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Oncogenic fusion proteins generated by chromosomal translocations play major roles in cancer. Among them, fusions between EWSR1 and transcription factors generate oncogenes with powerful chromatin regulatory activities, capable of establishing complex gene expression programs in permissive precursor cells. Here we define the epigenetic and 3D connectivity landscape of Clear Cell Sarcoma, an aggressive cancer driven by the EWSR1-ATF1 fusion gene. We find that EWSR1-ATF1 displays a distinct DNA binding pattern that requires the EWSR1 domain and promotes ATF1 retargeting to new distal sites, leading to chromatin activation and the establishment of a 3D network that controls oncogenic and differentiation signatures observed in primary CCS tumors. Conversely, EWSR1-ATF1 depletion results in a marked reconfiguration of 3D connectivity, including the emergence of regulatory circuits that promote neural crest-related developmental programs. Taken together, our study elucidates the epigenetic mechanisms utilized by EWSR1-ATF1 to establish regulatory networks in CCS, and points to precursor cells in the neural crest lineage as candidate cells of origin for these tumors.

Within the framework of its partnership and its involvement in the "self-recovery" working group of the GSC, CRAterre and its partners have been working for several years to develop and disseminate a method to identify and enhance the value of local construction cultures para-disaster, if necessary by revisiting them, in order to propose improvements during reconstruction or development projects in terms of housing.This has resulted in the launch,first and foremost with IFRC2,and further with other international and national agencies, of a series of highly innovative documents, the shelter response profile(SRP), initially called baseline data on local building culture & coping strategy. They provide baseline data on building cultures and local socio-cultural strategies for resilience that are useful to consider when designing and implementing shelterand disaster risk reduction programs.The objective is to help all actors to identify and raise awareness among their partners of the relevance, potential and limitations of local construction methods so that they can be better taken into account in projects, particularly in post-disaster recovery / reconstruction. This profileis intended to be a working basis for the elaboration of strategies specific to each project taking into account the local potential as much as possible.After the success and limitationsof the first profilein Fijiin 2016, several profileswere subsequently produced at therequest of the GlobalShelter Cluster through in-country shelter clusterssetup to respond to natural or human-made crises or disasters: Ethiopia, DRC, Haiti, Bangladesh, Ecuador, etc.

Aim: Quantitative endogenous steroid profiling in blood appears as a complementary approach to the urinary module of the World Anti-Doping Agency's Athlete Biological Passport Steroidal Module for the detection of testosterone doping. To refine this approach further, a UHPLC–MS/MS method was developed for the simultaneous determination of 14 free and 14 conjugated steroids in serum. Results: The method was validated for quantitative purposes with satisfactory results in terms of selectivity, linearity range, trueness, precision and combined uncertainty (

Within the framework of its partnership and its involvement in the "self-recovery" working group of the GSC, CRAterre and its partners have been working for several years to develop and disseminate a method to identify and enhance the value of local construction cultures para-disaster, if necessary by revisiting them, in order to propose improvements during reconstruction or development projects in terms of housing.This has resulted in the launch,first and foremost with IFRC2,and further with other international and national agencies, of a series of highly innovative documents, the shelter response profile(SRP), initially called baseline data on local building culture & coping strategy. They provide baseline data on building cultures and local socio-cultural strategies for resilience that are useful to consider when designing and implementing shelterand disaster risk reduction programs.The objective is to help all actors to identify and raise awareness among their partners of the relevance, potential and limitations of local construction methods so that they can be better taken into account in projects, particularly in post-disaster recovery / reconstruction. This profileis intended to be a working basis for the elaboration of strategies specific to each project taking into account the local potential as much as possible.After the success and limitationsof the first profilein Fijiin 2016, several profileswere subsequently produced at therequest of the GlobalShelter Cluster through in-country shelter clusterssetup to respond to natural or human-made crises or disasters: Ethiopia, DRC, Haiti, Bangladesh, Ecuador, etc.

