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At least 181 records · Page 10
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Budget Constrained Machine Learning for Early Prediction of Adverse Outcomes for COVID-19 Patients

Background: Machine learning (ML) based risk stratification models of Electronic Health records (EHR) data may help to optimize treatment of COVID-19 patients, but are often limited by their lack of clinical interpretability and cost of laboratory tests. We develop a ML based tool for predicting adverse outcomes based on EHR data to optimize clinical utility under a given cost structure. This cohort study was performed using deidentified EHR data from COVID-19 patients from ProMedica Healthcare in northwest Ohio and southeastern Michigan. Methods: We tested performance of various ML approaches for predicting either increasing ventilatory support or mortality and the set of model features under a budget constraint was optimized via exhaustive search across all combinations of features. Results: The optimal sets of features for predicting ventilation under any budget constraint included demographics and comorbidities (DCM), basic metabolic panel (BMP), D-dimer, lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), CRP, brain natriuretic peptide (BNP), and procalcitonin and for mortality included DCM, BMP, complete blood count, D-dimer, LDH, CRP, BNP, procalcitonin and ferritin. Conclusions: This study presents a quick, accurate and cost-effective method to evaluate risk of deterioration for patients with SARS-CoV-2 infection at the time of clinical evaluation.

Cadena Pico, JoseE.↗
DOE OSTI2023

Swift and extensive Omicron outbreak in China after sudden exit from ‘zero-COVID’ policy

In late 2022, China transitioned from a strict ‘zero-COVID’ policy to rapidly abandoning nearly all interventions and data reporting. This raised great concern about the presumably-rapid but unreported spread of the SARS-CoV-2 Omicron variant in a very large population of very low pre-existing immunity. By modeling a combination of case count and survey data, we show that Omicron spread extremely rapidly, at a rate of 0.42/day (95% credibility interval: [0.35, 0.51]/day), translating to an epidemic doubling time of 1.6 days ([1.6, 2.0] days) after the full exit from zero-COVID on Dec. 7, 2022. Consequently, we estimate that the vast majority of the population (97% [95%, 99%], sensitivity analysis lower limit of 90%) was infected during December, with the nation-wide epidemic peaking on Dec. 23. Overall, our results highlight the extremely high transmissibility of the variant and the importance of proper design of intervention exit strategies to avoid large infection waves.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2023

Electronic Nose Development and Preliminary Human Breath Testing for Rapid, Non-Invasive COVID-19 Detection

We adapted an existing, spaceflight-proven, robust “electronic nose” (E-Nose) that uses an array of electrical resistivity-based nanosensors mimicking aspects of mammalian olfaction to conduct on-site, rapid screening for COVID-19 infection by measuring the pattern of sensor responses to volatile organic compounds (VOCs) in exhaled human breath. We built and tested multiple copies of a hand-held prototype E-Nose sensor system, composed of 64 chemically sensitive nanomaterial sensing elements tailored to COVID-19 VOC detection; data acquisition electronics; a smart tablet with software (App) for sensor control, data acquisition and display; and a sampling fixture to capture exhaled breath samples and deliver them to the sensor array inside the E-Nose. The sensing elements detect the combination of VOCs typical in breath at parts-per-billion (ppb) levels, with repeatability of 0.02% and reproducibility of 1.2%; the measurement electronics in the E-Nose provide measurement accuracy and signal-to-noise ratios comparable to benchtop instrumentation. Preliminary clinical testing at Stanford Medicine with 63 participants, their COVID-19-positive or COVID-19-negative status determined by concomitant RT-PCR, discriminated between these two categories of human breath with a 79% correct identification rate using “leave-one-out” training-and-analysis methods. Analyzing the E-Nose response in conjunction with body temperature and other non-invasive symptom screening using advanced machine learning methods, with a much larger database of responses from a wider swath of the population, is expected to provide more accurate on-the-spot answers. Additional clinical testing, design refinement, and a mass manufacturing approach are the main steps toward deploying this technology to rapidly screen for active infection in clinics and hospitals, public and commercial venues, or at home.

