EDMON - Electronic Disease Surveillance and Monitoring Network: A Personalized Health Model-based Digital Infectious Disease Detection Mechanism using Self-Recorded Data from People with Type 1 Diabetes

Through time, we as a society have been tested with infectious disease outbreaks of different magnitude, which often pose major public health challenges. To mitigate the challenges, research endeavors have been focused on early detection mechanisms through identifying potential data sources, mode of data collection and transmission, case and outbreak detection methods. Driven by the ubiquitous nature of smartphones and wearables, the current endeavor is targeted towards individualizing the surveillance effort through a personalized health model, where the case detection is realized by exploiting self-collected physiological data from wearables and smartphones. This dissertation aims to demonstrate the concept of a personalized health model as a case detector for outbreak detection by utilizing self-recorded data from people with type 1 diabetes. The results have shown that infection onset triggers substantial deviations, i.e. prolonged hyperglycemia regardless of higher insulin injections and fewer carbohydrate consumptions. Per the findings, key parameters such as blood glucose level, insulin, carbohydrate, and insulin-to-carbohydrate ratio are found to carry high discriminative power. A personalized health model devised based on a one-class classifier and unsupervised method using selected parameters achieved promising detection performance. Experimental results show the superior performance of the one-class classifier and, models such as one-class support vector machine, k-nearest neighbor and, k-means achieved better performance. Further, the result also revealed the effect of input parameters, data granularity, and sample sizes on model performances. The presented results have practical significance for understanding the effect of infection episodes amongst people with type 1 diabetes, and the potential of a personalized health model in outbreak detection settings. The added benefit of the personalized health model concept introduced in this dissertation lies in its usefulness beyond the surveillance purpose, i.e. to devise decision support tools and learning platforms for the patient to manage infection-induced crises

Biological investigation and predictive modelling of foaming in anaerobic digester

Anaerobic digestion (AD) of waste has been identified as a leading technology for greener renewable energy generation as an alternative to fossil fuel. AD will reduce waste through biochemical processes, converting it to biogas which could be used as a source of renewable energy and the residue bio-solids utilised in enriching the soil. A problem with AD though is with its foaming and the associated biogas loss. Tackling this problem effectively requires identifying and effectively controlling factors that trigger and promote foaming. In this research, laboratory experiments were initially carried out to differentiate foaming causal and exacerbating factors. Then the impact of the identified causal factors (organic loading rate-OLR and volatile fatty acid-VFA) on foaming occurrence were monitored and recorded. Further analysis of foaming and nonfoaming sludge samples by metabolomics techniques confirmed that the OLR and VFA are the prime causes of foaming occurrence in AD. In addition, the metagenomics analysis showed that the phylum bacteroidetes and proteobacteria were found to be predominant with a higher relative abundance of 30% and 29% respectively while the phylum actinobacteria representing the most prominent filamentous foam causing bacteria such as Norcadia amarae and Microthrix Parvicella had a very low and consistent relative abundance of 0.9% indicating that the foaming occurrence in the AD studied was not triggered by the presence of filamentous bacteria. Consequently, data driven models to predict foam formation were developed based on experimental data with inputs (OLR and VFA in the feed) and output (foaming occurrence). The models were extensively validated and assessed based on the mean squared error (MSE), root mean squared error (RMSE), R2 and mean absolute error (MAE). Levenberg Marquadt neural network model proved to be the best model for foaming prediction in AD, with RMSE = 5.49, MSE = 30.19 and R2 = 0.9435. The significance of this study is the development of a parsimonious and effective modelling tool that enable AD operators to proactively avert foaming occurrence, as the two model input variables (OLR and VFA) can be easily adjustable through simple programmable logic controller