Croisant la psychologie socioculturelle, la clinique de l’activite et l’analyse du discours, cette etude porte sur une seance d’education therapeutique du patient (ETP) reunissant une infirmiere, Ines, et un adolescent vivant avec le diabete. Elle vise d’une part, a analyser les mecanismes d’intercomprehension et d’ajustement mutuel en jeu dans l’explication, d’autre part a susciter le developpement professionnel. Elle analyse une sequence explicative puis recourt a une methode qui confronte la professionnelle a son activite (methode d’autoconfrontation simple et croisee). Les resultats montrent que dans la seance d’ETP, le discours medical qui emerge instaure une forte asymetrie entre les interactants et laisse planer le doute sur la comprehension du patient. Alors que dans l’autoconfrontation simple, Ines s’interroge sur la comprehension et l’etat emotionnel du patient, dans l’autoconfrontation croisee, les commentaires de sa collegue l’amenent a se souvenir d’une situation professionnelle precedente et a s’interroger sur ses propres etats emotionnels et interpretations. La methode d’autoconfrontation semble apte a saisir les mecanismes psychologiques sous-jacents aux explications fournies par les professionnels et a susciter une forme de developpement professionnel.

Cancer stem cells (CSCs) can drive tumor growth, and their maintenance may rely on post-transcriptional regulation of gene expression, including that mediated by microRNAs (miRNAs). The let-7 miRNA family has been shown to induce differentiation by silencing stem cell programs. Let-7-mediated target gene suppression is prevented by LIN28A/B, which reduce let-7 biogenesis in normal embryonic and some cancer stem cells and ensure maintenance of stemness. Here, we find that glioblastoma stem cells (GSCs) lack LIN28 and express both let-7 and their target genes, suggesting LIN28-independent protection from let-7 silencing. Using photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP), we show that insulin-like growth factor 2 mRNA-binding protein 2 (IMP2) binds to let-7 miRNA recognition elements (MREs) and prevents let-7 target gene silencing. Our observations define the RNA-binding repertoire of IMP2 and identify a mechanism whereby it supports GSC and neural stem cell specification., Cell Reports, 15 (8), ISSN:2666-3864, ISSN:2211-1247

International audience; Over the past 15 years, a number of housing projects undertaken in post-disaster situations have adopted a “local building cultures” approach to efficiently support the initiatives of affected populations, regardless of their location or origin.This becomes even more pertinent when working in rural areas where, often, populations benefit from the ancestral experience of living in their lands and so, possess a rich knowledge of theirenvironment and traditional housing, and of their strengths and weaknesses facing natural hazards.Both reconstruction projects presented in this booklet, undertaken in the aftermath of typhoon Yolanda, are a good illustration of this potential. Moreover, they highlight how such an approach favors the establishment (or rather the re-establishment) of resilience within local communities while also offering a vision for local development and well-being in continuity with the local culture, a principle deemed as strongly valuable within the international humanitarian community as a whole.

International audience

Despite the relevance of this research topic from a public health perspective, there is currently a lack of objective data on European adolescents' sport activity, notably the associations between their sport habits and their health attitudes and behaviours, which may have important consequences both in terms of somatic (cardiovascular) health and mental health. The objective of the present study was to determine the direction and strength of the associations between the frequency of sport and health variables; in particular, perceptions of health, self image, substance use and experimental behaviours. Data were collected as part of the 1993 Swiss Multicentric Adolescent Survey on Health. In this survey, anonymous self-administered questionnaires were distributed to a national representative sample of 10,000 in-school adolescents (15-20 years of age). Univariate analyses explored the relationships between the level of sport activity and health variables; then logistic regression analyses examined the strength of these relationships. According to the results, half of the sample do sports more than twice a week, boys more often as part of a sports club. Differences between non-athletic and athletic adolescents describe the latter as having less somatic complaints, more confidence in their future health, a better body image, a lesser tendency to attempt suicide, a higher frequency of use of the car seat belt, and a lower use of tobacco, wine and marijuana. Links between the frequency of sport activity and the locus of control related to health, general satisfaction with life or sexual behaviours are less strong. It must be noticed that the cross-sectional data collection precludes the establishment of a causal relationship between exercise and health behaviours. However, the existing links underline the coexistence of positive health characteristics and sport activity, suggesting that an incitement to get involved in physical activity may be a necessary component of a comprehensive prevention approach among adolescents. Language: en

