Evaluation of proton density fat fraction (PDFF) obtained from a vendor-neutral MRI sequence and MRQuantif software.

OBJECTIVE: To validate the proton density fat fraction (PDFF) obtained by the MRQuantif software from 2D chemical shift encoded MR (CSE-MR) data in comparison with the histological steatosis data. METHODS: This study, pooling data from 3 prospective studies spread over time between January 2007 and July 2020, analyzed 445 patients who underwent 2D CSE-MR and liver biopsy. MR derived liver iron concentration (MR-LIC) and PDFF was calculated using the MRQuantif software. The histological standard steatosis score (SS) served as reference. In order to get a value more comparable to PDFF, histomorphometry fat fraction (HFF) were centrally determined for 281 patients. Spearman correlation and the Bland and Altman method were used for comparison. RESULTS: Strong correlations were found between PDFF and SS (rs = 0.84, p < 0.001) or HFF (rs = 0.87, p < 0.001). Spearman's coefficients increased to 0.88 (n = 324) and 0.94 (n = 202) when selecting only the patients without liver iron overload. The Bland and Altman analysis between PDFF and HFF found a mean bias of 5.4% ± 5.7 [95% CI 4.7, 6.1]. The mean bias was 4.7% ± 3.7 [95% CI 4.2, 5.3] and 7.1% ± 8.8 [95% CI 5.2, 9.0] for the patients without and with liver iron overload, respectively. CONCLUSION: The PDFF obtained by MRQuantif from a 2D CSE-MR sequence is highly correlated with the steatosis score and very close to the fat fraction estimated by histomorphometry. Liver iron overload reduced the performance of steatosis quantification and joint quantification is recommended. This device-independent method can be particularly useful for multicenter studies. CLINICAL RELEVANCE STATEMENT: The quantification of liver steatosis using a vendor-neutral 2D chemical-shift MR sequence, processed by MRQuantif, is well correlated to steatosis score and histomorphometric fat fraction obtained from biopsy, whatever the magnetic field and the MR device used. KEY POINTS: • The PDFF measured by MRQuantif from 2D CSE-MR sequence data is highly correlated to hepatic steatosis. • Steatosis quantification performance is reduced in case of significant hepatic iron overload. • This vendor-neutral method may allow consistent estimation of PDFF in multicenter studies.

Anisotropic mechanical characterization of human skin by in vivo multi-axial ring suction test.

Human skin is a soft tissue behaving as an anisotropic material. The anisotropy emerges from the alignment of collagen fibers in the dermis, which causes the skin to exhibit greater stiffness in a certain direction, known as Langer's line. The importance of determining this anisotropy axis lies in assisting surgeons in making incisions that do not produce undesirable scars. In this paper, we introduce an open-source numerical framework, MARSAC (Multi-Axial Ring Suction for Anisotropy Characterization: https://github.com/aflahelouneg/MARSAC), adapted to a commercial device CutiScan CS 100® that applies a suction load on an annular section, causing a multi-axial stretch in the central zone, where in-plane displacements are captured by a camera. The presented framework receives inputs from a video file and converts them into displacement fields through Digital Image Correlation (DIC) technique. From the latter and based on an analytical model, the method assesses the anisotropic material parameters of human skin: Langer's line ϕ, and the elastic moduli E1 and E2 along the principal axes, providing that the Poisson's ratio is fixed. The pipeline was applied to a public data repository, https://search-data.ubfc.fr/femto/FR-18008901306731-2021-08-25_In-vivo-skin-anisotropy-dataset-for-a-young-man.html, containing 30 test series performed on a forearm of a Caucasian subject. As a result, the identified parameter averages, ϕˆ=40.9±8.2∘ and the anisotropy ratio E1ˆ/E2ˆ=3.14±1.60, were in accordance with the literature. The intra-subject analysis showed a reliable assessment of ϕ and E2. As skin anisotropy varies from site to site and from subject to subject, the novelty of the method consists in (i) an optimal utilization of CutiScan CS 100® probe to measure the Langer's line accurately and rapidly on small areas with a minimum diameter of 14mm, (ii) validation of an analytical model based on deformation ellipticity.

