Oskar Bordeaux
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J Acquir Immune Defic Syndr
No full textBACKGROUND: Successful treatment of hepatitis C virus (HCV) can lead to liver fibrosis regression. It is not known who will experience fibrosis regression or how quickly it will occur. METHODS: We modelled transient elastography (TE) measurements from 1470 HIV-HCV coinfected participants followed in cohorts contributing data to InCHEHC, an international collaboration. Participants were eligible if they had at least one TE measurement in the year prior to starting a successful direct acting antiviral treatment for HCV. This measurement was used to classify participants into one of three fibrosis subgroups. We analysed measurement sequences in each subgroup using a covariate adjusted generalised additive mixed model, with an adaptive spline representing changes in the mean measurement before, during and after treatment. RESULTS: Each fibrosis subgroup had a distinctly different response. Most participants with cirrhosis (F4, TE ≥14.6 KPa) prior to HCV treatment did not show meaningful fibrosis regression - almost 70% were predicted to remain above 12 KPa three years after treatment ended. Participants with significant fibrosis (F2-F3, TE ≥7.2 and <14.6KPa) showed appreciable regression in the first two years after treatment, falling on average to levels below 7.2 KPa. Those without fibrosis prior to treatment (F0-F1) did not progress. CONCLUSION: Most coinfected people with cirrhosis prior to HCV cure will remain cirrhotic. For those with significant fibrosis, regression can be expected within two years to levels not normally associated with an increased risk of endstage liver disease. A TE measurement two years after cure should give a reliable estimate of residual fibrosis
EClinicalMedicine
Get PDFBACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are extensively evaluated for the risk of suicidal behaviors or ideation; the influence of psychiatric history or obesity on this potential effect remains to be investigated. Therefore, we aimed to assess the association between GLP-1 RA and suicide or suicide attempt, considering these factors. METHODS: Patients ≥18 y who died by suicide or were hospitalized for suicide attempt (2013-2021) with at least one GLP-1 RA dispensing within the 180 preceding days were selected from the French National Health Data System (SNDS). A case-time-control design compared, for each patient, GLP-1 RA exposure in the 30 days preceding the outcome (composite of suicide or suicide attempt) to three earlier 30-day reference periods. Potential exposure trend bias was controlled using up to five time-controls matched on age, sex, psychiatric history, obesity, calendar time. Analyses were adjusted for time-varying confounders. Finally dipeptidyl peptidase-4 (DPP-4) inhibitors were studied as negative controls for potential biases. FINDINGS: This study included 1102 cases and 5494 controls. Mean case age was 57.4 years (SD 11.4); 44.6% were male, 67.6% had a recent psychiatric history and 51.3% had obesity. GLP-1 RA use was not associated with an increased risk of suicide or suicide attempt (OR, 0.62; 95% CI, 0.51-0.75), with consistent results for DPP-4 inhibitors (0.75; 0.67-0.84). Results obtained according to recent psychiatric history and obesity were comparable. INTERPRETATION: This large nationwide case-time-control study provides reassurance about the short-term psychiatric safety of GLP-1 RA, showing no specific risk for patients with psychiatric disorders or obesity. FUNDING: French Medicines Agency
Phases of Magmatism and Tectonics Along the Madagascar‐Comoros Volcanic Chain, and Synchronous Changes in the Kinematics of the Lwandle and Somalia Plates
Get PDFThis paper aims to solve the longstanding debate on the origin of the Comoros volcanic archipelago (Mozambique Channel, Indian Ocean) concerning whether it represents a hotspot trail or a boundary between the Lwandle and Somalia plates in possible connection with the East African Rift System (EARS). To achieve this goal, we analyzed rock samples from recently discovered and previously uninvestigated volcanoes and edifices by means of geochemistry and geochronology. Major-trace element analyses and radiometric dating (40Ar/39Ar, K-Ar, and (U-Th)/He) allow us to identify a widespread phase of Comorian volcanism initiated at 9–8 Ma, involving the Zélée, Geyser, and Leven banks, three