Competitive effects between stationary chemical reaction centres: a theory based on off-center monopoles.

The subject of this paper is competitive effects between multiple reaction sinks. A theory based on off-center monopoles is developed for the steady-state diffusion equation and for the convection-diffusion equation with a constant flow field. The dipolar approximation for the diffusion equation with two equal reaction centres is compared with the exact solution. The former turns out to be remarkably accurate, even for two touching spheres. Numerical evidence is presented to show that the same holds for larger clusters (with more than two spheres). The theory is extended to the convection-diffusion equation with a constant flow field. As one increases the convective velocity, the competitive effects between the reactive centres gradually become less significant. This is demonstrated for a number of cluster configurations. At high flow velocities, the current methodology breaks down. Fixing this problem will be the subject of future research. The current method is useful as an easy-to-use tool for the calibration of other more complicated models in mass and/or heat transfer

Designing a paediatric study for an antimalarial drug including prior information from adults

International audienceThe objectives of this study were to design a pharmacokinetic (PK) study by using information about adults and evaluate the robustness of the recommended design through a case study of mefloquine. PK data about adults and children were available from two different randomized studies of the treatment of malaria with the same artesunate-mefloquine combination regimen. A recommended design for pediatric studies of mefloquine was optimized on the basis of an extrapolated model built from adult data through the following approach. (i) An adult PK model was built, and parameters were estimated by using the stochastic approximation expectation-maximization algorithm. (ii) Pediatric PK parameters were then obtained by adding allometry and maturation to the adult model. (iii) A D-optimal design for children was obtained with PFIM by assuming the extrapolated design. Finally, the robustness of the recommended design was evaluated in terms of the relative bias and relative standard errors (RSE) of the parameters in a simulation study with four different models and was compared to the empirical design used for the pediatric study. Combining PK modeling, extrapolation, and design optimization led to a design for children with five sampling times. PK parameters were well estimated by this design with few RSE. Although the extrapolated model did not predict the observed mefloquine concentrations in children very accurately, it allowed precise and unbiased estimates across various model assumptions, contrary to the empirical design. Using information from adult studies combined with allometry and maturation can help provide robust designs for pediatric studies

Longitudinal instability of slurry pipeline flow

This paper deals with the flow of solid/liquid mixtures through long-distance pipelines. Such flows can be destabilized by the formation of local plugs which may impede or even block the flow. Plugs may develop at the interface between regions of different mean concentration. The driving force for the development of such plugs is the existence of local gradients of the axial flux of solids.A mathematical model is developed which describes this mode of plug formation in slurry pipelines. Several assumptions and approximations enable us to reduce the 3D continuity equation of the solid particles to an effective 1D-equation that contains a concentration-dependent flux function. The latter equation is solved numerically.Illustrative calculations lead to the conclusion that the accumulation of material in a plug does not con- tinue without limit but instead levels off at values that are pumpable under most practical conditions, provided that a certain margin of overdesign is in place

A Randomized Trial of Intravenous Alteplase before Endovascular Treatment for Stroke

The value of administering intravenous alteplase before endovascular treatment (EVT) for acute ischemic stroke has not been studied extensively, particularly in non-Asian populations. METHODS We performed an open-label, multicenter, randomized trial in Europe involving patients with stroke who presented directly to a hospital that was capable of providing EVT and who were eligible for intravenous alteplase and EVT. Patients were randomly assigned in a 1:1 ratio to receive EVT alone or intravenous alteplase followed by EVT (the standard of care). The primary end point was functional outcome on the modified Rankin scale (range, 0 [no disability] to 6 [death]) at 90 days. We assessed the superiority of EVT alone over alteplase plus EVT, as well as noninferiority by a margin of 0.8 for the lower boundary of the 95% confidence interval for the odds ratio of the two trial groups. Death from any cause and symptomatic intracerebral hemorrhage were the main safety end points. RESULTS The analysis included 539 patients. The median score on the modified Rankin scale at 90 days was 3 (interquartile range, 2 to 5) with EVT alone and 2 (interquartile range, 2 to 5) with alteplase plus EVT. The adjusted common odds ratio was 0.84 (95% confidence interval [CI], 0.62 to 1.15; P=0.28), which showed neither superiority nor noninferiority of EVT alone. Mortality was 20.5% with EVT alone and 15.8% with alteplase plus EVT (adjusted odds ratio, 1.39; 95% CI, 0.84 to 2.30). Symptomatic intracerebral hemorrhage occurred in 5.9% and 5.3% of the patients in the respective groups (adjusted odds ratio, 1.30; 95% CI, 0.60 to 2.81). CONCLUSIONS In a randomized trial involving European patients, EVT alone was neither superior nor noninferior to intravenous alteplase followed by EVT with regard to disability outcome at 90 days after stroke. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups

Host range and symptomatology of Pepino mosaic virus strains occurring in Europe

Pepino mosaic virus (PepMV) has caused great concern in the greenhouse tomato industry after it was found causing a new disease in tomato in 1999. The objective of this paper is to investigate alternative hosts and compare important biological characteristics of the three PepMV strains occurring in Europe when tested under different environmental conditions. To this end we compared the infectivity and symptom development of three, well characterized isolates belonging to three different PepMV strains, EU-tom, Ch2 and US1, by inoculating them on tomato, possible alternative host plants in the family Solanaceae and selected test plants. The inoculation experiments were done in 10 countries from south to north in Europe. The importance of alternative hosts among the solanaceous crops and the usefulness of test plants in the biological characterization of PepMV isolates are discussed. Our data for the three strains tested at 10 different European locations with both international and local cultivars showed that eggplant is an alternative host of PepMV. Sweet pepper is not an important host of PepMV, but potato can be infected when the right isolate is matched with a specific cultivar. Nicotiana occidentalis 37B is a useful indicator plant for PepMV studies, since it reacts with a different symptomatology to each one of the PepMV strains.Ravnikar, M.; Blystad, D.; Van Der Vlugt, R.; Alfaro Fernández, AO.; Del Carmen Cordoba, M.; Bese, G.; Hristova, D.... (2015). Host range and symptomatology of Pepino mosaic virus strains occurring in Europe. European Journal of Plant Pathology. 143(1):43-56. doi:10.1007/s10658-015-0664-1S43561431Alfaro-Fernández, A., Córdoba-Sellés, M. C., Herrera-Vásquez, J. A., Cebrián, M. C., & Jordá, C. (2009). Transmission of Pepino mosaic virus by the fungal vector Olpidium virulentus. Journal of Phytopathology, 158, 217–226.Charmichael, D. J., Rey, M. E. C., Naidoo, S., Cook, G., & van Heerden, S. W. (2011). First report of Pepino mosaic virus infecting tomato in South Africa. Plant Disease, 95(6), 767.2.Córdoba, M. C., Martínez-Priego, L., & Jordá, C. (2004). New natural hosts of Pepino mosaic virus in Spain. Plant Disease, 88, 906.Córdoba-Sellés, M. C., García-Rández, A., Alfaro-Fernández, A., & Jordá-Gutiérrez, C. (2007). Seed transmission of pepino mosaic virus and efficacy of tomato seed disinfection treatments. Plant Disease, 91, 1250–1254.Efthimiou, K. E., Gatsios, A. P., Aretakis, K. C., Papayannis, L. C., & Katis, N. I. (2011). First report of Pepino mosaic virus infecting greenhouse cherry tomato in Greece. Plant Disease, 95(1), 78.2.Fakhro, A., von Bargen, S., Bandte, M., Büttner, C., Franken, P., & Schwarz, D. (2011). Susceptibility of different plant species and tomato cultivars to two isolates of Pepino mosaic virus. European Journal of Plant Pathology, 129, 579–590.Gómez, P., Sempere, R. N., Elena, S. F., & Aranda, M. A. (2009). Mixed infections of Pepino mosaic virus strains modulate the evolutionary dynamics of this emergent virus. Journal of Virology, 83, 12378–12387.Hanssen, I. M., Paeleman, A., Wittemans, L., Goen, K., Lievens, B., Bragard, C., Vanachter, A. C. R. C., & Thomma, B. P. H. J. (2008). Genetic characterization of Pepino mosaic virus isolates from Belgian greenhouse tomatoes reveals genetic recombination. European Journal of Plant Pathology, 121, 131–146.Hanssen, I. M., Paeleman, A., Vandewoestijne, E., Van Bergen, L., Bragard, C., Lievens, B., Vanachter, A. C. R. C., & Thomma, B. P. H. J. (2009). Pepino mosaic virus isolates and differential symptomatology in tomato. Plant Pathology, 58, 450–460.Hanssen, I. M., Mumford, R., Blystad, D.-G., Cortez, I., Hasiów-Jaroszewska, B., Hristova, D., Pagán, I., Pereira, A.-M., Peters, J., Pospieszny, H., Ravnikar, M., Stijger, I., Tomassoli, L., Varveri, C., van der Vlugt, R., & Nielsen, S. L. (2010). Seed transmission of Pepino mosaic virus in tomato. European Journal of Plant Pathology, 126, 145–152.Hasiów-Jaroszewska, B., Borodynko, N., Jackowiak, P., Figlerowicz, M., & Pospieszny, H. (2010a). Pepino mosaic virus – a pathogen of tomato crops in Poland: biology, evolution and diagnostics. Journal of Plant Protection Research, 50, 470–476.Hasiów-Jaroszewska, B., Jackowiak, P., Borodynko, N., Figlerowicz, M., & Pospieszny, H. (2010b). Quasispecies nature of Pepino mosaic virus and its evolutionary dynamics. Virus Genes, 41, 260–267.Jeffries, C. J. (1998). FAO/IPGRI technical guidelines for the safe