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There have been a growing number of treatment options available for men with metastatic castration-sensitive prostate cancer. Not only have newer agents entered the clinical landscape, there is a trend toward treatment intensification by combining multiple agents simultaneously. We aim to assess the best contemporary treatment option for men with mCSPC.We perform an updated systematic review and network meta-analysis of randomized control trials that evaluated systemic therapies in men with castration-sensitive prostate cancer. We searched multiple databases up to April 2022. We included all randomized trials assessing the effect of systemic agents. We performed subgroup analyses based on disease volume and timing of presentation. Statistical analysis was performed with Bayesian methods.We found 10 eligible trials with 10,065 patients who were included in this analysis. Triplet therapy with darolutamide or abiraterone with docetaxel and ADT improved overall survival. In the sensitivity analysis, the respective hazard ratios for triplet therapy was HR 0.70 (95%CI 0.61-0.80) compared to docetaxel+ADT and 0.77 (95%CI 0.65-0.91) compared to androgen receptor pathway inhibitors+ADT combinations. It was estimated that there was 96% chance that one of the triplet therapy combinations were the best treatment option from an OS perspective. Triplet therapy also improved progression-free survival. These benefits were pronounced in men with high-volume disease burden and those with de novo metastatic disease.The finding suggest that triplet therapy is likely the most efficacious available option in men with metastatic, castration-sensitive prostate cancer, especially in those with high-volume disease burden.

In this study, the tensile tests of Sn-0.3Ag-0.7Cu-xMn composite solder alloys were carried out at strain rates of 1 × 10 −4 s −1 , 1 × 10 −3 s −1 , and 1 × 10 −2 s −1 over a range of test temperatures of 20 °C, 60 °C, and 120 °C. The tensile tests of Cu/Sn-0.3Ag-0.7Cu-xMn/Cu solder joints aged at 150 °C for 0, 144, 288, 576, 864, and 1152 h were conducted under a strain rate of 1 × 10 −3 s −1 at 20 °C. Scanning electron microscope (SEM) was used to observe the fracture surfaces of solder alloys and joints. Results show that the Mn-containing solder alloys and joints have higher ultimate tensile strength (UTS) than Mn-free due to the effect of particle hardening. The UTS of Sn-0.3Ag-0.7Cu-xMn composite solder alloys has a logarithmic relation with strain rate and decreases with an increase of test temperature. The tensile strengths of both Sn-0.3Ag-0.7Cu-xMn solder alloy and solder joints reach the highest value when 0.1 wt.% Mn nanoparticles is added. With an increase in aging time, the tensile strength of all solder joints shows a decreasing trend as the interfacial intermetallic compound (IMC) layer becomes thicker and thicker. This results in the fracture mode of the solder joint gradually changing from the initial ductile fracture in the solder joints into the mixed fracture mode of both the ductile and the brittle fracture, and finally to the brittle fracture mode along interface IMC.

The influence of TiO2 nanoparticles on the growth of intermetallic compound (IMC) between Sn–3.0 wt% Ag–0.5 wt% Cu–x wt% TiO2 (x = 0, 0.02, 0.05, 0.1, 0.3, and 0.6) composite solder and the Cu substrate during isothermal aging process at temperatures of 120, 150, and 190 °C has been investigated in this study. Scanning electron microscopy was used to observe the microstructural evolution of the solder joints and measure the thickness of IMC layer. The IMC phases were identified by energy-dispersive X-ray spectroscopy and X-ray diffractometry. Results show that two intermetallic layers, Cu6Sn5 and Cu3Sn phase are formed at the interface and the morphology of the Cu6Sn5 phase transforms from scallop-type to layer-type in Sn–3.0Ag–0.5Cu–xTiO2 solder joints. The addition of nano-TiO2 has a strong influence on the growth of overall IMC layers, and the thickness of overall IMC layers rapidly increase with aging temperature and time. The growth rates and activation energies of the IMC growth of six solder alloys were determined. Results reveal that, for three different ageing temperatures, the growth rates of overall IMC layers decrease with an increase in nano-TiO2 proportion. The activation energies for the growth of overall IMC layers range from 48.34 to 63.61 kJ/mol. Adding nano-TiO2 to Sn–3.0Ag–0.5Cu solder could evidently increase the activation energy of overall IMC layers, reduce the atomic interdiffusion rate, and thus inhibit excessive growth of overall IMC layers.

