Search results for: human resource
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 10167

Search results for: human resource

7707 The Role of Chennai NGOs in Combatting Human Trafficking

Authors: Nisha James, Shubha Ranganathan

Abstract:

Sex trafficking is a type of human trafficking involving prostitution of individuals for sexual exploitation. The stigma and social isolation they face in the society often makes it difficult for them to become rehabilitated from trafficking, due to which many of them continue in prostitution for years after being sex trafficked. Victims are subjected to violations of their fundamental human rights, deprived of basic medical facilities and undergo long-term abuse. This paper focuses on the role of Non-Governmental Organizations (NGOs) in the rescue and rehabilitation of victims of sex trafficking. Semi-structured interviews were conducted with 26 survivors of sex trafficking, five sex workers and 14 non-community staff members of a project running NGO in the city of Chennai in South India. Chennai has a number of NGOs that are involved in HIV/AIDS awareness and prevention programs. In many cases, rehabilitation of sex trafficking victims is also a mandate of these NGOs. This particular NGO was also involved in development activities towards the eradication of HIV/AIDS. For instance, they were engaged in inculcating safe sex practices among high-risk groups such as sex workers or in fighting for sex worker rights. The study found that the NGO’s role in combatting sex trafficking is overrun by the way it approaches these issue related to HIV/AIDS. Further, their activities are dependent solely on funding. Given that gradually, international funding for HIV/AIDS has slowly been withdrawn, there have been problems such as reduction in the salary of the project staff, the outreach workers and peer educators, many of whom were survivors of sex trafficking who have been able to survive on their wages instead of continuing in prostitution. Therefore, till date, the project funding has helped in making them aware of the health and social consequences of continuing in prostitution, and in supporting them socioeconomically, but the lack of funding may also lead the NGO workers into a state of unemployment, poverty and eventually into being re-trafficked. The study concludes by pointing to the need for disengaging anti-trafficking efforts from the HIV/AIDS related programs.

Keywords: non-governmental organization role, non-governmental organization staff, sex trafficking survivors, sex workers

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7706 The Need for a One Health and Welfare Approach to Industrial Animal Farming

Authors: Clinton Adas

Abstract:

Industrial animal farming contributes to numerous problems that humans face, and among these, antimicrobial resistance (AMR) has been identified by the World Health Organisation as a real possibility for the 21st Century. While numerous factors contribute to AMR, one of them is industrial animal farming and its effect on the food chain and environment. In 2017, livestock were given around 73% of all antibiotics worldwide to make them grow faster for profit purposes, to prevent illness caused by unhealthy living conditions, and to treat disease when it breaks out. Many of the antibiotics used provide little benefit to animals, and most are the same as those used by humans - including many deemed critical to human health that should be used sparingly. AMR contributes to millions of illnesses, and in 2019 was responsible for around 4.95 million deaths worldwide. It costs Europe around nine billion euros per year, while it costs the United States (US) around 20 billion dollars per year. While not a simple or quick solution, one way to begin to address the challenge of AMR and other harms from this type of farming is to focus on animal welfare as part of a One Health and Welfare approach, as better welfare requires less antibiotics usage, which may begin to break the cycle.

Keywords: animal and human welfare, industrial animal farming, antimicrobial resistance, one health and welfare, sustainable development goals

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7705 Endoscopic Depiction and Treatment Evaluation of Spirocerca lupi in Dogs

Authors: ELdessouky Sheta, Sayed Elzomor, Haithem Farghali, Kawkab A. Ahmed, Naglaa A. Abd Elkader

Abstract:

The present investigation has been dealt with Spirocerca (S.) lupi infested mongrel dogs. This parasitic disease is highly infective to human beings and carnivores. The diagnosis march has been comprised the lateral contrast thoracic radiographs, fecal examination, blood profile, endoscopic examination and histopathological sections of deep seated pinch biopsies. These infested dogs have been put under an adopted treatment with Ivermectin injection combined with oral prednisolone. The obtained results reveal an absence of the pessimistic recognitions particularly after 3 weeks from the onset of treatment. Endoscopically the presented esophageal nodules are marked out in the distal third of infested dogs' esophagus as masses assigned into the esophageal lumen and fundus of stomach. The endoscopic outlook of Spirocerca lupi lesions has been considered an integral procedure of the diagnostic march and for evaluation of treatment follow up. The diagnostic procedures and the recommended treatment are the vet's guidance to care for Spirocerca lupi in dogs, hoping in future to prevent this disease from being spread among human beings and other carnivores.

Keywords: endoscopy, esophagus, stomach spirocercosis, dogs

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7704 An Overview on Micro Irrigation-Accelerating Growth of Indian Agriculture

Authors: Rohit Lall

Abstract:

The adoption of Micro Irrigation (MI) technologies in India has helped in achieving higher cropping and irrigation intensity with significant savings on resource savings such as labour, fertilizer and improved crop yields. These technologies have received considerable attention from policymakers, growers and researchers over the years for its perceived ability to contribute towards agricultural productivity and economic growth with the well-being of the growers of the country. Keeping the pace with untapped theoretical potential to cover government had launched flagship programs/centre sector schemes with earmarked budget to capture the potential under these waters saving techniques envisaged under these technologies by way of providing financial assistance to the beneficiaries for adopting these technologies. Micro Irrigation technologies have been in the special attention of the policymakers over the years. India being an agrarian economy having engaged 75% of the population directly or indirectly having skilled, semi-skilled and entrepreneurs in the sector with focused attention and financial allocations from the government under these technologies in covering the untapped potential under Pradhan Mantri Krishi Sinchayee Yojana (PMKSY) 'Per Drop More Crop component.' During the year 2004, a Taskforce on Micro Irrigation was constituted to estimate the potential of these technologies in India which was estimated 69.5 million hectares by the Task Force Report on MI however only 10.49 million hectares have been achieved so far. Technology collaborations by leading manufacturing companies in overseas have proved to a stepping stone in technology advancement and product up gradation with increased efficiencies. Joint ventures by the leading MI companies have added huge business volumes which have not only accelerated the momentum of achieving the desired goal but in terms of area coverage but had also generated opportunities for the polymer manufacturers in the country. To provide products matching the global standards Bureau of Indian Standards have constituted a sectional technical committee under the Food and Agriculture Department (FAD)-17 to formulated/devise and revise standards pertaining to MI technologies. The research lobby has also contributed at large by developing in-situ analysis proving MI technologies a boon for farming community of the country with resource conservation of which water is of paramount importance. Thus, Micro Irrigation technologies have proved to be the key tool for feeding the grueling demand of food basket of the growing population besides maintaining soil health and have been contributing towards doubling of farmers’ income.

