesthetic Learning Approach to Earth Science for 3rd and 4th Grade Students on the Pajarito Plateau, Los Alamos, NM

    NASA Astrophysics Data System (ADS)

    Wershow, H. N.; Green, M.; Stocker, A.; Staires, D.

    2010-12-01

    Current efforts towards Earth Science literacy in New Mexico are guided by the New Mexico Science Benchmarks [1]. We are geoscience professionals in Los Alamos, NM who believe there is an important role for non-traditional educators utilizing innovative teaching methods. We propose to further Earth Science literacy for local 3rd and 4th grade students using a kinesthetic learning approach, with the goal of fostering an interactive relationship between the students and their geologic environment. We will be working in partnership with the Pajarito Environmental Education Center (PEEC), which teaches the natural heritage of the Pajarito Plateau to 3rd and 4th grade students from the surrounding area, as well as the Family YMCA’s Adventure Programs Director. The Pajarito Plateau provides a remarkable geologic classroom because minimal structural features complicate the stratigraphy and dramatic volcanic and erosional processes are plainly on display and easily accessible. Our methodology consists of two approaches. First, we will build an interpretive display of the local geology at PEEC that will highlight prominent rock formations and geologic processes seen on a daily basis. It will include a simplified stratigraphic section with field specimens and a map linked to each specimen’s location to encourage further exploration. Second, we will develop and implement a kinesthetic curriculum for an exploratory field class. Active engagement with geologic phenomena will take place in many forms, such as a scavenger hunt for precipitated crystals in the vesicles of basalt flows and a search for progressively smaller rhyodacite clasts scattered along an actively eroding canyon. We believe students will be more receptive to origin explanations when they possess a piece of the story. Students will be provided with field books to make drawings of geologic features. This will encourage independent assessment of phenomena and introduce the skill of scientific observation. We

  3. Surface interactions and degradation of a fluoroquinolone antibiotic in the dark in aqueous TiO2 suspensions

    DOE PAGES

    Peterson, Jonathan W.; Gu, Baohua; Seymour, Michael D.

    2015-06-15

    Fluoroquinolone antibiotics (FQs) are important drugs used in human and veterinary medicine. Their detection in natural waters and waste water treatment plants, along with increased resistance to FQs among some bacteria, have generated an increased interest in the fate of these drugs in the environment. Partitioning of FQs between an aqueous solution and attendant substrates depends, in part, on the surface reactivity of the adsorbent, commonly a function of particle size, surface charge, and functional groups. In this paper, this study investigated the surface interactions between the FQ drug ofloxacin (OFL) and titanium oxide (TiO2), a common catalyst and widely-observedmore » constituent in many consumer products. Raman and fluorescence spectroscopic techniques, as well as LC/MS, were used to determine the OFL moieties present on TiO2 surfaces and in attendant solutions. Raman spectra indicate that the C==O (ketone) group of the quinolone core, the NH+ of the piperazinyl ring, and CH3 of benzoxazine core are the most active in sorption onto the TiO2 surface. Raman spectra also show that the sorbed benzoxazine–quinolone core and piperazinyl moieties are readily desorbed from the surface by re-suspending samples in water. Importantly, we found that OFL could be degraded by reacting with TiO2 even in the dark. Complementary LC/MS analysis of the attendant supernatants indicates the presence of de-piperazinylated and de-carboxylated OFL breakdown products in supernatant solutions. Together, both Raman and LC/MS analyses indicate that TiO2 breaks the compound into piperazinyl and carboxylate groups which attach to the surface, whereas de-carboxylated and hydroxylated quinolone moieties remain in solution. Finally, the present study thus identifies the sorption mechanisms and breakdown products of OFL during dark reactions with TiO2, which is critically important for understanding the fate and transport of OFL as it enters the soil and aquatic environment.« less

  4. Surface interactions and degradation of a fluoroquinolone antibiotic in the dark in aqueous TiO2 suspensions

    SciTech Connect

    Peterson, Jonathan W.; Gu, Baohua; Seymour, Michael D.

    2015-06-15

    Fluoroquinolone antibiotics (FQs) are important drugs used in human and veterinary medicine. Their detection in natural waters and waste water treatment plants, along with increased resistance to FQs among some bacteria, have generated an increased interest in the fate of these drugs in the environment. Partitioning of FQs between an aqueous solution and attendant substrates depends, in part, on the surface reactivity of the adsorbent, commonly a function of particle size, surface charge, and functional groups. In this paper, this study investigated the surface interactions between the FQ drug ofloxacin (OFL) and titanium oxide (TiO2), a common catalyst and widely-observed constituent in many consumer products. Raman and fluorescence spectroscopic techniques, as well as LC/MS, were used to determine the OFL moieties present on TiO2 surfaces and in attendant solutions. Raman spectra indicate that the C==O (ketone) group of the quinolone core, the NH+ of the piperazinyl ring, and CH3 of benzoxazine core are the most active in sorption onto the TiO2 surface. Raman spectra also show that the sorbed benzoxazine–quinolone core and piperazinyl moieties are readily desorbed from the surface by re-suspending samples in water. Importantly, we found that OFL could be degraded by reacting with TiO2 even in the dark. Complementary LC/MS analysis of the attendant supernatants indicates the presence of de-piperazinylated and de-carboxylated OFL breakdown products in supernatant solutions. Together, both Raman and LC/MS analyses indicate that TiO2 breaks the compound into piperazinyl and carboxylate groups which attach to the surface, whereas de-carboxylated and hydroxylated quinolone moieties remain in solution. Finally, the present study thus identifies the sorption mechanisms and breakdown products of OFL during dark reactions with TiO2, which is critically important for understanding the

  5. Occurrence and sorption of fluoroquinolones in poultry litters and soils from São Paulo State, Brazil.

    PubMed

    Leal, Rafael Marques Pereira; Figueira, Rafael Fernandes; Tornisielo, Valdemar Luiz; Regitano, Jussara Borges

    2012-08-15

    Animal production is one of the most expressive sectors of Brazilian agro-economy. Although antibiotics are routinely used in this activity, their occurrence, fate, and potential impacts to the local environment are largely unknown. This research evaluated sorption-desorption and occurrence of four commonly used fluoroquinolones (norfloxacin, ciprofloxacin, danofloxacin, and enrofloxacin) in poultry litter and soil samples from São Paulo State, Brazil. The sorption-desorption studies involved batch equilibration technique and followed the OECD guideline for pesticides. All compounds were analyzed by HPLC, using fluorescence detector. Fluoroquinolones' sorption potential to the poultry litters (K(d) ≤65 L kg(-1)) was lower than to the soil (K(d) ~40,000 L kg(-1)), but was always high (≥69% of applied amount) indicating a higher specificity of fluoroquinolones interaction with soils. The addition of poultry litter (5%) to the soil had not affected sorption or desorption of these compounds. Desorption was negligible in the soil (≤0.5% of sorbed amount), but not in the poultry litters (up to 42% of sorbed amount). Fluoroquinolones' mean concentrations found in the poultry litters (1.37 to 6.68 mg kg(-1)) and soils (22.93 μg kg(-1)) were compatible to those found elsewhere (Austria, China, and Turkey). Enrofloxacin was the most often detected compound (30% of poultry litters and 27% of soils) at the highest mean concentrations (6.68 mg kg(-1) for poultry litters and 22.93 μg kg(-1) for soils). These results show that antibiotics are routinely used in poultry production and might represent one potential source of pollution to the environment that has been largely ignored and should be further investigated in Brazil.

  6. Activity of faropenem tested against Neisseria gonorrhoeae isolates including fluoroquinolone-resistant strains.

    PubMed

    Jones, Ronald N; Critchley, Ian A; Whittington, William L H; Janjic, Nebojsa; Pottumarthy, Sudha

    2005-12-01

    We evaluated the anti-gonococcal potency of faropenem along with 7 comparator reference antimicrobials against a preselected collection of clinical isolates. The 265 isolates were inclusive of 2 subsets: 1) 76 well-characterized resistant phenotypes of gonococcal strains (53 quinolone-resistant strains--31 with documented quinolone resistance-determining region changes from Japan, 15 strains resistant to penicillin and tetracycline, and 8 strains with intermediate susceptibility to penicillin) and 2) 189 recent isolates from clinical specimens in 2004 from 6 states across the United States where quinolone resistance is prevalent. Activity of faropenem was adversely affected by l-cysteine hydrochloride in IsoVitaleX (4-fold increase in [minimal inhibitory concentration] MIC50; 0.06 versus 0.25 microg/mL). The rank order of potency of the antimicrobials for the entire collection was ceftriaxone (MIC90, 0.06 microg/mL) > faropenem (0.25 microg/mL) > azithromycin (0.5 microg/mL) > cefuroxime (1 microg/mL) > tetracycline (2 microg/mL) > penicillin = ciprofloxacin = levofloxacin (4 microg/mL). Using MIC90 for comparison, faropenem was 4-fold more potent than cefuroxime (0.25 versus 1 microg/mL), but was 4-fold less active than ceftriaxone (0.25 versus 0.06 microg/mL). Although the activity of faropenem was not affected by either penicillinase production (MIC90, 0.12 microg/mL, penicillinase-positive) or increasing ciprofloxacin MIC (0.25 microg/mL, ciprofloxacin-resistant), increasing penicillin MIC was associated with an increase in MIC90 values (0.016 microg/mL for penicillin-susceptible to 0.25 microg/mL for penicillin-resistant strains). Among the recent (2004) clinical gonococcal isolates tested, reduced susceptibility to penicillins, tetracycline, and fluoroquinolones was high (28.0-94.2%). Geographic distribution of the endemic resistance rates of gonococci varied considerably, with 16.7-66.7% of the gonococcal isolates being ciprofloxacin-resistant in Oregon

  7. The reconstruction of the first copper-smelting processes in Europe during the 4th and the 3rd millennium BC: where does the oxygen come from?

    NASA Astrophysics Data System (ADS)

    Burger, E.; Bourgarit, D.; Wattiaux, A.; Fialin, M.

    2010-09-01

    From the end of Chalcolithic times (end of the 4th millennium BC) up to the end of the Bronze Age (1st millenium BC), copper production increases dramatically in Western Europe. However, due to the scarcity of technology-related archaeological data, the technological background sustaining the transition to mass production modes remains poorly understood. The main archaeological clues concerning metal production stem from the metallurgical waste, namely copper slags. Those complex materials may be a genuine chemical footprint of the process. In particular, it may bring new insights on one main issue of the process reconstruction: the origin of the oxygen in the system. A new analytical methodology based on both mass-balance calculation and quantification of Fe3+ contents in copper slags (Mössbauer spectroscopy, electronic microprobe and Synchrotron μ-XANES at the Fe-K-edge) has been set up. This methodology enables us to distinguish between the solid and gaseous sources of oxygen in a broad range of working conditions, thus yielding new features for the understanding of the first smelting processes dealing with copper sulphides in Western Europe 4000 years ago.

  8. Opportunities and Limitation of Hyporheic Restoration in a 4th Order Semi-Arid Floodplain: a Case Study of Meacham Creek, Oregon

    NASA Astrophysics Data System (ADS)

    O'Daniel, S. J.; Amerson, B. E.; Lambert, M. B.

    2014-12-01

    Persistent societal interest in improving water quality and recovering imperiled, native, aquatic species has expanded the scope of stream restoration to include the hyporheic zone as a focus. Despite the lack of detailed studies, hyporheic restoration is often invoked as a means to achieve multiple objectives including moderation of water temperature, delay of seasonal flows and increasing the localized volume of floodplain water. We present interim results from an ongoing case study that monitors the changes as a result of stream restoration of the hyporheic zone of a 4th order, alluvial floodplain in northeast Oregon, USA, Meacham Creek. Active and passive restoration of 2.5 km of Meacham Creek has altered the creek from a single-threaded, incised and bedrock-dominated channel to a perched, alluvial channel that seasonally exchanges overbank flows with the surrounding floodplain. Our results suggest that the stream restoration effort on Meacham Creek has increased the volume of annual hyporheic storage and created a more diverse distribution of flowpath lengths within the restoration site. Furthermore, our monitoring indicates that hyporheic process response to stream restoration, analogous to other geomorphic processes, conforms to a systematic hierarchy where nested flow paths range in length and residence time from meters and hours at the habitat scale to tens of meters and months at the floodplain scale. We assert that scale-explicit and measurement-focused restoration planning has a greater likelihood of meeting the stated objectives and result in improved water quality and encourage recovery of many native aquatic species.

  9. Dynamics of the properties of steppe paleosols of the Sarmatian time (2nd century BC-4th century AD) in relation to secular variations in climatic humidity

    NASA Astrophysics Data System (ADS)

    Demkin, V. A.; Zolotareva, B. N.; Demkina, T. S.; Khomutova, T. E.; Kashirskaya, N. N.; El'Tsov, M. V.; Udal'Tsov, S. N.

    2012-02-01

    Paleosols buried under kurgans of the Early (2nd-1st centuries BC), Middle (1st-2nd centuries AD) and Late (2nd-IV centuries AD) Sarmatian epochs were studied in dry steppes and desert steppes of the Lower Volga region (the Privolzhskaya and Ergeni Uplands and the Caspian Lowland). It was found that temporal variations in the morphological, chemical, microbiological, and magnetic properties of the paleosols in the interval of 2200-1600 BP were characterized by the cyclic pattern related to secular dynamics of climatic humidity with changes in the mean annual precipitation of ±30-50 mm. These climate changes did not transform chestnut paleosols and paleosolonetzes at the type or subtype taxonomic levels. However, they led to certain changes in the humus, carbonate, and salt profiles of the soils; in the character of solonetzic horizon B1; and in the state of microbial communities. According to these data, the Sarmatian time was characterized by alternation of micropluvial and microarid stages lasting fro about 100-200 years. In particular, the stages of humidization were observed in the 1st century BC-1st century AD and in the 4th century AD; the most arid conditions were observed in the second half of the 2nd and the first half of the 3rd century AD.

  10. Integrating data and mashup concepts in Hydro-Meteorological Research: the torrential rainfall event in Genoa (4th November 2011) case study.

    NASA Astrophysics Data System (ADS)

    Bedrina, T.; Parodi, A.; Quarati, A.; Clematis, A.; Rebora, N.; Laiosa, D.

    2012-04-01

    One of the critical issues in Hydro-Meteorological Research (HMR) is a better exploitation of data archives according to a multidisciplinary perspective. Different Earth science databases offer a huge amount of observational data, which often need to be assembled, processed, combined accordingly HM scientists needs. The cooperation between scientists active in HMR and Information and Communication Technologies (ICT) is essential in the development of innovative tools and applications for manipulating, aggregating and re-arranging heterogeneous information in flexible way. In this paper it is described an application devoted to the collection and integration of HM datasets, originated by public or private sources, freely exposed via Web services API. This application uses the mashup, recently become very popular in many fields, (Chow S.-W., 2007) technology concepts. Such methodology means combination of data and/or programs published by external online sources into an integrated experience. Mashup seems to be a promising methodology to respond to the multiple data-related activities into which HM researchers are daily involved (e.g. finding and retrieving high volume data; learning formats and developing readers; extracting parameters; performing filtering and mask; developing analysis and visualization tools). The specific case study of the recent extreme rainfall event, occurred over Genoa in Italy on the 4th November 2011 is shown through the integration of semi-professional weather observational networks as free available data source in addition to official weather networks.

  11. The structure of Diagnostic and Statistical Manual of Mental Disorders (4th edition, text revision) personality disorder symptoms in a large national sample.

    PubMed

    Trull, Timothy J; Vergés, Alvaro; Wood, Phillip K; Jahng, Seungmin; Sher, Kenneth J

    2012-10-01

    We examined the latent structure underlying the criteria for DSM-IV-TR (American Psychiatric Association, 2000, Diagnostic and statistical manual of mental disorders (4th ed., text revision). Washington, DC: Author.) personality disorders in a large nationally representative sample of U.S. adults. Personality disorder symptom data were collected using a structured diagnostic interview from approximately 35,000 adults assessed over two waves of data collection in the National Epidemiologic Survey on Alcohol and Related Conditions. Our analyses suggested that a seven-factor solution provided the best fit for the data, and these factors were marked primarily by one or at most two personality disorder criteria sets. A series of regression analyses that used external validators tapping Axis I psychopathology, treatment for mental health problems, functioning scores, interpersonal conflict, and suicidal ideation and behavior provided support for the seven-factor solution. We discuss these findings in the context of previous studies that have examined the structure underlying the personality disorder criteria as well as the current proposals for DSM-5 personality disorders.

  12. Evidence of human-induced morphodynamic changes along the Campania coastal areas (southern Italy) since the 3rd-4th cent. AD

    NASA Astrophysics Data System (ADS)

    Russo Ermolli, Elda; Romano, Paola; Liuzza, Viviana; Amato, Vincenzo; Ruello, Maria Rosaria; Di Donato, Valentino

    2014-05-01

    Campania has always offered suitable climatic and physiographic conditions for human settlements since prehistoric times. In particular, many Graeco-Roman towns developed along its coasts starting from the 7th-6th cent. BC. In the last decade, geoarchaelogical surveys have been carried out in the archaeological excavations of Neapolis, Paestum and Elea-Velia allowing the main steps of the landscape evolution around these towns to be defined in detail. The greek town of Neapolis rose in the late 6th cent. BC [1] on a terrace overlooking a low-relief rocky coast surrounded by volcanic hills. Port activities developed in a protected bay facing the town from the 4th-2nd cent. BC up to the 4th cent. AD, as testified by the discovery of structures and shipwrecks [2, 3, 4]. Starting from the 3rd cent. AD a spit bar formed at the bay entrance causing the progressive establishment of a lagoon which was gradually filled up by alluvial inputs and completely closed in the 5th cent. AD. During the same period, episodes of increased alluvial inputs were also recorded further west along the coast, where a narrow sandy beach formed at the cliff toe. The greek town of Poseidonia, renamed Paestum by the Romans, was founded in the 540 BC on a travertine terrace facing the sandy littoral of a prograding coastal plain [5]. In front of the main town door, a coastal lagoon developed thanks to the growth of a dune ridge and was probably used for harbor activities [5]. After this period the shoreline shifted seawards, another dune ridge formed and the back-ridge depression was filled with fluvial-marshy deposits, slowly drying up. Phases of travertine deposition, which characterized the SE sector of the plain all along the Holocene, were recorded in the northern and southern quarters of the town in historical times and were connected to the abandonment of the town in the early Medieval times. The greek colony of Elea-Velia was located on top of a siliciclastic promontory where the ruins of

  13. Status and Trend of Regal Fritillary (Speyeria idalia) (Lepidoptera: Nymphalidae) in the 4th of July Butterfly Count Program in 1977-2014.

    PubMed

    Swengel, Scott R; Swengel, Ann B

    2016-01-01

    Regal Fritillary (Speyeria idalia) primarily inhabits prairie, a native grassland of central North America, and occurs rarely in nonprairie grasslands further east. This butterfly has experienced widespread decline and marked range contraction. We analyze Regal Fritillary incidence and abundance during 1977-2014 in 4th of July Butterfly Counts, an annual census of butterflies in North America. Volunteers count within the same 24 km diameter circle each year. Only 6% of counts in range reported a Regal, while 18% of counts in core range in the Midwest and Great Plains did. 99.9% of Regal individuals occurred in core range. Only four circles east of core range reported this species, and only during the first half of the study period. All individuals reported west of its main range occurred in two circles in Colorado in the second half of the study. The number of counts per year and survey effort per count increased during the study. During 1991-2014, >31 counts occurred per year in core Regal range, compared to 0-23 during 1975-1990. During 1991-2014, all measures of Regal presence and abundance declined, most significantly. These results agree with other sources that Regal Fritillary has contracted its range and declined in abundance. PMID:27239370

  14. Future perspectives in melanoma research. Meeting report from the “Melanoma Bridge. Napoli, December 2nd-4th 2012”

    PubMed Central

    2013-01-01

    Recent insights into the genetic and somatic aberrations have initiated a new era of rapidly evolving targeted and immune-based treatments for melanoma. After decades of unsuccessful attempts to finding a more effective cure in the treatment of melanoma now we have several drugs active in melanoma. The possibility to use these drugs in combination to improve responses to overcome the resistance, to potentiate the action of immune system with the new immunomodulating antibodies, and identification of biomarkers that can predict the response to a particular therapy represent new concepts and approaches in the clinical management of melanoma. The third “Melanoma Research: “A bridge from Naples to the World” meeting, shortened as “Bridge Melanoma Meeting” took place in Naples, December 2 to 4th, 2012. The four topics of discussion at this meeting were: advances in molecular profiling and novel biomarkers, combination therapies, novel concepts toward integrating biomarkers and therapies into contemporary clinical management of patients with melanoma across the entire spectrum of disease stage, and the knowledge gained from the biology of tumor microenvironment across different tumors as a bridge to impact on prognosis and response to therapy in melanoma. This international congress gathered more than 30 international faculty members who in an interactive atmosphere which stimulated discussion and exchange of their experience regarding the most recent advances in research and clinical management of melanoma patients. PMID:23731854

  15. Status and Trend of Regal Fritillary (Speyeria idalia) (Lepidoptera: Nymphalidae) in the 4th of July Butterfly Count Program in 1977-2014.

    PubMed

    Swengel, Scott R; Swengel, Ann B

    2016-01-01

    Regal Fritillary (Speyeria idalia) primarily inhabits prairie, a native grassland of central North America, and occurs rarely in nonprairie grasslands further east. This butterfly has experienced widespread decline and marked range contraction. We analyze Regal Fritillary incidence and abundance during 1977-2014 in 4th of July Butterfly Counts, an annual census of butterflies in North America. Volunteers count within the same 24 km diameter circle each year. Only 6% of counts in range reported a Regal, while 18% of counts in core range in the Midwest and Great Plains did. 99.9% of Regal individuals occurred in core range. Only four circles east of core range reported this species, and only during the first half of the study period. All individuals reported west of its main range occurred in two circles in Colorado in the second half of the study. The number of counts per year and survey effort per count increased during the study. During 1991-2014, >31 counts occurred per year in core Regal range, compared to 0-23 during 1975-1990. During 1991-2014, all measures of Regal presence and abundance declined, most significantly. These results agree with other sources that Regal Fritillary has contracted its range and declined in abundance.

  16. Status and Trend of Regal Fritillary (Speyeria idalia) (Lepidoptera: Nymphalidae) in the 4th of July Butterfly Count Program in 1977–2014

    PubMed Central

    2016-01-01

    Regal Fritillary (Speyeria idalia) primarily inhabits prairie, a native grassland of central North America, and occurs rarely in nonprairie grasslands further east. This butterfly has experienced widespread decline and marked range contraction. We analyze Regal Fritillary incidence and abundance during 1977–2014 in 4th of July Butterfly Counts, an annual census of butterflies in North America. Volunteers count within the same 24 km diameter circle each year. Only 6% of counts in range reported a Regal, while 18% of counts in core range in the Midwest and Great Plains did. 99.9% of Regal individuals occurred in core range. Only four circles east of core range reported this species, and only during the first half of the study period. All individuals reported west of its main range occurred in two circles in Colorado in the second half of the study. The number of counts per year and survey effort per count increased during the study. During 1991–2014, >31 counts occurred per year in core Regal range, compared to 0–23 during 1975–1990. During 1991–2014, all measures of Regal presence and abundance declined, most significantly. These results agree with other sources that Regal Fritillary has contracted its range and declined in abundance. PMID:27239370

  17. Highly sensitive detection of five typical fluoroquinolones in low-fat milk by field-enhanced sample injection-based CE in bubble cell capillary.

