Multi-layer amniotic membrane (MLAM) transplantation for non traumatic corneal perforations or descemetoceles

Purpose:To describe the indications, the surgical procedure and the clinical outcome of MLAM in the treatment of non traumatic corneal perforations and descemetoceles . Methods:A prospective, non comparative, interventional case series of eight consecutive patients (mean age 59 years old, 6 men and 2 women) with non traumatic corneal perforations or descemetoceles.The surgery consisted in a MLAM transplantation of a cryopreservated human amniotic membrane. The series included: three active herpetic keratitis, one rosacea, one perforation of an hydrops, one cicatricial pemphigoid, one perforation after an abcess in a corneal graft and one perforation after protonbeamtherapy. The clinical outcome included: the follow-up, the integrity of the eye, corneal epithelialization, inflammation and neovascularization, and the integration of the MLAM. Stromal thickness was followed precisely with the slit lamp. A corneal graft was performed at one patient after the MLAM, allowing microscopic investigation of the removed MLAM integrated in the cornea. Results:The mean follow-up was 8.78 months (range 3.57 to 30.17). Amniotic membrane transplantation was successful and reduced inflammation in 7 patients out of 8 ,after one procedure.One patient who presented a large herpetic keratitis epithelial defect with corneal anaesthesia had his MLAM dissolved after two weeks with an aqueous leakage. Epithelium healed within 3 weeks above 7 MLAM and remained stable at 3 months in 7 out of 8 patients. MLAM opacification gradually disappeared over a few months, however, stromal layers filling in the corneal perforations or above the descemetoceles remained stable. Conclusions:MLAM transplantation is a safe, effective and useful technique to cure non traumatic corneal perforations and descemetoceles. It can be performed in emergency despite the presence of an active inflammation or infection. By facilitating epithelialization, reducing inflammation and neovascularization, it allows corneal surface reconstruction in patients with persistent epithelial defects and corneal melting that usually ends in a perforation. For full visual rehabilitation, a delayed penetrating keratoplasty is required.

Multi-faceted functions of secretory IgA at mucosal surfaces.

Secretory IgA (SIgA) plays an important role in the protection and homeostatic regulation of intestinal, respiratory, and urogenital mucosal epithelia separating the outside environment from the inside of the body. This primary function of SIgA is referred to as immune exclusion, a process that limits the access of numerous microorganisms and mucosal antigens to these thin and vulnerable mucosal barriers. SIgA has been shown to be involved in avoiding opportunistic pathogens to enter and disseminate in the systemic compartment, as well as tightly controlling the necessary symbiotic relationship existing between commensals and the host. Clearance by peristalsis appears thus as one of the numerous mechanisms whereby SIgA fulfills its function at mucosal surfaces. Sampling of antigen-SIgA complexes by microfold (M) cells, intimate contact occurring with Peyer's patch dendritic cells (DC), down-regulation of inflammatory processes, modulation of epithelial, and DC responsiveness are some of the recently identified processes to which the contribution of SIgA has been underscored. This review aims at presenting, with emphasis at the biochemical level, how the molecular complexity of SIgA can serve these multiple and non-redundant modes of action.

A Novel Autonomous Observation Platform for Multi-Disciplinary Investigations at the Cape Verde Ocean Observatory (CVOO)

In order to investigate the spatial and temporal variability (daily, seasonal and inter-annual) of CO2 and O2 air-sea fluxes and their underlying processes, a dense network of observations is required. For this purpose, the Cape Verde Ocean Observatory (CVOO) provides a unique infrastructure. Information thus obtained also links biological productivity and atmospheric composition. To expand these capabilities, a novel “virtual mooring” approach for high resolution measurements, based on a modified NEMO profiling float, is pursued. This Profiling Float was equipped with O2 and pCO2 sensors for the first time, in order to collect daily depth profiles (0-200 m) in the vicinity of the ocean site. Data access and remote control is provided through Iridium satellite telemetry. Recalibrations and redeployments are carried out every 1-3 month. First, we present the new developed instrument and the innovative in situ and real-time approach behind. Second, we show the inter-disciplinary scientific objectives which will benefit from this approach as a result of the intensive partnership between IFM-GEOMAR and INDP during the last years.

Controlled nerve growth factor release from multi-ply alginate/chitosan-based nerve conduits.

