Science.gov

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. Plasma-based studies on 4th generation light sources

    NASA Astrophysics Data System (ADS)

    Lee, R. W.; Baldis, H. A.; Cauble, R. C.; Landen, O. L.; Wark, J. S.; Ng, A.; Rose, S. J.; Lewis, C.; Riley, D.; Gauthier, J.-C.; Audebert, P.

    2001-08-01

    The construction of a short pulse tunable x-ray laser source will be a watershed for plasma-based and warm dense matter research. The areas we will discuss below can be separated broadly into warm dense matter (WDM) research, laser probing of near solid density plasmas, and laser-plasma spectroscopy of ions in plasmas. The area of WDM refers to that part of the density-temperature phase space where the standard theories of condensed matter physics and/or plasma statistical physics are invalid. Warm dense matter, therefore, defines a region between solids and plasmas, a regime that is found in planetary interiors, cool dense stars, and in every plasma device where one starts from a solid, e.g., laser-solid matter produced plasma as well as all inertial fusion schemes. The study of dense plasmas has been severely hampered by the fact that laser-based methods have been unavailable. The single most useful diagnostic of local plasma conditions, e.g., the temperature (Te), the density (ne), and the ionization (Z), has been Thomson scattering. However, due to the fact that visible light will not propagate at electron densities, ne⩾1022cm-3 implies dense plasmas can not be probed. The 4th generation sources, LCLS and Tesla will remove these restrictions. Laser-based plasma spectroscopic techniques have been used with great success to determine the line shapes of atomic transitions in plasmas, study the population kinetics of atomic systems embedded in plasmas, and look at redistribution of radiation. However, the possibilities end for plasmas with ne⩾1022 since light propagation through the medium is severely altered by the plasma. The entire field of high Z plasma kinetics from laser produced plasma will then be available to study with the tunable source.

  3. Plasma-Based Studies on 4th Generation Light Sources

    SciTech Connect

    Lee, R W; Baldis, H A; Cauble, R C; Landen, O L; Wark, J S; Ng, A; Rose, S J; Lewis, C; Riley, D; Gauthier, J-C; Audebert, P

    2000-11-28

    The construction of a short pulse tunable x-ray laser source will be a watershed for plasma-based and warm dense matter research. The areas we will discuss below can be separated broadly into warn dense matter (WDM) research, laser probing of near solid density plasmas, and laser-plasma spectroscopy of ions in plasmas. The area of WDM refers to that part of the density-temperature phase space where the standard theories of condensed matter physics and/or plasma statistical physics are invalid. Warm dense matter, therefore, defines a region between solids and plasmas, a regime that is found in planetary interiors, cool dense stars, and in every plasma device where one starts from a solid, e.g., laser-solid matter produced plasma as well as all inertial fusion schemes. The study of dense plasmas has been severely hampered by the fact that laser-based methods have been unavailable. The single most useful diagnostic of local plasma conditions, e.g., the temperature (T{sub e}), the density (n{sub e}), and the ionization (Z), has been Thomson scattering. However, due to the fact that visible light will not propagate at electron densities, n{sub e}, {ge} 10{sup 22} cm{sup -3} implies dense plasmas can not be probed. The 4th generation sources, LCLS and Tesla will remove these restrictions. Laser-based plasma spectroscopic techniques have been used with great success to determine the line shapes of atomic transitions in plasmas, study the population kinetics of atomic systems embedded in plasmas, and look at redistribution of radiation. However. the possibilities end for plasmas with n{sub e} {ge} 10{sup 22} since light propagation through the medium is severely altered by the plasma. The entire field of high Z plasma kinetics from laser produced plasma will then be available to study with the tunable source.

  4. 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.

  5. 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.

  6. 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.

  7. Fluoroquinolone susceptibility in Mycobacterium tuberculosis after pre-diagnosis exposure to older- versus newer-generation fluoroquinolones.

    PubMed

    van der Heijden, Yuri F; Maruri, Fernanda; Blackman, Amondrea; Mitchel, Ed; Bian, Aihua; Shintani, Ayumi K; Eden, Svetlana; Warkentin, Jon V; Sterling, Timothy R

    2013-09-01

    Fluoroquinolone exposure before tuberculosis (TB) diagnosis is common. We anticipated that exposure to older-generation fluoroquinolones is associated with greater fluoroquinolone MICs in Mycobacterium tuberculosis than exposure to newer agents. A nested case-control study was performed among newly diagnosed TB patients reported to the Tennessee Department of Health (January 2002-December 2009). Each fluoroquinolone-resistant case (n=25) was matched to two fluoroquinolone-susceptible controls (n=50). Ciprofloxacin and ofloxacin were classified as older-generation fluoroquinolones; levofloxacin, moxifloxacin and gatifloxacin were considered newer agents. There was no difference between median ofloxacin MIC for isolates from 9 patients exposed only to older fluoroquinolones, 25 exposed only to newer fluoroquinolones, 6 exposed to both and 35 fluoroquinolone-unexposed patients (Kruskal-Wallis, P=0.35). Using multivariate proportional odds logistic regression adjusting for age and sex, duration of exposure to newer fluoroquinolones was independently associated with higher MIC (OR=1.79, 95% CI 1.22-2.64), but duration of exposure to older fluoroquinolones was not (OR=0.94, 95% CI 0.50-1.78). Isolates from patients exposed only to newer fluoroquinolones tended to have mutations at gyrA codons 90, 91 or 94 more frequently than those exposed only to older fluoroquinolones (44% vs. 11%). We were surprised to find that duration of exposure to newer fluoroquinolones, but not older ones, was independently associated with higher ofloxacin MIC. This suggests that the mutant selection window lower boundary is likely to have clinical relevance; caution is warranted when newer fluoroquinolones are prescribed to patients with TB risk factors.

  8. 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.

  9. Enhanced distribution of fourth-generation fluoroquinolones in prostatic tissue.

    PubMed

    Perletti, G; Wagenlehner, F M E; Naber, K G; Magri, V

    2009-03-01

    A recently published pharmacokinetic trial showed that the fluoroquinolone moxifloxacin administered to healthy volunteers at the single oral dose of 400mg accumulates in prostatic secretions (PS) up to a median concentration of 3.99 mg/L and reaches a PS/plasma concentration ratio of 1.57, far higher than values shown by other fluoroquinolones such as norfloxacin (ratio 0.1) or ciprofloxacin (ratio 0.2). Ion trapping mechanisms were hypothesised to be among the determinants of this effect. However, whether ion trapping would solely account for the observed differences in fluoroquinolone pharmacokinetics was left to further research and discussion. In this hypothesis paper, we review various published evidence on the tissue distribution of moxifloxacin and other quinolones, suggesting that increased lipophilicity, binding to cellular matrices and fast cellular uptake/release kinetics may be mechanisms compatible with enhanced prostatic accumulation and secretion of fourth-generation fluoroquinolones.

  10. [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.

  11. 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.

  12. 4th generation HIV screening in Massachusetts: a partnership between laboratory and program.

    PubMed

    Goodhue, Tammy; Kazianis, Arthur; Werner, Barbara G; Stiles, Tracy; Callis, Barry P; Dawn Fukuda, H; Cranston, Kevin

    2013-12-01

    The Massachusetts Department of Public Health's (MDPH) Office of HIV/AIDS (OHA) and Hinton State Laboratory Institute (HSLI) have offered HIV screening since 1985. Point-of-care screening and serum collection for laboratory-based testing is conducted at clinic and non-clinic-based sites across Massachusetts as part of an integrated communicable disease screening intervention. MDPH aimed to transition to a 4th generation HIV screening-based algorithm for testing all serum specimens collected at OHA-funded programs and submitted to the HSLI to detect acute HIV infections, detect and differentiate HIV-1 and HIV-2 infections, eliminate indeterminate results, reduce cost and turnaround time, and link newly diagnosed HIV+ individuals to care. The HSLI and OHA created a joint project management team to plan and lead the transition. The laboratory transitioned successfully to a 4th generation screening assay as part of a revised diagnostic algorithm. In the 12 months since implementation, a total of 7984 serum specimens were tested with 258 (3.2%) positive for HIV-1 and one positive for HIV-2. Eight were reported as acute HIV-1 infections. These individuals were linked to medical care and partner services in a timely manner. Turnaround time was reduced and the laboratory realized an overall cost savings of approximately 15%. The identification of eight acute HIV infections in the first year underscores the importance of using the most sensitive screening tests available. A multi-disciplinary program and laboratory team was critical to the success of the transition, and the lessons learned may be useful for other jurisdictions. Published by Elsevier B.V.

  13. [Analysis of the 4th generation Scutellaria baicalensis Georgi with space mutagenesis via FTIR spectroscopy].

    PubMed

    Ding, Xi-feng; Gao, Hua-na; Guo, Xi-hua; Wang, Zhi-zhou; Yang, La-huz; Guan, Ying; Shi, Jin-shan

    2009-05-01

    Determination and analysis for the Scutellaria baicalensis Georgi with space mutagenesis and the ground group were carried out with FTIR for the first time in order to fully understand the quality changes of the 4th generation of space mutagenesis of Scutellaria baicalensis Georgi and do further research. The result shows that for the FTIR spectra of the two samples the position and shape of main absorption peaks are approximately the same, indicating that the major components and the structures of space group remain intact, but the intensities of the absorption peaks are obviously different, with the intensities of the space group significantly enhanced compared to the ground group, especially for the flavonoid compounds (baicalin, baicalein, wogonoside, wogonin and wogonoside etc), which are the main active components of the Scutellaria baicalensis Georgi, the absorption peak intensities at 3391, 1655 and 1069 cm(-1) are obviously stronger than those of the ground group, so the contents of flavonoid compounds and other components are higher, and the amorphous active components are optimized. Space mutation breeding is conducive to breeding new varieties of highly active components, and it is also one of the ways to innovate Chinese medicines germplasm resources efficiently.

  14. 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

  15. Skin and skin structure infections: treatment with newer generation fluoroquinolones

    PubMed Central

    Giordano, Philip; Weber, Kurt; Gesin, Gail; Kubert, Jason

    2007-01-01

    Skin and skin structure infections (SSSI) are an emerging issue in healthcare. They are responsible for increasing heathcare utilization, both in hospitalizations and intravenous antibiotic use. SSSI are caused by an evolving variety of pathogens, including Gram-positive, Gram-negative, and anaerobic bacteria. In combination with mounting resistance patterns, this diverse range of bacteria mandate empiric broad-spectrum antibiotic coverage. Historically, cephalosporins and penicillins have been the mainstay of treatment, but recent data suggest newer generation fluoroquinolones are being used with increasing frequency. In 2005, moxifloxacin joined gatifloxacin and levofloxacin as newer generation fluoroquionolones with Food and Drug Administration indications for SSSIs. Even within this group there exist subtle differences that impact optimal management. This paper offers the clinician a comparative review of the antimicrobial spectrum, pharmacodynamics, pharmacokinetics, and clinical efficacy data to support the appropriate use of fluoroquinolones in SSSIs. PMID:18360639

  16. 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.

  17. 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.

  18. [Bacterial enteric pathogens' resistance to fluoroquinolones and last generation cephalosporines].

    PubMed

    Damian, Maria; Usein, Codruţa-Romanita; Palade, Andi Marian; Băltoiu, Mădălina; Condei, Maria; Ciontea, Simona; Tatu-Chiţoiu, Dorina

    2010-01-01

    The increase of incidence of resistance to the antibiotics became the most worrisome subject within the clinical and research communities in the medical fields. Intrinsic resistance genetic mutations, horizontal transfer of mobile structures carrying genes coding for resistance to the antibiotics within the pan-microbial genome are representing the bacterial resistome which is bearing the genetic information regarding the defensive mechanisms developed by micro-organisms to protect themselves against antibiotics. Rice in the resistance of enteric bacteria, pathogens involved in a large number of human infections, to the cephalosporin of last generation and to the fluoroquinolones is a very actual subject in the medical area. Production of beta-lactamases with extended spectrum is the most important enzymatic defence system, developed by micro-organisms, consisting in the inactivation of beta-lactam antibiotics by destroying the beta-lactam ring. Enterobacteria are able to produce beta-lactamases of type TEM, SHV and/or CTX-M. Punctual mutations in nucleotide structure of bla genes, coding for beta-lactamases synthesis, are leading on production of a large diversity of enzymes with enlarged spectrum of activity (ESBL). At the beginning of 90's the first beta-lactamases resistance to clavulanic acid were detected and in our days more then 170 TEM, 120 SVH and 90 CTX-MESBLs are known. Escherichia coli strains are producing, firstly, TEM ESBLs, Klebsiella pneumoniae SHV ESBLs. and both are producing CTX-M type ESBLs, are resistant to the fluoroquinolones due to punctual mutations in nucleotide structure of gyr gene coding for gyrases production, enzymes involved in nucleic acids replication. Resistance to the antibiotics with extended activity is a public health threat due to their capacity of large spreading within bacterial population, when the coding structures are located on mobile genetic structures. The menace increase when genes coding for fluoroquinolones

  19. [Antidepressives of the 3rd, 4th and 5th generation].

    PubMed

    Svestka, J

    1994-02-01

    Antidepressants are classified into five generations. Preparations of the first generation affect various neurotransmitter systems and are therefore associated with many undesirable effects (e.g. tricyclic antidepressants, maprotiline). The second generation of antidepressants is already devoid of anticholinergic action and their adrenolytic and antihistaminic effects are weaker (e.g. mianserine, mirtazapine, trazodone). The antidepressant action of preparations of the third generation is mediated only by one of the three main neurotransmitter systems for depression (5-HT, noradrenaline, dopamine) and does not affect muscarine, histamine and adrenergic cerebral systems (e.g. SSRI, ipsapirone, viloxazine, reboxetine, bupropione). Recently antidepressants of the fourth generation were synthetized which influence only the serotonin, and noradrenaline or dopamine system (e.g. milnacipran, befloxatone). The fifth generation of antidepressants foresees the exclusive action on 5-HT, noradrenaline and dopamine systems of the CNS in varying ratios (e.g. venlafaxine, cericlamine).

  20. Characterization of γ and γ' phases in 2nd and 4th generation single crystal nickel-base superalloys

    NASA Astrophysics Data System (ADS)

    Zietara, Maciej; Neumeier, Steffen; Göken, Mathias; Czyrska-Filemonowicz, Aleksandra

    2017-01-01

    A Ni based single crystal superalloy from the 2nd generation, PWA 1484, and one from the 4th generation, PWA 1497, were comparatively studied by scanning electron microscopy, energy dispersive X-ray spectroscopy and nanoindentation technique in an atomic force microscope (NI-AFM) after high temperature creep deformation. During primary creep of both generations of superalloys, γ' precipitates start to coalesce and grow directionally. Further creep deformation leads to the topological inversion and coarsening of the rafted microstructure. The NI-AFM technique was used for measurements of the hardness of the γ and γ' phases in as-received and creep deformed samples in various conditions. The g matrix of the PWA 1497 superalloy is on average 0.8 GPa harder than that of PWA 1484 that can be explained by higher content of Re and Ru, since they partition predominantly to the matrix phase.

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

    SciTech Connect

    Bruni, C.; Couprie, M. E.; Chubar, O.; Loulergue, A.; Nahon, L.; Carre, B.; Garzella, D.; Labat, M.; Lambert, G.; Monot, P.; Jablonka, M.; Meot, F.; Ortega, J. M.; Nutarelli, D.

    2007-01-19

    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.

  2. 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.

  3. Battling the "Hydra": Changing Operational Factors in 4th Generation War

    DTIC Science & Technology

    2007-11-02

    challenging us to change current doctrine and attempts to reduce war to algebraic formulae. Current Operational Doctrine Operational art, as advanced...over terrain -- the image and concept of ’classic’ war. A- 2 Armies turned to ’science," relying upon mathematical probabilities and algebraic formulae...Jominian war of algebraic formula and mathematical probabilities, vice accepting the 3d generation premise to cause and thrive within chaos. Lacking

  4. Could larger diameter of 4th generation ceramic bearing decrease the rate of dislocation after THA?

    PubMed

    Lee, Young-Kyun; Ha, Yong-Chan; Jo, Woo-Lam; Kim, Tae-Young; Jung, Woon-Hwa; Koo, Kyung-Hoi

    2016-05-01

    Fourth generation (Delta) ceramic bearing was developed to reduce dislocation after total hip arthroplasty (THA) by increasing the head diameter. We tested a hypothesis that 32/36 mm Delta ceramic bearing decreases the dislocation rate. We also evaluated ceramic-related complications and early outcome of this thin liner-on-large head ceramic bearing. We performed a prospective study on patients who underwent THA with use of 32/36 mm Delta ceramic bearing. The dislocation rate was compared with the historical dislocation rate of third generation 28 mm ceramic bearing. We also evaluated ceramic fracture, squeak, short-term results and survival. Follow-up period was minimum 2 years. Between April 2010 and February 2012, we enrolled 250 consecutive patients (278 hips). All patients received cementless prostheses. Four patients (4 hips) who received metal shells ≤ 46 mm and 28 mm heads were excluded. Three patients died and 2 patients were lost within 2 years. The remaining 241 patients (269 hips) were followed for 24-46 months. There were 142 men (161 hips) and 99 women (108 hips) with a mean age of 53.7 years (range, 17-75 years) at the index operation. Dislocation occurred in three hips (1.1%). An old age was a risk factor for dislocation. Ceramic fracture and squeaking did not occur in any patient. Mean Harris hip score was 90.3 points at the latest follow-up. All acetabular and femoral components had bone-ingrowth stability. No hip had detectable wear or osteolysis. The survival was 99.3% in the best case scenario and 97.8% in the worst at 48 months. Total hip arthroplasty with use of 32/36 mm Delta ceramic bearing showed lower incidence of hip dislocation compared with 28 mm third generation ceramic bearing. A caution should be paid to prevent a fall in senile patients even though a large head is used. The short-term results of THA with this type of ceramic articulation are encouraging and we did not find any ceramic-related complications. Copyright

  5. Fluoroquinolone susceptibility in Mycobacterium tuberculosis after pre-diagnosis exposure to older- versus newer-generation fluoroquinolones☆

    PubMed Central

    van der Heijden, Yuri F.; Maruri, Fernanda; Blackman, Amondrea; Mitchel, Ed; Bian, Aihua; Shintani, Ayumi K.; Eden, Svetlana; Warkentin, Jon V.; Sterling, Timothy R.

    2013-01-01

    Fluoroquinolone exposure before tuberculosis (TB) diagnosis is common. We anticipated that exposure to older-generation fluoroquinolones is associated with greater fluoroquinolone MICs in Mycobacterium tuberculosis than exposure to newer agents. A nested case–control study was performed among newly diagnosed TB patients reported to the Tennessee Department of Health (January 2002–December 2009). Each fluoroquinolone-resistant case (n = 25) was matched to two fluoroquinolone-susceptible controls (n = 50). Ciprofloxacin and ofloxacin were classified as older-generation fluoroquinolones; levofloxacin, moxifloxacin and gatifloxacin were considered newer agents. There was no difference between median ofloxacin MIC for isolates from 9 patients exposed only to older fluoroquinolones, 25 exposed only to newer fluoroquinolones, 6 exposed to both and 35 fluoroquinolone-unexposed patients (Kruskal–Wallis, P = 0.35). Using multivariate proportional odds logistic regression adjusting for age and sex, duration of exposure to newer fluoroquinolones was independently associated with higher MIC (OR = 1.79, 95% CI 1.22–2.64), but duration of exposure to older fluoroquinolones was not (OR = 0.94, 95% CI 0.50–1.78). Isolates from patients exposed only to newer fluoroquinolones tended to have mutations at gyrA codons 90, 91 or 94 more frequently than those exposed only to older fluoroquinolones (44% vs. 11%). We were surprised to find that duration of exposure to newer fluoroquinolones, but not older ones, was independently associated with higher ofloxacin MIC. This suggests that the mutant selection window lower boundary is likely to have clinical relevance; caution is warranted when newer fluoroquinolones are prescribed to patients with TB risk factors. PMID:23806638

  6. Development of partially-coherent wavefront propagation simulation methods for 3rd and 4th generation synchrotron radiation sources

    NASA Astrophysics Data System (ADS)

    Chubar, Oleg; Berman, Lonny; Chu, Yong S.; Fluerasu, Andrei; Hulbert, Steve; Idir, Mourad; Kaznatcheev, Konstantine; Shapiro, David; Shen, Qun; Baltser, Jana

    2011-09-01

    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.

  7. 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…

  8. 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…

  9. Fourth-generation fluoroquinolone-resistant mycobacterial keratitis after laser in situ keratomileusis.

    PubMed

    Moshirfar, Majid; Meyer, Jay J; Espandar, Ladan

    2007-11-01

    We report a case of mycobacterial keratitis resistant to fourth-generation fluoroquinolones after laser in situ keratomileusis (LASIK) with fourth-generation fluoroquinolone prophylaxis. While receiving moxifloxacin post LASIK, the patient was diagnosed with moxifloxacin-resistant Mycobacterium chelonae keratitis. Culture susceptibilities revealed isolates resistant to moxifloxacin and gatifloxacin, and treatment with topical amikacin and clarithromycin with oral doxycycline and clarithromycin along with flap amputation was necessary to control the infection. This case demonstrates the potential limitations in the coverage of these antibiotic agents.

  10. Rate of bacterial eradication by ophthalmic solutions of fourth-generation fluoroquinolones.

    PubMed

    Callegan, Michelle C; Novosad, Billy D; Ramadan, Raniyah T; Wiskur, Brandt; Moyer, Andrea L

    2009-04-01

    Antibacterial activity of ophthalmic fourth-generation fluoroquinolones has traditionally been evaluated by comparing only their active ingredients, gatifloxacin and moxifloxacin. However, ophthalmic formulations of fourth-generation fluoroquinolones differ in terms of the inclusion of preservatives. While gatifloxacin ophthalmic solution 0.3% (Zymar; Allergan, Inc., Irvine, CA, USA) contains 0.005% benzalkonium chloride (BAK), moxifloxacin ophthalmic solution 0.5% (Vigamox; Alcon Laboratories, Inc., Fort Worth, TX, USA) is preservative-free. Recent studies have demonstrated that the presence of BAK dramatically affects the antibacterial activity of the ophthalmic formulation of gatifloxacin. This study was designed to compare the kill rates of ophthalmic solutions of fourth-generation fluoroquinolones against isolates of common ocular bacterial pathogens. Approximately 5.6 log(10) colony-forming units (CFU)/mL of Haemophilus influenzae (n=1), Streptococcus pneumoniae (n=1), Staphylococcus aureus (n=2), methicillin-resistant Staphylococcus aureus (MRSA) (n=4), methicillinresistant Staphylococcus epidermidis (MRSE) (n=4), and fluoroquinolone-resistant S. epidermidis (n=1) were incubated with ophthalmic solutions of either gatifloxacin or moxifloxacin. Viable bacteria were quantified at specific time points up to 60 minutes. Gatifloxacin 0.3% completely eradicated H. influenzae and Strep. pneumoniae in 5 minutes, one of two S. aureus isolates in 15 minutes, and the other S. aureus isolate in 60 minutes. Gatifloxacin 0.3% completely killed all MRSA, MRSE, and fluoroquinolone-resistant S. epidermidis isolates in 15 minutes. Moxifloxacin 0.5% completely eradicated Strep. pneumoniae and one of four MRSA isolates in 60 minutes. All other isolates incubated with moxifloxacin 0.5% retained viable bacteria ranging from 1.8 to 4.4 log(10) CFU/mL. The ophthalmic solution of gatifloxacin 0.3% eradicated bacteria that frequently cause postoperative ocular infections

  11. 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

    2008-02-04

    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%.

  12. 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.

  13. High variability among Emergency Departments in 3rd-generation cephalosporins and fluoroquinolones use for community-acquired pneumonia.

    PubMed

    Batard, Eric; Lecadet, Nathalie; Goffinet, Nicolas; Hardouin, Jean-Benoit; Lepelletier, Didier; Potel, Gilles; Montassier, Emmanuel

    2015-12-01

    Fluoroquinolones and 3rd-generation cephalosporins that are prescribed for pneumonia may be avoided and replaced by a penicillin in some cases. We aimed to determine if the proportion of patients treated for pneumonia with a cephalosporin, a fluoroquinolone or both varies among Emergency Departments (EDs), and to estimate the proportion of avoidable prescriptions. This was a retrospective study of patients treated for pneumonia in eight French EDs, and subsequently hospitalized in non-ICU wards. Third-generation cephalosporins or respiratory fluoroquinolones were presumed unavoidable if they met both criteria: (1) age ≥65 years or comorbid condition; and (2) allergy or intolerance to penicillin, or failure of penicillin, or previous treatment with penicillin, or for fluoroquinolones only, suspected legionellosis. We included 832 patients. Thirty-four percent (95 % CI, 31-38 %) of patients were treated with a cephalosporin, a respiratory fluoroquinolone or both (range among EDs 19-44 %). Four EDs were independent risk factors for prescription of a cephalosporin, a fluoroquinolone or both [adjusted OR, 2.27 (1.64-3.15)], as were immune compromise [aOR 2.54 (1.56-4.14)], antibacterial therapy started before arrival in the ED [aOR 3.32 (2.30-4.81)], REA-ICU class III or IV [aOR 1.93 (1.15-3.23)], PSI class V [aOR 1.49 (1.00-2.20)], fluid resuscitation [aOR 3.98 (2.49-6.43)] and non-invasive ventilation in the ED [aOR, 7.18 (1.7-50.1)]. Treatment with a cephalosporin, a fluoroquinolone or both was avoidable in 67 % (62-73 %) of patients. Cephalosporins and fluoroquinolones use in pneumonia is highly variable among EDs. The majority of these prescriptions are avoidable. Antibiotic stewardship programs should be implemented to restrict their use in EDs.

  14. Organization of the Topical Meeting on Short Wavelength Coherent Radiation: Generation and Applications (4th) Held in North Falmouth, Massachusetts

    DTIC Science & Technology

    1989-03-01

    spectrometer using coherent VUV generated by four -wave 8:30 AM (Invited Paper) sum mixing has been used to study autoionization in NO and MAI The A. C...tween n = 5, 4, and 3 excited levels are observed in a 100- ps TuC13 Capillary Discharge Plasmas as Extreme Ultraviolet laser-produced heliumlike Al plasma...Interference in Four -Wave TuC28 Gain Measurement on a 18.2-nm Carbon Recombin- Mixing, K. G. H. Baldwin. Australian National U. Constructive ation Laser

  15. Use of broad-spectrum antibiotics in French EDs: different trends for third-generation cephalosporins and fluoroquinolones.

    PubMed

    Batard, Eric; Vibet, Marie-Anne; Lemarchand, Cathelle; Navas, Dominique; Lepelletier, Didier; Potel, Gilles; Montassier, Emmanuel

    2017-06-01

    Third-generation cephalosporins and fluoroquinolones are particularly prone to promoting bacterial resistance. Their use in Emergency Departments (EDs) is poorly known. Our objectives were to assess the use of antibacterial agents in French EDs. This study is a retrospective study of antibiotics delivered to the adult units of 11 EDs of French academic centres in 2012, and to six of these EDs between 2009 and 2012. The total antibiotic use was 66.4 defined daily doses (DDD)/1000 ED visits in 2012, and it increased between 2009 and 2012 (yearly estimate, +1.8±0.9 DDD/1000 ED visits, P=0.048). The 3GC-FQ class, which grouped third-generation cephalosporins and fluoroquinolones, accounted for 39.2% of the total antibiotic use, and the use of this class of antibiotics was highly variable among EDs (range, 31.6-49.5% of total antibiotic use). The aminopenicillin and β-lactamase inhibitor/3GC-FQ ratio varied among EDs [median (range), 0.91 (0.52-1.25)]. Between 2009 and 2012, there was a significant decrease in the use of the 3GC-FQ class (yearly estimate, -0.8±0.4% of total antibiotic use), antipneumococcal fluoroquinolones (-0.8±0.3%) and other fluoroquinolones (-0.9%±0.3%), and there was a significant increase in the use of third-generation cephalosporins (+0.7±0.3%), aminoglycosides (+0.4±0.1%), imidazole derivatives (+0.4±0.1%) and lincosamides (+0.1±0.0%). Fluoroquinolones and third-generation cephalosporins are widely used in the ED. Their use is highly variable among EDs. Third-generation cephalosporins were increasingly used between 2009 and 2012, whereas the use of fluoroquinolones decreased. Reduced use of cephalosporins in the ED, without increasing fluoroquinolone use, should be aimed at through antibiotic stewardship programs.

  16. 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

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

    NASA Astrophysics Data System (ADS)

    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.

    2012-07-01

    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.

  18. Probing ultra-fast processes with high dynamic range at 4th-generation light sources: Arrival time and intensity binning at unprecedented repetition rates

    DOE PAGES

    Kovalev, S.; Green, B.; Golz, T.; ...

    2017-03-06

    Here, understanding dynamics on ultrafast timescales enables unique and new insights into important processes in the materials and life sciences. In this respect, the fundamental pump-probe approach based on ultra-short photon pulses aims at the creation of stroboscopic movies. Performing such experiments at one of the many recently established accelerator-based 4th-generation light sources such as free-electron lasers or superradiant THz sources allows an enormous widening of the accessible parameter space for the excitation and/or probing light pulses. Compared to table-top devices, critical issues of this type of experiment are fluctuations of the timing between the accelerator and external laser systemsmore » and intensity instabilities of the accelerator-based photon sources. Existing solutions have so far been only demonstrated at low repetition rates and/or achieved a limited dynamic range in comparison to table-top experiments, while the 4th generation of accelerator-based light sources is based on superconducting radio-frequency technology, which enables operation at MHz or even GHz repetition rates. In this article, we present the successful demonstration of ultra-fast accelerator-laser pump-probe experiments performed at an unprecedentedly high repetition rate in the few-hundred-kHz regime and with a currently achievable optimal time resolution of 13 fs (rms). Our scheme, based on the pulse-resolved detection of multiple beam parameters relevant for the experiment, allows us to achieve an excellent sensitivity in real-world ultra-fast experiments, as demonstrated for the example of THz-field-driven coherent spin precession.« less

  19. Probing ultra-fast processes with high dynamic range at 4th-generation light sources: Arrival time and intensity binning at unprecedented repetition rates

    PubMed Central

    Kovalev, S.; Green, B.; Golz, T.; Maehrlein, S.; Stojanovic, N.; Fisher, A. S.; Kampfrath, T.; Gensch, M.

    2017-01-01

    Understanding dynamics on ultrafast timescales enables unique and new insights into important processes in the materials and life sciences. In this respect, the fundamental pump-probe approach based on ultra-short photon pulses aims at the creation of stroboscopic movies. Performing such experiments at one of the many recently established accelerator-based 4th-generation light sources such as free-electron lasers or superradiant THz sources allows an enormous widening of the accessible parameter space for the excitation and/or probing light pulses. Compared to table-top devices, critical issues of this type of experiment are fluctuations of the timing between the accelerator and external laser systems and intensity instabilities of the accelerator-based photon sources. Existing solutions have so far been only demonstrated at low repetition rates and/or achieved a limited dynamic range in comparison to table-top experiments, while the 4th generation of accelerator-based light sources is based on superconducting radio-frequency technology, which enables operation at MHz or even GHz repetition rates. In this article, we present the successful demonstration of ultra-fast accelerator-laser pump-probe experiments performed at an unprecedentedly high repetition rate in the few-hundred-kHz regime and with a currently achievable optimal time resolution of 13 fs (rms). Our scheme, based on the pulse-resolved detection of multiple beam parameters relevant for the experiment, allows us to achieve an excellent sensitivity in real-world ultra-fast experiments, as demonstrated for the example of THz-field-driven coherent spin precession. PMID:28382317

  20. Probing ultra-fast processes with high dynamic range at 4th-generation light sources: Arrival time and intensity binning at unprecedented repetition rates.

    PubMed

    Kovalev, S; Green, B; Golz, T; Maehrlein, S; Stojanovic, N; Fisher, A S; Kampfrath, T; Gensch, M

    2017-03-01

    Understanding dynamics on ultrafast timescales enables unique and new insights into important processes in the materials and life sciences. In this respect, the fundamental pump-probe approach based on ultra-short photon pulses aims at the creation of stroboscopic movies. Performing such experiments at one of the many recently established accelerator-based 4th-generation light sources such as free-electron lasers or superradiant THz sources allows an enormous widening of the accessible parameter space for the excitation and/or probing light pulses. Compared to table-top devices, critical issues of this type of experiment are fluctuations of the timing between the accelerator and external laser systems and intensity instabilities of the accelerator-based photon sources. Existing solutions have so far been only demonstrated at low repetition rates and/or achieved a limited dynamic range in comparison to table-top experiments, while the 4th generation of accelerator-based light sources is based on superconducting radio-frequency technology, which enables operation at MHz or even GHz repetition rates. In this article, we present the successful demonstration of ultra-fast accelerator-laser pump-probe experiments performed at an unprecedentedly high repetition rate in the few-hundred-kHz regime and with a currently achievable optimal time resolution of 13 fs (rms). Our scheme, based on the pulse-resolved detection of multiple beam parameters relevant for the experiment, allows us to achieve an excellent sensitivity in real-world ultra-fast experiments, as demonstrated for the example of THz-field-driven coherent spin precession.

  1. Ozone pretreatment of process waste water generated in course of fluoroquinolone production.

    PubMed

    Daoud, Fares; Pelzer, David; Zuehlke, Sebastian; Spiteller, Michael; Kayser, Oliver

    2017-10-01

    During production of active pharmaceutical ingredients, process waste water is generated at several stages of manufacturing. Whenever possible, the resulting waste water will be processed by conventional waste water treatment plants. Currently, incineration of the process waste water is the method to eliminate compounds with high biological activity. Thus, ozone treatment followed by biological waste water treatment was tested as an alternative method. Two prominent representatives of the large group of fluoroquinolone antibiotics (ciprofloxacin and moxifloxacin) were investigated, focussing on waste water of the bulk production. Elimination of the target compounds and generation of their main transformation products were determined by liquid chromatography - high resolution mass spectrometry (LC-HRMS). The obtained results demonstrated, that the concentration of moxifloxacin and its metabolites can be effectively reduced (>99.7%) prior entering the receiving water. On the contrary, the concentration of ciprofloxacin and its metabolites remained too high for safe discharge, necessitating application of prolonged ozonation for its further degradation. The required ozonation time can be estimated based on the determined kinetics. To assure a low biological activity the ecotoxicity of the ozonated waste water was investigated using three trophic levels. By means of multiple-stage mass spectrometry (MS(n)) experiments several new transformation products of the fluoroquinolones were identified. Thus, previously published proposed structures could be corrected or confirmed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Micromorphology of resin/dentin interfaces using 4th and 5th generation dual-curing adhesive/cement systems: a confocal laser scanning microscope analysis.

    PubMed

    Arrais, Cesar A G; Miyake, Katsuia; Rueggeberg, Frederick A; Pashley, David H; Giannini, Marcelo

    2009-02-01

    This study evaluated the differential composition of resin/dentin interfaces of indirect restorations created by the application of 4th and 5th generation dual-curing luting systems (bonding agents/resin cements), when each material was either light cured or allowed to self-cure. Occlusal flat dentin surfaces of 60 human third molars were assigned into 12 groups (n = 5) according to curing mode and dual-curing cementing system: 4th generation All Bond2 (AB2)/Duolink (Bisco) and 5th generation (B1) Bond1/Lute-it (Pentron). Fluorescein-labeled dextran (FDx) was mixed with the bonding agents, while rhodamine-labeled dextran (RhDx) was incorporated into resin cements and Pre-Bond resin from AB2. Resin cements were applied to 2-mm-thick, precured resin composite disks (Z250, 3M ESPE), which were fixed to dentin surfaces containing adhesive resin in either cured (light cured; LC) or uncured (self-cured; SC) states. The restored teeth were light activated (XL3000, 3M ESPE) according to the manufacturers' instructions (LRC) or allowed to self-cure (SRC), were stored for 24 h, and then vertically, serially sectioned into l-mm-thick slabs, which were analyzed using confocal laser scanning microscopy. Fluorescent additives indicated where individual components of the bonding/cement systems were located. Additional specimens were prepared and analyzed using a conventional scanning electron microscope. AB2/LC and B1/LC exhibited nonuniform primer/adhesive layer thickness. AB2/SC showed adhesive resin penetration within the primed dentin, and resin cement penetration at the entrance of the dentin tubules. B1/SC/LRC demonstrated resin cement penetration within the hybrid layer and into the dentin tubules. More resin cement penetration was observed in B1/SC/SRC groups than in its LRC equivalent. The morphological features and component interactions among materials at resin/dentin interfaces are related to the activation modes of the primer/adhesive layer and of the resin cement

  3. Second-generation surveillance for HIV/AIDS in Pakistan: results from the 4th round of Integrated Behavior and Biological Survey 2011–2012

    PubMed Central

    Emmanuel, Faran; Salim, Momina; Akhtar, Naeem; Arshad, Salwa; Reza, Tahira Ezra

    2013-01-01

    Objectives In an effort to fully analyse and understand the HIV situation and its epidemiology in Pakistan, a bilateral collaboration between the National AIDS Control Program and the Canadian International Development Agency resulted in the establishment of an effective second-generation surveillance (SGS) system for HIV/AIDS between 2004 and 2012 in accordance with the published guidelines. This paper presents findings from the 4th round of SGS. Methods A mapping exercise was initially conducted for size estimations of the key vulnerable populations: people who inject drugs (PWIDs), male sex workers (MSWs), hijra sex workers (HSWs), and female sex workers (FSWs), followed by an Integrated Behavioral and Biological Surveillance in 20 selected cities across Pakistan. Results The estimated sizes of the four key populations mapped in the 20 cities were 89 178 FSWs, 46 351 PWIDs, 23 317 HSWs and 19 119 MSWs. The HIV sero-prevalence among PWIDs was the highest among all key populations surveyed at 37.8% (CI 37.3 to 38.3) nationally, followed by a prevalence of 7.2% (CI 6.8 to 7.5) among HSWs, 3.1% (CI 2.8 to 3.4) among MSWs and 0.8% (CI 0.4 to 1.0) for FSWs. Various key risk behaviours, that is, sharing of syringes by PWIDs and inconsistent use of condoms by sex workers, were documented. Conclusions Pakistan's HIV epidemic that once was characterised primarily by transmission among PWIDs is now increasingly characterised by significant sexual transmission, and all types of sex workers (male, hijra and female) exhibit epidemiological proportions of infection. There is a need to develop concrete strategic plans for each vulnerable subpopulation, initially focusing prevention resources on those with a higher risk or vulnerability. PMID:23912818

  4. Fluoroquinolone and Third-Generation-Cephalosporin Resistance among Hospitalized Patients with Urinary Tract Infections Due to Escherichia coli: Do Rates Vary by Hospital Characteristics and Geographic Region?

    PubMed Central

    Bidell, Monique R.; Palchak, Melissa; Mohr, John

    2016-01-01

    This analysis of nearly 10,000 hospital-associated urinary tract infection (UTI) episodes due to Escherichia coli showed that fluoroquinolone and third-generation-cephalosporin resistance rates were 34.5% and 8.6%, respectively; the rate of concurrent resistance to both agents was 7.3%. Fluoroquinolone resistance rates exceeded 25% regardless of geographic location or hospital characteristics. The findings suggest that fluoroquinolones should be reserved and third-generation cephalosporins be used with caution as empirical agents for hospitalized patients with UTIs due to E. coli. PMID:26926640

  5. 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.

  6. Implementation of an intensified antibiotic stewardship programme targeting third-generation cephalosporin and fluoroquinolone use in an emergency medicine department.

    PubMed

    Borde, Johannes P; Kern, Winfried V; Hug, Martin; Steib-Bauert, Michaela; de With, Katja; Busch, Hans-Jörg; Kaier, Klaus

    2015-07-01

    Early initiation of antimicrobial treatment for acute infection is an important task in the emergency department (ED) with a likely impact on the hospital-wide antibiotic use pattern. We implemented an antibiotic stewardship (ABS) programme focused on non-trauma emergency patients at a large university hospital centre targeting broad-spectrum cephalosporin and fluoroquinolone use. Guidelines and focused discussion groups emphasised reduced prescription of third-generation cephalosporins and fluoroquinolones and encouraged penicillins. Antibiotic consumption expressed as monthly drug density in WHO-Anatomical Therapeutic Chemical defined and locally recommended daily doses (DDD and RDD) per 100 patient days was analysed before (January 2008 to October 2011) and after starting the intervention (January 2012 to October 2013). We performed a before-and-after uncontrolled interventional study using interrupted time-series (ITS) analysis in one ED to investigate ABS intervention-related effects in a quasiexperimental research setting. The mean monthly total antibiotic use density declined from 111 RDD (138 DDD) per 100 patient days before the intervention to 86 RDD (128 DDD) per 100 patient days after starting the intervention. Among the different antibacterial drug classes, the consumption of third-generation cephalosporins showed the largest reduction and dropped significantly by -68% between preintervention and postintervention periods. Using the RDD dataset, ITS confirmed a highly significant postintervention change in level of third-generation cephalosporins (-15.2, 95% CI (-24.08 to -6.311)) and a corresponding increase in the use of aminopenicillin/betalactamase inhibitor formulations (+6.6, 95% CI (4.169 to 9.069)). The drug use densities for fluoroquinolones and for overall antibiotics declined, however, the postinterventional level changes missed statistical significance--overall (95% CI (-39.99 to 0.466), fluoroquinolones 95% CI (-11.72 to 4.333)). An

  7. Topical ophthalmic fourth-generation fluoroquinolones: Appropriate use and cost considerations.

    PubMed

    Fiscella, Richard G; Lewis, Charles C; Jensen, Michael K

    2007-10-01

    The utilization and refill rates of topical ophthalmic fourth-generation fluoroquinolones among physicians, as well as the associated costs, were studied. A large data set of retrospective pharmacy prescription claims was obtained from multiple plans, including commercial managed care organizations, Medicaid, and Medicare. The data included the number and cost of all new and refill prescriptions for six months for gatifloxacin 0.3% and moxifloxacin 0.5% by physician specialty. New prescription and refill data were also analyzed from a state Medicaid plan to determine if similar trends existed. Primary care physicians wrote approximately 7,000 (7.7%) gatifloxacin and 84,000 (92.3%) moxifloxacin prescriptions, with pediatricians accounting for 4,000 (5.1%) gatifloxacin and 75,000 (94.9%) moxifloxacin prescriptions. Eye care physicians accounted for a similar amount of prescriptions for each antibiotic during the same period. The total cost of prescriptions for all primary care practitioners was approximately $170,000 for gatifloxacin and $2.5 million for moxifloxacin; prescriptions written by pediatricians accounted for $110,000 for gatifloxacin and $2.2 million for moxifloxacin. Prescription drug claims from payers using pharmacy benefit management companies during a six-month period indicated that the numbers of prescriptions written for gatifloxacin and moxifloxacin were similar among eye care physicians, but primary care physicians wrote a greater number of prescriptions for moxifloxacin. Analysis of claims to a Medicaid database revealed an increase in the prescriptions written by primary care physicians for moxifloxacin after its addition to the drug formulary.

  8. Endophthalmitis after uncomplicated cataract surgery with the use of fourth-generation fluoroquinolones: a retrospective observational case series.

    PubMed

    Moshirfar, Majid; Feiz, Vahid; Vitale, Albert T; Wegelin, Jacob A; Basavanthappa, Screenivasa; Wolsey, Darcey H

    2007-04-01

    To estimate the rate of acute postoperative endophthalmitis after uncomplicated cataract surgery in patients treated before and after surgery with 1 of 2 different fourth-generation fluoroquinolone ophthalmic drops for surgical prophylaxis. Retrospective, multicenter, observational case series. Included in this study were 20,013 patients from 9 cataract surgery centers in 7 states in the United States. Patients who had undergone uncomplicated phacoemulsification who received preoperative and postoperative topical fourth-generation fluoroquinolones for surgical prophylaxis between March 2003 and July 2005 were included in the study. The files of patients in whom acute endophthalmitis developed were reviewed and analyzed. Number and rate of endophthalmitis cases after uncomplicated cataract surgery. During the study period, the participating surgeons performed 20,013 uncomplicated surgeries. Of these, 16,209 patients (81%) received topical gatifloxacin and 3804 patients (19%) were treated with topical moxifloxacin as antiinfective prophylaxis. A total of 14 patients experienced endophthalmitis. The overall rate of endophthalmitis was 0.07%. There were 9 endophthalmitis patients in the gatifloxacin group and 5 endophthalmitis patients in the moxifloxacin group. The rate of endophthalmitis in the gatifloxacin group was 0.06% and the rate in the moxifloxacin group was 0.1%. The difference in the rate of endophthalmitis between the 2 groups was not statistically significant. In 10 of the patients, vitreous culture results were positive. Coagulase-negative staphylococci, followed by streptococci, species were the most commonly isolated organisms in the culture-positive patients. The overall rate of endophthalmitis after uncomplicated cataract surgery in patients treated with topical fourth-generation fluoroquinolones as antiinfective prophylaxis was 0.07%. This rate was within the range of previously reported rates of endophthalmitis in the literature. The difference in

  9. 4th Annual IRIS Workshop Held

    NASA Astrophysics Data System (ADS)

    Wiens, Douglas

    About 200 scientists gathered at the 4th annual Incorporated Research Institutions for Seismology (IRIS) workshop in Santa Fe, N. Mex., April 12-14 and discussed recent research results obtained with the new generation of seismological instruments. The meeting provided a forum for developing new initiatives and disseminating information on how to access the IRIS Data Management Center. Organizers of the scientific program were Douglas Wiens of Washington University in St. Louis and Terry Wallace of the University of Arizona.

  10. Review of third-and fourth-generation fluoroquinolones in ophthalmology: in-vitro and in-vivo efficacy.

    PubMed

    Scoper, Stephen V

    2008-10-01

    Beginning with second-generation ciprofloxacin 0.3% and ofloxacin 0.3%, fluoroquinolones have been widely used in the treatment and prophylaxis of ocular infections. However, their in-vitro potencies have been decreasing steadily since their introduction. Third-generation levofloxacin 0.5% produces higher ocular tissue penetration, thereby reducing the risk of selecting for decreased fluoroquinolone potency. Fourth-generation gatifloxacin 0.3% and moxifloxacin 0.5% have structural modifications that both reduce risk of resistance and improve potency against Gram-positive bacteria. A new third-generation formulation, levofloxacin 1.5%, was recently introduced, demonstrating increased ocular penetration compared with gatifloxacin 0.3% but clinical equivalence to its second-generation parent, ofloxacin 0.3%, in two randomized trials. We investigated the therapeutic potential of levofloxacin 1.5% and compared it to that of existing fourth-generation fluoroquinolones. A MEDLINE search was conducted using the following search terms: moxifloxacin or gatifloxacin; levofloxacin; minimum inhibitory concentration or prevention or prophylaxis; keratitis or endophthalmitis. Nine eligible studies published between 2002 and 2008 were identified, eight of which are presented. The five in-vitro studies demonstrated that moxifloxacin and gatifloxacin are statistically more potent than levofloxacin against Gram-positive organisms and similar in potency in most cases of Gram-negative bacteria. In-vivo animal models testing moxifloxacin or gatifloxacin against levofloxacin 0.5% (no clinical trials testing the efficacy of levofloxacin 1.5% have yet been published) demonstrated that fourth-generation agents were superior to third-generation levofloxacin 0.5% for prophylaxis of Gram-positive bacteria-induced infections and were equal to, or better than, levofloxacin 0.5% for the treatment of Gram-negative infections. Fourth-generation agents have increased potency against Gram

  11. Effects of fluoroquinolone eye solutions without preservatives on human corneal epithelial cells in vitro.

    PubMed

    Oum, Boo Sup; Kim, Na Mi; Lee, Jong Soo; Park, Young Min

    2014-01-01

    To evaluate the biologic effects of fluoroquinolone eye solutions without preservatives on cultured human corneal epithelial cells in vitro. We studied the effect of diverse generations of topical fluoroquinolones such as ofloxacin 0.3%, levofloxacin 0.5%, tosufloxacin 0.3%, moxifloxacin 0.5% and gatifloxacin 0.3% on cultured human corneal epithelial cells. MTT-based calorimetric assay, lactate dehydrogenase leakage (LDH) assay and scratch wound test were performed. Corneal epithelial cell morphologies were examined by performing inverted light microscopy and transmission electron microscopy. In all topical fluoroquinolones, the metabolic activity of the corneal epithelial cells decreased in a time-dependent fashion and the LDH titer increased with longer exposure times. Especially, the LDH titers significantly increased after exposure to moxifloxacin 0.5% and gatifloxacin 0.3% compared with controls. The migration rates of the corneal epithelial cells were faster in ofloxacin 0.3% or levofloxacin 0.5% than other fluoroquinolones. Severe cellular morphological damage was observed after exposure to moxifloxacin 0.5% and gatifloxacin 0.3%. As moxifloxacin 0.5% and gatifloxacin 0.3% induced the toxic effect to the corneal epithelial cells, compared with other fluoroquinolones, the 4th fluoroquinolone eye solutions should be carefully used in case of the corneal epithelium is damaged by long duration of treatment or overdosage. © 2014 S. Karger AG, Basel.

  12. 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.

  13. [Treatment of drug resistant destructive pulmonary tuberculosis: gemifloxacin and other fluoroquinolones clinical efficiency and tolerance at the end of initial phase of treatment].

    PubMed

    Petrenko, V I; Radysh, H V

    2013-12-01

    Gemifloxacin efficiency and tolerance in comparison to the ofloxacin, levofloxacin and gatifloxacin during the intensive phase of the antituberculosis therapy for drug resistant cases was evaluated. 156 drug resistant TB patients were examined in the open, prospective, randomized research, being divided into 2 groups with similar drug resistance profile. The 1st group received gemifloxacin, the 2nd--other fluoroquinolones. Gemifloxacin efficiency in the treatment regimen for the drug resistant TB patients did not differ from the efficiency of the use of other fluoroquinolones of the 4th generation and was significantly higher in comparison to ofloxacin. At the same time the identical level of side effects was registered in the course of treatment with mentioned drugs. Gemifloxacin is effective and safe at treatment of tuberculosis in comparison to other fluoroquinolones that allows considering it as the drug of choice among fluoroquinolones for treatment of drug resistant TB, including multidrug-resistant TB.

  14. Multi-centre field evaluation of the performance of the Trinity Biotech Uni-Gold HIV 1/2 rapid test as a first-line screening assay for gay and bisexual men compared with 4th generation laboratory immunoassays.

    PubMed

    Keen, P; Conway, D P; Cunningham, P; McNulty, A; Couldwell, D L; Davies, S C; Smith, D E; Gray, J; Holt, M; O'Connor, C C; Read, P; Callander, D; Prestage, G; Guy, R

    2017-01-01

    The Trinity Biotech Uni-Gold HIV test (Uni-Gold) is often used as a supplementary rapid test in testing algorithms. To evaluate the operational performance of the Uni-Gold as a first-line screening test among gay and bisexual men (GBM) in a setting where 4th generation HIV laboratory assays are routinely used. We compared the performance of Uni-Gold with conventional HIV serology conducted in parallel among GBM attending 22 testing sites. Sensitivity was calculated separately for acute and established infection, defined using 4th generation screening Ag/Ab immunoassay (EIA) and Western blot results. Previous HIV testing history and results of supplementary 3rd generation HIV Ab EIA, and p24 antigen EIA were used to further characterise cases of acute infection. Of 10,793 specimens tested with Uni-Gold and conventional serology, 94 (0.90%, 95%CI:0.70-1.07) were confirmed as HIV-positive by conventional serology, and 37 (39.4%) were classified as acute infection. Uni-Gold sensitivity was 81.9% overall (77/94, 95%CI:72.6-89.1); 56.8% for acute infection (21/37, 95%CI:39.5-72.9) and 98.2% for established infection (56/57, 95%CI:90.6-100.0). Of 17 false non-reactive Uni-Gold results, 16 were acute infections, and of these seven were p24 antigen reactive but antibody negative. Uni-Gold specificity was 99.9% (10,692/10,699, 95%CI:99.9-100.0), PPV was 91.7% (95%CI:83.6-96.6) and NPV was 99.8% (95%CI:99.7-99.9), respectively. In this population, Uni-Gold had good specificity and sensitivity was high for established infections when compared to 4th generation laboratory assays, however sensitivity was lower in acute infections. Where rapid tests are used in populations with a high proportion of acute infections, additional testing strategies are needed to detect acute infections. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Bunch by bunch beam monitoring in 3rd and 4th generation light sources by means of single crystal diamond detectors and quantum well devices

    NASA Astrophysics Data System (ADS)

    Antonelli, M.; Di Fraia, M.; Tallaire, A.; Achard, J.; Carrato, S.; Menk, R. H.; Cautero, G.; Giuressi, D.; Jark, W. H.; Biasiol, G.; Ganbold, T.; Oliver, K.; Callegari, C.; Coreno, M.; De Sio, A.; Pace, E.

