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International audience; Background: Aggressiveness is a stigma frequently associated with schizophrenia. The role of insight as a risk factor of aggressiveness remains contradictory; mainly because single measures of these states mask their complexity and heterogeneity.Methods: This study was conducted on 666 patients aged 15 and above with a DSM-IV-TR diagnosis of schizophrenia spectrum disorder, drawn from the French national network of schizophrenia expert center database. Collected data comprised socio-demographics and standardized psychiatric assessments. Aggressiveness was evaluated using the Buss-Perry Aggression Questionnaire and insight using the Scale to assess Unawareness of Mental Disorder (SUMD) and Birchwood Insight Scale (BIS).Results: Hostility was the aggressiveness dimension the most strongly associated with SUMD insight dimensions. Patients aware of their illness were nearly twice as likely to show hostility than those seriously unaware (OR = 1.95, 95% CI.: 1.08-3.5), but not when further adjusting for depression. Similarly, those aware of the consequences of their illness and of their symptoms were more hostile. Patients moderately aware of illness consequences had a higher risk of both anger and physical aggressiveness than those unaware (OR = 2.63, 95% CI.: 1.42-4.86, OR = 2.47, 95% CI.: 1.33-4.60, respectively), even when adjusting for depression for anger.Conclusion: Our study confirms that a multi-dimensional approach to insight and aggressiveness is essential to understand the types of links between these clinical states. Insight may trigger the expression of an underlying hostile tendency, maybe via depression and self-stigmatisation. This should be taken into account in therapeutic approaches to improve insight.

Background Coronavirus disease COVID-19 has become a public health emergency of international concern. Together with the quest for an effective treatment, the question of the post-infectious evolution of affected patients in healing process remains uncertain. Krebs von den Lungen 6 (KL-6) is a high molecular weight mucin-like glycoprotein produced by type II pneumocytes and bronchial epithelial cells. Its production is raised during epithelial lesions and cellular regeneration. In COVID-19 infection, KL-6 serum levels could therefore be of interest for diagnosis, prognosis and therapeutic response evaluation. Materials and methods Our study retrospectively compared KL-6 levels between a cohort of 83 COVID-19 infected patients and two other groups: healthy subjects (n = 70) on one hand, and a heterogenous group of patients suffering from interstitial lung diseases (n = 31; composed of 16 IPF, 4 sarcoidosis, 11 others) on the other hand. Demographical, clinical and laboratory indexes were collected. Our study aims to compare KL-6 levels between a COVID-19 population and healthy subjects or patients suffering from interstitial lung diseases (ILDs). Ultimately, we ought to determine whether KL-6 could be a marker of disease severity and bad prognosis. Results Our results showed that serum KL-6 levels in COVID-19 patients were increased compared to healthy subjects, but to a lesser extent than in patients suffering from ILD. Increased levels of KL-6 in COVID-19 patients were associated with a more severe lung disease. Discussion and conclusion Our results suggest that KL-6 could be a good biomarker to assess ILD severity in COVID-19 infection. Concerning the therapeutic response prediction, more studies are necessary.

Small cell lung cancer is a malignant tumour with a poor prognosis. Standard treatment of metastatic stages has been a platinum doublet since 1980, but the addition of immunotherapy has improved prognosis. For locally advanced stages, the combination of radio-chemotherapy remains the treatment of choice, with no evidence at present of the value of immunotherapy in consolidation, and for localized stages, surgery is the first-line therapy. Unfortunately, in the second line, we have no other molecule than the topotecan despite several studies. Prophylactic brain irradiation remains debated even if it has been validated in localized forms. Finally, there is hope with targeted therapy following the development of subtypes of small cell lung cancer but studies remain difficult to conduct.Le cancer pulmonaire à petites cellules est une tumeur maligne de mauvais pronostic. Le traitement standard des stades métastatiques était un doublet à base de sels de platine depuis 1980, mais l’ajout de l’immunothérapie a, quand même, permis d’améliorer le pronostic. Pour les stades localement avancés, l’association d’une radiochimiothérapie reste le traitement de choix, sans évidence actuellement de l’intérêt d’une immunothérapie en consolidation, et pour les stades localisés, la chirurgie. Malheureusement, en deuxième ligne, nous n’avons pas d’autre molécule que le topotécan malgré plusieurs études. L’irradiation cérébrale prophylactique reste débattue, même si elle a été validée dans les formes localisées. Enfin, il existe un espoir avec une thérapie ciblée suite à la mise en évidence de sous-types de cancers pulmonaires à petites cellules, mais les études restent difficiles à mener.

Lung cancer is the third most common cancer in Belgium in 2017 and remains the leading cause of cancer death worldwide. There is no longer any doubt that the main cause of lung cancer is smoking. However, the prevalence of lung cancer in never-smokers has been increasing overtime. Moreover, it is now recognized that the lung cancer of non-smoker patients has very distinct characteristics. In this retrospective cohort study (N = 520), we describe the characteristics of non-smoker patients and their non-small cell lung carcinoma and compare them to those of smokers. The patients included in this study were whose with a new diagnostic of lung cancer made at the Liège University Hospital of Liège over 2 years round. Non small cell lung cancer occurring in never-smokers patients is more often seen in young and very old patients, more frequent in female, essentially adenocarcinoma and often associated with mutations. This work confirms that lung cancer in never-smokers shows different features than lung cancer seen in patients with a smoking history.Le cancer pulmonaire est le troisième cancer le plus fréquent en Belgique en 2017 et reste la première cause de décès par cancer dans le monde. Il ne fait plus aucun doute que la cause principale de cancer du poumon est le tabagisme. Il est toutefois apparu, ces dernières décennies, que le pourcentage de patients non fumeurs augmente parmi les patients présentant un cancer du poumon. Par ailleurs, il est dorénavant reconnu que le cancer pulmonaire du patient non fumeur présente des caractéristiques bien distinctes. Dans ce contexte, nous présentons une étude rétrospective reprenant les caractéristiques cliniques et néoplasiques de l’ensemble des patients ayant présenté un carcinome pulmonaire non à petites cellules dans notre institution sur une période de 2 ans (N = 520). Les cancers non à petites cellules observés chez les nonfumeurs sont plus fréquents chez les sujets jeunes ou très âgés, plus fréquents dans le sexe féminin, en très grande majorité des adénocarcinomes, et souvent associés à des mutations. Nous confirmons ainsi qu’il s’agit d’un cancer aux caractéristiques différentes des cancers pulmonaires des patients fumeurs.

The majority of non-small cell lung cancers are diagnosed as advanced disease. Subsets of adenocarcinomas and of squamous cell carcinomas in nonsmokers present a molecular aberration leading to tumour survival. Epidermal Growth Factor Receptor (EGFR), Anaplastic Lymphoma Kinase (ALK) and Repressor Of Silencing1 (ROS1) have been identified and targeted with good efficacy for fifteen years. Newer inhibitors brought even greater efficacy with a generally better tolerability. Other molecular aberrations (Kirsten Rat Sarcoma, Rearranged during Transfection, MET, NeuroTrophic Receptor yrosine kinase) are targets for newly developed, more selective drugs. As more and more patients will benefit from targeted therapies, the identification of molecular aberration is more than ever crucial for optimal lung cancer patient care.La majorité des cancers pulmonaires non à petites cellules se présentent à un stade avancé. Une faible proportion des adénocarcinomes et des cancers épidermoïdes des non-fumeurs est porteur d’(une) anomalie(s) génétique (s) et moléculaire(s) dont dépend leur survie. Depuis une quinzaine d’années, les anomalies de l’«Epidermal Growth Factor Receptor» (EGFR), «Anaplastic Lymphoma Kinase» (ALK) et Repressor Of Silencing1 (ROS1) sont connues et ciblées par des inhibiteurs efficaces. De nouvelles générations permettent actuellement d’augmenter leur efficacité thérapeutique pour une toxicité globalement moindre. De nouvelles anomalies («Kirsten Rat Sarcoma», «Rearranged during Transfection», MET, «NeuroTrophic Receptor tyrosine kinase») sont, elles aussi, à présent ciblées de manière efficace. La recherche des anomalies moléculaires dans ces sous-types histologiques est devenue incontournable car elle modifie fondamentalement la prise en charge thérapeutique et le pronostic d’une proportion grandissante de patients.

