Predictors of the Indefinite-Duration Anticoagulation Treatment Strategy In Patients with Cancer Associated Thrombosis

Background: In patients with cancer and acute venous thromboembolism (VTE), current consensus guidelines recommend anticoagulation therapy for an indefinite duration or until the cancer is resolved. Methods and results: Among 1'247 patients with acute VTE enrolled in the Swiss Venous Thromboembolism Registry (SWIVTER) from 18 hospitals, 315 (25%) had cancer of whom 179 (57%) had metastatic disease, 159 (50%) ongoing or recent chemotherapy, and 83 (26%) tumor surgery within 6 months. Patients with cancer were older (66��14 vs. 60��19 years, p<0.001), more often hospitalized at the time of VTE diagnosis (46% vs. 36%, p=0.001), immobile for >3 days (25% vs. 16%, p<0.001), and more often had thrombocytopenia (6% vs. 1%, p<0.001) than patients without cancer. The 30-day rate of VTE-related death or recurrent VTE was 9% in cancer patients vs. 4% in patients without cancer (p<0.001), and the rates of bleeding requiring medical attention were 5% in both groups (p=0.57). Cancer patients received indefinite-duration anticoagulation treatment more often than patients without cancer (47% vs. 19%, p<0.001), and LMWH mono-therapy during the initial 3 months was prescribed to 45% vs. 8%, p<0.001, respectively. Among patients with cancer, prior VTE (OR 4.0, 95%CI 2.0-8.0), metastatic disease (OR 3.0, 95%CI 1.7-5.2), outpatient status at the time of VTE diagnosis (OR 3.8, 95%CI 1.9-7.6), and inpatient treatment (OR 4.4, 95%CI 2.1-9.2) were independently associated with the prescription of indefinite-duration anticoagulation treatment. Conclusions: Less than half of the cancer patients with acute VTE received a prescription for indefinite-duration anticoagulation treatment. Recurrent VTE, metastatic cancer, outpatient VTE diagnosis, and VTE requiring hospitalization were associated with an increased use of this strategy.

Occupational exposure to diisononyl phthalate (DiNP) in polyvinyl chloride processing operations

PURPOSE: Diisononyl phthalate (DiNP) is primarily used as a plasticizer in polyvinyl chloride (PVC) materials. While information is available on general population exposure to DiNP, occupational exposure data are lacking. We present DiNP metabolite urinary concentrations in PVC processing workers, estimate DiNP daily intake for these workers, and compare worker estimates to other populations. METHODS: We assessed DiNP exposure in participants from two companies that manufactured PVC materials, a PVC film manufacturer (n��=��25) and a PVC custom compounder (n��=��12). A mid-shift and end-shift urine sample was collected from each participant and analyzed for the DiNP metabolite mono(carboxy-isooctyl) phthalate (MCiOP). Mixed models were used to assess the effect on MCiOP concentrations of a worker being assigned to (1) a task using DiNP and (2) a shift where DiNP was used. A simple pharmacokinetic model was used to estimate DiNP daily intake from the MCiOP concentrations. RESULTS: Creatinine-adjusted MCiOP urinary concentrations ranged from 0.42-80��μg/g in PVC film and from 1.11-13.4��μg/g in PVC compounding. PVC film participants who worked on a task using DiNP (n��=��7) had the highest MCiOP geometric mean (GM) end-shift concentration (25.2��μg/g), followed by participants who worked on a shift where DiNP was used (n��=��11) (17.7��μg/g) as compared to participants with no task (2.92��μg/g) or shift (2.08��μg/g) exposure to DiNP. The GM end-shift MCiOP concentration in PVC compounding participants (4.80��μg/g) was comparable to PVC film participants with no task or shift exposure to DiNP. Because no PVC compounding participants were assigned to tasks using DINP on the day sampled, DiNP exposure in this company may be underestimated. The highest DiNP intake estimate was 26��μg/kg/day. CONCLUSION: Occupational exposure to DiNP associated with PVC film manufacturing tasks were substantially higher (sixfold to tenfold) than adult general population exposures; however, all daily intake estimates were less than 25% of current United States or European acceptable or tolerable daily intake estimates. Further characterization of DiNP occupational exposures in other industries is recommended.

