International registry on splanchnic vein thrombosis: description of the study population

Background: Splanchnic vein thrombosis (SVT) is an uncommon, butpotentially life-threatening disease. Aim of this ISTH based registryis to improve the knowledge on SVT by studying a large, international,unselected population.Methods: Consecutive patients with objectively diagnosed SVT areeligible for the registry. Information on clinical presentations, diagnosticapproaches, risk factors, therapeutic approaches, and recurrencesof SVT, bleedings and deaths at a 2 year follow up are enteredon a website database (www.svt.altervista.org). We planned a samplesize of 500 patients, including all sites of thrombosis.Results: As of December 31st, 2010, 429 patients with SVT (85.8%of the planned sample) have been enrolled at 25 centres from sevencountries. The mean age is 52.6 years (range 16-85 years); 62.2% aremales, 67.8% are Caucasians, and 31.2% Asians. SVT occurred inmultiple vein segments in 36.4% of patients, 40.5% of patients hadisolated portal vein thrombosis, 11.9% of patients had mesentericvein thrombosis, 7.5% had supra-hepatic vein thrombosis, and 3.6%had splenic vein thrombosis. Abdominal pain was the most commonsymptom occurring in 56.6% of the patients; 9.5% of patients hadgastrointestinal bleeding at the time of diagnosis; 25.4% of patientswith SVT were asymptomatic. Mean time between onset of symptomsand diagnosis was 7.4 days. Objective diagnosis was obtained withabdominal CT in 79.9% of patients. Most common risk factors atthe time of diagnosis included cancer (24.1%), cirrhosis (23.1%), andhematological disorders (15.4%); in 15.9% of patients SVT was idiopathic.Most patients were treated with anticoagulant drugs: 30.8%with parenteral drugs only, 56.9% with parenteral drugs followed byvitamin K antagonists.Conclusions: SVT is a major challenge for experts in thrombosis andhemostasis. Large collaborative studies are necessary to improve theunderstanding and the management of this heterogeneous disease.

African tick-bite fever: a new entity in the differential diagnosis of multiple eschars in travelers. Description of five cases imported from South Africa to Switzerland.

African tick-bite fever (ATBF) is a newly described spotted fever rickettsiosis that frequently presents with multiple eschars in travelers returning from sub-Saharan Africa and, to a lesser extent, from the West Indies. It is caused by the bite of an infected Amblyomma tick, whose hunting habits explain the typical presence of multiple inoculation skin lesions and the occurrence of clustered cases. The etiological agent of ATBF is Rickettsia africae, an emerging tick-borne pathogenic bacterium. We describe herein a cluster of five cases of ATBF occurring in Swiss travelers returning from South Africa. The co-incidental infections in these five patients and the presence of multiple inoculation eschars, two features pathognomonic of this rickettsial disease, suggested the diagnosis of ATBF. Indeed, the presence of at least one inoculation eschar is observed in 53-100% of cases and multiple eschars in 21-54%. Two patients presented regional lymphadenitis and one a mild local lymphangitis. Though a cutaneous rash is described in 15-46% of cases, no rash was observed in our series. ATBF was confirmed by serology. Thus, ATBF has recently emerged as one of the most important causes of flu-like illness in travelers returning from Southern Africa. The presence of one or multiple eschars of inoculation is an important clinical clue to the diagnosis. It can be confirmed by serology or by PCR of a biopsy of the eschar. Culture can also be done in reference laboratories. Dermatologists and primary care physicians should know this clinical entity, since an inexpensive and efficient treatment is available.

Morphological and physiological species-dependent characteristics of the rodent Grueneberg ganglion.