The delivery kinetics of growth factors has been suggested to play an important role in the regeneration of peripheral nerves following axotomy. In this context, we designed a nerve conduit (NC) with adjustable release kinetics of nerve growth factor (NGF). A multi-ply system was designed where NC consisting of a polyelectrolyte alginate/chitosan complex was coated with layers of poly(lactide-co-glycolide) (PLGA) to control the release of embedded NGF. Prior to assessing the in vitro NGF release from NC, various release test media, with and without stabilizers for NGF, were evaluated to ensure adequate quantification of NGF by ELISA. Citrate (pH 5.0) and acetate (pH 5.5) buffered saline solutions containing 0.05% Tween 20 yielded the most reliable results for ELISA active NGF. The in vitro release experiments revealed that the best results in terms of reproducibility and release control were achieved when the NGF was embedded between two PLGA layers and the ends of the NC tightly sealed by the PLGA coatings. The release kinetics could be efficiently adjusted by accommodating NGF at different radial locations within the NC. A sustained release of bioactive NGF in the low nanogram per day range was obtained for at least 15days. In conclusion, the developed multi-ply NGF loaded NC is considered a suitable candidate for future implantation studies to gain insight into the relationship between local growth factor availability and nerve regeneration.

Les activités de la francophonie réalisées dans certaines écoles secondaires de Santiago et São Vicente– CapVert: leurs impactes sur l'apprentissage du français

Pour mieux diffuser la langue française au monde, une date a été choisie, 20 mars. Des manifestations, dans le monde entier, célèbrent le rayonnement de la langue française. C’est un événement riche en activités divers qui mobilise chaque année de nombreux institutions, missions diplomatiques et culturelles, associations et individus. Nous avons remarqué que la journée de la francophonie, c’est une date qui est célébrée aussi par les CapVerdiens, spécialement par les lycéens. Dans les différents lycées CapVerdiens, notamment Santiago et São Vicente, nous constatons que cette date c’est l’occasion pour les apprenants d’exprimer leur goût prononcé pour la scène. Que ce soit en sketchs ou en chansons, en déclamations poétiques ou en histoires drôles, les apprenants démontrent une fois, leur plaisir à jouer, chanter, et rire en langue française. C’est dans cette optique, que s’intègre ce mémoire dont l’objet est de vérifier ou non si ces activités ont un impact positif dans l’apprentissage de la langue française. Nous avons donc, proposé de traiter le thème : Les activités de la francophonie réalisées dans certaines écoles secondaires de Santiago et São Vicente– CapVert : leurs impactes sur l'apprentissage du français. Nous aborderons dans un premier temps, de façon théorique, l’histoire de la francophonie en nous référant à de nombreuses sources d’informations et ouvrages différents traitant du sujet. La francophonie est complexe, elle a des notions de communauté de pays, de peuple, de langue parlées, et de valeurs, c’est dans ce cadre que nous nous intéresserons dans la même partie à comprendre se qu'est la francophonie, ces différentes définitions et sens à elle accordé. Nous développerons, ensuite, le parcours de la langue française au CapVert, où nous analyserons sa présence et son introduction dans l'enseignement secondaire. De même, nous analyserons l'histoire de la francophonie dans cet archipel, où nous présenterons les raisons de l'adhésion du CapVert à l'Organisation International de la Francophonie, et les intérêts du CapVert comme membre de cette organisation. Nous observerons l’influence que le théâtre, le chant, la comédie musical, le sketch entre autres activités, ont sur le déroulement des cours que sur les activités extra scolaire. C’est dans cette optique que dans la troisième partie, nous ferons une étude de cas des activités de la francophonie réalisées par les apprenants dans les écoles secondaires de Santiago et São Vicente. Nous tenterons d’établir ainsi l’influence des différentes activités et l’adhésion des élèves et professeurs. Cette étude s’appuiera sur des questionnaires remis aux enseignants et apprenants. Finalement, nous proposerons des perspectives et des suggestions pour l’exploitation de ces activités en classe de langue. Dans cette partie, nous proposerons des stratégies qui permettront aux enseignants de développer une véritable dynamique dans leurs actions en consacrant davantage de leur temps aux animations en français dans les lycées.