Computational Approach to the Study of Thermal Spin Crossover Phenomena

The key parameters associated to the thermally induced spin crossover process have been calculated for a series of Fe(II) complexes with mono-, bi-, and tridentate ligands. Combination of density functional theory calculations for the geometries and for normal vibrational modes, and highly correlated wave function methods for the energies, allows us to accurately compute the entropy variation associated to the spin transition and the zero-point corrected energy difference between the low- and high-spin states. From these values, the transition temperature, T 1/2, is estimated for different compounds.

Comportamento de porta-enxertos de mangueira (Mangifera indica L.) submetidos a condi����es de baixas temperaturas

Neste experimento, observou-se o comportamento de porta-enxertos mono e poliembri��nicos de manga em rela����o a baixa temperaturas, na Esta����o Experimental de Agronomia de Tatu��, do IAC. Utilizaram-se como porta-enxertos monoembri��nicos as variedades Sensation, Haden e Tommy Atkins para a copa Haden, e os poliembri��nicos Coquinho, Manga-d'��gua, Carabao e Pico para as copas Haden e IAC 100 Bourbon. As mudas, com 18 a 24 meses de idade, foram plantadas em janeiro de 1990. As temperaturas registradas no abrigo meteorol��gico atingiram valores de 1��C, 2��C e 2,4��C, respectivamente, nos dias 19, 20 e 23 de maio de 1990; 1,6��C, 1��C e 2��C, nos dias 22, 23 e 24 de junho e 1��C e 2,4��C, nos dias 30 e 31 de julho, respectivamente. Essas temperaturas, no abrigo meteorol��gico, correspondem a temperaturas inferiores a 0��C ao n��vel do solo. Verificou-se que n��o houve morte do porta-enxerto Carabao, independentemente da copa enxertada. Para os demais porta-enxertos, o ��ndice de mortalidade variou de 35 a 70%.

Divergent and narrower climatic niches characterize polyploid species of European primroses in Primula sect. Aleuritia

Aim It is hypothesized that the ecological niches of polyploids should be both distinct and broader than those of diploids - characteristics that might have allowed the successful colonization of open habitats by polyploids during the Pleistocene glacial cycles. Here, we test these hypotheses by quantifying and comparing the ecological niches and niche breadths of a group of European primroses. Location Europe. Methods We gathered georeferenced data of four related species in Primula sect. Aleuritia at different ploidy levels (diploid, tetraploid, hexaploid and octoploid) and used seven bioclimatic variables to quantify niche overlap between species by applying a series of univariate and multivariate analyses combined with modelling techniques. We also employed permutation-based tests to evaluate niche similarity between the four species. Niche breadth for each species was evaluated both in the multivariate environmental space and in geographical space. Results The four species differed significantly from each other in mono-dimensional comparisons of climatological variables and occupied distinct habitats in the multi-dimensional environmental space. The majority of the permutation-based tests either indicated that the four species differed significantly in their habitat preferences and ecological niches or did not support significant niche similarity. Furthermore, our results revealed narrower niche breadths and geographical ranges in species of P. sect. Aleuritia at higher ploidy levels. Main conclusions The detected ecological differentiation between the four species of P. sect. Aleuritia at different ploidy levels is consistent with the hypothesis that polyploids occupy distinct ecological niches that differ from those of their diploid relative. Contrary to expectations, we find that polyploid species of P. sect. Aleuritia occupy narrower environmental and geographical spaces than their diploid relative. These results on the ecological niches of closely related polyploid and diploid species highlight factors that potentially contribute to the evolution and distribution of polyploid species.