    2012-10-01

    New generation Synchrotron Radiation (SR) sources and Free Electron Lasers (FEL) require novel concepts of beam diagnostics to keep photon beams under surveillance, asking for simultaneous position and intensity monitoring. To deal with high power load and short time pulses provided by these sources, novel materials and methods are needed for the next generation BPMs. Diamond is a promising material for the production of semitransparent in situ X-ray BPMs withstanding the high dose rates of SR rings and high energy FELs. We report on the development of freestanding, single crystal CVD diamond detectors. Performances in both low and radio frequency SR beam monitoring are presented. For the former, sensitivity deviation was found to be approximately 2%; a 0.05% relative precision in the intensity measurements and a 0.1-μm precision in the position encoding have been estimated. For the latter, single-shot characterizations revealed sub-nanosecond rise-times and spatial precisions below 6 μm, which allowed bunch-by-bunch monitoring in multi-bunch operation. Preliminary measurements at the Fermi FEL have been performed with this detector, extracting quantitative intensity and position information for FEL pulses (~ 100 fs, energy 12 ÷ 60 eV), with a long-term spatial precision of about 85 μm results on FEL radiation damages are also reported. Due to their direct, low-energy band gap, InGaAs quantum well devices too may be used as fast detectors for photons ranging from visible to X-ray. Results are reported which show the capability of a novel InGaAs/InAlAs device to detect intensity and position of 100-fs-wide laser pulses.

  16. Clinical validation of a novel diagnostic HIV-2 total nucleic acid qualitative assay using the Abbott m2000 platform: Implications for complementary HIV-2 nucleic acid testing for the CDC 4th generation HIV diagnostic testing algorithm.

    PubMed

    Chang, Ming; Wong, Audrey J S; Raugi, Dana N; Smith, Robert A; Seilie, Annette M; Ortega, Jose P; Bogusz, Kyle M; Sall, Fatima; Ba, Selly; Seydi, Moussa; Gottlieb, Geoffrey S; Coombs, Robert W

    2017-01-01

    The 2014 CDC 4th generation HIV screening algorithm includes an orthogonal immunoassay to confirm and discriminate HIV-1 and HIV-2 antibodies. Additional nucleic acid testing (NAT) is recommended to resolve indeterminate or undifferentiated HIV seroreactivity. HIV-2 NAT requires a second-line assay to detect HIV-2 total nucleic acid (TNA) in patients' blood cells, as a third of untreated patients have undetectable plasma HIV-2 RNA. To validate a qualitative HIV-2 TNA assay using peripheral blood mononuclear cells (PBMC) from HIV-2-infected Senegalese study participants. We evaluated the assay precision, sensitivity, specificity, and diagnostic performance of an HIV-2 TNA assay. Matched plasma and PBMC samples were collected from 25 HIV-1, 30 HIV-2, 8 HIV-1/-2 dual-seropositive and 25 HIV seronegative individuals. Diagnostic performance was evaluated by comparing the outcome of the TNA assay to the results obtained by the 4th generation HIV screening and confirmatory immunoassays. All PBMC from 30 HIV-2 seropositive participants tested positive for HIV-2 TNA including 23 patients with undetectable plasma RNA. Of the 30 matched plasma specimens, one was HIV non-reactive. Samples from 50 non-HIV-2 infected individuals were confirmed as non-reactive for HIV-2 Ab and negative for HIV-2 TNA. The agreement between HIV-2 TNA and the combined immunoassay results was 98.8% (79/80). Furthermore, HIV-2 TNA was detected in 7 of 8 PBMC specimens from HIV-1/HIV-2 dual-seropositive participants. Our TNA assay detected HIV-2 DNA/RNA in PBMC from serologically HIV-2 reactive, HIV indeterminate or HIV undifferentiated individuals with undetectable plasma RNA, and is suitable for confirming HIV-2 infection in the HIV testing algorithm. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Topical ocular delivery of fluoroquinolones.

    PubMed

    Pawar, Pravin; Katara, Rajesh; Mishra, Sushil; Majumdar, Dipak K

    2013-05-01

    Topical fluoroquinolones are used in ophthalmology to treat ocular infections. They are bactericidal and inhibit bacterial DNA replication by inhibiting DNA gyrase and topoisomerase. Fluoroquinolones possess two ionizable groups: a carboxylic group (pKa1 = 5.5 - 6.34) and a heterocyclic group (pKa2 = 7.6 - 9.3), in the nucleus, which acquire charge at pH above and below the isoelectric point (pI = 6.75 - 7.78). At isoelectric point, fluoroquinolones remain unionized and show enhanced corneal penetration but exhibit reduced aqueous solubility and the drug may precipitate from aqueous solution. Aqueous ophthalmic solutions of fluoroquinolones are obtained by using hydrochloride or mesylate salt which is acidic and irritating to the eyes. Hence, pH of the solution is kept between 5 and 7 to ensure aqueous solubility and minimum ocular irritation. This review gives an overview of various physicochemical and formulation factors affecting the ocular delivery of fluoroquinolones and strategies for getting higher ocular bioavailability for ocular delivery of fluoroquinolones. These strategies could be employed to improve efficacy of fluoroquinolones in eye preparation. Broad-spectrum antibacterials, such as the ophthalmic fluoroquinolones, are powerful weapons for treating and preventing potentially sight-threatening infections. The fourth-generation fluoroquinolones have quickly assumed an outstanding place in the ophthalmic applications. Especially valuable for their broad-spectrum coverage against Gram-positive and Gram-negative organisms, these agents have become the anti-infective of preference for many ophthalmologists. Moxifloxacin seems to be a promising powerful molecule among all fluoroquinolones for treatment of bacterial infections.

  18. [Fluoroquinolones in children].

    PubMed

    Gendrel, D

    2002-01-01

    The only currently recommended pediatric use of fluoroquinolones involves ciprofloxacine for treatment of pyocyanic infection in children with cystic fibrosis. The main contraindication for use of fluoroquinolones in children is arthrotoxicity. Notwithstanding they are occasionally used for serious infections when there is no other therapeutic alternative. In addition to cystic fibrosis, potential pediatric indications include multidrug-resistant salmonella and shigellosis, certain enterobacterial infections in newborns, complicated urinary tract infections, and severe multidrug-resistant bacterial infection especially in immunocompromised subjects. The availability of new quinolones against pneumococcus should have little impact on current therapeutic strategies for upper or lower respiratory tract infections since potential indications in children are limited. However when the new generation reaches the market, fluoroquinolones should offer new alternatives for treatment of penicillin-resistant pneumococcal meningitis. Studies comparing children and adults have shown that arthrotoxicity is approximately the same or only slightly higher. The main problem for assessment of adverse effects is that pediatricians often fail to report the limited number of cases in which fluoroquinoles have been prescribed. Regardless fluoroquinolones must remain a second or third line agent for treatment of severe infection in cases in which no other alternative especially by the oral route is available. Use must be restricted to situations in which the risks are outweighed by potential benefits. Limiting pediatric use will slow down the emergence of resistant bacteria.

  19. Outlines of an "exploding" network of metabolites generated from the fluoroquinolone enrofloxacin by the brown rot fungus Gloeophyllum striatum.

    PubMed

    Karl, W; Schneider, J; Wetzstein, H-G

    2006-06-01

    Degradation of the veterinary fluoroquinolone antibiotic enrofloxacin (EFL) was studied with three strains of Gloeophyllum, basidiomycetous fungi thought to produce extracellular hydroxyl radicals. Metabolites generated in a mineral medium were analyzed by combined high-performance liquid chromatography/high-resolution electrospray ionization mass spectrometry. Their origin was inferred from peak doublets representing 12C and 14C isotopomers detected at a defined proportion. From each exact molecular mass, the molecular formula was derived for which the most probable chemical structure was postulated, using for guidance 18 known EFL metabolites. All supernatants provided similar metabolite patterns, with the most comprehensive consisting of 87 compounds. These metabolites belonged to five families headed by EFL, its oxidatively decarboxylated or defluorinated congeners, an isatin-, and an anthranilic acid-type derivative. Metabolites hydroxylated in the aromatic part suggested the formation of three catechols and two oxidizable ortho-aminophenol-type compounds. After oxidation to the respective ortho-quinones or ortho-quinone imines and oxidative ring cleavage at one of three alternative sites, the formation of various cis,cis-muconic acid-type derivatives is likely, one of which could be detected. Anthranilic acid-type compounds provided two additional sites for ortho-aminophenol formation and aromatic ring cleavage. An "exploding" network of diverse EFL congeners produced by Gloeophyllum suggests the broad utility of our model for studying biodegradation.

  20. 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…

  1. 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…

  2. Community-acquired pneumonia: impact of empirical antibiotic therapy without respiratory fluoroquinolones nor third-generation cephalosporins.

    PubMed

    Pradelli, J; Risso, K; de Salvador, F G; Cua, E; Ruimy, R; Roger, P-M

    2015-03-01

    Guidelines for inpatients with community-acquired pneumonia (CAP) propose to use respiratory fluoroquinolone (RFQ) and/or third-generation cephalosporins (Ceph-3). However, broad-spectrum antibiotic therapy is associated with the emergence of drug-resistant bacteria. We established a guideline in which RFQ and Ceph-3 were excluded as a first course. Our aim was to evaluate the impact of our therapeutic choices for CAP on the length of hospital stay (LOS) and patient outcome. This was a cohort study of patients with CAP from July 2005 to June 2014. We compared patients benefiting from our guideline established in 2008 to those receiving non-consensual antibiotics. Disease severity was evaluated through the Pneumonia Severity Index (PSI). The empirical treatment for PSI III to V was a combination therapy of amoxicillin-clavulanic acid (AMX-C) + roxithromycin (RX) or AMX + ofloxacin. Adherence to guidelines was defined by the prescription of one of these antibiotic agents. Requirement for intensive care or death defined unfavorable outcome. Among 1,370 patients, 847 were treated according to our guideline (61.8 %, group 1) and 523 without concordant therapy (38.2 %, group 2). The mean PSI was similar: 82 vs. 83, p > 0.5. The mean LOS was lower in group 1: 7.6 days vs. 9.1 days, p < 0.001. An unfavorable outcome was less frequent in group 1: 5.4 % vs. 9.9 %, p = 0.001. In logistic regression models, concordant therapy was associated with a favorable outcome: adjusted odds ratio (AOR) [95 % confidence interval (CI)] 1.85 [1.20-2.88], p = 0.005. CAP therapy without RFQ and Ceph-3 use was associated with a shorter LOS and fewer unfavorable outcomes.

  3. 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

  4. Peer Review Handbook 4th Edition, 2015

    EPA Pesticide Factsheets

    The 4th edition of EPA's Peer Review Handbook, 2015 is the most up to date version. It was prepared for the U.S. Environmental Protection Agency by Members of the Peer Review Advisory Group under the direction of EPA’s Science and Technology Policy Council

  5. 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…

  6. [Fluoroquinolones: Non-antibacterial properties].

    PubMed

    Leyva-Ramos, S; Hernández-López, H

    2017-02-01

    Fluoroquinolones are a class of well-established chemotherapeutic agents with a potent biological activity being the structure of 4-quinolone-3-carboxilic acids privileged because it contains different sites for functionalization allowing expand its use in clinical practice for their antifungal, antiviral and anticancer activities. Quinolones structural changes have resulted in a first, second, third and fourth generation of drugs so it is advisable to continue modifying existing structures in new ways to generate compounds with desirable biological and pharmacological properties.

  7. Fluoroquinolone resistance in Campylobacter

    USDA-ARS?s Scientific Manuscript database

    Fluoroquinolone-resistant Campylobacter jejuni and C. coli are common in animals because of the use of fluoroquinolones as therapeutic agents in animal husbandry, particularly in chickens and other poultry. Campylobacter is a commensal in poultry, and therefore, poultry and poultry products are the...

  8. Safety concerns with fluoroquinolones.

    PubMed

    Mehlhorn, Allana J; Brown, Dana A

    2007-11-01

    To review the chemistry, pharmacology, and safety of fluoroquinolones. A MEDLINE search (1966-July 2007) was conducted using the key words fluoroquinolones or quinolones with safety, adverse effects, hypoglycemia, hyperglycemia, dysglycemia, QTc prolongation, torsades, seizures, phototoxicity, tendon rupture, Clostridium difficile, and pseudomembranous colitis for articles published in the English language. Medicinal chemistry, in vitro, animal, and human trials were reviewed for information on the chemistry, pharmacology, and safety of each fluoroquinolone. Clinical trials were reviewed and included to compare the safety of systemic fluoroquinolones on the market. Literature on the pathology of serious adverse effects was also reviewed. Gatifloxacin has been shown to increase the risk of hospitalization for dysglycemia in patients with and without diabetes. Hyperglycemia may occur with any fluoroquinolone, especially if not properly dose adjusted. Hypoglycemia may occur with any fluoroquinolone and has a higher frequency in patients receiving concomitant oral hypoglycemic drugs or insulin. Use of any fluoroquinolone should be avoided in patients with risk factors for QTc interval prolongation or tendinopathy. All fluoroquinolones should be used with caution in patients with a history of seizure disorders and may cause phototoxicity or C. difficile-associated diarrhea (CDAD). Clinicians should be aware of possible alterations in blood glucose, QTc interval prolongation, seizures, phototoxicity, tendinopathy, or CDAD with the use of any fluoroquinolone, especially in patients with other risk factors for these conditions. Clinicians should closely monitor for these adverse effects and appropriately adjust doses to minimize these risks. To provide safe treatment for patients needing antibiotic therapy, an assessment of the risk-benefit ratio may be warranted in the decision to use a fluoroquinolone.

  9. 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

  10. 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.

  11. Promoting Maternal and Infant Health in the 4th Trimester

    ERIC Educational Resources Information Center

    Verbiest, Sarah B.; Tully, Kristin P.; Stuebe, Alison M.

    2017-01-01

    The "4th trimester" refers to the transition period after childbirth when infants are adjusting to life outside the womb and mothers are adjusting to new parenthood. This critical period is marked by significant biological, psychological, and social changes, which are currently insufficiently supported. The 4th trimester perspective…

  12. Fluoroquinolone resistance in campylobacter.

    PubMed

    Smith, James L; Fratamico, Pina M

    2010-06-01

    Campylobacter is a commensal in poultry, and therefore, poultry and poultry products are major sources of Campylobacter infections in humans. Fluoroquinolones inhibit the growth of Campylobacter and other microorganisms by binding to bacterial DNA gyrase and DNA topoisomerase IV. These enzymes are associated with bacterial transcription, replication, and chromosome condensation and segregation. Selection pressure in the presence of fluoroquinolones rapidly leads to resistance in Campylobacter, due to the selection for mutations in DNA gyrase. Fluoroquinolone-resistant campylobacters have been found in poultry feces and carcasses, and in retail poultry meat products in most areas of the world. In addition, other food animals and the meat products from those animals have been shown contaminated with fluoroquinolone-resistant campylobacters. Even the removal of fluoroquinolones from use in treating animal diseases has not entirely eliminated the presence of resistant Campylobacter jejuni and Campylobacter coli from animals and animal products. Human exposure to Campylobacter infection could be reduced by using strategies that decrease colonization of chickens by the pathogen.

  13. Venezuela as an Exporter of 4th Generation Warfare Instability

    DTIC Science & Technology

    2012-12-01

    psychological-economic-social factors that are most relevant in a targeted culture . But, like all oth- ers, this kind of conflict is intended to resist...this kind is political-military, economic-commercial, or cultural - moral. Within the context of these combinations, there is a difference between...Narco-criminal war/financial war/psychologi- cal/media war (e.g., Mexico , to date); • Guerrilla war/psychological-media war/nar- co-criminal war

  14. Low prevalence of fluoroquinolone resistant strains and resistance precursor strains in Streptococcus pneumoniae from patients with community-acquired pneumonia despite high fluoroquinolone usage.

    PubMed

    Pletz, Mathias W; van der Linden, Mark; von Baum, Heike; Duesberg, Christoph B; Klugman, Keith P; Welte, Tobias

    2011-01-01

    We investigated the usage of fluoroquinolones and the prevalence of fluoroquinolone resistant pneumococci and their precursors (first step mutants and efflux expressing isolates) in patients with community-acquired pneumonia, who were enroled into the German CAPNETZ surveillance study from 2002 to 2006 before the introduction of the pneumococcal conjugate vaccine (n=5780). Thirty-eight percent of all outpatients received fluoroquinolones. Moxifloxacin accounted for 70%, levofloxacin for 19% and ciprofloxacin for 9% of all fluoroquinolone prescriptions. One hundred and sixty-three pneumococcal isolates from 556 patients with pneumococcal pneumonia were analyzed for fluoroquinolone resistance, efflux phenotype, prevalence of mutations within the quinolone-resistance determining regions and clonality. None of the isolates exhibited fluoroquinolone resistance, 1.2% of the isolates contained a first step mutation and 6.7% exhibited an efflux phenotype. There was no clonal relationship among these strains at increased risk for fluoroquinolone resistance. The absence of fluoroquinolone resistance in the context of high fluoroquinolone usage might be explained by the high proportion of third-generation fluoroquinolones with enhanced activity against pneumococci. Copyright © 2010 Elsevier GmbH. All rights reserved.

  15. [Third and fourth generation fluoroquinolones].

    PubMed

    Rossi, C; Sternon, J

    2001-10-01

    Levofloxacin, levorotatory isomer of ofloxacine, is the only FQ3G on the belgian market since the middle of 2000 and is a little more efficient than the FQ2G against S. pneumoniae. The FQ4G are in vitro active against the common and atypic respiratory pathogenes and significantly more efficient against the Gram positive cocci, principally against S. pneumoniae. Their long duration of action allows one oral administration a day sufficient to obtain bactericidal levels in the serum. Their secondary effects are located principally at the level of digestive tract, neurologic system or cutaneous area. In the U.S.A., several FQ4G (clina-, grepa-, spar-, trova-floxacin) were withdrawn from use after observance of severe toxicity, while there were being administrated on a large scale. Furthermore, two of these "respiratory" FQ4G (gemi- and moxi-floxacin) should reinforced our therapeutic armoury, moxifloxacin as of 2002 and gemifloxacin as of 2004. The position of FQ3G and 4G are in discussion. In the case of pneumonia acquired in the community and confirmed by X-Ray, our recommendation is to administer a new FQ at the first choice if the patient is allergic to penicillin, debilitated or if a penicillin resistant S. pneumoniae suspected (epidemiology, recent antibiotherapy) and at the second choice if it is resistance to penicillin or to macrolide, in case of atypic pneumonia. Today, the majority of the pneumonia acquired outside the hospital is empirically treated with a betalactam (oral or intravenous), with or without macrolide. The new FQ are important drugs. One must avoid overprescription which leads to bacterial resistance (especially S. pneumoniae).

  16. Health Physics and Radiological Health, 4th Edition.

    PubMed

    Pfeiffer, Douglas

    2013-11-01

    Health Physics and Radiological Health, 4th Edition. Johnson Thomas E., Birky Brian K., Lippincott Williams & Wilkins, a Walter Kluwer business, Baltimore, Maryland, 2012, $205.99. ISBN: 9781609134198, 1288 pp. (hardcover). © 2013 American Association of Physicists in Medicine.

  17. Safety profile of the fluoroquinolones: focus on levofloxacin.

    PubMed

    Liu, Hans H

    2010-05-01

    The fluoroquinolone class of antibacterial agents are among the most frequently prescribed drugs, with utility in a broad range of bacterial infections. Although very useful agents, the fluoroquinolones as a class are associated with a number of adverse events, some with considerable clinical significance. In the past 15-20 years, tolerability concerns have led to restrictions on the use of the fluoroquinolones and, in some instances, the withdrawal of agents from the market. This review focuses on the safety and tolerability of levofloxacin, a third-generation fluoroquinolone, relative to other fluoroquinolones. A literature search was performed of the MEDLINE database encompassing the dates 1980-2009, using as keywords the drug names levofloxacin and concurrently marketed fluoroquinolones combined with the words 'safety', 'adverse effect' or 'adverse drug reaction', or the name of the specific adverse effect. Adverse events commonly associated with the fluoroquinolones include gastrointestinal and CNS toxicity (most frequently headache and dizziness), as well as other adverse events including ECG abnormalities (for example QT interval prolongation), disrupted glucose metabolism, phototoxicity, tendon and joint disorders, hypersensitivity and skin disorders, and hepatic toxicity. Package inserts for the fluoroquinolones in Europe and the US contain warnings regarding these risks. US package inserts also carry 'black-box' warnings regarding the risk of tendon rupture and joint disorders with these agents; however, there is a substantial body of evidence to indicate that there are marked differences in the tolerability profiles of the individual agents within the fluoroquinolone class. These differences may be explained, at least in part, by structural differences: all fluoroquinolones share a basic quinolone core, with differences in specific side chains underlying the adverse event relationships. Furthermore, many of the fluoroquinolone-associated adverse effects

  18. 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".

  19. 4(th) HUPO Brain Proteome Project Workshop in Munich, Germany.

    PubMed

    Hamacher, Michael; Stephan, Christian; Palacios Bustamante, Nadine; van Hall, Andre; Marcus, Katrin; Meyer, Helmut E

    2006-01-01

    More than 70 interested colleagues attended the 4(th) Workshop of HUPO's Brain Proteome Project. The project was presented within nine talks mainly focusing on two running pilot studies as well as on data re-processing. A bioinformatics jamboree in Hinxton, UK, and the 5th Workshop taking place in Dublin next February were announced.

  20. Improving 4th Grade Primary School Students' Reading Comprehension Skills

    ERIC Educational Resources Information Center

    Bulut, Aydin

    2017-01-01

    The aim of this study was to carry out action research to investigate reading comprehension skills when using the SQ3R reading comprehension strategy. To that end, this strategy was used for improving the reading comprehension skills of 7 primary school 4th grade students who had problems with these skills. An action plan was prepared for 3hours a…

  1. Fluoroquinolone toxicities. An update.

    PubMed

    Lietman, P S

    1995-01-01

    The main types of adverse effects associated with quinolones are uncommon and reversible and vary in frequency among different agents. Phototoxicity appears more frequent with lomefloxacin than with some other quinolones. Three mechanisms have been proposed to explain the neurotoxic effects, including rare proconvulsant activity, associated with quinolone therapy. Arthropathy remains a dilemma for paediatricians deciding whether to use quinolones in growing children. Importantly, the experience with temafloxacin, which has now been withdrawn from the market, emphasises the need for thorough postmarketing surveillance. Nonetheless, it should be remembered that the fluoroquinolones as a group are effective and very well tolerated antimicrobial drugs.

  2. 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

  3. ACSPRI 2014 4th International Social Science Methodology Conference Report

    DTIC Science & Technology

    2015-04-01

    and to present best practice standards and innovation within a range of disciplines. A member of the Technology Forecasting and Futures (TFF...interest to the Technology Forecasting and Futures (TFF) Group of JOAD presented at the ACSPRI 4th International Social Science Methodology conference...the dynamics of manual vs automated data analysis. Research findings related to these themes are contextualised for the TFF S&T forecasting

  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. Summary of the 4th Nordic Symposium on Digital Pathology

    PubMed Central

    Lundström, Claes; Waltersson, Marie; Persson, Anders; Treanor, Darren

    2017-01-01

    The Nordic symposium on digital pathology (NDP) was created to promote knowledge exchange across stakeholders in health care, industry, and academia. In 2016, the 4th NDP installment took place in Linköping, Sweden, promoting development and collaboration in digital pathology for the benefit of routine care advances. This article summarizes the symposium, gathering 170 attendees from 13 countries. This summary also contains results from a survey on integrated diagnostics aspects, in particular radiology-pathology collaboration. PMID:28382222

  6. Hypersensitivity reactions to fluoroquinolones.

    PubMed

    Scherer, Kathrin; Bircher, Andreas J

    2005-01-01

    Fluoroquinolone antibiotics cause immediate and delayed hypersensitivity reactions, and may also affect internal organs and circulating blood cells. The underlying pathomechanisms are only partly understood. The extent of cross-reactivity among different quinolones depends on the type of clinical manifestation and its underlying mechanism. Despite recent advances, reliable diagnostic tests are still lacking. Recent studies have shown quinolone-specific IgE in vitro in more than 50% of patients with immediate-type reactions and a considerable cross-reactivity with related compounds. In maculopapular drug exanthems from ciprofloxacin, specific T-cell clones were identified, and cross-reactivity to related compounds was detected in approximately 50% of the clones. From re-exposure studies in patients with exanthems, cross-reactivity appears to be lower. Cellular tests such as lymphocyte transformation tests are currently not very useful. For prick and intradermal skin tests, widely divergent nonirritant test concentrations have been recommended. Desensitization may be possible in selected patients.

  7. Report of the 4th European Zebrafish Principal Investigator Meeting.

    PubMed

    Lopes, Susana S; Distel, Martin; Linker, Claudia; Fior, Rita; Monteiro, Rui; Bianco, Isaac H; Portugues, Ruben; Strähle, Uwe; Saúde, Leonor

    2016-12-01

    The European Zebrafish Principal Investigator Meeting (EZPM) is an ideal forum for group leaders using this fantastic animal model not only to discuss science but also to strengthen their interactions, to push forward technological advances, and to define guidelines for the use of this fish in research. The city of Lisbon (Portugal) was voted by the European group leaders to be the setting for the 4th EZPM, and the organizing committee, composed by Leonor Saúde (iMM Lisboa, PT), Susana Lopes (CEDOC, PT), Michael Orger (Champalimaud Foundation, PT), Rui Oliveira (ISPA, PT), and António Jacinto (CEDOC, PT), was very enthusiastic to organize a productive event. The 4th EZPM took place from March 15 to 19 at Pavilhão do Conhecimento, a Science Museum and Educational Center winner of The Great Prize FAD of Arquitecture 1999 and The Society for Environmental Graphic Design Award 2011. Over 5 days, 135 group leaders (89 men and 46 women) coming from 19 different European countries and also from the United States, Turkey, Israel, Chile, and Singapore presented and discussed their recent research achievements. In addition to the scientific oral and poster presentations, the group leaders gathered in very lively community sessions on morphants versus mutants (chaired by Didier Stainier, Max Planck Institute for Heart and Lung Research, DE), funding issues (chaired by Uwe Strahle, KIT-ITG, DE), and gender equality (chaired by Corinne Houart, KCL, United Kingdom). One of the highlights of the 4th EZPM was the guided visit to Oceanário de Lisboa, an international award-winning place that celebrates life with a stunning display of living aquatic creatures.

  8. Fine PM2.5 around July 4th

    EPA Pesticide Factsheets

    Data used in these analyses was obtained from publically-available sources, specifically the EPA's AirNow website (https://www.epa.gov/outdoor-air-quality-data). The dataset provided includes the subset of data from AirNow that was used in our analyses.This dataset is associated with the following publication:Dickerson, A., A. Benson, B. Buckley, and E. Chan. Concentrations of individual fine particulate matter components in the United States around July 4th. Air Quality, Atmosphere & Health. Springer Netherlands, NETHERLANDS, 1-10, (2016).

  9. 4TH Marine Division Operation Plan Number 49-44

    DTIC Science & Technology

    1944-12-26

    I / i i -4- A. o. o o o 3 4-’ 4TH MARINE DIVISION 54 OPERATION PLAN NO. 49-44 DECLASSIFIED IAW CLIASSIFICATION $4...INTO ENEMY HANDS. LUISrAR! UNCLASS0FIDo .-O UNCLASSIFIED ri LL!n .. I . 155 - - o.- sr Report Documentation Page Form ApprovedOMB No. 0704-0188 Public...the remainder of O-1 within Z, repared or further OPN PLAN 49-44 - 1 - O1 :?’:¢ . ... ~·~:~ I I - I --" , I %,"_’,: A I 1-W_ , - I I ---. -

  10. Rate of Missing Socioeconomic Factors in the 4th KNHANES.

    PubMed

    Park, Hyun Ah

    2012-11-01

    This study is to assess how missing values in socioeconomic status (SES) variables were handled in the Korean Journal of Family Medicine (KJFM) article using the Korea National Health and Nutrition Examination Survey (KNHANES) data and to estimate the rate of missing SES variables from the 4th KNHANES. We searched all original articles published in the KJFM from 2007 to 2011 and identified those that used KNHANES as their primary source of data. None of the 11 articles which presented KNHANES SES variables took into account of omitions in the analysis. The estimated rate of missing data on education, household income, marital status, and occupation data of the 4th KNHANES was 0.3 (0.05)%, 2.7 (0.2)%, 0.5 (0.1)%, and 9.4 (0.9)%, respectively. When all four variables were used simultaneously, the rates increased to 11.8 (0.9)%. Respondents with missing household income tended to be older (P < 0.001), less educated (P < 0.001), and more likely to be unemployed (P < 0.001), and widowed (P < 0.001). A similar relationship was shown for missing occupation data. Omissions in SES variables in KNHANES were related to certain characteristics of study participants. Researchers using KNHANES data should keep in mind the possible bias which can be introduced by missing SES values.

  11. [Salmonella of Indian origin: pseudo-susceptibility to fluoroquinolones].

    PubMed

    Denes, E; Gondran, G; Bezanahary, H; Genet, C; Rogez, J P; Weinbreck, P; Martin, C

    2005-04-01

    We report the case of a patient presenting with typhoid fever after returning from a stay in India. This infection was not cured with a course of ciprofloxacin, due to a reduced susceptibility of the bacteria to the drug. This decreased susceptibility to fluoroquinolones was not detected by the antibiogram, but the MIC for nalidixic acid was greater than 32 mg/l. This case suggests using a third generation cephalosporin instead of a quinolone, for people coming from a high-risk zone. It also suggests that the MIC for nalidixic acid and for norfloxacin can be used as the first clue for a reduced susceptibility to fluoroquinolones.

  12. 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…

  13. Fluoroquinolone-associated tendinopathy.

    PubMed

    Tsai, Wen-Chung; Yang, Yun-Ming

    2011-01-01

    The fluoroquinolones (FQs) are used to treat a wide range of infections because of their excellent gastrointestinal absorption, superior tissue penetration and broad-spectrum activity. Recently, FQ-associated tendinopathy and tendon rupture have been reported, especially in the elderly and patients with diabetes and renal failure. However, these adverse effects do not appear to be widely known among physicians. Because of the frequent use of FQs in clinical practice, physicians should be aware of their potential for severe disability from tendon rupture. Achilles tendinopathy or rupture is among the most serious side effects associated with FQ use, with reports markedly increasing, especially with the use of ciprofloxacin. The histopathologic findings include degenerative lesions, fissures, interstitial edema without cellular infiltration, necrosis and neovascularization. There are possible molecular mechanisms accounting for FQ-associated tendinopathy. First, ciprofloxacin mediates inhibition of cell proliferation and G2/M cell cycle arrest in tendon cells by down-regulation of cyclin B and cyclin-dependent kinase 1. Second, ciprofloxacin inhibits the spead and migration of tenocytes by down-regulation of focal adhesion kinase phosphorylation. Third, ciprofloxacin enhances the enzymatic activity of matrix metalloproteinase-2 with degradation of type I collagen. Management of FQ-associated tendinopathy includes immediate discontinuation of FQs, rest, non-steroidal anti-inflammatory drugs, physical modalities and eccentric strengthening exercise. Tendon rupture may require surgical intervention.

  14. 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.

  15. 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.

  16. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. [4th guidelines on diagnosis and treatment of obesity].

    PubMed

    Jelcić, Jozo; Baretić, Maja; Korsié, Mirko

    2010-01-01

    Obesity is one of the leading public health problems in today's world. The situation is not significantly better in our country. The Republic of Croatia is among the countries with highest prevalence of obesity in the world. All attempts to stop the progression of obesity pandemic have not given satisfactory results up to date. On the other hand, the treatment of obesity is a long-term, exhausting and very complicated process with modest results. From 15th to 18th April 2010 the 4th Croatian Congress on Obesity with international participation was held in Umag with the aim of furthering knowledge about epidemiology, etiopathogenesis, complications and obesity treatment and to provide doctors who treat obesity with opportunity to share insights and experience. The Congress was attended by 200 doctors. At the Congress the Guidelines on Obesity Diagnostics and Treatment were adopted, which will provide practical help to doctors treating patients with obesity.

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

    PubMed

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

    2016-03-01

    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. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  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. Dissociated resistance among fluoroquinolones.

    PubMed Central

    Thomson, K S; Sanders, C C

    1994-01-01

    A panel of 190 clinical isolates of staphylococci, enterococci, Streptococcus pneumoniae, members of the family Enterobacteriaceae, and nonfermentative gram-negative bacilli were examined by agar dilution tests for susceptibility to five quinolones and six nonquinolone agents. Members of the family Enterobacteriaceae and staphylococci were divided into subgroups according to their ciprofloxacin susceptibilities and were analyzed for cross-resistance to OPC-17116, ofloxacin, and temafloxacin. Although the MICs of all quinolones increased with increasing ciprofloxacin resistance, the MICs of OPC-17116, ofloxacin, and temafloxacin tended to increase less than those of ciprofloxacin, indicating that these agents were less affected by the mechanisms of quinolone resistance. An exception to this was the activity of OPC-17116 against highly ciprofloxacin-resistant staphylococci (MIC, > or = 8 micrograms/ml). Some of these staphylococci were equally resistant to OPC-17116, while others were fourfold more susceptible to ciprofloxacin than to OPC-17116. This indicated that in some strains OPC-17116 was more affected than ciprofloxacin by certain mechanisms responsible for high-level resistance. This was paralleled in single-step mutational studies in which 7 of 19 staphylococcal mutants exhibited large decreases in susceptibility to OPC-17116 (128- to 256-fold) but only modest decreases in susceptibility (4- to 16-fold) to the other quinolones. Such mutants were selected only from strains moderately resistant to ciprofloxacin (MIC, > or = 1 microgram/ml). This heterogeneity in the resistance of staphylococci to fluoroquinolones has not been seen previously and suggests that certain mechanisms of resistance in staphylococci affect OPC-17116 to a much greater extent than other quinolones. PMID:7811025

  1. 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

  2. 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.

  3. 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...

  4. Gemifloxacin: a new fluoroquinolone.

    PubMed

    Blondeau, Joseph M; Missaghi, Bayan

    2004-05-01

    Gemifloxacin is a dual targeted fluoroquinolone with potent in vitro activity against Gram-positive, -negative and atypical human pathogens--pathogens considered to be important causes of community-acquired respiratory tract infections. Gemifloxacin demonstrates impressive minimal inhibitory concentrations (MIC 90 ) values against clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Chlamydia pneumoniae and Legionella spp., with MIC 90 values reported to be 0.016-0.06, < 0.0008-0.06, 0.008-0.3, 0.25, 0.125 and 0.016-0.07 microg/ml, respectively. Gemifloxacin is also active in vitro against a broad range of Gram-negative bacilli with MIC 90 values against the Enterobacteriaceae in the range of 0.016 to > 16 microg/ml ( Escherichia coli and Providencia stuartii, respectively), with the majority of the genus having MIC 90 drug concentrations < 0.5 microg/ml. The in vitro activity of gemifloxacin against anaerobic organisms is variable. The MIC values for gemifloxacin are not affected by beta-lactamase production nor by penicillin or macrolide resistance in S. pneumoniae. Gemifloxacin is approved by the FDA to be clinically efficacious against multi-drug resistant S. pneumoniae. The pharmacokinetics of gemifloxacin are such that the drug can be administered orally once-daily to yield or achieve sustainable drug concentrations exceeding the MIC values of clinically important organisms. Gemifloxacin has been shown to target both DNA gyrase (preferred target) and topoisomerase IV (secondary target) - enzymes critical for DNA replication and organism survival - against clinical isolates of S. pneumoniae. This dual targeting activity is thought to be important for reducing the likelihood for selecting for quinolone resistance. Gemifloxacin has been investigated and approved for therapy in patients with community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis. In one study, more patients receiving gemifloxacin

  5. [Current evaluation of the fluoroquinolones].

    PubMed

    Adam, Dieter

    2005-11-24

    Originally, the fluoroquinolones were classified into the groups I-IV on the basis of their clinical field of application, pharmacokinetics, antibacterial spectrum, and bioavailability. In the present publication an evaluation taking account in particular of aspects of clinical application and dosage has been undertaken based on the 1998 classification by a group of PEG experts.

  6. Correlation between levofloxacin consumption and the incidence of nosocomial infections due to fluoroquinolone-resistant Escherichia coli.

    PubMed

    Wu, Hui-Hsiu; Liu, Hsin-Yi; Lin, Yi-Chun; Hsueh, Po-Ren; Lee, Yuarn-Jang

    2016-06-01

    The relationship between fluoroquinolone resistance in Escherichia coli isolates causing nosocomial infection and hospital antibiotic consumption were investigated. Restriction of levofloxacin use was implemented to control the incidence of fluoroquinolone-resistant E coli in the hospital. The study was conducted from January 2004 to December 2010. Antimicrobial agent consumption was obtained from the pharmacy computer system and presented as the defined daily doses per 1000 patient-days every 6 months. The incidence of fluoroquinolone-resistant E coli isolates causing nosocomial infections was obtained from the Department of Infection Control every 6 months. An antimicrobial stewardship program, restricting levofloxacain use, was implemented in July 2007. The incidence of fluoroquinolone-resistant E coli causing nosocomial infections was significantly correlated with fluoroquinolone usage (p = 0.005), but not with the use of third- or fourth-generation cephalosporins, piperacillin-tazobactam, or carbapenems. Parenteral (p = 0.002), oral (p = 0.018), and total levofloxacin (p = 0.001) use were significantly correlated with the extent of fluoroquinolone resistance. With a reduction of levofloxacin use, a decrease of the incidence of fluoroquinolone resistance in E coli isolates was observed. There is a significant correlation between levofloxacin use and the incidence of nosocomial fluoroquinolone-resistant E coli isolates. The incidence of fluoroquinolone-resistant E coli could be reduced by limiting levofloxacin consumption. Copyright © 2011. Published by Elsevier B.V.

  7. PREFACE: The 4th Nordic Meeting on Nuclear Physics

    NASA Astrophysics Data System (ADS)

    Bondorf, Jakob; Hagermann, Gudrun

    1983-01-01

    Nordic meetings on nuclear physics have been held regularly in the various Nordic countries. The 4th Nordic meeting took place in August 16th-20th, 1982, at Fuglsø, situated in the "Mols mountains" in Jylland. The scientific nuclear physics program includes a broad spectrum of topics of current interest to nuclear physicists. The present issue of Physica Scripta covers nearly all the talks presented at the conference. The order of invited talks and contributions follows the conference program closely. We are pleased to have the opportunity to collect some of the highlights of nuclear structure and heavy ion reactions in one volume. The meeting was sponsored by The Nordic Accelerator Committee, NORDITA, The Danish Natural Science Research Council and The Niels Bohr Institute. The financial support from these sources is gratefully acknowledged. The practical organization of the conference was most professionally handled by Bitten Brøndum and Agnethe Elsving. We are indebted to J. Ross Sørensen and his staff at "Fuglsø Centret" for the excellent and comfortable conference and housing facilities. We thank all of our speakers for a smooth cooperation. Last, but not least, we express our gratitude to Nils Robert Nilsson for undertaking the responsibility in editing these proceedings.

  8. 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.

  9. The 4th Concept Detector for the ILC

    NASA Astrophysics Data System (ADS)

    Mazzacane, A.

    2010-05-01

    The 4th Concept Detector is designed for high precision measurements of Physics processes accessible at ILC. It consists of four basic subsystems: a pixel vertex detector for high precision vertex definitions, impact parameter tagging and near-beam occupancy reduction; a cluster-counting low-mass drift chamber for robust pattern recognition with over 100 three-dimensional space-points each with about 55 μm resolution, 3.5% specific ionization measurement; a high precision dual-readout fiber calorimeter, complemented with an EM dual-readout crystal calorimeter, both with time-history readout, for the energy measurement of hadrons, jets, electrons, photons, missing momentum, and the tagging of muons; and, an iron-free dual-solenoid to return the flux and provide a second field region for the inverse direction bending of muons in a gas volume to achieve high acceptance and good muon momentum resolution. All four subsystems separately achieve the important scientific goal to be 2-to-10 times better than the already excellent LEP detectors, Aleph, Delphi, L3, and Opal. All four sub-detector will be described along with their performance and Physics capabilities obtained with full simulation studies.

  10. 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.

  11. PREFACE: 4th International Hadron Physics Conference (TROIA'14)

    NASA Astrophysics Data System (ADS)

    Dağ, Hüseyin; Erkol, Güray; Küçükarslan, Ayşe; Özpineci, Altuğ

    2014-11-01

    The 4th International Conference on Hadron Physics, TROIA'14, was held at Canakkale, Turkey on 1-5 July 2014. Ozyegin University, Middle East Technical University, Canakkale Onsekiz Mart University, Turkish Atomic Energy Authority and HadronPhysics2 Consortium sponsored the conference. It aimed at bringing together the experts and the young scientists working on experimental and theoretical hadron physics. About 50 participants from 10 countries attended the conference. The topics covered included: . Chiral Perturbation Theory . QCD Sum Rules . Effective Field Theory . Exotic Hadrons . Hadron Properties from Lattice QCD . Experimental Results and Future Perspectives . Hadronic Distribution Amplitudes The conference presentations were organized such that the morning sessions contained invited talks and afternoon sessions were devoted to contributed talks. The speakers of the invited talks were: C. Alexandrou, A. Gal, L. Tolos, J.R. Pelaez and M. Schindler. We had also guest speakers D. A. Demir and T. Senger. The conference venue was a resort hotel around Canakkale. As a social program, a guided full-day excursion to the excavation site of the ancient Troia town and Assos was organized. We believe that this conference provided a medium for young scientists and experts in the field to effectively communicate and share ideas. We would like to express our sincere thanks to supporting agencies and to all participants for their contributions and stimulating discussions. We are also grateful to the Scientific Secretary, Bora Işıldak, and all other members of the Organizing Committee for their patience and efforts. 30.10.2014 The Editors

  12. Pseudomonas aeruginosa, Staphylococcus aureus, and fluoroquinolone use.

    PubMed

    MacDougall, Conan; Harpe, Spencer E; Powell, J Patrick; Johnson, Christopher K; Edmond, Michael B; Polk, Ron E

    2005-08-01

    Few long-term multicenter investigations have evaluated the relationships between aggregate antimicrobial drug use in hospitals and bacterial resistance. We measured fluoroquinolone use from 1999 through 2003 in a network of US hospitals. The percentages of fluoroquinolone-resistant Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) were obtained from yearly antibiograms at each hospital. Univariate linear regression showed significant associations between a hospital's volume of fluoroquinolone use and percent resistance in most individual study years (1999-2001 for P. aeruginosa, 1999-2002 for S. aureus). When the method of generalized estimating equations was used, a population-averaged longitudinal model incorporating total fluoroquinolone use and the previous year's resistance (to account for autocorrelation) did not show a significant effect of fluoroquinolone use on percent resistance for most drug-organism combinations, except for the relationship between levofloxacin use and percent MRSA. The ecologic relationship between fluoroquinolone use and resistance is complex and requires further study.

  13. [In vitro antibiotic susceptibility to fluoroquinolones].

    PubMed

    Wong, C A; Galvis, V; Tello, A; Villareal, D; Rey, J J

    2012-03-01

    To determine the antibiotic susceptibility of bacteria recovered from cultures of ocular infections in the Fundación Oftalmológica de Santander - Clínica Carlos Ardila Lulle (FOSCAL). Retrospective descriptive study of a series of registries of cultures of samples from ocular surfaces and intraocular fluids from the OCULAB-FOSCAL laboratory in Floridablanca (Colombia) made between January and December of 2007. Antibiotic sensitivity screening by the method of Kirby-Bauer with impregnated Sensi-Discs™ of determined antibiotic concentrations was performed. A total of 352 samples were studied: 160 from conjunctiva, 150 from cornea and 42 from intraocular fluids. Of the total of the samples more than one microorganism was recovered 45.65% of the samples. Gram positive and Gram negative bacteria were identified in 78.7 and 18.4%, respectively. Resistance to gatifloxacin, moxifloxacin, ciprofloxacin and levofloxacin was observed in 6.3, 8.9, 33.2 and 35.6%, respectively, of Gram positive bacteria. Resistance to gatifloxacin, moxifloxacin, ciprofloxacin and levofloxacin was also observed in 7.4, 16.7, 16.7%and 25.9%, respectively, of Gram negative bacteria. The overall bacterial resistance (Gram positive and Gram negative) to moxifloxacin was 10.15%, and to gatifloxacin it was 6.46%, being which showed a statistically significant difference (P<.05). In our study the development of bacterial resistance to fourth generation fluoroquinolones was demonstrated in ocular samples. However, lower levels of resistance to fourth generation fluoroquinolones compared with that of third and second generation were found, particularly to Gram positive. Gatifloxacin showed lower resistance levels than moxifloxacin. Nevertheless, interpretation of this superiority must be made with caution in the clinical field, since other factors, like tissue penetration and in vivo activity, must be taken into account. Copyright © 2010 Sociedad Española de Oftalmología. Published by Elsevier

  14. 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

  15. Fluoroquinolone-Gyrase-DNA Complexes

    PubMed Central

    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

    2014-01-01

    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-Cys466 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-Gly81 and GyrB-Glu466 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

  16. Urban Infrasound Observations - Examples from July 4th 2012

    NASA Astrophysics Data System (ADS)

    McComas, S.; Hayward, C.; Golden, P.; McKenna, M.; Simpson, C.

    2012-12-01

    , the Heroy Building Rooftop Array, is a two-element 30m line on a single rooftop. Large-scale fireworks displays in Dallas on 4 July 2012 provided an opportunity to identify and characterize known signals in an urban setting. The identified events were associated with one of these fireworks displays about 2 km from the arrays. Signals from these sources were used to tune processing parameters for an automatic coherent detection process, Progressive Multichannel Correlation Method (PMCC). PMCC was then used to scan the data for all possible firework sources in the urban environment and determine temporal, back azimuth, apparent velocity, and frequency information about the sources. The signal frequencies seen were 10-80 Hz and documented the details of the nearly 30 minute firework show. The resulting PMCC analysis showed potential to effectively identify other, lower frequency sources in the urban environment. These data were also is used to characterize the noise environment. Significant roof-to-roof noise differences may be related to the building configurations and mechanical equipment, as well as the interactions of the winds with the structures. During the evening of July 4th , additional ground deployed infrasound gauges provided a comparison of free surface and rooftop measurements. Permission to publish was granted by Director, Geotechnical and Structures Laboratory.

  17. Topical fluoroquinolone use as a risk factor for in vitro fluoroquinolone resistance in ocular cultures.

    PubMed

    Fintelmann, Robert E; Hoskins, Eliza N; Lietman, Thomas M; Keenan, Jeremy D; Gaynor, Bruce D; Cevallos, Vicky; Acharya, Nisha R

    2011-04-01

    To determine whether recent use of topical fluoroquinolones is a risk factor for in vitro fluoroquinolone resistance in Staphylococcus aureus ocular isolates. Disk diffusion susceptibility testing for ciprofloxacin, moxifloxacin, and gatifloxacin was performed for all ocular isolates of S aureus at the Francis I. Proctor Foundation microbiology laboratory from January 1, 2005, to December 31, 2008. The medical records of patients with positive S aureus cultures were reviewed to determine topical or systemic fluoroquinolone use within the 3 months prior to culture. The Fisher exact test was used to compare the proportion of patients who used topical fluoroquinolones in the past 3 months among fluoroquinolone-sensitive and -resistant cases. Logistic regression was used to determine risk factors for fluoroquinolone resistance. Of 200 S aureus cultures, 41 were resistant to ciprofloxacin, moxifloxacin, and gatifloxacin (20.5%). Fluoroquinolone-resistant S aureus isolates were from older patients (mean [SD] age, 65.5 [25.0] years) compared with fluoroquinolone-susceptible isolates (mean [SD] patient age, 52.1 [22.1] years) (P = .003). Use of fluoroquinolones within the 3 months before testing was more frequent in resistant isolates (29%) than in susceptible isolates (11%) (P = .005), as was recent hospitalization (22% of resistant isolates, 0% of susceptible isolates) (P < .001). In the multivariate regression analysis, topical fluoroquinolone use within 3 months was a significant predictor of fluoroquinolone resistance (P = .046), along with age, systemic immunosuppression, and topical fluoroquinolone use between 3 and 6 months before testing. Recent topical fluoroquinolone use is significantly associated with fluoroquinolone resistance in S aureus isolates from ocular cultures.

  18. Topical Fluoroquinolone Use as a Risk Factor for In Vitro Fluoroquinolone Resistance in Ocular Cultures

    PubMed Central

    Fintelmann, Robert E.; Hoskins, Eliza N.; Lietman, Thomas M.; Keenan, Jeremy D.; Gaynor, Bruce D.; Cevallos, Vicky; Acharya, Nisha R.

    2013-01-01

    Objective To determine whether recent use of topical fluoroquinolones is a risk factor for in vitro fluoroquinolone resistance in Staphylococcus aureus ocular isolates. Methods Disk diffusion susceptibility testing for ciprofloxacin, moxifloxacin, and gatifloxacin was performed for all ocular isolates of S aureus at the Francis I. Proctor Foundation microbiology laboratory from January 1, 2005, to December 31, 2008. The medical records of patients with positive S aureus cultures were reviewed to determine topical or systemic fluoroquinolone use within the 3 months prior to culture. The Fisher exact test was used to compare the proportion of patients who used topical fluoroquinolones in the past 3 months among fluoroquinolone-sensitive and -resistant cases. Logistic regression was used to determine risk factors for fluoroquino-lone resistance. Results Of 200 S aureus cultures, 41 were resistant to ciprofloxacin, moxifloxacin, and gatifloxacin (20.5%). Fluoroquinolone-resistant S aureus isolates were from older patients (mean [SD] age, 65.5 [25.0] years) compared with fluoroquinolone-susceptible isolates (mean [SD] patientage, 52.1 [22.1] years) (P=.003). Use of fluoroquinolones within the 3 months before testing was more frequent in resistant isolates (29%) than in susceptible isolates (11%) (P=.005), as was recent hospitalization (22% of resistant isolates, 0% of susceptible isolates) (P<.001). In the multivariate regression analysis, topical fluoroquinolone use within 3 months was a significant predictor of fluoroquinolone resistance (P=.046), along with age, systemic immunosuppression, and topical fluoroquinolone use between 3 and 6 months before testing. Conclusion Recent topical fluoroquinolone use is significantly associated with fluoroquinolone resistance in S aureus isolates from ocular cultures. PMID:21482865

  19. Fluoroquinolones inhibit HCV by targeting its helicase.

    PubMed

    Khan, Irfan A; Siddiqui, Sammer; Rehmani, Sadiq; Kazmi, Shahana U; Ali, Syed H

    2012-01-01

    HCV has infected >170 million individuals worldwide. Effective therapy against HCV is still lacking and there is a need to develop potent drugs against the virus. In the present study, we have employed two culture models to test the activity of fluoroquinolone drugs against HCV: a subgenomic replicon that is able to replicate independently in the cell line Huh-8 and the Huh-7 cell culture model that employs cells transfected with synthetic HCV RNA to produce the infectious HCV particles. Fluoroquinolones have also been shown to have inhibitory activity against certain viruses, possibly by targeting the viral helicase. To tease out the mechanism of the antiviral activity of fluoroquinolones, their effect on HCV NS3 helicase protein was also tested. Huh-7 cells producing the HCV virion as well as Huh-8 cells were grown in the presence or absence of 12 different fluoroquinolones. Afterwards, Huh-7 and Huh-8 cells were lysed and viral RNA was extracted. The extracted RNA was reverse transcribed and quantified by real-time quantitative PCR. Fluoroquinolones were also tested on purified NS3 protein in a molecular-beacon-based in vitro helicase assay. To varying degrees, all of the tested fluoroquinolones effectively inhibited HCV replication in both Huh-7 and Huh-8 culture models. The inhibition of HCV NS3 helicase activity was also observed with all 12 of the fluoroquinolones. Fluoroquinolones inhibit HCV replication possibly by targeting the HCV NS3 helicase. These drugs hold promise for the treatment of HCV infection.

