Dissertations / Theses on the topic 'Causes and theories of causations'

Reprints of the author's previously published articles included as an appendix. Bibliography: leaves 165-188. "This thesis describes a series of experiments that aimed to investigate the effects of folic acid deficiency and defects in folate metabolism on chromosome damage rates in human lymphocytes. The accumulation of chromosome damage over time is an important issue because it is thought to contribute to the mechanism of ageing and the aetiology of diseases of age such as cancer and Alzheimer's disease."

Injury now surpasses disease as the leading global cause of premature death and disability, claiming over 5.8 millions lives each year. However, unlike disease, which has been subjected to a rigorous epidemiologic approach, the field of injury prevention and control has been a relative newcomer to scientific investigation. With the distribution of injury now well described (i.e. ???who???, ???what???, ???where??? and ???when???), the underlying hypothesis is that progress in understanding ???how??? and ???why??? lies in classifying injury occurrences aetiologically. The advancement of a means of classifying injury aetiology has so far been inhibited by two related limitations: 1. Structural limitation: The absence of a cohesive and validated aetiological taxonomy for injury, and; 2. Methodological limitation: The need to manually classify large numbers of injury cases to determine aetiological patterns. This work is directed at overcoming these impediments to injury research. An aetiological taxonomy for injury was developed consistent with epidemiologic principles, along with clear conventions and a defined three-tier hierarchical structure. Validation testing revealed that the taxonomy could be applied with a high degree of accuracy (coder/gold standard agreement was 92.5-95.0%), and with high inter- and intra- coder reliability (93.0-96.3% and 93.5-96.3%). Practical application demonstrated the emergence of strong aetiological patterns which provided insight into causative sequences leading to injury, and led to the identification of effective control measures to reduce injury frequency and severity. However, limitations related to the inefficient and error-prone manual classification process (i.e. average 4.75 minute/case processing time and 5.0-7.5% error rate), revealed the need for an automated approach. To overcome these limitations, a knowledge acquisition (KA) software tool was developed, tested and applied, based on an expertsystems technique known as ripple down rules (RDR). It was found that the KA system was able acquire tacit knowledge from a human expert and apply learned rules to efficiently and accurately classify large numbers of injury cases. Ultimately, coding error rates dropped to 3.1%, which, along with an average 2.50 minute processing time, compared favourably with results from manual classification. As such, the developed taxonomy and KA tool offer significant advantages to injury researchers who have a need to deduce useful patterns from injury data and test hypotheses regarding causation and prevention.

