Apport de l'angiographie au vert d'indocyanine (ICG) dans la localisation des néovascularisations chororoidiennes occultes [Value of indocyanine green angiography in localization of occult choroid neovascularization]

PURPOSE: To determine the role of Indocyanin Green (ICG) angiography in localizing occult new vessels associated with age-related macular degeneration (ARMD) and assess the possibilities of ICG guided laser photocoagulations. PATIENTS AND METHODS: Fluorescein and ICG angiographies (IMAGEnet system) of 62 patients with occult new vessels (ONV), serous (SPED) or vascular (VPED) pigment epithelium detachment have been studied. RESULTS: Based on fondoscopic examination and fluorescein angiography, 43 eyes (69%) disclosed ONV, 8 (13%) SPED and 11 (18%) VPED. Choroidal neovascularisation was confirmed by ICG angiography in 37 ONV cases (86%), in 8 (72%) VPED cases, but in no SPED. Conversion of ONV in classical neovascular membranes was possible in 19 ONV cases (44%) and in 6 (54%) VPED cases, making a laser photocoagulation possible in 9 eyes (36%). CONCLUSION: ICG angiography plays an important role in the evaluation, classification and laser treatment of patients with ONV secondary to ARMD.

Treatment of penile carcinoma: to cut or not to cut?

PURPOSE: The aim of this study was to assess the outcome in patients with penile cancer. METHODS AND MATERIALS: A total of 60 patients with penile carcinoma were included. Of the patients, 45 (n = 27) underwent surgery, and 51 underwent definitive (n = 29) or postoperative (n = 22) radiotherapy (RT). Median follow-up was 62 months. RESULTS: Median time to locoregional relapse was 14 months. Local failure was observed in 3 of 23 patients (13%) treated with surgery with or without postoperative RT vs. in 19 of 33 patients (56%) given organ-sparing treatment (p = 0.0008). Of 22 local failures, 16 (73%) were salvaged with surgery. Of the 33 patients treated with definitive RT (n = 29) and the 4 patients refusing RT after excisional biopsy, local control was obtained with organ preservation in 13 (39%). In the remaining 20, 4 patients with local failure underwent salvage conservatively, resulting in an ultimate penis preservation rate of 17 of 33 (52%) patients treated with definitive RT. The 5-year and 10-year probability of surviving with an intact penis was 43% and 26%, respectively. There was no survival difference between the patients treated with definitive RT and primary surgery (56% vs. 53%; p = 0.16). In multivariate analysis, independent factors influencing survival were N-classification and pathologic grade. Surgery was the only independent predictor for better local control. CONCLUSION: Based on our study findings, in patients with penile cancer, local control is superior with surgery. However, there is no difference in survival between patients treated with surgery and those treated with definitive RT, with 52% organ preservation.

Smooth muscle differentiation identifies two classes of poorly differentiated pleomorphic sarcomas with distinct outcome.

The clinical relevance of accurately diagnosing pleomorphic sarcomas has been shown, especially in cases of undifferentiated pleomorphic sarcomas with myogenic differentiation, which appear significantly more aggressive. To establish a new smooth muscle differentiation classification and to test its prognostic value, 412 sarcomas with complex genetics were examined by immunohistochemistry using four smooth muscle markers (calponin, h-caldesmon, transgelin and smooth muscle actin). Two tumor categories were first defined: tumors with positivity for all four markers and tumors with no or incomplete phenotypes. Multivariate analysis demonstrated that this classification method exhibited the strongest prognostic value compared with other prognostic factors, including histological classification. Secondly, incomplete or absent smooth muscle phenotype tumor group was then divided into subgroups by summing for each tumor the labeling intensities of all four markers for each tumors. A subgroup of tumors with an incomplete but strong smooth muscle differentiation phenotype presenting an intermediate metastatic risk was thus identified. Collectively, our results show that the smooth muscle differentiation classification method may be a useful diagnostic tool as well as a relevant prognostic tool for undifferentiated pleomorphic sarcomas.

Epiphysenfugenverletzungen der distalen Tibia. Sinnvolle Mehrinformation durch die MRT? [Epiphyseal injuries of the distal tibia. Does MRI provide useful additional information?]

