Hemodynamics in the pulmonary bifurcation : effect of geometry and boundary conditions

Introduction Pulmonary regurgitation [1] and obstruction in the left pulmonary artery [2], the most common complications affecting adult patients with repaired tetralogy of Fallot, are known to lead to right ventricular dilatation and dysfunction. Long-term pulmonary stenosis is also hypothesized to lead to abnormal lung development and elevated pulmonary vascular resistance [3]. Pulmonary valve replacement is deemed necessary in these patients, but the optimal timing to perform the surgery is still ambiguous [1]. The aim of this study is to numerically investigate the blood flow development in the pulmonary bifurcation of adult patients with congenital heart defects. In this work, we present results from a parametric analysis, where the effect of geometry (branch angle, origin, branch obstruction) and boundary conditions (unsteady flow, Reynolds number, pressure difference at the outlets, and non-Newtonian models) were examined. Methods Blood flow simulations were performed in simplified models of the pulmonary bifurcation, using a validated finite volume scheme in OpenFOAM®. Physiological and pathological conditions were assumed and local velocities, wall shear stress values, velocity and pressure distributions were evaluated. The fluid was considered incompressible and governed by the Newtonian Navier-Stokes equations. The Power Law, CrossPower Law, the Casson, and the Bird-Carreau non-Newtonian models were also investigated. Results & Discussion Blood flow in the pulmonary bifurcation is highly dependent on the local geometrical characteristics and the boundary conditions assumed. Flow separation increases with the branching angle, the branch origin, and stenosis. Branch obstruction and boundary conditions have, further, a significant effect on velocities and shear stresses developed on the vessel wall. The presence of peripheral stenosis and pressure difference at the branch outlets affects significantly the flow splits in the daughter branches. Finally, pressure ratios are considered to provide a good indication of flow discrepancies between the different cases tested. Evaluation of the results on more complex 3D anatomically-correct geometries is necessary. Future work will involve reconstruction of patient-specific models using CT and MRI data from adult patients with congenital heart diseases. More realistic boundary conditions will also be considered, including the pulsatile nature of blood flow and Windkessel models at the branch outlets to account for peripheral resistance. Conclusion Computational fluid dynamics tools have been utilised in this study to investigate the effect of a range of different geometrical characteristics and boundary conditions. The main findings of this study concern a new effect of the branch origin, and a notable branch flow split analysis under conditions of peripheral stenosis and pressure difference in the branch outlets. Acknowledgments This work is supported in part by the University of Strathclyde Research Studentship Scheme (SRSS) Research Excellence Awards (REA), Project No 1208 and the European Union’s Horizon 2020 research and innovation programme, under the Marie Skłodowska-Curie grant agreement No 749185. References 1. Kogon B.E. et al. Seminars in Thoracic and Cardiovascular Surgery 2015; 27:57-64. 2. McElhinney D.B. et al. The Annals of Thoracic Surgery 1998; 65:1120-1126. 3. Harris M.A. et al. Cardiovascular Imaging 2011; 4:506-513

Constraints on the cosmic string loop collapse fraction from primordial black holes

A small fraction, f , of cosmic string loops can collapse to form Primordial Black Holes (PBHs). Constraints on the abundance of PBHs can therefore be used to constrain f. We update these calculations, taking into account the PBH extended mass function, and find f < 10 −31 (Gµ/c 2) ^−3/2. This is roughly one order of magnitude tighter than previous constraints. The improvement from the tighter constraints on the abundance of PBHs is partly offset by refinements to the theoretical calculation of the cosmic string loop formation rate

Phylobioactive hotspots in plant resources used to treat Chagas disease

Globally, more than six million people are infected with Trypanosoma cruzi, the causative protozoan parasite of the vector-borne Chagas disease (CD). We conducted a cross-sectional ethnopharmacological field study in Bolivia among different ethnic groups where CD is hyperendemic. A total of 775 extracts of botanical drugs used in Bolivia in the context of CD and botanical drugs from unrelated indications from the Mediterranean De Materia Medica compiled by Dioscorides two thousand years ago were profiled in a multidimensional assay uncovering different antichagasic natural product classes. Intriguingly, the phylobioactive anthraquinone hotspot matched the antichagasic activity of Senna chloroclada, the taxon with the strongest ethnomedical consensus for treating CD among the Izoceño-Guaraní. Testing common 9,10-anthracenedione derivatives in T. cruzi cellular infection assays demarcates hydroxyanthraquinone as a potential antichagasic lead scaffold. Our study systematically uncovers in vitro antichagasic phylogenetic hotspots in the plant kingdom as a potential resource for drug discovery based on ethnopharmacological hypotheses

Blood flow simulations in models of the pulmonary bifurcation to facilitate treatment of adults with congenital heart disease

