Search results for: Gaussian Mixture Models
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 8244

Search results for: Gaussian Mixture Models

1104 Comparative Ante-Mortem Studies through Electrochemical Impedance Spectroscopy, Differential Voltage Analysis and Incremental Capacity Analysis on Lithium Ion Batteries

Authors: Ana Maria Igual-Munoz, Juan Gilabert, Marta Garcia, Alfredo Quijano-Lopez

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Nowadays, several lithium-ion battery technologies are being commercialized. These chemistries present different properties that make them more suitable for different purposes. However, comparative studies showing the advantages and disadvantages of different chemistries are incomplete or scarce. Different non-destructive techniques are currently being employed to detect how ageing affects the active materials of lithium-ion batteries (LIBs). For instance, electrochemical impedance spectroscopy (EIS) is one of the most employed ones. This technique allows the user to identify the variations on the different resistances present in LIBs. On the other hand, differential voltage analysis (DVA) has shown to be a powerful technique to detect the processes affecting the different capacities present in LIBs. This technique shows variations in the state of health (SOH) and the capacities for one or both electrodes depending on their chemistry. Finally, incremental capacity analysis (ICA) is a widely known technique for being capable of detecting phase equilibria. It reminds of the commonly used cyclic voltamperometry, as it allows detecting some reactions taking place in the electrodes. In these studies, a set of ageing procedures have been applied to commercial batteries of different chemistries (NCA, NMC, and LFP). Afterwards, results of EIS, DVA, and ICA have been used to correlate them with the processes affecting each cell. Ciclability, overpotential, and temperature cycling studies envisage how the charge-discharge rates, cut-off voltage, and operation temperatures affect each chemistry. These studies will serve battery pack manufacturers, as for common battery users, as they will determine the different conditions affecting cells for each of the chemistry. Taking this into account, each cell could be adjusted to the final purpose of the battery application. Last but not least, all the degradation parameters observed are focused to be integrated into degradation models in the future. This fact will allow the implementation of the widely known digital twins to the degradation in LIBs.

Keywords: lithium ion batteries, non-destructive analysis, different chemistries, ante-mortem studies, ICA, DVA, EIS

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1103 Open Innovation in SMEs: A Multiple Case Study of Collaboration between Start-ups and Craft Enterprises

Authors: Carl-Philipp Valentin Beichert, Marcel Seger

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Digital transformation and climate change require small and medium-sized enterprises (SME) to rethink their way of doing business. Inter-firm collaboration is recognized as helpful means of promoting innovation and competitiveness. In this context, collaborations with start-ups offer valuable opportunities through their innovative products, services, and business models. SMEs, and in particular German craft enterprises, play an important role in the country’s society and economy. Companies in this heterogeneous economic sector have unique characteristics and are limited in their ability to innovate due to their small size and lack of resources. Collaborating with start-ups could help to overcome these shortcomings. To investigate how collaborations emerge and what factors are decisive to successfully drive collaboration, we apply an explorative, qualitative research design. A sample of ten case studies was selected, with the collaboration between a start-up and a craft enterprise forming the unit of analysis. Semi-structured interviews with 20 company representatives allow for a two-sided perspective on the respective collaboration. The interview data is enriched by publicly available data and three expert interviews. As a result, objectives, initiation practices, applied collaboration types, barriers, as well as key success factors could be identified. The results indicate a three-phase collaboration process comprising an initiation, concept, and partner phase (ICP). The ICP framework proposed accordingly highlights the success factors (personal fit, communication, expertise, structure, network) for craft enterprises and start-ups for each collaboration phase. The role of a mediator in the start-up company, with strong expertise in the respective craft sector, is considered an important lever for overcoming barriers such as cultural and communication differences. The ICP framework thus provides promising directions for further research and can help practitioners establish successful collaborations.

Keywords: open innovation, SME, craft businesses, startup collaboration, qualitative research

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1102 Promising Anti-Displacement Practices for High Cost Cities

Authors: Leslie M. Mullins

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In the face of dramatically shifting demographic trends and macroeconomic pressures on affordable housing in high-cost cities, municipalities and developers have been forced to develop new models of sustainable development that integrates elements of substantial rehabilitation and new construction while controlling for relocation and mass displacement. Community development partners in the San Francisco Bay Area of Northern California are starting to prioritize anti-displacement strategies when rehabilitating severely neglected public housing developments. This study explored the community-driven efforts to transform four dilapidated public housing sites (N=2,600 households) into thriving mixed-income housing communities. Eight interviews were conducted with frontline workers (property managers and service providers), who directly worked with residents throughout critical stages of the relocation and leasing process. Interviews were audio-recorded, transcribed, and analyzed by a systematic procedure for qualitative analysis to identify key themes on the topics of interest. Also, an extensive literature analysis was conducted to determine promising practices throughout the industry. This study highlighted that resident’s emotional attachment to their homes (regardless of the deteriorating conditions of their unit) could both a) impede the relocation process and substantially impact the budget and timeline, while b) simultaneously providing a basis for an enhanced sense of belonging and community cohesion. This phenomenon often includes the welcoming of new residents and cultures. Resident centered workshops, healing centered rituals, and extensive 'hands-on' guidance was highlighted as promising practices that resulted in residential retention rates that were two to three times the national average and positively impacted the overall project’s budget and timeline.

Keywords: anti-displacement strategies, community based practices, community cohesion, cultural preservation, healing-centered, public housing, relocation, trauma-informed

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1101 Development of Vapor Absorption Refrigeration System for Mini-Bus Car’s Air Conditioning: A Two-Fluid Model

Authors: Yoftahe Nigussie

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This research explores the implementation of a vapor absorption refrigeration system (VARS) in mini-bus cars to enhance air conditioning efficiency. The conventional vapor compression refrigeration system (VCRS) in vehicles relies on mechanical work from the engine, leading to increased fuel consumption. The proposed VARS aims to utilize waste heat and exhaust gas from the internal combustion engine to cool the mini-bus cabin, thereby reducing fuel consumption and atmospheric pollution. The project involves two models: Model 1, a two-fluid vapor absorption system (VAS), and Model 2, a three-fluid VAS. Model 1 uses ammonia (NH₃) and water (H₂O) as refrigerants, where water absorbs ammonia rapidly, producing a cooling effect. The absorption cycle operates on the principle that absorbing ammonia in water decreases vapor pressure. The ammonia-water solution undergoes cycles of desorption, condensation, expansion, and absorption, facilitated by a generator, condenser, expansion valve, and absorber. The objectives of this research include reducing atmospheric pollution, minimizing air conditioning maintenance costs, lowering capital costs, enhancing fuel economy, and eliminating the need for a compressor. The comparison between vapor absorption and compression systems reveals advantages such as smoother operation, fewer moving parts, and the ability to work at lower evaporator pressures without affecting the Coefficient of Performance (COP). The proposed VARS demonstrates potential benefits for mini-bus air conditioning systems, providing a sustainable and energy-efficient alternative. By utilizing waste heat and exhaust gas, this system contributes to environmental preservation while addressing economic considerations for vehicle owners. Further research and development in this area could lead to the widespread adoption of vapor absorption technology in automotive air conditioning systems.