Artificial evolution on network structures : how time and space influence dynamics

Abstract The main objective of this work is to show how the choice of the temporal dimension and of the spatial structure of the population influences an artificial evolutionary process. In the field of Artificial Evolution we can observe a common trend in synchronously evolv��ing panmictic populations, i.e., populations in which any individual can be recombined with any other individual. Already in the '90s, the works of Spiessens and Manderick, Sarma and De Jong, and Gorges-Schleuter have pointed out that, if a population is struc��tured according to a mono- or bi-dimensional regular lattice, the evolutionary process shows a different dynamic with respect to the panmictic case. In particular, Sarma and De Jong have studied the selection pressure (i.e., the diffusion of a best individual when the only selection operator is active) induced by a regular bi-dimensional structure of the population, proposing a logistic modeling of the selection pressure curves. This model supposes that the diffusion of a best individual in a population follows an exponential law. We show that such a model is inadequate to describe the process, since the growth speed must be quadratic or sub-quadratic in the case of a bi-dimensional regular lattice. New linear and sub-quadratic models are proposed for modeling the selection pressure curves in, respectively, mono- and bi-dimensional regu��lar structures. These models are extended to describe the process when asynchronous evolutions are employed. Different dynamics of the populations imply different search strategies of the resulting algorithm, when the evolutionary process is used to solve optimisation problems. A benchmark of both discrete and continuous test problems is used to study the search characteristics of the different topologies and updates of the populations. In the last decade, the pioneering studies of Watts and Strogatz have shown that most real networks, both in the biological and sociological worlds as well as in man-made structures, have mathematical properties that set them apart from regular and random structures. In particular, they introduced the concepts of small-world graphs, and they showed that this new family of structures has interesting computing capabilities. Populations structured according to these new topologies are proposed, and their evolutionary dynamics are studied and modeled. We also propose asynchronous evolutions for these structures, and the resulting evolutionary behaviors are investigated. Many man-made networks have grown, and are still growing incrementally, and explanations have been proposed for their actual shape, such as Albert and Barabasi's preferential attachment growth rule. However, many actual networks seem to have undergone some kind of Darwinian variation and selection. Thus, how these networks might have come to be selected is an interesting yet unanswered question. In the last part of this work, we show how a simple evolutionary algorithm can enable the emrgence o these kinds of structures for two prototypical problems of the automata networks world, the majority classification and the synchronisation problems. Synopsis L'objectif principal de ce travail est de montrer l'influence du choix de la dimension temporelle et de la structure spatiale d'une population sur un processus ��volutionnaire artificiel. Dans le domaine de l'Evolution Artificielle on peut observer une tendence �� ��voluer d'une fa��on synchrone des populations panmictiques, o�� chaque individu peut ��tre r��combin�� avec tout autre individu dans la population. D��j�� dans les ann��e '90, Spiessens et Manderick, Sarma et De Jong, et Gorges-Schleuter ont observ�� que, si une population poss��de une structure r��guli��re mono- ou bi-dimensionnelle, le processus ��volutionnaire montre une dynamique diff��rente de celle d'une population panmictique. En particulier, Sarma et De Jong ont ��tudi�� la pression de s��lection (c-��-d la diffusion d'un individu optimal quand seul l'op��rateur de s��lection est actif) induite par une structure r��guli��re bi-dimensionnelle de la population, proposant une mod��lisation logistique des courbes de pression de s��lection. Ce mod��le suppose que la diffusion d'un individu optimal suit une loi exponentielle. On montre que ce mod��le est inad��quat pour d��crire ce ph��nom��ne, ��tant donn�� que la vitesse de croissance doit ob��ir �� une loi quadratique ou sous-quadratique dans le cas d'une structure r��guli��re bi-dimensionnelle. De nouveaux mod��les lin��aires et sous-quadratique sont propos��s pour des structures mono- et bi-dimensionnelles. Ces mod��les sont ��tendus pour d��crire des processus ��volutionnaires asynchrones. Diff��rentes dynamiques de la population impliquent strategies diff��rentes de recherche de l'algorithme r��sultant lorsque le processus ��volutionnaire est utilis�� pour r��soudre des probl��mes d'optimisation. Un ensemble de probl��mes discrets et continus est utilis�� pour ��tudier les charact��ristiques de recherche des diff��rentes topologies et mises �� jour des populations. Ces derni��res ann��es, les ��tudes de Watts et Strogatz ont montr�� que beaucoup de r��seaux, aussi bien dans les mondes biologiques et sociologiques que dans les structures produites par l'homme, ont des propri��t��s math��matiques qui les s��parent �� la fois des structures r��guli��res et des structures al��atoires. En particulier, ils ont introduit la notion de graphe sm,all-world et ont montr�� que cette nouvelle famille de structures poss��de des int��ressantes propri��t��s dynamiques. Des populations ayant ces nouvelles topologies sont propos��s, et leurs dynamiques ��volutionnaires sont ��tudi��es et mod��lis��es. Pour des populations ayant ces structures, des m��thodes d'��volution asynchrone sont propos��es, et la dynamique r��sultante est ��tudi��e. Beaucoup de r��seaux produits par l'homme se sont form��s d'une fa��on incr��mentale, et des explications pour leur forme actuelle ont ��t�� propos��es, comme le preferential attachment de Albert et Barab��si. Toutefois, beaucoup de r��seaux existants doivent ��tre le produit d'un processus de variation et s��lection darwiniennes. Ainsi, la fa��on dont ces structures ont pu ��tre s��lectionn��es est une question int��ressante rest��e sans r��ponse. Dans la derni��re partie de ce travail, on montre comment un simple processus ��volutif artificiel permet �� ce type de topologies d'��merger dans le cas de deux probl��mes prototypiques des r��seaux d'automates, les t��ches de densit�� et de synchronisation.

