2,015 research outputs found
Water Security in Three Major Industries
Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchiv
Revisiting hydro-ecological impacts of climate change on a restored floodplain wetland via hydrological / hydraulic modelling and the UK Climate Projections 2018 scenarios
The hydro-ecological impacts of 40 UK Climate Projections 2018 scenarios on a restored lowland England river floodplain are assessed using a MIKE SHE / MIKE 11 model. Annual precipitation declines for 60% of scenarios (range: -26%–21%, with small, <5%, declines for the central probability level). Potential evapotranspiration increases for all probability levels except the most extreme, very unlikely, 10% level (range: -4%–43%, central probability 9%–20%) Mean, peak and low river discharges are reduced for all but the extreme 90% probability level. Reduced frequency of bankfull discharge dominates (at least halved for the central probability level). Floodplain inundation declines for over 97% of 320 scenario-events. Winter water table levels still intercept the surface, while mean and summer low levels are reduced. Declines in mean summer floodplain water table levels for the central probability level (0.22 m and 0.28 m for the 2050s and 2080s, respectively) are twice as large as those in the more dynamic riparian area. Declines reach 0.39 m for some 10% probability level scenarios. Simulated hydrological changes differ subtly from a previous assessment using earlier UK climate projections. A soil aeration stress index demonstrates that, under baseline conditions, prolonged high winter floodplain water tables drive long periods of low root-zone oxygen, in turn favouring vegetation communities adapted to waterlogged conditions. Climate change reduces aeration stress and the extent of appropriate conditions for these plant communities in favour of communities less tolerant of wet conditions
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Everolimus Exposure as a Predictor of Toxicity in Renal Cell Cancer Patients in the Adjuvant Setting: Results of a Pharmacokinetic Analysis for SWOG S0931 (EVEREST), a Phase III Study (NCT01120249).
BackgroundS0931 is assessing recurrence-free survival in renal cell carcinoma (RCC) patients randomized to receive everolimus (EVE) versus placebo for one year following nephrectomy. Due to a higher than expected dropout rate, we assessed EVE trough levels in the adjuvant setting to evaluate the relationship between EVE exposure and probability of toxicity.MethodsPatients received 10 mg daily EVE for nine 6-week cycles. Pre-dose whole blood samples were collected pre-cycle 2 and pre-cycle 3 and analyzed for EVE. Patients with pre-cycle 2 and/or pre-cycle 3 EVE results were used in the analysis. Patients were segregated into quartiles (Q) based on EVE levels and logistic regression was used to model the most common adverse event outcomes using EVE trough as a predictor. Hazard and odds ratios were adjusted for age, BMI and performance status.ResultsA total of 467 patients were included in this analysis. Quartiles normalized to an EVE dose of 10 mg/day were < 9.0, 9.0-12.9, 12.9-22.8, and > 22.8 ng/mL, respectively. EVE trough levels increased with increasing age (p < 0.001). Furthermore, EVE trough levels were higher in men than women (19.4 versus 15.4 ng/mL, p = 0.01). Risk of grade 2 + triglycerides was increased in Q2 and Q3 vs Q1 (OR = 2.08; p = 0.02 and OR = 2.63; p = 0.002). Risk of grade 2 + rash was increased in Q2 and Q4 vs Q1 (OR = 2.99; p = 0.01 and OR = 2.90; p = 0.02). There was also an increased risk of any grade 3 + tox in Q2 vs Q1 (OR = 1.71; p = 0.05).ConclusionsWe identified significant gender and age-related differences in EVE trough levels in patients receiving adjuvant treatment for RCC. Furthermore, our analysis identified significant associations between EVE exposure and probability of toxicity
Dissociating Statistically Determined Normal Cognitive Abilities and Mild Cognitive Impairment Subtypes with DCTclock.
OBJECTIVE: To determine whether the DCTclock can detect differences across groups of patients seen in the memory clinic for suspected dementia.
METHOD: Patients (n = 123) were classified into the following groups: cognitively normal (CN), subtle cognitive impairment (SbCI), amnestic cognitive impairment (aMCI), and mixed/dysexecutive cognitive impairment (mx/dysMCI). Nine outcome variables included a combined command/copy total score and four command and four copy indices measuring drawing efficiency, simple/complex motor operations, information processing speed, and spatial reasoning.
RESULTS: Total combined command/copy score distinguished between groups in all comparisons with medium to large effects. The mx/dysMCI group had the lowest total combined command/copy scores out of all groups. The mx/dysMCI group scored lower than the CN group on all command indices (
CONCLUSIONS: These results suggest that DCTclock command/copy parameters can dissociate CN, SbCI, and MCI subtypes. The larger effect sizes for command clock indices suggest these metrics are sensitive in detecting early cognitive decline. Additional research with a larger sample is warranted
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Risk Prediction Models for Colorectal Cancer Incorporating Common Genetic Variants: A Systematic Review.
