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Given expanding studies in epidemiology and disease-oriented human studies offering hundreds of associations between the human "ome" and disease, prioritizing molecules relevant to disease mechanisms among this growing breadth is important. Here, we link the circulating proteome to human heart failure (HF) propensity (via echocardiographic phenotyping and clinical outcomes) across the lifespan, demonstrating key pathways of fibrosis, inflammation, metabolism, and hypertrophy. We observe a broad array of genes encoding proteins linked to HF phenotypes and outcomes in clinical populations dynamically expressed at a transcriptional level in human myocardium during HF and cardiac recovery (several in a cell-specific fashion). Many identified targets do not have wide precedent in large-scale genomic discovery or human studies, highlighting the complementary roles for proteomic and tissue transcriptomic discovery to focus epidemiological targets to those relevant in human myocardium for further interrogation., Competing Interests: Declaration of interests S.G.D. is a consultant for Abbott, and S.G.D. and K.J.L. have industry research support from Novartis. R.V.S. has served as a consultant for Amgen, Cytokinetics, and Thryv Therapeutics (with options ownership in Thryv). R.V.S. is a co-inventor on a patent for ex-RNA signatures of cardiac remodeling and a pending patent on proteomic signatures of fitness and lung and liver diseases. R.V.S. also has stock options with Thryv Therapeutics. A.S.P. is a co-inventor on a pending patent for proteomic signatures of fitness, lung, and liver diseases. K.A. does ad hoc consulting for Tegus and Guidepoint and serves on a DSMB for Fortrea. M.N. has received speaking honoraria from Cytokinetics. K.J.L. serves as a consultant for Medtronic, Implicit Biosciences, Kiniksa Pharmaceuticals, and Cytokinetics. K.J.L. receives grant support from Amgen, Novartis, Kiniksa Pharmaceuticals, and Implicit Biosciences. S.D. is a co-founder and has equity in Thryv therapeutics and Switch Therapeutics. S.D. has received grant support from Abbot Laboratories and Bristol Myers Squib. S.D. is a co-inventor on a patent on tissue-specific EV-RNAs. R.K. has received personal fees from GSK, Astrazeneca, Boehringer Ingelheim, and CVS Caremark. S.J.S. has received consulting fees from 35Pharma, Abbott, Alleviant, AstraZeneca, Amgen, Aria CV, Axon Therapies, BaroPace, Bayer, Boehringer-Ingelheim, Boston Scientific, BridgeBio, Bristol Myers Squibb, Corvia, Cyclerion, Cytokinetics, Edwards Lifesciences, Eidos, eMyosound, Imara, Impulse Dynamics, Intellia, Ionis, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Prothena, ReCor, Regeneron, Rivus, SalubriusBio, Sardocor, Shifamed, Tectonic, Tenax, Tenaya, Ulink, and Ultromics. J.M.A. was employed by Amgen. J.W. reports consulting/scientific advisory board for Abiomed, Abbott, Astra Zeneca, Boehringer Ingelheim, and Cytokinetics within the last 24 months., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Climate influences near-surface biogeochemical processes and thereby determines the partitioning of carbon dioxide (CO 2 ) in shale, and yet the controls on carbon (C) weathering fluxes remain poorly constrained. Using a dataset that characterizes biogeochemical responses to climate forcing in shale regolith, we implement a numerical model that describes the effects of water infiltration events, gas exchange, and temperature fluctuations on soil respiration and mineral weathering at a seasonal timescale. Our modeling approach allows us to quantitatively disentangle the controls of transient climate forcing and biogeochemical mechanisms on C partitioning. We find that ~3% of soil CO 2 (1.02 mol C/m 2 /y) is exported to the subsurface during large infiltration events. Here, net atmospheric CO 2 drawdown primarily occurs during spring snowmelt, governs the aqueous C exports (61%), and exceeds the CO 2 flux generated by pyrite and petrogenic organic matter oxidation (~0.2 mol C/m 2 /y). We show that shale CO 2 consumption results from the temporal coupling between soil microbial respiration and carbonate weathering. This coupling is driven by the impacts of hydrologic fluctuations on fresh organic matter availability and CO 2 transport to the weathering front. Diffusion-limited transport of gases under transient hydrological conditions exerts an important control on CO 2(g) egress patterns and thus must be considered when inferring soil CO 2 drawdown from the gas phase composition. Our findings emphasize the importance of seasonal climate forcing in shaping the net contribution of shale weathering to terrestrial C fluxes and suggest that warmer conditions could reduce the potential for shale weathering to act as a CO 2 sink., Competing Interests: Competing interests statement:The authors declare no competing interest.

