Limited access orders in the developing world :a new approach to the problems of development

The upper-income, advanced industrial countries of the world today all have market economies with open competition, competitive multi-party democratic political systems, and a secure government monopoly over violence. Such open access orders, however, are not the only norm and equilibrium type of society. The middle and low-income developing countries today, like all countries before about 1800, can be understood as limited access orders that maintain their equilibrium in a fundamentally different way. In limited access orders, the state does not have a secure monopoly on violence, and society organizes itself to control violence among the elite factions. A common feature of limited access orders is that political elites divide up control of the economy, each getting some share of the rents. Since outbreaks of violence reduce the rents, the elite factions have incentives to be peaceable most of the time. Adequate stability of the rents and thus of the social order requires limiting access and competition-hence a social order with a fundamentally different logic than the open access order. This paper lays out such a framework and explores some of its implications for the problems of development today.Corporate Law,Labor Policies,Public Sector Corruption&Anticorruption Measures,E-Business,Disability

The IT framework of the European Archive of Historical Earthquake Data (AHEAD)

The European Archive of Historical EArthquake Data (AHEAD) has been developed in the frame of the EC project NERIES and maintained in the frame of the EC project SHARE.AHEAD makes available on the web the result of a networked historical earthquake data research, formalised in terms of studies (papers, reports, macroseismic data points, etc). It provides an updated wealth of data that are unique for many European events in the time-window 1000-1963.A series of IT solutions have been developed in order to support both the research and the networking activities carried out within the building process of AHEAD. The resulting framework is an equally balanced effort in both the back-end and front-end design and implementation, a key feature in a research approach very much human-centred, where the quantity of data is small if compared to terabytes of instrumental data.AHEAD is composed of five mutually dependent data-components: 1) the “Digital Library”, where all the historical earthquake studies are stored and described by bibliographical metadata, 2) the “Consensus Earthquake Inventory”, where the relevant macroseismic data (event date, epicentral area, number of macroseismic data-point, maximum observed intensity) are extrapolated, the best available information are selected and fake earthquakes are highlighted, 3) the “European Macroseismic Database”, where all the available macroseismic data-points (MDPs) are stored, 4) the “Parameters Laboratory”, where earthquakes parameterisation methods are applied to MDPs in order to obtain epicentral locations and magnitudes and 5) the “European Earthquake Catalogue”.The presentation will demonstrate the adopted IT solutions separately for the back-end and the front-end, both for the access-restricted website and the general-purpose implementation designed to be included in the “Earthquake Data Portal”, developed within the EC project NERIES, which targets a much broader scientific community

Influence of renal replacement modalities on amikacin population pharmacokinetics in critically ill patients on continuous renal replacement therapy

The objective of this study was to describe amikacin pharmacokinetics (PK) in critically ill patients receiving equal doses (30 ml/kg of body weight/h) of continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration (CVVHDF). Patients receiving amikacin and undergoing CVVH or CVVHDF were eligible. Population pharmacokinetic analysis and Monte Carlo simulation were undertaken using the Pmetrics software package for R. Sixteen patients (9 undergoing CVVH, 11 undergoing CVVHDF) and 20 sampling intervals were analyzed. A two-compartment linear model best described the data. Patient weight was the only covariate that was associated with drug clearance. The mean +/- standard deviation parameter estimates were 25.2 +/- 17.3 liters for the central volume, 0.89 +/- 1.17 h(-1) for the rate constant for the drug distribution from the central to the peripheral compartment, 2.38 +/- 6.60 h(-1) for the rate constant for the drug distribution from the peripheral to the central compartment, 4.45 +/- 2.35 liters/h for hemodiafiltration clearance, and 4.69 +/- 2.42 liters/h for hemofiltration clearance. Dosing simulations for amikacin supported the use of high dosing regimens (>= 25 mg/kg) and extended intervals (36 to 48 h) for most patients when considering PK/pharmacodynamic (PD) targets of a maximum concentration in plasma (C-max)/MIC ratio of >= 8 and a minimal concentration o

A validated method for the quantification of fosfomycin on dried plasma spots by HPLC-MS/MS: application to a pilot pharmacokinetic study in humans

