Development of a Lab-on-a-Chip Device for Rapid Nanotoxicity Assessment In Vitro

Increasing useof nanomaterials in consumer products and biomedical applications creates the possibilities of intentional/unintentional exposure to humans and the environment. Beyond the physiological limit, the nanomaterialexposure to humans can induce toxicity. It is difficult to define toxicity of nanoparticles on humans as it varies by nanomaterialcomposition, size, surface properties and the target organ/cell line. Traditional tests for nanomaterialtoxicity assessment are mostly based on bulk-colorimetric assays. In many studies, nanomaterials have found to interfere with assay-dye to produce false results and usually require several hours or days to collect results. Therefore, there is a clear need for alternative tools that can provide accurate, rapid, and sensitive measure of initial nanomaterialscreening. Recent advancement in single cell studies has suggested discovering cell properties not found earlier in traditional bulk assays. A complex phenomenon, like nanotoxicity, may become clearer when studied at the single cell level, including with small colonies of cells. Advances in lab-on-a-chip techniques have played a significant role in drug discoveries and biosensor applications, however, rarely explored for nanomaterialtoxicity assessment. We presented such cell-integrated chip-based approach that provided quantitative and rapid response of cellhealth, through electrochemical measurements. Moreover, the novel design of the device presented in this study was capable of capturing and analyzing the cells at a single cell and small cell-population level. We examined the change in exocytosis (i.e. neurotransmitterrelease) properties of a single PC12 cell, when exposed to CuOand TiO2 nanoparticles. We found both nanomaterials to interfere with the cell exocytosis function. We also studied the whole-cell response of a single-cell and a small cell-population simultaneously in real-time for the first time. The presented study can be a reference to the future research in the direction of nanotoxicity assessment to develop miniature, simple, and cost-effective tool for fast, quantitative measurements at high throughput level. The designed lab-on-a-chip device and measurement techniques utilized in the present work can be applied for the assessment of othernanoparticles' toxicity, as well.

Development of hardware in the loop real-time control techniques for hybrid power systems involving distributed demands and sustainable energy sources

The future power grid will effectively utilize renewable energy resources and distributed generation to respond to energy demand while incorporating information technology and communication infrastructure for their optimum operation. This dissertation contributes to the development of real-time techniques, for wide-area monitoring and secure real-time control and operation of hybrid power systems. ^ To handle the increased level of real-time data exchange, this dissertation develops a supervisory control and data acquisition (SCADA) system that is equipped with a state estimation scheme from the real-time data. This system is verified on a specially developed laboratory-based test bed facility, as a hardware and software platform, to emulate the actual scenarios of a real hybrid power system with the highest level of similarities and capabilities to practical utility systems. It includes phasor measurements at hundreds of measurement points on the system. These measurements were obtained from especially developed laboratory based Phasor Measurement Unit (PMU) that is utilized in addition to existing commercially based PMU’s. The developed PMU was used in conjunction with the interconnected system along with the commercial PMU’s. The tested studies included a new technique for detecting the partially islanded micro grids in addition to several real-time techniques for synchronization and parameter identifications of hybrid systems. ^ Moreover, due to numerous integration of renewable energy resources through DC microgrids, this dissertation performs several practical cases for improvement of interoperability of such systems. Moreover, increased number of small and dispersed generating stations and their need to connect fast and properly into the AC grids, urged this work to explore the challenges that arise in synchronization of generators to the grid and through introduction of a Dynamic Brake system to improve the process of connecting distributed generators to the power grid.^ Real time operation and control requires data communication security. A research effort in this dissertation was developed based on Trusted Sensing Base (TSB) process for data communication security. The innovative TSB approach improves the security aspect of the power grid as a cyber-physical system. It is based on available GPS synchronization technology and provides protection against confidentiality attacks in critical power system infrastructures. ^

Hispanic orientalism: The literary development of a cultural paradigm, from medieval Spain to modern Latin America

