Search results for: site plan
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4159

Search results for: site plan

319 Ibrutinib and the Potential Risk of Cardiac Failure: A Review of Pharmacovigilance Data

Authors: Abdulaziz Alakeel, Roaa Alamri, Abdulrahman Alomair, Mohammed Fouda

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Introduction: Ibrutinib is a selective, potent, and irreversible small-molecule inhibitor of Bruton's tyrosine kinase (BTK). It forms a covalent bond with a cysteine residue (CYS-481) at the active site of Btk, leading to inhibition of Btk enzymatic activity. The drug is indicated to treat certain type of cancers such as mantle cell lymphoma (MCL), chronic lymphocytic leukaemia and Waldenström's macroglobulinaemia (WM). Cardiac failure is a condition referred to inability of heart muscle to pump adequate blood to human body organs. There are multiple types of cardiac failure including left and right-sided heart failure, systolic and diastolic heart failures. The aim of this review is to evaluate the risk of cardiac failure associated with the use of ibrutinib and to suggest regulatory recommendations if required. Methodology: Signal Detection team at the National Pharmacovigilance Center (NPC) of Saudi Food and Drug Authority (SFDA) performed a comprehensive signal review using its national database as well as the World Health Organization (WHO) database (VigiBase), to retrieve related information for assessing the causality between cardiac failure and ibrutinib. We used the WHO- Uppsala Monitoring Centre (UMC) criteria as standard for assessing the causality of the reported cases. Results: Case Review: The number of resulted cases for the combined drug/adverse drug reaction are 212 global ICSRs as of July 2020. The reviewers have selected and assessed the causality for the well-documented ICSRs with completeness scores of 0.9 and above (35 ICSRs); the value 1.0 presents the highest score for best-written ICSRs. Among the reviewed cases, more than half of them provides supportive association (four probable and 15 possible cases). Data Mining: The disproportionality of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by WHO-UMC to measure the reporting ratio. Positive IC reflects higher statistical association while negative values indicates less statistical association, considering the null value equal to zero. The results of (IC=1.5) revealed a positive statistical association for the drug/ADR combination, which means “Ibrutinib” with “Cardiac Failure” have been observed more than expected when compared to other medications available in WHO database. Conclusion: Health regulators and health care professionals must be aware for the potential risk of cardiac failure associated with ibrutinib and the monitoring of any signs or symptoms in treated patients is essential. The weighted cumulative evidences identified from causality assessment of the reported cases and data mining are sufficient to support a causal association between ibrutinib and cardiac failure.

Keywords: cardiac failure, drug safety, ibrutinib, pharmacovigilance, signal detection

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318 Pentosan Polysulfate Sodium: A Potential Treatment to Improve Bone and Joint Manifestations of Mucopolysaccharidosis I

Authors: Drago Bratkovic, Curtis Gravance, David Ketteridge, Ravi Krishnan, Michael Imperiale

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The mucopolysaccharidoses (MPSs) are a group of lysosomal storage diseases that have a common defect in the catabolism of glycosaminoglycans (GAGs). MPS I is the most common of the MPS diseases. Manifestations of MPS I include coarsening of facial features, corneal clouding, developmental delay, short stature, skeletal manifestations, hearing loss, cardiac valve disease, hepatosplenomegaly, and umbilical and inguinal hernias. Treatments for MPS I restore or activate the missing or deficient enzyme in the case of enzyme replacement therapy (ERT) and haematopoietic stem cell transplantation (HSCT). Pentosan polysulfate sodium (PPS) is a potential treatment to improve bone and joint manifestations of MPS I. The mechanisms of action of PPS that are relevant to the treatment of MPS I are the ability to: (i) Reduce systemic and accumulated GAG, (ii) Reduce inflammatory effects via the inhibition of NF-kB, resulting in the reduction in pro-inflammatory mediators. (iii) Reduce the expression of the pain mediator nerve growth factor in osteocytes from degenerating joints. (iv) Inhibit the cartilage degrading enzymes related to joint dysfunction in MPS I. PPS is being evaluated as an adjunctive therapy to ERT and/or HSCT in an open-label, single-centre, phase 2 study. Patients are ≥ 5 years of age with a diagnosis of MPS I and previously received HSCT and/or ERT. Three white, female, patients with MPS I-Hurler, ages 14, 15, and 19 years, and one, white male patient aged 15 years are enrolled. All were diagnosed at ≤2 years of age. All patients received HSCT ≤ 6 months after diagnosis. Two of the patients were treated with ERT prior to HSCT, and 1 patient received ERT commencing 3 months prior to HSCT. Two patients received 0.75mg/kg and 2 patients received 1.5mg/kg of PPS. PPS was well tolerated at doses of 0.75 and 1.5 mg/kg to 47 weeks of continuous dosing. Of the 19 adverse events (AEs), 2 were related to PPS. One AE was moderate (pre-syncope) and 1 was mild (injection site bruising), experienced in the same patient. All AEs were reported as mild or moderate. There have been no SAEs. One subject experienced a COVID-19 infection and PPS was interrupted. The MPS I signature GAG fragments, sulfated disaccharide and UA-HNAc S, tended to decrease in 3 patients from baseline through Week 25. Week 25 GAG data are pending for the 4th patient. Overall, most biomarkers (inflammatory, cartilage degeneration, and bone turnover) evaluated in the 3 patients with 25-week assessments have indicated either no change or a reduction in levels compared to baseline. In 3 patients, there was a trend toward improvement in the 2MWT from baseline to Week 48 with > 100% increase in 1 patient (01-201). In the 3 patients that had Week 48 assessments, patients and proxies reported improvement in PGIC, including “worthwhile difference” (n=1), or “made all the difference” (n=2).

Keywords: MPS I, pentosan polysulfate sodium, clinical study, 2MWT, QoL

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317 From Isolation to Integration: A Biophilic Design Approach for Enhancing Inhabitants’ Well-being in Urban Residential Spaces in Dhaka

Authors: Maliha Afroz Nitu, Shahreen Mukashafat Semontee

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The concept of biophilic design has emerged as a transformative approach to restore the intrinsic connection between people and nature, an innate bond disrupted by urbanization and industrialization. As urbanization progresses, it is crucial to raise awareness about these issues in order to ensure people can live and work in healthy environments that enhance well-being. Dhaka, the capital of Bangladesh, faces challenges arising from unplanned urban expansion, leading to a notable disconnect between city dwellers and their natural surroundings, a problem prevalent in rapidly developing megacities. Significant interdisciplinary research consistently shows that connecting indoor and outdoor spaces can improve mental and physical well-being by rekindling a connection with the natural world. However, there is a significant lack of study on the implementation of biophilic design principles in the built environment to tackle these problems, despite the well-documented advantages. The Palashi Government Staff Quarter, a 3.8-acre housing area for government staff with around 1,000 residents in Dhaka, has been selected as a case study. The main goal is to create and implement biophilic design solutions to address social, environmental, and health issues while also enhancing the built environment. A methodology applicable to improving biophilic design is developed according to the needs of the residents. This research uses a comprehensive approach, including site inspections and structured and semi-structured interviews with residents to gather qualitative data on their experiences and needs. A total of ten identical six-story buildings have been surveyed, with varying resident responses providing insight into their different perspectives. Based on these findings, the study proposes alternative design strategies that integrate biophilic elements such as daylight, air, plants, and water into buildings through windows, skylights, clerestories, green walls, vegetation, and constructed water bodies. The objective of these strategies is to improve the built environment that restores the existing disconnection between humans and nature. Comparative analyses of the current and proposed scenarios demonstrate substantial upgrades in the built environment, as well as major improvements in the physical and psychological well-being of residents. Although this research focuses on a particular government housing, the findings can be applied to other residential areas in Dhaka and similar urban environments. The study highlights the importance of biophilic design in housing and provides recommendations for policymakers and architects to improve living conditions by integrating nature into urban settings.

Keywords: biophilic design, residential, built environment, human nature connection, urban, Dhaka

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316 Study of Isoprene Emissions in Biogenic ad Anthropogenic Environment in Urban Atmosphere of Delhi: The Capital City of India

Authors: Prabhat Kashyap, Krishan Kumar

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Delhi, the capital of India, is one of the most populated and polluted city among the world. In terms of air quality, Delhi’s air is degrading day by day & becomes worst of any major city in the world. The role of biogenic volatile organic compounds (BVOCs) is not much studied in cities like Delhi as a culprit for degraded air quality. They not only play a critical role in rural areas but also determine the atmospheric chemistry of urban areas as well. Particularly, Isoprene (2-methyl 1,3-butadiene, C5H8) is the single largest emitted compound among other BVOCs globally, that influence the tropospheric ozone chemistry in urban environment as the ozone forming potential of isoprene is very high. It is mainly emitted by vegetation & a small but significant portion is also released by vehicular exhaust of petrol operated vehicles. This study investigates the spatial and temporal variations of quantitative measurements of isoprene emissions along with different traffic tracers in 2 different seasons (post-monsoon & winter) at four different locations of Delhi. For the quantification of anthropogenic and biogenic isoprene, two sites from traffic intersections (Punjabi Bagh & CRRI) and two sites from vegetative locations (JNU & Yamuna Biodiversity Park) were selected in the vicinity of isoprene emitting tree species like Ficus religiosa, Dalbergia sissoo, Eucalyptus species etc. The concentrations of traffic tracers like benzene, toluene were also determined & their robust ratios with isoprene were used to differentiate anthropogenic isoprene with biogenic portion at each site. The ozone forming potential (OFP) of all selected species along with isoprene was also estimated. For collection of intra-day samples (3 times a day) in each season, a pre-conditioned fenceline monitoring (FLM) carbopack X thermal desorption tubes were used and further analysis was done with Gas chromatography attached with mass spectrometry (GC-MS). The results of the study proposed that the ambient air isoprene is always higher in post-monsoon season as compared to winter season at all the sites because of high temperature & intense sunlight. The maximum isoprene emission flux was always observed during afternoon hours in both seasons at all sites. The maximum isoprene concentration was found to be 13.95 ppbv at Biodiversity Park during afternoon time in post monsoon season while the lower concentration was observed as low as 0.07 ppbv at the same location during morning hours in winter season. OFP of isoprene at vegetation sites is very high during post-monsoon because of high concentrations. However, OFP for other traffic tracers were high during winter seasons & at traffic locations. Furthermore, high correlation between isoprene emissions with traffic volume at traffic sites revealed that a noteworthy share of its emission also originates from road traffic.