Keywords: room, zone, space, thermal resistance

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1100 A Multi-criteria Decision Method For The Recruitment Of Academic Personnel Based On The Analytical Hierarchy Process And The Delphi Method In A Neutrosophic Environment (Full Text)

Authors: Antonios Paraskevas, Michael Madas

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For a university to maintain its international competitiveness in education, it is essential to recruit qualitative academic staff as it constitutes its most valuable asset. This selection demonstrates a significant role in achieving strategic objectives, particularly by emphasizing a firm commitment to exceptional student experience and innovative teaching and learning practices of high quality. In this vein, the appropriate selection of academic staff establishes a very important factor of competitiveness, efficiency and reputation of an academic institute. Within this framework, our work demonstrates a comprehensive methodological concept that emphasizes on the multi-criteria nature of the problem and on how decision makers could utilize our approach in order to proceed to the appropriate judgment. The conceptual framework introduced in this paper is built upon a hybrid neutrosophic method based on the Neutrosophic Analytical Hierarchy Process (N-AHP), which uses the theory of neutrosophy sets and is considered suitable in terms of significant degree of ambiguity and indeterminacy observed in decision-making process. To this end, our framework extends the N-AHP by incorporating the Neutrosophic Delphi Method (N-DM). By applying the N-DM, we can take into consideration the importance of each decision-maker and their preferences per evaluation criterion. To the best of our knowledge, the proposed model is the first which applies Neutrosophic Delphi Method in the selection of academic staff. As a case study, it was decided to use our method to a real problem of academic personnel selection, having as main goal to enhance the algorithm proposed in previous scholars’ work, and thus taking care of the inherit ineffectiveness which becomes apparent in traditional multi-criteria decision-making methods when dealing with situations alike. As a further result, we prove that our method demonstrates greater applicability and reliability when compared to other decision models.

Keywords: analytical hierarchy process, delphi method, multi-criteria decision maiking method, neutrosophic set theory, personnel recruitment

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1099 Risk of Fractures at Different Anatomic Sites in Patients with Irritable Bowel Syndrome: A Nationwide Population-Based Cohort Study

Authors: Herng-Sheng Lee, Chi-Yi Chen, Wan-Ting Huang, Li-Jen Chang, Solomon Chih-Cheng Chen, Hsin-Yi Yang

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A variety of gastrointestinal disorders, such as Crohn’s disease, ulcerative colitis, and coeliac disease, are recognized as risk factors for osteoporosis and osteoporotic fractures. One recent study suggests that individuals with irritable bowel syndrome (IBS) might also be at increased risk of osteoporosis and osteoporotic fractures. Up to now, the association between IBS and the risk of fractures at different anatomic sites occurrences is not completely clear. We conducted a population-based cohort analysis to investigate the fracture risk of IBS in comparison with non-IBS group. We identified 29,505 adults aged ≥ 20 years with newly diagnosed IBS using the Taiwan National Health Insurance Research Database in 2000-2012. A comparison group was constructed of patients without IBS who were matched according to gender and age. The occurrence of fracture was monitored until the end of 2013. We analyzed the risk of fracture events to occur in IBS by using Cox proportional hazards regression models. Patients with IBS had a higher incidence of osteoporotic fractures compared with non-IBS group (12.34 versus 9.45 per 1,000 person-years) and an increased risk of osteoporotic fractures (adjusted hazard ratio [aHR] = 1.27, 95 % confidence interval [CI] = 1.20 – 1.35). Site specific analysis showed that the IBS group had a higher risk of fractures for spine, forearm, hip and hand than did the non-IBS group. With further stratification for gender and age, a higher aHR value for osteoporotic fractures in IBS group was seen across all age groups in males, but seen in elderly females. In addition, female, elderly, low income, hypertension, coronary artery disease, cerebrovascular disease, and depressive disorders as independent osteoporotic fracture risk factors in IBS patients. The IBS is considered as a risk factor for osteoporotic fractures, particularly in female individuals and fracture sites located at the spine, forearm, hip and hand.

Keywords: irritable bowel syndrome, fracture, gender difference, longitudinal health insurance database, public health

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1098 Exploring Socio-Economic Barriers of Green Entrepreneurship in Iran and Their Interactions Using Interpretive Structural Modeling

Authors: Younis Jabarzadeh, Rahim Sarvari, Negar Ahmadi Alghalandis

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Entrepreneurship at both individual and organizational level is one of the most driving forces in economic development and leads to growth and competition, job generation and social development. Especially in developing countries, the role of entrepreneurship in economic and social prosperity is more emphasized. But the effect of global economic development on the environment is undeniable, especially in negative ways, and there is a need to rethink current business models and the way entrepreneurs act to introduce new businesses to address and embed environmental issues in order to achieve sustainable development. In this paper, green or sustainable entrepreneurship is addressed in Iran to identify challenges and barriers entrepreneurs in the economic and social sectors face in developing green business solutions. Sustainable or green entrepreneurship has been gaining interest among scholars in recent years and addressing its challenges and barriers need much more attention to fill the gap in the literature and facilitate the way those entrepreneurs are pursuing. This research comprised of two main phases: qualitative and quantitative. At qualitative phase, after a thorough literature review, fuzzy Delphi method is utilized to verify those challenges and barriers by gathering a panel of experts and surveying them. In this phase, several other contextually related factors were added to the list of identified barriers and challenges mentioned in the literature. Then, at the quantitative phase, Interpretive Structural Modeling is applied to construct a network of interactions among those barriers identified at the previous phase. Again, a panel of subject matter experts comprised of academic and industry experts was surveyed. The results of this study can be used by policymakers in both the public and industry sector, to introduce more systematic solutions to eliminate those barriers and help entrepreneurs overcome challenges of sustainable entrepreneurship. It also contributes to the literature as the first research in this type which deals with the barriers of sustainable entrepreneurship and explores their interaction.

Keywords: green entrepreneurship, barriers, fuzzy Delphi method, interpretive structural modeling

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1097 Europe's War on Refugees: The Increased Need for International Protection and Promotion of Migrant Rights

Authors: Rai Friedman

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The recent migrant crisis has revealed an unmet demand for increased international protection and promotion of migrant rights. Europe has found itself at the centre of the migration crisis, being the recipient to the largest number of asylum-seekers since the conclusion of the second World War. Rather than impart a unified humanitarian lens of offering legal protections, the Schengen territory is devising new, preventative measures to confront the influx of asylum-seekers. This paper will focus on the refugee crisis in Europe as it relates to the Central Mediterranean route. To do so, it will outline the increased need for international protection for migrant rights through analyzing historic human rights treaties and conventions; the formation of the current composition of the Schengen area; the evolutionary changes in policies and legal landscapes throughout Europe and the Central Mediterranean route; the vernacular transformation surrounding refugees, migrants, and asylum-seekers; and expose the gaps in international protection. It will also discuss Europe’s critical position, both geographically and conceptually, critiquing the notion of European victimization. Lastly, it will discuss the increased harm of preventative border measures and argue for tangible sustainability solutions through economic programming models in highly vulnerable countries. To do so, this paper will observe a case study in Algeria that has conceded to an economic programming model for forced migrants. In 2017 amid worker shortages, Algeria announced it would grant African migrants’ legal status to become agriculturalists and construction workers. Algeria is one of the few countries along the Central Mediterranean route that has adopted a law to govern foreign nationals’ conditions of entry, stay and circulation. Thereafter, it will provide recommendations for solutions for forced migration along the Central Mediterranean route and advocate for strengthened protections under international law.

