AFICILL: a single-cohort, retrospective study on Atrial Fibrillation In Critically ILL patients admitted to a medical sub-intensive care unit: implications for clinical management, outcomes and elaboration of new data-driven models

Introduction: atrial fibrillation (AF) is common among critically-ill patients, who are considered at increased cardioembolic and haemorragic risk. Consequently, anticoagulant therapy might be ineffective or harmful for an excess of haemorragic events which could not be counterbalanced by an adequate reduction of cardioembolic occurrences. Aims: main outcome (MO) was the composite of death or intensive care unit (ICU) transfer in a population of critically-ill subjects admitted to a medical subintensive care unit (sICU); we assessed (i) thromboembolic events (TEE) and major haemorrhages (MH); (ii) current guidelines (GL) adherence and related outcomes; (iii) performance of validated risk scores for TEE and MH; we engineered (iv) new scores adopting machine learning (ML) predicting MO, TEE, MH. Patients and Methods: single-center, retrospective study enrolling all the consecutive AF-affected patients admitted to a sICU for critical illness. Demographic, clinical, therapeutic and laboratoristic data were collected. Performance of CHA2DS2-VASc and HAS-BLED scores was evaluated. GL-adherence and its relationship with outcomes was studied. ML was used to engineer new predictive models. Results: we enrolled 1430 subjects; CHA2DS2-VASc (AUC:0.516;95%CI:0.472-0.560) and HAS-BLED (AUC:0.493;95%CI:0.443-0.543) did not predict TEE or MH; in-hospital warfarin use was associated to increased MO risk (OR:1.73;95%CI:1.06-2.83; p<0.05); low-molecular-weight-heparin use was not associated to an increased MO risk; antiplatelet drugs use was associated to MO risk reduction (OR:0.51;95%CI:0.34-0.78;p<0.002). GL-adherent treatment was associated to TEE risk reduction and MH and MO risk increase; ML identified specific features for MO, TEE, MH: ML-based classifiers outperformed CHA2DS2-VASc (AUC: from 0.516 to 0.90, p<0.0001) and HAS-BLED (AUC: from 0.493 to 0.82, p<0.0001). Discussion: AF-related outcomes cannot be predicted in critically-ill patients with currently validated methods. GL-adherence is associated to a significant TEE reduction, but also to MH and MO increase. ML algorithms can identify the most important features and shape specific scores able to outperform the classical models

Heart Diseases Diagnosis Using Artificial Neural Networks

Information technology has virtually altered every aspect of human life in the present era. The application of informatics in the health sector is rapidly gaining prominence and the benefits of this innovative paradigm are being realized across the globe. This evolution produced large number of patients’ data that can be employed by computer technologies and machine learning techniques, and turned into useful information and knowledge. This data can be used to develop expert systems to help in diagnosing some life-threating diseases such as heart diseases, with less cost, processing time and improved diagnosis accuracy. Even though, modern medicine is generating huge amount of data every day, little has been done to use this available data to solve challenges faced in the successful diagnosis of heart diseases. Highlighting the need for more research into the usage of robust data mining techniques to help health care professionals in the diagnosis of heart diseases and other debilitating disease conditions. Based on the foregoing, this thesis aims to develop a health informatics system for the classification of heart diseases using data mining techniques focusing on Radial Basis functions and emerging Neural Networks approach. The presented research involves three development stages; firstly, the development of a preliminary classification system for Coronary Artery Disease (CAD) using Radial Basis Function (RBF) neural networks. The research then deploys the deep learning approach to detect three different types of heart diseases i.e. Sleep Apnea, Arrhythmias and CAD by designing two novel classification systems; the first adopt a novel deep neural network method (with Rectified Linear unit activation) design as the second approach in this thesis and the other implements a novel multilayer kernel machine to mimic the behaviour of deep learning as the third approach. Additionally, this thesis uses a dataset obtained from patients, and employs normalization and feature extraction means to explore it in a unique way that facilitates its usage for training and validating different classification methods. This unique dataset is useful to researchers and practitioners working in heart disease treatment and diagnosis. The findings from the study reveal that the proposed models have high classification performance that is comparable, or perhaps exceed in some cases, the existing automated and manual methods of heart disease diagnosis. Besides, the proposed deep-learning models provide better performance when applied on large data sets (e.g., in the case of Sleep Apnea), with reasonable performance with smaller data sets. The proposed system for clinical diagnoses of heart diseases, contributes to the accurate detection of such disease, and could serve as an important tool in the area of clinic support system. The outcome of this study in form of implementation tool can be used by cardiologists to help them make more consistent diagnosis of heart diseases