International audience; This booklet has been prepared by CRAterre, IFRC and SC-CF and several of their partners. It is part of a set of tools now developed within the framework of a working group (leaded by CARE and CRAterre) within the Global Shelter Cluster to enhance the appreciation of local practices developed by communities to adapt their housing / settlements to their specific environment, including risk preparedness. It presents a series of worldwide examples of local techniques, know-how and knowledge that can be used in reducing housing vulnerability. Though, rather than being a catalogue, it has been conceived as an eyeopener for field operators. The idea is that, with these examples in mind, they will have a sharpened capacity to identify such local solutions during preliminary field inspections. With basic information on why and how these practices are relevant, it is expected that at least those with higher potential are fully reused in habitat projects, both in post disaster and preparedness situations. These solutions being local, they can be implemented with local resources and so, offer large potential for wide application. Overall, that process gives more chance to provide durable benefits and enhanced resilience capacity for local communities while making sure that the qualities of local architecture are preserved. Moreover, it is also hoped that the scientific community will be encouraged to work on their understanding and retro-engineering for adaptation to today’s socio-economic, cultural and environmental context so as to go further in building back safer processes towards more efficiency in recovery and further, sustainable development.

ELAVL3 is an RNA-binding protein, specifically expressed in terminally differentiated neurons. It is necessary for neuron differentiation and maintenance as well as for neuronal plasticity and memory. Bioinformatic analysis, based on The Cancer Genome Atlas data, showed that ELAVL3 expression is increased in gliobastoma multiforme (GBM) of the proneural subtype. It also revealed strong correlation between ELAVL3 and proneural signature gene expression. Those results suggest that the protein might be implicated in GBM development. However, because the role of ELAVL3 in malignant cells has not yet been investigated, it is not clear whether the increased protein expression is necessary for malignant cell tumoregenicity or if it is simply a byproduct of the expression of proneural genes. This study aims to assess the importance of the increased expression of ELAVL3 in proneural GBM stem cells (GSCs) and to clarify the putative role of the protein in the development of this malignancy. First of all, the ELAVL3 expression was determined in GSCs grown both as spheroids and as differentiated adherent cells. Then, its expression was suppressed in GSCs. Those cells were then used to perform a proliferation assay and injected as xenografts into mice, in an attempt to better understand ELAVL3 function. The results of the in vitro experiments showed that the ELAVL3 expression is higher in proneural GSCs compared to stem cells of the other subtypes, which is in agreement with the results of the bioinformatic data analysis. Proliferation assays also showed that non-ELAVL3 expressing cells have a lower proliferation rate than ELAVL3 expressing cells. Unfortunately, those results could not be confirmed by the results of the xenograft injections, due to the lack of data yielded by in vivo experimentation. The results showed aincreased expression of ELAVL3 in proneural GBM stem cells that has never been described before. It also revealed involvement of the protein in cell proliferation, thus offering potential new perspectives regarding its function and its implication in tumorigenesis. Further studies will be needed to confirm these findings and to establish the exact function of ELAVL3 proneural glioblastoma.

The development of a set of tools to enhance appreciation of local practices developed by communities regarding settlements and risks is an initiative that aims to promote context-based strategies for responding efficiently and adequately to habitat improvement and vulnerability reduction needs. This guide offers a methodological and operational support for decision-making and practices towards approaches and actions deeply rooted in local contexts. It is a practical tool that provides detailed explanation on planning, preparing and undertaking field assessments of local practices related to habitat and risks. It refers to a participatory approach suitable for, and adapted to, various geographical, cultural and risk-prone areas. By supporting habitat assessment in all its different aspects, it also fosters links between programmes, providing clues and keys to define and implement coherent projects including income generating activities, livelihood, health and other related sectors. The necessary investment to be taken into account in project planning to achieve the basic step described in this booklet will result in huge savings, as logistical issues will be drastically reduced during the project implementation. It is a worthwhile investment that will lead to decisions ensuring more benefits to the affected communities, including a long-term enhancement of their resilience capacity, Cet ouvrage s'adresse aux responsables de projets et aux preneurs de décisions. L'auteur explique tout d'abord la démarche de projet respectueuse des cultures constructives. L'auteur présente ensuite une méthode d'évaluation des cultures constructives locales et expose l'importance de celle-ci dans un projet

