Exploring substitution random functions composed of stationary multi-Gaussian processes.

Simulation of random fields is widely used in Earth sciences for modeling and uncertainty quantification. The spatial features of these fields may have a strong impact on the forecasts made using these fields. For instance, in flow and transport problems the connectivity of the permeability fields is a crucial aspect. Multi-Gaussian random fields are the most common tools to analyze and model continuous fields. Their spatial correlation structure is described by a covariance or variogram model. However, these types of spatial models are unable to represent highly or poorly connected structures even if a broad range of covariance models can be employed. With this type of model, the regions with values close to the mean are always well connected whereas the regions of low or high values are isolated. Substitution random functions (SRFs) belong to another broad class of random functions that are more flexible. SRFs are constructed by composing (Z=Y∘T) two stochastic processes: the directing function T (latent field) and the coding process Y (modifying the latent field in a stochastic manner). In this paper, we study the properties of SRFs obtained by combining stationary multi-Gaussian random fields for both T and Y with bounded variograms. The resulting SRFs Z are stationary, but as T has a finite variance Z is not ergodic for the mean and the covariance. This means that single realizations behave differently from each other. We propose a simple technique to control which values (low, intermediate, or high) are connected. It consists of adding a control point on the process Y to guide every single realization. The conditioning to local values is obtained using a Gibbs sampler.

Towards Improved Remedial Outcomes in Categorical Aquifers with an Iterative Ensemble Smoother.

Categorical parameter distributions consisting of geologic facies with distinct properties, for example, high-permeability channels embedded in a low-permeability matrix, are common at contaminated sites. At these sites, low-permeability facies store solute mass, acting as secondary sources to higher-permeability facies, sustaining concentrations for decades while increasing risk and cleanup costs. Parameter estimation is difficult in such systems because the discontinuities in the parameter space hinder the inverse problem. This paper presents a novel approach based on Traveling Pilot Points (TRIPS) and an iterative ensemble smoother (IES) to solve the categorical inverse problem. Groundwater flow and solute transport in a hypothetical aquifer with a categorical parameter distribution are simulated using MODFLOW 6. Heads and concentrations are recorded at multiple monitoring locations. IES is used to generate posterior ensembles assuming a TRIPS prior and an approximate multi-Gaussian prior. The ensembles are used to predict solute concentrations and mass into the future. The evaluation also includes an assessment of how the number of measurements and the choice of the geological prior determine the characteristics of the posterior ensemble and the resulting predictions. The results indicate that IES was able to efficiently sample the posterior distribution and showed that even with an approximate geological prior, a high degree of parameterization and history matching could lead to parameter ensembles that can be useful for making certain types of predictions (heads, concentrations). However, the approximate geological prior was insufficient for predicting mass. The analysis demonstrates how decision-makers can quantify uncertainty and make informed decisions with an ensemble-based approach.

Automatic stochastic 3D clay fraction model from tTEM survey and borehole data.

In most urbanized and agricultural areas of central Europe, the shallow underground is constituted of Quaternary deposits which are often the most extensively used layers (water pumping, shallow geothermic, material excavation). All these deposits are often complexly intertwined, leading to high spatial variability and high complexity. Geophysical data can be a fast and reliable source of information about the underground. Still, the integration of these data can be time-consuming, it lacks realistic interpolation in a full 3D space, and the final uncertainty is often not represented. In this study, we propose a new methodology to combine boreholes and geophysical data with uncertainty in an automatic framework. A spatially varying translator function that predicts the clay fraction from resistivity is inverted using boreholes description as control points. It is combined with a 3D stochastic interpolation framework based on a Multiple Points Statistics algorithm and Gaussian Random Function. This novel workflow allows incorporating robustly the data and their uncertainty and requires less user intervention than the already existing workflows. The methodology is illustrated for ground-based towed transient electromagnetic data (tTEM) and borehole data from the upper Aare valley, Switzerland. In this location, a 3D realistic high spatial resolution model of clay fraction was obtained over the whole valley. The very dense data set allowed to demonstrate the quality of the predicted values and their corresponding uncertainties using cross-validation.