Utilizaci��n de an��logos fluorados de la feromona sexual de Sesamia nonagrioides Lef. como inhibidores de su actividad biol��gica

Se ha estudiado el papel, como inhibidores de la acci��n feromonal, de determinados fluoroderivados, an��logos estructurales del acetato de (Z)-l 1-hexadecenilo, componente principal de la feromona sexual del noctuido Sesamia nonagrioides Lef. Dichos compuestos fueron los an��logos fluoroacetato (mono, di y trifluoroacetato de (Z)-l 1-hexadecenilo) y la trifluorometilcetona an��loga [(Z)-1,1,1 -trifluoro-14-nonadecen-2-ona]. La acci��n inhibidora fue evaluada a partir de los resultados de actividad electrofisiol��gica (pruebas de electroantenograma, EAG), de estudios de comportamiento en pruebas de t��nel de viento y de pruebas de capturas en campo. Los acetatos fluorados, especialmente el mono y el trifluoracetato, se mostraron como buenos inhibidores de la acci��n atrayente de la feromona en los tres tipos de pruebas realizadas, mientras que la trifluorometilcetona an��loga mostr�� una actividad mucho menor.

Identifica����o de microssat��lites para o mamoeiro por meio da explora����o do banco de dados de DNA

Os marcadores microssat��lites s��o ferramentas ��teis em diversas an��lises gen��ticas em plantas. No caso do mamoeiro (Carica papaya L.), poucos locos de microssat��lites foram descritos at�� o momento. Assim, o objetivo deste trabalho foi explorar a base de dados do GenBank / NCBI (National Center of Biotechnoloy Information) �� procura de microssat��lites de mamoeiro, visando a seu futuro uso em estudos gen��ticos e moleculares aplicados ao melhoramento gen��tico. As seq����ncias foram obtidas no GenBank / NCBI, no formato FASTA, e analisadas para a presen��a de microssat��lites com um m��nimo de 20; 7 e 5 repeti����es dos motivos de mono-, di- e trinucleot��deos, respectivamente, e acima de 4 repeti����es para tetra- e pentanucleot��deos. Seq����ncias com mais de 90% de similaridade foram consideradas redundantes e, portanto, eliminadas das an��lises. Foram analisadas 44.591 seq����ncias, das quais 3.180 foram n��o-redundantes e apresentaram 3.947 microssat��lites. Desse total, 3.587 foram classificados como microssat��lites perfeitos, 8 imperfeitos, 65 interrompidos, 239 compostos-perfeitos, 8 compostos-imperfeitos e 40 compostos-interrompidos. As repeti����es de di- e trinucleot��deos representaram 65,7 e 14,4% do total de seq����ncias analisadas, respectivamente. Somente os motivos do tipo AT/TA representaram 44,1% dos microssat��lites encontrados. Os motivos mais comuns de tri-, tetra- e pentanucleot��deos foram AAT, AATT e TTTAA, respectivamente. Observou-se que, nas seq����ncias dispon��veis, o genoma do mamoeiro apresenta, em m��dia, um microssat��lite a cada 5,65 kb.

