**Author details**

George Tokmaji1 , Berto J. Bouma2 , Dave R. Koolbergen1,3 and Bas A.J.M. de Mol1

1 Department of Cardiothoracic Surgery, Academic Medical Center, Amsterdam, The Neth‐ erlands

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2 Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands

3 Department of Cardiothoracic Surgery, Leiden University Medical Center, Leiden, The Netherlands


**6.2 Tight oil reservoir**

The tight oil reservoir is a type of unconventional oil reservoir that is hard to produce due to the low permeability. In recent years, the exploitation of tight oil reservoir increased due to advanced technologies in the production industry and high demand for the energy. Two main technologies that need to be increased are horizontal drilling and multi-stage hydraulic fracturing. U.S. Energy Information Administration reported that tight oil production will increase from 33% of total lower 48 onshore oil production to 51% in 2040 [59, 60]. However, the decline curves of primary production are steep due to low permeability [60, 66]. CO2- EOR is utilized more commonly as compared to water flooding in case of tight oil reservoirs due to the poor sweep efficiency of water flooding and low injectivity of water in tight oil reservoirs. Moreover, in case of the reservoirs with a higher wetting tendency toward oil (oil-wet), water flooding would be less effective. CO2-EOR could be implemented as continuous CO2 injection or huff and puff technique. Hydraulic fracturing is one of the most important mechanisms in recoveries from tight oil reservoirs. The geometry, the number, and the spacing of the fracture can affect the recovery from the tight oil reservoirs. Bakken reservoir in the US is one of the largest unconventional tight oil reservoirs that has been produced since early 1950s. Through years of production and study of the reservoir, engineers decided that the following strategies are suitable for this field as shown in **Table 2**.

The followings outcomes were observed during the simulation of CO2-EOR for the period of 30 years on Bakken Field:


**1. Introduction**

Recently, with widespread use of smartphones, location-based services (LBS) have gained increasing public attention [1,2]. Navigation and route guidance applications that use GPS are the most representative LBS. In addition, LBS for pedestrians, such as surrounding information search services and evacuation route guidance in the event of a disaster, are currently being actively provided. An indoor localization system is an important technology for providing LBS. This enables the estimation of the location of people in a space in which GPS signals are not provided.

Typical mechanisms for indoor localization use wireless signals or inertial measurement units (IMU). Trilateration, triangulation, and fingerprinting methods using the received signal strength indication (RSSI) or channel state information (CSI) have been widely studied in wireless signal-based indoor localization systems. These methods mainly use radio technologies, such as Wi-Fi, Bluetooth, ZigBee, and ultra-wideband (UWB). The wireless signal-based system can operate only in a space with installed infrastructure. In addition, it is difficult to obtain consistent positioning accuracy because the radio signal is greatly affected by nearby obstacles (e.g., walls, columns, and objects) or interference signals. Indoor localization techniques through trilateration and triangulation calculate the position of the target by measuring the distance or angle between the three coordinates that serve as reference points and the tag that serves as the target [3]. In the case of using Wi-Fi as a radio signal, to measure the distance between the access point (AP) and the tag for transmitting the wireless Wi-Fi signal, the RSSI values are converted into distance information or the time of arrival (ToA), and the location is calculated using triangulation. Indoor localization technology through triangulation uses the angle at which radio signals arrive, i.e., angle of arrival (AoA). Mohammed et al. [4] addressed this problem by identifying the condition of an undetected direct path (UDP), which is a straight path from the transmitter to the receiver and introducing a deep learning model to mitigate it. Michael et al. [5] implemented a more accurate time difference of arrival (TDoA) based

**Citation:** Yoon, J.; Kim, S. Practical and Accurate Indoor Localization System Using Deep Learning. *Sensors* **2022**, *22*, 6764. https://doi.org/ 10.3390/s22186764

Academic Editors: Hugo Gamboa, Tanja Schultz and Hui Liu

Received: 29 July 2022 Accepted: 5 September 2022 Published: 7 September 2022

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

indoor position recognition technology through multiband (UWB-wideband) UWB technology and a single-input multiple-output (SIMO) method to address the problem of multipath attenuation of radio signals. Shuai et al. [6] proposed enhanced trilateration localization, which improves localization accuracy through quality evaluation and adaptive selection (IT-QEAS). First, they assess the quality of the distance measurement results among the anchor nodes and select the anchor nodes that have the highest quality. Then, a localization calculation was performed with the selected anchor node. However, although indoor localization systems using triangulation and trilateration have improved through various studies, the use of RSSI or CSI is affected by the irregular signal attenuation characteristics of the radio signal depending on the surrounding environment. In addition, because wireless signals are used, APs for transmitting wireless signals must be preinstalled, and there is a possibility of blind spots that radio signals cannot reach, or that radio signals are blocked by obstacles or walls. In particular, localization solutions that need pre-installation in the infrastructure have reduced practicality.

The fingerprinting method divides the service area into several cells, selects a reference location, and receives a wireless signal sent by the Wi-Fi AP at each cell through a smartphone to measure the RSSI values and create a radio map based on it. Subsequently, the user receives a signal from the AP at a random location, measures the RSSI value, contrasts it with a radio map, and estimates the corresponding cell as the user's location. Yuanchao et al. [7] proposed GradIentFingerprintTing (GIFT) to reduce instability in RSSI values that change over time in indoor environments. Qianwen et al. [8] implemented fingerprinting technology using CSI rather than RSSI and introduced a K-nearest neighbor (KNN) algorithm to increase the accuracy of the final indoor position calculation. Unlike traditional algorithms, Minh et al. [9] introduced a recurrent neural network (RNN) model instead of finding the position of the user one at a time, reducing the instability of the RSSI values that change over time. However, the precise indoor localization of fingerprinting requires a lot of information about the reference locations, that is, cells, used for positioning and the process of collecting RSSI from cells requires service providers to collect them, which is costly. Furthermore, the RSSI value also varies with changes in the surrounding environment as radio maps are pre-written, making it essential to calibrate radio maps over time, and it is impossible to accurately measure RSSI owing to the attenuation of signals caused by interference from adjacent channels. In a relatively static situation, an indoor localization system using fingerprinting can achieve high performance. However, if there are many people and the surrounding environment is very dynamic, it is difficult to expect accuracy because fingerprinting may be hard to implement.

Pedestrian dead reckoning (PDR) is a representative indoor localization method that uses IMU. This uses collected sensor values, such as accelerometers, magnetometers, barometers, and gyroscopes, to estimate the moving distance and direction of movement of people. The positioning accuracy of the PDR is mainly determined by a model or formula that converts the sensor value into moving distance and direction. Various PDR techniques [10–14] have been studied, and they exhibit a position error of several centimeters. However, the models of formulas derived from conventional studies are difficult to generalize under various conditions (e.g., moving patterns, sensor placements, and the surrounding environment). They operate only under specific conditions; therefore, they are difficult to use in practice. PDR is a technology that calculates the next location of pedestrian using sensor data, such as accelerometers, gyroscopes, and magnetometers, from the previous location. The next position of the pedestrian is estimated by estimating the number of steps and stride of pedestrians through acceleration sensors and estimating the pedestrians' orientation using a magnetometer and gyroscope. The PDR is largely divided into two areas according to how the sensor data are used to calculate the next location. First, the pattern of the data collected by the accelerometer is analyzed to calculate the number of steps. Second, the stride is estimated using the value of the accelerometer.

For example, the number of steps can be calculated using a peak detection method based on the accelerometer value of a walking pedestrian. With recent improvements in

sensor accuracy and computing power of IMU and smartphones, which are data collection devices, indoor location recognition studies using PDR show an error rate within several centimeters. Godha et al. [15] proposed a PDR system that combines GPS coordinates with sensor values obtained using inertial sensors to achieve reasonable accuracy in indoor and outdoor environments. Ionut et al. [16] introduced a practical system that uses an accelerometer and magnetometer from smartphones, without relying on the Wi-Fi's AP infrastructure, to record pedestrian walking patterns and match them with possible paths on real maps. Kang et al. [17,18] replaced inertial sensors, which are the measuring equipment used in conventional PDR methods, with smartphones to implement indoor position recognition technologies that do not require expensive additional devices or infrastructure. In addition, the number of steps was determined using the accelerometer of the smartphone, and the accuracy of the magnetometer sensor was correlated with the gyroscope to estimate the heading direction. However, it should be considered that the magnetometer sensor is not used as a major data source for estimating the direction of progress for pedestrians because it is greatly influenced by the surrounding environment.

PDR has the advantage that it does not require additional infrastructure. However, there is a significant problem with indoor localization performance, depending on the model and formula that estimates gait information with sensor data. In addition, the selection of the initial position by the user is crucial. The user's next position obtains results from the prior position, the initial position fades over time because fine errors accumulate in the collected sensor data. Another problem is that indoor localization performance varies depending on the user of the PDR system. Different users have different heights, step lengths, gait patterns, and smartphone placements, which can lead to differences in the performance of the model in estimating the moving speed and heading direction.