Neuroendocrine neoplasms are histologically defined by a common neuroendocrine cellular phenotype. These are still considered as rare tumours even though their incidence is increasing. Heterogeneity is everywhere whether in the localization of the primitive cancer, the clinical presentation, the histological classification, the prognosis, as well as in therapeutic options, which clearly justifies specialized multidisciplinary care. Heterogeneity and scarcity explain the still fragmented nature of knowledge in this domain. Thanks to an increase in incidence, a desire for standardization of classification as well as the arrival of major therapeutic advances, such as vectorized internal radiotherapy, the future of neuroendocrine neoplasia seems more than promising and exciting. In our daily clinical practice at CHU Liège, we hope to bring our stone to the building by listing as many cases as possible in national and/or international databases, by centralizing therapeutic discussions within specific multidisciplinary concertations and by participating in multicenter study protocols.Les néoplasies neuroendocrines sont définies histologiquement par un phénotype cellulaire neuroendocrine commun. Ces néoplasies sont toujours considérées comme des tumeurs rares, bien que leur incidence soit en constante augmentation. L’hétérogénéité est omniprésente, que ce soit dans la localisation du cancer primitif, la présentation clinique, la classification histologique, le pronostic ainsi que dans les diverses options thérapeutiques, justifiant impérativement une prise en charge pluridisciplinaire spécialisée. Cette hétérogénéité et cette rareté expliquent que les connaissances soient parcellaires. Grâce à une majoration d’incidence, une volonté d’uniformisation de classification ainsi que l’arrivée d’avancées thérapeutiques majeures, telles que la radiothérapie interne vectorisée, l’avenir des néoplasies neuroendocrines semble plus que prometteur et palpitant. En pratique clinique quotidienne au CHU de Liège, nous espérons apporter notre pierre à l’édifice en recensant un maximum de cas dans des bases de données nationales et/ou internationales, en centralisant les discussions thérapeutiques au sein de concertations multidisciplinaires dédiées et en participant à des protocoles d’études cliniques multicentriques.

The perception of ventilatory effort is common in oncology, especially but not exclusively in the advanced stages of neoplastic disease. Dyspnea is a symptom whose discomfort and anguish it generates in the patient and his/ her entourage require constant management throughout the illness. The first step is to identify and optimize the treatment of comorbidities associated with tumour disease. Relief of respiratory oppression as a symptom requires a multidisciplinary approach. Opiates and benzodiazepines are at the forefront of pharmacological management. The mechanical obstruction that limits ventilatory flow and/or chest ampliation may justify more invasive management, including endoscopic techniques. Oxygen therapy will be considered on a case-by-case basis. Finally, global management includes respiratory revalidation, psychological support and improvement of environmental quality.La perception d’un effort ventilatoire est fréquente en oncologique en particulier, mais non exclusivement, aux stades avancés de la maladie néoplasique. La dyspnée constitue un symptôme dont l’inconfort et l’angoisse qu’elle génère chez le patient et son entourage nécessitent une prise en charge constante tout au long de la maladie. La première étape est d’identifier et d’optimaliser le traitement des pathologies dyspnéisantes conjointes à la maladie tumorale. Le soulagement de l’oppression respiratoire en tant que symptôme nécessite une approche pluridisciplinaire. Les opiacés et les benzodiazépines sont au premier plan de la prise en charge pharmacologique. La levée d’un obstacle mécanique limitant les débits ventilatoires et/ou l’ampliation thoracique peut justifier des techniques plus invasives, notamment endoscopiques. L’oxygénothérapie sera envisagée au cas par cas. Enfin, la prise en charge globale inclut la revalidation respiratoire, le support psychique et l’amélioration de la qualité de l’environnement.

Resume Introduction L’incidence des maladies de la plevre continue a augmenter a travers le monde. La thoracoscopie medicale demeure l’examen de reference dans l’exploration de la cavite pleurale. Methode Nous rapportons l’evaluation retrospective, l’efficacite et les complications observees des 1024 thoracoscopies medicales adressees au CHU de Liege entre 2000 et 2017. Resultats Cent pneumothorax, 400 atteintes pleurales benignes et 501 malignes ont ete colligees. L’indication premiere de la thoracoscopie demeure l’exploration d’une pleuresie exsudative lymphocytaire d’etiologie inconnue apres thoracocentese. Sa sensibilite diagnostique etait de 99,2 % dans l’identification d’une pleuropathie maligne. Une pleurodese au talc a ete realisee dans 69,5 % de la population globale et chez 66,1 % des atteintes pleurales solides ou liquidiennes. Un echec de pleurodese a ete observe dans 11 % des patients presentant un pneumothorax recidivant et chez 7,8 % des pleuresies neoplasiques talquees. Une mortalite de 0,6 % a 30 jours, un drainage prolonge dans 8,3 %, et 4,7 % de complications graves ont ete colliges. Au total, 22/1024 (2,1 %) des thoracoscopies n’ont pu etre realisees en raison d’une fibrose pleurale non dissecable. Conclusion La thoracoscopie medicale est un examen simple et bien tolere. Elle presente une excellente rentabilite dans la prise en charge diagnostique et therapeutique des maladies pleurales.

Treatment-resistant schizophrenia (TRS) affects around 30% of patients with schizophrenia (SZ) resulting in poor functioning, relapses, and reduced quality of life. Convergent findings show that inflammation could contribute to resistance. We thus search for immune signatures of patients with TRS/ultra TRS (UTRS) in a sample of community-dwelling outpatients with SZ. In total, 195 stabilized SZ patients (mean age = 31.2 years, 73% male gender) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia in France and received a thorough clinical assessment. At inclusion, psychotic symptomatology was evaluated by the Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Circulating serum/plasma levels of a large panel of markers reflecting the main inflammatory pathways were evaluated. TRS was defined by current treatment by clozapine (CLZ) and UTRS by current CLZ treatment + PANSS total score ≥ 70. The frequency of TRS and UTRS patients was, respectively, 20% and 7.7% and was defined using multivariable analysis elevated by high levels of interleukin (IL)-12/IL-23p40, IL-17A, IL-10, and beta 2 microglobulin (B2M) and IL-12/IL-23p40, IL-17A, IL-6, IL-10, IFNγ, and B2M, respectively. These observations suggest that resistance and ultra resistance to CLZ treatment are underpinned by pro-inflammatory molecules mainly belonging to the T helper 17 pathway, a finding making sense given the interplay between inflammation and antipsychotic treatment responses. If confirmed, our findings may allow us to consider IL-23/IL-17 pathway as a therapeutic target for patients with resistance to antipsychotics.

