A

Abstract:  Objective: to assess the adjusted Global Antiphospholipid Syndrome Score (aGAPSS) instrument to estimate the risk of vascular thrombosis in primary antiphospholipid syndrome (pAPS). A retrospective study was done between 2013-2020, including patients with pAPS by Sydney criteria. The presence of arterial and venous thrombosis (tAPS), obstetrical comorbidity (oAPS), non-criteria manifestations (NCM), antiphospholipid antibodies (APLA), recurrent thrombosis and mortality were evaluated. Patients were grouped in tAPS, oAPS or both; the last one was used when the stratification was done. In the first visit, aGAPSS was calculated by adding: arterial hypertension: 1, hyperlipidemia: 3, moderate-high titles of anti-cardiolipin antibody (aCL): 5, anti-β2glicoprotein I (aB2GPI): 4 and lupus anticoagulant (LA): 4. aGAPSS ≥ 10 was considered high. Results: 85 patients entered the study, 74,11% completed the follow-up. 87,1% were women, mean age was 36 years (32,75-40,25), illness of 53 months (25-114). 62,35% had oAPS, 24,5% tAPS and 12,94% both. There were 18 arterial thrombosis, 11 venous thrombosis and 3 in both sites. Patients with tAPS had longer illness (p=0,04), higher rates of aB2GP1 (p=<0,001) and triple positivity (p=0,0003). The mean aGAPSS was 9 (5-12); in tAPS the mean value was 9 (8,75-13) and in oAPS 9 (5-9); p=0,008. There was no difference between patients with criteria manifestations and NCM. New trombosis (12,69%) happened in tAPS; the mean time was 26 months (15-49). There were 4 arterial thrombosis, 2 venous thrombosis and 2 in both sites. The mean aGAPSS in patients with recurrence was 13 (9-13), 62,50% had aGAPSS ≥ 10; and 87% had MNC. 4 (6,34%) patients died, all of them with recurrent thrombosis. aGAPSS ≥ 10 predicted new thrombosis (p=0,016). Patients with recurrence had a worse survival curve (p= 0,00000). Conclusion: assessing the risk of thrombosis in APS with aGAPSS could identify individuals at high risk of recurrence, monitor them, and intervene to prevent future events.Resumen:  Objetivo: valorar el instrumento Global Antiphospholipid Sydrome Score ajustado (aGAPSS) para estimar riesgo de trombosis vascular en SAF primario (SAFP). Se realizó un estudio retrospectivo incluyendo pacientes con SAFP (criterios de Sydney) entre 2013 y 2020 de Hospital Materno-neonatal y Córdoba. Se analizaron: trombosis venosa y arterial (SAFT), morbilidad obstétrica (SAFO), manifestaciones no criterio (MNC), anticuerpos antifosfolípidos (AAF), recurrencia de trombosis y mortalidad. Se agruparon en SAFT, SAFO o ambas; el último grupo se utilizó para estratificación del riesgo. En visita basal calculamos aGAPPS sumando: HTA: 1, dislipemia: 3, anticuerpos anticardiolipinas (ACA) IgM/IgG títulos moderados-altos: 5, anticuerpos antibeta2glicoproteína I (ABGPI): 4 y anticoagulante lúpico (AL): 4. Se consideró aGAPSS alto  ≥ 10. Las variables continuas se expresaron como mediana y rango intercuartil; las categóricas como frecuencia y porcentaje. Se utilizó el test de Fisher para variables categóricas y test de Wilcoxon para variables mensurables. p < 0,05 fueron significativos. Aprobado por CIEIS del Adulto. Resultados: Ingresaron 85 pacientes, 74,11% completaron seguimiento. 87,1% mujeres, mediana de edad 36 años (32,75-40,25). 62,35% presentaban SAFO, 24,5% SAFT y 12,94% ambas. Presentaron 18 trombosis arteriales, 11 venosas y 3 en ambos sitios. Pacientes con SAFT tuvieron mayor duración de enfermedad (p=0,04), mayores tasas de ABGP1 (p=<0,001) y triple positividad (p=0,0003). La mediana del aGAPSS fue de 9 (5-12). En SAFT la mediana fue 9 (8,75-13) y en SAFO 9 (5-9); p=0,008. No hubo diferencia entre pacientes con manifestaciones criterio vs MNC. Las nuevas trombosis 12,69% ocurrieron en SAFT; la mediana del tiempo fue 26 meses (15-49). 4 fueron arteriales, 2 venosas y 2 ambas. La mediana de aGAPSS en pacientes con recurrencia fue 13 (9-13), 62,50% con GAPSS ≥ 10; y 87% presentaron MNC. 4 (6,34 %) pacientes fallecieron, todos con retrombosis. aGAPSS ≥ 10 predijo nuevas trombosis (p=0,016). Los pacientes con retrombosis tuvieron peor curva de sobrevida (p= 0,00000). Conclusión: La valoración del riesgo de trombosis en SAF con aGAPSS permitiría identificar individuos con alto riesgo de recurrencia, monitorizarlos e intervenir para prevenir futuros eventos.

Association of intronic variants of the KCNAB1 gene with lateral temporal epilepsy.

The KCNAB1 gene is a candidate susceptibility factor for lateral temporal epilepsy (LTE) because of its functional interaction with LGI1, the gene responsible for the autosomal dominant form of LTE. We investigated association between polymorphic variants across the KCNAB1 gene and LTE. The allele and genotype frequencies of 14 KCNAB1 intronic SNPs were determined in 142 Italian LTE patients and 104 healthy controls and statistically evaluated. Single SNP analysis revealed one SNP (rs992353) located near the 3'end of KCNAB1 slightly associated with LTE after multiple testing correction (odds ratio=2.25; 95% confidence interval 1.26-4.04; P=0.0058). Haplotype analysis revealed two haplotypes with frequencies higher in cases than in controls, and these differences were statistically significant after permutation tests (Psim=0.047 and 0.034). One of these haplotypes was shown to confer a high risk for the syndrome (odds ratio=12.24; 95% confidence interval 1.32-113.05) by logistic regression analysis. These results support KCNAB1 as a susceptibility gene for LTE, in agreement with previous studies showing that this gene may alter susceptibility to focal epilepsy

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

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

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

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

Star tracking for pointing determination of Imaging Atmospheric Cherenkov Telescopes: Application to the Large-Sized Telescope of the Cherenkov Telescope Array

We present a novel approach to the determination of the pointing of Imaging Atmospheric Cherenkov Telescopes (IACTs) using the trajectories of the stars in their camera s field of view. The method starts with the reconstruction of the star positions from the Cherenkov camera data, taking into account the point spread function of the telescope, to achieve a satisfying reconstruction accuracy of the pointing position. A simultaneous fit of all reconstructed star trajectories is then performed with the orthogonal distance regression (ODR) method. ODR allows us to correctly include the star position uncertainties and use the time as an independent variable. Having the time as an independent variable in the fit makes it better suitable for various star trajectories. This method can be applied to any IACT and requires neither specific hardware nor interface or special data-taking mode. In this paper, we use the Large-Sized Telescope (LST) data to validate it as a useful tool to improve the determination of the pointing direction during regular data taking. The simulation studies show that the accuracy and precision of the method are comparable with the design requirements on the pointing accuracy of the LST (=14''). With the typical LST event acquisition rate of 10 kHz, the method can achieve up to 50 Hz pointing monitoring rate, compared to O(1) Hz achievable with standard techniques. The application of the method to the LST prototype (LST-1) commissioning data shows the stable pointing performance of the telescope

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

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

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