The use of external mesh reinforcement to reduce intimal hyperplasia and preserve the structure of human saphenous veins.

The saphenous vein is the conduit of choice in bypass graft procedures. Haemodynamic factors play a major role in the development of intimal hyperplasia (IH), and subsequent bypass failure. To evaluate the potential protective effect of external reinforcement on such a failure, we developed an ex vivo model for the perfusion of segments of human saphenous veins under arterial shear stress. In veins submitted to pulsatile high pressure (mean pressure at 100 mmHg) for 3 or 7 days, the use of an external macroporous polyester mesh 1) prevented the dilatation of the vessel, 2) decreased the development of IH, 3) reduced the apoptosis of smooth muscle cells, and the subsequent fibrosis of the media layer, 4) prevented the remodelling of extracellular matrix through the up-regulation of matrix metalloproteinases (MMP-2, MMP-9) and plasminogen activator type I. The data show that, in an experimental ex vivo setting, an external scaffold decreases IH and maintains the integrity of veins exposed to arterial pressure, via increase in shear stress and decrease wall tension, that likely contribute to trigger selective molecular and cellular changes.

Ignition of a human body by a modest external source: a case report.

A case of sustained combustion of a human body that occurred in 2006 in Geneva, Switzerland, is presented. The body of a man was discovered at home and found to have been almost completely incinerated between the knees and the mid-chest, with less damage to the head, arms, lower legs and feet. His dog was also found dead just behind the house door. The external source of ignition was most likely a cigarette or a cigar. The chair in which the man had been sitting was largely consumed while other objects in the room exhibited only a brown oily or greasy coating and were virtually undamaged. Toxicological analyses carried out on the blood from the lower legs showed low levels of desalkylflurazepam. Alcohol concentration was 1.10 per thousand, carboxyhaemoglobin levels were 12% and cyanide concentration was 0.05 mg/L. Toxicological analyses carried out on the dog's blood showed carboxyhaemoglobin levels at 65%.

Simulation of stromatolite growth using diffusion-limited aggregation and a discrete model of biogeochemical exchanges in microbial mat

