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Background and importance In our psychiatric hospital, it is common to prescribe psychotropic medications such as neuroleptics. One side effect of this drug class is to induce QT prolongation. The more torsadogen drugs we prescribe, the more rhythmic cardiac disease, such as torsade de pointe, may occur. Our hospital drug formulary contains three highly torsadogen drugs: escitalopram, hydroxyzine and domperidone. They must be avoided in situations that may increase the risk of torsades de pointes, such as hypokalaemia, bradycardia and other drugs that induce QT prolongation. Aim and objectives To analyse prescriptions containing at least one of three highly torsadogen drugs and detect torsadogen risk situations. Material and methods We retrospectively analysed all prescriptions over 3 months containing at least one of our three highly torsadogen drugs. We also had access to biological results and bradycardia was mentioned in the patient medical file. For each prescription of one of these three drugs, we checked that no other torsadogen drugs was prescribed, and that there was no bradycardia or hypokalaemia. Results During our study period, among all 584 prescriptions, we found 28 containing at least one of our three highly torsadogen drugs, including 8 contraindications (CI) due to co-prescription with other torsadogen drugs: 13 prescriptions containing escitalopram with 2 CI, 10 prescriptions containing hydroxyzine with 2 CI and 5 prescriptions containing domperidone with 4 CI. For each of those 8 contraindications, a pharmacist intervention was redacted to stop the highly torsadogen drug prescription. Seven were accepted and followed and one was partially accepted. Of the total prescriptions, 11% contained drugs that might induce bradycardia and 53% contained drugs that might induce hypokalaemia. However, among 28 prescriptions containing our three highly torsadogen drugs, bradycardia and hypokalaemia were not found. Conclusion and relevance Prescribers may not know enough about the torsadogen risks of escitalopram, hydroxyzine and domperidone, with 80% of these prescriptions containing CI. The pharmacy intervention helped to avoid those 8 CI. This work reminds us to be vigilant about torsadogen drugs, providing many interactions. We regularly inform prescribers about drugs inducing QT prolongation, hypokalaemia or bradycardia to improve prescriptions. References and/or acknowledgements No conflict of interest.

RESUME La place de la France dans la realisation des essais cliniques a promotion industrielle recule depuis 10 ans. Les raisons en sont multiples : 1/ une diminution de l’offre therapeutique francaise liee a un recul de l’industrie pharmaceutique francaise qui n ‘a pas pris a temps le virage des biotechnologies, a la difficulte des Biotechs a atteindre une taille critique et des Medtechs a creer des leaders de taille mondiale. 2/ des lourdeurs administratives entrainant un retard des reponses de l’ANSM et des CPP aux procedures d’essais cliniques. 3/ une capacite d’inclusion insuffisante dans les delais impartis. 4 /une demotivation des investigateurs. A l’issue de ses auditions, le groupe de travail de l’Academie nationale de medecine formule des pistes de reflexion et une serie de propositions pour permettre a la France de retrouver son attractivite dans un domaine capital de l’innovation medicale pour le bien des patients.

Est-il possible et utile de comparer les cultures ludiques tangibles et intangibles de l’antiquité gréco-romaine et du monde rural nord-africain et saharien, deux mondes séparés par tant de siècles et différenciés par des milieux naturels et humains, des croyances, des coutumes et des organisations sociales spécifiques ? En élaborant ce document de travailje suis parti de l’hypothèse que cela pourrait être possible et suite à l’analyse des différences et similarités des jeux et jouets et de leur contexte matériel et socio-culturel j’ai remarqué plusieurs affinités tant dans leurs descriptions littéraires que dans les images

Is it possible and useful to compare the tangible and intangible play cultures of Greco-Roman antiquity and of the North African and Saharan rural world, two worlds separated by so many centuries and differentiated by natural and human environments, beliefs, customs and specific social organizations? In developing this working document I started from the assumption that it could be possible and following the analysis of the differences and similarities of play activities and toys and their material and sociocultural context I noticed several affinities proven both by literary descriptions and by images

This data article contains annotation data characterizing Multi Criteria Assessment (MCA) Methods proposed in the agri-food sector by researchers from INRA, Europe's largest agricultural research institute (INRA, http://institut.inra.fr/en). MCA can be used to assess and compare agricultural and food systems, and support multi-actor decision making and design of innovative systems for crop production, animal production and processing of agricultural products. These data are stored in a public repository managed by INRA (https://data.inra.fr/; https://doi.org/10.15454/WB51LL). Keywords: Literature search query, INRA divisions, Trade-offs, Multicriteria decision, Multicriteria assessment

