The “conscious pilot”—dendritic synchrony moves through the brain to mediate consciousness

Cognitive brain functions including sensory processing and control of behavior are understood as “neurocomputation” in axonal–dendritic synaptic networks of “integrate-and-fire” neurons. Cognitive neurocomputation with consciousness is accompanied by 30- to 90-Hz gamma synchrony electroencephalography (EEG), and non-conscious neurocomputation is not. Gamma synchrony EEG derives largely from neuronal groups linked by dendritic–dendritic gap junctions, forming transient syncytia (“dendritic webs”) in input/integration layers oriented sideways to axonal–dendritic neurocomputational flow. As gap junctions open and close, a gamma-synchronized dendritic web can rapidly change topology and move through the brain as a spatiotemporal envelope performing collective integration and volitional choices correlating with consciousness. The “conscious pilot” is a metaphorical description for a mobile gamma-synchronized dendritic web as vehicle for a conscious agent/pilot which experiences and assumes control of otherwise non-conscious auto-pilot neurocomputation

Quelles sont les motivations des patients à accepter ou à refuser de rentrer dans un protocole d’essai clinique lié à la transplantation ? Quelles connaissances ont ces patients sur les traitements accompagnant la transplantation ?

International audienc

Quelles sont les motivations des patients à accepter ou à refuser de rentrer dans un protocole d’essai clinique lié à la transplantation ? Quelles connaissances ont ces patients sur les traitements accompagnant la transplantation ?

International audienc

Americium recovery from highly active PUREX raffinate by solvent extraction: the EXam process. a review of 10 years of R&D

International audienceIn the framework of the R&D program conducted in France on partitioning and transmutation of minor actinides, a solvent extraction process was developed for separating americium from a PUREX raffinate arising from the dissolution of spent nuclear fuels in nitric acid. The so-called EXAm process uses a mixture of a malonamide (DMDOHEMA, N,N'-dimethyl-N,N'-dioctyl-hexyloxyethylmalonamide) and HDEHP (di-2-ethylhexylphosphoric acid) in organic phase in combination with a water-soluble complexing agent TEDGA (N,N,N',N'tetraethyldiglycolamide) in aqueous phase to enhance Am/Cm separation. Am/ Ln separation is then obtained by selective Am stripping with polyaminocarboxylic acids (HEDTA or DTPA) buffered by citric or malonic acid at low acidity. Started in 2008, an important R&D program was conducted at CEA to optimize and model the process. The feasibility of the direct recovery of Am from a genuine PUREX raffinate by solvent extraction was demonstrated in 2010 and reported, for the first time in the literature. R&D was then conducted to adapt the process for a future scale-up and for application from concentrated PUREX raffinates. The results of the final EXAm process performed on a highly active PUREX concentrate are presented after a summary of 10 years of R&D on this process development

Bisphosphonate sequestering agents. Synthesis and preliminary evaluation for in vitro and in vivo uranium(VI) chelation.

International audienceA library of bisphosphonate-based ligands was prepared using solution-phase parallel synthesis and tested for its uranium-binding properties. With the help of a screening method, based on a chromophoric complex displacement procedure, 23 dipodal and tripodal chelates bearing bisphosphonate chelating functions were found to display very high affinity for the uranyl ion and were selected for evaluation of their in vivo uranyl-removal efficacy. Among them, 11 ligands induced a huge modification of the uranyl biodistribution by deviating the metal from kidney and bones to liver. Among the other ligands, the most potent was the dipodal bisphosphonate 3C which reduced the retention of uranyl and increased its excretion by around 10% of the injected metal

Corticosteroid-Sparing and Optimization of Mycophenolic Acid Exposure in Liver Transplant Recipients Receiving Mycophenolate Mofetil and Tacrolimus

