Cord cross-sectional area at foramen magnum as a correlate of disability in amyotrophic lateral sclerosis

Spinal cord atrophy is one of the hallmarks of amyotrophic lateral sclerosis (ALS); however, it is not routinely assessed in routine clinical practice. In the present study, we evaluated whether spinal cord cross-sectional area measured at the foramen magnum level using a magnetic resonance imaging head scan represents a clinically meaningful measure to be added to the whole-brain volume assessment. Using an active surface approach, we measured the cord area at the foramen magnum and brain parenchymal fraction on T1-weighted three-dimensional spoiled gradient recalled head scans in two groups of subjects: 23 patients with ALS (males/females, 13/10; mean\u2009\ub1\u2009standard deviation [SD] age 61.7\u2009\ub1\u200910.3 years; median ALS Functional Rating Scale-Revised score 39, range 27-46) and 18 age- and sex-matched healthy volunteers (mean\u2009\ub1\u2009SD age 55.7\u2009\ub1\u200910.2 years). Spinal cord area at the foramen magnum was significantly less in patients than in control subjects and was significantly correlated with disability as measured with the ALS Functional Rating Scale-Revised (\u3c1\u2009=\u20090.593, p\u2009<\u2009 0.005). This correlation remained significant after taking into account inter-individual differences in brain parenchymal fraction (\u3c1\u2009=\u20090.684, p\u2009<\u2009 0.001). Our data show that spinal cord area at the foramen magnum correlates with disability in ALS independently of whole-brain atrophy, thus indicating its potential as a disease biomarker

X-ray and ultraviolet emission of the young planet-hosting star V1298 Tau from coordinated observations with XMM-Newton and Hubble Space Telescope

Atmospheric mass loss plays a major role in the evolution of exoplanets. This process is driven by the stellar high-energy irradiation, especially in the first hundreds of millions of years after dissipation of the proto-planetary disk. A major source of uncertainty in modeling atmospheric photoevaporation and photochemistry is due to the lack of direct measurements of the stellar flux at extreme-UV (EUV) wavelengths. Several empirical relationships have been proposed in the past to link EUV fluxes to emission levels in X-rays, but the stellar samples employed for this aim are heterogeneous, and the available scaling laws provide significantly different predictions, especially for very active stars. We present new far-UV and X-ray observations of V1298 Tau with Hubble Space Telescope/Cosmic Origins Spectrograph and XMM-Newton, aimed to determine more accurately the high-energy emission of this solar-mass pre-main-sequence star, which hosts four exoplanets. Spectroscopic data were employed to derive the plasma emission measure distribution versus temperature, from the chromosphere to the corona, and the possible variability of this irradiation on short and year-long timescales, due to magnetic activity. As a side result, we have also measured the chemical abundances of several elements in the outer atmosphere of V1298 Tau. We employ our results as a new benchmark point for the calibration of the X-ray to EUV scaling laws, and hence to predict the time evolution of the irradiation in the EUV band, and its effect on the evaporation of exo-atmospheres

Photometric follow-up of the 20 Myr-old multi-planet host star V1298~Tau with CHEOPS and ground-based telescopes

V1298 Tau hosts at least four planets. Since its discovery, this system has been a target of intensive photometric and spectroscopic monitoring. The characterisation of its architecture and planets' fundamental properties turned out to be very challenging so far. The determination of the orbital ephemeris of the outermost planet V1298 Tau $e$ remains an open question. Only two transits have been detected so far by $Kepler/K2$ and TESS, allowing for a grid of reference periods to be tested with new observations, without excluding the possibility of transit timing variations. Observing a third transit would allow to better constrain the orbital period, and would also help determining an accurate radius of V1298 Tau $e$ because the former transits showed different depths. We observed V1298 Tau with the CHEOPS space telescope to search for a third transit of planet $e$ within observing windows that have been selected in order to test three of the shortest predicted orbital periods. We also collected ground-based observations to verify the result found with CHEOPS. We reanalysed $Kepler/K2$ and TESS light curves to test how the results derived from these data are affected by alternative photometric extraction and detrending methods. We report the detection with CHEOPS of a transit that could be attributed to V1298 Tau $e$. If so, that result implies that the orbital period calculated from fitting a linear ephemeris to the three available transits is close to $\sim45$ days. Results from the ground-based follow-up marginally support this possibility. We found that $\textit{i}$) the transit observed by CHEOPS has a longer duration compared to that of the transits observed by $Kepler/K2$ and TESS; $\textit{ii}$) the transit observed by TESS is $>30\%$ deeper than that of $Kepler/K2$ and CHEOPS, and deeper than the measurement previously reported in the literature, according to our reanalysis.Comment: Accepted for publication on A&A. The abstract has been edited to fulfill the arXiv requirement

