Search results for: plan making
Commenced in January 2007
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Edition: International
Paper Count: 6654

Search results for: plan making

444 Trophic Variations in Uptake and Assimilation of Cadmium, Manganese and Zinc: An Estuarine Food-Chain Radiotracer Experiment

Authors: K. O’Mara, T. Cresswell

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Nearly half of the world’s population live near the coast, and as a result, estuaries and coastal bays in populated or industrialized areas often receive metal pollution. Heavy metals have a chemical affinity for sediment particles and can be stored in estuarine sediments and become biologically available under changing conditions. Organisms inhabiting estuaries can be exposed to metals from a variety of sources including metals dissolved in water, bound to sediment or within contaminated prey. Metal uptake and assimilation responses can vary even between species that are biologically similar, making pollution effects difficult to predict. A multi-trophic level experiment representing a common Eastern Australian estuarine food chain was used to study the sources for Cd, Mn and Zn uptake and assimilation in organisms occupying several trophic levels. Sand cockles (Katelysia scalarina), school prawns (Metapenaeus macleayi) and sand whiting (Sillago ciliata) were exposed to radiolabelled seawater, suspended sediment and food. Three pulse-chase trials on filter-feeding sand cockles were performed using radiolabelled phytoplankton (Tetraselmis sp.), benthic microalgae (Entomoneis sp.) and suspended sediment. Benthic microalgae had lower metal uptake than phytoplankton during labelling but higher cockle assimilation efficiencies (Cd = 51%, Mn = 42%, Zn = 63 %) than both phytoplankton (Cd = 21%, Mn = 32%, Zn = 33%) and suspended sediment (except Mn; (Cd = 38%, Mn = 42%, Zn = 53%)). Sand cockles were also sensitive to uptake of Cd, Mn and Zn dissolved in seawater. Uptake of these metals from the dissolved phase was negligible in prawns and fish, with prawns only accumulating metals during moulting, which were then lost with subsequent moulting in the depuration phase. Diet appears to be the main source of metal assimilation in school prawns, with 65%, 54% and 58% assimilation efficiencies from Cd, Mn and Zn respectively. Whiting fed contaminated prawns were able to exclude the majority of the metal activity through egestion, with only 10%, 23% and 11% assimilation efficiencies from Cd, Mn and Zn respectively. The findings of this study support previous studies that find diet to be the dominant accumulation source for higher level trophic organisms. These results show that assimilation efficiencies can vary depending on the source of exposure; sand cockles assimilated more Cd, Mn, and Zn from the benthic diatom than phytoplankton and assimilation was higher in sand whiting fed prawns compared to artificial pellets. The sensitivity of sand cockles to metal uptake and assimilation from a variety of sources poses concerns for metal availability to predators ingesting the clam tissue, including humans. The high tolerance of sand whiting to these metals is reflected in their widespread presence in Eastern Australian estuaries, including contaminated estuaries such as Botany Bay and Port Jackson.

Keywords: cadmium, food chain, metal, manganese, trophic, zinc

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443 2,7-Diazaindole as a Photophysical Probe for Excited State Hydrogen/Proton Transfer

Authors: Simran Baweja, Bhavika Kalal, Surajit Maity

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Photoinduced tautomerization reactions have been the centre of attention among the scientific community over the past several decades because of their significance in various biological systems. 7-azaindole (7AI) is considered a model system for DNA base pairing and to understand the role of such tautomerization reactions in mutations. To the best of our knowledge, extensive studies have been carried out on 7-azaindole and its solvent clusters exhibiting proton/ hydrogen transfer in both solution as well as gas phases. Derivatives of the above molecule, like 2,7- and 2,6-diazaindoles are proposed to have even better photophysical properties due to the presence of -aza group on the 2nd position. However, there are studies in the solution phase that suggest the relevance of these molecules, but there are no experimental studies reported in the gas phase yet. In our current investigation, we present the first gas phase spectroscopic data of 2,7-diazaindole (2,7-DAI) and its solvent cluster (2,7-DAI-H2O). In this, we have employed state-of-the-art laser spectroscopic methods such as fluorescence excitation (LIF), dispersed fluorescence (DF), resonant two-photon ionization-time of flight mass spectrometry (2C-R2PI), photoionization efficiency spectroscopy (PIE), IR-UV double resonance spectroscopy, i.e., fluorescence-dip infrared spectroscopy (FDIR) and resonant ion-dip infrared spectroscopy (IDIR) to understand the electronic structure of the molecule. The origin band corresponding to the S1 ← S0 transition of the bare 2,7-DAI is found to be positioned at 33910 cm-1, whereas the origin band corresponding to S1 ← S0 transition of the 2,7-DAI-H2O is positioned at 33074 cm-1. The red-shifted transition in the case of solvent cluster suggests the enhanced feasibility of excited state hydrogen/ proton transfer. The ionization potential for the 2,7-DAI molecule is found to be 8.92 eV which is significantly higher than the previously reported 7AI (8.11 eV) molecule, making it a comparatively complex molecule to study. The ionization potential is reduced by 0.14 eV in the case of 2,7-DAI-H2O (8.78 eV) cluster compared to that of 2,7-DAI. Moreover, on comparison with the available literature values of 7AI, we found the origin band of 2,7-DAI and 2,7-DAI-H2O to be red-shifted by -729 and -280 cm-1 respectively. The ground and excited state N-H stretching frequencies of the 27DAI molecule were determined using fluorescence-dip infrared spectra (FDIR) and resonant ion dip infrared spectroscopy (IDIR), obtained at 3523 and 3467 cm-1, respectively. The lower value of vNH in the electronically excited state of 27DAI implies the higher acidity of the group compared to the ground state. Moreover, we have done extensive computational analysis, which suggests that the energy barrier in the excited state reduces significantly as we increase the number of catalytic solvent molecules (S= H2O, NH3) as well as the polarity of solvent molecules. We found that the ammonia molecule is a better candidate for hydrogen transfer compared to water because of its higher gas-phase basicity. Further studies are underway to understand the excited state dynamics and photochemistry of such N-rich chromophores.

Keywords: excited state hydrogen transfer, supersonic expansion, gas phase spectroscopy, IR-UV double resonance spectroscopy, laser induced fluorescence, photoionization efficiency spectroscopy

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442 Hydrographic Mapping Based on the Concept of Fluvial-Geomorphological Auto-Classification

Authors: Jesús Horacio, Alfredo Ollero, Víctor Bouzas-Blanco, Augusto Pérez-Alberti

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Rivers have traditionally been classified, assessed and managed in terms of hydrological, chemical and / or biological criteria. Geomorphological classifications had in the past a secondary role, although proposals like River Styles Framework, Catchment Baseline Survey or Stroud Rural Sustainable Drainage Project did incorporate geomorphology for management decision-making. In recent years many studies have been attracted to the geomorphological component. The geomorphological processes and their associated forms determine the structure of a river system. Understanding these processes and forms is a critical component of the sustainable rehabilitation of aquatic ecosystems. The fluvial auto-classification approach suggests that a river is a self-built natural system, with processes and forms designed to effectively preserve their ecological function (hydrologic, sedimentological and biological regime). Fluvial systems are formed by a wide range of elements with multiple non-linear interactions on different spatial and temporal scales. Besides, the fluvial auto-classification concept is built using data from the river itself, so that each classification developed is peculiar to the river studied. The variables used in the classification are specific stream power and mean grain size. A discriminant analysis showed that these variables are the best characterized processes and forms. The statistical technique applied allows to get an individual discriminant equation for each geomorphological type. The geomorphological classification was developed using sites with high naturalness. Each site is a control point of high ecological and geomorphological quality. The changes in the conditions of the control points will be quickly recognizable, and easy to apply a right management measures to recover the geomorphological type. The study focused on Galicia (NW Spain) and the mapping was made analyzing 122 control points (sites) distributed over eight river basins. In sum, this study provides a method for fluvial geomorphological classification that works as an open and flexible tool underlying the fluvial auto-classification concept. The hydrographic mapping is the visual expression of the results, such that each river has a particular map according to its geomorphological characteristics. Each geomorphological type is represented by a particular type of hydraulic geometry (channel width, width-depth ratio, hydraulic radius, etc.). An alteration of this geometry is indicative of a geomorphological disturbance (whether natural or anthropogenic). Hydrographic mapping is also dynamic because its meaning changes if there is a modification in the specific stream power and/or the mean grain size, that is, in the value of their equations. The researcher has to check annually some of the control points. This procedure allows to monitor the geomorphology quality of the rivers and to see if there are any alterations. The maps are useful to researchers and managers, especially for conservation work and river restoration.

Keywords: fluvial auto-classification concept, mapping, geomorphology, river

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441 Applications of Digital Tools, Satellite Images and Geographic Information Systems in Data Collection of Greenhouses in Guatemala

Authors: Maria A. Castillo H., Andres R. Leandro, Jose F. Bienvenido B.

