U Simeoni

University Hospital of Lausanne, Lausanne, Vaud, Switzerland

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Publications (188)422.46 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Epigenetic changes have long-lasting effects on gene expression and are related to, and often induced by, the environment in which early development takes place. In particular, the period of development that extends from pre-conception to early infancy is the period of life during which epigenetic DNA imprinting activity is the most active. Epigenetic changes have been associated with modification of the risk for developing a wide range of adulthood, non-communicable diseases (including cardiovascular diseases, metabolic diseases, diseases of the reproductive system, etc.). This paper reviews the molecular basis of epigenetics, and addresses the issues related to the process of developmental programming of the various areas of human health. © 2014 Elsevier Ireland Ltd. All rights reserved.
    Early Human Development 09/2014; 90 Suppl 2:S23-4. · 2.02 Impact Factor
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    ABSTRACT: Recent studies have shown that a low birth weight is a risk factor for increased systemic blood pressure (BP) in adulthood. Further, systemic BP and arterial stiffness (AS) are reported to be increased in adolescents born prematurely. The purpose of this study was to characterize systemic BP and AS in young adults born preterm. Systemic BP was measured using an automated oscillometric device. AS was assessed by measuring the right carotid-radial pulse wave velocity (PWV) using a validated non-invasive automated method. Systemic BP, pulse pressure, and PWV [mean (confidence intervals)] were compared between 16 adults (age 21 years) born preterm (age at birth 32 weeks of gestation) with a birth weight (1710 g) appropriate for their gestational age and 15 adults (21 years) born at term (40 weeks of gestation) with a birth weight (3430 g) appropriate for their gestational age. Adults born preterm had a significantly higher systolic BP [122 mmHg (114-144) v. 112 (106-127)], mean BP [89 mmHg (86-98) v. 84 (81-91)], diastolic BP [69 mmHg (66-76) v. 65 (62-78)], pulse pressure [54 mmHg (47-72) v. 47 (42-60)], and PWV [7 m/s (6.3-8.6) v. 6.4 (5.8-8)] than did those born at term. Our findings suggest that young adults with a low birth weight due to preterm birth have increased systemic BP and AS. Accordingly, preterm birth may predispose individuals to cardiovascular diseases in adulthood due to increased AS.
    Journal of Developmental Origins of Health and Disease 08/2014; · 1.21 Impact Factor
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    ABSTRACT: In the 1980s, David Barker and Colleagues proposed that the major causes of cardiovascular and metabolic diseases have their roots in early development. There is now robust evidence that an hyperglycemic intrauterine environment is responsible not only for significant short-term morbidity in the fetus and the neonate but also for an increased risk of developing diabetes as well as other chronic, noncommunicable diseases at adulthood. The risk is higher in pregestational diabetes, but unrecognized and/or poorly managed gestational diabetes (GDM) may have similar consequences. Although a relatively clear picture of the pathogenesis of the fetal and neonatal complications of maternal diabetes and of their interrelationship is available today, the intimate molecular mechanisms involved in the long term are far from being understood. While the rate of GDM is sharply increasing in association with the pandemic of obesity and of type 2 diabetes over the world, we review here the current understanding of short- and long-term outcomes of fetuses exposed to a diabetic environment.
    Bailli&egrave re s Best Practice and Research in Clinical Obstetrics and Gynaecology 08/2014; · 2.02 Impact Factor
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    ABSTRACT: Abstract Background: After prenatal diagnosis of lethal fetal abnormality (LFA), some couples choose to continue the pregnancy rather than opt for termination of the pregnancy. This may result in the requirement for neonatal palliative care, which in France is prescribed by the Leonetti Law. These rare situations raise various questions about when and how palliative care is provided in cases of LFA. Objective: The main goal of the study was to clarify the place given to the concept of perinatal palliative care within the antenatal information provided by perinatal professionals. This work was specifically aimed at revealing caregivers' perceptions of and attitudes toward LFA, how it is managed, and procedures for decision making and providing information. Methods: This is a qualitative study using focus groups from two French Multidisciplinary Centers for Prenatal Diagnosis. All verbal production (individual statements, verbal exchanges, etc.) produced during the two focus groups was fully transcribed and the content analyzed. Results: Content analysis revealed four main themes: (1) defining LFA; (2) the source and nature of information about LFA and how it is communicated; (3) therapeutic options and decisions in the management of LFA; and (4) palliative care (limits and criteria) in the context of LFA. Conclusions: Consistency as regards the perceived intention of care among all members of the health care team is essential to support parents facing a possible fatal outcome. Attitudes and practices at Multidisciplinary Centers for Prenatal Diagnosis need to be shaped on a national basis.
