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All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Fusing time-varying mosquito data and continuous mosquito population dynamics models

Climate change is arguably one of the most pressing issues affecting the world today and requires the fusion of disparate data streams to accurately model its impacts. Mosquito populations respond to temperature and precipitation in a nonlinear way, making predicting climate impacts on mosquito-borne diseases an ongoing challenge. Data-driven approaches for accurately modeling mosquito populations are needed for predicting mosquito-borne disease risk under climate change scenarios. Many current models for disease transmission are continuous and autonomous, while mosquito data is discrete and varies both within and between seasons. This study uses an optimization framework to fit a non-autonomous logistic model with periodic net growth rate and carrying capacity parameters for 15 years of daily mosquito time-series data from the Greater Toronto Area of Canada. The resulting parameters accurately capture the inter-annual and intra-seasonal variability of mosquito populations within a single geographic region, and a variance-based sensitivity analysis highlights the influence each parameter has on the peak magnitude and timing of the mosquito season. This method can easily extend to other geographic regions and be integrated into a larger disease transmission model. This method addresses the ongoing challenges of data and model fusion by serving as a link between discrete time-series data and continuous differential equations for mosquito-borne epidemiology models.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2023

Cognitively defined Alzheimer's dementia subgroups have distinct atrophy patterns

We sought to determine structural magnetic resonance imaging (MRI) characteristics across subgroups defined based on relative cognitive domain impairments using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and to compare cognitively defined to imaging-defined subgroups. We used data from 584 people with Alzheimer's disease (AD) (461 amyloid positive, 123 unknown amyloid status) and 118 amyloid-negative controls. We used voxel-based morphometry to compare gray matter volume (GMV) for each group compared to controls and to AD-Memory. There was pronounced bilateral lower medial temporal lobe atrophy with relative cortical sparing for AD-Memory, lower left hemisphere GMV for AD-Language, anterior lower GMV for AD-Executive, and posterior lower GMV for AD-Visuospatial. Formal asymmetry comparisons showed substantially more asymmetry in the AD-Language group than any other group (p = 1.15 × 10 -10 ). For overlap between imaging-defined and cognitively defined subgroups, AD-Memory matched up with an imaging-defined limbic predominant group. MRI findings differ across cognitively defined AD subgroups.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

A Comparison of Infectious Disease Forecasting Methods across Locations, Diseases, and Time

Accurate infectious disease forecasting can inform efforts to prevent outbreaks and mitigate adverse impacts. This study compares the performance of statistical, machine learning (ML), and deep learning (DL) approaches in forecasting infectious disease incidences across different countries and time intervals. We forecasted three diverse diseases: campylobacteriosis, typhoid, and Q-fever, using a wide variety of features (n = 46) from public datasets, e.g., landscape, climate, and socioeconomic factors. We compared autoregressive statistical models to two tree-based ML models (extreme gradient boosted trees [XGB] and random forest [RF]) and two DL models (multi-layer perceptron and encoder–decoder model). The disease models were trained on data from seven different countries at the region-level between 2009–2017. Forecasting performance of all models was assessed using mean absolute error, root mean square error, and Poisson deviance across Australia, Israel, and the United States for the months of January through August of 2018. The overall model results were compared across diseases as well as various data splits, including country, regions with highest and lowest cases, and the forecasted months out (i.e., nowcasting, short-term, and long-term forecasting). Overall, the XGB models performed the best for all diseases and, in general, tree-based ML models performed the best when looking at data splits. There were a few instances where the statistical or DL models had minutely smaller error metrics for specific subsets of typhoid, which is a disease with very low case counts. Feature importance per disease was measured by using four tree-based ML models (i.e., XGB and RF with and without region name as a feature). The most important feature groups included previous case counts, region name, population counts and density, mortality causes of neonatal to under 5 years of age, sanitation factors, and elevation. This study demonstrates the power of ML approaches to incorporate a wide range of factors to forecast various diseases, regardless of location, more accurately than traditional statistical approaches.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Population-level incidence of human papillomavirus–positive oropharyngeal, cervical, and anal cancers, by smoking status

