Quantum motion of oxygen and hydrogen in water: Atomic and total kinetic energy across melting from neutron scattering measurements.

We provide a concurrent measurement of the hydrogen and oxygen nuclear kinetic energies in the water molecule across melting at 270 K in the solid phase and 276 K in the liquid phase. Experimental values are obtained by analyzing the neutron Compton profiles of each atomic species in a deep inelastic neutron scattering experiment. The concurrent measurement of the atom kinetic energy of both hydrogen and oxygen allows the estimate of the total kinetic energy per molecule due to the motion of nuclei, specifically 35.3 ± 0.8 and 34.8 ± 0.8 kJ/mol for the solid and liquid phases, respectively. Such a small difference supports results from ab initio simulations and phenomenological models from the literature on the mechanism of competing quantum effects across the phase change. Despite the experimental uncertainties, the results are consistent with the trend from state-of-the-art computer simulations, whereby the atom and molecule kinetic energies in the liquid phase would be slightly lower than in the solid phase. Moreover, the small change of nuclear kinetic energy across melting can be used to simplify the calculation of neutron-related environmental dose in complex locations, such as high altitude or polar neutron radiation research stations where liquid water and ice are both present: for neutron energies between hundreds of meV and tens of keV, the total scattering cross section per molecule in the two phases can be considered the same, with the macroscopic cross section only depending upon the density changes of water near the melting point.

Prognostic value of exercise longitudinal right ventricular free wall strain in patients with sickle cell disease.

Longitudinal right ventricular free wall strain (RVFWS) has been identified as an independent prognostic marker in patients with pulmonary hypertension. Little is known however about the prognostic value of RVFWS in patients with sickle cell (SC) disease, particularly during exercise. We therefore examined the prognostic significance of RVFWS both at rest and with exercise in patients with SC disease and normal resting systolic pulmonary artery pressure (SPAP). Consecutive patients with SC disease referred for bicycle ergometer stress echocardiography (SE) were enrolled ftom July 2019 to January 2021. All patients had measurable tricuspid regurgitation velocity (TRV). Conventional echocardiography parameters, left ventricular global longitudinal strain (LVGLS), RVFWS, and ventriculoarterial coupling indices (TAPSE/SPAP and RVFWS/SPAP) were assessed at rest and peak exercise. Repeat SE was performed at a median follow-up of 2 years. The cohort consisted of 87 patients (mean age was 31 ± 11 years, 66% females). All patients had normal resting TRV < 2.8 m/s, RVFWS and LVGLS at baseline. There were 23 (26%) patients who had peak stress RVFWS < 20%. They had higher resting and peak stress TRV and SPAP, but lower resting and peak stress TAPSE/SPAP, RVFWS/SPAP, and LVGLS as well as lower peak stress cardiac output when compared to patients with peak stress RVFWS ≥ 20% (p < 0.05). Patients with baseline peak stress RVFWS < 20% had a significant decrease in exercise performance at follow-up (7.5 ± 2.7 min at baseline vs. 5.5 ± 2.8 min at follow-up, p < 0.001). In the multivariate analysis, baseline peak stress RVFWS was the only independent predictor of poorer exercise performance at follow-up [odds ratio 8.2 (1.2, 56.0), p = 0.033]. Among patients with SC disease who underwent bicycle ergometer SE, a decreased baseline value of RVFWS at peak stress predicted poorer exercise time at follow-up.

Characteristics of Ischemic Stroke Despite Oral Anticoagulant Use For Atrial Fibrillation.

Oral anticoagulation (OAC) prevents stroke in atrial fibrillation, yet a residual stroke risk remains. In this single-center retrospective analysis of acute ischemic stroke patients despite OAC, suboptimal OAC treatment is common (30%: inappropriate dosing (17%); patient non-adherence (13%)). Other causes of stroke included OAC interruption (14.5%), a competing stroke mechanism (11.0%), and undetermined breakthrough stroke in 44.5%. Overall, easily modifiable causes of ischemic stroke despite OAC are common. Accordingly, strategies to improve treatment compliance, including appropriate dosing along with guideline-based risk factor and periprocedural OAC management, should be emphasized to improve secondary stroke prevention in this patient population.

