Spider Bite Presenting as Fever, Macrophage Activation Syndrome and a Skin Ulcer.

Introduction: Fever of unknown origin (FUO) refers to a condition of prolonged increased body temperature, without identified causes. The most common cause of FUO worldwide are infections; arthropod bites (loxoscelism) should be considered in view of the spread of the fiddleback spider. Loxoscelism can present in a cutaneous form (a necrotic cutaneous ulcer) or in a systemic form with fever, haemolytic anaemia, rhabdomyolysis and, rarely, macrophage activation syndrome (MAS). For this suspicion, it is important to have actually seen the spider. Case description: A 71-year-old man was admitted to our department because of intermittent fever, arthralgia and a necrotic skin lesion on his right forearm that appeared after gardening. Laboratory tests were negative for infectious diseases, and several courses of antibiotics were administered empirically without clinical benefit. Whole-body computed tomography showed multiple colliquative lymphadenomegalies, the largest one in the right axilla, presumably of reactive significance. A shave biopsy of the necrotic lesion was performed: culture tests were negative and histological examination showed non-specific necrotic material, so a second skin and lymph node biopsy was performed. The patient developed MAS for which he received corticosteroid therapy with clinical/laboratory benefit. Cutaneous and systemic loxoscelism complicated by MAS was diagnosed. Subsequently, the second biopsy revealed morphological and immunophenotypic findings consistent with primary cutaneous anaplastic large cell lymphoma (PC-ALCL). Conclusions: Skin lesions and lymphadenomegalies of unknown origin should always be biopsied. It is very common to get indeterminate results, but this does not justify not repeating the procedure to avoid misdiagnosis. LEARNING POINTS: In case of necrotic skin lesions with fever, malignancy (and in particular cutaneous lymphoma) should always be considered.Misdiagnosis of loxoscelism is common. Definitive diagnosis requires the identification of the responsible spider.It is frequent to obtain inconclusive results from biopsies, but this does not justify not repeating the procedure to avoid misdiagnosis.

lifex-ep: a robust and efficient software for cardiac electrophysiology simulations.

BACKGROUND: Simulating the cardiac function requires the numerical solution of multi-physics and multi-scale mathematical models. This underscores the need for streamlined, accurate, and high-performance computational tools. Despite the dedicated endeavors of various research teams, comprehensive and user-friendly software programs for cardiac simulations, capable of accurately replicating both normal and pathological conditions, are still in the process of achieving full maturity within the scientific community. RESULTS: This work introduces [Formula: see text]-ep, a publicly available software for numerical simulations of the electrophysiology activity of the cardiac muscle, under both normal and pathological conditions. [Formula: see text]-ep employs the monodomain equation to model the heart's electrical activity. It incorporates both phenomenological and second-generation ionic models. These models are discretized using the Finite Element method on tetrahedral or hexahedral meshes. Additionally, [Formula: see text]-ep integrates the generation of myocardial fibers based on Laplace-Dirichlet Rule-Based Methods, previously released in Africa et al., 2023, within [Formula: see text]-fiber. As an alternative, users can also choose to import myofibers from a file. This paper provides a concise overview of the mathematical models and numerical methods underlying [Formula: see text]-ep, along with comprehensive implementation details and instructions for users. [Formula: see text]-ep features exceptional parallel speedup, scaling efficiently when using up to thousands of cores, and its implementation has been verified against an established benchmark problem for computational electrophysiology. We showcase the key features of [Formula: see text]-ep through various idealized and realistic simulations conducted in both normal and pathological scenarios. Furthermore, the software offers a user-friendly and flexible interface, simplifying the setup of simulations using self-documenting parameter files. CONCLUSIONS: [Formula: see text]-ep provides easy access to cardiac electrophysiology simulations for a wide user community. It offers a computational tool that integrates models and accurate methods for simulating cardiac electrophysiology within a high-performance framework, while maintaining a user-friendly interface. [Formula: see text]-ep represents a valuable tool for conducting in silico patient-specific simulations.

lifex-fiber: an open tool for myofibers generation in cardiac computational models.