Abstract We estimated the population-level incidence of human papillomavirus (HPV)–positive oropharyngeal, cervical, and anal cancers by smoking status. We combined HPV DNA genotyping data from the Centers for Disease Control and Prevention’s Cancer Registry Sentinel Surveillance System with data from the Kentucky Cancer Registry and Behavioral Risk Factor Surveillance System across smoking status. During 2004-2005 and 2014-2015 in Kentucky, most cases of oropharyngeal (63.3%), anal (59.7%), and cervical (54.9%) cancer were among individuals who ever smoked. The population-level incidence rate was higher among individuals who ever smoked than among those who never smoked for HPV-positive oropharyngeal (7.8 vs 2.1; adjusted incidence rate ratio = 2.6), cervical (13.7 vs 6.8; adjusted incidence rate ratio = 2.0), and anal (3.9 vs 1.6; adjusted incidence rate ratio = 2.5) cancers. These findings indicate that smoking is associated with increased risk of HPV-positive oropharyngeal, cervical, and anal cancers, and the population-level burden of these cancers is higher among individuals who ever smoked.

Oncology↗
DOE OSTI2023

A scoping review of zoonotic parasites and pathogens associated with abattoirs in Eastern Africa and recommendations for abattoirs as disease surveillance sites

Abattoirs are facilities where livestock are slaughtered and are an important aspect in the food production chain. There are several types of abattoirs, which differ in infrastructure and facilities, sanitation and PPE practices, and adherence to regulations. In each abattoir facility, worker exposure to animals and animal products increases their risk of infection from zoonotic pathogens. Backyard abattoirs and slaughter slabs have the highest risk of pathogen transmission because of substandard hygiene practices and minimal infrastructure. These abattoir conditions can often contribute to environmental contamination and may play a significant role in disease outbreaks within communities. To assess further the risk of disease, we conducted a scoping review of parasites and pathogens among livestock and human workers in abattoirs across 13 Eastern African countries, which are hotspots for zoonoses. Our search results (n = 104 articles) showed the presence of bacteria, viruses, fungi, and macroparasites (nematodes, cestodes, etc.) in cattle, goats, sheep, pigs, camels, and poultry. Most articles reported results from cattle, and the most frequent pathogen detected was Mycobacterium bovis, which causes bovine tuberculosis. Some articles included worker survey and questionnaires that suggested how the use of PPE along with proper worker training and safe animal handling practices could reduce disease risk. Based on these findings, we discuss ways to improve abattoir biosafety and increase biosurveillance for disease control and mitigation. Abattoirs are a ‘catch all’ for pathogens, and by surveying animals at abattoirs, health officials can determine which diseases are prevalent in different regions and which pathogens are most likely transmitted from wildlife to livestock. We suggest a regional approach to biosurveillance, which will improve testing and data gathering for enhanced disease risk mapping and forecasting. Next generation sequencing will be key in identifying a wide range of pathogens, rather than a targeted approach.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

U.S. Department of Energy: National Virtual Biotechnology Laboratory (Technical Report)