The other way of using sensor data to calculate the next position is by using deep learning. Deep learning is a technique for predicting the correct answer by learning patterns or characteristics from training data using models based on neural networks. Because the accelerometer data obtained from a walking person has a certain pattern, it is very suitable for applying deep learning. In other words, the accelerometer value of the pedestrian is composed of a training dataset for learning the deep learning model, and the moving speed or distance of the pedestrian is estimated using the trained deep learning model.

Gu et al. [19] proposed a deep learning-based stride estimation method that can adapt to the characteristics of various users, considering that the walking speed and arrangement state of smartphones are different for each pedestrian. After removing noise from the accelerometer and gyroscope data collected from smartphones using a low pass filter (LPF), the sensor data is trained in a supervised learning model that estimates the stride by dividing the sensor data into segments, each segment representing one step. Kang et al. [20] implemented a new technology for indoor localization, using a deep learning model that learns pedestrian walking pattern data collected outdoors. GPS coordinates and accelerometer data were collected outdoors to determine the moving speed of pedestrians using divided signal frames with hybrid multiscale convolutional recurrent neural network models. In addition, traditional PDR methods are proposed to calculate the number of steps and strides of the IMU signal in a passive way; however, in [20], the moving distance is estimated by calculating the average travel rate from the signal frame.

Although the related studies above have increased the accuracy of indoor localization by applying deep learning, the problem of whether they are practical for pedestrians remains. For example, in [19], when mapping training datasets and labels for learning deep learning models, applicants who collected training data counted their own steps, took them as the ground truth, and organized them into labels. This approach has a very impractical drawback in that the user must calculate the label (ground truth) himself and configure the training dataset until the system shows sufficient performance. To solve this problem, [20] proposed a deep learning model that learns sensor data using GPS as a label for the first time; however, only the steps walked on a straight path were evaluated without considering the orientation of pedestrians.

 In addition, smartphones include Wi-Fi, Bluetooth, and diverse sensors that are widely used for indoor localization [21–23]. In this study, we propose a smartphone-based indoor localization system using deep learning. The proposed system operates based on PDR using an accelerometer to estimate the moving speed and a game rotation vector sensor to estimate the heading direction. The data collected by the accelerometer outdoors were used as training data for the deep learning model. The moving speed of the data was labeled using the GPS value. Although the accuracy of the label information decreases owing to the inherent error of GPS, it is very practical because training data can be collected without user intervention. We propose practical solutions and techniques for increasing the positioning accuracy of unspecified smartphone users. The contributions of this study are as follows.

The remainder of this paper is organized as follows. Section 2 presents problems that have not been resolved in conventional studies. Section 3 introduces the proposed indoor localization system, and Section 4 evaluates the performance of the proposed system. Finally, conclusions are presented in Section 5.

#### **2. Problem Definition**

We studied a PDR-based indoor localization using deep learning. In this section, we describe three major problems of conventional PDR-based indoor localization.

#### *2.1. Low GPS Accuracy*

GPS can provide geolocation and time information to a GPS receiver if four or more line-of-sight GPS satellites exist. Using GPS values as training data labels for deep learning may improve the practicality of the indoor localization technology. However, GPS has inherent errors owing to satellite signal blockage and reflection caused by buildings, trees, etc. If the GPS receiver is located in a city center or forest, the quality of the GPS data may be poor. In this case, using GPS data as training data labels is not appropriate because unreliable labels degrade the accuracy of the deep learning models. This affects the performance of indoor localization systems.

We performed an outdoor experiment to analyze the accuracy of the GPS data using a smartphone. The subjects repeatedly moved 75 m in various environments. Figure 1 shows the distance error ratio according to the number of receivable GPS satellites used in the experiment. When the subject moves near high-rise buildings or under a bridge, the smartphone can receive between four and six GPS satellite signals. However, a high distance error ratio of 5.34% to 8.47% was seen in this signal. When the subject moved in the campus playground or field, nine or more GPS satellites could be received. In this case, the distance error ratio was very low (i.e., 0.67–1.72%) compared to the case where the number of receivable GPS satellites is small. In the experiment, we verified that unfiltered GPS data are unsuitable as training data labels for deep learning.

**Figure 1.** Distance error ratio according to the number of receivable GPS satellites.

#### *2.2. Bias of Sensor Data*

An artificial neural network [24] is a statistical learning algorithm constructed by imitating the manner in which nerve cells or neurons are inter-connected in the human brain. Just as human neurons receive and store input values through synapses from several other neurons and then export output values to the next neuron, the artificial neural network model neuron receives multiple inputs and transmits output values to the next neuron in the model. Artificial neural networks are constructed by stacking several neuron models. Deep learning is a type of machine-learning algorithm based on artificial neural networks. Deep learning has been widely used in various applications.

Deep learning refers to a learning model that predicts outcomes by extracting features or patterns from training data. The size and quality of the training data significantly influence the performance of the deep learning model. Thus, it is very important to secure a sufficient amount of high-quality data from which a deep learning model can extract features. A PDR-based indoor localization system mainly uses sensor values, such as data from accelerometers, magnetometers, barometers, and gyroscopes for training. To determine the patterns of movements in daily life, we conducted an outdoor experiment to collect data. In the experiment, a subject collected sensor values every second using a smartphone, while walking freely for 3 h. The moving speed of the subjects was obtained using GPS. Figure 2 shows the distribution of the collected data with respect to the moving speed. As a result, 66.3% of the collected data were distributed between the moving speeds 1.3 m/s and 1.7 m/s. Most of the collected data were within the average human walking speed. Since the number of samples for the speed range 1.3–1.7 m/s is much larger than that for other speeds, the data is biased. If these biased data are used for training deep earning models, it is difficult to expect high accuracy in the case the subject is not walking at an average speed. We do not need to consider data bias, if we can collect huge amounts of data. However, because collecting data is expensive, we assume that data collection is minimized.

**Figure 2.** Distribution of the collected data according to moving speed.

#### *2.3. Effect of Magentometer*

The heading direction estimation of pedestrians for the indoor localization system is as important as the estimation of the moving distance. Many conventional studies on heading direction estimation use a magnetometer to measure the magnetic north. However, the magnetometer reacts sensitively to the surrounding environment, such as walls, obstacles, and steel, resulting in errors that cannot correctly measure the magnetic north. Android smartphones provide the absolute heading direction through the rotation vector sensor by combining the data obtained from the accelerometer, magnetometer, and gyroscope. Further research is required to estimate a stable heading direction without using a magnetometer that is affected by the surrounding environment.

#### **3. Indoor Localization System**

In this section, we introduce a new indoor localization system for pedestrians that uses smartphones. Figure 3 illustrates the structure of the smartphone-based indoor position recognition system using the deep learning method proposed in this study. The proposed system consists of three steps: (1) classifying smartphone placements; (2) estimating the moving speed using deep learning, and (3) estimating the heading direction using game rotation vector sensors. The detailed operation of each step is described in the following subsection.

**Figure 3.** Indoor localization system overview.

#### *3.1. System Overview*

The first step was to classify the accelerometer and gyroscope data of pedestrians collected through smartphones as smartphone placements. There are many cases of smartphone placement; however, we assume only the four most representative cases. If it is possible to classify the collected data as smartphone placements, pedestrians can check the amount of data they collect in real-time. In addition, when sufficient pedestrian speed data, enough to achieve good performance, has been collected, the system stops collecting data to minimize battery consumption in smartphones.

The second step involved moving speed estimation using supervised learning. The 3- axis accelerometer data collected from the pedestrians' smartphones and the moving speed labels recorded every 1 s through GPS comprise the training datasets. Before constructing the training dataset, the accelerometer and GPS data were pre-processed. Since the 3-axis accelerometer data change as the smartphone's placement and tilt, regardless of these changes, acceleration data are collected with 3-axes fixed. In addition, accelerometer data are filtered through Kalman and low-pass filters. These filters minimize the impact of the drift of the accelerometer and sudden environmental changes. Because the labels of the deep learning model require high accuracy and reliability, only those GPS coordinates are used as labels and used to calculate the moving speed for which there are more than nine satellite signals that smartphones can receive. As explained in Section 2.2, most of the data were within the average walking speed. To eliminate this bias, additional data on various walking speeds were obtained using time-warping data augmentation technology. The training dataset obtained after these processes is used as an input to a deep learning model that estimates the moving speeds of pedestrians. To find the optimal deep learning model for estimating moving speed, we evaluated the accuracy of moving speed estimation by implementing seven supervised learning models.

In the third step, the heading direction of pedestrians is estimated. Magnetometers are extremely sensitive to the surrounding environment and may have errors, which will affect the estimation of the heading direction. Therefore, we estimated the heading direction using game rotation vector sensors that do not include magnetometers.

