A prognostic score for non-small cell lung cancer resected after neoadjuvant therapy in comparison with the tumor-node-metastases classification and major pathological response.

Studies validating the prognostic accuracy of the tumor-node-metastases (TNM) classification in patients with lung cancer treated by neoadjuvant therapy are scarce. Tumor regression, particularly major pathological response (MPR), is an acknowledged prognostic factor in this setting. We aimed to validate a novel combined prognostic score. This retrospective single-center study was conducted on 117 consecutive patients with non-small cell lung cancer resected after neoadjuvant treatment at a Swiss University Cancer Center between 2000 and 2016. All cases were clinicopathologically re-evaluated. We assessed the prognostic performance of a novel prognostic score (PRSC) combining T-category, lymph node status, and MPR, in comparison with the eighth edition of the TNM classification (TNM8), the size adapted TNM8 as proposed by the International Association for the Study of Lung Cancer (IASLC) and MPR alone. The isolated ypT-category and the combined TNM8 stages accurately differentiated overall survival (OS, stage p = 0.004) and disease-free survival (DFS, stage p = 0.018). Tumor regression had a prognostic impact. Optimal cut-offs for MPR emerged as 65% for adenocarcinoma and 10% for non-adenocarcinoma and were statistically significant for survival (OS p = 0.006, DFS p < 0.001). The PRSC differentiated between three prognostic groups (OS and DFS p < 0.001), and was superior compared to the stratification using MPR alone or the TNM8 systems, visualized by lower Akaike (AIC) and Bayesian information criterion (BIC) values. In the multivariate analyses, stage III tumors (HR 4.956, p = 0.003), tumors without MPR (HR 2.432, p = 0.015), and PRSC high-risk tumors (HR 5.692, p < 0.001) had significantly increased risks of occurring death. In conclusion, we support 65% as the optimal cut-off for MPR in adenocarcinomas. TNM8 and MPR were comparable regarding their prognostic significance. The novel prognostic score performed distinctly better regarding OS and DFS

Integration of Spatial Distortion Effects in a 4D Computational Phantom for Simulation Studies in Extra-Cranial MRI-guided Radiation Therapy: Initial Results.

PurposeSpatial distortions in magnetic resonance imaging (MRI) are mainly caused by inhomogeneities of the static magnetic field, nonlinearities in the applied gradients, and tissue‐specific magnetic susceptibility variations. These factors may significantly alter the geometrical accuracy of the reconstructed MR image, thus questioning the reliability of MRI for guidance in image‐guided radiation therapy. In this work, we quantified MRI spatial distortions and created a quantitative model where different sources of distortions can be separated. The generated model was then integrated into a four‐dimensional (4D) computational phantom for simulation studies in MRI‐guided radiation therapy at extra‐cranial sites.MethodsA geometrical spatial distortion phantom was designed in four modules embedding laser‐cut PMMA grids, providing 3520 landmarks in a field of view of (345 × 260 × 480) mm3. The construction accuracy of the phantom was verified experimentally. Two fast MRI sequences for extra‐cranial imaging at 1.5 T were investigated, considering axial slices acquired with online distortion correction, in order to mimic practical use in MRI‐guided radiotherapy. Distortions were separated into their sources by acquisition of images with gradient polarity reversal and dedicated susceptibility calculations. Such a separation yielded a quantitative spatial distortion model to be used for MR imaging simulations. Finally, the obtained spatial distortion model was embedded into an anthropomorphic 4D computational phantom, providing registered virtual CT/MR images where spatial distortions in MRI acquisition can be simulated.ResultsThe manufacturing accuracy of the geometrical distortion phantom was quantified to be within 0.2 mm in the grid planes and 0.5 mm in depth, including thickness variations and bending effects of individual grids. Residual spatial distortions after MRI distortion correction were strongly influenced by the applied correction mode, with larger effects in the trans‐axial direction. In the axial plane, gradient nonlinearities caused the main distortions, with values up to 3 mm in a 1.5 T magnet, whereas static field and susceptibility effects were below 1 mm. The integration in the 4D anthropomorphic computational phantom highlighted that deformations can be severe in the region of the thoracic diaphragm, especially when using axial imaging with 2D distortion correction. Adaptation of the phantom based on patient‐specific measurements was also verified, aiming at increased realism in the simulation.ConclusionsThe implemented framework provides an integrated approach for MRI spatial distortion modeling, where different sources of distortion can be quantified in time‐dependent geometries. The computational phantom represents a valuable platform to study motion management strategies in extra‐cranial MRI‐guided radiotherapy, where the effects of spatial distortions can be modeled on synthetic images in a virtual environment

