An open source physiologically based kinetic model for the chicken (Gallus gallus domesticus): Calibration and validation for the prediction residues in tissues and eggs.

Xenobiotics from anthropogenic and natural origin enter animal feed and human food as regulated compounds, environmental contaminants or as part of components of the diet. After dietary exposure, a chemical is absorbed and distributed systematically to a range of organs and tissues, metabolised, and excreted. Physiologically based kinetic (PBK) models have been developed to estimate internal concentrations from external doses. In this study, a generic multi-compartment PBK model was developed for chicken. The PBK model was implemented for seven compounds (with log Kow range −1.37–6.2) to quantitatively link external dose and internal dose for risk assessment of chemicals. Global sensitivity analysis was performed for a hydrophilic and a lipophilic compound to identify the most sensitive parameters in the PBK model. Model predictions were compared to measured data according to dataset-specific exposure scenarios. Globally, 71% of the model predictions were within a 3-fold change of the measured data for chicken and only 7% of the PBK predictions were outside a 10-fold change. While most model input parameters still rely on in vivo experiments, in vitro data were also used as model input to predict internal concentration of the coccidiostat monensin. Future developments of generic PBK models in chicken and other species of relevance to animal health risk assessment are discussed. Keywords: Risk assessment, Chicken, Physiologically based kinetic model, In vitro to in vivo extrapolation, Global sensitivity analysi

Laparoscopic Adjustable Gastric Banding and Hypoglycemia

Obesity is commonplace, and surgical treatment usually includes Roux-en-Y gastric bypasses (RYGBs). RYGBs have the most documented side effects including vitamin deficiencies, rebound weight gain, and symptomatic hypoglycemia; fewer series exist describing hypoglycemia following other bariatric operations. We reviewed all patients undergoing laparoscopic adjustable gastric banding (LAGB) at our institution between 2008 and 2012. Three patients were identified to have symptomatic hypoglycemia following LAGB. Mean time from surgery was 33 months (range 14–45 months), and mean weight loss was 32.7 kg (range 15.9–43.1 kg). None of the patients had preexisting diabetes. Therefore, symptomatic hypoglycemia should be investigated irrespective of bariatric operation

Theory of monolayers with boundaries: Exact results and Perturbative analysis

Domains and bubbles in tilted phases of Langmuir monolayers contain a class of textures knows as boojums. The boundaries of such domains and bubbles may display either cusp-like features or indentations. We derive analytic expressions for the textures within domains and surrounding bubbles, and for the shapes of the boundaries of these regions. The derivation is perturbative in the deviation of the bounding curve from a circle. This method is not expected to be accurate when the boundary suffers large distortions, but it does provide important clues with regard to the influence of various energetic terms on the order-parameter texture and the shape of the domain or bubble bounding curve. We also look into the effects of thermal fluctuations, which include a sample-size-dependent effective line tension.Comment: replaced with published version, 21 pages, 16 figures include

Human variability in influx and efflux transporters in relation to uncertainty factors for chemical risk assessment

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Bayesian meta-analysis of inter-phenotypic differences in human serum paraoxonase-1 activity for chemical risk assessment

Human variability in paraoxonase-1 (PON1) activities is driven by genetic polymorphisms that affect the internal dose of active oxons of organophosphorus (OP) insecticides. Here, an extensive literature search has been performed to collect human genotypic frequencies (i.e. L55M, Q192R, and C-108T) in subgroups from a range of geographical ancestry and PON1 activities in three probe substrates (paraoxon, diazoxon and phenyl acetate). Bayesian meta-analyses were performed to estimate variability distributions for PON1 activities and PON1-related uncertainty factors (UFs), while integrating quantifiable sources of inter-study, inter-phenotypic and inter-individual differences. Inter-phenotypic differences were quantified using the population with high PON1 activity as the reference group. Results from the meta-analyses provided PON1 variability distributions and these can be implemented in generic physiologically based kinetic models to develop quantitative in vitro in vivo extrapolation models. PON1-related UFs in the Caucasian population were above the default toxicokinetic UF of 3.16 for two specific genotypes namely −108CC using diazoxon as probe substrate and, −108CT, −108TT, 55MM and 192QQ using paraoxon as probe substrate. However, integration of PON1 genotypic frequencies and activity distributions showed that all UFs were within the default toxicokinetic UF. Quantitative inter-individual differences in PON1 activity are important for chemical risk assessment particularly with regards to the potential sensitivity to organophosphates' toxicity. Keywords: Human variability, PON1 activity, Polymorphism, Uncertainty facto