Background Asthmatics and COPD patients have more severe outcomes with viral infections than people without obstructive disease. Objective To evaluate if obstructive diseases are risk factors for ICU stay and death due to COVID19. Methods We collected data from the electronic medical record from 596 adult patients hospitalized in University hospital of Liege between 18th of March and 17th of April 2020 for SARS-CoV2 infection. We classified patients in three groups according to the underlying respiratory disease, present prior to COVID19 pandemics. Results Among patients requiring hospitalization for COVID19, asthma and COPD accounted for 9.6% and 7.7% respectively. The proportions of asthmatics, COPD and patients without obstructive airway disease hospitalized in ICU were 17.5%, 19.6% and 14% respectively. One third of COPD patients died during hospitalization while only 7.0% of asthmatics and 13.6% of patients without airway obstruction died due to SARS-CoV2. The multivariate analysis showed that asthma, COPD, ICS treatment and OCS treatment were not independent risk factors for ICU admission or death. Male gender (OR:1.9; 95%CI: 1.1 to 3.2) and obesity (OR:8.5; 95%CI: 5.1 to 14.1) were predictors of ICU admission while male gender (OR1.9; 95%CI: 1.1-3.2), older age (OR:1.9; 95%CI: 1.6-2.3), cardiopathy (OR: 1.8; 95%CI: 1.1-3.1) and immunosuppressive diseases (OR: 3.6; 95%CI: 1.5-8.4) were independent predictors of death. Conclusion Asthma and COPD are not risk factors for ICU admission and death related to SARS-CoV2 infection., Highlights What is already known about this topic? Asthmatics and COPD patients are at risk of more severe outcomes with common cold virus infections. Prior studies have suggested that allergic diseases, asthma and COPD may not be risk factors for SARS-CoV-2 infection. What does this article add to our knowledge? The strength of this study is the characterization of obstructive disease according to lung function testing. In our study, asthma, COPD, treatment with ICS or OCS were not risk factors for admission to the ICU or mortality. How does this study impact current management guidelines? Our results confirm the recommendations that patients with obstructive airway disease should not decrease the dose of ICS during SARS-CoV2 infection. Asthma and COPD treatments should be pursued and adapted to ensure optimal control of the lung disease throughout the pandemic, potentially reducing the risk of severe COVID19 disease.

Introduction Patients with interstitial lung diseases (ILD) can be suspected to be at risk of experiencing a rapid flare-up due to COVID-19. However, no specific data are currently available for these patients. Methods We retrospectively analyzed a cohort of 401 patients with ILD and determined the proportion of patients hospitalized for proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and specific symptoms of COVID-19. Results We found that 1% of patients (n = 4) were hospitalized (1 in ICU) for COVID-19. In total, 310 of the 401 patients answered the phone call. Only 33 patients (0.08%) experienced specific symptoms of SARS-CoV-2 infection. Conclusion Our study did not demonstrate any increased occurrence of severe COVID-19 in ILD patients compared to the global population. Based on our findings, we could not make any conclusion on the incidence rate of SARS-CoV-2 infection in patients with ILDs, or on the overall outcome of immunocompromised patients affected by COVID-19.

Background: No specific safety data concerning systemic oncological treatments were available at time of COVID-19 outbreak in Belgium. In our hospital we decided to maintain adjuvant and early line treatments for metastatic disease in patients under 65 and without specific comorbidities and to apply a shared decision approach in other patients while following closely the safety of these treatments. Method(s): Real time safety monitoring was proposed to all patients treated for solid tumours in our day-care unit starting March 1st, 2020. After signing informed consent patients were asked questions concerning protective measures at home, signs of SARS-CoV-2 infection and hospitalisation. Patients' charts were reviewed for outcome, including death, after suspected or proven SARS-CoV-2 infection. Minimum follow-up was 5 weeks after day care unit attendance. Result(s): 387 patients were included in our registry between March 1st and March 31st, 2020. Median age was 64 years-old (range 27-90). Most patients suffered from lung (n=96), breast (n=93), gastrointestinal (n=87), gynaecological (n=38) or urological (n=33) cancers. 131 patients received (neo)adjuvant treatments, 256 patients were treated for metastatic disease. Patients received chemotherapy (n=170), immunotherapy (n=103), targeted therapy (n=68) or other combinations (n=46). Although Belgium had one of the highest infection rates in the world, safety data concerning risk of SARS-CoV-2 infection and outcomes were rather reassuring. A total of 11 patients had either suspected (n=5, 1.3%) or proven (n=6, 1.6%) SARS-CoV-2 infection. Only one 74 years old patient died of COVID-19, another 51 years old patient died of progressive disease but presented also suspicion of SARS-CoV-2 infection at the time of death. Conclusion(s): Analysis of our data for patients treated in March 2020 in the day-care unit are reassuring and suggest higher risk related to under-treatment compared to risk related to continuation of systemic therapy at time of COVID-19 outbreak. Patients' follow-up will be updated and additional analyses and data in particular for April 2020, when the infection rate was still extremely high in Belgium, will be presented. Legal entity responsible for the study: The authors. Funding(s): Fondation Leon Fredericq. Disclosure: A. Rorive: Travel/Accommodation/Expenses: BMS;MSD. B. Sautois: Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen;Advisory/Consultancy: Clovis;Sanofi;Astellas. J. Collignon: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche;Amgen;Pfizer;Advisory/Consultancy: Servier;Bayer;Merck;Lilly;Sanofi;Sirtex;Celgene;Ipsen;Novartis. P. Freres: Advisory/Consultancy: Ipsen;Merck;BMS. C. Gennigens: Advisory/Consultancy, Research grant/Funding (institution): Astra-Zeneca;Advisory/Consultancy: BMS;GSK;Lilly;MSD;Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen;Pfizer;Pharmamar;Roche. G. Jerusalem: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis;Roche;Pfizer;Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Lilly;Advisory/Consultancy, Research grant/Funding (institution): Amgen;Advisory/Consultancy, Travel/Accommodation/Expenses: BMS;AstraZeneca;Daiichi Sankyo;Advisory/Consultancy: Abbvie;Travel/Accommodation/Expenses: Medimmune;MerckKGaA. All other authors have declared no conflicts of interest.Copyright © 2020

© 2020, The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare. Smac mimetics target inhibitor of apoptosis (IAP) proteins, thereby suppressing their function to facilitate tumor cell death. Here we have evaluated the efficacy of the preclinical Smac-mimetic compound A and the clinical lead birinapant on breast cancer cells. Both exhibited potent in vitro activity in triple-negative breast cancer (TNBC) cells, including those from patient-derived xenograft (PDX) models. Birinapant was further studied using in vivo PDX models of TNBC and estrogen receptor-positive (ER+) breast cancer. Birinapant exhibited single agent activity in all TNBC PDX models and augmented response to docetaxel, the latter through induction of TNF. Transcriptomic analysis of TCGA datasets revealed that genes encoding mediators of Smac-mimetic-induced cell death were expressed at higher levels in TNBC compared with ER+ breast cancer, resulting in a molecular signature associated with responsiveness to Smac mimetics. In addition, the cell death complex was preferentially formed in TNBCs versus ER+ cells in response to Smac mimetics. Taken together, our findings provide a rationale for prospectively selecting patients whose breast tumors contain a competent death receptor signaling pathway for the further evaluation of birinapant in the clinic.

