Mindfulness and Spirituality as determinants of Existential Loneliness in the Dutch

Existential loneliness is a concept that is largely ignored in the psychological research tradition, although from a philosophical perspective it is deeply connected to inherent human longings of connection and meaning. This research investigated the relationship between existential loneliness and two variables that are theoretically closely related to the concepts of connection and meaning, namely mindfulness (connection to oneself and others) and spiritual well-being (connection to a larger whole). This was done in a sample of n = 180 individuals (61.7% female; mean age 41.72, SD = 12.16) of the Dutch population. A multiple regression analysis was conducted. It can be concluded that there is a negative relationship between mindfulness and existential loneliness, as well as between spiritual well-being and existential loneliness. This means that people with a higher level of mindfulness and/or a higher level of spiritual well-being experience a lower level of existential loneliness. At the same time, people with a lower level of mindfulness and/or spiritual well-being experience a lower level of existential loneliness. There are some limitations to this study, for example the use of a non-random sampling method, a limited sample group, a scale that has not been widely tested, and a potential bias towards the higher educated. However, these limitations are inherent to exploratory research and does not diminish the main strength of this thesis, namely that it has provided more insight into an important and prevalent societal phenomenon, that had not been extensively researched previously, that has so far only been addressed in more philosophical instead of scientific debates, and linked almost exclusively to negative concepts, such as terminal illness. This research provides a first understanding of two positive determinants of existential loneliness, which could potentially be used to help make sense of this inherently humane condition, as well as to actively cope with the potential (adverse) effects of it.

Insight into determinants of substrate binding and transport in a multidrug efflux protein

Multidrug resistance arising from the activity of integral membrane transporter proteins presents a global public health threat. In bacteria such as Escherichia coli, transporter proteins belonging to the major facilitator superfamily make a considerable contribution to multidrug resistance by catalysing efflux of myriad structurally and chemically different antimicrobial compounds. Despite their clinical relevance, questions pertaining to mechanistic details of how these promiscuous proteins function remain outstanding, and the role(s) played by individual amino acid residues in recognition, binding and subsequent transport of different antimicrobial substrates by multidrug efflux members of the major facilitator superfamily requires illumination. Using in silico homology modelling, molecular docking and mutagenesis studies in combination with substrate binding and transport assays, we identified several amino acid residues that play important roles in antimicrobial substrate recognition, binding and transport by Escherichia coli MdtM, a representative multidrug efflux protein of the major facilitator superfamily. Furthermore, our studies suggested that 'aromatic clamps' formed by tyrosine and phenylalanine residues located within the substrate binding pocket of MdtM may be important for antimicrobial substrate recognition and transport by the protein. Such 'clamps' may be a structurally and functionally important feature of all major facilitator multidrug efflux proteins.

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.

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.

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.

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 the Design and Use of PMS in Portuguese Government Agencies: A Complementary Theoretical Approach

Performance measurement is seen as a main pillar of public management reforms. However, prior research did not mitigate the level of ambiguity on PMS development and use and many questions left unanswered. Our findings provide knowledge on the design and use of PMS in the public sector answer- ing to calls for a complementary approach among institutional and contingency factors. The authors find that the design of PMS and the use of performance information for external purposes are increased to legitimate the organizational’ work and to obtain external support. Moreover, structural variables such as type of agency and management autonomy are also determinants on the organizational responses. Finally, the authors find some coupling between the design of PMS and outcomes. So, both contingent and institutional approaches play an important role on the empirical model.

Determinants of Sustainability e-reporting in Portuguese municipalities: an institutional and legitimacy theoretical framewor

This study aims to analyse the extent of online social responsibility (SR) information disclosure by Portuguese municipalities and to identify related determinant factors, based on Institutional Theory and Legitimacy Theories. A content analysis was performed on webpages from 60 sampled municipalities, and an information disclosure index was created.Descriptive statistics obtained indicate the Total Disclosure Index (TDI) value was 0.46. The Economic Information sub-category exhibits the highest value (0.66), followed by the Social and Environmental Information categories (0.61 and 0.36, respectively). The multivariate analysis results indicate that LA21 implementation the existence of tax burdens, the characterisation of a municipality as urban and environmental/SR certification application positively influence SR information disclosure. TDI is negatively affected by the existence of an inactive population (i.e. by the percentage of individuals ≤19 and ≥65 years of age).