Network Pharmacology Approaches for Understanding Traditional Chinese Medicine

Traditional Chinese medicine (TCM) has obvious efficacy on disease treatments and is a valuable source for novel drug discovery. However, the underlying mechanism of the pharmacological effects of TCM remains unknown because TCM is a complex system with multiple herbs and ingredients coming together as a prescription. Therefore, it is urgent to apply computational tools to TCM to understand the underlying mechanism of TCM theories at the molecular level and use advanced network algorithms to explore potential effective ingredients and illustrate the principles of TCM in system biological aspects. In this thesis, we aim to understand the underlying mechanism of actions in complex TCM systems at the molecular level by bioinformatics and computational tools. In study Ⅰ, a machine learning framework was developed to predict the meridians of the herbs and ingredients. Finally, we achieved high accuracy of the meridians prediction for herbs and ingredients, suggesting an association between meridians and the molecular features of ingredients and herbs, especially the most important features for machine learning models. Secondly, we proposed a novel network approach to study the TCM formulae by quantifying the degree of interactions of pairwise herb pairs in study Ⅱ using five network distance methods, including the closest, shortest, central, kernel, as well as separation. We demonstrated that the distance of top herb pairs is shorter than that of random herb pairs, suggesting a strong interaction in the human interactome. In addition, center methods at the ingredient level outperformed the other methods. It hints to us that the central ingredients play an important role in the herbs. Thirdly, we explored the associations between herbs or ingredients and their important biological characteristics in study III, such as properties, meridians, structures, or targets via clusters from community analysis of the multipartite network. We found that herbal medicines among the same clusters tend to be more similar in the properties, meridians. Similarly, ingredients from the same cluster are more similar in structure and protein target. In summary, this thesis intends to build a bridge between the TCM system and modern medicinal systems using computational tools, including the machine learning model for meridian theory, network modelling for TCM formulae, as well as multipartite network analysis for herbal medicines and their ingredients. We demonstrated that applying novel computational approaches on the integrated high-throughput omics would provide insights for TCM and accelerate the novel drug discovery as well as repurposing from TCM.Perinteinen kiinalainen lääketiede (TCM) on ilmeinen tehokkuus taudin hoidoissa ja on arvokas lähde uuden lääkkeen löytämiseen. TCM: n farmakologisten vaikutusten taustalla oleva mekanismi pysyy kuitenkin tuntemattomassa, koska TCM on monimutkainen järjestelmä, jossa on useita yrttejä ja ainesosia, jotka tulevat yhteen reseptilääkkeeksi. Siksi on kiireellistä soveltaa Laskennallisia työkaluja TCM: lle ymmärtämään TCM-teorioiden taustalla oleva mekanismi molekyylitasolla ja käyttävät kehittyneitä verkkoalgoritmeja tutkimaan mahdollisia tehokkaita ainesosia ja havainnollistavat TCM: n periaatteita järjestelmän biologisissa näkökohdissa. Tässä opinnäytetyössä pyrimme ymmärtämään monimutkaisten TCM-järjestelmien toimintamekanismia molekyylitasolla bioinformaattilla ja laskennallisilla työkaluilla. Tutkimuksessa kehitettiin koneen oppimiskehystä yrttien ja ainesosien meridialaisista. Lopuksi saavutimme korkean tarkkuuden meridiaaneista yrtteistä ja ainesosista, mikä viittaa meridiaaneihin ja ainesosien ja yrtteihin liittyvien molekyylipiirin välillä, erityisesti koneen oppimismalleihin tärkeimmät ominaisuudet. Toiseksi ehdoimme uuden verkon lähestymistavan TCM-kaavojen tutkimiseksi kvantitoimisella vuorovaikutteisten yrttiparien vuorovaikutuksen tutkimuksessa ⅱ käyttämällä viisi verkkoetäisyyttä, mukaan lukien lähin, lyhyt, keskus, ydin sekä erottaminen. Osoitimme, että ylä-yrttiparien etäisyys on lyhyempi kuin satunnaisten yrttiparien, mikä viittaa voimakkaaseen vuorovaikutukseen ihmisellä vuorovaikutteisesti. Lisäksi Center-menetelmät ainesosan tasolla ylittivät muut menetelmät. Se vihjeitä meille, että keskeiset ainesosat ovat tärkeässä asemassa yrtteissä. Kolmanneksi tutkimme yrttien tai ainesosien välisiä yhdistyksiä ja niiden tärkeitä biologisia ominaisuuksia tutkimuksessa III, kuten ominaisuudet, meridiaanit, rakenteet tai tavoitteet klustereiden kautta moniparite-verkoston yhteisön analyysistä. Löysimme, että kasviperäiset lääkkeet samoilla klusterien keskuudessa ovat yleensä samankaltaisia ominaisuuksissa, meridiaaneissa. Samoin saman klusterin ainesosat ovat samankaltaisempia rakenteissa ja proteiinin tavoitteessa. Yhteenvetona tämä opinnäytetyö aikoo rakentaa silta TCM-järjestelmän ja nykyaikaisten lääkevalmisteiden välillä laskentatyökaluilla, mukaan lukien Meridian-teorian koneen oppimismalli, TCM-kaavojen verkkomallinnus sekä kasviperäiset lääkkeet ja niiden ainesosat Osoitimme, että uusien laskennallisten lähestymistapojen soveltaminen integroidulle korkean suorituskyvyttömiehille tarjosivat TCM: n näkemyksiä ja nopeuttaisivat romaanin huumeiden löytöä sekä toistuvat TCM: stä