In the mouse, the Grueneberg ganglion (GG) is an olfactory subsystem implicated both in chemo- and thermo-sensing. It is specifically involved in the recognition of volatile danger cues such as alarm pheromones and structurally-related predator scents. No evidence for these GG sensory functions has been reported yet in other rodent species. In this study, we used a combination of histological and physiological techniques to verify the presence of a GG and investigate its function in the rat, hamster, and gerbil comparing with the mouse. By scanning electron microscopy (SEM) and transmitted electron microscopy (TEM), we found isolated or groups of large GG cells of different shapes that in spite of their gross anatomical similarities, display important structural differences between species. We performed a comparative and morphological study focusing on the conserved olfactory features of these cells. We found fine ciliary processes, mostly wrapped in ensheating glial cells, in variable number of clusters deeply invaginated in the neuronal soma. Interestingly, the glial wrapping, the amount of microtubules and their distribution in the ciliary processes were different between rodents. Using immunohistochemistry, we were able to detect the expression of known GG proteins, such as the membrane guanylyl cyclase G and the cyclic nucleotide-gated channel A3. Both the expression and the subcellular localization of these signaling proteins were found to be species-dependent. Calcium imaging experiments on acute tissue slice preparations from rodent GG demonstrated that the chemo- and thermo-evoked neuronal responses were different between species. Thus, GG neurons from mice and rats displayed both chemo- and thermo-sensing, while hamsters and gerbils showed profound differences in their sensitivities. We suggest that the integrative comparison between the structural morphologies, the sensory properties, and the ethological contexts supports species-dependent GG features prompted by the environmental pressure.

Quality Assessment of Cardiac Magnetic Resonance Images at 1.5/3.0 T: Description and Validation of Standardized Criteria

PURPOSE: Cardiovascular magnetic resonance (CMR) has become a robust and important diagnostic imaging modality in cardiovascular medicine. However,insufficient image quality may compromise its diagnostic accuracy. No standardized criteria are available to assess the quality of CMR studies. We aimed todescribe and validate standardized criteria to evaluate the quality of CMR studies including: a) cine steady-state free precession, b) delayed gadoliniumenhancement, and c) adenosine stress first-pass perfusion. These criteria will serve for the assessment of the image quality in the setting of the Euro-CMR registry.METHOD AND MATERIALS: First, a total of 45 quality criteria were defined (35 qualitative criteria with a score from 0-3, and 10 quantitative criteria). Thequalitative score ranged from 0 to 105. The lower the qualitative score, the better the quality. The quantitative criteria were based on the absolute signal intensity (delayed enhancement) and on the signal increase (perfusion) of the anterior/posterior left ventricular wall after gadolinium injection. These criteria were then applied in 30 patients scanned with a 1.5T system and in 15 patients scanned with a 3.0T system. The examinations were jointly interpreted by 3 CMR experts and 1 study nurse. In these 45 patients the correlation between the results of the quality assessment obtained by the different readers was calculated.RESULTS: On the 1.5T machine, the mean quality score was 3.5. The mean difference between each pair of observers was 0.2 (5.7%) with a mean standarddeviation of 1.4. On the 3.0T machine, the mean quality score was 4.4. The mean difference between each pair of onservers was 0.3 (6.4%) with a meanstandard deviation of 1.6. The quantitative quality assessments between observers were well correlated for the 1.5T machine: R was between 0.78 and 0.99 (pCONCLUSION: The described criteria for the assessment of CMR image quality are robust and have a low inter-observer variability, especially on 1.5T systems.CLINICAL RELEVANCE/APPLICATION: These criteria will allow the standardization of CMR examinations. They will help to improve the overall quality ofexaminations and the comparison between clinical studies.

