Indirect comparison meta-analysis of two enoxaparin regimens in patients undergoing major orthopaedic surgery. Impact on the interpretation of thromboprophylactic effects of new anticoagulant drugs.

Two enoxaparin dosage regimens are used as comparators to evaluate new anticoagulants for thromboprophylaxis in patients undergoing major orthopaedic surgery, but so far no satisfactory direct comparison between them has been published. Our objective was to compare the efficacy and safety of enoxaparin 3,000 anti-Xa IU twice daily and enoxaparin 4,000 anti-Xa IU once daily in this clinical setting by indirect comparison meta-analysis, using Bucher's method. We selected randomised controlled trials comparing another anticoagulant, placebo (or no treatment) with either enoxaparin regimen for venous thromboembolism prophylaxis after hip or knee replacement or hip fracture surgery, provided that the second regimen was assessed elsewhere versus the same comparator. Two authors independently evaluated study eligibility, extracted the data, and assessed the risk of bias. The primary efficacy outcome was the incidence of venous thomboembolism. The main safety outcome was the incidence of major bleeding. Overall, 44 randomised comparisons in 56,423 patients were selected, 35 being double-blind (54,117 patients). Compared with enoxaparin 4,000 anti-Xa IU once daily, enoxaparin 3,000 anti-Xa IU twice daily was associated with a reduced risk of venous thromboembolism (relative risk [RR]: 0.53, 95% confidence interval [CI]: 0.40 to 0.69), but an increased risk of major bleeding (RR: 2.01, 95% CI: 1.23 to 3.29). In conclusion, when interpreting the benefit-risk ratio of new anticoagulant drugs versus enoxaparin for thromboprophylaxis after major orthopaedic surgery, the apparently greater efficacy but higher bleeding risk of the twice-daily 3,000 anti-Xa IU enoxaparin regimen compared to the once-daily 4,000 anti-Xa IU regimen should be taken into account.

Extracellular Subunit Interactions Control Transitions between Functional States of Acid-sensing Ion Channel 1a.

Acid-sensing ion channels (ASICs) are neuronal, voltage-independent Na(+) channels that are transiently activated by extracellular acidification. They are involved in pain sensation, the expression of fear, and in neurodegeneration after ischemic stroke. Our study investigates the role of extracellular subunit interactions in ASIC1a function. We identified two regions involved in critical intersubunit interactions. First, formation of an engineered disulfide bond between the palm and thumb domains leads to partial channel closure. Second, linking Glu-235 of a finger loop to either one of two different residues of the knuckle of a neighboring subunit opens the channel at physiological pH or disrupts its activity. This suggests that one finger-knuckle disulfide bond (E235C/K393C) sets the channel in an open state, whereas the other (E235C/Y389C) switches the channel to a non-conducting state. Voltage-clamp fluorometry experiments indicate that both the finger loop and the knuckle move away from the β-ball residue Trp-233 during acidification and subsequent desensitization. Together, these observations reveal that ASIC1a opening is accompanied by a distance increase between adjacent thumb and palm domains as well as a movement of Glu-235 relative to the knuckle helix. Our study identifies subunit interactions in the extracellular loop and shows that dynamic changes of these interactions are critical for normal ASIC function.

Les paradoxes de l'argumentation en contexte d'éducation : s'accorder sur les désaccords. Analyse d'interactions argumentatives dans un dispositif de formation en psychologie à l'Université

Dans le chapitre « Les paradoxes de l'argumentation en contexte d'éducation: s'accorder sur les désaccords », Muller Mirza part de l'idée qu'à la différence des situations ordinaires de désaccords, les dispositifs utilisant l'argumentation dans des contextes d'éducation demandent aux participants précisément de résoudre ces désaccords. Leur sont donc interdites, par contrat plus ou moins implicite, les échappatoires auxquelles nous recourons volontiers dans les discours quotidiens qui permettent d'éviter de problématiser la question en discussion. C'est dire qu'elle aborde directement une difficulté souvent signalée dans les études sur l'argumentation en contexte éducatif : la tension entre d'une part l'expression de points de vue différents, étape nécessaire à la construction des connaissances, et d'autre part la préservation de la relation entre les interlocuteurs, de leurs faces. Le chapitre propose comme objet de discussion le rôle de cette tension dans des situations d'apprentissage en analysant des productions argumentatives réalisées dans le cadre d'un dispositif particulier. Il invite ainsi à une réflexion non seulement sur les ingrédients des dispositifs pédagogiques qui permettraient de prendre en compte cette tension mais aussi sur les méthodes d'analyse des interactions argumentatives. L'étude de cas met en scène des étudiants de master en psychologie sociale, dans le cadre d'un jeu de rôle : ils sont placés dans la perspective de leur futur métier, et figurent des psychologues conseillant des éducateurs face à des jeunes qui utilisent des insultes racistes entre eux. Le dispositif mis en oeuvre satisfait quatre exigences d'ordre théorique, favorables selon l'auteure à une bonne résolution des désaccords : le ménagement des faces des interlocuteurs en fixant des rôles ne correspondant pas nécessairement aux positions de chacun ; la construction de connaissances,préalable à la discussion ; la médiation de l'échange par un outil, ici un « chat », qui permet d'échanger les points de vue et d'apporter une dimension réflexive en cours d'interaction sur les points de vue exprimés ; le fait de donner du sens à l'activité, en simulant une situation professionnelle potentielle. L'analyse des échanges a été réalisée sur onze corpus constitués par les étudiants en petits groupes de trois ou quatre travaillant sur un logiciel de « chat ». Les questions abordées étaient les suivantes : Comment les interlocuteurs négocient-ils les désaccords qui apparaissent au cours des échanges? Ces désaccords sont-ils propices à une problématisation? Les participants mettent-ils en oeuvre des dynamiques d'« exploration » du désaccord relevé? Cette analyse, inspirée d'une approche socioculturelle reprise en partie des travaux de Neil Mercer sur les « discours exploratoires », met en évidence des dynamiques argumentatives de qualité au cours desquels les désaccords sont non seulement exprimés mais également problématisés au sein des groupes. Elle met entre autres en évidence que le sens de l'activité pour les étudiants est en partie tributaire d'un contrat didactique et pédagogique : leurs échanges sont la base de leur évaluation universitaire. Néanmoins la similitude entre situation d'enseignement et situation professionnelle a largement été perçue par les étudiants et motivante pour eux, ce qui a certainement concouru également à la qualité des échanges.