An Attempt to Boost Posterior Population Expansion Using Fast Machine Learning Algorithms.

In hydrogeology, inverse techniques have become indispensable to characterize subsurface parameters and their uncertainty. When modeling heterogeneous, geologically realistic discrete model spaces, such as categorical fields, Monte Carlo methods are needed to properly sample the solution space. Inversion algorithms use a forward operator, such as a numerical groundwater solver. The forward operator often represents the bottleneck for the high computational cost of the Monte Carlo sampling schemes. Even if efficient sampling methods (for example Posterior Population Expansion, PoPEx) have been developed, they need significant computing resources. It is therefore desirable to speed up such methods. As only a few models generated by the sampler have a significant likelihood, we propose to predict the significance of generated models by means of machine learning. Only models labeled as significant are passed to the forward solver, otherwise, they are rejected. This work compares the performance of AdaBoost, Random Forest, and convolutional neural network as classifiers integrated with the PoPEx framework. During initial iterations of the algorithm, the forward solver is always executed and subsurface models along with the likelihoods are stored. Then, the machine learning schemes are trained on the available data. We demonstrate the technique using a simulation of a tracer test in a fluvial aquifer. The geology is modeled by the multiple-point statistical approach, the field contains four geological facies, with associated permeability, porosity, and specific storage values. MODFLOW is used for groundwater flow and transport simulation. The solution of the inverse problem is used to estimate the 10 days protection zone around the pumping well. The estimated speed-ups with Random Forest and AdaBoost were higher than with the convolutional neural network. To validate the approach, computing times of inversion without and with machine learning schemes were computed and the error against the reference solution was calculated. For the same mean error, accelerated PoPEx achieved a speed-up rate of up to 2 with respect to the standard PoPEx.

Clinical relevance of genotype-phenotype correlations beyond vascular events in a cohort study of 1500 Marfan syndrome patients with FBN1 pathogenic variants.

PURPOSE: Marfan syndrome (MFS) is a connective tissue disorder in which several systems are affected with great phenotypic variability. Although known to be associated with pathogenic variants in the FBN1 gene, few genotype-phenotype correlations have been found in proband studies only. METHODS: In 1,575 consecutive MFS probands and relatives from the most comprehensive database worldwide, we established survival curves and sought genotype-phenotype correlations. RESULTS: A risk chart could be established with clinical and genetic data. Premature termination codon variants were not only associated with a shorter life expectancy and a high lifelong risk of aortic event, but also with the highest risk of severe scoliosis and a lower risk for ectopia lentis (EL) surgery. In-frame variants could be subdivided according to their impact on the cysteine content of fibrillin-1 with a global higher severity for cysteine loss variants and the highest frequency of EL surgery for cysteine addition variants. CONCLUSION: This study shows that FBN1 genotype-phenotype correlations exist for both aortic and extra-aortic features. It can be used for optimal risk stratification of patients with a great importance for genetic counseling and personalized medicine. This also provides additional data for the overall understanding of the role of fibrillin-1 in various organs.

Using Generative Adversarial Networks as a Fast Forward Operator for Hydrogeological Inverse Problems.

Subsurface characterization using inverse techniques constitutes one of the fundamental elements of hydrogeological modeling applications. Available methods to solve inverse problems rely on a forward operator that predicts state variables for a given set of subsurface parameters. As the number of model parameters to be estimated increases, forward operations incur a significant computational demand. In this paper, we investigate the use of conditional generative adversarial networks (cGAN) as an emulator for the forward operator in the context of a hydrogeological inverse problem. We particularly investigate if the cGAN can be used to replace the forward operator used in the adaptive importance sampling method posterior population expansion (PoPEx) with reasonable accuracy and feasible computation requirement. The cGAN model trained on channelized geological structures has shown that the cGAN is able to reproduce the state variables corresponding to a certain parameter field. Hence, its integration in PoPEx yielded satisfactory results. In terms of the computational demand, the use of cGAN as a surrogate forward model reduces the required computational time up to 80% for the problem defined in the study. However, the training time required to create a model seems to be the major drawback of the method.