Keywords: refugees, migrants, human rights, middle east, Africa, mediterranean, international humanitarian law, policy

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1096 Tourism and Sustainability Example Projects in the EU

Authors: Renee Yi-Mond Yuan

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The fast development of tourism industries around the world, has largely contributed to many cities, and countries economical and social progress. Past year Taiwan in particular was ranked among one of fastest raise growth country. Thanks to the prominent importance of this phenomenon; seasonal mobility or multipurpose trips have reached more than 1 Billion tourists crossing International borders and more than 4 billion intramural travelers that have nourished the economy and employment in the service sector in most attractive regions, representing about one tenth of World GDP amount, including trade, research, cultural or journalistic purposes. Then the increased activities are giving pressure to the consumption of energy, water, resources, and Greenhouse Gas emissions. The further concentration of tourists in most beautiful sites of the World with consistent supply and reduced pollutions and means for waste control and risks management are challenging the preservation and protection of the natural original environment, including species and their ecosystems, ethnics and their cultures or languages, protection of inherited landscapes and monuments for the future generations to come. In this article, few projects will be analyzed, methods and directions in the EU sustainable development scheme giving way to economical and social activities and preserve rural areas and remote countryside as well as smarter cities development. EU ETS forecasting escalation in the next few decades for road and air, and will reconsider investments and reliance on Biobased alternatives that may turn out solutions and contributions to sustain popularization of tourism development. Study of Examples of Stakeholders practices and Governments efforts, consumer’s attitude to bring new forms of more responsible holidays models: ecotourism, eco-certification, partnerships, investment in technologies and facilities, and possibly create greener perceptions and less impacting demands for the longer term through association, organizations and awards.

Keywords: tourism, sustainability, protection, risks management, change in rural/urban environment

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1095 Prevalence, Antimicrobial Susceptibility Pattern and Associated Risk Factors for Salmonella Species and Escherichia coli from Raw Meat at Butchery Houses in Mekelle, Tigray, Ethiopia

Authors: Haftay Abraha Tadesse, Atsebaha Gebrekidan Kahsay, Mahumd Abdulkader

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Background: Salmonella species and Escherichia coli are important foodborne pathogens affecting humans and animals. They are among the most important causes of infection that are associated with the consumption of contaminated food. This study was aimed to determine the prevalence, antimicrobial susceptibility patterns and associated risk factors for Salmonella species and E. coli in raw meat from butchery houses of Mekelle, Northern Ethiopia. Methodology: A cross-sectional study was conducted from January to September 2019. Socio-demographic data and risk factors were collected using a predesigned questionnaire. Meat samples were collected aseptically from the butchery houses and transported using icebox to Mekelle University, College of Veterinary Sciences for the isolation and identification of Salmonella species and E. coli, Antimicrobial susceptibility patterns were determined using Kirby disc diffusion method. Data obtained were cleaned and entered into Statistical Package for the Social Sciences version 22 and logistic regression models with odds ratio were calculated. P-value < 0.05 was considered as statistically significant. Results: A total of 153 out of 384 (39.8%) of the meat specimens were found to be contaminated. The contamination of Salmonella species and E. coli were 15.6% (n=60) and 20.8%) (n=80), respectively. Mixed contamination (Salmonella species and E. coli) was observed in 13 (3.4 %) of the analyzed. Poor washing hands regularly (AOR = 8.37; 95% CI: 2.75-25.50) and not using gloves during meat handling (AOR=11. 28; 95% CI: (4.69 27.10) were associated with an overall bacterial contamination.About 95.5% of the tested isolates were sensitive to chloramphenicol and norfloxacin while the resistance of amoxyclav_amoxicillin and erythromycin were both isolated bacteria species. The overall multidrug resistance pattern for Salmonella and E. coli were 51.4% (n=19) and 31.8% (14), respectively. Conclusion: Of the 153 (153/384) contaminated raw meat, 60 (15.6%) and 80 (20.8%) were contaminated by Salmonella species and E. coli, respectively. Poor hand washing practice and not using glove during meat handling showed significant association with bacterial contamination. Multidrug-resistant showed in Salmonella species and E. coli were 19 (51.4%) and 14 (31.8%), respectively.

Keywords: antimicrobial susceptibility test, butchery houses, e. coli, salmonella species

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1094 Copula Autoregressive Methodology for Simulation of Solar Irradiance and Air Temperature Time Series for Solar Energy Forecasting

Authors: Andres F. Ramirez, Carlos F. Valencia

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The increasing interest in renewable energies strategies application and the path for diminishing the use of carbon related energy sources have encouraged the development of novel strategies for integration of solar energy into the electricity network. A correct inclusion of the fluctuating energy output of a photovoltaic (PV) energy system into an electric grid requires improvements in the forecasting and simulation methodologies for solar energy potential, and the understanding not only of the mean value of the series but the associated underlying stochastic process. We present a methodology for synthetic generation of solar irradiance (shortwave flux) and air temperature bivariate time series based on copula functions to represent the cross-dependence and temporal structure of the data. We explore the advantages of using this nonlinear time series method over traditional approaches that use a transformation of the data to normal distributions as an intermediate step. The use of copulas gives flexibility to represent the serial variability of the real data on the simulation and allows having more control on the desired properties of the data. We use discrete zero mass density distributions to assess the nature of solar irradiance, alongside vector generalized linear models for the bivariate time series time dependent distributions. We found that the copula autoregressive methodology used, including the zero mass characteristics of the solar irradiance time series, generates a significant improvement over state of the art strategies. These results will help to better understand the fluctuating nature of solar energy forecasting, the underlying stochastic process, and quantify the potential of a photovoltaic (PV) energy generating system integration into a country electricity network. Experimental analysis and real data application substantiate the usage and convenience of the proposed methodology to forecast solar irradiance time series and solar energy across northern hemisphere, southern hemisphere, and equatorial zones.

