Detection of prions in the plasma of presymptomatic and symptomatic patients with variant Creutzfeldt-Jakob disease

Variant Creutzfeldt-Jakob disease (vCJD) is a human prion disease resulting from the consumption of meat products contaminated by the agent causing bovine spongiform encephalopathy. Evidence supporting the presence of a population of silent carriers that can potentially transmit the disease through blood transfusion is increasing. The development of a blood-screening assay for both symptomatic vCJD patients and asymptomatic carriers is urgently required. We show that a diagnostic assay combining plasminogen-bead capture and protein misfolding cyclic amplification (PMCA) technologies consistently detected minute amounts of abnormal prion protein from French and British vCJD cases in the required femtomolar range. This assay allowed the blinded identification of 18 patients with clinical vCJD among 256 plasma samples from the two most affected countries, with 100% sensitivity [95% confidence interval (CI), 81.5 to 100%], 99.2% analytical specificity (95% CI, 95.9 to 100%), and 100% diagnostic specificity (95% CI, 96.5 to 100%). This assay also allowed the detection of silent carriage of prions 1.3 and 2.6 years before the clinical onset in two blood donors who later developed vCJD. These data provide a key step toward the validation of this PMCA technology as a blood-based diagnostic test for vCJD and support its potential for detecting presymptomatic patients, a prerequisite for limiting the risk of vCJD transmission through blood transfusion

Epidemiology of delayed hemolytic transfusion reaction in adult sickle cell

L’hémolyse post transfusionnelle retardée (HPTR) est une complication potentiellement mortelle de la transfusion dans la drépanocytose. Sa fréquence est sous-estimée et aucun facteur prédictif de sa survenue n'a encore été identifié. Nous avons mené une étude observationnelle prospective monocentrique pendant 30 mois. Nous avons inclus 694 épisodes transfusionnels (ET) chez 311 patients adultes drépanocytaires, divisés en ET ponctuels (ETP = 360) et en ET chronique dans le cadre d’un programme (ETC = 334). Au cours de ce suivi, 15 HPTR ont été enregistrées, exclusivement après un ETP. L'incidence cumulative d’HPTR sur 30 mois était de 4,2 % par ETP (IC 95 % [2,6 ; 6,9]) ou 6,8 % par drépanocytaires transfusés (IC 95 % [4,2 ; 11,3]). Le taux d’incidence était de 16,4 HPTR pour 1000 ETP-Année (IC 95 % [10,1 ; 27,2]) ou 27,1 HPTR pour 1000 Personne-Année (IC 95% [16,7 ; 45,0]). Nous avons étudié 11 HPTR supplémentaires afin de construire un score prédictif. Les variables retenues étaient un antécédent d’HPTR, le nombre d’unités précédemment transfusées et l’état d’immunisation pré transfusionnelle. L’adéquation du score était excellente (Hosmer-Lemeshow = 1,40, p = 0,71), sa capacité discriminante très satisfaisante (aire sous la courbe ROC = 0,85 ; p < 0,0001), une valeur prédictive négative de 98,4 % et une valeur prédictive positive de 50,0 %. La validité interne du score, réalisée par Bootstrap, montre une très bonne performance. Nous rapportons, pour la première fois, l'incidence de l’HPTR et montrons qu’elle survient uniquement suite à un ETP. Nous décrivons également un score simple de prédiction d’une HPTR avant un ETP afin de mieux prendre en charge cette transfusion.Delayed hemolytic transfusion reaction (DHTR) is a life-threatening complication of transfusion in sickle cell disease (SCD). The frequency of DHTR is underestimated and no predictive fac-tors for identifying patients likely to develop DHTR have yet been defined. We conducted a prospective single-center observational study over 30 months. We included 694 transfusion epi-sodes (TE) in 311 adult patients, divided into occasional TE (OTE: 360) and TE during a chronic program (CTE: 334). During follow-up, 15 cases of DHTR were recorded, exclusively after OTEs. DHTR cumulative incidence durin the 30 months was 4.2% per OTE (95% CI [2.6, 6.9]) or 66.8% per patient (95% CI [4.2, 11.3]). The incidence rate was 16.4 DHTR per 1000 OTE-Year (95% CI [10.1, 27.2]) or 27.1 DHTR per 1000 Person-Year (95% CI [16.7 ; 45.0]). We studied 11 additional DHTR cases to construct a score for predicting DHTR after OTE. Fifteen % of the 26 DHTR patients died. The variables retained in the multivariate model were history of DHTR, number of units previously transfused and immunization status before transfusion. The score adequacy was excellent (Hosmer-Lemeshow = 1.40, p = 0.71), very satisfactory dis-criminant capacity (area under ROC curve = 0.85, p <0.0001), negative-predictive value of 98.4% and a positive-predictive value of 50%. The internal validity of the score, realized by Bootstrap, shows a very good performance.We report, for the first time, the incidence of DHTR and we show that DHTR developed only in OTE. We also describe a simple score for predicting DHTR in patients undergoing occasional transfusion, to facilitate the management of blood transfusion in SCD patients

