Statnote 22: Measuring 'agreement'

If a quantity has been measured by two different methods, the degree of agreement between them should not be tested using Pearson’s correlation coefficient ‘r’. Instead the differences between the two methods should be compared with their mean difference using a Bland and Altman plot. Such a plot illustrates the level of agreement between two methods and enables the degree of bias of one method over the other to be calculated and applied if necessary as a correction factor.

Corneal pachymetry in normal and keratoconic eyes:Orbscan II versus ultrasound

Purpose: To compare corneal thickness measurements using Orbscan II (OII) and ultrasonic (US) pachymetry in normal and in keratoconic eyes. Setting: Eye Department, Heartlands and Solihull NHS Trust, Birmingham, United Kingdom. Methods: Central corneal thickness (CCT) was measured by means of OII and US pachymetry in 1 eye of 72 normal subjects and 36 keratoconus patients. The apical corneal thickness (ACT) in keratoconus patients was also evaluated using each method. The mean of the difference, standard deviation (SD), and 95% limits of agreement (LoA = mean ± 2 SD), with and without applying the default linear correction factor (LCF), were determined for each sample. The Student t test was used to identify significant differences between methods, and the correlation between methods was determined using the Pearson bivariate correlation. Bland-Altman analysis was performed to confirm that the results of the 2 instruments were clinically comparable. Results: In normal eyes, the mean difference (± 95% LoA) in CCT was 1.04 μm ± 68.52 (SD) (P>.05; r = 0.71) when the LCF was used and 46.73 ± 75.40 μm (P = .0001; r = 0.71) without the LCF. In keratoconus patients, the mean difference (± 95% LoA) in CCT between methods was 42.46 ± 66.56 μm (P<.0001: r = 0.85) with the LCF, and 2.51 ± 73.00 μm (P>.05: r = 0.85) without the LCF. The mean difference (± 95% LoA) in ACT for this group was 49.24 ± 60.88 μm (P<.0001: r = 0.89) with the LCF and 12.71 ± 68.14 μm (P = .0077; r = 0.89) when the LCF was not used. Conclusions: This study suggests that OII and US pachymetry provide similar readings for CCT in normal subjects when an LCF is used. In keratoconus patients, OII provides a valid clinical tool for the noninvasive assessment of CCT when the LCF is not applied. © 2004 ASCRS and ESCRS.

Carbon monoxide inhibits sprouting angiogenesis and vascular endothelial growth factor receptor-2 phosphorylation

Carbon monoxide (CO) is a gaseous autacoid known to positively regulate vascular tone; however, its role in angiogenesis is unknown. The aim of this study was to investigate the effect of CO on angiogenesis and vascular endothelial growth factor (VEGF) receptor-2 phosphorylation. Human umbilical vein endothelial cells (HUVECs) were cultured on growth factor- reduced Matrigel and treated with a CO-releasing molecule (CORM-2) or exposed to CO gas (250 ppm). Here, we report the surprising finding that exposure to CO inhibits vascular endothelial growth factor (VEGF)-induced endothelial cell actin reorganisation, cell proliferation, migration and capillary-like tube formation. Similarly, CO suppressed VEGF-mediated phosphorylation of VEGFR-2 at tyrosine residue 1175 and 1214 and basic fibroblast growth factor- (FGF-2) and VEGF-mediated Akt phosphorylation. Consistent with these data, mice exposed to 250 ppm CO (1h/day for 14 days) exhibited a marked decrease in FGF-2-induced Matrigel plug angiogenesis (p<0.05). These data establish a new biological function for CO in angiogenesis and point to a potential therapeutic use for CO as an anti-angiogenic agent in tumour suppression.

Model thrombi formed under flow reveal the role of factor XIII-mediated cross-linking in resistance to fibrinolysis

Background: Activated factor XIII (FXIIIa), a transglutaminase, introduces fibrin-fibrin and fibrin-inhibitor cross-links, resulting in more mechanically stable clots. The impact of cross-linking on resistance to fibrinolysis has proved challenging to evaluate quantitatively. Methods: We used a whole blood model thrombus system to characterize the role of cross-linking in resistance to fibrinolytic degradation. Model thrombi, which mimic arterial thrombi formed in vivo, were prepared with incorporated fluorescently labeled fibrinogen, in order to allow quantification of fibrinolysis as released fluorescence units per minute. Results: A site-specific inhibitor of transglutaminases, added to blood from normal donors, yielded model thrombi that lysed more easily, either spontaneously or by plasminogen activators. This was observed both in the cell/platelet-rich head and fibrin-rich tail. Model thrombi from an FXIII-deficient patient lysed more quickly than normal thrombi; replacement therapy with FXIII concentrate normalized lysis. In vitro addition of purified FXIII to the patient's preprophylaxis blood, but not to normal control blood, resulted in more stable thrombi, indicating no further efficacy of supraphysiologic FXIII. However, addition of tissue transglutaminase, which is synthesized by endothelial cells, generated thrombi that were more resistant to fibrinolysis; this may stabilize mural thrombi in vivo. Conclusions: Model thrombi formed under flow, even those prepared as plasma 'thrombi', reveal the effect of FXIII on fibrinolysis. Although very low levels of FXIII are known to produce mechanical clot stability, and to achieve ?-dimerization, they appear to be suboptimal in conferring full resistance to fibrinolysis.

