A bicarbonate-rich liquid condensed phase in non-saturated solutions in the absence of divalent cations.

Bicarbonate (HCO3 -) and sodium (Na+)-containing solutions contain droplets of a separate, bicarbonate-rich liquid condensed phase (LCP) that have higher concentrations of HCO3 - relative to the bulk solution in which they reside. The existence and composition of the LCP droplets has been investigated by nanoparticle tracking analysis, nuclear magnetic resonance spectroscopy, refractive index measurements and X-ray pair distribution function analysis. The bicarbonate-rich LCP species is a previously unaccounted-for, ionic phenomenon which occurs even in solutions with solely monovalent cations. Its existence requires re-evaluation of models used to describe and model aqueous solution physicochemistry, especially those used to describe and model carbonate mineral formation.

Influence of Divalent Cation Inhibition and Dissolved Organic Matter Enhancement on Phenol Oxidation Kinetics by Manganese Oxides.

Manganese oxides can oxidize organic compounds, such as phenols, and may potentially be used in passive water treatment applications. However, the impact of common water constituents, including cations and dissolved organic matter (DOM), on this reaction is poorly understood. For example, the presence of DOM can increase or decrease phenol oxidation rates with manganese oxides. Furthermore, the interactions of DOM and cations and their impact on the phenol oxidation rates have not been examined. Therefore, we investigated the oxidation kinetics of six phenolic contaminants with acid birnessite in ten whole water samples. The oxidation rate constants of 4-chlorophenol, 4-tert-octylphenol, 4-bromophenol, and phenol consistently decreased in all waters relative to buffered ultrapure water, whereas the oxidation rate of bisphenol A and triclosan increased by up to 260% in some waters. Linear regression analyses and targeted experiments demonstrated that the inhibition of phenol oxidation is largely determined by cations. Furthermore, quencher experiments indicated that radical-mediated interactions from oxidized DOM contributed to enhanced oxidation of bisphenol A. The variable changes between compounds and water samples demonstrate the challenge of accurately predicting contaminant transformation rates in environmentally relevant systems based on experiments conducted in the absence of natural water constituents.

Medicare price negotiation and pharmaceutical innovation following the Inflation Reduction Act.

The Inflation Reduction Act (IRA) requires Medicare to negotiate lower prices for some medicines with high Medicare spending. Using historical data from public and proprietary sources to apply the IRA's negotiation criteria retrospectively, we identify all drugs that met the eligibility criteria from 2012 to 2021 to classify drugs that would have had a negotiated price in effect in 2022 and to calculate associated decreases in industry revenues. Our results suggest that the IRA's reduction in overall industry revenue will be modest, will not affect most top-selling drugs and will not likely result in large-scale defunding of research and development. Changes in the net present value of drug-development projects will be concentrated in medicines where Medicare is a notable purchaser and where the ratio between expected revenue and development costs was only marginally positive before the IRA. Policymakers considering narrowing or expanding the scope of Medicare negotiation should carefully consider the tradeoffs across medicines with diverse characteristics.

Cost of Exempting Sole Orphan Drugs From Medicare Negotiation.

Importance: The Inflation Reduction Act (IRA) requires Medicare to negotiate prices for some high-spending drugs but exempts drugs approved solely for the treatment of a single rare disease. Objective: To estimate Medicare spending and global revenues for drugs that might have been exempt from negotiation from 2012 to 2021. Design, Setting, and Participants: This cross-sectional study analyzed drugs that met the IRA threshold for price negotiation (Medicare spending >$200 million/y) in any year from 2012 to 2021 and had an Orphan Drug Act designation. We stratified drugs into 4 mutually exclusive categories: approved for a single rare disease (sole orphan), approved for multiple rare diseases (multiorphan), initially approved for a rare disease and subsequently approved for a nonrare disease (orphan first), and initially approved for a nonrare disease and subsequently approved for a rare disease (non-orphan first). Outcomes: The primary outcomes were the number of sole orphan drugs, estimated Medicare spending on those drugs from 2012 to 2021, and global revenue since launch. Results: Among 282 drugs, 95 (34%) were approved to treat at least 1 rare disease, including 25 sole orphan drugs (26%), 20 multiorphan drugs (21%), 13 orphan first drugs (14%), and 37 non-orphan first drugs (39%). From 2012 to 2021, Medicare spending on sole orphan drugs increased from $3.4 billion to $10.0 billion. Each year, a median (IQR) of $2.5 ($1.9-$2.6) billion in Medicare spending would have been excluded from price negotiation because of the sole orphan exemption. The cumulative global revenue of the median (IQR) sole orphan drug was $11 ($6.6-$19.2) billion. Conclusions and Relevance: The sole orphan exemption will exclude billions of dollars of Medicare drug spending from price negotiation. The high level of global revenues achieved by these drugs, however, suggests that special exemption is unnecessary for them to achieve financial success. Congress could consider removing the sole orphan exemption to obtain additional savings for patients and taxpayers and to eliminate any potential disincentive for developing additional indications for these drugs.

