• Adjusting statistical benchmark risk analysis to account for non-spatial autocorrelation, with application to natural hazard risk assessment

      Liu, Jingyu; Piegorsch, Walter W.; Schissler, A. Grant; McCaster, Rachel R.; Cutter, Susan L.; Interdisciplinary Program in Statistics & Data Science, University of Arizona; BIO5 Institute, University of Arizona; Department of Mathematics, University of Arizona (Taylor and Francis Ltd., 2021-04-01)
      We develop and study a quantitative, interdisciplinary strategy for conducting statistical risk analyses within the ‘benchmark risk’ paradigm of contemporary risk assessment when potential autocorrelation exists among sample units. We use the methodology to explore information on vulnerability to natural hazards across 3108 counties in the conterminous 48 US states, applying a place-based resilience index to an existing knowledgebase of hazardous incidents and related human casualties. An extension of a centered autologistic regression model is applied to relate local, county-level vulnerability to hazardous outcomes. Adjustments for autocorrelation embedded in the resiliency information are applied via a novel, non-spatial neighborhood structure. Statistical risk-benchmarking techniques are then incorporated into the modeling framework, wherein levels of high and low vulnerability to hazards are identified. © 2021 Informa UK Limited, trading as Taylor & Francis Group.
    • Applying planetary mapping methods to submarine environments: onshore-offshore geomorphology of Christiana-Santorini-Kolumbo Volcanic Group, Greece

      Huff, A.E.; Nomikou, P.; Thompson, L.A.; Hooft, E.E.E.; Walker, I.J.; Arizona Geological Survey, University of Arizona (Taylor and Francis Ltd., 2021)
      Geologic maps are foundational products for natural hazard assessments but developing them for submarine areas is challenging due to a lack of physical access to the study area. In response, submarine geomorphologic maps are used to provide geologic context and spatial information on landforms and related geo-hazards for risk management. These maps are generated from remotely sensed data, e.g. digital elevation models (DEMs), which introduce unique hurdles to submarine mapping. To address this issue, we produced a workflow for applying planetary geologic mapping methods to submarine data. Using this, we created an onshore-offshore geomorphologic map of the Christiana-Santorini-Kolumbo Volcanic Group, Greece. This product can be used to enhance hazard assessments on Santorini, which is a tourist hot-spot at high risk for volcanically- and seismically-induced hazards. We present this workflow as a tool for generating uniform geomorphologic map products that will aid natural hazard assessments of submarine environments. © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of Journal of Maps.
    • Collagen/kerateine multi-protein hydrogels as a thermally stable extracellular matrix for 3D in vitro models

      Zuniga, K.; Gadde, M.; Scheftel, J.; Senecal, K.; Cressman, E.; Van Dyke, M.; Rylander, M.N.; College of Biomedical Engineering, The University of Arizona (Taylor and Francis Ltd., 2021)
      Objective: To determine whether the addition of kerateine (reduced keratin) in rat tail collagen type I hydrogels increases thermal stability and changes material properties and supports cell growth for use in cellular hyperthermia studies for tumor treatment. Methods: Collagen type I extracted from rat tail tendon was combined with kerateine extracted from human hair fibers. Thermal, mechanical, and biocompatibility properties and cell behavior was assessed and compared to 100% collagen type I hydrogels to demonstrate their utility as a tissue model for 3D in vitro testing. Results: A combination (i.e., containing both collagen ‘C/KNT’) hydrogel was more thermally stable than pure collagen hydrogels and resisted thermal degradation when incubated at a hyperthermic temperature of 47°C for heating durations up to 60 min with a higher melting temperature measured by DSC. An increase in the storage modulus was only observed with an increased collagen concentration rather than an increased KTN concentration; however, a change in ECM structure was observed with greater fiber alignment and width with an increase in KTN concentration. The C/KTN hydrogels, specifically 50/50 C/KTN hydrogels, also supported the growth and of fibroblasts and MDA-MB-231 breast cancer cells similar to those seeded in 100% collagen hydrogels. Conclusion: This multi-protein C/KTN hydrogel shows promise for future studies involving thermal stress studies without compromising the 3D ECM environment or cell growth. © 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.
    • Death by hand sanitizer: syndemic methanol poisoning in the age of COVID-19

