Anisotropic contrast optical microscope.

An optical microscope is described that reveals contrast in the Mueller matrix images of a thin, transparent, or semi-transparent specimen located within an anisotropic object plane (anisotropic filter). The specimen changes the anisotropy of the filter and thereby produces contrast within the Mueller matrix images. Here we use an anisotropic filter composed of a semi-transparent, nanostructured thin film with sub-wavelength thickness placed within the object plane. The sample is illuminated as in common optical microscopy but the light is modulated in its polarization using combinations of linear polarizers and phase plate (compensator) to control and analyze the state of polarization. Direct generalized ellipsometry data analysis approaches permit extraction of fundamental Mueller matrix object plane images dispensing with the need of Fourier expansion methods. Generalized ellipsometry model approaches are used for quantitative image analyses. These images are obtained from sets of multiple images obtained under various polarizer, analyzer, and compensator settings. Up to 16 independent Mueller matrix images can be obtained, while our current setup is limited to 11 images normalized by the unpolarized intensity. We demonstrate the anisotropic contrast optical microscope by measuring lithographically defined micro-patterned anisotropic filters, and we quantify the adsorption of an organic self-assembled monolayer film onto the anisotropic filter. Comparison with an isotropic glass slide demonstrates the image enhancement obtained by our method over microscopy without the use of an anisotropic filter. In our current instrument, we estimate the limit of detection for organic volumetric mass within the object plane of ≈49 fg within ≈7 × 7 µm2 object surface area. Compared to a quartz crystal microbalance with dissipation instrumentation, where contemporary limits require a total load of ≈500 pg for detection, the instrumentation demonstrated here improves sensitivity to a total mass required for detection by 4 orders of magnitude. We detail the design and operation principles of the anisotropic contrast optical microscope, and we present further applications to the detection of nanoparticles, to novel approaches for imaging chromatography and to new contrast modalities for observations on living cells.

Outcomes associated with a thrice-weekly antimicrobial stewardship programme in a 253-bed community hospital.

WHAT IS KNOWN AND OBJECTIVES: Antimicrobial stewardship programmes (ASPs) have been shown to decrease antimicrobial resistance, reduce hospital-acquired infections and decrease overall antimicrobial expenditures. At St. Joseph Medical Center in Bellingham, WA, a thrice-weekly ASP was initiated in 2010 with the goals of decreasing carbapenem, fluoroquinolone and vancomycin use and tailoring duration of therapy. METHODS: Antibiotic use per 1000 patient-days and carbapenem, fluoroquinolone and vancomycin use were evaluated pre- and post-implementation of the ASP. Total antimicrobial expenditures were evaluated for the 3 years prior to ASP implementation and three years following implementation. RESULTS AND DISCUSSION: Antimicrobial days of therapy per 1000 patient-days declined by 6·4% after implementation of our ASP. There was a 37% reduction in total antimicrobial expenditures after implementation. Carbapenems, vancomycin and levofloxacin use decreased considerably. Ciprofloxacin use increased during the same time period. WHAT IS NEW AND CONCLUSION: A thrice-weekly, pharmacist-driven ASP can decrease antimicrobial expenditure, shorten duration of therapy and decrease the utilization of carbapenems, vancomycin and levofloxacin.

A single immunization with a dry powder anthrax vaccine protects rabbits against lethal aerosol challenge.

Here we confirm that intranasal (IN) dry powder anthrax vaccine formulations are able to protect rabbits against aerosol challenge 9 weeks after a single immunization. The optimum dose of rPA in our dry powder anthrax vaccine formulation in rabbits was experimentally determined to be 150microg and therefore was chosen as the target dose for all subsequent experiments. Rabbits received a single dose of either 150microg rPA, 150microg rPA+150microg of a conjugated 10-mer peptide representing the Bacillus anthracis capsule (conj), or 150microg of conj alone. All dry powder formulations contained MPL and chitosan (ChiSys). Significant anti-rPA titers and anthrax lethal toxin neutralizing antibody (TNA) levels were seen with both rPA containing vaccines, although rPA-specific IgG and TNA levels were reduced in rabbits immunized with rPA plus conj. Nine weeks after immunization, rabbits were exposed to a mean aerosol challenge dose of 278 LD50 of Ames spores. Groups immunized with rPA or with rPA+conj had significant increases in survivor proportions compared to the negative control group by Logrank test (p=0.0001 and 0.003, respectively), and survival was not statistically different for the rPA and rPA+conj immunized groups (p=0.63). These data demonstrate that a single immunization with our dry powder anthrax vaccine can protect against a lethal aerosol spore challenge 9 weeks later.

Levofloxacin: a therapeutic review.

This therapeutic review discusses the pharmacology, pharmacokinetics, in vitro activity, drug interactions, and adverse effects of levofloxacin, a fluoroquinolone antibiotic. Particular emphasis is placed on the clinical efficacy of levofloxacin and its place in therapy. Compared with ciprofloxacin and the earlier quinolone agents, levofloxacin has an improved pharmacokinetic profile that allows convenient once-daily dosing in either an oral or parenteral formulation. Levofloxacin has enhanced activity against gram-positive aerobic organisms, including penicillin-resistant pneumococci. In published comparative trials involving commonly used treatment regimens, levofloxacin had equivalent if not greater activity in the treatment of community-acquired pneumonia, acute bacterial exacerbations of chronic bronchitis, acute bacterial sinusitis, acute pyelonephritis, and complicated urinary tract infection. Levofloxacin is well tolerated and induces minimal adverse drug reactions. Based on the above attributes, it may be reasonable to include levofloxacin on the hospital formulary in place of older quinolones. More recently released quinolones such as trovafloxacin exhibit similar advantages; however, until direct comparative trials between levofloxacin and these newer agents are conducted, it is difficult to advocate one agent over another. Regardless of which quinolone is the primary agent on the formulary, it is imperative that this class of antimicrobial drugs be used with discretion to minimize the development of resistance.

Mefluidide effects on smooth brome composition and grazing cow-calf performance.

Mefluidide, a plant growth regulator, was evaluated in two cow-calf grazing trials and one herbage trial on smooth brome (Bromus inermis) pastures stocked at recommended densities in eastern Nebraska. Mefluidide-treated pasture increased cow and calf production during August of 1982 (P = .03) and calf production was greater during July of 1983 (P = .09). Mefluidide-treated smooth brome pastures increased calf production over the 1982 grazing season (P = .11) and cow gain over the 1982 (P = .12) and 1983 grazing seasons (P = .13). Mefluidide decreased neutral detergent fiber (NDF) content and increased crude protein content of smooth brome during both years (P less than .05), and increased in vitro dry matter disappearance (IVDMD) in 1982 (P less than .05). In ungrazed smooth brome, mefluidide treatment appeared to shift dry matter production to green leaves from green stem and brown leaf and stem fractions. Cell wall components [NDF, acid detergent fiber (ADF) and lignin] of green leaves were not affected significantly by mefluidide treatment, although green stems treated with mefluidide were lower in ADF and lignin (P less than .05).