#### *3.2. Smartphone Placement Classification*

This section describes the technology used for classifying the collected data according to the placements in which pedestrians hold their smartphones. To classify the collected data according to each case, t-stochastic neighbor embedding (t-SNE) [25] unsupervised learning was used. t-SNE is a technique that classifies and visualizes high-dimensional vectors into 2- or 3-dimensional maps humans can understand, while preserving the distance between the data. The t-SNE unsupervised learning model uses accelerometer and gyroscope data as training datasets, and smartphone placements as labels (i.e., cases). Additional gyroscope values were used to increase the accuracy of the classification. Gyroscopes are suitable for data classification because the change in the value, which depends on the placement of the smartphone, is greater than that of the accelerometer. Although the accuracy should be evaluated according to all possible smartphone placements, this study assumes only four of the most commonly used. The four cases are as follows: (1) hand-held, (2) hand swing, (3) in pocket, (4) in a backpack. In this step, pedestrians can check the size of the collected data for each case in real time. In our empirical experiments, we found the proper data size to be 3 h per case (i.e., a total of 12 h) to ensure sufficient accuracy to estimate the moving speed. Thus, the data collection process stopped when the data size was at least 3 h and a total of 12 h to prevent excessive smartphone battery usage. This method allows pedestrians to know the minimum size of the training dataset for learning the deep learning model, thus gaining the practicality that battery consumption can be reduced in the data collection process.

#### *3.3. Moving Speed Estimation*

The moving speed estimation step consists of data pre-processing and a supervised learning-based deep learning model. The data needed to estimate the moving speed were the GPS and accelerometer values collected outdoors. Accelerometer data were used to extract the features of pedestrian gait patterns and were used as training datasets for the deep learning models. The moving speed calculated via GPS coordinates was used as a label for the training datasets as in [20].

The accelerometer data collected from the smartphones were pre-processed for use as input to the supervised learning model. The accelerometer data provided by the smartphone were device oriented. As can be seen in Figure 4, when the data are collected by device orientation, there is a problem in that the data show different characteristics depending on the placement and orientation of the smartphone from which they were collected. This means that even when moving in the same direction, the data values of the collected accelerometer vary depending on the tilt and placement of the smartphone.Because pedestrians can place the smartphone anywhere near the body, data should be collected with respect to three axes that are fixed regardless of the tilt and placement of the smartphone. To solve this problem, data pre-processing is used to convert the raw coordinates of the accelerometer (i.e., device-oriented coordinates) into earth-oriented coordinates. Alwin et al. [26] presented a method for converting device-oriented 3-axis accelerometer values into earth-oriented coordinates by multiplying them with rotation vector sensor values. The following Equation (1) represents a formula for transform the device-oriented coordinate to the earth-oriented coordinate.

**Figure 4.** Coordinate system (**a**) Device oriented coordinate (**b**) Earth oriented coordinate.

$$
\begin{bmatrix} A\_x \\ A\_y \\ A\_z \end{bmatrix} = \mathcal{R} \begin{bmatrix} a\_x & a\_y & a\_z \end{bmatrix}^T \tag{1}
$$

The *R* in the right term from Equation (1) represents the transform of the rotation vector value obtained through the rotation vector sensor into a rotation matrix, and *ax*, *ay* and *az* represents the raw value of accelerometer. Both values are obtained through smartphones. Each of *Ax*, *Ay* and *Az* in the left column represent the value of the three axes of acceleration converted to the earth reference coordinate system. Using this method, accelerometer values can be converted into earth-oriented coordinates to collect data, regardless of smartphone placement. The authors used Kalman filters and low-pass filters for the accelerometer data. Filtering accelerometer data eliminates drift and noise from smartphones.

In this paper, we use the pedestrian moving speed obtained through the GPS as a label for a deep learning model. Labels are correct answers to training data that are input to deep learning models, which affect the performance of deep learning models depending on the accuracy of the labels. In [20], the accuracy of the label is relatively low, because the moving speed was calculated and used as a label regardless of the reliability of GPS. Therefore, in this paper, to increase the reliability of labels on training datasets, we compose the training datasets with only the data collected when the receivable number of satellite

signals on smartphones is more than nine. This is a new and novelty method that has not been considered so far. The GPS error rate is inversely proportional to the number of satellite signals that a smartphone can receive, as shown in Figure 1. If the number of satellite signals that can be received is more than nine, high reliability of the label can be expected because the GPS measurement accuracy is approximately 98%. We calculated the moving speed for one second using the GPS coordinates when more than nine satellite signals were received, while collecting the sensor data. Equation (2) represents a formula for obtaining a moving speed of a pedestrian through a distance obtained by collecting GPS coordinates every second.

$$\text{Pedestrian Moving speed} = \text{distance} \div 1 \tag{2}$$

The calculated moving speed and accelerometer values were mapped for a period of one second and used as training data for the supervised learning model. This process can solve the reliability problem for labels collected in the GPS coordinates presented in Section 2.1.

As shown in Figure 2, most of the data collected at the average moving speed are concentrated at a particular moving speed. If the training data do not have sufficient data for all moving speed labels, the deep learning model will fail to estimate the exact moving speed if the pedestrian walks slower or faster than the average moving speed. Thus, to eliminate bias in the collected data, we introduced time-warping to augment the amount of data for various moving speeds. Time warping is a transformation that allows each element value in a sequence to be repeated by an arbitrary number and can compress or expands fixed-length time series data to a particular length. For example, two sequences *S* = {20, 20, 21, 20, 23} and *Q* = {20, 21, 21, 20, 20, 23, 23, 23} may be converted into the same sequence *A* = {20, 20, 21, 21, 20, 20, 23, 23, 23} by time warping. The distance between the two sequences after time warping is defined as a time warping distance. Figure 5 shows the results augmented to data of 24 h by time-warping the original data of 3 h. The black bar graph represents the original data, and the red bar graph represents the data enhanced through time-warping. By augmenting the data through time warping, the data can be constructed to have an even distribution at various moving speeds rather than being concentrated at a specific moving speed. This process solves the data-bias problem presented in Section 2.1.

The data of 12 h are augmented to a size of 96 h through time warping and are used as a training dataset for supervised learning-based deep learning models. The deep learning model derives a result by extracting patterns or features from the accelerometer data of the training dataset and estimating the moving speed for a one-second data segment when learning is completed. Estimation accuracy is the most important indicator of the performance of the deep learning model. One representative way to improve the accuracy of the model is to use an appropriate deep learning model. In this study, performance was evaluated by implementing seven deep learning models: CNN [27], GRU [28], LSTM [29], C-GRU, C-LSTM, GRU-C, and LSTM-C, to find the optimal deep learning model with the highest moving speed estimation accuracy. These models are explained below. A convolutional neural network (CNN) is a useful supervised learning model for identifying patterns to recognize images. CNNs are mainly used to find and learn patterns from training data and then classify new images using learned patterns. It is widely used in object recognition fields, such as self-driving cars and facial recognition. In contrast, the recurrent neural network (RNN), represented by long short-term memory (LSTM) and gated recurrent units (GRU), is a supervised learning model that has strengths in processing sequence data, such as time series and natural language. Because sequence data cannot understand the entire context simply by knowing and understanding only one data segment, LSTM and GRU are models that have improved existing RNNs to identify and learn the context of these sequence data. LSTM and GRU are used in various fields, such as voice recognition and sentence arrangement from listed words. Convolutional GRU (C-GRU) and convolutional LSTM (C-LSTM) refer to deep learning models in which CNN and RNN are combined and

are called convolutional recurrent neural networks (CRNNs). Given location and shape data, such as images, the correct answer is estimated by first extracting features from the CNN layer and inputting these features in chronological order into the RNN layer. That is, it is a model that extracts and utilizes time series data from image data. GRU convolutional (GRU-C) and LSTM convolutional (LSTM-C) extract features or patterns from data through convolutional layers and input them into the RNN layer in the same manner as CRNN, but the final output process is different. In the case of the CRNN, the correct answer is estimated by entering the output value of the RNN into several dense layers. However, in the case of LSTM-C and GRU-C, the output value of the RNN is input to one max pooling layer so that the output value of the layer appears as the final estimate. Figure 6 shows the model configuration diagram of the LSTM-C.