Biochemical, morphological and content characterization of synaptobrevin 2-expressing vesicles in astrocytes

Neuron-astrocyte reciprocal communication at synapses has emerged as a novel signalling pathway in brain function. Astrocytes sense the level of synaptic activity and, in turn, influence its efficacy through the regulated release of ''glio- transmitters'' such as glutamate, ATP or D-serine. A calcium- dependent exocytosis is proposed to drive the release of gliotransmitters but its existence is still debated. To shed light onto the mechanisms controlling the storage and the release of gliotransmitters and namely D-serine, we have developed a new method for the immunoisolation of synaptobrevin 2-positive vesicles from rat cortical astrocytes in culture. The purified organelles are clear round shape vesicles of excellent purity as judged by electron microscopy. Immunoblotting analysis revealed that isolated vesicles contain most of the major proteins already described for neuron-derived vesicles. In addition, we have analyzed the content for various amino acids of these vesicles by means of chiral capillary electro- phoresis coupled to laser-induced fluorescence detection and liquid chromatography coupled to mass spectrometry. Post- embedding immunogold labelling of the rat neocortex and hippocampus further revealed the expression of D-serine and glutamate in astrocyte processes contacting excitatory sy- napses. Our results provide significant support for the existence of secretory glial vesicles storing chemical substances like D- serine and glutamate and thus point to the co-release of amino acids by exocytosis in astrocytes.

Characterization of the Morphological and Molecular Changes Associated with Diabetic Peripheral Neuropathy in Type 2 Diabetes

More than 246 million individuals worldwide are affected by diabetes mellitus (DM) and this number is rapidly increasing (http://www.eatlas. idf.org). 90% of all diabetic patients have type 2 DM, which is characterized by insulin resistance and b-cell dysfunction. Even though diabetic peripheral neuropathy (DPN) is the major chronic complication of DM its underlying pathophysiological mechanisms still remain unknown. To get more insight into the DPN associated with type 2 DM, we characterized the rodent model of this form of diabetes, the db/db mice. The progression of pathological changes in db/db mice mimics the ones observed in humans: increase of the body weight, insulin insensitivity, elevated blood glucose level and reduction in nerve conduction velocity (NCV). Decreased NCV, present in many peripheral neuropathies, is usually associated with demyelination of peripheral nerves. However, our detailed analysis of the sciatic nerves of db/db mice exposed for 4 months to hyperglycemia, failed to reveal any signs of demyelination in spite of significantly reduced NCV in these animals. We therefore currently focus our analysis on the structure of Nodes of Ranvier, regions of intense axo-glial interactions, which also play a crucial role in rapid saltatory impulse conduction. In addition we are also evaluating molecular changes in somas of sensory neurons projecting through sciatic nerve, which are localized in the dorsal root ganglia. We hope that the combination of these approaches will shed light on molecular alterations leading to DPN as a consequence of type 2 DM.

iLOGP: A Simple, Robust, and Efficient Description of n-Octanol/Water Partition Coefficient for Drug Design Using the GB/SA Approach.

The n-octanol/water partition coefficient (log Po/w) is a key physicochemical parameter for drug discovery, design, and development. Here, we present a physics-based approach that shows a strong linear correlation between the computed solvation free energy in implicit solvents and the experimental log Po/w on a cleansed data set of more than 17,500 molecules. After internal validation by five-fold cross-validation and data randomization, the predictive power of the most interesting multiple linear model, based on two GB/SA parameters solely, was tested on two different external sets of molecules. On the Martel druglike test set, the predictive power of the best model (N = 706, r = 0.64, MAE = 1.18, and RMSE = 1.40) is similar to six well-established empirical methods. On the 17-drug test set, our model outperformed all compared empirical methodologies (N = 17, r = 0.94, MAE = 0.38, and RMSE = 0.52). The physical basis of our original GB/SA approach together with its predictive capacity, computational efficiency (1 to 2 s per molecule), and tridimensional molecular graphics capability lay the foundations for a promising predictor, the implicit log P method (iLOGP), to complement the portfolio of drug design tools developed and provided by the SIB Swiss Institute of Bioinformatics.