atolls east of the Comoros. Another tectono-magmatic phase initiated at 2.5 Ma led to a N-S widening of seamount volcanism, and to the progressive development of en-échelon NW-SE structures. With this new addition of atolls and seamounts, the Comoros Archipelago becomes a ∼700 km-long, ∼200 km-wide E-W chain extending from the Cenozoic volcanoes of Madagascar to the EARS. The reactivation of this chain at 9–8 and 2.5 Ma coincides with abrupt changes in the motion of the Somalia plate relative to the Lwandle plate, and with plate boundary modifications. The en-échelon reorganization of structures also matches the kinematic evolution of Somalia relative to Lwandle, from transtension (>3 Ma) to pure dextral slip (≤3 Ma) in the northern Mozambique Channel. We conclude that the Madagascar-Comoros volcanic chain is a branch of the EARS and a plate boundary, further strengthening the link between magmatism and the Rovuma-Lwandle-Somalia plate kinematics.COmores & maYotte : vOlcanisme, TEctonique et Sismicit
Charter for access to IN-SYLVA France Services
No full textLa présente charte est destinée à toute personne souhaitant porter un projet qui sollicite des Services de l’Infrastructure de Recherche (IR) IN-SYLVA France et en présente les modalités de sollicitation. Les bonnes pratiques proposées dans cette charte permettent à IN-SYLVA France de bien accueillir les projets et de les accompagner.This charter is intended for anyone wishing to carry out a project that requests Services from the Research Infrastructure (RI) IN-SYLVA France. It sets out the terms and conditions of such request. The best practices proposed in this charter will enable IN-SYLVA France to welcome and support projects
Sci Adv
Get PDFBacterial type IV secretion systems (T4SSs) are widespread nanomachines specialized in the transport across the cell envelope of various types of molecules including mobile genetic elements during conjugation. Despite their prevalence in Gram-positive bacteria, including relevant pathogens, their assembly and functioning remain unknown. This study addresses these gaps by investigating VirB8 proteins, known to be central components of conjugative T4SSs in Gram-positive bacteria. However, the functional packing and precise role of VirB8 in T4SSs biology remain undefined. Our findings elucidate the nature of VirB8 proteins as cell wall components, where they multimerize and exhibit a conserved assembly pattern, distinct from VirB8 in Gram-negative bacteria. We also demonstrate that VirB8 proteins interact with other T4SS subunits and DNA, indicating their pivotal role in the building of the DNA translocation channel across the cell wall. We lastly propose a distinct architecture for conjugative T4SSs in Gram-positive bacteria compared to their Gram-negative counterparts, possibly attributed to the differences in the cell wall structure
Comparación de las características fisicoquímicas de la cerámica producida por Chupícuaro y Cuicuilco
No full textRéinterpréter les interactions Chupicuaro - Cuicuilco à la lumière des technologies céramiques (période préclassique, Mésoamérique).El objetivo de esta presentación es esclarecer la naturaleza e intensidad de las relaciones entre dos focos culturales, Chupícuaro en el Valle de Lerma (Guanajuato) y Cuicuilco en la Cuenca de México, entre los años 600 a.C. y 250 d.C. Se realizó un estudio arqueométrico de un corpus de más de 200 tiestos cerámicos de la cultura Chupícuaro (TR.6 y JR.24), así como de 25 tiestos de los sitios Cuicuilco y Cerro del Tepalcate. Las pastas y decoraciones fueron analizadas mediante diversas técnicas analíticas (SEM-EDS, pXRF, etc.). La comparación de los productos revela una serie de similitudes, lo que sugiere que es necesario seguir trabajando en un corpus más amplio
Mapler: Assessing assembly quality in taxonomically-rich metagenomes sequenced with HiFi reads
