Analyse de la prégabaline et lacosamide utilisant l’enquête post marketing médicament appareil antiépileptique

The epilepsy community has been the fortunate recipient of a number of new drugs that have come onto the market for the treatment of partial seizures. In addition to being new treatment options, these medications have also expanded the population eligible to receive drug treatment. This expansion of the treatable population to special groups such as the elderly, pregnant women and children has caused doctors to make choices between the available medications based on perceptions of safety. Some key information that could guide a physician’s choice is not typically collected during initial medication trials. We present here a study done to compare the usage and global effectiveness of two medications, Pregabalin and Lacosamide. 158 patients were administered Pregabalin and 137 patients were administered Lacosamide. The average initial frequency of complex partial seizures (CPS) for patients starting Pregabalin was 6 per month and 5.5 per month for patients starting Lacosamide. After six months, CPS frequency decreased to 3.8 and 4 per month for Pregabalin and Lacosamide respectively. However, the patient global assessment did not seem to reflect the comparative effectiveness of the two medications; with assessments of better or much better occurring in 32% of Pregabalin patients and 51% of Lacosamide patients. The global assessments of better or much better were 11% for Pregabalin and 24% for Lacosamide. These results are not what one might expect given the reduction in CPS frequency observed. Also unexpected, given the global assessment distribution, was the 88% retention rate for Lacosamide and the 95% retention rate for Pregabalin respectively. Further study into the relationship between the patient global assessment, CPS frequency, and retention rates might be warranted in further research.Les patients atteints de l’épilepsie ont bénéficié d’un certain nombre de nouveaux médicaments dans le traitement des crises partielles. En plus d’être de nouvelles options de traitement, ces médicaments ont également élargi la population cibles de ces traitements médicamenteux. Cette expansion de la population traitable de groupes particuliers tels que les femmes enceintes, les enfants et les personnes âgées a poussé les médecins à faire des choix entre les médicaments disponibles sur la base de perception de la sécurité. Quelques informations clés qui pourraient guider le choix d’un médecin ne sont généralement pas collectées lors des essais de médicaments initiaux. Nous présentons ici une étude réalisée pour comparer l’utilisation et l’efficacité globale de deux médicaments, la Prégabaline et la Lacosamide. Ils furent administrés chez 158 patients pour la Prégabaline et 137 patients pour Lacosamide. La fréquence initiale moyenne des crises partielles complexes (CPC) pour les patients mis sous Prégabaline était de 6 crises par mois et 5,5 crises par mois pour les patients mis sous Lacosamide. Après six mois, la fréquence des CPC a diminué à 3,8 et à 4 par mois pour Prégabaline et Lacosamide respectivement. Toutefois, l’évaluation globale du patient ne semble pas refléter l’efficacité comparée de ces deux médicaments; avec une évaluation meilleure ou encore plus meilleure de survenue de crises chez 32% des patients mis sous Prégabaline et 51% des patients mis sous Lacosamide. Les évaluations globales d’un meilleur ou encore plus meilleur résultat étaient de 11 % pour la Prégabaline et 24 % pour la Lacosamide. Ces résultats ne sont pas ce que l’on pourrait s’attendre compte tenu de la réduction de la fréquence observée des CPC. Aussi inattendu, compte tenu de la répartition mondiale de l’évaluation, était le taux de rétention de 88% pour Lacosamide et de 95% pour la Prégabaline respectivement. Une étude plus approfondie de la relation entre l’évaluation globale des patients, la fréquence des CPC , et les taux de rétention peut être justifiée dans des recherches ultérieures

Tracing the source of soil organic matter eroded from temperate forest catchments using carbon and nitrogen isotopes