Keywords: biogenic VOCs, isoprene emission, anthropogenic isoprene, urban vegetation

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315 Shared Vision System Support for Maintenance Tasks of Wind Turbines

Authors: Buket Celik Ünal, Onur Ünal

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Communication is the most challenging part of maintenance operations. Communication between expert and fieldworker is crucial for effective maintenance and this also affects the safety of the fieldworkers. To support a machine user in a remote collaborative physical task, both, a mobile and a stationary device are needed. Such a system is called a shared vision system and the system supports two people to solve a problem from different places. This system reduces the errors and provides a reliable support for qualified and less qualified users. Through this research, it was aimed to validate the effectiveness of using a shared vision system to facilitate communication between on-site workers and those issuing instructions regarding maintenance or inspection works over long distances. The system is designed with head-worn display which is called a shared vision system. As a part of this study, a substitute system is used and implemented by using a shared vision system for maintenance operation. The benefits of the use of a shared vision system are analyzed and results are adapted to the wind turbines to improve the occupational safety and health for maintenance technicians. The motivation for the research effort in this study can be summarized in the following research questions: -How can expert support technician over long distances during maintenance operation? -What are the advantages of using a shared vision system? Experience from the experiment shows that using a shared vision system is an advantage for both electrical and mechanical system failures. Results support that the shared vision system can be used for wind turbine maintenance and repair tasks. Because wind turbine generator/gearbox and the substitute system have similar failures. Electrical failures, such as voltage irregularities, wiring failures and mechanical failures, such as alignment, vibration, over-speed conditions are the common and similar failures for both. Furthermore, it was analyzed the effectiveness of the shared vision system by using a smart glasses in connection with the maintenance task performed by a substitute system under four different circumstances, namely by using a shared vision system, an audio communication, a smartphone and by yourself condition. A suitable method for determining dependencies between factors measured in Chi Square Test, and Chi Square Test for Independence measured for determining a relationship between two qualitative variables and finally Mann Whitney U Test is used to compare any two data sets. While based on this experiment, no relation was found between the results and the gender. Participants` responses confirmed that the shared vision system is efficient and helpful for maintenance operations. From the results of the research, there was a statistically significant difference in the average time taken by subjects on works using a shared vision system under the other conditions. Additionally, this study confirmed that a shared vision system provides reduction in time to diagnose and resolve maintenance issues, reduction in diagnosis errors, reduced travel costs for experts, and increased reliability in service.

Keywords: communication support, maintenance and inspection tasks, occupational health and safety, shared vision system

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314 Multimodal Analysis of News Magazines' Front-Page Portrayals of the US, Germany, China, and Russia

Authors: Alena Radina

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On the global stage, national image is shaped by historical memory of wars and alliances, government ideology and particularly media stereotypes which represent countries in positive or negative ways. News magazine covers are a key site for national representation. The object of analysis in this paper is the portrayals of the US, Germany, China, and Russia in the front pages and cover stories of “Time”, “Der Spiegel”, “Beijing Review”, and “Expert”. Political comedy helps people learn about current affairs even if politics is not their area of interest, and thus satire indirectly sets the public agenda. Coupled with satirical messages, cover images and the linguistic messages embedded in the covers become persuasive visual and verbal factors, known to drive about 80% of magazine sales. Preliminary analysis identified satirical elements in magazine covers, which are known to influence and frame understandings and attract younger audiences. Multimodal and transnational comparative framing analyses lay the groundwork to investigate why journalists, editors and designers deploy certain frames rather than others. This research investigates to what degree frames used in covers correlate with frames within the cover stories and what these framings can tell us about media professionals’ representations of their own and other nations. The study sample includes 32 covers consisting of two covers representing each of the four chosen countries from the four magazines. The sampling framework considers two time periods to compare countries’ representation with two different presidents, and between men and women when present. The countries selected for analysis represent each category of the international news flows model: the core nations are the US and Germany; China is a semi-peripheral country; and Russia is peripheral. Examining textual and visual design elements on the covers and images in the cover stories reveals not only what editors believe visually attracts the reader’s attention to the magazine but also how the magazines frame and construct national images and national leaders. The cover is the most powerful editorial and design page in a magazine because images incorporate less intrusive framing tools. Thus, covers require less cognitive effort of audiences who may therefore be more likely to accept the visual frame without question. Analysis of design and linguistic elements in magazine covers helps to understand how media outlets shape their audience’s perceptions and how magazines frame global issues. While previous multimodal research of covers has focused mostly on lifestyle magazines or newspapers, this paper examines the power of current affairs magazines’ covers to shape audience perception of national image.

Keywords: framing analysis, magazine covers, multimodality, national image, satire

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313 CRM Cloud Computing: An Efficient and Cost Effective Tool to Improve Customer Interactions

Authors: Gaurangi Saxena, Ravindra Saxena

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Lately, cloud computing is used to enhance the ability to attain corporate goals more effectively and efficiently at lower cost. This new computing paradigm “The Cloud Computing” has emerged as a powerful tool for optimum utilization of resources and gaining competitiveness through cost reduction and achieving business goals with greater flexibility. Realizing the importance of this new technique, most of the well known companies in computer industry like Microsoft, IBM, Google and Apple are spending millions of dollars in researching cloud computing and investigating the possibility of producing interface hardware for cloud computing systems. It is believed that by using the right middleware, a cloud computing system can execute all the programs a normal computer could run. Potentially, everything from most simple generic word processing software to highly specialized and customized programs designed for specific company could work successfully on a cloud computing system. A Cloud is a pool of virtualized computer resources. Clouds are not limited to grid environments, but also support “interactive user-facing applications” such as web applications and three-tier architectures. Cloud Computing is not a fundamentally new paradigm. It draws on existing technologies and approaches, such as utility Computing, Software-as-a-service, distributed computing, and centralized data centers. Some companies rent physical space to store servers and databases because they don’t have it available on site. Cloud computing gives these companies the option of storing data on someone else’s hardware, removing the need for physical space on the front end. Prominent service providers like Amazon, Google, SUN, IBM, Oracle, Salesforce etc. are extending computing infrastructures and platforms as a core for providing top-level services for computation, storage, database and applications. Application services could be email, office applications, finance, video, audio and data processing. By using cloud computing system a company can improve its customer relationship management. A CRM cloud computing system may be highly useful in delivering a sales team a blend of unique functionalities to improve agent/customer interactions. This paper attempts to first define the cloud computing as a tool for running business activities more effectively and efficiently at a lower cost; and then it distinguishes cloud computing with grid computing. Based on exhaustive literature review, authors discuss application of cloud computing in different disciplines of management especially in the field of marketing with special reference to use of cloud computing in CRM. Study concludes that CRM cloud computing platform helps a company track any data, such as orders, discounts, references, competitors and many more. By using CRM cloud computing, companies can improve its customer interactions and by serving them more efficiently that too at a lower cost can help gaining competitive advantage.