**Figure 5.** Original (black) and time-warped (red) moving speed data.

**Figure 6.** LSTM-C Model.

#### *3.4. Heading Direction Estimation*

In the heading direction estimation step, the exact heading direction of the pedestrians was measured. Android smartphones use a rotation vector sensor, including an accelerometer, gyroscope, and magnetometer, to measure the orientation of smartphones [30]. However, obstacles, walls, and steel can affect the magnetometer of the rotation vector sensor, so it can measure the wrong orientation. The other sensor for measuring the orientation is the game rotation vector sensor [31] provided by Android. It is identical to the rotation vector sensor in that it uses an accelerometer and a gyroscope, but it does not use a magnetometer. Hence, the game rotation vector sensor does not provide an absolute heading direction, that is, the magnetic north. Its *y*-axis represents the upward direction of the smartphone, not the north. Therefore, we used game rotation vector sensors instead of rotation vector sensors to measure the orientation. The game rotation vector is a combination of angles and axes in which the smartphone rotates by *ψ*, *θ*, and *φ* around the *x*-, *y*-, and *z*-axes, indicating the orientation of the device, as follows:

$$\mathbf{x}(\boldsymbol{\psi}) = \mathbf{x} \cdot \sin\left(\frac{\boldsymbol{\psi}}{2}\right) \tag{3}$$

$$y(\theta) = y \cdot \sin\left(\frac{\theta}{2}\right) \tag{4}$$

$$z(\phi) = z \cdot \sin\left(\frac{\phi}{2}\right) \tag{5}$$

The three-axis vector value obtained by the game rotation vector sensor is converted to a rotation matrix using quaternion through the getRotationMatricFromVector (getRMFV) function. Subsequently, the getOrientation function allows the rotation matrix acquired from the getRMFV function to be represented by the placement state of the smartphone. Three values are derived. The first value is the azimuth, the angle of rotation on the negative *z*-axis and represents the angle between the *y*-axis of the device and the Earth's Arctic point. The second value is the pitch, which is the angle of rotation on the *x*-axis, and represents the angle between the plane parallel to the screen of the smartphone and the plane parallel to the ground. The third value is the roll, that is, the angle of rotation on the *y*-axis, which represents the angle between the plane perpendicular to the ground and the plane perpendicular to the smartphone screen.

$$q1 = rotation\,Vector[0] \tag{6}$$

$$q2 = rotationVector[1] \tag{7}$$

$$q3 = \text{rotationVector}[2] \tag{8}$$

$$q0 = 1 - (q1\*q1) - (q2\*q2) - (q3\*q3) \tag{9}$$

The Rotation Vector [0], [1], and [2] are rotation vector values indicating the tilt of the smartphone same as Equations (3)–(5), respectively. Equations (6)–(9) represent quaternions used to transform the rotation vector value as a rotation matrix. The heading direction of pedestrians can be obtained from the azimuth, and the formula is as Equation (10). The *ψ*, *θ* and *φ* each represent an angle at which the smartphone is rotated with respect to the *x*-, *y*-, and *z*-axes, and the angle can be obtained by the rotation vector sensor.

$$\text{Azimuth} = \tan^{-1}((\cos\phi\sin\psi + \sin\phi\cos\theta\cos\psi) - (-\sin\phi\cos\psi - \cos\phi\cos\theta\sin\psi)) \tag{10}$$

Figure 7 shows a graph measuring the azimuth through a rotation vector sensor and a game rotation vector sensor by walking through a straight passage in a building. The black line represents the actual azimuth measured from the north using Google Maps. Because the rotation vector sensor includes a magnetometer, it is difficult to measure a stable azimuth owing to a door or an obstacle made of iron and even an empty space. However, the result

of measuring the azimuth angle using the game rotation vector sensor was very stable. Because the azimuth is measured using only accelerometers and gyroscopes, excluding the magnetometer, the results were very similar to the ground truth, except for the shaking caused by the walking of pedestrians.

**Figure 7.** Comparison of each azimuth through rotation vector sensor and game rotation vector sensor.

#### **4. Performance Evaluation**

#### *4.1. Evaluation Environments*

We evaluated the performance of the proposed system using a computer with the following specifications: Intel i5-6500 CPU, 40 GB RAM and Geforce RTX 2080 GPU. Datasets for supervised and unsupervised learning models were collected through the following processes: As shown in Figure 8, the training data were collected from the playground in Yongam Middle School in Sangdang-ku, Cheongju city, which was approximately 40 m × 90 m area, and had no obstacles or walls. We collected data for four situations. First, hand-held; second, hand-swing; third, in-pocket; and fourth, in a backpack. We collected training data over 10 h for each orientation, for a total of 40 h, as shown in Figure 9. The sampling rate of each sensor is 100 Hz, and the sensors used in this system are an accelerometer, gyroscope, GPS, and a game rotation vector sensor built into the Samsung Galaxy s10. Next, the conditions for collecting data for the validation data set were the same as the training data, except that it was collected inside the E10 building of Chungbuk National University. Table 1 presents the hyperparameters of seven deep learning models implemented to identify which model(s) are optimal for the indoor localization systems proposed in this paper.

(**a**)

**Figure 8.** Outdoor data collection environment.

**Figure 9.** 4 data collect situations (**a**) hand held (**b**) hand swing (**c**) in pocket (**d**) back pack.

**Table 1.** Deep learning model hyperparameters.

#### *4.2. Results of Smartphone Placement Classification*

Figure 10 shows the confusion matrix of the results from the t-SNE unsupervised learning model. The model was trained using a training data set of 40 h consisting of accelerometer and gyroscope data. The graph resulted from the validation data set of 2 h. The *x*-axis of the Figure 10 represents the results predicted by the unsupervised learning model, and the *y*-axis represents the case in which the actual data belong, that is, the label. For example, in the hand-held case, out of 7200 (half-hour data) samples, the model predicted 6875 data correctly as be hand-held (95.49%). For the remaining 325 data the model failed to classify them as hand held and classified into one of three other cases.

Figure 10 indicates that unsupervised learning using t-SNE can sufficiently classify the data collected in each case.

**Figure 10.** Smartphone placement classification result.

#### *4.3. Results of Moving Speed Estimation*

Table 2 shows the results of augmenting data of 12 h to 96 h with time-warping, using them to train seven models, and evaluating the accuracy of each model in estimating the moving speed with a validation data set of 2 h. Of the seven supervised learning models, the best performing model was the LSTM-C model, with approximately 95.6% accurate moving speed estimation. Therefore, the deep learning model to be used in the indoor localization systems proposed in this study was determined to be LSTM-C.

Figure 11 shows the confusion matrix graph of the movement speed estimation of the LSTM-C model. The LSTM-C model was trained using a non-augmented training data set of 40 h. As shown in the Figure 11, the LSTM-C model estimated the data for 1.4 m/s with a high accuracy of 97.6%. However, data belonging to labels other than 1.4 m/s showed relatively low accuracy. These results show that most of the training dataset is densely distributed around 1.4 m/s, as shown in Figure 2, and that the model has not learned enough features for other moving speed labels to classify them correctly. Accordingly, in this study, the training dataset was augmented with time warping to obtain an even distribution across various moving speed labels.

**Figure 11.** Moving speed estimation using LSTM-C.

Table 3 shows the results of the estimation accuracy of the LSTM-C model, trained by the various training datasets augmented with time warping for moving speed. The TW class represents the number of classes in which the original data is augmented using timewarping. For example, if the TW class is one, the training data are not augmented, if the TW class is three, the training dataset is augmented to three classes, including the original data. With the original data without augmentation, sufficient moving speed estimation accuracy was not achieved. When the TW class was 3, sufficient accuracy in estimating the moving speed for the original data of 16 h and 20 h was observed. However, by checking the loss graph, we found an overfitting problem and did not see high accuracy for various moving-speed labels. Using a confusion matrix, as shown in Figure 11, it was found that the accuracy of the approximately 1.5 m/s label was sufficiently high, but similar accuracy could not be achieved for the other moving speed labels. When the TW class was 5 or 7, sufficient accuracy was achieved, and overfitting problems did not occur. However, the data were not augmented for various moving speed labels; therefore, the model did not show a high accuracy for all labels, as shown in Figure 11.

**Table 3.** Moving speed estimation accuracy of LSTM-C model according to data size.

However, when the TW class was more than nine, including the original data, the model showed high accuracy for all labels. If the original data are augmented to more than nine TW classes, the indoor localization system proposed in this study can obtain a high moving speed estimation accuracy for all moving speed classes. However, the larger the total size of the training data set, created by increasing the number of TW classes, the smaller is the increase in accuracy, and the amount of data increases rapidly. For example, the data augmented with 5 and 13 TW classes from 12 h of original data were 60- and

156 hours, respectively, but achieved 95% and 96% accuracy, respectively. In this case, the amount of data increased significantly; however, the accuracy increased only by less than 1%. Of course, it is better to augment and learn the original data into 13 TW classes from the perspective of performance, but this is not practical from a system user perspective. The indoor localization system proposed in this paper categorizes the collected data using unsupervised learning, augments the training dataset with time warping and then learns through the LSTM-C model. These processes require a great deal of time, especially the process of augmenting with time-warping and performing learning of augmented data with deep learning models; the larger the dataset, the more time it takes. Therefore, in this study, the minimum size of the original data required for learning the deep learning model parameters was limited to 3 h for each case, i.e., a total of 12 h, and the number of TW classes was set to nine, including the original data.