L’espace alto-médiéval séparant Escaut et Rhin offre l’exemple d’une filiation territoriale entre Francia media (milieu du IXe siècle), Lotharingia (seconde moitié du IXe siècle) et Lothier (depuis les Xe-XIe siècles). La formation du Lothier est alors le fruit de la politique territoriale des empereurs de la dynastie saxonne. Le titre ducal qu’ils décernent à de grands féodaux chargés de les représenter et d’exercer des prérogatives déléguées par eux va bientôt subir un glissement qui l’affectera puis, par la force des choses, le circonscrira au seul Brabant (XIIe siècle). La référence au Lothier va toutefois survivre et être intégrée dans la titulature bien fournie des ducs Valois de Bourgogne, entrés au XVe siècle en possession du Brabant. On n’hésite pas alors, dans l’entourage de ces princes, à recourir à la fiction historique pour se remémorer la Lotharingie tout entière et à inspirer dans le même sens les récits de chroniqueurs et les pratiques héraldiques. Mais les gouvernants des Pays-Bas ne sont pas seuls à y être sensibles. La même référence tient aussi sa place dans le vocabulaire des gouvernés, brabançons en tout cas, aux temps modernes. La fiction ne va généralement pas jusqu’à compter le Lothier au nombre des « XVII Provinces » des souverains Habsbourg d’Espagne au XVIe siècle. Le souvenir en demeure néanmoins vivace au cœur du Roman Pays de Brabant, où vont le véhiculer jusqu’à la fin de l’Ancien Régime la mémoire d’un château disparu et la réalité d’une cour féodale, à l’appui de prétentions juridictionnelles. The alto-medieval area between Scheldt and Rhine is an example of a territorial affiliation between Francia media (middle of the ninth century), Lotharingia (second half of the ninth century) and Lothier (since the tenth and eleventh centuries). The creation of Lothier is then the result of the territorial policy of the emperors of the Saxon dynasty. The ducal title they award to feudal lords to represent them and exercise the powers delegated by them will soon undergo a shift that will affect and, by necessity, will circumscribe it to the Brabant (twelfth century). The reference to Lothier however will survive and be integrated into the great titular of the dukes Valois of Burgundy who came into possession of Brabant in the fifteenth century. There is no hesitation then in the environment of these princes, to use historical fiction to recall the whole Lotharingia and inspire in the same way the stories of the columnists and the heraldic practices. But the rulers of the Netherlands are not the only ones to be sensitive to it. The same reference also takes place in the vocabulary of the governed, in Brabant in any case, in the early modern eras. Generally the fiction doesn’t put Lothier in the number of the ’ XVII Provinces ’ of the Habsburg of Spain in the sixteenth century. The memory still remains alive in the heart of the Roman Pays de Brabant, which will convey it to the end of the Ancien Régime, as well as the memory of a vanished castle and the reality of a feudal court, in support of jurisdictional claims.

In Belgium, the health care financing system puts a pressure to reduce as much as possible the length of stay in all the acute care hospitals. Unfortunately, this system is mainly based on diagnoses (All Patients Refined Diagnostic Related Groups) and does almost not take into account the functional ability of the patients. Consequently, the neurologists try to discharge their stroke patients as soon as possible. The neurologists working in the acute hospital have then to collaborate with other facilities, usually independent from their institutions. If the patient returns to home, collaboration with the community-based care is required. If the patient is unable to return to home, he will be discharged to rehabilitation facilities or to a nursing home. Since several years, our Physical Medicine and Rehabilitation department have developed a close collaboration with the Neurology departments for two purposes. For one hand, to provide an early rehabilitation after stroke when the patient stay in the stroke unit. On the other hand, to help the neurologist to discharge the stroke patients by organizing their inpatient or outpatient rehabilitation. To optimize this organisation, we are trying to develop a Clinical Pathway. During this round table, I will share our daily clinical practice experience in this field.

Human locomotion is a rhythmic process whose variability can be investigated in two different ways. The magnitude of the stride duration fluctuation can be addressed by classical mathematical methods (coefficients of variation) and are usually computed on about ten cycles. Fluctuation dynamics between strides can be characterized using the autocorrelation function computed by combining analysis of the Hurst exponent and of power spectral density over a large number of consecutive cycles (>=512) (Crevecoeur, J Neurosci Methods 2010). These analyses show that stride duration does not fluctuate at random but in a very complex way. Indeed, consecutive strides are characterized by correlations that can span over a large number of strides reflecting a centrally controlled behavior. Long-range autocorrelations are present among stride duration variability on level ground and on treadmill (Bollens, Gait&Posture 2010). They are not influenced by gait speed and subject age whereas coefficients of variation were inversely related to walking speed and the age of the subjects (Bollens, Neuroscience 2012). Long-range autocorrelations seem robust, being influenced by neither dual task walking nor backward walking (Bollens, Ann Biomed Eng 2013). Fluctuation magnitude and dynamics could be complementary tools for more complete gait characterization, in research and in clinical practice.

