Abrupt transitions in turbulent thermoacoustic systems

Abrupt transitions to the state of thermoacoustic instability (TAI) in gas turbine combustors are a significant challenge plaguing the development of next-generation low-emission aircraft and power generation engines. In this paper, we present the observation of abrupt transition in three disparate turbulent thermoacoustic systems: an annular combustor, a swirl-stabilized combustor, and a preheated bluff-body stabilized combustor. Using a low-order stochastic thermoacoustic model, we show that the reported abrupt transitions occur when an initially stable, supercritical limit cycle becomes unstable, leading to a secondary bifurcation to a large amplitude limit cycle solution. The states of combustion noise and intermittency observed in these turbulent combustors are well captured by the additive stochastic noise in the model. Through amplitude reduction, we analyze the underlying potential functions affecting the stability of the observed dynamical states. Finally, we make use of the Fokker-Planck equation, educing the effect of stochastic fluctuations on subcritical and secondary bifurcation. We conclude that a high enough intensity of stochastic fluctuations which transforms a subcritical bifurcation into an intermittency-facilitated continuous transition may have little effect on the abrupt nature of secondary bifurcation. Our findings imply the high likelihood of abrupt transitions in turbulent combustors possessing higher-order nonlinearities where turbulence intensities are disproportionate to the large amplitude limit cycle solution

Emergence of order from chaos through a continuous phase transition in a turbulent reactive flow system

As the Reynolds number is increased, a laminar fluid flow becomes turbulent, and the range of time and length scales associated with the flow increases. Yet, in a turbulent reactive flow system, as we increase the Reynolds number, we observe the emergence of a single dominant time scale in the acoustic pressure fluctuations, as indicated by its loss of multifractality. Such emergence of order from chaos is intriguing and has hardly been studied. We perform experiments in a turbulent reactive flow system consisting of flame, acoustic, and hydrodynamic subsystems interacting nonlinearly. We study the evolution of short-time correlated dynamics between the acoustic field and the flame in the spatiotemporal domain of the system. The order parameter, defined as the fraction of the correlated dynamics, increases gradually from zero to one. We find that the susceptibility of the order parameter, correlation length, and correlation time diverge at a critical point between chaos and order. Our results show that the observed emergence of order from chaos is a continuous phase transition. Moreover, we provide experimental evidence that the critical exponents characterizing this transition fall in the universality class of directed percolation. Our study demonstrates how a real-world complex, non-equilibrium turbulent reactive flow system exhibits universal behavior near a critical point

Small-scale intermittency of premixed turbulent flames

Premixed turbulent flames, encountered in power generation and propulsion engines, are an archetype of a randomly advected, self-propagating surface. While such a flame is known to exhibit large-scale intermittent flapping, the possible intermittency of its small-scale fluctuations has been largely disregarded. Here, we experimentally reveal the inner intermittency of a premixed turbulent V-flame, while clearly distinguishing this small-scale feature from large-scale outer intermittency. From temporal measurements of the fluctuations of the flame, we find a frequency spectra that has a power-law subrange with an exponent close to $-2$, which is shown to follow from Kolmogorov phenomenology. Crucially, however, the moments of the temporal increment of the flame position are found to scale anomalously, with exponents that saturate at higher-orders. The implied extremely rapid, small-scale fluctuation events, hitherto overlooked, are relevant for modeling the heat release rate and other key properties of premixed turbulent flames

Eftilagimod alpha, a soluble lymphocyte activation gene-3 (LAG-3) protein plus pembrolizumab in patients with metastatic melanoma

