Background and purpose
Nerve tissue alterations have rarely been quantified in Charcot–Marie–Tooth type 1A (CMT1A) patients. The aim of the present study was to quantitatively assess the magnetic ...resonance imaging (MRI) anomalies of the sciatic and tibial nerves in CMT1A disease using quantitative neurography MRI. It was also intended to seek for correlations with clinical variables.
Methods
Quantitative neurography MRI was used in order to assess differences in nerve volume, proton density and magnetization transfer ratio in the lower limbs of CMT1A patients and healthy controls. Disease severity was evaluated using the Charcot–Marie–Tooth Neuropathy Score version 2, Charcot–Marie–Tooth examination scores and Overall Neuropathy Limitations Scale scores. Electrophysiological measurements were performed in order to assess the compound motor action potential and the Motor Unit Number Index. Clinical impairment was evaluated using muscle strength measurements and Charcot–Marie–Tooth examination scores.
Results
A total of 32 CMT1A patients were enrolled and compared to 13 healthy subjects. The 3D nerve volume, magnetization transfer ratio and proton density were significantly different in CMT1A patients for the whole sciatic and tibial nerve volume. The sciatic nerve volume was significantly correlated with the whole set of clinical scores whereas no correlation was found between the tibial nerve volume and the clinical scores.
Conclusion
Nerve injury could be quantified in vivo using quantitative neurography MRI and the corresponding biomarkers were correlated with clinical disability in CMT1A patients. The sensitivity of the selected metrics will have to be assessed through repeated measurements over time during longitudinal studies to evaluate structural nerve changes under treatment.
Pheochromocytomas (pheos) and paragangliomas (pgls) are rare tumours of the autonomic nervous system, originating from paraganglia, which are dispersed neuroendocrine organs characterized by ...catecholamine and peptide-producing cells derived from the neural crest. Medical textbooks have traditionally suggested that 10% of pheos are heritable. However, the frequency of heritable pheo has been underestimated. Three syndromic conditions-Von Hippel-Lindau (vhl), multiple endocrine neoplasia type 2 (men2), and neurofibromatosis type 1 (nf1)-and three genes-subunits of the succinate dehydrogenase (SDH) complex: SDHB, SDHC, and SDHD-are established causes of hereditary pheo-pgl. In the last few years, four new genes (SDHA, SDHAF2, MAX, and TMEM127) have been found to be associated with predisposition to these tumours. The present review, illustrated by three case reports, gives an update of the genetic basis of pheo-pgl and of the parent-of-origin effect implicated in the transmission of SDHD and SDHAF2. We discuss the referral criteria that should guide the decision to offer genetic testing to affected patients. We also specify the genes that are most likely implicated-based on particular features such as malignancy, bilateralism, or childhood-onset-to help geneticists efficiently order appropriate genetic tests. Finally, we review the screening recommendations for carriers of a pheo-pgl predisposition mutation.
Proximal 16p11.2 microdeletions are recurrent microdeletions with an overall prevalence of 0.03%. In patients with segmentation defects of the vertebra (SDV), a burden of this microdeletion was ...observed with TBX6 as a candidate gene for SDV. In a published cohort of patients with congenital scoliosis (CS), TBX6 haploinsufficiency was compound heterozygous with a common haplotype. Besides, a single three‐generation family with spondylocostal dysostosis (SCD) was reported with a heterozygous stop‐loss of TBX6. These observations questioned both on the inheritance mode and on the variable expressivity associated with TBX6‐associated SDV. Based on a national recruitment of 56 patients with SDV, we describe four patients with variable SDV ranging from CS to SCD associated with biallelic variations of TBX6. Two patients with CS were carrying a proximal 16p11.2 microdeletion associated with the previously reported haplotype. One patient with extensive SDV was carrying a proximal 16p11.2 microdeletion associated with a TBX6 rare missense change. One patient with a clinical diagnosis of SCD was compound heterozygous for two TBX6 rare missense changes. The three rare variants were affecting the chromatin‐binding domain. Our data illustrate the variable expressivity of recessive TBX6 ranging from CS to SCD.
Representation of atmospheric transport is a major source of error in the estimation of greenhouse gas sources and sinks by inverse modelling. Here we assess the impact on trace gas mole fractions of ...the new physical parameterizations recently implemented in the atmospheric global climate model LMDz to improve vertical diffusion, mesoscale mixing by thermal plumes in the planetary boundary layer (PBL), and deep convection in the troposphere. At the same time, the horizontal and vertical resolution of the model used in the inverse system has been increased. The aim of this paper is to evaluate the impact of these developments on the representation of trace gas transport and chemistry, and to anticipate the implications for inversions of greenhouse gas emissions using such an updated model. Comparison of a one-dimensional version of LMDz with large eddy simulations shows that the thermal scheme simulates shallow convective tracer transport in the PBL over land very efficiently, and much better than previous versions of the model. This result is confirmed in three-dimensional simulations, by a much improved reproduction of the radon-222 diurnal cycle. However, the enhanced dynamics of tracer concentrations induces a stronger sensitivity of the new LMDz configuration to external meteorological forcings. At larger scales, the inter-hemispheric exchange is slightly slower when using the new version of the model, bringing them closer to observations. The increase in the vertical resolution (from 19 to 39 layers) significantly improves the representation of stratosphere/troposphere exchange. Furthermore, changes in atmospheric thermodynamic variables, such as temperature, due to changes in the PBL mixing modify chemical reaction rates, which perturb chemical equilibriums of reactive trace gases. One implication of LMDz model developments for future inversions of greenhouse gas emissions is the ability of the updated system to assimilate a larger amount of high-frequency data sampled at high-variability stations. Others implications are discussed at the end of the paper.
