Search results for: real life contexts
9594 Personality, Coping, Quality of Life, and Distress in Persons with Hearing Loss: A Cross-Sectional Study of Patients Referred to an Audiological Service
Authors: Oyvind Nordvik, Peder O. L. Heggdal, Jonas Brannstrom, Flemming Vassbotn, Anne Kari Aarstad, Hans Jorgen Aarstad
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Background: Hearing Loss (HL) is a condition that may affect people in all stages of life, but the prevalence increases with age, mostly because of age-related HL, generally referred to as presbyacusis. As human speech is related to relatively high frequencies, even a limited hearing loss at high frequencies may cause impaired speech intelligibility. Being diagnosed with, treated for and living with a chronic condition such as HL, must for many be a disabling and stressful condition that put ones coping resources to test. Stress is a natural part of life and most people will experience stressful events or periods. Chronic diseases, such as HL, are risk factor for distress in individuals, causing anxiety and lowered mood. How an individual cope with HL may be closely connected to the level of distress he or she is experiencing and to personality, which can be defined as those characteristics of a person that account for consistent patterns of feelings, thinking, and behavior. Thus, as to distress in life, such as illness or disease, available coping strategies may be more important than the challenge itself. The same line of arguments applies to level of experienced health-related quality of life (HRQoL). Aim: The aim of this study was to investigate the relationship between distress, HRQoL, reported hearing loss, personality and coping in patients with HL. Method: 158 adult (aged 18-78 years) patients with HL, referred for hearing aid (HA) fitting at Haukeland University Hospital in western Norway, participated in the study. Both first-time users, as well as patients referred for HA renewals were included. First-time users had been pre-examined by an ENT-specialist. The questionnaires were answered before the actual HA fitting procedure. The pure-tone average (PTA; frequencies 0.5, 1, 2, and 4 kHz) was determined for each ear. The Eysenck personality inventory, neuroticism and lie scales, the Theoretically Originated Measure of the Cognitive Activation Theory of Stress (TOMCATS) measuring active coping, hopelessness and helplessness, as well as distress (General Health Questionnaire (GHQ) - 12 items) and the EORTC Quality of Life Questionnaire general part were answered. In addition, we used a revised and shortened version of the Abbreviated Profile of Hearing Aid Benefit (APHAB) as a measure of patient-reported hearing loss. Results: Significant correlations were determined between APHAB (weak), HRQoL scores (strong), distress scores (strong) on the one side and personality and choice of coping scores on the other side. As measured by stepwise regression analyses, the distress and HRQoL scores were scored secondary to the obtained personality and coping scores. The APHAB scores were as determined by regression analyses scored secondary to PTA (best ear), level of neuroticism and lie score. Conclusion: We found that reported employed coping style, distress/HRQoL and personality are closely connected to each other in this patient group. Patient-reported HL was associated to hearing level and personality. There is need for further investigations on these questions, and how these associations may influence the clinical context.Keywords: coping, distress, hearing loss, personality
Procedia PDF Downloads 1459593 Generation of Knowlege with Self-Learning Methods for Ophthalmic Data
Authors: Klaus Peter Scherer, Daniel Knöll, Constantin Rieder
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Problem and Purpose: Intelligent systems are available and helpful to support the human being decision process, especially when complex surgical eye interventions are necessary and must be performed. Normally, such a decision support system consists of a knowledge-based module, which is responsible for the real assistance power, given by an explanation and logical reasoning processes. The interview based acquisition and generation of the complex knowledge itself is very crucial, because there are different correlations between the complex parameters. So, in this project (semi)automated self-learning methods are researched and developed for an enhancement of the quality of such a decision support system. Methods: For ophthalmic data sets of real patients in a hospital, advanced data mining procedures seem to be very helpful. Especially subgroup analysis methods are developed, extended and used to analyze and find out the correlations and conditional dependencies between the structured patient data. After finding causal dependencies, a ranking must be performed for the generation of rule-based representations. For this, anonymous patient data are transformed into a special machine language format. The imported data are used as input for algorithms of conditioned probability methods to calculate the parameter distributions concerning a special given goal parameter. Results: In the field of knowledge discovery advanced methods and applications could be performed to produce operation and patient related correlations. So, new knowledge was generated by finding causal relations between the operational equipment, the medical instances and patient specific history by a dependency ranking process. After transformation in association rules logically based representations were available for the clinical experts to evaluate the new knowledge. The structured data sets take account of about 80 parameters as special characteristic features per patient. For different extended patient groups (100, 300, 500), as well one target value as well multi-target values were set for the subgroup analysis. So the newly generated hypotheses could be interpreted regarding the dependency or independency of patient number. Conclusions: The aim and the advantage of such a semi-automatically self-learning process are the extensions of the knowledge base by finding new parameter correlations. The discovered knowledge is transformed into association rules and serves as rule-based representation of the knowledge in the knowledge base. Even more, than one goal parameter of interest can be considered by the semi-automated learning process. With ranking procedures, the most strong premises and also conjunctive associated conditions can be found to conclude the interested goal parameter. So the knowledge, hidden in structured tables or lists can be extracted as rule-based representation. This is a real assistance power for the communication with the clinical experts.Keywords: an expert system, knowledge-based support, ophthalmic decision support, self-learning methods
Procedia PDF Downloads 2539592 Leveraging Digital Transformation Initiatives and Artificial Intelligence to Optimize Readiness and Simulate Mission Performance across the Fleet
Authors: Justin Woulfe
