Publications

Effects of recombination on multi-drug resistance evolution in Plasmodium falciparum malaria

Published in PLoS Computational Biology, 2024

When multiple beneficial alleles at multiple loci are present in a population but not linked together in any one individual, there is no general evolutionary result that determines whether recombination will speed up or slow down the emergence and evolution of genotypes carrying multiple beneficial alleles. Translated to infectious disease control, this evolutionary uncertainty means that when multiple types of drug resistance are present we do not know whether recombination will act more strongly to (1) bring together single-resistant genotypes into multi-drug resistant (MDR) genotypes, or (2) break apart MDR genotypes into single-resistant genotypes. In this paper, we introduce a new version of an established and validated individual-based malaria transmission model where we have added 25 drug-resistance related loci, individual mosquito bites, and mosquitoes feeding on multiple hosts in a single meal (interrupted feeds) allowing for recombination events of different Plasmodium falciparum genotypes from different hosts. Recombination among P. falciparum genotypes in this model occurs from two sources of variation, multi-clonal infections in single hosts and interrupted feeds on multiple hosts, and we show that 80% to 97% of MDR recombinant falciparum genotypes are projected to occur from single uninterrupted bites on hosts with multi-clonal infections (for malaria prevalence>5%). Increases in the model’s interrupted feeding rate slowly increase the number of recombination events occurring from interrupted feeds. A comparison of drug-resistance management strategies with this new model shows that, over a 15-year timeframe, triple artemisinin-combination therapies (ACT) strategies show the largest reductions in treatment failures and the longest delays until artemisinin resistance reaches a critical 1% threshold. Multiple first-line therapies (MFT) are second best under these criteria, and ACT cycling approaches are third best. When compared to cycling strategies, MFT strategies generate a greater diversity of recombinant genotypes but fewer recombination events generating MDR and slower emergence of these recombinant MDR genotypes.

Recommended citation: Tran K.T., Nguyen T.D., Weissman D.B., Li E.Z., Mok S., Small-Saunders J.L., Bousema T., Zupko, R.J., Tran, T.N.A, Boni, M.F. (2025) Effects of recombination on multi-drug resistance evolution in Plasmodium falciparum malaria. PLoS Computational Biology 21(8): e1013401. https://doi.org/10.1371/journal.pcbi.1013401 https://doi.org/10.1371/journal.pcbi.1013401 | Download Manuscript

Role of seasonal importation and genetic drift on selection for drug-resistant genotypes of Plasmodium falciparum in high-transmission settings

Published in Journal of The Royal Society Interface, 2024

Historically Plasmodium falciparum has followed a pattern of drug resistance first appearing in low-transmission settings before spreading to high-transmission settings. Several features of low-transmission regions are hypothesized as explanations: higher chance of symptoms and treatment seeking, better treatment access, less within-host competition among clones and lower rates of recombination. Here, we test whether importation of drug-resistant parasites is more likely to lead to successful emergence and establishment in low-transmission or high-transmission periods of the same epidemiological setting, using a spatial, individual-based stochastic model of malaria and drug-resistance evolution calibrated for Burkina Faso. Upon controlling for the timing of importation of drug-resistant genotypes and examination of key model variables, we found that drug-resistant genotypes imported during the low-transmission season were (i) more susceptible to stochastic extinction due to the action of genetic drift, and (ii) more likely to lead to establishment of drug resistance when parasites are able to survive early stochastic loss due to drift. This implies that rare importation events are more likely to lead to establishment if they occur during a high-transmission season, but that constant importation (e.g. neighbouring countries with high levels of resistance) may produce a greater risk during low-transmission periods.