      Holzman, Sarah Denise; Larsen, Jaiva; Kaur, Ramandeep; Smelski, Geoffrey; Dudley, Steven; Shirazi, Farshad Mazda; Arizona Poison and Drug Information Center, University of Arizona College of Pharmacy; Department of Emergency Medicine, University of Arizona College of Medicine; Department of Medical Pharmacology, University of Arizona College of Medicine; Department of Pharmacy Practice and Science, University of Arizona College of Pharmacy (Taylor and Francis Ltd., 2021-03-23)
      Background: The advent of COVID-19 increased attention to hand hygiene in prevention of disease transmission. To meet the increased demand for hand sanitizer during the pandemic, the US FDA issued an Emergency Use Authorization allowing new manufacturers and importers to enter the market. Some of the newly introduced hand sanitizer products contained methanol in lieu of ethanol or isopropanol. We describe five patients with fatal methanol poisoning resulting from hand sanitizers improperly containing methanol. Case summary: Comparing a 5-month period from 2019 to the same time frame in 2020, the Arizona Poison and Drug Information Center has seen an increase of 124% in exposures to hand sanitizer. Of these cases, 28% involved methanol-contaminated hand sanitizer. Five of these patients died from methanol poisoning. All five cases had similar clinical features with severe high anion gap metabolic acidosis and, in four patients, elevated osmolal gap. Methanol concentrations were consistently very elevated, but these results were not available before the patients succumbed. Four of the patients received fomepizole and adjunctive care. Two patients received emergency extracorporeal therapy. All five died despite maximal treatment efforts. Conclusion: During the pandemic in 2020, there was a proliferation of alcohol-based hand sanitizers which contained methanol. Exposure to these products, which failed to meet regulatory standards, led to increased harm and death. Challenges to treatment of methanol poisoning, especially in rural areas, include lack of access to timely laboratory measurement of methanol concentrations and lack of available emergency hemodialysis without transfer of the patient. © 2021 Informa UK Limited, trading as Taylor & Francis Group.
    • Eigenvector-spatial localisation

      Harty, T.; Morzfeld, M.; Snyder, C.; Program in Applied Mathematics, University of Arizona (Taylor and Francis Ltd., 2021)
      We present a new multiscale covariance localisation method for ensemble data assimilation that is based on the estimation of eigenvectors and subsequent projections, together with traditional spatial localisation applied with a range of localisation lengths. In short, we estimate the leading, large-scale eigenvectors from the sample covariance matrix obtained by spatially smoothing the ensemble (treating small scales as noise) and then localise the resulting sample covariances with a large length scale. After removing the projection of each ensemble member onto the leading eigenvectors, the process may be repeated using less smoothing and tighter localizations or, in a final step, using the resulting, residual ensemble and tight localisation to represent covariances in the remaining subspace. We illustrate the use of the new multiscale localisation method in simple numerical examples and in cycling data assimilation experiments with the Lorenz Model III. We also compare the proposed new method to existing multiscale localisation and to single-scale localisation. © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
    • Feasibility of community health workers as teleaudiology patient-site facilitators: a multilevel training study

      Coco, Laura; Piper, Rosie; Marrone, Nicole; College of Science, Department of Speech, Language, and Hearing Sciences, University of Arizona (Taylor and Francis Ltd., 2021-01-06)
      Objective: We evaluated the feasibility of a multi-level teleaudiology patient-site facilitator training program for Community Health Workers (CHWs) at a partnering health centre in southern Arizona. Design: Three levels were offered: Introductory, with basic information on hearing loss and teleaudiology; Intermediate, on technology, team roles, and access issues; and Facilitator, on further knowledge and hands-on skills to serve as patient-site facilitators in synchronous hearing aid service delivery. Six domains of feasibility were addressed using a mixed-methods design. Quantitative data included survey responses and observation of hands-on skills. Qualitative data included field notes from group discussion and open-ended survey questions, and were analysed using CHW core competencies. Study sample: Twelve CHWs participated in the introductory training, ten moved on to intermediate, and three continued to the facilitator. Results: Quantitative outcomes indicated that the trainings were feasible according to each of the six domains. CHWs in the facilitator training passed the practical hands-on skill assessment. Qualitative analyses revealed CHWs comments addressed eight of the ten possible CHW core competencies, and focussed on service coordination/navigation, and capacity building. Conclusions: Teleaudiology trainings for CHWs were feasible, increasing service capacity for a potential pathway to improve access to hearing health care in low-resource areas. © 2020 British Society of Audiology, International Society of Audiology, and Nordic Audiological Society.
    • Have CD19-directed immunotherapy and haploidentical hematopoietic cell transplantation transformed pediatric B-cell acute lymphoblastic leukemia into a chronic disease?