  20. The Use of Systemic and Topical Fluoroquinolones.

    PubMed

    Jackson, Mary Anne; Schutze, Gordon E

    2016-11-01

    Appropriate prescribing practices for fluoroquinolones, as well as all antimicrobial agents, are essential as evolving resistance patterns are considered, additional treatment indications are identified, and the toxicity profile of fluoroquinolones in children has become better defined. Earlier recommendations for systemic therapy remain; expanded uses of fluoroquinolones for the treatment of certain infections are outlined in this report. Prescribing clinicians should be aware of specific adverse reactions associated with fluoroquinolones, and their use in children should continue to be limited to the treatment of infections for which no safe and effective alternative exists or in situations in which oral fluoroquinolone treatment represents a reasonable alternative to parenteral antimicrobial therapy. Copyright © 2016 by the American Academy of Pediatrics.

  1. 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…

  2. 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…

  3. 75 FR 34636 - Safety Zone; Jameson Beach 4th of July Fireworks Display

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-18

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Jameson Beach 4th of July Fireworks Display... temporary safety zone in the navigable waters of Lake Tahoe, for the Jameson Beach 4th of July Fireworks... issued to establish a temporary restricted area in Lake Tahoe, in the vicinity of Jameson Beach at South...

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

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Safety Zone: Macy's July 4th... OF HOMELAND SECURITY (CONTINUED) PORTS AND WATERWAYS SAFETY REGULATED NAVIGATION AREAS AND LIMITED... § 165.166 Safety Zone: Macy's July 4th Fireworks, East River, NY. (a) Regulated area. The following area...

  5. 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...

  6. 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…

  7. 76 FR 37650 - Safety Zone; 4th of July Festival Berkeley Marina Fireworks Display Berkeley, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-28

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; 4th of July Festival Berkeley Marina Fireworks Display Berkeley, CA AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast... Berkeley Pier, Berkeley, CA in support of the 4th of July Festival Berkeley Marina Fireworks...

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

    USDA-ARS?s Scientific Manuscript database

    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...

  9. Bilateral uveitis associated with fluoroquinolone therapy.

    PubMed

    Hinkle, David M; Dacey, Mark S; Mandelcorn, Efrem; Kalyani, Partho; Mauro, John; Bates, James H; Soukasian, Sarkis H; Holland, Gary N; Foster, C Stephen; Fraunfelder, Frederick T; Davis, Janet L; Fraunfelder, Frederick W

    2012-06-01

    Retrospective case series, database study and literature review. Forty case reports are described. To report a possible association between fluoroquinolones and uveitis. Spontaneous reports from the National Registry of Drug-Induced Ocular Side effects, World Health Organization, and Food and Drug Administration were collected on uveitis associated with systemic fluoroquinolone therapy. A literature review was performed using keywords "uveitis", "fluoroquinolones", and each individual fluoroquinolone name. Additional case reports were collected from the practices of six uveitis subspecialists and one neuro-ophthalmologist. Data garnered from the reports include the type of fluoroquinolone, age, gender, adverse drug reaction (ADR), dosage, duration of therapy until onset of uveitis, concomitant drugs, systemic disease, dechallenge and rechallenge data. A total of 40 case reports of uveitis associated with fluoroquinolones were identified including 12 men, 27 women, and 1 case in which the gender was not specified. The median age was 54 years. Dosage varied between the different fluoroquinolone drugs, with the median dosage within the range recommended in the package insert for each different fluoroquinolone. Median time from beginning of therapy to appearance of the ADR was 13 days (range 0-20 days). Thirteen patients were 60 years or older, and one patient was taking systemic anti-inflammatory steroids. There were five positive dechallenge case reports. According to World Health Organization criteria, the relationship between fluoroquinolone therapy and uveitis is "possible". Causality assessments are based on the time relationship of drug administration, uveitis development, and dechallenge data. Clinicians should be aware of a possible bilateral fluoroquinolone-associated uveitis, particularly the finding of iris transillumination and pigment dispersion.

  10. Fluoroquinolone-induced Achilles tendinitis.

    PubMed

    Tam, P K; Ho, Carmen T K

    2014-12-01

    We report a case of Achilles tendinitis after intake of ciprofloxacin for treatment of respiratory tract infection. Fluoroquinolone-induced tendinopathy is an uncommon but increasingly recognised adverse effect of this antibiotic class. Most of the cases occur in the Achilles tendon and may lead to tendon rupture. Possible predisposing risk factors include use of steroid, patients with renal impairment or renal transplant, old age, and being an athlete. The drug should be stopped once this condition is suspected. Symptomatic treatment should be given and orthopaedic referral is desirable if tendon rupture occurs.

  11. Allicin-inspired thiolated fluoroquinolones as antibacterials against ESKAPE pathogens.

    PubMed

    Sheppard, Jordan G; Long, Timothy E

    2016-11-15

    Thiolated fluoroquinolones were synthesized from ciprofloxacin and evaluated for antimicrobial activity against a panel of pathogenic bacteria. Gram-positive species including methicillin-resistant Staphylococcus aureus (MRSA) exhibited the highest level of increased sensitivity toward ciprofloxacin bound with a N-propylthio substituent. Evidence was found that the antibiotics form disulfides with low molecular weight thiols in bacteria and potentiate generation of cytosolic reactive oxygen species (ROS). In final analysis, the enhanced anti-MRSA activity of thiolated fluoroquinolones was attributed to increased cell permeability and reaction with cytosolic thiols that yields an inactive disulfide metabolite and the parent drug ciprofloxacin as an inhibitor of DNA synthesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. 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.

  13. The incidence of fluoroquinolone resistant infections after prostate biopsy--are fluoroquinolones still effective prophylaxis?

    PubMed

    Feliciano, Joseph; Teper, Ervin; Ferrandino, Michael; Macchia, Richard J; Blank, William; Grunberger, Ivan; Colon, Ivan

    2008-03-01

    Fluoroquinolones have been shown to decrease infective complications after prostate biopsy. However, fluoroquinolone resistance is emerging. We quantified contemporary rates of infective complications and the incidence of fluoroquinolone resistant infections after prostate biopsy under fluoroquinolone prophylaxis. We retrospectively evaluated the records of 1,273 patients who underwent prostate biopsy at New York Harbor Veterans Affairs Hospital from January 2004 to December 2006. Patients received levofloxacin or gatifloxacin. Using the Veterans Affairs computerized patient record system we reviewed all patient visits within 1 month after prostate biopsy. Visits were queried for infective symptoms. Positive cultures were evaluated for resistance patterns. The annual and overall incidence of infective complications and fluoroquinolone resistant infections was calculated. Of 1,273 patients 31 (2.4%) presented with infective symptoms after biopsy. The overall incidence of fluoroquinolone resistant infections was 1.2% (15 cases). When stratified by year, there were statistically significant increases in the incidence of infective complications and fluoroquinolone resistance from 2004 to 2006. Of the positive cultures those from 89% of patients yielded Escherichia coli and 90% were fluoroquinolone resistant. Fluoroquinolone resistant E. coli were also resistant to gentamicin in 22% of cases, trimethoprim/sulfamethoxazole in 44%, piperacillin in 72% and ampicillin in 94%. However, 100% sensitivity was demonstrated for amikacin, ceftazidime and ceftriaxone. Fluoroquinolones are still effective as antibiotic prophylaxis for prostate biopsies but there is an increase in infective complications and fluoroquinolone resistance. When patients present with post-prostate biopsy infective symptoms, almost 50% are associated with fluoroquinolone resistant pathogens. Empirical treatment with ceftriaxone, ceftazidime or amikacin should be initiated until culture specific therapy can

  14. 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.

  15. 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.

  16. 18. DETAILED OFFSHORE VIEW OF 4TH TEE, LOOKING NORTHWEST, SHOWING ...

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

    18. DETAILED OFFSHORE VIEW OF 4TH TEE, LOOKING NORTHWEST, SHOWING TRANSITION FROM WOOD BENTS TO CONCRETE BENTS - Huntington Beach Municipal Pier, Pacific Coast Highway at Main Street, Huntington Beach, Orange County, CA

  17. 97. VIEW NORTHWEST OF 4TH FLOOR OF BUILDING 112; NOTE ...

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

    97. VIEW NORTHWEST OF 4TH FLOOR OF BUILDING 112; NOTE REMNANTS OF BEARING SUPPORTS FOR OVERHEAD BELT AND PULLEY POWER TRANSMISSION SYSTEM - Scovill Brass Works, 59 Mill Street, Waterbury, New Haven County, CT

  18. 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

  19. Photogeneration of fluoride by the fluoroquinolone antimicrobial agents lomefloxacin and fleroxacin.

    PubMed

    Martinez, L J; Li, G; Chignell, C F

    1997-03-01

    The photolysis (> 320 nm) of the fluoroquinolone antibacterial agents lomefloxacin and fleroxacin results in the loss of their F3 atoms as fluoride. The quantum yield for lomefloxacin was 0.98 at pH 7.4. The mechanism probably involves aryl-F heterolysis from the S1 state with the concomitant generation of a carbene at C-8. In contrast, the monofluorinated fluoroquinolones norfloxacin and ciprofloxacin do not generate fluoride upon irradiation. Carbenes are highly reactive species that undergo addition, insertion and abstraction reactions and can cause DNA cleavage. These findings may explain why lomefloxacin and fleroxacin are more photomutagenic and photocarcinogenic than fluoroquinolones in which C-8 is either unsubstituted or bears a substituent other than fluorine.

  20. Qualification of the 4th stage propulsor of the Brazilian launcher. SLV: A new sounding rocket

    NASA Astrophysics Data System (ADS)

    Boscov, Jayme; Toyama, Wilson Katsumi

    1989-06-01

    The development of the Satellite Launcher Vehicle (SLV) is presented. In particular, the attention is focused on the acquisition of the propulsion parameters of the 4th stage propulsor. The device feasibility analysis is considered. The system consists of a two staged sounding rocket. Its second stage contains the SVL, which can be launched by the 4th stage propulsor to a height range of about 50 to 60 km.

  1. State-Space Modeling, System Identification and Control of a 4th Order Rotational Mechanical System

    DTIC Science & Technology

    2009-12-01

    SYSTEM IDENTIFICATION AND CONTROL OF A 4th ORDER ROTATIONAL MECHANICAL SYSTEM by Jeremiah P. Anderson December 2009 Thesis Advisor...DATES COVERED Master’s Thesis 4. TITLE AND SUBTITLE State-space Modeling, System Identification and Control of a 4th Order Rotational Mechanical...Educational Control Products is modeled from first principles and represented in state-space form. Identification of the state-space parameters was

  2. [Allergies and adverse events associated with fluoroquinolones].

    PubMed

    Muller, Y; Andrey, D; Emonet, S; Harr, T; Spoerl, D

    2015-04-08

    The prescription ot fluoroquinolones has been constantly increasing over the past decade. consequently, an increasing number of hyper-sensitivity reactions and adverse events have been reported. The aim of the review is to discuss the incidence of hypersensitivity reactions either IgE (immediate) or T cells mediated (delayed). We will make an overview ofthe diagnostic tools available to detect such hypersensitivity reactions. Finally, the specific adverse events associated with fluoroquinolones, including tendinopathy, chondrotoxicity, peripheral neuropathy or retinal detachment will be discussed.

  3. Curricular reform of the 4th year of medical school: the colleges model.

    PubMed

    Slavin, Stuart J; Wilkes, Michael S; Usatine, Richard P; Hoffman, Jerome R

    2003-01-01

    The practice of medicine has changed dramatically over the last 3 decades. Medical education has struggled to keep up with these changes, with only limited success. The 4th year of medical school offers a tremendous opportunity for curricular innovation, but little change has occurred in the past 30 years. This article traces the history of the 4th year, from the Flexnerian era in which the classic preclinical-clinical model for medical education was developed, through the 1970s, when virtually every medical school adopted a largely elective 4th year, to the present. Although the classic 4th-year curriculum has a number of strengths such as flexibility and relative autonomy of scheduling for students, it also has significant weaknesses. A major educational initiative for the 4th year-the "College Phase"-has been implemented at the David Geffen School of Medicine at UCLA. It is designed to remedy many of the weaknesses of the 4th-year curriculum while preserving the benefits. Five colleges have been created: acute care, applied anatomy, medical science, primary care, and urban underserved. Students participate in a number of different college-specific activities that are hoped to produce a more engaging, rigorous, and enriching experience for students and faculty alike

  4. Visible-light-Mediated TiO2 photocatalysis of fluoroquinolone antibacterial agents.

    PubMed

    Paul, Tias; Miller, Penney L; Strathmann, Timothy J

    2007-07-01

    This study reports on the photocatalytic transformation of fluoroquinolone antibacterial agents (ciprofloxacin, enrofloxacin, norfloxacin, and flumequine) in aqueous titanium dioxide (TiO2) suspensions irradiated with ultraviolet (UV; lambda > 324 nm) or visible light (lambda > 400, > 420, or > 450 nm). Visible-light-mediated fluoroquinolone degradation is unexpected from direct photolysis or established TiO2 band gap photoexcitation mechanisms, which both require UV light. Visible-light-mediated photocatalysis requires an appropriate conduction band electron acceptor (e.g., O2, BrO3-), but is not dependent upon hydroxyl radical, superoxide, or other reactive oxygen species generated upon TiO2 band gap excitation. The process slows considerably when fluoroquinolone adsorption is inhibited. Whereas fluoroquinolone decomposition in UV-irradiated TiO2 suspensions is accompanied by mineralization, no changes in dissolved organic carbon occur during visible-light-photocatalyzed degradation. Results are consistent with a proposed charge-transfer mechanism initiated by photoexcitation of surface-complexed fluoroquinolone molecules. Complexation to the TiO2 surface causes a red shift in the fluoroquinolone absorption spectrum (via ligand-to-metal charge transfer), enabling photoexcitation by visible light. Fluoroquinolone oxidation then occurs by electron transfer into the TiO2 conduction band, which delivers the electron to an adsorbed electron acceptor. The lack of organic carbon mineralization indicates formation of stable organic byproducts that are resistant to further degradation by visible light. In UV-irradiated TiO2 suspensions, the charge-transfer mechanism acts in parallel with the semiconductor band gap photoexcitation mechanism.

  5. 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

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

    PubMed

    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.

  7. Fluoroquinolone antibiotics and type 2 diabetes mellitus.

    PubMed

    Telfer, Stephen J

    2014-09-01

    Exposure to fluoroquinolone antibiotics is postulated as a risk factor for subsequent development of type 2 diabetes. It is hypothesized that fluoroquinolones induce an intracellular magnesium deficit that can lead to insulin resistance. A temporal correlation is reported between the rate of outpatient prescription of quinolones and the incidence of diabetes during the period 1980-2011 with a lag of approximately two years (R(2)=0.86, P<10(-9)). The increase in incidence of diabetes after 1990 and the recent decrease in the number of new cases are both reflected in the fluoroquinolone prescription rates. A geographical correlation is reported (adj. R(2)=0.7, P<0.0001) between rates of increase in prevalence of diabetes in each U.S. state and a model using only local rates of outpatient fluoroquinolone prescription, local rates of increase in the prevalence of obesity, and local rates of population growth as predictor variables. Prescription rates of non-quinolone antibiotics correlated less well with the local rates of increase in prevalence of diabetes. The data are consistent with fluoroquinolone exposure predisposing an individual to develop diabetes with a probability that strongly depends upon factors that also lead to an increase in obesity. According to the hypothesis, much of the increase in the incidence of type 2 diabetes in the U.S. from 1990 to the present can be attributed to fluoroquinolone exposure. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

  8. Risk factors associated with fluoroquinolone-resistant enterococcal urinary tract infections in a tertiary care university hospital in north India.

    PubMed

    Banerjee, Tuhina; Anupurba, Shampa

    2016-10-01

    Fluoroquinolone resistance in both Gram-positive and Gram-negative bacteria has increased with the widespread use of fluoroquinolones. Fluoroquinolone resistance in Gram-negative bacilli has been widely studied, though staphylococci and enterococci are also notably resistant. Enterococci being the second most common cause of healthcare-associated urinary tract infections (UTIs) fluoroquinolones are often the drug of choice. This study was undertaken to assess the risk factors associated with fluoroquinolone-resistant enterococcal UTI in a tertiary level health facility in north India. A total of 365 patients with UTI caused by enterococci were studied over a period of two years. Patients with ciprofloxacin-resistant and susceptible UTI were considered as cases and controls, respectively. Resistance profile of the isolates against common antibiotics was studied by minimum inhibitory concentration (MIC) determination. Mechanisms for fluoroquinolone resistance was studied by efflux pump inhibitor activity and multiplex PCR targeting the qnr genes. A total of 204 (55.89%) cases and 161 (44.1%) controls were identified. The fluoroquinolone-resistant isolates were significantly resistant to ampicillin, high strength aminoglycosides and vancomycin. The majority (78%) of the resistant isolates showed efflux pump activity. Treatment in indoor locations, presence of urinary catheters and pregnancy along with recent exposure to antibiotics especially fluoroquinolones, third generation cephalosporins and piperacillin-tazobactam were identified as independent risk factors. Our results showed that fluoroquinolone resistance in enterococcal UTI was largely associated with indoor usage of antibiotics and use of indwelling devices. Knowledge of risk factors is important to curb this emergence of resistance.

  9. 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.

  10. Declining susceptibilities of gram-negative bacteria to the fluoroquinolones: effects on pharmacokinetics, pharmacodynamics, and clinical outcomes.

    PubMed

    Labreche, Matthew J; Frei, Christopher R

    2012-11-01

    Published evidence of rising gram-negative bacterial resistance to fluoroquinolone therapy is reviewed, with a focus on the potential need for revising pharmacokinetic-pharmacodynamic (PK-PD) targets in order to maintain acceptable clinical outcomes. With a more than threefold increase in fluoroquinolone use among U.S. adults since the introduction of second- and third-generation (i.e., "respiratory") fluoroquinolones 15 years ago, surveillance data indicate a decline in some gram-negative organisms' susceptibility to this antimicrobial class. These trends have raised concerns that the need to attain higher organism-specific minimum inhibitory concentrations (MICs) may lead to worse patient outcomes, even when MIC values are below current established "clinical breakpoints" for fluoroquinolone susceptibility. A growing body of evidence from PK-PD studies suggests that current fluoroquinolone dosing regimens are no longer adequate to achieve validated PK-PD targets. For example, a Monte Carlo simulation using PK data from U.S. hospitals showed decreasing rates of response to standard ciprofloxacin and levofloxacin i.v. dosing regimens among patients treated for infections with Escherichia coli and Klebsiella species. These findings suggest that currently accepted PK-PD targets may need to be revised for certain patient populations, including patients with bloodstream infections (BSIs). More research is needed to confirm the appropriateness of adjusting clinical breakpoints and other strategies to combat rising fluoroquinolone resistance. The use of the fluoroquinolones has markedly increased since the introduction of the respiratory fluoroquinolones. Surveillance data and PK-PD studies have raised concerns about suboptimal patient outcomes with the use of fluoroquinolones for some gram-negative infections, particularly BSIs. PK-PD goals and clinical breakpoints may need to be revised for these infections.

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

    PubMed Central

    Yassien, M.A.M.; Elfaky, M.A.

    2015-01-01

    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

  12. Risk factors associated with fluoroquinolone-resistant enterococcal urinary tract infections in a tertiary care university hospital in north India

    PubMed Central

    Banerjee, Tuhina; Anupurba, Shampa

    2016-01-01

    Background & objectives: Fluoroquinolone resistance in both Gram-positive and Gram-negative bacteria has increased with the widespread use of fluoroquinolones. Fluoroquinolone resistance in Gram-negative bacilli has been widely studied, though staphylococci and enterococci are also notably resistant. Enterococci being the second most common cause of healthcare-associated urinary tract infections (UTIs) fluoroquinolones are often the drug of choice. This study was undertaken to assess the risk factors associated with fluoroquinolone-resistant enterococcal UTI in a tertiary level health facility in north India. Methods: A total of 365 patients with UTI caused by enterococci were studied over a period of two years. Patients with ciprofloxacin-resistant and susceptible UTI were considered as cases and controls, respectively. Resistance profile of the isolates against common antibiotics was studied by minimum inhibitory concentration (MIC) determination. Mechanisms for fluoroquinolone resistance was studied by efflux pump inhibitor activity and multiplex PCR targeting the qnr genes. Results: A total of 204 (55.89%) cases and 161 (44.1%) controls were identified. The fluoroquinolone-resistant isolates were significantly resistant to ampicillin, high strength aminoglycosides and vancomycin. The majority (78%) of the resistant isolates showed efflux pump activity. Treatment in indoor locations, presence of urinary catheters and pregnancy along with recent exposure to antibiotics especially fluoroquinolones, third generation cephalosporins and piperacillin-tazobactam were identified as independent risk factors. Interpretation & conclusions: Our results showed that fluoroquinolone resistance in enterococcal UTI was largely associated with indoor usage of antibiotics and use of indwelling devices. Knowledge of risk factors is important to curb this emergence of resistance. PMID:28256471

  13. Sale of fluoroquinolones in northern Tanzania: a potential threat for fluoroquinolone use in tuberculosis treatment.

    PubMed

    van den Boogaard, Jossy; Semvua, Hadija H; Boeree, Martin J; Aarnoutse, Rob E; Kibiki, Gibson S

    2010-01-01

    Fluoroquinolones have a potential role in shortening tuberculosis (TB) treatment duration. They are currently used in the treatment of other infections. This has raised concerns about development of mycobacterial resistance. The current study evaluates the sale of fluoroquinolones (among other antibacterials) in Moshi, Tanzania, a country with one of the highest burdens of TB in the world. Trained pharmacy assistants registered the sale of fluoroquinolones during February and March 2009 to outpatients in Moshi in all 14 pharmacies that are authorized to sell antibacterials for systemic use. The sale of all antibacterials of the Anatomical Therapeutic Chemical (ATC) J01 class was expressed in defined daily doses (DDDs) per 1000 inhabitants per day (DID). The availability of fluoroquinolones in drug outlets that are not authorized to sell antibacterials for systemic use was assessed in 15 randomly selected outlets in Moshi. The sale of antibacterials to outpatients in Moshi by authorized pharmacies was 4.99 DID. The sale of fluoroquinolones was 0.62 DID (12% of total antibacterial sales). Ciprofloxacin was available in all 15 unauthorized drug outlets. The substantial sales of fluoroquinolones by authorized pharmacies and the wide availability of fluoroquinolones in unauthorized drug outlets in Moshi constitute a challenge to the use of fluoroquinolones in TB treatment in Tanzania. Control of antibacterial use in Tanzania requires the implementation of surveillance systems for antibacterial use and resistance, and adequate restriction of antibacterial sales to authorized pharmacies only.

  14. Oral Fluoroquinolones and the Risk of Uveitis.

    PubMed

    Sandhu, Harpal Singh; Brucker, Alexander J; Ma, Liyuan; VanderBeek, Brian L

    2016-01-01

    Fluoroquinolones are the most commonly prescribed antibiotic class in the outpatient setting. Recent reports have implicated an association between oral fluoroquinolones and an increased risk of uveitis. To determine the hazard of uveitis with oral fluoroquinolone use. A retrospective cohort study was conducted using medical claims data from a large national US insurer (N = 4,387,651). Cohorts from ambulatory care centers across the United States were created including every new user of an oral fluoroquinolone or β-lactam antibiotic prescription with at least 24 months of data prior to the date of the prescription from January 1, 2000, to January 30, 2013. Exclusion criteria consisted of any previous diagnosis of uveitis or a uveitis-associated systemic illness. Participants were censored for a new diagnosis of a uveitis-associated systemic illness, the end of an observation period, use of the other class of antibiotic, or removal from the insurance plan. Data analysis was performed from January 2 through March 15, 2015. The hazard of a uveitis diagnosis after a fluoroquinolone prescription compared with a β-lactam prescription using multivariate regression with Cox proportional hazards models. Of the 4,387,651 patients in the database, 843,854 individuals receiving a fluoroquinolone and 3,543,797 patients receiving a β-lactam were included in the analysis. After controlling for age, race, and sex using multivariate analysis, no hazard for developing uveitis at the 30-, 60-, or 90-day observation windows was seen (hazard ratio [HR] range, 0.96; 95% CI, 0.82-1.13; to 1.05; 95% CI, 0.95-1.16; P > .38 for all comparisons). The 365-day observation period showed a small increase in the HR for the fluoroquinolone cohort (1.11; 95% CI, 1.05-1.17; P < .001). Moxifloxacin produced an increased hazard for uveitis at every time point (HR range, 1.47-1.75; 95% CI, 1.27-2.37; P < .001 for all comparisons). Secondary analysis demonstrated a similar hazard at 365 days for a

  15. Systematically frameshifting by deletion of every 4th or 4th and 5th nucleotides during mitochondrial transcription: RNA self-hybridization regulates delRNA expression.

    PubMed

    Seligmann, Hervé

    2016-01-01

    In mitochondria, secondary structures punctuate post-transcriptional RNA processing. Recently described transcripts match the human mitogenome after systematic deletions of every 4th, respectively every 4th and 5th nucleotides, called delRNAs. Here I explore predicted stem-loop hairpin formation by delRNAs, and their associations with delRNA transcription and detected peptides matching their translation. Despite missing 25, respectively 40% of the nucleotides in the original sequence, del-transformed sequences form significantly more secondary structures than corresponding randomly shuffled sequences, indicating biological function, independently of, and in combination with, previously detected delRNA and thereof translated peptides. Self-hybridization decreases delRNA abundances, indicating downregulation. Systematic deletions of the human mitogenome reveal new, unsuspected coding and structural informations.

  16. Support for the 4th Pan-American Congress on Plants and Bioenergy

    SciTech Connect

    Carpita, Nicholas C.

    2016-01-25

    Intellectual Merit: Following the success of the first three Pan-American Congresses on Plants and BioEnergy held biennially, the 4th congress will be held at the University of Guelph, Canada June 4-7, 2014. We aim to continue a tradition of showcasing major advances in energy crop improvement yet keep in perspective the realities of the economic drivers and pressures that govern the translation of scientific success into a commercial success. The congress is endorsed by the American Society of Plant Biologists and the Canadian Society of Plant Biologists. The program will cover a range of disciplines, including algal and plant systems for bioenergy, plant genetics and genomics, gene discovery for improvement of bioenergy production and quality, regulatory mechanisms of synthesis and degradation, strategies for 3rd generation biofuel production and the promise of synthetic biology in production of biofuels and bio-based products, cropping systems and productivity for biomass production, and mitigation of environmental impacts of bioenergy production. Broader Impacts: We are requesting support to generate stipends for domestic and permanent-resident students, post-doctorals, and pre-tenured faculty members to attend and benefit from the outstanding program. The stipends will be limited to registration and on-site lodging costs, with partial support for travel in instances of great need. So that as great a number can benefit as possible, airfare costs will be provided for only applicants with great need. ASPB has endorsed this meeting and will assist in advertising and promoting the meeting. ASPB has a long-standing commitment to increase participation and advance the careers in plant biology of women, minorities and underrepresented scientists, and they will assist us in identifying worthy candidates.

  17. Identification of Gifted Children: A Comparison of the Scores on Stanford-Binet 4th Edition and Form LM.

    ERIC Educational Resources Information Center

    Kluever, Raymond C.; Green, Kathy E.

    1990-01-01

    Composite scores for 51 gifted children (ages 3-12) on the Stanford-Binet LM were found to be significantly higher than scores on the Stanford-Binet 4th Edition. Correlations between the LM total and 4th Edition area scores were significant. Results suggest that the 4th Edition composite score cut-off value for assessing giftedness may require…

  18. Methods for analysis of fluoroquinolones in biological fluids

    USDA-ARS?s Scientific Manuscript database

    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....

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

    USDA-ARS?s Scientific Manuscript database

    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) ...

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. Mechanisms of fluoroquinolone resistance in Mycobacterium tuberculosis.

    PubMed

    Yujiao, Zhang; Xiaojing, Li; Kaixia, Mi

    2016-10-20

    Tuberculosis, caused by the pathogen Mycobacterium tuberculosis, is one of the world's deadliest bacterial infectious disease. It is still a global-health threat, particularly because of the drug-resistant forms. Fluoroquinolones, with target of gyrase, are among the drugs used to treat tuberculosis. However, their widespread use has led to bacterial resistance. The molecular mechanisms of fluoroquinolone resistance in mycobacterium tuberculosis have been reported, such as DNA gyrase mutations, drug efflux pumps system, bacterial cell wall thickness and pentapeptide proteins (MfpA) mediated regulation of gyrase. Mutations in gyrase conferring quinolone resistance play important roles and have been extensively studied. Recent studies have shown that the regulation of DNA gyrase affects mycobacterial drug resistance, but the mechanisms, especially by post-translational modification and regulatory proteins, are poorly understood. In this review, we summarize the fluoroquinolone drug development, and the molecular genetics of fluoroquinolone resistance in mycobacteria. Comprehensive understanding of the mechanisms of fluoroquinolone resistance in Mycobacterium tuberculosis will open a new view on understanding drug resistance in mycobacteria and lead to novel strategies to develop new accurate diagnosis methods.

  5. The safety profile of the fluoroquinolones.

    PubMed

    Bertino, J; Fish, D

    2000-07-01

    Premarketing trials showed the fluoroquinolone agents to have a favorable side-effect profile, with treatment-related adverse events comprising gastrointestinal, central nervous system, and dermatologic effects that were generally mild and reversible on cessation of treatment. However, postmarketing surveillance studies have identified severe adverse events, including severe anaphylaxis, QTc-interval prolongation, and potential cardiotoxicity, associated with 3 quinolone agents that either resulted in the removal of the agent from the market (temafloxacin and grepafloxacin) or significantly restricted its use due to substantial mortality and morbidity associated with liver toxicity (trovafloxacin). To date, there have been no such significant adverse events associated with the older fluoroquinolone agents, including ciprofloxacin, ofloxacin, norfloxacin, and levofloxacin. However, there are fewer data from postmarketing surveillance studies on the most recently approved agents, such as moxifloxacin and gatifloxacin, or agents awaiting approval, such as gemifloxacin. This paper examines safety data from the premarketing trials and postmarketing surveillance studies of fluoroquinolones available in the United States. A MEDLINE search was performed to identify all English-language studies published since 1980 concerning the safety profiles of the fluoroquinolones. The fluoroquinolone antibacterial agents offer broad-spectrum therapy in patients with a variety of infections. Given similar spectra of activity, the choice between quinolones may be based on differences in efficacy and safety or tolerability profiles. Most drug reactions involving these agents are minor and reversible on discontinuing treatment, but adverse effects can be associated with significant mortality and morbidity, as was seen in the case of trovafloxacin and temafloxacin.

  6. Mode of Action of Sulfanilyl Fluoroquinolones

    PubMed Central

    Alovero, Fabiana; Nieto, Marcelo; Mazzieri, Maria Rosa; Then, Rudolf; Manzo, Ruben H.

    1998-01-01

    The mode of action of sulfanilyl fluoroquinolones (NSFQs) was investigated with NSFQ-104, NSFQ-105, and some structurally related compounds. Evidence arising from interactions with p-aminobenzoic acid and trimethoprim suggested that a sulfonamidelike mechanism of action makes little or no contribution to the in vitro activity of NSFQs. NSFQ-105 showed an activity that inhibits gyrase-catalyzed DNA supercoiling that is similar to the activity of other fluoroquinolones. Also, NSFQ-105 uptake was decreased by the presence of Mg2+ and increased by a lower pH. These results indicate that NSFQs having only one ionizable group could exhibit more favorable kinetics of access to the bacterial cell than zwitterionic fluoroquinolones. PMID:9624501

  7. Seismically induced liquefaction structures in La Magdalena archaeological site, the 4th century AD Roman Complutum (Madrid, Spain)

    NASA Astrophysics Data System (ADS)

    Rodríguez-Pascua, M. A.; Silva, P. G.; Perucha, M. A.; Giner-Robles, J. L.; Heras, C.; Bastida, A. B.; Carrasco, P.; Roquero, E.; Lario, J.; Bardaji, T.; Pérez-López, R.; Elez, J.

    2016-10-01

    The ancient Roman city of Complutum (Alcalá de Henares, Madrid), founded in the 1st century AD, was one of the most important cities of Hispania. The old Roman city was destroyed, abruptly abandoned, relocated close by and rebuilt during the late 4th century AD. Destruction of the city and its relocation has not yet been explained by archaeologists. In this paper, with our multidisciplinary approach, we identify and characterize earthquake archaeological effects (EAEs) affecting the archaeological site, the La Magdalena, an agricultural holding 4 km from the core of Complutum. The most important EAEs in the site are liquefactions (sand dikes and explosive sand-gravel craters) affecting Roman structures, such as water tanks (cisterns), houses and graves. Ground liquefaction generated significant ground cracks, explosive craters and folds in foundations of buildings. Several other Roman sites throughout the valley were also abandoned abruptly during the 4th century AD, in some cases with EAEs of similar origin. This suggests the occurrence of a 5.0-6.6 Mw seismic event in the zone, in accordance with the minimum empirical limit of seismically-induced liquefaction and the maximum surface rupture length of the Henares fault.

  8. Oral fluoroquinolones and risk of glaucoma.

    PubMed

    Yang, Louis; Etminan, Mahyar; Mikelberg, Frederick S

    2014-09-01

    To evaluate the risk of developing glaucoma in patients taking systemic fluoroquinolones. A case-control study was carried out among a cohort of subjects who had visited an ophthalmologist in the Province of British Columbia, Canada from 2000 to 2007. Cases were identified as those newly diagnosed with glaucoma (ICD-9 360). For each case, 5 controls were selected and matched to the cases by age and calendar time. Crude and adjusted rate ratios (RRs) for current, recent, past, and distant use of fluoroquinolones were calculated. From the cohort of 989,591 subjects, 178,264 subjects were diagnosed with glaucoma and 891,320 were corresponding controls. The 2 groups had same average age of 65 and comparable systemic comorbidities including hypertension, coronary artery disease, and diabetes. There was no statistically significant association between the use of systemic fluoroquinolones and the development of glaucoma for current use [RR=1.01 (95% confidence interval (CI), 0.95-1.07)], recent use [RR=1.00 (95% CI, 0.92-1.08)], or past use [RR=0.94 (95% CI, 0.90-1.00)]. Distant use of systemic fluoroquinolones had a small statistically significant increased risk of developing glaucoma [RR=1.12 (95% CI, 1.09-1.14)]. There was no detected increased association of the development of glaucoma with current, recent, or past use of systemic fluoroquinolone but a minimal statistically significant increased risk was associated with distant use. Future studies should further examine a potential delayed response with fluoroquinolones and glaucoma.

  9. Evaluation of several fluoroquinolones and beta-lactams in terms of their capability to restrict the selection of fluoroquinolone-resistant Salmonella: in vitro models.

    PubMed

    Cebríán, L; Rodríguez, J C; Escribiano, I; Royo, S G

    2007-12-01

    With a view to understanding the interaction between Salmonella and the drugs used to treat it, our aim was to compare the different capacities of various antibiotics to generate mutants resistant to fluoroquinolones following repeated exposure of the microorganisms to subinhibitory concentrations of these drugs. Mutants were generated by repeated exposure to fluoroquinolones and beta-lactams. In order to compare the different capacity to generate resistant mutants, we studied the minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) of the wild-type strains and of the mutants generated. These data were compared with pharmacokinetic parameters. Mutants generated following repeated exposure to fluoroquinolones exhibit an increased MPC as compared to the wild-type strains, both in strains that are nalidixic acid susceptible and in those that are nalidixic acid resistant, with repeated exposure to ciprofloxacin leading to the smallest increases. This increase in MPC is gradual and depends on the number of exposures the bacteria are subjected to. It results in a decrease in the AUC/MPC ratio, although the absolute values vary. Ciprofloxacin is the most active drug, both against nalidixic acid-susceptible and nalidixic acid-resistant strains, although in late mutants of originally nalidixic acid-resistant strains, the AUC/MPC values are low. Repeated exposure to amoxicillin and cefotaxime also produces an increase in the MPC of fluoroquinolones, with ciprofloxacin being the least affected. Exposure to amoxicillin leads to the greatest increase in the MPC of fluoroquinolones. When the AUC/MPC ratios of these mutants are compared, the values are still seen to be high (between 25 and 75). When we compare the MPC data with the antibiotic levels in humans following administration of the usual doses, it can be seen that ciprofloxacin exhibits the highest AUC/MPC and therefore the lowest risk of therapeutic failures. In addition, administration of

  10. Parents in Partnership for Proficiency: For 3rd & 4th Graders and Their Families.

    ERIC Educational Resources Information Center

    Neiner, Christine; And Others

    This document contains a series of learning materials for 3rd and 4th graders and their families. The materials are designed to augment classroom learning. Included are worksheets, games, and other skill building activities for writing, reading, math, citizenship, and science. These activities are meant to help children prepare for proficiency…

  11. 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...

  12. 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…

  13. 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…

  14. 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

  15. 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...

  16. 75 FR 33170 - Safety Zone; City of Martinez 4th of July Fireworks, Martinez, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-11

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; City of Martinez 4th of July Fireworks, Martinez, CA AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast Guard is establishing a temporary safety zone for the launching of fireworks being sponsored by the City of Martinez...

  17. 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…

  18. 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

  19. Relationships between Grade Levels, Personal Factors, and Instructional Variation among 4th-12th Grade Teachers

    ERIC Educational Resources Information Center

    White, Jacquelyn M.

    2011-01-01

    The purpose of this quantitative correlational study was to investigate relationships between grade levels, personal factors of teachers, and instructional variety used by 4th-12th grade teachers in Kern County, California. The population under investigation included 2,844 teachers. 235 elementary, middle school/junior high, and secondary teachers…

  20. 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

  1. Using 4th order Runge-Kutta method for solving a twisted Skyrme string equation

    NASA Astrophysics Data System (ADS)

    Hadi, Miftachul; Anderson, Malcolm; Husein, Andri

    2016-03-01

    We study numerical solution, especially using 4th order Runge-Kutta method, for solving a twisted Skyrme string equation. We find numerically that the value of minimum energy per unit length of vortex solution for a twisted Skyrmion string is 20.37 × 1060 eV/m.

  2. 33 CFR 165.166 - Safety Zone: Macy's July 4th Fireworks, East River, NY.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 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 area...) in length, carrying persons for the purpose of viewing the fireworks, may take position in an...

  3. 33 CFR 165.166 - Safety Zone: Macy's July 4th Fireworks, East River, NY.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 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 area...) in length, carrying persons for the purpose of viewing the fireworks, may take position in an...

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

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 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 area...) in length, carrying persons for the purpose of viewing the fireworks, may take position in an...

  5. 33 CFR 165.166 - Safety Zone: Macy's July 4th Fireworks, East River, NY.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 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 area...) in length, carrying persons for the purpose of viewing the fireworks, may take position in an...

  6. Polarimetric Microwave Emission from Snow Surface: 4th Strokes Component Analysis

    USDA-ARS?s Scientific Manuscript database

    The effect of ice on the polarimetric 4th Stokes component observations is investigated using WindSat data over Antarctica. The difference in the magnitude of the signal observed during (July 2003) and summer (February 2004) months is investigated using a second harmonic sine function of the azimuth...

  7. 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

  8. 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

  9. SAR analysis of new dual targeting fluoroquinolones. Implications of the benzenesulfonyl group.

    PubMed

    Nieto, Marcelo J; Pierini, Adriana B; Singh, Nidhi; McCurdy, Christopher R; Manzo, Ruben H; Mazzieri, María R

    2012-05-01

    When a benzenesulfonyl moiety (BS) was bound to the N-piperazinyl ring of antibacterial fluoroquinolones (AMFQs) norfloxacin (NOR) or ciprofloxacin (CIP), the resulting benzenesulfonyl-fluoroquinolone (BSFQs) analogs showed an improved in vitro activity against Gram-positive strains. A bioisosterical replacement of the sulfonyl group for a carbonyl group led to the benzenecarboxamide-fluoroquinolones (BCFQs) that showed a similar trend in the antibacterial activity and spectrum. The BSFQs and BCFQs are considered members of the "dual targeting" fluoroquinolones, targeting both DNA gyrase and topoisomerase IV. To disclose the real contribution of the BS/BC moiety in anti-staphylococcal activity, a 3D-QSAR analysis that included calculation of theoretical molecular descriptors and pharmacophore generation was performed. Previous and present QSAR results have confirmed the positive influence on activity of small electron donating p-substituent on the BS or BC moiety. The generated phamacophore model showed that both phenyl and SO2/CO groups are involved in the interaction with receptor. We postulate that the enhanced potency of BSFQs against Staphylococcus aureus compared to CIP and NOR could be caused by the presence of the BS moiety that resulted in enhanced binding to DNA gyrase of Sa. Additionally, their greater ability to enter bacterial cells by diffusion and a reduced susceptibility to FQ-specific efflux pumps could also make a contribution.

  10. Antitrypanosomal Activities of Fluoroquinolones with Pyrrolidinyl Substitutions

    PubMed Central

    Nenortas, Elizabeth; Kulikowicz, Tomasz; Burri, Christian; Shapiro, Theresa A.

    2003-01-01

    Fluoroquinolones with pyrrolidinyl substitutions were tested against Trypanosoma brucei and mammalian cells. Bulky substituents at C-7 or a 1-2-bridging thiazolidine ring increased antitrypanosomal activity and selective toxicity. These compounds trap protein-DNA complexes and inhibit nucleic acid biosynthesis in trypanosomes, characteristics of topoisomerase II inhibition. PMID:12937017

  11. [Fluoroquinolone-induced Achilles tendon rupture].

    PubMed

    Maurin, N

    2008-02-01

    A 72-year-old female dialysis patient with insulin-dependent diabetes mellitus who was under long-term medication with oral prednisolone due to chronic obstructive pulmonary disease was given levofloxacin for one week to treat an acute bronchitis (one 500 mg dose on the first day, 125 mg/day orally from second day onwards). One day after the end of levofloxacin treatment, the patient complained about a constant dragging pain above the right heel that receded under local application of diclofenac ointment and inactivity of the right foot. Twelve days after ending administration of levofloxacin, strong pains in the right calf were suddenly felt during normal walking, and active plantar flexion was lost. Palpation showed the right calf to be soft; a distinct gap was found in the middle third of the Achilles tendon. The Thompson test was positive, and the patient was unable to stand on her right toes. Ultrasonography showed a discontinuity of the right Achilles tendon. A spontaneous Achilles tendon rupture after taking fluoroquinolone was diagnosed. Conservative treatment was applied due to the reduced general condition. Initial treatment involved a below-knee plaster cast in equinus position; the cast was replaced on the fourth day by a pneumatic walker, which was also worn during mobilisation by physiotherapy. A typical feature of fluoroquinolone-induced tendinopathy (FIT) is a considerable latency period in some cases between the commencement of treatment with a fluoroquinolone and the onset of FIT symptoms. In addition to fluoroquinolone intake, there are three other predisposing risk factors for tendinopathy: age over 60 years, long-term treatment with systemic glucocorticoids, and chronic kidney disease. The patient showed a combination of all the aforementioned risk factors. In patients with these risk factors, especially among people with a combination of said risk factors - which is frequently the case with nephrologic and dialysis patients, especially

  12. DNA repair inhibition by UVA photoactivated fluoroquinolones and vemurafenib.

    PubMed

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

    2014-12-16

    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. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  13. Radiation-induced in vitro phototoxic potential of some fluoroquinolones.

    PubMed

    Ray, R S; Agrawal, N; Misra, R B; Farooq, M; Hans, R K

    2006-01-01

    Photosensitizing drugs that can damage cellular biomolecules is a matter of concern. Lomefloxacin, norfloxacin, ofloxacin, and enoxacin (broad-spectrum antibiotics of fluoroquinolone group) are used for the treatment of Gram-positive and Gram-negative bacterial infections. Phototoxicity and possible mechanism of their action was assessed under the exposure of ambient levels of UV-A, UV-B, and sunlight at a concentration generally used in the treatment of various diseases. Singlet oxygen (1O2), superoxide anion radical (O2.-) generation, DNA damage, and lipid peroxidation in human blood were studied. All the fluoroquinolones tested in this study produced 1O2 and O2.- under exposure to UV-A, UV-B, and sunlight depending on the concentrations (0 to 60 microg/mL) of the drugs. Enoxacin showed a higher yield of 1O2 and O2.- than other drugs. These materials also degraded deoxyguanosine and induced lipid peroxidation in vitro under exposure to UV-A, UV-B, and sunlight (depending on the dose of radiation). The formation of the reactive oxygen species (ROS) by the photoexcited drugs may be considered as a possible mechanism of their action.

  14. 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

  15. A Generalized 4th-Order Runge-Kutta Method for the Gross-Pitaevskii Equation

    NASA Astrophysics Data System (ADS)

    Kandes, Martin

    2015-04-01

    We present the implementation of a method-of-lines approach for numerically approximating solutions of the time-dependent Gross-Pitaevksii equation in non-uniformly rotating reference frames. Implemented in parallel using a hybrid MPI + OpenMP framework, which will allow for scalable, high-resolution numerical simulations, we utilize an explicit, generalized 4th-order Runge-Kutta time-integration scheme with 2nd- and 4th-order central differences to approximate the spatial derivatives in the equation. The principal objective of this project is to model the effect(s) of inertial forces on quantized vortices within weakly-interacting dilute atomic gas Bose-Einstein condensates in the mean-field limit of the Gross-Pitaevskii equation. Here, we discuss our work-to-date and preliminary results.

  16. 4th European Seminars in Virology on Oncogenic and Oncolytic Viruses, in Bertinoro (Bologna), Italy.

    PubMed

    Reale, Alberto; Messa, Lorenzo; Vitiello, Adriana; Loregian, Arianna; Palù, Giorgio

    2017-10-01

    The 4th European Seminars in Virology (EuSeV), which was focused on oncogenic and oncolytic viruses, was held in Bertinoro (Bologna), Italy, from June 10 to 12, 2016. This article summarizes the plenary lectures and aims to illustrate the main topics discussed at 4th EuSeV, which brought together knowledge and expertise in the field of oncogenic and oncolytic viruses from all over the world. The meeting was divided in two parts, "Mechanisms of Viral Oncogenesis" and "Viral Oncolysis and Immunotherapy," which were both focused on dissecting the complex and multi-factorial interplay between cancer and human viruses and on exploring new anti-cancer strategies. J. Cell. Physiol. 232: 2641-2648, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Effects of Public Preschool Expenditures on the Test Scores of 4th Graders: Evidence from TIMSS

    PubMed Central

    Waldfogel, Jane; Zhai, Fuhua

    2011-01-01

    This study examines the effects of public preschool expenditures on the math and science scores of 4th graders, holding constant child, family, and school characteristics, other relevant social expenditures, and country and year effects, in seven Organization for Economic Co-operation and Development (OECD) countries -- Australia, Japan, Netherlands, New Zealand, Norway, U.K., and U.S -- using data from the 1995 and 2003 Trends in International Mathematics and Science Study (TIMSS). Our results indicate that there are small but significant positive effects of public preschool expenditures on the math and science scores of 4th graders and preschool expenditures reduce the risk of children scoring at the low level of proficiency. We also find some evidence that children from low-resource homes and homes where the test language is not always spoken may tend to gain more from increased public preschool expenditures than other children,. PMID:21442008

  18. 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

  19. LESSONS LEARNED, HEADQUARTERS, 4TH BATTALION (AW)(SP), 60TH ARTILLERY

    DTIC Science & Technology

    The 4th Battalion (AW)(SP) 60th Artillery with attached Battery E (MG), 41st Artillery, remained assigned to I Field Force Vietnam, attached to I ...Battalion (AW)(SP), 60th Artillery, with attached Battery E (MG), 41st Artillery, was detached from 41st Artillery Group and fully attached to I Field Force...States and Free World Military Assistance Forces throughout the II Corps Tactical Zone and the I Corps Tactical Zone.

  20. SPI Observations of Positron Annihilation Radiation from the 4th Galactic Quadrant: Sky Distribution

    NASA Astrophysics Data System (ADS)

    Weidenspointner, G.; Lonjou, V.; Knödlseder, J.; Jean, P.; Allain, M.; von Ballmoos, P.; Harris, M. J.; Vedrenne, G.; Teegarden, B. J.; Gehrels, N.; Guessoum, N.; Schönfelder, V.; Chapuis, C.; Durouchoux, Ph.; Cisana, E.; Valsesia, M.

    2004-10-01

    During its first year in orbit the INTEGRAL observatory performed deep exposures of the Galactic Center region and scanning observations of the Galactic plane. We report on the status of our analysis of the positron annihilation radiation from the 4th Galactic quadrant with the spectrometer SPI, focusing on the sky distribution of the 511 keV line emission. The analysis methods are described; current constraints and limits on the Galactic bulge emission and the bulge-to-disk ratio are presented.

  1. 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

  2. 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.

  3. Interactions of a non-fluorescent fluoroquinolone with biological membrane models: A multi-technique approach.

    PubMed

    Sousa, Carla F; Ferreira, Mariana; Abreu, Bárbara; Medforth, Craig J; Gameiro, Paula

    2015-11-30

    Fluoroquinolones are antibiotics which act by penetrating into bacterial cells and inhibiting enzymes related to DNA replication, and metal complexes of these drugs have recently been investigated as one approach to counteracting bacterial resistance. In this work, we apply a multi-technique approach to studying the partition coefficient (Kp) for the non-fluorescent third-generation fluoroquinolone sparfloxacin or its copper-complex with lipid membrane models of Gram-negative bacteria. The techniques investigated are UV-vis absorption and (19)F NMR spectroscopies together with quenching of a fluorescent probe present in the lipids (using steady-state and time-resolved methods). (19)F NMR spectroscopy has previously been used to determine the Kp values of fluorinated drugs but in the case of sparfloxacin did not yield useful data. However, similar Kp values for sparfloxacin or its copper-complex were obtained for the absorption and fluorescence quenching methods confirming the usefulness of a multi-technique approach. The Kp values measured for sparfloxacin were significantly higher than those found for other fluoroquinolones. In addition, similar Kp values were found for sparfloxacin and copper-complex suggesting that in contrast to other fluoroquinolones hydrophobic diffusion occurs readily for both of these molecules. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. [Pharmacodynamic and pharmacokinetic evaluation of respiratory fluoroquinolones. Guideline to selection of the most appropriate fluoroquinolone].

    PubMed

    Parra-Ruiz, Jorge; Hernández-Quero, José

    2012-12-01

    Since its approval, fluoroquinolones have become one of the most prescribed antibacterial agents. Because of its widespread use, serious concerns about the emergence of resistance in Streptococcus pneumoniae, Pseudomonas spp, and entrobacteriaceae, has arisen, especially because of cross-resistance between fluoroquinolones. Huge efforts has been done to identify pharmacokinetic (PK) parameters like maximum serum concentration (Cmax), area under the curve of serum concentrations (AUC) and pharmacodynamic (PD) parameters like the minimum inhibitory concentration (MIC) or the mutant prevention concentration (MPC), to optimize the use of the new fluoroquinolones, especially against these difficult to treat microorganisms. The new fluoroquinolones commercially available in Spain, levofloxacin and moxifloxacin, have significant differences in their PK (Cmax, half-life, volume of distribution, etc), PD (MIC, MPC,) and in their PK/PD parameters (AUC/MIC; AUC/MPC) that allow clinicians to establish clear preference for the utilization of one of them. Proper use of these new fluoroquinolones according to these PK/PD parameters will result in better management of respiratory infections with a reduction in the emergence of resistance. Based on data reviewed in this paper moxifloxacin use, with best PK/PD characteristics, should be preferred over levofloxacin. Should levofloxacin be used, alternative dosing strategies would be recommended to avoid selection of resistant variants.

  5. 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 4th...

  6. 78 FR 23866 - Safety Zone; Crescent City 4th of July Fireworks; Crescent City Harbor, Crescent City, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-23

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Crescent City 4th of July Fireworks; Crescent City Harbor, Crescent City, CA AGENCY: Coast Guard, DHS. ACTION: Notice of proposed rulemaking... Crescent City, CA in support of the Crescent City 4th of July Fireworks on July 4, 2013. This safety...

  7. 78 FR 23869 - Safety Zone; Redwood City 4th of July Fireworks Show; Port of Redwood City, Redwood City, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-23

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Redwood City 4th of July Fireworks Show; Port of Redwood City, Redwood City, CA AGENCY: Coast Guard, DHS. ACTION: Notice of proposed rulemaking... of Redwood City near Redwood City, CA in support of the Redwood City 4th of July Fireworks Show...