Keywords: copula autoregressive, solar irradiance forecasting, solar energy forecasting, time series generation

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1093 Interrogation of the Role of First Year Student Experiences in Student Success at a University of Technology in South Africa

Authors: Livingstone Makondo

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This ongoing research explores what could be the components of a comprehensive First-Year Student Experience (FYSE) at the Durban University of Technology (DUT) and the preferred implementation modalities. In light of the Siyaphumelela project, this interrogation is premised on the need to glean data for the institution that could be used to ascertain the role of FYSE towards enhancing student success. The research proceeds by examining prevalent models from other South African Universities and beyond in its quest to get at pragmatic comprehensive FYSE programme for DUT. As DUT is a student centered institution and amidst the ever shrinking economy, this research would aid higher education practitioners to ascertain if the hard earned finances are being channelled to a worthy academic venture. This research seeks to get inputs from a) students who participated in FYSE and are now in second and third years at DUT b) students who are currently participating in FYSE c) former and present Tutors d) departmental coordinators e) academics and support staff working with the participating students. This exploratory approach is preferred since 2010 DUT has grappled with how to implement an integrated institution-wide FYSE. This findings of this research could provide the much-needed data to ascertain if the current FYSE package is pivotal towards attainment of DUT Strategic Focus Area 1: Building sustainable student communities of living and learning. The ideal is to have DUT FYSE programme become an institution-wide programme that lays the foundation for consolidated and focused student development programmes for subsequent undergraduate and postgraduate levels of study. Also, armed with data from this research, DUT could develop the capacity and systems to ensure that all students get diverse on-time support to enhance their retention and academic success in their tertiary studies. In essence, the preferred FYSE curriculum woven around DUT graduate attributes should contribute towards the reduction in the first-year students’ dropout rates and subsequently in undergraduate studies. Therefore, this on-going research will feed into Siyaphumelela project and would help position 2018-2020 FYSE initiatives at DUT.

Keywords: challenges, comprehensive, dropout, transition

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1092 Comparison of Data Reduction Algorithms for Image-Based Point Cloud Derived Digital Terrain Models

Authors: M. Uysal, M. Yilmaz, I. Tiryakioğlu

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Digital Terrain Model (DTM) is a digital numerical representation of the Earth's surface. DTMs have been applied to a diverse field of tasks, such as urban planning, military, glacier mapping, disaster management. In the expression of the Earth' surface as a mathematical model, an infinite number of point measurements are needed. Because of the impossibility of this case, the points at regular intervals are measured to characterize the Earth's surface and DTM of the Earth is generated. Hitherto, the classical measurement techniques and photogrammetry method have widespread use in the construction of DTM. At present, RADAR, LiDAR, and stereo satellite images are also used for the construction of DTM. In recent years, especially because of its superiorities, Airborne Light Detection and Ranging (LiDAR) has an increased use in DTM applications. A 3D point cloud is created with LiDAR technology by obtaining numerous point data. However recently, by the development in image mapping methods, the use of unmanned aerial vehicles (UAV) for photogrammetric data acquisition has increased DTM generation from image-based point cloud. The accuracy of the DTM depends on various factors such as data collection method, the distribution of elevation points, the point density, properties of the surface and interpolation methods. In this study, the random data reduction method is compared for DTMs generated from image based point cloud data. The original image based point cloud data set (100%) is reduced to a series of subsets by using random algorithm, representing the 75, 50, 25 and 5% of the original image based point cloud data set. Over the ANS campus of Afyon Kocatepe University as the test area, DTM constructed from the original image based point cloud data set is compared with DTMs interpolated from reduced data sets by Kriging interpolation method. The results show that the random data reduction method can be used to reduce the image based point cloud datasets to 50% density level while still maintaining the quality of DTM.

Keywords: DTM, Unmanned Aerial Vehicle (UAV), uniform, random, kriging

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1091 A Framework for an Automated Decision Support System for Selecting Safety-Conscious Contractors

Authors: Rawan A. Abdelrazeq, Ahmed M. Khalafallah, Nabil A. Kartam

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Selection of competent contractors for construction projects is usually accomplished through competitive bidding or negotiated contracting in which the contract bid price is the basic criterion for selection. The evaluation of contractor’s safety performance is still not a typical criterion in the selection process, despite the existence of various safety prequalification procedures. There is a critical need for practical and automated systems that enable owners and decision makers to evaluate contractor safety performance, among other important contractor selection criteria. These systems should ultimately favor safety-conscious contractors to be selected by the virtue of their past good safety records and current safety programs. This paper presents an exploratory sequential mixed-methods approach to develop a framework for an automated decision support system that evaluates contractor safety performance based on a multitude of indicators and metrics that have been identified through a comprehensive review of construction safety research, and a survey distributed to domain experts. The framework is developed in three phases: (1) determining the indicators that depict contractor current and past safety performance; (2) soliciting input from construction safety experts regarding the identified indicators, their metrics, and relative significance; and (3) designing a decision support system using relational database models to integrate the identified indicators and metrics into a system that assesses and rates the safety performance of contractors. The proposed automated system is expected to hold several advantages including: (1) reducing the likelihood of selecting contractors with poor safety records; (2) enhancing the odds of completing the project safely; and (3) encouraging contractors to exert more efforts to improve their safety performance and practices in order to increase their bid winning opportunities which can lead to significant safety improvements in the construction industry. This should prove useful to decision makers and researchers, alike, and should help improve the safety record of the construction industry.

Keywords: construction safety, contractor selection, decision support system, relational database

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1090 Tobacco Taxation and the Heterogeneity of Smokers' Responses to Price Increases

Authors: Simone Tedeschi, Francesco Crespi, Paolo Liberati, Massimo Paradiso, Antonio Sciala

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This paper aims at contributing to the understanding of smokers’ responses to cigarette prices increases with a focus on heterogeneity, both across individuals and price levels. To do this, a stated preference quasi-experimental design grounded in a random utility framework is proposed to evaluate the effect on smokers’ utility of the price level and variation, along with social conditioning and health impact perception. The analysis is based on individual-level data drawn from a unique survey gathering very detailed information on Italian smokers’ habits. In particular, qualitative information on the individual reactions triggered by changes in prices of different magnitude and composition are exploited. The main findings stemming from the analysis are the following; the average price elasticity of cigarette consumption is comparable with previous estimates for advanced economies (-.32). However, the decomposition of this result across five latent-classes of smokers, reveals extreme heterogeneity in terms of price responsiveness, implying a potential price elasticity that ranges between 0.05 to almost 1. Such heterogeneity is in part explained by observable characteristics such as age, income, gender, education as well as (current and lagged) smoking intensity. Moreover, price responsiveness is far from being independent from the size of the prospected price increase. Finally, by comparing even and uneven price variations, it is shown that uniform across-brand price increases are able to limit the scope of product substitutions and downgrade. Estimated price-response heterogeneity has significant implications for tax policy. Among them, first, it provides evidence and a rationale for why the aggregate price elasticity is likely to follow a strictly increasing pattern as a function of the experienced price variation. This information is crucial for forecasting the effect of a given tax-driven price change on tax revenue. Second, it provides some guidance on how to design excise tax reforms to balance public health and revenue goals.

