Wave intensity analysis: A novel non-invasive method for determining arterial wave transmission

Wave intensity analysis is a novel technique for assessing wavelet transmission in the cardiovascular system. Using this tool, we have developed non-invasive techniques to study wave transmission in both central & peripheral arteries in man. The aim of this study was to determine the reproducibility of various haemodynamic measures in the carotid, brachial and radial arteries. 12 treated hypertensive men underwent applanation tonometry and pulsed Doppler ultrasound studies of the carotid, brachial and radial arteries on 2 occasions. Coefficients of variation for the local wave speed, cardiac compression wave intensity and main reflected wave intensity ranged between 3.7-6.6%, 8.2-11.4% and 12.5-19.6% respectively. We conclude that non-invasive methods used for wave intensity analysis are reproducible & provide additional information regarding the complex phenomenon of arterial wave transmission in man

Incidence of pregnancy among women accessing antiretroviral therapy in urban Malawi: a retrospective cohort study.

Although previous studies investigated pregnancy rates among women on antiretroviral therapy (ART), incidence of, and factors associated with pregnancy among these women remain poorly understood. We, therefore, conducted a retrospective cohort study at a large public HIV clinic in Lilongwe, Malawi, between July 2007 and December 2010. At each clinic visit, pregnancy status was assessed. Time to event analysis was conducted using Poisson regression. Among 4,738 women, 589 pregnancies were observed. Pregnancy incidence was 9.3/100 person-years. After 6 months on ART, women on ART had similar total fertility rates to women in the urban population. In multivariable analysis, increasing age and advanced WHO clinical stage were associated with decreased probability of becoming pregnant while higher body mass index and longer time on ART were associated with increased probability of becoming pregnant. We recommend that ART clinics integrate comprehensive family planning services to address reproductive health needs among women on ART

Limitations of augmentation index in the assessment of wave reflection in normotensive healthy individuals

Objectives Augmentation index (AIx) is widely used as a measure of wave reflection. We compared the relationship between AIx and age, height and sex with ‘gold standard’ measures of wave reflection derived from measurements of pressure and flow to establish how well AIx measures wave reflection. Materials and Methods Measurements of carotid pressure and flow velocity were made in the carotid artery of 65 healthy normotensive individuals (age 21–78 yr; 43 male) and pulse wave analysis, wave intensity analysis and wave separation was performed; waveforms were classified into type A, B or C. AIx, the time of the first shoulder (Ts), wave reflection index (WRI) and the ratio of backward to forward pressure (Pb/Pf) were calculated. Results AIx did not correlate with log WRI or Pb/Pf. When AIx was restricted to positive values AIx and log WRI were positively correlated (r = 0.33; p = 0.04). In contrast log WRI and Pb/Pf were closely correlated (r = 0.66; p<0.001). There was no correlation between the Ts and the timing of Pb or the reflected wave identified by wave intensity analysis. Wave intensity analysis showed that the morphology of type C waveforms (negative AIx) was principally due to a forward travelling (re-reflected) decompression wave in mid-systole. AIx correlated positively with age, inversely with height and was higher in women. In contrast log WRI and Pb/Pf showed negative associations with age, were unrelated to height and did not differ significantly by gender. Conclusions AIx has serious limitations as a measure of wave reflection. Negative AIx values derived from Type C waves should not be used as estimates of wave reflection magnitude

Multiphysics Modelling and Simulation of Thrombolysis via Activated Platelet-Targeted Nanomedicine

PURPOSE: This study establishes a multiphysics simulation platform for both conventional and targeted thrombolysis using tissue plasminogen activator (tPA). Based on our computational results, the effects of therapeutic parameters on the dynamics of thrombolysis and the risk of side effects are investigated. METHODS: The model extends our previously developed one-dimensional(1D) mathematical models for fibrinolysis by incorporating targeted thrombolysis. It consists of two parts: (i) a coupled mathematical model of systemic pharmacokinetics (PK) and pharmacodynamics (PD) and local PD in a 1D occluded artery, and (ii) a mechanistic model for a targeted thrombolytic system via activated platelet-targeted tPA-loaded nanovesicles (tPA-NV), with model parameters derived from our in vitro experiments. A total of 16 therapeutic scenarios are simulated by varying the clot location and composition as well as the dosing regimen with free tPA or tPA-NV. RESULTS: Our simulation results indicate that tPA-NV offers several advantages over free tPA for thrombolysis. It reduces systemic exposure of tPA, thereby minimising the risk of bleeding complications. Simulations with different tPA-NV doses reveal that tPA-NV at 10% of the recommended dose can be as effective as the standard regimen with the full recommended dose of free tPA, demonstrating the potential of our tPA-NV as a new thrombolytic strategy with a reduced tPA dose. Moreover, faster recanalisation can be achieved with tPA-NV, especially for platelet-rich(or fibrin-poor) clots. CONCLUSIONS: Our simulation platform for thrombolysis with well-tuned model parameters can be used to evaluate and optimise treatment regimens of existing and new thrombolytic therapies via benefit/risk assessment under various therapeutic scenarios

Herps at height: Records of seven species utilizing the upper canopy in northwestern Ecuador