Introduction et but de l’etude Les donnees epidemiologiques de la Nutrition Enterale a Domicile (NED) et de la Nutrition Parenterale a Domicile (NPD) pediatriques ont pu etre partiellement determinees a partir de donnees regionales respectivement en 2011 [1] , et en 2016 [2] . Toutefois, il n’y a pas de donnees epidemiologiques effectuees sur l’ensemble du territoire, et notamment de donnees de NED et NPD disponibles simultanement la meme annee. Materiel et methodes Selon la Methode utilisee pour les etudes epidemiologiques anterieures [1] , [2] , et a l’aide des codes de la liste des produits et prestations (LPP) et des donnees des Affections de longue duree (ALD), il a ete demande a la Caisse Nationale d’Assurance Maladie (CNAM) de communiquer les donnees 2017 concernant les enfants ( – la nombre de nouveaux patients pris en charge en NED et NPD (ce qui rapporte a la population cible permet le calcul de l’incidence), – Le nombre total de patients pris en charge en NED et NPD (pour le calcul de la prevalence), – de croiser ces resultats avec les fichiers ALD. Les enfants ont ete regroupes en 2 tranches d’âge (0 a 4 ans et 5 a 14 ans) et en 7 categories de pathologies : cancerologie, neurologie, maladies intestinales chroniques inflammatoires (MICI), insuffisances d’organes, maladies metaboliques, autres ALD et ALD hors liste. Resultats et analyse statistique Les donnees obtenues concernent la population du regime general de la securite sociale et les sections locales mutualistes soit 61 880 672 personnes representant 92,1 % de la totalite de la population francaise. Incidence (Inc) et prevalence (Prev) de la NED et NPD pediatriques ( Inc NED Prev NED Inc NPD Prev NPD globale Prev NPD > 12sem 0 a 4 ans 27,7 69,7 1,4 3,7 2,8 5 a 14 ans 6,9 43,6 0,4 2,0 1,7 Total 13,5 51,9 0,7 2,6 2,1 Au total, en 2017, 5755 enfants ont ete pris en charge en NED et 285 enfants en NPD (dont 230 pour une NPD > 12 semaines). Pour les 7 categories de pathologies (cancerologie, neurologie, MICI, insuffisance d’organe, maladies metaboliques, autres ALD et ALD hors liste), la repartition etait successivement pour la NED de 7,1 %, 31,7 %, 4,3 %, 16 %, 12,4 %, 2,5 %, et 31,2 %. A noter que plusieurs ALD sont possibles chez un meme patient. Pour la NPD, seules les ALD hors listes ont ete comptabilisees representant 80 % des pathologies. Les chiffres precis des autres pathologies n’ont pas ete donnes par la CNAM pour des raisons de confidentialite (faibles nombres). Conclusion Il s’agit de la premiere etude epidemiologique nationale concernant la meme annee la NED et la NPD chez l’enfant. Ces donnees confirment l’importance du polyhandicap en NED (majoritaire dans les affections neurologiques et hors liste = 62, % de la NED). Pour la NPD, les ALD hors listes sont les plus frequentes : en effet les indications de NPD sont dominees par le syndrome de grele court congenital ou neonatal precoce (atresie du grele, enterocolite ulceronecrosante) et les dysmotricites digestives (Hirchprung et pseudo obstrucion intestinale chronique).

International audience; Objectives The present article is a synthesis of the first 10 years of follow-up of the FondaMental Academic Center of Expertise for Schizophrenia (FACE-SZ) cohort. Methods More than 700 community-dwelling stabilized subjects have been recruited and evaluated to date. The mean age was 32 years with 75 % males, the mean illness duration was 11 years, the mean age at illness onset was 21 years, the mean duration of untreated psychosis was 1.5 years and 55 % were current daily tobacco smokers. Results The major findings of the FACE-SZ cohort may be summarized as follows: the metabolic syndrome is twice more frequent in schizophrenia as compared to the general population and is not correctly assessed and treated; cognitive disturbances have been found in benzodiazepine consumers and in patients with chronic low-grade peripheral inflammation; major depressive disorder (MDD) is a common current comorbid condition in about 20% of the subjects at the evaluation. MDD is associated with impaired quality of life and with increased nicotine dependency in SZ daily tobacco smokers. Improving depression and negative symptoms may be the most effective strategies to improve quality of life in schizophrenia; the duration of untreated psychosis is much longer in cannabis smokers and in subjects with an age at illness onset < 19 years. Adherence to treatment is diminished in subjects who report a subjective negative feeling after treatment intake independent of objective side effects (extrapyramidal syndrome and weight gain). Akathisia has been found in 18% of the subjects and has been associated with antipsychotic polytherapy. Conclusions In the light of these results, some recommendations for clinical care may be suggested. The early detection of schizophrenia should be specifically increased in adolescents and/or cannabis smokers. All patients should be administered a comprehensive neuropsychological evaluation at the beginning of the illness and after stabilization under treatment. Improving metabolic parameters and lifestyle (diet and physical activity) should be reinforced. The benefit/risk ratio of benzodiazepine and antipsychotic polytherapy should be regularly reevaluated and withdrawn as soon as possible. If MDD remains underdiagnosed and undertreated, improving depression may strongly improve the quality of life of SZ subjects. In the end, Cognitive Remediation Therapy and anti-inflammatory strategies should be more frequently included in therapeutic strategies.; Objectifs Le présent article propose de faire un retour sur les 10 ans d’expérience du réseau national des 10 centres experts schizophrénie Français, à travers une revue des principales publications scientifiques qui en sont issues. Méthodes À ce jour, les données de plus de 700 patients ont pu être analysées. Globalement, cette population est composée de trois quarts d’hommes, est âgée en moyenne de 32 ans, la durée moyenne de maladie est d’environ 11 ans, l’âge moyen de début de maladie est de 21 ans, la durée de psychose non traitée est d’environ un an et demi. 55 % des sujets sont consommateurs de tabac au moment de l’évaluation. Enfin, un focus sera fait sur les projets de recherche multicentriques collaboratifs déployés au sein de ce réseau. Résultats Les principales données obtenues peuvent être résumées comme suit : le syndrome métabolique reste deux fois plus fréquent dans la schizophrénie qu’en population générale et n’est pas correctement pris en charge ; des troubles cognitifs spécifiques ont été identifiés chez les patients consommateurs de benzodiazépines et chez les patients présentant une inflammation périphérique. Des spécificités liées au sexe ont également été observées ; la dépression comorbide reste très fréquente, elle est associée à une diminution de la qualité de vie et à une augmentation de la dépendance nicotinique chez les fumeurs. Prendre en charge la dépression et les symptômes négatifs pourraient fortement améliorer la qualité de vie des patients ; le délai à l’instauration du traitement est plus long pour les schizophrénies se déclenchant avant 19 ans et chez les consommateurs de cannabis. L’adhésion au traitement est diminuée chez les patients rapportant un ressenti subjectif négatif du traitement, indépendamment de la prise de poids ou d’un syndrome extrapyramidal. Enfin, l’akathisie est très fréquente et fortement associée à la polythérapie antipsychotique. Conclusions Ces résultats conduisent à formuler plusieurs recommandations. Le dépistage du trouble et le traitement devraient être renforcés chez les adolescents et les consommateurs de cannabis. Tous les patients devraient bénéficier d’une évaluation neuropsychologique au début de leur trouble, après stabilisation sous traitement, puis de façon plus espacée au cours de leur suivi. La prise en charge des paramètres métaboliques, de l’alimentation et de l’activité physique devrait être renforcée. La balance bénéfice/risque de la prescription de benzodiazépines doit être réévaluée régulièrement au regard de son impact notamment sur la cognition. La monothérapie antipsychotique est recommandée autant que possible pour limiter les effets indésirables. La dépression reste sous-diagnostiquée et doit faire l’objet d’une évaluation systématique et d’un traitement spécifique. La remédiation cognitive doit également être plus largement proposée chez les patients présentant des troubles cognitifs.