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Siloed logistics and supply chain management systems throughout the Department of Defense (DOD) has led to disparate approaches to modeling and simulation (M&S), a lack of understanding of how one system impacts the whole, and issues with “optimal” solutions that are good for one organization but have dramatic negative impacts on another. Many different systems have evolved to try to understand and account for uncertainty and try to reduce the consequences of the unknown. As the DoD undertakes expansive digital transformation initiatives, there is an opportunity to fuse and leverage traditionally disparate data into a centrally hosted source of truth. With a streamlined process incorporating machine learning (ML) and artificial intelligence (AI), advanced M&S will enable informed decisions guiding program success via optimized operational readiness and improved mission success. One of the current challenges is to leverage the terabytes of data generated by monitored systems to provide actionable information for all levels of users. The implementation of a cloud-based application analyzing data transactions, learning and predicting future states from current and past states in real-time, and communicating those anticipated states is an appropriate solution for the purposes of reduced latency and improved confidence in decisions. Decisions made from an ML and AI application combined with advanced optimization algorithms will improve the mission success and performance of systems, which will improve the overall cost and effectiveness of any program. The Systecon team constructs and employs model-based simulations, cutting across traditional silos of data, aggregating maintenance, and supply data, incorporating sensor information, and applying optimization and simulation methods to an as-maintained digital twin with the ability to aggregate results across a system’s lifecycle and across logical and operational groupings of systems. This coupling of data throughout the enterprise enables tactical, operational, and strategic decision support, detachable and deployable logistics services, and configuration-based automated distribution of digital technical and product data to enhance supply and logistics operations. As a complete solution, this approach significantly reduces program risk by allowing flexible configuration of data, data relationships, business process workflows, and early test and evaluation, especially budget trade-off analyses. A true capability to tie resources (dollars) to weapon system readiness in alignment with the real-world scenarios a warfighter may experience has been an objective yet to be realized to date. By developing and solidifying an organic capability to directly relate dollars to readiness and to inform the digital twin, the decision-maker is now empowered through valuable insight and traceability. This type of educated decision-making provides an advantage over the adversaries who struggle with maintaining system readiness at an affordable cost. The M&S capability developed allows program managers to independently evaluate system design and support decisions by quantifying their impact on operational availability and operations and support cost resulting in the ability to simultaneously optimize readiness and cost. This will allow the stakeholders to make data-driven decisions when trading cost and readiness throughout the life of the program. Finally, sponsors are available to validate product deliverables with efficiency and much higher accuracy than in previous years.Keywords: artificial intelligence, digital transformation, machine learning, predictive analytics
Procedia PDF Downloads 1609591 On-Site Management from Reactive to Proactive
Authors: Yu-Tzu Chen, Luh-Maan Chang
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Construction is an inherently risky industry. The projects have been dominated by reactive actions owing to non-routine in nature. The on-site activities are especially crucial for successful project control. In order to alter actions from reactive to proactive, this paper presents an on-site data collection system utilizing advanced technology RFID and GPS in assisting on-site management with near real time progress monitoring.Keywords: On-Site management, progress monitoring, RFID, GPS
Procedia PDF Downloads 5689590 Effect of Single Overload Ratio and Stress Ratio on Fatigue Crack Growth
Authors: M. Benachour, N. Benachour, M. Benguediab
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In this investigation, variation of cyclic loading effect on fatigue crack growth is studied. This study is performed on 2024 T351 and 7050-T74 aluminum alloys, used in aeronautical structures. The propagation model used in this study is NASGRO model. In constant amplitude loading (CA), the effect of stress ratio has been investigated. Fatigue life and fatigue crack growth rate were affected by this factor. Results showed an increasing in fatigue crack growth rates (FCGRs) with increasing stress ratio. Variable amplitude loading (VAL) can take many forms i.e with a single overload, overload band etc. The shape of these loads affects strongly the fracture life and FCGRs. The application of a single overload (ORL) decrease the FCGR and increase the delay crack length caused by the formation of a larger plastic zone compared to the plastic zone due without VAL. The fatigue behavior of the both material under single overload has been compared.Keywords: fatigue crack growth, overload ratio, stress ratio, generalized willenborg model, retardation, al-alloys
Procedia PDF Downloads 3639589 A Sociolinguistic Investigation of Code-Switching Practices of ESL Students Outside EFL Classrooms
Authors: Shehroz Mukhtar, Maqsood Ahmed, Abdullah Mukhtar, Choudhry Shahid, Waqar Javaid
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Code switching is a common phenomenon, generally observed in multilingual communities across the globe. A critical look at code-switching literature reveals that mostly code-switching has been studied in the classrooms in learning and teaching contexts, while code-switching outside the classroom in settings such as café, hostels and so on has been the least explored areas. The current research investigated the reasons for code-switching in the interactive practices of students and their perceptions regarding the same outside the classroom settings. This paper is the study of the common practice that prevails in the Universities of Sialkot that bilinguals mix two languages when they speak in different classroom situations. In Pakistani classrooms where Multilingual is in abundance, i.e. they can speak two or more two languages at the same time, code-switching or language combination is very common. The teachers of Sialkot switch from one language to another consciously or unconsciously while teaching English in the classrooms. This phenomenon has not been explored in Sialkot’s teaching context. In Sialkot, private educational institutes do not encourage code-switching, whereas public or government institutes use it frequently. The crux of this research is to investigate and identify the importance of code-switching by taking its users into consideration. The survey research method and survey questionnaire will be used to get exact data from teachers and students. We will try to highlight the functions and importance of code switching in foreign language classrooms of Sialkot and will explore why this trend is emerging in Sialkot.Keywords: code switching, foreign language classrooms, bilingual context, use of L1, importance of L2.