The objectives of this study were to determine what the Tumbuka people of northern Malawi consider to be the most dangerous childhood diseases, to explore their perceptions about the aetiology, prevention and treatment of these diseases, and to determine how such perceptions have changed over the years. The study was done in Chisinde and surrounding villages in western Rumphi District, northern Malawi. Although a household questionnaire was used to collect some quantitative data, the major data collection methods comprised participant observation, in-depth interviews with mothers with children under five and old men and women, and key informant interviews with traditional healers, traditional birth attendants, village headmen, health surveillance assistants and clinical officers. Informants in this study mentioned chikhoso chamoto, diarrhoea, malaria, measles, and conjunctivitis as the most dangerous childhood diseases in the area. Old men and women added that in the past smallpox was also a dangerous disease that affected both children and adults. Apart from measles and smallpox, community-based health workers and those at the local health centre also mentioned the same list of diseases as the most dangerous diseases prevalent among under-five children. Though health workers and informants mentioned the same diseases, the informants' perspectives about the aetiology and prevention of these diseases and the way they sought treatment during childhood illness episodes, in some cases, differed significantly from those of biomedicine. For example, while health workers said that the signs and symptoms presented by a child suffering from "chikhoso chamoto" were those of either kwashiorkor or marasmus, both young and elderly informants said that a child could contract this illness through contact with a person who had been involved in sexual intercourse. Biomedically, diarrhoea is caused by the ingestion of pathogenic agents, which are transmitted through, among other factors, drinking contaminated water and eating contaminated foods. While young men and women subscribed to this biomedical view, at the same time, just like old men and women, they also believed that if a breastfeeding mother has sexual intercourse, sperms will contaminate her breast milk and, once a child feeds on this milk, he or she will develop diarrhoea. They, in addition, associated diarrhoea with the process of teething and other infections, such as malaria and measles. In malaria-endemic areas such as Malawi, the occurrence of convulsions, splenomegaly and anaemia in children under five may be biomedically attributed to malaria. However, most informants in this study perceived these conditions as separate disease entities caused by, among other factors, witchcraft and the infringement of Tumbuka taboos relating to food, sexual intercourse and funerals. Splenomegaly and convulsions were also perceived as hereditary diseases. Such Tumbuka perceptions about the aetiology of childhood diseases also influenced their ideas about prevention and the seeking of therapy during illness episodes. Apart from measles, other childhood vaccine-preventable diseases (i.e. tetanus, diphtheria, tuberculosis, pertussis and poliomyelitis) were not mentioned, presumably because they are no longer occurring on a significant scale, which is an indication of the success of vaccination programmes. This study reveals that there is no outright rejection of vaccination services in the study area. Some mothers, though, felt pressured to go for vaccination services as they believed that non-vaccinated children were refused biomedical treatment at the local health centres when they fell ill. While young women with children under five mentioned vaccination as a preventative measure against diseases such as measles, they also mentioned other indigenous forms of 'vaccination', which included the adherence to societal taboos, the wearing of amulets, the rubbing of protective medicines into incisions, isolation of children under five (e.g. a newly born child is kept in the house, amongst other things, to protect him or her against people who are ritually considered hot because of sexual intercourse) who are susceptible to disease or those posing a threat to cause disease in children under five. For example, since diarrhoea is perceived to be caused by, among other things, a child feeding on breast milk contaminated with sperms, informants said that there is a strong need for couples to observe postpartum sexual intercourse. A couple with newly delivered twins is isolated from the village because of the belief that children will swell if they came into contact with them. Local methods of disease prevention seem therefore to depend on what is perceived to be the cause of the illness and the decision to adopt specific preventive measures depends on, among other factors, the diagnosis of the cause and of who is vulnerable. The therapy-seeking process is a hierarchical movement within and between aetiologies; at the same time, it is not a random process, but an ordered process of choices in response to negative feedback, and subject to a number of factors, such as the aetiology of the disease, distance, social costs, cost of the therapeutic intervention, availability of medicines, etc. The movement between systems (i.e. from traditional medicine to biomedicine and vice-versa) during illness episodes depends on a number of factors, including previous experiences of significant others (i.e. those close to the patient), perceptions about the chances of getting healed, the decisions of the therapy management group, etc. For example, febrile illness in children under five may be treated using herbs or antipyretics bought from the local grocery shops. When the situation worsens (e.g. accompanied by convulsions), a herbalist will be consulted or the child may be taken to the local health centre. The local health centre refers such cases to the district hospital for treatment. Because of the rapidity with which the condition worsens, informants said that sometimes such children are believed to be bewitched, hence while biomedical treatment is sought, at the same time diviners are also consulted. The therapeutic strategies people resort to during illness episodes are appropriate rational decisions, based on prevailing circumstances, knowledge, resources and outcomes. Boundaries between the different therapeutic options are not rigid, as people move from one form of therapy to another and from one mode of classification to another. Lastly, perceptions about childhood diseases have changed over the years. Old men and women mostly attribute childhood illnesses to the infringement of taboos (e.g. on . sexual intercourse), witchcraft and other supernatural forces. While young men and women also subscribe to these perceptions, they have at the same time also appropriated the biomedical disease explanatory models. These biomedical models were learnt at school, acquired during health education sessions conducted by health workers in the communities as well as during under-five clinics, and health education programmes conducted on the national radio station. Younger people, more frequently than older people, thus move within and between aetiological models in the manner described above.