LPMLE3 : a novel 1-D approach to study water flow in streambeds using heat as a tracer

We introduce LPMLE3, a new 1-D approach to quantify vertical water flow components at streambeds using temperature data collected in different depths. LPMLE3 solves the partial differential equation for coupled water flow and heat transport in the frequency domain. Unlike other 1-D approaches it does not assume a semi-infinite halfspace with the location of the lower boundary condition approaching infinity. Instead, it uses local upper and lower boundary conditions. As such, the streambed can be divided into finite subdomains bound at the top and bottom by a temperature-time series. Information from a third temperature sensor within each subdomain is then used for parameter estimation. LPMLE3 applies a low order local polynomial to separate periodic and transient parts (including the noise contributions) of a temperature-time series and calculates the frequency response of each subdomain to a known temperature input at the streambed top. A maximum-likelihood estimator is used to estimate the vertical component of water flow, thermal diffusivity, and their uncertainties for each streambed subdomain and provides information regarding model quality. We tested the method on synthetic temperature data generated with the numerical model STRIVE and demonstrate how the vertical flow component can be quantified for field data collected in a Belgian stream. We show that by using the results in additional analyses, nonvertical flow components could be identified and by making certain assumptions they could be quantified for each subdomain. LPMLE3 performed well on both simulated and field data and can be considered a valuable addition to the existing 1-D methods

River-aquifer interactions in a semiarid environment investigated using point and reach measurements

A critical hydrological process is the interaction between rivers and aquifers. However, accurately determining this interaction from one method alone is difficult. At a point, the water exchange in the riverbed can be determined using temperature variations over depth. Over the river reach, differential gauging can be used to determine averaged losses or gains. This study combines these two methods and applies them to a 34 km reach of a semiarid river in eastern Australia under highly transient conditions. It is found that high and low river flows translate into high and low riverbed Darcy fluxes, and that these are strongly losing during high flows, and only slightly losing or gaining for low flows. The spatial variability in riverbed Darcy fluxes may be explained by riverbed heterogeneity, with higher variability at greater spatial scales. Although the river-aquifer gradient is the main driver of riverbed Darcy flux at high flows, considerable uncertainty in both the flux magnitude and direction estimates were found during low flows. The reach-scale results demonstrate that high-flow events account for 64% of the reach loss (or 43% if overbank events are excluded) despite occurring only 11% of the time. By examining the relationship between total flow volume, river stage and duration for in-channel flows, we find the loss ratio (flow loss/total flow) can be greater for smaller flows than larger flows with similar duration. Implications of the study for the modeling and management of connected water resources are also discussed. Key Points Losing riverbed fluxes under high flows and approximately neutral under low flows Event driven riverbed fluxes dominate reach losses Smaller events can have higher loss ratio than larger event

Economic predictors of differences in interview faking between countries : economic inequality matters, not the state of economy

Many companies recruit employees from different parts of the globe, and faking behavior by potential employees is a ubiquitous phenomenon. It seems that applicants from some countries are more prone to faking compared to others, but the reasons for these differences are largely unexplored. This study relates country-level economic variables to faking behavior in hiring processes. In a cross-national study across 20 countries, participants (N = 3839) reported their faking behavior in their last job interview. This study used the random response technique (RRT) to ensure participants anonymity and to foster honest answers regarding faking behavior. Results indicate that general economic indicators (gross domestic product per capita [GDP] and unemployment rate) show negligible correlations with faking across the countries, whereas economic inequality is positively related to the extent of applicant faking to a substantial extent. These findings imply that people are sensitive to inequality within countries and that inequality relates to faking, because inequality might actuate other psychological processes (e.g., envy) which in turn increase the probability for unethical behavior in many forms