This dissertation offers a novel approach to Hispanic Orientalism, developing a dynamic paradigm from its origins in medieval and Renaissance Iberia during the process of the Christian Reconquest, to its transatlantic migration and establishment in the early years of the Colony, from where it changed in late colonial and post-Independence Latin America, and onto modernity. ^ The study argues that Hispanic Orientalism does not necessarily imply a negative depiction of the Other, a quality associated with the traditional critique of Saidian Orientalism. Neither, does it entirely comply with the positivist approach suggested in the theoretical research of Said’s opponents, like Julia Kushigian. This dissertation also argues that sociopolitical changes and the shift in the discourse of powers, from imperial to non-imperial, had a significant impact of the development of Hispanic Orientalism, shaping the relationship with the Other. The methodology involves close reading of representative texts depicting the interactions of the dominant and dominated societies from each of the four historic periods that coincided with significant sociopolitical transformations in Hispanic society. Through an intercultural approach to literary studies, social history, and religious studies, this project develops an original paradigm of Hispanic Orientalism, derived from the image of the reinvented Semitic Other portrayed in the literary works depicting the relationship between the hegemonic and the subaltern cultures during the Reconquest period in Spain. Then, it traces the turn of the original paradigm towards reinterpretation during its transatlantic migration to Latin America through the analysis of the chronicles and travelogs of the first colonizers and explorers. During the transitional late colonial and early Independence periods Latin America sees a significant change in the discourse of powers, and Hispanic Orientalism reflects this oscillation between the past and the present therough the works of the Latin American authors from the seventeenth to the nineteenth centuries. Finally, once the non-imperial discourse of power established itself in the former Colony, a new modern stage in the development of Hispanic Orientalist paradigm takes place. It is marked by the desire to differentiate itself from the O(o)thers, as manifested in the works of the representatives of Modernism and the Boom.^

The development of an online neonatal intensive care unit family education

Background: British Columbia’s Fraser Health Authority (FHA) neonatal intensive care units (NICUs) value family centered care (FCC). Nevertheless, there is limited evidence that FCC is actually incorporated into practice, as well as some concern that FHA NICU education is inaccessible, inconsistent, or disorganized. Purpose: The mission of this project is to support the principles of FCC throughout the development of an FHA online NICU family education guide by reflecting upon the needs of families throughout their NICU journey. Methods: A needs assessment was initially completed and included literature reviews, consultations, and an environmental scan. This data informed development of an online NICU family education guide which plots current education materials along key stages of the NICU journey: prenatal, admission, early days, growing and developing, discharge and at home. For the purposes of this practicum, only the prenatal stage was fully developed and will serve as a template for other stages following a formative evaluation. A pamphlet and revised FHA Neonatal Checkpoint will also be developed to augment teaching by health care professionals. Implementation and evaluation plans were adapted from the Center for Disease Control Framework for Program Evaluation in Public Health. Results: The needs assessment validates and directs the development, implementation, and evaluation of the online guide illustrating an FCC approach. The online guide centralizes and organizes education by selecting education topics that relate to each stage of the NICU journey. This family-directed design enables families’ access to consistent and reliable information and offers them an opportunity to learn at their own pace. Conclusion: The process of creating, implementing, and evaluating an online family education program for FHA NICUs elucidates the intricacies and the advantages of integrating FCC into NICU practice.

Development of a triage tool for neurodevelopmental risk in children aged 30 months

Peer reviewed

Development of a triage tool for neurodevelopmental risk in children aged 30 months

Peer reviewed

Development of a program of radiopaque lesions images via radiographic cases for active learning in oral medicine

Through the creation of this project in English, we have made a file of radiographic images that will be used by third year dental students in order to improve the practical teaching part of the subject of Oral Medicine, essentially by incorporating these files to the Virtual Campus. We have selected the most representative radiopaque radiographic images studied in pathology lectures given. We have prepared a file with 59 radiopaque radiographic images. These lesions have been divided according to their relationship and number with the tooth, into the following groups: “Anatomic radiopacities”, “Periapical radiopacities”, “Solitary radiopacities not necessarily contacting teeth”,“Multiple separate radiopacities”, and “Generalized radiopacities”. We created 4 flowcharts synthesizing the mayor explanatory bases of each pathological process in relation to other pathologies within each location. We have focused primarily in those clinical and radiographic features that can help us differentiate one pathology from another. We believe that by giving the student a knowledge base through each flowchart, as well as provide clinical cases, will start their curiosity to seek new cases on the Internet or try to look for images that we have not been able to locate due to low frequency. In addition, as this project has been done in English, it will provide the students with necessary tools to do a literature search, as most of the medical and dental literature is in English; thus far, providing the student with this material necessary to make the appropriate searched using keywords in English.