Tetralogy of Fallot (ToF) is the most common cyanotic congenital heart disease, for which patients require surgical intervention at a very young age. Although these patients have long survival rates, they are at risk of chronic complications and frequently require re-operations with the most common being pulmonary valve replacement (PVR). However, the decision for surgical intervention is currently based on clinical indications and the right timing for PVR remains ambiguous [1,2]. The overall objective of this work is to identify a computational metric that will help assess the right timing for surgical intervention in adults with repaired tetralogy of Fallot. This current study concerns a preliminary computational analysis of blood flow in simplified geometries of the pulmonary bifurcation. The focus lies on the effect of geometric and haemodynamic parameters on the wall shear stress patterns around the pulmonary bifurcation

“I didn’t have any option”: Experiences of people receiving in-centre haemodialysis during the COVID-19 pandemic

People receiving in-centre haemodialysis (ICHD) during the COVID-19 pandemic had to adjust to more challenging treatment conditions. To explore people’s experiences of adjustment to ICHD during the pandemic. Thematic analysis of in-depth, semi-structured interviews with 14 adult UK ICHD patients. Findings: Four themes were identified: ‘perceptions of the threat’, ‘impacts on treatment’, ‘impaired communication’ and ‘coping and positive adjustment’. These described participants’ experiences of vulnerability to COVID-19; the ways the pandemic affected dialysis and clinical care; the impact that measures to reduce viral transmission had on communication and interaction within dialysis units; and ways that participants coped and made positive adjustments to the adversities imposed by the pandemic. The findings give insights into adjustment during extreme adversity. They also help to identify ways that support for ICHD patients could be improved as pandemic conditions recede, and ways that dialysis units could prepare for future outbreaks of infectious illness

How to design a complex behaviour change intervention: experiences from a nutrition-sensitive agriculture trial in rural India

Many public health interventions aim to promote healthful behaviours, with varying degrees of success. With a lack of existing empirical evidence on the optimal number or combination of behaviours to promote to achieve a given health outcome, a key challenge in intervention design lies in deciding what behaviours to prioritise, and how best to promote them. We describe how key behaviours were selected and promoted within a multisectoral nutrition-sensitive agriculture intervention that aimed to address maternal and child undernutrition in rural India. First, we formulated a Theory of Change, which outlined our hypothesised impact pathways. To do this, we used the following inputs: existing conceptual frameworks, published empirical evidence, a feasibility study, formative research and the intervention team’s local knowledge. Then, we selected specific behaviours to address within each impact pathway, based on our formative research, behaviour change models, local knowledge and community feedback. As the intervention progressed, we mapped each of the behaviours against our impact pathways and the transtheoretical model of behaviour change, to monitor the balance of behaviours across pathways and along stages of behaviour change. By collectively agreeing on definitions of complex concepts and hypothesised impact pathways, implementing partners were able to communicate clearly between each other and with intervention participants. Our intervention was iteratively informed by continuous review, by monitoring implementation against targets and by integrating community feedback. Impact and process evaluations will reveal whether these approaches are effective for improving maternal and child nutrition, and what the effects are on each hypothesised impact pathway

Molecular correlates of axonal and synaptic pathology in mouse models of Batten disease

Neuronal ceroid lipofuscinoses (NCLs; Batten disease) are collectively the most frequent autosomal-recessive neurodegenerative disease of childhood, but the underlying cellular and molecular mechanisms remain unclear. Several lines of evidence have highlighted the important role that non-somatic compartments of neurons (axons and synapses) play in the instigation and progression of NCL pathogenesis. Here, we report a progressive breakdown of axons and synapses in the brains of two different mouse models of NCL: Ppt1−/− model of infantile NCL and Cln6nclf model of variant late-infantile NCL. Synaptic pathology was evident in the thalamus and cortex of these mice, but occurred much earlier within the thalamus. Quantitative comparisons of expression levels for a subset of proteins previously implicated in regulation of axonal and synaptic vulnerability revealed changes in proteins involved with synaptic function/stability and cell-cycle regulation in both strains of NCL mice. Protein expression changes were present at pre/early-symptomatic stages, occurring in advance of morphologically detectable synaptic or axonal pathology and again displayed regional selectivity, occurring first within the thalamus and only later in the cortex. Although significant differences in individual protein expression profiles existed between the two NCL models studied, 2 of the 15 proteins examined (VDAC1 and Pttg1) displayed robust and significant changes at pre/early-symptomatic time-points in both models. Our study demonstrates that synapses and axons are important early pathological targets in the NCLs and has identified two proteins, VDAC1 and Pttg1, with the potential for use as in vivo biomarkers of pre/early-symptomatic axonal and synaptic vulnerability in the NCLs