      Pariury, H.; Truscott, L.; Katsanis, E.; Department of Pediatrics, University of Arizona; The University of Arizona Cancer Center; Banner University Medical Center; Department of Immunobiology, University of Arizona; Department of Medicine, University of Arizona; Department of Pathology, University of Arizona (Taylor and Francis Ltd., 2021)
      The treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL) has undergone several recent advancements, leading to an increased amount of treatment options for relapsed patients. The development of immunotherapies such as anti-CD19 chimeric antigen receptor(CAR) T cells and bispecific T-cell engagers has given clinicians therapeutic options with less expected toxicity when compared to standard re-induction chemotherapy. This is especially beneficial in patients with toxicities from their prior treatment. Along with this, the emergence of haploidentical hematopoietic cell transplantation (HCT) has increased opportunity for patients to receive HCT who may not have had an available matched donor. We present four patients who have received all of these therapies in different combinations to treat multiple relapses. Because of the success of achieving remission as well as decreasing toxicity, the patients are alive and well up to 15 y after the original B-ALL diagnosis, rendering this as a chronic disease for them. © 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.
    • Mandible morphology as a tool to investigate origin, adaptation and stress in invasive alien species: first insights into Callosciurus erythraeus (Rodentia: Sciuridae) in Europe

      Mazzamuto, M.V.; Su, H.-J.; Guidarelli, G.; Preatoni, D.; Russo, L.F.; Loy, A.; Martinoli, A.; School of Natural Resources and Environment, University of Arizona (Taylor and Francis Ltd., 2021)
      When an alien species is introduced in a new area, the new population may be genetically and phenotypically different from the parent population because of the population bottleneck, increased inbreeding rate and adaptation to the new environment. In this study we investigated the variation in shape and size of the mandible among and within three populations of the invasive Pallas’s squirrel introduced in Italy, Belgium and France. Significant differences in both size and shape of the mandible were found among all population pairs, with France being the most distinct. French squirrels showed a larger and slenderer mandible with a broad angular process, a restricted condyle, and a backward-oriented coronoid process. The Italian and the Belgian population also differed significantly but to a lesser extent, the Italian squirrels having a lower coronoid process, a broader angular apophysis, and a restricted condyle. Size explained 15% of the total shape variation, but the slope of allometric trajectories did not reveal any significant difference among populations. A significantly high fluctuating and directional asymmetries were found respectively in the French and the Italian squirrels. Results are discussed in terms of different selective pressures in the invaded areas and possible effects of developmental instability. © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
    • Medicaid and Medicare Part B spending on immunomodulators and biosimilars

      Thompson, Alyssa M; Atluri, Swetha; Price, Kyla N; Hsiao, Jennifer L; Shi, Vivian Y; College of Medicine, University of Arizona (Taylor and Francis Ltd., 2021-02-18)
      Introduction: Prices for immunomodulators used in dermatological conditions are rising in the United States. While Medicare Part-D solely covers medication costs, Medicare Part-B covers outpatient infusion and injection costs given by medical professionals. We aim to analyze recent trends in Medicare Part-B spending on immunomodulators and their biosimilars used in the treatment of common chronic inflammatory dermatoses. Methods: The 2012–2018 Medicare Part-B spending data on immunomodulators commonly used for dermatologic conditions were extracted from the Centers for Medicare and Medicaid Services database. Inflation was adjusted to reflect 2012-dollar amounts using the Consumer Price Index. Results: Medicare Part-B spending has increased by 27.5% from 2012 to 2018 ($2.5B, $3.2B). Average annual total spending (AATS) is greatest for rituximab ($1,522,757,520), and average annual spending per maintenance dose (AASPMD) is greatest for ustekinumab-90 mg ($12,976). The percent change in AASPMD increased for all immunomodulators with Etanercept-50 mg having the greatest percent change (+64.6%, +$285.70). Infliximab had a greater AATS and AASPMD than its biosimilars. Discussion: Medicare Part-B spending is often overlooked but plays a big role in federal healthcare spending. Exploring the strategic use of less expensive biosimilars could help mitigate spending.
    • Parameter estimation from ICC curves

