Toward a Theory of Multi-Method Modeling and Simulation Approach

The representation via simulation models can easily lead to simulation models too simple for their intended purpose, or with too much detail, making them hard to understand. This problem is related to limitations of the modeling and simulation methods. A multi-method Modeling and Simulation (M&S) approach has the potential for improved representation by taking advantage of methods\u27 strengths and mitigating their weaknesses. Despite a high appeal for using multiple M&S methods, several related problems should be addressed first. The current level of theoretical, methodological, and pragmatic knowledge related to a multi-method M&S approach is limited. It is problematic that there is no clearly identified purpose and definition of the multi-method M&S approach. Theoretical and methodological advances are vital to enhancing the application of a multi-method M&S approach to address a broader range of scientific inquiries, improve quality of research, and enable finding common ground between scientific domains. This dissertation explored theoretical principles and research guidelines of a multi-method M&S approach. The analyzed literature offered perspectives related to the purpose, terms, and research guidelines of a multi-method M&S approach. A pragmatic philosophical stance was used to provide the basis for the choice of terms and definitions relevant to a multi-method M&S approach were proposed. The degrees of falsifiability are adapted to the M&S domain, which allowed for developing complementarity principles as the theoretical basis of a multi-method M&S approach. Next, a blueprint of a multi-method M&S approach called method formats was derived, because transitions toward formats must seek justifications in order to increase research objectivity and transparency. A sample set of methods was explored in the context of a proposed sample set of criteria. None of the methods were evaluated with the maximum score for every criterion, which implied that if all those characteristics were required within a research context, then, none of the methods could provide the highest possible score without combining methods. Finally, a case study that included a multi-method simulation model was developed, providing a data layer for evaluation of complementarity principles. The case study contributed to the credibility of complementarity principles as a reason to use a multi-method M&S approach and value of pseudo-triangulation as a mean of verification of a selected approach

Light Sterile Neutrinos: A White Paper

This white paper addresses the hypothesis of light sterile neutrinos based on recent anomalies observed in neutrino experiments and the latest astrophysical data

New Perspectives on Implementing Health Information Technology

The importance of studying challenges in implementing information technology solutions in health care organizations is highlighted by the huge investments in health care information technology (HIT) which has been spurred by recent government mandates. Information technology can help improve health care delivery cost by facilitating the standardization of work processes or routines and reducing variations among them. Set in a premier 950+ bed hospital in the south eastern part of US, this dissertation consists of two studies examining the challenges involved in implementing HIT solutions. In the first study, we seek to gain deep insights into how the process of creating a patient’s chart evolves over time in a health care institution. The second study focuses on the users of Electronic Health Records (EHR) system, investigating the compliance behavior of various providers with respect to patient records in the system. In the first study, through the lens of Activity theory our results show that the charting routine is implicated by the following environmental factors: (1) Tools, (2) Rules, (3) Community, and (4) Roles, and by individual factors: (5) Computer Self-Efficacy and (6) Risk Propensity. In the second study, our results indicate that there is a substantial effect of subculture of the different occupational groups on IT security compliance intent and behavior in a health care institution

Mapping the relationship between curriculum, pedagogy and digital technology to develop a predictive model for the improvement in students' attainment

The relationship between learning, pedagogy and technology is a complex area of injury. Working with, and analysing data generated by, twenty teachers and two hundred seventy-eight students from the Institute of Applied Technology (IAT) in the United Arab Emirates, I was able to drill down into the complex interactions between curriculum, pedagogy and technology. From this work, I developed an original predictive model, which outlines the improvement in students' attainment due to the complex interactions of three critical elements - curriculum (C), pedagogy (P), and digital technology (T), what I call the CPT model. My analysis indicated that digital technology impacted positively on students' attainment when it was used with science subjects but less so when it was used with humanities subjects. Based on the literature review, the relationship between C, P and T had been widely investigated (see, for example, Mishra and Koehler (2006; 2013), Archambault and Barnett (2010), Angeli and Valanides (2009), Voogt et al. (2012)). However, none of the researchers dealt with this relationship and its impact on students' learning and attainment quantitatively or using a mathematical perspective. This study aims to highlight how the CPT model can predict the improvement in students' attainment as an outcome of using educational technology (the impact factor) and locate the most effective strategies of learning. This research fills the knowledge gap by developing a new model that explores the C, P, T correlations using three-dimensional equations that I have developed. As such, the study makes a significant contribution to educational technology literature through exploring the C, P, T impact on students' attainment. The research offers educators, policymakers and curriculum developers opportunities to leverage digital technology as a mean for enhancing attainment. Understanding the CPT relationship enables the development of focussed digital technology-supported curricular for students regardless of their academic level. I concluded this by arguing that the CPT model can guide both teachers and policymakers to locate the most effective strategy of learning to maximise the impact of digital technology on students' attainment. This PhD study contributes to knowledge by a new educational term called Tranology, which is a combination of two main types of learning, traditional and digital technology-based learning, please refer to sections 2.9 and 8.4. Furthermore, this study suggests the application of the vector space concept to organise the relationship between the elements C, P and T. In turn, this implies that these elements overlap over three-dimensional space, which is addressed in this study as the CPT space, rather than, overlapping over two-dimensional plane as demonstrated by Mishra and Koehler (2005; 2006; 2008), please refer to chapter 5. In terms of future scientific understanding and theoretical insights, the CPT model can be transformed from three-dimensional model (C, P and T) to four-dimensional model (4-D) that comprises the three dimensions of curriculum, pedagogy and digital technology (C, P and T) and the one dimension of a student's attitude towards learning (S) to produce 4-D model called the CPT-S curvatures. Please refer to section 8.6