COVID-19↗
DOE OSTI2024

Quantifying the basic reproduction number and underestimated fraction of Mpox cases worldwide at the onset of the outbreak

In 2022, there was a global resurgence of mpox, with different clinical-epidemiological features compared with previous outbreaks. Sexual contact was hypothesized as the primary transmission route, and the community of men having sex with men (MSM) was disproportionately affected. Because of the stigma associated with sexually transmitted infections, the real burden of mpox could be masked. We quantified the basic reproduction number (R 0 ) and the underestimated fraction of mpox cases in 16 countries, from the onset of the outbreak until early September 2022, using Bayesian inference and a compartmentalized, risk-structured (high-/low-risk populations) and two-route (sexual/non-sexual transmission) mathematical model. Machine learning (ML) was harnessed to identify underestimation determinants. Estimated R 0 ranged between 1.37 (Canada) and 3.68 (Germany). The underestimation rates for the high- and low-risk populations varied between 25–93% and 65–85%, respectively. The estimated total number of mpox cases, relative to the reported cases, is highest in Colombia (3.60) and lowest in Canada (1.08). In the ML analysis, two clusters of countries could be identified, differing in terms of attitudes towards the 2SLGBTQIAP+ community and the importance of religion. Given the substantial mpox underestimation, surveillance should be enhanced, and country-specific campaigns against the stigmatization of MSM should be organized, leveraging community-based interventions.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Complex decay dynamics of HIV virions, intact and defective proviruses, and 2LTR circles following initiation of antiretroviral therapy

In persons living with HIV-1 (PLWH) who start antiretroviral therapy (ART), plasma virus decays in a biphasic fashion to below the detection limit. The first phase reflects the short half-life (<1 d) of cells that produce most of the plasma virus. The second phase represents the slower turnover (t 1/2 = 14 d) of another infected cell population, whose identity is unclear. Using the intact proviral DNA assay (IPDA) to distinguish intact and defective proviruses, we analyzed viral decay in 17 PLWH initiating ART. Circulating CD4 + T cells with intact proviruses include few of the rapidly decaying first-phase cells. Instead, this population initially decays more slowly (t 1/2 = 12.9 d) in a process that largely represents death or exit from the circulation rather than transition to latency. This more protracted decay potentially allows for immune selection. After ~3 mo, the decay slope changes, and CD4 + T cells with intact proviruses decay with a half-life of 19 mo, which is still shorter than that of the latently infected cells that persist on long-term ART. Two-long-terminal repeat (2LTR) circles decay with fast and slow phases paralleling intact proviruses, a finding that precludes their use as a simple marker of ongoing viral replication. Proviruses with defects at the 5' or 3' end of the genome show equivalent monophasic decay at rates that vary among individuals. Understanding these complex early decay processes is important for correct use of reservoir assays and may provide insights into properties of surviving cells that can constitute the stable latent reservoir.

2LTR circles↗
NASA NTRS2016

Mapping Past, Present, and Future Climatic Suitability for Invasive Aedes Aegypti and Aedes Albopictus in the United States: A Process-Based Modeling Approach Using CMIP5 Downscaled Climate Scenarios

The ongoing spread of the mosquitoes, Aedes aegypti and Aedes albopictus, in the continental United States leaves new areas at risk for local transmission of dengue, chikungunya, and Zika viruses. All three viruses have caused major disease outbreaks in the Americas with infected travelers returning regularly to the U.S. The expanding range of these mosquitoes raises questions about whether recent spread has been enabled by climate change or other anthropogenic influences. In this analysis, we used downscaled climate scenarios from the NASA Earth Exchange Global Daily Downscaled Projections (NEX GDDP) dataset to model Ae. aegypti and Ae. albopictus population growth rates across the United States. We used a stage-structured matrix population model to understand past and present climatic suitability for these vectors, and to project future suitability under CMIP5 climate change scenarios. Our results indicate that much of the southern U.S. is suitable for both Ae. aegypti and Ae. albopictus year-round. In addition, a large proportion of the U.S. is seasonally suitable for mosquito population growth, creating the potential for periodic incursions into new areas. Changes in climatic suitability in recent decades for Ae. aegypti and Ae. albopictus have occurred already in many regions of the U.S., and model projections of future climate suggest that climate change will continue to reshape the range of Ae. aegypti and Ae. albopictus in the U.S., and potentially the risk of the viruses they transmit.

