Crib death: Further support for the concept of fatal cardiac electrical instability as the final common pathway

This work intends to be a review of the current status of knowledge on the cardiac conduction system in the crib death as well as remaining challenges, including reflections upon authors' personal works as well as many studies by others. The cardiac conduction system findings of resorptive degeneration, His bundle dispersion, Mahaim fibers, cartilaginous meta-hyperplasia, persistent fetal dispersion, left sided His bundle, hemorrhage of the atrio-ventricular junction, septation of the bifurcation, atrio-ventricular node dispersion, sinus node hypoplasia, Zahn node, His bundle hypoplasia, atrio-ventricular node and His bundle dualism are hereby discussed by the authors. The cardiac hypotheses postulating that crib death could be due to lethal cardiac arrhythmias or heart block were considered of great interest in the 1970s. After a general abandon of the conduction studies in crib death, the cardiac concept of crib death is gathering a renewed interest, as well as the occurrence of infantile junctional tachycardia. Both the morphological and functional derangement underlying crib death remain poorly understood, assuring that it remains to be a major medical and social problem. Despite the non-specificity of most of the cardiac conduction findings in crib death, we believe that they, in association with altered neurovegetative stimuli, could underlie potentially malignant arrhythmias, providing a morphologic support for the cardiac concept of crib death

Multifocal cardiac Purkinje cell tumor in infancy

Cot death is the commonest form of death among babies in the first year of life. The authors report the unusual case of a 2-month-old female infant dying suddenly and unexpectedly in whom a postmortem histological examination demonstrated a cardiac multifocal Purkinje cell tumor. Necroscopy studies of sudden infant death should always include an accurate histological examination of the cardiac conduction system and brainstem using serial sections

The potential of small unmanned aircraft systems and structure-from-motion for topographic surveys: a test of emerging integrated approaches at Cwm Idwal, North Wales

This paper was accepted for publication in the journal Geomorphology and the definitive published version is available at http://dx.doi.org/10.1016/j.geomorph.2014.07.021Novel topographic survey methods that integrate both structure-from-motion (SfM) photogrammetry and small unmanned aircraft systems (sUAS) are a rapidly evolving investigative technique. Due to the diverse range of survey configurations available and the infancy of these new methods, further research is required. Here, the accuracy, precision and potential applications of this approach are investigated. A total of 543 images of the Cwm Idwal moraine–mound complex were captured from a light (b5 kg) semi-autonomous multi-rotor unmanned aircraft system using a consumer-grade 18 MP compact digital camera. The imageswere used to produce a DSM(digital surfacemodel) of themoraines. The DSMis in good agreement with 7761 total station survey points providing a total verticalRMSE value of 0.517mand verticalRMSE values as lowas 0.200mfor less densely vegetated areas of the DSM. High-precision topographic data can be acquired rapidly using this technique with the resulting DSMs and orthorectified aerial imagery at sub-decimetre resolutions. Positional errors on the total station dataset, vegetation and steep terrain are identified as the causes of vertical disagreement. Whilst this aerial survey approach is advocated for use in a range of geomorphological settings, care must be taken to ensure that adequate ground control is applied to give a high degree of accuracy

Simplified footprint-free Cas9/CRISPR editing of cardiac-associated genes in human pluripotent stem cells

Modelling disease with hPSCs is hindered because the impact on cell phenotype from genetic variability between individuals can be greater than from the pathogenic mutation. While ‘footprint-free’ Cas9/CRISPR editing solves this issue, existing approaches are inefficient or lengthy. Here, a simplified PiggyBac strategy shortened hPSC editing by 2 weeks and required one round of clonal expansion and genotyping rather than two, with similar efficiencies to the longer conventional process. Success was shown across 4 cardiac-associated loci (ADRB2, GRK5, RYR2, ACTC1) by genomic cleavage and editing efficiencies of 8-93% and 8-67%, respectively, including mono- and/or bi-allelic events. Pluripotency was retained, as was differentiation into high purity cardiomyocytes (CMs; 88-99%). Using the GRK5 isogenic lines as an exemplar, chronic stimulation with the beta-adrenoceptor agonist, isoprenaline, reduced beat rate in hPSC-CMs expressing GRK5-Q41 but not GRK5-L41; this was reversed by the beta-blocker, propranolol. This shortened, footprint-free approach will be useful for mechanistic studies

