Search results for: Eliza Bramwell
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 15

Search results for: Eliza Bramwell

15 Teaching How to Speak ‘Correct’ English in No Time: An Assessment of the ‘Success’ of Professor Higgins’ Motivation in George Bernard Shaw’s Pygmalion

Authors: Armel Mbon

Abstract:

This paper examines the ‘success’ of George Bernard Shaw's main character Professor Higgins' motivation in teaching Eliza Doolittle, a young Cockney flower girl, how to speak 'correct' English in no time in Pygmalion. Notice should be given that Shaw in whose writings, language issues feature prominently, does not believe there is such a thing as perfectly correct English, but believes in the varieties of spoken English as a source of its richness. Indeed, along with his fellow phonetician Colonel Pickering, Henry Higgins succeeds in teaching Eliza that he first judges unfairly, the dialect of the upper classes and Received Pronunciation, to facilitate her social advancement. So, after six months of rigorous learning, Eliza's speech and manners are transformed, and she is able to pass herself off as a lady. Such is the success of Professor Higgins’ motivation in linguistically transforming his learner in record time. On the other side, his motivation is unsuccessful since, by the end of the play, he cannot have Eliza he believes he has shaped to his so-called good image, for wife. So, this paper aims to show, in support of the psychological approach, that in motivation, feelings, pride and prejudice cannot be combined, and that one has not to pre-judge someone’s attitude based purely on how well they speak English.

Keywords: teaching, speak, in no time, success

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14 Communication and Management of Incidental Pathology in a Cohort of 1,214 Consecutive Appendicectomies

Authors: Matheesha Herath, Ned Kinnear, Bridget Heijkoop, Eliza Bramwell, Alannah Frazetto, Amy Noll, Prajay Patel, Derek Hennessey, Greg Otto, Christopher Dobbins, Tarik Sammour, James Moore

Abstract:

Background: Important incidental pathology requiring further action is commonly found during appendicectomy, macro- and microscopically. It is unknown whether the acute surgical unit (ASU) model affects the management and disclosure of these findings. Methods: An ASU model was introduced at our institution on 01/08/2012. In this retrospective cohort study, all patients undergoing appendicectomy 2.5 years before (traditional group) or after (ASU group) this date were compared. The primary outcomes were rates of appropriate management of the incidental findings and communication of the findings to the patient and to their general practitioner (GP). Results: 1,214 patients underwent emergency appendicectomy; 465 in the traditional group and 749 in the ASU group. 80 (6.6%) patients (25 and 55 in each respective period) had important incidental findings. There were 24 patients with benign polyps, 15 with neuro-endocrine tumour, 11 with endometriosis, 8 with pelvic inflammatory disease, 8 Enterobius vermicularis infection, 7 with low grade mucinous cystadenoma, 3 with inflammatory bowel disease, 2 with diverticulitis, 2 with tubo-ovarian mass, 1 with secondary appendiceal malignancy and none with primary appendiceal adenocarcinoma. One patient had dual pathologies. There was no difference between the traditional and ASU group with regards to communication of the findings to the patient (p=0.44) and their GP (p=0.27), and there was no difference in the rates of appropriate management (p=0.21). Conclusions: The introduction of an ASU model did not change rates of surgeon-to-patient and surgeon-to-GP communication nor affect rates of appropriate management of important incidental pathology during an appendectomy.

Keywords: acute care surgery, appendicitis, appendicectomy, incidental

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13 More than Words: Literature Review of Sexual Culture for People Who are Deaf

Authors: Eliza F. Dunn

Abstract:

Scripts are a hypothetical outline or roadmap to life as defined by culture. Sexual scripts are similarly a roadmap for what to expect in dating and sexual experiences. The articles for this review were found by searching three databases and refining 621 articles to 13 that are used in the results section. Some ways deaf sexual scripts vary from Traditional Sexual Scripts (TSS) are in the areas of gendered roles and sexual themes, which were both absent in deaf sexual scripts. Theories for why these differences exist are explored: the presence or absence of sexual education or the effects of intimate partner violence due to being a part of a disabled community. Finally, unique sexual flourishing for people who are d/Deaf found in studies was discussed, suggesting the needed perspective of resilience to be a focus of future research to fully understand deaf sexual scripts. Future research is discussed, noting the need for defining aspects of deaf sexual scripts in detail and studying the differences between these scripts and the TSS.

