Antipsychotics and Torsadogenic Risk: Signals Emerging from the US FDA Adverse Event Reporting System Database

Background: Drug-induced torsades de pointes (TdP) and related clinical entities represent a current regulatory and clinical burden. Objective: As part of the FP7 ARITMO (Arrhythmogenic Potential of Drugs) project, we explored the publicly available US FDA Adverse Event Reporting System (FAERS) database to detect signals of torsadogenicity for antipsychotics (APs). Methods: Four groups of events in decreasing order of drug-attributable risk were identified: (1) TdP, (2) QT-interval abnormalities, (3) ventricular fibrillation/tachycardia, and (4) sudden cardiac death. The reporting odds ratio (ROR) with 95 % confidence interval (CI) was calculated through a cumulative analysis from group 1 to 4. For groups 1+2, ROR was adjusted for age, gender, and concomitant drugs (e.g., antiarrhythmics) and stratified for AZCERT drugs, lists I and II (http://www.azcert.org, as of June 2011). A potential signal of torsadogenicity was defined if a drug met all the following criteria: (a) four or more cases in group 1+2; (b) significant ROR in group 1+2 that persists through the cumulative approach; (c) significant adjusted ROR for group 1+2 in the stratum without AZCERT drugs; (d) not included in AZCERT lists (as of June 2011). Results: Over the 7-year period, 37 APs were reported in 4,794 cases of arrhythmia: 140 (group 1), 883 (group 2), 1,651 (group 3), and 2,120 (group 4). Based on our criteria, the following potential signals of torsadogenicity were found: amisulpride (25 cases; adjusted ROR in the stratum without AZCERT drugs = 43.94, 95 % CI 22.82-84.60), cyamemazine (11; 15.48, 6.87-34.91), and olanzapine (189; 7.74, 6.45-9.30). Conclusions: This pharmacovigilance analysis on the FAERS found 3 potential signals of torsadogenicity for drugs previously unknown for this risk

SMOD - Data Augmentation Based on Statistical Models of Deformation to Enhance Segmentation in 2D Cine Cardiac MRI

Deep learning has revolutionized medical image analysis in recent years. Nevertheless, technical, ethical and financial constraints along with confidentiality issues still limit data availability, and therefore the performance of these approaches. To overcome such limitations, data augmentation has proven crucial. Here we propose SMOD, a novel augmentation methodology based on Statistical Models of Deformations, to segment 2D cine scans in cardiac MRI. In brief, the shape variability of the training set space is modelled so new images with the appearance of the original ones but unseen shapes within the space of plausible realistic shapes are generated. SMOD is compared to standard augmentation providing quantitative improvement, especially when the training data available is very limited or the structures to segment are complex and highly variable. We finally propose a state-of-art, deep learning 2D cardiac MRI segmenter for normal and hypertrophic cardiomyopathy hearts with an epicardium and endocardium mean Dice score of 0.968 in short and long axis.</p

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Design of Packaging Vents for Cooling Fresh Horticultural Produce

Abstract This review focuses on the design of vents in packages used for handling horticulture produce. The studies on vent designs that are conducted to obtain fundamental understanding of the mechanisms by which different parameters affect the rate and homogeneity of the airflow and the cooling process are presented. Ventilated packages should be designed in such a way that they can provide a uniform airflow distribution and consequently uniform produce cooling. Total opening area and opening size and position show a significant effect on pressure drop, air distribution uniformity and cooling efficiency. Recent advances in measurement and mathematical modelling techniques have provided powerful tools to develop detailed investigations of local airflow rate and heat and mass transfer processes within complex packaging structures. The complexity of the physical structure of the packed systems and the biological variability of the produce make both experimental and model-based studies of transport processes challenging. In many of the available mathematical models, the packed structure is assumed as a porous medium; the limitations of the porous media approach are evident during vented package design studies principally when the containerto-produce dimension ratio is below a certain value. The complex and chaotic structure within horticultural produce ventilated packages during a forced-air precooling process complicates the numerical study of energy and mass transfer considering each individual produce. Future research efforts should be directed to detailed models of the vented package, the complex produce stacking within the package, as well as their interaction with adjacent produce, stacks and surrounding environment. For the validation of the numerical models, the development of better experimental techniques taking into account the complex packaging system is also very important