Scale-dependent adaptive evolution and morphological convergence to climatic niche in Californian eriogonoids (Polygonaceae)

Aim Macroevolutionary patterns and processes change substantially depending on levels of taxonomic and ecological organization, and the resolution of environmental and spatial variability. In comparative methods, the resolution of environmental and spatial variability often defines the number of selective regimes used to test whether phenotypic characteristics are adaptively correlated with the environment. Here, we examine how investigator choice of the number of selective regimes, determined by varying the resolution of among-species variability in the species climatic niche (hereafter called ecological scale'), influences trait morphological diversification among Eriogonoideae species. We assess whether adaptive or neutral processes drive the evolution of several morphological traits in these species. Location South-western North America. Methods We applied a phylogenetic framework of three evolutionary models to four morphological traits and the climatic niches of Eriogonoideae (in the buckwheat family, Polygonaceae). We tested whether morphological traits evolve in relation to climate by adaptive or neutral process, and whether the resulting patterns of morphological variability are conserved or convergent across the clade. We inspected adaptive models of evolution under different levels of resolution of among-species variability of the climatic niche. Results We show that morphological traits and climate niches of Eriogonoideae species are not phylogenetically conserved. Further, adaptive evolution of phenotypic traits is specific to climatic niche occupancy across this clade. Finally, the likely evolutionary process and the level of detectable niche conservatism change depending on the resolution of environmental variability of the climatic niche. Main conclusions Our study demonstrates the need to consider both the resolution of environmental variability and alternative evolutionary models to understand the morphological diversification that accompanies divergent adaptive evolution of lineages to climatic conditions.

A neuronal gamma oscillatory signature during morphological unification in the left occipitotemporal junction.

Morphology is the aspect of language concerned with the internal structure of words. In the past decades, a large body of masked priming (behavioral and neuroimaging) data has suggested that the visual word recognition system automatically decomposes any morphologically complex word into a stem and its constituent morphemes. Yet the reliance of morphology on other reading processes (e.g., orthography and semantics), as well as its underlying neuronal mechanisms are yet to be determined. In the current magnetoencephalography study, we addressed morphology from the perspective of the unification framework, that is, by applying the Hold/Release paradigm, morphological unification was simulated via the assembly of internal morphemic units into a whole word. Trials representing real words were divided into words with a transparent (true) or a nontransparent (pseudo) morphological relationship. Morphological unification of truly suffixed words was faster and more accurate and additionally enhanced induced oscillations in the narrow gamma band (60-85 Hz, 260-440 ms) in the left posterior occipitotemporal junction. This neural signature could not be explained by a mere automatic lexical processing (i.e., stem perception), but more likely it related to a semantic access step during the morphological unification process. By demonstrating the validity of unification at the morphological level, this study contributes to the vast empirical evidence on unification across other language processes. Furthermore, we point out that morphological unification relies on the retrieval of lexical semantic associations via induced gamma band oscillations in a cerebral hub region for visual word form processing.

Quality assessment of cardiovascular magnetic resonance in the setting of the European CMR registry: description and validation of standardized criteria.