Keywords: deaf, deafness, sexual scripts, lift scripts, sexual flourishing

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12 Play in College: Shifting Perspectives and Creative Problem-Based Play

Authors: Agni Stylianou-Georgiou, Eliza Pitri

Abstract:

This study is a design narrative that discusses researchers’ new learning based on changes made in pedagogies and learning opportunities in the context of a Cognitive Psychology and an Art History undergraduate course. The purpose of this study was to investigate how to encourage creative problem-based play in tertiary education engaging instructors and student-teachers in designing educational games. Course instructors modified content to encourage flexible thinking during game design problem-solving. Qualitative analyses of data sources indicated that Thinking Birds’ questions could encourage flexible thinking as instructors engaged in creative problem-based play. However, student-teachers demonstrated weakness in adopting flexible thinking during game design problem solving. Further studies of student-teachers’ shifting perspectives during different instructional design tasks would provide insights for developing the Thinking Birds’ questions as tools for creative problem solving.

Keywords: creative problem-based play, educational games, flexible thinking, tertiary education

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11 Waste Identification Diagrams Effectiveness: A Case Study in the Manaus Industrial Pole

Authors: José Dinis-Carvalho, Levi Guimarães, Celina Leão, Rui Sousa, Rosa Eliza Vieira, Larissa Thomaz, Kelliane Guerreiro

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This research paper investigates the efficacy of waste identification diagrams (WIDs) as a tool for waste reduction and management within the Manaus Industrial Pole. The study focuses on assessing the practical application and effectiveness of WIDs in identifying, categorizing, and mitigating various forms of waste generated across industrial processes. Employing a mixed-methods approach, including a qualitative questionnaire applied to 5 companies and quantitative data analysis with SPSS statistical software, the research evaluates the implementation and impact of WIDs on waste reduction practices in select industries within the Manaus Industrial Pole. The findings contribute to understanding the utility of WIDs as a proactive strategy for waste management, offering insights into their potential for fostering sustainable practices and promoting environmental stewardship in industrial settings. The study also discusses challenges, best practices, and recommendations for optimizing the utilization of WIDs in industrial waste management, thereby addressing the broader implications for sustainable industrial development.

Keywords: waste identification diagram, value stream mapping, overall equipment effectiveness, lean manufacturing

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10 Motivational Antecedents that Influenced a Higher Education Institution in the Philippines to Adopt Enterprise Architecture

Authors: Ma. Eliza Jijeth V. dela Cruz

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Technology is a recent prodigy in people’s everyday life that has taken off. It infiltrated almost every aspect of one’s lives, changing how people work, how people learn and how people perceive things. Academic Institutions, just like other organizations, have deeply modified its strategies to integrate technology into the institutional vision and corporate strategy that has never been greater. Information and Communications Technology (ICT) continues to be recognized as a major factor in organizations realizing its aims and objectives. Consequently, ICT has an important role in the mobilization of an academic institution’s strategy to support the delivery of operational, strategic or transformational objectives. This ICT strategy should align the institution with the radical changes of the ICT world through the use of Enterprise Architecture (EA). Hence, EA’s objective is to optimize the islands of legacy processes to be integrated that is receptive to change and supportive of the delivery of the strategy. In this paper, the focus is to explore the motivational antecedents during the adoption of EA in a Higher Education Institution in the Philippines for its ICT strategic plan. The seven antecedents (viewpoint, stakeholders, human traits, vision, revolutionary innovation, techniques and change components) provide understanding into EA adoption and the antecedents that influences the process of EA adoption.

