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The Indian Ocean provides a source of salt for North Atlantic deep-water convection sites, via the Agulhas Leakage, and may thus drive changes in the ocean’s overturning circulation1–3. However, little is known about the salt content variability of Indian Ocean and Agulhas Leakage waters during past glacial cycles and how this may influence circulation. Here we show that the glacial Indian Ocean surface salt budget was notably different from the modern, responding dynamically to changes in sea level. Indian Ocean surface salinity increased during glacial intensification, peaking in glacial maxima. We find that this is due to rapid land exposure in the Indonesian archipelago induced by glacial sea-level lowering, and we suggest a mechanistic link via reduced input of relatively fresh Indonesian Throughflow waters into the Indian Ocean. Using climate model results, we show that the release of this glacial Indian Ocean salinity via the Agulhas Leakage during deglaciation can directly impact the Atlantic Meridional Overturning Circulation and global climate.

Abdominal compartment syndrome (ACS) is a rare but potentially fatal complication that can occur during hip arthroscopy. This usually occurs as a result of arthroscopic fluid passing into the retroperitoneal space through the psoas tunnel. From the retroperitoneal space, the fluid can then enter the intraperitoneal space through defects in the peritoneum. Previous studies have identified female sex, iliopsoas tenotomy, pump pressure, and operative time as potential risk factors for fluid extravasation. We present a method to measure intraoperative fluid deficit during hip arthroscopy to alert surgeons to possible ACS. Our proposed technique requires diligent intraoperative monitoring of fluid output through various suction devices, including suction canisters, puddle vacuums, and suction mats. The difference is then calculated from the fluid intake from the arthroscopic fluid bags. If the difference is greater than 1500 mL, then the anesthesiologist and circulating nurse are instructed to examine the abdomen for distension every 15 minutes. This, combined with other common symptoms such as hypotension and hypothermia, should alert the surgical team to the development of ACS. Despite limitations to this technique, this approach offers an objective method to calculate intra-abdominal fluid extravasation., Technique Video Video 1 Video depicts normal operating room workflow using various suction devices to collect arthroscopy irrigation fluid. This process occurs during each hip arthroscopy case in conjunction with the anesthesiologist, circulating nurse, and primary surgeon. The patient is positioned in the supine position with traction using a post. The image seen at 0:38 is a fluoroscopic anteroposterior image of the right hip. Please refer to Figure 1 for more details. The image seen at the 1:07 is a right hip viewed from the anterolateral portal. Please refer to Figure 2 for more details.

The Green Edge initiative was developed to investigate the processes controlling the primary productivity and fate of organic matter produced during the Arctic phytoplankton spring bloom (PSB) and to determine its role in the ecosystem. Two field campaigns were conducted in 2015 and 2016 at an ice camp located on landfast sea ice southeast of Qikiqtarjuaq Island in Baffin Bay (67.4797∘ N, 63.7895∘ W). During both expeditions, a large suite of physical, chemical and biological variables was measured beneath a consolidated sea-ice cover from the surface to the bottom (at 360 m depth) to better understand the factors driving the PSB. Key variables, such as conservative temperature, absolute salinity, radiance, irradiance, nutrient concentrations, chlorophyll a concentration, bacteria, phytoplankton and zooplankton abundance and taxonomy, and carbon stocks and fluxes were routinely measured at the ice camp. Meteorological and snow-relevant variables were also monitored. Here, we present the results of a joint effort to tidy and standardize the collected datasets, which will facilitate their reuse in other Arctic studies. The dataset is available at https://doi.org/10.17882/59892 (Massicotte et al., 2019a).

A simplified model, representing the dynamics of marine organic particles in a given size range experiencing coagulation and fragmentation reactions, is developed. The framework is based on a discrete size spectrum on which reactions act to exchange properties between different particle sizes. The reactions are prescribed according to triplet interactions. Coagulation combines two particle sizes to yield a third one, while fragmentation breaks a given particle size into two (i.e. the inverse of the coagulation reaction). The complete set of reactions is given by all the permutations of two particle sizes associated with a third one. Since, by design, some reactions yield particle sizes that are outside the resolved size range of the spectrum, a closure is developed to take into account this unresolved range and satisfy global constraints such as mass conservation. In order to minimize the number of tracers required to apply this model to an ocean general circulation model, focus is placed on the robustness of the model to the particle size resolution. Thus, numerical experiments were designed to study the dependence of the results on (i) the number of particle size bins used to discretize a given size range (i.e. the resolution) and (ii) the type of discretization (i.e. linear vs. nonlinear). The results demonstrate that in a linearly size-discretized configuration, the model is independent of the resolution. However, important biases are observed in a nonlinear discretization. A first attempt to mitigate the effect of nonlinearity of the size spectrum is then presented and shows significant improvement in reducing the observed biases. Fil: Gremion, Gwenaëlle. Institut des Sciences de la Mer de Rimouski; Canadá Fil: Nadeau, Louis Philippe. Institut des Sciences de la Mer de Rimouski; Canadá Fil: Dufresne, Christiane. Institut des Sciences de la Mer de Rimouski; Canadá Fil: Schloss, Irene Ruth. Ministerio de Relaciones Exteriores, Comercio Interno y Culto. Dirección Nacional del Antártico. Instituto Antártico Argentino; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; Argentina. Universidad Nacional de Tierra del Fuego. Instituto de Ciencias Polares, Recursos Naturales y Ambiente; Argentina Fil: Archambault, Philippe. Laval University; Canadá Fil: Dumont, Dany. Institut des Sciences de la Mer de Rimouski; Canadá