Quantification of fosfomycin in the plasma samples of patients is the basis of clinical pharmacokinetic studies from which evidence based dosing regimens can be devised to maximise antibiotic effectiveness against a pathogen. We have developed and validated a LC–MS/MS method to quantify fosfomycin using dried plasma spot sampling. Following HILIC chromatography, fosfomycin and ethylphosphonic acid, used as internal standard, were measured using negative-ion multiple reaction monitoring. The method was linear over the calibration range of 5–2000 mg/L of fosfomycin. Intra-day assay results for dried plasma spot quality control samples at 15.6, 79.9 and 1581 mg/L of fosfomycin had precision of ±4.2, 8.2, and 2.0%, respectively, and accuracy of +3.9, −0.1, and −1.2%, respectively. Recovery of fosfomycin from dried plasma spots was calculated as 83.6% and the dried plasma spot samples were found to be stable stored at room temperature for three months and when stored for four hours at 50 °C. A Bland–Altman plot comparing DPS to plasma sampling found a negative bias of 16.6%, with all but one sample within the mean limits of agreement (−2.6 to 30.6%). Dried plasma spot sampling provides a useful tool for pharmacokinetic research of fosfomycin

The Theory of Fuzzy Logic and its application to Real Estate Valuation

Fuzzy logic is based on the central idea that in fuzzy sets each element in the set can assume a value from 0 to 1, not just 0 or 1, as in classic set theory. Thus, qualitative characteristics and numerically scaled measures can exhibit gradations in the extent to which they belong to the relevant sets for evaluation. This degree of membership of each element is a measure of the element’s "belonging" to the set, and thus of the precision with which it explains the phenomenon being evaluated. Fuzzy sets can be combined to produce meaningful conclusions, and inferences can be made, given a specified fuzzy input function. The article demonstrates the application of fuzzy logic to an income-producing property, with a resulting fuzzy set output

Effect of obesity on the population pharmacokinetics of meropenem in critically ill patients

Severe pathophysiological changes in critical illness can lead to dramatically altered antimicrobial pharmacokinetics (PK). The additional effect of obesity on PK potentially increases the challenge for effective dosing. The aim of this prospective study was to describe the population PK of meropenem for a cohort of critically ill patients, including obese and morbidly obese patients. Critically ill patients prescribed meropenem were recruited into the following three body mass index (BMI) groups: nonobese (18.5 to 29.9 kg/m(2)), obese (30.0 to 39.9 kg/m(2)), and morbidly obese (>= 40 kg/m(2)). Serial plasma samples were taken, and meropenem concentrations were determined using a validated chromatographic method. Population PK analysis and Monte Carlo dosing simulations were undertaken with Pmetrics. Nineteen critically ill patients with different BMI categories were enrolled. The patients' mean +/- standard deviation (SD) age, weight, and BMI were 49 +/- 15.9 years, 95 +/- 22.0 kg, and 33 +/- 7.0 kg/m(2), respectively. A two-compartment model described the data adequately. The mean +/- SD parameter estimates for the final covariate model were as follows: clearance (CL), 15.5 +/- 6.0 liters/h; volume of distribution in the central compartment (V-1), 11.7 +/- 5.8 liters; intercompartmental clearance from the central compartment to the peripheral compartment, 25.6 +/- 35.1 liters h(-1); and intercompartmental clearance from the peripheral compartment to the central compartment, 8.32 +/- 12.24 liters h(-1). Higher creatinine clearance (CLCR) was associated with a lower probability of target attainment, with BMI having little effect. Although obesity was found to be associated with an increased V-1, dose adjustment based on CLCR appears to be more important than patient BMI

Tumor-associated endothelial cells display GSTP1 and RARβ2 promoter methylation in human prostate cancer

BACKGROUND: A functional blood supply is essential for tumor growth and proliferation. However, the mechanism of blood vessel recruitment to the tumor is still poorly understood. Ideally, a thorough molecular assessment of blood vessel cells would be critical in our comprehension of this process. Yet, to date, there is little known about the molecular makeup of the endothelial cells of tumor-associated blood vessels, due in part to the difficulty of isolating a pure population of endothelial cells from the heterogeneous tissue environment. METHODS: Here we describe the use of a recently developed technique, Expression Microdissection, to isolate endothelial cells from the tumor microenvironment. The methylation status of the dissected samples was evaluated for GSTP1 and RARβ2 promoters via the QMS-PCR method. RESULTS: Comparing GSTP1 and RARβ2 promoter methylation data, we show that 100% and 88% methylation is detected, respectively, in the tumor areas, both in epithelium and endothelium. Little to no methylation is observed in non-tumor tissue areas. CONCLUSION: We applied an accurate microdissection technique to isolate endothelial cells from tissues, enabling DNA analysis such as promoter methylation status. The observations suggest that epigenetic alterations may play a role in determining the phenotype of tumor-associated vasculature