Keywords: Enterprise Architecture, Adoption, Antecedents, Higher Educational Institutions

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9 Chatbots as Language Teaching Tools for L2 English Learners

Authors: Feiying Wu

Abstract:

Chatbots are computer programs that attempt to engage a human in a dialogue, which originated in the 1960s with MIT's Eliza. However, they have become widespread more recently as advances in language technology have produced chatbots with increasing linguistic quality and sophistication, leading to their potential to serve as a tool for Computer-Assisted Language Learning(CALL). The aim of this article is to assess the feasibility of using two chatbots, Mitsuku and CleverBot, as pedagogical tools for learning English as a second language by stimulating L2 learners with distinct English proficiencies. Speaking of the input of stimulated learners, they are measured by AntWordProfiler to match the user's expected vocabulary proficiency. Totally, there are four chat sessions as each chatbot will converse with both beginners and advanced learners. For evaluation, it focuses on chatbots' responses from a linguistic standpoint, encompassing vocabulary and sentence levels. The vocabulary level is determined by the vocabulary range and the reaction to misspelled words. Grammatical accuracy and responsiveness to poorly formed sentences are assessed for the sentence level. In addition, the assessment of this essay sets 25% lexical and grammatical incorrect input to determine chatbots' corrective ability towards different linguistic forms. Based on statistical evidence and illustration of examples, despite the small sample size, neither Mitsuku nor CleverBot is ideal as educational tools based on their performance through word range, grammatical accuracy, topic range, and corrective feedback for incorrect words and sentences, but rather as a conversational tool for beginners of L2 English.

Keywords: chatbots, CALL, L2, corrective feedback

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8 Landcover Mapping Using Lidar Data and Aerial Image and Soil Fertility Degradation Assessment for Rice Production Area in Quezon, Nueva Ecija, Philippines

Authors: Eliza. E. Camaso, Guiller. B. Damian, Miguelito. F. Isip, Ronaldo T. Alberto

Abstract:

Land-cover maps were important for many scientific, ecological and land management purposes and during the last decades, rapid decrease of soil fertility was observed to be due to land use practices such as rice cultivation. High-precision land-cover maps are not yet available in the area which is important in an economy management. To assure   accurate mapping of land cover to provide information, remote sensing is a very suitable tool to carry out this task and automatic land use and cover detection. The study did not only provide high precision land cover maps but it also provides estimates of rice production area that had undergone chemical degradation due to fertility decline. Land-cover were delineated and classified into pre-defined classes to achieve proper detection features. After generation of Land-cover map, of high intensity of rice cultivation, soil fertility degradation assessment in rice production area due to fertility decline was created to assess the impact of soils used in agricultural production. Using Simple spatial analysis functions and ArcGIS, the Land-cover map of Municipality of Quezon in Nueva Ecija, Philippines was overlaid to the fertility decline maps from Land Degradation Assessment Philippines- Bureau of Soils and Water Management (LADA-Philippines-BSWM) to determine the area of rice crops that were most likely where nitrogen, phosphorus, zinc and sulfur deficiencies were induced by high dosage of urea and imbalance N:P fertilization. The result found out that 80.00 % of fallow and 99.81% of rice production area has high soil fertility decline.

Keywords: aerial image, landcover, LiDAR, soil fertility degradation

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7 Assessing the Financial Impact of Federal Benefit Program Enrollment on Low-income Households

Authors: Timothy Scheinert, Eliza Wright

Abstract:

Background: Link Health is a Boston-based non-profit leveraging in-person and digital platforms to promote health equity. Its primary aim is to financially support low-income individuals through enrollment in federal benefit programs. This study examines the monetary impact of enrollment in several benefit programs. Methodologies: Approximately 17,000 individuals have been screened for eligibility via digital outreach, community events, and in-person clinics. Enrollment and financial distributions are evaluated across programs, including the Affordable Connectivity Program (ACP), Lifeline, LIHEAP, Transitional Aid to Families with Dependent Children (TAFDC), and the Supplemental Nutrition Assistance Program (SNAP). Major Findings: A total of 1,895 individuals have successfully applied, collectively distributing an estimated $1,288,152.00 in aid. The largest contributors to this sum include: ACP: 1,149 enrollments, $413,640 distributed annually. Child Care Financial Assistance (CCFA): 15 enrollments, $240,000 distributed annually. Lifeline: 602 enrollments, $66,822 distributed annually. LIHEAP: 25 enrollments, $48,750 distributed annually. SNAP: 41 enrollments, $123,000 distributed annually. TAFDC: 21 enrollments, $341,760 distributed annually. Conclusions: These results highlight the role of targeted outreach and effective enrollment processes in promoting access to federal benefit programs. High enrollment rates in ACP and Lifeline demonstrate a considerable need for affordable broadband and internet services. Programs like CCFA and TAFDC, despite lower enrollment numbers, provide sizable support per individual. This analysis advocates for continued funding of federal benefit programs. Future efforts can be made to develop screening tools that identify eligibility for multiple programs and reduce the complexity of enrollment.

