Late Glacial to Preboreal sea-level rise recorded by the Rhône deltaic system (NW Mediterranean)

International audienceA unique late Glacial–Preboreal record of changes in sea-level and sediment fluxes originating from the Alps is recorded in the Rhône subaqueous delta in the Western Mediterranean Sea. The compilation of detailed bathymetric charts, together with high-resolution seismic profiles and long cores, reveals the detailed architecture of several sediment lobes, related to periods of decreased sea-level rise and/or increased sediment flux. They are situated along the retreat path of the Rhône distributaries, from the shelf edge and canyon heads up to the modern coastline. They form transgressive backstepping parasequences across the shelf, the late Holocene (highstand) deltas being confined to the inner shelf. The most prominent feature is an elongated paleo-shoreface/deltaic system, with an uppermost sandy fraction remolded into subaqueous dunes. A long piston core into the bottomsets of this prograding unit allows precise dating of this ancient deltaic system. In seismic data, it displays aggradation, starting at not, vert, similar 15 cal kyr BP, followed by progradation initiated during the first phase of the Younger Dryas, a period of reduced sea-level rise or stillstand. The delta kept pace with resumed sea-level rise during the Preboreal (which is estimated at about 1 cm/yr), as a result of increased sediment supply from the Alps (melting of glaciers and more humid climate “flushing” the sediment down to the sea). Abandonment of the delta occurred around 10,500 cal yr BP, that is to say about 1000 yr after the end of the Younger Dryas, probably because of decreased sediment flux

Variability in intermediate water circulation of the western Tyrrhenian margin (NE Corsica) over the past 56 kyr

The Marion Dufrene core MD01-2472 made of hemipelagic fine-grained sediments (silt and clays) was collected at 501 m depth on the East Corsica continental slope in 2001 and studied in detail in its 12 uppermost meters. The correlation between sedimentological parameters (Sortable Silt), isotopic data and 14C dating allowed to establish the chronology of main climate events (Younger Dryas/YD, Bölling-Alleröd/B-A, Heinrich events/HS) on this record and to evaluate the impact of major climate oscillations on bottom water condition variability. The sea temperature changes are identified thanks to the planktonic foraminifera assemblages. HS are marked by planktonic foraminifers with peaks of the polar species N. pachyderma (left-coiling), whilst interstadials are marked by warm planktonics that become very abundant during the B-A and Holocene. The occurrence of reworked ostracod species (originating from the continental shelf) and the presence of shallow water Elphidium/Ammonia benthic foraminifera are used to estimate the degree of along-slope transport at the core site. This has revealed two intervals of along-slope transport also associated with coarse-grained contourites, deposited during the YD and HS2 episodes. Intervals with Krithe spp. (ostracod), C. wuellerstorfi (benthic foraminifera) indicate bottom water oxygenation during stadials, whereas interstadials are typified by A. acuminata and Paracypris sp (ostracods) indicating low oxygenated environments. The Last Glacial Maximum is dominated by the planktonic foraminifer T. quinqueloba suggesting high surface primary productivity associated with the establishment of mestrophic bottom conditions. During the Holocene, benthic assemblages indicate oligo-mesotrophic conditions and weak hydrodynamic bottom regime. We hypothesize that there is relationship between the Levantine Intermediate Water (LIW) intensification during cold rapid climate events and benthic fauna assemblages due to changes in: 1) bottom water ventilation, corresponding to a significant reinforcement of the LIW velocity, and 2) the export of nutrients (generating changes in trophic conditions) and/or sediment particles by bottom currents (contributing to the formation of contourites)

Contrasting intensity of aragonite dissolution and dolomite cementation in glacial versus interglacial intervals of a subtropical carbonate succession

