Sex Estimation of Medial Aspect of the Ischiopubic Ramus in Adults Based on Deep Learning / 法医学杂志

OBJECTIVES@#To investigate the reliability and accuracy of deep learning technology in automatic sex estimation using the 3D reconstructed images of the computed tomography (CT) from the Chinese Han population.@*METHODS@#The pelvic CT images of 700 individuals (350 males and 350 females) of the Chinese Han population aged 20 to 85 years were collected and reconstructed into 3D virtual skeletal models. The feature region images of the medial aspect of the ischiopubic ramus (MIPR) were intercepted. The Inception v4 was adopted as the image recognition model, and two methods of initial learning and transfer learning were used for training. Eighty percent of the individuals' images were randomly selected as the training and validation dataset, and the remaining were used as the test dataset. The left and right sides of the MIPR images were trained separately and combinedly. Subsequently, the models' performance was evaluated by overall accuracy, female accuracy, male accuracy, etc.@*RESULTS@#When both sides of the MIPR images were trained separately with initial learning, the overall accuracy of the right model was 95.7%, the female accuracy and male accuracy were both 95.7%; the overall accuracy of the left model was 92.1%, the female accuracy was 88.6% and the male accuracy was 95.7%. When the left and right MIPR images were combined to train with initial learning, the overall accuracy of the model was 94.6%, the female accuracy was 92.1% and the male accuracy was 97.1%. When the left and right MIPR images were combined to train with transfer learning, the model achieved an overall accuracy of 95.7%, and the female and male accuracies were both 95.7%.@*CONCLUSIONS@#The use of deep learning model of Inception v4 and transfer learning algorithm to construct a sex estimation model for pelvic MIPR images of Chinese Han population has high accuracy and well generalizability in human remains, which can effectively estimate the sex in adults.

Research Progress of Age Estimation in the Living by Knee Joint MRI / 法医学杂志

Bone development shows certain regularity with age. The regularity can be used to infer age and serve many fields such as justice, medicine, archaeology, etc. As a non-invasive evaluation method of the epiphyseal development stage, MRI is widely used in living age estimation. In recent years, the rapid development of machine learning has significantly improved the effectiveness and reliability of living age estimation, which is one of the main development directions of current research. This paper summarizes the analysis methods of age estimation by knee joint MRI, introduces the current research trends, and future application trend.

Interpretation and comparison of international guidelines for salivary gland malignancy in 2021 / 中华口腔医学杂志

In order to provide evidence-based recommendations on the management of salivary gland malignancy (SGM), the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) formulated and updated SGM clinical practice guidelines respectively in 2021.The two guidelines are interpreted and compared in this article from six perspectives including preoperative evaluations, surgical diagnostic and therapeutic procedures, appropriate radiotherapy techniques, the role of systemic therapy, follow-up evaluations and recurrent-metastatic diseases' management of SGM, which has guiding significance for diagnosis and treatment of SGM in China.

Primary cell culture and morphological observation of bulbar conjunctival fibroblasts in conjunctivochalasis / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the growth status and morphological changes of primary cultured bulbar conjunctival fibroblasts in different stages of conjunctivochalasis(CCH), and to determine the best passage time, so as to obtain stable and consistent CCH bulbar conjunctival fibroblasts.METHODS: CCH primary bulbar conjunctival fibroblasts were obtained by tissue block adhesion method. The fibroblasts were purified by trypsin differential digestion method. The growth status and morphological changes of fibroblasts in different periods were observed and recorded under inverted microscope. The fibroblasts were identified by immunofluorescence cytochemical staining.RESULTS: After 24h of CCH conjunctival tissue adherent to the wall, a small number of cells would be seen crawling out around the tissue blocks. The logarithmic phase of cell growth was from the 2-7d. The cells grew fast, with vigorously proliferation, clear outline, uniform distribution, increas in numbers and clear nuclei. From the 9-15d, the cell growth entered the plateau stage, the tissue blocks gradually aged and lost activity. The cells grew slowly, arranged loosely, the volume became larger, the shape became flat, and a large number of granular substances and vesicles were produced in the cytoplasm. Some cells fell off from the bottom of the culture bottle, and large gaps appeared between the cells. After subculture and purification, the size and morphology of fibroblasts were basically the same. Through cell identification, fibroblasts were long spindle, flat star or multi-process spindle, wide in the middle, oval nucleus, relatively small at both ends, with 2-3 slender processes of different lengths extending outward.CONCLUSION: Primary CCH bulbar conjunctival fibroblasts can be successfully obtained by tissue block adhesion method. When the cells grow to the 8d, they can be digested and passaged to obtain stable and consistent CCH conjunctival fibroblasts.