Plain film radiography often underestimates the extent of injury in children with epiphyseal fracture. Especially Salter-Harris V fractures (crush fracture of the epiphyseal plate) are often primarily not detected. MRI of the ankle was performed in 10 children aged 9-17 (mean 14) years with suspected epiphyseal injury using 1.0-T Magnetom Expert. The fractures were classified according to the Salter-Harris-Rang-Odgen classification and compared with the results of plain radiography. In one case MRI could exclude epiphyseal injury; in four cases the MRI findings changed the therapeutic management. The visualisation of the fracture in three orthogonal planes and the possibility of detection of cartilage and ligamentous injury in MR imaging makes this method superior to conventional radiography and CT. With respect to radiation exposure MRI instead of CT should be used for the diagnosis of epiphyseal injuries in children.

Comprehensive molecular profiling of lung adenocarcinoma.

Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.

Association of ischaemic stroke subtype with long-term cardiovascular events.

BACKGROUND AND PURPOSE: There is no strong evidence that all ischaemic stroke types are associated with high cardiovascular risk. Our aim was to investigate whether all ischaemic stroke types are associated with high cardiovascular risk. METHODS: All consecutive patients with ischaemic stroke registered in the Athens Stroke Registry between 1 January 1993 and 31 December 2010 were categorized according to the TOAST classification and were followed up for up to 10 years. Outcomes assessed were cardiovascular and all-cause mortality, myocardial infarction, stroke recurrence, and a composite cardiovascular outcome consisting of myocardial infarction, angina pectoris, acute heart failure, sudden cardiac death, stroke recurrence and aortic aneurysm rupture. The Kaplan-Meier product limit method was used to estimate the probability of each end-point in each patient group. Cox proportional hazards models were used to determine the independent covariates of each end-point. RESULTS: Two thousand seven hundred and thirty patients were followed up for 48.1 ± 41.9 months. The cumulative probabilities of 10-year cardiovascular mortality in patients with cardioembolic stroke [46.6%, 95% confidence interval (CI) 40.6-52.8], lacunar stroke (22.1%, 95% CI 16.2-28.0) or undetermined stroke (35.2%, 95% CI 27.8-42.6) were either similar to or higher than those of patients with large-artery atherosclerotic stroke (LAA) (28.7%, 95% CI 22.4-35.0). Compared with LAA, all other TOAST types had a higher probability of 10-year stroke recurrence. In Cox proportional hazards analysis, compared with patients with LAA, patients with any other stroke type were associated with similar or higher risk for the outcomes of overall mortality, cardiovascular mortality, stroke recurrence and composite cardiovascular outcome. CONCLUSIONS: Large-artery atherosclerotic stroke and cardioembolic stroke are associated with the highest risk for future cardiovascular events, with the latter carrying at least as high a risk as LAA stroke.

Allergo-immunologie : 1. Dans quelles situations doit-on penser au syndrome des antiphospholipides? [When should consider antiphospholipid syndrome?]

En pratique courante, les événements thrombotiques ne sont pas rares. Dans le suivi des grossesses, les gynécologues ont souvent affaire à des pertes foetles chez leurs patientes. Jusqu'à quel point ces événements peuvent-ils être considérés comme "banals" ? Quand et sur quels critères doit-on considérer la possibilité d'un syndrome des antiphospholipides ? Des efforts ont été réalisés ces dernières années en vue de mieux codifier ce syndrome, tant sur le plan du laboratoire, que clinique. En vue d'uniformiser ces éléments, une première conférence de consensus a eu lieu en 1999 à Sapporo, avec mise à jour en 2004 à Sydney. Ces quelques lignes font le point sur les éléments nouveaux liés à la classification actuelle et sur les éléments diagnostiques en découlant, en vue de retenir le diagnostic de syndrome des antiphospholipides de manière rigoureuse, et d'initier le traitement adéquat dans les différentes situations liées à ce syndrome. In current practice, the occurrence of thrombosis--venous or arterial--is not rare. Moreover, during the follow-up of pregnancies, gynecologists often have to deal with fetal losses of their patients. Up to which point can these events be considered as "ordinary"? When and on which criteria can we consider an antiphospholipid syndrome? Efforts have been put these last years to better codify the diagnosis of this syndrome, so much on the laboratory side as on the clinical side. With a view to standardize these elements, a first consensus conference took place in 1999 in Sapporo, with an update in 2004 in Sydney, that has recently been published. The goal of these lines is to focus on new elements connected to the actual classification and on the resulting diagnosis elements, with the aim of obtaining a diagnosis of antiphospholipid syndrome in a rigorous way, and to initiate the appropriate treatment in different situations linked to this syndrome

