Search results for: death practices

Authors: Junaid Mahmood Alam

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Revalidating and harmonizing clinical chemistry analytical principles and optimizing methods through quality control programs and assessments is the preeminent means to attain optimal outcome within the clinical laboratory services. Present study reports revalidation of our existing IFCC regularized analytical methods, particularly hepatic and thyroid function tests, by optimization of precision analyses and processing through external and internal quality assessments and regression determination. Parametric components of hepatic (Bilirubin ALT, γGT, ALP), cardiac (LDH, AST, Trop I) and thyroid/pituitary (T3, T4, TSH, FT3, FT4) function tests were used to validate analytical techniques on automated chemistry and immunological analyzers namely Hitachi 912, Cobas 6000 e601, Cobas c501, Cobas e411 with UV kinetic, colorimetric dry chemistry principles and Electro-Chemiluminescence immunoassay (ECLi) techniques. Process of validation and revalidation was completed with evaluating and assessing the precision analyzed Preci-control data of various instruments plotting against each other with regression analyses R2. Results showed that: Revalidation and optimization of respective parameters that were accredited through CAP, CLSI and NEQAPP assessments depicted 99.0% to 99.8% optimization, in addition to the methodology and instruments used for analyses. Regression R2 analysis of BilT was 0.996, whereas that of ALT, ALP, γGT, LDH, AST, Trop I, T3, T4, TSH, FT3, and FT4 exhibited R2 0.998, 0.997, 0.993, 0.967, 0.970, 0.980, 0.976, 0.996, 0.997, 0.997, and R2 0.990, respectively. This confirmed marked harmonization of analytical methods and instrumentations thus revalidating optimized precision standardization as per IFCC recommended guidelines. It is concluded that practices of revalidating and harmonizing the existing or any new services should be followed by all clinical laboratories, especially those associated with tertiary care hospital. This is will ensure deliverance of standardized, proficiency tested, optimized services for prompt and better patient care that will guarantee maximum patients’ confidence.

Keywords: revalidation, standardized, IFCC, CAP, harmonized

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Authors: Xiaoqin Wang, Li Yin

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Background and purpose: In many practices, one estimates causal effects arising from a complex stochastic process, where a sequence of treatments are assigned to influence a certain outcome of interest, and there exist time-dependent covariates between treatments. When covariates are plentiful and/or continuous, statistical modeling is needed to reduce the huge dimensionality of the problem and allow for the estimation of causal effects. Recently, Wang and Yin (Annals of statistics, 2020) derived a new general formula, which expresses these causal effects in terms of the point effects of treatments in single-point causal inference. As a result, it is possible to conduct the modeling via point effects. The purpose of the work is to study the modeling of these causal effects via point effects. Challenges and solutions: The time-dependent covariates often have influences from earlier treatments as well as on subsequent treatments. Consequently, the standard parameters – i.e., the mean of the outcome given all treatments and covariates-- are essentially all different (null paradox). Furthermore, the dimension of the parameters is huge (curse of dimensionality). Therefore, it can be difficult to conduct the modeling in terms of standard parameters. Instead of standard parameters, we have use point effects of treatments to develop likelihood-based parametric approach to the modeling of these causal effects and are able to model the causal effects of a sequence of treatments by modeling a small number of point effects of individual treatment Achievements: We are able to conduct the modeling of the causal effects from a sequence of treatments in the familiar framework of single-point causal inference. The simulation shows that our method achieves not only an unbiased estimate for the causal effect but also the nominal level of type I error and a low level of type II error for the hypothesis testing. We have applied this method to a longitudinal study of COVID-19 mortality among Scandinavian countries and found that the Swedish approach performed far worse than the other countries' approach for COVID-19 mortality and the poor performance was largely due to its early measure during the initial period of the pandemic.

Keywords: causal effect, point effect, statistical modelling, sequential causal inference

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Authors: Archana Soni, Arvind Mittal, Manmohan Kapshe

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Energy has been recognized as one of the key inputs for the economic growth and social development of a country. High economic growth naturally means a high level of energy consumption. However, in the present energy scenario where there is a wide gap between the energy generation and energy consumption, it is extremely difficult to match the demand with the supply. India being one of the largest and rapidly growing developing countries, there is an impending energy crisis which requires immediate measures to be adopted. In this situation, the concept of Energy Intensity comes under special focus to ensure energy security in an environmentally sustainable way. Energy Intensity is defined as the energy consumed per unit output in the context of industrial energy practices. It is a key determinant of the projections of future energy demands which assists in policy making. Energy Intensity is inversely related to energy efficiency; lesser the energy required to produce a unit of output or service, the greater is the energy efficiency. Energy Intensity of Indian manufacturing industries is among the highest in the world and stands for enormous energy consumption. Hence, reducing the Energy Intensity of Indian manufacturing industries is one of the best strategies to achieve a low level of energy consumption and conserve energy. This study attempts to analyse the factors which influence the Energy Intensity of Indian manufacturing firms and how they can be used to reduce the Energy Intensity. The paper considers six of the largest energy consuming manufacturing industries in India viz. Aluminium, Cement, Iron & Steel Industries, Textile Industries, Fertilizer and Paper industries and conducts a detailed Energy Intensity analysis using the data from PROWESS database of the Centre for Monitoring Indian Economy (CMIE). A total of twelve independent explanatory variables based on various factors such as raw material, labour, machinery, repair and maintenance, production technology, outsourcing, research and development, number of employees, wages paid, profit margin and capital invested have been taken into consideration for the analysis.

Keywords: energy intensity, explanatory variables, manufacturing industries, PROWESS database

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Authors: Rameh Chauhan

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Tunnel construction in Himalayan rock is a challenging task due to fragile nature of the strata. Tunnel excavation carried out from lower Himalayas to high Himalayas in different metamorphic rock. Therefore application of engineering geology plays a vital role during various stage of the tunneling projects. Engineering geology is defined as application of geology to construction of civil structures through engineering practice. It is applied to the design, construction and performance aspects of engineering structure on the surface or sub-surface like dam, underground and surface power house, cut slopes, tunnels and underground storage cavern for nuclear material. But this paper emphasized mostly on underground structures like big caverns of Power house, desilting chambers, and tunnels of various sizes. Construction of these structures in the fragile rock conditions of Himalayan geology from Western Himalayas to Eastern Himalayas necessitated the application of the engineering geology on the micro-scale base for the stability, performance, and longevity of the civil structures. Number of hydropower projects have been constructed, some of them are under construction and under investigation stage. These projects are located in various parts of Himalayas under various seismic-tectonic zones. Tunneling works are involved in these projects. This paper represents the various engineering geological practices adopted in investigation and construction stage of various projects based on experiences gained during past construction histories in Himalayan geology of young mountains in very fragile geological conditions. Highlighting and sharing of use of these techniques on various platforms will definitely enhance the knowledge for carrying out the construction of various projects for the development of society. Construction of the tunnels, surface, and sub-surface caverns, dams, highway, metro, highway tunnels are all based on engineering geological parameters in combinations with other engineering considerations.