A newborn infant has an extraordinarily vulnerable and immature central nervous system, which is undergoing rapid structural and functional development. As these infants are pre-verbal and their neurological systems are immature, assessing accurately and treating effectively procedure-related pain is a significant challenge. The nociceptive signals caused by the pain are accompanied by changes in regional blood oxygenation and neuronal activity in the infant’s brain. In this study, we developed a dual-mode Near-Infrared Spectroscopy (NIRS) and electroencephalography (EEG) monitor that can measure regional brain oxygenation and neuronal activity concurrently (safe and non-invasive). The neuronal activity is measured by an innovative low-noise EEG amplifier in both conventional and ultra-low frequency bandwidths. This multimodal recording allows us to investigate the coupling of neuronal activity and the neurovascular system as never before. NIRS and EEG electrodes are miniaturized and unified in one sensor. This modification facilitates the use of a NIRS/EEG device for recording from neonatal subjects. Ten infants, born between 27-35 weeks gestational age, are being recruited from the NICU at BCWH. They are monitored during a single, routine blood draw required for clinical care. In this experiment, we investigate the change of cerebral hemodynamic across 3 phases of blood collection, baseline, heel lance, recovery. Variation of blood flow accompanied with the slow shift of EEG has been detected during the pain stimulus phase. Additionally, the increase of gamma-band correlated to a rise in blood flow is also observed

Introduction et but de l’etude La presence d’une denutrition est associee a un risque accru de complications post-operatoires. Des lors, l’identification precoce des patients a risque est fondamentale afin d’assurer une prise en charge adequate des l’admission en hospitalisation. Le but de la presente etude a ete d’evaluer systematiquement le risque nutritionnel lors d’une consultation et d’evaluer la faisabilite de planifier une prise en charge nutritionnelle en consultation avant intervention neurochirurgicale, gastro-enterologique, orthopedique ou de chirurgie plastique. Materiel et methodes Le score de risque nutritionnel NRS (poids, perte de poids, indice de masse corporelle (IMC), diminution des ingesta) a ete enregistre chez tous les patients vus en consultation preoperatoire entre juin et septembre 2018. Le service de dietetique a ete averti de la date d’admission des patients a risque de denutrition, et une prise en charge a ete planifiee. Resultats et analyse statistique Pendant les 14 semaines de l’etude, 186 patients ont ete evalues. Au total, 31 d’entre eux (16 %, IMC 24,8 ± 5,1, 19 femmes, moyenne de 68 ans (41–93 ans)) etaient a risque de denutrition (score NRS > 0) en raison d’une diminution de la prise alimentaire (22 patients), d’une perte de poids involontaire (17 patients), ou d’un IMC Conclusion Au vu des durees de sejour tres courtes et des intervalles de temps tres variables entre consultation et admission pour intervention programmee, l’enregistrement systematique d’un score de risque nutritionnel est souhaitable en preadmission. Notre audit de pratiques a montre que le depistage du risque nutritionnel est realisable en preadmission et permet d’instaurer une strategie nutritionnelle ciblee des l’admission du patient.