One of the most interesting developments in recent psychological theorising has been a growing appreciation of the need for a viable theory of mental causation. Hitherto, the prospects for reconciling what seems to be the uniquely rational character of human thought and action with the non-rational mechanistic workings of the natural world have appeared to be limited or even illusory, and the pursuit of reconciliation of this sort has therefore formerly been dismissed as being either impossible of completion or inappropriate for contemplation. Much of the scepticism concerning the role of causal processes in human thought and action was dispelled, however, by the philosopher Donald Davidson, who argues that not only is human action capable of being caused by the actor�s thoughts and desires, but that only when such action is so caused, can it be rational. Davidson�s proposal for the reconciliation of human rationality with causal necessitation is articulated in his theory of Anomalous Monism. According to this theory, there exists what may be termed an ontological-conceptual distinction between events themselves and the characters or properties that are attributed to events by human observers, and it is through recognition of this distinction that one discovers how mental events, that is, events that are amenable to description in the psychological vocabulary, are causally efficacious yet free from the constraints typically associated with the necessity and sufficiency of causal laws. Anomalous Monism, if it were workable, would therefore resolve the paradox according to which human mentality is at once integrated in, and yet unconstrained by, the mechanistic natural world, by demonstrating the compatibility of the facts of causation with the intuitions of folk psychology. However, close examination of Anomalous Monism reveals it to rely on logically flawed anti-realist principles concerning the characters of events, properties and causation. It follows from this that the theory itself must be rejected, but the task that it was devised to undertake, the formulation of a viable theory of mental causation, need not be similarly discarded. Rather, what remains is the challenge of delineating an alternative theory, one that withstands logical scrutiny whilst addressing what is characteristic of human mental processes, and thereby what is characteristic of mental causation. The theory of Direct Realism that is derived from the broader philosophical realism of John Anderson provides the materials for meeting this challenge. According to Direct Realism, mental phenomena are relational situations obtaining between certain organisms (including humans) and their environments. As such, mental phenomena are included in the range of phenomena occurring in the natural world and they are therefore subject to all of its ways of working, including its deterministic mechanisms. The particular challenge that a Direct Realist theory of mental causation faces, that of demonstrating that relational situations can be causal, is revealed upon examination of the character of causation to be unproblematic. Furthermore, the seeming incompatibility between human rationality and natural necessitation is resolved when it is acknowledged that, rather than be an inherent feature of thought and action, logical structure is a characteristic of the natural environment that organisms are at times sensitive to, as revealed by its effects on the characters of their thoughts and actions. Far from being remote or illusory, the prospects for reconciling human mentality with the causal mechanisms of the natural world are discovered in the present thesis to be favourable when a realist approach to the characters of both mental events and causation is adopted.

Thesis (Ph. D.)--University of Sydney, 2004.
Title from title screen (viewed 14 May 2008). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the School of Psychology, Faculty of Science. Includes bibliographical references. Also available in print form.

Although tuberculosis (TB) stigma has been widely reported in South Asia and elsewhere, few interventions have been introduced to reduce it. Whilst it is recognised that stigma interventions need to address the fundamental causes of stigma and that their design needs to be theory-driven, causal theories to explain TB stigma are lacking. In this thesis I present the development of causal theories to explain manifestations of TB stigma and identify theory-driven approaches to addressing TB stigma in South Asia. Causal theories to explain TB stigma were developed using a multi-country comparative approach, involving qualitative methods and the principles of grounded theory, alongside a realist conceptualisation of causality. Qualitative data was collected through 73 interviews with people with TB, their family members and health care providers in three rural and two urban sites in Bangladesh, Nepal and Pakistan, and through eight focus group discussions conducted in three of the sites. Three manifestations of TB stigma, for which causal theories were developed, were identified from the data: reduced marriage prospects, the perception that people with TB are hated, and the attribution of blame for the course and reoccurrence of TB. All three manifestations are rooted in different psychological processes and it is between these manifestations and their roots that the realist causal theories lie. The mechanisms and contexts which explain how, for whom and in what circumstances TB stigma becomes manifest provide the theory that can be used to underpin approaches to addressing TB stigma. These approaches focus on influencing the legitimacy of rejection, hatred and blame, on reducing vulnerability to TB, on empowering people with TB, and on mainstreaming TB stigma and pre-empting the changing nature of its manifestations.

