Search results for: directed evolution
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2416

Search results for: directed evolution

766 Smart Campus Digital Twin: Basic Framework - Current State, Trends and Challenges

Authors: Enido Fabiano de Ramos, Ieda Kanashiro Makiya, Francisco I. Giocondo Cesar

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This study presents an analysis of the Digital Twin concept applied to the academic environment, focusing on the development of a Digital Twin Smart Campus Framework. Using bibliometric analysis methodologies and literature review, the research investigates the evolution and applications of the Digital Twin in educational contexts, comparing these findings with the advances of Industry 4.0. It was identified gaps in the existing literature and highlighted the need to adapt Digital Twin principles to meet the specific demands of a smart campus. By integrating Industry 4.0 concepts such as automation, Internet of Things, and real-time data analytics, we propose an innovative framework for the successful implementation of the Digital Twin in academic settings. The results of this study provide valuable insights for university campus managers, allowing for a better understanding of the potential applications of the Digital Twin for operations, security, and user experience optimization. In addition, our framework offers practical guidance for transitioning from a digital campus to a digital twin smart campus, promoting innovation and efficiency in the educational environment. This work contributes to the growing literature on Digital Twins and Industry 4.0, while offering a specific and tailored approach to transforming university campuses into smart and connected spaces, high demanded by Society 5.0 trends. It is hoped that this framework will serve as a basis for future research and practical implementations in the field of higher education and educational technology.

Keywords: smart campus, digital twin, industry 4.0, education trends, society 5.0

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765 Artificial Law: Legal AI Systems and the Need to Satisfy Principles of Justice, Equality and the Protection of Human Rights

Authors: Begum Koru, Isik Aybay, Demet Celik Ulusoy

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The discipline of law is quite complex and has its own terminology. Apart from written legal rules, there is also living law, which refers to legal practice. Basic legal rules aim at the happiness of individuals in social life and have different characteristics in different branches such as public or private law. On the other hand, law is a national phenomenon. The law of one nation and the legal system applied on the territory of another nation may be completely different. People who are experts in a particular field of law in one country may have insufficient expertise in the law of another country. Today, in addition to the local nature of law, international and even supranational law rules are applied in order to protect basic human values and ensure the protection of human rights around the world. Systems that offer algorithmic solutions to legal problems using artificial intelligence (AI) tools will perhaps serve to produce very meaningful results in terms of human rights. However, algorithms to be used should not be developed by only computer experts, but also need the contribution of people who are familiar with law, values, judicial decisions, and even the social and political culture of the society to which it will provide solutions. Otherwise, even if the algorithm works perfectly, it may not be compatible with the values of the society in which it is applied. The latest developments involving the use of AI techniques in legal systems indicate that artificial law will emerge as a new field in the discipline of law. More AI systems are already being applied in the field of law, with examples such as predicting judicial decisions, text summarization, decision support systems, and classification of documents. Algorithms for legal systems employing AI tools, especially in the field of prediction of judicial decisions and decision support systems, have the capacity to create automatic decisions instead of judges. When the judge is removed from this equation, artificial intelligence-made law created by an intelligent algorithm on its own emerges, whether the domain is national or international law. In this work, the aim is to make a general analysis of this new topic. Such an analysis needs both a literature survey and a perspective from computer experts' and lawyers' point of view. In some societies, the use of prediction or decision support systems may be useful to integrate international human rights safeguards. In this case, artificial law can serve to produce more comprehensive and human rights-protective results than written or living law. In non-democratic countries, it may even be thought that direct decisions and artificial intelligence-made law would be more protective instead of a decision "support" system. Since the values of law are directed towards "human happiness or well-being", it requires that the AI algorithms should always be capable of serving this purpose and based on the rule of law, the principle of justice and equality, and the protection of human rights.

Keywords: AI and law, artificial law, protection of human rights, AI tools for legal systems

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764 Characterizing Surface Machining-Induced Local Deformation Using Electron Backscatter Diffraction

Authors: Wenqian Zhang, Xuelin Wang, Yujin Hu, Siyang Wang

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The subsurface layer of a component plays a significant role in its service performance. Any surface mechanical process during fabrication can introduce a deformed layer near the surface, which can be related to the microstructure alteration and strain hardening, and affects the mechanical properties and corrosion resistance of the material. However, there exists a great difficulty in determining the subsurface deformation induced by surface machining. In this study, electron backscatter diffraction (EBSD) was used to study the deformed layer of surface milled 316 stainless steel. The microstructure change was displayed by the EBSD maps and characterized by misorientation variation. The results revealed that the surface milling resulted in heavily nonuniform deformations in the subsurface layer and even in individual grains. The direction of the predominant grain deformation was about 30-60 deg to the machined surface. Moreover, a local deformation rate (LDR) was proposed to quantitatively evaluate the local deformation degree. Both of the average and maximum LDRs were utilized to characterize the deformation trend along the depth direction. It was revealed that the LDR had a strong correlation with the development of grain and sub-grain boundaries. In this work, a scan step size of 1.2 μm was chosen for the EBSD measurement. A LDR higher than 18 deg/μm indicated a newly developed grain boundary, while a LDR ranged from 2.4 to 18 deg/μm implied the generation of a sub-grain boundary. And a lower LDR than 2.4 deg/μm could only introduce a slighter deformation and no sub-grain boundary was produced. According to the LDR analysis with the evolution of grain or sub grain boundaries, the deformed layer could be classified into four zones: grain broken layer, seriously deformed layer, slightly deformed layer and non-deformed layer.

Keywords: surface machining, EBSD, subsurface layer, local deformation

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763 Global Analysis of Modern Economic Sanctions

Authors: I. L. Yakushev

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Economic sanctions are an integral part of the foreign policy repertoire of States. Increasingly, States and international organizations are resorting to sanctions to address a variety of issues -from fighting corruption to preventing the use of nuclear weapons. Over time, the ways in which economic sanctions have been used have changed, especially over the past two decades. In the late 1990s, the recognition of the humanitarian harm of economic sanctions and the "War on Terrorism" after the events of September 11, 2001, led to serious changes in the structure and mechanisms of their application. Questions about how these coercive tools work, when they are applied, what consequences they have, and when they are successful are still being determined by research conducted in the second half of the 20th century. The conclusions drawn from past cases of sanctions may not be fully applicable to the current sanctions policy. In the second half of the 20th century, most cases of sanctions were related to the United States, and it covered restrictions on international trade. However, over the past two decades, the European Union, the United Nations, and China have also been the main initiators of sanctions. Modern sanctions include targeted and financial restrictions and are applied against individuals, organizations, and companies. Changing the senders, targets, stakeholders, and economic instruments used in the sanctions policy has serious implications for effectiveness and results. The regulatory and bureaucratic infrastructure necessary to implement and comply with modern economic sanctions has become more reliable. This evolution of sanctions has provided the scientific community with an opportunity to study new issues of coercion and return to the old ones. The economic sanctions research program should be developed to be relevant for understanding the application of modern sanctions and their consequences.

