Anomalous high activation energy for creep in nanostructured 3YTZP/Ni cermets

The plastic behavior of cermets based on a 3 mol% yttria-stabilized tetragonal zirconia matrix that incorporates nanometric nickel inclusions (3YTZP/n-Ni), with 2.5, 5 and 10 vol.% of nickel content, has been studied by constant load tests in compression carried out in argon atmosphere. The microstructure of these composites consists of nanometric nickel inclusions homogeneously dispersed into a fine-grained zirconia matrix (about 200 nm). The microstructural and mechanical results obtained show that the creep behavior is controlled by the zirconia matrix as in 3YTZP-based cermets with micrometric Ni inclusions (3YTZP/μ-Ni); whereas the stress exponent values are similar to those of high-purity monolithic 3YTZPs, anomalous high values of the activation energy have been measured. The ceramic/metal interface plays a crucial role for creep properties; the strong TZP/n-Ni interface matching can be at the origin of these high values of the activation energies for creep.Ministerio de Educación y Ciencia MAT2003-04199-CO

Chromospheric polarimetry through multi-line observations of the 850 nm spectral region II: A magnetic flux tube scenario

In this publication we continue the work started in Quintero Noda et al. (2017) examining this time a numerical simulation of a magnetic flux tube concentration. Our goal is to study if the physical phenomena that take place in it, in particular, the magnetic pumping, leaves a specific imprint on the examined spectral lines. We find that the profiles from the interior of the flux tube are periodically dopplershifted following an oscillation pattern that is also reflected in the amplitude of the circular polarization signals. In addition, we analyse the properties of the Stokes profiles at the edges of the flux tube discovering the presence of linear polarization signals for the Ca II lines, although they are weak with an amplitude around 0.5% of the continuum intensity. Finally, we compute the response functions to perturbations in the longitudinal field and we estimate the field strength using the weak field approximation. Our results indicate that the height of formation of the spectral lines changes during the magnetic pumping process which makes the interpretation of the inferred magnetic field strength and its evolution more difficult. These results complement those from previous works demonstrating the capabilities and limitations of the 850 nm spectrum for chromospheric Zeeman polarimetry in a very dynamic and complex atmosphere.Comment: 12 pages, 12 figures, 0 tables, MNRAS main journal publicatio

Randomized Phase II Trial of Sapanisertib ± TAK-117 vs. Everolimus in Patients With Advanced Renal Cell Carcinoma After VEGF-Targeted Therapy

MTOR inhibitors; Everolimus; Renal cell carcinomaInhibidores de MTOR; Everolimus; Carcinoma de células renalesInhibidors de MTOR; Everolimus; Carcinoma de cèl·lules renalsBackground Sapanisertib, a dual mTORC1/2 inhibitor, may offer more complete inhibition of the PI3K/AKT/mTOR pathway than mTORC1 inhibitors, such as everolimus. This phase II study evaluated the efficacy and safety of single-agent sapanisertib and sapanisertib plus the PI3Kα inhibitor TAK-117, vs. everolimus in patients with advanced clear cell renal cell carcinoma (ccRCC) that had progressed on or after VEGF-targeted therapy. Materials and Methods Patients with histologically confirmed, advanced ccRCC were randomized 1:1:1 to receive single-agent everolimus 10 mg once daily, single-agent sapanisertib 30 mg once weekly, or sapanisertib 4 mg plus TAK-117 200 mg, both once daily for 3 days/week, in 28-day cycles. The primary endpoint was progression-free survival (PFS). Results Ninety-five patients were treated with everolimus or sapanisertib (n = 32 each), or sapanisertib plus TAK-117 (n = 31). There were no significant differences in PFS among the 3 groups or across any subgroups. Median PFS was 3.8 months with everolimus vs. 3.6 months with sapanisertib (HR, 1.33; 95% CI, 0.75-2.36), and 3.1 months with sapanisertib plus TAK-117 (HR, 1.37; 95% CI, 0.75-2.52). No significant differences in overall survival were seen among groups. Overall response rate was 16.7%, 0%, and 7.1%, respectively. Discontinuations due to treatment-emergent adverse events were 15.6%, 28.1%, and 29.0%. Conclusion Sapanisertib with or without TAK-117 was less tolerable and did not improve efficacy vs. everolimus in patients with advanced ccRCC who had relapsed after or were refractory to VEGF-targeted therapies. Dual mTORC1/2 inhibition may not be an effective therapeutic approach for these patients.This article is supported by Takeda Development Center Americas, Inc., Lexington, MA, USA

Chromospheric polarimetry through multi-line observations of the 850 nm spectral region III: Chromospheric jets driven by twisted magnetic fields