This research provides a new assessment of Mertonâs classic strain/anomie theory and addresses some of its empirical and theoretical problems. First of all, it compares alternative operationalizations of classic strain and reports the results of a test of the theoryâs generality using the survey data from Ukrainian adolescents. Second, the research evaluates the chances of improving classic strain theory by elaborating and possibly integrating it with other explanations of crime and delinquency, particularly those featuring such constraints on behavior as perceptions of punishment, social bonds, self-control, and morality. The findings from this study confirm that additional clarifications of the concept of classic strain may be promising. They also demonstrate the applicability of Mertonâs account to the Ukrainian context and indicate the importance of socio-cultural macro-level influences. Furthermore, the results concerning the possibility of theoretical elaboration of the classic strain/anomie theory provide limited support for mediating or moderating effects of the constraint variables on the strain-crime relationship. However, they show that some measures of classic strain as well as all crime-inhibiting factors exert significant independent effects on involvement in juvenile delinquency. Therefore, empirical evidence seems to suggest that more drastic transformations of Mertonâs theory may be required in order to turn it into a more satisfying account of misbehavior. In particular, it indicates the necessity of theoretical integration of the classic strain/anomie explanation of crime with those featuring constraints on behavior.

A large number of studies show that educators are exposed to workloads that result particularly in stress. According to Olivier and Venter (2003), stress is considered to be the main factor contributing to job-related illnesses, early retirement, job dissatisfaction and absenteeism. Teaching, has without a doubt become a more demanding and stressful job. The lack of discipline in schools, abolishment of corporal punishment, large pupilteacher ratios and a new curriculum approach all contribute to raising the stress levels of teachers (Ngidi &
Sibaya, 2002). Stanton, Bachiochi, Robie, Perez and Smith (2002 cited in Brewer &
McMahan-Landers, 2003) is of the view that job stress is an antecedent of job satisfaction but the two constructs have been treated as related, yet they are different. The aim of this study is to determine the relationship between stress levels and job satisfaction amongst high school educators in De Aar as well as to 
determine whether biographical variables (namely, gender, age, tenure, marital status and number of children) have an impact on job satisfaction and stress levels. The researcher hopes that 
the findings would give the Department of Education in the Northern Cape an idea of the stress levels and job satisfaction experienced by high school educators in De Aar so that interventions can be implemented to issues proactively. The sample consisted of 86 educators employed at four high schools in De Aar. A biographical questionnaire, the Job Satisfaction Survey (JSS) and Stress Diagnostic Survey (SDS) were administered to assess respondents&rsquo
stress and job satisfaction levels. Informed consent was obtained from the various participants and anonymity of participation was ensured. Statistical analyses included inferential (Pearson&rsquo
s Product Moment Correlation Coefficient, Analysis of Variance &
T-Tests) as well as descriptive statistics. The results of the study 
indicate that there is a statistically significant, inverse relationship between stress levels and job satisfaction amongst high school educators in De Aar. Furthermore, the results indicate that there 
are statistically significant differences in stress levels as well as job satisfaction of high school educators on the basis of their biographical characteristics. The chapter concludes with presenting limitations of the study and putting forth recommendations for future research.

