Imaging the effect of acoustically induced cavitation bubbles on the generation of shear-waves by ultrasonic radiation force

In soft solids, the acoustic radiation force on bubbles generates a shear wave. This bubble-based shear wave can be imaged using high frame rate ultrasound imaging. We report here an experiment where cavitation is induced in a tissue mimicking material by an ultrasonic tone-burst excitation, which also pushes the bubbles. The generated shear wave was imaged and the energy backscattered by the bubbles measured. The tone burst excitation was iterated at the same location and the decrease of both the amplitude of the particle velocity induced by the shear wave and the backscattered energy was shown. Data treatment to extract the bubbles' contribution to this two quantities, and a simple theoretical model allowed us to point out their linear dependence.http://deepblue.lib.umich.edu/bitstream/2027.42/84304/1/CAV2009-final129.pd

The Conserved nhaAR Operon Is Drastically Divergent between B2 and Non-B2 Escherichia coli and Is Involved in Extra-Intestinal Virulence

The Escherichia coli species is divided in phylogenetic groups that differ in their virulence and commensal distribution. Strains belonging to the B2 group are involved in extra-intestinal pathologies but also appear to be more prevalent as commensals among human occidental populations. To investigate the genetic specificities of B2 sub-group, we used 128 sequenced genomes and identified genes of the core genome that showed marked difference between B2 and non-B2 genomes. We focused on the gene and its surrounding region with the strongest divergence between B2 and non-B2, the antiporter gene nhaA. This gene is part of the nhaAR operon, which is in the core genome but flanked by mobile regions, and is involved in growth at high pH and high sodium concentrations. Consistently, we found that a panel of non-B2 strains grew faster than B2 at high pH and high sodium concentrations. However, we could not identify differences in expression of the nhaAR operon using fluorescence reporter plasmids. Furthermore, the operon deletion had no differential impact between B2 and non-B2 strains, and did not result in a fitness modification in a murine model of gut colonization. Nevertheless, sequence analysis and experiments in a murine model of septicemia revealed that recombination in nhaA among B2 strains was observed in strains with low virulence. Finally, nhaA and nhaAR operon deletions drastically decreased virulence in one B2 strain. This effect of nhaAR deletion appeared to be stronger than deletion of all pathogenicity islands. Thus, a population genetic approach allowed us to identify an operon in the core genome without strong effect in commensalism but with an important role in extra-intestinal virulence, a landmark of the B2 strains

Normal Stresses and Interface Displacement: Influence of Viscoelasticity on Enhanced Oil Recovery Efficiency

International audienceOne of chemical Enhanced Oil Recovery (EOR) methods consists in injecting aqueous solutions of polymers into the reservoir in order to improve mobility ratio between the injected fluid and the remaining oil. This "polymer flooding" process is usually only characterized with the low shear viscosity of the injected fluid, even if these aqueous solutions are strongly shear thinning and may show high elastic properties evidenced by normal stresses appearance. In order to study the mechanisms at the interface level, we develop simple model experimentations with the goal of quantifying the influence of viscoelastic properties on fluid displacement in a simple geometry. For this purpose, we propose and characterize a model fluid formulation, for which elastic and viscous effects can be tuned systematically. We study then the displacement of a viscous oil by a Newtonian non elastic, a viscoelastic or a purely shear thinning fluid in a two dimensional flow cell. Observing the shape of the interface between aqueous fluids and displaced oil permits to appreciate viscoelasticity effects on the displacement. Using model geometries and controlled rheology fluids, we show that viscoelastic fluids tend to better displace immiscible liquids than Newtonian fluids and that those effects are closely related to the apparitions of normal stresses independently of shear thinning property or variation of interfacial tension as soon as viscous effects govern the flow

Enhanced displacement of a liquid pushed by a viscoelastic fluid.

