Search results for: cognitive behavioral therapy (CBT)
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4281

Search results for: cognitive behavioral therapy (CBT)

291 Towards a More Inclusive Society: A Study on the Assimilation and Integration of the Migrant Children in Kerala

Authors: Arun Perumbilavil Anand

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For the past few years, the state of Kerala has been witnessing a large inflow of migrant workers from other states of the country, which emerged as a result of demographic transition and Gulf emigration. The in-migration patterns in Kerala have changed over the time with the migrants having a higher residence history bringing their families to the state, thereby making the process more complicated and divergent in its approach. These developments have led to an increase in the young migrant population at least in some parts of the state, which has opened up doubts and questions related to their future in the host society. At this juncture, the study ponders into the factors that are associated with the assimilation and wellbeing of migrant children in the society of Kerala. As one of the objectives, the study also analyzed the influence and role played by the educational institutions (both public and private) in meeting the needs and aspirations of both the children and their parents. The study gains significance as it tries to identify various impediments that hinder the cognitive skill formation and behaviour patterns of the migrant children in the host society. Data and Methodology: The study is based on the primary data collected through a series of interviews and interactions held with parents, children, and teachers of different educational institutions, including both public and private. The primary survey also made use of research techniques like observation, in-depth interviews, and case study method. The study was conducted in schools in the Kanjikode area of the Palakkad district in Kerala. The findings of the study are on the basis of a survey conducted in four schools and 40 migrant children. Findings: The study found that majority of the children have wholly integrated and assimilated into the host society. The influence of the peer group was quite visible in giving stimulus to the assimilation process. Most of the children do not have any emotional or cultural sentiments attached to their state of origin, and they consider Kerala as their ‘home state’ and the local language (Malayalam) as their ‘mother tongue'. The study could also find that the existing education system in the host society fails to meet the needs and aspirations of migrants as well as that of their children. On a comparative scale, to some extent, private schools have succeeded in fulfiling the special requirements of the migrant children. An interesting point that the study could pinpoint at is that the children of the migrants show better health conditions and wellbeing than compared to the natives, which is usually addressed as an epidemiologic paradox. As a concluding remark, the study recommends the inclusion concept of inclusive education into the education system of the state with giving due emphasis on those who are at higher risk of being excluded or marginalized, along with fostering increased interaction between diverse groups.

Keywords: assimilation, Kerala, migrant children, well-being

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290 Plastic Waste Sorting by the People of Dakar

Authors: E. Gaury, P. Mandausch, O. Picot, A. R. Thomas, L. Veisblat, L. Ralambozanany, C. Delsart

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In Dakar, demographic and spatial growth was accompanied by a 50% increase in household waste between 1988 and 2008 in the city. In addition, a change in the nature of household waste was observed between 1990 and 2007. The share of plastic increased by 15% between 2004 and 2007 in Dakar. Plastics represent the seventh category of household waste, the most produced per year in Senegal. The share of plastic in household and similar waste is 9% in Senegal. Waste management in the city of Dakar is a complex process involving a multitude of formal and informal actors with different perceptions and objectives. The objective of this study was to understand the motivations that could lead to sorting action, as well as the perception of plastic waste sorting within the Dakar population (households and institutions). The problematic of this study was as follows: what may be the factors playing a role in the sorting action? In an attempt to answer this, two approaches have been developed: (1) An exploratory qualitative study by semi-structured interviews with two groups of individuals concerned by the sorting of plastic waste: on the one hand, the experts in charge of waste management and on the other the households-producers of waste plastics. This study served as the basis for formulating the hypotheses and thus for the quantitative analysis. (2) A quantitative study using a questionnaire survey method among households producing plastic waste in order to test the previously formulated hypotheses. The objective was to have quantitative results representative of the population of Dakar in relation to the behavior and the process inherent in the adoption of the plastic waste sorting action. The exploratory study shows that the perception of state responsibility varies between institutions and households. Public institutions perceive this as a shared responsibility because the problem of plastic waste affects many sectors (health, environmental education, etc.). Their involvement is geared more towards raising awareness and educating young people. As state action is limited, the emergence of private companies in this sector seems logical as they are setting up collection networks to develop a recycling activity. The state plays a moral support role in these activities and encourages companies to do more. The study of the understanding of the action of sorting plastic waste by the population of Dakar through a quantitative analysis was able to demonstrate the attitudes and constraints inherent in the adoption of plastic waste sorting.Cognitive attitude, knowledge, and visible consequences have been shown to correlate positively with sorting behavior. Thus, it would seem that the population of Dakar is more sensitive to what they see and what they know to adopt sorting behavior.It has also been shown that the strongest constraints that could slow down sorting behavior were the complexity of the process, too much time and the lack of infrastructure in which to deposit plastic waste.

Keywords: behavior, Dakar, plastic waste, waste management

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289 Reading and Writing of Biscriptal Children with and Without Reading Difficulties in Two Alphabetic Scripts

Authors: Baran Johansson

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This PhD dissertation aimed to explore children’s writing and reading in L1 (Persian) and L2 (Swedish). It adds new perspectives to reading and writing studies of bilingual biscriptal children with and without reading and writing difficulties (RWD). The study used standardised tests to examine linguistic and cognitive skills related to word reading and writing fluency in both languages. Furthermore, all participants produced two texts (one descriptive and one narrative) in each language. The writing processes and the writing product of these children were explored using logging methodologies (Eye and Pen) for both languages. Furthermore, this study investigated how two bilingual children with RWD presented themselves through writing across their languages. To my knowledge, studies utilizing standardised tests and logging tools to investigate bilingual children’s word reading and writing fluency across two different alphabetic scripts are scarce. There have been few studies analysing how bilingual children construct meaning in their writing, and none have focused on children who write in two different alphabetic scripts or those with RWD. Therefore, some aspects of the systemic functional linguistics (SFL) perspective were employed to examine how two participants with RWD created meaning in their written texts in each language. The results revealed that children with and without RWD had higher writing fluency in all measures (e.g. text lengths, writing speed) in their L2 compared to their L1. Word reading abilities in both languages were found to influence their writing fluency. The findings also showed that bilingual children without reading difficulties performed 1 standard deviation below the mean when reading words in Persian. However, their reading performance in Swedish aligned with the expected age norms, suggesting greater efficient in reading Swedish than in Persian. Furthermore, the results showed that the level of orthographic depth, consistency between graphemes and phonemes, and orthographic features can probably explain these differences across languages. The analysis of meaning-making indicated that the participants with RWD exhibited varying levels of difficulty, which influenced their knowledge and usage of writing across languages. For example, the participant with poor word recognition (PWR) presented himself similarly across genres, irrespective of the language in which he wrote. He employed the listing technique similarly across his L1 and L2. However, the participant with mixed reading difficulties (MRD) had difficulties with both transcription and text production. He produced spelling errors and frequently paused in both languages. He also struggled with word retrieval and producing coherent texts, consistent with studies of monolingual children with poor comprehension or with developmental language disorder. The results suggest that the mother tongue instruction provided to the participants has not been sufficient for them to become balanced biscriptal readers and writers in both languages. Therefore, increasing the number of hours dedicated to mother tongue instruction and motivating the children to participate in these classes could be potential strategies to address this issue.

Keywords: reading, writing, reading and writing difficulties, bilingual children, biscriptal

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288 Problem Based Learning and Teaching by Example in Dimensioning of Mechanisms: Feedback

Authors: Nicolas Peyret, Sylvain Courtois, Gaël Chevallier

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This article outlines the development of the Project Based Learning (PBL) at the level of a last year’s Bachelor’s Degree. This form of pedagogy has for objective to allow a better involving of the students from the beginning of the module. The theoretical contributions are introduced during the project to solving a technological problem. The module in question is the module of mechanical dimensioning method of Supméca a French engineering school. This school issues a Master’s Degree. While the teaching methods used in primary and secondary education are frequently renewed in France at the instigation of teachers and inspectors, higher education remains relatively traditional in its practices. Recently, some colleagues have felt the need to put the application back at the heart of their theoretical teaching. This need is induced by the difficulty of covering all the knowledge deductively before its application. It is therefore tempting to make the students 'learn by doing', even if it doesn’t cover some parts of the theoretical knowledge. The other argument that supports this type of learning is the lack of motivation the students have for the magisterial courses. The role-play allowed scenarios favoring interaction between students and teachers… However, this pedagogical form known as 'pedagogy by project' is difficult to apply in the first years of university studies because of the low level of autonomy and individual responsibility that the students have. The question of what the student actually learns from the initial program as well as the evaluation of the competences acquired by the students in this type of pedagogy also remains an open problem. Thus we propose to add to the pedagogy by project format a regressive part of interventionism by the teacher based on pedagogy by example. This pedagogical scenario is based on the cognitive load theory and Bruner's constructivist theory. It has been built by relying on the six points of the encouragement process defined by Bruner, with a concrete objective, to allow the students to go beyond the basic skills of dimensioning and allow them to acquire the more global skills of engineering. The implementation of project-based teaching coupled with pedagogy by example makes it possible to compensate for the lack of experience and autonomy of first-year students, while at the same time involving them strongly in the first few minutes of the module. In this project, students have been confronted with the real dimensioning problems and are able to understand the links and influences between parameter variations and dimensioning, an objective that we did not reach in classical teaching. It is this form of pedagogy which allows to accelerate the mastery of basic skills and so spend more time on the engineer skills namely the convergence of each dimensioning in order to obtain a validated mechanism. A self-evaluation of the project skills acquired by the students will also be presented.

