Impact du confort sur le choix des trajets en transport collectif

«RÉSUMÉ:Les modèles d’affectation utilisés pour la modélisation des transports collectifs permettent de déterminer le choix de trajets par les usagers en fonction de certains paramètres, tels que le temps de parcours, le nombre de correspondances, le temps d’attente et le temps d’accès. Cependant, ces modèles négligent certains paramètres, tels que la charge à bord et l’augmentation du temps de parcours par le nombre d’embarquements et de débarquements. Dans un réseau de transport collectif où la charge à bord devient élevée au point d’atteindre le point de saturation, il devient nécessaire de trouver des solutions afin de répondre convenablement aux besoins des usagers et leur offrir des options leur permettant d’accomplir leur déplacement tout en évitant une ligne chargée. Par exemple, il pourrait être pertinent d’offrir aux usagers une ligne de bus parallèle à une ligne de métro pour libérer de l’espace sur la ligne de métro. En revanche, le bus est contraint aux aléas de la circulation routière par rapport au métro, faisant qu’il peut être un choix moins attrayant pour un usager. Ainsi, il est intéressant de connaître les paramètres qui ont une influence sur le choix d’itinéraire d’un usager, dont la charge et le mode.» et «---------- ABSTRACT:The assignment models used for public transit modelling can be used to determine the route choice based on certain parameters, such as travel time, number of transfers, waiting time and access time. However, these models overlook certain parameters, such as the number of people on-board and the increase in travel time due to boarding and alighting. In a public transport network where the load approaches the point of saturation, it becomes necessary to find solutions to adequately meet the needs of users and offer them options allowing them to complete their journey while avoiding a busy line. For example, it may be appropriate to offer users a bus line parallel to a metro line to free up space on the metro line. On the other hand, the bus is constrained to road traffic compared to the metro, making it a less attractive choice for a user. Thus, it is interesting to know the parameters that influence the choice of route of a user, including the load and mode.

A defective Krab-domain zinc-finger transcription factor contributes to altered myogenesis in myotonic dystrophy type 1

Myotonic dystrophy type 1 (DM1) is an RNA-mediated disorder caused by a non-coding CTG repeat expansion that, in particular, provokes functional alteration of CUG-binding proteins. As a consequence, several genes with misregulated alternative splicing have been linked to clinical symptoms. In our search for additional molecular mechanisms that would trigger functional defects in DM1, we took advantage of mutant gene-carrying human embryonic stem cell lines to identify differentially expressed genes. Among the different genes found to be misregulated by DM1 mutation, one strongly downregulated gene encodes a transcription factor, ZNF37A. In this paper, we show that this defect in expression, which derives from a loss of RNA stability, is controlled by the RNA-binding protein, CUGBP1, and is associated with impaired myogenesis—a functional defect reminiscent of that observed in DM1. Loss of the ZNF37A protein results in changes in the expression of the subunit α1 of the receptor for the interleukin 13. This suggests that the pathological molecular mechanisms linking ZNF37A and myogenesis may involve the signaling pathway that is known to promote myoblast recruitment during development and regeneratio

The impact of COVID-19 and national pandemic responses on health service utilisation in seven low- and middle-income countries

BACKGROUND: The COVID-19 pandemic has disrupted health services worldwide, which may have led to increased mortality and secondary disease outbreaks. Disruptions vary by patient population, geographic area, and service. While many reasons have been put forward to explain disruptions, few studies have empirically investigated their causes. OBJECTIVE: We quantify disruptions to outpatient services, facility-based deliveries, and family planning in seven low- and middle-income countries during the COVID-19 pandemic and quantify relationships between disruptions and the intensity of national pandemic responses. METHODS: We leveraged routine data from 104 Partners In Health-supported facilities from January 2016 to December 2021. We first quantified COVID-19-related disruptions in each country by month using negative binomial time series models. We then modelled the relationship between disruptions and the intensity of national pandemic responses, as measured by the stringency index from the Oxford COVID-19 Government Response Tracker. RESULTS: For all the studied countries, we observed at least one month with a significant decline in outpatient visits during the COVID-19 pandemic. We also observed significant cumulative drops in outpatient visits across all months in Lesotho, Liberia, Malawi, Rwanda, and Sierra Leone. A significant cumulative decrease in facility-based deliveries was observed in Haiti, Lesotho, Mexico, and Sierra Leone. No country had significant cumulative drops in family planning visits. For a 10-unit increase in the average monthly stringency index, the proportion deviation in monthly facility outpatient visits compared to expected fell by 3.9% (95% CI: -5.1%, -1.6%). No relationship between stringency of pandemic responses and utilisation was observed for facility-based deliveries or family planning. CONCLUSIONS: Context-specific strategies show the ability of health systems to sustain essential health services during the pandemic. The link between pandemic responses and healthcare utilisation can inform purposeful strategies to ensure communities have access to care and provide lessons for promoting the utilisation of health services elsewhere

