Risk of aortic aneurysm or dissection following use of fluoroquinolones: a retrospective multinational network cohort study

Background: Fluoroquinolones (FQs) are commonly used to treat urinary tract infections (UTIs), but some studies have suggested they may increase the risk of aortic aneurysm or dissection (AA/AD). However, no large-scale international study has thoroughly assessed this risk. // Methods: A retrospective cohort study was conducted using a large, distributed network analysis across 14 databases from 5 countries (United States, South Korea, Japan, Taiwan, and Australia). The study included 13,588,837 patients aged 35 or older who initiated systemic fluoroquinolones (FQs) or comparable antibiotics (trimethoprim with or without sulfamethoxazole [TMP] or cephalosporins [CPHs]) for UTI treatment in the outpatient setting between JAN 01, 2010 and DEC 31, 2019. Patients were included if at the index date they had at least 365 days of prior observation and were not hospitalised for any reason on or within 7 days prior to the index date. The primary outcome was AA/AD occurrence within 60 days of exposure, with secondary outcomes examining AA and AD separately. Cox proportional hazards models with 1:1 propensity score (PS) matching were used to estimate the risk, with results calibrated using negative control outcomes. Analyses were subjected to pre-defined study diagnostics, and only those passing all diagnostics were reported. Hazard ratios (HRs) were pooled using Bayesian random-effects meta-analysis. // Findings: Among analyses that passed diagnostics there were 1,954,798 and 1,195,962 propensity-matched pairs for the FQ versus TMP and FQ versus CPH comparisons respectively. For the 60-day follow-up there was no difference in risk of AA/AD between FQ and TMP (absolute rate difference [ARD], 0.21 per 1000 person-year; calibrated HR, 0.91 [95% CI 0.73–1.10]). There was no significant difference in risk for FQ versus CPH (ARD, 0.11 per 1000 person-year; calibrated HR, 1.01 [95% CI 0.82–1.25]). // Interpretation: This large-scale study used a rigorous design with objective diagnostics to address bias and confounding. There was no increased risk of AA/AD associated with FQ compared to TMP or CPH in patients treated for UTI in the outpatient setting. As we only examined FQ used to treat UTIs in the outpatient setting, the results may not be generalisable to other indications with different severity. // Funding: Yonsei University College of Medicine, Government-wide R&D Fund project for infectious disease research (GFID), Republic of Korea, National Health and Medical Research Council (NHMRC) Australian Government. Department of Veterans Affairs (VA) Informatics and Computing Infrastructure (VINCI), Department of Veterans Affairs, the United States Government