Duns Scotus was one of the most important thinkers of the entire scholastic period. Of Scottish origin, he was a member of the Franciscan order and undertook theological studies first at Oxford and later at Paris. He left behind a considerable body of work, much of which unfortunately was still undergoing revision at the time of his death. Notable among his works are questions on Aristotle’s Metaphysics, at least three different commentaries on the Sentences of Peter Lombard (the required text for a degree in theology) and a lengthy set of university disputations, the quodlibetal questions. A notoriously difficult and highly original thinker, Scotus was referred to as ‘the subtle doctor’ because of his extremely nuanced and technical reasoning. On many important issues, Scotus developed his positions in critical reaction to the Parisian theologian Henry of Ghent, the most important thinker of the immediately preceding generation and a severe Augustinian critic of Aquinas. Scotus made important and influential contributions in metaphysics, epistemology and ethics. In metaphysics, he was the first scholastic to hold that the concepts of being and the other transcendentals were univocal, not only in application to substance and accidents but even to God and creatures. In this, Scotus broke with the unanimous view based on Aristotle that being could not be predicated of both substance and accident, much less of, except by analogy, God and creature. Scotus argued in general that univocity was required to underwrite any natural knowledge of God from creatures or of substance from accidents. Given univocity, he concluded that the primary object of the created intellect was being, rejecting Aquinas’ Aristotelian view that it was limited to the quiddity of the sense particular and Henry of Ghent’s Augustinian view that it was God. That is, Scotus argues that even the finite intellect of the creature is by its very nature open to knowing all being. Scotus’ proof of the existence of God is the most ambitious of the entire scholastic period. Prior efforts at demonstrating the existence of God showed little concern with connecting the eclectic body of inherited arguments. Scotus’ proof stands apart as an attempt to integrate logically into a single demonstration the various lines of traditional argument, culminating in the existence of God as an actually infinite being. As a result, his demonstration is exceedingly complex, establishing within a sustained and protracted argument God as first efficient cause, as ultimate final cause and as most eminent being – the so-called triple primacy – the identity within a unique nature of these primacies, and finally the actual infinity of this primary nature. Only with this final result of infinity is Scotus prepared to claim he has fully demonstrated the existence of God. Notable features of the proof include Scotus’ rejection of Aristotle’s argument from Physics VIII (the favoured demonstration of Aquinas), the reduction of exemplar cause to a species of efficient cause, important clarifications about the causal relations at issue in arguments against infinite regress, an a priori proof constructed from the possibility of God similar to that proposed by Leibniz, and the rejection of the traditional argument that the infinity of God can be inferred from creation ex nihilo. Scotus is a realist on the issue of universals and one of the main adversaries of Ockham’s programme of nominalism. He endorsed Avicenna’s theory of the common nature, according to which essences have an independence and priority to their existence as either universal in the mind or singular outside it. Intepreting Avicenna, Scotus argued that natures as common must have their own proper unity which is both real and less than the numerical unity of a singular; that is, natures are common prior to any act of the intellect and possess their own real, lesser unity. They are accordingly not of themselves singular, but require a principle of individuation. Rejecting the standard views that essences are individuated by either actual existence, quantity or matter, Scotus maintained that the principle of individuation is a further substantial difference added to the species. This ‘individual difference’ is the so-called haecceitas or ‘thisness’, a term used seldom by Scotus himself. The common nature and individual difference were said by Scotus to be really identical in the individual, but ‘formally distinct’. The ‘formal distinction,’ developed by Scotus chiefly in connection with the Trinity and the divine attributes, is an integral part of his realism and was as such attacked by Ockham. It admits within one and the same thing a distinction between realities, formalities or entities antecedent to any act of the intellect to provide an objective foundation for our concepts. These formalities are nonetheless really identical and inseparably united within the individual. In epistemology, Scotus is important for his demolition of Augustinian illumination, at least in the elaborate defence of it given by Henry of Ghent, and the distinction between intuitive and abstractive cognition. Scotus rejected Henry’s defence as leading to nothing but scepticism, and set about giving a complete account of certitude apart from illumination. He grounded certitude in the knowledge of self-evident propositions, induction and awareness of our own states. After Scotus, illumination never made a serious recovery. Scotus’ other epistemological contribution was the allocation to the intellect of a direct, existential awareness of the intelligible object. This was called intuitive cognition, in contrast to abstractive knowledge, which seized the object independently of whether it was present to the intellect in actual existence or not. This distinction, credited to Scotus by his contemporaries, was invoked in nearly every subsequent scholastic discussion of certitude. While known primarily for his metaphysics, the importance and originality of Scotus’ ethical theory has been increasingly appreciated. Scotus is a voluntarist, holding for example that not all of the natural law (the decalogue) is absolutely binding, that prudence and the moral virtues are not necessarily connected and that the will can act against a completely correct judgment of the intellect. It is Scotus’ theory of will itself, however, that has attracted the most attention. He argues that the will is a power for opposites, not just in the sense that it can have opposite acts over time but in the deeper sense that, even when actually willing one thing, it retains a real, active power to will the opposite. In other words, he detaches the notion of freedom from those of time and variability, arguing that if a created will existed only for an instant its choice would still be free. In this, he has been heralded as breaking with ancient notions of modality that treated contingency principally in terms of change over time. Scotus argued that the will, as a capacity for opposites, was the only truly rational power, where the rational was opposed to purely natural agents whose action was determined. In this sense, the intellect, as a purely natural agent, was not a rational power. Finally, Scotus endowed the will with an innate inclination to the good in itself apart from any advantage it might bring to the agent. This inclination or affection for the just (affectio iustitiae, as it was termed by Anselm), enabled the will to escape the deterministic inclination of natures toward their own perfection and fulfilment.