Tye7 regulates yeast Ty1 retrotransposon sense and antisense transcription in response to adenylic nucleotides stress

Transposable elements play a fundamental role in genome evolution. It is proposed that their mobility, activated under stress, induces mutations that could confer advantages to the host organism. Transcription of the Ty1 LTR-retrotransposon of Saccharomyces cerevisiae is activated in response to a severe deficiency in adenylic nucleotides. Here, we show that Ty2 and Ty3 are also stimulated under these stress conditions, revealing the simultaneous activation of three active Ty retrotransposon families. We demonstrate that Ty1 activation in response to adenylic nucleotide depletion requires the DNA-binding transcription factor Tye7. Ty1 is transcribed in both sense and antisense directions. We identify three Tye7 potential binding sites in the region of Ty1 DNA sequence where antisense transcription starts. We show that Tye7 binds to Ty1 DNA and regulates Ty1 antisense transcription. Altogether, our data suggest that, in response to adenylic nucleotide reduction, TYE7 is induced and activates Ty1 mRNA transcription, possibly by controlling Ty1 antisense transcription. We also provide the first evidence that Ty1 antisense transcription can be regulated by environmental stress conditions, pointing to a new level of control of Ty1 activity by stress, as Ty1 antisense RNAs play an important role in regulating Ty1 mobility at both the transcriptional and post-transcriptional stages

Rapid response to the M_w 4.9 earthquake of November 11, 2019 in Le Teil, Lower Rhône Valley, France

On November 11, 2019, a Mw 4.9 earthquake hit the region close to Montelimar (lower Rhône Valley, France), on the eastern margin of the Massif Central close to the external part of the Alps. Occuring in a moderate seismicity area, this earthquake is remarkable for its very shallow focal depth (between 1 and 3 km), its magnitude, and the moderate to large damages it produced in several villages. InSAR interferograms indicated a shallow rupture about 4 km long reaching the surface and the reactivation of the ancient NE-SW La Rouviere normal fault in reverse faulting in agreement with the present-day E-W compressional tectonics. The peculiarity of this earthquake together with a poor coverage of the epicentral region by permanent seismological and geodetic stations triggered the mobilisation of the French post-seismic unit and the broad French scientific community from various institutions, with the deployment of geophysical instruments (seismological and geodesic stations), geological field surveys, and field evaluation of the intensity of the earthquake. Within 7 days after the mainshock, 47 seismological stations were deployed in the epicentral area to improve the Le Teil aftershocks locations relative to the French permanent seismological network (RESIF), monitor the temporal and spatial evolution of microearthquakes close to the fault plane and temporal evolution of the seismic response of 3 damaged historical buildings, and to study suspected site effects and their influence in the distribution of seismic damage. This seismological dataset, completed by data owned by different institutions, was integrated in a homogeneous archive and distributed through FDSN web services by the RESIF data center. This dataset, together with observations of surface rupture evidences, geologic, geodetic and satellite data, will help to unravel the causes and rupture mechanism of this earthquake, and contribute to account in seismic hazard assessment for earthquakes along the major regional Cévenne fault system in a context of present-day compressional tectonics

Transitions dans le parcours de vie et construction des inégalités

Tout au long de leur existence, les individus suivent des chemins singuliers dont les trajectoires ne sont pas le simple fait de la seule volonté ou du hasard. Ces cheminements se révèlent souvent générateurs d'inégalités entre individus, notamment au cours des transitions des âges de la vie (enfance, adolescence, âge adulte, grand âge), ou lors de différentes étapes (mariage, divorce, deuil, etc). C'est afin de mieux comprendre les modalités et les combinaisons d'influence à l'origine des inégalités dans les parcours de vie, que les éditeurs de cet ouvrage ont réuni des chercheurs issus des sciences psychologiques, sociales et économiques, afin de croiser leurs regards sur la manière dont ces inégalités se creusent ou se réduisent au fil des trajectoires. Cet ouvrage interdisciplinaire met en relief la richesse d'une approche des inégalités dans la perspective dynamique du parcours de vie.Peer reviewe

Identification of a BRCA2-Specific modifier locus at 6p24 related to breast cancer risk

Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer

Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.

The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations