Search results for: Jared Warren
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 31

Search results for: Jared Warren

31 Evaluation and Comparison of Seismic Performance of Structural Trusses under Cyclic Loading with Finite Element Method

Authors: Masoud Mahdavi

Abstract:

The structure is made using different members and combining them with each other. These members are basically based on technical and engineering principles and are combined in different ways and have their own unique effects on the building. Trusses are one of the most common and important members of the structure, accounting for a large percentage of the power transmission structure in the building. Different types of trusses are based on structural needs and evaluating and making complete comparisons between them is one of the most important engineering analyses. In the present study, four types of trusses have been studied; 1) Hawe truss, 2) Pratt truss, 3) k truss, and 4) warren truss, under cyclic loading for 80 seconds. The trusses are modeled in 3d using st37 steel. The results showed that Hawe trusses had higher values ​​than all other trusses (k, Pratt and Warren) in all the studied indicators. Indicators examined in the study include; 1) von Mises stresses, 2) displacement, 3) support force, 4) velocity, 5) acceleration, 6) capacity (hysteresis curve) and 7) energy diagram. Pratt truss in indicators; Mises stress, displacement, energy have the least amount compared to other trusses. K truss in indicators; support force, speed and acceleration are the lowest compared to other trusses.

Keywords: hawe truss, pratt truss, K truss, warren truss, cyclic loading, finite element method

Procedia PDF Downloads 144
30 Mobile Application Interventions in Positive Psychology: Current Status and Recommendations for Effective App Design

Authors: Gus Salazar, Jeremy Bekker, Lauren Linford, Jared Warren

Abstract:

Positive psychology practices allow for its principles to be applied to all people, regardless of their current level of functioning. To increase the dissemination of these practices, interventions are being adapted for use with digital technology, such as mobile apps. However, the research regarding positive psychology mobile app interventions is still in its infancy. In an effort to facilitate progress in this important area, we 1) conducted a qualitative review to summarize the current state of the positive psychology mobile app literature and 2) developed research-supported recommendations for positive psychology app development to maximize behavior change. In our literature review, we found that while positive psychology apps varied widely in content and purpose, there was a near-complete lack of research supporting their effectiveness. Most apps provided no rationale for the behavioral change techniques (BCTs) they employed in their app, and most did not develop their app with specific theoretical frameworks or design models in mind. Given this problem, we recommended four steps for effective positive psychology app design. First, developers must establish their app in a research-supported theory of change. Second, researchers must select appropriate behavioral change techniques which are consistent with their app’s goals. Third, researchers must leverage effective design principles. These steps will help mobile applications use data-driven methods for encouraging behavior change in their users. Lastly, we discuss directions for future research. In particular, researchers must investigate the effectiveness of various BCTs in positive psychology interventions. Although there is some research on this point, we do not yet clearly understand the mechanisms within the apps that lead to behavior change. Additionally, app developers must also provide data on the effectiveness of their mobile apps. As developers follow these steps for effective app development and as researchers continue to investigate what makes these apps most effective, we will provide millions of people in need with access to research-based mental health resources.

Keywords: behavioral change techniques, mobile app, mobile intervention, positive psychology

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29 Psychometric Properties of Several New Positive Psychology Measures

Authors: Lauren Benyo Linford, Jared Warren, Jeremy Bekker, Gus Salazar

Abstract:

In order to accurately identify areas needing improvement and track growth, the availability of valid and reliable measures of different facets of well-being is vital. Because no specific measures currently exist for many facets of well-being, the purpose of this study was to construct and validate measures of the following constructs: Purpose, Values, Mindfulness, Savoring, Gratitude, Optimism, Supportive Relationships, Interconnectedness, Compassion, Community, Contribution, Engaged Living, Personal Growth, Flow Experiences, Self-Compassion, Exercise, Meditation, and an overall measure of subjective well-being—the Survey on Flourishing. In order to assess their psychometric properties, each measure was examined for internal consistency estimates, and items with poor item-test correlations were dropped. Additionally, the convergent validity of the Survey on Flourishing (SURF) was assessed. Total score correlations of SURF and other commonly used measures of well-being such as the Positive and Negative Affect Schedule (PANAS), The Satisfaction with Life Scale (SWLS), the PERMA Profiler (measure of Positive Emotion, Engagement, Relationships, Meaning, and Achievement) were examined to establish convergent validity. The Kessler Psychological distress scale (K6) was also included to determine the divergent validity of the SURF measure. Three week test-retest reliability was also assessed for the SURF measure. Additionally, normative data from general population samples was collected for both the Self-Compassion and Survey on Flourishing (SURF) measures. The purpose of this study is to introduce each of these measures, divulge the psychometric findings of this study, as well as explore additional psychometric properties of the SURF measure in particular. This study will highlight how these measures can be used in future research exploring these positive psychology constructs. Additionally, this study will discuss the utility of these measures to guide individuals in their use of the online self-directed, self-administered My Best Self 101 positive psychology resources developed by the researchers. The goal of My Best Self 101 is to disseminate real, research-based measures and tools to individuals who are seeking to increase their well-being.

Keywords: measurement, psychometrics, test validation, well-Being

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28 A Middleware Management System with Supporting Holonic Modules for Reconfigurable Management System

Authors: Roscoe McLean, Jared Padayachee, Glen Bright

Abstract:

There is currently a gap in the technology covering the rapid establishment of control after a reconfiguration in a Reconfigurable Manufacturing System. This gap involves the detection of the factory floor state and the communication link between the factory floor and the high-level software. In this paper, a thin, hardware-supported Middleware Management System (MMS) is proposed and its design and implementation are discussed. The research found that a cost-effective localization technique can be combined with intelligent software to speed up the ramp-up of a reconfigured system. The MMS makes the process more intelligent, more efficient and less time-consuming, thus supporting the industrial implementation of the RMS paradigm.

Keywords: intelligent systems, middleware, reconfigurable manufacturing, management system

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27 Primes as Sums and Differences of Two Binomial Coefficients and Two Powersums

Authors: Benjamin Lee Warren

Abstract:

Many problems exist in additive number theory which is essential to determine the primes that are the sum of two elements from a given single-variable polynomial sequence, and most of them are unattackable in the present day. Here, we determine solutions for this problem to a few certain sequences (certain binomial coefficients and power sums) using only elementary algebra and some algebraic factoring methods (as well as Euclid’s Lemma and Faulhaber’s Formula). In particular, we show that there are finitely many primes as sums of two of these types of elements. Several cases are fully illustrated, and bounds are presented for the cases not fully illustrated.

Keywords: binomial coefficients, power sums, primes, algebra

Procedia PDF Downloads 102
26 Disseminating Positive Psychology Resources Online: Current Research and Future Directions

Authors: Warren Jared, Bekker Jeremy, Salazar Guy, Jackman Katelyn, Linford Lauren

Abstract:

Introduction: Positive Psychology research has burgeoned in the past 20 years; however, relatively few evidence-based resources to cultivate positive psychology skills are widely available to the general public. The positive psychology resources at www.mybestself101.org were developed to assist individuals in cultivating well-being using a variety of techniques, including gratitude, purpose, mindfulness, self-compassion, savoring, personal growth, and supportive relationships. These resources are empirically based and are built to be accessible to a broad audience. Key Objectives: This presentation highlights results from two recent randomized intervention studies of specific MBS101 learning modules. A key objective of this research is to empirically assess the efficacy and usability of these online resources. Another objective of this research is to encourage the broad dissemination of online positive psychology resources; thus, recommendations for further research and dissemination will be discussed. Methods: In both interventions, we recruited adult participants using social media advertisements. The participants completed several well-being and positive psychology construct-specific measures (savoring and self-compassion measures) at baseline and post-intervention. Participants in the experimental condition were also given a feedback questionnaire to gather qualitative data on how participants viewed the modules. Participants in the self-compassion study were randomly split between an experimental group, who received the treatment, and a control group, who were placed on a waitlist. There was no control group for the savoring study. Participants were instructed to read content on the module and practice savoring or self-compassion strategies listed in the module for a minimum of twenty minutes a day for 21 days. The intervention was semi-structured, as participants were free to choose which module activities they would complete from a menu of research-based strategies. Participants tracked which activities they completed and how long they spent on the modules each day. Results: In the savoring study, participants increased in savoring ability as indicated by multiple measures. In addition, participants increased in well-being from pre- to post-treatment. In the self-compassion study, repeated measures mixed model analyses revealed that compared to waitlist controls, participants who used the MBS101 self-compassion module experienced significant improvements in self-compassion, well-being, and body image with effect sizes ranging from medium to large. Attrition was 10.5% for the self-compassion study and 71% for the savoring study. Overall, participants indicated that the modules were generally helpful, and they particularly appreciated the specific strategy menus. Participants requested more structured course activities, more interactive content, and more practice activities overall. Recommendations: Mybestself101.org is an applied positive psychology research program that shows promise as a model for effectively disseminating evidence-based positive psychology resources that are both engaging and easily accessible. Considerable research is still needed, both to test the efficacy and usability of the modules currently available and to improve them based on participant feedback. Feedback received from participants in the randomized controlled trial led to the development of an expanded, 30-day online course called The Gift of Self-Compassion and an online mindfulness course currently in development called Mindfulness For Humans.

Keywords: positive psychology, intervention, online resources, self-compassion, dissemination, online curriculum

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25 Education for Social Justice: University Teachers’ Conceptions and Practice: A Comparative Study

Authors: Digby Warren, Jiri Kropac

Abstract:

While aspirations of social justice are often articulated by universities as a “feel good” mantra, what is meant by education for social justice deserves deeper consideration. Based on in-depth interviews with academics (voluntary participants in this research) in different disciplines and institutions in the UK, Czech Republic, and other EU countries, this comparative study presents thematic findings regarding lecturers’ conceptions of education for social justice -what it is, why it is important, why they are personally committed to it, how it connects with their own values- and their practice of it- how it is implemented through curriculum content, teaching and learning activities, and assessment tasks. It concludes by presenting an analysis of the challenges, constraints, and enabling factors in practising social justice education in different subject, institutional and national contexts.

Keywords: higher education, social justice, inclusivity, diversity

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24 Metastatic Polypoid Nodular Melanoma Management During The COVID-19 Pandemic

Authors: Stefan Bradu, Daniel Siegel, Jameson Loyal, Andrea Leaf, Alana Kurtti, Usha Alapati, Jared Jagdeo

Abstract:

Compared with all other variants of nodular melanoma, patients with polypoid nodular melanoma have the lowest 5-year survival rate. The pathophysiology and management of polypoid melanoma are scarcely reported in the literature. Although surgical excision is the cornerstone of melanoma management, treatment of polypoid melanoma is complicated by several negative prognostic factors, including early metastasis. This report demonstrates the successful treatment of a rapidly developing red nodular polypoid melanoma with metastasis using surgery and adjuvant nivolumab in a SARS-CoV-2-positive patient who delayed seeking care due to the COVID-19 pandemic. In addition to detailing the successful treatment approach, the immunosuppressive effects of SARS-2-CoV and its possible contribution to the rapid progression of polypoid melanoma are discussed. This case highlights the complex challenges of melanoma diagnosis and management during the COVID-19 pandemic.

Keywords: covid-19, dermatology, immunotherapy, melanoma, nivolumab

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23 VANETs: Security Challenges and Future Directions

Authors: Jared Oluoch

Abstract:

Connected vehicles are equipped with wireless sensors that aid in Vehicle to Vehicle (V2V) and Vehicle to Infrastructure (V2I) communication. These vehicles will in the near future provide road safety, improve transport efficiency, and reduce traffic congestion. One of the challenges for connected vehicles is how to ensure that information sent across the network is secure. If security of the network is not guaranteed, several attacks can occur, thereby compromising the robustness, reliability, and efficiency of the network. This paper discusses existing security mechanisms and unique properties of connected vehicles. The methodology employed in this work is exploratory. The paper reviews existing security solutions for connected vehicles. More concretely, it discusses various cryptographic mechanisms available, and suggests areas of improvement. The study proposes a combination of symmetric key encryption and public key cryptography to improve security. The study further proposes message aggregation as a technique to overcome message redundancy. This paper offers a comprehensive overview of connected vehicles technology, its applications, its security mechanisms, open challenges, and potential areas of future research.

Keywords: VANET, connected vehicles, 802.11p, WAVE, DSRC, trust, security, cryptography

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22 Overall Student Satisfaction at Tabor School of Education: An Examination of Key Factors Based on the AUSSE SEQ

Authors: Francisco Ben, Tracey Price, Chad Morrison, Victoria Warren, Willy Gollan, Robyn Dunbar, Frank Davies, Mark Sorrell

Abstract:

This paper focuses particularly on the educational aspects that contribute to the overall educational satisfaction rated by Tabor School of Education students who participated in the Australasian Survey of Student Engagement (AUSSE) conducted by the Australian Council for Educational Research (ACER) in 2010, 2012 and 2013. In all three years of participation, Tabor ranked first especially in the area of overall student satisfaction. By using a single level path analysis in relation to the AUSSE datasets collected using the Student Engagement Questionnaire (SEQ) for Tabor School of Education, seven aspects that contribute to overall student satisfaction have been identified. There appears to be a direct causal link between aspects of the Supportive Learning Environment, Work Integrated Learning, Career Readiness, Academic Challenge, and overall educational satisfaction levels. A further three aspects, being Student and Staff Interactions, Active Learning, and Enriching Educational Experiences, indirectly influence overall educational satisfaction levels.