Keywords: benefits, childcare, connectivity, equity, nutrition

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6 Extraction of Forest Plantation Resources in Selected Forest of San Manuel, Pangasinan, Philippines Using LiDAR Data for Forest Status Assessment

Authors: Mark Joseph Quinto, Roan Beronilla, Guiller Damian, Eliza Camaso, Ronaldo Alberto

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Forest inventories are essential to assess the composition, structure and distribution of forest vegetation that can be used as baseline information for management decisions. Classical forest inventory is labor intensive and time-consuming and sometimes even dangerous. The use of Light Detection and Ranging (LiDAR) in forest inventory would improve and overcome these restrictions. This study was conducted to determine the possibility of using LiDAR derived data in extracting high accuracy forest biophysical parameters and as a non-destructive method for forest status analysis of San Manual, Pangasinan. Forest resources extraction was carried out using LAS tools, GIS, Envi and .bat scripts with the available LiDAR data. The process includes the generation of derivatives such as Digital Terrain Model (DTM), Canopy Height Model (CHM) and Canopy Cover Model (CCM) in .bat scripts followed by the generation of 17 composite bands to be used in the extraction of forest classification covers using ENVI 4.8 and GIS software. The Diameter in Breast Height (DBH), Above Ground Biomass (AGB) and Carbon Stock (CS) were estimated for each classified forest cover and Tree Count Extraction was carried out using GIS. Subsequently, field validation was conducted for accuracy assessment. Results showed that the forest of San Manuel has 73% Forest Cover, which is relatively much higher as compared to the 10% canopy cover requirement. On the extracted canopy height, 80% of the tree’s height ranges from 12 m to 17 m. CS of the three forest covers based on the AGB were: 20819.59 kg/20x20 m for closed broadleaf, 8609.82 kg/20x20 m for broadleaf plantation and 15545.57 kg/20x20m for open broadleaf. Average tree counts for the tree forest plantation was 413 trees/ha. As such, the forest of San Manuel has high percent forest cover and high CS.

Keywords: carbon stock, forest inventory, LiDAR, tree count

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5 Effect of Yeast Selenium on CD4 T Cell and WAZ of HIV1 Positive Children in Nyamasaria in Kisumu Kenya

Authors: S. B. Otieno1, F. Were, A. Afullo, K. Waza

Abstract:

Background: Multi drug resistance HIV has emerged rendering the current conventional treatment of HIV ineffective. There is a need for new treatment regime which is cheap, effective and not prone to resistance development by HIV. Methods: In randomized clinical study of 68 HIV positive children 3 – 15 years to asses the efficacy of yeast selenium in HIV/AIDS patients, 50μ yeast selenium was administered to 34 children while in matched control of 34 were put on placebo. Blood samples and weight of the both groups which were taken every 3 months intervals up to 6 months, were analyzed by ELIZA for CD4T cells, the data was analyzed by SPSS version 16, WAZ scores were analyzed by Epi Info version 6. Results: No significant difference in age { χ2 (1, 62) =0.03, p =0.853}, cause of morbidity between test and controls {χ2 (1, 65) = 5.87, p= 0.015} and on condition of foster parents {χ2 ( 1,63) = 5.57, p= 0.0172} was observed. Children on selenium showed progressive improvement of WAZ and significant difference at six months {F (5,12) = =5.758, P=0.006}, and weight gain of up to 4.1 kilograms in six months, and significant CD4 T cell count increase t= -2.943, p<0.05 compared to matched controls t = -1.258 p> 0.05. CD4 T cell count increased among all age groups on test 3-5 years (+ 267.1),5-8 years (+200.3) 9-15 years (+71.2) cells/mm3 and in matched controls a decrease 3-5 years (-71), 5-8 years (-125) and 9-13 years (-10.1) cells/mm3 . No significant difference inCD4 T cell count between boys {F (2, 32) = 1.531 p= 0.232} and between boys {F (2, 49) = 1.040, p= 0.361} on test and between boys and girls {F (5, 81) = 1.379, p= 0.241} on test. Similarly no significant difference between boys and girls were observed {F (5, 86) = 1.168, p= 0.332}.In the test group there was significant positive correlation β =252.23 between weight for age (WAZ), and CD4 T Cell Count p=0.007, R2= 0.252, F< 0.05. In matched controls no significant correlation between weight gain and CD4 T cell count change was observed at six months p > 0.05. No positive correlation β =-138.23 was observed between CD4T Cell count, WAZ, p=0.934, R2 =0.0337 F >0.05. Majority (96.78%) of children on test either remained or progressed to WHO immunological stage I. Conclusion: From this study it can be concluded that yeast Selenium is effective in slowing the progress of HIV 1 in children from WHO clinical stage I by improving CD4 T cell count and hence the immunity.

