Search results for: evaluation indicators/indices.
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 8350

Search results for: evaluation indicators/indices.

2110 Preparation of Frozen Bivalent Babesial (Babesia Bovis and Babesia Bigemina) Vaccine from Field Isolates and Evaluation of Its Efficacy in Calves

Authors: Muhammad Fiaz Qamar, Ahmad Faraz, Muhammad Arfan Zaman, Kazim Ali, Waleed Akram

Abstract:

Babesiosis is reflected as the most important disease of cattle that are transmitted by arthropods. In Pakistan, its prevalence is up to 29% in the cattle and buffalo population in different regions. Cattle show a long lasting and durable immunity by giving an infection of B.bovis, B. bigemina, or Babesiadivergens. this is used in cattle to immunize them in a few countries as anti-babesiosis vaccine. Development of frozen vaccine allows for complete testing after production of each batch, However, once thawed, its reduced its shelf life, frozen vaccines are more difficult to transport as well as expensive to produce as compared to chilled vaccine. The contamination of blood derived vaccine has the potential risk that makes pre-production and post-production quality control necessary. For the trail master seed production of whole blood frozen bivalent Babesia(Babesiabovis and Babesiabigemina), 100 blood samples of Babesial positive suspected cattle was taken and processed for separation microscopic detection and rectification by PCR. Vaccine passages were done to reduce the parasitaemiasis in live calves. After 8 passages, parasitemia of Babesia reduced from 80% to 15%. Infected donor calf’s blood was taken by jugular cannulation by using preservative free lithium heparin as an anticoagulant (5 International Units IU heparin/ml blood). In lab, parasite containing blood was mixed in equal volumes with 3 M glycerol in PBS supplemented with 5 mM glucose (final concentration of glycerol 1.5 M) at 37°C. The mixture was then equilibrized at 37°C for 30 minutes and were dispensed in required containers (e.g., 5 ml cryovials).

Keywords: distribution, babesia, primer sequences, PCV

Procedia PDF Downloads 84
2109 Microstructure and Hardness Changes on T91 Weld Joint after Heating at 560°C

Authors: Suraya Mohamad Nadzir, Badrol Ahmad, Norlia Berahim

Abstract:

T91 steel has been used as construction material for superheater tubes in sub-critical and super critical boiler. This steel was developed with higher creep strength property as compared to conventional low alloy steel. However, this steel is also susceptible to materials degradation due to its sensitivity to heat treatment especially Post Weld Heat Treatment (PWHT) after weld repair process. Review of PWHT process shows that the holding temperature may different from one batch to other batch of samples depending on the material composition. This issue was reviewed by many researchers and one of the potential solutions is the development of weld repair process without PWHT. This process is possible with the use of temper bead welding technique. However, study has shown the hardness value across the weld joint with exception of PWHT is much higher compare to recommended hardness value. Based on the above findings, a study to evaluate the microstructure and hardness changes of T91 weld joint after heating at 560°C at varying duration was carried out. This study was carried out to evaluate the possibility of self-tempering process during in-service period. In this study, the T91 weld joint was heat-up in air furnace at 560°C for duration of 50 and 150 hours. The heating process was controlled with heating rate of 200°C/hours, and cooling rate about 100°C/hours. Following this process, samples were prepared for the microstructure examination and hardness evaluation. Results have shown full tempered martensite structure and acceptance hardness value was achieved after 50 hours heating. This result shows that the thin component such as T91 superheater tubes is able to self-tempering during service hour.

Keywords: T91, weld-joint, tempered martensite, self-tempering

Procedia PDF Downloads 356
2108 A Fuzzy Hybrıd Decısıon Support System for Naval Base Place Selectıon in a Foreıgn Country

Authors: Latif Yanar, Muharrem Kaçan

Abstract:

In this study, an Analytic Hierarchy Process and Analytic Network Process Decision Support System (DSS) model for determination of a navy base place in another country is proposed together with a decision support software (DESTEC 1.0) developed using C Sharp programming language. The proposed software also has the ability of performing the fuzzy models (Fuzzy AHP and Fuzzy ANP) of the proposed DSS to cope with the ambiguous and linguistic nature of the model. The AHP and ANP model, for a decision support for selecting the best place among the alternatives, including the criteria and alternatives, is developed and solved by the experts from Turkish Navy and Turkish academicians related to international relations branches of the universities in Turkey. Also, the questionnaires used for weighting of the criteria and the alternatives are filled by these experts.Some of our alternatives are: economic and political stability of the third country, the effect of another super power in that country, historical relations, security in that country, social facilities in the city in which the base will be built, the transportation security and difficulty from a main city that have an airport to the city will have the base etc. Over 20 criteria like these are determined which are categorized in social, political, economic and military aspects. As a result all the criteria and three alternatives are evaluated by different people who have background and experience to weight the criteria and alternatives as it must be in AHP and ANP evaluation system. The alternatives got their degrees all between 0 – 1 and the total is 1. At the end the DSS advices one of the alternatives as the best one to the decision maker according to the developed model and the evaluations of the experts.

Keywords: analytic hierarchical process, analytic network process, fuzzy logic, naval base place selection, multiple criteria decision making

Procedia PDF Downloads 376
2107 The Effect of Salinity on Symbiotic Nitrogen Fixation in Alfalfa and Faba Bean

Authors: Mouffok Ahlem, Belhamra Mohamed, Mouffok Sihem

Abstract:

The use of nitrogen fertilizers inevitable consequence, the increase in the nitrate content of water, which may contribute to the production of nitrite and the formation of carcinogenic nitrosamines. The nitrogen fertilizer may also affect the structure and function of the microbial community. And the fight against eutrophication of aquatic environments represents a cost to the student statements. The agronomic, ecological and economic legumes such as faba beans and alfalfa are not demonstrated, especially in the case of semi-arid and arid areas. Osmotic stress due to drought and / or salinity deficit, nutritional deficiencies is the major factors limiting symbiotic nitrogen fixation and productivity of pulses. To study the symbiotic nitrogen fixation in faba bean (Vicia faba L.) and alfalfa (Medicago sativa L.) in the region of Biskra, we used soil samples collected from 30 locations. This work has identified several issues of ecological and agronomic interest. Evaluation of symbiotic potential of soils in the region of Biskra; by trapping technique, show different levels of susceptibility to rhizobial microflora. The effectiveness of the rhizobial symbiosis in both legumes indicates that air dry biomass and the amount of nitrogen accumulated in the aerial part, depends mainly on the rate of nodulation and regardless of the species and locality. The correlation between symbiotic nitrogen fixation and some physico-chemical properties of soils shows that symbiotic nitrogen fixation in both legumes is strongly related to soil conditions of the soil. Salinity disrupts the physiological process of growth, development and more particularly that of the symbiotic fixation of atmospheric nitrogen. Against by phosphorus promotes rhizobial symbiosis.

