Mechanical oscillations in lasing microspheres

We investigate the feasibility of activating coherent mechanical oscillations in lasing microspheres by modulating the laser emission at a mechanical eigenfrequency. To this aim, 1.5% Nd3+:Barium-Titanium-Silicate microspheres with diameters around 50 {\mu}m were used as high quality factor (Q>10^6) whispering gallery mode lasing cavities. We have implemented a pump-and-probe technique in which the pump laser used to excite the Nd3+ ions is focused on a single microsphere with a microscope objective and a probe laser excites a specific optical mode with the evanescent field of a tapered fibre. The studied microspheres show monomode and multi-mode lasing action, which can be modulated in the best case up to 10 MHz. We have optically transduced thermally-activated mechanical eigenmodes appearing in the 50-70 MHz range, the frequency of which decreases with increasing the size of the microspheres. In a pump-and-probe configuration we observed modulation of the probe signal up to the maximum pump modulation frequency of our experimental setup, i.e., 20 MHz. This modulation decreases with frequency and is unrelated to lasing emission, pump scattering or thermal effects. We associate this effect to free-carrier-dispersion induced by multiphoton pump light absorption. On the other hand, we conclude that, in our current experimental conditions, it was not possible to resonantly excite the mechanical modes. Finally, we discuss on how to overcome these limitations by increasing the modulation frequency of the lasing emission and decreasing the frequency of the mechanical eigenmodes displaying a strong degree of optomechanical coupling.Comment: 17 pages, 5 figure

Mechanical oscillations in lasing microspheres

We investigate the feasibility of activating coherent mechanical oscillations in lasing microspheres by modulating the laser emission at a mechanical eigenfrequency. To this aim, 1.5%Nd3+:Barium-Titanium-Silicate microspheres with diameters around 50 μm were used as high quality factor (Q>106) whispering gallery mode lasing cavities. We have implemented a pump-and-probe technique in which the pump laser used to excite the Nd3+ ions is focused on a single microsphere with a microscope objective and a probe laser excites a specific optical mode with the evanescent field of a tapered fibre. The studied microspheres show monomode and multi-mode lasing action, which can be modulated in the best case up to 10 MHz. We have optically transduced thermally-activated mechanical eigenmodes appearing in the 50-70 MHz range, the frequency of which decreases with increasing the size of the microspheres. In a pump-and-probe configuration we observed modulation of the probe signal up to the maximum pump modulation frequency of our experimental setup, i.e., 20 MHz. This modulation decreases with frequency and is unrelated to lasing emission, pump scattering or thermal effects. We associate this effect to free-carrier-dispersion induced by multiphoton pump light absorption. On the other hand, we conclude that, in our current experimental conditions, it was not possible to resonantly excite the mechanical modes. Finally, we discuss on how to overcome these limitations by increasing the modulation frequency of the lasing emission and decreasing the frequency of the mechanical eigenmodes displaying a strong degree of optomechanical coupling

What is the duration of untreated psychosis worldwide? - A meta-analysis of pooled mean and median time and regional trends and other correlates across 369 studies.