Keywords: task force on MI, standards, per drop more crop, doubling farmers’ income

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7703 Electroencephalography-Based Intention Recognition and Consensus Assessment during Emergency Response

Authors: Siyao Zhu, Yifang Xu

Abstract:

After natural and man-made disasters, robots can bypass the danger, expedite the search, and acquire unprecedented situational awareness to design rescue plans. The hands-free requirement from the first responders excludes the use of tedious manual control and operation. In unknown, unstructured, and obstructed environments, natural-language-based supervision is not amenable for first responders to formulate, and is difficult for robots to understand. Brain-computer interface is a promising option to overcome the limitations. This study aims to test the feasibility of using electroencephalography (EEG) signals to decode human intentions and detect the level of consensus on robot-provided information. EEG signals were classified using machine-learning and deep-learning methods to discriminate search intentions and agreement perceptions. The results show that the average classification accuracy for intention recognition and consensus assessment is 67% and 72%, respectively, proving the potential of incorporating recognizable users’ bioelectrical responses into advanced robot-assisted systems for emergency response.

Keywords: consensus assessment, electroencephalogram, emergency response, human-robot collaboration, intention recognition, search and rescue

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7702 Survey the Effects of Climate in Traditional and Modern Architecture of Iran

Authors: Yousefali Ziari, Hamidreza Joudaki

Abstract:

Humans have regularly been interacting with their environment, and have a close relation with their environment. House as a shelter which protects us against hot and cold weather and the other climatic occurrences in the environment has a close relation with climate. Before human could have access to the fossil fuels, preparing the comfort for the house was done by adjusting the building according to the climate conditions, and the help of natural resources. However after the man could access the fossil fuel, this way was forgotten, and caused much use of energy for heating & cooling. This research is trying to find some methods for designing suitable building that create comfort fitting with the zone by studying the climate condition of Arak city and as a result to find a way to reduce the use of energy and improving the design. So for the aim of this research we have used the statistics and information such as temperature, rain, wind and the approximate moisture from a period of 40 years from synoptic station of Arak. After specifying the climate of Arak by the use of effective temperature, Ulgi, Guni, Mahani and Ovenz indicator, we investigated the climate comfort conditions and the harmonious architecture with the climate and then some suggestion was given according to the climate situation of each month of the year and quality of human comfort according to this indicators.

Keywords: climate, architecture, traditional and modern architecture, comfort indicator, Arak city

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7701 Collaborative Environmental Management: A Case Study Research of Stakeholders' Collaboration in the Nigerian Oil-Producing Region

Authors: Favour Makuochukwu Orji, Yingkui Zhao

Abstract:

A myriad of environmental issues face the Nigerian industrial region, resulting from; oil and gas production, mining, manufacturing and domestic wastes. Amidst these, much effort has been directed by stakeholders in the Nigerian oil producing regions, because of the impacts of the region on the wider Nigerian economy. Research to date has suggested that collaborative environmental management could be an effective approach in managing environmental issues; but little attention has been given to the roles and practices of stakeholders in effecting a collaborative environmental management framework for the Nigerian oil-producing region. This paper produces a framework to expand and deepen knowledge relating to stakeholders aspects of collaborative roles in managing environmental issues in the Nigeria oil-producing region. The knowledge is derived from analysis of stakeholders’ practices – studied through multiple case studies using document analysis. Selected documents of key stakeholders – Nigerian government agencies, multi-national oil companies and host communities, were analyzed. Open and selective coding was employed manually during document analysis of data collected from the offices and websites of the stakeholders. The findings showed that the stakeholders have a range of roles, practices, interests, drivers and barriers regarding their collaborative roles in managing environmental issues. While they have interests for efficient resource use, compliance to standards, sharing of responsibilities, generating of new solutions, and shared objectives; there is evidence of major barriers which includes resource allocation, disjointed policy and regulation, ineffective monitoring, diverse socio- economic interests, lack of stakeholders’ commitment and limited knowledge sharing. However, host communities hold deep concerns over the collaborative roles of stakeholders for economic interests, particularly, where government agencies and multi-national oil companies are involved. With these barriers and concerns, a genuine stakeholders’ collaboration is found to be limited, and as a result, optimal environmental management practices and policies have not been successfully implemented in the Nigeria oil-producing region. A framework is produced that describes practices that characterize collaborative environmental management might be employed to satisfy the stakeholders’ interests. The framework recommends critical factors, based on the findings, which may guide a collaborative environmental management in the oil producing regions. The recommendations are designed to re-define the practices of stakeholders in managing environmental issues in the oil producing regions, not as something wholly new, but as an approach essential for implementing a sustainable environmental policy. This research outcome may clarify areas for future research as well as to contribute to industry guidance in the area of collaborative environmental management.

Keywords: collaborative environmental management framework, case studies, document analysis, multinational oil companies, Nigerian oil producing regions, Nigerian government agencies, stakeholders analysis

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7700 Automated Building Internal Layout Design Incorporating Post-Earthquake Evacuation Considerations

Authors: Sajjad Hassanpour, Vicente A. González, Yang Zou, Jiamou Liu

Abstract:

Earthquakes pose a significant threat to both structural and non-structural elements in buildings, putting human lives at risk. Effective post-earthquake evacuation is critical for ensuring the safety of building occupants. However, current design practices often neglect the integration of post-earthquake evacuation considerations into the early-stage architectural design process. To address this gap, this paper presents a novel automated internal architectural layout generation tool that optimizes post-earthquake evacuation performance. The tool takes an initial plain floor plan as input, along with specific requirements from the user/architect, such as minimum room dimensions, corridor width, and exit lengths. Based on these inputs, firstly, the tool randomly generates different architectural layouts. Secondly, the human post-earthquake evacuation behaviour will be thoroughly assessed for each generated layout using the advanced Agent-Based Building Earthquake Evacuation Simulation (AB2E2S) model. The AB2E2S prototype is a post-earthquake evacuation simulation tool that incorporates variables related to earthquake intensity, architectural layout, and human factors. It leverages a hierarchical agent-based simulation approach, incorporating reinforcement learning to mimic human behaviour during evacuation. The model evaluates different layout options and provides feedback on evacuation flow, time, and possible casualties due to earthquake non-structural damage. By integrating the AB2E2S model into the automated layout generation tool, architects and designers can obtain optimized architectural layouts that prioritize post-earthquake evacuation performance. Through the use of the tool, architects and designers can explore various design alternatives, considering different minimum room requirements, corridor widths, and exit lengths. This approach ensures that evacuation considerations are embedded in the early stages of the design process. In conclusion, this research presents an innovative automated internal architectural layout generation tool that integrates post-earthquake evacuation simulation. By incorporating evacuation considerations into the early-stage design process, architects and designers can optimize building layouts for improved post-earthquake evacuation performance. This tool empowers professionals to create resilient designs that prioritize the safety of building occupants in the face of seismic events.

