Construction of Windows for Pharmacokinetic Sampling

This paper describes a method for the construction of pharmacokinetic sampling windows so that they are around the $D$-optimum time points. Here we consider the situation where a pharmacokinetic (PK) study is accompanied by a dose-finding study in phase I clinical trial. The D-optimal criterion is often used to determine the optimal time for collecting blood samples so that they provide maximum information regarding the population PK parameters. However, collecting blood samples at the D-optimal time points is often difficult. Instead, the sampling time point chosen from a suitable time interval or window can ease the process. The proposed method is conceptually simple and considers the average value and standard deviation of D-optimal time points up to create sampling windows. Random time points can be chosen from these windows then to collect blood samples from the next cohort. The nonlinear random-effects model has been used to model the PK data. Also, we employ the continual reassessment method for dose allocation to the patients. Comparisons of the accuracy and precision for the PK parameter estimates obtained at the D-optimal and random time points are also presented. The results are convincing enough to suggest the proposed method as a useful tool for blood sample collection.

Simplified three-dimensional modeling method and its uncertainty analysis for adit fractures collected within short sampling windows

This study takes rock masses at the Songta Hydropower Station in Southeast China as examples to perform three-dimensional (3D) discrete fracture network (DFN) modeling. Field fracture traces are collected from four adits (PD252, PD254, PD262, and PD264) with 1.6 m high sampling windows. The relationship between 3D fracture parameters and two-dimensional collected trace information is investigated using data collected from short sampling windows. On the basis of this relationship, a simplified method is proposed to determine the 3D fracture density and disc diameter and generate 3D DFN. This method avoids the complex deduction processes of geometric fracture parameters, thereby simplifying 3D DFN modeling considerably. Although the method is developed on the basis of short-window collection, traditional data collected within a tall window are still applicable through the window dividing method. Short windows do not contain competent traces that reflect the structural information of rock masses. Therefore, errors are easily found during 3D DFN modeling. We propose a method to evaluate and reduce uncertainty effects. The uncertainties of fracture sets 1 and 2 are analyzed by increasing the sampling size in a single structural domain, and the errors are acceptable.

Citizenship and the Economic Assimilation of Canadian Immigrants

In this paper, we examine whether acquiring citizenship improves the economic assimilation of Canadian migrants. We took advantage of a natural experiment made possible through changes in the Canadian Citizenship Act of 2014, which extended the physical presence requirement for citizenship from three to four years. Using quasi-experimental methods, we found that delaying citizenship eligibility by one year adversely affected Canadian residents' wages. Access to better jobs explains a citizenship premium of 11 percent in higher wages among naturalized migrants. Our estimates are robust to model specifications, differing sampling windows to form the treatment and comparison groups, and whether the estimator is a non-parametric rather than a parametric one. We discuss how our findings are relevant to the optimal design of naturalization policies regarding efficiency and equity.

Size effect characteristics of structural surfaces by improved projective covering method

Accurate characteristic of structural surfaces roughness at the relevant scale is very important to understand mechanical properties of rock mass discontinuities. So, a systematic investigation has been carried out to understand the effect of scale on the structural surface roughness by fractal dimension method. Firstly, considering the shortcoming of the projective covering method (PCM), we improved this method based on stochastic approach. Secondly, to investigate the size effect of the structural surface roughness, we selected six sampling windows, respectively, from the central and four corners part of structural planes (2 m × 2 m). The sampling windows range from 62.5 mm × 62.5 mm to 2000 mm × 2000 mm. And then, we calculated fractal parameters of the different size surfaces using improved projective covering method (IPCM) at the same resolution. Thirdly, we discussed a new method of determining reasonable size of structural surfaces by the parameter $$\Delta D_{\max }^{SD}$$ Δ D max SD . This parameter is difference of the maximum fractal dimension of the same size structural surface in different regions. The results show that: (1) The size effect of structure surfaces is different with different morphological surface. Generally, as the size increases, the roughness of structure surfaces increases and then decreases. There is positive size effect in small scale and negative size effect in large scale. (2) For a given structural surface, when the same size surfaces are selected from different locations of the structural planes, and the size effect characteristics are also different. (3) As the size of structure surfaces increases, the parameter $$\Delta D_{\max }^{SD}$$ Δ D max SD gradually decreases and tends to almost constant. The result of this study is a useful supplement to the comprehensive understanding of the size effect of structural surfaces roughness.

A fast X-corner detection method based on block-search strategy

In order to detect X-corner (or X-point) features more accurately and apace, this article presents a novel and fast detection method based on block-by-block search strategy. Unlike general pixel-by-pixel searching method, the sampling window is first moved along the image block-by-block to find the X-corner candidates rapidly keeping in view the four-step and min-step-distance constraints. During the motion, some overlap is kept between the adjacent sampling windows in order to ensure that all X-corners could have a chance to reside inside, avoiding the possibility of that some X-corners may locate on the edge. Moreover, labeling technology is adopted to prevent duplicate candidates. After the collection of X-corner candidates, the neighborhood variance and centrosymmetry constraints are used to exclude outliers, and the intersection lines is calculated as the sub-pixel position of true X-corner. The experimental results using synthetic and real images show that the presented method approximately takes just about 13 ms to detect 52 X-corners in an image size of 1024 × 768 on a computer having Intel Core i3 CPU at 3.6 GHz and 4GB RAM. The proposed method has faster detection speed compared with the latest methods such as ChESS, SC, and Micron Tracker system while possessing the same or higher detection precision.

Role of normal boundary condition in interface shear test for the determination of skin friction along pile shaft

This paper presents numerical results from a two-dimensional discrete element method (DEM) simulation study on the influence of lateral boundary condition on shaft resistance of a pile driven into a crushable sand. The study was conducted by comparing simulation results from the pile penetration test and the interface shear test employing parallel-bonded agglomerates for modeling of the particle breakage. The interface shear test was performed under three different types of normal boundary conditions; namely, constant normal load (CNL), constant normal stiffness (CNS), and constant volume (CV) boundary conditions. For the pile penetration test, a series of sampling windows were identified on the initial ground configuration to monitor the stress–strain, volume change, and particle breakage behavior of particle groups located within the sampling windows. A detailed investigation was then undertaken by comparing the behavior of particle groups with that from the interface shear test to find out which type of normal boundary condition best describes the lateral boundary condition in the pile penetration test. It has been found that the behavior of a particle group reaches the peak state below the pile tip and the critical state after it reaches the pile shaft. The influence of normal boundary condition on the stress ratio at the critical state is not obvious. The conventional interface shear test (i.e., CNL) can provide valuable information on the determination of skin friction along the pile shaft.