Introduction This study aimed was to investigate the relationship between different types of childhood trauma and the level of insight (i.e., awareness of having a psychiatric disorder) in subjects suffering from schizophrenia, as well as the putative role of clinical mediators. Methods 294 community-dwelling subjects with stable schizophrenia were included into FACE-SZ, a multicentre cross-sectional study. All patients were assessed by specialized multidisciplinary teams. The level of insight was assessed by the Scale to assess Unawareness of Mental Disorder (SUMD), and childhood trauma by the Childhood Trauma Questionnaire (CTQ). Path analyses from the five CTQ subscales (physical abuse and neglect, emotional abuse and neglect, and sexual abuse) and the SUMD, with current symptomatology (i.e., positive, negative, global psychopathology and depression) as mediator, was performed. Results Physical neglect (β = 0.14) and abuse (β = 0.13) were significantly associated with poor insight. Negative symptoms were a clinical mediator of the relationship between physical neglect and poor insight. Moreover, positive (β = 0.21) and negative (β = 0.30) symptoms were associated with poor insight, whereas depression (β = −0.14) was associated with higher levels of insight. Discussion For the first time, this study shows a significant relationship between childhood trauma, specifically physical neglect and abuse, and poor insight. The level of insight was linked to different clinical dimensions. Among subjects with schizophrenia, these results provide support for a role of childhood trauma in poorer management outcomes, and the need to provide treatment, including psycho-education that better targets the consequences of childhood trauma.

Background: BRCA1 mutation carriers commonly undergo prophylactic mastectomy to reduce their risk of breast cancer. The precise role of chemoprevention with tamoxifen, which reduces the incidence of ER-positive breast cancer in the general population, is uncertain for BRCA1 mutation carriers, where uptake has been modest. The identification of an effective and acceptable prevention therapy therefore remains a 'holy grail' for the field. Precancerous BRCA1mut/+ tissue harbors an aberrant population of luminal progenitor cells and deregulated progesterone signaling has been implicated in BRCA1-associated oncogenesis. Since Receptor Activator of Nuclear Factor-kappa B ligand (RANKL) is a key paracrine effector of progesterone signaling, and RANKL and its receptor RANK contribute to mammary tumorigenesis, we investigated a role for this pathway in the preneoplastic phase of BRCA1 mutation carriers. Methods: We explored a role for the RANK/RANKL pathway during the preneoplastic phase in freshly isolated (histologically normal) patient specimens from BRCA1 mutation carriers using several approaches. RANK and RANKL expression in breast cancer was evaluated in formalin fixed paraffin embedded (FFPE) archival sections by IHC from the kConFab and the Amgen Tissue Banks. All samples were obtained with patient consent and relevant IRB approval. A role for RANKL inhibition in attenuating tumor onset was studied using the MMTV-cre/Brca1fl/fl/p53+/– mouse model that recapitulates human basal-like breast cancer. Results: We identified two subsets of luminal progenitors (RANK+ and RANK–) in histologically normal tissue of BRCA1 mutation carriers and found that RANK+ cells are highly proliferative, exhibit grossly aberrant DNA repair and bear a molecular signature similar to that of basal-like breast cancer. Moreover, high levels of RANK expression prevailed in established BRCA1-associated tumors. These data suggest that RANK+ and not RANK– progenitors are a key target population in these women. Notably, inhibition of RANKL signaling by denosumab in 3D breast organoids derived from pre-neoplastic BRCA1mut/+ tissue attenuated progesterone-induced proliferation. Furthermore, inhibition of RANKL with either the RANKL inhibitor OPG-Fc or a RANKL monoclonal antibody in a Brca1-deficient mouse model significantly curtailed mammary tumorigenesis, when compared to controls (p Conclusions: Together these findings identify a targetable pathway in a putative cell of origin population in BRCA1 mutation carriers and implicate RANKL blockade as a promising breast cancer prevention strategy. Citation Format: Lindeman GJ, Nolan E, Vaillant F, Branstetter D, Pal B, Giner G, Whitehead L, Lok SW, Mann GB, kConFab Consortium, Rohrbach K, Huang L-Y, Soriano R, Smyth GK, Dougall WC, Visvader JE. RANK ligand as a target for breast cancer prevention in BRCA1 mutation carriers [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr S2-04.

The incidence of pleural disease continues to increase worldwide. Medical thoracoscopy remains the standard method for exploration of the pleural cavity.We report the retrospective evaluation, the efficacy and the observed complications in 1024 medical thoracoscopies undertaken in the University Hospital of Liège between 2000 and 2017.In total, 100 pneumothoraces and 400 benign and 501 malignant pleural diseases were identified. The main indication for thoracoscopy remains the diagnosis of an exudative, lymphocytic pleural effusion of unknown aetiology after thoracocentesis. The diagnostic sensibility of thoracoscopy was 99.2% in distinguishing benign from malignant pleural disease. Talc pleurodesis was performed in 69.5% of the total population and in 66.1% of pleural effusions or thickening. Failure of pleurodesis was observed in 11% of the patients with recurrent pneumothorax and in 7.8% of neoplastic pleural effusion. We report a mortality of 0.6% in the 30 days post procedure, long duration of drainage in 8.3% and serious complications in 4.7%. In 22/1024 (2.1%) thoracoscopic evaluation was not feasible because of dense pleural fibrosis.Medical thoracoscopy is a safe, well-tolerated procedure with high accuracy in the diagnostic and therapeutic management of pleural disease.

Objectives Reducing the duration of untreated psychosis (DUP) may improve the prognosis of schizophrenia. This study investigated the prevalence, and associated risk factors, of long DUP in a large, non-selected sample of community-dwelling schizophrenia patients (SZ). Method 478 community-dwelling stable SZ participants (122 women and 356 men; mean age 32.37 ± 9.86 years) were recruited between 2010 and 2016. The mean retrospective DUP was evaluated from both patient and family reports, as well as hospital/psychiatrists records. Long DUP was defined as > 2 years. Results The mean DUP was 1.5 years. 80 participants (16.7%) had a DUP > 2 years. In multivariate analyses, after adjustment for sex, education level, history of childhood trauma and history of maternal schizophrenia or bipolar disorder, long DUP was associated with a younger age of illness onset (19.3 ± 6.67 years vs. 22.0 ± 6.51 years, adjusted odd ratio aOR = 0.91, 95%CI [0.86; 0.97], p = 0.003) and cannabis use disorder (20.0% vs. 10.3%, aOR = 2.41, 95%CI [1.14–5.09], p = 0.02). Conclusion A high proportion of SZ patients still have a long DUP. The present results suggest that illness onset before age 19 years and cannabis use are associated with long DUP in schizophrenia patients. Early psychosis detection programs should prioritize the targeting of these populations.

International audience; The functional outcome in schizophrenia spectrum disorders is affected by multiple factors such as cognitive performance and clinical symptoms. Psychiatric disability may be another important determinant of functional outcome. The purpose of this study was to test whether schizophrenia symptoms and psychiatric disability mediated the association between cognition and functioning. Between April 2013 and July 2017, we included 108 community-dwelling adults with stable schizophrenia spectrum disorder in a multicenter study. Psychiatric disability was assessed with the Evaluation of Cognitive Processes involved in Disability in Schizophrenia (ECPDS) scale by relatives of patients. ECPDS focused on the broad array of motivational, neurocognitive, sociocognitive, and metacognitive impairments that result in activity restrictions. We used a battery of tests to assess seven cognition domains (processing speed, attention/vigilance, working, verbal and visual memory, reasoning and problem solving, and executive functioning) and cross-sectional structural equation modeling (SEM) for the mediation analyses. We estimated the one-year temporal stability of ECPDS scores in 45 participants. The model provided showed good fit and explained 43.9% of the variance in functioning. The effect of neurocognition on functioning was fully mediated by symptoms (proportion mediated: 36.5%) and psychiatric disability (proportion mediated: 31.3%). The ECPDS score had acceptable one-year temporal stability. The ECPDS scale has satisfactory psychometric properties, and shows significant convergence with neurocognition and functioning, suggesting a role for this tool in the routine evaluation of cognitive remediation needs. Our model validates psychiatric disability as a crucial step from cognitive impairment to restricted participation in life situations.

