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Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus. Many new studies have been reported recently that describe EoE management. An expert panel was convened by the American Gastroenterological Association Institute and the Joint Task Force on Allergy-Immunology Practice Parameters to provide a technical review to be used as the basis for an updated clinical guideline. This technical review was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Eighteen focused EoE management questions were considered, with 15 answered using the GRADE framework and 3 with a narrative summary. There is moderate certainty in the evidence that topical glucocorticosteroids effectively reduce esophageal eosinophil counts to

Simple Summary: Obesity is a clear risk factor for future colorectal cancer (CRC), but its impact on mortality remains to be fully elucidated. Prior studies have had methodologic limitations, and key variables remain under-investigated. In this study of prospectively collected data from the Multiethnic Cohort, pre-diagnosis BMI trajectories were not associated with CRC-specific or all-cause mortality. Factors associated with mortality included African American race or Hawaiian ethnicity, smoking, and diabetes. Accounting for long-term BMI trajectories before diagnosis and other relevant factors demonstrates that obesity is not protective of mortality after CRC diagnosis. Background: Prior studies are inconclusive regarding the effect of obesity on mortality in persons with colorectal cancer (CRC). We sought to determine the association of pre-diagnosis body mass index (BMI) trajectories on mortality after CRC diagnosis. Methods: Utilizing the Multiethnic Cohort, we included adults aged 18–75 between 1 January 1993 and 1 January 2019 with a diagnosis of CRC and at least three available BMIs. The primary exposure, BMI, was subjected to group-based trajectory modeling (GBTM). We evaluated all-cause and CRC-specific mortality, using Cox proportional hazard (PH) models. Results: Of 924 persons, the median age was 60 years, and 54% were female. There was no statistically significant association between pre-cancer BMI trajectory and either all-cause or cancer-specific mortality. In competing risk analysis, the risk of CRC-specific mortality was higher for African Americans (HR = 1.56, 95% CI [1.00–2.43], p = 0.048) and smokers (HR = 1.59, 95% CI [1.10–2.32], p = 0.015). Risk of all-cause mortality was higher for Hawaiian persons (HR = 2.85, 95% CI [1.31–6.21], p = 0.009) and persons with diabetes (HR = 1.83, 95% CI [1.08–3.10], p = 0.026). Conclusions: Pre-diagnosis BMI trajectories were not associated with mortality after CRC diagnosis, whereas race/ethnicity, diabetes, and smoking were associated with an increased risk of death. Our findings suggest the obesity paradox alone does not account for mortality after CRC diagnosis. [ABSTRACT FROM AUTHOR]

The liver X receptors (LXRs) are members of the nuclear receptor superfamily that regulate sterol metabolism and inflammation. We sought to identify previously unknown genes regulated by LXRs in macrophages and to determine their contribution to atherogenesis. Here we characterize a novel LXR target gene, the lipopolysaccharide binding protein (LBP) gene. Surprisingly, the ability of LXRs to control LBP expression is cell-type specific, occurring in macrophages but not liver. Treatment of macrophages with oxysterols or loading with modified LDL induces LBP in an LXR-dependent manner, suggesting a potential role for LBP in the cellular response to cholesterol overload. To investigate this further, we performed bone marrow transplant studies. After 18 weeks of Western diet feeding, atherosclerotic lesion burden was assessed revealing markedly smaller lesions in the LBP(-/-) recipients. Furthermore, loss of bone marrow LBP expression increased apoptosis in atherosclerotic lesions as determined by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Supporting in vitro studies with isolated macrophages showed that LBP expression does not affect cholesterol efflux but promotes the survival of macrophages in the setting of cholesterol loading. The LBP gene is a macrophage-specific LXR target that promotes foam cell survival and atherogenesis.

The critical height for DNAPL entry into a partially water saturated, dead-end fracture is derived and compared to laboratory observations. Experiments conducted in an analog, parallel-plate fracture demonstrate that DNAPL accumulates above the water until the height of the DNAPL overcomes the sum of the capillary forces at the DNAPL-air interface and at the DNAPL-water interface. These experiments also show that DNAPL preferentially enters the water at locations where DNAPL has previously entered, and the entry heights for these subsequent entries are lower than the heights measured for the initial invasion. The wetting contact angle at the DNAPL-water interface becomes larger at the locations where the DNAPL has already entered the water because of residual DNAPL on the fracture walls, which results in lowering the critical entry height at those locations. The experiments also demonstrate that a DNAPL lens can remain nearly immobile above the water for a period of time before eventually redistributing itself and entering the water.

The Gardner and van Genuchten models of relative permeability are widely used in analytical and numerical solutions to flow problems. However, the applicab ility of the Gardner model to real problems is usually limited, because empirical relative permeability data to calibrate the model are not routinely available. In contrast, van Genuchten parameters can be estimated using more routinely available matric potential and saturation data. However, the van Genuchten model is not amenable to analytical solutions. In this paper, we introduce generalized conversion formulae that reconcile these two models. In general, we find that the Gardner parameter alpha G is related to the van Genuchten parameters alpha vG and n by alpha G=alpha vG ~; 1:3 n. This conversion rule will allow direct recasting of Gardner-based analytical solutions in the van Genuchten parameter space. The validity of the proposed formulae was tested by comparing the predicted relative permeability of various porous media with measured values.