Keywords: smoking behaviour, preference heterogeneity, price responsiveness, cigarette taxation, random utility models

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1089 Advances in Mathematical Sciences: Unveiling the Power of Data Analytics

Authors: Zahid Ullah, Atlas Khan

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The rapid advancements in data collection, storage, and processing capabilities have led to an explosion of data in various domains. In this era of big data, mathematical sciences play a crucial role in uncovering valuable insights and driving informed decision-making through data analytics. The purpose of this abstract is to present the latest advances in mathematical sciences and their application in harnessing the power of data analytics. This abstract highlights the interdisciplinary nature of data analytics, showcasing how mathematics intersects with statistics, computer science, and other related fields to develop cutting-edge methodologies. It explores key mathematical techniques such as optimization, mathematical modeling, network analysis, and computational algorithms that underpin effective data analysis and interpretation. The abstract emphasizes the role of mathematical sciences in addressing real-world challenges across different sectors, including finance, healthcare, engineering, social sciences, and beyond. It showcases how mathematical models and statistical methods extract meaningful insights from complex datasets, facilitating evidence-based decision-making and driving innovation. Furthermore, the abstract emphasizes the importance of collaboration and knowledge exchange among researchers, practitioners, and industry professionals. It recognizes the value of interdisciplinary collaborations and the need to bridge the gap between academia and industry to ensure the practical application of mathematical advancements in data analytics. The abstract highlights the significance of ongoing research in mathematical sciences and its impact on data analytics. It emphasizes the need for continued exploration and innovation in mathematical methodologies to tackle emerging challenges in the era of big data and digital transformation. In summary, this abstract sheds light on the advances in mathematical sciences and their pivotal role in unveiling the power of data analytics. It calls for interdisciplinary collaboration, knowledge exchange, and ongoing research to further unlock the potential of mathematical methodologies in addressing complex problems and driving data-driven decision-making in various domains.

Keywords: mathematical sciences, data analytics, advances, unveiling

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1088 Organisational Change: The Impact on Employees and Organisational Development

Authors: Maureen Royce, Joshi Jariwala, Sally Kah

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Change is inevitable, but the change process is progressive. Organisational change is the process in which an organisation changes strategies, operational methods, systems, culture, and structure to affect something different in the organisation. This process can be continuous or developed over a period and driven by internal and external factors. Organisational change is essential if organisations are to survive in dynamic and uncertain environments. However, evidence from research shows that many change initiatives fail, leading to severe consequences for organisations and their resources. The complex models of third sector organisations, i.e., social enterprise, compounds the levels of change in these organisations. Interestingly, innovation is associated with a change in social enterprises due to the hybridity of product and service development. Furthermore, the creation of social intervention has offered a new process and outcomes to the lifecycle of change. Therefore, different forms of organisational innovation are developed, i.e., total, evolutionary, expansionary, and developmental, which affect the interventions of social enterprises. This raises both theoretical and business concerns on how the competing hybrid nature of social enterprises change, how change is managed, and the impact on these organisations. These perspectives present critical questions for further investigation. In this study, we investigate the impact of organisational change on employees and organisational development at DaDaFest –a disability arts organisation with a social focus based in Liverpool. The three main objectives are to explore the drivers of change and the implementation process; to examine the impact of organisational change on employees and; to identify barriers to organisation change and development. To address the preceding research objectives, qualitative research design is adopted using semi-structured interviews. Data is analysed using a six-step thematic analysis framework, which enables the study to develop themes depicting the impact of change on employees and organisational development. This study presents theoretical and practical contributions for academics and practitioners. The knowledge contributions encapsulate the evolution of change and the change cycle in a social enterprise. However, practical implications provide critical insights into the change management process and the impact of change on employees and organisational development.

Keywords: organisational change, change management, organisational change system, social enterprise

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1087 Transmission Dynamics of Lumpy Skin Disease in Ethiopia

Authors: Wassie Molla, Klaas Frankena, Mart De Jong

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Lumpy skin disease (LSD) is a severe viral disease of cattle, which often occurs in epidemic form. It is caused by lumpy skin disease virus of the genus capripoxvirus of family poxviridae. Mathematical models play important role in the study of infectious diseases epidemiology. They help to explain the dynamics and understand the transmission of an infectious disease within a population. Understanding the transmission dynamics of lumpy skin disease between animals is important for the implementation of effective prevention and control measures against the disease. This study was carried out in central and north-western part of Ethiopia with the objectives to understand LSD outbreak dynamics, quantify the transmission between animals and herds, and estimate the disease reproduction ratio in dominantly crop-livestock mixed and commercial herd types. Field observation and follow-up study were undertaken, and the transmission parameters were estimated based on a SIR epidemic model in which individuals are susceptible (S), infected and infectious (I), and recovered and immune or dead (R) using the final size and generalized linear model methods. The result showed that a higher morbidity was recorded in infected crop-livestock (24.1%) mixed production system herds than infected commercial production (17.5%) system herds whereas mortality was higher in intensive (4.0%) than crop-livestock (1.5%) system and the differences were statistically significant. The transmission rate among animals and between herds were 0.75 and 0.68 per week, respectively in dominantly crop-livestock production system. The transmission study undertaken in dominantly crop-livestock production system highlighted the presence of statistically significant seasonal difference in LSD transmission among animals. The reproduction numbers of LSD in dominantly crop-livestock production system were 1.06 among animals and 1.28 between herds whereas it varies from 1.03 to 1.31 among animals in commercial production system. Though the R estimated for LSD in different production systems at different localities is greater than 1, its magnitude is low implying that the disease can be easily controlled by implementing the appropriate control measures.

Keywords: commercial, crop-livestock, Ethiopia, LSD, reproduction number, transmission

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1086 Epistemological and Ethical Dimensions of Current Concepts of Human Resilience in the Neurosciences

Authors: Norbert W. Paul

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Since a number of years, scientific interest in human resilience is rapidly increasing especially in psychology and more recently and highly visible in neurobiological research. Concepts of resilience are regularly discussed in the light of liminal experiences and existential challenges in human life. Resilience research is providing both, explanatory models and strategies to promote or foster human resilience. Surprisingly, these approaches attracted little attention so far in philosophy in general and in ethics in particular. This is even more astonishing given the fact that the neurosciences as such have been and still are of major interest to philosophy and ethics and even brought about the specialized field of neuroethics, which, however, is not concerned with concepts of resilience, so far. As a result of the little attention given to the topic of resilience, the whole concept has to date been a philosophically under-theorized. This abstinence of ethics and philosophy in resilience research is lamentable because resilience as a concept as well as resilience interventions based on neurobiological findings do undoubtedly pose philosophical, social and ethical questions. In this paper, we will argue that particular notions of resilience are crossing the sometimes fine line between maintaining a person’s mental health despite the impact of severe psychological or physical adverse events and ethically more debatable discourses of enhancement. While we neither argue for or against enhancement nor re-interpret resilience research and interventions by subsuming them strategies of psychological and/or neuro-enhancement, we encourage those who see social or ethical problems with enhancement technologies should also take a closer look on resilience and the related neurobiological concepts. We will proceed in three steps. In our first step, we will describe the concept of resilience in general and its neurobiological study in particular. Here, we will point out some important differences in the way ‘resilience’ is conceptualized and how neurobiological research understands resilience. In what follows we will try to show that a one-sided concept of resilience – as it is often presented in neurobiological research on resilience – does pose social and ethical problems. Secondly, we will identify and explore the social and ethical challenges of (neurobiological) enhancement. In the last and final step of this paper, we will argue that a one-sided reading of resilience can be understood as latent form of enhancement in transition and poses ethical questions similar to those discussed in relation to other approaches to the biomedical enhancement of humans.