Fluorinated borono-phenylalanine for optimizing BNCT: Enhancing boron absorption against hydrogen scattering for thermal neutrons.

BACKGROUND: Boron-containing compounds, such as 4-borono-phenylalanine (BPA) are used as drugs for cancer treatment in the framework of Boron Neutron Capture Therapy (BNCT). Neutron irradiation of boron-rich compounds delivered to cancer cells triggers nuclear reactions that destroy cancer cells. PURPOSE: We provide a modeling of the thermal neutron cross section of BPA, a drug used in Boron Neutron Capture Therapy (BNCT), to quantify the competing contributions of boron absorption against hydrogen scattering, for optimizing BNCT by minimizing the latter. METHODS: We perform the experimental determination of the total neutron scattering cross section of BPA at thermal and epithermal neutron energies using neutron transmission measurements. We isolate the contribution related to the incoherent scattering by hydrogen atoms as a function of the neutron energy by means of the Average Functional Group Approximation, and we calculate the probability for a neutron of being absorbed as a function of the neutron energy both for BPA and for its variants where either one or all four aromatic hydrogen atoms are substituted by 19 F, and both for the samples with natural occurrence or enriched concentration of 10 B. RESULTS: While referring to the already available literature for in vivo use of fluorinated BPA, we show that fluorine-rich variants of BPA increase the probability of neutrons being captured by the molecule. As the higher absorption efficiency of fluorinated BPA does not depend on whether the molecule is used in vivo or not, our results are promising for the higher efficiency of the boron neutron capture treatment. CONCLUSIONS: Our results suggest a new advantage using fluorinated compounds for BNCT, in their optimized interaction with neutrons, in addition to their already known capability to be used for monitoring and pharmacokinetics studies using 19 F-Nuclear Magnetic Resonance or in 18 F-Positron Emission Tomography.

Molecular specificity in neutron imaging: the case of hydrogen adsorption in metal organic frameworks.

Neutron imaging is the technique of choice for a number of in situ and operando applications, where a high penetration power is required. White-beam neutron imaging and energy-resolved Bragg edge imaging are successful techniques, the former for the detection of specific elements characterized by strong neutron attenuation and the latter for studying crystal structures. Here we discuss the capabilities of energy-selective neutron imaging taking advantage of the incoherent and inelastic scattering interactions in hydrogenous materials, as a way to obtain molecular-specific information about the composition of a given sample. While few examples from the available literature are discussed, a worked example is presented based on new experimental data on molecular-hydrogen adsorption and conversion in the HKUST-1 metal organic framework.

CO2-mineralization and carbonation reactor rig: Design and validation for in situ neutron scattering experiments-Engineering and lessons learned.

CO2 mineralization via aqueous Mg/Ca/Na-carbonate (MgCO3/CaCO3/Na2CO3) formation represents a huge opportunity for the utilization of captured CO2. However, large-scale mineralization is hindered by slow kinetics due to the highly hydrated character of the cations in aqueous solutions (Mg2+ in particular). Reaction conditions can be optimized to accelerate carbonation kinetics, for example, by the inclusion of additives that promote competitive dehydration of Mg2+ and subsequent agglomeration, nucleation, and crystallization. For tracking mineralization and these reaction steps, neutron scattering presents unprecedented advantages over traditional techniques for time-resolved in situ measurements. However, a setup providing continuous solution circulation to ensure reactant system homogeneity for industrially relevant CO2-mineralization is currently not available for use on neutron beamlines. We, therefore, undertook the design, construction, testing and implementation of such a self-contained reactor rig for use on selected neutron beamlines at the ISIS Neutron and Muon Source (Harwell, UK). The design ensured robust attachment via suspension from the covering Tomkinson flange to stabilize the reactor assembly and all fittings (~25 kg), as well as facilitating precise alignment of the entire reactor and sample (test) cell with respect to beam dimension and direction. The assembly successfully accomplished the principal tasks of providing a continuous flow of the reaction mixture (~500 mL) for homogeneity, quantitative control of CO2 flux into the mixture, and temperature and pressure regulation throughout the reaction and measurements. The design is discussed, with emphasis placed on the reactor, including its geometry, components, and all technical specifications. Descriptions of the off-beamline bench tests, safety, and functionality, as well as the installation on beamlines and trial experimental procedure, are provided, together with representative raw neutron scattering results.

