Clinical risk modelling with machine learning: adverse outcomes of pregnancy

As a complex biological process, there are various health issues that are related to pregnancy. Prenatal care, a type of preventative healthcare at different points in gestation is comprised of management, treatment, and mitigation of such issues. This also includes risk prediction for adverse pregnancy outcomes, where probabilistic modelling is used to calculate individual’s risk at the early stages of pregnancy. This type of modelling can have a definite clinical scope such as in prenatal screening, and an educational aim where awareness of a healthy lifestyle is promoted, such as in health education. Currently, the most used models are based on traditional statistical approaches, as they provide sufficient predictive power and are easily interpreted by clinicians. Machine learning, a subfield of data science, contains methods for building probabilistic models with multidimensional data. Compared to existing prediction models related to prenatal care, machine learning models can provide better results by fitting more intricate nonlinear decision boundary areas, improve data-driven model fitting by generating synthetic data, and by providing more automation for routine model adjustment processes. This thesis presents the evaluation of machine learning methods to prenatal screening and health education prediction problems, along with novel methods for generating synthetic rare disorder data to be used for modelling, and an adaptive system for continuously adjusting a prediction model to the changing patient population. This way the thesis addresses all the four main entities related to predicting adverse outcomes of pregnancy: the mother or patient, the clinician, the screening laboratory and the developer or manufacturer of screening materials and systems.Kliinisen riskin mallinnus koneoppimismenetelmin: raskaudelle haitalliset lopputulemat Raskaus on kompleksinen biologinen prosessi, jonka etenemiseen liittyy useita terveysongelmia. Äitiyshoito voidaan kuvata ennalta ehkäiseväksi terveydenhuolloksi, jossa pyritään käsittelemään, hoitamaan ja lievittämään kyseisiä ongelmia. Tähän hoitoon sisältyy myös raskauden haitallisten lopputulemien riskilaskenta, missä probabilistista mallinnusta hyödynnetään määrittämään yksilön riski raskauden varhaisissa vaiheissa. Tällä mallinnuksella voi olla selkeä kliininen tarkoitus kuten prenataaliseulonta, tai terveyssivistyksellinen tarkoitus missä odottavalle äidille esitellään raskauden kannalta terveellisiä elämäntapoja. Tällä hetkellä eniten käytössä olevat ennustemallit perustuvat perinteiseen tilastolliseen mallinnukseen, sille ne tarjoavat riittävän ennustetehokkuuden ja ovat helposti tulkittavissa. Koneoppiminen on datatieteen osa-alue, joka pitää sisällään menetelmiä millä voidaan mallintaa moniulotteista dataa ennustekäyttöön. Verrattuna olemassa oleviin äitiyshoidon ennustemalleihin, koneoppiminen mahdollistaa parempien ennustetulosten tuottamisen sovittamalla hienojakoisempia epälineaarisia päätösalueita, tehostamalla datakeskeisten mallien sovitusta luomalla synteettisiä havaintoja ja tarjoamalla enemmän automaatiota rutiininomaiseen mallien hienosäätöön. Tämä väitös esittelee koneoppimismenetelmien evaluaation prenataaliseulonta-ja terveyssivistysongelmiin, ja uusia menetelmiä harvinaisten sairauksien datan luomiseen mallinnustarkoituksiin ja jatkuvan ennustemallin hienosäätämisen järjestelmän muuttuvia potilaspopulaatiota varten. Näin väitös käy läpi kaikki neljä asianomaista jotka liittyvät haitallisten lopputulemien ennustamiseen: odottava äiti eli potilas, kliinikko, seulontalaboratorio ja seulonnassa käytettävien materiaalien ja järjestelmien kehittäjä tai valmistaja

Appraising self-advocacy in the lives of people with learning difficulties.

This thesis presents an appraisal of self-advocacy in the lives of people with learning difficulties ('self-advocates'). The study consists of thesis (volume I) and appendix (volume II). The thesis attempts to answer three questions: 1. What is the nature of the contemporary self-advocacy movement? 2. How do self-advocacy groups impact upon the lives of people with learning difficulties? 3. How do self-advocacy groups work? The first section of the thesis reviews the literature on self-advocacy of people with learning difficulties, introduces an inclusive social model of disability (the guiding theoretical perspective of this appraisal) and critically outlines the methods employed in this study. The next three sections present findings from the empirical work: • Section 2 - The nature of the contemporary self-advocacy movement - reports on the findings from a postal survey of 134 self-advocacy groups, highlighting the complexity within the movement, overlap of group types and variety of group affiliations. • Section 3 - Living self-advocacy - presents the life stories of five self-advocates who have had long-term involvement with self advocacy groups. Broad themes are drawn out from the stories, including life before self-advocacy groups, coming out as a self advocate and expert advice. Attention is also paid to the writing of life stories in collaborative narrative inquiry. • Section 4 - Self-advocacy in action - delves into the dynamics of four self-advocacy groups as gleaned through an ethnographic study. Each group is described and appraised, the self-advocacy literature is revisited in light of the observed workings of groups and the notion of support is considered with reference to models of disability. Finally, the doing of ethnography is explored with reference to subjectivity, method and analysis. The final section of the thesis revisits self-advocacy in light of the empirical findings. It is concluded that even when self-advocates are disabled by excluding barriers and stifled by the 'support' of others and the affiliations of their self-advocacy groups, their resilience shines through

