Ultrasound entropy may be a new non-invasive measure of pre-clinical vascular damage in young hypertensive patients

Background: The identification of pre-clinical microvascular damage in hypertension by non-invasive techniques has proved frustrating for clinicians. This proof of concept study investigated whether entropy, a novel summary measure for characterizing blood velocity waveforms, is altered in participants with hypertension and may therefore be useful in risk stratification.

Methods: Doppler ultrasound waveforms were obtained from the carotid and retrobulbar circulation in 42 participants with uncomplicated grade 1 hypertension (mean systolic/diastolic blood pressure (BP) 142/92 mmHg), and 26 healthy controls (mean systolic/diastolic BP 116/69 mmHg). Mean wavelet entropy was derived from flow-velocity data and compared with traditional haemodynamic measures of microvascular function, namely the resistive and pulsatility indices.

Results: Entropy, was significantly higher in control participants in the central retinal artery (CRA) (differential mean 0.11 (standard error 0.05 cms(-1)), CI 0.009 to 0.219, p 0.017) and ophthalmic artery (0.12 (0.05), CI 0.004 to 0.215, p 0.04). In comparison, the resistive index (0.12 (0.05), CI 0.005 to 0.226, p 0.029) and pulsatility index (0.96 (0.38), CI 0.19 to 1.72, p 0.015) showed significant differences between groups in the CRA alone. Regression analysis indicated that entropy was significantly influenced by age and systolic blood pressure (r values 0.4-0.6). None of the measures were significantly altered in the larger conduit vessel.

Conclusion: This is the first application of entropy to human blood velocity waveform analysis and shows that this new technique has the ability to discriminate health from early hypertensive disease, thereby promoting the early identification of cardiovascular disease in a young hypertensive population.

Exceptionally Long Distance Transport of Volcanic Ash: Implications for Stratigraphy, Hazards and the Sourcing of Distal Tephra Deposits

Cryptotephras (tephra not visible to the naked eye) form the foundation of the tephrostratigraphic frameworks used in Europe to date and correlate widely distributed geologic, paleoenvironmental and archaeological records. Pyne-O'Donnell et al. (2012) established the potential for developing a similar crypto-tephrostratigraphy across eastern North America by identifying multiple tephra, including the White River Ash (east; WRAe), St. Helens We and East Lake, in a peat core located in Newfoundland. Following on from this work, several ongoing projects have examined additional peat cores from Michigan, New York State, Maine, Nova Scotia and Newfoundland to build a tephrostratigraphic framework for this region. Using the precedent set by recent research by Jensen et al.(in press) that correlated the Alaskan WRAe to the European cryptotephra AD860B, unknown tephras identified in this work were not necessarily assumed to be from "expected" source areas (e.g. the Cascades). Here we present several examples of the preservation of tephra layers with an intercontinental distribution (i.e. WRAe and Ksudach 1), from relatively small magnitude events (i.e. St. Helens layer T, Mono Crater), and the first example of a Mexican ash in the NE (Volcan Ceboruco, Jala pumice). There are several implications of the identification of these units. These far-travelled ashes: (1) highlight the need to consider "ultra" distal source volcanoes for unknown cryptotephra deposits,. (2) present an opportunity for physical volcanologists to examine why some eruptions have an exceptional distribution of ash that is not necessarily controlled by the magnitude of the event. (3) complicate the idea of using tephrostratigraphic frameworks to understand the frequency of eruptions towards aiding hazard planning and prediction (e.g. Swindles et al., 2011). (4) show that there is a real potential to link tropical and mid to high-latitude paleoenvironmental records. Jensen et al. (in press) Transatlantic correlation of the Alaskan White River Ash. Geology. Pyne-O'Donnell et al. (2012). High-precision ultra-distal Holocene tephrochronology in North America. Quaternary Science Reviews, 52, 6-11. Swindles et al. (2011). A 7000 yr perspective on volcanic ash clouds affecting northern Europe. Geology, 39, 887-890.

Atmospheric Pressure DC Plasma Processing of TIO2/PEDOT:PSS Nanocomposites

In this work we demonstrate the synthesis of a TiO2/PEDOT:PSS nanocomposite material in aqueous solution through atmospheric pressure direct current (DC) plasma processing at room temperature. The dispersion of the TiO2 nanoparticles is enhanced after microplasma processing, and TiO2/polymer hybrid nanoparticles with a distinct core shell structure have been obtained. We have observed increased TiO2/PEDOT:PSS nanocomposite electrical conductivity due to microplasma processing. The improvement in nanocomposite properties is due to the enhanced dispersion and stability in liquid polymer of microplasma treated TiO2 nanoparticles. Both plasma induced surface charge and nanoparticle surface termination with specific plasma chemical species are thought to provide an enhanced barrier to nanoparticle agglomeration and promote nanoparticle-polymer bonding, which is expected to have a significant benefit in materials processing with inorganic nanoparticles for wide range of applications.

Parasite neuropeptide biology:Seeding rational drug target selection?