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During the last 20 years, the globalization of economies, population growth, and the increase in the consumption of fresh agricultural products have generated greater demand for ornamentals, flowers, fresh fruits, and vegetables, mainly from tropical areas. This market situation has demanded greater competitiveness and control over production, with more efficient protected agriculture technologies, which provide greater productivity and allow us to guarantee the quality and quantity that is required in a constant and sustainable way. Guatemala, located in the north of Central America, is one of the largest exporters of agricultural products in the region and exports fresh vegetables, flowers, fruits, ornamental plants, and foliage, most of which were grown in greenhouses. Although there are no official agricultural statistics on greenhouse production, several thesis works, and congress reports have presented consistent estimates. A wide range of protection structures and roofing materials are used, from the most basic and simple ones for rain control to highly technical and automated structures connected with remote sensors for monitoring and control of crops. With this breadth of technological models, it is necessary to analyze georeferenced data related to the cultivated area, to the different existing models, and to the covering materials, integrated with altitude, climate, and soil data. The georeferenced registration of the production units, the data collection with digital tools, the use of satellite images, and geographic information systems (GIS) provide reliable tools to elaborate more complete, agile, and dynamic information maps. This study details a methodology proposed for gathering georeferenced data of high protection structures (greenhouses) in Guatemala, structured in four phases: diagnosis of available information, the definition of the geographic frame, selection of satellite images, and integration with an information system geographic (GIS). It especially takes account of the actual lack of complete data in order to obtain a reliable decision-making system; this gap is solved through the proposed methodology. A summary of the results is presented in each phase, and finally, an evaluation with some improvements and tentative recommendations for further research is added. The main contribution of this study is to propose a methodology that allows to reduce the gap of georeferenced data in protected agriculture in this specific area where data is not generally available and to provide data of better quality, traceability, accuracy, and certainty for the strategic agricultural decision öaking, applicable to other crops, production models and similar/neighboring geographic areas.

Keywords: greenhouses, protected agriculture, GIS, Guatemala, satellite image, digital tools, precision agriculture

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440 Pro-Environmental Behavioral Intention of Mountain Hikers to the Theory of Planned Behavior

Authors: Mohammad Ehsani, Iman Zarei, Soudabeh Moazemigoudarzi

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The aim of this study is to determine Pro-Environmental Behavioral Intention of Mountain Hikers to the Theory of Planned Behavior. According to many researchers nature-based recreation activities play a significant role in the tourism industry and have provided myriad opportunities for the protection of natural areas. It is essential to investigate individuals' behavior during such activities to avoid further damage to precious and dwindling natural resources. This study develops a robust model that provides a comprehensive understanding of the formation of pro-environmental behavioral intentions among climbers of Mount Damavand National Park in Iran. To this end, we combined the theory of planned behavior (TPB), value-belief-norm theory (VBN), and a hierarchical model of leisure constraints to predict individuals’ pro-environmental hiking behavior during outdoor recreation. It was used structural equation modeling to test the theoretical framework. A sample of 787 climbers was analyzed. Among the theory of planned behavior variables, perceived behavioral control showed the strongest association with behavioral intention (β = .57). This relationship indicates that if people feel they can have fewer negative impacts on national resources while hiking, it will result in more environmentally acceptable behavior. Subjective norms had a moderate positive impact on behavioral intention, indicating the importance of other people on the individual's behavior. Attitude had a small positive effect on intention. Ecological worldview positively influenced attitude and personal belief. Personal belief (awareness of consequences and ascribed responsibility) showed a positive association with TPB variables. Although the data showed a high average score in awareness of consequences (mean = 4.219 out of 5), evidence from Damavand Mount shows that there are many environmental issues that need addressing (e.g., vast amounts of garbage). National park managers need to make sure that their solutions result in awareness about proenvironmental behavior (PEB). Findings showed that negative relationship between constraints and all TPB predictors. Providing proper restrooms and parking spaces in campgrounds, strategies controlling limiting capacity and solutions for removing waste from high altitudes are helpful to decrease the negative impact of structural constraints. In order to address intrapersonal constraints, managers should provide opportunities to interest individuals in environmental activities, such as environmental celebrations or making documentaries about environmental issues. Moreover, promoting a culture of environmental protection in the Damavand Mount area would reduce interpersonal constraints. Overall, the proposed model improved the explanatory power of the TPB by predicting 64.7% of intention compared to the original TPB that accounted for 63.8% of the variance in intention.

Keywords: theory of planned behavior, pro-environmental behavior, national park, constraints

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439 Existential Affordances and Psychopathology: A Gibsonian Analysis of Dissociative Identity Disorder

Authors: S. Alina Wang

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A Gibsonian approach is used to understand the existential dimensions of the human ecological niche. Then, this existential-Gibsonian framework is applied to rethinking Hacking’s historical analysis of multiple personality disorder. This research culminates in a generalized account of psychiatric illness from an enactivist lens. In conclusion, reflections on the implications of this account on approaches to psychiatric treatment are mentioned. J.J. Gibson’s theory of affordances centered on affordances of sensorimotor varieties, which guide basic behaviors relative to organisms’ vital needs and physiological capacities (1979). Later theorists, notably Neisser (1988) and Rietveld (2014), expanded on the theory of affordances to account for uniquely human activities relative to the emotional, intersubjective, cultural, and narrative aspects of the human ecological niche. This research shows that these affordances are structured by what Haugeland (1998) calls existential commitments, which draws on Heidegger’s notion of dasein (1927) and Merleau-Ponty’s account of existential freedom (1945). These commitments organize the existential affordances that fill an individual’s environment and guide their thoughts, emotions, and behaviors. This system of a priori existential commitments and a posteriori affordances is called existential enactivism. For humans, affordances do not only elicit motor responses and appear as objects with instrumental significance. Affordances also, and possibly primarily, determine so-called affective and cognitive activities and structure the wide range of kinds (e.g., instrumental, aesthetic, ethical) of significances of objects found in the world. Then existential enactivism is applied to understanding the psychiatric phenomenon of multiple personality disorder (precursor of the current diagnosis of dissociative identity disorder). A reinterpretation of Hacking’s (1998) insights into the history of this particular disorder and his generalizations on the constructed nature of most psychiatric illness is taken on. Enactivist approaches sensitive to existential phenomenology can provide a deeper understanding of these matters. Conceptualizing psychiatric illness as strictly a disorder in the head (whether parsed as a disorder of brain chemicals or meaning-making capacities encoded in psychological modules) is incomplete. Rather, psychiatric illness must also be understood as a disorder in the world, or in the interconnected networks of existential affordances that regulate one’s emotional, intersubjective, and narrative capacities. All of this suggests that an adequate account of psychiatric illness must involve (1) the affordances that are the sources of existential hindrance, (2) the existential commitments structuring these affordances, and (3) the conditions of these existential commitments. Approaches to treatment of psychiatric illness would be more effective by centering on the interruption of normalized behaviors corresponding to affordances targeted as sources of hindrance, the development of new existential commitments, and the practice of new behaviors that erect affordances relative to these reformed commitments.

Keywords: affordance, enaction, phenomenology, psychiatry, psychopathology

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438 Testing Depression in Awareness Space: A Proposal to Evaluate Whether a Psychotherapeutic Method Based on Spatial Cognition and Imagination Therapy Cures Moderate Depression

Authors: Lucas Derks, Christine Beenhakker, Michiel Brandt, Gert Arts, Ruud van Langeveld

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Background: The method Depression in Awareness Space (DAS) is a psychotherapeutic intervention technique based on the principles of spatial cognition and imagination therapy with spatial components. The basic assumptions are: mental space is the primary organizing principle in the mind, and all psychological issues can be treated by first locating and by next relocating the conceptualizations involved. The most clinical experience was gathered over the last 20 years in the area of social issues (with the social panorama model). The latter work led to the conclusion that a mental object (image) gains emotional impact when it is placed more central, closer and higher in the visual field – and vice versa. Changing the locations of mental objects in space thus alters the (socio-) emotional meaning of the relationships. The experience of depression seems always associated with darkness. Psychologists tend to see the link between depression and darkness as a metaphor. However, clinical practice hints to the existence of more literal forms of darkness. Aims: The aim of the method Depression in Awareness Space is to reduce the distress of clients with depression in the clinical counseling practice, as a reliable alternative method of psychological therapy for the treatment of depression. The method Depression in Awareness Space aims at making dark areas smaller, lighter and more transparent in order to identify the problem or the cause of the depression which lies behind the darkness. It was hypothesized that the darkness is a subjective side-effect of the neurological process of repression. After reducing the dark clouds the real problem behind the depression becomes more visible, allowing the client to work on it and in that way reduce their feelings of depression. This makes repression of the issue obsolete. Results: Clients could easily get into their 'sadness' when asked to do so and finding the location of the dark zones proved pretty easy as well. In a recent pilot study with five participants with mild depressive symptoms (measured on two different scales and tested against an untreated control group with similar symptoms), the first results were also very promising. If the mental spatial approach to depression can be proven to be really effective, this would be very good news. The Society of Mental Space Psychology is now looking for sponsoring of an up scaled experiment. Conclusions: For spatial cognition and the research into spatial psychological phenomena, the discovery of dark areas can be a step forward. Beside out of pure scientific interest, it is great to know that this discovery has a clinical implication: when darkness can be connected to depression. Also, darkness seems to be more than metaphorical expression. Progress can be monitored over measurement tools that quantify the level of depressive symptoms and by reviewing the areas of darkness.

Keywords: depression, spatial cognition, spatial imagery, social panorama

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437 A Crowdsourced Homeless Data Collection System and Its Econometric Analysis

Authors: Praniil Nagaraj

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This paper proposes a method to collect homeless data using crowdsourcing and presents an approach to analyze the data, demonstrating its potential to strengthen existing and future policies aimed at promoting socio-economic equilibrium. The 2022 Annual Homeless Assessment Report (AHAR) to Congress highlighted alarming statistics, emphasizing the need for effective decision-making and budget allocation within local planning bodies known as Continuums of Care (CoC). This paper's contributions can be categorized into three main areas. Firstly, a unique method for collecting homeless data is introduced, utilizing a user-friendly smartphone app (currently available for Android). The app enables the general public to quickly record information about homeless individuals, including the number of people and details about their living conditions. The collected data, including date, time, and location, is anonymized and securely transmitted to the cloud. It is anticipated that an increasing number of users motivated to contribute to society will adopt the app, thus expanding the data collection efforts. Duplicate data is addressed through simple classification methods, and historical data is utilized to fill in missing information. The second contribution of this paper is the description of data analysis techniques applied to the collected data. By combining this new data with existing information, statistical regression analysis is employed to gain insights into various aspects, such as distinguishing between unsheltered and sheltered homeless populations, as well as examining their correlation with factors like unemployment rates, housing affordability, and labor demand. Initial data is collected in San Francisco, while pre-existing information is drawn from three cities: San Francisco, New York City, and Washington D.C., facilitating the conduction of simulations. The third contribution focuses on demonstrating the practical implications of the data processing results. The challenges faced by key stakeholders, including charitable organizations and local city governments, are taken into consideration. Two case studies are presented as examples. The first case study explores improving the efficiency of food and necessities distribution, as well as medical assistance, driven by charitable organizations. The second case study examines the correlation between micro-geographic budget expenditure by local city governments and homeless information to justify budget allocation and expenditures. The ultimate objective of this endeavor is to enable the continuous enhancement of the quality of life for the underprivileged. It is hoped that through increased crowdsourcing of data from the public, the Generosity Curve and the Need Curve will intersect, leading to a better world for all.