Beta-Lactam Infusion in Severe Sepsis (BLISS): a prospective, two-centre, open-labelled randomised controlled trial of continuous versus intermittent beta-lactam infusion in critically ill patients with severe sepsis

This study aims to determine if continuous infusion (CI) is associated with better clinical and pharmacokinetic/pharmacodynamic (PK/PD) outcomes compared to intermittent bolus (IB) dosing in critically ill patients with severe sepsis. This was a two-centre randomised controlled trial of CI versus IB dosing of beta-lactam antibiotics, which enrolled critically ill participants with severe sepsis who were not on renal replacement therapy (RRT). The primary outcome was clinical cure at 14 days after antibiotic cessation. Secondary outcomes were PK/PD target attainment, ICU-free days and ventilator-free days at day 28 post-randomisation, 14- and 30-day survival, and time to white cell count normalisation. A total of 140 participants were enrolled with 70 participants each allocated to CI and IB dosing. CI participants had higher clinical cure rates (56 versus 34 %, p = 0.011) and higher median ventilator-free days (22 versus 14 days, p MIC than the IB arm on day 1 (97 versus 70 %, p < 0.001) and day 3 (97 versus 68 %, p < 0.001) post-randomisation. There was no difference in 14-day or 30-day survival between the treatment arms. In critically ill patients with severe sepsis not receiving RRT, CI demonstrated higher clinical cure rates and had better PK/PD target attainment compared to IB dosing of beta-lactam antibiotics. Continuous beta-lactam infusion may be mostly advantageous for critically ill patients with high levels of illness severity and not receiving RRT

Pharmacokinetics of piperacillin in critically ill Australian Indigenous patients with severe sepsis

There are no available pharmacokinetic data to guide piperacillin dosing in critically ill Australian Indigenous patients despite numerous reported physiological differences. This study aimed to describe the population pharmacokinetics of piperacillin in critically ill Australian Indigenous patients with severe sepsis. A population pharmacokinetic study of Indigenous patients with severe sepsis was conducted in a remote hospital intensive care unit. Plasma samples were collected over two dosing intervals and assayed by validated chromatography. Population pharmacokinetic modeling was conducted using Pmetrics. Nine patients were recruited, and a two-compartment model adequately described the data. The piperacillin clearance (CL), volume of distribution of the central compartment (V-c), and distribution rate constants from the central to the peripheral compartment and from the peripheral to the central compartment were 5.6 +/- 3.2 liters/h, 14.5 +/- 6.6 liters, 1.5 +/- 0.4 h(-1), and 1.8 +/- 0.9 h(-1), respectively, where CL and Vc were found to be described by creatinine clearance (CLCR) and total body weight, respectively. In this patient population, piperacillin demonstrated high interindividual pharmacokinetic variability. CLCR was found to be the most important determinant of piperacillin pharmacokinetics

Optimising meropenem dosing in critically ill Australian Indigenous patients with severe sepsis

Currently there are no pharmacokinetic (PK) data to guide antibiotic dosing in critically ill Australian Indigenous patients with severe sepsis. This study aimed to determine whether the population pharmacokinetics of meropenem were different between critically ill Australian Indigenous and critically ill Caucasian patients. Serial plasma and urine samples as well as clinical and demographic data were collected over two dosing intervals from critically ill Australian Indigenous patients. Plasma meropenem concentrations were assayed by validated chromatography. Concentration-time data were analysed with data from a previous PK study in critically ill Caucasian patients using Pmetrics. The population PK model was subsequently used for Monte Carlo dosing simulations to describe optimal doses for these patients. Six Indigenous and five Caucasian subjects were included. A two-compartment model described the data adequately, with meropenem clearance and volume of distribution of the central compartment described by creatinine clearance (CLCr) and patient weight, respectively. Patient ethnicity was not supported as a covariate in the final model. Significant differences were observed for meropenem clearance between the Indigenous and Caucasian groups [ median 11.0 (range 3.0-14.1) L/h vs. 17.4 (4.3-30.3) L/h, respectively; P < 0.01]. Standard dosing regimens (1 g intravenous every 8 h as a 30-min infusion) consistently achieved target exposures at the minimum inhibitory concentration breakpoint in the absence of augmented renal clearance. No significant interethnic differences in meropenem pharmacokinetics between the Indigenous and Caucasian groups were detected and CLCr was found to be the strongest determinant of appropriate dosing regimens. Crown Copyright (C) 2016 Published by Elsevier B.V. All rights reserved