Characterization of Conductive Carbon Nanotubes/Polymer Composites for Stretchable Sensors and Transducers.

The increasing interest in stretchable conductive composite materials, that can be versatile and suitable for wide-ranging application, has sparked a growing demand for studies of scalable fabrication techniques and specifically tailored geometries. Thanks to the combination of the conductivity and robustness of carbon nanotube (CNT) materials with the viscoelastic properties of polymer films, in particular their stretchability, "surface composites" made of a CNT on polymeric films are a promising way to obtain a low-cost, conductive, elastic, moldable, and patternable material. The use of polymers selected for specific applications, however, requires targeted studies to deeply understand the interface interactions between a CNT and the surface of such polymer films, and in particular the stability and durability of a CNT grafting onto the polymer itself. Here, we present an investigation of the interface properties for a selected group of polymer film substrates with different viscoelastic properties by means of a series of different and complementary experimental techniques. Specifically, we studied the interaction of a single-wall carbon nanotube (SWCNT) deposited on two couples of different polymeric substrates, each one chosen as representative of thermoplastic polymers (i.e., low-density polyethylene (LDPE) and polypropylene (PP)) and thermosetting elastomers (i.e., polyisoprene (PI) and polydimethylsiloxane (PDMS)), respectively. Our results demonstrate that the characteristics of the interface significantly differ for the two classes of polymers with a deeper penetration (up to about 100 µm) into the polymer bulk for the thermosetting substrates. Consequently, the resistance per unit length varies in different ranges, from 1-10 kΩ/cm for typical thermoplastic composite devices (30 µm thick and 2 mm wide) to 0.5-3 MΩ/cm for typical thermosetting elastomer devices (150 µm thick and 2 mm wide). For these reasons, the composites show the different mechanical and electrical responses, therefore suggesting different areas of application of the devices based on such materials.

Changes in the hydrogen nuclear kinetic energy across the several phases of methylammonium lead tribromide.

We present an experimental investigation of methylammonium lead tribromide single crystals in the orthorhombic, tetragonal, and cubic phases based on inelastic and deep inelastic neutron scattering experiments. We show how the average hydrogen nuclear kinetic energy, mainly affected by zero-point vibrational energies, shows differences larger compared to the changes simply related to temperature effects when moving from one phase to another. In particular, the Gaussian contribution to the average nuclear kinetic energy is larger in the tetragonal phase compared to the cubic and orthorhombic ones. Moreover, we find that the vibrational densities of states of MAPbBr3 single crystals in the orthorhombic phase are compatible with previously reported results on powder samples, and that the only vibrational modes that show slightly different frequencies compared to MAPbI3 are those in the energy range between 100 and 300 cm-1, related to librational/rotational modes. As these shifts are of about 10 cm-1 and do not affect any higher-energy vibrational mode, we conclude that the zero-point energies and average nuclear kinetic energies in the two-hybrid organic/inorganic perovskites are expected to be approximately the same within a harmonic framework.

Closing the door in front of a torrential mitral regurgitation.

BACKGROUND: Treatment of symptomatic severe mitral regurgitation (MR) is challenging in patients who are not candidates for surgical intervention. CASE DESCRIPTION: We report the case of a 64-year-old female with multiple comorbidities who was found to have severe MR due to a large mitral valve non coaptation. CONCLUSIONS: In this case report, we show the potential of transcatheter edge-to-edge mitral valve repair using MitraClip for the treatment of torrential MR due to a large mitral valve non-coaptation in a patient with no prior history of coronary artery disease and in whom surgical intervention was not an option.