Elevated Radium Activity in a Hydrocarbon-Contaminated Aquifer.

Hydrocarbon spills that reach the subsurface can modify aquifer geochemical conditions. Biogeochemical zones typically form proximal to the source zone that include iron (Fe(III)) and manganese (Mn(III/IV)) (hydr)oxide reduction, with potential to release associated geogenic contaminants to groundwater. Here, multi-level monitoring systems are used to investigate radium (226Ra, 228Ra) activities in an aquifer contaminated with a mixture of chlorinated solvents, ketones, and aromatics occurring as a dense non-aqueous phase liquid in the source zone. 226Ra activities are up to 10 times higher than background 60 m downgradient from the source zone, where pH is lower, total dissolved solid concentrations are higher, and conditions are methanogenic. Correlations indicate that Fe and Mn (hydr)oxide reduction and sorption site competition are likely responsible for elevated Ra activities within the dissolved phase plume. 226Ra activities return to background within the Fe(III)/SO42--reducing zone 600 m downgradient from the source, near the middle of the dissolved phase plume. Geochemical models indicate that sorption to secondary phases (e.g., clays) is important in sequestering Ra within the plume. Although maximum Ra activities within the plume are well below the U.S. drinking water standard, elevated activities compared to background emphasize the importance of investigating Ra and other trace elements at hydrocarbon-impacted sites.

Aqueous Co removal by mycogenic Mn oxides from simulated mining wastewaters.

Naturally occurring manganese (Mn) oxide minerals often form by microbial Mn(II) oxidation, resulting in nanocrystalline Mn(III/IV) oxide phases with high reactivity that can influence the uptake and release of many metals (e.g., Ni, Cu, Co, and Zn). During formation, the structure and composition of biogenic Mn oxides can be altered in the presence of other metals, which in turn affects the minerals' ability to bind these metals. These processes are further influenced by the chemistry of the aqueous environment and the type and physiology of microorganisms involved. Conditions extending to environments that typify mining and industrial wastewaters (e.g., increased salt content, low nutrient, and high metal concentrations) have not been well investigated thus limiting the understanding of metal interactions with biogenic Mn oxides. By integrating geochemistry, microscopic, and spectroscopic techniques, we examined the capacity of Mn oxides produced by the Mn(II)-oxidizing Ascomycete fungus Periconia sp. SMF1 isolated from the Minnesota Soudan Mine to remove the metal co-contaminant Co(II) from synthetic waters that are representative of mining wastewaters currently undergoing remediation efforts. We compared two different applied remediation strategies under the same conditions: coprecipitation of Co with mycogenic Mn oxides versus adsorption of Co with pre-formed fungal Mn oxides. Co(II) was effectively removed from solution by fungal Mn oxides through two different mechanisms: incorporation into, and adsorption onto, Mn oxides. These mechanisms were similar for both remediation strategies, indicating the general effectiveness of Co(II) removal by these oxides. The mycogenic Mn oxides were primarily a nanoparticulate, poorly-crystalline birnessite-like phases with slight differences depending on the chemical conditions during formation. The relatively fast and complete removal of aqueous Co(II) during biomineralization as well as the subsequent structural incorporation of Co into the Mn oxide structure illustrated a sustainable cycle capable of continuously remediating Co(II) from metal-polluted environments.

A Regional Approach to Hospital-Based Violence Intervention Programs Through LOV.