Keywords: Bruner's constructivist theory, mechanisms dimensioning, pedagogy by example, problem based learning

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287 From Stigma to Solutions: Harnessing Innovation and Local Wisdom to Tackle Harms Associated with Menstrual Seclusion (Chhaupadi) in Nepal

Authors: Sara E. Baumann, Megan A. Rabin, Mary Hawk, Bhimsen Devkota, Kajol Upadhyaya, Guna Raj Shrestha, Brigit Joseph, Annika Agarwal, Jessica G. Burke

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In Nepal, prevailing sociocultural norms associated with menstruation prompt adherence to stringent rules that limit participation in daily activities. Chhaupadi is a specific menstrual tradition in Nepal in which women and girls segregate themselves and follow a series of restrictions during menstruation. Despite having numerous physical and mental health implications, extant interventions have yet to sustainably address the harms associated with chhaupadi. In this study, the authors describe insights garnered from a collaboration with community members in Dailekh district, who formulated their own approaches to mitigate the adverse facets of chhaupadi. Envisaged as an entry point to improve women’s menstrual health experiences, this investigation employed an approach that uses Human-centered Design and a community-engaged approach. The authors conducted a four-day design workshop which unfolded in two phases: The Discovery Phase, to uncover chhaupadi context and key stakeholders, and the Design Phase, to design contextually relevant interventions. Diverse community-members, including those with lived experience practicing chhaupadi, developed five intervention concepts: 1) harnessing Female Community Health Volunteers as role models, for counseling, and raising awareness; 2) focusing on mothers and mother’s groups to instigate behavioral shifts; 3) engaging the broader community in behavior change efforts; 4) empowering fathers to effect change in their homes through counseling and education; and 5) training and emboldening youth to advocate for positive change through advocacy in their schools and homes. This research underscores the importance of employing multi-level approaches tailored to specific stakeholder groups, given Nepal’s rich cultural diversity. The engagement of Female Community Health Volunteers emerged as a promising yet underexplored intervention concept for chhaupadi, warranting broader implementation. Crucially, it is also imperative for interventions to prioritize tackling deleterious aspects of the chhaupadi tradition, emphasizing safety considerations, all while acknowledging chhaupadi’s entrenched cultural history; for some, there are positive aspects of the tradition that women and girls wish to preserve.

Keywords: human-centered design, menstrual health, Nepal, community-engagement, intervention development, women's health, rural health

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286 Rehabilitation Team after Brain Damages as Complex System Integrating Consciousness

Authors: Olga Maksakova

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A work with unconscious patients after acute brain damages besides special knowledge and practical skills of all the participants requires a very specific organization. A lot of said about team approach in neurorehabilitation, usually as for outpatient mode. Rehabilitologists deal with fixed patient problems or deficits (motion, speech, cognitive or emotional disorder). Team-building means superficial paradigm of management psychology. Linear mode of teamwork fits casual relationships there. Cases with deep altered states of consciousness (vegetative states, coma, and confusion) require non-linear mode of teamwork: recovery of consciousness might not be the goal due to phenomenon uncertainty. Rehabilitation team as Semi-open Complex System includes the patient as a part. Patient's response pattern becomes formed not only with brain deficits but questions-stimuli, context, and inquiring person. Teamwork is sourcing of phenomenology knowledge of patient's processes as Third-person approach is replaced with Second- and after First-person approaches. Here is a chance for real-time change. Patient’s contacts with his own body and outward things create a basement for restoration of consciousness. The most important condition is systematic feedbacks to any minimal movement or vegetative signal of the patient. Up to now, recovery work with the most severe contingent is carried out in the mode of passive physical interventions, while an effective rehabilitation team should include specially trained psychologists and psychotherapists. It is they who are able to create a network of feedbacks with the patient and inter-professional ones building up the team. Characteristics of ‘Team-Patient’ system (TPS) are energy, entropy, and complexity. Impairment of consciousness as the absence of linear contact appears together with a loss of essential functions (low energy), vegetative-visceral fits (excessive energy and low order), motor agitation (excessive energy and excessive order), etc. Techniques of teamwork are different in these cases for resulting optimization of the system condition. Directed regulation of the system complexity is one of the recovery tools. Different signs of awareness appear as a result of system self-organization. Joint meetings are an important part of teamwork. Regular or event-related discussions form the language of inter-professional communication, as well as the patient's shared mental model. Analysis of complex communication process in TPS may be useful for creation of the general theory of consciousness.

Keywords: rehabilitation team, urgent rehabilitation, severe brain damage, consciousness disorders, complex system theory

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285 Identification of the Target Genes to Increase the Immunotherapy Response in Bladder Cancer Patients using Computational and Experimental Approach

Authors: Sahar Nasr, Lin Li, Edwin Wang

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Bladder cancer (BLCA) is known as the 13th cause of death among cancer patients worldwide, and ~575,000 new BLCA cases are diagnosed each year. Urothelial carcinoma (UC) is the most prevalent subtype among BLCA patients, which can be categorized into muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Currently, various therapeutic options are available for UC patients, including (1) transurethral resection followed by intravesical instillation of chemotherapeutics or Bacillus Calmette-Guérin for NMIBC patients, (2) neoadjuvant platinum-based chemotherapy (NAC) plus radical cystectomy is the standard of care for localized MIBC patients, and (3) systematic chemotherapy for metastatic UC. However, conventional treatments may lead to several challenges for treating patients. As an illustration, some patients may suffer from recurrence of the disease after the first line of treatment. Recently, immune checkpoint therapy (ICT) has been introduced as an alternative treatment strategy for the first or second line of treatment in advanced or metastatic BLCA patients. Although ICT showed lucrative results for a fraction of BLCA patients, ~80% of patients were not responsive to it. Therefore, novel treatment methods are required to augment the ICI response rate within BLCA patients. It has been shown that the infiltration of T-cells into the tumor microenvironment (TME) is positively correlated with the response to ICT within cancerous patients. Therefore, the goal of this study is to enhance the infiltration of cytotoxic T-cells into TME through the identification of target genes within the tumor that are responsible for the non-T-cell inflamed TME and their inhibition. BLCA bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) and immune score for TCGA samples were used to determine the Pearson correlation score between the expression of different genes and immune score for each sample. The genes with strong negative correlations were selected (r < -0.2). Thereafter, the correlation between the expression of each gene and survival in BLCA patients was calculated using the TCGA data and Cox regression method. The genes that are common in both selected gene lists were chosen for further analysis. Afterward, BLCA bulk and single-cell RNA-sequencing data were ranked based on the expression of each selected gene and the top and bottom 25% samples were used for pathway enrichment analysis. If the pathways related to the T-cell infiltration (e.g., antigen presentation, interferon, or chemokine pathways) were enriched within the low-expression group, the gene was included for downstream analysis. Finally, the selected genes will be used to calculate the correlation between their expression and the infiltration rate of the activated CD+8 T-cells, natural killer cells and the activated dendric cells. A list of potential target genes has been identified and ranked based on the above-mentioned analysis and criteria. SUN-1 got the highest score within the gene list and other identified genes in the literature as benchmarks. In conclusion, inhibition of SUN1 may increase the tumor-infiltrating lymphocytes and the efficacy of ICI in BLCA patients. BLCA tumor cells with and without SUN-1 CRISPR/Cas9 knockout will be injected into the syngeneic mouse model to validate the predicted SUN-1 effect on increasing tumor-infiltrating lymphocytes.

Keywords: data analysis, gene expression analysis, gene identification, immunoinformatic, functional genomics, transcriptomics

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284 CD97 and Its Role in Glioblastoma Stem Cell Self-Renewal

Authors: Niklas Ravn-Boess, Nainita Bhowmick, Takamitsu Hattori, Shohei Koide, Christopher Park, Dimitris Placantonakis

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Background: Glioblastoma (GBM) is the most common and deadly primary brain malignancy in adults. Tumor propagation, brain invasion, and resistance to therapy critically depend on GBM stem-like cells (GSCs); however, the mechanisms that regulate GSC self-renewal are incompletely understood. Given the aggressiveness and poor prognosis of GBM, it is imperative to find biomarkers that could also translate into novel drug targets. Along these lines, we have identified a cell surface antigen, CD97 (ADGRE5), an adhesion G protein-coupled receptor (GPCR), that is expressed on GBM cells but is absent from non-neoplastic brain tissue. CD97 has been shown to promote invasiveness, angiogenesis, and migration in several human cancers, but its frequency of expression and functional role in regulating GBM growth and survival, and its potential as a therapeutic target has not been investigated. Design: We assessed CD97 mRNA and protein expression in patient derived GBM samples and cell lines using publicly available RNA-sequencing datasets and flow cytometry, respectively. To assess CD97 function, we generated shRNA lentiviral constructs that target a sequence in the CD97 extracellular domain (ECD). A scrambled shRNA (scr) with no predicted targets in the genome was used as a control. We evaluated CD97 shRNA lentivirally transduced GBM cells for Ki67, Annexin V, and DAPI. We also tested CD97 KD cells for their ability to self-renew using clonogenic tumorsphere formation assays. Further, we utilized synthetic Abs (sAbs) generated against the ECD of CD97 to test for potential antitumor effects using patient-derived GBM cell lines. Results: CD97 mRNA expression was expressed at high levels in all GBM samples available in the TCGA cohort. We found high levels of surface CD97 protein expression in 6/6 patient-derived GBM cell cultures, but not human neural stem cells. Flow cytometry confirmed downregulation of CD97 in CD97 shRNA lentivirally transduced cells. CD97 KD induced a significant reduction in cell growth in 3 independent GBM cell lines representing mesenchymal and proneural subtypes, which was accompanied by reduced (~20%) Ki67 staining and increased (~30%) apoptosis. Incubation of GBM cells with sAbs (20 ug/ ml) against the ECD of CD97 for 3 days induced GSC differentiation, as determined by the expression of GFAP and Tubulin. Using three unique GBM patient derived cultures, we found that CD97 KD attenuated the ability of GBM cells to initiate sphere formation by over 300 fold, consistent with an impairment in GSC self-renewal. Conclusion: Loss of CD97 expression in patient-derived GBM cells markedly decreases proliferation, induces cell death, and reduces tumorsphere formation. sAbs against the ECD of CD97 reduce tumorsphere formation, recapitulating the phenotype of CD97 KD, suggesting that sAbs that inhibit CD97 function exhibit anti-tumor activity. Collectively, these findings indicate that CD97 is necessary for the proliferation and survival of human GBM cells and identify CD97 as a promising therapeutically targetable vulnerability in GBM.

