Method and device for prehypertension prediction and risk feature description
Through the multi-layer perceptron model and support vector machine model optimized by particle swarm algorithm in hypertension prediction, combined with SHAP value analysis, the problems of data set imbalance and insufficient variable selection in the prior art were solved, and the prediction accuracy of early hypertension and the accuracy of risk characteristics were improved.
Patent Information
- Application Number
- CN202510073771.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-01-17
- Publication Date
- 2025-05-13
AI Technical Summary
The existing machine learning-based hypertension prediction methods have shortcomings in the problems of data set imbalance and insufficient variable selection, which affects its accuracy and effectiveness.
A multi-layer perceptron model (PSO-MLP) optimized based on particle swarm algorithm is used, and the risk prediction and risk feature description of pre-hypertension is combined with the support vector machine (SVM) model, and the contribution of each feature is analyzed through SHAP value calculation and visualization.
It improves the accuracy of prediction of pre-hypertension and the accuracy of risk characteristics description, can more effectively identify high-risk groups and provide personalized medical advice.
Smart Images
Figure CN119993486A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to a method for predicting pre-hypertension and describing risk characteristics based on a particle swarm algorithm-optimized multi-layer perceptron model, and also relates to a corresponding device for predicting pre-hypertension and describing risk characteristics, belonging to the field of artificial intelligence-assisted diagnosis technology. Background Art
[0002] Hypertension is a huge challenge facing the global public health field. It is an important influencing factor for cardiovascular and cerebrovascular diseases, kidney diseases, etc. It is also a preventable factor for cerebrovascular disease burden and mortality. The risk factors for hypertension come from a wide range of sources and types, and the interaction between different characteristics must be considered.
[0003] Existing studies on hypertension are all based on the 140 / 90 standard. In recent years, there has been a wave of discussion on the standard of hypertension in China. In 2017, the standard of hypertension in the United States was lowered to 130 / 80, and similar suggestions have also appeared in China. In 2024, the Chinese Society of Cardiology, the Hypertension Professional Committee of the Cross-Strait Medical and Health Exchange Association, and the Cardiovascular Disease Prevention and Rehabilitation Professional Committee of the Chinese Rehabilitation Medicine Association jointly initiated the formulation of the "Chinese Hypertension Clinical Practice Guidelines", which recommended that a systolic blood pressure of 130-139 mmHg and (or) a diastolic blood pressure of 80-89 mmHg be considered prehypertension. Prehypertension can also cause an increase in the incidence of cardiovascular and cerebrovascular events. Predicting the occurrence of prehypertension is an important method to prevent hypertension in advance and reduce the probability of hypertension.
[0004] At present, artificial intelligence (AI) technology is booming, and its potential in medical auxiliary diagnosis, auxiliary risk assessment, etc. is constantly emerging. Machine learning uses algorithms to learn and summarize patterns, and can build models such as decision trees, random forests, gradient boosting trees, support vector machines, etc. It is a method widely used in probability prediction and is capable of classifying and predicting hypertension.
[0005] Most of the existing machine learning-based hypertension prediction methods use balanced data sets, which affects the performance and accuracy of the model. In addition, most of the variables included in the existing prediction methods are based on established aspects and some basic characteristics, and the influencing factors of hypertension are not considered enough. These factors have an impact on the accuracy of machine learning prediction of hypertension, which is still a problem that needs to be solved urgently. Summary of the invention
[0006] The primary technical problem to be solved by the present invention is to provide a method for predicting prehypertension and describing risk characteristics.
[0007] Another technical problem to be solved by the present invention is to provide a device for predicting pre-hypertension and describing risk characteristics.
[0008] In order to achieve the above object, the present invention adopts the following technical solutions:
[0009] A method for predicting the risk of prehypertension and describing risk characteristics comprises the following steps:
[0010] Step S1, obtaining data to be collected, the data to be collected as survey data, specifically including demographic data, dietary data, physical examination data, and laboratory examination data of the subject;
[0011] Step S2, inputting the data to be collected into a pre-trained prehypertension risk prediction model and a risk characteristic description model, and using the data to be collected, i.e., the survey data, as risk characteristics for prediction and description;
[0012] Step S3, the output result of the prehypertension risk prediction model is the probability of prehypertension of the subject, and the output result of the risk characteristic description model is the most dangerous factor of the subject at present;
[0013] Step S4: Calculate the SHAP value, analyze the risk characteristic status of the person to be investigated, and visualize it.