The GAPS programme at TNG. XLVI. Deep search for low-mass planets in late-dwarf systems hosting cold Jupiters

Context. With the growth of comparative exoplanetology, it is increasingly clear that the relationship between inner and outer planets plays a key role in unveiling the mechanisms governing formation and evolution models. For this reason, it is important to probe the inner region of systems hosting long-period giants in search of undetected lower mass planetary companions. Aims: We aim to present the results of a high-cadence and high-precision radial velocity (RV) monitoring of three late-type dwarf stars hosting long-period giants with well-measured orbits in order to search for short-period sub-Neptunes (SN, M sin i < 30 M⊕). Methods: Building on the results and expertise of our previous studies, we carried out combined fits of our HARPS-N data with literature RVs. We used Markov chain Monte Carlo (MCMC) analyses to refine the literature orbital solutions and search for additional inner planets, applying Gaussian process regression techniques to deal with the stellar activity signals where required. We then used the results of our survey to estimate the frequency of sub-Neptunes in systems hosting cold Jupiters, f(SN|CJ), and compared it with the frequency around field M dwarfs, f(SN). Results: We identify a new short-period, low-mass planet orbiting GJ 328, GJ 328 c, with Pc = 241.8-1.7+1.3 days and Mc sin i = 21.4-3.2+3.4M⊕. We moreover identify and model the chromospheric activity signals and rotation periods of GJ 649 and GJ 849, around which no additional planet is found. Then, taking into account also planetary system around the previously analysed low-mass star BD-11 4672, we derive an estimate of the frequencies of inner planets in such systems. In particular, f(SN|CJ) = 0.25-0.07+0.58 for mini-Neptunes (10 M⊕ < M sin i < 30 M⊕, P < 150 d), marginally larger than f(SN). For lower mass planets (M sin i < 10 M⊕) instead f(SN|CJ) < 0.69, which is compatible with f(SN). Conclusions: In light of the newly detected mini-Neptune, we find tentative evidence of a positive correlation between the presence of long-period giant planets and that of inner low-mass planets, f(SN|CJ) > f(SN). This might indicate that cold Jupiters have an opposite influence in the formation of inner sub-Neptunes around late-type dwarfs as opposed to their solar-type counterparts, boosting the formation of mini-Neptunes instead of impeding it

Photometric follow-up of the 20 Myr old multi-planet host star V1298 Tau with CHEOPS and ground-based telescopes

Context. The 20 Myr old star V1298 Tau hosts at least four planets. Since its discovery, this system has been a target of intensive photometric and spectroscopic monitoring. To date, the characterisation of its architecture and planets' fundamental properties has been very challenging. Aims: The determination of the orbital ephemeris of the outermost planet V1298 Tau e remains an open question. Only two transits have been detected so far by Kepler/K2 and TESS, allowing for a grid of reference periods to be tested with new observations, without excluding the possibility of transit timing variations. Observing a third transit would allow for better constraints to be set on the orbital period and would also help in determining an accurate radius for V1298 Tau e because the previous transits showed different depths. Methods: We observed V1298 Tau with the CHaracterising ExOPlanet Satellite (CHEOPS) to search for a third transit of planet e within observing windows selected to test three of the shortest predicted orbital periods. We also collected ground-based observations to verify the result found with CHEOPS. We reanalysed Kepler/K2 and TESS light curves to test how the results derived from these data are affected by alternative photometric extraction and detrending methods. Results: We report the CHEOPS detection of a transit-like signal that could be attributed to V1298 Tau e. If so, that result would imply that the orbital period calculated from fitting a linear ephemeris to the three available transits is close to ~45 days. Results from the ground-based follow-up marginally support this possibility. We found that i) the transit observed by CHEOPS has a longer duration compared to that of the transits observed by Kepler/K2 and TESS; and ii) the transit observed by TESS is >30% deeper than that of Kepler/K2 and CHEOPS, and it is also deeper than the measurement previously reported in the literature, according to our reanalysis. Conclusions: If the new transit detected by CHEOPS is found to be due to V1298 Tau e, this would imply that the planet experiences TTVs of a few hours, as deduced from three transits, as well as orbital precession, which would explain the longer duration of the transit compared to the Kepler/K2 and TESS signals. Another and a priori less likely possibility is that the newly detected transit belongs to a fifth planet with a longer orbital period than that of V1298 Tau e. Planning further photometric follow-up to search for additional transits is indeed necessary to solve the conundrum, as well as to pin down the radius of V1298 Tau e