CONTEXT: Community violence is an underaddressed public health threat. Hospital-based violence intervention programs (HVIPs) have been used to address the root causes of violence and prevent reinjury. OBJECTIVE: In this article, we describe the methodology of the St Louis Region-wide HVIP, Life Outside Violence (LOV) program, and provide preliminary process outcomes. DESIGN: Life Outside Violence mentors intervene following a violent injury to decrease risk of subsequent victimization and achieve goals unique to each participant by providing therapeutic counseling and case management services to patients and their families. PARTICIPANTS AND SETTING: Eligible patients are victims of violent injury between the ages of 8 and 24 years, who are residents of St Louis, Missouri, and present for care at a LOV partner adult or pediatric level I trauma hospital. INTERVENTION: Enrolled participants receive program services for 6 to 12 months and complete an individual treatment plan. MAIN OUTCOME MEASURES: In this article, we report LOV operational methodology, as well as process metrics, including program enrollment, graduation, and qualitative data on program implementation. RESULTS: From August 15, 2018, through April 30, 2022, 1750 LOV-eligible violently injured patients presented to a partner hospital, 349 were approached for program enrollment, and 206 consented to enroll in the program. During this pilot phase, 91 participants graduated from the LOV program and have process output data available for analysis. CONCLUSIONS: Life Outside Violence has been implemented into clinical practice as the first HVIP to influence across an entire region through partnership with multiple university and hospital systems. It is our hope that methods shared in this article will serve as a primer for organizations hoping to implement and expand HVIPs to interrupt community violence at the regional level.

Investigation of ICP-MS/MS for total sulfur quantification in freshwater dissolved organic matter.

Sulfur-containing functional groups in dissolved organic matter (DOM) interact with trace metals, which in turn affects trace metal mobility and bioavailability in aquatic environments. Typical methods for identification and quantification of sulfur in DOM are costly, complex, and time intensive. Triple quadrupole inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) is capable of part per billion-level sulfur quantification in environmental samples and is a more accessible analytical technique compared with other available methods. This study is the first published investigation of ICP-MS/MS for the direct quantification of sulfur in freshwater DOM. Sulfur (32 S) detection occurs at a mass-to-charge ratio of 48 as 32 S16 O+ after removal of interferences and reaction with oxygen gas. We compare three commonly used DOM preparation methods to assess variability among replicate samples. Preparation of freshwater DOM samples by solid phase extraction followed by evaporation overnight and dissolution in 2% nitric acid results in the most accurate quantification of sulfur. Analysis of sulfur in Suwannee River Fulvic Acid standard serves as method validation, measuring a carbon-normalized sulfur concentration that is ∼20% higher than previously reported methods. We apply the ICP-MS/MS analysis method to determine sulfur concentrations in DOM from nine lakes in the northern Midwest. Carbon-normalized sulfur concentrations in the selected lakes are in general agreement with previously reported percentages of sulfur-containing formulas in DOM found by Fourier transform-ion cyclotron resonance-mass spectroscopy.

Selective Reactivity and Oxidation of Dissolved Organic Matter by Manganese Oxides.

Dissolved organic matter (DOM) varies widely across natural and engineered systems, but little is known about the influence of DOM composition on its reactivity with manganese oxides. Here, we investigate bulk and molecular transformations of 30 diverse DOM samples after reaction with acid birnessite (MnO2), a strong oxidant that may react with DOM in Mn-rich environments or engineered treatment systems. The reaction of DOM with acid birnessite reduces Mn and forms DOM that is generally more aliphatic and lower in apparent molecular weight. However, the extent of reaction depends on the water type (e.g., wastewater, rivers) and highly aromatic DOM undergoes greater changes. Despite the variability in reactivity due to the DOM composition, aqueous products attributable to the oxidation of phenolic precursors are identified in waters analyzed by high-resolution mass spectrometry. The number of matched product formulas correlates significantly with indicators of DOM aromaticity, such as double-bond equivalents (p = 2.43 × 10-4). At the molecular level, highly aromatic, lignin-like carbon reacts selectively with acid birnessite in all samples despite the variability in initial DOM composition, resulting in the formation of a wide range of aqueous products. These findings demonstrate that DOM oxidation occurs in diverse waters but also suggest that reactivity with acid birnessite and the composition of the resulting aqueous DOM pool are composition-dependent and linked to the DOM source and initial aromaticity.

Simultaneous Kinetics of Selenite Oxidation and Sorption on δ-MnO2 in Stirred-Flow Reactors.

