Bortezomib(Velcade®)-Thalidomide-Dexamethasone (VTD) Is Superior to Thalidomide-Dexamethasone (TD) In Patients with Multiple Myeloma (MM) Progressing or Relapsing After Autologous Transplantation

Introduction: The Thalidomide-Dexamethasone (TD) regimen has provided encouraging results in relapsed MM. To improve results, bortezomib (Velcade) has been added to the combination in previous phase II studies, the so called VTD regimen. In January 2006, the European Group for Blood and Marrow Transplantation (EBMT) and the Intergroupe Francophone du Myélome (IFM) initiated a prospective, randomized, parallel-group, open-label phase III, multicenter study, comparing VTD (arm A) with TD (arm B) for MM patients progressing or relapsing after autologous transplantation. Patients and Methods: Inclusion criteria: patients in first progression or relapse after at least one autologous transplantation, including those who had received bortezomib or thalidomide before transplant. Exclusion criteria: subjects with neuropathy above grade 1 or non secretory MM. Primary study end point was time to progression (TTP). Secondary end points included safety, response rate, progression-free survival (PFS) and overall survival (OS). Treatment was scheduled as follows: bortezomib 1.3 mg/m2 was given as an i.v bolus on Days 1, 4, 8 and 11 followed by a 10-Day rest period (days 12 to 21) for 8 cycles (6 months) and then on Days 1, 8, 15, 22 followed by a 20-Day rest period (days 23 to 42) for 4 cycles (6 months). In both arms, thalidomide was scheduled at 200 mg/Day orally for one year and dexamethasone 40 mg/Day orally four days every three weeks for one year. Patients reaching remission could proceed to a new stem cell harvest. However, transplantation, either autologous or allogeneic, could only be performed in patients who completed the planned one year treatment period. Response was assessed by EBMT criteria, with additional category of near complete remission (nCR). Adverse events were graded by the NCI-CTCAE, Version 3.0.The trial was based on a group sequential design, with 4 planned interim analyses and one final analysis that allowed stopping for efficacy as well as futility. The overall alpha and power were set equal to 0.025 and 0.90 respectively. The test for decision making was based on the comparison in terms of the ratio of the cause-specific hazards of relapse/progression, estimated in a Cox model stratified on the number of previous autologous transplantations. Relapse/progression cumulative incidence was estimated using the proper nonparametric estimator, the comparison was done by the Gray test. PFS and OS probabilities were estimated by the Kaplan-Meier curves, the comparison was performed by the Log-Rank test. An interim safety analysis was performed when the first hundred patients had been included. The safety committee recommended to continue the trial. Results: As of 1st July 2010, 269 patients had been enrolled in the study, 139 in France (IFM 2005-04 study), 21 in Italy, 38 in Germany, 19 in Switzerland (a SAKK study), 23 in Belgium, 8 in Austria, 8 in the Czech republic, 11 in Hungary, 1 in the UK and 1 in Israel. One hundred and sixty nine patients were males and 100 females; the median age was 61 yrs (range 29-76). One hundred and thirty six patients were randomized to receive VTD and 133 to receive TD. The current analysis is based on 246 patients (124 in arm A, 122 in arm B) included in the second interim analysis, carried out when 134 events were observed. Following this analysis, the trial was stopped because of significant superiority of VTD over TD. The remaining patients were too premature to contribute to the analysis. The number of previous autologous transplants was one in 63 vs 60 and two or more in 61 vs 62 patients in arm A vs B respectively. The median follow-up was 25 months. The median TTP was 20 months vs 15 months respectively in arm A and B, with cumulative incidence of relapse/progression at 2 years equal to 52% (95% CI: 42%-64%) vs 70% (95% CI: 61%-81%) (p=0.0004, Gray test). The same superiority of arm A was also observed when stratifying on the number of previous autologous transplantations. At 2 years, PFS was 39% (95% CI: 30%-51%) vs 23% (95% CI: 16%-34%) (A vs B, p=0.0006, Log-Rank test). OS in the first two years was comparable in the two groups. Conclusion: VTD resulted in significantly longer TTP and PFS in patients relapsing after ASCT. Analysis of response and safety data are on going and results will be presented at the meeting.