    PubMed

    Deng, Yan; Gasilova, Natalia; Qiao, Liang; Zhou, Ying-Lin; Zhang, Xin-Xiang; Girault, Hubert H

    2014-12-01

    Fluoroquinolones are a group of synthetic antibiotics with a broad activity spectrum against mycoplasma, Gram-positive, and Gram-negative bacteria. Due to the extensive use of fluoroquinolones in farming and veterinary science, there is a constant need in the analytical methods able to efficiently monitor their residues in food products of animal origin, regulated by Commission Regulation (European Union) no. 37/2010. Herein, field-enhanced sample injection for sample stacking prior the CZE separation was developed inside a bubble cell capillary for highly sensitive detection of five typical fluoroquinolones in bovine milk. Ethylenediamine was proposed as the main component of BGE for the antibiotics separation. The effect of BGE composition, injection parameters, and water plug length on the field-enhanced sample injection-based CE with UV detection was investigated. Under the optimized conditions, described field-enhanced sample injection-based CE-UV analysis of fluoroquinolones provides LODs varying from 0.4 to 1.3 ng/mL. These LOD values are much lower (from 460 to 1500 times) than those obtained by a conventional CE in a standard capillary without bubble cell. The developed method was finally applied for the analysis of fluoroquinolones in low-fat milk from a Swiss supermarket. Sample recovery values from 93.6 to 106.0% for different fluoroquinolones, and LODs from 0.7 to 2.5 μg/kg, were achieved. Moreover, the proposed ethylenediamine-based BGE as volatile and compatible with MS system, enabled the coupling of the field-enhanced sample injection-based CE with a recently introduced electrostatic spray ionization MS via an iontophoretic fraction collection interface for qualitative fluoroquinolones identification.

  18. Isolation of a non-genomic origin fluoroquinolone responsive regulatory element using a combinatorial bioengineering approach

    PubMed Central

    Srivastava, Santosh Kumar; Iyer, V. Rajesh; Ghosh, Tamoghna; Lambadi, Paramesh Ramulu; Pathania, Ranjana; Navani, Naveen Kumar

    2016-01-01

    Advances in chemical biology have led to selection of synthetic functional nucleic acids for in vivo applications. Discovery of synthetic nucleic acid regulatory elements has been a long-standing goal of chemical biologists. Availability of vast genome level genetic resources has motivated efforts for discovery and understanding of inducible synthetic genetic regulatory elements. Such elements can lead to custom-design of switches and sensors, oscillators, digital logic evaluators and cell–cell communicators. Here, we describe a simple, robust and universally applicable module for discovery of inducible gene regulatory elements. The distinguishing feature is the use of a toxic peptide as a reporter to suppress the background of unwanted bacterial recombinants. Using this strategy, we show that it is possible to isolate genetic elements of non-genomic origin which specifically get activated in the presence of DNA gyrase A inhibitors belonging to fluoroquinolone (FQ) group of chemicals. Further, using a system level genetic resource, we prove that the genetic regulation is exerted through histone-like nucleoid structuring (H-NS) repressor protein. Till date, there are no reports of in vivo selection of non-genomic origin inducible regulatory promoter like elements. Our strategy opens an uncharted route to discover inducible synthetic regulatory elements from biologically-inspired nucleic acid sequences. PMID:26837578

  19. The occurrence and removal of selected fluoroquinolones in urban drinking water treatment plants.

    PubMed

    Xu, Yongpeng; Chen, Ting; Wang, Yuan; Tao, Hui; Liu, Shiyao; Shi, Wenxin

    2015-12-01

    Fluoroquinolones (FQs) are a widely prescribed group of antibiotics. They enter the aqueous environment, where they are frequently detected, and can lead to a threat to human health. Drinking water treatment plants (DWTPs) play a key role in removing FQs from potable water. This study investigated the occurrence and removal of four selected FQs (norfloxacin (NOR), ciprofloxacin (CIP), enrofloxacin (ENR), and ofloxacin (OFL)) in three urban DWTPs in China. The treatment efficacy for each system was simultaneously evaluated. Two of the examined DWTPs used conventional treatment processes. The third used conventional processes followed by additional treatment processes (ozonation-biologically activated carbon (ozonation-BAC) and membrane technology). The average concentrations of the four FQs in the source water and the finished water ranged from 51 to 248 ng/L and from <5 to 46 ng/L, respectively. Based on residual concentrations, the conventional treatment system had a low removal of FQs. In contrast, the addition of advanced treatment processes such as the ozonation-BAC and membranes, substantially improved the removal of FQs. The finding of this study has important implications: even though coagulation-sedimentation and chlorination treatment processes can remove most target FQs, the typical practice of advanced treatment processes is necessary for the further removal.

  20. Adsorptive Removal and Adsorption Kinetics of Fluoroquinolone by Nano-Hydroxyapatite.

    PubMed

    Chen, Yajun; Lan, Tao; Duan, Lunchao; Wang, Fenghe; Zhao, Bin; Zhang, Shengtian; Wei, Wei

    2015-01-01

    Various kinds of antibiotics, especially fluoroquinolone antibiotics (FQs) have been widely used for the therapy of infectious diseases in human and livestock. For their poorly absorbed by living organisms, large-scale misuse or abuse of FQs will foster drug resistance among pathogenic bacteria, as well as a variety of environmental problems when they were released in the environment. In this work, the adsorption properties of two FQs, namely norfloxacin (NOR) and ciprofloxacin (CIP), by nano-hydroxyapatite (n-HAP) were studied by batch adsorption experiments. The adsorption curves of FQs by n-HAP were simulated by Langmuir and Freundlich isotherms. The results shown that NOR and CIP can be adsorbed effectively by the adsorbent of n-HAP, and the adsorption capacity of FQs increase with increasing dosage of n-HAP. The optimum dosage of n-HAP for FQs removal was 20 g · L(-1), in which the removal efficiencies is 51.6% and 47.3%, and an adsorption equilibrium time is 20 min. The maximum removal efficiency occurred when pH is 6 for both FQs. The adsorption isotherm of FQs fits well for both Langmuir and Freundlich equations. The adsorption of both FQs by n-HAP follows second-order kinetics. PMID:26698573

  1. Improved extraction of fluoroquinolones with recyclable ionic-liquid-based aqueous biphasic systems†

    PubMed Central

    Almeida, Hugo F. D.; Freire, Mara G.; Marrucho, Isabel M.

    2016-01-01

    In the past few years, the improvement of advanced analytical tools allowed to confirm the presence of trace amounts of metabolized and unchanged active pharmaceutical ingredients (APIs) in wastewater treatment plants (WWTPs) as well as in freshwater surfaces. It is known that the continuous contact with APIs, even at very low concentrations (ng L−1–μg L−1), leads to serious human health problems. In this context, this work shows the feasibility of using ionic-liquid-based aqueous biphasic systems (IL-based ABS) in the extraction of quinolones present in aqueous media. In particular, ABS composed of imidazolium- and phosphonium-based ILs and aluminium-based salts (already used in water treatment plants) were evaluated in one-step extractions of six fluoroquinolones (FQs), namely ciprofloxacin, enrofloxacin, moxifloxacin, norfloxacin, ofloxacin and sarafloxacin, and extraction efficiencies up to 98% were obtained. Despite the large interest devoted to IL-based ABS as extractive systems of outstanding performance, their recyclability/reusability has seldomly been studied. An efficient extraction/cleaning process of the IL-rich phase is here proposed by FQs induced precipitation. The recycling of the IL and its further reuse without losses in the ABS extractive performance for FQs were established, as confirmed by the four consecutive removal/extraction cycles evaluated. This novel recycling strategy supports IL-based ABS as sustainable and cost-efficient extraction platforms.

  2. Adsorptive Removal and Adsorption Kinetics of Fluoroquinolone by Nano-Hydroxyapatite

    PubMed Central

    Chen, Yajun; Lan, Tao; Duan, Lunchao; Wang, Fenghe; Zhao, Bin; Zhang, Shengtian; Wei, Wei

    2015-01-01

    Various kinds of antibiotics, especially fluoroquinolone antibiotics (FQs) have been widely used for the therapy of infectious diseases in human and livestock. For their poorly absorbed by living organisms, large-scale misuse or abuse of FQs will foster drug resistance among pathogenic bacteria, as well as a variety of environmental problems when they were released in the environment. In this work, the adsorption properties of two FQs, namely norfloxacin (NOR) and ciprofloxacin (CIP), by nano-hydroxyapatite (n-HAP) were studied by batch adsorption experiments. The adsorption curves of FQs by n-HAP were simulated by Langmuir and Freundlich isotherms. The results shown that NOR and CIP can be adsorbed effectively by the adsorbent of n-HAP, and the adsorption capacity of FQs increase with increasing dosage of n-HAP. The optimum dosage of n-HAP for FQs removal was 20 g·L-1, in which the removal efficiencies is 51.6% and 47.3%, and an adsorption equilibrium time is 20 min. The maximum removal efficiency occurred when pH is 6 for both FQs. The adsorption isotherm of FQs fits well for both Langmuir and Freundlich equations. The adsorption of both FQs by n-HAP follows second-order kinetics. PMID:26698573

  3. Fluoroquinolones: A micro-species equilibrium in the protonation of amphoteric compounds.

    PubMed

    Nurchi, Valeria M; Crisponi, Guido; Lachowicz, Joanna I; Zoroddu, Maria Antonietta; Peana, Massimiliano; Medici, Serenella; Veclani, Daniele; Tolazzi, Marilena; Melchior, Andrea

    2016-10-10

    The knowledge of the speciation of fluoroquinolones is of great actuality for the implications on the activity, bioavailability and pharmacokinetics. Literature reports a number of contrasting evaluations on the existence of tautomeric forms of mono-protonated species, described by a set of protonation micro-constants. Here the protonation sequence and the related protonation constants of four representative molecules are evaluated by a combined potentiometric-spectrophotometric method. The experimental observations necessary to differentiate between a protonation scheme represented by macro-constants alone, and the one that requires the introduction of a micro-protonation scheme, are clearly delineated based on a careful analysis of experimental data and of simulated models. The role of the medium was investigated and UV-vis spectra in water- methanol solution were analyzed. The existence of the zwitterionic species alone at physiological pH in water, and an increase of the relative amount of the neutral species with the lipophilicity of the medium were remarked. This surely affects the bioavailability of FQs, with the increase of the neutral species when the molecules approach the local lipophilic environment close to the cellular membranes. NMR studies allowed the attribution of the protonation sites of the different forms. Quantum chemical evaluation of all the possible existent forms with different protonation degrees and in different sites strongly substantiates the experimental results. The study of the relevant frontier molecular orbitals completed the detailed theoretical characterization of the species. PMID:27586021

  4. Biotransformation of fluoroquinolone antibiotics by ligninolytic fungi--Metabolites, enzymes and residual antibacterial activity.

    PubMed

    Čvančarová, Monika; Moeder, Monika; Filipová, Alena; Cajthaml, Tomáš

    2015-10-01

    A group of white rot fungi (Irpex lacteus, Panus tigrinus, Dichomitus squalens, Trametes versicolor and Pleurotus ostreatus) was investigated for the biodegradation of norfloxacin (NOR), ofloxacin (OF) and ciprofloxacin (CIP). The selected fluoroquinolones were readily degraded almost completely by I. lacteus and T. versicolor within 10 and 14 d of incubation in liquid medium, respectively. The biodegradation products were identified by liquid chromatography-mass spectrometry. The analyses indicated that the fungi use similar mechanisms to degrade structurally related antibiotics. The piperazine ring of the molecules is preferably attacked via either substitution or/and decomposition. In addition to the degradation efficiency, attention was devoted to the residual antibiotic activities estimated using Gram-positive and Gram-negative bacteria. Only I. lacteus was able to remove the antibiotic activity during the course of the degradation of NOR and OF. The product-effect correlations evaluated by Principal Component Analysis (PCA) enabled elucidation of the participation of the individual metabolites in the residual antibacterial activity. Most of the metabolites correlated with the antibacterial activity, explaining the rather high residual activity remaining after the biodegradation. PCA of ligninolytic enzyme activities indicated that manganese peroxidase might participate in the degradation.

  5. Improved extraction of fluoroquinolones with recyclable ionic-liquid-based aqueous biphasic systems†

    PubMed Central

    Almeida, Hugo F. D.; Freire, Mara G.; Marrucho, Isabel M.

    2016-01-01

    In the past few years, the improvement of advanced analytical tools allowed to confirm the presence of trace amounts of metabolized and unchanged active pharmaceutical ingredients (APIs) in wastewater treatment plants (WWTPs) as well as in freshwater surfaces. It is known that the continuous contact with APIs, even at very low concentrations (ng L−1–μg L−1), leads to serious human health problems. In this context, this work shows the feasibility of using ionic-liquid-based aqueous biphasic systems (IL-based ABS) in the extraction of quinolones present in aqueous media. In particular, ABS composed of imidazolium- and phosphonium-based ILs and aluminium-based salts (already used in water treatment plants) were evaluated in one-step extractions of six fluoroquinolones (FQs), namely ciprofloxacin, enrofloxacin, moxifloxacin, norfloxacin, ofloxacin and sarafloxacin, and extraction efficiencies up to 98% were obtained. Despite the large interest devoted to IL-based ABS as extractive systems of outstanding performance, their recyclability/reusability has seldomly been studied. An efficient extraction/cleaning process of the IL-rich phase is here proposed by FQs induced precipitation. The recycling of the IL and its further reuse without losses in the ABS extractive performance for FQs were established, as confirmed by the four consecutive removal/extraction cycles evaluated. This novel recycling strategy supports IL-based ABS as sustainable and cost-efficient extraction platforms. PMID:27642262

  6. Membrane localization and topology of the DnpA protein control fluoroquinolone tolerance in Pseudomonas aeruginosa.

    PubMed

    Liebens, Veerle; Frangipani, Emanuela; Van der Leyden, Annelies; Fauvart, Maarten; Visca, Paolo; Michiels, Jan

    2016-09-01

    DnpA, a putative de-N-acetylase of the PIG-L superfamily, is required for antibiotic tolerance in Pseudomonas aeruginosa Exactly how dnpA (gene locus PA5002) directs the formation of antibiotic-tolerant persister cells is currently unknown. Previous research provided evidence for a role in surface-associated process(es), possibly in lipopolysaccharide biosynthesis. In silico sequence analysis of DnpA predicts a single transmembrane domain and Nin/Cout orientation of DnpA. In contrast, we here show that DnpA is an integral inner membrane protein containing two transmembrane domains, with the major C-terminal part located at the cytoplasmic face. Correct insertion into the inner membrane is necessary for DnpA to promote fluoroquinolone tolerance. The membrane localization of DnpA further supports its role in cell envelope-associated process(es). In addition to shedding light on the biological role of DnpA, this study highlights the risks of overreliance on the predictive value of bioinformatics tools and the importance of rigorous experimental validation of in silico predictions. PMID:27481702

  7. Exploring the contribution of efflux on the resistance to fluoroquinolones in clinical isolates of Escherichia coli.

    PubMed

    Paltansing, Sunita; Tengeler, Anouk C; Kraakman, Margriet E M; Claas, Eric C J; Bernards, Alexandra T

    2013-12-01

    Resistance to ciprofloxacin in Escherichia coli is increasing parallel to increased use of fluoroquinolones both in The Netherlands and in other European countries. The objective was to investigate the contribution of active efflux and expression of outer membrane proteins (OMPs) in a collection of clinical E. coli isolates collected at a clinical microbiology department in a Dutch hospital. Forty-seven E. coli isolates a wide range of ciprofloxacin minimum inhibitory concentrations and known mutations in the quinolone resistance determining region were included. A fluorometric determination of bisbenzimide efflux was used two different efflux pump inhibitors and compared to quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for the expression levels of acrA, acrB, tolC, yhiV, and mdfA efflux pump genes and the OMPs ompF and ompX. Six isolates (12.7%) showed increased efflux. Although in 35 isolates (76%), overexpression of ≥1 efflux pump genes using qRT-PCR was present. Only the combined overexpression of acrAB-TolC and mdfA correlated with the phenotypic efflux assay using glucose/carbonyl cyanide m-chlorophenylhydrazone with glucose. Thus, efflux was involved in ciprofloxacin resistance in a limited number of E. coli isolates collected at a clinical microbiology department in a Dutch hospital complementing other resistance mechanisms.

  8. Rapid determination of fluoroquinolone residues in honey by a microbiological screening method and liquid chromatography.

    PubMed

    Kanda, Maki; Kusano, Tomoto; Kanai, Setsuko; Hayashi, Hiroshi; Matushima, Yoko; Nakajima, Takayuki; Takeba, Kazue; Sasamoto, Takeo; Nagayma, Toshijiro

    2010-01-01

    A rapid and efficient method was developed for the simultaneous determination of seven fluoroquinolone (FQ) residues: norfloxacin, ciprofloxacin, danofloxacin, enrofloxacin, orbifloxacin, sarafloxacin, and difloxacin in honey. The samples were first screened with a microbiological method by using test plates made from metal-free purified agar seeded with Bacillus subtilis BGA. When a sample was found to contain FQ residues by using the microbiological method, it was analyzed by LC with fluorescence detection (LC/FL). FQs were extracted with Na2EDTA-McIlvaine buffer and purified by a dual SPE method in which a cation-exchange cartridge was connected to an anion-exchange cartridge. The overall recoveries of the seven FQs ranged from 70.0 to 92.1%. The intra-assay and interassay CVs were < or = 7.8 and < or = 5.1%, respectively. For the microbiological method, the LOD values ranged from 2 to 9 microg/kg. For LC/FL, the LOQ values ranged from 2 to 7 microg/kg. The developed method was used to analyze 70 honey samples. In 14 samples in which the microbiological method detected the presence of FQ residues, norfloxacin, ciprofloxacin, and enrofloxacin were identified by LC/FL.

  9. [Contamination characteristics of fluoroquinolones in different kinds of soil profiles in Southeast suburb of Beijing].

    PubMed

    Su, Si-Hui; He, Jiang-Tao; Yang, Lei; Qiao, Xiao-Cui; Cui, Ya-Feng

    2014-11-01

    Eighty-six soil samples were collected using Geoprobe soil sampler from 11 borehole profiles of Beijing Southeast suburb. The sampling sites could be divided into 8 kinds of landuse. Physical and chemical properties of samples were analyzed. The concentrations of 5 fluoroquinolones (FQs) were analyzed by the high-performance liquid chromatography. Results show that the average value of total concentrations of 5 FQs is 46.1 μg x kg(-1). Ofloxacin (OFL) is the predominant among them, and then is norfloxacin (NOR). Last comes to enrofloxacin (ENR), ciprofloxacin (CIP) and lomefloxacin (LOM). There are significant differences in FQs concentrations and kinds among the 8 land use types of soil profiles. The average value of total concentrations of 5 FQs decrease with an increasing of soil depth. The average concentration of OFL, NOR, LOM and ENR decrease with an increasing of soil depth. But CIP has the opposite result. Based on FQs concentrations from 42 soil samples with a depth among 0 to 3 meters, contamination characteristics of FQs were analyzed by fuzzy hierarchial clustering. Sampling sites of vegetable greenhouse, woods, sewage irrigation zone, groundwater irrigation zone, livestock and poultry farm, sediments from sewage river have similar components and contents of FQs, with less kinds and low concentration. In contrast, sampling sites of pharmaceutical enterprises and refuse landfill have more kinds and medium concentration of FQs.

  10. Risk assessment of three fluoroquinolone antibiotics in the groundwater recharge system.

    PubMed

    Chen, Guoli; Liu, Xiang; Tartakevosky, Daniel; Li, Miao

    2016-11-01

    Three fluoroquinolone antibiotics agents (FQs) in groundwater and reclaimed water have been investigated in Changzhou and Beijing, China. The occurrence of ofloxacin (OFL), enrofloxacin (ENR) and norfloxacin (NOR) is in nanograms per liter and has 100% frequency. The concentration order of FQs in reclaimed water is NOR>OFL>ENR, whilst the order in groundwater is NOR>ENR>OFL. And then the single and mixture adsorption-desorption have been studied and showed that (i) silty clay loam has higher sorption capacity than loamy sand, (ii) competitive adsorption exists when the three selected FQs coexist, (iii) ENR has a significantly priority sorption to NOR, whilst OFL has a least sorption among the mixture, (iv) there is no significant difference between the desorption results of mixture and the indivdual compound in relatively low concentration, (v) the formed chemical bonds and the irreversible combination of adsorption point are the significant influential factors for explaining desorption hysteresis of the selected FQs. Based on the above study, transport model and risk quotient have been performed, and the calculated risk quotient reveals that: (i) the selected FQs risk order in reclaimed water is OFL>ENR>NOR, (ii) in groundwater, OFL and ENR pose a higher risk than NOR no matter whether considering the long time groundwater recharge. This study will help policy makers to decide which FQs need to be covered in the priority substance lists defined in legislative frameworks. PMID:27400060

  11. [Distribution Characteristics of Fluoroquinolones Antibiotics in Surface Water and Groundwater from Typical Areas in A City].

    PubMed

    Cui, Ya-feng; He, Jiang-tao; Su, Si-hui; Yang, Lei; Qiao, Xiao-cui

    2015-11-01

    In order to investigate the characteristics of 5 typical kinds of fluoroquinolones (FQs) pollution in waters from a city, surface water and groundwater samples from main drainage rivers and typical areas were collected, respectively. The conventional test and FQs concentrations analysis of the water samples were conducted. The results showed the concentration and composition of FQs in groundwater differed substantially from those in surface water. The average concentration of FQs in surface water was 789.1 ng x L(-1) with the main components of ofloxacin (OFL) and lomefloxacin (LOM). This value was higher than the average concentration of FQs in groundwater: 342.7 ng x L(-1) with the main components of norfloxacin (NOR) and lomefloxacin (LOM). The enrofloxacin (ENR) exhibited relatively lower levels in both surface water and groundwater as compared to others. The highest FQs concentrations in surface water were found in trenches, followed by tributaries and the main stream. For groundwater, FQs concentrations were relatively higher in the sewage riverside. A decreasing trend of FQs concentration was monitored with the increasing distance of sampling points to the drainage rivers and all components mentioned above showed similar changing trends. The results of this study preliminarily indicated that FQs in groundwater along the riverside probably came from the surface water.