Selenium (Se) is an essential and crucial micronutrient for humans and animals, but excessive Se brings negativity and toxicity. The adsorption and oxidation of Se(IV) on Mn-oxide surfaces are important processes for understanding the geochemical fate of Se and developing engineered remediation strategies. In this study, the characterization of simultaneous adsorption, oxidation, and desorption of Se(IV) on δ-MnO2 mineral was carried out using stirred-flow reactors. About 9.5% to 25.3% of Se(IV) was oxidized to Se(VI) in the stirred-flow system in a continuous and slow process, with the kinetic rate constant k of 0.032 h-1, which was significantly higher than the apparent rate constant of 0.0014 h-1 obtained by the quasi-level kinetic fit of the batch method. The oxidation reaction was driven by proton concentration, and its rate also depended on the Se(IV) influent concentration, flow rate, and δ-MnO2 dosage. During the reaction of Se(IV) and δ-MnO2, Mn(II) was produced and adsorbed strongly on Mn oxide surfaces, which was evidenced by the total reflectance Fourier transform infrared (ATR-FTIR) results. The X-ray photoelectron spectroscopy (XPS) data indicated that the reaction of Se(VI) on δ-MnO2 produced Mn(III) as the main product. These results contribute to a deeper understanding of the interface chemical process of Se(IV) with δ-MnO2 in the environment.

Neutralization of high pH and alkalinity effluent from recycled concrete aggregate by common subgrade soil.

Use of recycled concrete aggregate (RCA) as highway basecourse material conserves virgin aggregate, reduces energy consumption and CO2 emissions, and may also decrease costs during construction. However, concerns remain over possible negative environmental impacts associated with high pH (>11) effluent from RCA in contact with water. This study examines the reactive transport of high-pH and high-alkalinity water, modeled on RCA leachate, through model subgrade soils. By developing an understanding of the reactions controlling effluent neutralization, this study aims to quantify the change in pH from the discharge site through surrounding subgrade soils. Four types of subgrade soils with a range of mineral composition, Atterberg limits, and cation exchange capacities (CECs) are examined. They include a clayey sand (SC10), low-plasticity clays (M14, SC25), and a high-plasticity clay (CH38). Batch reaction experiments are used to develop kinetic parameters describing the neutralization of high-pH and -alkalinity leachate by clay minerals through mineral dissolution and reprecipitation. Given this information, a reactive transport model incorporating advection, diffusion, and reaction is used to model the change in pH as a function of distance traveled through model subgrade soils and is applied to laboratory-scale column experiments. The rate at which the high pH front travels is directly related to a soil's clay mineral content. Soils with high CECs effectively delay the propagation of hydroxide front by the dissolution of clay minerals. This study demonstrates that common subgrade soils with moderate clay content will effectively neutralize high pH leachate initially produced by RCA.

Identifying the mechanisms of cation inhibition of phenol oxidation by acid birnessite.

Many phenolic compounds found as contaminants in natural waters are susceptible to oxidation by manganese oxides. However, there is often variability between oxidation rates reported in pristine matrices and studies using more environmentally relevant conditions. For example, the presence of cations generally results in slower phenolic oxidation rates. However, the underlying mechanism of cation interference is not well understood. In this study, cation co-solutes inhibit the transformation of four target phenols (bisphenol A, estrone, p-cresol, and triclosan) by acid birnessite. Oxidation rates for these compounds by acid birnessite follow the same trend (Na+ > K+ > Mg2+ > Ca2+) when cations are present as co-solutes. We further demonstrate that the same trend applies to these cations when they are absent from solution but pre-exchanged with the mineral. We analyze valence state, surface area, crystallinity, and zeta potential to characterize changes in oxide structure. The findings of this study show that pre-exchanged cations have a large effect on birnessite reactivity even in the absence of cation co-solutes, indicating that the inhibition of phenolic compound oxidation is not due to competition for surface sites, as previously suggested. Instead, the reaction inhibition is attributed to changes in aggregation and the mineral microstructure.

Effects of Co(II) ion exchange, Ni(II)- and V(V)-doping on the transformation behaviors of Cr(III) on hexagonal turbostratic birnessite-water interfaces.

