The neonatal progeroid syndrome (Wiedemann-Rautenstrauch) and its relationship to Pelizaeus-Merzbacher's disease.

The neuropathology of a clinically well-documented case of the neonatal progeroid syndrome Wiedemann-Rautenstrauch is described. The most striking feature was a nearly complete absence of mature myelin in the brain. When immunohistochemistry for myelin basic protein was applied, some subcortical nerve fibres were accompanied by immature myelin sheaths. The neuropathology corresponds exactly to that of Pelizaeus-Merzbacher disease (Seitelberger type). Furthermore, this morphology, with the presence of myelin basic protein in the absence of mature myelin sheaths is reminiscent of the early stages of myelination in the newborn. From a brief review of the literature on Wiedemann-Rautenstrauch syndrome, we conclude, that the neuropathology of the syndrome is heterogeneous, and that there is relationship between the progeroid aspect and pathological myelination.

Data-driven clustering : new methods and applications

Abstract : This work is concerned with the development and application of novel unsupervised learning methods, having in mind two target applications: the analysis of forensic case data and the classification of remote sensing images. First, a method based on a symbolic optimization of the inter-sample distance measure is proposed to improve the flexibility of spectral clustering algorithms, and applied to the problem of forensic case data. This distance is optimized using a loss function related to the preservation of neighborhood structure between the input space and the space of principal components, and solutions are found using genetic programming. Results are compared to a variety of state-of--the-art clustering algorithms. Subsequently, a new large-scale clustering method based on a joint optimization of feature extraction and classification is proposed and applied to various databases, including two hyperspectral remote sensing images. The algorithm makes uses of a functional model (e.g., a neural network) for clustering which is trained by stochastic gradient descent. Results indicate that such a technique can easily scale to huge databases, can avoid the so-called out-of-sample problem, and can compete with or even outperform existing clustering algorithms on both artificial data and real remote sensing images. This is verified on small databases as well as very large problems. Résumé : Ce travail de recherche porte sur le développement et l'application de méthodes d'apprentissage dites non supervisées. Les applications visées par ces méthodes sont l'analyse de données forensiques et la classification d'images hyperspectrales en télédétection. Dans un premier temps, une méthodologie de classification non supervisée fondée sur l'optimisation symbolique d'une mesure de distance inter-échantillons est proposée. Cette mesure est obtenue en optimisant une fonction de coût reliée à la préservation de la structure de voisinage d'un point entre l'espace des variables initiales et l'espace des composantes principales. Cette méthode est appliquée à l'analyse de données forensiques et comparée à un éventail de méthodes déjà existantes. En second lieu, une méthode fondée sur une optimisation conjointe des tâches de sélection de variables et de classification est implémentée dans un réseau de neurones et appliquée à diverses bases de données, dont deux images hyperspectrales. Le réseau de neurones est entraîné à l'aide d'un algorithme de gradient stochastique, ce qui rend cette technique applicable à des images de très haute résolution. Les résultats de l'application de cette dernière montrent que l'utilisation d'une telle technique permet de classifier de très grandes bases de données sans difficulté et donne des résultats avantageusement comparables aux méthodes existantes.

Silencing of c-Fos expression by microRNA-155 is critical for dendritic cell maturation and function.

MicroRNAs (miRNAs) are small, noncoding RNAs that regulate target mRNAs by binding to their 3' untranslated regions. There is growing evidence that microRNA-155 (miR155) modulates gene expression in various cell types of the immune system and is a prominent player in the regulation of innate and adaptive immune responses. To define the role of miR155 in dendritic cells (DCs) we performed a detailed analysis of its expression and function in human and mouse DCs. A strong increase in miR155 expression was found to be a general and evolutionarily conserved feature associated with the activation of DCs by diverse maturation stimuli in all DC subtypes tested. Analysis of miR155-deficient DCs demonstrated that miR155 induction is required for efficient DC maturation and is critical for the ability of DCs to promote antigen-specific T-cell activation. Expression-profiling studies performed with miR155(-/-) DCs and DCs overexpressing miR155, combined with functional assays, revealed that the mRNA encoding the transcription factor c-Fos is a direct target of miR155. Finally, all of the phenotypic and functional defects exhibited by miR155(-/-) DCs could be reproduced by deregulated c-Fos expression. These results indicate that silencing of c-Fos expression by miR155 is a conserved process that is required for DC maturation and function.