Uses of frontier efficiency methodologies and multi-criteria decision making for performance measurement in the energy sector

Guest editorial Ali Emrouznejad is a Senior Lecturer at the Aston Business School in Birmingham, UK. His areas of research interest include performance measurement and management, efficiency and productivity analysis as well as data mining. He has published widely in various international journals. He is an Associate Editor of IMA Journal of Management Mathematics and Guest Editor to several special issues of journals including Journal of Operational Research Society, Annals of Operations Research, Journal of Medical Systems, and International Journal of Energy Management Sector. He is in the editorial board of several international journals and co-founder of Performance Improvement Management Software. William Ho is a Senior Lecturer at the Aston University Business School. Before joining Aston in 2005, he had worked as a Research Associate in the Department of Industrial and Systems Engineering at the Hong Kong Polytechnic University. His research interests include supply chain management, production and operations management, and operations research. He has published extensively in various international journals like Computers & Operations Research, Engineering Applications of Artificial Intelligence, European Journal of Operational Research, Expert Systems with Applications, International Journal of Production Economics, International Journal of Production Research, Supply Chain Management: An International Journal, and so on. His first authored book was published in 2006. He is an Editorial Board member of the International Journal of Advanced Manufacturing Technology and an Associate Editor of the OR Insight Journal. Currently, he is a Scholar of the Advanced Institute of Management Research. Uses of frontier efficiency methodologies and multi-criteria decision making for performance measurement in the energy sector This special issue aims to focus on holistic, applied research on performance measurement in energy sector management and for publication of relevant applied research to bridge the gap between industry and academia. After a rigorous refereeing process, seven papers were included in this special issue. The volume opens with five data envelopment analysis (DEA)-based papers. Wu et al. apply the DEA-based Malmquist index to evaluate the changes in relative efficiency and the total factor productivity of coal-fired electricity generation of 30 Chinese administrative regions from 1999 to 2007. Factors considered in the model include fuel consumption, labor, capital, sulphur dioxide emissions, and electricity generated. The authors reveal that the east provinces were relatively and technically more efficient, whereas the west provinces had the highest growth rate in the period studied. Ioannis E. Tsolas applies the DEA approach to assess the performance of Greek fossil fuel-fired power stations taking undesirable outputs into consideration, such as carbon dioxide and sulphur dioxide emissions. In addition, the bootstrapping approach is deployed to address the uncertainty surrounding DEA point estimates, and provide bias-corrected estimations and confidence intervals for the point estimates. The author revealed from the sample that the non-lignite-fired stations are on an average more efficient than the lignite-fired stations. Maethee Mekaroonreung and Andrew L. Johnson compare the relative performance of three DEA-based measures, which estimate production frontiers and evaluate the relative efficiency of 113 US petroleum refineries while considering undesirable outputs. Three inputs (capital, energy consumption, and crude oil consumption), two desirable outputs (gasoline and distillate generation), and an undesirable output (toxic release) are considered in the DEA models. The authors discover that refineries in the Rocky Mountain region performed the best, and about 60 percent of oil refineries in the sample could improve their efficiencies further. H. Omrani, A. Azadeh, S. F. Ghaderi, and S. Abdollahzadeh presented an integrated approach, combining DEA, corrected ordinary least squares (COLS), and principal component analysis (PCA) methods, to calculate the relative efficiency scores of 26 Iranian electricity distribution units from 2003 to 2006. Specifically, both DEA and COLS are used to check three internal consistency conditions, whereas PCA is used to verify and validate the final ranking results of either DEA (consistency) or DEA-COLS (non-consistency). Three inputs (network length, transformer capacity, and number of employees) and two outputs (number of customers and total electricity sales) are considered in the model. Virendra Ajodhia applied three DEA-based models to evaluate the relative performance of 20 electricity distribution firms from the UK and the Netherlands. The first model is a traditional DEA model for analyzing cost-only efficiency. The second model includes (inverse) quality by modelling total customer minutes lost as an input data. The third model is based on the idea of using total social costs, including the firm’s private costs and the interruption costs incurred by consumers, as an input. Both energy-delivered and number of consumers are treated as the outputs in the models. After five DEA papers, Stelios Grafakos, Alexandros Flamos, Vlasis Oikonomou, and D. Zevgolis presented a multiple criteria analysis weighting approach to evaluate the energy and climate policy. The proposed approach is akin to the analytic hierarchy process, which consists of pairwise comparisons, consistency verification, and criteria prioritization. In the approach, stakeholders and experts in the energy policy field are incorporated in the evaluation process by providing an interactive mean with verbal, numerical, and visual representation of their preferences. A total of 14 evaluation criteria were considered and classified into four objectives, such as climate change mitigation, energy effectiveness, socioeconomic, and competitiveness and technology. Finally, Borge Hess applied the stochastic frontier analysis approach to analyze the impact of various business strategies, including acquisition, holding structures, and joint ventures, on a firm’s efficiency within a sample of 47 natural gas transmission pipelines in the USA from 1996 to 2005. The author finds that there were no significant changes in the firm’s efficiency by an acquisition, and there is a weak evidence for efficiency improvements caused by the new shareholder. Besides, the author discovers that parent companies appear not to influence a subsidiary’s efficiency positively. In addition, the analysis shows a negative impact of a joint venture on technical efficiency of the pipeline company. To conclude, we are grateful to all the authors for their contribution, and all the reviewers for their constructive comments, which made this special issue possible. We hope that this issue would contribute significantly to performance improvement of the energy sector.