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. BACKGROUND: To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of eftilagimod alpha (efti), a soluble lymphocyte activation gene-3 protein, in combination with the programmed cell death-1 (PD-1) antagonist pembrolizumab. METHODS: The study was divided into two parts; parts A and B, where part A was the dose escalation part and part B was an extension part of the study. Patients with metastatic melanoma were treated with efti plus the standard dose of pembrolizumab. Blood samples were assayed to determine plasma pharmacokinetic parameters, detect efti antibody formation and determine long-lived CD8 T cell responses and associated pharmacodynamic parameters. RESULTS: Twenty-four patients with melanoma received pembrolizumab and bi-weekly subcutaneous (s.c.) injections of efti at doses 1 mg, 6 mg or 30 mg/injection for up to 6 months (part A) or 30 mg/injection for up 12 months (part B). No dose-limiting toxicities were reported and the main adverse event for efti was injection site reactions. Sustained systemic exposure to the product was obtained in all patients following s.c. injections of 30 mg dose. Treatment induced an increase in activated CD8 and CD4 T cell counts, and in some of the soluble biomarkers, particularly interferon (IFN)-γ, a Th1 signature cytokine. An overall response rate (ORR) of 33% was observed in patients partly with pembrolizumab-refractory of part A and ORR of 50% was observed in patients with PD-1 naïve of part B. CONCLUSIONS: Efti was well tolerated in combination with pembrolizumab with encouraging antitumor activity. This warrants further clinical studies of this new combination therapy combining an antigen-presenting cell activator with an immune checkpoint inhibitor

Online information and support needs of women with advanced breast cancer: A qualitative analysis

Purpose: Women with advanced breast cancer (ABC) face significant adjustment challenges, yet few resources provide them with information and support, and attendance barriers can preclude access to face to face psychosocial support. This paper reports on two qualitative studies examining (i) whether information and support-seeking preferences of women with ABC could be addressed in an online intervention, and (ii) how an existing intervention for patients with early stage cancer could be adapted for women with ABC. Methods: Women with ABC participated in telephone interviews about their information and support- seeking preferences (N = 21) and evaluated an online intervention focused on early-stage cancer (N = 15). Interviews were transcribed and underwent thematic analysis using the framework method to identify salient themes. Results: Participants most commonly sought medical, lifestyle-related, and practical information/support; however, when presented with an online intervention, participants most commonly gave positive feedback on content on coping with emotional distress. Difficulty finding information and barriers to using common sources of information/support including health professionals, family and friends, and peers were reported; however, some women also reported not wanting information or support. All participants evaluating the existing intervention gave positive feedback on various components, with results suggesting an online intervention could be an effective means of providing information/support to women with ABC, given improved specificity/relevance to ABC and increased tailoring to individuals circumstances and preferences. Conclusions: Adaptation of an existing online intervention for early stage cancer appears a promising avenue to address the information and support needs of women with ABC

Eftilagimod alpha, a soluble lymphocyte activation gene-3 (LAG-3) protein plus pembrolizumab in patients with metastatic melanoma

Background To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of eftilagimod alpha (efti), a soluble lymphocyte activation gene-3 protein, in combination with the programmed cell death-1 (PD-1) antagonist pembrolizumab.Methods The study was divided into two parts; parts A and B, where part A was the dose escalation part and part B was an extension part of the study. Patients with metastatic melanoma were treated with efti plus the standard dose of pembrolizumab. Blood samples were assayed to determine plasma pharmacokinetic parameters, detect efti antibody formation and determine long-lived CD8 T cell responses and associated pharmacodynamic parameters.Results Twenty-four patients with melanoma received pembrolizumab and bi-weekly subcutaneous (s.c.) injections of efti at doses 1 mg, 6 mg or 30 mg/injection for up to 6 months (part A) or 30 mg/injection for up 12 months (part B). No dose-limiting toxicities were reported and the main adverse event for efti was injection site reactions. Sustained systemic exposure to the product was obtained in all patients following s.c. injections of 30 mg dose. Treatment induced an increase in activated CD8 and CD4 T cell counts, and in some of the soluble biomarkers, particularly interferon (IFN)-γ, a Th1 signature cytokine. An overall response rate (ORR) of 33% was observed in patients partly with pembrolizumab-refractory of part A and ORR of 50% was observed in patients with PD-1 naïve of part B.Conclusions Efti was well tolerated in combination with pembrolizumab with encouraging antitumor activity. This warrants further clinical studies of this new combination therapy combining an antigen-presenting cell activator with an immune checkpoint inhibitor