Natural birnessite-like minerals are commonly enriched in various transitional metals (TMs), which greatly modify the mineral structure and properties. However few studies are yet conducted systematically on the effects of TM doping on birnessite reactivity towards Cr(III) oxidation. In the present study, the transformation behaviors of Cr(III) on Co-, Ni-, V-containing birnessites were investigated. Co and Ni doping generally decrease the mineral crystalline sizes and hydrodynamic sizes (DH) while V-doping greatly decreases the crystalline sizes but not the DH, owing to particle aggregation. Co and Ni firstly decrease and then increase the mineral zeta potentials (ζ) at pH4 while V decreases ζ. Electrochemical specific capacitances for Co-containing birnessites are gradually reduced, while those for Ni-doped birnessites are slightly reduced and for V-doped birnessites increased, which have a positively linear relationship with the amounts of Cr(III) oxidized by these samples. Cr(III) removal efficiencies from solution by these Co-, Ni- and V-containing birnessites are 26-51%, ∼62-72% and ∼96-100%, respectively, compared to ∼92% by pure birnessite. Cr(III) oxidation kinetics analysis demonstrates the gradual decrease of Mn(IV) and concurrent increase of Mn(III) and the adsorption of mainly Cr(III) on mineral surfaces. A negatively linear relationship exists between birnessite lateral sizes and the proportions of Mn(IV/III) consumed to oxidize Cr(III). Apparent initial Cr(III) oxidation rate (kobs) for Co-containing birnessites are greatly reduced, while those for Ni-doped samples moderately decreased and for V-doped samples first increased and then decreased. A positively or negatively linear relationship exists between kobs or the amount of Mn(II) released and the mineral Mn(IV) content respectively. Cr(III) oxidation probably initiates from layer edge sites of Ni-doped birnessites but the vacancies of Co- and V-containing birnessites. These results provide insights into the reaction mechanisms of Cr(III) with natural birnessite-like minerals.

Recycled concrete aggregate in base course applications: Review of field and laboratory investigations of leachate pH.

The prevalence of construction and demolition (C&D) waste and the concurrent demand for construction aggregate presents the opportunity to recycle C&D waste materials as substitutes for virgin aggregate. Commonly, recycled concrete aggregate (RCA) is used as base course in pavement construction. Environmentally responsible applications of RCA must consider the high pH leachate and trace element leaching risks reported in the literature. This review presents the methodology, results, and limitations of existing laboratory and field investigations of RCA leachate chemistry. Long-term highway field studies of RCA leachate illustrate that an initially high leachate pH approaches neutral within approximately one to two years of construction. Conversely, laboratory investigations of RCA leachate pH using batch reactor leaching tests and column leaching tests measure consistently high leachate pH (pH > 10). The discrepancies between field and laboratory measurements of RCA leachate pH suggest that the current laboratory methodology inadequately describes leachate conditions in the field. The authors recommend that future laboratory investigations consider intermittent wetting and drying cycles, eliminate particle abrasion, employ relevant contact times, and consider additional environmental processes that reduce leachate pH such as soil acidity and carbonation.

Impact of bisphenol A influent concentration and reaction time on MnO2 transformation in a stirred flow reactor.

Bisphenol A (BPA) is an endocrine disrupting compound commonly found in natural waters at concentrations that are considered harmful for aquatic life. Manganese(iii/iv) oxides are strong oxidants capable of oxidizing organic and inorganic contaminants, including BPA. Here we use δ-MnO2 in stirred flow reactors to determine if higher influent BPA concentrations, or introduction rates, lead to increased polymer production. A major BPA oxidation product, 4-hydroxycumyl alcohol (HCA), is formed through radical coupling, and was therefore used as a metric for polymer production in this study. The influent BPA concentration in stirred flow reactors did not affect HCA yield, suggesting that polymeric production is not strongly dependent on influent concentrations. However, changes in influent BPA concentration affected BPA oxidation rates and the rate of δ-MnO2 reduction. Lower aqueous Mn(ii) production was observed in reactors at higher BPA introduction rates, suggesting that single-electron transfer and polymer production are favored under these conditions. However, an examination of Mn(ii) sorption during these reactions indicated that the length of the reaction, rather than BPA introduction rate, caused enhanced aqueous Mn(ii) production in reactors with low introduction rates and longer reaction times due to increased opportunity for disproportionation and comproportionation. This study demonstrates the importance of investigating both the organic and inorganic reactants in the aqueous and solid phases in this complex reaction.