Keywords: cloud computing, competitive advantage, customer relationship management, grid computing

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312 In vivo Estimation of Mutation Rate of the Aleutian Mink Disease Virus

Authors: P.P. Rupasinghe, A.H. Farid

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The Aleutian mink disease virus (AMDV, Carnivore amdoparvovirus 1) causes persistent infection, plasmacytosis, and formation and deposition of immune complexes in various organs in adult mink, leading to glomerulonephritis, arteritis and sometimes death. The disease has no cure nor an effective vaccine, and identification and culling of mink positive for anti-AMDV antibodies have not been successful in controlling the infection in many countries. The failure to eradicate the virus from infected farms may be caused by keeping false-negative individuals on the farm, virus transmission from wild animals, or neighboring farms. The identification of sources of infection, which can be performed by comparing viral sequences, is important in the success of viral eradication programs. High mutation rates could cause inaccuracies when viral sequences are used to trace back an infection to its origin. There is no published information on the mutation rate of AMDV either in vivo or in vitro. The in vivo estimation is the most accurate method, but it is difficult to perform because of the inherent technical complexities, namely infecting live animals, the unknown numbers of viral generations (i.e., infection cycles), the removal of deleterious mutations over time and genetic drift. The objective of this study was to determine the mutation rate of AMDV on which no information was available. A homogenate was prepared from the spleen of one naturally infected American mink (Neovison vison) from Nova Scotia, Canada (parental template). The near full-length genome of this isolate (91.6%, 4,143 bp) was bidirectionally sequenced. A group of black mink was inoculated with this homogenate (descendant mink). Spleen sampled were collected from 10 descendant mink after 16 weeks post-inoculation (wpi) and from anther 10 mink after 176 wpi, and their near-full length genomes were bi-directionally sequenced. Sequences of these mink were compared with each other and with the sequence of the parental template. The number of nucleotide substitutions at 176 wpi was 3.1 times greater than that at 16 wpi (113 vs 36) whereas the estimates of mutation rate at 176 wpi was 3.1 times lower than that at 176 wpi (2.85×10-3 vs 9.13×10-4 substitutions/ site/ year), showing a decreasing trend in the mutation rate per unit of time. Although there is no report on in vivo estimate of the mutation rate of DNA viruses in animals using the same method which was used in the current study, these estimates are at the higher range of reported values for DNA viruses determined by various techniques. These high estimates are logical based on the wide range of diversity and pathogenicity of AMDV isolates. The results suggest that increases in the number of nucleotide substitutions over time and subsequent divergence make it difficult to accurately trace back AMDV isolates to their origin when several years elapsed between the two samplings.

Keywords: Aleutian mink disease virus, American mink, mutation rate, nucleotide substitution

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311 Fractional, Component and Morphological Composition of Ambient Air Dust in the Areas of Mining Industry

Authors: S.V. Kleyn, S.Yu. Zagorodnov, А.А. Kokoulina

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Technogenic emissions of the mining and processing complex are characterized by a high content of chemical components and solid dust particles. However, each industrial enterprise and the surrounding area have features that require refinement and parameterization. Numerous studies have shown the negative impact of fine dust PM10 and PM2.5 on the health, as well as the possibility of toxic components absorption, including heavy metals by dust particles. The target of the study was the quantitative assessment of the fractional and particle size composition of ambient air dust in the area of impact by primary magnesium production complex. Also, we tried to describe the morphology features of dust particles. Study methods. To identify the dust emission sources, the analysis of the production process has been carried out. The particulate composition of the emissions was measured using laser particle analyzer Microtrac S3500 (covered range of particle size is 20 nm to 2000 km). Particle morphology and the component composition were established by electron microscopy by scanning microscope of high resolution (magnification rate - 5 to 300 000 times) with X-ray fluorescence device S3400N ‘HITACHI’. The chemical composition was identified by X-ray analysis of the samples using an X-ray diffractometer XRD-700 ‘Shimadzu’. Determination of the dust pollution level was carried out using model calculations of emissions in the atmosphere dispersion. The calculations were verified by instrumental studies. Results of the study. The results demonstrated that the dust emissions of different technical processes are heterogeneous and fractional structure is complicated. The percentage of particle sizes up to 2.5 micrometres inclusive was ranged from 0.00 to 56.70%; particle sizes less than 10 microns inclusive – 0.00 - 85.60%; particle sizes greater than 10 microns - 14.40% -100.00%. During microscopy, the presence of nanoscale size particles has been detected. Studied dust particles are round, irregular, cubic and integral shapes. The composition of the dust includes magnesium, sodium, potassium, calcium, iron, chlorine. On the base of obtained results, it was performed the model calculations of dust emissions dispersion and establishment of the areas of fine dust РМ 10 and РМ 2.5 distribution. It was found that the dust emissions of fine powder fractions PM10 and PM2.5 are dispersed over large distances and beyond the border of the industrial site of the enterprise. The population living near the enterprise is exposed to the risk of diseases associated with dust exposure. Data are transferred to the economic entity to make decisions on the measures to minimize the risks. Exposure and risks indicators on the health are used to provide named patient health and preventive care to the citizens living in the area of negative impact of the facility.

Keywords: dust emissions, еxposure assessment, PM 10, PM 2.5

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310 Addressing Housing Issue at Regional Level Planning: A Case Study of Mumbai Metropolitan Region

Authors: Bhakti Chitale

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Mumbai city, which is the business capital of India and one of the most crowded cities in the world, holds the biggest slum in Asia. The Mumbai Metropolitan Region (MMR) occupies an area of 4035 sq.km. with a population of 22.8 million people. This population is mostly urban with 91% of this population living in areas of Municipal Corporations and Councils. Another 3% live in Census Towns. The region has 9 Municipal Corporations, 8 Municipal councils, and around 1000 villages. On the one hand MMR reflects the highest contribution to the Nations overall economy and on the other hand it shows the horrible and intolerable picture of about 2 million people, who are living in slums/without even slum with totally unhygienic conditions and with total loss of hope. The generations are about to get affected adversely if the solution is not worked out. This study is an attempt towards working out the solution. Mumbai Metropolitan Region Development Authority (MMRDA) is state government's authority, specially formed to govern the development of MMR. MMRDA is engaged in long term planning, promotion of new growth centres, implementation of strategic projects and financing infrastructure development. While preparing the master plan for MMR for next 20 years MMRDA conducted a detail study regarding Housing scenario in MMR and possible options for improvement. The author was the in charge officer for the said assignment. This paper puts light on the interesting outcomes of the research study, which ranges from the adverse effects of government policies, automatic responses of housing market, effects on planning processes, and overall changing needs of housing patterns in the world due to changes in the social mechanism. It alarms the urban planners who usually focus on smart infrastructure development, about allied future dangers. This housing study will explain the complexities, realities and needs of innovations in the housing policies all over the world. The paper will explain further few success stories and failure stories of government initiatives with reasons. It gives the clear idea about the differences in needs of housing for people from different economic groups and direct and indirect market pressures on low cost housing. Magical phenomenon came in front like a large percentage of vacant houses is present in spite of the huge need. Housing market gets affected by the developments or any other physical and financial changes taking place in the nearby areas or cities, also by changes in cities which are located far from the region and also by the international investments or policy changes. Instead of just depending on governments actions in case of generation of affordable housing, it becomes equally important to make the housing markets automatically generate such stock and still make them sustainable is the aim of all the movement. In summary, we may say that the paper will sequentially elaborate the complete dynamics of housing in one of the most crowded urban area in the world that is Mumbai Metropolitan Region, with a lot of data, analysis, case studies, and recommendations.

Keywords: Mumbai India, slum housing, region planning, market recommendations

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309 Conceptual Design of Gravity Anchor Focusing on Anchor Towing and Lowering

Authors: Vinay Kumar Vanjakula, Frank Adam, Nils Goseberg

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Wind power is one of the leading renewable energy generation methods. Due to abundant higher wind speeds far away from shore, the construction of offshore wind turbines began in the last decades. However, installation of offshore foundation-based (monopiles) wind turbines in deep waters are often associated with technical and financial challenges. To overcome such challenges, the concept of floating wind turbines is expanded as the basis from the oil and gas industry. The unfolding of Universal heavyweight gravity anchor (UGA) for floating based foundation for floating Tension Leg Platform (TLP) sub-structures is developed in this research work. It is funded by the German Federal Ministry of Education and Research) for a three-year (2019-2022) research program called “Offshore Wind Solutions Plus (OWSplus) - Floating Offshore Wind Solutions Mecklenburg-Vorpommern.” It’s a group consists of German institutions (Universities, laboratories, and consulting companies). The part of the project is focused on the numerical modeling of gravity anchor that involves to analyze and solve fluid flow problems. Compared to gravity-based torpedo anchors, these UGA will be towed and lowered via controlled machines (tug boats) at lower speeds. This kind of installation of UGA are new to the offshore wind industry, particularly for TLP, and very few research works have been carried out in recent years. Conventional methods for transporting the anchor requires a large transportation crane vessel which involves a greater cost. This conceptual UGA anchors consists of ballasting chambers which utilizes the concept of buoyancy forces; the inside chambers are filled with the required amount of water in a way that they can float on the water for towing. After reaching the installation site, those chambers are ballasted with water for lowering. After it’s lifetime, these UGA can be unballasted (for erection or replacement) results in self-rising to the sea surface; buoyancy chambers give an advantage for using an UGA without the need of heavy machinery. However, while lowering/rising the UGA towards/away from the seabed, it experiences difficult, harsh marine environments due to the interaction of waves and currents. This leads to drifting of the anchor from the desired installation position and damage to the lowering machines. To overcome such harsh environments problems, a numerical model is built to investigate the influences of different outer contours and other fluid governing shapes that can be installed on the UGA to overcome the turbulence and drifting. The presentation will highlight the importance of the Computational Fluid Dynamics (CFD) numerical model in OpenFOAM, which is open-source programming software.