The GAPS Programme at TNG : XLVII. A conundrum resolved: HIP 66074b/Gaia-3b characterised as a massive giant planet on a quasi-face-on and extremely elongated orbit

The nearby mid-K dwarf HIP 66074 was recently identified as host to a candidate super-Jupiter companion on a similar to 300 day, almost edge-on, orbit, based on Gaia Data Release 3 (DR3) astrometry. Initial attempts at confirming the planetary nature of the signal based on publicly available radial-velocity (RV) observations uncovered an intriguing conundrum: the inferred RV semi-amplitude appears to be a factor of 15 smaller than the one predicted based on the Gaia solution (corresponding to a 7-M-Jup companion on a close to edge-on orbit). We present the results of intensive RV monitoring of HIP 66074 with the HARPS-N spectrograph. We detected the companion at the Gaia period, but with an extremely eccentric orbit (e = 0:948 +/- 0:004), a semi-amplitude K = 93.9(-7.0)(+9.4) m s(-1), and a minimum mass mb sin i(b) = 0.79 +/- 0.05 M-Jup. We used detailed simulations of Gaia astrometry with the DR3 time-span to show that the conundrum can be fully resolved by taking into account the combination of the initially sub-optimal RV sampling and systematic biases in the Gaia astrometric solution, which include an underestimation of the eccentricity and incorrect identification of orbital inclination, which has turned out to correspond to a close to face-on configuration (i less than or similar to 13 degrees). With an estimated mass in the approximate range of 3-7 M-Jup, we find that HIP 66074b (equivalent to Gaia-3b) is the first exoplanet candidate astrometrically detected by Gaia to be successfully confirmed based on RV follow-up observations

The ultra-hot-Jupiter KELT-16 b: Dynamical Evolution and Atmospheric Properties

Abstract We present broad-band photometry of 30 planetary transits of the ultra-hot Jupiter KELT-16 b, using five medium-class telescopes. The transits were monitored through standard B, V, R, I filters and four were simultaneously observed from different places, for a total of 36 new light curves. We used these new photometric data and those from the TESS space telescope to review the main physical properties of the KELT-16 planetary system. Our results agree with previous measurements but are more precise. We estimated the mid-transit times for each of these transits and combined them with others from the literature to obtain 69 epochs, with a time baseline extending over more than four years, and searched for transit time variations. We found no evidence for a period change, suggesting a lower limit for orbital decay at 8 Myr, with a lower limit on the reduced tidal quality factor of Q^{\prime }_{\star }&gt;(1.9 \pm 0.8) \times 10^5 with $95\%$ confidence. We built up an observational, low-resolution transmission spectrum of the planet, finding evidence of the presence of optical absorbers, although with a low significance. Using TESS data, we reconstructed the phase curve finding that KELT-16 b has a phase offset of 25.25 ± 14.03 ○E, a day- and night-side brightness temperature of 3190 ± 61 K and 2668 ± 56 K, respectively. Finally, we compared the flux ratio of the planet over its star at the TESS and Spitzer wavelengths with theoretical emission spectra, finding evidence of a temperature inversion in the planet’s atmosphere, the chemical composition of which is preferably oxygen-rich rather than carbon-rich.</jats:p

Rapamycin treatment for amyotrophic lateral sclerosis protocol for a phase II randomized, double-blind, placebo-controlled, multicenter, clinical trial (RAP-ALS trial)