Keywords: attrition, retention, educational experience, pre-service teacher education, student satisfaction

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21 Cyber Security Enhancement via Software Defined Pseudo-Random Private IP Address Hopping

Authors: Andre Slonopas, Zona Kostic, Warren Thompson

Abstract:

Obfuscation is one of the most useful tools to prevent network compromise. Previous research focused on the obfuscation of the network communications between external-facing edge devices. This work proposes the use of two edge devices, external and internal facing, which communicate via private IPv4 addresses in a software-defined pseudo-random IP hopping. This methodology does not require additional IP addresses and/or resources to implement. Statistical analyses demonstrate that the hopping surface must be at least 1e3 IP addresses in size with a broad standard deviation to minimize the possibility of coincidence of monitored and communication IPs. The probability of breaking the hopping algorithm requires a collection of at least 1e6 samples, which for large hopping surfaces will take years to collect. The probability of dropped packets is controlled via memory buffers and the frequency of hops and can be reduced to levels acceptable for video streaming. This methodology provides an impenetrable layer of security ideal for information and supervisory control and data acquisition systems.

Keywords: moving target defense, cybersecurity, network security, hopping randomization, software defined network, network security theory

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20 Education For Social Justice: A Comparative Study of University Teachers' Conceptions and Practice

Authors: Digby Warren, Jiri Kropac

Abstract:

This comparative study seeks to develop a deeper understanding of what is meant by “education for social justice” (ESJ) - an aspiration articulated by universities, though often without much definition. The research methodology involved thematic analysis of data from in-depth interviews with academics (voluntary participants) in different disciplines and institutions in the UK, Czech Republic and other EU countries. The interviews explored lecturers’ conceptions of ESJ, their practice of it, and associated challenges and enabling factors. Main findings are that ESJ is construed as provision of equitable and conscientising education opportunities that run across the whole higher education (HE) journey, from widening access to HE to stimulating critical learning and awareness that can empower graduates to transform their lives and societies. Teaching practice featured study of topics related to social justice; collaborative and creative learning activities, and assignments offering choice and connection to students’ realities. Student responses could be mixed, occasionally resistant, but mostly positive in terms of gaining increased confidence and awareness of equality and social responsibility. Influences at the macro, meso and mico level could support or limit scope for ESJ. Overall, the study highlights the strong, values-based commitment of HE teachers to facilitating student learning engagement, wellbeing and development towards building a better world.

Keywords: higher education, social justice, inclusivity, diversity

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19 Self-Management among the Ethnic Groups with Type 2 Diabetes Mellitus in Thailand

Authors: Siwarak Kitchanapaibul, Warren Gillibrand, Rob Burton

Abstract:

The prevalence of diabetes mellitus has been rising all over the world. Self-management is required for diabetes mellitus patients. The objective of this study is to explore the self-management among the ethnic groups with type 2 diabetes mellitus in Thailand, an upper middle-income country which is located in South East Asia. The ethnic groups in Thailand are a minority group which has limited education and a different culture, language, costume and lifestyle from Thai people. The qualitative exploratory study was used in this study. In-depth interviews with semi-structured open questions were conducted by 20 participants from purposive sampling. These participants were the ethnic groups who have type 2 diabetes mellitus, received the services from a region hospital, understood Thai and were willing to participate. Content analysis was adopted for the study. The results showed that all of the participants controlled their diet before the appointment day and never miss their appointment. Only 3 participants did their exercise while 2 participants stated that they occasionally forgot to take medicine. 10 participants use the herbs for reducing the sugar level. 12 participants drank a lot of water after a lapse in the diet because they believed that water could dilute the sugar. The findings identified 5 themes; ‘controlling diet before appointment day’; ‘drinking water after a lapse in diet’; ‘medication being a vital importance’; ‘exercise is unimportant’; and ‘taking herbs for sugar reduction’. The results of this study are important to the health professionals to understand the self-management of Ethnic groups and use the data to create the appropriate intervention for promoting health among the ethnic groups with type 2 diabetes mellitus in Thailand. The findings will lead to the revision of health policy and the procedure for promoting health in this special ethnic groups.

Keywords: self-management, diabetes, ethnic groups, Thailand

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18 Comparison of Regional and Local Indwelling Catheter Techniques to Prolong Analgesia in Total Knee Arthroplasty Procedures: Continuous Peripheral Nerve Block and Continuous Periarticular Infiltration

Authors: Jared Cheves, Amanda DeChent, Joyce Pan

Abstract:

Total knee replacements (TKAs) are one of the most common but painful surgical procedures performed in the United States. Currently, the gold standard for postoperative pain management is the utilization of opioids. However, in the wake of the opioid epidemic, the healthcare system is attempting to reduce opioid consumption by trialing innovative opioid sparing analgesic techniques such as continuous peripheral nerve blocks (CPNB) and continuous periarticular infiltration (CPAI). The alleviation of pain, particularly during the first 72 hours postoperatively, is of utmost importance due to its association with delayed recovery, impaired rehabilitation, immunosuppression, the development of chronic pain, the development of rebound pain, and decreased patient satisfaction. While both CPNB and CPAI are being used today, there is limited evidence comparing the two to the current standard of care or to each other. An extensive literature review was performed to explore the safety profiles and effectiveness of CPNB and CPAI in reducing reported pain scores and decreasing opioid consumption. The literature revealed the usage of CPNB contributed to lower pain scores and decreased opioid use when compared to opioid-only control groups. Additionally, CPAI did not improve pain scores or decrease opioid consumption when combined with a multimodal analgesic (MMA) regimen. When comparing CPNB and CPAI to each other, neither unanimously lowered pain scores to a greater degree, but the literature indicates that CPNB decreased opioid consumption more than CPAI. More research is needed to further cement the efficacy of CPNB and CPAI as standard components of MMA in TKA procedures. In addition, future research can also focus on novel catheter-free applications to reduce the complications of continuous catheter analgesics.

Keywords: total knee arthroplasty, continuous peripheral nerve blocks, continuous periarticular infiltration, opioid, multimodal analgesia

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17 Human-Wildlife Conflicts in Urban Areas of Zimbabwe

Authors: Davie G. Dave, Prisca H. Mugabe, Tonderai Mutibvu

Abstract:

Globally, HWCs are on the rise. Such is the case with urban areas in Zimbabwe, yet little has been documented about it. This study was done to provide insights into the occurrence of human-wildlife conflicts in urban areas. The study was carried out in Harare, Bindura, Masvingo, Beitbridge, and Chiredzi to determine the cause, nature, extent, and frequency of occurrence of HWC, to determine the key wildlife species involved in conflicts and management practices done to combat wildlife conflicts in these areas. Several sampling techniques encompassing multi-stage sampling, stratified random, purposive, and simple random sampling were employed for placing residential areas into three strata according to population density, selecting residential areas, and selecting actual participants. Data were collected through a semi-structured questionnaire and key informant interviews. The results revealed that property destruction and crop damage were the most prevalent conflicts. Of the 15 animals that were cited, snakes, baboons, and monkeys were associated with the most conflicts. The occurrence of HWCs was mainly attributed to the increase in both animal and human populations. To curtail these HWCs, the local people mainly used non-lethal methods, whilst lethal methods were used by authorities for some of the reported cases. The majority of the conflicts were seasonal and less severe. There were growing concerns by respondents on the issues of wildlife conflicts, especially in those areas that had primates, such as Warren Park in Harare and Limpopo View in Beitbridge. There are HWCs hotspots in urban areas, and to ameliorate this, suggestions are that there is a need for a multi-action approach that includes general awareness campaigns on HWCs and land use planning that involves the creation of green spaces to ease wildlife management.

