Cardiotoxicity in cancer patients: beyond the left ventricular ejection fraction.

Life-expectancy for patients with cancer is steadily improving, with an increasing rate of treatment related complications. Antineoplastic therapy employed in cancer treatment is frequently complicated by the development of cardiotoxicity. Cardiovascular complications can be different, ranging from heart failure, myocardial ischemia or infarction to hypertension, arrhythmias and thromboembolism. It is therefore mandatory to early recognize and treat cardiovascular side effects related to chemotherapy drugs. Echocardiography has been and it is still the cornerstone in the diagnosis and follow-up of cardiac dysfunction due to its availability, safety and versatility. The most used parameter to evaluate cardiac dysfunction in this context is the left ventricular ejection fraction (LVEF) and current European Society of Echocardiography and American Society of Echocardiography guidelines for the evaluation of adult patients during and after cancer therapy are based on LVEF. However this parameter has several limits and may mask cardiac dysfunction. Recently developed strain imaging may provide a more sensitive and early detection of altered left ventricular function. In the present study we evaluated 53 patients (age 53 ± 13 years, women 64%) on cancer drug therapies referred to the cardio-oncology clinic of the Royal Brompton Hospital in London. All patients had 2D echo-derived LVEF ≥55% and echo images suitable to speckle tracking analysis for global longitudinal (GLS), circumferential (GCS) and radial strain (GRS). Concomitant troponin I and BNP levels were measured and 43 (81%) patients underwent CMR imaging. The 2D strain data were compared to 25 healthy age matched controls using the student t test. Conventional echocardiographic parameters were substantially normal, including diastolic measurements All strain parameters were significantly lower in patients on cancer drug therapies compared to controls. In the cancer population (n=53) we found mean global peak systolic values of global longitudinal strain (GLS) global circumferential strain (GCS) and global radial strain (GRS) respectively of -19.8 ± 3.3%, -23.4 ± 4.8% and 29.7 ± 14%. In the 25 controls strain imaging values were respectively -22 ± 2% for GLS, -29.5 ± 5% for GCS and 42 ± 10% for GRS. CMR showed loss of torsion and/or fibrosis in 10(23%) patients with no correlation to strain values. BNP was elevated in 34(64%) patients with no differences in strain values compared to those with normal BNP values. Troponin I was elevated in only one patient. Intra-observer reproducibility carried out in a subgroup of 20 random selected cancer patients revealed good correlation for global longitudinal and circumferential strain (ICC 0.8; r=0.7) and moderate correlation for global radial strain (ICC 0.7; r=0.6) while inter-observer variability showed moderate correlation for all the three parameters (ICC 0.7; r=0.5). In our study cancer patients on current chemotherapy drugs with preserved left ventricular ejection fraction (LVEF ≥ 55%) showed significantly lower GLS, GCS and GRS values when compared to our echo-lab normal reference values (p<.05). In our study, despite having a normal LVEF, patients on cancer drug therapies had evidence of sub-clinical myocardial dysfunction affecting all myocardial layers and in particular radial function. Strain can be therefore a sensitive tool to detect early chemotherapy related cardiotoxicity and to prevent morbidity and mortality through close follow-up and appropriate cardiac therapy. CMR findings and BNP levels may provide additional complementary information. The clinical relevance of these findings requires further study

Synthesis and characterization of multiferroic BiMn7_7O12_{12}

We report on the high pressure synthesis of BiMn$_7$O$_{12}$, a manganite displaying a "quadruple perovskite" structure. Structural characterization of single crystal samples shows a distorted and asymmetrical coordination around the Bi atom, due to presence of the $6s^{2}$ lone pair, resulting in non-centrosymmetric space group Im, leading to a permanent electrical dipole moment and ferroelectric properties. On the other hand, magnetic characterization reveals antiferromagnetic transitions, in agreement with the isostructural compounds, thus evidencing two intrinsic properties that make BiMn$_7$O$_{12}$ a promising multiferroic material.Comment: 4 pages, 3 figure

Internal-strain mediated coupling between polar Bi and magnetic Mn ions in the defect-free quadruple-perovskite BiMn3_3Mn4_4O12_{12}