Characterization of hepatic fatty acids in mice with reduced liver fat by ultra-short echo time (1)H-MRS at 14.1 T in vivo.

Alterations in the hepatic lipid content (HLC) and fatty acid composition are associated with disruptions in whole body metabolism, both in humans and in rodent models, and can be non-invasively assessed by (1)H-MRS in vivo. We used (1)H-MRS to characterize the hepatic fatty-acyl chains of healthy mice and to follow changes caused by streptozotocin (STZ) injection. Using STEAM at 14.1 T with an ultra-short TE of 2.8 ms, confounding effects from T2 relaxation and J-coupling were avoided, allowing for accurate estimations of the contribution of unsaturated (UFA), saturated (SFA), mono-unsaturated (MUFA) and poly-unsaturated (PUFA) fatty-acyl chains, number of double bonds, PU bonds and mean chain length. Compared with in vivo (1) H-MRS, high resolution NMR performed in vitro in hepatic lipid extracts reported longer fatty-acyl chains (18 versus 15 carbons) with a lower contribution from UFA (61 �� 1% versus 80 �� 5%) but a higher number of PU bonds per UFA (1.39 �� 0.03 versus 0.58 �� 0.08), driven by the presence of membrane species in the extracts. STZ injection caused a decrease of HLC (from 1.7 �� 0.3% to 0.7 �� 0.1%), an increase in the contribution of SFA (from 21 �� 2% to 45 �� 6%) and a reduction of the mean length (from 15 to 13 carbons) of cytosolic fatty-acyl chains. In addition, SFAs were also likely to have increased in membrane lipids of STZ-induced diabetic mice, along with a decrease of the mean chain length. These studies show the applicability of (1)H-MRS in vivo to monitor changes in the composition of the hepatic fatty-acyl chains in mice even when they exhibit reduced HLC, pointing to the value of this methodology to evaluate lipid-lowering interventions in the scope of metabolic disorders.

Comparison of Inoculation with the InoqulA and WASP Automated Systems with Manual Inoculation.

The quality of sample inoculation is critical for achieving an optimal yield of discrete colonies in both monomicrobial and polymicrobial samples to perform identification and antibiotic susceptibility testing. Consequently, we compared the performance between the InoqulA (BD Kiestra), the WASP (Copan), and manual inoculation methods. Defined mono- and polymicrobial samples of 4 bacterial species and cloudy urine specimens were inoculated on chromogenic agar by the InoqulA, the WASP, and manual methods. Images taken with ImagA (BD Kiestra) were analyzed with the VisionLab version 3.43 image analysis software to assess the quality of growth and to prevent subjective interpretation of the data. A 3- to 10-fold higher yield of discrete colonies was observed following automated inoculation with both the InoqulA and WASP systems than that with manual inoculation. The difference in performance between automated and manual inoculation was mainly observed at concentrations of >10(6) bacteria/ml. Inoculation with the InoqulA system allowed us to obtain significantly more discrete colonies than the WASP system at concentrations of >10(7) bacteria/ml. However, the level of difference observed was bacterial species dependent. Discrete colonies of bacteria present in 100- to 1,000-fold lower concentrations than the most concentrated populations in defined polymicrobial samples were not reproducibly recovered, even with the automated systems. The analysis of cloudy urine specimens showed that InoqulA inoculation provided a statistically significantly higher number of discrete colonies than that with WASP and manual inoculation. Consequently, the automated InoqulA inoculation greatly decreased the requirement for bacterial subculture and thus resulted in a significant reduction in the time to results, laboratory workload, and laboratory costs.

Determinants of antithrombotic choice for patent foramen ovale in cryptogenic stroke.