Recommended citation: Zupko, R. J., Servadio, J. L., Nguyen, T. D., Tran, T. N.-A., Tran, K. T., Somé, A. F., & Boni, M. F. (2024). Role of seasonal importation and genetic drift on selection for drug-resistant genotypes of Plasmodium falciparum in high-transmission settings. Journal of The Royal Society Interface, 21(212), 20230619. doi: 10.1098/rsif.2023.0619 https://doi.org/10.1098/rsif.2023.0619 | Download Manuscript

Modeling policy interventions for slowing the spread of artemisinin-resistant pfkelch R561H mutations in Rwanda

Published in Nature Medicine, 2023

Artemisinin combination therapies (ACTs) are highly effective at treating uncomplicated Plasmodium falciparum malaria, but the emergence of the new pfkelch13 R561H mutation in Rwanda, associated with delayed parasite clearance, suggests that interventions are needed to slow its spread. Using a Rwanda-specific spatial calibration of an individual-based malaria model, we evaluate 26 strategies aimed at minimizing treatment failures and delaying the spread of R561H after 3, 5 and 10 years. Lengthening ACT courses and deploying multiple first-line therapies (MFTs) reduced treatment failures after 5 years when compared to the current approach of a 3-d course of artemether–lumefantrine. The best among these options (an MFT policy) resulted in median treatment failure counts that were 49% lower and a median R561H allele frequency that was 0.15 lower than under baseline. New approaches to resistance management, such as triple ACTs or sequential courses of two different ACTs, were projected to have a larger impact than longer ACT courses or MFT; these were associated with median treatment failure counts in 5 years that were 81–92% lower than the current approach. A policy response to currently circulating artemisinin-resistant genotypes in Africa is urgently needed to prevent a population-wide rise in treatment failures.

Recommended citation: Zupko, R. J., Nguyen, T. D., Ngabonziza, J. C. S., Kabera, M., Li, H., Tran, T. N.-A., Tran, K. T., Uwimana, A., & Boni, M. F. (2023). Modeling policy interventions for slowing the spread of artemisinin-resistant pfkelch R561H mutations in Rwanda. Nature Medicine. https://doi.org/10.1038/s41591-023-02551-w | Download Manuscript

Torrefied plastic-fiber fuel pellets as a replacement for fossil fuels — a case study life cycle assessment for Green Bay, Wisconsin, USA

Published in The International Journal of Life Cycle Assessment, 2023

Purpose: The commercial-scale production of torrefied plastic-fiber fuel pellets from waste plastics and waste fibers may offer a viable alternative to fossil fuel–based energy. In this study, the environmental impact of fuel pellets produced and consumed in Green Bay, Wisconsin, USA is evaluated and compared to the status quo of grid energy production from fossil fuels (i.e., coal or natural gas).
Methods: A cradle-to-grave life cycle assessment was conducted using a functional unit of 1 kWh of energy produced using torrefied plastic-fiber fuel pellets versus production of energy from coal or natural gas. Regional data along with relevant manufacturing data was used to inform the inventory of the production of the torrefied fuel pellets, which are manufactured using waste fibers and waste plastics sourced from within 5 km of the torrefaction facility and consumed within 50 km of the facility. Since fuel pellets are produced from waste inputs and contain biogenic carbon sources, impacts were assessed with/without credit for biogenic carbon and with/without the burden of the torrefaction inputs.
Results and discussion: The production of 1 kWh of energy using torrefied plastic-fiber fuel pellets was determined to produce between 0.303 and 0.757 kg CO₂ eq emissions due to combustion and between 0.062 and 1.105 kg CO₂ eq additional emissions as a result of the manufacturing process, with the ranges dependent upon the allocation method selected. Under a burden-free allocation due to waste materials used as inputs, along with a credit for biogenic carbon emissions, the system produces 0.365 kg CO₂ eq per 1 kWh of energy; however, under a full-burden allocation with no credit for biogenic carbon emissions, 1.862 kg CO₂ eq per 1 kWh of energy is produced. This highlights the differences between allocation scenarios and role of credits for biogenic carbon emissions when evaluating systems.
Conclusions: The usage of torrefied plastic-fiber fuel pellets produced using waste plastics and fibers is a reasonable alternative to the status quo of waste disposal coupled with the production of grid energy from fossil fuels. In addition to the reduction in GHG emissions, the use of the process would also help to alleviate the environmental burden of waste plastics.