By means of neutron powder diffraction, we investigated the effect of the polar Bi$^{3+}$ ion on the magnetic ordering of the Mn$^{3+}$ ions in BiMn$_3$Mn$_4$O$_{12}$, the counterpart with \textit{quadruple} perovskite structure of the \textit{simple} perovskite BiMnO$_3$. The data are consistent with a \textit{noncentrosymmetric} spacegroup $Im$ which contrasts the \textit{centrosymmetric} one $I2/m$ previously reported for the isovalent and isomorphic compound LaMn$_3$Mn$_4$O$_{12}$, which gives evidence of a Bi$^{3+}$-induced polarization of the lattice. At low temperature, the two Mn$^{3+}$ sublattices of the $A'$ and $B$ sites order antiferromagnetically (AFM) in an independent manner at 25 and 55 K, similarly to the case of LaMn$_3$Mn$_4$O$_{12}$. However, both magnetic structures of BiMn$_3$Mn$_4$O$_{12}$ radically differ from those of LaMn$_3$Mn$_4$O$_{12}$. In BiMn$_3$Mn$_4$O$_{12}$ the moments $\textbf{M}_{A'}$ of the $A'$ sites form an anti-body AFM structure, whilst the moments \textbf{M}$_{B}$ of the $B$ sites result from a large and \textit{uniform} modulation $\pm \textbf{M}_{B,b}$ along the b-axis of the moments \textbf{M}$_{B,ac}$ in the $ac$-plane. The modulation is strikingly correlated with the displacements of the Mn$^{3+}$ ions induced by the Bi$^{3+}$ ions. Our analysis unveils a strong magnetoelastic coupling between the internal strain created by the Bi$^{3+}$ ions and the moment of the Mn$^{3+}$ ions in the $B$ sites. This is ascribed to the high symmetry of the oxygen sites and to the absence of oxygen defects, two characteristics of quadruple perovskites not found in simple ones, which prevent the release of the Bi$^{3+}$-induced strain through distortions or disorder. This demonstrates the possibility of a large magnetoelectric coupling in proper ferroelectrics and suggests a novel concept of internal strain engineering for multiferroics design.Comment: 9 pages, 7 figures, 5 table

Effect of temperature on the mutual diffusion of Ge/GaAs and GaAs/Ge

GaAs/Ge heterostructures are commonly used in high efficiency solar cell: structures such as InGaP/GaAs/GaAs or GaAs/Ge and triple junction InGaP/GaAs/Ge, are continuously improving their efficiency. Sharp heterointerfaces and abrupt dopant profiles are essential in order to obtain a good control of the heteroepitaxy. One common problem in the Ge/GaAs, GaAs/Ge, Ge/GaAs/Ge, Ge/GaAs/GaAs, GaAs/Ge/GaAs and GaAs/Ge/Ge heterostructures is the interdiffusion of the elements in the different layers, i.e. Ge in GaAs and Ga and As in Ge. Since Ge acts as dopant in GaAs, and vice-versa, the film/substrate interdiffusion of Ge and GaAs is able to change the carrier concentrations in the layers. In order to assess this problem we grew Ge/GaAs and GaAs/Ge heterojunctions by metal-organic vapour phase epitaxy (MOVPE) using iso-butylgermane, arsine and trimethylgallium in hydrogen atmosphere at low pressure, varying the deposition temperature. The use of low temperature GaAs and Ge buffer layers was investigated in order to limit the interdiffusion. Different experimental techniques, including Secondary Neutral Mass Spectrometry (SNMS), High Resolution X-ray Diffraction (HR-XRD), Transmission Electron Microscopy (TEM), Rutherford Backscattering Spectrometry combined with Channeling technique (RBS/C) and Atomic Force Microscopy (AFM) have been used to investigate the samples. HR-XRD profiles show the good crystalline quality of the epitaxial layers, with a lattice mismatch between the layer and the substrate as calculated form the peak separation corresponding to perfectly adapted layers RBS/channeling spectra show no significant difference between the samples grown at different temperatures, indicating that the presence of extra defects, strain, or misorientation at the interface is below the detection limit. The depth profile analysis of samples measured by SNMS show remarkable interdiffusion of all components at the heterointerfaces between the layers and substrates, indicates a variation with temperature. The results confirmed that a low temperature GaAs buffer layer could efficiently reduce GaAs/Ge mutual diffusion. The same is not true for a low temperature Ge buffer layer in Ge/GaAs epitaxy. TEM was used to assess the crystal quality of the grown layers and composition distribution by X-ray microanalysis, that confirmed elements interdiffusion as measured by SNMS

The Solidarity Manifesto: A New Network for Future Change

Colonialism is a scheme of standpoint; colonizer versus colonized, West versus East, good versus bad. When put in the foreground, the value of what we see heavily relies on our perspective and knowledge. When learning to dissect, deconstruct, and decolonize spaces, we need to start utilizing decolonial thought as an historical tool rather than a true depiction of reality. Decolonizing spaces and recognizing Western colonization practices means challenging the normative structures in colonial history, thus breaking the cycle of oppression through building community and fostering solidarity. Drawing on theories exploring access to public spheres, representation, protection, permanence, cultural displacement and the creation of crosscultural ecosystems, this study gives special highlight to the (dis)connection between global policy processes and local initiatives through a decolonial feminist lens. Prescribing the need for decolonial discourses in helping bridge the gap between the literary and physical spaces that inform decision-making bodies today, this thesis places emphasis on Françoise Vergès’ A Decolonial Feminism and A Feminist Theory of Violence: A Decolonial Perspective to inform solidarity-centered approaches to future change in policy making. Through a decolonial case study analysis of the Italian occupation of Libya, the exclusive power of language, and observations of NGO work at the United Nations, and by proposing the Solidarity Model based on accountability and representation, the aim of this study is to deconstruct current systems and their discourses to explore future international networks based on human solidarit