Keywords: rhizobia, faba bean, alfalfa, salinity

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2106 Automated Natural Hazard Zonation System with Internet-SMS Warning: Distributed GIS for Sustainable Societies Creating Schema and Interface for Mapping and Communication

Authors: Devanjan Bhattacharya, Jitka Komarkova

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The research describes the implementation of a novel and stand-alone system for dynamic hazard warning. The system uses all existing infrastructure already in place like mobile networks, a laptop/PC and the small installation software. The geospatial dataset are the maps of a region which are again frugal. Hence there is no need to invest and it reaches everyone with a mobile. A novel architecture of hazard assessment and warning introduced where major technologies in ICT interfaced to give a unique WebGIS based dynamic real time geohazard warning communication system. A never before architecture introduced for integrating WebGIS with telecommunication technology. Existing technologies interfaced in a novel architectural design to address a neglected domain in a way never done before–through dynamically updatable WebGIS based warning communication. The work publishes new architecture and novelty in addressing hazard warning techniques in sustainable way and user friendly manner. Coupling of hazard zonation and hazard warning procedures into a single system has been shown. Generalized architecture for deciphering a range of geo-hazards has been developed. Hence the developmental work presented here can be summarized as the development of internet-SMS based automated geo-hazard warning communication system; integrating a warning communication system with a hazard evaluation system; interfacing different open-source technologies towards design and development of a warning system; modularization of different technologies towards development of a warning communication system; automated data creation, transformation and dissemination over different interfaces. The architecture of the developed warning system has been functionally automated as well as generalized enough that can be used for any hazard and setup requirement has been kept to a minimum.

Keywords: geospatial, web-based GIS, geohazard, warning system

Procedia PDF Downloads 381
2105 Usability Assessment of a Bluetooth-Enabled Resistance Exercise Band among Young Adults

Authors: Lillian M. Seo, Curtis L. Petersen, Ryan J. Halter, David Kotz, John A. Batsis

Abstract:

Background: Resistance-based exercises effectively enhance muscle strength, which is especially important in older populations as it reduces the risk of disability. Our group developed a Bluetooth-enabled handle for resistance exercise bands that wirelessly transmits relative force data through low-energy Bluetooth to a local smartphone or similar device. The system has the potential to measure home-based exercise interventions, allowing health professionals to monitor compliance. Its feasibility has already been demonstrated in both clinical and field-based settings, but it remained unclear whether the system’s usability persisted upon repeated use. The current study sought to assess the usability of this system and its users’ satisfaction with repeated use by deploying the device among younger adults to gather formative information that can ultimately improve the device’s design for older adults. Methods: A usability study was conducted in which 32 participants used the above system. Participants executed 10 repetitions of four commonly performed exercises: bicep flexion, shoulder abduction, elbow extension, and triceps extension. Each completed three exercise sessions, separated by at least 24 hours to minimize muscle fatigue. At its conclusion, subjects completed an adapted version of the usefulness, satisfaction, and ease (USE) questionnaire – assessing the system across four domains: usability, satisfaction, ease of use, and ease of learning. The 20-item questionnaire examined how strongly a participant agrees with positive statements about the device on a seven-point Likert scale, with one representing ‘strongly disagree’ and seven representing ‘strongly agree.’ Participants’ data were aggregated to calculate mean response values for each question and domain, effectively assessing the device’s performance across different facets of the user experience. Summary force data were visualized using a custom web application. Finally, an optional prompt at the end of the questionnaire allowed for written comments and feedback from participants to elicit qualitative indicators of usability. Results: Of the n=32 participants, 13 (41%) were female; their mean age was 32.4 ± 11.8 years, and no participants had a physical impairment. No usability questions received a mean score < 5 of seven. The four domains’ mean scores were: usefulness 5.66 ± 0.35; satisfaction 6.23 ± 0.06; ease of use 6.25 ± 0.43; and ease of learning 6.50 ± 0.19. Representative quotes of the open-ended feedback include: ‘A non-rigid strap-style handle might be useful for some exercises,’ and, ‘Would need different bands for each exercise as they use different muscle groups with different strength levels.’ General impressions were favorable, supporting the expectation that the device would be a useful tool in exercise interventions. Conclusions: A simple usability assessment of a Bluetooth-enabled resistance exercise band supports a consistent and positive user experience among young adults. This study provides adequate formative data, assuring the next steps can be taken to continue testing and development for the target population of older adults.

Keywords: Bluetooth, exercise, mobile health, mHealth, usability

Procedia PDF Downloads 100
2104 Predictive Analytics in Oil and Gas Industry

Authors: Suchitra Chnadrashekhar

Abstract:

Earlier looked as a support function in an organization information technology has now become a critical utility to manage their daily operations. Organizations are processing huge amount of data which was unimaginable few decades before. This has opened the opportunity for IT sector to help industries across domains to handle the data in the most intelligent manner. Presence of IT has been a leverage for the Oil & Gas industry to store, manage and process the data in most efficient way possible thus deriving the economic value in their day-to-day operations. Proper synchronization between Operational data system and Information Technology system is the need of the hour. Predictive analytics supports oil and gas companies by addressing the challenge of critical equipment performance, life cycle, integrity, security, and increase their utilization. Predictive analytics go beyond early warning by providing insights into the roots of problems. To reach their full potential, oil and gas companies need to take a holistic or systems approach towards asset optimization and thus have the functional information at all levels of the organization in order to make the right decisions. This paper discusses how the use of predictive analysis in oil and gas industry is redefining the dynamics of this sector. Also, the paper will be supported by real time data and evaluation of the data for a given oil production asset on an application tool, SAS. The reason for using SAS as an application for our analysis is that SAS provides an analytics-based framework to improve uptimes, performance and availability of crucial assets while reducing the amount of unscheduled maintenance, thus minimizing maintenance-related costs and operation disruptions. With state-of-the-art analytics and reporting, we can predict maintenance problems before they happen and determine root causes in order to update processes for future prevention.

