Abstract
Graves’ hyperthyroidism is characterized by the presence of autoantibodies that stimulate the thyroid-stimulating hormone receptor (TSHR), resulting in uncontrolled secretion of excessive ...thyroid hormone. Conventional treatments, including antithyroid medication, radioiodine, or surgery have remained largely unchanged for the past 70 years and either lack efficacy for many patients, or result in lifelong thyroid hormone replacement therapy, in the case of the latter 2 options. The demand for new therapeutic options, combined with greater insight into basic immunobiology, has led to the emergence of novel approaches to treat Graves’ hyperthyroidism. The current therapies under investigation include biologics, small molecules, and peptide immunomodulation. There is a growing focus on TSHR-specific treatment modalities, which carry the advantage of eliciting a specific, targeted approach, with the aim of avoiding disruption of the functioning immune system. These therapies present a new opportunity to supersede the inadequate treatments currently available for some Graves’ patients, offering hope of successful restoration of euthyroidism without the need for ongoing therapy. Several of these therapeutic options have the potential to translate into clinical practice in the near future. This review provides a comprehensive summary of the recent advances and various stages of development of the novel therapeutic approaches to treat Graves’ hyperthyroidism.
Graphical Abstract
Graphical Abstract
Milk is widely fortified, but in the UK only infant formula milk and margarine have statutory vitamin D supplementation (1-2.5 μg (40-100 IU) per 100 kCal and 8 μg (320 IU) per 100 g, ...respectively). ...the typical UK diet, and that of many other countries, is profoundly lacking in vitamin D. A low dietary vitamin D intake, combined with the lack of skin synthesis for half of the year, is reflected in the disturbingly high prevalence of vitamin D insufficiency across the UK. 3 5 How can vitamin D deficiency and insufficiency be determined?
We investigate the interaction between an eccentric planet and a less massive external debris disc. This scenario could occur after planet–planet scattering or merging events. We characterize the ...evolution over a wide range of initial conditions, using a suite of n-body integrations combined with theory. Planets near the disc mid-plane remove the inner debris region, and surviving particles form an eccentric disc apsidally aligned with the planet. The inner disc edge is elliptical and lies just beyond the planet's orbit. Moderately inclined planets (i
plt ≳ 20° for e
plt = 0.8) may instead sculpt debris into a bell-shaped structure enveloping the planet's orbit. Finally, some highly inclined planets (i
plt ∼ 90°) can maintain a disc orthogonal to the planet's plane. In all cases, disc particles undergo rapid evolution, whilst the overall structures evolve more slowly. The shapes of these structures and their density profiles are characterized. The width of the chaotic zone around the planet's orbit is derived in the coplanar case using eccentric Hill radius arguments. This zone is cleared within approximately 10 secular or diffusion times (whichever is longer), and debris assumes its final shape within a few secular times. We quantify the planet's migration and show that it will almost always be small in this mass regime. Our results may be used to characterize unseen eccentric planets using observed debris features.
ABSTRACT
In 2006, Vega was discovered to display excess near-infrared (NIR) emission. Surveys now detect this phenomenon for one fifth of main-sequence stars, across various spectral types and ages. ...The excesses are interpreted as populations of small, hot dust grains very close to their stars, which must originate from comets or asteroids. However, the presence of such grains in copious amounts is mysterious, since they should rapidly sublimate or be blown out of the system. Here, we investigate a potential mechanism to generate excesses: dust migrating inwards under radiation forces sublimates near the star, releasing modest quantities of gas that then traps subsequent grains. This mechanism requires neither specialized system architectures nor high dust supply rates, and could operate across diverse stellar types and ages. The model naturally reproduces many features of inferred dust populations, in particular their location, preference for small grains, steep size distribution, and dust location scaling with stellar luminosity. For Sun-like stars, the mechanism can produce ${2.2 \; \mu {\rm m}}$ excesses that are an order of magnitude larger than those at ${8.5 \; \mu {\rm m}}$, as required by observations. However, for A-type stars the simulated NIR excesses were only twice those in the mid-infrared; grains would have to be 5–10 times smaller than those trapped in our model to be able to explain observed NIR excesses around A stars. Further progress with any hot dust explanation for A stars requires a means for grains to become very hot without either rapidly sublimating or being blown out of the system.
