Background and Objectives
The efficacy of COVID‐19 convalescent plasma (CP) associates with high titres of antibodies. ConPlas‐19 clinical trial showed that CP reduces the risk of progression to ...severe COVID‐19 at 28 days. Here, we aim to study ConPlas‐19 donors and characteristics that associate with high anti‐SARS‐CoV‐2 antibody levels.
Materials and Methods
Four‐hundred donors were enrolled in ConPlas‐19. The presence and titres of anti‐SARS‐CoV‐2 antibodies were evaluated by EUROIMMUN anti‐SARS‐CoV‐2 S1 IgG ELISA.
Results
A majority of 80.3% of ConPlas‐19 donor candidates had positive EUROIMMUN test results (ratio ≥1.1), and of these, 51.4% had high antibody titres (ratio ≥3.5). Antibody levels decline over time, but nevertheless, out of 37 donors tested for an intended second CP donation, over 90% were still EUROIMMUN positive, and nearly 75% of those with high titres maintained high titres in the second sample. Donors with a greater probability of developing high titres of anti‐SARS‐CoV‐2 antibodies include those older than 40 years of age (RR 2.06; 95% CI 1.24–3.42), with more than 7 days of COVID‐19 symptoms (RR 1.89; 95% CI 1.05–3.43) and collected within 4 months from infection (RR 2.61; 95% CI 1.16–5.90). Male donors had a trend towards higher titres compared with women (RR 1.67; 95% CI 0.91–3.06).
Conclusion
SARS‐CoV‐2 CP candidate donors' age, duration of COVID‐19 symptoms and time from infection to donation associate with the collection of CP with high antibody levels. Beyond COVID‐19, these data are relevant to inform decisions to optimize the CP donor selection process in potential future outbreaks.
Abstract Background Diverse variables are involved in apheresis platelet collection, processing and storage. This survey shows how these are realized in Spain. Method An analysis of collected data ...was performed in a questionnaire completed by ten Transfusion Centers (TC) which perform between 50 and 520 apheresis procedures per month. This information comprises the procedures used to collect, inspect and store apheresis platelet concentrates (PC), and quality control data. Results Macroscopic inspection of PC are performed in all TC, especially during the first few hours post-collection and before distribution. The type of processor, duration of post-collection resting periods and temperature from the time of collection until distribution are similar in all TC. In 80% of TC, PC with small and scarce aggregates are distributed to transfusion services. The presence of clumps is influenced by type of processor, female donor, cold ambient temperature and collection of hyperconcentrated platelets, and is often recurrent in the same donor, although some TC have not found any influential variables. Overall, no objective inspection methods are followed, although there are exceptions. The degree of compliance with quality control parameters, such as the number of units studied, mean platelet yield, residual leukocyte counts and pH at expiry date, is acceptable in all TC. Compliance in terms of number of microbiological culture samples is variable. Discussion The usual practice in Spanish TC with respect to the collection, post-collection handling and storage of apheresis PC can be considered uniform, although some specific aspects of analyses should follow more objective methods.
En el presente artículo se presenta una breve revisión histórica de los esfuerzos teóricos y experimentales en la explicación de las causas y características de la delincuencia femenina.
...Complementado con el análisis de estas características en un a población femenina reclusa en la Prisión Provincial de Alicante.
Autophagy is a highly coordinated process that is controlled at several levels including transcriptional regulation. Here, we identify the transcription factor NFE2L2/NRF2 (nuclear factor, erythroid ...2 like 2) as a regulator of autophagy gene expression and its relevance in a mouse model of Alzheimer disease (AD) that reproduces impaired APP (amyloid β precursor protein) and human (Hs)MAPT/TAU processing, clearance and aggregation. We screened the chromatin immunoprecipitation database ENCODE for 2 proteins, MAFK and BACH1, that bind the NFE2L2-regulated enhancer antioxidant response element (ARE). Using a script generated from the JASPAR's consensus ARE sequence, we identified 27 putative AREs in 16 autophagy-related genes. Twelve of these sequences were validated as NFE2L2 regulated AREs in 9 autophagy genes by additional ChIP assays and quantitative RT-PCR on human and mouse cells after NFE2L2 activation with sulforaphane. Mouse embryo fibroblasts of nfe2l2-knockout mice exhibited reduced expression of autophagy genes, which was rescued by an NFE2L2 expressing lentivirus, and impaired autophagy flux when exposed to hydrogen peroxide. NFE2L2-deficient mice co-expressing HsAPP
V717I
and HsMAPT
P301L
, exhibited more intracellular aggregates of these proteins and reduced neuronal levels of SQSTM1/p62, CALCOCO2/NDP52, ULK1, ATG5 and GABARAPL1. Also, colocalization of HsAPP
V717I
and HsMAPT
P301L
with the NFE2L2-regulated autophagy marker SQSTM1/p62 was reduced in the absence of NFE2L2. In AD patients, neurons expressing high levels of APP or MAPT also expressed SQSTM1/p62 and nuclear NFE2L2, suggesting their attempt to degrade intraneuronal aggregates through autophagy. This study shows that NFE2L2 modulates autophagy gene expression and suggests a new strategy to combat proteinopathies.
