The last interglacial in the northern North Atlantic and adjacent areas: evidence for a more zonal climate than during the Holocene

We document climate conditions from the last interglacial optimum (LIO) or marine isotope stage 5e (MIS 5e) from terrestrial and oceanic sedimentary archives. Terrestrial climate conditions are reconstructed from pollen assemblages, whereas sea-surface temperature and salinity conditions are estimated from dinocyst assemblages and foraminiferal data (both assemblages and stable isotope composition of carbonate shells). LIO data from the eastern Canadian Arctic and northern Labrador Sea led to reconstruct much higher summer air temperature and seasurface temperature than at present by about 5°C. Data from southeastern Canada and southern Labrador Sea also suggest more thermophilic vegetation and warmer conditions although the contrast between LIO and the Holocene is of lesser amplitude. On the whole, the terrestrial and marine data sets from the northwest North Atlantic and adjacent lands suggest limited influence of southward flow from Arctic waters through the east Greenland and Labrador Currents as compared to the modern situation. The compilation of sea-surface reconstructions from the northwest and northeast North Atlantic indicate much reduced longitudinal contrasts of temperatures than at present, thus a more zonal pattern of circulation. The reconstructions also indicate a lower sea-surface salinity than at present, thus stronger stratification of upper water masses, which would be compatible with a reduced North Atlantic deep-water formation

Estimating a Preference-Based Value Set for the Mental Health Quality of Life Questionnaire (MHQoL)

Background: Health economic evaluations using common health-related quality of life measures may fall short in adequately measuring and valuing the benefits of mental health care interventions. The Mental Health Quality of Life questionnaire (MHQoL) is a standardized, self-administered mental health–related quality of life instrument covering 7 dimensions known to be relevant across and valued highly by people with mental health problems. The aim of this study was to derive a Dutch value set for the MHQoL to facilitate its use in cost-utility analyses. Methods: The value set was estimated using a discrete choice experiment (DCE) with duration that accommodated nonlinear time preferences. The DCE was embedded in a web-based self-complete survey and administered to a representative sample (N = 1,308) of the Dutch adult population. The matched pairwise choice tasks were created using a Bayesian heterogeneous D-efficient design. The overall DCE design comprised 10 different subdesigns, with each subdesign containing 15 matched pairwise choice tasks. Each participant was asked to complete 1 of the subdesigns to which they were randomly assigned. Results: The obtained coefficients indicated that “physical health,”“mood,” and “relationships” were the most important dimensions. All coefficients were in the expected direction and reflected the monotonic structure of the MHQoL, except for level 2 of the dimension “future.” The predicted values for the MHQoL ranged from −0.741 for the worst state to 1 for the best state. Conclusions: This study derived a Dutch value set for the recently introduced MHQoL. This value set allows for the generation of an index value for all MHQoL states on a QALY scale and may hence be used in Dutch cost-utility analyses of mental healthcare interventions. A discrete choice experiment was used to derive a Dutch value set for the MHQoL. This allows the use of the MHQoL in Dutch cost-utility analyses. The dimensions physical health, mood, and relationships were the most important. The utility values range from −0.741 for the worst state to 1 for the best state.</p

Developing and testing a Corona VaccinE tRiAL pLatform (COVERALL) to study Covid-19 vaccine response in immunocompromised patients

BACKGROUND The rapid course of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic calls for fast implementation of clinical trials to assess the effects of new treatment and prophylactic interventions. Building trial platforms embedded in existing data infrastructures is an ideal way to address such questions within well-defined subpopulations. METHODS We developed a trial platform building on the infrastructure of two established national cohort studies: the Swiss human immunodeficiency virus (HIV) Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS). In a pilot trial, termed Corona VaccinE tRiAL pLatform (COVERALL), we assessed the vaccine efficacy of the first two licensed SARS-CoV-2 vaccines in Switzerland and the functionality of the trial platform. RESULTS Using Research Electronic Data Capture (REDCap), we developed a trial platform integrating the infrastructure of the SHCS and STCS. An algorithm identifying eligible patients, as well as baseline data transfer ensured a fast inclusion procedure for eligible patients. We implemented convenient re-directions between the different data entry systems to ensure intuitive data entry for the participating study personnel. The trial platform, including a randomization algorithm ensuring balance among different subgroups, was continuously adapted to changing guidelines concerning vaccination policies. We were able to randomize and vaccinate the first trial participant the same day we received ethics approval. Time to enroll and randomize our target sample size of 380 patients was 22 days. CONCLUSION Taking the best of each system, we were able to flag eligible patients, transfer patient information automatically, randomize and enroll the patients in an easy workflow, decreasing the administrative burden usually associated with a trial of this size

Hourglass SiO2 coating increases the performance of planar patch-clamp.