Keywords: global analysis, economic sanctions, targeted sanctions, foreign policy, domestic policy, United Nations, European Union, USA, economic pressure

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762 Flipped Classroom in a European Public Health Program: The Need for Students' Self-Directness

Authors: Nynke de Jong, Inge G. P. Duimel-Peeters

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The flipped classroom as an instructional strategy and a type of blended learning that reverses the traditional learning environment by delivering instructional content, off- and online, in- and outside the classroom, has been implemented in a 4-weeks module focusing on ageing in Europe at the Maastricht University. The main aim regarding the organization of this module was implementing flipped classroom-principles in order to create meaningful learning opportunities, while educational technologies are used to deliver content outside of the classroom. Technologies used in this module were an online interactive real time lecture from England, two interactive face-to-face lectures with visual supports, one group session including role plays and team-based learning meetings. The cohort of 2015-2016, using educational technologies, was compared with the cohort of 2014-2015 on module evaluation such as organization and instructiveness of the module, who studied the same content, although conforming the problem-based educational strategy, i.e. educational base of the Maastricht University. The cohort of 2015-2016 with its specific organization, was also more profound evaluated on outcomes as (1) experienced duration of the lecture by students, (2) experienced content of the lecture, (3) experienced the extent of the interaction and (4) format of lecturing. It was important to know how students reflected on duration and content taken into account their background knowledge so far, in order to distinguish between sufficient enough regarding prior knowledge and therefore challenging or not fitting into the course. For the evaluation, a structured online questionnaire was used, whereby above mentioned topics were asked for to evaluate by scoring them on a 4-point Likert scale. At the end, there was room for narrative feedback so that interviewees could express more in detail, if they wanted, what they experienced as good or not regarding the content of the module and its organization parts. Eventually, the response rate of the evaluation was lower than expected (54%), however, due to written feedback and exam scores, we dare to state that it gives a good and reliable overview that encourages to work further on it. Probably, the response rate may be explained by the fact that resit students were included as well, and that there maybe is too much evaluation as some time points in the program. However, overall students were excited about the organization and content of the module, but the level of self-directed behavior, necessary for this kind of educational strategy, was too low. They need to be more trained in self-directness, therefore the module will be simplified in 2016-2017 with more clear and fewer topics and extra guidance (step by step procedure). More specific information regarding the used technologies will be explained at the congress, as well as the outcomes (min and max rankings, mean and standard deviation).

Keywords: blended learning, flipped classroom, public health, self-directness

Procedia PDF Downloads 219
761 Rehabilitation Team after Brain Damages as Complex System Integrating Consciousness

Authors: Olga Maksakova

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

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

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760 A Study on the Effect of Cod to Sulphate Ratio on Performance of Lab Scale Upflow Anaerobic Sludge Blanket Reactor

Authors: Neeraj Sahu, Ahmad Saadiq

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Anaerobic sulphate reduction has the potential for being effective and economically viable over conventional treatment methods for the treatment of sulphate-rich wastewater. However, a major challenge in anaerobic sulphate reduction is the diversion of a fraction of organic carbon towards methane production and some minor problem such as odour problems, corrosion, and increase of effluent chemical oxygen demand. A high-rate anaerobic technology has encouraged researchers to extend its application to the treatment of complex wastewaters with relatively low cost and energy consumption compared to physicochemical methods. Therefore, the aim of this study was to investigate the effects of COD/SO₄²⁻ ratio on the performance of lab scale UASB reactor. A lab-scale upflow anaerobic sludge blanket (UASB) reactor was operated for 170 days. In which first 60 days, for successful start-up with acclimation under methanogenesis and sulphidogenesis at COD/SO₄²⁻ of 18 and were operated at COD/SO₄²⁻ ratios of 12, 8, 4 and 1 to evaluate the effects of the presence of sulfate on the reactor performance. The reactor achieved maximum COD removal efficiency and biogas evolution at the end of acclimation (control). This phase lasted 53 days with 89.5% efficiency. The biogas was 0.6 L/d at (OLR) of 1.0 kg COD/m³d when it was treating synthetic wastewater with effective volume of reactor as 2.8 L. When COD/SO₄²⁻ ratio changed from 12 to 1, slight decrease in COD removal efficiencies (76.8–87.4%) was observed, biogas production decreased from 0.58 to 0.32 L/d, while the sulfate removal efficiency increased from 42.5% to 72.7%.

Keywords: anaerobic, chemical oxygen demand, organic loading rate, sulphate, up-flow anaerobic sludge blanket reactor

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759 Molecular Electron Density Theory Study on the Mechanism and Selectivity of the 1,3 Dipolar Cycloaddition Reaction of N-Methyl-C-(2-Furyl) Nitrone with Activated Alkenes

Authors: Moulay Driss Mellaoui, Abdallah Imjjad, Rachid Boutiddar, Haydar Mohammad-Salim, Nivedita Acharjee, Hassan Bourzi, Souad El Issami, Khalid Abbiche, Hanane Zejli

Abstract:

We have investigated the underlying molecular processes involved in the [3+2] cycloaddition (32CA) reactions between N-methyl-C-(2-furyl) nitrone and three acetylene derivatives: 4b, 5b, and 6b. For this investigation, we utilized molecular electron density theory (MEDT) and density functional theory (DFT) methods at the B3LYP-D3/6 31G (d) computational level. These 32CA reactions, which exhibit a zwitterionic (zw-type) nature, proceed through a one-step mechanism with activation enthalpies ranging from 8.80 to 14.37 kcal mol−1 in acetonitrile and ethanol solvents. When the nitrone reacts with phenyl methyl propiolate (4b), two regioisomeric pathways lead to the formation of two products: P1,5-4b and P1,4-4b. On the other hand, when the nitrone reacts with dimethyl acetylene dicarboxylate (5b) and acetylene dicarboxylic acid (but-2-ynedioic acid) (6b), it results in the formation of a single product. Through topological analysis, we can categorize the nitrone as a zwitterionic three-atom component (TAC). Furthermore, the analysis of conceptual density functional theory (CDFT) indices classifies the 32CA reactions of the nitrone with 4b, 5b, and 6b as forward electron density flux (FEDF) reactions. The study of bond evolution theory (BET) reveals that the formation of new C-C and C-O covalent bonds does not initiate in the transition states, as the intermediate stages of these reactions display pseudoradical centers of the atoms already involved in bonding.