Beyond the 'dyad': a qualitative re-evaluation of the changing clinical consultation.

OBJECTIVE: To identify characteristics of consultations that do not conform to the traditionally understood communication 'dyad', in order to highlight implications for medical education and develop a reflective 'toolkit' for use by medical practitioners and educators in the analysis of consultations. DESIGN: A series of interdisciplinary research workshops spanning 12 months explored the social impact of globalisation and computerisation on the clinical consultation, focusing specifically on contemporary challenges to the clinician-patient dyad. Researchers presented detailed case studies of consultations, taken from their recent research projects. Drawing on concepts from applied sociolinguistics, further analysis of selected case studies prompted the identification of key emergent themes. SETTING: University departments in the UK and Switzerland. PARTICIPANTS: Six researchers with backgrounds in medicine, applied linguistics, sociolinguistics and medical education. One workshop was also attended by PhD students conducting research on healthcare interactions. RESULTS: The contemporary consultation is characterised by a multiplicity of voices. Incorporation of additional voices in the consultation creates new forms of order (and disorder) in the interaction. The roles 'clinician' and 'patient' are blurred as they become increasingly distributed between different participants. These new consultation arrangements make new demands on clinicians, which lie beyond the scope of most educational programmes for clinical communication. CONCLUSIONS: The consultation is changing. Traditional consultation models that assume a 'dyadic' consultation do not adequately incorporate the realities of many contemporary consultations. A paradox emerges between the need to manage consultations in a 'super-diverse' multilingual society, while also attending to increasing requirements for standardised protocol-driven approaches to care prompted by computer use. The tension between standardisation and flexibility requires addressing in educational contexts. Drawing on concepts from applied sociolinguistics and the findings of these research observations, the authors offer a reflective 'toolkit' of questions to ask of the consultation in the context of enquiry-based learning.

Plastid genome characterisation in Brassica and Brassicaceae using a new set of nine SSRs.

We report a new set of nine primer pairs specifically developed for amplification of Brassica plastid SSR markers. The wide utility of these markers is demonstrated for haplotype identification and detection of polymorphism in B. napus, B. nigra, B. oleracea, B. rapa and in related genera Arabidopsis, Camelina, Raphanus and Sinapis. Eleven gene regions (ndhB-rps7 spacer, rbcL-accD spacer, rpl16 intron, rps16 intron, atpB-rbcL spacer, trnE-trnT spacer, trnL intron, trnL-trnF spacer, trnM-atpE spacer, trnR-rpoC2 spacer, ycf3-psaA spacer) were sequenced from a range of Brassica and related genera for SSR detection and primer design. Other sequences were obtained from GenBank/EMBL. Eight out of nine selected SSR loci showed polymorphism when amplified using the new primers and a combined analysis detected variation within and between Brassica species, with the number of alleles detected per locus ranging from 5 (loci MF-6, MF-1) to 11 (locus MF-7). The combined SSR data were used in a neighbour-joining analysis (SMM, D (DM) distances) to group the samples based on the presence and absence of alleles. The analysis was generally able to separate plastid types into taxon-specific groups. Multi-allelic haplotypes were plotted onto the neighbour joining tree. A total number of 28 haplotypes were detected and these differentiated 22 of the 41 accessions screened from all other accessions. None of these haplotypes was shared by more than one species and some were not characteristic of their predicted type. We interpret our results with respect to taxon differentiation, hybridisation and introgression patterns relating to the 'Triangle of U'.

Expression quantitative trait locus mapping across water availability environments reveals contrasting associations with genomic features in Arabidopsis.