An open source pipeline for design of experiments for hyperelastic models of the skin with applications to keloids.

The aim of this work is to characterize the mechanical parameters governing the in-plane behavior of human skin and, in particular, of a keloid-scar. We consider 2D hyperelastic bi-material model of a keloid and the surrounding healthy skin. The problem of finding the optimal model parameters that minimize the misfit between the model observations and the in vivo experimental measurements is solved using our in-house developed inverse solver that is based on the FEniCS finite element computational platform. The paper focuses on the model parameter sensitivity quantification with respect to the experimental measurements, such as the displacement field and reaction force measurements. The developed tools quantify the significance of different measurements on different model parameters and, in turn, give insight into a given model's ability to capture experimental measurements. Finally, an a priori estimate for the model parameter sensitivity is proposed that is independent of the actual measurements and that is defined in the whole computational domain. This estimate is primarily useful for the design of experiments, specifically, in localizing the optimal displacement field measurement sites for the maximum impact on model parameter inference.

Maternal and neonatal outcomes and prognostic factors in acute fatty liver of pregnancy.

OBJECTIVE: To report complications of Acute Fatty Liver of pregnancy (AFLP), a rare liver disease of pregnancy, and identify prognostic factors for mothers and children. STUDY DESIGN: We conducted a retrospective descriptive study over 18 years in three French maternities. Demographic, clinical, biological data, and outcomes of patients and their infants were reviewed. RESULTS: 142,450 pregnancies from centers were studied. Eighteen patients with AFLP were identified The prevalence of AFLP was estimated as 1/7,914 pregnancies. Prolonged prothrombin time was identified as a risk factor of maternal complications (OR = 0.86, p = 0.0493). Gestational age at delivery was the only risk factor associated with fetal or neonate complications (OR = 0.37, p = 0.0417). One boy died of previously undiagnosed ß-oxidation deficiency at eight months. CONCLUSION: In AFLP, prothrombin time must be carefully monitored to anticipate major maternal complications. Infants born to mothers with ALFP should be screened as early as possible for mitochondrial fatty acid oxidation deficiency.

Conductance switching at the nanoscale of diarylethene derivative self-assembled monolayers on La0.7Sr0.3MnO3.

We report on the phosphonic acid route for the grafting of functional molecules, optical switch (dithienylethene diphosphonic acid, DDA), on La0.7Sr0.3MnO3 (LSMO). Compact self-assembled monolayers (SAMs) of DDA are formed on LSMO as studied by topographic atomic force microscopy (AFM), ellipsometry, water contact angle measurements and X-ray photoemission spectroscopy (XPS). The conducting AFM measurements show that the electrical conductance of LSMO/DDA is about 3 decades below that of a bare LSMO substrate. Moreover, the presence of the DDA SAM suppresses the known conductance switching of the LSMO substrate that is induced by mechanical and/or bias constraints during C-AFM measurements. A partial light-induced conductance switching between the open and closed forms of the DDA is observed for the LSMO/DDA/C-AFM tip molecular junctions (closed/open conductance ratio of about 8). We show that, in the case of long-time exposure to UV light, this feature can be masked by a non-reversible decrease (a factor of about 15) of the conductance of the LSMO electrode.

Dissociation of GaN2+ and AlN2+ in APT: Electronic structure and stability in strong DC field.

We investigate from a theoretical point of view the stability of AlN2+ and GaN2+ dications produced under high static electric fields like those reached in Atom Probe Tomography (APT) experiments. By means of quantum chemical calculations of the electronic structure of these molecules, we show that their stability is governed by two independent processes. On the one hand, the spin-orbit coupling allows some molecular excited states to dissociate by inter-system crossing. On the other hand, the action of the electric field lowers the potential energy barrier, which ensures the dication stability in standard conditions. We present a detailed example of field emission dynamics in the specific case of the 11Δ states for a parabolic tip, which captures the essentials of the process by means of a simplified model. We show that the dissociation dynamics of AlN2+ and GaN2+ is completely different despite the strong resemblance of their electronic structure.