Supplemental material, Supplemental_Material for Screening for cognitive deficits with the Evaluation of Cognitive Processes involved in Disability in Schizophrenia scale by Paul Roux, Mathieu Urbach, Sandrine Fonteneau, Fabrice Berna, Lore Brunel, Delphine Capdevielle, Isabelle Chereau, Julien Dubreucq, Catherine Faget-Agius, Guillaume Fond, Sylvain Leignier, Claire-Cécile Perier, Raphaëlle Richieri, Priscille Schneider, Franck Schürhoff, Anne Marie Tronche, Hanan Yazbek, Anna Zinetti-Bertschy, the FondaMental Advanced Centers of Expertise in Schizophrenia (FACE-SCZ) Collaborators, Christine Passerieux, Eric Brunet-Gouet, M Andrianarisoa, B Aouizerate, N Bazin, F Berna, O Blanc, L Brunel, E Bulzacka, D Capdevielle, I Chereau-Boudet, G Chesnoy-Servanin, JM Danion, T D’Amato, A Deloge, C Delorme, H Denizot, JM Dorey, C Dubertret, J Dubreucq, C Faget, C Fluttaz, G Fond, S Fonteneau, F Gabayet, E Giraud-Baro, D Lacelle, C Lançon, H Laouamri, M Leboyer, T Le Gloahec, Y Le Strat, PM Llorca, J Mallet, E Metairie, D Misdrahi, I Offerlin-Meyer, C Passerieux, P Peri, S Pires, C Portalier, L Ramet, R Rey, C Roman, A Schandrin, F Schürhoff, A Tessier, AM Tronche, M Urbach, F Vaillant, A Vehier, P Vidailhet, E Vilà, H Yazbek and A Zinetti-Bertschy in Clinical Rehabilitation

Objective Latent Toxoplasma infection has been associated with widespread brain immune activation, increased blood brain barrier permeability, neural disruption, increased dopamine release in dopaminergic neurons, with NMDA activation and with schizophrenia (SZ) onset risk. Toxoplasma has been suggested to be a source of chronic low-grade inflammation and this inflammation has been associated with cognitive impairment in SZ. The objective of the present study were (i) to determine if latent Toxoplasma infection was associated with specific clinical features in stabilized SZ subjects, with cognitive impairment and with increased low-grade peripheral inflammation and (ii) to determine if Treatments with Anti-Toxoplasmic Activity (TATA) were associated with improved outcomes in subjects with latent Toxoplasma infection. Methods A comprehensive 2 daylong clinical and neuropsychological battery was administered in 250 SZ subjects included between 2015 and 2017 in the national FondaMental Expert Center (FACE-SZ) Cohort. Solid phase-enzyme microplate immunoassay methods were used to measure IgG class of antibodies to T. gondii in blood sample. Latent Toxoplasma infection was defined by T . gondii IgG ratio ≥0.8, equivalent to ≥10 international units. Chronic peripheral inflammation was defined by highly sensitive C reactive protein blood level ≥ 3 mg/L. Results Latent Toxoplasma infection has been found in 184 (73.6%) of this national multicentric sample. In the multivariate analyses, latent Toxoplasma infection has been significantly associated with higher PANSS negative (aOR = 1.1 [1.1–1.1], p = 0.04) and excitement subscores (aOR = 1.3 [1.1–1.6], p = 0.01), with two specific symptoms (i.e., reference delusion (aOR = 3.6 [1.2–10.6] p = 0.01) and alogia (aOR = 16.7 [2.0–134.7], p = 0.008)) and with chronic low-grade peripheral inflammation (27.2% vs. 7.6%, aOR = 3.8 [1.4–10.3], p = 0.004). Extrapyramidal symptoms remained significantly associated with latent Toxoplasma infection. On the opposite, no significant association of latent Toxoplasma infection with age, gender, age at SZ onset, suicide behavior or cognitive deficits has been found in these models (all p > 0.05). TATA were associated with lower depressive symptoms (aOR = 0.8[0.7–0.9], p = 0.01), and with lower rates of chronic peripheral inflammation (20.9% vs. 48.6%, aOR = 3.5 [1.5–7.9], p = 0.003) but not with higher cognitive scores (p > 0.05). Conclusion The present findings suggest that Toxoplasma is almost 3 times more frequent in SZ population compared to general population in France. The potential cerebral underpinnings of the association of latent Toxoplasma infection and the above-mentioned outcomes have been discussed. Future studies should confirm that TATA may be effective to reduce Toxoplasma-associated depressive symptoms and low-grade peripheral inflammation.

Discipline Epidemiologie. Introduction et but de l’etude Les donnees epidemiologiques concernant la NPD en France sont meconnues et peu precises. L’arrete de 2014 [1] imposant une prestation pour toute NPD, avec plusieurs forfaits de prise en charge correspondant a des codes de la liste des produits et prestations (LPP), permet actuellement d’obtenir des donnees fiables. Materiel et methodes Selon la methode utilisee pour les donnees epidemiologiques de nutrition enterale a domicile (NED) [2] et a l’aide des codes de LPP et des donnees des affections de longue duree (ALD), il a ete demande aux directions regionales du service medical de l’assurance maladie (DRSM) de l’ensemble du territoire de communiquer : – le nombre de nouveaux patients pris en charge en NPD en 2016 (ce qui a ete rapporte a la population permet le calcul de l’incidence) ; – le nombre total de patients pris en charge en NPD en 2016 (pour le calcul de la prevalence) ; – de croiser ces resultats avec les fichiers d’ALD. Les patients ont ete regroupes en 3 tranches d’âge (15 a 39 ans, 40 a 65 ans et > 65 ans) et en 5 categories (cancerologie, neurologie, maladies intestinales chroniques inflammatoires (MICI), insuffisance d’organe, autres). Resultats et analyse statistique Cinq DRSM ont actuellement repondu (Auvergne–Rhone Alpes, Centre, Hauts de France, Provence-Alpes-Cote d’Azur – Corse, Reunion) correspondant a une population totale de 14 577 618 personnes ( Tableau 1 ). Conclusion Cette etude effectuee sur une population de pres de 15 millions d’habitants de plus de 15 ans retrouve en 2016 une incidence annuelle moyenne de la NPD chez l’adulte de 25,8/100 000 habitants et une prevalence moyenne globale de 33,4/100 000 habitants. La prevalence moyenne de NPD > 12 semaines est de 10,4/100 000 habitants. A partir de ces donnees, une estimation nationale de prevalence en France (59 millions habitants > 15 ans) serait d’environ 19 700 patients adultes/an pris en charge en NPD dont 6100 pendant plus de 12 semaines. La cancerologie est la premiere des indications de NPD (85 %). Les MICI sont la seconde cause de NPD dans la tranche d’âge 15 a 39 ans (28 %). Alors que la NPD doit etre reservee a l’insuffisance intestinale [1] , ces donnees evoquent une vraisemblable utilisation excessive de la NPD au depends de la NED notamment en cancerologie.

