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The objective of the GeoCarbone-Injectivity project was to develop a methodology to study the complex phenomena involved in the near wellbore region during CO2 injection. This paper presents an overview of the program and results of the project, and some further necessary developments. The proposed methodology is based on experiments and simulations at the core scale, in order to understand (physical modelling and definition of constitutive laws) and quantify (calibration of simulation tools) the mechanisms involved in injectivity variations: fluid/rock interactions, transport mechanisms, geomechanical effects. These mechanisms and the associated parameters have then to be integrated in the models at the wellbore scale. The methodology has been applied for the study of a potential injection of CO2 in the Dogger geological formation of the Paris Basin, in collaboration with the other ANR GeoCarbone projects. L’objectif du projet GéoCarbone-Injectivité était de définir une méthodologie pour étudier les phénomènes complexes intervenant aux abords des puits lors de l’injection de CO2. La méthodologie proposée s’appuie sur des expérimentations interprétées numériquement à l’échelle de la carotte afin de comprendre (modélisation physique et lois de comportement) et de quantifier (paramétrisation des outils de simulation) les différents mécanismes susceptibles de modifier l’injectivité : les interactions roche/fluide, les mécanismes de transport aux abords du puits d’injection et les effets géomécaniques. Ces mécanismes et les paramètres associés devront ensuite être intégrés dans une modélisation à l’échelle métrique à décamétrique des abords du puits d’injection. Cette approche a été appliquée pour l’étude d’une injection potentielle de CO2 dans la formation géologique du Dogger du Bassin Parisien, en relation avec les projets ANR GéoCarbone.

Abstract: To ensure safe behavior during the whole lifetime of the geological storage of CO2, site selection and its characterization are essential corner stones. This paper presents the different milestones and the results of each step of the site characterization implemented on a potential storage site in the Triassic deep saline aquifer of the Paris Basin. It addresses a well known theory and practical aspects and challenges of the first phase of real site identification carried out by Veolia Environnement and Geogreen. The initial static and dynamic characterization of the storage complex will mainly rely on available public or proprietary data. Different challenges related to the gathering and validation of existing data are discussed. The characterization methodology should aim at re-interpreting the available data in order to populate a dynamic model at semi-regional scale of the storage complex. 2D Seismic data reprocessing made it possible to determine the local structure of the storage. Regional structural information must also been considered since industrial scale injection impacts a significant area with respect to overpressure extension. To complete the storage complex description, upper laying structures and aquifers must be adequately described up to the ground level. When elaborating such a 3D model, data consistency at the different scales should be carefully checked. Facies variations, porosity and both vertical and horizontal permeabilities will control storage capacity and well injectivity. Thus, an extensive log analysis is a major step in the characterization methodology. When available, core samples and flow tests must also be reconsidered to enhance the model quality. Furthermore, petrophysical interpretation of logs will improve site characterization and enable mineral trapping assessment. The consistent re-interpretation of available well logs will ensure proper site characterization in terms of reservoir and containment. Some examples are provided to illustrate the relevance of re-interpretation work. Building a 3-D geological model is a major integrating step of the available dataset on the area of interest both in terms of structure and heterogeneities at different scales (facies, mineral, petrophysical …). At this stage, the different assumptions should be carefully revisited in light of the available data. The geological uncertainties can then be estimated using a statistical approach, which highlights key petrophysical characteristics of the storage along with main risks that need to be assessed. The final step in the characterization methodology includes a dynamic assessment of the short term effects on injectivity and capacity, and of long term trapping mechanism. On the short term, potential interference with other sub-surface activities needs to be investigated along with the potential migration pathways (existing wells and faults). Models were elaborated at different scales. A near-wellbore model helped to estimate chemical induced effects. A storage site model helped to estimate overpressure and CO2 plume behaviors, and a model larger than the storage complex helped to identify migration pathways and constraint boundary conditions. Different assumptions and operational constraints were supposed to ensure the robustness of different injection scenarios. The results of corresponding dynamic simulations are presented and discussed. [Copyright &y& Elsevier]

Abstract: The METSTOR project offers a methodology to look for potentially interesting CO2 storage areas in France at the initial stage, before the “site selection” step. Our tool, embodied in a Geographic Information System, is based on an interactive map of CO2 storage capacities. Other relevant information layers are included. The geographic layers are complemented with a series of online technical notices. It seems to be the first open online GIS that offers policy makers, businesses and the public at large an integrated access to that necessary information. Our prototype, limited mainly to the Paris Basin, is released online at www.metstor.fr. [Copyright &y& Elsevier]