Glass Transition in Rice Pasta as Observed by Combined Neutron Scattering and Time-Domain NMR.

Experimental protocols aiming at the characterisation of glass transition often suffer from ambiguity. The ambition of the present study is to describe the glass transition in a complex, micro heterogeneous system, the dry rice pasta, in a most unambiguous manner, minimising the influence of technique-specific bias. To this end, we apply an unprecedented combination of experimental techniques. Apart from the usually used NMR and DSC, we employ, in a concurrent manner, neutron transmission, diffraction, and Compton scattering. This enables us to investigate the glass transition over a range of spatio-temporal scales that stretches over seven orders of magnitude. The results obtained by neutron diffraction and DSC reveal that dry rice pasta is almost entirely amorphous. Moreover, the glass transition is evidenced by neutron transmission and diffraction data and manifested as a significant decrease of the average sample number density in the temperature range between 40 and 60 °C. At the microscopic level, our NMR, neutron transmission and Compton scattering results provide evidence of changes in the secondary structure of the starch within the dry rice pasta accompanying the glass transition, whereby the long-range order provided by the polymer structure within the starch present in the dry rice pasta is partially lost.

The impact of a perceptual learning module on novices' ability to visually estimate left ventricular ejection fraction by transesophageal echocardiography: a randomized controlled study.

PURPOSE: Echocardiography is a difficult tool to master. Competency requires the supervised interpretation of hundreds of exams. Perceptual learning modules (PLMs) are novel learning tools that aim to speed up this learning process by enabling learners to go online and interpret numerous clinical images, followed systematically by expert feedback. We developed and tested a PLM aimed at improving novices' ability to quickly visually estimate left ventricular ejection fraction (LVEF) on transesophageal echocardiography images, a critical skill in acute care. We hypothesized that using the PLM would improve the accuracy and the speed of learners' estimations. METHODS: Learners without echocardiography experience were randomly assigned to a group that used the 96-case PLM (n = 26) or a control group (n = 26) that did not. Both groups took a pre-test and an immediate post-test that measured the accuracy of their visual estimations during a first session. At six months, participants also completed a delayed post-test. RESULTS: In the immediate post-test, the PLM group showed significantly better accuracy than the control group (median absolute estimation error 6.1 vs 9.0; difference 95% CI, 1.0 to 4.6; P < 0.001). Nevertheless, at six months, estimation errors were similar in both groups (median absolute estimation error 10.0 vs 10.0; difference 95% CI, -1.3 to 2.1; P = 0.27). CONCLUSIONS: Participation in a short online PLM significantly improved novices' short-term ability to accurately estimate LVEF visually, compared with controls. The effect was not sustained at six months. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT03245567); registered 7 August 2017.