Keywords: selenium, HIV, AIDS, WAZ

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4 Evaluation on the Compliance of Essential Intrapartum Newborn Care among Nurses in Selected Government Hospital in Manila

Authors: Eliza Torrigue, Efrelyn Iellamo

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Maternal death is one of the rising health issues in the Philippines. It is alarming to know that in every hour of each day, a mother gives birth to a child who may not live to see the next day. Statistics shows that intrapartum period and third stage of labor are the very crucial periods for the expectant mother, as well as the first six hours of life for the newborn. To address the issue, The Essential Intrapartum Newborn Care (EINC) was developed. Through this, Obstetric Delivery Room (OB-DR) Nurses shall be updated with the evidence-based maternal and newborn care to ensure patient safety, thus, reducing maternal and child mortality. This study aims to describe the compliance of hospitals, especially of OB-DR nurses, to the EINC Protocols. The researcher aims to link the profile variables of the respondents in terms of age, length of service and formal training to their compliance on the EINC Protocols. The outcome of the study is geared towards the development of appropriate training program for OB-DR Nurses assigned in the delivery room of the hospitals based on the study’s results to sustain the EINC standards. A descriptive correlational method was used. The sample consists of 75 Obstetric Delivery Room (OB-DR) Nurses from three government hospitals in the City of Manila namely, Ospital ng Maynila Medical Center, Tondo Medical Center, and Gat Andres Bonifacio Memorial Medical Center. Data were collected using an evaluative checklist. Ranking, weighted mean, Chi-square and Pearson’s R were used to analyze data. The level of compliance to the EINC Protocols by the respondents was evaluated with an overall mean score of 4.768 implying that OB-DR Nurses have a high regard in complying with the step by step procedure of the EINC. Furthermore, data shows that formal training on EINC have a significant relationship with OB-DR Nurses’ level of compliance during cord care, AMTSL, and immediate newborn care until the first ninety minutes to six hours of life. However, the respondents’ age and length of service do not have a significant relationship with the compliance of OB-DR Nurses on EINC Protocols. In the pursuit of decreasing the maternal mortality in the Philippines, EINC Protocols have been widely implemented in the country especially in the government hospitals where most of the deliveries happen. In this study, it was found out that OB-DR Nurses adhere and are highly compliant to the standards in order to assure that optimum level of care is delivered to the mother and newborn. Formal training on EINC, on the other hand, create the most impact on the compliance of nurses. It is therefore recommended that there must be a structured enhancement training program to plan, implement and evaluate the EINC protocols in these government hospitals.