  12. Effects of Fluoroquinolones and Azithromycin on Biofilm Formation of Stenotrophomonas maltophilia.

    PubMed

    Wang, Aihua; Wang, Qinqin; Kudinha, Timothy; Xiao, Shunian; Zhuo, Chao

    2016-01-01

    Stenotrophomonas maltophilia is an opportunistic pathogen that causes respiratory and urinary tract infections, as well as wound infections in immunocompromised patients. This pathogen is difficult to treat due to increased resistance to many antimicrobial agents. We investigated the in vitro biofilm formation of S. maltophilia, including effects of fluoroquinolones (FQs) and azithromycin on biofilm formation. The organism initiated attachment to polystyrene surfaces after a 4 h incubation period, and reached maximal growth at 18-24 h. In the presence of FQs (moxifloxacin, levofloxacin or ciprofloxacin), the biofilm biomass was significantly reduced (P < 0.05). A lower concentration of moxifloxacin (10 μg/mL) exhibited a better inhibiting effect on biofilm formation than 100 μg/mL (P < 0.01), but with no difference in effect compared to the 50 μg/mL concentration (P > 0.05). However, the inhibitory effects of 10 μg/mL of levofloxacin or ciprofloxacin were slightly less pronounced than those of the higher concentrations. A combination of azithromycin and FQs significantly reduced the biofilm inhibiting effect on S. maltophilia preformed biofilms compared to azithromycin or FQs alone. We conclude that early use of clinically acceptable concentrations of FQs, especially moxifloxacin (10 μg/mL), may possibly inhibit biofilm formation by S. maltophilia. Our study provides an experimental basis for a possible optimal treatment strategy for S. maltophilia biofilm-related infections.

  13. Tolerance of Escherichia coli to fluoroquinolone antibiotics depends on specific components of the SOS response pathway.

    PubMed

    Theodore, Alyssa; Lewis, Kim; Vulic, Marin

    2013-12-01

    Bacteria exposed to bactericidal fluoroquinolone (FQ) antibiotics can survive without becoming genetically resistant. Survival of these phenotypically resistant cells, commonly called "persisters," depends on the SOS gene network. We have examined mutants in all known SOS-regulated genes to identify functions essential for tolerance in Escherichia coli. The absence of DinG and UvrD helicases and the Holliday junction processing enzymes RuvA and RuvB leads to a decrease in survival. Analysis of the respective mutants indicates that, in addition to repair of double-strand breaks, tolerance depends on the repair of collapsed replication forks and stalled transcription complexes. Mutation in recF results in increased survival, which identifies RecAF recombination as a poisoning mechanism not previously linked to FQ lethality. DinG acts upstream of SOS promoting its induction, whereas RuvAB participates in repair only. UvrD directly promotes all repair processes initiated by FQ-induced damage and prevents RecAF-dependent misrepair, making it one of the crucial SOS functions required for tolerance.

  14. Bridging the US and China together to conquer cancer: report of the 4th annual meeting of the US Chinese Anti-Cancer Association (USCACA).

    PubMed

    Yang, Wancai; Guan, Lingjie

    2012-07-01

    A global collaborative effort is pivotal to conquer cancer. Themed "Emerging role of China in global clinical development of novel anti-cancer drugs", the US Chinese Anti-Cancer Association (USCACA) held its 4th annual meeting in Chicago on June 2, 2012, in conjunction with the American Society of Clinical Oncology (ASCO) annual meeting to further bridge the US and China together to outsmart cancer. Although a young organization, USCACA has made significant contributions to this goal in the 3 years since its inception through extensive collaboration with academic organizations, the pharmaceutical industry, and governmental agencies. USCACA has engaged various stakeholders in developing translational and personalized medical strategies to facilitate new anti-cancer drug development and clinical trials in China. USCACA has initiated and implemented the USCACA-National Foundation for Cancer Research (NFCR) scholarship to encourage overseas returnees to continue cancer research in China. USCACA announced the Hengrui-USCACA scholarship to fund clinical trial staff from China to conduct the observation of early oncologic clinical trials in the US. During the annual meeting, distinguished panelists and the audience discussed the following critical topics:(1) oncologic translational research and early development capabilities in China;(2) novel chemical entity development and partnership with Chinese companies; and (3) Chinese participation in global anti-cancer drug development. USCACA will continue to promote collaborations among cancer researchers and clinicians in the US and China by engaging in more frequent communications and joint efforts across fields, disciplines, and countries, diligently working together toward curing and eliminating cancers. PMID:22739264

  15. Changes in the regional prevalence of child obesity in 4th, 8th, and 11th grade students in Texas from 2000-2002 to 2004-2005.

    PubMed

    Hoelscher, Deanna M; Kelder, Steven H; Pérez, Adriana; Day, R Sue; Benoit, Julia S; Frankowski, Ralph F; Walker, Joey L; Lee, Eun S

    2010-07-01

    Although national and state estimates of child obesity are available, data at these levels are insufficient to monitor effects of local obesity prevention initiatives. The purpose of this study was to examine regional changes in the prevalence of obesity due to statewide policies and programs among children in grades 4, 8, and 11 in Texas Health Services Regions (HSRs) between 2000-2002 and 2004-2005, and nine selected counties in 2004-2005. A cross-sectional, probability-based sample of 23,190 Texas students in grades 4, 8, and 11 were weighed and measured to obtain BMI. Obesity was >95th percentile for BMI by age/sex using Centers for Disease Control and Prevention growth charts. Child obesity prevalence significantly decreased between 2000-2002 and 2004-2005 for 4th grade students in the El Paso HSR (-7.0%, P = 0.005). A leveling off in the prevalence of obesity was noted for all other regions for grades 4, 8, and 11. County-level data supported the statistically significant decreases noted in the El Paso region. The reduction of child obesity levels observed in the El Paso area is one of the few examples of effective programs and policies based on a population-wide survey: in this region, a local foundation funded extensive regional implementation of community programs for obesity prevention, including an evidence-based elementary school-based health promotion program, adult nutrition and physical activity programs, and a radio and television advertising campaign. Results emphasize the need for sustained school, community, and policy efforts, and that these efforts can result in decreases in child obesity at the population level. PMID:19798066

  16. The incidence and risk factors of resistant E. coli infections after prostate biopsy under fluoroquinolone prophylaxis: a single-centre experience with 2215 patients.

    PubMed

    Kandemir, Özlem; Bozlu, Murat; Efesoy, Ozan; Güntekin, Onur; Tek, Mesut; Akbay, Erdem

    2016-08-01

    We evaluated the incidence and risk factors of resistant Escherichia coli infections after the prostate biopsy under flouroquinolone prophylaxis. From January 2003 to December 2012, we retrospectively evaluated the records of 2215 patients. The risk factors were described for infective complications and resistant E. coli in positive cultures was calculated. Of 2215 patients, 153 had positive urine cultures, such as 129 (84·3%) E. coli, 8 (5·2%) Enterococcus spp., 6 (3·9%) Enterobacter spp., 5 (3·2%) Pseudomonas spp., 3 (1·9%) MRCNS, and 2 (1·3%) Klebsiella spp. Of the positive urine cultures which yielded E. coli, 99 (76·7%) were evaluated for fluoroquinolone resistance. Of those, 83 (83·8%) were fluoroquinolone-resistant and composed of 51 (61·4%) extended-spectrum beta-lactamase (ESBL)-positive. Fluoroquinolone-resistant E. coli ratios were 73·4 and 95·9% before 2008 and after 2008, respectively (P = 0·002). The most sensitive antibiotics for fluoroquinolone-resistant E. coli strains were imipenem (100%), amikacin (84%) and cefoperazone (83%). The use of quinolones in the last 6 months and a history of hospitalization in the last 30 days were found to be significant risk factors. We found that resistant E. coli strains might be a common microorganism in patients with this kind of complication. The risk factors for development of infection with these resistant strains were history of the use of fluoroquinolones and hospitalization.

  17. Overexpression of patA and patB, Which Encode ABC Transporters, Is Associated with Fluoroquinolone Resistance in Clinical Isolates of Streptococcus pneumoniae▿

    PubMed Central

    Garvey, Mark I.; Baylay, Alison J.; Wong, Ryan L.; Piddock, Laura J. V.

    2011-01-01

    Fifty-seven clinical isolates of Streptococcus pneumoniae were divided into four groups based on their susceptibilities to the fluoroquinolones ciprofloxacin and norfloxacin and the dyes ethidium bromide and acriflavine. Comparative reverse transcription-PCR was used to determine the level of expression of the genes patA and patB, which encode putative ABC transporters. Overexpression was observed in 14 of the 15 isolates that were resistant to both fluoroquinolones and dyes and in only 3 of 24 of those resistant to fluoroquinolones only. Isolates overexpressing patA and patB accumulated significantly less of the fluorescent dye Hoechst 33342 than wild-type isolates, suggesting that PatA and PatB are involved in efflux. Inactivation of patA and patB by in vitro mariner mutagenesis conferred hypersusceptibility to ethidium bromide and acriflavine in all isolates tested and lowered the MICs of ciprofloxacin in the patAB-overproducing and/or fluoroquinolone-resistant isolates. These data represent the first observation of overexpression of patA and patB in clinical isolates and show that PatA and PatB play a clinically relevant role in fluoroquinolone resistance. PMID:20937787

  18. Resistance Mutations in gyrA and parC are Common in Escherichia Communities of both Fluoroquinolone-Polluted and Uncontaminated Aquatic Environments

    PubMed Central

    Johnning, Anna; Kristiansson, Erik; Fick, Jerker; Weijdegård, Birgitta; Larsson, D. G. Joakim

    2015-01-01

    Alterations in the target proteins of fluoroquinolones, especially in GyrA and ParC, are known to cause resistance. Here, we investigated environmental Escherichia communities to explore the possible link between the abundance of mutations, and the exposure to fluoroquinolones. Sediment samples were collected from a relatively pristine lake, up and downstream from a sewage treatment plant, and from several industrially polluted sites. The quinolone resistance-determining regions of gyrA and parC were analyzed using amplicon sequencing of metagenomic DNA. Five non-synonymous substitutions were present in all samples, and all of these mutations have been previously linked to fluoroquinolone resistance in Escherichia coli. In GyrA, substitutions S83L and D87N were on average detected at frequencies of 86 and 32%, respectively, and 31% of all amplicons encoded both substitutions. In ParC, substitutions S80I, E84G, and E84V were detected in 42, 0.9, and 6.0% of the amplicons, respectively, and 6.5% encoded double substitutions. There was no significant correlation between the level of fluoroquinolone pollution and the relative abundance of resistance mutations, with the exception of the most polluted site, which showed the highest abundance of said substitutions in both genes. Our results demonstrate that resistance mutations can be common in environmental Escherichia, even in the absence of a fluoroquinolone selective pressure. PMID:26696975

  19. The incidence and risk factors of resistant E. coli infections after prostate biopsy under fluoroquinolone prophylaxis: a single-centre experience with 2215 patients.

    PubMed

    Kandemir, Özlem; Bozlu, Murat; Efesoy, Ozan; Güntekin, Onur; Tek, Mesut; Akbay, Erdem

    2016-08-01

    We evaluated the incidence and risk factors of resistant Escherichia coli infections after the prostate biopsy under flouroquinolone prophylaxis. From January 2003 to December 2012, we retrospectively evaluated the records of 2215 patients. The risk factors were described for infective complications and resistant E. coli in positive cultures was calculated. Of 2215 patients, 153 had positive urine cultures, such as 129 (84·3%) E. coli, 8 (5·2%) Enterococcus spp., 6 (3·9%) Enterobacter spp., 5 (3·2%) Pseudomonas spp., 3 (1·9%) MRCNS, and 2 (1·3%) Klebsiella spp. Of the positive urine cultures which yielded E. coli, 99 (76·7%) were evaluated for fluoroquinolone resistance. Of those, 83 (83·8%) were fluoroquinolone-resistant and composed of 51 (61·4%) extended-spectrum beta-lactamase (ESBL)-positive. Fluoroquinolone-resistant E. coli ratios were 73·4 and 95·9% before 2008 and after 2008, respectively (P = 0·002). The most sensitive antibiotics for fluoroquinolone-resistant E. coli strains were imipenem (100%), amikacin (84%) and cefoperazone (83%). The use of quinolones in the last 6 months and a history of hospitalization in the last 30 days were found to be significant risk factors. We found that resistant E. coli strains might be a common microorganism in patients with this kind of complication. The risk factors for development of infection with these resistant strains were history of the use of fluoroquinolones and hospitalization. PMID:25630553

  20. How Do 4th, 5th, and 6th Grade Students' Categories of Cognitive Reflections in Interviews on Derivational Morphology Compare to Their Upper Level Spelling Inventory Orthographic Knowledge?

    ERIC Educational Resources Information Center

    Smith, Darcie D.

    2012-01-01

    Eighty-seven 4th, 5th and 6th grade students were administered the "Derivational Relatedness Interview" (DRI) (Templeton, Smith, Moloney, Van Pelt, & Ives, 2009). The purpose of this instrument is to explore students' understanding of derivational morphology. During the same week, the subjects were also administered an Upper…

  1. Degradation of fluoroquinolone antibiotics by ferrate(VI): Effects of water constituents and oxidized products.

    PubMed

    Feng, Mingbao; Wang, Xinghao; Chen, Jing; Qu, Ruijuan; Sui, Yunxia; Cizmas, Leslie; Wang, Zunyao; Sharma, Virender K

    2016-10-15

    The degradation of five fluoroquinolone (FQ) antibiotics (flumequine (FLU), enrofloxacin (ENR), norfloxacin (NOR), ofloxacin (OFL) and marbofloxacin (MAR)) by ferrate(VI) (Fe(VI)O4(2-), Fe(VI)) was examined to demonstrate the potential of this iron-based chemical oxidant to treat antibiotics in water. Experiments were conducted at different molar ratios of Fe(VI) to FQs at pH 7.0. All FQs, except FLU, were degraded within 2 min at [Fe(VI)]:[FQ] ≤ 20.0. Multiple additions of Fe(VI) improved the degradation efficiency, and provided greater degradation than a single addition of Fe(VI). The effects of anions, cations, and humic acid (HA), usually present in source waters and wastewaters, on the removal of FLU were investigated. Anions (Cl(-), SO4(2-), NO3(-), and HCO3(-)) and monovalent cations (Na(+) and K(+)) had no influence on the removal of FLU. However, multivalent cations (Ca(2+), Mg(2+), Cu(2+), and Fe(3+)) in water decreased the efficiency of FLU removal by Fe(VI). An increase in the ionic strength of the solution, and the presence of HA in the water, also decreased the percentage of FLU removed by Fe(VI). Experiments on the removal of selected FQs, present as co-existing antibiotics in pure water, river water, synthetic water and wastewater, were also conducted to demonstrate the practical application of Fe(VI) to remove the antibiotics during water treatment. The seventeen oxidized products (OPs) of FLU were identified using solid phase extraction-liquid chromatography-high-resolution mass spectrometry. The reaction pathways are proposed, and are theoretically confirmed by molecular orbital calculations.

  2. Portable surface plasmon resonance immunosensor for the detection of fluoroquinolone antibiotic residues in milk.

    PubMed

    Fernández, Fátima; Pinacho, Daniel G; Sánchez-Baeza, Francisco; Marco, M Pilar

    2011-05-11

    An inexpensive and portable surface plasmon resonance (SPR) sensor, SPReeta Evaluation Kit SPR3, has been used to develop a biosensor for the determination of fluoroquinolone antibiotics (FQs) and to demonstrate its performance analyzing FQ residues in milk samples. The SPReeta three-channel gold chips were activated with a mixed self-assembled monolayer (m-SAM) and functionalized with a FQ haptenized protein. Binding of the antibody produced a concentration-dependent increase of the SPR signal as a result of the change in the refraction index. Similarly, the presence of the FQ produced a dose-dependent decrease of the response, which allowed a good limit of detection (LOD) to be obtained (1.0 ± 0.4 μg L(-1) for enrofloxacin in buffer). The response was reproducible in all three channels, on different injections and days, and also between chips. Milk samples could be analyzed after a simple sample treatment involving fat removal by centrifugation and dilution with water. Under these conditions calibration curves were obtained showing that FQ residues can be analyzed in milk samples with an IC(50) value of 26.4 ± 7.2 μg L(-1) and a LOD of 2.0 ± 0.2 μg L(-1) (for enrofloxacin), far below the European Union regulations for this antibiotic family in this matrix. Finally, the paper also demonstrates that the biosensor is able to selectively detect the presence of FQs in milk samples, even in the presence of other antibiotics. Enrofloxacin, ciprofloxacin, and norfloxacin residues were detected in blind samples supplied by Nestlé Co. PMID:21476576

  3. Adsorption of zwitterionic fluoroquinolone antibacterials to goethite: a charge distribution-multisite complexation model.

    PubMed

    Paul, Tias; Liu, Jinyong; Machesky, Michael L; Strathmann, Timothy J

    2014-08-15

    Fluoroquinolone (FQ) antibacterials are aquatic contaminants of emerging concern (CEC), and adsorption to mineral surfaces is expected to play an important role in the fate, transport, and treatment of FQs. This study characterizes and models the adsorption of a zwitterionic FQ, ofloxacin (OFX), to goethite (α-FeOOH) over a wide range of pH (3-11), OFX concentration (20-500 μM), and electrolyte compositions (0.001-0.1M NaCl and NaClO4). Comparing OFX adsorption to structural analogues demonstrates that the carboxylate group is essential for binding to goethite. ATR-FTIR measurements indicate that FQs complex to goethite surfaces through carboxylate and carbonyl oxygen atoms, and that ClO4(-) co-adsorbs with OFX. Adsorption of the zwitterionic OFX increases with increasing ionic strength and is enhanced in NaClO4 relative to NaCl electrolyte, whereas adsorption of a non-zwitterionic analogue is insensitive to ionic strength. A CD-MUSIC (charge distribution-multisite complexation) model, incorporating multiple modes of surface complexation constrained by spectroscopic measurements and the crystallographic distribution of goethite surface sites, yields accurate predictions over wide-ranging solution conditions. According to the model, OFX adsorbs predominantly by inner-sphere complexation on terminal surfaces of the rod-shaped goethite crystals in NaCl electrolyte, and OFX-ClO4(-) ion pairing in NaClO4 induces formation of additional inner- and outer-sphere surface complexes on multiple crystal faces of goethite.

  4. Effects of Fluoroquinolones and Azithromycin on Biofilm Formation of Stenotrophomonas maltophilia

    PubMed Central

    Wang, Aihua; Wang, Qinqin; Kudinha, Timothy; Xiao, Shunian; Zhuo, Chao

    2016-01-01

    Stenotrophomonas maltophilia is an opportunistic pathogen that causes respiratory and urinary tract infections, as well as wound infections in immunocompromised patients. This pathogen is difficult to treat due to increased resistance to many antimicrobial agents. We investigated the in vitro biofilm formation of S. maltophilia, including effects of fluoroquinolones (FQs) and azithromycin on biofilm formation. The organism initiated attachment to polystyrene surfaces after a 4 h incubation period, and reached maximal growth at 18–24 h. In the presence of FQs (moxifloxacin, levofloxacin or ciprofloxacin), the biofilm biomass was significantly reduced (P < 0.05). A lower concentration of moxifloxacin (10 μg/mL) exhibited a better inhibiting effect on biofilm formation than 100 μg/mL (P < 0.01), but with no difference in effect compared to the 50 μg/mL concentration (P > 0.05). However, the inhibitory effects of 10 μg/mL of levofloxacin or ciprofloxacin were slightly less pronounced than those of the higher concentrations. A combination of azithromycin and FQs significantly reduced the biofilm inhibiting effect on S. maltophilia preformed biofilms compared to azithromycin or FQs alone. We conclude that early use of clinically acceptable concentrations of FQs, especially moxifloxacin (10 μg/mL), may possibly inhibit biofilm formation by S. maltophilia. Our study provides an experimental basis for a possible optimal treatment strategy for S. maltophilia biofilm-related infections. PMID:27405358

  5. Spectroscopic studies on the lanthanide sensitized luminescence and chemiluminescence properties of fluoroquinolone with different structure

    NASA Astrophysics Data System (ADS)

    Sun, Chunyan; Ping, Hong; Zhang, Minwei; Li, Hongkun; Guan, Fengrui

    2011-11-01

    Lanthanide sensitized luminescence and chemiluminescence (CL) are of great importance because of the unique spectral properties, such as long lifetime, large Stokes shifts, and narrow emission bands characteristic to lanthanide ions (Ln 3+). With the fluoroquinolone (FQ) compounds including enoxacin (ENX), norfloxacin (NFLX), lomefloxacin (LMFX), fleroxacin (FLRX), ofloxacin (OFLX), rufloxacin (RFX), gatifloxacin (GFLX) and sparfloxacin (SPFX), the luminescence and CL properties of Tb 3+-FQ and Eu 3+-FQ complexes have been investigated in this contribution. Ce 4+-SO 32- in acidic conditions was taken as the CL system and sensitized CL intensities of Tb 3+-FQ and Eu 3+-FQ complexes were determined by flow-injection analysis. The luminescence and CL spectra of Tb 3+-FQ complexes show characteristic peaks of Tb 3+ at 490 nm, 545 nm, 585 nm and 620 nm. Complexes of Tb 3+-ENX, Tb 3+-NFLX, Tb 3+-LMFX and Tb 3+-FLRX display relatively strong emission intensity compared with Tb 3+-OFLX, Tb 3+-RFX, Tb 3+-GFLX and Tb 3+-SPFX. Quite weak peaks with unique characters of Eu 3+ at 590 nm and 617 nm appear in the luminescence and CL spectra of Eu 3+-ENX, but no notable sensitized luminescence and CL of Eu 3+ could be observed when Eu 3+ is added into other FQ. The distinct differences on emission intensity of Tb 3+-FQ and Eu 3+-FQ might originate from the different energy gap between the triplet levels of FQ and the excited levels of the Ln 3+. The different sensitized luminescence and CL signals among Tb 3+-FQ complexes could be attributed to different optical properties and substituents of these FQ compounds. The detailed mechanism involved in the luminescence and CL properties of Tb 3+-FQ and Eu 3+-FQ complexes has been investigated by analyzing the luminescence and CL spectra, quantum yields, and theoretical calculation results.

  6. Antimicrobial resistance and genetic characterization of fluoroquinolone resistance of Pseudomonas aeruginosa isolated from canine infections.

    PubMed

    Rubin, J; Walker, R D; Blickenstaff, K; Bodeis-Jones, S; Zhao, S

    2008-09-18

    Infections with antimicrobial-resistant bacteria are a great challenge in both human and veterinary medicine. The purpose of this study was to determine antimicrobial susceptibility of 106 strains of Pseudomonas aeruginosa isolated from dogs with otitis and pyoderma from 2003 to 2006 in the United States. Three antimicrobial panels, including 6 classes and 32 antimicrobial agents, were used. A wide range of susceptibility patterns were noted with some isolates being resistant to between 8 and 28 (mean 16) of the antimicrobials tested. Among the beta-lactams, all isolates were resistant to ampicillin, cefoxitin, cefpodoxime, cephalothin and cefazolin followed by amoxicillin/clavulanic acid (99%), ceftiofur (97%), ceftriaxone (39%), cefotaxime (26%), and cefotaxime/clavulanic acid (20%), whereas less than 7% of isolates were resistant to ceftazidime/clavulanic acid, ceftazidime, piperacillin/tazobactam or cefepime. Two isolates were resistant to the carbapenems. Among the quinolones and fluoroquinolones, the most isolates were resistant to naladixic acid (96%), followed by orbifloxacin (52%), difloxacin (43%), enrofloxacin (31%), marbofloxacin (27%), gatifloxacin (23%), levofloxacin (21%), and ciprofloxacin (16%). Among the aminoglycosides, the most resistance was seen to kanamycin (90%), followed by streptomycin (69%), gentamicin (7%), and amikacin (3%). Of the remaining antimicrobials 100% of the isolates were resistant to chloramphenicol followed by tetracycline (98%), trimethoprim/sulfamethoxazole (57%), and sulfisoxazole (51%). Point mutations were present in gyrA, gyrB, parC, and/or parE genes among 34 of the 102 naladixic acid-resistant isolates. Two isolates contained class 1 integrons carrying aadA gene conferring streptomycin and spectinomycin resistance. The findings suggest that many antimicrobial agents commonly used in companion animals may not constitute appropriate therapy for canine pseudomonas infections.

