The Role of Cardiovascular Magnetic Resonance in Pediatric Congenital Heart Disease

Cardiovascular magnetic resonance (CMR) has expanded its role in the diagnosis and management of congenital heart disease (CHD) and acquired heart disease in pediatric patients. Ongoing technological advancements in both data acquisition and data presentation have enabled CMR to be integrated into clinical practice with increasing understanding of the advantages and limitations of the technique by pediatric cardiologists and congenital heart surgeons. Importantly, the combination of exquisite 3D anatomy with physiological data enables CMR to provide a unique perspective for the management of many patients with CHD. Imaging small children with CHD is challenging, and in this article we will review the technical adjustments, imaging protocols and application of CMR in the pediatric population

The physics of pulling polyproteins: a review of single molecule force spectroscopy using the AFM to study protein unfolding.

One of the most exciting developments in the field of biological physics in recent years is the ability to manipulate single molecules and probe their properties and function. Since its emergence over two decades ago, single molecule force spectroscopy has become a powerful tool to explore the response of biological molecules, including proteins, DNA, RNA and their complexes, to the application of an applied force. The force versus extension response of molecules can provide valuable insight into its mechanical stability, as well as details of the underlying energy landscape. In this review we will introduce the technique of single molecule force spectroscopy using the atomic force microscope (AFM), with particular focus on its application to study proteins. We will review the models which have been developed and employed to extract information from single molecule force spectroscopy experiments. Finally, we will end with a discussion of future directions in this field

Evidence and modeling of turbulence bifurcation in L-mode confinement transitions on Alcator C-Mod

© 2020 Author(s). Analysis and modeling of rotation reversal hysteresis experiments show that a single turbulent bifurcation is responsible for the Linear to Saturated Ohmic Confinement (LOC/SOC) transition and concomitant intrinsic rotation reversal on Alcator C-Mod. Plasmas on either side of the reversal exhibit different toroidal rotation profiles and therefore different turbulence characteristics despite the profiles of density and temperature, which are indistinguishable within measurement uncertainty. Elements of this bifurcation are also shown to persist for auxiliary heated L-modes. The deactivation of subdominant (in the linear growth rate and contribution to heat transport) ion temperature gradient and trapped electron mode instabilities is identified as the only possible change in turbulence within a reduced quasilinear transport model across the reversal, which is consistent with the measured profiles and inferred heat and particle fluxes. Experimental constraints on a possible change from strong to weak turbulence, outside the description of the quasilinear model, are also discussed. These results indicate an explanation for the LOC/SOC transition that provides a mechanism for the hysteresis through the dynamics of subdominant modes and changes in their relative populations and does not involve a change in the most linearly unstable ion-scale drift-wave instability

Novel modes of rhythmic burst firing at cognitively-relevant frequencies in thalamocortical neurons.

It is now widely accepted that certain types of cognitive functions are intimately related to synchronized neuronal oscillations at both low (alpha/theta) (4-7/8-13 Hz) and high (beta/gamma) (18-35/30-70 Hz) frequencies. The thalamus is a key participant in many of these oscillations, yet the cellular mechanisms by which this participation occurs are poorly understood. Here we describe how, under appropriate conditions, thalamocortical (TC) neurons from different nuclei can exhibit a wide array of largely unrecognised intrinsic oscillatory activities at a range of cognitively-relevant frequencies. For example, both metabotropic glutamate receptor (mGluR) and muscarinic Ach receptor (mAchR) activation can cause rhythmic bursting at alpha/theta frequencies. Interestingly, key differences exist between mGluR- and mAchR-induced bursting, with the former involving extensive dendritic Ca2+ electrogenesis and being mimicked by a non-specific block of K+ channels with Ba2+, whereas the latter appears to be more reliant on proximal Na+ channels and a prominent spike afterdepolarization (ADP). This likely relates to the differential somatodendritic distribution of mGluRs and mAChRs and may have important functional consequences. We also show here that in similarity to some neocortical neurons, inhibiting large-conductance Ca2+-activated K+ channels in TC neurons can lead to fast rhythmic bursting (FRB) at approximately 40 Hz. This activity also appears to rely on a Na+ channel-dependent spike ADP and may occur in vivo during natural wakefulness. Taken together, these results show that TC neurons are considerably more flexible than generally thought and strongly endorse a role for the thalamus in promoting a range of cognitively-relevant brain rhythms

Comparative prebiotic activity of mixtures of cereal grain polysaccharides

The main components of the non-starch polysaccharide (NSP) fraction of wheat flour are arabinoxylan (AX) and β-glucan. These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats. Therefore, it was hypothesised that these NSPs could act synergistically when fermented in vitro at the ratios present in the major foods consumed, resulting in increased prebiotic activity. AX and β-glucan were therefore tested in in vitro fermentation studies to assess their prebiotic activity when used individually and/or in different ratios. Short-chain fatty-acids (SCFAs) produced from in vitro fermentation were measured using HPLC and bacterial populations were measured using flow cytometry with fluorescence in situ hybridisation (Flow-FISH). Fermentation of AX alone resulted in a significant bifidogenic activity and increased concentrations of SCFAs, mainly acetate, after 8-24 h of fermentation, however β-glucan alone did not show prebiotic activity. The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet. This indicates that the population of bacteria in the human GI tract may be modulated by the composition of the fibre in the diet, to maximise the prebiotic potential