A Small World Perspective on Urban Systems

The theory of small-world networks as initiated by Watts and Strogatz (1998) has drawn new insights in spatial analysis as well as systems theory. The theoryâeuro?s concepts and methods are particularly relevant to geography, where spatial interaction is mainstream and where interactions can be described and studied using large numbers of exchanges or similarity matrices. Networks are organized through direct links or by indirect paths, inducing topological proximities that simultaneously involve spatial, social, cultural or organizational dimensions. Network synergies build over similarities and are fed by complementarities between or inside cities, with the two effects potentially amplifying each other according to the âeurooepreferential attachmentâeuro hypothesis that has been explored in a number of different scientific fields (Barabási, Albert 1999; Barabási A-L 2002; Newman M, Watts D, Barabàsi A-L). In fact, according to Barabási and Albert (1999), the high level of hierarchy observed in âeurooescale-free networksâeuro results from âeurooepreferential attachmentâeuro, which characterizes the development of networks: new connections appear preferentially close to nodes that already have the largest number of connections because in this way, the improvement in the network accessibility of the new connection will likely be greater. However, at the same time, network regions gathering dense and numerous weak links (Granovetter, 1985) or network entities acting as bridges between several components (Burt 2005) offer a higher capacity for urban communities to benefit from opportunities and create future synergies. Several methodologies have been suggested to identify such denser and more coherent regions (also called communities or clusters) in terms of links (Watts, Strogatz 1998; Watts 1999; Barabási, Albert 1999; Barabási 2002; Auber 2003; Newman 2006). These communities not only possess a high level of dependency among their member entities but also show a low level of âeurooevulnerabilityâeuro, allowing for numerous redundancies (Burt 2000; Burt 2005). The SPANGEO project 2005âeuro"2008 (SPAtial Networks in GEOgraphy), gathering a team of geographers and computer scientists, has included empirical studies to survey concepts and measures developed in other related fields, such as physics, sociology and communication science. The relevancy and potential interpretation of weighted or non-weighted measures on edges and nodes were examined and analyzed at different scales (intra-urban, inter-urban or both). New classification and clustering schemes based on the relative local density of subgraphs were developed. The present article describes how these notions and methods contribute on a conceptual level, in terms of measures, delineations, explanatory analyses and visualization of geographical phenomena.

Being Female: a handicap for researchers in the competion for NCCR.

The Swiss National Science Foundation made a call for National Centers fo Competence in Research (NCCR) for the first time in 1999 and 2004. Together, these announcements concerned all disciplines and led to 126 preproposals, which were put forward by 2134 men and women researchers. It can be assumed that this operation mobilised Swiss researchers who regarded themselves as particularly well qualified to conduct high-level research in their field. The article uses network analysis and regression analysis methods to examine to what extend women had a lower success rate than men in the two selection rounds because of their sex. On the whole, the findings attest the gender neutrality of the National Science Foundation's selection procedures. However, they also confirm the well-known fact that women scientists are less represented in the higher echelons of academia and concentrated in the social sciences and humanities, as well as showing that this concentration reduces women's chances of success in scientific competition. The article shows that unequal gender-specific success rates prior to the NCCR funding contest play a fairly significant role.

