New contributions to algorithms and tools for the analysis of photometric and spectroscopic time-series in exoplanet searches

[eng] The current trend in exoplanet research focuses on the detection and characterisation of Earth-sized planets, and the study of their potential subtle and tenuous atmospheres. The aim of this thesis is the development of tools and simulation codes for the detection and characterisation of exoplanets by means of the indirect methods of radial velocities and transits. The structure of the thesis is two-fold. Firstly, we present a multidimensional extension to the well-known period search GLS code, which we dub MGLS (Multidimensional Generalized Lomb-Scargle periodogram). The analysis of a time-series periodogram of radial velocity data is the usual starting point to seek for periodic signals which then can be associated with the reflex Keplerian motion of a star caused by orbiting exoplanets. In the case of multiplanetary systems such analysis is usually carried out in an iterative fashion, known as prewhitening. This approach can diminish the significance and distort the parameters of periodic signals, and we aim to solve those limitations by introducing a multidimensional approach. Additionally, a robust criterion to determine the number of signals (dimensionality) in a time-series is presented. The new approach is more flexible and enhances the significance of multisignal detections and their multiplicity. It is further better capable to pinpoint the fit parameters and is able to compare models of different dimensionality. The MGLS code has been tested with real multiplanetary systems, showing its excellent performance in detectability. The code is publicly available to the community. The second part addresses the effects of rotationally-induced stellar activity on the photometric and spectroscopic observables. The properties, distribution, and evolution of inhomogeneities on the surface of active stars, such as dark spots and bright faculae, significantly influence the determination of the parameters of an orbiting exoplanet. The chromatic effect they have on transmission spectroscopy, for example, could affect the analysis of data from future space missions such as James Webb Space Telescope (JWST) and Ariel. To quantify and mitigate the effects of those surface phenomena, we developed a fast modelling approach to derive the surface distribution and properties of active regions by modelling simultaneous multi-wavelength time-series observables. We present an upgraded version of the StarSim code, now featuring the capability to solve the inverse problem and derive the properties of the stars and their active regions by modelling time-series data. The multiband photometric inverse problem is both analytically and numerically discussed, as well as a broad analysis of the degeneracies found in the inversion process. As a test case, we analyse a BVRI multiband ground photometry dataset of the exoplanet host star WASP-52. From the results, we further simulated the chromatic contribution of surface phenomena on the observables of its transiting planet. We demonstrate that by using contemporaneous ground-based multiband photometry of an active star, it is possible to reconstruct the parameters and distribution of active regions over time, thus making it feasible to quantify the chromatic effects on the planetary radii measured with transit spectroscopy and mitigate them by about an order of magnitude. The obtained results show it is possible to accurately characterise the heterogeneous stellar surface up to a precision of a few parts in 10^5 and validate the scientific case of space missions like Ariel, designed for exoplanetary transmission spectroscopy.[cat] L'interès actual en la recerca en exoplanetes rau en la detecció de planetes cada cop més petits on els senyals són estadísticament poc significatius, particularment en l'estudi de les seves atmosferes. La tesi té com a objectiu el disseny i desenvolupament d'eines i codis sofisticats per a la detecció i caracterització de les propietats d'exoplanetes mitjançant l'ús de les tècniques de velocitat radial i trànsits, i es compon de dues parts diferenciades: la primera, tracta la generalització d'una eina de detecció de periodicitats molt popular en aquest camp (GLS). S'ha desenvolupat una versió multidimensional, que anomenem MGLS (Multidimensional Generalized Lomb-Scargle periodogram), que permet l'ajust simultani d'un nombre arbitrari de senyals, de manera que millora notablement la detectabilitat de senyals compostos, i evita els problemes derivats del filtratge quan es fa servir el procediment seqüencial, com falsos positius/negatius. Addicionalment es presenta un procediment robust per a la determinació del nombre de senyals (dimensionalitat). La segona part, tracta els efectes de l'activitat estel·lar sobre les mesures de velocitat radial i fotometria. L'activitat magnètica superficial en forma de taques i fàcules constitueix superfícies heterogènies, que amb la rotació de l'estrella, produeixen variacions d'intensitat i cromàtiques en els observables. S'ha desenvolupat un codi ràpid per a la modelització física de l'activitat induïda per rotació de taques, prenent com a base una versió de codi preexistent. En la versió StarSim 2, permet dur a terme el problema invers per determinar l'estat de la superfície més probable donades unes observacions fotomètriques. També es desenvolupa una formulació analítica per al problema invers multibanda i s'analitzen detalladament les degeneracions existents en el problema. L'esquema d'inversió i el codi s'aplica a un conjunt de dades multifiltre (BVRI) de l'estrella WASP-52, i es simulen els efectes cromàtics del model d'activitat ajustat sobre els seus trànsits, com procedir per corregir-los per assolir una precisió d'unes poques parts en cent mil, i per tant validar el cas científic que sustenta la missió Ariel per a l'anàlisi d'atmosferes exoplanetàries per espectroscòpia de transmissió