Keywords: cavern-power house, desilting chambers and tunnels, seismic-tectonic-zones, earthquake-prone zones based on intensities

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Authors: Shawna Staud, Mary Kaye Scaramucci

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Objective: Rubber cup polishing has been a traditional method of preventative therapy in dental hygiene treatment. Newer methods such as air polishing have changed the way dental hygiene care is provided, yet this technique has not been embraced by students in the program nor by practitioners in the workforce. Students entering the workforce tend to follow office protocol and are limited in confidence to introduce technologies learned in the curriculum. This project was designed to help students gain confidence in newer skills and encourage private practice settings to adopt newer technologies for patient care. Our program recently introduced air polishing earlier in the program before the rubber cup technique to determine if students would embrace the technology to become leading-edge professionals when they enter the marketplace. Methods: The class of 2022 was taught the traditional method of polishing in the first-year curriculum and air polishing in the second-year curriculum. The class of 2023 will be taught the air polishing method in the first-year curriculum and the traditional method of polishing in the second-year curriculum. Pre- and post-graduation survey data will be collected from both cohorts. Descriptive statistics and pre and post-paired t-tests with alpha set at .05 to compare pre and post-survey results will be used to assess data. Results: This study is currently in progress, with a completion date of October 2023. The class of 2022 completed the pre-graduation survey in the spring of 2022. The post-gradation survey will be sent out in October 2022. The class of 2023 cohort will be surveyed in the spring of 2023 and October 2023. Conclusion: Our hypothesis is students who are taught air polishing first will be more inclined to adopt that skill in private practice, thereby embracing newer technology and improving oral health care.

Keywords: luggage handling system at world’s largest pilgrimage center

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Authors: Lotsmart Fonjong

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The livelihood of rural communities in the West African state of Cameroon, which is largely dictated by natural forces (rainfall, temperatures, and soil), is today threatened by climate change and armed conflict. This paper investigates the extent to which rural communities are aware of climate change, how their perceptions of changes across different agro-ecological zones have impacted farming practices, output, and lifestyles, on the one hand, and the extent to which local armed conflicts are confounding their efforts and adaptation abilities. The paper is based on a survey conducted among small farmers in selected localities within the forest and savanna ecological zones of the conflict-ridden Northwest and Southwest Cameroon. Attention is paid to farmers’ gender, scale, and type of farming. Farmers’ perception of/and response to climate change are analysed alongside local rainfall and temperature data and mobilization for climate justice. Findings highlight the fact that farmers’ perception generally corroborates local climatic data. Climatic instability has negatively affected farmers’ output, food prices, standards of living, and food security. However, the vulnerability of the population varies across ecological zones, gender, and crop types. While these factors also account for differences in local response and adaptation to climate change, ongoing armed conflicts in these regions have further complicated opportunities for climate-driven agricultural innovations, inputs, and exchange of information among farmers. This situation underlines how poor communities, as victims, are forced into many complex problems outsider their making. It is therefore important to mainstream farmers’ perceptions and differences into policy strategies that consider both climate change and Anglophone conflict as national security concerns foe sustainable development in Cameroon.

Keywords: adaptation policies, climate change, conflict, small farmers, cameroon

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Authors: Lara Al-Haddad, Mark Whittington

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This paper aims to examine the impact of two influential internal corporate governance mechanisms, namely board characteristics and ownership structure on the use of real activities-based and accrual-based earnings management by Jordanian public firms. Using panel data from Jordanian public firms after the introduction of the Jordanian Corporate Governance Code (JCGC) in 2009, the study finds both institutional ownership and managerial ownership constrain the use of real and accrual earnings manipulations. On the other side, both independent directors and largest shareholders are found to exaggerate the incidence of using real and accrual earnings management. The study also examines the trade-off between real and accrual earnings management and found that Jordanian firms use a combination of real and accrual-based earnings management to obtain the greatest effect on earnings reporting strategies. For the purpose of this study, three types of real earnings management are considered: sales manipulation, overproduction, and the abnormal reduction of discretionary expenditures. The abnormal discretionary accrual is considered for accruals management. While for the internal corporate governance mechanisms; board characteristics are examined by using board independence, board size, and CEO-duality; and ownership structure is examined by using managerial ownership, institutional ownership, foreign ownership and largest shareholder ownership. To the best knowledge of the researchers, this study is the first to examine the relationship between board characteristics and real earnings management in Jordan. Further, it is the first to examine the relationship between corporate governance mechanisms and discretionary accruals after the introduction of the Jordanian Corporate Governance Code in 2009. Thus, the findings of this study have important policy implications for policymakers, regulators, standard setters, audit professional, and investors in their attempts to constrain the practice of earnings management, whether real or accrual, and to improve the financial reporting quality in Jordan.

Keywords: board characteristics, Jordan, ownership structure, real earnings management

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Authors: Ali A. Bazzi, Ameer Hamza, Riley O’Hara, Kimberly Kado, Karen H. Hagglund, Lamia Fathallah, Robert T. Morris