A 2D hyperspectral library of mineral reflectance, from 900 to 2500 nm.

Mineral identification using machine learning requires a significant amount of training data. We built a library of 2D hyperspectral images of minerals. The library contains reflectance images of 130 samples, of 76 distinct minerals, with more than 3.9 million data points. In order to produce this dataset, various well-characterized mineral samples were scanned, using a SPECIM Short Wave Infrared (SWIR) camera, which captures wavelengths from 900 to 2500 nm. Minerals were selected to represent all the mineral classes and the most common mineral occurrences. For each sample, the following data are provided: (a) At least one hyperspectral image of the sample, consisting of 256 wavelengths between 900 and 2500 nm. The raw data, the high dynamic range (HDR) image, and the masked HDR image are provided for each scan (each of them in HDF5 format). (b) A text file describing the sample, providing supplementary information for the subsequent analysis (c) RGB images (JPEG files) and automated 3D reconstructions (Stanford Triangle PLY files). These data help the user to visualize and understand specific sample characteristics. 2D hyperspectral images were produced for each mineral, which consist of many different spectra with high diversity. The scans feature similar spectra than the ones in other available spectral libraries. An artificial neural network was trained to demonstrate the high quality of the dataset. This spectral library is mainly aimed at training machine learning algorithms, such as neural networks, but can be also used as validation data for other types of classification algorithms.

[Immunotherapy with immune checkpoint inhibitors and hepatitis]. / Immunothérapie par inhibiteurs de points de contrôle immunitaire et hépatite.

Immunotherapy, with « checkpoint ¼ inhibitors (CPIs), has become an essential therapeutic weapon against cancer. Autoimmune disorders related to overactivation of the immune system are well known side effects. The risk of reactivation of the hepatitis B and C viruses and exacerbation of the hepatitis, known from the introduction of immunosuppressive drugs such as chemotherapy, is poorly documented under immunotherapy. In this article, we discuss the issue of immunotherapy in patients presented with hepatitis using two approaches: the risks of immunotherapy in these situations and the management by disruption of liver tests under immunotherapy.

L'immunothérapie, avec les inhibiteurs de points de contrôle immunitaire « immune checkpoint inhibitors ¼, est devenue une arme thérapeutique essentielle contre de nombreux cancers. Les troubles autoimmuns liés à la suractivation du système immunitaire sont des effets secondaires bien connus. Le risque de réactivation des virus de l'hépatite B et C ou d'exacerbation de l'hépatite, connu lors de l'introduction de médicaments immunosuppresseurs telles les chimiothérapies, est peu documenté sous immunothérapie. Dans cet article, nous aborderons la question de l'immunothérapie chez des patients présentant une hépatite B ou C selon deux approches : les risques encourus à introduire une immunothérapie dans ces situations et la gestion d'une perturbation des tests hépatiques sous immunothérapie.

Generation of 3D Spatially Variable Anisotropy for Groundwater Flow Simulations.

Sedimentary units generally present anisotropy in their hydraulic properties, with higher hydraulic conductivity along bedding planes, rather than perpendicular to them. This common property leads to a modeling challenge if the sedimentary structure is folded. In this paper, we show that the gradient of the geological potential used by implicit geological modeling techniques can be used to compute full hydraulic conductivity tensors varying in space according to the geological orientation. For that purpose, the gradient of the potential, a vector normal to the bedding, is used to construct a rotation matrix that allows the estimation of the 3D hydraulic conductivity tensor in a single matrix operation. A synthetic 2D cross section example is used to illustrate the method and show that flow simulations performed in such a folded environment are highly influenced by this rotating anisotropy. When using the proposed method, the streamlines follow very closely the folded formation. This is not the case with an isotropic model.

Apolipoprotein H expression is associated with IL28B genotype and viral clearance in hepatitis C virus infection.