Recommended citation: Zupko, R., Kolapkar, S. S., & Zinchik, S. (2023). Torrefied plastic-fiber fuel pellets as a replacement for fossil fuels—A case study life cycle assessment for Green Bay, Wisconsin, USA. The International Journal of Life Cycle Assessment. https://doi.org/10.1007/s11367-023-02198-2 | Download Manuscript

Externalities as the status quo: Federal application of environmental charges in the United States

Published in Environmental Policy and Governance, 2023

Conceptualized as early as 1920 by English economist Arthur Cecil Pigou, but not formalized until later work in the 1970s and 1990s, 'environmental charges' suggest the revenue burden of governance could be shifted from economic 'goods' to environmental 'bads.' While their association with Pigouvian taxes would suggest that environmental charges are applied as a policy instrument to encourage the reduction or elimination of environmental externalities, their application at the federal level in the United States suggests this is not the case. As part of a review of environmental charges in the United States, this paper postulates that federally applied environmental charges accept environmental externalities as the status quo and are instead intended to recover the government's cost in addressing the environmental externality in conformance with the polluter pays principle.

Recommended citation: Zupko, R. (2023). Externalities as the status quo: Federal application of environmental charges in the United States. Environmental Policy and Governance. 33(1), 78-89. https://doi.org/10.1002/eet.1997

National-scale simulation of human movement in a spatially coupled individual-based model of malaria in Burkina Faso

Published in Scientific Reports, 2023

Malaria due to the Plasmodium falciparum parasite remains a threat to human health despite eradication efforts and the development of anti-malarial treatments, such as artemisinin combination therapies. Human movement and migration have been linked to the propagation of malaria on national scales, highlighting the need for the incorporation of human movement in modeling efforts. Spatially couped individual-based models have been used to study how anti-malarial resistance evolves and spreads in response to drug policy changes; however, as the spatial scale of the model increases, the challenges associated with modeling of movement also increase. In this paper we discuss the development, calibration, and validation of a movement model in the context of a national-scale, spatial, individual-based model used to study the evolution of drug resistance in the malaria parasite.

Recommended citation: Zupko, R. J., Nguyen, T. D., Wesolowski, A., Gerardin, J., & Boni, M. F. (2023). National-scale simulation of human movement in a spatially coupled individual-based model of malaria in Burkina Faso. Scientific Reports, 13(1), 321. https://doi.org/10.1038/s41598-022-26878-5

Long-term effects of increased adoption of artemisinin combination therapies in Burkina Faso

Published in PLOS Global Public Health, 2022

Artemisinin combination therapies (ACTs) are the WHO-recommended first-line therapies for uncomplicated Plasmodium falciparum malaria. The emergence and spread of artemisinin-resistant genotypes is a major global public health concern due to the increased rate of treatment failures that result. This is particularly germane for WHO designated ‘high burden to high impact’ (HBHI) countries, such as Burkina Faso, where there is increased emphasis on improving guidance, strategy, and coordination of local malaria response in an effort to reduce the prevalence of P. falciparum malaria. To explore how the increased adoption of ACTs may affect the HBHI malaria setting of Burkina Faso, we added spatial structure to a validated individual-based stochastic model of P. falciparum transmission and evaluated the long-term effects of increased ACT use. We explored how de novo emergence of artemisinin-resistant genotypes, such as pfkelch13 580Y, may occur under scenarios in which private-market drugs are eliminated or multiple first-line therapies (MFT) are deployed. We found that elimination of private market drugs would result in lower treatment failures rates (between 11.98% and 12.90%) when compared to the status quo (13.11%). However, scenarios incorporating MFT with equal deployment of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PPQ) may accelerate near-term drug resistance (580Y frequency ranging between 0.62 to 0.84 in model year 2038) and treatment failure rates (26.69% to 34.00% in 2038), due to early failure and substantially reduced treatment efficacy resulting from piperaquine-resistant genotypes. A rebalanced MFT approach (90% AL, 10% DHA-PPQ) results in approximately equal long-term outcomes to using AL alone but may be difficult to implement in practice.

