Chagas disease: Historic perspective

This review is a perspective on the history of Chagas disease, and it adopts a novel approach from literary studies, historical documents and the science and epidemiology of the nature of the disease. From this analysis, comes the review's working definition of the Contact Zone (CZ): “the space in which geographically and historically separated people come into contact with each other and establish long-lasting relationships, which usually involve coercive conditions, radical inequality and intolerable conflict.” In the Patient-Physician CZ, we verified the triple transition phenomena: the American trypanosomiasis shifted from a rural, acute, and vectorial transmitted disease to an urban, chronic and non-vectorial disease. In the Academic CZ, we describe the original disagreements which denied the existence of the disease and the current controversies about pathogenic mechanisms and etiological treatment. From the News from Latin America, and in the Original CZ, we will review the evolution of different forms of transmission. As in any good story, research across broad disciplines is necessary to reveal historical perspectives, scientific approaches, and the epidemiology of the disease, which has a prequel of 9000 years and an open ending: thus, we explore across the Global CZ, with its multiple and unexpected actors.Fil: Chao, Chen. Fundación Favaloro; ArgentinaFil: Leone, José L.. No especifíca;Fil: Vigliano, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentin

Hunting for dark matter and new physics with GECCO

We outline the science opportunities in the areas of searches for dark matter and new physics offered by a proposed future MeV gamma-ray telescope, the Galactic Explorer with a Coded Aperture Mask Compton Telescope (GECCO). We point out that such an instrument would play a critical role in opening up a discovery window for particle dark matter with mass in the MeV or sub-MeV range, in disentangling the origin of the mysterious 511 keV line emission in the Galactic Center region, and in potentially discovering Hawking evaporation from light primordial black holes

Impact of Aetiological Treatment on Conventional and Multiplex Serology in Chronic Chagas Disease

The main criterion for treatment effectiveness in Chagas Disease has been the seronegative conversion of previously reactive serology, generally achieved many years post-treatment. The lack of reliable tests to ensure parasite clearance and to examine the effect of treatment is the main difficulty in evaluating treatment for chronic Chagas disease. Decreases of conventional and non-conventional serological titers can be useful tools to monitor the early impact of treatment. We serially measured changes in antibody levels, including seronegative conversion as well as declines in titers in 53 benznidazole-treated and 89 untreated chronically T. cruzi-infected subjects. Seronegative conversion as well as decreases of titers was significantly higher in treated compared with untreated patients. A strong concordance was found between decreases of titers of conventional and non-conventional serologic tests post-treatment, reaffirming the findings. When seronegative conversion plus decreases of titers were considered altogether, the impact of treatment was higher, in a shorter follow-up period than previously considered. New tools for monitoring the effectiveness of treatment of chronic Chagas disease are necessary, and the results showed in this study is a contribution to researchers and physicians who assist patients suffering from this disease

White Paper and Roadmap for Quantum Gravity Phenomenology in the Multi-Messenger Era

The unification of quantum mechanics and general relativity has long been elusive. Only recently have empirical predictions of various possible theories of quantum gravity been put to test. The dawn of multi-messenger high-energy astrophysics has been tremendously beneficial, as it allows us to study particles with much higher energies and travelling much longer distances than possible in terrestrial experiments, but more progress is needed on several fronts. A thorough appraisal of current strategies and experimental frameworks, regarding quantum gravity phenomenology, is provided here. Our aim is twofold: a description of tentative multimessenger explorations, plus a focus on future detection experiments. As the outlook of the network of researchers that formed through the COST Action CA18108 "Quantum gravity phenomenology in the multi-messenger approach (QG-MM)", in this work we give an overview of the desiderata that future theoretical frameworks, observational facilities, and data-sharing policies should satisfy in order to advance the cause of quantum gravity phenomenology.Comment: Submitted to CQG for the Focus Issue on "Quantum Gravity Phenomenology in the Multi-Messenger Era: Challenges and Perspectives". Please contact us to express interesst of endorsement of this white pape

Inhibitory Receptors Are Expressed by Trypanosoma cruzi-Specific Effector T Cells and in Hearts of Subjects with Chronic Chagas Disease