Anthropometric, biochemical and clinical assessment of malnutrition in Malaysian patients with advanced cirrhosis

<p>Abstract</p> <p>Background</p> <p>There is limited data on the nutritional status of Asian patients with various aetiologies of cirrhosis. This study aimed to determine the prevalence of malnutrition and to compare nutritional differences between various aetiologies.</p> <p>Methodology</p> <p>A cross-sectional study of adult patients with decompensated cirrhosis was conducted. Nutritional status was assessed using standard anthropometry, serum visceral proteins and subjective global assessment (SGA).</p> <p>Results</p> <p>Thirty six patients (mean age 59.8 ± 12.8 years; 66.7% males; 41.6% viral hepatitis; Child-Pugh C 55.6%) with decompensated cirrhosis were recruited. Malnutrition was prevalent in 18 (50%) patients and the mean caloric intake was low at 15.2 kcal/kg/day. SGA grade C, as compared to SGA grade B, demonstrated significantly lower anthropometric values in males (BMI 18.1 ± 1.6 vs 26.3 ± 3.5 kg/m2, p < 0.0001; MAMC 19.4 ± 1.5 vs 24.5 ± 3.6 cm, p = 0.002) and females (BMI 19.4 ± 2.7 vs 28.9 ± 4.3, p = 0.001; MAMC 18.0 ± 0.9 vs 28.1 ± 3.6, p < 0.0001), but not with visceral proteins. The SGA demonstrated a trend towards more malnutrition in Child-Pugh C compared to Child-Pugh B liver cirrhosis (40% grade C vs 25% grade C, p = 0.48). Alcoholic cirrhosis had a higher proportion of SGA grade C (41.7%) compared to viral (26.7%) and cryptogenic (28.6%) cirrhosis, but this was not statistically significant.</p> <p>Conclusion</p> <p>Significant malnutrition in Malaysian patients with advanced cirrhosis is common. Alcoholic cirrhosis may have more malnutrition compared to other aetiologies of cirrhosis.</p

Different degrees of malnutrition and immunological alterations according to the aetiology of cirrhosis: a prospective and sequential study

OBJECTIVES: In this work we investigated how immunological dysfunction and malnutrition interact in alcoholic and viral aetiologies of cirrhosis. METHODS: To investigate the matter, 77 cirrhotic patients divided in three aetiologies [Alcohol, HCV and Alcohol + HCV) and 32 controls were prospectivelly and sequentially studied. Parameters of humoral immunity (Components 3 and 4 of seric complement and immunoglobulins A M, G and E) and of cellular immunity (total leukocytes and lymphocytes in peripheral blood, T lymphocytes subpopulations, CD4+ and CD8+, CD4+/CD8+ ratio and intradermic tests of delayed hypersensitivity), as well as nutrititional parameters: anthropometric measures, serum albumin and transferrin were evaluated. RESULTS: Multiple statistical comparisons showed that IgM was higher in HCV group; IgG was significantly elevated in both HCV and Alcohol + HCV, whereas for the Alcohol group, IgE was found at higher titles. The analysis of T- lymphocytes subpopulations showed no aetiologic differences, but intradermic tests of delayed hypersensitivity did show greater frequency of anergy in the Alcohol group. For anthropometric parameters, the Alcohol +HCV group displayed the lowest triceps skinfold whereas creatinine – height index evaluation was more preserved in the HCV group. Body mass index, arm muscle area and arm fat area showed that differently from alcohol group, the HCV group was similar to control. CONCLUSION: Significant differences were found among the main aetiologies of cirrhosis concerning immunological alterations and nutritional status: better nutrition and worse immunology for HCV and vice-versa for alcohol