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Introduction: Endometrial Cancer is a common gynecologic malignancy primarily treated with complete surgical staging, which may include complete pelvic and para-aortic lymphadenectomy. The role of lymphadenectomy is controversial, especially the intraoperative indications for the procedure. Three factors are important in decision to proceed with lymphadenectomy: Myometrial invasion, maximum tumor dimension, and histology. Many institutions incorporate these criteria in varying degrees in the decision to proceed with lymphadenectomy. This investigation assesses the use of intraoperatively measured MTD with and without pre-operative histologic grade. Methods: This study compared retrospectively EEC patients with intraoperatively measured MTD ≤2 cm to those with MTD >2 cm from January 1, 2002 to August 31, 2017. This assessment compared those with MTD ≤ 2cm with endometrial biopsy (EB) grade 1-2 to patients with MTD > 2cm with EB grade 3. Lymph node metastasis (LNM), recurrence, and survival were compared in these groups. Results: This study reviewed 222 patient cases. In tumors > 2 cm, LNM occurred in 20% cases while in tumors ≤ 2 cm, LNM was found in 6% cases (p=0.04). Recurrence and mean survival based on last follow up visit in these two groups were not statistically different (p=0.78 and 0.36 respectively). Data demonstrated a trend that when combined with preoperative EB International Federation of Gynecology and Obstetrics (FIGO) grade, a higher proportion of patients with EB FIGO Grade 3 and MTD > 2 cm had LNM compared to those with EB FIGO Grade 1-2 and MTD ≤ 2 cm (43% vs, 11%, p=0.06). LNM was found in 15% of cases in which lymphadenectomy was performed based on current practices, whereas if the criteria of EB FIGO 3 and MTD > 2 cm were used the incidence of LNM would have been 44% cases. However, using this criterion, two patients would not have had their nodal metastases detected. Compared to the current practice, the sensitivity and specificity of the proposed criteria would be 60% and 81%, respectively. The PPV and NPV would be 43% and 90%, respectively. Conclusion: The results indicate that MTD combined with EB FIGO grade can detect LNM in a higher proportion of cases when compared to current practice. MTD combined with EB FIGO grade may eliminate the need of frozen section sampling in a substantial number of cases.

Keywords: endometrial cancer, FIGO grade, lymphadenectomy, tumor size

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Authors: Shivani Dolas, A. Richa Mishra

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The existence of Courtyards in India can be traced back to ‘Indus valley civilization’ and various layers of history bearing implications like socio-cultural, traditional, religious, climatic, etc., moreover serving as a breathing space in case of historical core areas. Over time, with the overlay of various historic layers within the historic urban cores and the present high density populace, the cores are getting congested day by day. In this case, courtyards may emerge out as an efficient medium to provide quality of life through livable spaces. Presently, with the growing population of the historic town of Gwalior, town in Madhya Pradesh holds remarkable essence of courtyards with its multiple concepts over time. Its scale and function varies from an imposing grand appearance in palatial form, up to functional practices as residential. Its privilege can also be drawn in urban forms, in sharing single space by multiple dwellings and in temples which can be sketched specifically in the region. Moreover, the effectiveness of courtyards has proven balance and control of micro-climate in such composite climate region. The research paper aims to underline the concept of courtyards in case of a mixed use neighborhood, Naya bazar, in Lashkar area of Gwalior, which developed during 19th century, highlighting the need of its preservation. The paper also elaborates its various implications on user-space relationship as in the present context, and growing congestion in the area, user and space relationship is seen lost. The noticeable change in the behavioral context in buildings and users can be noticed with the downfall of courtyards, isolating users with land. Also, a concern has been expressed on negligence of courtyard planning in future development, suggesting recommendations on preserving the courtyard typology as heritage.

Keywords: courtyards, Gwalior, historic settlement, heritage

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Authors: Christie DeGregorio

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In today's rapidly evolving educational landscape, adult learners are becoming an increasingly significant demographic. These individuals often possess a wealth of life experiences and diverse interests that can greatly influence their learning styles. Recognizing and incorporating these interests into educational practices can lead to enhanced engagement, motivation, and overall learning outcomes for adult learners. This essay aims to explore the significance of incorporating adult learners' interests into learning styles and provide an overview of the methodologies used in related studies. When investigating the incorporation of adult learners' interests into learning styles, researchers have employed various methodologies to gather valuable insights. These methodologies include surveys, interviews, case studies, and classroom observations. Surveys and interviews allow researchers to collect self-reported data directly from adult learners, providing valuable insights into their interests, preferences, and learning styles. Case studies offer an in-depth exploration of individual adult learners, highlighting how their interests can be integrated into personalized learning experiences. Classroom observations provide researchers with a firsthand understanding of the dynamics between adult learners' interests and their engagement within a learning environment. The major findings from studies exploring the incorporation of adult learners' interests into learning styles reveal the transformative impact of this approach. Firstly, aligning educational content with adult learners' interests increases their motivation and engagement in the learning process. By connecting new knowledge and skills to topics they are passionate about, adult learners become active participants in their own education. Secondly, integrating interests into learning styles fosters a sense of relevance and applicability. Adult learners can see the direct connection between the knowledge they acquire and its real-world applications, which enhances their ability to transfer learning to various contexts. Lastly, personalized learning experiences tailored to individual interests enable adult learners to take ownership of their educational journey, promoting lifelong learning habits and self-directedness.

Keywords: integration, personalization, transferability, learning style

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Authors: Nikolai Bertelsen, Robert A. Alphinas, Klaus B. Orskov

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The shortest possible tool stickout has been the traditional go-to approach with expectations of increased stability and productivity. However, experimental studies at Danish Advanced Manufacturing Research Center (DAMRC) have proven that for some tool stickout lengths, there exist local productivity optimums when utilizing the Stability Lobe Diagrams for chatter avoidance. This contradicts with traditional logic and the best practices taught to machinists. This paper explores the vibrational characteristics and behaviour of a milling system over the tool stickout length. The experimental investigation has been conducted by tap testing multiple endmills where the tool stickout length has been varied. For each length, the modal parameters have been recorded and mapped to visualize behavioural tendencies. Furthermore, the paper explores the correlation between the modal parameters and the Stability Lobe Diagram to outline the influence and importance of each parameter in a multi-mode system. The insights are conceptualized into a tool tuning approximation solution. It builds on an almost linear change in the natural frequencies when amending tool stickout, which results in changed positions of the Chatter-free Stability Lobes. Furthermore, if the natural frequency of two modes become too close, it will onset of the dynamic absorber effect phenomenon. This phenomenon increases the critical stable depth of cut, allowing for a more stable milling process. Validation tests on the tool tuning approximation solution have shown varying success of the solution. This outlines the need for further research on the boundary conditions of the solution to understand at which conditions the tool tuning approximation solution is applicable. If the conditions get defined, the conceptualized tool tuning approximation solution outlines an approach for quick and roughly approximating tool stickouts with the potential for increased stiffness and optimized productivity.

