Quantitative Analysis of Mechanisms That Govern Red Blood Cell Age Structure and Dynamics during Anaemia

Mathematical modelling has proven an important tool in elucidating and quantifying mechanisms that govern the age structure and population dynamics of red blood cells (RBCs). Here we synthesise ideas from previous experimental data and the mathematical modelling literature with new data in order to test hypotheses and generate new predictions about these mechanisms. The result is a set of competing hypotheses about three intrinsic mechanisms: the feedback from circulating RBC concentration to production rate of immature RBCs (reticulocytes) in bone marrow, the release of reticulocytes from bone marrow into the circulation, and their subsequent ageing and clearance. In addition we examine two mechanisms specific to our experimental system: the effect of phenylhydrazine (PHZ) and blood sampling on RBC dynamics. We performed a set of experiments to quantify the dynamics of reticulocyte proportion, RBC concentration, and erythropoietin concentration in PHZ-induced anaemic mice. By quantifying experimental error we are able to fit and assess each hypothesis against our data and recover parameter estimates using Markov chain Monte Carlo based Bayesian inference. We find that, under normal conditions, about 3% of reticulocytes are released early from bone marrow and upon maturation all cells are released immediately. In the circulation, RBCs undergo random clearance but have a maximum lifespan of about 50 days. Under anaemic conditions reticulocyte production rate is linearly correlated with the difference between normal and anaemic RBC concentrations, and their release rate is exponentially correlated with the same. PHZ appears to age rather than kill RBCs, and younger RBCs are affected more than older RBCs. Blood sampling caused short aperiodic spikes in the proportion of reticulocytes which appear to have a different developmental pathway than normal reticulocytes. We also provide evidence of large diurnal oscillations in serum erythropoietin levels during anaemia

A fluoride-free liquid-liquid extraction process for the recovery and separation of niobium and tantalum from alkaline leach solutions

International audienc

Niobium and tantalum processing in oxalic-nitric media: Nb2O5·nH2O and Ta2O5·nH2O precipitation with oxalates and nitrates recycling

International audienceOxalate-based aqueous media represent one of the rare options for solubilizing macroscopic amount of niobium (Nb) and tantalum (Ta) without using toxic fluoride-based mixtures. Recent progress in the hydrometallurgy of Nb and Ta also highlighted the potential of oxalate-nitrate media for the separation of Nb and Ta. Nonetheless, the resulting purified aqueous solutions, containing Nb or Ta in HNO3-H2C2O4 mixtures, need to be further processed in order to yield Nb and Ta solid products that can be commercialized. Furthermore, oxalic acid is relatively expensive in the frame of the hydrometallurgy of Nb and its recycling is necessary. In this study, the precipitation of Nb and Ta, as well as their usual minor impurities (Ti and Fe), from oxalic-nitric acid solutions has been investigated for the first time. Neutralization of Nb-HNO3-H2C2O4 mixtures to pH 7-8 by concentrated NaOH or NH4OH was found to be effective at decomposing the oxalate complexes ([NbO(C2O4)3] 3-and [NbO(C2O4)2(H2O)]-) and precipitating Nb in the form of Nb2O5·nH2O while leaving the Page 2/27 oxalate ions in solution. Taking advantage of the solubility difference between nitrate and oxalate salts, the subsequent concentration of the filtrates yields to the recovery of the oxalates as Na2C2O4 or (NH4)2C2O4·H2O and a concentrated solution of sodium or ammonium nitrate. The developed method exhibits high precipitation yields (>99.9%) for Nb and Ta and high recovery yields (>99%) for the nitrates and oxalates. The process was optimized at the laboratory scale (~50 mL) and then validated on industrial Nb and Ta solutions (~225 L) with successful production of purified Nb2O5·nH2O and Ta2O5·nH2O, recovery of the oxalates in the form of Na2C2O4 or (NH4)2C2O4·H2O and a concentration solution of nitrates. Taking together, the proposed precipitation method and the fluoride-free liquid-liquid Nb-Ta separation recently reported pave the way for more suitable hydrometallurgical processes for Nb and Ta

Community structured model for vaccine strategies to control COVID19 spread: A mathematical study.

Initial efforts to mitigate the COVID-19 pandemic have relied heavily on non-pharmaceutical interventions (NPIs), including physical distancing, hand hygiene, and mask-wearing. However, an effective vaccine is essential to containing the spread of the virus. We developed a compartmental model to examine different vaccine strategies for controlling the spread of COVID-19. Our framework accounts for testing rates, test-turnaround times, and vaccination waning immunity. Using reported case data from the city of Toronto, Canada between Mar-Dec, 2020 we defined epidemic phases of infection using contact rates as well as the probability of transmission upon contact. We investigated the impact of vaccine distribution by comparing different permutations of waning immunity, vaccine coverage and efficacy throughout various stages of NPI's relaxation in terms of cases and deaths. The basic reproduction number is also studied. We observed that widespread vaccine coverage substantially reduced the number of cases and deaths. Under phases with high transmission, an early or late reopening will result in new resurgence of the infection, even with the highest coverage. On the other hand, under phases with lower transmission, 60% of coverage is enough to prevent new infections. Our analysis of R0 showed that the basic reproduction number is reduced by decreasing the tests turnaround time and transmission in the household. While we found that household transmission can decrease following the introduction of a vaccine, public health efforts to reduce test turnaround times remain important for virus containment

Mathematical modelling of vaccination rollout and NPIs lifting on COVID-19 transmission with VOC: a case study in Toronto, Canada

Abstract Background Since December 2020, public health agencies have implemented a variety of vaccination strategies to curb the spread of SARS-CoV-2, along with pre-existing Nonpharmaceutical Interventions (NPIs). Initial strategies focused on vaccinating the elderly to prevent hospitalizations and deaths, but with vaccines becoming available to the broader population, it became important to determine the optimal strategy to enable the safe lifting of NPIs while avoiding virus resurgence. Methods We extended the classic deterministic SIR compartmental disease-transmission model to simulate the lifting of NPIs under different vaccine rollout scenarios. Using case and vaccination data from Toronto, Canada between December 28, 2020, and May 19, 2021, we estimated transmission throughout past stages of NPI escalation/relaxation to compare the impact of lifting NPIs on different dates on cases, hospitalizations, and deaths, given varying degrees of vaccine coverages by 20-year age groups, accounting for waning immunity. Results We found that, once coverage among the elderly is high enough (80% with at least one dose), the main age groups to target are 20–39 and 40–59 years, wherein first-dose coverage of at least 70% by mid-June 2021 is needed to minimize the possibility of resurgence if NPIs are to be lifted in the summer. While a resurgence was observed for every scenario of NPI lifting, we also found that under an optimistic vaccination coverage (70% coverage by mid-June, along with postponing reopening from August 2021 to September 2021) can reduce case counts and severe outcomes by roughly 57% by December 31, 2021. Conclusions Our results suggest that focusing the vaccination strategy on the working-age population can curb the spread of SARS-CoV-2. However, even with high vaccination coverage in adults, increasing contacts and easing protective personal behaviours is not advisable since a resurgence is expected to occur, especially with an earlier reopening