Pharmacovigilance Decision Support : The value of Disproportionality Analysis Signal Detection Methods, the development and testing of Covariability Techniques, and the importance of Ontology

The cost of adverse drug reactions to society in the form of deaths, chronic illness, foetal malformation, and many other effects is quite significant. For example, in the United States of America, adverse reactions to prescribed drugs is around the fourth leading cause of death. The reporting of adverse drug reactions is spontaneous and voluntary in Australia. Many methods that have been used for the analysis of adverse drug reaction data, mostly using a statistical approach as a basis for clinical analysis in drug safety surveillance decision support. This thesis examines new approaches that may be used in the analysis of drug safety data. These methods differ significantly from the statistical methods in that they utilize co variability methods of association to define drug-reaction relationships. Co variability algorithms were developed in collaboration with Musa Mammadov to discover drugs associated with adverse reactions and possible drug-drug interactions. This method uses the system organ class (SOC) classification in the Australian Adverse Drug Reaction Advisory Committee (ADRAC) data to stratify reactions. The text categorization algorithm BoosTexter was found to work with the same drug safety data and its performance and modus operandi was compared to our algorithms. These alternative methods were compared to a standard disproportionality analysis methods for signal detection in drug safety data including the Bayesean mulit-item gamma Poisson shrinker (MGPS), which was found to have a problem with similar reaction terms in a report and innocent by-stander drugs. A classification of drug terms was made using the anatomical-therapeutic-chemical classification (ATC) codes. This reduced the number of drug variables from 5081 drug terms to 14 main drug classes. The ATC classification is structured into a hierarchy of five levels. Exploitation of the ATC hierarchy allows the drug safety data to be stratified in such a way as to make them accessible to powerful existing tools. A data mining method that uses association rules, which groups them on the basis of content, was used as a basis for applying the ATC and SOC ontologies to ADRAC data. This allows different views of these associations (even very rare ones). A signal detection method was developed using these association rules, which also incorporates critical reaction terms.Doctor of Philosoph

Clinical Studies, Big Data, and Artificial Intelligence in Nephrology and Transplantation

In recent years, artificial intelligence has increasingly been playing an essential role in diverse areas in medicine, assisting clinicians in patient management. In nephrology and transplantation, artificial intelligence can be utilized to enhance clinical care, such as through hemodialysis prescriptions and the follow-up of kidney transplant patients. Furthermore, there are rapidly expanding applications and validations of comprehensive, computerized medical records and related databases, including national registries, health insurance, and drug prescriptions. For this Special Issue, we made a call to action to stimulate researchers and clinicians to submit their invaluable works and present, here, a collection of articles covering original clinical research (single- or multi-center), database studies from registries, meta-analyses, and artificial intelligence research in nephrology including acute kidney injury, electrolytes and acid–base, chronic kidney disease, glomerular disease, dialysis, and transplantation that will provide additional knowledge and skills in the field of nephrology and transplantation toward improving patient outcomes

Modelling activated sludge wastewater treatment plants using artificial intelligence techniques (fuzzy logic and neural networks)

Activated sludge process (ASP) is the most commonly used biological wastewater treatment system. Mathematical modelling of this process is important for improving its treatment efficiency and thus the quality of the effluent released into the receiving water body. This is because the models can help the operator to predict the performance of the plant in order to take cost-effective and timely remedial actions that would ensure consistent treatment efficiency and meeting discharge consents. However, due to the highly complex and non-linear characteristics of this biological system, traditional mathematical modelling of this treatment process has remained a challenge. This thesis presents the applications of Artificial Intelligence (AI) techniques for modelling the ASP. These include the Kohonen Self Organising Map (KSOM), backpropagation artificial neural networks (BPANN), and adaptive network based fuzzy inference system (ANFIS). A comparison between these techniques has been made and the possibility of the hybrids between them was also investigated and tested. The study demonstrated that AI techniques offer viable, flexible and effective modelling methodology alternative for the activated sludge system. The KSOM was found to be an attractive tool for data preparation because it can easily accommodate missing data and outliers and because of its power in extracting salient features from raw data. As a consequence of the latter, the KSOM offers an excellent tool for the visualisation of high dimensional data. In addition, the KSOM was used to develop a software sensor to predict biological oxygen demand. This soft-sensor represents a significant advance in real-time BOD operational control by offering a very fast estimation of this important wastewater parameter when compared to the traditional 5-days bio-essay BOD test procedure. Furthermore, hybrids of KSOM-ANN and KSOM-ANFIS were shown to result much more improved model performance than using the respective modelling paradigms on their own.Damascus Universit