Accurate computation of quaternions from rotation matrices

The final publication is available at link.springer.comThe main non-singular alternative to 3×3 proper orthogonal matrices, for representing rotations in R3, is quaternions. Thus, it is important to have reliable methods to pass from one representation to the other. While passing from a quaternion to the corresponding rotation matrix is given by Euler-Rodrigues formula, the other way round can be performed in many different ways. Although all of them are algebraically equivalent, their numerical behavior can be quite different. In 1978, Shepperd proposed a method for computing the quaternion corresponding to a rotation matrix which is considered the most reliable method to date. Shepperd’s method, thanks to a voting scheme between four possible solutions, always works far from formulation singularities. In this paper, we propose a new method which outperforms Shepperd’s method without increasing the computational cost.Peer ReviewedPostprint (author's final draft

Dynamics of trimming the content of face representations for categorization in the brain

To understand visual cognition, it is imperative to determine when, how and with what information the human brain categorizes the visual input. Visual categorization consistently involves at least an early and a late stage: the occipito-temporal N170 event related potential related to stimulus encoding and the parietal P300 involved in perceptual decisions. Here we sought to understand how the brain globally transforms its representations of face categories from their early encoding to the later decision stage over the 400 ms time window encompassing the N170 and P300 brain events. We applied classification image techniques to the behavioral and electroencephalographic data of three observers who categorized seven facial expressions of emotion and report two main findings: (1) Over the 400 ms time course, processing of facial features initially spreads bilaterally across the left and right occipito-temporal regions to dynamically converge onto the centro-parietal region; (2) Concurrently, information processing gradually shifts from encoding common face features across all spatial scales (e.g. the eyes) to representing only the finer scales of the diagnostic features that are richer in useful information for behavior (e.g. the wide opened eyes in 'fear'; the detailed mouth in 'happy'). Our findings suggest that the brain refines its diagnostic representations of visual categories over the first 400 ms of processing by trimming a thorough encoding of features over the N170, to leave only the detailed information important for perceptual decisions over the P300

Population assessment of future trajectories in coronary heart disease mortality.

Background: Coronary heart disease (CHD) mortality rates have been decreasing in Iceland since the 1980s, largely reflecting improvements in cardiovascular risk factors. The purpose of this study was to predict future CHD mortality in Iceland based on potential risk factor trends. Methods and findings: The previously validated IMPACT model was used to predict changes in CHD mortality between 2010 and 2040 among the projected population of Iceland aged 25–74. Calculations were based on combining: i) data on population numbers and projections (Statistics Iceland), ii) population risk factor levels and projections (Refine Reykjavik study), and iii) effectiveness of specific risk factor reductions (published meta-analyses). Projections for three contrasting scenarios were compared: 1) If the historical risk factor trends of past 30 years were to continue, the declining death rates of past decades would level off, reflecting population ageing. 2) If recent trends in risk factors (past 5 years) continue, this would result in a death rate increasing from 49 to 70 per 100,000. This would reflect a recent plateau in previously falling cholesterol levels and recent rapid increases in obesity and diabetes prevalence. 3) Assuming that in 2040 the entire population enjoys optimal risk factor levels observed in low risk cohorts, this would prevent almost all premature CHD deaths before 2040. Conclusions: The potential increase in CHD deaths with recent trends in risk factor levels is alarming both for Iceland and probably for comparable Western populations. However, our results show considerable room for reducing CHD mortality. Achieving the best case scenario could eradicate premature CHD deaths by 2040. Public health policy interventions based on these predictions may provide a cost effective means of reducing CHD mortality in the future

Climate and land-use change during the late Holocene at Lake Ledro (southern Alps, Italy)

International audienceThis paper investigates the relative influences of climatic and anthropogenic factors in explaining environmental and societal changes in the southern Alps, Italy. We investigate a deep sediment core (LL081) from Lake Ledro (652 m a.s.l.). Environmental changes are reconstructed through multiproxy analysis, that is, pollen-based vegetation and climate reconstruction, magnetic susceptibility (MS), lake level, and flood frequency, and the paper focuses on the climate and land-use changes which occurred during the late Holocene. For this time interval, Lake Ledro records high mean water table, increasing amount of pollen-based precipitation, and more erosive conditions. Therefore, while a more humid late Holocene in the southern Alps has the potential to reinforce the forest presence, pollen evidence suggests that anthropogenic activities changed the impact of this regional scenario. Land-use activity (forest clearance for pastoralism, farming, and arboriculture) opened up the large vegetated slopes in the catchment of Lake Ledro, which in turn magnified the erosion related to the change in the precipitation pattern. The record of an almost continuous human occupation for the last 4100 cal. BP is divided into several land-use phases. On the one hand, forest redevelopments on abandoned or less cultivated areas appear to be climatically induced as they occurred in relation with well-known events such as the 2.8-kyr cold event and the ‘Little Ice Age’. On the other hand, climatically independent changes in land use or habitat modes are observed, such as the late-Bronze-Age lake-dwellings abandonment, the human population migration at c. 1600 cal. BP, and the period of the Black Death and famines at 600 cal. BP

A Semi-Lagrangian scheme for a modified version of the Hughes model for pedestrian flow

In this paper we present a Semi-Lagrangian scheme for a regularized version of the Hughes model for pedestrian flow. Hughes originally proposed a coupled nonlinear PDE system describing the evolution of a large pedestrian group trying to exit a domain as fast as possible. The original model corresponds to a system of a conservation law for the pedestrian density and an Eikonal equation to determine the weighted distance to the exit. We consider this model in presence of small diffusion and discuss the numerical analysis of the proposed Semi-Lagrangian scheme. Furthermore we illustrate the effect of small diffusion on the exit time with various numerical experiments