Feasibility of Using 2,3,3,3-Tetrafluoropropene (R1234yf) as a Solvent for Solid–Liquid Extraction of Biopharmaceuticals

Tetrafluoropropene (R1234yf) is the most likely replacement for tetrafluoroethane (R134a), a widely used refrigerant, propellant and solvent, characterised by very high global warming potential. In this study solvation properties of R1234yf were studied experimentally and computationally for solubility of artemisinin, a precursor to the important bio-pharmaceutical API, and extraction of artemisinin from biomass. R1234yf was shown to be a poorer solvent than R134a for artemisinin. COSMO-RS calculations of solvation in R1234yf suggest that the decrease in performance is likely to be due to entropic effects. However, R1234yf was effectively used in solid liquid extraction of Artemisia annua. The new solvent has shown an increased selectivity to the target metabolite artemisinin. This should allow for design of more selective separation processes based on the new solvent molecule with a low global warming potential of 4 relative to CO2.This work was funded under iCON feasibility projects scheme of EPSRC “Centre for Continuous Manufacturing (CMAC)”, EP/IO33459/1. We acknowledge past funding from Medicine for Malaria Ventures for HPLC instrument and funding by University of Cambridge for the LCMS system

Cost-Effectiveness of Rotavirus Vaccination in France-Accounting for Indirect Protection.

BACKGROUND: Vaccination against rotavirus has shown great potential for reducing the primary cause of severe childhood gastroenteritis. Previous economic evaluations of rotavirus vaccination in France have not modeled the potential impact of vaccines on disease burden via reduced transmission. OBJECTIVE: To determine the cost-effectiveness of the introduction of pentavalent rotavirus vaccination into the French infant vaccination schedule. METHODS: We developed an age-structured model of rotavirus transmission calibrated to 6 years of French gastroenteritis incidence and vaccine clinical trial data. We evaluated the cost-effectiveness of pentavalent rotavirus vaccination considering that 75% of infants would receive the three-dose vaccine course. RESULTS: Our model predicts that rotavirus vaccination will decrease rotavirus gastroenteritis incidence and associated clinical outcomes in vaccinated and unvaccinated individuals, delay the seasonal peak of infection, and increase the age of infection. From the societal perspective, our base-case scenario predicts that vaccination coverage would be cost-effective at €115 or €135 per vaccine course at €28,500 and €39,500/quality-adjusted life-year (QALY) gained, respectively, and suggests that almost 95% of the financial benefits will be recouped within the first 5 years following vaccination implementation. From the third-party payer perspective, incremental cost-effectiveness ratios ranged from €12,500 to €20,000/QALY, respectively. Our uncertainty analysis suggests that findings were sensitive to various assumptions including the number of hospitalizations, outpatient visits, and the extent of QALY losses per rotavirus episode. CONCLUSIONS: Introducing pentavalent rotavirus vaccination into the French infant vaccination schedule would significantly reduce the burden of rotavirus disease in children, and could be cost-effective under plausible conditions

Feasibility of Using 2,3,3,3-Tetrafluoropropene (R1234yf) as a Solvent for Solid–Liquid Extraction of Biopharmaceuticals

Tetrafluoropropene (R1234yf) is the most likely replacement for tetrafluoroethane (R134a), a widely used refrigerant, propellant, and solvent, characterized by a very high global warming potential. In this study, solvation properties of R1234yf were studied experimentally and computationally for solubility of artemisinin, a precursor to the important biopharmaceutical API, and extraction of artemisinin from biomass. R1234yf was shown to be a poorer solvent than R134a for artemisinin. COSMO-RS calculations of solvation in R1234yf suggest that the decrease in performance is likely due to entropic effects. However, R1234yf was effectively used in solid–liquid extraction of Artemisia annua. The new solvent has shown an increased selectivity to the target metabolite artemisinin. This should allow for design of more selective separation processes based on the new solvent molecule with a low global warming potential of 4 relative to CO2.This work was funded under iCON feasibility projects scheme of EPSRC “Centre for Continuous Manufacturing (CMAC)”, EP/IO33459/1. We acknowledge past funding from Medicine for Malaria Ventures for HPLC instrument and funding by University of Cambridge for the LCMS system

Towards automation of chemical process route selection based on data mining

A methodology for chemical routes development and evaluation on the basis of data-mining is presented.This work was in part funded by EPSRC project “Terpene-based manufacturing for sustainable chemical feedstocks” EP/K014889