      Lega, J.; Department of Mathematics, University of Arizona (Taylor and Francis Ltd., 2021)
      Incidence vs. Cumulative Cases (ICC) curves are introduced and shown to provide a simple framework for parameter identification in the case of the most elementary epidemiological model, consisting of susceptible, infected, and removed compartments. This novel methodology is used to estimate the basic reproduction ratio of recent outbreaks, including those associated with the ongoing COVID-19 pandemic. © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
    • Probabilities of designed locations of ceremonial foci: the Chaco Meridian, temple IV at Tikal, and a large-scale sacred Adena river landscape

      Doxtater, Dennis; School of Architecture, College of Architecture, Planning and Landscape Architecture, University of Arizona (Taylor and Francis Ltd., 2021-04-06)
      Considering that prehistoric cultures may have had the socio-religious need and technical ability to create accurate geometric patterns across a large landscape, limited ethnographic and archaeologic evidence are reviewed. Simple but accurate land surveying is discussed. Since any set of existing sites at larger scales coincidentally creates accurate three-point alignments and right-angles, the critical research problem attempts to distinguish designed from random geometry. Unpublished patterns involving great kivas in Chaco Canyon and Temple IV at Tikal are tested for probabilities of design. The more expansive third test considers the location of 26 prominent Adena mounds in relation to 32 river confluence points and four highest mountains in a geographic area some 900 × 1200 km, just slightly larger than a Chacoan world. In 14 test boxes modeling the locations of the 26 mounds, 1000 sets of random points replace equal numbers in each box. Each set is searched for numbers of three-point alignments and ninety-degree angles at or under 0.10º accuracy. Chaco and Tikal tests show a strong likelihood of design at these sites; in the Adena, data indicate a high probability that some number of existing patterns were intentionally surveyed. © 2021 Informa UK Limited, trading as Taylor & Francis Group.
    • Rational design of a deuterium-containing M2-S31N channel blocker UAWJ280 with in vivo antiviral efficacy against both oseltamivir sensitive and -resistant influenza A viruses

      Cáceres, C.J.; Hu, Y.; Cárdenas-García, S.; Wu, X.; Tan, H.; Carnaccini, S.; Gay, L.C.; Geiger, G.; Ma, C.; Zhang, Q.-Y.; et al. (Taylor and Francis Ltd., 2021)
      Seasonal influenza A virus (IAV) infections are among the most important global health problems. FDA-approved antiviral therapies against IAV include neuraminidase inhibitors, M2 inhibitors, and polymerase inhibitor baloxavir. Resistance against adamantanes (amantadine and rimantadine) is widespread as virtually all IAV strains currently circulating in the human population are resistant to adamantanes through the acquisition of the S31N mutation. The neuraminidase inhibitor-resistant strains also contain the M2-S31N mutant, suggesting M2-S31N is a high-profile antiviral drug target. Here we report the development of a novel deuterium-containing M2-S31N inhibitor UAWJ280. UAWJ280 had broad-spectrum antiviral activity against both oseltamivir sensitive and -resistant influenza A strains and had a synergistic antiviral effect in combination with oseltamivir in cell culture. In vivo pharmacokinetic (PK) studies demonstrated that UAWJ280 had favourable PK properties. The in vivo mouse model study showed that UAWJ280 was effective alone or in combination with oseltamivir in improving clinical signs and survival after lethal challenge with an oseltamivir sensitive IAV H1N1 strain. Furthermore, UAWJ280 was also able to ameliorate clinical signs and increase survival when mice were challenged with an oseltamivir-resistant IAV H1N1 strain. In conclusion, we show for the first time that the M2-S31N channel blocker UAWJ280 has in vivo antiviral efficacy in mice that are infected with either oseltamivir sensitive or -resistant IAVs, and it has a synergistic antiviral effect with oseltamivir. © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
    • Shrub influence on soil carbon and nitrogen in a semi-arid grassland is mediated by precipitation and largely insensitive to livestock grazing

