In Vitro Susceptibility of Fusarium to Isavuconazole.

To evaluate the in vitro susceptibility of Fusarium to isavuconazole, 75 clinical isolates were identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry and then tested with a broth microdilution method (EUCAST) and the gradient concentration strip (GCS) technique. The activity of isavuconazole overall was shown to be limited, with an MIC50 of >16 µg/ml, without significant differences between the species complexes. The categorical agreement between GCS and EUCAST was 97.4% to 100%, making the GCS as a valuable alternative.

Comparison of the MICs Obtained by Gradient Concentration Strip and EUCAST Methods for Four Azole Drugs and Amphotericin B against Azole-Susceptible and -Resistant Aspergillus Section Fumigati Clinical Isolates.

Reference methods used to assess the drug susceptibilities of Aspergillus fumigatus isolates consisted of EUCAST and CLSI standardized broth microdilution techniques. Considering the increasing rate and the potential impact on the clinical outcome of azole resistance in A. fumigatus, more suitable techniques for routine testing are needed. The gradient concentration strip (GCS) method has been favorably evaluated for yeast testing. The aim of this study was to compare the CGS test with EUCAST broth microdilution for amphotericin B (AMB), posaconazole (PCZ), itraconazole (ITZ), voriconazole (VRZ), and isavuconazole (ISA). A total of 121 Aspergillus section Fumigati strains were collected, including 24 A. fumigatus sensu stricto strains that were resistant to at least one azole drug. MICs were determined using GCS and EUCAST methods. Essential agreement between the 2 methods was considered when MICs fell within ±1 dilution or ±2 dilutions of the 2-fold dilution scale. Categorical agreement was defined as the percentage of strains classified in the same category (susceptible, intermediate, or resistant) with both methods. Essential agreements with ±1 dilution and ±2 dilutions were 96.7, 93.4, 90.0, 89.3, and 95% and 100, 99.2, 100, 97.5, and 100% for AMB, PCZ, ITZ, VRZ, and ISA, respectively. Categorical agreements were 94.3, 86.1, 89.3, and 88.5% for AMB, PCZ, ITZ, and VRZ, respectively. Detection of resistance was missed with the GCS for one strain (4.1%) for PCZ and for 2 strains (8.3%) for ISA. Determination of ITZ MICs using the GCS allowed the detection of 91.7% of azole-resistant strains. The GCS test appears to be a valuable method for screening azole-resistant A. fumigatus clinical isolates.

Spin Flips versus Spin Transport in Nonthermal Electrons Excited by Ultrashort Optical Pulses in Transition Metals.

A joint theoretical and experimental investigation is performed to understand the underlying physics of laser-induced demagnetization in Ni and Co films with varying thicknesses excited by 10 fs optical pulses. Experimentally, the dynamics of spins is studied by determining the time-dependent amplitude of the Voigt vector, retrieved from a full set of magnetic and nonmagnetic quantities performed on both sides of films, with absolute time reference. Theoretically, ab initio calculations are performed using time-dependent density functional theory. Overall, we demonstrate that spin-orbit induced spin flips are the most significant contributors with superdiffusive spin transport, which assumes only that the transport of majority spins without spin flips induced by scattering does not apply in Ni. In Co it plays a significant role during the first ∼20 fs only. Our study highlights the material dependent nature of the demagnetization during the process of thermalization of nonequilibrium spins.

Transcriptomic Signature of the CD24hi CD38hi Transitional B Cells Associated With an Immunoregulatory Phenotype in Renal Transplant Recipients.

The role of B cells after transplant regarding allograft rejection or tolerance has become a topic of major interest. Recently, in renal transplant recipients, a B cell signature characterized by the overexpression of CD19+ CD38hi CD24hi transitional B cells has been observed in operationally tolerant patients and in belatacept-treated patients with significantly lower incidence of donor-specific antibodies. The phenotypic and functional characterization of these transitional B cells is far from exhaustive. We present the first transcriptomic and phenotypic analysis associated with this cell phenotype. Three populations were studied and compared: (i) transitional CD24hi CD38hi , (ii) CD24+ CD38- , and (iii) CD24int CD38int B cells. Transcriptome bioinformatic analysis revealed a particular signature for the CD24hi CD38hi population. Phenotypic analysis showed that CD24hi CD38hi transitional B cells also expressed CD9, CD10, CD1b and inducible T cell costimulator ligand (ICOS-L) markers. In addition, we found enrichment of IL-10+ cells among CD24hi CD38hi cells expressing ICOS-L and CD1b, the latter showing regulatory properties. Renal transplant recipients treated with belatacept exhibited significant expression of CD1b. Our results show that transitional CD24hi CD38hi B cells exhibit a distinct and specific profile, and this could be helpful for understanding of immune-regulatory mechanisms and immune monitoring in the field of organ transplant and autoimmune disease.