process-based modeling↗
DOE OSTI2025

Uncovering heterogeneous intercommunity disease transmission from neutral allele frequency time series

The COVID-19 pandemic has underscored the need for accurate epidemic forecasting to predict pathogen spread, evolution, and evaluate intervention strategies. Forecast reliability hinges on detailed knowledge of disease transmission across population segments, which may be inferred from contact surveys or mobility data. However, these indirect approaches make it difficult to estimate rare transmissions between socially or geographically distant communities. We show that the steep ramp-up of genome sequencing surveillance during the pandemic can be leveraged to directly identify transmission patterns between geographically defined communities. Our approach uses a hidden Markov model to infer the fraction of infections a community imports from others based on how rapidly allele frequencies in the focal community converge to those in the donor communities. Applying this method to SARS-CoV-2 sequencing data from England and the United States, we uncover networks of intercommunity transmission that reflect geographical relationships while exposing significant long-range interactions. The scaling of importation rate with distance is consistent across both countries, yet weaker than expected based on mobility data, highlighting limitations of indirect inference. We show that transmission patterns can change between waves of variants of concern and analyze how the inferred heterogeneity in intercommunity transmission impacts evolutionary forecasts. While applied here to geographically defined communities, our approach could be applied to those defined by other traits (e.g., age, socioeconomic status), provided time-series data can be stratified accordingly. Overall, our study highlights population genomic time series data as a crucial record of epidemiological interactions, which can be deciphered using tree-free inference methods.

Okada, Takashi [Department of Physics; University ↗
DOE OSTI2023

Development of a colloidal gold immunochromatographic assay strip using monoclonal antibody for rapid detection of porcine deltacoronavirus

Porcine deltacoronavirus (PDCoV) cause diarrhea and dehydration in newborn piglets and has the potential for cross-species transmission. Rapid and early diagnosis is important for preventing and controlling infectious disease. In this study, two monoclonal antibodies (mAbs) were generated, which could specifically recognize recombinant PDCoV nucleocapsid (rPDCoV-N) protein. A colloidal gold immunochromatographic assay (GICA) strip using these mAbs was developed to detect PDCoV antigens within 15 min. Results showed that the detection limit of the GICA strip developed in this study was 10 3 TCID 50 /ml for the suspension of virus-infected cell culture and 0.125 μg/ml for rPDCoV-N protein, respectively. Besides, the GICA strip showed high specificity with no cross-reactivity with other porcine pathogenic viruses. Three hundred and twenty-five fecal samples were detected for PDCoV using the GICA strip and reverse transcription-quantitative real-time PCR (RT-qPCR). The coincidence rate of the GICA strip and RT-qPCR was 96.9%. The GICA strip had a diagnostic sensitivity of 88.9% and diagnostic specificity of 98.5%. The specific and efficient detection by the strip provides a convenient, rapid, easy to use and valuable diagnostic tool for PDCoV under laboratory and field conditions.

Wang, Wei↗
DOE OSTI2021

Agent-based Disease Surveillance and Transmission Model

The SARS-CoV-2 pandemic has driven a need for models that can predict transmission among populations and test the effectiveness of proposed interventions to control it such as testing, quarantining, vaccinations, and nonpharmaceutical interventions. Some questions of interest include:1. How rapidly will the virus spread if no action is taken? 2. How frequently should people be tested and quarantined if necessary? 3. Should unvaccinated persons be tested more frequently than the vaccinated? 4. If test results are delayed, how will that affect the spread? 5. How do test false negative rates affect the overall efficacy of testing programs? 6. How do constraints on testing resources impact the overall efficacy of testing programs? 7. How does the patient’s failure to recognize COVID symptoms and quarantine affect the spread? 8. What level of vaccination coverage is needed to suppress the epidemic? 9. What is the risk of a large outbreak (probability exceeding x infections)? 10. What is the cost effectiveness of interventions (dollars per avoided infection)? This report describes the structure of a discrete event simulation model that provides actionable information to address these questions. Parameter inputs and results of analyses have been reported in briefings provided to LLNL management and are not discussed here.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