Figure 12 shows a CDF graph of the moving speed estimation error rate of an LSTM-C model that learns the training data set augmented to 96 h and applies the improvements proposed in this paper for three different comparators. The red line is a CDF graph of the error rate for estimating the moving speed of the original data of 12 h without augmentation. A marked improvement in accuracy, compared to the other lines, can be seen for the black line, which is the result of applying all the improvements proposed in this study. Furthermore, as shown in Figure 5, time warping eliminates data bias, which increases the estimation accuracy performance for various moving speeds. The blue line is a CDF graph of the moving speed estimation error rate for the test data of 2 h after learning the LSTM-C model by augmenting the collected data of 12 h into nine TW classes, regardless of the number of satellites, to evaluate the reliability of the ground truth information. If data are collected regardless of the number of satellites, the blue line in Figure 12 shows that the exact moving speed cannot be calculated accurately because of the lack of reliability in the moving speed labels, that is, the ground-truth information required for the supervised learning model is not reliable. However, the data collected when the number of satellites is greater than nine are relatively high in accuracy for the moving speed label and show a higher performance. This means that the higher the reliability of the previously mentioned ground-truth information, the better are the deep learning model results. The green line is a CDF graph of the performance of the training dataset collected using device-oriented coordinates. If the data are collected by the device-oriented coordinate system, the sensor value depends on the *y*-axis of the smartphone. However, when data are collected through an earth-oriented coordinate system, the sensor value does not change depending on smartphone placement. For example, when a smartphone is freely placed at a moving speed of 1.5 m/s for 10 s, the data collected into a device-oriented coordinate system shows significant variations depending on the placement of the smartphone. That is, the 3-axis accelerometer sensor varies with each change in the smartphone placement, but for the earth-oriented coordinate, the values of the 3-axis of the collected accelerometer values do not change even if the smartphone placement changes. It can be seen from the green line in Figure 12 that the device-oriented coordinate data show a large error compared to the data collected through the earth-oriented coordinate. This means that the process of generalizing training data has a significant impact the deep learning model outcome and that the indoor localization system proposed in this paper, which transforms the sensor data collected into earth-oriented coordinates and performs the generalization process and produces improved results.

**Figure 12.** CDF graph of moving speed estimation.

#### *4.4. Results of Indoor Localization System*

This section evaluates the performance of path estimation of indoor localization systems by collecting test datasets for routes, including straight paths and rotations in indoor environments. Table 4 lists different versions of the training datasets for evaluating the performance of indoor localization systems. For example, the 'Without augmentation' training dataset refers to a dataset that is composed of data transformed the device-oriented coordinate to the earth-oriented coordinate when the receivable number of satellite signals is more than nine but is not augmented by time-warping. Another example is the 'Unfiltered GPS' training dataset, which is composed of data that transformed the device-oriented coordinate to the earth-oriented coordinate and is augmented by time-warping but is composed in all situations, regardless of the receivable number of satellite signals. Finally, the 'Device oriented coordinate' training dataset that is composed of data collected when the receivable number of satellite signals is more than nine and augmented by time-warping but does not transform the device-oriented coordinate to the earth-oriented coordinate. On the other hand, the 'Proposed' training dataset refers to a dataset with all the techniques proposed in this paper.

**Table 4.** Parameters for each training dataset.

Figure 13 shows the results of the path estimation of the test dataset collected inside a horseshoe-shaped building. The black double line path represents the ground truth information, and the black path with crosses (proposed) is the result of the path estimation of the indoor localization system proposed in this paper. We collected the data, while walking through the black double line, as shown in Figure 13, and the author's smartphone, the Samsung Galaxy s10, was used as the data collection device. In the process of collecting this data, we collected the data, while walking along a path of a total length of 240 m and conducted a total of five-time experiments. In the process of collecting this data, we collected the data, while walking along a path of a total length of 240 m and conducted a total of five time experiments. First, the estimation results of the proposed indoor location recognition system showed a positioning error rate of approximately 3 to 5 m compared to

the ground truth. This is a very low error rate compared to other comparators. The blue path (unfiltered GPS) is the result of estimating the path by learning the supervised model with the data collected, regardless of the number of GPS satellites. Regardless of the number of GPS satellites, it is difficult to achieve consistency and high reliability for the collected GPS coordinates. The GPS coordinates collected even when walking at the same speed and path depend on the surrounding environment and the number of satellite signals currently available to the smartphone. The blue path in Figure 13 shows that the errors resulting from the ground truth information significantly influence the overall performance of the system. The red path (without augmentation) is the result of estimating the path by learning 40 h of data without the use of time warping into a supervised learning model. Assuming that the experiment site was a straight path, the distance between the start and end points would not be significantly different from the ground truth. However, after the first right rotation, the red route shows a very large error compared with the ground truth. This is because the deep learning model, which learned training datasets without data augmentation, did not achieve sufficient moving-speed estimation accuracy for various moving-speed labels. Thus, the red route showed unexpected results from accumulated moving speed estimation errors. The green path (device-oriented coordinates) is the result of estimating the path by learning a training dataset that has not converted the device-oriented coordinates into earth-oriented coordinates using a supervised learning model. The data collected with device-oriented coordinates had different characteristics depending on the placement of the smartphone during data collection. As mentioned in Section 2, data that have not been generalized are difficult to use as training datasets for supervised learning models because the 3-axis of the accelerometer varies depending on the tilt or placement of the smartphone. Table 5 represents the positioning error with meters for each supervised learning model that was trained by four different training datasets from a total of five time experiments.

**Figure 13.** Indoor localization result.

**Table 5.** Positioning error for each method at every epoch.

## *4.5. Scenario*

The smartphone-based indoor localization system using deep learning proposed in this study aims for more practical use by pedestrians by providing on-demand services. Pedestrians can construct a personal indoor localization system exclusively for themselves simply by walking outdoors, while using a smartphone. The virtual scenarios for constructing pedestrian-individual systems are as follows.

Accelerometers, gyroscopes, and GPS data were collected because GPS signals can be received when pedestrians go outdoors. Afterward, when pedestrians enter the indoor environment from the outside and cannot receive GPS signals, data collection is temporarily stopped, but the data collected till then are stored in their smartphones. At this time, we assume that the collected data are valid only when there are nine or more satellite signals that can be received by smartphones, and we exclude the data when there are fewer than nine. Then, the accelerometer and gyroscope data are input into the t-SNE unsupervised learning model to classify the collected data into four cases. The size of the classified data is measured to determine whether the data size reached 3 h for each case. When training data of 3 h or a total of 12 h are accumulated for each case, smartphones stop collecting data outdoors permanently, reducing excessive battery consumption. After the training dataset of 12 h is augmented to a total size of 96 h through time warping, this training dataset is used to learn the LSTM-C model that estimates the pedestrian moving speed. When the learning is completed, pedestrians can check their path in real time by estimating the moving speed and heading direction using only accelerometer data and indoor game rotation vector sensors.


**Marine Anti-Inflammatory and Antioxidant Agents 2.0**

Editors

**Donatella Degl'Innocenti Marzia Vasarri**

MDPI • Basel • Beijing • Wuhan • Barcelona • Belgrade • Manchester • Tokyo • Cluj • Tianjin

*Editors* Donatella Degl'Innocenti Universita degli Studi di ` Firenze Italy

Marzia Vasarri Universita degli Studi di ` Firenze Italy

*Editorial Office* MDPI St. Alban-Anlage 66 4052 Basel, Switzerland

This is a reprint of articles from the Special Issue published online in the open access journal *Marine Drugs* (ISSN 1660-3397) (available at: https://www.mdpi.com/journal/marinedrugs/ special issues/Anti inflammatoryAntioxidantAgents2).

For citation purposes, cite each article independently as indicated on the article page online and as indicated below:

LastName, A.A.; LastName, B.B.; LastName, C.C. Article Title. *Journal Name* **Year**, *Volume Number*, Page Range.

**ISBN 978-3-0365-6784-6 (Hbk) ISBN 978-3-0365-6785-3 (PDF)**

© 2023 by the authors. Articles in this book are Open Access and distributed under the Creative Commons Attribution (CC BY) license, which allows users to download, copy and build upon published articles, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications.

The book as a whole is distributed by MDPI under the terms and conditions of the Creative Commons license CC BY-NC-ND.


**Meet the editor**

Dr. Aimé Peláiz Barranco is a full professor in the Physics Faculty, Havana University, Cuba. Her activities range from teaching to advising undergraduate and graduate students and doing high-quality research. She is one of the leaders in the development of ferroelectric and antiferroelectric materials researches in Cuba and the international coordinator of the Latin American

Network of Ferroelectrics Materials. She has authored 100 scientific papers in refereed journals and presented an important number of research works at scientific congresses. Her results have been recognized in Cuba and worldwide through the award of several prizes, such as TWOWS Award for Young Women Scientists (2010), TWAS-ROLAC Award for Young Scientists (2011), and CAS-TWAS Award for Young Scientists (2012).