BACKGROUND: Cardiovascular magnetic resonance (CMR) has become an important diagnostic imaging modality in cardiovascular medicine. However, insufficient image quality may compromise its diagnostic accuracy. We aimed to describe and validate standardized criteria to evaluate a) cine steady-state free precession (SSFP), b) late gadolinium enhancement (LGE), and c) stress first-pass perfusion images. These criteria will serve for quality assessment in the setting of the Euro-CMR registry. METHODS: Thirty-five qualitative criteria were defined (scores 0-3) with lower scores indicating better image quality. In addition, quantitative parameters were measured yielding 2 additional quality criteria, i.e. signal-to-noise ratio (SNR) of non-infarcted myocardium (as a measure of correct signal nulling of healthy myocardium) for LGE and % signal increase during contrast medium first-pass for perfusion images. These qualitative and quantitative criteria were assessed in a total of 90 patients (60 patients scanned at our own institution at 1.5T (n=30) and 3T (n=30) and in 30 patients randomly chosen from the Euro-CMR registry examined at 1.5T). Analyses were performed by 2 SCMR level-3 experts, 1 trained study nurse, and 1 trained medical student. RESULTS: The global quality score was 6.7±4.6 (n=90, mean of 4 observers, maximum possible score 64), range 6.4-6.9 (p=0.76 between observers). It ranged from 4.0-4.3 for 1.5T (p=0.96 between observers), from 5.9-6.9 for 3T (p=0.33 between observers), and from 8.6-10.3 for the Euro-CMR cases (p=0.40 between observers). The inter- (n=4) and intra-observer (n=2) agreement for the global quality score, i.e. the percentage of assignments to the same quality tertile ranged from 80% to 88% and from 90% to 98%, respectively. The agreement for the quantitative assessment for LGE images (scores 0-2 for SNR <2, 2-5, >5, respectively) ranged from 78-84% for the entire population, and 70-93% at 1.5T, 64-88% at 3T, and 72-90% for the Euro-CMR cases. The agreement for perfusion images (scores 0-2 for %SI increase >200%, 100%-200%,<100%, respectively) ranged from 81-91% for the entire population, and 76-100% at 1.5T, 67-96% at 3T, and 62-90% for the Euro-CMR registry cases. The intra-class correlation coefficient for the global quality score was 0.83. CONCLUSIONS: The described criteria for the assessment of CMR image quality are robust with a good inter- and intra-observer agreement. Further research is needed to define the impact of image quality on the diagnostic and prognostic yield of CMR studies.

Description of a tertiary swiss university hospital palliative population based on the International Classifiaction of Disease (ICD) : a retrospective pilot study

Introduction : L'équipe mobile de soins palliatifs intra hospitalière (EMSP) du Centre Hospitalier Universitaire Vaudois (CHUV) a été mise en place en 1996. Il s'agit d'une des premières équipes interdisciplinaire de consultants mise à disposition d'un hôpital tertiaire. Le CHUV est l'hôpital de proximité de la ville de Lausanne (850 lits) mais aussi un hôpital de référence pour le reste du canton. En 2007, il y a eu 38'359 patients hospitalisés au CHUV. Les facteurs d'évaluation du taux d'utilisation d'une équipe mobile de soins palliatifs consultantes sont variés et complexes. Plusieurs méthodes sont décrites dans la littérature pour tenter de répondre à cette problématique. Avant de pouvoir évaluer l'utilisation de notre équipe mobile consultante de soins palliatifs intra hospitalière, il nous est apparu nécessaire de mieux décrire et définir la population qui meurt dans notre institution. McNamara et collègues ont proposé des critères qui classifient une population palliative comme « minimale », « intermédiaire » ou « maximale ». L'objectif de cette étude est de déterminer le taux de patients décédés au CHUV sur une période de 4 mois (Γ1 février au 31 mai 2007) suivie par notre EMSP en utilisant la méthode de classification «minimal » et « maximal ». Méthode : les archives médicales du CHUV ont été analysées pour chaque patient adulte décédé pendant la période sélectionnée. Les populations « maximal » et « minimal » de ces patients ont été ensuite déterminées selon des critères basés sur les codes diagnostiques figurants sur les certificats de décès. De ces deux populations, nous avons identifié à partir de notre base de données, les patients qui ont été suivie par notre EMSP. Le CHUV utilise les mêmes codes diagnostiques (International Classification of Disease, ICD) que ceux utilisés dans la classification de McNamara. Une recherche pilote effectuée dans les archives médicales du CHUV manuellement en analysant en profondeur l'ensemble du dossier médical a révélé que la classification de la population « minimal » pouvait être biaisée notamment en raison d'une confusion entre la cause directe du décès (complication d'une maladie) et la maladie de base. Nous avons estimé le pourcentage d'erreur de codification en analysé un échantillon randomisé de patients qui remplissait les critères « minimal ». Résultats : sur un total de 294 décès, 263 (89%) remplissaient initialement les critères « maximal » et 83 (28%) les critères «minimal», l'analyse de l'échantillon randomisé de 56 dossiers de patients sur les 180 qui ne remplissaient pas les critères « minimal » ont révélé que 21 (38%) auraient dus être inclus dans la population « minimal ». L'EMSP a vu 67/263 (25.5%) de la population palliative « maximal » et 56/151 (37.1%) de la population palliative « minimal ». Conclusion : cette étude souligne l'utilité de la méthode proposée par McNamara pour déterminer la population de patients palliatifs. Cependant, notre travail illustre aussi une limite importante de l'estimation de la population « minima » en lien avec l'imprécision des causes de décès figurant sur les certificats de décès de notre institution. Nos résultats mettent aussi en lumière que l'EMSP de notre institution est clairement sous- utilisée. Nous prévoyons une étude prospective de plus large envergure utilisant la même méthodologie afin d'approfondir les résultats de cette étude pilote.

