A CASE-BASED REASONING SYSTEM FOR THE DIAGNOSIS OF INDIVIDUAL SENSITIVITY TO STRESS IN PSYCHOPHYSIOLOGY

Abstract Stress is an increasing problem in our present world. Especially negative stress could cause serious health problems if it remains undiagnosed/misdiagnosed and untreated. In stress medicine, clinicians' measure blood pressure, ECG, finger temperature and breathing rate during a number of exercises to diagnose stressrelated disorders. One of the physiological parameters for quantifying stress levels is the finger temperature measurement which helps the clinicians in diagnosis and treatment of stress. However, in practice, it is difficult and tedious for a clinician to understand, interpret and analyze complex, lengthy sequential sensor signals. There are only few experts who are able to diagnose and predict stress-related problems. A system that can help the clinician in diagnosing stress is important, but the large individual variations make it difficult to build such a system. This research work has investigated several artificial Intelligence techniques for the purpose of developing an intelligent, integrated sensor system for establishing diagnosis and treatment plan in the psychophysiological domain. To diagnose individual sensitivity to stress, case-based reasoning is applied as a core technique to facilitate experience reuse by retrieving previous similar cases. Furthermore, fuzzy techniques are also employed and incorporated into the case-based reasoning system to handle vagueness, uncertainty inherently existing in clinicians reasoning process. The validation of the approach is based on close collaboration with experts and measurements from twenty four persons used as reference. 39 time series from these 24 persons have been used to evaluate the approach (in terms of the matching algorithms) and an expert has ranked and estimated the similarity. The result shows that the system reaches a level of performance close to an expert. The proposed system could be used as an expert for a less experienced clinician or as a second option for an experienced clinician to their decision making process in stress diagnosis. Sammanfattning Den ökande stressnivån i vårt samhälle med allt högre krav och högt tempo har ett högt pris. Stressrelaterade problem och sjukdom är en stor samhällskostnad och speciellt om negativ stress förblir oupptäckt, eller ej korrekt identifierad/diagnostiserad och obehandlad under en längre tid kan den få alvarliga hälsoeffekter för individen vilket kan leda till långvarig sjukskrivning. Inom stressmedicinen mäter kliniker blodtryck, EKG, fingertemperatur och andning under olika situationer för att diagnostisera stress. Stressdiagnos baserat fingertemperaturen (FT) är något som en skicklig klinker kan utföra vilket stämmer med forskningen inom klinisk psykofysiologi. Emellertid i praktiken är det mycket svårt, och mödosamt för att en kliniker att i detalj följa och analysera långa serier av mätvärden och det finns endast mycket få experter som är kompetent att diagnostisera och/eller förutsäga stressproblem. Därför är ett system, som kan hjälpa kliniker i diagnostisering av stress, viktig. Men de stora individvariationerna och bristen av precisa diagnosregler gör det svårt att använda ett datorbaserat system. Detta forskningsarbete har tittat på flera tekniker och metoder inom artificiell intelligens för att hitta en väg fram till ett intelligent sensorbaserat system för diagnos och utformning av behandlingsplaner inom stressområdet. För att diagnostisera individuell stress har fallbaserat resonerande visat sig framgångsrikt, en teknik som gör det möjligt att återanvända erfarenhet, förklara beslut, genom att hämta tidigare liknande fingertemperaturprofilerar. Vidare används "fuzzy logic", luddig logik så att systemet kan hantera de inneboende vagheter i domänen. Metoder och algoritmer har utvecklats för detta. Valideringen av ansatsen baseras på nära samarbete med experter och mätningar från tjugofyra användare. Trettionio tidserier från dessa 24 personer har varit basen för utvärderingen av ansatsen, och en erfaren kliniker har klassificerat alla fall och systemet har visat sig producera resultat nära en expert. Det föreslagna systemet kan användas som ett referens för en mindre erfaren kliniker eller som ett "second opinion" för en erfaren kliniker i deras beslutsprocess. Dessutom har finger temperatur visat sig passa bra för användning i hemmet vid träning eller kontroll vilket blir möjligt med ett datorbaserat stressklassificeringssystem på exempelvis en PC med en USB fingertemperaturmätare. vii Acknowledgemen

The ‘Meanings’ and ‘Enactments’ of Science and Technology: ANT-Mobilities’ Analysis of Two Cases