[0014] Specifically, when obtaining the demographic data:
[0015] Step 111: For age and race, the ordered categorical variables are discretized into linear variables, and the unordered binary variables are converted into 0 / 1; the data are further standardized to between 0 and 1 to prevent errors caused by dimensional differences between different variables.
[0016] Specifically, when obtaining the dietary data:
[0017] Step 121, among the total dietary intake on the first day, the total dietary intake on the second day, hexane, vitamin A, magnesium, octadecane, niacin, alcohol content, octane, calcium, folic acid, eicosatetraenoic acid, zinc, retinol, protein, and butane, the ordered categorical variables are discretized into linear, and the unordered binary variables are converted into 0 / 1; the data are further standardized to between 0 and 1 to prevent errors caused by dimensional differences between different variables.
[0018] Specifically, when obtaining the physical examination data:
[0019] Step 131: For weight, body mass index, and thigh length, the ordered categorical variables are discretized into linear variables, and the unordered binary categorical variables are converted into 0 / 1; the data are further standardized to between 0 and 1 to prevent errors caused by dimensional differences between different variables.
[0020] Specifically, when obtaining the laboratory test data:
[0021] Step 141: For total cholesterol and direct high-density lipoprotein cholesterol, the ordered categorical variables are discretized into linear variables, and the unordered binary variables are converted into 0 / 1; the data are further standardized to between 0 and 1 to prevent errors caused by dimensional differences between different variables.
[0022] Preferably, the prehypertension risk prediction model is obtained through the following steps:
[0023] Step S21, obtaining survey data, each set of survey data is demographic data, dietary data, physical examination data, and laboratory examination data of a certain respondent;
[0024] After data cleaning and response variables, the variables with variances that meet the requirements are eliminated through variance selection method;
[0025] Pearson correlation coefficients between systolic and diastolic blood pressure and various variables were calculated to screen out variables related to systolic and diastolic blood pressure. The OR value of each feature's effect on prehypertension was calculated using logistic regression, and statistically significant features were screened out based on the corresponding P values.
[0026] The variables obtained through correlation screening are merged and deduplicated to obtain the initial feature set to reduce false negatives; the variables obtained through correlation screening are passed into the wrapper, and the feature importance is calculated and extracted based on LASSO, XGBoost, and Ranger, and the joint importance is calculated, and the features with a joint importance of 0.5 are included in the model; correlation analysis is performed on the screened features to remove redundant features, and the SMOTE method is used for oversampling. The multivariate logistic regression method is used to explore interaction terms and adopt a better model that incorporates interactions;
[0027] Step S22, obtaining multiple groups of normal and prehypertension survey data, and dividing them into training sets, validation sets and test sets;
[0028] The pre-designed prehypertension risk prediction model was trained using the training samples, and the SMOTE method was used to oversample the balanced dataset and extensively explore the correlation of risk features.
[0029] Use validation samples to verify the model to observe the model fitting status. At the same time, use the particle swarm optimization method to obtain a series of optimized hyperparameters, and bring the hyperparameters into the model for retraining.
[0030] And use the pre-segmented test samples to verify the model accuracy and precision to meet the requirements.
[0031] Preferably, the prehypertension risk prediction model is a multi-layer perceptron model optimized based on a particle swarm algorithm, adopts a fully connected layer stacking structure, and uses a Dropout layer for regularization; the model complexity is reduced by adjusting the number of nodes in the middle layer; the last Dense layer uses a sigmoid activation function to output a probability for a binary classification problem, including 5 Dense layers and 3 Dropout layers, and the 5 Dense layers are specifically as follows:
[0032] The first Dense layer contains 128 nodes, uses the ReLU activation function, has an input shape of 21, and uses L2 regularization, followed by a Dropout layer for regularization to prevent overfitting;
[0033] The second Dense layer contains 64 nodes, uses the ReLU activation function, and uses L2 regularization, followed by a Dropout layer;
[0034] The third Dense layer contains 32 nodes, uses the ReLU activation function, and uses L2 regularization, followed by a Dropout layer;
[0035] The fourth Dense layer contains 16 nodes, uses the ReLU activation function, and uses L2 regularization;
[0036] The last Dense layer contains 1 node and uses the sigmoid activation function for binary classification.