Dissociation of GaN2+ and AlN2+ in APT: Analysis of experimental measurements.

The use of a tip-shaped sample for the atom probe tomography technique offers the unique opportunity to analyze the dynamics of molecular ions in strong DC fields. We investigate here the stability of AlN2+ and GaN2+ dications emitted from an Al0.25Ga0.75N sample in a joint theoretical and experimental study. Despite the strong chemical resemblance of these two molecules, we observe only stable AlN2+, while GaN2+ can only be observed as a transient species. We simulate the emission dynamics of these ions on field-perturbed potential energy surfaces obtained from quantum chemical calculations. We show that the dissociation is governed by two independent processes. For all bound states, a mechanical dissociation is induced by the distortion of the potential energy surface in the close vicinity of the emitting tip. In the specific case of GaN2+, the relatively small electric dipole of the dication in its ground 13Σ- and excited 11Δ states induces a weak coupling with the electric field so that the mechanical dissociation into Ga+ + N+ lasts for sufficient time to be observed. By contrast, the AlN2+ mechanical dissociation leads to Al2+ + N which cannot be observed as a correlated event. For some deeply bound singlet excited states, the spin-orbit coupling with lower energy triplet states gives another chance of dissociation by system inter-system crossing with specific patterns observed experimentally in a correlated time of flight map.

Endocrine therapy or chemotherapy as first-line therapy in hormone receptor-positive HER2-negative metastatic breast cancer patients.

BACKGROUND: For hormone receptor-positive (HR+) human epidermal growth factor receptor 2 (HER2-) negative metastatic breast cancer (MBC), international guidelines recommend endocrine therapy as first-line treatment, except in case of 'visceral crisis'. In the latter case, chemotherapy is preferred. Few studies have compared these two strategies. We used the Epidemiological Strategy and Medical Economics (ESME) programme, UNICANCER, a large national observational database (NCT03275311), to address this question. METHODS: All patients who initiated treatment for a newly diagnosed HR+ HER2-negative MBC between January 2008 and December 2014 in any of the 18 French Comprehensive Cancer Centers participating to ESME were selected. Patients should be aromatase inhibitor (AI)-sensitive (no previous AI or relapse occurring more than 1 year after last adjuvant AI). Objectives of the study were evaluation of progression-free and overall survival (OS) according to the type of first-line treatment adjusted on main prognostic factors using a propensity score. RESULTS: Six thousand two hundred sixty-five patients were selected: 2733 (43.6%) received endocrine therapy alone, while 3532 (56.4%) received chemotherapy as first-line therapy. Among the latter, 2073 (58.7%) received maintenance endocrine therapy. Median OS was 60.78 months (95% confidence interval [CI], 57.16-64.09) and 49.64 months (95% CI, 47.31-51.64; p < 0.0001) for patients receiving endocrine therapy alone and chemotherapy ± maintenance endocrine therapy, respectively. However, this difference was not significant after adjusting on the propensity score (hazard ratio: 0.943, 95% CI 0.863-1.030, p = 0.19). CONCLUSION: In this large retrospective cohort of patients with AI-sensitive metastatic luminal BC, OS was similar, whether first-line treatment was chemotherapy or endocrine therapy. In agreement with international guidelines, endocrine therapy should be the first choice for first-line systemic treatment for MBC in the absence of visceral crisis.

Electronic structure and stability of the SiO2+ dications produced in tomographic atom probe experiments.