With funding from the CARES Act, the U.S Department of Energy (DOE) established the National Virtual Biotechnology Laboratory (NVBL) in March 2020 to address key challenges associated with the COVID-19 crisis. The NVBL brought together the broad scientific and technical expertise and resources of DOE’s 17 national laboratories to help tackle medical supply shortages, discover potential drugs to fight the virus, develop and validate COVID-19 testing methods, model disease spread and impact across the nation, and understand virus transport in buildings and the environment. National laboratory resources leveraged for this effort include a suite of world-leading user facilities broadly available to the research community, such as light and neutron sources, nanoscale science research centers, sequencing and biocharacterization facilities, and high-performance computing facilities. As part of the NVBL framework, DOE rapidly assembled five project teams to (1) identify new targets for medical therapeutics; (2) develop innovations in testing capabilities; (3) provide epidemiological and logistical support; (4) understand viral fate and transport in the environment; and (5) address supply chain bottlenecks by harnessing extensive additive manufacturing capabilities. Each research team was charged with defining high-impact projects that could be completed in a 6-month sprint while coordinating their developments with academia, other government agencies, and the private sector. Within months, NVBL teams used DOE’s high-performance computers and light and neutron sources to identify promising candidates for antibodies and antivirals that universities and drug companies are now evaluating. NVBL researchers also developed new diagnostic targets and sample collection approaches, and supported efforts by the U.S. Food and Drug Administration, Centers for Disease Control and Prevention, and U.S. Department of Defense to establish national guidelines used in administering millions of tests. Researchers used artificial intelligence and high-performance computing to produce near-real-time data analysis to forecast disease transmission, stress on public health infrastructure, and economic impact, which supported decision-makers at the local, state, and national levels. To minimize virus uptake and protect human health, NVBL teams studied how to control indoor virus movement. Researchers also produced innovations in materials and advanced manufacturing that mitigated shortages in test kits and personal protective equipment, creating nearly 1,000 new jobs. Through its NVBL framework, DOE has contributed significantly to the nation’s COVID response, demonstrating in only a few months the critical impact of its national laboratories. NVBL’s accomplishments demonstrate not only the powerful resource represented by DOE’s national laboratories working together to meet national needs, but also the effectiveness of the integrated NVBL framework for rapidly responding to emergencies with research and development solutions. Going forward, the NVBL is poised to apply the unique capabilities and expertise of the national laboratory complex to future national and international emergencies, both natural and engineered. Through this framework, DOE will continue to be an integral component of agency-wide efforts to prepare for and respond to biorisks and other crises. This technical report describes the goals, progress, and results of NVBL’s five project teams—Molecular Design for COVID-19 Therapeutics, COVID-19 Testing, Epidemiological Modeling, Viral Fate and Transport, and Materials and Manufacturing of Critical Supplies—and lists each team’s publications and research output.

42 ENGINEERING↗
DOE OSTI2023

GeoAI for Public Health

Infectious disease spread within the human population can be conceptualized as a complex system composed of individuals who interact and transmit viruses through spatio-temporal processes that manifest across and between scales. The complexity of this system ultimately means that the spread of infectious diseases is difficult to understand, predict, and respond to effectively. Research interest in GeoAI for public health has been fueled by the increased availability of rich data sources such as human mobility data, OpenStreetMap data, contact tracing data, symptomatic online surveys, retail and commerce data, genomics data, and more. This data availability has resulted in a wide variety of data-driven solutions for infectious disease spread prediction which show potential in enhancing our forecasting capabilities. This chapter (1) motivates the need for AI-based solutions in public health by showing the heterogeneity of human behavior related to health, (2) provides a brief survey of current state-of-the-art solutions using AI for infectious disease spread prediction, (3) describes a use-case of using large-scale human mobility data to inform AI models for the prediction of infectious disease spread in a city, and (4) provides future research directions and ideas.

Zufle, Andreas↗
DOE OSTI2021

National Virtual Biotechnology Laboratory: Report on Rapid R&D Solutions to the COVID-19 Crisis