Expectation to improve cardiovascular risk factors control in participants to a health promotion program.

BACKGROUND: We assessed expectations to improve cardiovascular disease risk factors (CVD-RF) in participants to a health promotion program. PARTICIPANTS AND METHODS: Blood pressure (BP), blood glucose (BG), blood total cholesterol (TC), body mass index (BMI), and self-reported smoking were assessed in 1,598 volunteers from the general public (men: 40%; mean age: 56.7 +/- 12.7 years) participating in a mobile health promotion program in the Vaud canton, Switzerland. Participants were asked about their expectation to have their CVD-RF improved at a next visit scheduled 2-3 years later. RESULTS: Expectation for improved control was found in 90% of participants with elevated BP, 91% with elevated BG, 45% with elevated TC, 44% who were overweight, and 35% who were smoking. Expectation for TC improvement was reported more often by men, persons with high level of TC, and persons who had consulted a doctor in the past 12 months. Expectations to lose weight and to quit smoking were found more often in younger persons than the older ones. CONCLUSION: Volunteers from the general population participating in a health promotion program expected improved control more often for hypertension and dysglycemia than for dyslipidemia, overweight and smoking.

Social evolution: war of the worms.

The discovery of a non-reproductive soldier caste in a clonally reproducing trematode greatly extends the taxonomic distribution of eusociality and reaffirms the importance of relatedness in the evolution of reproductive altruism.

Missed appointments in an outpatient clinic for adolescents, an approach to predict the risk of missing.

PURPOSE: To predict the risk of an adolescent patient to miss an appointment, based on the previous appointments and on the characteristics of the patient and the appointment. METHODS: Two thousand one hundred ninety-three (1873 females) patients aged 12 to 20 years having scheduled at least four appointments were included. We assessed the rate of missed nonexcused appointments of each patient. Second, a Markovian multilevel model was used to predict the risk of defaulting. RESULTS: Forty-five percent of the patients have not missed even once, and 14% of females and 17% of males have missed >25% of their appointments. Females show two types of behaviors (an abstract concept that groups individuals based on a combination of their appointment-keeping and their recorded type of healthcare need) depending on the diagnosis. Somatic, gynecology, violence, and counseling diagnoses are mostly grouped together. In this group, having already missed and having an appointment with a paramedical provider increases the risk of missing. In the second group (eating disorders and psychiatric diagnoses) having already missed and a longer delay between appointments influence the risk of missing, although the risk is lower for this latter group. Males only show one type of behavior regarding missed appointments. Having missed a previous appointment, being older, having cancelled the next to last appointment and the type of diagnosis explain the risk of missing. CONCLUSIONS: Patients who have already defaulted have a higher risk of defaulting again. Means of control regarding missed appointments should consequently focus on defaulters, to decrease the associated workload. Reminders could be a solution for the follow-up appointments scheduled with a long delay.

Appropriate maintenance treatment for Crohn's disease: results of a multidisciplinary international expert panel - EPACT II

Introduction: Biological. therapy has dramatically changed management of Crohn's disease (CD). New data have confirmed the benefit and relative long-term safety of anti-TNF alpha inhibition as part of a regular scheduled administration programme. The EPACT appropriateness criteria for maintenance treatment after medically-induced remission (MIR) or surgically-induced remission (SIR) of CD thus required updating. Methods: A multidisciplinary international expert panel (EPACT II, Geneva, Switzerland) discussed and anonymously rated detailed, explicit clinical indications based on evidence in the literature and personal expertise. Median ratings (on a 9-point scale) were stratified into three assessment categories: appropriate (7-9), uncertain (4-6 and/or disagreement) and inappropriate (1-3). Experts ranked appropriate medication according to their own clinical practice, without any consideration of cost. Results: Three hundred and ninety-two specific indications for maintenance treatment of CD were rated (200 for MIR and 192 for SIR). Azathioprine, methotrexate and/or anti-TNF alpha antibodies were considered appropriate in 42 indications, corresponding to 68% of all appropriate interventions (97% of MIR and 39% of SIR). The remaining appropriate interventions consisted of mesalazine and a "wait-and-see" strategy. Factors that influenced the panel's voting were patient characteristics and outcome of previous treatment. Results favour use of anti-TNF alpha agents after failure of any immunosuppressive therapy, while earlier primary use remains controversial. Conclusion: Detailed explicit appropriateness criteria (EPACT) have been updated for maintenance treatment of CD. New expert recommendations for use of the classic immunosuppressors as well as anti-TNF alpha agents are now freely available online (www.epact.ch). The validity of these criteria should now be tested by prospective evaluation. (C) 2009 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

SWIVIT - Swiss video-intubation trial evaluating video-laryngoscopes in a simulated difficult airway scenario: study protocol for a multicenter prospective randomized controlled trial in Switzerland.