Keywords: hydrocarbon, information technology, SAS, predictive analytics

Procedia PDF Downloads 331
2103 Awareness of Organic Products in Bangladesh: A Marketing Perspective

Authors: Sheikh Mohammed Rafiul Huque

Abstract:

Bangladesh since its inception has been an economy that is fuelled by agriculture and agriculture has significant contribution to the GDP of Bangladesh. The agriculture of Bangladesh predominantly and historically dependent on organic sources of raw material though the place has taken in decades by inorganic sources of raw materials due to the high demand of food for rapidly growing of population. Meanwhile, a new market segment, which is niche market, has been evolving in the urban area in favor of organic products, though 71.1% population living in rural areas is dependent mainly on conventional products. The new market segment is search of healthy and safer source of food and they could believe that organic products are the solution of that. In Bangladesh, food adulteration is very common practices among the shop-keepers to extend the shelf life of raw vegetables and fruits. The niche group of city dwellers is aware about the fact and gradually shifting their buying behavior to organic products. A recent survey on organic farming revealed that 16,200 hectares under organic farming in recent time, which was only 2,500 hectares in 2008. This study is focused on consumer awareness of organic products and tried to explore the factors affecting organic food consumption among high income group of people. The hypothesis is developed to explore the effect of gender (GENDER), ability to purchase (ABILITY) and health awareness (HEALTH) on purchase intention (INTENTION). A snowball sampling was administered among the high income group of people in Dhaka city among 150 respondents. In this sampling process the study could identify only those samples who has consume organic products. A Partial Least Square (PLS) method was used to analyze data using path analysis. It was revealed from the analysis that coefficient determination R2 is 0.829 for INTENTION endogenous latent variable. This means that three latent variables (GENDER, ABILITY, and HEALTH) significantly explain 82.9% of the variance in INTENTION of purchasing organic products. Moreover, GENDER solely explains 6.3% and 8.6% variability of ABILITY and HEALTH respectively. The inner model suggests that HEALTH has strongest negative effect on INTENTION (-0.647) followed by ABILITY (0.344) and GENDER (0.246). The hypothesized path relationship between ABILITY->INTENTION, HEALTH->INTENTION and GENDER->INTENTION are statistically significant. Furthermore, the hypothesized path relationship between GENDER->ABILITY (0.262) and GENDER->HEALTH (-0.292) also statistically significant. The purpose of the study is to demonstrate how an organic product producer can improve his participatory guarantee system (PGS) while marketing the products. The study focuses on understanding gender (GENDER), ability (ABILITY) and health (HEALTH) factors while positioning the products (INTENTION) in the mind of the consumer. In this study, the respondents are found to care about high price and ability to purchase variables with loading -0.920 and 0.898. They are good indicators of ability to purchase (ABILITY). The marketers should consider about price of organic comparing to conventional products while marketing, otherwise, that will create negative intention to buy with a loading of -0.939. Meanwhile, it is also revealed that believability of chemical free component in organic products and health awareness affects health (HEALTH) components with high loading -0.941 and 0.682. The study analyzes that low believability of chemical free component and high price of organic products affects intension to buy. The marketers should not overlook this point while targeting the consumers in Bangladesh.

Keywords: health awareness, organic products, purchase ability, purchase intention

Procedia PDF Downloads 359
2102 Early Evaluation of Long-Span Suspension Bridges Using Smartphone Accelerometers

Authors: Ekin Ozer, Maria Q. Feng, Rupa Purasinghe

Abstract:

Structural deterioration of bridge systems possesses an ongoing threat to the transportation networks. Besides, landmark bridges’ integrity and safety are more than sole functionality, since they provide a strong presence for the society and nations. Therefore, an innovative and sustainable method to inspect landmark bridges is essential to ensure their resiliency in the long run. In this paper, a recently introduced concept, smartphone-based modal frequency estimation is addressed, and this paper targets to authenticate the fidelity of smartphone-based vibration measurements gathered from three landmark suspension bridges. Firstly, smartphones located at the bridge mid-span are adopted as portable and standalone vibration measurement devices. Then, their embedded accelerometers are utilized to gather vibration response under operational loads, and eventually frequency domain characteristics are deduced. The preliminary analysis results are compared with the reference publications and high-quality monitoring data to validate the usability of smartphones on long-span landmark suspension bridges. If the technical challenges such as high period of vibration, low amplitude excitation, embedded smartphone sensor features, sampling, and citizen engagement are tackled, smartphones can provide a novel and cost-free crowdsourcing tool for maintenance of these landmark structures. This study presents the early phase findings from three signature structures located in the United States.

Keywords: smart and mobile sensing, structural health monitoring, suspension bridges, vibration analysis

Procedia PDF Downloads 270
2101 The Impact of Ozone on the Sensory Perception of Pumpkin Seeds and its Toxicity against Plodia interpunctella (Lepidoptera: Pyralidae)

Authors: Saba Goudarzi Dehrizifar, Aysan Afradi

Abstract:

The utilization of ozone treatment as a potential technique for storage pest control has gained significant attention. This approach presents an alternative to traditional chemical methods. In the current study, the mortality rates of Plodia interpunctella as a primary pest found in stored products particularly nuts, were examined after being exposed to different O3 concentration (minimum, half, and maximum) in three replicates and within 24 hours. As the concentration of O3 increased, the mortality rates of P. interpunctella also experienced a dramatic growth. A 20-member panel (men and women in different ages), formed from the society community, was selected for sensory evaluation. The pumpkin seeds samples were coded and presented randomly in identical containers. The panelists were asked to evaluate their degree of liking or disliking on a seven-point hedonic scale using descriptive categories, ranging 1-7 (1: extremely dislike, 2: very dislike, 3: dislike, 4: no difference, 5: like, 6: very like, and 7: extremely like). The results obtained from experiments on the qualitative characteristics of the studied dates through the sensory test revealed that O3 concentration did not affect their color, crispness, firmness, and overall acceptance and the half concentration of ozone on pumpkin seed had the highest consumption interest. Moreover, minimal alterations were observed in the aroma of the pumpkin seeds, which could be resolved with a short period of air exposure. Therefore, it could be concluded that the atmospheric O3 gas provided a cost-effective and environmentally friendly way for controlling the insect pests in pumpkin seeds, besides preserving their sensory and quality properties.

Keywords: zone, control, pumpkin seeds, qualitative characteristics

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2100 The Influence of Guided and Independent Training Toward Teachers’ Competence to Plan Early Childhood Education Learning Program

Authors: Sofia Hartati

Abstract:

This research is aimed at describing training in early childhood education program empirically, describing teachers ability to plan lessons empirically, and acquiring empirical data as well as analyzing the influence of guided and independent training toward teachers competence in planning early childhood learning program. The method used is an experiment. It collected data with a population of 76 early childhood educators in Tunjung Teja Sub District area through random sampling technique and grouped into two namely 38 people in an experiment class and 38 people in a controlled class. The technique used for data collections is a test. The result of the research shows that there is a significant influence between training for guided educators toward Teachers Ability toward Planning Early Childhood Learning Program. Guided training has been proven to improve the ability to comprehend planning a learning program. The ability to comprehend planning a learning program owned by teachers of early childhood program comprises of 1) determining the characteristics and competence of students prior to learning; 2) formulating the objective of the learning; 3) selecting materials and its sequences; 4) selecting teaching methods; 5) determining the means or learning media; 6) selecting evaluation strategy as a part of teachers pedagogic competence. The result of this research describes a difference in the competence level of teachers who have joined guided training which is relatively higher than the teachers who joined the independent training. Guided training is one of an effective way to improve the knowledge and competence of early childhood educators.