The regulation of gene expression is crucial for an organism's development and response to stress, and an understanding of the evolution of gene expression is of fundamental importance to basic and applied biology. To improve this understanding, we conducted expression quantitative trait locus (eQTL) mapping in the Tsu-1 (Tsushima, Japan) × Kas-1 (Kashmir, India) recombinant inbred line population of Arabidopsis thaliana across soil drying treatments. We then used genome resequencing data to evaluate whether genomic features (promoter polymorphism, recombination rate, gene length, and gene density) are associated with genes responding to the environment (E) or with genes with genetic variation (G) in gene expression in the form of eQTLs. We identified thousands of genes that responded to soil drying and hundreds of main-effect eQTLs. However, we identified very few statistically significant eQTLs that interacted with the soil drying treatment (GxE eQTL). Analysis of genome resequencing data revealed associations of several genomic features with G and E genes. In general, E genes had lower promoter diversity and local recombination rates. By contrast, genes with eQTLs (G) had significantly greater promoter diversity and were located in genomic regions with higher recombination. These results suggest that genomic architecture may play an important a role in the evolution of gene expression.

Correlates of insomnia in patients with social phobia: role of depression and anxiety.

The severity of insomnia and the relationships between social fear, anxiety, depression and insomnia were examined in 179 patients with social phobia. Two-thirds of our sample had insomnia. Depression, anxiety, social anxiety, and insomnia were positively correlated. General and social anxiety contributed to insomnia when accounting for depression.

Evaluation de la satisfaction des infirmiers(-ères): développement et validation d'un nouvel outil d'analyse [Evaluation of satisfaction of nurses: development and validation of a new analysis tool]

A new device for the analyses of nurses' satisfaction has been developed and validated on two types of general and intensive treatments at the University Hospital in Vaudois, Switzerland. A questionnaire has been elaborated for identifying the variables linked with characteristics of the nurse's work, as well as personal variables of the employer which could have an influence on the level of satisfaction. In identifying the sources of satisfaction and dissatisfaction, it has been possible to propose recommendations and corrective measures in order to improve the level of global satisfaction of the nursing team.

A fully validated method for the determination of arsenic species in rice and infant cereal products

A full validation of inorganic arsenic (iAs), methylarsonic acid (MA), and dimethyl arsinic acid (DMA) in several types of rice and rice-based infant cereals is reported. The analytical method was developed and validated in two laboratories. The extraction of the As species was performed using nitric acid 0.2 % and hydrogen peroxide 1 %, and the coupled system liquid chromatography-inductively coupled plasma-mass spectrometry (LCICP-MS) was used for speciation measurements. Detection limit (DL), quantification limit, linearity, precision, trueness, accuracy, selectivity, as well as expanded uncertainty for iAs, MA, and DMA were established. The certified reference materials (CRMs) (NMIJ 7503a, NCS ZC73008, NIST SRM 1568a) were used to check the accuracy. The method was shown to be satisfactory in two proficiency tests (PTs). The broad applicability of the method is shown from the results of analysis of 29 samples including several types of rice, rice products, and infant cereal products. Total As ranged from 40.1 to 323.7 μg As kg1. From the speciation results, iAs was predominant, and DMA was detected in some samples while MA was not detected in any sample.

Smart instrumentation for determination of ligament stiffness and ligament balance in total knee arthroplasty.

Ligament balance is an important and subjective task performed during total knee arthroplasty (TKA) procedure. For this reason, it is desirable to develop instruments to quantitatively assess the soft-tissue balance since excessive imbalance can accelerate prosthesis wear and lead to early surgical revision. The instrumented distractor proposed in this study can assist surgeons on performing ligament balance by measuring the distraction gap and applied load. Also the device allows the determination of the ligament stiffness which can contribute a better understanding of the intrinsic mechanical behavior of the knee joint. Instrumentation of the device involved the use of hall-sensors for measuring the distractor displacement and strain gauges to transduce the force. The sensors were calibrated and tested to demonstrate their suitability for surgical use. Results show the distraction gap can be measured reliably with 0.1mm accuracy and the distractive loads could be assessed with an accuracy in the range of 4N. These characteristics are consistent with those have been proposed, in this work, for a device that could assist on performing ligament balance while permitting surgeons evaluation based on his experience. Preliminary results from in vitro tests were in accordance with expected stiffness values for medial collateral ligament (MCL) and lateral collateral ligament (LCL).