BACKGROUND: Video-laryngoscopes are marketed for intubation in difficult airway management. They provide a better view of the larynx and may facilitate tracheal intubation, but there is no adequately powered study comparing different types of video-laryngoscopes in a difficult airway scenario or in a simulated difficult airway situation. METHODS/DESIGN: The objective of this trial is to evaluate and to compare the clinical performance of three video-laryngoscopes with a guiding channel for intubation (Airtraq?, A. P. Advance?, King Vision?) and three video-laryngoscopes without an integrated tracheal tube guidance (C-MAC?, GlideScope?, McGrath?) in a simulated difficult airway situation in surgical patients. The working hypothesis is that each video-laryngoscope provides at least a 90% first intubation success rate (lower limit of the 95% confidence interval >0.9). It is a prospective, patient-blinded, multicenter, randomized controlled trial in 720 patients who are scheduled for elective surgery under general anesthesia, requiring tracheal intubation at one of the three participating hospitals. A difficult airway will be created using an extrication collar and taping the patients' head on the operating table to substantially reduce mouth opening and to minimize neck movement. Tracheal intubation will be performed with the help of one of the six devices according to randomization. Insertion success, time necessary for intubation, Cormack-Lehane grade and percentage of glottic opening (POGO) score at laryngoscopy, optimization maneuvers required to aid tracheal intubation, adverse events and technical problems will be recorded. Primary outcome is intubation success at first attempt. DISCUSSION: We will simulate the difficult airway and evaluate different video-laryngoscopes in this highly realistic and clinically challenging scenario, independently from manufacturers of the devices. Because of the sufficiently powered multicenter design this study will deliver important and cutting-edge results that will help clinicians decide which device to use for intubation of the expected and unexpected difficult airway. TRIAL REGISTRATION: NCT01692535.

Preoperative hyperfractionated accelerated radiotherapy (HART) and concomitant CPT-11 in locally advanced rectal carcinoma: a phase I study.

PURPOSE: Patients with locally advanced rectal carcinoma are at risk for both local recurrence and distant metastases. We demonstrated the efficacy of preoperative hyperfractionated accelerated radiotherapy (HART). In this Phase I trial, we aimed at introducing chemotherapy early in the treatment course with both intrinsic antitumor activity and a radiosensitizer effect. METHODS AND MATERIALS: Twenty-eight patients (19 males; median age 63, range 28-75) with advanced rectal carcinoma (cT3: 24; cT4: 4; cN+: 12; M1: 5) were enrolled, including 8 patients treated at the maximally tolerated dose. Escalating doses of CPT-11 (30-105 mg/m(2)/week) were given on Days 1, 8, and 15, and concomitant HART (41.6 Gy, 1.6 Gy bid x 13 days) started on Day 8. Surgery was to be performed within 1 week after the end of radiochemotherapy. RESULTS: Twenty-six patients completed all preoperative radiochemotherapy as scheduled; all patients underwent surgery. Dose-limiting toxicity was diarrhea Grade 3 occurring at dose level 6 (105 mg/m(2)). Hematotoxicity was mild, with only 1 patient experiencing Grade 3 neutropenia. Postoperative complications (30 days) occurred in 7 patients, with an anastomotic leak rate of 22%. CONCLUSIONS: The recommended Phase II dose of CPT-11 in this setting is 90 mg/m(2)/week. Further Phase II exploration at this dose is warranted.