Research Status of Postmortem MSCT Angiography in Forensic Science / 法医学杂志

Virtual autopsy is a new technique for investigating the morphological changes of cadaveric tissues and organs by medical imaging technology. It has been widely used in the identification of causes of death. Multislice spiral computed tomography （MSCT） has become a routine inspection method in some identification institutions, although it cannot completely replace traditional autopsy, it plays a key auxiliary or substitute role in the identification of certain abnormal causes of death. Plain MSCT scan cannot visualize cadaveric vessels, but can perform cadaveric angiography to determine vascular injury or disease. This technology has entered a rapid development period in recent years, and has made a considerable progress in contrast agent, perfusion methods and imaging methods. This article summarizes several common cadaveric MSCT angiography methods, such as systemic angiography, angiography through cardiopulmonary resuscitation, targeted angiography, and angiography by cardiac puncture, and analyzes and compares the application prospects.

Establishment of Mathematical Models for Skeletal Age Determination of Extremitas Sternalis of Clavicle in Shanxi Adolescents / 法医学杂志

Objective To develop mathematical models for skeletal age determination with multiple statistic method based on the correlation between age and the growth of the epiphysis of extremitas sternalis of clavicle in Shanxi adolescents. Methods The 562 Shanxi sternoclavicular joint samples （454 cases of modelling, 108 cases of external verification） were scanned by the thin-section computed tomography. After volume rendering was obtained, indicators such as area of epiphysis, area of metaphysis, longest diameter of epiphysis and longest diameter of metaphysis of both extremitas sternalis of clavicle were collected. Indicators such as the ratio of area of epiphysis to area of metaphysis, and the ratio of longest diameter of epiphysis to longest diameter of metaphysis of both sides were calculated. Then multiple linear regression and random forest discriminant models were used to build mathematical models for age determination of adolescents. Results The obtained indicators exhibited a strong correlation with age （r>0.85）. The multiple linear regression model for males and females （all 4 indicators entering the model） based on the ratio of longest diameter of epiphysis to longest diameter of metaphysis and the ratio of area of epiphysis to area of metaphysis had an internal validation accuracy rate （±1.0 year） of over 92% and 108 cases had an external validation accuracy rate of over 70% （±1.0 year）. The out of bag error rates of random forest discriminant models were less than 2% for people over 18.0 years old （≥18.0 years old） and under 18.0 years old. The external validation accuracy rates of the 108 cases were over 80%. Conclusion The regression and discriminant models established in this study have certain reliability and accuracy and can be used in age determination of Shanxi adolescents.

Comparison of Three CNN Models Applied in Bone Age Assessment of Pelvic Radiographs of Adolescents / 法医学杂志

Objective To compare the performance of three deep-learning models （VGG19, Inception-V3 and Inception-ResNet-V2） in automatic bone age assessment based on pelvic X-ray radiographs. Methods A total of 962 pelvic X ray radiographs taken from adolescents （481 males, 481 females） aged from 11.0 to 21.0 years in five provinces and cities of China were collected, preprocessed and used as objects of study. Eighty percent of these X ray radiographs were divided into training set and validation set with random sampling method and used for model fitting and hyper-parameters adjustment. Twenty percent were used as test sets, to evaluate the ability of model generalization. The performances of the three models were assessed by comparing the root mean square error （RMSE）, mean absolute error （MAE） and Bland-Altman plots between the model estimates and the chronological ages. Results The mean RMSE and MAE between bone age estimates of the VGG19 model and the chronological ages were 1.29 and 1.02 years, respectively. The mean RMSE and MAE between bone age estimates of the Inception-V3 model and the chronological ages were 1.17 and 0.82 years, respectively. The mean RMSE and MAE between bone age estimates of the Inception-ResNet-V2 model and the chronological ages were 1.11 and 0.84 years, respectively. The Bland-Altman plots showed that the mean value of differences between bone age estimates of Inception-ResNet-V2 model and the chronological ages was the lowest. Conclusion In the automatic bone age assessment of adolescent pelvis, the Inception-ResNet-V2 model performs the best while the Inception-V3 model achieves a similar accuracy as VGG19 model.