Recommended citation: Zupko, R. J., Nguyen, T. D., Somé, A. F., Tran, T. N.-A., Gerardin, J., Dudas, P., Giang, D. D. H., Tran, K. T., Wesolowski, A., Ouédraogo, J.-B., & Boni, M. F. (2022). Long-term effects of increased adoption of artemisinin combination therapies in Burkina Faso. PLoS Glob. Public Health, 2(2), e0000111. https://doi.org/10.1371/journal.pgph.0000111

Simulating Human Movement in a National-Scale Individual-Based Model of Malaria in Burkina Faso

Published in Social Simulation Conference 2021, 2021

Malaria due to the Plasmodium falciparum parasite remains a threat to human health despite eradication efforts and the development of anti-malarial treatments, such as artemisinin-based combination therapies. Human movement and migration have been linked to the propagation of malaria on national scales, highlighting the need for the incorporation of human movement in modeling efforts. Individual-based models have been used to study how anti-malarial resistance evolves and spreads in response to drug policy changes; however, as the spatial scale of the model increases, the challenges associated with modeling of movement also increase. In this paper we discuss the development, calibration, and validation of a movement model in the context of a national-scale, spatial, individual-based model used to study the evolution of drug resistance in the malaria parasite.

Recommended citation: Zupko, R., Nguyen, T. D., Boni, M. F., & Kraków, I. (2021, September). Simulating Human Movement in a National-Scale Individual-Based Model of Malaria in Burkina Faso. In Social Simulation Conference 2021(pp. 20-24). Download Manuscript

Application of agent-based modeling and life cycle sustainability assessment to evaluate biorefinery placement

Published in Biomass and Bioenergy, 2020

Biofuels, such as those derived from woody biomass, are being developed as one part of a renewable energy portfolio; however, it remains unclear if they can be sustainably developed. This manuscript demonstrates that the use of agent-based modeling (ABM) and life cycle sustainability assessment (LCSA) as part of an integrated methodology allows for robust assessment of the possible impacts. A case study of a proposed biorefinery in Ontonagon, Michigan, USA is conducted. In the case study, ABM is used to project the harvest decision making of forest owners and loggers to determine if they were willing to harvest and supply woody biomass to the biorefinery under several different price points. The results from the ABM were used to inform inventory data for projections of environmental impacts, along with projected impacts for economic and social concerns. The results of the case study show that while Ontonagon is a promising site for a biorefinery, the quantity of woody biomass delivered is a concern along with potential impacts to wetlands in the region. Ultimately, this case study suggestions that the integration of ABM and LCSA may be effective the assessment of other biorefineries.

Recommended citation: Zupko, R. (2021). Application of agent-based modeling and life cycle sustainability assessment to evaluate biorefinery placement. Biomass and Bioenergy, 144, 105916. https://doi.org/10.1016/j.biombioe.2020.105916

Forest Ownership Patterns in the Western Upper Peninsula of Michigan, USA

Published in Journal of Forestry, 2020

In heavily forested rural areas, tax-incentivization programs are commonly employed to encourage timber production and harvesting activities. Because of growing interest in developing woody-biomass-based biofuels in the Western Upper Peninsula of Michigan, USA, we analyzed property records to determine who the regional actors are along with what role tax-incentivization programs may play. We found that a minority of entities collectively control 77 percent of the land in the region; however, family forest owners collectively own 23 percent of the land. Although tax-incentive programs are commonly used by commercial forests, the requirements of the primary program in Michigan program appear to preclude most family forests in the region. Accordingly, this study suggests that a greater understanding of reluctance of family forests to enroll in secondary programs is needed, or a lowering of forestland requirements to permit more family forests to enroll.

Recommended citation: Zupko, R. (2020). Forest Ownership Patterns in the Western Upper Peninsula of Michigan, USA. Journal of Forestry, 118(5), 466-473. https://doi.org/10.1093/jofore/fvaa027

Agent-Based model to predict the fate of the degradation of organic compounds in the aqueous-phase UV/H₂O₂ advanced oxidation process

Published in Process Safety and Environmental Protection, 2020

Advanced oxidation processes (AOPs) are promising water treatment technologies used to destroy trace organic compounds. Yet, the inability to predict the degradation fate of trace organic compounds due to their diverse chemical structures and potential for transformation byproducts greatly limits AOP effectiveness. Current prediction methods are time consuming and discontinuous because they rely on conventional kinetic models that often require solving ‘stiff’ ordinary differential equations numerically. In this study, we present a novel approach to AOP degradation prediction that uses an agent-based model to represent the chemical entities of individual molecular species and to simulate the movement and reactions of these entities over time in a defined space. Predicted time-dependent concentration profiles of a parent test compound, acetone, and its transformation products in UV/H₂O₂ AOP are shown to be consistent with our experimental observations.