International audience; PurposeStereotactic radiosurgery and hypofractionated stereotactic radiotherapy are standard treatments for brain metastases when they are small in size (at the most 3 cm in diameter) and limited in number, in patients with controlled extracerebral disease and a good performance status. Large inoperable brain metastases usually undergo hypofractionated stereotactic radiotherapy while haemorrhagic brain metastases have often been contraindicated for both stereotactic radiosurgery or hypofractionated stereotactic radiotherapy. The objective of this retrospective study was to assess a six 6 Gy-fractions hypofractionated stereotactic radiotherapy scheme in use at our institution for haemorrhagic brain metastases, large brain metastases (size greater than 15 cm3) or brain metastases located next to critical structures.Material and methodsPatients with brain metastases treated with the 6 × 6 Gy scheme since 2012 to 2016 were included. Haemorrhagic brain metastases were defined by usual criteria on CT scan and MRI. Efficacy, acute and late toxicity were evaluated.ResultsSixty-two patients presenting 92 brain metastases were included (32 haemorrhagic brain metastases). Median follow up was 10.1 months. One-year local control rate for haemorrhagic brain metastases, large brain metastases, or brain metastases next to critical structures were 90.7%, 73% and 86.7% respectively. Corresponding overall survival rates were 61.2%, 32% and 37.8%, respectively. Haemorrhagic complications occurred in 5.3% of patients (N = 5), including two cases of brain metastases with pretreatment haemorrhagic signal. Tolerance was good with only one grade 3 acute toxicity.ConclusionThe 6 × 6 Gy hypofractionated stereotactic radiotherapy scheme seems to yield quite good results in patients with haemorrhagic brain metastases, which must be confirmed in a prospective way.; Objectif de l’étudeLa radiochirurgie et la radiothérapie stéréotaxique sont le standard de traitement des métastases cérébrales lorsqu’elles sont peu nombreuses, de petite taille, chez les patients en bon état général et à la maladie extracérébrale contrôlée. Les métastases plus volumineuses sont souvent acceptées en stéréotaxie, tandis que les métastases hémorragiques restent plutôt contre-indiquées pour ce type de traitement. L’objectif de cette étude rétrospective était de rapporter les résultats obtenus par un schéma de fractionnement 6 × 6 Gy utilisé dans notre centre pour les métastases hémorragiques, de plus de 15 cm3 ou situées proches de structures à risque.Matériel et méthodesLes patients traités par ce schéma dans notre centre de 2012 à 2016 ont été inclus. Le caractère hémorragique était défini sur l’imagerie scanographique et IRM. L’efficacité et la tolérance ont été évaluées.RésultatSoixante-deux patients atteints de 92 métastases (32 hémorragiques) ont été inclus. Le suivi médian était de 10,1 mois. Le taux de contrôle local à 1 an pour les métastases hémorragiques, les grosses métastases, et les métastases proches de structure à risque étaient respectivement de 90,7 %, 73 % et 86,7 %. Les taux correspondants de survie globale étaient de 61,2 %, 32 % et 37,8 %. Des complications hémorragiques ont été observées chez 5,3 % des patients (deux lésions hémorragiques avant le traitement). Un seul cas de toxicité aiguë de grade 3 a été observé, résolutif après traitement symptomatique.ConclusionLe Schéma 6 × 6 Gy semble réalisable et plutôt efficace en traitement des métastases hémorragiques, ce qui reste à confirmer en prospectif.

The use of phenoxy nanocomposite films as carriers of nanofillers involving multiwalled carbon nanotubes and nanoclays is successfully demonstrated for application in epoxy carbon fibers reinforced composites (CFRC) processed by RTM. Model studies on individual nanocomposite filaments embedded in epoxy precursors show that the nanofillers are passively transported by the interdiffusion gradient during heating over distance around 800 lm. A morphology gradient is generated after reaction induced phase separation and the nanofillers end up in the epoxy, despite their initial dispersion in the phenoxy. The proof of concept is extended to CFRC panels where nanocomposite phenoxy films are prepositioned between every odd carbon layer of the preform. Carbon nanotubes are filtered by the carbon fabrics, which limits their full diffusion and that of phenoxy through the preform. This has negative consequences on fracture toughness (GIc). For nanoclay, GIc is rather slightly improved although the origin is not fully clear.

We explore the influence of the interdiffusion of two thermoplastic tougheners and RTM6 epoxy resin precursors on the resulting morphologies after curing and the consequences on delamination toughness of the corresponding carbon fiber reinforced composites. Two thermoplastics with contrasting Tg and compatibility, i.e. poly(ether sulfone) (PES) and phenoxy are compared. The dramatic improvement of the interlaminar fracture toughness (GIC) found for the phenoxy-RTM6 system as compared to the pure thermoset reference can be ascribed to the broad morphology gradient only observed for that system. By contrast, the PES-RTM6 system is characterized by a steep morphology gradient and a corresponding decrease of as compared to the reference.

Instability of the hip can manifest in a wide range of settings, with presenting symptoms including subtle discomfort at end range of motion or more dramatic dislocation of the joint. It can result from traumatic injury with dislocation or subluxation; atraumatic capsular laxity; structural bony abnormality, such as acetabular dysplasia; and iatrogenic injury. Initial treatment of the concentrically reduced joint often begins with physical therapy to strengthen dynamic stabilizers and to allow time for resolution of acute symptoms. Surgical treatment is aimed at repairing injured soft tissue structures, including static stabilizers, and addressing underlying bony structural deficiencies.