International audience; The development of a set of tools to enhance appreciation of local practices developed by communities regarding settlements and risks is an initiative that aims to promote context-based strategies for responding efficiently and adequately to habitat improvement and vulnerability reduction needs. This guide offers a methodological and operational support for decision-making and practices towards approaches and actions deeply rooted in local contexts. It is a practical tool that provides detailed explanation on planning, preparing and undertaking field assessments of local practices related to habitat and risks. It refers to a participatory approach suitable for, and adapted to, various geographical, cultural and risk-prone areas. By supporting habitat assessment in all its different aspects, it also fosters links between programmes, providing clues and keys to define and implement coherent projects including income generating activities, livelihood, health and other related sectors. The necessary investment to be taken into account in project planning to achieve the basic step described in this booklet will result in huge savings, as logistical issues will be drastically reduced during the project implementation. It is a worthwhile investment that will lead to decisions ensuring more benefits to the affected communities, including a long-term enhancement of their resilience capacity; Cet ouvrage s'adresse aux responsables de projets et aux preneurs de décisions. L'auteur explique tout d'abord la démarche de projet respectueuse des cultures constructives. L'auteur présente ensuite une méthode d'évaluation des cultures constructives locales et expose l'importance de celle-ci dans un projet

BACKGROUND AND OBJECTIVES Evaluation of glomerular hyperfiltration (GH) is difficult; the variable reported definitions impede comparisons between studies. A clear and universal definition of GH would help in comparing results of trials aimed at reducing GH. This study assessed how GH is measured and defined in the literature. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Three databases (Embase, MEDLINE, CINAHL) were systematically searched using the terms "hyperfiltration" or "glomerular hyperfiltration". All studies reporting a GH threshold or studying the effect of a high GFR in a continuous manner against another outcome of interest were included. RESULTS The literature search was performed from November 2012 to February 2013 and updated in August 2014. From 2013 retrieved studies, 405 studies were included. Threshold use to define GH was reported in 55.6% of studies. Of these, 88.4% used a single threshold and 11.6% used numerous thresholds adapted to participant sex or age. In 29.8% of the studies, the choice of a GH threshold was not based on a control group or literature references. After 2004, the use of GH threshold use increased (P

The metabolic effect of multiple oral testosterone undecanoate (TU) doses over 4 weeks was assessed in seven voluntary men. The protocol was designed to detect accumulation of the substance by choosing the appropriate spot urines collections time and to study the urinary clearance of the substance after weeks of treatment. Urines were analysed by a new GC/C/isotope ratio mass spectrometry (IRMS) method to establish the delta(13)C-values of testosterone metabolites (androsterone and etiocholanolone) together with an endogenous reference compound (16(5alpha)-androsten-3alpha-ol). The significant differences in inter-individual metabolism following TU intake was illustrated by large variations in delta(13)C-values of both T metabolites (maximum Deltadelta(13)C-values = 5.5 per thousand), as well as by very stable longitudinal T/E profiles and carbon isotopic ratios in the first hours following administration. According to T/E ratios and delta(13)C-values, the washout period after 80 mg TU intake was less than 48 h for all subjects and no accumulation phenomenon was observed upon chronic oral administration.

Background: Nandrolone is one of the most abused anabolic steroids, and its use in doping is increasing, as revealed by numerous positive cases during recent years in various sports. Different authors have reported the possible natural production of nandrolone metabolites in humans, and some of these authors argued that exhaustive exercise could increase nandrolone production in the body or induce dehydration and consequently lead to an increase of nandrolone metabolites in urine.Methods: Volunteers (n = 22) ingested two 25-mg doses of [13C]nandrolone at 24-h intervals and collected urine specimens for 5 days. The labeled nandrolone metabolites 19-norandrosterone and 19-noretiocholanolone were identified and quantified by gas chromatography–mass spectrometry.Results: Interindividual variability was observed in nandrolone excretion patterns and kinetics, as well as for the noretiocholanolone:norandrosterone ratio. The amounts of nandrolone metabolites measured at the excretion peak varied between 1180 and 38 661 μg/L for norandrosterone and 576 and 12 328 μg/L for noretiocholanolone. At the end of the excretion period, the noretiocholanolone:norandrosterone ratio was sometimes >1. The analysis of numerous spot-urine samples allowed the determination of an acceptable correlation between urinary creatinine and specific gravity for placebo- and steroid-treated individuals: y = 0.0052ln(x) + 1.0178 (r2 = 0.8142) and y = 0.0068ln(x) + 1.0172 (r2 = 0.7730), respectively.Conclusions: The excretion kinetics and patterns of labeled nandrolone show interindividual variability. More investigations are currently underway to estimate the influence of exhaustive exercises on excretion of labeled nandrolone metabolites in urine.