Development of a triage tool for neurodevelopmental risk in children aged 30 months

Peer reviewed

The development of an automated nano sampling handling system for nanometne protein crystallography experiments

As the world's synchrotrons and X-FELs endeavour to meet the need to analyse ever-smaller protein crystals, there grows a requirement for a new technique to present nano-dimensional samples to the beam for X-ray diffraction experiments.The work presented here details developmental work to reconfigure the nano tweezer technology developed by Optofluidics (PA, USA) for the trapping of nano dimensional protein crystals for X-ray crystallography experiments. The system in its standard configuration is used to trap nano particles for optical microscopy. It uses silicon nitride laser waveguides that bridge a micro fluidic channel. These waveguides contain 180 nm apertures of enabling the system to use biologically compatible 1.6 micron wavelength laser light to trap nano dimensional biological samples. Using conventional laser tweezers, the wavelength required to trap such nano dimensional samples would destroy them. The system in its optical configuration has trapped protein molecules as small as 10 nanometres.

Development of a work-based learning MSc course which incorporates the development and demonstration of professional engineering competence standards

UK engineering standards are regulated by the Engineering Council (EC) using a set of generic threshold competence standards which all professionally registered Chartered Engineers in the UK must demonstrate, underpinned by a separate academic qualification at Masters Level. As part of an EC-led national project for the development of work-based learning (WBL) courses leading to Chartered Engineer registration, Aston University has started an MSc Professional Engineering programme, a development of a model originally designed by Kingston University, and build around a set of generic modules which map onto the competence standards. The learning pedagogy of these modules conforms to a widely recognised experiential learning model, with refinements incorporated from a number of other learning models. In particular, the use of workplace mentoring to support the development of critical reflection and to overcome barriers to learning is being incorporated into the learning space. This discussion paper explains the work that was done in collaboration with the EC and a number of Professional Engineering Institutions, to design a course structure and curricular framework that optimises the engineering learning process for engineers already working across a wide range of industries, and to address issues of engineering sustainability. It also explains the thinking behind the work that has been started to provide an international version of the course, built around a set of globalised engineering competences. © 2010 W J Glew, E F Elsworth.

The development of a semantic model for the interpretation of mathematics including the use of technology

The semantic model developed in this research was in response to the difficulty a group of mathematics learners had with conventional mathematical language and their interpretation of mathematical constructs. In order to develop the model ideas from linguistics, psycholinguistics, cognitive psychology, formal languages and natural language processing were investigated. This investigation led to the identification of four main processes: the parsing process, syntactic processing, semantic processing and conceptual processing. The model showed the complex interdependency between these four processes and provided a theoretical framework in which the behaviour of the mathematics learner could be analysed. The model was then extended to include the use of technological artefacts into the learning process. To facilitate this aspect of the research, the theory of instrumentation was incorporated into the semantic model. The conclusion of this research was that although the cognitive processes were interdependent, they could develop at different rates until mastery of a topic was achieved. It also found that the introduction of a technological artefact into the learning environment introduced another layer of complexity, both in terms of the learning process and the underlying relationship between the four cognitive processes.

Role of Hydrological Process Representation on Erosion, Deposition, and Sediment Yield Estimate

Soil erosion by water is a major driven force causing land degradation. Laboratory experiments, on-site field study, and suspended sediments measurements were major fundamental approaches to study the mechanisms of soil water erosion and to quantify the erosive losses during rain events. The experimental research faces the challenge to extent the result to a wider spatial scale. Soil water erosion modeling provides possible solutions for scaling problems in erosion research, and is of principal importance to better understanding the governing processes of water erosion. However, soil water erosion models were considered to have limited value in practice. Uncertainties in hydrological simulations are among the reasons that hindering the development of water erosion model. Hydrological models gained substantial improvement recently and several water erosion models took advantages of the improvement of hydrological models. It is crucial to know the impact of changes in hydrological processes modeling on soil erosion simulation.