Keywords: milling, modal parameters, stability lobes, tap testing, tool tuning

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Authors: Sheikh Omar Sillah

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Introduction: Monitoring is an important means of ensuring the smooth implementation and quality of clinical trials. For many years, traditional site monitoring approaches have been critical in detecting data errors but not optimal in identifying fabricated and implanted data as well as non-random data distributions that may significantly invalidate study results. The objective of this paper was to provide recommendations based on best statistical monitoring practices for detecting data-integrity issues suggestive of fabrication and implantation early in the study conduct to allow implementation of meaningful corrective and preventive actions. Methodology: Electronic bibliographic databases (Medline, Embase, PubMed, Scopus, and Web of Science) were used for the literature search, and both qualitative and quantitative studies were sought. Search results were uploaded into Eppi-Reviewer Software, and only publications written in the English language from 2012 were included in the review. Gray literature not considered to present reproducible methods was excluded. Results: A total of 18 peer-reviewed publications were included in the review. The publications demonstrated that traditional site monitoring techniques are not efficient in detecting data anomalies. By specifying project-specific parameters such as laboratory reference range values, visit schedules, etc., with appropriate interactive data monitoring, statistical monitoring can offer early signals of data anomalies to study teams. The review further revealed that statistical monitoring is useful to identify unusual data patterns that might be revealing issues that could impact data integrity or may potentially impact study participants' safety. However, subjective measures may not be good candidates for statistical monitoring. Conclusion: The statistical monitoring approach requires a combination of education, training, and experience sufficient to implement its principles in detecting data anomalies for the statistical aspects of a clinical trial.

Keywords: statistical monitoring, data anomalies, clinical trials, traditional monitoring

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Authors: S. K. Kakraliya, H. S. Jat, Manish Kakraliya, P. C. Sharma, M. L. Jat

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The biggest challenge in agriculture is to produce more food for the continually increasing world population with in the limited land and water resources. Serious water deficits and reducing natural resources are some of the major threats to the agricultural sustainability in many regions of South Asia. Food and water security may be gained by bringing improvement in the crop water productivity and the amount produced per unit of water consumed. Improvement in the crop water productivity may be achieved by pursuing alternative modern agronomics approaches, which are more friendly and efficient in utilizing natural resources. Therefore, a research trial on conservation agriculture (CA) and precision water management (PWM) was conducted in 2018-19 at Karnal, India to evaluate the effect on crop productivity and irrigation in sodic soils under rice-wheat (RW) systems of Indo-Gangetic Plains (IGP). Eight scenarios were compared varied in the tillage, crop establishment, residue and irrigarion management i.e., {First four scenarios irrigated with flood irrigation method;Sc1-Conventional tillage (CT) without residue, Sc2-CT with residue, Sc3- Zero tillage (ZT) without residue, Sc4-ZT with residue}, and {last four scenarios irrigated with sub-surface drip irrigation method; Sc5-ZT without residue, Sc6- ZT with residue, Sc7-ZT inclusion legume without residue and Sc8- ZT inclusion legume with residue}. Results revealed that CA-flood irrigation (S3, Sc4) and CA-PWM system (Sc5, Sc6, Sc7 and Sc8) recorded about ~5% and ~15% higher wheat yield, respectively compared to Sc1. Similar, CA-PWM saved ~40% irrigation water compared to Sc1. Rice yield was not different under different scenarios in the first year (kharif 2019) but almost half irrigation water saved under CA-PWM system. Therefore, results of our study on modern agronomic practices including CA and precision water management (subsurface drip irrigation) for RW rotation would be addressed the existing and future challenges in the RW system.

Keywords: Sub-surface drip, Crop residue, Crop yield , Zero tillage

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Authors: Yin Ma, Xun Wang, Kelsey Austin

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Purpose – Building upon career construction theory and the conservation of resources theory, we developed a moderated mediation model to examine how the perceived university support impact students’ career adapting responses, namely, crystallization, exploration, decision and preparation, via the mediator career adaptability and moderator perceived parental support. Design/methodology/approach – The multi-stage sampling strategy was employed and survey data were collected. Structural equation modeling was used to perform the analysis. Findings – Perceived university support could directly promote students’ career adaptability, and promote three career adapting responses, namely, exploration, decision and preparation. It could also impact four career adapting responses via mediation effect of career adaptability. Its impact on students’ career adaptability can greatly increase when students’ receive parental related career support. Research limitations/implications – The cross-sectional design limits causal inference. Conducted in China, our findings should be cautiously interpreted in other countries due to cultural differences. Practical implications – University support is vital to students’ career adaptability and supports from parents can enhance this process. University-home collaboration is necessary to promote students’ career adapting responses. For students, seeking and utilizing as much supporting resources as possible is vital for their human resources development. On an organizational level, universities could benefit from our findings by introducing the practices which ask students to rate the career-related courses and encourage them to chat with parents regularly. Originality/ value – Using recently developed scale, current work contributes to the literature by investigating the impact of multiple contextual factors on students’ career adapting response. It also provide the empirical support for the role of human intervention in fostering career adapting responses.

Keywords: career adapability, university and parental support, China studies, sociology of education

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Authors: Onosedeba Mary Ayayia

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Inclusive education has emerged as a critical global imperative, aiming to provide equitable educational opportunities for all, regardless of their abilities or disabilities. In Africa, the pursuit of inclusive education faces significant challenges, particularly concerning the development and implementation of inclusive curricula tailored to the diverse needs of students with disabilities. This study delves into the heart of this issue, seeking to address the pressing problem of exclusion and marginalization of students with disabilities in mainstream educational systems across the continent. The problem is complex, entailing issues of limited access to tailored curricula, shortages of qualified teachers in special needs education, stigmatization, limited research and data, policy gaps, inadequate resources, and limited community awareness. These challenges perpetuate a system where students with disabilities are systematically excluded from quality education, limiting their future opportunities and societal contributions. This research proposes a comprehensive examination of the current state of inclusive curriculum development and implementation in Africa. Through an innovative and explicit exploration of the problem, the study aims to identify effective strategies, guidelines, and best practices that can inform the development of inclusive curricula. These curricula will be designed to address the diverse learning needs of students with disabilities, promote teacher capacity building, combat stigmatization, generate essential data, enhance policy coherence, allocate adequate resources, and raise community awareness. The goal of this research is to contribute to the advancement of inclusive education in Africa by fostering an educational environment where every student, regardless of ability or disability, has equitable access to quality education. Through this endeavor, the study aligns with the broader global pursuit of social inclusion and educational equity, emphasizing the importance of inclusive curricula as a foundational step towards a more inclusive and just society.

