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Potentially habitable planets can orbit close enough to their host star that the differential gravity across their diameters can produce an elongated shape. Frictional forces inside the planet prevent the bulges from aligning perfectly with the host star and result in torques that alter the planet’s rotational angular momentum. Eventually the tidal torques fix the rotation rate at a specific frequency, a process called tidal locking. Tidally locked planets on circular orbits will rotate synchronously, but those on eccentric orbits will either librate or rotate super-synchronously. Although these features of tidal theory are well known, a systematic survey of the rotational evolution of potentially habitable exoplanets using classic equilibrium tide theories has not been undertaken. I calculate how habitable planets evolve under two commonly used models and find, for example, that one model predicts that the Earth’s rotation rate would have synchronized after 4.5 Gyr if its initial rotation period was 3 days, it had no satellites, and it always maintained the modern Earth’s tidal properties. Lower mass stellar hosts will induce stronger tidal effects on potentially habitable planets, and tidal locking is possible for most planets in the habitable zones of GKM dwarf stars. For fast-rotating planets, both models predict eccentricity growth and that circularization can only occur once the rotational frequency is similar to the orbital frequency. The orbits of potentially habitable planets of very late M dwarfs ( ) are very likely to be circularized within 1 Gyr, and hence, those planets will be synchronous rotators. Proxima b is almost assuredly tidally locked, but its orbit may not have circularized yet, so the planet could be rotating super-synchronously today. The evolution of the isolated and potentially habitable Kepler planet candidates is computed and about half could be tidally locked. Finally, projected TESS planets are simulated over a wide range of assumptions, and the vast majority of potentially habitable cases are found to tidally lock within 1 Gyr. These results suggest that the process of tidal locking is a major factor in the evolution of most of the potentially habitable exoplanets to be discovered in the near future.

We present three poems written from personal experience of living with primary progressive non-fluent aphasia (primary progressive apraxia of speech). The poems provide a window on this illness ‘from the inside’, and vividly illustrate how intellect and inner life may survive strikingly intact, even after speech is lost.

Artemisinin-based combination therapies (ACTs) are first-line treatments for uncomplicated Plasmodium falciparum malaria. ACT resistance is spreading in Asia but not yet in Africa. Reduced effects of ACT partner drugs have been reported but with little information regarding widely used artesunate/amodiaquine (ASAQ). We studied its efficacy in Zanzibar after 14 years as first-line treatment directly by an in vivo, single-armed trial and indirectly by prevalences of different genotypes in the P. falciparum chloroquine-resistance transporter, multidrug-resistance 1, and Kelch 13 propeller domain genes. In vivo efficacy was higher during 2017 (100%; 95% CI 97.4%-100%) than during 2002-2005 (94.7%; 95% CI 91.9%-96.7%) (p = 0.003). Molecular findings showed no artemisinin resistance-associated genotypes and major increases in genotypes associated with high sensitivity/efficacy for amodiaquine than before ASAQ was introduced. Thus, the efficacy of ASAQ is maintained and appears to be increased after long-term use in contrast to what is observed for other ACTs used in Africa.