With funding from the CARES Act, the U.S Department of Energy (DOE) established the National Virtual Biotechnology Laboratory (NVBL) in March 2020 to address key challenges associated with the COVID-19 crisis. NVBL brought together the broad scientific and technical expertise and resources of DOE’s 17 national laboratories to help tackle medical supply short ages, discover potential drugs to fight the virus, develop and validate COVID-19 testing methods, model disease spread and impact across the nation, and understand virus transport in buildings and the environment. National laboratory resources leveraged for this effort include a suite of world-leading user facilities broadly available to the research community, such as light and neutron sources, nanoscale science research centers, sequencing and biocharacterization facilities, and high-performance computing facilities. Within months, NVBL teams produced innovations in materials and advanced manufacturing that mitigated shortages in test kits and personal protective equipment (PPE), creating nearly 1,000 new jobs. They used DOE’s high-performance computers and light and neutron sources to identify promising candidates for antibodies and antivirals that universities and drug companies are now evaluating. NVBL researchers also developed new diagnostic targets and sample collection approaches, and supported U.S. Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDC), and U.S. Department of Defense (DoD) efforts to establish national guidelines used in administering millions of tests. Researchers used artificial intelligence and high-performance computing to produce near-real-time data analysis to forecast disease transmission, stress on public health infrastructure, and economic impact, which supported decision-makers at the local, state, and national levels. NVBL teams also studied how to control indoor virus movement to minimize uptake and protect human health. NVBL’s accomplishments demonstrate not only the powerful resource represented by DOE’s national laboratories working together to meet national needs, but also the effectiveness of the integrated NVBL framework for rapidly responding to emergencies with research and development (R&D) solutions. As the fight against COVID continues, sustained efforts are needed to confront this pandemic as well as future threats. Examples include: 1) Establishing “supply chains on demand” to meet emergency production needs by leveraging the materials and manufacturing expertise of DOE national laboratories and developing advances in electronics, sensing, robotics, and automation capabilities; 2) Improving the speed and robustness of drug discovery by integrating experimental platforms with DOE’s computational and experimental user facilities, which provide unique resources to support the discovery of high-potential therapeutic agents; 3) Protecting public, environmental, and animal health by developing new testing protocols and instrumentation adaptable to diverse sample types (both physiological and environmental) to quickly detect a wide range of pathogens and monitor other biorisks; 4) Supporting near-real-time data needs of decision-makers at the local, regional, state, and national levels by advancing data curation, analysis, and modeling using artificial intelligence and new data science tools for managing and evaluating large diverse datasets; 5) Harnessing DOE’s expertise in environmental modeling to design rooms and air handling for offices, classrooms, restaurants, and other structures to minimize biorisk transmissions. Going forward, NVBL is poised to apply the unique capabilities and expertise of the national laboratory complex to future national and international emergencies, both natural and engineered. Through this framework, the Office of Science will continue to be an integral component of agency wide efforts to prepare for and respond to biorisks and other crises.

42 ENGINEERING↗
DOE OSTI2025

GenAI-Based Digital Twins Aided Data Augmentation Increases Accuracy in Real-Time Cokurtosis-Based Anomaly Detection of Wearable Data

Early detection of potential infectious disease outbreaks is crucial for developing effective interventions. In this study, we introduce advanced anomaly detection methods tailored for health datasets collected from wearables, offering insights at both individual and population levels. Leveraging real-world physiological data from wearables, including heart rate and activity, we developed a framework for the early detection of infection in individuals. Despite the availability of data from recent pandemics, substantial gaps remain in data collection, hindering method development. To bridge this gap, we utilized Wasserstein Generative Adversarial Networks (WGANs) to generate realistic synthetic wearable data, augmenting our dataset for training. Subsequently, we use these augmented datasets to implement a cokurtosis-based technique for anomaly detection in multivariate time-series data. Our approach includes a comprehensive assessment of uncertainties in synthetic data compared to the actual data upon which it was modeled, as well as the uncertainty associated with fine-tuning anomaly detection thresholds in physiological measurements. Through our work, we present an enhanced method for early anomaly detection in multivariate datasets, with promising applications in healthcare and beyond. This framework could revolutionize early detection strategies and significantly impact public health response efforts in future pandemics.