Proton-proton elastic scattering at the LHC energy of {\surd} = 7 TeV

Proton-proton elastic scattering has been measured by the TOTEM experiment at the CERN Large Hadron Collider at {\surd}s = 7 TeV in dedicated runs with the Roman Pot detectors placed as close as seven times the transverse beam size (sbeam) from the outgoing beams. After careful study of the accelerator optics and the detector alignment, |t|, the square of four-momentum transferred in the elastic scattering process, has been determined with an uncertainty of d t = 0.1GeV p|t|. In this letter, first results of the differential cross section are presented covering a |t|-range from 0.36 to 2.5GeV2. The differential cross-section in the range 0.36 < |t| < 0.47 GeV2 is described by an exponential with a slope parameter B = (23.6{\pm}0.5stat {\pm}0.4syst)GeV-2, followed by a significant diffractive minimum at |t| = (0.53{\pm}0.01stat{\pm}0.01syst)GeV2. For |t|-values larger than ~ 1.5GeV2, the cross-section exhibits a power law behaviour with an exponent of -7.8_\pm} 0.3stat{\pm}0.1syst. When compared to predictions based on the different available models, the data show a strong discriminative power despite the small t-range covered.Comment: 12pages, 5 figures, CERN preprin

Muon Energy Estimate Through Multiple Scattering with the Macro Detector

Muon energy measurement represents an important issue for any experiment addressing neutrino induced upgoing muon studies. Since the neutrino oscillation probability depends on the neutrino energy, a measurement of the muon energy adds an important piece of information concerning the neutrino system. We show in this paper how the MACRO limited streamer tube system can be operated in drift mode by using the TDC's included in the QTPs, an electronics designed for magnetic monopole search. An improvement of the space resolution is obtained, through an analysis of the multiple scattering of muon tracks as they pass through our detector. This information can be used further to obtain an estimate of the energy of muons crossing the detector. Here we present the results of two dedicated tests, performed at CERN PS-T9 and SPS-X7 beam lines, to provide a full check of the electronics and to exploit the feasibility of such a multiple scattering analysis. We show that by using a neural network approach, we are able to reconstruct the muon energy for $E_\mu<$40 GeV. The test beam data provide an absolute energy calibration, which allows us to apply this method to MACRO data.Comment: 25 pages, 11 figures, Submitted to Nucl. Instr. & Meth.

The Observation of Up-going Charged Particles Produced by High Energy Muons in Underground Detectors

An experimental study of the production of up-going charged particles in inelastic interactions of down-going underground muons is reported, using data obtained from the MACRO detector at the Gran Sasso Laboratory. In a sample of 12.2 10^6 single muons, corresponding to a detector livetime of 1.55 y, 243 events are observed having an up-going particle associated with a down-going muon. These events are analysed to determine the range and emission angle distributions of the up-going particle, corrected for detection and reconstruction efficiency. Measurements of the muon neutrino flux by underground detectors are often based on the observation of through-going and stopping muons produced in $\nu_\mu$ interactions in the rock below the detector. Up-going particles produced by an undetected down-going muon are a potential background source in these measurements. The implications of this background for neutrino studies using MACRO are discussed.Comment: 18 pages, 9 figures. Accepted by Astrop. Physic

Search for Nucleon Decays induced by GUT Magnetic Monopoles with the MACRO Experiment

The interaction of a Grand Unification Magnetic Monopole with a nucleon can lead to a barion-number violating process in which the nucleon decays into a lepton and one or more mesons (catalysis of nucleon decay). In this paper we report an experimental study of the effects of a catalysis process in the MACRO detector. Using a dedicated analysis we obtain new magnetic monopole (MM) flux upper limits at the level of $\sim 3\cdot 10^{-16} cm^{-2} s^{-1} sr^{-1}$ for $1.1\cdot 10^{-4} \le |\beta| \le 5\cdot 10^{-3}$, based on the search for catalysis events in the MACRO data. We also analyze the dependence of the MM flux limit on the catalysis cross section.Comment: 12 pages, Latex, 10 figures and 2 Table