Structure, Dynamics and Colloidal Stability

*Colloids - Types, Preparation and Applications*

Deterg 2014;51:379-86. https://doi.

[44] Wang X, Yang H, Wang F. A cationic gemini-surfactant as effective inhibitor for mild steel in HCl solutions. Corros Sci 2010;52:1268-76. https://doi. org/10.1016/j.corsci.2009.12.018.

[45] FU Wei LL -s. -b. -f. Synthesis of gemini quaternary ammonium salt surfactants and their application performance on fabric. China Surfactant

[46] Li W, Sun C, Hou B, Zhou X. Room Temperature Synthesis and Catalytic Properties of Surfactant-Modified Ag Nanoparticles 2012;2012. https://doi.

org/10.3139/113.110319.

Deterg Cosmet 2009.

org/10.1155/2012/638692.

**80**

**83**

**Chapter 5**

**Abstract**

*Ranganatha Sudhakar*

supercapacitors are discussed.

carbon materials

**1. Introduction**

Aerogels Utilization in

Electrochemical Capacitors

**Keywords:** supercapacitors, porous, mesoporous, specific capacitance,

energy conversion and storage including solar cells [1, 2].

Rapid growth of human society and subsequent need of energy is driving the manipulation of non-renewable sources in nature leading to depletion of the same. This is simultaneous with the increasing threats such as global warming, energy shortage, air pollution etc. Standardization of our life style and drastic change in dependence on electricity, demanding urgent need for high efficiency energy conversion and storage. Batteries and supercapacitors are excellent means of electrical

Conventional condensers or capacitors utilize dielectric materials, e.g., ceramics, polymers which are non-conducting in nature, exhibit the capacitance in the range of pico to microfarad. Typically, anodic metal oxides mostly of Ta, Al, Nb are used in electrochemical capacitors which widen the capacity from micro to millifarad level. Recently, supercapacitors are devised involving energy mechanisms; electric double-layer capacitance (EDLC) and pseudocapacitance. Charge separation at electrode/electrolyte interface results in EDLC and fast, reversible reactions occurring on solid electrode surface leads generation of pseudocapacitance. RuO2 and IrO2 noble metals exhibit superior specific capacitance value of about 750 F/g but at the same time hazardous and non-economical. For this reason, oxides of transition

Supercapacitors are the integral part of electrochemical energy conversion and storage media. Energy storage mechanism is different in supercapacitors compared to batteries and results in exhibition of excellent power density. The supercapacitor performance is sensitive to material used as electrode, nature of electrolyte, etc. and the very significant is electrode surface nature. Based on the type of energy storage mechanism, supercapacitors are divided as electrochemical double-layer capacitors and pseudocapacitors. There is a practice to have both kind of these materials as electrode materials to achieve high electrochemical performance. Aerogels with inherent characteristics such as large pores, very high surface area, and superior mechanical stability make them superior candidates for electrode materials for high performance electrochemical supercapacitors. In this chapter, aerogels derived from different sources, their suitability and performance in view of electrochemical


**17. Histological characteristics of stromal endometriosis**

The presence of stromal elements in the absence of glandular epithelium in foci of endometriosis constitutes the stromal endometriosis. This is encountered in the ovary, in the cervix and the peritoneum and usually is associated with a focus of typical endometriosis.


*3.1.2 Biochar as soil conditioner*

From the agricultural point of view, the application of carbonization products for soil amelioration seems to be beneficial because the treatment improves the conditions for plant growth, leading to a better yield [21]. Furthermore, due to the rapid effects and relatively low costs of such treatment, biochars are more

and more frequently used in processes of soil remediation and conservation. Moreover, the application of biochars to soil leads to increased contents not only of carbon but also of other biogenic compounds, such as phosphorus, potassium, magnesium and nitrogen [7, 22]. By increasing NH3 and NH4 + retention, reducing N2O emissions and eluting NO3 ions, as well as inducing the development of nitrogen bacteria which directly affects the increase in soil productivity, biochar helps to store nitrogen. Biochar also impacts the physical properties of soil by improving its water retention, capacity to form aggregates, and resistance to erosion. Owing to their highly porous structure, carbonization products may create favorable conditions for microorganisms, as a consequence improving the fertility and productivity of soils.


**3.2.4** *ERCC1* **Asn118Asn**

The results from studies by Skjelbred *et al*. (Skjelbred et al., 2006a) , Joshi *et al*. (Joshi et al., 2009) , and our Danish study (Hansen et al., 2008) on the *ERCC1* Asn118Asn polymorphism suggest no association with risk of colorectal cancer.

Moreno *et al*. examined five polymorphisms in the *ERCC1* gene. A haplotype containing the minor allele of three of the *ERCC1* polymorphisms was associated with a higher risk of colorectal cancer (OR=2.3, 95% CI: 1.0-5.3) compared with carriers of the most frequent haplotype (Moreno et al., 2006). Two other SNPs in the *ERCC1* gene were not associated with risk of colorectal cancer (Mort et al., 2003; Berndt et al., 2006).

#### **3.3 SNPs in NER and risk of other types of cancer than colorectal cancer**

Numerous association studies of polymorphisms in genes involved in NER are reported on various types of cancer, with the majority of studies focused on the *XPD* Lys751Gln and *XPD* Asp312Asn polymorphisms. A meta-analysis of lung cancer by Kiyohara *et al.* (with 1913 cases and 1882 controls of different ethnicities) (Kiyohara & Yoshimasu, 2007) suggested among other studies (Xing et al., 2002; Hu et al., 2004; Yin et al., 2006), that carriers of the variant alleles of either of the two *XPD* polymorphisms were found to be at higher risk of lung cancer, while a number of other studies did not observe any association of the two polymorphisms with lung cancer risk (De et al., 2007; Vogel et al., 2005b; Popanda et al., 2004; Hu et al., 2006).

Polymorphisms in Nucleotide Excision Repair

Genes and Risk of Colorectal Cancer: A Systematic Review 549

Table 2. Studies of possible associations between polymorphisms in *XPD*, *XPA*, *XPC,* and *ERCC1* and risk of colorectal adenomas or colorectal cancer and gene-environment (G E) interaction on risk of colorectal adenomas or colorectal cancer. The results reviewed and included are solely on polymorphisms in the four genes and the environmental factors that are the topic of the present book chapter.

Table 2. Studies of possible associations between polymorphisms in *XPD*, *XPA*, *XPC,* and *ERCC1* and risk of colorectal adenomas or colorectal cancer and gene-environment (G E) interaction on risk of colorectal adenomas or colorectal cancer. The results reviewed and included are solely on polymorphisms in the four genes and the environmental factors that are the topic of the present book chapter.

548 DNA Repair

Polymorphisms in Nucleotide Excision Repair

al., 2006).

results are inconsistent.

satisfactorily clarified at present.

**4. Discussion**

Genes and Risk of Colorectal Cancer: A Systematic Review 551

Hu et al., 2006): Individuals with both putative genotypes of *XPC* Lys939Gln and *XPC* Ala499Val polymorphisms are observed with a 2.4-fold (OR=2.37, CI: 1.33-4.21) higher risk of lung cancer compared with individuals with both wild type genotypes (Vogel et al., 2005b; Lee et al., 2005; Hu et al., 2006), with the higest risk observed among smokers.  A lower risk of endometrial cancer may be associated with carriage of at least one variant allele for both

In a Korean population carriers of the wild type allele (G/G or A/G) in the *XPA* G23A polymorphism were reported to have a lower risk of lung cancer compared to carriers of the A/A genotype, with an OR of 0.56 (CI:0.35-0.90) (Park et al., 2002). Similar results were obtained in studies on lung cancer risk in Caucasians and Mexican-Americans (Vogel et al., 2005b; Wu et al., 2003) (Popanda et al., 2004), while a Norwegian study observed the inverse effect with a 1.6-fold higher risk (OR=1.59, CI:1.12-2.27) of lung cancer among carriers of the G/G genotype compared with carriers of the A-allele (Zienolddiny et al., 2006). When stratifying by smoking status the protective effect for lung cancer was only observed among ever smokers (Wu et al., 2003) or current smokers (Park et al., 2002) carrying at least one Gallele or the G/G genotype, respectively. A tendency for lower risk of basal cell carcinoma has been observed among carriers of the variant G-allele, with an OR of 0.82 (CI: 0.66-1.01) and an OR of 0.74 (CI: 0.53-1.03) for homozygous and heterozygous carriers, respectively (Miller et al., 2006). The same tendency was observed for risk of squamous cell carcinoma (Miller et al., 2006). Carriage of at least one A-allele for *XPA* G23A was associated with decreased risk of endometrial cancer, OR=0.47 (CI:0.25-0.82) compared with carriers of the G/G genotype, but only among women with a history of using oral contraceptives (Weiss et

