Deriving amplitude equations for weakly-nonlinear oscillators and their generalizations

AbstractResults by physicists on renormalization group techniques have recently sparked interest in the singular perturbations community of applied mathematicians. The survey paper, [Phys. Rev. E 54(1) (1996) 376–394], by Chen et al. demonstrated that many problems which applied mathematicians solve using disparate methods can be solved using a single approach. Analysis of that renormalization group method by Mudavanhu and O’Malley [Stud. Appl. Math. 107(1) (2001) 63–79; SIAM J. Appl. Math. 63(2) (2002) 373–397], among others, indicates that the technique can be streamlined. This paper carries that analysis several steps further to present an amplitude equation technique which is both well adapted for use with a computer algebra system and easy to relate to the classical methods of averaging and multiple scales

Antitumor activity and safety of the PARP inhibitor rucaparib in patients with high grade ovarian carcinoma and a germline or somatic BRCA1 or BRCA2 mutation: integrated analysis of data from Study 10 and ARIEL2

Objective: An integrated analysis was undertaken to characterize the antitumor activity and safety profile of the oral poly(ADP-ribose) polymerase inhibitor rucaparib in patients with relapsed high-grade ovarian carcinoma (HGOC). Methods: Eligible patients from Study 10 (NCT01482715) and ARIEL2 (NCT01891344) who received a starting dose of oral rucaparib 600 mg twice daily (BID) with or without food were included in these analyses. The integrated efficacy population included patients with HGOC and a deleterious germline or somatic BRCA1 or BRCA2 (BRCA1/2) mutation who received at least two prior chemotherapies and were sensitive, resistant, or refractory to platinum-based chemotherapy. The primary endpoint was investigator-assessed confirmed objective response rate (ORR). Secondary endpoints included duration of response (DOR) and progression-free survival (PFS). The integrated safety population included patients with HGOC who received at least one dose of rucaparib 600 mg BID, irrespective of BRCA1/2 mutation status and prior treatments. Results: In the efficacy population (n = 106), ORR was 53.8% (95% confidence interval [CI], 43.8–63.5); 8.5% and 45.3% of patients achieved complete and partial responses, respectively. Median DOR was 9.2 months (95% CI, 6.6–11.6). In the safety population (n = 377), the most frequent treatment-emergent adverse events (AEs) were nausea, asthenia/fatigue, vomiting, and anemia/hemoglobin decreased. The most common grade ≥ 3 treatment-emergent AE was anemia/hemoglobin decreased. Treatment-emergent AEs led to treatment interruption, dose reduction, and treatment discontinuation in 58.6%, 45.9%, and 9.8% of patients, respectively. No treatment-related deaths occurred. Conclusions: Rucaparib has antitumor activity in advanced BRCA1/2-mutated HGOC and a manageable safety profile

Governing terrorism through risk: Taking precautions, (un)knowing the future

The events of 9/11 appeared to make good on Ulrich Beck's claim that we are now living in a (global) risk society. Examining what it means to ‘govern through risk’, this article departs from Beck's thesis of risk society and its appropriation in security studies. Arguing that the risk society thesis problematically views risk within a macro-sociological narrative of modernity, this article shows, based on a Foucauldian account of governmentality, that governing terrorism through risk involves a permanent adjustment of traditional forms of risk management in light of the double infinity of catastrophic consequences and the incalculability of the risk of terrorism. Deploying the Foucauldian notion of ‘dispositif’, this article explores precautionary risk and risk analysis as conceptual tools that can shed light on the heterogeneous practices that are defined as the ‘war on terror’