The molecular electronic states of the SiO2+ dication have been investigated in a joint theoretical and experimental analysis. The use of a tip-shaped sample for tomographic atom probe analysis offers the unique opportunity to produce and to analyze the lifetime of some excited states of this dication. The perturbation brought by the large electric field of the polarized tip along the ion trajectory is analyzed by means of molecular dynamics simulation. For the typical electric fields used in the experiment, the lowest energy triplet states spontaneously dissociate, while the lowest energy singlet states do not. We show that the emission process leads to the formation of some excited singlet state, which dissociates by means of spin-orbit coupling with lower-energy triplet states to produce specific patterns associated with Si+ + O+ and Si2+ + O dissociation channels. These patterns are recorded and observed experimentally in a correlated time-of-flight map.

Role of a Neighbor Ion in the Fragmentation Dynamics of Covalent Molecules.

Fragmentation of molecular nitrogen dimers (N_{2})_{2} induced by collision with low energy 90 keV Ar^{9+} ions is studied to evidence the influence of a molecular environment on the fragmentation dynamics of N_{2} cations. Following the capture of three or four electrons from the dimer, the three-body N_{2}^{+}+N^{m+}+N^{n+} [with (m,n)=(1,1) or (1, 2)] fragmentation channels provide clean experimental cases where molecular fragmentation may occur in the presence of a neighbor molecular cation. The effect of the environment on the fragmentation dynamics within the dimer is investigated through the comparison of the kinetic energy release (KER) spectra for these three-body channels and for isolated N_{2}^{(m+n)+} monomer cations. The corresponding KER spectra exhibit energy shifts of the order of 10 eV, attributed to the deformation of the N^{m+}+N^{n+} potential energy curves in the presence of the neighboring N_{2}^{+} cation. The KER structures remain unchanged, indicating that the primary collision process is not significantly affected by the presence of a neighbor molecule.

Intra- and inter-individual variability in the mechanical properties of the human skin from in vivo measurements on 20 volunteers.

BACKGROUND/PURPOSE: The mechanical properties and behavior of the human skin in vivo are of medical importance, particularly to surgeons who have to consider the skin extension capabilities in the preparation of surgical acts. Variable data can be found in literature that result from diverse kinds of tests (in vivo, ex vivo, and postmortem) performed with different instruments. METHODS: This paper presents the results of in vivo measurements performed on a cohort of 20 healthy volunteers with an ultralight homemade uniaxial extensometer. Different anatomical zones were explored under different directions of solicitation in order to document inter- and intra-individual variability as well as skin anisotropy. RESULTS: The experimental data obtained are fitted with a phenomenological exponential model allowing the identification of three parameters characteristic of the tested skin behavior. These parameters can be related to the concept of skin extensibility used by surgeons. CONCLUSION: The inter- and intra-variability observed on that cohort confirms the need for a patient-specific approach based on the in vivo measurement of the mechanical behavior of the human skin of interest. Even the direction of higher skin stiffness is found to be individual-dependent. The capability of the extensometer used in this study to fulfill such measurement needs is also demonstrated.

Ultra-light extensometer for the assessment of the mechanical properties of the human skin in vivo.

BACKGROUND/PURPOSE: This paper aims to present an ultra-light extensometer device dedicated to the mechanical characterization of the human skin in vivo. METHODS: The device developed was conceived to be non-invasive, to work without any stand and to perform various uniaxial tensile tests with either effort or displacement control. We also use specific guarding tabs to make in vivo extension tests analogous to traction tests. RESULTS: Force-displacement curves are derived from the data provided by the device's sensors. The latter are converted into stress-strain curves thanks to complementary measurements of the skin thickness. We present typical experimental data and results that demonstrate the device ability to built stress-strain curves characteristic of the human skin behavior. An additional imaging unit records a sequence of images of the solicited skin area for further calculations of the displacement fields by digital image correlation. CONCLUSION: The analysis of the displacement and deformation fields validates the guarding tab efficiency and the capacity of the device to characterize the mechanical behavior of the human skin in vivo.

Assessment of liver iron overload by 3 T MRI.