A Multi-Center Phase II Study (SAKK 36/06) of Single Agent Everolimus (RAD001) In Patients with Relapsed or Refractory Mantle Cell Lymphoma

Introduction: Mantle cell lymphoma (MCL) accounts for 6% of all B-cell lymphomas and remains incurable for most patients. Those who relapse after first line therapy or hematopoietic stem cell transplantation have a dismal prognosis with short response duration after salvage therapy. On a molecular level, MCL is characterised by the translocation t[11;14] leading to Cyclin D1 overexpression. Cyclin D1 is downstream of the mammalian target of rapamycin (mTOR) kinase and can be effectively blocked by mTOR inhibitors such as temsirolimus. We set out to define the single agent activity of the orally available mTOR inhibitor everolimus (RAD001) in a prospective, multi-centre trial in patients with relapsed or refractory MCL (NCT00516412). The study was performed in collaboration with the EU-MCL network. Methods: Eligible patients with histologically/cytologically confirmed relapsed (not more than 3 prior lines of systemic treatment) or refractory MCL received everolimus 10 mg orally daily on day 1 - 28 of each cycle (4 weeks) for 6 cycles or until disease progression. The primary endpoint was the best objective response with adverse reactions, time to progression (TTP), time to treatment failure, response duration and molecular response as secondary endpoints. A response rate of ≤ 10% was considered uninteresting and, conversely, promising if ≥ 30%. The required sample size was 35 pts using the Simon's optimal two-stage design with 90% power and 5% significance. Results: A total of 36 patients with 35 evaluable patients from 19 centers were enrolled between August 2007 and January 2010. The median age was 69.4 years (range 40.1 to 84.9 years), with 22 males and 13 females. Thirty patients presented with relapsed and 5 with refractory MCL with a median of two prior therapies. Treatment was generally well tolerated with anemia (11%), thrombocytopenia (11%), neutropenia (8%), diarrhea (3%) and fatigue (3%) being the most frequent complications of CTC grade III or higher. Eighteen patients received 6 or more cycles of everolimus treatment. The objective response rate was 20% (95% CI: 8-37%) with 2 CR, 5 PR, 17 SD, and 11 PD. At a median follow-up of 6 months, TTP was 5.45 months (95% CI: 2.8-8.2 months) for the entire population and 10.6 months for the 18 patients receiving 6 or more cycles of treatment. Conclusion: This study demonstrates that single agent everolimus 10 mg once daily orally is well tolerated. The null hypothesis of inactivity could be rejected indicating a moderate anti-lymphoma activity in relapsed/refractory MCL. Further studies of either everolimus in combination with chemotherapy or as single agent for maintenance treatment are warranted in MCL.

Proverbes, dictons et expressions imagées dans l’enseignement/apprentissage du FLE, dans le secondaire au Cap-Vert.

Pour bien maîtriser une langue, il faut sans doute en avoir une connaissance la plus large possible, ce qui demande alors l’enseignement/apprentissage de tous les éléments qui la composent. Dans ce cas, il est très important de savoir quels sont, parmi ces éléments, ceux qui sont amenés en classe et comment ils y sont présentés. Il y en a certains qui ne fi-gurent pas dans le programme destiné à l’enseignement/apprentissage de la langue fran-çaise. S’ils l’étaient, probablement ils seraient enseignés. Mais, d’après notre constat, non seulement ils ne figurent pas, comme ils ne sont pas ou presque pas traités en cours par l’initiative des professeurs, bien qu’ils soient parmi les éléments les plus importants dans l’apprentissage d’une langue. Très souvent, ce sont ces éléments qui sont à la base de la motivation pour l’apprentissage des langues puisqu’ils constituent, d’une certaine manière, le charme et la beauté d’une langue. Nous en avons pris trois (proverbe, dicton et expres-sion imagée), qui peuvent représenter la manière de vivre ; de penser ; la culture, les cou-tumes et les habitudes d’un peuple. Il faut préciser que ce constat nous l’avons fait depuis longtemps. Par conséquent, nous avons décidé de traduire l’inquiétude que cette problématique provoque chez nous en ce travail de recherche qui a été mené sous le thème de : Proverbes, dictons et expres-sions imagées dans l’enseignement/apprentissage du FLE, dans le secondaire au Cap- Vert. Dans l’ensemble, ce travail est composé de trois parties. Dans la première partie, après les consultations de documents, nous avons proposé une réflexion sur le proverbe, le dicton et l’expression imagée en ce qui concerne leur origine et leur contexte social, temporel, leur durée, et leur situation actuelle par rapport à leur utilisation ou leur étude. Nous en avons également présenté quelques définitions, en insistant sur la distinction entre les mêmes, vu que pendant les recherches, nous avons constaté qu’il y a parfois, une confusion entre eux. Puis, dans la deuxième partie, à travers des enquêtes qui ont été menées sur le terrain dans quelques lycées de Praia, nous avons présenté sous forme d’analyse, la situation ac-tuelle concernant le recours aux proverbes, dictons et expressions imagées par le professeur dans ses cours, bien comme l’intérêt et la motivation des élèves face aux mêmes. Finalement, dans la troisième et dernière partie, nous avons dressé une liste composée de proverbes, dictons et expressions imagées que nous avons fait accompagner de leur pays d’origine, quand cela a été possible. Ils ont été analysés et nous avons essayé de montrer également, l’utilité pratique de leur message, soit pour les élèves à l’école, soit d’une ma-nière plus générale, pour toute la vie dans la société. Pour donner un caractère pratique à notre travail, nous avons fait quelques proposi-tions de techniques d’exploitation de proverbes, dictons et expressions imagées, dans les classes. C’est-à-dire, nous avons essayé d’apporter des suggestions qui peuvent être appli-quées à un éventuel engagement de la part des professeurs ou d’autres intervenants concer-nés à la résolution de la problématique qui a légitimé notre recherche.