Keywords: resilience, neurosciences, epistemology, bioethics

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1085 Climate Change Adaptation: Methodologies and Tools to Define Resilience Scenarios for Existing Buildings in Mediterranean Urban Areas

Authors: Francesca Nicolosi, Teresa Cosola

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Climate changes in Mediterranean areas, such as the increase of average seasonal temperatures, the urban heat island phenomenon, the intensification of solar radiation and the extreme weather threats, cause disruption events, so that climate adaptation has become a pressing issue. Due to the strategic role that the built heritage holds in terms of environmental impact and energy waste and its potentiality, it is necessary to assess the vulnerability and the adaptive capacity of the existing building to climate change, in order to define different mitigation scenarios. The aim of this research work is to define an optimized and integrated methodology for the assessment of resilience levels and adaptation scenarios for existing buildings in Mediterranean urban areas. Moreover, the study of resilience indicators allows us to define building environmental and energy performance in order to identify the design and technological solutions for the improvement of the building and its urban area potentialities. The methodology identifies step-by-step different phases, starting from the detailed study of characteristic elements of urban system: climatic, natural, human, typological and functional components are analyzed in their critical factors and their potential. Through the individuation of the main perturbing factors and the vulnerability degree of the system to the risks linked to climate change, it is possible to define mitigation and adaptation scenarios. They can be different, according to the typological, functional and constructive features of the analyzed system, divided into categories of intervention, and characterized by different analysis levels (from the single building to the urban area). The use of software simulations allows obtaining information on the overall behavior of the building and the urban system, to generate predictive models in the medium and long-term environmental and energy retrofit and to make a comparative study of the mitigation scenarios identified. The studied methodology is validated on a case study.

Keywords: climate impact mitigation, energy efficiency, existing building heritage, resilience

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1084 An Investigation into the Crystallization Tendency/Kinetics of Amorphous Active Pharmaceutical Ingredients: A Case Study with Dipyridamole and Cinnarizine

Authors: Shrawan Baghel, Helen Cathcart, Biall J. O'Reilly

Abstract:

Amorphous drug formulations have great potential to enhance solubility and thus bioavailability of BCS class II drugs. However, the higher free energy and molecular mobility of the amorphous form lowers the activation energy barrier for crystallization and thermodynamically drives it towards the crystalline state which makes them unstable. Accurate determination of the crystallization tendency/kinetics is the key to the successful design and development of such systems. In this study, dipyridamole (DPM) and cinnarizine (CNZ) has been selected as model compounds. Thermodynamic fragility (m_T) is measured from the heat capacity change at the glass transition temperature (Tg) whereas dynamic fragility (m_D) is evaluated using methods based on extrapolation of configurational entropy to zero 〖(m〗_(D_CE )), and heating rate dependence of Tg 〖(m〗_(D_Tg)). The mean relaxation time of amorphous drugs was calculated from Vogel-Tammann-Fulcher (VTF) equation. Furthermore, the correlation between fragility and glass forming ability (GFA) of model drugs has been established and the relevance of these parameters to crystallization of amorphous drugs is also assessed. Moreover, the crystallization kinetics of model drugs under isothermal conditions has been studied using Johnson-Mehl-Avrami (JMA) approach to determine the Avrami constant ‘n’ which provides an insight into the mechanism of crystallization. To further probe into the crystallization mechanism, the non-isothermal crystallization kinetics of model systems was also analysed by statistically fitting the crystallization data to 15 different kinetic models and the relevance of model-free kinetic approach has been established. In addition, the crystallization mechanism for DPM and CNZ at each extent of transformation has been predicted. The calculated fragility, glass forming ability (GFA) and crystallization kinetics is found to be in good correlation with the stability prediction of amorphous solid dispersions. Thus, this research work involves a multidisciplinary approach to establish fragility, GFA and crystallization kinetics as stability predictors for amorphous drug formulations.

Keywords: amorphous, fragility, glass forming ability, molecular mobility, mean relaxation time, crystallization kinetics, stability

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1083 Research on the Ecological Impact Evaluation Index System of Transportation Construction Projects

Authors: Yu Chen, Xiaoguang Yang, Lin Lin

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Traffic engineering construction is an important infrastructure for economic and social development. In the process of construction and operation, the ability to make a correct evaluation of the project's environmental impact appears to be crucial to the rational operation of existing transportation projects, the correct development of transportation engineering construction and the adoption of corresponding measures to scientifically carry out environmental protection work. Most of the existing research work on ecological and environmental impact assessment is limited to individual aspects of the environment and less to the overall evaluation of the environmental system; in terms of research conclusions, there are more qualitative analyses from the technical and policy levels, and there is a lack of quantitative research results and quantitative and operable evaluation models. In this paper, a comprehensive analysis of the ecological and environmental impacts of transportation construction projects is conducted, and factors such as the accessibility of data and the reliability of calculation results are comprehensively considered to extract indicators that can reflect the essence and characteristics. The qualitative evaluation indicators were screened using the expert review method, the qualitative indicators were measured using the fuzzy statistics method, the quantitative indicators were screened using the principal component analysis method, and the quantitative indicators were measured by both literature search and calculation. An environmental impact evaluation index system with the general objective layer, sub-objective layer and indicator layer was established, dividing the environmental impact of the transportation construction project into two periods: the construction period and the operation period. On the basis of the evaluation index system, the index weights are determined using the hierarchical analysis method, and the individual indicators to be evaluated are dimensionless, eliminating the influence of the original background and meaning of the indicators. Finally, the thesis uses the above research results, combined with the actual engineering practice, to verify the correctness and operability of the evaluation method.