  8. Integrating fluoroquinolones into the hospital formulary.

    PubMed

    Bertino, J S

    2001-10-01

    With the increasing availability of new agents, selection of fluoroquinolones for formulary inclusion can be difficult. Appropriate evaluation of the important characteristics (pharmacokinetic and pharmacodynamic properties, antimicrobial activity, efficacy, tolerability, cost) of these agents should allow selection of the most cost-effective ones. Evidence from in vitro studies and clinical trials indicates differences exist among fluoroquinolones, especially in terms of activity against gram-positive, aerobic organisms. For selected clinical situations, it may be important to choose an agent that is available in both intravenous and oral formulations. Comparative drug costs, as well as costs associated with potential clinical failure and adverse events, should be evaluated carefully. Dosage regimens should be considered, as shorter durations of therapy and less frequent dose administration may lead to reduced labor costs and increased patient compliance, thereby improving effectiveness and economic efficiency.

  9. Protection against Lipopolysaccharide-Induced Death by Fluoroquinolones

    PubMed Central

    Khan, Anis A.; Slifer, Teri R.; Araujo, Fausto G.; Suzuki, Yasuhiro; Remington, Jack S.

    2000-01-01

    Because fluoroquinolones have an immunomodulatory effect on cytokine production by lipopolysaccharide (LPS)-treated human monocytes, we examined the effect of fluoroquinolones on the survival of mice injected with a lethal dose of LPS. Trovafloxacin (100 mg/kg), ciprofloxacin (250 mg/kg), and tosufloxacin (100 mg/kg) protected 75% (P = 0.0001), 25% (P = 0.002), and 50% (P = 0.002), respectively, of mice against death. The fluoroquinolones significantly reduced serum levels of interleukin-6 and tumor necrosis factor alpha in LPS-treated mice. The protective effects of fluoroquinolones in LPS-induced shock in mice may also occur in humans. PMID:11036044

  10. 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

  11. Fluoroquinolone resistance in ophthalmology and the potential role for newer ophthalmic fluoroquinolones.

    PubMed

    Hwang, David G

    2004-03-01

    The three topical ophthalmic fluoroquinolones recently introduced into the U.S. market--levofloxacin, gatifloxacin, and moxifloxacin--offer several advantages over the previously available fluoroquinolones (norfloxacin 0.3%, ciprofloxacin 0.3%, and ofloxacin 0.3%). These include enhanced spectrum and potency for Gram-positive cocci and possibly atypical mycobacterial species, improved penetration into the anterior segment, and reduced propensity to promote the development of resistance. Although published data and clinical experience with these agents is quite limited given their relatively recent entry into the U.S. market, this perspective will attempt to provide an understanding of the potential role of these newer fluorquinolones in addressing the problem of increasing fluoroquinolone resistance amongst bacterial ocular isolates.

  12. 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.

  13. Efficient Recovery of Fluoroquinolone-Susceptible and Fluoroquinolone-Resistant Escherichia coli Strains From Frozen Samples

    PubMed Central

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

    2010-01-01

    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. 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.

  15. [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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 4TH Mediterranean Workshop and Tropical Meeting "Novel Optical Materials and Applications" NOMA 99.

    DTIC Science & Technology

    1999-07-19

    ABSTRACT UNCLASSIFIED UNCLASSIFIED UNCLASSIFIED UL NSN 7540-01-280-5500 Standard Form 298 (Rev. 2-89) Prescribed by ANSI Std. 239-18 298-102 4th...point of view. We use a statistical approach for the nematic order including surface anisotropy in the frame of mean field theory. It gives a Boltzmann...500 pm thick. The crystals, which had damage thresholds > 400 GW/cm2 for 100 fsec pulses at 1600 nm were investigated with open and closed aperture

  1. 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.

  2. The Persistence of Fluoroquinolone-Resistant Campylobacter in Poultry Production

    PubMed Central

    Price, Lance B.; Lackey, Leila G.; Vailes, Rocio; Silbergeld, Ellen

    2007-01-01

    Background The use of antibiotics in food animal production has been associated with antibiotic-resistant infections in humans. In 2005, the Food and Drug Administration (FDA) banned fluoroquinolone use in U.S. poultry production in order to reduce the prevalence of fluoroquinolone-resistant Campylobacter. Little is known about the potential efficacy of this policy. Objectives Our primary objective was to follow temporal changes in the prevalence of fluoroquinolone-resistant Campylobacter among poultry products from two conventional producers who announced their cessation of fluoroquinolone use in 2002 (3 years before the FDA’s ban). Our secondary objective was to compare, over time, the prevalence of fluoroquinolone-resistant Campylobacter in conventional poultry products to those from producers who claim to use no antibiotics. Methods We collected poultry samples from two conventional producers and three antibiotic-free producers over the course of 20 weeks in 2004 (n = 198) and 15 weeks in 2006 (n = 210). We compared the rates of fluoroquinolone resistance among Campylobacter isolates from the different producers. Results We found no significant change in the proportion of fluoroquinolone-resistant Campylobacter isolates from the two conventional producers over the study period. In addition, Campylobacter strains from the two conventional producers were significantly more likely to be fluoroquinolone resistant than those from the antibiotic-free producers. Conclusions The results from this study indicate that fluoroquinolone-resistant Campylobacter may be persistent contaminants of poultry products even after on-farm fluoroquinolone use has ceased. The FDA’s ban on fluoroquinolones in poultry production may be insufficient to reduce resistant Campylobacter in poultry products. PMID:17637919

  3. 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

  4. Beliefs about the causes of obesity in a national sample of 4th year medical students.

    PubMed

    Phelan, Sean M; Burgess, Diana J; Burke, Sara E; Przedworski, Julia M; Dovidio, John F; Hardeman, Rachel; Morris, Megan; van Ryn, Michelle

    2015-11-01

    Physician knowledge of the complex contributors to obesity varies. We do not know whether today's medical students are graduating with deep understanding of the causes of obesity. Our objective was to assess beliefs about causes of obesity in a national sample of 4th year medical students. We randomly selected 2000 4th year students from a random sample of 50 U.S. medical schools and asked them to rate the importance of several factors as causes of obesity. Of those invited, 1244 (62%) responded. We conducted latent class analysis to identify groups with similar response patterns. Most students demonstrated knowledge that obesity has multiple contributors. Students fell into 1 of 4 classes: (1) more likely to endorse all contributors (28%), (2) more likely to endorse physiological contributors (27%), (3) more likely to endorse behavioral or social contributors (24%), and (4) unlikely to endorse contributors outside of overeating and physical activity (22%). Though students were generally aware of multiple causes, there were 4 distinct patterns of beliefs, with implications for patient care. Targeted interventions may help to improve depth of knowledge about the causes of obesity and lead to more effective care for obese patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. 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.

  6. 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.

  7. 2nd to 4th digit ratios, fetal testosterone and estradiol.

    PubMed

    Lutchmaya, S; Baron-Cohen, S; Raggatt, P; Knickmeyer, R; Manning, J T

    2004-04-01

    The ratio of 2nd to 4th digit length (2D:4D) is sexually dimorphic (mean 2D:4D is lower in males than females) and is thought to be fixed early in development. 2D:4D has been reported to be related to fetal growth, hand preference, autism, Asperger's syndrome, sperm counts, family size, age at myocardial infarction in men and breast cancer in women. There is indirect evidence that 2D:4D is established in utero and is negatively related to prenatal testosterone and positively with prenatal estradiol. However, there are no studies which show direct relationships between fetal testosterone (FT), fetal estradiol (FE) and 2D:4D. To investigate the relationships between 2D:4D ratios and FT and FE from amniotic fluid. Cohort study. 33 children. Radioimmunoassays of FT and FE obtained from routine amniocentesis; 2D:4D ratios calculated from 2nd and 4th digit length of the right and left hands at age 2 years. A significant negative association between right 2D:4D ratio and FT/FE ratio, which was independent of sex. These preliminary findings lend support to an association between low 2D:4D and high levels of FT relative to FE, and high 2D:4D with low FT relative to FE.

  8. Improving the quality of adverse drug reaction reporting by 4th-year medical students.

    PubMed

    Rosebraugh, Curtis J; Tsong, Yi; Zhou, Feng; Chen, Min; Mackey, Ann Corken; Flowers, Charlene; Toyer, Denise; Flockhart, David A; Honig, Peter K

    2003-03-01

    Evaluate whether a 15-minute lecture intervention will improve adverse drug reaction reporting quality on standard MedWatch forms. Seventy-eight 4th-year medical students were randomized to intervention 'Group-A' or non-intervention 'Group-B' on the first day of a required five-day clinical pharmacology rotation. Group-A participants attended a 15-minute lecture on completing a MedWatch form with quality information considered by the Food and Drug Administration as critical to adequate adverse drug reaction reporting. Group-B participants did not attend this lecture. Both groups then watched a standardized patient interview of a recognizable adverse drug reaction and completed MedWatch forms. Four Safety Evaluators from the Food and Drug Administration (FDA) rated student responses in a blinded fashion for the primary efficacy variable of Overall Impression and six informational domins using a standardized data quality analysis form that was developed within the Office of Postmarketing Drug Risk Assessment of the FDA. Seventy-eight MedWatch forms were evaluated (Group-A = 40, Group B = 38). Overall MedWatch information quality scores for the intervention group were significantly higher than the non-intervention group (p < 0.004). As little as a 15-minute intervention can significantly improve the quality of adverse drug reaction reporting by 4th-year medical students. Academic medical centers should consider incorporating adverse drug reaction reporting curriculum into the clinical training of medical students.

  9. 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

  10. Crime rates and sedentary behavior among 4th grade Texas school children.

    PubMed

    Brown, H Shelton; Pérez, Adriana; Mirchandani, Gita G; Hoelscher, Deanna M; Kelder, Steven H

    2008-05-14

    Although per capita crime has generally fallen over the period which coincides with the obesity epidemic, it has not fallen uniformly across communities. It also has not fallen enough to allay fears on the part of parents. Over the past 30 years, technological changes have made the indoor alternatives to playing outside, where children are more vulnerable to criminal activity, more enjoyable (cable TV, video games, and the internet) and comfortable (the spread of air conditioning to low income neighborhoods). We determined whether indoor sedentary behavior patterns are associated with community crime statistics. 4th graders in the U.S. are typically 9 or 10 years old. We used data from the 2004-2005 Texas School Physical Activity and Nutrition (SPAN) survey linked with U.S. Department of Justice, Office of Justice Programs, Bureau of Justice Statistics data for the years 2000 through 2005 and Texas State data on sexual offenders. The probability-based sample included a total of 7,907 children in grade four. Multistage probability sampling weights were used. The dependent variables included were hours of TV watching, video game playing, computer use and total indoor sedentary behavior after school. Incremental Relative Rates were computed for community crime rates including robberies, all violent crimes, murders, assaults, property crimes, rapes, burglaries, larcenies and motor vehicle thefts as well as for sexual offenders living in the neighborhood. The neighborhood refers to the areas where the students at each school live. In the case of sexual offenders, sexual offenders per capita are estimated using the per capita rate in the zip code of the school attended; all other crime statistics are estimated by the crimes per capita in the police department jurisdiction covering the school attended. After controlling for sex, age, and African-American and Hispanic, cross-sectional associations were determined using multivariate Poisson regression. 4th grade boys were

  11. 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

  12. Safety profile of the respiratory fluoroquinolone moxifloxacin: comparison with other fluoroquinolones and other antibacterial classes.

    PubMed

    Van Bambeke, Françoise; Tulkens, Paul M

    2009-01-01

    Moxifloxacin, a fluoroquinolone with potent activity against respiratory pathogens, is approved and considered as an alternative to beta-lactams and macrolides for the treatment of acute bacterial sinusitis and lower respiratory tract infections. In this review, we critically examine its safety profile in comparison with other fluoroquinolones and other antibacterial classes sharing similar indications. Data were extracted from published clinical trials, meta-analyses, postmarketing studies, spontaneous report systems and case reports for rare effects. Global analysis did not reveal significantly higher incidences of drug-related adverse effects than for comparators. Tendon rupture was infrequent with moxifloxacin, including when used in elderly patients with chronic obstructive pulmonary disease. Severe toxic cutaneous reactions and allergies were very rare. Phototoxicity and CNS adverse effects were less common than with other fluoroquinolones. Although causing a 4-7 msec corrected QT interval prolongation, severe cardiac toxicity was neither seen in large cohorts or clinical trials nor reported to pharmacovigilance systems. Hepatotoxicity was not different from what was observed for other fluoroquinolones (excluding trovafloxacin) and less frequent than reported for amoxicillin-clavulanic acid or telithromycin. The data show that using moxifloxacin, in its accepted indications and following the corresponding guidelines, should not be associated with an excessive incidence of drug-related adverse reactions, provided the clinician takes care in identifying patients with known risk factors and pays due attention to the contraindications and warnings mentioned in the labelling.

  13. Risk factors for fluoroquinolone resistance in ocular cultures.

    PubMed

    Lee, Junsung; Choi, Sangkyung

    2015-02-01

    To identify the risk factors associated with fluoroquinolone resistance in patients undergoing cataract surgery. A total of 1,125 patients (1,125 eyes) who underwent cataract surgery at Veterans Health Service Medical Center from May 2011 to July 2012 were enrolled in this study. Conjunctival cultures were obtained from the patients on the day of surgery before instillation of any ophthalmic solutions. The medical records of patients with positive coagulase negative staphylococcus (CNS) and Staphylococcus aureus (S. aureus) cultures were reviewed to determine factors associated with fluoroquinolone resistance. Of 734 CNS and S. aureus cultures, 175 (23.8%) were resistant to ciprofloxacin, levofloxacin, gatifloxacin, or moxifloxacin. Use of fluoroquinolone within 3 months and within 1 year before surgery, topical antibiotic use other than fluoroquinolone, systemic antibiotic use, recent hospitalization, ocular surgery, intravitreal injection and use of eyedrops containing benzalkonium chloride were significantly more frequent in resistant isolates than in susceptible isolates. In multivariable logistic regression analysis, ocular surgery (odds ratio [OR], 8.457), recent hospitalization (OR, 6.646) and use of fluoroquinolone within 3 months before surgery (OR, 4.918) were significant predictors of fluoroquinolone resistance, along with intravitreal injection (OR, 2.976), systemic antibiotic use (OR, 2.665), use of eyedrops containing benzalkonium chloride (OR, 2.323), use of fluoroquinolone within 1 year before surgery (OR, 1.943) and topical antibiotic use other than fluoroquinolone (OR, 1.673). Recent topical fluoroquinolone use, hospitalization and ocular surgery were significantly associated with fluoroquinolone resistance in CNS and S. aureus isolates from ocular culture.

  14. Risk Factors for Fluoroquinolone Resistance in Ocular Cultures

    PubMed Central

    Lee, Junsung

    2015-01-01

    Purpose To identify the risk factors associated with fluoroquinolone resistance in patients undergoing cataract surgery. Methods A total of 1,125 patients (1,125 eyes) who underwent cataract surgery at Veterans Health Service Medical Center from May 2011 to July 2012 were enrolled in this study. Conjunctival cultures were obtained from the patients on the day of surgery before instillation of any ophthalmic solutions. The medical records of patients with positive coagulase negative staphylococcus (CNS) and Staphylococcus aureus (S. aureus) cultures were reviewed to determine factors associated with fluoroquinolone resistance. Results Of 734 CNS and S. aureus cultures, 175 (23.8%) were resistant to ciprofloxacin, levofloxacin, gatifloxacin, or moxifloxacin. Use of fluoroquinolone within 3 months and within 1 year before surgery, topical antibiotic use other than fluoroquinolone, systemic antibiotic use, recent hospitalization, ocular surgery, intravitreal injection and use of eyedrops containing benzalkonium chloride were significantly more frequent in resistant isolates than in susceptible isolates. In multivariable logistic regression analysis, ocular surgery (odds ratio [OR], 8.457), recent hospitalization (OR, 6.646) and use of fluoroquinolone within 3 months before surgery (OR, 4.918) were significant predictors of fluoroquinolone resistance, along with intravitreal injection (OR, 2.976), systemic antibiotic use (OR, 2.665), use of eyedrops containing benzalkonium chloride (OR, 2.323), use of fluoroquinolone within 1 year before surgery (OR, 1.943) and topical antibiotic use other than fluoroquinolone (OR, 1.673). Conclusions Recent topical fluoroquinolone use, hospitalization and ocular surgery were significantly associated with fluoroquinolone resistance in CNS and S. aureus isolates from ocular culture. PMID:25646055

  15. Fluoroquinolones for the treatment of tuberculosis in children.

    PubMed

    Thee, S; Garcia-Prats, A J; Donald, P R; Hesseling, A C; Schaaf, H S

    2015-05-01

    The fluoroquinolones are key components of current multidrug-resistant tuberculosis (MDR-TB) treatment regimens and are being evaluated in shortened treatment regimens as well as in the prevention of drug-resistant TB. The objective of this review was to identify existing evidence for the use of the fluoroquinolones ofloxacin, levofloxacin and moxifloxacin in the treatment of TB in children. Existing data from in vitro, animal and human studies consistently demonstrate the efficacy of the fluoroquinolones against Mycobacterium tuberculosis, with superiority of levofloxacin and moxifloxacin compared to ofloxacin. In vitro and murine studies demonstrated the potential of moxifloxacin to shorten drug-susceptible TB treatment, but in multiple randomized controlled trials shortened fluoroquinolone-containing regimens have not been non-inferior compared to standard therapy. Resistance occurs frequently via mutations in the gyrA gene, and emerges rapidly depending on the fluoroquinolone concentration, with newer more potent fluoroquinolones less likely to develop resistance. Emerging data from paediatric studies underlines the importance of fluoroquinolones in the treatment of MDR-TB in children. There is a paucity of pharmacokinetic data especially in children <5 years of age and HIV-infected children; existing studies show substantially lower serum concentrations in children compared to adults at currently recommended doses, probably due to faster elimination. This has implications for optimizing paediatric treatment and for the development of resistance. Fluoroquinolone use has been restricted in children due to concerns about drug-induced arthropathy. The available data does not demonstrate any serious arthropathy or other severe toxicity in children. Although there is limited paediatric safety data for the prolonged treatment of MDR-TB, extended administration of fluoroquinolones in adults with MDR-TB does not show serious adverse effects and there is no evidence

  16. Fluoroquinolone-resistant Campylobacter species and the withdrawal of fluoroquinolones from use in poultry: a public health success story.

    PubMed

    Nelson, Jennifer M; Chiller, Tom M; Powers, John H; Angulo, Frederick J

    2007-04-01

    Campylobacter species cause 1.4 million infections each year in the United States. Fluoroquinolones (e.g., ciprofloxacin) are commonly used in adults with Campylobacter infection and other infections. Fluoroquinolones (e.g., enrofloxacin) are also used in veterinary medicine. Human infections with fluoroquinolone-resistant Campylobacter species have become increasingly common and are associated with consumption of poultry. These findings, along with other data, prompted the US Food and Drug Administration to propose the withdrawal of fluoroquinolone use in poultry in 2000. A lengthy legal hearing concluded with an order to withdraw enrofloxacin from use in poultry (effective in September 2005). Clinicians are likely to continue to encounter patients with fluoroquinolone-resistant Campylobacter infection and other enteric infection because of the continued circulation of fluoroquinolone-resistant Campylobacter species in poultry flocks and in persons returning from foreign travel who have acquired a fluoroquinolone-resistant enteric infection while abroad. Judicious use of fluoroquinolones and other antimicrobial agents in human and veterinary medicine is essential to preserve the efficacy of these important chemotherapeutic agents.

  17. Identification of 4th intercostal space using sternal notch to xiphoid length for accurate electrocardiogram lead placement.

    PubMed

    Day, Kevin; Oliva, Isabel; Krupinski, Elizabeth; Marcus, Frank

    2015-01-01

    Precordial ECG lead placement is difficult in obese patients with increased chest wall soft tissues due to inaccurate palpation of the intercostal spaces. We investigated whether the length of the sternum (distance between the sternal notch and xiphoid process) can accurately predict the location of the 4th intercostal space, which is the traditional location for V1 lead position. Fifty-five consecutive adult chest computed tomography examinations were reviewed for measurements. The sternal notch to right 4th intercostal space distance was 67% of the sternal notch to xiphoid process length with an overall correlation of r=0.600 (p<0.001). The above measurement may be utilized to locate the 4th intercostal space for accurate placement of the precordial electrodes in adults in whom the 4th intercostal space cannot be found by physical exam. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Fluoroquinolone-resistant mutants of Burkholderia cepacia.

    PubMed

    Pope, C F; Gillespie, S H; Pratten, J R; McHugh, T D

    2008-03-01

    Fluoroquinolone-resistant Burkholderia cepacia mutants were selected on ciprofloxacin. The rate of mutation in gyrA was estimated to be 9.6 x 10(-11) mutations per division. Mutations in gyrA conferred 12- to 64-fold increases in MIC, and an additional parC mutation conferred a large increase in MIC (>256-fold). Growth rate, biofilm formation, and survival in water and during drying were not impaired in strains containing single gyrA mutations. Double mutants were impaired only in growth rate (0.85, relative to the susceptible parent).

  19. [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.

  20. 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

    2017-01-01

    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.

  1. 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

  2. STO-2: Support for 4th Year Operations, Recovery, and Science ASU Co-I

    NASA Astrophysics Data System (ADS)

    Groppi, Christopher

    This is a Co-Investigator proposal for "STO-2: Support for 4th Year Operations, Recovery, and Science" with Prof. Christopher K. Walker (University of Arizona) as PI. As a participant in the STO-2 mission, ASU will participate in instrument design and construction, mission I&T, flight operations and data analysis. ASU has unique capabilities in the field of direct metal micromachining, which it will bring to bear on the STO-2 cold optical assembly, flight mixers and LO hardware. In addition, our extensive experience with receiver integration and test will supplement the capabilities of the PI institution during the I&T phase at the University of Arizona, CSBF (Palestine, TX) and in Antarctica. Both the ASU PI and student will also participate in data analysis and publication after the flight.

  3. Giant viruses in the oceans: the 4th Algal Virus Workshop.

    PubMed

    Claverie, Jean-Michel

    2005-06-20

    Giant double-stranded DNA viruses (such as record breaking Acanthamoeba polyphaga Mimivirus), with particle sizes of 0.2 to 0.6 microm, genomes of 300 kbp to 1.200 kbp, and commensurate complex gene contents, constitute an evolutionary mystery. They challenge the common vision of viruses, traditionally seen as highly streamlined genomes optimally fitted to the smallest possible--filterable--package. Such giant viruses are now discovered in increasing numbers through the systematic sampling of ocean waters as well as freshwater aquatic environments, where they play a significant role in controlling phyto- and bacterio- plankton populations. The 4th Algal Virus Workshop showed that the study of these ecologically important viruses is now massively entering the genomic era, promising a better understanding of their diversity and, hopefully, some insights on their origin and the evolutionary forces that shaped their genomes.

  4. Idaho National Laboratory Quarterly Occurrence Analysis 4th Quarter FY 2016

    SciTech Connect

    Mitchell, Lisbeth Ann

    2016-11-01

    This report is published quarterly by the Idaho National Laboratory (INL) Quality and Performance Management Organization. The Department of Energy (DOE) Occurrence Reporting and Processing System, as prescribed in DOE Order 232.2, “Occurrence Reporting and Processing of Operations Information,” requires a quarterly analysis of events, both reportable and not reportable, for the previous 12 months. This report is the analysis of 84 reportable events (29 from the 4th quarter fiscal year 2016 and 55 from the prior three reporting quarters), as well as 39 other issue reports (including events found to be not reportable and Significant Category A and B conditions) identified at INL during the past 12 months (two from this quarter and 37 from the prior three quarters).

  5. Cage Regional Energy Budgets from the GLAS 4TH Order Model

    NASA Technical Reports Server (NTRS)

    Herman, G. F.; Alexder, M. A.; Shubert, S. D.

    1984-01-01

    The status and future plans of a study to (1) assess the accuracy of regional energy balance calculations obtained from the 4th-order model, (2) determine the impact of satellite data on the calculations, and (3) determine their utility for ocean energy transport studies are discussed. An equation is presented which models the vertically-integrated, time and areally-averaged total energy content of a region of the atmosphere extending from the surface to the top of the atmosphere. All of the terms of the equation were evaluated using early versions of the GLAS FGGE IIIb analysis, and analysis with satellite data deleted. Results show that the budget is dominated by the surface fluxes, net radiation, and horizontal atmospoheric divergence.

  6. The 4th Bologna Winter School: Hot Topics in Structural Genomics

    PubMed Central

    2003-01-01

    The 4th Bologna Winter School on Biotechnologies was held on 9–15 February 2003 at the University of Bologna, Italy, with the specific aim of discussing recent developments in bioinformatics. The school provided an opportunity for students and scientists to debate current problems in computational biology and possible solutions. The course, co-supported (as last year) by the European Science Foundation program on Functional Genomics, focused mainly on hot topics in structural genomics, including recent CASP and CAPRI results, recent and promising genomewide predictions, protein–protein and protein–DNA interaction predictions and genome functional annotation. The topics were organized into four main sections (http://www.biocomp.unibo.it). PMID:18629078

  7. Increased ratio of 2nd to 4th digit (2D:4D) in schizophrenia.

    PubMed

    Collinson, Simon Lowes; Lim, Matthew; Chaw, Jia Hui; Verma, Swapna; Sim, Kang; Rapisarda, Attilio; Chong, Siow Ann

    2010-03-30

    Sex differences in the onset, epidemiology, clinical presentation and neuropathology of schizophrenia suggest that sexual dimorphism in brain development may be relevant to pathogenesis. Sex hormones, in particular testosterone, are considered to be crucial in brain development, but few investigations have examined the potential role of prenatal testosterone in schizophrenia. In this study, we examined a retrospective marker of prenatal testosterone release - 2D:4D finger length ratio (2D:4D), the relative length of 2nd to 4th digit, in 64 Asian patients with schizophrenia and 64 sex-matched controls. No significant difference in mean finger lengths was present, however 2D:4D ratio was significantly different between patients and controls. The effect was primarily seen in males consistent with a 'less masculinised' pattern and hypotheses suggesting that schizophrenia may be associated with an abnormality in prenatal circulating testosterone. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  8. 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.

  9. 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; hide

    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.

  10. 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.

  11. 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

  12. 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.

  13. Mechanisms of clinical resistance to fluoroquinolones in Enterococcus faecalis.

    PubMed Central

    Nakanishi, N; Yoshida, S; Wakebe, H; Inoue, M; Mitsuhashi, S

    1991-01-01

    About 10% of 100 clinical isolates of Enterococcus faecalis were resistant to greater than or equal to 25 micrograms of norfloxacin, ofloxacin, ciprofloxacin, and temafloxacin per ml. In this study, the DNA gyrase of E. faecalis was purified from a fluoroquinolone-susceptible strain (ATCC 19433) and two resistant isolates, MS16968 and MS16996. Strains MS16968 and MS16996 were 64- to 128-fold and 16- to 32-fold less susceptible, respectively, to fluoroquinolones than was ATCC 19433; MICs of nonquinolone antibacterial agents for these strains were almost equal. The DNA gyrase from ATCC 19433 had two subunits, designated A and B, with properties similar to those of DNA gyrase from other gram-positive bacteria such as Bacillus subtilis and Micrococcus luteus. Inhibition of the supercoiling activity of the enzyme from ATCC 19433 by the fluoroquinolones correlated with their antibacterial activities. In contrast, preparations of DNA gyrase from MS16968 and MS16996 were at least 30-fold less sensitive to inhibition of supercoiling by the fluoroquinolones than the gyrase from ATCC 19433 was. Experiments that combined heterologous gyrase subunits showed that the A subunit from either of the resistant isolates conferred resistance to fluoroquinolones. These findings indicate that an alteration in the gyrase A subunit is the major contributor to fluoroquinolone resistance in E. faecalis clinical isolates. A difference in drug uptake may also contribute to the level of fluoroquinolone resistance in these isolates. Images PMID:1656852

  14. Unnecessary use of fluoroquinolone antibiotics in hospitalized patients.

    PubMed

    Werner, Nicole L; Hecker, Michelle T; Sethi, Ajay K; Donskey, Curtis J

    2011-07-05

    Fluoroquinolones are among the most commonly prescribed antimicrobials and are an important risk factor for colonization and infection with fluoroquinolone-resistant gram-negative bacilli and for Clostridium difficile infection (CDI). In this study, our aim was to determine current patterns of inappropriate fluoroquinolone prescribing among hospitalized patients, and to test the hypothesis that longer than necessary treatment durations account for a significant proportion of unnecessary fluoroquinolone use. We conducted a 6-week prospective, observational study to determine the frequency of, reasons for, and adverse effects associated with unnecessary fluoroquinolone use in a tertiary-care academic medical center. For randomly-selected adult inpatients receiving fluoroquinolones, therapy was determined to be necessary or unnecessary based on published guidelines or standard principles of infectious diseases. Adverse effects were determined based on chart review 6 weeks after completion of therapy. Of 1,773 days of fluoroquinolone therapy, 690 (39%) were deemed unnecessary. The most common reasons for unnecessary therapy included administration of antimicrobials for non-infectious or non-bacterial syndromes (292 days-of-therapy) and administration of antimicrobials for longer than necessary durations (234 days-of-therapy). The most common syndrome associated with unnecessary therapy was urinary tract infection or asymptomatic bacteriuria (30% of all unnecessary days-of-therapy). Twenty-seven percent (60/227) of regimens were associated with adverse effects possibly attributable to therapy, including gastrointestinal adverse effects (14% of regimens), colonization by resistant pathogens (8% of regimens), and CDI (4% of regimens). In our institution, 39% of all days of fluoroquinolone therapy were unnecessary. Interventions that focus on improving adherence with current guidelines for duration of antimicrobial therapy and for management of urinary syndromes could

  15. Unnecessary use of fluoroquinolone antibiotics in hospitalized patients

    PubMed Central

    2011-01-01

    Background Fluoroquinolones are among the most commonly prescribed antimicrobials and are an important risk factor for colonization and infection with fluoroquinolone-resistant gram-negative bacilli and for Clostridium difficile infection (CDI). In this study, our aim was to determine current patterns of inappropriate fluoroquinolone prescribing among hospitalized patients, and to test the hypothesis that longer than necessary treatment durations account for a significant proportion of unnecessary fluoroquinolone use. Methods We conducted a 6-week prospective, observational study to determine the frequency of, reasons for, and adverse effects associated with unnecessary fluoroquinolone use in a tertiary-care academic medical center. For randomly-selected adult inpatients receiving fluoroquinolones, therapy was determined to be necessary or unnecessary based on published guidelines or standard principles of infectious diseases. Adverse effects were determined based on chart review 6 weeks after completion of therapy. Results Of 1,773 days of fluoroquinolone therapy, 690 (39%) were deemed unnecessary. The most common reasons for unnecessary therapy included administration of antimicrobials for non-infectious or non-bacterial syndromes (292 days-of-therapy) and administration of antimicrobials for longer than necessary durations (234 days-of-therapy). The most common syndrome associated with unnecessary therapy was urinary tract infection or asymptomatic bacteriuria (30% of all unnecessary days-of-therapy). Twenty-seven percent (60/227) of regimens were associated with adverse effects possibly attributable to therapy, including gastrointestinal adverse effects (14% of regimens), colonization by resistant pathogens (8% of regimens), and CDI (4% of regimens). Conclusions In our institution, 39% of all days of fluoroquinolone therapy were unnecessary. Interventions that focus on improving adherence with current guidelines for duration of antimicrobial therapy and for

  16. Fluoroquinolone resistance during 2000-2005: an observational study.

    PubMed

    Ryan, Richard J; Lindsell, Chris; Sheehan, Paul

    2008-05-24

    Moxifloxacin is a respiratory fluoroquinolone with a community acquired pneumonia indication. Unlike other fluoroquinolones used in our healthcare system, moxifloxacin's urinary excretion is low and thus we hypothesized that increased use of moxifloxacin is associated with an increase in fluoroquinolone resistance amongst gram negative uropathogens. All antibiograms for Gram negative bacteria were obtained for 2000 to 2005. The defined daily dose (DDD) for each fluoroquinolone was computed according to World Health Organization criteria. To account for fluctuation in patient volume, DDD/1000 bed days was computed for each year of study. Association between DDD/1000 bed days for each fluoroquinolone and the susceptibility of Gram negative bacteria to ciprofloxacin was assessed using Pearson's Correlation Coefficient, r. During the study period, there were 48,261 antibiograms, 347,931 DDD of fluoroquinolones, and 1,943,338 bed days. Use of fluoroquinolones among inpatients decreased from 237.2 DDD/1000 bed days in 2000 to 115.2 DDD/1000 bed days in 2005. With the exception of Enterobacter aerogenes, moxifloxacin use was negatively correlated with sensitivity among all 13 Gram negative species evaluated (r = -0.07 to -0.97). When the sensitivities of all Gram negative organisms were aggregated, all fluoroquinolones except moxifloxacin were associated with increased sensitivity (r = 0.486 to 1.000) while moxifloxacin was associated with decreased sensitivity (r = -0.464). Moxifloxacin, while indicated for empiric treatment of community acquired pneumonia, may have important negative influence on local antibiotic sensitivities amongst Gram negative organisms. This effect was not shared by other commonly used members of the fluoroquinolone class.

  17. Fluoroquinolone resistance during 2000–2005 : An observational study

    PubMed Central

    Ryan, Richard J; Lindsell, Chris; Sheehan, Paul

    2008-01-01

    Background Moxifloxacin is a respiratory fluoroquinolone with a community acquired pneumonia indication. Unlike other fluoroquinolones used in our healthcare system, moxifloxacin's urinary excretion is low and thus we hypothesized that increased use of moxifloxacin is associated with an increase in fluoroquinolone resistance amongst gram negative uropathogens. Methods All antibiograms for Gram negative bacteria were obtained for 2000 to 2005. The defined daily dose (DDD) for each fluoroquinolone was computed according to World Health Organization criteria. To account for fluctuation in patient volume, DDD/1000 bed days was computed for each year of study. Association between DDD/1000 bed days for each fluoroquinolone and the susceptibility of Gram negative bacteria to ciprofloxacin was assessed using Pearson's Correlation Coefficient, r. Results During the study period, there were 48,261 antibiograms, 347,931 DDD of fluoroquinolones, and 1,943,338 bed days. Use of fluoroquinolones among inpatients decreased from 237.2 DDD/1000 bed days in 2000 to 115.2 DDD/1000 bed days in 2005. With the exception of Enterobacter aerogenes, moxifloxacin use was negatively correlated with sensitivity among all 13 Gram negative species evaluated (r = -0.07 to -0.97). When the sensitivities of all Gram negative organisms were aggregated, all fluoroquinolones except moxifloxacin were associated with increased sensitivity (r = 0.486 to 1.000) while moxifloxacin was associated with decreased sensitivity (r = -0.464). Conclusion Moxifloxacin, while indicated for empiric treatment of community acquired pneumonia, may have important negative influence on local antibiotic sensitivities amongst Gram negative organisms. This effect was not shared by other commonly used members of the fluoroquinolone class. PMID:18501015

  18. Dramatic decrease in fluoroquinolones in the pediatric population in Korea.

    PubMed

    Shin, Ju-Young; Kim, Mi Hee; Shin, Sun Mi; Lee, Shin Haeng; Park, Byung-Joo

    2014-12-01

    This study was performed to evaluate the change of prescribing patterns after the regulatory action regarding fluoroquinolones in pediatric patients. We conducted a time series analysis using the Korea Health Insurance Review and Assessment Service National Patients Sample database. Study subjects consisted of pediatric patients under 18 years of age who were prescribed antibiotics at least once (ATC code, J01) before (January 2009-December 2009) and after implementation (January 2010-December 2011) of the regulation. The use of fluoroquinolones was defined as the use of the following antibiotics for at least once in pediatric patients: ofloxacin, ciprofloxacin, norfloxacin, lomefloxacin, levofloxacin, and gemifloxacin. We calculated the number of pediatric fluoroquinolone users for each month. The difference between proportions before and after the regulation was estimated as relative and absolute reduction of fluoroquinolone use. We calculated 95% confidence intervals (CI). We identified 4, 945, 169 antibiotic prescriptions in 484, 914 pediatric patients. During the 12-month period before implementation, percentage of fluoroquinolone use was 4.81% (95% CI: 4.70-4.91%, N = 8001). We observed a rapid decrease in the monthly number of fluoroquinolone users in pediatric population after the implementation of regulatory action. In the year after regulatory action, the percentage of fluoroquinolone use was only 0.26% (95% CI: 0.24-0.28%, N = 834). Overall, there was a 94.55% relative reduction (95% CI: 88.02-101.56%) in the use of fluoroquinolones. Korean regulatory actions regarding fluoroquinolones had an effect of reducing use in pediatric population. Copyright © 2014 John Wiley & Sons, Ltd.

  19. Hypersensitivity reactions to fluoroquinolones: analysis of the factors involved.

    PubMed

    Blanca-López, N; Ariza, A; Doña, I; Mayorga, C; Montañez, M I; Garcia-Campos, J; Gomez, F; Rondón, C; Blanca, M; Torres, M J

    2013-05-01

    Hypersensitivity reactions to fluoroquinolones seem to be on the increase, especially immediate type reactions. The aim of this study was to determine whether several conditions, including gender, age, type of reaction, time interval between the reaction and the study, type of symptoms, the specific fluoroquinolone involved in the reaction and previous confirmed hypersensitivity to betalactams or to other drugs were factors contributing to the development of hypersensitivity to fluoroquinolones. We analysed retrospectively all patients attending our allergy department between January 2005 and December 2010 because of a reaction associated with fluoroquinolone administration. The diagnosis was confirmed by basophil activation test or drug provocation tests. In accordance with the results, patients were then classified as having hypersensitivity or non-hypersensitivity to fluoroquinolones. A group of 218 patients was evaluated; 69 were confirmed as having hypersensitivity, 146 as non-hypersensitivity and 3 were excluded. Comparisons between groups showed that the allergic patients more often had a previous confirmed hypersensitivity to betalactams (P = 0.029), immediate reactions (P = 0.001) and anaphylaxis (P = 0.000), and moxifloxacin was the fluoroquinolone most frequently involved (P = 0.027). The logistic regression analysis showed three factors associated with the diagnosis of hypersensitivity reactions to fluoroquinolones: previous hypersensitivity to betalactams (OR: 4.571; 95% CI: 0.987-21.171; adjusted OR: 23.654; 95% CI: 1.529-365.853), immediate reactions (OR: 17.333; 95% CI: 4.374-68.691; adjusted OR: 52.493; 95% CI: 6.621-416.200) and reactions induced by moxifloxacin (OR: 3.091; 95% CI: 1.160-8.239; adjusted OR: 13.610; 95% CI: 2.419-76.565). In patients who develop reactions to fluoroquinolones, hypersensitivity is more often confirmed in those with immediate reactions and when moxifloxacin is involved. Moreover, patients with hypersensitivity to

  20. Fluoroquinolone-Associated Tendinopathy: Does Levofloxacin Pose the Greatest Risk?

    PubMed

    Bidell, Monique R; Lodise, Thomas P

    2016-06-01

    Fluoroquinolone antibiotics recently have gained increased national attention due to safety concerns. A well-described and serious adverse event associated with receipt of fluoroquinolones is tendinitis and tendon rupture. These tendon injuries can result in long-term sequelae, including chronic pain and mobility restrictions, and may warrant surgery. Due to the severity of these adverse events, a black box warning is included in the product labeling of all fluoroquinolones. In light of the mounting concerns surrounding fluoroquinolone-associated toxicities, the purpose of this clinical review is to provide a comprehensive summary of the risk of tendinopathy associated with levofloxacin, one of the most widely prescribed antibiotics in the United States, across in vitro, animal, and clinical studies, relative to other antibiotics. As part of this review, clinical presentation and onset, proposed mechanisms, patient-specific risk factors, and management of fluoroquinolone-induced tendon injury are summarized. Data were obtained from a comprehensive PubMed literature search and a review of U.S. Food and Drug Administration documents. Although tendinopathy is considered a fluoroquinolone class-wide toxicity, data from in vitro studies, animal studies, patient-level analyses, and large national and international surveillance reports suggest that levofloxacin, as well as its parent compound ofloxacin, possess higher propensities to cause tendon damage relative to other fluoroquinolones. Risk with ofloxacin and levofloxacin appears to be exposure dependent, with higher doses and longer durations being most commonly associated with tendinopathy. Other well-described patient risk factors for fluoroquinolone-associated tendinopathy include older age (older than 60 yrs), receipt of concomitant corticosteroid therapy, presence of renal dysfunction, and history of solid organ transplantation. Given widespread use of levofloxacin across patient care settings, knowledge of both

  1. Association Between Oral Fluoroquinolone Use and Retinal Detachment.

    PubMed

    Raguideau, Fanny; Lemaitre, Magali; Dray-Spira, Rosemary; Zureik, Mahmoud

    2016-04-01

    Several studies have focused on the current use of oral fluoroquinolones and the risk for retinal detachment (RD), but the existence of this association is under debate. Given the widespread fluoroquinolone use, investigation of this association is essential. To assess the association between oral fluoroquinolone use and the risk for RD, including the rhegmatogenous and exudative types. This case-crossover study included 27,540 adults with RD from French health care databases from July 1, 2010, through December 31, 2013. Patients with a history of RD or retinal break, endophthalmitis, intravitreal injection, choroidal retinal vitreal biopsy, and human immunodeficiency virus infection or those hospitalized within 6 months of RD were excluded. The risk period of primary interest was current use, defined as exposure to fluoroquinolones within 10 days immediately before RD surgery, according to previous findings. Oral fluoroquinolone use was assumed to start on the day the prescription was dispensed. Exposure to fluoroquinolones during the risk period (1-10 days) compared with the control period (61-180 days). The association was also assessed regarding use in the recent (11-30 days) and past (31-60 days) intermediate risk period, type of fluoroquinolone, and type of RD. Of the 27,540 eligible patients (57% men; mean [SD] age, 61.5 [13.6] years), 663 patients with RD were exposed to fluoroquinolones during the observation period, corresponding to 80 cases exposed during the 10-day risk period (≤10 days before RD) and 583 cases exposed during the control period (61-180 days). We found a significant increased risk for RD during the 10-day period after the dispensing of oral fluoroquinolones, with an adjusted odds ratio of 1.46 (95% CI, 1.15-1.87). The risk was significantly increased for rhegmatogenous and exudative RD, with adjusted odds ratios of 1.41 (95% CI, 1.04-1.92) and 2.57 (95% CI, 1.46-4.53), respectively. Recent and past use of fluoroquinolones were not

  2. Fluoroquinolones in the treatment of bronchopulmonary disease in cystic fibrosis.

    PubMed

    Hurley, Matthew; Smyth, Alan

    2012-12-01

    Fluoroquinolones are commonly used to treat lung infections in patients with cystic fibrosis. These patients are susceptible to lung infection with common bacteria such as Staphylococcus aureus and Haemophilus influenzae, but are also prone to infection by opportunistic bacteria, including Pseudomonas aeruginosa. The good oral bioavailability and broad antimicrobial spectrum of activity, including antipseudomonal properties, make this class of antimicrobial attractive. We review the evidence assessing the use of fluoroquinolones in the context of preventing and eradicating early lung infection and in managing chronic lung infection and pulmonary exacerbations. The safety of fluoroquinolones and the use of newer agents in the class are also discussed.

  3. Fluoroquinolones in the treatment of bronchopulmonary disease in cystic fibrosis

    PubMed Central

    2012-01-01

    Fluoroquinolones are commonly used to treat lung infections in those with cystic fibrosis. Patients with cystic fibrosis are susceptible to lung infection with common bacteria such as Staphylococcus aureus and Haemophilus influenzae, but also are prone to infection by opportunistic bacteria, including Pseudomonas aeruginosa. The good oral bioavailability and broad antimicrobial spectrum of activity, including anti-pseudomonal properties make this class of antimicrobial attractive. We review the evidence assessing the use of fluoroquinolones in the context of preventing and eradicating early lung infection and in managing chronic lung infection and pulmonary exacerbations. The safety of fluoroquinolones and the use of newer agents in the class is also discussed. PMID:22968160

  4. Quantitative Contributions of Target Alteration and Decreased Drug Accumulation to Pseudomonas aeruginosa Fluoroquinolone Resistance

    PubMed Central

    Bruchmann, Sebastian; Dötsch, Andreas; Nouri, Bianka; Chaberny, Iris F.

    2013-01-01

    Quinolone antibiotics constitute a clinically successful and widely used class of broad-spectrum antibiotics; however, the emergence and spread of resistance increasingly limits the use of fluoroquinolones in the treatment and management of microbial disease. In this study, we evaluated the quantitative contributions of quinolone target alteration and efflux pump expression to fluoroquinolone resistance in Pseudomonas aeruginosa. We generated isogenic mutations in hot spots of the quinolone resistance-determining regions (QRDRs) of gyrA, gyrB, and parC and inactivated the efflux regulator genes so as to overexpress the corresponding multidrug resistance (MDR) efflux pumps. We then introduced the respective mutations into the reference strain PA14 singly and in various combinations. Whereas the combined inactivation of two efflux regulator-encoding genes did not lead to resistance levels higher than those obtained by inactivation of only one efflux regulator-encoding gene, the combination of mutations leading to increased efflux and target alteration clearly exhibited an additive effect. This combination of target alteration and overexpression of efflux pumps was commonly observed in clinical P. aeruginosa isolates; however, these two mechanisms were frequently found not to be sufficient to explain the level of fluoroquinolone resistance. Our results suggest that there are additional mechanisms, independent of the expression of the MexAB-OprM, MexCD-OprJ, MexEF-OprN, and/or MexXY-OprM efflux pump, that increase ciprofloxacin resistance in isolates with mutations in the QRDRs. PMID:23274661

  5. Fluoroquinolone resistance of Escherichia coli and Salmonella from healthy livestock and poultry in the EU.

    PubMed

    de Jong, A; Stephan, B; Silley, P

    2012-02-01

    The potential for transmission of antibiotic-resistant enteric zoonotic bacteria from animals to humans has been a public health concern for several decades. Bacteria carrying antibiotic resistance genes found in the intestinal tract of food animals can contaminate carcasses and may lead to food-borne disease in humans that may not respond to antibiotic treatment. It is consequently important to monitor changes in antimicrobial susceptibility of zoonotic and commensal organism; in this context, there are a number of veterinary monitoring programmes that collect bacteria in food-producing animals at slaughter and determine their susceptibility against antibiotics relevant for human medicine. The data generated are part of the risk analysis for potential food-borne transmission of resistance. There has been much debate about the use of fluoroquinolones in veterinary medicine, and so, this review will consider the fluoroquinolone data from two surveys and compare them to national surveillance programmes. At the outset, it must be pointed out that there is, however, a lack of agreement between several programmes on what is meant by the term 'fluoroquinolone resistance' through use of different definitions of resistance and different resistance breakpoints. An additional aim of this paper is to clarify some of those definitions. Despite the debate about the contribution of antibiotic use in veterinary medicine to the overall resistance development in human pathogens, the data suggest that clinical resistance to fluoroquinolones in Escherichia coli and nontyphoidal Salmonella is generally uncommon, except for a few countries. Ongoing surveillance will continue to monitor the situation and identify whether this situation changes within the respective animal populations. For the benefit of both the epidemiologist and the clinician, it would be strongly advantageous that national monitoring surveys report both percentages of clinical resistance and decreased susceptibility

  6. High fluoroquinolone MIC is associated with fluoroquinolone treatment failure in urinary tract infections caused by fluoroquinolone susceptible Escherichia coli.

    PubMed

    Rattanaumpawan, Pinyo; Nachamkin, Irving; Bilker, Warren B; Roy, Jason A; Metlay, Joshua P; Zaoutis, Theoklis E; Lautenbach, Ebbing

    2017-04-08

    Suboptimal clinical response to fluoroquinolone (FQ) therapy has been clearly documented in patients with Salmonella typhi infection with reduced FQ susceptibility. However, the clinical impact of reduced FQ susceptibility on other infections including E. coli urinary tract infections (UTIs) has never been evaluated. We conducted a retrospective cohort study of female patients with fluoroquinolone susceptible E. coli (FQSEC) UTIs who received FQ therapy at outpatient services within University of Pennsylvania Health System, Philadelphia. Exposed patients were those with high MIC-FQSEC UTIs (the levofloxacin MIC > 0.12 but ≤ 2 mg/L) while unexposed patients were those with low MIC-FQSEC UTIs (the levofloxacin MIC ≤ 0.12 mg/L). The primary treatment outcome was treatment failure within 10 weeks after initiation of FQ therapy. From May 2008 to April 2011, we enrolled 29 exposed patients and 246 unexposed patients. Two patients in each group experienced treatment failure; exposed vs. unexposed (6.9 vs. 0.8%; p = 0.06). Risk difference and risk ratio (RR) for treatment failure were 0.06 [95% CI -0.03-0.15; exact-p = 0.06] and 8.48 [95% CI 1.24-57.97; exact-p = 0.06], respectively. After adjusting for underlying cerebrovascular disease, the RR was 7.12 (95% CI 1.20-42.10; MH-p = 0.04). Our study demonstrated the negative impact of reduced FQ susceptibility on the treatment response to FQ therapy in FQSEC UTIs. This negative impact may be more intensified in other serious infections. Future studies in other clinical situations should be conducted to fill the gap of knowledge.

  7. 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

  8. EDITORIAL: Special issue containing papers presented at the 4th IAEA Technical Meeting on the Theory of Plasma Instabilities Special issue containing papers presented at the 4th IAEA Technical Meeting on the Theory of Plasma Instabilities

    NASA Astrophysics Data System (ADS)

    Itoh, K.; Wilson, H. R.

    2010-05-01

    The 4th IAEA technical meeting (TM) on the Theory of Plasma Instabilities was held in Kyoto, May 18th--20th 2009, following the first (Seeon), second (Trieste) and third (York) meetings in this series. This IAEA-TM was motivated by the recent advances in theoretical methodology, the rapid progress in observations of laboratory and astrophysical plasmas and the evolution of fusion research as we approach the ITER era. The international advisory committee (IAC) and local organizing committee (LOC), the members of which are listed below, collaborated to define the scope and the content of the scientific programme. Young scientists were actively encouraged to participate in this TM to help stimulate their future research careers and raise their international profiles. Through these young scientists, the IAEA-TM planned to identify the future directions of research. About 90 researchers, from 13 countries and the IAEA, participated in this IAEA-TM, with 72 scientific presentations. The talks and posters generated enthusiastic discussions, contributing to the vibrancy of the meeting. This special issue of Nuclear Fusion consists of a cluster of papers, reporting some of the main contributions to the IAEA-TM. The articles in this cluster are representative of the scientific width of presentations at the meeting, spanning topics from micro-turbulence to large-scale MHD dynamics and from transport to detailed analysis of diagnostics. They demonstrate the quality and depth of the research presented at the conference. List of IAC (alphabetical order): B. Breizman (USA), S. Guenter (Germany), T. S. Hahm (USA), K. Itoh (Japan, Chair of 2009), Ya. I. Kolesnichenko (Ukraine), A. G. Peeters (UK), H. Wilson (UK) List of LOC (alphabetical order): A. Fukuyama, R. Horiuchi, S.-I. Itoh, N. Kasuya, Y. Kishimoto (co-chair), K. Kusano, J. Li, K. Mima, S. Murakami, H. Naitou, N. Nakajima, Y. Nakamura, H. Ohtani, S. Okamura, T. Ozeki, S. Sudo (co-chair), H. Sugama, Y. Todo, S. Tokuda, S

  9. Insight into Prodrugs of Quinolones and Fluoroquinolones.

    PubMed

    Sharma, Prabodh Chander; Piplani, Mona; Mittal, Monika; Pahwa, Rakesh

    2016-01-01

    Quinolones and fluoroquinolones are principal weapons against variety of bacterial infections and exert their antibacterial potential by interfering the activities of bacterial enzymes. As these agents are associated with some limitations, an important approach to overcome these major constraints is to prepare covalent derivatives, i.e. prodrugs. Prodrug design has been employed to improve the limitations of these drugs such as less aqueous solubility, poor absorption and distribution, toxicity, disagreeable taste, poor lipophilicity etc and for improving their pharmacological profile. This paper highlights the utility of various prodrug strategies in optimizing the therapeutic index of these antibacterial agents and their recent patents. Some of their prodrugs being utilized at preclinical and clinical levels have also been discussed. Hence, this paper has been prepared to present the significant findings of various research papers that would be helpful in motivating scientific researchers to forward the research in direction of utilization of prodrugs in clinical therapy.

