An estimate of the dispersion of repolarization times based on a biophysical model of the ECG

Temporal heterogeneity of ventricular repolarization is a key quantity for the development of ventricular reentrant arrhythmia. In this paper, we introduce the V-index, a novel ECG-based estimator of the standard deviation of ventricular myocytes' repolarization times s(?). Differently from other ECG metrics of repolarization heterogeneity, the V-index was derived from the analysis of a biophysical model of the ECG, where repolarization is described by the dominant T-wave (DTW) paradigm. The model explains the shape of T-waves in each lead as a projection of a main waveform (the DTW) and its derivatives weighted by scalars, the lead factors. A mathematical formula is derived to link the heterogeneity of ventricular repolarization s(?) and the V-index. The formula was verified using synthetic 12-lead ECGs generated with a direct electrophysiological model for increasing values of s(?) (in the range 20-70 ms). A linear relationship between the V-index and s(?) was observed, V ≈ 0.675 s(?) + 1.8 ms (R(2) = 0.9992). Finally, 68 ECGs from the E-OTH-12-0068-010 database of the Telemetric and Holter ECG Warehouse were analyzed. The V-index coherently increased after sotalol administration, a drug known to have QT-prolonging potential (p < 0.001).     

Textureless macula swelling detection with multiple retinal fundus images

Retinal fundus images acquired with nonmydriatic digital fundus cameras are versatile tools for the diagnosis of various retinal diseases. Because of the ease of use of newer camera models and their relatively low cost, these cameras can be employed by operators with limited training for telemedicine or point-of-care (PoC) applications. We propose a novel technique that uses uncalibrated multiple-view fundus images to analyze the swelling of the macula. This innovation enables the detection and quantitative measurement of swollen areas by remote ophthalmologists. This capability is not available with a single image and prone to error with stereo fundus cameras. We also present automatic algorithms to measure features from the reconstructed image, which are useful in PoC automated diagnosis of early macular edema, e.g., before the appearance of exudation. The technique presented is divided into three parts: first, a preprocessing technique simultaneously enhances the dark microstructures of the macula and equalizes the image; second, all available views are registered using nonmorphological sparse features; finally, a dense pyramidal optical flow is calculated for all the images and statistically combined to build a naive height map of the macula. Results are presented on three sets of synthetic images and two sets of real-world images. These preliminary tests show the ability to infer a minimum swelling of 300 μm and to correlate the reconstruction with the swollen location.     

Intestinal passage of microencapsulated fish oil in rats following oral administration

Fish oil labelled with [(14)C-linolenin] tracer was orally administered by gavage as an oil-water mixture (free oil) or as an oil-in-water emulsion formulation (microencapsulated oil) to fasted rats. Groups of rats were then given food after gavage or alternatively not fed to examine the effect of food on intestinal passage. Feeding after gavage drives lumenal free oil faster through the gastrointestinal (GI) tract. Microencapsulation slows down the lumenal progression in the GI tract with feeding. Non-feeding also slows down the lumenal progress of free oil in the GI tract but this is not influenced by microencapsulation. Analysis of the relative distribution of the label along the GI tract tissue wall showed that the upper small intestine was the main site of label accumulation in the GI tract. Of the oil that remained in the lumen, there was slight protection against early uptake and metabolism in the stomach and upper GI tract in rats that were either fed or not fed after dosing when microencapsulated oil was administered. Microencapsulation increased the levels of radiolabel in the liver and blood. The primary organ for accumulation of radiolabel for both free and microencapsulated oils in rats that were fed or fasted after dosing was the liver.     

Structural analysis of intact monoclonal antibodies by electron transfer dissociation mass spectrometry

Improving qualitative and quantitative characterization of monoclonal antibodies is essential, because of their increasing popularity as therapeutic drug targets. Electron transfer dissociation (ETD)-based top-down mass spectrometry (MS) is the method of choice for in-depth characterization of post-translationally modified large peptides, small- and medium-sized proteins, and noncovalent protein complexes. Here, we describe the performance of ETD-based top-down mass spectrometry for structural analysis of intact 150 kDa monoclonal antibodies, immunoglobulins G (IgGs). Simultaneous mass analysis of intact IgGs as well as a complex mixture of ETD product ions at sufficiently high resolution and mass accuracy in a wide m/z range became possible because of recent advances in state-of-the-art time-of-flight (TOF) mass spectrometry. High-resolution ETD TOF MS performed on IgG1-kappa from murine myeloma cells and human anti-Rhesus D IgG1 resulted in extensive sequence coverage of both light and heavy chains of IgGs and revealed information on their variable domains. Results are superior and complementary to those previously generated by collision-induced dissociation. However, numerous disulfide bonds drastically reduce the efficiency of top-down ETD fragmentation within the protected sequence regions, leaving glycosylation uncharacterized. Further increases in the experiment sensitivity and improvement of ion activation before and after ETD reaction are needed to target S-S bond-protected sequence regions and post-translational modifications.     