[0037] Preferably, the risk feature description model uses the SVM model for classification prediction. SVM is different from the traditional linear model. SVM uses a kernel function to map data to a high-dimensional space for better classification and is a black box model to a certain extent.
[0038] Preferably, after making a prediction, the prehypertension risk prediction model uses the Shapley method to calculate the SHAP value of each risk feature based on the classification prediction of the SVM model, that is, based on the Shapley value in the cooperative theory, the contribution of each feature to the prediction result is calculated. For each instance, the sum of the SHAP values is equal to the predicted value of the corresponding SVM model output minus the benchmark output. The larger the absolute value of the SHAP value calculated for a feature, the greater the role played by the feature in the prediction of the sample; and the SHAP value of each feature is visualized.
[0039] The present invention also discloses a device for predicting pre-hypertension and describing risk characteristics, including a processor, a storage and a display. The processor reads a computer program in the storage and the result is displayed on the display. The processor is used to execute the method for predicting pre-hypertension and describing risk characteristics.
[0040] Beneficial effects of the present invention
[0041] The present invention uses the SVM model for classification prediction, which is convenient for analyzing the most dangerous factors and screening high-risk groups; and uses the PSO-MLP model for probability prediction to analyze the patient's current risk value of prehypertension, so as to make changes to reduce his risk of disease.
[0042] The present invention uses the SHAP method to provide a reasonable explanation for the black box model, that is, based on the classification prediction of the SVM model, the SHAP value of each feature is calculated according to each sample, which can prompt which factors are risk factors under the patient's current condition and which factor contributes the most to making a positive prediction of prehypertension, making it more convenient to carry out precise and personalized medical treatment.
[0043] During the application process, the collected data is input into the pre-trained prehypertension risk prediction model, which will output the probability of the subject suffering from prehypertension in the range of 0-1, so that when medical conditions are lacking, the subject can be inferred with a certain probability whether he or she is in prehypertension based on the probability of the subject suffering from prehypertension and the conditions for prehypertension. Or the subject can use this model for pre-screening by themselves. If the output probability of this model is greater than 0.5, it means that the subject is more likely to be in prehypertension. This model can output the risk characteristics of the subject, which is helpful to assist in understanding the risk characteristics of the subject and to provide constructive suggestions accordingly.
[0044] In addition, the present invention focuses on classification prediction under the 130 / 80 standard, and provides accurate and personalized guidance and treatment to patients in the early stages of hypertension, so as to achieve early detection, early diagnosis and early treatment of hypertension, which is of great significance for preventing hypertension in advance and reducing the probability of hypertension. BRIEF DESCRIPTION OF THE DRAWINGS
[0045] Figure 1 Schematic diagram of the process of predicting risk of prehypertension and describing risk characteristics provided by the embodiment of the present invention
[0046] Figure 2 Schematic diagram of the structure of the fully connected layer stack used in the prehypertension risk prediction model of the present invention
[0047] Figure 3 Schematic diagram of ROC curve of each model in the embodiment on the validation set
[0048] Figure 4 This is a diagram showing the effect of probability prediction by the PSO-MLP model in the embodiment.
[0049] Figure 5A schematic diagram of the structure of a device for predicting risk of prehypertension and describing risk characteristics provided by an embodiment of the present invention
[0050] Figure 6 Schematic diagram of contribution ranking of risk characteristics of a subject in prehypertension according to an embodiment of the present invention
[0051] Figure 7 Schematic diagram of the interaction between multiple features in an embodiment of the present invention DETAILED DESCRIPTION
[0052] The technical content of the present invention is described in detail below with reference to the accompanying drawings and specific examples.
[0053] For people suspected of prehypertension, in order to help doctors predict patients' (or help patients self-diagnose) prehypertension risk, such as Figure 1 As shown, the method for predicting the risk of prehypertension provided by the embodiment of the present invention comprises the following steps:
[0054] Step S1, obtaining the data to be investigated, which includes the patient's demographic data, dietary data, physical examination data, and laboratory test data. The influencing factors of prehypertension are complex, and various factors are more or less involved, so we collect features on a large scale to increase the accuracy of the model.