Forskning om entreprenörskap fokuserar på framgång som ignorerar den höga felfrekvensen av Nya företag. Många nya företag misslyckas så hur entreprenörer hantera det när deras företag misslyckas? Framgångsrika entreprenörer prisar fördelarna med misslyckande som en värdefull lärare. Resultatet av misslyckande regelbundet fylld med ekonomiska, sociala, psykologiska och fysiska hälsoproblem. Syftet med denna forskning är att bedöma företagets misslyckande upplevelser för företagare, från det ögonblick resultatet genom att  återhämtningen för att hantera företagande fel och avsluta för påverkan av den slutna företag.  I denna forskning aspekter av livet som påverka av entreprenörs fel undersöka ekonomiskt, socialt och psykologiskt att belysa faktorer som kan påverka mängden av kostnaderna för ett misslyckande. Därefter beskriver forskningen hur entreprenörer lära av misslyckanden. Den presenterar på resultaten av företagets misslyckande, inklusive hantera fel och återhämtning tillsammans med kognitiva och beteendemässiga utfall.
Research on entrepreneurship focuses on success which ignores the high failure rate of new ventures. Many new ventures fail so how entrepreneurs deal with it when their venture    fails? Successful entrepreneurs praising the advantages of failure as a valuable teacher. The result of failure is regularly filled with economic, social, psychological, and physical health disorder. The aim of this research is to assessment venture failure experiences for entrepreneurs, from the instant result through to recovery for coping with entrepreneurial failure and exit for impact of the closed venture. In this research, aspects of life affected by entrepreneurial failure examine economically, socially and psychologically in highlighting factors that may influence the amount of costs of failure. Next, the research describes how entrepreneurs learn from failure. It presents on the outcomes of venture failure, including coping with failure and recovery together with cognitive and behavioral outcomes. The main objective of the research study is to understand the failure from entrepreneurs    who have experienced it and also to make a theoretical framework of failure based on entrepreneurial venture failure experiences. Every entrepreneur starts up a venture with high expectations of achieving success. Failure can be emotionally disturbing, devastating,  painful, distressing and costly for the entrepreneur who may have to aspect the stigma of failure and the loss of reputation. The entrepreneur can get involved in grief, heartache, anxiety, depression, shame, rejection and discouragement (Politis & Gabrielsson, 2009). The purpose of the research is to investigate how entrepreneurs realize and react to venture  failure. Moreover, entrepreneurs are looking for positive aspects of failure as enhancing experiences that help their coping with entrepreneurial failure, learning from failure, the willingness to begin a new venture and also trigger changes in upcoming decision-making. The purpose of the research is to take a view of the existed experience of failure, taking into consideration impact from the entrepreneurship.

This thesis explores the phenomenon of irregular migration from the Brong Ahafo region of Ghana to Libya. It draws on migration theories to explain the underlying drivers of the phenomenon in the region. Many studies on irregular migration in Sub-Saharan Africa have predominantly attributed it to the push/pull theory. The objective here is to go beyond this stereotypical way of theorizing irregular migration in Sub-Saharan Africa by drawing on a wide range of migration theories to explain the underlying drivers of irregular migration from the Brong Ahafo region of Ghana to Libya. The evidence suggests that the drivers of irregular migration in the area under study are complex and nested in a broad-spectrum of social, cultural, moral, economic, historical, etc. context. Therefore, a single theory is inadequate to present a comprehensive explanation for the underlying drivers of the subject. It is revealed that there is the emergence of contemporary competing factors such as sports betting and internet fraud with some of the root causes of the phenomenon in the region. Hence, some of the root causes are weakened by these contemporary factors.