  7. Treatment Outcomes with Fluoroquinolone-Containing Regimens for Isoniazid-Resistant Pulmonary Tuberculosis

    PubMed Central

    Lee, Hyun; Jeong, Byeong-Ho; Park, Hye Yun; Jeon, Kyeongman; Huh, Hee Jae; Lee, Nam Yong

    2015-01-01

    Resistance to isoniazid (INH) is the most common form of drug resistance in pulmonary tuberculosis (TB). Although fluoroquinolones (FQs) are recommended to strengthen treatment regimens for INH-resistant pulmonary TB, few studies have evaluated the clinical efficacy of FQ-containing regimens in patients with INH-resistant pulmonary TB. A retrospective cohort study of 140 patients with INH-resistant pulmonary TB was performed between 2005 and 2012. We evaluated whether FQ-containing regimens yielded improved treatment outcomes for patients with INH-resistant pulmonary TB. Overall, favorable outcomes were achieved in 128 (91.4%) patients. Unfavorable outcomes occurred in 12 patients (8.6%), including 7 with treatment failure (5.0%) and 5 with relapse after initial treatment completion (3.6%). FQs, such as levofloxacin and moxifloxacin, were given to 75 (53.6%) patients. Favorable treatment outcomes were more frequent for patients who received FQs (97.3% [73/75 patients]) than for those who did not receive FQs (84.6% [55/65 patients]) (P = 0.007). Patients who did not receive FQs were more likely to develop treatment failure (9.2% [6/65 patients] versus 1.3% [1/75 patients]) (P = 0.049) than patients who received FQs. The adjusted proportion of unfavorable outcomes was significantly higher among patients who did not receive FQs (8.8%; 95% confidence interval [CI], 3.3 to 21.5%) than among those who did receive FQs (1.5%; 95% CI, 0.3 to 7.7%) (P = 0.037). These results suggest that the addition of FQs can improve treatment outcomes for patients with INH-resistant pulmonary TB. PMID:26525801

  8. Degradation of the fluoroquinolone enrofloxacin by the brown rot fungus Gloeophyllum striatum: identification of metabolites.

    PubMed Central

    Wetzstein, H G; Schmeer, N; Karl, W

    1997-01-01

    The degradation of enrofloxacin, a fluoroquinolone antibacterial drug used in veterinary medicine, was investigated with the brown rot fungus Gloeophyllum striatum. After 8 weeks, mycelia suspended in a defined liquid medium had produced 27.3, 18.5, and 6.7% 14CO2 from [14C]enrofloxacin labeled either at position C-2, at position C-4, or in the piperazinyl moiety, respectively. Enrofloxacin, applied at 10 ppm, was transformed into metabolites already after about 1 week. The most stable intermediates present in 2-day-old supernatants were analyzed by high-performance liquid chromatography combined with electrospray ionization mass spectrometry. Eight of 11 proposed molecular structures could be confirmed by 1H nuclear magnetic resonance spectroscopy or by cochromatography with reference compounds. We identified (i) 3-, 6-, and 8-hydroxylated congeners of enrofloxacin, which have no or only very little residual antibacterial activity; (ii) 5,6- (or 6,8-), 5,8-, and 7,8-dihydroxylated congeners, which were prone to autoxidative transformation; (iii) an isatin-type compound as well as an anthranilic acid derivative, directly demonstrating cleavage of the heterocyclic core of enrofloxacin; and (iv) 1-ethylpiperazine, the 7-amino congener, and desethylene-enrofloxacin, representing both elimination and degradation of the piperazinyl moiety. The pattern of metabolites implies four principle routes of degradation which might be simultaneously employed. Each route, initiated by either oxidative decarboxylation, defluorination, hydroxylation at C-8, or oxidation of the piperazinyl moiety, may reflect an initial attack by hydroxyl radicals at a different site of the drug. During chemical degradation of [4-14C]enrofloxacin with Fenton's reagent, five confirmatory metabolites, contained in groups i and iv, were identified. These findings provide new evidence in support of the hypothesis that brown rot fungi may be capable of producing hydroxyl radicals, which could be utilized

  9. Fluoroquinolone resistance of Serratia marcescens: sucrose, salicylate, temperature, and pH induction of phenotypic resistance.

    PubMed

    Begic, Sanela; Worobec, Elizabeth A

    2007-11-01

    Serratia marcescens is a nosocomial agent with a natural resistance to a broad spectrum of antibiotics, making the treatment of its infections very challenging. This study examines the influence of salicylate, sucrose, temperature, and pH variability on membrane permeability and susceptibility of S. marcescens to norfloxacin (hydrophilic fluoroquinolone) and nalidixic acid (hydrophobic quinolone). Resistance of wild-type S. marcescens UOC-67 (ATCC 13880) to norfloxacin and nalidixic acid was assessed by minimal inhibitory concentration (MIC) assays after growth in the presence of various concentrations of sucrose and salicylate and different temperatures and pH values. Norfloxacin and nalidixic acid accumulation was determined in the absence and presence of (i) carbonyl cyanide m-chlorophenylhydrazone (CCCP), a proton-motive-force collapser, and (ii) Phe-Arg beta-naphthylamide (PAbetaN), an efflux pump inhibitor. Accumulation of norfloxacin decreased when S. marcescens was grown in high concentrations of salicylate (8 mmol/L) and sucrose (10% m/v), at high temperature (42 degrees C), and at pH 6, and it was restored in the presence of CCCP because of the collapse of proton-gradient-dependent efflux in S. marcescens. Although nalidixic acid accumulation was observed, it was not affected by salicylate, sucrose, pH, or temperature changes. In the absence of PAbetaN, and either in the presence or absence of CCCP, a plateau was reached in the nalidixic acid accumulation for all environmental conditions. With the addition of 20 mg/L PAbetaN nalidixic acid accumulation is restored for all environmental conditions, suggesting that this quinolone is recognized by a yet to be identified S. marcescens pump that does not use proton motive force as its energy source.

  10. Effect of Ethanol on Fluoroquinolone Efficacy in a Rat Model of Pneumococcal Pneumonia

    PubMed Central

    Olsen, Keith M.; Gentry-Nielsen, Martha; Yue, Mei; Snitily, Mary U.; Preheim, Laurel C.

    2006-01-01

    This investigation compared the effect of ethanol on fluoroquinolone antibiotic efficacy and pharmacodynamics in an ethanol-fed rat model of pneumococcal pneumonia. Male Sprague-Dawley rats received a liquid diet containing 36% of total calories as ethanol. Paired controls (pair-fed controls) were fed a liquid diet without ethanol or received rat chow. Diets began 7 days before and continued for 10 days after transtracheal infections with 10 times the 50% lethal dose of type 3 Streptococcus pneumoniae. Beginning 18 h after infection, the rats received once daily subcutaneous phosphate-buffered saline, levofloxacin, moxifloxacin, or trovafloxacin at 50 or 100 mg/kg of body weight. White blood cell counts were determined, blood samples were collected for culture, and mortality was recorded. Additional rats were killed on day 5 for pharmacodynamic studies and quantitative cultures of bronchoalveolar lavage fluid. Bacteremia occurred by day 3 in 20 of 22 untreated rats. All 22 untreated rats died by day 9. Moxifloxacin treatment was effective in all diet groups at both the 50- and 100-mg/kg doses. In contrast, 50-mg/kg doses of levofloxacin and trovafloxacin improved survival in ethanol-fed rats but were ineffective in chow-fed rats. High-dose trovafloxacin at 100 mg/kg was associated with increased mortality in pair-fed rats. The free-fraction area under the concentration-time curve/MIC ratio exceeded 50 with all antibiotics in the ethanol group but dropped below 30 with levofloxacin and trovafloxacin in the pair- and chow-fed rats, with higher mortality. Achievement of adequate antibiotic-free fraction area under the concentration-time curve/MIC ratios helps overcome ethanol-induced immune defects induced in experimental pneumococcal pneumonia. PMID:16377688

  11. Degradation of fluoroquinolone antibiotics by ferrate(VI): Effects of water constituents and oxidized products.

    PubMed

    Feng, Mingbao; Wang, Xinghao; Chen, Jing; Qu, Ruijuan; Sui, Yunxia; Cizmas, Leslie; Wang, Zunyao; Sharma, Virender K

    2016-10-15

    The degradation of five fluoroquinolone (FQ) antibiotics (flumequine (FLU), enrofloxacin (ENR), norfloxacin (NOR), ofloxacin (OFL) and marbofloxacin (MAR)) by ferrate(VI) (Fe(VI)O4(2-), Fe(VI)) was examined to demonstrate the potential of this iron-based chemical oxidant to treat antibiotics in water. Experiments were conducted at different molar ratios of Fe(VI) to FQs at pH 7.0. All FQs, except FLU, were degraded within 2 min at [Fe(VI)]:[FQ] ≤ 20.0. Multiple additions of Fe(VI) improved the degradation efficiency, and provided greater degradation than a single addition of Fe(VI). The effects of anions, cations, and humic acid (HA), usually present in source waters and wastewaters, on the removal of FLU were investigated. Anions (Cl(-), SO4(2-), NO3(-), and HCO3(-)) and monovalent cations (Na(+) and K(+)) had no influence on the removal of FLU. However, multivalent cations (Ca(2+), Mg(2+), Cu(2+), and Fe(3+)) in water decreased the efficiency of FLU removal by Fe(VI). An increase in the ionic strength of the solution, and the presence of HA in the water, also decreased the percentage of FLU removed by Fe(VI). Experiments on the removal of selected FQs, present as co-existing antibiotics in pure water, river water, synthetic water and wastewater, were also conducted to demonstrate the practical application of Fe(VI) to remove the antibiotics during water treatment. The seventeen oxidized products (OPs) of FLU were identified using solid phase extraction-liquid chromatography-high-resolution mass spectrometry. The reaction pathways are proposed, and are theoretically confirmed by molecular orbital calculations. PMID:27429354

  12. Proteoglycan and Collagen Biochemical Variations during Fluoroquinolone-Induced Chondrotoxicity in Mice

    PubMed Central

    Simonin, Marie-Agnès; Gegout-Pottie, Pascale; Minn, Alain; Gillet, Pierre; Netter, Patrick; Terlain, Bernard

    1999-01-01

    Although fluoroquinolone antibacterials have a broad therapeutic use, with a relatively low incidence of severe side effects, they have been reported to induce lesions in the cartilage of growing animals by a mechanism that remains unclear. This study was undertaken to determine the potentially deleterious effect of a high dose of pefloxacin (400 mg/kg of body weight) on two main constituents of cartilage in mice, i.e., proteoglycans and collagen. Variations in levels of proteoglycan anabolism measured by in vivo [35S]sulfate incorporation into cartilage and oxidative modifications of collagen assessed by detection of carbonyl derivatives were monitored after administration of pefloxacin. Treatment of mice with 1 day of pefloxacin treatment significantly decreased the rate of biosynthesis of proteoglycan for the first 24 h. However, no difference was observed after 48 h. The decrease in proteoglycan synthesis was accompanied by a marked drop in serum sulfate concentration and a concomitant increase in urinary sulfate excretion. The decrease in proteoglycan synthesis, also observed ex vivo, may suggest a direct effect of pefloxacin on this process, rather than it being a consequence of a low concentration of sulfate. On the other hand, treatment with pefloxacin for 10 days induced oxidative damage to collagen. In conclusion, this study demonstrates, for the first time, that pefloxacin administration to mice leads to modifications in the metabolism and integrity of extracellular proteins, such as collagen and proteoglycans, which may account for the side effects observed. These results offer new insights to explain quinolone-induced disorders in growing articular cartilage. PMID:10582882

  13. A new approach to quantitative NMR: fluoroquinolones analysis by evaluating the chemical shift displacements.

    PubMed

    Michaleas, S; Antoniadou-Vyza, E

    2006-10-11

    Quantitative NMR spectroscopy is always an attractive goal as the identity and quantity could be simultaneously determined. Although significant advancements have been achieved in this field it is common that all reported quantitative NMR methods perform the analysis by utilizing the average integral intensities of selected signals. During the calculation of the area under NMR peaks several response problems can occur which should always be treated carefully to overcome inaccuracies. In the method proposed in this work the quantitative information is obtained utilizing the measurement of selected protons chemical shift displacements which is a quite straightforward and highly reproducible process. The (1)H NMR spectra of multiple fluoroquinolone (FQ) solutions revealed that the chemical shifts of protons, especially the aromatic ones, were concentration dependent for all tested compounds, as a result of extensive self-association phenomena. In the present work a novel methodology is described for the quantitation of several FQs based on this dependence. The proposed method was applied to Ciprofloxacin solutions over a wide range of concentrations. Evaluation of the obtained data presented acceptable characteristics regarding accuracy, precision, and robustness. The applicability limitations of this method were found to be posed by current instrumentation, mainly by the magnetic field frequency e.g. the slope of the response function achieved with a 400MHz instrument was twice the one achieved at 200MHz. The pH effect was negligible from pD 2.5 to 5.5. The phenomenon appeared in a pattern that can be applied for a plethora of drug categories revealing self-association phenomena in a range of concentration determined by the magnet strength of the instrument.

  14. Fluoroquinolones and Tetracycline Antibiotics in a Portuguese Aquaculture System and Aquatic Surroundings: Occurrence and Environmental Impact.

    PubMed

    Pereira, André M P T; Silva, Liliana J G; Meisel, Leonor M; Pena, Angelina

    2015-01-01

    The growth of aquaculture over the past few years is widely recognized as one of the main sources of antibiotics, mainly fluoroquinolones (FQ) and tetracyclines (TC), in the aquatic environment, consequently, increasing the risk of the emergence of antibiotic bacterial resistance and promoting the spread of resistant genes. This study aimed to (1) develop and validate a multiresidue method for determination and quantification of ciprofloxacin (CIP), difloxacin (DIFL), enrofloxacin (ENR), norfloxacin (NOR), sarafloxacin (SARA), and oxytetracycline (OXY) in aquaculture waters and surrounding water bodies and (2) provide the first Portuguese data to utilize in assessment of risk of adverse effects. In addition, the potential environmental impact posed by these antibiotics to aquatic organisms, belonging to different trophic levels, when exposed to the studied aquaculture waters was also assessed. The analytical strategy comprised of solid-phase extraction (SPE) through Oasis HLB cartridges, and detection and quantification by liquid chromatography with tandem mass spectrometry (LC/MS(n)). Method detection limits (MDL) and method quantification limits (MQL) were in the range of 0.7-3 ng/L and 2.4-10 ng/L, respectively. Recoveries varied between 57.4 and 122.8%. The method was applied to 31 water samples collected from an aquaculture and surrounding water bodies located in north of Portugal. Residues of all antibiotics, except SARA and DIFL, were detected at concentrations ranging from 3 to 75.1 ng/L. Norfloxacin was the antibiotic present at highest frequency and concentration. Regarding the environmental impact assessment (EIA), a risk quotient higher than 1 was observed for NOR.

  15. Effect of Fluoroquinolones and Macrolides on Eradication and Resistance of Haemophilus influenzae in Chronic Obstructive Pulmonary Disease.

    PubMed

    Pettigrew, Melinda M; Tsuji, Brian T; Gent, Janneane F; Kong, Yong; Holden, Patricia N; Sethi, Sanjay; Murphy, Timothy F

    2016-07-01

    Little is known about the effect of antibiotics on eradication of carriage and development of resistance in Haemophilus influenzae in individuals with chronic obstructive pulmonary disease (COPD). Our goals were to assess antibiotic susceptibilities, prevalence of resistance genes, and development of resistance in H. influenzae and to evaluate the effect of macrolide and fluoroquinolone administration on H. influenzae eradication. Data were from a 15-year longitudinal study of COPD. Genome sequence data were used to determine genotype and identify resistance genes. MICs of antibiotics were determined by reference broth microdilution. Generalized linear mixed models were used to evaluate associations between antibiotic use and H. influenzae eradication. We examined 267 H. influenzae isolates from 77 individuals. All newly acquired H. influenzae isolates were susceptible to azithromycin. Five of 27 (19%) strains developed 4-fold increases in azithromycin MICs and reached or exceeded the susceptibility breakpoint (≤4 μg/ml) during exposure. H. influenzae isolates were uniformly susceptible to ciprofloxacin, levofloxacin, and moxifloxacin (MIC90s of 0.015, 0.015, and 0.06, respectively); there were no mutations in quinolone resistance-determining regions. Fluoroquinolone administration was associated with increased H. influenzae eradication compared to macrolides (odds ratio [OR], 16.67; 95% confidence interval [CI], 2.67 to 104.09). There was no difference in H. influenzae eradication when comparing macrolide administration to no antibiotic (OR, 1.89; 95% CI, 0.43 to 8.30). Fluoroquinolones are effective in eradicating H. influenzae in individuals with COPD. Macrolides are ineffective in eradicating H. influenzae, and their use in COPD patients may lead to decreased macrolide susceptibility and resistance.

  16. Simultaneous determination of 13 fluoroquinolone and 22 sulfonamide residues in milk by a dual-colorimetric enzyme-linked immunosorbent assay.

    PubMed

    Jiang, Wenxiao; Wang, Zhanhui; Beier, Ross C; Jiang, Haiyang; Wu, Yongning; Shen, Jianzhong

    2013-02-19

    Enzyme-linked immunosorbent assays (ELISAs) usually focus on the detection of a single analyte or a single group of analytes, e.g., fluoroquinolones or sulfonamides. However, it is often necessary to simultaneously monitor two classes of antimicrobial residues in different food matrixes. In this paper, we describe a dual-colorimetric ELISA for the simultaneous detection of 13 fluoroquinolone and 22 sulfonamide residues. The limit of detection for fluoroquinolones and sulfonamides was 2.4 and 5.8 ng/mL, respectively. The developed immunoassay is suitable for high-throughput screening of these low-molecular weight contaminants. This is the first report where two different enzymes (alkaline phosphatase and horseradish peroxidase) were used in one immunoassay and together in a single well for simultaneous detection of multiple low-molecular weight chemical residues.

  17. New Wisdom to Defy an Old Enemy: Summary from a scientific symposium at the 4th Influenza Vaccines for the World (IVW) 2012 Congress, 11 October, Valencia, Spain.

    PubMed

    Poland, Gregory A; Fleming, Douglas M; Treanor, John J; Maraskovsky, Eugene; Luke, Thomas C; Ball, Emma M A; Poland, Caroline M

    2013-04-17

    Both seasonal and pandemic influenza cause considerable morbidity and mortality globally. In addition, the ongoing threat of new, unpredictable influenza pandemics from emerging variant strains cannot be underestimated. Recently bioCSL (previously known as CSL Biotherapies) sponsored a symposium 'New Wisdom to Defy an Old Enemy' at the 4th Influenza Vaccines for the World Congress in Valencia, Spain. This symposium brought together a renowned faculty of experts to discuss lessons from past experience, novel influenza vaccine developments, and new methods to increase vaccine acceptance and coverage. Specific topics reviewed and discussed included new vaccine development efforts focused on improving efficacy via alternative administration routes, dose modifications, improved adjuvants, and the use of master donor viruses. Improved safety was also discussed, particularly the new finding of an excess of febrile reactions isolated to children who received the 2010 Southern Hemisphere (SH) trivalent inactivated influenza vaccine (TIV). Significant work has been done to both identify the cause and minimize the risk of febrile reactions in children. Other novel prophylactic and therapeutic advances were discussed including immunotherapy. Standard IVIg and hIVIg have been used in ferret studies and human case reports with promising results. New adjuvants, such as ISCOMATRIX™ adjuvant, were noted to provide single-dose, prolonged protection with seasonal vaccine after lethal H5N1 virus challenge in a ferret model of human influenza disease. The data suggest that adjuvanted seasonal influenza vaccines may provide broader protection than unadjuvanted vaccines. The use of an antigen-formulated vaccine to induce broad protection between pandemics that could bridge the gap between pandemic declaration and the production of a homologous vaccine was also discussed. Finally, despite the availability of effective vaccines, most current efforts to increase influenza vaccine coverage

  18. EDITORIAL: Instrumentation and Methods for Neutron Scattering—papers from the 4th European Conference on Neutron Scattering in Lund, Sweden, June 2007

    NASA Astrophysics Data System (ADS)

    Rennie, Adrian R.

    2008-03-01

    Neutron scattering is used as a tool to study problems in disciplines that include chemistry, materials science, biology and condensed matter physics as well as problems from neighbouring disciplines such as geology, environmental sciences and archaeology. Equipment for these studies is found at laboratories with research reactors or spallation neutron sources and there are many recent or current developments with new instruments and even entirely new facilities such as the Spallation Neutron Source at Oak Ridge, USA, the OPAL reactor at Lucas Heights, Australia and the second target station at the ISIS facility in the UK. Design and optimization of the instruments at these facilities involves work with many research laboratories and groups in universities. Every four years the European Conference on Neutron Scattering (ECNS) brings together both the specialists in neutron instrumentation and the community of users (in intervening years there are International and American conferences). In June 2007 about 700 delegates came to the 4th ECNS that was held in Lund, Sweden. There were more than 600 presentations as talks and posters. The opportunity to publish papers in Measurement Science and Technology that relate to neutron scattering instrumentation and method development was offered to the participants, and the papers that follow describe some of the recent activity in this field. Accounts of work on condensed matter science and the applications of neutron scattering appear separately in Journal of Physics: Condensed Matter. There are, of course, many features of neutron instrumentation that are specific to this particular field of measurement. However, there are also many elements of apparatus and experiment design that can usefully be shared with a broader community. It is hoped that this issue with papers from ECNS will find a broad community of interest. Apart from descriptions of overall design of diffractometers and spectrometers there are accounts of new

  19. New Wisdom to Defy an Old Enemy: Summary from a scientific symposium at the 4th Influenza Vaccines for the World (IVW) 2012 Congress, 11 October, Valencia, Spain.

