Interhuman transmission as a potential key parameter for geographical variation in the prevalence of Pneumocystis jirovecii dihydropteroate synthase mutations.

BACKGROUND: Pneumocystis jirovecii dihydropteroate synthase (DHPS) mutations are associated with failure of prophylaxis with sulfa drugs. This retrospective study sought to better understand the geographical variation in the prevalence of these mutations. METHODS: DHPS polymorphisms in 394 clinical specimens from immunosuppressed patients who received a diagnosis of P. jirovecii pneumonia and who were hospitalized in 3 European cities were examined using polymerase chain reaction (PCR) single-strand conformation polymorphism. Demographic and clinical characteristics were obtained from patients' medical charts. RESULTS: Of the 394 patients, 79 (20%) were infected with a P. jirovecii strain harboring one or both of the previously reported DHPS mutations. The prevalence of DHPS mutations was significantly higher in Lyon than in Switzerland (33.0% vs 7.5%; P < .001). The proportion of patients with no evidence of sulfa exposure who harbored a mutant P. jirovecii DHPS genotype was significantly higher in Lyon than in Switzerland (29.7% vs 3.0%; P < .001). During the study period in Lyon, in contrast to the Swiss hospitals, measures to prevent dissemination of P. jirovecii from patients with P. jirovecii pneumonia were generally not implemented, and most patients received suboptimal prophylaxis, the failure of which was strictly associated with mutated P. jirovecii. Thus, nosocomial interhuman transmission of mutated strains directly or indirectly from other individuals in whom selection of mutants occurred may explain the high proportion of mutations without sulfa exposure in Lyon. CONCLUSIONS: Interhuman transmission of P. jirovecii, rather than selection pressure by sulfa prophylaxis, may play a predominant role in the geographical variation in the prevalence in the P. jirovecii DHPS mutations.

Detection of Optimal Models in Parameter Space with Support Vector Machines

The paper proposes an approach aimed at detecting optimal model parameter combinations to achieve the most representative description of uncertainty in the model performance. A classification problem is posed to find the regions of good fitting models according to the values of a cost function. Support Vector Machine (SVM) classification in the parameter space is applied to decide if a forward model simulation is to be computed for a particular generated model. SVM is particularly designed to tackle classification problems in high-dimensional space in a non-parametric and non-linear way. SVM decision boundaries determine the regions that are subject to the largest uncertainty in the cost function classification, and, therefore, provide guidelines for further iterative exploration of the model space. The proposed approach is illustrated by a synthetic example of fluid flow through porous media, which features highly variable response due to the parameter values' combination.

Exact representation of antenna system diversity performance from input parameter description

A simplc formulation Io compute thc envelope correlation of anantenna divemiry system is dcrired. 11 is shown how to compute theenvelope correlation hom the S-parameter descnplian of the antennasystem. This approach has the advantage that i t does not require thecomputation nor the measurement of the radiation panem of theantenna system. It also offers the advantage of providing a clcaunderstanding ofthe effects ofmutual coupling and input match on thediversity performance of the antcnnii system.

CD34/QBEND10 immunostaining in bone marrow biopsies: an additional parameter for the diagnosis and classification of myelodysplastic syndromes.

CD34/QBEND10 immunostaining has been assessed in 150 bone marrow biopsies (BMB) including 91 myelodysplastic syndromes (MDS), 16 MDS-related AML, 25 reactive BMB, and 18 cases where RA could neither be established nor ruled out. All cases were reviewed and classified according to the clinical and morphological FAB criteria. The percentage of CD34-positive (CD34 +) hematopoietic cells and the number of clusters of CD34+ cells in 10 HPF were determined. In most cases the CD34+ cell count was similar to the blast percentage determined morphologically. In RA, however, not only typical blasts but also less immature hemopoietic cells lying morphologically between blasts and promyelocytes were stained with CD34. The CD34+ cell count and cluster values were significantly higher in RA than in BMB with reactive changes (p&lt;0.0001 for both), in RAEB than in RA (p=0.0006 and p=0.0189, respectively), in RAEBt than in RAEB (p=0.0001 and p=0.0038), and in MDS-AML than in RAEBt (p&lt;0.0001 and p=0.0007). Presence of CD34+ cell clusters in RA correlated with increased risk of progression of the disease. We conclude that CD34 immunostaining in BMB is a useful tool for distinguishing RA from other anemias, assessing blast percentage in MDS cases, classifying them according to FAB, and following their evolution.