Keywords: adhesion GPCR, CD97, GBM stem cell, glioblastoma

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283 Working From Home: On the Relationship Between Place Attachment to Work Place, Extraversion and Segmentation Preference to Burnout

Authors: Diamant Irene, Shklarnik Batya

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In on to its widespread effects on health and economic issues, Covid-19 shook the work and employment world. Among the prominent changes during the pandemic is the work-from-home trend, complete or partial, as part of social distancing. In fact, these changes accelerated an existing tendency of work flexibility already underway before the pandemic. Technology and means of advanced communications led to a re-assessment of “place of work” as a physical space in which work takes place. Today workers can remotely carry out meetings, manage projects, work in groups, and different research studies point to the fact that this type of work has no adverse effect on productivity. However, from the worker’s perspective, despite numerous advantages associated with work from home, such as convenience, flexibility, and autonomy, various drawbacks have been identified such as loneliness, reduction of commitment, home-work boundary erosion, all risk factors relating to the quality of life and burnout. Thus, a real need has arisen in exploring differences in work-from-home experiences and understanding the relationship between psychological characteristics and the prevalence of burnout. This understanding may be of significant value to organizations considering a future hybrid work model combining in-office and remote working. Based on Hobfoll’s Theory of Conservation of Resources, we hypothesized that burnout would mainly be found among workers whose physical remoteness from the workplace threatens or hinders their ability to retain significant individual resources. In the present study, we compared fully remote and partially remote workers (hybrid work), and we examined psychological characteristics and their connection to the formation of burnout. Based on the conceptualization of Place Attachment as the cognitive-emotional bond of an individual to a meaningful place and the need to maintain closeness to it, we assumed that individuals characterized with Place Attachment to the workplace would suffer more from burnout when working from home. We also assumed that extrovert individuals, characterized by the need of social interaction at the workplace and individuals with segmentationpreference – a need for separation between different life domains, would suffer more from burnout, especially among fully remote workers relative to partially remote workers. 194 workers, of which 111 worked from home in full and 83 worked partially from home, aged 19-53, from different sectors, were tested using an online questionnaire through social media. The results of the study supported our assumptions. The repercussions of these findings are discussed, relating to future occupational experience, with an emphasis on suitable occupational adjustment according to the psychological characteristics and needs of workers.

Keywords: working from home, burnout, place attachment, extraversion, segmentation preference, Covid-19

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282 The Effect of Paper Based Concept Mapping on Students' Academic Achievement and Attitude in Science Education

Authors: Orhan Akınoğlu, Arif Çömek, Ersin Elmacı, Tuğba Gündoğdu

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The concept map is known to be a powerful tool to organize the ideas and concepts of an individuals’ mind. This tool is a kind of visual map that illustrates the relationships between the concepts of a certain subject. The effect of concept mapping on cognitive and affective qualities is one of the research topics among educational researchers for last decades. We educators want to utilize it both as an instructional tool or an assessment tool in classes. For that reason, this study aimed to determine the effect of concept mapping as a learning strategy in science classes on students’ academic achievement and attitude. The research employed a randomized pre-test post-test control group design. Data collected from 60 sixth grade students participated in the study from a randomly selected primary school in Turkey. Sixth-grade classes of the school were analyzed according to students’ academic achievement, science attitude, gender, mathematics, science courses grades, and their GPAs before the implementation. Two of the classes found to be equivalent (t=0,983, p>0,05) and one of them was defined as experimental and the other one control group randomly. During a 5-weeks period, the experimental group students (N=30) used the paper-based concept mapping method while the control group students (N=30) were taught with the traditional approach according to the science and technology education curriculum for light and sound subject. Both groups were taught by the same teacher who is experienced using concept mapping in science classes. Before the implementation, the teacher explained the theory of the concept maps and showed how to create paper-based concept mapping individually to the experimental group students for two hours. Then for two following hours she asked them to create some concept maps related to their former science subjects and gave them feedback by reviewing their concept maps to be sure that they can create during the implementation. The data were collected by science achievement test, science attitude scale and personal information form. Science achievement test and science attitude scale were implemented as pre-test and post-test while personal information form was implemented just as once. The reliability coefficient of the achievement test was KR20=0,76 and Cronbach’s Alpha of the attitude scale was 0,89. SPSS statistical software was used to analyze the data. According to the results, there was a statistically significant difference between the experimental and control group for academic achievement but not for attitude. The experimental group had significantly greater gains from academic achievement test than the control group (t=0,02, p<0,05). The findings showed that the paper-and-pencil concept mapping can be used as an effective method for students’ academic achievement in science classes. The results have implications for further researches.

Keywords: concept mapping, science education, constructivism, academic achievement, science attitude

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281 Preparation and Characterization of Anti-Acne Dermal Products Based on Erythromycin β-Cyclodextrin Lactide Complex

Authors: Lacramioara Ochiuz, Manuela Hortolomei, Aurelia Vasile, Iulian Stoleriu, Marcel Popa, Cristian Peptu

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Local antibiotherapy is one of the most effective acne therapies. Erythromycin (ER) is a macrolide antibiotic topically administered for over 30 years in the form of gel, ointment or hydroalcoholic solution for the acne therapy. The use of ER as a base for topical dosage forms raises some technological challenges due to the physicochemical properties of this substance. The main disadvantage of ER is the poor water solubility (2 mg/mL) that limits both formulation using hydrophilic bases and skin permeability. Cyclodextrins (CDs) are biocompatible cyclic oligomers of glucose, with hydrophobic core and hydrophilic exterior. CDs are used to improve the bioavailability of drugs by increasing their solubility and/or their rate of dissolution after including the poorly water soluble substances (such as ER) in the hydrophobic cavity of CDs. Adding CDs leads to the increase of solubility and improved stability of the drug substance, increased permeability of substances of low water solubility, decreased toxicity and even to active dose reduction as a result of increased bioavailability. CDs increase skin tolerability by reducing the irritant effect of certain substances. We have included ER to lactide modified β-cyclodextrin, in order to improve the therapeutic effect of topically administered ER. The aims of the present study were to synthesise and describe a new complex with prolonged release of ER with lactide modified β-cyclodextrin (CD-LA_E), to investigate the CD-LA_E complex by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR), to analyse the effect of semisolid base on the in vitro and ex vivo release characteristics of ER in the CD-LA_E complex by assessing the permeability coefficient and the release kinetics by fitting on mathematical models. SEM showed that, by complexation, ER changes its crystal structure and enters the amorphous phase. FTIR analysis has shown that certain specific bands of some groups in the ER structure move during the incapsulation process. The structure of the CD-LA_E complex has a molar ratio of 2.12 to 1 between lactide modified β-cyclodextrin and ER. The three semisolid bases (2% Carbopol, 13% Lutrol 127 and organogel based on Lutrol and isopropyl myristate) show a good capacity for incorporating the CD-LA_E complex, having a content of active ingredient ranging from 98.3% to 101.5% as compared to the declared value of 2% ER. The results of the in vitro dissolution test showed that the ER solubility was significantly increased by CDs incapsulation. The amount of ER released from the CD-LA_E gels was in the range of 76.23% to 89.01%, whereas gels based on ER released a maximum percentage of 26.01% ER. The ex vivo dissolution test confirms the increased ER solubility achieved by complexation, and supports the assumption that the use of this process might increase ER permeability. The highest permeability coefficient was obtained in ER released from gel based on 2% Carbopol: in vitro 33.33 μg/cm2/h, and ex vivo 26.82 μg/cm2/h, respectively. The release kinetics of complexed ER is performed by Fickian diffusion, according to the results obtained by fitting the data in the Korsmeyer-Peppas model.

Keywords: erythromycin, acne, lactide, cyclodextrin

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280 Implementation of Synthesis and Quality Control Procedures of ¹⁸F-Fluoromisonidazole Radiopharmaceutical

Authors: Natalia C. E. S. Nascimento, Mercia L. Oliveira, Fernando R. A. Lima, Leonardo T. C. do Nascimento, Marina B. Silveira, Brigida G. A. Schirmer, Andrea V. Ferreira, Carlos Malamut, Juliana B. da Silva

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Tissue hypoxia is a common characteristic of solid tumors leading to decreased sensitivity to radiotherapy and chemotherapy. In the clinical context, tumor hypoxia assessment employing the positron emission tomography (PET) tracer ¹⁸F-fluoromisonidazole ([¹⁸F]FMISO) is helpful for physicians for planning and therapy adjusting. The aim of this work was to implement the synthesis of 18F-FMISO in a TRACERlab® MXFDG module and also to establish the quality control procedure. [¹⁸F]FMISO was synthesized at Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN/Brazil) using an automated synthesizer (TRACERlab® MXFDG, GE) adapted for the production of [¹⁸F]FMISO. The FMISO chemical standard was purchased from ABX. 18O- enriched water was acquired from Center of Molecular Research. Reagent kits containing eluent solution, acetonitrile, ethanol, 2.0 M HCl solution, buffer solution, water for injections and [¹⁸F]FMISO precursor (dissolved in 2 ml acetonitrile) were purchased from ABX. The [¹⁸F]FMISO samples were purified by Solid Phase Extraction method. The quality requirements of [¹⁸F]FMISO are established in the European Pharmacopeia. According to that reference, quality control of [¹⁸F]FMISO should include appearance, pH, radionuclidic identity and purity, radiochemical identity and purity, chemical purity, residual solvents, bacterial endotoxins, and sterility. The duration of the synthesis process was 53 min, with radiochemical yield of (37.00 ± 0.01) % and the specific activity was more than 70 GBq/µmol. The syntheses were reproducible and showed satisfactory results. In relation to the quality control analysis, the samples were clear and colorless at pH 6.0. The spectrum emission, measured by using a High-Purity Germanium Detector (HPGe), presented a single peak at 511 keV and the half-life, determined by the decay method in an activimeter, was (111.0 ± 0.5) min, indicating no presence of radioactive contaminants, besides the desirable radionuclide (¹⁸F). The samples showed concentration of tetrabutylammonium (TBA) < 50μg/mL, assessed by visual comparison to TBA standard applied in the same thin layer chromatographic plate. Radiochemical purity was determined by high performance liquid chromatography (HPLC) and the results were 100%. Regarding the residual solvents tested, ethanol and acetonitrile presented concentration lower than 10% and 0.04%, respectively. Healthy female mice were injected via lateral tail vein with [¹⁸F]FMISO, microPET imaging studies (15 min) were performed after 2 h post injection (p.i), and the biodistribution was analyzed in five-time points (30, 60, 90, 120 and 180 min) after injection. Subsequently, organs/tissues were assayed for radioactivity with a gamma counter. All parameters of quality control test were in agreement to quality criteria confirming that [¹⁸F]FMISO was suitable for use in non-clinical and clinical trials, following the legal requirements for the production of new radiopharmaceuticals in Brazil.