L'équité d'accès aux ressources en eau : fin ou moyen d'amélioration de l'efficacité de l'irrigation ? : la gestion des ressources en eau dans l'état du Gujarat (Inde) dans la perpective de la political ecology

La thèse présentée ici est le résultat d'une étroite collaboration avec une ONG indienne, AKRSP(I), intervenant dans le développement de l'irrigation au Gujarat depuis plus de 25 ans. Un SIG prototype a été mis en oeuvre et nous permet de proposer ime analyse spatiale et quantitative de l'action de cette ONG ainsi qu'une réflexion plus générale sur les leviers de mise en valeur et de gestion des ressources en eau à des fins agricoles. On peut souligner trois principaux enseignements: Les perspectives d'application des SIG au sein des ONG sont manifestes. Les exigences des bailleurs de fonds peuvent néanmoins faire obstacle à leur développement car, indi-rectement, ils favorisent la mise en oeuvre de SI voués à la justification plutôt qu'à la planification et au suivi des programmes d'actions. Ce résultat soulève la question de la pertinence de l'encadrement, des critères d'évaluation et de la conditionnalité de l'aide publique au développement. Les ONG ont un fort potentiel pour participer à la mise en valeur des ressources en eau en Inde et aider à relever le défi agro-démographique indien, en particulier dans les zones marginales où les services étatiques sont en retrait. Les stratégies d'action basées principalement sur l'application des instruments économiques et techniques doivent cependant être modifiées. Nous montrons qu'elles favorisent une inégalité d'accès aux ressources qui débouche sur une efficacité limitée des pratiques d'irrigation, sur un plan agro-technique. Ces résultats soulignent la nécessité de poursuivre une réflexion critique des discours et solutions dominants en matière de gestion des ressources en eau. Deux pistes d'amélioration sont avancées: 1. considérer l'équité d'accès comme un moyen d'optimiser la gestion de la ressource (limiter le volume d'eau par agriculteur pour encourager les choix de cultures irriguées peu consommatrices et l'adoption des technologies d'économie d'eau), 2. prêter attention à l'ordre dans lequel les différents instruments de gestion disponibles sont employés afin de les articuler dans un séquençage temporel pertinent. La Political Ecology apparait comme un cadre conceptuel très pertinent pour engager cette réflexion critique. Elle permet d'intégrer différentes échelles d'asymétries de pouvoirs à la compréhension des situations et des blocages observables localement : inégalités de capabilités et forces socio-politiques à l'échelle locale, politiques agro-industrielles (coton) et jeux d'alliances politiques des castes à l'échelle nationale, discours et conflits idéologiques ou orientations stratégiques des bailleurs de fonds à l'échelle internationale... Notre recherche empirique contribue modestement au développement de cette Political Ecology de la mise en valeur et de la gestion des ressources en eau. - The present research is based on a close collaboration with an indian NGO, AKRSP(I), which is active in the development of irrigation facilities in Gujarat for the past 25 years. We built a GIS prototype providing quantitative and spatial datas to analyse the NGO intervention and propose a general reflection about water resources development and management issues. Three main findings may be emphasized : The potential of GIS within the workings of an NGO is obvious, as an information ma-nagement tool as much as for developing analytical capacity. However, financial backers expectations may not favour a relevant development of this technology. Indirectly, they promote Information Systems built to justify rather than to plan or monitor action pro¬grammes. This raises the question of stricter framework, conditionality criters and stan¬dardised assessment indicators surrounding official development assistance. There is strong potential that NGOs can assist with the improvement of water resources in India. They can help in overcoming Indian demographic-related agricultural challenges, especially in marginal rural areas neglected by state services. However, intervention strategies mainly based on technical and economic management tools has to be adapted. We found that they lead to inequitable access and distribution of water resources what induces a low efficiency of irrigation practices from an agro-technical point of view. These results underline the need to go further in criticizing dominant ideas and guidelines regarding water resources management. We suggest two other options : 1. to consider equitable access has a tool to improve the effective use of water for agricul¬tural purposes (limiting the volume of water available per farmer would encourage them to adopt low water consumption crops and water saving technics), 2. to consider more carefully the order of use of the various management tools available and to structure them in a relevant sequence. Here, Political Ecology seems to be a relevant conceptual framework to enter into such a critical reflection, integrating different levels and scales of political asymmetries at the core of environmental issues. Indeed, the understanding of regional water situations and social stumbling blocks needs not only to consider local capabilities and socio-political inequities, but also agro-industrial policy (e.i. cotton) and caste political alliances at a national scale, as well as ideological and narrative struggles or strategical orientations of financial backers at an international level. Our empirical research modestly contributes to the development of such a Political Ecology of water resources development and management.