The influence of TiO 2 nanoparticles on the growth kinetics of intermetallic compound (IMC) between Sn–3.0 wt.% Ag–0.5 wt.% Cu– x wt.%TiO 2 ( x = 0, 0.02, 0.05, 0.1, 0.3, and 0.6) solder and copper substrate during reflow process has been investigated in this study. Scanning electron microscope (SEM) was applied to observe the microstructural evolution of the solder joints, to measure the thickness of the IMC layer, and to estimate the grain size of the IMC layer. The IMC phases were identified by energy-dispersive X-ray spectroscopy (EDX) and X-ray diffractometry (XRD). Results show that both the thickness and grain size of IMC decrease when TiO 2 nanoparticles are added into the Sn–3.0Ag–0.5Cu solder system, and have a significant drop when the weight percentage of TiO 2 nanoparticles is about 0.1 wt.%. Beyond this amount, the thickness and grain size of IMC increase slightly. The growth exponents for both the IMC layers and grains are determined by curve-fitting to study the growth kinetics of IMC in the soldering reaction process. Results reveal that the growth exponents of the IMC layer range from 0.354 to 0.358, and those of the IMC grains range from 0.332 to 0.346, which suggests that the growth of the IMC layer is controlled by the combined kinetics process of atomic interdiffusion, interfacial reaction, and grain ripening. These data also show that Sn–3.0Ag–0.5Cu with about 0.1 wt.% TiO 2 nanoparticles solder system exhibits the smallest growth rate and gives the most prominent effect in suppressing IMC growth and refining IMC grain size. Based on the theory of adsorption, heterogeneous nucleation, and Ostwald ripening, a mechanism for retarding the IMC growth rate due to TiO 2 nanoparticles addition is proposed.

The influence of TiO2 nanoparticles on thermal property, wettability, and interfacial reaction in Sn–3.0Ag–0.5Cu–xTiO2 (x = 0, 0.05, 0.1, and 0.6) lead-free composite solder was investigated in this study. Results show that the solidus temperatures of the TiO2-containing composite solder have no obvious change compared with TiO2-free solder. However, the liquidus temperatures of the TiO2-containing composite solders increase by 4.4 °C with an increase in amounts of TiO2 nanoparticles. The wetting angle of the composite solder decreases with the addition of TiO2 nanoparticles ranging from 0.05 to 0.1 wt%, while the spreading area increases. Based on the spherical cap model, the mathematical relation between the wetting angle and spreading area is analyzed. Scanning electron microscopy was used to observe the interfacial microstructure evolution of solder joints and to estimate the thickness of the intermetallic layer. Energy dispersive x-ray and x-ray diffractometry were used to identify the intermetallic compound (IMC) phases. Results reveal that both the thickness of IMCs and the size of Cu6Sn5 grains formed in the solder matrix decrease when TiO2 nanoparticles were added. It was also observed that some of the TiO2 nanoparticles are adsorbed on the surfaces of the scallop-like Cu6Sn5 grains. According to the adsorption theory, the surface energy of the Cu6Sn5 grains decreases with adsorption of TiO2 nanoparticles. Therefore, the diffusion of Sn and Cu atoms might be retarded, resulting in suppressing the growth of the IMCs layer.

We review recent advances in fast algorithms for fast integral equation solvers that are useful for IC applications. We review fast solvers for Laplace's equation, which is about 10 times faster than the conventional fast multipole method. Then we review the physics of low-frequency electromagnetics, and the relevant low-frequency method of moments. We describe a fast solver that allows us to solve over one million unknowns on a workstation recently. In addition, we demonstrate the applications of these fast integral equation solvers to the lithography problem. In addition, we propose a scheme whereby we first characterize blocks of linear circuits with network S, Y, or Z parameters. Then a fast real-time convolution scheme is used to calculate the interaction of a linear circuit with nonlinear terminations such as transistors and diodes. Such a scheme requires no model-order reduction of the circuits.

This paper gives an overview of computational electromagnetics for simulating complex structures with a large number of unknowns using integral equation method. First, it discusses the pros and cons of differential equation solvers versus integral equation solvers. Then it gives an overview of different fast algorithms for solving integral equations. It also discusses the difficulty of solving electromagnetic problems in the “twilight zone” between static and full-wave electromagnetics. Finally, it discusses various methods for fast solutions of scattering and coupling problems involving layered media both for statics and dynamic problems, and presents some numerical results. To cite this article: W.C. Chew et al., C. R. Physique 6 (2005).

