The classification for invasive lung adenocarcinoma by the International Association for the Study of Lung Cancer, American Thoracic Society, European Respiratory Society, and WHO is based on the ...predominant histologic pattern-lepidic (LEP), papillary (PAP), acinar (ACN), micropapillary (MIP), or solid (SOL)-present in the tumor. This classification has not been tested in multi-institutional cohorts or clinical trials or tested for its predictive value regarding survival from adjuvant chemotherapy (ACT).
Of 1,766 patients in the IALT, JBR.10, CALGB 9633 (Alliance), and ANITA ACT trials included in the LACE-Bio study, 725 had adenocarcinoma. Histologies were reclassified according to the new classification and then collapsed into three groups (LEP, ACN/PAP, and MIP/SOL). Primary end point was overall survival (OS); secondary end points were disease-free survival (DFS) and specific DFS (SDFS). Hazard ratios (HRs) and 95% CIs were estimated through multivariable Cox models stratified by trial. Prognostic value was estimated in the observation arm and predictive value by a treatment effect interaction with histologic subgroups. Significance level was set at .01 for pooled analysis.
A total of 575 patients were included in this analysis. OS was not prognostically different between histologic subgroups, but univariable DFS and SDFS were worse for MIP/SOL compared with LEP or ACN/PAP subgroup (P < .01); this remained marginally significant after adjustment. MIP/SOL patients (but not ACN/PAP) derived DFS and SDFS but not OS benefit from ACT (OS: HR, 0.71; 95% CI, 0.51 to 0.99; interaction P = .18; DFS: HR, 0.60; 95% CI, 0.44 to 0.82; interaction P = < .01; and SDFS: HR, 0.59; 95% CI, 0.42 to 0.81; interaction P = .01).
The new lung adenocarcinoma classification based on predominant histologic pattern was not predictive for ACT benefit for OS, but it seems predictive for disease-specific outcomes.
Inertia is a measure of a power system's capability to counteract frequency disturbances: in conventional power networks, inertia is approximately constant over time, which contributes to network ...stability. However, as the share of renewable energy sources increases, the inertia associated to synchronous generators declines, which may pose a threat to the overall stability. Reliably estimating the inertia of power systems dominated by inverted-connected sources has therefore become of paramount importance. We develop a framework for the continuous estimation of the inertia in an electric power system, exploiting state-of-the-art artificial intelligence techniques. We perform an in-depth investigation based on power spectra analysis and input-output correlations to explain how the artificial neural network operates in this specific realm, thus shedding light on the input features necessary for proper neural-network training. We validate our approach on a heterogeneous power network comprising synchronous generators, static compensators and converter-interfaced generation: our results highlight how different devices are characterized by distinct spectral footprints - a feature that must be taken into account by transmission system operators when performing online network stability analyses.
We study the instability thresholds of the stationary emission of a quantum cascade laser with optical feedback described by the Lang Kobayashi model. We introduce an exact linear stability analysis ...and an approximated one for an unipolar lasers, who does not exhibit relaxation oscillations, and investigate the regimes of the emitter beyond the continuous wave instability threshold, depending on the number and density of the external cavity modes. We then show that a unipolar laser with feedback can exhibit coherent multimode oscillations that indicate spontaneous phase-locking.
The dynamics of a multimode quantum cascade laser, are studied in a model based on effective semiconductor Maxwell-Bloch equations, encompassing key features for the radiation-medium interaction such ...as an asymmetric frequency dependent gain and refractive index as well as the phase-amplitude coupling provided by the linewidth enhancement factor. By considering its role and that of the free spectral range, we find the conditions in which the traveling wave emitted by the laser at the threshold can be destabilized by adjacent modes, thus leading the laser emission towards chaotic or regular multimode dynamics. In the latter case our simulations show that the field oscillations are associated to self-confined structures which travel along the laser cavity, bridging mode-locking and solitary wave propagation. In addition, we show how a RF modulation of the bias current leads to active mode-locking yielding high-contrast, picosecond pulses. Our results compare well with recent experiments on broad-band THz-QCLs and may help in the understanding of the conditions for the generation of ultrashort pulses and comb operation in mid-IR and THz spectral regions.
•Many neuro-behavioral chronic diseases show sex differences in vulnerability.•Endocrine disruption during critical periods can affect susceptibility to disease.•BPA and phthalates alter emotional, ...motor, cognitive, socio-sexual and parental behavior.•BPA and phthalate effects are sex specific in rodent models and children.•Sex is a critical variable for the effects of endocrine disrupting chemicals.
Sex is a fundamental biological characteristic that influences many aspects of an organism’s phenotype, including neurobiological functions and behavior as a result of species-specific evolutionary pressures. Sex differences have strong implications for vulnerability to disease and susceptibility to environmental perturbations. Endocrine disrupting chemicals (EDCs) have the potential to interfere with sex hormones functioning and influence development in a sex specific manner. Here we present an updated descriptive review of findings from animal models and human studies regarding the current evidence for altered sex-differences in behavioral development in response to early exposure to EDCs, with a focus on bisphenol A and phthalates. Overall, we show that animal and human studies have a good degree of consistency and that there is strong evidence demonstrating that EDCs exposure during critical periods of development affect sex differences in emotional and cognitive behaviors. Results are more heterogeneous when social, sexual and parental behaviors are considered. In order to pinpoint sex differences in environmentally-driven disease vulnerabilities, researchers need to consider sex-biased developmental effects of EDCs.