Recommended citation: Zupko, R., Kamath, D., Coscarelli, E., Rouleau, M., & Minakata, D. (2020). Agent-Based model to predict the fate of the degradation of organic compounds in the aqueous-phase UV/H2O2 advanced oxidation process. Process Safety and Environmental Protection, 136, 49-55. https://doi.org/10.1016/j.psep.2020.01.023

Agent-Based Modeling for bioenergy sustainability assessment

Published in Landscape and Urban Planning, 2019

Woody biomass bioenergy is an important renewable alternative to conventional fossil fuels. However, the negative land-use change impacts of biomass harvesting necessary for bioenergy production can potentially outweigh its positive benefits if poorly managed. In this paper, we explain how Agent-Based Modeling (ABM), a form of computer simulation, can be used to conduct a comprehensive bioenergy sustainability assessment to identify possible gains and trade-offs necessary to develop bioenergy in regions with large numbers of private family forest owners or smallholders who own a significant share of available biomass. We discuss how ABM simulation can overcome the barriers of existing sustainability assessment tools and provide a demonstration of the sustainability assessment capabilities of an ABM using a hypothetical case study that explores the introduction of a bioenergy conversion facility in the Western Upper Peninsula of Michigan, United States. We conduct a series of alternative futures scenarios and compare the sustainability outcomes of three alternative policy regimes using voluntary incentive programs to encourage smallholders to harvest biomass.

Recommended citation: Rouleau, M., & Zupko, R. (2019). Agent-based modeling for bioenergy sustainability assessment. Landscape and Urban Planning, 188, 54-63. https://doi.org/10.1016/j.landurbplan.2019.04.019

Life cycle assessment of the production of gasoline and diesel from forest residues using integrated hydropyrolysis and hydroconversion

Published in The International Journal of Life Cycle Assessment, 2019

Purpose: Renewable gasoline and diesel can be produced through integrated hydropyrolysis and hydroconversion (IH2) using renewable feedstocks such as woody biomass from logging residues. This study assesses the potential environmental impacts of IH2 process fuels manufactured in Ontonagon, Michigan, to determine their environmental impacts and if these manufactured fuels will meet Renewable Fuel Standards (RFS) requirements. The energy return on investment (EROI) is also calculated for comparison to other renewable fuels.
Methods: A cradle-to-grave life cycle assessment was conducted using regional forestry, timber harvest, and transportation data from the region. Regional geographic data was used to determine service areas that may provide woody biomass. The service areas were then developed into inventory data based upon the type and distribution of potential woody biomass feedstocks. Survey data from loggers in the region were used to ensure that harvest types were allocated in accordance with regional activity. Remaining inventory items were derived from existing data in the literature or existing life cycle inventory databases. This study uses a functional unit of one megajoule of gasoline or diesel produced using the IH2 process and assessed several environmental indicators as well as EROI.
Results and discussion: Fuels produced generate approximately 88% less greenhouse gas (GHG) emissions compared to petroleum fuels given RFS assumptions. Manufacturing and transportation of feedstocks accounts for 92.19% of energy used in production giving a calculated EROI of 4.19 and 4.31 per kilogram of diesel and gasoline, respectively. Pessimistic estimates of soil organic carbon (SOC) loss result in GHG emissions that are approximately 83% lower. If a 1:0.5 displacement ratio of IH2 fuels is considered, the GHG emissions are about 76% lower without SOC loss and 66% lower with. This study demonstrates that while environmental impacts and EROI are sensitive to site selection and SOC estimates, there is a sufficient GHG emission reduction such that IH2 fuels are capable of meeting regulatory requirements.
Conclusions: Fuels produced at the facility result in a reduction in GHG emissions, but better site selection may result in less fuel being used in transportation. Reducing the quantity of electricity needed in n-th–generation facilities would also reduce environmental impacts while improving the EROI. The energy mix used to supply IH2 facilities should also be considered during the planning process. Finally, future research may be needed to ensure feedstocks recovered from logging operations match expectations.

