Inotropic effects of propofol, thiopental, midazolam, etomidate, and ketamine on isolated human atrial muscle

Background: Cardiovascular instability after intravenous induction of anesthesia may be explained partly by direct negative inotropic effects. The direct inotropic influence of etomidate, ketamine, midazolam, propofol, and thiopental on the contractility of isolated human atrial tissue was determined. Effective concentrations were compared with those reported clinically. Methods: Atrial tissue was obtained from 16 patients undergoing coronary bypass surgery. Each fragment was divided into three strips, and one anesthetic was tested per strip in increasing concentrations (10 -6 to 10 - 2 M). Strips were stimulated at 0.5 Hz, and maximum isometric force was measured. Induction agents were studied in two groups, group 1 (n = 7) containing thiopental, midazolam, and propofol, and group 2 (n = 9) consisting of etomidate, ketamine, and propofol. Results: The tested anesthetics caused a concentration-dependent depression of contractility resulting in complete cessation of contractions at the highest concentrations. The IC 50s (mean ± SEM; μM) for inhibition of the contractility were: thiopental 43 ± 7.6, propofol 235 ± 48 (group 1), and 246 ± 42 (group 2), midazolam 145 ± 54, etomidate 133 ± 13, and ketamine 303 ± 54. Conclusions: This is the first study demonstrating a concentration-dependent negative inotropic effect of intravenous anesthetics in isolated human atrial muscle. NO inhibition of myocardial contractility was found in the clinical concentration ranges of propofol, midazolam, and etomidate. In contrast, thiopental showed strong and ketamine showed slight negative inotropic properties. Thus, negative inotropic effects may explain in part the cardiovascular depression on induction of anesthesia with thiopental but not with propofol, midazolam, and etomidate. Improvement of hemodynamics after induction of anesthesia with ketamine cannot be explained by intrinsic cardiac stimulation

Geobim for digital building permit process: Learning from a case study in Rotterdam

Among the digitalization processes which are being raised in Europe and in the world, the building permit process is seen as one of the priorities by municipalities, governmental institutions and standardization organizations. However, in current practice, the building permit issuing as well as the integration of geoinformation with BIM (GeoBIM) suffers from a number of complex sub-issues. These issues still remain and prevent the development of successful methodologies. In this paper, the building permit use case is explored within a project in close collaboration with the municipality of Rotterdam. A very specific case study in Rotterdam was selected as a starting point, which allowed us to develop the needed methodology for the implementation of an effective tool. In this paper we highlight the interpretation and formalization of regulation for building height, overhang and tower ratio. While these rules are specific to a zoning plan in Rotterdam, we believe that the methodology and encountered issues in formalizing the rules, applying the rules on delivered models and integrating various data sources (BIM and GIS specifically) are general to most building codes

Mouse precision-cut liver slices as an ex vivo model to study drug-induced cholestasis

Drugs are often withdrawn from the market due to the manifestation of drug-induced liver injury (DILI) in patients. Drug-induced cholestasis (DIC), defined as obstruction of hepatic bile flow due to medication, is one form of DILI. Because DILI is idiosyncratic, and the resulting cholestasis complex, there is no suitable in vitro model for early DIC detection during drug development. Our goal was to develop a mouse precision-cut liver slice (mPCLS) model to study DIC and to assess cholestasis development using conventional molecular biology and analytical chemistry methods. Cholestasis was induced in mPCLS through a 48-h-incubation with three drugs known to induce cholestasis in humans, namely chlorpromazine (15, 20, and 30 µM), cyclosporin A (1, 3, and 6 µM) or glibenclamide (25, 50, and 65 µM). A bile-acid mixture (16 µM) that is physiologically representative of the human bile-acid pool was added to the incubation medium with drug, and results were compared to incubations with no added bile acids. Treatment of PCLS with cholestatic drugs increased the intracellular bile-acid concentration of deoxycholic acid and modulated bile-transporter genes. Chlorpromazine led to the most pronounced cholestasis in 48 h, observed as increased toxicity; decreased protein and gene expression of the bile salt export pump; increased gene expression of multidrug resistance-associated protein 4; and accumulation of intracellular bile acids. Moreover, chlorpromazine-induced cholestasis exhibited some transition into fibrosis, evidenced by increased gene expression of collagen 1A1 and heatshock protein 47. In conclusion, we demonstrate that mPCLS can be used to study human DIC onset and progression in a 48 h period. We thus propose this model is suited for other similar studies of human DIC

Algorithms and literate programs for weighted low-rank approximation with missing data