Effects of microgravity (mG) on fertilization were studied in the urodele amphibian Pleurodeles waltl on board the MIR space station. Genetic and cytomorphologic analyses ruled out parthenogenesis or gynogenesis and proved that fertilization did occur in mG. Actual fertilization was demonstrated by the analysis of the distribution of peptidase-1 genes, a polymorphic sexlinked enzyme, in progenies obtained in mG. Further evidence of fertilization was provided by the presence of spermatozoa in the perivitelline space and in the fertilization layer of the mG eggs and by the presence of a female pronucleus and male pronuclei in the egg cytoplasm. Experiments in mG and in 1.4G, 2G, and 3G hypergravity showed for the first time that, compared to eggs in 1G, several characteristics of the fertilization process including the cortical reaction and the microvillus transformations were altered depending on the gravitational force applied to the eggs. Microvillus elevation, the most evident feature, was reduced on mG-eggs and amplified on eggs submitted to 2G and 3G. No lethal consequences of these alterations on the early development of mG-eggs were observed. developmental biology, fertilization

Anomalie m.p. is a spontaneous and heritable hindlimb abnormality described earlier. Twenty years later, Pleurodeles waltl larvae from the strain bearing anomalie m.p. and reared at room temperature or at 30 degrees C, expressed abnormalities (ectrodactylia, hemimelia, ectromelia). A morphological study of all the hindlimbs and an analysis of the hindlimb skeleton of samples from the experimental animals confirmed that most of the skeletal malformations were identical to those previously reported and affected the disto-proximal and prepostaxial pattern of the hindlimb. Analysis of the effects of rearing temperature on the expression of anomalie m.p. showed that the effects varied according to the developmental period at which the heat treatment was applied; the sooner the heat treatment began, the more numerous and more various were the degrees of severity of the malformations. Moreover, heat treatment induced the expression of two additional malformations not yet described: the first one, named 'reversed knee joint', was characterized by a reversal of the knee joint, and the second one, named 'twisted foot', by a downward twisting of the foot. The epigenetic effects of rearing at 30 degrees C on hindlimb development are discussed with regard to the differentiation or patterning.

The objective was to identify the mechanisms which contribute to the hypercoagulability associated with anti-phospholipid antibodies. Antibody-mediated platelet activation and interference of antibodies with phospholipid-dependent reactions were investigated. Murine monoclonal antibodies directed against ß2-glycoprotein I and prothrombin were used as model of anti-phospholipid antibodies. An anticoagulant effect, evidenced by impairment of thrombin generation and a procoagulant effect, by inhibition of activated protein C activity were shown. These phenomena occurs independently of platelet activation. The overall result was hypercoagulability. When immune-mediated platelet activation is sufficiently intense, it increases the amount of procoagulant phospholipids and antagonizes partially the anticoagulant effect of anti-phospholipid antibodies. Thus platelet activation contributes to reinforce the hypercoagulability due to activated protein C resistance. The antibody/antigen complexes interfere with pro- and anticoagulant complexes to the platelet surfaces. The avidity of each studied partners for the phospholipid surfaces take part in the mechanisms leading to hypercoagulability associated with antiphospholipid antibodies., L'objectif était d'identifier le ou le(s) mécanismes contribuant à l'hypercoagulabilité associée aux anticorps anti-phospholipides. L'activation plaquettaire induite par les anticorps ainsi que l'interférence des complexes anticorps/antigène avec les réactions dépendantes des phospholipides ont été étudiées. Des anticorps monoclonaux murins dirigés contre la ß2-glycoproteine I et la prothrombine ont été utilisés comme modèle des anticorps anti-phospholipides. Les résultats obtenus montrent que ces anticorps ont un effet anticoagulant qui se traduit par une diminution de la génération de thrombine et un effet procoagulant qui se traduit par une inhibition de l'activité de la protéine C activée. Ces anomalies surviennent indépendamment de l'activation plaquettaire. La résultante globale est une hypercoagulabilité. Une activation plaquettaire, suffisamment intense, augmente la quantité de phospholipides procoagulants et neutralise partiellement l'effet anticoagulant des anticorps anti-phospholipides. Ainsi, l'activation plaquettaire contribue à renforcer l'hypercoagulabilité due à la résistance à la protéine C activée. Les complexes anticorps/antigène interfèrent avec les complexes pro- et anticoagulants au niveau des surfaces plaquettaires. Les avidités respectives de chacun des partenaires étudiés pour les surfaces phospholipidiques participent aux mécanismes conduisant à l'hypercoagulabilité associée aux anticorps anti-phospholipides.