Keywords: inclusive education, special education, curriculum development, Africa

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Authors: Danielle Katrina Santos, Koji Shimada

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Environmentally-friendly agriculture has been promoted for over two decades as a response to the environmental challenges brought by climate change and biological loss. Located above the equator, it is possible that Japan may benefit from future climate change, yet Japan is also a rarely developed country located in the Asian Monsoon climate region, making it vulnerable to the impacts of climate change. In this regard, the Japanese government has initiated policies to adapt to the adverse effects of climate change through the promotion and popularization of environmentally-friendly farming practices. This study aims to determine profit efficiency among environmentally-friendly rice farmers in Shiga Prefecture using the Stochastic Frontier Approach. A cross-sectional survey was conducted among 66 farmers from top rice-producing cities through a structured questionnaire. Results showed that the gross farm income of environmentally-friendly rice farmers was higher by JPY 316,223.00/ha. Production costs were also found to be higher among environmentally-friendly rice farmers, especially on labor costs, which accounted for 32% of the total rice production cost. The resulting net farm income of environmentally-friendly rice farmers was only higher by JPY 18,044/ha. Results from the stochastic frontier analysis further showed that the profit efficiency of conventional farmers was only 69% as compared to environmentally-friendly rice farmers who had a profit efficiency of 76%. Furthermore, environmentally-friendly agriculture participation, other types of subsidy, educational level, and farm size were significant factors positively influencing profit efficiency. The study concluded that substitution of environmentally-friendly agriculture for conventional rice farming would result in an increased profit efficiency due to the direct payment subsidy and price premium received. The direct government policies that would strengthen the popularization of environmentally-friendly agriculture to increase the production of environmentally-friendly products and reduce pollution load to the Lake Biwa ecosystem.

Keywords: profit efficiency, environmentally-friendly agriculture, rice farmers, direct payment subsidies

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Authors: Nabil Elkhatri, Mohamed Louay Metougui, Ngonidzashe Chirinda

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Mining activities have left a legacy of degraded landscapes, prompting urgent efforts for ecological restoration. Reforestation holds promise as a potent tool to rehabilitate these old mining sites, with the potential to sequester carbon and contribute to climate change mitigation. This study focuses on evaluating the carbon stock and sequestration potential of reforestation species in the context of Morocco's mining areas, employing the DeNitrification-DeComposition (DNDC) model. The research is grounded in recognizing the need to connect theoretical models with practical implementation, ensuring that reforestation efforts are informed by accurate and context-specific data. Field data collection encompasses growth patterns, biomass accumulation, and carbon sequestration rates, establishing an empirical foundation for the study's analyses. By integrating the collected data with the DNDC model, the study aims to provide a comprehensive understanding of carbon dynamics within reforested ecosystems on old mining sites. The major findings reveal varying sequestration rates among different reforestation species, indicating the potential for species-specific optimization of reforestation strategies to enhance carbon capture. This research's significance lies in its potential to contribute to sustainable land management practices and climate change mitigation strategies. By quantifying the carbon stock and sequestration potential of reforestation species, the study serves as a valuable resource for policymakers, land managers, and practitioners involved in ecological restoration and carbon management. Ultimately, the study aligns with global objectives to rejuvenate degraded landscapes while addressing pressing climate challenges.

Keywords: carbon stock, carbon sequestration, DNDC model, ecological restoration, mining sites, Morocco, reforestation, sustainable land management.

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Authors: Tugce Arslan

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For a communicative act to be carried out successfully, the speaker and the listener must consider certain principles in line with the intention–centered “Cooperative Principle” expressed by H. P. Grice. Violation of a communication principle causes the listener to make new inferences called “implicatures”. In this study, focusing on the linguistic use of H. P. Grice’s principles, we aim to find out which principles of conversation are generally followed in case files from different fields and which principles are frequently violated. Three case files were examined, and the violating and the abiding cases of the maxims were classified in terms of four categories (Quality, Quantity, Relevance and Manner). The results of this investigation is reported below (V: Violating, A: Abiding): Quality Quantity Relevance Manner V A V A V A V A Case 1 10 8 5 9 3 15 16 6 Case 2 4 5 11 6 2 11 7 14 Case 3 21 13 7 12 9 14 15 9 Total 35 26 23 27 14 40 38 29 The excerpts were selected from files covering three different areas: the Assize Court, the Family Court and the Commercial Court of First Instance. In this way, the relations between the types of violations and the types of courts are examined. Our main finding is that in the 1st and the 3rd file, as the cases of violation in “Quality” and “Manner” increase, the cases of violation in “Quantity” and “Relevance” decrease. In the second file, on the other hand, as the cases of violation in “Quantity” increase, the cases of violation in “Quality”, “Relevance” and “Manner” decrease. In the talk, we shall compare these results with the results obtained in the study of Tajabadi, Dowlatabadi, and Mehric (2014), which examined various case files in Iran. Our main finding is that in the study conducted in Iran, violations were found only on the principles of “Quantity” and “Relevance”, while violations were found on the principles of “Quality”, “Quantity” and “Manner” in this study. In this case, it shows us that there is a connection between at least two maxims. In both cases, it has been noticed that the “Quantity” maxim is a common denominator. Studies in this field can be enlightening for many areas such as discourse analysis, legal studies, etc. Accordingly, comments will be made about the nature of the violations mentioned in H. P. Grice’s “Cooperation Principle”. We shall also discuss various conversational practices that cannot be analysed with these maxims.

Keywords: comparative analysis, cooperation principle, forensic linguistics, pragmatic.