Research Progress and Prospect of Machine Learning in Bone Age Assessment / 法医学杂志

Bone age assessment has always been one of the key issues and difficulties in forensic science. With the gradual development of machine learning in many industries, it has been widely introduced to imageology, genomics, oncology, pathology, surgery and other medical research fields in recent years. The reason why the above research fields can be closely combined with machine learning, is because the research subjects of the above branches of medicine belong to the computer vision category. Machine learning provides unique advantages for computer vision research and has made breakthroughs in medical image recognition. Based on the advantages of machine learning in image recognition, it was combined with bone age assessment research, in order to construct a recognition model suitable for forensic skeletal images. This paper reviews the research progress in bone age assessment made by scholars at home and abroad using machine learning technology in recent years.

Evaluation and Countermeasures of the Implementation of Forensic Clinical Identification Standards Based on the Perspective of Accreditation / 法医学杂志

The new Standardization Law, implemented in 2018, has added a standard post-implementation evaluation system, aiming to continuously improve the quality of standards through post-implementation evaluation. Standards in the forensic science field are closely related to accreditation activities. Forensic science standards are not only the criteria on which accreditation activities are carried out, but also one of the key contents of the inspection of forensic science institutions in accreditation activities. Since 2018, the certification and accreditation policies in the forensic science field have also been changed, which has brought impacts on the construction of a standard system based on accreditation.This paper analyzes the standard data from China National Accreditation Center from Conformity Assessment on forensic clinical identification accreditation assessment. It points out that the current coverage of laboratory accreditation activities is limited, the development in different provinces is unbalanced, and there is overlap and crossover in the standards in use. It is emphasized that the construction of the national forensic science standardization technical committee, the improvement of the forensic science standard system, the establishment of the standard implementation evaluation index system, and promotion of the coordination of standards, and the certifications and accreditations should be accelerated, in order to continue to promote the standardization and accreditation activities in the field of forensic science.

Regression Algorithm of Bone Age Estimation of Knee-joint Based on Principal Component Analysis and Support Vector Machine / 法医学杂志

Objective To establish a regression algorithm model that applies to bone age estimation of Xinjiang Uygur adolescents with machine learning methods such as histogram of oriented gradient （HOG）, local binary patterns （LBP）, support vector machine （SVM）, principal component analysis （PCA）. Methods DR images of knee-joints from 275 male and 225 female subjects aged 12.0-<19.0 years old were collected, PCA method was used to reduce the dimensionality of the HOG and LBP features, and support vector regression （SVR） was used to establish a knee-joint bone age estimation algorithm model. Stratified random sampling method was used to select 215 male samples, 180 female samples for the model training set. K-fold cross validation method was used to optimize parameters of the model. The remaining samples as the independent test set was used to compare the sample's true age and model estimated age, and had an accuracy rate in the statistical error range of ±0.8 and ±1.0 years, respectively. Then the mean absolute error （MAE） and root mean square error （RMSE） were calculated. Results The accuracy rate of male in the statistical error range of ±0.8 and ±1.0 year was 80.67%, 89.33%, respectively. The MAE and RMSE were 0.486 and 0.606 years, respectively. The accuracy rate of female in the statistical error range of ±0.8 and ±1.0 years was 80.19%, 90.45%, respectively. The MAE and RMSE were 0.485 and 0.590 years, respectively. Conclusion Establishment of prediction model for bone age estimation by feature dimension reduction of HOG and LBP in DR images of knee-joint based on PCA and SVM has relatively high accuracy.