Keywords: 4-isoxazoline, DFT/B3LYP-D3, regioselectivity, cycloaddition reaction, MEDT, ELF

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758 Optimization of Smart Beta Allocation by Momentum Exposure

Authors: J. B. Frisch, D. Evandiloff, P. Martin, N. Ouizille, F. Pires

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Smart Beta strategies intend to be an asset management revolution with reference to classical cap-weighted indices. Indeed, these strategies allow a better control on portfolios risk factors and an optimized asset allocation by taking into account specific risks or wishes to generate alpha by outperforming indices called 'Beta'. Among many strategies independently used, this paper focuses on four of them: Minimum Variance Portfolio, Equal Risk Contribution Portfolio, Maximum Diversification Portfolio, and Equal-Weighted Portfolio. Their efficiency has been proven under constraints like momentum or market phenomenon, suggesting a reconsideration of cap-weighting.
 To further increase strategy return efficiency, it is proposed here to compare their strengths and weaknesses inside time intervals corresponding to specific identifiable market phases, in order to define adapted strategies depending on pre-specified situations. 
Results are presented as performance curves from different combinations compared to a benchmark. If a combination outperforms the applicable benchmark in well-defined actual market conditions, it will be preferred. It is mainly shown that such investment 'rules', based on both historical data and evolution of Smart Beta strategies, and implemented according to available specific market data, are providing very interesting optimal results with higher return performance and lower risk.
 Such combinations have not been fully exploited yet and justify present approach aimed at identifying relevant elements characterizing them.

Keywords: smart beta, minimum variance portfolio, equal risk contribution portfolio, maximum diversification portfolio, equal weighted portfolio, combinations

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757 Experimental Model of the Behaviour of Bolted Angles Connections with Stiffeners

Authors: Abdulkadir Cuneyt Aydin, Mahyar Maali, Mahmut Kılıç, Merve Sağıroğlu

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The moment-rotation curves of semi-rigid connections are the visual expressions of the actual behaviour discovered in beam-to-column connections experiments. This research was to determine the behaviour of the connection using full-scale experiments under statically loaded. The stiffeners which are typically attached to beams web or flanges to control local buckling and to increase shear capacity in a beam web are almost always used in modern designs. They must also provide sufficient moment of inertia to control out of plane deformations. This study was undertaken to analyse the influence of stiffeners in the angles and beams on the behaviour of the beam-to-column joints. In addition, the aim was to provide necessary data to improve the Eurocode 3. The main parameters observed are the evolution of the resistance, the stiffness, the rotation capacity, the ductility of a joint and the Energy Dissipation. Experimental tests show that the plastic flexural resistance and the energy dissipation increased when thickness of stiffener beam, thickness of stiffener angles were increased in the test specimens. And also, while stiffness of joints, the bending moment capacity and the maximum bending moment increased with the increasing thickness of stiffener beam, these values decreased with the increasing thickness of stiffener angles. So, it is observed that the beam stiffener of angles are important in improving resistance moment of beam-to-column semi-rigid joints.

Keywords: bolted angles connection, semi-rigid joints, ductility of a joint, angles and beams stiffeners

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756 Shifting Gender Roles: Exploring Settler Communities in Guam and Bali

Authors: Rochelle Alviz, Kirk Johnson

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This study explores the changing nature of gender roles in two traditional island societies. The research focuses particularly on the settler populations within each community (the Filipinos in Guam and the Javanese in Bali). The research seeks to understand the influence of both the forces of globalization and the dynamics of competing cultures on gender roles. To achieve this, a qualitative research design is used, employing in-depth interviews with individuals from both communities and field notes from participant observation. The study finds that globalization and competing cultural norms have influenced traditional gender roles and expectations in two primary areas of social life: the family and the economy. The importance of these two areas of social life to both communities has led to changes and adaptations in gender roles. In the family context, individuals reconcile their traditional gender roles from their country of origin with the dominant or indigenous gender roles of their new place of residence. In the economic context, the study finds that gender roles influence economic participation, including the types of jobs individuals pursue based on their gender roles. The results of the study provide valuable insights into the complexities and nuances of gender roles and the different factors that influence their evolution and adaptation over time. The research also highlights the influence of globalization on traditional societies and settler populations and the ways in which individuals navigate the competing cultural norms and expectations surrounding gender roles. The research contributes to a better understanding of the interplay between culture, globalization, and gender roles and the implications of these changes for individuals and communities.

Keywords: gender roles, culture, settler communities, family, economy, Guam, Bali, globalization

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755 The Impact of the Board of Directors’ Characteristics on Tax Aggressiveness in USA Companies

Authors: jihen ayadi sellami

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The rapid evolution of the global financial landscape has led to increased attention to corporate tax policies and the need to understand the factors that influence their tax behavior. In order to mitigate any residual loss for shareholders resulting from tax aggressiveness and resolve the agency problem, appropriate systems that separate the function of management from that of controlling are needed. In this context of growing concerns to limit aggressive corporate taxation practices through governance, this study discusses. Its aims is to examine the influence of six key characteristics of the board of directors (board size, diligence, CEO duality, presence of audit committees, gender diversity and independence of directors), given a governance mechanism, on the tax decisions of non-financial corporations in the United State. In fact, using a sample of 90 non-financial US firms from S&P 500 over a period of 4 years going from 2014 to 2017, the results based on a multivariate linear regression highlight significant associations between these characteristics and corporate tax policy. Notably, larger board, gender diversity, diligence and increased director independence appear to play an important role in reducing aggressive taxation. While duality has a positive and significant correlation with tax aggressiveness, that can be explained by the fact that the manager did properly exploit his specific position within the company. These findings contribute to a deeper understanding of how board characteristics can influence corporate tax management, providing avenues for more effective corporate governance and more responsible tax decision-making

Keywords: tax aggressiveness, board of directors, board size, CEO duality, audit committees, gender diversity, director independence, diligence, corporate governance, united states

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754 Detection of Trends and Break Points in Climatic Indices: The Case of Umbria Region in Italy

Authors: A. Flammini, R. Morbidelli, C. Saltalippi

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The increase of air surface temperature at global scale is a fact, with values around 0.85 ºC since the late nineteen century, as well as a significant change in main features of rainfall regime. Nevertheless, the detected climatic changes are not equally distributed all over the world, but exhibit specific characteristics in different regions. Therefore, studying the evolution of climatic indices in different geographical areas with a prefixed standard approach becomes very useful in order to analyze the existence of climatic trend and compare results. In this work, a methodology to investigate the climatic change and its effects on a wide set of climatic indices is proposed and applied at regional scale in the case study of a Mediterranean area, Umbria region in Italy. From data of the available temperature stations, nine temperature indices have been obtained and the existence of trends has been checked by applying the non-parametric Mann-Kendall test, while the non-parametric Pettitt test and the parametric Standard Normal Homogeneity Test (SNHT) have been applied to detect the presence of break points. In addition, aimed to characterize the rainfall regime, data from 11 rainfall stations have been used and a trend analysis has been performed on cumulative annual rainfall depth, daily rainfall, rainy days, and dry periods length. The results show a general increase in any temperature indices, even if with a trend pattern dependent of indices and stations, and a general decrease of cumulative annual rainfall and average daily rainfall, with a time rainfall distribution over the year different from the past.