Keywords: automatic radiosynthesis, hypoxic tumors, pharmacopeia, positron emitters, quality requirements

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279 Knowledge Management Processes as a Driver of Knowledge-Worker Performance in Public Health Sector of Pakistan

Authors: Shahid Razzaq

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The governments around the globe have started taking into considerations the knowledge management dynamics while formulating, implementing, and evaluating the strategies, with or without the conscious realization, for the different public sector organizations and public policy developments. Health Department of Punjab province in Pakistan is striving to deliver quality healthcare services to the community through an efficient and effective service delivery system. Despite of this struggle some employee performance issues yet exists in the form of challenge to government. To overcome these issues department took several steps including HR strategies, use of technologies and focus of hard issues. Consequently, this study was attempted to highlight the importance of soft issue that is knowledge management in its true essence to tackle their performance issues. Knowledge management in public sector is quite an ignored area in the knowledge management-a growing multidisciplinary research discipline. Knowledge-based view of the firm theory asserts the knowledge is the most deliberate resource that can result in competitive advantage for an organization over the other competing organizations. In the context of our study it means for gaining employee performance, organizations have to increase the heterogeneous knowledge bases. The study uses the cross-sectional and quantitative research design. The data is collected from the knowledge workers of Health Department of Punjab, the biggest province of Pakistan. A total of 341 sample size is achieved. The SmartPLS 3 Version 2.6 is used for analyzing the data. The data examination revealed that knowledge management processes has a strong impact on knowledge worker performance. All hypotheses are accepted according to the results. Therefore, it can be summed up that to increase the employee performance knowledge management activities should be implemented. Health Department within province of Punjab introduces the knowledge management infrastructure and systems to make effective availability of knowledge for the service staff. This knowledge management infrastructure resulted in an increase in the knowledge management process in different remote hospitals, basic health units and care centers which resulted in greater service provisions to public. This study is to have theoretical and practical significances. In terms of theoretical contribution, this study is to establish the relationship between knowledge management and performance for the first time. In case of the practical contribution, this study is to give an insight to public sector organizations and government about role of knowledge management in employ performance. Therefore, public policymakers are strongly advised to implement the activities of knowledge management for enhancing the performance of knowledge workers. The current research validated the substantial role of knowledge management in persuading and creating employee arrogances and behavioral objectives. To the best of authors’ knowledge, this study contribute to the impact of knowledge management on employee performance as its originality.

Keywords: employee performance, knowledge management, public sector, soft issues

Procedia PDF Downloads 113
278 Reliability of Clinical Coding in Accurately Estimating the Actual Prevalence of Adverse Drug Event Admissions

Authors: Nisa Mohan

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Adverse drug event (ADE) related hospital admissions are common among older people. The first step in prevention is accurately estimating the prevalence of ADE admissions. Clinical coding is an efficient method to estimate the prevalence of ADE admissions. The objective of the study is to estimate the rate of under-coding of ADE admissions in older people in New Zealand and to explore how clinical coders decide whether or not to code an admission as an ADE. There has not been any research in New Zealand to explore these areas. This study is done using a mixed-methods approach. Two common and serious ADEs in older people, namely bleeding and hypoglycaemia were selected for the study. In study 1, eight hundred medical records of people aged 65 years and above who are admitted to hospital due to bleeding and hypoglycemia during the years 2015 – 2016 were selected for quantitative retrospective medical records review. This selection was made to estimate the proportion of ADE-related bleeding and hypoglycemia admissions that are not coded as ADEs. These files were reviewed and recorded as to whether the admission was caused by an ADE. The hospital discharge data were reviewed to check whether all the ADE admissions identified in the records review were coded as ADEs, and the proportion of under-coding of ADE admissions was estimated. In study 2, thirteen clinical coders were selected to conduct qualitative semi-structured interviews using a general inductive approach. Participants were selected purposively based on their experience in clinical coding. Interview questions were designed in a way to investigate the reasons for the under-coding of ADE admissions. The records review study showed that 35% (Cl 28% - 44%) of the ADE-related bleeding admissions and 22% of the ADE-related hypoglycemia admissions were not coded as ADEs. Although the quality of clinical coding is high across New Zealand, a substantial proportion of ADE admissions were under-coded. This shows that clinical coding might under-estimate the actual prevalence of ADE related hospital admissions in New Zealand. The interviews with the clinical coders added that lack of time for searching for information to confirm an ADE admission, inadequate communication with clinicians, along with coders’ belief that an ADE is a small thing might be the potential reasons for the under-coding of the ADE admissions. This study urges the coding policymakers, auditors, and trainers to engage with the unconscious cognitive biases and short-cuts of the clinical coders. These results highlight that further work is needed on interventions to improve the clinical coding of ADE admissions, such as providing education to coders about the importance of ADEs, education to clinicians about the importance of clear and confirmed medical records entries, availing pharmacist service to improve the detection and clear documentation of ADE admissions and including a mandatory field in the discharge summary about external causes of diseases.

Keywords: adverse drug events, bleeding, clinical coders, clinical coding, hypoglycemia

Procedia PDF Downloads 107
277 The Enlightenment Project in the Arab World: Saudi Arabia as a Case Study in Modern Islamic Thought

Authors: Khawla Almulla

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It is noticed that many Arab intellectuals have called to the need and the importance of enlightenment and its application in their communities, such as Saudi Arabia. To every Islamic state, the Kingdom of Saudi Arabia represents a strategic cornerstone, since it is considered the cradle of Islam. It is the Land of the Two Holy Mosques: the Holy Mosque in Makkah surrounding the Kaaba, towards which all Muslims around the world turn while performing daily prayers and even travel to if possible in order to perform the Hajj (Pilgrimage). It also has the Prophet'ـ‘s Holy Mosque in Al-Madinah Al-Munawarah, which contains the tomb of Prophet Muhammad (pbuh). Therefore, Saudi Arabia occupies an eminent position among Arab and Islamic countries on a religious level. Saudi Arabia has become the most influential country in the Arab world, since it has one-third of the oil resources outside Central Asia, China and Russia .It is the world’s largest producer and exporter of oil. Discovering oil in Saudi Arabia converted it from an important country for Muslims-only to an important country for the major industrial countries and also the developing countries, as well. For various reasons, the diversity of intellectual currents can play a significant role in each community by way of cultural improvement, the development of civilization and the education of people until they become accustomed to accepting or rejecting opinions or ideas which differ from or oppose their own. In addition, the intellectual pluralism and cultural diversity can play a variety of roles. This helps promote dialogue and understanding between different groups or schools of thought. It can also develop cognitive skills, by exchanging ideas and views between different schools and intellectual currents. However, in Saudi Arabia there is much to oppose this plurality. The situation today shows that having a variety of ideologies and differences of cultures are not considered a reasonable way to develop intellectually as an individual or as a country. Rather the opposite is recommended, such that the ideologies of different groups are enough to bring out intellectual conflict and then to the segregation of society. As a consequence, extremism of thought from the different currents in Saudi Arabia has become apparent. This research is of great importance in its exploration of two significant themes. First, it highlights the Saudi Arabian background, in particular the historical, religious and social contexts, in order to understand the background of each religious or liberal movement and find the core of the intellectual differences between them. In addition, the aim of this research is to show the importance of moderation in Islamic thought in Saudi Arabia by tracing the thoughts and views of Dr Salman Al-Odah, whom he has considered to be the most important moderate thinker in Saudi Arabia.

