| 11. |
- Christiansen, J. S., et al.
(författare)
-
Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations
- 2016
-
Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 174:6
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). Participants: A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry. Evidence: Current literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues. Consensus process: Following plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors. Conclusions: LAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations.
|
|
| 12. |
- Mizuki, T., et al.
(författare)
-
Orbital Characterization of GJ1108A System, and Comparison of Dynamical Mass with Model-derived Mass for Resolved Binaries
- 2018
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 865:2
-
Tidskriftsartikel (refereegranskat)abstract
- We report an orbital characterization of GJ1108Aab that is a low-mass binary system in the pre-main-sequence phase. Via the combination of astrometry using adaptive optics and radial velocity measurements, an eccentric orbital solution of e = 0.63 is obtained, which might be induced by the Kozai-Lidov mechanism with a widely separated GJ1108B system. Combined with several observed properties, we confirm that the system is indeed young. Columba is the most probable moving group, to which the GJ1108A system belongs, although its membership to the group has not been established. If the age of Columba is assumed for GJ1108A, the dynamical masses of both GJ1108Aa and GJ1108Ab (M-dynamical,M-GJ1108Aa= 0.72 +/- 0.04 M-circle dot and M-dynamical,M-GJ1108Ab = 0.30 +/- 0.03 M-circle dot) are more massive than what an evolutionary model predicts based on the age and luminosities. We consider that the discrepancy in mass comparison can be attributed to an age uncertainty; the system is likely older than stars in Columba, and effects that are not implemented in classical models such as accretion history and magnetic activity are not preferred to explain the mass discrepancy. We also discuss the performance of the evolutionary model by compiling similar low-mass objects in the evolutionary state based on the literature. Consequently, it is suggested that the current model on average reproduces the mass of resolved low-mass binaries without any significant offsets.
|
|
| 13. |
- Nguyen, Thanh N, et al.
(författare)
-
Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
- 2023
-
Ingår i: Neurology. - 1526-632X. ; 100:4
-
Tidskriftsartikel (refereegranskat)abstract
- Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
|
|
| 14. |
- Allen, D. B., et al.
(författare)
-
GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults
- 2016
-
Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 174:2
-
Tidskriftsartikel (refereegranskat)abstract
- Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement.
|
|
| 15. |
- Lazzoni, C., et al.
(författare)
-
The search for disks or planetary objects around directly imaged companions : a candidate around DH Tauri B
- 2020
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 641
-
Tidskriftsartikel (refereegranskat)abstract
- Context. In recent decades, thousands of substellar companions have been discovered with both indirect and direct methods of detection. While the majority of the sample is populated by objects discovered using radial velocity and transit techniques, an increasing number have been directly imaged. These planets and brown dwarfs are extraordinary sources of information that help in rounding out our understanding of planetary systems.Aims. In this paper, we focus our attention on substellar companions detected with the latter technique, with the primary goal of investigating their close surroundings and looking for additional companions and satellites, as well as disks and rings. Any such discovery would shed light on many unresolved questions, particularly with regard to their possible formation mechanisms.Methods. To reveal bound features of directly imaged companions, whether for point-like or extended sources, we need to suppress the contribution from the source itself. Therefore, we developed a method based on the negative fake companion technique that first estimates the position in the field of view (FoV) and the flux of the imaged companion with high precision, then subtracts a rescaled model point spread function (PSF) from the imaged companion, using either an image of the central star or another PSF in the FoV. Next it performs techniques, such as angular differential imaging, to further remove quasi-static patterns of the star (i.e., speckle contaminants) that affect the residuals of close-in companions.Results. After testing our tools on simulated companions and disks and on systems that were chosen ad hoc, we applied the method to the sample of substellar objects observed with SPHERE during the SHINE GTO survey. Among the 27 planets and brown dwarfs we analyzed, most objects did not show remarkable features, which was as expected, with the possible exception of a point source close to DH Tau B. This candidate companion was detected in four different SPHERE observations, with an estimated mass of ~1MJup, and a mass ratio with respect to the brown dwarf of 1∕10. This binary system, if confirmed, would be the first of its kind, opening up interesting questions for the formation mechanism, evolution, and frequency of such pairs. In order to address the latter, the residuals and contrasts reached for 25 companions in the sample of substellar objects observed with SPHERE were derived. If the DH Tau Bb companion is real, the binary fraction obtained is ~7%, which is in good agreement with the results obtained for field brown dwarfs.Conclusions. While there may currently be many limitations affecting the exploration of bound features to directly imaged exoplanets and brown dwarfs, next-generation instruments from the ground and space (i.e., JWST, ELT, and LUVOIR) will be able to image fainter objects and, thus, drive the application of this technique in upcoming searches for exo-moons and circumplanetary disks.
|
|
| 16. |
- Zurlo, A., et al.