Keywords: crowdsourcing, homelessness, socio-economic policies, statistical analysis

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436 Maternity Care Model during Natural Disaster or Humanitarian Emegerncy Setting in Rural Pakistan

Authors: Humaira Maheen, Elizabeth Hoban, Catherine Bennette

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Background: Globally, role of Community Health Workers (CHW) as front line disaster health work force is underutilized. Developing countries which are at risk of natural disasters or humanitarian emergencies should lay down effective strategies especially to ensure adequate access to maternity care during crisis situation by using CHW as they are local, trained, and most of them possess a good relationship with the community. The Minimum Initial Service Package (MISP) is a set of universal guidelines that addresses women’s reproductive health needs during the first phase of an emergency. According to the MISP, pregnant women should have access to a skilled birth attendant and adequate transportation arrangements so they can access a maternity care facility. Pakistan is one of the few countries which has been severely affected by a number of natural disaster as well as humanitarian emergencies in last decade. Pakistan has a young and structured National Disaster Management System in place, where District Authorities play a vital role in disaster management. The District Health Department develops the contingency health plan for an emergency situation and implements it under the existing district health human resources (health workers and medical staff at the health facility) and infrastructure (health care facilities). Methods: A mixed methods study was conducted in rural villages of Sindh adjacent to the river Indus, and included in-depth interviews with 15 women who gave birth during the floods, structured interviews with 668 women who were pregnant during 2010-2014, and in-depth interviews with 25 community health workers (CHW) and 30 key informants. Results: Women said that giving birth in the relief camps during the floods was one of the most challenging times of their life. The district health department didn’t make transportation arrangement for labouring women from relief camp to the nearest health care facility. As a result 91.2% women gave birth in temporary shelters with the help of a traditional birth attendant (Dai) with no clean physical space available to birth. Of the 332 women who were pregnant at the time of the floods, 26 had adverse birth outcomes; 10 had miscarriages, 14 had stillbirths and there were four neonatal deaths. Conclusion: The district health department was not able to provide access to adequate maternity care during according to the international standard during the floods in 2011. We propose a model where CHWs will be used as frontline maternity care providers during any emergency or disaster situations in Pakistan. A separate "birthing station" should be mandatory in all district relief camps, managed by CHWs. Community midwives (CMW) would and the Lady Health Workers (LHW) would provide antenatal and postnatal care alongside, vaccination for pregnant women, neonates and children under five. There must be an ambulance facility for emergency obstetric cases and all district health facilities should have at least two medical staff identified and trained for emergency obstetric management. The District Health Department must provide clean birthing kits and regular and emergency contraceptives in the relief camps. Methods: A mixed methods study was conducted in rural villages of Sindh adjacent to the river Indus, and included in-depth interviews with 15 women who gave birth during the floods, structured interviews with 668 women who were pregnant during 2010-2014, and in-depth interviews with 25 community health workers (CHW) and 30 key informants. Results: Women said that giving birth in the relief camps during the floods was one of the most challenging times of their life. Nearly 91.2% women gave birth in temporary shelters with the help of a traditional birth attendant (Dai) with no clean physical space available to birth, and the health camp was mostly accessed by men and always overcrowded. There was no obstetric trained medical staff in the health camps or transportation provided to take women with complications to the nearest health facility. The rate of adverse outcome following disaster was 22.2% (95% CI: 8.62% – 42.2%) amongst 27 women who did not evacuate as compare to 7.91% (95% CI: 5.03% – 11.8%) among 278 women who lived in relief camp study participants. There were 27 women who evacuated on pre-flood warning and had 0% rate of adverse outcome. Conclusion: We propose a model where CHWs will be used as frontline maternity care providers during any emergency or disaster situations in Pakistan. A separate "birthing station" should be mandatory in all district relief camps, managed by CHWs. Community midwives (CMW) would and the Lady Health Workers (LHW) would provide antenatal and postnatal care alongside, vaccination for pregnant women, neonates and children under five. There must be an ambulance facility for emergency obstetric cases and all district health facilities should have at least two medical staff identified and trained for emergency obstetric management. The District Health Department must provide clean birthing kits and regular and emergency contraceptives in the relief camps.

Keywords: natural disaster, maternity care model, rural, Pakistan, community health workers

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435 Partisan Agenda Setting in Digital Media World

Authors: Hai L. Tran

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Previous research on agenda setting effects has often focused on the top-down influence of the media at the aggregate level, while overlooking the capacity of audience members to select media and content to fit their individual dispositions. The decentralized characteristics of online communication and digital news create more choices and greater user control, thereby enabling each audience member to seek out a unique blend of media sources, issues, and elements of messages and to mix them into a coherent individual picture of the world. This study examines how audiences use media differently depending on their prior dispositions, thereby making sense of the world in ways that are congruent with their preferences and cognitions. The current undertaking is informed by theoretical frameworks from two distinct lines of scholarship. According to the ideological migration hypothesis, individuals choose to live in communities with ideologies like their own to satisfy their need to belong. One tends to move away from Zip codes that are incongruent and toward those that are more aligned with one’s ideological orientation. This geographical division along ideological lines has been documented in social psychology research. As an extension of agenda setting, the agendamelding hypothesis argues that audiences seek out information in attractive media and blend them into a coherent narrative that fits with a common agenda shared by others, who think as they do and communicate with them about issues of public. In other words, individuals, through their media use, identify themselves with a group/community that they want to join. Accordingly, the present study hypothesizes that because ideology plays a role in pushing people toward a physical community that fits their need to belong, it also leads individuals to receive an idiosyncratic blend of media and be influenced by such selective exposure in deciding what issues are more relevant. Consequently, the individualized focus of media choices impacts how audiences perceive political news coverage and what they know about political issues. The research project utilizes recent data from The American Trends Panel survey conducted by Pew Research Center to explore the nuanced nature of agenda setting at the individual level and amid heightened polarization. Hypothesis testing is performed with both nonparametric and parametric procedures, including regression and path analysis. This research attempts to explore the media-public relationship from a bottom-up approach, considering the ability of active audience members to select among media in a larger process that entails agenda setting. It helps encourage agenda-setting scholars to further examine effects at the individual, rather than aggregate, level. In addition to theoretical contributions, the study’s findings are useful for media professionals in building and maintaining relationships with the audience considering changes in market share due to the spread of digital and social media.

Keywords: agenda setting, agendamelding, audience fragmentation, ideological migration, partisanship, polarization

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434 The Effect of the Performance Evolution System on the Productivity of Administrating and a Case Study

Authors: Ertuğrul Ferhat Yilmaz, Ali Riza Perçin

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In the business enterprises implemented modern business enterprise principles, the most important issues are increasing the performance of workers and getting maximum income. Through the twentieth century, rapid development of the sectors of data processing and communication and because of the free trade politics arising of multilateral business enterprises have canceled the economical borders and changed the local rivalry into the spherical rivalry. In this rivalry conditions, the business enterprises have to work active and productive in order to continue their existences. The employees worked at business enterprises have formed the most important factor of product. Therefore, the business enterprises inferring the importance of the human factors in order to increase the profit have used “the performance evolution system” to increase the success and development of the employees. The evolution of the performance is aimed to increase the manpower productive by using the employees in an active way. Furthermore, this system assists the wage politics implemented in business enterprise, determining the strategically plans in business enterprises through the short and long terms, being promoted and determining the educational needs of employees, making decisions as dismissing and work rotation. It requires a great deal of effort to catch the pace of change in the working realm and to keep up ourselves up-to-date. To get the quality in people,to have an effect in workplace depends largely on the knowledge and competence of managers and prospective managers. Therefore,managers need to use the performance evaluation systems in order to base their managerial decisions on sound data. This study aims at finding whether the organizations effectively use performance evaluation systms,how much importance is put on this issue and how much the results of the evaulations have an effect on employees. Whether the organizations have the advantage of competition and can keep on their activities depend to a large extent on how they effectively and efficiently use their employees.Therefore,it is of vital importance to evaluate employees' performance and to make them better according to the results of that evaluation. The performance evaluation system which evaluates the employees according to the criteria related to that organization has become one of the most important topics for management. By means of those important ends mentioned above,performance evaluation system seems to be a tool that can be used to improve the efficiency and effectiveness of organization. Because of its contribution to organizational success, thinking performance evaluation on the axis of efficiency shows the importance of this study on a different angle. In this study, we have explained performance evaluation system ,efficiency and the relation between those two concepts. We have also analyzed the results of questionnaires conducted on the textile workers in Edirne city.We have got positive answers from the questions about the effects of performance evaluation on efficiency.After factor analysis ,the efficiency and motivation which are determined as factors of performance evaluation system have the biggest variance (%19.703) in our sample. Thus, this study shows that objective performance evaluation increases the efficiency and motivation of employees.

