Evaluation of a portable retinal imaging device: towards a comparative quantitative analysis for morphological measurements of retinal blood vessels

This study investigated the possibility of using low-cost, handheld, retinal imaging devices for the automatic extraction of quantifiable measures of retinal blood vessels. Initially, the available handheld devices were compared using a Zeiss model eye incorporating a USAF resolution test chart to assess their optical properties. The only suitable camera of the five evaluated was the Horus DEC 200. This device was then subjected to a detailed evaluation in which images in human eyes taken from the handheld camera were compared in a quantitative analysis with those of the same eye from a Canon CR-DGi retinal desktop camera. We found that the Horus DEC 200 exhibited shortcomings in capturing images of human eyes by comparison with the Canon. More images were rejected as being unevaluable or suffering failures in automatic segmentation than with the Canon, and even after exclusion of affected images, the Horus yielded lower measurements of vessel density than the Canon. A number of issues affecting handheld cameras in general and some features of the Horus in particular have been identified that might contribute to the observed differences in performance. Some potential mitigations are discussed which might yield improvements in performance, thus potentially facilitating use of handheld retinal imaging devices for quantitative retinal microvascular measurements

Fluid structure interaction of patient specific abdominal aortic aneurysms: a comparison with solid stress models

BACKGROUND: Abdominal aortic aneurysm (AAA) is a dilatation of the aortic wall, which can rupture, if left untreated. Previous work has shown that, maximum diameter is not a reliable determinant of AAA rupture. However, it is currently the most widely accepted indicator. Wall stress may be a better indicator and promising patient specific results from structural models using static pressure, have been published. Since flow and pressure inside AAA are non-uniform, the dynamic interaction between the pulsatile flow and wall may influence the predicted wall stress. The purpose of the present study was to compare static and dynamic wall stress analysis of patient specific AAAs. METHOD: Patient-specific AAA models were created from CT scans of three patients. Two simulations were performed on each lumen model, fluid structure interaction (FSI) model and static structural (SS) model. The AAA wall was created by dilating the lumen with a uniform 1.5 mm thickness, and was modeled as a non-linear hyperelastic material. Commercial finite element code Adina 8.2 was used for all simulations. The results were compared between the FSI and SS simulations. RESULTS: Results are presented for the wall stress patterns, wall shear stress patterns, pressure, and velocity fields within the lumen. It is demonstrated that including fluid flow can change local wall stresses slightly. However, as far as the peak wall stress is concerned, this effect is negligible as the difference between SS and FSI models is less than 1%. CONCLUSION: The results suggest that fully coupled FSI simulation, which requires considerable computational power to run, adds little to rupture risk prediction. This justifies the use of SS models in previous studies

Effect of Monthly, High‐Dose, Long‐Term Vitamin D Supplementation on Central Blood Pressure Parameters: A Randomized Controlled Trial Substudy

Background: The effects of monthly, high‐dose, long‐term (≥1‐year) vitamin D supplementation on central blood pressure (BP) parameters are unknown. Methods and Results: A total of 517 adults (58% male, aged 50–84 years) were recruited into a double‐blinded, placebo‐controlled trial substudy and randomized to receive, for 1.1 years (median; range: 0.9–1.5 years), either (1) vitamin D3 200 000 IU (initial dose) followed 1 month later by monthly 100 000‐IU doses (n=256) or (2) placebo monthly (n=261). At baseline (n=517) and follow‐up (n=380), suprasystolic oscillometry was undertaken, yielding aortic BP waveforms and hemodynamic parameters. Mean deseasonalized 25‐hydroxyvitamin D increased from 66 nmol/L (SD: 24) at baseline to 122 nmol/L (SD: 42) at follow‐up in the vitamin D group, with no change in the placebo group. Despite small, nonsignificant changes in hemodynamic parameters in the total sample (primary outcome), we observed consistently favorable changes among the 150 participants with vitamin D deficiency (<50 nmol/L) at baseline. In this subgroup, mean changes in the vitamin D group (n=71) versus placebo group (n=79) were −5.3 mm Hg (95% confidence interval [CI], −11.8 to 1.3) for brachial systolic BP (P=0.11), −2.8 mm Hg (95% CI, −6.2 to 0.7) for brachial diastolic BP (P=0.12), −7.5 mm Hg (95% CI, −14.4 to −0.6) for aortic systolic BP (P=0.03), −5.7 mm Hg (95% CI, −10.8 to −0.6) for augmentation index (P=0.03), −0.3 m/s (95% CI, −0.6 to −0.1) for pulse wave velocity (P=0.02), −8.6 mm Hg (95% CI, −15.4 to −1.9) for peak reservoir pressure (P=0.01), and −3.6 mm Hg (95% CI, −6.3 to −0.8) for backward pressure amplitude (P=0.01). Conclusions: Monthly, high‐dose, 1‐year vitamin D supplementation lowered central BP parameters among adults with vitamin D deficiency but not in the total sample. Clinical Trial Registration URL: http://www.anzctr.org.au. Unique identifier: ACTRN12611000402943

Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function

BACKGROUND: Understanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function. METHODS: A GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function. RESULTS: The discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication was performed in 5 cohorts (n = 14,321) and 6 cohorts (n = 16,308), respectively. Besides 5 previously reported loci, the combined meta-analysis identified 10 additional genome-wide significant SNPs: rs12541595 near MTSS1 and rs10774625 in ATXN2 for LV end-diastolic internal dimension; rs806322 near KCNRG, rs4765663 in CACNA1C, rs6702619 near PALMD, rs7127129 in TMEM16A, rs11207426 near FGGY, rs17608766 in GOSR2, and rs17696696 in CFDP1 for aortic root diameter; and rs12440869 in IQCH for Doppler transmitral A-wave peak velocity. Findings were in part validated in other cohorts and in GWAS of related disease traits. The genetic loci showed associations with putative signaling pathways, and with gene expression in whole blood, monocytes, and myocardial tissue. CONCLUSION: The additional genetic loci identified in this large meta-analysis of cardiac structure and function provide insights into the underlying genetic architecture of cardiac structure and warrant follow-up in future functional studies. FUNDING: For detailed information per study, see Acknowledgments.This work was supported by a grant from the US National Heart, Lung, and Blood Institute (N01-HL-25195; R01HL 093328 to RSV), a MAIFOR grant from the University Medical Center Mainz, Germany (to PSW), the Center for Translational Vascular Biology (CTVB) of the Johannes Gutenberg-University of Mainz, and the Federal Ministry of Research and Education, Germany (BMBF 01EO1003 to PSW). This work was also supported by the research project Greifswald Approach to Individualized Medicine (GANI_MED). GANI_MED was funded by the Federal Ministry of Education and Research and the Ministry of Cultural Affairs of the Federal State of Mecklenburg, West Pomerania (contract 03IS2061A). We thank all study participants, and the colleagues and coworkers from all cohorts and sites who were involved in the generation of data or in the analysis. We especially thank Andrew Johnson (FHS) for generation of the gene annotation database used for analysis. We thank the German Center for Cardiovascular Research (DZHK e.V.) for supporting the analysis and publication of this project. RSV is a member of the Scientific Advisory Board of the DZHK. Data on CAD and MI were contributed by CARDIoGRAMplusC4D investigators. See Supplemental Acknowledgments for consortium details. PSW, JFF, AS, AT, TZ, RSV, and MD had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis

Ethnic differences in carotid and left ventricular hypertrophy

a Objectives Afro-Caribbean subjects have a higher prevalence of hypertension, a lower prevalence of ischaemic heart disease and a higher premature mortality compared to White Europeans. Left ventricular hypertrophy (LVH) is also more prevalent in Afro-Caribbeans even at similar levels of blood pressure. It is widely believed that carotid artery intima±media thickening (IMT) represents an early marker for the development of atheroma, and carotid IMT and LVH are associated in White populations. Whether the relationship between carotid IMT and LVH is similar in Black subjects is unknown. Methods Thirty-eight subjects were studied using carotid and femoral ultrasonography and echocardiography; 19 Afro-Caribbean and 19 White European subjects were matched for age, sex and mean 24 h systolic blood pressure. Results The Afro-Caribbean group had a signi®cantly greater left ventricular mass index (LVMI) compared to the White European: 136.4 6 6.1 versus 112.4 6 6.2 g/m 2 , P , 0.01. However, carotid IMT, carotid diameter, femoral IMT and femoral diameter were similar between the groups: 0.75 6 0.02 versus 0.77 6 0.04 mm, 6.54 6 0.15 versus 6.56 6 0.16 mm, 0.66 6 0.03 versus 0.68 6 0.03 mm and 8.40 6 0.33 versus 8.25 6 0.23 mm, respectively. Conclusions Afro-Caribbean subjects with similar blood pressures have similar mean carotid and femoral IMTs compared to White Europeans, in spite of marked differences in LVMI. Whether this re¯ects a discrepancy in the degree of cardiovascular risk for similar levels of LVMI or whether this is a re¯ection of an altered pattern of target organ damage associated with hypertension in AfroCaribbean subjects is unclear

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

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.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 (T(s)), wave reflection index (WRI) and the ratio of backward to forward pressure (P(b)/P(f)) were calculated.AIx did not correlate with log WRI or P(b)/P(f). 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 P(b)/P(f) were closely correlated (r = 0.66; p<0.001). There was no correlation between the T(s) 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 P(b)/P(f) showed negative associations with age, were unrelated to height and did not differ significantly by gender.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

Mathematical Modelling of Intravenous Thrombolysis in Acute Ischaemic stroke: Effects of Dose Regimens on Levels of Fibrinolytic Proteins and Clot Lysis Time

Thrombolytic therapy is one of the medical procedures in the treatment of acute ischaemic stroke (AIS), whereby the tissue plasminogen activator (tPA) is intravenously administered to dissolve the obstructive blood clot. The treatment of AIS by thrombolysis can sometimes be ineffective and it can cause serious complications, such as intracranial haemorrhage (ICH). In this study, we propose an efficient mathematical modelling approach that can be used to evaluate the therapeutic efficacy and safety of thrombolysis in various clinically relevant scenarios. Our model combines the pharmacokinetics and pharmacodynamics of tPA with local clot lysis dynamics. By varying the drug dose, bolus-infusion delay time, and bolus-infusion ratio, with the FDA approved dosing protocol serving as a reference, we have used the model to simulate 13 dose regimens. Simulation results are compared for temporal concentrations of fibrinolytic proteins in plasma and the time that is taken to achieve recanalisation. Our results show that high infusion rates can cause the rapid degradation of plasma fibrinogen, indicative of increased risk for ICH, but they do not necessarily lead to fast recanalisation. In addition, a bolus-infusion delay results in an immediate drop in plasma tPA concentration, which prolongs the time to achieve recanalisation. Therefore, an optimal administration regimen should be sought by keeping the tPA level sufficiently high throughout the treatment and maximising the lysis rate while also limiting the degradation of fibrinogen in systemic plasma. This can be achieved through model-based optimisation in the future