    Journal of palliative medicine. 05/2014;
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    ABSTRACT: Lipids are an important source of energy for young children and play a major role in the development and functioning of nervous tissue. Essential fatty acids and their long-chain derivatives also fulfill multiple metabolic functions and play a role in the regulation of numerous genes. The Food and Agriculture Organization of the United Nations (FAO), the World Health Organization (WHO), and the French Agency for Food, Environmental and Occupational Health & Safety (Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail [ANSES]) have recently recommended a minimum daily intake in preformed long-chain polyunsaturated fatty acids (LC-PUFAs): arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Mother's milk remains the only reference, but the large variability in its DHA content does not guarantee that breastfed children receive an optimal DHA intake if the mother's intake is insufficient. For children fed with infant formulas, ARA and DHA intake is often below the recommended intake because only one-third of infant formulas available on the market in France are enriched in LC-PUFAs. For all children, linoleic acid (LA) intake is on average higher than the minimal recommended values. The consequences of these differences between intake and recommended values are uncertain. A cautious attitude is to come close to the current recommendations and to advise sufficient consumption of DHA in breastfeeding women. For bottle-fed children, infant formulas enriched in LC-PUFAs and with moderate levels of LA should be preferred. LC-PUFA-rich fish should be consumed during breastfeeding, and adapted vegetable oils when complementary foods are introduced.
    Archives de Pédiatrie 04/2014; 21(4):424-38. · 0.36 Impact Factor
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    ABSTRACT: Very early in life, sodium intake correlates with blood pressure level. This warrants limiting the consumption of sodium by children. However, evidence regarding exact sodium requirements in that age range is lacking. This article focuses on the desirable sodium intake according to age as suggested by various groups of experts, on the levels of sodium intake recorded in consumption surveys, and on the public health strategies implemented to reduce salt consumption in the pediatric population. Practical recommendations are given by the Committee on nutrition of the French Society of Pediatrics in order to limit salt intake in children.
    Archives de Pédiatrie 03/2014; · 0.36 Impact Factor
  • M Saint-Faust, F Boubred, U Simeoni
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    ABSTRACT: The structural and functional development of the kidney is responsible for a significant impact on postnatal adaptation to extrauterine life. Prenatal or neonatal impairment of nephrogenesis may carry long term, lifelong consequences in terms of reduced nephron endowment, chronic kidney disease, and cardiovascular risks at adulthood. Intrauterine growth restriction, preterm birth, congenital renal, and urinary tract anomalies are for long widely incriminated. Neonatal administration of nephrotoxic drugs has been associated with short-term acute kidney injury and longer chronic kidney disease. This review attempts at offering a comprehensive understanding of the renal development, the neonatal renal transition to extrauterine life and subsequent maturation phase during early infancy. It also focuses on developmental and maturational changes that impact lifelong renal function and adult health.
    American Journal of Perinatology 03/2014; · 1.57 Impact Factor
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    ABSTRACT: Background:Perinatal cerebral hypoxia-ischemia (HI) can lead to severe neurodevelopmental disorders. Studies in humans and in animal models mainly focused on cerebral outcomes and little is known about the mechanisms that may affect the brainstem and the spinal cord. Dysfunctions of neuromodulatory systems, such as the serotonergic (5-HT) projections, critical for the development of neural networks, have been postulated to underlie behavioral and motor deficits, as well as metabolic changes.Methods:The aim of this study was to investigate brainstem and spinal cord functions by means of plethysmography and sensorimotor tests in a neonatal Rice-Vanucci model of hypoxia-ischemia (HI) in mice. We also evaluated bioaminergic contents in central regions dedicated to the motor control of autonomic functions.Results:Mice with cerebral infarct expressed motor disturbances, had a lower body weight and a decreased respiratory frequency than SHAM suggesting defects of brainstem neural network involved in the motor control of feeding, suckling, swallowing and respiration. Moreover, our study revealed changes of monoamines and amino acids contents in the brainstem and the spinal cord of HI mice.Conclusions:Our results suggest that monoaminergic neuromodulation plays an important role in the physiopathology of HI brain injury that may represent a good therapeutic target.Pediatric Research (2014); doi:10.1038/pr.2014.42.