movement of germplasm no. 19. Potato. Food and agriculture organization of the United Nations, Rome/International Plant Genetic Resources Institute, Rome pp 177Jones, R. A. C., Koenig, R., & Lesemann, D. E. (1980). Pepino mosaic virus, a new potexvirus from pepino (Solanum muricatum). Annals of Applied Biology, 94, 61–68.Jordá, C., Lázaro Pérez, A., & Martínez Culebras, P. (2001). First report of Pepino mosaic virus on natural hosts. Plant Disease, 85, 1292.King, A. M. Q., Adams, M. J., Carstens, E. B., Lefkowitz, E. J., (eds). (2012). potexvirus, pp 912–915, in virus taxonomy, classification and nomenclature of viruses; ninth report of the international committee on taxonomy of viruses (p 1327) London, UK: Elsevier Academic PressLing, K.-S., & Zhang, W. (2011). First report of Pepino mosaic virus infecting tomato in Mexico. Plant Disease, 95(8), 1035.Martin, J., & Mousserion, C. (2002). Potato varieties which are sensitive to the tomato strains of Pepino mosaic virus (PepMV). Phytoma Défence Végétaux, 552, 26–28.Mehle, N., Gutierrez-Aguirre, I., Prezelj, N., Delić, D., Vidic, U., & Ravnikar, M. (2014). Survival and transmission of potato virus Y, pepino mosaic virus, and potato spindle tuber viroid in water. Applied and Environmental Microbiology, 80(4), 1455–1462.Moreno-Pérez, M. G., Pagán, I., Aragón-Caballero, L., Cáceres, F., Aurora Fraile, A., & García-Arenal, F. (2014). Ecological and genetic determinants of Pepino mosaic virus emergence. Journal of Virology, 88(6), 3359–3368.Noël, P., Hance, T., & Bragard, C. (2014). Transmission of the pepino mosaic virus by whitefly. European Journal of Plant Pathology, 138, 23–27.Pagan, I., Cordoba-Selles, M. D., Martinez-Priego, L., Fraile, A., Malpica, J. M., Jorda, C., & Garcia-Arenal, F. (2006). Genetic structure of the population of pepino mosaic virus infecting tomato crops in Spain. Phytopathology, 96, 274–279.Papayiannis, L. C., Kokkinos, C. D., & Alfaro-Fernández, A. (2012). Detection, characterization and host range studies of Pepino mosaic virus in Cyprus. European Journal of Plant Pathology, 132, 1–7.Pospieszny, H., Haslow, B., & Borodynko, N. (2008). Characterization of two Polish isolates of Pepino mosaic virus. European Journal of Plant Pathology, 122, 443–445.Salomone, A., & Roggero, P. (2002). Host range, seed transmission and detection by ELISA and lateral flow of an Italian isolate of Pepino mosaic virus. Journal of Plant Pathology, 84, 65–68.Samson, R. G., Allen, T. C., & Whitworth, J. L. (1993). Evaluation of direct tissue blotting to detect potato viruses. American Potato Journal, 70, 257–265.Schwarz, D., Beuch, U., Bandte, M., Fakhro, A., Büttner, C., & Obermeier, C. (2010). Spread and interaction of pepino mosaic virus (PepMV) and pythium aphanidermatum in a closed nutrient solution recirculation system: effects on tomato growth and yield. Plant Pathology, 59(3), 443–452.Shipp, J. L., Buitenhuis, R., Stobbs, L., Wang, K., Kim, W. S., & Ferguson, G. (2008). Vectoring of pepino mosaic virus by bumble-bees in tomato greenhouses. Annals of Applied Biology, 153, 149–155.Van der Vlugt, R. A. A. (2009). Pepino mosaic virus (review). Hellenic Plant Protection Journal, 2, 47–56.Van der Vlugt, R. A. A., & Stijger, C. C. M. M. (2008). Pepino mosaic virus. In B. W. J. Mahy & M. H. V. Van Regenmortel (Eds.), Encyclopedia of virology (5th ed., pp. 103–108). Wageningen: Oxford Elsevier.Van der Vlugt, R. A. A., Stijger, C. C. M. M., Verhoeven, J. T. J., & Lesemann, D.-E. (2000). First report of Pepino mosaic virus on tomato. Plant Disease, 84, 103.Van der Vlugt, R. A. A., Cuperus, C., Vink, J., Stijger, I. C. M. M., Lesemann, D.-E., Verhoeven, J. T. J., & Roenhorst, J. W. (2002). Identification and characterization of Pepino mosaic potexvirus in tomato. Bulletin EPPO/EPPO Bulletin, 32, 503–508.Verchot-Lubicz, J., Chang-Ming, Y., & Bamunusinghe, D. (2007). Molecular biology of potexviruses: recent advances. Journal of General Virology, 88(6), 1643–1655.Verhoeven, J. T. H. J., van der Vlugt, R., & Roenhorst, J. W. (2003). High similarity between tomato isolates of pepino mosaic virus suggests a common origin. European Journal of Plant Pathology, 109, 419–425.Werkman, A.W., & Sansford, C.E. (2010). Pest risk analysis for pepino mosaic virus for the EU. Deliverable Report 4.3. EU Sixth Framework project PEPEIRA. http:// www.pepeira.com .Wright, D., & Mumford, R. (1999). Pepino mosaic potexvirus (PepMV): first records in tomato in the United Kingdom. Plant disease notice (89th ed.). York, UK: Central Science Laboratory