Procedia PDF Downloads 669588 Subtitling in the Classroom: Combining Language Mediation, ICT and Audiovisual Material
Authors: Rossella Resi
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This paper describes a project carried out in an Italian school with English learning pupils combining three didactic tools which are attested to be relevant for the success of young learner’s language curriculum: the use of technology, the intralingual and interlingual mediation (according to CEFR) and the cultural dimension. Aim of this project was to test a technological hands-on translation activity like subtitling in a formal teaching context and to exploit its potential as motivational tool for developing listening and writing, translation and cross-cultural skills among language learners. The activities proposed involved the use of professional subtitling software called Aegisub and culture-specific films. The workshop was optional so motivation was entirely based on the pleasure of engaging in the use of a realistic subtitling program and on the challenge of meeting the constraints that a real life/work situation might involve. Twelve pupils in the age between 16 and 18 have attended the afternoon workshop. The workshop was organized in three parts: (i) An introduction where the learners were opened up to the concept and constraints of subtitling and provided with few basic rules on spotting and segmentation. During this session learners had also the time to familiarize with the main software features. (ii) The second part involved three subtitling activities in plenum or in groups. In the first activity the learners experienced the technical dimensions of subtitling. They were provided with a short video segment together with its transcription to be segmented and time-spotted. The second activity involved also oral comprehension. Learners had to understand and transcribe a video segment before subtitling it. The third activity embedded a translation activity of a provided transcription including segmentation and spotting of subtitles. (iii) The workshop ended with a small final project. At this point learners were able to master a short subtitling assignment (transcription, translation, segmenting and spotting) on their own with a similar video interview. The results of these assignments were above expectations since the learners were highly motivated by the authentic and original nature of the assignment. The subtitled videos were evaluated and watched in the regular classroom together with other students who did not take part to the workshop.Keywords: ICT, L2, language learning, language mediation, subtitling
Procedia PDF Downloads 4169587 Biological Significance of Long Intergenic Noncoding RNA LINC00273 in Lung Cancer Cell Metastasis
Authors: Ipsita Biswas, Arnab Sarkar, Ashikur Rahaman, Gopeswar Mukherjee, Subhrangsu Chatterjee, Shamee Bhattacharjee, Deba Prasad Mandal
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One of the major reasons for the high mortality rate of lung cancer is the substantial delays in disease detection at late metastatic stages. It is of utmost importance to understand the detailed molecular signaling and detect the molecular markers that can be used for the early diagnosis of cancer. Several studies explored the emerging roles of long noncoding RNAs (lncRNAs) in various cancers as well as lung cancer. A long non-coding RNA LINC00273 was recently discovered to promote cancer cell migration and invasion, and its positive correlation with the pathological stages of metastasis may prove it to be a potential target for inhibiting cancer cell metastasis. Comparing real-time expression of LINC00273 in various human clinical cancer tissue samples with normal tissue samples revealed significantly higher expression in cancer tissues. This long intergenic noncoding RNA was found to be highly expressed in human liver tumor-initiating cells, human gastric adenocarcinoma AGS cell line, as well as human non-small cell lung cancer A549 cell line. SiRNA and shRNA-induced knockdown of LINC00273 in both in vitro and in vivo nude mice significantly subsided AGS and A549 cancer cell migration and invasion. LINC00273 knockdown also reduced TGF-β induced SNAIL, SLUG, VIMENTIN, ZEB1 expression, and metastasis in A549 cells. Plenty of reports have suggested the role of microRNAs of the miR200 family in reversing epithelial to mesenchymal transition (EMT) by inhibiting ZEB transcription factors. In this study, hsa-miR-200a-3p was predicted via IntaRNA-Freiburg RNA tools to be a potential target of LINC00273 with a negative free binding energy of −8.793 kcal/mol, and this interaction was verified as a confirmed target of LINC00273 by RNA pulldown, real-time PCR and luciferase assay. Mechanistically, LINC00273 accelerated TGF-β induced EMT by sponging hsa-miR-200a-3p which in turn liberated ZEB1 and promoted prometastatic functions in A549 cells in vitro as verified by real-time PCR and western blotting. The similar expression patterns of these EMT regulatory pathway molecules, viz. LINC00273, hsa-miR-200a-3p, ZEB1 and TGF-β, were also detected in various clinical samples like breast cancer tissues, oral cancer tissues, lung cancer tissues, etc. Overall, this LINC00273 mediated EMT regulatory signaling can serve as a potential therapeutic target for the prevention of lung cancer metastasis.Keywords: epithelial to mesenchymal transition, long noncoding RNA, microRNA, non-small-cell lung carcinoma
Procedia PDF Downloads 1569586 Carbon Footprint of Road Project for Sustainable Development: Lessons Learnt from Traffic Management of a Developing Urban Centre
Authors: Sajjad Shukur Ullah, Syed Shujaa Safdar Gardezi
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Road infrastructure plays a vital role in the economic activities of any economy. Besides derived benefits from these facilities, the utilization of extensive energy resources, fuels, and materials results in a negative impact on the environment in terms of carbon footprint; carbon footprint is the overall amount of greenhouse gas (GHG) generated from any action. However, this aspect of environmental impact from road structure is not seriously considered during such developments, thus undermining a critical factor of sustainable development, which usually remains unaddressed, especially in developing countries. The current work investigates the carbon footprint impact of a small road project (0.8 km, dual carriageway) initiated for traffic management in an urban centre. Life cycle assessment (LCA) with boundary conditions of cradle to the site has been adopted. The only construction phase of the life cycle has been assessed at this stage. An impact of 10 ktons-CO2 (6260 ton-CO2/km) has been assessed. The rigid pavement dominated the contributions as compared to a flexible component. Among the structural elements, the underpass works shared the major portion. Among the materials, the concrete and steel utilized for various structural elements resulted in more than 90% of the impact. The earth-moving equipment was dominant in operational carbon. The results have highlighted that road infrastructure projects pose serious threats to the environment during their construction and which need to be considered during the approval stages. This work provides a guideline for supporting sustainable development that could only be ensured when such endeavours are properly assessed by industry professionals and decide various alternative environmental conscious solutions for the future.Keywords: construction waste management, kiloton, life cycle assessment, rigid pavement
Procedia PDF Downloads 1009585 Effects of Injectable Thermosensitive Hydrogel Containing Chitosan as a Barrier for Prevention of Post-operative Peritoneal Adhesion in Rats
Authors: Sara Javanmardi, Sepehr Aziziz, Baharak Divband, Masoumeh Firouzamandi