Keywords: agent-based simulation, automation in design, architectural layout, post-earthquake evacuation behavior

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7699 Current Status and Prospects of Further Control of Brucellosis in Humans and Domestic Ruminants in Bangladesh

Authors: A. K. M. Anisur Rahman

Abstract:

Brucellosis is an ancient and one of the world's most widespread zoonotic diseases affecting both, public health and animal production. Its current status in humans and domestic ruminants along with probable means to control further in Bangladesh are described. The true exposure prevalence of brucellosis in cattle, goats, and sheep seems to be low: 0.3% in cattle, 1% in goats and 1.2% in sheep. The true prevalence of brucellosis in humans was also reported to be around 2%. In such a low prevalence scenario both in humans and animals, the positive predictive values of the diagnostic tests were very low. The role Brucella species in the abortion of domestic ruminants is less likely. Still now, no Brucella spp. was isolated from animal and human samples. However, Brucella abortus DNA was detected from seropositive humans, cattle, and buffalo; milk of cow, goats, and gayals and semen of an infected bull. Consuming raw milk and unpasteurized milk products by Bangladeshi people are not common. Close contact with animals, artificial insemination using semen from infected bulls, grazing mixed species of animals together in the field and transboundary animal movement are important factors, which should be considered for the further control of this zoonosis in Bangladesh.

Keywords: brucellosis, control, human, zoonosis

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7698 Techno Economic Analysis for Solar PV and Hydro Power for Kafue Gorge Power Station

Authors: Elvis Nyirenda

Abstract:

This research study work was done to evaluate and propose an optimum measure to enhance the uptake of clean energy technologies such as solar photovoltaics, the study also aims at enhancing the country’s energy mix from the overdependence on hydro power which is susceptible to droughts and climate change challenges The country in the years 2015 - 2016 and 2018 - 2019 had received rainfall below average due to climate change and a shift in the weather pattern; this resulted in prolonged power outages and load shedding for more than 10 hours per day. ZESCO Limited, the utility company that owns infrastructure in the generation, transmission, and distribution of electricity (state-owned), is seeking alternative sources of energy in order to reduce the over-dependence on hydropower stations. One of the alternative sources of energy is Solar Energy from the sun. However, solar power is intermittent in nature and to smoothen the load curve, investment in robust energy storage facilities is of great importance to enhance security and reliability of electricity supply in the country. The methodology of the study looked at the historical performance of the Kafue gorge upper power station and utilised the hourly generation figures as input data for generation modelling in Homer software. The average yearly demand was derived from the available data on the system SCADA. The two dams were modelled as natural battery with the absolute state of charging and discharging determined by the available water resource and the peak electricity demand. The software Homer Energy System is used to simulate the scheme incorporating a pumped storage facility and Solar photovoltaic systems. The pumped hydro scheme works like a natural battery for the conservation of water, with the only losses being evaporation and water leakages from the dams and the turbines. To address the problem of intermittency on the solar resource and the non-availability of water for hydropower generation, the study concluded that utilising the existing Hydro power stations, Kafue Gorge upper and Kafue Gorge Lower to work conjunctively with Solar energy will reduce power deficits and increase the security of supply for the country. An optimum capacity of 350MW of solar PV can be integrated while operating Kafue Gorge power station in both generating and pumping mode to enable efficient utilisation of water at Kafue Gorge upper Dam and Kafue Gorge Lower dam.

Keywords: hydropower, solar power systems, energy storage, photovoltaics, solar irradiation, pumped hydro storage system, supervisory control and data acquisition, Homer energy

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7697 Nutritional Composition of Selected Wild Fruits from Minna Area of Niger State, Nigeria

Authors: John O. Jacob, Abdullahi Mann, Olanrewaju I. Adeshina, Mohammed M. Ndamitso

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Strychnos spinosa, Detarium microcarpum, Diospyros mespiliformis, Dialium guineese and Gardenia ternifolia are some of the wild fruits consume in the villages around Minna, Niger State. This investigation was conducted to assess the nutritional potentials of these fruits both for human consumption and for possible application in animal feed formulations. Standard analytical methods were employed in the determination of the various nutritional parameters. The proximate analysis results showed that the moisture contents ranged between (6.17-10.70%); crude fat (2.04-8.85%); crude protein (5.16-6.80%); crude fibre (7.23-19.65%); Ash (3.46-5.56%); carbohydrate (57.77-69.79%); energy value (284.49-407 kcal/mg); Vitamin C (7.2-39.93 mg/100g). The mineral analysis shows that the selected wild fruits could contribute considerable amount of both micro and macro elements to human nutrition potassium, sodium and calcium range between; potassium (343.27-764.71%); sodium (155.04-348.44%); calcium (52.47-101%). The macro element for the fruits pulp were in the order K>Na>Mg>Ca, hence, they could be included in diet to supplement daily nutrient requirement and in animal feed formulations. The domestication of these fruits is also encouraged.

Keywords: mineral, micro-elements, macro-elements, feed suppleme

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7696 Fires in Historic Buildings: Assessment of Evacuation of People by Computational Simulation

Authors: Ivana R. Moser, Joao C. Souza

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Building fires are random phenomena that can be extremely violent, and safe evacuation of people is the most guaranteed tactic in saving lives. The correct evacuation of buildings, and other spaces occupied by people, means leaving the place in a short time and by the appropriate way. It depends on the perception of spaces by the individual, the architectural layout and the presence of appropriate routing systems. As historical buildings were constructed in other times, when, as in general, the current security requirements were not available yet, it is necessary to adapt these spaces to make them safe. Computer models of evacuation simulation are widely used tools for assessing the safety of people in a building or agglomeration sites and these are associated with the analysis of human behaviour, makes the results of emergency evacuation more correct and conclusive. The objective of this research is the performance evaluation of historical interest buildings, regarding the safe evacuation of people, through computer simulation, using PTV Viswalk software. The buildings objects of study are the Colégio Catarinense, centennial building, located in the city of Florianópolis, Santa Catarina / Brazil. The software used uses the variables of human behaviour, such as: avoid collision with other pedestrians and avoid obstacles. Scenarios were run on the three-dimensional models and the contribution to safety in risk situations was verified as an alternative measure, especially in the impossibility of applying those measures foreseen by the current fire safety codes in Brazil. The simulations verified the evacuation time in situations of normality and emergency situations, as well as indicate the bottlenecks and critical points of the studied buildings, to seek solutions to prevent and correct these undesirable events. It is understood that adopting an advanced computational performance-based approach promotes greater knowledge of the building and how people behave in these specific environments, in emergency situations.