We investigate the diagnostic potential of the spectral lines at 850 nm for understanding the magnetism of the lower atmosphere. For that purpose, we use a newly developed 3D simulation of a chromospheric jet to check the sensitivity of the spectral lines to this phenomenon as well as our ability to infer the atmospheric information through spectropolarimetric inversions of noisy synthetic data. We start comparing the benefits of inverting the entire spectrum at 850 nm versus only the Ca II 8542 A spectral line. We found a better match of the input atmosphere for the former case, mainly at lower heights. However, the results at higher layers were not accurate. After several tests, we determined that we need to weight more the chromospheric lines than the photospheric ones in the computation of the goodness of the fit. The new inversion configuration allows us to obtain better fits and consequently more accurate physical parameters. Therefore, to extract the most from multi-line inversions, a proper set of weights needs to be estimated. Besides that, we conclude again that the lines at 850 nm, or a similar arrangement with Ca II 8542 A plus Zeeman sensitive photospheric lines, poses the best observing configuration for examining the thermal and magnetic properties of the lower solar atmosphere.Comment: 14 pages, 11 figure

Grade 3/4 Adverse Event Costs of Immuno-oncology Combination Therapies for Previously Untreated Advanced Renal Cell Carcinoma

Advanced renal cell carcinoma; Adverse event cost; Nivolumab plus cabozantinibCarcinoma de células renales avanzado; Coste de eventos adversos; Nivolumab más cabozantinibCarcinoma de cèl·lules renals avançat; Cost d'esdeveniments adversos; Nivolumab més cabozantinibBackground Despite 4 approved combination regimens in the first-line setting for advanced renal cell carcinoma (aRCC), adverse event (AE) costs data are lacking. Materials and Methods A descriptive analysis on 2 AE cost comparisons was conducted using patient-level data for the nivolumab-based therapies and published data for the pembrolizumab-based therapies. First, grade 3/4 AE costs were compared between nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + axitinib using data from the CheckMate 214 (median follow-up [mFU]: 13.1 months), CheckMate 9ER (mFU: 12.8 months), and KEYNOTE-426 (mFU: 12.8 months) trials, respectively. Second, grade 3/4 AE costs were compared between nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + lenvatinib using data from the CheckMate 214 (mFU: 26.7 months), CheckMate 9ER (mFU: 23.5 months), and KEYNOTE-581 (mFU: 26.6 months) trials, respectively. Per-patient costs for all-cause and treatment-related grade 3/4 AEs with corresponding any-grade AE rates ≥ 20% were calculated based on the Healthcare Cost and Utilization Project database and inflated to 2020 US dollars. Results Per-patient all-cause grade 3/4 AE costs for nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + axitinib were $2703 vs.$4508 vs. $5772, and treatment-related grade 3/4 AE costs were$741 vs. $2722 vs.$4440 over ~12.8 months of FU. For nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + lenvatinib, per-patient all-cause grade 3/4 AE costs were $3120 vs.$5800 vs. $9285, while treatment-related grade 3/4 AE costs were$863 vs. $3162 vs.$5030 over ~26.6 months of FU. Conclusion Patients with aRCC treated with first-line nivolumab-based therapies had lower grade 3/4 all-cause and treatment-related AE costs than pembrolizumab-based therapies, suggesting a more favorable cost-benefit profile.This study was funded by Bristol Myers Squibb

Temporal Trends in Grade 3/4 Adverse Events and Associated Costs of Nivolumab Plus Cabozantinib Versus Sunitinib for Previously Untreated Advanced Renal Cell Carcinoma

Advanced Renal Cell Carcinoma; Adverse Events; NivolumabCarcinoma de células renales avanzado; Eventos adversos; NivolumabCarcinoma de cèl·lules renals avançat; Esdeveniments adversos; NivolumabBackground and Objectives Novel immunotherapy-based combination treatments have drastically improved clinical outcomes for previously untreated patients with advanced/metastatic renal cell carcinoma (aRCC). This study aimed to assess the temporal trends in grade 3/4 adverse event (AE) rates and associated costs of nivolumab plus cabozantinib combination therapy versus sunitinib monotherapy in previously untreated patients with aRCC. Methods Individual patient data from the CheckMate 9ER trial (nivolumab plus cabozantinib: N = 320; sunitinib: N = 320) were used to calculate the proportion of patients experiencing grade 3/4 AEs. AE unit costs were obtained from the United States (US) 2017 Healthcare Cost and Utilization Project (HCUP) and inflated to 2020 US dollars. Per-patient-per-month (PPPM) all-cause and treatment-related grade 3/4 AE costs over 18-months, temporal trends, and top drivers of AE costs were evaluated in both treatment arms. Results Overall, the proportion of patients experiencing grade 3/4 AEs decreased over time, with the highest rates observed in the first 3 months for the nivolumab plus cabozantinib and sunitinib arms. Compared with sunitinib, nivolumab plus cabozantinib was associated with consistently lower average all-cause AE costs PPPM [month 3: $2021 vs.$3097 (p 0.05); month 18: $1337 vs.$1755 (p > 0.05)]. Over 18 months, metabolism and nutrition disorders ($244), laboratory abnormalities ($182), and general disorders and administration site conditions ($122) were the costliest all-cause PPPM AE categories in the nivolumab plus cabozantinib arm, and laboratory abnormalities ($443), blood and lymphatic system disorders ($254), and metabolism and nutrition disorders ($177) were the costliest in the sunitinib arm. Trends of treatment-related AE costs were consistent with all-cause AE costs. Conclusions Nivolumab plus cabozantinib was associated with lower costs of grade 3/4 AE management PPPM than sunitinib, which accumulated over the 18-month study period