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Post-operative adhesions are the most common cause of intestinal obstruction, female infertility and chronic abdominal pain. We developed a novel approach for preventing post-operative peritoneal adhesions using a biodegradable and thermosensitive curcumin hydrogel in rats. Thirteen male Sprague-Dawley rats were assigned randomly into five groups of six animals each: In SHAM group, the cecum was exteriorized, gently manipulated and sent back into the abdomen. In CONTROL group, the surgical abrasion was performed with no further treatment. In Hydrogel group, surgical abrasion was performed with local application of blank hydrogel (1 mL). In Curcumin group, surgical abrasion was performed with local application of curcumin (1 mL). In CUR/HGEL group, surgical abrasion was performed with local application of curcumin hydrogel (1 mL). On day 10, adhesions were assessed using a standardized scale (Evans model), and samples were collected for the Real-time PCR. Real-time PCR was performed to determine mRNA levels of VCAM-1, ICAM-1 and GAPDH. The macroscopic adhesion intensity showed statistically significant differences between the CUR/HGEL and other groups (P=0.0005). The findings of the present study revealed there were statistically significant differences between the groups regarding adhesion band length and numbers (P<0.0001). The protein and mRNA expression of VCAM-1 and ICAM-1 in secal tissues were significantly down regulated due to curcumin-hydrogel application in CUR/HGEL compared to other groups (p<0.05). The thermosensitive hydrogel could reduce the severity and even prevent formation of intra-abdominal adhesion. Curcumin hydrogel could serve as a potential barrier agent to prevent post-operative peritoneal adhesion in rats.Keywords: peritoneal adhesion, hydrogel, curcumijn, ICAM-1, VCAM-1
Procedia PDF Downloads 899584 Seismic Vulnerability Mitigation of Non-Engineered Buildings
Authors: Muhammad Tariq A. Chaudhary
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The tremendous loss of life that resulted in the aftermath of recent earthquakes in developing countries is mostly due to the collapse of non-engineered and semi-engineered building structures. Such structures are used as houses, schools, primary healthcare centres and government offices. These building are classified structurally into two categories viz. non-engineered and semi-engineered. Non-engineered structures include: adobe, Unreinforced Masonry (URM) and wood buildings. Semi-engineered buildings are mostly low-rise (up to 3 story) light concrete frame structures or masonry bearing walls with reinforced concrete slab. This paper presents an overview of the typical damage observed in non-engineered structures and their most likely causes in the past earthquakes with specific emphasis on the performance of such structures in the 2005 Kashmir earthquake. It is demonstrated that seismic performance of these structures can be improved from life-safety viewpoint by adopting simple low-cost modifications to the existing construction practices. Incorporation of some of these practices in the reconstruction efforts after the 2005 Kashmir earthquake are examined in the last section for mitigating seismic risk hazard.Keywords: Kashmir earthquake, non-engineered buildings, seismic hazard, structural details, structural strengthening
Procedia PDF Downloads 2869583 Coping Strategies Used by Persons with Spinal Cord Injury: A Rehabilitation Hospital Based Qualitative Study
Authors: P. W. G. D. P. Samarasekara, S. M. K. S. Seneviratne, D. Munidasa, S. S. Williams
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Sustaining a spinal cord injury (SCI) causes severe disruption of all aspects of a person’s life, resulting in the difficult process of coping with the distressing effects of paralysis affecting their ability to lead a meaningful life. These persons are hospitalized in the acute stage of injury and subsequently for rehabilitation and the treatment of complications. The purpose of this study was to explore coping strategies used by persons with SCI during their rehabilitation period. A qualitative study was conducted among persons with SCI, undergoing rehabilitation at the Rheumatology and Rehabilitation Hospitals, Ragama and Digana Sri Lanka. Twelve participants were selected purposively to represent both males and females, with cervical, thoracic or lumbar levels of injuries due to traumatic and non-traumatic causes as well as from different socioeconomic backgrounds. Informed consent was taken from the participants. In-depth interviews were conducted using an interview guide to collect data. Probes were used to get more information and to encourage participants. Interviews were audio taped and transcribed verbatim. Qualitative content analysis was conducted. Ethical approval for this study was obtained from the Ethics Review Committee, Faculty of Medicine, University of Kelaniya. Five themes were identified in the content analysis: social support, religious beliefs, determination, acceptance and making comparisons. Participants indicated that the support from their family members had been an essential factor in coping, after sustaining an SCI and they expressed the importance of emotional support from family members during their rehabilitation. Many participants had a strong belief towards the God, who had a personal interest in their lives, played an important role in their ability to cope with the injury. They believed that what happens to them in this life results from their actions in previous lives. They expressed that determination was essential as a factor that helps them cope with their injury. They indicated their focus on the positive aspects of the life and accepted the disability. They made comparisons to other persons who were worse off than them to help lift them out of unpleasant experience. Even some of the most severely injured and disabled participants presented evidence of using this coping strategy. Identification of coping strategies used by persons with SCI will help nurses and other health-care professionals in reinforcing the most effective coping strategies among persons with SCI. The findings recommend that engagement coping positively influences psychosocial adaptation.Keywords: content analysis, coping strategies, rehabilitation, spinal cord injury
Procedia PDF Downloads 1859582 A Demonstration of How to Employ and Interpret Binary IRT Models Using the New IRT Procedure in SAS 9.4
Authors: Ryan A. Black, Stacey A. McCaffrey
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Over the past few decades, great strides have been made towards improving the science in the measurement of psychological constructs. Item Response Theory (IRT) has been the foundation upon which statistical models have been derived to increase both precision and accuracy in psychological measurement. These models are now being used widely to develop and refine tests intended to measure an individual's level of academic achievement, aptitude, and intelligence. Recently, the field of clinical psychology has adopted IRT models to measure psychopathological phenomena such as depression, anxiety, and addiction. Because advances in IRT measurement models are being made so rapidly across various fields, it has become quite challenging for psychologists and other behavioral scientists to keep abreast of the most recent developments, much less learn how to employ and decide which models are the most appropriate to use in their line of work. In the same vein, IRT measurement models vary greatly in complexity in several interrelated ways including but not limited to the number of item-specific parameters estimated in a given model, the function which links the expected response and the predictor, response option formats, as well as dimensionality. As a result, inferior methods (a.k.a. Classical Test Theory methods) continue to be employed in efforts to measure psychological constructs, despite evidence showing that IRT methods yield more precise and accurate measurement. To increase the use of IRT methods, this study endeavors to provide a comprehensive overview of binary IRT models; that is, measurement models employed on test data consisting of binary response options (e.g., correct/incorrect, true/false, agree/disagree). Specifically, this study will cover the most basic binary IRT model, known as the 1-parameter logistic (1-PL) model dating back to over 50 years ago, up until the most recent complex, 4-parameter logistic (4-PL) model. Binary IRT models will be defined mathematically and the interpretation of each parameter will be provided. Next, all four binary IRT models will be employed on two sets of data: 1. Simulated data of N=500,000 subjects who responded to four dichotomous items and 2. A pilot analysis of real-world data collected from a sample of approximately 770 subjects who responded to four self-report dichotomous items pertaining to emotional consequences to alcohol use. Real-world data were based on responses collected on items administered to subjects as part of a scale-development study (NIDA Grant No. R44 DA023322). IRT analyses conducted on both the simulated data and analyses of real-world pilot will provide a clear demonstration of how to construct, evaluate, and compare binary IRT measurement models. All analyses will be performed using the new IRT procedure in SAS 9.4. SAS code to generate simulated data and analyses will be available upon request to allow for replication of results.Keywords: instrument development, item response theory, latent trait theory, psychometrics