Keywords: climatic change, temperature, rainfall regime, trend analysis

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753 Effects of Bariatric Surgery on Preventing the Progression of Diabetic Retinopathy

Authors: Yunzi Chen, James Laybourne, Sarah Steven, Peter Carey, David Steel, Maria Sandinha

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Introduction: Bariatric surgery is popular with the rising incidence of obesity. Its well-known benefits include significant and rapid glycaemic control. However, cases of paradoxical worsening in diabetic retinopathy (DR) despite improved glycaemic control have been reported. Purpose: clarification on the evolution of diabetic retinopathy after bariatric surgery. Method: retrospective study of 40 patients with Type 2 diabetes who underwent bariatric surgery in a UK specialist bariatric unit between 2009 and 2011. Pre-operative and post-operative visual acuity (VA), weight, HbA1c and annual DRSS screening results were analysed. Median follow up was 50 months. Results: No significant change in VA was found during the post-operative period. 85% of patients improved HbA1c post-operatively of which 53% achieved non-diabetic HbA1c of <6.1% - despite this, 2 patients developed new DR. First post-operative screening showed 80% of patients experienced no change, 8% improved but 13% of patients developed new DR (1 case with sight-threatening maculopathy). 80% of these cases persisted up to 24 months. The proportion of patients developing new or worse DR fluctuated over time, peaking at the 3rd annual screening with 26% (15% regressed, 56% stable). The probability of developing new or worse DR postoperatively was significantly associated with a high pre-operative HbA1c (>8%) and male gender. Conclusions: bariatric surgery does not guarantee long-term improvement or prevention of DR. Asymptomatic changes in DR occurred up to 5 years postoperatively. We therefore consider it prudent to continue screening in this cohort of patients.

Keywords: bariatric surgery, diabetic retinopathy, obesity, type 2 diabetes mellitus

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752 Spatial Distribution and Time Series Analysis of COVID-19 Pandemic in Italy: A Geospatial Perspective

Authors: Muhammad Farhan Ul Moazzam, Tamkeen Urooj Paracha, Ghani Rahman, Byung Gul Lee, Nasir Farid, Adnan Arshad

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The novel coronavirus pandemic disease (COVID-19) affected the whole globe, though there is a lack of clinical studies and its epidemiological features. But as per the observation, it has been seen that most of the COVID-19 infected patients show mild to moderate symptoms, and they get better without any medical assistance due to a better immune system to generate antibodies against the novel coronavirus. In this study, the active cases, serious cases, recovered cases, deaths and total confirmed cases had been analyzed using the geospatial inverse distance weightage technique (IDW) within the time span of 2nd March to 3rd June 2020. As of 3rd June, the total number of COVID-19 cases in Italy were 231,238, total deaths 33,310, serious cases 350, recovered cases 158,951, and active cases were 39,177, which has been reported by the Ministry of Health, Italy. March 2nd-June 3rd, 2020 a sum of 231,238 cases has been reported in Italy out of which 38.68% cases reported in the Lombardia region with a death rate of 18%, which is high from its national mortality rate followed by Emilia-Romagna (14.89% deaths), Piemonte (12.68% deaths), and Vento (10% deaths). As per the total cases in the region, the highest number of recoveries has been observed in Umbria (92.52%), followed by Basilicata (87%), Valle d'Aosta (86.85%), and Trento (84.54%). The COVID-19 evolution in Italy has been particularly found in the major urban area, i.e., Rome, Milan, Naples, Bologna, and Florence. Geospatial technology played a vital role in this pandemic by tracking infected patient, active cases, and recovered cases. Geospatial techniques are very important in terms of monitoring and planning to control the pandemic spread in the country.

Keywords: COVID-19, public health, geospatial analysis, IDW, Italy

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751 European Union Health Policy and the Response to COVID-19 Pandemic: Building a European Health Union

Authors: Aikaterini Tsalampouni

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The European Union has long been the most developed model of economic and political integration that has brought a common market, a common currency and a standardization of national policies in certain areas in consistent with EU values and principles. To this direction, there is a parallel process of social integration that effect public policy decisions of member states. Even though social policy, i.e. social protection and moreover healthcare policy, still remains in state's responsibility to develop, EU applies different mechanisms in order to influence health policy systems, since from a more federalist point of view, EU ought to expand its regulatory and legislative roles in as many policy areas as possible. Recently, the pandemic has become a turning point for health care provision and at the same time has also highlighted the need to strengthen the EU’s role in coordinating health care. This paper analyses the EU health policy in general, as well as the response to COVID-19 pandemic with an attempt to identify indications of interaction between EU policies and the promotion of sustainable and resilient health systems. More analytically, the paper investigates the EU binding legal instruments, non-binding legal instruments, monitoring and assessment instruments and instruments for co-financing concerning health care provision in member states and records the evolution of health policies before and during the COVID-19 pandemic. The paper concludes by articulating some remarks regarding the improvement of health policy in EU. Since the ability to deal with a pandemic depends on continuous and increased investment in health systems, the involvement of the EU can lead to a policy convergence, necessary for the resilience of the systems, maintaining at the same time, a strong health policy framework in Europe.