Hyperfonctionnement de la thyroïde et conséquences cardiaques

BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Investigation of Post-Treatment Improving Perovskite Solar Cells Initial Performances and Study of Its Impact on the Durability

Among alternative perovskite device architectures, mesoporous scaffolds based on metal oxide and carbon look highly promising due to their inherent high stability. In this study, the perovskite deposition has been realized on a 1.5 cm2 active surface area using inkjet infiltration through the mesoporous scaffold, affording a clean industrial process for large-scale and stable perovskite devices. A spectacular enhancement of photovoltaic performances from 10% to 14% was then obtained through the implementation of a maturation step. A study of the occurring mechanisms was conducted using a full set of characterization techniques including J-V measurements, UV–visible and PL spectroscopies, LBIC and PL imaging, XRD, and surface roughness measurements. In addition, the impact of this maturation step on the durability of the performances was investigated

Nanoarchitectonics in fully printed perovskite solar cells with carbon-based electrodes

A sacrificial film of polystyrene nanoparticles was utilized to introduce nano-cavities into mesoporous metal oxide layers. This enabled the growth of larger perovskite crystals inside the oxide scaffold with significantly suppressed non-radiative recombination and improved device performance. This work exemplifies potential applications of such nanoarchitectonic approaches in perovskite opto-electronic devices

Carbon-based mesoscopic perovskite solar cells: new insights for promising efficiency and durability enhancements.

International audiencePerovskite materials have a great potential for high efficiency in photovoltaic devices and the best performances have now exceed 26% in single junction. We now need to further develop perovskite device architectures that combine simple industrial development with effective durability. Recently, a novel type of architecture emerged for which no hole transport layer is needed thanks to carbon electrodes which are able to extract photo-generated holes by themselves. Consequently, the use of carbon-based perovskite solar cells (C-PSC) with inexpensive and stable carbon electrode not only enhances the durability of the devices but also reduces fabrication costs.In the presented work, the perovskite deposition has been realized using a final perovskite infiltration through a mesoporous scaffold composed of metal oxide and carbon layers, affording a clean industrial process for large-scale and stable perovskite devices. Different variations will be here explored, including the formulation of the perovskite, the technique of infiltration for the perovskite, the implementation of a post-treatment, and the choice of the encapsulation process. A study of the occurring mechanisms will be conducted using a full set of characterization techniques including J-V measurements, UV-visible and photoluminescence (PL) spectroscopies, light-beam induced current (LBIC) and PL imaging mappings, X-ray diffraction (XRD), Scanning electron microscopy (SEM), Raman spectroscopy and Electrochemical impedance spectroscopy (ESI).Finally, the impact on the durability of photovoltaic performances of all the selected variations will be investigated in order to define the more promising paths to future industrial applications. A special attention will also be given to the method used to measure performances by analyzing J-V curves at different scan rates. Indeed, this allowed us to define boundary conditions allowing the observation of two different states within our devices (defined as ‘stable’ and ‘metastable’). This behavior was interpreted as a structural transition and can vary upon aging according to the selected device configuration

Incidence and predictive score for delayed hemolytic transfusion reaction in adult patients with sickle cell disease

International audienceDelayed hemolytic transfusion reaction (DHTR) is a life-threatening complication of transfusion in sickle cell disease (SCD). The frequency of DHTR is underestimated because its symptoms mimic those of vaso-occlusive crisis and antibodies (Abs) are often not detectable. No predictive factors for identifying patients likely to develop DHTR have yet been defined. We conducted a prospective single-center observational study over 30 months in adult sickle cell patients. We included 694 transfusion episodes (TEs) in 311 patients, divided into occasional TEs (OTEs: 360) and chronic transfusion program (CTEs: 334). During follow-up, 15 cases of DHTR were recorded, exclusively after OTEs. DHTR incidence was 4.2% per OTE (95% CI [2.6; 6.9]) and 6.8% per patient during the 30 months of the study (95% CI [4.2; 11.3]). We studied 11 additional DHTR cases, to construct a predictive score for DHTR. The DHTR mortality is high, 3 (11.5%) of the 26 DHTR patients died. The variables retained in the multivariate model were history of DHTR, number of units previously transfused and immunization status before transfusion. The resulting DHTR-predictive score had an area under the ROC curve of 0.850 [95% CI: 0.780-0.930], a negative-predictive value of 98.4% and a positive-predictive value of 50%. We report in our study population, for the first time, the incidence of DHTR, and, its occurrence exclusively in occasionally transfused patients. We also describe a simple score for predicting DHTR in patients undergoing occasional transfusion, to facilitate the management of blood transfusion in SCD patients