ABSTRACT
Extrasolar debris discs are detected by observing dust, which is thought to be released during planetesimal collisions. This implies that planetesimals are dynamically excited (‘stirred’), ...such that collisions are sufficiently common and violent. The most frequently considered stirring mechanisms are self-stirring by disc self-gravity, and planet-stirring via secular interactions. However, these models face problems when considering disc mass, self-gravity, and planet eccentricity, leading to the possibility that other, unexplored mechanisms instead stir debris. We hypothesize that planet-stirring could be more efficient than the traditional secular model implies, due to two additional mechanisms. First, a planet at the inner edge of a debris disc can scatter massive bodies on to eccentric, disc-crossing orbits, which then excite debris (‘projectile stirring’). Second, a planet can stir debris over a wide region via broad mean-motion resonances, both at and between nominal resonance locations (‘resonant stirring’). Both mechanisms can be effective even for low-eccentricity planets, unlike secular-planet-stirring. We run N-body simulations across a broad parameter space, to determine the viability of these new stirring mechanisms. We quantify stirring levels using a bespoke program for assessing rebound debris simulations, which we make publicly available. We find that even low-mass projectiles can stir discs, and verify this with a simple analytic criterion. We also show that resonant stirring is effective for planets above ${\sim 0.5\, {\rm M_{Jup}}}$. By proving that these mechanisms can increase planet-stirring efficiency, we demonstrate that planets could still be stirring debris discs even in cases where conventional (secular) planet-stirring is insufficient.
ABSTRACT
When considering gaps in debris discs, a typical approach is to invoke clearing by an unseen planet within the gap, and derive the planet mass using Wisdom overlap or Hill radius arguments. ...However, this approach can be invalid if the disc is massive, because clearing would also cause planet migration. This could result in a calculated planet mass that is incompatible with the inferred disc mass, because the predicted planet would in reality be too small to carve the gap without significant migration. We investigate the gap that a single embedded planet would carve in a massive debris disc. We show that a degeneracy is introduced, whereby an observed gap could be carved by two different planets: either a high-mass, barely migrating planet, or a smaller planet that clears debris as it migrates. We find that, depending on disc mass, there is a minimum possible gap width that an embedded planet could carve (because smaller planets, rather than carving a smaller gap, would actually migrate through the disc and clear a wider region). We provide simple formulae for the planet-to-debris disc mass ratio at which planet migration becomes important, the gap width that an embedded planet would carve in a massive debris disc, and the interaction time-scale. We also apply our results to various systems, and in particular show that the disc of HD 107146 can be reasonably well-reproduced with a migrating, embedded planet. Finally, we discuss the importance of planet–debris disc interactions as a tool for constraining debris disc masses.
We investigate the general interaction between an eccentric planet and a coplanar debris disc of the same mass, using analytical theory and N-body simulations. Such an interaction could result from a ...planet–planet scattering or merging event. We show that when the planet mass is comparable to that of the disc, the former is often circularized with little change to its semimajor axis. The secular effect of such a planet can cause debris to apsidally anti-align with the planet's orbit (the opposite of what may be naïvely expected), leading to the counter-intuitive result that a low-mass planet may clear a larger region of debris than a higher mass body would. The interaction generally results in a double-ringed debris disc, which is comparable to those observed in HD 107146 and HD 92945. As an example we apply our results to HD 107146, and show that the disc's morphology and surface brightness profile can be well reproduced if the disc is interacting with an eccentric planet of comparable mass (∼10–100 Earth masses). This hypothetical planet had a pre-interaction semimajor axis of 30 or 40 au (similar to its present-day value) and an eccentricity of 0.4 or 0.5 (which would since have reduced to ∼0.1). Thus the planet (if it exists) presently resides near the inner edge of the disc, rather than between the two debris peaks as may otherwise be expected. Finally, we show that disc self-gravity can be important in this mass regime and, whilst it would not affect these results significantly, it should be considered when probing the interaction between a debris disc and a planet.