Background Tobacco use is common in patients with schizophrenia (SZ) but little is known on the role of tobacco in the physiopathology or on the course of the disease. Only few studies embrace an extensive examination of clinical and therapeutic characteristics in stabilized patients. The objective of the present study was to determine the prevalence of tobacco smoking in stabilized SZ outpatients and the clinical and treatment characteristics associated with daily tobacco use in a large community-dwelling sample of patients. Methods Three-hundred-and-sixty-one patients were included in the network of the FondaMental Expert Centers for Schizophrenia. Current tobacco status was self-declared. Results 53.7% were smokers. Mean age at tobacco onset was 17.2 years old. In multivariate analyses, after adjustment for confounding factors, positive symptoms and mean daily antipsychotic dose were associated with a higher frequency of tobacco use (OR = 1.06 95%IC[1.02–1.12], for positive symptoms, OR = 1.1, 95%IC[1.02–1.18] for daily antipsychotic dose). Education level, negative symptoms, anticholinergic agents, clozapine or aripiprazole administration were independently associated with a lower frequency of tobacco use (respectively OR = 0.87, 95%IC [0.79, 0.95], OR = 0.95, 95%IC[0.91–0.98], OR = 0.41, 95%IC[0.22–0.76], OR = 0.56, 95%IC = [0.32, 0.99] and OR = 0.49, 95%IC [0.26–0.91]). Conclusion The prevalence of current tobacco smoking in a French community-dwelling SZ patients is higher that observed in the general population. Patients with tobacco use present clinical and therapeutic specificities that may involve interaction between cholinergic-nicotinic and dopaminergic systems. The present study suggests that some therapeutics may improve daily smoking behavior in smokers. These results should be confirmed in longitudinal studies.

International audience; OBJECTIVES:Depression and negative symptoms have been associated with impaired Quality of life (QoL) in schizophrenia (SZ). However, childhood trauma may influence both QoL and depression in SZ patients, with consequences for the management of impaired QoL in SZ patients. The aim of the present study was to determine if childhood trauma was associated with impaired QoL in schizophrenia.METHOD:A sample of 544 community-dwelling stabilized SZ patients enrolled in FACE-SZ cohort were utilized in this study (74.1% males, mean aged 32.3years, mean illness duration 10.6years). QoL was self-reported with the S-QoL18 questionnaire. Childhood trauma was self-reported with the Childhood Trauma Questionnaire. Depression was measured by the Calgary Depression Rating Scale for Schizophrenia. Psychotic severity was measured by the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). Other clinical factors, treatments, comorbidities, functioning and sociodemographical variables were also recorded, with validated scales.RESULTS:Overall, 151 participants (27.8%) had a current major depressive episode and 406 (82.5%) reported at least one episode of historical childhood trauma. In multivariate analyses, lower QoL total score was associated with a history of childhood trauma (β=-0.21, p

Objectives Sex differences can yield important clues regarding illness pathophysiology and its treatment. Schizophrenia (SZ) has a lower incidence rate, and a better prognosis, in women versus men. The present study investigated the cognitive profiles of both sexes in a large multi-centre sample of community-dwelling SZ patients. Method 544 community-dwelling stable SZ subjects (141 women and 403 men; mean age 34.5 ± 12.1 and 31.6 ± 8.7 years, respectively) were tested with a comprehensive battery of neuropsychological tests. Results Although community-dwelling SZ men had more risk factors for impaired cognition (including first-generation antipsychotics administration and comorbid addictive disorders), women had lower scores on a wide range of cognitive functions, including current and premorbid intellectual functioning, working memory, semantic memory, non-verbal abstract thinking and aspects of visual exploration. However, women scored higher in tests of processing speed and verbal learning, as well as having a lower verbal learning bias. No sex difference were evident for visuospatial learning abilities, cued verbal recall, sustained attention and tests of executive functions, including cognitive flexibility, verbal abstract thinking, verbal fluency and planning abilities. Conclusion Sex differences are evident in the cognitive profiles of SZ patients. The impact on daily functioning and prognosis, as well as longitudinal trajectory, should be further investigated in the FACE-SZ follow-up study. Sex differences in cognition have implications for precision-medicine determined therapeutic strategies. Limits Given the restricted age range of the sample, future research will have to determine cognitive profiles across gender in late onset SZ.

The efficacy of using sonication (50 ± 0.2 W, 20 kHz), combined with subsequent concentration and storage at high osmotic pressure, has been evaluated to reduce levels of Salmonella bacteria in different solutions (PBS, sucrose and orange juice) at varying concentrations. To visualize the impact on cell membranes, we used a staining protocol (propidium iodide [PI] and 4′,6′-diamidino-2-phenylindole [DAPI]). Sonication alone did not cause significant membrane damage. Storage alone, for 48 h and at high osmotic pressure (10.9 MPa), affected membrane permeability in 20% of cells. However, sonication, combined with storage, considerably increased loss of membrane integrity, resulting in a significant logarithmic reduction of microorganisms. When the combination was applied to contaminated orange juice, a 5 log 10 cfu ml −1 reduction of Salmonella spp. was obtained. “Osmosonication”—the synergistic combination of sonication and subsequent storage at high osmotic pressure—is an innovative alternative for the non-thermal decontamination of liquid foods.

International audience; The main objective of this study was to determine the prevalence of akathisia in a community-dwelling sample of patients with schizophrenia, and to determine the effects of treatments and the clinical variables associated with akathisia. 372 patients with schizophrenia or schizoaffective disorder were systematically included in the network of FondaMental Expert Center for Schizophrenia and assessed with validated scales. Akathisia was measured with the Barnes Akathisia Scale (BAS). Ongoing psychotropic treatment was recorded. The global prevalence of akathisia (as defined by a score of 2 or more on the global akathisia subscale of the BAS) in our sample was 18.5%. Patients who received antipsychotic polytherapy were at higher risk of akathisia and this result remained significant (adjusted odd ratio=2.04, p=.025) after controlling the influence of age, gender, level of education, level of psychotic symptoms, substance use comorbidities, current administration of antidepressant, anticholinergic drugs, benzodiazepines, and daily-administered antipsychotic dose. The combination of second-generation antipsychotics was associated with a 3-fold risk of akathisia compared to second-generation antipsychotics used in monotherapy. Our results indicate that antipsychotic polytherapy should be at best avoided and suggest that monotherapy should be recommended in cases of akathisia. Long-term administration of benzodiazepines or anticholinergic drugs does not seem to be advisable in cases of akathisia, given the potential side effects of these medications.

Objective Abdominal obesity was suggested to be a better predictor than Metabolic Syndrome (MetS) for cardiovascular mortality, however this is has not been extensively studied in schizophrenia. Hyperuricemia (HU) was also suggested to be both an independent risk factor for greater somatic comorbidity and a global metabolic stress marker in patients with schizophrenia. The aim of this study was to estimate the prevalence of MetS, abdominal obesity and HU, to examine the association between metabolic parameters with HU in a cohort of French patients with schizophrenia or schizo-affective disorder (SZ), and to estimate the prevalence rates of treatment of cardio-vascular risk factors. Method 240 SZ patients (age = 31.4 years, male gender 74.3%) were systematically included. Metabolic syndrome was defined according to the International Diabetes Federation and HU if serum uric acid level was above 360 μmol/L. Results MetS, abdominal obesity and HU were found respectively in 24.2%, 21.3% and 19.6% of patients. In terms of risk factors, multiple logistic regression showed that after taking into account the potential confounders, the risk for HU was higher in males (OR = 5.9, IC95 [1.7–21.4]) and in subjects with high waist circumference (OR = 3.1, IC95 [1.1–8.3]) or hypertriglyceridemia (OR = 4.9, IC95 [1.9–13]). No association with hypertension, low HDL cholesterol or high fasting glucose was observed. Only 10% of patients with hypertension received a specific treatment, 18% for high fasting glucose and 8% for dyslipidemia. Conclusions The prevalence of MetS, abdominal obesity and hyperuricemia is elevated in French patients with schizophrenia, all of which are considerably under-diagnosed and undertreated. HU is strongly associated with abdominal obesity but not with psychiatric symptomatology.