Keywords: performance, performance evolution system, productivity, Edirne region

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433 The Sustained Utility of Japan's Human Security Policy

Authors: Maria Thaemar Tana

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The paper examines the policy and practice of Japan’s human security. Specifically, it asks the question: How does Japan’s shift towards a more proactive defence posture affect the place of human security in its foreign policy agenda? Corollary to this, how is Japan sustaining its human security policy? The objective of this research is to understand how Japan, chiefly through the Ministry of Foreign Affairs (MOFA) and JICA (Japan International Cooperation Agency), sustains the concept of human security as a policy framework. In addition, the paper also aims to show how and why Japan continues to include the concept in its overall foreign policy agenda. In light of the recent developments in Japan’s security policy, which essentially result from the changing security environment, human security appears to be gradually losing relevance. The paper, however, argues that despite the strategic challenges Japan faced and is facing, as well as the apparent decline of its economic diplomacy, human security remains to be an area of critical importance for Japanese foreign policy. In fact, as Japan becomes more proactive in its international affairs, the strategic value of human security also increases. Human security was initially envisioned to help Japan compensate for its weaknesses in the areas of traditional security, but as Japan moves closer to a more activist foreign policy, the soft policy of human security complements its hard security policies. Using the framework of neoclassical realism (NCR), the paper recognizes that policy-making is essentially a convergence of incentives and constraints at the international and domestic levels. The theory posits that there is no perfect 'transmission belt' linking material power on the one hand, and actual foreign policy on the other. State behavior is influenced by both international- and domestic-level variables, but while systemic pressures and incentives determine the general direction of foreign policy, they are not strong enough to affect the exact details of state conduct. Internal factors such as leaders’ perceptions, domestic institutions, and domestic norms, serve as intervening variables between the international system and foreign policy. Thus, applied to this study, Japan’s sustained utilization of human security as a foreign policy instrument (dependent variable) is essentially a result of systemic pressures (indirectly) (independent variables) and domestic processes (directly) (intervening variables). Two cases of Japan’s human security practice in two regions are examined in two time periods: Iraq in the Middle East (2001-2010) and South Sudan in Africa (2011-2017). The cases show that despite the different motives behind Japan’s decision to participate in these international peacekeepings ad peace-building operations, human security continues to be incorporated in both rhetoric and practice, thus demonstrating that it was and remains to be an important diplomatic tool. Different variables at the international and domestic levels will be examined to understand how the interaction among them results in changes and continuities in Japan’s human security policy.

Keywords: human security, foreign policy, neoclassical realism, peace-building

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432 Gender Construction in Contemporary Dystopian Fiction in Young Adult Literature: A South African Example

Authors: Johan Anker

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The purpose of this paper is to discuss the nature of gender construction in modern dystopian fiction, the development of this genre in Young Adult Literature and reasons for the enormous appeal on the adolescent readers. A recent award winning South African text in this genre, The Mark by Edith Bullring (2014), will be used as example while also comparing this text to international bestsellers like Divergent (Roth:2011), The Hunger Games (Collins:2008) and others. Theoretical insights from critics and academics in the field of children’s literature, like Ames, Coats, Bradford, Booker, Basu, Green-Barteet, Hintz, McAlear, McCallum, Moylan, Ostry, Ryan, Stephens and Westerfield will be referred to and their insights used as part of the analysis of The Mark. The role of relevant and recurring themes in this genre, like global concerns, environmental destruction, liberty, self-determination, social and political critique, surveillance and repression by the state or other institutions will also be referred to. The paper will shortly refer to the history and emergence of dystopian literature as genre in adult and young adult literature as part of the long tradition since the publishing of Orwell’s 1984 and Huxley’s Brave New World. Different factors appeal to adolescent readers in the modern versions of this hybrid genre for young adults: teenage protagonists who are questioning the underlying values of a flawed society like an inhuman or tyrannical government, a growing understanding of the society around them, feelings of isolation and the dynamic of relationships. This unease leads to a growing sense of the potential to act against society (rebellion), and of their role as agents in a larger community and independent decision-making abilities. This awareness also leads to a growing sense of self (identity and agency) and the development of romantic relationships. The specific modern tendency of a female protagonist as leader in the rebellion against state and state apparatus, who gains in agency and independence in this rebellion, an important part of the identification with and construction of gender, while being part of the traditional coming-of-age young adult novel will be emphasized. A comparison between the traditional themes, structures and plots of young adult literature (YAL) with adult dystopian literature and those of recent dystopian YAL will be made while the hybrid nature of this genre and the 'sense of unease' but also of hope, as an essential part of youth literature, in the closure to these novels will be discussed. Important questions about the role of the didactic nature of these texts and the political issues and the importance of the formation of agency and identity for the young adult reader, as well as identification with the protagonists in this genre, are also part of this discussion of The Mark and other YAL novels.

Keywords: agency, dystopian literature, gender construction, young adult literature

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431 Perceived Procedural Justice and Organizational Citizenship Behavior: Evidence from a Security Organization

Authors: Noa Nelson, Orit Appel, Rachel Ben-ari

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Organizational Citizenship Behavior (OCB) is voluntary employee behavior that contributes to the organization beyond formal job requirements. It can take different forms, such as helping teammates (OCB toward individuals; hence, OCB-I), or staying after hours to attend a task force (OCB toward the organization; hence, OCB-O). Generally, OCB contributes substantially to organizational climate, goals, productivity, and resilience, so organizations need to understand what encourages it. This is particularly challenging in security organizations. Security work is characterized by high levels of stress and burnout, which is detrimental to OCB, and security organizational design emphasizes formal rules and clear hierarchies, leaving employees with less freedom for voluntary behavior. The current research explored the role of Perceived Procedural Justice (PPJ) in enhancing OCB in a security organization. PPJ refers to how fair decision-making processes are perceived to be. It involves the sense that decision makers are objective, attentive to everyone's interests, respectful in their communications and participatory - allowing individuals a voice in decision processes. Justice perceptions affect motivation, and it was specifically suggested that PPJ creates an attachment to one's organization and personal interest in its success. Accordingly, PPJ had been associated with OCB, but hardly any research tested their association with security organizations. The current research was conducted among prison guards in the Israel Prison Service, to test a correlational and a causal association between PPJ and OCB. It differentiated between perceptions of direct commander procedural justice (CPJ), and perceptions of organization procedural justice (OPJ), hypothesizing that CPJ would relate to OCB-I, while OPJ would relate to OCB-O. In the first study, 336 prison guards (305 male) from 10 different prisons responded to questionnaires measuring their own CPJ, OPJ, OCB-I, and OCB-O. Hierarchical linear regression analyses indicated the significance of commander procedural justice (CPJ): It associated with OCB-I and also associated with OPJ, which, in turn, associated with OCB-O. The second study tested CPJ's causal effects on prison guards' OCB-I and OCB-O; 311 prison guards (275 male) from 14 different prisons read scenarios that described either high or low CPJ, and then evaluated the likelihood of that commander's prison guards performing OCB-I and OCB-O. In this study, CPJ enhanced OCB-O directly. It also contributed to OCB-I, indirectly: CPJ enhanced the motivation for collaboration with the commander, which respondents also evaluated after reading scenarios. Collaboration, in turn, associated with OCB-I. The studies demonstrate that procedural justice, especially commander's PJ, promotes OCB in security work environments. This is important because extraordinary teamwork and motivation are needed to deal with emergency situations and with delicate security challenges. Following the studies, the Israel Prison Service implemented personal procedural justice training for commanders and unit level programs for procedurally just decision processes. From a theoretical perspective, the studies extend the knowledge on PPJ and OCB to security work environments and contribute evidence on PPJ's causal effects. They also call for further research, to understand the mechanisms through which different types of PPJ affect different types of OCB.

Keywords: organizational citizenship behavior, perceived procedural justice, prison guards, security organizations

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430 An Emergentist Defense of Incompatibility between Morally Significant Freedom and Causal Determinism

Authors: Lubos Rojka

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The common perception of morally responsible behavior is that it presupposes freedom of choice, and that free decisions and actions are not determined by natural events, but by a person. In other words, the moral agent has the ability and the possibility of doing otherwise when making morally responsible decisions, and natural causal determinism cannot fully account for morally significant freedom. The incompatibility between a person’s morally significant freedom and causal determinism appears to be a natural position. Nevertheless, some of the most influential philosophical theories on moral responsibility are compatibilist or semi-compatibilist, and they exclude the requirement of alternative possibilities, which contradicts the claims of classical incompatibilism. The compatibilists often employ Frankfurt-style thought experiments to prove their theory. The goal of this paper is to examine the role of imaginary Frankfurt-style examples in compatibilist accounts. More specifically, the compatibilist accounts defended by John Martin Fischer and Michael McKenna will be inserted into the broader understanding of a person elaborated by Harry Frankfurt, Robert Kane and Walter Glannon. Deeper analysis reveals that the exclusion of alternative possibilities based on Frankfurt-style examples is problematic and misleading. A more comprehensive account of moral responsibility and morally significant (source) freedom requires higher order complex theories of human will and consciousness, in which rational and self-creative abilities and a real possibility to choose otherwise, at least on some occasions during a lifetime, are necessary. Theoretical moral reasons and their logical relations seem to require a sort of higher-order agent-causal incompatibilism. The ability of theoretical or abstract moral reasoning requires complex (strongly emergent) mental and conscious properties, among which an effective free will, together with first and second-order desires. Such a hierarchical theoretical model unifies reasons-responsiveness, mesh theory and emergentism. It is incompatible with physical causal determinism, because such determinism only allows non-systematic processes that may be hard to predict, but not complex (strongly) emergent systems. An agent’s effective will and conscious reflectivity is the starting point of a morally responsible action, which explains why a decision is 'up to the subject'. A free decision does not always have a complete causal history. This kind of an emergentist source hyper-incompatibilism seems to be the best direction of the search for an adequate explanation of moral responsibility in the traditional (merit-based) sense. Physical causal determinism as a universal theory would exclude morally significant freedom and responsibility in the traditional sense because it would exclude the emergence of and supervenience by the essential complex properties of human consciousness.