The dissolution of sulfide minerals can lead to hazardous arsenic levels in groundwater. This study investigates the oxidative dissolution of natural As-bearing sulfide minerals and the related release of arsenic under flow-through conditions. Column experiments were performed using reactive As-bearing sulfide minerals (arsenopyrite and löllingite) embedded in a sandy matrix and injecting oxic solutions into the initially anoxic porous media to trigger the mineral dissolution. Noninvasive oxygen measurements, analyses of ionic species at the outlet, and scanning electron microscopy allowed tracking the propagation of the oxidative dissolution fronts, the mineral dissolution progress, and the change in mineral surface composition. Process-based reactive transport simulations were performed to quantitatively interpret the geochemical processes. The experimental and modeling outcomes show that pore-water acidity exerts a key control on the dissolution of sulfide minerals and arsenic release since it determines the precipitation of secondary mineral phases causing the sequestration of arsenic and the passivation of the reactive mineral surfaces. The impact of surface passivation strongly depends on the flow velocity and on the spatial distribution of the reactive minerals. These results highlight the fundamental interplay of reactive mineral distribution and hydrochemical and hydrodynamic conditions on the mobilization of arsenic from sulfide minerals in flow-through systems.

Although mixing and surface complexation reactions are key processes for solute transport in porous media, their coupling has not been extensively investigated. In this work, we study the impact of mass-transfer limitations on heterogeneous reactions taking place at the solid-solution interface of a natural sandy porous medium under advection-dominated flow-through conditions. A comprehensive set of 36 column experiments with different grain sizes (0.64, 1.3 and 2.3 mm), seepage velocities (1, 30 and 90 m/day), and hydrochemical conditions were performed. The injection of NaBr solutions of different concentrations (1-100 mM) led to the release of protons via deprotonation reactions of the quartz surface. pH and solute concentration breakthrough curves were measured at the outlet of the columns and the propagation of pH fronts in the column setups was tracked inside the porous medium with non-invasive optode sensors. The experimental results show that the deprotonation of the reactive surfaces, resulting from their interactions with the injected ionic species, strongly depends on the hydrodynamic conditions and differs among the tested porous media despite their apparent similar surface properties. Reactive transport modeling was used to quantitatively interpret the experimental results and to analyze the effects of mass-transfer limited physical processes on surface complexation reactions, propagation of pH fronts, transport of major ions and spatio-temporal evolution of surface composition. A dual domain mass transfer formulation (DDMT) combined with a surface complexation model (SCM) allowed capturing the effects of incomplete mixing on the surface reactions and to reproduce the experimental observations collected in the experiments with high flow velocities. The SCM was parameterized with a single set of surface complexation parameters, accounting for the similar surface properties of the porous media, and was capable of describing the surface complexation mechanisms and their impact on the hydrochemistry over the large range of tested ionic strengths., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The oxidative dissolution of sulfide minerals, naturally present in the subsurface, is one of the major pathways of arsenic mobilization. This study investigates the release and fate of arsenic from arsenopyrite and löllingite oxidation under dynamic redox conditions. We performed multidimensional flow-through experiments focusing on the impact of chemical heterogeneity on arsenic mobilization and reactive transport. In the experimental setups the As-bearing sulfide minerals were embedded, with different concentrations and spatial distributions, into a sandy matrix under anoxic conditions. Oxic water flushed in the flow-through setups triggered the oxidative dissolution of the reactive minerals, the release of arsenic, as well as changes in pore water chemistry, surface-solution interactions and mineral precipitation. We developed a reactive transport model to quantitatively interpret the experimental results. The simulation outcomes showed that 40% of the arsenic released was reincorporated into