Toughening of epoxy thermosets with thermoplastics is an important avenue towards improved properties of high-performance systems. The main focus of the work reported was to study the complex issue of interdiffusion between thermoplastics and epoxy resin precursors, using a combination of experimental and numerical simulation methods, in order to understand the key parameters driving the process. Diameter changes of thermoplastic filaments in contact with epoxide and diamine precursors have been followed and an original approach using carbon nanotubes as tracers of the filament swelling front has been developed. This method shows that the improved mobility of low-molecular-weight resin monomers as well as the greater mobility of phenoxy of lower glass transition temperature as compared to poly(ether sulfone) control dissolution by favouring the penetration of precursors into the thermoplastic and lead to both swelling of the outer part of the filaments and reduction of the inner unaffected core. Simulation by molecular dynamics supports the idea that diffusion of polymer macromolecules remains limited compared to the dominant effect of precursor diffusion. Indeed, low diffusion coefficients have been predicted for thermoplastic oligomers compared to resin monomers. For the latter, the calculated values correlate well with the experimental data measured during interdiffusion

This article reviews three attempts at pension restructuring in France: the 1993 Balladur Reform, the 1995 Juppe Plan and the 2003 Raffarin Reform. It argues that most academic accounts place undue emphasis on elite-level interaction in the policymaking process instead of focussing on the ways in which such interaction is decisively shaped by tensions within the labour movement. Specifically, trade-union leaders confront the government as members of the labour bureaucracy – a contradictory social stratum which seeks to reconcile the antagonistic interests of its working-class base with the exigencies of capital and the state. Insofar as it performed a social control function during socio-political crises threatening to derail pension reform, the labour bureaucracy acted in ways that are not easily explained by standard theoretical models.

Resume Objectif L’evaluation des risques chimiques professionnels en etablissement de sante est complexe et doit repondre a de nombreuses obligations reglementaires. L’objectif de ce travail est de valider des guides et methodes d’aide a l’evaluation des risques chimiques qui soient adaptes aux specificites des etablissements de sante. Methode Au sein du reseau national hospitalo-universitaire de medecine du travail, la methode d’evaluation des risques chimiques developpee est validee par son application simultanee dans les laboratoires d’hematologie de cinq CHU. Un logiciel d’aide a l’evaluation des risques est egalement teste et utilise comme outil d’echanges de donnees entre etablissements. Resultats La methode d’evaluation, basee sur la hierarchisation des risques chimiques par types d’effet et voies d’entree dans l’organisme, est validee dans le secteur des laboratoires. L’etude menee en laboratoires d’hematologie permet la caracterisation des produits dangereux et des situations de travail a risque, lesquelles sont relativement limitees eu egard aux faibles quantites manipulees et a l’automatisation de nombreuses analyses. Les principaux produits dangereux identifies font l’objet de l’edition de fiches de toxicite incluant les principales informations cliniques, techniques et reglementaires importantes pour les utilisateurs. Le logiciel valide permet la saisie de la toxicite des substances, la tracabilite des expositions professionnelles et l’edition automatisee de rapports d’evaluation. Un module de formation aux risques chimiques est cree afin de pallier le manque de connaissances sur ce risque constate au cours de l’etude. Conclusion Les differents outils crees doivent permettre de faciliter les demarches locales d’evaluation des risques chimiques en etablissements de sante. Les echanges sur ce theme dans le cadre de reseaux interetablissements apparaissent primordiaux afin de mutualiser les competences et les informations en la matiere.

Resume Objectif de l’etude Determiner la prevalence et analyser les caracteristiques generales des epileptiques au travail employes dans des entreprises en milieu urbain de la Republique du Benin. La situation de l’epilepsie dans le milieu professionnel beninois a ete tres peu exploree et aucune etude epidemiologique n’a ete realisee pour evaluer l’accessibilite des epileptiques au monde du travail. Methodes Une enquete transversale a ete realisee entre novembre 1999 et mai 2000 dans 5 entreprises volontaires installees dans 3 departements du sud du Benin et employant 4 584 salaries. Un sondage aleatoire, simple, proportionnel a la taille de chaque entreprise, a permis la constitution de l’echantillon. Le depistage de l’epilepsie a ete realise a partir du questionnaire d’investigation de l’epilepsie en zones tropicales. L’epilepsie etait confirmee par un neurologue. Des donnees socioprofessionnelles ont ete collectees pour chaque salarie. Resultats Dans cette etude, 1 232 salaries ont ete inclus, 46 etaient suspects d’epilepsie et 13 ont ete confirmes comme atteints d’epilepsie par le neurologue. La prevalence de l’epilepsie etait de 10,6 % (IC95% : 5,9-18,5). L’epilepsie etait active pour 9 sujets. Les crises d’epilepsie etaient constamment generalisees. Sept employes avaient debute leurs crises avant l’embauche dans l’entreprise (53,8 %) et aucun ne l’avait declare a l’employeur. Aucune difference avec les autres salaries n’etait retrouvee, a part le travail poste. Discussion Cette etude a permis de mettre en evidence que les epileptiques etaient presents dans les entreprises du Sud-Benin avec une frequence proche de celle retrouvee dans la population generale. Les caracteristiques socioprofessionnelles des salaries epileptiques beninois, en comparaison avec la population salariale, n’etaient pas significativement differentes.