Keywords: compliance, intrapartum, newborn care, nurses

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3 An Adaptable Semi-Numerical Anisotropic Hyperelastic Model for the Simulation of High Pressure Forming

Authors: Daniel Tscharnuter, Eliza Truszkiewicz, Gerald Pinter

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High-quality surfaces of plastic parts can be achieved in a very cost-effective manner using in-mold processes, where e.g. scratch resistant or high gloss polymer films are pre-formed and subsequently receive their support structure by injection molding. The pre-forming may be done by high-pressure forming. In this process, a polymer sheet is heated and subsequently formed into the mold by pressurized air. Due to the heat transfer to the cooled mold the polymer temperature drops below its glass transition temperature. This ensures that the deformed microstructure is retained after depressurizing, giving the sheet its final formed shape. The development of a forming process relies heavily on the experience of engineers and trial-and-error procedures. Repeated mold design and testing cycles are however both time- and cost-intensive. It is, therefore, desirable to study the process using reliable computer simulations. Through simulations, the construction of the mold and the effect of various process parameters, e.g. temperature levels, non-uniform heating or timing and magnitude of pressure, on the deformation of the polymer sheet can be analyzed. Detailed knowledge of the deformation is particularly important in the forming of polymer films with integrated electro-optical functions. Care must be taken in the placement of devices, sensors and electrical and optical paths, which are far more sensitive to deformation than the polymers. Reliable numerical prediction of the deformation of the polymer sheets requires sophisticated material models. Polymer films are often either transversely isotropic or orthotropic due to molecular orientations induced during manufacturing. The anisotropic behavior affects the resulting strain field in the deformed film. For example, parts of the same shape but different strain fields may be created by varying the orientation of the film with respect to the mold. The numerical simulation of the high-pressure forming of such films thus requires material models that can capture the nonlinear anisotropic mechanical behavior. There are numerous commercial polymer grades for the engineers to choose from when developing a new part. The effort required for comprehensive material characterization may be prohibitive, especially when several materials are candidates for a specific application. We, therefore, propose a class of models for compressible hyperelasticity, which may be determined from basic experimental data and which can capture key features of the mechanical response. Invariant-based hyperelastic models with a reduced number of invariants are formulated in a semi-numerical way, such that the models are determined from a single uniaxial tensile tests for isotropic materials, or two tensile tests in the principal directions for transversely isotropic or orthotropic materials. The simulation of the high pressure forming of an orthotropic polymer film is finally done using an orthotropic formulation of the hyperelastic model.

Keywords: hyperelastic, anisotropic, polymer film, thermoforming

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2 Teacher Training for Bilingual Education of Deaf Students in Brazil

Authors: Mara Aparecida De Castilho Lopes. Maria Eliza Mattosinho Bernardes

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The education of deaf individuals in Brazil is grounded in the bilingual approach, which presupposes Brazilian Sign Language (Libras) as the first language for these students. In this perspective, Portuguese should be taught as a second language in its written form, ensuring that deaf students also have access to various academic subjects in sign language. Brazilian legislation (Federal Decree No. 5626 of 2005) mandates the teaching of Brazilian Sign Language in university teacher training programs, but there is no pre-established minimum workload. As a result, there is a significant disparity in the teaching and quality of teacher education across the Brazilian territory. Added to this fact is the general lack of awareness within society regarding the linguistic status of Libras, leading to a shortage of competent teachers for its use and instruction, particularly in higher education. Recently, Federal Law No. 14191 of 2021 established bilingual education for the deaf as a mode of instruction, indicating the need for adjustments in teacher training within higher education teacher preparation programs. Given this context, the objective of the present study was to analyze the teaching proposals for Brazilian Sign Language for students in teacher training programs at public universities in Brazil, presenting alternatives to overcome the current models and academic pathways of teaching and learning. In addition to analyzing Brazilian teaching models, an analysis of a continuing education model for teachers in a French institution was also conducted - considering the historical Franco-Brazilian path of deaf education in Brazil. The analysis of the current teacher training model for deaf education in Brazil revealed that initial exposure to sign language and its linguistic structure is not sufficient to provide future teachers with opportunities to reflect on bilingual teaching methods and practices, as seen in other definitions of bilingualism - bilingual education for proficient listeners in two oral languages. As a result, a training proposal was developed for an experimental interdisciplinary course, integrating the curriculum of an initial and continuing teacher training program alongside the Alfredo Bossi Chair at the University of São Paulo. This proposal is structured into three disciplines, which constitute consecutive moments in teacher education: Fundamental Aspects of Brazilian Sign Language, Bilingual Teaching Methodology, and Teaching Investigation Project - interdisciplinary engagement in the field of deafness. The last offered discipline represents an interdisciplinary supervised internship proposal, considering the multi-professional context that constitutes deaf education within a bilingual approach. In interdisciplinary work within the field of deafness, dialogue between teachers and other professionals who work with deaf students from different perspectives - teachers, speech therapists, and sign language interpreters - is frequently necessary. Through alternative avenues, these actions aim to direct the linguistic development of deaf students within their learning processes. Based on the innovative curriculum proposal described here, the intention is to contribute to the enhancement of teacher education in Brazil, with the goal of ensuring bilingual education for deaf students.