      Throop, Heather L.; Munson, Seth; Hornslein, Nicole; McClaran, Mitchel P.; School of Natural Resources and the Environment, University of Arizona (Taylor and Francis Ltd., 2021-07-22)
      Dryland (arid and semi-arid) ecosystems globally provide more than half of livestock production and store roughly one-third of soil organic carbon (SOC). Biogeochemical pools are changing due to shrub encroachment, livestock grazing, and climate change. We assessed how vegetation microsite, grazing, and precipitation interacted to affect SOC and total nitrogen (TN) at a site with long-term grazing manipulations and well-described patterns of shrub encroachment across elevation and mean annual precipitation (MAP) gradients. We analyzed SOC and TN in the context of vegetation cover at ungrazed locations within livestock exclosures, high-intensity grazing locations near water sources, and moderate-intensity grazing locations away from water. SOC was enhanced by MAP (p < 0.0001), but grazing intensity had little effect regardless of MAP (p = 0.12). Shrubs enhanced SOC (300–1279 g C m−2) and TN (27–122 g N m−2), except at high MAP where the contribution or stabilization of shrub inputs relative to grassland inputs was likely diminished. Cover of perennial herbaceous plants and litter were significant predictors of SOC (r 2 = 0.63 and 0.34, respectively) and TN (r 2 = 0.64 and 0.30, respectively). Our results suggest that continued shrub encroachment in drylands can increase SOC storage when grass production remains high, although this response may saturate with higher MAP. In contrast, grazing–at least at the intensities of our sites–has a lesser effect. These effects underscore the need to understand how future climate and grazing may interact to influence dryland biogeochemical cycling. © 2021 Taylor & Francis Group, LLC.
    • The in vitro antiviral activity of lactoferrin against common human coronaviruses and SARS-CoV-2 is mediated by targeting the heparan sulfate co-receptor

      Hu, Y.; Meng, X.; Zhang, F.; Xiang, Y.; Wang, J.; Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona (Taylor and Francis Ltd., 2021)
      Coronavirus disease 2019 (COVID-19) is an ongoing pandemic that lacks effective therapeutic interventions. SARS-CoV-2 infects ACE2-expressing cells and gains cell entry through either direct plasma membrane fusion or endocytosis. Recent studies have shown that in addition to ACE2, heparan sulfate proteoglycans (HSPGs) also play an important role in SARS-CoV-2 cell attachment by serving as an attachment factor. Binding of viral spike protein to HSPGs leads to the enrichment of local concentration for the subsequent specific binding with ACE2. We therefore hypothesize that blocking the interactions between viral spike protein and the HSPGs will lead to inhibition of viral replication. In this study, we report our findings of the broad-spectrum antiviral activity and the mechanism of action of lactoferrin (LF) against multiple common human coronaviruses as well as SARS-CoV-2. Our study has shown that LF has broad-spectrum antiviral activity against SARS-CoV-2, HCoV-OC43, HCoV-NL63, and HCoV-229E in cell culture, and bovine lactoferrin (BLF) is more potent than human lactoferrin. Mechanistic studies revealed that BLF binds to HSPGs, thereby blocking viral attachment to the host cell. The antiviral activity of BLF can be antagonized by the HSPG mimetic heparin. Combination therapy experiment showed that the antiviral activity of LF is synergistic with remdesivir in cell culture. Molecular modelling suggests that the N-terminal positively charged region in BLF (residues 17-41) confers the binding to HSPGs. Overall, LF appears to be a promising drug candidate for COVID-19 that warrants further investigation. © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd.
    • The liver X receptor agonist LXR 623 restricts flavivirus replication