    PubMed

    Poland, Gregory A; Fleming, Douglas M; Treanor, John J; Maraskovsky, Eugene; Luke, Thomas C; Ball, Emma M A; Poland, Caroline M

    2013-04-17

    Both seasonal and pandemic influenza cause considerable morbidity and mortality globally. In addition, the ongoing threat of new, unpredictable influenza pandemics from emerging variant strains cannot be underestimated. Recently bioCSL (previously known as CSL Biotherapies) sponsored a symposium 'New Wisdom to Defy an Old Enemy' at the 4th Influenza Vaccines for the World Congress in Valencia, Spain. This symposium brought together a renowned faculty of experts to discuss lessons from past experience, novel influenza vaccine developments, and new methods to increase vaccine acceptance and coverage. Specific topics reviewed and discussed included new vaccine development efforts focused on improving efficacy via alternative administration routes, dose modifications, improved adjuvants, and the use of master donor viruses. Improved safety was also discussed, particularly the new finding of an excess of febrile reactions isolated to children who received the 2010 Southern Hemisphere (SH) trivalent inactivated influenza vaccine (TIV). Significant work has been done to both identify the cause and minimize the risk of febrile reactions in children. Other novel prophylactic and therapeutic advances were discussed including immunotherapy. Standard IVIg and hIVIg have been used in ferret studies and human case reports with promising results. New adjuvants, such as ISCOMATRIX™ adjuvant, were noted to provide single-dose, prolonged protection with seasonal vaccine after lethal H5N1 virus challenge in a ferret model of human influenza disease. The data suggest that adjuvanted seasonal influenza vaccines may provide broader protection than unadjuvanted vaccines. The use of an antigen-formulated vaccine to induce broad protection between pandemics that could bridge the gap between pandemic declaration and the production of a homologous vaccine was also discussed. Finally, despite the availability of effective vaccines, most current efforts to increase influenza vaccine coverage

  20. Genetic Characterization of Fluoroquinolone-Resistant Streptococcus pneumoniae Strains Isolated during Ciprofloxacin Therapy from a Patient with Bronchiectasis

    PubMed Central

    de la Campa, Adela G.; Ferrandiz, María-José; Tubau, Fe; Pallarés, Román; Manresa, Federico; Liñares, Josefina

    2003-01-01

    Five Spain9V-3 Streptococcus pneumoniae strains were isolated from a patient with bronchiectasis who had received long-term ciprofloxacin therapy. One ciprofloxacin-susceptible strain was isolated before treatment, and four ciprofloxacin-resistant strains were isolated during treatment. The resistant strains were derived from the susceptible strain either by a parC mutation (low-level resistance) or by parC and gyrA mutations (high-level resistance). This study shows that ciprofloxacin therapy in a patient colonized by susceptible S. pneumoniae may select fluoroquinolone-resistant mutants. PMID:12654682

  1. Fluoroquinolone and Ovariectomy in the Bitch: Physiology of the Immune System as to CD56 and CD16 Expression.

    PubMed

    Albrizio, Maria; Rizzo, Annalisa; Pantaleo, Marianna; Pampurini, Fabrizio; Piccinno, Mariagrazia; Sciorsci, Raffaele Luigi

    2015-01-01

    Natural killer (NK) cells are innate lymphoid cells which act against a variety of pathogens and tumours. Phenotypically they are characterized by surface markers named cluster designation (CD) antigens. CD56 and CD16 are recognized as specific NK markers in the dogs as well as in humans. Surgical interventions suppress NK cells both in rats and humans. In this direction, it has been shown that an antibiotic regimen (amoxicillin, benzylpenicillin/dihydrostreptomycin, sulfametazine/sulfamerazine/ sulfathiazole, enrofloxacin, lincomycin/spectinomycin) administered only twice is effective in preventing infections after laparatomic ovariectomy, in the bitch. On these grounds, this research will show that the administration of a fluoroquinolone (5 mg/kg of enrofloxacin, Baytril®, Bayer, Milan, Italy) one hour before and at the end of ovariectomy is able to increase CD56 and CD16 expression levels. Moreover, the antibiotic administration modifies the relative expression levels of the two CD; thus suggesting that the fluoroquinolone employed enhances the activation of a specific subset of NK cells mainly involved in body recovering during the post operative period as already observed in humans.

  2. Comparative activities of new fluoroquinolones, alone or in combination with amoxicillin, trimethoprim-sulfamethoxazole, or rifampin, against intracellular Listeria monocytogenes.

    PubMed Central

    Michelet, C; Avril, J L; Arvieux, C; Jacquelinet, C; Vu, N; Cartier, F

    1997-01-01

    We studied the activities of the new fluoroquinolones clinafloxacin, levofloxacin, ofloxacin, and sparfloxacin alone or in combination on the intracellular growth of Listeria monocytogenes. Against intracellular growth of the four strains tested, a similar reduction of the bacterial count was obtained with clinafloxacin at the dose of 10 x MIC (delta log10 CFU/ml = -2.19 +/- 0.24), with levofloxacin at 8 x MIC (delta log10 CFU/ml = -2.28 +/- 0.25), and with sparfloxacin at 4 x MIC (delta log10 CFU/ml = -2.16 +/- 0.21) after 24 h of incubation. The combination of the quinolones with trimethoprim-sulfamethoxazole or amoxicillin did not show a substantial increase in activity compared to the fluoroquinolone alone. Antagonism with rifampin was strongly suggested. No modification of the MIC was observed after 20 successive infections of HeLa cells and contact with subinhibitory concentrations of clinafloxacin, levofloxacin, and sparfloxacin for 24 h. We conclude that clinafloxacin, levofloxacin, or sparfloxacin could represent a therapeutic alternative to amoxicillin for the treatment of Listeria infections in adults, especially clinafloxacin, whose MIC is low (0.06 to 0.12 micrograms/ml), and whose best activity against intracellular L. monocytogenes was obtained at a concentration of 1.2 micrograms/ml, which is similar to clinically achievable levels. The results must be confirmed in an experimental model. PMID:8980755

  3. Horizontal Transfer of parC and gyrA in Fluoroquinolone-Resistant Clinical Isolates of Streptococcus pneumoniae

    PubMed Central

    Ferrándiz, María José; Fenoll, Asunción; Liñares, Josefina; De La Campa, Adela G.

    2000-01-01

    We have analyzed genetically three clinical isolates (3180, 3870, and 1244) of Streptococcus pneumoniae with high-level ciprofloxacin resistance. Isolates 3180 and 3870 were atypical because of their insolubility in deoxycholate. However, they hybridized specifically with pneumococcal autolysin and pneumolysin gene probes and have typical pneumococcal atpC and atpA gene sequences. Analysis of the complete sequences of the parC and gyrA genes revealed total variations of 8 and 8.7% (isolate 3180) and 7.4 and 3.6% (isolate 3870), respectively, compared to the wild-type strain R6 sequence. The variations observed between the sequences of R6 and isolate 1244 were less than 0.9%. The structure of the gyrA and parC genes from isolates 3180 and 3870 was organized in sequence blocks that show different levels of divergence, suggesting a pattern of recombination. These results are evidence for recombination at the fluoroquinolone target genes in clinical isolates of S. pneumoniae. The genetically related viridans group streptococci could act as a reservoir for fluoroquinolone resistance genes. PMID:10722479

  4. Single-step extraction followed by LC for determination of (fluoro)quinolone drug residues in muscle, eggs, and milk.

    PubMed

    Cho, Hee-Jung; Yi, Hee; Cho, Soo Min; Lee, Dong Goo; Cho, Kyul; Abd el-Aty, A M; Shim, Jae-Han; Lee, Soon-Ho; Jeong, Ji-Yoon; Shin, Ho-Chul

    2010-04-01

    In this study, a simplified method for the extraction and determination of seven fluoroquinolone residues (danofloxacin, difloxacin, enrofloxacin, marbofloxacin, orbifloxacin, ofloxacin, and sarafloxacin) and three quinolones (oxolinic acid, flumequine, and nalidixic acid), in porcine muscle, table eggs, and commercial whole milk, which required no cleanup step, was devised. This procedure involves the extraction of analytes from the samples via liquid-phase extraction, and the subsequent quantitative determination was accomplished via LC-fluorescence detection. Analyte separation was successfully conducted on an XBridge-C(18) column, with a linear gradient mobile phase composed of acetonitrile and 0.01 M oxalic acid buffer at pH=3.5. The one-step liquid-liquid extraction method evidenced good selectivity, precision (RSDs=0.26-15.07%), and recovery of the extractable analytes, ranging from 61.12 to 115.93% in matrices. The LOQs ranged from 0.3 to 25 microg/kg. A survey of ten samples purchased from local markets was conducted, and none of the samples harbored fluoroquinolone residues. This method is an improvement over existing methodologies, since no additional cleanup was necessary.

  5. Quantitation of fluoroquinolones in honey using tandem mass spectrometry (LC-MS/MS): nested validation with two mass spectrometers.

    PubMed

    Durden, David A; Fernandes, Gwen

    2010-01-01

    A number of drugs in the quinolone and fluoroquinolone families, approved for veterinary treatment of food animals by various countries, may be used to treat bee diseases and thereby contaminate honey. An LC-MS/MS method has been developed for the quantification of the quinolones: flumequine, nalidixic acid, oxolinic acid, and pipemidic acid; and the fluoroquinolones ciprofloxacin, danofloxacin, difloxacin, enrofloxacin, norfloxacin, ofloxacin, orbifloxacin, marbofloxacin, sarafloxacin, and sparfloxacin. A method-matched calibration curve is used with several internal standards, i.e., ciprofloxacin-d8, Iomefloxacin, and cinoxacin, to correct for the various types of honey matrices: white, light, medium, and dark colors. Enoxacin is added as an external recovery standard. The LOD values range from 0.05 microg/kg (ofloxacin) to 0.4 microg/kg (flumequine). The compounds are verified by LC-MS/MS retention times and ion ratios. Method uncertainty was determined using two separate analytical systems. The method has successfully measured the presence of norfloxacin in several samples of honey imported into Canada.

  6. Carbapenem-resistant Enterobacteriaceae and the correlation between carbapenem and fluoroquinolone usage and resistance in the US military health system.

    PubMed

    Lesho, Emil P; Clifford, Robert J; Chukwuma, Uzo; Kwak, Yoon I; Maneval, Mark; Neumann, Charlotte; Xie, Suji; Nielsen, Lindsey E; Julius, Michael D; McGann, Patrick; Waterman, Paige E

    2015-02-01

    Whether carbapenem or fluoroquinolone usage is correlated with carbapenem-resistant Enterobacteriaceae (CRE) has not been investigated at the level of an entire US nationwide managed health care system. We analyzed 75 million person-years of surveillance and 1,969,315 cultures from all 266 hospitals in the geographically dispersed US military health system. Incidences of CRE remained under 1 case per 100,000 person-years. Incidences of CRE increased relative to 2005 baseline levels in 3 of 7 subsequent years, then decreased in 2012 (P<0.05). Incident proportions of carbapenem resistance (CR) differed significantly among years, geographical regions, and bacterial species. Although use and resistance strongly correlated (R>0.80) for several "drug-bug" combinations, none were significant at the national or facility level. One exception was that inpatient consumption of fluoroquinolones was significantly correlated (P=0.0007) with CR in Escherichia coli when data from the major referral centers of the Southern and Northern regions were combined.

  7. In vitro investigations into the use of antimicrobials in combination to maintain efficacy of fluoroquinolones in poultry.

    PubMed

    Randall, Luke; Ridley, Anne; Lemma, Fabrizio; Hale, Carol; Davies, Rob

    2016-10-01

    The aim of this study was to determine if apramycin, colistin or lincomycin-spectinomycin, in combination with enrofloxacin, was able prevent the emergence of mutants with reduced susceptibility to fluoroquinolone antibiotics in vitro. MICs were determined for enrofloxacin alone and in combination for panels of Campylobacter (n=37), Escherichia coli (n=52) and Salmonella (n=52) isolates. MIC results suggested that apramycin, colistin and lincomycin-spectinomycin worked in an additive/indifferent way when each was combined with enrofloxacin. Apramycin was considered the most promising antibiotic for combination-therapy in conjunction with enrofloxacin, and further evaluations (MBCs, MPCs and time-kill-curves) were performed for this combination for selected isolates. Results suggest combination-therapy of enrofloxacin with apramycin increases the efficacy, as well as decreasing the emergence and survival of bacteria with mutational resistance to fluoroquinolone antibiotics. Such combination-therapy, minimising the development of mutational resistance, may have relevance for Campylobacter, E. coli and Salmonella infections in poultry. PMID:27663369

  8. Protection Afforded by Fluoroquinolones in Animal Models of Respiratory Infections with Bacillus anthracis, Yersinia pestis, and Francisella tularensis.

    PubMed

    Peterson, Johnny W; Moen, Scott T; Healy, Daniel; Pawlik, Jennifer E; Taormina, Joanna; Hardcastle, Jason; Thomas, John M; Lawrence, William S; Ponce, Cindy; Chatuev, Bagram M; Gnade, Bryan T; Foltz, Sheri M; Agar, Stacy L; Sha, Jian; Klimpel, Gary R; Kirtley, Michelle L; Eaves-Pyles, Tonyia; Chopra, Ashok K

    2010-01-01

    Successful treatment of inhalation anthrax, pneumonic plague and tularemia can be achieved with fluoroquinolone antibiotics, such as ciprofloxacin and levofloxacin, and initiation of treatment is most effective when administered as soon as possible following exposure. Bacillus anthracis Ames, Yersinia pestis CO92, and Francisella tularensis SCHU S4 have equivalent susceptibility in vitro to ciprofloxacin and levofloxacin (minimal inhibitory concentration is 0.03 μg/ml); however, limited information is available regarding in vivo susceptibility of these infectious agents to the fluoroquinolone antibiotics in small animal models. Mice, guinea pig, and rabbit models have been developed to evaluate the protective efficacy of antibiotic therapy against these life-threatening infections. Our results indicated that doses of ciprofloxacin and levofloxacin required to protect mice against inhalation anthrax were approximately 18-fold higher than the doses of levofloxacin required to protect against pneumonic plague and tularemia. Further, the critical period following aerosol exposure of mice to either B. anthracis spores or Y. pestis was 24 h, while mice challenged with F. tularensis could be effectively protected when treatment was delayed for as long as 72 h postchallenge. In addition, it was apparent that prolonged antibiotic treatment was important in the effective treatment of inhalation anthrax in mice, but short-term treatment of mice with pneumonic plague or tularemia infections were usually successful. These results provide effective antibiotic dosages in mice, guinea pigs, and rabbits and lay the foundation for the development and evaluation of combinational treatment modalities. PMID:21127743

  9. Protection Afforded by Fluoroquinolones in Animal Models of Respiratory Infections with Bacillus anthracis, Yersinia pestis, and Francisella tularensis

    PubMed Central

    Peterson, Johnny W; Moen, Scott T; Healy, Daniel; Pawlik, Jennifer E; Taormina, Joanna; Hardcastle, Jason; Thomas, John M; Lawrence, William S; Ponce, Cindy; Chatuev, Bagram M; Gnade, Bryan T; Foltz, Sheri M; Agar, Stacy L; Sha, Jian; Klimpel, Gary R; Kirtley, Michelle L; Eaves-Pyles, Tonyia; Chopra, Ashok K

    2010-01-01

    Successful treatment of inhalation anthrax, pneumonic plague and tularemia can be achieved with fluoroquinolone antibiotics, such as ciprofloxacin and levofloxacin, and initiation of treatment is most effective when administered as soon as possible following exposure. Bacillus anthracis Ames, Yersinia pestis CO92, and Francisella tularensis SCHU S4 have equivalent susceptibility in vitro to ciprofloxacin and levofloxacin (minimal inhibitory concentration is 0.03 μg/ml); however, limited information is available regarding in vivo susceptibility of these infectious agents to the fluoroquinolone antibiotics in small animal models. Mice, guinea pig, and rabbit models have been developed to evaluate the protective efficacy of antibiotic therapy against these life-threatening infections. Our results indicated that doses of ciprofloxacin and levofloxacin required to protect mice against inhalation anthrax were approximately 18-fold higher than the doses of levofloxacin required to protect against pneumonic plague and tularemia. Further, the critical period following aerosol exposure of mice to either B. anthracis spores or Y. pestis was 24 h, while mice challenged with F. tularensis could be effectively protected when treatment was delayed for as long as 72 h postchallenge. In addition, it was apparent that prolonged antibiotic treatment was important in the effective treatment of inhalation anthrax in mice, but short-term treatment of mice with pneumonic plague or tularemia infections were usually successful. These results provide effective antibiotic dosages in mice, guinea pigs, and rabbits and lay the foundation for the development and evaluation of combinational treatment modalities. PMID:21127743

  10. High performance liquid chromatography coupled with resonance Rayleigh scattering for the detection of three fluoroquinolones and mechanism study.

    PubMed

    Zhou, Mingqiong; Peng, Jingdong; He, Rongxing; He, Yuting; Zhang, Jing; Li, Aiping

    2015-02-01

    A reliable and versatile high performance liquid chromatography coupled with resonance Rayleigh scattering method was established for the determination of three fluoroquinolones, including levofloxacin, norfloxacin and enrofloxacin in water sample and human urine sample. In pH 4.4-4.6 Britton-Robinson buffer medium, the fluoroquinolones separated by high performance liquid chromatography could react with erythrosine to form 1:1 ion-association complexes, which could make contributions to the great enhancement of RRS. The resonance Rayleigh scattering signal was recorded at λex=λem=330 nm. The resonance Rayleigh scattering spectral characteristics of the drugs and the experimental conditions such as pH, detection wavelength, erythrosine concentration, flow rate, the length of reaction tube were studied. Quantum chemistry calculation, Fourier transform infrared spectroscopy and absorption spectroscopy were used to discuss the reaction mechanism. The recoveries of samples added standard ranged from 97.53% to 102.00%, and the relative standard deviation was below 4.64%. The limit of detection (S/N=3) of 0.05-0.12 μg mL(-1) was reached, and the linear regression coefficients were all above 0.999. The proposed method was proved as a simple, low cost and high sensitivity method.

  11. New Real-Time PCR Assay Using Locked Nucleic Acid Probes To Assess Prevalence of ParC Mutations in Fluoroquinolone-Susceptible Streptococcus pneumoniae Isolates from France

    PubMed Central

    Decousser, Jean-Winoc; Methlouthi, Imen; Pina, Patrick; Collignon, Anne; Allouch, Pierre

    2006-01-01

    A real-time PCR assay with locked nucleic acid probes was developed to screen mutations at codons 79 and 83 of the Streptococcus pneumoniae parC gene. Only silent mutations were detected among 236 French invasive fluoroquinolone-susceptible strains. This test could be useful for some high-risk patients or in national surveys. PMID:16569894

  12. Molecular Typing of Fluoroquinolone-Resistant Campylobacter jejuni Isolated from Broilers in Japan Using Multilocus Sequence Typing and Pulsed-Field Gel Electrophoresis.

    PubMed

    Ozawa, Manao; Hiki, Mototaka; Kawanishi, Michiko; Abo, Hitoshi; Kojima, Akemi; Asai, Tetsuo; Hamamoto, Shuichi

    2016-01-01

    Fluoroquinolone-resistant Campylobacter jejuni isolates from broilers in Japan were characterized using multilocus sequence typing and pulsed-field gel electrophoresis (PFGE) in order to elucidate the genetic relationship between these strains. Forty-three of the isolates were classified into 20 sequence types and were clustered into 21 PFGE types with 70% similarity. The most dominant clonal complex (CC) was CC-21 (41.9%). Diverse PFGE patterns were observed within the same CC, but the combined analysis of PFGE type and CC revealed that the strains with the same combination were isolated from the same district or neighboring districts. On the other hand, strains with the same combination pattern were also isolated from geographically distant districts. Our results elucidate two possible reasons for the prevalence of fluoroquinolone-resistant C. jejuni among broiler farms: (1) the resistant C. jejuni is clonally disseminated within the limited area, and (2) susceptible C. jejuni acquired fluoroquinolone resistance during the use of fluoroquinolone on the farms.

  13. Unexpected distribution of the fluoroquinolone-resistance gene qnrB in Escherichia coli isolates from different human and poultry origins in Ecuador.

    PubMed

    Armas-Freire, Paulina I; Trueba, Gabriel; Proaño-Bolaños, Carolina; Levy, Karen; Zhang, Lixin; Marrs, Carl F; Cevallos, William; Eisenberg, Joseph N S

    2015-06-01

    Fluoroquinolone resistance can be conferred through chromosomal mutations or by the acquisition of plasmids carrying genes such as the quinolone resistance gene (qnr). In this study, 3,309 strains of commensal Escherichia coli were isolated in Ecuador from: (i) humans and chickens in a rural northern coastal area (n = 2368, 71.5%) and (ii) chickens from an industrial poultry operation (n = 827, 25%). In addition, 114 fluoroquinolone-resistant strains from patients with urinary tract infections who were treated at three urban hospitals in Quito, Ecuador were analyzed. All of the isolates were subjected to antibiotic susceptibility screening. Fluoroquinolone-resistant isolates (FRIs) were then screened for the presence of qnrB genes. A significantly higher phenotypic resistance to fluoroquinolones was determined in E. coli strains from chickens in both the rural area (22%) and the industrial operation (10%) than in strains isolated from humans in the rural communities (3%). However, the rates of qnrB genes in E. coli isolates from healthy humans in the rural communities (11 of 35 isolates, 31%) was higher than in chickens from either the industrial operations (3 of 81 isolates, 6%) or the rural communities (7 of 251 isolates, 2.8%). The occurrence of qnrB genes in human FRIs obtained from urban hospitals was low (1 of 114 isolates, 0.9%). These results suggested that the qnrB gene is more widely distributed in rural settings, where antibiotic usage is low, than in urban hospitals and industrial poultry operations. The role of qnrB in clinical resistance to fluoroquinolones is thus far unknown.

  14. Comparative Outcome Analysis of Penicillin-Based Versus Fluoroquinolone-Based Antibiotic Therapy for Community-Acquired Pneumonia: A Nationwide Population-Based Cohort Study.

    PubMed

    Wang, Chi-Chuan; Lin, Chia-Hui; Lin, Kuan-Yin; Chuang, Yu-Chung; Sheng, Wang-Huei

    2016-02-01

    Community-acquired pneumonia (CAP) is a common but potentially life-threatening condition, but limited information exists on the effectiveness of fluoroquinolones compared to β-lactams in outpatient settings. We aimed to compare the effectiveness and outcomes of penicillins versus respiratory fluoroquinolones for CAP at outpatient clinics.This was a claim-based retrospective cohort study. Patients aged 20 years or older with at least 1 new pneumonia treatment episode were included, and the index penicillin or respiratory fluoroquinolone therapies for a pneumonia episode were at least 5 days in duration. The 2 groups were matched by propensity scores. Cox proportional hazard models were used to compare the rates of hospitalizations/emergence service visits and 30-day mortality. A logistic model was used to compare the likelihood of treatment failure between the 2 groups.After propensity score matching, 2622 matched pairs were included in the final model. The likelihood of treatment failure of fluoroquinolone-based therapy was lower than that of penicillin-based therapy (adjusted odds ratio [AOR], 0.88; 95% confidence interval [95%CI], 0.77-0.99), but no differences were found in hospitalization/emergence service (ES) visits (adjusted hazard ratio [HR], 1.27; 95% CI, 0.92-1.74) and 30-day mortality (adjusted HR, 0.69; 95% CI, 0.30-1.62) between the 2 groups.The likelihood of treatment failure of fluoroquinolone-based therapy was lower than that of penicillin-based therapy for CAP on an outpatient clinic basis. However, this effect may be marginal. Further investigation into the comparative effectiveness of these 2 treatment options is warranted.