Keywords: Saudi Arabia, intellectual movements, religious movements, extremism, moderation, Salafism, liberalism, Salman Al-Odah

Procedia PDF Downloads 267
276 Integration of EEG and Motion Tracking Sensors for Objective Measure of Attention-Deficit Hyperactivity Disorder in Pre-Schoolers

Authors: Neha Bhattacharyya, Soumendra Singh, Amrita Banerjee, Ria Ghosh, Oindrila Sinha, Nairit Das, Rajkumar Gayen, Somya Subhra Pal, Sahely Ganguly, Tanmoy Dasgupta, Tanusree Dasgupta, Pulak Mondal, Aniruddha Adhikari, Sharmila Sarkar, Debasish Bhattacharyya, Asim Kumar Mallick, Om Prakash Singh, Samir Kumar Pal

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Background: We aim to develop an integrated device comprised of single-probe EEG and CCD-based motion sensors for a more objective measure of Attention-deficit Hyperactivity Disorder (ADHD). While the integrated device (MAHD) relies on the EEG signal (spectral density of beta wave) for the assessment of attention during a given structured task (painting three segments of a circle using three different colors, namely red, green and blue), the CCD sensor depicts movement pattern of the subjects engaged in a continuous performance task (CPT). A statistical analysis of the attention and movement patterns was performed, and the accuracy of the completed tasks was analysed using indigenously developed software. The device with the embedded software, called MAHD, is intended to improve certainty with criterion E (i.e. whether symptoms are better explained by another condition). Methods: We have used the EEG signal from a single-channel dry sensor placed on the frontal lobe of the head of the subjects (3-5 years old pre-schoolers). During the painting of three segments of a circle using three distinct colors (red, green, and blue), absolute power for delta and beta EEG waves from the subjects are found to be correlated with relaxation and attention/cognitive load conditions. While the relaxation condition of the subject hints at hyperactivity, a more direct CCD-based motion sensor is used to track the physical movement of the subject engaged in a continuous performance task (CPT) i.e., separation of the various colored balls from one table to another. We have used our indigenously developed software for the statistical analysis to derive a scale for the objective assessment of ADHD. We have also compared our scale with clinical ADHD evaluation. Results: In a limited clinical trial with preliminary statistical analysis, we have found a significant correlation between the objective assessment of the ADHD subjects with that of the clinician’s conventional evaluation. Conclusion: MAHD, the integrated device, is supposed to be an auxiliary tool to improve the accuracy of ADHD diagnosis by supporting greater criterion E certainty.

Keywords: ADHD, CPT, EEG signal, motion sensor, psychometric test

Procedia PDF Downloads 65
275 Principal Well-Being at Hong Kong: A Quantitative Investigation

Authors: Junjun Chen, Yingxiu Li

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The occupational well-being of school principals has played a vital role in the pursuit of individual and school wellness and success. However, principals’ well-being worldwide is under increasing threat because of the challenging and complex nature of their work and growing demands for school standardisation and accountability. Pressure is particularly acute in the post-pandemicfuture as principals attempt to deal with the impact of the pandemic on top of more regular demands. This is particularly true in Hong Kong, as school principals are increasingly wedged between unparalleled political, social, and academic responsibilities. Recognizing the semantic breadth of well-being, scholars have not determined a single, mutually agreeable definition but agreed that the concept of well-being has multiple dimensions across various disciplines. The multidimensional approach promises more precise assessments of the relationships between well-being and other concepts than the ‘affect-only’ approach or other single domains for capturing the essence of principal well-being. The multiple-dimension well-being concept is adopted in this project to understand principal well-being in this study. This study aimed to understand the situation of principal well-being and its influential drivers with a sample of 670 principals from Hong Kong and Mainland China. An online survey was sent to the participants after the breakout of COVID-19 by the researchers. All participants were well informed about the purposes and procedure of the project and the confidentiality of the data prior to filling in the questionnaire. Confirmatory factor analysis and structural equation modelling performed with Mplus were employed to deal with the dataset. The data analysis procedure involved the following three steps. First, the descriptive statistics (e.g., mean and standard deviation) were calculated. Second, confirmatory factor analysis (CFA) was used to trim principal well-being measurement performed with maximum likelihood estimation. Third, structural equation modelling (SEM) was employed to test the influential factors of principal well-being. The results of this study indicated that the overall of principal well-being were above the average mean score. The highest ranking in this study given by the principals was to their psychological and social well-being (M = 5.21). This was followed by spiritual (M = 5.14; SD = .77), cognitive (M = 5.14; SD = .77), emotional (M = 4.96; SD = .79), and physical well-being (M = 3.15; SD = .73). Participants ranked their physical well-being the lowest. Moreover, professional autonomy, supervisor and collegial support, school physical conditions, professional networking, and social media have showed a significant impact on principal well-being. The findings of this study will potentially enhance not only principal well-being, but also the functioning of an individual principal and a school without sacrificing principal well-being for quality education in the process. This will eventually move one step forward for a new future - a wellness society advocated by OECD. Importantly, well-being is an inside job that begins with choosing to have wellness, whilst supports to become a wellness principal are also imperative.

Keywords: well-being, school principals, quantitative, influential factors

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274 Active Learning through a Game Format: Implementation of a Nutrition Board Game in Diabetes Training for Healthcare Professionals

Authors: Li Jiuen Ong, Magdalin Cheong, Sri Rahayu, Lek Alexander, Pei Ting Tan

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Background: Previous programme evaluations from the diabetes training programme conducted in Changi General Hospital revealed that healthcare professionals (HCPs) are keen to receive advance diabetes training and education, specifically in medical, nutritional therapy. HCPs also expressed a preference for interactive activities over didactic teaching methods to enhance their learning. Since the War on Diabetes was initiated by MOH in 2016, HCPs are challenged to be actively involved in continuous education to be better equipped to reduce the growing burden of diabetes. Hence, streamlining training to incorporate an element of fun is of utmost importance. Aim: The nutrition programme incorporates game play using an interactive board game that aims to provide a more conducive and less stressful environment for learning. The board game could be adapted for training of community HCPs, health ambassadors or caregivers to cope with the increasing demand of diabetes care in the hospital and community setting. Methodology: Stages for game’s conception (Jaffe, 2001) were adopted in the development of the interactive board game ‘Sweet Score™ ’ Nutrition concepts and topics in diabetes self-management are embedded into the game elements of varying levels of difficulty (‘Easy,’ ‘Medium,’ ‘Hard’) including activities such as a) Drawing/ sculpting (Pictionary-like) b)Facts/ Knowledge (MCQs/ True or False) Word definition) c) Performing/ Charades To study the effects of game play on knowledge acquisition and perceived experiences, participants were randomised into two groups, i.e., lecture group (control) and game group (intervention), to test the difference. Results: Participants in both groups (control group, n= 14; intervention group, n= 13) attempted a pre and post workshop quiz to assess the effectiveness of knowledge acquisition. The scores were analysed using paired T-test. There was an improvement of quiz scores after attending the game play (mean difference: 4.3, SD: 2.0, P<0.001) and the lecture (mean difference: 3.4, SD: 2.1, P<0.001). However, there was no significance difference in the improvement of quiz scores between gameplay and lecture (mean difference: 0.9, 95%CI: -0.8 to 2.5, P=0.280). This suggests that gameplay may be as effective as a lecture in terms of knowledge transfer. All the13 HCPs who participated in the game rated 4 out of 5 on the likert scale for the favourable learning experience and relevance of learning to their job, whereas only 8 out of 14 HCPs in the lecture reported a high rating in both aspects. 16. Conclusion: There is no known board game currently designed for diabetes training for HCPs.Evaluative data from future training can provide insights and direction to improve the game format and cover other aspects of diabetes management such as self-care, exercise, medications and insulin management. Further testing of the board game to ensure learning objectives are met is important and can assist in the development of awell-designed digital game as an alternative training approach during the COVID-19 pandemic. Learning through gameplay increases opportunities for HCPs to bond, interact and learn through games in a relaxed social setting and potentially brings more joy to the workplace.

Keywords: active learning, game, diabetes, nutrition

Procedia PDF Downloads 148
273 Evolutionary Advantages of Loneliness with an Agent-Based Model

Authors: David Gottlieb, Jason Yoder

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The feeling of loneliness is not uncommon in modern society, and yet, there is a fundamental lack of understanding in its origins and purpose in nature. One interpretation of loneliness is that it is a subjective experience that punishes a lack of social behavior, and thus its emergence in human evolution is seemingly tied to the survival of early human tribes. Still, a common counterintuitive response to loneliness is a state of hypervigilance, resulting in social withdrawal, which may appear maladaptive to modern society. So far, no computational model of loneliness’ effect during evolution yet exists; however, agent-based models (ABM) can be used to investigate social behavior, and applying evolution to agents’ behaviors can demonstrate selective advantages for particular behaviors. We propose an ABM where each agent contains four social behaviors, and one goal-seeking behavior, letting evolution select the best behavioral patterns for resource allocation. In our paper, we use an algorithm similar to the boid model to guide the behavior of agents, but expand the set of rules that govern their behavior. While we use cohesion, separation, and alignment for simple social movement, our expanded model adds goal-oriented behavior, which is inspired by particle swarm optimization, such that agents move relative to their personal best position. Since agents are given the ability to form connections by interacting with each other, our final behavior guides agent movement toward its social connections. Finally, we introduce a mechanism to represent a state of loneliness, which engages when an agent's perceived social involvement does not meet its expected social involvement. This enables us to investigate a minimal model of loneliness, and using evolution we attempt to elucidate its value in human survival. Agents are placed in an environment in which they must acquire resources, as their fitness is based on the total resource collected. With these rules in place, we are able to run evolution under various conditions, including resource-rich environments, and when disease is present. Our simulations indicate that there is strong selection pressure for social behavior under circumstances where there is a clear discrepancy between initial resource locations, and against social behavior when disease is present, mirroring hypervigilance. This not only provides an explanation for the emergence of loneliness, but also reflects the diversity of response to loneliness in the real world. In addition, there is evidence of a richness of social behavior when loneliness was present. By introducing just two resource locations, we observed a divergence in social motivation after agents became lonely, where one agent learned to move to the other, who was in a better resource position. The results and ongoing work from this project show that it is possible to glean insight into the evolutionary advantages of even simple mechanisms of loneliness. The model we developed has produced unexpected results and has led to more questions, such as the impact loneliness would have at a larger scale, or the effect of creating a set of rules governing interaction beyond adjacency.