SARS-CoV-2 Infection-Associated Aortic Thrombosis Treated with Oral Factor Xa Inhibition

Coronavirus disease 2019 (COVID-19) is an acute complex systemic disorder caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).While SARS-CoV-2 is known to cause significant pulmonary disease, various extrapulmonary manifestations of COVID-19 have also been reported. Growing evidence suggests that COVID-19 is associated with coagulopathy leading to micro and macrovascular complications. Although in patients with COVID-19, venous thromboembolic events are more frequent, arterial thrombosis also occurs at an increased rate. These often lead to acute life-threatening ischemia, which requires urgent diagnosis and treatment. We present case reports of two patients with an abnormal thrombus formation in the thoracic aorta who recently overcame COVID-19, which led to systemic embolism and splenic infarction. Ambulatory oral factor Xa inhibitor therapy led to aortic thrombosis resolution in both patients.

Strýčková, Alena↗
DOE OSTI2023

Transient pattern formation in an active matter contact poisoning model

Abstract One of the most notable features in repulsive particle based active matter systems is motility-induced-phase separation (MIPS) where a dense, often crystalline phase and low density fluid coexist. Most active matter studies involve time-dependent activity; however, there are many active systems where individual particles transition from living or moving to dead or nonmotile due to lack of fuel, infection, or poisoning. Here we consider an active matter particle system at densities where MIPS does not occur. When we add a small number of infected particles that can poison other particles, rendering them nonmotile, we find a rich variety of time dependent pattern formation, including MIPS, a wetting phase, and a fragmented state formed when mobile particles plow through a nonmotile packing. We map the patterns as a function of time scaled by epidemic duration, and show that the pattern formation is robust for a wide range of poisoning rates and activity levels. We also show that pattern formation does not occur in a random death model, but requires the promotion of nucleation by contact poisoning. Our results should be relevant to biological and active matter systems where there is some form of poisoning, death, or transition to nonmotility.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2026

Soil viral production count, respiration, and amplicon data

This study aimed to quantify rates of viral production in aridisol soil under conditions as close to natural field soil as possible given the perturbations necessary to manipulate viral abundances. Viruses were removed from soil, then added back to virus-depleted soil to control the initial viral abundances at either 100% (field_abund) or 10% (reduced_abund) of measured field viral abundance to generate treatments with field-relevant and reduced viral infection pressure, respectively. Replicates of batch incubation jars were harvested every 8 hours for 48 hours to enumerate bacteria and viruses by microscopy (n=5) and profile bacterial community composition by 16S rRNA amplicon sequencing (n=3).

Zimmerman, Amy [Pacific Northwest National Laborat↗
DOE OSTI2024

Antimicrobial mechanisms of g‐C 3 N 4 @ ZnO against oomycetes Phytophthora capsici: from its metabolism, membrane structures and growth

Abstract BACKGROUND Phytophthora capsici , a refractory and model oomycete plant pathogen, especially threatens multiple vegetable crops. A limited number of chemical pesticides play a vital role in controlling oomycete plant diseases. However, this approach often leads to excessive use of chemical agent, exacerbates environmental issues and more and more drug‐resistant strains of oomycete. Therefore, it is imperative to devise innovative solutions that can effectively address the infection of oomycete while maintaining high levels of environmental sustainability and low toxicity. RESULTS In this study, g‐C 3 N 4 @ZnO heterostructure was synthesized and characterized. The g‐C 3 N 4 @ZnO showed higher toxicity on Phytophthora capsici than graphitic carbon nitride (g‐C 3 N 4 ) nanosheets and zinc oxide (ZnO) nanoparticles in vitro and in vivo . Except the hyphal growth of Phytophthora capsici , their germination rate of spores, sporangium formation and number of spores were all suppressed by g‐C 3 N 4 @ZnO heterostructure. Furthermore, we found that this g‐C 3 N 4 @ZnO heterostructure has higher photocatalytic activity under visible light, which potentially enhanced the reactive oxygen species (ROS) mediated stress on Phytophthora capsici . Ultrastructural morphology, global changes of gene expression and weighted gene co‐expression network analysis all supported that the anti‐oomycete activity of g‐C 3 N 4 @ZnO was manifested in the destruction of membrane system and inhibition of multiple metabolisms of Phytophthora capsici under visible irradiation, which also could be attributed to the ROS and zinc ion (Zn 2+ ) mediated stress. CONCLUSION This works offers a novel oomycete disease management strategy by using g‐C 3 N 4 @ZnO, which were attributed to the ROS stress, destruction of membrane system and inhibition of multiple metabolisms. © 2023 Society of Chemical Industry.