Duration of untreated psychosis (DUP) has been associated with poor mental health outcomes. We aimed to meta-analytically estimate the mean and median DUP worldwide, evaluating also the influence of several moderating factors. This PRISMA/MOOSE-compliant meta-analysis searched for non-overlapping individual studies from inception until 9/12/2022, reporting mean ± s.d. or median DUP in patients with first episode psychosis (FEP), without language restrictions. We conducted random-effect meta-analyses, stratified analyses, heterogeneity analyses, meta-regression analyses, and quality assessment (PROSPERO:CRD42020163640). From 12 461 citations, 369 studies were included. The mean DUP was 42.6 weeks (95% confidence interval (CI) 40.6-44.6, k = 283, n = 41 320), varying significantly across continents (p < 0.001). DUP was (in descending order) 70.0 weeks (95% CI 51.6-88.4, k = 11, n = 1508) in Africa; 48.8 weeks (95% CI 43.8-53.9, k = 73, n = 12 223) in Asia; 48.7 weeks (95% CI 43.0-54.4, k = 36, n = 5838) in North America; 38.6 weeks (95% CI 36.0-41.3, k = 145, n = 19 389) in Europe; 34.9 weeks (95% CI 23.0-46.9, k = 11, n = 1159) in South America and 28.0 weeks (95% CI 20.9-35.0, k = 6, n = 1203) in Australasia. There were differences depending on the income of countries: DUP was 48.4 weeks (95% CI 43.0-48.4, k = 58, n = 5635) in middle-low income countries and 41.2 weeks (95% CI 39.0-43.4, k = 222, n = 35 685) in high income countries. Longer DUP was significantly associated with older age (β = 0.836, p < 0.001), older publication year (β = 0.404, p = 0.038) and higher proportion of non-White FEP patients (β = 0.232, p < 0.001). Median DUP was 14 weeks (Interquartile range = 8.8-28.0, k = 206, n = 37 215). In conclusion, DUP is high throughout the world, with marked variation. Efforts to identify and intervene sooner in patients with FEP, and to promote global mental health and access to early intervention services (EIS) are critical, especially in developing countries

Brain Performance versus Phase Transitions

We here illustrate how a well-founded study of the brain may originate in assuming analogies with phase-transition phenomena. Analyzing to what extent a weak signal endures in noisy environments, we identify the underlying mechanisms, and it results a description of how the excitability associated to (non-equilibrium) phase changes and criticality optimizes the processing of the signal. Our setting is a network of integrate-and-fire nodes in which connections are heterogeneous with rapid time-varying intensities mimicking fatigue and potentiation. Emergence then becomes quite robust against wiring topology modification—in fact, we considered from a fully connected network to the Homo sapiens connectome—showing the essential role of synaptic flickering on computations. We also suggest how to experimentally disclose significant changes during actual brain operation.The authors acknowledge support from the Spanish Ministry of Economy and Competitiveness under the project FIS2013-43201-P

LungBEAM: A prospective multicenter study to monitor stage IV NSCLC patients with EGFR mutations using BEAMing technology

Objectives: The aim of LungBEAM was to determine the value of a novel epidermal growth factor receptor (EGFR) mutation test in blood based on BEAMing technology to predict disease progression in advanced non-small cell lung cancer (NSCLC) patients treated with first- or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Another goal was to monitor the dynamics of EGFR mutations, as well as to track EGFR exon 20 p.T790M (p.T790M) resistance during treatment, as critical indicators of therapeutic efficacy and patient survival. Methods: Stage IV NSCLC patients with locally confirmed EGFR-TKI sensitizing mutations (ex19del and/or L858R) in biopsy tissue who were candidates to receive first- or second-generation EGFR-TKI as first-line therapy were included. Plasma samples were obtained at baseline and every 4 weeks during treatment until a progression-free survival (PFS) event or until study completion (72-week follow-up). The mutant allele fraction (MAF) was determined for each identified mutation using BEAMing. Results: A total of 68 of the 110 (61.8%) patients experienced a PFS event. Twenty-six patients (23.6%) presented with an emergent p.T790M mutation in plasma at some point during follow-up, preceding radiologic progression with a median of 76 (interquartile ratio: 54–111) days. Disease progression correlated with the appearance of p.T790M in plasma with a hazard ratio (HR) of 1.94 (95% confidence interval [CI], 1.48–2.54; p < 0.001). The HR for progression in patients showing increasing plasma sensitizing mutation levels (positive MAF slope) versus patients showing either decreasing or unchanged plasma mutation levels (negative or null MAF slopes) was 3.85 (95% CI, 2.01–7.36; p < 0.001). Conclusion: Detection and quantification of EGFR mutations in circulating tumor DNA using the highly sensitive BEAMing method should greatly assist in optimizing treatment decisions for advanced NSCLC patients. © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd

Redox activities and ROS, NO and phenylpropanoids production by axenically cultured intact olive seedling roots after interaction with a mycorrhizal or a pathogenic fungus