Keywords: consciousness, free will, determinism, emergence, moral responsibility

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429 Deep Learning Approach for Colorectal Cancer’s Automatic Tumor Grading on Whole Slide Images

Authors: Shenlun Chen, Leonard Wee

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Tumor grading is an essential reference for colorectal cancer (CRC) staging and survival prognostication. The widely used World Health Organization (WHO) grading system defines histological grade of CRC adenocarcinoma based on the density of glandular formation on whole slide images (WSI). Tumors are classified as well-, moderately-, poorly- or un-differentiated depending on the percentage of the tumor that is gland forming; >95%, 50-95%, 5-50% and <5%, respectively. However, manually grading WSIs is a time-consuming process and can cause observer error due to subjective judgment and unnoticed regions. Furthermore, pathologists’ grading is usually coarse while a finer and continuous differentiation grade may help to stratifying CRC patients better. In this study, a deep learning based automatic differentiation grading algorithm was developed and evaluated by survival analysis. Firstly, a gland segmentation model was developed for segmenting gland structures. Gland regions of WSIs were delineated and used for differentiation annotating. Tumor regions were annotated by experienced pathologists into high-, medium-, low-differentiation and normal tissue, which correspond to tumor with clear-, unclear-, no-gland structure and non-tumor, respectively. Then a differentiation prediction model was developed on these human annotations. Finally, all enrolled WSIs were processed by gland segmentation model and differentiation prediction model. The differentiation grade can be calculated by deep learning models’ prediction of tumor regions and tumor differentiation status according to WHO’s defines. If multiple WSIs were possessed by a patient, the highest differentiation grade was chosen. Additionally, the differentiation grade was normalized into scale between 0 to 1. The Cancer Genome Atlas, project COAD (TCGA-COAD) project was enrolled into this study. For the gland segmentation model, receiver operating characteristic (ROC) reached 0.981 and accuracy reached 0.932 in validation set. For the differentiation prediction model, ROC reached 0.983, 0.963, 0.963, 0.981 and accuracy reached 0.880, 0.923, 0.668, 0.881 for groups of low-, medium-, high-differentiation and normal tissue in validation set. Four hundred and one patients were selected after removing WSIs without gland regions and patients without follow up data. The concordance index reached to 0.609. Optimized cut off point of 51% was found by “Maxstat” method which was almost the same as WHO system’s cut off point of 50%. Both WHO system’s cut off point and optimized cut off point performed impressively in Kaplan-Meier curves and both p value of logrank test were below 0.005. In this study, gland structure of WSIs and differentiation status of tumor regions were proven to be predictable through deep leaning method. A finer and continuous differentiation grade can also be automatically calculated through above models. The differentiation grade was proven to stratify CAC patients well in survival analysis, whose optimized cut off point was almost the same as WHO tumor grading system. The tool of automatically calculating differentiation grade may show potential in field of therapy decision making and personalized treatment.

Keywords: colorectal cancer, differentiation, survival analysis, tumor grading

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428 Exploratory Study on Mediating Role of Commitment-to-Change in Relations between Employee Voice, Employee Involvement and Organizational Change Readiness

Authors: Rohini Sharma, Chandan Kumar Sahoo, Rama Krishna Gupta Potnuru

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Strong competitive forces and requirements to achieve efficiency are forcing the organizations to realize the necessity and inevitability of change. What's more, the trend does not appear to be abating. Researchers have estimated that about two thirds of change project fails. Empirical evidences further shows that organizations invest significantly in the planned change but people side is accounted for in a token or instrumental way, which is identified as one of the important reason, why change endeavours fail. However, whatever be the reason for change, organizational change readiness must be gauged prior to the institutionalization of organizational change. Hence, in this study the influence of employee voice and employee involvement on organizational change readiness via commitment-to-change is examined, as it is an area yet to be extensively studied. Also, though a recent study has investigated the interrelationship between leadership, organizational change readiness and commitment to change, our study further examined these constructs in relation with employee voice and employee involvement that plays a consequential role for organizational change readiness. Further, integrated conceptual model weaving varied concepts relating to organizational readiness with focus on commitment to change as mediator was found to be an area, which required more theorizing and empirical validation, and this study rooted in an Indian public sector organization is a step in this direction. Data for the study were collected through a survey among employees of Rourkela Steel Plant (RSP), a unit of Steel Authority of India Limited (SAIL); the first integrated Steel Plant in the public sector in India, for which stratified random sampling method was adopted. The schedule was distributed to around 700 employees, out of which 516 complete responses were obtained. The pre-validated scales were used for the study. All the variables in the study were measured on a five-point Likert scale ranging from “strongly disagree (1)” to “strongly agree (5)”. Structural equation modeling (SEM) using AMOS 22 was used to examine the hypothesized model, which offers a simultaneous test of an entire system of variables in a model. The study results shows that inter-relationship between employee voice and commitment-to-change, employee involvement and commitment-to-change and commitment-to-change and organizational change readiness were significant. To test the mediation hypotheses, Baron and Kenny’s technique was used. Examination of direct and mediated effect of mediators confirmed that commitment-to-change partially mediated the relation between employee involvement and organizational change readiness. Furthermore, study results also affirmed that commitment-to-change does not mediate the relation between employee involvement and organizational change readiness. The empirical exploration therefore establishes that it is important to harness employee’s valuable suggestions regarding change for building organizational change readiness. Regarding employee involvement, it was found that sharing information and involving people in decision-making, leads to a creation of participative climate, which educes employee commitment during change and commitment-to-change further, fosters organizational change readiness.

Keywords: commitment-to-change, change management, employee voice, employee involvement, organizational change readiness

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427 Language Education Policy in Arab Schools in Israel

Authors: Fatin Mansour Daas

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Language education responds to and is reflective of emerging social and political trends. Language policies and practices are shaped by political, economic, social and cultural considerations. Following this, Israeli language education policy as implemented in Arab schools in Israel is influenced by the particular political and social situation of Arab-Palestinian citizens of Israel. This national group remained in their homeland following the war in 1948 between Israel and its Arab neighbors and became Israeli citizens following the establishment of the State of Israel. This study examines language policy in Arab schools in Israel from 1948 until the present time in light of the unique experience of the Palestinian Arab homeland minority in Israel with a particular focus on questions of politics and identity. The establishment of the State of Israel triggered far-reaching political, social and educational transformations within Arab Palestinian society in Israel, including in the area of language and language studies. Since 1948, the linguistic repertoire of Palestinian Arabs in Israel has become more complex and diverse, while the place and status of different languages have changed. Following the establishment of the State of Israel, only Hebrew and Arabic were retained as the official languages, and Israeli policy reflected this in schools as well: with the advent of the Jewish state, Hebrew language education among Palestinians in Israel has increased. Similarly, in Arab Palestinian schools in Israel, English is taught as a third language, Hebrew as a second language, and Arabic as a first language – even though it has become less important to native Arabic speakers. This research focuses on language studies and language policy in the Arab school system in Israel from 1948 onwards. It will analyze the relative focus of language education between the different languages, the rationale of various language education policies, and the pedagogic approach used to teach each language and student achievements vis-à-vis language skills. This study seeks to understand the extent to which Arab schools in Israel are multi-lingual by examining successes, challenges and difficulties in acquiring the respective languages. This qualitative study will analyze five different components of language education policy: (1) curriculum, (2) learning materials; (3) assessment; (4) interviews and (5) archives. Firstly, it consists of an analysis examining language education curricula, learning materials and assessments used in Arab schools in Israel from 1948-2018 including a selection of language textbooks for the compulsory years of study and the final matriculation (Bagrut) examinations. The findings will also be based on archival material which traces the evolution of language education policy in Arabic schools in Israel from the years 1948-2018. This archival research, furthermore, will reveal power relations and general decision-making in the field of the Arabic education system in Israel. The research will also include interviews with Ministry of Education staff who provide instructional oversight in the instruction of the three languages in the Arabic education system in Israel. These interviews will shed light on the goals of language education as understood by those who are in charge of implementing policy.

Keywords: language education policy, languages, multilingualism, language education, educational policy, identity, Palestinian-Arabs, Arabs in Israel, educational school system

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426 Strength Performance and Microstructure Characteristics of Natural Bonded Fiber Composites from Malaysian Bamboo

Authors: Shahril Anuar Bahari, Mohd Azrie Mohd Kepli, Mohd Ariff Jamaludin, Kamarulzaman Nordin, Mohamad Jani Saad

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Formaldehyde release from wood-based panel composites can be very toxicity and may increase the risk of human health as well as environmental problems. A new bio-composites product without synthetic adhesive or resin is possible to be developed in order to reduce these problems. Apart from formaldehyde release, adhesive is also considered to be expensive, especially in the manufacturing of composite products. Natural bonded composites can be termed as a panel product composed with any type of cellulosic materials without the addition of synthetic resins. It is composed with chemical content activation in the cellulosic materials. Pulp and paper making method (chemical pulping) was used as a general guide in the composites manufacturing. This method will also generally reduce the manufacturing cost and the risk of formaldehyde emission and has potential to be used as an alternative technology in fiber composites industries. In this study, the natural bonded bamboo fiber composite was produced from virgin Malaysian bamboo fiber (Bambusa vulgaris). The bamboo culms were chipped and digested into fiber using this pulping method. The black liquor collected from the pulping process was used as a natural binding agent in the composition. Then the fibers were mixed and blended with black liquor without any resin addition. The amount of black liquor used per composite board was 20%, with approximately 37% solid content. The composites were fabricated using a hot press machine at two different board densities, 850 and 950 kg/m³, with two sets of hot pressing time, 25 and 35 minutes. Samples of the composites from different densities and hot pressing times were tested in flexural strength and internal bonding (IB) for strength performance according to British Standard. Modulus of elasticity (MOE) and modulus of rupture (MOR) was determined in flexural test, while tensile force perpendicular to the surface was recorded in IB test. Results show that the strength performance of the composites with 850 kg/m³ density were significantly higher than 950 kg/m³ density, especially for samples from 25 minutes hot pressing time. Strength performance of composites from 25 minutes hot pressing time were generally greater than 35 minutes. Results show that the maximum mean values of strength performance were recorded from composites with 850 kg/m³ density and 25 minutes pressing time. The maximum mean values for MOE, MOR and IB were 3251.84, 16.88 and 0.27 MPa, respectively. Only MOE result has conformed to high density fiberboard (HDF) standard (2700 MPa) in British Standard for Fiberboard Specification, BS EN 622-5: 2006. Microstructure characteristics of composites can also be related to the strength performance of the composites, in which, the observed fiber damage in composites from 950 kg/m³ density and overheat of black liquor led to the low strength properties, especially in IB test.

