Artesian conditions in the Chilterns Chalk aquifer (North West of the London Basin) and the implications for surface water - groundwater interactions

The Chalk is a principal aquifer which provides an important resource in Southeast England. For two centuries, it allowed the establishment of a thriving watercress-growing industry, indirectly through diverted stream flow and directly, through the drilling of flowing artesian boreholes. The distribution of artesian boreholes across different catchments, suggests a regional control on vertical groundwater flow within the New Pit and Lewes Chalk units. Interrogation of location-specific information points to the confining role of a few key marls within the New Pit Chalk Formation, which can be traced up-catchment to where they naturally outcrop or have been exposed by quarrying. Evidence is found in geophysical logging of a number of boreholes across catchments, confirming a consistent pattern of the spatial distribution of such key markers. When tectonic stress was applied to the various Chalk Formations, the marl bands would have reacted producing more plastic deformation and less fractures in comparison with rigid rock strata. Such scenario would have created the conditions for secondary aquifer units, giving the Chalk confining or semi-confining hydraulic characteristics on a regional scale. This conceptual understanding helps explain the reasons that the river flow response to reductions in groundwater abstraction varies across the flow duration curve.

Model-Predicted Clinical Factors Impacting Patient-Specific Response of Sickle Cells to Voxelotor in a Microfluidic Platform

Background: Sickle cell disease (SCD) is a group of genetic disorders in which sickle hemoglobin polymerizes under deoxygenation, altering red blood cell (RBC) morphology and behavior. The properties of sickle RBCs contribute to increased viscosity of blood and occurrence of vaso-occlusions, a major aspect of SCD pathophysiology. Voxelotor is a novel FDA-approved treatment for SCD which modulates hemoglobin O 2 affinity, and while its known mechanism inhibits sickle polymerization, the impact on other aspects of SCD pathophysiology remain unknown. Thus, despite the new treatment option, highly variable clinical manifestation continues to be a hallmark of sickle cell and there is consequently a need to optimize the use of current therapies based on patient-specific factors. In this work, we leverage datasets generated from a unique microfluidic assay that measures blood flow behavior under varying oxygen tension in conjunction with novel statistical approaches to model and assess sources of variability in sickle blood flow response to voxelotor. Methods: RBCs from patients with SCD (n=28) were treated with voxelotor at 500 uM concentration. Treated samples and untreated controls were perfused through a microfluidic platform that dynamically modulates oxygen tension and measures flow velocity (Wood et al, 2012; Valdez et al, 2019). The area between curves (ABC) of the normalized velocity across the range of oxygen tension between treated and control conditions was calculated to quantify the effect of voxelotor for each sample (figure 1). A paired t-test was used to assess the difference in response between treated and untreated samples. Where available, clinical data including the hemoglobin fractions and complete blood count (CBC) were collected for each sample as predictor variables, and partial least squares regression (PLSR) modeling was used to assess the correlation of predictors and responses. Results: Voxelotor increased the velocity ABC from untreated to treated conditions (p<.0001). We observed that there were differences in response for velocity ABC between sickle cell genotypes (figure 2). Thus, generating separate PLSR models for distinct SCD genotypes revealed differences in sets of clinical factors that explained the most variance in response to voxelotor treatment. A 2-component model was constructed for the HbSC samples (n=6) that best explained variance in the data and had good predictive abilities (R 2X=.69, R 2Y=.97, Q 2=.74). Within this subset, clustering of variables related to hemolysis and inflammation were observed (figure 3). An equivalent model constructed for the HbSS samples (n=15) characterized the predictor variables but lacked predictive power of the response (R 2X=.74, R 2Y=.25, Q 2=.-0.21). Response to voxelotor for this model was most strongly correlated with HbA. Due to low sample size (n=2 samples with full set of predictors), predictive modeling was not performed for HbSβ 0 samples, however, these samples responded the least to voxelotor treatment. Conclusions: Our analysis quantified patient-specific differences in the blood flow response to voxelotor, showing a wide variability in response despite treatment by the same drug concentration. Genotype-specific multivariable models that take into account easily measurable clinical variables such as the CBC have the potential to explain the variability in patient response to voxelotor treatment. In HbSC samples, the WBC, platelet, and reticulocyte counts were highly correlated and strong predictors of response to voxelotor, which may point to markers of hemolysis and inflammation being useful in determining patients that can be optimally treated with this drug. In HbSS, response to voxelotor was mainly inversely correlated with HbA levels, which is a surrogate marker for blood transfusions, indicating that the effect of voxelotor is lessened for patients who are receiving transfusions. However, the low R2Y of this model highlights the clinical variability in this SCD genotype and consequent need for additional biomarkers of disease severity. In conclusion, our hybrid experimental-computational approach is able to identify clinical factors that highly impact the response of patient blood samples to treatment with voxelotor for HbSC patients, and highlights the need for precision therapy recommendations in SCD. Figure 1 Figure 1. Disclosures Lam: Sanguina, Inc.: Current holder of individual stocks in a privately-held company. Kemp: Parthenon Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Streamlined Multidisciplinary Work Flow Assesses Pipeline Slugging