    Pediatric Research 03/2014; · 2.67 Impact Factor
  • U. Simeoni
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    ABSTRACT: La prematuridad, un importante desafío de salud pública, afecta al 7-14% de los nacimientos en todo el mundo. Aunque los considerables adelantos técnicos y científicos han hecho posible la supervivencia de niños cada vez más inmaduros, los casos más frecuentes se refieren a la prematuridad tardía. En condiciones de gran prematuridad (antes de las 33 semanas de amenorrea), el nacimiento se programa en un centro de nivel 3 y la madre es trasladada en el período prenatal. La asistencia médica es perinatal y se inicia con la corticoterapia prenatal para acelerar la maduración fetal ante una amenaza de parto prematuro. La estabilización en la sala de parto está relativamente exenta de dificultades. Sin embargo, una serie de complicaciones posibles en la unidad de reanimación neonatal puede alterar la estancia hospitalaria, con una mortalidad y morbilidad que por lo general son proporcionales al grado de inmadurez. Los cuidados se orientan hoy hacia una conducta menos agresiva, centrada en el desarrollo del niño de forma personalizada y con la estrecha cooperación de los padres. La etapa posthospitalaria y el seguimiento a largo plazo son claves para la calidad de la vida futura de estos niños, algunos de los cuales están expuestos a trastornos del desarrollo psicomotor e incluso a una mayor incidencia de enfermedades no transmisibles del adulto como la hipertensión arterial y la diabetes de tipo 2.
    EMC - Tratado de Medicina. 03/2014; 18(1):1–7.
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    ABSTRACT: Epidemiological and experimental studies indicate that early vascular dysfunction occurs in low birth weight subjects, especially preterm infants (PT). We recently reported impaired angiogenic activity of endothelial colony forming cells (ECFCs) in this condition. We hypothesized that ECFCs dysfunction in PT might result from premature senescence and investigated the underlying mechanisms. Compared to ECFCs from term neonates (n=18), ECFCs isolated from PT (n=29) display an accelerated senescence sustained by growth arrest and increased senescence-associated β-galactosidase activity. Increased p16(INK4a) expression, in the absence of telomere shortening, indicates that premature PT-ECFCs ageing results from stress-induced senescence. SIRT1 level, a NAD-dependent deacetylase with anti-aging activities, is dramatically decreased in PT-ECFCs and correlated with gestational age. SIRT1 deficiency is subsequent to epigenetic silencing of its promoter. Transient SIRT1 overexpression or chemical-induction by resveratrol treatment reverses senescence phenotype, and rescues in vitro PT-ECFCs angiogenic defect in a SIRT1-dependent manner. SIRT-1 overexpression also restores PT-ECFCs capacity for neovessel formation in vivo. We thus demonstrate that decreased expression of SIRT1 drives accelerated senescence of PT-ECFCs, and acts as a critical determinant of PT-ECFCs angiogenic defect. These findings lay news grounds for understanding the increased cardiovascular risk in individuals born prematurely and open perspectives for therapeutic strategy.
    Blood 02/2014; · 9.78 Impact Factor
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    ABSTRACT: Very early in life, sodium intake correlates with blood pressure level. This warrants limiting the consumption of sodium by children. However, evidence regarding exact sodium requirements in that age range is lacking. This article focuses on the desirable sodium intake according to age as suggested by various groups of experts, on the levels of sodium intake recorded in consumption surveys, and on the public health strategies implemented to reduce salt consumption in the pediatric population. Practical recommendations are given by the Committee on nutrition of the French Society of Pediatrics in order to limit salt intake in children.
