Targeting Cytokine Systems to Achieve Neuroprotection: Experimental Models of Seizures and Neurodegeneration

This study investigated whether IL-1β and TNF-α have a role in the pathophysiology of seizures by altering neuronal excitability and cell survival and also probed new targets to achieve an effective anticonvulsive action. The first set of experiments evaluated if acute and spontaneous seizures can be effectively inhibited by blocking the brain production of IL-1β using a selective inhibitor of caspase-1, the key enzyme specifically involved in the production of the releasable and biologically active form of IL-1β. Caspase-1 inhibition significantly reduced the number and the total time spent in seizures, indicating that this treatment represents an effective and novel anticonvulsive strategy. The second set of experiments investigated the intracellular pathway involved in the IL-1β proconvulsant actions which appear to occur via a novel non-transcriptional pathway: namely, the IL-1β-mediated activation of neutral-sphingomyelinase, the production of ceramide and the subsequent phosphorylation of Src-family of tyrosine kinases and the target receptor protein NR2B subunit of the NMDA receptor, resulting in the potentiation of NMDA function. This fast post-translational effect of IL-1β represents a novel and non-conventional pathway by which inflammatory molecules produced in epileptic tissue can affect neurotransmission. Then, this work demonstrated that a brief pro-inflammatory stimulus, characterized by the activation of microglia and subsequent lasting release of critical concentrations of IL-1β, primes neuronal vulnerability to a subsequent excitotoxic insult, highlighting one mechanism by which a pre-existent pro-inflammatory state may increase hippocampal neuronal susceptibility to the excitotoxic damage associated with seizures. Thus, pharmacological approaches specifically targeted to block the overproduction of IL-1β and its functions in diseased conditions may represent new, nonconventional strategies for the treatment of seizure disorders, which are refractory to classical anticonvulsant treatments. The second part of this thesis demonstrated that TNF-α significantly decreases epileptic activity by specifically acting on neuronal p75 receptors. The actions of TNF-α on neuronal excitability strictly depend on whether p55 or p75 receptors are preferentially involved and appear to be mediated also by changes in the assembly of glutamate receptor subunits. These novel functional glia-neuronal interactions add important insights into the mechanism of ictogenesis and seizure-associated neuronal cell death, highlighting innovative pharmacological strategies to block the activation of cytokine-mediated signalling in diseased conditions

Nanotechnology in radiation oncology: The need for implantable nano dosimeters for in-vivo real time measurements

International audienceRapidly advancing technology provides successive generations of irradiation techniques and modalities of cancer treatment in radiation oncology. Most of these techniques are able to deliver higher doses per fraction than the standard 2 Gy per day. The complexity of these new techniques involves hundreds of parameters for the delivery of each beam making quality assurance increasingly demanding. A direct assessment of the "final product", namely the absorbed dose, would be extremely useful if easy to obtain. Thus, a real need exists for dosimeters able to provide direct and real time measurements within the target volume. Nanotechnology is a relatively new field, and in some ways raises new technological aspirations, especially in the field of medical applications for cancer treatment. In this paper we argue the need for an implantable " nano-dosimeter " based on nanotechnology to monitor the delivered dose, combining all the ideal features such a future tool should have for quality assurance in radiation oncology

Autour des instruments de musique, une recherche pluridisciplinaire

Entre septembre 2015 et février 2016, dans le cadre du programme Geste-Acoustique-Musique (GeAcMus), initié par Sorbonne Universités, nous avons formé une équipe composée de chercheurs en sciences humaines, de chercheurs en sciences exactes et de musiciens profes- sionnels, pour mieux dévoiler, dans différentes cultures, les interactions entre le geste de l’instrumentiste, les propriétés mécaniques de son instrument et la musique interprétée. Pour ce domaine de recherche émergent, l’interdisciplinarité nous a permis d’apporter de nouveaux regards, plus complets, sur les instruments choisis. Notre partie du projet GeAcMus, centrée sur des instruments à vent (les flûtes et les cornemuses), était dirigée par une équipe comprenant des acousti- ciens, des ingénieurs et une ethnomusicologue. Tous musiciens, nous avons mis nos compétences au service de trois différents projets développés en parallèle, choisis selon les centres d’intérêt de chacun

Les enjeux de l’hadronthérapie par ions carbone

National audienceL’ambition de doter la France d’un centre de traitement des tumeurs par faisceaux d’ions carbone est née, à la fin des années 1990, de la rencontre à l’Université Claude Bernard Lyon 1 de quelques médecins et physiciens, convaincus que la France avait toutes les capacités médicales et scientifiques pour initier un tel programme. Ce projet de « carbonethérapie » prit le nom de projet ETOILE (Espace de Traitement Oncologique par Ions Légers en Europe) au début des années 2000. Pour comprendre pourquoi il n’a pas été réalisé et évaluer les chances pour qu’il le soit un jour, il faut analyser les enjeux, les difficultés et les avantages de la carbonethérapie, comparée à la protonthérapie et aux formes les plus avancées de la radiothérapie

Castelo Branco, Salwa El Shawan y Moreno Fernández, Susana. 2018. Music in Portugal and Spain: Experiencing Music, Expressing Culture. Oxford: Oxford University Press, 137pp., CD and a companion website