Attitudes of disabled people toward other disabled people and impairment groups

This research set-out to: a) investigate attitudes of disabled people (adults) toward other disabled people; and, b) attitudes of disabled people toward different impairment groups. Comparative data from a non-disabled sample was also collected. Two new attitude rating scales were developed for this research: the General Attitude Scale Toward Disabled People (GASTDP) and the Attitude Toward Impairment Scale (A TIS). Both scales achieved acceptable levels of internal and external reliability. Positive attitudes toward disabled people were found from both the disabled (M = 41.08; n = 193) and non-disabled samples (M = 39.29; n = 120). However, a hierarchy of impairment also appears to exist, with the disabled sample producing a rank ordering of most accepted to least of Deaf, Arthritis, Epilepsy, Cerebral Palsy, HIV/AIDS, Down's Syndrome and Schizophrenia. The nondisabled sample rank ordering was the same for five of the seven impairment groups, with only Cerebral Palsy and HIV / AIDS being placed in reverse order. The GASTDP contains two sub-scales (Subtle and Blatant Prejudice subscales). Statistically significant results between the two sub-scales were found for both the disabled and non-disabled samples, suggesting people tend to hold subtle forms of prejudice toward disabled people. The discussion therefore utilises the term aversive disablism, based on aversive racism. This theory argues that whilst people may be reluctant to express negative attitudes toward disabled people, they may also support policies that are disablist, i.e. segregated housing. The contact hypothesis, whereby contact with members of a minority group influence attitudes, was not supported by the data. This thesis recommends further research into subtle forms of prejudice toward disabled people from an in-group perspective and attitudes toward different impairment groups

Civil transporter conceptual design studies and tradeoff methodologies using a Matlab computational environment

The thesis consists of two parts. Part 1 covers basic philosophy and theory and Part 2 with their practical application in a series of investigations conducted with omputerised modules. Part 2 is rounded off with a chapter dedicated to critical discussions of the investigations and culminates with a conclusions chapter. The first chapter of Part 1 describes twin aims of the thesis the first being the study and development of tradeoff methodology with particular emphasis on its use during the conceptual phase of a modern jet transporter, and the second the complementary development of a generalised methodology for conceptual design based on relatively simple models and facilitated by the establishment of a PC based computational environment. The aims thus stated are complemented by listed primary and secondary objectives. The second chapter is a review of literature which presents critical surveys and appraisals of all the areas which were the subject of investigative reading. The review is an essential preliminary to Chapter 3 inasmuch as the experience gained conditioned the development of the working philosophy and computer models which are described therein. This major chapter is structured as a sequence of perspectives commencing with a more detailed exposition of the thesis objectives, goes on to develop the working philosophy and then addresses the theoretical basis of the computer modules which support the implementation of the second of the two stated aims. All the necessary equations are described at this stage. The modules devised serve two functions namely Parametric and Decision Analysis. The first is supported by Base, Optimising and Costing modules and the second by a Compromiser and Selector Module. The Compromiser module to some extent complements the Optimiser Module. Part 2 is mainly concerned with the application of the modules introduced in Part 1 and largely devolves on how these are used within the Matlab software environment. The first chapter of Part 2 is especially important as it describes the way the input data and Matlab syntaxes are prepared. It is important to realise that the use ofMatlab software requires a highly structured discipline and considerable experience is required for its effective application. The next chapter describes a series of investigations devoted to parametric analysis using the Base and Optimiser modules and presents the results in graphs and charts. The processing of the results is an important feature of the analysis. The Compromiser and Selector modules are exercised with practical applications relating to goal attainment and aircraft selection. The penultimate chapter presents critical discussions relating to (a) the results obtained by the investigations and (b) to the analytical approaches taken. The final chapter specifies conclusions relating to the fulfilment of the aims and objectives~ innovation and originality and recommendations for future research. Some of the research undertaken was eventually judged to be peripheral to the main thrust of the thesis. However the information it provided was judged to be sufficiently useful to be worth preserving in supporting appendices

Non-invasive prenatal diagnosis and testing: perspectives on the emergence and translation of a new prenatal testing technology

This thesis presents findings from a qualitative study of the emergence and early clinical translation of non-invasive prenatal diagnosis (NIPD) in the UK. Drawing from interviews with a range of experts and users I track the enrolment and translation of this new prenatal testing technology across a variety of clinical and social spaces. I show how encounters with NIPD prompt deep critical examination of the moral, social and political implications - not only of the technology - but of the established clinical practices (routine and specialised prenatal testing) and specific policy contexts (prenatal screening programmes) within which NIPD has begun to sediment. I explore how, as NIPD advances at a rapid pace and emerges within a culturally and politically complex context, the technology both aligns with and disrupts routine practices of prenatal screening and diagnosis. I show how, as the technology divides into two major strands - NIPD and NIPT - at an early stage of development, and before becoming naturalised/normalised within the clinic, scientists, clinicians and policy makers attempt to pin down, define and ‘fix’ the technology, drawing upon and engaging in substantive practices of division, categorisation and classification. I explore ambiguities present within such accounts, highlighting dissenting voices and moments of problematisation, and following this, I show how the ‘troubling’ of boundaries prompts much examination of ethical and social concerns. As a location within which interviewees explored more contentious issues, I show how abortion emerged as central to the discussion of NIPD. I proceed to show how institutionalised, professionalised bioethical debate dominates mainstream discourse, and I explain how a particular construction of the informed, individual choice-maker is mobilised in order to locate moral and political responsibility for testing in the hands of individuals, and to distance political/organisational structures from entanglement with problematic concerns. I explore how clinicians and patients respond to this positioning in multiple ways, both assimilating and questioning the mainstream discourse of ‘informed choice’. In conclusion, I highlight the broader (bio)political aspects of NIPD’s emergence and translation within prenatal screening and diagnosis