Physiology and coronary artery disease: emerging insights from computed tomography imaging based computational modeling

Improvements in spatial and temporal resolution now permit robust high quality characterization of presence, morphology and composition of coronary atherosclerosis in computed tomography (CT). These characteristics include high risk features such as large plaque volume, low CT attenuation, napkin-ring sign, spotty calcification and positive remodeling. Because of the high image quality, principles of patient-specific computational fluid dynamics modeling of blood flow through the coronary arteries can now be applied to CT and allow the calculation of local lesion-specific hemodynamics such as endothelial shear stress, fractional flow reserve and axial plaque stress. This review examines recent advances in coronary CT image-based computational modeling and discusses the opportunity to identify lesions at risk for rupture much earlier than today through the combination of anatomic and hemodynamic information

A Prediction Model to Prioritize Individuals for a SARS-CoV-2 Test Built from National Symptom Surveys

Background: The gold standard for COVID-19 diagnosis is detection of viral RNA through PCR. Due to global limitations in testing capacity, effective prioritization of individuals for testing is essential. Methods: We devised a model estimating the probability of an individual to test positive for COVID-19 based on answers to 9 simple questions that have been associated with SARS-CoV-2 infection. Our model was devised from a subsample of a national symptom survey that was answered over 2 million times in Israel in its first 2 months and a targeted survey distributed to all residents of several cities in Israel. Overall, 43,752 adults were included, from which 498 self-reported as being COVID-19 positive. Findings: Our model was validated on a held-out set of individuals from Israel where it achieved an auROC of 0.737 (CI: 0.712–0.759) and auPR of 0.144 (CI: 0.119–0.177) and demonstrated its applicability outside of Israel in an independently collected symptom survey dataset from the US, UK, and Sweden. Our analyses revealed interactions between several symptoms and age, suggesting variation in the clinical manifestation of the disease in different age groups. Conclusions: Our tool can be used online and without exposure to suspected patients, thus suggesting worldwide utility in combating COVID-19 by better directing the limited testing resources through prioritization of individuals for testing, thereby increasing the rate at which positive individuals can be identified. Moreover, individuals at high risk for a positive test result can be isolated prior to testing. Funding: E.S. is supported by the Crown Human Genome Center, Larson Charitable Foundation New Scientist Fund, Else Kroener Fresenius Foundation, White Rose International Foundation, Ben B. and Joyce E. Eisenberg Foundation, Nissenbaum Family, Marcos Pinheiro de Andrade and Vanessa Buchheim, Lady Michelle Michels, and Aliza Moussaieff and grants funded by the Minerva foundation with funding from the Federal German Ministry for Education and Research and by the European Research Council and the Israel Science Foundation. H.R. is supported by the Israeli Council for Higher Education (CHE) via the Weizmann Data Science Research Center and by a research grant from Madame Olga Klein – Astrachan

Pilot study of the multicentre DISCHARGE trial: image quality and protocol adherence results of computed tomography and invasive coronary angiography (vol 30, pg 1997, 2020)

The original version of this article, published on 16 December 2019, unfortunately contained two mistakes.Cardiovascular Aspects of Radiolog

Constructing narratives and reading texts: Approaches to history and power struggles between philosophy and emergent disciplines in inter-war France

In inter-war France, history of philosophy was a very important academic discipline, but nevertheless its practitioners thought it necessary to defend its identity, which was threatened by its vicinity to many other disciplines, and especially by the emergent social sciences and history of science. I shall focus on two particular issues that divided traditional historians of philosophy from historians of science, ethnologists and sociologists, and that became crucial in the definition of the identity of their disciplines: the conception of history and the interpretation of texts. By analysing representative discussions and positions, I shall show that traditional historians of philosophy needed to reassert their own approach to history, which, borrowing the term from Bergson, I define as ‘snapshot’. This approach is focused on a particular idea or text rather than a narrative. I shall also show that history of philosophy, in its traditional form, would have been undermined both intellectually and institutionally by the opposite ‘narrative’ approach of history of science and of the social sciences. Social scientists openly attacked history of philosophy’s methods and, in the eyes of traditional philosophers, its existence as an academic discipline. The same opposition is to be found in evaluation of past texts, which for traditional historians of philosophy were to be read as timeless documents, while for historians of science, ethnologists and sociologists were to be considered as documents exhibiting a particular mentality. However, between these alternatives there were intermediate positions. I shall in particular consider that of Léon Brunschvicg: he embraced a narrative approach and considered texts as documents of different ways of thinking, but at the same time carried on employing philosophical methods and defending the institutional position of philosophy. I shall argue that this was possible partly because of the considerable amount of power he enjoyed at the Sorbonne