Procedia PDF Downloads 3579581 Enhancing Scalability in Ethereum Network Analysis: Methods and Techniques
Authors: Stefan K. Behfar
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The rapid growth of the Ethereum network has brought forth the urgent need for scalable analysis methods to handle the increasing volume of blockchain data. In this research, we propose efficient methodologies for making Ethereum network analysis scalable. Our approach leverages a combination of graph-based data representation, probabilistic sampling, and parallel processing techniques to achieve unprecedented scalability while preserving critical network insights. Data Representation: We develop a graph-based data representation that captures the underlying structure of the Ethereum network. Each block transaction is represented as a node in the graph, while the edges signify temporal relationships. This representation ensures efficient querying and traversal of the blockchain data. Probabilistic Sampling: To cope with the vastness of the Ethereum blockchain, we introduce a probabilistic sampling technique. This method strategically selects a representative subset of transactions and blocks, allowing for concise yet statistically significant analysis. The sampling approach maintains the integrity of the network properties while significantly reducing the computational burden. Graph Convolutional Networks (GCNs): We incorporate GCNs to process the graph-based data representation efficiently. The GCN architecture enables the extraction of complex spatial and temporal patterns from the sampled data. This combination of graph representation and GCNs facilitates parallel processing and scalable analysis. Distributed Computing: To further enhance scalability, we adopt distributed computing frameworks such as Apache Hadoop and Apache Spark. By distributing computation across multiple nodes, we achieve a significant reduction in processing time and enhanced memory utilization. Our methodology harnesses the power of parallelism, making it well-suited for large-scale Ethereum network analysis. Evaluation and Results: We extensively evaluate our methodology on real-world Ethereum datasets covering diverse time periods and transaction volumes. The results demonstrate its superior scalability, outperforming traditional analysis methods. Our approach successfully handles the ever-growing Ethereum data, empowering researchers and developers with actionable insights from the blockchain. Case Studies: We apply our methodology to real-world Ethereum use cases, including detecting transaction patterns, analyzing smart contract interactions, and predicting network congestion. The results showcase the accuracy and efficiency of our approach, emphasizing its practical applicability in real-world scenarios. Security and Robustness: To ensure the reliability of our methodology, we conduct thorough security and robustness evaluations. Our approach demonstrates high resilience against adversarial attacks and perturbations, reaffirming its suitability for security-critical blockchain applications. Conclusion: By integrating graph-based data representation, GCNs, probabilistic sampling, and distributed computing, we achieve network scalability without compromising analytical precision. This approach addresses the pressing challenges posed by the expanding Ethereum network, opening new avenues for research and enabling real-time insights into decentralized ecosystems. Our work contributes to the development of scalable blockchain analytics, laying the foundation for sustainable growth and advancement in the domain of blockchain research and application.Keywords: Ethereum, scalable network, GCN, probabilistic sampling, distributed computing
Procedia PDF Downloads 769580 The Decline of Verb-Second in the History of English: Combining Historical and Theoretical Explanations for Change
Authors: Sophie Whittle
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Prior to present day, English syntax historically exhibited an inconsistent verb-second (V2) rule, which saw the verb move to the second position in the sentence following the fronting of a type of phrase. There was a high amount of variation throughout the history of English with regard to the ordering of subject and verb, and many explanations attempting to account for this variation have been documented in previous literature. However, these attempts have been contradictory, with many accounts positing the effect of previous syntactic changes as the main motivations behind the decline of V2. For instance, morphosyntactic changes, such as the loss of clitics and the loss of empty expletives, have been loosely connected to changes in frequency for the loss of V2. The questions surrounding the development of non-V2 in English have, therefore, yet to be answered. The current paper aims to bring together a number of explanations from different linguistic fields to determine the factors driving the changes in English V2. Using historical corpus-based methods, the study analyses both quantitatively and qualitatively the changes in frequency for the history of V2 in the Old, Middle, and Modern English periods to account for the variation in a range of sentential environments. These methods delve into the study of information structure, prosody and language contact to explain variation within different contexts. The analysis concludes that these factors, in addition to changes within the syntax, are responsible for the position of verb movement. The loss of V2 serves as an exemplar study within the field of historical linguistics, which combines a number of factors in explaining language change in general.Keywords: corpora, English, language change, mixed-methods, syntax, verb-second
Procedia PDF Downloads 1359579 Embracing Our Scars: Self-Harm 101
Authors: Bree Wiles
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Self-harm is still a topic that is not talked about enough, especially with the growing concern for the safety of LGBTQIA+ youth. LGBTQIA+ youth are coming out at earlier ages, thus bringing to attention the added risks for this population. Many LGBTQIA+ youth end up engaging in some form of self-destructive behavior from dealing with the stigma and negative socialization around them. Within the LGBTQIA+ youth population, self-harm alongside depression and suicide is especially common. This disparity shows the importance of providing LGBTQIA+ youth with resources that affirm their identities. As professionals and parents, it is important to understand the types of self-harm, the average age range when it can occur, causes, populations, risk factors, and self-harm in connection with mental health and suicide. It is imperative to provide protective factors for LGBTQIA+ youth in helping to replace self-harming behaviors with positive coping strategies. Helping LGBTQIA+ youth in different contexts, including from a professional, parent, and educator perspective, allows unique ways in which each can assist an LGBTQIA+ youth who is self-harming. The stigma, shame, and many misconceptions about self-harming behaviors are discussed in depth including from the lived experience of this author and professional experiences working with queer youth. Most importantly, it is imperative to know how to approach LGBTQIA+ youth who are self-harming, including how to speak in a compassionate and empathy-based framework. Clear interventions and therapeutic techniques based on evidence-based practices on alternatives to self-harm, lived experience, and previous practices with queer youth who are self-harming are provided and discussed.Keywords: LGBTQ+, mental health, self-harm, depression
Procedia PDF Downloads 529578 Topology and Shape Optimization of Macpherson Control Arm under Fatigue Loading
Authors: Abolfazl Hosseinpour, Javad Marzbanrad
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In this research, the topology and shape optimization of a Macpherson control arm has been accomplished to achieve lighter weight. Present automotive market demands low cost and light weight component to meet the need of fuel efficient and cost effective vehicle. This in turn gives the rise to more effective use of materials for automotive parts which can reduce the mass of vehicle. Since automotive components are under dynamic loads which cause fatigue damage, considering fatigue criteria seems to be essential in designing automotive components. At first, in order to create severe loading condition for control arm, some rough roads are generated through power spectral density. Then, the most critical loading conditions are obtained through multibody dynamics analysis of a full vehicle model. Then, the topology optimization is performed based on fatigue life criterion using HyperMesh software, which resulted to 50 percent mass reduction. In the next step a CAD model is created using CATIA software and shape optimization is performed to achieve accurate dimensions with less mass.Keywords: topology optimization, shape optimization, fatigue life, MacPherson control arm