  10. Torsades de pointes associated with fluoroquinolones.

    PubMed

    Owens, Robert C; Ambrose, Paul G

    2002-05-01

    Recent attention has been called to the interpretation of studies of antiinfective agents demonstrating effects on the QTc interval. It seems that the effects of many of these agents on the QTc interval are small, but in some patient populations, these drugs may cause morbidity and mortality related to TdP. It would be beneficial to researchers and clinicians alike for the FDA to standardize the types of studies designed to assess the QTc interval prolongation potential of a drug, methodologies, and interpretation criteria. To this end, it would increase the efficiency of the drug-approval process, give regulatory agencies and clinicians guidance, and increase patient safety. In summary we congratulate Dr. Frothingham for attempting to address the challenging issue of postmarketing safety surveillance. A critical review of his analysis of fluoroquinolone-associated TdP as well as other data on this potentially life-threatening adverse event support the following conclusions: Information from spontaneous reports is generally useful as an early warning system for excess adverse events, but reporting rates are not synonymous with incidence rates. The deficiencies of Dr. Frothingham's analysis lead to serious questions regarding the validity of both the numerators and denominators used in the incidence calculations (e.g., exclusion of European results, use ot extrapolated outpatient prescriptions, failure to account for inpatient versus outpatient utilization, failure to apply the appropriate statistical test to a rarely occurring, adverse event) and call into question conclusions about the relative risk of TdP with different fluoroquinolones. The association between which of the fluoroquinolones was administered to high-risk patients, which is important in the multiple-hit hypothesis, remains nebulous (e.g., failure to separate cases by route of drug administration and failure to identify which fluoroquinolones were given to patients with electrolyte abnormalities

  11. The first steps towards fluoroquinolone resistance in Hungarian pneumococci.

    PubMed

    Dobay, O; Rozgonyi, F; Ghidán, A; Matuz, M; Nagy, K; Amyes, S G B

    2006-12-01

    The incidence of fluoroquinolone resistance among Hungarian routine laboratory Streptococcus pneumoniae isolates, collected in 2000-2002, in common with other European countries, was very low; only 5/304 strains (1.64%) were resistant to ciprofloxacin (MIC = 4 microg/ml), and the other fluoroquinolones showed full efficacy. However, we could identify the Lys-137-Asp amino acid change, caused by a point mutation in the QRDR of the parC gene, in five strains. Additionally, we observed a definite shift in the minimum inhibitory concentrations (MICs) of all fluoroquinolones towards higher values throughout the study period. These two findings, coupled with the increasing consumption figures of fluoroquinolones, suggest that pneumococcal resistance looks poised to develop in Hungary.

  12. 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.

  13. 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.

  14. The relationship between snack intake and its availability of 4th-6th graders in Taiwan.

    PubMed

    Hang, Chi-Ming; Lin, Wei; Yang, Hsiao-Chi; Pan, Wen-Harn

    2007-01-01

    The purpose of this study was to examine the relationship between the snack intake and snack availability of elementary school children. Data analyzed were from 722 4th to 6th graders' food availability and food intake questionnaires collected in the Nutrition and Health Survey in Taiwan Elementary School Children 2001-2002. The snacks commonly eaten were divided into two groups. Healthy snacks included dairy products, 100% fruit juice and fresh fruits. Unhealthy snacks included high fat/sugar snacks, cookies, candy, carbonated/sugared beverages and fast food. Structural equating modeling was used to test the models that describe the availability and intake of two snack groups. Results indicated that parents' intake and children's preference were major predictors of children intake of both healthy and unhealthy snacks. Other than that, the intake of unhealthy snacks was positively associated with "purchase by children themselves" but not the intake of healthy snacks, which was influenced predominantly by "present in home". The results support the perception that a positive family food environment is important for improving children's diet quality. To build a healthy family food environment, parents have to not only provide healthy snacks but also limit the unhealthy snacks in home. In addition to that, the role modeling of parents as eating healthy snacks instead of unhealthy snacks themselves may help children to develop similar behaviors.

  15. Cutting orientations for non-complex parts in 4th axis machining

    NASA Astrophysics Data System (ADS)

    Osman Zahid, M. N.; Case, K.; Watts, D. M.

    2016-02-01

    The application of Computer Numerically Controlled (CNC) machining for Rapid Manufacturing processes (CNC-RM) exploits the innate potential of 4th axis machining. The use of an indexer allows the workpiece to be rotated to various orientations which directly increased the region accessible to the cutting tool. However, in order to avoid thin webs and preserve tool life, cutting must be executed with a minimum of three orientations even for geometrically simple parts. Recent findings have suggested the separation of cutting orientations into roughing and finishing operations. Thus, the selection of orientations in finishing processes becomes more flexible and independent. This study was conducted to identify the effects of using a minimum of two cutting orientations in finishing operations for CNC-RM applications. This method is only applicable for non-complex parts where all the features can be machined from two directions. The results of the study illustrate the positive effects of minimizing the number of orientations. Despite improvement in machining operations, the complexity in defining the cutting orientations was also reduced.

  16. Teaching systems thinking to 4th and 5th graders using Environmental Dashboard display technology

    PubMed Central

    Clark, Shane; Frantz, Cindy M.; Roose, Deborah; Ginn, Joel; Rosenberg Daneri, Daniel

    2017-01-01

    Tackling complex environmental challenges requires the capacity to understand how relationships and interactions between parts result in dynamic behavior of whole systems. There has been convincing research that these “systems thinking” skills can be learned. However, there is little research on methods for teaching these skills to children or assessing their impact. The Environmental Dashboard is a technology that uses “sociotechnical” feedback–information feedback designed to affect thought and behavior. Environmental Dashboard (ED) combines real-time information on community resource use with images and words that reflect pro-environmental actions of community members. Prior research indicates that ED supports the development of systems thinking in adults. To assess its impact on children, the technology was installed in a primary school and children were passively exposed to ED displays. This resulted in no measurable impact on systems thinking skills. The next stage of this research examined the impact of actively integrating ED into lessons on electricity in 4th and 5th grade. This active integration enhanced both content-related systems thinking skills and content retention. PMID:28448586

  17. 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

  18. 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.

  19. 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.

  20. 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."

  1. Putting agent-based modeling to work: results of the 4th International Project Albert Workshop

    NASA Astrophysics Data System (ADS)

    Horne, Gary E.; Bjorkman, Eileen A.; Colton, Trevor

    2002-07-01

    Project Albert is an initiative of the US Marine Corps which uses a series of new models and tools, multidisciplinary teams, and the scientific method to explore questions of interest to military planners. Project Albert attempts to address key areas that traditional modeling and simulation techniques often do not capture satisfactorily and uses two data management concepts, data farming and data mining, to assist in identifying areas of interest. The current suite of models used by Project Albert includes four agent-based models that allow agents to interact with each other and produce emergent behaviors. The 4th International Project Albert Workshop was held 6-9 August 2001 in Australia. Workshop participants split into five groups, each of which attempted to apply various combinations of the Project Albert models to answer a series of questions in five areas: Control Operations; Reconnaissance, Surveillance, and Intelligence Force Mix; Precision Maneuver; Mission Area Analysis; and Peace Support Operations. This paper focuses on the methodology used during the workshop, the results of the workshop, and a summary of follow-on work since the workshop.

  2. A 4th-order reconfigurable analog baseband filter for software-defined radio applications

    NASA Astrophysics Data System (ADS)

    Weiwei, Wang; Xuegui, Chang; Xiao, Wang; Kefeng, Han; Xi, Tan; Na, Yan; Hao, Min

    2011-04-01

    This paper presents a 4th-order reconfigurable analog baseband filter for software-defined radios. The design exploits an active-RC low pass filter (LPF) structure with digital assistant, which is flexible for tunability of filter characteristics, such as cut-off frequency, selectivity, type, noise, gain and power. A novel reconfigurable operational amplifier is proposed to realize the optimization of noise and scalability of power dissipation. The chip was fabricated in an SMIC 0.13 μm CMOS process. The main filter and frequency calibration circuit occupy 1.8 × 0.8 mm2 and 0.48 × 0.25 mm2 areas, respectively. The measurement results indicate that the filter provides Butterworth and Chebyshev responses with a wide frequency tuning range from 280 kHz to 15 MHz and a gain range from 0 to 18 dB. An IIP3 of 29 dBm is achieved under a 1.2 V power supply. The input inferred noise density varies from 41 to 133 according to a given standard, and the power consumptions are 5.46 mW for low band (from 280 kHz to 3 MHz) and 8.74 mW for high band (from 3 to 15 MHz) mode.

  3. 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

  4. Teaching systems thinking to 4th and 5th graders using Environmental Dashboard display technology.

    PubMed

    Clark, Shane; Petersen, John E; Frantz, Cindy M; Roose, Deborah; Ginn, Joel; Rosenberg Daneri, Daniel

    2017-01-01

    Tackling complex environmental challenges requires the capacity to understand how relationships and interactions between parts result in dynamic behavior of whole systems. There has been convincing research that these "systems thinking" skills can be learned. However, there is little research on methods for teaching these skills to children or assessing their impact. The Environmental Dashboard is a technology that uses "sociotechnical" feedback-information feedback designed to affect thought and behavior. Environmental Dashboard (ED) combines real-time information on community resource use with images and words that reflect pro-environmental actions of community members. Prior research indicates that ED supports the development of systems thinking in adults. To assess its impact on children, the technology was installed in a primary school and children were passively exposed to ED displays. This resulted in no measurable impact on systems thinking skills. The next stage of this research examined the impact of actively integrating ED into lessons on electricity in 4th and 5th grade. This active integration enhanced both content-related systems thinking skills and content retention.

  5. 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!

  6. Water quality and occurrence of water-borne diseases in the Douala 4th District, Cameroon.

    PubMed

    Ako, Andrew Ako; Nkeng, George Elambo; Takem, Gloria Eyong Eneke

    2009-01-01

    The monthly occurrence and mean age distribution of water-borne diseases in the Douala 4th District, Cameroon (1995-2006) were studied and probable causes of diseases spread were established. Diseases of interest included gastroenteritis, amoebic dysentery, typhoid fever and cholera. Water-borne disease occurrence was observed to follow a seasonal pattern with peaks occurring between the months of January and May followed by drops between June and October and rose again from November. Children below 5 years were found to be more vulnerable to diarrhoea, gastroenteritis, amoebic dysentery while persons between 15-44 years were more vulnerable to typhoid and cholera. Physico-chemically, water samples had turbidities varying between 5.5-86 NTU, pH values between 4.2 and 7.1 and zero residual chlorine. Bacteriological analysis showed that the total coliform count was averagely 74/100 ml, the faecal colform count was 43/100 ml and the faecal streptococci count was 27/100 ml. Lack of access to potable water, absence of sanitation facilities and environmental factors could be advanced as the probable causes of water-borne disease spread.

  7. 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).

  8. In vitro-selected resistance to fluoroquinolones in two Brucella strains associated with mutational changes in gyrA.

    PubMed

    Turkmani, Aun; Psaroulaki, Anna; Christidou, Athanasia; Chochlakis, Dimosthenis; Tabaa, Darem; Tselentis, Yannis

    2008-09-01

    In the present study, Brucella melitensis biovar Abortus 2308 and Brucella abortus 3196 biotype 5 reference strains, which are susceptible to fluoroquinolones, became in vitro-resistant to fluoroquinolones by culture in trypticase soy agar. The quinolone resistance-determining regions (QRDRs) of the gyrA and parC genes of the two reference strains were analysed by polymerase chain reaction sequencing analysis to obtain the wild-type sequence. These sequences were then compared with the corresponding sequences of four in vitro-selected fluoroquinolone-resistant mutants to characterise mutations associated with resistance. Sequencing of the ofloxacin-selected resistant mutant 2308 revealed a transition of GAT to AAT (corresponding to position 87 of Escherichia coli gyrA), leading to substitution of Asp91-->Asn, whilst at the same position the ciprofloxacin-selected resistant mutant 2308 revealed a transition of GAT to TAT (corresponding to the same position of E. coli as above), leading to substitution of Asp91-->Tyr. The ofloxacin-selected resistant mutant 3196 had a transition of GCT to GTT, generating an amino acid change of Ala87-->Val. Amino acid changes were detected in the portion of the Brucella gyrA gene (Ala71 to Gln110) corresponding to the E. coli gyrA QRDR region (Ala67 to Gln110). Amino acid changes were also detected in Ser83, corresponding to the region where fluoroquinolone-associated amino acid changes are most commonly found in other bacterial species.

  9. Emergence and maintenance of resistance to fluoroquinolones and coumarins in Staphylococcus aureus: predictions from in vitro studies.

    PubMed

    Vickers, A A; O'Neill, A J; Chopra, I

    2007-08-01

    Fluoroquinolones and coumarins interfere with the activity of bacterial type II topoisomerase enzymes. We examined the development of resistance to these agents in Staphylococcus aureus and determined the effect of simultaneous topoisomerase IV and DNA gyrase mutations on the biological fitness of the organism. This work aimed to gain insight into how such mutants might arise and survive in the clinical environment. Spontaneous mutants resistant to fluoroquinolones and coumarins were selected in S. aureus. Resistance mutations were identified by DNA sequencing of PCR amplicons corresponding to the genes encoding topoisomerase IV and DNA gyrase. In vitro fitness of resistant mutants was compared with the antibiotic-susceptible progenitor strain using pair-wise competition assays. Mutants simultaneously resistant to both a fluoroquinolone and either of the coumarins, novobiocin or coumermycin A1, could not be recovered following a single-step selection. However, mutants concurrently resistant to both classes of antimicrobial could be generated by step-wise selections. These mutants demonstrated reductions in competitive fitness of up to 36%. Dual-targeting of topoisomerase IV and DNA gyrase enzymes, for example with the combination of a fluoroquinolone and a coumarin agent, could minimize the emergence of resistance to these drugs in S. aureus. However, resistance-associated fitness costs may not be sufficient to limit the survival of mutants with dual resistance, if they arose in the clinical setting.

  10. Lomefloxacin and temafloxacin: two new fluoroquinolone antimicrobials.

    PubMed

    Symonds, W T; Nix, D E

    1992-09-01

    The chemistry, mechanism of action, antimicrobial spectrum, pharmacokinetics, clinical efficacy, safety, drug interactions, and dosage and administration of lomefloxacin and temafloxacin, two new antimicrobials, are presented. Lomefloxacin and temafloxacin exhibit activity comparable to that of ciprofloxacin against the Enterobacteriaceae. Lomefloxacin has only modest activity against common gram-positive organisms. Temafloxacin exhibits increased activity against the streptococci and moderate activity against many anaerobes, as compared with ciprofloxacin. Lomefloxacin and temafloxacin have only moderate antipseudomonal activity. Their elimination half-lives are 6-10 hours and they have good oral absorption, excellent penetration into many tissues and fluids, and a better drug-interaction profile than other similar agents. Lomefloxacin has demonstrated comparable efficacy to other therapies in the treatment of lower respiratory-tract infections and urinary-tract infections (UTIs) and for prophylaxis before surgical procedures in the urinary tract. Temafloxacin has been shown to be effective in the treatment of lower respiratory-tract infections, infections of the skin and associated structures, uncomplicated and complicated UTIs, bacterial prostatitis, and gonococcal and non-gonococcal urethritis and cervicitis. The most frequent adverse effects with lomefloxacin are gastrointestinal upset and headache; with temafloxacin, gastrointestinal complaints. Lomefloxacin's dosage is 400 mg p.o. daily for 10 days for treatment of acute bacterial exacerbations in chronic bronchitis or simple cystitis and for 14 days for treatment of complicated UTIs. Lomefloxacin is a new oral fluoroquinolone that is indicated for the treatment of various bacterial infections. Temafloxacin, another new fluoroquinolone, appeared to have some favourable characteristics but was withdrawn from the market.

  11. Proposal to sup[port the 4th international conference on nitrification and related processes (ICoN4)

    SciTech Connect

    Klotz, Martin Gunter

    2016-11-04

    The 4th International Conference on Nitrification and Related Processes (ICoN4) commencing between June 27 and July 1, 2015, at the University of Alberta in Edmonton, Alberta, Canada brings together an international collection of academic, government, and private sector researchers of the global biogeochemical nitrogen cycle to share their scientific discoveries, innovations and pertinent societal impacts. The classical understanding of “nitrification” describes the two-step transformation of ammonium to nitrite and nitrite to nitrate; however, we now know from the analysis genome sequences, the application of ‘omics technologies, microbial ecology, biogeochemistry, and microbial physiology that the transformation of ammonium is not performed by a few particular groups of microorganisms nor is it confined to oxic environments. Past ICoN meetings have explored the interconnections between ammonium- and nitrite-consuming processes in all ecosystems, the emission of greenhouse gases by these processes and their control, and the intersection between intermediates of the nitrification process and other elemental cycles; this has generated tremendous progress in our understanding of the global nitrogen cycle and it has generated excitement in the next generation of N cycle researchers. Nitrification research has a long-standing connection to the Community Science Program of the DOE. Between 1999 and 2001, the JGI generated the first genome sequence of an ammonia-oxidizing bacterium, Nitrosomonas europaea ATCC 19718, and it has subsequently sequenced, or is in the process of sequencing over 50 additional genomes from ammonia-oxidizing bacteria, nitrite-oxidizing bacteria, and ammonia-oxidizing archaea. Autotrophic ammonia- and nitrite-transforming microorganisms play also a critical role in carbon cycling and sequestration in nearly all ecosystems. Not only do they control the concentration and speciation of biologically available N to plants and other

  12. Resistance surveillance studies: a multifaceted problem--the fluoroquinolone example.

    PubMed

    Dalhoff, A

    2012-06-01

    This review summarizes data on the fluoroquinolone resistance epidemiology published in the previous 5 years. The data reviewed are stratified according to the different prescription patterns by either primary- or tertiary-care givers and by indication. Global surveillance studies demonstrate that fluoroquinolone- resistance rates increased in the past several years in almost all bacterial species except Staphylococcus pneumoniae and Haemophilus influenzae causing community-acquired respiratory tract infections (CARTIs), as well as Enterobacteriaceae causing community-acquired urinary tract infections. Geographically and quantitatively varying fluoroquinolone resistance rates were recorded among Gram-positive and Gram-negative pathogens causing healthcare-associated respiratory tract infections. One- to two-thirds of Enterobacteriaceae producing extended-spectrum β-lactamases (ESBLs) were fluoroquinolone resistant too, thus, limiting the fluoroquinolone use in the treatment of community- as well as healthcare-acquired urinary tract and intra-abdominal infections. The remaining ESBL-producing or plasmid-mediated quinolone resistance mechanisms harboring Enterobacteriaceae were low-level quinolone resistant. Furthermore, 10-30 % of H. influenzae and S. pneumoniae causing CARTIs harbored first-step quinolone resistance determining region (QRDR) mutations. These mutants pass susceptibility testing unnoticed and are primed to acquire high-level fluoroquinolone resistance rapidly, thus, putting the patient at risk. The continued increase in fluoroquinolone resistance affects patient management and necessitates changes in some current guidelines for the treatment of intra-abdominal infections or even precludes the use of fluoroquinolones in certain indications like gonorrhea and pelvic inflammatory diseases in those geographic areas in which fluoroquinolone resistance rates and/or ESBL production is high. Fluoroquinolone resistance has been selected among the commensal

  13. Humoral immunity and CD4+ Th1 cells are both necessary for a fully protective immune response upon secondary infection with Brucella melitensis.

    PubMed

    Vitry, Marie-Alice; Hanot Mambres, Delphine; De Trez, Carl; Akira, Shizuo; Ryffel, Bernhard; Letesson, Jean-Jacques; Muraille, Eric

    2014-04-15

    Brucella spp are intracellular bacteria that cause brucellosis, one of the most common zoonoses in the world. Given the serious medical consequences of this disease, a safe and effective human vaccine is urgently needed. Efforts to develop this vaccine have been hampered by our lack of understanding of what constitutes a protective memory response against Brucella. In this study, we characterize the cells and signaling pathways implicated in the generation of a protective immune memory response following priming by the injection of heat-killed or live Brucella melitensis 16M. Using a panel of gene-deficient mice, we demonstrated that during a secondary recall response, both the Brucella-specific humoral response and CD4+ Th1 cells must act together to confer protective immunity in the spleen to B. melitensis infection. Humoral protective immunity is induced by the inoculation of both heat-killed and live bacteria, and its development does not require T cells, MyD88/IL-12p35 signaling pathways, or an activation-induced deaminase-mediated isotype switch. In striking contrast, the presence of memory IFN-γ-producing CD4+ Th1 cells requires the administration of live bacteria and functional MyD88/IL-12p35 pathways. In summary, our work identifies several immune markers closely associated with protective immune memory and could help to define a rational strategy to obtain an effective human vaccine against brucellosis.

  14. 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.

  15. 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. Copyright © 2015 International Agency for Research on Cancer. Published by Elsevier Ltd. All rights reserved.

  16. 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

  17. 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."

  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. 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

  20. 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.

  1. Late-breaking news from the "4th International Meeting on Inflammatory Bowel Diseases" Capri, 2006.

    PubMed

    Latella, Giovanni; Fiocchi, Claudio; Caprilli, Renzo

    2007-08-01

    At the "4th International Meeting on Inflammatory Bowel Diseases: on the Way to New Therapies," Capri, 2006, genetics, bacteria-host interactions, immunomodulation, and tissue response were discussed deeply in order to understand, rationalize, and develop novel therapies. About genetics, the importance of a better understanding of the nature of known loci and of the putative associations was stressed. It was confirmed that genotype-phenotype associations in inflammatory bowel disease (IBD) have important clinical and therapeutic implications. The importance of the search for dominant bacterial antigens in chronic immune-mediated intestinal inflammation emerged, as well as knowledge of cellular and molecular mechanisms of bacterial-host interactions. It was discussed how innate and adaptive immunity signaling events can perpetuate chronic inflammation. Signal transduction pathways provide an intracellular mechanism by which cells respond and adapt to environmental stress. The identification of these signals have led to a greater understanding of the pathogenesis of IBD and pointed to potential therapeutic targets. It was shown that immune homeostasis is lost in IBD, resulting in a complex tissue response involving the action of immune and nonimmune cells. The nonimmune tissue response in IBD could be regarded as a new target for control of chronic intestinal inflammation. The changing role of biotherapy in IBD was widely discussed and in particular the anti-TNF-alpha monoclonal antibodies. Granulocyte-colony stimulating factor (GM-CSF) and stem cells therapies were also discussed. The risk-to-benefit ratio of the novel therapies was analyzed in detail. Finally, future directions for basic science and the unmet needs for clinical practice were presented.

  2. 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.

  3. Direct Photolysis of Fluoroquinolone Antibiotics at 253.7 nm: Specific Reaction Kinetics and Formation of Equally Potent Fluoroquinolone Antibiotics.

    PubMed

    Snowberger, Sebastian; Adejumo, Hollie; He, Ke; Mangalgiri, Kiranmayi P; Hopanna, Mamatha; Soares, Ana Dulce; Blaney, Lee

    2016-09-06

    Three fluoroquinolone-to-fluoroquinolone antibiotic transformations were monitored during UV-C irradiation processes. In particular, the following reactions were observed: enrofloxacin-to-ciprofloxacin, difloxacin-to-sarafloxacin, and pefloxacin-to-norfloxacin. The apparent molar absorptivity and fluence-based pseudo-first-order rate constants for transformation of the six fluoroquinolones by direct photolysis at 253.7 nm were determined for the pH 2-12 range. These parameters were deconvoluted to calculate specific molar absorptivity and fluence-based rate constants for cationic, zwitterionic, and anionic fluoroquinolone species. For a typical disinfection fluence of 40 mJ/cm(2), the apparent transformation efficiencies were inflated by 2-8% when fluoroquinolone products were not considered; moreover, the overall transformation efficiencies at 400 mJ/cm(2) varied by up to 40% depending on pH. The three product antibiotics, namely ciprofloxacin, sarafloxacin, and norfloxacin, were found to be equally or more potent than the parent fluoroquinolones using an Escherichia coli-based assay. UV treatment of a solution containing difloxacin was found to increase antimicrobial activity due to formation of sarafloxacin. These results highlight the importance of considering antibiotic-to-antibiotic transformations in UV-based processes.

  4. Tendon Injury and Fluoroquinolone Use: A Systematic Review.

    PubMed

    Stephenson, Anne L; Wu, Wei; Cortes, Daniel; Rochon, Paula A

    2013-09-01

    Fluoroquinolone antibiotics are commonly used to treat infections and are prescribed by general practitioners, medical specialists and surgeons. Tendon injury has been associated with the use of these medications but the risk associated with newer fluoroquinolones has not been established. The aim of this systematic review was to evaluate the evidence from observational studies to determine the strength of the association between fluoroquinolone use and tendinopathy, and to identify risk factors for this complication. We searched MEDLINE, EMBASE and the Cochrane Collaboration from inception through May 2013 to identify observational studies focused on tendon injury and fluoroquinolones. Studies with original data were selected for inclusion following the PRISMA guidelines. Of the 560 abstracts screened, 16 relevant studies were independently rated by three authors (WW, AS, DC) using the Newcastle-Ottawa Quality Assessment Scale, and assigned a quality score out of 9. High-quality studies (i.e. scored 4.5 or higher) are summarized in detail in this article. Data were independently extracted by two authors (WW, AS). Overall, 16 studies were included in our study. Eight were deemed to be of high quality and five specifically evaluated Achilles tendon rupture. In addition, three studies examined Achilles tendinitis, and three included tendon disorders (including any tendon rupture) as an outcome. Results from these studies suggest that individuals exposed to fluoroquinolones are at increased risk for Achilles tendon rupture, particularly within the first month following exposure to the drug (odds ratios ranged from 1.1 to 7.1). One study showed an increased risk of tendon rupture in those over 60 years of age. Five studies stated that individuals taking fluoroquinolones and oral corticosteroids are at increased risk for tendon injury compared with those taking fluoroquinolones alone. Four studies examined the differential effect of a limited number of fluoroquinolones

  5. A nosocomial outbreak of fluoroquinolone-resistant salmonella infection.

    PubMed

    Olsen, S J; DeBess, E E; McGivern, T E; Marano, N; Eby, T; Mauvais, S; Balan, V K; Zirnstein, G; Cieslak, P R; Angulo, F J

    2001-05-24

    Infection with fluoroquinolone-resistant strains of salmonella is rare, as is nosocomial salmonella infection. We describe the first recognized outbreak of fluoroquinolone-resistant salmonella infections in the United States, which occurred in two nursing homes and one hospital in Oregon. We interviewed medical staff and reviewed patients' charts and death certificates. In Nursing Home A we conducted a case-control study. Patients were defined as residents of the nursing home from whom fluoroquinolone-resistant Salmonella enterica serotype Schwarzengrund was isolated between February 1996 and December 1998. Controls were residents with similar medical conditions whose cultures did not yield salmonella. We compared isolates using pulsed-field gel electrophoresis and sequence analysis. We reviewed pharmacy records to compare the use of fluoroquinolone among several nursing homes. Eleven patients with fluoroquinolone-resistant salmonellosis were identified at two nursing homes. The index patient had been hospitalized in the Philippines and had probably acquired the infection there. Transmission was probably direct (from patient to patient) or through contact with contaminated surfaces. Treatment with fluoroquinolones during the six months before a culture was obtained was associated with a significant risk of salmonella infection (4 of 5 patients had taken fluoroquinolones, as compared with 2 of 13 controls; odds ratio, 22.0; 95 percent confidence interval, 1.06 to 1177). The patients were not significantly more likely than the controls to have taken other antibiotics. More fluoroquinolones were used at Nursing Home A than at similar nursing homes in Oregon. The isolates from the outbreak had similar patterns on pulsed-field gel electrophoresis and the same gyrA mutations. The isolates from the outbreak were also similar to the only previous isolate of fluoroquinolone-resistant salmonella in the United States, which came from a patient in New York who had been

  6. 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…

  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. 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…

  9. 76 FR 72957 - 4th Annual Trauma Spectrum Conference: Bridging the Gap Between Research and Clinical Practice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-28

    ... HUMAN SERVICES National Institutes of Health 4th Annual Trauma Spectrum Conference: Bridging the Gap Between Research and Clinical Practice of Psychological Health and Traumatic Brain Injury: Prevention... Psychological Health and Traumatic Brain Injury: Prevention, Diagnosis, Treatment and Recovery for the Iraq...

  10. Teacher Implementation of Reform-Based Mathematics and Implications for Algebra Readiness: A Qualitative Study of 4th Grade Classrooms

    ERIC Educational Resources Information Center

    Sher, Stephen Korb

    2011-01-01

    This study looked at 4th grade classrooms to see "how" teachers implement NCTM standards-based or reform-based mathematics instruction and then analyzed it for the capacity to improve students' "algebra readiness." The qualitative study was based on classroom observations, teacher and administrator interviews, and teacher surveys. The study took…

  11. 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

    ... rule. SUMMARY: The Coast Guard is establishing a temporary safety zone in the navigable waters of Weber... Stockton 4th of July Fireworks Display on July 4, 2010, on the navigable waters of Weber Point, off of... temporary safety zone is established for the waters of Weber Point off of Stockton, CA. The fireworks launch...

  12. Analysis of Lexical Quality and Its Relation to Writing Quality for 4th Grade, Primary School Students in Chile

    ERIC Educational Resources Information Center

    Gómez Vera, Gabriela; Sotomayor, Carmen; Bedwell, Percy; Domínguez, Ana María; Jéldrez, Elvira

    2016-01-01

    Few studies have addressed vocabulary quality in developing writing skill in Spanish. Even less addressed it within the Chilean educational system. The specific objective of this study was to characterize, using a comprehensive set of indicators, the quality of the vocabulary produced by Chilean 4th grade students. Based on a national writing…

  13. 76 FR 33157 - Safety Zones; July 4th Fireworks Displays Within the Captain of the Port Miami Zone, FL

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-08

    ... Coast Guard is establishing temporary safety zones during Fourth of July fireworks events on the... displays are planned for the Fourth of July celebration throughout the Captain of the Port Miami Zone. The... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zones; July 4th Fireworks Displays Within the...

  14. 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…

  15. Comparative analysis of 1st, 2nd, and 4th year MD students' attitudes toward Complementary Alternative Medicine (CAM)

    PubMed Central

    Riccard, Christopher P; Skelton, Michele

    2008-01-01

    Background To identify and report the attitudes and beliefs of 1st, 2nd, and 4th year medical students toward complementary alternative medicine (CAM). Methods The previously validated and reliability tested CHBQ was administered to medical students attending the University of South Florida School of Medicine. Results Significant changes were found between both 1st (46.0 ± 7.7) and 4th (37.8 ± 15.7) year students and 2nd (48.3 ± 7.8) and 4th (37.8 ± 15.7) year students. No significant difference was found between 1st (46.0 ± 7.7) and 2nd (48.3 ± 7.8) year students. When comparing scores based on gender, a significant difference was present between males (41.2 ± 12.2) and females (46.1 ± 11.0). Conclusion CHBQ scores were significantly more positive in both 1st and 2nd year medical students in comparison with 4th year student's scores. These findings suggest that as student exposure to allopathic techniques and procedures increases during the last year of medical school, their attitudes toward CAM decrease. Females were also significantly more likely to have stronger positive attitudes toward CAM than males, though both genders represented an overall positive attitude toward CAM. PMID:18799010

  16. 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

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zones; City of Chicago's July 4th Celebration Fireworks, Lake Michigan, Chicago, IL AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast Guard is establishing two temporary safety zones on Lake Michigan near Chicago, Illinois. These...

  17. 75 FR 22330 - Safety Zone; City of Chicago's July 4th Celebration Fireworks, Lake Michigan, Chicago, IL

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-28

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; City of Chicago's July 4th Celebration Fireworks, Lake Michigan, Chicago, IL AGENCY: Coast Guard, DHS. ACTION: Notice of proposed rulemaking. SUMMARY: The Coast Guard proposes to establish a safety zone on Lake Michigan near Chicago, Illinois. This...

  18. Effect of the SQ4R Technique on the Reading Comprehension of Elementary School 4th Grade Elementary School Students

    ERIC Educational Resources Information Center

    Basar, Murat; Gürbüz, Mehmet

    2017-01-01

    The aim of this study is to examine the effect of SQ4R (Survey, Question, Read, Reflect, Recite, Review) technique of the reading comprehension ability of elementary school 4th grade students. The sampling was constituted by 57 students from two different branches of the Ataturk Elementary School in the center of Usak region during the 2nd…

  19. 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 is...

  20. 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…

  1. 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…

  2. 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…

  3. 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…

  4. Detection of antibiotics in food: extraction of fluoroquinolones by DNA.

    PubMed

    Cao, Limin; Lin, Hong; Mirsky, Vladimir M

    2007-05-01

    The ability of DNA to extract fluoroquinolones from model solutions and real probes of food was demonstrated and investigated quantitatively. The interaction between fluoroquinolones and different types of DNA was studied by equilibrium dialysis. The first application of this direct approach allowed us to determine binding constants and binding stoichiometries in different conditions. The binding of enrofloxacin to heat-denatured DNA (d-DNA) from herring sperm is pH- and magnesium-dependent; the highest fraction of bound drugs was found at pH 7 and a magnesium concentration of 0.5-1 mM. Results for three types of DNA: d-DNA, double-stranded DNA and single-stranded DNA were compared. The unwound DNA showed almost doubled binding constants and stoichiometries, thus indicating preferable interaction of enrofloxacin with single-strand regions of DNA. The binding of other fluoroquinolones (lomefloxacin, ciprofloxacin, norfloxacin, danofloxacin and sarafloxacin) with d-DNA is very similar to that of enrofloxacin: the binding constants are in the range from 0.94x10(5) to 2.40x10(5) M-1, and the stoichiometries range from 4.1 to 6.9 fluoroquinolone molecules per 100 DNA bases. The binding properties were quantitatively the same for extraction of fluoroquinolones from model aqueous solutions and from liquid food (milk). The results indicate the efficiency of DNA for selective extraction of fluoroquinolones from real samples for further analysis. This selective binding also allows us to consider DNA as a natural receptor for development of analytical techniques for fluoroquinolones.

  5. Outcomes following surgical repair using layered closure of unrepaired 4th degree perineal tear in rural western Uganda.

    PubMed

    Goh, Judith T W; Tan, Stephanie B M; Natukunda, Harriet; Singasi, Isaac; Krause, Hannah G

    2016-11-01

    In many rural low-income countries, perineal tears at time of vaginal birth are not repaired at time of delivery. The aims of this study are to describe the surgical technique for management of the unrepaired 4th degree tear, performed without flaps, and short-term follow up on anal incontinence symptoms using a validated questionnaire. Women presenting to fistula camps in western Uganda with unrepaired 4th degree tears were interviewed using the Cleveland Clinic Continence Score. Interviews were undertaken pre-operatively, at 4-6 weeks post-operatively and 12 months following surgery. Repair of the 4th degree tear was performed in layers, with an overlapping anal sphincter repair and reconstruction of the perineal body, without flaps. All women were examined prior to discharge. 68 women completed pre-operative Cleveland Clinic Continence Scores. Prior to surgery, 59 % of women complained of daily incontinence to solid stools. Over 70 % of women complained of restriction to lifestyle due to the unrepaired 4th degree tear. About 50 % of the women are rejected by their husbands because of the condition. Only 1 woman had wound breakdown on Day 2. At 4 to 6 weeks follow-up, 61 women were contacted and all reported perfect continence. This study highlights the hidden problem of unrepaired 4th degree tears in rural areas of low-income countries where most deliveries are undertaken in the village without professional health care workers. These tears have significant impact on quality of life and anal incontinence. Short-term outcomes following surgical repair using a layered closure are promising.

  6. The Effect of Primer Application Modifications on the Bond Strength of 4th Generation Adhesive Bonding Agents

    DTIC Science & Technology

    2012-03-30

    The influence of deviations from the manufacturer’s instructions for the use of six adhesive systems on the bond strengths to enamel and dentin...application of two layers of the self- etching adhesive systems produced significant improvement in bond strength to enamel compared to the passive...2010) evaluated the relationship between the number of adhesive layers and internal adaptation on the microtensile bond strength to enamel and dentin

  7. Computational Fluid Dynamics (CFD) study of the 4th generation prototype of a continuous flow Ventricular Assist Device (VAD).

    PubMed

    Song, Xinwei; Wood, Houston G; Olsen, Don

    2004-04-01

    The continuous flow ventricular assist device (VAD) is a miniature centrifugal pump, fully suspended by magnetic bearings, which is being developed for implantation in humans. The CF4 model is the first actual prototype of the final design product. The overall performances of blood flow in CF4 have been simulated using computational fluid dynamics (CFD) software: CFX, which is commercially available from ANSYS Inc. The flow regions modeled in CF4 include the inlet elbow, the five-blade impeller, the clearance gap below the impeller, and the exit volute. According to different needs from patients, a wide range of flow rates and revolutions per minute (RPM) have been studied. The flow rate-pressure curves are given. The streamlines in the flow field are drawn to detect stagnation points and vortices that could lead to thrombosis. The stress is calculated in the fluid field to estimate potential hemolysis. The stress is elevated to the decreased size of the blood flow paths through the smaller pump, but is still within the safe range. The thermal study on the pump, the blood and the surrounding tissue shows the temperature rise due to magnetoelectric heat sources and thermal dissipation is insignificant. CFD simulation proved valuable to demonstrate and to improve the performance of fluid flow in the design of a small size pump.

  8. 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

  9. 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

  10. 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

  11. Nonantibiotic Effects of Fluoroquinolones in Mammalian Cells.

    PubMed

    Badal, Sujan; Her, Yeng F; Maher, L James

    2015-09-04

    Fluoroquinolones (FQ) are powerful broad-spectrum antibiotics whose side effects include renal damage and, strangely, tendinopathies. The pathological mechanisms underlying these toxicities are poorly understood. Here, we show that the FQ drugs norfloxacin, ciprofloxacin, and enrofloxacin are powerful iron chelators comparable with deferoxamine, a clinically useful iron-chelating agent. We show that iron chelation by FQ leads to epigenetic effects through inhibition of α-ketoglutarate-dependent dioxygenases that require iron as a co-factor. Three dioxygenases were examined in HEK293 cells treated with FQ. At sub-millimolar concentrations, these antibiotics inhibited jumonji domain histone demethylases, TET DNA demethylases, and collagen prolyl 4-hydroxylases, leading to accumulation of methylated histones and DNA and inhibition of proline hydroxylation in collagen, respectively. These effects may explain FQ-induced nephrotoxicity and tendinopathy. By the same reasoning, dioxygenase inhibition by FQ was predicted to stabilize transcription factor HIF-1α by inhibition of the oxygen-dependent hypoxia-inducible transcription factor prolyl hydroxylation. In dramatic contrast to this prediction, HIF-1α protein was eliminated by FQ treatment. We explored possible mechanisms for this unexpected effect and show that FQ inhibit HIF-1α mRNA translation. Thus, FQ antibiotics induce global epigenetic changes, inhibit collagen maturation, and block HIF-1α accumulation. We suggest that these mechanisms explain the classic renal toxicities and peculiar tendinopathies associated with FQ antibiotics. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Nonantibiotic Effects of Fluoroquinolones in Mammalian Cells*

    PubMed Central

    Badal, Sujan; Her, Yeng F.; Maher, L. James

    2015-01-01

    Fluoroquinolones (FQ) are powerful broad-spectrum antibiotics whose side effects include renal damage and, strangely, tendinopathies. The pathological mechanisms underlying these toxicities are poorly understood. Here, we show that the FQ drugs norfloxacin, ciprofloxacin, and enrofloxacin are powerful iron chelators comparable with deferoxamine, a clinically useful iron-chelating agent. We show that iron chelation by FQ leads to epigenetic effects through inhibition of α-ketoglutarate-dependent dioxygenases that require iron as a co-factor. Three dioxygenases were examined in HEK293 cells treated with FQ. At sub-millimolar concentrations, these antibiotics inhibited jumonji domain histone demethylases, TET DNA demethylases, and collagen prolyl 4-hydroxylases, leading to accumulation of methylated histones and DNA and inhibition of proline hydroxylation in collagen, respectively. These effects may explain FQ-induced nephrotoxicity and tendinopathy. By the same reasoning, dioxygenase inhibition by FQ was predicted to stabilize transcription factor HIF-1α by inhibition of the oxygen-dependent hypoxia-inducible transcription factor prolyl hydroxylation. In dramatic contrast to this prediction, HIF-1α protein was eliminated by FQ treatment. We explored possible mechanisms for this unexpected effect and show that FQ inhibit HIF-1α mRNA translation. Thus, FQ antibiotics induce global epigenetic changes, inhibit collagen maturation, and block HIF-1α accumulation. We suggest that these mechanisms explain the classic renal toxicities and peculiar tendinopathies associated with FQ antibiotics. PMID:26205818

  13. Fluoroquinolones in children: update of the literature.

    PubMed

    Bacci, Caterina; Galli, Luisa; de Martino, Maurizio; Chiappini, Elena

    2015-10-01

    The use of fluoroquinolones (FQ), antibiotics, which have excellent pharmacokinetic and pharmacodynamic characteristics and a broad spectrum of action, has increased dramatically in recent years, both in adults and children. Numerous safety and efficacy data are now available on FQ use in children, particularly regarding the treatment of complicated infections of the urinary tract, typhoid fever, pneumonia, acute external otitis, acute media otitis, meningoencephalitis, sepsis in neutropenic children and multidrug-resistant tuberculosis (MDR-TB), though sometimes studies have the limitations that they were conducted in selected populations, such as children with cystic fibrosis. Despite available safety data are encouraging, there is still an open debate on the toxicity of this class of antibiotics on weight-bearing joints in children. Not being able to exclude the possibility that, in rare cases, this event is likely to occur, their use in children should be limited to cases where the cost-benefit has been carefully examined, for example, in the case of sepsis or other severe infections from multi-resistant bacteria and not responsive to other classes of drugs. Furthermore, considering the increased use of FQ in children, it is possible that there is an increase in the incidence of infections from resistant germs (such as Escherichia coli, and pneumococci), as occurred in adults. In order to limit the diffusion of resistance, a judicious and appropriate use of this class of drugs is recommended.

  14. A critical review of the fluoroquinolones: focus on respiratory infections.

    PubMed

    Zhanel, George G; Ennis, Kelly; Vercaigne, Lavern; Walkty, Andrew; Gin, Alfred S; Embil, John; Smith, Heather; Hoban, Daryl J

    2002-01-01

    The new fluoroquinolones (clinafloxacin, gatifloxacin, gemifloxacin, grepafloxacin, levofloxacin, moxifloxacin, sitafloxacin, sparfloxacin and trovafloxacin) offer excellent activity against Gram-negative bacilli and improved Gram-positive activity (e.g. against Streptococcus pneumoniae and Staphylococcus aureus) over ciprofloxacin. Ciprofloxacin still maintains the best in vitro activity against Pseudomonas aeruginosa. Clinafloxacin, gatifloxacin, moxifloxacin, sitafloxacin, sparfloxacin and trovafloxacin display improved activity against anaerobes (e.g. Bacteroides fragilis) versus ciprofloxacin. All of the new fluoroquinolones display excellent bioavailability and have longer serum half-lives than ciprofloxacin allowing for once daily dose administration. Clinical trials comparing the new fluoroquinolones to each other or to standard therapy have demonstrated good efficacy in a variety of community-acquired respiratory infections (e.g. pneumonia, acute exacerbations of chronic bronchitis and acute sinusitis). Limited data suggest that the new fluoroquinolones as a class may lead to better outcomes in community-acquired pneumonia and acute exacerbations of chronic bronchitis versus comparators. Several of these agents have either been withdrawn from the market, had their use severely restricted because of adverse effects (clinafloxacin because of phototoxicity and hypoglycaemia; grepafloxacin because of prolongation of the QTc and resultant torsades de pointes; sparfloxacin because of phototoxicity; and trovafloxacin because of hepatotoxicity), or were discontinued during developmental phases. The remaining fluoroquinolones such as gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin have adverse effect profiles similar to ciprofloxacin. Extensive post-marketing safety surveillance data (as are available with ciprofloxacin and levofloxacin) are required for all new fluoroquinolones before safety can be definitively established. Drug interactions are limited

  15. Mechanisms of resistance to fluoroquinolones and carbapenems in Pseudomonas putida.

    PubMed

    Horii, Toshinobu; Muramatsu, Hideaki; Iinuma, Yoshitsugu

    2005-10-01

    Pseudomonas putida is an uncommon opportunistic pathogen, usually susceptible to antimicrobial agents. Data concerning resistance to antimicrobial agents in clinical P. putida isolates are limited. Susceptibilities to fluoroquinolones, carbapenems and other antibiotics were characterized in five clinical isolates of P. putida recovered from different patients with urinary tract infections as causative pathogens. Fluoroquinolone and carbapenem resistance were characterized genetically by the methods of PCR and DNA sequencing. Outer membrane protein (OMP) profiles were characterized by SDS-PAGE. Four of five isolates were resistant or intermediate to both fluoroquinolones and carbapenems. Nucleotide sequences in the quinolone resistance-determining regions suggested that amino acid mutations such as Thr-83-->Ile in GyrA and Glu-469-->Asp in GyrB may contribute to high resistance to fluoroquinolones. Four metallo-beta-lactamase-producing isolates that showed resistance to carbapenems carried the IMP-type metallo-beta-lactamase genes. A combined effect of reduced production of 46 kDa OMP and metallo-beta-lactamase production was shown by a P. putida isolate exhibiting the highest MICs of carbapenems. This study identified mechanisms of resistance to fluoroquinolones and carbapenems in clinical P. putida isolates.

  16. Polyamines Inhibit Porin-Mediated Fluoroquinolone Uptake in Mycobacteria

    PubMed Central

    Sarathy, Jansy Passiflora; Lee, Edmund; Dartois, Véronique

    2013-01-01

    Polyamines decrease the permeability of the outer membrane of Escherichia coli to fluoroquinolones and β-lactams. In this study, we tested the effect of four polyamines (spermidine, spermine, cadaverine and putrescine) on fluoroquinolone uptake in Mycobacterium bovis BCG. Our results show that polyamines are also capable of reducing the permeability of the mycobacterial outer membrane to fluoroquinolones. Spermidine was most effective and demonstrated reversible dose- and pH-dependent inhibition of ciprofloxacin accumulation. The extent of this inhibition was demonstrated across the fluoroquinolone compound class to varying degrees. Furthermore, we have shown that the addition of spermidine increases the survival of M. bovis BCG after a 5-day exposure to ciprofloxacin by up to 25 times. The treatment of actively-replicating Mycobacterium tuberculosis with spermidine reduced ciprofloxacin accumulation by half while non-replicating nutrient-starved M. tuberculosis cultures lacked similar sensitivity to polyamines. Gene expression studies showed that several outer membrane proteins are significantly down–regulated during the shift to non–replication. Collectively, these characteristics of fluoroquinolone uptake in M. bovis BCG are consistent with facilitated transport by porin-like proteins and suggest that a reduction in intracellular uptake contributes to the phenotypic drug resistance demonstrated by M. tuberculosis in the non-replicating state. PMID:23755283

  17. Molecular mechanism of fluoroquinolones resistance in Mycoplasma hominis clinical isolates.

    PubMed

    Meng, Dong-Ya; Sun, Chang-Jian; Yu, Jing-Bo; Ma, Jun; Xue, Wen-Cheng

    2014-01-01

    To evaluate the molecular mechanism of fluoroquinolones resistance in Mycoplasma hominis (MH) clinical strains isolated from urogenital specimens. 15 MH clinical isolates with different phenotypes of resistance to fluoroquinolones antibiotics were screened for mutations in the quinolone resistance-determining regions (QRDRs) of DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE) in comparison with the reference strain PG21, which is susceptible to fluoroquinolones antibiotics. 15 MH isolates with three kinds of quinolone resistance phenotypes were obtained. Thirteen out of these quinolone-resistant isolates were found to carry nucleotide substitutions in either gyrA or parC. There were no alterations in gyrB and no mutations were found in the isolates with a phenotype of resistance to Ofloxacin (OFX), intermediate resistant to Levofloxacin (LVX) and Sparfloxacin (SFX), and those susceptible to all three tested antibiotics. The molecular mechanism of fluoroquinolone resistance in clinical isolates of MH was reported in this study. The single amino acid mutation in ParC of MH may relate to the resistance to OFX and LVX and the high-level resistance to fluoroquinolones for MH is likely associated with mutations in both DNA gyrase and the ParC subunit of topoisomerase IV.

  18. 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. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. The role of fluoroquinolones in the management of urinary tract infections in areas with high rates of fluoroquinolone-resistant uropathogens.

    PubMed

    Chen, Y-H; Ko, W-C; Hsueh, P-R

    2012-08-01

    Fluoroquinolones have been recommended as the drugs of choice for the empirical treatment of uncomplicated and complicated urinary tract infections (UTIs) caused by trimethoprim-sulfamethoxazole-resistant uropathogens. However, because of the increased use of both oral and parenteral fluoroquinolones for other kinds of infections, increasing rates of resistance to fluoroquinolones among the most common uropathogens have challenged this recommendation, particularly in the Asia-Pacific region. The current interpretative criteria for the in vitro susceptibility of uropathogens to some fluoroquinolones, such as levofloxacin and ciprofloxacin, are set according to their therapeutic efficacy for bloodstream infections, and are not specific to UTIs. Fluoroquinolones exhibit concentration-dependent antibacterial activity, high renal excretion, and relatively early and prolonged urinary bactericidal titers. Whether or not current interpretative criteria for the in vitro susceptibility of uropathogens to fluoroquinolones predict clinical failure in treating UTIs is still controversial. The Clinical and Laboratory Standards Institute (CLSI) has established UTI-specific breakpoints for resistance to a few fluoroquinolones. However, the application of high-dose fluoroquinolone therapy for the treatment of mild to moderate UTIs caused by isolates with higher minimum inhibitory concentrations (MICs) of several fluoroquinolones needs to be re-validated based on more relevant clinical studies, prudent pharmacokinetic/pharmacodynamic (PK/PD) considerations, and thorough study of the mutant prevention concentration of fluoroquinolones in the treatment of UTI.

  20. Fluoroquinolones in community-acquired pneumonia: guide to selection and appropriate use.

    PubMed

    Frei, Christopher R; Labreche, Matthew J; Attridge, Russell T

    2011-04-16

    Fluoroquinolone use has dramatically increased since the introduction of the first respiratory fluoroquinolone in the late 1990s. Over a relatively brief period of time, the respiratory fluoroquinolones have supplanted other first-line options as the predominant community-acquired pneumonia (CAP) therapy in hospitals. This article discusses the rise of the fluoroquinolone era, debates the comparative effectiveness of fluoroquinolones for CAP therapy, examines fluoroquinolone resistance and adverse drug reactions, and discusses new trends in pneumonia epidemiology and outcomes assessment. Overall, published data suggest that fluoroquinolone monotherapy is associated with improved patient survival compared with β-lactam monotherapy and similar survival to β-lactam plus macrolide combination therapy. Fluoroquinolone monotherapy may be associated with shorter hospital length of stay compared with β-lactam plus macrolide combination therapy, particularly in severe pneumonia or with high-dose therapy. There is insufficient evidence to conclude that any individual fluoroquinolone therapy is better than another with regards to patient mortality. Fluoroquinolones are generally well tolerated and Streptococcus pneumoniae resistance remains low; however, rare but serious adverse effects have been reported. Some members of the fluoroquinolone class have been removed from the market amidst safety concerns. Pneumonia classifications have changed and antipseudomonal fluoroquinolones may have a role in healthcare-associated pneumonia when administered in combination with other antipseudomonal and anti-methicillin-resistant Staphylococcus aureus therapies.