OBJECTIVE: We examined the influence of clinical, radiologic, and echocardiographic characteristics on antithrombotic choice in patients with cryptogenic stroke (CS) and patent foramen ovale (PFO), hypothesizing that features suggestive of paradoxical embolism might lead to greater use of anticoagulation. METHODS: The Risk of Paradoxical Embolism Study combined 12 databases to create the largest dataset of patients with CS and known PFO status. We used generalized linear mixed models with a random effect of component study to explore whether anticoagulation was preferentially selected based on the following: (1) younger age and absence of vascular risk factors, (2) "high-risk" echocardiographic features, and (3) neuroradiologic findings. RESULTS: A total of 1,132 patients with CS and PFO treated with anticoagulation or antiplatelets were included. Overall, 438 participants (39%) were treated with anticoagulation with a range (by database) of 22% to 54%. Treatment choice was not influenced by age or vascular risk factors. However, neuroradiologic findings (superficial or multiple infarcts) and high-risk echocardiographic features (large shunts, shunt at rest, and septal hypermobility) were predictors of anticoagulation use. CONCLUSION: Both antithrombotic regimens are widely used for secondary stroke prevention in patients with CS and PFO. Radiologic and echocardiographic features were strongly associated with treatment choice, whereas conventional vascular risk factors were not. Prior observational studies are likely to be biased by confounding by indication.

Risk factors, aetiology and outcome of ischaemic stroke in young adults: the Swiss Young Stroke Study (SYSS).

Ischaemic stroke (IS) in young adults has been increasingly recognized as a serious health condition. Stroke aetiology is different in young adults than in the older population. This study aimed to investigate aetiology and risk factors, and to search for predictors of outcome and recurrence in young IS patients. We conducted a prospective multicentre study of consecutive IS patients aged 16-55��years. Baseline demographic data, risk factors, stroke aetiology including systematic genetic screening for Fabry disease and severity were assessed and related to functional neurological outcome (modified Rankin Scale, mRS), case fatality, employment status, place of residence, and recurrent cerebrovascular events at 3��months. In 624 IS patients (60��% men), median age was 46 (IQR 39-51) years and median NIHSS on admission 3 (IQR 1-8). Modifiable vascular risk factors were found in 73��%. Stroke aetiology was mostly cardioembolism (32��%) and of other defined origin (24��%), including cervicocerebral artery dissection (17��%). Fabry disease was diagnosed in 2 patients (0.3��%). Aetiology remained unknown in 20��%. Outcome at 3��months was favourable (mRS 0-1) in 61��% and fatal in 2.9��%. Stroke severity (p��<��0.001) and diabetes mellitus (p��=��0.023) predicted unfavourable outcome. Stroke recurrence rate at 3��months was 2.7��%. Previous stroke or TIA predicted recurrent cerebrovascular events (p��=��0.012). In conclusion, most young adults with IS had modifiable vascular risk factors, emphasizing the importance of prevention strategies. Outcome was unfavourable in more than a third of patients and was associated with initial stroke severity and diabetes mellitus. Previous cerebrovascular events predicted recurrent ones.

Dietary intake according to gender and education : a twenty-year trend in a Swiss adult population

We assessed trends in dietary intake according to gender and education using repeated cross-sectional, population-based surveys conducted between 1993 and 2012 in Geneva, Switzerland (17,263 participants, 52.0 �� 10.6 years, 48% male). In 1993-1999, higher educated men had higher monounsaturated fatty acids (MUFA), carotene and vitamin D intakes than lower educated men, and the differences decreased in 2006-2012. In 1993-1999, higher educated women had higher fiber, iron, carotene, vitamin D and alcohol intakes than lower educated women, and the differences decreased in 2006-2012. Total energy, polyunsaturated fatty acids, retinol and alcohol intakes decreased, while mono/disaccharides, MUFA and carotene intake increased in both genders. Lower educated men had stronger decreases in saturated fatty acid (SFA) and calcium intakes than higher educated men: multivariate-adjusted slope and 95% confidence interval -0.11 (-0.15; -0.06) vs. -0.03 (-0.08; 0.02) g/day/year for SFA and -5.2 (-7.8; -2.7) vs. -1.03 (-3.8; 1.8) mg/day/year for calcium, p for interaction <0.05. Higher educated women had a greater decrease in iron intake than lower educated women: -0.03 (-0.04; -0.02) vs. -0.01 (-0.02; 0.00) mg/day/year, p for interaction = 0.002. We conclude that, in Switzerland, dietary intake evolved similarly between 1993 and 2012 in both educational groups. Educational differences present in 1993 persisted in 2012.