No full textEvaluating the quality of metagenome assemblies can be a challenging task, especially when no reference genome is available and when comparing samples at various taxonomic complexity and sequencing depth. A high quality assembly is expected not only to produce high quality bins, but also to be representative of most of the read sequences, especially in complex samples where algorithms struggle reconstructing low-abundance genomes. Recent studies showed a great improvement in number and quality of bins obtained with highly accurate PacBio HiFi long reads. It remains however to be assessed how much of the sample these bins represent, especially in highly complex environmental samples. There is therefore a need to use and compare other evaluation methods. We designed and implemented Mapler, a metagenomic assembly and evaluation pipeline with a primary focus on evaluating the quality of HiFi-based metagenome assemblies. It incorporates state-of-the-art tools for assembly, binning, and assembly evaluation. In addition to classifying assembly bins in classical quality categories according to their marker gene content and taxonomic assignment, Mapler analyzes the alignment of reads on contigs. To do so, it calculates the ratio of mapped reads and bases, and separately analyzes mapped and unmapped reads via their k-mer frequency, read quality, and taxonomic assignment.Computationel models of crop plant microbial biodiversit
J Thromb Haemost
No full textBackground: The long-term recurrence risk after a pregnancy-associated venous thromboembolism (VTE) is sparsely assessed. Objectives: To determine the rate of recurrence after a pregnancy-associated VTE and identify associated risk factors. Methods: Five hundred eighty-seven women with a history of first VTE occurring during pregnancy or up to 3 months after delivery were referred to La Timone Hospital, Marseille, France. Women were consecutively included between 2000 and 2015. VTE characteristics and biological parameters were collected upon inclusion. During the 2016-2019 period, patients were recontacted to gather information on postinclusion VTE. A weighted Cox model, adapted to the study's ambispective design, was used to analyze pre- and postinclusion VTE recurrences. Results: After quality controls, 583 women were analyzed. The incidence of recurrent VTE was 2.4% person-years. The cumulative risk of VTE recurrence was 38% (n = 221), with a median follow-up of 31 years (95% CI: 27-35); 6%, 13%, 17%, and 30% at 2, 5, 10, and 30 years respectively. Pulmonary embolism at first event was associated with a 2-fold increased risk of pulmonary embolism at recurrence compared with isolated deep venous thrombosis (DVT, hazard ratio [HR]: 2.63; 95% CI: 1.44-4.82). Risk factors significantly associated with recurrence were interrupted pregnancies (HR: 1.85; 95% CI: 1.18-2.90), lower limb DVT (HR: 2.95; 95% CI: 1.16-7.49), and AB blood group (HR: 1.71; 95% CI: 1.06-2.77). Conclusion: Although the recurrence risk is low within the first 10 years after a pregnancy-associated VTE, one-third of patients experienced a new event over a 30-year period. Interrupted pregnancies, lower limb DVT, and AB blood group were associated with higher risk of recurrence
Immunotherapy
Get PDFWhat is this summary about?This is a summary of the results of 2 clinical studies , called OAKS and DERBY, that tested a medicine called pegcetacoplan. Pegcetacoplan is the first United States Food and Drug Administration (US FDA) approved treatment for geographic atrophy, commonly referred to as GA, a common eye disease in older people. Geographic atrophy is a form of late age-related macular degeneration, or AMD, that usually starts after age 50. The US FDA approved pegcetacoplan based on the results from these 2 clinical studies. Pegcetacoplan is covered by Medicare and most insurance companies in the United States.What are the key takeaways?The results of the OAKS and DERBY clinical studies show that treatment with pegcetacoplan led to slower growth of GA lesions in the retina. The retina is the light-sensitive tissue at the back of the eye. In other words, it slowed the growth of the areas where cells were dying. When compared to a sham procedure, pegcetacoplan injection slowed the growth of lesions by 19% to 22% (when given every 4 weeks) and 16% to 18% (when given every 8 weeks) in OAKS and DERBY, respectively.After 2 years of treatment, there were no differences in the average vision function between participants treated with pegcetacoplan and participants who received a sham procedure.The most common eye-related health issues reported were like those reported with all types of intravitreal injections and most were temporary.What were the main conclusions reported by the researchers?Based on the results of these 2 large clinical studies, pegcetacoplan slows GA disease progression with an incidence of eye-related health issues similar to other drugs given by intravitreal injection.[Box: see text]. en