BACKGROUND & AIMS: HCV requires host lipid metabolism for replication, and apolipoproteins have been implicated in the response to treatment. METHODS: We examined plasma apolipoprotein concentrations in three cohorts of patients: mono-infected patients with symptomatic acute hepatitis C (aHCV); those undergoing treatment for chronic hepatitis C (cHCV); and HIV/HCV co-infected patients being treated for their chronic hepatitis C. We also evaluated associations between apolipoproteins and IL28B polymorphisms, a defined genetic determinant of viral clearance. RESULTS: Plasma apolipoprotein H (ApoH) levels were significantly higher in patients who achieved spontaneous clearance or responded to pegylated-interferon/ribavirin therapy. Strikingly, patients carrying the IL28B rs12979860 CC SNP correlated with the plasma concentration of ApoH in all three cohorts. Both ApoH and IL28B CC SNP were associated with HCV clearance in univariate analysis. Additional multivariate analysis revealed that the association between IL28B and HCV clearance was closely linked to that of Apo H and HCV clearance, suggesting that both belong to the same biological pathway to clearance. The association between IL28B CC SNP and ApoH was not observed in healthy individuals, suggesting that early post-infection events trigger differential ApoH expression in an IL28B allele dependent manner. CONCLUSIONS: This relationship identifies ApoH as the first induced protein quantitative trait associated with IL28B, and characterises a novel host factor implicated in HCV clearance.

Early-onset osteoarthritis, Charcot-Marie-Tooth like neuropathy, autoimmune features, multiple arterial aneurysms and dissections: an unrecognized and life threatening condition.

BACKGROUND: Severe osteoarthritis and thoracic aortic aneurysms have recently been associated with mutations in the SMAD3 gene, but the full clinical spectrum is incompletely defined. METHODS: All SMAD3 gene mutation carriers coming to our centre and their families were investigated prospectively with a structured panel including standardized clinical workup, blood tests, total body computed tomography, joint X-rays. Electroneuromyography was performed in selected cases. RESULTS: Thirty-four SMAD3 gene mutation carriers coming to our centre were identified and 16 relatives were considered affected because of aortic surgery or sudden death (total 50 subjects). Aortic disease was present in 72%, complicated with aortic dissection, surgery or sudden death in 56% at a mean age of 45 years. Aneurysm or tortuosity of the neck arteries was present in 78%, other arteries were affected in 44%, including dissection of coronary artery. Overall, 95% of mutation carriers displayed either aortic or extra-aortic arterial disease. Acrocyanosis was also present in the majority of patients. Osteoarticular manifestations were recorded in all patients. Joint involvement could be severe requiring surgery in young patients, of unusual localization such as tarsus or shoulder, or mimicking crystalline arthropathy with fibrocartilage calcifications. Sixty eight percent of patients displayed neurological symptoms, and 9 suffered peripheral neuropathy. Electroneuromyography revealed an axonal motor and sensory neuropathy in 3 different families, very evocative of type II Charcot-Marie-Tooth (CMT2) disease, although none had mutations in the known CMT2 genes. Autoimmune features including Sjogren's disease, rheumatoid arthritis, Hashimoto's disease, or isolated autoantibodies- were found in 36% of patients. INTERPRETATION: SMAD3 gene mutations are associated with aortic dilatation and osteoarthritis, but also autoimmunity and peripheral neuropathy which mimics type II Charcot-Marie-Tooth.

New methods to estimate 2D water level distributions of dynamic rivers.

River restoration measures are becoming increasingly popular and are leading to dynamic river bed morphologies that in turn result in complex water level distributions in a river. Disconnected river branches, nonlinear longitudinal water level profiles and morphologically induced lateral water level gradients can evolve rapidly. The modeling of such river-groundwater systems is of high practical relevance in order to assess the impact of restoration measures on the exchange flux between a river and groundwater or on the residence times between a river and a pumping well. However, the model input includes a proper definition of the river boundary condition, which requires a detailed spatial and temporal river water level distribution. In this study, we present two new methods to estimate river water level distributions that are based directly on measured data. Comparing generated time series of water levels with those obtained by a hydraulic model as a reference, the new methods proved to offer an accurate and faster alternative with a simpler implementation.

Modeling fine-scale geological heterogeneity--examples of sand lenses in tills.