Cai, Lin↗
DOE OSTI2025

When to vaccinate for seasonal influenza: check the peak forecast

Background Seasonal influenza infects 5-20% of people every year in the United States, resulting in hospitalizations, deaths, and adverse economic impacts. To mitigate these impacts, influenza vaccines are developed and distributed annually; however, growing evidence suggests that vaccine effectiveness (VE) wanes over the course of a flu season. Delaying influenza vaccination for older adults has attracted attention as a potential public health strategy. However, given the uncertainties in seasonal peak, vaccine effectiveness, and waning rates, postponing vaccination could also lead to increased morbidity, motivating an evaluation of a range of potential scenarios. The aim of this study was to investigate favorable age group-specific vaccination schedules that could lead to the greatest disease burden reduction. Methods We systematically investigated a broad range of vaccination start times for five age groups under six combinations of initial effectiveness and waning rates, based on influenza cases and vaccine uptake data from 10 influenza seasons. We defined the most favorable vaccination schedule as the one that resulted in the greatest reduction in disease burden. Results In scenarios with fast waning, all age groups benefit from delaying vaccination regardless of initial VE and peak timing. In scenarios with slower waning, results are mixed. For the ≥65 group, high initial VE and slow waning suggests that in early-peaking seasons, early vaccination most effectively reduces disease burden, while in late-peaking seasons delaying vaccination is most effective. For the ≥65 group in medium and low initial VE, and slow waning scenarios, delaying vaccination appears to prevent the greatest number of cases, regardless of whether the season peaks early or late. Conclusion The most favorable vaccination schedule is sensitive to changes in initial VE, waning rate, and peak timing. Given estimates of these quantities from statistical and immunological models and observations, our methods can inform vaccination recommendations in order to most effectively reduce the annual disease burden caused by seasonal influenza. Specifically, accurate peak timing forecasts for the upcoming season have the potential to guide decisions on when to vaccinate.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Lab Home Testing of Residential Isolation Space Control to Minimize Infectious Disease Transmission in Existing Single-Family Homes

Existing evidence strongly suggests that viral infectious diseases can be transmitted via an airborne route across distances in indoor environments. Accordingly, the risk of airborne transmission within homes should be managed. The public health emergency associated with SARS-CoV-2 makes controlling airborne transmission of respired viruses in indoor environments critical, especially in poorly ventilated indoor environments. The effectiveness of engineering interventions requiring minor efforts that create a negative-pressure isolation zone (IZ) for a contagious person has yet to be tested for existing residential homes. To mitigate the risk of airborne virus transmission and maximize health protection for the population in existing single-family homes, the relative effectiveness of several control strategies are investigated in this report. While very high-efficiency MERV filtration, high ventilation rates, and other controls can help be effective, most occupants are not likely to have the time or means for advanced measures found in hospitals. This project focused on testing relatively simple efforts that utilize existing or easy to acquire materials and simple processes.