Keywords: bamboo fiber, natural bonded, black liquor, mechanical tests, microstructure observations

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425 Nurturing Students' Creativity through Engagement in Problem Posing and Self-Assessment of Its Development

Authors: Atara Shriki, Ilana Lavy

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In a rapidly changing technological society, creativity is considered as an engine of economic and social progress. No doubt the education system has a central role in nurturing all students’ creativity, however, it is normally not encouraged at school. The causes of this reality are related to a variety of circumstances, among them: external pressures to cover the curriculum and succeed in standardized tests that mostly require algorithmic thinking and implementation of rules; teachers’ tendency to teach similarly to the way they themselves were taught as school students; relating creativity to giftedness, and therefore avoid nurturing all students' creativity; lack of adequate learning materials and accessible tools for following and evaluating the development of students’ creativity; and more. Since success in academic studies requires, among other things, creativity, lecturers in higher education institutions should consider appropriate ways to nurture students’ creative thinking and assess its development. Obviously, creativity has a multifaceted nature, numerous definitions, various perspectives for studying its essence (e.g., process, personality, environment, and product), and several approaches aimed at evaluating and assessing creative expressions (e.g., cognitive, social-personal, and psychometric). In this framework, we suggest nurturing students’ creativity through engaging them in problem posing activities that are part of inquiry assignments. In order to assess the development of their creativity, we propose to employ a model that was designed for this purpose, based on the psychometric approach, viewing the posed problems as the “creative product”. The model considers four measurable aspects- fluency, flexibility, originality, and organization, as well as a total score of creativity that reflects the relative weights of each aspect. The scores given to learners are of two types: (1) Total scores- the absolute number of posed problems with respect to each of the four aspects, and a final score of creativity; (2) Relative scores- each absolute number is transformed into a number that relates to the relative infrequency of the posed problems in student’s reference group. Through converting the scores received over time into a graphical display, students can assess their progress both with respect to themselves and relative to their reference group. Course lecturers can get a picture of the strengths and weaknesses of each student as well as the class as a whole, and to track changes that occur over time in response to the learning environment they had generated. Such tracking may assist lecturers in making pedagogical decisions about emphases that should be put on one or more aspects of creativity, and about the students that should be given a special attention. Our experience indicates that schoolteachers and lecturers in higher education institutes find the combination of engaging learners in problem posing along with self-assessment of their progress through utilizing the graphical display of accumulating total and relative scores has the potential to realize most learners’ creative potential.

Keywords: creativity, problem posing, psychometric model, self-assessment

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424 Constraints to Partnership Based Financing in Islamic Banks: A Systematic Review of Literature

Authors: Muhammad Nouman, Salim Gul, Karim Ullah

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Partnership has been understood as the essence of Islamic banking. However, in practice, the non-partnership paradigm dominates the operations of Islamic banks. Islamic banks adopt partnership contracts for the scheme of deposits, especially for term deposit accounts. However, they do not adopt partnership contracts (i.e., Musharakah and Mudarabah) as the main financing scheme. In practice, non-partnership contracts including Murabahah and Ijara are widely used for financing. Many authors have provided different explanations for the less utilization of the partnership contracts as a scheme of financing. However, the typology of constraints remains missing. The extant literature remains scattered, with diverse studies focused on different dimensions of the issue. Therefore, there is no unified understanding of the constraints in the application of the partnership contracts. This paper aims to highlight the major factors hindering the application of partnership contracts, and produce a coherent view by synthesizing different explanations provided in several studies conducted around the globe. The present study employs insights form the extant literature using a systematic review and provides academia, practitioners, and policy makers with a holistic framework to name and make sense of what is making partnership contracts a less attractive option for Islamic banks. A total of 84 relevant publications including 11 books, 14 chapters of edited books, 48 journal articles, 8 conference papers and 3 IMF working papers were selected using a systematic procedure. Analysis of these selected publications followed three steps: i) In the first step of analysis the constraints explicitly appearing in the literature set of 84 articles were extracted, ii) In the second step 27 factors hindering the application of partnership contracts were identified from the constraints extracted in the first step with the overlapping items either eliminated or combined, iii) In the last step the factors identified in the second step were classified into three distinct categories. Our intention was to develop the typology of constraints by connecting the rather abstract concepts into the broader sets of constraints for better conceptualization and policy implications. Our framework highlights that there are mainly three facets of lower preference for partnership contracts of financing. First, there are several factors in the contemporary business settings, prevailing social setting, and the bank’s internal environment that underpin uncertainty in the success of partnership contracts of financing. Second, partnership contracts have lower demand i.e., entrepreneurs prefer to use non-partnership contracts for financing their ventures due to the inherent restraining characteristics of the partnership contracts. Finally, there are certain factors in the regulatory framework that restraint the extensive utilization of partnership contracts of financing by Islamic banks. The present study contributes to the Islamic banking literature in many ways. It provides clarification to the heavily criticized operations of Islamic banks, integrates the scattered literature, and provides a holistic framework for better conceptualization of the key constraints in the application of the partnership contracts and policy implications. Moreover, it demonstrates an application of systematic review in Islamic banking research.

Keywords: Islamic banking, Islamic finance, Mudarabah, Musharakah, partnership, systematic review

Procedia PDF Downloads 244
423 Research Project on Learning Rationality in Strategic Behaviors: Interdisciplinary Educational Activities in Italian High Schools

Authors: Giovanna Bimonte, Luigi Senatore, Francesco Saverio Tortoriello, Ilaria Veronesi

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The education process considers capabilities not only to be seen as a means to a certain end but rather as an effective purpose. Sen's capability approach challenges human capital theory, which sees education as an ordinary investment undertaken by individuals. A complex reality requires complex thinking capable of interpreting the dynamics of society's changes to be able to make decisions that can be rational for private, ethical and social contexts. Education is not something removed from the cultural and social context; it exists and is structured within it. In Italy, the "Mathematical High School Project" is a didactic research project is based on additional laboratory courses in extracurricular hours where mathematics intends to bring itself in a dialectical relationship with other disciplines as a cultural bridge between the two cultures, the humanistic and the scientific ones, with interdisciplinary educational modules on themes of strong impact in younger life. This interdisciplinary mathematics presents topics related to the most advanced technologies and contemporary socio-economic frameworks to demonstrate how mathematics is not only a key to reading but also a key to resolving complex problems. The recent developments in mathematics provide the potential for profound and highly beneficial changes in mathematics education at all levels, such as in socio-economic decisions. The research project is built to investigate whether repeated interactions can successfully promote cooperation among students as rational choice and if the skill, the context and the school background can influence the strategies choice and the rationality. A Laboratory on Game Theory as mathematical theory was conducted in the 4th year of the Mathematical High Schools and in an ordinary scientific high school of the Scientific degree program. Students played two simultaneous games of repeated Prisoner's Dilemma with an indefinite horizon, with two different competitors in each round; even though the competitors in each round will remain the same for the duration of the game. The results highlight that most of the students in the two classes used the two games with an immunization strategy against the risk of losing: in one of the games, they started by playing Cooperate, and in the other by the strategy of Compete. In the literature, theoretical models and experiments show that in the case of repeated interactions with the same adversary, the optimal cooperation strategy can be achieved by tit-for-tat mechanisms. In higher education, individual capacities cannot be examined independently, as conceptual framework presupposes a social construction of individuals interacting and competing, making individual and collective choices. The paper will outline all the results of the experimentation and the future development of the research.