L’Afrique subsaharienne se présente, involontairement, comme une région en proie à une succession de crises, de conflits, de guerres civiles. Ces externalités négatives de l’instabilité socio-politique s’appréhendent, souvent, par le truchement du rite jaculatoire causal. D’où, les vocables « ethnies », « identité » – lorsqu’il n’est pas question de sous-développement, ou de l’injection du déficit démocratique –, auprès des commentateurs, sont, de façon cursive, convoqués pour expliquer le désordre perçu. Ainsi, les événements de 1994 au Rwanda sont ramenés à un conflit – « ethnique » – Hutu/Tutsi; négligeant par voie de conséquence l’acuité de la complexité de la réalité, ou à défaut, celle de la convergence de variables. Et pourtant, en descendant dans cette profondeur cognitive, tout observateur constaterait que l’instabilité socio-politique en Afrique subsaharienne reste une construction dans le temps et dans l’espace, optimisée par l’impénitent désir de pouvoir des acteurs politiques. Les structures historiques, loin d’être de véritables déterminants, participent à la construction sociale de la réalité porteuse d’idées, de règles et de pratiques représentationnelles qui érigent la nécessaire grammaire du bouleversement social. Nos présents travaux, non seulement, viennent examiner les causes habituellement avancées, mais s’opposent également aux arguments culturalistes mobilisés pour l’explication ou la compréhension de l’instabilité socio-politique en Afrique subsaharienne. C’est pourquoi, nous retenons que la justesse scientifique afférente à la compréhension du mouvement mécanistique socio-politique en Afrique subsaharienne est fonction du mode de connaissance de la réalité perçue. Par conséquent, nous estimons que l’instabilité socio-politique en Afrique subsaharienne, est un processus dynamique évolutif qui, nonobstant le désordre structurel, tend vers une stationnarité relative, puis absolue avant l’avènement de la stabilité
Subsaharan Africa presents itself, involuntarily, like an area in the grip of a succession of crises, conflicts, civil wars. These negative externalities of sociopolitical instability are apprehended, often, by the means of the causal ritual. That's why, the terms "ethnic group", "identity" - when it isn't question of underdevelopment, or the injection of democratic deficit - near the commentators, in a cursory mention, are convened to explain the perceived disorder. Thus, the events of 1994 in Rwanda are brought back to a "ethnic" conflict Hutu/Tutsi; negleging consequently the acuity of the complexity of reality or failing this, that of the convergence of variables. And yet, while going down in this cognitive depth, any observer would note that sociopolitical instability in subsaharan Africa remains a construction in time and space, optimized by the unrepentant desire of power of the political actors. The historical structures, far from being true determinants, take part in the social construction of reality carrying ideas, rules, and practices representational which set up the necessary grammar of the social upheaval. Our present work, not only comes to examine the usually advanced causes, but is also opposed to the culturalist arguments mobilized for the explanation or the comprehension of sociopolitical instability in subsaharan Africa. This is why, we retain that the scientific accuracy related with the comprehension of sociopolitical mechanisitc movement in subsaharan Africa is function of the mode of knowledge of perceived reality. Consequently, we estimate that sociopolitical instability in subsaharan Africa, is an evolutionary dynamic process which, notwhithstanding, the strutural disorder, strives for a relative stationnarity, then absolute before the advent of stability

thesis submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree Doctor of Philosophy. Johannesburg, 2013
Restless Legs Syndrome (RLS) and Periodic Limb Movements (PLM) are common neurological disorders for which the underlying aetiology is not fully understood. Currently RLS and PLM are thought to be caused by a central deficiency of dopamine or other functional abnormalities of the central nervous system. The work included in this thesis investigated different new methods of assessing the sensory and motor features of RLS and PLM, in an attempt to extend our understanding of their aetiology and improve the accuracy of diagnosis of these conditions. The first two studies in the thesis described and characterized the sensations of RLS symptoms, and whether they are influenced by the presence of pain, in an English speaking South African population. The most frequently cited descriptors were different to those used in the current RLS diagnostic criteria. Inclusion of the most commonly used RLS descriptors in the diagnostic criteria may help to improve the accuracy of RLS diagnosis. Patients who experienced painful RLS had greater McGill Pain Questionnaire scores and used different terms to describe their RLS to those that did not have painful RLS sensations. The third project quantified the responses of the Hoffman and patellar reflexes in RLS patients using electromyography and kinematics. The RLS patients exhibited hyporeflexia in the evening compared to the morning, and compared to control participants. This data suggests that RLS is not the result of a global state of hyperexcitability, as the literature suggests, but may reflect more discrete functional abnormalities of the spinal cord. A diurnal variation in the patellar reflex was found, supporting the notion of circadian variations of spinal excitability in RLS patients. The final investigation assessed the sensory qualities (discomfort and pain) of RLS in conjunction with motor activity evoked by using the Suggested Immobilization Test. Despite rating significant levels of discomfort, the majority of the RLS patients did not exhibit PLM; possibly suggesting a disconnect between the sensory and motor components of RLS. In conclusion, it is the major finding of this thesis that inclusion of new assessment techniques for the measurement of sensory and motor features of RLS and PLM provides both new insights and potential clinical tools enhancing our understanding of these disorders.