    Archives de Pédiatrie. 01/2014;
  • The Journal of pediatrics 12/2013; · 4.02 Impact Factor
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    ABSTRACT: The prevalence of breastfeeding in France is one of the lowest in Europe: 65% of infants born in France in 2010 were breastfed when leaving the maternity ward. Exclusive breastfeeding allows normal growth until at least 6 months of age, and can be prolonged until the age of 2 years or more, provided that complementary feeding is started after 6 months. Breast milk contains hormones, growth factors, cytokines, immunocompetent cells, etc., and has many biological properties. The composition of breast milk is influenced by gestational and postnatal age, as well as by the moment of the feed. Breastfeeding is associated with slightly enhanced performance on tests of cognitive development. Exclusive breastfeeding for at least 3 months is associated with a lower incidence and severity of diarrhoea, otitis media and respiratory infection. Exclusive breastfeeding for at least 4 months is associated with a lower incidence of allergic disease (asthma, atopic dermatitis) during the first 2 to 3 years of life in at-risk infants (infants with at least one first-degree relative presenting with allergy). Breastfeeding is also associated with a lower incidence of obesity during childhood and adolescence, as well as with a lower blood pressure and cholesterolemia in adulthood. However, no beneficial effect of breastfeeding on cardiovascular morbidity and mortality has been shown. Maternal infection with hepatitis B and C virus is not a contraindication to breastfeeding, as opposed to HIV infection and galactosemia. A supplementation with vitamin D and K is necessary in the breastfed infant. Very few medications contraindicate breastfeeding. Premature babies can be breastfed and/or receive mother's milk and/or bank milk, provided they receive energy, protein and mineral supplements. Return to prepregnancy weight is earlier in breastfeeding mothers during the 6 months following delivery. Breastfeeding is also associated with a decreased risk of breast and ovarian cancer in the premenopausal period, and of osteoporosis in the postmenopausal period.
    Archives de pediatrie : organe officiel de la Societe francaise de pediatrie. 11/2013; 20S2:S29-S48.
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    ABSTRACT: Preeclampsia is a pregnancy disorder characterized by hypertension and proteinuria. In preeclampsia, the placenta releases factors into the maternal circulation that cause a systemic endothelial dysfunction. Herein, we investigated the effects of plasma from women with preeclamptic and normal pregnancies on the transcriptome of an immortalized human umbilical vein endothelial cell line. The cells were exposed for 24 hours to preeclamptic or normal pregnancy plasma and their transcriptome was analyzed using Agilent microarrays. A total of 116 genes were found differentially expressed: 71 were up-regulated and 45 were down-regulated. In silico analysis revealed significant consistency and identified four functional categories of genes: mitosis and cell cycle progression, anti-apoptotic, fatty acid biosynthesis, and endoplasmic reticulum stress effectors. Moreover, several genes involved in vasoregulation and endothelial homeostasis showed modified expression, including EDN1, APLN, NOX4, and CBS. Promoter analysis detected, among the up-regulated genes, a significant overrepresentation of genes containing activation protein-1 regulatory sites. This correlated with down-regulation of JDP2, a gene encoding a repressor of activation protein-1. The role of JDP2 in the regulation of a subset of genes in the human umbilical vein endothelial cells was confirmed by siRNA inhibition. We characterized transcriptional changes induced by preeclamptic plasma on human umbilical vein endothelial cells, and identified, for the first time to our knowledge, JDP2 as a regulator of a subset of genes modified by preeclamptic plasma.
    American Journal Of Pathology 10/2013; · 4.60 Impact Factor
  • European Society For Magnetic Resonance in Medicine and Biology, Toulouse - France; 10/2013
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    ABSTRACT: Protein energy malnutrition (PEM) occurs when energy and protein intake do not meet requirements. PEM increases both morbidity and mortality of a given disease. The Nutrition Committee of the French Paediatric Society recommends weighing and measuring any child when hospitalized or seen as outpatients. Body mass index (BMI) must be calculated and analyzed according to references anytime growth kinetics cannot be analyzed. Any child with a BMI below the third centile or –2 standard deviations for age and sex needs to be examined looking for clinical signs of malnutrition and signs orienting toward an aetiology, and requires having his BMI and height dynamics plotted on a chart. PEM warrants drawing a nutritional strategy along with the global care plan. A target weight needs to be determined as well as the quantitative, qualitative and modality of nutritional care. This plan must be evaluated afterwards in order to adapt nutritional therapy.