In this work I study two cases involving practices of science and technology in the backdrop of related and recent curricular reforms in both settings. The first case study is based on the 2005 South Asian earthquake in Muzaffarabad, Pakistan which led to massive losses including large scale injuries and disabilities. This led to reforms at many levels ranging from disaster management to action plans on disability, including educational reforms in rehabilitation sciences. Local efforts to deal with this disaster led to innovative approaches such as the formation of a Community Based Rehabilitation (CBR) model by a local NGO, which I study in detail. The second case study is based on the recent reform of science and technology curriculum in Ontario, which is related to the release of the 2007 Intergovernmental Panel for Climate Change (IPCC) reports. With climate change science driving this reform with curricular demands for students to learn ‘what scientists do’, my second case study details the formation of the Canadian CloudSat CALIPSO Validation Project (C3VP) and scientific practices which depict cutting edge science related to climate change. Towards contending with the complexity inherent in these cases, I have developed a hybrid framework which is based on Actor-Network Theory (ANT) and the mobilities paradigm while drawing on some aspects of the Annales school of historians. The resulting historical sociology or historiography depicts how these various networks were formed via mobilities of various actor-networks and vice versa. The practices involved in both cases evolved over time and required innovation in times of crises and challenges, and are far more than simple applications of method as required by biomedical and positivist representations of science inherent in both educational reforms. Non-human agency in the form of crisis and disaster also emerges as a key reason for the formation of these networks. Drawing from both cases, I introduce the concept of “transectionalities” as a metaphor which represent configurations of actor-networks in science and technology geared towards dealing with crisis and disaster scenarios. Based on these findings, I also extend the idea of “multiple ontologies” by Mol (2002) to “Epistemic-Ontologic-Techne-” configurations which is sensitive to considerations of time. Moreover, I also find that mathematics is a key mobilizing actor and material semiotic which mediates communication between humans and non-humans and term these dynamics as “mathematical mobilities.” Based on case study one, I also suggest the notion of “affective care” in clinical reasoning, which is based on enhancing the beneficial effect of human to human relationships in these engagements

A probabilistic examplar based model

A central problem in case based reasoning (CBR) is how to store and retrievecases. One approach to this problem is to use exemplar based models, where onlythe prototypical cases are stored. However, the development of an exemplar basedmodel (EBM) requires the solution of several problems: (i) how can a EBM berepresented? (ii) given a new case, how can a suitable exemplar be retrieved? (iii)what makes a good exemplar? (iv) how can an EBM be learned incrementally?This thesis develops a new model, called a probabilistic exemplar based model,that addresses these research questions. The model utilizes Bayesian networksto develop a suitable representation and uses probability theory to develop thefoundations of the developed model. A probability propagation method is usedto retrieve exemplars when a new case is presented and for assessing the prototypicalityof an exemplar.The model learns incrementally by revising the exemplars retained and byupdating the conditional probabilities required by the Bayesian network. Theproblem of ignorance, encountered when only a few cases have been observed,is tackled by introducing the concept of a virtual exemplar to represent all theunseen cases.The model is implemented in C and evaluated on three datasets. It is alsocontrasted with related work in CBR and machine learning (ML)

A novel case-based reasoning approach to radiotherapy dose planning

In this thesis, novel Case-Based Reasoning (CBR) methods were developed to be included in CBRDP (Case-Based Reasoning Dose Planner) -an adaptive decision support system for radiotherapy dose planning. CBR is an artificial intelligence methodology which solves new problems by retrieving solutions to previously solved similar problems stored in a case base. The focus of this research is on dose planning for prostate cancer patients. The records of patients successfully treated in the Nottingham University Hospitals NHS Trust, City Hospital Campus, UK, were stored in a case base and were exploited using case-based reasoning for future decision making. After each successful run of the system, a group based Simulated Annealing (SA) algorithm automatically searches for an optimal/near optimal combination of feature weights to be used in the future retrieval process of CBR. A number of research issues associated with the prostate cancer dose planning problem and the use of CBR are addressed including: (a) trade-off between the benefit of delivering a higher dose of radiation to cancer cells and the risk to damage surrounding organs, (b) deciding when and how much to violate the limitations of dose limits imposed to surrounding organs, (c) fusion of knowledge and experience gained over time in treating patients similar to the new one, (d) incorporation of the 5 years Progression Free Probability and success rate in the decision making process and (e) hybridisation of CBR with a novel group based simulated annealing algorithm to update knowledge/experience gained in treating patients over time. The efficiency of the proposed system was validated using real data sets collected from the Nottingham University Hospitals. Experiments based on a leave-one-out strategy demonstrated that for most of the patients, the dose plans generated by our approach are coherent with the dose plans prescribed by an experienced oncologist or even better. This system may play a vital role to assist the oncologist in making a better decision in less time; it incorporates the success rate of previously treated similar patients in the dose planning for a new patient and it can also be used in teaching and training processes. In addition, the developed method is generic in nature and can be used to solve similar non-linear real world complex problems

Clinical evaluation of a novel adaptive bolus calculator and safety system in Type 1 diabetes

Bolus calculators are considered state-of-the-art for insulin dosing decision support for people with Type 1 diabetes (T1D). However, they all lack the ability to automatically adapt in real-time to respond to an individual’s needs or changes in insulin sensitivity. A novel insulin recommender system based on artificial intelligence has been developed to provide personalised bolus advice, namely the Patient Empowerment through Predictive Personalised Decision Support (PEPPER) system. Besides adaptive bolus advice, the decision support system is coupled with a safety system which includes alarms, predictive glucose alerts, predictive low glucose suspend for insulin pump users, personalised carbohydrate recommendations and dynamic bolus insulin constraint. This thesis outlines the clinical evaluation of the PEPPER system in adults with T1D on multiple daily injections (MDI) and insulin pump therapy. The hypothesis was that the PEPPER system is safe, feasible and effective for use in people with TID using MDI or pump therapy. Safety and feasibility of the safety system was initially evaluated in the first phase, with the second phase evaluating feasibility of the complete system (safety system and adaptive bolus advisor). Finally, the whole system was clinically evaluated in a randomised crossover trial with 58 participants. No significant differences were observed for percentage times in range between the PEPPER and Control groups. For quality of life, participants reported higher perceived hypoglycaemia with the PEPPER system despite no objective difference in time spent in hypoglycaemia. Overall, the studies demonstrated that the PEPPER system is safe and feasible for use when compared to conventional therapy (continuous glucose monitoring and standard bolus calculator). Further studies are required to confirm overall effectiveness.Open Acces