Population viscosity can promote the evolution of altruistic sterile helpers and eusociality.

Because it increases relatedness between interacting individuals, population viscosity has been proposed to favour the evolution of altruistic helping. However, because it increases local competition between relatives, population viscosity may also act as a brake for the evolution of helping behaviours. In simple models, the kin selected fecundity benefits of helping are exactly cancelled out by the cost of increased competition between relatives when helping occurs after dispersal. This result has lead to the widespread view, especially among people working with social organisms, that special conditions are required for the evolution of altruism. Here, we re-examine this result by constructing a simple population genetic model where we analyse whether the evolution of a sterile worker caste (i.e. an extreme case of altruism) can be selected for by limited dispersal. We show that a sterile worker caste can be selected for even under the simplest life-cycle assumptions. This has relevant consequences for our understanding of the evolution of altruism in social organisms, as many social insects are characterized by limited dispersal and significant genetic population structure.

Is a pre-anaesthetic information form really useful?

BackgroundAll patients should be fully informed about the risks and benefits of anaesthetic procedures before giving a written consent. Moreover, the satisfaction level may vary in proportion to the information given. We aimed to determine, in a single-blind randomized-controlled study, whether an information form given before the pre-anaesthetic consultation could improve perceived information, information gain and satisfaction level.MethodsTwo hundred patients ASA 1-3 scheduled for an elective orthopaedic surgery were randomized into two groups: a group that received an information form before the pre-anaesthetic consultation (IF group) and a control group (no information form). A standardized questionnaire was submitted after the pre-anaesthetic consultation and after the operation. This 17-item questionnaire explored perceived information (five items), information gain (three items) and satisfaction level (nine items). The items of each topic were pooled and compared between groups.ResultsOne hundred and eighty-five patients (92.5%) completed the study. The IF group had better perceived information (IF group 73% vs. control group 63%, P=0.002), higher information gain (IF group 75% vs. control group 62%, P=0.001) and a higher satisfaction level (IF group 95% vs. control group 92%, P=0.048).ConclusionsOur study suggests that an information form given before the pre-anaesthetic consultation enhances perceived information, information gain and satisfaction level.

An international university network for online teaching of pathology in Frenchspeaking countries

Introduction: Building online courses is a highly time consuming task for teachers of a single university. Universities working alone create high-quality courses but often cannot cover all pathological fields. Moreover this often leads to duplication of contents among universities, representing a big waste of teacher time and energy. We initiated in 2011 a French university network for building mutualized online teaching pathology cases, and this network has been extended in 2012 to Quebec and Switzerland. Method: Twenty French universities (see & for details), University Laval in Quebec and University of Lausanne in Switzerland are associated to this project. One e-learning Moodle platform (http://moodle.sorbonne-paris-cite.fr/) contains texts with URL pointing toward virtual slides that are decentralized in several universities. Each university has the responsibility of its own slide scanning, slide storage and online display with virtual slide viewers. The Moodle website is hosted by PRES Sorbonne Paris Cité, and financial supports for hardware have been obtained from UNF3S (http://www.unf3s.org/) and from PRES Sorbonne Paris Cité. Financial support for international fellowships has been obtained from CFQCU (http://www.cfqcu.org/). Results: The Moodle interface has been explained to pathology teachers using web-based conferences with screen sharing. The teachers added then contents such as clinical cases, selfevaluations and other media organized in several sections by student levels and pathological fields. Contents can be used as online learning or online preparation of subsequent courses in classrooms. In autumn 2013, one resident from Quebec spent 6 weeks in France and Switzerland and created original contents in inflammatory skin pathology. These contents are currently being validated by senior teachers and will be opened to pathology residents in spring 2014. All contents of the website can be accessed for free. Most contents just require anonymous connection but some specific fields, especially those containing pictures obtained from patients who agreed for a teaching use only, require personal identification of the students. Also, students have to register to access Moodle tests. All contents are written in French but one case has been translated into English to illustrate this communication (http://moodle.sorbonne-pariscite.fr/mod/page/view.php?id=261) (use "login as a guest"). The Moodle test module allows many types of shared questions, making it easy to create personalized tests. Contents that are opened to students have been validated by an editorial committee composed of colleagues from the participating institutions. Conclusions: Future developments include other international fellowships, the next one being scheduled for one French resident from May to October 2014 in Quebec, with a study program centered on lung and breast pathology. It must be kept in mind that these e-learning programs highly depend on teachers' time, not only at these early steps but also later to update the contents. We believe that funding resident fellowships for developing online pathological teaching contents is a win-win situation, highly beneficial for the resident who will improve his knowledge and way of thinking, highly beneficial for the teachers who will less worry about access rights or image formats, and finally highly beneficial for the students who will get courses fully adapted to their practice.