a freshly precipitated iron-arsenate phase that created a coating on the mineral surface limiting the dissolution reactions. The faster dissolution rate of löllingite compared to arsenopyrite was responsible for sustaining the continuous release of As-contaminated plumes. The model also allowed shedding light on the spatial distribution, on the temporal dynamics, and on the interactions between arsenic sources (As-bearing minerals) and sinks (freshly formed secondary phases) in flow-through systems., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Arsenic (As) release and mobility in groundwater is coupled to the iron (Fe) cycling and the associated transformation of Fe-oxides present in sediments. Recent in situ experiments have provided observations on arsenic mobilization and co-occurring reductive mineral transformation when placing As-loaded ferrihydrite-coated sand for 80 days in wells of an As-contaminated aquifer of Northern China. However, the complex temporal change in solid-associated arsenic and the multiple geochemical processes occurring when the flowing groundwater contacts the As-loaded ferrihydrite-coated sand hamper a detailed evaluation of the experimental data set. In this study, we develop a modeling approach that allows a quantitative interpretation of arsenic release and ferrihydrite transformation observed during the in situ experiments. The model accounts for the interplay of abiotic and biotic geochemical processes (i.e., surface complexation, reductive dissolution, formation of secondary iron minerals, and arsenic sequestration into the newly formed minerals) involved in the transformation of Fe-oxides and controlling arsenic mobility. The results show the capability of the proposed approach to reproduce the temporal trends of solid arsenic and ferrihydrite concentrations, as well as the spatial variability of mineral transformation, observed in different wells using a common set of surface complexation parameters and kinetic rate constants. The simulation outcomes allowed us to disentangle the specific contribution of the different mechanisms controlling the release of arsenic. It was possible to identify an initial rapid but minor release of As (13-23% of the initial surface concentration) due to desorption from ferrihydrite, as well as the reduction of adsorbed As(V) to As(III) upon contact with the flowing anoxic groundwater. Successively, reductive dissolution of ferrihydrite caused the decrease of the amount of the Fe mineral phase and led to a major depletion of solid-associated arsenic. The produced Fe(II) catalyzed the ferrihydrite conversion into more crystalline Fe(III) oxides (i.e., lepidocrocite and goethite) through Ostwald ripening, and resulted in the formation of siderite and mackinawite upon reaction with carbonates and sulfides naturally present in the groundwater. The model results also showed that, whereas the decrease in surface sites during reductive dissolution of ferrihydrite promoted arsenic mobilization, the mineral transformation limited As release through its sequestration into the newly formed secondary mineral phases.

A dispersion-advection model was used to simulate the Elk river chemical spill 2014. The numerical and analytical solutions were used to predict the concentrations of 4-methylcyclohexane methanol (MCHM) at the water treatment plants located along the Elk and Kanawha rivers. The results are of similar magnitude as measured concentrations although a time-lag was found between modeled and measured plume arrival likely due to accumulation of systematic errors. Considering MCHM guidelines for drinking water, the spill represented a serious health threat through the water up taken by the treatment plant located on the Elk river and it also constituted a risk of contamination for the drinking water produced by treatment plants located on the Kanawha river.

Parents in 102 families with a 3- to 5-year-old child with developmental delays of uncertain etiology were interviewed concerning religion and adaptations to their child with delays. Religious parents were somewhat more familistic than were nonreligious parents, emphasized parental nurturance, and said that their child was an opportunity rather than a burden. Religious and nonreligious families were similar on other measures of developmental beliefs and social support. Religious parents described the "purpose" of their children with delays in their lives in emotionally powerful and meaningful ways that clearly helped them, although direct measures of peace of mind and emotional adjustment did not differ between religious and nonreligious families.