To combat the COVID-19 pandemic, many European countries have developed a public health strategy involving the use of digital contact tracing (DCT) applications to improve timely tracking and contact tracing of COVID-19 cases. France's independent COVID-19 Control and Society Connection Council (CCL) was established by law in May 2020 to issue advice and recommendations on the national epidemic digital systems. In this paper, we present the recommendations by the CCL, with the objective to increase the uptake and utility of French DCT applications. As the country's most vulnerable population has been subjected to greater virus exposure, a stronger impact of the lockdown, and less access to preventive and health care services, the CCL is particularly aware of health inequalities. The French DCT app TousAntiCovid had been downloaded by 13.6 million users (ie, 20% of the French population) in March 2021. To promote the use of DCT apps, the CCL has recommended that communication about the app's individual and collective objectives be increased. The CCL has also recommended the introduction of clear, simple, accessible, incentivizing, noncoercive information within the digital tools. In addition, the CCL has recommended improving public health policies to address the needs of the underprivileged. The CCL calls for promoting population empowerment with the use of digital tools, improving public health culture for decision-makers dealing with health determinants, taking social considerations into account, and incorporating community participation., (©Marion Albouy-Llaty, Caroline Martin, Daniel Benamouzig, Eric Bothorel, Gilles Munier, Catherine Simonin, Jean-Louis Guéant, Emmanuel Rusch. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 07.10.2021.)

Recent studies have suggested including nonstructural proteins as Tat and Vpr in HIV vaccines. However, little is known about the CD4+ T-cell response that these small proteins induce in humans. We have therefore evaluated these responses by in vitro priming experiments of CD4+ T lymphocytes harvested in healthy donors. In the Tat protein, only one peptide primed CD4+ T cells of eight HLA unrelated healthy donors. T cells induced by this peptide recognized immature DC loaded with the native Tat protein and are restricted by multiple HLA-DR molecules, in agreement with its binding capacity. This peptide was therefore processed in an appropriate manner and was highly immunoprevalent. CD4+ T-cell response to Vpr peptides was more disperse and involved six different peptides depending on the HLA-DR molecules of the donors. Two overlapping peptides were T-cell stimulating in at least half of the donors. T-cell response to Vpr in multiple donors is the result of a combination of several CD4+ T-cell epitopes with good to moderate immunoprevalence. Altogether, our results show that the frequency of responders to HIV Tat or Vpr proteins relies on one or multiple CD4+ T-cell epitopes, respectively.

Because of the wide distribution of the survivin Ag in a variety of tumors, we have investigated the survivin-specific CD4+ T cell response in healthy donors and cancer patients. Screening of the entire sequence of survivin for HLA class II binding led to the identification of seven HLA-DR promiscuous peptides, including four HLA-DP4 peptides. All of the peptides were able to prime in vitro CD4+ T cells of eight different healthy donors. The peptide-specific T cell lines were stimulated by dendritic cells loaded with the recombinant protein or with the lysates of tumor cells. The high frequency of responders (i.e., immunoprevalence) was provided by a wide reactivity of multiple peptides. Six peptides were T cell stimulating in at least half of the donors and were close to CD8+ T cell epitopes. HLA-DR molecules were more frequently involved in T cell stimulation than were HLA-DP4 molecules, and hence immunoprevalence relies mainly on HLA-DR promiscuity in the survivin Ag. In two cancer patients a spontaneous CD4+ T cell response specific for one of these peptides was also observed. Based on these observations, the tumor-shared survivin does not appear to be the target of immune tolerance in healthy donors and cancer patients and is a relevant candidate for cancer vaccine.

The Phoenix automated microbiology system (BD Diagnostics, Sparks, MD) is designed for the rapid identification (ID) and antimicrobial susceptibility testing (AST) of clinically significant human bacterial pathogens. We evaluated the performance of the Phoenix instrument in comparison with that of the MicroScan WalkAway system (Dade Behring, West Sacramento, CA) in the ID and AST of gram-negative clinical strains and challenge isolates of Enterobacteriaceae (n = 150) and nonfermentative gram-negative bacilli (NFGNB; 45 clinical isolates and 8 challenge isolates). ID discrepancies were resolved with the API 20E and API 20NE conventional biochemical ID systems (bioMerieux, Durham, NC). The standard disk diffusion method was used to resolve discordant AST results. The overall percentages of agreement between the Phoenix ID results and the MicroScan results at the genus and species levels for clinical isolates of Enterobacteriaceae were 98.7 and 97.7%, respectively; following resolution with conventional biochemical testing, the accuracy of the Phoenix system was determined to be 100%. For NFGNB, the levels of agreement were 100 and 97.7%, respectively. Both systems incorrectly identified the majority of the uncommon nonfermentative nonpseudomonal challenge isolates recovered from cystic fibrosis patients; these isolates are not included in the databases of the respective systems. For AST of Enterobacteriaceae, the rate of complete agreement between the Phoenix results and the MicroScan results was 97%; the rates of very major, major, and minor errors were 0.3, 0.2, and 2.7%, respectively. For NFGNB, the rate of complete agreement between the Phoenix results and the MicroScan results was 89.1%; the rates of very major, major, and minor errors were 0, 0.5, and 7.7%, respectively. Following the confirmatory testing of nine clinical isolates initially screened by the MicroScan system as possible extended-spectrum-beta-lactamase (ESBL)-producing organisms (seven Klebsiella pneumoniae isolates and two Escherichia coli isolates), complete agreement was achieved for eight isolates (one ESBL positive and seven negative); one false positive was obtained with the Phoenix instrument. The MicroScan system correctly detected the 10 ESBL challenge isolates, versus the 6 detected by the Phoenix system. Overall, there was good correlation between the Phoenix instrument and the MicroScan system for the ID and AST of Enterobacteriaceae and common NFGNB. The Phoenix system is a reliable method for the ID and AST of the majority of clinical strains encountered in the clinical microbiology laboratory. Until additional performance data are available, results for all Klebsiella pneumoniae or Klebsiella oxytoca and E. coli isolates screened and confirmed as ESBL producers by any automated system should be confirmed by alternate methods prior to the release of final results.