Part of the Global Music Series, Music in Portugal and Spain: Experiencing Music, Expressing Culture is written by two of the leading scholars in music from Spain and Portugal, two countries that have experienced similar and even at times joint historical trajectories. As ‘the first textbook that deals with the musics of Portugal and Spain comparatively’ (pxii), we are offered a more comprehensive musical and cultural overview than a textbook dealing with either of these geographical areas separately

#NoBordersTour. Världens Band: creating and performing music across borders

Moving away from a university context, and within a framework of intercultural (ed. Burnard &co. 2016), performance (ed. Solis 2004) and social change (Baker 2014) studies, this article will explore the constant border negotiations of a professional international world music band, formed by thirteen musicians from seven countries: India, Senegal, Sweden, France, England and Scotland. Imagined as a utopian social experiment by two Swedish brothers in 2012, Världens Band (the World’s Band) quickly grew beyond the project phase and established itself as a group, performing self-branded ‘transglobal roots fusion’ music. With six different nationalities and the will to create music that both reflects and transcends them, borders are a constant source of negotiation for the musicians in musical, political and touring contexts. Musically, the band chooses to represent a united ensemble featuring musicians rather than ‘countries’. Although each individual strongly represents his or her own tradition, rehearsals are a vital space where musical negotiation and collective arranging shape pieces, respecting both cultural backgrounds and the will to collaborate across borders. The inclusiveness message featured in the music becomes a strong yet consciously unvoiced political message on stage of an ideal world where multiculturalism is a strength rather than a divisive force. Politically, the band reinforced its inclusiveness message over time, namely during the 2015 refugee crisis that coincided with a 10-week tour branded ‘No Borders Tour’. Since, performing for schools and refugee audiences is fully integrated into their schedules with the ideology of counteracting the growing nationalist movements in Scandinavia and the rest of Europe. Off stage, borders continue to impact the musicians. Not only do visas have to be issued and frontiers crossed, sometimes unsuccessfully, there is also a constant cultural dialogue between the band members as they learn to understand each other. Verbal communication then becomes key and the leadership of the band manager becomes at times crucial as space is made for voicing opinions and thoughts, resulting in a better understanding of each individual. Through all these different aspects, Världens Band offers a platform for rethinking intercultural collaboration within a professional context, beyond the popular one-off projects or groups with a high turnover (see Hughes 2004)

Statistical evaluation of dosimetric differences changes between the Modified Batho's density correction method and the Anisotropic Analytical Algorithm for clinical practice

Purpose: The aim of this work was to assess and to quantify, for clinical practice, the differences in computed doses using two types of dose calculation algorithm for the heterogeneity correction including target volumes and organs at risk (OARs).Methods: 35 patients having lung, breast, spine, head & neck, brain and pelvic tumors, were studied. For each patient, 2 treatment plans were generated. In plan 1, the dose was calculated using the Modified Batho's (MB) density correction method integrated in the Pencil Beam Convolution algorithm. In plan 2, the dose was calculated using the Anisotropic Analytical Algorithm (AAA). To compare the two plans a dosimetric analysis was carried out including cumulative and differential dose volume histograms (DVH), coverage index, and conformity index. Wilcoxon signed rank and Spearman’s tests were used to calculate p-values and correlation coefficients (r), respectively. Bootstrap simulation with 1000 random samplings was used to calculate the 95% confidence interval (95% CI).Results: The analysis of DVH showed that the AAA method calculated significantly higher doses for OARs for all cancer sites and lower doses for target volumes, especially for targets located in lung, with p < 0.05. The data demonstrated a strong correlation between MB and AAA for all cancer sites with r > 0.9.Conclusion: This study confirms that using the AAA integrated into Eclipse® TPS, the calculated dose will be increased to OARs, and reduced to target volumes. Thus, when changing from the MB algorithm to AAA, attention should be paid to avoid any bias of over/under estimating the dose given by AAA and to hold discussions between physicists and oncologists regarding any necessary modification in the prescription method

Irradiation de métastases cérébrales en conditions stéréotaxiques par rayonnement synchrotron (évaluation dosimétrique d une technique innovante)

