The European Migration System and Global Justice. A First Appraisal

Migration is at the heart of the current political debate in Europe. Moreover, the migration crisis has disclosed a number of normative and ethical issues connected to the current management of migration in the EU. This report provides a preliminary insight into the EU’s policy on migration. It looks specifically at the terms the EU chooses, the definitions it devises and the concepts and understandings it endorses in its migration policies. In order to grasp the actual working of an emerging EU Migration System of Governance (EUMSG), the same terms, concepts and definitions are also examined with reference to a set of national cases: Italy, France, Germany, United Kingdom, Hungary, Greece and Norway

Application du système de scoring lésionnel pour contribuer à l’étude de la pathogénicité du virus de l’influenza aviaire faiblement pathogène H9N2 chez le poulet de chair infecté expérimentalement

Following the introduction of the low pathogenic avian influenza virus H9N2 in Morocco in 2016, a study of the pathogenicity of the virus was carried out, to fully understand the pathophysiology of the disease and its role in the damage observed in the field. . The study was carried out under controlled conditions so that the true impact of the H9N2 virus alone could be demonstrated by limiting concomitant infections. To do this, 110 day-old broilers vaccinated to one day of age against the low pathogenic avian influenza virus H9N2 were reared and maintained in isolators. At 21 days, the chicks were divided into three batches, two batches (vC, nvC) were inoculated with the Moroccan strain of the H9N2 virus (GenBank accession number: LT 598532) and an uncontested control batch (vNC). The results of clinical examinations revealed only respiratory discomfort and no mortality. Two autopsies were scheduled for 5 and 12 days post-challenge. Lesionally, tracheitis, thickening of the air sacs, and pulmonary congestion were observed during the first autopsy, during the second, only the thickening of the air sacs persisted. The histopathological study carried out on the organs removed during the autopsies, revealed lymphohistiocytic tracheitis, severe bronchitis, mild lymphocytic nephritis and lymphocyte depletion in the spleen at 5 days post challenge, 12 days post-challenge , the lesions regressed and only a few cases of tracheitis were detected. The present study is the first to have investigated the pathogenic effect of the virus alone under controlled conditions, the results indicate that infection with the virus alone does not reproduce the disease as reported in the field and that of other factors (concomitant infections, breeding conditions and environmental stress, etc.) may be at the origin of the seriousness of the damage reported, the team also concluded that the Moroccan strain of the H9N2 AI virus has an essentially respiratory tropism and a weak nephropathogenic effect. Keywords: Avian influenza, experimental infection, broiler chickens, H9N2, histopathologySuite à l’introduction du virus de l’influenza aviaire faiblement pathogène H9N2 au Maroc en 2016, une étude de la pathogénicité du virus a été effectuée, pour bien comprendre la pathophysiologie de la maladie et son rôle dans les dégâts observés au niveau du terrain. L’étude a été effectuée dans des conditions contrôlées pour pouvoir ressortir le véritable impact du virus H9N2  seul en limitant les infections concomitantes. Pour ce faire, 110 poulets de chair d’un jour vaccinés à un jour d’âge,  contre le virus de l’influenza aviaire faiblement pathogène H9N2, ont été élevés et entretenus dans des isolateurs. A 21 jours, les poussins ont été répartis en trois lots,  deux  lots (vC, nvC) ont été inoculé par la souche marocaine du virus H9N2 (GenBank  accession number : LT 598532)  et un lot témoin non challengé (vNC). Les résultats des examens cliniques ont révélé une gêne respiratoire seulement et  aucune mortalité. Deux autopsies ont été programmées à 5 et à 12 jours post-challenge. Sur le plan lésionnel, une trachéite, un épaississement des sacs aériens, et une congestion pulmonaire ont été observés pendant la première autopsie, lors de la deuxième, seulement l’épaississement des sacs aériens a persisté. L’étude histopathologique réalisée sur les organes prélevés lors des autopsies, a révélé une trachéite lympho-histiocytaire, une bronchite sévère, une néphrite lymphocytaire légère  et une déplétion lymphocytaire au niveau de la rate à 5 jours post challenge, à 12 jours post-challenge, les lésions ont régressé et seulement quelques cas de trachéite ont été détectés. La présente étude est la première à avoir étudié l’effet pathogène du virus seul dans des conditions contrôlées, les résultats  indiquent que l’infection par le virus seul ne reproduit pas la maladie telle qu’elle est rapportée dans le terrain et que d’autres facteurs (infections concomitantes, conditions d’élevage et stress environnemental…) peuvent être à l’origine de la gravité des dégâts rapportés,  l’équipe a aussi conclu que  la souche marocaine du virus de l’IA  H9N2  a un tropisme essentiellement  respiratoire et un effet néphropathogène faible. Mots-clés : Influenza aviaire, infection expérimentale, poulet de chair, H9N2, histopathologie   &nbsp

Semi-quantitative scoring system for the evaluation of microscopic lesions in the trachea of turkeys following experimental infection with LPAI H9N2