    Nutrition Clinique et Métabolisme 09/2013; 27(3):156–159. · 0.33 Impact Factor
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    ABSTRACT: Abstract Objective. Low birth weight (LBW) is a risk factor for hypertension at adulthood. Endothelial progenitor cells (EPCs) dysfunction has been characterized in LBW neonates. We hypothesized that changes in soluble, plasma pro- or anti-angiogenic factors are associated with EPCs dysfunction and impaired angiogenesis in LBW neonates. Methods. Venous umbilical cord blood was collected from 42 normal, term neonates and 75 LBW neonates. Cord blood endothelial colony forming cells (ECFC) from control patients were cultured in the presence of 10 % of serum obtained from both groups. Results. The proliferation and the migration of ECFC were significantly reduced when cultured with 10 % of serum of LBW neonates compared to serum of control neonates. Matrigel invasion assay was not significantly altered. Umbilical vein plasma VEGF concentration was significantly reduced in LBW neonates while that of sVEGFR and PF4 were significantly higher. Addition of VEGF corrected the inhibitory effect of LBW serum on normal ECFC proliferation. Conclusions. Serum obtained from low birth weight babies contains factors that exhibit an antiangiogenic effect on ECFC proliferation and migration. VEGF/sVEGF/PF4 pathway seems to be involved in the EPCs dysfunction in LBW neonates.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 05/2013; · 1.36 Impact Factor
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    ABSTRACT: Processed baby foods designed for infants (4–12 months) and toddlers (12–36 months) (excluding infant formula, follow-on formula, the so-called growing-up milks, and cereal-based foods for infants), which are referred to as baby foods, are specific products defined by a European regulation (Directive 2006/125/CE). According to this Directive, such foods have a composition adapted to the nutritional needs of children of this age and should comply with specifications related to food safety in terms of ingredients, production processes, and prevention of infectious and toxicological hazards. Hence, they differ from ordinary foods and from non-specific processed foods. This market segment includes the full range of foods that can be part of children's diet: dairy products (dairy desserts, yoghurts, and fresh cheese), sweet products (nondairy desserts, fruit, and drinks), and salty products (soups, vegetable-based foods, meat, fish, and full dishes). This market amounted to 89,666 MT in France in 2011 and 83,055 MT in 2010 (a total of 325,524 MT in the 27 countries of the European Union in 2010, including 90,438 MT in Germany, 49,144 MT in Spain, and 40,438 MT in Italy). The consumption of baby foods in France varies with infant age and parental choice. Baby foods account for 7 % of total energy intake at 4–5 months, 28 % at 6–7 months, 27 % at 8–11 months, 17 % at 1–17 months, and 11 % at 18–24 months. Among parents, 24 % never offer their children any baby foods, 13 % do so 1–3 days/week and 63 % 4–7 days/week. Among consumers, 55 % of children eat more than 250 g/day of baby foods. As baby foods only account for a minor fraction of overall food intake, their impact on the quality of young children's diet is much less than that of growing-up milks, particularly for preventing insufficient iron and vitamin D intake. Their consumption, however, has an indirect benefit on the nutritional quality of the diet and on food safety, particularly regarding toxicological hazards, as it postpones the introduction of non-specific processed foods, which are inadequate for this age group owing to both their nutritional composition and lower food safety control. Baby foods represent a family of products meeting parents’ expectations and adapted to infants and young children. They are clearly beneficial in terms of food safety, but the nutritional benefit to be expected from their consumption is minimal: their main advantage is postponing or decreasing the consumption of non-specific industrially processed foods.
