Etude de cas portant sur la révision du dispositif d'évaluation des enseignements à l'Université de Liège

La littérature francophone dans le domaine de l’évaluation des enseignements (EE) comprend un certain nombre d’études de cas portant sur la mise en route d’un dispositif EE. Elle nous présente par ailleurs de nombreux dispositifs d’EE riches et variés. Par contre, elle est plus silencieuse sur les éléments en tension lors de réformes de dispositifs EE préexistants. Peut-on en déduire que la mise en place d’un système d’EE et sa refonte obéissent aux mêmes logiques. Cela ne nous semble pas être le cas. Les résistances à l’évaluation nous semblent prendre une forme différente dans les deux cas de figure envisagés : par exemple, nous avons constaté que lors d’une reforme du dispositif, ce n’est plus l’idée et la pertinence même de l’évaluation qui est sujette à caution, mais bien le rapport coût bénéfice pour chacun des acteurs concernés. Cet exemple illustre l’intérêt de décrire, sous la forme d’études de cas, des situations de réformes avec leurs freins et adjuvants spécifiques. C’est l’objectif de notre contribution qui décrit la refonte du système d’EE à l’Université de Liège. Au final, la procédure aujourd’hui proposée nous semble riche et complète. En effet, elle distingue 4 acteurs de la régulation des enseignements auxquels elle propose 6 outils de récolte de données. Ce dispositif nous semble par ailleurs répondre à un certain nombre de prescrits ou de conseils présents dans la littérature que nous développerons lors de notre présentation

Breast cancer stem cells with tumor- versus metastasis-initiating capacities are modulated by TGFBR1 inhibition

Cancer stem cells (CSCs) are defined by their ability to regenerate a tumor upon transplantation. However, it is not yet clear whether tumors contain a single CSC population or different subsets of cells with mixed capacities for initiating primary and secondary tumors. Using two different identification strategies, we studied the overlap between metastatic stem cells and tumor-initiating cells (TICs) in the MMTV-PyMT model. Our results show that in the MMTV-PyMT model, Lin−CD90−ALDHhigh cells retained a high tumor-initiating potential (TIP) in orthotopic transplants, in contrast to Lin−CD24+CD90+, which retained higher metastatic capacity. Interestingly, suppression of TGFβ signaling increased TIC numbers. We here describe the existence of distinct populations of CSCs with differing capacities to initiate tumors in the primary or the secondary site. Inhibiting TGFβ signaling shifts the balance toward the former, which may have unanticipated implications for the therapeutic use of TGFβ/TGFBR1 inhibitors

The Amyotrophic Lateral Sclerosis M114T PFN1 Mutation Deregulates Alternative Autophagy Pathways and Mitochondrial Homeostasis

International audienceMutations in profilin 1 (PFN1) have been identified in rare familial cases of Amyotrophic Lateral Sclerosis (ALS). PFN1 is involved in multiple pathways that could intervene in ALS pathology. However, the specific pathogenic role of PFN1 mutations in ALS is still not fully understood. We hypothesized that PFN1 could play a role in regulating autophagy pathways and that PFN1 mutations could disrupt this function. We used patient cells (lymphoblasts) or tissue (post-mortem) carrying PFN1 mutations (M114T and E117G), and designed experimental models expressing wild-type or mutant PFN1 (cell lines and novel PFN1 mice established by lentiviral transgenesis) to study the effects of PFN1 mutations on autophagic pathway markers. We observed no accumulation of PFN1 in the spinal cord of one E117G mutation carrier. Moreover, in patient lymphoblasts and transfected cell lines, the M114T mutant PFN1 protein was unstable and deregulated the RAB9-mediated alternative autophagy pathway involved in the clearance of damaged mitochondria. In vivo, motor neurons expressing M114T mutant PFN1 showed mitochondrial abnormalities. Our results demonstrate that the M114T PFN1 mutation is more deleterious than the E117G variant in patient cells and experimental models and suggest a role for the RAB9-dependent autophagic pathway in ALS

GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits

Obesity promotes the expansion of metastasis-initiating cells in breast cancer

Obesity is a strong predictor of poor prognosis in breast cancer, especially in postmenopausal women. In particular, tumors in obese patients tend to seed more distant metastases, although the biology behind this observation remains poorly understood.Methods: To elucidate the effects of the obese microenvironment on metastatic spread, we ovariectomized C57BL/6 J female mice and fed them either a regular diet (RD) or a high-fat diet (HFD) to generate a postmenopausal diet-induced obesity model. We then studied tumor progression to metastasis of Py230 and EO771 grafts. We analyzed and phenotyped the RD and HFD tumors and the surrounding adipose tissue by flow cytometry, qPCR, immunohistochemistry (IHC) and western blot. The influence of the microenvironment on tumor cells was assessed by performing cross-transplantation of RD and HFD tumor cells into other RD and HFD mice. The results were analyzed using the unpaired Student t test when comparing two variables, otherwise we used one-way or two-way analysis of variance. The relationship between two variables was calculated using correlation coefficients.Results: Our results show that tumors in obese mice grow faster, are also less vascularized, more hypoxic, of higher grade and enriched in CD11b+Ly6G+ neutrophils. Collectively, this favors induction of the epithelial-to-mesenchymal transition and progression to claudin-low breast cancer, a subtype of triple-negative breast cancer that is enriched in cancer stem cells. Interestingly, transplanting HFD- derived tumor cells in RD mice transfers enhanced tumor growth and lung metastasis formation.Conclusions: These data indicate that a pro-metastatic effect of obesity is acquired by the tumor cells in the primary tumor independently of the microenvironment of the secondary site

Long-term cellular immunity of vaccines for Zaire Ebola Virus Diseases

Recent Ebola outbreaks underscore the importance of continuous prevention and disease control efforts. Authorized vaccines include Merck’s Ervebo (rVSV-ZEBOV) and Johnson & Johnson’s two-dose combination (Ad26.ZEBOV/MVA-BN-Filo). Here, in a five-year follow-up of the PREVAC randomized trial (NCT02876328), we report the results of the immunology ancillary study of the trial. The primary endpoint is to evaluate long-term memory T-cell responses induced by three vaccine regimens: Ad26–MVA, rVSV, and rVSV–booster. Polyfunctional EBOV-specific CD4+ T-cell responses increase after Ad26 priming and are further boosted by MVA, whereas minimal responses are observed in the rVSV groups, declining after one year. In-vitro expansion for eight days show sustained EBOV-specific T-cell responses for up to 60 months post-prime vaccination with both Ad26-MVA and rVSV, with no decline. Cytokine production analysis identify shared biomarkers between the Ad26-MVA and rVSV groups. In secondary endpoint, we observed an elevation of pro-inflammatory cytokines at Day 7 in the rVSV group. Finally, we establish a correlation between EBOV-specific T-cell responses and anti-EBOV IgG responses. Our findings can guide booster vaccination recommendations and help identify populations likely to benefit from revaccination

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

"Dissenting at the United Nations: Interaction orders and Venezuelan contestation practices (2015–16)"

International audienceThe Venezuelan participation in the United Nations Security Council (UNSC) in 2015 and 2016 was expected to be a challenge for the institution, as the Maduro government adopted controversial positions at the General Assembly (UNGA). However, Venezuela contestation line did not appear clearly at the UNSC. Drawing upon an in-depth qualitative study, Erving Goffman's work, and literature on contestation in international organisations (IOs), we interpret this apparent inconsistency from the concept of interaction order. We argue that the UNGA and the UNSC each constitutes a specific interaction order that influences the way contestation practices are channelled. The contestation practices Venezuelan representatives set up at the UNGA hardly work during the UNSC official sessions, where they adapt their practices to its interaction order. Venezuelan representatives also use informal and backstage actions to express their dissent, without avoiding being called into order. Venezuela's moderation at the UNSC results from an invisibilisation of contestation by interaction practices