Distinguishing the ultrafast dynamics of spin and orbital moments in solids.

For an isolated quantum particle, such as an electron, the orbital (L) and spin (S) magnetic moments can change provided that the total angular momentum of the particle is conserved. In condensed matter, an efficient transfer between L and S can occur owing to the spin-orbit interaction, which originates in the relativistic motion of electrons. Disentangling the absolute contributions of the orbital and spin angular momenta is challenging, however, as any transfer between the two occurs on femtosecond timescales. Here we investigate such phenomena by using ultrashort optical laser pulses to change the magnetization of a ferromagnetic film and then probe its dynamics with circularly polarized femtosecond X-ray pulses. Our measurements enable us to disentangle the spin and orbital components of the magnetic moment, revealing different dynamics for L and S. We highlight the important role played by the spin-orbit interaction in the ultrafast laser-induced demagnetization of ferromagnetic films, and show also that the magneto-crystalline anisotropy energy is an important quantity to consider in such processes. Our study provides insights into the dynamics in magnetic systems as well as perspectives for the ultrafast control of information in magnetic recording media.

The contribution of fetal MR imaging to the assessment of oesophageal atresia.

OBJECTIVE: Present challenges are to improve the diagnosis rate of oesophageal atresia (OA) and evaluate as completely as possible a fetus affected by OA, specifically the type of OA and the length of the gap. Our aim was to evaluate the accuracy of fetal MR imaging (fMRI) for diagnosis of OA. METHODS: We reviewed fMRI performed because of sonographic suspicion of an OA. The signs reviewed included stomach size, "pouch sign", bowing of the trachea and visualization of the lower oesophageal lumen. The fetuses were assigned by consensus as having or not having EA, as well as having a tracheaoesophageal fistula (TOF). All findings were correlated with postnatal data. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS: Se, Sp, PPV and NPV of the technique were respectively 91%, 100%, 100% and 88%. The presence of the pouch sign yielded corresponding values of 82%, 100%, 100% and 78%. Mid-tracheal bowing was correlated positively with EA. The type of atresia was correctly evaluated in 90% of patients. CONCLUSION: fMRI is useful for the diagnosis of EA through the visualization of the oesophageal pouch or through associated signs such as tracheal bowing. Visualization of the lower oesophageal lumen seems to be a good sign of TEF. KEY POINTS: • Challenges are to improve the prenatal diagnosis of EA and associated malformations. • fMRI is able to diagnose EA through demonstration of the pouch sign. • Tracheal bowing is a promising indirect sign of EA. • Tracheoesophageal fistula can also be suspected thanks to fMRI. • Obstetrical US, fMRI and fetal CT are complementary for assessing associated malformations.

How to improve the preoperative staging of presumed early-stage endometrioid endometrial cancer?

PURPOSE OF INVESTIGATION: Accurate preoperative staging of early-stage endometrioid endometrial cancer (EEC) is necessary to avoid under or over surgical treatment. The objective is to determine the rate of understaging and to evaluate the accuracy of different methods: hysteroscopy-curettage versus endometrial biopsy in predicting the final stage. MATERIALS AND METHODS: This retrospective single-centre study led from 2000 to 2010, included women with EEC preoperatively assessed at low- or intermediate-risk. Understaging was defined as a postoperative FIGO Stage > 1 or a determination of high risk after the final histopathologic diagnosis. RESULTS: The study included 101 women (75 low-risk and 26 intermediate-risk). Final diagnosis was upstaged for 26 of them, more frequently in the presumed intermediate-risk group (57.7% vs 14.7%, p < 0.001). The rate of preoperative understaging was higher in the women with endometrial biopsies than those with curettage (34.5% vs 15.2%, p = 0.04). CONCLUSIONS: Hysteroscopy-curettage combined with magnetic resonance imaging (MRI) may improve preoperative staging of early-stage EEC, especially for presumed intermediate-risk disease.

Kidney transplant recipients treated with belatacept exhibit increased naïve and transitional B cells.