Canopy science has not developed as rapidly as other fields due to the inherent difficulty of accessing this ecosystem. Using a blend of industrial and arboricultural rope access techniques, we confirmed occurrences in the canopy of five reptile and two amphibian species in the Chocóan forests of northwestern Ecuador. RESUMEN La investigación en el dosel no se ha desarrollado con la misma velocidad que otras áreas debido a la inaccesibilidad de este ecosistema. Utilizando una combinación de técnicas de acceso con cuerdas de arboricultura e industria, confirmamos la ocurrencia del dosel de cinco especies de reptiles y dos especies de anfibios en los bosques del Chocó del noroccidente del Ecuador

Automatic optic disc detection in colour fundus images by means of multispectral analysis and information content

The optic disc (OD) in retinal fundus images is widely used as a reference in computer-based systems for the measurement of the severity of retinal disease. A number of algorithms have been published in the past 5 years to locate and measure the OD in digital fundus images. Our proposed algorithm, automatically: (i) uses the three channels (RGB) of the digital colour image to locate the region of interest (ROI) where the OD lies, (ii) measures the Shannon information content per channel in the ROI, to decide which channel is most appropriate for searching for the OD centre using the circular Hough transform. A series of evaluations were undertaken to test our hypothesis that using the three channels gives a better performance than a single channel. Three different databases were used for evaluation purposes with a total of 2,371 colour images giving a misdetection error of 3% in the localisation of the centre of the OD. We find that the area determined by our algorithm which assumes that the OD is circular, is similar to that found by other algorithms that detected the shape of the OD. Five metrics were measured for comparison with other recent studies. Combining the two databases where expert delineation of the OD is available (1,240 images), the average results for our multispectral algorithm are: TPR = 0.879, FPR = 0.003, Accuracy = 0.994, Overlap = 80.6% and Dice index = 0.878

Inflammatory Aetiology of Human Myometrial Activation Tested Using Directed Graphs

There are three main hypotheses for the activation of the human uterus at labour: functional progesterone withdrawal, inflammatory stimulation, and oxytocin receptor activation. To test these alternatives we have taken information and data from the literature to develop causal pathway models for the activation of human myometrium. The data provided quantitative RT-PCR results on key genes from samples taken before and during labour. Principal component analysis showed that pre-labour samples form a homogenous group compared to those during labour. We therefore modelled the alternative causal pathways in non-labouring samples using directed graphs and statistically compared the likelihood of the different models using structural equations and D-separation approaches. Using the computer program LISREL, inflammatory activation as a primary event was highly consistent with the data (p = 0.925), progesterone withdrawal, as a primary event, is plausible (p = 0.499), yet comparatively unlikely, oxytocin receptor mediated initiation is less compatible with the data (p = 0.091). DGraph, a software program that creates directed graphs, produced similar results (p = 0.684, p = 0.280, and p = 0.04, respectively). This outcome supports an inflammatory aetiology for human labour. Our results demonstrate the value of directed graphs in determining the likelihood of causal relationships in biology in situations where experiments are not possible

International Veterinary Epilepsy Task Force recommendations for systematic sampling and processing of brains from epileptic dogs and cats

Traditionally, histological investigations of the epileptic brain are required to identify epileptogenic brain lesions, to evaluate the impact of seizure activity, to search for mechanisms of drug-resistance and to look for comorbidities. For many instances, however, neuropathological studies fail to add substantial data on patients with complete clinical work-up. This may be due to sparse training in epilepsy pathology and or due to lack of neuropathological guidelines for companion animals. The protocols introduced herein shall facilitate systematic sampling and processing of epileptic brains and therefore increase the efficacy, reliability and reproducibility of morphological studies in animals suffering from seizures. Brain dissection protocols of two neuropathological centres with research focus in epilepsy have been optimised with regards to their diagnostic yield and accuracy, their practicability and their feasibility concerning clinical research requirements. The recommended guidelines allow for easy, standardised and ubiquitous collection of brain regions, relevant for seizure generation. Tissues harvested the prescribed way will increase the diagnostic efficacy and provide reliable material for scientific investigations

Excess Pressure Integral Predicts Cardiovascular Events Independent of Other Risk Factors in the Conduit Artery Functional Evaluation Substudy of Anglo-Scandinavian Cardiac Outcomes Trial

Excess pressure integral (XSPI), a new index of surplus work performed by the left ventricle, can be calculated from blood pressure waveforms and may indicate circulatory dysfunction. We investigated whether XSPI predicted future cardiovascular events and target organ damage in treated hypertensive individuals. Radial blood pressure waveforms were acquired by tonometry in 2069 individuals (aged, 63±8 years) in the Conduit Artery Functional Evaluation (CAFE) substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Measurements of left ventricular mass index (n=862) and common carotid artery intima media thickness (n=923) were also performed. XSPI and the integral of reservoir pressure were lower in people treated with amlodipine±perindopril than in those treated with atenolol±bendroflumethiazide, although brachial systolic blood pressure was similar. A total of 134 cardiovascular events accrued during a median 3.4 years of follow-up; XSPI was a significant predictor of cardiovascular events after adjustment for age and sex, and this relationship was unaffected by adjustment for conventional cardiovascular risk factors or Framingham risk score. XSPI, central systolic blood pressure, central augmentation pressure, central pulse pressure, and integral of reservoir pressure were correlated with left ventricular mass index, but only XSPI, augmentation pressure, and central pulse pressure were associated positively with carotid artery intima media thickness. Associations between left ventricular mass index, XSPI, and integral of reservoir pressure and carotid artery intima media thickness and XSPI were unaffected by multivariable adjustment for other covariates. XSPI is a novel indicator of cardiovascular dysfunction and independently predicts cardiovascular events and targets organ damage in a prospective clinical trial