The *ERCC1* Asn118Asn polymorphism is not associated with testicular cancer (Laska et al., 2005). Furthermore, no association has been observed for the *ERCC1* Asn118Asn polymorphism to risk of endometrial cancer (Jo et al., 2007; Weiss et al., 2006), ovarian

All in all the studies suggest that the two *XPD* polymorphisms at amino acid position 312 or 751, the *XPD* Lys751Gln in particular, are associated with risk of cancer in the lung, breast and bladder and seems to modify the effect of smoking on risk of the three cancer forms. The *XPC* Lys939Gln polymorphism may possibly be associated with risk of bladder cancer, and the *XPA* G23A polymorphism may be associated with risk of skin cancer (basal cell carcinoma), endometrial cancer and lung cancer. However, the studies are few and the

In summary, this review, limited by the bias against publication of null findings, highlights the complexities inherent in epidemiological research and, particularly, in molecular epidemiological research on colorectal cancer. Studies on possible associations between SNPs in genes involved in defence of oxidative DNA damages and in nucleotide excision repair and risk of colorectal cancer have not obtained consistent results, why the issue of whether the SNPs are possible biomarkers of susceptibility for colorectal cancer is not

cancer (Jo et al., 2007) and adult glioma (Wrensch et al., 2005).

*XPC* Lys939Gln and *XPC* Ala499Val polymorphisms (Weiss et al., 2005).

Two large meta-analyses (with 3725 cases and 4152 controls) included identical nine casecontrol studies but made two dissimilar conclusions: The *XPD* Lys751Gln and *XPD* Asp312Asn polymorphisms are associated with risk of lung cancer (Hu et al., 2004) or no clear association was found (Benhamou & Sarasin, 2005). Some studies suggest an interaction between the two *XPD* polymorphisms and smoking in relation to risk of lung cancer (De et al., 2007; Hu et al., 2006; Xing et al., 2002).

Combinations of the *XPD*, *XPC* and *XPA* genotypes, variant alleles, is suggested to be associated with higher risk of lung cancer (Vogel et al., 2005b). This may be plausible but in the light of multiple testing and the low number of cases this may be a chance finding. The largest breast cancer studies by the number of individuals, 1053 cases/1102 controls (Terry et al., 2004) and 1830 cases/1262 controls (Debniak et al., 2006) observed modest associations of the *XPD* polymorphisms with breast cancer risk. Carriers of the variant *XPD* Lys751Gln allele was associated with a 20% higher risk (OR=1.21, CI: 1.01-1.44) compared with homozygous carriers of the wild type allele. The risk seemed limited to those with a PAH-DNA adduct level above the median, with an OR of 1.61 (CI: 0.99-2.63) among homozygous carriers of the *XPD* 751Gln allele (Terry et al., 2004).  However, higher risk has been detected among ever smoking women carrying the *XPD* 751Gln allele (OR=2.52, CI: 1.27-5.03) compared to ever smoking women carrying the homozygous wild type allele (Metsola et al., 2005). Association with breast cancer risk has been detected when the homozygous variant *XPD* Lys751Gln allele and the homozygous variant *XPD* Asp312Asn allele segregated together, with OR=1.5 (p<0.05) and OR=3.69 (CI: 1.76-7.74), respectively (Debniak et al., 2006; Justenhoven et al., 2004). A large study including 2485 cases with single primary melanoma and 1238 cases with second or higher order primary melanomas detected higher melanoma risk among homozygous carriers of the variant *XPD* Lys751Gln allele (OR=1.4, CI: 1.1-1.7) or the variant *XPD* Asp312Asn allele (OR=1.5, CI: 1.2-1.9), respectively (Millikan et al., 2006). Similar results were obtained in a study by Li *et al*. (Li et al., 2006b), while another study observed the inverse association for both polymorphisms (Han et al., 2005). When stratifying by age Baccarelli *et al.* observed an association of the two *XPD* polymorphisms to risk of melanoma only among the individuals older than 50 years when diagnosed (Baccarelli et al., 2004). The *XPD* Lys751Gln (Andrew et al., 2006) and the *XPD* Asp312Asn polymorphism (Wu et al., 2006) have been associated with risk of bladder cancer. An interaction is suggested between the *XPD* Lys751Gln polymorphism and smoking in relation to bladder cancer risk (Andrew et al., 2006; Stern et al., 2002; Schabath et al., 2005). Individuals carrying both the variant *XPD* alleles were more susceptible to development of bladder cancer (Wu et al., 2006; Andrew et al., 2006) than carriers of wild type alleles.

A small study suggest that the variant allele of the polymorphism XPC Lys939Gln is associated with higher risk of bladder cancer (OR=1.49, CI:1.16-1.92) (Sanyal et al., 2004). No association is observed between the polymorphism and risk of lung cancer (Vogel et al., 2005b; Lee et al., 2005; Hu et al., 2006) but a haplotype encompassing more polymorphisms in *XPC* may contribute to a higher risk of lung cancer (Vogel et al., 2005b; Lee et al., 2005;

Two large meta-analyses (with 3725 cases and 4152 controls) included identical nine casecontrol studies but made two dissimilar conclusions: The *XPD* Lys751Gln and *XPD* Asp312Asn polymorphisms are associated with risk of lung cancer (Hu et al., 2004) or no clear association was found (Benhamou & Sarasin, 2005). Some studies suggest an interaction between the two *XPD* polymorphisms and smoking in relation to risk of lung

Combinations of the *XPD*, *XPC* and *XPA* genotypes, variant alleles, is suggested to be associated with higher risk of lung cancer (Vogel et al., 2005b). This may be plausible but in the light of multiple testing and the low number of cases this may be a chance finding. The largest breast cancer studies by the number of individuals, 1053 cases/1102 controls (Terry et al., 2004) and 1830 cases/1262 controls (Debniak et al., 2006) observed modest associations of the *XPD* polymorphisms with breast cancer risk. Carriers of the variant *XPD* Lys751Gln allele was associated with a 20% higher risk (OR=1.21, CI: 1.01-1.44) compared with homozygous carriers of the wild type allele. The risk seemed limited to those with a PAH-DNA adduct level above the median, with an OR of 1.61 (CI: 0.99-2.63) among homozygous carriers of the *XPD* 751Gln allele (Terry et al., 2004).  However, higher risk has been detected among ever smoking women carrying the *XPD* 751Gln allele (OR=2.52, CI: 1.27-5.03) compared to ever smoking women carrying the homozygous wild type allele (Metsola et al., 2005). Association with breast cancer risk has been detected when the homozygous variant *XPD* Lys751Gln allele and the homozygous variant *XPD* Asp312Asn allele segregated together, with OR=1.5 (p<0.05) and OR=3.69 (CI: 1.76-7.74), respectively (Debniak et al., 2006; Justenhoven et al., 2004). A large study including 2485 cases with single primary melanoma and 1238 cases with second or higher order primary melanomas detected higher melanoma risk among homozygous carriers of the variant *XPD* Lys751Gln allele (OR=1.4, CI: 1.1-1.7) or the variant *XPD* Asp312Asn allele (OR=1.5, CI: 1.2-1.9), respectively (Millikan et al., 2006). Similar results were obtained in a study by Li *et al*. (Li et al., 2006b), while another study observed the inverse association for both polymorphisms (Han et al., 2005). When stratifying by age Baccarelli *et al.* observed an association of the two *XPD* polymorphisms to risk of melanoma only among the individuals older than 50 years when diagnosed (Baccarelli et al., 2004). The *XPD* Lys751Gln (Andrew et al., 2006) and the *XPD* Asp312Asn polymorphism (Wu et al., 2006) have been associated with risk of bladder cancer. An interaction is suggested between the *XPD* Lys751Gln polymorphism and smoking in relation to bladder cancer risk (Andrew et al., 2006; Stern et al., 2002; Schabath et al., 2005). Individuals carrying both the variant *XPD* alleles were more susceptible to development of bladder cancer (Wu et al., 2006; Andrew et al., 2006) than carriers of wild type alleles.

(Ritchey et al., 2005) or gastric cancer (Huang et al., 2005).