Keywords: EU health policy, EU response to COVID-19, European Health Union, health systems in Europe

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750 Preparation of Catalyst-Doped TiO2 Nanotubes by Single Step Anodization and Potential Shock

Authors: Hyeonseok Yoo, Kiseok Oh, Jinsub Choi

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Titanium oxide nanotubes have attracted great attention because of its photocatalytic activity and large surface area. For enhancing electrochemical properties, catalysts should be doped into the structure because titanium oxide nanotubes themselves have low electroconductivity and catalytic activity. It has been reported that Ru and Ir doped titanium oxide electrodes exhibit high efficiency and low overpotential in the oxygen evolution reaction (OER) for water splitting. In general, titanium oxide nanotubes with high aspect ratio cannot be easily doped by conventional complex methods. Herein, two types of facile routes, namely single step anodization and potential shock, for Ru doping into high aspect ratio titanium oxide nanotubes are introduced in detail. When single step anodization was carried out, stability of electrodes were increased. However, onset potential was shifted to anodic direction. On the other hand, when high potential shock voltage was applied, a large amount of ruthenium/ruthenium oxides were doped into titanium oxide nanotubes and thick barrier oxide layers were formed simultaneously. Regardless of doping routes, ruthenium/ ruthenium oxides were homogeneously doped into titanium oxide nanotubes. In spite of doping routes, doping in aqueous solution generally led to incorporate high amount of Ru in titanium oxide nanotubes, compared to that in non-aqueous solution. The amounts of doped catalyst were analyzed by X-ray photoelectron spectroscopy (XPS). The optimum condition for water splitting was investigated in terms of the amount of doped Ru and thickness of barrier oxide layer.

Keywords: doping, potential shock, single step anodization, titanium oxide nanotubes

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749 Power Asymmetry and Major Corporate Social Responsibility Projects in Mhondoro-Ngezi District, Zimbabwe

Authors: A. T. Muruviwa

Abstract:

Empirical studies of the current CSR agenda have been dominated by literature from the North at the expense of the nations from the South where most TNCs are located. Therefore, owing to the limitations of the current discourse that is dominated by Western ideas such as voluntarism, philanthropy, business case and economic gains, scholars have been calling for a new CSR agenda that is South-centred and addresses the needs of developing nations. The development theme has dominated in the recent literature as scholars concerned with the relationship between business and society have tried to understand its relationship with CSR. Despite a plethora of literature on the roles of corporations in local communities and the impact of CSR initiatives, there is lack of adequate empirical evidence to help us understand the nexus between CSR and development. For all the claims made about the positive and negative consequences of CSR, there is surprisingly little information about the outcomes it delivers. This study is a response to these claims made about the developmental aspect of CSR in developing countries. It offers some empirical bases for assessing the major CSR projects that have been fulfilled by a major mining company, Zimplats in Mhondoro-Ngezi Zimbabwe. The neo-liberal idea of capitalism and market dominations has empowered TNCs to stamp their authority in the developing countries. TNCs have made their mark in developing nations as they stamp their global private authority, rivalling or implicitly challenging the state in many functions. This dominance of corporate power raises great concerns over their tendencies of abuses in terms of environmental, social and human rights concerns as well as how to make them increasingly accountable. The hegemonic power of TNCs in the developing countries has had a tremendous impact on the overall CSR practices. While TNCs are key drivers of globalization they may be acting responsibly in their Global Northern home countries where there is a combination of legal mechanisms and the fear of civil society activism associated with corporate scandals. Using a triangulated approach in which both qualitative and quantitative methods were used the study found out that most CSR projects in Zimbabwe are dominated and directed by Zimplats because of the power it possesses. Most of the major CSR projects are beneficial to the mining company as they serve the business plans of the mining company. What was deduced from the study is that the infrastructural development initiatives by Zimplats confirm that CSR is a tool to advance business obligations. This shows that although proponents of CSR might claim that business has a mandate for social obligations to society, we need not to forget the dominant idea that the primary function of CSR is to enhance the firm’s profitability.

Keywords: hegemonic power, projects, reciprocity, stakeholders

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748 Anton Bruckner’s Requiem in Dm: The Reinterpretation of a Liturgical Genre in the Viennese Romantic Context

Authors: Sara Ramos Contioso

Abstract:

The premiere of Anton Bruckner's Requiem in Dm, in September 1849, represents a turning point in the composer's creative evolution. This Mass of the Dead, which was dedicated to the memory of his esteemed friend and mentor Franz Sailer, establishes the beginning of a new creative aesthetic in the composer´s production and links its liturgical development, which is contextualized in the monastery of St. Florian, to the use of a range of musicals possibilities that are projected by Bruckner on an orchestral texture with choir and organ. Set on a strict tridentine ritual model, this requiem exemplifies the religious aesthetics of a composer that is committed to the Catholic faith and that also links to its structure the reinterpretation of a religious model that, despite being romantic, shows a strong influence derived from the baroque or the Viennese Classicism language. Consequently, the study responds to the need to show the survival of the Requiem Mass within the romantic context of Vienna. Therefore, it draws on a detailed analysis of the score and the creative context of the composer with the intention of linking the work to the tradition of the genre and also specifying the stylistic particularities of its musical model within a variability of possibilities such as the contrasting precedents of Mozart, Haydn, Cherubini or Berlioz´s requiems. Tradition or modernity, liturgy or concert hall are aesthetic references that will condition the development of the Requiem Mass in the middle of the nineteenth century. In this context, this paper tries to recover Bruckner's Requiem in Dm as a musical model of the romantic ritual of deceased and as a stylistic reference of a creative composition that will condition the development of later liturgical works such as Liszt or DeLange (1868) ones.

Keywords: liturgy, religious symbolism, requiem, romanticism

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747 Reflecting Socio-Political Needs in Education Policy-Making: An Exploratory Study of Vietnam's Key Education Reforms (1945-2017)

Authors: Linh Tong

Abstract:

This paper aims to contribute to the understanding of key education reforms in Vietnam from 1945 to 2017, which reflects an evolution of socio-political needs of the Socialist Republic of Vietnam throughout this period. It explores the contextual conditions, motivations and ambitions influencing the formation of the education reforms in Vietnam. It also looks, from an applied practical perspective, at the influence of politics on education policy-making. The research methodology includes a content analysis of curriculum designs proposed by the Ministry of Education and Training, relevant resolutions and executive orders passed by the National Assembly and the Prime Minister, as well as interviews with experts and key stakeholders. The results point to a particular configuration of factors which have been inspiring the shape and substance of these reforms and which have most certainly influenced their implementation. This configuration evolves from the immediate needs to erase illiteracy and cultivate socialist economic model at the beginning of Vietnam’s independence in 1945-1975, to a renewed urge to adopt market-oriented economy in 1986 and cautiously communicate with the outside world until 2000s, and to currently a demonstrated desire to fully integrate into the global economy and tackle with rising concerns about national security (the South China Sea Dispute), environmental sustainability, construction of a knowledge economy, and a rule-of-law society. Overall, the paper attempts to map Vietnam’s socio-political needs with the changing sets of goals and expected outcomes in teaching and learning methodologies and practices as introduced in Vietnamese key education reforms.