The objective was to identify the mechanisms which contribute to the hypercoagulability associated with anti-phospholipid antibodies. Antibody-mediated platelet activation and interference of antibodies with phospholipid-dependent reactions were investigated. Murine monoclonal antibodies directed against ß2-glycoprotein I and prothrombin were used as model of anti-phospholipid antibodies. An anticoagulant effect, evidenced by impairment of thrombin generation and a procoagulant effect, by inhibition of activated protein C activity were shown. These phenomena occurs independently of platelet activation. The overall result was hypercoagulability. When immune-mediated platelet activation is sufficiently intense, it increases the amount of procoagulant phospholipids and antagonizes partially the anticoagulant effect of anti-phospholipid antibodies. Thus platelet activation contributes to reinforce the hypercoagulability due to activated protein C resistance. The antibody/antigen complexes interfere with pro- and anticoagulant complexes to the platelet surfaces. The avidity of each studied partners for the phospholipid surfaces take part in the mechanisms leading to hypercoagulability associated with antiphospholipid antibodies., L'objectif était d'identifier le ou le(s) mécanismes contribuant à l'hypercoagulabilité associée aux anticorps anti-phospholipides. L'activation plaquettaire induite par les anticorps ainsi que l'interférence des complexes anticorps/antigène avec les réactions dépendantes des phospholipides ont été étudiées. Des anticorps monoclonaux murins dirigés contre la ß2-glycoproteine I et la prothrombine ont été utilisés comme modèle des anticorps anti-phospholipides. Les résultats obtenus montrent que ces anticorps ont un effet anticoagulant qui se traduit par une diminution de la génération de thrombine et un effet procoagulant qui se traduit par une inhibition de l'activité de la protéine C activée. Ces anomalies surviennent indépendamment de l'activation plaquettaire. La résultante globale est une hypercoagulabilité. Une activation plaquettaire, suffisamment intense, augmente la quantité de phospholipides procoagulants et neutralise partiellement l'effet anticoagulant des anticorps anti-phospholipides. Ainsi, l'activation plaquettaire contribue à renforcer l'hypercoagulabilité due à la résistance à la protéine C activée. Les complexes anticorps/antigène interfèrent avec les complexes pro- et anticoagulants au niveau des surfaces plaquettaires. Les avidités respectives de chacun des partenaires étudiés pour les surfaces phospholipidiques participent aux mécanismes conduisant à l'hypercoagulabilité associée aux anticorps anti-phospholipides.

In vertebrates, only few experiments have been performed in microgravity to study the embryonic development from fertilization. To date, these concern only amphibian and fish. We report here a study on the embryonic development of Pleurodeles waltl (urodele amphibian) eggs oviposited in microgravity. The experiment was performed twice on board the Mir space station and the data obtained included video recording and morphological, histological and immunocytological analyses. The data confirm that the microgravity conditions have effects during the embryonic period, particularly during cleavage and neurulation, inducing irregular segmentation and abnormal closure of the neural tube. Moreover, we observed several abnormalities hither to undescribed corresponding to cortical cytoplasm movements, a decrease of cell adhesion and a loss of cells. These abnormalities were temporary and subsequently reversible. The young larvae that hatched during the flight displayed normal morphology and swimming behavior after landing. The results obtained in the urodele Pleurodeles waltl are in accordance with those observed earlier in the anuran Xenopus laevis and in the fish Oryzias latipes.

The FERTILE experiment was twice performed onboard the Mir space station during the Cassiopee and Pegase French space missions. The goal was to analyze the effects of microgravity on fertilization and embryonic development, and then on further development on the ground in the amphibian Pleurodeles waltl. The present paper reports development that occurred in the laboratory after landing. Recovered on the ground at the hatching stage, young larvae reared at room temperature underwent metamorphosis and became adults without obvious abnormalities. Of particular interest was the rearing temperature that induced a delayed metamorphosis for animals from the Cassiopee space mission, but not for animals from the Pegase mission. The rate of development and the morphology were analogous in these animals and in ground controls reared in a similar annual period. Analysis of offspring was performed using these animals. Males born in space were first mated with control ground-born females and then with females born in space. The mating gave progeny that developed normally. Depending on the methods used and on the limits of the analyses, the results clearly demonstrated that animals born in space were able to live and reproduce after return to the ground.