Keywords: competence, planning, teachers, training

Procedia PDF Downloads 245
2099 A Numerical Study on Semi-Active Control of a Bridge Deck under Seismic Excitation

Authors: A. Yanik, U. Aldemir

Abstract:

This study investigates the benefits of implementing the semi-active devices in relation to passive viscous damping in the context of seismically isolated bridge structures. Since the intrinsically nonlinear nature of semi-active devices prevents the direct evaluation of Laplace transforms, frequency response functions are compiled from the computed time history response to sinusoidal and pulse-like seismic excitation. A simple semi-active control policy is used in regard to passive linear viscous damping and an optimal non-causal semi-active control strategy. The control strategy requires optimization. Euler-Lagrange equations are solved numerically during this procedure. The optimal closed-loop performance is evaluated for an idealized controllable dash-pot. A simplified single-degree-of-freedom model of an isolated bridge is used as numerical example. Two bridge cases are investigated. These cases are; bridge deck without the isolation bearing and bridge deck with the isolation bearing. To compare the performances of the passive and semi-active control cases, frequency dependent acceleration, velocity and displacement response transmissibility ratios Ta(w), Tv(w), and Td(w) are defined. To fully investigate the behavior of the structure subjected to the sinusoidal and pulse type excitations, different damping levels are considered. Numerical results showed that, under the effect of external excitation, bridge deck with semi-active control showed better structural performance than the passive bridge deck case.

Keywords: bridge structures, passive control, seismic, semi-active control, viscous damping

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2098 Collagen Scaffold Incorporated with Macrotyloma uniflorum Plant Extracts as a–Burn/Wound Dressing Material, in Vitro and in Vivo Evaluation

Authors: Thangavelu Muthukumar, Thotapalli Parvathaleswara Sastry

Abstract:

Collagen is the most abundantly available connective tissue protein, which is being used as a biomaterial for various biomedical applications. Presently, fish wastes are disposed improperly which is causing serious environmental pollution resulting in offensive odour. Fish scales are promising source of Type I collagen. Medicinal plants have been used since time immemorial for treatment of various ailments of skin and dermatological disorders especially cuts, wounds, and burns. Developing biomaterials from the natural sources which are having wound healing properties within the search of a common man is the need of hour, particularly in developing and third world countries. With these objectives in view we have developed a wound dressing material containing fish scale collagen (FSC) incorporated with Macrotyloma uniflorum plant extract (PE). The wound dressing composite was characterized for its physiochemical properties using conventional methods. SEM image revealed that the composite has fibrous and porous surface which helps in transportation of oxygen as well as absorbing wound fluids. The biomaterial has shown 95% biocompatibility with required mechanical strength and has exhibited antimicrobial properties. This biomaterial has been used as a wound dressing material in experimental wounds of rats. The healing pattern was evaluated by macroscopic observations, panimetric studies, biochemical, histopathological observations. The results showed faster healing pattern in the wounds treated with CSPE compared to the other composites used in this study and untreated control. These experiments clearly suggest that CSPE can be used as wound/burn dressing materials.

Keywords: collagen, wound dressing, Macrotyloma uniflorum, burn dressing

Procedia PDF Downloads 391
2097 Evaluation of Newly Synthesized Steroid Derivatives Using In silico Molecular Descriptors and Chemometric Techniques

Authors: Milica Ž. Karadžić, Lidija R. Jevrić, Sanja Podunavac-Kuzmanović, Strahinja Z. Kovačević, Anamarija I. Mandić, Katarina Penov-Gaši, Andrea R. Nikolić, Aleksandar M. Oklješa

Abstract:

This study considered selection of the in silico molecular descriptors and the models for newly synthesized steroid derivatives description and their characterization using chemometric techniques. Multiple linear regression (MLR) models were established and gave the best molecular descriptors for quantitative structure-retention relationship (QSRR) modeling of the retention of the investigated molecules. MLR models were without multicollinearity among the selected molecular descriptors according to the variance inflation factor (VIF) values. Used molecular descriptors were ranked using generalized pair correlation method (GPCM). In this method, the significant difference between independent variables can be noticed regardless almost equal correlation between dependent variable. Generated MLR models were statistically and cross-validated and the best models were kept. Models were ranked using sum of ranking differences (SRD) method. According to this method, the most consistent QSRR model can be found and similarity or dissimilarity between the models could be noticed. In this study, SRD was performed using average values of experimentally observed data as a golden standard. Chemometric analysis was conducted in order to characterize newly synthesized steroid derivatives for further investigation regarding their potential biological activity and further synthesis. This article is based upon work from COST Action (CM1105), supported by COST (European Cooperation in Science and Technology).

Keywords: generalized pair correlation method, molecular descriptors, regression analysis, steroids, sum of ranking differences

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2096 Business Intelligence Dashboard Solutions for Improving Decision Making Process: A Focus on Prostate Cancer

Authors: Mona Isazad Mashinchi, Davood Roshan Sangachin, Francis J. Sullivan, Dietrich Rebholz-Schuhmann

Abstract:

Background: Decision-making processes are nowadays driven by data, data analytics and Business Intelligence (BI). BI as a software platform can provide a wide variety of capabilities such as organization memory, information integration, insight creation and presentation capabilities. Visualizing data through dashboards is one of the BI solutions (for a variety of areas) which helps managers in the decision making processes to expose the most informative information at a glance. In the healthcare domain to date, dashboard presentations are more frequently used to track performance related metrics and less frequently used to monitor those quality parameters which relate directly to patient outcomes. Providing effective and timely care for patients and improving the health outcome are highly dependent on presenting and visualizing data and information. Objective: In this research, the focus is on the presentation capabilities of BI to design a dashboard for prostate cancer (PC) data that allows better decision making for the patients, the hospital and the healthcare system related to a cancer dataset. The aim of this research is to customize a retrospective PC dataset in a dashboard interface to give a better understanding of data in the categories (risk factors, treatment approaches, disease control and side effects) which matter most to patients as well as other stakeholders. By presenting the outcome in the dashboard we address one of the major targets of a value-based health care (VBHC) delivery model which is measuring the value and presenting the outcome to different actors in HC industry (such as patients and doctors) for a better decision making. Method: For visualizing the stored data to users, three interactive dashboards based on the PC dataset have been developed (using the Tableau Software) to provide better views to the risk factors, treatment approaches, and side effects. Results: Many benefits derived from interactive graphs and tables in dashboards which helped to easily visualize and see the patients at risk, better understanding the relationship between patient's status after treatment and their initial status before treatment, or to choose better decision about treatments with fewer side effects regarding patient status and etc. Conclusions: Building a well-designed and informative dashboard is related to three important factors including; the users, goals and the data types. Dashboard's hierarchies, drilling, and graphical features can guide doctors to better navigate through information. The features of the interactive PC dashboard not only let doctors ask specific questions and filter the results based on the key performance indicators (KPI) such as: Gleason Grade, Patient's Age and Status, but may also help patients to better understand different treatment outcomes, such as side effects during the time, and have an active role in their treatment decisions. Currently, we are extending the results to the real-time interactive dashboard that users (either patients and doctors) can easily explore the data by choosing preferred attribute and data to make better near real-time decisions.