Determinants of environmental accounting and reporting practices in portuguese local entities

Purpose – The purpose of this paper is to develop environmental accounting and reporting practices (EARPs) by Portuguese local entities and their determining factors. Design/methodology/approach – Data were obtained through a postal survey. In order to measure the degree of development of environmental accounting and reporting practices index was developed, which reflects the extent to which a set of eight EARPs have been implemented by the 69 Portuguese local entities included in the sample. Three variables are considered in this study as possible factors that drive the development of environmental management practices (EMPs) by local entities, namely, size of entity, accounting framework, degree of development of EMPs. Findings – Results indicate the degree of development of EARPs in Portuguese local entities is low. Additionally, accounting regulation and the degree of development of EMPs are explaining factors of the degree of development of environmental accounting practices in Portuguese local entities. Originality/value – This study adds to the international research on environmental accounting in public sector by providing empirical data from a country, Portugal, where empirical evidence is still relatively limited.

The Determinants of Individual Performance: Empirical Essays on the Importance of Soft Skills and Monetary Incentives

This dissertation consists of three papers. The first paper "Managing the Workload: an Experiment on Individual Decision Making and Performance" experimentally investigates how decision-making in workload management affects individual performance. I designed a laboratory experiment in order to exogenously manipulate the schedule of work faced by each subject and to identify its impact on final performance. Through the mouse click-tracking technique, I also collected interesting behavioral measures on organizational skills. I found that a non-negligible share of individuals performs better under externally imposed schedules than in the unconstrained case. However, such constraints are detrimental for those good in self-organizing. The second chapter, "On the allocation of effort with multiple tasks and piecewise monotonic hazard function", tests the optimality of a scheduling model, proposed in a different literature, for the decisional problem faced in the experiment. Under specific assumptions, I find that such model identifies what would be the optimal scheduling of the tasks in the Admission Test. The third paper "The Effects of Scholarships and Tuition Fees Discounts on Students' Performances: Which Monetary Incentives work Better?" explores how different levels of monetary incentives affect the achievement of students in tertiary education. I used a Regression Discontinuity Design to exploit the assignment of different monetary incentives, to study the effects of such liquidity provision on performance outcomes, ceteris paribus. The results show that a monetary increase in the scholarships generates no effect on performance since the achievements of the recipients are all centered near the requirements for non-returning the benefit. Secondly, students, who are actually paying some share of the total cost of college attendance, surprisingly, perform better than those whose cost is completely subsidized. A lower benefit, relatively to a higher aid, it motivates students to finish early and not to suffer the extra cost of a delayed graduation.

Insight into the molecular and functional determinants of HP1043, the essential master regulator of Helicobacter pylori.

Helicobacter pylori is one of the most widespread and successful human pathogens, colonizing half of the population stomach mucosa and causing gastric malignancies in 1% of carriers. Due to the increasing number of antimicrobial-resistant strains, in 2017 the WHO included H. pylori among pathogens that pose a major threat for humankind. In this study, we propose as a molecular target for novel antimicrobial strategies HP1043, an orphan response regulator essential for the viability of H. pylori as it orchestrates all the most important cellular processes. Amino acids most relevant for HP1043 dimerization and target DNA recognition were identified and used to guide an in-silico protein-DNA docking and generate a high-resolution structural model of the interacting HP1043 dimer and its target DNA. The model was experimentally validated and exploited to carry out a virtual screening of small molecule libraries, identifying 8 compounds potentially able to interfere with HP1043 function and likely block H. pylori infection. A second line of research aimed at the characterization of the regulatory function of HP1043 and the tight mechanisms of regulation of hp1043 gene expression. In particular, we proved a direct interaction between HP1043 and the housekeeping sigma80 factor of the RNA polymerase. A conditional mutant H. pylori strain overexpressing a synthetic copy of the hp1043 gene altered in nucleotide sequence yet encoding the wild-type protein was generated, achieving increased intracellular levels of HP1043. However, overexpression of HP1043 did not result in an upregulation of target genes transcription nor modulation of hp1043 transcript levels, pinpointing the existence of multiple overlayed mechanisms of regulation that affect both protein levels and functionality as well as maintain steady the amount of hp1043 transcript. Finally, we proposed that a mechanism of post-transcriptional regulation could depend on an antisense transcript to the hp1043 gene which was validated in two different strains.