Las raíces de las plántulas de olivo, en cultivo axénico, fueron colocadas alternativamente en contacto con Rhizophagus irregulares (micorrícicos) o con hongos Verticillim dahliae (patógenos). También se incluyeron tratamientos MeJA. Las raíces intactas (generación de anión superóxido, superóxido dismutasa y actividades de peroxidasa) se midieron en las actividades in vivo del apoplasto. Todos nuestros resultados mostraron que las actividades redox apoplásticas de raíces de las plántulas intactas en contacto con el hongo micorriza compatible fueron claramente atenuados en comparación con el hongo patógeno o tratado con MeJA, incluso en las primeras etapas usadas en el tratamiento. Los fenoles totales, flavonoides y glucósidos fenilpropanoides, también fueron cuantificados. Las raíces en contacto con el hongo micorriza no mejoraron la biosíntesis de compuestos fenólicos con respecto a los controles, mientras que los de contacto con el patógeno mejoraron de forma significativa la biosíntesis de todas las fracciones fenólicas medidas. Las especies reactivas del oxígeno y la acumulación de óxido nítrico en las raíces fueron examinadas por microscopía de fluorescencia. Todos ellas presentaron una acumulación mucho mayor en las raíces en contacto con el patógeno que con el hongo micorriza. En total, estos resultados indican que las raíces de las plántulas intactas de olivo, claramente diferenciadas entre micorrizas y hongos patógenos, atenuan las reacciones de defensa contra la primera para facilitar su creación, mientras que induce una reacción de defensa fuerte y sostenida contra el segundo. Ambas especies reactivas de oxígeno y nitrógeno parecían estar involucrados en estas respuestas desde los primeros momentos de contacto. Sin embargo, se necesitan más investigaciones para aclarar la diafonía propuesta entre ellos y sus respectivas funciones en estas respuestas ya que las imágenes de fluorescencia de las raíces revelaron que las especies reactivas del oxígeno se acumulan principalmente en el apoplasto (congruente con las actividades redox medidas en este compartimento), mientras el óxido nítrico se almacena principalmente en el citosol.Roots of intact olive seedlings, axenically cultured, were alternatively placed in contact with Rhizophagus irregularis (mycorrhizal) or Verticillim dahliae (pathogenic) fungi. MeJA treatments were also included. In vivo redox activities in the apoplast of the intact roots (anion superoxide generation, superoxide dismutase and peroxidase activities) were measured. All our results showed that apoplastic redox activities of intact seedling roots in contact with the compatible mycorrhizal fungus were clearly attenuated in comparison with the pathogenic fungus or treated with MeJA, even at the early stages of treatment used. Total phenolics, flavonoids and phenylpropanoid glycosides were also quantified. Roots in contact with the mycorrhizal fungus did not enhance the biosynthesis of phenolic compounds with respect to controls, while those in contact with the pathogenic one significantly enhanced the biosynthesis of all phenolic fractions measured. Reactive oxygen species and nitric oxid accumulation in roots were examined by fluorescence microscopy. All of them presented much higher accumulation in roots in contact with the pathogenic than with the mycorrhizal fungus. Altogether these results indicate that intact olive seedling roots clearly differentiated between mycorrhizal and pathogenic fungi, attenuating defense reactions against the first to facilitate its establishment, while inducing a strong and sustained defense reaction against the second. Both reactive oxygen and nitrogen species seemed to be involved in these responses from the first moments of contact. However, further investigations are required to clarify the proposed crosstalk between them and their respective roles in these responses since fluorescence images of roots revealed that reactive oxygen species were mainly accumulated in the apoplast (congruently with the measured redox activities in this compartment) while nitric oxid was mainly stored in the cytosol.-- Ministerio de Ciencia e Innovación. Proyecto CGL2009-12406 -- Junta de Extremadura. Proyecto PRI09A023peerReviewe

Measurement of the Crab Nebula spectrum over three decades in energy with the MAGIC telescopes