Background SDZ ASM 981 is a selective inhibitor of inflammatory cytokines released from T lymphocytes and mast cells, which has been developed for the treatment of inflammatory skin diseases.
...Objectives In the present study, the atrophogenic potential of SDZ ASM 981 1% cream in humans was compared with that of medium and highly potent topical steroids, and vehicle.
Methods Four different preparations, SDZ ASM 981 1% cream, the corresponding vehicle of SDZ ASM 981 1% cream, betamethasone‐17‐valerate 0·1% cream and triamcinolone acetonide 0·1% cream, were applied to the volar aspect of the forearms of 16 healthy volunteers, twice daily, 6 days a week, for 4 weeks. Skin thickness was evaluated by ultrasound examination, clinical signs of atrophy by stereomicroscopy, and epidermal thickness was assessed by histology.
Results Both topical corticosteroids induced a significant reduction in skin thickness, as compared with SDZ ASM 981 1% cream and vehicle, which were shown to be equivalent. The difference in skin thickness (measured by ultrasound examination) between patients treated with SDZ ASM 981 1% cream and those receiving either of the two topical steroids was significant from day 8 onwards. Histological analysis performed at day 29 showed significant epidermal thinning with topical steroids compared with SDZ ASM 981 1% cream or the vehicle.
Conclusion The lack of atrophogenic properties of SDZ ASM 981 1% cream in this short‐term study demonstrates its potential as long‐term treatment for inflammatory skin diseases, thus overcoming a major drawback of topical steroids. This may also be important for the treatment of children, and sensitive areas of skin, such as the face and skin‐folds.
Biofilms are increasingly implicated as playing a major role in waterborne cryptosporidiosis. This review aims to synthesize all currently available data on interactions between
oocysts and biofilms. ...Initially described following a waterborne outbreak, the integration of
oocysts in biofilm has been well demonstrated. Biofilms appear important in the dissemination/protection of oocysts in the environment. Consequently, it has been suggested that substrate-associated biofilms should be systematically considered in oocyst water quality assessment. The influence of physicochemical parameters has been studied on oocyst biofilm retention. Biofilm surface roughness, ionic concentration (especially Ca
), laminar/turbulent flow, shear stress, and electrostatic repulsion forces appear important to consider regarding oocyst release from biofilm. However, data analysis carried out during this review also revealed important gaps in biological interactions within biofilms, offering many perspectives for future work.
A case of daytime development of deep convection over tropical semi‐arid land is used to evaluate the representation of convection in global and regional models. The case is based on observations ...collected during the African Monsoon Multidisciplinary Analysis (AMMA) field campaign and includes two distinct transition phases, from clear sky to shallow cumulus and from cumulus to deep convection. Different types of models, run with identical initial and boundary conditions, are intercompared: a reference large‐eddy simulation (LES), single‐column model (SCM) version of four different Earth system models that participated in the Coupled Model Intercomparison Project 5 exercise, the SCM version of the European Centre for Medium‐range Weather Forecasts operational forecast model, the SCM version of a mesoscale model and a bulk model. Surface fluxes and radiative heating are prescribed preventing any atmosphere–surface and cloud–radiation coupling in order to simplify the analyses so that it focuses only on convective processes. New physics packages are also evaluated within this framework.
As the LES correctly reproduces the observed growth of the boundary layer, the gradual development of shallow clouds, the initiation of deep convection and the development of cold pools, it provides a basis to evaluate in detail the representation of the diurnal cycle of convection by the other models and to test the hypotheses underlying convective parametrizations. Most SCMs have difficulty in representing the timing of convective initiation and rain intensity, although substantial modifications to boundary‐layer and deep‐convection parametrizations lead to improvements. The SCMs also fail to represent the mid‐level troposphere moistening during the shallow convection phase, which we analyse further. Nevertheless, beyond differences in timing of deep convection, the SCM models reproduce the sensitivity to initial and boundary conditions simulated in the LES regarding boundary‐layer characteristics, and often the timing of convection triggering.
La résurgence de la syphilis est constatée depuis le début des années 2000. Nous décrivons rétrospectivement les cas de syphilis hospitalisés au CHU de Nantes entre 2000 et 2010.
Les dossiers étaient ...retenus sur la base des données sérologiques du service de bactériologie et les données du PMSI. Le diagnostic reposait sur la positivité du TPHA et du VDRL.