Label-free probing of G-quadruplex formation by surface-enhanced Raman scattering

In this work, we establish the use of surface-enhanced Raman scattering (SERS) as a label-free analytical technique for the direct detection of G-quadruplex formation. In particular, we demonstrate that SERS analysis allows the evaluation of the relative stability of G quadruplexes that differ for the number of G tetrads and investigate several structural features of quadruplexes, such as the orientation of glycosidic bonds, the identification of distortions in the sugar-phosphate backbone, and the degree of hydrogen-bond solvation. Herein, the fluctuation of the SERS spectra, due to the specific interaction of vibrational modes with the SERS-active substrate, is quantitatively analyzed before and after quadruplex formation. The results of this study suggest a perpendicular orientation of the quadruplexes (with or without the 3'-tetra end linker) with respect to the silver colloidal surface, which opens new perspectives for the use of SERS as a label-free analytical tool for the study of the binding mode between quadruplexes and their ligands.     

Hexaferrite/polyethylene composite coatings prepared with flame spraying

Composite coatings from different volume ratios of hexaferrite (BaFe₁₂O₁₉ or SrFe₁₂O₁₉) and polyethylene were prepared, for the first time, with flame spraying. The hexaferrite phase retained its crystal structure and microstructure during the process, while the polyethylene melted and resolidified. The coatings showed magnetic hysteresis loops with high coercivities. The measured electromagnetic behaviour proved that the studied composite coatings would be suitable for electromagnetic wave absorbers in the U-band.     

Strong seasonality produces spatial asynchrony in the outbreak of infectious diseases

Models for infectious diseases usually assume a fixed demographic structure. Yet, a disease can spread over a region encountering different local demographic variations that may significantly alter local dynamics. Spatial heterogeneity in the resulting dynamics can lead to important differences in the design of surveillance and control strategies. We illustrate this by exploring the north–south gradient in the seasonal demography of raccoon rabies over the eastern USA. We find that the greater variance in the timing of spring births characteristic of southern populations can lead to the spatial synchronization of southern epidemics, while the narrow birth-pulse associated with northern populations can lead to an irregular patchwork of epidemics. These results indicate that surveillance in the southern states can be reduced relative to northern locations without loss of detection ability. This approach could yield significant savings in vaccination programmes. The importance of seasonality in many widely distributed diseases indicates that our findings will find applications beyond raccoon rabies.     

米拉列斯·达格利阿布艾——连续性的价值

发现并生存于巴塞罗那旧城(CiutatVella)中心的"新"圣卡泰里娜的市场,就像是聆听某个人有时为了让停顿的争论重新富有生气,引出其他视野,同时向周围的人求助而大声说出来的、活泼而充满好奇的想法。EMBT(恩里克·米拉耶和贝纳德塔·达格利阿布艾)1999年到2005年设计和建造的市场不仅仅是简单而漂亮的建筑,而且是一个微笑的问号,是为了城市及居民的深度思索,是静静地从一个阶段到另一个阶段中寻找过渡建筑的工程之一。     

Assessment of subjective and hemodynamic tolerance of different high‐ and low‐flux dialysis membranes in patients undergoing chronic intermittent hemodialysis: A randomized controlled trial

Clinical experience and experimental data suggest that intradialytic hemodynamic profiles could be influenced by the characteristics of the dialysis membranes. Even within the worldwide used polysulfone family, intolerance to specific membranes was occasionally evoked. The aim of this study was to compare hemodynamically some of the commonly used polysulfone dialyzers in Switzerland. We performed an open‐label, randomized, cross‐over trial, including 25 hemodialysis patients. Four polysulfone dialyzers, A (Revaclear high‐flux, Gambro, Stockholm, Sweden), B (Helixone high‐flux, Fresenius), C (Xevonta high‐flux, BBraun, Melsungen, Germany), and D (Helixone low‐flux, Fresenius, Bad Homburg vor der Höhe, Germany), were compared. The hemodynamic profile was assessed and patients were asked to provide tolerance feedback. The mean score (±SD) subjectively assigned to dialysis quality on a 1–10 scale was A 8.4 ± 1.3, B 8.6 ± 1.3, C 8.5 ± 1.6, D 8.5 ± 1.5. Kt/V was A 1.58 ± 0.30, B 1.67 ± 0.33, C 1.62 ± 0.32, D 1.45 ± 0.31. The low‐ compared with the high‐flux membranes, correlated to higher systolic (128.1 ± 13.1 vs. 125.6 ± 12.1 mmHg, P < 0.01) and diastolic (76.8 ± 8.7 vs. 75.3 ± 9.0 mmHg; P < 0.05) pressures, higher peripheral resistance (1.44 ± 0.19 vs. 1.40 ± 0.18 s × mmHg/mL; P < 0.05) and lower cardiac output (3.76 ± 0.62 vs. 3.82 ± 0.59 L/min; P < 0.05). Hypotension events (decrease in systolic blood pressure by >20 mmHg) were 70 with A, 87 with B, 73 with C, and 75 with D (P < 0.01 B vs. A, 0.05 B vs. C and 0.07 B vs. D). The low‐flux membrane correlated to higher blood pressure levels compared with the high‐flux ones. The Helixone high‐flux membrane ensured the best efficiency. Unfortunately, the very same dialyzer correlated to a higher incidence of hypotensive episodes.