Regional specificity of MRI contrast parameter changes in normal ageing revealed by voxel-based quantification (VBQ).

Normal ageing is associated with characteristic changes in brain microstructure. Although in vivo neuroimaging captures spatial and temporal patterns of age-related changes of anatomy at the macroscopic scale, our knowledge of the underlying (patho)physiological processes at cellular and molecular levels is still limited. The aim of this study is to explore brain tissue properties in normal ageing using quantitative magnetic resonance imaging (MRI) alongside conventional morphological assessment. Using a whole-brain approach in a cohort of 26 adults, aged 18-85years, we performed voxel-based morphometric (VBM) analysis and voxel-based quantification (VBQ) of diffusion tensor, magnetization transfer (MT), R1, and R2* relaxation parameters. We found age-related reductions in cortical and subcortical grey matter volume paralleled by changes in fractional anisotropy (FA), mean diffusivity (MD), MT and R2*. The latter were regionally specific depending on their differential sensitivity to microscopic tissue properties. VBQ of white matter revealed distinct anatomical patterns of age-related change in microstructure. Widespread and profound reduction in MT contrasted with local FA decreases paralleled by MD increases. R1 reductions and R2* increases were observed to a smaller extent in overlapping occipito-parietal white matter regions. We interpret our findings, based on current biophysical models, as a fingerprint of age-dependent brain atrophy and underlying microstructural changes in myelin, iron deposits and water. The VBQ approach we present allows for systematic unbiased exploration of the interaction between imaging parameters and extends current methods for detection of neurodegenerative processes in the brain. The demonstrated parameter-specific distribution patterns offer insights into age-related brain structure changes in vivo and provide essential baseline data for studying disease against a background of healthy ageing.

The vasodilatory response of skin microcirculation to local heating is subject to desensitization

RAPPORT DE SYNTHESE Introduction : dans la présente étude, nous nous sommes intéressés à la vasodilatation cutanée induite par le réchauffement local (hyperémie thermique). Il est établi, qu'une partie de cette réponse vasculaire est médiée par l'oxyde nitrique (NO). De manière générale, les effets du NO peuvent être sujets à une désensibilisation, comme nous le démontre le phénomène bien connu de tolérance aux dérivés nitrés. Le but du présent travail était d'évaluer si une telle désensibilisation existe dans le cas de l'hyperémie thermique. Méthodes : nous avons donc examiné si une première stimulation thermique pouvait en atténuer une deuxième, induite plus tard sur le même site cutané à une intervalle de 2h ou 4h. Pour vérifier directement l'effet du réchauffement local sur la sensibilité de la microcirculation cutanée au NO, nous avons de plus appliqué un donneur de NO (nitroprussiate de sodium, SNP) par la technique d' iontophorèse, sur des sites cutanés préalablement soumis à un échauffement local 2h ou 4h auparavant. Nous avons examinés 12 sujets en bonne santé habituelle, de sexe masculin, non fumeurs, âgés de 18 à 30 ans, ne prenant aucune médication. Le flux sanguin dermique a été mesuré par imagerie laser Doppler (LDI, Moor Instruments) sur la face antérieur de l'avant-bras. Le réchauffement local de la peau a été effectué grâce a des petits anneaux métalliques thermo-contrôlés contenant de l'eau. La température était initialement de 34°C. Elle a été augmentée à 41 °C en une minute et maintenue à cette valeur durant 30 minutes. Cette manoeuvre a été répétée sur le même site cutané soit 2 h, soit 4h plus tard. Quant à l'iontophorèse de SNP, elle a été effectuée sur des sites ayant préalablement subi, 2h ou 4h auparavant, un échauffement unique appliqué selon la technique qui vient d'être décrite. Résultats : nous avons observé une atténuation de l'hyperémie thermique lorsque celleci était examinée 2h après un premier échauffement local. Lorsque l'intervalle était de 4h la réponse vasodilatatrice n'était pas réduite. Nous avons également observé une atténuation de la réponse vasodilatatrice au SNP lorsque celui-ci a était appliqué 2h, mais non 4h après un premier échauffement local. Conclusion :cette étude démontre que la réponse vasodilatatrice cutanée induite par l'échauffement local est bien sujette à désensibilisation, comme nous en avions formulé l'hypothèse. Ce phénomène est transitoire. Il est lié, au moins en partie, à une baisse de sensibilité de la microcirculation cutanée aux effets vasodilatateurs du NO.