Data-Driven Digital Twins↗
DOE OSTI2020

Modelling kidney disease using ontology: insights from the Kidney Precision Medicine Project

An important need exists to better understand and stratify kidney disease according to its underlying pathophysiology in order to develop more precise and effective therapeutic agents. National collaborative efforts such as the Kidney Precision Medicine Project are working towards this goal through the collection and integration of large, disparate clinical, biological and imaging data from patients with kidney disease. Ontologies are powerful tools that facilitate these efforts by enabling researchers to organize and make sense of different data elements and the relationships between them. Ontologies are critical to support the types of big data analysis necessary for kidney precision medicine, where heterogeneous clinical, imaging and biopsy data from diverse sources must be combined to define a patient’s phenotype. Here, the development of two new ontologies — the Kidney Tissue Atlas Ontology and the Ontology of Precision Medicine and Investigation — will support the creation of the Kidney Tissue Atlas, which aims to provide a comprehensive molecular, cellular and anatomical map of the kidney. These ontologies will improve the annotation of kidney-relevant data, and eventually lead to new definitions of kidney disease in support of precision medicine.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Transmission risk of Oropouche fever across the Americas

Abstract Background Vector-borne diseases (VBDs) are important contributors to the global burden of infectious diseases due to their epidemic potential, which can result in significant population and economic impacts. Oropouche fever, caused by Oropouche virus (OROV), is an understudied zoonotic VBD febrile illness reported in Central and South America. The epidemic potential and areas of likely OROV spread remain unexplored, limiting capacities to improve epidemiological surveillance. Methods To better understand the capacity for spread of OROV, we developed spatial epidemiology models using human outbreaks as OROV transmission-locality data, coupled with high-resolution satellite-derived vegetation phenology. Data were integrated using hypervolume modeling to infer likely areas of OROV transmission and emergence across the Americas. Results Models based on one-support vector machine hypervolumes consistently predicted risk areas for OROV transmission across the tropics of Latin America despite the inclusion of different parameters such as different study areas and environmental predictors. Models estimate that up to 5 million people are at risk of exposure to OROV. Nevertheless, the limited epidemiological data available generates uncertainty in projections. For example, some outbreaks have occurred under climatic conditions outside those where most transmission events occur. The distribution models also revealed that landscape variation, expressed as vegetation loss, is linked to OROV outbreaks. Conclusions Hotspots of OROV transmission risk were detected along the tropics of South America. Vegetation loss might be a driver of Oropouche fever emergence. Modeling based on hypervolumes in spatial epidemiology might be considered an exploratory tool for analyzing data-limited emerging infectious diseases for which little understanding exists on their sylvatic cycles. OROV transmission risk maps can be used to improve surveillance, investigate OROV ecology and epidemiology, and inform early detection.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

How robust are estimates of key parameters in standard viral dynamic models?

Mathematical models of viral infection have been developed, fitted to data, and provide insight into disease pathogenesis for multiple agents that cause chronic infection, including HIV, hepatitis C, and B virus. However, for agents that cause acute infections or during the acute stage of agents that cause chronic infections, viral load data are often collected after symptoms develop, usually around or after the peak viral load. Consequently, we frequently lack data in the initial phase of viral growth, i.e., when pre-symptomatic transmission events occur. Missing data may make estimating the time of infection, the infectious period, and parameters in viral dynamic models, such as the cell infection rate, difficult. However, having extra information, such as the average time to peak viral load, may improve the robustness of the estimation. Here, we evaluated the robustness of estimates of key model parameters when viral load data prior to the viral load peak is missing, when we know the values of some parameters and/or the time from infection to peak viral load. Although estimates of the time of infection are sensitive to the quality and amount of available data, particularly pre-peak, other parameters important in understanding disease pathogenesis, such as the loss rate of infected cells, are less sensitive. Viral infectivity and the viral production rate are key parameters affecting the robustness of data fits. Fixing their values to literature values can help estimate the remaining model parameters when pre-peak data is missing or limited. We find a lack of data in the pre-peak growth phase underestimates the time to peak viral load by several days, leading to a shorter predicted growth phase. On the other hand, knowing the time of infection (e.g., from epidemiological data) and fixing it results in good estimates of dynamical parameters even in the absence of early data. While we provide ways to approximate model parameters in the absence of early viral load data, our results also suggest that these data, when available, are needed to estimate model parameters more precisely.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Comparison of Social Media, Syndromic Surveillance, and Microbiologic Acute Respiratory Infection Data: Observational Study