A self-stabilized coherent phonon source driven by optical forces

[EN] We report a novel injection scheme that allows for phonon lasing in a one-dimensional optomechanical photonic crystal, in a sideband unresolved regime and with cooperativity values as low as 10-2. It extracts energy from a cw infrared laser source and is based on the triggering of a thermooptical/free-carrier-dispersion self-pulsing limit-cycle, which anharmonically modulates the radiation pressure force. The large amplitude of the coherent mechanical motion acts as a feedback that stabilizes and entrains the self-pulsing oscillations to simple fractions of the mechanical frequency. A manifold of frequency-entrained regions with two different mechanical modes (at 54 and 122 MHz) are observed as a result of the wide tuneability of the natural frequency of the self-pulsing. The system operates at ambient conditions of pressure and temperature in a silicon platform, which enables its exploitation in sensing, intra-chip metrology or time-keeping applications.This work was supported by the European Comission project TAILPHOX (ICT-FP7-233883), the ERC Advanced Grant SOULMAN (ERC-FP7-321122) and the Spanish MINECO project TAPHOR (MAT2012-31392). The authors sincerely thank B. Djafari-Rouhani, Y. Pennec and M. Oudich for the design of the OM photonic crystal, A. Trifonova, S. Valenzuela and E. Weig for a critical reading of the manuscript and A. Tredicucci for fruitful discussions. A. M and A. G thank L. Bellieres and N. Sanchez-Losilla for their contributions in the OM photonic crystal etching processes. DNU and JGB gratefully acknowledge the support of a Beatriu de Pinos and a Juan de la Cierva postdoctoral fellowship, respectively.Navarro Urríos, D.; Capuj, NE.; Gomis-Bresco, J.; Alzina, F.; Pitanti, A.; Griol Barres, A.; Martínez Abietar, AJ.... (2015). A self-stabilized coherent phonon source driven by optical forces. Scientific Reports. 5(15733):1-7. https://doi.org/10.1038/srep15733S17515733Feng, X. L., White, C. J., Hajimiri, A. & Roukes, M. L. A self-sustaining ultrahigh-frequency nanoelectromechanical oscillator. Nat. Nanotech. 3, 342 (2008).Aspelmeyer, M., Kippenberg, T. J. & Marquardt, F. Cavity optomechanics. Rev. Mod. Phys. 86, 1391 (2014).Pikovsky, A., Rosenblum, M. & Kurths, J. Synchronization: a universal concept in nonlinear sciences (Cambridge university press, Cambridge 2003).Heinrich, G., Ludwig, M., Qian, J., Kubala, B. & Marquardt, F. Collective dynamics in optomechanical arrays. Phys. Rev. Lett. 107, 043603 (2011).Zhang, M. et al. Synchronization of micromechanical oscillators using light. Phys. Rev. Lett. 109, 233906 (2012).Bagheri, M., Poot, M., Fan, L., Marquardt, F. & Tang, H. X. Photonic cavity synchronization of nanomechanical oscillators. Phys. Rev. Lett. 111, 213902 (2013).Matheny, M. H. et al. Phase synchronization of two anharmonic nanomechanical oscillators. Phys. Rev. Lett. 112, 014101 (2014).Mahboob, I., Nishiguchi, K., Fujiwara, A. & Yamaguchi, H. Phonon Lasing in an Electromechanical Resonator. Phys. Rev. Lett. 110, 127202 (2013).Grudinin, I. S., Lee, H., Painter, O. & Vahala, K. J. Phonon laser action in a tunable two-level system. Phys. Rev. Lett. 104, 083901 (2010).Kippenberg, T. J., Rokhsari, H., Carmon, T., Scherer, A. & Vahala, K. J. Analysis of radiation-pressure induced mechanical oscillation of an optical microcavity. Phys. Rev. Lett. 95, 033901 (2005).Kippenberg, T. J. & Vahala, K. J. Cavity optomechanics: back-action at the mesoscale. Science 321, 1172–1176 (2008).Schliesser, A. & Kippenberg, T. J. in Cavity Optomechanics, Aspelmeyer M., Kippenberg T. J. & Marquardt F. Eds (Springer: Berlin Heidelberg, 2014), chap. 6.Roels, J. et al. Parametric instability of an integrated micromechanical oscillator by means of active optomechanical feedback. Opt. Express 19, 13081–13088 (2011).Villanueva, L. G. et al. A nanoscale parametric feedback oscillator. Nano Lett. 11, 5054–5059 (2011).Gomis-Bresco, J. et al. A one-dimensional optomechanical crystal with a complete phononic band gap. Nat. Commun. 5, 4452 (2014).Barclay, P. E., Srinivasan, K. & Painter, O. Nonlinear response of silicon photonic crystal microresonators excited via an integrated waveguide and fiber taper. Opt. Express 13, 801 (2005).Johnson, S. G. et al. Perturbation theory for Maxwell’s equations with shifting material boundaries. Phys. Rev. E 65, 066611 (2003).Chen, S., Zhang, L., Fei, Y. & Cao, T. Bistability and self-pulsation phenomena in silicon microring resonators based on nonlinear optical effects. Opt. Express 20, 7454 (2012).Armaroli, A. et al. Oscillatory dynamics in nanocavities with noninstantaneous Kerr response. Phys. Rev. A 84, 053816 (2011).Mancinelli, M., Borghi, M., Ramiro-Manzano, F., Fedeli, J. M. & Pavesi, L. Chaotic dynamics in coupled resonator sequences. Opt. Express 22, 14505 (2014).Xu, Q. & Lipson, M. Carrier-induced optical bistability in silicon ring resonators. Opt. Lett. 31, 341 (2006).Johnson, T. J., Borselli, M. & Painter, O. Self-induced optical modulation of the transmission through a high-Q silicon microdisk resonator. Opt. Express, 14, 817–831 (2006).Pernice, W. H., Li, M. & Tang, H. X. Time-domain measurement of optical transport in silicon micro-ring resonators. Opt. Express, 18, 18438–18452 (2010).Yang, J. et al. Radio frequency regenerative oscillations in monolithic high-Q/V heterostructured photonic crystal cavities. Appl. Phys. Lett. 104, 061104 (2014).Zhang, L., Fei, Y., Cao, Y., Lei, X. & Chen, S. Experimental observations of thermo-optical bistability and self-pulsation in silicon microring resonators. JOSA B 31, 201–206 (2014).Deng, Y., Liu, F., Leseman, Z. & Hossein-Zadeh, M. Thermo-optomechanical oscillator for sensing applications. Opt. Express 21, 4653–4664 (2013).Lifshitz, R. & Cross, M. C. Response of parametrically driven nonlinear coupled oscillators with application to micromechanical and nanomechanical resonator arrays. Phys. Rev. B 67, 134302 (2003)

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Harnessing fluctuations in thermodynamic computing via time-reversal symmetries

We experimentally demonstrate that highly structured distributions of work emerge during even the simple task of erasing a single bit. These are signatures of a refined suite of time-reversal symmetries in distinct functional classes of microscopic trajectories. As a consequence, we introduce a broad family of conditional fluctuation theorems that the component work distributions must satisfy. Since they identify entropy production, the component work distributions encode the frequency of various mechanisms of both success and failure during computing, as well giving improved estimates of the total irreversibly dissipated heat. This new diagnostic tool provides strong evidence that thermodynamic computing at the nanoscale can be constructively harnessed. We experimentally verify this functional decomposition and the new class of fluctuation theorems by measuring transitions between flux states in a superconducting circuit

Harnessing fluctuations in thermodynamic computing via time-reversal symmetries

We experimentally demonstrate that highly structured distributions of work emerge during even the simple task of erasing a single bit. These are signatures of a refined suite of time-reversal symmetries in distinct functional classes of microscopic trajectories. As a consequence, we introduce a broad family of conditional fluctuation theorems that the component work distributions must satisfy. Since they identify entropy production, the component work distributions encode the frequency of various mechanisms of both success and failure during computing, as well giving improved estimates of the total irreversibly dissipated heat. This new diagnostic tool provides strong evidence that thermodynamic computing at the nanoscale can be constructively harnessed. We experimentally verify this functional decomposition and the new class of fluctuation theorems by measuring transitions between flux states in a superconducting circuit

Nonequilibrium thermodynamics of erasure with superconducting flux logic

We implement a thermal-fluctuation-driven logical bit reset on a superconducting flux logic cell. We show that the logical state of the system can be continuously monitored with only a small perturbation to the thermally activated dynamics at 500 mK. We use the trajectory information to derive a single-shot estimate of the work performed on the system per logical cycle. We acquire a sample of 105 erasure trajectories per protocol and show that the work histograms agree with both microscopic theory and global fluctuation theorems. The results demonstrate how to design and diagnose complex, high-speed, and thermodynamically efficient computing using superconducting technology