We had formerly demonstrated that subjects chronically infected with Trypanosoma cruzi show impaired T cell responses closely linked with a process of T cell exhaustion. Recently, the expression of several inhibitory receptors has been associated with T cell dysfunction and exhaustion. In this study, we have examined the expression of the cytotoxic T lymphocyte antigen 4 (CTLA-4) and the leukocyte immunoglobulin like receptor 1 (LIR-1) by peripheral T. cruzi antigen-responsive IFN-gamma (IFN-γ)-producing and total T cells from chronically T. cruzi-infected subjects with different clinical forms of the disease. CTAL-4 expression was also evaluated in heart tissue sections from subjects with severe myocarditis. The majority of IFN-γ-producing CD4+ T cells responsive to a parasite lysate preparation were found to express CTLA-4 but considerably lower frequencies express LIR-1, irrespective of the clinical status of the donor. Conversely, few IFN-γ-producing T cells responsive to tetanus and diphtheria toxoids expressed CTLA-4 and LIR-1. Polyclonal stimulation with anti-CD3 antibodies induced higher frequencies of CD4+CTAL-4+ T cells in patients with severe heart disease than in asymptomatic subjects. Ligation of CTLA-4 and LIR-1 with their agonistic antibodies, in vitro, reduces IFN-γ production. Conversely, CTLA-4 blockade did not improved IFN-γ production in response to T. cruzi antigens. Subjects with chronic T. cruzi infection had increased numbers of CD4+LIR-1+ among total peripheral blood mononuclear cells, relative to uninfected individuals and these numbers decreased after treatment with benznidazole. CTLA-4 was also expressed by CD3+ T lymphocytes infiltrating heart tissues from chronically infected subjects with severe myocarditis. These findings support the conclusion that persistent infection with T. cruzi leads to the upregulation of inhibitory receptors which could alter parasite specific T cell responses in the chronic phase of Chagas disease

A detailed study of the very-high-energy Crab pulsar emission with the LST-1

Context: There are currently three pulsars firmly detected by imaging atmospheric Cherenkov telescopes (IACTs), two of them reaching TeV energies, challenging models of very-high-energy (VHE) emission in pulsars. More precise observations are needed to better characterize pulsar emission at these energies. The LST-1 is the prototype of the Large-Sized Telescope, that will be part of the Cherenkov Telescope Array Observatory (CTAO). Its improved performance over previous IACTs makes it well suited for studying pulsars. Aims: To study the Crab pulsar emission with the LST-1, improving and complementing the results from other telescopes. These observations can also be used to characterize the potential of the LST-1 to study other pulsars and detect new ones. Methods: We analyzed a total of $\sim$103 hours of gamma-ray observations of the Crab pulsar conducted with the LST-1 in the period from September 2020 to January 2023. The observations were carried out at zenith angles less than 50 degrees. A new analysis of the Fermi-LAT data was also performed, including $\sim$14 years of observations. Results: The Crab pulsar phaseogram, long-term light-curve, and phase-resolved spectra are reconstructed with the LST-1 from 20 GeV to 450 GeV for P1 and up to 700 GeV for P2. The pulsed emission is detected with a significance of 15.2$σ$. The two characteristic emission peaks of the Crab pulsar are clearly detected (>10$σ$), as well as the so-called bridge emission (5.7$σ$). We find that both peaks are well described by power laws, with spectral indices of $\sim$3.44 and $\sim$3.03 respectively. The joint analysis of Fermi-LAT and LST-1 data shows a good agreement between both instruments in the overlapping energy range. The detailed results obtained in the first observations of the Crab pulsar with LST-1 show the potential that CTAO will have to study this type of sources

Performance of the joint LST-1 and MAGIC observations evaluated with Crab Nebula data

Aims. Large-Sized Telescope 1 (LST-1), the prototype for the Large-Sized Telescope at the upcoming Cherenkov Telescope Array Observatory, is concluding its commissioning phase at the Observatorio del Roque de los Muchachos on the island of La Palma. The proximity of LST-1 to the two MAGIC (Major Atmospheric Gamma Imaging Cherenkov) telescopes makes it possible to carry out observations of the same gamma-ray events with both systems. Methods. We describe the joint LST-1+MAGIC analysis pipeline and used simultaneous Crab Nebula observations and Monte Carlo simulations to assess the performance of the three-telescope system. The addition of the LST-1 telescope allows for the recovery of events in which one of the MAGIC images is too dim to survive analysis quality cuts. Results. Thanks to the resulting increase in the collection area and stronger background rejection, we found a significant improvement in sensitivity, allowing for the detection of 30% weaker fluxes in the energy range between 200 GeV and 3 TeV. The spectrum of the Crab Nebula, reconstructed in the energy range between ∼60 GeV and ∼10 TeV, is in agreement with previous measurements