Emergent geomorphic-vegetation interactions on a subalpine alluvial fan

Following perturbation, an ecosystem (flora, fauna, soil) should evolve as a function of time at a rate conditioned by external variables (relief, climate, geology). More recently, biogeomorphologists have focused upon the notion of co-development of geomorphic processes with ecosystems over very short through to very long (evolutionary) timescales. Alpine environments have been a particular focus of this co-development. However, work in this field has tended to adopt a simplified view of the relationship between perturbation and succession, including: how the landform and ecosystem itself conditions the impact of a perturbation to create a complex spatial response impact; and how perturbations are not simply ecosystem destroyers but can be a significant source of ecosystem resources. What this means is that at the within landform scale, there may well be a complex and dynamic topographic and sedimentological template that co-develops with soil, flora and fauna. Here, we present and test a conceptual model of this template for a subalpine alluvial fan. We combine detailed floristic inventory with soil inventory, determination of edaphic variables and analysis of historical aerial imagery. Spatial variation in the probability of perturbation of sites on the fan surface was associated with down fan variability in the across-fan distribution of fan ages, fan surface channel characteristics and fan surface sedimentology. Floristic survey confirmed that these edaphic factors distinguished site floristic richness and plant communities up until the point that the soil-vegetation system was sufficiently developed to sustain plant communities regardless of edaphic conditions. Thus, the primary explanatory variable was the estimated age of each site, which could be tied back into perturbation history and its spatial expression due to the geometry of the fan: distinct plant communities were emergent both across fan and down fan, a distribution maintained by the way in which the fan dissipates potentially perturbing events.

Colony-colony interactions between highly invasive ants

Among invasive species, ants are a particularly prominent group with enormous impacts on native biodiversity and ecosystem functioning. Globalization and on-going climate change are likely to increase the rate of ant invasions in the future, leading to simultaneous introductions of several highly invasive species within the same area, Here, we investigate pairwise interactions among four highly invasive species, Linepithema humile,Lashis neglectus, Pheidole megacephala and Wasmannia auropunctata, at the whole colony level, using a laboratory set-up. :Each colony consisted of 300 workers and one queen. The number of surviving workers in the competing colonies was recorded daily over 7 weeks. We modelled the survival of each colony during pairwise colony interactions, using a nonlinear model characterizing the survival dynamics of each colony individually. The least dominant species was P. megacephala, which always went extinct. Interactions among the three other species showed more complex dynamics, rendering the outcome of the interactions less predictable. Overall, W auropunctata and L neglectus were the most dominant species. This study shows the importance of scaling up to the colony level in order to gain realism in predicting the outcome of multiple invasions.

Genomics of clinal variation in Drosophila: disentangling the interactions of selection and demography.

Clines in phenotypes and genotype frequencies across environmental gradients are commonly taken as evidence for spatially varying selection. Classical examples include the latitudinal clines in various species of Drosophila, which often occur in parallel fashion on multiple continents. Today, genomewide analysis of such clinal systems provides a fantastic opportunity for unravelling the genetics of adaptation, yet major challenges remain. A well-known but often neglected problem is that demographic processes can also generate clinality, independent of or coincident with selection. A closely related issue is how to identify true genic targets of clinal selection. In this issue of Molecular Ecology, three studies illustrate these challenges and how they might be met. Bergland et al. report evidence suggesting that the well-known parallel latitudinal clines in North American and Australian D. melanogaster are confounded by admixture from Africa and Europe, highlighting the importance of distinguishing demographic from adaptive clines. In a companion study, Machado et al. provide the first genomic comparison of latitudinal differentiation in D. melanogaster and its sister species D. simulans. While D. simulans is less clinal than D. melanogaster, a significant fraction of clinal genes is shared between both species, suggesting the existence of convergent adaptation to clinaly varying selection pressures. Finally, by drawing on several independent sources of evidence, Bo?ičević et al. identify a functional network of eight clinal genes that are likely involved in cold adaptation. Together, these studies remind us that clinality does not necessarily imply selection and that separating adaptive signal from demographic noise requires great effort and care.

No Evidence for moral reward and punishment in an anonymous context.

Human social interactions are regulated by moral norms that define individual obligations and rights. These norms are enforced by punishment of transgressors and reward of followers. Yet, the generality and strength of this drive to punish or reward is unclear, especially when people are not personally involved in the situation and when the actual impact of their sanction is only indirect, i.e., when it diminishes or promotes the social status of the punished or rewarded individual. In a real-life study, we investigated if people are inclined to anonymously punish or reward a person for her past deeds in a different social context. Participants from three socio-professional categories voted anonymously for early career violinists in an important violin competition. We found that participants did not punish an immoral violin candidate, nor did they reward another hyper-moral candidate. On the contrary, one socio-professional category sanctioned hyper-morality. Hence, salient moral information about past behavior did not elicit punishment or reward in an impersonal situation where the impact of the sanction was indirect. We conclude that contextual features play an important role in human motivation to enforce moral norms.