Keywords: human-wildlife conflicts, mitigation measures, residential areas, types of conflicts, urban areas

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16 Identifying, Reporting and Preventing Medical Errors Among Nurses Working in Critical Care Units At Kenyatta National Hospital, Kenya: Closing the Gap Between Attitude and Practice

Authors: Jared Abuga, Wesley Too

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Medical error is the third leading cause of death in US, with approximately 98,000 deaths occurring every year as a result of medical errors. The world financial burden of medication errors is roughly USD 42 billion. Medication errors may lead to at least one death daily and injure roughly 1.3 million people every year. Medical error reporting is essential in creating a culture of accountability in our healthcare system. Studies have shown that attitudes and practice of healthcare workers in reporting medical errors showed that the major factors in under-reporting of errors included work stress and fear of medico-legal consequences due to the disclosure of error. Further, the majority believed that increase in reporting medical errors would contribute to a better system. Most hospitals depend on nurses to discover medication errors because they are considered to be the sources of these errors, as contributors or mere observers, consequently, the nurse’s perception of medication errors and what needs to be done is a vital feature to reducing incidences of medication errors. We sought to explore knowledge among nurses on medical errors and factors affecting or hindering reporting of medical errors among nurses working at the emergency unit, KNH. Critical care nurses are faced with many barriers to completing incident reports on medication errors. One of these barriers which contribute to underreporting is a lack of education and/or knowledge regarding medication errors and the reporting process. This study, therefore, sought to determine the availability and the use of reporting systems for medical errors in critical care unity. It also sought to establish nurses’ perception regarding medical errors and reporting and document factors facilitating timely identification and reporting of medical errors in critical care settings. Methods: The study used cross-section study design to collect data from 76 critical care nurses from Kenyatta Teaching & Research National Referral Hospital, Kenya. Data analysis and results is ongoing. By October 2022, we will have analysis, results, discussions, and recommendations of the study for purposes of the conference in 2023

Keywords: errors, medical, kenya, nurses, safety

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15 By Removing High-Performance Aerobic Scope Phenotypes, Capture Fisheries May Reduce the Resilience of Fished Populations to Thermal Variability and Compromise Their Persistence into the Anthropocene.

Authors: Lauren A. Bailey, Amber R. Childs, Nicola C. James, Murray I. Duncan, Alexander Winkler, Warren M. Potts

Abstract:

For the persistence of fished populations in the Anthropocene, it is critical to predict how fished populations will respond to the coupled threats of exploitation and climate change for adaptive management. The resilience of fished populations will depend on their capacity for physiological plasticity and acclimatization in response to environmental shifts. However, there is evidence for the selection of physiological traits by capture fisheries. Hence, fish populations may have a limited scope for the rapid expansion of their tolerance ranges or physiological adaptation under fishing pressures. To determine the physiological vulnerability of fished populations in the Anthropocene, the metabolic performance was compared between a fished and spatially protected Chrysoblephus laticeps population in response to thermal variability. Individual aerobic scope phenotypes were quantified using intermittent flow respirometry by comparing changes in energy expenditure of each individual at ecologically relevant temperatures, mimicking variability experienced as a result of upwelling and downwelling events. The proportion of high and low-performance individuals were compared between the fished and spatially protected population. The fished population had limited aerobic scope phenotype diversity and fewer high-performance phenotypes, resulting in a significantly lower aerobic scope curve across low (10 °C) and high (24 °C) thermal treatments. The performance of fished populations may be compromised with predicted future increases in cold upwelling events. This requires the conservation of the physiologically fittest individuals in spatially protected areas, which can recruit into nearby fished areas, as a climate resilience tool.

Keywords: climate change, fish physiology, metabolic shifts, over-fishing, respirometry

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14 Efficient Reuse of Exome Sequencing Data for Copy Number Variation Callings

Authors: Chen Wang, Jared Evans, Yan Asmann

Abstract:

With the quick evolvement of next-generation sequencing techniques, whole-exome or exome-panel data have become a cost-effective way for detection of small exonic mutations, but there has been a growing desire to accurately detect copy number variations (CNVs) as well. In order to address this research and clinical needs, we developed a sequencing coverage pattern-based method not only for copy number detections, data integrity checks, CNV calling, and visualization reports. The developed methodologies include complete automation to increase usability, genome content-coverage bias correction, CNV segmentation, data quality reports, and publication quality images. Automatic identification and removal of poor quality outlier samples were made automatically. Multiple experimental batches were routinely detected and further reduced for a clean subset of samples before analysis. Algorithm improvements were also made to improve somatic CNV detection as well as germline CNV detection in trio family. Additionally, a set of utilities was included to facilitate users for producing CNV plots in focused genes of interest. We demonstrate the somatic CNV enhancements by accurately detecting CNVs in whole exome-wide data from the cancer genome atlas cancer samples and a lymphoma case study with paired tumor and normal samples. We also showed our efficient reuses of existing exome sequencing data, for improved germline CNV calling in a family of the trio from the phase-III study of 1000 Genome to detect CNVs with various modes of inheritance. The performance of the developed method is evaluated by comparing CNV calling results with results from other orthogonal copy number platforms. Through our case studies, reuses of exome sequencing data for calling CNVs have several noticeable functionalities, including a better quality control for exome sequencing data, improved joint analysis with single nucleotide variant calls, and novel genomic discovery of under-utilized existing whole exome and custom exome panel data.