A pipeline approach with spatial information for segmenting multiple sclerosis lesions on brain magnetic resonance imaging

Background: Conventional magnetic resonance imaging (MRI) techniques are highly sensitive to detect multiple sclerosis (MS) plaques, enabling a quantitative assessment of inflammatory activity and lesion load. In quantitative analyses of focal lesions, manual or semi-automated segmentations have been widely used to compute the total number of lesions and the total lesion volume. These techniques, however, are both challenging and time-consuming, being also prone to intra-observer and inter-observer variability.Aim: To develop an automated approach to segment brain tissues and MS lesions from brain MRI images. The goal is to reduce the user interaction and to provide an objective tool that eliminates the inter- and intra-observer variability.Methods: Based on the recent methods developed by Souplet et al. and de Boer et al., we propose a novel pipeline which includes the following steps: bias correction, skull stripping, atlas registration, tissue classification, and lesion segmentation. After the initial pre-processing steps, a MRI scan is automatically segmented into 4 classes: white matter (WM), grey matter (GM), cerebrospinal fluid (CSF) and partial volume. An expectation maximisation method which fits a multivariate Gaussian mixture model to T1-w, T2-w and PD-w images is used for this purpose. Based on the obtained tissue masks and using the estimated GM mean and variance, we apply an intensity threshold to the FLAIR image, which provides the lesion segmentation. With the aim of improving this initial result, spatial information coming from the neighbouring tissue labels is used to refine the final lesion segmentation.Results:The experimental evaluation was performed using real data sets of 1.5T and the corresponding ground truth annotations provided by expert radiologists. The following values were obtained: 64% of true positive (TP) fraction, 80% of false positive (FP) fraction, and an average surface distance of 7.89 mm. The results of our approach were quantitatively compared to our implementations of the works of Souplet et al. and de Boer et al., obtaining higher TP and lower FP values.Conclusion: Promising MS lesion segmentation results have been obtained in terms of TP. However, the high number of FP which is still a well-known problem of all the automated MS lesion segmentation approaches has to be improved in order to use them for the standard clinical practice. Our future work will focus on tackling this issue.

Development of a harmonised method for the profiling of amphetamine

Résumé : Cette thèse de doctorat est le fruit d'un projet de recherche européen financé par le quatrième programme cadre de la Commission Européenne (DG XII, Standards, Measurement and Testing). Ce projet, dénommé SMT-CT98-2277, a été financé pour la partie suisse par l'Office Fédéral de l'Education et de la Science (OFES, Berne, Suisse). Le but de ce projet était de développer une méthode harmonisée et collaborativement testée pour le profilage des impuretés de l'amphétamine illicite par chromatographie capillaire en phase gazeuse. Le travail a été divisé en sept phases majeures qui concernaient la synthèse de l'amphétamine, l'identification d'impuretés, l'optimisation de la préparation de l'échantillon et du système chromatographique, la variabilité des résultats, l'investigation de méthodes mathématiques pour la classification et la comparaison de profils et finalement l'application de la méthode à des réels échantillons illicites. La méthode résultant de ce travail n'a pas seulement montré que les données étaient interchangeables entre laboratoires mais aussi qu'elle était supérieure en de nombreux points aux méthodes préalablement publiées dans la littérature scientifique. Abstract : This Ph.D. thesis was carried out in parallel to an European project funded by the fourth framework program of the European Commission (DG XII, Standards, Measurement and Testing). This project, named SMT-CT98-2277 was funded, for the Swiss part, by the Federal Office of Education and Science (OFES, Bern, Switzerland). The aim of the project was to develop a harmonised, collaboratively tested method for the impurity profiling of illicit amphetamine by capillary gas chromatography. The work was divided into seven main tasks which deal with the synthesis of amphetamine, identification of impurities, optimization of sample preparation and of the chromatographic system, variability of the results, investigation of numerical methods for the classification and comparison of profiles and finally application of the methodology to real illicit samples. The resulting method has not only shown to produce interchangeable data between different laboratories but was also found to be superior in many aspects to previously published methods.

Modulation of genetic associations with serum urate levels by body-mass-index in humans.

We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, Pinter= 2.6 x 10-8). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDARADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10-8), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10-8), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10-4). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment.

Particularités du variant logopénique au sein des aphasies progressives primaires [Specificities of the logopenic variant of primary progressive aphasia].