(författare)
-
Orbital and dynamical analysis of the system around HR 8799 New astrometric epochs from VLT/SPHERE and LBT/LUCI
- 2022
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 666
-
Tidskriftsartikel (refereegranskat)abstract
- Context. HR 8799 is a young planetary system composed of four planets and a double debris belt. Being the first multi-planetary system discovered with the direct imaging technique, it has been observed extensively since 1998. This wide baseline of astrometric measurements, counting over 50 observations in 20 years, permits a detailed orbital and dynamical analysis of the system.Aims. To explore the orbital parameters of the planets, their dynamical history, and the planet-to-disk interaction, we made follow-up observations of the system during the VLT/SPHERE guaranteed time observation program. We obtained 21 observations, most of them in favorable conditions. In addition, we observed HR 8799 with the instrument LUCI at the Large Binocular Telescope (LBT).Methods. All the observations were reduced with state-of-the-art algorithms implemented to apply the spectral and angular differential imaging method. We re-reduced the SPHERE data obtained during the commissioning of the instrument and in three open-time programs to have homogeneous astrometry. The precise position of the four planets with respect to the host star was calculated by exploiting the fake negative companions method. We obtained an astrometric precision of the order of 6 mas in the worst case and 1 mas in the best case. To improve the orbital fitting, we also took into account all of the astrometric data available in the literature. From the photometric measurements obtained in different wavelengths, we estimated the masses of the planets following the evolutionary models.Results. We obtained updated parameters for the orbits with the assumption of coplanarity, relatively small eccentricities, and periods very close to the 2:1 resonance. We also refined the dynamical mass of each planet and the parallax of the system (24.49 ± 0.07 mas), which overlap with the recent Gaia eDR3/DR3 estimate. Hydrodynamical simulations suggest that inward migration of the planets caused by the interaction with the disk might be responsible for the planets being locked in resonance. We also conducted detailed N-body simulations indicating possible positions of a putative fifth planet with a mass below the present detection limits of ≃3 MJup.
|
|
| 17. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
-
Growth Hormone Research Society perspective on biomarkers of GH action in children and adults
- 2018
-
Ingår i: Endocrine Connections. - : Bioscientifica. - 2049-3614. ; 7:3
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The Growth Hormone Research Society (GRS) convened a Workshop in 2017 to evaluate clinical endpoints, surrogate endpoints and biomarkers during GH treatment of children and adults and in patients with acromegaly. Participants: GRS invited 34 international experts including clinicians, basic scientists, a regulatory scientist and physicians from the pharmaceutical industry. Evidence: Current literature was reviewed and expert opinion was utilized to establish the state of the art and identify current gaps and unmet needs. Consensus process: Following plenary presentations, breakout groups discussed questions framed by the planning committee. The attendees re-convened after each breakout session to share the group reports. A writing team compiled the breakout session reports into a document that was subsequently discussed and revised by participants. This was edited further and circulated for final review after the meeting. Participants from pharmaceutical companies were not part of the writing process. Conclusions: The clinical endpoint in paediatric GH treatment is adult height with height velocity as a surrogate endpoint. Increased life expectancy is the ideal but unfeasible clinical endpoint of GH treatment in adult GH-deficient patients (GHDA) and in patients with acromegaly. The pragmatic clinical endpoints in GHDA include normalization of body composition and quality of life, whereas symptom relief and reversal of comorbidities are used in acromegaly. Serum IGF-I is widely used as a biomarker, even though it correlates weakly with clinical endpoints in GH treatment, whereas in acromegaly, normalization of IGF-I may be related to improvement in mortality. There is an unmet need for novel biomarkers that capture the pleiotropic actions of GH in relation to GH treatment and in patients with acromegaly.
|
|
| 18. |
- Maire, A-L, et al.