Keywords: bioinformatics, computational genetics, copy number variations, data reuse, exome sequencing, next generation sequencing

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13 Improving Part-Time Instructors’ Academic Outcomes with Gamification

Authors: Jared R. Chapman

Abstract:

This study introduces a type of motivational information system called an educational engagement information system (EEIS). An EEIS draws on principles of behavioral economics, motivation theory, and learning cognition theory to design information systems that help students want to improve their performance. This study compares academic outcomes for course sections taught by part- and full-time instructors both with and without an EEIS. Without an EEIS, students in the part-time instructor's course sections demonstrated significantly higher failure rates (a 143.8% increase) and dropout rates (a 110.4% increase) with significantly fewer students scoring a B- or higher (39.8% decrease) when compared to students in the course sections taught by a full-time instructor. It is concerning that students in the part-time instructor’s course without an EEIS had significantly lower academic outcomes, suggesting less understanding of the course content. This could impact retention and continuation in a major. With an EEIS, when comparing part- and full-time instructors, there was no significant difference in failure and dropout rates or in the number of students scoring a B- or higher in the course. In fact, with an EEIS, the failure and dropout rates were statistically identical for part- and full-time instructor courses. When using an EEIS (compared with not using an EEIS), the part-time instructor showed a 62.1% decrease in failures, a 61.4% decrease in dropouts, and a 41.7% increase in the number of students scoring a B- or higher in the course. We are unaware of other interventions that yield such large improvements in academic performance. This suggests that using an EEIS such as Delphinium may compensate for part-time instructors’ limitations of expertise, time, or rewards that can have a negative impact on students’ academic outcomes. The EEIS had only a minimal impact on failure rates (7.7% decrease) and dropout rates (18.8% decrease) for the full-time instructor. This suggests there is a ceiling effect for the improvements that an EEIS can make in student performance. This may be because experienced instructors are already doing the kinds of things that an EEIS does, such as motivating students, tracking grades, and providing feedback about progress. Additionally, full-time instructors have more time to dedicate to students outside of class than part-time instructors and more rewards for doing so. Using adjunct and other types of part-time instructors will likely remain a prevalent practice in higher education management courses. Given that using part-time instructors can have a negative impact on student graduation and persistence in a field of study, it is important to identify ways we can augment part-time instructors’ performance. We demonstrated that when part-time instructors use an EEIS, it can result in significantly lower students’ failure and dropout rates and an increase in the rate of students earning a B- or above; and bring their students’ performance to parity with the performance of students taught by a full-time instructor.

Keywords: gamification, engagement, motivation, academic outcomes

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12 Assessing the Impact of High Fidelity Human Patient Simulation on Teamwork among Nursing, Medicine and Pharmacy Undergraduate Students

Authors: S. MacDonald, A. Manuel, R. Law, N. Bandruak, A. Dubrowski, V. Curran, J. Smith-Young, K. Simmons, A. Warren

Abstract:

High fidelity human patient simulation has been used for many years by health sciences education programs to foster critical thinking, engage learners, improve confidence, improve communication, and enhance psychomotor skills. Unfortunately, there is a paucity of research on the use of high fidelity human patient simulation to foster teamwork among nursing, medicine and pharmacy undergraduate students. This study compared the impact of high fidelity and low fidelity simulation education on teamwork among nursing, medicine and pharmacy students. For the purpose of this study, two innovative teaching scenarios were developed based on the care of an adult patient experiencing acute anaphylaxis: one high fidelity using a human patient simulator and one low fidelity using case based discussions. A within subjects, pretest-posttest, repeated measures design was used with two-treatment levels and random assignment of individual subjects to teams of two or more professions. A convenience sample of twenty-four (n=24) undergraduate students participated, including: nursing (n=11), medicine (n=9), and pharmacy (n=4). The Interprofessional Teamwork Questionnaire was used to assess for changes in students’ perception of their functionality within the team, importance of interprofessional collaboration, comprehension of roles, and confidence in communication and collaboration. Student satisfaction was also assessed. Students reported significant improvements in their understanding of the importance of interprofessional teamwork and of the roles of nursing and medicine on the team after participation in both the high fidelity and the low fidelity simulation. However, only participants in the high fidelity simulation reported a significant improvement in their ability to function effectively as a member of the team. All students reported that both simulations were a meaningful learning experience and all students would recommend both experiences to other students. These findings suggest there is merit in both high fidelity and low fidelity simulation as a teaching and learning approach to foster teamwork among undergraduate nursing, medicine and pharmacy students. However, participation in high fidelity simulation may provide a more realistic opportunity to practice and function as an effective member of the interprofessional health care team.

Keywords: acute anaphylaxis, high fidelity human patient simulation, low fidelity simulation, interprofessional education

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11 Improving Screening and Treatment of Binge Eating Disorders in Pediatric Weight Management Clinic through a Quality Improvement Framework

Authors: Cristina Fernandez, Felix Amparano, John Tumberger, Stephani Stancil, Sarah Hampl, Brooke Sweeney, Amy R. Beck, Helena H Laroche, Jared Tucker, Eileen Chaves, Sara Gould, Matthew Lindquist, Lora Edwards, Renee Arensberg, Meredith Dreyer, Jazmine Cedeno, Alleen Cummins, Jennifer Lisondra, Katie Cox, Kelsey Dean, Rachel Perera, Nicholas A. Clark

Abstract:

Background: Adolescents with obesity are at higher risk of disordered eating than the general population. Detection of eating disorders (ED) is difficult. Screening questionnaires may aid in early detection of ED. Our team’s prior efforts focused on increasing ED screening rates to ≥90% using a validated 10-question adolescent binge eating disorder screening questionnaire (ADO-BED). This aim was achieved. We then aimed to improve treatment plan initiation of patients ≥12 years of age who screen positive for BED within our WMC from 33% to 70% within 12 months. Methods: Our WMC is within a tertiary-care, free-standing children’s hospital. A3, an improvement framework, was used. A multidisciplinary team (physicians, nurses, registered dietitians, psychologists, and exercise physiologists) was created. The outcome measure was documentation of treatment plan initiation of those who screen positive (goal 70%). The process measure was ADO-BED screening rate of WMC patients (goal ≥90%). Plan-Do-Study-Act (PDSA) cycle 1 included provider education on current literature and treatment plan initiation based upon ADO-BED responses. PDSA 2 involved increasing documentation of treatment plan and retrain process to providers. Pre-defined treatment plans were: 1) repeat screen in 3-6 months, 2) resources provided only, or 3) comprehensive multidisciplinary weight management team evaluation. Run charts monitored impact over time. Results: Within 9 months, 166 patients were seen in WMC. Process measure showed sustained performance above goal (mean 98%). Outcome measure showed special cause improvement from mean of 33% to 100% (n=31). Of treatment plans provided, 45% received Plan 1, 4% Plan 2, and 46% Plan 3. Conclusion: Through a multidisciplinary improvement team approach, we maintained sustained ADO-BED screening performance, and, prior to our 12-month timeline, achieved our project aim. Our efforts may serve as a model for other multidisciplinary WMCs. Next steps may include expanding project scope to other WM programs.