Aragonite and high-Mg calcite are abundant in modern, neritic carbonate systems but almost absent in their fossil counterparts. Dissolution of these metastable mineral phases commonly leaves no visible trace in the sedimentary record, compromising the derivation of palaeoenvironmental information from the rock record. The upper 25 m of Integrated Ocean Drilling Program (IODP) Site U1460 on the outer ramp of the western Australian Shelf were investigated to study shallow burial (tens of metres) marine diagenesis in organic-carbon poor sediments using microscopic, total organic carbon, biomarkers and mineralogical analysis in combination with porewater geochemistry. Aragonite dissolution is negligible at the seafloor but intensifies ca 5 m below, even though bulk porewaters are supersaturated for aragonite. This apparent contradiction likely results from dissolution in undersaturated microenvironments. Aragonite dissolution below 5 to 6 m is on average more intense in interglacial compared to glacial intervals. The presence of disseminated framboidal pyrite and porewater results indicate that minor sulphate reduction is active at IODP Site U1460. Sulphate reduction is probably limited by the low organic matter content (ca 0.2%). It is well-known from the literature that incipient sulphate reduction can lead to a drop in pH and consequently to carbonate dissolution. It is therefore assumed that the slightly higher concentration of organic matter in the interglacial intervals allowed increased aragonite dissolution during sulphate reduction compared to glacial beds. Low amounts of dolomite cement (<15%) start to form at the same depth (5 to 6 m) as aragonite dissolution intensifies. Dolomite formation and aragonite dissolution also show covariance on a metre-scale below 5 to 6 m, indicating that a low carbonate saturation state might enhance dolomite formation. This mechanism provides an indirect link between dolomite formation, aragonite dissolution and orbital cycles. The outcome of this study, therefore, contributes to a better understanding of differential diagenesis in marine carbonates

Deltaic and Coastal Sediments as Recorders of Mediterranean Regional Climate and Human Impact Over the Past Three Millennia

This work was financially supported by the MISTRALS/PaleoMex program and by the Project of Strategic Interest NextData PNR 2011–2013 (www. nextdataproject.it). Lionel Savignan is thanked for his participation in the biomarker analysis. Radiocarbon datings for core KESC9-14 have been funded by Institut Carnot Ifremer-EDROME (grant A0811101). We also thank the Holocene North-Atlantic Gyres and Mediterranean Overturning dynamic through Climate Changes (HAMOC) project for financial support. The biomarker data presented here are available in the supporting information.Peer reviewedPublisher PD

Deltaic and Coastal Sediments as Recorders of Mediterranean Regional Climate and Human Impact Over the Past Three Millennia

International audienc

Ceftolozane/Tazobactam for Treatment of Severe ESBL-Producing Enterobacterales Infections: A Multicenter Nationwide Clinical Experience (CEFTABUSE II Study)

Background. Few data are reported in the literature about the outcome of patients with severe extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) infections treated with ceftolozane/tazobactam (C/T), in empiric or definitive therapy.Methods. A multicenter retrospective study was performed in Italy (June 2016-June 2019). Successful clinical outcome was defined as complete resolution of clinical signs/symptoms related to ESBL-E infection and lack of microbiological evidence of infection. The primary end point was to identify predictors of clinical failure of C/T therapy.Results. C/T treatment was documented in 153 patients: pneumonia was the most common diagnosis (n = 46, 30%), followed by 34 cases of complicated urinary tract infections (22.2%). Septic shock was observed in 42 (27.5%) patients. C/T was used as empiric therapy in 46 (30%) patients and as monotherapy in 127 (83%) patients. Favorable clinical outcome was observed in 128 (83.7%) patients; 25 patients were considered to have failed C/T therapy. Overall, 30-day mortality was reported for 15 (9.8%) patients. At multivariate analysis, Charlson comorbidity index &gt;4 (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.9-3.5; P = .02), septic shock (OR, 6.2; 95% CI, 3.8-7.9; P &lt; .001), and continuous renal replacement therapy (OR, 3.1; 95% CI, 1.9-5.3; P = .001) were independently associated with clinical failure, whereas empiric therapy displaying in vitro activity (OR, 0.12; 95% CI, 0.01-0.34; P &lt; .001) and adequate source control of infection (OR, 0.42; 95% CI, 0.14-0.55; P &lt; .001) were associated with clinical success.Conclusions. Data show that C/T could be a valid option in empiric and/or targeted therapy in patients with severe infections caused by ESBL-producing Enterobacterales. Clinicians should be aware of the risk of clinical failure with standard-dose C/T therapy in septic patients receiving CRRT

Risk Factors and Outcomes of Candidemia Caused by Biofilm-Forming Isolates in a Tertiary Care Hospital