BACKGROUND: Modeling the whole cardiac function involves the solution of several complex multi-physics and multi-scale models that are highly computationally demanding, which call for simpler yet accurate, high-performance computational tools. Despite the efforts made by several research groups, no software for whole-heart fully-coupled cardiac simulations in the scientific community has reached full maturity yet. RESULTS: In this work we present [Formula: see text]-fiber, an innovative tool for the generation of myocardial fibers based on Laplace-Dirichlet Rule-Based Methods, which are the essential building blocks for modeling the electrophysiological, mechanical and electromechanical cardiac function, from single-chamber to whole-heart simulations. [Formula: see text]-fiber is the first publicly released module for cardiac simulations based on [Formula: see text], an open-source, high-performance Finite Element solver for multi-physics, multi-scale and multi-domain problems developed in the framework of the iHEART project, which aims at making in silico experiments easily reproducible and accessible to a wide community of users, including those with a background in medicine or bio-engineering. CONCLUSIONS: The tool presented in this document is intended to provide the scientific community with a computational tool that incorporates general state of the art models and solvers for simulating the cardiac function within a high-performance framework that exposes a user- and developer-friendly interface. This report comes with an extensive technical and mathematical documentation to welcome new users to the core structure of [Formula: see text]-fiber and to provide them with a possible approach to include the generated cardiac fibers into more sophisticated computational pipelines. In the near future, more modules will be successively published either as pre-compiled binaries for x86-64 Linux systems or as open source software.

Simple and statistically sound recommendations for analysing physical theories.

Physical theories that depend on many parameters or are tested against data from many different experiments pose unique challenges to statistical inference. Many models in particle physics, astrophysics and cosmology fall into one or both of these categories. These issues are often sidestepped with statistically unsound ad hoc methods, involving intersection of parameter intervals estimated by multiple experiments, and random or grid sampling of model parameters. Whilst these methods are easy to apply, they exhibit pathologies even in low-dimensional parameter spaces, and quickly become problematic to use and interpret in higher dimensions. In this article we give clear guidance for going beyond these procedures, suggesting where possible simple methods for performing statistically sound inference, and recommendations of readily-available software tools and standards that can assist in doing so. Our aim is to provide any physicists lacking comprehensive statistical training with recommendations for reaching correct scientific conclusions, with only a modest increase in analysis burden. Our examples can be reproduced with the code publicly available at Zenodo.

Electromechanical modeling of human ventricles with ischemic cardiomyopathy: numerical simulations in sinus rhythm and under arrhythmia.

We developed a novel patient-specific computational model for the numerical simulation of ventricular electromechanics in patients with ischemic cardiomyopathy (ICM). This model reproduces the activity both in sinus rhythm (SR) and in ventricular tachycardia (VT). The presence of scars, grey zones and non-remodeled regions of the myocardium is accounted for by the introduction of a spatially heterogeneous coefficient in the 3D electromechanics model. This 3D electromechanics model is firstly coupled with a 2-element Windkessel afterload model to fit the pressure-volume (PV) loop of a patient-specific left ventricle (LV) with ICM in SR. Then, we employ the coupling with a 0D closed-loop circulation model to analyze a VT circuit over multiple heartbeats on the same LV. We highlight similarities and differences on the solutions obtained by the electrophysiology model and those of the electromechanics model, while considering different scenarios for the circulatory system. We observe that very different parametrizations of the circulation model induce the same hemodynamical considerations for the patient at hand. Specifically, we classify this VT as unstable. We conclude by stressing the importance of combining electrophysiological, mechanical and hemodynamical models to provide relevant clinical indicators in how arrhythmias evolve and can potentially lead to sudden cardiac death.

Muon g-2 and B Anomalies from Dark Matter.

In light of the recent result of the muon g-2 experiment and the update on the test of lepton flavor universality R_{K} published by the LHCb Collaboration, we systematically study for the first time a set of models with minimal field content that can simultaneously give (i) a thermal dark matter candidate; (ii) large loop contributions to b→sℓℓ processes able to address R_{K} and the other B anomalies; (iii) a natural solution to the muon g-2 discrepancy through chirally enhanced contributions. Moreover, this type of model with heavy particles and chiral enhancement can evade the strong limits from direct searches but can be tested at present and future colliders and direct-detection searches.

Polygonal surface processing and mesh generation tools for the numerical simulation of the cardiac function.

In order to simulate the cardiac function for a patient-specific geometry, the generation of the computational mesh is crucially important. In practice, the input is typically a set of unprocessed polygonal surfaces coming either from a template geometry or from medical images. These surfaces need ad-hoc processing to be suitable for a volumetric mesh generation. In this work we propose a set of new algorithms and tools aiming to facilitate the mesh generation process. In particular, we focus on different aspects of a cardiac mesh generation pipeline: (1) specific polygonal surface processing for cardiac geometries, like connection of different heart chambers or segmentation outputs; (2) generation of accurate boundary tags; (3) definition of mesh-size functions dependent on relevant geometric quantities; (4) processing and connecting together several volumetric meshes. The new algorithms-implemented in the open-source software vmtk-can be combined with each other allowing the creation of personalized pipelines, that can be optimized for each cardiac geometry or for each aspect of the cardiac function to be modeled. Thanks to these features, the proposed tools can significantly speed-up the mesh generation process for a large range of cardiac applications, from single-chamber single-physics simulations to multi-chambers multi-physics simulations. We detail all the proposed algorithms motivating them in the cardiac context and we highlight their flexibility by showing different examples of cardiac mesh generation pipelines.