Stability of Ferrihydrite-Humic Acid Coprecipitates under Iron-Reducing Conditions.

Recent studies have suggested the potential for release of iron (hydr)oxide-bound organic carbon (OC) during dissimilatory iron oxide reduction (DIR). However, the stability of iron (hydr)oxide-bound OC in the presence of a natural microbial consortium capable of driving both OC metabolism and DIR has not been resolved. Pure ferrihydrite (Fhy) and Fhy-humic acid coprecipitates (Fhy-HA) were inoculated with a small quantity of freshwater sediment and incubated under anoxic conditions in the presence and absence of H2 or glucose as electron donors for DIR. H2 promoted DIR led to release of ca. 1 mM dissolved organic carbon (DOC). However, comparable amounts of DOC were released from both pure Fhy and Fhy-HA, similar to DOC levels in mineral-free, inoculum-only controls. These results suggest that the observed DOC release during H2-promoted DIR originated from OC contained in the inoculum as opposed to the much larger pool (ca. 38 mM) of OC in the Fhy-HA. Thus, DIR preferentially released sorbed OC with low aromaticity (inoculum OC) versus highly aromatic OC (HA) coprecipitated with iron oxide. Our findings provide new insight into the extent and mechanisms by which DIR is likely to influence aqueous/solid-phase OC partitioning in anoxic soils and sediments.

Use of Routine Soil Tests to Estimate Pb Bioaccessibility.

Soil lead (Pb) hazard level is contingent on bioavailability, but existing assays that estimate Pb bioavailability for human health risks are too expensive or otherwise inaccessible to many people that are impacted by Pb-contaminated soil. This study investigated the use of routine soil nutrient tests to estimate soil-Pb bioaccessibility as a surrogate measure of Pb bioavailability. A silt loam soil was spiked to a target concentration of 2000 mg Pb kg-1 with Pb(NO3)2 and amended with H3PO4 (varying P-to-Pb molar ratios) and KCl (Cl-to-P molar ratio of 2:5) to generate soils with similar total Pb concentrations but a range of Pb bioavailability (and bioaccessibility). Soils were extracted using Mehlich 3, Mehlich 1, Bray P1, Olsen, and  micronutrient (DTPA) methods, and the results were compared to U.S. Environmental Protection Agency method 1340 data as well as to extended X-ray absorption fine structure (EXAFS) spectroscopy. The Mehlich 3 and method 1340 treatment effect ratios were well-correlated ( r2 = 0.88, p ≤ 0.05), whereas Bray P1, DTPA, and Olsen results were more reflective of EXAFS data. Preliminary animal-feeding trials suggest that the Mehlich 3 is as effective as method 1340 at predicting the impact of P treatment on Pb relative bioavailability; however, both methods over-estimated the Pb hazard to mice in P-amended soil. Other routine soil tests that have heightened sensitivity to P amendment (e.g., Bray P1) may be promising candidates for Pb bioaccessibility assessment.

Dual Role of Humic Substances As Electron Donor and Shuttle for Dissimilatory Iron Reduction.

Dissimilatory iron-reducing bacteria (DIRB) are known to use humic substances (HS) as electron shuttles for dissimilatory iron reduction (DIR) by transferring electrons to HS-quinone moieties, which in turn rapidly reduce Fe(III) oxides. However, the potential for HS to serve as a source of organic carbon (OC) that can donate electrons for DIR is unknown. We studied whether humic acids (HA) and humins (HM) recovered from peat soil by sodium pyrophosphate extraction could serve as both electron shuttles and electron donors for DIR by freshwater sediment microorganisms. Both HA and HM served as electron shuttles in cultures amended with glucose. However, only HA served as an electron donor for DIR. Metagenomes from HA-containing cultures had an overrepresentation of genes involved in polysaccharide and to a lesser extent aromatic compound degradation, suggesting complex OC metabolism. Genomic searches for the porin-cytochrome complex involved in DIR resulted in matches to Ignavibacterium/Melioribacter, DIRB capable of polymeric OC metabolism. These results indicate that such taxa may have played a role in both DIR and decomposition of complex OC. Our results suggest that decomposition of HS coupled to DIR and other anaerobic pathways could play an important role in soil and sediment OC metabolism.