Very few data exist on risk factors for developing biofilm-forming Candida bloodstream infection (CBSI) or on variables associated with the outcome of patients treated for this infection. METHODS AND FINDINGS: We identified 207 patients with CBSI, from whom 84 biofilm-forming and 123 non biofilm-forming Candida isolates were recovered. A case-case-control study to identify risk factors and a cohort study to analyze outcomes were conducted. In addition, two sub-groups of case patients were analyzed after matching for age, sex, APACHE III score, and receipt of adequate antifungal therapy. Independent predictors of biofilm-forming CBSI were presence of central venous catheter (odds ratio [OR], 6.44; 95% confidence interval [95% CI], 3.21-12.92) or urinary catheter (OR, 2.40; 95% CI, 1.18-4.91), use of total parenteral nutrition (OR, 5.21; 95% CI, 2.59-10.48), and diabetes mellitus (OR, 4.47; 95% CI, 2.03-9.83). Hospital mortality, post-CBSI hospital length of stay (LOS) (calculated only among survivors), and costs of antifungal therapy were significantly greater among patients infected by biofilm-forming isolates than those infected by non-biofilm-forming isolates. Among biofilm-forming CBSI patients receiving adequate antifungal therapy, those treated with highly active anti-biofilm (HAAB) agents (e.g., caspofungin) had significantly shorter post-CBSI hospital LOS than those treated with non-HAAB antifungal agents (e.g., fluconazole); this difference was confirmed when this analysis was conducted only among survivors. After matching, all the outcomes were still favorable for patients with non-biofilm-forming CBSI. Furthermore, the biofilm-forming CBSI was significantly associated with a matched excess risk for hospital death of 1.77 compared to non-biofilm-forming CBSI. CONCLUSIONS: Our data show that biofilm growth by Candida has an adverse impact on clinical and economic outcomes of CBSI. Of note, better outcomes were seen for those CBSI patients who received HAAB antifungal therapy

A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death

: The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value < 5.0 × 10-8) association of the rs117011822 variant, on chromosome 11, of rs7208524 on chromosome 17, approaching the genome-wide threshold (P-value = 5.19 × 10-8). A total of 113 variants were associated with survival at P-value < 1.0 × 10-5 and most of them regulated the expression of genes involved in immune response (e.g., CD300 and KLR genes), or in lung repair and function (e.g., FGF19 and CDH13). Overall, our results suggest that germline variants may modulate COVID-19 risk of death, possibly through the regulation of gene expression in immune response and lung function pathways

Host genetics and COVID-19 severity: increasing the accuracy of latest severity scores by Boolean quantum features

The impact of common and rare variants in COVID-19 host genetics has been widely studied. In particular, in Fallerini et al. (Human genetics, 2022, 141, 147–173), common and rare variants were used to define an interpretable machine learning model for predicting COVID-19 severity. First, variants were converted into sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. After that, the Boolean features, selected by these logistic models, were combined into an Integrated PolyGenic Score (IPGS), which offers a very simple description of the contribution of host genetics in COVID-19 severity.. IPGS leads to an accuracy of 55%–60% on different cohorts, and, after a logistic regression with both IPGS and age as inputs, it leads to an accuracy of 75%. The goal of this paper is to improve the previous results, using not only the most informative Boolean features with respect to the genetic bases of severity but also the information on host organs involved in the disease. In this study, we generalize the IPGS adding a statistical weight for each organ, through the transformation of Boolean features into “Boolean quantum features,” inspired by quantum mechanics. The organ coefficients were set via the application of the genetic algorithm PyGAD, and, after that, we defined two new integrated polygenic scores (IPGSph1 and IPGSph2). By applying a logistic regression with both IPGS, (IPGSph2 (or indifferently IPGSph1) and age as inputs, we reached an accuracy of 84%–86%, thus improving the results previously shown in Fallerini et al. (Human genetics, 2022, 141, 147–173) by a factor of 10%

WHO global research priorities for antimicrobial resistance in human health

The WHO research agenda for antimicrobial resistance (AMR) in human health has identified 40 research priorities to be addressed by the year 2030. These priorities focus on bacterial and fungal pathogens of crucial importance in addressing AMR, including drug-resistant pathogens causing tuberculosis. These research priorities encompass the entire people-centred journey, covering prevention, diagnosis, and treatment of antimicrobial-resistant infections, in addition to addressing the overarching knowledge gaps in AMR epidemiology, burden and drivers, policies and regulations, and awareness and education. The research priorities were identified through a multistage process, starting with a comprehensive scoping review of knowledge gaps, with expert inputs gathered through a survey and open call. The priority setting involved a rigorous modified Child Health and Nutrition Research Initiative approach, ensuring global representation and applicability of the findings. The ultimate goal of this research agenda is to encourage research and investment in the generation of evidence to better understand AMR dynamics and facilitate policy translation for reducing the burden and consequences of AMR