Keywords: anchor lowering, towing, waves, currrents, computational fluid dynamics

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308 Stability in Slopes Related to Expansive Soils

Authors: Ivelise M. Strozberg, Lucas O. Vale, Maria V. V. Morais

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Expansive soils are characterized by their significant volumetric variations, tending to suffer an increase of this volume when added water in their voids and a decrease of volume when this water is removed. The parameters of resistance (especially the angle of friction, cohesion and specific weight) of expansive or non-expansive soils of the same field present differences, as found in laboratory tests. What is expected is that, through this research, demonstrate that this variation directly affects the results of the calculation of factors of safety for slope stability. The expansibility due to specific clay minerals such as montmorillonites and vermiculites is the most common form of expansion of soils or rocks, causing expansion pressures. These pressures can become an aggravating problem in regions across the globe that, when not previously studied, may present high risks to the enterprise, such as cracks, fissures, movements in structures, breaking of retaining walls, drilling of wells, among others. The study provides results based on analyzes carried out in the Slide 2018 software belonging to the Rocsience group, where the software is a two-dimensional equilibrium slope stability program that calculates the factor of safety or probability of failure of certain surfaces composed of soils or rocks (or both, depending on the situation), - through the methods of: Bishop simplified, Fellenius and Janbu corrected. This research compares the factors of safety of a homogeneous earthfill dam geometry, analysed for operation and end-of-construction situations, having a height of approximately 35 meters, with a slope of 1.5: 1 in the slope downstream and 2: 1 on the upstream slope. As the water level is 32.73m high and the water table is drawn automatically by the Slide program using the finite element method for the operating situation, considering two hypotheses for the use of materials - the first with soils with characteristics of expansion and the second with soils without expansibility. For this purpose, soil samples were collected from the region of São Bento do Una - Pernambuco, Brazil and taken to the soil mechanics laboratory to characterize and determine the percentage of expansibility. There were found 2 types of soils in that area: 1 site of expansive soils (8%) and another with non- expansive ones. Based on the results found, the analysis of the values of factors of safety indicated, both upstream and downstream slopes, the highest values were obtained in the case where there is no presence of materials with expansibility resulting, for one of the situations, values of 1.353 (Fellenius), 1,295 (Janbu corrected) and 1,409 (Bishop simplified). There is a considerable drop in safety factors in cases where soils are potentially expansive, resulting in values for the same situation of 0.859 (Fellenius), 0.809 (Janbu corrected) and 0.842 (Bishop simplified), in the case of higher expansibility (8 %). This shows that the expansibility is a determinant factor in the fall of resistance of soil, determined by the factors of cohesion and angle of friction.

Keywords: dam. slope. software. swelling soil

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307 Breaking the Barriers: Exploring the Barriers to LGBTQ+ Accessing Palliative Care and the Hospice

Authors: Emma Worley, Mhairi De Sainte Croix, Savneet Lochab, Christopher Roberts, Mark Stroud, Mo Salehan, Kevin Jones

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Awareness about the importance of teaching about diversity at medical school is growing. In the realm of diversity includes discussion around the LGBTQ+ community. At Bristol, diversity is taught in first or second year. However, echoing and expanding that teaching throughout the curriculum is needed. This feeds into the spiral curriculum but also highlights the relevance of the topic. It is well known that some people in the LGBTQ+ community struggle the access healthcare due to previous negative experiences. In 2019, 1 in 7 LGBTQ+ people avoided seeking medical care due to fears about discrimination. If people have fears about seeking medical help, then seeking help from Palliative care when they are at their most vulnerable situation can be even harder. To improve positive healthcare situations for people who identify as LGBTQ+ needs to start with talking. Along with some of our CTAs (clinical teaching assistants) we created a teaching session to explore the barriers faced by LGBTQ+ and incorporated communication stations into this. Our plan is to run this session as a three-hour session first discussing different topics: ethnical diversity, ‘coming out’, LGBTQ+ in the older generation, transgender. This will be followed by looking more closely at the barriers to accessing the hospice. The next part of the session will encompass two or three communication scenarios hopefully prompting further discussion and reflection on ways to improve our communication. The first scenario outline is a gay man/lesbian woman with lung cancer discussing options around the hospice. The second scenario is a transgender person with female genitalia who now has cervical cancer (as was not followed up on pap smears after the change of name). The third scenario is a HIV homosexual male patient who has been admitted with dementia. He has a partner but is not married. His next of kin is down as his parents but his parents do not know about his sexuality and HIV status. It allows discussion around confidentiality as well as broaching the meaning of ‘family’ in the LGBTQ+ community. We have chosen to pitch this teaching session to Bristol Year 4 students. They will be currently doing their 6-week Palliative care block, which fits in well. Each session will have four students attend. We have been lucky enough to have two CTAs (clinical teaching assistants) who identify as LGBTQ+ offer their experiences and help. They have been able to help us with the preparation and delivery of the session. Given anecdotal evidence and stories helps to highlight the importance and relevance of this session. The aim is to increase awareness of some factors that may contribute to people who identify as LGBTQ+ having a negative healthcare experience. By starting to talk about it allows awareness and only then will we be able to start to change and improve. Our aim, if the sessions run well, is to expand these sessions to different academy hospitals. Therefore, all Bristol 4th year students would have the opportunity to take part in the teaching session. We would like to expand our portfolio of case scenarios, to address so tricker topics such as a transgender person with dementia who reverts back to a different gender. We would also like to recruit a diverse range of actors, ideally people who identify as the patient in the scenario does. For example, a transgender person acts the transgender scenario. This would give authenticity and enhance the student’s learning experience.

Keywords: communication skills, healthcare barriers, LGBTQ+, palliative care

Procedia PDF Downloads 124
306 Introduction of Acute Paediatric Services in Primary Care: Evaluating the Impact on GP Education

Authors: Salman Imran, Chris Healey

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Traditionally, medical care of children in England and Wales starts from primary care with a referral to secondary care paediatricians who may not investigate further. Many primary care doctors do not undergo a paediatric rotation/exposure in training. As a result, there are many who have not acquired the necessary skills to manage children hence increasing hospital referral. With the current demand on hospitals in the National Health Service managing more problems in the community is needed. One way of handling this is to set up clinics, meetings and huddles in GP surgeries where professionals involved (general practitioner, paediatrician, health visitor, community nurse, dietician, school nurse) come together and share information which can help improve communication and care. The increased awareness and education that paediatricians can impart in this way will help boost confidence for primary care professionals to be able to be more self-sufficient. This has been tried successfully in other regions e.g., St. Mary’s Hospital in London but is crucial for a more rural setting like ours. The primary aim of this project would be to educate specifically GP’s and generally all other health professionals involved. Additional benefits would be providing care nearer home, increasing patient’s confidence in their local surgery, improving communication and reducing unnecessary patient flow to already stretched hospital resources. Methods: This was done as a plan do study act cycle (PDSA). Three clinics were delivered in different practices over six months where feedback from staff and patients was collected. Designated time for teaching/discussion was used which involved some cases from the actual clinics. Both new and follow up patients were included. Two clinics were conducted by a paediatrician and nurse whilst the 3rd involved paediatrician and local doctor. The distance from hospital to clinics varied from two miles to 22 miles approximately. All equipment used was provided by primary care. Results: A total of 30 patients were seen. All patients found the location convenient as it was nearer than the hospital. 70-90% clearly understood the reason for a change in venue. 95% agreed to the importance of their local doctor being involved in their care. 20% needed to be seen in the hospital for further investigations. Patients felt this to be a more personalised, in-depth, friendly and polite experience. Local physicians felt this to be a more relaxed, familiar and local experience for their patients and they managed to get immediate feedback regarding their own clinical management. 90% felt they gained important learning from the discussion time and the paediatrician also learned about their understanding and gaps in knowledge/focus areas. 80% felt this time was valuable for targeted learning. Equipment, information technology, and office space could be improved for the smooth running of any future clinics. Conclusion: The acute paediatric outpatient clinic can be successfully established in primary care facilities. Careful patient selection and adequate facilities are important. We have demonstrated a further step in the reduction of patient flow to hospitals and upskilling primary care health professionals. This service is expected to become more efficient with experience.

Keywords: clinics, education, paediatricians, primary care

Procedia PDF Downloads 161
305 A Hybrid of BioWin and Computational Fluid Dynamics Based Modeling of Biological Wastewater Treatment Plants for Model-Based Control

Authors: Komal Rathore, Kiesha Pierre, Kyle Cogswell, Aaron Driscoll, Andres Tejada Martinez, Gita Iranipour, Luke Mulford, Aydin Sunol

Abstract:

Modeling of Biological Wastewater Treatment Plants requires several parameters for kinetic rate expressions, thermo-physical properties, and hydrodynamic behavior. The kinetics and associated mechanisms become complex due to several biological processes taking place in wastewater treatment plants at varying times and spatial scales. A dynamic process model that incorporated the complex model for activated sludge kinetics was developed using the BioWin software platform for an Advanced Wastewater Treatment Plant in Valrico, Florida. Due to the extensive number of tunable parameters, an experimental design was employed for judicious selection of the most influential parameter sets and their bounds. The model was tuned using both the influent and effluent plant data to reconcile and rectify the forecasted results from the BioWin Model. Amount of mixed liquor suspended solids in the oxidation ditch, aeration rates and recycle rates were adjusted accordingly. The experimental analysis and plant SCADA data were used to predict influent wastewater rates and composition profiles as a function of time for extended periods. The lumped dynamic model development process was coupled with Computational Fluid Dynamics (CFD) modeling of the key units such as oxidation ditches in the plant. Several CFD models that incorporate the nitrification-denitrification kinetics, as well as, hydrodynamics was developed and being tested using ANSYS Fluent software platform. These realistic and verified models developed using BioWin and ANSYS were used to plan beforehand the operating policies and control strategies for the biological wastewater plant accordingly that further allows regulatory compliance at minimum operational cost. These models, with a little bit of tuning, can be used for other biological wastewater treatment plants as well. The BioWin model mimics the existing performance of the Valrico Plant which allowed the operators and engineers to predict effluent behavior and take control actions to meet the discharge limits of the plant. Also, with the help of this model, we were able to find out the key kinetic and stoichiometric parameters which are significantly more important for modeling of biological wastewater treatment plants. One of the other important findings from this model were the effects of mixed liquor suspended solids and recycle ratios on the effluent concentration of various parameters such as total nitrogen, ammonia, nitrate, nitrite, etc. The ANSYS model allowed the abstraction of information such as the formation of dead zones increases through the length of the oxidation ditches as compared to near the aerators. These profiles were also very useful in studying the behavior of mixing patterns, effect of aerator speed, and use of baffles which in turn helps in optimizing the plant performance.