Soil erosion continuously redistributes soil and associated soil organic matter (SOM) on the Earth's surface, with important implications for biogeochemical cycling of essential elements and terrestrial carbon sequestration. Despite the importance of soil erosion, surprisingly few studies have evaluated the sources of eroded carbon (C). We used natural abundance levels of the stable and radioactive isotopes of C (13C and 14C) and stable isotope of nitrogen (15N) to elucidate the origins of SOM eroded from low-order catchments along the western slopes of the Sierra Nevada of California, USA. Our work was conducted in two relatively undisturbed catchments (low elevation = 1800 m, and high elevation = 2300 m) of the Kings River Experimental Watersheds (KREW) in the Sierra National Forest. Sediment captured in basins at the outlet of each gauged watershed were compared to possible source materials, which included: upland surficial organic horizons (i.e., forest floor) and mineral soils (0–0.6 m) from three landform positions (i.e., crest, backslope, and toeslope), stream bank soils (0–0.6 m), and stream-bed materials (0–0.05 m). We found that most of the organic matter (OM) in the captured sediments was composed of O-horizon material that had high C concentrations. Radiocarbon analyses also showed that the captured OM is composed of modern (post-1950) C, with fraction modern values at or above 1.0. Our results suggest that surface (sheet) erosion, as opposed to channeling through established streams and episodic mass wasting events, is likely the largest source of sediment exported out of these minimally disturbed, headwater catchments. The erosional export of sediment with a high concentration of C, especially in the form of relatively undecomposed litter from the O horizon, suggests that a large fraction of the exported C is likely to be decomposed during or after erosion; hence, it is unlikely that soil erosion acts as a significant net sink for atmospheric CO2 in these low-order, temperate forest catchments

Nuclear morphologies: their diversity and functional relevance.

Studies of chromosome and genome biology often focus on condensed chromatin in the form of chromosomes and neglect the non-dividing cells. Even when interphase nuclei are considered, they are often then treated as interchangeable round objects. However, different cell types can have very different nuclear shapes, and these shapes have impacts on cellular function; indeed, many pathologies are linked with alterations to nuclear shape. In this review, we describe some of the nuclear morphologies beyond the spherical and ovoid. Many of the leukocytes of the immune system have lobed nuclei, which aid their flexibility and migration; smooth muscle cells have a spindle shaped nucleus, which must deform during muscle contractions; spermatozoa have highly condensed nuclei which adopt varied shapes, potentially associated with swimming efficiency. Nuclei are not passive passengers within the cell. There are clear effects of nuclear shape on the transcriptional activity of the cell. Recent work has shown that regulation of gene expression can be influenced by nuclear morphology, and that cells can drastically remodel their chromatin during differentiation. The link between the nucleoskeleton and the cytoskeleton at the nuclear envelope provides a mechanism for transmission of mechanical forces into the nucleus, directly affecting chromatin compaction and organisation.Leverhulme Trust (Grant ID: RPG337), Biotechnology and Biological Sciences Research Council (Grant IDs: BB/N000129/1, BB/L502443/1)This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00412-016-0614-

E.P. Thompson and cultural sociology: questions of poetics, capitalism and the commons

There is currently a need for cultural sociology to readdress the work of humanistic and cultural Marxism. While more recently much of this work has been dismissed the appearance of more radical social movements and the on-going crisis of neoliberalism suggests that it still has much to tell us. In this respect, this article seeks to readdress the writing of historian E.P.Thompson arguing that his work on the class based and other social movements, poetics, critique of positivism and economic reason, utopia and work on the idea of the commons all has much to offer more contemporary scholarship. While the article recognises that the cultural Marxism of figures like Thompson can-not simply be resurrected it does continue to offer a number of critical insights lacking from other traditions within cultural sociology. By readdressing the internal complexity of Thompson’s writing the argumentative strategy of this article suggests that cultural sociology needs to move beyond more simplistic understandings of cultural Marxism and more carefully explore what it has to offer

Sensitivity of an Ultrasonic Technique for Axial Stress Determination

In machine assembly it is often required that bolts used to fasten machine parts be installed with specific design preloads. Because it is inconvenient to measure preload directly, preload specifications are usually based on some more easily measured quantity with which the level of preload may be correlated. Most often this quantity is the torque to be applied to the bolt at installation. Studies by Blake and Kurtz [1] and Heyman [2] have shown that when bolts are torqued into place, the fraction of applied torque which translates into useful preload is small and widely variable. This is so because the large majority of applied torque is absorbed in overcoming friction in the bolt’s threads and at the underside of the bolt’s head. Consequently, even though the torque to install different bolts may be identical, small variations in frictional conditions from one installation to the next can result in large variations in preload. The unreliability of torque as an indicator of preload has been the motivating factor behind the development of a number of alternate methods of measurement [2–5]