30 DIRECT ENERGY CONVERSION↗
DOE OSTI2020

Anti‐adhesive effects of sialic acid and Lactobacillus plantarum on Staphylococcus aureus in vitro

Abstract Staphylococcus aureus (S. aureus) is a common food‐borne pathogen that causes severe diseases after adhesion to epithelial cells. Lactobacillus inhibits pathogenic bacterial adhesion and infection. In addition, sialic acid (SA) is widely known for its beneficial biological functions. A new way of reducing the occurrence of diseases and curbing the overuse of antibiotics is ingesting prebiotics and probiotics that regulate the intestinal flora. In this study, we first evaluated the anti‐adhesive effects of several strains of Lactobacillus on S. aureus . The study revealed that the S. aureus adhesion was inhibited by all the strains of Lactobacillus . Besides, the rate of inhibition by L. plantarum Z‐4 was significantly higher than other Lactobacillus species . We then investigated the effects of different SA concentrations (40, 100, 150, 200, and 260 μg/ml) on the growth and adhesion characteristics of L. plantarum and S. aureus . The results showed that SA influences bacterial adhesion by regulating the bacteria's growth characteristics. Finally, the effects of SA combined with Lactobacillus on the adhesion of S. aureus were assessed by competition, exclusion and displacement methods. SA with a concentration of 260 μg/mL combined with L. plantarum had the highest inhibition effect on the competition assays. In addition, the expression of S. aureus adhesion‐related genes was reduced. This provides a new perspective on the application of SA and/or L. plantarum and its potential to resist adhesion of S. aureus .

Lu, Yingying↗
DOE OSTI2021

Fitness cost of vancomycin-resistant Enterococcus faecium plasmids associated with hospital infection outbreaks

Abstract Background Vancomycin resistance is mostly associated with Enterococcus faecium due to Tn1546-vanA located on narrow- and broad-host plasmids of various families. This study’s aim was to analyse the effects of acquiring Tn1546-carrying plasmids with proven epidemicity in different bacterial host backgrounds. Methods Widespread Tn1546-carrying plasmids of different families RepA_N (n = 5), Inc18 (n = 4) and/or pHTβ (n = 1), and prototype plasmids RepA_N (pRUM) and Inc18 (pRE25, pIP501) were analysed. Plasmid transferability and fitness cost were assessed using E. faecium (GE1, 64/3) and Enterococcus faecalis (JH2-2/FA202/UV202) recipient strains. Growth curves (Bioscreen C) and Relative Growth Rates were obtained in the presence/absence of vancomycin. Plasmid stability was analysed (300 generations). WGS (Illumina-MiSeq) of non-evolved and evolved strains (GE1/64/3 transconjugants, n = 49) was performed. SNP calling (Breseq software) of non-evolved strains was used for comparison. Results All plasmids were successfully transferred to different E. faecium clonal backgrounds. Most Tn1546-carrying plasmids and Inc18 and RepA_N prototypes reduced host fitness (–2% to 18%) while the cost of Tn1546 expression varied according to the Tn1546-variant and the recipient strain (9%–49%). Stability of Tn1546-carrying plasmids was documented in all cases, often with loss of phenotypic resistance and/or partial plasmid deletions. SNPs and/or indels associated with essential bacterial functions were observed on the chromosome of evolved strains, some of them linked to increased fitness. Conclusions The stability of E. faecium Tn1546-carrying plasmids in the absence of selective pressure and the high intra-species conjugation rates might explain the persistence of vancomycin resistance in E. faecium populations despite the significant burden they might impose on bacterial host strains.

Tedim, Ana P.↗
DOE OSTI2022

Transmission history of SARS-CoV-2 in humans and white-tailed deer

The emergence of a novel pathogen in a susceptible population can cause rapid spread of infection. High prevalence of SARS-CoV-2 infection in white-tailed deer ( Odocoileus virginianus ) has been reported in multiple locations, likely resulting from several human-to-deer spillover events followed by deer-to-deer transmission. Knowledge of the risk and direction of SARS-CoV-2 transmission between humans and potential reservoir hosts is essential for effective disease control and prioritisation of interventions. Using genomic data, we reconstruct the transmission history of SARS-CoV-2 in humans and deer, estimate the case finding rate and attempt to infer relative rates of transmission between species. We found no evidence of direct or indirect transmission from deer to human. However, with an estimated case finding rate of only 4.2%, spillback to humans cannot be ruled out. The extensive transmission of SARS-CoV-2 within deer populations and the large number of unsampled cases highlights the need for active surveillance at the human–animal interface.

60 APPLIED LIFE SCIENCES↗