Resume : Mieux comprendre les stromatolithes et les tapis microbiens est un sujet important en biogéosciences puisque cela aide à l'étude des premières formes de vie sur Terre, a mieux cerner l'écologie des communautés microbiennes et la contribution des microorganismes a la biominéralisation, et même à poser certains fondements dans les recherches en exobiologie. D'autre part, la modélisation est un outil puissant utilisé dans les sciences naturelles pour appréhender différents phénomènes de façon théorique. Les modèles sont généralement construits sur un système d'équations différentielles et les résultats sont obtenus en résolvant ce système. Les logiciels disponibles pour implémenter les modèles incluent les logiciels mathématiques et les logiciels généraux de simulation. L'objectif principal de cette thèse est de développer des modèles et des logiciels pour aider a comprendre, via la simulation, le fonctionnement des stromatolithes et des tapis microbiens. Ces logiciels ont été développés en C++ en ne partant d'aucun pré-requis de façon a privilégier performance et flexibilité maximales. Cette démarche permet de construire des modèles bien plus spécifiques et plus appropriés aux phénomènes a modéliser. Premièrement, nous avons étudié la croissance et la morphologie des stromatolithes. Nous avons construit un modèle tridimensionnel fondé sur l'agrégation par diffusion limitée. Le modèle a été implémenté en deux applications C++: un moteur de simulation capable d'exécuter un batch de simulations et de produire des fichiers de résultats, et un outil de visualisation qui permet d'analyser les résultats en trois dimensions. Après avoir vérifié que ce modèle peut en effet reproduire la croissance et la morphologie de plusieurs types de stromatolithes, nous avons introduit un processus de sédimentation comme facteur externe. Ceci nous a mené a des résultats intéressants, et permis de soutenir l'hypothèse que la morphologie des stromatolithes pourrait être le résultat de facteurs externes autant que de facteurs internes. Ceci est important car la classification des stromatolithes est généralement fondée sur leur morphologie, imposant que la forme d'un stromatolithe est dépendante de facteurs internes uniquement (c'est-à-dire les tapis microbiens). Les résultats avancés dans ce mémoire contredisent donc ces assertions communément admises. Ensuite, nous avons décidé de mener des recherches plus en profondeur sur les aspects fonctionnels des tapis microbiens. Nous avons construit un modèle bidimensionnel de réaction-diffusion fondé sur la simulation discrète. Ce modèle a été implémenté dans une application C++ qui permet de paramétrer et exécuter des simulations. Nous avons ensuite pu comparer les résultats de simulation avec des données du monde réel et vérifier que le modèle peut en effet imiter le comportement de certains tapis microbiens. Ainsi, nous avons pu émettre et vérifier des hypothèses sur le fonctionnement de certains tapis microbiens pour nous aider à mieux en comprendre certains aspects, comme la dynamique des éléments, en particulier le soufre et l'oxygène. En conclusion, ce travail a abouti à l'écriture de logiciels dédiés à la simulation de tapis microbiens d'un point de vue tant morphologique que fonctionnel, suivant deux approches différentes, l'une holistique, l'autre plus analytique. Ces logiciels sont gratuits et diffusés sous licence GPL (General Public License). Abstract : Better understanding of stromatolites and microbial mats is an important topic in biogeosciences as it helps studying the early forms of life on Earth, provides clues re- garding the ecology of microbial ecosystems and their contribution to biomineralization, and gives basis to a new science, exobiology. On the other hand, modelling is a powerful tool used in natural sciences for the theoretical approach of various phenomena. Models are usually built on a system of differential equations and results are obtained by solving that system. Available software to implement models includes mathematical solvers and general simulation software. The main objective of this thesis is to develop models and software able to help to understand the functioning of stromatolites and microbial mats. Software was developed in C++ from scratch for maximum performance and flexibility. This allows to build models much more specific to a phenomenon rather than general software. First, we studied stromatolite growth and morphology. We built a three-dimensional model based on diffusion-limited aggregation. The model was implemented in two C++ applications: a simulator engine, which can run a batch of simulations and produce result files, and a Visualization tool, which allows results to be analysed in three dimensions. After verifying that our model can indeed reproduce the growth and morphology of several types of stromatolites, we introduced a sedimentation process as an external factor. This lead to interesting results, and allowed to emit the hypothesis that stromatolite morphology may be the result of external factors as much as internal factors. This is important as stromatolite classification is usually based on their morphology, imposing that a stromatolite shape is dependant on internal factors only (i.e. the microbial mat). This statement is contradicted by our findings, Second, we decided to investigate deeper the functioning of microbial mats, We built a two-dimensional reaction-diffusion model based on discrete simulation, The model was implemented in a C++ application that allows setting and running simulations. We could then compare simulation results with real world data and verify that our model can indeed mimic the behaviour of some microbial mats. Thus, we have proposed and verified hypotheses regarding microbial mats functioning in order to help to better understand them, e.g. the cycle of some elements such as oxygen or sulfur. ln conclusion, this PhD provides a simulation software, dealing with two different approaches. This software is free and available under a GPL licence.

External validation of the ASTRAL score to predict 3- and 12-month functional outcome in the China National Stroke Registry.

BACKGROUND AND PURPOSE: The ASTRAL score was recently introduced as a prognostic tool for acute ischemic stroke. It predicts 3-month outcome reliably in both the derivation and the validation European cohorts. We aimed to validate the ASTRAL score in a Chinese stroke population and moreover to explore its prognostic value to predict 12-month outcome. METHODS: We applied the ASTRAL score to acute ischemic stroke patients admitted to 132 study sites of the China National Stroke Registry. Unfavorable outcome was assessed as a modified Rankin Scale score >2 at 3 and 12 months. Areas under the curve were calculated to quantify the prognostic value. Calibration was assessed by comparing predicted and observed probability of unfavorable outcome using Pearson correlation coefficient. RESULTS: Among 3755 patients, 1473 (39.7%) had 3-month unfavorable outcome. Areas under the curve for 3 and 12 months were 0.82 and 0.81, respectively. There was high correlation between observed and expected probability of unfavorable 3- and 12-month outcome (Pearson correlation coefficient: 0.964 and 0.963, respectively). CONCLUSIONS: ASTRAL score is a reliable tool to predict unfavorable outcome at 3 and 12 months after acute ischemic stroke in the Chinese population. It is a useful tool that can be readily applied in clinical practice to risk-stratify acute stroke patients.