Image-Based Computational Hemodynamics Analysis of Systolic Obstruction in Hypertrophic Cardiomyopathy.

Hypertrophic Cardiomyopathy (HCM) is a pathological condition characterized by an abnormal thickening of the myocardium. When affecting the medio-basal portion of the septum, it is named Hypertrophic Obstructive Cardiomyopathy (HOCM) because it induces a flow obstruction in the left ventricular outflow tract. In any type of HCM, the myocardial function can become compromised, possibly resulting in cardiac death. In this study, we investigated with computational analysis the hemodynamics of patients with different types of HCM. The aim was quantifying the effects of this pathology on the intraventricular blood flow and pressure gradients, and providing information potentially useful to guide the indication and the modality of the surgical treatment (septal myectomy). We employed an image-based computational approach, integrating fluid dynamics simulations with geometric and functional data, reconstructed from standard cardiac cine-MRI acquisitions. We showed that with our approach we can better understand the patho-physiological behavior of intraventricular blood flow dynamics due to the abnormal morphological and functional aspect of the left ventricle. The main results of our investigation are: (a) a detailed patient-specific analysis of the blood velocity, pressure and stress distribution associated to HCM; (b) a computation-based classification of patients affected by HCM that can complement the current clinical guidelines for the diagnosis and treatment of HOCM.

Solar Axions Cannot Explain the XENON1T Excess.

We argue that the interpretation in terms of solar axions of the recent XENON1T excess is not tenable when confronted with astrophysical observations of stellar evolution. We discuss the reasons why the emission of a flux of solar axions sufficiently intense to explain the anomalous data would radically alter the distribution of certain type of stars in the color-magnitude diagram in the first place and would also clash with a certain number of other astrophysical observables. Quantitatively, the significance of the discrepancy ranges from 3.3σ for the rate of period change of pulsating white dwarfs and exceeds 19σ for the R parameter and for M_{I,TRGB}.

An image-based computational hemodynamics study of the Systolic Anterior Motion of the mitral valve.

Systolic Anterior Motion (SAM) of the mitral valve - often associated with Hypertrophic Obstructive Cardiomyopathy (HOCM) - is a cardiac pathology in which a functional subaortic stenosis is induced during systole by the mitral leaflets partially obstructing the outflow tract of the left ventricle. Its assessment by diagnostic tests is often difficult, possibly underestimating its severity and thus increasing the risk of heart failure. In this paper, we propose a new computational pipeline, based on cardiac cine Magnetic Resonance Imaging (cine-MRI) data, for the assessment of SAM. The pipeline encompasses image processing of the left ventricle and the mitral valve, and numerical investigation of cardiac hemodynamics by means of Computational Fluid Dynamics (CFD) in a moving domain with image-based prescribed displacement. Patient-specific geometry and motion of the left ventricle are considered in view of an Arbitrary Lagrangian-Eulerian approach for CFD, while the reconstructed mitral valve is immersed in the computational domain by means of a resistive method. We assess clinically relevant flow and pressure indicators in a parametric study for different degrees of SAM severity, in order to provide a better quantitative evaluation of the pathological condition. Moreover, we provide specific indications for its possible surgical treatment, i.e. septal myectomy.

The Impact of Left Atrium Appendage Morphology on Stroke Risk Assessment in Atrial Fibrillation: A Computational Fluid Dynamics Study.