Effectiveness and safety of anti-CGRP monoclonal antibodies in patients over 65 years: a real-life multicentre analysis of 162 patients

Background Anti-CGRP monoclonal antibodies have shown notable effectiveness and tolerability in migraine patients; however, data on their use in elderly patients is still lacking, as clinical trials have implicit age restrictions and real-world evidence is scarce. In this study, we aimed to describe the safety and effectiveness of erenumab, galcanezumab and fremanezumab in migraine patients over 65 years old in real-life. Methods In this observational real-life study, a retrospective analysis of prospectively collected data from 18 different headache units in Spain was performed. Migraine patients who started treatment with any anti-CGRP monoclonal antibody after the age of 65 years were included. Primary endpoints were reduction in monthly migraine days after 6 months of treatment and the presence of adverse effects. Secondary endpoints were reductions in headache and medication intake frequencies by months 3 and 6, response rates, changes in patient-reported outcomes and reasons for discontinuation. As a subanalysis, reduction in monthly migraine days and proportion of adverse effects were also compared among the three monoclonal antibodies. Results A total of 162 patients were included, median age 68 years (range 65-87), 74.1% women. 42% had dyslipidaemia, 40.3% hypertension, 8% diabetes, and 6.2% previous cardiovascular ischaemic disease. The reduction in monthly migraine days at month 6 was 10.17.3 days. A total of 25.3% of patients presented adverse effects, all of them mild, with only two cases of blood pressure increase. Headache and medication intake frequencies were significantly reduced, and patient-reported outcomes were improved. The proportions of responders were 68%, 57%, 33% and 9% for reductions in monthly migraine days >= 30%,>= 50%,>= 75% and 100%, respectively. A total of 72.8% of patients continued with the treatment after 6 months. The reduction in migraine days was similar for the different anti-CGRP treatments, but fewer adverse effects were detected with fremanezumab (7.7%). Conclusions Anti-CGRP mAbs are safe and effective treatments in migraine patients over 65 years old in real-life clinical practice

Effectiveness and safety of anti-CGRP monoclonal antibodies in patients over 65 years: a real-life multicentre analysis of 162 patients

Abstract Background Anti-CGRP monoclonal antibodies have shown notable effectiveness and tolerability in migraine patients; however, data on their use in elderly patients is still lacking, as clinical trials have implicit age restrictions and real-world evidence is scarce. In this study, we aimed to describe the safety and effectiveness of erenumab, galcanezumab and fremanezumab in migraine patients over 65 years old in real-life. Methods In this observational real-life study, a retrospective analysis of prospectively collected data from 18 different headache units in Spain was performed. Migraine patients who started treatment with any anti-CGRP monoclonal antibody after the age of 65 years were included. Primary endpoints were reduction in monthly migraine days after 6 months of treatment and the presence of adverse effects. Secondary endpoints were reductions in headache and medication intake frequencies by months 3 and 6, response rates, changes in patient-reported outcomes and reasons for discontinuation. As a subanalysis, reduction in monthly migraine days and proportion of adverse effects were also compared among the three monoclonal antibodies. Results A total of 162 patients were included, median age 68 years (range 65–87), 74.1% women. 42% had dyslipidaemia, 40.3% hypertension, 8% diabetes, and 6.2% previous cardiovascular ischaemic disease. The reduction in monthly migraine days at month 6 was 10.1 ± 7.3 days. A total of 25.3% of patients presented adverse effects, all of them mild, with only two cases of blood pressure increase. Headache and medication intake frequencies were significantly reduced, and patient-reported outcomes were improved. The proportions of responders were 68%, 57%, 33% and 9% for reductions in monthly migraine days ≥ 30%, ≥ 50%, ≥ 75% and 100%, respectively. A total of 72.8% of patients continued with the treatment after 6 months. The reduction in migraine days was similar for the different anti-CGRP treatments, but fewer adverse effects were detected with fremanezumab (7.7%). Conclusions Anti-CGRP mAbs are safe and effective treatments in migraine patients over 65 years old in real-life clinical practice. Graphical Abstrac