PURPOSE: To evaluate the performance and limitations of the signal intensity ratio method for quantifying liver iron overload at 3 T. METHODS: Institutional review board approval and written informed consent from all participants were obtained. One hundred and five patients were included prospectively. All patients underwent a liver biopsy with biochemical assessment of hepatic iron concentration and a 3 T MRI scan with 5 breath-hold single-echo gradient-echo sequences. Linear correlation between liver-to-muscle signal intensity ratio and liver iron concentration was calculated. The algorithm for calculating magnetic resonance hepatic iron concentration was adapted from the method described by Gandon et al. with echo times divided by 2. Sensitivity and specificity were calculated. RESULTS: Five patients were excluded (coil selection failure or missing sequence) and 100 patients were analyzed, 64 men and 36 women, 52 ± 13.3 years old, with a biochemical hepatic iron concentration range of 0-630 µmol/g. Linear correlation between biochemical hepatic iron concentration and MR-hepatic iron concentration was excellent with a correlation coefficient = 0.96, p < 0.0001. Sensitivity and specificity were, respectively, 83% (0.70-0.92) and 96% (0.85-0.99), with a pathological threshold of 36 µmol/g. CONCLUSION: Signal intensity ratio method for quantifying liver iron overload can be used at 3 T with echo times divided by 2.

Highly efficient and tunable spin-to-charge conversion through Rashba coupling at oxide interfaces.

The spin-orbit interaction couples the electrons' motion to their spin. As a result, a charge current running through a material with strong spin-orbit coupling generates a transverse spin current (spin Hall effect, SHE) and vice versa (inverse spin Hall effect, ISHE). The emergence of SHE and ISHE as charge-to-spin interconversion mechanisms offers a variety of novel spintronic functionalities and devices, some of which do not require any ferromagnetic material. However, the interconversion efficiency of SHE and ISHE (spin Hall angle) is a bulk property that rarely exceeds ten percent, and does not take advantage of interfacial and low-dimensional effects otherwise ubiquitous in spintronic hetero- and mesostructures. Here, we make use of an interface-driven spin-orbit coupling mechanism-the Rashba effect-in the oxide two-dimensional electron system (2DES) LaAlO3/SrTiO3 to achieve spin-to-charge conversion with unprecedented efficiency. Through spin pumping, we inject a spin current from a NiFe film into the oxide 2DES and detect the resulting charge current, which can be strongly modulated by a gate voltage. We discuss the amplitude of the effect and its gate dependence on the basis of the electronic structure of the 2DES and highlight the importance of a long scattering time to achieve efficient spin-to-charge interconversion.

Long-Term Survivor with Intrathecal and Intravenous Trastuzumab Treatment in Metastatic Breast Cancer.

We report the case of a woman with metastatic breast cancer receiving intrathecal trastuzumab (and intravenous trastuzumab for more than 7 years). She was diagnosed in 2001 with a duct invasive breast cancer T3N1M0 HER2 (human epidermal growth factor receptor 2)-positive +++ HR (hormone receptor) -negative. She received chemotherapy and then she had a mastectomy. Several metastases were discovered and treated from 2003 to 2008 with chemotherapy. In March 2010, brain metastases and a leptomeningeal carcinomatosis from her HER2-positive breast cancer appeared. From that moment on she received intravenous trastuzumab (6 mg/kg) every 3 weeks, intrathecal trastuzumab (21 mg) weekly for 16 injections and lapatinib. Intrathecal trastuzumab was stopped because of cerebrospinal fluid (CSF) clearing. Intrathecal trastuzumab was injected again from December 2013 for 14 injections. The relevance of treating leptomeningeal carcinomatosis with intrathecal trastuzumab administration is shown through this case report.

Numerical analysis of the V-Y shaped advancement flap.