This dissertation work first created an erosion modeling tool (GEOtopSed) that takes advantage of the comprehensive hydrological model (GEOtop). The newly created tool was then tested and evaluated at an experimental watershed. The GEOtopSed model showed its ability to estimate multi-year soil erosion rate with varied hydrological conditions. To investigate the impact of different hydrological representations on soil erosion simulation, a 11-year simulation experiment was conducted for six models with varied configurations. The results were compared at varied temporal and spatial scales to highlight the roles of hydrological feedbacks on erosion. Models with simplified hydrological representations showed agreement with GEOtopSed model on long temporal scale (longer than annual). This result led to an investigation for erosion simulation at different rainfall regimes to check whether models with different hydrological representations have agreement on the soil water erosion responses to the changing climate. Multi-year ensemble simulations with different extreme precipitation scenarios were conducted at seven climate regions. The differences in erosion simulation results showed the influences of hydrological feedbacks which cannot be seen by purely rainfall erosivity method.

Non-Pharmacological Approaches for Pain Management in Sickle Cell Disease: Development of a Mindfulness-Based Intervention

Background: Sickle Cell Disease (SCD) is a genetic hematological disorder that affects more than 7 million people globally (NHLBI, 2009). It is estimated that 50% of adults with SCD experience pain on most days, with 1/3 experiencing chronic pain daily (Smith et al., 2008). Persons with SCD also experience higher levels of pain catastrophizing (feelings of helplessness, pain rumination and magnification) than other chronic pain conditions, which is associated with increases in pain intensity, pain behavior, analgesic consumption, frequency and duration of hospital visits, and with reduced daily activities (Sullivan, Bishop, & Pivik, 1995; Keefe et al., 2000; Gil et al., 1992 & 1993). Therefore effective interventions are needed that can successfully be used manage pain and pain-related outcomes (e.g., pain catastrophizing) in persons with SCD. A review of the literature demonstrated limited information regarding the feasibility and efficacy of non-pharmacological approaches for pain in persons with SCD, finding an average effect size of .33 on pain reduction across measurable non-pharmacological studies. Second, a prospective study on persons with SCD that received care for a vaso-occlusive crisis (VOC; N = 95) found: (1) high levels of patient reported depression (29%) and anxiety (34%), and (2) that unemployment was significantly associated with increased frequency of acute care encounters and hospital admissions per person. Research suggests that one promising category of non-pharmacological interventions for managing both physical and affective components of pain are Mindfulness-based Interventions (MBIs; Thompson et al., 2010; Cox et al., 2013). The primary goal of this dissertation was thus to develop and test the feasibility, acceptability, and efficacy of a telephonic MBI for pain catastrophizing in persons with SCD and chronic pain.

Methods: First, a telephonic MBI was developed through an informal process that involved iterative feedback from patients, clinical experts in SCD and pain management, social workers, psychologists, and mindfulness clinicians. Through this process, relevant topics and skills were selected to adapt in each MBI session. Second, a pilot randomized controlled trial was conducted to test the feasibility, acceptability, and efficacy of the telephonic MBI for pain catastrophizing in persons with SCD and chronic pain. Acceptability and feasibility were determined by assessment of recruitment, attrition, dropout, and refusal rates (including refusal reasons), along with semi-structured interviews with nine randomly selected patients at the end of study. Participants completed assessments at baseline, Week 1, 3, and 6 to assess efficacy of the intervention on decreasing pain catastrophizing and other pain-related outcomes.

Results: A telephonic MBI is feasible and acceptable for persons with SCD and chronic pain. Seventy-eight patients with SCD and chronic pain were approached, and 76% (N = 60) were enrolled and randomized. The MBI attendance rate, approximately 57% of participants completing at least four mindfulness sessions, was deemed acceptable, and participants that received the telephonic MBI described it as acceptable, easy to access, and consume in post-intervention interviews. The amount of missing data was undesirable (MBI condition, 40%; control condition, 25%), but fell within the range of expected missing outcome data for a RCT with multiple follow-up assessments. Efficacy of the MBI on pain catastrophizing could not be determined due to small sample size and degree of missing data, but trajectory analyses conducted for the MBI condition only trended in the right direction and pain catastrophizing approached statistically significance.

Conclusion: Overall results showed that at telephonic group-based MBI is acceptable and feasible for persons with SCD and chronic pain. Though the study was not able to determine treatment efficacy nor powered to detect a statistically significant difference between conditions, participants (1) described the intervention as acceptable, and (2) the observed effect sizes for the MBI condition demonstrated large effects of the MBI on pain catastrophizing, mental health, and physical health. Replication of this MBI study with a larger sample size, active control group, and additional assessments at the end of each week (e.g., Week 1 through Week 6) is needed to determine treatment efficacy. Many lessons were learned that will guide the development of future studies including which MBI strategies were most helpful, methods to encourage continued participation, and how to improve data capture.