Keywords: computer simulation, escape routes, fire safety, historic buildings, human behavior

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7695 Dwelling in the Built Environment: The Resilience by Design in Modular Thinking toward an Adaptive Alternatives

Authors: Tzen-Ying Ling

Abstract:

Recently, the resilience of dwellings in urban areas has been deliberated, as to accommodate the growing demand for changing the demography and rapid urbanization. The need to incorporate sustainability and cleaner production thinking have intensified to mitigate climate risks and satisfy the demand for housing. The modular thinking satisfies both the pressing call for fast-tracked housing stocks; while meeting the goal of more sustainable production. In the other side, the importance of the dwelling as a podium for well-being and social connectedness are sought to explore the key human/environment design thinking for the modular system in dwelling. We argue the best practice incorporates the concept of systemic components thinking. The fieldwork reported in this paper illustrates the process of the case study in a modular dwelling unit prototype development; focusing on the systemic frame system design process and adjustment recommendation hereafter. Using a case study method, the study identified that: (1) inclusive human dimensional factoring through systemic design thinking results in affordable implementations possibilities. (2) The environmental dimension encourages the place-based solution suited for the locality and the increasing demand for dwelling in the urban system. (3) Prototype design consideration avails module system component as dwelling construction alternative. (4) Building code often acts as an inhibitor for such dwelling units by the restriction in lot sizes and units placement. The demand for fast-track dwelling construction and cleaner production decisively outweighs the code inhibition; we further underscored the sustainability implication of the alternative prototype as the core of this study. The research suggests that modular thinking results in a resilient solution suited for the locality and the increasing demand for dwelling in the urban system.

Keywords: system prototype, urban resilience, human/environment dimension, modular thinking, dwelling alternative

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7694 The Use of Political Savviness in Dealing with Workplace Ostracism: A Social Information Processing Perspective

Authors: Amy Y. Wang, Eko L. Yi

Abstract:

Can vicarious experiences of workplace ostracism affect employees’ willingness to voice? Given the increasingly interdependent nature of the modern workplace in which employees rely on social interactions to fulfill organizational goals, workplace ostracism –the extent to which an individual perceives that he or she is ignored or excluded by others in the workplace– has garnered significant interest from scholars and practitioners alike. Extending beyond conventional studies that largely focus on the perspectives and outcomes of ostracized targets, we address the indirect effects of workplace ostracism on third-party employees embedded in the same social context. Using a social information processing approach, we propose that the ostracism of coworkers acts as political information that influences third-party employees in their decisions to engage in risky and discretionary behaviors such as employee voice. To make sense of and to navigate through experiences of workplace ostracism, we posit that both political understanding and political skill allow third party employees to minimize the risks and uncertainty of voicing. This conceptual model was tested by a study involving 154 supervisor-subordinate dyads of a publicly listed bio-technology firm located in Mainland China. Each supervisor and their direct subordinates composed of a work team; each team had a minimum of two subordinates and a maximum of four subordinates. Human resources used the master list to distribute the ID coded questionnaires to the matching names. All studied constructs were measured using existing scales proved effective in previous literature. Hypotheses were tested using Confirmatory Factor Analysis and Hierarchal Multiple Regression. All three hypotheses were supported which showed that employees were less likely to engage in voice behaviors when their coworkers reported having experienced ostracism in the workplace. Results also showed a significant three-way interaction between political understanding and political skill on the relationship between coworkers’ ostracism and employee voice, indicating that political savviness is a valuable resource in mitigating ostracism’s negative and indirect effects. Our results illustrated that an employee’s coworkers being ostracized indeed adversely impacted his or her own voice behavior. However, not all individuals reacted passively to the social context; rather, we found that politically savvy individuals – possessing both political understanding and political skill – and their voice behaviors were less impacted by ostracism in their work environment. At the same time, we found that having only political understanding or only political skill was significantly less effective in mitigating ostracism’s negative effects, suggesting a necessary duality of political knowledge and political skill in combatting ostracism. Organizational implications, recommendations, and future research ideas are also discussed.

Keywords: employee voice, organizational politics, social information processing, workplace ostracism

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7693 An Inquiry into the Usage of Complex Systems Models to Examine the Effects of the Agent Interaction in a Political Economic Environment

Authors: Ujjwall Sai Sunder Uppuluri

Abstract:

Group theory is a powerful tool that researchers can use to provide a structural foundation for their Agent Based Models. These Agent Based models are argued by this paper to be the future of the Social Science Disciplines. More specifically, researchers can use them to apply evolutionary theory to the study of complex social systems. This paper illustrates one such example of how theoretically an Agent Based Model can be formulated from the application of Group Theory, Systems Dynamics, and Evolutionary Biology to analyze the strategies pursued by states to mitigate risk and maximize usage of resources to achieve the objective of economic growth. This example can be applied to other social phenomena and this makes group theory so useful to the analysis of complex systems, because the theory provides the mathematical formulaic proof for validating the complex system models that researchers build and this will be discussed by the paper. The aim of this research, is to also provide researchers with a framework that can be used to model political entities such as states on a 3-dimensional plane. The x-axis representing resources (tangible and intangible) available to them, y the risks, and z the objective. There also exist other states with different constraints pursuing different strategies to climb the mountain. This mountain’s environment is made up of risks the state faces and resource endowments. This mountain is also layered in the sense that it has multiple peaks that must be overcome to reach the tallest peak. A state that sticks to a single strategy or pursues a strategy that is not conducive to the climbing of that specific peak it has reached is not able to continue advancement. To overcome the obstacle in the state’s path, it must innovate. Based on the definition of a group, we can categorize each state as being its own group. Each state is a closed system, one which is made up of micro level agents who have their own vectors and pursue strategies (actions) to achieve some sub objectives. The state also has an identity, the inverse being anarchy and/or inaction. Finally, the agents making up a state interact with each other through competition and collaboration to mitigate risks and achieve sub objectives that fall within the primary objective. Thus, researchers can categorize the state as an organism that reflects the sum of the output of the interactions pursued by agents at the micro level. When states compete, they employ a strategy and that state which has the better strategy (reflected by the strategies pursued by her parts) is able to out-compete her counterpart to acquire some resource, mitigate some risk or fulfil some objective. This paper will attempt to illustrate how group theory combined with evolutionary theory and systems dynamics can allow researchers to model the long run development, evolution, and growth of political entities through the use of a bottom up approach.

