DATA DRIVEN APPROACHES TO IDENTIFY DETERMINANTS OF HEART DISEASES AND CANCER RESISTANCE

Cancer and cardio-vascular diseases are the leading causes of death world-wide. Caused by systemic genetic and molecular disruptions in cells, these disorders are the manifestation of profound disturbance of normal cellular homeostasis. People suffering or at high risk for these disorders need early diagnosis and personalized therapeutic intervention. Successful implementation of such clinical measures can significantly improve global health. However, development of effective therapies is hindered by the challenges in identifying genetic and molecular determinants of the onset of diseases; and in cases where therapies already exist, the main challenge is to identify molecular determinants that drive resistance to the therapies. Due to the progress in sequencing technologies, the access to a large genome-wide biological data is now extended far beyond few experimental labs to the global research community. The unprecedented availability of the data has revolutionized the capabilities of computational researchers, enabling them to collaboratively address the long standing problems from many different perspectives. Likewise, this thesis tackles the two main public health related challenges using data driven approaches. Numerous association studies have been proposed to identify genomic variants that determine disease. However, their clinical utility remains limited due to their inability to distinguish causal variants from associated variants. In the presented thesis, we first propose a simple scheme that improves association studies in supervised fashion and has shown its applicability in identifying genomic regulatory variants associated with hypertension. Next, we propose a coupled Bayesian regression approach -- eQTeL, which leverages epigenetic data to estimate regulatory and gene interaction potential, and identifies combinations of regulatory genomic variants that explain the gene expression variance. On human heart data, eQTeL not only explains a significantly greater proportion of expression variance in samples, but also predicts gene expression more accurately than other methods. We demonstrate that eQTeL accurately detects causal regulatory SNPs by simulation, particularly those with small effect sizes. Using various functional data, we show that SNPs detected by eQTeL are enriched for allele-specific protein binding and histone modifications, which potentially disrupt binding of core cardiac transcription factors and are spatially proximal to their target. eQTeL SNPs capture a substantial proportion of genetic determinants of expression variance and we estimate that 58% of these SNPs are putatively causal. The challenge of identifying molecular determinants of cancer resistance so far could only be dealt with labor intensive and costly experimental studies, and in case of experimental drugs such studies are infeasible. Here we take a fundamentally different data driven approach to understand the evolving landscape of emerging resistance. We introduce a novel class of genetic interactions termed synthetic rescues (SR) in cancer, which denotes a functional interaction between two genes where a change in the activity of one vulnerable gene (which may be a target of a cancer drug) is lethal, but subsequently altered activity of its partner rescuer gene restores cell viability. Next we describe a comprehensive computational framework --termed INCISOR-- for identifying SR underlying cancer resistance. Applying INCISOR to mine The Cancer Genome Atlas (TCGA), a large collection of cancer patient data, we identified the first pan-cancer SR networks, composed of interactions common to many cancer types. We experimentally test and validate a subset of these interactions involving the master regulator gene mTOR. We find that rescuer genes become increasingly activated as breast cancer progresses, testifying to pervasive ongoing rescue processes. We show that SRs can be utilized to successfully predict patients' survival and response to the majority of current cancer drugs, and importantly, for predicting the emergence of drug resistance from the initial tumor biopsy. Our analysis suggests a potential new strategy for enhancing the effectiveness of existing cancer therapies by targeting their rescuer genes to counteract resistance. The thesis provides statistical frameworks that can harness ever increasing high throughput genomic data to address challenges in determining the molecular underpinnings of hypertension, cardiovascular disease and cancer resistance. We discover novel molecular mechanistic insights that will advance the progress in early disease prevention and personalized therapeutics. Our analyses sheds light on the fundamental biological understanding of gene regulation and interaction, and opens up exciting avenues of translational applications in risk prediction and therapeutics.