Viable chimeras were constituted with two cranial and caudal complementary pieces of embryos derived from two distinct histocompatible AA and BB strains, which were incompatible with each other. The embryonic gonads of the resulting chimeras constituted two homo- or heterosexual territories. In most heterosexual chimeras, the testicular territory sex reversed the ovarian territory. The offspring analysis of a male chimera conclusively proved that ZW germ cells derived from the posterior female piece differentiated into spermatozoa. Nevertheless, the opposite situation was also demonstrated with a female chimera in which ZZ germ cells derived from the anterior male piece differentiated into oocytes. These gametogenesis reversions were tested by genetic and immunogenetic analyses of chimera offspring. The phenomenon of tolerance or rejection of skin allo- and autograft was used as a marker of origin of the chimera germ cells, which had produced the offspring. Moreover, in the first stage of the study, the origin of the pieces of adult chimeras was determined using skin grafts. During this stage, the embryonic tolerance was confirmed by the acquisition of four pieces of pairs of chimeras, and by the preservation of skin immunogenicity that was derived from each piece of the chimeras.

Effects of microgravity (microG) on fertilization were studied in the urodele amphibian Pleurodeles waltl on board the MIR space station. Genetic and cytomorphologic analyses ruled out parthenogenesis or gynogenesis and proved that fertilization did occur in microG. Actual fertilization was demonstrated by the analysis of the distribution of peptidase-1 genes, a polymorphic sex-linked enzyme, in progenies obtained in microG. Further evidence of fertilization was provided by the presence of spermatozoa in the perivitelline space and in the fertilization layer of the microG eggs and by the presence of a female pronucleus and male pronuclei in the egg cytoplasm. Experiments in microG and in 1.4G, 2G, and 3G hypergravity showed for the first time that, compared to eggs in 1G, several characteristics of the fertilization process including the cortical reaction and the microvillus transformations were altered depending on the gravitational force applied to the eggs. Microvillus elevation, the most evident feature, was reduced on microG-eggs and amplified on eggs submitted to 2G and 3G. No lethal consequences of these alterations on the early development of microG-eggs were observed.

The aim of the present study was to define the morphology and the crystallographic and chemical composition of otoconia in different regions of the inner ear in Pleurodeles waltl (urodele amphibian). The inner ear of adults was microdissected and otoconia were analyzed by scanning electron microscopy (SEM), X-ray diffraction, energy dispersive X-ray (EDX) and transmission electron microscopy. Two types of crystals were detected by SEM. Otoconia had different shapes depending on their location in the membranous labyrinth. One type had a cylindrical body with a triplanar smooth facet at each end, the other ones had either a prismatic shape with flat sides and end faces or a fusiform shape with rounded body and pointed end. The forms corresponded to those previously identified by other authors. These two types of otoconia had different X-ray diffraction patterns. The cylindrical otoconia were calcitic and located in the utricle, the other ones were aragonitic and located in the saccule, lagena and endolymphatic sac. An analysis by EDX indicated that both types of otoconia contained about 95% calcium with trace quantities of sodium, magnesium, phosphorus, sulfur, chlorine and potassium. Trace amounts of strontium was only found in the aragonitic otoconia.

Non disponible / Not available, L'histologie osseuse a fait d'incontestables progrès grâce à l'inclusionen résine plastique sans décalcification et à l'étude histomorphométriquedes paramètres dynamiques. Le but de ce travail est d'appliquer ces techniques à l'illustration de quelques aspects de la construction et de la reconstruction osseuses. La croissance de l'os de l'enfant est sous la dépendance de nombreuxparamètres. L'altération de l'un d'entre eux se traduit par un profil histomorphométrique en rapport avec son expression clinique. La consolidation des fractures diaphysaires constitue un retour à l'ostéogénèse. L'ossification du cal interne est endoconjonctive, celle du cal externe mixte endoconjonctive et endochondrale. La régénération osseuse en distraction procède d'un mécanisme différent : la zone centrale est fibreuse et subit l'ossification endoconjonctiveparallèlement à l'allongement. Les antimitotiques perturbent modérémentle processus ct'ostéogénèse.