•Several load estimation techniques are evaluated using temporally dense water-quality data.•Most methods provide accurate estimates of major ions and total nitrogen.•Reduced accuracy is observed for ...nitrate, total phosphorus and sediment loads.•Beale’s ratio estimator and WRTDS generally exhibit greater estimation accuracy and lower bias.
Effective management of water resources requires accurate information on the mass, or load of water-quality constituents transported from upstream watersheds to downstream receiving waters. Despite this need, no single method has been shown to consistently provide accurate load estimates among different water-quality constituents, sampling sites, and sampling regimes. We evaluate the accuracy of several load estimation methods across a broad range of sampling and environmental conditions. This analysis uses random sub-samples drawn from temporally-dense data sets of total nitrogen, total phosphorus, nitrate, and suspended-sediment concentration, and includes measurements of specific conductance which was used as a surrogate for dissolved solids concentration. Methods considered include linear interpolation and ratio estimators, regression-based methods historically employed by the U.S. Geological Survey, and newer flexible techniques including Weighted Regressions on Time, Season, and Discharge (WRTDS) and a generalized non-linear additive model. No single method is identified to have the greatest accuracy across all constituents, sites, and sampling scenarios. Most methods provide accurate estimates of specific conductance (used as a surrogate for total dissolved solids or specific major ions) and total nitrogen – lower accuracy is observed for the estimation of nitrate, total phosphorus and suspended sediment loads. Methods that allow for flexibility in the relation between concentration and flow conditions, specifically Beale’s ratio estimator and WRTDS, exhibit greater estimation accuracy and lower bias. Evaluation of methods across simulated sampling scenarios indicate that (1) high-flow sampling is necessary to produce accurate load estimates, (2) extrapolation of sample data through time or across more extreme flow conditions reduces load estimate accuracy, and (3) WRTDS and methods that use a Kalman filter or smoothing to correct for departures between individual modeled and observed values benefit most from more frequent water-quality sampling.
Gallbladder cancer (GBC) is one of the most common and aggressive biliary tract cancers with a dismal prognosis. Ongoing clinical trials are evaluating a few selected immune checkpoint inhibitors ...(ICIs) as monotherapy for the treatment of GBC patients. However, only a subset of patients benefits from these treatments. To improve ICI therapy response, molecular mechanisms that confer resistance to immune checkpoint (IC) blockade needs to be explored. Epithelial-to-mesenchymal transition (EMT) program and cancer stem cells (CSCs) have been implicated as key processes that confer ICI treatment resistance. However, in GBC the EMT-CSC-IC axis has not yet been clearly elucidated. This study aims to examine the aberrant expression of ICs associated with CSC and EMT. We successfully enriched CSCs by utilizing a 3-dimensional culture system and established a reversible EMT model with human GBC NOZ cell line. Notably, ICs CD73 and PD-L1 were closely associated with both CSC and EMT phenotypes. Knockdown of CD73 or PD-L1 reduced the proliferative and motile abilities of both adherent monolayers and anchorage-free spheroids. In conclusion, blocking CD73 and PD-L1 offer a promising therapeutic strategy for targeting highly aggressive populations with CSC and EMT phenotype to improve GBC patient prognosis.
Introduction
Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths both globally and in Australia. Surveillance for HCC in at‐risk populations allows diagnosis at an early stage, when ...potentially curable. However, most Australians diagnosed with HCC die of the cancer or of liver disease. In the changing landscape of HCC management, unique challenges may lead to clinical practice variation. As a result, there is a need to identify best practice management of HCC in an Australian context. This consensus statement has been developed for health professionals involved in the care of adult patients with HCC in Australia. It is applicable to specialists, general medical practitioners, nurses, health coordinators and hospital administrators.
Methods and recommendations
This statement has been developed by specialists in hepatology, radiology, surgery, oncology, palliative care, and primary care, including medical practitioners and nurses. The statement addresses four main areas relevant to HCC management: epidemiology and incidence, diagnosis, treatment, and patient management.