Keywords: computational fluid dynamics, flow-sheet simulation, kinetic modeling, process dynamics

Procedia PDF Downloads 205
304 Foreseen the Future: Human Factors Integration in European Horizon Projects

Authors: José Manuel Palma, Paula Pereira, Margarida Tomás

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Foreseen the future: Human factors integration in European Horizon Projects The development of new technology as artificial intelligence, smart sensing, robotics, cobotics or intelligent machinery must integrate human factors to address the need to optimize systems and processes, thereby contributing to the creation of a safe and accident-free work environment. Human Factors Integration (HFI) consistently pose a challenge for organizations when applied to daily operations. AGILEHAND and FORTIS projects are grounded in the development of cutting-edge technology - industry 4.0 and 5.0. AGILEHAND aims to create advanced technologies for autonomously sort, handle, and package soft and deformable products, whereas FORTIS focuses on developing a comprehensive Human-Robot Interaction (HRI) solution. Both projects employ different approaches to explore HFI. AGILEHAND is mainly empirical, involving a comparison between the current and future work conditions reality, coupled with an understanding of best practices and the enhancement of safety aspects, primarily through management. FORTIS applies HFI throughout the project, developing a human-centric approach that includes understanding human behavior, perceiving activities, and facilitating contextual human-robot information exchange. it intervention is holistic, merging technology with the physical and social contexts, based on a total safety culture model. In AGILEHAND we will identify safety emergent risks, challenges, their causes and how to overcome them by resorting to interviews, questionnaires, literature review and case studies. Findings and results will be presented in “Strategies for Workers’ Skills Development, Health and Safety, Communication and Engagement” Handbook. The FORTIS project will implement continuous monitoring and guidance of activities, with a critical focus on early detection and elimination (or mitigation) of risks associated with the new technology, as well as guidance to adhere correctly with European Union safety and privacy regulations, ensuring HFI, thereby contributing to an optimized safe work environment. To achieve this, we will embed safety by design, and apply questionnaires, perform site visits, provide risk assessments, and closely track progress while suggesting and recommending best practices. The outcomes of these measures will be compiled in the project deliverable titled “Human Safety and Privacy Measures”. These projects received funding from European Union’s Horizon 2020/Horizon Europe research and innovation program under grant agreement No101092043 (AGILEHAND) and No 101135707 (FORTIS).

Keywords: human factors integration, automation, digitalization, human robot interaction, industry 4.0 and 5.0

Procedia PDF Downloads 57
303 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

Procedia PDF Downloads 364
302 Application of 2D Electrical Resistivity Tomographic Imaging Technique to Study Climate Induced Landslide and Slope Stability through the Analysis of Factor of Safety: A Case Study in Ooty Area, Tamil Nadu, India

Authors: S. Maniruzzaman, N. Ramanujam, Qazi Akhter Rasool, Swapan Kumar Biswas, P. Prasad, Chandrakanta Ojha

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Landslide is one of the major natural disasters in South Asian countries. Applying 2D Electrical Resistivity Tomographic Imaging estimation of geometry, thickness, and depth of failure zone of the landslide can be made. Landslide is a pertinent problem in Nilgris plateau next to Himalaya. Nilgris range consists of hard Archean metamorphic rocks. Intense weathering prevailed during the Pre-Cambrian time had deformed the rocks up to 45m depth. The landslides are dominant in the southern and eastern part of plateau of is comparatively smaller than the northern drainage basins, as it has low density of drainage; coarse texture permitted the more of infiltration of rainwater, whereas in the northern part of the plateau entombed with high density of drainage pattern and fine texture with less infiltration than run off, and low to the susceptible to landslide. To get comprehensive information about the landslide zone 2D Electrical Resistivity Tomographic imaging study with CRM 500 Resistivity meter are used in Coonoor– Mettupalyam sector of Nilgiris plateau. To calculate Factor of Safety the infinite slope model of Brunsden and Prior is used. Factor of Safety can be expressed (FS) as the ratio of resisting forces to disturbing forces. If FS < 1 disturbing forces are larger than resisting forces and failure may occur. The geotechnical parameters of soil samples are calculated on the basis upon the apparent resistivity values for litho units of measured from 2D ERT image of the landslide zone. Relationship between friction angles for various soil properties is established by simple regression analysis from apparent resistivity data. Increase of water content in slide zone reduces the effectiveness of the shearing resistance and increase the sliding movement. Time-lapse resistivity changes to slope failure is determined through geophysical Factor of Safety which depends on resistivity and site topography. This ERT technique infers soil property at variable depths in wider areas. This approach to retrieve the soil property and overcomes the limit of the point of information provided by rain gauges and porous probes. Monitoring of slope stability without altering soil structure through the ERT technique is non-invasive with low cost. In landslide prone area an automated Electrical Resistivity Tomographic Imaging system should be installed permanently with electrode networks to monitor the hydraulic precursors to monitor landslide movement.

Keywords: 2D ERT, landslide, safety factor, slope stability

Procedia PDF Downloads 312
301 Geomorphology and Flood Analysis Using Light Detection and Ranging

Authors: George R. Puno, Eric N. Bruno

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The natural landscape of the Philippine archipelago plus the current realities of climate change make the country vulnerable to flood hazards. Flooding becomes the recurring natural disaster in the country resulting to lose of lives and properties. Musimusi is among the rivers which exhibited inundation particularly at the inhabited floodplain portion of its watershed. During the event, rescue operations and distribution of relief goods become a problem due to lack of high resolution flood maps to aid local government unit identify the most affected areas. In the attempt of minimizing impact of flooding, hydrologic modelling with high resolution mapping is becoming more challenging and important. This study focused on the analysis of flood extent as a function of different geomorphologic characteristics of Musimusi watershed. The methods include the delineation of morphometric parameters in the Musimusi watershed using Geographic Information System (GIS) and geometric calculations tools. Digital Terrain Model (DTM) as one of the derivatives of Light Detection and Ranging (LiDAR) technology was used to determine the extent of river inundation involving the application of Hydrologic Engineering Center-River Analysis System (HEC-RAS) and Hydrology Modelling System (HEC-HMS) models. The digital elevation model (DEM) from synthetic Aperture Radar (SAR) was used to delineate watershed boundary and river network. Datasets like mean sea level, river cross section, river stage, discharge and rainfall were also used as input parameters. Curve number (CN), vegetation, and soil properties were calibrated based on the existing condition of the site. Results showed that the drainage density value of the watershed is low which indicates that the basin is highly permeable subsoil and thick vegetative cover. The watershed’s elongation ratio value of 0.9 implies that the floodplain portion of the watershed is susceptible to flooding. The bifurcation ratio value of 2.1 indicates higher risk of flooding in localized areas of the watershed. The circularity ratio value (1.20) indicates that the basin is circular in shape, high discharge of runoff and low permeability of the subsoil condition. The heavy rainfall of 167 mm brought by Typhoon Seniang last December 29, 2014 was characterized as high intensity and long duration, with a return period of 100 years produced 316 m3s-1 outflows. Portion of the floodplain zone (1.52%) suffered inundation with 2.76 m depth at the maximum. The information generated in this study is helpful to the local disaster risk reduction management council in monitoring the affected sites for more appropriate decisions so that cost of rescue operations and relief goods distribution is minimized.

Keywords: flooding, geomorphology, mapping, watershed

Procedia PDF Downloads 229
300 Digital Twins in the Built Environment: A Systematic Literature Review

Authors: Bagireanu Astrid, Bros-Williamson Julio, Duncheva Mila, Currie John

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Digital Twins (DT) are an innovative concept of cyber-physical integration of data between an asset and its virtual replica. They have originated in established industries such as manufacturing and aviation and have garnered increasing attention as a potentially transformative technology within the built environment. With the potential to support decision-making, real-time simulations, forecasting abilities and managing operations, DT do not fall under a singular scope. This makes defining and leveraging the potential uses of DT a potential missed opportunity. Despite its recognised potential in established industries, literature on DT in the built environment remains limited. Inadequate attention has been given to the implementation of DT in construction projects, as opposed to its operational stage applications. Additionally, the absence of a standardised definition has resulted in inconsistent interpretations of DT in both industry and academia. There is a need to consolidate research to foster a unified understanding of the DT. Such consolidation is indispensable to ensure that future research is undertaken with a solid foundation. This paper aims to present a comprehensive systematic literature review on the role of DT in the built environment. To accomplish this objective, a review and thematic analysis was conducted, encompassing relevant papers from the last five years. The identified papers are categorised based on their specific areas of focus, and the content of these papers was translated into a through classification of DT. In characterising DT and the associated data processes identified, this systematic literature review has identified 6 DT opportunities specifically relevant to the built environment: Facilitating collaborative procurement methods, Supporting net-zero and decarbonization goals, Supporting Modern Methods of Construction (MMC) and off-site manufacturing (OSM), Providing increased transparency and stakeholders collaboration, Supporting complex decision making (real-time simulations and forecasting abilities) and Seamless integration with Internet of Things (IoT), data analytics and other DT. Finally, a discussion of each area of research is provided. A table of definitions of DT across the reviewed literature is provided, seeking to delineate the current state of DT implementation in the built environment context. Gaps in knowledge are identified, as well as research challenges and opportunities for further advancements in the implementation of DT within the built environment. This paper critically assesses the existing literature to identify the potential of DT applications, aiming to harness the transformative capabilities of data in the built environment. By fostering a unified comprehension of DT, this paper contributes to advancing the effective adoption and utilisation of this technology, accelerating progress towards the realisation of smart cities, decarbonisation, and other envisioned roles for DT in the construction domain.