Keywords: business intelligence, dashboard, decision making, healthcare, prostate cancer, value-based healthcare

Procedia PDF Downloads 127
2095 Comparative Evaluation of Vanishing Interfacial Tension Approach for Minimum Miscibility Pressure Determination

Authors: Waqar Ahmad Butt, Gholamreza Vakili Nezhaad, Ali Soud Al Bemani, Yahya Al Wahaibi

Abstract:

Minimum miscibility pressure (MMP) plays a great role in determining the displacement efficiency of different gas injection processes. Experimental techniques for MMP determination include industrially recommended slim tube, vanishing interfacial tension (VIT) and rising bubble apparatus (RBA). In this paper, MMP measurement study using slim tube and VIT experimental techniques for two different crude oil samples (M and N) both in live and stock tank oil forms is being presented. VIT measured MMP values for both 'M' and 'N' live crude oils were close to slim tube determined MMP values with 6.4 and 5 % deviation respectively. Whereas for both oil samples in stock tank oil form, VIT measured MMP showed a higher unacceptable deviation from slim tube determined MMP. This higher difference appears to be related to high stabilized crude oil heavier fraction and lack of multiple contacts miscibility. None of the different nine deployed crude oil and CO2 MMP computing correlations could result in reliable MMP, close to slim tube determined MMP. Since VIT determined MMP values for both considered live crude oils are in close match with slim tube determined MMP values, it confirms reliable, reproducible, rapid and cheap alternative for live crude oil MMP determination. Whereas VIT MMP determination for stock tank oil case needed further investigation about stabilization / destabilization mechanism of oil heavier ends and multiple contacts miscibility development issues.

Keywords: minimum miscibility pressure, interfacial tension, multiple contacts miscibility, heavier ends

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2094 Evaluation of Virtual Reality for the Rehabilitation of Athlete Lower Limb Musculoskeletal Injury: A Method for Obtaining Practitioner’s Viewpoints through Observation and Interview

Authors: Hannah K. M. Tang, Muhammad Ateeq, Mark J. Lake, Badr Abdullah, Frederic A. Bezombes

Abstract:

Based on a theoretical assessment of current literature, virtual reality (VR) could help to treat sporting injuries in a number of ways. However, it is important to obtain rehabilitation specialists’ perspectives in order to design, develop and validate suitable content for a VR application focused on treatment. Subsequently, a one-day observation and interview study focused on the use of VR for the treatment of lower limb musculoskeletal conditions in athletes was conducted at St George’s Park England National Football Centre with rehabilitation specialists. The current paper established the methods suitable for obtaining practitioner’s viewpoints through observation and interview in this context. Particular detail was provided regarding the method of qualitatively processing interview results using the qualitative data analysis software tool NVivo, in order to produce a narrative of overarching themes. The observations and overarching themes identified could be used as a framework and success criteria of a VR application developed in future research. In conclusion, this work explained the methods deemed suitable for obtaining practitioner’s viewpoints through observation and interview. This was required in order to highlight characteristics and features of a VR application designed to treat lower limb musculoskeletal injury of athletes and could be built upon to direct future work.

Keywords: athletes, lower-limb musculoskeletal injury, rehabilitation, return-to-sport, virtual reality

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2093 Formulation and in vitro Evaluation of Transdermal Delivery of Articaine

Authors: Dinakaran Venkatachalam, Paul Chambers, Kavitha Kongara, Preet Singh

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The objective of this study is to formulate different topical preparations containing articaine and to investigate their permeation through goat skin. Initially, articaine and its hydrochloride salt were compared for in vitro permeation using Franz cell model. Goat skin samples were collected after euthanizing male goat kids purchased from the dairy goat farmers. Subcutaneous fat was removed and the skin was mounted on the donor chamber (orifice area 1.00 cm²) and drugs were applied onto the epidermis. Phosphate buffer saline (pH 7.4) was used to maintain sink condition in the receptor chamber (8 ml) of the Franz cell. Samples (0.4 ml) were collected at various intervals over 24 hours after each sampling equal volume of PBS was replaced in the receptor chamber. Articaine in the collected samples were quantified using LC/MS. The results suggested that articaine free base permeates better than its hydrochloride salt through goat skin. This study results support the fact that local anesthetics in its base form are lipophilic and thus penetrates faster through cell membranes than their salts. Later, articaine free base was formulated either using ethanol and octyl salicylate or dimethyl sulfoxide (DMSO) as penetration enhancers and was compared for in vitro permeation. The transdermal flux of articaine in the formulation containing DMSO was approximately 3.8 times higher than that of the formulation containing ethanol and octyl salicylate. Further studies to evaluate the local anesthetic efficacy of the topical formulation containing articaine for dermal anesthesia in animals have been planned.

Keywords: articaine, dermal anesthesia, local anesthetic, transdermal

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2092 Outcome Analysis of Surgical and Nonsurgical Treatment on Indicated Operative Chronic Subdural Hematoma: Serial Case in Cipto Mangunkusumo Hospital Indonesia

Authors: Novie Nuraini, Sari Hanifa, Yetty Ramli

Abstract:

Chronic subdural hematoma (cSDH) is a common condition after head trauma. Although the size of the thickness of cSDH has an important role in the decision to perform surgery, but the size limit of the thickness is not absolute. In this serial case report, we evaluate three case report of cSDH that indicated to get the surgical procedure because of deficit neurologic and neuroimaging finding with subfalcine herniation more than 0.5 cm and hematoma thickness more than one cm. On the first case, the patient got evacuation hematoma procedure, but the second and third case, we did nonsurgical treatment because the patient and family refused to do the operation. We did the conservative treatment with bed rest and mannitol. Serial radiologic evaluation is done when we found worsening condition. We also reevaluated radiologic examination two weeks after the treatment. The results in this serial case report, the first and second case have a good outcome. On the third case, there was a worsening condition, which in this patient there was a comorbid with type two diabetic mellitus, pneumonie and chronic kidney disease. Some conservative treatment such as bed rest, corticosteroid, mannitol or the other hyperosmolar has a good outcome in patient without neurologic deficits, small hematoma, and or patient without comorbid disease. Evacuate hematome is the best choice in cSDH treatment with deficit neurologic finding. Afterall, there is some condition that we can not do the surgical procedure. Serial radiologic examination needed after two weeks to evaluate the treatment or if there is any worsening condition.