Background Artemisinin-based combination therapy (ACT) resistant Plasmodium falciparum represents an increasing threat to Africa. Extended ACT regimens from standard 3 to 6 days may represent a means to prevent its development and potential spread in Africa. Methods Standard 3-day treatment with artemether–lumefantrine (control) was compared to extended 6-day treatment and single low-dose primaquine (intervention); in a randomized controlled, parallel group, superiority clinical trial of patients aged 1–65 years with microscopy confirmed uncomplicated P. falciparum malaria, enrolled in Bagamoyo district, Tanzania. The study evaluated parasite clearance, including proportion of PCR detectable P. falciparum on days 5 and 7 (primary endpoint), cure rate, post-treatment prophylaxis, safety and tolerability. Clinical, and laboratory assessments, including ECG were conducted during 42 days of follow-up. Blood samples were collected for parasite detection (by microscopy and PCR), molecular genotyping and pharmacokinetic analyses. Kaplan–Meier survival analyses were done for both parasite clearance and recurrence. Results A total of 280 patients were enrolled, 141 and 139 in the control and intervention arm, respectively, of whom 121 completed 42 days follow-up in each arm. There was no difference in proportion of PCR positivity across the arms at day 5 (80/130 (61.5%) vs 89/134 (66.4%), p = 0.44), or day 7 (71/129 (55.0%) vs 70/134 (52.2%), p = 0.71). Day 42 microscopy determined cure rates (PCR adjusted) were 97.4% (100/103) and 98.3% (110/112), p = 0.65, in the control and intervention arm, respectively. Microscopy determined crude recurrent parasitaemia during follow-up was 21/121 (17.4%) in the control and 14/121 (11.6%) in the intervention arm, p = 0.20, and it took 34 days and 42 days in the respective arms for 90% of the patients to remain without recurrent parasitaemia. Lumefantrine exposure was significantly higher in intervention arm from D3 to D42, but cardiac, biochemical and haematological safety was high and similar in both arms. Conclusion Extended 6-day artemether–lumefantrine treatment and a single low-dose of primaquine was not superior to standard 3-day treatment for ACT sensitive P. falciparum infections but, importantly, equally efficacious and safe. Thus, extended artemether–lumefantrine treatment may be considered as a future treatment regimen for ACT resistant P. falciparum , to prolong the therapeutic lifespan of ACT in Africa. Trial registration ClinicalTrials.gov, NCT03241901. Registered July 27, 2017 https://clinicaltrials.gov/show/NCT03241901

The determination of an exoplanet as rocky is critical for the assessment of planetary habitability. Observationally, the number of small-radius, transiting planets with accompanying mass measurements is insufficient for a robust determination of the transitional mass or radius. Theoretically, models predict that rocky planets can grow large enough to become gas giants when they reach ~10 MEarth, but the transitional mass remains unknown. Here I show how transit data, interpreted in the context of tidal theory, can reveal the critical radius that separates rocky and gaseous exoplanets. Standard tidal models predict that rocky exoplanets’ orbits are tidally circularized much more rapidly than gaseous bodies’, suggesting the former will tend to be found on circular orbits at larger semi-major axes than the latter. Well-sampled transits can provide a minimum eccentricity of the orbit, allowing a measurement of this differential circularization. I show that this effect should be present in the data from the Kepler spacecraft, but is not apparent. Instead, it appears that there is no evidence of tidal circularization at any planetary radius, probably because the publicly-available data, particularly the impact parameters, are not accurate enough. I also review the bias in the transit duration towards values that are smaller than that of planets on circular orbits, stressing that the azimuthal velocity of the planet determines the transit duration. The ensemble of Kepler planet candidates may be able to determine the critical radius between rocky and gaseous exoplanets, tidal dissipation as a function of planetary radius, and discriminate between tidal models.

We describe a software package called VPLanet that simulates fundamental aspects of planetary system evolution over Gyr timescales, with a focus on investigating habitable worlds. In this initial release, eleven physics modules are included that model internal, atmospheric, rotational, orbital, stellar, and galactic processes. Many of these modules can be coupled to simultaneously simulate the evolution of terrestrial planets, gaseous planets, and stars. The code is validated by reproducing a selection of observations and past results. VPLanet is written in C and designed so that the user can choose the physics modules to apply to an individual object at runtime without recompiling, i.e., a single executable can simulate the diverse phenomena that are relevant to a wide range of planetary and stellar systems. This feature is enabled by matrices and vectors of function pointers that are dynamically allocated and populated based on user input. The speed and modularity of VPLanet enables large parameter sweeps and the versatility to add/remove physical phenomena to assess their importance. VPLanet is publicly available from a repository that contains extensive documentation, numerous examples, Python scripts for plotting and data management, and infrastructure for community input and future development.