Sand lenses at various spatial scales are recognized to add heterogeneity to glacial sediments. They have high hydraulic conductivities relative to the surrounding till matrix and may affect the advective transport of water and contaminants in clayey till settings. Sand lenses were investigated on till outcrops producing binary images of geological cross-sections capturing the size, shape and distribution of individual features. Sand lenses occur as elongated, anisotropic geobodies that vary in size and extent. Besides, sand lenses show strong non-stationary patterns on section images that hamper subsequent simulation. Transition probability (TP) and multiple-point statistics (MPS) were employed to simulate sand lens heterogeneity. We used one cross-section to parameterize the spatial correlation and a second, parallel section as a reference: it allowed testing the quality of the simulations as a function of the amount of conditioning data under realistic conditions. The performance of the simulations was evaluated on the faithful reproduction of the specific geological structure caused by sand lenses. Multiple-point statistics offer a better reproduction of sand lens geometry. However, two-dimensional training images acquired by outcrop mapping are of limited use to generate three-dimensional realizations with MPS. One can use a technique that consists in splitting the 3D domain into a set of slices in various directions that are sequentially simulated and reassembled into a 3D block. The identification of flow paths through a network of elongated sand lenses and the impact on the equivalent permeability in tills are essential to perform solute transport modeling in the low-permeability sediments.

Pentoxifylline does not decrease short-term mortality but does reduce complications in patients with advanced cirrhosis.

BACKGROUND & AIMS: Pentoxifylline, an inhibitor of tumor necrosis factor-alpha, is given to patients with liver diseases, but its effects in patients with advanced cirrhosis are unknown. We performed a randomized, placebo-controlled, double-blind trial of its effects in patients with cirrhosis. METHODS: A total of 335 patients with cirrhosis (Child-Pugh class C) were assigned to groups given either pentoxifylline (400 mg, orally, 3 times daily; n = 164) or placebo (n = 171) for 6 months. The primary end point was mortality at 2 months. Secondary end points were mortality at 6 months and development of liver-related complications. RESULTS: By 2 months, 28 patients in the pentoxifylline group (16.5%) and 31 in the placebo group (18.2%) had died (P = .84). At 6 months, 50 patients in the pentoxifylline group (30.0%) and 54 in the placebo group (31.5%) had died (P = .75). The proportions of patients without complications (eg, bacterial infection, renal insufficiency, hepatic encephalopathy, or gastrointestinal hemorrhage) were higher in the pentoxifylline group than in the placebo group at 2 months (78.6% vs 63.4%; P = .006) and 6 months (66.8% vs 49.7%; P = .002). The probability of survival without complications was higher in the pentoxifylline group than in the placebo group at 2 and 6 months (P = .04). In multivariate analysis, the factors associated with death were age, the Model for End-Stage Liver Disease score, and presence of early-stage carcinoma. Treatment with pentoxifylline was the only factor associated with liver-related complications. CONCLUSIONS: Although pentoxifylline does not decrease short-term mortality in patients with advanced cirrhosis, it does reduce the risk of complications.

Truncated plurigaussian simulations to characterize aquifer heterogeneity.

Integrating geological concepts, such as relative positions and proportions of the different lithofacies, is of highest importance in order to render realistic geological patterns. The truncated plurigaussian simulation method provides a way of using both local and conceptual geological information to infer the distributions of the facies and then those of hydraulic parameters. The method (Le Loc'h and Galli 1994) is based on the idea of truncating at least two underlying multi-Gaussian simulations in order to create maps of categorical variable. In this article, we show how this technique can be used to assess contaminant migration in highly heterogeneous media. We illustrate its application on the biggest contaminated site of Switzerland. It consists of a contaminant plume located in the lower fresh water Molasse on the western Swiss Plateau. The highly heterogeneous character of this formation calls for efficient stochastic methods in order to characterize transport processes.

Stochastic hydrogeology: what professionals really need?