Keywords: complex systems, evolutionary theory, group theory, international political economy

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7692 Development of a Highly Flexible, Sensitive and Stretchable Polymer Nanocomposite for Strain Sensing

Authors: Shaghayegh Shajari, Mehdi Mahmoodi, Mahmood Rajabian, Uttandaraman Sundararaj, Les J. Sudak

Abstract:

Although several strain sensors based on carbon nanotubes (CNTs) have been reported, the stretchability and sensitivity of these sensors have remained as a challenge. Highly stretchable and sensitive strain sensors are in great demand for human motion monitoring and human-machine interface. This paper reports the fabrication and characterization of a new type of strain sensors based on a stretchable fluoropolymer / CNT nanocomposite system made via melt-mixing technique. Electrical and mechanical characterizations were obtained. The results showed that this nanocomposite sensor has high stretchability up to 280% of strain at an optimum level of filler concentration. The piezoresistive properties and the strain sensing mechanism of the strain sensor were investigated using Electrochemical Impedance Spectroscopy (EIS). High sensitivity was obtained (gauge factor as large as 12000 under 120% applied strain) in particular at the concentrations above the percolation threshold. Due to the tunneling effect, a non- linear piezoresistivity was observed at high concentrations of CNT loading. The nanocomposites with good conductivity and lightweight could be a promising candidate for strain sensing applications.

Keywords: carbon nanotubes, fluoropolymer, piezoresistive, strain sensor

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7691 The Impact of Corporate Social Responsibility Perception on Organizational Commitment: The Case of Cabin Crew in a Civil Aviation Company

Authors: Şeyda Kaya

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The aim of this study is to examine the relationship between corporate social responsibility perception and organizational commitment among Turkish cabin crew. At the same time, the social responsibility perception and organizational commitment scores of the participants were compared according to their gender, age, education level, title, and work experience. In the globalizing world, businesses have developed some innovative marketing methods in order to survive and strengthen their place in the market. Nowadays, consumers who are connected to the brand with an emotional bond rather than being just consumers. Corporate Social Responsibility Projects, on the one hand, provide social benefit, on the other hand, increase the brand awareness of businesses by providing credibility in the eyes of consumers. The rapid increase of competition, requires businesses to use their human resources, which is the most important resource to sustain their existence, in the most effective and efficient way. For this reason, the concept of ‘Organizational Commitment’ has become an important research topic for business and academics. Although there are studies in the literature to determine the effect of the perception of corporate social Responsibility on Organizational Commitment in Banking and Finance and Tourism sectors, there are no studies conducted specifically for the Turkish aviation sector to our best knowledge. Personal information form, CSR scale, Importance of CSR scale, Organizational commitment scale were used as data collection tools in the research. CSR Scale created by Türker (2006). was used to find out how employees felt about CSR. Importance of CSR Scale through a subscale of the Perceived Role of Ethics and Social Responsibility (PRESOR) that Etheredge (1999) converted into a two-factor framework, the significance of social responsibility for employees was assessed. Organizational Commitment Scale, Mowday, Steers, and Porter (1979) created the OCQ, which uses 15 measures to evaluate global commitment to the organization. As a result of the study, there is a significant positive relationship between the participants' CSR scale sub-dimensions, CSR to Employees, CSR to Customers, CSR to Society, CSR to Government, CSR to Natural Environment, CSR to Next Generation, CSR to Governmental Organizations, Importance of CSR, and Organizational Commitment scores. As a result; as the participants' Corporate Social Responsibility scores increase, their organizational commitment increases. To summarize the findings of our study, the scores obtained from the CSR scale and the scores obtained from the Organizational Commitment scale were found to have a positive and significant relationship. In other words, if the participants value the corporate social responsibility projects of the institution they work for and think that they spare time and effort, the importance they attach to the corporate social responsibility projects and their organizational commitment to the institution they work for, increase. Similarly, the scores obtained from the Importance of CSR and the scores obtained from the Organizational Commitment scale also have a positive and significant relationship. As the importance given to corporate social responsibility projects by the participants increases, their organizational commitment to the institution they work for also increases.

Keywords: corporate social responsibility, organizational commitment, Turkish cabin crew, aviation

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7690 Bilateral Telecontrol of AutoMerlin Mobile Robot Using Time Domain Passivity Control

Authors: Aamir Shahzad, Hubert Roth

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This paper is presenting the bilateral telecontrol of AutoMerlin Mobile Robot having communication delay. Passivity Observers has been designed to monitor the net energy at both ports of a two port network and if any or both ports become active making net energy negative, then the passivity controllers dissipate the proper energy to make the overall system passive in the presence of time delay. The environment force is modeled and sent back to human operator so that s/he can feel it and has additional information about the environment in the vicinity of mobile robot. The experimental results have been presented to show the performance and stability of bilateral controller. The results show the whenever the passivity observers observe active behavior then the passivity controller come into action to neutralize the active behavior to make overall system passive.

Keywords: bilateral control, human operator, haptic device, communication network, time domain passivity control, passivity observer, passivity controller, time delay, mobile robot, environment force

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7689 Automating 2D CAD to 3D Model Generation Process: Wall pop-ups

Authors: Mohit Gupta, Chialing Wei, Thomas Czerniawski

Abstract:

In this paper, we have built a neural network that can detect walls on 2D sheets and subsequently create a 3D model in Revit using Dynamo. The training set includes 3500 labeled images, and the detection algorithm used is YOLO. Typically, engineers/designers make concentrated efforts to convert 2D cad drawings to 3D models. This costs a considerable amount of time and human effort. This paper makes a contribution in automating the task of 3D walls modeling. 1. Detecting Walls in 2D cad and generating 3D pop-ups in Revit. 2. Saving designer his/her modeling time in drafting elements like walls from 2D cad to 3D representation. An object detection algorithm YOLO is used for wall detection and localization. The neural network is trained over 3500 labeled images of size 256x256x3. Then, Dynamo is interfaced with the output of the neural network to pop-up 3D walls in Revit. The research uses modern technological tools like deep learning and artificial intelligence to automate the process of generating 3D walls without needing humans to manually model them. Thus, contributes to saving time, human effort, and money.