Internet data can be used to improve infectious disease models. However, the representativeness and individual-level validity of internet-derived measures are largely unexplored as this requires ground truth data for study. This study sought to identify relationships between Web-based behaviors and/or conversation topics and health status using a ground truth, survey-based dataset. This study leveraged a unique dataset of self-reported surveys, microbiological laboratory tests, and social media data from the same individuals toward understanding the validity of individual-level constructs pertaining to influenza-like illness in social media data. Logistic regression models were used to identify illness in Twitter posts using user posting behaviors and topic model features extracted from users’ tweets. Of 396 original study participants, only 81 met the inclusion criteria for this study. Of these participants’ tweets, we identified only two instances that were related to health and occurred within 2 weeks (before or after) of a survey indicating symptoms. It was not possible to predict when participants reported symptoms using features derived from topic models (area under the curve [AUC]=0.51; P=.38), though it was possible using behavior features, albeit with a very small effect size (AUC=0.53; P≤.001). Individual symptoms were also generally not predictable either. The study sample and a random sample from Twitter are predictably different on held-out data (AUC=0.67; P≤.001), meaning that the content posted by people who participated in this study was predictably different from that posted by random Twitter users. Individuals in the random sample and the GoViral sample used Twitter with similar frequencies (similar @ mentions, number of tweets, and number of retweets; AUC=0.50; P=.19). To our knowledge, this is the first instance of an attempt to use a ground truth dataset to validate infectious disease observations in social media data. The lack of signal, the lack of predictability among behaviors or topics, and the demonstrated volunteer bias in the study population are important findings for the large and growing body of disease surveillance using internet-sourced data.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Pneumonia After Bacterial or Viral Infection Preceded or Followed by Radiation Exposure: A Reanalysis of Older Radiobiologic Data and Implications for Low-Dose Radiation Therapy for Coronavirus Disease 2019 Pneumonia

Currently, there are about 15 ongoing clinical studies on low dose radiation therapy for Coronavirus Disease 2019 pneumonia. One of the underlying assumptions is that irradiation of 0.5 to 1.5 Gy is effective at ameliorating viral pneumonia. We aimed to reanalyze all available experimental radiobiologic data to assess evidence for such amelioration.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2024

Harmonizing tau positron emission tomography in Alzheimer's disease: The CenTauR scale and the joint propagation model

Abstract INTRODUCTION Tau‐positron emission tomography (PET) outcome data of patients with Alzheimer's disease (AD) cannot currently be meaningfully compared or combined when different tracers are used due to differences in tracer properties, instrumentation, and methods of analysis. METHODS Using head‐to‐head data from five cohorts with tau PET radiotracers designed to target tau deposition in AD, we tested a joint propagation model (JPM) to harmonize quantification (units termed “CenTauR” [CTR]). JPM is a statistical model that simultaneously models the relationships between head‐to‐head and anchor point data. JPM was compared to a linear regression approach analogous to the one used in the amyloid PET Centiloid scale. RESULTS A strong linear relationship was observed between CTR values across brain regions. Using the JPM approach, CTR estimates were similar to, but more accurate than, those derived using the linear regression approach. DISCUSSION Preliminary findings using the JPM support the development and adoption of a universal scale for tau‐PET quantification. Highlights Tested a novel joint propagation model (JPM) to harmonize quantification of tau PET. Units of common scale are termed “CenTauRs”. Tested a Centiloid‐like linear regression approach. Using five cohorts with head‐to‐head tau PET, JPM outperformed linearregressionbased approach. Strong linear relationship was observed between CenTauRs values across brain regions.

Neurosciences & Neurology↗
DOE OSTI2024

Personalized whole-brain neural mass models reveal combined Aβ and tau hyperexcitable influences in Alzheimer's disease.