Examining underlying determinants of fertility rates in Zambia: Evidence from the 2007 Zambia Demographic and Health Survey

Limited data exits on factors influencing fertility in Zambia. This study examined underlying determinants of fertility patterns and levels in Zambia. Data extracted from the 2007 Zambia Demographic and Health Survey was analysed using bivariate and multivariate logistic regression. Of 7146 women aged 15-49 years, age group 25-29 years experienced the highest prevalence of births (28.5%). Married women accounted for 27% of all births. Women with low education recorded more births (27%) than those with higher education (9.5%) (P<0.001). Fertility was higher among the poorest (28%) compared to the richest (12%) (P<0.001). Though not statistically significant, urban areas recorded more births (25%) than rural areas (15%). Education and wealth significantly influence fertility Zambia. Fertility management strategies should consider these factors and their fertility reducing effects. Improving education and wealth status of women can contribute to fertility reduction, particularly rural women. Lower fertility, with reduced mortality and migration, would provide less pressure on distribution of the limited economic resources of the country.

Determinants of transfer of training: A comprehensive literature review

Investments in training measures can only be considered effective if the transfer of the learned contents to practical situations is continuously successful. In this context the scientific and professional discourse regarding the effectiveness of further education, especially regarding training transfer, has intensified considerably. This analysis provides a systematic and comprehensive overview of the current state of international empirical research regarding major influencing factors of learning transfer in the context of formalized further vocational training. Our review of literature differentiates the most important influencing factors on the micro-level of the specific individual characteristics of the participants, the meso-level of measure-specific characteristics of the field of learning, as well as institutional characteristics of the work environment at the macro-level. Decades of transfer research brings forth a wealth of information regarding factors which influence the learning transfer. The current analysis systematizes these results and clarifies that the current state of research regarding the determinants of the process of learning transfer shows clear trends. But there are also some inconsistent findings. Thus the question of which factors positively influence the success of learning transfer is well-studied for the micro-level in particular. The article shows that there is still a research deficit concerning the major determinants of learning transfer at the meso- and macro-level. Finally, in this context this article identifies promising directions for future research. (DIPF/Orig.)

Determinants of alcohol use and khat chewing among Hawassa University students, Ethiopia: a cross sectional study.

Background: Students’ alcohol and khat use have been associated with various health related problems. However, its magnitude and associated factors among Ethiopian students are not yet well documented. Objective: The study aimed to assess the prevalence of alcohol use, khat chewing and its associated factors among Hawassa University students. Methods: A cross-sectional study was conducted from June to July 2011. Multistage stratified sampling technique was employed to select 590 students. Self administered questionnaires were used to collect data. Data was entered and analysed by SPSS version 20.0. Logistic regression analyses were used to identify the association of different variables. Results: The current prevalence of student’s alcohol and khat use were 29.5% (95% CI: 25.8-33.3) and 16.3% (95% CI: 13.7- 20.0) respectively. Being male (AOR 1.8; 95% CI 1.1-3.0) and living alone (AOR 20.1; 95% CI 2.5-166.7) had a higher odds of alcohol use. Similarly, family substance use history (AOR 4.8; 95% CI 2.5-9.3) and peer influence (AOR 4.6; 95% CI 2.3-9.0) had also higher odds of khat use. Conclusion and recommendation: The proportion of student’s khat chewing and alcohol use was significant. Hence, higher education in collaboration with other stakeholders should work on convincing students about the ill effects of these substances.