Keywords: curriculum development, knowledge society, national security, politics of education policy-making, Vietnam's education reforms

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746 The Paleoenvironment and Paleoclimatological Variations during Aptian in North Central Tunisia

Authors: Houda Khaled, Frederic Boulvain, Fredj Chaabani

Abstract:

This paper focuses on the sedimentological and mineralogical studies of Aptian series outcrops in the Serdj and Bellouta Mountain situated in north-central Tunisia. In the Serdj Mountain, the Aptian series is about 590 meters thick and it is defined by tow formations corresponding respectively to the Sidi Hamada formation (Barremian-Gragasian) and the Serdj formation (Middle Gragasian-Late Clansaysian). This later is consisting of five limestones sequences separated by marly levels limestones associated to some siltstones bed. The Bellouta section is especially composed of carbonate rocks and it is attributed to the Middle Gragasian - Late Clansaysian. These sections are studied in detail regarding lithology, micropaleontology, microfacies, magnetic susceptibility and mineralogical composition in order to provide new insights into the paleoenvironmental evolution and paleoclimatological implications during Aptian. The following facies associations representing different ramp palaeoenvironments have been identified: mudstone-wackestone outer ramp facies; skeletal grainstone-packstone mid-ramp facies, packstone-grainstone inner-ramp facies which include a variety of organisms such as ooliths, rudists ostracods associated to athor bioclats. The coastal facies is especially defined by a mudstone -wackestone texture coastal rich with miliolidea and orbitolines. The magnetic susceptibility (Xin) of all samples was compared with the lithological and microfacies variation. The MS curves show that the high values are correlated with the distal facies and the low values are registred in the coastal environment. The X-ray diffractometer analysis show the presence of kaolinite and illite.

Keywords: Aptian, Serdj formation, mineralogy, petrography

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745 The Interventricular Septum as a Site for Implantation of Electrocardiac Devices - Clinical Implications of Topography and Variation in Position

Authors: Marcin Jakiel, Maria Kurek, Karolina Gutkowska, Sylwia Sanakiewicz, Dominika Stolarczyk, Jakub Batko, Rafał Jakiel, Mateusz K. Hołda

Abstract:

Proper imaging of the interventricular septum during endocavital lead implantation is essential for successful procedure. The interventricular septum is located oblique to the 3 main body planes and forms angles of 44.56° ± 7.81°, 45.44° ± 7.81°, 62.49° (IQR 58.84° - 68.39°) with the sagittal, frontal and transverse planes, respectively. The optimal left anterior oblique (LAO) projection is to have the septum aligned along the radiation beam and will be obtained for an angle of 53.24° ± 9,08°, while the best visualization of the septal surface in the right anterior oblique (RAO) projection is obtained by using an angle of 45.44° ± 7.81°. In addition, the RAO angle (p=0.003) and the septal slope to the transverse plane (p=0.002) are larger in the male group, but the LAO angle (p=0.003) and the dihedral angle that the septum forms with the sagittal plane (p=0.003) are smaller, compared to the female group. Analyzing the optimal RAO angle in cross-sections lying at the level of the connections of the septum with the free wall of the right ventricle from the front and back, we obtain slightly smaller angle values, i.e. 41.11° ± 8.51° and 43.94° ± 7.22°, respectively. As the septum is directed leftward in the apical region, the optimal RAO angle for this area decreases (16.49° ± 7,07°) and does not show significant differences between the male and female groups (p=0.23). Within the right ventricular apex, there is a cavity formed by the apical segment of the interventricular septum and the free wall of the right ventricle with a depth of 12.35mm (IQR 11.07mm - 13.51mm). The length of the septum measured in longitudinal section, containing 4 heart cavities, is 73.03mm ± 8.06mm. With the left ventricular septal wall formed by the interventricular septum in the apical region at a length of 10.06mm (IQR 8.86 - 11.07mm) already lies outside the right ventricle. Both mentioned lengths are significantly larger in the male group (p<0.001). For proper imaging of the septum from the right ventricular side, an oblique position of the visualization devices is necessary. Correct determination of the RAO and LAO angle during the procedure allows to improve the procedure performed, and possible modification of the visual field when moving in the anterior, posterior and apical directions of the septum will avoid complications. Overlooking the change in the direction of the interventricular septum in the apical region and a significant decrease in the RAO angle can result in implantation of the lead into the free wall of the right ventricle with less effective pacing and even complications such as wall perforation and cardiac tamponade. The demonstrated gender differences can also be helpful in setting the right projections. A necessary addition to the analysis will be a description of the area of the ventricular septum, which we are currently working on using autopsy material.

Keywords: anatomical variability, angle, electrocardiological procedure, intervetricular septum

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744 Effect of Iron Oxide Addition on the Solid-State Synthesis of Ye’Elimite

Authors: F. Z. Abir, M. Mesnaoui, Y. Abouliatim, L. Nibou, Y. El Hafiane, A. Smith

Abstract:

The cement industry has been taking significant steps for years to reduce its carbon footprint by opting for an eco-friendly alternative such as Calcium Sulfoaluminate Cements (CSA). These binders, compared to Ordinary Portland Cements (OPC), have two advantages: reduction of the CO2 emissions and energy-saving because the sintering temperature of CSA cements is between 1250 and 1350 °C, which means 100 to 200 °C less than OPC. The aim of this work is to study the impurities effect, such as iron oxide, on the formation of the ye'elimite phase, which represents the main phase of Calcium Sulfoaluminate Cements and the consequence on its hydration. Several elaborations and characterization techniques were used to study the structure and microstructure of ye'elimite, such as X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), thermal analysis, specific surface area measurement, and electrical conductivity of diluted solutions. This study details the protocol for the solid-state synthesis of ye'elimite containing increasing amounts of iron (general formula: Ca4Al(6-2x)Fe2xSO16 with x = 0.00 to 1.13). Ye'elimite is formed by solid-state reactions between Al2O3, CaO and CaSO4 and the maximum ye'elimite content is reached at a sintering temperature of 1300 °C. The presence of iron promotes the formation of cubic ye'elimite at the expense of the orthorhombic phase. The total incorporation of iron in ye'elimite structure is possible when x < 0.12. Beyond this content, the ferritic phase (CaO)2(Al2O3,Fe2O3) appears as a minor phase and develops two different morphologies during cooling: dendritic crystals and melt morphology. The formation of the ferrous liquid phase affects the evolution of grain size of the ye’elimite and calcium aluminates.