Recommended citation: Zupko, R. (2019). Life cycle assessment of the production of gasoline and diesel from forest residues using integrated hydropyrolysis and hydroconversion. The International Journal of Life Cycle Assessment, 24(10), 1793-1804. https://doi.org/10.1007/s11367-019-01616-8

ForestSim: Spatially explicit agent-based modeling of non-industrial forest owner policies

Published in SoftwareX, 2019

Woody biomass bioenergy is an important renewable alternative to conventional fossil fuels. However, the negative land-use change impacts of biomass harvesting necessary for bioenergy production can potentially outweigh its positive benefits if poorly managed. In this paper, we explain how Agent-Based Modeling (ABM), a form of computer simulation, can be used to conduct a comprehensive bioenergy sustainability assessment to identify possible gains and trade-offs necessary to develop bioenergy in regions with large numbers of private family forest owners or smallholders who own a significant share of available biomass. We discuss how ABM simulation can overcome the barriers of existing sustainability assessment tools and provide a demonstration of the sustainability assessment capabilities of an ABM using a hypothetical case study that explores the introduction of a bioenergy conversion facility in the Western Upper Peninsula of Michigan, United States. We conduct a series of alternative futures scenarios and compare the sustainability outcomes of three alternative policy regimes using voluntary incentive programs to encourage smallholders to harvest biomass.

Recommended citation: Zupko, R., & Rouleau, M. (2019). ForestSim: Spatially explicit agent-based modeling of non-industrial forest owner policies. SoftwareX, 9, 117-125. https://doi.org/10.1016/j.softx.2019.01.008

Fuzzy decision making in an agent-based model of non-industrial private forest owners

Published in 2017 IEEE Symposium Series on Computational Intelligence (SSCI), 2018

This paper presents the development and application of a fuzzy inference system (FIS) to an agent-based model of non-industrial private forest owner (NIPFO) timber harvesting activity. The FIS inputs and rules are developed based upon survey and literature data on NIPFOs and agents are embedded into a forested landscape similar to real conditions. Model results indicate harvesting patterns similar to what is actually observed. I argue that these encouraging results indicate the technique merits further development.

Recommended citation: Zupko, R. (2017). Fuzzy decision making in an agent-based model of non-industrial private forest owners. In 2017 IEEE Symposium Series on Computational Intelligence (SSCI) (pp. 1-8). IEEE. https://doi.org/10.1109/SSCI.2017.8285222

An Agent-based Model of Voluntary Incentive Programs for Sustainable Biofuel Development

Published in Social Simulation Conference 2016, 2016

Recommended citation: Zupko, R., Ghimre, H., Nouhan, P., & Rouleau, M. (2016, September). An Agent-based Model of Voluntary Incentive Programs for Sustainable Biofuel Development. In Social Simulation Conference 2016 (pp. 1-4). Download Manuscript

Introduction to the IEEE 802.16 Standard: Wireless Broadband Access

Published in The Rivier Academic Journal, 2007

The IEEE 802.16 Standard, first published in 2001, defines a means for wireless broadband access as a replacement for current cable and DSL 'last mile' services to home and business. The adoption of this standard is currently in progress through the use of WiMAX Forum certified networking equipment and widespread adoption should appear over the next few years. This paper provides an overview of the 802.16 standard in regards to frequency bands, the physical layer specification, security sublayer, MAC common part sublayer, and service specific convergence sublayer

Recommended citation: Zupko, R. J. (2007). Introduction to the IEEE 802.16 Standard: Wireless Broadband Access. The Rivier Academic Journal, 3(1). https://www2.rivier.edu/journal/rcoaj-spring-2007/j70-zupko.pdf | Download Manuscript