Role of seipin in lipid droplet morphology and hepatitis C virus life cycle.

Infectious hepatitis C virus (HCV) particle assembly starts at the surface of lipid droplets, cytoplasmic organelles responsible for neutral fat storage. We analysed the relationship between HCV and seipin, a protein involved in lipid droplet maturation. Although seipin overexpression did not affect the total mean volume occupied by lipid droplets nor the total triglyceride and cholesterol ester levels per cell, it caused an increase in the mean diameter of lipid droplets by 60 %, while decreasing their total number per cell. The latter two effects combined resulted in a 34 % reduction of the total outer surface area of lipid droplets per cell, with a proportional decrease in infectious viral particle production, probably due to a defect in particle assembly. These results suggest that the available outer surface of lipid droplets is a critical factor for HCV release, independent of the neutral lipid content of the cell.

Epistemological tensions between linguistic description and ordinary speakers' intuitive knowledge: examples from French verb morphology

In this article, I address epistemological questions regarding the status of linguistic rules and the pervasive--though seldom discussed--tension that arises between theory-driven object perception by linguists on the one hand, and ordinary speakers' possible intuitive knowledge on the other hand. Several issues will be discussed using examples from French verb morphology, based on the 6500 verbs from Le Petit Robert dictionary (2013).

Mutations in LONP1, a mitochondrial matrix protease, cause CODAS syndrome.

Cerebral, ocular, dental, auricular, skeletal anomalies (CODAS) syndrome (MIM 600373) was first described and named by Shehib et al, in 1991 in a single patient. The anomalies referred to in the acronym are as follows: cerebral-developmental delay, ocular-cataracts, dental-aberrant cusp morphology and delayed eruption, auricular-malformations of the external ear, and skeletal-spondyloepiphyseal dysplasia. This distinctive constellation of anatomical findings should allow easy recognition but despite this only four apparently sporadic patients have been reported in the last 20 years indicating that the full phenotype is indeed very rare with perhaps milder or a typical presentations that are allelic but without sufficient phenotypic resemblance to permit clinical diagnosis. We performed exome sequencing in three patients (an isolated case and a brother and sister sib pair) with classical features of CODAS. Sanger sequencing was used to confirm results as well as for mutation discovery in a further four unrelated patients ascertained via their skeletal features. Compound heterozygous or homozygous mutations in LONP1 were found in all (8 separate mutations; 6 missense, 1 nonsense, 1 small in-frame deletion) thus establishing the genetic basis of CODAS and the pattern of inheritance (autosomal recessive). LONP1 encodes an enzyme of bacterial ancestry that participates in protein turnover within the mitochondrial matrix. The mutations cluster at the ATP-binding and proteolytic domains of the enzyme. Biallelic inheritance and clustering of mutations confirm dysfunction of LONP1 activity as the molecular basis of CODAS but the pathogenesis remains to be explored.

External assessment of the Early Mortality Risk Score in patients with adenocarcinoma undergoing pancreaticoduodenectomy.

BACKGROUND: Pancreaticoduodenectomies (PD) still have a substantial mortality rate. Recently, different scores have been published to predict the mortality risk pre-operatively after PD. This retrospective study was designed to perform an external assessment of an Early Mortality Risk Score (EMRS). METHODS: From 2000 to 2012, all PD cases performed at our institution were documented. Only patients treated for pancreatic head adenocarcinomas were included. Survival time and EMRS (based on age, tumour size, tumour differentiation and comorbidities) were calculated for every patient. Relative risks (RR) of early death 9 and 12 months after PD were then calculated. RESULTS: Of 270 PD for various aetiologies, 120 PD for adenocarcinomas were included. The median follow-up was 37 months, and the overall median survival was 19 months. EMRS of 4 showed a mortality RR of 5.1 at 9 months (P = 0.048) and of 4.5 at 12 months (P = 0.020). CONCLUSIONS: EMRS of 4 is a predictor of tumour-related mortality at 9 and 12 months after PD for adenocarcinoma. The EMRS was externally assessed in our patient cohort and can be implemented in clinical practice. Clinical implications of this score still need to be studied.