Keywords: agent-based, behavior, evolution, loneliness, social

Procedia PDF Downloads 70
272 A Study on the Acquisition of Chinese Classifiers by Vietnamese Learners

Authors: Quoc Hung Le Pham

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In the field of language study, classifier is an interesting research feature. In the world’s languages, some languages have classifier system, some do not. Mandarin Chinese and Vietnamese languages are a rich classifier system, however, because of the language system, the cognitive, cultural differences, so that the syntactic structure of classifier of them also dissimilar. When using Mandarin Chinese classifiers must collocate with nouns or verbs, in the lexical category it is not like nouns or verbs, belong to the open class. But some scholars believe that Mandarin Chinese measure words are similar to English and other Indo European languages. The word hanging on the structure and word formation (suffix), is a closed class. Compared to other languages, such as Chinese, Vietnamese, Thai and other Asian languages are still belonging to the classifier language’s second type, this type of language is classifier, it is in the majority of quantity must exist, and following deictic, anaphoric or quantity appearing together, not separation between its modified noun, also known as numeral classifier language. Main syntactic structure of Chinese classifiers are as follows: ‘quantity+measure+noun’, ‘pronoun+measure+noun’, ‘pronoun+quantity+measure+noun’, ‘prefix+quantity+measure +noun’, ‘quantity +adjective + measure +noun’, ‘ quantity (above 10 whole number), + duo (多)measure +noun’, ‘ quantity (around 10) + measure + duo (多) +noun’. Main syntactic structure of Vietnamese classifiers are: ‘quantity+measure+noun’, ‘ measure+noun+pronoun’, ‘quantity+measure+noun+pronoun’, ‘measure+noun+prefix+ quantity’, ‘quantity+measure+noun+adjective', ‘duo (多) +quanlity+measure+noun’, ‘quantity+measure+adjective+pronoun (quantity word could not be 1)’, ‘measure+adjective+pronoun’, ‘measure+pronoun’. In daily life, classifiers are commonly used, if Chinese learners failed to standardize this using catergory, because the negative impact might occur on their verbal communication. The richness of the Chinese classifier system contributes to the complexity in the study of the system by foreign learners, especially in the inter language of Vietnamese learners. As above mentioned, Vietnamese language also has a rich system of classifiers, however, the basic structure order of two languages are similar but both still have differences. These similarities and dissimilarities between Chinese and Vietnamese classifier systems contribute significantly to the common errors made by Vietnamese students while they acquire Chinese, which are distinct from the errors made by students from the other language background. This article from a comparative perspective of language, has an orientation towards Chinese and Vietnamese languages commonly used in classifiers semantics and structural form two aspects. This comparative study aims to identity Vietnamese students while learning Chinese classifiers may face some negative transference of mother language, beside that through the analysis of the classifiers questionnaire, find out the causes and patterns of the errors they made. As the preliminary analysis shows, Vietnamese students while learning Chinese classifiers made some errors such as: overuse classifier ‘ge’(个); misuse the other classifiers ‘*yi zhang ri ji’(yi pian ri ji), ‘*yi zuo fang zi’(yi jian fang zi), ‘*si zhang jin pai’(si mei jin pai); homonym words ‘dui, shuang, fu, tao’ (对、双、副、套), ‘ke, li’ (颗、粒).

Keywords: acquisition, classifiers, negative transfer, Vietnamse learners

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271 A Standard-Based Competency Evaluation Scale for Preparing Qualified Adapted Physical Education Teachers

Authors: Jiabei Zhang

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Although adapted physical education (APE) teacher preparation programs are available in the nation, a consistent standards-based competency evaluation scale for preparing of qualified personnel for teaching children with disabilities in APE cannot be identified in the literature. The purpose of this study was to develop a standard-based competency evaluation scale for assessing qualifications for teaching children with disabilities in APE. Standard-based competencies were reviewed and identified based on research evidence documented as effective in teaching children with disabilities in APE. A standard-based competency scale was developed for assessing qualifications for teaching children with disabilities in APE. This scale included 20 standard-based competencies and a 4-point Likert-type scale for each standard-based competency. The first standard-based competency is knowledgeable of the causes of disabilities and their effects. The second competency is the ability to assess physical education skills of children with disabilities. The third competency is able to collaborate with other personnel. The fourth competency is knowledgeable of the measurement and evaluation. The fifth competency is to understand federal and state laws. The sixth competency is knowledgeable of the unique characteristics of all learners. The seventh competency is the ability to write in behavioral terms for objectives. The eighth competency is knowledgeable of developmental characteristics. The ninth competency is knowledgeable of normal and abnormal motor behaviors. The tenth competency is the ability to analyze and adapt the physical education curriculums. The eleventh competency is to understand the history and the philosophy of physical education. The twelfth competency is to understand curriculum theory and development. The thirteenth competency is the ability to utilize instructional designs and plans. The fourteenth competency is the ability to create and implement physical activities. The fifteenth competency is the ability to utilize technology applications. The sixteenth competency is to understand the value of program evaluation. The seventeenth competency is to understand professional standards. The eighteenth competency is knowledgeable of the focused instruction and individualized interventions. The nineteenth competency is able to complete a research project independently. The twentieth competency is to teach children with disabilities in APE independently. The 4-point Likert-type scale ranges from 1 for incompetent to 4 for highly competent. This scale is used for assessing if one completing all course works is eligible for receiving an endorsement for teaching children with disabilities in APE, which is completed based on the grades earned on three courses targeted for each standard-based competency. A mean grade received in three courses primarily addressing a standard-based competency will be marked on a competency level in the above scale. The level 4 is marked for a mean grade of A one receives over three courses, the level 3 for a mean grade of B over three courses, and so on. One should receive a mean score of 3 (competent level) or higher (highly competent) across 19 standard-based competencies after completing all courses specified for receiving an endorsement for teaching children with disabilities in APE. The validity, reliability, and objectivity of this standard-based competency evaluation scale are to be documented.

Keywords: evaluation scale, teacher preparation, adapted physical education teachers, and children with disabilities

Procedia PDF Downloads 89
270 Biocompatibility Tests for Chronic Application of Sieve-Type Neural Electrodes in Rats

Authors: Jeong-Hyun Hong, Wonsuk Choi, Hyungdal Park, Jinseok Kim, Junesun Kim

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Identifying the chronic functions of an implanted neural electrode is an important factor in acquiring neural signals through the electrode or restoring the nerve functions after peripheral nerve injury. The purpose of this study was to investigate the biocompatibility of the chronic implanted neural electrode into the sciatic nerve. To do this, a sieve-type neural electrode was implanted at proximal and distal ends of a transected sciatic nerve as an experimental group (Sieve group, n=6), and the end-to-end epineural repair was operated with the cut sciatic nerve as a control group (reconstruction group, n=6). All surgeries were performed on the sciatic nerve of the right leg in Sprague Dawley rats. Behavioral tests were performed before and 1, 4, 7, 10, 14, and weekly days until 5 months following surgery. Changes in sensory function were assessed by measuring paw withdrawal responses to mechanical and cold stimuli. Motor function was assessed by motion analysis using a Qualisys program, which showed a range of motion (ROM) related to the joints. Neurofilament-heavy chain and fibronectin expression were detected 5 months after surgery. In both groups, the paw withdrawal response to mechanical stimuli was slightly decreased from 3 weeks after surgery and then significantly decreased at 6 weeks after surgery. The paw withdrawal response to cold stimuli was increased from 4 days following surgery in both groups and began to decrease from 6 weeks after surgery. The ROM of the ankle joint was showed a similar pattern in both groups. There was significantly increased from 1 day after surgery and then decreased from 4 days after surgery. Neurofilament-heavy chain expression was observed throughout the entire sciatic nerve tissues in both groups. Especially, the sieve group was showed several neurofilaments that passed through the channels of the sieve-type neural electrode. In the reconstruction group, however, a suture line was seen through neurofilament-heavy chain expression up to 5 months following surgery. In the reconstruction group, fibronectin was detected throughout the sciatic nerve. However, in the sieve group, the fibronectin was observed only in the surrounding nervous tissues of an implanted neural electrode. The present results demonstrated that the implanted sieve-type neural electrode induced a focal inflammatory response. However, the chronic implanted sieve-type neural electrodes did not cause any further inflammatory response following peripheral nerve injury, suggesting the possibility of the chronic application of the sieve-type neural electrodes. This work was supported by the Basic Science Research Program funded by the Ministry of Science (2016R1D1A1B03933986), and by the convergence technology development program for bionic arm (2017M3C1B2085303).

Keywords: biocompatibility, motor functions, neural electrodes, peripheral nerve injury, sensory functions

Procedia PDF Downloads 114
269 Music as Source Domain: A Cross-Linguistic Exploration of Conceptual Metaphors

Authors: Eleanor Sweeney, Chunyuan Di

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The metaphors people use in everyday discourse do not arise randomly; rather, they develop from our physical experiences in our social and cultural environments. Conceptual Metaphor Theory (CMT) explains that through metaphor, we apply our embodied understanding of the physical world to non-material concepts to understand and express abstract concepts. Our most productive source domains derive from our embodied understanding and allow us to develop primary metaphors, and from primary metaphors, an elaborate, creative world of culturally constructed complex metaphors. Cognitive Linguistics researchers draw upon individual embodied experience for primary metaphors. Socioculturally embodied experience through music has long furnished linguistic expressions in diverse languages, as conceptual metaphors or everyday expressions.  Can a socially embodied experience function in the same way as an individually embodied experience in the creation of conceptual metaphors? The authors argue that since music is inherently social and embodied, musical experiences function as a richly motivated source domain. The focus of this study is socially embodied musical experience which is then reflected and expressed through metaphors. This cross-linguistic study explores music as a source domain for metaphors of social alignment in English, French, and Chinese. The authors explored two public discourse sites, Facebook and Linguée, in order to collect linguistic metaphors from three different languages. By conducting this cross-linguistic study, cross-cultural similarities and differences in metaphors for which music is the source domain can be examined. Different musical elements, such as melody, speed, rhythm and harmony, are analyzed for their possible metaphoric meanings of social alignment. Our findings suggest that the general metaphor cooperation is music is a productive metaphor with some subcases, and that correlated social behaviors can be metaphorically expressed with certain elements in music. For example, since performance is a subset of the category behavior, there is a natural mapping from performance in music to behavior in social settings: social alignment is musical performance. Musical performance entails a collective social expectation that exerts control over individual behavior.  When individual behavior does not align with the collective social expectation, music-related expressions are often used to express how the individual is violating social norms. Moreover, when individuals do align their behavior with social norms, similar musical expressions are used. Cooperation is a crucial social value in all cultures, indeed it is a key element of survival, and music provides a coherent, consistent, and rich source domain—one based upon a universal and definitive cultural practice.