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Authors: Vinti Davar

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Introduction: Childhood overweight increases the risk for certain medical and psychological conditions. Millions of school-age children worldwide are affected by serious yet easily treatable and preventable illnesses that inhibit their ability to learn. Healthier children stay in school longer, attend more regularly, learn more and become healthier and more productive adults. Schools are an important setting for nutrition education because one can reach most children, teachers and parents. These years offer a key window for shaping their lifetime habits, which have an impact on their health throughout life. Against this background, an attempt was made to impart nutrition education to school children in Haryana state of India to promote healthy food choices and assess the effectiveness of this program. Methodology: This study was completed in two phases. During the first phase, pre-intervention anthropometric and dietary survey was conducted; the teaching materials for nutrition intervention program were developed and tested; and the questionnaire was validated. In the second phase, an intervention was implemented in two schools of Kurukshetra, Haryana for six months by personal visits once a week. A total of 350 children in the age group of 6-12 years were selected. Out of these, 279 children, 153 boys and 126 girls completed the study. The subjects were divided into four groups namely: underweight, normal, overweight and obese based on body mass index-for-age categories. A power point colorful presentation to improve the quality of tiffin, snacks and meals emphasizing inclusion of all food groups especially vegetables every day and fruits at least 3-4 days per week was used. An extra 20 minutes of aerobic exercise daily was likewise organized and a healthy school environment created. Provision of clean drinking water by school authorities was ensured. Selling of soft drinks and energy-dense snacks in the school canteen as well as advertisements about soft drink and snacks on the school walls were banned. Post intervention, anthropometric indices and food selections were reassessed. Results: The results of this study reiterate the critical role of nutrition education and promotion in improving the healthier food choices by school children. It was observed that normal, overweight and obese children participating in nutrition education intervention program significantly (p≤0.05) increased their daily seasonal fruit and vegetable consumption. Fat and oil consumption was significantly reduced by overweight and obese subjects. Fast food intake was controlled by obese children. The nutrition knowledge of school children significantly improved (p≤0.05) from pre to post intervention. A highly significant increase (p≤0.00) was noted in the nutrition attitude score after intervention in all four groups. Conclusion: This study has shown that a well-planned nutrition education program could improve nutrition knowledge and promote positive changes in healthy food choices. A nutrition program inculcates wholesome eating and active life style habits in children and adolescents that could not only prevent them from chronic diseases and early death but also reduce healthcare cost and enhance the quality of life of citizens and thereby nations.

Keywords: children, eating habits healthy food, obesity, school going, fast foods

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Authors: P. Susheela, Mary Rosaline, R. Radha

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This research was designed to determine the bioactive compounds present in the nest samples of the mud dauber wasp, Sceliophron caementarium. Insects and insect-based products have been used for the treatment of various ailments from a very long time. It has been found that all over the world including the western societies and the indigenous populations, the usage of insect-based medicine plays an important role in various healing practices and magic rituals. Studies on the therapeutic usage of insects are negligible when compared to plants, the. In the present scenario, it is important to explore bioactive compounds from natural sources rather than depending on synthetic drugs that have adverse effects on human body. Keeping this in view, an attempt was made to analyze and identify bioactive components from the nest sample of the mud dauber wasp, Sceliophron caementarium. The nests of the mud dauber wasp, Sceliophron caementarium were collected from Coimbatore, Tamil Nadu, India. The nest sample was extracted with ethanol for 6-8 hours using Soxhlet apparatus. The final residue was obtained by filtering the extract through Whatman filter paper No.41. The GCMS analysis of the nest sample was performed using Perkin Elmer Elite - 5 capillary column. The resultant compounds were compared with the database of National Institute Standard and Technology (NIST), WILEY8, FAME. The GC-MS analysis of the concentrated ethanol extract revealed the presence of eight constituents like Methylene chloride, Eicosanoic acid, 1, 1’:3’, 1’’-Terphenyl, 5'-Phenyl, Di-N-Decylsulfone, 1, 2-Bis (Trimethylsilyl) Benzene, Androstane-11, 17-Dione, 3-[(Trimethylsilyl) Oxy]-, 17-[O-(Phenylmethyl) O. Most of the identified compounds were reported as having biological activities viz. anti-inflammatory, antibacterial and antifungal properties that can be of pharmaceutical importance and further study of these isolated compounds may prove their medicinal importance in future.

Keywords: Sceliophron caementarium, Gas chromatography-mass spectrometry, ethanol extract, bioactive compounds

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Authors: Simone Belli, Sergio Minniti, Valeria Santoro

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ICTs and technology transfer can benefit and move a country forward in economic and social development. However, ICT and access to the Internet have been inequitably distributed in most developing countries. In terms of science production and dissemination, this divide articulates itself also through the inequitable distribution of access to scientific knowledge and networks, which results in the exclusion of developing countries from the center of science. Developing countries are on the fringe of Science and Technology (S&T) production due not only to low investment in research but also to the difficulties to access international scholarly literature. In this respect, Open access (OA) initiatives and knowledge infrastructure represent key elements for both producing significant changes in scholarly communication and reducing the problems of developing countries. The spreading of the OA movement in the region, exemplified by the growth of regional and national initiatives, such as the creation of OA institutional repositories (e.g. SciELO and Redalyc) and the establishing of supportive governmental policies, provides evidence of the significant role that OA is playing in reducing the scientific gap between Latin American countries and improving their participation in the so-called ‘global knowledge commons’. In this paper, we map OA publications in Latin America and observe how Latin American countries are moving forward and becoming a leading force in widening access to knowledge. Our analysis, developed as part of the H2020 EULAC Focus research project, is based on mixed methods and consists mainly of a bibliometric analysis of OA publications indexed in the most important scientific databases (Web of Science and Scopus) and OA regional repositories, as well as the qualitative analysis of documents related to the main OA initiatives in Latin America. Through our analysis, we aim at reflecting critically on what policies, international standards, and best practices might be adapted to incorporate OA worldwide and improve the infrastructure of the global knowledge commons.

Keywords: open access, LAC countries, scientific publications, bibliometric analysis

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Authors: Mahera Abdulrahman, Satish Chandrasekhar Nair

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Growing demand for human health research in the United Arab Emirates (UAE) has prompted the need to develop a robust research ethics oversight, particularly given the large unskilled-worker immigrant population and the elderly citizens utilizing health services. Examination of the structure, function, practices and outcomes of the human research ethics committees (HREC) was conducted using two survey instruments, reliable and validated. Results indicate that in the absence of a national ethics regulatory body, the individual emirate’s governed 21 HRECs covering health facilities and academic institutions in the UAE. Among the HRECs, 86% followed International Council for Harmonization-Good Clinical Practice guidelines, 57% have been in operation for more than five years, 81% reviewed proposals within eight weeks, 48% reviewed for clinical and scientific merit apart from ethics, and 43% handled more than 50 research proposals per year. However, researcher recognition, funding transparency, adverse event reporting systems were widespread in less than one-third of all HRECs. Surprisingly, intellectual property right was not included as a research output. Research was incorporated into the vision and mission statements of many (62%) organizations and, mechanisms such as research publications, collaborations, and recognitions were employed as key performance indicators to measure research output. In spite, resources to generate research output such as dedicated budget (19%), support staff (19%) and continuous training and mentoring program for medical residents and HREC members were somehow lacking. HREC structure and operations in the UAE are similar to other regions of the world, resources allocation for efficient, quality monitoring, continuous training, and the creation of a clinical research network are needed to strengthen the clinical research enterprise to scale up for the future. It is anticipated that the results of this study will benefit investigators, regulators, pharmaceutical sponsors and the policy makers in the region.