The stratified medium fast multipole algorithm (SMFMA) is a fast integral equation method designed for static electromagnetic coupling analysis, such as capacitance extractions. In it the multipole translators are intensively employed to account for the interactions between source and field. However, the multipole translators do not have closed forms in the presence of the multilayer medium. Numerical integrations were used to compute them, which were time consuming. In this paper, the closed forms of the multipole translators are derived by extending the spherical harmonic functions into the complex plane. Using DCIM and combining the complex images of each real image from the multilayer medium, the outgoing to local multipole translator computation can be significantly shortened. One to two orders speedup can be easily achieved with very good accuracy.

This paper reviews the recent progress of fast integral equation solvers at the Center for Computational Electromagnetics and Electromagnetics laboratory, University of Illinois at Urbana-Champaign. We will demonstrate the ability to solve a variety of electromagnetic problems for complex structures and low-frequency structures as well as large scale scattering problems with over 10 million unknowns.

An efficient static fast-multipole-method (FMM)-based algorithm is presented in this paper for the evaluation of the parasitic capacitance of three-dimensional microstrip signal lines above stratified dielectric media. The effect of dielectric interfaces on the capacitance matrix is included in the stage of FMM when outgoing multipole expansions are used to form local multipole expansions by the use of interpolated image outgoing-to-local multipole translation functions. The increase in computation time and memory usage, compared to the free-space case, is, therefore, small. The algorithm retains O(N) computational and memory complexity of the free-space FMM, where N is the number of conductor patches.

Residual stresses in dissimilar metal joints of copper and aluminium alloys have been measured using an X-ray diffraction technique and estimated by finite element analysis. The effects of local tensile and com pressive residual stresses in the joints on corrosion in artificial seawater have been investigated, using a potentiodynamic polarisation method. Galvanic cor rosion at the dissimilar metal weld region may be enhanced by the additional effect of differential stress induced by welding.

The oxidation behavior of Ni3Al alloys with zirconium additions was studied after long-term air exposure over a temperature range of 560–1300°C. The results showed that the penetration of oxides into Ni3AlZr alloys along the grain boundaries was caused by the formation of ZrO2. The penetration depth of the oxides increased with an increase of the zirconium content and oxidation temperature. The reaction of the oxides was controlled by oxygen diffusion in allotropic ZrO2, and the lines in the Arrhenius diagram of the reaction rate constants reflected at 1050°C. However, the penetration of oxides was not seen in the alloy without zirconium addition. Through electron probe microanalysis and X-ray diffraction, the compositions and structures of the oxides for these alloys were also determined.

Genes such as the Heart Fatty Acid-Binding Protein (H-FABP), the Melanocortin-4 Receptor (MC4R) and the Adipocyte Determination and Differentiation factor-1 (ADD1) play an important role in meat quality in pigs. The Meishan is one of the most prolific pig breeds in the world, but it is in danger, in China, of being replaced by other exotic pig breeds because of its slow growth rate and high body fat content. To know their present genetic status, the polymorphism of the three genes in the Meishan and four other pig populations (Sutai, Yorkshire×Sutai, Landrace×Sutai and Duroc×Landrace×Yorkshire) in China was analysed, using PCR-RFLP and PCR-SSCP, and were further compared with each other. The results showed that gene and genotype frequencies differed significantly between the Meishan and the other four populations. This is suggested to be one of the reasons for the good meat quality of the Meishan compared to the other breeds. In addition, since half of the genetic background of Sutai is from the Meishan, results also indicated that marker assisted selection (MAS) is very important for the development of new pig breeds. South African Journal of Animal Science Vol. 36(1) 2006: 1-6

Recent advances in VLSI technology heighten the need to accurately characterize three-dimensional (3D) complex interconnect structures embedded in a layered dielectric medium. Fast evaluation of the multilayer Green's function is often the key in developing an integral equation based algorithm to tackle this problem. Some of the existing pole extraction algorithms are geometry dependent. In This work we present a refined pole extraction algorithms that was conceived for finding poles in a general stratified medium at an arbitrary frequency.

Recent advances in very large scale integration (VLSI) technology heighten the need for fast and accurate calculations of the capacitance and inductance matrices of complex 3D multiconductor structures in the presence of a layered dielectric medium. A stratified medium fast multipole algorithm (SMFMA) was developed to speedup capacitance extractions for the large-number-of-unknowns case with O(N) cost (Pan, Y.C., "Development of the fast multipole method for stratified medium", Ph.D thesis, Univ. of Illinois, 2002). But in the multilayer medium, the translators and near field interactions have no closed form. Therefore, the numerical integral computation for the translator preparations makes the SMFMA setup stage very time consuming. We derive a set of identities based on extended spherical harmonic functions in the complex plane. Combined with the discrete complex image method (DCIM), the multipole translators can be represented by simple closed-form expressions. The technique can make the SMFMA setup stage one to two-orders faster compared to the old method. It provides excellent accuracy with little computation costs.