[0055] When obtaining the demographic data, the following steps are included:
[0056] Step 111: For age and race, the ordered categorical variables are discretized into linear variables, and the unordered binary variables are converted into 0 / 1 to prevent feature explosion and reduce model complexity. The data is further standardized to between 0 and 1 to prevent errors caused by dimensional differences between different variables.
[0057] When obtaining the dietary data, the following steps are included:
[0058] Step 121, among the total dietary intake on the first day, the total dietary intake on the second day, hexane, vitamin A, magnesium, octadecane, niacin, alcohol content, octane, calcium, folic acid, eicosatetraenoic acid, zinc, retinol, protein, and butane, the ordered categorical variables are discretized into linear, and the unordered binary categorical variables are converted into 0 / 1, for the same reason as above. The data are further standardized to between 0 and 1 to prevent errors caused by dimensional differences between different variables.
[0059] The process of obtaining the physical examination data includes the following steps:
[0060] Step 131: For weight, body mass index, and thigh length, the ordered categorical variables are discretized into linear variables, and the unordered binary variables are converted into 0 / 1, for the same reason as above. The data are further standardized to between 0 and 1 to prevent errors caused by dimensional differences between different variables.
[0061] When obtaining the laboratory test data, the following steps are included:
[0062] Step 141: For total cholesterol and direct high-density lipoprotein cholesterol, the ordered categorical variables are discretized into linear variables, and the unordered binary variables are converted into 0 / 1, for the same reason as above. The data are further standardized to between 0 and 1 to prevent errors caused by dimensional differences between different variables.
[0063] Step S2: input the data to be investigated into a pre-trained prehypertension risk prediction model.
[0064] The pre-trained prehypertension risk prediction model was obtained through the following steps:
[0065] Step S21, using the survey data of the NHANES (National Health and Nutrition Examination Survey) database from 2017 to 2018 to obtain multiple groups of normal and pre-hypertension survey data, each group of survey data is the demographic data, dietary data, physical examination data, and laboratory test data of a certain respondent. And select relevant variables from these data for modeling. Specifically:
[0066] After data cleaning and response variables, the variables with small variance were eliminated through variance selection method;
[0067] Pearson correlation coefficients between systolic and diastolic blood pressure and each variable were calculated to screen out variables related to systolic and diastolic blood pressure. The OR value of each feature on prehypertension (binary variable) was calculated using logistic regression, and statistically significant features were screened out based on the corresponding P values.
[0068] The variables obtained through correlation screening are merged and deduplicated to obtain the initial feature set to reduce false negatives; the variables obtained through correlation screening are passed to the wrapper (R package FeatureSelection), and the feature importance is calculated and extracted based on LASSO, XGBoost, and Ranger, and the joint importance is calculated, and the features with a joint importance of 0.5 are included in the model; correlation analysis is performed on the screened features to remove redundant features, the SMOTE method is used for oversampling, and the multivariate logistic regression method is used to explore interaction terms and adopt a better model that incorporates interaction, such as Figure 7 As shown;
[0069] Step S22: Use the method of obtaining the data to be investigated in step S1 to obtain multiple groups of the above-mentioned investigation data of normal and prehypertension, and divide them into training set, validation set and test set to train the prehypertension risk prediction model. In this process, the SMOTE method is used to oversample the balanced data set, widely explore the correlation of risk features, and further use the feature screening method based on the wrapper to screen features. Finally, the model is built and compared, and it is found that the SVM model can make better classification predictions. The ROC curves of each model on the validation set are as follows: Figure 3 At the same time, the present invention establishes a probability prediction based on the PSO-MLP model, and the prediction results of the model are reliable. Figure 4 shown.
[0070] like Figure 2 As shown in the figure, the pre-designed risk prediction model for prehypertension is a multi-layer perceptron model PSO-MLP optimized based on the particle swarm algorithm. It adopts a fully connected layer stacking structure and uses a Dropout layer for regularization. The model complexity is reduced by adjusting the number of nodes in the middle layer. The last Dense layer uses a sigmoid activation function to output a probability for the binary classification problem. It includes 5 Dense layers (4 hidden layers, 1 output layer) and 3 Dropout layers: the first Dense layer contains 128 nodes, uses the ReLU activation function, the input shape is 21, and uses L2 regularization (weight decay), followed by a Dropout layer for regularization to prevent overfitting; the second Dense layer contains 64 nodes, uses the ReLU activation function, and uses L2 regularization, followed by a Dropout layer; the third Dense layer contains 32 nodes, uses the ReLU activation function, and uses L2 regularization, followed by a Dropout layer; the fourth Dense layer contains 16 nodes, uses the ReLU activation function, and uses L2 regularization; the last Dense layer contains 1 node, uses the sigmoid activation function, and is used for binary classification.