The αvβ6 integrin plays a key role in the activation of transforming growth factor-β (TGFβ), a pro-fibrotic mediator that is pivotal to the development of idiopathic pulmonary fibrosis (IPF). We identified a selective small molecule αvβ6 RGD-mimetic, GSK3008348, and profiled it in a range of disease relevant pre-clinical systems. To understand the relationship between target engagement and inhibition of fibrosis, we measured pharmacodynamic and disease-related end points. Here, we report, GSK3008348 binds to αvβ6 with high affinity in human IPF lung and reduces downstream pro-fibrotic TGFβ signaling to normal levels. In human lung epithelial cells, GSK3008348 induces rapid internalization and lysosomal degradation of the αvβ6 integrin. In the murine bleomycin-induced lung fibrosis model, GSK3008348 engages αvβ6, induces prolonged inhibition of TGFβ signaling and reduces lung collagen deposition and serum C3M, a marker of IPF disease progression. These studies highlight the potential of inhaled GSK3008348 as an anti-fibrotic therapy. The αvβ6 integrin is key in activating the pro-fibrotic cytokine TGFβ in idiopathic pulmonary fibrosis. Here, the authors show an inhaled small molecule αvβ6 inhibitor GSK3008348 induces prolonged inhibition of TGFβ signaling pathways in human and murine models of lung fibrosis via αvβ6 degradation.

We describe a software package called VPLanet that simulates fundamental aspects of planetary system evolution over Gyr timescales, with a focus on investigating habitable worlds. In this initial release, eleven physics modules are included that model internal, atmospheric, rotational, orbital, stellar, and galactic processes. Many of these modules can be coupled to simultaneously simulate the evolution of terrestrial planets, gaseous planets, and stars. The code is validated by reproducing a selection of observations and past results. VPLanet is written in C and designed so that the user can choose the physics modules to apply to an individual object at runtime without recompiling, i.e., a single executable can simulate the diverse phenomena that are relevant to a wide range of planetary and stellar systems. This feature is enabled by matrices and vectors of function pointers that are dynamically allocated and populated based on user input. The speed and modularity of VPLanet enables large parameter sweeps and the versatility to add/remove physical phenomena to assess their importance. VPLanet is publicly available from a repository that contains extensive documentation, numerous examples, Python scripts for plotting and data management, and infrastructure for community input and future development.

In a multiplanet system, tides acting on the inner planet can significantly affect the orbital evolution of the entire system. While tides usually damp eccentricities, a novel mechanism identified by Correia et al. (Astrophys J Lett 744, article id. L23, 2012 ) tends to raise eccentricities as a result of the tides’ effect on the inner planet’s rotation. Our analytical description of this spin-driven tidal (SDT) effect shows that, while the inner planet’s eccentricity undergoes pumping, the process is more completely described by an exchange of strength between the two eigenmodes of the dynamical system. Our analysis allows derivation of criteria for two-planet coplanar systems where the SDT effect can reverse tidal damping, and may preclude the effect’s being significant for realistic systems. For the specific case quantified by Correia et al., the effect is strong because of the large adopted tidal time lag, which may not be appropriate for the assumed Saturn-like inner planet. On the other hand, the effective Q for any given planet in exotic circumstances is very uncertain, so the SDT effect could play a role in planetary evolution.

Stellar radiation has conservatively been used as the key constraint to planetary habitability. We review here the effects of tides, exerted by the host star on the planet, on the evolution of the planetary spin. Tides initially drive the rotation period and the orientation of the rotation axis into an equilibrium state but do not necessarily lead to synchronous rotation. As tides also circularize the orbit, eventually the rotation period does equal the orbital period and one hemisphere will be permanently irradiated by the star. Furthermore, the rotational axis will become perpendicular to the orbit, i.e. the planetary surface will not experience seasonal variations of the insolation. We illustrate here how tides alter the spins of planets in the traditional habitable zone. As an example, we show that, neglecting perturbations due to other companions, the Super-Earth Gl581d performs two rotations per orbit and that any primordial obliquity has been eroded.