Atrial fibrillation (AF) carries out a 5-fold increase in stroke risk, related to embolization of thrombi clotting in left atrium (LA). Left atrial appendage (LAA) is the site with the highest blood stasis which causes thrombus formation. About 90 % of the intracardiac thrombi in patients with cardioembolic events originally develop in the LAA. Recent studies have been focused on the association between LAA anatomical features and stroke risk and provided conflicting results. Haemodynamic and fluid dynamic information on the LA and mostly on the LAA may improve stroke risk stratification. Therefore, the aim of this study was the design and development of a workflow to quantitatively define the influence of the LAA morphology on LA hemodynamics. Five 3D LA anatomical models, obtained from real clinical data, which were clearly different as regard to LAA morphology were used. For each LAA we identified and computed several parameters describing its geometry. Then, one LA chamber model was chosen and a framework was developed to connect the different LAAs belonging to the other four patients to this model. These new anatomical models represented the computational domain for the computational fluid dynamics (CFD) study; simulations of the hemodynamics within the LA and LAA were performed in order to evaluate the interplay of the LAA shape on the blood flow characteristics in AF condition. CFD simulations were carried out for five cardiac cycles. Blood velocity, vorticity, LAA orifice velocity, residence time computed in the five models were compared and correlated with LAA morphologies. Results showed that not only complex morphologies were characterized by low velocities, low vorticity and consequently could carry a higher thrombogenic risk; even qualitatively simple morphologies showed a thrombogenic risk equal, or even higher, than more complex auricles. CFD results supported the hypothesis that LAA geometric characteristics plays a key-role in defining thromboembolic risk. LAA geometric parameters could be considered, coupled with the morphological characteristics, for a comprehensive evaluation of the regional blood stasis. The proposed procedure might address the development of a tool for patient-specific stroke risk assessment and preventive treatment in AF patients, relying on morpho-functional defintion of each LAA type.

A patient-specific aortic valve model based on moving resistive immersed implicit surfaces.

In this paper, we propose a full computational framework to simulate the hemodynamics in the aorta including the valve. Closed and open valve surfaces, as well as the lumen aorta, are reconstructed directly from medical images using new ad hoc algorithms, allowing a patient-specific simulation. The fluid dynamics problem that accounts from the movement of the valve is solved by a new 3D-0D fluid-structure interaction model in which the valve surface is implicitly represented through level set functions, yielding, in the Navier-Stokes equations, a resistive penalization term enforcing the blood to adhere to the valve leaflets. The dynamics of the valve between its closed and open position is modeled using a reduced geometric 0D model. At the discrete level, a finite element formulation is used and the SUPG stabilization is extended to include the resistive term in the Navier-Stokes equations. Then, after time discretization, the 3D fluid and 0D valve models are coupled through a staggered approach. This computational framework, applied to a patient-specific geometry and data, allows to simulate the movement of the valve, the sharp pressure jump occurring across the leaflets, and the blood flow pattern inside the aorta.

On flavourful Easter eggs for New Physics hunger and lepton flavour universality violation.

Within the standard approach of effective field theory of weak interactions for Δ B = 1 transitions, we look for possibly unexpected subtle New Physics effects, here dubbed "flavourful Easter eggs". We perform a Bayesian global fit using the publicly available HEPfit package, taking into account state-of-the-art experimental information concerning these processes, including the suggestive measurements from LHCb of R K and R K ∗ , the latter available only very recently. We parametrise New Physics contributions to b → s transitions in terms of shifts of Wilson coefficients of the electromagnetic dipole and semileptonic operators, assuming CP-conserving effects, but allowing in general for violation of lepton flavour universality. We show how optimistic/conservative hadronic estimates can impact quantitatively the size of New Physics extracted from the fit. With a conservative approach to hadronic uncertainties we find nonzero New Physics contributions to Wilson coefficients at the level of ∼ 3 σ , depending on the model chosen. Furthermore, given the interplay between hadronic contributions and New Physics effects in the leptonic vector current, a scenario with nonstandard leptonic axial currents is comparable to the more widely advocated one with New Physics in the leptonic vector current.

Fractional flow reserve based on computed tomography: an overview.

Computed tomography coronary angiography (CTCA) is a technique proved to provide high sensitivity and negative predictive value for the identification of anatomically significant coronary artery disease (CAD) when compared with invasive X-ray coronary angiography. While the CTCA limitation of a ionizing radiation dose delivered to patients is substantially overcome by recent technical innovations, a relevant limitation remains the only anatomical assessment of coronary stenoses in the absence of evaluation of their functional haemodynamic significance. This limitation is highly important for those stenosis graded as intermediate at the anatomical assessment. Recently, non-invasive methods based on computational fluid dynamics were developed to calculate vessel-specific fractional flow reserve (FFR) using data routinely acquired by CTCA [computed tomographic fractional flow reserve (CT-FFR)]. Here we summarize methods for CT-FFR and review the evidence available in the literature up to June 26, 2016, including 16 original articles and one meta-analysis. The perspective of CT-FFR may greatly impact on CAD diagnosis, prognostic evaluation, and treatment decision-making. The aim of this review is to describe technical characteristics and clinical applications of CT-FFR, also in comparison with catheter-based invasive FFR, in order to make a cost-benefit balance in terms of clinical management and patient's health.