© 2015 Macmillan Publishers Limited. All rights reserved. Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

There is limited data regarding the benefit of using an occlusal device to help patients resolve a variety of symptoms involving temporomandibular disorder, as well as head, neck, and shoulder pain. The purpose of this study was to evaluate the effect of a carefully adjusted occlusal device on 12 symptoms to determine if there was enough evidence to justify a randomized control trial of this methodology. Splints were designed to ensure a stable, reproducible, mandibular position in a cohort of 157 dental patients with mixed histories of the following 12 symptoms: temporomandibular joint "pop," "click," and lock; jaw, neck, shoulder, and mouth-opening pain; headache; earache; tinnitus; and clenching and grinding of teeth. The results showed significant improvement (P0.001) in 11 of the 12 symptoms.

Resume Contexte En France, l’incidence des lymphomes malins non-hodgkiniens (LMNH) a ete multipliee par deux et demi entre 1978 et 2000. Cette augmentation reste largement inexpliquee et l’implication de facteurs de risque d’origine environnementale et professionnelle est fortement suspectee. Objectif de l’etude Rechercher l’existence d’une relation entre certaines expositions environnementales liees a l’activite professionnelle ou aux habitudes de vie et la survenue de LMNH. Methodes Une etude cas-temoins apparies a ete menee au CHU de Limoges. Les cas de LMNH etaient recrutes dans le service d’hematologie et le diagnostic etait confirme par un examen histopathologique. Les temoins etaient recrutes dans le departement de sante au travail et etaient indemnes d’hemopathie maligne. Chaque cas etait apparie a deux temoins sur l’âge (± 5 ans) et le sexe. Le recueil des donnees (demographiques et antecedents, description des cas de LMNH, expositions) a ete realise grâce a un questionnaire standardise. Resultats Au total, 75 triplets ont ete inclus dans cette etude (75 cas et 150 temoins). L’analyse multivariee, utilisant un modele logistique, a permis de mettre en evidence que le risque ajuste de survenue de LMNH etait significativement associe a l’habitat a proximite d’une ligne a haute tension (OR = 4,5 ; IC 95 % : 2,1-9,5), a la consommation d’alcool (OR = 2,8 ; IC 95 % : 1,1-7,1), chez les travailleurs de la metallurgie (OR = 14,3 ; IC 95 % : 1,5-142,9), chez les travailleurs de la filiere du bois (OR = 5,9 ; IC 95 % : 1,2-28,6) et chez les travailleurs exposes a l’amiante (OR = 4,0 ; IC 95 % : 1,1-14,1). Discussion Pour expliquer cette sur-incidence des LMNH et compte tenu des resultats preliminaires de cette enquete, une structure regionale de reference va etre mise en place pour faciliter les etudes concernant le role des expositions professionnelles dans la survenue des LMNH et plus generalement l’epidemiologie de cette hemopathie maligne.

The degree of realism that Duns Scotus understood his formal distinction to have implied is a matter of dispute going back to the fourteenth century. Both modern and medieval commentators alike have seen Scotus's later, Parisian treament of the formal distinction as less realist in the sense that it would deny any extra-mentally separate formalities or realities. This less realist reading depends in large part on a question known to scholars only in the highly corrupt edition of Luke Wadding, where it is printed as the first of the otherwise spurious Quaestiones miscellaneae de formalitatibus. The present study examines this question in detail. Cited by Scotus's contemporaries as the Quaestio logica Scoti, we establish that it was a special disputation held by Scotus at Paris in response to criticisms of his use of the formal distinction in God, identify its known manuscripts, and provide an analysis based upon a corrected text, showing in particular the total unreliability of the Wadding edition. Our analysis shows that the Logica Scoti does not absolutely prohibit an assertion of formalities as correlates of the formal distinction, even in the divine Person, so long as their non-identity is properly qualified. That is, the positing of formalities does not of itself entail an unqualified or absolute distinction.

A model is proposed, which predicts the toughness of 7000 series aluminium alloys in a variety of situations, including two alloy compositions, different quench rates from the solution treatment temperature and ageing states from underaged to overaged. The model is derived in three steps. The energy dissipated by transgranular fracture is first calculated, using a simplified cohesive zone approach. The energy dissipated by intergranular fracture is then calculated using a critical strain criterion, and the total dissipated energy is then estimated using an averaging by the respective area fractions of the two modes, which are themselves dependent on the respective energies of the two main fracture mechanisms. The model input parameters are the material's mechanical properties such as yield stress and strain-hardening rate, geometrical features and related properties of the precipitate-free zones, and area fraction of the grain boundaries covered with precipitates. The model predicts all the main features of the evolution of the toughness/yield strength compromise with changing quench rate or ageing treatment. It allows to predict the evolution of toughness when dramatic changes in the occurrence of fracture modes are observed. Finally, using the model it is possible to predict the effect of changes in individual parameters on the overall fracture behaviour.

This paper investigates the precipitation microstructures in aluminium alloys 7040 and 7050 (Al - Zn - Mg - Cu variants) as a function of quench rate and aging treatment, and the associated compromise between yield strength and fracture toughness. The precipitate microstructures are quantitatively characterised by a combination of techniques covering the different scales involved: transmission electron microscopy (TEM), field emission gun scanning electron microscopy (FEG-SEM) and small angle X-ray scattering (SAXS), and fracture toughness is estimated using the Kahn tear test. Yield strength and strain hardening behaviour are determined by conventional tensile tests. It is shown that the composition modification from alloy 7040 to alloy 7050 results in a better compromise between yield strength and toughness. The strength decrease in alloy 7040 following a slow quench is much reduced compared to alloy 7050 because of a lower sensitivity to quench-induced precipitation on dispersoids. Both alloys...