Keywords: transportation construction projects, ecological and environmental impact, analysis and evaluation, indicator evaluation system

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1082 Mapping the Pain Trajectory of Breast Cancer Survivors: Results from a Retrospective Chart Review

Authors: Wilfred Elliam

Abstract:

Background: Pain is a prevalent and debilitating symptom among breast cancer patients, impacting their quality of life and overall well-being. The experience of pain in this population is multifaceted, influenced by a combination of disease-related factors, treatment side effects, and individual characteristics. Despite advancements in cancer treatment and pain management, many breast cancer patients continue to suffer from chronic pain, which can persist long after the completion of treatment. Understanding the progression of pain in breast cancer patients over time and identifying its correlates is crucial for effective pain management and supportive care strategies. The purpose of this research is to understand the patterns and progression of pain experienced by breast cancer survivors over time. Methods: Data were collected from breast cancer patients at Hartford Hospital at four time points: baseline, 3, 6 and 12 weeks. Key variables measured include pain, body mass index (BMI), fatigue, musculoskeletal pain, sleep disturbance, and demographic variables (age, employment status, cancer stage, and ethnicity). Binomial generalized linear mixed models were used to examine changes in pain and symptoms over time. Results: A total of 100 breast cancer patients aged  18 years old were included in the analysis. We found that the effect of time on pain (p = 0.024), musculoskeletal pain (p= <0.001), fatigue (p= <0.001), and sleep disturbance (p-value = 0.013) were statistically significant with pain progression in breast cancer patients. Patients using aromatase inhibitors have worse fatigue (<0.05) and musculoskeletal pain (<0.001) compared to patients with Tamoxifen. Patients who are obese (<0.001) and overweight (<0.001) are more likely to report pain compared to patients with normal weight. Conclusion: This study revealed the complex interplay between various factors such as time, pain, sleep disturbance in breast cancer patient. Specifically, pain, musculoskeletal pain, sleep disturbance, fatigue exhibited significant changes across the measured time points, indicating a dynamic pain progression in these patients. The findings provide a foundation for future research and targeted interventions aimed at improving pain in breast cancer patient outcomes.

Keywords: breast cancer, chronic pain, pain management, quality of life

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1081 Exploring Regularity Results in the Context of Extremely Degenerate Elliptic Equations

Authors: Zahid Ullah, Atlas Khan

Abstract:

This research endeavors to explore the regularity properties associated with a specific class of equations, namely extremely degenerate elliptic equations. These equations hold significance in understanding complex physical systems like porous media flow, with applications spanning various branches of mathematics. The focus is on unraveling and analyzing regularity results to gain insights into the smoothness of solutions for these highly degenerate equations. Elliptic equations, fundamental in expressing and understanding diverse physical phenomena through partial differential equations (PDEs), are particularly adept at modeling steady-state and equilibrium behaviors. However, within the realm of elliptic equations, the subset of extremely degenerate cases presents a level of complexity that challenges traditional analytical methods, necessitating a deeper exploration of mathematical theory. While elliptic equations are celebrated for their versatility in capturing smooth and continuous behaviors across different disciplines, the introduction of degeneracy adds a layer of intricacy. Extremely degenerate elliptic equations are characterized by coefficients approaching singular behavior, posing non-trivial challenges in establishing classical solutions. Still, the exploration of extremely degenerate cases remains uncharted territory, requiring a profound understanding of mathematical structures and their implications. The motivation behind this research lies in addressing gaps in the current understanding of regularity properties within solutions to extremely degenerate elliptic equations. The study of extreme degeneracy is prompted by its prevalence in real-world applications, where physical phenomena often exhibit characteristics defying conventional mathematical modeling. Whether examining porous media flow or highly anisotropic materials, comprehending the regularity of solutions becomes crucial. Through this research, the aim is to contribute not only to the theoretical foundations of mathematics but also to the practical applicability of mathematical models in diverse scientific fields.

Keywords: elliptic equations, extremely degenerate, regularity results, partial differential equations, mathematical modeling, porous media flow

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1080 Computational Assistance of the Research, Using Dynamic Vector Logistics of Processes for Critical Infrastructure Subjects Continuity

Authors: Urbánek Jiří J., Krahulec Josef, Urbánek Jiří F., Johanidesová Jitka

Abstract:

These Computational assistance for the research and modelling of critical infrastructure subjects continuity deal with this paper. It enables us the using of prevailing operation system MS Office (SmartArt...) for mathematical models, using DYVELOP (Dynamic Vector Logistics of Processes) method. It serves for crisis situations investigation and modelling within the organizations of critical infrastructure. In the first part of the paper, it will be introduced entities, operators and actors of DYVELOP method. It uses just three operators of Boolean algebra and four types of the entities: the Environments, the Process Systems, the Cases and the Controlling. The Process Systems (PrS) have five “brothers”: Management PrS, Transformation PrS, Logistic PrS, Event PrS and Operation PrS. The Cases have three “sisters”: Process Cell Case, Use Case and Activity Case. They all need for the controlling of their functions special Ctrl actors, except ENV – it can do without Ctrl. Model´s maps are named the Blazons and they are able mathematically - graphically express the relationships among entities, actors and processes. In the second part of this paper, the rich blazons of DYVELOP method will be used for the discovering and modelling of the cycling cases and their phases. The blazons need live PowerPoint presentation for better comprehension of this paper mission. The crisis management of energetic crisis infrastructure organization is obliged to use the cycles for successful coping of crisis situations. Several times cycling of these cases is a necessary condition for the encompassment of the both the emergency event and the mitigation of organization´s damages. Uninterrupted and continuous cycling process bring for crisis management fruitfulness and it is a good indicator and controlling actor of organizational continuity and its sustainable development advanced possibilities. The research reliable rules are derived for the safety and reliable continuity of energetic critical infrastructure organization in the crisis situation.

Keywords: blazons, computational assistance, DYVELOP method, critical infrastructure

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1079 Ill-Posed Inverse Problems in Molecular Imaging

Authors: Ranadhir Roy

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Inverse problems arise in medical (molecular) imaging. These problems are characterized by large in three dimensions, and by the diffusion equation which models the physical phenomena within the media. The inverse problems are posed as a nonlinear optimization where the unknown parameters are found by minimizing the difference between the predicted data and the measured data. To obtain a unique and stable solution to an ill-posed inverse problem, a priori information must be used. Mathematical conditions to obtain stable solutions are established in Tikhonov’s regularization method, where the a priori information is introduced via a stabilizing functional, which may be designed to incorporate some relevant information of an inverse problem. Effective determination of the Tikhonov regularization parameter requires knowledge of the true solution, or in the case of optical imaging, the true image. Yet, in, clinically-based imaging, true image is not known. To alleviate these difficulties we have applied the penalty/modified barrier function (PMBF) method instead of Tikhonov regularization technique to make the inverse problems well-posed. Unlike the Tikhonov regularization method, the constrained optimization technique, which is based on simple bounds of the optical parameter properties of the tissue, can easily be implemented in the PMBF method. Imposing the constraints on the optical properties of the tissue explicitly restricts solution sets and can restore uniqueness. Like the Tikhonov regularization method, the PMBF method limits the size of the condition number of the Hessian matrix of the given objective function. The accuracy and the rapid convergence of the PMBF method require a good initial guess of the Lagrange multipliers. To obtain the initial guess of the multipliers, we use a least square unconstrained minimization problem. Three-dimensional images of fluorescence absorption coefficients and lifetimes were reconstructed from contact and noncontact experimentally measured data.