DETERMINANTS OF THE ADOPTION OF INTEGRATED SOIL FERTILITY MANAGEMENT TECHNOLOGIES IN MBALE DIVISION, KENYA

The agro-climatic conditions in western Kenya present the region as a food surplus area yet people are still reliant on food imports, with the region registering high poverty levels. Depletion of soil fertility and the resulting decline in agricultural productivity in Mbale division has led to many attempts to develop and popularize Integrated Soil Fertility Management (ISFM) technologies that could restore soil fertility. These technologies bridge the gap between high external inputs and extreme forms of traditional low external input agriculture. Some of the ISFM components used by farmers are organic and inorganic inputs and improved seeds. However, the adoption of these technologies is low. The study aimed to examine the factors that influence the adoption of ISFM technologies by smallholder farmers in Mbale division, Kenya. The study was conducted in 9 sub-locations in Mbale division. Purposive sampling was used in selecting the 80 farmers to get the data based on a farm-household survey. Self-administered questionnaires were used to collect data on the determinants of the adoption of ISFM technologies from the sampled farmers in the study area. The study sought to answer the research question: What factors influence the uptake of ISFM technologies by farmers in Mbale division? The hypothesis tested was that the adoption of ISFM technologies is not influenced by age, education, extension services, labour, off-farm income and farm size. Data was analyzed using descriptive statistics. Cross tabulation was used for examining the relationship between categorical (nominal or ordinal) variables, and the bivariate correlations procedure was used to compute the pair wise associations between scale or ordinal variables. Probit regression was used to predict the socio-economic factors influencing the adoption of ISFM technologies among smallholder farmers. Results of the study indicated that education of household head, membership in social groups, age of the household head, off-farm income and farm size were the variables that significantly influenced the adoption of ISFM technologies. The findings show that there is need for a more pro-poor focused approach to achieve sustainable soil fertility management among smallholder farmers. The findings will help farmers, extension officers, researchers and donors in identifying region-specific entry points that can help in developing innovative ISFM technologies.

EDUCATION, TRAINING AND AWARENESS OF LAWS AS DETERMINANTS OF COMPLIANCE WITH PLANT PROTECTION LAW: THE CASE OF PESTICIDE USE PRACTICES IN TANZANIA

Pesticide residues in food and environment pose serious health risks to human beings. Plant protection laws, among other things, regulate misuse of agricultural pesticides. Compliance with such laws consequently reduces risks of pesticide residues in food and the environment. Studies were conducted to assess the compliance with plant protection laws among tomato farmers in Mvomero District, Morogoro Region, Tanzania. Compliance was assessed by examining pesticide use practices that are regulated by the Tanzanian Plant Protection Act (PPA) of 1997. A total of 91 tomato farmers were interviewed using a structured questionnaire. Purposive sampling was used in selecting at least 30 respondent farmers from each of the three villages of Msufini, Mlali and Doma in Mvomero District, Morogoro Region. Simple Random Sampling was used to obtain respondents from the sampling frame. Individual and social factors were examined on how they could affect pesticide use practices regulated by the law. Descriptive statistics, mainly frequency, were used to analyze the data while associations between variables were determined using Chi-Square and logistic regression model. The results showed that respondents were generally aware of the existence of laws on agriculture, environment and consumer health, although none of them could name a specific Act. The results revealed further that 94.5% of the farmers read instructions on the pesticides label. However, only 21% used the correct doses of pesticides, 40.7% stored pesticides in special stores, 68.1% used protective gear, while 94.5% always read instructions on the label before using a pesticide product. Training influenced the application rate of pesticide (p < 0.001) while awareness of agricultural laws significantly influenced farmers’ tendency to read information on the labels (p < 0.001). The results showed further that education significantly influenced the use of protective gears by farmers (p = 0.042). Education also significantly affected the manner in which farmers stored pesticide-applying equipment (p = 0.024). Furthermore, farmers’ awareness of environmental laws significantly (p = 0.03) affected farmers’ disposal of empty pesticide containers. Results of this study suggest the need for express provisions on safe use and handling of pesticides and related offences in the Act, and that compliance should be achieved through education rather than coercion. Results also suggest establishment of pesticide disposal mechanisms and structures to reduce unsafe disposal of pesticide containers. It is recommended that farmers should be educated and trained on proper use of pesticides. Farmers’ awareness on laws affecting food, environment and agriculture should be improved.