    Archives de Pédiatrie. 05/2013; 20(5):523–532.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Processed baby foods designed for infants (4-12months) and toddlers (12-36months) (excluding infant formula, follow-on formula, the so-called growing-up milks, and cereal-based foods for infants), which are referred to as baby foods, are specific products defined by a European regulation (Directive 2006/125/CE). According to this Directive, such foods have a composition adapted to the nutritional needs of children of this age and should comply with specifications related to food safety in terms of ingredients, production processes, and prevention of infectious and toxicological hazards. Hence, they differ from ordinary foods and from non-specific processed foods. This market segment includes the full range of foods that can be part of children's diet: dairy products (dairy desserts, yoghurts, and fresh cheese), sweet products (nondairy desserts, fruit, and drinks), and salty products (soups, vegetable-based foods, meat, fish, and full dishes). This market amounted to 89,666 MT in France in 2011 and 83,055 MT in 2010 (a total of 325,524 MT in the 27 countries of the European Union in 2010, including 90,438 MT in Germany, 49,144 MT in Spain, and 40,438 MT in Italy). The consumption of baby foods in France varies with infant age and parental choice. Baby foods account for 7 % of total energy intake at 4-5months, 28 % at 6-7months, 27 % at 8-11months, 17 % at 1-17months, and 11 % at 18-24months. Among parents, 24 % never offer their children any baby foods, 13 % do so 1-3 days/week and 63 % 4-7days/week. Among consumers, 55 % of children eat more than 250g/day of baby foods. As baby foods only account for a minor fraction of overall food intake, their impact on the quality of young children's diet is much less than that of growing-up milks, particularly for preventing insufficient iron and vitamin D intake. Their consumption, however, has an indirect benefit on the nutritional quality of the diet and on food safety, particularly regarding toxicological hazards, as it postpones the introduction of non-specific processed foods, which are inadequate for this age group owing to both their nutritional composition and lower food safety control. Baby foods represent a family of products meeting parents' expectations and adapted to infants and young children. They are clearly beneficial in terms of food safety, but the nutritional benefit to be expected from their consumption is minimal: their main advantage is postponing or decreasing the consumption of non-specific industrially processed foods.
    Archives de Pédiatrie 04/2013; · 0.36 Impact Factor
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    ABSTRACT: Preeclampsia (PE) is a common human-specific pregnancy disorder defined by hypertension and proteinuria during gestation and responsible for maternal and fetal morbimortality. STOX1, encoding a transcription factor, was the first gene associated with PE as identified by positional cloning approaches. Its overexpression in choriocarcinoma cells mimics the transcriptional consequences of PE in the human placenta. Here, we created transgenic mouse strains overexpressing human STOX1. Wild-type female mice crossed with transgenic male mice reproduce accurately the symptoms of severe PE: gestational hypertension, proteinuria, and elevated plasma levels of soluble fms-like tyrosine kinase 1 and soluble endoglin. Placental and kidney histology were altered. Symptoms were prevented or alleviated by aspirin treatment. STOX1-overexpressing mice constitute a unique model for studying PE, allow testing therapeutic approaches, and assessing the long-term effects of the preeclamptic syndrome.
    Hypertension 01/2013; · 6.87 Impact Factor

Publication Stats

1k Citations
422.46 Total Impact Points

Institutions

  • 2014
    • University Hospital of Lausanne
      Lausanne, Vaud, Switzerland
  • 2005–2014
    • Aix-Marseille Université
      • • Faculté de Pharmacie
      • • Faculté de Médecine
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2013
    • Institut Cochin
      Lutetia Parisorum, Île-de-France, France
    • Paul Sabatier University - Toulouse III
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 2001–2013
    • Assistance Publique Hôpitaux de Marseille
      • Service de médecine interne
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2012
    • Université René Descartes - Paris 5
      Lutetia Parisorum, Île-de-France, France
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 2010
    • Centre Hospitalier Universitaire de Rennes
      Roazhon, Brittany, France
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 2008
    • Ospedale Maggiore Carlo Alberto Pizzardi di Bologna
      Bolonia, Emilia-Romagna, Italy
  • 2007
    • Centre National de Génotypage
      Évry-Petit-Bourg, Île-de-France, France
  • 2002
    • Hôpital Universitaire Necker
      Lutetia Parisorum, Île-de-France, France
  • 1988–1999
    • University of Strasbourg
      • • Institut de Bactériologie
      • • Faculty of Medicine
      Strasburg, Alsace, France
  • 1992
    • CHRU de Strasbourg
      Strasburg, Alsace, France