Procedia PDF Downloads 3169577 Consensual A-Monogamous Relationships: Challenges and Ways of Coping
Authors: Tal Braverman Uriel, Tal Litvak Hirsch
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Background and Objectives: Little or only partial emphasis has been placed on exploring the complexity of consensual non-monogamous relationships. The term "polyamory" refers to consensual non-monogamy, and it is defined as having emotional and/or sexual relations simultaneously with two or more people, the consent and knowledge of all the partners concerned. Managing multiple romantic relationships with different people evokes more emotions, leads to more emotional conflicts arising from different interests, and demands practical strategies. An individual's transition from a monogamous lifestyle to a consensual non-monogamous lifestyle yields new challenges, accompanied by stress, uncertainty, and question marks, as do other life-changing events, such as divorce or transition to parenthood. The study examines both the process of transition and adaptation to a consensually non-monogamous relationship, as well as the coping mechanism involved in the daily conduct of this lifestyle. The research focuses on understanding the consequences, challenges, and coping methods from a personal, marital, and familial point of view and focuses on 40 middle-aged individuals (20 men and 20 women ages 40-60). The research sheds light on a way of life that has not been previously studied in Israel and is still considered unacceptable. Theories of crisis (e.g., as Folkman and Lazarus) were applied, and as a result, a deeper understanding of the subject was reached, all while focusing on multiple aspects of dealing with stress. The basic research question examines the consequences of entering a polyamorous life from a personal point of view as an individual, partner, and parent and the ways of coping with these consequences. Method: The research is conducted with a narrative qualitative approach in the interpretive paradigm, including semi-structured in-depth interviews. The method of analysis is thematic. Results: The findings indicate that in most cases, an individual's motivation to open the relationship is mainly a longing for better sexuality and for an added layer of excitement to their lives. Most of the interviewees were assisted by their spouses in the process, as well as by social networks and podcasts on the subject. Some of them therapeutic professionals from the field are helpful. It also clearly emerged that among those who experienced acute emotional crises with the primary partner or painful separations from secondary partners, all believed polyamory to be the adequate way of life for them. Finally, a key resource for managing tension and stress is the ability to share and communicate with the primary partner. Conclusions: The study points to the challenges and benefits of a non-monogamous lifestyle as well as the use of coping mechanisms and resources that are consistent with the existing theory and research in the field in the context of life changes. The study indicates the need to expand the research canvas in the future in the context of parenting and the consequences for children.Keywords: a-monogamy, consent, family, stress, tension
Procedia PDF Downloads 769576 Active Control Effects on Dynamic Response of Elevated Water Storage Tanks
Authors: Ali Etemadi, Claudia Fernanda Yasar
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Elevated water storage tank structures (EWSTs) are high elevated-ponderous structural systems and very vulnerable to seismic vibrations. In past earthquake events, many of these structures exhibit poor performance and experienced severe damage. The dynamic analysis of the EWSTs under earthquake loads is, therefore, of significant importance for the design of the structure and a key issue for the development of modern methods, such as active control design. In this study, a reduced model of the EWSTs is explained, which is based on a tuned mass damper model (TMD). Vibration analysis of a structure under seismic excitation is presented and then used to propose an active vibration controller. MATLAB/Simulink is employed for dynamic analysis of the system and control of the seismic response. A single degree of freedom (SDOF) and two degree of freedom (2DOF) models of ELSTs are going to be used to study the concept of active vibration control. Lab-scale experimental models similar to pendulum are applied to suppress vibrations in ELST under seismic excitation. One of the most important phenomena in liquid storage tanks is the oscillation of fluid due to the movements of the tank body because of its base motions during an earthquake. Simulation results illustrate that the EWSTs vibration can be reduced by means of an input shaping technique that takes into account the dominant mode shape of the structure. Simulations with which to guide many of our designs are presented in detail. A simple and effective real-time control for seismic vibration damping can be, therefore, design and built-in practice.Keywords: elevated water storage tank, tuned mass damper model, real time control, shaping control, seismic vibration control, the laplace transform
Procedia PDF Downloads 1529575 Pragmatic Competence of Jordanian EFL Learners
Authors: Dina Mahmoud Hammouri
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The study investigates the Jordanian EFL learners’ pragmatic competence through their production of the speech acts of responding to requests, making suggestions, making threats and expressing farewells. The sample of the study consists of 130 Jordanian EFL learners and native speakers. 2600 responses were collected through a Discourse Completion Test (DCT). The findings of the study revealed that the tested students showed similarities and differences in performing the strategies of four speech acts. Differences in the students’ performances led to pragmatic failure instances. The pragmatic failure committed by students refers to a lack of linguistic competence (i.e., pragmalinguistic failure), sociocultural differences and pragmatic transfer (i.e., sociopragmatic failure). EFL learners employed many mechanisms to maintain their communicative competence; the analysis of the test on speech acts showed learners’ tendency towards using particular strategies, resorting to modify strategies and relating them to their grammatical competence, prefabrication, performing long forms, buffing and transfer. The results were also suggestive of the learners’ lack of pragmalinguistic and sociopragmatic knowledge. The implications of this study are for language teachers to teach interlanguage pragmatics explicitly in EFL contexts to draw learners’ attention to both pragmalinguistic and sociopragmatic features, pay more attention to these areas and allocate more time and practice to solve learners’ problems in these areas. The implication of this study is also for pedagogical material designers to provide sufficient and well-organized pragmatic input.Keywords: pragmatic failure, Jordanian EFL learner, sociopragmatic competence, pragmalinguistic competence
Procedia PDF Downloads 809574 A Proposed Mechanism for Skewing Symmetric Distributions
Authors: M. T. Alodat
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In this paper, we propose a mechanism for skewing any symmetric distribution. The new distribution is called the deflation-inflation distribution (DID). We discuss some statistical properties of the DID such moments, stochastic representation, log-concavity. Also we fit the distribution to real data and we compare it to normal distribution and Azzlaini's skew normal distribution. Numerical results show that the DID fits the the tree ring data better than the other two distributions.Keywords: normal distribution, moments, Fisher information, symmetric distributions
Procedia PDF Downloads 6599573 Anthropological Basis of Arguments in Plato’s Protagoras
Authors: Zahra Nouri Sangedehy
