In chagasic patients, the electrocardiogram becomes abnormal very late in the course of the disease. Most clinical studies concerning cardiac autonomic function of chagasic patients have been carried ...out in this very late stage of the disease. The purpose of this study was to assess accurately the left ventricular systolic function of chagasic patients with abnormal electrocardiograms. We performed left ventricular contrast cineangiography in 44 patients with positive complement fixation test for Chagas' disease and abnormal electrocardiograms. On the basis of the electrocardiographic abnormalities found in the electrocardiogram taken the night before the hemodynamic procedure, we divided our patients into three subgroups; those with rhythm disturbances, those with ventricular conduction abnormalities, and those with rhythm disturbances plus ventricular conduction abnormalities. The chagasic patients with only cardiac rhythm disturbances, had left ventricular volumes and ejection fractions which were similar to those of controls. On the other hand, the left ventricular volumes of the chagasic patients with ventricular conduction defects, although slightly larger, were still not different from those of controls. Finally, the chagasic patients, with cardiac rhythm disturbances and left ventricular conduction defects, had the largest left ventricular volumes (P less than 0.05), and the lowest ejection fractions (P less than 0.001) of all three subgroups. These findings clearly indicate that chagasic patients, in this very late stage of the disease, have a very variable degree of left ventricular systolic dysfunction. Furthermore, our results show a distinct tendency for the left ventricular volumes to increase, and for the ejection fraction to decrease; when the electrocardiogram becomes progressively more abnormal, and "mixed" electrocardiographic abnormalities appear.
Gamma-ray source stacking analysis at low galactic latitudes Cillis, Analia N; Reimer, Olaf; Torres, Diego F
The multi-messenger approach to high-energy gamma-ray sources : Third Workshop on the Nature of Unidentified High-Energy Sources,
01/2007
Journal Article
We studied the problematic of uncertainties in the diffuse gamma radiation apparent in stacking analysis of EGRET data at low Galactic latitudes. Subsequently, we co-added maps of counts, exposure ...and diffuse background, and residuals, in varying numbers for different sub-categories of putatively and known source populations (like PSRs). Finally we tested for gamma-ray excess emission in those maps and attempt to quantify the systematic biases in such approach. Such kind of an analysis will help the classification processes of sources and source populations in the GLAST era.
The 2008 outburst of the atoll source IGR J17473--2721 was observed by INTEGRAL, RXTE and Swift. Tens of type-I X-ray bursts were found in this outburst. Joint observations provide sufficient data to ...look into the behavior of IGR J17473--2721 at the rising part of the outburst. We find that the joint energy spectra can be well fitted with a model composed of a blackbody and a cutoff power-law, with a cutoff energy decreasing from \( \sim\) 150 keV to \(\sim\) 40 keV as the source leaves the quiescent state toward the low hard state. This fits into a scenario in which the corona is cooled by the soft X-rays along the outburst evolution, as observed in several other atoll sources. By using the flux measured in the 1.5--30 keV band of the type-I bursts during the outburst, we find that the linear relationship between the burst duration and the flux still holds for those bursts that occur at the decaying part of the low hard state, but with a different slope than the overall one that was estimated with the bursts happening in the whole extent of, and for the rest of the low hard state. The significance of such a dichotomy in the type-I X-ray bursts is \(\sim\) 3 \(\sigma\) under an F-test. Similar results are hinted at as well with the broader energy-band that was adopted recently. This dichotomy may be understood in a scenario where part of the accreting material forms a corona on the way of falling onto the surface of the neutron star during the decaying part of the low hard state. Based on the accretion rates of the preceding LHS, estimated from type-I X-ray bursts and from persistent emission, at least for IGR J17473-2721, most of the accretion material may fall on the neutron star (NS) surface in the LHS. Considering the burst behavior in the context of the outburst indicates a corona formed on top of the disk rather than on the NS surface.
Astrophys.SpaceSci.309:51-55,2007 We studied the problematic of uncertainties in the diffuse gamma radiation
apparent in stacking analysis of EGRET data at low Galactic latitudes.
Subsequently, we ...co-added maps of counts, exposure and diffuse background, and
residuals, in varying numbers for different sub-categories of putatively and
known source populations (like PSRs). Finally we tested for gamma-ray excess
emission in those maps and attempt to quantify the systematic biases in such
approach. Such kind of an analysis will help the classification processes of
sources and source populations in the GLAST era.