[0071] Taking the method of obtaining the data to be investigated in step S1 as an example, the survey data of 4335 samples is obtained, and a fixed proportion (10%) of training samples is used for model verification to observe the model fitting status. At the same time, a series of optimized hyperparameters are obtained using the particle swarm optimization method, including learning rate, L2 regularization coefficient, and Dropout layer ratio. These hyperparameters are brought into the model for retraining, and the model accuracy and precision are tested using 202 pre-segmented test samples to meet the requirements.
[0072] Step S3, the output result of the prehypertension risk prediction model is the probability that the subject is in prehypertension; the collected data obtained in step S1 is input into the pre-trained prehypertension risk prediction model, and the prehypertension risk prediction model will output the probability of the subject suffering from prehypertension in the range of 0-1, so that when medical conditions are lacking, the probability of the subject suffering from prehypertension and the conditions for prehypertension can be used to infer whether the subject is in prehypertension with a certain probability. Alternatively, the subject can use this model for pre-screening by themselves. If the output probability of this model is greater than 0.5, it means that the subject is more likely to be in prehypertension.
[0073] The output result of the risk characteristic description model is the risk characteristic of the subject being in the prehypertension stage.
[0074] Step S4: Calculate the SHAP value, analyze the risk characteristic status of the person to be investigated, and rank the contribution of each characteristic. The result is shown in the following example: Figure 6 As shown, it helps to understand the risk characteristics of the subjects and provide constructive suggestions accordingly.
[0075] In order to implement the method for describing the risk characteristics of pre-hypertension provided by the present invention, the present invention also provides a device for predicting the risk of pre-hypertension and describing the risk characteristics for assisting doctors in diagnosis. Figure 5 As shown, the device for predicting risk and describing risk characteristics of prehypertension includes a processor 30, a storage 29 and a display 31. The processor 30 reads the computer program in the storage 29, and the result is displayed on the display 31. The processor 30 is used to execute a method for predicting risk characteristics of prehypertension and describing risk characteristics disclosed in the present invention.
[0076] The specific embodiments described herein are merely examples of the spirit of the present invention. Those skilled in the art may make various modifications or additions to the specific embodiments described or replace them in similar ways, but they will not deviate from the spirit of the present invention or exceed the scope defined by the appended claims.
Claims
1. A method for predicting the risk of prehypertension and describing risk characteristics, characterized in that The steps include: Step S1, obtaining data to be collected, the data to be collected as survey data, specifically including demographic data, dietary data, physical examination data, and laboratory examination data of the subject; Step S2, inputting the data to be collected into a pre-trained prehypertension risk prediction model and risk feature description model, and using the data to be collected, i.e., the survey data, as risk features for prediction and description; Step S3, the output result of the prehypertension risk prediction model is the probability of prehypertension of the subject, and the output result of the risk characteristic description model is the most dangerous factor of the subject at present; Step S4: Calculate the SHAP value, analyze the risk characteristic status of the person to be investigated, and visualize it.
2. The method according to claim 1, characterized in that When obtaining said demographic data: Step 111: For age and race, the ordered categorical variables are discretized into linear variables, and the unordered binary variables are converted into 0 / 1; the data are further standardized to between 0 and 1 to prevent errors caused by dimensional differences between different variables.
3. The method according to claim 1, characterized in that When obtaining the dietary data: Step 121, among the total dietary intake on the first day, the total dietary intake on the second day, hexane, vitamin A, magnesium, octadecane, niacin, alcohol content, octane, calcium, folic acid, eicosatetraenoic acid, zinc, retinol, protein, and butane, the ordered categorical variables are discretized into linear, and the unordered binary variables are converted into 0 / 1; the data are further standardized to between 0 and 1 to prevent errors caused by dimensional differences between different variables.