Phase III clinical studies have shown that kidney transplant (KT) recipients treated with the costimulation blocker belatacept exhibited a better renal allograft function and lower donor-specific anti-HLA immunization when compared to recipients treated with calcineurin inhibitors (CNI). We analyzed B cell phenotype in KT recipients treated with belatacept and stable renal function (N = 13). Results were compared to those observed in stable patients treated with CNI (N = 12), or with chronic antibody-mediated rejection (N = 5). Both transcriptional profile and phenotypic characterization of peripheral B cells were performed by real-time polymerase chain reaction and flow cytometry, respectively. In belatacept group, the frequency and absolute number of transitional B cells as defined by both phenotypes: CD19(+) CD24(hi) CD38(hi) and CD19(+) IgD(hi) CD38(hi) CD27(-) , as well as naïve B cells were significantly higher compared with CNI group. B cell activating factor (BAFF) and BAFF receptor mRNA levels were significantly lower in belatacept group than in CNI group. These results show for the first time that belatacept influences B cell compartment by favoring the occurrence of transitional B cells with potential regulatory properties, as described in operational tolerant patients. This role may explain the lower alloimmunization rate observed in belatacept-treated patients.

Does a combination of ultrasound, MRI, and biochemical amniotic fluid analysis improve prenatal diagnosis of esophageal atresia?

OBJECTIVE: Prenatal diagnosis of esophageal atresia (EA) remains a challenge. Our objective was to evaluate the combination of sonography, magnetic resonance imaging (MRI), and amniotic fluid biochemical markers in prenatal diagnosis of EA. STUDY DESIGN: A retrospective study of all cases with prenatal suspicion of EA from January 2008 to May 2013 in our regional reference center was carried out. Patients were included if all the three tests were performed. For each test, sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) were evaluated. Each test was compared using Fisher's exact test. RESULTS: Fifteen patients were referred at a median gestational age of 28(+5) weeks (24-36) for suspicion of EA on the basis of small or non-visualized fetal stomach bubble and/or polyhydramnios. Se, Sp, PPV, and NPV for sonographic pouch sign/MRI/biochemical amniotic fluid were respectively 40/100/100/45.5%, 80/100/100/71.4%, and 90/60/81.8/75%. MRI was the best predictive test (p = 0.007). CONCLUSION: In case of ultrasound prenatal suspicion of EA (with or without visualization of the pouch sign), an MRI at 30-32 weeks using fast imaging employing steady-state acquisition should be proposed. Biochemical amniotic fluid may be helpful and should be evaluated in a larger study.

[Antimicrobial peptides: A new alternative for the treatment of aspergillosis]. / Peptides antimicrobiens : une nouvelle alternative pour le traitement des aspergilloses.

Aspergillus fumigatus is the predominant fungal species causing pulmonary aspergillosis. The present-day anti-aspergillosis arsenal is limited, with a number of molecules occasioning severe side effects (amphotericin B) or provoking significant drug interactions (azole derivatives). Moreover, the recent emergence of azole-resistant A. fumigatus strains is a cause for concern. In this context, antimicrobial peptides (AMPs) are emerging as a promising therapeutic approach and alternative or complement to conventional antifungals.

Exciton diffusion in near-infrared absorbing solution-processed organic thin films.

We report on singlet-singlet annihilation and exciton diffusion in as-prepared p-type and annealed n-type thin films of the low-bandgap quinoidal quaterthiophene [QQT(CN)4] using ultrafast transient absorption measurements. The decay dynamics of exciton populations are well described by a one-dimensional diffusion-limited bimolecular recombination, indicating that the singlet excitons migrate preferentially along the stacking direction. Our results show that the exciton diffusion constants in QQT(CN)4 films do not vary significantly upon thermal annealing. Exciton diffusion lengths are measured to be as high as 4 and 5 nm in as-prepared and annealed QQT(CN)4 films, respectively. We also observe an influence of the excitation densities on the singlet exciton diffusion, which is attributed to phonon scattering. Because of the possibility of patterning p-n regions in QQT(CN)4 films by thermal nanolithography techniques, this study provides important insight not only into the photophysical properties of quinoidal oligothiophene derivatives but also for their future integration into high-performance p-n nanostructured near infrared light-sensing devices.

Machine learning to improve the interpretation of intercalating dye-based quantitative PCR results.