Linear models identification from data with missing values is posed as a weighted low-rank approximation problem with weights related to the missing values equal to zero. Alternating projections and variable projections methods for solving the resulting problem are outlined and implemented in a literate programming style, using Matlab/Octave's scripting language. The methods are evaluated on synthetic data and real data from the MovieLens data sets

Towards a biomimetic gyroscope inspired by the fly's haltere using microelectromechanical systems technology

Flies use so-called halteres to sense body rotation based on Coriolis forces for supporting equilibrium reflexes. Inspired by these halteres, a biomimetic gimbal-suspended gyroscope has been developed using microelectromechanical systems (MEMS) technology. Design rules for this type of gyroscope are derived, in which the haltere-inspired MEMS gyroscope is geared towards a large measurement bandwidth and a fast response, rather than towards a high responsivity. Measurements for the biomimetic gyroscope indicate a (drive mode) resonance frequency of about 550 Hz and a damping ratio of 0.9. Further, the theoretical performance of the fly's gyroscopic system and the developed MEMS haltere-based gyroscope is assessed and the potential of this MEMS gyroscope is discussed

Do neuroendocrine cells in human prostate cancer express androgen receptor?

The presence of androgen receptors (AR) in neuroendocrine cells was investigated in benign tissue of 10 prostatectomy specimens, in 12 prostatic adenocarcinomas with focal neuroendocrine differentiation and in 1 case of a pure neuroendocrine small cell carcinoma of the prostate. Neuroendocrine cells were defined by their reactivity with an antibody to chromogranin A. Monoclonal antibody F39.4 directed against the amino-terminal domain of the AR molecule was used to detect AR. AR and chromogranin A were simultaneously visualized with a double immunofluorescence technique. The results indicate that chromogranin positive cells in both benign and malignant prostatic tissue lack detectable expression of AR. No effect of endocrine therapy was noted. These results are in agreement with the hypothesis that prostatic neuroendocrine tumour cells represent an androgen insensitive cell population, which incidentally may expand to replace the androgen-sensitive tumour cell population during androgen ablation therapy

The consistency between planned and actually given nursing care in long-terminstitutional care

Continuous information exchange between healthcare professionals is facilitated by individualized care plans. Compliance with the planned care as documented in care plans is important to provide person-centered care which contributes to the continuity of care and quality of care outcomes. Using the Nursing Interventions Classification, this study examined the consistency between documented and actually provided interventions by type of nursing staff with 150 residents in long-term institutional care. The consistency was especially high for basic (93%) and complex (79%) physiological care. To a lesser extent for interventions in the behavioral domain (66%). Except for the safety domain, the probability that documented interventions were provided was high for all domains (≥ 91%, p > 0.05). NAs generally provided the interventions as documented. Findings suggest that HCAs worked beyond there scope of practice. The results may have implications for the deployment of nursing staff and are of importance to managers

Projected sea level rise and changes in extreme storm surge and wave events during the 21st century in the region of Singapore

Singapore is an island state with considerable population, industries, commerce and transport located in coastal areas at elevations less than 2 m making it vulnerable to sea-level rise. Mitigation against future inundation events requires a quantitative assessment of risk. To address this need, regional projections of changes in (i) long-term mean sea level and (ii) the frequency of extreme storm surge and wave events have been combined to explore potential changes to coastal flood risk over the 21st century. Local changes in time mean sea level were evaluated using the process-based climate model data and methods presented in the IPCC AR5. Regional surge and wave solutions extending from 1980 to 2100 were generated using ~ 12 km resolution surge (Nucleus for European Modelling of the Ocean – NEMO) and wave (WaveWatchIII) models. Ocean simulations were forced by output from a selection of four downscaled (~ 12 km resolution) atmospheric models, forced at the lateral boundaries by global climate model simulations generated for the IPCC AR5. Long-term trends in skew surge and significant wave height were then assessed using a generalised extreme value model, fit to the largest modelled events each year. An additional atmospheric solution downscaled from the ERA-Interim global reanalysis was used to force historical ocean model simulations extending from 1980–2010, enabling a quantitative assessment of model skill. Simulated historical sea surface height and significant wave height time series were compared to tide gauge data and satellite altimetry data respectively. Central estimates of the long-term mean sea level rise at Singapore by 2100 were projected to be 0.52 m (0.74 m) under the RCP 4.5 (8.5) scenarios respectively. Trends in surge and significant wave height 2 year return levels were found to be statistically insignificant and/or physically very small under the more severe RCP8.5 scenario. We conclude that changes to long-term mean sea level constitute the dominant signal of change to the projected inundation risk for Singapore during the 21st century. We note that the largest recorded surge residual in the Singapore Strait of ~ 84 cm lies between the central and upper estimates of sea level rise by 2100, highlighting the vulnerability of the region