Keywords: chronic subdural hematoma, traumatic brain injury, surgical treatment, nonsurgical treatment, outcome

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2091 Evaluation of the Biological Activities of Chrysin as an Important Perspective in the Treatment of Infectious and Cancer Diseases

Authors: Sajjad Jafari, Reza Akbari

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Background and Aim: Chrysin, a flavonoid compound found in medicinal plants, honey, and propolis, has potential biological activities that make it an important perspective in the treatment of infectious and cancer diseases. The aim of this review study is to evaluate the biological activities of chrysin in the treatment of infectious and cancer diseases. Material and Methods: The present study is a review study that searched reputable scientific databases such as PubMed, Google Scholar, Scopus, and Web of Science from 2000 to 2023 using keywords such as antimicrobial, antifungal, chrysin, anticancer, antioxidants, and infectious diseases. The researchers examined 25 articles to determine the biological activities of chrysin. Results: Chrysin has high inhibitory or lethal activities on gram-positive and gram-negative bacteria, including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Enterococcus faeces. It also has anti-biofilm effects and antifungal effects on strains such as Aspergillus niger and Candida albicans. Chrysin also has anticancer effects on various cancers, including colorectal cancer, pancreatic cancer, breast cancer, and MCF-7 cancer, which have been confirmed in vitro and in vivo. Conclusion: Chrysin has the potential as an important therapeutic option in the treatment of infectious and cancer diseases. Its high antimicrobial and anticancer activities, combined with its low toxicity in nanoparticle form, make it a promising candidate for further clinical trials. The production of anti-microbial and anti-cancer drugs from natural substances, such as chrysin, is a valuable contribution to the field of medicine.

Keywords: chrysin, antimicrobial, anticancer, infectious diseases

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2090 Performance Evaluation of Filtration System for Groundwater Recharging Well in the Presence of Medium Sand-Mixed Storm Water

Authors: Krishna Kumar Singh, Praveen Jain

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The collection of storm water runoff and forcing it into the groundwater is the need of the hour to sustain the ground water table. However, the runoff entraps various types of sediments and other floating objects whose removal are essential to avoid pollution of ground water and blocking of pores of aquifer. However, it requires regular cleaning and maintenance due to the problem of clogging. To evaluate the performance of filter system consisting of coarse sand (CS), gravel (G) and pebble (P) layers, a laboratory experiment was conducted in a rectangular column. The effect of variable thickness of CS, G and P layers of the filtration unit of the recharge shaft on the recharge rate and the sediment concentration of effluent water were evaluated. Medium sand (MS) of three particle sizes, viz. 0.150–0.300 mm (T1), 0.300–0.425 mm (T2) and 0.425–0.600 mm of thickness 25 cm, 30 cm, and 35 cm respectively in the top layer of the filter system and having seven influent sediment concentrations of 250–3,000 mg/l were used for the experimental study. The performance was evaluated in terms of recharge rates and clogging time. The results indicated that 100 % suspended solids were entrapped in the upper 10 cm layer of MS, the recharge rates declined sharply for influent concentrations of more than 1,000 mg/l. All treatments with a higher thickness of MS media indicated recharge rate slightly more than that of all treatment with a lower thickness of MS media respectively. The performance of storm water infiltration systems was highly dependent on the formation of a clogging layer at the filter. An empirical relationship has been derived between recharge rates, inflow sediment load, size of MS and thickness of MS with using MLR.

Keywords: groundwater, medium sand-mixed storm water filter, inflow sediment load

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2089 Evaluation of Produced Water Treatment Using Advanced Oxidation Processes and Sodium Ferrate(VI)

Authors: Erica T. R. Mendonça, Caroline M. B. de Araujo, Filho, Osvaldo Chiavone, Sobrinho, Maurício A. da Motta

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Oil and gas exploration is an essential activity for modern society, although the supply of its global demand has caused enough damage to the environment, mainly due to produced water generation, which is an effluent associated with the oil and gas produced during oil extraction. It is the aim of this study to evaluate the treatment of produced water, in order to reduce its oils and greases content (OG), by using flotation as a pre-treatment, combined with oxidation for the remaining organic load degradation. Thus, there has been tested Advanced Oxidation Process (AOP) using both Fenton and photo-Fenton reactions, as well as a chemical oxidation treatment using sodium ferrate(VI), Na2[FeO4], as a strong oxidant. All the studies were carried out using real samples of produced water from petroleum industry. The oxidation process using ferrate(VI) ion was studied based on factorial experimental designs. The factorial design was used in order to study how the variables pH, temperature and concentration of Na2[FeO4] influences the O&G levels. For the treatment using ferrate(VI) ion, the results showed that the best operating point is obtained when the temperature is 28 °C, pH 3, and a 2000 mg.L-1 solution of Na2[FeO4] is used. This experiment has achieved a final O&G level of 4.7 mg.L-1, which means 94% percentage removal efficiency of oils and greases. Comparing Fenton and photo-Fenton processes, it was observed that the Fenton reaction did not provide good reduction of O&G (around 20% only). On the other hand, a degradation of approximately 80.5% of oil and grease was obtained after a period of seven hours of treatment using photo-Fenton process, which indicates that the best process combination has occurred between the flotation and the photo-Fenton reaction using solar radiation, with an overall removal efficiency of O&G of approximately 89%.

Keywords: advanced oxidation process, ferrate (VI) ion, oils and greases removal, produced water treatment

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2088 Rethink Urban Resilience: An Introductory Study Towards Resilient Spatial Structure of Refugees Neighborhoods

Authors: Salwa Mohammad Alawneh

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The ongoing humanitarian crises spur rapid and unpredicted refugee influxes resulting in demographic changes in cities. Regarding different urban systems are vulnerable in refugee neighborhoods. With the consequent social, economic, and spatial challenges, cities must respond with a more durable and sustainable approach based on urban resilience. The paper systematically approaches urban resilience to contribute to refugee spaces by reflecting on the overall urban systems of their neighborhoods. The research will review the urban resilience literature to develop an evaluation framework. The developed framework applies urban resilience more holistically in refugee neighborhoods and expands to the urban systems of social, economic, and spatial. However, the main highlight of this paper is the resilient spatial structure in refugee neighborhoods to face the internal and complex stress of refugee waves and their demographic changes. Finding a set of resilient spatial measurements and focusing on urban forms at a neighborhood scale provide vulnerability reduction and enhance adaptation capacity. As a model example, the paper applies these measurements and facilitates geospatial technologies to one of the refugee neighborhoods in Amman, Jordan, namely Al-Jubilee. The application in Al-Jubilee helps to demonstrate a road map towards a developmental pattern in design and planning by different decision-makers of inter-governmental and humanitarian organizations. In this regard, urban resilience improves the humanitarian assistantship of refugee settings beyond providing the essential needs. In conclusion, urban resilience responds to the different challenges of refugee neighborhoods by supporting urban stability, improving livability, and maintaining both urban functions and security.