Process engineering of liver cells for drug testing applications

Dissertação para obtenção do Grau de Doutor em BioengenhariaThe primary culture of human hepatocytes is a requirement in drug development tests. This application is currently hampered by two problems: the limited proliferation of the hepatocytes and the rapid loss of liver-specific phenotype of these cells, when cultured in vitro. This thesis aimed at minimizing this latter issue by cultivating hepatocytes, as spheroids, in fully controlled bioreactors. The state of the art of the primary cultures of hepatocytes is reviewed in Chapter 1, after a brief introduction to the liver physiology the drug development process. The improvement of the bioreactor cultures of hepatocyte spheroids was initially done using freshly isolated rat hepatocytes; the effects of alginate microencapsulation, perfusion culture and their synergy on the maintenance of the hepatocyte spheroids liver-specific phenotype were assessed in Chapters 2 and 3; it was concluded that the perfusion culture and alginateencapsulation had a positive synergic effect on such hepatic phenotype. The perfusion bioreactor developed in Chapter 3 was used in Chapter 4 for the extended culture of freshly isolated human hepatocytes, as spheroids, from three different donors. These cultures responded to repeated dose drug treatments as expected from mature and differentiated hepatocytes, in up to 4 weeks culture time. In Chapter 5, human embryonic stem cell-derived hepatic progenitors were cultured as spheroids and further differentiated into hepatocyte-like cells; the differential expression of hepatic genes between this spheroid population and a monolayer differentiated hepatocyte-like cell population showed a more efficient differentiation under spheroid culture. The bioengineering improvements of this thesis, as well as the future work, were discussed in Chapter 6. This thesis has led to the establishment and validation of primary cultures of hepatocyte spheroids, in perfusion bioreactors, which can be used for long-term, repeated dose tests in drug development

A novel case-based reasoning approach to radiotherapy dose planning

In this thesis, novel Case-Based Reasoning (CBR) methods were developed to be included in CBRDP (Case-Based Reasoning Dose Planner) -an adaptive decision support system for radiotherapy dose planning. CBR is an artificial intelligence methodology which solves new problems by retrieving solutions to previously solved similar problems stored in a case base. The focus of this research is on dose planning for prostate cancer patients. The records of patients successfully treated in the Nottingham University Hospitals NHS Trust, City Hospital Campus, UK, were stored in a case base and were exploited using case-based reasoning for future decision making. After each successful run of the system, a group based Simulated Annealing (SA) algorithm automatically searches for an optimal/near optimal combination of feature weights to be used in the future retrieval process of CBR. A number of research issues associated with the prostate cancer dose planning problem and the use of CBR are addressed including: (a) trade-off between the benefit of delivering a higher dose of radiation to cancer cells and the risk to damage surrounding organs, (b) deciding when and how much to violate the limitations of dose limits imposed to surrounding organs, (c) fusion of knowledge and experience gained over time in treating patients similar to the new one, (d) incorporation of the 5 years Progression Free Probability and success rate in the decision making process and (e) hybridisation of CBR with a novel group based simulated annealing algorithm to update knowledge/experience gained in treating patients over time. The efficiency of the proposed system was validated using real data sets collected from the Nottingham University Hospitals. Experiments based on a leave-one-out strategy demonstrated that for most of the patients, the dose plans generated by our approach are coherent with the dose plans prescribed by an experienced oncologist or even better. This system may play a vital role to assist the oncologist in making a better decision in less time; it incorporates the success rate of previously treated similar patients in the dose planning for a new patient and it can also be used in teaching and training processes. In addition, the developed method is generic in nature and can be used to solve similar non-linear real world complex problems

Framing a Knowledge Base for a Legal Expert System Dealing with Indeterminate Concepts

Despite decades of development of formal tools for modelling legal knowledge and reasoning, the creation of a fully fledged legal decision support system remains challenging. Among those challenges, such system requires an enormous amount of commonsense knowledge to derive legal expertise. This paper describes the development of a negotiation decision support system (the Parenting Plan Support System or PPSS) to support parents in drafting an agreement (the parenting plan) for the exercise of parental custody of minor children after a divorce is granted. The main objective here is to discuss problems of framing an intuitively appealing and computationally efficient knowledge base that can adequately represent the indeterminate legal concept of the well-being of the child in the context of continental legal culture and of Polish law in particular. In addition to commonsense reasoning, interpretation of such a concept demands both legal expertise and significant professional knowledge from other domains