Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) are effective as first-line treatment of advanced non-small-cell lung cancer patients with EGFR mutations (EGFR-M+).
We ...conducted a literature-based meta-analysis to quantify the magnitude of benefit with upfront EGFR TKI in EGFR-M+ patients. Meta-regression and sensitivity analyses were also carried out to identify additional predictors of outcome and to assess the influence of trial design.
Five trials (805 patients) were identified (three trials prospectively enrolling EGFR-M+ patients and two retrospective analyses of EGFR-M+ patients). TKI significantly increased progression-free survival (PFS) hazard ratio (HR) 0.45, 95% confidence interval (CI) 0.36–0.58, P < 0.0001 and overall response rate (ORR) (HR 2.08, 95% CI 1.75–2.46, P < 0.0001) over chemotherapy, while significantly decreasing neutropenia. No significant difference was observed in overall survival. The rate of exon-19 mutations, female gender, and nonsmoking status were identified as additional predictors of outcome at meta-regression analysis. A significant interaction with trial design was found for both PFS (P = 0.028) and ORR (P = 0.008), suggesting a larger advantage for patients treated within prospective trials.
In EGFR-M+ patients, first-line TKI increase both PFS and ORR by ∼25%, while significantly decreasing toxicity. The role of additional predictive factors and the influence of trial design on the magnitude of the observed benefit warrant further investigation.
The role of second-line chemotherapy (CT) is not established in advanced biliary tract cancer (aBTC). We investigated the outcome of aBTC patients treated with second-line CT and devised a prognostic ...model.
Baseline clinical and laboratory data of 300 consecutive aBTC patients were collected and association with overall survival (OS) was investigated by multivariable Cox models.
The following parameters resulted independently associated with longer OS: Eastern Cooperative Oncology Group performance status of 0 (P<0.001; hazard ratio (HR), 0.348; 95% confidence interval (CI) 0.215-0.562), CA19.9 lower than median (P=0.013; HR, 0.574; 95% CI 0.370-0.891), progression-free survival after first-line CT ≥ 6 months (P=0.027; HR, 0.633; 95% CI 0.422-0.949) and previous surgery on primary tumour (P=0.027; HR, 0.609; 95% CI 0.392-0.945). We grouped the 249 patients with complete data available into three categories according to the number of fulfilled risk factors: median OS times for good-risk (zero to one factors), intermediate-risk (two factors) and poor-risk (three to four factors) groups were 13.1, 6.6 and 3.7 months, respectively (P<0.001).
Easily available clinical and laboratory factors predict prognosis of aBTC patients undergoing second-line CT. This model allows individual patient-risk stratification and may help in treatment decision and trial design.
The resistive wall impedance of a vacuum chamber with elliptic cross section is of particular interest for circular particle accelerators as well as for undulators in free electron lasers. By using ...the electric field of a point charge and of a small dipole moving at arbitrary speed in an elliptical vacuum chamber, expressed in terms of Mathieu functions, in this paper we take into account the finite conductivity of the beam pipe walls by means of the surface impedance, and evaluate the longitudinal and transverse driving and detuning impedances for any beam velocity. We also extend the definition of the Yokoya form factors, valid in the thick wall regime, at any beam energy, and show that, in the ultra-relativistic limit, they coincide with the ones that are found in literature. The method is also extended to the multilayer vacuum chamber case. Under conditions generally satisfied with particle accelerator beam pipes, the classical transmission line theory can be used to modelling the impedance seen by a bunch in a vacuum chamber with several layers as an equivalent circuit with the same number of load impedances, giving, as result, a surface impedance that can be used in combination with the fields of the elliptic geometry to obtain the resistive wall impedance in an elliptical multilayer vacuum chamber. The results are also compared with a more time consuming 3D electromagnetic code and with solutions for known cases of circular and flat beam pipe.
The accurate calculation of the beam coupling impedance for particle accelerators is necessary to carefully assess the machine stability against impedance-driven collective effects. A first order ...evaluation of the beam coupling impedance is often done by means of analytical formulas and/or 2D numerical codes. The infinite length approximation is often used to simplify the calculation of the beam coupling impedance of accelerator elements. This is expected to be a reasonable assumption for devices whose length is greater than the transverse dimension but may be a less accurate approximation for segmented devices. In this work, we present the application of the mode matching method to the calculation of the transverse dipolar impedance of a cylindrical cavity loaded with a toroidal insert. By choosing different insert electromagnetic properties (permittivity, permeability, and conductivity) and dimensions, the model can represent a beam pipe, a thin insert, a lossy cavity, or a collimator for which the effect of the finite length is investigated. The method is successfully benchmarked against available analytical formulas, field-matching codes, and 3D commercial solvers. The proposed model allows for performing wide parametric scans and reaching accurate results, therefore becoming an essential tool for the impedance evaluation of accelerator devices.
Imaging the dome of Santa Maria del Fiore using cosmic rays Guardincerri, E; Bacon, J D; Barros, N ...