Remanufacturing Perovskite Solar Cells and Modules- a Holistic Case Study

While perovskite photovoltaic (PV) devices are on the verge of their commercialization, promising methods to recycle or remanufacture fully-encapsulated perovskite solar cells (PSCs) and modules are still missing. Through detailed life-cycle assessment shown in this work, we identify that the majority of the greenhouse gas emissions can be reduced by re-using the glass substrate and parts of the PV cells. Based on these analytical findings, we develop a novel thermally-assisted mechanochemical approach to remove the encapsulants, the electrode and the perovskite absorber, allowing to re-use most of the device constituents for remanufacturing PSCs, which recovered nearly 90% of their initial performance. Notably, this the first experimental demonstration of remanufacturing PSCs with an encapsulant and an edge-seal, since potential perovskite solar modules must have them. This pioneering approach distinguishes itself from the “traditional” recycling methods demonstrated in perovskite literature previously by allowing to directly re-use bulk materials with high environmental impact. Thus, such remanufacturing strategy becomes even more favorable than recycling and it allows to save up to 33% of the module’s global warming potential. Remarkably, this process can be universally applied to other PSC architectures, particularly nip-based ones that rely on inorganic metal oxide layers deposited on glass substrates. Finally, we demonstrate that the CO2-footprint of these remanufactured devices can become less than 30g/kWh, which is the value for state-of-the-art c-Si PV modules and can even reach 15g/kWh assuming a similar lifetime

Clinical and laboratory characteristics of symptomatic healthcare workers with suspected COVID-19: a prospective cohort study

International audienceA comprehensive clinical and microbiological assessments of COVID-19 in front-line healthcare workers (HCWs) is needed. Between April 10th and May 28th, 2020, 319 HCWs with acute illness were reviewed. In addition to SARS-CoV-2 RT-PCR screening, a multiplex molecular panel was used for testing other respiratory pathogens. For SARS-CoV-2 positive HCWs, the normalized viral load, viral culture, and virus neutralization assays were performed weekly. For SARS-CoV-2 negative HCWs, SARS-CoV-2 serological testing was performed one month after inclusion. Among the 319 HCWs included, 67 (21.0%) were tested positive for SARS-CoV-2; 65/67 (97.0%) developed mild form of COVID-19. Other respiratory pathogens were found in 6/66 (9.1%) SARS-CoV-2 positive and 47/241 (19.5%) SARS-Cov-2 negative HCWs ( p = 0.07). The proportion of HCWs with a viral load > 5.0 log 10 cp/mL (Ct value  37). More than 90% of cultivable virus had a viral load > 4.5 log 10 cp/mL (Ct < 26) and were collected within 10 days after symptom onset. Among negative HCWs, 6/190 (3.2%) seroconverted. Our data suggest that the determination of viral load can be used for appreciating the infectiousness of infected HCWs. These data could be helpful for facilitating their return to work

Assessment of serological techniques for screening patients for COVID-19 (COVID-SER): a prospective, multicentric study

Introduction The COVID-19 pandemic caused by SARS-CoV-2 threatens global public health, and there is an urgent public health need to assess acquired immunity to SARS-CoV-2. Serological tests might provide results that can be complementary to or confirm suspected COVID-19 cases and reveal previous infection. The performance of serological assays (sensitivity and specificity) has to be evaluated before their use in the general population. The neutralisation capacity of the produced antibodies also has to be evaluated.Methods and analysis We set up a prospective, multicentric clinical study to evaluate the performance of serological kits among a population of healthcare workers presenting mild symptoms suggestive of SARS-CoV-2 infection. Four hundred symptomatic healthcare workers will be included in the COVID-SER study. The values obtained from a control cohort included during the prepandemic time will be used as reference. A workflow was set up to study serological response to SARS-CoV-2 infection and to evaluate antibody neutralisation capacity in patients with a confirmed SARS-CoV-2 infection. The sensitivity and specificity of the tests will be assessed using molecular detection of the virus as a reference. The measurement of IgM and IgG antibodies will be performed once per week for 6 consecutive weeks and then at 6, 12, 18, 24 and 36 months after the diagnosis. The kinetics of IgM and IgG will determine the optimal period to perform serological testing. The proportion of false negative PCR tests in symptomatic subjects will be determined on the basis of subsequent seroconversions.Ethics and dissemination Ethical approval has been obtained from the national review board for biomedical research in April 2020 (Comité de Protection des Personnes Sud Méditerranée I, Marseille, France) (ID RCB 2020-A00932-37). Results will be disseminated through presentations at scientific meetings and publications in peer-reviewed journals.Trial registration number NCT04341142