Phys.Rev.D56:3478-3484,1997 We study equilibrium configurations of boson stars in the framework of
general scalar-tensor theories of gravitation. We analyse several possible
couplings, with ...acceptable weak field limit and, when known, nucleosynthesis
bounds, in order to work in the cosmologically more realistic cases of this
kind of theories. We found that for general scalar-tensor gravitation, the
range of masses boson stars might have is comparable with the general
relativistic case. We also analyse the possible formation of boson stars along
different eras of cosmic evolution, allowing for the effective gravitational
constant far out form the star to deviate from its current value. In these
cases, we found that the boson stars masses are sensitive to this kind of
variations, within a typical few percent. We also study cases in which the
coupling is implicitly defined, through the dependence on the radial
coordinate, allowing it to have significant variations in the radius of the
structure.
Rept.Prog.Phys.67:1663-1730,2004 In the first part of this review we discuss the basic observational features
at the end of the cosmic ray energy spectrum. We also present there the main
...characteristics of each of the experiments involved in the detection of these
particles. We then briefly discuss the status of the chemical composition and
the distribution of arrival directions of cosmic rays. After that, we examine
the energy losses during propagation, introducing the Greisen-Zaptsepin-Kuzmin
(GZK) cutoff, and discuss the level of confidence with which each experiment
have detected particles beyond the GZK energy limit. In the second part of the
review, we discuss astrophysical environments able to accelerate particles up
to such high energies, including active galactic nuclei, large scale galactic
wind termination shocks, relativistic jets and hot-spots of Fanaroff-Riley
radiogalaxies, pulsars, magnetars, quasar remnants, starbursts, colliding
galaxies, and gamma ray burst fireballs. In the third part of the review we
provide a brief summary of scenarios which try to explain the super-GZK events
with the help of new physics beyond the standard model. In the last section, we
give an overview on neutrino telescopes and existing limits on the energy
spectrum and discuss some of the prospects for a new (multi-particle)
astronomy. Finally, we outline how extraterrestrial neutrino fluxes can be used
to probe new physics beyond the electroweak scale.
Astrophys.J. 603 (2004) L133-L136 A decade ago, it was shown that a wide class of scalar-tensor theories can
pass very restrictive weak field tests of gravity and yet exhibit
non-perturbative strong ...field deviations away from General Relativity. This
phenomenon was called `Spontaneous Scalarization' and causes the (Einstein
frame) scalar field inside a neutron star to rapidly become inhomogeneous once
the star's mass increases above some critical value. For a star whose mass is
below the threshold, the field is instead nearly uniform (a state which
minimises the star's energy) and the configuration is similar to the General
Relativity one. Here, we show that the spontaneous scalarization phenomenon is
linked to another strong field effect: a spontaneous violation of the weak
energy condition.
In the original version of this Article, the affiliation of the first author, Maria F. Torres, 'Department of Biological Sciences, University of Cincinnati, Cincinnati, 45221, OH, USA' was ...incorrectly assigned as a present address and should have been listed as a full affiliation. This error has been corrected in both the PDF and HTML versions of the Article.
1. To assess the efficacy of Mesenchymal Stromal Cells (MSC) versus a control arm as described in the primary endpoint. 2. To evaluate the effects of MSC on the secondary efficacy endpoints. 3. To ...evaluate the safety and tolerability profiles of MSC. 4. To study soluble and cellular biomarkers that might be involved in the course of the disease and the response to the investigational product.
A double-blind, randomized, controlled, trial to evaluate the efficacy and safety of MSC intravenous administration in patients with COVID-induced Acute Respiratory Distress Syndrome (ARDS) compared to a control arm.