Abstract
We present the direct-imaging discovery of a giant planet orbiting the young star AF Lep, a 1.2
M
⊙
member of the 24 ± 3 Myr
β
Pic moving group. AF Lep was observed as part of our ongoing ...high-contrast imaging program targeting stars with astrometric accelerations between Hipparcos and Gaia that indicate the presence of substellar companions. Keck/NIRC2 observations in
L
′
with the vector vortex coronagraph reveal a point source, AF Lep b, at ≈340 mas, which exhibits orbital motion at the 6
σ
level over the course of 13 months. A joint orbit fit yields precise constraints on the planet’s dynamical mass of
3.2
−
0.6
+
0.7
M
Jup
, semimajor axis of
8.4
−
1.3
+
1.1
au, and eccentricity of
0.24
−
0.15
+
0.27
. AF Lep hosts a debris disk located at ∼50 au, but it is unlikely to be sculpted by AF Lep b, implying there may be additional planets in the system at wider separations. The stellar inclination (
i
*
=
54
−
9
+
11
°
) and orbital inclination (
i
o
=
50
−
12
+
9
°
) are in good agreement, which is consistent with the system having spin–orbit alignment. AF Lep b is the lowest-mass imaged planet with a dynamical mass measurement and highlights the promise of using astrometric accelerations as a tool to find and characterize long-period planets.
Remission rates in young people with Graves hyperthyroidism are less than 25% after 2 years of thionamide antithyroid drug (ATD).
We explored whether rituximab (RTX), a B-lymphocyte-depleting agent, ...would increase remission rates when administered with a short course of ATD.
This was an open-label, multicenter, single-arm, phase 2 trial in young people (ages, 12-20 years) with Graves hyperthyroidism. An A'Hern design was used to distinguish an encouraging remission rate (40%) from an unacceptable rate (20%). Participants presenting with Graves hyperthyroidism received 500 mg RTX and 12 months of ATD titrated according to thyroid function. ATDs were stopped after 12 months and primary outcome assessed at 24 months. Participants had relapsed at 24 months if thyrotropin was suppressed and free 3,5,3'-triiodothyronine was raised; they had received ATD between months 12 and 24; or they had thyroid surgery/radioiodine.
A total of 27 participants were recruited and completed the trial with no serious side effects linked to treatment. Daily carbimazole dose at 12 months was less than 5 mg in 21 of 27 participants. Thirteen of 27 participants were in remission at 24 months (48%, 90% one-sided CI, 35%-100%); this exceeded the critical value (9) for the A'Hern design and provided evidence of a promising remission rate. B-lymphocyte count at 28 weeks, expressed as a percentage of baseline, was related to likelihood of remission.
Adjuvant RTX, administered with a 12-month course of ATD, may increase the likelihood of remission in young people with Graves hyperthyroidism. A randomized trial of adjuvant RTX in young people with Graves hyperthyroidism is warranted.
ABSTRACT
Drastic changes in protoplanets’ orbits could occur in the early stages of planetary systems through interactions with other planets and their surrounding protoplanetary or debris discs. The ...resulting planetary system could exhibit orbits with moderate to high eccentricities and/or inclinations, causing planets to perturb one another as well as the disc significantly. The present work studies the evolution of systems composed of an initially inclined planet and a debris disc. We perform N-body simulations of a narrow, self-gravitating debris disc, and a single interior Neptune-like planet. We simulate systems with various initial planetary inclinations, from coplanar to polar configurations considering different separations between the planet and the disc. We find that except when the planet is initially on a polar orbit, the planet–disc system tends to reach a quasi-coplanar configuration with low vertical dispersion in the disc. When present, the Zeipel–Kozai–Lidov oscillations induced by the disc pump the planet’s eccentricity and, in turn, affect the disc structure. We also find that the resulting disc morphology in most of the simulations looks very similar in both radial and vertical directions once the simulations are converged. This contrasts strongly with massless disc simulations, where vertical disc dispersion is set by the initial disc-planet inclination and can be high for initially highly inclined planets. The results suggest caution in interpreting an unseen planet’s dynamical history based only on the disc’s appearance.
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