In this study, the possibility of using low pressure hydrogenated steam, which is capable of reproducing similar oxidising electrochemical potentials, has been examined. The oxides formed between 350°C and 500°C in low pressure steam have been characterised and compared to oxide that formed in high pressure water in autoclave tests at 350°C. The comparison shows that the oxides formed are similar but not identical. However, constant load tests carried in hydrogenated steam at 400°C showed a similar trend to the classical dependency of PWSCC as a function of potential. The oxides formed in both environments were characterized via FIB and AEM techniques. At 500°C internal oxidation and preferential oxidation of grain boundaries was observed but only on samples that were prepared by OPS. Conversely, those samples ground to 600 grit revealed a continuous and protective oxide. At lower temperatures the internal oxidation was almost suppressed, although the effect of surface preparation was still present and had a clear influence on the SCC test carried out at 400°C. Cr-rich carbides in the alloy appeared to accelerate the oxidation in the both the bulk and along the grain boundaries. This was observed for both steam and autoclave-exposed specimens.AEM characterisation of the exposed specimens has been employed to determine the preferential oxidation rates and associated Cr depletion. The observed intergranular Cr-depletion was asymmetric and it was estimated that a two orders of magnitude difference in diffusivity were required to account for the observed difference.

Alloy 600 used as a material for steam generator tubings in pressurized water reactors is susceptible to intcrgranular stress corrosion cracking. Laboratory tests have shown that on tensile smooth specimens alloy 600 stress corrosion cracking in the thickness (1.27 mm) involved first an initiation period depending mainly on electrochemical processes, then a slow-propagation stage with crack depth less than a critical size—highly influenced by stress and mechanical state of the surface—and finally a rapid-propagation stage leading to failure. Tests separating stress and strain-rate contributions have shown that strain-rate is the most suitable parameter to describe the different stages of propagation. Stress is only needed to generate a creep rate. Correlation between SCC susceptibility and creep strain-rate was investigated at 360 °C on six mill-annealed tubes showing different chemical compositions, mechanical properties and grain sizes. The tubes with high creep strain-rate exhibited the greatest susceptibility to stress corrosion cracking and several tubes with low creep strain-rate demonstrated a low susceptibility, but one slow-creeping tube evidenced a relatively easy cracking. Heat treatment at 700 °C, which has resulted in an increased creep rate, was found to improve stress corrosion cracking resistance. This lack of correlation between creep and stress corrosion cracking may be a consequence of differences of metallurgical structure contribution to creep and (or) of an influence of primary water on the creep rate of alloy 600. An assessment of the durations of the initiation and the slow-propagation stages of cracking was attempted for the uniaxial tensile tests, using the macroscopic strain-rate. A crack-tip strain-rate damage model is still in progress to predict these durations for constant-load tests from constant extension rate tests (CERTs).

In France, most of the electricity produced is of nuclear origin. To produce this energy, Electricite de France has been operating for many years 56 pressurized water reactors with a permanent concern for safety efficiency and availability. These reactors consist of a main primary system which includes the reactor vessel, the steam generators, the pressurizer, and the reactor coolant pumps for flowing the coolant : the water. The heat produced by the fission reactions is collected through the steam generator by the secondary system where the steam produced is transformed into mechanical energy by a turbine which drives a generator producing the electrical energy.

The structural characterisation of Hydrogen Uranyl Phosphate (HUP) samples has been performed using both the powder X-ray diffraction and thermogravimetry techniques. The structural behaviour has been studied using either ageing or different drying process (temperature, vacuum, drying agents,…). Four main states of dehydration have been identified and the corresponding crystal cells are proposed. Parallel, X-ray and neutron diffraction as well as thermogravimetric analysis have been used in order to precise the location of protons in the pyrochlore-structured compound HSbTeO6·H2O. At the light of complementary properties, thermogravimetric and impedance spectroscopy have been performed on mixtures of the hereabove electrolytes. The measurements evidence a good ability of the mixtures to conciliate both a large level of conductivity and a rather fast reversibility of charge and discharge.

A R and D program is carried out in CEA and EDF laboratories to investigate separately the effects of factors which could contribute to IASCC mechanism. In the framework of this study, the influence of cold work on SCC of ASSs in primary water is studied to supply additional knowledge concerning the contribution of radiation hardening on IASCC of ASSs. Solution annealed ASSs, essentially of type AISI 304(L) and AISI 316(L), are generally considered very resistant to SCC in nominal primary water. However, Constant Extension Rate Tests (CERTs), performed on cold pressed humped specimens in nominal primary water at 360 deg. C, reveal that these materials can exhibit a high SCC susceptibility: deepest cracks reach 1 mm (mean crack growth rate about 1 {mu}m.h{sup -1}) and propagation is mainly intergranular for 304L and mainly transgranular for 316L. Indeed, work hardening in conjunction with high localized deformation can promote SCC. The influence of the nature of the cold work (shot peening, reaming, cold rolling, counter sinking, fatigue work hardening and tensile deformation) is investigated by means of screening CERTs performed with smooth specimens in 304L at 360 deg. C. For a given cold work hardening level, the susceptibility to crack initiation strongly depends on the cold working process, and no propagation is observed for a hardness level lower than 300 {+-}10 HV(0.49N). The propagation of cracks is observed only for dynamic loadings like CERT, traction/relaxation tests and crack growth rate tests performed with CT specimens under trapezoidal loading. Although crack initiation is observed for constant load and constant deformation tests, crack propagation do not seem to occur under these mechanical solicitations for 17000 hours of testing, even for hardness levels higher than 450 HV(0.49N). The mean crack growth rate increases when the hardness increases. An important R and D program is in progress to complement these results and to develop a SCC model for ASSs in primary water of PWR. (authors)

In 1991, a vessel head penetration was found leaking at Bugey 3 plant during the hydrotest. Metallurgical investigations confirmed that this problem was again related to primary water stress corrosion cracking of alloy 600. Moreover, the main crack initiated in the base metal of the penetration (alloy 600) has also propagated in the weld metal in alloy 182. More recently, stress corrosion cracking in alloy 182 has been found on welds of U.S. plants. SCC susceptibility of alloy 182 has been evidenced by several laboratories. In France, all original vessel heads using alloy 600 have been or will be replaced with penetrations in alloy 690 (with 30% chromium). With respect to substitution materials, ELECTRICITE DE FRANCE has undertaken a large R&D study focusing on the development of new weld metals. The aim of this study was to identify new materials that will be able to weld alloy 690. Weld metals containing 15 to 30% Chromium have been studied. This paper presents an overview of the main results obtained on 19% Cr, 26% Cr and 30% Cr alloys with respect to alloy 182 (15% Cr). Firstly, the weldability of weld metals has been studied focusing on the susceptibility to hot cracking. Secondly, the resistance to thermal ageing has been investigated in order to detect any long term ordering of the solid solution Ni-Cr that could induce embrittlement. Hardness tests, Charpy tests and resistivity measurements did not show any effect of ageing up to 60,000 hours at 360°C. Thirdly, stress corrosion cracking susceptibility in primary water at 360°C has been evaluated during constant load tests, RUB tests, slow strain rate tests. No cracking was observed on material containing more than 26% Cr for both initiation and propagation. Finally, a life assessment was performed for all weld materials with respect to alloy 182.Copyright © 2004 by ASME