Program Model Checking: A Practitioner's Guide

Program model checking is a verification technology that uses state-space exploration to evaluate large numbers of potential program executions. Program model checking provides improved coverage over testing by systematically evaluating all possible test inputs and all possible interleavings of threads in a multithreaded system. Model-checking algorithms use several classes of optimizations to reduce the time and memory requirements for analysis, as well as heuristics for meaningful analysis of partial areas of the state space Our goal in this guidebook is to assemble, distill, and demonstrate emerging best practices for applying program model checking. We offer it as a starting point and introduction for those who want to apply model checking to software verification and validation. The guidebook will not discuss any specific tool in great detail, but we provide references for specific tools

GJ 273: On the formation, dynamical evolution, and habitability of a planetary system hosted by an M dwarf at 3.75 parsec

Context. Planets orbiting low-mass stars such as M dwarfs are now considered a cornerstone in the search for life-harbouring planets. GJ 273 is a planetary system orbiting an M dwarf only 3.75 pc away, composed of two confirmed planets, GJ 273b and GJ 273c, and two promising candidates, GJ 273d and GJ 273e. Planet GJ 273b resides in the habitable zone. Currently, due to a lack of observed planetary transits, only the minimum masses of the planets are known: Mb sin ib=2.89 M⊕, Mc sin ic=1.18 M⊕, Md sin id=10.80 M⊕, and Me sin ie=9.30 M⊕. Despite being an interesting system, the GJ 273 planetary system is still poorly studied. Aims. We aim at precisely determine the physical parameters of the individual planets, in particular to break the mass–inclination degeneracy to accurately determine the mass of the planets. Moreover, we present thorough characterisation of planet GJ 273b in terms of its potential habitability. Methods. First, we explored the planetary formation and hydration phases of GJ 273 during the first 100 Myr. Secondly, we analysed the stability of the system by considering both the two- and four-planet configurations. We then performed a comparative analysis between GJ 273 and the Solar System, and searched for regions in GJ 273 which may harbour minor bodies in stable orbits, i.e. main asteroid belt and Kuiper belt analogues. Results. From our set of dynamical studies, we obtain that the four-planet configuration of the system allows us to break the mass– inclination degeneracy. From our modelling results, the masses of the planets are unveiled as: 2:89 ≤ Mb ≤ 3:03 M⊕, 1:18 ≤ Mc ≤ 1:24 M⊕, 10:80 ≤ Md ≤ 11:35 M⊕ and 9:30 ≤ Me ≤ 9:70 M⊕. These results point to a system likely composed of an Earth-mass planet, a super-Earth and two mini-Neptunes. From planetary formation models, we determine that GJ 273b was likely an efficient water captor while GJ 273c is probably a dry planet. We found that the system may have several stable regions where minor bodies might reside. Collectively, these results are used to comprehensively discuss the habitability of GJ 273bSpanish Ministry of Science and Education Ramón y Cajal programme ESP2017-87676-2-2 RYC-2012-09913CONICYT- FONDECYT/Chile Postdoctorado 3180405MIT’s Kavli Institut

Earth: Atmospheric Evolution of a Habitable Planet

Our present-day atmosphere is often used as an analog for potentially habitable exoplanets, but Earth's atmosphere has changed dramatically throughout its 4.5 billion year history. For example, molecular oxygen is abundant in the atmosphere today but was absent on the early Earth. Meanwhile, the physical and chemical evolution of Earth's atmosphere has also resulted in major swings in surface temperature, at times resulting in extreme glaciation or warm greenhouse climates. Despite this dynamic and occasionally dramatic history, the Earth has been persistently habitable--and, in fact, inhabited--for roughly 4 billion years. Understanding Earth's momentous changes and its enduring habitability is essential as a guide to the diversity of habitable planetary environments that may exist beyond our solar system and for ultimately recognizing spectroscopic fingerprints of life elsewhere in the Universe. Here, we review long-term trends in the composition of Earth's atmosphere as it relates to both planetary habitability and inhabitation. We focus on gases that may serve as habitability markers (CO2, N2) or biosignatures (CH4, O2), especially as related to the redox evolution of the atmosphere and the coupled evolution of Earth's climate system. We emphasize that in the search for Earth-like planets we must be mindful that the example provided by the modern atmosphere merely represents a single snapshot of Earth's long-term evolution. In exploring the many former states of our own planet, we emphasize Earth's atmospheric evolution during the Archean, Proterozoic, and Phanerozoic eons, but we conclude with a brief discussion of potential atmospheric trajectories into the distant future, many millions to billions of years from now. All of these 'Alternative Earth' scenarios provide insight to the potential diversity of Earth-like, habitable, and inhabited worlds.Comment: 34 pages, 4 figures, 4 tables. Review chapter to appear in Handbook of Exoplanet

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707