Machine Learning Modelling of Critical Care Patients in the Intensive Care Units

The ICU is a fast-paced data-rich environment which treats the most critically ill patients. On average, over 15 % of patients admitted to the ICU amount in mortality. Therefore, machine learning (ML) is paramount to aiding the optimisation and inference of insight in critical care. In addition, the early and accurate evaluation of the severity at the time of admission is significant for physicians. Such evaluations make patient management more effective as they are more likely to predict whose physical conditions may worsen. Moreover, ML techniques could potentially enhance patients' experience in the clinical setting by providing medical alerts and insight into future events occurring during hospitalisation. The need for interpretable models is crucial in the ICU and clinical setting, as it is vital to explain a decision that leads to any course of action related to an individual patient. This thesis primarily focuses on mortality, length of stay forecasting, and AF classification in critical care. We cover multiple outcomes and modelling methods whilst using multiple cohorts throughout the research. However, the analysis conducted throughout the thesis aims to create interpretable models for each modelling objective. In Chapter 3, we investigate three publicly available critical care databases containing multiple modalities of data and a wide range of parameters. We describe the processes and contemplations which must be considered to create actionable data for analysis in the ICU. Furthermore, we compared the three data sources using traditional statistical and ML methods and compared predictive performance. Based on 24 hours of sequential data, we achieved AUC performances of 79.5% for ICU mortality prediction and a prediction error of approximately 1.3 hours for ICU LOS. In Chapter 4, we investigate a sepsis cohort and conduct three sub-studies. Firstly, we investigated sepsis subtypes and compared biomarkers using traditional modelling methods. Next, we compare our approach to commonly and routinely used scoring systems in the ICU, such as APACHE IV and SOFA. Our tailored approach achieved superior performance with pulmonary and abdominal sepsis (AUC 0.74 and 0.71respectivly), displaying distinct individualities amongst the different sepsis groups. Next, we further expand our analysis by comparing ML methods and inference approaches to our baseline model and ICU acuity scores. We further investigate extending analysis to other outcomes of interest (In-hospital/ICU mortality, In-hospital/ICU LOS) to gain a more holistic view of the sepsis derivatives. This research shows that nonlinear models such as RF and GBM commonly outperformICU scoring, methods such as APACHE IV and SOFA and linear methods such as logistic/linear regression. Lastly, we extend our analysis in a multi-task learning framework for model optimisation and improved predictive performance. Our results showed superior performance with pulmonary, abdominal and renal/UTI sepsis (AUC 0.76, 0.77 and 0.73, respectively). Lastly, Chapter 5 investigates the classification of atrial fibrillation (AF) in long-lead ECG waveforms in sepsis patients. We developed a deep neural network to classify AF ECGs from Non-AF ECG cases in conjunction with refining a method to gain insight from the neural network model. We achieved a predictive performance of 0.99 and 0.89 regarding the test and external validation data. The inference from the model was achieved through the use of saliency maps, dimensionality reduction methods and clustering, utilising the automatic features learned by the developed model. We developed visualisations to help support the inference behind the classification of each ECG prediction. Overall, the research displays a wide range of novelties and unique approaches to solving various outcomes of interest in the ICU. In addition, this research demonstrates the implication of ML applicability in the ICU environment by providing insight and inference to diverse tasks regardless of the level of complexity. With further development, the frameworks and approaches outlined in this thesis have the potential to be used in clinical practice as decision-support tools in the ICU, allowing the automated alert and detection of patient classification, amongst others. The results generated in this thesis resulted in journal publications and medical understanding gained from insight available in the developed ML frameworks

Artificial neural network techniques to investigate potential interactions between biomarkers