      Mlera, L.; Offerdahl, D.K.; Dorward, D.W.; Carmody, A.; Chiramel, A.I.; Best, S.M.; Bloom, M.E.; BIO5 Institute, University of Arizona (Taylor and Francis Ltd., 2021)
      The vector-borne flaviviruses (VBFVs) are well known for causing great misery and death in humans worldwide. The VBFVs include those transmitted by mosquitos, such as Zika virus (ZIKV), dengue virus; and those transmitted by ticks including the tick-borne flavivirus serocomplex and Powassan virus (POWV). Two of our recent reports showed that intracranial POWV infection in the reservoir host, Peromyscus leucopus, was restricted and caused no overt clinical disease. Several modes of analyses suggested activation of the LXR pathway. Activation of the LXR pathway leads to increased efflux of cholesterol from cells and consequent disturbances in membrane biogenesis. Because VBFV replication is dependent on membrane biogenesis, we evaluated the effect of an LXR agonist (LXR623) on POWV and ZIKV infection and observed that the compound impaired permissive replication of both viruses in a human neuroblastoma SK-N-SH cell line. The LXR agonist resulted in failure of the viruses to induce ER expansion and elaborate vesicle formation, suggesting that the efflux of cholesterol was part of the antiviral mechanism. We also observed that the LXR agonist contributed to the mechanism of virus suppression by increased expression of mRNAs encoding for the antiviral cytokines CXCL10, RANTES and IFN1β. In sharp contrast, a LXR antagonist (GSK2033) had no significant effect on VBFV replication. We conclude that LXR623 impairs flavivirus replication by stimulating cellular antiviral factors. © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd.
    • Use of Crotalidae equine immune F(ab’)2 antivenom for treatment of an Agkistrodon envenomation

      Wilson, B. Z.; Larsen, J.; Smelski, G.; Dudley, S.; Shirazi, F. M.; Arizona Poison and Drug Information Center, University of Arizona (Taylor and Francis Ltd., 2021-03-11)
      Introduction: Anavip (F(ab’)2AV) is a lyophilized F(ab’)2 immunoglobulin fragment derived from horses immunized with venom from Bothrops asper and Crotalus durissus. It was approved by the FDA in 2015 for treatment of North American rattlesnake envenomation but not for Agkistrodon envenomation. Published data regarding the efficacy and safety of Anavip in treating Agkistrodon envenomations is limited. We present a case of a patient treated with Anavip after confirmed Agkistrodon laticinctus envenomation. Case details: A 77 year-old man was bitten on his fifth finger by a captive A. laticinctus. He was taken to a local emergency department where he received a 10 vial initial dose of F(ab’)2AV for pain and swelling and was transferred. At the receiving facility, his pain had improved and his swelling had not progressed. Over the next 30 h, his platelets declined to 132,000/mm3 and he received an additional 4 vials of F(ab’)2AV. The remainder of his course was unremarkable with complete recovery by 3 months. Discussion: This case provides an additional published datapoint on the use of this F(ab’)2AV in the treatment of envenomation by Agkistrodon. © 2021 Informa UK Limited, trading as Taylor & Francis Group.
    • Using global Bayesian optimization in ensemble data assimilation: parameter estimation, tuning localization and inflation, or all of the above

      Lunderman, S.; Morzfeld, M.; Posselt, D.J.; Department of Mathematics, University of Arizona (Taylor and Francis Ltd., 2021)
      Global Bayesian optimization (GBO) is a derivative-free optimization method that is used widely in the tech-industry to optimize objective functions that are expensive to evaluate, numerically or otherwise. We discuss the use of GBO in ensemble data assimilation (DA), where the goal is to update the state of a numerical model in view of noisy observations. Specifically, we consider three tasks: (i) the estimation of model parameters; (ii) the tuning of localization and inflation in ensemble DA; (iii) doing both, i.e. estimating model parameters while simultaneously tuning the localization and inflation of the ensemble DA. For all three tasks, the GBO works ‘offline’, i.e. a set of ‘training’ observations are used within GBO to determine appropriate model or localization/inflation parameters, which are subsequently deployed within an ensemble DA system. Because of the offline nature of the technique, GBO can easily be combined with existing DA systems and it can effectively decouple (nearly) linear/Gaussian aspects of a problem from highly nonlinear/non-Gaussian ones. We illustrate the use of GBO in simple numerical experiments with the classical Lorenz problems. Our main goals are to introduce GBO in the context of ensemble DA and to spark an interest in GBO and its uses for streamlining important tasks in ensemble DA. © Tellus A: 2021. © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.