International audienceWe consider the displacement, in a rectangular channel, of a Newtonian oil pushed by different types of liquids (Newtonian, shear-thinning, viscoelastic) of slightly higher apparent viscosity. ln the absence of viscoelastic effects the interface between the two fluids becomes sharper at larger velocities, so that the thickness of the lateral film left behind increases with the flow rate. On the contrary, with a viscoelastic fluid, the shape of the interface is almost independent of the velocity so that the thickness of the lateral film is approximately constant. Moreover this thickness decreases when the ratio of normal to tangential stresses increases, suggesting that this effect can be attributed to normal stress differences. A heuristic theoretical approach tends to confirm this statement

Acoustically induced and controlled micro-cavitation bubbles as active source for transcranial adaptive focusing

The skull bone is a strong aberrating medium for ultrasound in the low MHz range. Brain treatment with High Intensity Focused Ultrasound (HIFU) can however be achieved through the skull by multichannel arrays using an adaptive focusing technique. Time-reversal is a robust adaptive technique for correction of aberrations. It achieves moreover a matched filter and then allows the optimal energy concentration for thermal therapy. Nevertheless, this method requires a reference signal sent by a source embedded in brain tissues. Acoustically generated cavitation bubbles are active acoustic sources which can be remotely generated. Therefore, they are suited for this non-invasive time reversal aberration correction. We report here in vitro experiments where micro-cavitation was induced transcranially in agar gel at targeted positions using a coarse aberration correction either obtained from CT-scan based simulations or conventional steering. The bubbles' ultrasonic signature received by the array were then successfully used to optimally focus at the designated locations.http://deepblue.lib.umich.edu/bitstream/2027.42/84308/1/CAV2009-final134.pd

Modifications of filament spectra by shaped octave-spanning laser pulses

In this paper we examine the spectral changes in a white light laser filament due to different pulse shapes generated by a pulse-shaping setup. We particularly explore how the properties of the filament spectra can be controlled by parametrically tailored white light pulses. The experiments are carried out in a gas cell with up to 9 bars of argon. Plasma generation and self-phase modulation strongly affect the pulse in the spectral and temporal domains. By exploiting these effects we show that the pulse spectrum can be modified in a desired way by either using second-order parametric chirp functions to shift the filament spectrum to higher or lower wavelengths, or by optimizing pulse shapes with a genetic algorithm to generate more complex filament spectra. This paper is an example of the application of complex, parametrically shaped white light pulses

Transfer of recessive skr crossability trait into well-adapted French wheat cultivar Barok through marker-assisted backcrossing method

In order to increase genetic diversity in cereals, interspecific or even intergeneric crosses are worthwhile, especially wheat by rye crosses for triticale production. However, these crosses often fail due to inhibiting genes. To overcome this obstacle, crossability trait, present in a few wheat cultivars, can be transferred into other wheat lines of agronomical interest. Nevertheless, this transfer remains tedious through conventional backcrossing methods because it is a recessive trait, which requires selfing generations and complex evaluation by many crosses. Here, we present a marker-assisted backcrossing method to transfer this trait more quickly and easily. We chose to introduce the recessive crossability skr, located on chromosome 5BS and originating from Asian wheat, into Barok, a non-crossable French wheat cultivar, with good agronomic characteristics. Six molecular markers, close to the Skr locus, were used to check the transfer of the gene at each of the three backcrosses, without selfing generation nor crosses with rye. Finally, we crossed the predicted crossable lines with rye to validate their crossability. We obtained sixteen lines, morphologically similar to Barok, exhibiting high crossability rate (30%). The markers were thus efficient to transfer the skr crossability but they remain too far from the Skr locus to be considered as diagnostic markers. Indeed, genotyping and phenotyping on other wheat cultivars showed some discrepancies. Nevertheless, this opens the way to enhance genetic diversity more easily and to improve traits of agronomic interest in triticale or wheat as well as to study further barriers to intergeneric crosses

Entrance and exit effects for a viscoelastic liquid displacing a simple liquid through a contraction.

International audienceWe studied the displacement of the interface between a viscoelastic fluid pushing a simple liquid through a rectangular contraction by following the front interface deformation in time. The progressive deformation of the interface until apparent stabilization is followed, which makes it possible to identify a transient and a stationary regime. For low Weissenberg number the shape of the interface is essentially similar to that between two simple liquids. For sufficiently large Weissenberg number the shape of the interface is different: it is narrower before the entrance and wider just after the exit. The characteristics of this shape are qualitatively analogous to those of the interface between the vortices and the convected regions for the flow of a single viscoelastic fluid through a contraction- expansion. This suggests that the entrance effect is due to extensional effects and the exit effect is due to normal stress effects

Rifampicin and clarithromycin (extended release) versus rifampicin and streptomycin for limited Buruli ulcer lesions: a randomised, open-label, non-inferiority phase 3 trial.