Philosophical transactions of the Royal Society of London. Series A: Mathematical, physical, and engineering sciences,
12/2018, Letnik:
377, Številka:
2137
Journal Article
Recenzirano
Odprti dostop
The dome of Santa Maria del Fiore, Florence Cathedral, was built between 1420 and 1436 by architect Filippo Brunelleschi and it is now cracking under its own weight. Engineering efforts are under way ...to model the dome's structure and reinforce it against further deterioration. According to some scholars, Brunelleschi might have built reinforcement structures into the dome itself; however, the only known reinforcement is a wood chain 7.75 m above the springing of the Cupola. Multiple scattering muon radiography is a non-destructive imaging method that can be used to image the interior of the dome's wall and therefore ascertain the layout and status of any iron substructure in it. A demonstration measurement was performed at the Los Alamos National Laboratory on a mock-up wall to show the feasibility of the work proposed, and a lightweight and modular imaging system is currently under construction. We will discuss here the results of the demonstration measurement and the potential of the proposed technique, describe the imaging system under construction and outline the plans for the measurement.This article is part of the Theo Murphy meeting issue 'Cosmic-ray muography'.
In this paper, we discuss the electromagnetic interaction between a point charge travelling inside a waveguide of elliptical cross section, and the waveguide itself. By using a convenient expansion ...of the Mathieu functions, useful in particular for treating a variety of problems in applied mathematics and physics with elliptic geometry, we first obtain the longitudinal electromagnetic field of a point charge (Green’s function) in free space in terms of elliptical coordinates. This expression allows, then, to calculate the scattered field due to the boundary conditions in our geometry. By summing the contribution of the direct or primary field and the indirect field scattered by the boundary, after a careful choice of some expansion expressions, we derive a novel formula of the longitudinal electric field, in any transverse position of the elliptical cross section, generated by the charge moving along the longitudinal axis of the waveguide. The obtained expression is represented in a closed form, it can be differentiated and integrated, it can be used to fully describe the radiation process of a particle beam travelling inside a waveguide of elliptical cross section, and it is valid for any elliptic geometry. The equations are used to evaluate the coupling impedance due to indirect space charge in case of elliptical geometry. In addition, they are useful as preliminary studies for the determination of the coupling impedance in different cases involving elliptic vacuum chambers, as, for example, the effect of the finite conductivity of the beam pipe wall or the geometrical variation of the vacuum chamber due to elliptic step transitions existing in some accelerators.
OBJECTIVE: The authors compared the community functioning of outpatients with persistent forms of schizophrenia after treatment with psychosocial occupational therapy or social skills training, with ...the latter conducted by paraprofessionals. METHOD: Eighty outpatients with persistent forms of schizophrenia were randomly assigned to receive either psychosocial occupational therapy or skills training for 12 hours weekly for 6 months, followed by 18 months of follow-up with case management in the community. Antipsychotic medication was prescribed through "doctor's choice" by psychiatrists who were blind to the psychosocial treatment assignments. RESULTS: Patients who received skills training showed significantly greater independent living skills during a 2-year follow-up of everyday community functioning. CONCLUSIONS: Skills training can be effectively conducted by paraprofessionals, with durability and generalization of the skills greater than that achieved by occupational therapists who provide their patients with psychosocial occupational therapy. (Am J Psychiatry 1998; 155:1087-1091)
Starting from the electric fields produced by a point charge and a dipole traveling inside a circular vacuum chamber, in this paper we derive a formalism for a complete set of equations that describe ...the electromagnetic fields and the longitudinal and transverse coupling impedances arising by the interaction of a beam with a perfectly conducting pipe in the case of elliptic geometry. The expressions, which are valid for any frequency and beam energy, are written in terms of expansions of Mathieu functions, allow to range from a circular geometry to the parallel plates, and show an interesting parallelism with the well-known expressions for a circular pipe. We also obtain that, under the approximation of low frequency, the formalism allows us to derive the Laslett coefficients for parallel plates, circular and elliptic beam pipe.
In particle accelerators, the beam quality can be strongly affected by the interaction with self-induced electromagnetic fields excited by the beam in the passage through the elements of the ...accelerator. The beam coupling impedance quantifies this interaction and allows predicting the stability of the dynamics of high intensity, high brilliance beams. The coupling impedance can be evaluated with finite element methods or using analytical approaches, such as field matching or mode matching. In this paper we present an application of the mode matching technique for an azimuthally uniform structure of finite length: a cylindrical cavity loaded with a toroidal slab of lossy dielectric, connected with cylindrical beam pipes. In order to take into account the finite length of the structure, with respect to the infinite length approximation, we decompose the fields in the cavity into a set of orthonormal modes. We obtain a complete set of equations using the magnetic field matching and the nonuniform convergence of the electric field on the cavity boundaries. We present benchmarks done with CST Particle Studio simulations and existing analytical formulas and codes, pointing out the effect of different material conductivities, finite length, and nonultrarelativistic particle beam velocity.
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