Waveshifters and Scintillators for Ionizing Radiation Detection

Scintillation and waveshifter materials have been developed for the detection of ionizing radiation in an STTR program between Ludlum Measurements, Inc. and the University of Notre Dame. Several new waveshifter materials have been developed which are comparable in efficiency and faster in fluorescence decay than the standard material Y11 (K27) used in particle physics for several decades. Additionally, new scintillation materials useful for fiber tracking have been developed which have been compared to 3HF. Lastly, work was done on developing liquid scintillators and paint-on scintillators and waveshifters for high radiation environments

Impact of shrub branches on the shortwave vertical irradiance profile in snow

In the Arctic, shrubs are expanding and are covered by snow most of the year. Shrub branches buried in snow absorb solar radiation, reducing irradiance. This modifies the profile of radiative energy absorption in the snowpack and therefore its temperature gradient and metamorphism. Perhaps more importantly, it also reduces photochemical reaction rates and the emission of reactive and climatically active molecules to the atmosphere. No study is currently available to quantify the reduction in photochemical rates caused by shrubs buried in snow. Here, we monitor irradiance in the photochemically active range using a filter at 390 ± 125 nm in snow-covered Alnus incana (gray alders) shrubs in the boreal forest near Université Laval and on nearby grassland during a whole winter by placing light sensors at fixed heights in shrubs and on grassland and observed that irradiance in shrubs was greatly reduced. We performed radiative transfer simulations, testing the hypothesis that shrub branches behave as homogeneous absorbers such as soot. At 390 nm, dense shrub branches reduce irradiance similarly to about 140 ppb of soot. Since ice is much more absorbent at longer wavelengths, we also used a filter to monitor the 715–1000 nm wavelengths (effective 760 nm) to investigate the spectral dependence of shrub impacts on radiative energy absorption. Because of competing ice absorption at 760 nm, the effect of shrubs was much weaker than at 390 nm. We calculate that a high branch density will reduce photochemical reaction rates integrated over the whole snowpack by about a factor of 2. This may affect the composition of the lower-Arctic atmosphere in winter and spring in numerous ways, including a lower oxidative capacity, lower level of nitrogen oxides and modified secondary aerosol production. Climatic effects are expected from these compositional changes.</p

Single T Cell Sequencing Demonstrates the Functional Role alpha beta TCR Pairing in Cell Lineage and Antigen Specificity

Although structural studies of individual T cell receptors (TCRs) have revealed important roles for both the alpha and beta chain in directing MHC and antigen recognition, repertoire-level immunogenomic analyses have historically examined the beta chain alone. To determine the amount of useful information about TCR repertoire function encoded within alpha beta pairings, we analyzed paired TCR sequences from nearly 100,000 unique CD4+ and CD8+ T cells captured using two different high-throughput, single-cell sequencing approaches. Our results demonstrate little overlap in the healthy CD4+ and CD8+ repertoires, with shared TCR sequences possessing significantly shorter CDR3 sequences corresponding to higher generation probabilities. We further utilized tools from information theory and machine learning to show that while alpha and beta chains are only weakly associated with lineage, of pairings appear to synergistically drive TCR-MHC interactions. V alpha beta gene pairings were found to be the TCR feature most informative of T cell lineage, supporting the existence of germline-encoded paired alpha beta TCR-MHC interaction motifs. Finally, annotating our TCR pairs using a database of sequences with known antigen specificities, we demonstrate that approximately a third of the T cells possess alpha and beta chains that each recognize different known antigens, suggesting that alpha beta pairing is critical for the accurate inference of repertoire functionality. Together, these findings provide biological insight into the functional implications of alpha beta pairing and highlight the utility of single-cell sequencing in immunogenomics