Keywords: game theory, interdisciplinarity, mathematics education, mathematical high school

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422 Empowering Leaders: Strategies for Effective Management in a Changing World

Authors: Shahid Ali

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Leadership and management are essential components of running successful organizations. Both concepts are closely related but serve different purposes in the overall management of a company. Leadership focuses on inspiring and motivating employees towards a common goal, while management involves coordinating and directing resources to achieve organizational objectives efficiently. Objectives of Leadership and Management: Inspiring and motivating employees: A key objective of leadership is to inspire and motivate employees to work towards achieving the organization’s goals. Effective leaders create a vision that employees can align with and provide the necessary motivation to drive performance. Setting goals and objectives: Both leadership and management play a crucial role in setting goals and objectives for the organization. Leaders create a vision for the future, while managers develop plans to achieve specific objectives within the given timeframe. Implementing strategies: Leaders come up with innovative strategies to drive the organization forward, while managers are responsible for implementing these strategies effectively. Together, leadership and management ensure that the organization’s plans are executed efficiently. Contributions of Leadership and Management: Employee Engagement: Effective leadership and management can increase employee engagement and satisfaction. When employees feel motivated and inspired by their leaders, they are more likely to be engaged in their work and contribute to the organization’s success. Organizational Success: Good leadership and management are essential for navigating the challenges and changes that organizations face. By setting clear goals, inspiring employees, and making strategic decisions, leaders and managers can drive organizational success. Talent Development: Leaders and managers are responsible for identifying and developing talent within the organization. By providing feedback, training, and coaching, they can help employees reach their full potential and contribute effectively to the organization. Research Type: The research on leadership and management is typically quantitative and qualitative in nature. Quantitative research involves the collection and analysis of numerical data to understand the impact of leadership and management practices on organizational outcomes. This type of research often uses surveys, questionnaires, and statistical analysis to measure variables such as employee satisfaction, performance, and organizational success. Qualitative research, on the other hand, involves exploring the subjective experiences and perspectives of individuals related to leadership and management. This type of research may include interviews, observations, and case studies to gain a deeper understanding of how leadership and management practices influence organizational behavior and outcomes. In conclusion, leadership and management play a critical role in the success of organizations. Through effective leadership and management practices, organizations can inspire and motivate employees, set goals, and implement strategies to achieve their objectives. Research on leadership and management helps to understand the impact of these practices on organizational outcomes and provides valuable insights for improving leadership and management practices in the future.

Keywords: empowering, leadership, management, adaptability

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421 Contraceptive Uptake among Women in Low Socio-Economic Areas in Kenya: Quantitative Analysis of Secondary Data

Authors: J. Waita, S. Wamuhu, J. Makoyo, M. Rachel, T. Ngangari, W. Christine, M. Zipporah

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Contraceptive use is one of the key global strategies to alleviate maternal mortality. Global efforts through advocating for contraceptive uptake and service provision has led improved contraceptive prevalence. In Kenya maternal mortality rate has remained a challenged despites efforts by government and non-governmental organizations. Objective: To describe the uptake of contraceptives among women in Tunza Clinics, Kenya. Design and Methods: Ps Kenya through health care marketing fund is implementing a family planning program among its 350 Tunza fractional franchise facilities. Through private partnership, private owned facilities in low socio-economic areas are recruited and trained on contraceptive technology update. The providers are supported through facilitative supervision through a mobile based application Health Network Quality Improvement System (HNQIS) and interpersonal communication through 150 community based volunteers. The data analyzed in this paper was collected between January to July 2017 to show the uptake of modern Contraceptives among women in the Tunza franchise, method mix, age and distribution among the age bracket. Further analysis compares two different service delivery strategies; outreach and walk ins. Supportive supervision HNQIS scores was analyzed. Results: During the time period, a total of 132121 family planning clients were attended in 350 facilities. The average age of clients was 29.6 years. The average number of clients attended in the facilities per month was 18874. 73.7 %( n=132121) of the clients attended in the Tunza facilities were aged above 25 years while 22.1% 20-24 years and 4.2% 15-19 years. On contraceptive method mix, intra uterine device insertions clients contributed to 7.5%, implant insertions 15.3%, pills 11.2%, injections 62.7% while condoms and emergency pills had 2.7% and 0.6% respectively. Analysis of service delivery strategy indicated more than 79% of the clients were walk ins while 21% were attended to during outreaches. Uptake of long term contraceptive methods during outreaches was 73% of the clients while short term modern methods were 27%. Health Network Quality Improvement system assessment scores indicated 51% of the facilities scored over 90%, 25% scoring 80-89% while 21% scored below 80%. Conclusion: Preference for short term methods by women is possibly associated to cost as they are cheaper and easy to administer. When the cost of intra uterine device Implants is meant affordable during outreaches, the uptake is observed to increase. Making intra uterine device and implants affordable to women is a key strategy in increasing contraceptive prevalence hence averting maternal mortality.

Keywords: contraceptives, contraceptive uptake, low socio economic, supportive supervision

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420 Improving Patient Outcomes for Aspiration Pneumonia

Authors: Mary Farrell, Maria Soubra, Sandra Vega, Dorothy Kakraba, Joanne Fontanilla, Moira Kendra, Danielle Tonzola, Stephanie Chiu

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Pneumonia is the most common infectious cause of hospitalizations in the United States, with more than one million admissions annually and costs of $10 billion every year, making it the 8th leading cause of death. Aspiration pneumonia is an aggressive type of pneumonia that results from inhalation of oropharyngeal secretions and/or gastric contents and is preventable. The authors hypothesized that an evidence-based aspiration pneumonia clinical care pathway could reduce 30-day hospital readmissions and mortality rates, while improving the overall care of patients. We conducted a retrospective chart review on 979 patients discharged with aspiration pneumonia from January 2021 to December 2022 at Overlook Medical Center. The authors identified patients who were coded with aspiration pneumonia and/or stable sepsis. Secondarily, we identified 30-day readmission rates for aspiration pneumonia from a SNF. The Aspiration Pneumonia Clinical Care Pathway starts in the emergency department (ED) with the initiation of antimicrobials within 4 hours of admission and early recognition of aspiration. Once this is identified, a swallow test is initiated by the bedside nurse, and if the patient demonstrates dysphagia, they are maintained on strict nothing by mouth (NPO) followed by a speech and language pathologist (SLP) referral for an appropriate modified diet recommendation. Aspiration prevention techniques included the avoidance of straws, 45-degree positioning, no talking during meals, taking small bites, placement of the aspiration wrist band, and consuming meals out of the bed in a chair. Nursing education was conducted with a newly created online learning module about aspiration pneumonia. The authors identified 979 patients, with an average age of 73.5 years old, who were diagnosed with aspiration pneumonia on the index hospitalization. These patients were reviewed for a 30-day readmission for aspiration pneumonia or stable sepsis, and mortality rates from January 2021 to December 2022 at Overlook Medical Center (OMC). The 30-day readmission rates were significantly lower in the cohort that received the clinical care pathway (35.0% vs. 27.5%, p = 0.011). When evaluating the mortality rates in the pre and post intervention cohort the authors discovered the mortality rates were lower in the post intervention cohort (23.7% vs 22.4%, p = 0.61) Mortality among non-white (self-reported as non-white) patients were lower in the post intervention cohort (34.4% vs. 21.0% , p = 0.05). Patients who reported as a current smoker/vaper in the pre and post cohorts had increased mortality rates (5.9% vs 22%). There was a decrease in mortality for the male population but an increase in mortality for women in the pre and post cohorts (19% vs. 25%). The authors attributed this increase in mortality in the post intervention cohort to more active smokers, more former smokers, and more being admitted from a SNF. This research identified that implementation of an Aspiration Pneumonia Clinical Care Pathway showed a statistically significant decrease in readmission rates and mortality rates in non-whites. The 30-day readmission rates were lower in the cohort that received the clinical care pathway (35.0% vs. 27.5%, p = 0.011).

Keywords: aspiration pneumonia, mortality, quality improvement, 30-day pneumonia readmissions

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419 The Effectiveness of an Occupational Therapy Metacognitive-Functional Intervention for the Improvement of Human Risk Factors of Bus Drivers

Authors: Navah Z. Ratzon, Rachel Shichrur

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Background: Many studies have assessed and identified the risk factors of safe driving, but there is relatively little research-based evidence concerning the ability to improve the driving skills of drivers in general and in particular of bus drivers, who are defined as a population at risk. Accidents involving bus drivers can endanger dozens of passengers and cause high direct and indirect damages. Objective: To examine the effectiveness of a metacognitive-functional intervention program for the reduction of risk factors among professional drivers relative to a control group. Methods: The study examined 77 bus drivers working for a large public company in the center of the country, aged 27-69. Twenty-one drivers continued to the intervention stage; four of them dropped out before the end of the intervention. The intervention program we developed was based on previous driving models and the guiding occupational therapy practice framework model in Israel, while adjusting the model to the professional driving in public transportation and its particular risk factors. Treatment focused on raising awareness to safe driving risk factors identified at prescreening (ergonomic, perceptual-cognitive and on-road driving data), with reference to the difficulties that the driver raises and providing coping strategies. The intervention has been customized for each driver and included three sessions of two hours. The effectiveness of the intervention was tested using objective measures: In-Vehicle Data Recorders (IVDR) for monitoring natural driving data, traffic accident data before and after the intervention, and subjective measures (occupational performance questionnaire for bus drivers). Results: Statistical analysis found a significant difference between the degree of change in the rate of IVDR perilous events (t(17)=2.14, p=0.046), before and after the intervention. There was significant difference in the number of accidents per year before and after the intervention in the intervention group (t(17)=2.11, p=0.05), but no significant change in the control group. Subjective ratings of the level of performance and of satisfaction with performance improved in all areas tested following the intervention. The change in the ‘human factors/person’ field, was significant (performance : t=- 2.30, p=0.04; satisfaction with performance : t=-3.18, p=0.009). The change in the ‘driving occupation/tasks’ field, was not significant but showed a tendency toward significance (t=-1.94, p=0.07,). No significant differences were found in driving environment-related variables. Conclusions: The metacognitive-functional intervention significantly improved the objective and subjective measures of safety of bus drivers’ driving. These novel results highlight the potential contribution of occupational therapists, using metacognitive functional treatment, to preventing car accidents among the healthy drivers population and improving the well-being of these drivers. This study also enables familiarity with advanced technologies of IVDR systems and enriches the knowledge of occupational therapists in regards to using a wide variety of driving assessment tools and making the best practice decisions.