Les bifurcations du r��cit interactif: continuit�� ou rupture?

Ainsi que l'affirmaient les premiers narratologues, le récit est une forme qui transcende les médias et si l'on peut reconnaître ses �� avatars �� jusque dans les jeux de r��le et les jeux vidéo, alors la confrontation entre narratologie et ludologie peut s'avérer une étape incontournable dans la refondation des concepts de la théorie du récit. Ainsi que l'affirmait récemment Werner Wolf : �� une approche intermédiale peut [...] contribuer à éviter les généralisations unilatérales que l'on a pu observer dans les recherches mono-médiales antérieures �� en particulier dans les travaux �� centrés sur les textes verbaux �� (Wolf 2003 : 193, n.t.). En retour, on peut espérer que ce recadrage conceptuel offre un point de vue nouveau sur les phénomènes narratifs, dont l'impact pourrait aller jusqu'à transformer notre appréhension des romans de l'âge baroque jusqu'aux fictions télévisuelles qui dominent le paysage médiatique contemporain. Ce numéro des Cahiers de narratologie est issu d'une journée d'étude qui s'est tenue à l'Université de Lausanne (UNIL) le 14 février 2014. Cette journée était organisée par Raphaël Baroni, Marc Marti, Claire Clivaz et Frédéric Kaplan et elle a bénéficié du soutien de l'EFLE (UNIL), du LADHUL (UNIL), du LIRCES (Université de Nice Sophia Antipolis), du DHLAB (Ecole Polytechnique Fédérale de Lausanne) et du Réseau romand de narratologie.

Potential blindness in children of patients with hereditary bone disease.

Mono- and bi-allelic mutations in the low-density lipoprotein receptor related protein 5 (LRP5) may cause osteopetrosis, autosomal dominant and recessive exudative vitreoretinopathy, juvenile osteoporosis, or persistent hyperplastic primary vitreous (PHPV). We report on a child affected with PHPV and carrying compound mutations. The father carried the splice mutation and suffered from severe bone fragility since childhood. The mother carried the missense mutation without any clinical manifestations. The genetic diagnosis of their child allowed for appropriate treatment in the father and for the detection of osteopenia in the mother. Mono- and bi-allelic mutations in LRP5 may cause osteopetrosis, autosomal dominant and recessive exudative vitreoretinopathy, juvenile osteoporosis, or PHPV. PHPV is a component of persistent fetal vasculature of the eye, characterized by highly variable expressivity and resulting in a wide spectrum of anterior and/or posterior congenital developmental defects, which may lead to blindness. We evaluated a family diagnosed with PHPV in their only child. The child presented photophobia during the first 3��weeks of life, followed by leukocoria at 2��months of age. Molecular resequencing of NDP, FZD4, and LRP5 was performed in the child and segregation of the observed mutations in the parents. At presentation, fundus examination of the child showed a retrolental mass in the right eye. Ultrasonography revealed retinal detachment in both eyes. Thorough familial analysis revealed that the father suffered from many fractures since childhood without specific fragility bone diagnosis, treatment, or management. The mother was asymptomatic. Molecular analysis in the proband identified two mutations: a c.[2091+2T>C] splice mutation and c.[1682C>T] missense mutation. We report the case of a child affected with PHPV and carrying compound heterozygous LRP5 mutations. This genetic diagnosis allowed the clinical diagnosis of the bone problem to be made in the father, resulting in better management of the family. It also enabled preventive treatment to be prescribed for the mother and accurate genetic counseling to be provided.