Studying the molecular causes of ageing in ants

RÉSUMÉ DE THÈSE Au cours de ma thèse, je me suis intéressée aux causes physiologiques du vieillissement en utilisant les fourmis comme modèle. Les trois castes de fourmis - les mâles, les ouvrières et les reines - présentent des longévités très différentes, tout en étant génétiquement identiques. Ceci implique que les différences de longévité sont dues à des variations entre castes dans le pattern d'expression de gènes. Mon travail chez la fourmi a consisté d'une part à mettre en place les outils pour identifier de tels gènes à grande échelle, de l'autre à étudier le rôle de gènes et de mécanismes qui affectent la longévité chez d'autres espèces. Pour identifier de nouveaux gènes potentiellement impliqués dans le vieillissement, nous avons développé des puces à ADN. Cette technique permet la comparaison du niveau d'expression de milliers de gènes entre deux échantillons. L'application de cette méthode aux reines et ouvrières adultes nous a jusqu'à présent permis d'identifier neuf gènes surexprimés chez les reines. Trois d'entre eux sont potentiellement impliqués dans le maintien et la réparation du soma, deux processus qui sont supposés avoir un impact crucial sur la longévité. Parmi les mécanismes impliqués dans le vieillissement chez d'autres espèces, nous nous sommes principalement intéressés aux télomères, qui sont les extrémités des chromosomes. Chez les vertébrés, les télomères se raccourcissent à chaque division cellulaire, entre autres parce que l'ADN polymérase ne peut répliquer cette partie des chromosomes en entier. Or des télomères courts entravent la prolifération des cellules et peuvent même induire l'apoptose, ce qui pourrait se répercuter sur la capacité des organismes à régénérer des tissus. J'ai pu montrer que chez les fourmis mâles (la caste qui vit le moins longtemps) les télomères se raccourcissent beaucoup plus vite que chez les reines et les ouvrières. L'explication la plus plausible pour cette différence est que les mâles, étant adapté à une vie très éphémère, n'investissent qu'un minimum d'énergie dans la machinerie de maintenance qui assure le bon fonctionnement des cellules. Ces résultats sont intéressants car ils permettent pour la première fois de faire le lien entre les théories évolutives du vieillissement et la biologie des télomères. THESIS ABSTRACT During my thesis I used ants as a model to study the proximate (i.e., molecular) causes of ageing and lifespan determination. Ant queens, workers and males differ tremendously in lifespan, although all three castes are genetically identical. Importantly, this implies that genes and molecular pathways responsible for modulating lifespan are regulated in a caste-specific manner. To find new genes potentially involved in ageing, we first constructed 371-gene-cDNA microarrays for the ant L. niger. This molecular tool can be used to survey the relative gene expression levels of two samples for thousands of genes simultaneously. By applying this method to adult queens and workers we identified nine genes that are overexpressed in queens. Three of them are putatively involved in somatic maintenance and repair, two processes that have been previously suggested as important for ageing and lifespan determination. We expect to identify many more candidate genes in the near future by using the 9000-gene fire ant microarrays we have recently developed. We also investigated whether factors linked to ageing in other organisms could affect lifespan determination in ants. One project was on telomeres, the ends of linear chromosomes. For various reasons telomeres shorten with every cell division. Since short telomeres can lead to cellular defects such as impaired cell division, telomeres have been hypothesized as playing a role in ageing. We tested whether telomere length in ant somatic tissues correlates with caste-specific lifespan in young adults. The short-lived L. niger mates did indeed have significantly shorter telomeres than the longer-lived queens and workers, probably because telomere attrition is faster in males than in queens and workers. Queens did not, however, have longer telomeres than the shorter-lived workers. These findings are consistent with the idea that telomere length may play a role in ageing under some circumstances, but they also clearly demonstrate that other factors must be involved. We argue that sex-specific telomere length patterns in ants ultimately reflect adaptive differences in the level of somatic maintenance between males and females, and thus create a link between telomere biology and the evolutionary theory of ageing.