RéSUMé: OBJECTIF: L'échocardiographie est un outil difficile à maîtriser. Afin d'acquérir cette compétence, l'interprétation supervisée de centaines d'examens est nécessaire. Les modules d'apprentissage perceptuel (MAP) sont des outils d'apprentissage innovants qui visent à accélérer ce processus d'apprentissage en permettant aux apprenants d'aller en ligne et d'interpréter de nombreuses images cliniques, lesquelles sont systématiquement suivies par des rétroactions d'experts. Nous avons mis au point et testé un MAP visant à améliorer la capacité des nouveaux apprenants à rapidement estimer visuellement la fraction d'éjection ventriculaire gauche (FEVG) sur des images d'échocardiographie transœsophagienne, une compétence critique dans les soins aigus. Nous avons émis l'hypothèse que l'utilisation du MAP améliorerait la précision et la rapidité des estimations des apprenants. MéTHODE: Les apprenants sans expérience de lecture d'échocardiographie ont été aléatoirement alloués à un groupe qui a utilisé le MAP de 96 cas (n = 26) ou à un groupe témoin (n = 26) qui ne l'a pas utilisé. Les deux groupes ont passé un prétest et un post-test immédiat qui ont mesuré l'exactitude de leurs estimations visuelles au cours d'une première séance. Six mois plus tard, les participants ont également passé un autre post-test retardé. RéSULTATS: Dans le post-test immédiat, le groupe MAP a démontré une précision significativement meilleure que le groupe témoin (erreur d'estimation absolue médiane, 6,1 vs 9,0; différence de l'IC 95 %, 1,0 à 4,6; P < 0,001). Néanmoins, à six mois, les erreurs d'estimation étaient similaires dans les deux groupes (erreur d'estimation absolue médiane, 10,0 vs 10,0; différence de l'IC 95 %, -1,3 à 2,1; P = 0,27). CONCLUSION: La participation à un bref MAP en ligne a considérablement amélioré la capacité à court terme des nouveaux apprenants à estimer visuellement et avec précision la FEVG, par rapport à un groupe témoin. L'effet n'était pas maintenu à six mois. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT03245567); enregistrée le 7 août 2017.

Looking for Minor Phenolic Compounds in Extra Virgin Olive Oils Using Neutron and Raman Spectroscopies.

Extra virgin olive oil (EVOO) is defined as a functional food as it contains numerous phenolic components with well-recognized health-beneficial properties, such as high antioxidant and anti-inflammatory capacity. These characteristics depend on their structural/conformational behavior, which is largely determined by intra- and intermolecular H-bond interactions. While the vibrational dynamics of isolated compounds have been studied in a number of recent investigations, their signal in a real-life sample of EVOO is overwhelmed by the major constituent acids. Here, we provide a full characterization of the vibrational spectroscopic signal from commercially available EVOO samples using Inelastic Neutron Scattering (INS) and Raman spectroscopies. The spectra are dominated by CH2 vibrations, especially at about 750 cm-1 and 1300 cm-1. By comparison with the spectra from hydroxytyrosol and other minor phenolic compounds, we show that the best regions in which to look for the structure-activity information related to the minor polar compounds is at 675 and 1200 cm-1 for hydroxytyrosol, and around 450 cm-1 for all minor polar compounds used as reference, especially if a selectively deuterated sample is available. The regional origin of the EVOO samples investigated appears to be related to the different amount of phenolic esters versus acids as reflected by the relative intensities of the peaks at 1655 and 1747 cm-1.

Thermal neutron cross sections of amino acids from average contributions of functional groups.

The experimental thermal neutron cross sections of the 20 proteinogenic amino acids have been measured over the incident-neutron energy range spanning from 1 meV to 10 keV and data have been interpreted using the multi-phonon expansion based on first-principles calculations. The scattering cross section, dominated by the incoherent inelastic contribution from the hydrogen atoms, can be rationalised in terms of the average contributions of different functional groups, thus neglecting their correlation. These results can be used for modelling the total neutron cross sections of complex organic systems like proteins, muscles, or human tissues from a limited number of starting input functions. This simplification is of crucial importance for fine-tuning of transport simulations used in medical applications, including boron neutron capture therapy as well as secondary neutrons-emission induced during proton therapy. Moreover, the parametrized neutron cross sections allow a better treatment of neutron scattering experiments, providing detailed sample self-attenuation corrections for a variety of biological and soft-matter systems.

Proton Dynamics in Palladium-Silver: An Inelastic Neutron Scattering Investigation.