Frequency combs have become a prominent research area in optics. Of particular interest as integrated comb technology are chip-scale sources, such as semiconductor lasers and microresonators, which ...consist of resonators embedding a nonlinear medium either with or without population inversion. Such active and passive cavities were so far treated distinctly. Here we propose a formal unification by introducing a general equation that describes both types of cavities. The equation also captures the physics of a hybrid device-a semiconductor ring laser with an external optical drive-in which we show the existence of temporal solitons, previously identified only in microresonators, thanks to symmetry breaking and self-localization phenomena typical of spatially extended dissipative systems.
Three-dimensional (3D) printing is a recent technology, which gives the possibility to manufacture personalised dosage forms and it has a broad range of applications. One of the most developed, it is ...the manufacture of oral solid dosage and the four 3DP techniques which have been more used for their manufacture are FDM, inkjet 3DP, SLA and SLS. This systematic review is carried out to statistically analyze the current 3DP techniques employed in manufacturing oral solid formulations and assess the recent trends of this new technology. The work has been organised into four steps, (1) screening of the articles, definition of the inclusion and exclusion criteria and classification of the articles in the two main groups (included/excluded); (2) quantification and characterisation of the included articles; (3) evaluation of the validity of data and data extraction process; (4) data analysis, discussion, and conclusion to define which technique offers the best properties to be applied in the manufacture of oral solid formulations. It has been observed that with SLS 3DP technique, all the characterisation tests required by the BP (drug content, drug dissolution profile, hardness, friability, disintegration time and uniformity of weight) have been performed in the majority of articles, except for the friability test. However, it is not possible to define which of the four 3DP techniques is the most suitable for the manufacture of oral solid formulations, because the selection is affected by different parameters, such as the type of formulation, the physical-mechanical properties to achieve. Moreover, each technique has its specific advantages and disadvantages, such as for FDM the biggest challenge is the degradation of the drug, due to high printing temperature process or for SLA is the toxicity of the carcinogenic risk of the photopolymerising material.
We experimentally demonstrate the existence of nondispersive solitary waves associated with a 2π phase rotation in a strongly multimode ring semiconductor laser with coherent forcing. Similarly to ...Bloch domain walls, such structures host a chiral charge. The numerical simulations based on a set of effective Maxwell-Bloch equations support the experimental evidence that only one sign of chiral charge is stable, which strongly affects the motion of the phase solitons. Furthermore, the reduction of the model to a modified Ginzburg-Landau equation with forcing demonstrates the generality of these phenomena and exposes the impact of the lack of parity symmetry in propagative optical systems.
We study the time dependence of the optical power emitted by terahertz and mid-IR quantum cascade lasers in presence of optical reinjection and demonstrate unprecedented continuous wave (CW) emission ...stability for strong feedback. We show that the absence of coherence collapse or other CW instabilities typical of diode lasers is inherently associated with the high value of the photon to carrier lifetime ratio and the negligible linewidth enhancement factor of quantum cascade lasers.
Used as alternative energy sources, solid biofuels have the advantage of simultaneously reduce fossil fuel dependence and mitigate climate changes by reducing greenhouse gas emissions. Biomass ...storage and handling play a key role for wood fuel quality assessment: in particular, the presence of covering systems influences biomass drying process and factors leading to bulk compaction (e.g. reduced particle size) negatively affect woody biomass preservation till final use. To study the effect that particle size and covering have on biofuel quality, Short Rotation Forestry (SRF) poplar trees were harvested and chipped by means of a Claas Jaguar 890 operating machine equipped with a “GBE-1” header for SRF. The chipping procedure was carried out in March 2009 using on the same header both the standard chipping drum and a special on purpose drum designed by CRA-ING to obtain coarser particles. The chipped biomass was subsequently stored in stacks on a paved surface for a 120 days period to evaluate: i) effect of particle size on uncovered stacks drying dynamic and fuel quality, ii) effect of the presence of non-woven tarp on drying and fuel quality of biomasses standardly chipped with the conventional drum. Coarser stack was found to have a less prompt dehydration and, at the end of the storage period, have less energy and dry matter loss. In case of biomass chipped with the conventional drum, at the end of the storage period the effect of covering ended up in wood fuel with significantly higher heating value.
•Poplar wood from SRF was harvested and chopped with different particle size.•Biomass was organized into cone shaped stacks equipped with temperature probes.•The effect of particle size and non-woven covering was monitored for 120 days of storage.•In uncovered stacks, coarser wood chip stacks showed minor dry matter losses.•At constant particle size, covering turns out in higher lower calorific value of the biomass.
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