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Competitive effects between stationary chemical reaction centres: a theory based on off-center monopoles.

The subject of this paper is competitive effects between multiple reaction sinks. A theory based on off-center monopoles is developed for the steady-state diffusion equation and for the convection-diffusion equation with a constant flow field. The dipolar approximation for the diffusion equation with two equal reaction centres is compared with the exact solution. The former turns out to be remarkably accurate, even for two touching spheres. Numerical evidence is presented to show that the same holds for larger clusters (with more than two spheres). The theory is extended to the convection-diffusion equation with a constant flow field. As one increases the convective velocity, the competitive effects between the reactive centres gradually become less significant. This is demonstrated for a number of cluster configurations. At high flow velocities, the current methodology breaks down. Fixing this problem will be the subject of future research. The current method is useful as an easy-to-use tool for the calibration of other more complicated models in mass and/or heat transfer

Longitudinal instability of slurry pipeline flow

This paper deals with the flow of solid/liquid mixtures through long-distance pipelines. Such flows can be destabilized by the formation of local plugs which may impede or even block the flow. Plugs may develop at the interface between regions of different mean concentration. The driving force for the development of such plugs is the existence of local gradients of the axial flux of solids.A mathematical model is developed which describes this mode of plug formation in slurry pipelines. Several assumptions and approximations enable us to reduce the 3D continuity equation of the solid particles to an effective 1D-equation that contains a concentration-dependent flux function. The latter equation is solved numerically.Illustrative calculations lead to the conclusion that the accumulation of material in a plug does not con- tinue without limit but instead levels off at values that are pumpable under most practical conditions, provided that a certain margin of overdesign is in place