A novel approach to simulate gene-environment interactions in complex diseases

Background: Complex diseases are multifactorial traits caused by both genetic and environmental factors. They represent the major part of human diseases and include those with largest prevalence and mortality (cancer, heart disease, obesity, etc.). Despite a large amount of information that has been collected about both genetic and environmental risk factors, there are few examples of studies on their interactions in epidemiological literature. One reason can be the incomplete knowledge of the power of statistical methods designed to search for risk factors and their interactions in these data sets. An improvement in this direction would lead to a better understanding and description of gene-environment interactions. To this aim, a possible strategy is to challenge the different statistical methods against data sets where the underlying phenomenon is completely known and fully controllable, for example simulated ones. Results: We present a mathematical approach that models gene-environment interactions. By this method it is possible to generate simulated populations having gene-environment interactions of any form, involving any number of genetic and environmental factors and also allowing non-linear interactions as epistasis. In particular, we implemented a simple version of this model in a Gene-Environment iNteraction Simulator (GENS), a tool designed to simulate case-control data sets where a one gene-one environment interaction influences the disease risk. The main aim has been to allow the input of population characteristics by using standard epidemiological measures and to implement constraints to make the simulator behaviour biologically meaningful. Conclusions: By the multi-logistic model implemented in GENS it is possible to simulate case-control samples of complex disease where gene-environment interactions influence the disease risk. The user has full control of the main characteristics of the simulated population and a Monte Carlo process allows random variability. A knowledge-based approach reduces the complexity of the mathematical model by using reasonable biological constraints and makes the simulation more understandable in biological terms. Simulated data sets can be used for the assessment of novel statistical methods or for the evaluation of the statistical power when designing a study

FLUXNET-CH₄ synthesis activity: objectives, observations, and future directions

We describe a new coordination activity and initial results for a global synthesis of eddy covariance CH4 flux measurements

The Fermi-LAT Light Curve Repository

The Fermi Large Area Telescope (LAT) light curve repository (LCR) is a publicly available, continually updated library of gamma-ray light curves of variable Fermi-LAT sources generated over multiple timescales. The Fermi-LAT LCR aims to provide publication-quality light curves binned on timescales of 3 days, 7 days, and 30 days for 1525 sources deemed variable in the source catalog of the first 10 years of Fermi-LAT observations. The repository consists of light curves generated through full likelihood analyses that model the sources and the surrounding region, providing fluxes and photon indices for each time bin. The LCR is intended as a resource for the time-domain and multi-messenger communities by allowing users to quickly search LAT data to identify correlated variability and flaring emission episodes from gamma-ray sources. We describe the sample selection and analysis employed by the LCR and provide an overview of the associated data access portal.Comment: Accepted for publication in ApJ Supplement Serie

GRB 221009A observations with LST-1 at VHE gamma rays

On October 9th, 2022, the brightest gamma-ray burst (GRB) since the first GRB observation in the late sixties was detected by the Fermi-GBM and Swift-BAT telescopes (GRB 221009A). The outstanding characteristics of this GRB triggered extensive follow-up observations of the source across all wavebands, including at very-high-energy (VHE) gamma rays with the Large-Sized Telescope prototype (LST-1) of the upcoming Cherenkov Telescope Array Observatory (CTAO). In this contribution, we present the analysis and results of the LST-1 observation campaign in October 2022, focusing on the data taken under nominal observing conditions and above 200 GeV

A new method of reconstructing images of gamma-ray telescopes applied to the LST-1 of CTAO

Context. Imaging atmospheric Cherenkov telescopes (IACTs) are used to observe very high-energy photons from the ground. Gamma rays are indirectly detected through the Cherenkov light emitted by the air showers they induce. The new generation of experiments, in particular the Cherenkov Telescope Array Observatory (CTAO), sets ambitious goals for discoveries of new gamma-ray sources and precise measurements of the already discovered ones. To achieve these goals, both hardware and data analysis must employ cutting-edge techniques. This also applies to the LST-1, the first IACT built for the CTAO, which is currently taking data on the Canary island of La Palma. Aims. This paper introduces a new event reconstruction technique for IACT data, aiming to improve the image reconstruction quality and the discrimination between the signal and the background from misidentified hadrons and electrons. Methods. The technique models the development of the extensive air shower signal, recorded as a waveform per pixel, seen by CTAO telescopes’ cameras. Model parameters are subsequently passed to random forest regressors and classifiers to extract information on the primary particle. Results. The new reconstruction was applied to simulated data and to data from observations of the Crab Nebula performed by the LST-1. The event reconstruction method presented here shows promising performance improvements. The angular and energy resolution, and the sensitivity, are improved by 10 to 20% over most of the energy range. At low energy, improvements reach up to 22%, 47%, and 50%, respectively. A future extension of the method to stereoscopic analysis for telescope arrays will be the next important step

Detection of the Geminga pulsar at energies down to 20 GeV with the LST-1 of CTAO

