Hepatocyte determinants of susceptibility to pre-erythrocytic Plasmodium infection

Thesis (Ph.D.)--University of Washington, 2016-08

Is "football for all" safe for all? : Cross-Sectional Study of Disparities as Determinants of 1-Year Injury Prevalence in Youth Football Programs

Football (soccer) is endorsed as a health-promoting physical activity worldwide. When football programs are introduced as part of general health promotion programs, equal access and limitation of pre-participation disparities with regard to injury risk are important. The aim of this study was to explore if disparity with regard to parents' educational level, player body mass index (BMI), and self-reported health are determinants of football injury in community-based football programs, separately or in interaction with age or gender. Methodology/Principal Findings Four community football clubs with 1230 youth players agreed to participate in the cross-sectional study during the 2006 season. The study constructs (parents' educational level, player BMI, and self-reported health) were operationalized into questionnaire items. The 1-year prevalence of football injury was defined as the primary outcome measure. Data were collected via a postal survey and analyzed using a series of hierarchical statistical computations investigating associations with the primary outcome measure and interactions between the study variables. The survey was returned by 827 (67.2%) youth players. The 1-year injury prevalence increased with age. For youths with parents with higher formal education, boys reported more injuries and girls reported fewer injuries than expected; for youths with lower educated parents there was a tendency towards the opposite pattern. Youths reporting injuries had higher standardized BMI compared with youths not reporting injuries. Children not reporting full health were slightly overrepresented among those reporting injuries and underrepresented for those reporting no injury. Conclusion Pre-participation disparities in terms of parents' educational level, through interaction with gender, BMI, and self-reported general health are associated with increased injury risk in community-based youth football. When introduced as a general health promotion, football associations should adjust community-based youth programs to accommodate children and adolescents with increased pre-participation injury risk.

A systematic review of methods to assess intake of fruits and vegetables among healthy European adults and children: a DEDIPAC (DEterminants of DIet and Physical Activity) study

Evidence suggests that health benefits are associated with consuming recommended amounts of fruits and vegetables (F&V), yet standardised assessment methods to measure F&V intake are lacking. The current review aims to identify methods to assess F&V intake among children and adults in pan-European studies and inform the development of the DEDIPAC (DEterminants of DIet and Physical Activity) toolbox of methods suitable for use in future European studies. A literature search was conducted using three electronic databases and by hand-searching reference lists. English-language studies of any design which assessed F&V intake were included in the review. Studies involving two or more European countries were included in the review. Healthy, free-living children or adults. The review identified fifty-one pan-European studies which assessed F&V intake. The FFQ was the most commonly used (n 42), followed by 24 h recall (n 11) and diet records/diet history (n 7). Differences existed between the identified methods; for example, the number of F&V items on the FFQ and whether potatoes/legumes were classified as vegetables. In total, eight validated instruments were identified which assessed F&V intake among adults, adolescents or children. The current review indicates that an agreed classification of F&V is needed in order to standardise intake data more effectively between European countries. Validated methods used in pan-European populations encompassing a range of European regions were identified. These methods should be considered for use by future studies focused on evaluating intake of F&V.

A systematic review of methods to assess intake of sugar-sweetened beverages among healthy European adults and children: a DEDIPAC (DEterminants of DIet and Physical Activity) study

Research indicates that intake of sugar-sweetened beverages (SSB) may be associated with negative health consequences. However, differences between assessment methods can affect the comparability of intake data across studies. The current review aimed to identify methods used to assess SSB intake among children and adults in pan-European studies and to inform the development of the DEDIPAC (DEterminants of DIet and Physical Activity) toolbox of methods suitable for use in future European studies. A literature search was conducted using three electronic databases and by hand-searching reference lists. English-language studies of any design which assessed SSB consumption were included in the review. Studies involving two or more European countries were included in the review. Healthy, free-living children and adults. The review identified twenty-three pan-European studies which assessed intake of SSB. The FFQ was the most commonly used (n 24), followed by the 24 h recall (n 6) and diet records (n 1). There were several differences between the identified FFQ, including the definition of SSB used. In total, seven instruments that were tested for validity were selected as potentially suitable to assess SSB intake among adults (n 1), adolescents (n 3) and children (n 3). The current review highlights the need for instruments to use an agreed definition of SSB. Methods that were tested for validity and used in pan-European populations encompassing a range of countries were identified. These methods should be considered for use by future studies focused on evaluating consumption of SSB.

