Solvent Dynamics and Thermodynamics at the Crystal-Solution Interface of Ibuprofen

The choice of solvent is key in the manufacturing of solution-grown crystals due to the critical effect it can exert on their morphology. Here we set out to investigate the dynamics and thermodynamics of solvent molecules at the crystal-solution interface for the morphologically dominant crystal faces of ibuprofen. In particular, we evaluate how thermodynamically favourable the desorption of a solvent molecule is and estimate the rate of exchange of adsorbed solvent molecules with molecules from the bulk solution. This analysis is carried out for all four morphologically dominant crystal faces of ibuprofen {100}, {002}, {011} and {110}, and ten solvents, i.e. water, 1-butanol, toluene, cyclohexanone, cyclohexane, acetonitrile, trichloromethane, methanol, ethyl acetate and ethanol. Our work reveals that the structure of the solution and the exchange dynamics can be strongly dependent on both the crystal face and the solvent, i.e. the same solvent can show radically different structure when in contact with different faces, alternatively the same face can induce different structuring in different solvents. Moreover, we find particularly strong surface-solvent interactions for the {002} and {100} crystal faces in several of the solvents examined. We conclude that the role of desolvation in the growth process is solvent- and face-specific, and therefore it has the potential of impacting the crystal shape anisotropy. We provide a framework to rationalise this effect based on molecular simulations of the crystal/solution interface

Investigating the role of solvent in the formation of vacancies on ibuprofen crystal facets

Surface defects play a crucial role in the process of crystal growth, as incorporation of growth units generally takes place on undercoordinated sites on the growing crystal facet. In this work, we use molecular simulations to obtain information on the role of the solvent in the roughening of three morphologically relevant crystal faces of form I of racemic ibuprofen. To this aim, we devise a computational strategy to evaluate the energetic cost associated with the formation of a surface vacancy for a set of ten solvents, covering a range of polarities and hydrogen bonding propensities. We find that the mechanism as well as the work of defect formation are markedly solvent and facet dependent. Based on Mean Force Integration and Well Tempered Metadynamics, the methodology developed in this work has been designed with the aim of capturing solvent effects at the atomistic scale while maintaining the computational efficiency necessary for implementation in high-throughput in-silico screenings of crystallization solvents

SARS-CoV-2 transmission patterns in educational settings during the Alpha wave in Reggio-Emilia, Italy

: Different monitoring and control policies have been implemented in schools to minimize the spread of SARS-CoV-2. Transmission in schools has been hard to quantify due to the large proportion of asymptomatic carriers in young individuals. We applied a Bayesian approach to reconstruct the transmission chains between 284 SARS-CoV-2 infections ascertained during 87 school outbreak investigations conducted between March and April 2021 in Italy. Under the policy of reactive quarantines, we found that 42.5% (95%CrI: 29.5-54.3%) of infections among school attendees were caused by school contacts. The mean number of secondary cases infected at school by a positive individual during in-person education was estimated to be 0.33 (95%CrI: 0.23-0.43), with marked heterogeneity across individuals. Specifically, we estimated that only 26.0% (95%CrI: 17.6-34.1%) of students and school personnel who tested positive during in-person education caused at least one secondary infection at school. Positive individuals who attended school for at least 6 days before being isolated or quarantined infected on average 0.49 (95%CrI: 0.14-0.83) secondary cases. Our findings provide quantitative insights on the contribution of school transmission to the spread of SARS-CoV-2 in young individuals. Identifying positive cases within 5 days after exposure to their infector could reduce onward transmission at school by at least 30%

Estimation of the incubation period and generation time of SARS-CoV-2 Alpha and Delta variants from contact tracing data

Quantitative information on epidemiological quantities such as the incubation period and generation time of SARS-CoV-2 variants is scarce. We analyzed a dataset collected during contact tracing activities in the province of Reggio Emilia, Italy, throughout 2021. We determined the distributions of the incubation period for the Alpha and Delta variants using information on negative PCR tests and the date of last exposure from 282 symptomatic cases. We estimated the distributions of the intrinsic generation time using a Bayesian inference approach applied to 9724 SARS-CoV-2 cases clustered in 3545 households where at least one secondary case was recorded. We estimated a mean incubation period of 4.9 days (95% credible intervals, CrI, 4.4-5.4) for Alpha and 4.5 days (95%CrI 4.0-5.0) for Delta. The intrinsic generation time was estimated to have a mean of 7.12 days (95% CrI 6.27-8.44) for Alpha and of 6.52 days (95%CrI 5.54-8.43) for Delta. The household serial interval was 2.43 days (95%CrI 2.29-2.58) for Alpha and 2.74 days (95%CrI 2.62-2.88) for Delta, and the estimated proportion of pre-symptomatic transmission was 48-51% for both variants. These results indicate limited differences in the incubation period and intrinsic generation time of SARS-CoV-2 variants Alpha and Delta compared to ancestral lineages

Co-circulation of SARS-CoV-2 Alpha and Gamma variants in Italy, February and March 2021