Keywords: institutional review board, ethics committee, human research ethics, United Arab Emirates (UAE)

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Authors: Natasha Botha, Gary Corderely, Helen M. Inglis

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With the move to cleaner energy applications the transport industry is working towards on-board hydrogen, or compressed natural gas-fuelled vehicles. A popular method for storage is to use composite overwrapped pressure vessels (COPV) because of their high strength to weight ratios. The proper design of these COPVs are according to international standards; this study aims to provide a preliminary design for a 350 Bar Type IV COPV (i.e. a polymer liner with a composite overwrap). Netting analysis, a popular analytical approach, is used as a first step to generate an initial design concept for the composite winding. This design is further improved upon by following the American Society of Mechanical Engineers (ASME) Boiler and Pressure Vessel standards, Section X: Fibre-reinforced composite pressure vessels. A design program based on these two approaches is developed using Python. A numerical model of a burst test simulation is developed based on the two approaches and compared. The results indicate that the netting analysis provides a good preliminary design, while the ASME-based design is more robust and accurate as it includes a better approximation of the material behaviour. Netting analysis is an easy method to follow when considering an initial concept design for the composite winding when not all the material characteristics are known. Once these characteristics have been fully defined with experimental testing, an ASME-based design should always be followed to ensure that all designs conform to international standards and practices. Future work entails more detailed numerical testing of the design for improvement, this will include the boss design. Once finalised prototype manufacturing and experimental testing will be conducted, and the results used to improve on the COPV design.

Keywords: composite overwrapped pressure vessel, netting analysis, design, American Society of Mechanical Engineers section x, fiber-reinforced, hydrogen storage

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Authors: Merly Patiño Villanueva, Dubys Villarreal Torres, Eduardo Salazar Araujo, Lezly Ramos Macedo

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The concept of sustainability has been influencing business thinking from the perspective of various economic sectors and their environment, looking for concerns related to the risks associated with the indiscriminate consumption of the planet's resources, which have been widely studied and exposed by different public and private organizations. Tourism is not outsider to this reality; therefore, the concept of sustainable tourism evolves towards the integral management of resources, attending the needs of tourists, host communities and service providers, protecting ecosystems and assuring the conservation of the environment and its biodiversity. Considering the above, the purpose of this paper is to identify trends aimed at promoting sustainable tourism in the destinations of Barranquilla (Colombia) and Nayarit (Mexico). This study is part of the realistic epistemological paradigm, based on the existence of a specific environment for the development of tourism activity and the best sustainability practices associated with this industry, which can be observed and studied, therefore, this research contemplates qualitative research techniques such as the focus group and the interview, applied to 8 experts who are part of the value chain of the sector under study, added to a documentary review taken from the scientific databases Wos and Scopus, as well as statistical information published by official bodies. The data obtained were processed with the qualitative analysis software N-VIVO version 13. As a result, trends and actions to promote tourism are identified for the positioning of the cities of Barranquilla (Colombia) and Nayarit (Mexico) as sustainable destinations: first, the recovery of green areas and environmental spaces, as well as the realization of cultural events; promotion and encouragement of the creative industry and finally the realization of international events. It is concluded that both cities develop activities, projects and investments of public initiative, aimed at positioning them as sustainable tourist destinations.

Keywords: marketing, sustainability, tourism management, policies

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Authors: Eman. K. Ramadan, Abdelgawad. S. El-Tahawy

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The objective of this study was to evaluate the effects of calving season on the production and economic efficiency of dairy farms in Egypt. Our study was performed at dairy production farms in the Alexandria, Behera, and Kafr El-Sheikh provinces of Egypt from summer 2010 to winter 2013. The randomly selected dairy farms had herds consisting of Baladi, Holstein-Friesian, or cross-bred (Baladi × Holstein-Friesian) cows. The data were collected from production records and responses to a structured questionnaire. The average total return differed significantly (P < 0.05) between the different cattle breeds and calving seasons. The average total return was highest for the Holstein-Friesian cows that calved in the winter (29106.42 EGP/cow/year), and it was lowest for Baladi cows that calved in the summer (12489.79 EGP/cow/year). Differences in total returns between the cows that calved in the winter or summer or between the foreign and native breeds, as well as variations in calf prices, might have contributed to the differences in milk yield. The average net profit per cow differed significantly (P < 0.05) between the cattle breeds and calving seasons. The average net profit values for the Baladi cows that calved in the winter or summer were 2413 and 2994.96 EGP/cow/year, respectively, and those for the Holstein-Friesian cows were 10744.17 and 7860.56 EGP/cow/year, respectively, whereas those for the cross-bred cows were 10174.86 and 7571.33 EGP/cow/year, respectively. The variations in net profit might have resulted from variation in the availability or price of feed materials, milk prices, or sales volumes. Our results show that the breed and calving season of dairy cows significantly affected the economic efficiency of dairy farms in Egypt. The cows that calved in the winter produced more milk than those that calved in the summer, which may have been the result of seasonal influences, such as temperature, humidity, management practices, and the type of feed or green fodder available.

Keywords: calving season, economic, production, efficiency, dairy

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Authors: Kashi Raj Pandey

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Transformative learning is a form of learning rooted in learners' life experiences and their inherent love for learning. It emphasizes the importance of incorporating students' everyday work through the use of learning diaries and reflective journals. It encourages learners to take a proactive role in their own improvement, fostering creativity and promoting informed discussions about the learning process. Reflecting on the personal experience with English language learning in a rural village in Nepal where rote memorization was the prevailing teaching method, this traditional approach hindered a deeper understanding of the language, prompting the author to recognize the need for more effective pedagogy. In this study, the author delved into the cultural contextualization of English language learning, taking into account learners' backgrounds. The study’s findings highlighted the importance of equity, inclusion, mutuality, and social justice in the classroom, emphasizing the significance of integrating students' lived experiences into the pedagogical approach. This, in turn, can encourage students to engage in profound and collaborative learning practices within the realm of English language education. Upon successfully implementing the research findings, including the eight key conditions of transformative learning, in multiple classrooms, the author collaborated with international educationists and government stakeholders in Nepal. The purpose was to disseminate the research findings, conduct teacher training workshops, and systematically enhance Nepali students’ English language learning. These methods have already demonstrated a significant improvement in student engagement within the same school where the author once learned English as a child. This study aims to explore teachers’ decision-making process regarding the transition from traditional teaching methods to interactive ones, which have gained national recognition within the ESL/EFL teaching community in Nepal. By sharing these experiences, it is expected that other teachers will also contemplate adopting transformative learning pedagogy in their own classrooms.