This study aimed to evaluate the contribution of Machine Learning (ML) approach in the interpretation of intercalating dye-based quantitative PCR (IDqPCR) signals applied to the diagnosis of mucormycosis. The ML-based classification approach was applied to 734 results of IDqPCR categorized as positive (n = 74) or negative (n = 660) for mucormycosis after combining "visual reading" of the amplification and denaturation curves with clinical, radiological and microbiological criteria. Fourteen features were calculated to characterize the curves and injected in several pipelines including four ML-algorithms. An initial subset (n = 345) was used for the conception of classifiers. The classifier predictions were combined with majority voting to estimate performances of 48 meta-classifiers on an external dataset (n = 389). The visual reading returned 57 (7.7%), 568 (77.4%) and 109 (14.8%) positive, negative and doubtful results respectively. The Kappa coefficients of all the meta-classifiers were greater than 0.83 for the classification of IDqPCR results on the external dataset. Among these meta-classifiers, 6 exhibited Kappa coefficients at 1. The proposed ML-based approach allows a rigorous interpretation of IDqPCR curves, making the diagnosis of mucormycosis available for non-specialists in molecular diagnosis. A free online application was developed to classify IDqPCR from the raw data of the thermal cycler output ( http://gepamy-sat.asso.st/ ).

Femtosecond spectroscopy probes the folding quality of antibody fragments expressed as GFP fusions in the cytoplasm.

Time-resolved femtosecond spectroscopy can improve the application of green fluorescent proteins (GFPs) as protein-folding reporters. The study of ultrafast excited-state dynamics (ESD) of GFP fused to single chain variable fragment (scFv) antibody fragments, allowed us to define and measure an empirical parameter that only depends on the folding quality (FQ) of the fusion. This method has been applied to the analysis of genetic fusions expressed in the bacterial cytoplasm and allowed us to distinguish folded and thus functional antibody fragments (high FQ) with respect to misfolded antibody fragments. Moreover, these findings were strongly correlated to the behavior of the same scFvs expressed in animal cells. This method is based on the sensitivity of the ESD to the modifications in the tertiary structure of the GFP induced by the aggregation state of the fusion partner. This approach may be applicable to the study of the FQ of polypeptides over-expressed under reducing conditions.

Surface plasmon dynamics in arrays of subwavelength holes: the role of optical interband transitions.

Using femtosecond optical spectroscopy, we study the ultrafast dynamics of the surface plasmon polaritons in gold arrays of subwavelength holes. A large time dependent spectral broadening and shift of the surface plasmon resonances are reported. The experimental results are modeled by the diffraction of a transverse electromagnetic field through the nanostructure, taking into account both the electron dynamics near the interband transitions and the Drude-like conductivity of the metal. Our analysis, using either a theoretical or an experimentally determined dielectric function of gold, suggests that the losses propagation in plasmonic devices is strongly influenced by intrinsic and extrinsic electron scattering mechanisms.

The neuropeptide pituitary adenylate cyclase-activating polypeptide exerts anti-apoptotic and differentiating effects during neurogenesis: focus on cerebellar granule neurones and embryonic stem cells.

Pituitary adenylate cyclase-activating polypeptide (PACAP) was originally isolated from ovine hypothalamus on the basis of its hypophysiotrophic activity. It has subsequently been shown that PACAP and its receptors are widely distributed in the central nervous system of adult mammals, indicating that PACAP may act as a neurotransmitter and/or neuromodulator. It has also been found that PACAP and its receptors are expressed in germinative neuroepithelia, suggesting that PACAP could be involved in neurogenesis. There is now compelling evidence that PACAP exerts neurotrophic activities in the developing cerebellum and in embryonic stem (ES) cells. In particular, the presence of PACAP receptors has been demonstrated in the granule layer of the immature cerebellar cortex, and PACAP has been shown to promote survival, inhibit migration and activate neurite outgrowth of granule cell precursors. In cerebellar neuroblasts, PACAP is a potent inhibitor of the mitochondrial apoptotic pathway through activation of the MAPkinase extracellular regulated kinase. ES cells and embryoid bodies (EB) also express PACAP receptors and PACAP facilitates neuronal orientation and induces the appearance of an electrophysiological activity. Taken together, the anti-apoptotic and pro-differentiating effects of PACAP characterised in cerebellar neuroblasts as well as ES and EB cells indicate that PACAP acts not only as a neurohormone and a neurotransmitter, but also as a growth factor.

[Etiological orientation from the analysis morphological and constitutional of urinary stones in Conakry]. / Orientation etiologique a partir de l'analyse morphologique et constitutionnelle des lithiases urinaires a Conakry.