Biometric status, cardiovascular endurance, strength, speed, flexibility, and coordination were assessed in a cross-sectional survey involving 3,540 Swiss boys and girls, aged 9 to 19. Strength and endurance were better among boys, whereas girls displayed better flexibility. Most of the performances among girls did not change from 14 years onwards, while boys exhibited better performances after 15–16 years. The coefficients of correlation between the tests varied from as low as .16 (NS) to .63 (p < .01). Multiple regression analyses showed that height, weight, and chronological and biological age altogether were independently related to the performance on most of the tests. Fitness is a multidimensional concept that not only evolves with chronological age but also depends on biometrical characteristics such as pubertal stage, height, and weight.

Several physical, psychological and behavioural changes may affect food habits during adolescence and have long-term consequences on adult health status. Also, as food habits are related to lifestyle and physical activity, all should be assessed together. This paper describes a self-administered food frequency questionnaire (FFQ) designed to assess semi-quantitatively food habits of adolescents, and evaluates its use in a study of lifestyle and physical activity. A FFQ was developed, tested in 20 adolescents and compared with a modified version of the diet history method (a combination of a 3-day dietary record and an interview with a dietitian). This validated semi-quantitative questionnaire was later included in a larger questionnaire on lifestyle and physical activity in a study of 3540 adolescents aged 9-19 years. In the validation study with 20 adolescents, the FFQ showed a good agreement with the modified version of the diet history. During the survey several consumption frequencies were found to be low. In the group of adolescents aged 14-19 years old, dairy products were consumed daily by less than 50% of the sample. About 53% girls but only 33% boys consumed one fruit daily. For one vegetable portion, these proportions were 17 and 8%, respectively. The self-administered food frequency questionnaire correctly describes food consumption in adolescents. Moreover, it was well accepted by the target group, easily understood and completed with very few problems. The results show that a significant proportion of adolescents didn>>t consume milk, fruit and vegetable on a daily basis.

En los Convenios de Ginebra del 12 de agosto de 1949 (CG), se estipula que el personal y el material sanitarios serán identificados, en general, con el emblema distintivo de la cruz roja o de la media luna roja. De conformidad con el II Convenio de Ginebra (CG II), aplicable a las víctimas de conflictos en el mar, se especifica que las superficies exteriores de los barcos hospitales y de las embarcaciones más pequeñas utilizados con fines sanitarios serán blancas. Se aboga por que las partes en conflicto utilicen «los métodos más modernos» para facilitar la identificación de los transportes sanitarios en el mar (CG II, art. 43). Se recomienda, asimismo, que las aeronaves sanitarias lleven ostensiblemente el signo distintivo, junto a los colores nacionales en las caras inferior, superior y laterales. Además, tendrán «cualquier otro sefialamiento o medio de reconocimiento concertado por los beligerantes, sea al comienzo sea en el transcurso de las hostilidades» (CG I, art. 36; CG II, art. 39).

The Geneva Conventions of 12 August 1949 provide that medical personnel and equipment shall in general be identified by the distinctive emblem of the red cross or red crescent. The Second Geneva Convention, applicable to the victims of conflict at sea, specifies that the exterior surfaces of hospital ships and smaller craft used for medical purposes shall be white and recommends that the parties to the conflict use “the most modern methods” to facilitate identification of medical transports at sea (Art. 43). It is also recommended that medical aircraft should be clearly marked with both the distinctive emblem and their national colours on their lower, upper and lateral surfaces. They should moreover be provided with “any other markings or means of identification” agreed upon between the belligerents from the outbreak or during the course of hostilities (First Convention, Art. 36, and Second Convention, Art. 39).

Los problemas que plantean las minas antipersonal, especialmente en Camboya, Afganistán, Kuwait y Angola, por solo citar los países donde hay esparcidas cantidades considerables de ellas y, además, en regiones en que representan un peligro para la población civil, incluso mucho después de terminadas las hostilidades, nos han llevado a interesarnos más de cerca por este problema.

The problems associated with the use of anti-personnel mines, especially in Cambodia, Afghanistan, Kuwait and Angola, to mention but a few of the countries where they have been deployed in large numbers and in areas where they constitute a threat to civilians long after hostilities have ceased, call for closer examination.