A modified Delphi process was used to reach consensus on 31 recommendations. Principal recommendations include the adoption of surveillance strategies, use of multidisciplinary meetings, diagnosis, treatment options and patient management.
Changes in management as a result of this statement
This consensus statement will simplify HCC patient management and reduce clinical variation. Ultimately, this should result in better outcomes for patients with HCC.
Our study extends and enhances entrepreneurial action theory (EAT) by considering the strategic advantage or disadvantage of impulsive action. To date, EAT has largely sidestepped the role of ...dispositional impulsivity, limiting its veridicality and inclusivity. Popularized notions of celebrity entrepreneurs and an increasingly large body of empirical research on the prevalence of impulsivity have inspired a reassessment of what drives entrepreneurs. Looking beyond both the anecdotes and well-established prevalence of impulsivity, we develop and illustrate a novel theory concerning the fate of impulsive nascent entrepreneurs who are wired for nondeliberative, less-calculative action. We use an agent-based model and conduct simulation-based experiments involving 2.7 million virtual entrepreneurs to identify and explicate the specific conditions under which impulsivity does or does not generate strategic advantage. Accordingly, we contribute a broader and deeper theorization of EAT, taking notable steps toward the inclusion of nontraditional entrepreneurs and the varied impacts of impulsive action in this domain’s evolving conception of new venture emergence.
The rate at which genomes diverge during speciation is unknown, as are the physical dynamics of the process. Here, we compare full genome sequences of 32 butterflies, representing five species from a ...hybridizing Heliconius butterfly community, to examine genome-wide patterns of introgression and infer how divergence evolves during the speciation process. Our analyses reveal that initial divergence is restricted to a small fraction of the genome, largely clustered around known wing-patterning genes. Over time, divergence evolves rapidly, due primarily to the origin of new divergent regions. Furthermore, divergent genomic regions display signatures of both selection and adaptive introgression, demonstrating the link between microevolutionary processes acting within species and the origin of species across macroevolutionary timescales. Our results provide a uniquely comprehensive portrait of the evolving species boundary due to the role that hybridization plays in reducing the background accumulation of divergence at neutral sites.
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•Speciation with gene flow in Heliconius generates genomic heterogeneity in divergence•Initial divergence is highly restricted, largely clustered on wing-patterning genes•Divergence evolves rapidly due to newly differentiated regions of the genome•Process influenced by divergent and purifying selection as well as introgression
The rate at which genomes diverge during speciation is unknown, as are the physical dynamics of the process. Here, Kronforst, Mullen, and colleagues compare 32 genomes, spanning a hybridizing Heliconius butterfly community in Costa Rica, to show that divergence is initially highly restricted to just wing-patterning genes but then expands rapidly across the genome. Genome evolution during speciation derives from a dynamic interplay between divergent and purifying selection as well as ongoing gene flow among new species.
This study presents microstructure and mechanical property relationships of cold-sprayed 7075 aluminum during non-isothermal annealing. Microstructure evolution during non-isothermal annealing from ...room temperature to 450°C was performed using in-situ heating via a hot-stage transmission electron microscope. Additional characterization was performed using differential scanning calorimetry and X-ray diffraction. Grain size, dislocation density, microstrain, lattice parameter, and precipitation phenomena were evaluated as a function of annealing temperature. The results showed that cold spray processing accelerated the precipitation kinetics of strengthening phases in the microstructure, compared to the as-received cold spray powder, but did not affect the overall precipitation sequence. Also, pancaked grain structures, found at particle–particle interfaces within the deposition, were converted, due to recrystallization, to ultrafine-grained structures during annealing. The ultrafine-grained structures experienced limited grain growth during the annealing process. This was attributed to the nucleation of grain boundary precipitates in the as-sprayed material, primarily originating from grain boundary solute segregation present in the cold spray powder. Mechanical properties were evaluated using microhardness testing, after annealing, and correlated with microstructural analysis. When subjected to low temperature annealing (below 370°C), the cold spray processed material had a lower microhardness than that found in conventional 7075 aluminum subjected to the same thermal treatment, due to the presence of inter-particle porosity in the cold spray microstructure. Annealing at temperatures above 370°C, however, resulted in an increase in hardness, likely due to a reduction in inter-particle porosity and grain boundary strengthening associated with the retention of an ultrafine grain structure at high temperatures.