Key determinants of organisational silence for non-standard workers

Purpose – The purpose of this paper is to identify the key determinants of organisational silence from the perspective of non-standard workers (NSWs). The study focuses on three research themes: first, analysing the experiences motivating NSWs to remain silent; second, analysing the role of the NSW life cycle in the motivation to remain silent, the final theme is evaluation of the impact on organisational voice of an organisation employing a workforce in which NSWs and standard workers (SWs) are blended. Design/methodology/approach – The study utilises a phenomenological approach, as defined by Van Manen (2007), to collect and analyse the phenomenon of organisational silence from the perspective of NSWs. The NSWs are defined as individuals operating via Limited Liability UK registered companies created for the purpose of delivering services to organisations via a contract of services. This study employed a combination of phenomenology and hermeneutics to collect and analyse the data collected from the NSWs using semi-structured interviews (Lindseth and Norberg, 2004). Findings – The study concludes with three core findings. NSWs experience similar motivational factors to silence as experienced by standard workers (SWs). The key differential between a SW and a NSW is the role of defensive silence as a dominant motivator for a start-up NSW. The study identified that the reasons for this is that new NSWs are defensive to protect their reputation for any future contract opportunities. In addition, organisations are utilising the low confidence of new start up NSWs to suppress the ability of NSWs to voice. The research indicates how experienced NSWs use the marketing stage of their life cycle to establish voice mechanisms. The study identified that NSWs, fulfiling management and supervisory roles for organisations, are supporting/creating climates of silence through their transfer of experiences as SWs prior to becoming NSWs. Research limitations/implications – This study is a pilot study, and the findings from this study will be carried forward into a larger scale study through engagement with further participants across a diverse range of sectors. This study has identified that there is a need for further studies on organisational silence and NSWs to analyse more fully the impact of silence on the individuals and the organisation itself. A qualitative phenomenological hermeneutical study is not intended to be extrapolated to provide broad trends. The focus of the phenomenological hermeneutic research methodology is on describing and analysing the richness and depth of the NSW’s experiences of silence in organisational settings. Originality/value – This paper draws together the studies of worker classification, motivators for organisational silence, and the impact of blending SWs and NSWs in an organisational setting. The study demonstrates that academic research to date has focused predominantly on SWs to the exclusion of the 1.5 million, and growing, NSWs in the UK. This study examines these under-represented workers to analyse the participants’ experiences of organisational silence, and its consequences in organisational settings, demonstrating a need for further studies.

Quantifying Barriers to Meditation as a Health Behavior: Exploratory and Confirmatory Factor Analysis of the Determinants of Meditation Practice Inventory

Although the benefits of mindfulness meditation practices have been widely documented, research data suggest that there are barriers to regularly engaging in meditation behavior. In order to explore research questions pertaining to meditation initiation and adherence, psychometrically valid scales to assess barriers to meditation practice are necessary. The aim of the present study was to explore the factor structure and construct validity of the Determinants of Meditation Practice Inventory (DMPI) (Williams et al., 2011), a perceived barriers to meditation scale. Exploratory and confirmatory factor analyses along with construct validity tests were performed on data obtained from two large, community samples. Results supported the DMPI as a valid scale assessing perceived barriers with four factors, Lack of Interest, Knowledge Concerns, Pragmatic Concerns and Sociocultural Beliefs. The present study offers a DMPI-revised scale that may be reliably used to assess attitudes and beliefs that might impede meditation behavior.

Determinants of self-medication with NSAIDs in a Portuguese community pharmacy

Background: Non-steroid anti-inflammatory drugs (NSAIDs) are a widely used therapeutic group in the world, and particularly in the Portuguese population. Objective: To compare NSAID’s use by prescription and self-medication acquisition and to determine the pattern of indication of NSAIDs, their usage profile and possible implications for patients’ safety. Methods: A cross-sectional design was used where individuals presenting at a community pharmacy requesting NSAIDs during the study period (one month) were invited to answer a face-to-face interview where socio-demographic characteristics, the indication pattern and previous experience of side effects were assessed. A follow-up interview was performed one week later to assess the incidence of adverse effects. The study was ethically approved. Results: A sample of 130 NSAIDs users was recruited, comprising mostly women (n=87; 66.9%), actively employed (n=77; 59.2%) and presenting a mean age of 49.5 years old (SD=20.49). An equal proportion of individuals acquired NSAIDs by self-medication and with medical prescription (n=65; 50%). Over 4/5 of patients (n=57; 87.7%) acquiring NSAIDs without a prescription were self-medicated by their own initiative, and only 10.8% (n=7) had been advised by the pharmacist. The most commonly acquired active substances were ibuprofen and diclofenac. Self-medicated users more frequently resorted to topical NSAIDs following short term treatments. The major underlying condition motivating NSAIDs sought were musculoskeletal disorders (45.0%), regardless of the regimen. An important proportion of prevalent users of NSAIDs reported previous experience of adverse effects (11.3%). One week after initiating NSAID therapy, a small proportion of patients reported incidence of adverse effects. Conclusion: Self-medication with NSAIDs is sought for numerous medical conditions. Reported adverse effects (prevalent and incident) confirm the need for a more rational use of NSAIDs and ongoing pharmacovigilance.

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.