(författare)
-
Hint of curvature in the orbital motion of the exoplanet 51 Eridani b using 3 yr of VLT/SPHERE monitoring
- 2019
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 624
-
Tidskriftsartikel (refereegranskat)abstract
- Context. The 51 Eridani system harbors a complex architecture with its primary star forming a hierarchical system with the binary GJ 3305AB at a projected separation of 2000 au, a giant planet orbiting the primary star at 13 au, and a low-mass debris disk around the primary star with possible cold and warm components inferred from the spectral energy distribution. Aims. We aim to better constrain the orbital parameters of the known giant planet. Methods. We monitored the system over three years from 2015 to 2018 with the Spectro-Polarimetric High-contrast Exoplanet REsearch (SPHERE) instrument at the Very Large Telescope (VET). Results. We measure an orbital motion for the planet of similar to 130 mas with a slightly decreasing separation (similar to 10 mas) and find a hint of curvature. This potential curvature is further supported at 3 sigma significance when including literature Gemini Planet Imager (GPI) astrometry corrected for calibration systematics. Fits of the SPHERE and GPI data using three complementary approaches provide broadly similar results. The data suggest an orbital period of 32(-9)(+17) yr (i.e., 12(-2)(+4), au in semi-major axis), an inclination of 133(-7)(+1)(4) deg, an eccentricity of 0.45(-0.15)(+0.10), and an argument of periastron passage of 87(-30)(+34) deg [mod 180 degrees]. The time at periastron passage and the longitude of node exhibit bimodal distributions because we do not yet detect whether the planet is accelerating or decelerating along its orbit. Given the inclinations of the orbit and of the stellar rotation axis (134-144 degrees), we infer alignment or misalignment within 18 degrees for the star-planet spin-orbit. Further astrometric monitoring in the next 3-4 yr is required to confirm at a higher significance the curvature in the motion of the planet, determine if the planet is accelerating or decelerating on its orbit, and further constrain its orbital parameters and the star-planet spin-orbit.
|
|
| 19. |
- Vigan, A., et al.
(författare)
-
The VLT/NaCo large program to probe the occurrence of exoplanets and brown dwarfs at wide orbits
- 2017
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 603
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding the formation and evolution of giant planets (>= 1 M-Jup) at wide orbital separation (>= 5 AU) is one of the goals of direct imaging. Over the past 15 yr, many surveys have placed strong constraints on the occurrence rate of wide-orbit giants, mostly based on non-detections, but very few have tried to make a direct link with planet formation theories. In the present work, we combine the results of our previously published VLT/NaCo large program with the results of 12 past imaging surveys to constitute a statistical sample of 199 FGK stars within 100 pc, including three stars with sub-stellar companions. Using Monte Carlo simulations and assuming linear flat distributions for the mass and semi-major axis of planets, we estimate the sub-stellar companion frequency to be within 0.75-5.70% at the 68% confidence level (CL) within 20-300 AU and 0.5-75 M-Jup, which is compatible with previously published results. We also compare our results with the predictions of state-of-the-art population synthesis models based on the gravitational instability (GI) formation scenario with and without scattering. We estimate that in both the scattered and non-scattered populations, we would be able to detect more than 30% of companions in the 1-75 M-Jup range (95% CL). With the three sub-stellar detections in our sample, we estimate the fraction of stars that host a planetary system formed by GI to be within 1.0-8.6% (95% CL). We also conclude that even though GI is not common, it predicts a mass distribution of wide-orbit massive companions that is much closer to what is observed than what the core accretion scenario predicts. Finally, we associate the present paper with the release of the Direct Imaging Virtual Archive (DIVA), a public database that aims at gathering the results of past, present, and future direct imaging surveys.
|
|
| 20. |
- Takahashi, Y., et al.
(författare)
-
Weekly somapacitan had no adverse effects on glucose metabolism in adults with growth hormone deficiency
- 2022
-
Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403.
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose The long-term effects of long-acting growth hormone (LAGH) analogues on glucose metabolism in adult growth hormone deficiency (AGHD) are not known. We investigated the impact of LAGH somapacitan, administered once-weekly, on glucose metabolism in patients with AGHD. Methods In post hoc-defined analyses, we compared the effects of somapacitan with daily growth hormone (GH) and placebo on fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-beta) in patients with AGHD across a unique data set from three phase 3 randomized controlled trials (REAL 1, REAL 2 and REAL Japan). Results No new cases of diabetes mellitus were reported with somapacitan. Among GH-naive patients (n = 120 somapacitan, n = 119 daily GH), higher changes from baseline in FPG, HOMA-IR and fasting insulin levels were observed with daily GH versus somapacitan at 34 weeks, but not at 86 weeks. HbA1c and HOMA-beta did not differ between groups at either timepoint. Among treatment-naive patients, sex, age, fasting insulin, glucose tolerance status and body mass index did not influence changes in glucose metabolism. In previously treated patients (REAL 1 extension: n = 51 somapacitan, n = 52 daily GH; REAL 2: n = 61 and n = 31, respectively; REAL Japan: n = 46 and n = 16, respectively), the difference in changes from baseline were not statistically significant between somapacitan and daily GH for any glucose metabolism parameters. Conclusions Somapacitan, compared with daily GH, did not adversely affect glucose metabolism up to 86 weeks in a large cohort of treatment-naive or previously treated patients with AGHD. Trial registrations (date of registration): NCT02229851 (2 September 2014), NCT02382939 (3 March 2015), NCT03075644 (7 March 2017).
|
|