Context. Geminga is the third gamma-ray pulsar firmly detected by imaging atmospheric Cherenkov telescopes (IACTs) after the Crab and the Vela pulsars. Most of its emission is expected at tens of giga-electronvolts, and, out of the planned telescopes of the upcoming Cherenkov Telescope Array Observatory (CTAO), the Large-Sized Telescopes (LSTs) are the only ones with optimised sensitivity at these energies. Aims. We aim to characterise the gamma-ray pulse shape and spectrum of Geminga as observed by the first LST (hereafter LST-1) of the Northern Array of CTAO. Furthermore, this study confirms the great performance and the improved energy threshold of the telescope, as low as 10 GeV for pulsar analysis, with respect to current-generation Cherenkov telescopes. Methods. We analysed 60 hours of good-quality data taken by the LST-1 between December 2022 and March 2024 at zenith angles below 50◦. Additionally, a new Fermi-LAT analysis of 16.6 years of data was carried out to extend the spectral analysis down to 100 MeV. Lastly, a detailed study of the systematic effects was performed. Results. We report the detection of Geminga in the energy range between 20 and 65 GeV. Of the two peaks of the phaseogram, the second one, P2, is detected with a significance of 12.2σ, while the first (P1) reaches a significance level of 2.6σ. The best-fit model for the spectrum of P2 was found to be a power law with a spectral index of Γ = (4.5±0.4stat)−+0062syssys, compatible with the previous results obtained by the MAGIC Collaboration. No evidence of curvature is found in the LST-1 energy range. The joint fit with Fermi-LAT data confirms a preference for a sub-exponential cut-off over a pure exponential, even though both models fail to reproduce the data above several tens of giga-electronvolts. The overall results presented in this paper prove that the LST-1 is an excellent telescope for the observation of pulsars, and improved sensitivity is expected to be achieved with the full CTAO Northern Array

Detection of RS Oph with LST-1 and modelling of its HE/VHE gamma-ray emission

Context. The recurrent nova RS Ophiuchi (RS Oph) underwent a thermonuclear eruption in August 2021. In this event, RS Oph was detected by the High Energy Stereoscopic System (H.E.S.S.), the Major Atmospheric Gamma Imaging Cherenkov (MAGIC), and the first Large-Sized Telescope (LST-1) of the future Cherenkov Telescope Array Observatory (CTAO) at very-high gamma-ray energies above 100 GeV. This means that novae are a new class of very-high-energy (VHE) gamma-ray emitters. Aims. We report the analysis of the RS Oph observations with LST-1. We constrain the particle population that causes the observed emission in hadronic and leptonic scenarios. Additionally, we study the prospects of detecting further novae using LST-1 and the upcoming LST array of CTAO-North. Methods. We conducted target-of-opportunity observations with LST-1 from the first day of this nova event. The data were analysed in the framework of cta-lstchain and Gammapy, the official CTAO-LST reconstruction and analysis packages. One-zone hadronic and leptonic models were considered to model the gamma-ray emission of RS Oph using the spectral information from Fermi-LAT and LST-1, together with public data from the MAGIC and H.E.S.S. telescopes. Results. RS Oph was detected at 6.6σ with LST-1 in the first 6.35 hours of observations following the eruption. The hadronic scenario is preferred over the leptonic scenario considering a proton energy spectrum with a power-law model with an exponential cutoff whose position increases from (0.26 ± 0.08) TeV on day 1 up to (1.6 ± 0.6) TeV on day 4 after the eruption. The deep sensitivity and low energy threshold of the LST-1/LST array will allow us to detect faint novae and increase their discovery rate

Fermi-GBM Discovery of GRB 221009A: An Extraordinarily Bright GRB from Onset to Afterglow

We report the discovery of GRB 221009A, the highest flux gamma-ray burst ever observed by the Fermi Gamma-ray Burst Monitor (GBM). This GRB has continuous prompt emission lasting more than 600 seconds which smoothly transitions to afterglow visible in the GBM energy range (8 keV--40 MeV), and total energetics higher than any other burst in the GBM sample. By using a variety of new and existing analysis techniques we probe the spectral and temporal evolution of GRB 221009A. We find no emission prior to the GBM trigger time (t0; 2022 October 9 at 13:16:59.99 UTC), indicating that this is the time of prompt emission onset. The triggering pulse exhibits distinct spectral and temporal properties suggestive of the thermal, photospheric emission of shock-breakout, with significant emission up to ∼15 MeV. We characterize the onset of external shock at t0+600 s and find evidence of a plateau region in the early-afterglow phase which transitions to a slope consistent with Swift-XRT afterglow measurements. We place the total energetics of GRB 221009A in context with the rest of the GBM sample and find that this GRB has the highest total isotropic-equivalent energy (Eγ,iso=1.0×10^55 erg) and second highest isotropic-equivalent luminosity (Lγ,iso=9.9×10^53 erg/s) based on redshift of z = 0.151. These extreme energetics are what allowed us to observe the continuously emitting central engine of GBM from the beginning of the prompt emission phase through the onset of early afterglow

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

The Cherenkov Telescope Array (CTA) is a next-generation ground-based observatory for gamma-ray astronomy at very high energies. The Large-Sized Telescope prototype (LST-1) is located at the CTA-North site, 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 ≃20 GeV. LST-1 started performing astronomical observations in 2019 November, during its commissioning phase, and it has been taking data ever since. We present the first LST-1 observations of the Crab Nebula, the standard candle of very-high-energy gamma-ray astronomy, and use them, together with simulations, to assess the performance of the telescope. LST-1 has reached the expected performance during its commissioning period—only a minor adjustment of the preexisting simulations was needed to match the telescope’s behavior. The energy threshold at trigger level is around 20 GeV, rising to ≃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.°12-0.°40, and energy resolution from 15%-50%. Flux sensitivity is around 1.1% of the Crab Nebula flux above 250 GeV for a 50 hr 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