Keywords: urban resilience of refugee, resilient urban form, refugee neighborhoods, humanitarian assistantship, refugee in Jordan

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2087 Implementing Service Learning in the Health Education Curriculum

Authors: Karen Butler

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Johnson C. Smith University, one of the nation’s oldest Historically Black Colleges and Universities, has a strong history of service learning and community service. We first integrated service learning and peer education into health education courses in the spring of 2000. Students enrolled in the classes served as peer educators for the semester. Since then, the program has evolved and expanded but remains an integral part of several courses. The purpose of this session is to describe our program in terms of development, successes, and obstacles, and feedback received. A detailed description of the service learning component in HED 235: Drugs and Drug Education and HED 337: Environmental Health will be provided. These classes are required of our Community Health majors but are also popular electives for students in other disciplines. Three sources of student feedback were used to evaluate and continually modify the component: the SIR II course evaluation, service learning reflection papers, and focus group interviews. Student feedback has been largely positive. When criticism was given, it was thoughtful and constructive – given in the spirit of making it better for the next group. Students consistently agreed that the service learning program increased their awareness of pertinent health issues; that both the service providers and service recipients benefited from the project; and that the goals/issues targeted by the service learning component fit the objectives of the course. Also, evidence of curriculum and learning enhancement was found in the reflection papers and focus group sessions. Service learning sets up a win-win situation. It provides a way to respond to campus and community health needs while enhancing the curriculum, as students learn more by doing things that benefit the health and wellness of others. Service learning is suitable for any health education course and any target audience would welcome the effort.

Keywords: black colleges, community health, health education, service learning

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2086 Estimation of Constant Coefficients of Bourgoyne and Young Drilling Rate Model for Drill Bit Wear Prediction

Authors: Ahmed Z. Mazen, Nejat Rahmanian, Iqbal Mujtaba, Ali Hassanpour

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In oil and gas well drilling, the drill bit is an important part of the Bottom Hole Assembly (BHA), which is installed and designed to drill and produce a hole by several mechanisms. The efficiency of the bit depends on many drilling parameters such as weight on bit, rotary speed, and mud properties. When the bit is pulled out of the hole, the evaluation of the bit damage must be recorded very carefully to guide engineers in order to select the bits for further planned wells. Having a worn bit for hole drilling may cause severe damage to bit leading to cutter or cone losses in the bottom of hole, where a fishing job will have to take place, and all of these will increase the operating cost. The main factor to reduce the cost of drilling operation is to maximize the rate of penetration by analyzing real-time data to predict the drill bit wear while drilling. There are numerous models in the literature for prediction of the rate of penetration based on drilling parameters, mostly based on empirical approaches. One of the most commonly used approaches is Bourgoyne and Young model, where the rate of penetration can be estimated by the drilling parameters as well as a wear index using an empirical correlation, provided all the constants and coefficients are accurately determined. This paper introduces a new methodology to estimate the eight coefficients for Bourgoyne and Young model using the gPROMS parameters estimation GPE (Version 4.2.0). Real data collected form similar formations (12 ¼’ sections) in two different fields in Libya are used to estimate the coefficients. The estimated coefficients are then used in the equations and applied to nearby wells in the same field to predict the bit wear.

Keywords: Bourgoyne and Young model, bit wear, gPROMS, rate of penetration

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2085 Pattern of Biopsy Proven Renal Disease and Association between the Clinical Findings with Renal Pathology in Eastern Nepal

Authors: Manish Subedi, Bijay Bartaula, Ashok R. Pant, Purbesh Adhikari, Sanjib K. Sharma

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Background: The pattern of glomerular disease varies worldwide. In absence of kidney disease/Kidney biopsy registry in Nepal, the exact etiology of different forms of glomerular disease is primarily unknown in our country. Method: We retrospectively analyzed 175 cases of renal biopsies performed from dated September 2014 to August 2016 at B. P. Koirala Institute of Health Sciences, Dharan, Nepal. Results: The commonest indication for renal biopsy was nephrotic syndrome (34.9%), followed by Systemic lupus erythematosus with suspected renal involvement (22.3%). Majority of patients were in the 30-60 year bracket (57.2%), with the mean age of the patients being 35.37 years. The average number of glomeruli per core was 13, with inadequate sampling in 5.1%. IgA nephropathy (17%) was found to be the most common primary glomerular disease, followed by membranous nephropathy (14.6%) and FSGS (14.6%). The commonest secondary glomerular disease was lupus nephritis. Complications associated with renal biopsy were pain at biopsy site in 18% of cases, hematuria in 6% and perinephric hematoma in 4% cases. Conclusion: The commonest primary and secondary glomerular disease was IgA nephropathy and lupus nephritis respectively. The high prevalence of Systemic lupus erythematosus with lupus nephritis among Nepalese in comparison with other developing countries warrants further evaluation. As an initial attempt towards documentation of glomerular diseases in the national context, this study should serve as a stepping stone towards the eventual establishment of a full-fledged national registry of glomerular diseases in Nepal.

Keywords: glomerular, Nepal, renal biopsy, systemic lupus erythematoses

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2084 Immunohistochemical Evaluation of Moringa oleifera Seed Oil in Cadmium Induced Frontal Cortex Damage in Wistar Rats

Authors: Olusegun D. Omotoso

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The use of Moringa oleifera seed oil in the prevention and cure of many ailments particularly, neurodegenerative diseases have been on increasing trend in Nigeria. The study was aimed at investigating the ameliorative or reversal effects by the intervention of Moringa oleifera seed oil on the damage to frontal cortex of Wistar rats by cadmium. Twenty-eight Wistar rats of both sexes weighed between 73g-151g were used. The animals were acclimatized and were fed on rat chow and water ad libitum. The rats were randomly divided into four groups A, B, C and D of 7 rats each. Group A served as control which received 2.5mg/kgbw phosphate buffer intra-peritoneally, while group D served as Moringa-treated control and received oral administration of 2.0 mg/kgbw Moringa oleifera oil. Groups B and C were injected intra-peritoneally with 3.5mg/kgbw CdSO₄.8H₂O single dose. Group C received orally administration of 2.0mg/kgbw Moringa oleifera oil. The intervention lasted for four weeks after which the animals were sacrificed by cervical dislocation and the tissues processed histologically. The immuno-histoarchitecture of the frontal cortex was characterized by pyknosis of nuclei as well as activation of astrocytes which was evidence in group B rats, while those animals in group C showed ameliorative effect that were evidence in reduction in the number of pyknotic nuclei and reduction of activated astrocytes as compared with control group A and Moringa-treated group D. It can be deduced that Moringa oleifera seed oil has natural antioxidant constituents that might have ameliorated the immuno-histoarchitectural damage caused by cadmium.