Keywords: neural networks, Yolo, 2D to 3D transformation, CAD object detection

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7688 Effects of Cannabis and Cocaine on Driving Related Tasks of Perception, Cognition, and Action

Authors: Michelle V. Tomczak, Reyhaneh Bakhtiari, Aaron Granley, Anthony Singhal

Abstract:

Objective: Cannabis and cocaine are associated with a range of mental and physical effects that can impair aspects of human behavior. Driving is a complex cognitive behavior that is an essential part of everyday life and can be broken down into many subcomponents, each of which can uniquely impact road safety. With the growing movement of jurisdictions to legalize cannabis, there is an increased focus on impairment and driving. The purpose of this study was to identify driving-related cognitive-performance deficits that are impacted by recreational drug use. Design and Methods: With the assistance of law enforcement agencies, we recruited over 300 participants under the influence of various drugs including cannabis and cocaine. These individuals performed a battery of computer-based tasks scientifically proven to be re-lated to on-road driving performance and designed to test response-speed, memory processes, perceptual-motor skills, and decision making. Data from a control group with healthy non-drug using adults was collected as well. Results: Compared to controls, the drug group showed def-icits in all tasks. The data also showed clear differences between the cannabis and cocaine groups where cannabis users were faster, and performed better on some aspects of the decision-making and perceptual-motor tasks. Memory performance was better in the cocaine group for simple tasks but not more complex tasks. Finally, the participants who consumed both drugs performed most similarly to the cannabis group. Conclusions: Our results show distinct and combined effects of cannabis and cocaine on human performance relating to driving. These dif-ferential effects are likely related to the unique effects of each drug on the human brain and how they distinctly contribute to mental states. Our results have important implications for road safety associated with driver impairment.

Keywords: driving, cognitive impairment, recreational drug use, cannabis and cocaine

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7687 Disinformation’s Threats to Democracy in Central Africa: Case Studies from Cameroon and Central African Republic

Authors: Simont Toussi

Abstract:

Cameroon and the Central African Republic arebound by the provisions of many regional and international charters, which condemn the manipulation of information, obstacles to access reliable information, or the limitation of freedoms of expression and opinion. These two countries also have constitutional guarantees for free speech and access to true and liable information. However, they are yet to define specific policies and regulations for access to information, disinformation, or misinformation. Yet, certain countries’ laws and regulations related to information and communication technologies, to criminal procedures, to terrorism, or intelligence services contain provisions that rather hider human rights by condemning false information. Like many other African countries, Cameroon and the Central African Republic face a profound democratic regression, and governments use multiple methods to stifle online discourse and digital rights. Despite the increased uptake of digital tools for political participation, there is a lack of interactivity and adoption of these tools. This enables a scarcity of information and creates room for the spreading of disinformation in the public space, hamperingdemocracy and the respect for human rights. This research aims to analyse the adequacy of stakeholders’ responses to disinformation in Cameroon and the Central African Republic in periods of political contestation, such as elections and anti-government protests, to highlight the nature, perpetrators, strategies, and channels of disinformation, as well as its effects on democratic actors, including civil society, bloggers, government critics, activists, and other human rights defenders. The study follows a qualitative method with literature review, content analysis, andkey informant’sinterviews with stakeholders’ representatives, emphasized crowdsourcing as a data and information collecting method in the two countries.

Keywords: disinformation, democracy, political manipulation, social media, media, fake news, central Africa, cameroon, misinformation, free speech

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7686 Role of Human Epididymis Protein 4 as a Biomarker in the Diagnosis of Ovarian Cancer

Authors: Amar Ranjan, Julieana Durai, Pranay Tanwar

Abstract:

Background &Introduction: Ovarian cancer is one of the most common malignant tumor in the female. 70% of the cases of ovarian cancer are diagnosed at an advanced stage. The five-year survival rate associated with ovarian cancer is less than 30%. The early diagnosis of ovarian cancer becomes a key factor in improving the survival rate of patients. Presently, CAl25 (carbohydrate antigen125) is used for the diagnosis and therapeutic monitoring of ovarian cancer, but its sensitivity and specificity is not ideal. The introduction of HE4, human epididymis protein 4 has attracted much attention. HE4 has a sensitivity and specificity of 72.9% and 95% for differentiating between benign and malignant adnexal masses, which is better than CA125 detection.  Methods: Serum HE4 and CA -125 were estimated using the chemiluminescence method. Our cases were 40 epithelial ovarian cancer, 9 benign ovarian tumor, 29 benign gynaecological diseases and 13 healthy individuals. This group include healthy woman those who have undergoing family planning and menopause-related medical consultations and they are negative for ovarian mass. Optimal cut off values for HE4 and CA125 were 55.89pmol/L and 40.25U/L respectively (determined by statistical analysis). Results: The level of HE4 was raised in all ovarian cancer patients (n=40) whereas CA125 levels were normal in 6/40 ovarian cancer patients, which were the cases of OC confirmed by histopathology. There is a significant decrease in the level of HE4 with comparison to CA125 in benign ovarian tumor cases. Both the levels of HE4 and CA125 were raised in the nonovarian cancer group, which includes cancer of endometrium and cervix. In the healthy group, HE4 was normal in all patients except in one case of the rudimentary horn, and the reason for this raised HE4 level is due to the incomplete development of uterus whereas CA125 was raised in 3 cases. Conclusions: Findings showed that the serum level of HE4 is an important indicator in the diagnosis of ovarian cancer, and it also distinguishes between benign and malignant pelvic masses. However, a combination of HE4 and CA125 panel will be extremely valuable in improving the diagnostic efficiency of ovarian cancer. These findings of our study need to be validated in the larger cohort of patients.

Keywords: human epididymis protein 4, ovarian cancer, diagnosis, benign lesions

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7685 Determination of the Gain in Learning the Free-Fall Motion of Bodies by Applying the Resource of Previous Concepts

Authors: Ricardo Merlo

Abstract:

In this paper, we analyzed the different didactic proposals for teaching about the free fall motion of bodies available online. An important aspect was the interpretation of the direction and sense of the acceleration of gravity and of the falling velocity of a body, which is why we found different applications of the Cartesian reference system used and also different graphical presentations of the velocity as a function of time and of the distance traveled vertically by the body in the period of time that it was dropped from a height h0. In this framework, a survey of previous concepts was applied to a voluntary group of first-year university students of an Engineering degree before and after the development of the class of the subject in question. Then, Hake's index (0.52) was determined, which resulted in an average learning gain from the meaningful use of the reference system and the respective graphs of v=ƒ (t) and h=ƒ (t).