4. The method according to claim 1, characterized in that When obtaining the physical examination data: Step 131: For weight, body mass index, and thigh length, the ordered categorical variables are discretized into linear variables, and the unordered binary categorical variables are converted into 0 / 1; the data are further standardized to between 0 and 1 to prevent errors caused by dimensional differences between different variables.
5. The method according to claim 1, characterized in that When obtaining the laboratory test data: Step 141: For total cholesterol and direct high-density lipoprotein cholesterol, the ordered categorical variables are discretized into linear variables, and the unordered binary variables are converted into 0 / 1; the data are further standardized to between 0 and 1 to prevent errors caused by dimensional differences between different variables.
6. The method according to claim 1, characterized in that: The prehypertension risk prediction model is obtained through the following steps: Step S21, obtaining survey data, each set of survey data is demographic data, dietary data, physical examination data, and laboratory examination data of a certain respondent; After data cleaning and response variables, the variables with variances that meet the requirements are eliminated through variance selection method; Pearson correlation coefficients between systolic and diastolic blood pressure and various variables were calculated to screen out variables related to systolic and diastolic blood pressure. The OR value of each feature's effect on prehypertension was calculated using logistic regression, and statistically significant features were screened out based on the corresponding P values. The variables obtained through correlation screening are merged and deduplicated to obtain the initial feature set to reduce false negatives; the variables obtained through correlation screening are passed to the wrapper, and the feature importance is calculated and extracted based on LASSO, XGBoost, and Ranger, and the joint importance is calculated, and the features with a joint importance of 0.5 are included in the model; Correlation analysis was performed on the selected features to remove redundant features, SMOTE method was used for oversampling, and multivariate logistic regression method was used to explore interaction terms and adopt the better model incorporating the interaction; Step S22, obtaining multiple groups of normal and prehypertension survey data, and dividing them into training sets, validation sets and test sets; The pre-designed prehypertension risk prediction model was trained using the training samples, and the SMOTE method was used to oversample the balanced dataset and extensively explore the correlation of risk features. Use validation samples to verify the model to observe the model fitting status. At the same time, use the particle swarm optimization method to obtain a series of optimized hyperparameters, and bring the hyperparameters into the model for retraining. And use the pre-segmented test samples to verify the model accuracy and precision to meet the requirements.
7. The method according to claim 1 or 6, characterized in that: The prehypertension risk prediction model is a multi-layer perceptron model optimized based on the particle swarm algorithm. It adopts a fully connected layer stacking structure and uses a Dropout layer for regularization. The model complexity is reduced by adjusting the number of nodes in the middle layer. The last Dense layer uses a sigmoid activation function to output a probability for a binary classification problem, including 5 Dense layers and 3 Dropout layers. The 5 Dense layers are as follows: The first Dense layer contains 128 nodes, uses the ReLU activation function, has an input shape of 21, and uses L2 regularization, followed by a Dropout layer for regularization to prevent overfitting; The second Dense layer contains 64 nodes, uses the ReLU activation function, and uses L2 regularization, followed by a Dropout layer; The third Dense layer contains 32 nodes, uses the ReLU activation function, and uses L2 regularization, followed by a Dropout layer; The fourth Dense layer contains 16 nodes, uses the ReLU activation function, and uses L2 regularization; The last Dense layer contains 1 node and uses the sigmoid activation function for binary classification.
8. The method according to claim 1, characterized in that: The risk feature description model uses the SVM model for classification prediction.
9. The method according to claim 1, characterized in that: After making a prediction, the prehypertension risk prediction model uses the Shapley method to calculate the SHAP value of each risk feature based on the classification prediction of the SVM model, that is, based on the Shapley value in the cooperative theory, the contribution of each feature to the prediction result is calculated. For each instance, the sum of the SHAP values is equal to the predicted value of the corresponding SVM model output minus the benchmark output. The larger the absolute value of the SHAP value calculated for a feature, the greater the role played by the feature in the prediction of the sample; and the SHAP value of each feature is visualized.
10. A device for predicting prehypertension and describing risk characteristics, comprising a processor, a memory and a display, wherein the processor reads a computer program in the memory and the result is displayed on the display, characterized in that The processor is used to execute the method for predicting prehypertension and describing risk characteristics as described in any one of claims 1-9.