Keywords: built environment, design, digital twins, literature review

Procedia PDF Downloads 74
299 A Randomized Active Controlled Clinical Trial to Assess Clinical Efficacy and Safety of Tapentadol Nasal Spray in Moderate to Severe Post-Surgical Pain

Authors: Kamal Tolani, Sandeep Kumar, Rohit Luthra, Ankit Dadhania, Krishnaprasad K., Ram Gupta, Deepa Joshi

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Background: Post-operative analgesia remains a clinical challenge, with central and peripheral sensitization playing a pivotal role in treatment-related complications and impaired quality of life. Centrally acting opioids offer poor risk benefit profile with increased intensity of gastrointestinal or central side effects and slow onset of clinical analgesia. The objective of this study was to assess the clinical feasibility of induction and maintenance therapy with Tapentadol Nasal Spray (NS) in moderate to severe acute post-operative pain. Methods: Phase III, randomized, active-controlled, non-inferiority clinical trial involving 294 cases who had undergone surgical procedures under general anesthesia or regional anesthesia. Post-surgery patients were randomized to receive either Tapentadol NS 45 mg or Tramadol 100mg IV as a bolus and subsequent 50 mg or 100 mg dose over 2-3 minutes. The frequency of administration of NS was at every 4-6 hours. At the end of 24 hrs, patients in the tramadol group who had a pain intensity score of ≥4 were switched to oral tramadol immediate release 100mg capsule until the pain intensity score reduced to <4. All patients who had achieved pain intensity ≤ 4 were shifted to a lower dose of either Tapentadol NS 22.5 mg or oral Tramadol immediate release 50mg capsule. The statistical analysis plan was envisaged as a non-inferiority trial involving comparison with Tramadol for Pain intensity difference at 60 minutes (PID60min), Sum of Pain intensity difference at 60 minutes (SPID60min), and Physician Global Assessment at 24 hrs (PGA24 hrs). Results: The per-protocol analyses involved 255 hospitalized cases undergoing surgical procedures. The median age of patients was 38.0 years. For the primary efficacy variables, Tapentadol NS was non-inferior to Inj/Oral Tramadol in relief of moderate to severe post-operative pain. On the basis of SPID60min, no clinically significant difference was observed between Tapentadol NS and Tramadol IV (1.73±2.24 vs. 1.64± 1.92, -0.09 [95% CI, -0.43, 0.60]). In the co-primary endpoint PGA24hrs, Tapentadol NS was non–inferior to Tramadol IV (2.12 ± 0.707 vs. 2.02 ±0.704, - 0.11[95% CI, -0.07, 0.28). However, on further assessment at 48hr, 72 hrs, and 120hrs, clinically superior pain relief was observed with the Tapentadol NS formulation that was statistically significant (p <0.05) at each of the time intervals. Secondary efficacy measures, including the onset of clinical analgesia and TOTPAR, showed non-inferiority to Tramadol. The safety profile and need for rescue medication were also similar in both the groups during the treatment period. The most common concomitant medications were anti-bacterial (98.3%). Conclusion: Tapentadol NS is a clinically feasible option for improved compliance as induction and maintenance therapy while offering a sustained and persistent patient response that is clinically meaningful in post-surgical settings.

Keywords: tapentadol nasal spray, acute pain, tramadol, post-operative pain

Procedia PDF Downloads 242
298 Bioactive Substances-Loaded Water-in-Oil/Oil-in-Water Emulsions for Dietary Supplementation in the Elderly

Authors: Agnieszka Markowska-Radomska, Ewa Dluska

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Maintaining a bioactive substances dense diet is important for the elderly, especially to prevent diseases and to support healthy ageing. Adequate bioactive substances intake can reduce the risk of developing chronic diseases (e.g. cardiovascular, osteoporosis, neurodegenerative syndromes, diseases of the oral cavity, gastrointestinal (GI) disorders, diabetes, and cancer). This can be achieved by introducing a comprehensive supplementation of components necessary for the proper functioning of the ageing body. The paper proposes the multiple emulsions of the W1/O/W2 (water-in-oil-in-water) type as carriers for effective co-encapsulation and co-delivery of bioactive substances in supplementation of the elderly. Multiple emulsions are complex structured systems ("drops in drops"). The functional structure of the W1/O/W2 emulsion enables (i) incorporation of one or more bioactive components (lipophilic and hydrophilic); (ii) enhancement of stability and bioavailability of encapsulated substances; (iii) prevention of interactions between substances, as well as with the external environment, delivery to a specific location; and (iv) release in a controlled manner. The multiple emulsions were prepared by a one-step method in the Couette-Taylor flow (CTF) contactor in a continuous manner. In general, a two-step emulsification process is used to obtain multiple emulsions. The paper contains a proposal of emulsion functionalization by introducing pH-responsive biopolymer—carboxymethylcellulose sodium salt (CMC-Na) to the external phase, which made it possible to achieve a release of components controlled by the pH of the gastrointestinal environment. The membrane phase of emulsions was soybean oil. The W1/O/W2 emulsions were evaluated for their characteristics (drops size/drop size distribution, volume packing fraction), encapsulation efficiency and stability during storage (to 30 days) at 4ºC and 25ºC. Also, the in vitro multi-substance co-release process were investigated in a simulated gastrointestinal environment (different pH and composition of release medium). Three groups of stable multiple emulsions were obtained: emulsions I with co-encapsulated vitamins B12, B6 and resveratrol; emulsions II with vitamin A and β-carotene; and emulsions III with vitamins C, E and D3. The substances were encapsulated in the appropriate emulsion phases depending on the solubility. For all emulsions, high encapsulation efficience (over 95%) and high volume packing fraction of internal droplets (0.54-0.76) were reached. In addition, due to the presence of a polymer (CMC-Na) with adhesive properties, high encapsulation stability during emulsions storage were achieved. The co-release study of encapsulated bioactive substances confirmed the possibility to modify the release profiles. It was found that the releasing process can be controlled through the composition, structure, physicochemical parameters of emulsions and pH of the release medium. The results showed that the obtained multiple emulsions might be used as potential liquid complex carriers for controlled/modified/site-specific co-delivery of bioactive substances in dietary supplementation in the elderly.

Keywords: bioactive substance co-release, co-encapsulation, elderly supplementation, multiple emulsion

Procedia PDF Downloads 194
297 Journeys of Healing for Military Veterans: A Pilot Study

Authors: Heather Warfield, Brad Genereux

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Military personnel encounter a number of challenges when separating from military service to include career uncertainty, relational/family dynamics, trauma as a result of military experiences, reconceptualization of identity, and existential issues related to purpose, meaning making and framing of the military experience(s). Embedded within military culture are well-defined rites of passage and a significant sense of belonging. Consequently, transition out of the military can result in the loss of such rites of passage and belongingness. However, a pilgrimage journey can provide the time and space to engage in a new rite of passage, to construct a new pilgrim identity, and a to develop deep social relationships that lead to a sense of belongingness to a particular pilgrim community as well as to the global community of pilgrims across numerous types of pilgrimage journeys. The aims of the current paper are to demonstrate the rationale for why pilgrimage journeys are particularly significant for military veterans, provide an overview of an innovative program that facilitates the Camino de Santiago pilgrimage for military veterans, and discusses the lessons learned from the initial pilot project of a recently established program. Veterans on the Camino (VOC) is an emerging nongovernmental organization in the USA. Founded by a military veteran, after leaving his military career, the primary objective of the organization is to facilitate healing for veterans via the Camino de Santiago pilgrimage journey. As part of the program, participants complete a semi-structured interview at three time points – pre, during, and post journey. The interview items are based on ongoing research by the principal investigator and address such constructs as meaning-making, wellbeing, therapeutic benefits and transformation. In addition, program participants complete The Sources of Meaning and Meaning in Life Questionnaire (SoMe). The pilot program occurred in the spring of 2017. Five participants were selected after an extensive application process and review by a three-person selection board. The selection criteria included demonstrated compatibility with the program objectives (i.e., prior military experience, availability for a 40 day journey, and awareness of the need for a transformational intervention). The participants were connected as a group through a private Facebook site and interacted with one another for several months prior to the pilgrimage. Additionally, the participants were interviewed prior to beginning the pilgrimage, at one point during the pilgrimage and immediately following the conclusion of the pilgrimage journey. The interviews yielded themes related to loss, meaning construction, renewed hope in humanity, and a commitment to future goals. The lessons learned from this pilot project included a confirmation of the need for such a program, a need for greater focus on logistical details, and the recognition that the pilgrimage experience needs to continue in some manner once the veterans return home.