ASSESSING THE DETERMINANTS OF TISSUE CULTURE BANANA ADOPTION IN WESTERN KENYA

In this study cross-section data was used to analyze the effect of farmers’ demographic, socioeconomic and institutional setting, market access and physical attributes on the probability and intensity of tissue culture banana (TCB) adoption. The study was carried out between July 2011 and November 2011. Both descriptive (mean, variance, promotions) and regression analysis were used in the analysis. A double hurdle regression model was fitted on the data. Using multistage sampling technique, four counties and eight sub-locations were randomly selected. Using random sampling technique, three hundred and thirty farmers were selected from a list of banana households in the selected sub-locations. The adoption level of tissue culture banana (TCB) was about 32%. The results also revealed that the likelihood of TCB adoption was significantly influenced by: availability of TCB planting material, proportion of banana income to the total farm income, per capita household expenditure and the location of the farmer in Kisii County; while those that significantly influenced the intensity of TCB adoption were: occupation of farmers, family size, labour source, farm size, soil fertility, availability/access of TCB plantlets to farmers, distance to banana market, use of manure in planting banana, access to agricultural extension services and index of TCB/non-TCB banana cultivar attributes which were scored by farmers. Compared to West Pokot County, farmers located in Bungoma County are more significantly and likely to adopt TCB technology. Therefore, the results of the study suggest that the probability of adoption and intensity of the use of TCB should be enhanced. This can be done by taking cognizance of these variables in order to meet the priority needs of the smallholder farmers who were the target group. This would lead to alleviating banana shortage in the region for enhanced food security. Subsequently, actors along the banana value chain are encouraged to target the intervention strategies based on the identified farmer, farm and institutional characteristics for enhanced impact on food provision. Opening up more TCB multiplication centres in different regions will make farmers access the TCB technology for enhanced impact on the target population.

Determinants of engagement in virtual social networks in Singapore

The use of virtual social networks (VSNs) has been prevalent among consumers worldwide. Numerous studies have investigated various aspects of VSNs. However, these studies have mainly focused on students and young adults as they were early adopters of these innovative networks. A search of the literature revealed there has been a paucity of research on adult consumers’ use of VSNs. This research study addressed this gap in the literature by examining the determinants of engagement in VSNs among adult consumers in Singapore. The objectives of this study are to empirically investigate the determinants of engagement in VSNs and to offer theoretical insights into consumers’ preference and usage of VSNs. This study tapped upon several theories developed in the discipline of technology and innovation adoption. These were Roger’s Diffusion of Innovation, Theory of Reasoned Action (TRA), Theory of Planned Behavior (TPB), Technology Acceptance Model (TAM), Conceptual Framework of Individual Innovation Adoption by Frambach and Schillewaert (2002), Enhanced Model of Innovation Adoption by Talukder (2011), Extended Unified Theory of Acceptance and Use of Technology (UTAUT2) and the Information Systems (IS) Success Model. The proposed research model, named the Media Usage Model (MUM), is a framework rooted in innovation diffusion and IS theories. The MUM distilled the essence of these established models and thus provides an updated, lucid explanation of engagement in VSNs. A cross-sectional, online social survey was conducted to collect quantitative data to examine the validity of the proposed research model. Multivariate data analysis was carried out on a data set comprising 806 usable responses by utilizing SPSS, and for structural equation modeling AMOS and SmartPLS. The results indicate that consumer attitude towards VSNs is significantly and positively influenced by: three individual factors – hedonic motivation, incentives and experience; two system characteristics – system quality and information quality; and one social factor – social bonding. Consumer demographics were found to influence people’s attitudes towards VSNs. In addition, consumer experience and attitude towards VSNs significantly and positively influence their usage of VSNs. The empirical data supported the proposed research model, explaining 80% of variance in attitude towards VSNs and 45% of variance in usage of VSNs. Therefore, the MUM achieves a definite contribution to theoretical knowledge of consumer engagement in VSNs by deepening and broadening our appreciation of the intricacies related to use of VSNs in Singapore. This study’s findings have implications for customer service management, services marketing and consumer behavior. These findings also have strategic implications for maximizing efficient utilization and effective management of VSNs by businesses and operators. The contributions of this research are: firstly, shifting the boundaries of technology or innovation adoption theories from research on employees to consumers as well as the boundaries of Internet usage or adoption research from students to adults, which is also known as empirical generalization; secondly, highlighting the issues associated with lack of significance of social factors in adoption research; and thirdly, augmenting information systems research by integrating important antecedents for success in information systems.

The determinants of VAT revenues in Portugal

Mestrado em Finanças

Macroeconomic determinants of contingent protection:the case of the European Union

Contingent Protection has grown to become an important trade restricting device. In the European Union, protection instruments like antidumping are used extensively. This paper analyses whether macroeconomic pressures may contribute to explain the variations in the intensity of antidumping protectionism in the EU. The empirical analysis uses count data models, applying various specification tests to derive the most appropriate specification. Our results suggest that the filing activity is inversely related to the macroeconomic conditions. Moreover, they confirm existing evidence for the US suggesting that domestic macroeconomic pressures are a more important determinant of contingent protection policy than external pressures.