This article, written by JPT Technology Editor Chris Carpenter, contains highlights of paper OTC 30172, “A Streamlined Multidisciplinary Work Flow for Pipeline-Slugging Assessment,” by Jeff Zhang, Saurav Jha, and Tim Matuszyk, Wood, prepared for the 2020 Offshore Technology Conference Asia, originally scheduled to be held in Kuala Lumpur, 2–6 November. The paper has not been peer reviewed. Copyright 2020 Offshore Technology Conference. Reproduced by permission. Free spans exist in subsea multiphase pipelines laid over undulating seabed profiles or across continental scarps for offshore field developments. Slug-flow-induced fatigue damage on the free spans can have a significant effect on project economics. Slug-flow assessments can prove time-consuming. The complete paper describes an integrated iterative approach between the flow-assurance and pipeline-engineering disciplines to streamline the work flow based on the value or cost associated with changes in input parameters that affect pipeline fatigue-assessment outcomes. Slug-Flow Assessment Work Flow The complete paper further details key goals for each step. Step 1: Plan Project Slug-Flow Design Requirements. Key to this step is to create a close interface between flow-assurance and pipeline engineers to discuss and align overall timing, critical decisions, and hold points that are required as part of the slug-flow assessment and any specific project-design considerations. Step 2: Execute Slug-Flow-Prediction Assessment. Slug-flow prediction typically is conducted by engineers using industry-standard multiphase dynamic-flow simulators. The step requires significant time and effort because of long simulation times and large data post-processing requirements. Step 3: Generate Slug-Flow Interface Data. The two methods typically used for converting flow-assurance slug-flow results into formats that can be used readily by pipeline engineers are the time-history approach and the time-dependent-matrix approach. Step 4: Execute Slug-Flow Response Assessment. This assessment typically is conducted by pipeline engineers to assess the effects of predicted slug-flow interface data on proposed pipeline con-figuration designs. Industry-standard finite-element-analysis (FEA) tools are used for this step. Step 5: Finalize Design Through Iteration and Optimization. Where the slug-flow response assessment results show excessive fatigue damage that affects feasibility of the proposed design, iteration and optimization are performed. Step 6: Consider Operational Monitoring Requirements. Operational fatigue monitoring can be considered if operational restrictions are required or if some level of risk or concern remains with the final design.

Collective flow in single-hit QCD kinetic theory

Motivated by recent interest in collectivity in small systems, we calculate the harmonic flow response to initial geometry deformations within weakly coupled QCD kinetic theory using the first correction to the free-streaming background. We derive a parametric scaling formula that relates harmonic flow in systems of different sizes and different generic initial gluon distributions. We comment on similarities and differences between the full QCD effective kinetic theory and the toy models used previously. Finally we calculate the centrality dependence of the integrated elliptic flow v2 in oxygen-oxygen, proton-lead and proton-proton collision systems.

Exhaustive Regressor Search (XRS) for Creating Models of Hydraulic Pumps and Motors

Physical models of fluid power systems rely on the validity of the principles used for creating such models. In many cases, pump and motor performance is considered a large contributor to the efficiency of a whole fluid power system and, is used to approximate the behavior of the component and the system coupled to it. Often, estimates of the power losses and efficiency of pumps and motors is limited to manufacturer test data or simplified assumptions based on first principles. However, the use of the limited test data or idealized assumptions reduces the accuracy of the models and limits the validity of the theoretical results. Moreover, the creation of accurate physical models, their numerical implementation using a computer to solve the model and the experimental validation is time consuming and costly. New advances in machine learning, statistical analysis and numerical methods can be used to reduce the time used to develop a model of a pump or motor producing similar or better results. This paper proposes the use of an autonomous and iterative algorithm to obtain linear regression coefficients necessary to characterize the flow response of a pump or motor from existing experimental data. In this study a multivariate linear model for predicting the flow output of a pump or a motor is derived from experimental data by iteratively adding data points and by iteratively and autonomously testing regressor combinations to find the best possible flow model.

How Turbulence Models Perform in Simulating Pipeflow Response to Targeted Wall-Shapes?

This study evaluates how Reynolds-Averaged-Navier-Stokes (RANS) models perform in simulating the characteristics of mean three-dimensional perturbed flows in pipes with targeted wall-shapes. Capturing such flow features using turbulence models is still challenging at high Reynolds numbers. The principal objective of this investigation is to evaluate which of the well-established RANS models can best predict the flow response and recovery characteristics in perturbed pipes at moderate and high Reynolds numbers (10000-158000). First, the flow profiles at various axial locations are compared between simulations and experiments. This is followed by assessing the well-known mean pipeflow scaling relations. The good agreement between our computationally predicted data using Standard k-epsilon model and those of experiments indicated that this model can accurately capture the pipeflow characteristics in response to introduced perturbation with smooth sinusoidal axial variations.

Caffeine alters thermoregulatory responses to exercise in the heat only in caffeine-habituated individuals: a double-blind placebo-controlled trial

We provide empirical evidence that acute caffeine ingestion exerts a thermoregulatory effect during exercise in the heat in caffeine-habituated individuals but not in nonhabituated individuals. Specifically, caffeine habituation was associated with a greater rise in esophageal temperature with caffeine compared with placebo, which appears to be driven by a blunted skin blood flow response. In contrast, no thermoregulatory differences were observed with caffeine in nonhabituated individuals. Caffeine did not affect sweating responses during exercise in the heat.