As clock rates in computers become faster, EM effects become more important in computer board and chip simulations. Hence, efficient computer simulations with the correct physics exploiting best CEM methods are imperative for the design of the next generation computers. The recently developed fast methods, MLFMA (multilevel fast multipole algorithm) and low-frequency MLFMA (LF-MLFMA), and low-frequency fast inhomogeneous plane wave algorithm (LF-FIPWA), can accelerate high-accuracy electromagnetic simulations by orders of magnitude. Such methods are integral equation methods such as MOM and low-frequency MOM (LF-MOM). LF-MLFMA/LF-MOM and LF-FIPWA/LF-MOM can be used to characterize blocks of circuits with S parameters when those parts of circuits are linear. Then we interface the nonlinear part of the circuits with the linear part with a fast convolution scheme with reduced complexity. In this manner, general circuits can be modeled by fully exploiting advances in fast electromagnetic solvers. Also, the characterization with S parameters over a broad range of frequencies can be done in parallel for different blocks of the circuit, and these parameters can be computed and stored for later simulations.

The design of a robust microprocessor requires extensive logic validation. Millions of test vectors are applied and the output of every logic node is checked against the expected output. This is largely done with RTL simulators. Such simulators ignore the analog aspects of the circuits such as power supply noise and transmission line effects. Traditionally, the analog aspects are taken into account using SPICE-like simulators to model representative cases and design for what is perceived to be the worst-case input stimulus. Alternatively, in this paper, we will present a mixed signal validation approach that comprehends both the logic and analog aspects of the circuits. We show how we applied this to the Pentium 4 processor power-up sequence validation. We will also discuss extending this approach to other disciplines such as platform and packaging.

This paper presents a refinement to the hierarchical multilayer fast multipole method (HMFMM) we developed previously (see Pan, Y.C. and Chew, W.C., Microwave Opt. Tech. Lett., vol.27, p.13-17, 2000). In HMFMM, the image outgoing-to-local multipole translator is calculated using the image theory, which requires knowledge of the location and strength of all the images. Such an approach is difficult to apply to media where three or more layers are present. We have developed a generalized approach that resolves this difficultly.

In this paper, the Fast Inhomogeneous Plane Wave Algorithm (FIPWA) for layered media is described to solve the buried object problems. The multi-level algorithm has been successfully implemented and the memory and computational complexity are shown to be O(N log N). Comparing the algorithm with the free space counterpart, it is shown that the increase of computational resource required for the buried object problems is small. Extension to a static capacitance solver as well as a broadband solver for complex structures is also illustrated.

The need to understand concrete behavior under high temperatures in the nuclear industry has become rather acute. Previously, concrete has been used in nuclear industry as inexpensive material for construction and also for radiation shielding. Presently, we are concerned with the structural integrity of the containment, subject to accidental exposure of concrete to excessively high temperatures and chemical attack. Consequently, we are now seeking basic understanding of concrete behavior at extreme environmental condition. Indispensible in mathematical modeling of concrete behavior is the constitutive relation. A constitutive model developed by Takahashi [1] has been incorporated into the coupled thermal-stress analysis code, TEMP-STRESS, which gives the stress-strain relation up to the point of cracking. This paper describes the modeling of cracking behavior. Four crack propagation criteria: the J-integral, the energy release rate, the effective strength and the failure surface criterion are examined. Several numerical examples are given. Situations under which one method might be more convenient to use than the others are discussed.

The effects of Mn content on the age hardening of Fe-Mn-Al stainless steels were examined. The Mn content varied from 23% to 36% such that after solution treatment the alloys were full austenite. After solution treatment the specimens were aged at various temperature ranging from 400°C to 900°C for one hour. It was found that peak hardness occurred at 550°C. Other specimens were then aged at 550°C for time periods ranging from 15 min. to 90 hours for the investigation of aging process. It is proposed that the strengthening effect is due to the precipitation of coherent Fe3AlCx particles if the Mn content is not too high. If the Mn content is too high (36% in this case) the precipitate was β-Mn which caused some hardening but with drastic decrease in ductility. The precipitates were examined and identified by X-ray analysis and transmission electron microscopy. The age hardening property is explained in terms of TEM microstructures.