The Adverse Outcome Pathway (AOP) framework is a pivotal tool for organizing mechanistic knowledge and linking it to adverse outcomes of regulatory significance. However, the integration of test method information, particularly New Approach Methods (NAMs), within the central repository for AOP knowledge, (the AOP-Wiki), has been suboptimal, limiting the framework's utility for regulatory decision-making. The Methods2AOP collaboration, comprised of various international stakeholders, was established to address this gap and enhance the role of test methods within the AOP framework. This paper reviews their work emphasizing the importance of linking detailed test method information and conceptually proposes how it may be included in the AOP knowledgebase in alignment with existing assay documentation standards and governance frameworks. The Methods2AOP collaboration proposes using ontologies to standardize and structure information, thereby facilitating interoperability, enabling reusability, and establishing clear connections between test methods and Key Events (KEs). A conceptual model is presented to demonstrate qualitative similarities between concepts in key event components and structured methods information. The implementation of Methods2AOP recommendations would increase the clarity and transparency of method descriptions, which could support regulatory acceptance and a wider adoption of NAMs. The broad community of stakeholders impacted by this work stands to benefit from the Methods2AOP recommendations through enhanced regulatory decisions, increased visibility and scientific impact, new market opportunities, and the accelerated adoption of NAMs in regulatory affairs. In summary, the Methods2AOP collaboration presents a comprehensive effort to formally standardize the integration of test methods into the AOP framework, thereby fostering a more robust, and transparent system that aligns with the goals of the scientific and regulatory communities.
Two solutions containing ~500 mg/L of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) were atomized at two post-flame locations within a natural gas-fired pilot-scale combustor with peak temperatures of ~860 °C and ~750 °C. The thermal destruction of PFOS and PFOA and the formation of fluorocarbon products of incomplete combustion (PICs) were analyzed using EPA Other Test Method (OTM)-45, a prepublication version of EPA OTM-50, an activated carbon-based thermal desorption (TD) tube gas chromatography/mass spectrometry (GC/MS) method, and two real-time methods including iodine-adduct chemical ionization mass spectrometry (CIMS) and Fourier transform infrared spectrometry (FTIR). Destruction efficiencies (DEs) determined for PFOS by OTM-45 and for PFOA by both OTM-45 and CIMS, were >99.99% for both peak injection temperatures. OTM-45 and CIMS confirmed the presence of several perfluorocarboxylic acids (PFCAs) as PICs. These PFCAs included trifluoroacetic acid (TFA) and perfluoropropionic acid (PFPrA) for both solutions and included the formation of PFOA from PFOS and similarly perfluoroheptanoic acid (PFHpA) from PFOA. PFCA concentrations and the relative amounts of PFOA and PFHpA increased at the lower temperature. OTM-50 and the TD tube analysis identified numerous fluorocarbon PICs including 1H-pefluoroalkanes, and perfluoroalkanes such as trifluoromethane (CHF3) and hexafluoroethane (C2F6).
Thawing permafrost will significantly impact regulatory activities in Alaska that are conducted by the U.S. Environmental Protection Agency (EPA) to protect human health and the environment. Many of those activities are in vulnerable rural lands predominantly occupied by Alaska Natives. Temperatures in Alaska-the largest and northernmost of the 50 states-are increasing disproportionately relative to the global average and at a markedly higher rate than in any other state in the Nation. Most land and surface waters in Alaska are underlaid by permafrost (or perennially frozen ground), which stabilizes infrastructure, serves community needs, and shapes ecosystems with unique environmental characteristics. The Fourth National Climate Assessment estimated that 16-24% of near-surface Alaskan permafrost could disappear by the end of this century. Permafrost thaw not only compromises critical infrastructure used in daily life (e.g., buildings, roads, and pipelines), but also alters movement of hazardous substances within the surrounding environment. Changes to permafrost characteristics and extent may release contaminants through multiple mechanisms which can pollute air, soil, and water, with unintended consequences to subsistence activities and the livelihood of local communities. This paper summarizes information gathered from semi-formal interviews conducted with EPA regulatory staff during late 2022 to glean the breadth of activities that would be affected by permafrost thaw, tabulate available data sources, and identify data and knowledge gaps. This information can be used to influence monitoring activities and future research that can inform EPA regulatory activities affected by permafrost thaw in Alaska.