Keywords: cadmium, immuno-histoarchitecture, Moringa oleifera, pyknotic nuclei

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2083 Moving from Practice to Theory

Authors: Maria Lina Garrido

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This paper aims to reflect upon instruction in English classes with the specific purpose of reading comprehension development, having as its paradigm the considerations presented by William Grabe, in his book Reading in a Second Language: Moving from theory to practice. His concerns regarding the connection between research findings and instructional practices have stimulated the present author to re-evaluate both her long practice as an English reading teacher and as the author of two reading textbooks for graduate students. Elements of the reading process such as linguistic issues, prior knowledge, reading strategies, critical evaluation, and motivation are the main foci of this analysis as far as the activities developed in the classroom are concerned. The experience with university candidates on postgraduate courses with different levels of English knowledge in Bahia, Brazil, has definitely demanded certain adjustments to this author`s classroom setting. Word recognition based on cognates, for example, has been emphasized given the fact that academic texts use many Latin words which have the same roots as the Brazilian Portuguese lexicon. Concerning syntactic parsing, the tenses/verbal aspects, modality and linking words are included in the curriculum, but not with the same depth as the general English curricula. Reading strategies, another essential predictor for developing reading skills, have been largely stimulated in L2 classes in order to compensate for a lack of the appropriate knowledge of the foreign language. This paper presents results that demonstrate that this author`s teaching practice is compatible with the implications and instruction concerning the reading process outlined by Grabe, however, it admits that each class demands specific instructions to meet the needs of that particular group.

Keywords: classroom practice, instructional activities, reading comprehension, reading skills

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2082 Evaluation of Pile Performance in Different Layers of Soil

Authors: Orod Zarrin, Mohesn Ramezan Shirazi, Hassan Moniri

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The use of pile foundations technique is developed to support structures and buildings on soft soil. The most important dynamic load that can affect the pile structure is earthquake vibrations. Pile foundations during earthquake excitation indicate that piles are subject to damage by affecting the superstructure integrity and serviceability. During an earthquake, two types of stresses can damage the pile head, inertial load that is caused by superstructure and deformation which caused by the surrounding soil. Soil deformation and inertial load are associated with the acceleration developed in an earthquake. The acceleration amplitude at the ground surface depends on the magnitude of earthquakes, soil properties and seismic source distance. According to the investigation, the damage is between the liquefiable and non-liquefiable layers and also soft and stiff layers. This damage crushes the pile head by increasing the inertial load which is applied by the superstructure. On the other hand, the cracks on the piles due to the surrounding soil are directly related to the soil profile and causes cracks from small to large. However, the large cracks reason have been listed such as liquefaction, lateral spreading, and inertial load. In the field of designing, elastic response of piles is always a challenge for designer in liquefaction soil, by allowing deflection at top of piles. Moreover, absence of plastic hinges in piles should be insured, because the damage in the piles is not observed directly. In this study, the performance and behavior of pile foundations during liquefaction and lateral spreading are investigated. In addition, emphasize on the soil behavior in the liquefiable and non-liquefiable layers by different aspect of piles damage such as ranking, location and degree of damage are going to discuss.

Keywords: pile, earthquake, liquefaction, non-liquefiable, damage

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2081 Targeting Tumour Survival and Angiogenic Migration after Radiosensitization with an Estrone Analogue in an in vitro Bone Metastasis Model

Authors: Jolene M. Helena, Annie M. Joubert, Peace Mabeta, Magdalena Coetzee, Roy Lakier, Anne E. Mercier

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Targeting the distant tumour and its microenvironment whilst preserving bone density is important in improving the outcomes of patients with bone metastases. 2-Ethyl-3-O-sulphamoyl-estra1,3,5(10)16-tetraene (ESE-16) is an in-silico-designed 2- methoxyestradiol analogue which aimed at enhancing the parent compound’s cytotoxicity and providing a more favourable pharmacokinetic profile. In this study, the potential radiosensitization effects of ESE-16 were investigated in an in vitro bone metastasis model consisting of murine pre-osteoblastic (MC3T3-E1) and pre-osteoclastic (RAW 264.7) bone cells, metastatic prostate (DU 145) and breast (MDA-MB-231) cancer cells, as well as human umbilical vein endothelial cells (HUVECs). Cytotoxicity studies were conducted on all cell lines via spectrophotometric quantification of 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide. The experimental set-up consisted of flow cytometric analysis of cell cycle progression and apoptosis detection (Annexin V-fluorescein isothiocyanate) to determine the lowest ESE-16 and radiation doses to induce apoptosis and significantly reduce cell viability. Subsequent experiments entailed a 24-hour low-dose ESE-16-exposure followed by a single dose of radiation. Termination proceeded 2, 24 or 48 hours thereafter. The effect of the combination treatment was investigated on osteoclasts via tartrate-resistant acid phosphatase (TRAP) activity- and actin ring formation assays. Tumour cell experiments included investigation of mitotic indices via haematoxylin and eosin staining; pro-apoptotic signalling via spectrophotometric quantification of caspase 3; deoxyribonucleic acid (DNA) damage via micronuclei analysis and histone H2A.X phosphorylation (γ-H2A.X); and Western blot analyses of bone morphogenetic protein-7 and matrix metalloproteinase-9. HUVEC experiments included flow cytometric quantification of cell cycle progression and free radical production; fluorescent examination of cytoskeletal morphology; invasion and migration studies on an xCELLigence platform; and Western blot analyses of hypoxia-inducible factor 1-alpha and vascular endothelial growth factor receptor 1 and 2. Tumour cells yielded half-maximal growth inhibitory concentration (GI50) values in the nanomolar range. ESE-16 concentrations of 235 nM (DU 145) and 176 nM (MDA-MB-231) and a radiation dose of 4 Gy were found to be significant in cell cycle and apoptosis experiments. Bone and endothelial cells were exposed to the same doses as DU 145 cells. Cytotoxicity studies on bone cells reported that RAW 264.7 cells were more sensitive to the combination treatment than MC3T3-E1 cells. Mature osteoclasts were more sensitive than pre-osteoclasts with respect to TRAP activity. However, actin ring morphology was retained. The mitotic arrest was evident in tumour and endothelial cells in the mitotic index and cell cycle experiments. Increased caspase 3 activity and superoxide production indicated pro-apoptotic signalling in tumour and endothelial cells. Increased micronuclei numbers and γ-H2A.X foci indicated increased DNA damage in tumour cells. Compromised actin and tubulin morphologies and decreased invasion and migration were observed in endothelial cells. Western blot analyses revealed reduced metastatic and angiogenic signalling. ESE-16-induced radiosensitization inhibits metastatic signalling and tumour cell survival whilst preferentially preserving bone cells. This low-dose combination treatment strategy may promote the quality of life of patients with metastatic bone disease. Future studies will include 3-dimensional in-vitro and murine in-vivo models.

Keywords: angiogenesis, apoptosis, bone metastasis, cancer, cell migration, cytoskeleton, DNA damage, ESE-16, radiosensitization.

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