  15. Overexpression of the Novel MATE Fluoroquinolone Efflux Pump FepA in Listeria monocytogenes Is Driven by Inactivation of Its Local Repressor FepR

    PubMed Central

    Guérin, François; Galimand, Marc; Tuambilangana, Fabrice; Courvalin, Patrice; Cattoir, Vincent

    2014-01-01

    Whereas fluoroquinolone resistance mainly results from target modifications in gram-positive bacteria, it is primarily due to active efflux in Listeria monocytogenes. The aim of this study was to dissect a novel molecular mechanism of fluoroquinolone resistance in this important human pathogen. Isogenic L. monocytogenes clinical isolates BM4715 and BM4716, respectively susceptible and resistant to fluoroquinolones, were studied. MICs of norfloxacin and ciprofloxacin were determined in the presence or in the absence of reserpine (10 mg/L). Strain BM4715 was susceptible to norfloxacin (MIC, 4 mg/L) and ciprofloxacin (MIC, 0.5 mg/L) whereas BM4716 was highly resistant to both drugs (MICs 128 and 32 mg/L, respectively). Reserpine was responsible for a 16-fold decrease in both norfloxacin and ciprofloxacin MICs against BM4716 suggesting efflux associated resistance. Whole-genome sequencing of the strains followed by comparative genomic analysis revealed a single point mutation in the gene for a transcriptional regulator, designated fepR (for fluoroquinolone efflux protein regulator) belonging to the TetR family. The frame-shift mutation was responsible for the introduction of a premature stop codon resulting in an inactive truncated protein. Just downstream from fepR, the structural gene for an efflux pump of the MATE family (named FepA) was identified. Gene expression was quantified by qRT-PCR and demonstrated that fepA expression was more than 64-fold higher in BM4716 than in BM4715. The clean deletion of the fepR gene from BM4715 was responsible for an overexpression of fepA with resistance to norfloxacin and ciprofloxacin, confirming the role of FepR as a local repressor of fepA. In conclusion, we demonstrated that overexpression of the new MATE efflux pump FepA is responsible for fluoroquinolone resistance in L. monocytogenes and secondary to inactivation of the FepR repressor. PMID:25188450

  16. Molecular epidemiology and genetic diversity of fluoroquinolone-resistant Escherichia coli isolates from patients with community-onset infections in 30 Chinese county hospitals.

    PubMed

    Zhao, Lina; Zhang, Jing; Zheng, Beiwen; Wei, Zeqing; Shen, Ping; Li, Sujuan; Li, Lanjuan; Xiao, Yonghong

    2015-03-01

    The high frequency of fluoroquinolone resistance in Escherichia coli is a feature of clinical bacteriology in China, where the molecular epidemiology and genetic characteristics of this resistance in county hospitals remain unclear. A total of 590 nonduplicate E. coli isolates from 30 county hospitals located across seven Chinese regions were examined for plasmid-mediated quinolone resistance (PMQR) genes and mutations in quinolone resistance-determining regions (QRDRs). Multilocus sequence typing (MLST) and phylogenetic analysis of fluoroquinolone-resistant isolates were used to determine their genetic relatedness. The ciprofloxacin resistance rate of community-onset E. coli was 51.2%, and at least one PMQR gene was carried by 220 (37.3%) isolates. These included qnr (3.7%), aac(6')-Ib-cr (19.7%), qepA (14.4%), and oqxAB (3.8%). Two novel oqxB mutants were identified and named oqxB20 and oqxB29. From 60 sequence types (STs) isolated, 5 novel STs (ST4499 to ST4503) were identified. ST1193 (7.9%) was the second most abundant ST among fluoroquinolone-resistant isolates (ST131 was the most common, with 14.6%), and this is the first report of it in China. This is also the first report of ST2115 and ST3014 isolates from human samples. Ciprofloxacin-resistant E. coli isolates fell mainly into phylogroups B2 and D. The rates of fluoroquinolone resistance and the prevalence of PMQR genes in community-onset E. coli isolates from Chinese county hospitals were high. The wide-ranging molecular epidemiology of E. coli isolates from scattered locations across China indicates that fluoroquinolone resistance evolved from different sources.

  17. Determination of fluoroquinolone antibiotics via ionic-liquid-based, salt-induced, dual microextraction in swine feed.

    PubMed

    Wang, Huili; Gao, Ming; Gao, Jiajia; Yu, Nana; Huang, Hong; Yu, Qing; Wang, Xuedong

    2016-09-01

    In conventional microextraction procedures, the disperser (organic solvent or ionic liquid) is left in the aqueous phase and discarded after finishing the microextraction process. Because the disperser is water-soluble, it results in low extraction recovery for polar compounds. In this investigation, an ionic-liquid-based microextraction (ILBME) was integrated with salting-out assisted liquid-liquid microextraction (SALLME) to build an ionic-liquid-based, salt-induced, dual microextraction (ILSDME) for isolation of five fluoroquinolone antibiotics (FQs) with high polarity (log P, -1.0 to 1.0). The proposed ILSDME method incorporates a dual microextraction by converting the disperser in the ILBME to the extractor in the SALLME. Optimization of key factors was conducted by integrating single-factor experiments and central composite design. The optimized experimental parameters were 80 μL [C8MIM][PF6] as extractor, 505 μL acetone as disperser, pH = 2.0, 4.1 min extraction time, and 4.2 g of Na2SO4. Under optimized conditions, high ERs (90.6-103.2 %) and low LODs (0.07-0.61 μg kg(-1)) were determined for five FQs in swine feed. Experimental precision based on RSDs was 1.4-5.2 % for intra-day and 2.4-6.9 % for inter-day analyses. The combination of ILBME with SALLME increased FQ recoveries by 15-20 % as compared with SALLME, demonstrating that the ILSDME method can enhance extraction efficiency for polar compounds compared to single-step microextraction. Therefore, the ILSDME method developed in this study has wide application for pretreatment of moderately to highly polar pollutants in complex matrices. Graphical Abstract A dual microextraction was developed by integrating ionic-liquid-based microextraction with salting-out assisted liquid-liquid microextraction for isolation of five fluoroquinolone antibiotics (FQs) with high polarity (log P = -1.0 to 1.0). The principle of dual microextraction is based on converting the remaining disperser from

  18. Computer-Generated Geometry Instruction: A Preliminary Study

    ERIC Educational Resources Information Center

    Kang, Helen W.; Zentall, Sydney S.

    2011-01-01

    This study hypothesized that increased intensity of graphic information, presented in computer-generated instruction, could be differentially beneficial for students with hyperactivity and inattention by improving their ability to sustain attention and hold information in-mind. To this purpose, 18 2nd-4th grade students, recruited from general…

  19. Preparation of a monolith functionalized with zinc oxide nanoparticles and its application in the enrichment of fluoroquinolone antibiotics.

    PubMed

    Liu, Dan; Ma, Jiutong; Jin, Yan; Li, Xiqian; Zhou, Xiao; Jia, Qiong; Zhou, Weihong

    2015-01-01

    This study describes the enrichment ability of ZnO-modified methacrylic acid-co-ethylene dimethacrylate polymer monoliths as stationary phases for the simultaneous determination of antibiotics (ofloxacin, ciprofloxacin, enoxacin, and pefloxacin) combined with high-performance liquid chromatography. The prepared monolith was characterized by scanning electron microscopy, X-ray photoelectron spectroscopy, Fourier-transformed infrared spectroscopy, and thermogravimetric analysis. The polymer monolith microextraction method has been applied to the enrichment of fluoroquinolone antibiotics and satisfactory results were obtained in the analysis of water samples. Compared with the conventional methacrylic acid based monolith, the developed monolith exhibited a higher enrichment capacity because of the introduction of zinc oxide into the preparation process.

  20. Pharmacokinetic Drug Interactions of Antimicrobial Drugs: A Systematic Review on Oxazolidinones, Rifamycines, Macrolides, Fluoroquinolones, and Beta-Lactams

    PubMed Central

    Bolhuis, Mathieu S.; Panday, Prashant N.; Pranger, Arianna D.; Kosterink, Jos G. W.; Alffenaar, Jan-Willem C.

    2011-01-01

    Like any other drug, antimicrobial drugs are prone to pharmacokinetic drug interactions. These drug interactions are a major concern in clinical practice as they may have an effect on efficacy and toxicity. This article provides an overview of all published pharmacokinetic studies on drug interactions of the commonly prescribed antimicrobial drugs oxazolidinones, rifamycines, macrolides, fluoroquinolones, and beta-lactams, focusing on systematic research. We describe drug-food and drug-drug interaction studies in humans, affecting antimicrobial drugs as well as concomitantly administered drugs. Since knowledge about mechanisms is of paramount importance for adequate management of drug interactions, the most plausible underlying mechanism of the drug interaction is provided when available. This overview can be used in daily practice to support the management of pharmacokinetic drug interactions of antimicrobial drugs. PMID:24309312

  1. Four generations, Higgs physics, and the MSSM

    SciTech Connect

    Dawson, S.; Jaiswal, P.

    2010-10-01

    We consider the effects of a fourth generation of chiral fermions within the MSSM (minimal supersymmetric standard model). Such a model offers the possibility of having the lightest neutral Higgs boson significantly heavier than in the three generation MSSM. The model is highly constrained by precision electroweak data, along with Higgs searches at the Tevatron. In addition, the requirements of perturbative unitarity and direct searches for heavy quarks imply that the four generation MSSM is only consistent for tan{beta}{approx}1 and highly tuned 4th generation fermion masses.

  2. Molecular Analysis of Rising Fluoroquinolone Resistance in Belgian Non-Invasive Streptococcus pneumoniae Isolates (1995-2014).

    PubMed

    Ceyssens, Pieter-Jan; Van Bambeke, Françoise; Mattheus, Wesley; Bertrand, Sophie; Fux, Frédéric; Van Bossuyt, Eddie; Damée, Sabrina; Nyssen, Henry-Jean; De Craeye, Stéphane; Verhaegen, Jan; Tulkens, Paul M; Vanhoof, Raymond

    2016-01-01

    We present the results of a longitudinal surveillance study (1995-2014) on fluoroquinolone resistance (FQ-R) among Belgian non-invasive Streptococcus pneumoniae isolates (n = 5,602). For many years, the switch to respiratory fluoroquinolones for the treatment of (a)typical pneumonia had no impact on FQ-R levels. However, since 2011 we observed a significant decrease in susceptibility towards ciprofloxacin, ofloxacin and levofloxacin with peaks of 9.0%, 6.6% and 3.1% resistant isolates, respectively. Resistance to moxifloxacin arised sporadically, and remained <1% throughout the entire study period. We observed classical topoisomerase mutations in gyrA (n = 25), parC (n = 46) and parE (n = 3) in varying combinations, arguing against clonal expansion of FQ-R. The impact of recombination with co-habiting commensal streptococci on FQ-R remains marginal (10.4%). Notably, we observed that a rare combination of DNA Gyrase mutations (GyrA_S81L/GyrB_P454S) suffices for high-level moxifloxacin resistance, contrasting current model. Interestingly, 85/422 pneumococcal strains display MICCIP values which were lowered by at least four dilutions by reserpine, pointing at involvement of efflux pumps in FQ-R. In contrast to susceptible strains, isolates resistant to ciprofloxacin significantly overexpressed the ABC pump PatAB in comparison to reference strain S. pneumoniae ATCC 49619, but this could only be linked to disruptive terminator mutations in a fraction of these. Conversely, no difference in expression of the Major Facilitator PmrA, unaffected by reserpine, was noted between susceptible and resistant S. pneumoniae strains. Finally, we observed that four isolates displayed intermediate to high-level ciprofloxacin resistance without any known molecular resistance mechanism. Focusing future molecular studies on these isolates, which are also commonly found in other studies, might greatly assist in the battle against rising pneumococcal drug resistance. PMID:27227336

  3. In vitro susceptibilities to fluoroquinolones in current and archived Mycoplasma gallisepticum and Mycoplasma synoviae isolates from meat-type turkeys.

    PubMed

    Gerchman, Irina; Lysnyansky, Inna; Perk, Shimon; Levisohn, Sharon

    2008-10-15

    Monitoring of susceptibility to antibiotics in field isolates of pathogenic avian mycoplasmas is important for appropriate choice of treatment. Our study compared in vitro susceptibility to enrofloxacin and difloxacin in recent (2005-2006) isolates of Mycoplasma gallisepticum and Mycoplasma synoviae from meat-type turkey flocks with archived (1997-2003) isolates and reference strains. Comparison of minimal inhibitory concentration (MIC) values determined by microtest, agar dilution and commercial Etest showed good agreement, but underscored the need for standardized methods for testing. Notably, while the commercial Etest was convenient and accurate for determining MICs for enrofloxacin in the range 0.002-0.094microg/ml, the endpoint of inhibition for M. gallisepticum and M. synoviae strains with MIC values > or =1.0microg/ml could not be determined. A decrease in susceptibility to both fluoroquinolones was detected in archived strains but to a greater degree in recent isolates, most of which had MICs above the NCCLS susceptibility breakpoint for these antibiotics (< or =0.5microg/ml). In contrast, except for one flock, M. synoviae isolates were susceptible, although intrinsically less susceptible than M. gallisepticum. Overall for the 88 strains tested (45 M. gallisepticum, 43 M. synoviae), the MIC50 for both enrofloxacin and difloxacin was 0.5microg/ml. The isolation of fluoroquinolone-resistant M. gallisepticum isolates from breeder and broiler flocks as well as from meat-type turkeys suggests that these strains have become established in Israel, necessitating a reevaluation of antibiotic therapy. Periodic survey of MICs in field isolates of avian mycoplasmas to monitor for the possible appearance of resistant strains is recommended.

  4. Susceptibility of canine and feline bacterial pathogens to pradofloxacin and comparison with other fluoroquinolones approved for companion animals.

    PubMed

    Schink, Anne-Kathrin; Kadlec, Kristina; Hauschild, Tomasz; Brenner Michael, Geovana; Dörner, Julia C; Ludwig, Carolin; Werckenthin, Christiane; Hehnen, Hans-Robert; Stephan, Bernd; Schwarz, Stefan

    2013-02-22

    In this study, 908 bacterial pathogens from defined infections of dogs and cats were tested for their susceptibility to the novel fluoroquinolone pradofloxacin, which was approved in 2011 for use in cats and dogs. Most of the bacteria tested (Staphylococcus aureus, Staphylococcus pseudintermedius, Escherichia coli, β-haemolytic streptococci, Pasteurella multocida and Bordetella bronchiseptica) exhibited low pradofloxacin MIC(90) values of ≤ 0.25 μg/ml. Solely Proteus spp. and Pseudomonas aeruginosa had higher MIC(90) values of ≥ 4 μg/ml. Only six (3.4%) of 177 S. pseudintermedius and 12 (5.3%) of 227 E. coli isolates showed pradofloxacin MICs of ≥ 2 μg/ml. Analysis of the quinolone resistance determining regions of the target genes identified double mutations in GyrA that resulted in amino acid exchanges S83L+D87N or S83L+D87Y and single or double mutations in ParC that resulted in amino acid exchanges S80I or S80I+E84G in all 12 E. coli isolates. The six S. pseudintermedius isolates exhibited amino acid exchanges S84L or E88K in GyrA and S80I in GrlA. Comparative analysis of the MICs of pradofloxacin and the MICs determined for enrofloxacin and its main metabolite ciprofloxacin, but also marbofloxacin, orbifloxacin, difloxacin and ibafloxacin was conducted for the target pathogens S. pseudintermedius, E. coli and P. multocida. This comparison confirmed that pradofloxacin MICs were significantly lower than those of the other tested fluoroquinolones.

  5. Molecular Analysis of Rising Fluoroquinolone Resistance in Belgian Non-Invasive Streptococcus pneumoniae Isolates (1995-2014)

    PubMed Central

    Ceyssens, Pieter-Jan; Van Bambeke, Françoise; Mattheus, Wesley; Bertrand, Sophie; Fux, Frédéric; Van Bossuyt, Eddie; Damée, Sabrina; Nyssen, Henry-Jean; De Craeye, Stéphane; Verhaegen, Jan; Tulkens, Paul M.; Vanhoof, Raymond

    2016-01-01

    We present the results of a longitudinal surveillance study (1995–2014) on fluoroquinolone resistance (FQ-R) among Belgian non-invasive Streptococcus pneumoniae isolates (n = 5,602). For many years, the switch to respiratory fluoroquinolones for the treatment of (a)typical pneumonia had no impact on FQ-R levels. However, since 2011 we observed a significant decrease in susceptibility towards ciprofloxacin, ofloxacin and levofloxacin with peaks of 9.0%, 6.6% and 3.1% resistant isolates, respectively. Resistance to moxifloxacin arised sporadically, and remained <1% throughout the entire study period. We observed classical topoisomerase mutations in gyrA (n = 25), parC (n = 46) and parE (n = 3) in varying combinations, arguing against clonal expansion of FQ-R. The impact of recombination with co-habiting commensal streptococci on FQ-R remains marginal (10.4%). Notably, we observed that a rare combination of DNA Gyrase mutations (GyrA_S81L/GyrB_P454S) suffices for high-level moxifloxacin resistance, contrasting current model. Interestingly, 85/422 pneumococcal strains display MICCIP values which were lowered by at least four dilutions by reserpine, pointing at involvement of efflux pumps in FQ-R. In contrast to susceptible strains, isolates resistant to ciprofloxacin significantly overexpressed the ABC pump PatAB in comparison to reference strain S. pneumoniae ATCC 49619, but this could only be linked to disruptive terminator mutations in a fraction of these. Conversely, no difference in expression of the Major Facilitator PmrA, unaffected by reserpine, was noted between susceptible and resistant S. pneumoniae strains. Finally, we observed that four isolates displayed intermediate to high-level ciprofloxacin resistance without any known molecular resistance mechanism. Focusing future molecular studies on these isolates, which are also commonly found in other studies, might greatly assist in the battle against rising pneumococcal drug resistance. PMID:27227336

  6. Nuclear Science Symposium, 4th, and Nuclear Power Systems Symposium, 9th, San Francisco, Calif., October 19-21, 1977, Proceedings

    NASA Technical Reports Server (NTRS)

    1978-01-01

    Consideration is given to the following types of high energy physics instrumentation: drift chambers, multiwire proportional chambers, calorimeters, optical detectors, ionization and scintillation detectors, solid state detectors, and electronic and digital subsystems. Attention is also paid to reactor instrumentation, nuclear medicine instrumentation, data acquisition systems for nuclear instrumentation, microprocessor applications in nuclear science, environmental instrumentation, control and instrumentation of nuclear power generating stations, and radiation monitoring. Papers are also presented on instrumentation for the High Energy Astronomy Observatory.

  7. Feasibility Study of Supercritical Light Water Cooled Fast Reactors for Actinide Burning and Electric Power Production, Progress Report for Work Through September 2002, 4th Quarterly Report

    SciTech Connect

    Mac Donald, Philip Elsworth

    2002-09-01

    The use of light water at supercritical pressures as the coolant in a nuclear reactor offers the potential for considerable plant simplification and consequent capital and O&M cost reduction compared with current light water reactor (LWR) designs. Also, given the thermodynamic conditions of the coolant at the core outlet (i.e. temperature and pressure beyond the water critical point), very high thermal efficiencies of the power conversion cycle are possible (i.e. up to about 45%). Because no change of phase occurs in the core, the need for steam separators and dryers as well as for BWR-type re-circulation pumps is eliminated, which, for a given reactor power, results in a substantially shorter reactor vessel and smaller containment building than the current BWRs. Furthermore, in a direct cycle the steam generators are not needed. If no additional moderator is added to the fuel rod lattice, it is possible to attain fast neutron energy spectrum conditions in a supercritical water-cooled reactor (SCWR). This type of core can make use of either fertile or fertile-free fuel and retain a hard spectrum to effectively burn plutonium and minor actinides from LWR spent fuel while efficiently generating electricity. One can also add moderation and design a thermal spectrum SCWR. The Generation IV Roadmap effort has identified the thermal spectrum SCWR (followed by the fast spectrum SCWR) as one of the advanced concepts that should be developed for future use. Therefore, the work in this NERI project is addressing both types of SCWRs.

  8. [Simultaneous determination of residues of three fluoroquinolones in chicken using high performance liquid chromatography with post-column derivatization and terbium sensitized fluorescence].

    PubMed

    Qi, Kezong; Zhu, Liangqiang; Sun, Guoren; Shi, Zuhao; Peng, Kaisong

    2007-07-01

    A method of high performance liquid chromatography with post-column derivatization and terbium sensitized fluorescence for simultaneous determination of residues of ciprofloxacin, norfloxacin and enrofloxacin in chicken was established, based on the effect that Tb3+ can sensibilize fluorescence of fluoroquinolones. Under the optimal chromatographic condition, three fluoroquinolones were separated on a C18 column with 0.05 mol/L acetic acid/acetate buffer-acetonitrile (89:11, v/v) as the mobile phase, and at a flow rate of 0.8 mL/min; then were derivatized with 8 x 10(-5) mol/L Tb3+ at 40 degrees C, and at a flow rate of 0.5 mL/min; finally were detected using a fluorescence detector (lamda(ex) = 271 nm, lamda(em) = 545 nm). The recoveries of three fluoroquinolones ranged from 66.3%-88.0% at the added levels of 1.0, 10.0, 50.0, and 100.0 ng/g, and the relative standard deviations (RSDs) were less than 15.0%. The linear range for quantitative analysis was between 0.1 and 500 ng/mL. All the RSDs of the inter-day and intra-day analyses were less than 13.0%. The detection limits were 0.05 ng/g for ciprofloxacin and norfloxacin and 0.08 ng/g for enrofloxacin. The method is sensitive for the determination of multi-residues of fluoroquinolones in chicken.

  9. Development and Evaluation of a Novel Single-Nucleotide-Polymorphism Real-Time PCR Assay for Rapid Detection of Fluoroquinolone-Resistant Mycoplasma bovis▿ †

    PubMed Central

    Ben Shabat, M.; Mikula, I.; Gerchman, I.; Lysnyansky, I.

    2010-01-01

    Monitoring of the susceptibility of Mycoplasma bovis field isolates to antibiotics is important for the appropriate choice of treatment. However, in vitro susceptibility testing of mycoplasmas is technically demanding and time-consuming, especially for clinical isolates, and is rarely performed in mycoplasma diagnostic laboratories. Thus, the development of methods allowing rapid real-time detection of resistant strains of M. bovis in clinical samples is a high priority for successful treatment. In this study, a novel TaqMan single-nucleotide-polymorphism (SNP) real-time PCR assay, which enables the rapid identification of M. bovis strains with different susceptibilities to fluoroquinolones, was developed and evaluated. The TaqMan SNP real-time PCR assay is based on the amplification of a 97-bp fragment of the parC quinolone resistance-determining region (QRDR) and allows the specific detection of four possible genotypes: GAC or GAT (susceptible to fluoroquinolones) and AAC or AAT (resistant to fluoroquinolones). Four TaqMan minor groove binder (MGB) probes identifying 1-base mismatches were designed and applied in a dual-probe assay with two reaction tubes. The TaqMan SNP real-time PCRs developed are highly specific for M. bovis, with a detection limit of 5 fg/μl (about 5 M. bovis genomes). In addition, all four SNP real-time PCR tests have almost the same efficiency (97.7% [GAC], 94% [AAC], 99.99% [GAT], and 98% [AAT]). Taken together, the data suggest that this SNP real-time PCR assay has potential as a routine diagnostic test for the detection of decreased susceptibility of M. bovis to fluoroquinolones. PMID:20534803

  10. A novel and sensitive fluorescence immunoassay for the detection of fluoroquinolones in animal-derived foods using upconversion nanoparticles as labels.