Le nombre de sérologies positives a été multiplié par 8 sur la période examinée. Sur les 36 patients hospitalisés, 97 % étaient des hommes, de 17 à 75 ans. Dix-huit étaient infectés par le VIH. Parmi eux, 94 % étaient homosexuels et 67 % avaient un antécédent d’infections sexuellement transmissibles. Le délai moyen entre les symptômes et le diagnostic était significativement plus grand chez les patients non infectés par le VIH. Trente-trois pour cent des patients présentaient une syphilis secondaire cutanéo-muqueuse souvent accompagnée de signes généraux, 50 % une neurosyphilis sous la forme d’une uvéite le plus souvent, et un patient présentait une syphilis tertiaire sous la forme de gommes osseuses. Les patients présentant une syphilis secondaire isolée étaient traités par une à trois injections de benzathine pénicilline G. Les patients présentant une syphilis tardive ou une neurosyphilis étaient traités par pénicilline G ou ceftriaxone. Trente-neuf pour cent des patients atteints de neurosyphilis gardaient des séquelles neurosensorielles.
Ce travail souligne l’augmentation d’incidence de la syphilis en France et les potentielles sévérités et complexités diagnostiques de cette infection, imposant la réalisation plus large de la sérologie de la syphilis devant un tableau clinique compatible.
Syphilis infection increase has been observed since the early 2000s. The medical records of patients hospitalized for syphilis at the tertiary care hospital of Nantes between 2000 and 2010 were retrospectively reviewed.
Cases were selected on the basis of serological database of the laboratory of bacteriology and extraction from the PMIS. Syphilis cases were defined by both positive TPHA and VDRL tests.
The number of positive serology testing was increased eightfold within ten years. Among the 36 patients with syphilis hospitalized cases, 97% were male, aged 17 to 75 years. Eighteen were HIV-infected patients. Among them, 94% were homosexuals and 67% had a history of sexually transmitted infections. The mean time between symptoms and diagnosis was significantly higher in non HIV-infected patients. Clinical forms of syphilis were cutaneomucous secondary syphilis with frequent systemic symptoms for 33%, neurosyphilis, including frequent uveitis for 50%, and gummatous tertiary syphilis involving bones for one patient. Secondary syphilis cases were treated with one to three doses of benzathine penicillin G. Late syphilis and cases of neurosyphilis were treated with penicillin G or ceftriaxone. Neurosensory sequelae accounted for 39% neurosyphilis cases.
This study highlights the incidence increase of syphilis cases in France, frequent poor prognosis of neurosyphilis cases, and diagnosis difficulties, particularly in non HIV-infected patients. This emphasizes the broader use of syphilis serology for compatible medical situations.
The present work focuses on the development of a physically-based model for large deformation stress–strain response and anisotropic damage in rubber-toughened glassy polymers. The main features ...leading to a microstructural evolution (regarding cavitation, void aspect ratio, matrix plastic anisotropy and rubbery phase deformation) in rubber-toughened glassy polymers are introduced in the proposed constitutive model. The constitutive response of the glassy polymer matrix is modelled using the hyperelastic–viscoplastic model of
Boyce et al. (1988, 2000). The deformation mechanisms of the matrix material are accounted for by two resistances: an elastic–viscoplastic isotropic intermolecular resistance acting in parallel with a visco-hyperelastic anisotropic network resistance, each resistance being modified to account for damage effects by void growth with a variation of the void aspect ratio. The effective contribution of the hyperelastic particles to the overall composite behaviour is taken into account by treating the overall system in a composite scheme framework. The capabilities of the proposed constitutive model are checked by comparing experimental data with numerical simulations. The deformation behaviour of rubber-toughened poly(methyl methacrylate) was investigated experimentally in tension at a temperature of 80
°C and for different constant true strain rates monitored by a video-controlled technique. The reinforcing phase is of the soft core–hard shell type and its diameter is of the order of one hundred nanometers. The particle volume fraction was adjusted from 15% to 45% by increments of 5%. The stress–strain response and the inelastic volumetric strain are found to depend markedly on particle volume fraction. For a wide range of rubber volume fractions, the model simulations are in good agreement with the experimental results. Finally, a parametric analysis demonstrates the importance of accounting for void shape, matrix plastic anisotropy and rubber content.
Abstract
The liquid argon ionization current in a sampling calorimeter cell can be analyzed to determine the energy of detected particles. In practice, experimental artifacts such as pileup and ...electronic noise make the inference of energy from current a difficult process. The beam intensity of the Large Hadron Collider will be significantly increased during the Phase-II long shut-down of 2025–2027. Signal processing techniques that are used to extract the energy of detected particles in the ATLAS detector will suffer a significant loss in performance under these conditions. This paper compares the presently used optimal filter technique to convolutional neural networks for energy reconstruction in the ATLAS liquid argon hadronic end cap calorimeter. In particular, it is shown that convolutional neural networks trained with an appropriately tuned and novel loss function are able to outperform the optimal filter technique.
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