Cell-surface receptors enable perception of extracellular cytokinins

Cytokinins are mobile multifunctional plant hormones with roles in development and stress resilience. Although their Histidine Kinase receptors are substantially localised to the endoplasmic reticulum, cellular sites of cytokinin perception and importance of spatially heterogeneous cytokinin distribution continue to be debated. Here we show that cytokinin perception by plasma membrane receptors is an effective additional path for cytokinin response. Readout from a Two Component Signalling cytokinin-specific reporter (TCSn::GFP) closely matches intracellular cytokinin content in roots, yet we also find cytokinins in extracellular fluid, potentially enabling action at the cell surface. Cytokinins covalently linked to beads that could not pass the plasma membrane increased expression of both TCSn::GFP and Cytokinin Response Factors. Super-resolution microscopy of GFP-labelled receptors and diminished TCSn::GFP response to immobilised cytokinins in cytokinin receptor mutants, further indicate that receptors can function at the cell surface. We argue that dual intracellular and surface locations may augment flexibility of cytokinin responses. The main site of cytokinin perception in plant cells is thought to be the endoplasmic reticulum where most cytokinin receptors localise. Here via the use of bioactive probes that cannot enter plant cells and super-resolution microscopy, Antoniadi et al. show that cytokinin can also be perceived at the plasma membrane

The mind and the faculties: the controversy over 'primitive mentality' and the struggle for disciplinary space at the interwar Sorbonne

This article deals with some aspects of the study of the mind between the 1920s and 1940s at the University of Paris. Traditionally the domain of philosophy, the study of the mind was encroached upon by other disciplines such as history of science, ethnology, sociology and psychology. These disciplines all had weak institutional status and were struggling to constitute themselves as autonomous. History of science did not as a rule reject its relationship with philosophy, whereas ethnology, sociology and psychology were constructing their identities by breaking away from philosophy. A discussion about Lévy-Bruhl’s La mentalité primitive, hosted by the Société Française de Philosophie in 1923, showed that the positions of philosophers, sociologists and psychologists about the questions posed by the book, namely the fixity and universality of the mind, were strictly linked with their views about the ‘scientificity’ of ethnology. A compromise between fixity and historical transformation of the mind was put forward by Gaston Bachelard, who institutionally represented the discipline of history and philosophy of science. This discipline was institutionally linked to ethnology, psychology and sociology, but, unlike them, had no claim to ‘scientificity’. Bachelard realized this compromise by breaking the unity of the mind and by employing an extra-institutional discipline: psychoanalysis. His freedom of choice corresponded with an increasingly weak institutional position for the discipline of history and philosophy of science

Validation of Wall Shear Stress Assessment in Non-invasive Coronary CTA versus Invasive Imaging: A Patient-Specific Computational Study

Endothelial shear stress (ESS) identifies coronary plaques at high risk for progression and/or rupture leading to a future acute coronary syndrome. In this study an optimized methodology was developed to derive ESS, pressure drop and oscillatory shear index using computational fluid dynamics (CFD) in 3D models of coronary arteries derived from non-invasive coronary computed tomography angiography (CTA). These CTA-based ESS calculations were compared to the ESS calculations using the gold standard with fusion of invasive imaging and CTA. In 14 patients paired patient-specific CFD models based on invasive and non-invasive imaging of the left anterior descending (LAD) coronary arteries were created. Ten patients were used to optimize the methodology, and four patients to test this methodology. Time-averaged ESS (TAESS) was calculated for both coronary models applying patient-specific physiological data available at the time of imaging. For data analysis, each 3D reconstructed coronary artery was divided into 2 mm segments and each segment was subdivided into 8 arcs (45°).TAESS and other hemodynamic parameters were averaged per segment as well as per arc. Furthermore, the paired segment- and arc-averaged TAESS were categorized into patient-specific tertiles (low, medium and high). In the ten LADs, used for optimization of the methodology, we found high correlations between invasively-derived and non-invasively-derived TAESS averaged over segments (n = 263, r = 0.86) as well as arcs (n = 2104, r = 0.85, p < 0.001). The correlation was also strong in the four testing-patients with r = 0.95 (n = 117 segments, p = 0.001) and r = 0.93 (n = 936 arcs, p = 0.001).There was an overall high concordance of 78% of the three TAESS categories comparing both methodologies using the segment- and 76% for the arc-averages in the first ten patients. This concordance was lower in the four testing patients (64 and 64% in segment- and arc-averaged TAESS). Although the correlation and concordance were high for both patient groups, the absolute TAESS values averaged per segment and arc were overestimated using non-invasive vs. invasive imaging [testing patients: TAESS segment: 30.1(17.1–83.8) vs. 15.8(8.8–63.4) and TAESS arc: 29.4(16.2–74.7) vs 15.0(8.9–57.4) p < 0.001]. We showed that our methodology can accurately assess the TAESS distribution non-invasively from CTA and demonstrated a good correlation with TAESS calculated using IVUS/OCT 3D reconstructed models