Keywords: didactic gain, free–fall, physics teaching, previous knowledge

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7684 Development of a Human Skin Explant Model for Drug Metabolism and Toxicity Studies

Authors: K. K. Balavenkatraman, B. Bertschi, K. Bigot, A. Grevot, A. Doelemeyer, S. D. Chibout, A. Wolf, F. Pognan, N. Manevski, O. Kretz, P. Swart, K. Litherland, J. Ashton-Chess, B. Ling, R. Wettstein, D. J. Schaefer

Abstract:

Skin toxicity is poorly detected during preclinical studies, and drug-induced side effects in humans such as rashes, hyperplasia or more serious events like bullous pemphigus or toxic epidermal necrolysis represent an important hurdle for clinical development. In vitro keratinocyte-based epidermal skin models are suitable for the detection of chemical-induced irritancy, but do not recapitulate the biological complexity of full skin and fail to detect potential serious side-effects. Normal healthy skin explants may represent a valuable complementary tool, having the advantage of retaining the full skin architecture and the resident immune cell diversity. This study investigated several conditions for the maintenance of good morphological structure after several days of culture and the retention of phase II metabolism for 24 hours in skin explants in vitro. Human skin samples were collected with informed consent from patients undergoing plastic surgery and immediately transferred and processed in our laboratory by removing the underlying dermal fat. Punch biopsies of 4 mm diameter were cultured in an air-liquid interface using transwell filters. Different cultural conditions such as the effect of calcium, temperature and cultivation media were tested for a period of 14 days and explants were histologically examined after Hematoxylin and Eosin staining. Our results demonstrated that the use of Williams E Medium at 32°C maintained the physiological integrity of the skin for approximately one week. Upon prolonged incubation, the upper layers of the epidermis become thickened and some dead cells are present. Interestingly, these effects were prevented by addition of EGFR inhibitors such as Afatinib or Erlotinib. Phase II metabolism of the skin such as glucuronidation (4-methyl umbeliferone), sulfation (minoxidil), N-acetyltransferase (p-toluidene), catechol methylation (2,3-dehydroxy naphthalene), and glutathione conjugation (chlorodinitro benzene) were analyzed by using LCMS. Our results demonstrated that the human skin explants possess metabolic activity for a period of at least 24 hours for all the substrates tested. A time course for glucuronidation with 4-methyl umbeliferone was performed and a linear correlation was obtained over a period of 24 hours. Longer-term culture studies will indicate the possible evolution of such metabolic activities. In summary, these results demonstrate that human skin explants maintain a normal structure for several days in vitro and are metabolically active for at least the first 24 hours. Hence, with further characterisation, this model may be suitable for the study of drug-induced toxicity.

Keywords: human skin explant, phase II metabolism, epidermal growth factor receptor, toxicity

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7683 Verification and Proposal of Information Processing Model Using EEG-Based Brain Activity Monitoring

Authors: Toshitaka Higashino, Naoki Wakamiya

Abstract:

Human beings perform a task by perceiving information from outside, recognizing them, and responding them. There have been various attempts to analyze and understand internal processes behind the reaction to a given stimulus by conducting psychological experiments and analysis from multiple perspectives. Among these, we focused on Model Human Processor (MHP). However, it was built based on psychological experiments and thus the relation with brain activity was unclear so far. To verify the validity of the MHP and propose our model from a viewpoint of neuroscience, EEG (Electroencephalography) measurements are performed during experiments in this study. More specifically, first, experiments were conducted where Latin alphabet characters were used as visual stimuli. In addition to response time, ERPs (event-related potentials) such as N100 and P300 were measured by using EEG. By comparing cycle time predicted by the MHP and latency of ERPs, it was found that N100, related to perception of stimuli, appeared at the end of the perceptual processor. Furthermore, by conducting an additional experiment, it was revealed that P300, related to decision making, appeared during the response decision process, not at the end. Second, by experiments using Japanese Hiragana characters, i.e. Japan's own phonetic symbols, those findings were confirmed. Finally, Japanese Kanji characters were used as more complicated visual stimuli. A Kanji character usually has several readings and several meanings. Despite the difference, a reading-related task and a meaning-related task exhibited similar results, meaning that they involved similar information processing processes of the brain. Based on those results, our model was proposed which reflects response time and ERP latency. It consists of three processors: the perception processor from an input of a stimulus to appearance of N100, the cognitive processor from N100 to P300, and the decision-action processor from P300 to response. Using our model, an application system which reflects brain activity can be established.

Keywords: brain activity, EEG, information processing model, model human processor

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7682 Design of an Acoustic System for Small-Scale Power Plants

Authors: Mohammadreza Judaki, Hosein Mohammadnezhad Shourkaei

Abstract:

Usually, noise generated by industrial units, is a pollution and disturbs people and causes problems for human health and sometimes these units will be closed because they cannot eliminate this pollution. Small-scale power plants usually are built close to residential areas, and noise generated by these power plants is an important factor in choosing their location and their design. Materials used to reduce noise are studied by measuring their absorption and reflection index numerically and experimentally. We can use MIKI model (Yasushi Miki, 1990) to simulate absorption index by using software like Ansys or Soundflow and compare calculation results with experimental simulation data. We consider high frequency sounds of power plant engines octave band diagram because dB value of high frequency noise is more noticeable for human ears. To prove this, in this study we first will study calculating octave band of engines exhausts and then we will study acoustic behavior of materials that we will use in high frequencies and this will give us our optimum noise reduction plan.

Keywords: acoustic materials, eliminating engine noise, octave level diagram, power plant noise

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7681 Spatial Distribution of Ambient BTEX Concentrations at an International Airport in South Africa

Authors: Raeesa Moolla, Ryan S. Johnson

Abstract:

Air travel, and the use of airports, has experienced proliferative growth in the past few decades, resulting in the concomitant release of air pollutants. Air pollution needs to be monitored because of the known relationship between exposure to air pollutants and increased adverse effects on human health. This study monitored a group of volatile organic compounds (VOCs); specifically BTEX (viz. benzene, toluene, ethyl-benzene and xylenes), as many are detrimental to human health. Through the use of passive sampling methods, the spatial variability of BTEX within an international airport was investigated, in order to determine ‘hotspots’ where occupational exposure to BTEX may be intensified. The passive sampling campaign revealed BTEXtotal concentrations ranged between 12.95–124.04 µg m-3. Furthermore, BTEX concentrations were dispersed heterogeneously within the airport. Due to the slow wind speeds recorded (1.13 m.s-1); the hotspots were located close to their main BTEX sources. The main hotspot was located over the main apron of the airport. Employees working in this area may be chronically exposed to these emissions, which could be potentially detrimental to their health.