Introduction: Misfolded aggregated proteins and neuroinflammation significantly contribute to amyotrophic lateral sclerosis (ALS) pathogenesis, hence representing therapeutic targets to modify disease expression. Rapamycin inhibits mechanistic target of Rapamycin (mTOR) pathway and enhances autophagy with demonstrated beneficial effects in neurodegeneration in cell line and animal models, improving phenotype in SQSTM1 zebrafish, in Drosophila model of ALS-TDP, and in the TDP43 mouse model, in which it reduced neuronal loss and TDP43 inclusions. Rapamycin also expands regulatory T lymphocytes (Treg) and increased Treg levels are associated with slow progression in ALS patients. Therefore, we planned a randomized clinical trial testing Rapamycin treatment in ALS patients. Methods: RAP-ALS is a phase II randomized, double-blind, placebo-controlled, multicenter (8 ALS centers in Italy), clinical trial. The primary aim is to assess whether Rapamycin administration increases Tregs number in treated patients compared with control arm. Secondary aims include the assessment of safety and tolerability of Rapamycin in patients with ALS; the minimum dosage to have Rapamycin in cerebrospinal fluid; changes in immunological (activation and homing of T, B, NK cell subpopulations) and inflammatory markers, and on mTOR downstream pathway (S6RP phosphorylation); clinical activity (ALS Functional Rating Scale-Revised, survival, forced vital capacity); and quality of life (ALSAQ40 scale). Discussion: Rapamycin potentially targets mechanisms at play in ALS (i.e., autophagy and neuroinflammation), with promising preclinical studies. It is an already approved drug, with known pharmacokinetics, already available and therefore with significant possibility of rapid translation to daily clinics. Findings will provide reliable data for further potential trials. Ethics and dissemination: The study protocol was approved by the Ethics Committee of Azienda Ospedaliero Universitaria of Modena and by the Ethics Committees of participating centers (Eudract n. 2016-002399-28) based on the Helsinki declaration

VizieR Online Data Catalog: HAT-P-3b and TrES-3b light curves and Mid-times (Ricci+, 2017)

Tables contain the light curves and the calculated Mid-times. (15 data files)

The GAPS programme at TNG XLIX. TOI-5398, the youngest compact multi-planet system composed of an inner sub-Neptune and an outer warm Saturn

Short-period giant planets are frequently found to be solitary compared to other classes of exoplanets. Small inner companions to giant planets with $P \lesssim$ 15 days are known only in five compact systems: WASP-47, Kepler-730, WASP-132, TOI-1130, and TOI-2000. Here, we report the confirmation of TOI-5398, the youngest compact multi-planet system composed of a hot sub-Neptune (TOI-5398 c, $P_{\rm c}$ = 4.77271 days) orbiting interior to a short-period Saturn (TOI-5398 b, $P_{\rm b}$ = 10.590547 days) planet, both transiting around a 650 $\pm$ 150 Myr G-type star. As part of the GAPS Young Object project, we confirmed and characterised this compact system, measuring the radius and mass of both planets, thus constraining their bulk composition. Using multidimensional Gaussian processes, we simultaneously modelled stellar activity and planetary signals from TESS Sector 48 light curve and our HARPS-N radial velocity time series. We have confirmed the planetary nature of both planets, TOI-5398 b and TOI-5398 c, alongside a precise estimation of stellar parameters. Through the use of astrometric, photometric, and spectroscopic observations, our findings indicate that TOI-5398 is a young, active G dwarf star (650 $\pm$ 150 Myr), with a rotational period of $P_{\rm rot}$ = 7.34 days. The transit photometry and radial velocity measurements enabled us to measure both the radius and mass of planets b, $R_b = 10.30\pm0.40 R_{\oplus}$, $M_b = 58.7\pm5.7 M_{\oplus}$, and c, $R_c = 3.52 \pm 0.19 R_{\oplus}$, $M_c = 11.8\pm4.8 M_{\oplus}$. TESS observed TOI-5398 during sector 48 and no further observations are planned in the current Extended Mission, making our ground-based light curves crucial for ephemeris improvement. With a Transmission Spectroscopy Metric value of around 300, TOI-5398 b is the most amenable warm giant (10 < $P$ < 100 days) for JWST atmospheric characterisation.Comment: 29 pages, Paper accepted for publication in Astronomy & Astrophysic