INTRODUCTION: The epidemiological profile of urinary stones varies from region of the world to another according to food habit and certain enviromental factors. The aim of our study was to establish an etiological approach of the urinary lithiasis collected in Conakry by morphological and constitutional analysis. MATERIALS AND METHODS: It was a prospective study from january 1 rst 2003 to january 1 rst 2004 concerning all the stones collected. They were analysed by binocular magnifying glass and infra red spectrophotometry of Fourier. RESULTS: During the period, 18 patients were observed (14 male, 4 femele) of 27.4 +/- 4 years old (from 2 to 69) living mainly in urban environment. From these patients 28 stones were collected; 12 spontaneously and 16 surgicaly. Their composition were whewellite (36%), struvite (29%), carbapatite (14%), urates (14%) and weddellite (7%). In Conakry stones come mainly from hyperoxaluria and urinary tract infection; hypercalciuria is uncomon. CONCLUSION: The urinary calculations examined among patients show in the adult a prevalence of elements in favour of a hyperoxalurie and a notable context of urinary infections in particular in the child; the pure hypercalciurie remains negligible in Conakry, we plan to lead a thorough work to the national scales.

Optical response of periodically modulated nanostructures near the interband transition threshold of noble metals.

We investigate the influence of the core d-electrons on the spectral optical response of arrays of sub-wavelength holes near the transition from the d-band to the Fermi level of noble metals (d?E(F)). Our model shows that, due to the dispersion of the metal dielectric function near d?E(F), the first order peaks in the enhanced spectral transmission shift nonlinearly as a function of the period of the nanostructure. In addition, we outline in that spectral region an apparent large resonance which does not depend on the geometrical parameters of the nanostructure. It is shown to correspond to the transparency window resulting from the spectral superposition of the large absorption associated to the core d-electrons and high reflectivity due to the conduction electrons. The analysis is performed for gold, copper and silver nanostructures.

[Endovascular stent grafting for chronic proximal thoracic aortic pseudoaneurysm]. / Faux anévrysme chronique de l'aorte thoracique descendante proximale: traitement endovasculaire percutané.

Chronic descending aortic pseudoaneurysm generally result from traumatic and can spontaneously progress to rupture. We report the case of a 70-year-old patient presenting a chronic pseudoaneurysm of the thoracic aorta treated by endovascular stent-grafting. The patient underwent imaging evaluation for endoluminal repair: thoracic aorta was evaluated by contrast-enhanced CT scan and supra-aortic and iliac vessels were evaluated by MRI-imaging. Stent-graft was deployed under fluoroscopic guidance across the aneurysmal defect. The left sub-clavian artery was covered, but no ischemic symptoms appeared and transposition of the left sub-clavian artery was not necessary. Clinical and radiological follow-up at 6 and 30 months showed total exclusion and thrombosis of the pseudoaneurysm. Chronic pseudoaneurysm of the thoracic aorta do benefit from endoluminal repair, which is adapted to patients with high surgical risk.

Deep infiltrating endometriosis: Should rectal and vaginal opacification be systematically used in MR imaging?

OBJECTIVES: To evaluate the interest of rectal and vaginal filling in vaginal and recto-sigmoid endometriosis with MR imaging. To compare the results between a senior and a junior radiologist review. METHODS: Sixty-seven patients with clinically suspected deep infiltrating endometriosis were included in our MRI protocol consisting of repeated T2-weigthed sequences (axial and sagittal) before and after rectal and vaginal marking with ultrasonography gel. Vaginal and recto-sigmoid endometriosis lesions were analyzed before and after opacification. The inter-reader agreement between senior and junior scores was studied. RESULTS: Concerning vaginal and muscularis and beyond colonic involvement, no significant difference (P=0.32) was observed and the inter-reader agreement was excellent (K=0.96 and 0.97 respectively). Concerning serosa colonic lesions, a significant difference was observed (P=0.01) and the inter-reader agreement was poor (K=0). CONCLUSIONS: Rectal and vaginal filling in endometriosis staging with MRI is not necessary no matter the reader experiment.

Directly probing spin dynamics in a molecular magnet with femtosecond time-resolution.

We show that a vanadium-chromium Prussian blue analogue, which is a room-temperature molecule-based magnet, displays a fast magnetic response on a femtosecond timescale that is attributed to the super-exchange interaction between the metal ions. These dynamics are obtained from femtosecond Faraday magneto-optical (MO) measurements, performed at 50 and 300 K. Exciting at the ligand-to-metal charge-transfer (LMCT) band results in the formation of the 2E excited state on the Cr ion via intersystem crossing (ISC) from the 4LMCT state in less than 250 fs. Subsequent vibrational relaxation in the 2E state occurs on a 0.78 ± 0.05 ps timescale at 50 K and 1.1 ± 0.1 ps at 300 K. The MO measurements can detect the formation of the 2E state on the Cr ion from the change in the super-exchange interaction taking place as a result of the corresponding spin flip associated with the formation of the 2E state. These results open up a new avenue to study molecular magnets using a powerful method that is capable of directly probing spin dynamics on a sub-picosecond timescale in thin film environments.