Keywords: air pollution, air quality, hotspot monitoring, volatile organic compounds

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7680 A Qualitative Approach to Engineering Design Issues, Problems, and Solutions

Authors: M. U. Arshid, M. A. Kamal

Abstract:

The engineering design process is the activities formulation, to help an engineer raising a plan with a specified goal and performance. The engineering design process is a multi-stage course of action including the conceptualization, research, feasibility studies, establishment of design parameters, preliminary and finally the detailed design. It is a progression from the abstract to the concrete; starting with probably abstract ideas about need, and thereafter elaborating detailed specifications of the object that would satisfy the needs, identified. Engineering design issues, problems, and solutions are discussed in this paper using qualitative approach from an information structure perspective. The objective is to identify the problems, to analyze them and propose solutions by integrating; innovation, practical experience, time and resource management, communications skills, isolating the problem in coordination with all stakeholders. Consequently, this would be beneficial for the engineering community to improve the Engineering design practices.

Keywords: engineering design, engineering design issues, innovation, public sector projects

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7679 Stakeholder-Driven Development of a One Health Platform to Prevent Non-Alimentary Zoonoses

Authors: A. F. G. Van Woezik, L. M. A. Braakman-Jansen, O. A. Kulyk, J. E. W. C. Van Gemert-Pijnen

Abstract:

Background: Zoonoses pose a serious threat to public health and economies worldwide, especially as antimicrobial resistance grows and newly emerging zoonoses can cause unpredictable outbreaks. In order to prevent and control emerging and re-emerging zoonoses, collaboration between veterinary, human health and public health domains is essential. In reality however, there is a lack of cooperation between these three disciplines and uncertainties exist about their tasks and responsibilities. The objective of this ongoing research project (ZonMw funded, 2014-2018) is to develop an online education and communication One Health platform, “eZoon”, for the general public and professionals working in veterinary, human health and public health domains to support the risk communication of non-alimentary zoonoses in the Netherlands. The main focus is on education and communication in times of outbreak as well as in daily non-outbreak situations. Methods: A participatory development approach was used in which stakeholders from veterinary, human health and public health domains participated. Key stakeholders were identified using business modeling techniques previously used for the design and implementation of antibiotic stewardship interventions and consisted of a literature scan, expert recommendations, and snowball sampling. We used a stakeholder salience approach to rank stakeholders according to their power, legitimacy, and urgency. Semi-structured interviews were conducted with stakeholders (N=20) from all three disciplines to identify current problems in risk communication and stakeholder values for the One Health platform. Interviews were transcribed verbatim and coded inductively by two researchers. Results: The following key values were identified (but were not limited to): (a) need for improved awareness of veterinary and human health of each other’s fields, (b) information exchange between veterinary and human health, in particularly at a regional level; (c) legal regulations need to match with daily practice; (d) professionals and general public need to be addressed separately using tailored language and information; (e) information needs to be of value to professionals (relevant, important, accurate, and have financial or other important consequences if ignored) in order to be picked up; and (f) need for accurate information from trustworthy, centrally organised sources to inform the general public. Conclusion: By applying a participatory development approach, we gained insights from multiple perspectives into the main problems of current risk communication strategies in the Netherlands and stakeholder values. Next, we will continue the iterative development of the One Health platform by presenting key values to stakeholders for validation and ranking, which will guide further development. We will develop a communication platform with a serious game in which professionals at the regional level will be trained in shared decision making in time-critical outbreak situations, a smart Question & Answer (Q&A) system for the general public tailored towards different user profiles, and social media to inform the general public adequately during outbreaks.

Keywords: ehealth, one health, risk communication, stakeholder, zoonosis

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7678 Identification, Synthesis, and Biological Evaluation of the Major Human Metabolite of NLRP3 Inflammasome Inhibitor MCC950

Authors: Manohar Salla, Mark S. Butler, Ruby Pelingon, Geraldine Kaeslin, Daniel E. Croker, Janet C. Reid, Jong Min Baek, Paul V. Bernhardt, Elizabeth M. J. Gillam, Matthew A. Cooper, Avril A. B. Robertson

Abstract:

MCC950 is a potent and selective inhibitor of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome that shows early promise for treatment of inflammatory diseases. The identification of major metabolites of lead molecule is an important step during drug development process. It provides an information about the metabolically labile sites in the molecule and thereby helping medicinal chemists to design metabolically stable molecules. To identify major metabolites of MCC950, the compound was incubated with human liver microsomes and subsequent analysis by (+)- and (−)-QTOF-ESI-MS/MS revealed a major metabolite formed due to hydroxylation on 1,2,3,5,6,7-hexahydro-s-indacene moiety of MCC950. This major metabolite can lose two water molecules and three possible regioisomers were synthesized. Co-elution of major metabolite with each of the synthesized compounds using HPLC-ESI-SRM-MS/MS revealed the structure of the metabolite (±) N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. Subsequent synthesis of individual enantiomers and coelution in HPLC-ESI-SRM-MS/MS using a chiral column revealed the metabolite was R-(+)- N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. To study the possible cytochrome P450 enzyme(s) responsible for the formation of major metabolite, MCC950 was incubated with a panel of cytochrome P450 enzymes. The result indicated that CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C18, CYP2C19, CYP2J2 and CYP3A4 are most likely responsible for the formation of the major metabolite. The biological activity of the major metabolite and the other synthesized regioisomers was also investigated by screening for for NLRP3 inflammasome inhibitory activity and cytotoxicity. The major metabolite had 170-fold less inhibitory activity (IC50-1238 nM) than MCC950 (IC50-7.5 nM). Interestingly, one regioisomer had shown nanomolar inhibitory activity (IC50-232 nM). However, no evidence of cytotoxicity was observed with any of these synthesized compounds when tested in human embryonic kidney 293 cells (HEK293) and human liver hepatocellular carcinoma G2 cells (HepG2). These key findings give an insight into the SAR of the hexahydroindacene moiety of MCC950 and reveal a metabolic soft spot which could be blocked by chemical modification.

Keywords: Cytochrome P450, inflammasome, MCC950, metabolite, microsome, NLRP3

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