International audienceObtaining high-throughput electrophysiological recordings is an ongoing challenge in ion channel biophysics and drug discovery. One particular area of development is the replacement of glass pipettes with planar devices in order to increase throughput. However, successful patch-clamp recordings depend on a surface coating which ideally should promote and stabilize giga-seal formation. Here, we present data supporting the use of a structured SiO(2) coating to improve the ability of cells to form a "seal" with a planar patch-clamp substrate. The method is based on a correlation study taking into account structure and size of the pores, surface roughness and chip capacitance. The influence of these parameters on the quality of the seal was assessed. Plasma-enhanced chemical vapour deposition (PECVD) of SiO(2) led to an hourglass structure of the pore and a tighter seal than that offered by a flat, thermal SiO(2) surface. The performance of PECVD chips was validated by recording recombinant potassium channels, BK(Ca), expressed in stable HEK-293 cell lines and in inducible CHO cell lines and low conductance IRK1, and endogenous cationic currents from CHO cells. This multiparametric investigation led to the production of improved chips for planar patch-clamp applications which allow electrophysiological recordings from a wide range of cell lines

Impact of Integrase Inhibitors on Cardiovascular Disease Events in People With Human Immunodeficiency Virus Starting Antiretroviral Therapy

BACKGROUND Integrase strand transfer inhibitors (INSTIs) have been associated with an increased risk for cardiovascular disease (CVD) events. We investigated the impact of starting INSTI-based antiretroviral therapy (ART) on CVD events among treatment-naïve people with human immunodeficiency virus using a target trial framework, which reduces the potential for confounding and selection bias. METHODS We included Swiss HIV Cohort Study participants who were ART-naïve after May 2008, when INSTIs became available in Switzerland. Individuals were categorized according to their first ART regimen (INSTI vs other ART) and were followed from ART start until the first of CVD event (myocardial infarction, stroke, or invasive cardiovascular procedure), loss to follow-up, death, or last cohort visit. We calculated hazard ratios and risk differences using pooled logistic regression models with inverse probability of treatment and censoring weights. RESULTS Of 5362 participants (median age 38 years, 21% women, 15% of African origin), 1837 (34.3%) started INSTI-based ART, and 3525 (65.7%) started other ART. Within 4.9 years (interquartile range, 2.4-7.4), 116 CVD events occurred. Starting INSTI-based ART was not associated with an increased risk for CVD events (adjusted hazard ratio, 0.80; 95% confidence interval [CI], .46-1.39). Adjusted risk differences between individuals who started INSTIs and those who started other ART were -0.17% (95% CI, -.37 to .19) after 1 year, -0.61% (-1.54 to 0.22) after 5 years, and -0.71% (-2.16 to 0.94) after 8 years. CONCLUSIONS In this target trial emulation, we found no difference in short- or long-term risk for CVD events between treatment-naïve people with human immunodeficiency virus who started INSTI-based ART and those on other ART

Impact of integrase inhibitors on cardiovascular disease events in people with HIV starting antiretroviral therapy.

BACKGROUND Integrase strand transfer inhibitors (INSTI) have been associated with an increased risk for cardiovascular disease (CVD) events. We investigated the impact of starting INSTI-based antiretroviral therapy (ART) on CVD events among treatment-naïve people with HIV (PWH) using a target trial framework, which reduces the potential for confounding and selection bias. METHODS We included Swiss HIV Cohort Study participants who were ART-naïve after 05/2008, when INSTI became available in Switzerland. Individuals were categorized according to their first ART regimen (INSTI vs. other ART) and were followed from ART start until the first of CVD event (myocardial infarction, stroke, or invasive cardiovascular procedure), loss to follow-up, death, or last cohort visit. We calculated hazard ratios and risk differences using pooled logistic regression models with inverse probability of treatment and censoring weights. RESULTS Of 5362 participants (median age 38 years, 21% women, 15% of African origin), 1837 (34.3%) started INSTI-based ART, and 3525 (65.7%) started other ART. Within 4.9 years (IQR 2.4-7.4), 116 CVD events occurred. Starting INSTI-based ART was not associated with an increase in CVD events (adjusted hazard ratio 0.80, 95% confidence interval [CI] 0.46-1.39). Adjusted risk differences between individuals who started INSTI and those who started other ART were -0.17% (95% CI -0.37-0.19) after one year, -0.61% (-1.54-0.22) after 5 years, and -0.71% (-2.16-0.94) after 8 years. CONCLUSIONS In this target trial emulation, we found no difference in short or longer term risk for CVD events between treatment-naïve PWH who started INSTI-based and those on other ART

Cournon-d’Auvergne – Carré du Buisson (lotissement Bois Joli 2)

Identifiant de l'opération archéologique : 2006/78 Date de l'opération : 2007 (EX) La commune de Cournon d’Auvergne, située à quelque5km au sud-est de Clermont-Ferrand, s’inscrit entre la grande plaine de La Limagne au nord, la dépression du bassin de Sarliève à l’ouest, bordé lui-même par des collines calcaires et la rivière Allier à l’est. Elle se situe donc au débouché du bassin de l’Allier vers la plaine. Le bassin de Sarliève, qui intéresse plus particulièrement, notre dossier est dominé..