Clinicopathological And Immunohistochemical Evaluation Of Oral And Oropharyngeal Squamous Cell Carcinoma In Chilean Population.

In oral and oropharyngeal squamous cell carcinoma (OCSCC and OPSCC) exist an association between clinical and histopathological parameters with cell proliferation, basal lamina, connective tissue degradation and surrounding stroma markers. We evaluated these associations in Chilean patients. A convenience sample of 37 cases of OCSCC (n=16) and OPSCC (n=21) was analyzed clinically (TNM, clinical stage) and histologically (WHO grade of differentiation, pattern of tumor invasion). We assessed the expression of p53, Ki67, HOXA1, HOXB7, type IV collagen (ColIV) and carcinoma-associated fibroblast (α-SMA-positive cells). Additionally we conducted a univariate/bivariate analysis to assess the relationship of these variables with survival rates. Males were mostly affected (56.2% OCSCC, 76.2% OPSCC). Patients were mainly diagnosed at III/IV clinical stages (68.8% OCSCC, 90.5% OPSCC) with a predominantly infiltrative pattern invasion (62.9% OCSCC, 57.1% OPSCC). Significant association between regional lymph nodes (N) and clinical stage with OCSCC-HOXB7 expression (Chi-Square test P < 0.05) was observed. In OPSCC a statistically significant association exists between p53, Ki67 with gender (Chi-Square test P < 0.05). In OCSCC and OPSCC was statistically significant association between ki67 with HOXA1, HOXB7, and between these last two antigens (Pearson's Correlation test P < 0.05). Furthermore OPSCC-p53 showed significant correlation when it was compared with α-SMA (Kendall's Tau-c test P < 0.05). Only OCSCC-pattern invasion and OPSCC-primary tumor (T) pattern resulted associated with survival at the end of the follow up period (Chi-Square Likelihood Ratio, P < 0.05). Clinical, histological and immunohistochemical features are similar to seen in other countries. Cancer proliferation markers were associated strongly from each other. Our sample highlights prognostic value of T and pattern of invasion, but the conclusions may be limited and should be considered with caution (small sample). Many cases were diagnosed in the advanced stages of the disease, which suggests that the diagnosis of OCSCC and OPSCC is made late.

The Use Of Medication And Associated Factors Among Adults Living In Campinas, São Paulo, Brazil: Differences Between Men And Women.

The objective of this study was to verify factors associated with the use of medication by adults, with emphasis on the differences between men and women. It was a population-based, cross-sectional study with cluster sampling conducted in two stages in Campinas in the state of São Paulo in 2008. Among the 2,413 individuals aged 20 or older, the prevalence of use of at least one drug in the three days before the research was 45.4% (95% CI: 41.3 - 49.4) in men and 64.6% (95% CI: 59.8 - 69.2) in women. For adult men over 40 years old who were not working, former smokers, with one or more chronic diseases, with two or more health problems and who sought health care or a health professional in the two weeks preceding the research showed higher prevalence of medication use. Among women, a higher prevalence of use was observed in females over 40, obese, former smokers, who reported a short sleep pattern, with one or more chronic diseases and two or more health problems, and who reported seeking a health care service or professional in the past 15 days. The findings showed some differences in the determinants of drug use in relation to gender, revealing the greater importance of health-related behavior among women.