Introduction La presence de synovite au cours du syndrome de Goujerot-Sjogren primitif est rare. L’objectif de cette etude etait de decrire la presentation et l’evolution sous traitement des patients suivis pour un syndrome de Goujerot-Sjogren primitif avec une atteinte articulaire et au moins une synovite. Patients et methodes Nous avons mene une etude retrospective, multicentrique, francaise, incluant les patients adultes suivis pour un syndrome de Goujerot-Sjogren primitif (criteres AECG), avec presence d’au moins une synovite clinique au cours du suivi. Les caracteristiques clinico-biologiques au moment du diagnostic de l’atteinte articulaire, la prise en charge therapeutique et l’evolution ont ete recueillies. La reponse therapeutique etait definie par la disparition de l’ensemble des synovites avec diminution ou disparition de l’ensemble des arthralgies. Resultats Entre 1998 et 2015, 57 patients dont 53 femmes (93 %) ont ete identifies dans 12 centres francais. Au moment du diagnostic de l’atteinte articulaire, l’âge median etait de 54 ans (45–63 ans), les patients avaient 8 articulations douloureuses (extremes : 4–12) et 4 articulations gonflees (extremes : 2–6). Le diagnostic de synovite etait clinique pour 65,3 % des patients ; 44,7 % des patients ont eu une confirmation de leurs synovites par echographie ou IRM. Au moment du diagnostic, la concentration serique de proteine c-reactive etait de 5 mg/L (3–9,3 mg/L). Des facteurs rhumatoides et des anticorps anti-CCP etaient retrouves chez respectivement 44,9 % et 13,7 % des patients. Aucun patient n’avait d’erosion radiographique. Le score ESSDAI etait a 7 (5–9). Tous les patients ont recu au moins une ligne therapeutique, 31 patients ont recu une seconde ligne therapeutique (54 %)et 13 une troisieme ligne therapeutique (23 %), representant en tout 101 lignes therapeutiques. Sur l’ensemble de ces lignes, les corticoides etaient utilises a 78 reprises (77,2 %), avec une dose mediane de 10 mg/j (7–12,5 mg/j), l’hydroxychloroquine dans 57 cas (57 %) a la dose de 400 mg/j, le methotrexate dans 44 cas (44 %) a la dose de 15 mg/semaine (15–20 mg/semaine). Le rituximab a ete utilise dans 19 cas (18,8 %) et les anti-TNF-α dans 4 cas (4 %). L’hydroxychloroquine seule permettait d’obtenir une reponse therapeutique articulaire dans 30,3 % des cas et dans 60,6 % des cas en cas d’association avec les corticoides. Le methotrexate seul ou en association avec l’hydroxychloroquine permettait d’obtenir une reponse articulaire dans 40,2 % et 57,1 % des cas respectivement, alors que 73,7 % des patients traites par rituximab presentaient une reponse clinique. Au cours d’un suivi median de 3 ans (1–6 ans), aucun patient n’a developpe d’erosion ou de destruction articulaires. Aux dernieres nouvelles, 44 patients etaient consideres comme repondeurs sur le plan articulaire (84,6 %), avec un score ESSDAI median de 3 (1–6) ; 11 patients (19,3 %) recevaient toujours des corticoides a 7 mg/j (5–10 mg/j). La contentration serique de proteine c-reactive etait de 3 mg/L (1,4–5 mg/L). Conclusion L’atteinte articulaire du syndrome de Goujerot-Sjogren primitif peut se presenter sous la forme de synovites qui sont non destructrices. Alors que le methotrexate, l’hydroxychloroquine et le rituximab semblent avoir une certaine efficacite, la meilleure strategie therapeutique reste a determiner.

The effect of process parameters such as quench rate and precipitation heat treatment on the compromise between the toughness and the yield strength of AA7050 aluminum alloy (AlZnMgCu) are investigated, as well as the anisotropy of this compromise in the rolling plane. Fracture toughness is experimentally approached by the Kahn tear test. The microstructure is studied quantitatively in detail by a combination of scanning electron microscopy, transmission electron microscopy and small-angle X-ray scattering, and the relative fractions of the various fracture modes as a function of microstructural state are quantitatively determined on scanning electron microscopy images. Toughness is confirmed to be minimum at peak strength, and lower for an overaged material than for an underaged material of the same yield strength. A lower quench rate is shown to result in an overall reduction of toughness, and in a reduced evolution of this toughness during the aging heat treatment. The overall toughness is also lowered when the main crack propagation direction is parallel to the preferential elongation direction of the coarse constituent particles (rolling direction). The competition between intergranular and transgranular fracture is explained in terms of the modifications of the work hardening rate, and of grain boundary precipitation. The evolution of fracture toughness is qualitatively explained in terms of evolution of yield stress, strain hardening rate, grain boundary precipitation and intragranular quench-induced precipitates.