The V-Y advancement flap is a usual technique for the closure of skin defects. A triangular flap is incised adjacent to a skin defect of rectangular shape. As the flap is advanced to close the initial defect, two smaller defects in the shape of a parallelogram are formed with respect to a reflection symmetry. The height of the defects depends on the apex angle of the flap and the closure efforts are related to the defects height. Andrades et al. 2005 have performed a geometrical analysis of the V-Y flap technique in order to reach a compromise between the flap size and the defects width. However, the geometrical approach does not consider the mechanical properties of the skin. The present analysis based on the finite element method is proposed as a complement to the geometrical one. This analysis aims to highlight the major role of the skin elasticity for a full analysis of the V-Y advancement flap. Furthermore, the study of this technique shows that closing at the flap apex seems mechanically the most interesting step. Thus different strategies of defect closure at the flap apex stemming from surgeon's know-how have been tested by numerical simulations.

Local electrical control of magnetic order and orientation by ferroelastic domain arrangements just above room temperature.

Ferroic materials (ferromagnetic, ferroelectric, ferroelastic) usually divide into domains with different orientations of their order parameter. Coupling between different ferroic systems creates new functionalities, for instance the electrical control of macroscopic magnetic properties including magnetization and coercive field. Here we show that ferroelastic domains can be used to control both magnetic order and magnetization direction at the nanoscale with a voltage. We use element-specific X-ray imaging to map the magnetic domains as a function of temperature and voltage in epitaxial FeRh on ferroelastic BaTiO3. Exploiting the nanoscale phase-separation of FeRh, we locally interconvert between ferromagnetic and antiferromagnetic states with a small electric field just above room temperature. Imaging and ab initio calculations show the antiferromagnetic phase of FeRh is favoured by compressive strain on c-oriented BaTiO3 domains, and the resultant magnetoelectric coupling is larger and more reversible than previously reported from macroscopic measurements. Our results emphasize the importance of nanoscale ferroic domain structure and the promise of first-order transition materials to achieve enhanced coupling in artificial multiferroics.

Control of ferroelectricity and magnetism in multi-ferroic BiFeO3 by epitaxial strain.

Recently, strain engineering has been shown to be a powerful and flexible means of tailoring the properties of ABO3 perovskite thin films. The effect of epitaxial strain on the structure of the perovskite unit cell can induce a host of interesting effects, these arising from either polar cation shifts or rotation of the oxygen octahedra, or both. In the multi-ferroic perovskite bismuth ferrite (BiFeO3-BFO), both degrees of freedom exist, and thus a complex behaviour may be expected as one plays with epitaxial strain. In this paper, we review our results on the role of strain on the ferroic transition temperatures and ferroic order parameters. We find that, while the Néel temperature is almost unchanged by strain, the ferroelectric Curie temperature strongly decreases as strain increases in both the tensile and compressive ranges. Also unexpected is the very weak influence of strain on the ferroelectric polarization value. Using effective Hamiltonian calculations, we show that these peculiar behaviours arise from the competition between antiferrodistortive and polar instabilities. Finally, we present results on the magnetic order: while the cycloidal spin modulation present in the bulk survives in weakly strained films, it is destroyed at large strain and replaced by pseudo-collinear antiferromagnetic ordering. We discuss the origin of this effect and give perspectives for devices based on strain-engineered BiFeO3.

Electric-field control of magnetic order above room temperature.

Controlling magnetism by means of electric fields is a key issue for the future development of low-power spintronics. Progress has been made in the electrical control of magnetic anisotropy, domain structure, spin polarization or critical temperatures. However, the ability to turn on and off robust ferromagnetism at room temperature and above has remained elusive. Here we use ferroelectricity in BaTiO3 crystals to tune the sharp metamagnetic transition temperature of epitaxially grown FeRh films and electrically drive a transition between antiferromagnetic and ferromagnetic order with only a few volts, just above room temperature. The detailed analysis of the data in the light of first-principles calculations indicate that the phenomenon is mediated by both strain and field effects from the BaTiO3. Our results correspond to a magnetoelectric coupling larger than previous reports by at least one order of magnitude and open new perspectives for the use of ferroelectrics in magnetic storage and spintronics.