Potential vorticity mixing by marginally unstable baroclinic disturbances

The weakly nonlinear dynamics of a baroclinic wave in a two-layer model near minimum critical shear is described in terms of a nonlinear critical layer problem which is completely integrable in the absence of dissipation. Sufficiently small amplitude supercritical inviscid disturbances are found to equilibrate to leading order, even though the absolute potential enstrophy of the lowest layer is always transient and transferred irreversibly to smaller and smaller scales. The inviscid equilibrium amplitude of the fundamental is found to be larger by a factor of 2 than the weakly dissipative value found by Pedlosky, implying that the limits t [RIGHTWARDS ARROW] ∞ and vanishing dissipation are not interchangeable. The fundamental equilibrates when the mixing in the lowest layer results in the streamwise homogenization of the coarse-grained potential vorticity. It is also noted that coarse-grain homogenization can be established on faster time scales than the fine-grain versions discussed by Rhines and Young. With weak or vanishing supercriticality or larger initial disturbance amplitudes, the fundamental may either equilibrate or oscillate periodically, depending on the form and strength of the initial disturbance. In the oscillating case, the baroclinic vortex reversibly wraps up and un-wraps and there is no tendency to mix potential vorticity. Finally, the possibility of further instabilities similar to those discussed by Killworth and McIntyre, and Haynes for the Rossby wave critical layer problem is also noted

Statistical analyses of correlation between fluconazole MICs for Candida spp. assessed by standard methods set forth by the European Committee on Antimicrobial Susceptibility Testing (E.Dis. 7.1) and CLSI (M27-A2).

The European Committee on Antimicrobial Susceptibility Testing (EUCAST) Subcommittee on Antifungal Susceptibility Testing recently published a standard for determining the susceptibility of fermentative yeasts to antifungals. From the beginning, the EUCAST and its North American counterpart, the CLSI, decided to work together in order to establish common standards. As part of this exercise, the susceptibility of a set of 475 yeast isolates was tested by both standards. The intraclass correlation coefficient and the equations defining the linear regression between both methods were estimated. Both methods produced very similar results, with an intraclass correlation coefficient of 0.954 (0.945 to 0.962), although linear regression analysis shows that the EUCAST standard resulted in slightly lower MICs. There were only eight isolates showing at least four twofold dilution MIC differences between both standards. After 24 h of incubation, the MICs obtained by the CLSI method were equivalent to those obtained by the EUCAST standard. In summary, both methods produce very similar MICs, indicating that methodology does not pose any obstacle to obtaining uniform standards for antifungal susceptibility testing of yeast

Rotational Evolution During Type I X-Ray Bursts

The rotation rates of six weakly-magnetic neutron stars accreting in low-mass X-ray binaries have most likely been measured by Type I X-ray burst observations with RXTE. The nearly coherent oscillations detected during the few seconds of thermonuclear burning are most simply understood as rotational modulation of brightness asymmetries on the neutron star surface. We show that, as suggested by Strohmayer and colleagues, the frequency changes of 1-2 Hz observed during bursts are consistent with angular momentum conservation as the burning shell hydrostatically expands and contracts. We calculate how vertical heat propagation through the radiative outer layers of the atmosphere and convection affect the coherence of the oscillation. We show that the evolution of the rotational profile depends strongly on whether the burning layers are composed of pure helium or mixed hydrogen/helium. Our results help explain the absence (presence) of oscillations from hydrogen-burning (helium-rich) bursts that was found by Muno and collaborators. We investigate angular momentum transport within the burning layers and the recoupling of the burning layers with the star. We show that the Kelvin-Helmholtz instability is quenched by the strong stratification, and that mixing between the burning fuel and underlying ashes by the baroclinic instability does not occur. However, the baroclinic instability may have time to operate within the differentially rotating burning layer, potentially bringing it into rigid rotation.Comment: To appear in The Astrophysical Journal; minor corrections made to tables and figure

In vitro susceptibility of Clostridium difficile to SMT19969 and comparators, as well as the killing kinetics and post-antibiotic effects of SMT19969 and comparators against C. difficile

© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/ 4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.OBJECTIVES: SMT19969 is a novel antimicrobial under clinical development for the treatment of Clostridium difficile infection (CDI). The objective was to determine the comparative susceptibility of 82 C. difficile clinical isolates (which included ribotype 027 isolates and isolates with reduced metronidazole susceptibility) to SMT19969, fidaxomicin, vancomycin and metronidazole and to determine the killing kinetics and post-antibiotic effects of SMT19969, fidaxomicin and vancomycin against C. difficile. METHODS: MICs were determined by agar incorporation. Killing kinetics and post-antibiotic effects were determined against C. difficile BI1, 630 and 5325 (ribotypes 027, 012 and 078, respectively). RESULTS: SMT19969 showed potent inhibition of C. difficile (MIC90=0.125 mg/L) and was markedly more active than either metronidazole (MIC90 = 8 mg/L) or vancomycin (MIC90 = 2 mg/L). There were no differences in susceptibility to SMT19969 between different ribotypes. Fidaxomicin was typically one doubling dilution more active than SMT19969 and both agents maintained activity against isolates with reduced susceptibility to metronidazole. In addition, SMT19969 was bactericidal against the C. difficile strains tested, with reductions in viable counts to below the limit of detection by 24 h post-inoculation. Vancomycin was bacteriostatic against all three strains. Fidaxomicin was bactericidal although reduced killing was observed at concentrations <20 × MIC against C. difficile BI1 (ribotype 027) compared with other strains tested. CONCLUSIONS: These data demonstrate that SMT19969 is associated with potent and bactericidal activity against the strains tested and support further investigation of SMT19969 as potential therapy for CDI.Peer reviewedFinal Published versio

Randomized trials, generalizability, and meta-analysis: Graphical insights for binary outcomes

BACKGROUND: Randomized trials stochastically answer the question. "What would be the effect of treatment on outcome if one turned back the clock and switched treatments in the given population?" Generalizations to other subjects are reliable only if the particular trial is performed on a random sample of the target population. By considering an unobserved binary variable, we graphically investigate how randomized trials can also stochastically answer the question, "What would be the effect of treatment on outcome in a population with a possibly different distribution of an unobserved binary baseline variable that does not interact with treatment in its effect on outcome?" METHOD: For three different outcome measures, absolute difference (DIF), relative risk (RR), and odds ratio (OR), we constructed a modified BK-Plot under the assumption that treatment has the same effect on outcome if either all or no subjects had a given level of the unobserved binary variable. (A BK-Plot shows the effect of an unobserved binary covariate on a binary outcome in two treatment groups; it was originally developed to explain Simpsons's paradox.) RESULTS: For DIF and RR, but not OR, the BK-Plot shows that the estimated treatment effect is invariant to the fraction of subjects with an unobserved binary variable at a given level. CONCLUSION: The BK-Plot provides a simple method to understand generalizability in randomized trials. Meta-analyses of randomized trials with a binary outcome that are based on DIF or RR, but not OR, will avoid bias from an unobserved covariate that does not interact with treatment in its effect on outcome