Defensive Strategy and Player Sex Impact Heart-Rate Responses During Games-Based Drills in Professional Basketball

[EN] Purpose: Games-based drills (GBD) are the predominant form of training stimulus prescribed to male and female basketball players. Despite being readily manipulated during GBD, the impact of defensive strategy on the sex-specific demands of GBD remains unknown. Therefore, the aim of this study was to quantify and compare the heart-rate (HR) responses experienced during 5v5 GBD using different defensive strategies (man-to-man defense vs zone defense [ZD] formations) according to player sex. Method: HR was recorded in 11 professional male and 10 professional female basketball players while performing 5v5 GBD with different defensive strategies (man-to-man defense or ZD). HR-based training load was also calculated using the summated heart-rate zones model. Results: During man-to-man defense, mean HR (η2p = .02), relative time (in percentage) spent working at 90% to 100% maximal HR (η2p = .03), and summated heart-rate zones (η2p = .02) were greater (P < .05) in female players compared with males. During ZD, higher (P < .01) peak HR (η2p = .07), mean HR (η2p = .11), relative and absolute (in minutes) time spent working at 80% to 89% maximal HR (η2p = .03 and .03, respectively) and 90% to 100% maximal HR (η2p = .12 and .09, respectively), and summated heart-rate zones (η2p = .19) were observed in female players compared with males. Conclusions: The defensive strategy employed during 5v5 full-court GBD influences HR responses and training load differently according to sex, where female players experience higher HR responses than males, especially when ZD are adopted. Basketball coaching staff can use these findings for the precise manipulation of team defenses during GBD to elicit desired cardiovascular stress on players

Bose-Einstein condensate dark matter phase transition from finite temperature symmetry breaking of Klein-Gordon fields

In this paper the thermal evolution of scalar field dark matter particles at finite cosmological temperatures is studied. Starting with a real scalar field in a thermal bath and using the one loop quantum corrections potential, we rewrite Klein-Gordon's (KG) equation in its hydrodynamical representation and study the phase transition of this scalar field due to a Z_2 symmetry breaking of its potential. A very general version of a nonlinear Schr\"odinger equation is obtained. When introducing Madelung's representation, the continuity and momentum equations for a non-ideal SFDM fluid are formulated, and the cosmological scenario with the SFDM described in analogy to an imperfect fluid is then considered where dissipative contributions are obtained in a natural way.Additional terms appear compared to those obtained in the classical version commonly used to describe the \LambdaCDM model, i.e., the ideal fluid. The equations and parameters that characterize the physical properties of the system such as its energy, momentum and viscous flow are related to the temperature of the system, scale factor, Hubble's expansion parameter and the matter energy density. Finally, some details on how galaxy halos and smaller structures might be able to form by condensation of this SF are given.Comment: Substantial changes have been made to the paper, following the referees recommendations. 16 pages. Published in Classical and Quantum Gravit

Moving Magnetic Features around a Pore

Spectropolarimetric observations from Sunrise II/IMaX obtained in June 2013 are used for a statistical analysis to determine the physical properties of moving magnetic features (MMFs) observed near a pore. MMFs of the same and opposite polarity with respect to the pore are found to stream from its border at an average speed of 1.3 km s$^{-1}$ and 1.2 km s$^{-1}$ respectively, with mainly same-polarity MMFs found further away from the pore. MMFs of both polarities are found to harbor rather weak, inclined magnetic fields. Opposite-polarity MMFs are blue-shifted, while same-polarity MMFs do not show any preference for up- or downflows. Most of the MMFs are found to be of sub-arcsecond size and carry a mean flux of $\sim$ 1.2$\times 10^{17}$ Mx.Comment: 8 pages, 4 figures, accepted for publication in ApJ

Maximum Entropy Limit of Small-scale Magnetic Field Fluctuations in the Quiet Sun

The observed magnetic field on the solar surface is characterized by a very complex spatial and temporal behavior. Although feature-tracking algorithms have allowed us to deepen our understanding of this behavior, subjectivity plays an important role in the identification and tracking of such features. In this paper, we continue studies Gorobets, A. Y., Borrero, J. M., & Berdyugina, S. 2016, ApJL, 825, L18 of the temporal stochasticity of the magnetic field on the solar surface without relying either on the concept of magnetic features or on subjective assumptions about their identification and interaction. We propose a data analysis method to quantify fluctuations of the line-of-sight magnetic field by means of reducing the temporal field's evolution to the regular Markov process. We build a representative model of fluctuations converging to the unique stationary (equilibrium) distribution in the long time limit with maximum entropy. We obtained different rates of convergence to the equilibrium at fixed noise cutoff for two sets of data. This indicates a strong influence of the data spatial resolution and mixing-polarity fluctuations on the relaxation process. The analysis is applied to observations of magnetic fields of the relatively quiet areas around an active region carried out during the second flight of the Sunrise/IMaX and quiet Sun areas at the disk center from the Helioseismic and Magnetic Imager on board the Solar Dynamics Observatory satellite.Comment: 11 pages, 5 figures, The Astrophysical Journal Supplement Series (accepted