Multiwavelength study of the galactic PeVatron candidate LHAASO J2108+5157

Context. Several new ultrahigh-energy (UHE) γ-ray sources have recently been discovered by the Large High Altitude Air Shower Observatory (LHAASO) collaboration. These represent a step forward in the search for the so-called Galactic PeVatrons, the enigmatic sources of the Galactic cosmic rays up to PeV energies. However, it has been shown that multi-TeV γ-ray emission does not necessarily prove the existence of a hadronic accelerator in the source; indeed this emission could also be explained as inverse Compton scattering from electrons in a radiation-dominated environment. A clear distinction between the two major emission mechanisms would only be made possible by taking into account multi-wavelength data and detailed morphology of the source. Aims. We aim to understand the nature of the unidentified source LHAASO J2108+5157, which is one of the few known UHE sources with no very high-energy (VHE) counterpart. Methods. We observed LHAASO J2108+5157 in the X-ray band with XMM-Newton in 2021 for a total of 3.8 hours and at TeV energies with the Large-Sized Telescope prototype (LST-1), yielding 49 hours of good-quality data. In addition, we analyzed 12 years of Fermi-LAT data, to better constrain emission of its high-energy (HE) counterpart 4FGL J2108.0+5155. We used naima and jetset software packages to examine the leptonic and hadronic scenario of the multi-wavelength emission of the source. Results. We found an excess (3.7σ) in the LST-1 data at energies E > 3 TeV. Further analysis of the whole LST-1 energy range, assuming a point-like source, resulted in a hint (2.2σ) of hard emission, which can be described with a single power law with a photon index of Σ = 1.6 ± 0.2 the range of 0.3 - 100 TeV. We did not find any significant extended emission that could be related to a supernova remnant (SNR) or pulsar wind nebula (PWN) in the XMM-Newton data, which puts strong constraints on possible synchrotron emission of relativistic electrons. We revealed a new potential hard source in Fermi-LAT data with a significance of 4σ and a photon index of Σ = 1.9 ± 0.2, which is not spatially correlated with LHAASO J2108+5157, but including it in the source model we were able to improve spectral representation of the HE counterpart 4FGL J2108.0+5155. Conclusions. The LST-1 and LHAASO observations can be explained as inverse Compton-dominated leptonic emission of relativistic electrons with a cutoff energy of 100-30+70 TeV. The low magnetic field in the source imposed by the X-ray upper limits on synchrotron emission is compatible with a hypothesis of a PWN or a TeV halo. Furthermore, the spectral properties of the HE counterpart are consistent with a Geminga-like pulsar, which would be able to power the VHE-UHE emission. Nevertheless, the lack of a pulsar in the neighborhood of the UHE source is a challenge to the PWN/TeV-halo scenario. The UHE γ rays can also be explained as π0 decay-dominated hadronic emission due to interaction of relativistic protons with one of the two known molecular clouds in the direction of the source. Indeed, the hard spectrum in the LST-1 band is compatible with protons escaping a shock around a middle-aged SNR because of their high low-energy cut-off, but the origin of the HE γ-ray emission remains an open question

Observations of the Crab Nebula and Pulsar with the Large-Sized Telescope Prototype of the Cherenkov Telescope Array

CTA (Cherenkov Telescope Array) is the next generation ground-based observatory for gamma-ray astronomy at very-high energies. The Large-Sized Telescope prototype (\LST{}) is located at the Northern site of CTA, on the Canary Island of La Palma. LSTs are designed to provide optimal performance in the lowest part of the energy range covered by CTA, down to $\simeq 20$ GeV. \LST{} started performing astronomical observations in November 2019, during its commissioning phase, and it has been taking data since then. We present the first \LST{} observations of the Crab Nebula, the standard candle of very-high energy gamma-ray astronomy, and use them, together with simulations, to assess the basic performance parameters of the telescope. The data sample consists of around 36 hours of observations at low zenith angles collected between November 2020 and March 2022. \LST{} has reached the expected performance during its commissioning period - only a minor adjustment of the preexisting simulations was needed to match the telescope behavior. The energy threshold at trigger level is estimated to be around 20 GeV, rising to $\simeq 30$ GeV after data analysis. Performance parameters depend strongly on energy, and on the strength of the gamma-ray selection cuts in the analysis: angular resolution ranges from 0.12 to 0.40 degrees, and energy resolution from 15 to 50\%. Flux sensitivity is around 1.1\% of the Crab Nebula flux above 250 GeV for a 50-h observation (12\% for 30 minutes). The spectral energy distribution (in the 0.03 - 30 TeV range) and the light curve obtained for the Crab Nebula agree with previous measurements, considering statistical and systematic uncertainties. A clear periodic signal is also detected from the pulsar at the center of the Nebula.Comment: Submitted to Ap