BACKGROUND: Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans infection that damages the skin and subcutis. It is most prevalent in western and central Africa and Australia. Standard antimicrobial treatment with oral rifampicin 10 mg/kg plus intramuscular streptomycin 15 mg/kg once daily for 8 weeks (RS8) is highly effective, but streptomycin injections are painful and potentially harmful. We aimed to compare the efficacy and tolerability of fully oral rifampicin 10 mg/kg plus clarithromycin 15 mg/kg extended release once daily for 8 weeks (RC8) with that of RS8 for treatment of early Buruli ulcer lesions. METHODS: We did an open-label, non-inferiority, randomised (1:1 with blocks of six), multicentre, phase 3 clinical trial comparing fully oral RC8 with RS8 in patients with early, limited Buruli ulcer lesions. There were four trial sites in hospitals in Ghana (Agogo, Tepa, Nkawie, Dunkwa) and one in Benin (Pobè). Participants were included if they were aged 5 years or older and had typical Buruli ulcer with no more than one lesion (caterories I and II) no larger than 10 cm in diameter. The trial was open label, and neither the investigators who took measurements of the lesions nor the attending doctors were masked to treatment assignment. The primary clinical endpoint was lesion healing (ie, full epithelialisation or stable scar) without recurrence at 52 weeks after start of antimicrobial therapy. The primary endpoint and safety were assessed in the intention-to-treat population. A sample size of 332 participants was calculated to detect inferiority of RC8 by a margin of 12%. This study was registered with ClinicalTrials.gov, NCT01659437. FINDINGS: Between Jan 1, 2013, and Dec 31, 2017, participants were recruited to the trial. We stopped recruitment after 310 participants. Median age of participants was 14 years (IQR 10-29) and 153 (52%) were female. 297 patients had PCR-confirmed Buruli ulcer; 151 (51%) were assigned to RS8 treatment, and 146 (49%) received oral RC8 treatment. In the RS8 group, lesions healed in 144 (95%, 95% CI 91 to 98) of 151 patients, whereas lesions healed in 140 (96%, 91 to 99) of 146 patients in the RC8 group. The difference in proportion, -0·5% (-5·2 to 4·2), was not significantly greater than zero (p=0·59), showing that RC8 treatment is non-inferior to RS8 treatment for lesion healing at 52 weeks. Treatment-related adverse events were recorded in 20 (13%) patients receiving RS8 and in nine (7%) patients receiving RC8. Most adverse events were grade 1-2, but one (1%) patient receiving RS8 developed serious ototoxicity and ended treatment after 6 weeks. No patients needed surgical resection. Four patients (two in each study group) had skin grafts. INTERPRETATION: Fully oral RC8 regimen was non-inferior to RS8 for treatment of early, limited Buruli ulcer and was associated with fewer adverse events. Therefore, we propose that fully oral RC8 should be the preferred therapy for early, limited lesions of Buruli ulcer. FUNDING: WHO with additional support from MAP International, American Leprosy Missions, Fondation Raoul Follereau France, Buruli ulcer Groningen Foundation, Sanofi-Pasteur, and BuruliVac

Diagnosing Clostridioides difficile infections with molecular diagnostics: multicenter evaluation of revogene C. difficile assay

Clostridioides difficile infections are a significant threat to our healthcare system, and rapid and accurate diagnostics are crucial to implement the necessary infection prevention and control measurements. Nucleic acid amplification tests are such reliable diagnostic tools for the detection of toxigenic Clostridioides difficile strains directly from stool specimens. In this multicenter evaluation, we determined the performance of the revogene C. difficile assay. The analysis was conducted on prospective stool specimens collected from six different sites in Europe. The performance of the revogene C. difficile assay was compared to the different routine diagnostic methods and, for a subset of the specimens, against toxigenic culture. In total, 2621 valid stool specimens were tested, and the revogene C. difficile assay displayed a sensitivity/specificity of 97.1% [93.3-99.0] and 98.9% [98.5-99.3] for identification of Clostridioides difficile infection. Discrepancy analysis using additional methods improved this performance to 98.8% [95.8-99.9] and 99.6% [99.2-99.8], respectively. In comparison to toxigenic culture, the revogene C. difficile assay displayed a sensitivity/specificity of 93.0% [86.1-97.1] and 99.5% [98.7-99.9], respectively. These results indicate that the revogene C. difficile assay is a robust and reliable aid in the diagnosis of Clostridioides difficile infections.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.This study was supported by grants from GenePOC, now part of Meridian Biosciences.published version, accepted versio