The removal of thermally aged films of triacylglycerides by surfactant solutions

Thermal ageing of triacylglycerides (TAG) at high temperatures produces films which resist removal using aqueous surfactant solutions. We used a mass loss method to investigate the removal of thermally aged TAG films from hard surfaces using aqueous solutions of surfactants of different charge types. It was found that cationic surfactants are most effective at high pH, whereas anionics are most effective at low pH and a non-ionic surfactant is most effective at intermediate pH. We showed that the TAG film removal process occurs in several stages. In the first ‘‘lag phase’’ no TAG removal occurs; the surfactant first partitions into the thermally aged film. In the second stage, the TAG film containing surfactant was removed by solubilisation into micelles in the aqueous solution. The effects of pH and surfactant charge on the TAG removal process correlate with the effects of these variables on the extent of surfactant partitioning to the TAG film and on the maximum extent of TAG solubilisation within the micelles. Additionally, we showed how the TAG removal is enhanced by the addition of amphiphilic additives such as alcohols which act as co-surfactants. The study demonstrates that aqueous surfactant solutions provide a viable and more benign alternative to current methods for the removal of thermally aged TAG films

Correlations between atazanavir Ctrough and hyperbilirubinemia: a case report

<p>Abstract</p> <p>Introduction</p> <p>Hyperbilirubinemia is a common side effect of the antiretroviral agent atazanavir but is generally reversible upon discontinuation of treatment. We used therapeutic drug monitoring to investigate the occurrence of hyperbilirubinemia in a 49-year-old Hispanic man infected with HIV, following an overdose of ritonavir in ritonavir-boosted atazanavir therapy.</p> <p>Case presentation</p> <p>A 49-year-old Hispanic man with HIV who had received several highly active antiretroviral therapy regimens over a number of years including atazanavir-containing regimens, was diagnosed with hyperbilirubinemia. An inappropriate doubling of ritonavir boosting resulted in a high atazanavir C_troughand an initial rise in bilirubin plasma levels. Bilirubin levels later decreased, probably as a consequence of enzyme induction, while atazanavir plasma concentrations remained elevated.</p> <p>Conclusion</p> <p>This article describes an occurrence of hyperbilirubinemia in a man infected with HIV and supports the importance of therapeutic drug monitoring in investigations of hyperbilirubinemia among patients receiving antiretroviral agents. That the patient tolerated exceptionally high atazanavir levels further strengthens the tolerability profile of this drug.</p

Self-Organization, Layered Structure, and Aggregation Enhance Persistence of a Synthetic Biofilm Consortium

Microbial consortia constitute a majority of the earth’s biomass, but little is known about how these cooperating communities persist despite competition among community members. Theory suggests that non-random spatial structures contribute to the persistence of mixed communities; when particular structures form, they may provide associated community members with a growth advantage over unassociated members. If true, this has implications for the rise and persistence of multi-cellular organisms. However, this theory is difficult to study because we rarely observe initial instances of non-random physical structure in natural populations. Using two engineered strains of Escherichia coli that constitute a synthetic symbiotic microbial consortium, we fortuitously observed such spatial self-organization. This consortium forms a biofilm and, after several days, adopts a defined layered structure that is associated with two unexpected, measurable growth advantages. First, the consortium cannot successfully colonize a new, downstream environment until it selforganizes in the initial environment; in other words, the structure enhances the ability of the consortium to survive environmental disruptions. Second, when the layered structure forms in downstream environments the consortium accumulates significantly more biomass than it did in the initial environment; in other words, the structure enhances the global productivity of the consortium. We also observed that the layered structure only assembles in downstream environments that are colonized by aggregates from a previous, structured community. These results demonstrate roles for self-organization and aggregation in persistence of multi-cellular communities, and also illustrate a role for the techniques of synthetic biology in elucidating fundamental biological principles

Temporal Model Adaptation for Person Re-Identification

Person re-identification is an open and challenging problem in computer vision. Majority of the efforts have been spent either to design the best feature representation or to learn the optimal matching metric. Most approaches have neglected the problem of adapting the selected features or the learned model over time. To address such a problem, we propose a temporal model adaptation scheme with human in the loop. We first introduce a similarity-dissimilarity learning method which can be trained in an incremental fashion by means of a stochastic alternating directions methods of multipliers optimization procedure. Then, to achieve temporal adaptation with limited human effort, we exploit a graph-based approach to present the user only the most informative probe-gallery matches that should be used to update the model. Results on three datasets have shown that our approach performs on par or even better than state-of-the-art approaches while reducing the manual pairwise labeling effort by about 80%