Food allergy: Evaluation of the quality of life in Swiss children

Background: Food allergy in children, an increasingly prevalent disease, significantly affects the quality of life. Its impact can be analyzed by the recently validated French version of the Food Allergy Quality of Life Questionnaire (FAQLQ). Objectives: The aim of our study was to evaluate the quality of life in a small sample of Swiss children with IgE-mediated food allergy. Methods: Information were collected with the questionnaire among 0-12 years old children and their parents during a scheduled allergy visit, and analysed in term of emotional impact, food anxiety and social and food limitations. Patients were divided according to the questionnaire in three age groups: group 1 from 0 to 3 years, group 2 from 4 to 6 years and group 3 from 7 up to 12 years. Results: 30 food allergic patients were included, with a girl/boy ratio of 1:1.14. Median age was 6 years. 56% suffered from or had a history of eczema, 23% of rhino-conjunctivitis, 30% of asthma, and 13% reported a drug allergy. None had insect venom allergy. 57% were known to be allergic to one food, 20% to two foods, 20% to 3 foods and 3% had 3 or more food allergies. Tree nuts (51% of all allergies) as well as eggs (28 %) were the major allergies. Emotional impact had a total score of 1.54 but showed differences between age groups. In group 1 it was lower with 0.23, in group 2 the score was 2.03 and 1.77 in group 3. Food anxiety total score was 1.9; 0.76 in group 1, 2.31 in group 2 and 2.23 in group 3. Social and food limitations showed similar results with a total score of 1.73 and 1.23 in group 1, 2.05 in group 2 and 1.68 for group 3. Conclusion: Food allergy affects the quality of life of Swiss children. Our preliminary results on a small sample are comparable to previously published data. We show that the impact of food allergy on daily life increases when the child starts school and social activities.

Division of labor in insect societies : genetic components and physiological regulation

