Accuracy of popular automatic QT Interval algorithms assessed by a 'Gold Standard' and comparison with a Novel method: computer simulation study

BACKGROUND: Accurate measurement of the QT interval is very important from a clinical and pharmaceutical drug safety screening perspective. Expert manual measurement is both imprecise and imperfectly reproducible, yet it is used as the reference standard to assess the accuracy of current automatic computer algorithms, which thus produce reproducible but incorrect measurements of the QT interval. There is a scientific imperative to evaluate the most commonly used algorithms with an accurate and objective 'gold standard' and investigate novel automatic algorithms if the commonly used algorithms are found to be deficient. METHODS: This study uses a validated computer simulation of 8 different noise contaminated ECG waveforms (with known QT intervals of 461 and 495 ms), generated from a cell array using Luo-Rudy membrane kinetics and the Crank-Nicholson method, as a reference standard to assess the accuracy of commonly used QT measurement algorithms. Each ECG contaminated with 39 mixtures of noise at 3 levels of intensity was first filtered then subjected to three threshold methods (T1, T2, T3), two T wave slope methods (S1, S2) and a Novel method. The reproducibility and accuracy of each algorithm was compared for each ECG. RESULTS: The coefficient of variation for methods T1, T2, T3, S1, S2 and Novel were 0.36, 0.23, 1.9, 0.93, 0.92 and 0.62 respectively. For ECGs of real QT interval 461 ms the methods T1, T2, T3, S1, S2 and Novel calculated the mean QT intervals(standard deviations) to be 379.4(1.29), 368.5(0.8), 401.3(8.4), 358.9(4.8), 381.5(4.6) and 464(4.9) ms respectively. For ECGs of real QT interval 495 ms the methods T1, T2, T3, S1, S2 and Novel calculated the mean QT intervals(standard deviations) to be 396.9(1.7), 387.2(0.97), 424.9(8.7), 386.7(2.2), 396.8(2.8) and 493(0.97) ms respectively. These results showed significant differences between means at >95% confidence level. Shifting ECG baselines caused large errors of QT interval with T1 and T2 but no error with Novel. CONCLUSION: The algorithms T2, T1 and Novel gave low coefficients of variation for QT measurement. The Novel technique gave the most accurate measurement of QT interval, T3 (a differential threshold method) was the next most accurate by a large margin. The objective and accurate 'gold standard' presented in this paper may be useful to assess new QT measurement algorithms. The Novel algorithm may prove to be more accurate and reliable method to measure the QT interval

A broad distribution of the alternative oxidase in microsporidian parasites

Microsporidia are a group of obligate intracellular parasitic eukaryotes that were considered to be amitochondriate until the recent discovery of highly reduced mitochondrial organelles called mitosomes. Analysis of the complete genome of Encephalitozoon cuniculi revealed a highly reduced set of proteins in the organelle, mostly related to the assembly of ironsulphur clusters. Oxidative phosphorylation and the Krebs cycle proteins were absent, in keeping with the notion that the microsporidia and their mitosomes are anaerobic, as is the case for other mitosome bearing eukaryotes, such as Giardia. Here we provide evidence opening the possibility that mitosomes in a number of microsporidian lineages are not completely anaerobic. Specifically, we have identified and characterized a gene encoding the alternative oxidase (AOX), a typically mitochondrial terminal oxidase in eukaryotes, in the genomes of several distantly related microsporidian species, even though this gene is absent from the complete genome of E. cuniculi. In order to confirm that these genes encode functional proteins, AOX genes from both A. locustae and T. hominis were over-expressed in E. coli and AOX activity measured spectrophotometrically using ubiquinol-1 (UQ-1) as substrate. Both A. locustae and T. hominis AOX proteins reduced UQ-1 in a cyanide and antimycin-resistant manner that was sensitive to ascofuranone, a potent inhibitor of the trypanosomal AOX. The physiological role of AOX microsporidia may be to reoxidise reducing equivalents produced by glycolysis, in a manner comparable to that observed in trypanosome

Latent class analysis of sexual health markers among men and women participating in a British probability sample survey.

BACKGROUND: Despite known associations between different aspects of sexual health, it is not clear how patterning of adverse sexual health varies across the general population. A better understanding should contribute towards more effective problem identification, prevention and treatment. We sought to identify different clusters of sexual health markers in a general population, along with their socio-demographic, health and lifestyle correlates. METHODS: Data came from men (N = 5113) and women (N = 7019) aged 16-74 who reported partnered sexual activity in the past year in Britain's third National Survey of Sexual Attitudes and Lifestyles, undertaken in 2010-2012. Latent class analysis used 18 self-reported variables relating to adverse sexual health outcomes (STI and unplanned pregnancy, non-volitional sex, and sexual function problems). Correlates included socio-demographics, early debut, alcohol/drug use, depression, and satisfaction/distress with sex life. RESULTS: Four classes were found for men (labelled Good Sexual Health 83%, Wary Risk-takers 4%, Unwary Risk-takers 4%, Sexual Function Problems 9%); six for women (Good Sexual Health 52%, Wary Risk-takers 2%, Unwary Risk-takers 7%, Low Interest 29%, Sexual Function Problems 7%, Highly Vulnerable 2%). Regardless of gender, Unwary Risk-takers reported lower STI/HIV risk perception and more condomless sex than Wary Risk-takers, but both were more likely to report STI diagnosis than Good Sexual Health classes. Highly Vulnerable women reported abortion, STIs and functional problems, and more sexual coercion than other women. Distinct socio-demographic profiles differentiated higher-risk classes from Good Sexual Health classes, with depression, alcohol/drug use, and early sexual debut widely-shared correlates of higher-risk classes. Females in higher-risk classes, and men with functional problems, evaluated their sex lives more negatively than those with Good Sexual Health. CONCLUSIONS: A greater prevalence and diversity of poor sexual health appears to exist among women than men in Britain, with more consistent effects on women's subjective sexual well-being. Shared health and lifestyle characteristics of higher-risk groups suggest widespread benefits of upstream interventions. Several groups could benefit from tailored interventions: men and women who underestimate their STI/HIV risk exposure, women distressed by low interest in sex, and women experiencing multiple adverse outcomes. Distinctive socio-demographic profiles should assist with identification and targeting

Blood vessels as targets in tumor therapy

The landmark papers published by Judah Folkman in the early 1970s on tumor angiogenesis and therapeutic implications promoted the rapid development of a very dynamic field where basic scientists, oncologists, and pharmaceutical industry joined forces to determine the molecular mechanisms in blood vessel formation and find means to exploit this knowledge in suppressing tumor vascularization and growth. A wealth of information has been collected on angiogenic growth factors, and in 2004 the first specific blood vessel-targeted cancer therapy was introduced: a neutralizing antibody against vascular endothelial growth factor (VEGF). Now (2011) we know that suppression of tumor angiogenesis may be a double-edged sword and that the therapy needs to be further refined and individualized. This review describes the hallmarks of tumor vessels, how different angiogenic growth factors exert their function, and the perspectives for future development of anti-angiogenic therapy