Keywords: Chinese, Conceptual Metaphor Theory, cross-linguistic, culturally embodied experience, English, French, metaphor, music

Procedia PDF Downloads 133
268 The Porcine Reproductive and Respiratory Syndrome Virus Genotype 2 (PRRSV-2)-derived Oncolytic Protein Reprograms Tumor-Associated Macrophages

Authors: Farrah Putri Salmanida, Mei-Li Wu, Rika Wahyuningtyas, Wen-Bin Chung, Hso-Chi Chaung, Ko-Tung Chang

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Within the field of immunotherapy, oncolytic virotherapy (OVT) employs dual approaches that directly eliminate tumor cells while preserving healthy ones and indirectly reprogram the tumor microenvironment (TME) to elicit antitumor responses. Within the TME, tumor associated macrophages (TAMs) manifest characteristics akin to those of anti-inflammatory M2 macrophages, thus earning the designation of M2-like TAMs. In prior research, two antigens denoted as A1 (g6Ld10T) and A3 (ORF6L5), derived from a complete sequence of ORF5 with partial sequence of ORF6 in Porcine Reproductive and Respiratory Syndrome Virus Genotype 2 (PRRSV-2), demonstrated the capacity to repolarize M2-type porcine alveolar macrophages (PAMs) into M1 phenotypes. In this study, we sought for utilizing OVT strategies by introducing A1 or A3 on TAMs to endow them with the anti-tumor traits of M1 macrophages while retaining their capacity to target cancer cells. Upon exposing human THP-1-derived M2 macrophages to a cross-species test with 2 µg/ml of either A1 or A3 for 24 hours, real time PCR revealed that A3, but not A1, treated cells exhibited upregulated gene expressions of M1 markers (CCR7, IL-1ß, CCL2, Cox2, CD80). These cells reacted to virus-derived antigen, as evidenced by increased expression of pattern-recognition receptors TLR3, TLR7, and TLR9, subsequently providing feedback in the form of type I interferon responses like IFNAR1, IFN-ß, IRF3, IRF7, OAS1, Mx1, and ISG15. Through an MTT assay, only after 15 µg/ml of A3 treatment could the cell viability decrease, with a predicted IC50 of 16.96 µg/ml. Interestingly, A3 caused dose-dependent toxicity to a rat C6 glial cancer cell line even at doses as low as 2.5 µg/ml and reached its IC50 at 9.419 µg/ml. Using Annexin V/7AAD staining and PCR test, we deduced that a significant proportion of C6 cells were undergoing the early apoptosis phase predominantly through the intrinsic apoptosis cascade involving Bcl-2 family proteins. Following this stage, we conducted a test on A3’s repolarization ability, which revealed a significant rise in M1 gene expression markers, such as TNF, CD80, and IL-1ß, in M2-like TAMs generated in vitro from murine RAW264.7 macrophages grown with conditioned medium of 4T1 breast cancer cells. This was corroborated by the results of transcriptome analysis, which revealed that the primary subset among the top 10 to top 30 significantly upregulated differentially expressed genes (DEGs) dominantly consisted of M1 macrophages profiles, including Ccl3, Ccl4, Csf3, TNF, Bcl6b, Stc1, and Dusp2. Our findings unveiled the remarkable potential of the PRRSV-derived antigen A3 to repolarize macrophages while also being capable of selectively inducing apoptosis in cancerous cells. While further in vivo study is needed for A3, it holds promise as an adjuvant by its dual effects in cancer therapy modalities.

Keywords: cancer cell apoptosis, interferon responses, macrophage repolarization, recombinant protein

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267 Case Study of Human Factors and Ergonomics in the Design and Use of Harness-Embedded Costumes in the Entertainment Industry

Authors: Marielle Hanley, Brandon Takahashi, Gerry Hanley, Gabriella Hancock

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Safety harnesses and their protocols are very common within the construction industry, and the Occupational Safety and Health Administration has provided extensive guidelines with protocols being constantly updated to ensure the highest level of safety within construction sites. There is also extensive research on harnesses that are meant to keep people in place in moving vehicles, such as seatbelts. Though this research is comprehensive in these areas, the findings and recommendations are not generally applicable to other industry sectors where harnesses are used, such as the entertainment industry. The focus of this case study is on the design and use of harnesses used by theme park employees wearing elaborate costumes in parades and performances. The key factors of posture, kinesthetic factors, and harness engineering interact in significantly different ways when the user is performing repetitive choreography with 20 to 40 lbs. of apparatus connected to harnesses that need to be hidden from the audience’s view. Human factors and ergonomic analysis take into account the required performers’ behaviors, the physical and mental preparation and posture of the performer, the design of the harness-embedded costume, and the environmental conditions during the performance (e.g., wind) that can determine the physical stresses placed on the harness and performer. The uniqueness and expense of elaborate costumes frequently result in one or two costumes created for production, and a variety of different performers need to fit into the same costume. Consequently, the harnesses should be adjustable if they are to minimize the physical and cognitive loads on the performer, but they are frequently more a “one-size fits all”. The complexity of human and technology interactions produces a range of detrimental outcomes, from muscle strains to nerve damage, mental and physical fatigue, and reduced motivation to perform at peak levels. Based on observations conducted over four years for this case study, a number of recommendations to institutionalize the human factors and ergonomic analyses can significantly improve the safety, reliability, and quality of performances with harness-embedded costumes in the entertainment industry. Human factors and ergonomic analyses can be integrated into the engineering design of the performance costumes with embedded harnesses, the conditioning and training of the performers using the costumes, the choreography of the performances within the staged setting and the maintenance of the harness-embedded costumes. By applying human factors and ergonomic methodologies in the entertainment industry, the industry management and support staff can significantly reduce the risks of injury, improve the longevity of unique performers, increase the longevity of the harness-embedded costumes, and produce the desired entertainment value for audiences.

Keywords: ergonomics in entertainment industry, harness-embedded costumes, performer safety, injury prevention

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266 Investigating the Impact of Task Demand and Duration on Passage of Time Judgements and Duration Estimates

Authors: Jesika A. Walker, Mohammed Aswad, Guy Lacroix, Denis Cousineau

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There is a fundamental disconnect between the experience of time passing and the chronometric units by which time is quantified. Specifically, there appears to be no relationship between the passage of time judgments (PoTJs) and verbal duration estimates at short durations (e.g., < 2000 milliseconds). When a duration is longer than several minutes, however, evidence suggests that a slower feeling of time passing is predictive of overestimation. Might the length of a task moderate the relation between PoTJs and duration estimates? Similarly, the estimation paradigm (prospective vs. retrospective) and the mental effort demanded of a task (task demand) have both been found to influence duration estimates. However, only a handful of experiments have investigated these effects for tasks of long durations, and the results have been mixed. Thus, might the length of a task also moderate the effects of the estimation paradigm and task demand on duration estimates? To investigate these questions, 273 participants performed either an easy or difficult visual and memory search task for either eight or 58 minutes, under prospective or retrospective instructions. Afterward, participants provided a duration estimate in minutes, followed by a PoTJ on a Likert scale (1 = very slow, 7 = very fast). A 2 (prospective vs. retrospective) × 2 (eight minutes vs. 58 minutes) × 2 (high vs. low difficulty) between-subjects ANOVA revealed a two-way interaction between task demand and task duration on PoTJs, p = .02. Specifically, time felt faster in the more challenging task, but only in the eight-minute condition, p < .01. Duration estimates were transformed into RATIOs (estimate/actual duration) to standardize estimates across durations. An ANOVA revealed a two-way interaction between estimation paradigm and task duration, p = .03. Specifically, participants overestimated the task more if they were given prospective instructions, but only in the eight-minute task. Surprisingly, there was no effect of task difficulty on duration estimates. Thus, the demands of a task may influence ‘feeling of time’ and ‘estimation time’ differently, contributing to the existing theory that these two forms of time judgement rely on separate underlying cognitive mechanisms. Finally, a significant main effect of task duration was found for both PoTJs and duration estimates (ps < .001). Participants underestimated the 58-minute task (m = 42.5 minutes) and overestimated the eight-minute task (m = 10.7 minutes). Yet, they reported the 58-minute task as passing significantly slower on a Likert scale (m = 2.5) compared to the eight-minute task (m = 4.1). In fact, a significant correlation was found between PoTJ and duration estimation (r = .27, p <.001). This experiment thus provides evidence for a compensatory effect at longer durations, in which people underestimate a ‘slow feeling condition and overestimate a ‘fast feeling condition. The results are discussed in relation to heuristics that might alter the relationship between these two variables when conditions range from several minutes up to almost an hour.