The trial is being conducted at a third level hospital, Hospital Universitario Puerta de Hierro, in Majadahonda, Madrid (Spain). Inclusion criteria 1. Informed consent prior to performing study procedures (witnessed oral consent with written consent by representatives will be accepted to avoid paper handling). Written consent by patient or representatives will be obtained whenever possible. 2. Adult patients ≥18 years of age at the time of enrolment. 3. Laboratory-confirmed SARS-CoV-2 infection as determined by Polymerase Chain Reaction (PCR), in oropharyngeal swabs or any other relevant specimen obtained during the course of the disease. Alternative tests (e.g., rapid antigen tests) are also acceptable as laboratory confirmation if their specificity has been accepted by the Sponsor. 4. Moderate to severe ARDS (PaO2/FiO2 ratio equal or less than 200 mmHg) for less than 96 hours at the time of randomization. 5. Patients requiring invasive ventilation are eligible within 72 hours from intubation. 6. Eligible for ICU admission, according to the clinical team. Exclusion criteria 1. Imminent and unavoidable progression to death within 24 hours, irrespective of the provision of treatments (in the opinion of the clinical team). 2. "Do Not Attempt Resuscitation" order in place. 3. Any end-stage organ disease or condition, which in the investigator's opinion, makes the patient an unsuitable candidate for treatment. 4. History of a moderate/severe lung disorder requiring home-based oxygen therapy. 5. Patient requiring Extracorporeal Membrane Oxygenation (ECMO), haemodialysis or hemofiltration at the time of treatment administration. 6. Current diagnosis of pulmonary embolism. 7. Active neoplasm, except carcinoma in situ or basalioma. 8. Known allergy to the products involved in the allogeneic MSC production process. 9. Current pregnancy or lactation (women with childbearing potential should have a negative pregnancy test result at the time of study enrolment). 10. Current participation in a clinical trial with an experimental treatment for COVID-19 (the use of any off-label medicine according to local treatment protocols is not an exclusion criteria). 11. Any circumstances that in the investigator's opinion compromises the patient's ability to participate in the clinical trial. INTERVENTION AND COMPARATOR: - Experimental treatment arm: Allogeneic MSC (approximately 1 x 10
cells/kg). - Control arm: placebo solution (same composition as the experimental treatment, without the MSC). One single intravenous dose of the assigned treatment will be administered on Day 0 of the study. All trial participants will receive standard of care (SOC). In the context of the current worldwide pandemic, SOC can include medicines that are being used in clinical practice (e.g. lopinavir/ritonavir; hydroxy/chloroquine, tocilizumab, etc.), as well as those authorised for COVID (e.g., remdesivir).
Primary endpoint: Change in the PaO2/FiO2 ratio from baseline to day 7 of treatment administration, or to the last available PaO2/FiO2 ratio if death occurs before day 7. Secondary endpoints: - All-cause mortality on days 7, 14, and 28 after treatment. - PaO2/FiO2 ratio at baseline and days 2, 4, 7, 14 and 28 after treatment. - Oxygen saturation (by standardized measurement) at baseline, daily until day 14, and on day 28 after treatment. - Time to PaO2/FiO2 ratio greater than 200 mmHg. - Subjects' clinical status on the WHO 7-point ordinal scale at baseline, daily until day 14, and on day 28 after treatment. - Time to an improvement of one category from admission on the WHO 7-point ordinal scale. - Percentage of patients that worsen at least one category on the WHO 7-point ordinal scale. - Percentage of patients that improve at least one category (maintained 48h) on the WHO 7-point ordinal scale. - Sequential Organ Failure Assessment (SOFA) scale at baseline and days 2, 4, 7, 14 and 28 after treatment. - Duration of hospitalization (days). - Duration of ICU stay (days). - Oxygen therapy-free days in the first 28 days after treatment. - Duration of supplemental oxygen. - Incidence of and duration of non-invasive and invasive mechanical ventilation in the first 28 days after treatment. - Mechanical ventilation-free days in the first 28 days after treatment. - Ventilation parameters. - Incidence of new onset pulmonary fibrosis at 3 and 12 months after treatment, based on CT scan and pulmonary function tests. - Survival at 3 and 12 months. - Cumulative incidence of Serious Adverse events (SAEs) and Grade 3 and 4 Adverse Events (AEs). - Cumulative incidence of Adverse Drug Reactions (ADR) in the experimental treatment arm. - Cumulative incidence of AEs of special interest. - Levels of analytical markers (C-Reactive Protein, lymphocyte and neutrophil counts, lymphocyte subpopulations, LDH, ferritin, D-dimer, coagulation tests and cytokines...) at baseline and days 2, 4, 7, 14 and 28 after treatment. - Other soluble and cellular biomarkers that might be involved in the course of the disease and the response to MSC.
The assignment to treatment will be carried out randomly and blinded, with a 1:1 allocation. Randomization will be done through a centralized system embedded in the electronic Case Report Form (CRF).
To ensure blinding, treatments will be prepared for administration at the Cell Production Unit and the administration of the treatment will be masked, not allowing the identification of the Investigational Medicinal Product (IMP).
A total of 20 participants are planned to be randomized, 10 to each treatment group.
Protocol version: 1.2, dated October 14th, 2020 Start of recruitment: 01/10/2020 End of recruitment (estimated): December 2020.
EudraCT Number: 2020-002193-27 , registered on July 14
, 2020. NCT number: NCT04615429 , registered on November 4
, 2020.
The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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