Proton dynamics in Pd77Ag23 membranes is investigated by means of various neutron spectroscopic techniques, namely Quasi Elastic Neutron Scattering, Incoherent Inelastic Neutron Scattering, Neutron Transmission, and Deep Inelastic Neutron Scattering. Measurements carried out at the ISIS spallation neutron source using OSIRIS, MARI and VESUVIO spectrometers were performed at pressures of 1, 2, and 4 bar, and temperatures in the 330-673 K range. The energy interval spanned by the different instruments provides information on the proton dynamics in a time scale ranging from about 102 to 10-4 ps. The main finding is that the macroscopic diffusion process is determined by microscopic jump diffusion. In addition, the vibrational density of states of the H atoms in the metal lattice has been determined for a number of H concentrations and temperatures. These measurements follow a series of neutron diffraction experiments performed on the same sample and thus provide a complementary information for a thorough description of structural and dynamical properties of H-loaded Pd-Ag membranes.

The effective isotropy of the hydrogen local potential in biphenyl and other hydrocarbons.

We present an experimental investigation of the hydrogen nuclear momentum distribution in biphenyl using deep inelastic neutron scattering. Our experimental results suggest that the local potential affecting hydrogen is both harmonic and isotropic within experimental uncertainties. This feature is interpreted as a consequence of the central limit theorem, whereby the three-dimensional momentum distribution is expected to become a purely Gaussian function as the number of independent vibrational modes in a system increases. We also performed ab initio phonon calculations on biphenyl and other saturated hydrocarbons, from methane to decane. From the results of the simulations, one can observe that the nuclear momentum distribution becomes more isotropic as the number of atoms and normal modes in the molecule increases. Moreover, the predicted theoretical anisotropy in biphenyl is clearly larger than in the experiment. The reason is that the total number of normal modes necessary to reproduce the experimental results is much larger than the number of normal modes encompassed by a single unit cell due to the presence of structural disorder and intermolecular interactions in the real crystal, as well as coupling of different normal modes. Finally, experimental data were collected, over a subset of detectors on the VESUVIO spectrometer at ISIS, with a novel setup to increase the count rate and signal-to-background ratio. We envision that such an optimized experimental setup can provide faster measurements and more stringent constraints for phonon calculations.

A Python Algorithm to Analyze Inelastic Neutron Scattering Spectra Based on the y-Scale Formalism.

This paper presents a Python-based algorithm, named INSCorNorm, to correct the inelastic neutron scattering (INS) spectra for both sample and container self-shielding and to normalize the experimental spectral intensity to an absolute physical scale (barn/energy unit) facilitating the comparison with computer simulations and interpretation. The algorithm is benchmarked against INS measurements of ZrH2 performed on the TOSCA spectrometer at the ISIS Facility. We also apply the algorithm to the INS spectra from l-lysine, a system of broad interest in biology and medicine, and we discuss how corrected INS data provide an experimental benchmark for theoretical calculations of nuclear anisotropic displacement parameters in molecular systems. The total neutron sample cross section to use for the self-shielding corrections is discussed, as well as the best approach to derive experimentally the cross section at the VESUVIO spectrometer, together with the experimental value of the hydrogen nuclear mean kinetic energy, ⟨Ek⟩. The algorithm is made available to the neutron user community within the MANTID software.

Hydrogen nuclear mean kinetic energy in water down the Mariana Trench: Competition of pressure and salinity.

The Mariana Trench is one of the most famous and extreme environments on our planet. We report experimental values of the hydrogen nuclear mean kinetic energy in water samples at the same physical and chemical conditions than in the Challenger Deep within the Mariana Trench: a pressure of 1092 bars, a temperature of 1 °C, and a salinity of 35 g of salt per kg of water. Results were obtained by deep inelastic neutron scattering at the VESUVIO spectrometer at ISIS. We find that the effect of pressure is to increase the hydrogen nuclear mean kinetic energy with respect to ambient conditions, while ions in the solution have the opposite effect. These results confirm the recent state-of-the-art simulations of the nuclear hydrogen dynamics in water. The changes in the nuclear mean kinetic energy likely correspond to different isotopic fractionation values in the Challenger Deep compared to standard sea water.

Hydrogen Dynamics in Supercritical Water Probed by Neutron Scattering and Computer Simulations.