Dans le cadre de l’étude de la pathogénicité et de l’évaluation de la vaccination du virus de l’Influenza Aviaire faiblement pathogène H9N2 chez la dinde ; une étude histopathologique des lésions engendrées par ce virus suite à l’infection expérimentale de la dinde a été réalisée.  Ainsi, 80 dindonneaux ont été mis en essai, et vaccinés contre H9N2 à 8 jours d’âge et le challenge à 26 jours. Un monitoring clinique a été effectué après le challenge, avec la réalisation de deux autopsies à 5 jours et à 10 jours post-challenge. Les dindonneaux ont manifesté des signes respiratoires avec des râles trachéaux, la toux, une sinusite avec des écoulements nasaux et oculaires mousseux, associés à des symptômes généralisés y compris l’entassement, la léthargie et un plumage ébouriffé. Des taux de mortalité de 50 et 20% ont été relevés respectivement chez le groupe de dindonneaux non vaccinés et vaccinés. Sur le plan lésionnel, une sinusite fibrineuse, une trachéite, et une aérosacculite fibrineuse ont été notés chez les deux groupes challengés, à moindre degré chez les vaccinés, avec une pneumonie fibrineuse détectée seulement chez les non vaccinés. L’étude histpathologique a révélé des lésions similaires à la fois chez les groupes vaccinés et non vaccinés à 5 et à 10 jours post-challenge, qui ne différent que par leur gravité. Ainsi un système de scoring de 4 grades (de 0 à 3) a été adopté pour évaluer les lésions trachéales chez les lots d’oiseaux étudiés, la comparaison de ceux-ci s’est basée principalement, sur l’évolution des grades et la précocité de retour à la normale (grade 0). Les lésions ont été plus sévères pendant l’autopsie de 5 JPC, une différence entre les groupes a été relevée, mais aucune différence statistique n’a été démontrée. En conclusion, le système de scoring procure des résultats cohérents ce qui prouve sa fiabilité en tant qu’outil supplémentaire dans les études expérimentales en pathologie aviaire.  Mots-clés: Lésions Histopathologiques, scoring lésionnel, dinde, H9N2, infection expérimentaleThe present study has been designed to contribute both in the evaluation of the pathogenicity of the Moroccan strain of low pathogenic avian influenza virus (LPAI) H9N2 in turkeys and vaccine efficacy against it. For this purpose, clinical monitoring and examination of gross and hitopathological lesions following vaccination at 8 days and a challenge at 26 days of age were carried out. The study was conducted on 80 turkeys, which were divided into 4 groups (A: vaccinated and challenged, B: vaccinated and unchallenged, C: unvaccinated and challenged, and D: unvaccinated and unchallenged). Birds were observed daily for 15 days after the challenge for clinical signs. 10 poults from each group were euthanized and autopsied 5 days post-challenge (DPC) and at 10 DPC. Gross lesions were evaluated during necropsy, and trachea samples were collected, and placed in a 10% neutral buffered formalin solution for histopathological examination. All challenged birds exhibited respiratory signs during the observation period which consisted of rales, coughing, sinusitis and ocular and nasal discharges, with lethargy and ruffled feathers. Mortalities of 20 % and 50 % starting 7 DPC were recorded in group A and B respectively. Necropsy revealed fibrinous sinusitis, tracheitis, and fibrinous aerosacculitis in groups A and B with pneumonia only in group B at 5 DPC.  Histopathology of the trachea in all the infected birds revealed a lympho-plasmocytic tracheitis with mononuclear cell infiltrates, hyperplasia of epithelial cells, metaplasia, and loss of cilia and mucous glands. Lesions exhibited a varying range of severity depending on days post challenge and groups. Thus a scoring system of 4 grades was created to evaluate and compare groups. Score 0 corresponds to normal tracheal structure, histologic scores of 1 and 2 are characterized mainly by congested blood vessels, depletion of specialized cells, and mononuclear infiltrates, while score 3 corresponds to a histologic pattern of notable thickening of mucosal lining by hyperplasia of epithelial cells, severely congested blood vessels, and metaplasia of surface epithelial cells. Lesions were significantly more severe at 5 DPC, and a visual but non-statistical difference between groups at the same necropsy was noted. The scoring system showed consistent results and helped broaden the perspectives of the present study, and proved to be a reliable tool in the setting of experimental studies in avian pathology.  Keywords: Histopathologic lesions, scoring system, Turkey, H9N2, experimental infectio

Oxidation state dependent conformational changes of HMGB1 regulate the formation of the CXCL12/HMGB1 heterocomplex

High-mobility Group Box 1 (HMGB1) is an abundant protein present in all mammalian cells and involved in several processes. During inflammation or tissue damage, HMGB1 is released in the extracellular space and, depending on its redox state, can form a heterocomplex with CXCL12. The heterocomplex acts exclusively via the chemokine receptor CXCR4 enhancing leukocyte recruitment. Here, we used multi-microsecond molecular dynamics (MD) simulations to elucidate the effect of the disulfide bond on the structure and dynamics of HMGB1. The results of the MD simulations show that the presence or lack of the disulfide bond between Cys23 and Cys45 modulates the conformational space explored by HMGB1, making the reduced protein more suitable to form a complex with CXCL12

CTCF variants in 39 individuals with a variable neurodevelopmental disorder broaden the mutational and clinical spectrum

Purpose: Pathogenic variants in the chromatin organizer CTCF were previously reported in seven individuals with a neurodevelopmental disorder (NDD). Methods: Through international collaboration we collected data from 39 subjects with variants in CTCF. We performed transcriptome analysis on RNA from blood samples and utilized Drosophila melanogaster to investigate the impact of Ctcf dosage alteration on nervous system development and function. Results: The individuals in our cohort carried 2 deletions, 8 likely gene-disruptive, 2 splice-site, and 20 different missense variants, most of them de novo. Two cases were familial. The associated phenotype was of variable severity extending from mild developmental delay or normal IQ to severe intellectual disability. Feeding difficulties and behavioral abnormalities were common, and variable other findings including growth restriction and cardiac defects were observed. RNA-sequencing in five individuals identified 3828 deregulated genes enriched for known NDD genes and biological processes such as transcriptional regulation. Ctcf dosage alteration in Drosophila resulted in impaired gross neurological functioning and learning and memory deficits. Conclusion: We significantly broaden the mutational and clinical spectrum of CTCF-associated NDDs. Our data shed light onto the functional role of CTCF by identifying deregulated genes and show that Ctcf alterations result in nervous system defects in Drosophila.Peer reviewe

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020