Keywords: duration estimates, long durations, passage of time judgements, task demands

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265 Learning Academic Skills through Movement: A Case Study in Evaluation

Authors: Y. Salfati, D. Sharef Bussel, J. Zamir

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In this paper, we present an Evaluation Case Study implementing the eight principles of Collaborative Approaches to Evaluation (CAE) as designed by Brad Cousins in the past decade. The focus of this paper is sharing a rich experience in which we achieved two main goals. The first was the development of a valuable and meaningful new teacher training program, and the second was a successful implementation of the CAE principles. The innovative teacher training program is based on the idea of including physical movement during the process of teaching and learning academic themes. The program is called Learning through Movement. This program is a response to a call from the Ministry of Education, claiming that today children sit in front of screens and do not exercise any physical activity. In order to contribute to children’s health, physical, and cognitive development, the Ministry of Education promotes learning through physical activities. Research supports the idea that sports and physical exercise improve academic achievements. The Learning through Movement program is operated by Kaye Academic College. Students in the Elementary School Training Program, together with students in the Physical Education Training Program, implement the program in collaboration with two mentors from the College. The program combines academic learning with physical activity. The evaluation began at the beginning of the program. During the evaluation process, data was collected by means of qualitative tools, including interviews with mentors, observations during the students’ collaborative planning, class observations at school and focus groups with students, as well as the collection of documentation related to the teamwork and to the program itself. The data was analyzed using content analysis and triangulation. The preliminary results show outcomes relating to the Teacher Training Programs, the student teachers, the pupils in class, the role of Physical Education teachers, and the evaluation. The Teacher Training Programs developed a collaborative approach to lesson planning. The students' teachers demonstrated a change in their basic attitudes towards the idea of integrating physical activities during the lessons. The pupils indicated higher motivation through full participation in classes. These three outcomes are indicators of the success of the program. An additional significant outcome of the program relates to the status and role of the physical education teachers, changing their role from marginal to central in the school. Concerning evaluation, a deep sense of trust and confidence was achieved, between the evaluator and the whole team. The paper includes the perspectives and challenges of the heads and mentors of the two programs as well as the evaluator’s conclusions. The evaluation unveils challenges in conducting a CAE evaluation in such a complex setting.

Keywords: collaborative evaluation, training teachers, learning through movement

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264 The French Ekang Ethnographic Dictionary. The Quantum Approach

Authors: Henda Gnakate Biba, Ndassa Mouafon Issa

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Dictionaries modeled on the Western model [tonic accent languages] are not suitable and do not account for tonal languages phonologically, which is why the [prosodic and phonological] ethnographic dictionary was designed. It is a glossary that expresses the tones and the rhythm of words. It recreates exactly the speaking or singing of a tonal language, and allows the non-speaker of this language to pronounce the words as if they were a native. It is a dictionary adapted to tonal languages. It was built from ethnomusicological theorems and phonological processes, according to Jean. J. Rousseau 1776 hypothesis /To say and to sing were once the same thing/. Each word in the French dictionary finds its corresponding language, ekaη. And each word ekaη is written on a musical staff. This ethnographic dictionary is also an inventive, original and innovative research thesis, but it is also an inventive, original and innovative research thesis. A contribution to the theoretical, musicological, ethno musicological and linguistic conceptualization of languages, giving rise to the practice of interlocution between the social and cognitive sciences, the activities of artistic creation and the question of modeling in the human sciences: mathematics, computer science, translation automation and artificial intelligence. When you apply this theory to any text of a folksong of a world-tone language, you do not only piece together the exact melody, rhythm, and harmonies of that song as if you knew it in advance but also the exact speaking of this language. The author believes that the issue of the disappearance of tonal languages and their preservation has been structurally resolved, as well as one of the greatest cultural equations related to the composition and creation of tonal, polytonal and random music. The experimentation confirming the theorization designed a semi-digital, semi-analog application which translates the tonal languages of Africa (about 2,100 languages) into blues, jazz, world music, polyphonic music, tonal and anatonal music and deterministic and random music). To test this application, I use a music reading and writing software that allows me to collect the data extracted from my mother tongue, which is already modeled in the musical staves saved in the ethnographic (semiotic) dictionary for automatic translation ( volume 2 of the book). Translation is done (from writing to writing, from writing to speech and from writing to music). Mode of operation: you type a text on your computer, a structured song (chorus-verse), and you command the machine a melody of blues, jazz and, world music or, variety etc. The software runs, giving you the option to choose harmonies, and then you select your melody.

Keywords: music, language, entenglement, science, research

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263 Mental Health and Secondary Trauma in Service Providers Working with Refugees

Authors: Marko Živanović, Jovana Bjekić, Maša Vukčević Marković

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Professionals and volunteers involved in refugee protection and support are on a daily basis faced with people who have experienced numerous traumatic experiences and, as such, are subjected to secondary traumatization (ST). The aim of this study was to provide insight into risk factors for ST in helpers working with refugees in Serbia. A total of 175 participants working with refugees fulfilled: Secondary Traumatization Questionnaire, checklist of refugees’ traumatic experiences, Hopkins Symptoms Checklist (HSCL) assessing depression and anxiety symptoms, quality of life questionnaire (MANSA), HEXACO personality inventory, and COPE assessing coping mechanisms. In addition, participants provided information on work-related problems. Qualitative analysis of answers to the question about most difficult part of their job has shown that burnout-related issues are clustered around three recurrent topics that can be considered as the most prominent generators of stress, namely: ‘lack of organization and cooperation’, ‘not been able to do enough’, and ‘hard to take it and to process it’. Factor analysis (Maximum likelihood extraction, Promax rotation) have shown that ST comprises of two correlated factors (r = .533, p < .01), namely Psychological deficits and Intrusions. Results have shown that risk factor for ST could be find in three interrelated sources: 1) work-related problems; 2) personality-related risk factors and 3) clients’ traumatic experiences. Among personality related factors, it was shown that risk factor for Intrusions could be find in – high Emotionality (β = .221, p < .05), and Altruism (β = .322, p < .01), while low Extraversion (β = -.365, p < .01) represents risk factor for Psychological deficits. In addition, usage of maladaptive coping mechanisms –mental disengagement (r = .253, p < .01), behavioral disengagement (r = .274, p < .01), focusing on distress and venting of emotions (r = .220, p < .05), denial (r = .164, p < .05), and substance use (r = .232, p < .01) correlate with Psychological deficits while Intrusions corelate with Mental disengagement (r = .251, p < .01) and denial (r = .183, p < .05). Regarding clients’ traumatic experiences it was shown that both quantity of traumatic events in country of origin (for Deficits r = .226, p < .01; for Intrusions r = .174, p < .05) and in transit (for Deficits r = .288, p < .01), as well as certain content-related features of such experiences (especially experiences which are severely dislocated from ‘everyday reality’) are related to ST. In addition, Psychological deficits and Intrusions have shown to be accompanied by symptoms of depression (r = .760, p < .01; r = .552, p < .01) and anxiety (r = .740, p < .01; r = .447, p < .01) and overall lower life quality (r = -.454, p < .01; r = .256, p < .01). Results indicate that psychological vulnerability of persons who are working with traumatized individuals can be found in certain personality traits, and usage of maladaptive coping mechanisms, which disable one to deal with work-related issues, and to cope with quantity and quality of traumatic experiences they were faced with, affecting ones’ psychological well-being. Acknowledgement: This research was funded by IRC Serbia.

Keywords: mental health, refugees, secondary traumatization, traumatic experiences

Procedia PDF Downloads 203
262 TNF Modulation of Cancer Stem Cells in Renal Clear Cell Carcinoma

Authors: Rafia S. Al-lamki, Jun Wang, Simon Pacey, Jordan Pober, John R. Bradley

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Tumor necrosis factor alpha (TNF), signaling through TNFR2, may act an autocrine growth factor for renal tubular epithelial cells. Clear cell renal carcinomas (ccRCC) contain cancer stem cells (CSCs) that give rise to progeny which form the bulk of the tumor. CSCs are rarely in cell cycle and, as non-proliferating cells, resist most chemotherapeutic agents. Thus, recurrence after chemotherapy may result from the survival of CSCs. Therapeutic targeting of both CSCs and the more differentiated bulk tumor populations may provide a more effective strategy for treatment of RCC. In this study, we hypothesized that TNFR2 signaling will induce CSCs in ccRCC to enter cell cycle so that treatment with ligands that engage TNFR2 will render CSCs susceptible to chemotherapy. To test this hypothesis, we have utilized wild-type TNF (wtTNF) or specific muteins selective for TNFR1 (R1TNF) or TNFR2 (R2TNF) to treat either short-term organ cultures of ccRCC and adjacent normal kidney (NK) tissue or cultures of CD133+ cells isolated from ccRCC and adjacent NK, hereafter referred to as stem cell-like cells (SCLCs). The effect of cyclophosphamide (CP), currently an effective anticancer agent, was tested on CD133+SCLCs from ccRCC and NK before and after R2TNF treatment. Responses to TNF were assessed by flow cytometry (FACS), immunofluorescence, and quantitative real-time PCR, TUNEL, and cell viability assays. Cytotoxic effect of CP was analyzed by Annexin V and propidium iodide staining with FACS. In addition, we assessed the effect of TNF on isolated SCLCs differentiation using a three-dimensional (3D) culture system. Clinical samples of ccRCC contain a greater number SCLCs compared to NK and the number of SCSC increases with higher tumor grade. Isolated SCLCs show expression of stemness markers (oct4, Nanog, Sox2, Lin28) but not differentiation markers (cytokeratin, CD31, CD45, and EpCAM). In ccRCC organ cultures, wtTNF and R2TNF increase CD133 and TNFR2 expression and promote cell cycle entry whereas wtTNF and R1TNF increase TNFR1 expression and promote cell death of SCLCs. Similar findings are observed in SCLCs isolated from NK but the effect was greater in SCLCs isolated from ccRCC. Application of CP distinctly triggered apoptotic and necrotic cell death in SLCSs pre-treatment with R2TNF as compared to CP treatment alone, with SCLCs from ccRCC more sensitive to CP compared to SLCS from NK. Furthermore, TNF promotes differentiation of SCLCs to an epithelial phenotype in 3D cultures, confirmed by cytokeratin expression and loss of stemness markers Nanog and Sox2. The differentiated cells show positive expression of TNF and TNFR2. These findings provide evidence that selective engagement of TNFR2 drive CSCs to cell proliferation/differentiation, and targeting of cycling cells with TNFR2 agonist in combination with anti-cancer agents may be a potential therapy for RCC.

Keywords: cancer stem cells, ccRCC, cell cycle, cell death, TNF, TNFR1, TNFR2, CD133

Procedia PDF Downloads 241