In this work, an investigation of supercritical water is presented combining inelastic and deep inelastic neutron scattering experiments and molecular dynamics simulations based on a machine-learned potential of ab initio quality. The local hydrogen dynamics is investigated at 250 bar and in the temperature range of 553-823 K, covering the evolution from subcritical liquid to supercritical gas-like water. The evolution of libration, bending, and stretching motions in the vibrational density of states is studied, analyzing the spectral features by a mode decomposition. Moreover, the hydrogen nuclear momentum distribution is measured, and its anisotropy is probed experimentally. It is shown that hydrogen bonds survive up to the higher temperatures investigated, and we discuss our results in the framework of the coupling between intramolecular modes and intermolecular librations. Results show that the local potential affecting hydrogen becomes less anisotropic within the molecular plane in the supercritical phase, and we attribute this result to the presence of more distorted hydrogen bonds.

Neutrons for Cultural Heritage-Techniques, Sensors, and Detection.

Advances in research in Cultural Heritage see increasing application of a multidisciplinary approach and the combined use of physical and chemical characterization of artefacts that can be used to define their structure and their state of conservation, also providing valuable information in selecting the most suitable microclimatic conditions for the exhibition environment. This approach provides a platform for a synergic collaboration amongst researchers, restorers, conservators, and archaeologists. Existing state-of-the-art technologies for neutron-based methods are currently being applied to the study of objects of historical and cultural interest in several neutron-beam facilities around the world. Such techniques are non-invasive and non-destructive and are, therefore, ideal to provide structural information about artefacts, such as their composition, presence of alterations due to the environmental conditions, inclusions, structure of the bulk, manufacturing techniques, and elemental composition, which provide an overall fingerprint of the object's characteristics, thanks to the nature of the interaction of neutrons with matter. Here, we present an overview of the main neutron methods for the characterization of materials of interest in Cultural Heritage and we provide a brief introduction to the sensors and detectors that are used in this framework. We conclude with some case studies underlining the impact of these applications in different archaeological and historical contexts.

Left ventricular structural and functional changes in Friedreich ataxia - Relationship with body size, sex, age and genetic severity.

INTRODUCTION: Although a concentric pattern of left ventricular (LV) geometry appears to be common in Friedreich ataxia (FRDA), there is no accepted method for diagnosing LV abnormalities in FRDA, sex and body size have often not been taken into consideration, and it has not been clear whether children and adults should be classified using the same criteria. The aim of this study was to better define the LV geometric changes in FRDA with respect to sex, body size and subject age, and to investigate the relationship of LV changes with genetic severity, as assessed by GAA repeat length within the shorter allele of the FXN gene (GAA1). METHODS: Echocardiography was performed in 216 subjects (68 children, 148 adults), measurements were made at end-diastole of LV internal diameter (LVEDID), septal wall thickness (SWT), LV length (LVEDL) and LV volume (LVEDV), and calculations were made of relative wall thickness (RWT), LV mass and LV ejection fraction (LVEF). RESULTS: The most common LV abnormalities in both adults and children with FRDA were increases in RWT and age-normalized RWT. In adults with a normal LVEF, all LV variables other than RWT were larger in males independent of body surface area (BSA), and all LV variables other than SWT and RWT were positively correlated with BSA. After adjustment for sex and BSA, GAA1 was a positive correlate of SWT and RWT (but not of LV mass), and was an inverse correlate of LVEDID, LVEDL and LVEDV. In children with a normal LVEF, SWT, LV mass and LVEDL were larger in males than females after adjusting for BSA, and in combination with sex, BSA was a positive correlate of all the LV variables except SWT and RWT. In children there were no correlations of GAA1 with any of the LV variables. CONCLUSION: In FRDA, increases in RWT and age-normalized RWT are the most frequent LV structural abnormalities, sex and body size are important determinants of most other LV structural variables in both children and adults, and increased genetic severity is associated with a smaller left ventricle and increased LV wall thickness in adults, but not associated with LV size or wall thickness in children.