High-throughput technologies in biomedical sciences, including gene microarrays, supposed to revolutionise the post-genomic era, have barely met the great expectations they inspired to the biomedical community at first. Current efforts are still focused toward improving the technology, its reproducibility and accuracy. In the meantime, computational techniques for the analysis of the data from these technologies have achieved great progresses and show encouraging results. New approaches have been developed to extract relevant information out from these results. However, important work needs to be further conducted in order to extract even more meaningful and relevant information. These techniques offer great possibilities to explore the overall dynamic held within a living organism. The potential information contained in their output can reveal important leads at deciphering the interconnection, interaction or regulation influences that can exist between several molecules. In front of an increasing interest of the scientific community toward the exploration of these dynamics, some groups have started to develop solutions based on different technologies to extract these information related to interactions. Here we present an Artificial Neural Network-based methodology for the study of interactions in gene transcriptomic data. This will be applied and validated in a breast cancer context

Classification and detection of Critical Transitions: from theory to data

From population collapses to cell-fate decision, critical phenomena are abundant in complex real-world systems. Among modelling theories to address them, the critical transitions framework gained traction for its purpose of determining classes of critical mechanisms and identifying generic indicators to detect and alert them (“early warning signals”). This thesis contributes to such research field by elucidating its relevance within the systems biology landscape, by providing a systematic classification of leading mechanisms for critical transitions, and by assessing the theoretical and empirical performance of early warning signals. The thesis thus bridges general results concerning the critical transitions field – possibly applicable to multidisciplinary contexts – and specific applications in biology and epidemiology, towards the development of sound risk monitoring system

A data fusion-based hybrid sensory system for older people’s daily activity recognition.

Population aged 60 and over is growing faster. Ageing-caused changes, such as physical or cognitive decline, could affect people’s quality of life, resulting in injuries, mental health or the lack of physical activity. Sensor-based human activity recognition (HAR) has become one of the most promising assistive technologies for older people’s daily life. Literature in HAR suggests that each sensor modality has its strengths and limitations and single sensor modalities may not cope with complex situations in practice. This research aims to design and implement a hybrid sensory HAR system to provide more comprehensive, practical and accurate surveillance for older people to assist them living independently. This reseach: 1) designs and develops a hybrid HAR system which provides a spatio- temporal surveillance system for older people by combining the wrist-worn sensors and the room-mounted ambient sensors (passive infrared); the wearable data are used to recognize the defined specific daily activities, and the ambient information is used to infer the occupant’s room-level daily routine; 2): proposes a unique and effective data fusion method to hybridize the two-source sensory data, in which the captured room-level location information from the ambient sensors is also utilized to trigger the sub classification models pretrained by room-assigned wearable data; 3): implements augmented features which are extracted from the attitude angles of the wearable device and explores the contribution of the new features to HAR; 4:) proposes a feature selection (FS) method in the view of kernel canonical correlation analysis (KCCA) to maximize the relevance between the feature candidate and the target class labels and simultaneously minimizes the joint redundancy between the already selected features and the feature candidate, named mRMJR-KCCA; 5:) demonstrates all the proposed methods above with the ground-truth data collected from recruited participants in home settings. The proposed system has three function modes: 1) the pure wearable sensing mode (the whole classification model) which can identify all the defined specific daily activities together and function alone when the ambient sensing fails; 2) the pure ambient sensing mode which can deliver the occupant’s room-level daily routine without wearable sensing; and 3) the data fusion mode (room-based sub classification mode) which provides a more comprehensive and accurate surveillance HAR when both the wearable sensing and ambient sensing function properly. The research also applies the mutual information (MI)-based FS methods for feature selection, Support Vector Machine (SVM) and Random Forest (RF) for classification. The experimental results demonstrate that the proposed hybrid sensory system improves the recognition accuracy to 98.96% after applying data fusion using Random Forest (RF) classification and mRMJR-KCCA feature selection. Furthermore, the improved results are achieved with a much smaller number of features compared with the scenario of recognizing all the defined activities using wearable data alone. The research work conducted in the thesis is unique, which is not directly compared with others since there are few other similar existing works in terms of the proposed data fusion method and the introduced new feature set