Introduction and Objective: Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of cirrhosis. NIS2+™ is a novel blood-based diagnostic test developed to identify “at-risk” MASH (steatohepatitis with significant fibrosis stage ≥F2) that combines miR-34a-5p (microRNA linked to altered lipid metabolism) and YKL-40 (biomarker of fibrosis). Our aim was to assess the prevalence of “at-risk” MASH by NIS2+™ in unselected people from primary care or endocrine outpatient university clinics. Methods: We recruited 687 participants and assessed for “at-risk” MASH by NIS2+™ (defined as NIS2+™ ≥0.68). We measured by transient elastography (Fibroscan®) steatosis (CAP≥274 dB/m) and fibrosis (Liver Stiffness Measurement [VCTE-LSM]≥7.0 kPa). A subset underwent magnetic resonance (MR) iron-corrected T1 mapping for MASH disease activity (cT1) and MR-elastography (MRE) for fibrosis (n=51). Results: Overall, 44% had T2D (28% with obesity); 25% obesity alone, without T2D; and 31% neither. “At-risk” MASH by NIS2+™ was observed in up to 20% individuals with obesity and T2D, 13% with obesity only and 3% in those without obesity or T2DM (all p<0.001 vs. obesity and/or T2D). People with “at-risk” MASH vs. low-risk MASH by NIS2+™ had more often steatosis (80% vs 46%), fibrosis (30% vs 5%), AST≥40 IU/L (39% vs. 1%), ALT≥40 IU/L (46% vs. 4%), hepatic IR (HOMA-IR≥3.0: 66% vs. 32%) and adipose tissue IR (adipo-IR≥2.0: 80% vs 62%) (all p<0.01). NIS2+™ correlated with CK-18, a marker of hepatocyte apoptosis (r=0.49, p<0.001), with cT1 (r=0.44, p=0.002) and liver fibrosis by VCTE-LSM (r=0.29, p<0.001) or MRE (r=0.28, p=0.049). Conclusion: “At-risk” MASH with severe steatohepatitis and significant fibrosis (stage ≥F2) is common in unselected patients with obesity and/or T2D (~20%) in outpatient primary care and endocrinology clinics. More awareness and early risk-stratification will help identify people in need of early intervention and intensive multidisciplinary care. S. Kalavalapalli: None. E. Godinez Leiva: None. A. Ortiz Rocha: None. N. Cuervo-Pardo: None. K.Y. Chun: Employee; LabCorp. T.R. Prezant: None. M.A. Connelly: Employee; LabCorp. Stock/Shareholder; LabCorp. A. Sharma: None. D. Barb: Other Relationship; Inventiva Pharma, Boehringer-Ingelheim. K. Cusi: Research Support; Boehringer-Ingelheim, Echosens, Inventiva, Perspectum Ltd, LabCorp. Consultant; Arrowhead Pharmaceuticals, Inc, AstraZeneca, TERNS Pharmaceuticals, 89bio, Inc, Boehringer-Ingelheim, Eli Lilly and Company, Novo Nordisk A/S, Sagimet Biosciences. NIH/NIDDK (R01DK120331); PI: Kenneth Cusi.
Urban areas and their surroundings feature unique, horizontally inhomogeneous spatial distributions of land use and land cover, leading to urban heat islands (UHIs) for both air and land surface temperature that complicate the estimation of urban sensible heat flux. The urban dispersion option in AERMOD, the American Meteorological Society (AMS)/Environmental Protection Agency (EPA) Regulatory Model, incorporates this effect at night through a “convective like boundary layer” that modifies the single column meteorology based on a population number representative of the urban area. The model produces positive nighttime sensible heat flux values that often significantly overestimate observed values from the literature. This study re-examines the formulation of the AERMOD urban option assumptions, methodology, and original evaluation against a field study of a power plant in Indianapolis. We investigate replacing the population-based parameterizations of urban–surrounding temperature differences (ΔT) with observations of remotely sensed land surface temperature (LST) data from the Advanced Baseline Imager on the GOES-16/R/East geostationary satellite. We generated a monthly averaged, hourly, wind direction-dependent, clear sky land surface urban heat island ΔT database for 480 continental United States (CONUS) urban areas, as defined by the 2010 US Census. These ΔT values are used to advise city-specific horizontal advection corrections to sensible heat flux estimates that are neglected from simple energy balance models. The four cities of Cleveland, Amarillo, Atlanta, and Baltimore are highlighted, showing that the AERMOD predicted nighttime ΔT values are 794%, 416%, 1048%, and 758% higher, respectively, than the GOES-16 observations. These overestimated ΔT values in AERMOD lead to nighttime sensible heat flux values > 100 W/m2 that rival daytime values. However, using the GOES-16 observations as horizontal advection corrections to sensible heat flux results in trends that match the expected neutral to slightly positive nighttime values from observations recorded in the literature. The annual nighttime average in 2021 was −0.8 W/m2, 8.6 W/m2, 3.0 W/m2, and 3.1 W/m2 in Cleveland, Amarillo, Atlanta, and Baltimore, respectively, using this approach. Finally, reviewing the initial evaluation with the Indianapolis database against independent studies from the literature suggest that the AERMOD urban option inadvertently implements an urban heat island modeling approach to account for what was a low-level jet during the field study.