    PubMed

    Hu, Gaoshuang; Sheng, Wei; Zhang, Yan; Wu, Xuening; Wang, Shuo

    2015-11-01

    A novel fluorescence immunoassay to detect fluoroquinolones in animal-derived foods was developed for the first time by use of upconversion nanoparticles as signal-probe labels. The bioassay system was established by the use of coating-antigen-modified polystyrene particles as immune-sensing probes for separation and anti-norfloxacin monoclonal antibody conjugated with carboxyl-functionalized NaYF4:Yb,Er upconversion nanoparticles which were prepared via a pyrolysis method and a subsequent ligand exchange process as fluorescent-signal probes (emission intensity recorded at 542 nm with excitation at 980 nm). Under optimized conditions, detection of fluoroquinolones was performed easily. The detection limit of this fluorescence immunoassay for norfloxacin, for example, was 10 pg mL(-1), within a wide linear range of 10 pg mL(-1) to 10 ng mL(-1) (R (2)  = 0.9959). For specificity analysis, the data obtained indicate this method could be applied in broad-spectrum detection of fluoroquinolones. The recoveries of norfloxacin-spiked animal-derived foods ranged from 82.37 to 132.22 %, with coefficients of variation of 0.24-25.06 %. The extraction procedure was rapid and simple, especially for milk samples, which could be analyzed directly without any pretreatment. In addition, the results obtained with the method were in good agreement with those obtained with commercial ELISA kits. The fluorescence immunoassay was more sensitive, especially with regard to the detection limit in milk samples (0.01 ng mL(-1) for norfloxacin): it was 50-fold more sensitive than commercial ELISA kits (0.5 ng mL(-1) for norfloxacin). The results show the proposed fluorescence immunoassay was facile, sensitive, and interference free, and is an alternative method for the quantitative detection of fluoroquinolone residues in animal-derived foods.

  11. Fourth Generation Parity

    SciTech Connect

    Lee, Hye-Sung; Soni, Amarjit

    2013-01-01

    We present a very simple 4th-generation (4G) model with an Abelian gauge interaction under which only the 4G fermions have nonzero charge. The U(1) gauge symmetry can have a Z_2 residual discrete symmetry (4G-parity), which can stabilize the lightest 4G particle (L4P). When the 4G neutrino is the L4P, it would be a neutral and stable particle and the other 4G fermions would decay into the L4P leaving the trace of missing energy plus the standard model fermions. Because of the new symmetry, the 4G particle creation and decay modes are different from those of the sequential 4G model, and the 4G particles can be appreciably lighter than typical experimental bounds.

  12. Optimization of a phase separation based magnetic-stirring salt-induced liquid-liquid microextraction method for determination of fluoroquinolones in food.

    PubMed

    Gao, Ming; Wang, Huili; Ma, Meiping; Zhang, Yuna; Yin, Xiaohan; Dahlgren, Randy A; Du, Dongli; Wang, Xuedong

    2015-05-15

    Herein, we developed a novel integrated apparatus to perform phase separation based on magnetic-stirring, salt-induced, liquid-liquid microextraction for determination of five fluoroquinolones in animal-based foods by HPLC analysis. The novel integrated apparatus consisted of three simple HDPE (high density polyethylene) parts that were used to separate the solvent from the aqueous solution prior to retrieving the extractant. The extraction parameters were optimized using the response surface method based on central composite design: 791 μL of acetone solvent, 2.5 g of Na2SO4, pH 1.7, 3.0 min of stir time, and 5.5 min centrifugation. The limits of detection were 0.07-0.53 μg kg(-1) and recoveries were 91.6-105.0% for the five fluoroquinolones from milk, eggs and honey. This method is easily constructed from inexpensive materials, extraction efficiency is high, and the approach is compatible with HPLC analysis. Thus, it has excellent prospects for sample pre-treatment and analysis of fluoroquinolones in animal-based foods. PMID:25577068

  13. Determination of fluoroquinolones in environmental water and milk samples treated with stir cake sorptive extraction based on a boron-rich monolith.

    PubMed

    Mei, Meng; Huang, Xiaojia

    2016-05-01

    In this study, a new stir cake sorptive extraction using a boron-rich monolith as the adsorbent was prepared by the in situ copolymerization of vinylboronic anhydride pyridine complex and divinylbenzene. The effect of preparation parameters, including the ratio of vinylboronic anhydride pyridine complex and divinylbenzene, monomer mixture, and porogen solvent, on extraction performance was investigated thoroughly. The physicochemical properties of the adsorbent were characterized by infrared spectroscopy, scanning electron microscopy, and mercury intrusion porosimetry. Several conditions affecting the extraction efficiency were investigated in detail. Under the optimized conditions, a convenient and sensitive method for the determination of trace fluoroquinolones residues in water and milk samples was established by coupling stir cake sorptive extraction with high-performance liquid chromatography and diode array detection. The limits of detection for the target compounds were 0.10-0.26 and 0.11-0.22 μg/L for water and milk samples, respectively. In addition, the developed method showed good linearity, repeatability, and precision. Finally, the proposed method was successfully applied for the detection of trace fluoroquinolones residues in environmental water and milk samples. Satisfactory recoveries were obtained for the determination of fluoroquinolones in spiking samples that ranged from 68.8 to 120%, with relative standard deviations below 10% in all cases. PMID:26990593

  14. Fluoroquinolone-Resistant and Extended-Spectrum β-Lactamase–Producing Escherichia coli Infections in Patients with Pyelonephritis, United States1

    PubMed Central

    Takhar, Sukhjit S.; Krishnadasan, Anusha; Abrahamian, Fredrick M.; Mower, William R.; Moran, Gregory J.

    2016-01-01

    For 2013–2014, we prospectively identified US adults with flank pain, temperature >38.0°C, and a diagnosis of acute pyelonephritis, confirmed by culture. Cultures from 453 (86.9%) of 521 patients grew Escherichia coli. Among E. coli isolates from 272 patients with uncomplicated pyelonephritis and 181 with complicated pyelonephritis, prevalence of fluoroquinolone resistance across study sites was 6.3% (range by site 0.0%–23.1%) and 19.9% (0.0%–50.0%), respectively; prevalence of extended-spectrum β-lactamase (ESBL) production was 2.6% (0.0%–8.3%) and 12.2% (0.0%–17.2%), respectively. Ten (34.5%) of 29 patients with ESBL infection reported no exposure to antimicrobial drugs, healthcare, or travel. Of the 29 patients with ESBL infection and 53 with fluoroquinolone-resistant infection, 22 (75.9%) and 24 (45.3%), respectively, were initially treated with in vitro inactive antimicrobial drugs. Prevalence of fluoroquinolone resistance exceeds treatment guideline thresholds for alternative antimicrobial drug strategies, and community-acquired ESBL-producing E. coli infection has emerged in some US communities. PMID:27532362

  15. In-tube magnetic solid phase microextraction of some fluoroquinolones based on the use of sodium dodecyl sulfate coated Fe3O4 nanoparticles packed tube.

    PubMed

    Manbohi, Ahmad; Ahmadi, Seyyed Hamid

    2015-07-23

    In-tube magnetic solid phase microextraction (in-tube MSPME) of fluoroquinolones from water and urine samples based on the use of sodium dodecyl sulfate (SDS) coated Fe3O4 nanoparticles packed tube has been reported. After the preparation of Fe3O4 nanoparticles (NPs) by a batch synthesis, these NPs were introduced into a stainless steel tube by a syringe and then a strong magnet was placed around the tube, so that the Fe3O4 NPs were remained in the tube and the tube was used in the in-tube SPME-HPLC/UV for the analysis of fluoroquinolones in water and urine samples. Plackett-Burman design was employed for screening the variables significantly affecting the extraction efficiency. Then, the significant factors were more investigated by Box-Behnken design. Calibration curves were linear (R(2)>0.990) in the range of 0.1-1000μgL(-1) for ciprofloxacin (CIP) and 0.5-500μgL(-1) for enrofloxacin (ENR) and ofloxacin (OFL), respectively. LODs for all studied fluoroquinolones ranged from 0.01 to 0.05μgL(-1). The main advantages of this method were rapid and easy automation and analysis, short extraction time, high sensitivity, possibility of fully sorbent collection after analysis, wide linear range and no need to organic solvents in extraction. PMID:26231896

  16. Determination of fluoroquinolones in environmental water and milk samples treated with stir cake sorptive extraction based on a boron-rich monolith.

    PubMed

    Mei, Meng; Huang, Xiaojia

    2016-05-01

    In this study, a new stir cake sorptive extraction using a boron-rich monolith as the adsorbent was prepared by the in situ copolymerization of vinylboronic anhydride pyridine complex and divinylbenzene. The effect of preparation parameters, including the ratio of vinylboronic anhydride pyridine complex and divinylbenzene, monomer mixture, and porogen solvent, on extraction performance was investigated thoroughly. The physicochemical properties of the adsorbent were characterized by infrared spectroscopy, scanning electron microscopy, and mercury intrusion porosimetry. Several conditions affecting the extraction efficiency were investigated in detail. Under the optimized conditions, a convenient and sensitive method for the determination of trace fluoroquinolones residues in water and milk samples was established by coupling stir cake sorptive extraction with high-performance liquid chromatography and diode array detection. The limits of detection for the target compounds were 0.10-0.26 and 0.11-0.22 μg/L for water and milk samples, respectively. In addition, the developed method showed good linearity, repeatability, and precision. Finally, the proposed method was successfully applied for the detection of trace fluoroquinolones residues in environmental water and milk samples. Satisfactory recoveries were obtained for the determination of fluoroquinolones in spiking samples that ranged from 68.8 to 120%, with relative standard deviations below 10% in all cases.

  17. Alterations in the Quinolone Resistance-Determining Regions and Fluoroquinolone Resistance in Clinical Isolates and Laboratory-Derived Mutants of Mycoplasma bovis: Not All Genotypes May Be Equal

    PubMed Central

    Khalil, Dima; Becker, Claire A. M.

    2015-01-01

    Mycoplasma bovis is considered a major contributor to respiratory diseases in young cattle. Resistant M. bovis isolates have increasingly been reported worldwide due to extensive use of antimicrobials to treat bovine pneumonia. The frequency of isolates resistant to fluoroquinolones varies considerably from one country to another. The MICs of isolates collected in France have only increased from “very low” to “low.” The present study was conducted to investigate whether alterations in the quinolone resistance-determining regions (QRDRs) could account for this slight modification in susceptibility. No correlation between QRDR alterations and increased MICs was evidenced in clinical isolates. In addition, all clinical isolates were subtyped, and the tendencies of the different sequence types to develop resistance through mutations in QRDRs under selective pressure in vitro were examined. In vitro, 3 hot spots for mutations in QRDRs (position 83 in GyrA and positions 80 and 84 in ParC) were associated with a high level of resistance when cumulated. We showed that the point mutations in the QRDRs observed in vitro were different (in location and selection rapidity) between the different subtypes. Our in vitro observations were corroborated by the recent detection of a clinical isolate highly resistant to fluoroquinolones (MIC ≥ 16 μg/ml) and belonging to the subtype which easily accumulates QRDR alterations in vitro. The current increased prevalence of this subtype in clinical isolates highlights the urgent need to control fluoroquinolone usage in veterinary medicine. PMID:26637606

  18. Optimization of a phase separation based magnetic-stirring salt-induced liquid-liquid microextraction method for determination of fluoroquinolones in food.

    PubMed

    Gao, Ming; Wang, Huili; Ma, Meiping; Zhang, Yuna; Yin, Xiaohan; Dahlgren, Randy A; Du, Dongli; Wang, Xuedong

    2015-05-15

    Herein, we developed a novel integrated apparatus to perform phase separation based on magnetic-stirring, salt-induced, liquid-liquid microextraction for determination of five fluoroquinolones in animal-based foods by HPLC analysis. The novel integrated apparatus consisted of three simple HDPE (high density polyethylene) parts that were used to separate the solvent from the aqueous solution prior to retrieving the extractant. The extraction parameters were optimized using the response surface method based on central composite design: 791 μL of acetone solvent, 2.5 g of Na2SO4, pH 1.7, 3.0 min of stir time, and 5.5 min centrifugation. The limits of detection were 0.07-0.53 μg kg(-1) and recoveries were 91.6-105.0% for the five fluoroquinolones from milk, eggs and honey. This method is easily constructed from inexpensive materials, extraction efficiency is high, and the approach is compatible with HPLC analysis. Thus, it has excellent prospects for sample pre-treatment and analysis of fluoroquinolones in animal-based foods.

  19. In-tube magnetic solid phase microextraction of some fluoroquinolones based on the use of sodium dodecyl sulfate coated Fe3O4 nanoparticles packed tube.

    PubMed

    Manbohi, Ahmad; Ahmadi, Seyyed Hamid

    2015-07-23

    In-tube magnetic solid phase microextraction (in-tube MSPME) of fluoroquinolones from water and urine samples based on the use of sodium dodecyl sulfate (SDS) coated Fe3O4 nanoparticles packed tube has been reported. After the preparation of Fe3O4 nanoparticles (NPs) by a batch synthesis, these NPs were introduced into a stainless steel tube by a syringe and then a strong magnet was placed around the tube, so that the Fe3O4 NPs were remained in the tube and the tube was used in the in-tube SPME-HPLC/UV for the analysis of fluoroquinolones in water and urine samples. Plackett-Burman design was employed for screening the variables significantly affecting the extraction efficiency. Then, the significant factors were more investigated by Box-Behnken design. Calibration curves were linear (R(2)>0.990) in the range of 0.1-1000μgL(-1) for ciprofloxacin (CIP) and 0.5-500μgL(-1) for enrofloxacin (ENR) and ofloxacin (OFL), respectively. LODs for all studied fluoroquinolones ranged from 0.01 to 0.05μgL(-1). The main advantages of this method were rapid and easy automation and analysis, short extraction time, high sensitivity, possibility of fully sorbent collection after analysis, wide linear range and no need to organic solvents in extraction.

  20. Exploring the active site of the Streptococcus pneumoniae topoisomerase IV–DNA cleavage complex with novel 7,8-bridged fluoroquinolones

    PubMed Central

    Laponogov, Ivan; Pan, Xiao-Su; Veselkov, Dennis A.; Cirz, Ryan T.; Wagman, Allan; Moser, Heinz E.

    2016-01-01

    As part of a programme of synthesizing and investigating the biological properties of new fluoroquinolone antibacterials and their targeting of topoisomerase IV from Streptococcus pneumoniae, we have solved the X-ray structure of the complexes of two new 7,8-bridged fluoroquinolones (with restricted C7 group rotation favouring tight binding) in complex with the topoisomerase IV from S. pneumoniae and an 18-base-pair DNA binding site—the E-site—found by our DNA mapping studies to bind drug strongly in the presence of topoisomerase IV (Leo et al. 2005 J. Biol. Chem. 280, 14 252–14 263, doi:10.1074/jbc.M500156200). Although the degree of antibiotic resistance towards fluoroquinolones is much lower than that of β-lactams and a range of ribosome-bound antibiotics, there is a pressing need to increase the diversity of members of this successful clinically used class of drugs. The quinolone moiety of the new 7,8-bridged agents ACHN-245 and ACHN-454 binds similarly to that of clinafloxocin, levofloxacin, moxifloxacin and trovofloxacin but the cyclic scaffold offers the possibility of chemical modification to produce interactions with other topoisomerase residues at the active site. PMID:27655731

  1. Emergence of Reduced Susceptibility and Resistance to Fluoroquinolones in Escherichia coli in Taiwan and Contributions of Distinct Selective Pressures

    PubMed Central

    McDonald, L. Clifford; Chen, Feng-Jui; Lo, Hsiu-Jung; Yin, Hsiao-Chuan; Lu, Po-Liang; Huang, Cheng-Hua; Chen, Pei; Lauderdale, Tsai-Ling; Ho, Monto

    2001-01-01

    A survey of 1,203 Escherichia coli isolates from 44 hospitals in Taiwan revealed that 136 (11.3%) isolates were resistant to fluoroquinolones and that another 261 (21.7%) isolates had reduced susceptibility. Resistance was more common in isolates responsible for hospital-acquired (mostly in intensive care units) infections (17.5%) than in other adult inpatient (11.4%; P = 0.08) and outpatient isolates (11.9%; P > 0.1). Similarly, reduced susceptibility was more common in isolates responsible for hospital-acquired infections (30.9%) than in other adult inpatient (21.0%; P = 0.04) and outpatient (21.4%; P = 0.06) isolates. Isolates from pediatric patients were less likely to be resistant (1.3 versus 12.0%; P < 0.01) but were nearly as likely to have reduced susceptibility (17.7 versus 21.9%; P > 0.1) as nonpediatric isolates. There was an inverse relationship in the proportion of isolates that were resistant versus the proportion that had reduced susceptibility among isolates from individual hospitals (R = 0.031; P < 0.05). In an analysis of isolates from two hospitals, all 9 resistant strains possessed double point mutations in gyrA and all 19 strains with reduced susceptibility strains had single point mutations; no mutations were found among fully susceptible strains. Risk factors for resistance included underlying cancer (odds ratio [OR], 83; 95% confidence interval [CI95], 7.3 to 2,241; P < 0.001), exposure to a quinolone (OR, undefined; P = 0.02), and exposure to a nonquinolone antibiotic (OR, 20; CI95, 2.2 to 482; P < 0.001); underlying cancer was the only independent risk factor (OR, 83; CI95, 8.6 to 807; P < 0.001). There were no significant associations between any of these factors and reduced susceptibility. Whereas acute and chronic quinolone use in cancer patients is a major selective pressure for resistance, other undetermined but distinct selective pressures appear to be more responsible for reduced susceptibility to fluoroquinolones in E. coli. PMID

  2. Effects of carry-over of fluoroquinolones on the susceptibility of commensal Escherichia coli in the intestinal microbiota of poultry.

    PubMed

    Scherz, Gesine; Stahl, Jessica; Glünder, Gerhard; Kietzmann, Manfred

    2014-01-01

    Due to the frequent use of antibacterials in veterinary medicine as well as in human medicine the occurrence of antibacterial resistance rises worldwide. But independent of the usage of antimicrobials the microbiota from animals as well as from humans already harbour a diversity of resistance genes. As a consequence of manufacturing animal production the treatment of livestock in case of illness is carried out via feed or drinking water. This automatically implies several risks. It has been demonstrated that an antibiotic treatment of livestock via feed or drinking water cause an accumulation of antibiotics and their metabolites in the direct environment of animals. This can lead to a carry-over or rather a resumption of the antimicrobials and their metabolites. Thus, the aim of this study was to determine the influence of carry-over of enrofloxacin as a representative of the fluoroquinolones on the development of bacterial resistance of commensal E. coli in the intestinal microbiota of poultry. Therefore four different treatment groups were provided and the minimal inhibitory concentrations (MICs) of commensal E. coli were measured: One group acted as untreated control, another one was therapeutically treated with the recommended dosage. The third and fourth group were exposed to different "carry-over dosages" for three weeks, 3% of the recommended dosage were applied to the third and 10% to the fourth group. To determine the influence of a therapeutic treatment on a prestressed microbiota, both groups were treated with the recommended dosage for five days. The present study demonstrates that every kind of exposure of the commensal microbiota of poultry with enrofloxacin leads to an amplification and selection of resistant E. coli, which persist in the commensal microbiota. A long-term exposure of gut microbiota, which already harbour non-wild type E. coli, with high levels of carry-over of fluoroquinolones may lead to a development of high-level clinically

  3. Numerical simulation of an initial tsunami waveform based on sea-level data inversion: case study for the Shicotan event of the 4th October 1994

    NASA Astrophysics Data System (ADS)

    Voronina, T.

    2012-04-01

    The recent disaster of Japanese tsunami in March 2011, which caused nearly 16,000 deaths and estimated at US35-billion to US40-billion the insured cost, served as a last wake-up call to world community. Since then, the development of technology of an early warning system including methods for forecasting in real-time the tsunami waves propagation has provided a way to mitigate the adverse impacts of future tsunamis. The development of tsunami simulation models makes it possible to identify regions at tsunami risk. One of the most important issues of the tsunami modeling is gaining some insight of a tsunami source - the case in hand is the tsunami wave generated by the sea surface deformation. The latter is presumed to be equal to the co-seismic vertical displacement of the sea floor. This paper proposes an approach to recover initial tsunami waveform in tsunami source area based on the inversion of remote measurements of sea-level data. This inverse problem is treated as an ill-posed problem of hydrodynamic inversion with tsunami tide gauge records. Tsunami wave propagation is considered within the scope of the linear shallow-water theory. The direct problem is approximated by a finite-difference technique. The ill-posed inverse problem of recovering initial tsunami waveform is regularized by means of a least square inversion using the truncated SVD approach. The numerical simulating yields the so-called r-solution. The algorithm is verified with bathymetry data of the Sea of Okhotsk, synthetic and real records. In this paper, we make an attempt to answer the following questions: (1) How accurately can a tsunami source be recovered using recordings at a given tide gauge network? (2) Is it possible to improve the quality of recovering a tsunami source by distinguishing the "most informative" part of the given observation system? For answering these questions, we have carried out a series of numerical experiments. Based on the characteristics of a given tide gauges

  4. Academic writing in a corpus of 4th grade science notebooks: An analysis of student language use and adult expectations of the genres of school science

    NASA Astrophysics Data System (ADS)

    Esquinca, Alberto

    This is a study of language use in the context of an inquiry-based science curriculum in which conceptual understanding ratings are used split texts into groups of "successful" and "unsuccessful" texts. "Successful" texts could include known features of science language. 420 texts generated by students in 14 classrooms from three school districts, culled from a prior study on the effectiveness of science notebooks to assess understanding, in addition to the aforementioned ratings are the data sources. In science notebooks, students write in the process of learning (here, a unit on electricity). The analytical framework is systemic functional linguistics (Halliday and Matthiessen, 2004; Eggins, 2004), specifically the concepts of genre, register and nominalization. Genre classification involves an analysis of the purpose and register features in the text (Schleppegrell, 2004). The use of features of the scientific academic register, namely the use relational processes and nominalization (Halliday and Martin, 1993), requires transitivity analysis and noun analysis. Transitivity analysis, consisting of the identification of the process type, is conducted on 4737 ranking clauses. A manual count of each noun used in the corpus allows for a typology of nouns. Four school science genres, procedures, procedural recounts reports and explanations, are found. Most texts (85.4%) are factual, and 14.1% are classified as explanations, the analytical genre. Logistic regression analysis indicates that there is no significant probability that the texts classified as explanation are placed in the group of "successful" texts. In addition, material process clauses predominate in the corpus, followed by relational process clauses. Results of a logistic regression analysis indicate that there is a significant probability (Chi square = 15.23, p < .0001) that texts with a high rate of relational processes are placed in the group of "successful" texts. In addition, 59.5% of 6511 nouns are

  5. Transport of gemifloxacin, a 4th generation quinolone antibiotic, in the Caco-2 and engineered MDCKII cells, and potential involvement of efflux transporters in the intestinal absorption of the drug.