Activation of proteinase-activated receptor 2 stimulates soluble vascular endothelial growth factor receptor 1 release via epidermal growth factor receptor transactivation in endothelial cells

The proteinase-activated receptor 2 (PAR-2) expression is increased in endothelial cells derived from women with preeclampsia, characterized by widespread maternal endothelial damage, which occurs as a consequence of elevated soluble vascular endothelial growth factor receptor-1 (sVEGFR-1; commonly known as sFlt-1) in the maternal circulation. Because PAR-2 is upregulated by proinflammatory cytokines and activated by blood coagulation serine proteinases, we investigated whether activation of PAR-2 contributed to sVEGFR-1 release. PAR-2–activating peptides (SLIGRL-NH2 and 2-furoyl-LIGRLO-NH2) and factor Xa increased the expression and release of sVEGFR-1 from human umbilical vein endothelial cells. Enzyme-specific, dominant-negative mutants and small interfering RNA were used to demonstrate that PAR-2–mediated sVEGFR-1 release depended on protein kinase C-ß1 and protein kinase C-e, which required intracellular transactivation of epidermal growth factor receptor 1, leading to mitogen-activated protein kinase activation. Overexpression of heme oxygenase 1 and its gaseous product, carbon monoxide, decreased PAR-2–stimulated sVEGFR-1 release from human umbilical vein endothelial cells. Simvastatin, which upregulates heme oxygenase 1, also suppressed PAR-2–mediated sVEGFR-1 release. These results show that endothelial PAR-2 activation leading to increased sVEGFR-1 release may contribute to the maternal vascular dysfunction observed in preeclampsia and highlights the PAR-2 pathway as a potential therapeutic target for the treatment of preeclampsia.

A sensing mechanism for the detection of carbon nanotubes using selective photoluminescent probes based on ionic complexes with organic dyes

The multifunctional properties of carbon nanotubes (CNTs) make them a powerful platform for unprecedented innovations in a variety of practical applications. As a result of the surging growth of nanotechnology, nanotubes present a potential problem as an environmental pollutant, and as such, an efficient method for their rapid detection must be established. Here, we propose a novel type of ionic sensor complex for detecting CNTs – an organic dye that responds sensitively and selectively to CNTs with a photoluminescent signal. The complexes are formed through Coulomb attractions between dye molecules with uncompensated charges and CNTs covered with an ionic surfactant in water. We demonstrate that the photoluminescent excitation of the dye can be transferred to the nanotubes, resulting in selective and strong amplification (up to a factor of 6) of the light emission from the excitonic levels of CNTs in the near-infrared spectral range, as experimentally observed via excitation-emission photoluminescence (PL) mapping. The chirality of the nanotubes and the type of ionic surfactant used to disperse the nanotubes both strongly affect the amplification; thus, the complexation provides sensing selectivity towards specific CNTs. Additionally, neither similar uncharged dyes nor CNTs covered with neutral surfactant form such complexes. As model organic molecules, we use a family of polymethine dyes with an easily tailorable molecular structure and, consequently, tunable absorbance and PL characteristics. This provides us with a versatile tool for the controllable photonic and electronic engineering of an efficient probe for CNT detection.