Reconstruction of former glacier surface topography from archive oblique aerial images

Archive oblique aerial imagery offers the potential to reconstruct the former geometry of valley glaciers and other landscape surfaces. Whilst the use of Structure-from-Motion (SfM) photogrammetry with multiview stereopsis (MVS) to process small-format imagery is now well established in the geosciences, the potential of the technique for extracting topographic data from archive oblique aerial imagery is unclear. Here, SfM-MVS is used to reconstruct the former topography of two high-Arctic glaciers (Midtre and Austre Lovénbreen, Svalbard, Norway) using three archive oblique aerial images obtained by the Norwegian Polar Institute in 1936. The 1936 point cloud was produced using seven LiDAR-derived ground control points located on stable surfaces in proximity to the former piedmont glacier termini. To assess accuracy, the 1936 data set was compared to a LiDAR data set using the M3C2 algorithm to calculate cloud-to-cloud differences. For stable areas (such as nonglacial surfaces), vertical differences were detected between the two point clouds (RMS M3C2 vertical difference of 8.5 m), with the outwash zones adjacent to the assessed glacier termini showing less extensive vertical discrepancies (94% of M3C2 vertical differences between ±5 m). This research highlights that historical glacier surface topography can be extracted from archive oblique aerial imagery, but accuracy is limited by issues including the lack of camera calibration, the quality and resolution of the archive imagery, and by the identification of suitable ground control. To demonstrate the value of historical glacier surfaces produced using oblique archive imagery, the reconstructed glacier surface topography is used to investigate evidence of a potential former surge front at the high-Arctic valley glacier, Austre Lovénbreen - a glacier identified to have potentially exhibited surge-type behaviour during the Neoglacial. A surface bulge of ~15–20 m is resolved on the 1936 model; however, when compared with the now deglaciated former subglacial topography, a surge origin for the surface feature becomes unclear. The processed 1936 oblique imagery was also used to produce orthorectified nadir aerial imagery, from which structural mapping was undertaken: this adds to the existing 1948–1995 structural map series for these glaciers. This research demonstrates the potential of SfM-MVS for reconstructing historical glacier surfaces, which is important for aiding our understanding of former glacier dynamics and enabling the rapid assessment of glacier change over time

Ice-cored moraine degradation mapped and quantified using an unmanned aerial vehicle: a case study from a polythermal glacier in Svalbard

Ice-cored lateral–frontal moraines are common at the margins of receding high-Arctic valley glaciers, but the preservation potential of these features within the landform record is unclear. Recent climatic amelioration provides an opportunity to study the morphological evolution of these landforms as they de-ice. This is important because high-Arctic glacial landsystems have been used as analogues for formerly glaciated areas in the mid-latitudes. This study uses SfM (Structure-from-Motion) photogrammetry and a combination of archive aerial and UAV (unmanned aerial vehicle) derived imagery to investigate the degradation of an ice-cored lateral–frontal moraine at Austre Lovénbreen, Svalbard. Across the study area as a whole, over an 11-year period, the average depth of surface lowering was − 1.75 ± 0.89 m. The frontal sections of the moraine showed low or undetectable rates of change. Spatially variable rates of surface lowering are associated with differences in the quantity of buried ice within the structure of the moraine. Morphological change was dominated by surface lowering, with limited field evidence of degradation via back-wastage. This permits the moraine a greater degree of stability than previously observed at other sites in Svalbard. It is unclear whether the end point will be a fully stabilised ice-cored moraine, in equilibrium with its environment, or an ice-free lateral–frontal moraine complex. Controls on geomorphological change (e.g. topography and climate) and the preservation potential of the lateral–frontal moraine are discussed. The methods used by this research also demonstrate the potential value of SfM photogrammetry and unmanned aerial vehicles for monitoring environmental change and are likely to have wider applications in other geoscientific sub-disciplines

Measurement of the splashback feature around SZ-selected Galaxy clusters with DES, SPT, and ACT