Keywords: pilgrimage, healing, military veterans, Camino de Santiago

Procedia PDF Downloads 287
296 A Research on the Effect of Soil-Structure Interaction on the Dynamic Response of Symmetrical Reinforced Concrete Buildings

Authors: Adinew Gebremeskel Tizazu

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The effect of soil-structure interaction on the dynamic response of reinforced concrete buildings of regular and symmetrical geometry are considered in this study. The structures are presumed to be generally embedded in a homogenous soil formation underlain by very stiff material or bedrock. The structure-foundation–soil system is excited at the base by an earthquake ground motion. The superstructure is idealized as a system with lumped masses concentrated at the floor levels, and coupled with the substructure. The substructure system, which comprises of the foundation and soil, is represented, and replaced by springs and dashpots. Frequency-dependent impedances of the foundation system are incorporated in the discrete model in terms of the springs and dashpots coefficients. The excitation applied to the model is field ground motions of actual earthquake records. Modal superposition principle is employed to transform the equations of motion in geometrical coordinates to modal coordinates. However, the modal equations remain coupled with respect to damping terms due to the difference in damping mechanisms of the superstructure and the soil. Hence, proportional damping for the coupled structural system may not be assumed. An iterative approach is adopted and programmed to solve the system of coupled equations of motion in modal coordinates to obtain the displacement responses of the system. Parametric studies for responses of building structures with regular and symmetric plans of different structural properties and heights are made for fixed and flexible base conditions, for different soil conditions encountered in Addis Ababa. The displacement, base shear and base overturning moments are used in the comparison of different types of structures for various foundation embedment depths, site conditions and height of structures. These values are compared against those of fixed base structure. The study shows that the flexible base structures, generally exhibit different responses from those structures with fixed base. Basically, the natural circular frequencies, the base shears and the inter-story displacements for the flexible base are less than those of the fixed base structures. This trend is particularly evident when the flexible soil has large thickness. In contrast, the trend becomes less predictable, when the thickness of the flexible soil decreases. Moreover, in the latter case, the iteration undulates significantly making the prediction difficult. This is attributed to the highly jagged nature of the impedance functions of frequencies for such formations. In this case, it is difficult to conclude whether the conventional fixed-base approach yields conservative design forces, as is the case for soil formations of large thickness.

Keywords: effect of soil structure, dynamic response corroborated, the modal superposition principle, parametric studies

Procedia PDF Downloads 27
295 ENDO-β-1,4-Xylanase from Thermophilic Geobacillus stearothermophilus: Immobilization Using Matrix Entrapment Technique to Increase the Stability and Recycling Efficiency

Authors: Afsheen Aman, Zainab Bibi, Shah Ali Ul Qader

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Introduction: Xylan is a heteropolysaccharide composed of xylose monomers linked together through 1,4 linkages within a complex xylan network. Owing to wide applications of xylan hydrolytic products (xylose, xylobiose and xylooligosaccharide) the researchers are focusing towards the development of various strategies for efficient xylan degradation. One of the most important strategies focused is the use of heat tolerant biocatalysts which acts as strong and specific cleaving agents. Therefore, the exploration of microbial pool from extremely diversified ecosystem is considerably vital. Microbial populations from extreme habitats are keenly explored for the isolation of thermophilic entities. These thermozymes usually demonstrate fast hydrolytic rate, can produce high yields of product and are less prone to microbial contamination. Another possibility of degrading xylan continuously is the use of immobilization technique. The current work is an effort to merge both the positive aspects of thermozyme and immobilization technique. Methodology: Geobacillus stearothermophilus was isolated from soil sample collected near the blast furnace site. This thermophile is capable of producing thermostable endo-β-1,4-xylanase which cleaves xylan effectively. In the current study, this thermozyme was immobilized within a synthetic and a non-synthetic matrice for continuous production of metabolites using entrapment technique. The kinetic parameters of the free and immobilized enzyme were studied. For this purpose calcium alginate and polyacrylamide beads were prepared. Results: For the synthesis of immobilized beads, sodium alginate (40.0 gL-1) and calcium chloride (0.4 M) was used amalgamated. The temperature (50°C) and pH (7.0) optima of immobilized enzyme remained same for xylan hydrolysis however, the enzyme-substrate catalytic reaction time raised from 5.0 to 30.0 minutes as compared to free counterpart. Diffusion limit of high molecular weight xylan (corncob) caused a decline in Vmax of immobilized enzyme from 4773 to 203.7 U min-1 whereas, Km value increased from 0.5074 to 0.5722 mg ml-1 with reference to free enzyme. Immobilized endo-β-1,4-xylanase showed its stability at high temperatures as compared to free enzyme. It retained 18% and 9% residual activity at 70°C and 80°C, respectively whereas; free enzyme completely lost its activity at both temperatures. The Immobilized thermozyme displayed sufficient recycling efficiency and can be reused up to five reaction cycles, indicating that this enzyme can be a plausible candidate in paper processing industry. Conclusion: This thermozyme showed better immobilization yield and operational stability with the purpose of hydrolyzing the high molecular weight xylan. However, the enzyme immobilization properties can be improved further by immobilizing it on different supports for industrial purpose.

Keywords: immobilization, reusability, thermozymes, xylanase

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294 Clinical Response of Nuberol Forte® (Paracetamol 650 MG+Orphenadrine 50 MG) For Pain Management with Musculoskeletal Conditions in Routine Pakistani Practice (NFORTE-EFFECT)

Authors: Shahid Noor, Kazim Najjad, Muhammad Nasir, Irshad Bhutto, Abdul Samad Memon, Khurram Anwar, Tehseen Riaz, Mian Muhammad Hanif, Nauman A. Mallik, Saeed Ahmed, Israr Ahmed, Ali Yasir

Abstract:

Background: Musculoskeletal pain is the most common complaint presented to the health practitioner. It is well known that untreated or under-treated pain can have a significant negative impact on an individual’s quality of life (QoL). Objectives: This study was conducted across 10 sites in six (6) major cities of Pakistan to evaluate the tolerability, safety, and the clinical response of Nuberol Forte® (Paracetamol 650 mg + Orphenadrine 50 mg) to musculoskeletal pain in routine Pakistani practice and its impact on improving the patient’s QoL. Design & Methods: This NFORT-EFFECT observational, prospective multicenter study was conducted in compliance with Good Clinical Practice guidelines and local regulatory requirements. The study sponsor was "The Searle Company Limited, Pakistan. To maintain the GCP compliances, the sponsor assigned the CRO for the site and data management. Ethical approval was obtained from an independent ethics committee. The IEC reviewed the progress of the study. Written informed consent was obtained from the study participants, and their confidentiality was maintained throughout the study. A total of 399 patients with known prescreened musculoskeletal conditions and pain who attended the study sites were recruited, as per the inclusion/exclusion criteria (clinicaltrials.gov ID# NCT04765787). The recruited patients were then prescribed Paracetamol (650 mg) and Orphenadrine (50 mg) combination (Nuberol Forte®) for 7 to 14 days as per the investigator's discretion based on the pain intensity. After the initial screening (visit 1), a follow-up visit was conducted after 1-2 weeks of the treatment (visit 2). Study Endpoints: The primary objective was to assess the pain management response of Nuberol Forte treatment and the overall safety of the drug. The Visual Analogue Scale (VAS) scale was used to measure pain severity. Secondary to pain, the patients' health-related quality of life (HRQoL) was also assessed using the Muscle, Joint Measure (MJM) scale. The safety was monitored on the first dose by the patients. These assessments were done on each study visit. Results: Out of 399 enrolled patients, 49.4% were males, and 50.6% were females with a mean age of 47.24 ± 14.20 years. Most patients were presented with Knee Osteoarthritis (OA), i.e., 148(38%), followed by backache 70(18.2%). A significant reduction in the mean pain score was observed after the treatment with the combination of Paracetamol and Orphenadrine (p<0.05). Furthermore, an overall improvement in the patient’s QoL was also observed. During the study, only ten patients reported mild adverse events (AEs). Conclusion: The combination of Paracetamol and Orphenadrine (Nuberol Forte®) exhibited effective pain management among patients with musculoskeletal conditions and also improved their QoL.