A multi-objective model for a multi-period distribution management problem

The problems arising in commercial distribution are complex and involve several players and decision levels. One important decision is relatedwith the design of the routes to distribute the products, in an efficient and inexpensive way.This article deals with a complex vehicle routing problem that can beseen as a new extension of the basic vehicle routing problem. The proposed model is a multi-objective combinatorial optimization problemthat considers three objectives and multiple periods, which models in a closer way the real distribution problems. The first objective is costminimization, the second is balancing work levels and the third is amarketing objective. An application of the model on a small example, with5 clients and 3 days, is presented. The results of the model show the complexity of solving multi-objective combinatorial optimization problems and the contradiction between the several distribution management objective.

Need of reduced and harmonized bureaucracy in multi-centre clinical research - a case-report from a Swiss trial

Introduction: We launched an investigator-initiated study (ISRCTN31181395) to evaluate the potential benefit of pharmacokinetic-guided dosage individualization of imatinib for leukaemiapatients followed in public and private sectors. Following approval by the research ethics committee (REC) of the coordinating centre, recruitment throughout Switzerland necessitatedto submit the protocol to 11 cantonal RECs.Materials and Methods: We analysed requirements and evaluation procedures of the 12 RECs with associated costs.Results: 1-18 copies of the dossier, in total 4300 printed pages, were required (printing/posting costs: ~300 CHF) to meet initial requirements. Meeting frequencies of RECs ranged between 2 weeks and 2 months, time from submission to fi rst feedback took 2-75 days. Study approval was obtained from a chairman, a subor the full committee, the evaluation work being invoiced by0-1000 CHF (median: 750 CHF, total: 9200 CHF). While 5 RECs gave immediate approval, the other 6 rose in total 38 queries before study release, mainly related to wording in the patient information, leading to 7 different fi nal versions approved. Submission tasks employed an investigator half-time over about 6 months.Conclusion: While the necessity of clinical research evaluation by independent RECs is undisputed, there is a need of further harmonization and cooperation in evaluation procedures. Current administrative burden is indeed complex, time-consuming and costly. A harmonized electronic application form, preferably compatible with other regulatory bodies and European countries, could increase transparency, improve communication, and encourage academic multi-centre clinical research in Switzerland.

Multi-scale integration and predictability in resting state brain activity.

The human brain displays heterogeneous organization in both structure and function. Here we develop a method to characterize brain regions and networks in terms of information-theoretic measures. We look at how these measures scale when larger spatial regions as well as larger connectome sub-networks are considered. This framework is applied to human brain fMRI recordings of resting-state activity and DSI-inferred structural connectivity. We find that strong functional coupling across large spatial distances distinguishes functional hubs from unimodal low-level areas, and that this long-range functional coupling correlates with structural long-range efficiency on the connectome. We also find a set of connectome regions that are both internally integrated and coupled to the rest of the brain, and which resemble previously reported resting-state networks. Finally, we argue that information-theoretic measures are useful for characterizing the functional organization of the brain at multiple scales.