Keywords: reflection, student engagement, pedagogy, transformative learning

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Authors: Babak Forouraghi

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A genetic circuit is a collection of interacting genes and proteins that enable individual cells to implement and perform vital biological functions such as cell division, growth, death, and signaling. In cell engineering, synthetic gene circuits are engineered networks of genes specifically designed to implement functionalities that are not evolved by nature. These engineered networks enable scientists to tackle complex problems such as engineering cells to produce therapeutics within the patient's body, altering T cells to target cancer-related antigens for treatment, improving antibody production using engineered cells, tissue engineering, and production of genetically modified plants and livestock. Construction of computational models to realize genetic circuits is an especially challenging task since it requires the discovery of flow of genetic information in complex biological systems. Building synthetic biological models is also a time-consuming process with relatively low prediction accuracy for highly complex genetic circuits. The primary goal of this study was to investigate the utility of a pre-trained bidirectional encoder transformer that can accurately predict gene expressions in genetic circuit designs. The main reason behind using transformers is their innate ability (attention mechanism) to take account of the semantic context present in long DNA chains that are heavily dependent on spatial representation of their constituent genes. Previous approaches to gene circuit design, such as CNN and RNN architectures, are unable to capture semantic dependencies in long contexts as required in most real-world applications of synthetic biology. For instance, RNN models (LSTM, GRU), although able to learn long-term dependencies, greatly suffer from vanishing gradient and low-efficiency problem when they sequentially process past states and compresses contextual information into a bottleneck with long input sequences. In other words, these architectures are not equipped with the necessary attention mechanisms to follow a long chain of genes with thousands of tokens. To address the above-mentioned limitations of previous approaches, a transformer model was built in this work as a variation to the existing DNA Bidirectional Encoder Representations from Transformers (DNABERT) model. It is shown that the proposed transformer is capable of capturing contextual information from long input sequences with attention mechanism. In a previous work on genetic circuit design, the traditional approaches to classification and regression, such as Random Forrest, Support Vector Machine, and Artificial Neural Networks, were able to achieve reasonably high R2 accuracy levels of 0.95 to 0.97. However, the transformer model utilized in this work with its attention-based mechanism, was able to achieve a perfect accuracy level of 100%. Further, it is demonstrated that the efficiency of the transformer-based gene expression classifier is not dependent on presence of large amounts of training examples, which may be difficult to compile in many real-world gene circuit designs.

Keywords: transformers, generative ai, gene expression design, classification

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Authors: Rani Fernandez

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As global concerns regarding environmental degradation and climate change intensify, the imperative for sustainable living has never been more critical. This research delves into the role of eco-products in everyday life as a pivotal strategy for achieving sustainability. The study investigates the awareness, adoption, and impact of eco-friendly products on individual and community levels. The research employs a mixed-methods approach, combining surveys, interviews, and case studies to explore consumer perceptions, behaviours, and motivations surrounding the use of eco-products. Additionally, life cycle assessments are conducted to evaluate the environmental footprint of selected eco-products, shedding light on their tangible contributions to sustainability. The findings reveal the diverse range of eco-products available in the market, from biodegradable packaging to energy-efficient appliances, and the extent to which consumers integrate these products into their daily routines. Moreover, the research examines the challenges and opportunities associated with widespread adoption, considering factors such as cost, accessibility, and efficacy. In addition to individual consumption patterns, the study investigates the broader societal impact of eco-product integration. It explores the potential for eco-products to drive systemic change by influencing supply chains, corporate practices, and government policies. The research highlights successful case studies of communities or businesses that have effectively incorporated eco-products, providing valuable insights into scalable models for sustainability. Ultimately, this research contributes to the discourse on sustainable living by elucidating the pivotal role of eco-products in shaping environmentally conscious behaviours. By understanding the dynamics of eco-product adoption, policymakers, businesses, and individuals can collaboratively work towards a more sustainable future. The implications of this study extend beyond academia, informing practical strategies for fostering a global shift towards sustainable consumption and production.

Keywords: eco-friendly, sustainablity, environment, climate change

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Authors: Hossein Afzali

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Increasingly, decision analytic models are used to inform decisions about whether or not to publicly fund new health technologies. It is well noted that the accuracy of model predictions is strongly influenced by the appropriateness of model structuring. However, there is relatively inadequate methodological guidance surrounding this issue in guidelines developed by national funding bodies such as the Australian Pharmaceutical Benefits Advisory Committee (PBAC) and The National Institute for Health and Care Excellence (NICE) in the UK. This presentation aims to discuss issues around model structuring within decision making with a focus on (1) the need for a transparent and evidence-based model structuring process to inform the most appropriate set of structural aspects as the base case analysis; (2) the need to characterise structural uncertainty (If there exist alternative plausible structural assumptions (or judgements), there is a need to appropriately characterise the related structural uncertainty). The presentation will provide an opportunity to share ideas and experiences on how the guidelines developed by national funding bodies address the above issues and identify areas for further improvements. First, a review and analysis of the literature and guidelines developed by PBAC and NICE will be provided. Then, it will be discussed how the issues around model structuring (including structural uncertainty) are not handled and justified in a systematic way within the decision-making process, its potential impact on the quality of public funding decisions, and how it should be presented in submissions to national funding bodies. This presentation represents a contribution to the good modelling practice within the decision-making process. Although the presentation focuses on the PBAC and NICE guidelines, the discussion can be applied more widely to many other national funding bodies that use economic evaluation to inform funding decisions but do not transparently address model structuring issues e.g. the Medical Services Advisory Committee (MSAC) in Australia or the Canadian Agency for Drugs and Technologies in Health.

Keywords: decision-making process, economic evaluation, good modelling practice, structural uncertainty

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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

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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.

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