A small study suggest that the variant allele of the polymorphism XPC Lys939Gln is associated with higher risk of bladder cancer (OR=1.49, CI:1.16-1.92) (Sanyal et al., 2004). No association is observed between the polymorphism and risk of lung cancer (Vogel et al., 2005b; Lee et al., 2005; Hu et al., 2006) but a haplotype encompassing more polymorphisms in *XPC* may contribute to a higher risk of lung cancer (Vogel et al., 2005b; Lee et al., 2005; Hu et al., 2006): Individuals with both putative genotypes of *XPC* Lys939Gln and *XPC* Ala499Val polymorphisms are observed with a 2.4-fold (OR=2.37, CI: 1.33-4.21) higher risk of lung cancer compared with individuals with both wild type genotypes (Vogel et al., 2005b; Lee et al., 2005; Hu et al., 2006), with the higest risk observed among smokers.  A lower risk of endometrial cancer may be associated with carriage of at least one variant allele for both *XPC* Lys939Gln and *XPC* Ala499Val polymorphisms (Weiss et al., 2005).

In a Korean population carriers of the wild type allele (G/G or A/G) in the *XPA* G23A polymorphism were reported to have a lower risk of lung cancer compared to carriers of the A/A genotype, with an OR of 0.56 (CI:0.35-0.90) (Park et al., 2002). Similar results were obtained in studies on lung cancer risk in Caucasians and Mexican-Americans (Vogel et al., 2005b; Wu et al., 2003) (Popanda et al., 2004), while a Norwegian study observed the inverse effect with a 1.6-fold higher risk (OR=1.59, CI:1.12-2.27) of lung cancer among carriers of the G/G genotype compared with carriers of the A-allele (Zienolddiny et al., 2006). When stratifying by smoking status the protective effect for lung cancer was only observed among ever smokers (Wu et al., 2003) or current smokers (Park et al., 2002) carrying at least one Gallele or the G/G genotype, respectively. A tendency for lower risk of basal cell carcinoma has been observed among carriers of the variant G-allele, with an OR of 0.82 (CI: 0.66-1.01) and an OR of 0.74 (CI: 0.53-1.03) for homozygous and heterozygous carriers, respectively (Miller et al., 2006). The same tendency was observed for risk of squamous cell carcinoma (Miller et al., 2006). Carriage of at least one A-allele for *XPA* G23A was associated with decreased risk of endometrial cancer, OR=0.47 (CI:0.25-0.82) compared with carriers of the G/G genotype, but only among women with a history of using oral contraceptives (Weiss et al., 2006).

The *ERCC1* Asn118Asn polymorphism is not associated with testicular cancer (Laska et al., 2005). Furthermore, no association has been observed for the *ERCC1* Asn118Asn polymorphism to risk of endometrial cancer (Jo et al., 2007; Weiss et al., 2006), ovarian cancer (Jo et al., 2007) and adult glioma (Wrensch et al., 2005).

All in all the studies suggest that the two *XPD* polymorphisms at amino acid position 312 or 751, the *XPD* Lys751Gln in particular, are associated with risk of cancer in the lung, breast and bladder and seems to modify the effect of smoking on risk of the three cancer forms. The *XPC* Lys939Gln polymorphism may possibly be associated with risk of bladder cancer, and the *XPA* G23A polymorphism may be associated with risk of skin cancer (basal cell carcinoma), endometrial cancer and lung cancer. However, the studies are few and the results are inconsistent.


**5.1 Gestational diabetes mellitus (GDM)**

GDM is transient glucose intolerance first detected during pregnancy. Manifestation usually occurs in the second and third trimesters. After delivery, the impaired glucose metabolism is corrected, and the glucose level moves within the normal range.

At the beginning of pregnancy, the main goal of the mother's metabolism is to build up sufficient reserves of energy to be used for foetal growth [121]. With the end of the first trimester, insulin resistance of muscle and adipose tissue gradually begins to develop, reaching its peak during the third trimester. The volume of adipose tissue decreases and the supply of free fatty acids increases, which newly become the main source of energy for the maternal organism. Glucose is redirected by the placenta to the foetus. Despite significant insulin resistance development of diabetes in pregnancy usually does not occur.

The HAPO study in 2008 demonstrated a strong association between glycaemia values and the perinatal complications which was almost linear and already evident at the level of glycaemia, which until then was considered completely physiological [122]. This study led to the development of a new guideline for screening and diagnosis of gestational diabetes [123]. Our centre, like others in the Czech Republic, adopted these criteria in 2015 (**Table 4**).

The primary treatment of GDM consists of dietary control, adequate physical activity and weight management remain the cornerstones of GDM treatment.

*FPG=fasting plasma glucose; PG=plasma glucose; 75g oGTT=oral glucose tolerance test with 75g of glucose. 1 At least 2 measurements on separate days.*

## **Table 4.**

*Diagnostic criteria for GDM (adopted from IADPSG).*


3. An introduction to decision-making

Traditionally, a decision is defined as being a choice: a choice about a course of action [16], the choice of a strategy for action [17], a choice leading to a certain desired objective [18]. It can be clearly understood that decision-making as a non-random activity concluding in the selection of one course of action among multiple strategies and DSS is a prevailing system that can ease this process [6].

Simon stated that the process of making the decision includes three basic phases: intelligence, design, and choice [19]. Turban described how implementation, is also required over and above a "paper" solution, as the fourth phase, in order to solve the original problem [2].

The intelligence phase, or problem identification, involves gaining awareness that inconsistencies exist between the current state of a situation and the desired circumstances. At this level the decision maker tries to diagnose the problems that need to be addressed and/or opportunities that need to be tracked [20].

In the design phase, a decision maker attempts to generate alternatives, and analyses the options to provide knowledge about their relevant implications. During this phase, the decision maker may find that supplementary knowledge is required. This leads to a return to the intelligence stage to clarify the problems before continuing with the design activity [6].

During the choice phase, the decision maker selects one of the proposed alternatives that have been explored in the design phase. The outcome depends on the nature of the decision context and the decision maker's own traits and idiosyncrasies. It may be that none of the alternatives are satisfying (return to the design phase), that several competing alternatives gain high scores, or that the state of the context has changed dramatically after analysis of alternatives (return to the intelligence phase). However, one option must be chosen for implementation [21].

The fourth and final step is implementation. This phase includes a set of chosen solutions that need to be approved by stakeholders and put into action over time [20]. This requires cautious planning and sensitivity to those involved in the process and/or those affected by it. The resolution must then be monitored to guarantee that the problem has been corrected. If the problem has been rectified, then the decision-making procedure is finalized [22]. Generally, the outcome of successful implementation is solving the real problem while any failure results in returning to a former phase of the process [2].

### 3.1. The structure of decisions

3. An introduction to decision-making

Figure 3. The desirable characteristics and capabilities of DSS.

opportunities that need to be tracked [20].

this process [6].

24 Management of Information Systems

Traditionally, a decision is defined as being a choice: a choice about a course of action [16], the choice of a strategy for action [17], a choice leading to a certain desired objective [18]. It can be clearly understood that decision-making as a non-random activity concluding in the selection of one course of action among multiple strategies and DSS is a prevailing system that can ease

Simon stated that the process of making the decision includes three basic phases: intelligence, design, and choice [19]. Turban described how implementation, is also required over and above a "paper" solution, as the fourth phase, in order to solve the original problem [2].

The intelligence phase, or problem identification, involves gaining awareness that inconsistencies exist between the current state of a situation and the desired circumstances. At this level the decision maker tries to diagnose the problems that need to be addressed and/or

In the design phase, a decision maker attempts to generate alternatives, and analyses the options to provide knowledge about their relevant implications. During this phase, the decision maker may find that supplementary knowledge is required. This leads to a return to the

During the choice phase, the decision maker selects one of the proposed alternatives that have been explored in the design phase. The outcome depends on the nature of the decision context

intelligence stage to clarify the problems before continuing with the design activity [6].

There is a variety of decision types which can be classified based on specific factors. An appreciation of decision types can assist decision makers understand what knowledge and knowledge manipulation features would be required in decision support system [6]. The level of "programmability" or structuredness is a helpful aspect for understanding and classifying decisions. Simon argued that decisions could be placed along a spectrum from highly structured to completely unstructured [23]. Decisions may also be further classified as single-stage and multiple-stage, with either risk, certainty or uncertainty of outcome.

Structured decisions are made when well-known procedures can be readily applied to all the phases of decision-making to provide standard solutions for repetitive problems. They are characterized by definite decision criteria, a limited number of precise alternatives whose consequences can be worked out without any complexity [24].

Table 1. Decision structuredness [6].

A semi-structured decision is made when some, but not all, of the phases of decision-making are structured. While some standard solution procedures may be applicable, human judgment is also called upon to develop decisions which tend to be adaptive in nature [1].

When none of the phases of decision-making are structured, the resulting decisions are classified as unstructured. Lack of clear decision criterion and the difficulty in identifying a finite set of alternatives and high levels of uncertainty concerning the consequences of the known alternatives at most of the decision levels, are all symptoms of this unstructuredness [25].

Semi-structured and unstructured decisions are made when problems are ill-defined (illstructured). Srinivasan et al. notes that most real-world problems fall towards the unstructured end of this spectrum [20]. Table 1 demonstrates the characteristics of structured and unstructured decisions.