We present a detection of the splashback feature around galaxy clusters selected using the Sunyaev–Zel’dovich (SZ) signal. Recent measurements of the splashback feature around optically selected galaxy clusters have found that the splashback radius, rsp, is smaller than predicted by N-body simulations. A possible explanation for this discrepancy is that rsp inferred from the observed radial distribution of galaxies is affected by selection effects related to the optical cluster-finding algorithms. We test this possibility by measuring the splashback feature in clusters selected via the SZ effect in data from the South Pole Telescope SZ survey and the Atacama Cosmology Telescope Polarimeter survey. The measurement is accomplished by correlating these cluster samples with galaxies detected in the Dark Energy Survey Year 3 data. The SZ observable used to select clusters in this analysis is expected to have a tighter correlation with halo mass and to be more immune to projection effects and aperture-induced biases, potentially ameliorating causes of systematic error for optically selected clusters. We find that the measured rsp for SZ-selected clusters is consistent with the expectations from simulations, although the small number of SZ-selected clusters makes a precise comparison difficult. In agreement with previous work, when using optically selected redMaPPer clusters with similar mass and redshift distributions, rsp is ∼2σ smaller than in the simulations. These results motivate detailed investigations of selection biases in optically selected cluster catalogues and exploration of the splashback feature around larger samples of SZ-selected clusters. Additionally, we investigate trends in the galaxy profile and splashback feature as a function of galaxy colour, finding that blue galaxies have profiles close to a power law with no discernible splashback feature, which is consistent with them being on their first infall into the cluster

Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of l

DES Y3 + KiDS-1000: Consistent cosmology combining cosmic shear surveys

We present a joint cosmic shear analysis of the Dark Energy Survey (DES Y3) and the Kilo-Degree Survey (KiDS-1000) in a collaborative effort between the two survey teams. We find consistent cosmological parameter constraints between DES Y3 and KiDS-1000 which, when combined in a joint-survey analysis, constrain the parameter $S_8 = \sigma_8 \sqrt{\Omega_{\rm m}/0.3}$ with a mean value of $0.790^{+0.018}_{-0.014}$. The mean marginal is lower than the maximum a posteriori estimate, $S_8=0.801$, owing to skewness in the marginal distribution and projection effects in the multi-dimensional parameter space. Our results are consistent with $S_8$ constraints from observations of the cosmic microwave background by Planck, with agreement at the $1.7\sigma$ level. We use a Hybrid analysis pipeline, defined from a mock survey study quantifying the impact of the different analysis choices originally adopted by each survey team. We review intrinsic alignment models, baryon feedback mitigation strategies, priors, samplers and models of the non-linear matter power spectrum.Comment: 38 pages, 21 figures, 15 tables, submitted to the Open Journal of Astrophysics. Watch the core team discuss this analysis at https://cosmologytalks.com/2023/05/26/des-kid

Large-Eddy Simulations of Magnetohydrodynamic Turbulence in Heliophysics and Astrophysics

We live in an age in which high-performance computing is transforming the way we do science. Previously intractable problems are now becoming accessible by means of increasingly realistic numerical simulations. One of the most enduring and most challenging of these problems is turbulence. Yet, despite these advances, the extreme parameter regimes encountered in space physics and astrophysics (as in atmospheric and oceanic physics) still preclude direct numerical simulation. Numerical models must take a Large Eddy Simulation (LES) approach, explicitly computing only a fraction of the active dynamical scales. The success of such an approach hinges on how well the model can represent the subgrid-scales (SGS) that are not explicitly resolved. In addition to the parameter regime, heliophysical and astrophysical applications must also face an equally daunting challenge: magnetism. The presence of magnetic fields in a turbulent, electrically conducting fluid flow can dramatically alter the coupling between large and small scales, with potentially profound implications for LES/SGS modeling. In this review article, we summarize the state of the art in LES modeling of turbulent magnetohydrodynamic (MHD) ows. After discussing the nature of MHD turbulence and the small-scale processes that give rise to energy dissipation, plasma heating, and magnetic reconnection, we consider how these processes may best be captured within an LES/SGS framework. We then consider several special applications in heliophysics and astrophysics, assessing triumphs, challenges,and future directions