Automated Assessment for Bone Age of Left Wrist Joint in Uyghur Teenagers by Deep Learning / 法医学杂志

Objective To realize the automated bone age assessment by applying deep learning to digital radiography(DR)image recognition of left wrist joint in Uyghur teenagers, and explore its practical ap-plication value in forensic medicine bone age assessment. Methods The X-ray films of left wrist joint after pretreatment, which were taken from 245 male and 227 female Uyghur nationality teenagers in Uygur Autonomous Region aged from 13.0 to 19.0 years old, were chosen as subjects. And AlexNet was as a regression model of image recognition. From the total samples above, 60% of male and fe-male DR images of left wrist joint were selected as net train set, and 10% of samples were selected as validation set. As test set, the rest 30%were used to obtain the image recognition accuracy with an error range in ±1.0 and ±0.7 age respectively, compared to the real age. Results The modelling results of deep learning algorithm showed that when the error range was in ±1.0 and ±0.7 age respectively, the accuracy of the net train set was 81.4% and 75.6% in male, and 80.5% and 74.8% in female, respectively. When the error range was in ±1.0 and ±0.7 age respectively, the accuracy of the test set was 79.5% and 71.2% in male, and 79.4% and 66.2% in female, respectively. Conclusion The combination of bone age research on teenagers' left wrist joint and deep learning, which has high accuracy and good feasi-bility, can be the research basis of bone age automatic assessment system for the rest joints of body.

Advantages and Application Prospects of Deep Learning in Image Recognition and Bone Age Assessment / 法医学杂志

Deep learning and neural network models have been new research directions and hot issues in the fields of machine learning and artificial intelligence in recent years. Deep learning has made a breakthrough in the applications of image and speech recognitions, and also has been extensively used in the fields of face recognition and information retrieval because of its special superiority. Bone X-ray images express different variations in black-white-gray gradations, which have image features of black and white contrasts and level differences. Based on these advantages of deep learning in image recognition, we combine it with the research of bone age assessment to provide basic datum for constructing a forensic automatic system of bone age assessment. This paper reviews the basic concept and network architectures of deep learning, and describes its recent research progress on image recognition in different research fields at home and abroad, and explores its advantages and application prospects in bone age assessment.

Meta-analysis of Yiqi Huoxue method in treating idiopathic membranous nephropathy / 中国中药杂志

The incidence of idiopathic membranous nephropathy (IMN) is increasing year by year, and the clinical research on Chinese medicine treatment of INM is also growing. This study aims to evaluate the efficiency and safety of Yiqi Huoxue method for IMN. Data sources used were from PubMed, EMbase, the Cochrane Library, CBM, CNKI, Wanfang and VIP database. Two researchers independently screened the literature and extracted data. RevMan 5.3 software was used for Meta analysis, and the evidences were graded for the outcomes according to GRADE system by using GRADEprofiler 3.6. Eventually, eleven trials (725 participants) were included in the Meta-analyses. There was statistically significant difference between Yiqi Huoxue method and controls when combining all trials in 24 h UTP [RR=-1.23, 95%CI=(-1.94,-0.53), P=0.000 6] or when combining all trials in ALB [RR=3.56, 95%CI=(1.64, 5.47), P=0.000 3]. Meanwhile, there was statistically significant difference between Yiqi Huoxue method and controls when combining all trials in TC [RR=-0.39, 95%CI=(-0.57, -0.20), P<0.000 1] or when combining all trials in TG [RR=-0.49, 95%CI=(-0.82, -0.15), P=0.004]. However, there was no statistically significant difference between Yiqi Huoxue method and controls when combining all trials in Scr [RR=-3.25, 95%CI=(-9.35, 2.84), P=0.30] or when combining all trials in BUN [RR=-0.81,95%CI=(-2.29, 0.66), P=0.28]. In the statistics, the most frequently used Chinese medicines in clinical application were Astragali Radix, Angelicae Sinensis Radix, Chuanxiong Rhizoma, Codonopsis Radix, Atractylodis Macrocephalae Rhizome and Salvia Miltiorrhiza. The present evidences suggested that Yiqi Huoxue method should be thought highly of in the treatment of IMN, and at the same time, the rational use of traditional Chinese medicine, such as Astragali Radix, Angelicae Sinensis Radix, Chuanxiong Rhizoma also should be paid attention to. However, due to the GRADE evidence grading of the primary outcome measure of 24 h UTP had very low quality, this review can not provide high-quality evidence to prove the clinical efficacy of this method. More well-designed and large-scale multi-center randomized controlled trials should be conducted in the future for verification.