Towards automation of chemical process route selection based on data mining

A methodology for chemical routes development and evaluation on the basis of data-mining is presented. A section of the Reaxys database was converted into a network, which was used to plan hypothetical synthesis routes to convert a bio-waste feedstock, limonene, to a bulk intermediate, benzoic acid. The route evaluation considered process conditions and used multiple indicators, including exergy, E-factor, solvent score, reaction reliability and route redox efficiency, in a multi-criteria environmental sustainability evaluation. The proposed methodology is the first route evaluation based on data mining, explicitly using reaction conditions, and is amenable to full automation.This work was in part funded by EPSRC project “Terpene-based manufacturing for sustainable chemical feedstocks” EP/K014889

An Innovative Influenza Vaccination Policy: Targeting Last Season's Patients

Influenza vaccination is the primary approach to prevent influenza annually. WHO/CDC recommendations prioritize vaccinations mainly on the basis of age and co-morbidities, but have never considered influenza infection history of individuals for vaccination targeting. We evaluated such influenza vaccination policies through small-world contact networks simulations. Further, to verify our findings we analyzed, independently, large-scale empirical data of influenza diagnosis from the two largest Health Maintenance Organizations in Israel, together covering more than 74% of the Israeli population. These longitudinal individual-level data include about nine million cases of influenza diagnosed over a decade. Through contact network epidemiology simulations, we found that individuals previously infected with influenza have a disproportionate probability of being highly connected within networks and transmitting to others. Therefore, we showed that prioritizing those previously infected for vaccination would be more effective than a random vaccination policy in reducing infection. The effectiveness of such a policy is robust over a range of epidemiological assumptions, including cross-reactivity between influenza strains conferring partial protection as high as 55%. Empirically, our analysis of the medical records confirms that in every age group, case definition for influenza, clinical diagnosis, and year tested, patients infected in the year prior had a substantially higher risk of becoming infected in the subsequent year. Accordingly, considering individual infection history in targeting and promoting influenza vaccination is predicted to be a highly effective supplement to the current policy. Our approach can also be generalized for other infectious disease, computer viruses, or ecological networks

GLOSI taxonomy: A tool for ‘seismic risk assessment’ oriented classification of school buildings

For the seismic vulnerability and risk assessment of school infrastructure in a region, it becomes necessary first to identify and classify these constructions into a distinct number of structural typologies characterised by their vulnerability features. This enables us to rank the expected vulnerability of different typologies at the initial screening stage as well as to characterise the representative index buildings of different typologies for detailed vulnerability quantification. Currently, a systematic and comprehensive taxonomy tailored for the school buildings is not available. The present paper thus develops a globally applicable structural taxonomy to be used in the seismic risk assessment of school infrastructure within the framework of the Global Program for Safer Schools (GPSS) of the World Bank. Application as well as verification of the proposed taxonomy is tested to a range of school construction types from different countries across the world

Genomic insights into the taxonomic status of the Bacillus cereus group

The identification and phylogenetic relationships of bacteria within the Bacillus cereus group are controversial. This study aimed at determining the taxonomic affiliations of these strains using the whole-genome sequence-based Genome BLAST Distance Phylogeny (GBDP) approach. The GBDP analysis clearly separated 224 strains into 30 clusters, representing eleven known, partially merged species and accordingly 19–20 putative novel species. Additionally, 16S rRNA gene analysis, a novel variant of multi-locus sequence analysis (nMLSA) and screening of virulence genes were performed. The 16S rRNA gene sequence was not sufficient to differentiate the bacteria within this group due to its high conservation. The nMLSA results were consistent with GBDP. Moreover, a fast typing method was proposed using the pycA gene and where necessary, the ccpA gene. The pXO plasmids and cry genes were widely distributed, suggesting little correlation with the phylogenetic positions of the host bacteria. This might explain why classifications based on virulence characteristics proved unsatisfactory in the past. In summary, this is the first large-scale and systematic study of the taxonomic status of the bacteria within the B. cereus group using whole-genome sequences and is likely to contribute to further insights into their pathogenicity, phylogeny and adaptation to diverse environments

10-[2-(Dimethyl­amino)eth­yl]-9-(4-methoxy­phen­yl)-3,3,6,6-tetra­methyl-3,4,6,7,9,10-hexa­hydro­acridine-1,8(2H,5H)-dione

In the title compound, C28H38N2O3, the central ring of the acridinedione system adopts a boat conformation, while one of the outer rings adopts a half-chair conformation and the conformation of the other outer ring is between a sofa and a half-chair. The acridinedione system is buckled, with an angle of 22.01 (3)°. The crystal packing comprises layers of mol­ecules laid parallel to the ac plane, being reinforced by an intermolecular C—H⋯O interaction