Keywords: constrained minimization, ill-conditioned inverse problems, Tikhonov regularization method, penalty modified barrier function method

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1078 Pathologies in the Left Atrium Reproduced Using a Low-Order Synergistic Numerical Model of the Cardiovascular System

Authors: Nicholas Pearce, Eun-jin Kim

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Pathologies of the cardiovascular (CV) system remain a serious and deadly health problem for human society. Computational modelling provides a relatively accessible tool for diagnosis, treatment, and research into CV disorders. However, numerical models of the CV system have largely focused on the function of the ventricles, frequently overlooking the behaviour of the atria. Furthermore, in the study of the pressure-volume relationship of the heart, which is a key diagnosis of cardiac vascular pathologies, previous works often evoke popular yet questionable time-varying elastance (TVE) method that imposes the pressure-volume relationship instead of calculating it consistently. Despite the convenience of the TVE method, there have been various indications of its limitations and the need for checking its validity in different scenarios. A model of the combined left ventricle (LV) and left atrium (LA) is presented, which consistently considers various feedback mechanisms in the heart without having to use the TVE method. Specifically, a synergistic model of the left ventricle is extended and modified to include the function of the LA. The synergy of the original model is preserved by modelling the electro-mechanical and chemical functions of the micro-scale myofiber for the LA and integrating it with the microscale and macro-organ-scale heart dynamics of the left ventricle and CV circulation. The atrioventricular node function is included and forms the conduction pathway for electrical signals between the atria and ventricle. The model reproduces the essential features of LA behaviour, such as the two-phase pressure-volume relationship and the classic figure of eight pressure-volume loops. Using this model, disorders in the internal cardiac electrical signalling are investigated by recreating the mechano-electric feedback (MEF), which is impossible where the time-varying elastance method is used. The effects of AV node block and slow conduction are then investigated in the presence of an atrial arrhythmia. It is found that electrical disorders and arrhythmia in the LA degrade the CV system by reducing the cardiac output, power, and heart rate.

Keywords: cardiovascular system, left atrium, numerical model, MEF

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1077 Targeting Mre11 Nuclease Overcomes Platinum Resistance and Induces Synthetic Lethality in Platinum Sensitive XRCC1 Deficient Epithelial Ovarian Cancers

Authors: Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan

Abstract:

Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have comprehensively evaluated Mre11 in epithelial ovarian cancers. In clinical cohort that received platinum- based chemotherapy (n=331), Mre11 protein overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p=0.002). In the ovarian cancer genome atlas (TCGA) cohort (n=498), Mre11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with Mre11 mRNA levels (p<0.0001). Altered Mre11 levels was linked with genome wide alterations that can influence platinum sensitivity. At the transcriptomic level (n=1259), Mre11 overexpression was associated with poor PFS (p=0.003). ROC analysis showed an area under the curve (AUC) of 0.642 for response to platinum-based chemotherapy. Pre-clinically, Mre11 depletion by gene knock down or blockade by small molecule inhibitor (Mirin) reversed platinum resistance in ovarian cancer cells and in 3D spheroid models. Importantly, Mre11 inhibition was synthetically lethal in platinum sensitive XRCC1 deficient ovarian cancer cells and 3D-spheroids. Selective cytotoxicity was associated with DNA double strand break (DSB) accumulation, S-phase cell cycle arrest and increased apoptosis. We conclude that pharmaceutical development of Mre11 inhibitors is a viable clinical strategy for platinum sensitization and synthetic lethality in ovarian cancer.

Keywords: MRE11; XRCC1, ovarian cancer, platinum sensitization, synthetic lethality

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1076 A Review of Benefit-Risk Assessment over the Product Lifecycle

Authors: M. Miljkovic, A. Urakpo, M. Simic-Koumoutsaris

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Benefit-risk assessment (BRA) is a valuable tool that takes place in multiple stages during a medicine's lifecycle, and this assessment can be conducted in a variety of ways. The aim was to summarize current BRA methods used during approval decisions and in post-approval settings and to see possible future directions. Relevant reviews, recommendations, and guidelines published in medical literature and through regulatory agencies over the past five years have been examined. BRA implies the review of two dimensions: the dimension of benefits (determined mainly by the therapeutic efficacy) and the dimension of risks (comprises the safety profile of a drug). Regulators, industry, and academia have developed various approaches, ranging from descriptive textual (qualitative) to decision-analytic (quantitative) models, to facilitate the BRA of medicines during the product lifecycle (from Phase I trials, to authorization procedure, post-marketing surveillance and health technology assessment for inclusion in public formularies). These approaches can be classified into the following categories: stepwise structured approaches (frameworks); measures for benefits and risks that are usually endpoint specific (metrics), simulation techniques and meta-analysis (estimation techniques), and utility survey techniques to elicit stakeholders’ preferences (utilities). All these approaches share the following two common goals: to assist this analysis and to improve the communication of decisions, but each is subject to its own specific strengths and limitations. Before using any method, its utility, complexity, the extent to which it is established, and the ease of results interpretation should be considered. Despite widespread and long-time use, BRA is subject to debate, suffers from a number of limitations, and currently is still under development. The use of formal, systematic structured approaches to BRA for regulatory decision-making and quantitative methods to support BRA during the product lifecycle is a standard practice in medicine that is subject to continuous improvement and modernization, not only in methodology but also in cooperation between organizations.

Keywords: benefit-risk assessment, benefit-risk profile, product lifecycle, quantitative methods, structured approaches

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1075 Application of Response Surface Methodology in Optimizing Chitosan-Argan Nutshell Beads for Radioactive Wastewater Treatment

Authors: F. F. Zahra, E. G. Touria, Y. Samia, M. Ahmed, H. Hasna, B. M. Latifa

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The presence of radioactive contaminants in wastewater poses a significant environmental and health risk, necessitating effective treatment solutions. This study investigates the optimization of chitosan-Argan nutshell beads for the removal of radioactive elements from wastewater, utilizing Response Surface Methodology (RSM) to enhance the treatment efficiency. Chitosan, known for its biocompatibility and adsorption properties, was combined with Argan nutshell powder to form composite beads. These beads were then evaluated for their capacity to remove radioactive contaminants from synthetic wastewater. The Box-Behnken design (BBD) under RSM was employed to analyze the influence of key operational parameters, including initial contaminant concentration, pH, bead dosage, and contact time, on the removal efficiency. Experimental results indicated that all tested parameters significantly affected the removal efficiency, with initial contaminant concentration and pH showing the most substantial impact. The optimized conditions, as determined by RSM, were found to be an initial contaminant concentration of 50 mg/L, a pH of 6, a bead dosage of 0.5 g/L, and a contact time of 120 minutes. Under these conditions, the removal efficiency reached up to 95%, demonstrating the potential of chitosan-Argan nutshell beads as a viable solution for radioactive wastewater treatment. Furthermore, the adsorption process was characterized by fitting the experimental data to various isotherm and kinetic models. The adsorption isotherms conformed well to the Langmuir model, indicating monolayer adsorption, while the kinetic data were best described by the pseudo-second-order model, suggesting chemisorption as the primary mechanism. This study highlights the efficacy of chitosan-Argan nutshell beads in removing radioactive contaminants from wastewater and underscores the importance of optimizing treatment parameters using RSM. The findings provide a foundation for developing cost-effective and environmentally friendly treatment technologies for radioactive wastewater.

Keywords: adsorption, argan nutshell, beads, chitosan, mechanism, optimization, radioactive wastewater, response surface methodology

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