Coronary angiography of in vitro porcine heart using MSCT / 法医学杂志

OBJECTIVE@#To establish standardized methods and parameters of the isolated heart coronary angiography through the experiment of in vitro porcine heart by MSCT.@*METHODS@#Based on different perfusion volume (50, 60 and 70 mL) and different perfusion-imaging time (5, 10 and 20 min), the in vitro porcine coronary artery was injected liposoluble and water-soluble contrast agents using remodel angiography equipment and scanned by MSCT. And the 3D image results were compared. The images were recorded and evaluated by 2 radiologists and analyzed by statistical software.@*RESULTS@#Liposoluble contrast agent affected the images by damaging and infiltrating the fats around the coronary artery, while the water-soluble contrast agent didn't affect the images. The groups with 60 mL or 70 mL perfusion and 5 min perfusion-imaging time had the best images.@*CONCLUSION@#The suitable parameters of the angiography lay the foundation of postmortem coronary angiography.

Automated assessment of developmental levels of epiphysis by support vector machine / 法医学杂志

OBJECTIVE@#To realize the automated assessment of the levels of epiphysis of distal radius and ulna by support vector machine (SVM).@*METHODS@#The X-ray films of the left wrist joints were taken from 140 teenagers aged from 11 to 19 years old as training samples. The levels of epiphysis of distal radius and ulna were divided into five developmental levels. Each level contained 28 samples. Another 35 cases were selected as independent verifying samples. SVM classification models of the five developmental levels of epiphysis of distal radius and ulna were established. The internal cross validation was made by leave one out cross validation (LOOCV), while the external validation was made by histogram of oriented gradient (HOG), and then the accuracy (PA) of testing results was calculated, respectively.@*RESULTS@#The PA of SVM, LOOCV and HOG of distal radius epiphyseal level were 100%, 78.6%, and 82.8%, respectively; whereas the PA of SVM, LOOCV and HOG of distal ulna epiphyseal level were 100.0%, 80.0% and 88.6%, respectively.@*CONCLUSION@#The SVM-based automatic models of the growth stage of distal ra- dius and ulna appear to have certain feasibility, and may provide a foundation for software development of bone age assessment by forensic medicine.

Application of MSCT's coronary artery calcification score in evaluation of sudden death caused by coronary artery disease / 法医学杂志

OBJECTIVE@#To access application value of multi-slice spiral computed tomography (MSCT) and coronary artery calcium scoring (CACS) in investigation the coronary artery disease (CAD), and to explore the effective way of virtual autopsy to evaluate the sudden death due to CAD.@*METHODS@#Nine cases of sudden cardiac death were collected to analyze MSCT before the autopsy. The quantitative analysis of the degree of coronary artery calcium was made by Agatston's method. The CACS of all the subjects were calculated based on the diagnostic criteria for CAD, in which calcium scoring was more than 400. The results of CACS were compared with that of the autopsy.@*RESULTS@#Only 2 cases got the high calcium scoring which were more than 400 in the 9 cases died of CAD confirmed by the autopsy. The prediction rate of CACS for CAD was only 22.2%. Pulmonary edema of different severity was found in both autopsy and MSCT. There was a higher morbidity rate in the left anterior descending of coronary artery than the other branches.@*CONCLUSION@#Obvious calcification of coronary artery can be detected by MSCT and calculating CACS. To detect subtle calcification needs other technologies such as postmortem angiography.

Mathematical models of the teenager's skeletal age evaluation based on CT scan and imaging reconstruction of medial clavicular epiphysis / 法医学杂志

OBJECTIVE@#To explore the correlation between CT volume rendering (VR) statistics and living age and to build the mathematical models for skeletal age evaluation based on the growth rules of medial clavicular epiphysis of teenagers in China.@*METHODS@#The thin layer CT scan and VR 3D imaging reconstruction of both sides of sternal ends of clavicles were examined for 684 teenagers aged from 15 to 25 in East and South China. The parameters of sternal end of clavicle including the longest diameter of epiphysis, the longest diameter of metaphysis, their length radio, area of epiphysis, area of metaphysic, their area ratio, and other data were measured and calculated in order to establish mathematical models of skeletal age evaluation. Fifty trained subjects were tested to verify the accuracy of the mathematical models.@*RESULTS@#In the same age group, the length ratio and the area ratio had significant difference in genders (P < 0.05). The established mathematical models showed that the growth rules of medial clavicular epiphysis were highly correlated with the living ages. The accuracies of these models were higher than 70.5% +/- 1.0 year) and 82.5% (+/- 1.5 year).@*CONCLUSION@#The mathematical models have easy operability and high accuracy. It can be used to confirm and sustain the conclusion of atlas method. Meanwhile, it is of great significance to study the other single skeletal age evaluation in the future.