Keywords: bus drivers, IVDR, human risk factors, metacognitive-functional intervention

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418 An Overview of Bioinformatics Methods to Detect Novel Riboswitches Highlighting the Importance of Structure Consideration

Authors: Danny Barash

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Riboswitches are RNA genetic control elements that were originally discovered in bacteria and provide a unique mechanism of gene regulation. They work without the participation of proteins and are believed to represent ancient regulatory systems in the evolutionary timescale. One of the biggest challenges in riboswitch research is that many are found in prokaryotes but only a small percentage of known riboswitches have been found in certain eukaryotic organisms. The few examples of eukaryotic riboswitches were identified using sequence-based bioinformatics search methods that include some slight structural considerations. These pattern-matching methods were the first ones to be applied for the purpose of riboswitch detection and they can also be programmed very efficiently using a data structure called affix arrays, making them suitable for genome-wide searches of riboswitch patterns. However, they are limited by their ability to detect harder to find riboswitches that deviate from the known patterns. Several methods have been developed since then to tackle this problem. The most commonly used by practitioners is Infernal that relies on Hidden Markov Models (HMMs) and Covariance Models (CMs). Profile Hidden Markov Models were also carried out in the pHMM Riboswitch Scanner web application, independently from Infernal. Other computational approaches that have been developed include RMDetect by the use of 3D structural modules and RNAbor that utilizes Boltzmann probability of structural neighbors. We have tried to incorporate more sophisticated secondary structure considerations based on RNA folding prediction using several strategies. The first idea was to utilize window-based methods in conjunction with folding predictions by energy minimization. The moving window approach is heavily geared towards secondary structure consideration relative to sequence that is treated as a constraint. However, the method cannot be used genome-wide due to its high cost because each folding prediction by energy minimization in the moving window is computationally expensive, enabling to scan only at the vicinity of genes of interest. The second idea was to remedy the inefficiency of the previous approach by constructing a pipeline that consists of inverse RNA folding considering RNA secondary structure, followed by a BLAST search that is sequence-based and highly efficient. This approach, which relies on inverse RNA folding in general and our own in-house fragment-based inverse RNA folding program called RNAfbinv in particular, shows capability to find attractive candidates that are missed by Infernal and other standard methods being used for riboswitch detection. We demonstrate attractive candidates found by both the moving-window approach and the inverse RNA folding approach performed together with BLAST. We conclude that structure-based methods like the two strategies outlined above hold considerable promise in detecting riboswitches and other conserved RNAs of functional importance in a variety of organisms.

Keywords: riboswitches, RNA folding prediction, RNA structure, structure-based methods

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417 Two-Dimensional Dynamics Motion Simulations of F1 Rare Wing-Flap

Authors: Chaitanya H. Acharya, Pavan Kumar P., Gopalakrishna Narayana

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In the realm of aerodynamics, numerous vehicles incorporate moving components to enhance their performance. For instance, airliners deploy hydraulically operated flaps and ailerons during take-off and landing, while Formula 1 racing cars utilize hydraulic tubes and actuators for various components, including the Drag Reduction System (DRS). The DRS, consisting of a rear wing and adjustable flaps, plays a crucial role in overtaking manoeuvres. The DRS has two positions: the default position with the flaps down, providing high downforce, and the lifted position, which reduces drag, allowing for increased speed and aiding in overtaking. Swift deployment of the DRS during races is essential for overtaking competitors. The fluid flow over the rear wing flap becomes intricate during deployment, involving flow reversal and operational changes, leading to unsteady flow physics that significantly influence aerodynamic characteristics. Understanding the drag and downforce during DRS deployment is crucial for determining race outcomes. While experiments can yield accurate aerodynamic data, they can be expensive and challenging to conduct across varying speeds. Computational Fluid Dynamics (CFD) emerges as a cost-effective solution to predict drag and downforce across a range of speeds, especially with the rapid deployment of the DRS. This study employs the finite volume-based solver Ansys Fluent, incorporating dynamic mesh motions and a turbulent model to capture the complex flow phenomena associated with the moving rear wing flap. A dedicated section for the rare wing-flap is considered in the present simulations, and the aerodynamics of these sections closely resemble S1223 aerofoils. Before delving into the simulations of the rare wing-flap aerofoil, numerical results undergo validation using experimental data from an NLR flap aerofoil case, encompassing different flap angles at two distinct angles of attack was carried out. The increase in flap angle as increase in lift and drag is observed for a given angle of attack. The simulation methodology for the rare-wing-flap aerofoil case involves specific time durations before lifting the flap. During this period, drag and downforce values are determined as 330 N and 1800N, respectively. Following the flap lift, a noteworthy reduction in drag to 55 % and a decrease in downforce to 17 % are observed. This understanding is critical for making instantaneous decisions regarding the deployment of the Drag Reduction System (DRS) at specific speeds, thereby influencing the overall performance of the Formula 1 racing car. Hence, this work emphasizes the utilization of dynamic mesh motion methodology to predict the aerodynamic characteristics during the deployment of the DRS in a Formula 1 racing car.

Keywords: DRS, CFD, drag, downforce, dynamics mesh motion

Procedia PDF Downloads 69
416 Integrating Natural Language Processing (NLP) and Machine Learning in Lung Cancer Diagnosis

Authors: Mehrnaz Mostafavi

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The assessment and categorization of incidental lung nodules present a considerable challenge in healthcare, often necessitating resource-intensive multiple computed tomography (CT) scans for growth confirmation. This research addresses this issue by introducing a distinct computational approach leveraging radiomics and deep-learning methods. However, understanding local services is essential before implementing these advancements. With diverse tracking methods in place, there is a need for efficient and accurate identification approaches, especially in the context of managing lung nodules alongside pre-existing cancer scenarios. This study explores the integration of text-based algorithms in medical data curation, indicating their efficacy in conjunction with machine learning and deep-learning models for identifying lung nodules. Combining medical images with text data has demonstrated superior data retrieval compared to using each modality independently. While deep learning and text analysis show potential in detecting previously missed nodules, challenges persist, such as increased false positives. The presented research introduces a Structured-Query-Language (SQL) algorithm designed for identifying pulmonary nodules in a tertiary cancer center, externally validated at another hospital. Leveraging natural language processing (NLP) and machine learning, the algorithm categorizes lung nodule reports based on sentence features, aiming to facilitate research and assess clinical pathways. The hypothesis posits that the algorithm can accurately identify lung nodule CT scans and predict concerning nodule features using machine-learning classifiers. Through a retrospective observational study spanning a decade, CT scan reports were collected, and an algorithm was developed to extract and classify data. Results underscore the complexity of lung nodule cohorts in cancer centers, emphasizing the importance of careful evaluation before assuming a metastatic origin. The SQL and NLP algorithms demonstrated high accuracy in identifying lung nodule sentences, indicating potential for local service evaluation and research dataset creation. Machine-learning models exhibited strong accuracy in predicting concerning changes in lung nodule scan reports. While limitations include variability in disease group attribution, the potential for correlation rather than causality in clinical findings, and the need for further external validation, the algorithm's accuracy and potential to support clinical decision-making and healthcare automation represent a significant stride in lung nodule management and research.

Keywords: lung cancer diagnosis, structured-query-language (SQL), natural language processing (NLP), machine learning, CT scans

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415 Constitutive Androstane Receptor (CAR) Inhibitor CINPA1 as a Tool to Understand CAR Structure and Function

Authors: Milu T. Cherian, Sergio C. Chai, Morgan A. Casal, Taosheng Chen

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This study aims to use CINPA1, a recently discovered small-molecule inhibitor of the xenobiotic receptor CAR (constitutive androstane receptor) for understanding the binding modes of CAR and to guide CAR-mediated gene expression profiling studies in human primary hepatocytes. CAR and PXR are xenobiotic sensors that respond to drugs and endobiotics by modulating the expression of metabolic genes that enhance detoxification and elimination. Elevated levels of drug metabolizing enzymes and efflux transporters resulting from CAR activation promote the elimination of chemotherapeutic agents leading to reduced therapeutic effectiveness. Multidrug resistance in tumors after chemotherapy could be associated with errant CAR activity, as shown in the case of neuroblastoma. CAR inhibitors used in combination with existing chemotherapeutics could be utilized to attenuate multidrug resistance and resensitize chemo-resistant cancer cells. CAR and PXR have many overlapping modulating ligands as well as many overlapping target genes which confounded attempts to understand and regulate receptor-specific activity. Through a directed screening approach we previously identified a new CAR inhibitor, CINPA1, which is novel in its ability to inhibit CAR function without activating PXR. The cellular mechanisms by which CINPA1 inhibits CAR function were also extensively examined along with its pharmacokinetic properties. CINPA1 binding was shown to change CAR-coregulator interactions as well as modify CAR recruitment at DNA response elements of regulated genes. CINPA1 was shown to be broken down in the liver to form two, mostly inactive, metabolites. The structure-activity differences of CINPA1 and its metabolites were used to guide computational modeling using the CAR-LBD structure. To rationalize how ligand binding may lead to different CAR pharmacology, an analysis of the docked poses of human CAR bound to CITCO (a CAR activator) vs. CINPA1 or the metabolites was conducted. From our modeling, strong hydrogen bonding of CINPA1 with N165 and H203 in the CAR-LBD was predicted. These residues were validated to be important for CINPA1 binding using single amino-acid CAR mutants in a CAR-mediated functional reporter assay. Also predicted were residues making key hydrophobic interactions with CINPA1 but not the inactive metabolites. Some of these hydrophobic amino acids were also identified and additionally, the differential coregulator interactions of these mutants were determined in mammalian two-hybrid systems. CINPA1 represents an excellent starting point for future optimization into highly relevant probe molecules to study the function of the CAR receptor in normal- and pathophysiology, and possible development of therapeutics (for e.g. use for resensitizing chemoresistant neuroblastoma cells).

Keywords: antagonist, chemoresistance, constitutive androstane receptor (CAR), multi-drug resistance, structure activity relationship (SAR), xenobiotic resistance

Procedia PDF Downloads 261