  1. Low rate of fluoroquinolone resistance in Mycobacterium tuberculosis isolates from northern Tanzania.

    PubMed

    van den Boogaard, Jossy; Semvua, Hadija H; van Ingen, Jakko; Mwaigwisya, Solomon; van der Laan, Tridia; van Soolingen, Dick; Kibiki, Gibson S; Boeree, Martin J; Aarnoutse, Rob E

    2011-08-01

    Fluoroquinolones are used in second-line treatment of tuberculosis (TB) and have a potential role in shortening TB treatment duration. The wide use of fluoroquinolones in the treatment of other infections, including respiratory tract infections in patients with (undiagnosed) active TB, could result in fluoroquinolone-resistant Mycobacterium tuberculosis. We determined the rate of fluoroquinolone resistance in M. tuberculosis isolates obtained from Tanzanian patients and linked this to previous fluoroquinolone exposure and mycobacterial resistance to rifampicin and isoniazid. A total of 291 M. tuberculosis isolates were obtained between April 2009 and June 2010 from patients with smear-positive pulmonary TB and tested for susceptibility to ciprofloxacin, moxifloxacin, rifampicin and isoniazid. Information on previous fluoroquinolone use was obtained by interviewing patients and checking their medical files. Only 2 (0.7%) of the 291 M. tuberculosis isolates were resistant to ciprofloxacin; 1 of which was intermediately resistant to moxifloxacin as well. These two isolates were susceptible to rifampicin and isoniazid. Twenty-two (8%) of the 291 patients had a history of fluoroquinolone use (median: 7 days; interquartile range: 5-10 days). The patients from whom the fluoroquinolone-resistant M. tuberculosis isolates were obtained had no known history of previous fluoroquinolone use. Our findings indicate that the rate of fluoroquinolone-resistant M. tuberculosis in Tanzanian patients with TB is low and not related to previous, brief episodes of exposure to fluoroquinolones. The findings favour future application of fluoroquinolones in TB treatment regimens of shorter duration.

  2. Reduction of fluoroquinolone use is associated with a decrease in methicillin-resistant Staphylococcus aureus and fluoroquinolone-resistant Pseudomonas aeruginosa isolation rates: a 10 year study.

    PubMed

    Lafaurie, Matthieu; Porcher, Raphael; Donay, Jean-Luc; Touratier, Sophie; Molina, Jean-Michel

    2012-04-01

    High rates of methicillin-resistant Staphylococcus aureus (MRSA) and fluoroquinolone-resistant Pseudomonas aeruginosa may be related, in part, to the overuse of fluoroquinolones. The objective was to analyse and correlate long-term surveillance data on MRSA and fluoroquinolone-resistant P. aeruginosa rates and antibiotic consumption after implementation of an institution-wide programme to reduce fluoroquinolone use. An interrupted time series/quasi-experimental study of monthly fluoroquinolone use and MRSA and fluoroquinolone-resistant P. aeruginosa isolation rates was carried out in a tertiary hospital during three periods: pre-intervention (January 2000-August 2005), intervention (September 2005-March 2006), and post-intervention (March 2006-March 2010). The effect of the intervention on the consumption of fluoroquinolones and bacterial resistance was assessed using segmented regression analyses. Mean monthly fluoroquinolone consumption dropped by 29.1 defined daily doses per 1000 patient-days (DDD/1000 PD) (95% CI 13.1-45.9; P = 0.0005) from a mean of 148.2 to 119.1 DDD/1000 PD during the intervention period. A sustained and significant decrease in fluoroquinolone consumption of -0.95 DDD/1000 PD/month was also observed during the post-intervention period (P = 0.0002). During the post-intervention period the rate of fluoroquinolone-resistant P. aeruginosa continuously decreased, from a mean of 42% to 26%, with a constant relative change rate of -13%/year (95% CI -19 to -5, P = 0.001). A decrease in the MRSA rate was observed during the intervention period, from a mean resistance rate of 27% to 21% (P < 0.0001). We showed the sustained impact of a fluoroquinolone control programme on the reduction of fluoroquinolone use with a significant decrease in fluoroquinolone-resistant P. aeruginosa and MRSA rates over 4 years.

  3. 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

  4. 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

  5. STO-2: Support for 4th Year Operations, Recovery, and Science (JPL co-I)

    NASA Astrophysics Data System (ADS)

    Kawamura, Jonathan

    Here we propose "STO-2: Support for 4th Year Operations, Recovery, and Science," a project being led by Dr. Christopher Walker of the University of Arizona. The Stratospheric TeraHertz Observatory was ready for its second Antarctic flight (STO-2) in the 2015-2016 austral summer. However, due to the late establishment of the stratospheric anti-cyclone and poor surface conditions, STO-2 was unable to launch. The decision was made to winter-over the STO-2 payload in its hangar for launch during the 2016-2017 Antarctic campaign. Funds to cover preparations and deployment of key members of the instrument team in support of the campaign are being provided by NASA under the existing grant. However, these funds are only sufficient to cover expenses up to December 31st, 2016. Here, we request resources for calendar year 2017 to support mission operations, payload recovery, and science operations. These elements will enable the team to deliver fully on STO-2's science mission, and maximize NASA's demonstrated investment in STO-2's success. STO-2 addresses a key problem in modern astrophysics: understanding the Life Cycle of the Interstellar Medium (ISM). STO-2 will survey approximately ˜ of the Southern Galactic Plane in the dominant interstellar cooling line [CII] (158 μm) and the important star formation tracer [NII] (205 μm). In addition, STO-2 will perform path finding observations of the 63 μm [OI] line toward selected regions. With 1 arcminute angular resolution, STO-2 will spatially resolve atomic, ionic and molecular clouds out to 10 kpc. The STO-2 survey will be conducted at unparalleled sensitivity levels. STO-2 will uniquely probe the pivotal formative and disruptive stages in the life cycle of interstellar clouds and the relationship between global star formation rates and the properties of the ISM. Combined with previous HI and CO surveys, STO-2 will create 3- dimensional maps of the structure, dynamics, turbulence, energy balance, and pressure of the Milky

  6. 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.

  7. Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever).

    PubMed

    Effa, Emmanuel E; Lassi, Zohra S; Critchley, Julia A; Garner, Paul; Sinclair, David; Olliaro, Piero L; Bhutta, Zulfiqar A

    2011-10-05

    Typhoid and paratyphoid are febrile illnesses, due to a bacterial infection, which remain common in many low- and middle-income countries. The World Health Organization (WHO) currently recommends the fluoroquinolone antibiotics in areas with known resistance to the older first-line antibiotics. To evaluate fluoroquinolone antibiotics for treating children and adults with enteric fever. We searched The Cochrane Infectious Disease Group Specialized Register (February 2011); Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library (2011, Issue 2); MEDLINE (1966 to February 2011); EMBASE (1974 to February 2011); and LILACS (1982 to February 2011). We also searched the metaRegister of Controlled Trials (mRCT) in February 2011. Randomized controlled trials examining fluoroquinolone antibiotics, in people with blood, stool or bone marrow culture-confirmed enteric fever. Two authors independently assessed the trial's methodological quality and extracted data. We calculated risk ratios (RR) for dichotomous data and mean difference for continuous data with 95% confidence intervals (CI).Comparative effectiveness has been interpreted in the context of; length of treatment, dose, year of study, known levels of antibiotic resistance, or proxy measures of resistance such as the failure rate in the comparator arm. Twenty-six studies, involving 3033 patients, are included in this review.Fluoroquinolones versus older antibiotics (chloramphenicol, co-trimoxazole, amoxicillin and ampicillin)In one study from Pakistan in 2003-04, high clinical failure rates were seen with both chloramphenicol and co-trimoxazole, although resistance was not confirmed microbiologically. A seven-day course of either ciprofloxacin or ofloxacin were found to be superior. Older studies of these comparisons failed to show a difference (six trials, 361 participants).In small studies conducted almost two decades ago, the fluoroquinolones were demonstrated to have fewer

  8. Insight view on possible role of fluoroquinolones in cancer therapy.

    PubMed

    Sharma, Prabodh C; Chaudhary, Monika; Sharma, Archana; Piplani, Mona; Rajak, Harish; Prakash, Om

    2013-08-01

    Cancer is a disease without limits turning out to be prime cause for raising death toll around the world. Several treatment strategies including chemotherapy, surgery and radiotherapy are being employed worldwide to combat this disease. Due to the unwanted effects of currently available therapies, scientific community is immensely interested in exploring newer alternative pathways. Fluoroquinolones have been employed as potent anti-microbial agents for last few decades and now being looked up as potential therapeutic agents in the other ailments also. Several research endeavours are carried out in different parts of the world to focus on the prospective role of fluoroquinolones in carcinogenesis and mutagenesis. This article is an earnest attempt to present recent research work carried out on fluoroquinolones in the context to cancer treatment therapies.

  9. Clinical and Histopathologic Features of Fluoroquinolone-Induced Liver Injury

    PubMed Central

    Orman, Eric S.; Conjeevaram, Hari S.; Vuppalanchi, Raj; Freston, James W.; Rochon, James; Kleiner, David E.; Hayashi, Paul H.

    2011-01-01

    Background & Aims Fluoroquinolone-induced liver injury is rare; no prospective studies of well-characterized case series have been published. We studied patients with fluoroquinolone-induced hepatoxicity, using data from the Drug-Induced Liver Injury Network (DILIN) to characterize injury patterns, outcomes, and associated features. Methods We identified subjects with fluoroquinolone hepatotoxicity who enrolled in the DILIN from September 2004 to January 2010. Demographic, clinical, and laboratory data were analyzed by descriptive statistical methods. Results Of the 679 registrants in the DILIN prospective study, 12 had hepatoxicity from fluoroquinolones (6 ciprofloxacin, 4 moxifloxacin, 1 levofloxacin, and 1 gatifloxacin). Seven were women; the median age was 57 years (range 23–80 years), and the median time from the start of fluoroquinolone therapy to symptoms was only 4 days (range 1–39 days). Nine cases developed symptoms on medication (2, 8, and 32 days after they stopped the medication, 3 patients each). Cases were equally distributed among hepatocellular injury (predominantly increased levels of alanine aminotransferase), cholestatic injury (predominantly increased levels of alkaline phosphatase [AP]), and both. Seven cases had immunoallergic features. Patients with mixed hepatocellular and cholestatic injury had mild disease without jaundice—all recovered. In contrast, 2 of 4 patients with hepatocellular injury and jaundice died, 1 of acute liver failure. One patient with cholestatic injury developed vanishing bile duct syndrome and required liver transplantation; another had a persistently increased serum level of AP. Conclusions Fluoroquinolone liver injury is rapid in onset and often has immunoallergic features, indicating a hypersensitivity reaction. The pattern of injury is can be hepatocellular, cholestatic, or mixed—mixed cases are the least severe. Acute and chronic liver failure can occur. PMID:21356330

  10. Working Group on Ice Forces (4th) State-of-the-Art Report Held in Iowa City, Iowa in 1986.

    DTIC Science & Technology

    1989-02-01

    OTTAWA OF CANADA CANADA HYDRAULICS LABORATORY Preface The following papers comprise the contributions to the 4 th State-of-the-Art Report on Ice Forces...in developing an understanding of ice interacting with offshore structures. : Odes iili/or AjA Jordaan and McKenna follow with a description of the...and Moore follow with a more detailed look at ice impact loads on ship hulls. This review is based on full scale trials of several icebreaking vessels

  11. Abstracts for the 4th Annual Congress on Medicine & Science in Ultra-Endurance Sports, May 30, 2017, Denver, Colorado.

    PubMed

    2017-04-01

    The 4th Annual Congress on Medicine & Science in Ultra-Endurance Sports will be held on May 30, 2017, in Denver, Colorado. While prior meetings have been multiple-day events, the 2017 Congress will be an intense 1-day preconference to the American College of Sports Medicine annual meeting. Details of this Congress, as well as past and future meetings, can be found at the Ultra Sports Science Foundation Web site: http://ultrasportsscience.us.

  12. 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.

  13. 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.

  14. Primary photoprocesses in a fluoroquinolone antibiotic sarafloxacin.

    PubMed

    Lorenzo, Fernando; Navaratnam, Suppiah; Edge, Ruth; Allen, Norman S

    2009-01-01

    The photophysical properties of the fluoroquinolone antibiotic sarafloxacin (SFX) were investigated in aqueous media. SFX in water, at pH 7.4, shows intense absorption with peaks at 272, 322 and 335 nm, (epsilon=36800 and 17000 dm3 mol(-1) cm(-1), respectively). Both the absorption and emission properties of SFX are pH-dependent; pKa values for the protonation equilibria of both the ground (5.8 and 9.1) and excited singlet states (5.7 and 9.0) of SFX were determined spectroscopically. SFX fluoresces weakly, the quantum yield for fluorescence emission being maximum (0.07) at pH 8. Laser flash photolysis and pulse radiolysis studies have been carried out in order to characterize the transient species of SFX in aqueous solution. Triplet-triplet absorption has a maximum at 610 nm with a molar absorption coefficient of 17,000+/-1000 dm3 mol(-1) cm(-1). The quantum yield of triplet formation has been determined to be 0.35+/-0.05. In the presence of oxygen, the triplet reacts to form excited singlet oxygen with quantum yield of 0.10. The initial triplet (3A*) was found to react with phosphate buffer to form triplet 3B* with lower energy and longer lifetime and having an absorption band centered at 700 nm. SFX triplet was also found to oxidize tryptophan to its radical with concomitant formation of the anion radical of SFX. Hence the photosensitivity of SFX could be initiated by the oxygen radicals and/or by SFX radicals acting as haptens.

  15. Inhibition of photosynthesis by a fluoroquinolone antibiotic.

    PubMed

    Aristilde, Ludmilla; Melis, Anastasios; Sposito, Garrison

    2010-02-15

    Recent microcosm studies have revealed that fluoroquinolone (FQ) antibiotics can have ecotoxicological impacts on photosynthetic organisms, but little is known about the mechanisms of toxicity. We employed a combination of modeling and experimental techniques to explore how FQs may have these unintended secondary toxic effects. Structure-activity analysis revealed that the quinolone ring and secondary amino group typically present in FQ antibiotics may mediate their action as quinone site inhibitors in photosystem II (PS-II), a key enzyme in photosynthetic electron transport. Follow-up molecular simulations involving nalidixic acid (Naldx), a nonfluorinated quinolone with a demonstrated adverse impact on photosynthesis, and ciprofloxacin (Cipro), the most commonly used FQ antibiotic, showed that both may interfere stereochemically with the catalytic activity of reaction center II (RC-II), the pheophytin-quinone-type center present in PS-II. Naldx can occupy the same binding site as the secondary quinone acceptor (Q(B)) in RC-II and interact with amino acid residues required for the enzymatic reduction of Q(B). Cipro binds in a somewhat different manner, suggesting a different mechanism of interference. Fluorescence induction kinetics, a common method of screening for PS-II inhibition, recorded for photoexcited thylakoid membranes isolated from Cipro-exposed spinach chloroplasts, indicated that Cipro interferes with the transfer of energy from excited antenna chlorophyll molecules to the reaction center in RC-II ([Cipro] >or= 5 microM in vitro and >or=10 microM in vivo) and thus delays the kinetics of photoreduction of the primary quinone acceptor (Q(A); [Cipro] >or= 0.6 microM in vitro). Spinach plants exposed to Cipro exhibited severe growth inhibition characterized by a decrease in both the synthesis of leaves and growth of the roots ([Cipro] >or= 0.5 microM in vivo). Our results thus demonstrate that Cipro and related FQ antibiotics may interfere with

  16. 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.

  17. Spectrofluorimetric determination of fluoroquinolones in pharmaceutical preparations

    NASA Astrophysics Data System (ADS)

    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.

  18. Appropriate use of fluoroquinolones in children.

    PubMed

    Principi, Nicola; Esposito, Susanna

    2015-04-01

    With the increasing resistance to antibiotics among common bacterial pathogens, challenges associated with the use of fluoroquinolones (FQs) in paediatrics have emerged. The majority of FQs have favourable pharmacokinetic properties, although these properties can differ in children compared with adults. Moreover, all FQs have broad antimicrobial activity both against Gram-positive and Gram-negative bacteria. However, only some FQs for which adequate studies are available have been approved for use in children in a limited number of clinical situations owing to the supposed risk of development of severe musculoskeletal disorders, as demonstrated in juvenile animals. Recent short- and long-term evaluations appear to indicate that, at least for levofloxacin, this risk, if present at all, is marginal. This marginal risk could lead to more frequent use of FQs in children, even to treat diseases for which several other drugs with documented efficacy, safety and tolerability are considered the first-line antibiotics. However, for most of the FQs, adequate long-term studies of safety are not available. This indicates that the use of FQs should be limited to selected respiratory infections (including tuberculosis), exacerbation of lung disease in cystic fibrosis, central nervous system infections, enteric infections, febrile neutropenia, as well as serious infections attributable to FQ-susceptible pathogen(s) in children with life-threatening allergies to alternative agents. When considering diseases that could benefit from the use of FQs, particular attention must be paid to the choice of drug and its dosage, considering that not all of the FQs have been evaluated in different diseases.

  19. Toxicity of fluoroquinolone antibiotics to aquatic organisms.

    PubMed

    Robinson, April A; Belden, Jason B; Lydy, Michael J

    2005-02-01

    Toxicity tests were performed with seven fluoroquinolone antibiotics, ciprofloxacin, lomefloxacin, ofloxacin, levofloxacin, clinafloxacin, enrofloxacin, and flumequine, on five aquatic organisms. Overall toxicity values ranged from 7.9 to 23,000 microg/L. The cyanobacterium Microcystis aeruginosa was the most sensitive organism (5-d growth and reproduction, effective concentrations [EC50s] ranging from 7.9 to 1,960 microg/L and a median of 49 microg/L), followed by duckweed (Lemna minor, 7-d reproduction, EC50 values ranged from 53 to 2,470 microg/L with a median of 106 microg/L) and the green alga Pseudokirchneriella subcapitata (3-d growth and reproduction, EC50 values ranged from 1,100 to 22,700 microg/L with a median 7,400 microg/L). Results from tests with the crustacean Daphnia magna (48-h survival) and fathead minnow (Pimephales promelas, 7-d early life stage survival and growth) showed limited toxicity with no-observed-effect concentrations at or near 10 mg/L. Fish dry weights obtained in the ciprofloxacin, levofloxacin, and ofloxacin treatments (10 mg/L) were significantly higher than in control fish. The hazard of adverse effects occurring to the tested organisms in the environment was quantified by using hazard quotients. An estimated environmental concentration of 1 microg/L was chosen based on measured environmental concentrations previously reported in surface water; at this level, only M. aeruginosa may be at risk in surface water. However, the selective toxicity of these compounds may have implications for aquatic community structure.

  20. Association between oral fluoroquinolone use and retinal detachment.

    PubMed

    Pasternak, Björn; Svanström, Henrik; Melbye, Mads; Hviid, Anders

    2013-11-27

    A recent study of ophthalmologic patients found a strong association between fluoroquinolone use and retinal detachment. Given the prevalent use of fluoroquinolones, this could, if confirmed in the general population, translate to many excess cases of retinal detachment that are potentially preventable. To investigate if oral fluoroquinolone use is associated with an increased risk of retinal detachment. A nationwide, register-based cohort study in Denmark from 1997 through 2011, using linked data on participant characteristics, filled prescriptions, and cases of retinal detachment with surgical treatment (scleral buckling, vitrectomy, or pneumatic retinopexy). The cohort included 748,792 episodes of fluoroquinolone use (660,572 [88%] ciprofloxacin) and 5,520,446 control episodes of nonuse. Poisson regression was used to estimate rate ratios (RRs) for incident retinal detachment, adjusting for a propensity score that included a total of 21 variables. The risk windows were classified as current use (days 1-10 from start of treatment), recent use (days 11-30), past use (days 31-60), and distant use (days 61-180). A total of 566 cases of retinal detachment occurred, of which 465 (82%) were rhegmatogenous detachments; 72 in fluoroquinolone users and 494 in control nonusers. The crude incidence rate was 25.3 cases per 100,000 person-years in current users, 18.9 in recent users, 26.8 in past users, and 24.8 in distant users compared with 19.0 in nonusers. Compared with nonuse, fluoroquinolone use was not associated with a significantly increased risk of retinal detachment: the adjusted RRs were 1.29 (95% CI, 0.53 to 3.13) for current use; 0.97 (95% CI, 0.46 to 2.05) for recent use; 1.37 (95% CI, 0.80 to 2.35) for past use; and 1.27 (95% CI, 0.93 to 1.75) for distant use. The absolute risk difference, estimated as the adjusted number of retinal detachment cases per 1,000,000 treatment episodes, was 1.5 (95% CI, -2.4 to 11.1) for current use. In this cohort study based on

  1. Fluoroquinolone antibacterials: a review on chemistry, microbiology and therapeutic prospects.

    PubMed

    Sharma, Prabodh Chander; Jain, Ankit; Jain, Sandeep

    2009-01-01

    Fluoroquinolones are one of the most promising and vigorously pursued areas of contemporary antiinfective chemotherapy depicting broad spectrum and potent activity. They have a relatively simple molecular nucleus, which is amenable to many structural modifications. These agents have several favorable properties such as excellent bioavailability, good tissue penetrability and a relatively low incidence of adverse and toxic effects. They have been found effective in treatment of various infectious diseases. This paper is an attempt to review the therapeutic prospects of fluoroquinolone antibacterials with an updated account on their development and usage.

  2. Fluoroquinolones in pediatrics and their nephrotoxicity in adults: minireview.

    PubMed

    Fanos, V; Cuzzolin, L

    2000-06-01

    In recent years there is increasing pressure to use fluoroquinolones in pediatric patients but relatively few data have been published in the literature. Therefore this paper reviews the available information about the pharmacokinetics of fluoroquinolones in children and their use in pediatric urinary tract infections, taking into account their potential as nephrotoxic agents. From the available data it seems reasonable to suggest that there is no risk of quinolone-induced nephrotoxicity and that this class of antibiotics may therefore be considered as potential candidates in urinary tract infections in children. Nevertheless adequate pharmacokinetic investigations and further studies on long-term monitoring for potential toxicity need to be conducted in pediatric populations.

  3. 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.

  4. Cotrimoxazole treats fluoroquinolone-resistant Salmonella typhi H58 infection.

    PubMed

    Karki, Manan; Pandit, Sarbagya; Baker, Stephen; Basnyat, Buddha

    2016-10-26

    A woman aged 20 years presented with fever and no localising signs. She was treated with cotrimoxazole and the subsequent blood culture was positive for Salmonella typhi (S. typhi), which was resistant to fluoroquinolones but susceptible to cotrimoxazole. Genotyping identified an FQ-R subclade of H58 S. typhi Fever clearance time was 4 days after starting the antibiotics, and no relapses were noted on 2 months of follow-up. This inexpensive, well-known and easily available antimicrobial could be suitably redeployed for fluoroquinolone-resistant enteric fever in South Asia.

  5. Anionic fluoroquinolones as antibacterials against biofilm-producing Pseudomonas aeruginosa.

    PubMed

    Long, Timothy E; Keding, Lexie C; Lewis, Demetria D; Anstead, Michael I; Withers, T Ryan; Yu, Hongwei D

    2016-02-15

    Pseudomonas aeruginosa is a common biofilm-forming bacterial pathogen implicated in diseases of the lungs. The extracellular polymeric substances (EPS) of respiratory Pseudomonas biofilms are largely comprised of anionic molecules such as rhamnolipids and alginate that promote a mucoid phenotype. In this Letter, we examine the ability of negatively-charged fluoroquinolones to transverse the EPS and inhibit the growth of mucoid P. aeruginosa. Anionic fluoroquinolones were further compared with standard antibiotics via a novel microdiffusion assay to evaluate drug penetration through pseudomonal alginate and respiratory mucus from a patient with cystic fibrosis.

  6. 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.

  7. [Fluoroquinolones in ophthalmology: mechanisms of action and resistance].

    PubMed

    Labetoulle, M; Chiquet, C

    2008-10-01

    The arrival of fluoroquinolones in the 1980s aroused enormous enthusiasm in the medical community, justified by the spectrum of antibacterial activity, good tolerance, and wide distribution in tissues, even after oral administration. However, the extensive use of these new antibiotiques finally ended in emerging resistance, which limits the efficiency of all the molecules in the class, including those that have appeared in the last few years. Ocular diseases also benefited from the emergence of fluoroquinolones, notably for topical treatments. It is now mandatory to adapt the prescriptions to the best indications, in order to protect the vast therapeutic potential of these molecules.

  8. In Vitro Activities of Six New Fluoroquinolones against Brucella melitensis

    PubMed Central

    Trujillano-Martín, Ignacio; García-Sánchez, Enrique; Martínez, Isaías Montes; Fresnadillo, María José; García-Sánchez, José Elías; García-Rodríguez, JoséÁngel

    1999-01-01

    We have tested the in vitro activities of eight fluoroquinolones against 160 Brucella melitensis strains. The most active was sitafloxacin (MIC at which 90% of the isolates are inhibited [MIC90], 0.12 μg/ml). In decreasing order, the activities (MIC90s) of the rest of the tested fluoroquinolones were as follows: levofloxacin, 0.5 μg/ml; ciprofloxacin, trovafloxacin, and moxifloxacin, 1 μg/ml; and ofloxacin, grepafloxacin, and gatifloxacin, 2 μg/ml. PMID:9869594

  9. Complete set of invariants of a 4th order tensor: the 12 tasks of HARDI from ternary quartics.

    PubMed

    Papadopoulo, Théo; Ghosh, Aurobrata; Deriche, Rachid

    2014-01-01

    Invariants play a crucial role in Diffusion MRI. In DTI (2nd order tensors), invariant scalars (FA, MD) have been successfully used in clinical applications. But DTI has limitations and HARDI models (e.g. 4th order tensors) have been proposed instead. These, however, lack invariant features and computing them systematically is challenging. We present a simple and systematic method to compute a functionally complete set of invariants of a non-negative 3D 4th order tensor with respect to SO3. Intuitively, this transforms the tensor's non-unique ternary quartic (TQ) decomposition (from Hilbert's theorem) to a unique canonical representation independent of orientation - the invariants. The method consists of two steps. In the first, we reduce the 18 degrees-of-freedom (DOF) of a TQ representation by 3-DOFs via an orthogonal transformation. This transformation is designed to enhance a rotation-invariant property of choice of the 3D 4th order tensor. In the second, we further reduce 3-DOFs via a 3D rotation transformation of coordinates to arrive at a canonical set of invariants to SO3 of the tensor. The resulting invariants are, by construction, (i) functionally complete, (ii) functionally irreducible (if desired), (iii) computationally efficient and (iv) reversible (mappable to the TQ coefficients or shape); which is the novelty of our contribution in comparison to prior work. Results from synthetic and real data experiments validate the method and indicate its importance.

  10. Required and Elective Experiences During the 4th Year: An Analysis of ACGME Accredited Psychiatry Residency Program Websites.

    PubMed

    Vestal, Heather S; Belitsky, Richard; Bernstein, Carol A; Chaukos, Deanna; Cohen, Mitchell B; Dickstein, Leah J; Hilty, Donald M; Hutner, Lucy; Sakman, Ferda; Scheiber, Stephen C; Wrzosek, Marika I; Silberman, Edward K

    2016-10-01

    The objective of this study was to assess and describe required and elective components of the 4th post-graduate year (PGY4) in psychiatry residency programs. We reviewed the websites of all 193 2014-2015 ACGME accredited psychiatry residency programs for content describing the specific components of the PGY4 year. Nearly all residency programs (99 %) had some form of required experiences during the PGY4 year. Ninety-four percent had clinical requirements for PGY4 residents, with longitudinal outpatient clinic being the most common (77 %). All programs offered some elective time during PGY4, but the amount of time ranged from 2 months to 100 %. Virtually all residency programs include some requirements in the 4th year (most commonly didactics and outpatient clinic) in addition to a broad array of elective experiences. Although 3 years may suffice for residents to complete ACGME requirements, a variety of factors may motivate programs to include required 4th year curricula. Future studies should explore the rationales for and possible benefits of programmatic requirements throughout 4 versus only 3 years of psychiatric training.

  11. Kidney retransplantation from HLA incompatible living donors: a single centre study of 3(rd) /4(th) transplants.

    PubMed

    Barnes, J C H; Goodyear, S J; Imray, C E A; Lam, F T; Kashi, S H; Tan, L C; Higgins, R; Imray, C H E

    2017-09-04

    The demand for kidney retransplantation following graft failure is rising. Repeat transplantation is often associated with poorer outcomes due to both immunological and surgical challenges. The aim of this study was to compare surgical and functional outcomes of kidney retransplantation in recipients that had previously had at least 2 kidney transplants with a focus on those with antibody incompatibility. We analysed 66 patients who underwent renal transplantation at a single centre between 2003 and 2011. Consecutive patients receiving their 3(rd) or 4(th) kidney were case-matched with an equal number of 1(st) and 2(nd) transplants. Twenty-two 3(rd) and 4(th) kidney transplants were matched with 22 first and 22 second transplants. Operative times and length of stay were equivalent between the subgroups. Surgical complication rates were similar in all groups (22.7% in 1(st) and 2(nd) transplants, and 27.2% in 3(rd) /4(th) transplants). There was no significant difference in patient or graft survival over 5 years. Graft function was similar between transplant groups at 1, 3 and 5 years. Third and fourth kidney transplants can be performed safely with similar outcomes to 1(st) and 2(nd) transplants. Kidney retransplantation from antibody incompatible donors may be appropriate for highly sensitised patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  12. Evaluation of an intervention designed to decrease the rate of nosocomial methicillin-resistant Staphylococcus aureus infection by encouraging decreased fluoroquinolone use.

    PubMed

    Madaras-Kelly, Karl J; Remington, Richard E; Lewis, Pamela G; Stevens, Dennis L

    2006-02-01

    Society for Health Care Epidemiology guidelines recommend decreasing the use of fluoroquinolone antibiotics in institutions where methicillin-resistant Staphylococcus aureus (MRSA) is endemic. We evaluated whether an intervention to limit fluoroquinolone use was associated with a lower rate of nosocomial MRSA infection and summarized changes in antibiotic use, changes in other variables potentially correlated with a lower rate of MRSA infection, and rates of nosocomial infections due to other pathogens. Single-center quasi-experimental design. A time series of nosocomial MRSA infections was measured at monthly intervals from July 2001 through June of 2004; there were 80 MRSA infections recorded. Segmented regression analysis (ie, quasi-Poisson generalized linear models) was used to evaluate variables possibly associated with the nosocomial MRSA infection rate. An 87-bed Veterans Affairs teaching hospital with an extended-care facility. A physician-directed computer-generated intervention designed to limit the use of fluoroquinolone antibiotics was initiated, and institutional changes in antibiotic use and nosocomial MRSA infection rates were tracked. After the intervention, fluoroquinolone use decreased by approximately 34%, and levofloxacin use decreased by approximately 50%. Decreased fluoroquinolone use was offset by increased cephalosporin, piperacillin-tazobactam, and trimethoprim-sulfamethoxazole use. The nosocomial MRSA infection rate decreased from 1.37 to 0.63 episodes per 1,000 patient-days after the study intervention (P=.02). Coagulase-negative Staphylococcus and Enterococcus infection rates also decreased. However, the rate of infection with gram-negative organisms increased. The rate of MRSA infection was positively correlated with levofloxacin use (P=.01) and azithromycin use (P=.08), whereas it was negatively correlated with summer season (P=.05). In a subsequent model, the rate of MRSA infection was negatively correlated with the study intervention

  13. High-Level Fluoroquinolone Resistance in Ophthalmic Clinical Isolates Belonging to the Species Corynebacterium macginleyi▿

    PubMed Central

    Eguchi, Hiroshi; Kuwahara, Tomomi; Miyamoto, Tatsuro; Nakayama-Imaohji, Haruyuki; Ichimura, Minoru; Hayashi, Tetsuya; Shiota, Hiroshi

    2008-01-01

    The clinical importance of nondiphtherial Corynebacterium, a ubiquitous member of the normal human microflora of the skin and mucous membrane, for ocular surface infections has been recognized recently. We performed an antimicrobial susceptibility test with Etest strips for three fluoroquinolones (ciprofloxacin, norfloxacin, and levofloxacin) and a taxonomic analysis on 21 isolates of Corynebacterium from ophthalmic samples. Of these, 16 isolates were identified as C. macginleyi at the species level on the basis of 16S rRNA gene sequence comparisons. The remaining five isolates were determined to be C. mastitidis (four) or C. accolens (one). Eleven of the C. macginleyi isolates showed high levels of resistance to all of the fluoroquinolones tested, and one isolate was resistant to norfloxacin alone. An analysis of the amplified quinolone-resistance-determining regions of the gyrA genes revealed that a single amino acid substitution in position 83 of the gyrA product was sufficient to generate the norfloxacin resistance phenotype, and double mutations leading to amino acid changes in positions 83 and 87 were necessary for high-level resistance against the other fluoroquinolones. We conducted the first example of multilocus sequence typing (MLST) analysis on C. macginleyi. The MLST analysis grouped the majority of C. macginleyi isolates into a single lineage, and another molecular strain typing by random amplified polymorphic DNA fragment patterns supported the finding, indicating that a particular lineage of C. macginleyi is dominant on the human ocular surface. This type of population might be particularly adaptable to the milieu on the human ocular surface. PMID:18077650

  14. Call for the international adoption of microbiological breakpoints for fluoroquinolones and Streptococcus pneumoniae.

    PubMed

    Schurek, Kristen N; Adam, Heather J; Hoban, Daryl J; Zhanel, George G

    2006-09-01

    The use of current Clinical and Laboratory Standards Institute levofloxacin breakpoints for assessing fluoroquinolone resistance in Streptococcus pneumoniae is inadequate for detecting isolates possessing first-step parC mutations. Consequently, the risk for development of fluoroquinolone resistance is greatly underestimated. Adopting microbiological breakpoints for fluoroquinolones and S. pneumoniae, where parC mutations are rare in susceptible isolates, more accurately describes the emergence of resistance and may help to prevent a number of future fluoroquinolone treatment failures. Additionally, we propose that the use of a second fluoroquinolone marker, such as ciprofloxacin, offers the best prediction for detecting an isolate possessing a first-step parC mutation.

  15. Population-based resistance of Mycobacterium tuberculosis isolates to pyrazinamide and fluoroquinolones: results from a multicountry surveillance project.

    PubMed

    Zignol, Matteo; Dean, Anna S; Alikhanova, Natavan; Andres, Sönke; Cabibbe, Andrea Maurizio; Cirillo, Daniela Maria; Dadu, Andrei; Dreyer, Andries; Driesen, Michèle; Gilpin, Christopher; Hasan, Rumina; Hasan, Zahra; Hoffner, Sven; Husain, Ashaque; Hussain, Alamdar; Ismail, Nazir; Kamal, Mostofa; Mansjö, Mikael; Mvusi, Lindiwe; Niemann, Stefan; Omar, Shaheed V; Qadeer, Ejaz; Rigouts, Leen; Ruesch-Gerdes, Sabine; Schito, Marco; Seyfaddinova, Mehriban; Skrahina, Alena; Tahseen, Sabira; Wells, William A; Mukadi, Ya Diul; Kimerling, Michael; Floyd, Katherine; Weyer, Karin; Raviglione, Mario C

    2016-10-01

    Pyrazinamide and fluoroquinolones are essential antituberculosis drugs in new rifampicin-sparing regimens. However, little information about the extent of resistance to these drugs at the population level is available. In a molecular epidemiology analysis, we used population-based surveys from Azerbaijan, Bangladesh, Belarus, Pakistan, and South Africa to investigate resistance to pyrazinamide and fluoroquinolones among patients with tuberculosis. Resistance to pyrazinamide was assessed by gene sequencing with the detection of resistance-conferring mutations in the pncA gene, and susceptibility testing to fluoroquinolones was conducted using the MGIT system. Pyrazinamide resistance was assessed in 4972 patients. Levels of resistance varied substantially in the surveyed settings (3·0-42·1%). In all settings, pyrazinamide resistance was significantly associated with rifampicin resistance. Among 5015 patients who underwent susceptibility testing to fluoroquinolones, proportions of resistance ranged from 1·0-16·6% for ofloxacin, to 0·5-12·4% for levofloxacin, and 0·9-14·6% for moxifloxacin when tested at 0·5 μg/mL. High levels of ofloxacin resistance were detected in Pakistan. Resistance to moxifloxacin and gatifloxacin when tested at 2 μg/mL was low in all countries. Although pyrazinamide resistance was significantly associated with rifampicin resistance, this drug may still be effective in 19-63% of patients with rifampicin-resistant tuberculosis. Even though the high level of resistance to ofloxacin found in Pakistan is worrisome because it might be the expression of extensive and unregulated use of fluoroquinolones in some parts of Asia, the negligible levels of resistance to fourth-generation fluoroquinolones documented in all survey sites is an encouraging finding. Rational use of this class of antibiotics should therefore be ensured to preserve its effectiveness. Bill & Melinda Gates Foundation, United States Agency for International Development

  16. Fluoroquinolones for treating tuberculosis (presumed drug-sensitive).

    PubMed

    Ziganshina, Lilia E; Titarenko, Albina F; Davies, Geraint R

    2013-06-06

    Currently the World Health Organization only recommend fluoroquinolones for people with presumed drug-sensitive tuberculosis (TB) who cannot take standard first-line drugs. However, use of fluoroquinolones could shorten the length of treatment and improve other outcomes in these people. This review summarises the effects of fluoroquinolones in first-line regimens in people with presumed drug-sensitive TB. To assess fluoroquinolones as substitute or additional components in antituberculous drug regimens for drug-sensitive TB. We searched the Cochrane Infectious Diseases Group Specialized Register; CENTRAL (The Cochrane Library 2013, Issue 1); MEDLINE; EMBASE; LILACS; Science Citation Index; Databases of Russian Publications; and metaRegister of Controlled Trials up to 6 March 2013. Randomized controlled trials (RCTs) of antituberculous regimens based on rifampicin and pyrazinamide and containing fluoroquinolones in people with presumed drug-sensitive pulmonary TB. Two authors independently applied inclusion criteria, assessed the risk of bias in the trials, and extracted data. We used the risk ratio (RR) for dichotomous data and the fixed-effect model when it was appropriate to combine data and no heterogeneity was present. We assessed the quality of evidence using the GRADE approach. We identified five RCTs (1330 participants) that met the inclusion criteria. None of the included trials examined regimens of less than six months duration. Fluoroquinolones added to standard regimensA single trial (174 participants) added levofloxacin to the standard first-line regimen. Relapse and treatment failure were not reported. For death, sputum conversion, and adverse events we are uncertain if there is an effect (one trial, 174 participants, very low quality evidence for all three outcomes). Fluoroquinolones substituted for ethambutol in standard regimens Three trials (723 participants) substituted ethambutol with moxifloxacin, gatifloxacin, and ofloxacin into the standard

  17. Killing Two Birds with One Stone: Improving 4th Year Student Teachers' Teaching Skills and Preparing 1st Year Student Teachers for Teaching Practice

    ERIC Educational Resources Information Center

    Saka, Ahmet Zeki; Saka, Arzu

    2004-01-01

    The aim of this study is to develop a new approach to help both 4th year students and 1st year students to get the utmost benefit from application activities. This new approach will provide 4th year students with an experience of teaching practice and also preparation of 1st student teachers to teaching practice process before they start their…

  18. 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

  19. Genome-wide transcriptome analysis of fluoroquinolone resistance in clinical isolates of Escherichia coli.

    PubMed

    Yamane, Takashi; Enokida, Hideki; Hayami, Hiroshi; Kawahara, Motoshi; Nakagawa, Masayuki

    2012-04-01

    Coincident with their worldwide use, resistance to fluoroquinolones in Escherichia coli has increased. To identify the gene expression profiles underlying fluoroquinolone resistance, we carried out genome-wide transcriptome analysis of fluoroquinolone-sensitive E. coli. Four fluoroquinolone-sensitive E. coli and five fluoroquinolone-resistant E. coli clinical isolates were subjected to complementary deoxyribonucleic acid microarray analysis. Some upregulated genes' expression was verified by real-time polymerase chain reaction using 104 E. coli clinical isolates, and minimum inhibitory concentration tests were carried out by using their transformants. A total of 40 genes were significantly upregulated in fluoroquinolone-resistant E. coli isolates (P < 0.05). The expression of phage shock protein operons, which are involved in biofilm formation, was markedly upregulated in our profile of fluoroquinolone-resistant E. coli. One of the phage shock protein operons, pspC, was significantly upregulated in 50 fluoroquinolone-resistant E. coli isolates (P < 0.0001). The expression of type I fimbriae genes, which are pilus operons involved in biofilm formation, were markedly downregulated in fluoroquinolone-resistant E. coli. Deoxyribonucleic acid adenine methyltransferase (dam), which represses type I fimbriae genes, was significantly upregulated in the clinical fluoroquinolone-resistant E. coli isolates (P = 0.007). We established pspC- and dam-expressing E. coli transformants from fluoroquinolone-sensitive E. coli, and the minimum inhibitory concentration tests showed that the transformants acquired fluoroquinolone resistance, suggesting that upregulation of these genes contributes to acquiring fluoroquinolone resistance. Upregulation of psp operones and dam underlying pilus operons downregulation might be associated with fluoroquinolone resistance in E. coli. © 2011 The Japanese Urological Association.

  20. Effects of fluoroquinolones on the locomotor activity in rats.

    PubMed

    Thiel, R; Metzner, S; Gericke, C; Rahm, U; Stahlmann, R

    2001-03-01

    During therapy with fluoroquinolones adverse CNS reactions such as dizziness, light-headedness, insomnia or sleepiness are observed in up to 20% of patients. Using a device developed at our institute for the simultaneous registration of the activity of rats housed in single cages, we have investigated the effects of trovafloxacin, fleroxacin or ofloxacin on the locomotor activity of juvenile and adult rats (11 per group) after oral administration of 600 mg/kg for 5 consecutive days. The effects were most pronounced after fleroxacin, which induced a reduction in activity to 36 +/- 9% (mean +/- SD) of the values measured in juvenile rats before treatment and to 60 +/- 21% (mean +/- SD) in adult rats. HPLC analysis of the plasma concentrations in juvenile rats showed that the concentrations of trovafloxacin were considerably lower than those of the other fluoroquinolones that had been studied previously in our laboratory: the peak concentration of trovafloxacin was 14 +/- 2.9 mg/l (mean +/- SD) after a single dose of 600 mg/kg in juvenile rats. Overall, we showed that the locomotor activities of juvenile and adult rats were significantly depressed during treatment with fluoroquinolones. The effects were more pronounced in juveniles. Monitoring of the locomotor activity of rats is a suitable approach to study CNS effects of fluoroquinolones in animals, but pharmacokinetics have to be taken into account.

  1. In vitro selection of fluoroquinolone resistance in Brucella melitensis.

    PubMed

    Ravanel, N; Gestin, B; Maurin, M

    2009-07-01

    Moxifloxacin-resistant mutants of Brucella melitensis 16M [moxifloxacin minimum inhibitory concentration (MIC)=1mg/L] were selected in order to characterise fluoroquinolone resistance mechanisms in this species. Eight independent mutants were obtained, with moxifloxacin MICs of 16-32mg/L. The mutants displayed variable cross-resistance levels to other fluoroquinolone compounds, but no increased resistance to aminoglycosides, tetracycline, rifampicin, macrolides or co-trimoxazole. Sequencing of type II topoisomerase-encoding genes (gyrA, gyrB, parC and parE), which are natural targets for fluoroquinolones, revealed a gyrA mutation leading to the amino acid substitution Ala83Val (Escherichia coli numbering system) in five mutants with a moxifloxacin MIC of 32mg/L, whereas no mutation was found in the remaining three mutants with a MIC of 16mg/L. Phenylalanine-arginine-beta-naphthylamide dihydrochloride, an efflux pump inhibitor, reduced moxifloxacin MICs by a factor of two to eight in all resistant mutants. In B. melitensis, fluoroquinolone resistance may arise from gyrA mutation and efflux pump overexpression mechanisms.

  2. Sorption of fluoroquinolones and sulfonamides in 13 Brazilian soils.

    PubMed

    Leal, Rafael Marques Pereira; Alleoni, Luis Reynaldo Ferracciú; Tornisielo, Valdemar Luiz; Regitano, Jussara Borges

    2013-08-01

    Animal production is a leading economic activity in Brazil and antibiotics are widely used. However, the occurrence, behavior, and impacts of antibiotics in Brazilian soils are still poorly known. We evaluated the sorption behavior of four fluoroquinolones (norfloxacin, ciprofloxacin, danofloxacin, and enrofloxacin) and five sulfonamides (sulfadiazine, sulfachloropyridazine, sulfamethoxazole, sulfadimidine, and sulfathiazole) in 13 Brazilian soils with contrasting physical, chemical, and mineralogical properties. Fluoroquinolone sorption was very high (Kd≥544 L kg(-1)) whereas sulfonamide sorption ranged from low to high (Kd=0.7-70.1 L kg(-1)), consistent with previous reports in the literature. Soil texture and cation exchange capacity were the soil attributes that most affected sorption. Cation exchange was the most important sorption mechanism for the fluoroquinolones in highly weathered tropical soils, although cation bridging and ion pairing could not be ruled out. Hydrophobic partition played an important role in the sorption of the sulfonamides, but sorption was also affected by non-hydrophobic interactions with organic and/or mineral surfaces. Sorption for both compound classes tended to be higher in soils with high Al and Fe oxihydroxide contents, but they were not correlated with Kd values. No direct effect of soil pH was seen. The fluoroquinolones are not expected to leach even in worst-case scenarios (soils rich in sand and poor in organic carbon), whereas soil attributes dictate leaching potential for the sulfonamides. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. The chemical and biological aspects of fluoroquinolones: reality and dreams.

    PubMed

    Bhanot, S K; Singh, M; Chatterjee, N R

    2001-03-01

    A vast array of fluoroquinolones having excellent broad-spectrum activity form an invaluable part of the present anti-infective armory of the clinicians. A number of these compounds are today's blockbusters of the antibacterial market due to their therapeutic efficacy having tolerable side effects and thus challenging the predominance of well established beta-lactam antibiotics which are becoming more prone to the resistant pathogenic bacteria. Since the discovery of nalidixic acid the development of fluoroquinolones has experienced an exponential growth and is being continued with more vigor to obtain better drugs having multifunctional action. This article attempts to review the current developments of the chemical and biological aspects of fluoroquinolones in a chronological manner touching upon their antibacterial properties based on the structure activity relationship while pointing out to their mode of action. It also provides an insight into a variety of approaches resulting in elegant manipulations of their basic skeleton and some breakthroughs in their synthetic strategies of a few widely used drugs, which had helped in accelerating their market growth as well as continuing research for newer fluoroquinolones. Since the mode of action of fluoroquinolones being different from beta-lactams and their transportation to the target site is slow several dual action quinolonyl-beta-lactams (Penicillins, Cephalosporins, Penems, Cephems, Carbapenams etc.) have come as a major breakthrough among the hybrid antibiotics. While focusing on the multifunctional activities of such compounds, this review briefly points out to the current trends in various techniques for de novo drug design and development of newer therapeutic molecules, which hold future promises in combating the fight against drug resistant bacteria as it still remains to be won.

  4. Gemifloxacin: a new fluoroquinolone approved for treatment of respiratory infections.

    PubMed

    Yoo, Bong K; Triller, Darren M; Yong, Chul-Soon; Lodise, Thomas P

    2004-01-01

    To evaluate the microbiology, pharmacokinetic parameters, drug interactions, and results of the available clinical trials of gemifloxacin for the treatment of community-acquired pneumonia (CAP) and acute exacerbation of chronic bronchitis (AECB). MEDLINE (1966-September 2003) was searched for primary and review articles. Data from the manufacturer were also included. Key words included adverse effects, clinical trials, drug interactions, gemifloxacin, and pharmacokinetic parameters. All articles and product labeling concerning gemifloxacin, a fluoroquinolone antibiotic recently approved by the Food and Drug Administration for treatment of CAP and AECB, were included for review. Compared with currently available fluoroquinolones, gemifloxacin demonstrated improved in vitro activity against Streptococcus pneumoniae (minimum inhibitory concentration for 90% eradication 0.03 microg/mL) and similar activity against gram-negative respiratory pathogens (Haemophilus influenzae, Moraxella catarrhalis) and atypical pathogens such as Chlamydia pneumoniae, Legionella pneumophila, and Mycoplasma pneumoniae. Gemifloxacin, consistent with other available fluoroquinolones, has insufficient activity against methicillin-resistant Staphylococcus aureus to allow clinical use for such infections. Gemifloxacin has adequate bioavailability and a favorable drug interaction profile. Gemifloxacin was comparable to commonly employed nonfluoroquinolone regimens for treatment of CAP and AECB, although the studies were designed to demonstrate equivalence. Gemifloxacin once daily for 5-7 days was well tolerated in controlled and uncontrolled clinical studies. Available clinical data, however, are insufficient to draw clinical or toxicologic distinctions between gemifloxacin and other fluoroquinolones. Gemifloxacin may be a suitable choice for empiric treatment of CAP or AECB. However, due to the significant history of fluoroquinolone-induced hepatic failure and dermatologic complications, the

  5. Binding characteristics of fluoroquinolones to synthetic levodopa melanin.

    PubMed

    Ono, Chiho; Tanaka, Makoto

    2003-08-01

    To define the binding characteristics of fluoroquinolones to synthetic levodopa melanin, the binding of various drugs, including levofloxacin and ofloxacin, and positive controls (timolol and chloroquine), was investigated in-vitro. The affinity and capacity of the drug binding were calculated by Langmuir's adsorption isotherm. The affinity constant (K) and the binding capacity (r(max)) of levofloxacin were similar to those of timolol and much lower than those of chloroquine. Racemic ofloxacin and its enantiomers showed similar K and r(max), suggesting that the binding lacked stereoselectivity. The binding experiment with levofloxacin derivatives indicated that the basic nitrogen atom at position 7 of the quinolone ring, but not carboxyl group at position 3, would play a critical role in the interaction of fluoroquinolones with melanin. The melanin-drug complexes of levofloxacin and chloroquine were washed with neutral phosphate buffer, ethanol and 1 M HCl solution to explain the nature of the interaction of melanin with the drugs. Electrostatic forces mainly participate in the formation of the chloroquine-melanin complex, whereas van der Waals' and hydrophobic interactions are involved in the levofloxacin-melanin complex in addition to electrostatic forces. The interactions of various fluoroquinolones such as norfloxacin, enoxacin, sparfloxacin, ciprofloxacin and lomefloxacin with melanin were also studied. The results showed that the relative K value was: chloroquine approximately ciprofloxacin, sparfloxacin >/= lomefloxacin > timolol, levofloxacin approximately enoxacin, norfloxacin, and that the relative r(max) value was: norfloxacin, enoxacin >/= chloroquine, sparfloxacin > levofloxacin, ciprofloxacin, timolol, lomefloxacin. The fluoroquinolones vary in their affinity and capacity to bind with melanin, and ciprofloxacin and sparfloxacin showed a stronger interaction with melanin than the other fluoroquinolones studied.

  6. [The use of fluoroquinolones in bacterial urinary tract infections in cats].

    PubMed

    Kramer, S; Kietzmann, M; Pankow, W-R

    2012-04-24

    Older cats (>10 years) with FLUTD (Feline Lower Urinary Tract Disease) symptoms are often affected by urinary tract infections. In most of these cats organ diseases (e.g. chronic renal failure, diabetes mellitus) or iatrogenic factors (immunosuppressive drugs, indwelling catheter) are found that clearly predispose cats to this kind of infection. From a diagnostic point of view, urinalysis and urine culture are the most important tools in detecting bacteriuria. The microbiological spectrum is thereby comparable to that found in dogs, revealing Escherichia ( E. ) coli but also Staphylococcus spp. and Enterococcus spp./ Streptococcus spp. Antibiotic therapy should be based on the results of susceptibility testing. If this kind of information is not available, drug selection has to be decided on an empirical basis unless it is a complicated urinary tract infection. Preferred antibiotics should have a high renal excretion rate and thus ensure therapeutically effective drug levels in the urine. In this respect, the fluoroquinolones belong to the group of appropriate drugs to be used in cats. The relevance of therapeutical drug concentrations achievable in the urine is discussed for the example of marbofloxacin, a third-generation fluoroquinolone. New pharmacokinetic data showed that marbofloxacin concentrations of ≥2µg/ml are maintained in the urine of healthy cats for 72 and 103 hours after administration of 2 and 4mg/kg BW s.c., respectively.

  7. Fluoroquinolones inhibit preferentially Streptococcus pneumoniae DNA topoisomerase IV than DNA gyrase native proteins.