Mathematical models for teenager's living age evaluation based on CT image of medial clavicular epiphysis / 法医学杂志

OBJECTIVE@#To explore the correlation between volume rendering (VR) statistics of medial clavicular epiphysis and living age, and establish the mathematical models for living age evaluation using the CT image of medial clavicular epiphysis based on the growth rules of osteoepiphysis of medial clavicle.@*METHODS@#The CT images of the medial clavicles from 795 teenagers aged 15-25, 387 males and 408 females, were collected in East and South China. VR 3D images were reconstructed from 0.60 mm-thick slice CT images. The epiphyseal diameter, sternal end diameter, and their respective diameter ratio (the left: X1; the right: x3); epiphyseal area, sternal end area, and their respective area ratio (the left: x2; the right: x4), were measured and calculated. All these observations were analyzed using SPSS 19.0 statistical software. The statistical differences in gender and age were analyzed by Mann-Whitney U test. The mathematical models were established using least square. Sixty trained subjects, 30 males and 30 females, were tested to verify the accuracy of the established mathematical models.@*RESULTS@#In the group of same age, x1 showed significant difference in gender; the same results were observed in x2, x3, and x4, which suggested that the growth rules of osteoepiphysis of medial clavicle were highly correlated with living age. The accuracy of these mathematical models were all above 67.6% (+/- 1.0 year) and 78.5% (+/- 1.5 year).@*CONCLUSION@#The mathematical models with reasonable accuracy could be manageable in practice to confirm the conclusion of the atlas method. The current study can contribute to the single skeletal age evaluation.

Bone development trend in the knee joint of Tibetan teenagers in Aba Prefecture of Sichuan Province / 法医学杂志

OBJECTIVE@#To discuss bone development trend in the knee joint of Tibetan teenagers in Sichuan province and to effectively update the database for estimating the living age of Tibetan teenagers in terms of bone age of the knee joint.@*METHODS@#Radiographs including epiphysis of distal femur, proximal tibia and proximal fibula were taken from 483 Tibetan male and female teenagers aged from 14 to 19 years old in Aba prefecture of Sichuan province in order to observe epiphyseal growth situation. The descriptive data of the epiphyseal closure ages of these teenagers' knee joints were statistically analyzed by SPSS 16.0 software.@*RESULTS@#The distal femur epiphyseal closure occurred earliest, while the proximal fibula epiphyseal closure occurred latest. The epiphyseal growth of knee joints of females occurred about one year earlier than that of males.@*CONCLUSION@#The forensic information and data related to Tibetan teenagers' bone age identification should be updated regularly. These results provide potential value for the practice of forensic medicine, anthropology and clinical medicine.

The staging method of sternal end of clavicle epiphyseal growth by thin layer CT scan and imaging reconstruction / 法医学杂志

OBJECTIVE@#To establish a CT staging method of sternal end of clavicle epiphyseal growth for teenagers by thin layer CT scan, multiplanar reconstruction (MPR) and volume reconstruction (VR) technologies.@*METHODS@#The CT imaging characteristics, which collected from 460 teenagers (aged from 15 to 25) in East and South China, were studied through both sternal ends of clavicles' imagings by thin layer coronal CT scan and axial CT scan, MPR and VR technologies. The parameters of sternal end of clavicle including the longest diameter of epiphysis, the longest diameter of metaphysis, their length ratio, area of epiphysis, area of metaphysis, and their area ratio were measured and calculated in order to establish new classification.@*RESULTS@#Based on the staging method of Schmeling, integrating the CT imaging reconstruction information of sternal end of clavicle, the new classification of sternal end of clavicle epiphyseal growth were divided into 1 to 5 stages, and stage 2 and stage 3, respectively, contained a, b and c sub-classification.@*CONCLUSION@#This new classification has merits of large sample size, wide age range and easy operability. By using CT imaging reconstruction techniques and analyzing the data which closely related to sternal end of clavicle epiphyseal growth of teenagers, the feasibility of the staging method could be increased.