The shift from solitary to social organisms constitutes one of the major transitions in evolution. The highest level of sociality is found in social insects (ants, termites and some species of bees and wasps). Division of labor is central to the organization of insect societies and is thought to be at the root of their ecological success. There are two main levels of division of labor in social insect colonies. The first relates to reproduction and involves the coexistence of queen and worker castes: while reproduction is usually monopolized by one or several queens, functionally sterile workers perform all the tasks to maintain the colony, such as nest building, foraging or brood care. The second level of division of labor, relating to such non-reproductive duties, is characterized by the performance of different tasks or roles by different groups of workers. This PhD aims to better understand the mechanisms underlying division of labor in insect societies, by investigating how genes and physiology influence caste determination and worker behavior in ants. In the first axis of this PhD, we studied the nature of genetic effects on division of labor. We used the Argentine ant Linepithema humile to conduct controlled crosses in the laboratory, which revealed the existence of non-additive genetic effects, such as parent-of-origin and genetic compatibility effects, on caste determination and worker behavior. In the second axis, we focused on the physiological regulation of division of labor. Using Pogonomyrmex seed- harvester ants, we performed experimental manipulation of hibernation, hormonal treatments, gene expression analyses and protein quantification to identify the physiological pathways regulating maternal effects on caste determination. Finally, comparing gene expression between nurses and foragers allowed us to reveal the association between vitellogenin and worker behavior in Pogonomyrmex ants. This PhD provides important insights into the role of genes and physiology in the regulation of division of labor in social insect colonies, helping to better understand the organization, evolution and ecological success of insect societies. - L'une des principales transitions évolutives est le passage de la vie solitaire à la vie sociale. La socialité atteint son paroxysme chez les insectes sociaux que sont les fourmis, les termites et certaines espèces d'abeilles et de guêpes. La division du travail est la clé de voûte de l'organisation de ces sociétés d'insectes et la raison principale de leur succès écologique. La division du travail s'effectue à deux niveaux dans les colonies d'insectes sociaux. Le premier niveau concerne la reproduction et implique la coexistence de deux castes : les reines et les ouvrières. Tandis que la reproduction est le plus souvent monopolisée par une ou plusieurs reines, les ouvrières stériles effectuent les tâches nécessaires au bon fonctionnement de la colonie, telles que la construction du nid, la recherche de nourriture ou le soin au couvain. Le second niveau de division du travail, qui concerne les tâches autres que la reproduction, implique la réalisation de différents travaux par différents groupes d'ouvrières. Le but de ce doctorat est de mieux comprendre les mécanismes sous-jacents de la division du travail dans les sociétés d'insectes en étudiant comment les gènes et la physiologie influencent la détermination de la caste et le comportement des ouvrières chez les fourmis. Dans le premier axe de ce doctorat, nous avons étudié la nature des influences génétiques sur la division du travail. Nous avons utilisé la fourmi d'Argentine, Linepithema humile, pour effectuer des croisements contrôlés en laboratoire. Cette méthode nous a permis de révéler l'existence d'influences génétiques non additives, telles que des influences dépendantes de l'origine parentale ou des effets de compatibilité génétique, sur la détermination de la caste et le comportement des ouvrières. Dans le second axe, nous nous sommes intéressés à la régulation physiologique de la division du travail. Nous avons utilisé des fourmis moissonneuses du genre Pogonomyrmex pour effectuer des hibernations artificieHes, des traitements hormonaux, des analyses d'expression de gènes et des mesures de vitellogénine, ce qui nous a permis d'identifier les mécanismes physiologiques régulant les effets maternels sur la détermination de la caste. Enfin, la comparaison d'expression de gènes entre nourrices et fourrageuses suggère un rôle de la vitellogénine dans la régulation du comportement des ouvrières chez les fourmis moissonneuses. En détaillant les influences des gènes et de la physiologie dans la régulation de la division du travail dans les colonies d'insectes sociaux, ce doctorat fournit d'importantes informations permettant de mieux comprendre l'organisation, l'évolution et le succès écologique des sociétés d'insectes.

Methylprednisolone concentrations in the vitreous and the serum after pulse therapy.

PURPOSE: Intravenous (i.v.) pulse of corticosteroids has been used to treat severe eye inflammation from different origins. Whether such large doses result in vitreous levels that differ either in magnitude or duration from more conventional corticotherapy remain unsolved issues. The authors therefore determined levels of methylprednisolone hemisuccinate and methylprednisolone in the vitreous and serum of patients at different times after a single i.v. perfusion of methylprednisolone hemisuccinate. METHODS: Fifty patients scheduled for a first vitrectomy received an i.v. injection of 500 mg hemisuccinate methylprednisolone at different times before surgery (from 15-24 hours). Patients were divided into two groups: those with (n = 21) and without (n = 29) retinal detachment (RD). Pure vitreous samples were analyzed by high-pressure liquid chromatography. RESULTS: Both the ester and the nonester methylprednisolone forms were sampled in the vitreous, showing a slower rate of hydrolysis compared to the serum. On average, the highest concentration of total methylprednisolone in the vitreous was found at 2.5 hours and rapidly decreased for the group of patients with RD. In the group of patients without RD, the highest concentration was reached at 6 hours and then slowly decreased. The antiinflammatory potency in the nondetached retina eyes was approximately 500 times more than in the physiologic vitreous, but despite the route of administration (i.v. or oral), only 1/10 of the corticosteroid serum concentration was measured in the vitreous. CONCLUSION: High concentration of methylprednisolone is achieved by i.v. pulse therapy without changing the kinetic of entry in the vitreous of nondetached retina eyes when compared to conventional oral corticotherapy. Hydrolysis occurs in the vitreous resulting in high rate of active form. Pulse therapy could be considered in cases of severe ocular inflammation involving the posterior segment of the eye.