Linear least squares estimation of the first order moving average parameter

We propose an iterative procedure to minimize the sum of squares function which avoids the nonlinear nature of estimating the first order moving average parameter and provides a closed form of the estimator. The asymptotic properties of the method are discussed and the consistency of the linear least squares estimator is proved for the invertible case. We perform various Monte Carlo experiments in order to compare the sample properties of the linear least squares estimator with its nonlinear counterpart for the conditional and unconditional cases. Some examples are also discussed

Cooling and heating by adiabatic magnetization in Ni50Mn34In16 magnetic shape-memory alloy

We report on measurements of the adiabatic temperature change in the inverse magnetocaloric Ni50Mn34In16 alloy. It is shown that this alloy heats up with the application of a magnetic field around the Curie point due to the conventional magnetocaloric effect. In contrast, the inverse magnetocaloric effect associated with the martensitic transition results in the unusual decrease of temperature by adiabatic magnetization. We also provide magnetization and specific heat data which enable to compare the measured temperature changes to the values indirectly computed from thermodynamic relationships. Good agreement is obtained for the conventional effect at the second-order paramagnetic-ferromagnetic phase transition. However, at the first-order structural transition the measured values at high fields are lower than the computed ones. Irreversible thermodynamics arguments are given to show that such a discrepancy is due to the irreversibility of the first-order martensitic transition.

The vasodilatory response of skin microcirculation to local heating is subject to desensitization.

BACKGROUND: In humans, local heating increases skin perfusion by mechanisms dependent on nitric oxide (NO). Because the vascular effects of NO may be subject to desensitization, we examined whether a first local thermal stimulus would attenuate the hyperemic response to a second one applied later. METHODS: Twelve healthy young men were studied. Skin blood flow (SkBF) was measured on forearm skin with laser Doppler imaging. Local thermal stimuli (temperature step from 34 to 41 degrees C maintained for 30 minutes) were applied with temperature-controlled chambers. We also tested the influence of prior local heating on the vasodilation induced by sodium nitroprusside (SNP), a donor of NO. RESULTS: On reheating the same spot after two hours, the response of SkBF (i.e., plateau SkBF at 30 minutes minus SkBF at 34 degrees C) was lower than during the first stimulation (mean+/-SD 404+/-212 perfusion units [PU] vs. 635+/-100 PU; P&lt;0.001). There was no such difference when reheating after four hours (654+/-153 vs. 645+/-103 PU; P=NS). Two, but not four, hours after local heating, the response of SkBF to SNP was reduced. CONCLUSION: The NO-dependent hyperemic response induced by local heating in human skin is subject to desensitization. At least one part of the mechanism implicated consists of a desensitization to the effects of NO itself.

Vortices in atomic Bose-Einstein condensates in the large-gas-parameter region

In this work we compare the results of the Gross-Pitaevskii and modified Gross-Pitaevskii equations with ab initio variational Monte Carlo calculations for Bose-Einstein condensates of atoms in axially symmetric traps. We examine both the ground state and excited states having a vortex line along the z axis at high values of the gas parameter and demonstrate an excellent agreement between the modified Gross-Pitaevskii and ab initio Monte Carlo methods, both for the ground and vortex states.

Anomalous crystallization of hydrogenated amorphous silicon during fast heating ramps

Thermal crystallization experiments carried out using calorimetry on several a-Si:H materials with different microstructures are reported. The samples were crystallized during heating ramps at constant heating rates up to 100 K/min. Under these conditions, crystallization takes place above 700 C and progressively deviates from the standard kinetics. In particular, two crystallization processes were detected in conventional a-Si:H, which reveal an enhancement of the crystallization rate. At100 K/min, such enhancement is consistent with a diminution of the crystallization time by a factor of 7. In contrast, no systematic variation of the resulting grain size was observed. Similar behavior was also detected in polymorphous silicon and silicon nanoparticles, thus showing that it is characteristic of a variety of hydrogenated amorphous silicon materials.