CONTEXTE: Ces dernières années, des techniques d irradiation innovantes sont apparues avec la RC3D, la STEREO et la RCMI. L ESRF dispose d une source de rayons X permettant de délivrer des irradiations d intérêt médical, la SSRT. OBJECTIFS: Effectuer une comparaison dosimétrique entre ces techniques et la SSRT en absence puis en présence de produit de contraste iodé pour l irradiation stéréotaxique d une métastase cérébrale. Effectuer une comparaison dosimétrique entre la STEREO et la SSRT/PdCI pour 5 patientes atteintes de métastases cérébrales et évaluer l impact des variations liées aux lésions. PATIENTS ET MÉTHODE: Cette étude repose sur 5 patientes âgées de 34 à 70 ans. La prescription d une dose de 23,1 Gy s est effectuée sur l isodose 70% avec une dose à l isocentre de 33 Gy. La comparaison s est portée sur la conformation de la dose et sur l évaluation des doses reçues par les organes à risque. RÉSULTATS: Le traitement le plus optimal pour l irradiation stéréotaxique d une métastase cérébrale unique semble être la STEREO. La SSRT/PdCI est très proche de la STEREO avec une couverture des volumes cibles et une préservation des OAR adaptées. Les différences de dose observées sont corrélées à l hétérogénéité de la prise de contraste tumorale. L inconvénient de la SSRT reste la surdose délivrée à l os. CONCLUSION: La STEREO doit rester la référence du traitement des métastases cérébrales uniques. La SSRT en présence d éléments lourds apparaît être une technique prometteuse pour le traitement de lésions de petite taille, présentant un rehaussement homogène, une localisation intra-parenchymateuse centrale, à distance des structures osseuses et des gros vaisseaux.BACKGROUND: In recent years, innovative radiation techniques have emerged with RC3D, STEREO and IMRT. ESRF has an X-ray source for delivering medical radiation of interest, the SSRT. OBJECTIVES: Perform a dosimetric comparison between these techniques and the SSRT in the absence and in the presence of iodinated contrast agent for stereotactic irradiation of brain metastasis. Perform a dosimetric comparison between STEREO and SSRT / PdCl for 5 patients with brain metastases and evaluate the impact of changes related injuries. PATIENTS AND METHODS: This study is based on five patients aged 34 to 70 years. Prescribing a dose of 23.1 Gy was performed on the 70% isodose with a dose of 33 Gy to the isocenter. The comparison is focused on the shape of the dose and the evaluation of doses to organs at risk. RESULTS: The most optimal treatment for stereotactic irradiation of a single brain metastasis appears to be STEREO. The SSRT / PdCI is very close to the STEREO with coverage of target volumes and preservation of SRO adapted. The observed differences in dose are correlated with the heterogeneity of the tumor contrast enhancement. The disadvantage of the SSRT remains overdose delivered to the bone. CONCLUSION: STEREO must remain the main treatment for single brain metastases. The SSRT in the presence of heavy elements appears to be a promising technique for the treatment of small lesions, with a homogeneous enhancement, a intra-parenchymal central location, away from the bone structures and great vessels.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

Fourth International Bagpipe Conference

The International Bagpipe Organisation organised the Fourth International Bagpipe Conference to mark International Bagpipe Day 2018 (10 March), a celebration of the world’s diverse bagpipes and bagpiping traditions. Following the success of previous conferences, the upcoming event spread over three days, starting on Friday evening with an opening concert and ending on Sunday afternoon. The conference was held in Palma, Mallorca, where there is a rich and unbroken piping tradition. The conferences are a productive and welcoming platform for all people interested in the study of bagpipes: musicologists, ethnomusicologists, music experts, instrument makers, musicians, composers, dancers and music lovers. This event is an exciting interdisciplinary opportunity to discuss various questions relating to the study of bagpipes both today and historically. All three days are open to the general public and bagpipe enthusiasts are encouraged to attend. As the conference will be held in Catalan speaking territory, papers were welcomed in English, Spanish and Catalan. Simultaneous translation from English to Spanish and Spanish to English was provide

The choice of statistical methods for comparisons of dosimetric data in radiotherapy

Purpose: Novel irradiation techniques are continuously introduced in radiotherapy to optimize the accuracy, the security and the clinical outcome of treatments. These changes could raise the question of discontinuity in dosimetric presentation and the subsequent need for practice adjustments in case of significant modifications. This study proposes a comprehensive approach to compare different techniques and tests whether their respective dose calculation algorithms give rise to statistically significant differences in the treatment doses for the patient. Methods: Statistical investigation principles are presented in the framework of a clinical example based on 62 fields of radiotherapy for lung cancer. The delivered doses in monitor units were calculated using three different dose calculation methods: the reference method accounts the dose without tissues density corrections using Pencil Beam Convolution (PBC) algorithm, whereas new methods calculate the dose with tissues density correction for 1D and 3D using Modified Batho (MB) method and Equivalent Tissue air ratio (ETAR) method, respectively. The normality of the data and the homogeneity of variance between groups were tested using Shapiro-Wilks and Levene test, respectively, then non-parametric statistical tests were performed. Specifically, the dose means estimated by the different calculation methods were compared using Friedman’s test and Wilcoxon signed-rank test. In addition, the correlation between the doses calculated by the three methods was assessed using Spearman’s rank and Kendall’s rank tests Results: The Friedman’s test showed a significant effect on the calculation method for the delivered dose of lung cancer patients (p 0.001). The density correction methods yielded to lower doses as compared to PBC by on average (−5 ± 4.4 SD) for MB and (−4.7 ± 5 SD) for ETAR. Post-hoc Wilcoxon signed-rank test of paired comparisons indicated that the delivered dose was significantly reduced using density-corrected methods as compared to the reference method. Spearman’s and Kendall’s rank tests indicated a positive correlation between the doses calculated with the different methods. Conclusion: This paper illustrates and justifies the use of statistical tests and graphical representations for dosimetric comparisons in radiotherapy. The statistical analysis shows the significance of dose differences resulting from two or more techniques in radiotherapy