Keywords: calcium sulfoaluminate cement, ferritic phase, sintering, solid-state synthesis, ye’elimite

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743 Considering International/Local Peacebuilding Partnerships: The Stoplights Analysis System

Authors: Charles Davidson

Abstract:

This paper presents the Stoplight Analysis System of Partnering Organizations Readiness, offering a structured framework to evaluate conflict resolution collaboration feasibility, especially crucial in conflict areas, employing a colour-coded approach and specific assessment points, with implications for more informed decision-making and improved outcomes in peacebuilding initiatives. Derived from at total of 40 years of practical peacebuilding experience from the project’s two researchers as well as interviews of various other peacebuilding actors, this paper introduces the Stoplight Analysis System of Partnering Organizations Readiness, a comprehensive framework designed to facilitate effective collaboration in international/local peacebuilding partnerships by evaluating the readiness of both potential partner organisations and the location of the proposed project. ^The system employs a colour-coded approach, categorising potential partnerships into three distinct indicators: Red (no-go), Yellow (requires further research), and Green (promising, go ahead). Within each category, specific points are identified for assessment, guiding decision-makers in evaluating the feasibility and potential success of collaboration. The Red category signals significant barriers, prompting an immediate stoppage in the consideration of partnership. The Yellow category encourages deeper investigation to determine whether potential issues can be mitigated, while the Green category signifies organisations deemed ready for collaboration. This systematic and structured approach empowers decision-makers to make informed choices, enhancing the likelihood of successful and mutually beneficial partnerships. Methodologically, this paper utilised interviews from peacebuilders from around the globe, scholarly research of extant strategies, and a collaborative review of programming from the project’s two authors from their own time in the field. This method as a formalised model has been employed for the past two years across a litany of partnership considerations, and has been adjusted according to its field experimentation. This research holds significant importance in the field of conflict resolution as it provides a systematic and structured approach to peacebuilding partnership evaluation. In conflict-affected regions, where the dynamics are complex and challenging, the Stoplight Analysis System offers decision-makers a practical tool to assess the readiness of partnering organisations. This approach can enhance the efficiency of conflict resolution efforts by ensuring that resources are directed towards partnerships with a higher likelihood of success, ultimately contributing to more effective and sustainable peacebuilding outcomes.

Keywords: collaboration, conflict resolution, partnerships, peacebuilding

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742 Integrated Design in Additive Manufacturing Based on Design for Manufacturing

Authors: E. Asadollahi-Yazdi, J. Gardan, P. Lafon

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Nowadays, manufactures are encountered with production of different version of products due to quality, cost and time constraints. On the other hand, Additive Manufacturing (AM) as a production method based on CAD model disrupts the design and manufacturing cycle with new parameters. To consider these issues, the researchers utilized Design For Manufacturing (DFM) approach for AM but until now there is no integrated approach for design and manufacturing of product through the AM. So, this paper aims to provide a general methodology for managing the different production issues, as well as, support the interoperability with AM process and different Product Life Cycle Management tools. The problem is that the models of System Engineering which is used for managing complex systems cannot support the product evolution and its impact on the product life cycle. Therefore, it seems necessary to provide a general methodology for managing the product’s diversities which is created by using AM. This methodology must consider manufacture and assembly during product design as early as possible in the design stage. The latest approach of DFM, as a methodology to analyze the system comprehensively, integrates manufacturing constraints in the numerical model in upstream. So, DFM for AM is used to import the characteristics of AM into the design and manufacturing process of a hybrid product to manage the criteria coming from AM. Also, the research presents an integrated design method in order to take into account the knowledge of layers manufacturing technologies. For this purpose, the interface model based on the skin and skeleton concepts is provided, the usage and manufacturing skins are used to show the functional surface of the product. Also, the material flow and link between the skins are demonstrated by usage and manufacturing skeletons. Therefore, this integrated approach is a helpful methodology for designer and manufacturer in different decisions like material and process selection as well as, evaluation of product manufacturability.

Keywords: additive manufacturing, 3D printing, design for manufacturing, integrated design, interoperability

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741 Culture, Consumption, and Markets of Aesthetics: A10-Year Literature Review

Authors: Chin-Hsiang Chu

Abstract:

This article review the literature in the field among the marketing and aesthetics, the current market and customer-oriented product sales, and gradually from the practical functionality, transformed into the visual appearance of the concept note and the importance of marketing experience substance 'economic Aesthetics' trend. How to introduce the concept of aesthetic and differentiate products have become an important content of marketing management in for an organization in marketing.In previous studies,marketing aesthetic related researches are rare.Therefore, the purpose of this study to explore the connection between aesthetics and marketing of the market economy, and aggregated content through literature review, trying to find related research implications for the management of marketing aesthetics, market-oriented and customer value and development of the product. In this study, the problem statement and background, the development of the theory of evolution, as well as methods and results of discovery stage, literature review was conducted to explore. The results found: (1) Study of Aesthetics will help deepen the shopping environment and service environment commonly understood. (2) the perceived value of products imported aesthetic, consumer willingness to buy, and even premium products will be more attractive. (3) marketing personnel for general marketing management with a high degree of aesthetic identity. (4) management in marketing aesthetics connotation, aesthetic characteristics of five elements is greatly valued by the real-time, complex, specificity, attract sexual and richness. (5) allows consumers to experience through the process due to stimulate the senses, the mind and thinking with the corporate brand or have a deeper link. Results of this study can be used as business in a competitive market, new product development and design of the guide.

Keywords: marketing aesthetics, aesthetics economic, aesthetic, experiential marketing

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740 Outcomes in New-Onset Diabetic Foot Ulcers Stratified by Etiology

Authors: Pedro Gomes, Lia Ferreira, Sofia Garcia, Jaime Babulal, Luís Costa, Luís Castelo, José Muras, Isabel Gonçalves, Rui Carvalho

Abstract:

Introduction: Foot ulcers and their complications are an important cause of morbidity and mortality in diabetes. Objectives: The present study aims to evaluate the outcomes in terms of need for hospitalization, amputation, healing time and mortality in patients with new-onset diabetic foot ulcers in subgroups stratified by etiology. Methods: A retrospective study based on clinical assessment of patients presenting with new ulcers to a multidisciplinary diabetic foot consult during 2012. Outcomes were determined until September 2014, from hospital registers. Baseline clinical examination was done to classify ulcers as neuropathic, ischemic or neuroischemic. Results: 487 patients with new diabetic foot ulcers were observed; 36%, 15% and 49% of patients had neuropathic, ischemic and neuroischemic ulcers, respectively. For analysis, patients were classified as having predominantly neuropathic (36%) or ischemic foot (64%). The mean age was significantly higher in the group with ischemic foot (70±12 vs 63±12 years; p <0.001), as well as the duration of diabetes (18±10 vs 16 ± 10years, p <0.05). A history of previous amputation was also significantly higher in this group (24.7% vs 15.6%, p <0.05). The evolution of ischemic ulcers was significantly worse, with a greater need for hospitalization (27.2% vs 18%, p <0.05), amputation (11.5% vs 3.6% p <0.05) mainly major amputation (3% vs. 0%; p <0.001) and higher mean healing time (151 days vs 89 days, p <0.05). The mortality rate at 18 months, was also significantly higher in the ischemic foot group (7.3% vs 1.8%, p <0.05). Conclusions: All types of diabetic foot ulcers are associated with high morbidity and mortality, however, the presence of arterial disease confers a poor prognosis. Diabetic foot can be successfully treated only by the multidisciplinary team which can provide more comprehensive and integrated care.

Keywords: diabetes, foot ulcers, etiology, outcome

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739 Implementation of the Quality Management System and Development of Organizational Learning: Case of Three Small and Medium-Sized Enterprises in Morocco

Authors: Abdelghani Boudiaf

Abstract:

The profusion of studies relating to the concept of organizational learning shows the importance that has been given to this concept in the management sciences. A few years ago, companies leaned towards ISO 9001 certification; this requires the implementation of the quality management system (QMS). In order for this objective to be achieved, companies must have a set of skills, which pushes them to develop learning through continuous training. The results of empirical research have shown that implementation of the QMS in the company promotes the development of learning. It should also be noted that several types of learning are developed in this sense. Given the nature of skills development is normative in the context of the quality demarche, companies are obliged to qualify and improve the skills of their human resources. Continuous training is the keystone to develop the necessary learning. To carry out continuous training, companies need to be able to identify their real needs by developing training plans based on well-defined engineering. The training process goes obviously through several stages. Initially, training has a general aspect, that is to say, it focuses on topics and actions of a general nature. Subsequently, this is done in a more targeted and more precise way to accompany the evolution of the QMS and also to make the changes decided each time (change of working method, change of practices, change of objectives, change of mentality, etc.). To answer our problematic we opted for the method of qualitative research. It should be noted that the case study method crosses several data collection techniques to explain and understand a phenomenon. Three cases of companies were studied as part of this research work using different data collection techniques related to this method.

Keywords: changing mentalities, continuing training, organizational learning, quality management system, skills development

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738 Evaluation of National Research Motivation Evolution with Improved Social Influence Network Theory Model: A Case Study of Artificial Intelligence

Authors: Yating Yang, Xue Zhang, Chengli Zhao

Abstract:

In the increasingly interconnected global environment brought about by globalization, it is crucial for countries to timely grasp the development motivations in relevant research fields of other countries and seize development opportunities. Motivation, as the intrinsic driving force behind actions, is abstract in nature, making it difficult to directly measure and evaluate. Drawing on the ideas of social influence network theory, the research motivations of a country can be understood as the driving force behind the development of its science and technology sector, which is simultaneously influenced by both the country itself and other countries/regions. In response to this issue, this paper improves upon Friedkin's social influence network theory and applies it to motivation description, constructing a dynamic alliance network and hostile network centered around the United States and China, as well as a sensitivity matrix, to remotely assess the changes in national research motivations under the influence of international relations. Taking artificial intelligence as a case study, the research reveals that the motivations of most countries/regions are declining, gradually shifting from a neutral attitude to a negative one. The motivation of the United States is hardly influenced by other countries/regions and remains at a high level, while the motivation of China has been consistently increasing in recent years. By comparing the results with real data, it is found that this model can reflect, to some extent, the trends in national motivations.

Keywords: influence network theory, remote assessment, relation matrix, dynamic sensitivity matrix

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737 Novel EGFR Ectodomain Mutations and Resistance to Anti-EGFR and Radiation Therapy in H&N Cancer

Authors: Markus Bredel, Sindhu Nair, Hoa Q. Trummell, Rajani Rajbhandari, Christopher D. Willey, Lewis Z. Shi, Zhuo Zhang, William J. Placzek, James A. Bonner

Abstract:

Purpose: EGFR-targeted monoclonal antibodies (mAbs) provide clinical benefit in some patients with H&N squamous cell carcinoma (HNSCC), but others progress with minimal response. Missense mutations in the EGFR ectodomain (ECD) can be acquired under mAb therapy by mimicking the effect of large deletions on receptor untethering and activation. Little is known about the contribution of EGFR ECD mutations to EGFR activation and anti-EGFR response in HNSCC. Methods: We selected patient-derived HNSCC cells (UM-SCC-1) for resistance to mAb Cetuximab (CTX) by repeated, stepwise exposure to mimic what may occur clinically and identified two concurrent EGFR ECD mutations (UM-SCC-1R). We examined the competence of the mutants to bind EGF ligand or CTX. We assessed the potential impact of the mutations through visual analysis of space-filling models of the native sidechains in the original structures vs. their respective side-chain mutations. We performed CRISPR in combination with site-directed mutagenesis to test for the effect of the mutants on ligand-independent EGFR activation and sorting. We determined the effects on receptor internalization, endocytosis, downstream signaling, and radiation sensitivity. Results: UM-SCC-1R cells carried two non-synonymous missense mutations (G33S and N56K) mapping to domain I in or near the EGF binding pocket of the EGFR ECD. Structural modeling predicted that these mutants restrict the adoption of a tethered, inactive EGFR conformation while not permitting association of EGFR with the EGF ligand or CTX. Binding studies confirmed that the mutant, untethered receptor displayed a reduced affinity for both EGF and CTX but demonstrated sustained activation and presence at the cell surface with diminished internalization and sorting for endosomal degradation. Single and double-mutant models demonstrated that the G33S mutant is dominant over the N56K mutant in its effect on EGFR activation and EGF binding. CTX-resistant UM-SCC-1R cells demonstrated cross-resistance to mAb Panitumuab but, paradoxically, remained sensitive to the reversible receptor tyrosine kinase inhibitor Erlotinib. Conclusions: HNSCC cells can select for EGFR ECD mutations under EGFR mAb exposure that converge to trap the receptor in an open, constitutively activated state. These mutants impede the receptor’s competence to bind mAbs and EGF ligand and alter its endosomal trafficking, possibly explaining certain cases of clinical mAb and radiation resistance.

Keywords: head and neck cancer, EGFR mutation, resistance, cetuximab

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