External urethral sphincter electromyography in asymptomatic women and the influence of the menstrual cycle.

OBJECTIVE: To investigate by electromyography (EMG), the presence of complex repetitive discharges (CRDs) and decelerating bursts (DBs) in the striated external urethral sphincter during the menstrual cycle in female volunteers with no urinary symptoms and complete bladder emptying. SUBJECTS AND METHODS: Healthy female volunteers aged 20-40 years, with regular menstrual cycles and no urinary symptoms were recruited. Volunteers completed a menstruation chart, urinary symptom questionnaires, pregnancy test, urine dipstick, urinary free flow and post-void ultrasound bladder scan. Exclusion criteria included current pregnancy, use of hormonal medication or contraception, body mass index of >35 kg/m(2) , incomplete voiding and a history of pelvic surgery. Eligible participants underwent an external urethral sphincter EMG, using a needle electrode in the early follicular phase and the mid-luteal phase of their menstrual cycles. Serum oestradiol and progesterone were measured at each EMG test. RESULTS: In all, 119 women enquired about the research and following screening, 18 were eligible to enter the study phase. Complete results were obtained in 15 women. In all, 30 EMG tests were undertaken in the 15 asymptomatic women. Sphincter EMG was positive for CRDs and DBs at one or both phases of the menstrual cycle in eight (53%) of the women. Three had CRDs and DBs in both early follicular and mid-luteal phases. Five had normal EMG activity in the early follicular phase and CRDs and DBs in the mid-luteal phase. No woman had abnormal EMG activity in the early follicular phase and normal activity in the luteal phase. There was no relationship between EMG activity and age, parity or serum levels of oestradiol and progesterone. CONCLUSIONS: CRDs and DB activity in the external striated urethral sphincter is present in a high proportion of asymptomatic young women. This abnormal EMG activity has been shown for the first time to change during the menstrual cycle in individual women. CRDs and DBs are more commonly found in the luteal phase of the menstrual cycle. The importance of CRDs and DBs in the aetiology of urinary retention in young women remains uncertain. The distribution and or quantity of abnormal EMG activity in the external urethral sphincter may be important. In a woman with urinary retention the finding of CRDs and DBs by needle EMG does not automatically establish Fowler's syndrome as the explanation for the bladder dysfunction. Urethral pressure profilometry may be helpful in establishing a diagnosis. Opiate use and psychological stress should be considered in young women with urinary retention.

External Validation of the Prestroke Independence, Sex, Age, National Institutes of Health Stroke Scale (ISAN) Score for Predicting Stroke-Associated Pneumonia in the Athens Stroke Registry.

BACKGROUND AND PURPOSE: The Prestroke Independence, Sex, Age, National Institutes of Health Stroke Scale (ISAN) score was developed recently for predicting stroke-associated pneumonia (SAP), one of the most common complications after stroke. The aim of the present study was to externally validate the ISAN score. METHODS: Data included in the Athens Stroke Registry between June 1992 and December 2011 were used for this analysis. Inclusion criteria were the availability of all ISAN score variables (prestroke independence, sex, age, National Institutes of Health Stroke Scale score). Receiver operating characteristic curves and linear regression analyses were used to determine the discriminatory power of the score and to assess the correlation between actual and predicted pneumonia in the study population. Separate analyses were performed for patients with acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH). RESULTS: The analysis included 3204 patients (AIS: 2732, ICH: 472). The ISAN score demonstrated excellent discrimination in patients with AIS (area under the curve [AUC]: .83 [95% confidence interval {CI}: .81-.85]). In the ICH group, the score was less effective (AUC: .69 [95% CI: .63-.74]). Higher-risk groups of ISAN score were associated with an increased relative risk of SAP; risk increase was more prominent in the AIS population. Predicted pneumonia correlated very well with actual pneumonia (AIS group: R(2) = .885; β-coefficient = .941, P < .001; ICH group: R(2) = .880, β-coefficient = .938, P < .001). CONCLUSIONS: In our external validation in the Athens Stroke Registry cohort, the ISAN score predicted SAP very accurately in AIS patients and demonstrated good discriminatory power in the ICH group. Further validation and assessment of clinical usefulness would strengthen the score's utility further.