Quantitative hydrogeology celebrated its 150th anniversary in 2006. Geostatistics is younger but has had a very large impact in hydrogeology. Today, geostatistics is used routinely to interpolate deterministically most of the parameters that are required to analyze a problem or make a quantitative analysis. In a small number of cases, geostatistics is combined with deterministic approaches to forecast uncertainty. At a more academic level, geostatistics is used extensively to study physical processes in heterogeneous aquifers. Yet, there is an important gap between the academic use and the routine applications of geostatistics. The reasons for this gap are diverse. These include aspects related to the hydrogeology consulting market, technical reasons such as the lack of widely available software, but also a number of misconceptions. A change in this situation requires acting at different levels. First, regulators must be convinced of the benefit of using geostatistics. Second, the economic potential of the approach must be emphasized to customers. Third, the relevance of the theories needs to be increased. Last, but not least, software, data sets, and computing infrastructure such as grid computing need to be widely available.

Management practices for gastrointestinal hemorrhage related to portal hypertension in cirrhotic patients: evaluation of the impact of the Paris consensus workshop.

OBJECTIVES: The purpose of this before-after observational survey was to evaluate compliance with good clinical practice guidelines for gastrointestinal hemorrhage related to portal hypertension and the impact of the French Consensus Workshop held in Paris in 2003. METHODS: Data were recorded concerning episodes of gastrointestinal hemorrhage occurring in cirrhotic patients using a survey questionnaire in 2003 before the workshop and again in 2004. RESULTS: Seventy-six index episodes were included in 2003 and 84 in 2004 in patients attending French hospitals. Before hospital admission, primary prophylaxis was similar in 2003 and 2004, but beta blockers were used alone more often in 2004 for secondary prophylaxis (42% vs 19%, P=0.018). The time from onset of bleeding to hospital admission was greater than 12 hours for 43 and 42% of patients and was not shorter in the event of recurrent hemorrhage. At admission, vasoactive drugs were given earlier in 2004 (<2h: 68% vs 35%, P<0.001). Use of antibiotic prophylaxis was similar in 2003 and 2004 (70% vs 61%, P=0.098), and was more common for Child-Pugh B or C patients (P=0.044). CONCLUSION: The Paris Consensus Workshop enabled improved clinical practices. Weak points were insufficient screening for cirrhosis, long delay before admission, insufficient use of antibiotic prophylaxis which should be systematic.

Management of digestive bleeding related to portal hypertension in cirrhotic patients: A French multicenter cross-sectional practice survey.

AIM: To investigate the conformity of management practices of gastrointestinal hemorrhage in cirrhotic patients with relevant guidelines. METHODS: A questionnaire on the management of digestive bleeding was completed for all consecutive cirrhotic patients admitted to 31 French hospitals. RESULTS: One hundred and twenty-six bleeding events were recorded. It was the first bleeding episode in 79 patients (63%), of whom 40 (51%) had a prior diagnosis of cirrhosis and 25 (32%) had previously undergone an endoscopy. The bleeding episode was a recurrence in 46 patients (37%). The median time between onset and admission was 4 h, but exceeded 12 h in 42% of cases. There was an agreement between centers for early vasoactive drug administration (87% of cases), association with ligation (42%) more often than sclerosis (21%) at initial endoscopy, and antibiotic prophylaxis (64%). By contrast, prescription of beta-blockade alone or in combination (0 to 100%, P = 0.003) for secondary prophylaxis and lactulose (26% to 86%, P = 0.04), differed among centers. CONCLUSION: In French hospitals, management of bleeding related to portal hypertension in cirrhotic patients is generally in keeping with the consensus. Broad variability still remains concerning beta-blockade use for secondary prophylaxis. Screening for esophageal varices, the use of antibiotic prophylaxis and patients information need to be improved.

Approximate discharge for constant head test with recharging boundary.

The calculation of the discharge to a constant drawdown well or tunnel in the presence of an infinite linear constant head boundary in an ideal confined aquifer usually relies on the numerical inversion of a Laplace transform solution. Such a solution is used to interpret constant head tests in wells or to roughly estimate ground water inflow into tunnels. In this paper, a simple approximate solution is proposed. Its maximum relative error is on the order of 2% as compared to the exact analytical solution. The approximation is a weighted mean between the early-time and late-time asymptotes.