The rationale for identifying drug targets within helminth neuromuscular signalling systems is based on the premise that adequate nerve and muscle function is essential for many of the key behavioural determinants of helminth parasitism, including sensory perception/host location, invasion, locomotion/orientation, attachment, feeding and reproduction. This premise is validated by the tendency of current anthelmintics to act on classical neurotransmitter-gated ion channels present on helminth nerve and/or muscle, yielding therapeutic endpoints associated with paralysis and/or death. Supplementary to classical neurotransmitters, helminth nervous systems are peptide-rich and encompass associated biosynthetic and signal transduction components - putative drug targets that remain to be exploited by anthelmintic chemotherapy. At this time, no neuropeptide system-targeting lead compounds have been reported, and given that our basic knowledge of neuropeptide biology in parasitic helminths remains inadequate, the short-term prospects for such drugs remain poor. Here, we review current knowledge of neuropeptide signalling in Nematoda and Platyhelminthes, and highlight a suite of 19 protein families that yield deleterious phenotypes in helminth reverse genetics screens. We suggest that orthologues of some of these peptidergic signalling components represent appealing therapeutic targets in parasitic helminths.

Testing two different doses of tiotropium Respimat® in cystic fibrosis: Phase 2 randomized trial results

Background: Tiotropium is a once-daily, long-acting anticholinergic bronchodilator with the potential to alleviate airway obstruction in cystic fibrosis. Our objective was to evaluate the efficacy and safety of 2.5 and 5 μg once-daily tiotropium delivered via the Respimat Soft Mist Inhaler vs. placebo in people with cystic fibrosis. Methods: This phase 2, 12-week, randomized, double-blind, placebo-controlled parallel-group study of tiotropium Respimat as add-on to usual cystic fibrosis maintenance therapy included people with cystic fibrosis with pre-bronchodilator forced expiratory volume in 1 second (FEV₁) ≥25% predicted. Co-primary efficacy end points were change from baseline in percent-predicted FEV₁area under the curve from 0 to 4 hours (FEV₁AUC_0-4h), and trough FEV₁at the end of week 12. Findings: A total of 510 subjects with cystic fibrosis aged 5-69 years were randomized. Both doses of tiotropium resulted in significant improvement compared with placebo in the co-primary efficacy end points at the end of week 12 (change from baseline in percent-predicted FEV₁AUC_0-4h: 2.5 μg: 2.94%, 95% confidence interval 1.19-4.70, p = 0.001; 5 μg: 3.39%, 95% confidence interval 1.67-5.12, p = 0.0001; in percent-predicted trough FEV₁:2.5 μg: 2.24%, p = 0.2; 5 μg: 2.22%, p = 0.02). There was a greater benefit with tiotropium 5 vs. 2.5 μg. No treatment-related adverse events or unexpected safety findings were observed in patients taking tiotropium. Conclusions: Tiotropium significantly improved lung function in people with cystic fibrosis. The improvement was greater with the higher dose than the lower dose, with no difference in adverse events.

Adiposity as a cause of cardiovascular disease: a Mendelian randomization study

Background: Adiposity, as indicated by body mass index (BMI), has been associated with risk of cardiovascular diseases in epidemiological studies. We aimed to investigate if these associations are causal, using Mendelian randomization (MR) methods.

Methods: The associations of BMI with cardiovascular outcomes [coronary heart disease (CHD), heart failure and ischaemic stroke], and associations of a genetic score (32 BMI single nucleotide polymorphisms) with BMI and cardiovascular outcomes were examined in up to 22 193 individuals with 3062 incident cardiovascular events from nine prospective follow-up studies within the ENGAGE consortium. We used random-effects meta-analysis in an MR framework to provide causal estimates of the effect of adiposity on cardiovascular outcomes.

Results: There was a strong association between BMI and incident CHD (HR = 1.20 per SD-increase of BMI, 95% CI, 1.12–1.28, P = 1.9·10−7), heart failure (HR = 1.47, 95% CI, 1.35–1.60, P = 9·10−19) and ischaemic stroke (HR = 1.15, 95% CI, 1.06–1.24, P = 0.0008) in observational analyses. The genetic score was robustly associated with BMI (β = 0.030 SD-increase of BMI per additional allele, 95% CI, 0.028–0.033, P = 3·10−107). Analyses indicated a causal effect of adiposity on development of heart failure (HR = 1.93 per SD-increase of BMI, 95% CI, 1.12–3.30, P = 0.017) and ischaemic stroke (HR = 1.83, 95% CI, 1.05–3.20, P = 0.034). Additional cross-sectional analyses using both ENGAGE and CARDIoGRAMplusC4D data showed a causal effect of adiposity on CHD.

Conclusions: Using MR methods, we provide support for the hypothesis that adiposity causes CHD, heart failure and, previously not demonstrated, ischaemic stroke.

Ophthalmic epidemiology in Europe: the “European Eye Epidemiology” (E3) consortium

The European Eye Epidemiology (E3) consortium is a recently formed consortium of 29 groups from 12 European countries. It already comprises 21 population-based studies and 20 other studies (case-control, cases only, randomized trials), providing ophthalmological data on approximately 170,000 European participants. The aim of the consortium is to promote and sustain collaboration and sharing of data and knowledge in the field of ophthalmic epidemiology in Europe, with particular focus on the harmonization of methods for future research, estimation and projection of frequency and impact of visual outcomes in European populations (including temporal trends and European subregions), identification of risk factors and pathways for eye diseases (lifestyle, vascular and metabolic factors, genetics, epigenetics and biomarkers) and development and validation of prediction models for eye diseases. Coordinating these existing data will allow a detailed study of the risk factors and consequences of eye diseases and visual impairment, including study of international geographical variation which is not possible in individual studies. It is expected that collaborative work on these existing data will provide additional knowledge, despite the fact that the risk factors and the methods for collecting them differ somewhat among the participating studies. Most studies also include biobanks of various biological samples, which will enable identification of biomarkers to detect and predict occurrence and progression of eye diseases. This article outlines the rationale of the consortium, its design and presents a summary of the methodology.