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There are two anthropologies considered in Protagoras. The first of them (Protagoras) considers the appearance of man, like all other beings, as the result of a natural evolution without a predetermined plan and aim. Not only the human's corporeal existence is the result of evolution and natural choices, but also his moral and social life can be explained in the light of this factor. In this anthropology, the moral and political laws derive from the contract and the people's majority agreement of society to survive. Society and socio-political institutions are the reason for the education and training (paidia) of virtues in general. The second anthropology is Socrates's, which is not clearly projected and is hidden behind his arguments. In this way, man's moral and social life is intrinsic. Man is intrinsically a moral and social being. Socrates intends to criticize the theory of the contractual nature of ethics by demonstrating the unity of virtues on the one hand and the identity of virtue and knowledge, and the problem of the teaching of virtues based on intrinsic and a priori knowledge of human beings, on the other hand, albeit with a new kind of education and training, which will replace the Sophists' education. Therefore, ethics will have undoubted foundations, and human beings will be defined again.Keywords: Protagoras, techne, arête, paidia
Procedia PDF Downloads 939572 Healthy Lifestyle and Quality of Life in Carintia Region, Slovenia
Authors: Pirjo Kaakinen, Helvi Kyngäs, Danica Železnik
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People live longer than earlier and healthy lifestyle is one of the important issue to prevent functional inability and chronic disease. Aim of this study was describe the lifestyle changes of Carintia region’s people. The study was cross-sectional study. Data were collected by questionnaire in two period, first May 2013 (N=63) and on March 2014 (N=77) at the University of College of ‘Health Sciences Slovenj Gradec’. The study was part of project ‘Choose a healthy lifestyle - an investment for the future’. The questionnaire included self-estimated questions about physical activity, nutrition, grocery habit, smoking habit and alcohol use. Participants were measured clinical parameters such as blood pressure, blood glucose, BMI. Most of participants were women (61%) and they were over 60 years old (64%). Participants have a high BMI (75%) and elevated blood pressure (64%). However, almost all participants (89%) had normal blood glucose level. Slightly more than half of participants (54%) have normal cholesterol level. Participants (83%) eat breakfast in the morning and most of them have three or four daily meals. Fruit and vegetable consumption decrease during this study. Half of participants (51%) drank a litre of water per day and popular beverage was coffee or tea. To drink carbonate beverages was not so popular over 60 year’s old participants than younger one. There was less smokers in 2014 than 2013. Intensity of daily physical activity increased during healthy lifestyle project. The most popular form of physical activity was hiking. This study showed that the project can be effective in the Carintia region’s people lifestyle changes even it was short time. People did changes in their daily life and there were a positive influence physical activity, meal frequency, fruit, vegetable and alcohol consumption. In the future is needed the follow up study to get out longitudinal lifestyle changes.Keywords: adults, healthy lifestyle, health education, quality of life
Procedia PDF Downloads 2679571 Unpacking the Spatial Outcomes of Public Transportation in a Developing Country Context: The Case of Johannesburg
Authors: Adedayo B. Adegbaju, Carel B. Schoeman, Ilse M. Schoeman
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The unique urban contexts that emanated from the apartheid history of South Africa informed the transport landscape of the City of Johannesburg. Apartheid‘s divisive spatial planning and land use management policies promoted sprawling and separated workers from job opportunities. This was further exacerbated by poor funding of public transport and road designs that encouraged the use of private cars. However, the democratization of the country in 1994 and the hosting of the 2010 FIFA World Cup provided a new impetus to the city’s public transport-oriented urban planning inputs. At the same time, the state’s new approach to policy formulations that entails the provision of public transport as one of the tools to end years of marginalization and inequalities soon began to largely reflect in planning decisions of other spheres of government. The Rea Vaya BRT and the Gautrain were respectively implemented by the municipal and provincial governments to demonstrate strong political will and commitment to the new policy direction. While the Gautrain was implemented to facilitate elite movement within Gauteng and to crowd investments and economic growths around station nodes, the BRT was provided for previously marginalized public transport users to provide a sustainable alternative to the dominant minibus taxi. The aim of this research is to evaluate the spatial impacts of the Gautrain and Rea Vaya BRT on the City of Johannesburg and to inform future outcomes by determining the existing potentials. By using the case study approach with a focus on the BRT and fast rail in a metropolitan context, the triangulation research method, which combines various data collection methods, was used to determine the research outcomes. The use of interviews, questionnaires, field observation, and databases such as REX, Quantec, StatsSA, GCRO observatory, national and provincial household travel surveys, and the quality of life surveys provided the basis for data collection. The research concludes that the Gautrain has demonstrated that viable alternatives to the private car can be provided, with its satisfactory feedbacks from users; while some of its station nodes (Sandton, Rosebank) have shown promises of transit-oriented development, one of the project‘s key objectives. The other stations have been unable to stimulate growth due to reasons like non-implementation of their urban design frameworks and lack of public sector investment required to attract private investors. The Rea Vaya BRT continues to be expanded in spite of both its inability to induce modal change and its low ridership figures. The research identifies factors like the low peak to base ratio, pricing, and the city‘s disjointed urban fabric as some of the reasons for its below-average performance. By drawing from the highlights and limitations, the study recommends that public transport provision should be institutionally integrated across and within spheres of government. Similarly, harmonization of the funding structure, better understanding of users’ needs, and travel patterns, underlined with continuity of policy direction and objectives, will equally promote optimal outcomes.Keywords: bus rapid transit, Gautrain, Rea Vaya, sustainable transport, spatial and transport planning, transit oriented development
Procedia PDF Downloads 1149570 Engaging Students in Learning through Visual Demonstration Models in Engineering Education
Authors: Afsha Shaikh, Mohammed Azizur Rahman, Ibrahim Hassan, Mayur Pal
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Student engagement in learning is instantly affected by the sources of learning methods available for them, such as videos showing the applications of the concept or showing a practical demonstration. Specific to the engineering discipline, there exist enormous challenging concepts that can be simplified when they are connected to real-world scenarios. For this study, the concept of heat exchangers was used as it is a part of multidisciplinary engineering fields. To make the learning experience enjoyable and impactful, 3-D printed heat exchanger models were created for students to use while working on in-class activities and assignments. Students were encouraged to use the 3-D printed heat exchanger models to enhance their understanding of theoretical concepts associated with its applications. To assess the effectiveness of the method, feedback was received by students pursuing undergraduate engineering via an anonymous electronic survey. To make the feedback more realistic, unbiased, and genuine, students spent nearly two to three weeks using the models in their in-class assignments. The impact of these tools on their learning was assessed through their performance in their ungraded assignments as well as their interactive discussions with peers. ‘Having to apply the theory learned in class whilst discussing with peers on a class assignment creates a relaxed and stress-free learning environment in classrooms’; this feedback was received by more than half the students who took the survey and found 3-D models of heat exchanger very easy to use. Amongst many ways to enhance learning and make students more engaged through interactive models, this study sheds light on the importance of physical tools that help create a lasting mental representation in the minds of students. Moreover, in this technologically enhanced era, the concept of augmented reality was considered in this research. E-drawings application was recommended to enhance the vision of engineering students so they can see multiple views of the detailed 3-D models and cut through its different sides and angles to visualize it properly. E-drawings could be the next tool to implement in classrooms to enhance students’ understanding of engineering concepts.Keywords: student engagement, life-long-learning, visual demonstration, 3-D printed models, engineering education