Field Monitoring of Curved Girder Bridges with Integral Abutments, TPF-5(169), 2014

Nationally, there are questions regarding the design, fabrication, and erection of horizontally curved steel girder bridges due to unpredicted girder displacements, fit-up, and locked-in stresses. One reason for the concerns is that up to one-quarter of steel girder bridges are being designed with horizontal curvature. There is also an urgent need to reduce bridge maintenance costs by eliminating or reducing deck joints, which can be achieved by expanding the use of integral abutments to include curved girder bridges. However, the behavior of horizontally curved bridges with integral abutments during thermal loading is not well known nor understood. The purpose of this study was to investigate the behavior of horizontal curved bridges with integral abutment (IAB) and semi-integral abutment bridges (SIAB) with a specific interest in the response to changing temperatures. The long-term objective of this effort is to establish guidelines for the use of integral abutments with curved girder bridges. The primary objective of this work was to monitor and evaluate the behavior of six in-service, horizontally curved, steel-girder bridges with integral and semi-integral abutments. In addition, the influence of bridge curvature, skew and pier bearing (expansion and fixed) were also part of the study. Two monitoring systems were designed and applied to a set of four horizontally curved bridges and two straight bridges at the northeast corner of Des Moines, Iowa—one system for measuring strains and movement under long term thermal changes and one system for measuring the behavior under short term, controlled live loading. A finite element model was developed and validated against the measured strains. The model was then used to investigate the sensitivity of design calculations to curvature, skew and pier joint conditions. The general conclusions were as follows: (1) There were no measurable differences in the behavior of the horizontally curved bridges and straight bridges studied in this work under thermal effects. For preliminary member sizing of curved bridges, thermal stresses and movements in a straight bridge of the same length are a reasonable first approximation. (2) Thermal strains in integral abutment and semi-integral abutment bridges were not noticeably different. The choice between IAB and SIAB should be based on life – cycle costs (e.g., construction and maintenance). (3) An expansion bearing pier reduces the thermal stresses in the girders of the straight bridge but does not appear to reduce the stresses in the girders of the curved bridge. (4) An analysis of the bridges predicted a substantial total stress (sum of the vertical bending stress, the lateral bending stress, and the axial stress) up to 3 ksi due to temperature effects. (5) For the one curved integral abutment bridge studied at length, the stresses in the girders significantly vary with changes in skew and curvature. With a 10⁰ skew and 0.06 radians arc span length to radius ratio, the curved and skew integral abutment bridges can be designed as a straight bridge if an error in estimation of the stresses of 10% is acceptable.

Review: Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates.

A. Costanza, K. Weber, S. Gandy, C. Bouras, P. R. Hof, P. Giannakopoulos and A. Canuto (2011) Neuropathology and Applied Neurobiology37, 570-584 Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates Professional boxers and other contact sport athletes are exposed to repetitive brain trauma that may affect motor functions, cognitive performance, emotional regulation and social awareness. The term of chronic traumatic encephalopathy (CTE) was recently introduced to regroup a wide spectrum of symptoms such as cerebellar, pyramidal and extrapyramidal syndromes, impairments in orientation, memory, language, attention, information processing and frontal executive functions, as well as personality changes and behavioural and psychiatric symptoms. Magnetic resonance imaging usually reveals hippocampal and vermis atrophy, a cavum septum pellucidum, signs of diffuse axonal injury, pituitary gland atrophy, dilated perivascular spaces and periventricular white matter disease. Given the partial overlapping of the clinical expression, epidemiology and pathogenesis of CTE and Alzheimer's disease (AD), as well as the close association between traumatic brain injuries (TBIs) and neurofibrillary tangle formation, a mixed pathology promoted by pathogenetic cascades resulting in either CTE or AD has been postulated. Molecular studies suggested that TBIs increase the neurotoxicity of the TAR DNA-binding protein 43 (TDP-43) that is a key pathological marker of ubiquitin-positive forms of frontotemporal dementia (FTLD-TDP) associated or not with motor neurone disease/amyotrophic lateral sclerosis (ALS). Similar patterns of immunoreactivity for TDP-43 in CTE, FTLD-TDP and ALS as well as epidemiological correlations support the presence of common pathogenetic mechanisms. The present review provides a critical update of the evolution of the concept of CTE with reference to its neuropathological definition together with an in-depth discussion of the differential diagnosis between this entity, AD and frontotemporal dementia.