Multidisciplinary Pain management: Psychosocial Outcomes and Effect on Neurophysiological Responses to Pain

Background: The efficacy of UK National Health Service (NHS) multidisciplinary pain management programmes (PMPs) is currently measured using self-report questionnaires. Whilst subjective measurements provide important information about personal experiences, they cannot reveal underlying changes in cortical activity related to pain that may also accompany PMP treatment. There is no objective measurement of treatment efficacy currently available. This thesis contains studies of two NHS PMPs that differ in their psychological approach. The effect of these treatments was assessed using self-report questionnaire measures, and a newly developed neurophysiological assessment technique. Methods: Studies examined the effect of a cognitive-behavioural therapy (CBT) based PMP, and an acceptance and commitment therapy (ACT) based PMP, upon questionnaire measures of psychological, physical, and social health, as well as measures of coping and acceptance. Further studies examined pre- to post-treatment changes in patients’ cortical pain processing measured using electroencephalography (EEG), as well as in healthy and patient (waiting list/treatment as usual) control groups. The effect of treatment on contact heat evoked potentials (CHEPs), and on changes in power spectral density (PSD) following exposure to medium duration tonic pain (90s cold pressor test) was investigated. Results: Small but significant (p<.05) improvements in self-report measures of mental health, coping, and acceptance were found in patients following both CBT- and ACT-based PMPs. There were differences in the effect of PMPs on measures of anxiety, depression and catastrophising, with the ACT-based programme data showing slightly larger effect sizes. Neurophysiological testing revealed no pattern of effect upon CHEPs, however there were pre- to post-treatment differences in the effect of tonic pain upon PSD. Alpha (α) and theta (θ) rhythms were significantly (p<.05) reduced pre-treatment in the CBT group (n=12); post-treatment this effect was not iv observed. There were no pre- to post-treatment differences in the ACT group (n=4) and there were also no changes in either healthy (n=14) or waiting list (n=13) control groups between test sessions. Conclusion: Both PMPs studied brought about small but significant improvements in patients’ perceived mental and physical health. Despite their differences both programmes were clinically beneficial to patients in terms of self-report measures. Measurable change was observed in the cortical response to pain pre- to post-treatment with a CBT-based PMP, most likely due to a change in cognitive appraisal of painful signals brought about by taking part in the PMP. Results imply the possible use of neurophysiological assessment to identify patients who may benefit most from treatment, to match treatments to patients’ individual psychological and neurophysiological profile, and to more closely monitor treatment efficacy

2019-2020 Lindenwood University Accelerated Degree Program Course Catalog

Lindenwood University Accelerated Degree Program Course Cataloghttps://digitalcommons.lindenwood.edu/catalogs/1188/thumbnail.jp

Identification and Characterization of Modulators of Human MRP1 (ABCC1) and Human MRP2 (ABCC2) Expression

ATP-binding cassette (ABC) transporters are known to play a critical role in conferring multidrug resistance (MDR) in various cancers. Several retrospective analyses of chemotherapy results have reported high expression of Multidrug Resistance Protein 1 (MRP1) and Multidrug Resistance Protein 2 (MRP2) in tumor cells exhibiting the MDR phenotype. High MRP1 and MRP2 expression in cancer patients predict a higher risk of treatment failure, resulting in relapse and disease recurrence as well as shortened survival rates. The key role of MRP1 and MRP2 play in the development of MDR makes them important therapeutic targets that hold a great promise for addressing multidrug resistance in cancer cells. Since MRP1 and MRP2 play critical roles in the regulation of various cellular pathways by altering the levels of several key signaling molecules, finding ways of modulating the activities and expression of these transporters in cancer cells is of great clinical interest in oncology research. We identified four novel modulators of MRP1 from our initial screening of 30 therapeutic compounds using an In-Cell ELISA assay. Three of these compounds; Amuvatinib, SB743921 HCl, TG101348 (SAR302503), which were identified to be ATP competitive inhibitors based on their mode of action, decreased MRP1 expression whereas Felbamate (a recently approved FDA drug) increased MRP1 protein expression. Our findings revealed that these ATP competitive inhibitors decreased MRP1- mediated calcein accumulation. These compounds inhibited the growth of HEK293 MRP1-overexpressing cells at clinically achievable concentrations, and also reversed MRP1- mediated resistance in these cells. Since regulation of the activity of activators and effectors of specific biochemical pathways provide a means of regulating downstream signaling, we investigated the effect of a novel Tie2 kinase inhibitor and mTOR inhibitor, Everolimus, on MRP1 activity and expression. Tie2 is an activator of the PI3K/Akt pathway (a pathway known to modulate MRP1 activity and expression) whereas mTOR is a downstream effector of this pathway. We demonstrated using a flow cytometry-based calcein accumulation assay, and MTT based reversal resistance studies that Tie2 kinase inhibitor and Everolimus can decrease MRP1 mediated calcein efflux and reverse MRP1 mediated resistance towards vincristine in HEK293 MRP1-overexpressing cells. Lastly, we identified 49 modulators of MRP2 from our initial screening of 372 FDA-approved drugs from a recently approved FDA drug library representing 13.17% of total compounds screened. Thirty-nine (39) drugs increased MRP2 expression whereas 10 drugs lowered expression of MRP2 after drug treatment. Results from this screening reaffirm the promiscuous nature of the MRP2 transporter, and how important it is to investigate the interaction between both old and newly developed drugs with MRP2. The modulators identified from this study would be further characterized in future projects. Overall, our findings signify the importance of profiling drug interactions with these transporters, and the data obtained would provide essential information to improve combinatorial drug therapy and precision medicine as well as reduce drug toxicity of various cancer chemotherapies