Social preferences and network structure in a population of reef manta rays

Understanding how individual behavior shapes the structure and ecology ofpopulations is key to species conservation and management. Like manyelasmobranchs, manta rays are highly mobile and wide ranging species threatened byanthropogenic impacts. In shallow-water environments these pelagic rays often formgroups, and perform several apparently socially-mediated behaviors. Group structuresmay result from active choices of individual rays to interact, or passive processes.Social behavior is known to affect spatial ecology in other elasmobranchs, but this isthe first study providing quantitative evidence for structured social relationships inmanta rays. To construct social networks, we collected data from more than 500groups of reef manta rays over five years, in the Raja Ampat Regency of West Papua.We used generalized affiliation indices to isolate social preferences from non-socialassociations, the first study on elasmobranchs to use this method. Longer lastingsocial preferences were detected mostly between female rays. We detectedassortment of social relations by phenotype and variation in social strategies, with theoverall social network divided into two main communities. Overall network structurewas characteristic of a dynamic fission-fusion society, with differentiated relationshipslinked to strong fidelity to cleaning station sites. Our results suggest that fine-scaleconservation measures will be useful in protecting social groups of M. alfredi in theirnatural habitats, and that a more complete understanding of the social nature of mantarays will help predict population response

Size Doesn't Matter: Towards a More Inclusive Philosophy of Biology

notes: As the primary author, O’Malley drafted the paper, and gathered and analysed data (scientific papers and talks). Conceptual analysis was conducted by both authors.publication-status: Publishedtypes: ArticlePhilosophers of biology, along with everyone else, generally perceive life to fall into two broad categories, the microbes and macrobes, and then pay most of their attention to the latter. ‘Macrobe’ is the word we propose for larger life forms, and we use it as part of an argument for microbial equality. We suggest that taking more notice of microbes – the dominant life form on the planet, both now and throughout evolutionary history – will transform some of the philosophy of biology’s standard ideas on ontology, evolution, taxonomy and biodiversity. We set out a number of recent developments in microbiology – including biofilm formation, chemotaxis, quorum sensing and gene transfer – that highlight microbial capacities for cooperation and communication and break down conventional thinking that microbes are solely or primarily single-celled organisms. These insights also bring new perspectives to the levels of selection debate, as well as to discussions of the evolution and nature of multicellularity, and to neo-Darwinian understandings of evolutionary mechanisms. We show how these revisions lead to further complications for microbial classification and the philosophies of systematics and biodiversity. Incorporating microbial insights into the philosophy of biology will challenge many of its assumptions, but also give greater scope and depth to its investigations

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

Temperament Pathways to Childhood Disruptive Behavior and Adolescent Substance Abuse: Testing a Cascade Model

Abstract Temperament traits may increase risk for developmental psychopathology like Attention-Deficit/Hyperactivity Disorder (ADHD) and disruptive behaviors during childhood, as well as predisposing to substance abuse during adolescence. In the current study, a cascade model of trait pathways to adolescent substance abuse was examined. Component hypotheses were that (a) maladaptive traits would increase risk for inattention/hyperactivity, (b) inattention/hyperactivity would increase risk for disruptive behaviors, and (c) disruptive behaviors would lead to adolescent substance abuse. Participants were 674 children (486 boys) from 321 families in an ongoing, longitudinal high risk study that began when children were 3 years old. Temperament traits assessed were reactive control, resiliency, and negative emotionality, using examiner ratings on the California Q-Sort. Parent, teacher, and self ratings of inattention/hyperactivity, disruptive behaviors, and substance abuse were also obtained. Low levels of childhood reactive control, but not resiliency or negative emotionality, were associated with adolescent substance abuse, mediated by disruptive behaviors. Using a cascade model, family risk for substance abuse was partially mediated by reactive control, inattention/hyperactivity, and disruptive behavior. Some, but not all, temperament traits in childhood were related to adolescent substance abuse; these effects were mediated via inattentive/hyperactive and disruptive behaviors.This work was supported by NIAAA grant R01-AA12217 to Robert Zucker and Joel Nigg, NIAAA grant R37-AA07065 to Robert Zucker and Hiram Fitzgerald, and NIMH grant R01-MH59105 to Joel Nigg. Martel was supported by 1 F31 MH075533-01A2.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64507/1/#167, Martel 2009, Temperament path to disruptive behav and sub abuse JACP.pd