    PubMed

    Fernandez-Moreira, E; Balas, D; Gonzalez, I; de la Campa, A G

    2000-01-01

    The genes encoding the subunits of DNA topoisomerase IV (parC and parE) and DNA gyrase (gyrA and gyrB) of Streptococcus pneumoniae were cloned and overproduced in Escherichia coli by using the T7promoter-T7 RNA polymerase system. The four subunits were separately purified to near homogeneity by column chromatography. Protein purification was achieved by DEAE-sepharose, heparin-agarose, and hydroxylapatite chromatography. DNA topoisomerase IV was reconstituted when ParC and ParE were combined at a 3.8-fold excess of ParE. The reconstituted topoisomerase IV showed to generate efficient ATP-dependent DNA decatenation activity. The DNA gyrase ATP-dependent supercoiling activity was reconstituted by mixing equimolar amounts of the two gyrase subunits. The inhibitory effects of four representative fluoroquinolones on the DNA decatenation activity of topoisomerase IV and DNA supercoiling of gyrase have been examined and compared. All four compounds were more active in inhibiting topoisomerase IV than gyrase. Moreover, there was a positive correlation between the inhibitory activity against topoisomerase IV decatenation and DNA gyrase supercoiling. The classification of the four fluoroquinolones, considering their inhibitory activities in decatenation, supercoiling and growth was the following: clinafloxacin > trovafloxacin > sparfloxacin > ciprofloxacin. These results suggest these drugs primarily target topoisomerase IV of S. pneumoniae, and gyrase secondarily, in agreement with genetic data.

  8. 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

  9. Implementing an intensified antibiotic stewardship programme targeting cephalosporin and fluoroquinolone use in a 200-bed community hospital in Germany.

    PubMed

    Borde, J P; Litterst, S; Ruhnke, M; Feik, R; Hübner, J; deWith, K; Kaier, K; Kern, W V

    2015-02-01

    Prescription of third-generation cephalosporins and fluoroquinolones has been linked to an increasing incidence of gram-negative bacteria producing extended-spectrum beta-lactamases, methicillin-resistant Staphylococcus aureus and nosocomial infection with Clostridium difficile. Antibiotic stewardship (ABS) programmes offer evidence-based tools to control antibiotic prescription rates and thereby influence the incidence of nosocomial infection and contain the development of multidrug-resistant bacteria, but there is limited experience with such programmes at community hospitals. We implemented an ABS programme at a 200-bed community hospital and aimed at a > 30 % reduction of cephalosporin and fluoroquinolone consumption within 1 year. Pharmacy data were obtained to estimate hospital-wide drug use density expressed in WHO-ATC-defined daily doses (DDD) or hospital-adapted recommended daily doses (RDD) per 1,000 patient days. The effect of the ABS intervention on drug use density was analysed using interrupted time-series analysis for the periods between January 2011 and March 2013 as pre-intervention, and between April 2013 and March 2014 as post-intervention period. The CDI incidence was calculated based on microbiology laboratory data. Cephalosporin use (measured in RDD/1,000 patient days) decreased by 33 %, and fluoroquinolone use decreased by 31 %, respectively. Interrupted time-series analysis confirmed significant changes in the drug use density trends for both cephalosporins and fluoroquinolones after the intervention as well as for total antibiotic use that decreased by 11 % while no significant effect was noted for CDI incidence rates. ABS programmes can be effective in community hospitals and may help establish ecologically advantageous antibiotic strategies when needed.

  10. 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.

  11. Fluoroquinolone resistance in atypical pneumococci and oral streptococci: evidence of horizontal gene transfer of fluoroquinolone resistance determinants from Streptococcus pneumoniae.

    PubMed

    Ip, Margaret; Chau, Shirley S L; Chi, Fang; Tang, Julian; Chan, Paul K

    2007-08-01

    Atypical strains, presumed to be pneumococcus, with ciprofloxacin MICs of > or =4.0 microg/ml and unique sequence variations within the quinolone resistance-determining regions (QRDRs) of the gyrase and topoisomerase genes in comparison with the Streptococcus pneumoniae R6 strain, were examined. These strains were reidentified using phenotypic methods, including detection of optochin susceptibility, bile solubility, and agglutination by serotype-specific antisera, and genotypic methods, including detection of pneumolysin and autolysin genes by PCR, 16S rRNA sequencing, and multilocus sequence typing (MLST). The analysis based on concatenated sequences of the six MLST loci distinguished the "atypical" strains from pneumococci, and these strains clustered closely with S. mitis. However, all these strains and five of nine strains from the viridans streptococcal group possessed one to three gyrA, gyrB, parC, and parE genes whose QRDR sequences clustered with those of S. pneumoniae, providing evidence of horizontal transfer of the QRDRs of the gyrase and topoisomerase genes from pneumococci into viridans streptococci. These genes also conferred fluoroquinolone resistance to viridans streptococci. In addition, the fluoroquinolone resistance determinants of 32 well-characterized Streptococcus mitis and Streptococcus oralis strains from bacteremic patients were also compared. These strains have unique amino acid substitutions in GyrA and ParC that were distinguishable from those in fluoroquinolone-resistant pneumococci and the "atypical" isolates. Both recombinational events and de novo mutations play an important role in the development of fluoroquinolone resistance.

  12. SerpinB1 regulates homeostatic expansion of IL-17+ γδ and CD4+ Th17 cells

    PubMed Central

    Zhao, Picheng; Hou, Lifei; Farley, Kalamo; Sundrud, Mark S.; Remold-O'Donnell, Eileen

    2014-01-01

    SerpinB1 is an endogenous inhibitor of serine proteases recognized for its anti-inflammatory and host-protective properties. Although loss of serpinB1 in mice does not result in gross immune deregulation, serpinb1a−/− mice display increased mortality and inflammation-associated morbidity upon challenge with influenza virus. Here, we show that IL-17A+ γδ and CD4+ Th17 cells are already expanded in the lungs of serpinb1a−/− mice at steady-state. Both γδ and αβ+ CD4+ CCR6+ T cells isolated from the lungs of naive serpinb1a−/− mice displayed a skewed transcriptional profile relative to WT cells, including increased Th17 signature transcripts [Il17a, l17f, and Rorc (RORγt)] and decreased Th1 signature transcripts [Ifng, Cxcr3, and Tbx21 (T-bet)] in γδ T cells. In addition to the lung, IL-17A+ γδ and CD4+ Th17 cells were increased in the spleen of naive serpinb1a−/− mice, despite normal αβ and γδ T cell development in the thymus. Within the γδ T cell compartment, loss of serpinb1a prompted selective expansion of Vγ4+ and Vγ6/Vδ1+ cells, which also displayed elevated expression of the proliferating cell nuclear antigen, Ki-67, and IL-17A. Given that serpinb1a is preferentially expressed in WT IL-17A+ γδ and CD4+ Th17 cell subsets vis-à-vis other T cell lineages, our findings reveal a novel function of serpinB1 in limiting untoward expansion of lymphocytes with a Th17 phenotype. PMID:24249741

  13. SerpinB1 regulates homeostatic expansion of IL-17+ γδ and CD4+ Th17 cells.

    PubMed

    Zhao, Picheng; Hou, Lifei; Farley, Kalamo; Sundrud, Mark S; Remold-O'Donnell, Eileen

    2014-03-01

    SerpinB1 is an endogenous inhibitor of serine proteases recognized for its anti-inflammatory and host-protective properties. Although loss of serpinB1 in mice does not result in gross immune deregulation, serpinb1a(-/-) mice display increased mortality and inflammation-associated morbidity upon challenge with influenza virus. Here, we show that IL-17A(+) γδ and CD4(+) Th17 cells are already expanded in the lungs of serpinb1a(-/-) mice at steady-state. Both γδ and αβ(+) CD4(+) CCR6(+) T cells isolated from the lungs of naive serpinb1a(-/-) mice displayed a skewed transcriptional profile relative to WT cells, including increased Th17 signature transcripts [Il17a, l17f, and Rorc (RORγt)] and decreased Th1 signature transcripts [Ifng, Cxcr3, and Tbx21 (T-bet)] in γδ T cells. In addition to the lung, IL-17A(+) γδ and CD4(+) Th17 cells were increased in the spleen of naive serpinb1a(-/-) mice, despite normal αβ and γδ T cell development in the thymus. Within the γδ T cell compartment, loss of serpinb1a prompted selective expansion of Vγ4(+) and Vγ6/Vδ1(+) cells, which also displayed elevated expression of the proliferating cell nuclear antigen, Ki-67, and IL-17A. Given that serpinb1a is preferentially expressed in WT IL-17A(+) γδ and CD4(+) Th17 cell subsets vis-à-vis other T cell lineages, our findings reveal a novel function of serpinB1 in limiting untoward expansion of lymphocytes with a Th17 phenotype.

  14. An ecological study of food desert prevalence and 4th grade academic achievement in new york state school districts.

    PubMed

    Frndak, Seth E

    2014-12-02

    This ecological study examines the relationship between food desert prevalence and academic achievement at the school district level. Sample included 232 suburban and urban school districts in New York State. Multiple open-source databases were merged to obtain: 4(th) 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. 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. 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 healthThe 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 the school district level. Significant variation in

  15. Synapses as therapeutic targets for autism spectrum disorders: an international symposium held in pavia on july 4th, 2014.

    PubMed

    Curatolo, Paolo; Ben-Ari, Yehezkel; Bozzi, Yuri; Catania, Maria Vincenza; D'Angelo, Egidio; Mapelli, Lisa; Oberman, Lindsay M; Rosenmund, Christian; Cherubini, Enrico

    2014-01-01

    New progresses into the molecular and cellular mechanisms of autism spectrum disorders (ASDs) have been discussed in 1 day international symposium held in Pavia (Italy) on July 4th, 2014 entitled "synapses as therapeutic targets for autism spectrum disorders" (satellite of the FENS Forum for Neuroscience, Milan, 2014). In particular, world experts in the field have highlighted how animal models of ASDs have greatly advanced our understanding of the molecular pathways involved in synaptic dysfunction leading sometimes to "synaptic clinical trials" in children.

  16. 4th Global CRO Council for Bioanalysis: coadministered drugs stability, EMA/US FDA guidelines, 483s and carryover.

    PubMed

    Lowes, Steve; Jersey, Jim; Shoup, Ronald; Garofolo, Fabio; Needham, Shane; Couerbe, Philippe; Lansing, Tim; Bhatti, Masood; Sheldon, Curtis; Hayes, Roger; Islam, Rafiq; Lin, Zhongping; Garofolo, Wei; Moussallie, Marc; Teixeira, Leonardo de Souza; Rocha, Thais; Jardieu, Paula; Truog, James; Lin, Jenny; Lundberg, Richard; Breau, Alan; Dilger, Carmen; Bouhajib, Mohammed; Levesque, Ann; Gagnon-Carignan, Sofi; Jenkins, Rand; Nicholson, Robert; Lin, Ming Hung; Karnik, Shane; DeMaio, William; Smith, Kirk; Cojocaru, Laura; Allen, Mike; Fatmi, Saadya; Sayyarpour, Farhad; Malone, Michele; Fang, Xinping

    2012-04-01

    The Global CRO Council for Bioanalysis (GCC) was formed in September 2010. Since then, the representatives of the member companies come together periodically to openly discuss bioanalysis and the regulatory challenges unique to the outsourcing industry. The 4th GCC Closed Forum brought together experts from bioanalytical CROs to share and discuss recent issues in regulated bioanalysis, such as the impact of coadministered drugs on stability, some differences between European Medicines Agency and US FDA bioanalytical guidance documents and lessons learned following recent Untitled Letters. Recent 483s and agency findings, as well as issues on method carryover, were also part of the topics discussed.

  17. 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.

  18. On information process in living matter. Time and the 4th dimension. (exposé of a hypothesis).

    PubMed

    Arianova, L W

    1981-04-01

    The hypothesis concerns the nature of the biological information signal. It is envisaged as a unit existing in two different states -- dipole and monopole according to its location in the three-dimensional space, respectively in the 4th dimension. The reversible transformation dipole-monopole which marks the crucial phase of the information process in living organisms outlines a two-way functioning tunnel in the space. According to the hypothesis this two-way tunnel in the space fixes the fundamental difference between living and non-living matter.

  19. Synapses as Therapeutic Targets for Autism Spectrum Disorders: An International Symposium Held in Pavia on July 4th, 2014

    PubMed Central

    Curatolo, Paolo; Ben-Ari, Yehezkel; Bozzi, Yuri; Catania, Maria Vincenza; D’Angelo, Egidio; Mapelli, Lisa; Oberman, Lindsay M.; Rosenmund, Christian; Cherubini, Enrico

    2014-01-01

    New progresses into the molecular and cellular mechanisms of autism spectrum disorders (ASDs) have been discussed in 1 day international symposium held in Pavia (Italy) on July 4th, 2014 entitled “synapses as therapeutic targets for autism spectrum disorders” (satellite of the FENS Forum for Neuroscience, Milan, 2014). In particular, world experts in the field have highlighted how animal models of ASDs have greatly advanced our understanding of the molecular pathways involved in synaptic dysfunction leading sometimes to “synaptic clinical trials” in children. PMID:25324723

  20. Report on the 4'th scientific meeting of the "Verein zur Förderung des Wissenschaftlichen Nachwuchses in der Neurologie" (NEUROWIND e.V.) held in Motzen, Germany, Nov. 2'nd - Nov. 4'th, 2012.

    PubMed

    Linker, Ralf A; Meuth, Sven G; Magnus, Tim; Korn, Thomas; Kleinschnitz, Christoph

    2012-11-22

    From November 2nd - 4th 2012, the 4th NEUROWIND e.V. meeting was held in Motzen, Brandenburg, Germany. Again more than 60 participants, predominantly at the doctoral student or postdoc level, gathered to share their latest findings in the fields of neurovascular research, neurodegeneration and neuroinflammation. Like in the previous years, the symposium provided an excellent platform for scientific exchange and the presentation of innovative projects in the stimulating surroundings of the Brandenburg outback. This year's keynote lecture on the pathophysiological relevance of neuronal networks was given by Christian Gerloff, Head of the Department of Neurology at the University Clinic of Hamburg-Eppendorf. Another highlight of the meeting was the awarding of the NEUROWIND e.V. prize for young scientists working in the field of experimental neurology. The award is donated by the Merck Serono GmbH, Darmstadt, Germany and is endowed with 20.000 Euro. This year the jury decided unanimously to adjudge the award to Michael Gliem from the Department of Neurology at the University Clinic of Düsseldorf (group of Sebastian Jander), Germany, for his outstanding work on different macrophage subsets in the pathogenesis of ischemic stroke published in the Annals of Neurology in 2012.

  1. Crystal structure and stability of gyrase-fluoroquinolone cleaved complexes from Mycobacterium tuberculosis.

    PubMed

    Blower, Tim R; Williamson, Benjamin H; Kerns, Robert J; Berger, James M

    2016-02-16

    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.

  2. Evaluation of Fluoroquinolones for the Prevention of BK Viremia after Renal Transplantation

    PubMed Central

    Waikar, Sushrut S.; Martin, Spencer; Roberts, Keri; Chen, Jie; Borgi, Lea; Sheashaa, Hussein; Dyer, Christine; Malek, Sayeed K.; Tullius, Stefan G.; Vadivel, Nidyanandh; Grafals, Monica; Abdi, Reza; Najafian, Nader; Milford, Edgar; Chandraker, Anil

    2010-01-01

    Background and objectives: Nearly 30% of renal transplant recipients develops BK viremia, a prerequisite for BK nephropathy. Case reports have evaluated treatment options for BK virus, but no controlled studies have assessed prophylactic therapies. Fluoroquinolone antibiotics were studied for prevention of BK viremia after renal transplantation. Design, setting, participants, & measurements: This retrospective analysis evaluated adult renal transplant recipients with at least one BK viral load (blood) between 90 and 400 days after transplantation. Six to 12 months of co-trimoxazole was used for Pneumocystis prophylaxis. In sulfa-allergic/-intolerant patients, 6 to 12 months of atovaquone with 1 month of a fluoroquinolone was used. Fluoroquinolones can inhibit BK DNA topoisomerase. The two groups studied were those that received 30 days of levofloxacin or ciprofloxacin after transplantation and those that did not. The primary endpoint was BK viremia rates at 1 year. Of note, of the 160 patients not receiving fluoroquinolone prophylaxis, 40 received a fluoroquinolone for treatment of a bacterial infection within 3 months after transplantation. Subgroup analysis evaluating these 40 patients against the 120 who had no exposure to fluoroquinolones was completed. Results: A 1-month fluoroquinolone course after transplantation was associated with significantly lower rates of BK viremia at 1 year compared with those with no fluoroquinolone. In the subgroup analysis, exposure to fluoroquinolone for treatment of bacterial infections within 3 months after transplantation was associated with significantly lower 1-year rates of BK viremia. Conclusions: This analysis demonstrates that fluoroquinolones are effective at preventing BK viremia after renal transplantation. PMID:20507960

  3. 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

  4. In vitro activity of WQ-3810, a novel fluoroquinolone, against multidrug-resistant and fluoroquinolone-resistant pathogens.

    PubMed

    Kazamori, Daichi; Aoi, Hiroshi; Sugimoto, Kaori; Ueshima, Taichi; Amano, Hirotaka; Itoh, Kenji; Kuramoto, Yasuhiro; Yazaki, Akira

    2014-11-01

    The aim of this study was to examine the in vitro antibacterial activity of WQ-3810, a new fluoroquinolone, against clinically relevant pathogens such as Acinetobacter baumannii, Escherichia coli and Streptococcus pneumoniae, including multidrug-resistant (MDR) and fluoroquinolone-resistant (FQR) isolates, compared with those of ciprofloxacin, levofloxacin, moxifloxacin and gemifloxacin. WQ-3810 demonstrated the most potent activity against the antimicrobial-resistant pathogens tested. Against A. baumannii, including MDR isolates, the potency of WQ-3810 [minimum inhibitory concentration for 90% of the organisms (MIC(90))=1 mg/L] was more than eight-fold higher than that of ciprofloxacin (64 mg/L) and levofloxacin (8 mg/L). Against E. coli and S. pneumoniae, including FQR isolates, WQ-3810 (MIC(90)=4 mg/L and 0.06 mg/L, respectively) was also more active than ciprofloxacin (64 mg/L and 2 mg/L) and levofloxacin (32 mg/L and 2 mg/L). Furthermore, WQ-3810 was the most potent among the fluoroquinolones tested against meticillin-resistant Staphylococcus aureus (MRSA) and Neisseria gonorrhoeae, including FQR isolates. In particular, WQ-3810 demonstrated highly potent activity against FQR isolates of A. baumannii, E. coli and S. pneumoniae with amino acid mutation(s) in the quinolone resistance-determining region of DNA gyrase and/or topoisomerase IV, which are the target enzymes of fluoroquinolones. An enzyme inhibition study performed using FQR E. coli DNA gyrase suggested that the potent antibacterial activity of WQ-3810 against drug-resistant isolates partly results from the strong inhibition of the target enzymes. In conclusion, this study demonstrated that WQ-3810 exhibits extremely potent antibacterial activity over the existing fluoroquinolones, particularly against MDR and FQR pathogens. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  5. 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. Copyright © 2015 International Agency for Research on Cancer. Published by Elsevier Ltd. All rights reserved.

  6. Virtual 3-dimensional preoperative planning with the dextroscope for excision of a 4th ventricular ependymoma.

    PubMed

    Anil, S M; Kato, Y; Hayakawa, M; Yoshida, K; Nagahisha, S; Kanno, T

    2007-04-01

    Advances in computer imaging and technology have facilitated enhancement in surgical planning with a 3-dimensional model of the surgical plan of action utilizing advanced visualization tools in order to plan individual interactive operations with the aid of the dextroscope. This provides a proper 3-dimensional imaging insight to the pathological anatomy and sets a new dimension in collaboration for training and education. The case of a seventeen-year-old female, being operated with the aid of a preoperative 3-dimensional virtual reality planning and the practical application of the neurosurgical operation, is presented. This young lady presented with a two-year history of recurrent episodes of severe, global, throbbing headache with episodes of projectile vomiting associated with shoulder pain which progressively worsened. She had no obvious neurological deficits on clinical examination. CT and MRI showed a contrast-enhancing midline posterior fossa space-occupying lesion. Utilizing virtual imaging technology with the aid of a dextroscope which generates stereoscopic images, a 3-dimensional image was produced with the CT and MRI images. A preoperative planning for excision of the lesion was made and a real-time 3-dimensional volume was produced and surgical planning with the dextroscope was made and the lesion excised. Virtual reality has brought new proportions in 3-dimensional planning and management of various complex neuroanatomical problems that are faced during various operations. Integration of 3-dimensional imaging with stereoscopic vision makes understanding the complex anatomy easier and helps improve decision making in patient management.

  7. The fluoroquinolone antibacterials: past, present and future perspectives.

    PubMed

    Appelbaum, P C; Hunter, P A

    2000-09-01

    The history of the development of the quinolones is described from the first quinolone, nalidixic acid, via the first 6-fluorinated quinolone norfloxacin, to the latest extended-spectrum fluoroquinolones. The structural modifications made to the basic quinolone and naphthyridone nucleus and to the side chains have allowed improvements to be made such that the next group of fluoroquinolones after norfloxacin, exemplified by ciprofloxacin, had high activity against gram-negative species and a number of atypical pathogens, good-to-moderate activity against gram-positive species and were well absorbed and distributed. These compounds have been successfully used in the clinic for a decade and the size of the market has risen in recent years to only a little less than that for penicillins and macrolides. Notwithstanding the broad spectrum of these compounds, defects became evident. The growth in understanding of structure activity relationships with fluoroquinolones has enabled the development of even better compounds. The targets in fluoroquinolone research during the last few years include: improvements in pharmacokinetic properties, greater activity against gram-positive cocci and anaerobes, activity against fluoroquinolone-resistant strains, and improvements in activity against non-fermentative gram-negative species. The compounds developed in the recent years have fulfilled some but not all of these goals; improved bioavailability is one target achieved with most of the more recent compounds allowing for once-daily dosing. Gatifloxacin, moxifoxacin and trovafloxacin have all greatly improved the activity against gram-positive cocci, particularly pneumococci, and against anaerobes. They are not quite as active as ciprofloxacin against Enterobacteriaceae, and show no substantial improvements in activity against non-fermentative species. Clinafloxacin, gemifloxacin and sitafloxacin have even better activity against gram-positive cocci and are as active as ciprofloxacin

  8. Efficient Reduction of Antibacterial Activity and Cytotoxicity of Fluoroquinolones by Fungal-Mediated N-Oxidation.

    PubMed

    Rusch, Marina; Spielmeyer, Astrid; Meißner, Jessica; Kietzmann, Manfred; Zorn, Holger; Hamscher, Gerd

    2017-04-19

    Extensive usage of fluoroquinolone antibiotics in livestock results in their occurrence in manure and subsequently in the environment. Fluoroquinolone residues may promote bacterial resistance and are toxic to plants and aquatic organisms. Moreover, fluoroquinolones may enter the food chain through plant uptake, if manure is applied as fertilizer. Thus, the presence of fluoroquinolones in the environment may pose a threat to human and ecological health. In this study, the biotransformation of enrofloxacin, marbofloxacin, and difloxacin by the fungus X. longipes (Xylaria) was investigated. The main metabolites were unequivocally identified as the respective N-oxides by mass spectrometry and nuclear magnetic resonance spectroscopy. Fungal-mediated N-oxidation of fluoroquinolones led to a 77-90% reduction of the initial antibacterial activity. In contrast to their respective parent compounds, N-oxides showed low cytotoxic potential and had a reduced impact on cell proliferation. Thus, biotransformation by X. longipes may represent an effective method for inactivating fluoroquinolones.

  9. Influence of renal function on the pharmacokinetics of lomefloxacin compared with other fluoroquinolones.

    PubMed

    Blum, R A

    1992-04-06

    Fluoroquinolones have similar chemical structures but wide differences in their pharmacokinetic profiles. Disparity in fluoroquinolone elimination is most evident in patients with various degrees of renal insufficiency. Ofloxacin is almost exclusively eliminated by the kidney, whereas pefloxacin is predominantly cleared by the liver. The fluoroquinolones eliminated by both renal and nonrenal routes (hepatic and transintestinal) include norfloxacin, ciprofloxacin, enoxacin, fleroxacin, temafloxacin, and lomefloxacin. The primary renal mechanism of elimination for norfloxacin, ciprofloxacin, enoxacin, fleroxacin, temafloxacin, and lomefloxacin is glomerular filtration and tubular secretion. Both total clearance and renal clearance significantly correlate with creatinine clearance for these fluoroquinolones, and creatinine clearance is a useful clinical marker on which to base dosage adjustments. For some fluoroquinolones, dosage adjustments are recommended when creatinine clearances fall below 30-40 mL/min. This is especially evident for lomefloxacin, temafloxacin, norfloxacin, ciprofloxacin, enoxacin, and fleroxacin. There is very little removal of fluoroquinolones from the plasma during hemodialysis due to their extensive tissue distribution.

  10. 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

  11. 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.

  12. Comparative Killing Rates of Fluoroquinolones and Cell Wall-Active Agents

    PubMed Central

    Fung-Tomc, Joan C.; Gradelski, Elizabeth; Valera, Lourdes; Kolek, Benjamin; Bonner, Daniel P.

    2000-01-01

    Killing rates of fluoroquinolones, β-lactams, and vancomycin were compared against Enterobacteriaceae, Staphylococcus aureus, pneumococci, streptococci, and Enterococcus faecalis. The times required for fluoroquinolones to decrease viability by 3 log10 were 1.5 h for Enterobacteriaceae, 4 to 6 h for staphylococci, and ≥6 h for streptococci and enterococci. Thus, the rate of killing by fluoroquinolones is organism group dependent; overall, they killed more rapidly than β-lactams and vancomycin. PMID:10770784

  13. Relationships among Ciprofloxacin, Gatifloxacin, Levofloxacin, and Norfloxacin MICs for Fluoroquinolone-Resistant Escherichia coli Clinical Isolates▿

    PubMed Central

    Becnel Boyd, Lauren; Maynard, Merry J.; Morgan-Linnell, Sonia K.; Horton, Lori Banks; Sucgang, Richard; Hamill, Richard J.; Jimenez, Javier Rojo; Versalovic, James; Steffen, David; Zechiedrich, Lynn

    2009-01-01

    Fluoroquinolones are some of the most prescribed antibiotics in the United States. Previously, we and others showed that the fluoroquinolones exhibit a class effect with regard to the CLSI-established breakpoints for resistance, such that decreased susceptibility (i.e., an increased MIC) to one fluoroquinolone means a simultaneously decreased susceptibility to all. For defined strains, however, clear differences exist in the pharmacodynamic properties of each fluoroquinolone and the extent to which resistance-associated genotypes affect the MICs of each fluoroquinolone. In a pilot study of 920 clinical Escherichia coli isolates, we uncovered tremendous variation in norfloxacin MICs. The MICs for all of the fluoroquinolone-resistant isolates exceeded the resistance breakpoint, reaching 1,000 μg/ml. Approximately 25% of the isolates (n = 214), representing the full range of resistant norfloxacin MICs, were selected for the simultaneous determinations of ciprofloxacin, gatifloxacin, levofloxacin, and norfloxacin MICs. We found that (i) great MIC variation existed for all four fluoroquinolones, (ii) the ciprofloxacin and levofloxacin MICs of >90% of the fluoroquinolone-resistant isolates were higher than the resistance breakpoints, (iii) ciprofloxacin and levofloxacin MICs were distributed into two distinct groups, (iv) the MICs of two drug pairs (ciprofloxacin and norfloxacin by Kendall's Tau-b test and gatifloxacin and levofloxacin by paired t test) were similar with statistical significance but were different from each other, and (v) ∼2% of isolates had unprecedented fluoroquinolone MIC relationships. Thus, although the fluoroquinolones can be considered equivalent with regard to clinical susceptibility or resistance, fluoroquinolone MICs differ dramatically for fluoroquinolone-resistant clinical isolates, likely because of differences in drug structure. PMID:18838594

  14. Fluoroquinolone Sequential Therapy for Helicobacter pylori: A Meta-analysis.

    PubMed

    Kale-Pradhan, Pramodini B; Mihaescu, Anela; Wilhelm, Sheila M

    2015-08-01

    As resistance of Helicobacter pylori to standard first-line therapy is increasing globally, alternative treatment regimens, such as a fluoroquinolone-based sequential regimen, have been explored. The objective of this meta-analysis was to compare the efficacy of fluoroquinolone-based sequential therapy with standard first-line treatment for H. pylori infection. Meta-analysis of six randomized controlled trials. A total of 738 H. pylori-infected, treatment-naive adults who received fluoroquinolone-based sequential therapy (5-7 days of a proton pump inhibitor [PPI] and amoxicillin therapy followed by 5-7 days of a PPI, a fluoroquinolone, and metronidazole or tinidazole or furazolidone therapy) and 733 H. pylori-infected, treatment-naive adults who received guideline-recommended, first-line therapy with standard triple therapy (7-14 days of a PPI plus amoxicillin and clarithromycin) or standard sequential therapy (5 days of a PPI plus amoxicillin, followed by an additional 5 days of triple therapy consisting of a PPI, clarithromycin, and metronidazole or tinidazole). A systematic literature search of the MEDLINE, PubMed, and Cochrane Central Register of Controlled Trials databases (from inception through January 2015) was conducted to identify randomized controlled trials that compared fluoroquinolone-based sequential therapy with guideline-recommended, first-line treatment regimens in H. pylori-infected, treatment-naive adults. All selected trials confirmed H. pylori infection prior to treatment as well as post-treatment eradication. A meta-analysis was performed by using Review Manager 5.2. Treatment effect was determined with a random-effects model by using the Mantel-Haenszel method and was reported as a risk ratio (RR) with 95% confidence interval (CI). In the six randomized controlled trials that met the inclusion criteria, 648 (87.8%) of 738 patients receiving fluoroquinolone-based sequential therapy and 521 (71.1%) of 733 patients receiving standard

  15. Fluoroquinolones: an important class of antibiotics against tuberculosis.

    PubMed

    De Souza, Marcus Vinícius Nora; Vasconcelos, Thatyana Rocha Alves; de Almeida, Mauro Vieira; Cardoso, Sílvia Helena

    2006-01-01

    Tuberculosis (TB) is a global health problem due to the lack of new drugs in the market and also due to the advent of multidrug resistant strains (MDR). This disease affects around 8 million people and kills almost 3 million people each year and it is estimated that there are 1 billion infected with TB worldwide. Due to this problem fluoroquinolones have attracted much attention as the new class of anti TB drugs due to their fewer toxic side effects, improved pharmacokinetic properties and extensive and potent activity against Gram-positive and Gram-negative bacteria, including resistant strains. In this present review we report fluoroquinolones as a promising new class of anti TB.

  16. Newer fluoroquinolones in the treatment of acute exacerbations of COPD.

    PubMed

    Patel, Amit; Wilson, Robert

    2006-01-01

    Acute exacerbations of COPD are a major cause of morbidity and mortality. Bacteria are implicated in about half of all cases. The frequency of exacerbations is related to decline in lung function and poorer quality of life. 25% of patients with COPD have bacterial colonization of the lower airways in stable state whereas non-smokers without COPD have airways that are sterile. The significance of the colonization is unclear, but there is emerging evidence that it may be detrimental. Much of the data recommending antibiotic treatment are based on findings more than 10 years old and do not take into account emerging bacterial resistance. This article reviews these data and that from newer antibiotic trials. It also reviews current antibiotic prescribing guidelines from major respiratory societies around the world. Recent antibiotic trials have compared fluoroquinolones with "standard" antibiotics and found, in the main, longer exacerbation-free intervals and better bacterial eradication rates in those treated with fluoroquinolones.

  17. Newer fluoroquinolones in the treatment of acute exacerbations of COPD

    PubMed Central

    Patel, Amit; Wilson, Robert

    2006-01-01

    Acute exacerbations of COPD are a major cause of morbidity and mortality. Bacteria are implicated in about half of all cases. The frequency of exacerbations is related to decline in lung function and poorer quality of life. 25% of patients with COPD have bacterial colonization of the lower airways in stable state whereas non-smokers without COPD have airways that are sterile. The significance of the colonization is unclear, but there is emerging evidence that it may be detrimental. Much of the data recommending antibiotic treatment are based on findings more than 10 years old and do not take into account emerging bacterial resistance. This article reviews these data and that from newer antibiotic trials. It also reviews current antibiotic prescribing guidelines from major respiratory societies around the world. Recent antibiotic trials have compared fluoroquinolones with “standard” antibiotics and found, in the main, longer exacerbation-free intervals and better bacterial eradication rates in those treated with fluoroquinolones. PMID:18046861

  18. Maintaining Fluoroquinolone Class Efficacy: Review of Influencing Factors

    PubMed Central

    2003-01-01

    Previous experience with antimicrobial resistance has emphasized the importance of appropriate stewardship of these pharmacotherapeutic agents. The introduction of fluoroquinolones provided potent new drugs directed primarily against gram-negative pathogens, while the newer members of this class demonstrate more activity against gram-positive species, including Streptococcus pneumoniae. Although these agents are clinically effective against a broad range of infectious agents, emergence of resistance and associated clinical failures have prompted reexamination of their use. Appropriate use revolves around two key objectives: 1) only prescribing antimicrobial therapy when it is beneficial and 2) using the agents(s) with optimal activity against the expected pathogens(s). Pharmacodynamic principles and properties can be applied to achieve the latter objective when prescribing agents belonging to the fluoroquinolone class. A focused approach emphasizing “correct-spectrum” coverage may reduce development of antimicrobial resistance and maintain class efficacy. PMID:12533274

  19. Structure-Activity Relationship of Fluoroquinolones Against K. pneumoniae

    NASA Astrophysics Data System (ADS)

    Li, Xiao-hong; Zhang, Rui-zhou; Cheng, Xin-lu; Yang, Xiang-dong

    2007-04-01

    The structure-activity relationship of fluoroquinolones, which show anti-K. pneumoniae activity, was studied by using principal component analysis (PCA) and hierarchical cluster analysis (HCA). The PCA results showed that the lowest unoccupied molecular orbital energy, energy difference between the highest occupied and the lowest unoccupied molecular orbital, dipole moment, net atomic charge on atom I, molecular polarizability, partition coefficient and molecular refractivity of these compounds are responsible for the separation between high-activity and low-activity groups. The HCA results were similar to those obtained with PCA. By using the chemometric results, four synthetic compounds were analyzed through PCA and HCA, and three of them are proposed as active molecules against K. pneumoniae which is consistent with the results of clinical experiments. The methodologies of PCA and HCA provide a reliable rule for classifying new fluoroquinolones with anti-K. pneumoniae activity.

  20. 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

  1. Reforming the 4th-Year Curriculum as a Springboard to Graduate Medical Training: One School's Experiences and Lessons Learned.

    PubMed

    Wackett, Andrew; Daroowalla, Feroza; Lu, Wei-Hsin; Chandran, Latha

    2016-01-01

    Concerns regarding the quality of training in the 4th year of medical school and preparation of graduates to enter residency education persist and are borne out in the literature. We reviewed the published literature regarding Year 4 concerns as well as institutional efforts to improve the 4th-year curriculum from several schools. Based on input from key stakeholders, we established 4 goals for our Year 4 curriculum reform: (a) standardize the curricular structure, (b) allow flexibility and individualization, (c) improve the preparation for residency, and (d) improve student satisfaction. After the reform, we evaluated the outcomes using results from the Association of American Medical Colleges Questionnaire, student focus groups, and program director surveys. This article describes the context, process, and outcomes of the reform of the Year 4 curriculum at Stony Brook University School of Medicine. We were able to achieve all four stated goals for the reform. The significant components of the change included a flexible adaptable curriculum based on individual needs and preferences, standardized learning objectives across the year, standardized competency-based evaluations regardless of discipline, reinforcement of clinical skills, and training for the transition to the workplace as an intern. The reform resulted in increased student satisfaction, increased elective time, and increased preparedness for residency training as perceived by the graduates. The Program Director survey showed significant changes in ability to perform a medical history and exam, management of common medical conditions and emergencies, clinical reasoning and problem-solving skills, working and communication with the healthcare team, and overall professionalism in meeting obligations inherent in the practice of medicine. Lessons learned from our 4th-year reform process are discussed. Listening to the needs of the stakeholders was an important step in ensuring buy-in, having an institutional

  2. Effect of fluoroquinolones on mitochondrial function in pancreatic beta cells.

    PubMed

    Ghaly, Hany; Jörns, Anne; Rustenbeck, Ingo

    2014-02-14

    Hyper- and hypoglycaemias are known side effects of fluoroquinolone antibiotics, resulting in a number of fatalities. Fluoroquinolone-induced hypoglycaemias are due to stimulated insulin release by the inhibition of the KATP channel activity of the beta cell. Recently, it was found that fluoroquinolones were much less effective on metabolically intact beta cells than on open cell preparations. Thus the intracellular effects of gatifloxacin, moxifloxacin and ciprofloxacin were investigated by measuring NAD(P)H- and FAD-autofluorescence, the mitochondrial membrane potential, and the adenine nucleotide content of isolated pancreatic islets and beta cells. 100 μM of moxifloxacin abolished the NAD(P)H increase elicited by 20mM glucose, while gatifloxacin diminished it and ciprofloxacin had no significant effect. This pattern was also seen with islets from SUR1 Ko mice, which have no functional KATP channels. Moxifloxacin also diminished the glucose-induced decrease of FAD-fluorescence, which reflects the intramitochondrial production of reducing equivalents. Moxifloxacin, but not ciprofloxacin or gatifloxacin significantly reduced the effect of 20mM glucose on the ATP/ADP ratio. The mitochondrial hyperpolarization caused by 20mM glucose was partially antagonized by moxifloxacin, but not by ciprofloxacin or gatifloxacin. Ultrastructural analyses after 20 h tissue culture showed that all three compounds (at 10 and 100 μM) diminished the number of insulin secretory granules and that gatifloxacin and ciprofloxacin, but not moxifloxacin induced fission/fusion configurations of the beta cell mitochondria. In conclusion, fluoroquinolones affect the function of the mitochondria in pancreatic beta cells which may diminish the insulinotropic effect of KATP channel closure and contribute to the hyperglycaemic episodes. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Lessons Learned in Antibiotic Stewardship: Fluoroquinolone Use in Pediatrics.

    PubMed

    Hersh, Adam L; Gerber, Jeffrey S; Hicks, Lauri A; Pavia, Andrew T

    2015-03-01

    The use of fluoroquinolones differs dramatically between adult and pediatric patients. For adults, they are the leading class of antibiotics prescribed in ambulatory care visits whereas in children, they are the least frequently prescribed class. The reasons for this difference in practice likely relate to perceptions of their potential for harm. This highlights the impact of physicians' perception of direct patient harm in antibiotic decision making which has implications for antibiotic stewardship.

  4. 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

    2014-05-02

    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.

  5. Dose-related selection of fluoroquinolone-resistant Escherichia coli.

    PubMed

    Olofsson, Sara K; Marcusson, Linda L; Strömbäck, Ann; Hughes, Diarmaid; Cars, Otto

    2007-10-01

    To investigate the effects of clinically used doses of norfloxacin, ciprofloxacin and moxifloxacin on survival and selection in Escherichia coli populations containing fluoroquinolone-resistant subpopulations and to measure the value of the pharmacodynamic index AUC/mutant prevention concentration (MPC) that prevents the growth of pre-existing resistant mutants. Mixed cultures of susceptible wild-type and isogenic single (gyrA S83L) or double (gyrA S83L, Delta marR) fluoroquinolone-resistant mutants were exposed to fluoroquinolones for 24 h in an in vitro kinetic model. Antibiotic concentrations modelled pharmacokinetics attained with clinical doses. All tested doses eradicated the susceptible wild-type strain. Norfloxacin 200 mg administered twice daily selected for both single and double mutants. Ciprofloxacin 250 mg administered twice daily eradicated the single mutant, but not the double mutant. For that, 750 mg administered twice daily was required. Moxifloxacin 400 mg once daily eliminated the single mutant, but did not completely remove the double mutant. The MPC of ciprofloxacin was determined and based on those dose simulations that eradicated mutant subpopulations, an AUC/MPC(wild-type) of 35 prevented selection of the single mutant, whereas an AUC/MPC(single mutant) of 14 (equivalent to an AUC/MPC(wild-type) of 105) prevented selection of the double mutant. All tested clinical dosing regimens were effective in eradicating susceptible bacteria, but ciprofloxacin 750 mg twice daily was the only dose that prevented the selection of single- and double-resistant E. coli mutants. Thus, among approved fluoroquinolone dosing regimens, some are significantly more effective than others in exceeding the mutant selection window and preventing the enrichment of resistant mutants.

  6. Remarkable increase in fluoroquinolone-resistant Mycoplasma genitalium in Japan.

    PubMed

    Kikuchi, Mina; Ito, Shin; Yasuda, Mitsuru; Tsuchiya, Tomohiro; Hatazaki, Kyoko; Takanashi, Masaki; Ezaki, Takayuki; Deguchi, Takashi

    2014-09-01

    We determined the prevalence of macrolide and fluoroquinolone resistance-associated mutations in Mycoplasma genitalium DNA specimens from men with non-gonococcal urethritis (NGU) and analysed their effects on antibiotic treatments of M. genitalium infections. In this retrospective study, we examined antibiotic resistance-associated mutations in the 23S rRNA, gyrA and parC genes of M. genitalium and the association of the mutations with microbiological outcomes of antibiotic treatments in men with M. genitalium-positive NGU. No macrolide resistance-associated mutations in the 23S rRNA gene were observed in 27 M. genitalium DNA specimens in 2011 and in 24 in 2012. However, 5 of 17 in 2013 had 23S rRNA mutations. Three of 15 in 2011, 6 of 19 in 2012 and 8 of 17 in 2013 had fluoroquinolone resistance-associated alterations in ParC. Three in 2013 had both the antibiotic resistance-associated alterations coincidentally. In two men with M. genitalium harbouring 23S rRNA mutations, the mycoplasma persisted after treatment with a regimen of 2 g of extended-release azithromycin (AZM-SR) once daily for 1 day. All nine men with mycoplasma harbouring ParC alterations were microbiologically cured with a regimen of 100 mg of sitafloxacin twice daily for 7 days. Macrolide- or fluoroquinolone-resistant M. genitalium appears to be increasing, and the increase in fluoroquinolone-resistant mycoplasmas is especially remarkable in Japan. Mycoplasmas harbouring 23S rRNA mutations would be resistant to the AZM-SR regimen, but those harbouring ParC alterations would still be susceptible to the sitafloxacin regimen. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. First Characterization of Fluoroquinolone Resistance in Streptococcus suis▿

    PubMed Central

    Escudero, Jose Antonio; San Millan, Alvaro; Catalan, Ana; de la Campa, Adela G.; Rivero, Estefania; Lopez, Gema; Dominguez, Lucas; Moreno, Miguel Angel; Gonzalez-Zorn, Bruno

    2007-01-01

    We have identified and sequenced the genes encoding the quinolone-resistance determining region (QRDR) of ParC and GyrA in fluoroquinolone-susceptible and -resistant Streptococcus suis clinical isolates. Resistance is the consequence of single point mutations in the QRDRs of ParC and GyrA and is not due to clonal spread of resistant strains or horizontal gene transfer with other bacteria. PMID:17116660

  8. Fluoroquinolone utilization among inpatients in a teaching hospital in western Nepal.

    PubMed

    Shankar, P Ravi; Upadhyay, Dinesh K; Mishra, Pranaya; Subish, P; Dubey, Arun K; Saha, Archana C

    2007-02-01

    To obtain information on the prescribing patterns of fluoroquinolones among hospitalized patients, other antibiotics and drugs co-prescribed, calculate fluoroquinolone utilization using defined daily dose (DDD), calculate mean cost of drugs and detail the sensitivity patterns of isolated microorganisms. The study was carried out over a five-month period (1st November 2003 to 31st March 2004) at the Manipal Teaching Hospital, Pokhara, Nepal. Demographic details and duration of hospitalization was noted. The percentage of patients prescribed parenteral antibiotics and fluoroquinolones were recorded. The cost of drugs was determined using the price list supplied by the pharmacy. Fluoroquinolone utilization was measured in DDD/100 bed-days. Fluoroquinolones were prescribed to 263 patients during the study period; 160 females and 103 males. Mean +/- SD number of drugs prescribed and duration of hospitalization were 6.5 +/- 3.3 and 6.2 +/- 5.4 days respectively. Fluoroquinolone utilization was 7.76 DDD/100 bed-days. Ciprofloxacin was the most commonly prescribed drug (6.83 DDD/100 bed-days). Fluoroquinolones were used for prophylaxis in 110 patients (41.8%). Other indications were urinary tract infections and acute gastroenteritis. E.coli, S.aureus and P. aeruginosa were common organisms isolated. The mean cost of drugs was 13.1 U.S. $ and fluoroquinolones contributed to 36.7% of the total drug costs. The use of fluoroquinolones was high compared to that reported previously.

  9. Consumption patterns and in vitro resistance of Streptococcus pneumoniae to fluoroquinolones.

    PubMed

    Simoens, Steven; Verhaegen, Jan; van Bleyenbergh, Pascal; Peetermans, Willy E; Decramer, Marc

    2011-06-01

    This article analyzes patterns of consumption of fluoroquinolones and documents the in vitro resistances of Streptococcus pneumoniae isolates to fluoroquinolones in the ambulatory care setting in Belgium over time. The volume of fluoroquinolone consumption has fallen consistently since 2003. Fluoroquinolones were used primarily for their registered indications (i.e., urinary tract infections and lower respiratory tract infections). The MIC distributions of moxifloxacin and levofloxacin in S. pneumoniae isolates remained stable during 2004 to 2009, and the level of resistance to moxifloxacin and levofloxacin was low (≤1%).

  10. Fluoroquinolone-resistant Neisseria gonorrhoeae: the inevitable epidemic.

    PubMed

    Ghanem, Khalil G; Giles, Julie A; Zenilman, Jonathan M

    2005-06-01

    The worldwide incidence of fluoroquinolone-resistant Neisseria gonorrhoeae has increased dramatically in the last few years. Single doses of fluoroquinolones can no longer be used to treat N gonorrhoeae infections acquired in the Far East, parts of the Middle East, the Pacific Islands, and parts of Western Europe and the United States. Although California and Hawaii account for most of the current United States cases, the increased incidence of FQR in some high-risk groups independent of geography heralds an imminent spread of drug-resistant strains throughout the rest of the population. The use of molecular tests has revolutionized the diagnostic field in STIs. The main limitation of their application in N gonorrhoeae testing has been the loss of culture specimens that allow antimicrobial sensitivity testing. New molecular methods have made it possible to detect antimicrobial resistance without the use of live organisms. These tests hold the promise of improving epidemiologic tracking of N gonorrhoeae drug resistance, leading to better patient management at the local level. The loss of fluoroquinolones limits available oral regimens to a single CDC-recommended antibiotic, cefixime. Oral, inexpensive, single-dose alternatives are needed to ensure continued therapeutic success.

  11. Intractable Acute Pain Related to Fluoroquinolone-Induced Peripheral Neuropathy.

    PubMed

    Dukewich, Matthew; Danesh, Arash; Onyima, Chiemeka; Gupta, Anita

    2017-03-30

    Fluoroquinolones are widely prescribed antibiotics, used for various infectious etiologies. These antibiotics carry the possibility of the serious adverse effect of peripheral neuropathy, with a true incidence not known owing to its rare existence. Recently, the Food and Drug Administration (FDA) has required alterations to drug labels to highlight this adverse effect of fluoroquinolones. This is a case report of a single patient at an inpatient neurology service at an urban academic medical center in the United States. The patient is a 20-year-old male, with well-controlled type 1 diabetes mellitus, presenting with a short duration of bilateral lower extremity pain following a 10-day course of levofloxacin for suspected epididymitis. The patient was initially diagnosed with complex regional pain syndrome and treated with a variety of pain medications, including lidocaine infusions, hydromorphone, methadone, and ketamine infusions. After review of the patient's history and limited response to medical management, the patient's condition was reclassified as an adverse effect from fluoroquinolone treatment. Pain of unknown etiology can be perplexing, both for the physician and the patient. Reporting of similar incidents attributed to medication adverse effects will increase the awareness of this type of neuropathy, avoid future cases of misdiagnosis, and enable early detection and treatment.

  12. Removal of five fluoroquinolone antibiotics during broiler manure composting.

    PubMed

    Yang, Bing; Meng, Lei; Xue, Nandong

    2017-03-16

    Composting is a cost-effective approach for the removal of antibiotics from the environment; however, the consequence of this approach on fluoroquinolone antibiotics is limited. The fate of five representative fluoroquinolone antibiotics, namely ciprofloxacin, enrofloxacin, lomefloxacin, norfloxacin, and sarafloxacin, was investigated in a pilot-scale composting of broiler manure over 42 days. The effect of antibiotic concentrations (at a dose of 15, 30, or 60 mg/kg for each and a control without antibiotic addition) on the composting process was also assessed. The 42-day composting showed 45.3-75.4% of antibiotic removal with species-specific patterns. However, the observed variations in such removal among both antibiotics concentrations and composting times were not significant in most cases, possibly indicating a slight side-effect of the tested antibiotic concentrations on the composting process. To the best of our knowledge, this study is among few studies with a focus on the persistence of fluoroquinolone antibiotics during a pilot-scale composting, which warrants further study in regards to the mechanism underlying the removal of these compounds during composting.

  13. 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.

  14. Seeking to shed some light on the binding of fluoroquinolones to albumins.

    PubMed

    Bosca, Francisco

    2012-03-22

    Interactions between serum albumins (HSA, human, and BSA, bovine) and fluoroquinolones (FQs), such as enoxacin, norfloxacin, ciprofloxacin, and ofloxacin, have been studied using the laser flash photolysis technique. Lifetimes and quantum yields of FQs triplet excited states ((3)FQs) are not affected by the presence of albumins, however, the quenching of (3)FQs by tryptophan and tyrosine and the subsequent generation of FQs radical anions and tyrosyl or tryptophanyl radicals were detected. These results, besides agreeing with association constants (K(a)) for FQs binding to albumins lower than 6 × 10(2) M(-1), are highly relevant to understanding the process of photohapten formation, the first event in the onset of photoallergy. The emission of tryptophan within albumin is not affected by the presence of FQs when the inner filter effects (IFE) of these drugs are taken into account, which explains the discrepancies reported in the literature about K(a) of FQs with albumins.

  15. In vitro activity of eight fluoroquinolones against clinical isolates of Brucella melitensis.

    PubMed

    Qadri, S M; Akhter, J; Ueno, Y; Saldin, H

    1993-01-01

    Since fluoroquinolones have generated much interest because of their excellent in vitro and in vivo activity, their pharmacokinetic propertiesm oral dosing and intracellular penetration, we tested the susceptibility of 146 recent clinical isolated of Brucella melitensis agaist eight 4-quinolone drugs and five conventional drugs. The drugs tested included ciprofloxacin, norfloxacin, temafloxacin, sparfloxacin, fleroxacin, pefloxacin, lomefloxacin, CI-960, tetracycline, gentamicin, streptomycin rifampicin and trimethoprim-sulfamethoxazole. All the isolates were susceptible to the eight quinolones tested, with an MIC-90 ranging between 0.12 mg/L to 2.0 mg/L depending on the drug. Lowest MCIs were observed with CI-960 and highest temafloxacin and sparfloxacin. One isolate which had developed resistance to ciprofloxacin while the patient was being treated with this drug exhibited cross-resistance to all the members of the family.

  16. Sunlight-induced degradation of fluoroquinolones in wastewater effluent: Photoproducts identification and toxicity.

    PubMed

    Sturini, Michela; Speltini, Andrea; Maraschi, Federica; Pretali, Luca; Ferri, Elida Nora; Profumo, Antonella

    2015-09-01

    The photodegradation of Ciprofloxacin (CIP), Enrofloxacin (ENR), Danofloxacin (DAN), Marbofloxacin (MAR) and Levofloxacin (LEV), five widely used fluoroquinolones (FQs), was studied in urban WWTP secondary effluent, under solar light. The degradation profiles and the kinetic constants were determined at the micrograms per litre levels (20-50 μg L(-1)). The photo-generated products were identified by high-pressure liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). The toxicity of the photoproducts was assessed by Vibrio fischeri light emission inhibition assay performed on irradiated and not-irradiated FQs solutions, at environmentally significant concentrations. Attention was focused on the evaluation of the photoproducts contribution to the overall biotoxic effect of these emerging pollutants. Data from chronic exposure experiments (24-48 h) were primarily considered. Results confirmed the major usefulness of chronic toxicity data with respect to the acute assay ones and proved the not negligible biotoxicity of the FQs photodegradation products.