Background. Several SARS-CoV-2 variants of concern (VOC) have emerged through 2020 and 2021. There is need for tools to estimate the relative transmissibility of emerging variants of SARS-CoV-2 with respect to circulating strains.AimWe aimed to assess the prevalence of co-circulating VOC in Italy and estimate their relative transmissibility.Methods. We conducted two genomic surveillance surveys on 18 February and 18 March 2021 across the whole Italian territory covering 3,243 clinical samples and developed a mathematical model that describes the dynamics of co-circulating strains.Results. The Alpha variant was already dominant on 18 February in a majority of regions/autonomous provinces (national prevalence: 54%) and almost completely replaced historical lineages by 18 March (dominant across Italy, national prevalence: 86%). We found a substantial proportion of the Gamma variant on 18 February, almost exclusively in central Italy (prevalence: 19%), which remained similar on 18 March. Nationally, the mean relative transmissibility of Alpha ranged at 1.55-1.57 times the level of historical lineages (95% CrI: 1.45-1.66). The relative transmissibility of Gamma varied according to the assumed degree of cross-protection from infection with other lineages and ranged from 1.12 (95% CrI: 1.03-1.23) with complete immune evasion to 1.39 (95% CrI: 1.26-1.56) for complete cross-protection.Conclusion. We assessed the relative advantage of competing viral strains, using a mathematical model assuming different degrees of cross-protection. We found substantial co-circulation of Alpha and Gamma in Italy. Gamma was not able to outcompete Alpha, probably because of its lower transmissibility

GM and KM immunoglobulin allotypes in the Galician population: new insights into the peopling of the Iberian Peninsula

<p>Abstract</p> <p>Background</p> <p>The current genetic structure of Iberian populations has presumably been affected by the complex orography of its territory, the different people and civilizations that settled there, its ancient and complex history, the diverse and persistent sociocultural patterns in its different regions, and also by the effects of the Iberian Peninsula representing a refugium area after the last glacial maximum. This paper presents the first data on <it>GM </it>and <it>KM </it>immunoglobulin allotypes in the Galician population and, thus, provides further insights into the extent of genetic diversity in populations settled in the geographic extremes of the Cantabrian region of northern Spain. Furthermore, the genetic relationships of Galicians with other European populations have been investigated.</p> <p>Results</p> <p>Galician population shows a genetic profile for <it>GM </it>haplotypes that is defined by the high presence of the European Mediterranean <it>GM</it>*<it>3 23 5* </it>haplotype, and the relatively high incidence of the African marker <it>GM*1,17 23' 5*</it>. Data based on comparisons between Galician and other Spanish populations (mainly from the north of the peninsula) reveal a poor correlation between geographic and genetic distances (<it>r </it>= 0.30, <it>P </it>= 0.105), a noticeable but variable genetic distances between Galician and Basque subpopulations, and a rather close genetic affinity between Galicia and Valencia, populations which are geographically separated by a long distance and have quite dissimilar cultures and histories. Interestingly, Galicia occupies a central position in the European genetic map, despite being geographically placed at one extreme of the European continent, while displaying a close genetic proximity to Portugal, a finding that is consistent with their shared histories over centuries.</p> <p>Conclusion</p> <p>These findings suggest that the population of Galicia is the result of a relatively balanced mixture of European populations or of the ancestral populations that gave rise to them. This would support the importance of the migratory movements that have taken place in Europe over the course of recent human history and their effects on the European genetic landscape.</p

Electrical conductivity during incipient melting in the oceanic low-velocity zone

International audienceThe low-viscosity layer in the upper mantle, the asthenosphere, is a requirement for plate tectonics1. The seismic low velocities and the high electrical conductivities of the asthenosphere are attributed either to subsolidus, water-related defects in olivine minerals2, 3, 4 or to a few volume per cent of partial melt5, 6, 7, 8, but these two interpretations have two shortcomings. First, the amount of water stored in olivine is not expected to be higher than 50 parts per million owing to partitioning with other mantle phases9 (including pargasite amphibole at moderate temperatures10) and partial melting at high temperatures9. Second, elevated melt volume fractions are impeded by the temperatures prevailing in the asthenosphere, which are too low, and by the melt mobility, which is high and can lead to gravitational segregation11, 12. Here we determine the electrical conductivity of carbon-dioxide-rich and water-rich melts, typically produced at the onset of mantle melting. Electrical conductivity increases modestly with moderate amounts of water and carbon dioxide, but it increases drastically once the carbon dioxide content exceeds six weight per cent in the melt. Incipient melts, long-expected to prevail in the asthenosphere10, 13, 14, 15, can therefore produce high electrical conductivities there. Taking into account variable degrees of depletion of the mantle in water and carbon dioxide, and their effect on the petrology of incipient melting, we calculated conductivity profiles across the asthenosphere for various tectonic plate ages. Several electrical discontinuities are predicted and match geophysical observations in a consistent petrological and geochemical framework. In moderately aged plates (more than five million years old), incipient melts probably trigger both the seismic low velocities and the high electrical conductivities in the upper part of the asthenosphere, whereas in young plates4, where seamount volcanism occurs6, a higher degree of melting is expected

Strong impact of demographic changes on Varicella and Herpes Zoster

Epidemics 4 - Fourth International Conference on Infectious Disease Dynamics , Amsterdam, The Netherlands, November 19-22, 2013 [Poster