Keywords: musculoskeletal pain, orphenadrine/paracetamol combination, pain management, quality of life, Pakistani population

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293 The Impact of Reducing Road Traffic Speed in London on Noise Levels: A Comparative Study of Field Measurement and Theoretical Calculation

Authors: Jessica Cecchinelli, Amer Ali

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The continuing growth in road traffic and the resultant impact on the level of pollution and safety especially in urban areas have led local and national authorities to reduce traffic speed and flow in major towns and cities. Various boroughs of London have recently reduced the in-city speed limit from 30mph to 20mph mainly to calm traffic, improve safety and reduce noise and vibration. This paper reports the detailed field measurements using noise sensor and analyser and the corresponding theoretical calculations and analysis of the noise levels on a number of roads in the central London Borough of Camden where speed limit was reduced from 30mph to 20mph in all roads except the major routes of the ‘Transport for London (TfL)’. The measurements, which included the key noise levels and scales at residential streets and main roads, were conducted during weekdays and weekends normal and rush hours. The theoretical calculations were done according to the UK procedure ‘Calculation of Road Traffic Noise 1988’ and with conversion to the European L-day, L-evening, L-night, and L-den and other important levels. The current study also includes comparable data and analysis from previously measured noise in the Borough of Camden and other boroughs of central London. Classified traffic flow and speed on the roads concerned were observed and used in the calculation part of the study. Relevant data and description of the weather condition are reported. The paper also reports a field survey in the form of face-to-face interview questionnaires, which was carried out in parallel with the field measurement of noise, in order to ascertain the opinions and views of local residents and workers in the reduced speed zones of 20mph. The main findings are that the reduction in speed had reduced the noise pollution on the studied zones and that the measured and calculated noise levels for each speed zone are closely matched. Among the other findings was that of the field survey of the opinions and views of the local residents and workers in the reduced speed 20mph zones who supported the scheme and felt that it had improved the quality of life in their areas giving a sense of calmness and safety particularly for families with children, the elderly, and encouraged pedestrians and cyclists. The key conclusions are that lowering the speed limit in built-up areas would not just reduce the number of serious accidents but it would also reduce the noise pollution and promote clean modes of transport particularly walking and cycling. The details of the site observations and the corresponding calculations together with critical comparative analysis and relevant conclusions will be reported in the full version of the paper.

Keywords: noise calculation, noise field measurement, road traffic noise, speed limit in london, survey of people satisfaction

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292 Designing Short-Term Study Abroad Programs for Graduate Students: The Case of Morocco

Authors: Elaine Crable, Amit Sen

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Short-term study abroad programs have become a mainstay of MBA programs. The benefits of international business experiences, along with its exposure to global cultures, are well documented. However, developing a rewarding study, abroad program at the graduate level can be challenging for Faculty, especially when devising such a program for a group of part-time MBA students who come with a wide range of experiences and demographic characteristics. Each student has individual expectations for the study abroad experience. This study provides suggestions and considerations for Faculty that are planning to design a short-term study abroad program, especially for part-time MBA students. Insights are based on a recent experience leading a group of twenty-one students on a ten-day program to Morocco. The trip was designed and facilitated by two faculty members and a local Moroccan facilitator. This experience led to a number of insights and recommendations. First, the choice of location is critical. The choice of Morocco was very deliberate, owing to its multi-faceted cultural landscape and international business interest. It is an Islamic State with close ties to Europe both culturally and geographically and Morocco is a multi-lingual country with some combination of three languages spoken by most – English, Arabic, and French. Second, collaboration with a local ‘academic’ partner allowed the level of instruction to be both rigorous and significantly more engaging. Third, allowing students to participate in the planning of the trip enabled the trip participants to collaborate, negotiate, and share their own experiences and strengths. The pre-trip engagement was structured by creating four sub-groups, each responsible for an assigned city. Each student sub-group had to provide a historical background of the assigned city, plan the itinerary including sites to visit, cuisine to experience, industries to explore, markets to visit, plus provide a budget for that city’s expenses. The pre-planning segment of the course was critical for the success of the program as students were able to contribute to the design of the program through collaboration and negotiation with their peers. Fourth, each student sub-group was assigned industry to study within Morocco. The student sub-group prepared a presentation and a group paper with their analysis of the chosen industries. The pre-planning activities created strong bonds among the trip participants, which was evident when faced with on-ground challenges, especially when it was necessary to quickly evacuate due to a surprise USA COVID evacuation notice. The entire group supported each other when quickly making their way back to the United States. Unfortunately, the trip was cut short by two days due to this emergency exit, but the feedback regarding the program was very positive all around. While the program design put pressure on the Faculty leads regarding planning and coordination upfront, the outcome in terms of student engagement, student learning, collaboration and negotiation were all favorable and worth the effort. Finally, an added value, the cost of the program for the student was significantly lower compared to running a program with a professional provider.

Keywords: business education, experiential learning, international education, study abroad

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291 Promoting Incubation Support to Youth Led Enterprises: A Case Study from Bangladesh to Eradicate Hazardous Child Labour through Microfinance

Authors: Md Maruf Hossain Koli

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The issue of child labor is enormous and cannot be ignored in Bangladesh. The problem of child exploitation is a socio-economic reality of Bangladesh. This paper will indicate the causes, consequences, and possibilities of using microfinance as remedies of hazardous child labor in Bangladesh. Poverty is one of the main reasons for children to become child laborers. It is an indication of economic vulnerability, inadequate law, and enforcement system and cultural and social inequities along with the inaccessible and low-quality educational system. An attempt will be made in this paper to explore and analyze child labor scenario in Bangladesh and will explain holistic intervention of BRAC, the largest nongovernmental organization in the world to address child labor through promoting incubation support to youth-led enterprises. A combination of research methods were used to write this paper. These include non-reactive observation in the form of literature review, desk studies as well as reactive observation like site visits and, semi-structured interviews. Hazardous Child labor is a multi-dimensional and complex issue. This paper was guided by the answer following research questions to better understand the current context of hazardous child labor in Bangladesh, especially in Dhaka city. The author attempted to figure out why child labor should be considered as a development issue? Further, it also encountered why child labor in Bangladesh is not being reduced at an expected pace? And finally what could be a sustainable solution to eradicate this situation. One of the most challenging characteristics of child labor is that it interrupts a child’s education and cognitive development hence limiting the building of human capital and fostering intergenerational reproduction of poverty and social exclusion. Children who are working full-time and do not attend school, cannot develop the necessary skills. This leads them and their future generation to remain in poor socio-economic condition as they do not get a better paying job. The vicious cycle of poverty will be reproduced and will slow down sustainable development. The outcome of the research suggests that most of the parents send their children to work to help them to increase family income. In addition, most of the youth engaged in hazardous work want to get training, mentoring and easy access to finance to start their own business. The intervention of BRAC that includes classroom and on the job training, tailored mentoring, health support, access to microfinance and insurance help them to establish startup. This intervention is working in developing business and management capacity through public-private partnerships and technical consulting. Supporting entrepreneurs, improving working conditions with micro, small and medium enterprises and strengthening value chains focusing on youth and children engaged with hazardous child labor.

Keywords: child labour, enterprise development, microfinance, youth entrepreneurship

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290 Exploring Valproic Acid (VPA) Analogues Interactions with HDAC8 Involved in VPA Mediated Teratogenicity: A Toxicoinformatics Analysis

Authors: Sakshi Piplani, Ajit Kumar

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Valproic acid (VPA) is the first synthetic therapeutic agent used to treat epileptic disorders, which account for affecting nearly 1% world population. Teratogenicity caused by VPA has prompted the search for next generation drug with better efficacy and lower side effects. Recent studies have posed HDAC8 as direct target of VPA that causes the teratogenic effect in foetus. We have employed molecular dynamics (MD) and docking simulations to understand the binding mode of VPA and their analogues onto HDAC8. A total of twenty 3D-structures of human HDAC8 isoforms were selected using BLAST-P search against PDB. Multiple sequence alignment was carried out using ClustalW and PDB-3F07 having least missing and mutated regions was selected for study. The missing residues of loop region were constructed using MODELLER and energy was minimized. A set of 216 structural analogues (>90% identity) of VPA were obtained from Pubchem and ZINC database and their energy was optimized with Chemsketch software using 3-D CHARMM-type force field. Four major neurotransmitters (GABAt, SSADH, α-KGDH, GAD) involved in anticonvulsant activity were docked with VPA and its analogues. Out of 216 analogues, 75 were selected on the basis of lower binding energy and inhibition constant as compared to VPA, thus predicted to have anti-convulsant activity. Selected hHDAC8 structure was then subjected to MD Simulation using licenced version YASARA with AMBER99SB force field. The structure was solvated in rectangular box of TIP3P. The simulation was carried out with periodic boundary conditions and electrostatic interactions and treated with Particle mesh Ewald algorithm. pH of system was set to 7.4, temperature 323K and pressure 1atm respectively. Simulation snapshots were stored every 25ps. The MD simulation was carried out for 20ns and pdb file of HDAC8 structure was saved every 2ns. The structures were analysed using castP and UCSF Chimera and most stabilized structure (20ns) was used for docking study. Molecular docking of 75 selected VPA-analogues with PDB-3F07 was performed using AUTODOCK4.2.6. Lamarckian Genetic Algorithm was used to generate conformations of docked ligand and structure. The docking study revealed that VPA and its analogues have more affinity towards ‘hydrophobic active site channel’, due to its hydrophobic properties and allows VPA and their analogues to take part in van der Waal interactions with TYR24, HIS42, VAL41, TYR20, SER138, TRP137 while TRP137 and SER138 showed hydrogen bonding interaction with VPA-analogues. 14 analogues showed better binding affinity than VPA. ADMET SAR server was used to predict the ADMET properties of selected VPA analogues for predicting their druggability. On the basis of ADMET screening, 09 molecules were selected and are being used for in-vivo evaluation using Danio rerio model.

Keywords: HDAC8, docking, molecular dynamics simulation, valproic acid

Procedia PDF Downloads 248