The primary intervention for injury in children traveling in cars in Australia has involved the mandatory use of a restraint while traveling in a vehicle. This intervention has been successful as evidenced by high restraint usage rates by Australian children and substantial casualty reductions since the 1970’s. However casualty rates have been relatively stagnant over the last couple of decades. Currently more than 3,000 child occupants are seriously injured in Australia every year. There is a need to examine the scope for further preventing injury among restrained child occupants. This thesis presents four interrelated studies examining the factors and mechanisms involved when Australian children are seriously injured while using some form of restraint in a crash. Methods used include retrospective medical record review, in-depth crash investigation and analysis of mass in-depth crash data. Both descriptive and nonparametric statistical analysis techniques, including those that allow for the control of potential confounders, were used. Observations and results indicate there is substantial scope for further reducing serious injury in children traveling in cars in Australia. To realize this reduction there is a need to address the quality of restraint use by children through the development of strategies that not only encourage restraint use, but encourage the correct use of the most appropriate forms of restraint. There is also a need to address the protection provided by restraint systems and vehicles to child occupants in high severity crashes, and in crashes that involve impacts with fixed roadside objects such as trees and poles.

Congenital heart disease (CHD) is characterized by structural defects of the heart and great vessels. It is the most common birth defect, affecting an estimated 1% of live births, and is the leading cause of mortality among birth defects. Despite recent progress in genetic research, more than 50% of CHD cases remain unexplained. An estimated 23% are due to aneuploidies and copy number variants and up to 30% has been attributed to de novo variation, though that number ranges between 3-30% depending on CHD complexity. The contribution of somatic mosaicism, or de novo genetic mutations arising after oocyte fertilization, to congenital heart disease (CHD) is not well understood due to limitations in sample size, detection method, and validation rate. Further, the relationship between mosaicism in blood and cardiovascular tissue has not been determined. We developed a computational method, Expectation-Maximization-based detection of Mosaicism (EM-mosaic), to analyze mosaicism in exome sequences of 2530 CHD proband-parent trios. EM-mosaic accurately detected 309 mosaic mutations in blood, with 85 of 94 (90%) candidates tested independently confirmed. We found twenty-five likely damaging mosaics in plausible CHD-risk genes, affecting 1% of our cohort. Variants in these genes predicted as damaging had higher variant allele fraction than benign variants, suggesting a role in CHD. The frequency of protein-coding mosaic variants detectable in blood was 0.122 or roughly 1 in 8 individuals. Analysis of 66 individuals with matched cardiac tissue available revealed both tissue-specific and shared mosaicism, with shared mosaics generally having higher allele fraction. CHD patients often present with comorbid cardiac and extracardiac anomalies that further their impact quality of life. Neurodevelopmental disorders (NDDs) are especially prevalent in CHD cases compared to the general population, yet the underlying genetic causes remain poorly explained. Further, patients with single ventricle defects undergoing surgery often later develop arrhythmias and experience worsening ventricular function. We used a statistical approach to dissect the association between de novo variation and these clinical outcomes and found that pleiotropic mutations contribute a large fraction of the risk of acquiring NDD and abnormal ventricular function phenotypes in CHD patients. We developed a proof-of-concept rare variant risk score that combines information from de novo, rare transmitted, and copy- number variants and show that prediction of outcomes such as NDD can be improved, especially in complex CHD cases.

Traditionally, cancer epidemiologists have investigated the causes of disease under the premise that patients with a certain site of disease can be treated as a single entity. Then risk factors associated with the disease are identified through case-control or cohort studies for the disease as a whole. However, with the rise of molecular and genomic profiling, in recent years biologic subtypes have increasingly been identified. Once subtypes are known, it is natural to ask the question of whether they share a common etiology, or in fact arise from distinct sets of risk factors, a concept known as etiologic heterogeneity. This dissertation seeks to evaluate methods for the study of etiologic heterogeneity in the context of cancer research and with a focus on methods for case-control studies. First, a number of existing regression-based methods for the study of etiologic heterogeneity in the context of pre-defined subtypes are compared using a data example and simulation studies. This work found that a standard polytomous logistic regression approach performs at least as well as more complex methods, and is easy to implement in standard software. Next, simulation studies investigate the statistical properties of an approach that combines the search for the most etiologically distinct subtype solution from high dimensional tumor marker data with estimation of risk factor effects. The method performs well when appropriate up-front selection of tumor markers is performed, even when there is confounding structure or high-dimensional noise. And finally, an application to a breast cancer case-control study demonstrates the usefulness of the novel clustering approach to identify a more risk heterogeneous class solution in breast cancer based on a panel of gene expression data and known risk factors.