Development of Plasmonic Nanoplatforms for Diagnostics, Therapy, and Sensing

Recent advances in nanotechnology have led to the application of nanoparticles in a wide variety of fields. In the field of nanomedicine, there is great emphasis on combining diagnostic and therapeutic modalities into a single nanoparticle construct (theranostics). In particular, anisotropic nanoparticles have shown great potential for surface-enhanced Raman scattering (SERS) detection due to their unique optical properties. Gold nanostars are a type of anisotropic nanoparticle with one of the highest SERS enhancement factors in a non-aggregated state. By utilizing the distinct characteristics of gold nanostars, new plasmonic materials for diagnostics, therapy, and sensing can be synthesized. The work described herein is divided into two main themes. The first half presents a novel, theranostic nanoplatform that can be used for both SERS detection and photodynamic therapy (PDT). The second half involves the rational design of silver-coated gold nanostars for increasing SERS signal intensity and improving reproducibility and quantification in SERS measurements.

The theranostic nanoplatforms consist of Raman-labeled gold nanostars coated with a silica shell. Photosensitizer molecules for PDT can be loaded into the silica matrix, while retaining the SERS signal of the gold nanostar core. SERS detection and PDT are performed at different wavelengths, so there is no interference between the diagnostic and therapeutic modalities. Singlet oxygen generation (a measure of PDT effectiveness) was demonstrated from the drug-loaded nanocomposites. In vitro testing with breast cancer cells showed that the nanoplatform could be successfully used for PDT. When further conjugating the nanoplatform with a cell-penetrating peptide (CPP), efficacy of both SERS detection and PDT is enhanced.

The rational design of plasmonic nanoparticles for SERS sensing involved the synthesis of silver-coated gold nanostars. Investigation of the silver coating process revealed that preservation of the gold nanostar tips was necessary to achieve the increased SERS intensity. At the optimal amount of silver coating, the SERS intensity is increased by over an order of magnitude. It was determined that a majority of the increased SERS signal can be attributed to reducing the inner filter effect, as the silver coating process moves the extinction of the particles far away from the laser excitation line. To improve reproducibility and quantitative SERS detection, an internal standard was incorporated into the particles. By embedding a small-molecule dye between the gold and silver surfaces, SERS signal was obtained both from the internal dye and external analyte on the particle surface. By normalizing the external analyte signal to the internal reference signal, reproducibility and quantitative analysis are improved in a variety of experimental conditions.

Market-oriented new product development of health promoting foods for the ageing population

Major factors influencing food development and food marketing strategies in global market places at present can be attributable to the changing age structure of the population. The significant shifts in global age structure will inevitably lead to the number of people aged 60 reaching an all-time high of one billion by the year 2020. The rapidly growing population of ageing people globally represents a large, neglected and very much under-developed category within the Food Industry. The primary focus of this study was the integration of knowledge creation techniques at early NPD stages, for the development of market-oriented new health promoting foods for the ageing population. The methodology of this study was centered on an exploratory sequential mixed methods strategy. Stage one of the study involved in-depth semi-structured interviews with 16 Stakeholders to facilitate the need identification stage of the NPD process. The main outputs identified were the need for: the fortification of foods for a preventative nutrition approach, the development of foods that targeted age-related conditions such as cognitive, heart, gut and bone health, the integration of ageing compensatory packaging adaptations and the creation of marketing messages with an active lifestyle message. Stage two consisted of a market-oriented computer assisted NPD technique, a user centered design interaction (UCD) to integrate consumers as co-creators throughout the idea generation stage of the NPD process. The most important product attributes identified in this stage included: products targeted at brain and cognitive health, liquid based beverages, easy to use packaging with environmentally friendly elements, simplistic marketing with a clear focus on health not age and realistic health claims constructed with consumer friendly terminology. Finally, Stage three used an abbreviated means-end chain (MEC) analysis to complete the concept development stage of the NPD process. This stage identified commercial information that could be used by food firms for the development of positioning and communication strategies. Equally, the information generated could be of high strategic importance to governments, policy makers, health professionals and medical professionals. The values and goals listed in this stage included: better overall health, active lifestyle, optimum nutrition and wellbeing feelings. Overall, this research illustrated that knowledge creation techniques can assist firms in the development of market-oriented health promoting foods for the ageing population.