  17. STO-2: Support for 4th Year Operations, Recovery, and Science: Smithsonian Astrophysical Observatory Co-I

    NASA Astrophysics Data System (ADS)

    Stark, Antony

    The Lead Proposal for this investigation originates from the University of Arizona, Steward Observatory under Principal Investigator Dr. Christopher K. Walker. The Smithsonian Astrophysical Observatory (SAO) is pleased to submit this subsidiary proposal for engineering and scientific collaboration on the reflight of the Stratospheric TeraHertz Observatory (STO-2). This proposal covers Support for 4th Year Operations, Recovery, and Science as a result of the failure to launch due to weather in the 2015-2016 season. The Institutional Principal Investigator for the SAO effort is Antony A. Stark, and scientific Co-Investigators Gary Melnick, Volker Tolls, and Matthew Ashby. SAO will provide pre-flight engineering and flight monitoring support for the second Long Duration Flight (LDF) from McMurdo Sound in Antarctica. Subsequent to the flight, SAO Co-Is will contribute to data management and analysis, scientific interpretation, publication of results, and public distribution of data.

  18. 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

  19. 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.

  20. 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

  1. 4th Stage Transvaginal omental herniation during VBAC complicated by shoulder dystocia: a unique presentation of uterine rupture

    PubMed Central

    2013-01-01

    Background Uterine rupture is a common complication in women attempting their first virginal birth after caesarean section (VBAC) but the risk diminishes with subsequent VBACs. It occurs in rates of 0.5-9% and is influenced by various factors. Case presentation A unique case of uterine rupture in a Kenyan woman of African descent during a repeat VBAC complicated by shoulder dystocia was discovered during the 4th stage of labour when omentum was noted protruding through the vagina. She had delivered 4 years earlier by caesarean section. Conclusion It is not common to experience uterine rupture among women attempting repeat VBAC. When it occurs, it may not always follow the known pattern intra-partum and is often associated with poor foetal outcome. PMID:23521920

  2. 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.

  3. Occurrence of fluoroquinolones and fluoroquinolone-resistance genes in the aquatic environment.

    PubMed

    Adachi, Fumie; Yamamoto, Atsushi; Takakura, Koh-Ichi; Kawahara, Ryuji

    2013-02-01

    Fluoroquinolones (FQs) have been detected in aquatic environments in several countries. Long-term exposure to low levels of antimicrobial agents provides selective pressure, which might alter the sensitivity of bacteria to antimicrobial agents in the environment. Here, we examined FQ levels and the resistance of Escherichia coli (E. coli) to FQs by phenotyping and genotyping. In the aquatic environment in Osaka, Japan, ciprofloxacin, enoxacin, enfloxacin, lomefloxacin, norfloxacin, and ofloxacin were detected in concentrations ranging from 0.1 to 570 ng L(-1). FQ-resistant E. coli were also found. Although no obvious correlation was detected between the concentration of FQs and the presence of FQ-resistant E. coli, FQ-resistant E. coli were detected in samples along with FQs, particularly ciprofloxacin and ofloxacin. Most FQ-resistant E. coli carried mutations in gyrA, parC, and parE in quinolone resistance-determining regions. No mutations in gyrB were detected in any isolates. Amino acid changes in these isolates were quite similar to those in clinical isolates. Six strains carried the plasmid-mediated quinolone resistance determinant qnrS1 and expressed low susceptibility to ciprofloxacin and nalidixic acid: the minimum inhibitory concentrations ranged from 0.25 μg mL(-1) for ciprofloxacin, and from 8 to 16 μg mL(-1) for nalidixic acid. This finding confirmed that plasmids containing qnr genes themselves did not confer full resistance to quinolones. Because plasmids are responsible for much of the horizontal gene transfer, these genes may transfer and spread in the environment. To our knowledge, this is the first report of plasmid-mediated quinolone resistance determinant qnrS1 in the aquatic environment, and this investigation provides baseline data on antimicrobial resistance profiles in the Osaka area. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Ribavirin exerts differential effects on functions of Cd4+ Th1, Th2, and regulatory T cell clones in hepatitis C.

    PubMed

    Langhans, Bettina; Nischalke, Hans Dieter; Arndt, Simone; Braunschweiger, Ingrid; Nattermann, Jacob; Sauerbruch, Tilman; Spengler, Ulrich

    2012-01-01

    Ribavirin improves outcomes of therapy in chronic hepatitis C but its mode of action has still remained unclear. Since ribavirin has been proposed to modulate the host's T cell responses, we studied its direct effects on CD4(+) T cell clones with diverse functional polarization which had been generated from patients with chronic hepatitis C. We analysed in vitro proliferation ([(3)H] thymidine uptake) and cytokine responses (IL-10, IFN-gamma) at varying concentrations of ribavirin (0-10 µg/ml) in 8, 9 and 7 CD4(+) TH1, TH2 and regulatory T cell (Treg) clones, respectively. In co-culture experiments, we further determined effects of ribarivin on inhibition of TH1 and TH2 effector cells by Treg clones. All clones had been generated from peripheral blood of patients with chronic hepatitis C in the presence of HCV core protein. Ribavirin enhanced proliferation of T effector cells and increased production of IFN-gamma in TH1 clones, but had only little effect on IL-10 secretion in TH2 clones. However, ribavirin markedly inhibited IL-10 release in Treg clones in a dose dependent fashion. These Treg clones suppressed proliferation of T effector clones by their IL-10 secretion, and in co-culture assays ribavirin reversed Treg-mediated suppression of T effector cells. Our in vitro data suggest that--in addition to its immunostimulatory effects on TH1 cells--ribavirin can inhibit functions of HCV-specific Tregs and thus reverses Treg-mediated suppression of T effector cells in chronic hepatitis C.

  5. Estimates of premorbid ability in a neurodegenerative disease clinic population: comparing the Test of Premorbid Functioning and the Wide Range Achievement Test, 4th Edition.

    PubMed

    Berg, Jody-Lynn; Durant, January; Banks, Sarah J; Miller, Justin B

    2016-05-01

    Two frequently used measures to assess premorbid intellectual ability include the Wide Range Achievement Test, 4th Edition Reading Subtest (WRAT-4 READ) and the Test of Premorbid Functioning (TOPF). The present study compared estimates obtained from these measures in a neurodegenerative disease population. Records from 85 referrals seen for neuropsychological evaluation in a neurodegenerative disorders clinic were reviewed. Evaluations included TOPF, WRAT-4 READ, and measures of memory, reasoning, language, and executive functioning. Pairwise correlations and concordance correlation coefficients (CCC) were calculated between raw scores and predicted intelligence estimates. Discrepancy scores were calculated between estimates and data were divided into three groups based on size of standardized discrepancy score: Equal, WRAT-4 READ > TOPF, and TOPF > WRAT-4 READ. analysis of variances compared groups on demographic characteristics and cognitive performance. Despite strong Pearson correlation, CCC between predicted IQ estimates showed poor agreement between measures, with evidence of both fixed and proportional bias. Discrepancies ranged from -24.0 to 22.0 (M = 1.78, SD = 6.65), with TOPF generating higher estimates on average. Individuals performing better on WRAT-4 READ were significantly older (M age = 76.26, SD = 7.53) than those performing similarly on both measures and those performing better on TOPF (F (2, 82) = 7.31, p < .001). All other comparisons between groups on demographic variables and cognitive measures were non-significant. Estimates of premorbid intelligence obtained from the TOPF and WRAT-4 READ have a strong linear relationship, but systematically generate inconsistent estimates in a neurodegenerative disease clinical sample and should not be used interchangeably.

  6. Improved fluoroquinolone detection in ELISA through engineering of a broad-specific single-chain variable fragment binding simultaneously to 20 fluoroquinolones.

    PubMed

    Wen, Kai; Nölke, Greta; Schillberg, Stefan; Wang, Zhanhui; Zhang, Suxia; Wu, Congming; Jiang, Haiyang; Meng, Hui; Shen, Jianzhong

    2012-07-01

    Fluoroquinolones (FQs) are a group of synthetic, broad-spectrum antibacterial agents. Due to its extensive use in animal industry and aquaculture, residues of these antibiotics and the emergence of bacteria resistant to FQs have become a major public health issue. To prepare a generic antibody capable of recognizing nearly all FQs, a single-chain variable fragment (scFv) was generated from the murine hybridoma cells C49H1 producing a FQ-specific monoclonal antibody. This scFv was characterized by indirect competitive enzyme-linked immunosorbent assay (ciELISA), and it showed identical binding properties to parental monoclonal antibody: it was capable of recognizing 17 of 20 targeted FQs below maximum residue limits, except for sarafloxacin (SAR), difloxacin (DIF), and trovafloxacin (TRO) which are highly concerned members in the FQs family. In order to broaden the specificity of this scFv to SAR and its analogues (DIF and TRO), protein homology modeling and antibody-ligands docking analysis were employed to identify the potential key amino acid residues involved in hapten antibody. A mutagenesis phage display library was generated by site directed mutagenesis randomizing five aminoacid residues in the third heavy-chain complementarity determining region. After one round of panning against biotinylated norfloxacin (NOR) and four rounds of panning against biotinylated SAR, scFv variants we screened showed up to 10-fold improved IC(50) against SAR, DIF, and TRO in ciELISA while the specificity against other FQs was fully retained.

  7. [A development of Byzantine Christian charities during the 4(th)-7(th) centuries and the birth of the hospital].

    PubMed

    Nam, Sung Hyun

    2015-04-01

    This study aims to examine the beginning and the development of Christian Charities during the 4(th)-6(th) centuries which would eventually result in the birth of the hospital in modern sense in the first half of the 7(th) century. For this purpose, I looked carefully into various primary sources concerning the early Christian institutions for the poor and the sick. Above all, it's proper to note that the first xenodocheion where hospitality was combined with a systematic caring, is concerned with the Trinitarian debate of the 4(th) century. In 356, Eustathios, one of the leaders of homoiousios group, established xenodocheion to care for the sick and the lepers in Sebaste of Armenia, whereas his opponent Aetios, doctor and leader of the heteroousios party, was reckoned to have combined the medical treatment with his clerical activities. Then, Basil of Caesarea, disciple of Eustathios of Sebaste, also founded in 372 a magnificent benevolent complex named 'Basileias' after its founder. I scrupulously analysed several contemporary materials mentioning the charitable institution of Caesarea which was called alternatively katagogia, ptochotropheion, xenodocheion. John Chrysostome also founded several nosokomeia in Constantinople at the end of the 4(th) century and the beginning of the 5(th) century. Apparently, the contemporary sources mention that doctors existed for these Charities, but there is no sufficient proof that these 'Christian Hospitals,' Basileias or nosokomeia of Constantinople were hospitals in modern sense. Imperial constitutions began to mention ptochotropheion, xenodocheion and orphanotropheion since the second half of the 5(th) century and then some Justinian laws evoked nosokomium, brephotrophia, gerontocomia. These laws reveal that 'Christian Hospitals' were well clarified and deeply rooted in Byzantine society already in these periods. And then, new benevolent institutions emerged in the 6(th) century: nosokomeia for a specific class and

  8. Retrospective analysis of fluoroquinolone prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplantation.

    PubMed

    Simondsen, Katherine A; Reed, Michael P; Mably, Mary S; Zhang, Yang; Longo, Walter L

    2013-12-01

    Patients undergoing allogeneic hematopoietic stem cell transplant are at a high risk for infection-related mortality in the immediate post-transplantation phase. Prophylaxis with a fluoroquinolone is now recommended to reduce this risk with the stipulation that surveillance for increased fluoroquinolone resistance Clostridium difficile associated diarrhea be conducted. We conducted a retrospective chart review of 48 patients who underwent an allogeneic hematopoietic stem cell transplant and received a fluoroquinolone for prophylaxis and 48 patients who underwent an allogeneic hematopoietic stem cell transplant who did not receive a fluoroquinolone for prophylaxis. All patients received the same standard antifungal, antiviral and anti-pneumocystis prophylaxis. Patients receiving fluoroquinolone prophylaxis had a lower incidence of febrile neutropenia than those not receiving prophylaxis, though the difference was not found to be statistically significant (83% vs. 67%, p = 0.098). Similar non-significant improvements in the number of positive cultures recovered during an episode of febrile neutropenia and antimicrobial days were noted. No significant increase in fluoroquinolone resistance, Clostridium difficile associated diarrhea, or in methicillin resistant Staphylococcus aureus infections were noted. Our single institution experience with fluoroquinolone prophylaxis for allogeneic hematopoietic stem cell transplant patients supports continuation of this practice. Expansion to autologous hematopoietic stem cell transplant patients may be appropriate based on guideline recommendations and our institution-specific experience with fluoroquinolone prophylaxis.

  9. 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

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

    USDA-ARS?s Scientific Manuscript database

    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...

  11. Colonization with extraintestinal pathogenic Escherichia coli among nursing home residents and its relationship to fluoroquinolone resistance.

    PubMed

    Maslow, Joel N; Lautenbach, Ebbing; Glaze, Thomas; Bilker, Warren; Johnson, James R

    2004-09-01

    In a cross-sectional fecal prevalence survey involving 49 residents of a Veterans Affairs nursing home, 59% of subjects were colonized with extraintestinal pathogenic Escherichia coli (ExPEC), 22% were colonized with adhesin-positive E. coli, and 51% were colonized with fluoroquinolone-resistant E. coli. Among 80 unique isolates, adhesins correlated negatively and aerobactin correlated positively with fluoroquinolone resistance.

  12. DNA gyrase-mediated natural resistance to fluoroquinolones in Ehrlichia spp.

    PubMed

    Maurin, M; Abergel, C; Raoult, D

    2001-07-01

    Fluoroquinolone susceptibility heterogeneity between various Ehrlichia species has been previously demonstrated. In gram-negative bacteria, resistance to fluoroquinolones most often corresponds to specific amino acid variations in a portion of the protein sequence of the A subunit of DNA gyrase (GyrA), referred to as the quinolone resistance-determining region (QRDR). We suspected a similar mechanism to be responsible for natural resistance in some Ehrlichia species. To verify this hypothesis, we sequenced the entire gyrA gene of the quinolone-susceptible species Ehrlichia sennetsu and designed specific primers to amplify and sequence the QRDR of four other Ehrlichia species as well as the closely related species Cowdria ruminantium. We identified in the fluoroquinolone-resistant species Ehrlichia chaffeensis and Ehrlichia canis a specific GyrA QRDR amino acid sequence, also present in C. ruminantium (whose susceptibility to fluoroquinolones remains unknown). These three species belong to a single phylogenetic cluster referred to as the E. canis genogroup. A different GyrA QRDR pattern, shared by the Ehrlichia species representatives of the E. sennetsu and Ehrlichia phagocytophila genogroups, was identified. Three of the four species tested are known to be susceptible to fluoroquinolones. A serine residue in position 83 (Escherichia coli numbering) in the susceptible species is replaced by an alanine residue in fluoroquinolone-resistant species. These results are consistent with the current knowledge on fluoroquinolone resistance in other gram-negative bacteria. They are indicative of a natural gyrase-mediated resistance to fluoroquinolones in the E. canis genogroup.

  13. Oxidative transformation of fluoroquinolone antibacterial agents and structurally related amines by manganese oxide.

    PubMed

    Zhang, Huichun; Huang, Ching-Hua

    2005-06-15

    Various members of the popular fluoroquinolone antibacterial agents (FQs) have been frequently detected in municipal wastewater and surface water bodies in recent years. This study was conducted to gain a better understanding of the fate of FQs in the sediment-water environment. Seven FQs were examined for adsorptive and oxidative interactions with delta-MnO2 under environmental conditions and exhibited reactivity in the order of ciprofloxacin approximately enrofloxacin approximately norfloxacin approximately ofloxacin > lomefloxacin > pipemidic acid > flumequine. Four amines that are structurally related to the aniline and piperazine functional groups of FQs showed reactivity to oxidation by delta-MnO2 in the order of 1-phenylpiperazine > aniline > N-phenylmorpholine > 4-phenylpiperidine. Comparison among the above compounds clearly indicates thatthe piperazine moiety of FQs is the predominant adsorptive and oxidative site to MnO2. Product analyses showed that oxidation by MnO2 results in dealkylation and hydroxylation at the piperazine moiety of FQs, with the quinolone ring essentially intact. The reaction kinetics, reactivity comparison, and product characterization point to a surface reaction mechanism that likely begins with formation of a surface complex between FQ and the surface-bound MnIV, followed by oxidation at the aromatic N1 atom of FQ's piperazine moietyto generate an anilinyl radical intermediate. The radical intermediates subsequently undergo N-dealkylation, C-hydroxylation, and possibly coupling to yield a range of products. Even though the quinolone ring appears to be stable with respect to MnO2, it affects the overall reactivity and potentially product distribution of FQs via substituent effects. Results of this study strongly suggest that manganese oxides commonly present in soils will likely play an important role in the abiotic degradation of fluoroquinolone antibacterial agents in the environment.

  14. 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.

  15. Treating acute exacerbations of chronic bronchitis and community-acquired pneumonia: how effective are respiratory fluoroquinolones?

    PubMed

    Balter, M; Weiss, K

    2006-10-01

    To provide family physicians with a review of evidence supporting fluoroquinolone therapy for defined patient populations with acute exacerbations of chronic bronchitis (AECB) and community-acquired pneumonia (CAP). A MEDLINE search found surveillance studies, randomized controlled trials, outcome studies, and expert consensus opinion. Descriptions of patient populations for which fluoroquinolone therapy is recommended are based on level I and level III evidence. A growing body of evidence supports fluoroquinolones as first-choice agents for treatment of AECB or CAP patients with comorbidity or a recent history of antibiotic use. Judicious and targeted therapy using fluoroquinolones among patients at risk of infections of the lower respiratory tract should contribute to improved clinical outcomes and broader health care savings. Current data show clinical utility and cost-effectiveness of fluoroquinolones in lower respiratory tract infections. The most recently issued AECB and CAP guidelines now recommend these antimicrobial agents as first-choice agents for specific patient populations.

  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.

  17. [Resistance to fluoroquinolones in 2013: what are the consequences in internal medicine?].

    PubMed

    de Lastours, V; Fantin, B

    2014-09-01

    Because of their important qualities, fluoroquinolones are amongst the most prescribed antibiotics in the world. The corollary of this success is the rapid increase in resistance to fluoroquinolones, responsible for treatment failures. Moreover, fluoroquinolone-resistance is often accompanied by resistance to other classes of antibiotics. Currently, significant levels of resistance are found both in hospitals and in community settings, severely limiting possibilities for empirical use of fluoroquinolones. A major mechanism explaining the rapid emergence of resistance to fluoroquinolones is their specific impact on human microbiota and the selection of resistant strains in the microbiota, which seems to be an unavoidable ecological side effect. In order to preserve the efficiency of this important class of antibiotics, limiting their use and respecting good practice recommendations are essential.

  18. 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

  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.

  20. Increase in fluoroquinolone non-susceptibility among clinical Streptococcus pyogenes in Belgium during 2007-10.

    PubMed

    Van Heirstraeten, Liesbet; Leten, Gert; Lammens, Christine; Goossens, Herman; Malhotra-Kumar, Surbhi

    2012-11-01

    To study the temporal evolution of fluoroquinolone non-susceptibility among Streptococcus pyogenes during 2007-10 in Belgium. S. pyogenes (n = 4690) recovered from patients with tonsillopharyngitis or skin, wound or invasive infections were screened for fluoroquinolone non-susceptibility. A selection of fluoroquinolone-non-susceptible strains was investigated for resistance mechanisms: reserpine-sensitive efflux and mutations in topoisomerase genes parC and gyrA. Clonality was determined by emm typing. Fluoroquinolone non-susceptibility (ciprofloxacin MIC ≥2 mg/L) was identified in 535 (11.4%) of 4690 S. pyogenes recovered during 2007-10 in Belgium. The proportion of fluoroquinolone-non-susceptible S. pyogenes increased significantly from 4.3% (2008) to 10.9% (2009) to 21.6% (2010) and coincided with a significant increase in emm6 strains among fluoroquinolone-non-susceptible S. pyogenes. Ciprofloxacin MICs of 2-8 mg/L correlated with first-step ParC substitutions. Two high-level fluoroquinolone-resistant S. pyogenes strains (ciprofloxacin MICs 32 mg/L) showed second-step substitutions in GyrA (Ser-81→Phe or Tyr) in addition to first-step mutations in parC. Reserpine-sensitive efflux was not observed. We report an unprecedented increase in fluoroquinolone-non-susceptible S. pyogenes in Belgium, a country with high quinolone use, as well as emergence of two high-level fluoroquinolone-resistant S. pyogenes strains with second-step mutations in gyrA, warning us of the need for more prudent use of fluoroquinolones and for continued resistance surveillance.

  1. Application of Fluoroquinolone Resistance Score in Management of Complicated Urinary Tract Infections.

    PubMed

    Shah, Ansal; Justo, Julie Ann; Bookstaver, P Brandon; Kohn, Joseph; Albrecht, Helmut; Al-Hasan, Majdi N

    2017-05-01

    The fluoroquinolone resistance score (FQRS) predicts the probability of fluoroquinolone resistance with good discrimination. The score has been derived from patients with bloodstream infections caused by Gram-negative bacteria and is based on fluoroquinolone use within the past 6 months, among other clinical and health care exposure criteria. This study aims to examine the utility of the FQRS in patients with complicated urinary tract infections (cUTI) and determine whether extension of prior fluoroquinolone use to 12 months improves model discrimination. Adults with cUTI at Palmetto Health in central South Carolina, USA, from 1 April 2015 through 31 July 2015 were prospectively identified. Multivariate logistic regression was used to examine the association between prior fluoroquinolone use and resistance. Among 238 patients, 54 (23%) had cUTI due to fluoroquinolone-resistant bacteria. Overall, the median age was 66 years, 162 (68%) patients were women, and 137 (58%) patients had cUTI due to Escherichia coli Prior exposure to fluoroquinolones within 3 months (adjusted odds ratio [aOR], 23.4; 95% confidence interval [CI], 8.2 to 76.8; P < 0.001) and within 3 to 12 months (aOR, 13.2; 95% CI, 3.1 to 68.4; P < 0.001) was independently associated with fluoroquinolone resistance compared to no prior use. The area under the receiver operating characteristic curve for the FQRS increased from 0.73 to 0.80 when prior fluoroquinolone use was extended from 6 to 12 months. FQRSs of ≥2 and ≥3 had negative predictive values of 91% and 90%, respectively. The modified FQRS stratifies patients with cUTI on the basis of the predicted probability of fluoroquinolone resistance with very good discrimination. Application of the modified FQRS may improve antimicrobial utilization in patients with acute pyelonephritis. Copyright © 2017 American Society for Microbiology.

  2. [Associated factors to availability and use of electronic media in children from preschool to 4th grade].

    PubMed

    Camargo, Diana Marina; Orozco, Luis Carlos

    2013-01-01

    The increased availability of electronic media has changed the behavior in children and young people by encouraging sedentary lifestile, with health effects from a very young age. To characterize the availability and use of electronic media and its associated factors in children from preschool through 4 th grade. A cross-sectional study with cluster sampling was carried out. Parents filled out the demographic survey, the availability and use of electronic media at home and in the child´s room. Log-binomial regression models were applied to estimate prevalence ratios adjusted for the sampling. Seven hundred and ten parents answered. The average age of the children was 6.7 years and 49.7% were male. Factors such as the mother working out of the house and family income were positively associated with the availability of electronic media at home and in the child´s room. The availability of a TV, computer and console in the child´s room, contributes to longer use of these electronic media. Both, the male gender and age of the child, were positively associated with the availability and use of electronic media. This is the first study in Colombia that reports the availability and use of electronic media in children. It is clear that modern life encourages sedentary behavior from the earliest years of life, which has been associated with health problems from early childhood. Intervention studies are needed aimed at reducing these behaviors in our context.

  3. The 2nd to 4th digit ratio (2D:4D) and eating disorder diagnosis in women

    PubMed Central

    Smith, April Rose; Joiner, Thomas

    2010-01-01

    Eating disorders are more common in females than in males and are believed to be caused, in part, by biological and hormonal factors. Digit ratio or 2D:4D (the ratio of the 2nd to the 4th digit) is considered to be a proxy for prenatal testosterone (PT) and prenatal oestrogen (PE) exposure. However, how 2D:4D may be related to type of eating pathology is unknown. The relationship between 2D:4D and eating disorder diagnosis was investigated in recovered and currently eating disordered (n=31) and control (n=99) women. Mean 2D:4D ratio was significantly lower (indicating higher levels of PT and lower levels of PE) in anorexic (AN) compared to bulimic (BN) women, with controls intermediary. In eating disordered women, 2D:4D was positively and significantly related to current weight, lowest weight and current BMI, with strongest associations for right 2D:4D. Among women, low 2D:4D is related to AN and high 2D:4D to BN, suggesting a differential causal influence of prenatal sex hormones on later eating pathology. PMID:21765573

  4. 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.

  5. Quality of Education Predicts Performance on the Wide Range Achievement Test-4th Edition Word Reading Subtest

    PubMed Central

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

    2014-01-01

    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. PMID:25404004

  6. 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.

  7. 4th International Meeting on Single Nucleotide Polymorphism and Complex Genome Analysis. Various uses for DNA variations.

    PubMed

    Brookes, Anthony J

    2002-02-01

    At the 4th International Meeting on Single Nucleotide Polymorphism and Complex Genome Analysis (Stockholm, Sweden, 10th-14th October 2001), approximately 100 scientists from more than 20 nations undertook a probing review of latest developments in the field. Despite impressive and still ongoing activities towards SNP discovery and validation, plus efforts towards haplotype exploitation, it was clear that supporting technologies for genotyping are way behind where they need to be. Innate complexity and large variances in aspects of genome function together pose immense challenges that are difficult to surmount in the human situation. In contrast, studies in simpler organisms and population/evolutionary genetics studies are yielding important new insights. Breakthroughs that are being made in understanding the genetic etiology of complex disease tend to involve genes of larger effect or extremely well merited candidates. Linkage studies and proximal phenotypes are being recommended, though the best way forward is still hotly debated. Consequently, many diverse and ambitious projects are underway, from which the data itself will eventually show what is and is not possible.

  8. Identification of DRG-1 As a Melanoma-Associated Antigen Recognized by CD4+ Th1 Cells

    PubMed Central

    Kiniwa, Yukiko; Li, Jiang; Wang, Mingjun; Sun, Chuang; Lee, Jeffrey E.; Wang, Rong-Fu; Wang, Helen Y.

    2015-01-01

    Immunotherapy has emerged as a promising strategy for the treatment of metastatic melanoma. Clinical studies have demonstrated the feasibility of cancer immunotherapy using tumor antigens recognized by CD8+ T cells. However, the overall immune responses induced by these antigens are too weak and transient to induce tumor regression in the majority of patients who received immunization. A growing body of evidence suggests that CD4+ T helper (Th) cells play an important role in antitumor immunity. Therefore, the identification of MHC class II-restricted tumor antigens capable of stimulating CD4+ T cells may provide opportunities for developing effective cancer vaccines. To this end, we describe the identification of developmentally regulated GTP-binding protein 1 (DRG-1) as a melanoma-associated antigen recognized by HLA-DR11-restricted CD4+ Th1 cells. Epitope mapping analysis showed that the DRG1248-268 epitope of DRG-1 was required for T cell recognition. Reverse transcription-polymerase chain reaction revealed that DRG-1 was highly expressed in melanoma cell lines but not in normal tissues. DRG-1 knockdown by lentiviral-based shRNA suppressed melanoma cell proliferation and soft agar colony formation. Taken together, these data suggest that DRG-1 plays an important role in melanoma cell growth and transformation, indicating that DRG1 may represent a novel target for CD4+ T cell-mediated immunotherapy in melanoma. PMID:25993655

  9. [Experience with percutaneous endoscopic gastrostomy in the nutrition of a patient with 3rd and 4th degree facial burns].

    PubMed

    Halmy, C; Szücs, A; Gyökeres, T; Dékány, K; Mezeine, T I; Kertész, E

    1998-05-17

    Recovery after thermal injury depends in great proportion on nutrition. A major problem is accounted in patients with facial burn, because they can not be nourished per vias naturales. Eliminating disadvantages of parenteral nutrition, but utilizing the advantages of enteral nutrition, we have tried a new method of treatment in a patient whose case is presented. On the second day after injury a percutaneous endoscopic gastrostomy was made. On the 7th day after injury and on the 4th day from the beginning of enteral nutrition complete intake of food and liquid was assured through the percutaneous endoscopic gastrostoma. We had no complication related to the gastrostoma. Nutrition through the percutaneous endoscopic gastrostoma at our patient provided a "natural" route to assure liquid, electrolite and energy balance, prevented atrophy of intestinal mucosa and its metabolic and immunologic complications. With the use of percutaneous endoscopic gastrostoma the possible complications of central line catheter were omitted. Our opinion is that percutaneous endoscopic gastrostomy is a safe and effective method for the clinical nutrition of burned patients.

  10. Abnormal T cell receptor signal transduction of CD4 Th cells in X-linked lymphoproliferative syndrome.

    PubMed

    Nakamura, H; Zarycki, J; Sullivan, J L; Jung, J U

    2001-09-01

    The molecular basis of X-linked lymphoproliferative (XLP) disease has been attributed to mutations in the signaling lymphocytic activation molecule-associated protein (SAP), an src homology 2 domain-containing intracellular signaling molecule known to interact with the lymphocyte-activating surface receptors signaling lymphocytic activation molecule and 2B4. To investigate the effect of SAP defects on TCR signal transduction, herpesvirus saimiri-immortalized CD4 Th cells from XLP patients and normal healthy individuals were examined for their response to TCR stimulation. CD4 T cells of XLP patients displayed elevated levels of tyrosine phosphorylation compared with CD4 T cells from healthy individuals. In addition, downstream serine/threonine kinases are constitutively active in CD4 T cells of XLP patients. In contrast, TCR-mediated activation of Akt, c-Jun-NH(2)-terminal kinases, and extracellular signal-regulated kinases in XLP CD4 T cells was transient and rapidly diminished when compared with that in control CD4 T cells. Consequently, XLP CD4 T cells exhibited severe defects in up-regulation of IL-2 and IFN-gamma cytokine production upon TCR stimulation and in MLRs. Finally, SAP specifically interacted with a 75-kDa tyrosine-phosphorylated protein upon TCR stimulation. These results demonstrate that CD4 T cells from XLP patients exhibit aberrant TCR signal transduction and that the defect in SAP function is likely responsible for this phenotype.

  11. Laser flash photolysis study of photoionization in fluoroquinolones.

    PubMed

    Monti, Sandra; Sortino, Salvatore

    2002-11-01

    A laser flash photolysis investigation was carried out on the mechanism of electron photoejection in fluoroquinolone derivatives, bearing either electron donating or electron accepting substituents in position 8, laser excited at lambda(exc) = 355 nm in neutral aqueous solutions. The dependence of the hydrated electron absorption at 720 nm on the laser intensity and on the presence of N2O as electron scavenger evidenced that in enoxacin, norfloxacin, and lomefloxacin the photoionization is predominantly two-photon. With rufloxacin, besides the two-photon process, a one photon contribution with a quantum yield of 0.034 was measured.

  12. Degradation of the fluoroquinolone enrofloxacin by wood-rotting fungi.

    PubMed Central

    Martens, R; Wetzstein, H G; Zadrazil, F; Capelari, M; Hoffmann, P; Schmeer, N

    1996-01-01

    The veterinary fluoroquinolone enrofloxacin was degraded in vitro by four species of wood-rotting fungi growing on wetted wheat straw containing carbonyl-14C-labeled drug. A maximum 14CO2 production of 17% per week was observed with the brown rot fungus Gloeophyllum striatum, resulting in up to 53% after 8 weeks. However, rates reached at most 0.2 and 0.9% per week, if enrofloxacin was preadsorbed to native or gamma ray-sterilized soil, respectively. PMID:8900012

  13. Synthesis and Microbiological Evaluation of Novel Tetracyclic Fluoroquinolones.

    PubMed

    Wagman, Allan S; Cirz, Ryan; McEnroe, Glenn; Aggen, James; Linsell, Martin S; Goldblum, Adam A; Lopez, Sara; Gomez, Marcela; Miller, George; Simons, Lloyd J; Belliotti, Thomas R; Harris, Christina R; Poel, Toni-Jo; Melnick, Michael J; Gaston, Ricky D; Moser, Heinz E

    2017-09-07

    Conformationally-constrained tetracyclic fluoroquinolones (FQs) were synthesized and profiled for their microbiological spectrum. The installation of a 7-membered ring between the pyrrolidine substituents and the C8-position on the FQ core scaffold resulted in a remarkable enhancement of microbiological potency on both Gram-positive and Gram-negative bacteria. Focused optimization of 7-membered ring composition, stereochemistry, and amine placement led to the discovery of the two lead compounds that were selected for further progression. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  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. The St. Jude Cancer Education for Children Program Pilot Study: Determining the Knowledge Acquisition and Retention of 4th-Grade Students.

    PubMed

    Ayers, Katherine; Villalobos, Aubrey Van Kirk; Li, Zhenghong; Krasin, Matthew

    2016-03-01

    In 2006, St. Jude Children's Research Hospital began developing a school-based outreach program known as the St. Jude Cancer Education for Children Program (SJCECP). The program aimed to teach children about cancer and healthy habits that can prevent the formation of cancers into adulthood. During the 2010-2011 academic years, we conducted a pilot evaluation of the SJCECP curriculum, with the primary objective of evaluating the impact of the intervention on knowledge acquisition and retention among 4th-grade students participating in the program. Seven local schools and 481 students from the Memphis area participated in the program evaluation. The results of this study show that 4th-grade students are able to acquire gains in knowledge related to cells, cancer, and healthy living after receiving the SJCECP intervention. We conclude that the program can be a useful tool for improving knowledge of cancer concepts at the 4th-grade level.

  16. Impact of antibiotic use during hospitalization on the development of gastrointestinal colonization with Escherichia coli with reduced fluoroquinolone susceptibility.

    PubMed

    Han, Jennifer H; Bilker, Warren B; Nachamkin, Irving; Tolomeo, Pam; Mao, Xiangqun; Fishman, Neil O; Lautenbach, Ebbing

    2013-10-01

    Infections due to fluoroquinolone-resistant Escherichia coli (FQREC) are associated with significant morbidity and mortality. Fluoroquinolone resistance likely arises at the level of gastrointestinal colonization. The objective of this study was to identify risk factors for the development of FQREC gastrointestinal tract colonization in hospitalized patients, including the impact of antibiotics prescribed during hospitalization. A prospective cohort study was conducted from 2002 to 2004 within a university health system. Hospitalized patients initially colonized with fluoroquinolone-susceptible E. coli were followed up with serial fecal sampling for new FQREC colonization or until hospital discharge or death. A Cox proportional hazards regression model was developed to identify risk factors for new FQREC colonization, with antibiotic exposure modeled as time-varying covariates. Of 395 subjects, 73 (18.5%) became newly colonized with FQREC. Length of stay before sampling (hazard ratio [HR], 1.02 [95% confidence interval (CI), 1.1-1.03]; P = .003) and malignancy (HR, 0.37 [95% CI, 0.21-0.67]; P = .001) were significantly associated with the development of FQREC colonization. In addition, receipt of a first-generation cephalosporin (HR, 1.19 [95% CI, 1.10-1.29]; P < .001) or cefepime (HR, 1.05 [95% CI, 1.00-1.10]; P = .048) during hospitalization increased the risk of new FQREC colonization. The acquisition of FQREC in the hospital setting is complex, and antimicrobial stewardship programs should take into account patterns of antibiotic use in implementing strategies to reduce the development of new FQREC colonization. Future studies are needed to identify risk factors for infection in hospitalized patients newly colonized with FQREC.

  17. Impact of Antibiotic Use during Hospitalization on the Development of Gastrointestinal Colonization with Escherichia coli with Reduced Fluoroquinolone Susceptibility

    PubMed Central

    Han, Jennifer H.; Bilker, Warren B.; Nachamkin, Irving; Tolomeo, Pam; Mao, Xiangqun; Fishman, Neil O.; Lautenbach, Ebbing

    2014-01-01

    OBJECTIVE Infections due to fluoroquinolone-resistant Escherichia coli (FQREC) are associated with significant morbidity and mortality. Fluoroquinolone resistance likely arises at the level of gastrointestinal colonization. The objective of this study was to identify risk factors for the development of FQREC gastrointestinal tract colonization in hospitalized patients, including the impact of antibiotics prescribed during hospitalization. DESIGN A prospective cohort study was conducted from 2002 to 2004 within a university health system. METHODS Hospitalized patients initially colonized with fluoroquinolone-susceptible E. coli were followed up with serial fecal sampling for new FQREC colonization or until hospital discharge or death. A Cox proportional hazards regression model was developed to identify risk factors for new FQREC colonization, with antibiotic exposure modeled as time-varying covariates. RESULTS Of 395 subjects, 73 (18.5%) became newly colonized with FQREC. Length of stay before sampling (hazard ratio [HR], 1.02 [95% confidence interval (CI), 1.1–1.03]; P = .003) and malignancy (HR, 0.37 [95% CI, 0.21–0.67]; P = .001) were significantly associated with the development of FQREC colonization. In addition, receipt of a first-generation cephalosporin (HR, 1.19 [95% CI, 1.10–1.29]; P < .001) or cefepime (HR, 1.05 [95% CI, 1.00–1.10]; P = .048) during hospitalization increased the risk of new FQREC colonization. CONCLUSIONS The acquisition of FQREC in the hospital setting is complex, and antimicrobial stewardship programs should take into account patterns of antibiotic use in implementing strategies to reduce the development of new FQREC colonization. Future studies are needed to identify risk factors for infection in hospitalized patients newly colonized with FQREC. PMID:24018924

  18. Exploration of fluoroquinolone resistance in Streptococcus pyogenes: comparative structure analysis of wild-type and mutant DNA gyrase.

    PubMed

    Shafreen, Raja Mohmed Beema; Selvaraj, Chandrabose; Singh, Sanjeev Kumar; Pandian, Shunmugiah Karutha

    2013-06-01

    Quinolone resistance-determining region is known to be the druggability site of the target protein that undergoes frequent mutation and thus renders quinolone resistance. In the present study, ligands were tested for their inhibitory activity against DNA gyrase of Streptococcus pyogenes involved in DNA replication. In silico mutational analysis on modelled gyrase A revealed that GLU85 had the most possible interactions with all the ligands used for the study. The amino acid residue GLU85 had also been predicted with an essential role of maintaining the three-dimensional structure of the protein. When introduced with a mutation (GLU 85 LYS) on this particular residue, it had readily denatured the whole α-helix (from 80 to 90 amino acids). This was confirmed through the molecular dynamics simulation and revealed that this single mutation can cause many functional and structural changes. Furthermore, LYS85 mutation has altered the original secondary structure of the protein, which in turn led to the steric hindrance during the ligand-receptor interaction. The results based on the G-score revealed that ligands have reduced interaction with the mutant protein. The semisynthetic fluoroquinolone 6d, which is an exception, forms a strong interaction with the mutant protein and was experimentally verified using the antimicrobial test. Hence, the present study unravels the fact that mutation at the drug binding site is the major cause for different level of resistance by the S. pyogenes when exposed against the varying concentrations of the fluoroquinolones. Furthermore, a comparative assessment of quinolone derivative with the older generation fluoroquinolones will be of great impact for S. pyogenes-related infections. Copyright © 2013 John Wiley & Sons, Ltd.

  19. 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.

  20. Diagnosis of Drug Resistance to Fluoroquinolones, Amikacin, Capreomycin, Kanamycin and Ethambutol with Genotype MTBDRsl Assay: a Meta-Analysis.

    PubMed

    Mao, Xiaolu; Ke, Zunqiong; Shi, Xiaoyan; Liu, Shuiyi; Tang, Beibei; Wang, Jin; Huang, Hao

    2015-01-01

    The Genotype MTBDRsl is a new-generation PCR-based line-probe assay for rapid identification of the resistance to the second-line antituberculosis drugs with a single strip. The aim of this meta-analysis was to evaluate the performance of Genotype MTBDRsl in detecting drug resistance to fluoroquinolones, amikacin, capreomycin, kanamycin and ethambutol in comparison with the phenotypic drug susceptibility test. We searched Pubmed, Embase and the Cochrane Library and calculated the sensitivity, the specificity, the positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), corresponding 95% confidence interval (CI), and the area under the summary receiver operating characteristic (SROC) curves (AUC), and tested heterogeneity in accuracy estimates with the Spearman correlation coefficient and Chi-square. The summarized sensitivity (95% CI), specificity (95% CI), and AUC (standard error) were 0.869 (0.847-0.890), 0.973 (0.965-0.979) and 0.9690 (0.0188) for fluoroquinolones, 0.868 (0.829-0.900), 0.998 (0.994-0.999) and 0.9944 (0.0050) for amikacin, 0.879 (0.838-0.914), 0.970 (0.958-0.978) and 0.9791 (0.0120) for capreomycin, 0.501 (0.461-0.541), 0.991 (0.983-0.996) and 0.9814 (0.0114) for kanamycin and 0.686 (0.663-0.709), 0.871 (0.852-0.888) and 0.7349 (0.0639) for ethambutol, respectively. The genotype MTBDRsl demonstrate excellent accuracy for detecting drug resistance to fluoroquinolones, amikacin, and capreomycin, but it may not be an appropriate choice for detection of kanamycin and ethambutol. © 2015 by the Association of Clinical Scientists, Inc.

  1. [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.

  2. Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Odontogenic and Maxillofacial Bone Tumors.

    PubMed

    Wright, John M; Vered, Marilena

    2017-03-01

    The 4th edition of the World Health Organization's Classification of Head and Neck Tumours was published in January of 2017. This article provides a summary of the changes to Chapter 4 Tumours of the oral cavity and mobile tongue and Chapter 8 Odontogenic and maxillofacial bone tumours. Odontogenic cysts which were eliminated from the 3rd 2005 edition were included in the 4th edition as well as other unique allied conditons of the jaws. Many new tumors published since 2005 have been included in the 2017 classification.

  3. Fluoroquinolone-associated anaphylaxis in spontaneous adverse drug reaction reports in Germany: differences in reporting rates between individual fluoroquinolones and occurrence after first-ever use.

    PubMed

    Sachs, Bernhardt; Riegel, Stefan; Seebeck, Jörg; Beier, Rainer; Schichler, Dagmar; Barger, Antina; Merk, Hans F; Erdmann, Stephan

    2006-01-01

    The frequency of fluoroquinolone-associated anaphylaxis has been estimated to be 1.8-23 per 10 million days of treatment based on spontaneous reports. It is unknown whether there are differences between the reporting rates of anaphylaxis with individual fluoroquinolones. According to pathophysiology, anaphylaxis may be immune mediated (anaphylactic) or not (anaphylactoid). The latter may occur after first-ever intake since no sensitisation phase is necessary. To analyse spontaneous reports of fluoroquinolone-associated anaphylaxis contained in the spontaneous adverse drug reaction database of the Federal Institute for Drugs and Medical Devices in Germany with regard to differences in reporting rates between various fluoroquinolones, the previous intake and the time to onset of the reaction. All fluoroquinolone-associated cases of anaphylaxis, anaphylactic shock, and anaphylactic/anaphylactoid reaction spontaneously reported to the Federal Institute for Drugs and Medical Devices between 1 January 1993 and 31 December 2004 were identified and assessed with regard to the correctness of the diagnosis of anaphylaxis, the causal relationship with the drug, the previous intake of fluoroquinolones and the time to onset of the reaction. In 166 of 204 cases identified, the diagnosis of anaphylaxis and a causal relationship with the drug were considered at least possible. Moxifloxacin, levofloxacin, ciprofloxacin and ofloxacin accounted for 90 (54%), 25 (15%), 21 (13%) and 16 (10%) of the 166 cases, respectively. The corresponding reporting rates per 1 million defined daily doses based on crude estimates of exposure were 3.3, 0.6, 0.2 and 0.2 for moxifloxacin, levofloxacin, ciprofloxacin and ofloxacin, respectively. The occurrence of anaphylaxis after the first dose or within the first three days was reported in 71 of 166 (43%) cases, but no information on prior exposure with this or any other fluoroquinolone was provided with these reports. In 21 of 166 (13%) cases, the

  4. Campylobacter and fluoroquinolones: a bias data set?

    PubMed

    Silley, Peter

    2003-04-01

    always been the case for isolation of Campylobacter spp., however, we know that the antibiotic cocktails used in media over the last 10 years have changed and indeed there was a time when the filtration protocol which didn't use antibiotics was more widely used. As most reports in the literature do not state what methods were used to isolate Campylobacter spp. it is not possible to quantify any relationship between antibiotics used in the isolation media and susceptibility data. An approved method for Campylobacter susceptibility testing was not available until May 2002, all data generated prior to this date will have been generated using non-standard methods. As tremendous variability in the reproducibility data for Campylobacter spp. was observed during the development of the standard agar dilution susceptibility method, data generated with disk diffusion and broth microdilution methods must be considered with caution. It has been shown that, compared with the conventional agar dilution method, the E-test tends to give rise to lower minimal inhibitory concentrations (MICs) for sensitive strains and higher MICs for resistant strains. There are no recommended antibiotic breakpoint concentrations for Campylobacter spp. A breakpoint is used to separate sensitive from resistant strains of bacteria and is thus crucial to any discussion of antibiotic resistance. This discussion is further complicated by introduction of the terms microbiological and clinical breakpoints. While a microbiological breakpoint can be a useful parameter with regard to identifying resistance factors it cannot on its own be used to predict whether that bacteria will respond to treatment from an appropriate antibiotic. Predicting clinical response is a function of the clinical breakpoint which considers the pharmacokinetic profile of the antimicrobial compound, i.e. the concentration of the antimicrobial compound in the body and the MIC. The National Committee for Clinical Laboratory Standards (NCCLS

  5. Effect of magnesium complexation by fluoroquinolones on their antibacterial properties.

    PubMed

    Lecomte, S; Baron, M H; Chenon, M T; Coupry, C; Moreau, N J

    1994-12-01

    By using infrared and 19F nuclear magnetic resonance spectroscopies, we localized the binding site and measured the affinity of magnesium for six fluoroquinolones. It was proven that magnesium is situated between the ketone and the carboxylate groups. We determined the binding constants for the 1:1 Mg(2+)-drug complex in solution. Sparfloxacin and pefloxacin, with affinity constants (Ka) of (10.1 +/- 0.6) x 10(2) M-1 and (21 +/- 1) x 10(2) M-1, respectively, were the least and the most bound, respectively. The trend of the affinities of the assayed fluoroquinolones for magnesium was correlated with their antimicrobial activities against four bacteria and with their accumulation by these bacteria. The reference strain, Escherichia coli KL16, and two resistant mutants, NalA (gyrase mutation) and NalB (uptake defect), plus Staphylococcus aureus 209P were used. It appeared that, in every case, an impairment of accumulation is responsible for the increase in the MICs observed upon the addition of magnesium.

  6. Effect of magnesium complexation by fluoroquinolones on their antibacterial properties.

    PubMed Central

    Lecomte, S; Baron, M H; Chenon, M T; Coupry, C; Moreau, N J

    1994-01-01

    By using infrared and 19F nuclear magnetic resonance spectroscopies, we localized the binding site and measured the affinity of magnesium for six fluoroquinolones. It was proven that magnesium is situated between the ketone and the carboxylate groups. We determined the binding constants for the 1:1 Mg(2+)-drug complex in solution. Sparfloxacin and pefloxacin, with affinity constants (Ka) of (10.1 +/- 0.6) x 10(2) M-1 and (21 +/- 1) x 10(2) M-1, respectively, were the least and the most bound, respectively. The trend of the affinities of the assayed fluoroquinolones for magnesium was correlated with their antimicrobial activities against four bacteria and with their accumulation by these bacteria. The reference strain, Escherichia coli KL16, and two resistant mutants, NalA (gyrase mutation) and NalB (uptake defect), plus Staphylococcus aureus 209P were used. It appeared that, in every case, an impairment of accumulation is responsible for the increase in the MICs observed upon the addition of magnesium. Images PMID:7695267

  7. 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

  8. Fluoroquinolone resistance in Streptococcus pneumoniae from a university hospital, Thailand.

    PubMed

    Srifuengfung, Somporn; Tribuddharat, Chanwit; Chokephaibulkit, Kulkanya; Comerungsee, Sopita

    2010-11-01

    The most frequent markers of fluoroquinolone resistance in S. pneumoniae are chromosomal mutations in the quinolone-resistance-determining regions of DNA gyrase and topoisomerase IV encoding for the gyrA, gyrB and parC, parE genes. In 2008, 6.5% of the Streptococcus pneumoniae isolates in a Bangkok university hospital were resistant to ofloxacin. Using PCR and DNA sequencing, we identified mutations in both the gyrA and parC genes of four ofloxacin- and ciprofloxacin-resistant S. pneumoniae isolates (minimum inhibitory concentrations > 32 microg/ml). Mutations were found in the gyrA gene at positions Ser81Phe, Glu85Gly, Glu85Lys and in the parC gene at position Ser79Tyr. Three isolates had mutations in both genes. Two of the isolates were serotype 6B and two were serotypes not contained in currently licensed pneumococcal vaccines. This is the first report of the mechanisms of fluoroquinolone resistance in S. pneumoniae in Thailand.

  9. Fluoroquinolones and risk for methicillin-resistant Staphylococcus aureus, Canada.

    PubMed

    LeBlanc, Louiselle; Pépin, Jacques; Toulouse, Krystel; Ouellette, Marie-France; Coulombe, Marie-Andrée; Corriveau, Marie-Pier; Alary, Marie-Eve

    2006-09-01

    Receipt of fluoroquinolones was the predominant risk factor for Clostridium difficile-associated disease (CDAD) during an epidemic in Quebec, Canada. To determine the role of antimicrobial drugs in facilitating healthcare-associated methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection and to compare this role with their effects on methicillin-susceptible S. aureus infection and CDAD, we conducted a retrospective cohort study of patients in a Quebec hospital. For 7371 episodes of care, data were collected on risk factors, including receipt of antimicrobial drugs. Crude and adjusted hazard ratios (AHR) were calculated by Cox regression. Of 150 episodes of MRSA colonization and 23 of MRSA infection, fluoroquinolones were the only antimicrobials that increased risk for colonization (AHR 2.57, 95% confidence interval [CI] 1.84-3.60) and infection (AHR 2.49, 95% CI 1.02-6.07). Effect of antimicrobial drugs on MRSA colonization and infection was similar to effect on CDAD and should be considered when selecting antimicrobial drugs to treat common infections.

  10. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. 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

  12. 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.

  13. Promoting sustainable community service in the 4th year of medical school: a longitudinal service-learning elective.

    PubMed

    Jones, Kohar; Blinkhorn, Laura M; Schumann, Sarah-Anne; Reddy, Shalini T

    2014-01-01

    To address the country's most pressing healthcare needs, medical students must choose careers in primary care and commit to working with underserved populations. Involvement in student service organizations has been shown to strengthen leadership, empathy, and commitment to underserved health and may lead students to pursue careers in primary care. In 2010, the University of Chicago Pritzker School of Medicine developed a novel 1-year longitudinal service-learning elective called SERVE (Service, Education, Reflection, Volunteerism Elective). Students earned elective credit for completing three course requirements: 10 service sessions, monthly reflections, and a service-learning project. One third of the class enrolled in the course (33/99), 25 students completed the course, and 20 completed the final evaluation. Both quantitative and qualitative analyses of the final evaluations demonstrated high satisfaction with the course, and appreciation of the opportunity to volunteer, teach, and develop service projects. SERVE students reported a strong commitment to continuing community service after graduation, with 100% planning to continue volunteering and 70% strongly agreeing with the statement that they would practice in an underserved community in the future. This commitment was higher than that expressed by the graduating class of 2012 (34%) and higher compared to a national average (30.9%). SERVE is a unique 1-year course that reengages 4th-year medical students in service to their communities in a structured educational environment. SERVE students report that the course has increased their involvement in the community, supported their growth into a teaching role, and enhanced continuity within student-run free clinics. Future directions include assessing the impact of SERVE students on the experience of preclinical medical students in student-run free clinics; community response to SERVE projects; and the impact of SERVE on volunteerism, primary care specialty

  14. Relationship of workplace violence and perpetrators on sleep disturbance-data from the 4th Korean working conditions survey.

    PubMed

    Yoo, Taejun; Ye, Byeongjin; Kim, Jung-Il; Park, Siwoo

    2016-01-01

    The present study analyzed relationship of workplace violence and perpetrators of violence on sleep disturbance among wage workers in Korea. The present study used data from the 4th Korean Working Conditions Survey (KWCS) of 2014 in selecting a total of 25,138wage workers as the study population, which excluded those who failed or refused to respond to questions required for the present study. The workplace violence experience group included people who satisfied at least one of six relevant criteria (verbal abuse, unwanted sexual atte