Quality of assessement of CMR images in the setting of the European cardiovascular magnetic resonance registry : description and validation of standardized criteria

l'imagerie par résonance magnétique (IRMC) est une technologie utilisée depuis les aimées quatre¬-vingts dans le monde de la cardiologie. Cette technique d'imagerie non-invasive permet d'acquérir Ses images du coeur en trois dimensions, dans n'importe quel, plan, sans application de radiation, et en haute résolution. Actuellement, cette technique est devenue un référence dans l'évaluation et 'l'investigation de différentes pathologies cardiaques. La morphologie cardiaque, la fonction des ventricules ainsi que leur contraction, la perfusion tissulaire ainsi que la viabilité tissulaire peuvent être caractérisés en utilisant différentes séquences d'imagerie. Cependant, cette technologie repose sur des principes physiques complexes et la mise en pratique de cette technique se heurte à la difficulté d'évaluer un organe en mouvement permanent. L'IRM cardiaque est donc sujette à différents artefacts qui perturbent l'interprétation des examens et peuvent diminuer la précision diagnostique de cette technique. A notre connaissance, la plupart des images d'IRMC sont analysées et interprétées sans évaluation rigoureuse de la qualité intrinsèque de l'examen. Jusqu'à présent, et à notre connaissance, aucun critère d'évaluation de la qualité des examens d'IRMC n'a été clairement déterminé. L'équipe d'IRMC du CHUV, dirigée par le Prof J. Schwitter, a recensé une liste de 35 critères qualitatifs et 12 critères quantitatifs évaluant la qualité d'un examen d'IRMC et les a introduit dans une grille d'évaluation. L'objet de cette étude est de décrire et de valider la reproductibilité des critères figurant dans cette grille d'évaluation, par l'interprétation simultanée d'examens IRMC par différents observateurs (cardiologues spécialisés en IRM, étudiant en médecine, infirmière spécialisée). Notre étude a permis de démontrer que les critères définis pour l'évaluation des examens d'IRMC sont robustes, et permettent une bonne reproductibilité intra- et inter-observateurs. Cette étude valide ainsi l'utilisation de ces critères de qualité dans le cadre de l'imagerie par résonance magnétique cardiaque. D'autres études sont encore nécessaires afin de déterminer l'impact de la qualité de l'image sur la précision diagnostique de cette technique. Les critères standardisés que nous avons validés seront utilisés pour évaluer la qualité des images dans le cadre d'une étude à échelle européenne relative à l'IRMC : "l'EuroCMR registry". Parmi les autres utilités visées par ces critères de qualité, citons notamment la possibilité d'avoir une référence d'évaluation de la qualité d'examen pour toutes les futures études cliniques utilisant la technologie d'IRMC, de permettre aux centres d'IRMC de quantifier leur niveau de qualité, voire de créer un certificat de standard de qualité pour ces centres, d'évaluer la reproductibilité de l'évaluation des images par différents observateurs d'un même centre, ou encore d'évaluer précisément la qualité des séquences développées à l'avenir dans le monde de l'IRMC.