The logopenic variant of primary progressive aphasia is a syndrome with neuropsychological and linguistic specificities, including phonological loop impairment for which diagnosis is currently mainly based on the exclusion of the two other variants, semantic and nonfluent/agrammatic primary progressive aphasia. The syndrome may be underdiagnosed due (1) to mild language difficulties during the early stages of the disease or (2) to being mistaken for mild cognitive impairment or Alzheimer's disease when the evaluation of episodic memory is based on verbal material and (3) finally, it is not uncommon that the disorders are attributed to psychiatric co-morbidities such as, for example, anxiety. Moreover, compared to other variants of primary progressive aphasia, brain abnormalities are different. The left temporoparietal junction is initially affected. Neuropathology and biomarkers (cerebrospinal fluid, molecular amyloid nuclear imaging) frequently reveal Alzheimer's disease. Consequently this variant of primary progressive aphasia does not fall under the traditional concept of frontotemporal lobar degeneration. These distinctive features highlight the utility of correct diagnosis, classification, and use of biomarkers to show the neuropathological processes underlying logopenic primary progressive aphasia. The logopenic variant of primary progressive aphasia is a specific form of Alzheimer's disease frequently presenting a rapid decline; specific linguistic therapies are needed. Further investigation of this syndrome is needed to refine screening, improve diagnostic criteria and better understand the epidemiology and the biological mechanisms involved.

Treatment of Prosthetic Joint Infections

Prosthetic joint replacement is one of the most successful surgical procedures of the last century and the number of implanted artificial joints is rapidly growing. While the result of the procedure is generally positive, infections may occur leading to patient suffering, surgeon's frustration and important costs to the health system. Infection after prosthetic joint replacement is thus a feared complication as healing rates can be low, functional result poor and satisfaction of the patient abysmal. However, if a patient-adapted treatment of infected total joints is used, an overall success rate of above 90 % can be obtained. The patient-adapted treatment concept is based on five strong pillars: teamwork, understanding biofilm, proper diagnostics, proper definition and classification and patient-tailored treatment.

La performance sportive comme travail

Au cours des dernières décennies, les recherches articulant sport et travail se sont beaucoup développées. Elles portent sur un large ensemble de questions comme le fonctionnement des organisations sportives, les carrières des sportifs de haut niveau, la croissance d'un secteur économique et de métiers de l'intervention sportive, les migrations internationales des sportifs, les discriminations sexuelles ou raciales dans l'accès aux marchés du travail sportif, etc. Ici nous mettons l'accent sur une dimension, centrale, des activités sportives : la compétition. Et notre objectif est d'analyser les mécanismes de production de la performance sportive. Nous considérons celle-ci comme le résultat d'un travail qui n'engage pas les seuls sportifs, avec leurs aptitudes, qualités ou capacités individuelles. Nous la définissons comme une activité collective, qui mobilise une pluralité d'acteurs, institutions, organisations. À travers une variété d'opérations de jugement, d'évaluation, de reconnaissance, de qualification, de cotation, de sélection, ces acteurs contribuent, de manière directe et décisive, à produire la performance sportive. En présentant des travaux empiriques qui argumentent cette problématique et la mobilisent dans des domaines variés (cyclisme, rugby, judo, etc.), nous invitons au développement de recherches sur le travail sportif. In recent decades, there has been much development in research connecting sport and work. It covers a wide range of questions such as how sports organisations operate, the careers of top-level athletes, the growth of an economic sector and its specific jobs, the international migrations of athletes, sexual or racial discrimination in access to the labour market in sport, etc. Here, we place the emphasis on one central dimension of sports activities : competition. Our objective is to analyse the mechanisms of production of sports performance. We consider this to be the outcome of work that does not only involve athletes, with their individual skills, qualities or capacities. We define it as a collective activity that marshals multiple actors, institutions, organisations. Through a variety of activities of judgement, evaluation, recognition, qualification, classification and selection, these actors contribute directly and decisively to producing sports performance. By presenting empirical work that discusses this issue and applies it in varied domains (cycling, rugby, judo, etc.), we call for the development of research into work in sport.