Radial velocity surveys find Jupiter-mass planets with semimajor axes a less than 0.1 AU around $1% of solar-type stars; counting planets with a as large as 5 AU, the fraction of stars having planets reaches $10% (as found by Marcy et al. and Butler et al.). An examination of the distribution of semimajor axes shows that there is a clear excess of planets with orbital periods around 3 or 4 days, corresponding to a % 0:03 AU, with a sharp cutoff at shorter periods (see Fig. 1). It is believed that Jupiter-mass planets form at large distances from their parent stars; some fraction then migrates in to produce the short-period objects. We argue that a significant fraction of the hot Jupiters (a < 0:1 AU) may arise in binary star systems in which the orbit of the binary is highly inclined to the orbit of the planet. Mutual torques between the two orbits drive down the minimum separation or periapsis r p between the planet and its host star (the Kozai mechanism). This periapsis collapse is halted when tidal friction on the planet circularizes the orbit faster than Kozai torque can excite it. The same friction then circularizes the planet orbit, producing hot Jupiters with the peak of the semimajor axis distribution lying around 3 days. For the observed distributions of binary separation, eccentricity, and mass ratio, roughly 2.5% of planets with initial semimajor axis a p % 5 AU will migrate to within 0.1 AU of their parent star. Kozai migration could account for 10% or more of the observed hot Jupiters.

Acute asthma remains an important medical emergency, the most frequent cause of acute admissions in children and a major source of morbidity for adults with asthma. In all ages with asthma the presence of exacerbations is an important defining characteristic of asthma severity. In this review we will assess the epidemiology of acute asthma, the triggers of acute exacerbations and the mechanisms that underlie these exacerbations. We will also assess current treatments that prevent exacerbations, with an emphasis on the role of type 2 airway inflammation in the context of acute exacerbations and the novel treatments that effectively target this. Finally we will review current management strategies of the exacerbations themselves.

Background: Whether blood eosinophil counts and exhaled nitric oxide (FeNO) are associated with important outcomes in mild asthma is unclear. Methods: This question was explored in a pre-specified analysis of a 52week, open-label, randomized, parallel-group trial in patients with mild asthma receiving only reliever inhalers, comparing salbutamol 200µg asneeded, maintenance budesonide 200µg twice-daily with salbutamol as needed, and budesonide/formoterol 200/6µg as-needed. Outcomes were compared between patients with blood eosinophils of <0.15, 0.15-<0.3 and ≥0.3x109/L; FeNO of <20, 20-50 and >50ppb; and a composite score based on both. Results: The proportion of patients randomised to as-needed salbutamol having a severe exacerbation increased progressively with increasing blood eosinophil sub-group (4.1%, 6.5% and 19.5%; p=0.014). There were no significant interactions between either biomarker and the effect of as-needed budesonide/formoterol compared with as-needed salbutamol for either exacerbations or severe exacerbations. However, there were significant interactions between blood eosinophil sub-groups and the effect of maintenance budesonide compared with as needed salbutamol for exacerbations (p<0.001) and severe exacerbations (p<0.001). Maintenance budesonide was more effective than as-needed salbutamol in patients with eosinophils ≥0.3x109/L for exacerbations (odds ratio 0.13; 95% CI 0.05-0.33) and severe exacerbations (0.11; 0.03-0.45). This was not the case for eosinophils <0.15x109/L (odds ratio for exacerbations 1.15; 0.51-1.28 and severe exacerbations 5.72; 0.97-33.6). There was no consistent interaction between treatment response and FeNO or the composite score. Conclusions: In patients with mild asthma the effects of as-needed budesonide/formoterol on exacerbations are independent of biomarker profile, whereas the benefits of maintenance inhaled budesonide are greater in patients with high blood eosinophil counts.