Incorporating Biodiversity into Biogeochemistry Models to Improve Prediction of Ecosystem Services in Temperate Grasslands: Review and Roadmap

Multi-species grasslands are reservoirs of biodiversity and provide multiple ecosystem services, including fodder production and carbon sequestration. The provision of these services depends on the control exerted on the biogeochemistry and plant diversity of the system by the interplay of biotic and abiotic factors, e.g., grazing or mowing intensity. Biogeochemical models incorporate a mechanistic view of the functioning of grasslands and provide a sound basis for studying the underlying processes. However, in these models, the simulation of biogeochemical cycles is generally not coupled to simulation of plant species dynamics, which leads to considerable uncertainty about the quality of predictions. Ecological models, on the other hand, do account for biodiversity with approaches adopted from plant demography, but without linking the dynamics of plant species to the biogeochemical processes occurring at the community level, and this hampers the models’ capacity to assess resilience against abiotic stresses such as drought and nutrient limitation. While setting out the state-of-the-art developments of biogeochemical and ecological modelling, we explore and highlight the role of plant diversity in the regulation of the ecosystem processes underlying the ecosystems services provided by multi-species grasslands. An extensive literature and model survey was carried out with an emphasis on technically advanced models reconciling biogeochemistry and biodiversity, which are readily applicable to managed grasslands in temperate latitudes. We propose a roadmap of promising developments in modelling

Pour un accompagnement global en pension de famille : l’apport des capabilités d’Identité-Logement

Face à l’augmentation constante du nombre de personnes sans domicile en France, le « Plan Logement d'abord 2018-2022 » s’appuie sur les résultats du modèle « Housing First » (HF) pour proposer des solutions de logement pérennes. Il s'agit notamment de pensions de famille qui offrent un logement permanent aux personnes en situation de grande précarité, avec un accompagnement adapté. Si le modèle initial (HF) destiné à un public atteint de troubles psychiques propose un accompagnement orienté vers le rétablissement, l’accompagnement en pension de famille destiné à un public plus large, il nécessite d’être pensé autrement. Par une étude de cas menée en pension de famille, cet article présente une philosophie d’intervention différente où l’accompagnement prendrait appui sur l’approche par les capabilités et sur le concept d’Identité-logement, ouvrant la voie au pragmatisme critique.Faced with the ever-increasing number of homeless people in France, the "Housing First Plan 2018-2022" builds on the results of the "Housing First" (HF) model to propose sustainable solutions. These include boarding houses that provide permanent accommodation for people in very precarious situations, with appropriate support. While the Housing First (HF) model for people with mental health problems offers recovery-oriented support, support in boarding houses for a wider public needs to be considered differently. Through a case study in a boarding house, this article presents a different philosophy of intervention where the support would be based on the capability approach and on the concept of Home-identity, opening the way to critical pragmatism

Antibody Response in Immunocompromised Patients After the Administration of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine BNT162b2 or mRNA-1273: A Randomized Controlled Trial

BACKGROUND BNT162b2 by Pfizer-BioNTech and mRNA-1273 by Moderna are the most commonly used vaccines to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Head-to-head comparison of the efficacy of these vaccines in immunocompromised patients is lacking. METHODS Parallel, 2-arm (allocation 1:1), open-label, noninferiority randomized clinical trial nested into the Swiss HIV Cohort Study and the Swiss Transplant Cohort Study. People living with human immunodeficiency virus (PLWH) or solid organ transplant recipients (SOTR; ie, lung and kidney) from these cohorts were randomized to mRNA-1273 or BNT162b2. The primary endpoint was antibody response to SARS-CoV-2 spike (S1) protein receptor binding domain (Elecsys Anti-SARS-CoV-2 immunoassay, Roche; cutoff ≥0.8 units/mL) 12 weeks after first vaccination (ie, 8 weeks after second vaccination). In addition, antibody response was measured with the Antibody Coronavirus Assay 2 (ABCORA 2). RESULTS A total of 430 patients were randomized and 412 were included in the intention-to-treat analysis (341 PLWH and 71 SOTR). The percentage of patients showing an immune response was 92.1% (95% confidence interval [CI]: 88.4-95.8; 186/202) for mRNA-1273 and 94.3% (95% CI: 91.2-97.4; 198/210) for BNT162b2 (difference: -2.2%; 95% CI: -7.1 to 2.7), fulfilling noninferiority of mRNA-1273. With the ABCORA 2 test, 89.1% had an immune response to mRNA-1273 (95% CI: 84.8-93.4; 180/202) and 89.5% to BNT162b2 (95% CI: 85.4-93.7; 188/210). Based on the Elecsys test, all PLWH had an antibody response (100.0%; 341/341), whereas for SOTR, only 60.6% (95% CI: 49.2-71.9; 43/71) had titers above the cutoff level. CONCLUSIONS In immunocompromised patients, the antibody response of mRNA-1273 was noninferior to BNT162b2. PLWH had in general an antibody response, whereas a high proportion of SOTR had no antibody response