Neuronal dysfunction and cognitive deterioration in Alzheimer's disease (AD) are likely caused by multiple pathophysiological factors. However, mechanistic evidence in humans remains scarce, requiring improved non-invasive techniques and integrative models. We introduce personalized AD computational models built on whole-brain Wilson-Cowan oscillators and incorporating resting-state functional MRI, amyloid-β (Aβ) and tau-PET from 132 individuals in the AD spectrum to evaluate the direct impact of toxic protein deposition on neuronal activity. This subject-specific approach uncovers key patho-mechanistic interactions, including synergistic Aβ and tau effects on cognitive impairment and neuronal excitability increases with disease progression. The data-derived neuronal excitability values strongly predict clinically relevant AD plasma biomarker concentrations (p-tau217, p-tau231, p-tau181, GFAP) and grey matter atrophy obtained through voxel-based morphometry. Furthermore, reconstructed EEG proxy quantities show the hallmark AD electrophysiological alterations (theta band activity enhancement and alpha reductions) which occur with Aβ-positivity and after limbic tau involvement. Microglial activation influences on neuronal activity are less definitive, potentially due to neuroimaging limitations in mapping neuroprotective vs detrimental activation phenotypes. Mechanistic brain activity models can further clarify intricate neurodegenerative processes and accelerate preventive/treatment interventions.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Evaluation of a visual interpretation method for tau-PET with 18 F-flortaucipir

Introduction: Positron emission tomography targeting tau (tau-PET) is a promising diagnostic tool for the identification of Alzheimer's disease (AD). Currently available data rely on quantitative measures, and a visual interpretation method, critical for clinical translation, is needed. Methods: In this work, we developed a visual interpretation method for 18 F-flortaucipir tau-PET and tested it on 274 individuals (cognitively normal controls, patients with mild cognitive impairment [MCI], AD dementia, and non-AD diagnoses). Two readers interpreted 18 F-flortaucipir PET using two complementary indices: a global visual score and a visual distribution pattern. Results: Global visual scores were reliable, correlated with global cortical 18 F-flortaucipir standardized uptake value ratio (SUVR) and were associated with clinical diagnosis and amyloid status. The AD-like 18 F-flortaucipir pattern had good sensitivity and specificity to identify amyloid-positive patients with AD dementia or MCI. Discussion: This 18 F-flortaucipir visual rating scheme is associated with SUVR quantification, clinical diagnosis, and amyloid status, and constitutes a promising approach to tau measurement in clinical settings.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Foodborne illness outbreaks linked to unpasteurised milk and relationship to changes in state laws – United States, 1998–2018

Consumption of unpasteurised milk in the United States has presented a public health challenge for decades because of the increased risk of pathogen transmission causing illness outbreaks. We analysed Foodborne Disease Outbreak Surveillance System data to characterise unpasteurised milk outbreaks. Using Poisson and negative binomial regression, we compared the number of outbreaks and outbreak-associated illnesses between jurisdictions grouped by legal status of unpasteurised milk sale based on a May 2019 survey of state laws. During 2013–2018, 75 outbreaks with 675 illnesses occurred that were linked to unpasteurised milk; of these, 325 illnesses (48%) were among people aged 0–19 years. Of 74 single-state outbreaks, 58 (78%) occurred in states where the sale of unpasteurised milk was expressly allowed. Compared with jurisdictions where retail sales were prohibited (n = 24), those where sales were expressly allowed (n = 27) were estimated to have 3.2 (95% CI 1.4–7.6) times greater number of outbreaks; of these, jurisdictions where sale was allowed in retail stores (n = 14) had 3.6 (95% CI 1.3–9.6) times greater number of outbreaks compared with those where sale was allowed on-farm only (n = 13). This study supports findings of previously published reports indicating that state laws resulting in increased availability of unpasteurised milk are associated with more outbreak-associated illnesses and outbreaks.

60 APPLIED LIFE SCIENCES↗