    PubMed

    Jin, Hyo-Eon; Song, Boran; Kim, Sang-Bum; Shim, Won-Sik; Kim, Dae-Duk; Chong, Saeho; Chung, Suk-Jae; Shim, Chang-Koo

    2013-04-01

    The oral (po) bioavailability of gemifloxacin mesylate in rats and its possible association with efflux transporters was investigated. The apparent permeabilities (Papp) of gemifloxacin across the Caco-2 cell monolayer were 1.20 ± 0.09 × 10(-5) cm/s for apical to basal (absorptive) transport, and 2.13 ± 0.6 × 10(-5) cm/s for basal to apical (secretory) transport for a 5-500 μM concentration range, suggesting the involvement of a carrier-mediated efflux in the secretory transport. The secretory transport in Caco-2 cells was significantly decreased by MRP2 (MK571) and BCRP (Ko143) inhibitors. The secretory transport was distinct in MDCKII/P-gp, MDCKII/MRP2 and MDCKII/BCRP cells, and the affinity was highest for MRP2, followed by BCRP and P-gp. The efflux was significantly decreased by verapamil and Ko143, but not significantly by MK571. The comparative po bioavailability in rats was increased by the preadministration of Ko143 (four-fold), MK571 (two-fold) and verapamil (two-fold). Efflux transporters appeared to significantly limit the bioavailability of gemifloxacin in rats, suggesting their possible contribution to the low bioavailability of the drug in the human (70%).

  6. Prevalence and Quinolone Susceptibilities of Salmonella Isolated from the Feces of Preharvest Cattle Within Feedlots that Used a Fluoroquinolone to Treat Bovine Respiratory Disease.

    PubMed

    Smith, Ashley B; Renter, David G; Cernicchiaro, Natalia; Shi, Xiaorong; Nagaraja, Tiruvoor G

    2016-06-01

    Salmonella is an important foodborne pathogen and antimicrobial resistance can be a human health concern. The objectives of this cross-sectional study were to (1) determine the prevalence and quinolone susceptibility of Salmonella in feces of preharvest commercial feedlot cattle and (2) determine if the prevalence and susceptibility of Salmonella isolates were associated with previous fluoroquinolone use within pens. Five feedlots in western Kansas and Texas were selected based on their use of a commercially licensed fluoroquinolone for initial treatment of bovine respiratory disease (BRD). Twenty pen floor fecal samples were collected from each of 10 pens from each feedlot during early summer of 2012. Salmonella isolation was performed and microbroth dilution was used to determine susceptibility of isolates to nalidixic acid and ciprofloxacin. Prior antimicrobial treatment data were retrieved from feedlots' operational data. Generalized linear mixed models were used to assess associations between Salmonella prevalence and the number of fluoroquinolone treatments within pens while taking into consideration cattle demographic and management factors, as well as the hierarchical structure of the data. Overall, cumulative fecal prevalence of Salmonella was 38.0% (380/1000), but prevalence varied significantly (p < 0.01) among the five feedlots: 0.5% (1/200), 17.5% (35/200), 37.0% (74/200), 58.5% (117/200), and 76.5% (153/200). Salmonella serogroups included C1 (49.3%), E (36.4%), C2 (13.8%), and D (0.6%). There was no significant association (p = 0.52) between Salmonella prevalence and the frequency of fluoroquinolone treatments within a pen. All Salmonella isolates (n = 380) were susceptible to ciprofloxacin, while one isolate exceeded the human breakpoint (≥32 μg/mL) for nalidixic acid. In conclusion, Salmonella fecal prevalence in preharvest cattle was highly variable among feedlots. Nearly all Salmonella isolates were susceptible to quinolones

  7. Prevalence and Quinolone Susceptibilities of Salmonella Isolated from the Feces of Preharvest Cattle Within Feedlots that Used a Fluoroquinolone to Treat Bovine Respiratory Disease.

    PubMed

    Smith, Ashley B; Renter, David G; Cernicchiaro, Natalia; Shi, Xiaorong; Nagaraja, Tiruvoor G

    2016-06-01

    Salmonella is an important foodborne pathogen and antimicrobial resistance can be a human health concern. The objectives of this cross-sectional study were to (1) determine the prevalence and quinolone susceptibility of Salmonella in feces of preharvest commercial feedlot cattle and (2) determine if the prevalence and susceptibility of Salmonella isolates were associated with previous fluoroquinolone use within pens. Five feedlots in western Kansas and Texas were selected based on their use of a commercially licensed fluoroquinolone for initial treatment of bovine respiratory disease (BRD). Twenty pen floor fecal samples were collected from each of 10 pens from each feedlot during early summer of 2012. Salmonella isolation was performed and microbroth dilution was used to determine susceptibility of isolates to nalidixic acid and ciprofloxacin. Prior antimicrobial treatment data were retrieved from feedlots' operational data. Generalized linear mixed models were used to assess associations between Salmonella prevalence and the number of fluoroquinolone treatments within pens while taking into consideration cattle demographic and management factors, as well as the hierarchical structure of the data. Overall, cumulative fecal prevalence of Salmonella was 38.0% (380/1000), but prevalence varied significantly (p < 0.01) among the five feedlots: 0.5% (1/200), 17.5% (35/200), 37.0% (74/200), 58.5% (117/200), and 76.5% (153/200). Salmonella serogroups included C1 (49.3%), E (36.4%), C2 (13.8%), and D (0.6%). There was no significant association (p = 0.52) between Salmonella prevalence and the frequency of fluoroquinolone treatments within a pen. All Salmonella isolates (n = 380) were susceptible to ciprofloxacin, while one isolate exceeded the human breakpoint (≥32 μg/mL) for nalidixic acid. In conclusion, Salmonella fecal prevalence in preharvest cattle was highly variable among feedlots. Nearly all Salmonella isolates were susceptible to quinolones

  8. A Novel Gene Amplification Causes Upregulation of the PatAB ABC Transporter and Fluoroquinolone Resistance in Streptococcus pneumoniae

    PubMed Central

    Baylay, Alison J.; Ivens, Alasdair

    2015-01-01

    Overexpression of the ABC transporter genes patA and patB confers efflux-mediated fluoroquinolone resistance in Streptococcus pneumoniae and is also linked to pneumococcal stress responses. Although upregulation of patAB has been observed in many laboratory mutants and clinical isolates, the regulatory mechanisms controlling expression of these genes are unknown. In this study, we aimed to identify the cause of high-level constitutive overexpression of patAB in M184, a multidrug-resistant mutant of S. pneumoniae R6. Using a whole-genome transformation and sequencing approach, we identified a novel duplication of a 9.2-kb region of the M184 genome which included the patAB genes. This duplication did not affect growth and was semistable with a low segregation rate. The expression levels of patAB in M184 were much higher than those that could be fully explained by doubling of the gene dosage alone, and inactivation of the first copy of patA had no effect on multidrug resistance. Using a green fluorescent protein reporter system, increased patAB expression was ascribed to transcriptional read-through from a tRNA gene upstream of the second copy of patAB. This is the first report of a large genomic duplication causing antibiotic resistance in S. pneumoniae and also of a genomic duplication causing antibiotic resistance by a promoter switching mechanism. PMID:25779578

  9. Solvent-free microwave-assisted extraction of fluoroquinolones from soil and liquid chromatography-fluorescence determination.

    PubMed

    Sturini, Michela; Speltini, Andrea; Maraschi, Federica; Rivagli, Elisa; Profumo, Antonella

    2010-11-19

    Presented hereafter is a novel method entailing solvent free microwave-assisted extraction (MAE) and HPLC equipped with Fluorimetric Detector (HPLC-FD) for the simultaneous determination at μgkg(-1) concentration of eight fluoroquinolone antibiotics (FQs) (Ciprofloxacin, Danofloxacin, Enrofloxacin, Flerofloxacin, Levofloxacin, Marbofloxacin, Norfloxacin and Orbifloxacin) in agricultural soils. The extraction was quantitatively performed, in a single step, by using an aqueous solution containing Mg(II) as complexing agent, thus avoiding consumption of organic solvents. The optimal MAE conditions have been established through a chemometric approach by considering temperature, irradiation time and matrix moisture or solvent, as the most important recognized variables affecting the extraction yield. Satisfying recoveries (69-110%, spikes 0.03-0.5mgkg(-1)) were gained with a single MAE cycle of 20min, at 80°C in 20% (w/v) Mg(NO(3))(2) solution as leaching agent. MAE-SPE recoveries at 10μgkg(-1), concentration near method quantification limits (MQLs), were in the range 60-85%. Good repeatability and within-lab reproducibility were observed (both in the range 1-16%). The applicability of the method to real samples was assessed on natural contaminated soils. Compared to ultrasonic-assisted extraction (UAE), MAE was shown to be highly competitive in terms of extraction efficacy and analysis speed.

  10. Farm level risk factors for fluoroquinolone resistance in E. coli and thermophilic Campylobacter spp. on poultry farms.

    PubMed

    Taylor, N M; Wales, A D; Ridley, A M; Davies, R H

    2016-10-01

    Data on husbandry practices, performance, disease and drug use were collected during a cross-sectional survey of 89 poultry meat farms in England and Wales to provide information on possible risk factors for the occurrence of fluoroquinolone (FQ)-resistant bacteria. Faeces samples were used to classify farms as "affected" or "not affected" by FQ-resistant (FQr) Escherichia coli or Campylobacter spp. Risk factor analysis identified the use of FQ on the farms as having by far the strongest association, among the factors considered, with the occurrence of FQr bacteria. Resistant E. coli and/or Campylobacter spp. were found on 86% of the farms with a history of FQ use. However, a substantial proportion of farms with no history of FQ use also yielded FQr organisms, suggesting that resistant bacteria may transfer between farms. Further analysis suggested that for Campylobacter spp., on-farm hygiene, cleaning and disinfection between batches of birds and wildlife control were of most significance. By contrast, for E. coli biosecurity from external contamination was of particular importance, although the modelling indicated that other factors were likely to be involved. Detailed studies on a small number of sites showed that FQr E. coli can survive routine cleaning and disinfection. It appears difficult to avoid the occurrence of resistant bacteria when FQ are used on a farm, but the present findings provide evidence to support recommendations to reduce the substantial risk of the incidental acquisition of such resistance by farms where FQ are not used. PMID:27171857

  11. Aluminium sensitized spectrofluorimetric determination of fluoroquinolones in milk samples coupled with salting-out assisted liquid-liquid ultrasonic extraction

    NASA Astrophysics Data System (ADS)

    Xia, Qinghai; Yang, Yaling; Liu, Mousheng

    2012-10-01

    An aluminium sensitized spectrofluorimetric method coupled with salting-out assisted liquid-liquid ultrasonic extraction for the determination of four widely used fluoroquinolones (FQs) namely norfloxacin (NOR), ofloxacin (OFL), ciprofloxacin (CIP) and gatifloxacin (GAT) in bovine raw milk was described. The analytical procedure involves the fluorescence sensitization of aluminium (Al3+) by complexation with FQs, salting-out assisted liquid-liquid ultrasonic extraction (SALLUE), followed by spectrofluorometry. The influence of several parameters on the extraction (the salt species, the amount of salt, pH, temperature and phase volume ratio) was investigated. Under optimized experimental conditions, the detection limits of the method in milk varied from 0.009 μg/mL for NOR to 0.016 μg/mL for GAT (signal-to-noise ratio (S/N) = 3). The relative standard deviations (RSD) values were found to be relatively low (0.54-2.48% for four compounds). The calibration graph was linear from 0.015 to 2.25 μg/mL with coefficient of determinations not less than 0.9974. The methodology developed was applied to the determination of FQs in bovine raw milk samples. The main advantage of this method is simple, accurate and green. The method showed promising applications for analyzing polar analytes especially polar drugs in various sample matrices.

  12. Lack of inhibitory effects of several fluoroquinolones on cytochrome P-450 3A activities at clinical dosage in dogs.

    PubMed

    Regmi, N L; Abd El-Aty, A M; Kubota, R; Shah, S S; Shimoda, M

    2007-02-01

    Inhibitory effects of several fluoroquinolones (FQs) on liver CYP3A activities were examined by in vitro and in vivo tests in dogs. Midazolam (MDZ) hydroxylation rate was used to determine the CYP3A activities in liver microsomes. Enrofloxacin (EFX), ofloxacin (OFX) orbifloxacin (OBFX) and ciprofloxacin (CFX) were tested. None of the FQs changed Vmax, Km or intrinsic clearance (Vmax/Km) of MDZ. For in vivo test, we examined the effects of oral administration of EFX and OFX on the pharmacokinetics of quinidine (QN), a CYP3A substrate. EFX or OFX (10 mg/kg) was administered once a day for 3 days. QN (2 mg/kg) was intravenously injected at 2 h after the final dose of FQs administration. The same dose of QN was intravenously injected 3 weeks before the start of FQs administration for control. Neither EFX nor OFX changed the pharmacokinetic parameters of QN. These in vitro and in vivo consisted results suggest that these FQs lack the inhibitory effects on CYP3A activities in dogs. Hence, given these results, the risk of drug-drug interaction is unlikely to occur between FQs and CYP3A substrates in clinical situation in dogs.

  13. Genomic Epidemiology of Gonococcal Resistance to Extended-Spectrum Cephalosporins, Macrolides, and Fluoroquinolones in the United States, 2000–2013

    PubMed Central

    Grad, Yonatan H.; Harris, Simon R.; Kirkcaldy, Robert D.; Green, Anna G.; Marks, Debora S.; Bentley, Stephen D.; Trees, David; Lipsitch, Marc

    2016-01-01

    Background. Treatment of Neisseria gonorrhoeae infection is empirical and based on population-wide susceptibilities. Increasing antimicrobial resistance underscores the potential importance of rapid diagnostic tests, including sequence-based tests, to guide therapy. However, the usefulness of sequence-based diagnostic tests depends on the prevalence and dynamics of the resistance mechanisms. Methods. We define the prevalence and dynamics of resistance markers to extended-spectrum cephalosporins, macrolides, and fluoroquinolones in 1102 resistant and susceptible clinical N. gonorrhoeae isolates collected from 2000 to 2013 via the Centers for Disease Control and Prevention's Gonococcal Isolate Surveillance Project. Results. Reduced extended-spectrum cephalosporin susceptibility is predominantly clonal and associated with the mosaic penA XXXIV allele and derivatives (sensitivity 98% for cefixime and 91% for ceftriaxone), but alternative resistance mechanisms have sporadically emerged. Reduced azithromycin susceptibility has arisen through multiple mechanisms and shows limited clonal spread; the basis for resistance in 36% of isolates with reduced azithromycin susceptibility is unclear. Quinolone-resistant N. gonorrhoeae has arisen multiple times, with extensive clonal spread. Conclusions. Quinolone-resistant N. gonorrhoeae and reduced cefixime susceptibility appear amenable to development of sequence-based diagnostic tests, whereas the undefined mechanisms of resistance to ceftriaxone and azithromycin underscore the importance of phenotypic surveillance. The identification of multidrug-resistant isolates highlights the need for additional measures to respond to the threat of untreatable gonorrhea. PMID:27638945

  14. Radiosterilization of fluoroquinolones and cephalosporins: assessment of radiation damage on antibiotics by changes in optical property and colorimetric parameters.

    PubMed

    Singh, Babita; Parwate, D V; Shukla, S K

    2009-01-01

    A most common problem encountered in radiosterilization of solid drugs is discoloration or yellowing. By pharmacopoeia method, discoloration can be assessed by measuring absorbance of solutions of irradiated solid samples at 450 nm. We propose to evaluate discoloration of solid samples directly by recording their diffuse reflectance spectra. Further, the reflectance spectrum is used to compute various color parameters: CIE XYZ tristimulus value, CIE Lab, DeltaE*(ab) (color difference), yellowness index (YI), dominant wavelength, and excitation purity by CIE method. The investigation of difference reflectance spectra and color parameters revealed that for fluoroquinolones, e-beam was more damaging than gamma radiation, whereas for cephalosporins, trend was reversed. The quantum of discoloration with gamma radiation and e-beam is found to be nearly equal when assessed by pharmacopeia method, and it is therefore inadequate to assess small color differences. The color parameters DeltaE*(ab) and DeltaYI are found to be reliable indicators of discoloration. The tolerance limits proposed in terms of DeltaE*(ab) and DeltaYI are +/-2 and +/-10 U, respectively. The dominant wavelength for all compounds has shifted to higher values indicating change in hue but defining color tolerance limit with this parameter requires adjunct excitation purity value.

  15. Simultaneous determination of fluoroquinolones in environmental water by liquid chromatography-tandem mass spectrometry with direct injection: A green approach.

    PubMed

    Denadai, Marina; Cass, Quezia Bezerra

    2015-10-30

    This work describes an on-line multi-residue method for simultaneous quantification of ciprofloxacin, enrofloxacin, gemifloxacin, moxifloxacin, norfloxacin and ofloxacin in superficial and wastewater samples. For that, an octyl restricted-access media bovine serum albumin column (RAM-BSA C8) was used for sample clean-up, enrichment and analysis with quantitation carried out by tandem mass spectrometry. For water samples volumes of only 500μL the method provided good selectivity, extraction efficiency, accuracy, and precision with quantification limits in the order of 20-150ngL(-1). Out of the six fluoroquinolones only ciprofloxacin (195ngL(-1)) and norfloxacin (270ngL(-1)) were quantified in an influent sample of the wastewater treatment plant (WWTP) of São Carlos (SP, Brazil). None were found in the superficial water samples analyzed. The capability of injecting native sample in an automated mode provides high productivity and represents a greener approach in environmental sample analysis.

  16. Simultaneous determination of seven fluoroquinolones in royal jelly by ultrasonic-assisted extraction and liquid chromatography with fluorescence detection.

    PubMed

    Zhou, Jinhui; Xue, Xiaofeng; Chen, Fang; Zhang, Jinzhen; Li, Yi; Wu, Liming; Chen, Lanzhen; Zhao, Jing

    2009-04-01

    A method for the quantitative determination of seven fluoroquinolone antibacterial agents (FQs) used in beekeeping, viz. ciprofloxacin, norfloxacin, ofloxacin, pefloxacin, danofloxacin, enrofloxacin, and difloxacin, in royal jelly samples was developed on the basis of high performance liquid chromatography with fluorescence detection. Sample preparation included deproteination, ultrasonic-assisted extraction with a mixed inorganic solution of monopotassium phosphate (KH(2)PO(4)) and ethylenediaminetetraacetic acid disodium salt (Na(2)EDTA), and clean-up on a solid-phase extraction cartridge. The extraction procedure was optimized with regard to the amount of inorganic solvent and the duration of sonication for royal jelly as a complicated matrix. Overall recoveries for FQs ranged from 85.9 to 99.1% for royal jelly with standard deviations between 2.79 and 6.27%. Limits of quantification were 2-40 ng/g for seven FQs in royal jelly. A total of 57 real royal jelly samples collected from beekeepers and supermarkets were analyzed. The three most abundant honeybee-use FQs, i. e. ofloxacin, ciprofloxacin, and norfloxacin, were determined in some royal jelly samples in concentrations ranging from 11.9 to 55.6 ng/g. Unexpectedly, however, difloxacin was found at concentrations of about 46.8 ng/g in one sample although it is rarely used in beekeeping. The presented method was successfully applied to quantify FQs in real royal jelly samples.

  17. Antimicrobial and antifouling efficacy of urinary catheters impregnated with a combination of macrolide and fluoroquinolone antibiotics against Pseudomonas aeruginosa.

    PubMed

    Saini, Hina; Chhibber, Sanjay; Harjai, Kusum

    2016-01-01

    The incidence of catheter associated urinary tract infections (CAUTIs) is increasing worldwide. This study was designed to modify a biomaterial by impregnating a silicone urinary catheter with combination of a macrolide, azithromycin (AZM) and a fluoroquinolone, ciprofloxacin (CIP). Drug release profiles showed slow yet continuous release of antibiotics from catheters for one month. In vitro efficacy testing showed that group B catheters [3% (w v(-1)) CIP + 6% (w v(-1)) AZM] outperformed group A catheters [2% (w v(-1)) CIP + 5% (w v(-1)) AZM] by (1) showing larger zones of inhibition (>31 mm) compared to group A (<28 mm) for up to 30 days against Pseudomonas aeruginosa PAO1; (2) killing adhered bacteria in 24 h compared to 24-48 h in group A; (3) showing longer antimicrobial durability for four weeks; and (4) exhibiting a stable real-time shelf life of one year, suggesting that these catheters can be explored in clinical settings, especially in long-term CAUTI. PMID:26982572

  18. Farm level risk factors for fluoroquinolone resistance in E. coli and thermophilic Campylobacter spp. on poultry farms.

    PubMed

    Taylor, N M; Wales, A D; Ridley, A M; Davies, R H

    2016-10-01

    Data on husbandry practices, performance, disease and drug use were collected during a cross-sectional survey of 89 poultry meat farms in England and Wales to provide information on possible risk factors for the occurrence of fluoroquinolone (FQ)-resistant bacteria. Faeces samples were used to classify farms as "affected" or "not affected" by FQ-resistant (FQr) Escherichia coli or Campylobacter spp. Risk factor analysis identified the use of FQ on the farms as having by far the strongest association, among the factors considered, with the occurrence of FQr bacteria. Resistant E. coli and/or Campylobacter spp. were found on 86% of the farms with a history of FQ use. However, a substantial proportion of farms with no history of FQ use also yielded FQr organisms, suggesting that resistant bacteria may transfer between farms. Further analysis suggested that for Campylobacter spp., on-farm hygiene, cleaning and disinfection between batches of birds and wildlife control were of most significance. By contrast, for E. coli biosecurity from external contamination was of particular importance, although the modelling indicated that other factors were likely to be involved. Detailed studies on a small number of sites showed that FQr E. coli can survive routine cleaning and disinfection. It appears difficult to avoid the occurrence of resistant bacteria when FQ are used on a farm, but the present findings provide evidence to support recommendations to reduce the substantial risk of the incidental acquisition of such resistance by farms where FQ are not used.

  19. YVUN Celebrates Its 4th Year!

    ERIC Educational Resources Information Center

    Yonka, Patricia

    2006-01-01

    This article discusses the formation of the Youth Visits the United Nations (YVUN) program. The program began in 2003 with funds provided by the Ursula Thrush Peace Seed Grant. Its purpose is to bring middle school students to New York to attend sessions of the United Nations, allowing these adolescents the opportunity to learn about global issues…

  20. Seismic Waves, 4th order accurate

    SciTech Connect

    2013-08-16

    SW4 is a program for simulating seismic wave propagation on parallel computers. SW4 colves the seismic wave equations in Cartesian corrdinates. It is therefore appropriate for regional simulations, where the curvature of the earth can be neglected. SW4 implements a free surface boundary condition on a realistic topography, absorbing super-grid conditions on the far-field boundaries, and a kinematic source model consisting of point force and/or point moment tensor source terms. SW4 supports a fully 3-D heterogeneous material model that can be specified in several formats. SW4 can output synthetic seismograms in an ASCII test format, or in the SAC finary format. It can also present simulation information as GMT scripts, whixh can be used to create annotated maps. Furthermore, SW4 can output the solution as well as the material model along 2-D grid planes.