Because of the high frequency of HLA-DP4 in the Caucasian population, we have selectively delineated HLA-DP4 restricted T cell epitopes in the MAGE-A tumor antigens. We identified 12 good binders to HLA-DP4 and investigated the capacity of the seven best binders to induce in vitro specific CD4+ T cell lines from HLA-DP4 healthy donors. We found that the MAGE-A1 90-104 peptide exhibited a high and constant frequency of CD4+ T cell precursors in all the six tested donors. The MAGE-A1 268-282 peptide was found immunogenic in only two donors but with a high precursor frequency. The MAGE-A12 127-141 peptide was T cell stimulating in six different donors and induced fewer T cell lines. The peptide-specific T cell lines were stimulated by DC loaded with the lysates of cells transfected with MAGE-A1 or MAGE-A12, or loaded with the recombinant protein. We also show that the immunoreactivity of CD4+ T cell epitopes restricted to the same HLA II molecule may vary from one individual to another, as a result of inter-individual variations in the CD4+ T cell repertoire.

HLA-DP4 alleles are carried by 75% of individuals and are the most frequent HLA II alleles worldwide. Because we have recently characterized the peptide-binding specificity of HLA-DP4 molecules, we developed a peptide-binding prediction method to identify HLA-DP4-restricted peptides in multiple Ags. CD4(+) T cell response plays a key role in the immune control of HIV infection, but few HIV-specific T cell epitopes with multi-individual specificity have been identified. They are mostly restricted to HLA-DR molecules, which are very polymorphic molecules. We therefore looked for HLA-DP4-restricted CD4(+) T cell epitopes in the whole genome of HIV. Twenty-one peptides were selected from the HXB2 HIV genome based on the prediction of binding to HLA-DP4 molecules. They were submitted to HLA-DP4-binding assays. Seventeen peptides bound to the HLA-DP401 molecule, whereas 15 peptides bound to HLA-DP402. Six peptides bound very tightly to HLA-DP401 and were investigated for their capacity to induce specific CD4(+) T cell lines in vitro using dendritic cells and CD4(+) T cells collected from eight seronegative HLA-DP4(+) donors. Four peptides from env and reverse transcriptase proteins induced in vitro-specific T cell lines restricted to HLA-DP4 molecules. Peptide-induced T cells recognized variants other than the HXB2 sequence and were stimulated by native Ags processed by immature dendritic cells. The reverse transcriptase peptide is present in 65% of the isolated HIV variants. To our knowledge, we describe the first HIV epitopes restricted to HLA-DP4 molecules.

The current BacT/ALERT SA (BTA SA) aerobic blood culture bottle is made from glass, does not require venting, and contains a liquid emulsion sensor (LES). Its performance has been shown to be equivalent to that of the vented standard aerobic culture bottle. A further-improved version of the BTA SA bottle, designated the BacT/ALERT plastic SA (BTA PSA) culture bottle, is made from clear plastic to prevent breakage, does not require venting, and contains a modified LES (LES 2) to reduce the possibility of false positives. The BTA PSA provides a practical alternative to the current glass version of this bottle. The plastic bottle is also comparable to the current glass bottle in transparency and growth performance and additionally minimizes the exposure to infectious agents due to glass bottle breakage.

The current BacT/Alert standard aerobic (VA) blood culture bottle was redesigned and designated a nonvented aerobic (NVA) culture bottle; this bottle does not require venting. A total of 3,873 sets of blood samples for culture were obtained from adult patients with suspected bacteremia or fungemia. The NVA bottle showed performance equivalent to that of the VA bottle for recovery and speed of detection of microorganisms from blood without the need for venting the bottle.

The authors study the Pancreas divisum's rate in 242 cadavers. With two successive studies, they establish a rate of about 6.6%. They conform the sexual disparity and the presence of muscular fibre cells on a level with papilla duodeni minor.