The MAGIC stereoscopic system collected 69 hours of Crab Nebula data between October 2009 and April 2011. Analysis of this data sample using the latest improvements in the MAGIC stereoscopic software provided an unprecedented precision of spectral and night-by-night light curve determination at gamma rays. We derived a differential spectrum with a single instrument from 50 GeV up to almost 30 TeV with 5 bins per energy decade. At low energies, MAGIC results, combined with Fermi-LAT data, show a flat and broad Inverse Compton peak. The overall fit to the data between 1 GeV and 30 TeV is not well described by a log-parabola function. We find that a modified log-parabola function with an exponent of 2.5 instead of 2 provides a good description of the data ($\chi^2=35/26$). Using systematic uncertainties of red the MAGIC and Fermi-LAT measurements we determine the position of the Inverse Compton peak to be at (53 $\pm$ 3stat + 31syst -13syst) GeV, which is the most precise estimation up to date and is dominated by the systematic effects. There is no hint of the integral flux variability on daily scales at energies above 300 GeV when systematic uncertainties are included in the flux measurement. We consider three state- of-the-art theoretical models to describe the overall spectral energy distribution of the Crab Nebula. The constant B-field model cannot satisfactorily reproduce the VHE spectral measurements presented in this work, having particular difficulty reproducing the broadness of the observed IC peak. Most probably this implies that the assumption of the homogeneity of the magnetic field inside the nebula is incorrect. On the other hand, the time-dependent 1D spectral model provides a good fit of the new VHE results when considering a 80 {\mu}G magnetic field. However, it fails to match the data when including the morphology of the nebula at lower wavelengths.Comment: accepted by JHEAp, 9 pages, 6 figure

Detection of bridge emission above 50 GeV from the Crab pulsar with the MAGIC telescopes

The Crab pulsar is the only astronomical pulsed source detected at very high energy (VHE, E>100GeV) gamma-rays. The emission mechanism of VHE pulsation is not yet fully understood, although several theoretical models have been proposed. In order to test the new models, we measured the light curve and the spectra of the Crab pulsar with high precision by means of deep observations. We analyzed 135 hours of selected MAGIC data taken between 2009 and 2013 in stereoscopic mode. In order to discuss the spectral shape in connection with lower energies, 4.6 years of {\it Fermi}-LAT data were also analyzed. The known two pulses per period were detected with a significance of $8.0 \sigma$ and $12.6 \sigma$. In addition, significant emission was found between the two pulses with $6.2 \sigma$. We discovered the bridge emission above 50 GeV between the two main pulses. This emission can not be explained with the existing theories. These data can be used for testing new theoretical models.Comment: 5 pages, 4 figure

First broadband characterization and redshift determination of the VHE blazar MAGIC J2001+439

We aim to characterize the broadband emission from 2FGL J2001.1+4352, which has been associated with the unknown-redshift blazar MG4 J200112+4352. Based on its gamma-ray spectral properties, it was identified as a potential very high energy (VHE; E > 100 GeV) gamma-ray emitter. The source was observed with MAGIC first in 2009 and later in 2010 within a multi-instrument observation campaign. The MAGIC observations yielded 14.8 hours of good quality stereoscopic data. The object was monitored at radio, optical and gamma-ray energies during the years 2010 and 2011. The source, named MAGIC J2001+439, is detected for the first time at VHE with MAGIC at a statistical significance of 6.3 {\sigma} (E > 70 GeV) during a 1.3-hour long observation on 2010 July 16. The multi-instrument observations show variability in all energy bands with the highest amplitude of variability in the X-ray and VHE bands. We also organized deep imaging optical observations with the Nordic Optical Telescope in 2013 to determine the source redshift. We determine for the first time the redshift of this BL Lac object through the measurement of its host galaxy during low blazar activity. Using the observational evidence that the luminosities of BL Lac host galaxies are confined to a relatively narrow range, we obtain z = 0.18 +/- 0.04. Additionally, we use the Fermi-LAT and MAGIC gamma-ray spectra to provide an independent redshift estimation, z = 0.17 +/- 0.10. Using the former (more accurate) redshift value, we adequately describe the broadband emission with a one-zone SSC model for different activity states and interpret the few-day timescale variability as produced by changes in the high-energy component of the electron energy distribution.Comment: 17 pages, 15 figures, Accepted for publication in A&