Keywords: bilingual education, teacher training, historical-cultural approach, interdisciplinary education, inclusive education

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1 Transcriptional Differences in B cell Subpopulations over the Course of Preclinical Autoimmunity Development

Authors: Aleksandra Bylinska, Samantha Slight-Webb, Kevin Thomas, Miles Smith, Susan Macwana, Nicolas Dominguez, Eliza Chakravarty, Joan T. Merrill, Judith A. James, Joel M. Guthridge

Abstract:

Background: Systemic Lupus Erythematosus (SLE) is an interferon-related autoimmune disease characterized by B cell dysfunction. One of the main hallmarks is a loss of tolerance to self-antigens leading to increased levels of autoantibodies against nuclear components (ANAs). However, up to 20% of healthy ANA+ individuals will not develop clinical illness. SLE is more prevalent among women and minority populations (African, Asian American and Hispanics). Moreover, African Americans have a stronger interferon (IFN) signature and develop more severe symptoms. The exact mechanisms involved in ethnicity-dependent B cell dysregulation and the progression of autoimmune disease from ANA+ healthy individuals to clinical disease remains unclear. Methods: Peripheral blood mononuclear cells (PBMCs) from African (AA) and European American (EA) ANA- (n=12), ANA+ (n=12) and SLE (n=12) individuals were assessed by multimodal scRNA-Seq/CITE-Seq methods to examine differential gene signatures in specific B cell subsets. Library preparation was done with a 10X Genomics Chromium according to established protocols and sequenced on Illumina NextSeq. The data were further analyzed for distinct cluster identification and differential gene signatures in the Seurat package in R and pathways analysis was performed using Ingenuity Pathways Analysis (IPA). Results: Comparing all subjects, 14 distinct B cell clusters were identified using a community detection algorithm and visualized with Uniform Manifold Approximation Projection (UMAP). The proportion of each of those clusters varied by disease status and ethnicity. Transitional B cells trended higher in ANA+ healthy individuals, especially in AA. Ribonucleoprotein high population (HNRNPH1 elevated, heterogeneous nuclear ribonucleoprotein, RNP-Hi) of proliferating Naïve B cells were more prevalent in SLE patients, specifically in EA. Interferon-induced protein high population (IFIT-Hi) of Naive B cells are increased in EA ANA- individuals. The proportion of memory B cells and plasma cells clusters tend to be expanded in SLE patients. As anticipated, we observed a higher signature of cytokine-related pathways, especially interferon, in SLE individuals. Pathway analysis among AA individuals revealed an NRF2-mediated Oxidative Stress response signature in the transitional B cell cluster, not seen in EA individuals. TNFR1/2 and Sirtuin Signaling pathway genes were higher in AA IFIT-Hi Naive B cells, whereas they were not detected in EA individuals. Interferon signaling was observed in B cells in both ethnicities. Oxidative phosphorylation was found in age-related B cells (ABCs) for both ethnicities, whereas Death Receptor Signaling was found only in EA patients in these cells. Interferon-related transcription factors were elevated in ABCs and IFIT-Hi Naive B cells in SLE subjects of both ethnicities. Conclusions: ANA+ healthy individuals have altered gene expression pathways in B cells that might drive apoptosis and subsequent clinical autoimmune pathogenesis. Increases in certain regulatory pathways may delay progression to SLE. Further, AA individuals have more elevated activation pathways that may make them more susceptible to SLE.

Keywords:

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