Major developmental defects occur in 100,000 to 200,000 children born each year in the United States of America. 97% of these defects are from unidentified causes. Many fetal outcomes (e.g., developmental defects), result from interactions between genetic and environmental factors. The lifetime effects from prenatal exposures with low impact (e.g., air pollution) are often understudied. Even when these exposures are studied, the focus is often placed on immediate effects of the exposure (e.g., fetal anomalies, miscarriage rates) leaving lifetime effects largely unexplored. This makes prolonged (or lifetime) effects of low-impact exposures an understudied research area. Included in this set of low-impact exposures is seasonal variance at birth. This thesis measures the effects of seasonal variance at birth on lifetime disease risk at both the population-level and molecular-levels. Four aims, comprising this thesis study, were conducted that utilize data from pharmacology, clinical care (Electronic Health Records) and genetics. These aims included: 1.) Development of an Algorithm to Reveal Diseases with a Prenatal/Perinatal Seasonality Component (described in chapter 2); 2.) Investigation of Climate Variables that Affect Lifetime Disease Risk By Altering Environmental Drivers (described in chapters 3 and 4); 3.) Discovery of Genes Involved in Birth Season – Disease Effects (described in chapter 5) and 4.) Investigation of Pharmacological Inhibitors As Phenocopies of the Birth Season – Disease Effect (described in chapters 6 and 7). Knowledge gained from these four areas, through seven distinct studies, establishes that birth season is a causal risk factor in a number of common diseases including cardiovascular diseases.

Norman Geschwind, Albert M. Galaburda.
"A Bradford book." "Much of this book appeared as a three-part article in the 'Archives of neurology' volume 42, May, June, and July, 1985"--T.p. verso. Includes index.
Bibliography: p. [241]-273.

博士
國立屏東科技大學
生物資源研究所
96
The purpose of this study was to explore the effects of visitors’ moral norms and their perceptions of defensible space factors on vandalism in forest recreation areas. Moral norms include the moral emotions of guilt, shame, and embarrassment, together with techniques of neutralization intended to reduce the experience of these emotions. Perceived defensible space factors consist of perceived image, milieu, and symbolic barriers. The types of vandalism studied were littering and flower picking. Self-reported data was collected from 556 visitors to the Kenting, Tengchih, and Shuangliou forest recreation areas through questionnaires on moral norms, perceptions of defensible space factors, and vandalism. The data was analyzed using multiple regression analysis and slope analysis of response functions. The results indicated that visitors’ moral norms and their perceptions of defensible space factors significantly affected littering and flower picking. In addition, the results further showed the interference interaction between moral norms and perceived defensible space factors in a conditional effect plot. Specifically, visitors’ moral norms were not significantly related to littering and flower picking if they perceived higher defensible space factors, but their moral norms significantly influenced littering and flower picking if they perceived lower defensible space factors. Perceived defensible space factors were not significantly related to littering and flower picking for visitors with higher moral norms, but perceived defensible space factors significantly influenced littering and flower picking for visitors with lower moral norms. Implications of the results are discussed in the study.

The aim of this study was to investigate the causes and consequences of learner aggression in rural secondary schools in the Empangeni District of KwaZulu-Natal. The study also sought to establish the management strategies required to manage learner aggression in rural secondary schools. An in-depth literature study was conducted in this regard. A qualitative research design and methodology was adopted to investigate the phenomenon through an interview process with participants from five rural secondary schools. This study found that the causes of learner aggression were rooted in the family, the environment and the school. It was further established that the consequences of learner aggression were so serious that it resulted in victims experiencing intense fear, anxiety, tension, depression and ill-health. Furthermore, the findings of the empirical investigation concurred, to a large extent, with the findings of the literature study. Based on these findings, recommendations were made regarding the management of learner aggression in rural secondary schools.
Educational Leadership and Management
M. Ed. (Education Management)