Colorectal cancer screening reduces colorectal cancer incidence and mortality. Risk models based on phenotypic variables have relatively good discrimination in external validation and may improve efficiency of screening. Models incorporating genetic variables may perform better. In this review, we updated our previous review by searching Medline and EMBASE from the end date of that review (January 2014) to February 2019 to identify models incorporating at least one SNP and applicable to asymptomatic individuals in the general population. We identified 23 new models, giving a total of 29. Of those in which the SNP selection was on the basis of published genome-wide association studies, in external or split-sample validation the AUROC was 0.56 to 0.57 for models that included SNPs alone, 0.61 to 0.63 for SNPs in combination with other risk factors, and 0.56 to 0.70 when age was included. Calibration was only reported for four. The addition of SNPs to other risk factors increases discrimination by 0.01 to 0.06. Public health modeling studies suggest that, if determined by risk models, the range of starting ages for screening would be several years greater than using family history alone. Further validation and calibration studies are needed alongside modeling studies to assess the population-level impact of introducing genetic risk-based screening programs
Comparability of neuraminidase inhibition antibody titers measured by enzyme-linked lectin assay (ELLA) for the analysis of influenza vaccine immunogenicity
AbstractNeuraminidase-inhibition (NI) antibody titers can be used to evaluate the immunogenicity of inactivated influenza vaccines and have provided evidence of serologic cross-reactivity between seasonal and pandemic H1N1 viruses. The traditional thiobarbituric acid assay is impractical for large serologic analyses, and therefore many laboratories use an enzyme-linked lectin assay (ELLA) to determine serum NI antibody titers. The comparability of ELLA NI antibody titers when measured in different laboratories was unknown. Here we report a study conducted through the Consortium for the Standardisation of Influenza SeroEpidemiology (CONSISE) to evaluate the variability of the ELLA. NI antibody titers of a set of 12 samples were measured against both N1 and N2 neuraminidase antigens in 3 independent assays by each of 23 laboratories. For a sample repeated in the same assay, ≥96% of N1 and N2 assays had less than a 4-fold difference in titer. Comparison of the titers measured in assays conducted on 3 different days in the same laboratory showed that a four-fold difference in titer was uncommon. Titers of the same sera measured in different laboratories spanned 3 to 6 two-fold dilutions (i.e., 8–64 fold difference in titer), with an average percent geometric coefficient of variation (%GCV) of 112 and 82% against N1 and N2 antigens, respectively. The difference in titer as indicated by fold range and %GCV was improved by normalizing the NI titers to a standard that was included in each assay. This study identified background signal and the amount of antigen in the assay as critical factors that influence titer, providing important information toward development of a consensus ELLA protocol
Interspecies competition in oral biofilms mediated by Streptococcus gordonii extracellular deoxyribonuclease SsnA
Abstract Extracellular DNA (eDNA) is a key component of many microbial biofilms including dental plaque. However, the roles of extracellular deoxyribonuclease (DNase) enzymes within biofilms are poorly understood. Streptococcus gordonii is a pioneer colonizer of dental plaque. Here, we identified and characterised SsnA, a cell wall-associated protein responsible for extracellular DNase activity of S. gordonii. The SsnA-mediated extracellular DNase activity of S. gordonii was suppressed following growth in sugars. SsnA was purified as a recombinant protein and shown to be inactive below pH 6.5. SsnA inhibited biofilm formation by Streptococcus mutans in a pH-dependent manner. Further, SsnA inhibited the growth of oral microcosm biofilms in human saliva. However, inhibition was ameliorated by the addition of sucrose. Together, these data indicate that S. gordonii SsnA plays a key role in interspecies competition within oral biofilms. Acidification of the medium through sugar catabolism could be a strategy for cariogenic species such as S. mutans to prevent SsnA-mediated exclusion from biofilms
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External Validation of Risk Prediction Models Incorporating Common Genetic Variants for Incident Colorectal Cancer Using UK Biobank.
The aim of this study was to compare and externally validate risk scores developed to predict incident colorectal cancer that include common genetic variants (SNPs), with or without established lifestyle/environmental (questionnaire-based/classical/phenotypic) risk factors. We externally validated 23 risk models from a previous systematic review in 443,888 participants ages 37 to 73 from the UK Biobank cohort who had 6-year prospective follow-up, no prior history of colorectal cancer, and data for incidence of colorectal cancer through linkage to national cancer registries. There were 2,679 (0.6%) cases of incident colorectal cancer. We assessed model discrimination using the area under the operating characteristic curve (AUC) and relative risk calibration. The AUC of models including only SNPs increased with the number of included SNPs and was similar in men and women: the model by Huyghe with 120 SNPs had the highest AUC of 0.62 [95% confidence interval (CI), 0.59-0.64] in women and 0.64 (95% CI, 0.61-0.66) in men. Adding phenotypic risk factors without age improved discrimination in men but not in women. Adding phenotypic risk factors and age increased discrimination in all cases (P < 0.05), with the best performing models including SNPs, phenotypic risk factors, and age having AUCs between 0.64 and 0.67 in women and 0.67 and 0.71 in men. Relative risk calibration varied substantially across the models. Among middle-aged people in the UK, existing polygenic risk scores discriminate moderately well between those who do and do not develop colorectal cancer over 6 years. Consideration should be given to exploring the feasibility of incorporating genetic and lifestyle/environmental information in any future stratified colorectal cancer screening program
Vegetable diversity in relation with subclinical atherosclerosis and 15-year atherosclerotic vascular disease deaths in older adult women
Increasing vegetable intake and diversity are recommended to maintain better health. Evidence for the health benefits of vegetable diversity, separate from total intake, is scarce. We aimed to investigate the associations of vegetable diversity with subclinical measures of atherosclerosis and atherosclerotic vascular disease (ASVD) mortality
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