•Non-isothermal annealing of cold sprayed 7075 Al depositions from RT to 450°C•Substantial microstructural changes in the pancaked interface regions•Accelerated precipitation kinetics by CS in the deposition compared to the powder•Low hardness of the deposition in less than 370°C due to the presence of porosity•Substantially higher hardness of deposition above 370°C due to GB strengthening
We report on the performance enhancement of 250-nm gate-length H-diamond FETs through thermal treatment of devices at 400 °C and the incorporation of V 2 O 5 as a surface electron acceptor layer. ...Encapsulation of the H-diamond surface with V 2 O 5 is found to increase the transfer doping efficiency and reduce the device access resistance. A reduction in ohmic contact resistance and channel resistance beneath the gate after thermal treatment at 400 °C was found to further reduce the device ON-resistance and increase the maximum drain current and peak transconductance. These devices demonstrate the highest drain current (375 mA/mm) and transconductance (98 mS/mm), yet reported for H-diamond FETs of this gate length that incorporate an electron acceptor oxide layer.
We challenge a stream of thought that focuses on drawing what we see as a frivolous contrast between creation and discovery view of entrepreneurship. Its detachment from the empirical world is ...tantamount to theoretical “fetishism”. We see opportunities as emergent structures, with ontologically real components, epistemologically real functional relationships, and requiring real human actions and interactions to come to fruition. This calls for building theory based on the strengths of both discovery and creation assumptions.
Fundamental research in physics has long been a prerequisite for computer scientists and engineers to design innovative products, such as laptops and cell phones. Technological innovations and ...fundamental research are both part of the so-called STEM fields (Science, Technology, Engineering, and Mathematics), which are known to substantially contribute to economic growth. However, the questions still remain: how much contribution do these fields make to both wealth accumulation and inequality at different levels of analysis? First, analyzing the lists of world’s wealthiest individuals, the Zipf plot analysis demonstrates that STEM billionaires contribute more to wealth inequality than their non-STEM counterparts. Analyzing the companies in the S&P500, we find that STEM firms contribute more to wealth inequality and have larger growth rates on average than the non-STEM firms. Finally, we show that the more STEM graduates in a country, the larger its GDP growth rate. In combination, we demonstrate that STEM is a fractal mechanism that drives wealth accumulation—and the wealth inequality— at different scales of economy—from individual wealth to firm valuation to country GDP.
In the direct-acting antiviral (DAA) era for hepatitis C virus (HCV) infection, sustained virological response (SVR) is very high, but close attention must be paid to the possible occurrence of ...hepatocellular carcinoma (HCC) and reactivation of hepatitis B virus (HBV) in patients with co-infection who achieved SVR in short term. HCC occurrence was more often observed in patients
with
previous HCC history. We found occurrence of HCC in 178 (29.6%) of 602 patients
with
previous HCC history (15.4 months mean follow-up post-DAA initiation) but, in contrast, in only 604 (1.3%) of 45,870 patients
without
previous HCC history (18.2 months mean follow-up). Thus, in these guidelines, we recommend the following: in patients
with
previous HCC history, surveillance at 4-month intervals for HCC by ultrasonography (US) and tumor markers should be performed. In patients
without
previous HCC history, surveillance at 6- to 12-month intervals for HCC including US is recommended until the long-term DAA treatment effects, especially for the resolution of liver fibrosis, are confirmed. This guideline also includes recommendations on how to follow-up patients who have been infected with both HCV and HBV. When HCV was eradicated in these HBsAg-positive patients or patients
with
previous HBV infection (anti-HBc and/or anti-HBs-positive), it was shown that HBV reactivation or HBV DNA reappearance was observed in 67 (41.4%) of 162 or 12 (0.9%) of 1317, respectively. For these co-infected patients, careful attention should be paid to HBV reactivation for 24 weeks post-treatment.
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