Global Navigation Satellite Systems (GNSS) radio occultations allow the vertical sounding of the Earth's atmosphere, in particular, the ionosphere. The physical observables estimated with this ...technique permit to test theoretical models of the electron density such as, for example, the Chapman and the Vary‐Chap models. The former is characterized by a constant scale height, whereas the latter considers a more general function of the scale height with respect to height. We propose to investigate the feasibility of the Vary‐Chap model where the scale height varies linearly with respect to height. In order to test this hypothesis, the scale height data provided by radio occultations from a receiver on board a low Earth orbit (LEO) satellite, obtained by iterating with a local Chapman model at every point of the topside F2 layer provided by the GNSS satellite occultation, are fitted to height data by means of a linear least squares fit (LLS). Results, based on FORMOSAT‐3/COSMIC GPS occultation data inverted by means of the Improved Abel transform inversion technique (which takes into account the horizontal electron content gradients) show that the scale height presents a more clear linear trend above the F2 layer peak height, hm, which is in good agreement with the expected linear temperature dependence. Moreover, the parameters of the linear fit obtained during four representative days for all seasons, depend significantly on local time and latitude, strongly suggesting that this approach can significantly contribute to build realistic models of the electron density directly derived from GNSS occultation data.
Key Points
Results suggest that the scale height is correlated with height in the topside of the ionosphere
The scale height and its gradient depend on local time and latitude
Imbalance between heating and cooling time of the plasma may yield such a linear scale height
The new radio‐occultation (RO) instrument on board the future EUMETSAT Polar System‐Second Generation (EPS‐SG) satellites, flying at a height of 820 km, is primarily focusing on neutral atmospheric ...profiling. It will also provide an opportunity for RO ionospheric sounding, but only below impact heights of 500 km, in order to guarantee a full data gathering of the neutral part. This will leave a gap of 320 km, which impedes the application of the direct inversion techniques to retrieve the electron density profile. To overcome this challenge, we have looked for new ways (accurate and simple) of extrapolating the electron density (also applicable to other low‐Earth orbiting, LEO, missions like CHAMP): a new Vary‐Chap Extrapolation Technique (VCET). VCET is based on the scale height behavior, linearly dependent on the altitude above hmF2. This allows extrapolating the electron density profile for impact heights above its peak height (this is the case for EPS‐SG), up to the satellite orbital height. VCET has been assessed with more than 3700 complete electron density profiles obtained in four representative scenarios of the Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) in the United States and the Formosa Satellite Mission 3 (FORMOSAT‐3) in Taiwan, in solar maximum and minimum conditions, and geomagnetically disturbed conditions, by applying an updated Improved Abel Transform Inversion technique to dual‐frequency GPS measurements. It is shown that VCET performs much better than other classical Chapman models, with 60% of occultations showing relative extrapolation errors below 20%, in contrast with conventional Chapman model extrapolation approaches with 10% or less of the profiles with relative error below 20%.
Key Points
A new electron density profile extrapolation technique (VCET), founded on First Principles, is presented showing a high performance
VCET is simple and accurate: it is based on the linear behavior of the topside scale height, performing 6‐20 times better than Chapman model
The accuracy and extrapolation range, illustrated with FORMOSAT‐3/COSMIC measurements, will be important for new radio‐occultation missions like EPS‐SG
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