Procedia PDF Downloads 1159569 Teachers as Agents of Change in Diverse Classrooms: An Overview of the Literature
Authors: Anna Sanczyk
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Diverse students may experience different forms of discrimination. Some of the oppression students experience in schools are racism, sexism, classism, or homophobia that may affect their achievement, and teachers need to make sure they create inclusive, equitable classroom environments. The broader literature on social change in education shows that teachers who challenge oppression and want to promote equitable and transformative education face institutional, social, and political constraints. This paper discusses research on teachers’ work to create socially just and culturally inclusive classrooms and schools. The practical contribution of this literature review is that it provides a comprehensive compilation of the studies presenting teachers’ roles and efforts in affecting social change. The examination of the research on social change in education points to the urgency of teachers addressing the needs of marginalized students and resisting systemic oppression in schools. The implications of this literature review relate to the concerns that schools should provide greater advocacy for marginalized students in diverse learning contexts, and teacher education programs should prepare teachers to be active advocates for diverse students. The literature review has the potential to inform educators to enhance educational equity and improve the learning environment. This literature review illustrates teachers as agents of change in diverse classrooms and contributes to understanding various ways of taking action towards fostering more equitable and transformative education in today’s schools.Keywords: agents of change, diversity, opression, social change
Procedia PDF Downloads 1409568 Development of Residual Power Series Methods for Efficient Solutions of Stiff Differential Equations
Authors: Gebreegziabher Hailu
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This paper presents the development of residual power series methods aimed at efficiently solving stiff differential equations, which pose significant challenges in numerical analysis due to their rapid changes in solution behavior. The RPSM is a numerical approach that generates polynomial-based approximate solutions without the need for linearization, discretization, or perturbation techniques, making it straightforward to implement and less prone to computational errors. We introduce an approach that utilizes power series expansions combined with residual minimization techniques to enhance convergence and stability. By analyzing the theoretical foundations of stiffness, we delve into the formulation of the residual power series method, detailing how it effectively captures the dynamics of stiff systems while maintaining computational efficiency. Numerical experiments demonstrate the method's superiority in terms of accuracy and computational cost when compared to traditional methods like implicit Runge-Kutta or multistep techniques. We also explore adaptive strategies within our framework to automatically adjust parameters based on the stiffness characteristics of the problem at hand. Ultimately, our findings contribute to the broader toolkit for tackling stiff differential equations, offering a robust alternative that promises to streamline computational workflows in various applied mathematics and engineering contexts.Keywords: residual power series methods, stiff differential equoations, numerical approach, Runge Kutta methods
Procedia PDF Downloads 239567 The Structure and Function Investigation and Analysis of the Automatic Spin Regulator (ASR) in the Powertrain System of Construction and Mining Machines with the Focus on Dump Trucks
Authors: Amir Mirzaei
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The powertrain system is one of the most basic and essential components in a machine. The occurrence of motion is practically impossible without the presence of this system. When power is generated by the engine, it is transmitted by the powertrain system to the wheels, which are the last parts of the system. Powertrain system has different components according to the type of use and design. When the force generated by the engine reaches to the wheels, the amount of frictional force between the tire and the ground determines the amount of traction and non-slip or the amount of slip. At various levels, such as icy, muddy, and snow-covered ground, the amount of friction coefficient between the tire and the ground decreases dramatically and considerably, which in turn increases the amount of force loss and the vehicle traction decreases drastically. This condition is caused by the phenomenon of slipping, which, in addition to the waste of energy produced, causes the premature wear of driving tires. It also causes the temperature of the transmission oil to rise too much, as a result, causes a reduction in the quality and become dirty to oil and also reduces the useful life of the clutches disk and plates inside the transmission. this issue is much more important in road construction and mining machinery than passenger vehicles and is always one of the most important and significant issues in the design discussion, in order to overcome. One of these methods is the automatic spin regulator system which is abbreviated as ASR. The importance of this method and its structure and function have solved one of the biggest challenges of the powertrain system in the field of construction and mining machinery. That this research is examined.Keywords: automatic spin regulator, ASR, methods of reducing slipping, methods of preventing the reduction of the useful life of clutches disk and plate, methods of preventing the premature dirtiness of transmission oil, method of preventing the reduction of the useful life of tires
Procedia PDF Downloads 799566 The Voice Rehabilitation Program Following Ileocolon Flap Transfer for Voice Reconstruction after Laryngectomy
Authors: Chi-Wen Huang, Hung-Chi Chen
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Total laryngectomy affects swallowing, speech functions and life quality in the head and neck cancer. Voice restoration plays an important role in social activities and communication. Several techniques have been developed for voice restoration and reported to improve the life quality. However, the rehabilitation program for voice reconstruction by using the ileocolon flap still unclear. A retrospective study was done, and the patients' data were drawn from the medical records between 2010 and 2016 who underwent voice reconstruction by ileocolon flap after laryngectomy. All of them were trained to swallow first; then, the voice rehabilitation was started. The outcome of voice was evaluated after 6 months using the 4-point scoring scale. In our result, 9.8% patients could give very clear voice so everyone could understand their speech, 61% patients could be understood well by families and friends, 20.2% patients could only talk with family, and 9% patients had difficulty to be understood. Moreover, the 57% patients did not need a second surgery, but in 43% patients voice was made clear by a second surgery. In this study, we demonstrated that the rehabilitation program after voice reconstruction with ileocolon flap for post-laryngectomy patients is important because the anatomical structure is different from the normal larynx.Keywords: post-laryngectomy, ileocolon flap, rehabilitation, voice reconstruction
Procedia PDF Downloads 1569565 Relevance of Dosing Time for Everolimus Toxicity in Respect to the Circadian P-Glycoprotein Expression in Mdr1a::Luc Mice
Authors: Narin Ozturk, Xiao-Mei Li, Sylvie Giachetti, Francis Levi, Alper Okyar
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P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity.Keywords: circadian rhythm, chronotoxicity, everolimus, mdr1a::Luc mice, p-glycoprotein
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