Limits of applicability of the advection-dispersion model in aquifers containing connected high-conductivity channels

This is the published version. Copyright American Geophysical Union[1] The macrodispersion model from stochastic transport theory is demonstrated to be of limited utility when applied to heterogeneous aquifer systems containing narrow connected pathways. This is so even when contrasts in hydraulic conductivity (K) are small and variance in ln K is less than 0.10. We evaluated how well an advection-dispersion model (ADM) could be used to represent solute plumes transported through mildly heterogeneous three-dimensional (3-D) systems characterized by a well-connected dendritic network of 10 cm wide high-K channels. Each high-K channel network was generated using an invasion percolation algorithm and consisted of ∼10% by volume high-K regions. Contrasts in K between the channels and matrix were varied systematically from 2:1 to 30:1, corresponding to ln K values ranging from 0.04 to 1.05. Simulations involved numerical models with 3-D decimeter discretization, and each model contained 2–4 million active cells. Transport through each channel network considered only the processes of advection and molecular diffusion. In every case, the temporal change in the second spatial moment of concentrations was linear, with R2 values ranging from 0.97 to 0.99. The third spatial moment, or alternatively, the skewness coefficient values, indicated significant tailing downstream of the plume center. For each case, a corresponding ADM was used to simulate transport through the system. The corresponding ADM employed the effective mean hydraulic conductivity that reproduced the total discharge through the channel network system under an identical ambient gradient. Dispersivity values used in the ADM were obtained from the temporal change in the second spatial moments of concentrations for the plumes in the channel network systems and ranged from 0.014 m to 0.85 m. The results indicate that as the conductivity contrast between the channels and matrix increased, the simulated plumes in the channel network system became more and more asymmetric, with little solute dispersed upstream of the plume center and extensive downstream spreading of low concentrations. Distinctly different spreading was found upstream versus downstream of the plume center. The ADM failed to capture this asymmetry. Comparison of each plume in the channel network system with the corresponding plume produced using the corresponding ADM showed a maximum correlation of only 0.64 and a minimum fractional error of 0.29 for cases in which the log K variance was ∼0.20 (ln K variance was ∼1.0). At early times the correlations were as low as 0.40. The greatest correlation occurred at late times and for cases in which a wide source was considered

Physical Pictures of Transport in Heterogeneous Media: Advection-Dispersion, Random Walk and Fractional Derivative Formulations

The basic conceptual picture and theoretical basis for development of transport equations in porous media are examined. The general form of the governing equations is derived for conservative chemical transport in heterogeneous geological formations, for single realizations and for ensemble averages of the domain. The application of these transport equations is focused on accounting for the appearance of non-Fickian (anomalous) transport behavior. The general ensemble-averaged transport equation is shown to be equivalent to a continuous time random walk (CTRW) and reduces to the conventional forms of the advection-dispersion equation (ADE) under highly restrictive conditions. Fractional derivative formulations of the transport equations, both temporal and spatial, emerge as special cases of the CTRW. In particular, the use in this context of L{\'e}vy flights is critically examined. In order to determine chemical transport in field-scale situations, the CTRW approach is generalized to non-stationary systems. We outline a practical numerical scheme, similar to those used with extended geological models, to account for the often important effects of unresolved heterogeneities.Comment: 14 pages, REVTeX4, accepted to Wat. Res. Res; reference adde

Lactobacillus rhamnosus GG-supplemented formula expands butyrate-producing bacterial strains in food allergic infants.

Dietary intervention with extensively hydrolyzed casein formula supplemented with Lactobacillus rhamnosus GG (EHCF+LGG) accelerates tolerance acquisition in infants with cow's milk allergy (CMA). We examined whether this effect is attributable, at least in part, to an influence on the gut microbiota. Fecal samples from healthy controls (n=20) and from CMA infants (n=19) before and after treatment with EHCF with (n=12) and without (n=7) supplementation with LGG were compared by 16S rRNA-based operational taxonomic unit clustering and oligotyping. Differential feature selection and generalized linear model fitting revealed that the CMA infants have a diverse gut microbial community structure dominated by Lachnospiraceae (20.5±9.7%) and Ruminococcaceae (16.2±9.1%). Blautia, Roseburia and Coprococcus were significantly enriched following treatment with EHCF and LGG, but only one genus, Oscillospira, was significantly different between infants that became tolerant and those that remained allergic. However, most tolerant infants showed a significant increase in fecal butyrate levels, and those taxa that were significantly enriched in these samples, Blautia and Roseburia, exhibited specific strain-level demarcations between tolerant and allergic infants. Our data suggest that EHCF+LGG promotes tolerance in infants with CMA, in part, by influencing the strain-level bacterial community structure of the infant gut

A geostatistical framework for incorporating transport information in estimating the distribution of a groundwater contaminant plume

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95253/1/wrcr10904.pd

Recent advances in food allergy

Food allergy is a public health issue that has significantly increased worldwide in the past decade, affecting consumers’ quality of life and making increasing demands on health service resources. Despite recent advances in many areas of diagnosis and treatment, our general knowledge of the basic mechanisms of the disease remain limited i.e., not at pace with the exponential number of new cases and the explosion of new technologies. Many important key questions remain: What defines a major allergen? Why do some individuals develop food allergies and others do not? Which are the environmental factors? Could the environmental factors be monitored through epigenetics or modified by changes in the microbiome? Can tolerance to food be induced? Why are some foods more likely to trigger allergies than others? Does the route and timing of exposure have any role on sensitization? These and many other related questions remain unanswered. In this short review some of these topics are addressed in the light of recent advances in the area

Drugging the epigenome in the age of precision medicine

Abstract Background Modulating the epigenome has long been considered a potential opportunity for therapeutic intervention in numerous disease areas with several approved therapies marketed, primarily for cancer. Despite the overall promise of early approaches, however, these drugs have been plagued by poor pharmacokinetic and safety/tolerability profiles due in large part to off-target effects and a lack of specificity. Results Recently, there has been marked progress in the field on a new generation of epigenomic therapies which address these challenges directly by targeting defined loci with highly precise, durable, and tunable approaches. Here, we review the promise and pitfalls of epigenetic drug development to date and provide an outlook on recent advances and their promise for future therapeutic applications. Conclusions Novel therapeutic modalities leveraging epigenetics and epigenomics with increased precision are well positioned to advance the field and treat patients across disease areas in the coming years