The competition between intergranular and intragranular fracture is investigated using a bilayer damage model, which incorporates the relevant microstructural features of aluminium alloys with precipitate free zones (PFZ) nearby the grain boundary. One layer represents the grain behaviour: due to precipitation, it presents a high yield stress and low hardening exponent. The other layer represents the PFZ which has the behaviour of a solid solution: it is much softer but with a much higher strain hardening capacity. In both layers, void growth and coalescence is modelled using an enhanced Gurson-type model incorporating the effects of the void aspect ratio and of the relative void spacing. The effects on the ductility (i) of the flow properties of each zone, (ii) of the relative thickness of the PFZ, and (iii) of the particles spacing and volume fraction in the PFZ are elucidated. Comparisons are made with experimental data. Based on the previous analysis, qualitative understanding of trends in the fracture toughness of aluminium alloys can be gained in order to provide a link with the thermal treatment process. (C) 2003 Elsevier Science Ltd. All rights reserved.

The paper recalls the definition of alternated n-anagrams and the way to determine their total number a(n). Two devices are introduced to generate ‘composed’ anagrams and to calculate the numbers b(n) and c(n) of ‘indecomposable’ n-anagrams according to these devices; moreover three arithmetical properties of a(n), b(n) and c(n) are proved.

The infrared and Raman spectra (frequencies and intensities) of polydichloro-phosphazene are calculated with the help of molecular dynamics methods; the spectral patterns are analysed in relation to the bond conformations along the backbone. The application of a longitudinal stress to the polymeric chains and the corresponding spectral variations are simulated by the use of an expanded simulation box.

Molecular dynamics (MD) is a common and powerful method to simulate chemical systems at the atomic level. The calculation of vibrational spectra is a less common application of MD simulations. In this work, the interest was focused on the analysis of vibrational spectra (infrared and Raman) of polymers from MD data. For this purpose two methods were developed: the simulation of polarized IR spectra (IR dichroism) and the spectra of particular internal coordinates. Molecular dynamic calculations reproduce the polarized infrared spectra with a high accuracy in comparison with experimental data. It is shown that these data can be obtained from an analysis of the three-dimensional orientation of the molecular dipole moment. The calculated spectrum of any particular coordinate yields a direct correlation between a vibrational band and the concerned coordinate. We find an excellent agreement between these calculated spectra for polyethylene and the potential energy distribution (PED) derived from NCA. These spectra allow a quick assignment of vibrational bands also for IR or Raman inactive modes, which are found in power spectrum. Thus, MD is shown to be a method complementary to NCA.

This paper summarizes the results of a molecular dynamics study of the clathrate silicate dodecasil 3C with different methane fillings, which covered the influence of cavities on the behaviour of entrapped molecules. The simulations treat all degrees of freedom of methane at room temperature. The dynamics of methane is influenced very little by use of a flexible silicate framework, as compared with use of a rigid one. The calculated infrared and Raman spectra show that two types of molecular environment can be clearly recognized from the vibrational behaviour of the molecules. Also, in the low-frequency region the rigid molecule motions are well differentiated. In small cages the molecules are located near the centres of cages, whereas in large cages the molecules move along the walls of the cavities while their orientation is nearly free.

The dynamics of methane molecules encapsulated in the cages of dodecasil 3C (D3C) is studied by the molecular dynamics technique assuming that the silicate network is rigid. In both types of cages the molecular motion can be understood as a gliding of the molecules along the walls of the cages. This leads to low frequency motions characteristic of each cage.

Recent epidemiological studies have brought to light a possible link between premalignant or neoplastic skin lesions (Bowen disease, squamous carcinoma) and occupational exposure to 4,4′-bipyridyl (4,4′B), a precursor in the synthesis of paraquat herbicide. The present study used a serum-free cell culture of normal human keratinocytes (NHK) and two skin-equivalent models to test the effects of exposure to different concentrations of 4,4′B. Cytotoxicity of 4,4′B on NHK was measured by neutral red release assay. Superoxide dismutase (SOD) activity and cell cycle were analyzed in exposed and nonexposed NHK cultures. Histological and immunohistological tests enabled evaluation of differentiation and proliferation effects in reconstructed-skin models. Results showed that significant cytotoxicity occurred after 5 to 11 days' exposure to 4,4′B concentrations of 10-6-10-3 mol/L (IC50 between 10-3 and 10-4 mol/L 4,4′B after 11 days). Parallel modifications of SOD activity were recorded. Histological and immunohistological analysis revealed dose-related 4,4′B effects in reconstructed skin models. This involved abnormal terminal differentiation, connected with filaggrin expression, observed in skin models exposed to 10-7 and 10-6 mol/L 4,4′B. However, no modification of cell cycle or dysplasia was detected as a result of exposure to 4,4′B. Thus, 4,4′B appears to be cytotoxic for NHK, but as an isolated contaminant, and is unable to induce keratinocyte dysplasia in vitro. These preliminary results do not exclude a cocarcinogenic action of 4,4′B (with UVB for example).