Far-infrared photo-conductivity of electrons in an array of nano-structured antidots

We present far-infrared (FIR) photo-conductivity measurements for a two-dimensional electron gas in an array of nano-structured antidots. We detect, resistively and spectrally resolved, both the magnetoplasmon and the edge-magnetoplasmon modes. Temperature-dependent measurements demonstrates that both modes contribute to the photo resistance by heating the electron gas via resonant absorption of the FIR radiation. Influences of spin effect and phonon bands on the collective excitations in the antidot lattice are observed.Comment: 5 pages, 3 figure

Edge and bulk effects in the Terahertz-photoconductivity of an antidot superlattice

We investigate the Terahertz(THz)-response of a square antidot superlattice by means of photoconductivity measurements using a Fourier-transform-spectrometer. We detect, spectrally resolved, the cyclotron resonance and the fundamental magnetoplasmon mode of the periodic superlattice. In the dissipative transport regime both resonances are observed in the photoresponse. In the adiabatic transport regime, at integer filling factor $\nu =2$, only the cyclotron resonance is observed. From this we infer that different mechanisms contribute to converting the absorption of THz-radiation into photoconductivity in the cyclotron and in the magnetoplasmon resonances, respectively.Comment: 15 pages, 4 figures, submitted to Phys. Rev.

Combined deletion of Glut1 and Glut3 impairs lung adenocarcinoma growth.

Glucose utilization increases in tumors, a metabolic process that is observed clinically by <sup>18</sup> F-fluorodeoxyglucose positron emission tomography ( <sup>18</sup> F-FDG-PET). However, is increased glucose uptake important for tumor cells, and which transporters are implicated in vivo? In a genetically-engineered mouse model of lung adenocarcinoma, we show that the deletion of only one highly expressed glucose transporter, Glut1 or Glut3, in cancer cells does not impair tumor growth, whereas their combined loss diminishes tumor development. <sup>18</sup> F-FDG-PET analyses of tumors demonstrate that Glut1 and Glut3 loss decreases glucose uptake, which is mainly dependent on Glut1. Using <sup>13</sup> C-glucose tracing with correlated nanoscale secondary ion mass spectrometry (NanoSIMS) and electron microscopy, we also report the presence of lamellar body-like organelles in tumor cells accumulating glucose-derived biomass, depending partially on Glut1. Our results demonstrate the requirement for two glucose transporters in lung adenocarcinoma, the dual blockade of which could reach therapeutic responses not achieved by individual targeting

A biominősítés hatása a fogyasztók érzékelésére és attitűdjére csokoládék esetén

The time–energy information of ultrashort X-ray free-electron laser pulses generated by the Linac Coherent Light Source is measured with attosecond resolution via angular streaking of neon 1s photoelectrons. The X-ray pulses promote electrons from the neon core level into an ionization continuum, where they are dressed with the electric field of a circularly polarized infrared laser. This induces characteristic modulations of the resulting photoelectron energy and angular distribution. From these modu- lations we recover the single-shot attosecond intensity structure and chirp of arbitrary X-ray pulses based on self-amplified spontaneous emission, which have eluded direct measurement so far. We characterize individual attosecond pulses, including their instantaneous frequency, and identify double pulses with well-defined delays and spectral properties, thus paving the way for X-ray pump/X-ray probe attosecond free-electron laser science

Lightwave-driven quasiparticle collisions on a subcycle timescale

Ever since Ernest Rutherford scattered alpha-particles from gold foils(1), collision experiments have revealed insights into atoms, nuclei and elementary particles(2). In solids, many-body correlations lead to characteristic resonances(3)-called quasiparticles-such as excitons, dropletons(4), polarons and Cooper pairs. The structure and dynamics of quasiparticles are important because they define macroscopic phenomena such as Mott insulating states, spontaneous spin-and charge-order, and high-temperature superconductivity(5). However, the extremely short lifetimes of these entities(6) make practical implementations of a suitable collider challenging. Here we exploit lightwave-driven charge transport(7-24), the foundation of attosecond science(9-13), to explore ultrafast quasiparticle collisions directly in the time domain: a femtosecond optical pulse creates excitonic electron-hole pairs in the layered dichalcogenide tungsten diselenide while a strong terahertz field accelerates and collides the electrons with the holes. The underlying dynamics of the wave packets, including collision, pair annihilation, quantum interference and dephasing, are detected as light emission in high-order spectral sidebands(17-19) of the optical excitation. A full quantum theory explains our observations microscopically. This approach enables collision experiments with various complex quasiparticles and suggests a promising new way of generating sub-femtosecond pulses