Keywords: obesity, pediatrics, clinic, eating disorder

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10 A Corpus Output Error Analysis of Chinese L2 Learners From America, Myanmar, and Singapore

Authors: Qiao-Yu Warren Cai

Abstract:

Due to the rise of big data, building corpora and using them to analyze ChineseL2 learners’ language output has become a trend. Various empirical research has been conducted using Chinese corpora built by different academic institutes. However, most of the research analyzed the data in the Chinese corpora usingcorpus-based qualitative content analysis with descriptive statistics. Descriptive statistics can be used to make summations about the subjects or samples that research has actually measured to describe the numerical data, but the collected data cannot be generalized to the population. Comte, a Frenchpositivist, has argued since the 19th century that human beings’ knowledge, whether the discipline is humanistic and social science or natural science, should be verified in a scientific way to construct a universal theory to explain the truth and human beings behaviors. Inferential statistics, able to make judgments of the probability of a difference observed between groups being dependable or caused by chance (Free Geography Notes, 2015)and to infer from the subjects or examples what the population might think or behave, is just the right method to support Comte’s argument in the field of TCSOL. Also, inferential statistics is a core of quantitative research, but little research has been conducted by combing corpora with inferential statistics. Little research analyzes the differences in Chinese L2 learners’ language corpus output errors by using theOne-way ANOVA so that the findings of previous research are limited to inferring the population's Chinese errors according to the given samples’ Chinese corpora. To fill this knowledge gap in the professional development of Taiwanese TCSOL, the present study aims to utilize the One-way ANOVA to analyze corpus output errors of Chinese L2 learners from America, Myanmar, and Singapore. The results show that no significant difference exists in ‘shì (是) sentence’ and word order errors, but compared with Americans and Singaporeans, it is significantly easier for Myanmar to have ‘sentence blends.’ Based on the above results, the present study provides an instructional approach and contributes to further exploration of how Chinese L2 learners can have (and use) learning strategies to lower errors.

Keywords: Chinese corpus, error analysis, one-way analysis of variance, Chinese L2 learners, Americans, myanmar, Singaporeans

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9 Safety Validation of Black-Box Autonomous Systems: A Multi-Fidelity Reinforcement Learning Approach

Authors: Jared Beard, Ali Baheri

Abstract:

As autonomous systems become more prominent in society, ensuring their safe application becomes increasingly important. This is clearly demonstrated with autonomous cars traveling through a crowded city or robots traversing a warehouse with heavy equipment. Human environments can be complex, having high dimensional state and action spaces. This gives rise to two problems. One being that analytic solutions may not be possible. The other is that in simulation based approaches, searching the entirety of the problem space could be computationally intractable, ruling out formal methods. To overcome this, approximate solutions may seek to find failures or estimate their likelihood of occurrence. One such approach is adaptive stress testing (AST) which uses reinforcement learning to induce failures in the system. The premise of which is that a learned model can be used to help find new failure scenarios, making better use of simulations. In spite of these failures AST fails to find particularly sparse failures and can be inclined to find similar solutions to those found previously. To help overcome this, multi-fidelity learning can be used to alleviate this overuse of information. That is, information in lower fidelity can simulations can be used to build up samples less expensively, and more effectively cover the solution space to find a broader set of failures. Recent work in multi-fidelity learning has passed information bidirectionally using “knows what it knows” (KWIK) reinforcement learners to minimize the number of samples in high fidelity simulators (thereby reducing computation time and load). The contribution of this work, then, is development of the bidirectional multi-fidelity AST framework. Such an algorithm, uses multi-fidelity KWIK learners in an adversarial context to find failure modes. Thus far, a KWIK learner has been used to train an adversary in a grid world to prevent an agent from reaching its goal; thus demonstrating the utility of KWIK learners in an AST framework. The next step is implementation of the bidirectional multi-fidelity AST framework described. Testing will be conducted in a grid world containing an agent attempting to reach a goal position and adversary tasked with intercepting the agent as demonstrated previously. Fidelities will be modified by adjusting the size of a time-step, with higher-fidelity effectively allowing for more responsive closed loop feedback. Results will compare the single KWIK AST learner with the multi-fidelity algorithm with respect to number of samples, distinct failure modes found, and relative effect of learning after a number of trials.

Keywords: multi-fidelity reinforcement learning, multi-fidelity simulation, safety validation, falsification

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8 Behavioral Analysis of Stock Using Selective Indicators from Fundamental and Technical Analysis

Authors: Vish Putcha, Chandrasekhar Putcha, Siva Hari

Abstract:

In the current digital era of free trading and pandemic-driven remote work culture, markets worldwide gained momentum for retail investors to trade from anywhere easily. The number of retail traders rose to 24% of the market from 15% at the pre-pandemic level. Most of them are young retail traders with high-risk tolerance compared to the previous generation of retail traders. This trend boosted the growth of subscription-based market predictors and market data vendors. Young traders are betting on these predictors, assuming one of them is correct. However, 90% of retail traders are on the losing end. This paper presents multiple indicators and attempts to derive behavioral patterns from the underlying stocks. The two major indicators that traders and investors follow are technical and fundamental. The famous investor, Warren Buffett, adheres to the “Value Investing” method that is based on a stock’s fundamental Analysis. In this paper, we present multiple indicators from various methods to understand the behavior patterns of stocks. For this research, we picked five stocks with a market capitalization of more than $200M, listed on the exchange for more than 20 years, and from different industry sectors. To study the behavioral pattern over time for these five stocks, a total of 8 indicators are chosen from fundamental, technical, and financial indicators, such as Price to Earning (P/E), Price to Book Value (P/B), Debt to Equity (D/E), Beta, Volatility, Relative Strength Index (RSI), Moving Averages and Dividend yields, followed by detailed mathematical Analysis. This is an interdisciplinary paper between various disciplines of Engineering, Accounting, and Finance. The research takes a new approach to identify clear indicators affecting stocks. Statistical Analysis of the data will be performed in terms of the probabilistic distribution, then follow and then determine the probability of the stock price going over a specific target value. The Chi-square test will be used to determine the validity of the assumed distribution. Preliminary results indicate that this approach is working well. When the complete results are presented in the final paper, they will be beneficial to the community.

Keywords: stock pattern, stock market analysis, stock predictions, trading, investing, fundamental analysis, technical analysis, quantitative trading, financial analysis, behavioral analysis

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7 Governance of Social Media Using the Principles of Community Radio

Authors: Ken Zakreski

Abstract:

Regulating Canadian Facebook Groups, of a size and type, when they reach a threshold of audio video content. Consider the evolution of the Streaming Act, Parl GC Bill C-11 (44-1) and the regulations that will certainly follow. The Canadian Heritage Minister's office stipulates, "the Broadcasting Act only applies to audio and audiovisual content, not written journalism.” Governance— After 10 years, a community radio station for Gabriola Island, BC – Canadian Radio-television and Telecommunications Commission (“CRTC”) was approved but never started – became a Facebook Group “Community Bulletin Board - Life on Gabriola“ referred to as CBBlog. After CBBlog started and began to gather real traction, a member of the Group cloned the membership and ran their competing Facebook group under the banner of "free speech”. Here we see an inflection point [change of cultural stewardship] with two different mathematical results [engagement and membership growth]. Canada's telecommunication history of “portability” and “interoperability” made that Facebook Group CBBlog the better option, over broadcast FM radio for a community pandemic information sharing service for Gabriola Island, BC. A culture of ignorance flourishes in social media. Often people do not understand their own experience, or the experience of others because they do not have the concepts needed for understanding. It is thus important they are not denied concepts required for their full understanding. For example, Legislators need to know something about gay culture before they can make any decisions about it. Community Media policies and CRTC regulations are known and regulators can use that history to forge forward with regulations for internet platforms of a size and content type that reach a threshold of audio / video content. Mostly volunteer run media services, provide order of magnitude lower costs over commercial media. (Treating) Facebook Groups as new media.? Cathy Edwards, executive director of the Canadian Association of Community Television Users and Stations (“CACTUS”), calls it new media in that the distribution platform is not the issue. What does make community groups community media? Cathy responded, "... it's bylaws, articles of incorporation that state they are community media, they have accessibility, commitments to skills training, any member of the community can be a member, and there is accountability to a board of directors". Eligibility for funding through CACTUS requires these same commitments. It is risky for a community to invest into a platform as ownership has not been litigated. Is a FaceBook Group an asset of a not for profit society? The memo, from law student, Jared Hubbard summarizes, “Rights and interests in a Facebook group could, in theory, be transferred as property... This theory is currently unconfirmed by Canadian courts. “

Keywords: social media, governance, community media, Canadian radio

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6 ‘Nature Will Slow You Down for a Reason’: Virtual Elder-Led Support Services during COVID-19

Authors: Grandmother Roberta Oshkawbewisens, Elder Isabelle Meawasige, Lynne Groulx, Chloë Hamilton, Lee Allison Clark, Dana Hickey, Wansu Qiu, Jared Leedham, Nishanthini Mahendran, Cameron Maclaine

Abstract:

In March of 2020, the world suddenly shifted with the onset of the COVID-19 pandemic; in-person programs and services were unavailable and a scramble to shift to virtual service delivery began. The Native Women’s Association of Canada (NWAC) established virtual programming through the Resiliency Lodge model and connected with Indigenous women, girls, Two-Spirit, transgender, and gender-diverse people across Turtle Island and Inuit Nunangat through programs that provide a safe space to slow down and reflect on their lives, environment, and well-being. To continue to grow the virtual Resiliency Lodge model, NWAC needed to develop an understanding of three questions: how COVID-19 affects Elder-led support services, how Elder-led support services have adapted during the pandemic, and what Wise Practices need to be implemented to continue to develop, refine, and evaluate virtual Elder-led support services specifically for Indigenous women, girls, two-Spirit, transgender, and gender-diverse people. Through funding from the Canadian Institute of Health Research (CIHR), NWAC gained deeper insight into these questions and developed a series of key findings and recommendations that are outlined throughout this report. The goals of this project are to contribute to a more robust participatory analysis that reflects the complexities of Elder-led virtual cultural responses and the impacts of COVID-19 on Elder-led support services; develop culturally and contextually meaningful virtual protocols and wise practices for virtual Indigenous-led support; and develop an Evaluation Strategy to improve the capacity of the Resiliency Lodge model. Significant findings from the project include Resiliency Lodge programs, especially crafting and business sessions, have provided participants with a sense of community and contributed to healing and wellness; Elder-led support services need greater and more stable funding to offer more workshops to more Indigenous women, girls, Two-Spirit, transgender, and gender-diverse people; and Elder- and Indigenous-led programs play a significant role in healing and building a sense of purpose and belonging among Indigenous people. Ultimately, the findings and recommendations outlined in this research project help to guide future Elder-led virtual support services and emphasize the critical need to increase access to Elder-led programming for Indigenous women, girls, Two-Spirit, transgender, and gender-diverse people.

Keywords: indigenous women, traditional healing, virtual programs, covid-19

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5 Examining the Links between Fish Behaviour and Physiology for Resilience in the Anthropocene

Authors: Lauren A. Bailey, Amber R. Childs, Nicola C. James, Murray I. Duncan, Alexander Winkler, Warren M. Potts

Abstract:

Changes in behaviour and physiology are the most important responses of marine life to anthropogenic impacts such as climate change and over-fishing. Behavioural changes (such as a shift in distribution or changes in phenology) can ensure that a species remains in an environment suited for its optimal physiological performance. However, if marine life is unable to shift their distribution, they are reliant on physiological adaptation (either by broadening their metabolic curves to tolerate a range of stressors or by shifting their metabolic curves to maximize their performance at extreme stressors). However, since there are links between fish physiology and behaviour, changes to either of these traits may have reciprocal interactions. This paper reviews the current knowledge of the links between the behaviour and physiology of fishes, discusses these in the context of exploitation and climate change, and makes recommendations for future research needs. The review revealed that our understanding of the links between fish behaviour and physiology is rudimentary. However, both are hypothesized to be linked to stress responses along the hypothalamic pituitary axis. The link between physiological capacity and behaviour is particularly important as both determine the response of an individual to a changing climate and are under selection by fisheries. While it appears that all types of capture fisheries are likely to reduce the adaptive potential of fished populations to climate stressors, angling, which is primarily associated with recreational fishing, may induce fission of natural populations by removing individuals with bold behavioural traits and potentially the physiological traits required to facilitate behavioural change. Future research should focus on assessing how the links between physiological capacity and behaviour influence catchability, the response to climate change drivers, and post-release recovery. The plasticity of phenotypic traits should be examined under a range of stressors of differing intensity in several species and life history stages. Future studies should also assess plasticity (fission or fusion) in the phenotypic structuring of social hierarchy and how this influences habitat selection. Ultimately, to fully understand how physiology is influenced by the selective processes driven by fisheries, long-term monitoring of the physiological and behavioural structure of fished populations, their fitness, and catch rates are required.

Keywords: climate change, metabolic shifts, over-fishing, phenotypic plasticity, stress response

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4 Investigation of the IL23R Psoriasis/PsA Susceptibility Locus

Authors: Shraddha Rane, Richard Warren, Stephen Eyre

Abstract:

L-23 is a pro-inflammatory molecule that signals T cells to release cytokines such as IL-17A and IL-22. Psoriasis is driven by a dysregulated immune response, within which IL-23 is now thought to play a key role. Genome-wide association studies (GWAS) have identified a number of genetic risk loci that support the involvement of IL-23 signalling in psoriasis; in particular a robust susceptibility locus at a gene encoding a subunit of the IL-23 receptor (IL23R) (Stuart et al., 2015; Tsoi et al., 2012). The lead psoriasis-associated SNP rs9988642 is located approximately 500 bp downstream of IL23R but is in tight linkage disequilibrium (LD) with a missense SNP rs11209026 (R381Q) within IL23R (r2 = 0.85). The minor (G) allele of rs11209026 is present in approximately 7% of the population and is protective for psoriasis and several other autoimmune diseases including IBD, ankylosing spondylitis, RA and asthma. The psoriasis-associated missense SNP R381Q causes an arginine to glutamine substitution in a region of the IL23R protein between the transmembrane domain and the putative JAK2 binding site in the cytoplasmic portion. This substitution is expected to affect the receptor’s surface localisation or signalling ability, rather than IL23R expression. Recent studies have also identified a psoriatic arthritis (PsA)-specific signal at IL23R; thought to be independent from the psoriasis association (Bowes et al., 2015; Budu-Aggrey et al., 2016). The lead PsA-associated SNP rs12044149 is intronic to IL23R and is in LD with likely causal SNPs intersecting promoter and enhancer marks in memory CD8+ T cells (Budu-Aggrey et al., 2016). It is therefore likely that the PsA-specific SNPs affect IL23R function via a different mechanism compared with the psoriasis-specific SNPs. It could be hypothesised that the risk allele for PsA located within the IL23R promoter causes an increase IL23R expression, relative to the protective allele. An increased expression of IL23R might then lead to an exaggerated immune response. The independent genetic signals identified for psoriasis and PsA in this locus indicate that different mechanisms underlie these two conditions; although likely both affecting the function of IL23R. It is very important to further characterise these mechanisms in order to better understand how the IL-23 receptor and its downstream signalling is affected in both diseases. This will help to determine how psoriasis and PsA patients might differentially respond to therapies, particularly IL-23 biologics. To investigate this further we have developed an in vitro model using CD4 T cells which express either wild type IL23R and IL12Rβ1 or mutant IL23R (R381Q) and IL12Rβ1. Model expressing different isotypes of IL23R is also underway to investigate the effects on IL23R expression. We propose to further investigate the variants for Ps and PsA and characterise key intracellular processes related to the variants.

Keywords: IL23R, psoriasis, psoriatic arthritis, SNP

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3 Kitchen Bureaucracy: The Preparation of Banquets for Medieval Japanese Royalty

Authors: Emily Warren

Abstract:

Despite the growing body of research on Japanese food history, little has been written about the attitudes and perspectives premodern Japanese people held about their food, even on special celebratory days. In fact, the overall image that arises from the literature is one of ambivalence: that the medieval nobility of the Heian and Kamakura periods (795-1333) did not much care about what they ate and for that reason, food seems relatively scarce in certain historical records. This study challenges this perspective by analyzing the manuals written to guide palace management and feast preparation for royals, introducing two of the sources into English for the first time. This research is primarily based on three manuals that address different aspects of royal food culture and preparation. The Chujiruiki, or Record of the Palace Kitchens (1295), is a fragmentary manual written by a bureaucrat in charge of the main palace kitchen office. This document collection details the utensils, furnishing, and courses that officials organized for the royals’ two daily meals in the morning (asagarei gozen) and in the afternoon (hiru gozen) when they enjoyed seven courses, each one carefully cooked and plated. The orchestration of daily meals and frequent banquets would have been complicated affairs for those preparing the tableware and food, thus requiring texts like the Chûjiruiki, as well as another manual, the Nicchûgyôji (11th c.), or The Daily Functions. Because of the complex coordination between various kitchen-related bureaucratic offices, kitchen officials endeavored to standardize the menus and place settings depending on the time of year, religious abstinence days, and available ingredients flowing into the capital as taxes. For the most important annual banquets and rites celebrating deities and the royal family, kitchen officials would likely refer to the Engi Shiki (927), or Protocols of the Engi Era, for details on offerings, servant payments, and menus. This study proposes that many of the great feast events, and indeed even daily meals at the palace, were so standardized and carefully planned for repetition that there would have been little need for the contents of such feasts to be detailed in diaries or novels—places where historians have noted a lack of the mention of food descriptions. These descriptions were not included for lack of interest on the part of the nobility, but rather because knowledge of what would be served at banquets and feasts would be considered a matter-of-course in the same way that a modern American would likely not need to state the menu of a traditional Thanksgiving meal to an American audience. Where food was concerned, novelty more so than tradition prompted a response in personal records, like diaries.

Keywords: banquets, bureaucracy, Engi shiki, Japanese food

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2 Switchable Lipids: From a Molecular Switch to a pH-Sensitive System for the Drug and Gene Delivery

Authors: Jeanne Leblond, Warren Viricel, Amira Mbarek

Abstract:

Although several products have reached the market, gene therapeutics are still in their first stages and require optimization. It is possible to improve their lacking efficiency by the use of carefully engineered vectors, able to carry the genetic material through each of the biological barriers they need to cross. In particular, getting inside the cell is a major challenge, because these hydrophilic nucleic acids have to cross the lipid-rich plasmatic and/or endosomal membrane, before being degraded into lysosomes. It takes less than one hour for newly endocytosed liposomes to reach highly acidic lysosomes, meaning that the degradation of the carried gene occurs rapidly, thus limiting the transfection efficiency. We propose to use a new pH-sensitive lipid able to change its conformation upon protonation at endosomal pH values, leading to the disruption of the lipidic bilayer and thus to the fast release of the nucleic acids into the cytosol. It is expected that this new pH-sensitive mechanism promote endosomal escape of the gene, thereby its transfection efficiency. The main challenge of this work was to design a preparation presenting fast-responding lipidic bilayer destabilization properties at endosomal pH 5 while remaining stable at blood pH value and during storage. A series of pH-sensitive lipids able to perform a conformational switch upon acidification were designed and synthesized. Liposomes containing these switchable lipids, as well as co-lipids were prepared and characterized. The liposomes were stable at 4°C and pH 7.4 for several months. Incubation with siRNA led to the full entrapment of nucleic acids as soon as the positive/negative charge ratio was superior to 2. The best liposomal formulation demonstrated a silencing efficiency up to 10% on HeLa cells, very similar to a commercial agent, with a lowest toxicity than the commercial agent. Using flow cytometry and microscopy assays, we demonstrated that drop of pH was required for the transfection efficiency, since bafilomycin blocked the transfection efficiency. Additional evidence was brought by the synthesis of a negative control lipid, which was unable to switch its conformation, and consequently exhibited no transfection ability. Mechanistic studies revealed that the uptake was mediated through endocytosis, by clathrin and caveolae pathways, as reported for previous lipid nanoparticle systems. This potent system was used for the treatment of hypercholesterolemia. The switchable lipids were able to knockdown PCSK9 expression on human hepatocytes (Huh-7). Its efficiency is currently evaluated on in vivo mice model of PCSK9 KO mice. In summary, we designed and optimized a new cationic pH-sensitive lipid for gene delivery. Its transfection efficiency is similar to the best available commercial agent, without the usually associated toxicity. The promising results lead to its use for the treatment of hypercholesterolemia on a mice model. Anticancer applications and pulmonary chronic disease are also currently investigated.

Keywords: liposomes, siRNA, pH-sensitive, molecular switch

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