Introduction: Cefazolin is the leading antibiotic used to prevent surgical site infections worldwide. Consensus guidelines recommend adjustment of the cefazolin dose above and below 120 kg without regard to body composition. Algorithms exist to repurpose radiologic data into body composition (morphomics) and inform dosing decisions in obesity. Objectives: To compare the current standard of body weight to morphomic measurements as covariates of cefazolin pharmacokinetics and aid dose stratification of cefazolin in patients with obesity undergoing colorectal surgery. Methods: This prospective study measured cefazolin plasma, fat, and colon tissue concentrations in colorectal surgery patients in order to develop a morphomics‐informed population pharmacokinetic (PopPK) model to guide dose adjustments. A physiologically‐based pharmacokinetic (PBPK) model was also constructed to inform tissue partitioning in morbidly obese patients (n = 21, body mass index ≥35 kg/m2 with one or more co‐morbid conditions). Results: Morphomics and pharmacokinetic data were available in 58 patients with a median [min, max] weight and age of 95.9 [68.5, 148.8] kg and 55 [25, 79] years, respectively. The plasma‐to‐subcutaneous fat partition coefficient was predicted to be 0.072 and 0.060 by the PopPK and PBPK models, respectively. The estimated creatinine clearance (eCLcr) and body depth at the third lumbar vertebra (body depth_L3) were identified as covariates of cefazolin exposure. The probability of maintaining subcutaneous fat concentrations above 2 μg/mL for 100% of a 4‐h surgical period was below 90% when eCLcr ≥105 mL/min and body depth_L3 ≥ 300 mm and less sensitive to the rate of infusion between 5 and 60 min. Conclusions: Kidney function and morphomics were more informative than body weight as covariates of cefazolin target site exposure. Data from more diverse populations, consensus on target cefazolin exposure, and comparative studies are needed before a change in practice can be implemented. [ABSTRACT FROM AUTHOR]

This case describes the marketing strategy and business model of Renoir Inc., a premium jigsaw puzzle retailer which offers high-quality art puzzles and customized framing services. By taking advantage of the IKEA effect associated with puzzles, Renoir sets premium prices, establishes a group of loyal customers, and appropriates better profits. Students are expected to understand the theoretical mechanisms underpinning Renoir's strategy and be able to apply that knowledge to assess the magnitude of the two challenges Renoir encountered during the COVID pandemic: (1) demand decline due to the economic lockdowns, and (2) supply shortage from the premium European puzzle makers. Based on the information provided, students should be able to propose feasible solutions. [ABSTRACT FROM AUTHOR]

This report details the work done between June 13 and September 30, 2006 by Lawrence Berkeley National Laboratory (LBNL) scientists to assist Fermi National Accelerator Laboratory (Fermilab) staff in understanding tritium transport at the Neutrino at the Main Injector (NuMI) facility. As a byproduct of beamline operation, the facility produces (among other components) tritium in engineered materials and the surrounding rock formation. Once the tritium is generated, it may be contained at the source location, migrate to other regions within the facility, or be released to the environment.

A drift shadow is an area immediately beneath an underground void that, in theory, will be relatively drier than the surrounding rock mass. Numerical and analytical models of water flow through unsaturated rock predict the existence of a drift shadow, but field tests confirming its existence have yet to be performed. Proving the existence of drift shadows and understanding their hydrologic and transport characteristics could provide a better understanding of how contaminants move in the subsurface if released from waste emplacement drifts such as the proposed nuclear waste repository at Yucca Mountain, Nevada. We describe the field program that will be used to investigate the existence of a drift shadow and the corresponding hydrological process at the Hazel-Atlas silica-sand mine located at the Black Diamond Mines Regional Preserve in Antioch, California. The location and configuration of this mine makes it an excellent site to observe and measure drift shadow characteristics. The mine is located in a porous sandstone unit of the Domengine Formation, an approximately 230 meter thick series of interbedded Eocene-age shales, coals, and massive-bedded sandstones. The mining method used at the mine required the development of two parallel drifts, one above the other, driven along the strike of the mined sandstone stratum. This configuration provides the opportunity to introduce water into the rock mass in the upper drift and to observe and measure its flow around the underlying drift. The passive and active hydrologic tests to be performed are described. In the passive method, cores will be obtained in a radial pattern around a drift and will be sectioned and analyzed for in-situ water content and chemical constituents. With the active hydrologic test, water will be introduced into the upper drift of the two parallel drifts and the flow of the water will be tracked as it passes near the bottom drift. Tensiometers, electrical resistance probes, neutron probes, and ground penetrating radar may be used to monitor the change in moisture content and potential over time as water is released.

We have carried out numerical simulations of three-dimensional non-isothermal flow around an in situ heat-based flow sensor to investigate how formation heterogeneities can affect the interpretation of ground water flow velocities from this instrument. The flow sensor operates by constant heating of a 0.75 m long, 5 cm diameter cylindrical probe, which contains 30 thermistors in contact with the formation. The temperature evolution at each thermistor can be inverted to obtain an estimate of the ground water flow velocity vector using the standard interpretive method, which assumes that the formation is homogeneous. Analysis of data from heat-based flow sensors installed in a sand aquifer at the Former Fort Ord Army Base near Monterey, California suggested an unexpected component of downward flow. The magnitudes of the vertical velocities were expected to be much less than the horizontal velocities at this site because the sensors were installed just above a clay aquitard. Numerical simulations were conducted to examine how differences in thermal conductivities may lead to spurious indications of vertical flow velocities. We found that a decrease in the thermal conductivity near the bottom of the sensor can perturb the temperature profiles along the instrument in such a manner that analyses assuming homogeneous thermal conductivity could indicate a vertical flow component even though flow is actually horizontal. This work demonstrates how modeling can be used to simulate instrument response to formation heterogeneity, and shows that caution must be used in interpreting data from such devices using overly simplistic assumptions.