Determinants Of Firm Terminal Value: The Perspective Of North American And European Financial Analysts

Company valuation models attempt to estimate the value of a company in two stages: (1) comprising of a period of explicit analysis and (2) based on unlimited production period of cash flows obtained through a mathematical approach of perpetuity, which is the terminal value. In general, these models, whether they belong to the Dividend Discount Model (DDM), the Discount Cash Flow (DCF), or RIM (Residual Income Models) group, discount one attribute (dividends, free cash flow, or results) to a given discount rate. This discount rate, obtained in most cases by the CAPM (Capital asset pricing model) or APT (Arbitrage pricing theory) allows including in the analysis the cost of invested capital based on the risk taking of the attributes. However, one cannot ignore that the second stage of valuation that is usually 53-80% of the company value (Berkman et al., 1998) and is loaded with uncertainties. In this context, particular attention is needed to estimate the value of this portion of the company, under penalty of the assessment producing a high level of error. Mindful of this concern, this study sought to collect the perception of European and North American financial analysts on the key features of the company that they believe contribute most to its value. For this feat, we used a survey with closed answers. From the analysis of 123 valid responses using factor analysis, the authors conclude that there is great importance attached (1) to the life expectancy of the company, (2) to liquidity and operating performance, (3) to innovation and ability to allocate resources to R&D, and (4) to management capacity and capital structure, in determining the value of a company or business in long term. These results contribute to our belief that we can formulate a model for valuating companies and businesses where the results to be obtained in the evaluations are as close as possible to those found in the stock market

Determinants of Terminal Value in the Evaluation of Companies: A Panel Data Approach to the Context of European Companies.

The uncertainty of the future of a firm has to be modelled and incorporated into the evaluation of companies outside their explicit period of analysis, i.e., in the continuing or terminal value considered within valuation models. However, there is a multiplicity of factors that influence the continuing value of businesses which are not currently being considered within valuation models. In fact, ignoring these factors may cause significant errors of judgment, which can lead models to values of goodwill or badwill, far from the substantial value of the inherent assets. Consequently, these results provided will be markedly different from market values. So, why not consider alternative models incorporating life expectancy of companies, as well as the influence of other attributes of the company in order to get a smoother adjustment between market price and valuation methods? This study aims to provide a contribution towards this area, having as its main objective the analysis of potential determinants of firm value in the long term. Using a sample of 714 listed companies, belonging to 15 European countries, and a panel data for the period between 1992 and 2011, our results show that continuing value cannot be regarded as the current value of a constant or growth perpetuity of a particular attribute of the company, but instead be according to a set of attributes such as free cash flow, net income, the average life expectancy of the company, investment in R&D, capabilities and quality of management, liquidity and financing structure.

Barriers and facilitators to initial and continued attendance at community-based lifestyle programmes among families of overweight and obese children: a systematic review

The success of childhood weight management programmes relies on family engagement. While attendance offers many benefits including the support to make positive lifestyle changes, the majority of families referred to treatment decline. Moreover, for those who do attend, benefits are often compromised by high programme attrition. This systematic review investigated factors influencing attendance at community-based lifestyle programmes among families of over-weight or obese children. A narrative synthesis approach was used to allow for the inclusion of quantitative, qualitative and mixed-method study designs. Thirteen studies met the inclusion criteria. Results suggest that parents provided the impetus for programme initiation, and this was driven largely by a concern for their child's psychological health and wellbeing. More often than not, children went along without any real reason or interest in attending. Over the course of the programme, however, children's positive social experiences such as having fun and making friends fostered the desire to continue. The stigma surrounding excess weight and the denial of the issue amongst some parents presented barriers to enrolment and warrant further study. This study provides practical recommendations to guide future policy makers, programme delivery teams and researchers in developing strategies to boost recruitment and minimise attrition.

Force determinants of sit-to-stand transfer in patients with haemophilic arthropathy: Cross-sectional study

SIN FINANCIACIÓN