International audienceBACKGROUND:We conducted a randomized multicenter open-label trial in de novo liver transplant recipients to assess the feasibility and potential benefit of a corticosteroid (CS)-free regimen coupled with tacrolimus (Tac) and dose-intensified mycophenolate mofetil (MMF) further adjusted individually.METHODS:Adult liver transplant recipients were randomized on the day of transplantation to a CS-free regimen with Tac and MMF starting at 3 g/d and dose adjusted from day 5 according to mycophenolic acid (MPA) exposure (arm A) or a regimen with CS maintained up to 6 months, Tac and fixed-dose MMF (2 g/d) (arm B). The primary end point was the proportion of patients who experienced treated biopsy-proven acute rejection (BPAR) during the first year posttransplant.RESULTS:One hundred eighty-seven patients were randomized, and 174 comprised the per-protocol population (87 in each arm). The primary objective of noninferiority was met: 7 patients in arm A (8%) and 8 in arm B (9%) experienced treated BPAR in the first year. Two patients in arm A (2%) and 5 in arm B (6%) lost their graft, and 12-month patient survival was similar in both arms (90.8% vs 89.8%; P = 0.86). Adverse events were comparable between arms, except for a lower incidence of de novo diabetes (19.8% vs 32.6%, P = 0.049) and a higher incidence of leukopenia less than 2000/mm (28.6% vs 9.8%; P = 0.001) and neutropenia (26.7% vs 7.9%; P < 0.001) in arm A.CONCLUSIONS:Mycophenolate mofetil at intensified and individually adjusted dose in combination with Tac in de novo liver transplant recipients allows CS discontinuation from day 1 posttransplant with good tolerance and very low rejection incidence

Development and Validation of the QUALI-PALLI-FAM Questionnaire for Assessing Relatives' Perception of Quality of Inpatient Palliative Care: A Prospective Cross-Sectional Survey

International audienceContext: Relatives of patients receiving palliative care are at risk for psychological and physical distress, and their perception of quality of care can influence patients' quality of life. Objectives: The purpose of this study was to develop and validate the QUALI-PALLI-FAM questionnaire (QUAlity of PALLIative car from FAMilies' perspective) to measure families' perception of and satisfaction with palliative care. Methods: An exploratory factor analysis was conducted, and we evaluated the questionnaire's internal consistency using Cronbach's alpha, its stability across various strata, and the correlation between the QUALI-PALLI-FAM (factors, total score, and global satisfaction) and the total score of the FAMCARE (FAMily satisfaction with CARE) questionnaire. Results: This multicentric prospective cross-sectional survey was conducted in seven French hospitals, namely, three palliative care units and four standard medical units with a mobile palliative care team. The questionnaire was completed by 170 relatives of patients (more than 90% of patients had advanced cancer). The final questionnaire included 14 items across three domains: organization of care and availability of caregivers, medical information provision, and confidence and involvement of relatives. Internal consistency was good for all subscales (Cronbach's α = 0.74–0.86). Our questionnaire was stable across various strata: age and gender (patients and relatives), Palliative Performance Scale scores, and care settings. The QUALI-PALLI-FAM total score was correlated with the total FAMCARE score. Conclusion: The QUALI-PALLI-FAM appears to be a valid, reliable, and well-accepted tool to explore relatives' perception of quality of inpatient palliative care and complements the QUALI-PALLI-PAT questionnaire. Further testing is required in various settings and countries

Anti-PLA2R1 antibodies and membranous nephropathy recurrence after kidney transplantation

International audienceIntroductionMembranous nephropathy can lead to end-stage kidney disease, for which kidney transplantation is the preferred therapy. However, the disease often relapses, which can impact allograft survival.MethodsWe conducted a prospective multicenter study in France involving 72 patients with membranous nephropathy who were awaiting and then underwent kidney transplantation. Additionally, we established a retrospective validation cohort of 65 patients. The primary objective was to evaluate the prognostic significance of pre-transplant anti-PLA2R1 antibodies on the recurrence of membranous nephropathy. The study also assessed the incidence rate, time to onset, and risk factors for recurrence, as well as allograft outcome.ResultsThe prospective cohort showed a 26% cumulative incidence of membranous nephropathy recurrence after a median follow-up of 23.5 months. This was confirmed by a 28% cumulative incidence after a median follow-up of 67 months in the retrospective cohort. A strong association was found between the presence of anti-PLA2R1 antibodies prior to transplantation and the risk of disease recurrence (RR=5.9 [CI 95%, 2.3;15.7], p<0.0001). These results were confirmed in the retrospective cohort. Monitoring of anti-PLA2R1 antibodies in the immediate post-transplant period is of limited value, as recurrence occurred early in the first six months (median delay of 5 [3;14] months) after transplantation despite decreasing antibody levels.ConclusionThe presence of anti-PLA2R1 antibodies prior to transplantation was a strong predictor of recurrence of allograft membranous nephropathy. An individualized immunomonitoring and management strategy for kidney transplant candidates with anti-PLA2R1-associated membranous nephropathy should be considered